issn 0972-0200 vol.22, no.4, april - june, 2011 delhi ... · 295. pharmacologic treatment of...

Delhi Journal of Ophthalmology

Vol. 22, No.4, April - June, 2012 [email protected] 243

ISSN 0972-0200 Vol.22, No.4, April - June, 2011

Editor-in- Chief

Associate EditorManaging Editor

Advisory Board

Editorial Board

Rajesh Sinha

Harinder S. Sethi Sumit Khanduja

M.Vanathi

Rajvardhan AzadAshok K. GroverLalit K.VermaYograj SharmaHarbans LalMahipal S. SachdevK.P.S. MalikAtul Kumar Namrata Sharma Rishi Mohan Tanuj Dada Rajinder Khanna Rohit Saxena Sanjiv Mohan Tushar Agarwal

Rasik B. VajpayeeHem K.TiwariB.P.GulianiS.P.GargJeewan S. TitiyalB.GhoshAnita PandaRadhika TandonSudarshan Khokhar Zia ChaudhuriRitu Arora Amit Khosla Neelam Pushkar Ruchi Goel

Saptorishi MajumdarShorya V. AzadRaghav GuptaSangeeta RoyTarun AroraRavi BBhaskar JhaAnasua GangulySubodh SinghKoushik Tripathy

Digvijay SinghVarun Gogia ReetikaSri Vatsa SehraKumar VivekRebika DhimanMayank BansalRajshri Hirawat Manik MittalVishal Arora

Editorial Assistant & Formatting

Editorial Office

Varun Kumar

Dr Rajesh SinhaRoom No. 479, 4th Floor

Dr. R.P. Centre for Ophthalmic Sciences,AIIMS, New Delhi-110029

Ph +91-011-65705229, 26588074 Email : [email protected]

General InformationDelhi Journal of Ophthalmology (DJO), once called Visiscan,

is a quarterly journal brought out by the Delhi Ophthalmological Society. The journal aims at providing a platform to its readers for free exchange of ideas and information in accordance with the rules laid out for such publication. The DJO aims to become an easily readable referenced journal which will provide the specialists with up to date data and the residents with articles providing expert opinions supported with references.

Contribution MethodologyAuthor/Authors must have made significant contribution

in carrying out the work and it should be original. It should be accompanied by a letter of transmittal.The article can be sent by email to the Editor or a hard copy posted. Articles received will be sent to reviewers whose comment will be emailed to the author(s) within 4-6 weeks. The identity of the authors and the reviewers will not be revealed to each other by the editorial team. Detailed instructions to the contributors and for advertisement are included at the end of the journal.

Editorial ProcessThe DJO has Dr Rajesh Sinha as its Editor who is assisted by

a team of renowned ophthalmologists and an illustrous editorial board. The reviewers, who are leaders in their respective fields, form the back bone of the journal by setting standards for the published work.

DisclaimerThe journal does not take any responsibility for the articles

published in the journal unless it is explicitly stated so. The views expressed in the articles and editorials are of the authors and do not in any way reflect the policy of the Delhi Journal of Ophthalmology. The journal does not endorse or guarantee the quality or efficacy of any product or service mentioned or advertised in the journal issues. Advertisements carried in this journal are expected to conform to internationally accepted medical, ethical and business standards.

Published by Dr Rajesh Sinha, Editor DJO,Delhi Ophthalmological Society


Cover Page Designed By Amit Chauhan



247. Editorial ........Dr. Rajesh Sinha

Contents

249. Thyroid Associated Ophthalmopathy Sonam Angmo Bodh, Saurabh Kamal, Ruchi Goel, Sushil Kumar, Smriti Bansal, Madhu Singh

257. Dysfunctional Tear Syndrome: Some New Perspectives Punit K Singh

Major Review

263. Comparative evaluation of the antiinflammatory effect of topical 0.1% dexamethasone sodium and topical 1% prednisolone acetate eye drops after small incision cataract surgery in Indian eyes Somen Misra, Sulbha Gaydhankar, Rajen Mehta

269. Combined Surgery, Cryotherapy and Topical 0.002% Mitomycin C for Primary and Recurrent Corneal Conjunctival Intraepithelial Neoplasia: A Long - Term Follow Up Saroj Gupta, RK Gupta

Original Article

275. Minimal Duration Cataract Surgery (MDCS) - SICS without Superior rectus stitch, no conjunctival flap and no cauterization Ram Lal Sharma, Praveen Panwar

Techniques

281. Canalicular Dacryolithiasis Shakeen Singh, Rubina Tuli Soni, Vyankatesh Aironi, Baljeet Singh Dhillon

287. Atypical Presentation of Primary Non-Hodgkin Lymphoma of the Lacrimal Gland Bhavna Chawla, Seema Kashyap, Sanjay Sharma, Mandeep S. Bajaj, Neelam Pushker, Mahesh Chandra, Supriyo Ghose

285. Ocular Myocysticercosis : An Unusual Cause of Ptosis with Involvement Levator Palpebrae Superioris & Superior Rectus Muscle Kirti jain, KPS Malik, VK Malik, Charu Jain

Case Report

289. Retreatment of Magnetically Treated Giant Retinal Tear Rhibhu Soni, Rubina T Soni, Preetam Singh,Vipin K Vig, Rajbir Singh

Contents (Contd.........)

Vol. 22, No. 4, April - June, 2012246


311. Epithelial Tumors of Lacrimal Gland - Management Pearls Ruchi Goel, Saurabh Kamal, Sonam Angmo Bodh, Sushil Kumar, Smriti Nagpal, Ksitij Aditya, Smriti Bansal, Puja Sakhuja

Photo Essay

313. HOYA iTrace “Preloaded iMICS1 lenses (251 & 250 model)”

Industry News

Information to Author

301. The Impact of Promoting Awareness, Screening and Patient Education Programs on the Treatment and Follow up of Glaucoma Patients Attending a Tertiary eye hospital in Nepal Suman S. Thapa

Allied Ophthalmic Sciences : Community Ophthalmology

Copy Right Form

305. A Unusual Case of Self Inflicted Multiple Needles Injuries to both eyes Shweta Gaur, HK Bisht

307. Letter to editor Mayank Bansal

Brief Communication

Recent Advances

295. Pharmacologic Treatment of Atrophic Age Related Macular Degeneration: An update Raghav Gupta, Shorya Azad, Abhishek Dave, Harsh Inder Singh



“One machine can do the work of fifty ordinary men. No machine can do the work of one extraordinary man.”

Elbert Hubbard

Over the years, man has come up with countless inventions, each more

resourceful than the last. However, as the computer age continues,

mankind is threatened. With invent of the femtocataract surgery, the

same question ponders each mind. “Will we have no role in future

cataract surgery then to press buttons of a machine, while it does all

work for us?”

The human brain has a lot of flaws, yet it also has an edge over the computer. It has the capacity to create,

unlike the computer, and it can work without full input, making logical assumptions about problems. A person

can work with a wide variety of methods, seeing new, more efficient ways of handling problems. It can come

up with infinite ways of getting around problems encountered in a surgery, while a computer has a limited

memory of new tricks it can come up with, limited by its programming. Till the time humans possess the

unique power to control these high tech machines technology will be there for the good of mankind.

Can these machines ever procure “reason and virtue”, or are they simply calculators on steroids? We have

now reached the point where we must redefine what constitutes reason in the 21st century.

Rajesh SinhaMD, DNB, FIACLE, FRCS

Editorial



Thyroid Associated Ophthalmopathy

Abstract Thyroid associated orbitopathy/ophthalmopathy is an autoimmune disorder. It is most prevalent among females and

is usually associated with thyroid dysfunction. Clinical manifestations include soft tissue signs, lid retraction, lid lag, proptosis, restrictive myopathy, corneal exposure and optic neuropathy. Thyroid function tests, thyroid antibodies and imaging to demonstrate extraocular muscle enlargement aid diagnosis. Treatment involves correction of thyroid dysfunction, supportive therapy, immunosuppression for moderate to severe active disease and orbital decompression surgery.

Del J Ophthalmol 2012;22(4):249-255. Key Words: lid retraction, lid lag, globe lag, proptosis, orbital decompression.

Sonam Angmo Bodh MS, DNB, Saurabh Kamal MS, DNB, Ruchi Goel MS, DNB,Sushil Kumar MS, Smriti Bansal MBBS, Madhu Singh MBBS

Guru Nanak Eye Centre, Maulana Azad Medical College

Correspondence to : Dr. Sonam Angmo BodhE-Mail : [email protected]

Major Review

Graves’ orbitopathy/ophthalmopathy (GO) also known as thyroid eye disease (TED), dysthyroid/thyroid-associated ophthalmopathy (TAO), is an autoimmune disorder representing the commonest and most important extrathyroidal manifestation of Graves’ disease, but it may occur in patients without current or prior hyperthyroidism (euthyroid or ophthalmic Graves’ disease) or in patients who are hypothyroid due to chronic autoimmune (Hashimoto’s) thyroiditis.1,2 Clinical symptoms and signs are usually mild, consisting of ocular irritation with redness and tearing, stare due to lid retraction and exophthalmos, and periorbital swelling. Approximately 28% of GO cases are severe, with restricted motility leading to diplopia, exposure keratopathy, and optic neuropathy.3,4 Patients with severe GO may have lower rates of remission of their thyroid disease compared to mild GO patients.5

EpidemiologyGraves’ disease is a common disorder with an annual

incidence in women of one per 1,000 population. In addition to hyperthyroidism, clinical involvement of the eyes develops in 25% to 50% of individuals with Graves disease.6 The annual incidence of Graves ophthalmopathy in women is approximately 16 in 100,000 and in men 3 in 100,000. There appears to be a female preponderance in which women are affected 2.5-6 times more frequently than men; however, severe cases occur more often in men than in women. In addition, most patients are aged 30-50 years, with severe cases appearing to be more frequent in those older than 50 years. It is the most common cause of bilateral exophthalmos, accounting for ~ 85% of cases.7 GO also presents as unilateral exophthalmos, accounting for 15-28% of cases.8,9 Although many patients are thought

to have unilateral disease on the basis of clinical findings, radiographic evidence of bilateral disease is present in a majority.10,11 Cigarette smoking has been considered the strongest risk factor for developing GO.12,13 The studies have shown that among patients with GO, smokers have more severe eye disease.14,15

PathophysiologyThe underlying pathophysiology is thought to be

an antibody-mediated reaction against the TSH receptor with orbital fibroblast modulation of T- cell lymphocytes. The T-cell lymphocytes are believed to react against thyroid follicular cells with shared antigenic epitopes in the retrobulbar space.16 The lymphocytic infiltration leads to the activation of cytokine networks and inflammation and interstitial edema of the extraocular muscles.17 Excess secretion of glycosaminoglycans by orbital fibroblasts seems to be an important contributor. The end result is expansion of the volume of extraocular muscles, retrobulbar fat and connective tissue. Similar changes affect the eyelids and anterior periorbital tissues.18

Clinical FeaturesThe eye manifestations of Graves ophthalmology

typically are self-limited. An active phase of inflammation and progression tends to stabilize spontaneously within 3-5 years of onset.19 Initial symptoms of Graves' ophthalmology may be complaints of foreign-body sensation, tearing, or photophobia. Periorbital inflammation often predominates early in the disease course. The most characteristic signs (table 1) are eyelid erythema and swelling, caruncular and conjunctival injection, and edema.3,20 Fluctuating upper or lower eyelid swelling indicates active disease while chronic swelling in the absence of erythema suggests congestive ophthalmopathy. Proptosis and lid retraction with lateral eyelid flare can present during any phase of GO and yield the characteristic staring appearance. Lid retraction, also

Vol. 22, No. 4, April - June, 2012250


known as Dalrymple's sign occurs commonly in 37-92% of patients.21 It may present as an isolated finding or in association with exophthalmos. Upper eyelid retraction may result from increased sympathomimetic tone, but may also be the consequence of eyelid fibrosis.22-25 Retraction of the lower lid usually correlates with the severity of proptosis.26

Conjunctival signs include deep temporal injection. Enlarged vessels may be visible over the insertion of the medial and lateral rectus muscles. Conjunctival chemosis and lid edema may both be present especially in the early, active phase. Conjunctival and caruncle signs usually suggest active disease.27,28 Exophthalmos reflects an increase in soft tissue mass within the bony orbit and may result from enlargement of the extraocular muscles or increased orbital fat volume.18 Exophthalmos is almost always bilateral and usually relatively symmetrical.29 Attempts to push the globe back into the orbit (retropulsion) typically are met with firm resistance because of the inflammatory orbital changes that preclude displacement of the fat. Limitation of ocular motility is the direct consequence of pathological changes that affect the extraocular muscles. The inferior rectus muscle is involved most commonly, followed by the medial rectus and the superior rectus.30 Clinical complaints associated most frequently with muscle restriction are nontorsional, vertical, or oblique diplopia, which may be noticed only on awakening. Motility dysfunction from involvement of the oblique muscles is generally overwhelmed by those of the rectus muscles. It should also be noted that most patients with GO, including those with no evidence of ocular motility abnormalities, exhibit some degree of EOM involvement demonstrable by radiographic techniques.31,32 Intraocular pressure may increase on gaze in the opposite direction of the restricted muscle. In particular, this is seen on upgaze with inferior rectus restriction. Exposure keratitis occurs in patients with GO for several reasons. Inadequate eyelid closure, the consequence of proptosis and eyelid dysfunction, contributes to excessive moisture

loss. Diminished tear production resulting from lacrimal gland infiltration and lagophthalmos from proptosis or loss of Bells phenomenon from inferior rectus infiltration can also complicate management. Visual loss rarely complicates GO and usually results from compressive optic neuropathy. Optic neuropathy occurs in ~ 5% of individuals with GO and affected individuals usually do not exhibit marked proptosis or optic nerve changes under ophthalmoscopic

von Graefe’s sign lid lag in down gaze

Joffroy sign absent creases in the forehead on superior gaze

Grove sign resistance to pulling down the retracted upper lid

Stellwag sign incomplete and infrequent blinking

Boston sign Jerky irregular movement on downgaze

Vigouroux sign eyelid fullness

Dalrymple's sign a widened palpebral fissure during fixation

Kocher’s sign eye globe lag in up gaze

Möbius sign poor convergence

Ballet sign restriction of one or more extraocular muscles

Gifford sign Difficulty in everting upper lid

Griffith sign Lower lid lag on downgaze

Jellink’s sign Increased pigmentation on the lids

TABLE 1. Numerous eponymous signs associated with Grave’s orbitopathy

Class Grade

0 No signs or Symptoms1 Only Signs

2 0ABC

Soft tissue involvement, with symptoms and signAbsent

MinimalModerate

Marked

30ABC

Proptosis<23mm

23-24mm25-27mm≥28mm

40ABC

Extraocular muscle involvementAbsent

Limitation of motion in extremes of gazeEvident restriction of movement

Fixed eyeball

50ABC

Corneal involvementAbsent

Stippling of corneaUlcerationClouding

60ABC

Sight lossAbsent

20/20 – 20/6020/70 – 20/200

<20/200

TABLE 2. NO SPECS Classification



examination.33 Risk factors for optic neuropathy include older age, smoking, male gender, and significant strabismus with mild proptosis.12,14

Risk factors of progressive and severe thyroid-associated orbitopathy:-a Age greater than 50 years

a Rapid onset of symptoms under 3 months

a Cigarette smoking

a Diabetes

a Severe or uncontrolled hyperthyroidism

a Presence of pretibial myxedema

a High cholesterol levels (hyperlipidemia)

a Peripheral vascular disease

Classification for Grave’s OrbitopathyThe simplest classification for thyroid-associated

orbitopathy is type I and type II.16

Type I is characterized by minimal inflammation and restrictive myopathy.

Type II is characterized by significant orbital inflammation and restrictive myopathy.

In 1969, Werner proposed the “NO SPECS” classification for signs of GO (Table 2).34 In 1981, Van Dyke refined the class 2 NO SPECS soft tissue findings with the mnemonic RELIEF (Table 3).35 Unfortunately, the NO SPECS classification has some weaknesses that may limit its prognostic value. Patients may fall into more than one particular class, and they may not progress in an orderly fashion from class 1 to class 6. In addition, patients with visual loss from compressive optic neuropathy may not show marked

proptosis or other signs of severe disease. Thus, it has been abandoned. Other systems have been proposed, but none is well-standardized.27,28 The most widely utilized of these is an activity scale (CAS) first described by Mourits and colleagues.27,28 It attempts to identify patients with active disease who are likely to respond to medical therapy. Each symptom or sign is assigned equal weight; the score is a simple summation. A score of 4 or more points has been reported to accurately predict antiinflammatory effects (Table 4).

Diagnosis• Graves' ophthalmopathy17 is diagnosed clinically by the

presenting ocular signs and symptoms, but positive tests for antibodies (anti-thyroglobulin, anti-microsomal and anti-thyrotropin receptor) and abnormalities in thyroid hormones level (T3, T4 and TSH) help in supporting the diagnosis.

• Orbital ultrasound can confirm if the patient has thickened muscles or an enlarged superior ophthalmic vein.

• Neuroimaging usually reveals thick muscles with tendon sparing.

• Neuroimaging may show a dilated superior ophthalmic vein and apical crowding of the optic nerve.

Resistance to retropulsion

Edema of conjunctiva and caruncle

Lacrimal gland enlargement

Injection over the horizontal rectus muscle insertions

Edema of the eyelids

Fullness of the eyelids

TABLE 3. RELIEF Classification of soft tissue signs and symptoms

Pain• Painful,oppressivefeelingonorbehindtheglobeduringthelast2weeks• Painonattemptedup,sideordowngazeduringthelast4weeks

Redness • Rednessoftheeyelids• Diffuserednessoftheconjunctivacoveringatleastonequadrant

Swelling

• Swellingoftheeyelids• Chemosis• Swollencaruncle• Increaseofproptosis≥2mmduringaperiodof1-3months

Impaired Function

• Decreaseofeyemovementsinanydirection≥5°duringaperiodof1-3months• Decreaseofvisualacuityof≥1lineontheSnellenchartduringaperiodof1-3months

TABLE 4. Activity measures based on the classical features of inflammationclinical activity score is the sum of all items present

Vol. 22, No. 4, April - June, 2012252


• MRI is more sensitive for showing optic nerve. CT scan is performed prior to bony decompression because it shows better bony architecture. Occasionally the proptosis results in straightening of the optic nerve.

• Histological findings

o Lymphocytic cell infiltration

o Enlargement of fibroblasts

o Accumulation of mucopolysaccharides

o Interstitial oedema

o Increased collagen production

o Fibrosis with degenerative changes in the eye muscles

Management• All patients with Graves’ disease should be informed

of the risks of smoking for GO emphasizing the detrimental effects of smoking on

t Development of GO

t Deterioration of pre-existing GO

t Effectiveness of treatments for GO

t Progression of GO after radioiodine treatment

• Treatment of thyroid gland dysfunction

t Euthyroidism should be restored promptly and maintained stably in all patients.

t Frequent monitoring of thyroid status (every 4–6 weeks) is imperative in the initial phases of treatment when changes in thyroid status are expected.

t Patients with active GO given radioiodine should be offered prophylactic steroid cover (commencing with

0.3–0.5 mg of prednisone/kg of body weight per day orally 1–3 days after radioiodine and tapering the dose until withdrawal ~ 3 months later)

t Shorter periods of steroid therapy (1–2 months) may be equally protective.

t Patients with inactive GO can safely receive radioiodine without steroid cover as long as hypothyroidism is avoided particularly if other risk factors for GO progression, such as smoking, are absent.

• Treatment of ophthalmopathy

1. Supportive measures

t Lubricant eye drops during the day and/or lubricant ointments at night-time, cool compresses, and head elevation when sleeping.37

t Patients with symptomatic diplopia should be given prisms if appropriate.

t Topical adrenergic blocking agents such as 5% guanethidine sulfate drops transiently improve mild eyelid retraction, they are not widely used due to side effects of worsened ocular redness and pain.38 Botulinum toxin injection may be considered for upper lid retraction.

2. Medical management

t Steroids: Systemic steroids are usually reserved for patients with severe inflammation or compressive optic neuropathy in GO. The consensus statement of the European Group on Graves' orbitopathy suggests intravenous glucocorticoids for patients with advanced thyroid-associated orbitopathy.38 Steroids may decrease the production of mucopolysaccharides by the fibroblasts. Intravenous glucocorticoids seem to be associated with higher success rate and better tolerability as compared to oral glucocorticoids.39

Sight-threatening GOPatients with dysthyroid optic neuropathy (DON) and/or corneal breakdown. This category warrants immediate intervention.

Moderate-to-severe GO

These patients usually have any one or more of the following: lid retraction >2 mm, moderate or severe soft tissue involvement, exophthalmos >3 mm above normal for race and gender, inconstant, or constant diplopia.

Mild GO

These patients usually have only one or more of the following: minor lid retraction (<2 mm), mild soft tissue involvement, exophthalmos <3 mm above normal for race and gender, transient or no diplopia, and corneal exposure responsive to lubricants.

TABLE 5. European Group on Graves’orbitopathy (EUGOGO)36 recommends the following classification of patients with GO



t Radiotherapy: This has a non specific anti- inflammatory effect and destroys the radiosensitive lymphocytes40,41 and reduces glycosaminoglycans production.42-45 Usually a cumulative dose of 20 Gy per eye fractioned in 10 daily doses over a two week period is used. Orbital radiotherapy may cause a transient exacerbation of inflammation, but this can be prevented by concomitant steroid administration.42

t Antioxidants: Treatment with anti oxidants like nicotinamide and allopurinol, has shown encouraging results in mild and moderately severe newly diagnosed active disease.44 Nicotinamide and allopurinol have been used in doses of 300mg daily.43

t Somatostatin analogues: These receptors can be visualized in vivo in orbital tissue of GO patients.45 Somatostatin analogues bind to certain somatostatin receptors on surface of various orbital cells like lymphocytes, fibroblasts and muscle cells, thereby altering their immunologic and metabolic activities.44 Recent studies have shown successful therapy with octreotide and lanreotide in patients with moderately severe GO and a positive Octreoscan.45,46

t Monoclonal antibodies: Rituximab, a chimeric monoclonal antibody, is being evaluated for its possible role in Graves’ ophthalmopathy.47,48 Rituximab causes an immediate depletion of circulating B cells which usually lasts for 4-6 months but may last upto 4 years. T cells and natural killer cells are usually not affected.43

t Immunosuppressive drugs: The autoimmune origin of GO has prompted the use of immunosuppressive drugs however their efficacy is yet to be proven. Cyclosporine has a lower effectiveness than glucocorticoids but a combination may be more effective than either treatment alone.42 Low dose treatment with methotrexate is being used with apparent success.49 Other drugs that have been tried include azathioprine and cyclophosphamide.50 However these drugs are yet to prove their efficacy.

3. Surgical management

Surgical treatment of Graves' ophthalmopathy includes decompression of the orbit, strabismus surgery, and eyelid retraction repair.

t Orbital decompression: Surgical decompression creates more space for the swollen tissues by expanding the walls of the orbit (bony decompression) or by removing excess orbital fat (fat decompression). The primary indications for orbital decompression are compressive optic neuropathy and excessive proptosis. The many approaches to orbital bony decompression can be categorized based on the surgical approach to the orbit (transantral, lateral, transfrontal/coronal, transconjunctival, transcaruncular, endoscopic transnasal), or on the number of bony walls removed (one, two, three, or four wall). A one-

wall decompression typically yields 0-4 mm proptosis reduction, a two-wall decompression 3-7 mm, a three-wall decompression 6-10 mm, and a four-wall decompression 10-17 mm.51,52 The air-filled spaces of the ethmoid and maxillary sinuses generally offer the best opportunities for greatest volume expansion, although the temporal fossa and deep lateral bony orbit can provide significant space; the orbital roof generally provides the smallest area for decompression.

When decompression is performed for optic neuropathy, a medial wall decompression generally allows the most direct access to the orbital apex. A medial decompression can be combined quite readily with a orbital floor decompression to increase the volume of decompression. Generally, it is necessary only to remove the medial orbit floor, stopping at the infraorbital neurovascular bundle and extending to a depth of 3.5 cm posteriorly. A three-wall decompression of the medial and lateral orbit and the orbital floor can be achieved by an endoscopic transnasal decompression with a lid crease-based lateral decompression. Alternatively, a bicoronal approach can permit access to the three walls.51,53,54

The orbit can also be decompressed by orbital fat removal, either in conjunction with bony decompression or as a stand-alone procedure. Orbital fat decompression has been reported to reduce proptosis by 2 mm on average, although reductions of 6 mm or more can be achieved in some patients.55

t Strabismus surgery: Strabismus surgery generally is delayed until ophthalmopathy is inactive and the prism measurements have been stable for a minimum of 6 months. Strabismus surgery predominantly involves recessions rather than resections because of the presence of restrictive myopathy. Adjustable suture surgery is recommended in all possible cases.

t Eyelid retraction surgery: Lid-lengthening surgery should be considered if restoration of the euthyroid state does not improve lid retraction. Corneal exposure is reduced by this surgery which helps in camouflaging mild-to-moderate proptosis. A muller muscle excision can be used to ameliorate a 2 to 3 mm upper lid retraction. The temporal flare may be reduced by employing lateral levator tenotomy. For further lid recession, levator recession is a good option.

Summary Graves’ orbitopathy is an autoimmune disorder

with clinical signs which are characteristic and include a combination of eye lid retraction, lid lag, globe lag, proptosis, restrictive extraocular myopathy and optic neuropathy. Diagnosis is confirmed on various clinical signs and studies like ultrasonography, CT scan and MRI. Various pharmacotherapy and surgical options are available depending on the various stages of orbitopathy.

Vol. 22, No. 4, April - June, 2012254


References

1. Bartalena L, Pinchera A, Marcocci C. Management of Graves’ ophthalmopathy: reality and perspectives. Endocrine Reviews 2000; 21:168–99.

2. Perros P, Dickinson AJ. Ophthalmopathy. In Werner’s and Ingbar’s The Thyroid – A Fundamental and Clinical Text, edn 9,pp 474–487. Eds. LE Braverman & RD Utiger, Philadelphia:Lippincott Williams & Wilkins, 2005.

3. Prummel M, Bakker A, Wiersinga W, et al. Multi-center study on the characteristics and treatment strategies of patients with Graves’ orbitopathy: the first European Group on Graves’ Orbitopathy experience. Eur J Endocrinol 2003; 148:491–5.

4. Schotthoefer EO, Wallace DK. Strabismus associated with thyroid eye disease. Curr Opin Ophthalmol 2007; 18:361–5.

5. Eckstein AK, Lax H, Losch C, et al. Patients with severe Graves’ ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission. Clin Endocrinol 2007; 67:607–12.

6. Garrity JA, Bahn RS. Pathogenesis of Graves Ophthalmopathy: Implications for Prediction, Prevention, and Treatment. American Journal of Ophthalmology 2006; 147-153.

7. Rootman J. Inflammatory diseases of the orbit. Highlights. J Fr Ophtalmol 2001; 24:155-61.

8. Grove Jr AS, Evaluation of exophthalmos. N Engl J Med 1975; 292:1005-13.

9. Lawton NF. Exclusion of dysthyroid eye disease as a cause of unilateral proptosis. Trans Ophthalmol Soc UK 1979; 99:226-8.

10. Wende S, Aulich A, Nover A, et al. Computed tomography or orbital lesions. A cooperative study of 210 cases. Neuroradiology 1977; 13:123-34.

11. Villadolid MC, Yokoyama N, Izumi M, et al. Untreated Graves’ disease patients without clinical ophthalmopathy demonstrate a high frequency of extraocular muscle enlargement by magnetic resonance. J Clin Endocrinol Metab 1995; 80:2830-33.

12. Bartalena L: Smoking and Graves’ disease. J Endocrinol Invest 2002;25(2):152-7.

13. Bartalena L, Bogazzi F, Tanda ML, et al. Cigarette smoking and the thyroid. Eur J Endocrinol 1995; 133:507-12.

14. Bartalena L, Marcocci C, Tanda ML, et al. Cigarette smoking and treatment outcomes in Graves ophthalmopathy. Ann Intern Med 1998; 129:632-5.

15. Eckstein A, Quadbeck B, Mueller G, et al. Impact of smoking on the response to treatment of thyroid associated ophthalmopathy. Br J Ophthalmol 2003; 87:773-6.

16. Ing E, Abuhaleeqa K. Graves’ Ophthalmopathy (thyroid-associated orbitopathy). Clinical and Surgical Ophthalmology 2007; 25:386-92

17. Boboridis K, Perros P. General management plan. In: Weirsinga WM, Kahaly GJ, eds. Graves’ Ophthalmopathy: A multidisciplinary approach. Basel: Karger 2008:88-95.

18. Perros P, Neoh C, Dickinson J. Thyroid Eye Disease: Clinical review. BMJ 2009;338:b560.

19. Bartley GB, Fatourechi V, Kadrmas EF, et al. Long-term follow-up of Graves ophthalmopathy in an incidence cohort. Ophthalmology 1996; 103:958-62.

20. Prummel MF. Pathogenetic and clinical aspects of endocrine ophthalmopathy. Exp Clin Endocrinol Diabetes 1999.575-8.

21. Konuk EB, Konuk O, et al. Expression of cyclogenase-2 in orbital fibroadipose connective tissues of Graves’ Ophthalmopathy Patients. Eur J Endocrinol 2006; 155:681-5.

22. Cockerham KP, Hidayat AA, Brown HG, et al. Clinicopathologic evaluation of the Mueller muscle in thyroid-associated orbitopathy. Ophthal Plast Recon Surg 2002; 18:11-7.

23. Cruz AA, Akaishi PM, Coelho RP. Quantitative comparison between upper eyelid retraction induced voluntarily and by Graves orbitopathy. Ophthal Plast Reconstr Surg 2003; 19:212-15.

24. Esmaeli-Gutstein B, Hewlett BR, Pashby RC, et al. Distribution of adrenergic receptor subtypes in the retractor muscles of the upper eyelid. Ophthal Plast Recon Surg 1999; 15:92-9.

25. Hamada N, Okamoto Y, Yoshida H, et al. Sympathetic overactivity in the development of eyelid retraction in a patient with euthyroid Graves’ disease evaluated by accommodation. Endocr J 2000; 47:623-8.

26. van den Bosch WA, Tjon-Fo-Sang MJ, Lemij HG. Eyeball position in Graves orbitopathy and its significance for eyelid surgery. Ophthal Plast Recon Surg 1998; 14:328-35.

27. Mourits MP, Koornneef L, Wiersinga WM, et al. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: a novel approach. Br J Ophthalmol 1989; 73:639-44

28. Mourits MP, Prummel MF, Wiersinga WM, Koornneef L. Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clin Endocrinol (Oxf) 1997; 47:9-14.

29. Kamminga N, Jansonius NM, Pott JW, Links TP. Unilateral proptosis: the role of medical history. Br J Ophthalmol 2003; 87:370-1.

30. Murakami Y, Kanamoto T, Tuboi T, et al. Evaluation of extraocular muscle enlargement in dysthyroid ophthalmopathy. Jpn J Ophthalmol 2001; 45:622-7.

31. Aydin K, Guven K, Sencer S, et al. A new MRI method for the quantitative evaluation of extraocular muscle size in thyroid ophthalmopathy. Neuroradiology 2003; 45:184-7.

32. Firbank MJ, Coulthard A. Evaluation of a technique for estimation of extraocular muscle volume using 2D MRI. Br J Radiol 2000; 73:1282-9

33. Giaconi JA, Kazim M, Rho T, Pfaff C. CT scan evidence of dysthyroid optic neuropathy. Ophthal Plast Reconstr

AcknowledgementsWe have not received any public or private support

in the preparation of the paper. This paper does not serve the financial or proprietary interests of any individuals or institutions.



Surg 2002; 18:177-82.34. Werner SC. Classification of the eye changes of Graves’

disease. Am J Ophthalmol 1969;68:646-8.35. Van Dyk H J. Orbital Graves’ disease. A modification

of the “NO SPECS” classification. Ophthalmology 1981; 88:479-83.

36. Luigi Bartalena, Lelio Baldeschi1, Alison Dickinson et al Consensus statement of the European Group on Grave’s orbitopathy (EUGOGO) on management of GO. European Journal of Endocrinology 2008; 158:273–85.

37. Gorman CA. Temporal relationship between onset of Graves’ ophthalmopathy and diagnosis of thyrotoxicosis. Mayo Clin Proc 1983; 58:515-9.

38. Perros P, Crombie AL, Kendall-Taylor P. Natural history of thyroid associated ophthalmopathy. Clin Endocrinol (Oxf) 1995; 42:45-50.

39. Wiersinga WM, Prummel MF. Graves’ ophthalmopathy: a rational approach to treatment. Trends Endocrinol Metab 2002; 13:280-7.

40. Paridaens D, et al. The Effect of Etanercept on Grave’s Ophthalmopathy: a pilot study. Eye (Lond) 2005; 19:1286-9.

41. Krassas GE, Heufelder AE. Immunosuppressive therapy in patients with thyroid eye disease: an overview of current concepts. Eur J Endocrinol 2001; 144:311-18.

42. Marcocci C, Marino M, Rochi R, et al. Novel aspects of immunosuppressive and radiotherapy management of Grave’s ophthalmopathy. J Endocrinol Invest 2004; 27:272-80.

43. Boye J, Elter T, Engert T, et al. An overview of the current clinical use of anti Cd20 monoclonal antibody ritumiximab. Ann Oncol 2003; 14:520-35.

44. Bouzas EA, Karadimas P, Mastorakos G, et al. Antioxidant agents in the treatment of Graves’ ophthalmopathy. Am J Ophthalmol 2000; 129:618-22.

45. Krassas KE, Dumas A, Pontikides N, et al. Somatostatin receptor scintigraphy and octreotide treatment in patients with thyroid eye disease. Clin Endocrinol (oxf) 1995; 42:571-80.

46. Kung AVC, Michon J, Tai KS, et al. The effect of somatostatin versus corticosteroids in the treatment of Graves’ ophthalmopathy. Thyroid 1996; 6:381-4.

47. Bartalena L, Tanda L. Immunotherapy for Graves’ orbitopathy: easy enthusiasm but let’s keep trying. J Endocrinol Invest 2006; 29:1012-6.

48. Nielsen Ch, El Fassi D, Hasselbalch HC, et al. B-cell depletion with rituximab in the treatment of autoimmune diseases. Grave’s ophthalmopathy the latest addition to an expanding family. Expert Opin Biol Ther 2007; 7:1061-78.

49. Tanikawa T, Okada Y, Tanaka Y. Intravenous cyclophosphamide pulse therapy is effective for refactory Graves’ ophthalmopathy. J Uoeh 2006; 28:185-91.

50. Durrani K, Papaliodis GN, Foster CS. Pulse IV cyclophosphamide in ocular inflammatory disease. Ophthalmology 2004; 111:960-5.

51. Baldeschi L, MacAndie K, Hintschich C, et al. The removal of the deep lateral wall in orbital decompression: its contribution to exophthalmos reduction and influence on consecutive diplopia. Am J Ophthalmol 2005; 140:642-7.

52. Tallstedt L, Papatziamos G, Lundblad L, Anggard A. Results of transantral orbital decompression in patients with thyroid-associated ophthalmopathy. Acta Ophthalmol Scand 2000; 78:206-10.

53. McCann JD, Goldberg RA, Anderson RL, et al. Medial wall decompression for optic neuropathy but lateral wall decompression with fat removal for non vision-threatening indications. Am J Ophthalmol 2006; 141:916-7.

54. Liao SL, Chang TC, Lin LL: Transcaruncular orbital decompression. an alternate procedure for Graves ophthalmopathy with compressive optic neuropathy. Am J Ophthalmol 2006; 141:810-8.

55. Kazim M, Trokel SL, Acaroglu G, Elliott A. Reversal of dysthyroid optic neuropathy following orbital fat decompression. Br J Ophthalmol 2000; 84:600-5.



Major Review

Dysfunctional Tear Syndrome: Some New Perspectives

Abstract The term “Dysfunctional Tear Syndrome” is a better way to indicate the complex pathological condition

which has been inappropriately referred to as “Dry Eye”. Dysfunctional Tear Syndrome can lead to a chronic inflammatory status with progression of the pathologic erosive changes of the cornea and the conjunctiva. Aging is one of the most common causes of dry eye. About half of all people who wear contact lenses complain of dry eye. Dry eye also occurs or gets worse after LASIK. There are different dry eye severity levels that merit consideration. There are various treatment options available that can be considered.

Del J Ophthalmol 2012;22(4):257-262. Key Words: dysfunctional tear syndrome, kerato conjunctivitis sicca (KCS)

Punit K Singh MS

Dr S N Medical college, Jodhpur (Raj), India

Correspondence to : Dr. Punit K. SinghE-Mail : [email protected]

Dry eye syndrome is one of the most common problems treated by eye physicians. It is usually caused by a problem with the quality of the tear film that lubricates the eyes.1

Dry eye has a significant impact on quality of life. Given the high prevalence and impact on vision-related quality of life, the humanistic burden related to dry eye can be great. In addition, there may be significant economic costs associated with dry eye disease and its care. Patients with dry eye incur direct costs of seeing their ophthalmologists and treatment, as well as the indirect costs of missed work days and decreased functioning. To date, pharmacologic and surgical therapies have been identified as the most costly. With the projection of greater life expectancy, as well as shifting demographics, it is reasonable to predict an increase in the number of patients with dry eye who will need or seek eye care. Given these considerations, it is important to examine the current process of care as it relates to dry eye and to determine if appropriate care is being provided to patients with dry eye disease. Now we evaluate dry eye with respect to history, physical examination, management and patient education.

Tears are comprised of three layers.2,3,4 The mucus layer coats the cornea, the clear outer window of the eye, forming a foundation so the tear film can adhere to the eye. The middle aqueous layer provides moisture and supplies oxygen and other important nutrients to the cornea. This layer is made of 98 percent water along with small amounts of salt, proteins and other compounds. The outer lipid layer is an oily film that seals the tear film on the eye and helps to prevent evaporation. Tears are formed in several glands around the eye. The water layer is produced in the lacrimal

gland, located under the upper eyelid. Several smaller glands in the lids make the oil and mucus layers. With each blink, the eyelids spread the tears over the eye. Excess tears get drained in to the nasal meatus through the canaliculi and nasolacrimal duct. The connection between the tear ducts and the nasal passage is the reason that crying causes a runny nose. The term “Dysfunctional Tear Syndrome” is a better way to indicate the complex pathological condition which has been inappropriately referred to as “Dry Eye”[Figure 1].

Due to the irregular surface of the corneal epithelium, normal and undisturbed vision is dependent on the presence of an evenly distributed tear film and of a well moisturized ocular surface. Sufficient quantity of tears, regular composition and architecture of the tear film, normal lid closure, regular blinking and adequate tear fluid turnover are among the prerequisites to maintain this status. Whatever is the cause, failure in maintaining such equilibrium is the origin of the condition that we call “Dysfunctional Tear Syndrome”.

The stability of the precorneal tear film, the quantity and quality of the tears available for the ocular surface are changed in patients with Dysfunctional Tear Syndrome, so that the tear fluid cannot perform its function and becomes toxic for the ocular surface; symptoms appear, the corneal epithelium becomes compromised and metaplastic changes of the conjunctiva occur with mild interpalpebral hyperemia. If untreated, the Dysfunctional tear Syndrome can lead to a chronic inflammatory status with progression of the pathologic erosive changes of the cornea and the conjunctiva. About half of all people who wear contact lenses complain of dry eye.5,6 There are two potential connections between contact usage and dry eye. Traditionally, it was believed that soft contact lenses, which float on the tear film that covers the cornea, absorb the tears. However, it is also now known that contact lens usage damages corneal nerve

Vol. 22, No. 4, April - June, 2012258


sensitivity, which subsequently may lead to decreased lacrimal gland tear production and dry eye.7,8,9 The effect of contact lens on corneal nerve sensitivity is well established for hard as well as for soft and rigid gas permeable contact lenses.10,11,12 The connection between this loss in nerve sensitivity and tear production is the subject of current research.

Aging is one of the most common causes of dry eyes.5 This is because tear production decreases with age. It may be caused by thermal or chemical burns, or by adenoviruses (in epidemic cases). A number of studies have found that diabetics are at increased risk for the disease.8,9 Dry eyes also occurs or gets worse after LASIK5 (Figure 2) and other refractive surgeries (Figure 3), in which the corneal nerves are cut during the creation of a corneal flap.6 The corneal nerves stimulate tear secretion. Dry eyes caused by these procedures usually resolves after several months, but it can be permanent.

Abnormalities of the lipid tear layer caused by blepharitis and Rosacea, and abnormalities of the mucin tear layer caused by vitamin A deficiency, Trachoma, Diphtheric keratoconjunctivitis, mucocutaneous disorders and certain topical medications are causes of KCS.1 An eye injury or other problem with the eyes or eyelids4 such as bulging eyes or a drooping eyelid can cause KCS. Disorders of the eyelid can impair the complex blinking motion required to spread tears.6 Persons with KCS have elevated levels of tear nerve growth factor (NGF).1 It is possible that this ocular surface NGF plays an important role in ocular surface inflammation associated with dry eyes.1

Data from the last few years have estimated the prevalence of Dysfunctional Tear Syndrome in 10 to 20% of the adult population.3,4,5 Clinical experience shows that women represent the majority of patients suffering from Dysfunctional Tear Syndrome. This seems particularly true for postmenopausal women. A study has shown that 20% of postmenopausal women complain of Dysfunctional Tear Syndrome symptoms.8 Other medical history items associated with dry eye included history of arthritis, fractures, osteoporosis, gout and thyroid disorder. People with a history of allergies do have a significantly higher

age- and sex-adjusted prevalence of dry eye compared with people without a history of allergies. Among medications and supplements, only antidepressants, aspirin, and multivitamins were significantly or nearly significantly associated with age- and sex-adjusted prevalence of dry eye. Other medications that are not related to dry eye included angiotensin-converting enzyme inhibitors, antiadrenergic agents, antihistamines, antianxiety agents, calcium channel blockers, diuretics, antiemetics, parasympathetic agents, methyldopa, reserpine, and hormone use in postmenopausal women.

Studies found a protective effect for the use of ACE inhibitors. Studies have suggested that ACE inhibitors have anti-inflammatory effects. We can only speculate as to whether this is the basis for the connection. Further study may be worth pursuing. The joint relationship of arthritis and aspirin use with dry eye found that arthritis and aspirin dose were each independently associated with dry eye. No interaction was apparent. Among subjects with a history of gout, those not being treated had a significantly higher age and sex adjusted prevalence of dry eye, whereas those being treated had a similar prevalence to those without gout. A history of heavy drinking in the past was associated with a higher prevalence of dry eye. However, the current amount of alcohol consumed was not. Current cigarette smoking, and possibly past smoking, is related to dry eye, as is pack-years smoked and current packs smoked daily.

Caffeine use is associated with a lower age and sex adjusted prevalence of dry eye. Again, the reported amount consumed is largely irrelevant. Subjects who were examined during the months when indoor heating systems were in use reported more dry eye than those examined during the warmer months. Finally, there was no association between dry eye and time spent outdoors during the winter or the summer. So, smokers, past or current users of multivitamins, persons with a history of gout or thyroid disorder, and persons with diabetes were more likely to have dry eye. Persons consuming caffeine and persons with a higher total to HDL cholesterol ratio are less likely to have dry eye.

Figure 1 Flourescein staining of a patient of Dry eye

Figure 3 Flourescein staining of a patient of Dry Eye after RK

Figure 2 Flourescein staining of a patient of Dry Eye after refractive surgery



The Genesis of Ocular Surface Changes in the Dysfunctional Tear Syndrome

The increased tear water evaporation rate has been reported to be at the basis of the build-up of a hyper osmotic tear film. It is associated with a decreased tear fluid production and a consequently defective spreading of the tear.7 The tear film increases its osmolarity when the lacrimal gland secretion cannot keep the pace with such excessive tear evaporation.8 This can be the consequence on an absolute reduction in tear flow (absolute tear hyposecretion, tear deficient dry eye) with the incapability of maintaining an adequate spreading and efficacy of the lipid layer. However, it can also be associated with a theoretically sufficient tear flow for normal ocular surface . Recent data suggest that the hyperosmotic shift is a cause of inflammation and a frequent pathway to the development of damage to the ocular surface.9-13

Diagnosis Of Dysfunctional tear syndrome

The report of the Dry Eye Workshop addressing the advances in the understanding of the disease made over the past 10 years, defines the dry eye (Dysfunctional Tear Syndrome) as ‘’a multifactor tear and ocular surface disease resulting a discomfort, visual ocular surface disease resulting in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface’’.6 There are different dry eye severity levels that merit consideration each level is classified in 4 gradings.1

Grading A) Discomfort, Severity and Frequency

Grade 1: Mild and episodic:occurs under environmental stress

Grade 2: Moderate episodic or chronic, stress or no stress

Grade 3: Severe frequent or constant without stress

Grade 4: Severe and/or disabling and constant

B) Visual Symptoms

Grade 1 : None or episodic mild fatigue

Grade 2: Annoying and/or activity-limiting episodic

Grade 3 : Annoying, chronic and constant, limiting activity

Grade 4 :Constant and/or possibly disabling

C) Conjunctival Injection

Grade 1 : None to mild

Grade 2: None to mild

Grade 3 : +/-

Grade 4 :+/++

D) Conjuctival Staining

Grade 1 : None to mild

Grade 2: Variable

Grade 3 :Moderate to marked

Grade 4 :Marked

E) Conunctival Staining (severity/location)


Grade 2: Variable

Grade 3: Marked central

Grade 4: Severe punctate erosions

F) Corneal/Tear Signs


Grade 2: Mild debris, meniscus

Grade 3: Filamentary keratitis, mucus clumping, tear debris

Grade 4: Filamentary keratitis, mucus clumping tear debris, ulceration

G) Lid/Meibomian Glads

Grade 1: Meibomian glad disease (MGD) variably present

Grade 2: MGD variably present

Grade 3: Frequent

Grade 4: Trichiasis, keratinization, symblepharon

H) Fluorescein Tear Break-up Time (TBUT) (sec)

Grade 1: Variable

Grade 2: <10

Grade 3: <5

Grade 4: Immediate

I) Schirmer Score (mm/5 min)

Grade 1: Variable

Grade 2: <10

Grade 3 : <5

Grade 4 : <2

Vol. 22, No. 4, April - June, 2012260


Treatment of Dysfunctional Tear SyndromeSome fundamental steps should be taken into

consideration in the treatment of Dysfunctional Tear Syndrome.14-46

• The Ocular Surface is a system responding to the tear problem with multiple vicious cycles. Most of (if not all) the active pathogenic conditions should be recognized and addressed to in order to interrupt the greatest possible number of vicious cycles.32-35

• The treatment should reach a reasonable frequency, but this should be balanced with the risk of toxicity.

• The frequent use of preservative containing preparations associated with a low tear turnover may build-up the concentration of preservatives on the ocular surface, at a very high risk of epithelial toxicity and adverse effects on the structures we desire to cure.36-41

• The presence of some systemic factors (collagen disease, hormonal disorders, use of medications, etc.) should be considered.28-31

• The chronicity of the condition should be explained to the patient, along with the fact that it will take some time before the therapy may exert its effect and the condition improve.43-47

A list of treatment options follows, that should be considered while treating a dry eye. Once the aimed objective has been reached (e.g. disappearance of corneal punctuate staining by using aggressive topic steroidal therapy and very viscous tear substitutes), therapy should be dynamically changed (steroids tapering, reducing the viscosity of tear substitutes tapering, reducing the viscosity of tear substitutes, etc.) in order to reduce their toxicity and enhance long term efficacy. Other systemic factors merit consideration as well.19,20

Ø Increase Tear Film Volume21-27

• Systemic pilocarpine – cevimeline to stimulate lacrimal gland production

• Thick, viscous, volumetric tear substitutes

• Temporary insertion of punctual plugs (beware of the risk of building up inflammatory agents concentration on the ocular surface !)

Ø Improve Lubrication24-27

• Non-Newtonian tear substitutes which may lower their viscosity during blinking (as normal tear mucus does) will provide a more comfortable blinking.

Ø Improvement of Mucus Conditions25-27

• Even if not regularly available in many countries, different products are used or are under evaluation (gefarnate, P2Y2, S-15-HETE, Rebamipide, Ecabet,

etc.) in order to improve goblet cell and epithelial glycoprotein (mucins) secretion as well as to break the sticky mucous filaments (n-acetyl cysteine) formed on the ocular surface in certain conditions (filamentous keratitis, mucous fishing syndrome). Possible toxicity of long term use should be always considered (such as for acetyl – cysteine).

Ø Improve Corneal Epithelium23-28

• Semi compressive temporary eye patching, blocking the lid movement will decrease the damage produced by the shearing forces applied by the lid movement towards the unprotected epithelium.

• Temporary contract lenses will provide an alternative shield to lid movement induced damage. High gas permeability (Silicone-Hydrogel) lenses are recommended allowing for a stable, low riding fitting, with low trauma to the epithelium. Special care against infection should be observed.

• Amniotic membrane will protect the epithelium and provide anti inflammatory and growth factors for the ocular surface cells.

Ø Reduce Evaporation1,2,23,27,48-50

• Protective goggles will stabilize the atmosphere next to the eye surface preventing loss of moisture from the tear film.

• Meibomian gland medhanical expression will provide fluid lipids for the oily layer of the tear film possibly making it more effective.

• Lipidic tears might reduce the evaporation;

• Lateral tarsorraphy will reduce the area of evaporation.

• Lifestyle adaptation should be suggested, avoiding exposure to environmental stresses.

Ø Correct the Hyperosmotic Shift2,5,6,21-24,27,48-50

• Hypotonic tear substitutes which dilute the electrolyte concentration on the ocular surface.

• Compatible solutes which distribute between the tears and the intracellular fluids to protect against potential cellular damage from hyperosmotic tears.

Ø Treat the Lids11-13,47-50

• Correct blepharitis which is very often present.

• Incomplete blinking or night lid lad should be corrected or compensated by means of night time use of ointments or high viscosity formulations during the day.

• Consider lazy blinkers and suggest being aware fo the proble while performing vision related activities.

• Loose and floppy eye lids should be considered and corrected if possible.



References

1. Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: Delphi approach to treatment recommendations. Cornea 2006; 25(8):900-7.

2. Dry Eye Workshop (DEWS) Committee 2007. Report of the Dry Eye Workshop (DEWS). Ocul Surf 2007; 5(2):65-204.

3. Lambiase A, Micera A, Sacchetti M, et al. Alterations of tear neuromediators in dry eye disease. Arch Ophthalmol 2011; 129(8):981-6.

4. Nien CJ, Massei S, Lin G, Nabavi C, Tao J, Brown DJ, et al. Effects of age and dysfunction on human meibomian glands. Arch Ophthalmol 2011; 129(4):462-9.

5. Gilbard JP, Farris RL, Santamaria J. Osmolarity of tear microvolumes in keratoconjunctivitis sicca. Arch Ophthalmol 1978; 96(4):677-81.

6. Lemp MA, Bron AJ, Baudouin C, Benítez D,Castillo JM, Geffen D et al. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol 2011;151(5):792-8.

7. Ohba E, Dogru M, Hosaka E, et al. Surgical punctal occlusion with a high heat-energy releasing cautery device for severe dry eye with recurrent punctal plug extrusion. Am J Ophthalmol 2011; 151(3):483-7.

8. Baiza DL, Medrano PJ, Hernandez QE, Lozano A J, Alaniz JF et al. A comparative clinical trial of the efficacy of two different aqueous solutions of cyclosporine for the treatment of moderate-to-severe dry eye syndrome. Br J Ophthalmol 2010; 94(10):1312-5.

9. Abelson MB. Dry eye, today and tomorrow. Review in Ophthalmology 2000; 11:132-4.

10. External disease and cornea. Section Seven. Basic & Clinical Science Course. American Academy of Ophthalmology 2007-2008; 111-3.

11. Barabino S, Rolando M, Camicione P et al. Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammatory component. Cornea 2003; 22(2):97-101.

12. Bron AJ, Tiffany JM, Gouveia SM, et al. Functional aspects of the tear film lipid layer. Exp Eye Res 2004; 78(3):347-60.

13. Geerling G, Maclennan S, Hartwig D. Autologous serum eye drops for ocular surface disorders. Br J Ophthalmol 2004; 88(11):1467-74.

14. Schein OD, Munoz B, Tielsch JM, Bandeen-Roche K, West S. Prevalence of dry eye among the elderly. Am J Ophthalmol 1997; 124:723-8.

15. McCarty CA, Bansal AK, Livingston PM, Stanislavsky YL, Taylor HR. The epidemiology of dry eye in Melbourne, Australia. Ophthalmology 1998; 105:1114-9.

16. Caffery BE, Richter D, Simpson T, Fonn D, Doughty M, Gordon K. CANDEES: Canadian Dry Eye Epidemiology Study. Adv Exp Med Biol 1998; 438:805-6.

17. Klein R, Klein BEK, Linton KLP, DeMets DL. The Beaver Dam Eye Study. Ophthalmology 1991; 98:1310-5.

18. Klein R, Klein BEK, Lee KE. The changes in visual acuity in a population: The Beaver Dam Eye Study. Ophthalmology 1996; 103:1169-78.

Ø Control Inflammation11-13,47-50

• Topical steroids are very useful improving local conditions. Low penetration drugs or those with inactive metabolite formulations seem to be the most appropriate ways to reduce possibly severe complications. Repeated short term use, bolus, and tapering low dosages have been suggested.

• Topical NSAIDs have shown some degree of activity in short term usage. Risk of local toxicity and corneal melting in eyes with abnormal activiation of MMPs does not make a long term use of these preparations advisable.

• Systematic and possibly local Omega 3-6 Poly Unsaturated Fatty Acids therapy has been associated with improvement of the inflammatory expression on the ocular surface as well as improvement of signs and symptoms.

Topical cyclosporine A improves signs and symptoms. There is a long latent period between the initiation and benefit.13

Ø Supplement Growth Factors11-13

• The use of autoserum eye drops has been associated with increased conjunctival goblet cell expression and improvement of ocular surface.

Tear supplements, substitutes and lubricants should be used along with anti inflammatory agents and preventive procedures against evaporation or epithelial damage as well as methods to control the hyperosmotic shift and its effects. Failure to use a simultaneous multiple treatment approach will provide just temporary palliative results and may possibly delay or prevent the possibility of substantially improvement .

Some key processes in care management, such as elimination of systemic medication, environment intervention, computer work site intervention, and humidification of ambient air, appeared to be largely overlooked by eye care providers. Many physicians appear to focus on medication therapy alone, perhaps having firmer convictions about the effectiveness of medication therapy or rather feeling that education about environmental or lifestyle modification therapy for dry eye (or its documentation) would be time-consuming.

Others have noted that prescribing eye drops is the easiest and most secure method of satisfying patients.

Vol. 22, No. 4, April - June, 2012262


19. Klein R, Davis MD, Magli YL, et al. The Wisconsin Age-Related Maculopathy Grading System. Ophthalmology 1991; 98:1128-34.

20. Klein BEK, Klein R, Linton KLP, et al. Assessment of cataracts from photographs in the Beaver Dam Eye Study. Ophthalmology 1990; 97:1428-33.

21. Schein OD, Tielsch JM, Munoz B, et al. Relation between signs and symptoms of dry eye in the elderly. Ophthalmology 1997; 104:1395-401.

22. Bandeen-Roche K, Munoz B, Tielsch JM, et al. Self-reported assessment of dry eye in a population-based setting. Invest Ophthalmol Vis Sci 1997; 38:2469-75.

23. Mathers WD, Lane JA, Zimmerman MB. Tear film changes associated with normal aging. Cornea 1996; 15:229-34.

24. Gilbard JP. Dry eye disorders. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. Philadelphia, Penn: WB Saunders 1994: 257-76.

25. Andrews JS. Human tear film lipids I: composition of the principal non-polar component. Exp Eye Res 1970; 10:223-7.

26. Craig JP, Tomlinson A. Importance of the lipid layer in human tear film stability and evaporation. Optom Vis Sci 1997; 74:8-13.

27. Gilbard JP, Rossi SR, Heyda KG, Dartt DA. Stimulation of tear secretion and treatment of dry-eye disease with 3-isobutyl-1-methylxanthine. Arch Ophthalmol 1991; 109:672-76.

28. Bergman MT, Newman BL, Johnson NC. The effect of a diuretic (hydrochlorothiazide) on tear production in humans. Am J Ophthalmol 1985; 99:473-5.

29. Norn M. The effects of drugs on tear flow. Trans Ophthalmol Soc U K. 1985; 104:410-4.

30. Sator MO, Joura EA, Golaszewski T, Gruber D, Frigo P, Metka M, Hommer A, Huber JC. Treatment of menopausal keratoconjunctivitis sicca with topical oestradiol. Br J Obstet Gynaecol 1998; 105:100-2.

31. Mathers WD, Stovall D, Lane JA, Zimmerman MB, Johnson S. Menopause and tear function. Cornea 1998; 17:353-8.

32. Bron AJ, Tiffany JM. The meibomian glands and tear film lipids. Adv Exp Med Biol 1998; 438:281-95.

33. Warren DW. Hormonal influences on the lacrimal gland. Int Ophthalmol Clin 1994;34:19-25.

34. Lemp MA. Epidemiology and classification of dry eye. Adv Exp Med Biol 1998; 438:791-803.

35. Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol. 2003; 136(2):318-26.

36. Schein OD, Munoz B, Tielsch JM, Bandeen-Roche K, West S. Prevalence of dry eye among the elderly. Am J Ophthalmol 1997; 124(6):723-8.

37. Moss SE, Klein R, Klein BEK. Incidence of Dry Eye in an Older Population. Arch Ophthalmol. 2004; 122(3):369-73.

38. Moss SE, Klein R, Klein BEK. Prevalence of and Risk Factors for Dry Eye Syndrome. Arch Ophthalmol 2000; 118(9):1264-1268.

39. Lin PY, Tsai SY, Cheng CY, Liu JH, Chou P, Hsu WM. Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology 2003; 110(6):1096-101.

40. Miljanovi B, Dana R, Sullivan DA, Schaumberg DA. Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol 2007; 143(3):409-15.

41. Schiffman RM, Walt JG, Jacobsen G, Doyle JJ, Lebovics G, et al. Utility assessment among patients with dry eye disease. Ophthalmology 2003; 110(7):1412-19.

42. Reddy P, Grad O, Rajagopalan K. The economic burden of dry eye: a conceptual framework and preliminary assessment. Cornea 2004; 23(8):751-61.

43. Lee PP, Hilborne L, McDonald L, et al. Documentation patterns before cataract surgery at ten academic centers. Ophthalmology 1996; 103(8):1179-83.

44. Dry Eye Syndrome Preferred Practice Patterns. San Francisco, CA: American Academy of Ophthalmology; 1998.

45. American Academy Ophthalmology. Dry Eye Syndrome Preferred Practice Patterns. San Francisco, CA: American Academy of Ophthalmology; 2003.

46. Smith J, Nichols KK, Baldwin EK. Current patterns in the use of diagnostic tests in dry eye evaluation. Cornea 2008; 27(6):656-2.

47. Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf 2007; 5(2):108-152.

48. Pflugfelder SC, Tseng SC, Sanabria O; et al. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorder known to cause ocular irritation. Cornea 1998; 17(1):38-56.

49. Dry Eye Syndrome Preferred Practice Patterns. San Francisco, CA: American Academy of Ophthalmology; 2008.

50. Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):163-78.



Original Article

Comparative evaluation of the antiinflammatory effect of topical 0.1% dexamethasone sodium and topical 1% prednisolone acetate eye drops after

small incision cataract surgery in Indian eyesSomen Misra MS, Sulbha Gaydhankar MS, Rajen Mehta MS

Abstract Purpose: To compare the anti-inflammatory efficacy of topical 0.1% dexamethasone sodium and 1%

prednisolone acetate after uneventful small incision cataract surgery (SICS)with in the bag posterior chamber intraocular lens( PCIOL) implantation in Indian eyes.

Methods: 60 consecutive patients who underwent uneventful SICS with in the bag PCIOL implantation were randomly assigned to either of two study groups. Patients in both groups were similar in base line parameters. The anti-inflammatory efficacy of the two study drugs were compared by closely examining the operated eyes for inflammatory response and visual acuity. All the patients were followed up post operatively on day 1, day 2, day 7 and day 42nd and the severity of post inflammatory response was graded.

Results: All results were correlated with final visual outcome, which showed that topical 1% prednisolone acetate is clinically and statistically more effective in early postoperative period than dexamethasone sodium to control the inflammation in uneventful SICS.

Conclusion: The study showed that topical 1% prednisolone acetate is more effective than topical 0.1% dexamethasone sodium in controlling postoperative inflammation and in early visual rehabilitation in uneventful cataract surgeries in Indian eyes. However, the same cannot be said to be true in cases of cataract surgery with per operative complications.

. Del J Ophthalmol 2012;22(4):263-266. Key Words: Prednisolone acetate, Dexamethasone sodium, small incision cataract surgery, posterior

chamber intraocular lens, postoperative inflammation.

Hardly any literature is available regarding the comparative evaluation of anti-inflammatory effects of these two drugs in Indian eyes. Visual prognosis of patients after cataract surgery depends on various preoperative, intraoperative and postoperative factors, out of which postsurgical inflammation is the most important factor to the ophthalmologists. This postsurgical inflammation is due to various intraocular manipulations as irrigation of anterior chamber, injection of viscoelastic agent, handling of iris, intraocular lens implantation, etc. as described by Roper Hall MJ et al.1 All above intraocular manipulation leads to breakdown of blood aqueous barrier, leading to release of various chemical mediators of inflammation as prostaglandins, prostacyclins, leukotrienes, cytokines etc. and exudation of proteins in anterior chamber. However,

postoperative inflammation is usually self- limiting and immune mechanism plays a minor role in the inflammatory process. The exact mechanism of action of corticosteroids is still not known. They have many effects on the inflammatory and immune responses. The most important action of steroids is to inhibit the phospholipase A2 enzyme which is the rate limiting step for synthesis of prostaglandins and other chemical mediators of inflammation.2-3

Newer concept about steroids is that, they act as immunosuppressive agent. In the present study, we compared the efficacy of topical 0.1% dexamethasone sodium and 1% prednisolone acetate in controlling

Deptt. of Ophthalmology Rural Medical College, LoniMaharashtra

Correspondence to : Dr. Somen MisraE-Mail : [email protected]

Day 1 Day 2 Day 7 Day 4

Dexamethasone 29(97%) 29(97%) 13(43%) 5(17%)

Prednisolone 28(93%) 28(93%) 12(40%) 4(13%)

Postoperative daysCategory

TABLE 1. Incidence of Postoperative Pain

Vol. 22, No. 4, April - June, 2012264


postoperative inflammation following uneventful small incision cataract surgery (SICS) with in the bag implantation of posterior chamber intraocular lens (PCIOL). The study was conducted in a tertiary level hospital on 60 patients who underwent uncomplicated SICS, with in the bag PCIOL implantation during the last two years.

Methods

The study was carried out prospectively over a period of 1 years from February 2010 to January 2011. Sixty patients with senile cataract who underwent uncomplicated SICS with in the bag PCIOL implantation were enrolled in the study after obtaining informed consent. Approval for the study was obtained from the hospital ethical committee. The inclusion criteria were as follows: uncomplicated senile cataract, no previous ocular surgery, no previous ocular disease, not allergic to any drugs, uncomplicated SICS with PCIOL in the bag implantation. The exclusion criteria were as follows: bleeding disorders or on anticoagulant therapy, systemic disease such as hypertension, diabetes mellitus, ischemic heart disease, bronchial asthma, connective tissue disorders, immunological disorders and poor compliance.Preoperatively, all patients underwent visual acuity testing, measurement of intraocular pressure (IOP) and detailed slit lamp examination. All patients were operated by a single surgeon using similar instruments and techniques. Patients were randomly assigned to the two study groups,

Group A, who received 0.1% dexamethasone sodium and Group B who received topical 1% Prednisolone acetate (30 patients in each group). The postoperative medication was administered 6 times a day for 1 week and later tapered to 3 times a day for rest of period. Both received topical mydriatic and cycloplegic agent as homatropine 2% once a day. Postoperatively patients were followed up for 6 weeks as Day 1st, Day 2nd, Day 7th and Day 42nd. Grading of postoperative inflammation was done based on the following observations: circumcorneal congestion, corneal oedema, anterior chamber cells and flare. Analgesia was subjectively estimated based on patient’s complain of pain or discomfort.

ResultsAlmost all patients in both groups had pain, lid oedema

and ciliary congestion on the first 2 postoperative days. On the 7th postoperative day, 13 (43%) patients of Group A and 12 (40%) patients of Group B had mild to moderate pain (p >0.05). On day 42nd, there was no clinical significance in postoperative pain in both the groups [Table 1]. Also, all patients in Group A had ciliary congestion on Day 1 and 2, which was reduced to 10 (30%) on 7th postoperative day, whereas in Group B all patients had initial ciliary congestion which was reduced to 4 (13%) on 7th postoperative day (p < 0.01). No patient had congestion on 42nd day. 24 (80%) patients in Group A and 17 (57%) patients in Group B had

Postoperative daysGrade of aqueous flare


Slight flare 11(37%) 11(37%) 4(13%) 0

Moderate flare 2(6%) 2(6%) 1(3%) 0

Severe flare 0 0 0 0

Total 13(43%) 13(43%) 5(16%) 0

Postoperative daysGrade of aqueous flare


Slight flare 9(30%) 9(30%) 2(7%) 0

Moderate flare 1(3%) 1(2%) 0 0

Severe flare 0 0 0 0

Total 10(33%) 10(33%) 2(7%) 0

TABLE 2. Postoperative anterior chamber reaction

A. Dexamethasone group

B. Prednisolone group



corneal oedema on the 2nd postoperative day, and this number reduced to 10 (33%) and 5 (17%) respectively for the two groups on the 7th postoperative day (p <0.01). Corneal oedema was less in prednisolone group. Slit lamp examination showed that 5 (16%) patients in Group A and 2 (7%) in Group B showed mild to moderate iritis, quantified by cells and flare in the anterior chamber on the 7th postoperative day (p <0.01) [Table 2]. None of the patients had corneal oedema or iritis on the 42nd postoperative day. At the end of study period, in Group A, the best corrected visual acuity of 13 (43%) patients was between 6/60–6/18, 17 (57%) had more than 6/18. In Group B, 9 (30%) patients had the best corrected visual acuity between 6/60 – 6/18 and 21 (70%) had more than 6/18 (p < 0.01) [Table 3]. All these observations and results show that topical 1% prednisolone acetate is clinically and statistically more effective in early postoperative period than 0.1% dexamethasone sodium to control the inflammation in uneventful cataract surgeries.

Discussion Topical steroids are the most common methods of

administering steroids to the eye and following a single topical drop, steroid is measurable in human aqueous humour within 15-30 minutes.4,5,6 They are the main drugs that have been used so far for controlling postoperative inflammation after intraocular surgery. Steroids act by inhibiting production of factors (prostaglandins, leukotrienes etc.), which are critical in generating the

inflammatory response by multiple type of cells. When applied topically the drug has to penetrate the cornea across the three barriers: corneal epithelium–lipophilic in nature, corneal stroma–hydrophilic in nature and corneal endothelium–lipophilic in nature. Leopold IH et al7,8 showed that lipophilic layers of cornea provides resistance to polar (water soluble) molecules, whereas stroma being hydrophilic has resistance for lipid soluble molecules hence the substance used should be of biphasic polarity. Studies of Leibowitz and Kupferman et al,9 with radiolabelled dexamethasone and prednisolone have shown that acetate in the form of suspension can penetrate through a normal, uninflammed cornea with an intact epithelium most easily and can attain the maximum concentration of 2336 μg min /gm within 30 minutes of topical application in anterior chamber.10 Schoenwald et al11 also showed in experimental animals that prednisolone acetate suspension reaches the higher corticosteroid levels in anterior chamber amongst the other drugs used. The bioavailability and effectiveness of the anti-inflammatory drugs were studied by Leibowitz et Al10 by using radiolabeled polymorphonuclear leucocytes systemically before they invade the cornea. Commercially available preparation used for the present study of prednisolone was 1% prednisolone acetate in the form of suspension and of dexamethasone was 0.1% dexamethasone sodium solution. Later on, studies done by Leibowitz HM and Kupferman A10 showed that 1% prednisolone acetate was found more effective agent in suppressing anterior segment inflammation by using radiolabeled

TABLE 3. Postoperative visual acuity

A. Dexamethasone group

B. Prednisolone group

Grade of visual acuity

Day 1 Day 2 Day 7 Day 42 Best corrected visual acuity

>6/18 4(13%) 6(20%) 12(40%) 17(57%)

6/60-6/18 16(64%) 17(57%) 15(50%) 13(43%)

Total 20(67%) 23(77%) 27(90%) 30

<6/60 10(33%) 7(23%) 3(10%) 0

Total 30 30 30 30

Grade of visual acuity

Day 1 Day 2 Day 7 Day 42 Best corrected visual acuity

>6/18 5(17%) 8(26%) 16(64%) 21(70%)

6/60-6/18 17(57%) 17(57%) 12(43%) 9(30%)

Total 22(74%) 25(83%) 28(93%) 30

<6/60 8(26%) 5(17%) 2(7%) 0

Total 30 30 30 30

Vol. 22, No. 4, April - June, 2012266


polymorphonuclear leucocytes. Dexamethasone is the most potent of the corticosteroids, being 25 times more potent than the standard agent cortisol. It acts by inhibiting the action of phospholipase A2, and thereby preventing the release of arachidonic acid, which in turn is responsible for formation of prostaglandins and leukotrienes. Prednisolone acetate is the synthetic form with its prodrug as prednisone. It is 4 times more potent than cortisol and also has mineralocorticoid activity. The half –life is 12 hours and is less toxic as compared to dexamethasone sodium with half -life of 36-72 hours.The experimental data put forth by Leibowitz HM and Kupferman10,12,13 , with the studies in vivo showed that prednisolone acetate being biphasic in nature , attained maximum concentration of 2336 micrograms-minutes/gram in anterior chamber with epithelium intact, in un-inflammed eyes which showed that prednisolone acetate is more potent as compared to its sodium phosphate derivative, which showed concentration of 968 μg min/gm in same condition as it is available in solution form. Under similar conditions dexamethasone sodium 0.1% showed almost no penetration through the cornea with intact epithelium. At the same time their studies also showed that 1% prednisolone acetate and 0.1% dexamethasone sodium, had similar concentration in eyes with either corneal epithelium removed or inflamed eyes. This again showed biphasic nature of 1% prednisolone acetate is more potent than 0.1% dexamethasone sodium solution. Similar results were obtained by, Olejnik O et al14 and McGhee CN et al.15

Conclusion

The study showed that topical 1% prednisolone acetate is more effective than topical 0.1% dexamethasone sodium in controlling postoperative inflammation and in early visual rehabilitation in uneventful cataract surgeries in Indian eyes. Considering various adverse effects of steroids, as rise in intraocular pressure, secondary infections of topical steroids, new drug prednisolone acetate 1% is more effective in early visual rehabilitation than 0.1% dexamethasone sodium. This study recommends the use of topical 1% prednisolone acetate to control inflammation after uneventful cataract surgery in Indian eyes. The effect of 1% prednisolone acetate was not studied on cataract surgery with per operative complications, hence its effect in treating such cases is not known.

References

1. Roper Hall MJ: Stallard’s eye surgery. 7th edition: replica press pvt. Ltd. Delhi. Butterworth international edition 1989; Pg. 286 - 329.

2. Albert DM, Jackobiec FA : M basic Sciences. Principles and practice of Ophthalmology. 3rd edition. London: WB Saunders;2008.

3. Hardman JG Limbird et al (Eds). Goodman and Gillmans, “The pharmacological basis of therapeutics.” 10th edition. New York: Mcgraw Hill; Pg. 1649-1677.

4. Watson D, Noble MJ, Dutton GN, Midgley JM, Healey TM. Penetration of topically applied dexamethasone alcohol into human aqueous humor. Arch Ophthalmol 1988; 106:686-7.

5. McGhee CNJ, Noble MJ, Watson DG, Dutton GN, Fern Al, Healey TM, et al. Penetration of topically applied prednisolone sodium phosphate into human aqueous humour. Eye 1989; 3:463-7.

6. Watson DG, McGhee CNJ, Midgley JM, Dutton GN, Noble MJ. Penetration of topically applied betamethasone sodium phosphate into human aqueous humour. Eye 1990; 4: 603-6.

7. Leopold IH, Kroman HS, Green H. Intraocular penetration of prednisone and prednisolone. Trans Am Acad Ophthalmol Otolaryngol 1955; 59:771-8.

8. Leopold IH, Sawyer JL, Green H. Intraocular penetration of locally applied steroids. Arch ophthalmol 1955; 54; 916-21.

9. Leibowitz HM, Lass JH, Kupferferman A: Quantitation of inflammation in the cornea. Arch ophthalmol 1974; 92: 427-30.

10. Leibowitz HM, Kupferman A. Anti-inflammatory effectiveness in the cornea of topically administered prednisolone. Invest Ophthalmol 1974; 13:757-63.

11. Schoenwald RD and Boltralik JJ. A bioavailability of comparison in rabbits of two steroids formulated as high viscosity gels and reference aqueous preparation. Invest ophthalmol vis sci 1979; 18:61-6.

12. Leibowitz HM, Kupferman A. Bioavailability and therapeutic effectiveness of topical administered corticosteroids. Trans Am Acad ophthalmol otolaryngol 1975; 79:78-88.

13. Leibowitz HM, Berrospi AR, Kupferman A, Restropo GV, Galvis V, Alvarez JA. Penetration of topically administered prednisolone acetate into human aqueous humor. Am J ophthalmol 1977;83: 402-6.

14. Olejnik O, Weishecker CA. Ocular bioavailability of topical prednisolone preparations. Clin Jr Ophthalmol 1990;12(1): 2-11.

15. McGhee CN, Watsori DG, Midgley JM, Noble MJ, Dutton GN, Fern AI. Penetration of synthetic corticosteroids into human aqueous humor. Eye 1990; 4:526-30.



Original Article

Combined Surgery, Cryotherapy and Topical 0.002% Mitomycin C for Primary and Recurrent Corneal-Conjunctival Intraepithelial Neoplasia:

A Long -Term Follow Up

Abstract Purpose:- The aim of this study is to demonstrate the long term results of combined surgery, cryotherapy

and topical 0.002% mitomycin-C (MMC) for the management of primary and recurrent corneal-conjunctival intraepithelial neoplasia (CCIN).

Methods:- Five eyes of five patients with CCIN had surgical excision with cryotherapy. All cases received topical MMC (0.002%) 4 times a day for 12 weeks after surgery. The patients were followed up to two years.

Results: - All patients showed total cure with no recurrence during 2 years follow up period. Ocular irritation and mild conjunctival hyperemia were observed in 3 eyes during treatment with MMC. There were no serious complications noted at the end of the follow-up period.

Conclusion: - Combined surgery, cryotherapy and topical 0.002% MMC for the management of primary and recurrent CCIN was found to prevent tumour recurrence, especially in extensive and recurrent lesions, when surgical excision alone can not ensure a tumour free margin.

Del J Ophthalmol 2012;22(4):269-271. Key Words : corneal-conjunctival intraepithelial neoplasia, CCIN, topical mitomycin C, MMC, cryotherapy.

Saroj Gupta1 MS, R K Gupta2 DOMS

1. Peoples College of Medical Sciences and Research Centre, Bhopal (MP)2. Consultant Siddharth eye Hospital, Bhopal (MP) Correspondence to : Dr. Saroj Gupta E-mail : [email protected]

Corneal-conjunctival intraepithelial neoplasia (CCIN) is an uncommon benign slowly progressive lesion with low malignant potential.1 It generally occurs in the interpalpebral fissure, usually at the limbus, although it may be found elsewhere. According to limbal transition theory of Lee and Hirst, any alteration in the limbal stem cells may lead to abnormal epithelial maturation and metaplasia. CCIN may be associated with U-V light exposure, human papilloma virus infection and AIDS.2-4

The conventional therapy for CCIN is wide surgical excision and cryotherapy. However, high recurrent rates of up to 50%4,5 have been noted with multiple consequences such as destruction of normal limbal stem cells and conjunctiva causing corneal neovascularization and symblepharon formation. Adjunctive therapy such as beta radiation6 immunotherapy7,8 and topical chemotherapy9,10 has been used in an attempt to decrease the recurrences and to prevent or minimize scarring from repeated surgeries.

Topical MMC has been used for the treatment of CCIN since 1994 by several investigators.10-16 They reported favourable results from using various concentrations and durations of MMC for the treatment of primary and recurrent CCIN. However, corneal complications from MMC treatment are main concerns leading to dose and duration adjustment in later studies.11-13 It would be interesting to know whether the lower concentration of topical MMC 0.002% after surgical excision and cryotherapy would still be effective in the

Figure 1 Primary CCIN presenting as a papilliform mass at limbus with mature cataract.

Vol. 22, No. 4, April - June, 2012270


treatment of primary and recurrent extensive CCIN.Material and Methods

Five eyes of five patients (4 males and 1 female) with CCIN were recruited in this study. One patient presented with mature cataract and a papilliform mass at the nasal limbus (Figure-1). Two patients presented with recurrence after primary excision of the neoplasia (Figure-2a,b). The patients were in age group of 16 to 65 years with mean age of 49.2 years. A detailed slit lamp examination of all eyes was done. Patients’ demographic, pathologic and clinical data before treatment were recorded, these data included age, sex, tumour location, extent and size, symptoms, visual acuity and previous treatment. (Table-1).

Excision biopsy of the lesion was done using a non touch technique along with double freeze-thaw. Cryotherapy of the free conjunctival margins and the base of the lesion was done. Excised tissue was subjected to histopathological study. MMC 0.002% solution was prepared by adding 10 ml of sterile distilled water to 2 mg MMC. One milliliter of this solution was dilute with 9ml of distilled water.

The solution was refrigerated and protected from light. All patients received topical MMC (0.002%) 4 times a day for 12 weeks after surgery. The patients were followed up using slit lamp biomicroscopy for recurrences or any other

ocular manifestation at 1 week, 2 weeks, and every month for 6 months than every 3 months for another 18 months.

Results

Demographic data of the patients, clinical features, vision before and after treatment are listed in Table-1. Tumor occurred predominantly in males (4 males and 1 female). CCIN was on nasal side in 4 patients and on temporal side in 1 patient. Histopathological study of all excised neoplasia showed positivity for CCIN (Figure-3).Ocular irritation and mild conjunctival hyperemia was observed in 3 eyes during treatment period. They were relieved by topical preservative free artificial tears. There were no serious complications that necessitated stopping the treatment. One patient had cataract operation done in same eye 6 months after cessation of topical MMC treatment (Figure-4). No recurrence was seen in any of the patient during follow up of 2 years. Total cure was achieved in all eyes after surgery and MMC (0.002%) therapy (Table-1). Successful treatment was defined as the patient being clinically free from the tumor as observed using slit-lamp biomicroscopy and photography at last follow up (Figure-4). There were no long term complications detected at the end of the follow up period.

Figure 2 (a & b): Recurrent corneal-conjunctival intraepithelial neoplasia; Figure 3: Histopathological section of CCIN show-ing dysplastic nuclei; Figure 4: One year post treatment ,with intra ocular lens implantation done.

432 (b)2 (a)

S.no. Age/Sex Location Size of lesion in clock hrs.

Symptoms Previous Treatment

Results

1. 45/F Temporal limbus 3 FB Sensation Ex + Cryo 6/12 6/9 S

2. 62/M Nasal limbus 4 FB Sensation +DOV Nil PL+ 6/12 S

3. 16/M Nasal limbus 2 FB Sensation Ex+ Cryo 6/9 6/9 S

4. 65/M Nasal limbus 3 FB Sensation + DOV Nil 6/18 6/9 S

5. 58/M Nasal limbus 2 FB Sensation Nil 6/12 6/12 S

Visual acuityBefore Rx After Rx

FB – Foreign Body, DOV – Diminution of Vision

Ex – Excision. PL+ - Perception of sight. S- Successful. Rx – Treatment

TABLE 1. Demographic Data, clinical features and Results of Treatment



Discussion

CCIN is an ocular surface neoplasia commonly found among populations exposed to strong UV light.17 The tumor is usually found at the limbus, where the highest proliferative activity of the cells occurs.4 Although surgical excision is the mainstay treatment, one third of the patients require more then one surgical excision due to incomplete excision or recurrences. The reported recurrence rate after surgical excision varies from 20% to 40%.5,18 It requires a non-touch specialized technique of excision. Adjunctive cryotherapy combined with tumor excision reduced the recurrence rate to 9%.13,16

Several chemotherapeutic agents such as topical MMC9-13,15,16 5 –Fluorouracil10,19 and interferon7,8 have been tried in an attempt to minimize the tumor recurrence and the complications of extensive surgery. MMC is a potent cytotoxic agent that inhibits DNA synthesis. It functions in all phases of cell cycle, especially in rapidly dividing cells.9

Various concentrations and duration of treatment of MMC have been tried. Frucht-Pery et al10,13 reported the efficacy of 0.02% and 0.04% MMC 4 times daily for 4 consecutive weeks in the treatment of CCIN. Many investigators recommended prescribing topical MMC as a cycle therapy to avoid the side effects of the medication, such as 1 or 2 weeks of treatment followed by a few weeks of quiescence.9,10,13 Furthermore, some investigators used preoperative topical MMC and intraoperative local MMC as an adjunctive to surgical excision to prevent tumor recurrence.20 This study demonstrates that postoperative topical MMC 0.002% as an adjunctive to surgery and cryotherapy is effective in primary and recurrent CCIN. None of the patients showed recurrence up to two years of follow up. Complications of topical MMC as noted in our study were irritation, mild tearing and conjunctival hyperemia. All signs and symptoms were relieved by topical preservative free artificial tears. No serious or long -term complications were noted up to two years follow up.

To conclude, during a 2 years follow-up period the use of topical MMC as an adjunctive to surgical excision and cryotherapy was found to prevent tumour recurrence and provide excellent ocular surface healing.

References

1. Warmer MA, Jacobiec FA. Conjunctival diseases. Tumor, in: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. Vol. II, St Louis, MO: ANNE Patterson; 1997; 701-4.

2. Kiire CA, Dhillon B. The aetiology and associations of conjunctival intraepithelial neoplasia. Br J Ophthalmol 2006; 90(1):109-13.

3. Waddell KM, Lewallen S, Lucas SB, Atenyi-Agaba C, Herington CS. Carcinoma of the conjunctiva and HIV infection in Uganda and Malawi. Br J ophthalmol 1996; 80(6):503-8.

4. Lauer SA, JS, Meier JR, Human Papillomavirus type 18 in conjunctival intraepithelial neoplasia. Am J Ophthalmol 1990; 110:(1)23-7.

5. Erie JC, Campbell RJ, Liesegang TJ. Conjunctival and corneal intra-epithelial and invasive neoplasia. Ophthalmology 1978; 93(2):176-83.

6. Jones DB, Wilhelmus KR, Font RL. Beta radiation of recurrent corneal intraepithelial neoplasia. Trans Am ophthalmol Soc 1991; 89:285-301.

7. Boehm V, Hung A. Treatment of recurrent corneal and conjunctival intraepithelial neoplasia with topical interferon alpha2b. Ophthalmology 2004; 111(9):1755-61.

8. Eeqenazi S, Fry CL, Holly E. Treatment of biopsy proved conjunctival intraepithelial neoplasia with topical interferon alpha2b. Br J Ophthalmology 2005; 89(9):1221.

9. Gupta A, Muecke J. Treatment of ocular surface squamous neoplasia with Mitomycin C. Br J ophthalmol 2010; 94(5):555-8.

10. Fruct-Pery J, Rozenmen Y. Mitomycin C therapy for corneal intraepithelial neoplasia. Am J Ophthalmol 1994; 117:164-8.

11. Ballalai PL, Erwenne CM, Martins MC, Lowen MS, Barros JN. Long-term results of topical mitomycin C 0.02% for primary and recurrent conjunctival- corneal intraepithelial neoplasia. Ophthal Plast Reconstr Surg 2009; 25(4):296-9.

12. Rozenmen Y, Frucht-Pery J. Treatment of conjunctival intraepithelial neoplasia with topical drops of mitomycin C. Cornea 2000; 19:1-6.

13. Frucht-pery J, Sugar J, Baum J, Sutphin JE, Pe’er J, Savir H. Mitomycin C treatment for conjunctival- corneal intraepithelial neoplasia: A multicenter experience. Ophthalmology 1997; 104:2085-93.

14. Haas K, Ben Dor D, Levartovsky S. Treatment of conjunctival corneal intraepithelial neoplasia with topical mitomycin C. Arch Ophthalmol 1999; 117(4):544-5.

15. Daniell M, Maini R, Tole D. Use of mitomycin C in the treatment of corneal conjunctival intraepithelial neoplasia. Clin Exp Ophthalmol 2002; 30(2):94-8.

16. Prabhasawat P, Tarinvorakup P, Tesavibul N, Uipraserkul M, Kosirukvongs P,Boranapong W. Topical 0.002% mitomycin C for the treatment of conjunctival –corneal intraepithelial neoplasia and squamous cell carcinoma. Cornea 2005; 24:443-8.

17. Giaconi JA, Karp CL. Current treatment options for conjunctival and corneal intraepithelial neoplasia. Ocul surface 2003; 1(2):66-73.

18. Fraunfelder FT, Wingfield D. Management of intraepithelial conjunctival tumors and squamous cell carcinomas. Am J Ophthalmol 1983; 95(3):359-63.

19. Al Barrag A, Al shaer M, Al Matary N, Al Hamdani M. 5-Fluorouracil for the treatment of intraepithelial neoplasia and squamous cell carcinoma of the conjunctiva and cornea. Clin Ophthalmol 2010; (30)4:801-8.

20. Kemp EG, Hamett AN, Chatterjee S. Preoperative topical and intraoperative local mitomycin C adjunctive therapy in the management of ocular surface neoplasia. Br J Ophthalmology 2002; 86:31-4.



Techniques

Minimal Duration Cataract Surgery (MDCS) - Small Incision Cataract Surgery (SICS) without superior rectus stitch, no conjunctival flap and

no cauterization

Abstract The basis of manual small incision cataract surgery is the self sealing tunnel, which is able to deliver the

nucleus comfortably. The manual small incision cataract surgery is possible without application of superior rectus suture (truly stitch less) and construction of conjunctival flap. Elimination of these two steps will not only reduce the duration of surgery (MDCS - minimal duration cataract surgery) but have other advantages like better and early healing and lesser scarring. These modifications to the conventional technique will further refine the SICS and altering the position of incision to astigmatic neutral position makes this technique at par with phaco surgery. Minimal post-operative congestion, minimal scarring and astigmatism are the final outcome of surgery. The aim of this article is to present a description and analysis of the techniques and parameters involved in wound construction in MDCS

Del J Ophthalmol 2012;22(4):275-278. Key Words : Minimal duration cataract surgery, small incision cataract surgery, SICS.

Ram Lal Sharma MS, Praveen Panwar MS

Department of Ophthalmology, IGMC Shimla, (H.P). India

Correspondence to : Dr.RL Sharma E-mail : [email protected]

Cataract surgery techniques are continuously evolving over times; more so in last 2-3 decades. While intracapsular cataract extraction (ICCE) was the most commonly performed technique in the world till seventies; in later decades extracapsular cataract extraction (ECCE) with intraocular lens (IOL) became the most common procedure. These procedures have also been replaced by small incision cataract surgery (SICS) in last decade although phacoemulsification remains a popular technique with the limitation of cost and training. The complications are devastating with phaco surgery particularly during learning, and some of the surgeon can’t perfect this technique leading to loss of precious eyes. In comparison the SICS is simple to learn, easy to master, flexible to modify and have high safety margin.

Manual small incision cataract surgery (MSCIS) was developed mainly as a cost-effective alternative to phacoemulsification cataract surgery and will be the standard procedure where phaco surgery is not possible. The Western world graduated from ECCE to phacoemulsification. In the developing countries where the cost is a major issue and number of surgeries performed by a surgeon is large, duration of surgery is not only important for handling more patients but there is lesser tissue handling, coaxial light exposure and

less disturbances to ocular physiology. MSICS was developed after the advent of phacoemulsification, and hence it is a relatively younger technique than the latter. It is a safe, simple, consistent, stable, and cost-effective way of cataract removal. Wound construction plays a major role in MSICS, which may be more important than its role in phacoemulsification, where the size and shape and type of the wound remain same in most of the cases. In MSICS, one has the flexibility of incision size, shape and can be modified depending upon the type of technique, hardness of the nucleus, amount of astigmatism, and the condition of the endothelium.

The technique of Small Incision Cataract Surgery which is performed worldwide, consist of a superior rectus suture application with formation of conjunctival flap followed by cauterisation of conjunctival and episcleral vessels along with other surgical steps. We advocate some modification of this procedure where superior rectus stitch is not applied and conjunctival flap is not made, so no cautery is used.

TechniquesModifications in the existing methodsWithout bridle suture

Superior rectus bridle suture is required for better exposure. If the exposure is good without it why to subject the patient for additional risk of ptosis, haemorrhage, haematoma, conjunctival tears, and even perforation. Since this is a blind step, beginners particularly always find it

Vol. 22, No. 4, April - June, 2012276


difficult and invariably create complications. So Minimal duration cataract surgery (MDCS) is truly a stitch less surgery as no needle or thread is used.

Without conjunctival flap

Conjunctival flap is made to expose the limbus and sclera and later to cover the incision site. While the incision width is in micron so there is no need to create a large flap cutting many vessels and requiring cauterisation. There is no need of flap construction as without stitches one does not need to cover the wound as was practice in ECCE. Rather retraction of conjunctival flap will not only cause irritation but will also delay healing and cause more scarring.

Without cauterisation

Cauterisation is performed to create blood free field for tunnel construction at the cost of vascular supply; which is so vital for healing. Not only this, cautery destroys nerve supply and coagulate tissue and causes thinning of sclera which leads to delayed healing, scarring, astigmatism and staphyloma. One can have blood free field just by some irrigation during tunnel formation, once tunnel is formed the leaking vessels either stop bleeding or blood does not interfere in further manipulation as it does not enter into the anterior chamber.

Minimal Instruments

There are minimal number of instruments required for MDCS as the number of steps are less. During a standard procedure only 5 instruments are required i.e. wire speculum, two forceps (Hoskin’s, Mc-pherson’s), sinsky’s hook, cannula 2-way and 23 G. The instruments like scissors, artery forceps, cautery, superior rectus forceps, needle, and threads are not required.

Procedure detailsPosition of surgeon and eye exposure

The position of surgeon remains standard which is on head side but can be towards right side for right eye. The eye is exposed with simple wire speculum or a guarded speculum particularly in cases of narrower palpebral fissure or lid spasm; where one needs to hold the eyelids. If 1-2 mm of sclera is visible above the 12 o’clock limbus the surgery can be performed comfortably.

Incision and tunnel

As superior rectus suture is not applied so globe is stabilized by holding it near the limbus at 2 o’clock position with Hoskin’s forceps or a rounded holder. The external configuration of the incision is usually straight but can be curved and it is oblique supero-temporally in right eye and supero-nasal in left eye taking 10:30 clock hour of limbus

as centre point (Figure 1). The anterior limit of the incision is 1 mm behind the limbus, and the length of the incision (which is the distance between the two ends, but not along the curvature) varies from 5 to 6 mm for cortical cataract, and can be extended safely from 7 to 7.5 mm for brown and hard grade IV cataract. Optimal tunnel depth is usually half of the thickness of the sclera or about 0.3 mm. Incision is applied directly through conjunctiva and episcleral tissue without flap and cautery. Incision is usually sharp and there is minimal disturbance to conjunctival and episcleral vessels. Bleeding is usually minimal and can be cleared by continuous irrigation of fluid by assistant and it rarely interferes with tunnel dissection. The pocket of tunnel is dissected with crescent knife through the scleral fibres and corneal stroma and it is extended anteriorly 1.5–2 mm in cornea (Figure 2). The limbal tissue resists dissection, so care must be taken not to apply extra force forward, as this might cause uncontrolled forward corneal dissection after overcoming the sudden resistance during the dissection of the limbus and thus result in a premature entry into the anterior chamber or out of the cornea. As the dissection approaches the lateral end of the tunnel, the knife is tilted sideways while dissection is continued, creating a funnel-shaped tunnel of about 45 degrees. Thus, the internal aspect of the tunnel would be about 25% larger than the external incision. The crescent blade should be cutting while being brought out of the tissue. The pocket tunnel dissection is carried forward 1 mm into the clear cornea in front of the vascular arcade.

After the construction of the tunnel, the microkeratome is introduced into the tunnel and moved forward, until the tip of the keratome reaches the end zone of the tunnel

Upper NasalUpper Temporal

R L

Tunnel position Site of incision

Size of tunnel 5.5 x 2.5 mmSuperior-oblique 9-12 clock position

Site of incision in two eyes

Astigmatically neutral site

Between 2 standard meridians



(Figure 3). Then, the keratome tip is tilted downwards to enable perforation into the anterior chamber. After entering the anterior chamber, the keratome is moved laterally and forward causing the internal incision to direct itself in a curved fashion parallel to the limbus. By moving posteriorly, the internal opening will move towards the limbus, and valve action will be lost leading to leakage.

Capsular opening

This can be capsulotomy or capsulorrhexis, but rhexis should be either larger in size or can be enlarged by giving small cuts (2-3) on the margin with capsulotomy needle (Figure 4). Tunnel is extended before hydroprocedures so that nucleus can be delivered easily (Figure 5).

Hydro-procedures

The techniques of hydro-dissection and delineation remains the same, but these two procedures can be combined with hydro-delivery of the nucleus (Figure 6).

Nucleus delivery

The nucleus can be delivered in any of the three ways. It can be done either by hydro or visco or vectis delivery (Figure 7). In small and soft nucleus and fully opened eye lids, the nucleus is hydro-delineated and lifted up simultaneously out of the capsular bag and engaged in the tunnel, which is opened with the back of hydro-

cannula, and fluid is pushed towards 6 o’ clock position and nucleus comes out easily. It can be done in a single step where hydro-dissection, delineation and delivery (D3) are done simultaneously and it causes least damage to the endothelium. The hydro-delivery is not possible in deep set eye, rigid pupil, pseudoexfoliation and inadequately opened eye. In such situation visco delivery or vectis delivery is done while holding the eye at 5-6 clock hour position with one hand and delivery done with other. Nucleus delivery is more difficult in left eye. After this posterior chamber (IOL) is implanted into bag (Figure 8).

Discussion The concept of cataract surgery was given by the

famous Indian physician Sushruta (6th century BC), who described it in his work the Sushruta Samhita.1 In the 1940s Harold Ridley introduced the concept of implantation of the intraocular lens.2 In 1967, Charles Kelman introduced phacoemulsification, a technique that uses ultrasonic waves to emulsify the nucleus of the crystalline lens. Self-sealing cataract incisions were mentioned by Kratz et al3 in 1980 and by Girard in 1984.4,5 Kratz thought of scleral tunnel as an astigmatic neutral way of entering the anterior chamber. In 1984, it was shown by Thrasher et al that a 9.0-mm posterior incision induces less astigmatism than a 6.0-mm limbal incision.6 In 1990, Michael McFarland developed a sutureless incision7 and Pallin8,9 described a Chevron shaped incision. During the same period Singer10 popularized the frown

Figure 1: Supero-oblique Conjunctivo-scleral Incision mark with blade; Figure 2: Supero-oblique tunnel construction with crescent knife; Figure 3: AC entry with keratome tunnel width 2.5mm; Figure 4: Capsulorrhexis; Figure 5: Tunnel extension before hydroprocedures so that nucleus can be delivered along; Figure 6: Hydroprocedures – hydrodissection, delineation and elevation of nucleus Figure 7: Viscodelivery of nucleus; Figure 8: IOL implantation.

4

7

3

65 8

21

Vol. 22, No. 4, April - June, 2012278


incision. The supero-temporal location of the incision is far from the two primary meridians (vertical or 90o and horizontal or 180o) of cornea. So any flattening of cornea due to scarring affects the corneal curvature equally so lesser chances of astigmatism in comparison to the incision along the primary meridian. When incision is located superiorly, both gravity and eyelid blinking tend to create a drag on the incision. These forces are better neutralized with temporal incision because it is parallel to the vector of the forces. Superior temporal incision is also free from the effect of gravity and eye lid pressure and tends to induce less astigmatism.11 With the use of this technique overall surgical time is reduced to 5-8 minutes by eliminating three surgical steps - superior rectus stitch, conjunctival flap and cautery. There are also no chances of postoperative ptosis as superior rectus suture is not applied. The healing of incision is also very fast as conjunctival vessels are patent and epithelialisation covers the clean incision site quickly. This technique is being done in our set up for last four to five years with good comfort and visual outcome. A supero-temporal tunnel of 5.5 mm is constructed in right eye and supero-nasally in left eye. The surgically induced astigmatism (SIA) is minimal (less than one diopter) whereas our superior scleral incision always gave this value above 1D. When the tunnel length exceeded beyond 5.5 mm the astigmatism was noted (unpublished data). There is hardly any contraindication to this procedure but for beginners some situations like deep set eyes and narrow palpebral fissure, non dilating pupil, pseudoexfoliation, hypotony, bleeding tendencies (hypertension, patients on anticoagulants) are relative contraindications. The surgery is performed under peribulbar block using the same size and type of incision (straight to slight frown). Nucleus delivery is done by hydro-expression, visco-expression, or by irrigating vectis depending upon the comfort of expression one can choose either of the three.

The site supero-temporal (right) or supero-nasal (left) incision was chosen because there is more space on sides than superiorly because superior rectus suture is not applied. Planes of incision and intraocular manipulations are more accurate as eye is straight rather than in down gaze as in superior rectus stitch. The superior rectus stitch

References

1. Sharma PV, Suśruta-Samhitā. Vol II. Varanasi, India: Chaukhambha Visvabharati Oriental Publishers & Distributors: 2001.

2. Apple DJ, Sims J. Harold Ridley and the invention of the introcular lens. Surv Ophthalmol 1996; 40(4):279-92.

3. Kratz RP, Colvard DM, Mazzocco TR. Clinical evaluation of the terry surgical keratometer. Am Intraocular Implant Soc J 1980; 6:249–51.

4. Girard LJ, Hofmann RF. Scleral tunnel to prevent induced astigmatism. In: Emery JM, Jacobson AC, editors. Current concepts in cataract surgery: Proceedings of the eight biennial cataract surgical congress Norwalk. Appleton-Century- Crofts;1984. pp. 101–2.

5. Girard LJ. Origin of the Scleral tunnel incision. J Cataract Refract Surg 1995; 21:7.

6. Thrasher BH, Boerner CF. Control of astigmatism by wound placement. J Am Intraocul Implant Soc 1984; 10: 176–9.

7. Mcfarland M. Surgeon Undertakes Phaco, Foldable IOL series sans sutures. Ocular Surgery News.1990:1.

8. Pallin SL. Chevron incision for cataract surgery. J Cataract Refract Surg 1990; 16: 779–81.

9. Pallin SL. Chevron sutureless closure: A preliminary report. J Cataract Refract Surg 1991; 17:706–9.

10. Singer JA. Frown incision for minimizing induced astigmatism after small incision cataract surgery with rigid optic intraocular lens implantation. J Cataract Refract Surg 1991; 17:677–88.

11. Gokhale NS, Sawhney S. Reduction in astigmatism in manual small incision cataract surgery through change of incision site. Indian J Ophthalmol 2005; 53:201–3.

application is a blind procedure and difficult for some particularly beginners; so it invariably leads to bleeding, subconjunctival haemorrhage, damage to muscle tendon and rarely perforation. Patient has less tissue trauma, less pain and no chance of surgical ptosis post operatively. So this technique is recommended for all those surgeons who are doing SICS routinely and this will further refine their technique.



Case Report

Canalicular DacryolithiasisShakeen Singh MS, Rubina Tuli Soni MS, Vyankatesh Aironi MD, Baljeet Singh Dhillon MS

Abstract Dacryolith is the name given to a stone in the lacrimal system i.e. canaliculus, lacrimal sac or nasolacrimal

duct. It occurs because of impaired lacrimal drainage leading to stasis of tears. It’s being underdiagnosed because of many reasons. We have come across four patients with chronic local infection which were proved to be canalicular dacryolithiasis. Non invasive imaging procedure like ultrasound also helped in confirmation of diagnosis.

Del J Ophthalmol 2012;22(4):281-283. Key Words : lacrimal drainage, imaging, dacryolithiasis

Deptt. of OphthalmologySri Guru Ram Das Institute of Medical Sciences, Amritsar Correspondence to : Dr. Shakeen SinghE-Mail : [email protected]

Dacryolith is name given to stone in lacrimal system i.e. canaliculus, lacrimal sac (L.sac) or nasolacrimal duct (NLD). It is a common condition but is often underdiagnosed.1 Most commonly these are seen in L.sac, rarely in canaliculus and hardly in NLD. Dacryolithiasis is a sequale of chronic infection of the L.sac in about 30% of patients.2 Some times these are seen as concretion, or as a by-product of mycotic infection, or collection around some nidus like eye lash but basic reason is stasis of tears.3,4 The symptoms of these patients often lead to a misdiagnosis of chronic dacryocystitis. A thorough history, examination and investigations can confirm the diagnosis of dacryolithiasis so that appropriate treatment can be done for the patient. We are presenting four cases of canalicular stone referred to our Out Patient Department (OPD) for dacryocystorhinostomy (DCR).

Case 1A 75 years old lady presented to us in year 2006, with

history of swelling over the medial end of her left upper lid,

with discharge since long (Figure 1). She was being treated for this but was not relived. In fact she was referred for sac surgery by the primary treating ophthalmologist thinking it to be chronic dacryocystitis. Examination revealed pouting upper punctum with discharge and swelling localized to upper canalicular area. Seeing the location and consistency of the canalicular swelling, detailed history was elicited, specifically about renal/biliary stones. After routine investigations, and medical fitness pt was taken up for surgical exploration under local anesthesia. While trying to milk out the canalicular contents small mass prolapsed out of punctum. Then canaliculus was opened by single snip procedure to explore and remove that mass. Canalicular Diverticulosis or some canalicular growth was in mind. After removing this piece, canalicular curettage was done

which exposed multiple stones of different sizes, shapes consistency and physical appearance (small, big, rough, smooth, lobulated like mulberry, opaque and translucent). Canaliculus was washed with saline and povidone iodine 5% solution thoroughly and eye was patched for 24 hours. She was started on systemic antibiotic and anti inflammatory drugs. Two separate specimens were sent for investigation; mass piece for histopathology while stones for chemical analysis. Pt was kept under regular follow-up.Histopathology ruled out mycotic infection and revealed

Figure 1: From left to right: case 1 showing localized swelling over Left upper canaliculus; case 2 showing localized swelling over right upper canaliculus and case 4 showing swelling over right lower canaliculus.

Vol. 22, No. 4, April - June, 2012282


chronic benign granulomatous lesion and the stone analysis revealed a calcium phosphate (Figure 2). Blood tests of the patient revealed normal biochemistry.

Case 2A 65 years old man with no systemic problem reported

to us in year march 2006 with a complaint of swelling right upper lid localized to medial canthal area (Figure 1). There was history of mild epiphora but no frank discharge. Punctal examination revealed pouting mass giving the impression of chronic canaliculitis. Patient was non diabetic, non hypertensive, normal biochemistry, with no history of any systemic stone formation.Under local anesthesia, and all aseptic precautions, the canaliculus was exposed after slit opening the punctum. The mass was taken for histopathology. In this patient we were able to milk out a grayish white mulberry shaped single stone of about 5 mm in size. The stone was sent for biochemical analysis. The histopathology of the tissue ruled out mycotic infection and revealed chronic granulomatous type of lesion while the stone analysis showed calcium phosphate. Patient was started on topical antibiotics and systemic antibiotic and

Figure 2: Per operative picture of case 4 showing mulberry shaped stone being expressed from left lower canaliculi (left) and report of stone analysis of case 1 (right).

anti inflammatory drugs.Case 3

A 50 years old male presented to us in 2010 with swelling over the right lower lid. Express evacuation was attempted and the available material was sent for examination specifically for mycotic infection and was reported negative. Surgical exploration revealed multiple small stones. Similar post operative management was done.

Case 4A 35 years old male with swelling of Right lower lid

(Figure 1) presented to us in 2011. Similar work-up was done for him and canalicular exploration revealed single mulberry shaped stone (Figure 2). Similar post operative management was done. These patients were closely followed up for 6 months (1st 3 patients) for any watering, discharge, collection or recurrence of swelling or growth. The 4th patient is still being followed. All cases showed good recovery with no epiphora or recurrence of the disease (Figure 3).

Figure 3: Postoperative picture of case 1,2 and 4 (left to right) showing normal skin and absent swelling.



DiscussionMost common presentation of patients with canalicular

stone is epiphora followed by swelling localized to that specific area; medial end of the lids, if canalicui are involved and medial canthal area, if L.sac is involved. Other presenting symptoms are discharge from the eyes or pouting punctum on the involved lid. Most of these patients have had at least one attack of acute infection of the NLD system. Rarely one can palpate this mass in the region of the Lacrimal system.5-6 Syringing often reveals regurgitation or resistance. Investigations for confirmation are Dacryocystography, B-scan or C T Scan.7 But most of these investigations are not available every where, so proper history and local examination is most helpful to reach the diagnosis.

Ultrasound offers an advantage over other invasive procedure and we believe that it can be used as an initial screening test in cases of suspected dacryolith.

References

1. Wilkins RB, Pressly JP. Diagnosis and incidence of lacrimal calculi. Ophthalmic Surg 1980; 11:787–9.

2. Wilhelm KE, Hofer U, Textor HJ, Boker T, Strunk HM, Schild HH. Dacryoliths: nonsurgical fluoroscopically guided treatment during dacryocystoplasty. Radiology 1999; 212:305–6.

3. Hawes MJ. The dacryolithiasis syndrome. Ophthal Plast Reconstr Surg. 1988; 4:87–90

4. Jay JL, Lee WR. Dacryolith formation around an eyelash retained in the lacrimal sac. Br J Ophthalmol 1976; 60:722–5.

5. Orbit, eyelids, and lacrimal system: 2003–2004 basic and clinical science course, Vol. 7. American Academy of Ophthalmology, USA, 2003, p 28o.

6. Som PMM, Curtin HD. Head and neck imaging (3rd ed). St. Louis, MO: Mosby Inc 1996, pp 1153–1155.

7. Dutton JJ. Standardized echography in diagnosis of lacrimal drainage dysfunction. Arch Ophthalmol 1989; 107(7):1010-2.

Online Submission of Manuscript has started

Delhi Journal of

First TimeOphthalmology

Website:http://submission.djo.org.in

Dr. Rajesh SinhaEditor DJO &

Associate Professor of OphthalmologyRoom No. 479, 4th Floor,

Dr. R.P. Centre for Ophthalmic Sciences,All India Institute of Medical Sciences,

Ansari Nagar, New Delhi - 110 029Ph.: 011-65705229 w Website: dosonline.org



Case Report

Ocular Myocysticercosis : An unusual cause of Ptosis with involvement of Levator Palpebrae

Superioris and Superior Rectus MuscleKirti jain MS, KPS Malik MS, VK Malik MS, Charu Jain MS

Abstract Cysticercosis is the most common parasitic disease of nervous system. Unusual location of the cyst may

result in uncommon manifestation. Ocular cysticercosis can involve both the intraocular and extra ocular muscle. We are reporting the unusual case of ocular cysticercosis involving levator palpebrae superioris and superior rectus muscle. A 6 year old boy presented with painless unilateral ptosis and restricted ocular movement superiorly. He was diagnosed to have ocular cysticercosis by computed tomography (CT) Scan of Skull & Orbit left eye. Enzyme – linked immunosorbent assay for serum antibodies against cysticercosis was also found to be positive. The patient was managed conservatively and dramatic improvement was seen on a therapeutic trial of albendazole and oral steroids.

Del J Ophthalmol 2011;22(4):285-286. Key Words : ocular cysticercosis, ptosis, albendazole.

Cysticercosis is common in endemic country like India but its diagnosis by ophthalmologist is very challenging because of its different clinical presentation. Cysticercosis is considered the most common parasitic disease of central nervous system.Cysticercus cellulosae, the larval form of tapeworm Taenia solium, occasionally infests humans because of drinking contaminated water, eating uncooked vegetables infested with the eggs of worm, or rarely by autoinfection. Cyst is endemic

in the developing countries of Latin America, Asia and Africa especially area with poor hygiene.1 About 40% of persons infested by the parasite have ocular cysticercosis.2, 3 The extra ocular muscles are the most common site involvement of orbital cysticercosis. However the lateral rectus, medial rectus and superior oblique muscles have been found to be affected to a greater extent.4 In our case the cyst was located in the levator palpebrae superioris (LPS) and superior rectus (SR) muscles of the left eye which is one of the less common sites.

Case reportA six year old boy presented in our out patient

department (OPD) with progressively increasing painless swelling and drooping of left eyelid for 2 month. Examination of the left upper eyelid revealed ptosis and

Deptt. of ophthalmology, Subharati Medical College,Meerut, U.P, India

Correspondence to : Dr. Kirti Jain E-Mail : [email protected]

Figure 1(a & b) : Photograph at presentation shows ptosis and swelling of the left eyelid and restricted movement on upward

1(a) 1(b)

Vol. 22, No. 4, April - June, 2012286


Figure 3 (a & b) ): Photograph of patient after 15 days of treatment shows normal upper lid and full movement on upward gaze.

2 3(b)3(a)

References

1. Pushker N, Bajaj MS, Chandra M, Neena. Ocular and orbital cysticercosis. Acta Ophthalmol Scand 2001; 79:408-13.

2. Mukherjee PK, Agrawal S. Subconjuntival twin cysticercosis.Indian J Ophthalmol. 1975; 23:28-9.

3. Kaliaprumal S, Rao VA, Parija SC. Cysticercosis of eye in South India-a case series. Indian J Med Microbiol 2005; 23:227-30

4. Sundaram PM, Jayakumar N, Noronha V. Extraocular muscle cysticercosis - a clinical challenge to the ophthalmologists. Orbit 2004; 23:255-62.

5. Duke-Elder’s System of Ophthalmology. St. Louis: CV Mosby 1978. Cysticercosis; p. 40.

6. Sekhar GC, Lemke BN. Orbital cysticercosis. Ophthalmology 1997; 104:1599-604.

7. Raina UK, Taneja S, Lamba PA, Bansal RL. Spontaneous extrusion of extraocular cysticercus cysts. Am J Ophthalmol 1996; 121:438-41.

restricted movement on upward gaze (Figure 1 a & b). All other extraocular movements were within normal limits. The sclera and cornea were normal, and the pupils were bilaterally symmetrical and reacting to light. Fundus was normal. Neurological examination was within normal limit except left ptosis. General physical and systemic examination was within normal limits. CT study of skull and orbital left eye showed a 6.9 X 6.9 X 15.7 mm size mildly irregular cystic area in left SR/LPS complex with mild enhancement of muscle and generalized oedema in the left eye lid (Figure 2). The remaining extraocular muscles, eyeball and optic nerve of the left eye were normal. The right eye was normal, and there was no intracranial focal lesion. Enzyme linked immunosorbent assay for serum antibodies against cysticercosis was positive. The complete blood count was normal, with eosinophilia. The child was diagnosed as a case of cysticercosis, and treated with oral prednisolone and albendazole. After 15 days of follow up there was marked improvement of ptosis (Figure 3 a &b).

DiscussionThe first case of ocular cysticercosis was reported by

Semmering in 1830.5 Ocular or adnexal involvement occurs in 13 to 46% of infected patients. Ocular manifestation may be devastating as the cysticercus enlarges. In the Indian literature, the ocular adnexa is the most common site.6 Whereas posterior segment involvement is more common in western people. The most damaging location is intravitreal and sub-retinal location which lead to blindness in 3 to 5 years unless the parasite is removed. Cysticercosis is easily diagnosed by orbital imaging as its appearance is highly specific. CT and Magnetic Resonance Imaging not only confirm the diagnosis but also help to rule out neurocysticercosis. Tissue diagnosis is not essential for

starting treatment. Medical therapy with albendazole and oral steroid is recommended for the extra ocular muscle form and retro orbital cysticercosis, in these cases dramatic improvements have been reported.4,7 However therapy must be individualized according to the location of the parasite and tailored according to the activity of the disease. Intraocular cyst requires timely surgical removal to obviate sight threatening sequelae.1 In our patient cyst was present in the SR/LPS muscles complex and patient respond well to systemic albendazole and steroid therapy.

In conclusion, cysticercosis is a common clinical entity in India. It should be considered in patients who present with restricted ocular motility and inflammatory signs.

Figure 2 : C T study of skull & orbital left eye showed cystic area in left SR/LPS complex.



Case Report

Atypical Presentation of Primary Non-Hodgkin Lymphoma of the Lacrimal Gland

Abstract Primary Non-Hodgkins lymphoma (NHL) of the orbit is an uncommon clinical condition. We report an unusual

case of primary NHL of the lacrimal gland in a 30-year-old male with atypical clinical and radiological features. He presented with a progressive proptosis of the left eye with inferonasal displacement of the eye ball. Histopathological examination of the excised lacrimal mass revealed findings consistent with diffuse, low grade, non-Hodgkin lymphoma (B-cell). Postoperatively, orbital radiotherapy was advised. At two years follow-up, there was no local or systemic recurrence.

Del J Ophthalmol 2012;22(4):287-288. Key Words : primary non-hodgkins lymphoma, NHL, proptosis

Bhavna Chawla MS, Seema Kashyap MD, Sanjay Sharma MD, Mandeep S. Bajaj MD, Neelam Pushker MD, Mahesh Chandra MD, Supriyo Ghose MD

Primary Non-Hodgkin lymphoma (NHL) of the orbit is relatively uncommon, representing 8-10% of extranodal NHL and only 1% of all NHL.1 These lesions are located in the lid, retrobulbar space, lacrimal glands and conjunctiva, with an incidence of bilateral disease in 30% cases.1 We report an unusual case of primary NHL of the lacrimal gland with atypical clinical and radiological features.

Case DescriptionA 30-year-old male presented with complaints of a

mass above the left eye since 3 years, which was gradually increasing in size. On examination, proptosis of the left eyeball with inferonasal displacement of the globe was noted (Figure 1A). A well circumscribed, firm, non-tender mass was palpable in the superior orbit. Ocular motility was restricted in upgaze. Anterior segment and fundus evaluation was unremarkable. Visual acuity was 6/6. There were no inflammatory signs, nor any evidence of regional or systemic lymphadenopathy. Contrast-enhanced orbital CT (Figure. 1B) showed a well defined, mildly enhancing, soft tissue mass lesion in the region of the left lacrimal fossa, not separable from the lacrimal gland. It was causing mass effect on the globe and showed multiple foci of calcification. There was scalloping of the adjacent bony orbit but no destruction.

Based on the clinical and imaging features, a working diagnosis of benign mixed lacrimal gland tumor was made and the tumor was surgically excised in toto via an anterior orbitotomy. Gross examination showed a well

circumscribed, soft tissue mass measuring 4.0 x 3.5 x 1.5 cm, and the cut section was firm, grey-white in colour. Histopathological examination (Figure 1C) revealed diffuse sheets of rounded atypical lymphoid cells with moderate amount of cytoplasm, round to oval nuclei, and dispersed coarse chromatin with one or more nucleoli. Mitosis was frequent. Immunohistochemistry showed strong expression for LCA and CD20 (B-cell) in the tumor cells (Figure 1D), while pankeratin and S-100 were negative. Findings were consistent with diffuse, low grade, non-Hodgkin lymphoma (B-cell). Detailed systemic workup including complete blood counts, liver function tests, peripheral blood smear and thoraco-abdominal CT revealed no abnormality. Post-operatively, orbital radiotherapy was advised. At two years follow-up, there was no local or systemic recurrence.

DiscussionLesions of the lacrimal gland often present with

challenges in diagnosis and management. Lymphomatous lesions of the orbit include a broad spectrum ranging from reactive lymphoid hyperplasia to malignant lymphomas of various types. They occur most commonly in patients older than 60 years, with women more affected than men. Low-grade tumors are mainly localized to the orbit but high-grade tumors may extend to involve the bone, ethmoid sinuses and brain. Systemic involvement may be associated in 20-35% of cases.1 Among epithelial tumors, pleomorphic adenoma is the most common benign epithelial tumor affecting the lacrimal gland. These tumors generally have a slow progressive onset as a painless, superolateral orbital mass in a middle-aged person.2 Management is by complete surgical excision, without prior incisional biopsy. Imaging features are usually characteristic. The epithelial neoplasms arise focally within the lacrimal gland and grow in a centrifugal manner in all directions, sometimes indenting

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, AIIMSNew Delhi - 110029

Correspondence to : Dr.Bhavna Chawla E-mail : [email protected]

Vol. 22, No. 4, April - June, 2012288


Figure 1(a): (A) Clinical photograph at presentation. (B) Contrast-enhanced coronal CT scan of orbit showing soft tissue mass involving the left lacrimal gland with multiple calcific foci and scalloping of the adjacent bone. (C) Photomicrograph showing lymphoma cells infiltrating normal lacrimal gland tissue (H& E stain, x 100). (D) Immunohistochemistry showing diffuse positivity for CD20 (x 100).

References

1. Weber AL, Rahemtullah A, Ferry JA. Hodgkin and non-Hodgkin lymphoma of the head and neck: clinical, pathologic, and imaging evaluation. Neuroimag Clin N Am: 2003; 13:371– 92.

2. Shields CL, Shields JA. Lacrimal gland tumours. Int Ophthalmol Clin 1993:33:181-8.

3. Mafee MF, Edward DP, Koeller KK, Dorodi S. Lacrimal gland tumours and simulating lesions. Clinicopathologic and MR imaging features. Radiol Clin North Am 1999; 37: 219-39.

4. Hughes GK, Miszkiel KA. Imaging of the lacrimal gland. Seminars in Ultrasound, CT and MRI 2006; 27: 476-91.

5. Rootman J. Diseases of the orbit: a multidisciplinary approach, 2nd ed. Philadelphia, PA: Lippincott, Williams & Wilkins, 2003.

the globe, distorting the muscle cone and creating fossa formation in the orbital walls.3 In contrast, lymphoid lesions of the lacrimal gland mould themselves around existing orbital structures in ‘putty’ like fashion, without enlarging the orbit.4,5 While bony changes in the lacrimal fossa may be produced by lacrimal epithelial tumors, lymphoid lesions rarely produce bone changes.3

Our case had unusual clinical and radiological features for an orbital lymphoma. The patient was a young adult, the tumor was unilateral and was not associated with systemic involvement.

On imaging, it showed features of globe indentation and fossa formation, which were suggestive of a pleomorphic adenoma. Furthermore, calcification, as was seen in our case, is very unusual of a lacrimal gland lymphoma.4 As far as we are aware, only two cases of orbital lymphomas with focal calcification have been reported so far in literature.5 Based on the clinical presentation and imaging features, a working diagnosis of pleomorphic adenoma was made. Therefore, an incisional biopsy was not considered and the tumor was excised in toto.

To summarize, this report highlights unusual clinical and imaging features in a case of primary NHL of the lacrimal gland. This entity should be considered in the differential diagnosis of lacrimal gland tumors with similar presentation.



Retreatment of Magnetically Treated Giant Retinal Tear

Abstract We present a case of a 52 years old male where external magnet was used to treat a Giant retinal tear 1

month prior to presentation in our OPD. On examination the vision was perception of light and projection of rays. External magnet was seen sutured to the sclera but fundus examination revealed giant retinal tear with persistent total retinal detachment and proliferative vitreoretinopathy. The patient was taken for surgery twice in our hospital. First the external magnet was removed and two days later he underwent belt buckle, viterectomy, membrane peeling, perflurocarbon liquid, endolaser with silicon oil exchange for giant retinal tear repair. On his last follow up his BCVA was 20/120. Conventional surgery for treating Giant retinal tear is the standard of care in these times and doing other experimental trials on human eyes will worsen the visual prognosis as the timely effective intervention is delayed.

Del J Ophthalmol 2012;22(4):289-290. Key Words : external magnet, giant retinal tear, vitreo-retina, proliferative vitreoretinopathy.

Rhibhu Soni MBBS, MS, Rubina T Soni MS, Preetam Singh MBBS Vipin K Vig MS , Rajbir Singh MS

Magnet therapy has a long history in traditional folk medicine. A commonly held misconception is that magnets attract the iron in blood cells thus moving the blood and stimulating circulation. Negating this theory, a 1991 study on humans found no effect on local blood flow. Tissue oxygenation was similarly unaffected.1,2

We report a case of a 52 years old male who presented to us with an external magnet placed subconjunctivally in the superotemporal quadrant of the right eye which was supposedly used to treat the giant retinal tear. Visual acuity was perception of light and accurate projection of rays at the time of presentation. Anterior segment examination revealed pseudophakia with intraocular pressure of 8 mm Hg by applanation tonometery. Fundus examination revealed a giant retinal tear. He underwent external magnet removal followed two days later by belt buckle, viterectomy, membrane peeling, perflurocarbon liquid, endolaser with silicon oil exchange for the giant retinal tear repair. On his last follow up his BCVA was 20/120 in RE and fundus examination revealed an attached retina.

Case Report

A male patient aged 52 years presented to our Out Patient Department (OPD) with chief complaints of diminution of vision right eye for the past 1 month. He was pseudophakic in both eyes (BE) for the past 10 years

S.B. Dr. Sohan Singh Eye Hospital, Katra Sher Singh, Amritsar Correspondence to : Dr. Rubina T SoniE-mail : [email protected]

with history of extra ocular magnet implant with fluid gas exchange done elsewhere 2 months ago for idiopathic giant retinal tear (GRT) in the right eye (RE). Following surgery the patient did not feel any improvement in vision for which he presented in our OPD.

On examination, the patient had perception of light and accurate projection of rays in the RE. Slit lamp examination (SLE) revealed a small round magnet in a sponge piece sutured subconjunctivally in the superotemporal quadrant of the RE (Figure 1). On fundus examination, a GRT extending from 10 o’ clock to 7 o’clock position in the temporal quadrant with bare retinal pigment epithelium underneath the fold was seen (Figure 2 ).

The patient underwent RE surgery twice in our hospital. First the magnetic sponge was removed (Figure 3)

Figure 1. External magnet in sponge placed subconjunctically

Case Report

Vol. 22, No. 4, April - June, 2012290


under local anaesthesia and he was started on moxifloxacin eye drops. Two days later he underwent belt buckle, viterectomy, membrane peeling, perflurocarbon liquid (PFCL), endolaser with PFCL silicon oil exchange in this eye . On his last follow up his BCVA was 20/120 in RE and fundus examination revealed an attached retina (Figure 4).

Discussion The use of magnets in treatment of intraocular foreign

body removal is well known.3 Experimental use of magnets is being done to treat retinal disorders but till date they are unreliable and not conclusive. An experimental study on animals was found where the use of intraocular and extraocular magnet was done to unfold the retina but it had damaging effects on retina.4 In another study a magnetized encircling scleral buckle and magnetic fluids provided 360° encircling internal tamponade.5 But in the present case a small magnet was placed in the sunconjunctival space in one part over the sclera and it had no beneficial effect in attaching the retina, neither it had any buckling effect.

Conventional treatment of giant retinal tear using external belt buckle, perflurochlorocarbons and silicon oil has better prognostic results as this patient also regained vision after two days of similar surgery. Long term clinical trials are required to know about the basis for such kind of

Figure 2. Giant Retinal Tear (GRT); Figure 3. Removed magnet in sponge; Figure 4. Attached Retina

432

References

1. Stick C, Hinkelmann K, Eggert P, Wendhausen H. Do strong static magnetic fields in NMR tomography modify tissue perfusion ? Rofo 1991; 154(3): 326-31.

2. Charles P, Postow E. Handbook of Biological Effects of Electromagnetic Fields. CRC Press;1996.

3. Mashavekhi A, Siadat F, Moshfegui AA, Peyman GA. Management of magnetic intravitreal foreign bodies in 71 eyes. Ophthalmic Surg Lasers Imaging 2004; 35(5):372-8.

4. Lobel D, Hale JR, Montgomery DB. A new magnetic technique for the treatment of giant retinal tears. Am J Ophthalmol 1978; 85(5):699-703.

5. Dailey J P, Phillips P, C. Lic, Riffle J S. Synthesis of silicone magnetic fluid for use in eye surgery. Journal of Magnetism and Magnetic Materials 1999; 194(3):140-8.

surgery and its long term benefits.

So we conclude that the standard pars plana vitrectomy with PFCL and intra ocular tamponade for treating GRT is accepted form of treatment now-a-days and doing other experimental trials on human eyes worsens the visual prognosis as the timely effective intervention is delayed. This case also emphasizes that such treatments should wait the results of long term experimental trials.



Recent Advances

Pharmacologic Treatment of Atrophic Age Related Macular Degeneration: An update

Abstract Age-related macular degeneration (AMD) is classified into two types wet and dry AMD. Currently, no

drug therapy is available for dry AMD. Newer treatment strategies can be broadly classified in to following categories anti-inflammatory drugs, complement inhibition, trophic factor supplementation, anti oxidant drugs, drugs reducing retinal toxins. These treatment modalities promise to soon find a cure to this disease.

Del J Ophthalmol 2012;22(4):295-299. Key Words : geographic atrophy, age-related macular degeneration, clinical trial

Raghav Gupta MD, FICO, Shorya Azad MS, Abhishek Dave MD, FICO Harsh Inder Singh MD , Sana Tinwala MD

Age-related macular degeneration is the primary cause of blindness and visual disability for adults over 60 years in industrialised countries.1,2 AMD can be classified as wet (neovascular) or dry (atrophic). Although wet AMD constitutes less than 20 % of all AMD cases, it is responsible for the majority (80 %) of the AMD related blindness.3 On the other hand, in dry AMD visual acuity loss occurs gradually over several years, the most severe manifestation being geographic atrophy.4-9 Over the last few years various new treatment modalities have emerged to treat dry AMD. These can be broadly classified as:-

• Anti-inflammatory intervention;

• Complement inhibition;

• Trophic factor supplementation;

• Drugs to prevent oxidative stress;

• Reduction of retinal toxins; and

• Other therapeutic Drugs

Anti-inflammatory InterventionInflammatory mediators have been found in association

with drusens and geographic atrophy. This has created interest in evaluation of various anti-inflammatory agents in dry AMD.

Sirolimus (Rapamycin)

Sirolimus has the ability to inhibit the mammalian

target of rapamycin (mTOR), a serine/ threonine kinase that regulates cell growth, proliferation, motility and survival. Wide therapeutic actions of Sirolimus include inhibiting inflammation, angiogenesis, fibrosis, and hyperpermeability.

Sirolimus also inhibits the translation and activity of hypoxia-inducible factor-1 alpha (HIF-1a), a stress activated protein that mediates the activity of numerous survival proteins involved in angiogenesis and hyperpermeability. Since HIF-1a is a potent vascular endothelial growth factor (VEGF) stimulator; its inhibition affects both VEGF production and activation at the receptor level.10-11

Dose: 20 µl of subconjunctival injection

Glatiramer acetate (Copaxone)

Glatiramer acetate (Copaxone) is an immunomodulatory agent approved for the treatment of multiple sclerosis that induces specific suppressor T-cells and down-regulates inflammatory cytokines. Subcutaneous Glatiramer acetate in patients with dry AMD has shown to reduce the drusen area, eliminate plaque formation and induce neuronal survival.12

Complement InhibitionPolymorphic variants in genes encoding complement

factor H (CFH), complement component 3 (C3), and age-related maculopathy susceptibility 2 (ARMS2) confer significant risks for developing both wet and dry AMD.

There is evidence that the complement cascade plays an important role in AMD pathogenesis, leading to the possibility that complement inhibitors could ‘neutralize’ the response toward inflammatory sites in early AMD13-22.

Dr Rajendra Prasad Centre for Ophthalmic Science, AIIMS, New Delhi- 110029, India Correspondence to : Dr. Raghav GuptaE-mail : [email protected]

Vol. 22, No. 4, April - June, 2012296


POT-4

POT-4 is a derivative of cyclic peptide compstatin. It can inhibit the complement activation system by inhibiting C3, a component upon which all known complement activation pathways converge. POT-4 is designed as an intravitreal gel that functions as a depot, allowing slow and sustained drug release.23

ARC-1905

ARC-1905 is a selective factor C5 inhibitor. This drug is comprised of a chain of nucleic acids called an aptamer. This drug inhibits the cleavage of C5a and C5b, thus blocking downstream complement cascade. C5 is a downstream complement cascade mediator that mobilizes key terminal fragments responsible for tissue pathology: C5a, a proinflammatory fragment, and the membrane attack complex (MAC), which initiates cell lysis and releases pro-angiogenic molecules, such as platelet derived growth factor and VEGF. Unlike monoclonal antibodies, aptamers are synthetic and generally do not elicit an immune response.

Eculizumab/ Soliris

Eculizumab is a recombinant humanized monoclonal IgG antibody derived from a murine anti-human C5 antibody. It is approved by the FDA for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired form of complement induced hemolytic anemia. 24-25 Like ARC-1905, eculizumab binds to the complement protein C5 with high affinity, inhibiting its cleavage to C5a and C5b and preventing terminal complement complex generation.

Trophic factor supplementationNT- 501

Ciliary Neurotrophic Factor (CNTF/NT-501) is a cytokine member of the IL-6 family and a potent neuroprotective agent. CNTF receptors in a device have been identified on Muller glial membranes as well as rod and cone PR. Designated as NT-501, human RPE cells designed to produce neurotrophic factor are encapsulated in an implant measuring approximately 5mm × 1mm with a semipermeable polymer outer membrane.26-46

Brimonidine Intravitreal Implant

Brimonidine is a α-2 receptor agonist. Brimonidine tartrate intravitreal implant is currently available as an ophthalmic solution. The implant delivers the drug to retina for a period of 3 months.47 Brimonidine stimulates the production of neurotrophic factors and has been shown to protect the photoreceptors. Currently implant being used for geographic atrophy is either 200 or 400 µg.

Drugs to prevent oxidative stressAnother strategy for dry AMD focuses on reducing

the oxidative stress of the retina. Interest in the development of antioxidative therapies increased when carboxyethylpyrrole-modified proteins (CEP adducts) were identified in Bruch’s membrane and drusen obtained from AMD tissues. CEP adducts and autoantibodies are also elevated in plasma in those with AMD. CEP modifications are generated by covalent adduction of primary amino groups with an oxidation fragment derived uniquely from phospholipids.48-52

OT-551

OT-551 also known as 4-cyclopropanoyloxy-1-hydroxy-2,2,6,6- tetramethylpiperidine HCl, is a small lipophilic molecule that readily penetrates the cornea when applied as a topical medication. OT-551 is converted by ocular esterases to TEMPOL-H (TP-H), the active metabolite that is a potent free-radical scavenger and antioxidant that does not penetrate the cornea.53 The drug OT-551 was shown to possess anti-inflammatory, antiangiogenic as well as antioxidant properties. OT-551 also was shown to protect against oxidative damage in vitro, to protect against light damage in vivo, to suppress PR cell death in animal models, and to block angiogenesis stimulated by growth factors.54,55

AL-8309A

AL-8309A is a serotonin receptor agonist shown to protect the retina from light damage. It reduces CEP biomarker levels in rat retinas and plasma, and lower CEP autoantibody levels. Because CEP adducts and autoantibodies are elevated in AMD patients, they may be causal in the disease process, making AL-8309A potentially useful in reducing CEP modifications in dry AMD.56 This drug is currently being used as 1% and 1.75% ophthalmic solution.

Reduction of retinal toxinsIt has been seen that in patients of AMD there is an

accumulation of cellular debris, or lipofuscin, within the RPE cells. Lipofuscin is an autofluorescent material composed of lipids, proteins, and vitamin A derivatives that form during daily phagocytosis of photoreceptor outer segments.57

The most abundant autofluorescent compounds in AMD tissues are bisretinoid compounds such as N-retinyl-N-retinylidene ethanolamine (A2E). All-trans retinal (ATR), a retinoid formed in the retina during light exposure, is the precursor for A2E and related molecules. Various therapeutic trials in AMD are directed towards reducing ATR levels, including the one aimed at reducing the rate of retinoid metabolism in the RPE by targeting key visual cycle enzymes.



ACU-4429

ACU-4429 is an orally dosed small non-retinoid molecule that targets RPE. It inhibits the conversion of all-trans-retinyl ester to 11-cis retinol via inhibition of the isomerase, RPE.57 Since it acts as an enzyme inhibitor, it has a longer lasting effect than other drugs which act by reducing the availability of precursor. Dose related side effects are dyschromatopsia and delayed dark adaptation.58 The drug effects on ocular retinoid metabolism can be seen by electroretinography and is well tolerated upto a dose of 75 mg.

Fenretide

Fenretinide is an oral synthetic retinoid derivative which competes with retinol for binding to RBP and cause dose-dependent and reversible reductions in circulating retinol. Fenretide limits the accumulation of toxic retinal fluorophores by preventing the delivery of vitamin A to the RPE, thus downregulating the photoreceptor metabolism. Retinol enters the eye as a ternary complex with retinol binding protein (RBP) and transthyretin (TTR) and is taken into the RPE through a receptor-mediated process. Fenretide is currently being used in doses ranging from 100-300 mg/day for geographic atrophy.

Other Therapeutic Drugs

It has been seen with the help of Doppler flowmetry that blood flow through RPE/ choroid complex is reduced in patients of AMD. This reduction in blood flow in patients of AMD has been found to be more pronounced in patients with increasing severity of AMD. Thus, the drugs which improve choroidal circulation and protect against ischemia may promote survival of photoreceptors and the RPE.

Alprostadil

Alprostadil is a naturally occurring PGE1 with vasodilatory and antithrombotic properties. It was initially approved for the treatment of erectile dysfunction and is currently being used in various vascular disorders. Studies are on to assess if alprostadil can improve choroidal blood flow and improve visual acuity in early geographical atrophy. The drug is delivered as an i.v. infusion over a 15 day period.

MC-1101

It is a topical agent which increases the mean choroidal blood flow. It has been also shown to possess anti- inflammatory and antioxidant properties. Studies have found increased choroidal blood volume and velocity in MC-1101 treated eyes. The most common side effect in these studies was treatment related transitory ocular hyperaemia.

Trimetazidine

This drug is currently approved for the treatment of angina pectoris. It improves myocardial glucose utilisation by stopping fatty acid metabolism and is believed to have cytoprotective effect in ischemic conditions. Ongoing studies are using this drug to slow the conversion of dry AMD to wet AMD. It is available as 35 mg tablet.

Conclusion

As is evident from the above discussion, a large number of investigative therapies have been developed targeting many of the potential pathways implicated in the pathophysiology of Geographic atrophy. Results from ongoing studies are encouraging and show that one or more of these may achieve success over the next few years and provide cure to this important cause of irreversible blindness.

References

1. Zarbin MA. Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol 2004; 122:598–614.

2. Klein BE, Klein R. Forecasting age-related macular degeneration through 2050. J Am Med Assoc 2009; 301:2152–3.

3. Ni Z, Hui P. Emerging pharmacologic therapies for wet age-related macular degeneration. Ophthalmologica 2009; 223:401–10.

4. Martidis A, Tennant M. Age-related macular degeneration. 2nd edn. St. Louis:Mosby; 2004:; pp. 925–933.

5. Anderson DH,MullinsRF, HagemanGS, et al.Arole forlocal inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 2002; 134:411–31.

6. Nozaki M, Raisler BJ, Sakurai E, et al. Drusen complement components C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci U S A 2006; 103:2328–33.

7. Hageman GS, Luthert PJ, Victor Chong NH, et al. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE–Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res 2001; 20:705–32.

8. AREDS. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001; 119:1417–1436.

9. Parodi MB, Virgili G, Evans JR. Laser treatment of drusen to prevent progression to advanced age-related macular degeneration. Cochrane Database Syst Rev 2009; CD006537

10. Yehoshua Z, Rosenfeld PJ, Gregori G et al. Progression of geographic atrophy in age-related macular degeneration imaged with spectral domain optical coherence tomography. Ophthalmology 2011;118:679–86.

Vol. 22, No. 4, April - June, 2012298


11. Sunness JS, Margalit E, Srikumaran D et al. The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials. Ophthalmology 2007;114:271–7.

12. Landa G, Butovsky O, Shoshani J, Schwartz M, Pollack A. Weekly vaccination with copaxone (glatiramer acetate) as a potential therapy for dry age-related macular degeneration. Curr Eye Res 2008;33:1011–3.

13. Yates JR, Sepp T, Matharu BK, et al. Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med 2007; 357:553–61.

14. Wegscheider BJ, Weger M, Renner W, et al. Association of complement factor H Y402H gene polymorphism with different subtypes of exudative agerelated macular degeneration. Ophthalmology 2007; 114:738–42.

15. Vine AK, Stader J, Branham K, et al. Biomarkers of cardiovascular disease as risk factors for age-related macular degeneration. Ophthalmology 2005; 112:2076–80.

16. Sepp T, Khan JC, Thurlby DA, et al. Complement factor H variant Y402H is a major risk determinant for geographic atrophy and choroidal neovascularization in smokers and nonsmokers. Invest Ophthalmol Vis Sci 2006; 47:536–40.

17. Ambati J, Ambati BK, Yoo SH, et al. Age-related macular degeneration:etiology, pathogenesis, and therapeutic strategies. Surv Ophthalmol 2003; 48:257–93.

18. Brantley MA Jr, Fang AM, King JM, et al. Association of complement factor H and LOC387715 genotypes with response of exudative age-related macular degeneration to intravitreal bevacizumab. Ophthalmology 2007;114:2168–73.

19. Despriet DD, Klaver CC, Witteman JC, et al. Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration. J Am Med Assoc 2006; 296:301–9.

20. Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age related macular degeneration. Science 2005; 308:385–9.

21. Haines JL, Hauser MA, Schmidt S, et al. Complement factor H variant increases the risk of age-related macular degeneration. Science 2005; 308:419–21.

22. Scholl HP, Fleckenstein M, Fritsche LG, et al. CFH, C3 and ARMS2 are significant risk loci for susceptibility but not for disease progression of geographic atrophy due to AMD. PLoS One 2009; 4:e7418

23. Ricklin D, Lambris JD. Compstatin: a complement inhibitor on its way to clinical application. Adv Exp Med Biol 2008; 632:273–92.

24. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 2006; 355:1233–1243.

25. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005; 106:3699–709.

26. Bok D, Yasumura D, Matthes MT, et al. Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/peripherin mutation. Exp Eye Res 2002; 74:719–35.

27. Cayouette M, Behn D, Sendtner M, et al. Intraocular gene

transfer of ciliary neurotrophic factor prevents death and increases responsiveness of rod photoreceptors in the retinal degeneration slow mouse. J Neurosci 1998; 18:9282–93.

28. Cayouette M, Gravel C. Adenovirus-mediated gene transfer of ciliary neurotrophic factor can prevent photoreceptor degeneration in the retinal degeneration (rd) mouse. Hum Gene Ther 1997; 8:423–30.

29. LaVail MM, Yasumura D, Matthes MT, et al. Protection of mouse photoreceptors by survival factors in retinal degenerations. Invest Ophthalmol Vis Sci 1998; 39:592–602.

30. Liang FQ, Aleman TS, Dejneka NS, et al. Long-term protection of retinal structure but not function using RAAV. CNTF in animal models of retinitis pigmentosa. Mol Ther 2001; 4:461–72.

31. Liang FQ, Dejneka NS, Cohen DR, et al. AAV-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor survival in the rhodopsin knockout mouse. Mol Ther 2001; 3:241–8.

32. Tao W, Wen R, Goddard MB, et al. Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa. Invest Ophthalmol Vis Sci 2002; 43:3292–8.

33. Aebischer P, Kato AC. Treatment of amyotrophic lateral sclerosis using a gene therapy approach. Eur Neurol 1995; 35:65–8.

34. Sagot Y, Tan SA, Baetge E, et al. Polymer encapsulated cell lines genetically engineered to release ciliary neurotrophic factor can slow down progressive motor neuronopathy in the mouse. Eur J Neurosci 1995; 7:1313–22.

35. Bazan JF. Neuropoietic cytokines in the hematopoietic fold. Neuron 1991; 7:197–208.

36. Helfand SL, Smith GA, Wessells NK. Survival and development in culture of dissociated parasympathetic neurons from ciliary ganglia. Dev Biol 1976; 50:541–7.

37. Varon S, Manthorpe M, Adler R. Cholinergic neuronotrophic factors: I. Survival, neurite outgrowth and choline acetyltransferase activity in monolayer cultures from chick embryo ciliary ganglia. Brain Res 1979; 173:29–45.

38. Stahl N, Yancopoulos GD. The tripartite CNTF receptor complex: activation and signaling involves components shared with other cytokines. J Neurobiol 1994; 25:1454–66.

39. Peterson WM, Wang Q, Tzekova R, et al. Ciliary neurotrophic factor and stress stimuli activate the Jak-STAT pathway in retinal neurons and glia. J Neurosci 2000; 20:4081–90.

40. Wahlin KJ, Campochiaro PA, Zack DJ, et al. Neurotrophic factors cause activation of intracellular signaling pathways in Muller cells and other cells of the inner retina, but not photoreceptors. Invest Ophthalmol Vis Sci 2000; 41:927–36.

41. Beltran WA, Zhang Q, Kijas JW, et al. Cloning, mapping, and retinal expression of the canine ciliary neurotrophic factor receptor alpha (CNTFRalpha). Invest Ophthalmol Vis Sci 2003; 44:3642–9.

42. Fuhrmann S, Kirsch M, Heller S, et al. Differential regulation of ciliary neurotrophic factor receptor-alpha



expression in all major neuronal cell classes during development of the chick retina. J Comp Neurol 1998; 400:244–54.

43. Seydewitz V, Rothermel A, Fuhrmann S, et al. Expression of CNTF receptoralpha in chick violet-sensitive cones with unique morphologic properties. Invest Ophthalmol Vis Sci 2004; 45:655–61.

44. Valter K, Bisti S, Stone J. Location of CNTFRalpha on outer segments: evidence of the site of action of CNTF in rat retina. Brain Res 2003; 985:169–75.

45. MacDonald IM, Sauve Y, Sieving PA. Preventing blindness in retinal disease: ciliary neurotrophic factor intraocular implants. Can J Ophthalmol 2007; 42:399–402.

46. Williams GA, Tao W. A phase II study of encapsulated CNTF secreting cell implant (NT-501) in patients with visual acuity impairment associated with atrophic macular degeneration. 2009. ARVO. Ft. Lauderdale, Fl. Program 5003.

47. Saylor M, McLoon LK, Harrison AR, Lee MS. Experimental and clinical evidence for brimonidine as an optic nerve and retinal neuroprotective agent: an evidence-based review. Arch Ophthalmol 2009;127:402–6.

48. Ni J, Yuan X, Gu J, et al. Plasma protein pentosidine and carboxymethyllysine, biomarkers for age-related macular degeneration. Mol Cell Proteomics 2009; 8:1921–33.

49. Gu X, Sun M, Gugiu B, et al. Oxidatively truncated docosahexaenoate phospholipids: total synthesis, generation, and peptide adduction chemistry. J Org Chem 2003; 68:3749–61.

50. Sayre LM, Sha W, Xu G, et al. Immunochemical evidence supporting 2-pentylpyrrole formation on proteins exposed to 4-hydroxy-2-nonenal. Chem Res Toxicol 1996; 9:1194–201.

51. Ebrahem Q, Renganathan K, Sears J, et al. Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization: implications for agerelated macular degeneration. Proc Natl Acad Sci U S A 2006; 103: 13480–4.

53. Tanito M, Li F, Elliott MH, Dittmar M, Anderson RE. Protective effect of TEMPOL derivatives against lightinduced retinal damage in rats. Invest Ophthalmol Vis Sci 2007; 48:1900–5.

54. Sternberg P, Rosenfeld PJ, Slakter JS et al. Topical OT-551 for treating geographic atrophy: phase II results. Invest Ophthalmol Vis Sci 2010;51:E-Abstract 6416.

55. Wong WT, Kam W, Cunningham D et al. Topical administration of anti-oxidant, OT-551 for the treatment of geographic atrophy: results of a phase I/II clinical trial. Invest Ophthalmol Vis Sci 2010;51:E-Abstract 6418.

56. Renganathan K, Gu J, Collier R, et al. Drugs that prevent retinal light damage impact CEP biomarker levels. 2009. ARVO. Ft. Lauderdale, Fl. Program # 681.

57. Katz ML, Robison WG Jr. What is lipofuscin? Defining characteristics and differentiation from other autofluorescent lysosomal storage bodies. Arch Gerontol Geriatr 2002; 34:169–84.

58. Kubota R, Birch D, David R. Phase 1, dose-escalating study of the safety, tolerability, and pharmacokinetics of ACU-4429 in healthy volunteers. 2009. ARVO. Ft. Lauderdale, Fl. Program # 5009.



Allied Ophthalmic Sciences : Community Ophthalmology

Suman S. Thapa MS, PHD

Abstract Glaucoma is a blinding disease if not treated and is a public health issue of increasing importance. More

than half of glaucoma patients are unaware of the disease until late stages. Glaucoma screening and awareness programs organized over last few years in and around Kathmandu have resulted in increase in identifying undiagnosed glaucoma patients and benefiting individuals who would otherwise not be able to afford treatment.

Del J Ophthalmol 2012;22(4):301-304. Key Words: awareness program, glaucoma week

Nepal Glaucoma Eye Clinic, Tilganga Institute of Ophthalmology,Kathmandu, Nepal Correspondence to : Dr. Suman S. Thapa E-Mail : [email protected]

The Impact of Promoting Awareness, Screening and Patient Education Programs on the

Treatment and Follow up of Glaucoma Patients Attending a Tertiary eye hospital in Nepal

Glaucoma is the second leading cause of visual loss in the world. Quigley estimated that there were 60.5 million people with glaucoma in 2010 and Asians represented 47% of those with glaucoma.1 It has been reported that approximately 50 % of patients with glaucoma were unaware of their condition at the time of diagnosis.2 Studies undertaken in the south Asian region have revealed a poor awareness of eye diseases in the general population.3,4,5 Similarly studies on awareness, knowledge and beliefs on glaucoma in developed countries have also reported that 7-70% of the participants were unaware of glaucoma.6-11

Implementing health care programs in the community and promoting awareness of common eye diseases can bring forth people for an eye examination. This could result in the early diagnosis and treatment of eye diseases and prevention of visual impairment and blindness. Patient education programs in developed countries have been successful in decreasing the morbidity of diseases.12,13 Patient education has also helped improve compliance in glaucoma patients.14

A novel approach to screening and patient education has been adopted by Tilganga Institute of Ophthalmology (TIO) in Nepal to promote awareness, screening and follow up of patients, the results of which are promising.15

MethodsGlaucoma screening and awareness programs

Since 2004, TIO has hosted an annual Glaucoma Awareness Week in either March or April when weather conditions are most favorable for those patients traveling long distances. The event is co-sponsored by the Glaucoma Support Group of Nepal (GSGN) which was founded in 2003 and is a member of the World Glaucoma Patient Association (WGPA). Its members include glaucoma patients and their families, health care providers, and social workers. The objectives of the group are to educate glaucoma patients and their families about the disease, to promote public awareness of glaucoma, and to provide financial support for patients who are unable to afford treatment. During this week glaucoma screening and any necessary treatment are provided free of charge. A comprehensive eye examination is performed, including measurement of visual acuity using a Snellen chart, slit lamp examination, applanation tonometry, and fundus examination with a 90 diopter lens. All glaucoma suspects and newly diagnosed patients subsequently undergo disc photography, optical coherence tomography (OCT), and perimetry. All patients who are newly diagnosed with glaucoma receive counseling from ophthalmic assistants and patient members of the GSGN, are enrolled in the GSGN and Patient Education Program lecture series, and are provided with free samples of medication (typically a topical beta-blocker, made possible in part by donations directly from pharmaceutical companies). Returning patients are also eligible to receive free interval evaluation, medication, and repeated counseling which emphasizes the importance of compliance with therapy.

Vol. 22, No. 4, April - June, 2012302


Patients who have more advanced disease requiring multiple medications or who live far away such that annual follow-up may be prohibitive are scheduled for free surgery (trabeculectomy). Ophthalmic assistants and students have created educational posters about glaucoma, and copies of a patient glaucoma handbook written in Nepali are available for purchase at a reasonable cost with proceeds reinvested in further educational and treatment efforts. The GSGN publishes an annual report summarizing these activities and efforts, and the event has received local television, radio, and newspaper coverage, with patient attendance increasing in each of the years since its inception. Approximately 90% of patients are from Kathmandu and the remaining 10% from villages in or near the Kathmandu valley.

Patient Education ProgramsAnother important educational effort is the Patient

Education Program, comprised of six lectures which take place at TIO on a selected Saturday morning every two months. The series is provided free of charge and is attended by patients and members of the GSGN. Topics presented by ophthalmologists include an introduction to the GSGN, a discussion of glaucoma including risk factors, signs, symptoms, treatment modalities, diagnostic tools used in the diagnosis of glaucoma, instruction on how to properly administer eye drops, possible side effects of glaucoma medications, childhood glaucoma, new advances in glaucoma research, and the sharing of experiences by patients with glaucoma.

At the end of each session attendees who have the financial means are encouraged to make a small donation towards a fund that supports treatment for poor patients throughout the year. Upon completion of the entire Patient Education Program a short quiz is administered, and those individuals who perform satisfactorily are able to become

TABLE 1. Total number of patients examined during the Glaucoma Awareness Week (2004-2011)

TABLE 2. Investigations and treatment supported for those that could not afford



counselors for other glaucoma patients during Glaucoma Awareness Week. The series repeats each year, and starting in 2006 has been broadcast on a local FM radio channel to reach a wider audience.

Results The number of patients examined during the Glaucoma

Awareness Week from 2004- 2011 is presented in the Table 1. From 2004 to 2011 screening at the annual Glaucoma Awareness Week has resulted in the diagnosis of 222 individuals with glaucoma, or 6.6% of total registrants. Attendance has increased annually with a trend toward an increasing number of returning patients (from 145 in 2004 to 247 in 2011). Table 2 presents the number of investigations and treatment supported from the glaucoma fund generated through patient awareness and education programs. The total number of participants during the patient education program is shown in Table 3.

Discussion and ConclusionsGlaucoma is a public health issue of increasing

importance as the global population increases in both age and number. While our limited data show that the programs described above are identifying undiagnosed glaucoma patients and benefiting individuals who would otherwise not be able to afford treatment, an analysis of the effectiveness of educational activities (e.g. through the use of surveys), medication compliance, and long-term visual outcomes is needed to validate this approach. Such data would also be helpful to identify areas for improvement or to suggest different management approaches altogether. For example, interim results from the Collaborative Initial Glaucoma Treatment Study showed that patients randomized to either medical or surgical treatment for

primary open-angle glaucoma had comparable outcomes at five years.16 Such an approach has already been implemented in some parts of India.17

While longer term data is needed before primary surgery can be more broadly recommended, the higher initial cost may ultimately prove to be justifiable in the long run for patients in developing countries who face greater obstacles to accessing health care resources. Similarly, prophylactic laser peripheral iridotomy (LPI) has been studied for the prevention and treatment of PACG in East Asian and Indian populations, though which patients would benefit most from this intervention is still being defined.18-20 Finally, a more current estimate of the prevalence of glaucoma in Nepal is needed (such a study is currently being conducted in the city of Bhaktapur). As mentioned previously, a simple and cost-effective screening plan for glaucoma has yet to be developed, a point emphasized by a 2006 Cochrane review that could not support population-based screening for primary open-angle glaucoma due to the fact that no randomized controlled trials could be identified.21 An analysis of data obtained from the Baltimore Eye Survey failed to demonstrate an acceptable balance of sensitivity and specificity in the study population for several tests (either separately or in combination) commonly used in the diagnosis of glaucoma, including tonometry, stereoscopic fundus photography, and Humphrey visual field analysis.22

In light of the continuing challenges regarding accurate and cost-effective diagnosis of glaucoma in the general population it has been suggested that eye care providers focus their efforts solely on case detection in high-risk individuals (e.g. older age, positive family history, or certain ethnic groups) instead.23,24,25 This is an issue that will continue to evolve as our understanding of glaucoma, as well as diagnostic and therapeutic modalities, are further refined. In developing countries, human resource and

TABLE 3. Graph showing the number of participants during the patient education program (2004-2011)

Vol. 22, No. 4, April - June, 2012304


References

1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006; 90:262-7.

2. Dandona L, Dandona R, Srinivas M, Mandal P, John RK, McCarty CA, Rao GN. Open-angle glaucoma in an urban population in southern India: the Andhra Pradesh eye disease study. Ophthalmology 2000; 107:1702-9.

3. Krishnaiah S, Kovai V, Srinivas M, Shamanna BR, Rao GN, Thomas R. Awareness of glaucoma in the rural population of Southern India. Indian J Ophthalmol 2005; 53:205-8.

4. Sathyamangalam RV, Paul PG, George R, Baskaran M, Hemamalini A, Madan RV, Augustian J, Prema R, Lingam V. Determints of glaucoma awareness and knowledge in urban Chennai. Indian J Ophthalmol 2009; 57: 355-60.

5. Tielsch JM, Sommer A, Katz J, Royall RM, Quigley HA, Javitt J. Racial variations in the prevalence of primary open angle glaucoma - The Baltimore Eye Survey. J Am Med Assoc 1991; 369-74.

6. Gasch AT, Wang P, Pasquale LR. Determinants of glaucoma awareness in a general eye clinic. Ophthalmology 2000;107:303-8.

7. Michielutte R, Diseker RA, Stafford CL, Carr P. Knowledge of diabetes and glaucoma in a rural North Carolina Community. J Community Health 1984; 9:269-84.

8. Elliott AJ. Glaucoma: ignorance and apathy. Eye 1989; 3:485-6.

9. Livingston PM, Lee SE, De Paola C et al. Knowledge of glaucoma, and its relationship to self-care practices, in a population sample. Aust N Z J Ophthalmol 1995; 23:37-41.

10. Attebo K, Mitchell P, Cumming R, Smith W. Knowledge and beliefs about common eye diseases. Aust N Z J Ophthalmol 1997; 25:283-7.

11. Yen MT, Wu CY, Higginbotham EJ. Importance of increasing public awareness regarding glaucoma. Arch Ophthalmol 1996; 114:635.

12. The sixth report of the joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157:2413-46.

13. Cleeman JI, Lenfant C. The national Cholesterol Education Program: progress and prospects. JAMA 1998; 280:2099-104.

14. Zimmerman TJ, Zalta AH. Facilitating patient compliance in glaucoma therapy. Surv Ophthalmol 1983; 28:252-8.

15. Thapa SS, Kelley Kurt H., Rens Van, Poudyal Indira, Chang Lan. A novel approachto glaucoma screening and education in Nepal. BMC Ophthalmol 2008; 26:8- 21.

16. Lichter PR et al. CIGTS Study Group: Interim Clinical Outcomes in the Collaborative Initial Glaucoma Treatment Study (CIGTS) Comparing Initial Treatment Randomized to Medications or Surgery. Ophthalmology 2001;108:1943-53.

17. Thomas R, Paul P, Muliyil J. Glaucoma in India. J Glaucoma 2003;12:81-7.

18. Ang LP, Aung T, Chew PT. Acute primary angle closure in an Asian population: long-term outcome of the fellow eye after prophylactic laser peripheral iridotomy. Ophthalmology 2000;107:2092-96.

19. Lim LS, Husain R, Gazzard G et al. Cataract progression after prophylactic laser peripheral iridotomy: potential implications for the prevention of glaucoma blindness. Ophthalmology 2005; 112:1355-9.

20. Thomas R, Arun T, Muliyil J, George R. Outcome of laser peripheral iridotomy in chronic primary angle closure glaucoma. Ophthalmic Surg Lasers 1999;30:547-53.

21. Hatt S, Wormald R, Burr J. Screening for prevention of optic nerve damage due to chronic open angle glaucoma. Cochrane Database Syst Rev 2006:18:CD006129.

22. Tielsch JM. The epidemiology of primary open-angle glaucoma. Ophthalmol Clin North Am 1991;4:649-57.

23. Tielsch JM, Katz J, Singh K, et al. A population-based evaluation of glaucoma screening: the Baltimore Eye Survey. Am J Epidemiol 1991;134:1102-10.

24. Wilson MR, Khanna S. The value of different screening techniques for glaucoma. Curr Opin Ophthalmol 1994; 5:69-75.

25. Vistamehr S et al. Glaucoma screening in a high-risk population. J Glaucoma 2006;15:534-40.

26. International Agency for the Prevention of Blindness. VISION

infrastructure development are critical to the success of future glaucoma screening and treatment efforts; indeed, the development of such programs is meaningless if a society has neither the manpower nor the equipment and facilities with which to implement them. Nepal has approximately 46 primary eye centers in some of the more remote areas of the country that are staffed by ophthalmic assistants trained to diagnose and treat minor eye diseases and refer patients to one of the 18 larger district eye hospitals when necessary. It is crucial that these providers are adequately trained in the diagnosis and effects of glaucoma as they may represent the only opportunity for case detection and education in their respective regions. TIO has previously conducted a glaucoma training workshop for ophthalmic assistants and continues to look for ways to improve such programs, as well as to expand training to include general ophthalmologists from the district eye hospitals where similar programs for screening, treatment, and education may be implemented if proven effective. Due in part to some of the challenges discussed above, glaucoma was not included as an avoidable cause of blindness in the VISION 2020 initiative, launched jointly in 1999 by WHO and the International Agency for the Prevention of Blindness (IAPB).26

Thus, it is incumbent upon eye care providers and public health officials to ensure that glaucoma remains a priority along with other more easily identifiable and treatable eye diseases. It is our hope that this task will be accomplished in part through the continued development, refinement, and validation of sustainable clinical and educational programs such as those described here.



Brief Communication

A unusual case of Self Inflicted Multiple Needles Injuries to both eyes

Shweta Gaur MS, HK Bisht MBBS

Self-mutilation, the deliberate destruction or alteration of body tissue1 without conscious suicidal intent, occurs in a variety of psychiatric disorders. Major self-mutilation includes eye enucleation, limb and genital injury. Minor self-mutilation includes self-cutting and self-biting. Self-mutilators usually have a motive. For some, the goal is the internal relief of tension, while for others the goal is external, with an obvious secondary gain. Biological theories2 include disorders of serotonergic, dopaminergic, and opiate neurotransmitters. Management3 of self-inflicted eye injury requires close cooperation between ophthalmologists and psychiatrists as well as other medical specialists, to ensure quick resuscitation of the patient, prompt diagnosis and treatment4 of any injuries, and treatment of the underlying behavior that led to the injuries. Eye –injuries assume importance as they are vision-threatening and of great medico-legal significance. We report a case of 23 year old male presented in the eye department for removal of tailoring needles from both lids and adjoining area. He was apparently

alright two month back then he developed headache which was not associated with vomiting and fever. Headache was severe and throbbing in nature and present throughout the day. He took some local medications but did not get any relief. Then he consulted physician who advised him for acu-puncture. The treatment was very expensive that was not affordable to him. So, he inserted ten simple tailoring needles himself; one in a day, four needles under the skin of middle of forehead, two under the skin of upper lid of right eye, two under the skin of upper lid of left eye and two under the skin of the lateral side of left eye. He got significant relief with that. There was a past history of intravenous heavy dose steroid infusion for making his built. On examination he was alert and his vital signs were stable. There was no neck stiffness. His systemic examinations were unremarkable. He was oriented to time, place and person. He was attentive with ill-sustained concentration with delusional belief and impaired judgment. Psychiatric examination confirmed him a patient of schizophrenia. X-Ray both AP and Lateral view (Figure 1

Upgraded Department of Ophthalmology & PsychiatryS.N. Medical. College, Agra Correspondence to : Dr. Gaur ShwetaE-mail : [email protected]

Figure 1. X -ray lateral view showing multiple needles Figure 2. X - ray AP view showing multiple needles

& 2 ) revealed multiples needles. His electroencephalogram, Contrast Enhanced CT and thyroid function test were normal. The needle was removed under general anesthesia by making small incision near entry of all needles. He was given behavior therapy to prevent him from inflicting self injuries. Self-injury is a term often used to mean the same

Vol. 22, No. 4, April - June, 2012306


things 5 as self-harm or self-mutilation. Essentially, it involves the act of injuring or causing pain to one’s own body. Types of self-injury can range from something relatively minor (in terms of degree of harm) such as picking one’s skin, superficial cutting, or pulling out hair, to something more serious or dangerous like deep cutting or amputating part of one’s own body. When a person with schizophrenia engages in self-injury, it often involves something rather bizarre and potentially very serious. Self-mutilating behavior has been studied in a variety of racial, chronological, ethnic, gender, and socioeconomic populations. People who participate in self-injurious behavior are usually likeable, intelligent, and functional. At times of high stress, these individuals often report an inability to think, the presence of inexpressible rage, and a sense of powerlessness. Self-injury6 can be prevented by timely interventions, it almost always occurs during florid psychosis. One must rule out all possible organic causes before making the diagnosis of self-injury. Once concluded however, prompt intervention by a multi-pronged approach of cooperation between doctors can help the patient. Psychiatric evaluation allows for diagnostic evaluation, understanding of the drives and psychoses that have driven the patient to such extreme actions, and the instigation of immediate treatment. This treatment may take the form of neuroleptic medication, antidepressants, and above all close observation, to ensure there are no further

References

1. Favazza AR. The coming of age of self-mutilation. J Nerv Ment Dis 1998; 186(5):259–68.

2. Yang HK, Brown GC, Magargal LE. Self-inflicted ocular mutilation. Am J Ophthalmol 1981;91(5):658–63.

3. Tapper CM, Bland RC, Danyluk L. Self-inflicted eye injuries and self-inflicted blindness. J Nerv Ment Dis 1979; 167(5):311–4.

4. Stannard K, Leonard T, Holder G, Shilling J. Oedipism reviewed: a case of bilateral ocular self-mutilation. Br J Ophthalmol 1984; 68(4):276–80.

5. Rogers T. Self-inflicted eye-injuries. Br J Psychiatry 1987; 151:691–93.

6. Rosen DH, Hoffman AM. Focal suicide: self-enucleation by two young psychotic individuals. Am J Psychiatry 1972; 128(8):1009–12.

episodes of any self-destructive behavior. All patients will require long-term follow-up of their condition. There is some evidence to suggest that selective serotonin uptake blockers may help influence future self-mutilator behavior. The prognosis varies depending upon a person’s emotional or psychological state. It is important to determine the factors that lead an individual’s self-injuring behaviors. It also is important to identify any pre-existing personality disorders that need to be treated.

Announcement Delhi Journal of Ophthalmology

The Best “Original article” published in the Delhi journal of ophthalmology in a calender year will be awarded in the DOS Annual Conference.

Editorial Office

Dr.Rajesh Sinha

Editor, DJO & Associate Proff.of OphthalmologyRoom. No. 479, Dr.R.P. Centre for Ophthalmic Sciences,

AIIMS, Ansari Nagar, New Delhi - 110029



Brief Communication ; Letter to editor

Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences, New Delhi

References

1. Wolf EJ, Braunstein A, Shih C, Braunstein RE. Incidence of visually significant pseudophakic macular edema after uneventful phacoemulsification in patients treated with nepafenac. J Cataract Refract Surg 2007; 33:1546–9.

2. Miyake K, Ota I, Miyake G, Numaga J. Nepafenac 0.1% versus fluorometholone 0.1% for preventing cystoid macular edema after cataract surgery. J Cataract Refract Surg 2011; 37:1581–8.

3. Congdon NG, Schein OD, von Kulajta P, Lubomski LH, Gilbert D, Katz J. Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs. J Cataract Refract Surg 2001; 27:622–31.

Mayank Bansal MBBS

Dear editor,The original article on “A Comparative Study of Topical Dexamethasone 0.1% and Topical Nepafenac 0.1% Ophthalmic

Solutions in Cataract Patients Undergoing Manual Small Incision Cataract Surgery” was extremely practical and informative in terms of usage of a new treatment modality for a condition encountered by all of us regularly. Undoubtedly the comparison of the more established topical steroids with topical non-steroidal inflammatory drugs (NSAIDS) has been a topic of debate and research for many years, with renewed interest with the introduction of nepafenac. To add to the comparison described in this study, previously published article by Wolf et al1 in 450 patients, has compared the efficacy of prednisolone and nepafenac-prednisolone combination in controlling visually significant macular edema after phacoemulsification. They found a higher incidence of visually significant pseudophakic macular edema in patients treated with prednisolone alone and hence supported the use of nepafenac-prednisolone combination.

Furthermore, in a subsequent study by Miyake et al2 in 59 patients, comparing nepafenac with low potency steroid, fluorometholone, former was found to be more effective in preventing cystoid macular edema (CME) and resulted in more rapid visual recovery. Hence, they recommended the routine use of nepafenac post cataract surgery. Though we need to be aware of potential side effects of topical NSAIDS which include mild ones, such as transient burning, stinging, and conjunctival hyperemia, as well as severe ones, such as toxic keratitis and corneal melting.3 Perhaps documenting visual acuity and macular edema in this original article, would add to the most clinically relevant aspects to our knowledge.



Photo Essay

Epithelial Tumors of Lacrimal Gland - Management Pearls

Guru Nanak Eye Centre, Maulana Azad Medical College

Correspondence to : Dr. Ruchi GoelE-mail : [email protected]

Ruchi Goel MD, DNB, FICS, Saurabh Kamal MS, DNB, FICS, Sonam Angmo Bodh MS, DNB, FICS, Sushil Kumar MD Smriti Nagpal MBBS, Ksitij Aditya MBBS, Smriti Bansal MBBS, Puja Sakhuja MD

Among the expanding lesions of the lacrimal gland, 50% originate from the epithelial elements of which 50% are pleomorphic adenomas, 25% are adenoid cystic carcinomas and the remaining 25% are comprised of myoepitheliomas, oncocytoma, Warthin’s tumor, primary adenocarcinoma, pleomorphic adenocarcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, squamous cell carcinoma, malignant myoepithelial carcinoma and carcinosarcoma.1 Proper differentiation between the epithelial malignancies and inflammatory lesions is mandatory because of the life threatening nature of the former which may target the young

Figure 1: Clinical photograph showing superolateral mass of right orbit with non axial proptosis inferomedially; Figure 2: CT scan of orbit showing a well circumscribed mass; Figure 3: Ultrasound B scan suggestive of an encapsulated mass; Figure 4: Lateral orbitotomy for removal of the tumor; Figure 5: Gross appearance of the tumor showing bosselations; Figure 6: Histopathologic appearance of LGPA; Figure 7: Clinical photograph showing superolateral mass of left orbit with displacement of the globe inferomedially; Figure 8: Coronal section of the CT scan; Figure 9: Sagittal section of CT scan. Figure 10: Anterior orbitotomy to remove the tumor; Figure 11: Gross appearance of the tumor ; Figure 12: Microscopic picture of the ACC of lacrimal gland.

population. Even benign tumors if inadequately removed can turn malignant. Subacute presentation of short duration (usually 4-6 months) and radiographic evidence of infiltration of adjacent structures, calcification and irregular erosion and destruction of bone are suggestive of malignant epithelial neoplasms but a typical presentation may be missing and features may overlap which happened in our patients.

Case 1

A 24 year old male presented with downward and medial proptosis and painless progressive diminution of vision of right eye for the past 8 months. On examination, the best corrected visual acuity (BCVA) in the right eye was 6/12, the globe was displaced 6 mm anteriorly, 8 mm inferiorly and 4 mm medially, with restriction in right dextroelevation (Figure 1). A firm mass was felt in superolateral orbit with no change on valsalva or with change of head position. The

1 2 3 4

5 6 7 8

9 10 11 12

Vol. 22, No. 4, April - June, 2012312


pupillary reactions, corneal and periorbital sensations were normal. The disc was normal and there were retinochoroidal folds in the macular region. The left eye was normal. CT scan showed a well defined soft tissue lesion in extraconal superolateral compartment 2.5 × 2.7 × 1.7 cm with post contrast enhancement, bony excavation and displacement of a globe inferomedially (Figure 2). The Ultrasound B scan (Figure 3) as well as the CT scan were suggestive of provisional diagnosis of cavernous haemangioma. The mass was removed en bloc by lateral orbitotomy (Figure 4). Grossly, the mass was pseudoencapsulated with bosselations projecting from the surface (Figure 5). Histopathologically, the tumor was well circumscribed, with pseudocapsule, composed of ductal epithelial cells, surrounded by myoepithelial cells, embedded in a chondroid matrix and absence of nuclear atypia and the overall features were suggestive of lacrimal gland pleomorphic adenoma (LGPA) (Figure 6). Due to its anterior location, the LGPA may be misdiagnosed as a hematoma, dermoid, sebaceous cyst or a dacryops.2 In our patient an incorrect diagnosis of cavernous hemangioma had been made. The management of LGPA is based on accurate history supported by radiographic features and requires en bloc removal of mass within its pseudocapsule. In atypical cases, an incisional biopsy may be indicated. The accepted clinicoradiological criteria used for the diagnosis of LGPA have a high false-positive rate, even in experienced hands.3 An incisional biopsy may reduce unnecessary lacrimal gland excision in false positive cases but can increase the risk of tumor seeding in LGPA. Recurrent LGPA tends to develop multifocally and may be widespread in the operative field with potential lifelong risk of malignant transformation.4

Covering the incision site with butyl-2-cyanoacrylate which serves as an extension of tumor capsule has been suggested to prevent seeding in LGPA.

Case 2

A 22 year old female presented with diminution of vision and progressive mass in the left orbit for the past 2 years which had become painful since 2 months. On examination, the BCVA in the left eye was 4/60. In the left orbit, a hard mass 3.5 × 2.5 cm was felt superolaterally pushing the globe inferiorly by 12 mm and medially by 4 mm (Figure 7). There was restriction of left eye on laevoelevation. There was a relative afferent pupillary defect in the left eye. The corneal and periorbital sensations were normal. Fundus examination of the left eye revealed a hyperaemic disc with blurred margins and choroidal folds. The right eye was normal. There was no lymphadenopathy. An incision biopsy was performed which was suggestive of adenoid cystic carcinoma (ACC) of lacrimal gland. Haemogram, liver function tests were normal. CT scan showed a well defined 3.1 × 2.1 cm heterogeneously enhancing mass in the superolateral orbit with no bony abnormality or soft tissue calcification (Figure 8 & 9). There was no intracranial extension. There was no lesion in chest or abdomen. An orbital exentration was advised, for which the patient did not consent. Thus, a globe sparing approach with local excision of the mass through anterior orbitotomy

(Figure 10) followed by external beam radiation was planned.Grossly, a mild encapsulated tumor seen (Figure 11). Histopathologically it displayed cribriform and glandular architecture. The cells were moderately eosinophilic with cell nests and islands separated by fibrocollagenous stroma. Pseudocysts filled with eosinophilic to basophilic material were seen. Mitosis and perineural invasion was present. The diagnosis of adenoid cystic carcinoma was confirmed (Figure 12). The optimal local therapy for ACC of lacrimal gland confined to the orbit ranges from local surgical approach to radical multidisciplinary intervention. Despite extensive surgery and radiation therapy the survival outcomes are dismal with survival rate of less than 50% at 5 years.1 A recent study advocates an orbitocranial approach with removal of orbital bone to obtain adequate margins followed by postoperative irradiation to achieve excellent local and regional control rates for ACC of the lacrimal gland, although patients continue to remain at risk of long-term distant metastases.5 The main cause of death is due to intracranial spread which is hastened by perineural invasion.6

In patients at high risk of recurrence, concomitant platinum-based chemotherapy may be added to postoperative radiotherapy in an attempt to enhance radio-sensitivity. While encouraging responses have been reported with intra-arterial neoadjuvant chemotherapy, this strategy is associated with substantial toxicity.7 Proton beam therapy, holds promise of hope for these patients. It allows delivery of lethal doses to the tumor bed and along the predicted perineural spread because of its extremely accurate focussing.6

References

1. Tse DT, Hui JI. Epithelial tumors of lacrimal gland. In:Jakobiec A, Principles and practice of Ophthalmology. Third edition. USA: Elsevier;2008, 2977-86.

2. Murphy MB, Rodriques MM. Benign mixed tumor of the (palpebral) lacrimal gland presenting as a nodular eyelid lesion. Am J Ophthalmol 1974; 77:108-11.

3. Prabhakaran VC, Cannon PS, McNab A, Davis G, O’Donell B, Dolman PJ, et al. Lesions mimicking lacrimal gland pleomorphic adenoma. Br J Ophthalmol 2010;94(11):1509-12.

4. McNab AA, Satchi K. Recurrent lacrimal gland pleomorphic adenoma: clinical and computed tomography features. Ophthalmology 2011;118(10):2088-92.

5. Wilson KF, Ward PD, Spector ME, Marentette LJ. Orbitocranial approach for treatment of adenocystic carcinoma of the lacrimal gland. Ann Otol Rhinol Laryngol 2011;120(6):397-400.

6. Sutula FC. Tumors of lacrimal gland and sac. In:Jakobiec A, Principles and practice of Ophthalmology. Third edition. USA: Elsevier;2008, 2987-3004.

7. Le Tourneau C, Razak AR, Levy C, Calugaru V, Galatoire O, Dendale R, et al. Role of chemotherapy and molecularly targeted agents in the treatment of adenoid cystic carcinoma of the lacrimal gland. Br J Ophthalmol 2011;95(11):1483-9.



Industry News

HOYA Corporation

Preloaded iMICS1 lenses (251 & 250 model)

HOYA is introducing unique IOL design iMics1 in preloaded iSert Platform which redefines the standard for safety, quality & efficiency in IOL.

Preloaded lenses are completely enclosed from manufacture to implantation, preventing toxic anterior segment syndrome and other forms of contamination stemming from reusable materials and inadequate sterilization.

Ø Fully Preloaded implantation System at 2.2 mm with Hydrophobic Monoblock IOL:-

• For Safe, Reliable & efficient minimal Invasive surgery

Key highlights are

Ø Easy implantation by one –step technique:-

• Controlled unfolding of haptic and excellent centration.

Ø Preloaded with Proven iMics1 IOL:-

• Unique Haptic Tips enable good visibility

• Hybrid Monoblock construction

• Sharpest Edge design

• HOYA Aspheric Balanced Curve (ABC) Design



Authorship responsibility, Disclosure and Copyright transfer

Manuscript title (including all supplementary digital content such as tables, diagrams, figures, photo-graphs, flow charts, videos, etc) : ____________________________________________________________________________________________________________________________________________________________________________________________________________________

Manuscript type: Original article Case report Technique Photoessay Review Brief Communication Allied Ophthalmic Sciences Recent Advences

Corresponding Author (Full name with designation details) : ____________________________________ ____________________________________________________________________________________________________________________________________________________________________________Complete Mailing Address: _______________________________________________________________ Email ID: _____________________________________________________________________________Telephone / mobile number / Fax: __________________________________________________________I, ___________________________________________ on behalf of all my co-authors of the manuscript entitled _____________________________________________________________________________________________________________________________________________________________________declare that the submitted work is original and does not infringe upon any copyright. I guarantee that this work does not contain any material that is libelous / contentious. The authors accept full responsibility for the views expressed in the manuscript and hereby give consent for its publication in the Delhi Journal of Ophthalmology (both print and electronic media). The authors hereby also identify any financial interests, affliations to institutions/organizations/companies relavant to the manuscript.

Financial Disclosure / Conflict of Interest: ___________________________________________________(Write None if there is no financial interest)Signature: _____________________________________________________________________________Date & Place: __________________________________________________________________________


The corresponding author is required to sign the authorship responsibility, disclosures and copyright transfer form on behalf of all authors and send in the signed form ( by fax or email) to the Editor, Delhi Journal of Ophthalmology, Room No 479 4th Floor, Dr R P Centre, AIIMS, Ansari Nagar, New Delhi 110029. [email protected] SinhaEditorDelhi Journal of Ophthalmology

Vol. 22, No. 4, April - June, 2012316


Delhi Journal of Ophthalmology accepts articles which are original and not being considered for publication in any other journal. All submitted manuscripts are subject to review by independent experts in the field. You may submit your manuscripts with a covering letter to the Editor of the journal.

Manuscript SubmissionAt Delhi Journal of Ophthalmology, we are soon

starting the online submission of manuscript, the information regarding which will be soon provided in DOS times, DJO and the website of DJO and DOS. Till date we have managed our relationship with authors on a personal level and authors have been sending their manuscript by e-mail to the editorial office.

Editorial policyDelhi Journal of Ophthalmology endorses the Uniform

Requirements for Manuscripts Submitted to Biomedical Journals, issued by the International Committee for Medical Journal Editors, and Code of Conduct for Editors of Biomedical Journals, produced by the Committee on Publication Ethics.

Author disclosure, copyright transfer & con-flict of interest policy

Authors are responsible for the content of material and views expressed in the manuscripts. Authors must state explicitly whether potential conflicts do or do not exist (e.g. personal or financial relationships that could influence their actions) and any such potential conflict of interest (including sources of funding) should be summarized in a separate section of the published article.

Details of relevant conflicts of interests (or the lack of) must be declared in the ‘Disclosure’ section of the manuscript. The corresponding author of articles accepted for publication, will be required to send us a signed copyright transfer form on behalf of all the authors.

Policies on ethical conduct of research where articles include publication of original data related to human or animal experimental investigations, appropriate institutional review board approval is required and should be described within the article. For those investigators who do not have formal ethics review committees, the principles outlined in the Declaration of Helsinki should be followed. In attempting to maintain patient anonymity, identifying details should be omitted where they are not essential. However, patient data should never be amended or falsified. Informed consent should be obtained whenever there is any doubt regarding assurance of anonymity.

Preparation of ManuscriptManuscripts of the following types may be submitted:

o Major Review

o Original Article

o Techniques

o Case Reports

o Recent Advances

o Allied Ophthalmic Sciences

o Photo Essay

o Brief Communication

All types of articles should include the

following: • Forename(s) and surnames of authors

• Author affiliations: department, institution, city, state, country

• Abstract: 200- 250 words; Structured only in Original Article

• 3–4 keywords

• Running header (shortened title)

• Corresponding author: name, address, phone, fax, email

• Original Article to be prepared under following headings Introduction Methods Results Discussion References and acknowledgements Legends for display items (Figures and Tables)

• Tables and figures to be quoted in text as superscript in order of appearance

• The preferred electronic format for text is Microsoft Word

• Spell out acronyms in the first instance of appearance in the abstract and paper

• Word counts: Major Review and Original article: 3000- 4000 words

Techniques and Recent Advances: 1000- 1500 words

Information for Authors



Case Reports and Photo Essay: 750 – 1000 words

• Suppliers of drugs, equipment, and other brand-name material are to be credited in parentheses (company, name, city, state, country)

• All articles to be referenced in accordance to the Vancouver format.

• Figures and Tables are to be submitted as separate files. They are to be numbered in the sequence of appearance in the text, with a descriptive heading/ legend provided for each. Abbreviations and footnotes are to be placed immediately below the table. Figures are to be submitted as JPG/ TIFF files, or in their originating graphics application.

• Graphics/ contents downloaded from web pages are NOT ACCEPTABLE.

All original articles are subject to peer review and editorial approval.

Contact Details: For further queries about your contribution, please contact:

Dr Rajesh Sinha MD, DNB, FIACLE, FRCSEditor, DJO

& Associate Professor of OphthalmologyRoom No.479, 4th Floor,

Dr. R. P. Centre, AIIMS, New DelhiE-mail: [email protected]

issn 0972-0200 vol.22, no.4, april - june, 2011 delhi ... · 295. pharmacologic treatment of...

Documents