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4 April 2011

Posner-Schlossman Syndrome Glaucomatocyclitic Crisis

John R. Martinelli, OD, FAAO St. Georgeʼs University School of Medicine

Abstract Posner-Schlossman syndrome (PSS) or Glaucomatocyclitic Crisis is an infrequent and typically unilateral, recurrent, inflammatory, open-angle ocular hypertensive disorder. The condition normally affects individuals between 20 – 50 years of age and has no racial or sexual predilection. PSS is marked by an acute marked elevation of intraocular pressure (IOP) associated with mild uveal inflammation. The uveitis and symptoms at the initial presentation may be negligible and care must be taken when considering differential diagnoses. Medical treatment is indicated to control inflammation and lower intraocular pressure thereby preventing secondary glaucomatous optic nerve damage and vision loss. Associated systemic conditions may be absent; however, generalized inflammatory and auto-immune etiologies should be investigated. Keywords: Glaucoma, Glaucomatocyclitic Crisis, Inflammatory Glaucoma, Inflammatory Disease, Posner-Schlossman Syndrome, PSS, Uveitis, Uveitic Glaucoma

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Introduction Posner-Schlossman syndrome (PSS), inflammatory glaucoma, uveitic glaucoma, or glaucomatocyclitic crisis are terms used in the diagnosis of ocular inflammatory disease contributing to increased intraocular pressure (IOP) with the risk of associated glaucomatous optic nerve damage. Often, the IOP rise can be quite dramatic ranging upwards from 40mm Hg to 60mm Hg.1 Of course, IOP at this level can and will create a pressure related secondary optic neuropathy and visual field defect if not treated promptly and appropriately. First explained in 1813, Joseph Beer suspected an association between uveitis and glaucoma and described it as an arthritic iritis followed by glaucoma and loss of vision.2 In 1891, Priesley Smith proposed a modern classification of uveitic glaucoma.2 Specific forms of uveitic glaucoma were described by Fuchs in 1906 including heterochromic uveitis.2 In 1948, Posner and Schlossman coined the term glaucomatocyclitic crisis.2 Worldwide, PSS is considered rare and is primarily found to be a unilateral disorder; however, several bilateral cases have been described in the literature.4,7,8 Very often the etiology is unknown or idiopathic; however, associations with systemic conditions such as the herpes virus, HLA-Bw54 defect, peptic ulcer, allergy, and others have been described.1,5 Historically, there appears to be some discrepancy in the literature whether “true” PSS can be associated with systemic disease or if it is indeed purely an idiopathic primary ocular condition. The actual diagnosed glaucomatocyclitic event may be one of many undetected exacerbations over time being that patient symptoms can be mild and thus sub-clinical.1,3,5,9 Regardless of etiology, the ocular manifestations must be treated aggressively to prevent the potential additive effects of this condition on ocular tissue and the optic disc. Additionally, various ocular differential diagnoses should be considered such as inflammatory open-angle glaucoma, acute angle-closure glaucoma, mixed mechanism glaucoma, neovascular glaucoma, pigmentary glaucoma, Fuchs heterochromic iridocyclitis, and herpes simplex or zoster keratouveitis. Case Report A 66 year old Caucasian woman presented to our center for the first time on January 15th, 2007 with a chief complaint of recent blurred vision and mild achiness of her right eye, of two days duration. She denied any previous similar episodes and reported an otherwise unremarkable ocular history. Her systemic history was significant for hypertension, osteoporosis, and osteoarthritis controlled with Lotrel 5/20 (Amlodipine/Benazepril), Actonel (Risedronate), Evista

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(Raloxifene), and Piroxican. She denied any breathing difficulties. She reported an unremarkable systemic and ocular family history. Her uncorrected VA was 20/60 PH 20/50 OD, 20/40 PH 20/NI OS. Pupils were unequal OS > OD with increased asymmetry in dim illumination. There was no evidence of ptosis OU or facial anhydrosis. Versions were full and unrestricted without subjective symptoms of diplopia. Confrontation visual field showed a slight generalized 360 degree constriction OD but was full OS. Biomicroscopic examination OD revealed slight episcleral injection with grade II stromal corneal edema and associated descemet folds. There was early inferior EBMD present. Trace fine keratic precipitates were evident on the corneal endothelium. Grade I anterior chamber cells and flare were present. A partial posterior synechia was evident in the inferior and nasal quadrant creating the anisocoria. Early to mild nuclear sclerotic and cortical lens changes were apparent. The angle remained open, grade III by Vonherrick technique, with some slight nasal narrowing secondary to the synechia creating an anterior step approach of the iris. Applanation intraocular pressure was 52mmHg OD and 10mmHg OS. Although difficult through a mildly edematous cornea, Goldmann 3-mirror gonioscopy was performed showing grade I trabecular pigment without evidence of exfoliative material or peripheral anterior synechia in any of the four quadrants. All angle structures including schwalbeʼs line, trabecular meshwork, schlemmʼs canal, and scleral spur were successfully observed with the ciliary body being the deepest visible structure. The inferior and nasal quadrants did appear slightly narrow due to the posterior synechia and slight iris step; however, all angle structures remained in view without evidence of secondary pupillary block angle closure. There was no evidence of iris transillumination or iris neovascularization. Through the hazy cornea and lens changes, dilated 90 D evaluation demonstrated a healthy appearing optic disc with healthy rim tissue and a 0.3/0.2 C/D. Vitreous, peripheral retina, posterior pole, vessels, and macula were unremarkable. There was no evidence of vitreous cells, vasculitis, or posterior inflammatory disease such as peripheral pars planitis. Biomicroscopic examination OS was completely unremarkable aside from the early to mild nuclear and cortical lens changes. There was no evidence of anterior inflammatory disease with an open and quiet anterior chamber. Dilated 90D evaluation revealed a healthy optic disc and rim tissue with a 0.2/0.2 C/D. Vitreous, peripheral retina, posterior pole, vessels, and macula were unremarkable. There was no evidence of vitreous cells or posterior inflammatory disease. The reduced uncorrected pinhole acuity was attributed to the presenting condition as well as mild lens changes apparent in each eye. Considering the obvious pathology present and patient discomfort, refraction and keratometry was deferred until resolution or stability of the corneal edema and inflammation

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became clinically evident. For the same reason, color vision and stereopsis was to be performed subsequently. The delineating characteristics of inflammatory open angle glaucoma or uveitic glaucoma and Posner-Schlossman syndrome as defined in the literature reveals two separate entities. PSS is marked by significantly elevated IOP in the presence of negligible to mild inflammation.1,3,5 Inflammatory glaucoma can present with dramatic uveitic conditions including significant episcleral injection, excessive cell and flare, moderate keratic precipitates, posterior and anterior synechia, and pain.2 The evaluation, treatment, systemic considerations, and follow-up care are similar although inflammatory glaucoma is more likely to be found with systemic contributors.2 PSS is somewhat paradoxical being a typically cyclic condition but more likely to be idiopathic without a known etiology.1,3,5,9 Therefore, a treatment plan of the following was prescribed with a scheduled 1 day follow-up: Pred-Forteʼ (Prednisolone Acetate 1%): 1 gtt Q2H OD Homatropine 5%: 1 gtt Q12H OD CoSopt (Dorzolamide 2%/Timolol 0.5%): 1 gtt Q12H OD Alphagan P (Brimonidine 0.15%): 1 gtt Q12H OD The avoidance of a prostaglandin agonist in the treatment must be noted and is of significance so to not enhance the inflammatory cascade. Optic disc HRT, photos, and 30-2 threshold visual fields were scheduled. Bloodwork including CBC with differential, SMA-20, ANA, ESR, RF, ACE, and HLA-B27 was ordered. A chest XR was also requested.

Figure 1.1 Figure 1.2

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Figure 1.3 Follow-up #1 She returned the next day as scheduled for follow-up. Uncorrected VA was unchanged at 20/60 PH 20/50 OD. OS was unremarkable. OD biomicroscopic evaluation was relatively unchanged with persistent stromal corneal edema and descemet folds, trace KPʼs, mild anterior chamber cells and flare, as well as the partial nasal posterior synechia and slight anterior iris step. The synechia was still apparent despite the initial homatropine treatment which had now created a resultant mydriatic ovoid pupil. The angle remained open. Fortunately, however, the intraocular pressure dropped dramatically to 8mmHg. Considering the rapid reduction of IOP, she was instructed to continue the medical treatment regiment as prescribed. It was stressed that complete resolution of this episode may take from days to weeks and that she would require a slow taper of the treatment. She was advised of the possible need for oral steroid treatment if the topical regiment proved to be inadequate. She was also explained of the possibility of an extended maintenance period on the topical steroid in the case of prolonged inflammatory activity. Pending her lab results, an appropriate referral would be made. She was asked to return for follow-up in 4 days. Follow-up #2 She returned as scheduled for her 4 day follow-up visit showing a marked improvement. The left eye continued to be unremarkable. The uncorrected VA OD was stable 20/60 but now with improved 20/30 PH acuity. IOP remained controlled at 8mm Hg. Significant resolution of the corneal edema and folds was apparent as well as a reduction of the anterior chamber reaction. Trace - grade I stromal corneal edema with trace descemet folds were viewed along with trace – grade I cell and flare in the anterior chamber. Keratic precipitates were absent. However, the nasal posterior synechia and associated iris step continued to remain unchanged within an open anterior chamber. Hoping to also break the synechia, the treatment was continued for an additional 5 days.

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Figure 2.1 Figure 2.2 Follow-up #3 She returned as scheduled for her 5 day follow-up visit with continued improvement. Corrected VA with her current spectacle prescription was 20/30 OU without PH improvement. The left eye was again unremarkable. OD IOP rose slightly to 15mm Hg. The previous corneal edema with descemet folds was totally resolved. One cell was viewed in the open anterior chamber. There was now no evidence of persistent posterior synechia or iris step. A mydriatic pupil was apparent from the Homatropine therapy; however, an ovoid pupil remained. Nasal anterior lens capsule pigment dusting was observed secondary to the broken synechia. She was instructed to discontinue Homatropine and Alphagan, taper the Pred-Forte to QID, and continue the Cosopt Q12H. A 1 week follow-up was scheduled.

Figure 3.1 Figure 3.2 Follow-up #4 She returned as scheduled for her 1 week follow-up. Corrected VA was stable at 20/30 OU. The left eye was unremarkable. A slight ovoid pupil remained evident OD without posterior synechia. IOP was 10mm Hg. There was no evidence of continued ocular inflammatory disease. Trace pigment dusting of the nasal

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anterior lens capsule also remained. She was instructed to discontinue Cosopt and slowly taper Pred-Forteʼ over a 30 day period. Also on this visit, 30-2 visual fields were full OU. Optic nerve head HRT revealed no secondary glaucomatous optic cupping or NFL defect OU. She was asked to return for a 1 month follow-up visit with refraction, keratometry, color, and stereopsis testing scheduled.

Figure 4.1 Follow-up #5 She returned for her 1 month visit as scheduled. She had stopped all topical medications. With a new refraction, best corrected VA was unchanged at 20/30 OU without PH improvement. Color plates and stereopsis was normal. Autokeratometry readings did not reveal associated secondary atypical corneal cylinder or distortion remaining in the right eye. Without evidence of other visually significant ophthalmopathy, the slightly reduced VA was attributed to her mild lens changes in each eye. The slight ovoid pupil and trace anterior lens capsule pigmentary debris were the only indicators of previous activity and were not considered visually significant. OD IOP was stable at 10mm Hg. OS remained unremarkable. There was no evidence of recurrent or chronic inflammatory disease in either eye. She was advised that should her vision decrease due to progressive cataractous lens changes or if her current best corrected visual acuity was not sufficient, she may consider cataract surgery provided there was no evidence of active inflammatory ocular disease or systemic contraindications. Laboratory Subsequent laboratory results proved to be negative without suspicion of contributing infectious or inflammatory systemic disease. Chest XR was also negative without sign of prior or chronic pulmonary disease. Discussion As with this case, the etiology of Posner-Schlossman syndrome (PSS) remains difficult to target and is rarely uncovered. Worldwide statistics reveal the rarity of

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the condition although there is a prevalence of 1.9 per 100,000 within the Finnish population.1 The initial diagnosis normally falls between 20 – 50 years of age; however, as exemplified by the preceding report, cases have been described over age 60.6 A suspected case of PSS in a child has also been reported in the literature.1 Unilateral involvement is found in the majority of cases although it is possible to have alternating or simultaneous bilateral involvement.1,3,5,7,8,9 PSS tends to be recurrent with or without mild episodic symptoms continuing for hours, days, or weeks.1,3,5,9 Therefore, chronic subclinical disease may be unbeknownst to the individual. Characteristically there is an acute dramatic rise in intraocular pressure out of proportion to the uveal inflammation.1,5,9 The IOP rise can be present several days before discernable biomicroscopic evidence.1 It is not uncommon to find peak IOP levels reaching 40mm Hg – 60mm Hg during the active phase.1 IOP levels may also vary rapidly and widely between exacerbations.1 If the diagnosis is not made and treatment is not instituted with careful monitoring, it is only reasonable to conclude that individuals susceptible to recurrences are most likely to develop permanent pressure related glaucomatous optic neuropathy and visual field loss. It is theorized that recurrent inflammatory pathophysiologic changes occur within the trabecular meshwork leading to a corresponding decrease in aqueous outflow.1,5 Of course, restricted outflow contributes to an increase in intraocular pressure. Electroretinogram studies during IOP peaks have shown a diminished S-cone b-wave.1 Studies have also confirmed associated transient retinal blood flow alterations as well as transient optic nerve disruption within the acute phase of PSS.1 Additionally, there have been isolated cases of secondary non-arteritic anterior ischemic optic neuropathy (NAION) presented in the literature.7,8 Possible contributors to trabeculitis or trabecular inflammatory disease are abnormal micro-vascular metabolism, autonomic nervous system deficits, intraocular disease such as CMV or herpes simplex, and corneal disorders such as herpetic keratitis.1,5 Systemic inflammatory or auto-immune disease may co-exist with examples including but not limited to rheumatoid arthritis, ankylosing spondylitis, sarcoidosis, lupus, gastro-intestinal disease, immunologic factors including HLA-Bw54, and allergy.1,5 As described in the case, diagnostic laboratory and radiologic studies are imperative. With evidence of systemic disease, the formation of a long-term treatment plan can be established within the appropriate specialties. It is of interest to note that upon histological examination, atypical non-granulomatous keratic precipitates are characteristic of PSS. Corneal endothelial KPʼs tend to aggregate together as clusters with the formation of pseudopod

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extensions between them.1 This is in contrast to scattered or mutton-fat focal KPʼs present in other uveitic disorders.2 With recurrent or longstanding uveitic disease, a secondary iris vasculopathy consisting of tortuous vessels and leakage upon fluorescein angiography may develop.1 Consequently, secondary iris ischemia and atrophy may be apparent in longstanding cases.1,5 Ocular inflammatory disease, particularly uveitic disease, has been known to be mediated by prostaglandin involvement.1,5 Specifically, prostaglandin E has been found in elevated concentrations within the aqueous during the acute phase of uveitic crises with increased IOP.1,5 Prostaglandin E levels have been shown to return to normal levels between episodes of activity.1,5 Understanding the role of prostaglandin mediated uveitic glaucoma including Posner-Schlossman syndrome, the therapeutic approach can be better understood. The disease process must be strategically controlled by first considering the reason for the ocular hypertensive event and providing proper countering medical treatment. Therefore, as reported in the case study, steroidal anti-inflammatory and ocular hypotensive agents are utilized in conjunction with each other. Mydriatic agents are also utilized to mechanically stabilize the iris. In the event of decreasing uveal inflammation but with persistent ocular hypertension, the possibility of the patient being a “steroid responder” must be considered. In this situation, topical NSAID treatment will become the superior choice and can also be effective therapy without the potential for secondary ocular hypertension. Considering that the mechanism of NSAID agents involve the inhibition of prostaglandin synthesis, this is another powerful treatment option. Miotics such as Pilocarpine are contraindicated due to their constrictive effect on the iris potentially exacerbating the uveitis. Ocular hypotensive prostaglandin agonist therapy is also contraindicated due to the possible enhancement of the inflammatory cascade. Rarely is surgical intervention indicated but can be utilized in atypical unresponsive ocular hypertensive situations.1 Threshold visual field testing, optic disc photos, and optic disc analysis by HRT, GDx, or OCT must also be part of the treatment plan. Depending on the absence or presence of associated glaucomatous optic cupping, NFL defect, and/or visual field defect, the aggressiveness of treatment and corresponding recall schedule can be evaluated and instituted properly. In the event of associated systemic disease, proper communications and referrals to the appropriate specialties is of priority. Treatment of underlying

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causative systemic conditions can ultimately lead to better control of secondary ocular inflammation and IOP. Conclusion Understanding and differentiating uveitic glaucoma, inflammatory glaucoma, glaucomatocyclitic crisis, and Posner-Schlossman syndrome in the literature, we are consequently provided with opportunity for thought provoking analyses of these rare and potentially blinding conditions of unknown or conflicting etiologies. This case calls upon our understanding at multiple levels. Knowledge of the inflammatory process as it relates to uveitic disease, the pathophysiology of ocular hypertension and its effect on the integrity of the optic nerve, and the associated patterns of visual field loss. Knowledge of the pharmacodynamics of medical treatment to reduce ocular inflammation and secondary ocular hypertension. Finally, knowledge of possible associated systemic disease with the proper recommendation and interpretation of laboratory and radiologic testing. Unlike the idiopathic PSS case described, the possible association with systemic disease allows us as clinicians to be in a unique and exciting position. Many ocular conditions put us on the front lines to probe and initially discover treatable co-existing disorders. By understanding and utilizing laboratory and radiologic testing, very often the initial systemic diagnoses can be first made in a primary or medical eyecare setting. This allows for prompt, efficient, cost-effective, and appropriate referrals. Not only are we in a position to save vision, we are sometimes in a position to save a life. Contributing in this way to our patientsʼ overall health care experience can be extremely rewarding and is part of our responsibilities as primary and medical eyecare providers. Bibliography

1. Oakman J. Posner-Schlossman syndrome, eMedicine. Retrieved March 31, 2007, from www.emedicine.com/oph/topic137.htm.

2. Herndon, Jr L. Uveitic Glaucoma, eMedicine. Retrieved March 31, 2007, from www.emedicine.com/OPH/topic145.htm.

3. Scott KS, Wade NK. Posner-Schlossman syndrome, American Uveitis Society. Retrieved March 31, 2007, from www.uveitissociety.org/pages/diseases/pss.pdf.

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4. Teoh SB, Thean L, Koay E: Cytomegalovirus in aetiology of Posner-Schlossman syndrome: evidence from quantitative polymerase chain reaction. Eye 2005 Dec; 19(12): 1338-40.

5. Ralph J Green DipAppSc(Optom) (2007) Posner-Schlossman syndrome (glaucomatocyclitic crisis) Clinical and Experimental Optometry 90 (1), 53–56.

6. Marja-Liisa Vuori (2003) Complications of Neodymium: YAG laser goniopuncture after deep sclerectomy Acta Ophthalmologica Scandinavica 81 (6), 573–576.

7. Kim R, Van Stavern G, Juzych M: Nonarteritic anterior ischemic optic neuropathy associated with acute glaucoma secondary to Posner-Schlossman syndrome. Arch Ophthalmol 2003 Jan; 121(1): 127-8.

8. Irak I, Katz BJ, Zabriskie NA, Zimmerman PL. Posner-Schlossman syndrome and nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2003 Dec; 23(4):264-7.

9. Branch SL. Posner-Schlossman syndrome and medical certification. Aviat Space Environ Med 2006; 77:1092-1093.