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LASER PHOTOCOAGULATION AS MANAGEMENT OF RETINOBLASTOMA

AbstractIntroductionThe management of retinoblastoma can be complex, and it is impossible to establish firm rules regarding treatment. There are several options available for the treatment of retinoblastoma, and the method selected should depend on the size and extent of the tumor(s), whether there is unilateral or bilateral involvement, and the patient’s systemic status. Lasers have played a central role in the treatment of retinoblastomas since the very start of the laser era.ObjectivesTo review two cases of retinoblastoma treated by photocoagulation therapyCaseAn one-month old baby boy came with his parent with chief complain white freckle in his right eye. From evaluation under anesthesi (EUA), two intraocular masses on inferolateral quadrant were found, size of two masses were 0,5 DD (disc diameter) and 1 DD. He was diagnosed as intraocular masses ec suspect retinoblastoma grade A OD. Photocoagulation with diode laser (810 nm) was performed. One month after laser therapy, the size of intraocular masses was same as before. A three-month old baby girl came with chief complain white freckle on herleft eye since two weeks ago. Patient was diagnosed as retinoblastoma grade B OD et grade D OS. He had undergone chemotherapy, laser photocoagulation for her right eye, and cryo therapy for her left eye. Five years later intraocular mass in herleft eye progressed, she was diagnosed as retinoblastoma grade B OD et grade D-E OS and suggested to enucleation OS. Enucleation of left eye was performed. ConclusionPhotocoagulation can be used as local primary therapy and consolidation treatment following primary systemic chemotherapy to eliminate the tumor cells that were resistant to or were not inactivated by primary therapy. Photocoagulation alone, as local primary therapy, appears to be an appropriate method of management in cases where the tumor is small in diameter.

I. Introduction

Retinoblastoma is the most common malignant ocular tumor of childhood,

with incidence of 1:14.000-1:20.000 live births. This neuroblastic tumor is

typically diagnosed during the first year of life in familial and bilateral cases and

between ages 1 and 3 in sporadic unilateral cases. The most common initial sign is

leukokoria (white pupil) described as a glow, glint, or cat’s eye appearance. Other

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presentations include vitreous hemorrhage, hyphema, ocular or periocular

inflammation, glaucoma, proptosis, and pseudohypopion.1,2

The first goal of retinoblastoma must be preservation of life, then

preservation of eye, and finally preservation of vision. The management of

intraocular retinoblastoma currently incorporates a combination of different

treatment modalitas, including enucleation, chemotherapy, photocoagulation,

cryotherapy, external beam radiation therapy, and plaque brachiotherapy.

Photocoagulation therapy using xenon arc and argon laser (532 nm) or diode laser

(810 nm) have been used to treat retinoblastoma smaller than 3 mm in apical

height with asal dimensional less than 10 mm. Over the years, the result were

comparable between the various types of laser, and a tumor control rate of

approximately 80% was achieved. The currently popular diode laser, used with an

adjustable, indirect opthalmoscope, is far easier to use than the xenon arc

photocoagulator, and moreover has a more favorable absorption range within the

eye than the argon laser.1,3

This study reports a case series of retinoblastoma which treated with

photocoagulation laser therapy in vitreoretinal department of Cicendo Eye

Hospital.

I. Case Report

II.1 Case I

An one-month old baby boy, baby K, came with his parental to vitreoretina

department of Cicendo Eye Hospital. His parents complain about white freckle in

their son’s right eye. Patient was born in the hospital normally through vaginal

birth on 37 weeks of gestation, his birth weight was 3100 grams. There was no

history of illness during pregnancy. He was born from a G1P1A0 mother. On one

month old, his weight was 5330 grams.

From ophthalmological examination, visual acuity was blink reflex for both

eyes. Anterior segment examination was within normal limit. Funduscopy

examination of right eye revealed clear media, round papil, clear border, c/d ratio

0,3-0,4, a/v ratio 2:3, flat retina, fovea reflex (+), two intraocular masses on

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inferolateral quadrant, their size were 0,5 DD (disc diameter) and 1 DD.

Funduscopy examination of left eye was within normal limit, optic disc drusen

(+).

This baby boy was diagnosed multiple intraocular masses e.c susp

retinoblastoma grade A OD + optic disc drusen OS. This patient was consulted to

pediatric ophthalmology unit to undergo retcam examination and his condition

was informed to his parent. The following is his first retcam photograph.

Figure 2.1 Retcam photograph of both eyes before laser treatmentSource : Cicendo Eye Hospital

He was suggested to undergo laser treatment for masses on right eye. One

month later, he undergone laser therapy surrounding the masses in general

anesthesia with infrared (810 nm), duration was 0,20 second, power was 300 mW,

amount of laser spot was 313.

One month after laser treatment, he and his parents came to follow up. On

second month old, his body weight was 4000 gram. Anterior segment examination

was within normal limits for both eyes. Funduscopy examination of right eye

revealed two intraocular lesions on inferolateral quadrant, their size were still 0,5

DD (disc diameter) and 1 DD, scar laser surrounding lesions, pre-lesions

hemorrhage (+), the others were same as before. Funduscopy examination of left

eye was within normal limit, optic disc drusen (+), NV (-), slight turtoisity. Patient

undergone retcam examination and his parent was adviced to come next month.

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Figure 2.2 Retcam photograph of both eyes one month after laser treatmentSource : Cicendo Eye Hospital

II.2 Case II

A-three month old baby girl, baby A, came on January 2010 with her

parents to Cicendo Eye Hospital with chief complain white freckle on her left eye

since two weeks ago. She was born through caesarian delivery with birth weight

2715 grams from a G2P2A0 mother on 37 weeks of gestation. Her sister is 2,5

year folder than hers. No history of ilness during pregnancy. No history of ocular

tumor in her family. Ophthalmological examination revealed blink reflexes for

both eyes. Anterior segment examination showed cat’s eye (+) on the left eye,

others were within normal limit. Patient underwent first ultrasonography (USG)

examination and was diagnosed as intraocular mass e.c retinoblastoma ODS

(OS>OD). She got chemotherapy from hemato-oncologist pediatrician. CT scan

examination revealed exophytic mass e.c suspect retinoblastoma OS, 18x12x17

mm. No expansion to retrobulbar space or optic nerve or intracranial. Suspect

small retinoblastoma OD juxta optic disc, confined to oculi, measuring 3 mm.

Three months later on April 2010 from USG, there was regression of

intraocular mass of left eye, vitreous cavity was clearer while intraocular mass on

right eye was as small as before. Second CT scan revealed that the mass in left eye

had shrunk, there was no soft tissue mass, only calsified nodule 10x4x13 mm, no

expansion to optic nerve or intracranial. There was no mass in right eye ball.

Four months later on August 2010 USG of right eye showed an echogenic

mass, 4,46 mm x 0,81 mm, moderate to high reflectivity, no mobility and a mass

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13,5 mm x 2,91 mm, calcification (+), shadowing (+) on left eye. Baby A was

diagnosed as retinoblastoma grade B ODS. Three months later, she underwent

evaluation under anestesi (EUA) and photocoagulation therapy. From indirect

funduscopy on right eye there were retina flat, tumor with diameter was a half of

disc diameter, calsification (+), while there was mass about half of posterior eye

ball about 2 DD, solid, vitreous seeding (+). The patient was diagnosed as

retinoblastoma grade B OD et grade D OS. The tumor was responsive to

chemotherapy. Patient underwent photocoagulation OD using LIO (laser indirect

ophthalmoscopy) diode 810 nm during EUA, then continued her chemotherapy.

Figure 2.3 showed USG examination of left eye

Source : Cicendo Eye Hospital

Seven months later (on June 2011), from indirect funduscopy on right eye there

were retina flat, tumor with diameter was a half of disc diameter, calsification (+), while

there was mass about half of posterior eye ball about 2 DD, solid, vitreous seeding (-).

Patient was diagnosed as retinoblastoma grade B ODS (resolving). CT scan revealed no

mass on right eye and a solid mass with calcified nodule size 4 x 10 x 12 mm, no

extension to optic nerve or intracranial on left eye.

Seven months later (on January 2012) she underwent EUA. Indirect funduscopy

examination revealed a mass with size 1,5 DD on superior portion, vitreous seeding (-),

laser scar (+) and a mass with size 4 DD on inferior, laser scar (+), with cherry with

appearane in the center of mass on right eye and chery white mass 8 DD, calcified,

vitreous seeding (+) on inferiortemporal quadrant and cyctic mass, more than 4 DD. She

was diagnosed as retinoblastoma gr B-C OD et gr D-E OS and suggested to enucleation

OS + photocoagulation OD. Two months later right eye was treated by cryotherapy.

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On July 2012 EUA revealed on right eye tumor mass, flat retina, laser scar, no

vitreous seeding and on left eye increased size of tumor mass, neovascularization,

increased vitreous seeding. She was suggested to continue the chemotherapy and focal

radiotherapy after consulted to pediatrician, and observation of left eye.

On November 2012 EUA revealed on right eye white tumor mass on superior and

inferior, 7-8 DD, clear border, flat with vascularization on the mass, suggestive

retinoblastoma grade B. On left eye there was retinal detached, vitreous seeding, tumor

mass on lateral portion with clear border, vascularization, elevated but not clear border,

diameter 20 DD, suggestive retinoblastoma grade D-E. Patient was suggested to

enucleation of left eye. Visual acuity was 0,5 with cardiff 50 cm. This patient had

undergone 50 times chemotherapy in Hasan Sadikin Hospital. Her liquor cerebrospinal

fluid (LCS) examination result revealed there was no blast cell. On March 2015, her

visual acuity of right eye 0,8 with cardiff 1 meter and no light perception (NLP) for left

eye, then enucleation was perfomed. Pathology anatomy examination result showed that

retinoblastoma of left eye has invaded choroid and optic nerve.

Figure 2.2 Retcam photograph of left eye on July 2012 and November 2012

Source : Cicendo Eye Hospital

II. Discussion

Any white or yellow lesion in the posterior segment of the eye in a child

under 5 years of age should raise the possibility of retinoblastoma. This disease is

highly curable in its early stages but can be fatal if the diagnosis is missed or

delayed. In a large majority of children with this disease, including this case, a

parent or family member first notes the presence of a white pupillary reflection or

reflex (leukocoria). A posterior pole tumor as small as 3 to 5 mm in diameter has

the capacity to create leukocoria. The term that parents use for the leukocoria

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observation is rarely the textbook-cited “cat’s eye.” Usually it is a “g” word, such

as “gleam, glow, glare, or glint”.4

The differential diagnosis of leukocoria are retinoblastoma, persistent

hyperplastic primary vitreous (PHPV), cataract, retinopathy of prematurity,

toxocariasis, coloboma of choroid, uveitis, coat’s disease, vitreous hemorrhage,

retinal dysplasia, tumors other than retinoblastoma, retinal detachment, corneal

opacity, and myelinated nerve fibers. Other presentations beside leukocoria

include vitreous hemorrhage, hyphema, ocular or periocular inflammation,

glaucoma, proptosis, and pseudohypopion.4

In case 1, this baby boy was diagnosed as suspect retinoblastoma grade A

OD + optic disc drusen OS because there was complain of leukocoria from his

parent and there were multiple white masses on retina from funduscopy

examination of right eye. According to International Retinoblastoma

Classification, this patient was suspected retinoblastoma grade A because group A

tumor are still small less than 3 mm in any diameter (base or height), no vitreous

seeding and located greater than 2 DD (3 mm) from the fovea and 1 DD (1,5 mm)

from the optic disc.

In case 2, this baby girl was diagnosed as suspect retinoblastoma grade B

OD et grade D OS because on her right eye the tumor was greater than 3 mm in

any diameter but there was not vitreous seeding or subretinal fluid and on the left

eye the tumor was large intraocular mass (endophytic disease) and diffuse vitreous

seeding.

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Table 3.1 International Retinoblastoma Classification: Grouping SystemSource : Rosa1

There are several options available for the treatment of retinoblastoma, and

the method selected should depend on the size and extent of the tumor(s), whether

there is unilateral or bilateral involvement, and the patient’s systemic status. In the

early 1990s several investigators from North America and Great Britain began

using systemic agents to treat intraocular retinoblastoma (CEV regimen,

comprising carboplatin, etoposide, and vincristine) that had been found to be

successful in the treatment of central nervous system neoplasms. Other indications

for chemotherapy in a patient with retinoblastoma include prophylaxis against

metastasis following enucleation in the presence of histopathologic high-risk

features, extraocular retinoblastoma with local and/or regional spread, metastatic

retinoblastoma with or without CNS involvement, and trilateral retinoblastoma.

Retinoblastoma in patients with bilateral disease or only moderately advanced

unilateral disease diagnosed today are treated with a protocol of systemic

chemotherapy given intravenously every 3 to 4 weeks followed by consolidation

(the use of a different dose of the same drug, a different drug, or different

treatment modality) with the focal surgical techniques of direct tumor

photocoagulation or cryotherapy or both.5

The two most common surgical procedures used as part of the treatment of

intraocular retinoblastoma are local therapy, either primary or for consolidation

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following systemic chemotherapy, and enucleation. Photocoagulation,

thermotherapy, chemothermotherapy, cryotherapy, brachytherapy, and external

beam radiotherapy could be considered local therapy.5,6

Tabel 3.2 Local treatment of retinoblastomaSource : Wright4

Photocoagulation is described by Meyer-Swickerath in 1949,

photocoagulation involves heating the tumor to temperatures above 65°C.

Photocoagulation can be used as primary treatment, consolidation treatment, and

for tumor recurrence. Group A eyes with small intraretinal lesions away from

critical structures are candidates for local primary therapy, such as direct laser

photocoagulation or cryotherapy. Loss of central vision from direct tumor

destruction or laser consolidation during treatment is minimized in group A by

restricting the tumor to locations greater then 2 DD (3 mm) from the fovea and 1

DD (1,5 mm) from the optic disc. The prognosis of group A is excellent.4,5,6

Photocoagulation treatment can use argon green laser (532 nm), diode

laser (810 nm), and transpupillary thermotherapy (TTT) using infrared diode laser

(810 nm) that couples large spot size (2–3 mm) and long burn duration (1 minute)

with low power settings. In these cases, patients were treated with diode laser

(810 nm).3,4,7 Patient of case 1 had photocoagulation as local primary therapy

according to grade A and still require follow up. Patient of case 2 had

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photocoagulation as consolidation therapy, following systemic chemotherapy for

retinoblastoma grade B OD et grade D OS.

The 810 nm diode laser is most effective when there is intact RPE beneath

the tumor. The indirect ophthalmoscope delivery system offers a spot size of 0.5

mm. This provides safety from the reduced likelihood of concentrated power

intensity in a small spot creating explosive disruption of the tumor and short

treatment time.3,4,5

Initial setting were 400–500 mW and 0,5–1,0 seconds. The power and

duration will vary for each patient because of the degree of pigmentation

underlying the lesion. Once the appropriate power level is set, the edge of the

tumor is treated with overlapping burns to establish its perimeter. Subsequently

the entire lesion should be treated with burns having the same overlap. In the

central, thicker portions of the tumor, the whitening reaction following treatment

may not be present. The treatment is repeated every 3–4 weeks immediately

before the next cycle of chemotherapy. A 2–4-week interval can be adopted if the

systemic chemotherapy has been completed.3,4,5

The most important effect is the direct heat mediated tumor cell kill. The

diode laser is most effective when intact RPE is present beneath the tumor to be

treated. If the RPE has been destroyed, most of the 810 nm wavelength energy

passes into the orbit without being absorbed by the retinoblastoma.3,4,5

When treating retinoblastomas with an indirect ophthalmoscope, children

should be anesthetized and the surgeon should first treat the area surrounding the

tumor and then the tumor itself, until the effect of coagulation is visible. Over-

treatment, for example, a power that is too high or a long exposure time, may

cause the spread of tumor cells within the vitreous cavity. This is a severe, eye

threatening complication. Others complications are retinal fibrosis and traction,

and retinal vascular occlusion. Tumors treated by laser coagulation should be

monitored closely since recurrent disease may develop even years after the initial

therapy.4,5

Study about retinoblastoma treated with photocoagulation only revealed

that photocoagulation appears to be an appropriate method of management in

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cases where the tumor is no greater than 3.0 mm in diameter and 2.0 mm in

thickness and is confined to the sensory retina, without seeding into the adjacent

vitreous. Photocoagulation alone is generally unsuccessful for tumors greater than

4.5 mm in diameter and greater than 2.5 mm in thickness and supplemental

treatment with other modalities was often necessary in such cases. Complete

regression occurred in 21 tumors (70%) and local recurrence in nine (30%).8

A case report about 18-month-old girl, a small (6.6x 4.3x 3.2-mm) discrete

retinoblastoma anterior to the superotemporal arcade in the right eye was treated

with transscleral photocoagulation using a diode laser (810 nm) and a fiberoptic

probe. The tumor regressed after photocoagulation, leaving a pigmented

chorioretinal scar. There was no regrowth of the tumor 12 months after

photocoagulation. The advantages of transscleral over transpupillary delivery

include the ability to treat tumor in the presence of media opacities, the larger

available spot size, and the avoidance of transmitting laser through the pupil,

which eliminates the risks of cataract and synechiae.9

III. Conclusion

Photocoagulation can be used as local primary therapy and consolidation

treatment following primary systemic chemotherapy to eliminate the tumor cells

that were resistant to or were not inactivated by primary therapy.

Photocoagulation alone, as local primary therapy, appears to be an appropriate

method of management in cases where the tumor is small in diameter. Complete

regression occurred in 70% cases and local recurrence 30% cases.