Strabismus in adults with uveal melanoma followingepiscleral plaque brachytherapyEmma Dawson, DBO,a Mandeep S. Sagoo, MB, PhD, MRCOphth,b

Jodhbir S. Mehta, FRCS, FRCOphth,a Richard Comer, MD, FRCOphth,a

John Hungerford, FRCS, FRCOphth,b and John Lee, DM, FRCS, FRCP, FRCOphtha

PURPOSE To ascertain the incidence of persistent strabismus in patients treated with plaquebrachytherapy and its subsequent treatment.

METHODS A single center retrospective case note review of adult patients with persistent diplopia orstrabismus following plaque brachytherapy for all types of intraocular tumors between1996 and 2004.

RESULTS A total of 929 consecutive adults underwent plaque brachytherapy during the study periodat a single center. Sixteen patients (1.7%) with treated uveal melanoma developed per-sistent diplopia or strabismus. In 11 patients (69%) the timing of onset was in the firstyear, in 2 (13%) in the second year, and one each (6% each) in years 5, 7, and 8. Twopatients (13%) did not require any intervention. Fourteen patients (88%) required treat-ment: 7 (50%) were treated with prisms only, 3 (21%) underwent botulinum toxin(BTXA) injections, and 4 (29%) were treated with extraocular muscle surgery (3 requiredone operation and one required 2 procedures).

CONCLUSIONS The incidence of ocular motility disorders following plaque brachytherapy in our cohortwas 1.7% over 8 years and we include this in the consent process for conservativetreatment of intraocular tumors. Options for treatment for persistent diplopia or strabis-mus include prisms, botulinum toxin injection, or surgery. ( J AAPOS 2007;11:584–588)

T he aim of therapy for malignant ocular tumors isto offer the best prognosis for patient survival, forglobe retention, and for sight. Plaque brachyther-

apy is a well-recognized treatment for uveal malignantmelanoma and has been used in other intraocular tu-mors.1-5 It has the advantage of preserving the globe withrelatively low radiation exposure to healthy adjacent tis-sues but may result in significant ocular complications.6-8

Ocular brachytherapy often requires placing the plaqueunder an extraocular muscle or disinserting an extraocularmuscle partially or fully to enable accurate positioning.Patients may present with ocular motility disturbance aftertreatment for uveal malignant melanoma with plaquebrachytherapy,9 often from mechanical limitations of oc-ular movements resulting in symptomatic diplopia.10 Inaddition, patients with poor vision post treatment, as aresult of radiation retinopathy or optic neuropathy, may

aAuthor affiliations: aStrabismus Service and bOcular Oncology Service, Moorfields EyeHospital, London, United Kingdom

Presented at the 32nd Annual Meeting of the American Association for PediatricOphthalmology and Strabismus, Keystone, Colorado, March 15-19, 2006, and at theInternational Congress of Ocular Oncology, Whistler, Canada, 2005.

Submitted September 20, 2006.Revision accepted April 16, 2007.Published online June 26, 2007.Reprint requests: John Lee, DM, FRCS, FRCP, FRCOphth, Moorfields Eye Hospital,

City Road, London EC1V 2PD United Kingdom (email: john.lee@moorfields.nhs.uk).Copyright © 2007 by the American Association for Pediatric Ophthalmology and

Strabismus.

1091-8531/2007/$35.00 � 0doi:10.1016/j.jaapos.2007.04.005

584

also develop sensory deviations. The aim of this study wasto ascertain the incidence of strabismus following plaquebrachytherapy and to explore the management options forstrabismus following this treatment in a large series ofpatients.

Patients and MethodsWe reviewed the case notes of adult patients identified from acomputerized database as having developed persistent diplopia orstrabismus following plaque brachytherapy for intraocular tu-mors between October 1996 and October 2004. Plaques wereapplied to the episclera of the affected eye by one senior author( JLH) while the patient was under either general anesthesia orlocal anesthesia with intravenous sedation. The eye containingthe tumor was identified by indirect ophthalmoscopy preopera-tively. The conjunctiva and Tenon’s capsule were dissectedand the borders of the tumor were identified either by indirectophthalmoscopy, by transillumination, or by a combination ofboth techniques. A dummy plaque was used to preplace theepiscleral sutures and check correct alignment of the plaque tothe tumor. The plaque, of either ruthenium (Ru-106) or iodine(I-125) radionuclides, was sutured to the sclera, using 5-0 Ethi-bond suture (Ethicon, Edinburgh, UK). If the location of thetumor was directly beneath an extraocular muscle, the plaquecould be placed under the belly of the muscle. If the tumor wasdirectly below a rectus muscle insertion, the muscle was tempo-rarily disinserted, the plaque was sutured to the episclera incorrect position, and the muscle was reinserted over the plaque

with preplaced sutures (6-0 Vicryl; Ethicon) inserted into the

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sclera on either side of the plaque. The advantage of this tech-nique was to allow removal of the plaque without disturbing theposition of the muscle. If the tumor was partly under anoblique extraocular muscle, partial or total disinsertion wasachieved by severing a portion or all of the muscle at theinsertion. The plaque was removed at a time specified fromradiation dosimetry calculations. Following surgery, patientsreceived topical antibiotic, steroid, and atropine drops for 4weeks. Those that had persistent ocular motility disturbancefor greater than 6 months were referred for further evaluationto the Strabismus Service.

All patients had a detailed ophthalmic history with notes ofprevious ocular problems, including a past history of strabismusand diplopia, and underwent a full ophthalmic examination in-cluding Snellen visual acuity, anterior and posterior segmentexaminations, applanation tonometry, transillumination, and oc-ular ultrasonography pre- and postoperatively. Detailed ocularmotility examination was not performed prior to plaque therapy.Postoperative examination included cover test for near and dis-tance, ocular movements, prism cover test for near and distance,binocular vision assessment including convergence and fusion,and a Hess test. All ocular deviations, persisting after a minimumfollow-up period of 6 months, were managed by one seniorauthor ( JPL). The study was approved by our Research Gover-nance and Ethics Committee, which has the same remit as theIRB-HIPAA in the United States.

ResultsA total of 929 patients had plaque radiotherapy for in-traocular tumors at Moorfields Eye Hospital, London,during the study period. Persistent diplopia or strabismusdeveloped in 16 cases, giving an incidence of 1.7% in thiscohort. Table 1 charts the patient characteristics at pre-sentation in these 16 patients. The average age in thegroup was 60 years (mean, 58; range, 22-91 years) and 10patients (63%) were male. The left eye was the affected eyein 10 (63%) patients. In one case the treated eye wasamblyopic (6%) and no fellow eyes were amblyopic. Oc-ular copathology included cataract, primary open angleglaucoma, and previous strabismus surgery in one caseeach (6% each). The one case that had strabismus surgeryand the one case whose amblyopic eye contained the tu-mor were not the same patient.

Tumor characteristics and plaque radiotherapy param-eters are shown in Table 2. All 16 patients had malignantmelanoma of the uveal tract. The site of the tumor wasclassified as peripheral choroid in seven eyes (44%), pos-terior pole choroid in seven (44%), peripapillary choroidin one (6%), and iris melanoma in one (6%). The com-monest radionuclide isotope used was Ru-106 (13 eyes,81%) and three eyes received I-125 (19%). The size of theplaque was 20 mm in the majority (8 eyes, 62%), although15 mm was also used (5 eyes, 38%). The radiation dose tothe apex ranged between 80 and 120 gray, with a mediandose of 100 gray and mean of 93 gray. The median dura-

tion of plaque brachytherapy application was 76 hours

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(range, 36-140 hours). Final visual acuity of �20/200 wasobserved in five cases (33%).

Details of plaque brachytherapy surgery, visual out-come, subsequent ocular deviation, and its managementfor each individual case are listed in e-Supplement 1 (avail-able at www.jaapos.org). The radioactive plaque was posi-tioned under an extraocular muscle in 6 eyes (38%) andbetween muscles in 10 eyes (63%). In seven cases (44%)extraocular muscle removal was not required for plaque

Table 1. Strabismus after plaque brachytherapy: Patient characteristicsat presentation

Features Number (%) (N � 16)

Age ( years)Median (mean, range) 58 (60, 41-80)

SexMale 10 (63)Female 6 (37)

Laterality of affected eyeRight 6 (37)Left 10 (63)

Treated eye amblyopicNo 15 (94)Yes 1 (6)

Fellow eye amblyopicNo 16 (100)Yes 0 (0)

Ocular copathology*Cataract 1 (6)Primary open angle glaucoma 1 (6)Macular hole 1 (6)Previous squint surgery 1 (6)

*Some patients may have more than one condition.

Table 2. Strabismus after plaque brachytherapy: tumor, plaquetreatment, and outcome features

Features Number (%) (N � 16)

Tumor typeMalignant melanoma 16 (100)

Tumor locationPeripheral choroid 7 (44)Posterior pole choroid 7 (44)Peripapillary choroid 1 (6)Iris 1 (6)

RadionuclideIodine-125 3 (19)Ruthenium-106 13 (81)

Size of plaque (n � 13)15 mm 5 (38)20 mm 8 (62)

Plaque dose to apex (n � 15)80 gray 6 (40)100 gray 8 (53)120 gray 1 (7)

Plaque duration (h) (n � 12)Median (mean, range) 76 (81, 36-140)

Visual outcomeFinal visual acuity �20/200 5 (33)Loss of vision* 5 (33)

*Defined as loss of �6 Snellen lines or from any visual acuity to no light perception.

surgery. Total disinsertion of a muscle was necessary in

Volume 11 Number 6 / December 2007586 Dawson et al

five eyes (31%). These included the inferior oblique mus-cle (one eye) and superior oblique muscles (four eyes).Partial disinsertion became necessary for plaque surgery inthree eyes (19%); of these, the superior oblique muscle waspartially disinserted in two eyes and the lateral rectusmuscle was partially disinserted in one eye. In one case(6%), the inferior rectus muscle was disinserted and rein-serted to its natural origin at the time of plaque surgeryusing preplaced sutures over the plaque.

A sample of 215 case notes of the 929 patients under-going plaque brachytherapy during the study period wasavailable for further review to study the nature of musclesurgery during plaque application. This included muscledisinsertion, partial disinsertion, and disinsertion and re-insertion procedures. Of this subanalysis, 90 cases (42%)had muscle surgery and 125 cases (58%) had no musclesurgery during plaque application. In comparison, in the16 cases that subsequently developed persistent motilitydisturbance, nine cases (56%) had muscle surgery andseven cases (44%) had no muscle surgery during plaqueapplication. In the nine cases of motility disturbance thathad muscle surgery at the time of plaque surgery, manip-ulation of the superior oblique muscle and/or the inferioroblique muscles was the most common (seven cases, 78%)with only two cases (22%) of rectus muscle manipulation.In contrast, there were 81 patients that had muscle ma-nipulation for plaque surgery but did not develop a mo-tility disturbance; in this group the oblique muscles weremanipulated in 47 eyes (58%) and the rectus muscle wasmanipulated in 47 eyes (58%).

Of the 16 symptomatic patients, 5 (31%) had horizontalstrabismus; 4 (25%) had vertical, and in 7 (44%) a com-bination of horizontal and vertical ocular motility distur-bance was found. The time of onset of the motility dis-turbance is charted in Figure 1. Most presented in the firstyear after plaque brachytherapy (n � 11, 69%) with afurther two in the second year (13%). Late onset after 5years was noted in three cases (19%). The latter three eyeshad the most profound vision loss from radiation compli-cations (Cases 2, 3, and 15 in e-Supplement 1). Two wereno light perception (NLP) and one could see hand mo-tions only; these motility disturbances were secondarydeviations. None of these three eyes had extraocular mus-cles removed for plaque surgery. Among the other 13patients, 2 had a final visual acuity of counting fingers, butdid not lose vision by �6 Snellen lines (Cases 8 and 11,e-Supplement 1). In both cases, the superior oblique mus-cle was at least partially disinserted, and both developed ahorizontal and vertical ocular motility disturbance. In 11eyes the vision was retained in the range 20/17 to 20/120,although two cases from these experienced a reduction of�6 Snellen lines (Cases 13 and 16, e-Supplement 1).

Fourteen patients (88%) underwent intervention and 2(13%) patients declined treatment for their postbrachythe-rapy strabismus. Of the group requiring motility distur-bance management, seven patients (50%) were prescribed

prisms alone. Three patients (21%) were treated with

botulinum toxin, of whom two had lateral rectus muscleinjected and one the had the inferior rectus muscle in-jected. Of this group, one was symptom-free after a singleinjection; one patient required maintenance toxin at 5monthly intervals for a secondary exotropia due to a blindeye, and one had recurrence of choroidal melanoma re-quiring enucleation. Four patients (29%) underwent ex-traocular muscle surgery for the vertical component ofcombined horizontal and vertical motility disturbance. Allhad a positive traction test preoperatively. Of these four,two patients required only one surgical procedure, one hada Z-tenotomy of the superior oblique muscle, and theother had a combined resection and recession procedure,11

as described by Scott, on the inferior rectus muscle(a method of achieving the effect of a posterior fixationprocedure by combining resection and recession of a rec-tus muscle, while maintaining the ability to adjust primaryposition alignment with adjustable sutures). Both weresymptom free postoperatively. Of the remaining two pa-tients, one underwent repositioning of the superioroblique, which was found to be displaced anteriorly underthe superior rectus muscle insertion. The remaining pa-tient (Case 9, e-Supplement 1) underwent a tendon disin-sertion of the superior oblique muscle and 18 months laterrequired an inferior rectus muscle recession on adjustablesutures and was subsequently symptom-free.

DiscussionPlaque radiotherapy is an accepted treatment for intraoc-ular tumors. The advantages are retention of the eye, oftenwith good vision, and better appearance. However, pa-tients may still be at risk of complications such as phthisis,rubeosis, and motility disturbances. In this report wepresent our experience of one of those complications, theonset of persistent strabismus after plaque brachytherapyin a large series of patients from a single center.

Strabismus is known to occur following extraocular sur-

FIG 1. Onset of strabismus following plaque brachytherapy.

gica

l procedures including retinal detachment, glaucoma

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Volume 11 Number 6 / December 2007 Dawson et al 587

surgery, and anesthesia for cataract surgery.12-14 The stra-bismus in these patients may be caused by a combinationof conjunctival scarring, fat adherence syndrome, anddamage to the rectus muscles, resulting in a mechanicalstrabismus. In glaucoma surgery, the use of drainage de-vices may also result in restrictive strabismus.15 Diplopiafollowing retinal detachment surgery can be due to ante-rior displacement of the superior oblique tendon by theexplant16 (also described by Marshall Parks).17 This is asimilar surgical finding to one of our four patients thatunderwent surgery for ocular motility disturbance.

Relatively little attention has been given to the effect ofepiscleral plaque brachytherapy on ocular muscle balance.Langmann and associates9 reported transient motilityproblems after Ru-106 plaque brachytherapy with an in-cidence of 5 of 30 cases (16.7%). In that series full recoveryoccurred in all cases by 6 months without surgical inter-vention. Another series reported 12 of 20 patients (60%)developing strabismus after I-125 plaque treatment.10 Ofthese, only two required intervention. The incidence ofocular motility disturbance persisting longer than 6months in our single center series of 929 patients treatedwith plaque brachytherapy was 1.7% (n � 16) over 8 years.It is entirely possible that more patients developed tran-sient strabismus following plaque surgery, which settledspontaneously within 6 months. The patients reportedherein are only those whose motility disturbance did notresolve within the specified time period.

The choice of radiation modality for intraocular tumorsremains a topic of discussion.18,19 In a prospective ran-domized trial of I-125 plaque brachytherapy versus heliumion irradiation, the incidence of secondary strabismus was5% in plaque-treated patients compared with less than 2%in the helium ion group.18 Our study comprised onlypatients treated with plaque radiotherapy, although bothI-125- and Ru-106-treated patients were included fromthe 8-year period. During this time, we have reduced thenumber of I-125 treatments in favor of Ru-106, but it isdifficult to explain the disparity between the quoted 5%18

and our results on the basis of radioisotope alone. In aprevious report there was no statistical difference in visionloss between I-125 and Ru-10619 so we do not anticipatemore sensory strabismus with the use of one isotopeover another. In the present study, 3 cases of 16 wereclassified as having strabismus secondary to vision lossand all of these had a late onset of strabismus 5, 7, and8 years after plaque treatment, once profound visionloss had occurred.

Most cases presented within the first 2 years after plaquesurgery with relatively good vision and were of mechanicaletiology with restriction from scarring and fibrosis. Dur-ing plaque surgery, 56% of eyes had at least partial disin-sertion of an extraocular muscle, most commonly the ob-liques due to their posterior insertions. The pattern ofhorizontal or vertical motility disturbance could not al-ways be predicted by the muscle manipulation at plaque

surgery, due to the secondary and tertiary actions of the

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muscles and possible wider inflammation than just theimmediate radiation field of the plaque. Comparison witha subgroup of patients who did not develop motility prob-lems but had muscle surgery during plaque applicationshowed a smaller proportion of oblique muscle manipula-tions than those that subsequently developed motilityproblems.

Those patients requiring intervention were treatedwith prisms, botulinum toxin, or extraocular muscle sur-gery, with one case requiring two separate surgical proce-dures. All 14 patients had a favorable outcome defined assymptom-free for near and distance and only one stillrequires intervention for motility disturbance. This pa-tient remains asymptomatic on maintenance botulinumtoxin injections. One patient from this group had suc-cessful strabismus management, but recurrence of thechoroidal melanoma necessitated enucleation.

We conclude that the incidence of strabismus followingplaque brachytherapy was 1.7% over an 8-year period. Werecommend that patients should be informed of this po-tential risk during the consent process before plaquebrachytherapy and symptom enquiry after plaque treat-ment should include diplopia.

References

1. Hungerford JL. Current trends in the treatment of ocular melanomaby radiotherapy. Clin Exp Ophthalmol 2003;31:8-13.

2. Finger PT. Radiation therapy for choroidal melanoma. Surv Oph-thalmol 1997;42:215-32.

3. Shields CL, Shields JA, Gunduz K, Freire JE, Mercado G. Radiationtherapy for uveal malignant melanoma. Ophthalmic Surg Lasers1998;29:397-409.

4. Madreperla SA, Hungerford JL, Plowman PN, Laganowski HC,Gregory PT. Choroidal hemangiomas: Visual and anatomic resultsof treatment by photocoagulation or radiation therapy. Ophthalmol-ogy 1997;104:1773-8; discussion 9.

5. Shields CL, Shields JA, Cater J, Othmane I, Singh AD, Micaily B.Plaque radiotherapy for retinoblastoma: Long-term tumor controland treatment complications in 208 tumors. Ophthalmology 2001;108:2116-21.

6. Summanen P, Immonen I, Kivela T, Tommila P, Heikkonen J,Tarkkanen A. Radiation related complications after rutheniumplaque radiotherapy of uveal melanoma. Br J Ophthalmol 1996;80:732-9.

7. Shields CL, Shields JA, Cater J, Gunduz K, Miyamoto C, Micaily B,et al. Plaque radiotherapy for uveal melanoma: Long-term visualoutcome in 1106 consecutive patients. Arch Ophthalmol 2000;118:1219-28.

8. Melia BM, Abramson DH, Albert DM, Boldt HC, Earle JD, HansonWF, et al. Collaborative ocular melanoma study (COMS) random-ized trial of I-125 brachytherapy for medium choroidal melanoma. I.Visual acuity after 3 years COMS report no. 16. Ophthalmology2001;108:348-66.

9. Langmann A, Langmann G, Unlucerci C, Haller E. [Motility disor-ders in brachytherapy of choroid melanomas with Ru106 applica-tors]. Ophthalmologe 1995;92:76-8.

10. Sener EC, Kiratli H, Gedik S, Sanac AS. Ocular motility distur-bances after episcleral plaque brachytherapy for uveal melanoma.

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11. Scott AB. Posterior fixation: Adjustable and without posterior su-tures. VIIth Congress International Strabismological Association,1974;399-402.

12. Munoz M, Rosenbaum AL. Long-term strabismus complicationsfollowing retinal detachment surgery. J Pediatr Ophthalmol Strabis-mus 1987;24:309-14.

13. Munoz M, Parrish RK 2nd. Strabismus following implantation ofBaerveldt drainage devices. Arch Ophthalmol 1993;111:1096-9.

14. Kushner BJ. Case report. Ocular muscle fibrosis following cataractextraction. Arch Ophthalmol 1988;106:18-9.

15. Christmann LM, Wilson ME. Motility disturbances after Molteno

implants. J Pediatr Ophthalmol Strabismus 1992;29:44-8.

16. Metz HS, Norris A. Cyclotorsional diplopia following retinaldetachment surgery. J Pediatr Ophthalmol Strabismus 1987;24:287-90.

17. Parks MM. Discussion of: Wright KW. The fat adherence syndromeand strabismus after retinal detachment surgery. Ophthalmology1986;93:411-5.

18. Char DH, Castro JR, Quivey JM, Phillips TL, Irvine AR, Stone RD,et al. Uveal melanoma radiation. 125I brachytherapy versus heliumion irradiation. Ophthalmology 1989;96:1708-15.

19. Wilson MW, Hungerford JL. Comparison of episcleral plaque andproton beam radiation therapy for the treatment of choroidal mela-

noma. Ophthalmology 1999;106:1579-87.

An Eye on the Arts – The Arts on the Eye

Don’t Whine

Today I saw a lovely girl with golden hair,envied her and wished I were so fair.When she rose to go, she hobbled down the aisle.She had one leg, wore a crutch and a smile.Oh god forgive me when I whineI have two legs, the world is mine.

Then I stopped to buy some sweets.The lad who sold them had such charm.I talked with him—my being late was no harm.As I left he said to me, “You’ve been so kind.You see,” he said, “I am blind.”Oh god forgive me when I whineI have two eyes, the world is mine.

Later, I saw a child with eyes of blue.Watching others play, not knowing what to do.“Why don’t you join the others, dear.”He stared ahead, he could not hear.Oh god forgive me when I whine. . . .

author unknown—Ann-Marie MacDonald (from Fall on Your Knees, Vintage Canada)

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