CLINICAL SCIENCES Palladium 103 (103Pd) Plaque for Circumscribed Choroidal Hemangioma With Retinal Detachment

Alexander Aizman, MD; Paul T. Finger, MD; Uri Shabto, MD; Andrzej Szechter, PhD; Anthony Berson, MD

Objective: To describe clinical experience with palla- ment. Three patients (60%) demonstrated improve- dium 103 (103Pd) ophthalmic plaque radiotherapy for cho- ment in visual acuity at the last follow-up, and in 1 roidal hemangioma. patient vision remained stable with resolution of meta- morphopsia. Twenty-four months after treatment, 1 Methods: One course of 103Pd ophthalmic plaque ra- patient whose visual acuity had recovered from 20/160 diotherapy was used in each of 5 patients with circum- to 20/32 had a loss of vision to 20/160 because of scribed choroidal hemangioma who had progressive loss radiation maculopathy. For all patients, a mean visual of vision due to subretinal exudation. A mean apex dose acuity improvement of 2 lines was documented (95% of 2900 cGy (2900 rad) was delivered. Functional tests confidence interval, 0.23-0.88). Mean follow-up was of outcome included best-corrected visual acuity. Ana- 18.6 months (range, 6-29 months). tomic results included changes in tumor height and sub- retinal fluid documented by , fluores- Conclusions: A single 103Pd plaque radiation treatment cein angiography, and ultrasonography. was effective in decreasing tumor height, eliminating sub- retinal fluid, and improving visual acuity in patients with Results: All patients had complete resolution of sub- symptomatic circumscribed choroidal hemangiomas. retinal fluid with reattachment of the retina. All tumors decreased in height (mean, 50%) after treat- Arch Ophthalmol. 2004;122:1652-1656

IRCUMSCRIBED CHOROI- rence of retinal detachments, multiple treat- dal hemangioma is a be- ments were required and the long-term nign vascular tumor that visual prognosis was poor.3-5 More re- typically appears as a cently, various researchers have reported subtle, amelanotic, red- successful treatments of symptomatic cir- orange mass in the posterior pole.1 Mild cumscribed choroidal hemangiomas by pho- C 6-8,15-20 yellow-white foci on the tumor surface may todynamic therapy (PDT). be present and represent fibrous metapla- Several researchers have also reported sia of the overlying retinal pigment epi- successful treatment of diffuse and circum- thelium.2 Visual acuity loss typically re- scribed choroidal hemangiomas with ra- sults from intraretinal edema, cystoid diation therapy.9,10,12,13 In 1996, Zogra- degeneration, and accumulation of sub- phos et al9 investigated cobalt 60 (60Co) retinal fluid. Massive exudation may lead and suggested that radio- to serous retinal detachment.3 therapy was the best therapeutic modality Various treatment modalities have been for the treatment of large hemangiomas, Author Affiliations: described for symptomatic choroidal hem- those that involve the macular area, and Departments of Ophthalmology, angiomas and have included penetrating hemangiomas associated with a bullous sec- New York Cancer Center diathermy, xenon photocoagulation, ar- ondary exudative retinal detachment. (Drs Aizman and Finger), New gon laser photocoagulation, microwave hy- Madreperla et al10 found that in patients York Eye and Ear Infirmary perthermia, external beam radiotherapy, with circumscribed choroidal hemangio- (Drs Shabto and Berson), and infrared diode laser thermotherapy, photo- mas treated with iodine I 125 (125I) or ru- New York University School of dynamic therapy, stereotactic radio- thenium 106 (106Ru) brachytherapy, 75% Medicine (Drs Aizman and therapy, and radioactive plaque therapy.3-14 had visual acuity of 20/40 or better at 1 year, Finger), and Department of Radiation , St Vincent’s Laser photocoagulation was previously and they noted resolution of subretinal fluid Comprehensive Cancer Center widely used to treat choroidal hemangio- in 100% of cases. Most recently, Kivela et 14 (Drs Szechter and Berson), New mas. The photocoagulation was scattered al reported their experience with stereo- York. over the tumor’s surface to reduce associ- tactic for circumscribed cho- Financial Disclosure: None. ated subretinal fluid.5 Because of recur- roidal hemangioma. They noted resolu-

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table 1. Hemangioma Characteristics and Palladium 103 Treatment

Pretreatment Tumor Dimensions,mm

Patient No./Sex/Eye Length Width Height Plaque Diameter, mm Apex Dose, cGy Treatment Duration, d 1/M/OD 8.0 9.0 3.6 14 2500 2 2/F/OD 6.6 5.5 4.0 12 4000 5 3/M/OS 9.0 9.0 2.8 14 2700 2 4/F/OS 7.0 9.0 3.4 12 3100 5 5/F/OD 8.0 8.0 2.5 12 2000 2

Conventional units: To convert apex dose to rad, multiply centigray by 1.

Table 2. Results of Palladium 103 Treatment

Tumor Height Visual Acuity

Patient No. Pretreatment, mm Final, mm Reduction, % Pretreatment Final Follow-up, mo 1 3.6 0.7 80 20/125 20/40 29 2 4.0 3.4 15 20/32 20/32 6 3 2.8 2.1 25 20/800 20/400 12 4 3.4 1.3 60 20/160 20/160 27 5 2.5 0.8 68 20/32 20/20 19 Mean 3.3 1.7 50 20/100 20/63 18.6

tion of subretinal fluid in all patients and suggested that and B-scan ultrasonography. A-scan ultrasonography was used stereotactic therapy be targeted to small and posteriorly to measure the height of the tumor and internal reflectivity. B- located circumscribed choroidal hemangiomas.14 scan ultrasonography was typically used to determine tumor In 1989, palladium 103 (103Pd) seeds became available location and shape and evidence of retinal detachments. Fluo- for brachytherapy.21 Comparative studies have shown that rescein angiography and were used to evalu- 103 ate and record patterns of tumor circulation, focal leakage, cys- whenequivalenttargetdoseswereprescribed,theuseof Pd toid macular edema, and radiation retinopathy. resulted in an increased dose within the targeted zone (tu- mor) and less radiation to most normal ocular tissues com- STATISTICAL ANALYSIS paredwith 125I.22 An11-yearstudyof 103Pdplaqueradiotherapy for choroidal melanoma found better visual function out- The clinical data were analyzed with regard to improvement in vi- 125 23 comes compared with the results from centers using I. sualacuityaftertreatment.TheSPSSsoftwarepackage,version11.01 Herein are reported what we believe to be the first vi- (SPSS Inc, Chicago, Ill), was used for data analysis. The modified sual and anatomic results of a series of patients with symp- Wald test was used to calculate 95% confidence interval. tomatic choroidal hemangiomas treated with 103Pd oph- thalmic plaque radiotherapy. PALLADIUM 103 OPHTHALMIC PLAQUE RADIOTHERAPY METHODS Palladium 103 seeds were available at strengths of up to 5 mCi PATIENT SELECTION (185 MBq) per seed (model 200; Theragenics Corp, Buford, Ga). The cylindrical titanium-encapsulated 103Pd seeds measured 0.8 A prospective, nonrandomized clinical study was conducted mm in diameter and 4.5 mm in length. Seeds were affixed into in 5 consecutive patients with previously untreated and symp- standard COMS (Collaborative Ocular Melanoma Study)– tomatic circumscribed choroidal hemangioma. The diagnosis type gold plaques (Trachsel Dental Studio Inc, Rochester, Minn) was made by clinical ophthalmoscopic, fluorescein angio- with a thin layer of medical-grade acrylic fixative. Because of graphic, and ultrasonographic features. Each patient partici- low energy of x-rays from 103Pd, the 0.5-mm-thick plaque pated in a detailed discussion of the risks and benefits of vari- blocked more than 99% of photons directed to the sides of and ous therapeutic modalities. All patients signed a statement of posterior to the plaque.22 Our methods of 103Pd plaque dosim- informed consent. Institutional review board approval was not etry have been described elsewhere.22,23 considered necessary because of the established use of radia- In this series, all patients received 1 radiation treatment. Eye tion therapy for choroidal hemangiomas. plaques were sewn to the episclera to cover the base of the in- traocular tumor, radiation was continuously delivered during DIAGNOSIS 2 to 5 days, and the plaques were removed. The tumor apex served as the radiation prescription point. Treatment time and Clinical history included the patient’s age, sex, and medical his- dose rate were calculated on the basis of the dimensions of the tory. Ophthalmic evaluations included a best-corrected visual tumors and followed COMS guidelines, whereby the apex dose acuity and pupillary, oculomotor, and slitlamp examinations. rate was kept between 50 and 125 cGy/h (50 and 125 rad/h). Goldmann tonometry was used to measure intraocular pres- Similarly, a treatment margin of 2 mm was included around sure. The basal dimensions of the tumors were determined by the edges of the tumor. The mean apex dose for the 5 patients ophthalmoscopy, , transillumination, who were treated with 103Pd was 2900 cGy (2900 rad) (Table 1).

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 A B

C D

E F

Figure. Pretreatment (A, C, and E) and posttreatment (B, D, and F) optic disc photographs, fluorescein angiograms, and ultrasound scans in a patient with circumscribed choroidal hemangioma treated with palladium 103 ophthalmic plaque radiotherapy. A, Pretreatment photograph showing the orange choroidal hemangioma extending beneath the fovea before brachytherapy. B, Posttreatment photograph demonstrating flattening of the tumor with residual retinal pigment epithelial mottling 29 months after treatment. C, Fluorescein angiogram before treatment showing a coarse intratumoral vascular pattern extending to the fovea. D, Pattern of residual transmission defects within the targeted zone. E, Pretreatment 10-MHz B-scan ultrasonogram demonstrating the highly reflective choroidal tumor and retinal detachment. F, Most recent ultrasound, obtained 25 months after treatment, showing a flattened choroidal hemangioma with complete resolution of the exudative retinal detachment. The plus sign represents the measuring cursor for the ultrasound image; the scale is in centimeters (larger intervals).

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table 3. Results of Photodynamic Therapy (PDT) for Choroidal Hemangioma

Mean Visual Acuity Mean Tumor Height, mm No. of Mean No. of Source Location of Tumor Patients PDT Treatments Pretreatment Final Pretreatment Final Schmidt-Erfurth et al,8 2002 Posterior pole 15 2.4 20/125 20/80 3.8 0.6 Robertson,15 2002 Posterior pole 3 1.7 20/100 20/30 3.0 0 Madreperla,6 2001 Posterior pole 3 1.0 20/50 20/25 2.4 0.4 Porrini et al,16 2003 Posterior pole 10 2.3 20/50 20/25 2.9 0.6 Landau et al,19 2002 Posterior pole 8 1.1 20/40 20/25 2.5 0.4 Sheidow and Harbour,20 2002 Posterior pole 1 2.0 20/400 20/50 3.8 0 Kjeka and Krohn,18 2002 Posterior pole 1 3.0 20/30 20/20 3.0 0 Jurklies et al,17 2003 Posterior pole 19 2.2 20/50 20/30 2.6 1.3 Mean 7.5 2.0 20/60 20/30 3.0 0.4

Table 4. Comparative Results of Plaque Radiation Therapy for Choroidal Hemangioma

Mean Mean Tumor Height Mean Visual Acuity No. of Minimum Follow-up, Source Patients Apex Dose, cGy Pretreatment, mm Final, mm Reduction,%Type of Radiation Pretreatment Final mo

Current study 5 2900 3.2 1.6 50 Palladium 103 plaque 20/100 20/63 18.6 Madreperla et al,10 9 5000 4.8 2.1 44 Iodine I 125 or 20/80 20/30 25.0 1997 ruthenium 106 plaque Ritland et al,12 12 2300 4.4 2.3 48 External beam 20/80 20/32 43.2 2001 Hannouche et al,13 11 3000 3.7 1.2 68 Proton beam 20/100 20/40 26.0 1997 Kivela et al,14 5 2000 2.9 2.1 28 Stereotactic 20/40 20/40 20.0 2003 radiosurgery Mean 8.4 3000 4.0 2.0 48 20/80 20/40 27.0

Conventional units: To convert minimum apex dose to rad, multiply centigray by 1.

RESULTS COMMENT

Five patients with symptomatic circumscribed choroi- Circumscribed choroidal hemangioma is a vascular tumor dal hemangiomas were treated by 103Pd brachytherapy. that can cause permanent loss of vision by leakage of The mean age in this group was 55 years (range, 45-70 subretinal fluid, associated retinal detachment, and cystoid years). Follow-up was documented during a mean in- degenerationoftheretina.4 Managementbecomesmoreprob- terval of 18.6 months (range, 6-29 months). The mean lematic with large or anteriorly located tumors, lesions as- height of all tumors was 3.3 mm as measured by ultra- sociated with extensive bullous retinal detachment, or tu- sound (range, 2.5-4.0 mm) (Table 2). All tumors de- mors located in proximity to the optic nerve or fovea. creased in height (to a mean of 1.7 mm) (Figure). No Laser photocoagulation will typically reduce the exuda- tumor recurrence was noted. tive subretinal fluid, but recurrences are common and as- All tumor-associated retinal detachments resolved sociated with vision loss.5 Recently, Schmidt-Erfurth et al,7,8 within the reported follow-up period (Figure). Visual Madreperla,6 Robertson,15 andotherresearchershavereported acuity improved in 4 (80%) of 5 patients after treat- on PDT in treatment of symptomatic circumscribed choroi- ment, and 1 patient’s visual acuity remained stable at dal hemangiomas.16-20 On average, 2 PDT treatments were 20/32 (with resolution of metamorphopsia). Twenty- required to control exudation of subretinal fluid. Overall, four months after treatment, 1 patient whose visual 60 patients were treated and 51 had an improvement in vi- acuity had recovered from 20/160 to 20/32 had a loss of sual acuity (mean, 3.3 lines) after PDT (Table 3). Tumors vision to 20/160 because of radiation maculopathy. At were noted to decrease from a mean pretreatment tumor the last follow-up, 3 patients (60%) retained their post- height of 3.0 mm to 0.4 mm at the last follow-up measure- operative best-corrected visual acuity. For all patients, a ment. It is important to note that problems associated with mean visual acuity improvement of 2 lines was docu- PDT for large vascular lesions have included focal overtreat- mented (95% confidence interval, 0.23-0.88) (Table 2). ment, leading to chorioretinal atrophy and resultant visual Compared with the results after other radiotherapy field defects.8 Photodynamic therapy is not practical for treat- techniques, no new complications could be attributed ment of large or anteriorly located hemangiomas. Clearly, to the use of 103Pd. PDT relies on the visualization of the hemangioma to aim

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 the sensitizing laser spot and to provide complete coverage a mean decrease of 50% (from 3.3 to 1.7 mm after treat- of the lesion. Therefore, if a tumor is hidden beneath a large ment). serous retinal detachment, treatment of the tumor by PDT This pilot study shows that a single 103Pd ophthalmic becomes problematic. In contrast, ophthalmic plaque radia- plaque radiation treatment is effective in eliminating sub- tion therapy is performed throughout the sclera and there- retinal fluid and improving vision in patients with symp- fore is not dependent on visualization of the tumor during tomatic circumscribed choroidal hemangiomas. treatment. Finally, unlike PDT, ophthalmic plaque brachy- therapy requires 2 surgical procedures. Submitted for Publication: July 31, 2003; final revision Several investigators reported favorable anatomic and received March 9, 2004; accepted April 21, 2004. visual results after external beam radiotherapy for choroi- Correspondence: Paul T. Finger, MD, New York Eye Can- dal hemangiomas (Table 4).10,12 They suggested that ex- cer Center, 115 E 61st St, New York, NY 10021 (pfinger ternal beam radiotherapy could be a useful therapeutic op- @eyecancer.com). tion for symptomatic choroidal hemangiomas.24 However, Funding/Support: This work was supported by The Eye- when compared with plaque brachytherapy, external beam Care Foundation and Research to Prevent Blindness, both radiotherapy distributes radiation over a larger area, poten- in New York, NY. tially increasing the risk of radiation-induced keratocon- junctivitis sicca, cataract, retinopathy, or optic neuropathy. 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In this series, the mean best-corrected Early Treatment 26. Packer S, Stoller S, Lesser ML, Mandel FS, Finger PT. Long-term results of iodine- Diabetic Retinopathy Study visual acuity at the last fol- 125 irradiation of uveal melanoma. Ophthalmology. 1992;99:767-774. low-up improved by 2 lines. All patients had complete reso- 27. Sealy R, Le Roux PL, Rapley F, Hering E, Shackleton D, Sevel D. The treatment of ophthalmic tumors with low-energy sources. Br J Radiol. 1976;49:551-554. lution of subretinal fluid with reattachment of the retina 28. Finger PT, Berson A, Szechter A. Palladium-103 plaque radiotherapy for choroi- after a single treatment. All tumors decreased in height, with dal melanoma. Ophthalmology. 1999;106:606-613.

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