Palladium 103 (103Pd) Plaque Radiation Therapy for CircumscribedChoroidal Hemangioma With Retinal Detachment

Objective  To describe clinical experience with palladium 103 (¹⁰³Pd)ophthalmic plaque radiotherapy for choroidal hemangioma.

Methods  One course of ¹⁰³Pd ophthalmic plaque radiotherapy was usedin each of 5 patients with circumscribed choroidal hemangioma who had progressiveloss of vision due to subretinal exudation. A mean apex dose of 2900 cGy (2900rad) was delivered. Functional tests of outcome included best-corrected visualacuity. Anatomic results included changes in tumor height and subretinal fluiddocumented by ophthalmoscopy, fluorescein angiography, and ultrasonography.

Results  All patients had complete resolution of subretinal fluid with reattachmentof the retina. All tumors decreased in height (mean, 50%) after treatment.Three patients (60%) demonstrated improvement in visual acuity at the lastfollow-up, and in 1 patient vision remained stable with resolution of metamorphopsia.Twenty-four months after treatment, 1 patient whose visual acuity had recoveredfrom 20/160 to 20/32 had a loss of vision to 20/160 because of radiation maculopathy.For all patients, a mean visual acuity improvement of 2 lines was documented(95% confidence interval, 0.23-0.88). Mean follow-up was 18.6 months (range,6-29 months).

Conclusions  A single ¹⁰³Pd plaque radiation treatment was effective indecreasing tumor height, eliminating subretinal fluid, and improving visualacuity in patients with symptomatic circumscribed choroidal hemangiomas.

Circumscribed choroidal hemangioma is a benign vascular tumor that typicallyappears as a subtle, amelanotic, red-orange mass in the posterior pole.¹ Mild yellow-white foci on the tumor surface may bepresent and represent fibrous metaplasia of the overlying retinal pigmentepithelium.² Visual acuity loss typically resultsfrom intraretinal edema, cystoid degeneration, and accumulation of subretinalfluid. Massive exudation may lead to serous retinal detachment.³

Various treatment modalities have been described for symptomatic choroidalhemangiomas and have included penetrating diathermy, xenon photocoagulation,argon laser photocoagulation, microwave hyperthermia, external beam radiotherapy,infrareddiode laser thermotherapy, photodynamic therapy, stereotactic radiotherapy,and radioactive plaque therapy.^3-14

Laser photocoagulation was previously widely used to treat choroidalhemangiomas. The photocoagulation was scattered over the tumor’s surfaceto reduce associated subretinal fluid.⁵ Becauseof recurrence of retinal detachments, multiple treatments were required andthe long-term visual prognosis was poor.^3-5 Morerecently, various researchers have reported successful treatments of symptomaticcircumscribed choroidal hemangiomas by photodynamic therapy (PDT).^6-8,15-20

Several researchers have also reported successful treatment of diffuseand circumscribed choroidal hemangiomas with radiation therapy.^9,10,12,13 In1996, Zographos et al⁹ investigated cobalt60 (60Co) brachytherapy and suggested that radiotherapy was the best therapeuticmodality for the treatment of large hemangiomas, those that involve the maculararea, and hemangiomas associated with a bullous secondary exudative retinaldetachment. Madreperla et al¹⁰ found that inpatients with circumscribed choroidal hemangiomas treated with iodine I 125(¹²⁵I) or ruthenium 106 (¹⁰⁶Ru) brachytherapy, 75% hadvisual acuity of 20/40 or better at 1 year, and they noted resolution of subretinalfluid in 100% of cases. Most recently, Kivela et al¹⁴ reportedtheir experience with stereotactic radiosurgery for circumscribed choroidalhemangioma. They noted resolution of subretinal fluid in all patients andsuggested that stereotactic therapy be targeted to small and posteriorly locatedcircumscribed choroidal hemangiomas.¹⁴

In 1989, palladium 103 (¹⁰³Pd) seeds became available forbrachytherapy.²¹ Comparative studies have shownthat when equivalent target doses were prescribed, the use of ¹⁰³Pdresulted in an increased dose within the targeted zone (tumor) and less radiationto most normal ocular tissues compared with ¹²⁵I.²² An11-year study of ¹⁰³Pd plaque radiotherapy for choroidal melanomafound better visual function outcomes compared with the results from centersusing ¹²⁵I.²³

Herein are reported what we believe to be the first visual and anatomicresults of a series of patients with symptomatic choroidal hemangiomas treatedwith ¹⁰³Pd ophthalmic plaque radiotherapy.

A prospective, nonrandomized clinical study was conducted in 5 consecutivepatients with previously untreated and symptomatic circumscribed choroidalhemangioma. The diagnosis was made by clinical ophthalmoscopic, fluoresceinangiographic, and ultrasonographic features. Each patient participated ina detailed discussion of the risks and benefits of various therapeutic modalities.All patients signed a statement of informed consent. Institutional reviewboard approval was not considered necessary because of the established useof radiation therapy for choroidal hemangiomas.

Clinical history included the patient’s age, sex, and medicalhistory. Ophthalmic evaluations included a best-corrected visual acuity andpupillary, oculomotor, and slitlamp examinations. Goldmann tonometry was usedto measure intraocular pressure. The basal dimensions of the tumors were determinedby ophthalmoscopy, fluorescein angiography, transillumination, and B-scanultrasonography. A-scan ultrasonography was used to measure the height ofthe tumor and internal reflectivity. B-scan ultrasonography was typicallyused to determine tumor location and shape and evidence of retinal detachments.Fluorescein angiography and fundus photography were used to evaluate and recordpatterns of tumor circulation, focal leakage, cystoid macular edema, and radiationretinopathy.

The clinical data were analyzed with regard to improvement in visualacuity after treatment. The SPSS software package, version 11.01 (SPSS Inc,Chicago, Ill), was used for data analysis. The modified Wald test was usedto calculate 95% confidence interval.

Palladium 103 seeds were available at strengths of up to 5 mCi (185MBq) per seed (model 200; Theragenics Corp, Buford, Ga). The cylindrical titanium-encapsulated ¹⁰³Pd seeds measured 0.8 mm in diameter and 4.5 mm in length. Seedswere affixed into standard COMS (Collaborative Ocular Melanoma Study)–typegold plaques (Trachsel Dental Studio Inc, Rochester, Minn) with a thin layerof medical-grade acrylic fixative. Because of low energy of x-rays from ¹⁰³Pd, the 0.5-mm-thick plaque blocked more than 99% of photons directedto the sides of and posterior to the plaque.²² Ourmethods of ¹⁰³Pd plaque dosimetry have been described elsewhere.^22,23

In this series, all patients received 1 radiation treatment. Eye plaqueswere sewn to the episclera to cover the base of the intraocular tumor, radiationwas continuously delivered during 2 to 5 days, and the plaques were removed.The tumor apex served as the radiation prescription point. Treatment timeand dose rate were calculated on the basis of the dimensions of the tumorsand followed COMS guidelines, whereby the apex dose rate was kept between50 and 125 cGy/h (50 and 125 rad/h). Similarly, a treatment margin of 2 mmwas included around the edges of the tumor. The mean apex dose for the 5 patientswho were treated with ¹⁰³Pd was 2900 cGy (2900 rad) (Table 1).

Five patients with symptomatic circumscribed choroidal hemangiomas weretreated by ¹⁰³Pd brachytherapy. The mean age in this group was55 years (range, 45-70 years). Follow-up was documented during a mean intervalof 18.6 months (range, 6-29 months). The mean height of all tumors was 3.3mm as measured by ultrasound (range, 2.5-4.0 mm) (Table 2). All tumors decreased in height (to a mean of 1.7 mm) (Figure). No tumor recurrence was noted.

All tumor-associated retinal detachments resolved within the reportedfollow-up period (Figure). Visual acuityimproved in 4 (80%) of 5 patients after treatment, and 1 patient’s visualacuity remained stable at 20/32 (with resolution of metamorphopsia). Twenty-fourmonths after treatment, 1 patient whose visual acuity had recovered from 20/160to 20/32 had a loss of vision to 20/160 because of radiation maculopathy.At the last follow-up, 3 patients (60%) retained their postoperative best-correctedvisual acuity. For all patients, a mean visual acuity improvement of 2 lineswas documented (95% confidence interval, 0.23-0.88) (Table 2). Compared with the results after other radiotherapy techniques,no new complications could be attributed to the use of ¹⁰³Pd.

Circumscribed choroidal hemangioma is a vascular tumor that can causepermanent loss of vision by leakage ofsubretinal fluid, associated retinaldetachment, and cystoid degeneration of the retina.⁴ Managementbecomes more problematic with large or anteriorly located tumors, lesionsassociated with extensive bullous retinal detachment, or tumors located inproximity to the optic nerve or fovea.

Laser photocoagulation will typically reduce the exudative subretinalfluid, but recurrences are common and associated with vision loss.⁵ Recently, Schmidt-Erfurth et al,^7,8 Madreperla,⁶ Robertson,¹⁵ and otherresearchers have reported on PDT in treatment of symptomatic circumscribedchoroidal hemangiomas.^16-20 Onaverage, 2 PDT treatments were required to control exudation of subretinalfluid. Overall, 60 patients were treated and 51 had an improvement in visualacuity (mean, 3.3 lines) after PDT (Table 3).Tumors were noted to decrease from a mean pretreatment tumor height of 3.0mm to 0.4 mm at the last follow-up measurement. It is important to note thatproblems associated with PDT for large vascular lesions have included focalovertreatment, leading to chorioretinal atrophy and resultant visual fielddefects.⁸ Photodynamic therapy is not practicalfor treatment of large or anteriorly located hemangiomas. Clearly, PDT relieson the visualization of the hemangioma to aim the sensitizing laser spot andto provide complete coverage of the lesion. Therefore, if a tumor is hiddenbeneath a large serous retinal detachment, treatment of the tumor by PDT becomesproblematic. In contrast, ophthalmic plaque radiation therapy is performedthroughout the sclera and therefore is not dependent on visualization of thetumor during treatment. Finally, unlike PDT, ophthalmic plaque brachytherapyrequires 2 surgical procedures.

Several investigators reported favorable anatomic and visual resultsafter external beam radiotherapy for choroidal hemangiomas (Table 4).^10,12 Theysuggested that external beam radiotherapy could be a useful therapeutic optionfor symptomatic choroidal hemangiomas.²⁴ However,when compared with plaque brachytherapy, external beam radiotherapy distributesradiation over a larger area, potentially increasing the risk of radiation-inducedkeratoconjunctivitis sicca, cataract, retinopathy, or optic neuropathy.

Recently, Kivela et al¹⁴ reported a seriesof 5 patients with symptomatic circumscribed choroidal hemangiomas treatedwith stereotactic radiotherapy. In their series, 1 patient lost 7 lines ofbest-corrected visual acuity at 26 months and 4 patients were within 2 linesat 20 months of follow-up.¹⁴ The relativelyhigh cost of stereotactic radiotherapy must be considered in the current eraof cost-effectiveness.

In 1966, Stallard²⁵ introduced the firstradioactive ophthalmic plaques (⁶⁰Co). Packer et al²⁶ andSealy et al²⁷ noted that when compared with60Co,the much lower-energy photons (28 keV) emitted from ¹²⁵I plaqueswere more rapidly absorbed in tissue and, therefore (for equivalent apex dose),reached fewer normal ocular structures. In this series, ¹⁰³Pd offeredeven lower-energy photons than ¹²⁵I and greater tissue penetrationthan106Ru.²⁸ Therefore, a switch from ¹²⁵I to ¹⁰³Pd seeds increased irradiation of the tumor, whilesimultaneously decreasing the amount of radiation to most normal ocular structuresoutside the targeted zone.^22,23,28 Inaddition, an 11-year study of ¹⁰³Pd plaque radiotherapy for choroidalmelanoma showed better visual results than those from centers using ¹²⁵I.²³ This is why we chose to use ¹⁰³Pd for this study of plaque radiation for medium-sized choroidalhemangiomas. If we were to treat larger hemangiomas (ie, >8 mm in height),we would choose the radiation treatment modality on the basis of comparativedosimetry.²³ We expect that patterns of secondaryradiation complications can be predicted by dosimetry studies, but proofsof these differences will require a large comparative clinical trial.

This study describes the first (to our knowledge) clinical experiencewith ¹⁰³Pd ophthalmic plaque radiotherapy for symptomatic choroidalhemangioma. Anatomic and functional outcomes were documented for up to 29months (mean, 18.6 months) of follow-up. Limitations of this study includethe small number of patients and a relatively short follow-up. With longer-termfollow-up, it is possible that radiation maculopathy may affect the visualacuity of patients irradiated for posterior uveal tumors (as seen in 1 patientin this study).

In this series, the mean best-corrected Early Treatment Diabetic RetinopathyStudy visual acuity at the last follow-up improved by 2 lines. All patientshad complete resolution of subretinal fluid with reattachment of the retinaafter a single treatment. All tumors decreased in height, with a mean decreaseof 50% (from 3.3 to 1.7 mm after treatment).

This pilot study shows that a single ¹⁰³Pd ophthalmic plaqueradiation treatment is effective in eliminating subretinal fluid and improvingvision in patients with symptomatic circumscribed choroidal hemangiomas.

Correspondence: Paul T. Finger, MD, NewYork Eye Cancer Center, 115 E 61st St, New York, NY 10021 (pfinger@eyecancer.com).

Financial Disclosure: None.

Submitted for Publication: July 31, 2003; finalrevision received March 9, 2004; accepted April 21, 2004.

Funding/Support: This work was supported byThe EyeCare Foundation and Research to Prevent Blindness, both in New York,NY.