From Istanbul University (ST, NK), Istanbul Faculty of Medicine, Department of Ophthalmology, Istanbul, Turkey; and the Ocular Oncology Service (CLS), Wills Eye Institute, Philadelphia, Pennsylvania.
The authors have no financial or proprietary interest in the materials presented herein.
The authors thank Nurgün Demir for her assistance in collecting the data of the patient for this study.
Address correspondence to Samuray Tuncer, MD, Istanbul University, Istanbul Faculty of Medicine, Department of Ophthalmology, Capa 34390, Istanbul, Turkey. E-mail: email@example.com
Plaque radiotherapy is designed as an eye-conserving treatment for intraocular tumors. Because the mortality rates following iodine (I125) plaque radiotherapy are similar to rates following enucleation in tumors with appropriate size and location, it has assumed a major role in the management of choroidal melanoma.1 Iodine plaque radiotherapy combined with thermotherapy has demonstrated remarkable local tumor control at 97% by 5-year follow-up. Patients with prominent residual or recurrent melanoma following treatment are often treated with enucleation, repeat plaque radiotherapy, or heavy thermotherapy.2,3
Photodynamic therapy (PDT) is an alternative treatment for selected choroidal melanoma. Initial reports on PDT for choroidal melanoma were disappointing, with failure in 3 of 4 eyes, all of which displayed pigmented melanoma.4 Later studies using verteporfin PDT as primary treatment revealed success in all nine patients with nonpigmented choroidal melanoma.5 We report our experience with PDT for a patient who failed standard I125 brachytherapy for amelanotic choroidal melanoma.
A 40-year-old woman developed blurred vision in the right eye over 5 months. She was amblyopic in the left eye. Visual acuity was 20/20 in the right eye and 20/100 in the left eye. Funduscopy revealed an amelanotic choroidal melanoma located inferonasally and measuring 9 mm in basal dimension and 6.5 mm in thickness. Fluorescein angiography confirmed intrinsic tumor vascularity and ultrasonography showed acoustic hollowness, consistent with melanoma (Figs. 1A and 1B). Systemic work-up was negative for metastasis.
Figure 1. Before photodynamic therapy (PDT): (A) Fundus photograph of the right eye shows an amelanotic choroidal melanoma located inferonasally. (B) Ultrasonography demonstrates a hollow choroidal lesion 6.5 mm in thickness. After PDT: (C) Two months after PDT, the tumor regressed, leaving an atrophic scar. Localized choroidal hemorrhage appeared as the only minor complication of PDT. (D) Fundus photograph taken at 34 months of follow-up shows that the tumor is completely regressed, leaving an atrophic chorioretinal scar. Note cotton-wool spots over the optic disc and papilledema in the superior half of the optic disc due to radiation papillopathy. (E) Ultrasonography reveals a regressed choroidal tumor, 1.3 mm in thickness. (F) Fundus fluorescein angiography shows that the choroidal melanoma was totally regressed. Note the selective destruction of the choroidal tumor and sparing of the retinal vessels over the treated area.
The tumor was treated with I125 brachytherapy using an apical dose of 80 Gy. The tumor showed poor response with no change in thickness, remaining at 6.5 mm at 16 months of follow-up. There was concern for residual viable tumor so options of enucleation, repeat plaque radiotherapy, transpupillary thermotherapy, and PDT were considered. Given the juxtapapillary location and amelanotic appearance, PDT was advised.
The residual tumor was treated with PDT using standard treatment parameters. An intravenous injection of 6 mg/m2 body surface area of verteporfin over 10 minutes was performed and laser treatment with emission wavelength at 689 nm was delivered to the entire tumor in three overlapping spots (8,600 microns), with avoidance of the optic disc. Treatment parameters were 50 J/cm2 light dose, 600 mW/cm2 power, and 83 seconds duration.
Two months following one session of PDT, the tumor was completely flat, measuring 1.3 mm thickness and demonstrating complete atrophy and no residua. A localized choroidal hemorrhage in the superior portion of the regressed scar resolved over 2 months (Fig. 1C). At 50 months of follow-up, visual acuity remained 20/25 with complete tumor atrophy and no metastatic disease (Figs. 1D, 1E, and 1F).
PDT has been used for treatment of various intraocular tumors, including choroidal hemangioma,6 osteoma,7 exudative changes over nevus,8 and melanoma.4,9,10 In 1984, PDT with photosensitizer hematoporphyrin was used for treatment of melanoma, but poor tissue penetration and lack of dye selectivity led to suboptimal tumoricidal activity and significant intraocular complications.11 Recent studies using a different photosensitizer with PDT, namely benzoporphyrin derivative (verteporfin), have shown encouraging results in animal studies of choroidal melanoma12 and been used as primary and secondary treatment of choroidal melanoma.4,9,10
In 2003, Barbazetto et al. described four patients with pigmented choroidal melanoma treated with verteporfin PDT.4 Complete tumor control was achieved in only one case, whereas the other three cases failed and showed progressive enlargement. It was speculated that failure was related to poor PDT uptake due to tumor pigmentation. In 2005, Donaldson et al. described treatment of a 3.7-mm thick, extrafoveal amelanotic melanoma with verteporfin PDT.9 Complete tumor control was achieved following four PDT sessions over 12 months. There was limited response to the first treatment session using standard parameters, but the subsequent three PDT sessions were applied with different parameters (1 minute injection bolus, 100 J/cm2 light dose, and 166 seconds exposure). In 2006, Soucek and Cihelkova reported complete regression of subfoveal amelanotic choroidal melanoma following verteporfin PDT.10 At the International Society of Ocular Oncology meeting in 2009, Campbell and Pejnovic presented their results of verteporfin PDT in nine patients with amelanotic choroidal melanomas, one of which had a pigmented portion.5 In their series, all nine tumors demonstrated a response to PDT. Four flattened after a single session, four required three treatments, and in one case it was necessary to apply PDT four times to achieve complete tumor regression. In eight patients there was no evidence of recurrence during total follow-up between 19 and 76 months. One patient with a partially pigmented tumor developed a small local recurrence at 21 months, and responded to a further application of PDT. These studies show that PDT is effective in causing regression of amelanotic choroidal melanoma.5,9,10
In our case, verteporfin PDT was used as a secondary treatment, following poor response to brachytherapy. Using one session of PDT with standard parameters, the melanoma showed dramatic regression over 2 months to a completely flat scar and was stable over 4 years of follow-up. There were no reactive retinal pigment epithelial changes surrounding the treatment site and the overlying retinal vessels were spared.
We believe that radiotherapy is the most effective conservative treatment for uveal melanoma. However, in selective amelanotic choroidal melanoma, particularly those with incomplete response to brachytherapy, verteporfin PDT may provide consolidation.
- Shields CL, Furuta M, Thangappan A, et al. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol. 2009;127:989–998. doi:10.1001/archophthalmol.2009.208 [CrossRef]
- Shields CL, Cater J, Shields JA, et al. Combined plaque radiotherapy and transpupillary thermotherapy for choroidal melanoma: tumor control and treatment complications in 270 consecutive patients. Arch Ophthalmol. 2002;120:933–940.
- Shields JA, Shields CL. Posterior uveal melanoma: management. In: Shields JA, Shields CL, eds. Intraocular Tumors: An Atlas and Textbook, 2nd ed. Philadelphia: Lippincott, Williams & Wilkins; 2008:140–175.
- Barbazetto IA, Lee TC, Rollins IS, Chang S, Abramson DH. Treatment of choroidal melanoma using photodynamic therapy. Am J Ophthalmol. 2003;135:898–899. doi:10.1016/S0002-9394(02)02222-5 [CrossRef]
- Campbell WG, Pejnovic TM. Treatment of choroidal amelanotic melanoma with PDT. Presented at: The International Society of Ocular Oncology Meeting. ; September 9, 2009. ; Cambridge, England. . Abstract:164.
- Blasi MA, Tiberti AC, Scupola A, et al. Photodynamic therapy with verteporfin for symptomatic circumscribed choroidal hemangioma: five-year outcomes. Ophthalmology. 2010;117:1630–1637. doi:10.1016/j.ophtha.2009.12.033 [CrossRef]
- Shields CL, Materin MA, Mehta S, Foxman BT, Shields JA. Regression of extrafoveal choroidal osteoma following photodynamic therapy. Arch Ophthalmol. 2008;126:135–137. doi:10.1001/archopht.126.1.135 [CrossRef]
- Rundle P, Rennie I. Management of symptomatic choroidal naevi with photodynamic therapy. Eye (Lond). 2007;21:1531–1533. doi:10.1038/sj.eye.6702623 [CrossRef]
- Donaldson MJ, Lim L, Harper CA, Mackenzie JG, Campbell W. Primary treatment of choroidal amelanotic melanoma with photodynamic therapy. Clin Experiment Ophthalmol. 2005;33:548–549. doi:10.1111/j.1442-9071.2005.01083.x [CrossRef]
- Soucek P, Cihelkova I. Photodynamic therapy with verteporfin in subfoveal amelanotic choroidal melanoma (a controlled case). Neuro Endocrinol Lett. 2006;27:145–148.
- Tse DT, Dutton JJ, Weingeist TA, Hermsen VM, Kersten RC. Hematoporphyrin photoradiation therapy for intraocular and orbital malignant melanoma. Arch Ophthalmol. 1984;102:833–838. doi:10.1001/archopht.1984.01040030653011 [CrossRef]
- Young LH, Howard MA, Hu LK, Kim RY, Gragoudas ES. Photodynamic therapy of pigmented choroidal melanomas using a liposomal preparation of benzoporphyrin derivative. Arch Ophthalmol. 1996;114:186–192. doi:10.1001/archopht.1996.01100130180013 [CrossRef]