Due to poor air quality related to fires in California, the Academy’s San Francisco offices will be closed Friday, Nov. 16. Member support staff will not be available by phone and responses to emails may be delayed.

  • Ocular Pathology/Oncology, Retina/Vitreous

    Authors: Loh-Shan Leung, MD; Mark S. Blumenkranz, MD

    Photodynamic therapy (PDT) has been used with success in the treatment of intraocular neoplasms, including vascular tumors such as choroidal hemangioma, choroidal osteoma, and as adjuvant therapy for choroidal melanoma.

    Choroidal Osteoma

    Choroidal osteoma is a rare benign osseous tumor most commonly affecting females in their second and third decades. The tumor itself is composed of mature bony tissue, with trabeculae, cavernous spaces, and capillaries. Frequently present in the juxtapapillary retina, the tumor may extend into the fovea, leading to vision loss, particularly when choroidal neovascularization develops. Additionally, with decalcification (which may occur spontaneously over a period of years, or as a result of treatment), RPE atrophy develops with secondary outer retinal degeneration.

    The goal of treatment of choroidal osteoma is to induce decalcification in extrafoveal tumors and to maintain calcification in subfoveal tumors, as well as reduce vision loss due to other complications, such as subretinal hemorrhage and choroidal neovascularization (CNV). When CNV is present, PDT may be used to cause involution; this has been reported in isolated case reports. Additionally, the tumor itself may be decalcified with PDT treatment. Authors in a recent case report were careful to recommend this therapy only in extrafoveal tumors, as subfoveal decalcification is not desirable for reasons stated above.

    Choroidal Hemangioma

    Choroidal hemangioma is a vascular hamartoma found in both diffuse and circumscribed forms. The diffuse form is typically associated with Sturge-Weber Syndrome, and is sometimes referred to descriptively as “tomato-catsup fundus.” Circumscribed choroidal hemangiomata usually have no systemic associations, and are most commonly found unilaterally as an orange or red mass in the posterior fundus, elevated, occasionally with overlying orange pigment, cystoid edema, or surrounding exudation. The diagnosis may be found on routine eye evaluation or if symptoms become manifest. Serous retinal detachment above the tumor is present in up to 81% of cases and is often the cause of visual symptoms (usually metamorphopsia or decreasing acuity). Circumscribed hemangiomata are usually more responsive to treatment.

    Although observation of choroidal hemangioma is the favored management in the vast majority of cases, if subfoveal fluid, exudative retinal detachment, or cystoid edema threatens vision, intervention is indicated. A number of reports have described successful resolution of subretinal and intraretinal fluid following PDT. Additionally, tumor regression is a frequent consequence of PDT, and angiography has been used to document regression or closure of the vasculature within the tumor. Vision often stabilizes, or more often improves, after resolution of exudation, subsensory fluid, or macular edema. One of the largest series of PDT for choroidal hemangioma prospectively followed 31 eyes for at least 12 months, showing resolution of exudation and subretinal and intraretinal fluid in 93% of cases, with visual improvement in 69% and visual stability in 27%. Other studies have shown comparable results, with success rates of fluid and tumor regression in greater than 85% of cases. Variable treatment regimens have been described, with fluence ranging from 50-100 J/cm2, and with the number of treatments determined by subsequent examinations. In these relatively small case series, no serious adverse events have been reported, although significant retinal pigment epithelial alterations have been described, particularly with larger light doses or bolus doses of verteporfin, and one case of transient choroidal effusion and perifoveal hemorrhage resulted in subsequent visual acuity loss.

    Choroidal Melanoma

    Photodynamic therapy has also been advocated as an additional therapy for choroidal melanoma. In an initial series of patients who had failed plaque brachytherapy and transpupillary thermotherapy, verteporfin PDT was attempted as globe salvaging therapy, sparing 2 out of the 4 eyes from enucleation. Others have reported the use of PDT as a primary therapy, particularly in amelanotic melanoma, as well as in posterior tumors close to the macula, citing the high likelihood of vision loss due to radiation maculopathy, as well as the difficulty in plaque placement as reasons traditional therapies might be ineffective. A published series reported complete regression in 8 of 9 patients receiving PDT for posteriorly located amelanotic melanoma, with none developing metastatic disease with up to 90 months of follow up.

    Although there is no standardized treatment protocol for PDT in melanoma, typical PDT application for melanoma involves a 5- to 10-minute infusion of a standard dose of verteporfin (6 mg/m2), followed by laser treatment with fluence of 50-100 J/cm2 (either 83 or 166 seconds). The treatment area encompasses the entire tumor with a 1 mm margin of normal choroid (except in juxtapapillary tumors, where direct treatment of the nerve is avoided). The decision to reapply laser is typically made after several months of observation, with multiple treatments sometimes required.

    Adverse events include ocular pain and inflammation (likely resulting from tumor necrosis), as well as hemorrhage within the tumor or serous retinal detachment. In posterior tumors, PDT has the advantage of being potentially less destructive to vision. However, with limited data on this therapy for melanoma, its role still needs to be clarified.

    Despite the expanding indications for intravitreal anti-VEGF therapy, PDT remains an important part of the therapeutic armamentarium. Particularly for vascular lesions, its primary advantage lies in its persistent effect over a period of months. In contrast, intravitreal injection therapy frequently requires retreatment monthly, leading to significant psychological and financial burden, in addition to the cumulative risk of infection, retinal detachment, and other associated systemic side effects over the treatment lifetime of a patient. Finally, despite the reputation of anti-VEGF therapy as “cure-all” for any number of retinal and choroidal vascular disorders, certain conditions appear to be more responsive to PDT.

    Suggested Reading

    1. Rosen E. Letter: "Tomato-catsup" fundus in Sturge-Weber syndrome. Arch Ophthalmol. 1974;92(6):537.
    2. Shields CL, Honavar SG, Shields JA, Cater J, Demirci H. Circumscribed choroidal hemangioma: clinical manifestations and factors predictive of visual outcome in 200 consecutive cases. Ophthalmology. 2001;108(12):2237-2248.
    3. Witschel H, Font RL. Hemangioma of the choroid. A clinicopathologic study of 71 cases and a review of the literature. Surv Ophthalmol. 1976;20(6):415-431.
    4. Shields CL, Materin MA, Marr BP, Mashayekhi A, Shields JA. Resolution of advanced cystoid macular edema following photodynamic therapy for choroidal hemangioma. Ophthalmic Surg Lasers Imaging. 2005;36(3):237-239.
    5. Porrini G, Giovannini A, Amato G, Ioni A, Pantanetti M. Photodynamic therapy of circumscribed choroidal hemangioma. Ophthalmology. 2003;110(4):674-680.
    6. Boixadera A, García-Arumí J, Martínez-Castillo V, et al. Prospective clinical trial evaluating the efficacy of photodynamic therapy for symptomatic circumscribed choroidal hemangioma. Ophthalmology. 2009;116(1):100-105.
    7. Blasi MA, Tiberti AC, Scupola A, et al. Photodynamic therapy with verteporfin for symptomatic circumscribed choroidal hemangioma: five-year outcomes. Ophthalmology. 2010;117(8):1630-1637.
    8. Schmidt-Erfurth UM, Michels S, Kusserow C, Jurklies B, Augustin AJ. Photodynamic therapy for symptomatic choroidal hemangioma: visual and anatomic results. Ophthalmology. 2002;109(12):2284-2294.
    9. Jurklies B, Anastassiou G, Ortmans S, et al. Photodynamic therapy using verteporfin in circumscribed choroidal haemangioma. Br J Ophthalmol. 2003;87(1):84-89.
    10. Landau IM, Steen B, Seregard S. Photodynamic therapy for circumscribed choroidal haemangioma. Acta Ophthalmol Scand. 2002;80(5):531-536.
    11. Barbazetto IA, Lee TC, Rollins IS, Chang S, Abramson DH. Treatment of choroidal melanoma using photodynamic therapy. Am J Ophthalmol. 2003;135(6):898-899.
    12. Donaldson MJ, Lim L, Harper CA, Mackenzie J, G Campbell W. Primary treatment of choroidal amelanotic melanoma with photodynamic therapy. Clin Experiment Ophthalmol. 2005;33(5):548-549.
    13. Campbell WG, Pejnovic TM. Treatment of amelanotic choroidal melanoma with photodynamic therapy. Retina. 2012;32(7):1356-1362.