Photodynamic therapy of symptomatic choroidal nevi.

PURPOSE: To evaluate the role of photodynamic therapy (PDT) for patients with symptomatic choroidal nevi involving the fovea or located near the fovea with subretinal fluid extending to the fovea.
MATERIALS AND METHODS: Retrospective review of five patients who underwent PDT for choroidal nevi at two separate centers in Ankara and Barcelona.
RESULTS: The mean initial logMAR visual acuity was 0.5 (range: 0 to 1.5). The mean largest tumor base diameter was 3.2 mm (range: 2.1-4.5 mm) and the mean tumor thickness was 1.1 mm (range: 0.7-1.6 mm). The mean number of PDT sessions was 1.6 (range:1-3). The mean final tumor thickness was 1.0 mm (range: 0-1.6 mm) at a mean follow-up of 19 months (range: 12-32 months). The mean final logMAR visual acuity was 0.4 (range: 0-1.5). Subfoveal fluid disappeared or decreased significantly in 4 of 5 eyes (80%) after PDT.
CONCLUSIONS: PDT led to resolution of subretinal fluid with preservation of visual acuity in many symptomatic choroidal nevi in this study. Careful case selection is important as PDT of indeterminate pigmented tumors may delay the diagnosis and treatment of an early choroidal melanoma and thereby increase the risk for metastasis.

INTRODUCTION

The treatment of symptomatic choroidal nevi either subfoveal or located near the fovea with subretinal fluid extending to the fovea presents a challange. Although the majority of choroidal nevi are asymptomatic, approximately 11% of these cases become symptomatic later for a number of reasons including subretinal fluid and choroidal neovascularization.1 These symptomatic choroidal nevi need to be treated to prevent progressive visual loss. Various treatments have been tried for choroidal nevi located under or near the fovea including laser photocoagulation and transpupillary thermotherapy (TTT).23 Delimiting or ablative laser photocoagulation has been used in the treatment of sensory detachment of the fovea and TTT has been used in the treatment of choroidal neovascularization associated with choroidal nevus. Transpupillary thermotherapy may result in the development of epiretinal membranes and cystoid macular edema leading to poor visual acuity.4

Over the past years, photodynamic therapy (PDT) using verteporfin has been used for an increasing number of ophthalmic diseases including choroidal neovascularization in age-related macular degeneration, presumed ocular histoplasmosis syndrome, pathologic myopia, and central serous choroidoretinopathy with or without choroidal neovascularization (CNV).5–10 It has also been used in a number of intraocular tumors including choroidal hemangioma, retinal capillary hemangioma, retinal vasoproliferative tumor, retinal astrocytoma, choroidal osteoma, choroidal nevus and choroidal melanoma.11–24 PDT has been used in the treatment of CNV and sensory detachment of the fovea associated with choroidal nevus.22–24 Because PDT is a relatively well-tolerated treatment with little damage to the visually important structures, we offered PDT for patients with symptomatic choroidal nevi either subfoveal or located near the fovea with subretinal fluid extending to the fovea. We are aware of at least one paper in the literature so far discussing the use of PDT in this role.22

MATERIALS AND METHODS

Medical records of all patients who underwent PDT for a choroidal nevus at two separate centers in Ankara and Barcelona were reviewed. The study was performed as per the tenets of the Declaration of Helsinki. Each patient underwent complete ocular examination including Snellen visual acuity and intraocular pressure measurement, anterior segment and fundus examinations, A and B mode ultrasonography, fluorescein angiography, optical coherence tomography, fundus autofluorescence and indocyanine green angiography where available. All patients were assessed with respect to the risk factors for growth including lipofuscin pigment, symptoms, peripapillary location, subretinal fluid (SRF), and thickness > 2 mm.

Standard fluence PDT was administered in all patients. A single intravenous dose of verteporfin (6 mg/m2) was infused over 10 min. Five minutes following the infusion, diode laser (690 nm in wavelength) of 600 mW/cm2 intensity was applied to the surface of the choroidal nevus for 83 s per application. If a single spot was insufficient to cover the entire surface area of the lesion, then two overlapping spots were used. Although standard fluence PDT was used, the light energy may be increased in the area of overlapping spots.

Patients were followed up at three-month intervals and ancillary studies were done as necessary. Angiographic studies were not repeated at follow-up examinations unless there was a decrease in visual acuity. Repeat PDT applications were administered depending on the persistence of SRF.

RESULTS

A total of five patients with symptomatic choroidal nevi either subfoveal or located near the fovea with subretinal fluid extending to the fovea underwent PDT between February 2008 and January 2010. Patient demographics, tumor features, number of PDT sessions, and follow-up of these five patients are summarized in Tables 1 and 2. The mean age of the patients was 56.2 years, ranging from 48 to 74 years. None of the patients had systemic diseases including diabetes mellitus and hypertension. The mean initial logMAR visual acuity was 0.6 (range: 0 to 1.5). The mean largest tumor base diameter was 3.2 mm (range: 2.1–4.5 mm) and the mean tumor thickness was 1.1 mm (range: 0.7–1.6). The mean distance to the optic disc was 1.0 mm (range: 0–3.0). The tumor had a juxtapapillary location in three of five patients. The mean distance to the fovea was 0.4 mm (range: 0–1.2 mm). All patients demonstrated subretinal fluid involving the fovea and one patient had subfoveal fibrin deposition on OCT [Figure 1]. Two choroidal nevi had lipofuscin pigment on the tumor surface and one choroidal nevus had subretinal fibrosis. Two of five choroidal melanocytic lesions displayed four risk factors for growth, two of five choroidal melanocytic lesions had three risk factors, and one choroidal melanocytic lesion had two risk factors.

Table 1

Patient demographics, tumor features, and presence of symptoms in five patients with choroidal nevi treated with photodynamic therapy

Table 2

Tumor thickness, visual acuity, number of photodynamic therapy sessions, and follow-up in five patients with choroidal nevi treated with photodynamic therapy

Figure 1

Patient 4. Right eye. Color fundus photograph (a), mid phase fluorescein angiogram (b) and fundus autofluorescence photograph (c) of a 48-year-old male with a choroidal nevus demonstrating orange pigment on the lesion and subretinal fluid in the fovea. Optical coherence tomography (OCT) at baseline (d) shows the presence of intraretinal fluid and presumed fibrin collection. OCT after third photodynamic therapy (e) shows improvement in central retinal thickness with marked resolution of the intraretinal material and persistence of subretinal fluid at 24 months follow-up

The mean number of PDT sessions was 1.6 (range:1–3). The mean number of spots used in PDT sessions to cover the entire surface of the lesion was 1.3 (range: 1–2). The mean final tumor thickness was 1.0 mm (range: 0–1.5 mm) at a mean follow-up of 19 months (range: 12–32 months). Subfoveal fluid disappeared completely in two eyes [Figure 2], decreased considerably in two eyes, and there was no change in the amount of subfoveal fluid in one eye [Figure 1]. One patient (no 4) experienced visual acuity loss from 20/50 to 20/80. Increasing fibrous metaplasia seems to be primarily responsible for the vision decrease and fluorescein angiography did not demonstrate any sign of choroidal ischemia from repeated PDT applications in this case. One pigmented choroidal nevus shrank down to a flat scar and three pigmented and partially pigmented choroidal nevi remained stable in thickness after PDT. One pigmented choroidal nevus increased in thickness after the first PDT application but the thickness remained the same after the second PDT application. The final visual acuities ranged from counting fingers to 20/20. The mean final logMAR visual acuity was 0.4 (range: 0–1.5).

Figure 2

Patient 5. Left eye. Color fundus photograph (a), fluorescein angiogram (b) and ocular ultrasonogram (c) of a 74-year-old male with a peripapillary choroidal nevus with orange pigment over the lesion surface and subretinal fluid under the fovea. Optical coherence tomography (OCT) at baseline (d) shows the presence of subretinal fluid. OCT 3 months after a single session of photodynamic therapy (e) shows improvement in central retinal thickness and almost complete resolution of neurosensory retinal detachment

DISCUSSION

One of the critical decisions in ocular oncology pertains to the differentiation of choroidal nevus versus choroidal melanoma. Choroidal nevus tends to be a stable lesion with unchanged or minimally increased thickness and base diameter over a period of months and years. The appearance of subretinal fluid causes symptoms, thus creating a symptomatic nevus. None of the patients in our series had any pre-intervention follow-up to prove that their lesions had indeed been stable choroidal nevi. They all had symptomatic choroidal melanocytic lesions at presentation to us.

Many oncologists prefer to treat a choroidal melanocytic lesion demonstrating at least two out of the five risk factors for growth including lipofuscin pigment, symptoms, peripapillary location, subretinal fluid (SRF), and thickness > 2 mm in the hopes of eradicating a suspicious nevus that has at least a 50% risk of growing into a melanoma.25 All our cases displayed at least two risk factors for growth. However, none of the tumors included in this series exhibited growth over the follow-up of 12–32 months after PDT showing the stable nature of the indeterminate choroidal melanocytic lesions classified as nevi. Close monitoring for early detection of malignant transformation and further treatment is mandatory. It must be borne in mind that PDT of indeterminate pigmented tumors may delay the diagnosis and treatment of an early choroidal melanoma and thereby increase the risk for metastasis.

The principal effect of PDT is a selective occlusion of the choriocapillaris layer with relative sparing of photoreceptors and retinal pigment epithelium.26 This mode of action may explain the disappearance in subretinal fluid after PDT as the reduced blood flow in choriocapillaris results in less fluid transudation through the RPE. In our study, subfoveal fluid disappeared completely or decreased considerably in 80% of the eyes with PDT. One study found that PDT does not result in permanent occlusion of vascular channels in CNV but appears to limit the size of CNV and accelerates its involution.27 Therefore, repeated applications may become necessary. PDT applications may cause visual loss due to optic nerve and choroidal ischemic damage.2829

There have been studies on the possible tumoricidal effect of PDT. Mechanisms that have been shown to be involved in the tumoricidal effect of PDT with verteporfin include direct cytotoxicity to tumor cells and selective occlusion of the tumor vasculature, thus starving the tumor of oxygen or nutrients.3031 Because of light absorption characteristics, this effect was found to be more marked in amelanotic choroidal lesions compared to the more pigmented lesions. We found that PDT did not change tumor thickness substantially in the four pigmented and partially pigmented choroidal nevi included in our study. Only one pigmented choroidal nevus shrank down to a flat scar tissue. Therefore, there is no robust evidence relating to the tumoricidal effect of PDT. The use of PDT as a tumoricidal treatment for suspicious choroidal melanocytic lesions to achieve local tumor control similar to transpupillary thermotherapy or plaque radiotherapy can not be recommended at the present time.

In summary, the potential advantage of PDT as a treatment for choroidal nevi close to the fovea is the greater potential for preservation of visual acuity with decrease in subretinal fluid, as supported by the short-term data (minimum 12 months follow-up) in this small series. PDT seems to be a treatment without much harm. However, longer follow-up and a larger number of patients are needed to validate these results.