Patient notices changes inferiorly in left eye

Jeffrey Chang

Vivek Chaturvedi

An 80-year-old man presented to the Lahey Clinic Eye Institute for routine eye examination for Plaquenil use without a history of maculopathy. The patient said his vision had been stable in general, but he noted some changes inferiorly in his left eye when viewing the Amsler grid. He denied any other associated symptoms and reported the presence of chronic floaters without flashing lights.

His ocular history was significant for distant cataract surgery in both eyes and a choroidal nevus and mild epiretinal membrane in the left eye. His medical history was notable for rheumatoid arthritis managed on Plaquenil (hydroxychloroquine, Sanofi-Aventis), prostate cancer without metastasis treated with radioactive seed placement, and coronary artery disease with past myocardial infarction managed with stenting. He had no significant family history of eye disease, denied alcohol or tobacco use, and had a negative review of systems. In addition to Plaquenil, his medications included Zocor (simvastatin, Merck), Lipitor (atorvastatin, Pfizer) and Ecotrin (aspirin, GlaxoSmithKline).

Examination

On examination, the patient’s best corrected visual acuity was 20/20 in both eyes with normal pupillary responses without relative afferent defect. Amsler grid evaluation was significant for wavy lines inferior to fixation in the left eye. The remainder of his testing was within normal limits in both eyes – full confrontational visual fields, full color identification with Ishihara plates and ocular tensions of 16 mm Hg bilaterally. The anterior segments of both eyes were normal and quiet with posterior chamber IOLs noted bilaterally.

The posterior examination (Figure 1) showed clear media, healthy optic nerve heads and normal vasculature. Examination of the left fundus showed a flat, slightly hyperpigmented lesion in the parafoveal region with overriding subretinal fluid, subretinal hemorrhage and a grayish-green discoloration.

Figure 1. Posterior examination showed clear media, healthy optic nerve heads and normal vasculature. Images: Lazzara M, Marx J

What is your diagnosis?

Hyperpigmented lesion

Our patient had a fluorescein angiogram and optical coherence tomography performed (Figure 2). The fluorescein angiogram demonstrated early lacy hyperfluorescence and prominent leakage on later phases. On OCT, a fragmented RPE-choriocapillaris band was seen with edematous overlying retina and minimal subretinal fluid. Given these findings, our patient was determined to have choroidal nevus-associated choroidal neovascularization.

Discussion

Choroidal nevi are a common finding on funduscopic examination, with an incidence near 6.5% in people over the age of 49 years and 20% in people of the same age group on autopsy studies. With such a high encounter rate in ophthalmic patients being seen for generally unrelated issues, it is important to quickly recognize the clinical characteristics that preclude a further diagnostic work-up.

Concomitantly, these generally benign choroidal nevi should also be evaluated for their role influencing vision. The obvious important rule-out diagnosis of pigmented lesions being choroidal melanoma, other lesions such as choroidal metastasis, subretinal or choroidal hemorrhage, congenital hypertrophy of the retinal pigment epithelium, age-related macular degeneration, melanocytoma of the optic nerve and retinal pigment epithelial tumors also need to be excluded. While amelanotic nevi are less common, found in 6% to 10% of cases, they complicate diagnostic matters and share a differential with amelanotic melanoma, choroidal metastasis, choroidal hemangioma, choroidal granuloma, choroidal osteoma, posterior scleritis and sclerochoroidal calcification.

Atypical melanocytes, which make up these benign uveal tumors, are categorized based on histopathology and include spindle nevus cells, magnocellular nevus cells, epithelioid nevus cells and balloon nevus cells. Epithelioid cells are considered the most prone to malignant transformation and are the predominant type observed in choroidal melanoma pathology sections. Gass theorized that nevi begin as small cell nests that then become hyperplastic usually, but not exclusively, in late childhood and early adulthood secondary to underlying hormonal changes. This implies a period of growth in lesions that could and likely would be observed in ultimately benign lesions. The incidence of observed benign growth of melanotic lesions is low – 3% to 4 % in a study of 3,422 eyes with choroidal nevi at a tertiary referral center, and only in one of 160 lesions in a population-based study.

Figure 2. Fluorescein angiogram demonstrated early lacy hyperfluorescence and prominent leakage on later phases. OCT showed a fragmented RPE-choriocapillaris band with edematous overlying retina and minimal subretinal fluid.

Lack of confidence in diagnosis has historically led to unwarranted enucleation and continues to result in high rates of referral to oncology centers. Khand and Damato found a 30% false positive rate among patients referred to ocular oncology centers from primary ophthalmologists in a review published in 2007.

The risk for choroidal nevi malignant transformation is approximately one in 5,000 lesions. Factors for conversion include thickness greater than 2 mm, subretinal fluid, the presence of symptoms, prominent orange lipofuscin pigment over the lesion and a location less than 3 mm from the optic disc. In addition, lack of overlying drusen, fluorescein angiographic hot spots and hollowness on ultrasonography are worrisome findings. Drusen on top of choroidal nevi, although subtle, were found in 98% of high-resolution photos of cases and are felt to imply chronicity and stagnation of the lesion. Angiography is helpful, as it can occasionally highlight large choroidal intralesional vessels associated with melanomas. The use of ultrasound allows the depth of the lesion to be accurately assessed, and an evaluation for scleral invasion can be made. In addition, choroidal nevi show high internal reflectivity throughout while a heterogenous, low-intensity signal often is caused by the abnormal vasculature and dysplasia of a melanoma.

Choroidal nevi are most commonly found between the macula and equator and are pigmented nearly 80% of the time. A subfoveal location is associated with a much higher rate of visual symptoms (26% vs. 2%). Symptoms include visual acuity loss, metamorphopsia, visual field defects, and flashes and floaters. These changes are induced by chronic nutritional and anatomical disruption to the choriocapillaris, Bruch’s membrane and the retinal pigment epithelium. Clinically they appear as cystic degeneration of the retina, subretinal fluid, subretinal hemorrhage and/or choroidal neovascularization.

The incidence of CNV with choroidal nevi in community studies has not been defined; however, even in studies at tertiary referral centers, the rate appears to be low. Gonder found only two cases in 206 patients with choroidal nevi referred to Wills Eye Hospital, and CNV was found to be the cause of visual changes in just 8% of those with any symptomatic effects. Both Gass and Waltman felt the occurrence of CNV was an indicator of chronicity rather than malignant transformation. Callanan and others observed 23 patients with choroidal nevi-associated CNV and found only a single case of lesion growth, and that was after 17 years of no growth. Regarding visual acuity, patients often did well in this study, with three patients having no change in central vision, 14 patients showing a change in vision of two lines or less, and seven patients having a decrease of vision of two lines or less.

Treatment

Treatment options for CNV associated with choroidal nevi include laser photocoagulation, photodynamic therapy with verteporfin, transpupillary thermotherapy and anti-VEGF therapy. The best option obviously takes into consideration the location of the CNV, whether found subfoveal, juxtafoveal or extrafoveal. No large studies have been completed evaluating treatment of subfoveal choroidal nevi-related CNV, but case reports have shown success with both PDT and transpupillary thermotherapy. While several case reports have been published regarding CNV and choroidal osteoma, to our knowledge, no studies have been done to evaluate the role of anti-VEGF treatment in choroidal nevi-related CNV. However, given the efficacy of these medications in treatment of CNV in general, it is presumed that this is a successful and commonly used primary and adjuvant therapy to the aforementioned.

Given the presence of the CNV membrane and proximity to the fovea, our patient was treated with both PDT and Lucentis (ranibizumab, Genentech). At 4 months, the CNV had regressed slightly and his visual acuity remained unchanged. He will be observed closely and likely re-treated to prevent further damage and extension.

References:

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• Matthew Lazzara, MD, and Jeffery Marx, MD, can be reached at Tufts Medical Center, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.

• Edited by Jeffrey Chang, MD, and Vivek Chaturvedi, MD. Drs. Chang and Chaturvedi can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.