Molecular profiling of renal cell carcinoma presenting as iris metastasis.

Purpose: To describe a case of iris metastasis as the initial presentation of clear cell renal cell carcinoma, and to discuss molecular profiling of both the metastasis and primary kidney tumor. Observations: We report a patient with blurred vision who underwent ophthalmic examination and was found to have an iris mass, which was excised and diagnosed as a metastatic clear cell renal cell carcinoma by morphology and immunohistochemical analysis. As a result of the pathology findings, computed tomography imaging was performed, revealing a right kidney mass, which was also resected and shown to represent a high-grade carcinoma confined within the renal fascia without lymphovascular invasion. Molecular testing of the primary and metastatic tumors using a custom next-generation sequencing panel revealed similar mutational profiles but disclosed a TERT promoter mutation in the primary neoplasm, not present in the metastasis, suggesting seeding of an early lower grade neoplastic cell clone within the iris. Conclusions and importance: This report illustrates how pathological examination of a small iris lesion led to the discovery of a previously unknown systemic malignancy at a resectable stage. Molecular genetic profiling revealed that even lower grade clones within a high-grade neoplasm have metastatic potential.

Clinical and histopathologic findings after photodynamic therapy of choroidal melanoma.

BACKGROUND: Photodynamic therapy (PDT) has been used occasionally as an alternative treatment for uveal melanomas. The present study describes the clinical and histopathologic features of five choroidal melanomas after PDT. METHODS: Three patients with pigmented choroidal melanomas were treated with PDT and intravitreal bevacizumab 1 week before undergoing biopsy and brachytherapy to minimize the risks of bleeding during the biopsy. Another two patients received PDT as a primary treatment for peripapillary amelanotic melanomas, one of them also in combination with bevacizumab. RESULTS: The tumors treated with PDT and bevacizumab showed a marked reduction in tumor vascularity assessed by indocyanine angiography, and the biopsies were conducted without recognizable bleeding, showing viable tumor cells. The tumors receiving PDT as a primary treatment were followed by progressive tumor growth that led to enucleation years after. The histopathology revealed overlying fibrosis with invasion of sclera and optic nerve. CONCLUSION: Photodynamic therapy and bevacizumab can induce closure of the superficial vasculature of a pigmented choroidal melanoma, but in none of our cases, there was evidence of tumor destruction from this treatment. Preoperative PDT may be useful to reduce the potential of bleeding at the time of tumor biopsy. Our cases do not support the use of a single session of PDT as a primary treatment for pigmented small choroidal melanomas.

Histopathologically proven mucinous cystadenocarcinoma metastatic to the choroid.

PURPOSE: To report the first case of conventional transcleral choroidal biopsy in the diagnosis of ovarian carcinoma metastatic to the choroid and to summarize the published cases of ovarian carcinoma metastatic to the choroid. METHODS: Case report and Medline literature review. RESULTS: This is the tenth case reported in the literature and the only case that underwent conventional transcleral choroidal biopsy. Transcleral choroidal biopsy allowed the diagnosis of metastatic mucinous cystadenocarcinoma of the ovary. Choroidal metastases are not associated with central nervous system involvement; however, investigations may reveal distal boney or pulmonary metastases. CONCLUSION: Ovarian carcinoma rarely metastases to the choroid and unlike breast carcinoma, concurrent central nervous system disease has not been reported. When systemic investigations fail to reveal active intraperitoneal disease or distal metastases, the clinician should consider referral to an ocular oncology center for a choroidal biopsy.

Anterior ciliary circulation from the horizontal rectus muscles.

PURPOSE: To quantify the anterior ciliary arteries that accompany horizontal rectus muscles and to correlate these findings with analysis of arterial cross-sectional area in distal tendons of these muscles. PATIENTS AND METHODS: In 31 consecutive patients, previously unoperated horizontal rectus muscles were photographed intraoperatively. Major and minor anterior ciliary arteries (ACAs) were counted from the photographs by a masked independent observer and compared between medial and lateral rectus muscles. Cross sections from medial and lateral rectus muscle resection specimens were stained for elastin to quantify arterial volume in the distal tendons. RESULTS: Twenty lateral and 22 medial rectus muscles from 31 patients were included. There was no significant difference in the mean number of major anterior ciliary arteries between lateral rectus muscles (2.25 +/- 0.79, range 1-4) and medial rectus muscles (2.05 +/- 0.65, range 1-3) (p = 0.46). The mean number of minor anterior ciliary arteries was 6.7 in both medial and lateral rectus muscles (p = 0.97). Resected rectus muscle tendons showed no significant difference between lateral and medial rectus muscles for arterial vessel number or cross-sectional area. CONCLUSIONS: These results show the contribution from the lateral rectus muscle to the anterior segment circulation may be more robust than is commonly taught.

Improvement in visual fields in a patient with melanoma-associated retinopathy treated with intravenous immunoglobulin.

Melanoma-associated retinopathy (MAR) is a rare disorder characterized by photopsias, shimmering vision, nyctalopia, and dysfunction of rod photoreceptor cells. We describe a 56-year-old man with metastatic cutaneous melanoma to the lymph nodes and MAR. He underwent resection of the metastasis followed by radiation therapy. Over the ensuing 2 months, visual function worsened so he was treated with intravenous immunoglobulin (IVIg). Visual fields, but not electroretinography, improved steadily over the next year. No evidence of recurrence or metastatic disease has been found. Our patient indicates that even after a reduction or elimination of melanoma tumor burden and presumably the attenuation of the antigenic stimulus driving MAR, this disorder can continue to progress. In this setting, IVIg therapy should be considered a viable treatment option.

Macular dystrophy associated with the A3243G mitochondrial DNA mutation. Distinct retinal and associated features, disease variability, and characterization of asymptomatic family members.

OBJECTIVES: To determine (1) detailed retinal and audiological features of probands harboring the A3243G mitochondrial DNA mutation (m.3243A>G) and their asymptomatic maternal relatives, (2) intrafamilial and interfamilial phenotypic variability, and (3) the presence of other systemic features. METHODS: Seven probands harboring the A3243G mitochondrial DNA mutation and 36 asymptomatic maternal relatives were ascertained. Participants underwent ophthalmologic examination, fundus photography, autofluorescence imaging, and audiological evaluation and completed a questionnaire. Blood samples were taken to test for diabetes, determine renal function, and screen relatives for the A3243G mutation. RESULTS: The A3243G mutation was associated with both intrafamilial and interfamilial variable expressivity regarding retinal appearance, hearing loss, diabetes, and other systemic features. The most common macular appearance in maternal relatives (one-third of those positive for the mutation) was mild abnormalities of the retinal pigment epithelium (more clearly identified using autofluorescence), which may therefore be a useful clinical indicator suggesting positive mutation status. Four probands and 13 mutation-positive relatives were found to have evidence of significant bilateral, cochlear, symmetrical age-adjusted hearing loss, predominantly affecting high frequencies. CONCLUSIONS: Hearing loss and macular disturbance were the most frequent findings in mutation-positive participants, with 95% of mutation-positive relatives having hearing loss. Diabetes was the least frequent finding. Patients with progressive hearing loss may merit ophthalmologic assessment to detect retinal abnormalities consistent with the A3243G mutation. Conversely, patients with macular features in keeping with the A3243G mutation should have audiological testing, even in the absence of diabetes or a positive family history.

Localized retinal electrophysiological and fundus autofluorescence imaging abnormalities in maternal inherited diabetes and deafness.

PURPOSE: To investigate retinal function in patients with maternally inherited diabetes and deafness (MIDD) and to correlate the findings with fundus autofluorescence (FAF) imaging. METHODS: FAF was imaged in five patients (age range, 49-60 years) confirmed to have the mitochondrial DNA nucleotide A3243G point mutation. Retinal function was measured by full-field (Ganzfeld) electroretinography (ERG) and pattern ERG, incorporating the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Multifocal ERG (mfERG) was also performed. For analysis of the mfERG data, five regional ring groups of equal eccentricity were formed. For each ring, the peak amplitude (defined as the difference between P1 and N1) and the implicit time of P1 were determined and compared with normative values. RESULTS: Visual acuity in the patients was between 20/20 and 20/40 (Early Treatment Diabetic Retinopathy Study [ETDRS] chart). Irregular increased FAF signals were observed adjacent to and between areas of atrophy of the retinal pigment epithelium (RPE). Ganzfeld ERGs were within normal limits in three patients. Pattern ERG was abnormal in five eyes of three patients. mfERG peak amplitude abnormalities were particularly present in rings 2 and 3 and were consistent with the distribution of FAF abnormalities. In all but one eye, no implicit times changes were present. CONCLUSIONS: Significant mfERG abnormalities with normal Ganzfeld ERG are consistent with nonuniform damage to the central retina in MIDD, in keeping with the FAF findings. Reduced peak amplitudes with normal implicit times in the mfERG suggest localized loss of function and may indicate damage to the cone photoreceptor outer segments or cone photoreceptor loss in MIDD.

Fluorescein angiographic lesion type frequency in neovascular age-related macular degeneration.

OBJECTIVE: To assess the frequency of lesion types using fluorescein angiography (FA) in neovascular age-related macular degeneration (nAMD). DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred cases of nAMD. METHODS: Fluorescein angiograms from 908 patients (university-based, tertiary retinal referral practice [UP] = 478; comprehensive, community-based eye clinic [CC] = 430) were reviewed to identify 200 cases of nAMD (100 from each center). Two graders evaluated the frequency of angiographic subtypes. MAIN OUTCOME MEASURES: Identifying (1) the frequency of subfoveal nAMD lesions that meet the definition of "predominantly classic," "minimally classic," "occult with no classic"; (2) lesion location, size, and subtype; and (3) the intergrader agreement (kappa). RESULTS: There was little difference in the frequency of lesion type between the UP and the CC. Most nAMD lesions were subfoveal (78.5%, 157 of 200), and of these, 20% (32 of 157) were predominantly classic; whereas 73% (114 of 157) were occult with no classic, and 7% (11 of 157) were minimally classic. Of the 200 angiograms, 33 (16.5%) were juxtafoveal, and 10 (5%) were extrafoveal. Twenty of the 43 juxtafoveal and extrafoveal lesions (47%) were predominantly classic. Classic with no occult subfoveal lesions were smaller than minimally classic or occult with no classic (1.7 vs. 3.7 and 2.8 mm; P = 0.001 and 0.01, respectively). Of 114 subfoveal occult with no classic lesions, 54 (47%) had both smaller lesion size <==4 disc areas (DA) and lower visual acuity <20/50, whereas 107 (94%) had a smaller lesion or lower visual acuity. CONCLUSIONS: Most angiographic lesions of patients who undergo FA for nAMD are subfoveal and occult. We estimate that 20% of subfoveal lesions are predominantly classic. Approximately half of the juxtafoveal and extrafoveal lesions are predominantly classic. Nearly 30% of all nAMD lesions have both small occult lesions (size <==4 DA) and a visual acuity less than 20/50. We found minimal difference in lesion type between a UP and a CC.