Faculty Bibliography

OBJECTIVE: To collaborate with multiple centers to identify representative epidemiological, clinical, and pathologic characteristics of melanoma of the iris. This international, multicenter, Internet-assisted study in ophthalmic oncology demonstrates the collaboration among eye cancer specialists to stage and describe the clinical and pathologic characteristics of biopsy-proven melanoma of the iris. METHODS: A computer program was created to allow for Internet-assisted multicenter, privacy-protected, online data entry. Eight eye cancer centers in 6 countries performed retrospective chart reviews. Statistical analysis included patient and tumor characteristics, ocular and angle abnormalities, management, histopathology, and outcomes. RESULTS: A total of 131 patients with iris melanoma (mean age, 64 years [range, 20-100 years]) were found to have blue-gray (62.2%), green-hazel (29.1%), or brown (8.7%) irides. Iris melanoma color was brown (65.6%), amelanotic (9.9%), and multicolored (6.9%). A mean of 2.5 clock hours of iris was visibly involved with melanoma, typically centered at the 6-o'clock meridian. Presentations included iritis, glaucoma, hyphema, and sector cataract. High-frequency ultrasonography revealed a largest mean tumor diameter of 4.9 mm, a mean maximum tumor thickness of 1.9 mm, angle blunting (52%), iris root disinsertion (9%), and posterior iris pigment epithelium displacement (9%). Using the American Joint Commission on Cancer-International Union Against Cancer classification, we identified 56% of tumors as T1, 34% of tumors as T2, 2% of tumors as T3, and 1% of tumors as T4. Histopathologic grades were G1-spindle (54%), G2-mixed (28%), G3-epithelioid (5%), and undetermined (13%) cell types. Primary treatment involved radiation (26%) and surgery (64%). Kaplan-Meier analysis found a 10.7% risk of metastatic melanoma at 5 years. CONCLUSIONS: Iris melanomas were most likely to be brown and found in the inferior quadrants of patients with light irides. Typically small and unifocal, melanomas are commonly associated with angle blunting and spindle cell histopathology. This multicenter, Internet-based, international study successfully pooled data and extracted information on biopsy-proven melanoma of the iris

PURPOSE: To report the results and complications of an aspiration cutter-assisted anterior segment tumor biopsy performed under viscoelastic. DESIGN: Retrospective, consecutive, interventional case series. METHODS: Fifty-five patients with anterior segment tumors underwent aspiration cutter-assisted biopsy at a single center. Fifty-six biopsies were performed, because 1 eye underwent biopsy twice. Indications for biopsy included: suspected anterior segment malignancy, patient's desire for pathologic confirmation before treatment, atypical tumor, and genetic tumor analysis. The main evaluated outcomes were the perioperative visual acuity, the biopsy technique, and related complications. RESULTS: The initial sample comprised 55 consecutively biopsied patients, from which a minimum 1-month follow-up existed for 52 biopsy samples. The median total follow-up was 30.4 months (range, 1 to 190 months). The mean initial visual acuity was 20/50 before and 20/50 1 month after biopsy. No patient lost vision. Most cases were suspected iris melanoma (n = 39/56; 69.6%), followed by suspicious iris nevi (n = 4/56; 7.1%) and melanocytoma (n = 4/56; 7.1%). Seven (n = 7/52; 13.4%) wounds required a single 10-0 nylon suture to achieve negative Seidel test results at the corneal entry site. Postoperative surgical findings included transiently increased intraocular pressure (n = 6/52; 11.5%), 1 hyphema, 1 flare, and 1 persistent pupillary defect. All but the pupillary defect resolved within 4 weeks of the biopsy procedure. There were no secondary infections or cataracts. CONCLUSIONS: This study suggests that small-incision, aspiration cutter-assisted anterior segment biopsy seems to be a safe and effective procedure. No short- or long-term complications that would prevent its use were noted

Purpose. To evaluate the safety and effect of systemic anti-vascular endothelial growth factor bevacizumab (Avastin) in treatment of exudative retinal detachment secondary to choroidal melanoma. Methods. Two patients were definitively treated with ophthalmic plaque radiation therapy and subsequently given 10 mg/kg intravenous bevacizumab every 2 weeks for 3 or 4 cycles. Results. Complete resolution of the exudative retinal detachments occurred 1.2 months and 6.5 months after completion of systemic bevacizumab and 4.7 and 10 months after plaque therapy. The first patient's visual acuity improved from counting fingers at 1 foot to 20/80 (at 40 months), while his tumor regressed from 9.2 to 3.7 mm in apical height. The second patient's initial acuity was 20/20 and final acuity was 20/80 (at 35 months), while her tumor height regressed from 12.2 to 6.3 mm. No exudative retinal detachment, intraocular or systemic tumor recurrence was noted up to 40 and 35 months, respectively. Acute side effects of intravenous bevacizumab therapy included hypertension, headaches, and amenorrhea, which shortly resolved after completion of therapy. Conclusions. This pilot study suggests that systemic bevacizumab was associated with transient systemic effects as well as resolution of choroidal melanoma-related exudative retinal detachment

PURPOSE: To present an interventional case report on the use of plaque brachytherapy for adenocarcinoma of the nonpigmented ciliary epithelium. METHODS AND MATERIALS: A 36-year-old woman with unilateral right eye pain and finger counting vision was noted to have an anterior segment intraocular mass. It extended between the iris and lens and into the pupillary aperture. High-frequency ultrasound imaging revealed a ciliary body origin. A minimally invasive biopsy technique allowed for a cytology and histopathology diagnosis of primary adenocarcinoma of the ciliary epithelium. Treatment was performed with palladium-103 ophthalmic plaque brachytherapy (80-Gy apex). Main outcome measures include visual acuity, local control, radiation complications, and metastatic disease. RESULTS: The patient presented with counting fingers vision, focal angle closure, cataract, and a 5.5-mm thick ciliary body malignancy. At 3 years after radiation therapy and 2.5 years after cataract extraction, her visual acuity was improved to 20/30 and the tumor residua stabilized at 60% of its initial thickness. There has been neither radiation-related keratopathy, retinopathy, optic neuropathy nor metastatic disease. CONCLUSIONS: Plaque brachytherapy was used to treat primary adenocarcinoma of the ciliary epithelium. With 3-year followup, there has been excellent local control, preservation of the eye, and recovery of vision

PURPOSE: To report pathologic evaluation and diagnostic yield of an aspiration cutter-assisted biopsy of anterior segment tumors. DESIGN: Retrospective, consecutive, interventional case series. METHODS: Fifty-five eyes of 55 patients with iris and iridociliary tumors underwent an aspiration cutter-assisted biopsy at a single institution. Cytospin and cell-block preparations were performed on all biopsy samples. Bleached preparations and a panel of immunohistochemical stains were performed in selected cases. Cytologic diagnosis was correlated with clinical diagnosis and with histopathologic diagnosis, when available. Main outcome measures were (1) specimen cellularity, (2) diagnostic studies performed, (3) cytopathologic diagnosis, and (4) concordance with histopathologic diagnosis. RESULTS: Specimen cellularity was adequate for cytopathologic interpretation of cytospin preparations in 55 (98.2%) of 56 biopsies. Twenty-three (41%) of 56 biopsy samples had diagnostic material in cell-block preparations. The most common cytopathologic diagnoses were melanoma (n = 39/56; 69.6%), melanocytoma (n = 4/56; 7.1%), nevus (n = 4/56; 7.1%), lymphoma (n = 2/56; 3.6%), and epithelial implantation cyst (n = 2/56; 3.6%). One biopsy sample (1.8%) yielded nondiagnostic material. Wide incisional or excisional biopsy confirmation was available in 13 (23.2%) of 56 aspiration cutter-assisted biopsy cases. Cytopathologic diagnoses were consistent with histopathologic diagnosis in 12 (92.3%) of 13 cases. CONCLUSIONS: Although specialized pathologic techniques were necessary to maximize material available for diagnosis, all biopsies yielded cellular material and 41% yielded diagnostic tissue in cell block preparation. Although lower than the yield of wide incisional or excisional biopsy, aspiration cutter-assisted biopsy of anterior segment tumors achieved a diagnostic yield of 98.2%

OBJECTIVE: To evaluate a case series of anterior uveal melanocytomas (AUMs) for their distinct clinical, histopathologic, and high-frequency ultrasound (UBM) characteristics. DESIGN: Retrospective single-center case series. PARTICIPANTS: Seventeen consecutive patients with AUMs. METHODS: Retrospective review of patient, tumor, UBM, histopathologic, and follow-up characteristics. Follow-up data included change in visual acuity, growth, secondary glaucoma, extrascleral extension, or malignant transformation. MAIN OUTCOME MEASURES: Tumor, high-frequency ultrasound, histopathologic, and follow-up characteristics. RESULTS: Seventeen patients had a median follow-up of 20 months (range, 1-130). Tumor was darkly pigmented with nodular configuration in 100% of patients, irregular surface in 82% of patients, characteristic cobblestone surface appearance in 59% of patients, and feathery or fimbriated margins in 88% of patients. Intrinsic vascularity, ectropion uveae, episcleral sentinel vessel, sector cataract, or heterochromia was not seen. High-frequency ultrasound showed high (71%) or moderately high (12%) internal reflectivity in the majority of tumors. Thirteen tumors (76%) involved the iris, 47% of tumors were club-shaped, and 100% of tumors showed no intrinsic vascularity. Mean tumor thickness was 1 mm (standard deviation [SD] +/- 0.5, median 0.9, range 0.3-2.1 mm). Mean largest basal dimension was 3.1 mm (SD +/- 2.3, median 2.3, range 0.5-9.4 mm) (n=14). Three pathologic evaluations revealed plump polyhedral cells with abundant cytoplasm, small round to oval nuclei, inconspicuous nucleoli, and finely dispersed chromatin. Two tumors had extrascleral extension, 2 tumors were documented to grow, and 1 tumor caused medically controlled glaucoma. CONCLUSIONS: Anterior uveal melanocytomas are uncommon benign melanocytic tumors with characteristic clinical features. High-frequency ultrasound imaging offers excellent views of obscure posterior extent and allows precise tumor measurement and monitoring for growth. It is an invaluable adjunct to digital slit-lamp photography for evaluating tumor stability or growth. This study presents and correlates unique clinical, high-frequency ultrasound and histopathologic characteristics. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article

Purpose: To report an immunocompetent patient with Nocardia exalbida endogenous endophthalmitis. Design: Case report. Methods: Clinical-pathologic correlation and microbiologic evaluation were performed on an enucleated eye. Results: A 56-year-old man presented with rapidly progressive vision loss associated with a posterior choroidal mass and serous retinal detachment. Pathologic evaluation of the enucleated eye demonstrated endogenous endophthalmitis. Nocardia exalbida was identified microbiologically. Systemic workup failed to demonstrate definite foci of systemic infection or evidence of immunocompromise. Review of literature failed to identify previously reported cases of Nocardia exalbida endophthalmitis. Conclusions: Nocardia can rarely cause isolated endogenous endophthalmitis in immunocompetent patients, which can contribute to a delay in diagnosis and vision loss

PURPOSE: To examine how tumor characteristics and dose affect cataract development after plaque radiation therapy. METHODS AND MATERIALS: Three hundred and eighty-four patients were diagnosed with uveal melanoma and treated with palladium-103 ((103)Pd) plaque radiation therapy. Of these, 282 (74%) inclusion met exclusion criteria for follow-up time, tumor location, and phakic status. Then patient-, ophthalmic-, and radiation-specific factors (patient age, diabetes, hypertension, tumor location, tumor dimensions, and lens dose) were examined (by a Cox proportional regression model) as predictors for the development of radiation-related cataract. RESULTS: Radiation cataract developed in 76 (24%) of patients at a mean follow-up of 39.8 months (range, 1-192). Patients with anteriorly located tumors were noted to have a higher incidence of cataract at 43.0% (43 of 100 patients) vs. 18.1% (33 cataracts per 182 patients) for posteriorly located tumors (p <0.0001). However, multivariate Cox proportional modeling showed that increasing patient age at time of treatment (p for trend = 0.0003) and higher lens dose (p for trend = 0.001) were the best predictors (biomarkers) for radiation cataract. CONCLUSIONS: Although anterior tumor location, greater tumor height, and increased patient age (at treatment) were associated with significantly greater risk for radiation cataract, dose to lens was the most significant factor

OBJECTIVE: To evaluate the clinical presentation, tumor characteristics, and response to palladium 103 plaque radiation therapy for subfoveal choroidal melanomas. METHODS: Retrospective case series of 50 patients diagnosed as having subfoveal melanoma and treated with plaque brachytherapy. Patients underwent evaluation for tumor characteristics, visual acuity, radiation damage, local tumor control, and metastatic disease. RESULTS: Patients were followed up for a median of 54 (SD, 49.3) months. Forty-nine tumors (98%) were dome shaped. Subretinal fluid (overlying or a dependent exudative retinal detachment) was evident in 34 of 45 patients (76%). Treatment involved an apical radiation dose of 82.8 Gy (delivered across 5-7 days), resulting in a mean dose of 157.7 Gy to the fovea. Pretreatment median visual acuity was 20/50, which declined to 20/180 at last follow-up. Visual acuity was better than 20/200 in 33 patients (66%) at baseline and 25 (50%) at last follow-up; 13 patients (26%) lost 6 or more lines of vision. Twenty-eight patients (56%) developed radiation retinopathy; 16 (32%) required secondary intervention for radiation retinopathy, including intravitreal antivascular endothelial growth factor therapy, laser treatment, cryotherapy, or pars plana vitrectomy. The local tumor control rate of subfoveal tumors was 92%. Four patients (8%) required secondary enucleation. Metastasis developed in 2 patients (4%). CONCLUSIONS: Subfoveal choroidal melanomas in this series are almost exclusively dome shaped and likely to have an associated exudative retinal detachment. They are amenable to plaque radiation therapy. However, this tumor location is associated with a high incidence of radiation maculopathy and a low incidence of radiation cataract

BACKGROUND AND OBJECTIVE: To determine the normal ultrasonographic thickness of the iris and ciliary body. PATIENTS AND METHODS: This prospective 35-MHz ultrasonographic study included 80 normal eyes of 40 healthy volunteers. The images were obtained at the 12-, 3-, 6-, and 9-o'clock radial meridians, measured at three locations along the radial length of the iris and at the thickest section of the ciliary body. Mixed model was used to estimate eye site-adjusted means and standard errors and to test the statistical difference of adjusted results. Parameters included mean thickness, standard deviation, and range. RESULTS: Mean thicknesses at the iris root, midway along the radial length of the iris, and at the juxtapupillary margin were 0.4 +/- 0.1, 0.5 +/- 0.1, and 0.6 +/- 0.1 mm, respectively. Those of the ciliary body, ciliary processes, and ciliary body + ciliary processes were 0.7 +/- 0.1, 0.6 +/- 0.1, and 1.3 +/- 0.2 mm, respectively. CONCLUSION: This study provides standard, normative thickness data for the iris and ciliary body in healthy adults using ultrasonographic imaging