Kareem Sioufi

VARIABILITY IN FOVEAL AVASCULAR ZONE AND CAPILLARY DENSITY USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY MACHINES IN HEALTHY EYES.

Purpose: To evaluate the variability in foveal avascular zone (FAZ) and capillary density measurements on optical coherence tomography angiography using Optovue RTVue XR Avanti (OA) (Optovue) and Zeiss Cirrus HD-OCT 5000 (ZC) (Carl Zeiss Meditec). Methods: In this prospective, comparative case series, parafoveal (3 × 3 mm) optical coherence tomography angiography scans were obtained on healthy volunteers using both the Avanti and Cirrus. The FAZ area and capillary density at the level of both the superficial and deep capillary plexus were measured automatically using the built-in ReVue software (Optovue) with the Avanti as well as manually using ImageJ (National Institutes of Health) with both machines. Results: There were 50 eyes in 25 healthy volunteers included in the analysis. Mean subject age was 33 years and there were 14 women (56%). On optical coherence tomography, mean central macular thickness was significantly greater on OA (259.1 &mgr;m) than ZC (257.6 &mgr;m, P = 0.0228). On optical coherence tomography angiography, mean superficial and deep plexus FAZ measured 0.2855 mm2 and 0.3465 mm2 on Avanti automated (A-A), 0.2739 mm2 and 0.3637 mm2 on Avanti manual (A-M), and 0.2657 mm2 and 0.3993 mm2 on Cirrus manual (C-M), respectively. There were no statistically significant differences in superficial plexus FAZ measurements between the A-A and A-M (P = 0.4019) or A-A and C-M (P = 0.1336). The A-M measured significantly larger than C-M (P = 0.0396). Deep plexus FAZ measurements were similar on A-A and A-M (P = 0.6299), but both were significantly less compared with C-M (P < 0.0001 for A-A vs. C-M, P = 0.0184 for A-M vs. C-M). Mean superficial and deep plexus capillary densities were 53.6% and 59.3% on A-A, 48.1% and 47.7% on A-M, and 52.5% and 48.1% on C-M, respectively. Superficial plexus capillary density measurements were statistically similar on A-A and C-M (P = 0.0623), but both were significantly higher than A-M (P < 0.0001 for A-A vs. A-M, P < 0.0001 for A-M vs. C-M). However, deep plexus capillary density measurements on A-A were significantly higher than A-M (P < 0.0001) and C-M (P < 0.0001), but A-M and C-M measurements were similar (P = 0.5986). There was no significant difference in all parameters measured in both eyes of one subject using any of the three measuring techniques. Conclusion: While measurements taken with the same machine and technique are consistent and reliable between fellow eyes, significant variability exists in FAZ and capillary density measurements among different machines and techniques. Comparison of measurements across machines and techniques should be considered with caution.

Clinical Features Differentiating Benign From Malignant Conjunctival Tumors in Children

Importance Conjunctival tumors in children are usually benign and rarely malignant. Objective To evaluate clinical features of conjunctival tumors in children by comparing benign tumors with their malignant counterparts. Design, Setting, and Participants This retrospective case series reviewed 806 cases of conjunctival tumor in children (aged <21 years) who were evaluated at a tertiary referral center between November 1, 1975, and July 1, 2015. This study included 262 children who were part of a published review. Main Outcomes and Measures Features of benign and malignant tumors were compared. Data were collected on patient demographics, tumor features, and specific diagnoses to determine findings related to each tumor. Results Among the 806 patients with conjunctival tumor, the top 5 diagnoses included nevus (492 [61%]), benign reactive lymphoid hyperplasia (BRLH) (38 [5%]), nodular conjunctivitis (31 [4%]), dermoid (30 [4%]), and primary acquired melanosis (27 [3%]). Overall, conjunctival tumors were benign (779 [97%]) or malignant (27 [3%]), including melanoma (18 [2.2%]) and lymphoma (9 [1.1%]). The mean age at detection was 11 years for benign tumors and 14 years for malignant tumors (P = .005), with mean difference of 3 years (95% CI, 1.2-4.6). The relative frequency of any malignancy (per all conjunctival tumors) by age bracket (0-5 years, >5-10 years, >10-15 years, and >15-<21 years) was 1%, 2%, 3%, and 7%, respectively. A comparison between nevus and melanoma found differences with melanoma in the 10 to 15 years age bracket (29% vs 61%; difference of 32% [95% CI, 10%-55%]; P = .006), mean tumor thickness (1.1 mm vs 1.5 mm; difference of 0.4 mm [95% CI, −0.29 mm to 1.12 mm]; P = .04), tumor base of 10 mm or greater (relative risk [RR] = 4.92; 95% CI, 1.73-13.97; P = .003), tumor hemorrhage (RR = 25.30; 95% CI, 11.91-53.78; P < .001), and lack of intrinsic cysts (RR = 5.06; 95% CI, 1.84-13.98; P = .002). A comparison between BRLH and lymphoma revealed lymphoma with a larger base (RR = 5.16; 95% CI, 1.19- 22.19; P = .002) and diffuse location (RR = 16.50; 95% CI, 4.31-63.22; P < .001) and inferior (RR = 12.38; 95% CI, 2.88-53.16; P < .001) or superior vs nasal (RR = 8.25; 95% CI, 1.56-43.51; P = .01). The small cohort of malignant lesions precluded determining if these features were independent of one another. Conclusions and Relevance These data, from an ocular tertiary referral center, suggest that conjunctival tumors in children are nearly always benign. The few malignant tumors included melanoma and lymphoma. Melanoma, compared with nevus, was associated with older children (aged >10-15 years) with larger tumor, hemorrhage, and lack of cyst. Lymphoma, compared with BRLH, was associated with larger size and diffuse involvement.

Choroidal nevus: a review of prevalence, features, genetics, risks, and outcomes.

Purpose of review To review the prevalence, clinical features, imaging findings, cytogenetics, and risks and outcomes of choroidal nevus. Recent findings Choroidal nevus is a benign melanocytic tumor, often discovered incidentally on ophthalmic examination. This lesion is generally well circumscribed and pigmented. The prevalence of choroidal nevus in postequatorial region in United States adults (≥40 years old) is approximately 5%. Choroidal nevus is associated with higher lifetime unopposed estrogen and greater BMI. In population-based evaluation, the mean nevus basal dimension is approximately 1.25 mm. Giant nevus (basal dimension ≥10 mm) carries greater risk for malignant transformation. Imaging modalities for evaluation of choroidal nevus include ultrasonography, fundus autofluorescence, and optical coherence tomography (OCT). Fluorescein angiography is occasionally employed to detect multifocal pinpoint leaks or choroidal neovascular membrane. Recently, OCT angiography demonstrated nevus with minimal overlying macular microvascular changes compared with melanoma. Cytogenetically, GNA11 or GNAQ mutations have been documented in uveal melanoma in 83% and in some cutaneous nevus subtypes. Further mutations lead to the development of melanoma at a rate of one of 8845 cases. Risk factors for transformation of nevus into melanoma are recalled by the mnemonic ‘To find small ocular melanoma using helpful hints daily’ representing thickness (T) more than 2 mm, subretinal fluid (F), symptoms (S) of flashes/floaters/blurred vision, orange (O) lipofuscin pigment, margin (M) less than 3 mm from optic disk, ultrasonographic hollowness (UH), halo (H) absence, and drusen (D) absence. The presence of three or more risk factors implies more than 50% chance for transformation to melanoma within 5 years. A new, online ocular oncology reading center can help judge nevus risk. Summary Choroidal nevus is a common intraocular lesion, found predominantly in Whites. This mass carries a small risk (<1%) for malignant transformation. Patients with at least three risk factors should be evaluated for possible melanoma at an experienced ocular oncology center.

Optical coherence tomography angiography of iris microhemangiomatosis

Purpose To report optical coherence tomography angiography (OCTA) of iris microhemangiomatosis. Observations A 75-year-old asymptomatic Caucasian man was found to have bilateral pupillary vascular lesions during cataract evaluation. Visual acuity was counting fingers in the right eye (OD) and 20/40 in the left eye (OS) with normal intraocular pressures in both eyes (OU). In each eye there were multifocal, round, dark red, pinpoint vascular tufts at the pupillary margin, randomly distributed and numbering 1 in OD and 7 in OS, each measuring 0.2–0.3 mm in diameter and without active bleeding or hyphema. Fundus examination OU was normal. By fluorescein angiography, the multifocal pupillary vascular tufts demonstrated mild staining without leakage. By OCTA, the tufts were clearly delineated and were fed by normal appearing radial iris vessels. OCT b-scan documented the optically dense vascular tufts at 0.1 mm in thickness and angio-overlay confirmed blood flow emanating from the deep iris stroma. Observation was recommended with the option of cataract surgery to improve vision. Conclusions and importance Non-invasive imaging of iris microhemangiomatosis with OCTA delineates the vascular lesion with flow arising from the posterior iris stroma.

Uveal Melanoma Associated With Myotonic Dystrophy: A Report of 6 Cases

Importance Patients with myotonic dystrophy (MD) have an increased risk of malignancy including uveal melanoma. This case series further explores the association between these 2 diseases. Objective To describe a cohort of patients with uveal melanoma associated with MD, including a case of iris melanoma, and MD-associated uveal melanoma in relatives. Design, Setting, and Participants Retrospective case series at 3 tertiary referral centers (Wills Eye Hospital, Philadelphia, Pennsylvania; Mayo Clinic, Rochester, Minnesota; and Moorfields Eye Hospital, London, England), between January 1, 2000, and August 31, 2017. The study included 6 patients with MD and uveal melanoma. Main Outcomes and Measures Melanoma response to treatment and development of metastatic disease. Results There were 6 patients, 4 men and 2 women, with MD and uveal melanoma. The mean patient age at melanoma diagnosis was 47 years (median, 43 years; range, 30-67 years), and the tumor involved the choroid in 5 patients (83%) and iris in 1 patient (17%). The diagnosis of MD was known since young adulthood in 2 patients (33%) and was discovered in adulthood in 4 patients (67%). The main clinical features of MD included muscle weakness (n = 5; 83%), myotonia (n = 4; 67%), polychromatic cataract (n = 4; 67%), complications with general anesthesia (n = 4; 67%), myalgia (n = 3; 50%), cardiac arrhythmia (n = 2; 33%), and frontal baldness (n = 2; 33%). Genetic testing revealed MD type 1 (4 of 4 tested patients), and 2 patients demonstrated positive family history of MD with classic clinical features and preferred no testing. Melanoma treatment included plaque radiotherapy (n = 4; 67%), photodynamic therapy (n = 1; 17%), and declined treatment (n = 1; 17%). At follow-up of 6, 6, 41, 42, and 87 months (5 patients), findings included melanoma regression (4 of 5 tumors), melanoma recurrence (1 of 5 tumors), and no metastatic disease (5 of 5 patients). Conclusions and Relevance Six adult patients with MD demonstrated uveal melanoma involving the choroid or iris, emphasizing the association between these 2 diseases. Further research seems warranted to explore the pathogenesis of uveal melanoma in MD. These findings support the consideration of ophthalmic examination for uveal melanoma in patients with MD.

Optical Coherence Tomography Angiography of Conjunctival Racemose Hemangioma

Presented at: American Academy of Ophthalmology 2015; Association for Research in Vision and Ophthalmology 2016. Financial Disclosure(s): Supported by Alimera Sciences Inc., Alpharetta, GA. The funding organization participated in the conduct of the study, and the data collection, data management, and data analysis of this research, and provided financial support for medical writing services by Helios Medical Communications, Alderley Edge, Cheshire, UK. C.W.: Grants e Acucela, Allegro Ophthalmics, Ampio Pharmaceuticals, Apellis Pharmaceuticals, DRCR network/NEI, Iconic Therapeutics, Ophthotech, Pfizer, Santen, pSivida, Tyrogenex, and Xoma; Grants and personal fees e Alcon Laboratories, Inc., Allergan, Clearside Biomedical, Inc., Genentech/Roche, Regeneron Pharmaceuticals, and ThromboGenics, Inc.; Personal fees e Alimera Sciences, Bayer, and DORC International; Personal fees and other e ONL Therapeutics, outside the submitted work. U.C.: Personal fees e Alimera Sciences, during the conduct of the study; Personal fees e Allergan, outside the submitted work. P.C.: Grants and personal feeseAlimera and Allergan during the conduct of the study; Grants e Abbvie, Genzyme, GlaxoSmithKline, and Regeneron; Personal fees e Allegro, Applied Genetic Technologies, Intrexon, and Merck; Grants and personal feeseAerpio, AsclipiX, Genentech/Roche, and Regenexbio; Personal fees and othereGraybug, outside the submitted work. C.B.: Financial support e Alcon, Allergan, Alimera Sciences, Bayer, and Novartis in the form of research funding, grants, research materials, or inkind services. K.G.: Employee and stockholder e Alimera Sciences. J.C.V.: Consultant e Alimera Sciences, Allergan, Bayer, Gene Signal, Novartis, Pfizer, Precision Ocular Ltd., Roche, Sanofi-Aventis, Vifor Pharma, and Carl Zeiss Meditec. Author Contributions: Conception and design: Wykoff, Chakravarthy, Campochiaro, Bailey, Green, Cunha-Vaz Analysis and interpretation: Wykoff, Chakravarthy, Campochiaro, Bailey, Green, Cunha-Vaz Data collection: Wykoff, Chakravarthy, Campochiaro, Bailey, Green, Cunha-Vaz Obtained funding: Not applicable Overall responsibility: Wykoff, Chakravarthy, Campochiaro, Bailey, Green, Cunha-Vaz Abbreviations and Acronyms: DME 1⁄4 diabetic macular edema; DR 1⁄4 diabetic retinopathy; DRCR.net 1⁄4 Diabetic Retinopathy Clinical Research Network; DRSS 1⁄4 diabetic retinopathy severity scale; ETDRS 1⁄4 Early Treatment Diabetic Retinopathy Study; FAc 1⁄4 fluocinolone acetonide; FAME 1⁄4 Fluocinolone Acetonide in Diabetic Macular Edema; IOP 1⁄4 intraocular pressure; NPDR 1⁄4 nonproliferative diabetic retinopathy; PDR 1⁄4 proliferative diabetic retinopathy; PPV 1⁄4 pars plana vitrectomy; PRP 1⁄4 panretinal photocoagulation; VEGF 1⁄4 vascular endothelial growth factor-A. Correspondence: Charles C. Wykoff, MD, PhD, Retina Consultants of Houston, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX 77030. E-mail: ccwmd@houstonretina.com.

Optical Coherence Tomography Angiography Features of Iris Racemose Hemangioma in 4 Cases

Importance Optical coherence tomography angiography (OCTA) allows visualization of iris racemose hemangioma course and its relation to the normal iris microvasculature. Objective To describe OCTA features of iris racemose hemangioma. Design, Setting, and Participants Descriptive, noncomparative case series at a tertiary referral center (Ocular Oncology Service of Wills Eye Hospital). Patients diagnosed with unilateral iris racemose hemangioma were included in the study. Main Outcomes and Measures Features of iris racemose hemangioma on OCTA. Results Four eyes of 4 patients with unilateral iris racemose hemangioma were included in the study. Mean patient age was 50 years, all patients were white, and Snellen visual acuity was 20/20 in each case. All eyes had sectoral iris racemose hemangioma without associated iris or ciliary body solid tumor on clinical examination and ultrasound biomicroscopy. By anterior segment OCT, the racemose hemangioma was partially visualized in all cases. By OCTA, the hemangioma was clearly visualized as a uniform large-caliber vascular tortuous loop with intense flow characteristics superimposed over small-caliber radial iris vessels against a background of low-signal iris stroma. The vascular course on OCTA resembled a light bulb filament (filament sign), arising from the peripheral iris (base of light bulb) and forming a tortuous loop on reaching its peak (midfilament) near the pupil (n = 3) or midzonal iris (n = 1), before returning to the peripheral iris (base of light bulb). Intravenous fluorescein angiography performed in 1 eye depicted the iris hemangioma; however, small-caliber radial iris vessels were more distinct on OCTA than intravenous fluorescein angiography. Conclusions and Relevance Optical coherence tomography angiography is a noninvasive vascular imaging modality that clearly depicts the looping course of iris racemose hemangioma. Optical coherence tomography angiography depicted fine details of radial iris vessels, not distinct on intravenous fluorescein angiography.

Visual Outcome and Millimeter Incremental Risk of Metastasis in 1780 Patients With Small Choroidal Melanoma Managed by Plaque Radiotherapy

Importance Early detection of choroidal melanoma at a small tumor size is emphasized in the literature. However, there is little published information on the specific risks of plaque-irradiated small choroidal melanoma on visual acuity and metastasis. Objective To analyze outcomes of plaque radiotherapy for small choroidal melanoma 3 mm in thickness or less. Design, Setting, and Participants This retrospective noncomparative series at a tertiary referral center included 1780 consecutive patients who had received plaque radiotherapy treatment for small choroidal melanoma. Main Outcomes and Measures Visual acuity outcomes and melanoma-associated metastasis, assessed by Kaplan-Meier analyses. Results The mean (SD) patient age at melanoma diagnosis was 58 (14) years. Of 1780 patients, 908 were female (51.0%), and 1752 were white (98.4%). Visual acuity was 20/40 OU or better in 1276 of the patients (71.7%), and the mean (SD) visual acuity was 20/40 (20/50) OU (median, 20/30; range, 20/20 to counting fingers). The mean (SD) tumor basal dimension was 8.8 (2.9) mm (median, 8.0 mm; range, 2.0-20.0 mm) and mean (SD) tumor thickness was 2.6 (0.5) mm (median, 2.7; range, 0.2-3.4 mm). Mean (SD) distance to the foveola was 3.4 (3.9) mm and to the optic disc was 3.7 (3.7) mm. The Kaplan-Meier rate of visual acuity loss (≥3 Snellen lines) was 9.5% (95% CI, 8.2%-11.0%) at 1 year, 39.2% (95% CI, 36.5%-42.0%) at 5 years, and 48.9% (95% CI, 45.6%-52.3%) at 10 years, whereas poor visual acuity (⩽20/200) was 7.1% (95% CI, 5.9%-8.4%) at 1 year, 38.2% (95% CI, 35.5%-41.1%) at 5 years, and 53.5% (95% CI, 50.1%-57.1%) at 10 years. Regarding melanoma-associated metastasis, the rate was 0.2% (95% CI, 0.09%-0.6%) at 1 year, 4.5% (95% CI, 3.4%-5.9%) at 5 years, and 8.8% (95% CI, 6.9%-11.1%) at 10 years. Using 1.0-mm thickness increments, the 10-year risk for metastasis was 25.0% (95% CI, 3.9%-87.2%) at 0-mm to 1.0-mm thickness, 5.9% (95% CI, 2.5%-13.5%) at 1.1-mm to 2.0-mm thickness, 8.1% (95% CI, 5.9%-11.0%) at 2.1-mm to 3.0-mm thickness, and 13.4% (95% CI, 8.7%-20.4%) at thicknesses greater than 3.0 mm. The greater relative risk (RR) for metastasis in thinnest tumors was 1.83 (95% CI, 1.09-3.07), which likely represented more aggressive diffuse (flat) melanoma. By multivariable analysis, clinical features predictive of melanoma-associated metastasis included increasing patient age (RR, 1.32 [95% CI, 1.07-1.63] per decade; P = .01), tumor diameter (RR, 1.15 [95% CI, 1.06-1.24] per mm; P < .001), tumor thickness (RR, 2.22 [95% CI, 1.22-4.05] per mm; P = .01), photopsia symptoms (RR, 2.45 [95% CI, 1.35-4.43]; P = .003), and prior treatment before plaque radiotherapy (RR, 3.31 [95% CI, 1.31-8.33]; P = .01). Conclusions and Relevance This retrospective study suggests that small choroidal melanoma treated with plaque radiotherapy has a 10-year risk for visual acuity loss of 48.9% (95% CI, 45.6%-52.3%) and a 10-risk of systemic metastasis of 8.8% (95% CI, 6.9%-11.1%). In this analysis, each millimeter of increasing thickness and diameter contributed risk for metastatic disease.

OPTIC NERVE MENINGOCELE SIMULATING EXTRAOCULAR EXTENSION OF CHOROIDAL MELANOMA.

Purpose: To report a case of optic nerve meningocele simulating massive, recurrent extraocular extension of choroidal melanoma. Method: Case report. Results: A 53-year-old white man with choroidal melanoma in his left eye of 7.3-mm thickness was treated with plaque radiotherapy and transpupillary thermotherapy. On 1-year follow-up examination, visual acuity was 20/20 in the right eye and 20/30 in the left eye. The regressed choroidal melanoma scar in the left eye measured 1.5 mm in thickness with stable margins. The optic disk was normal. Ultrasonography demonstrated regressed echogenic choroidal scar, with an echolucent multilobulated retrobulbar mass, suspicious for extraocular extension. On magnetic resonance imaging, the retrobulbar mass corresponded to a distended and kinked optic nerve sheath, filled with extensive subarachnoid fluid and normal-size optic nerve with apposition against the posterior globe. There was no extraocular extension of tumor. Similar but less distended right optic nerve sheath was documented, consistent with optic nerve sheath meningocele in both eyes. Observation was advised and the findings remained stable. Conclusion: Optic nerve sheath meningocele is a benign dilatation of the optic nerve sheath that can simulate orbital tumor or extraocular extension of intraocular tumor. Magnetic resonance imaging can reliably differentiate these conditions.

Caruncular Oncocytoma Mimicking Malignant Melanoma

Purpose: To report a case of pigmented caruncular oncocytoma that simulated malignant melanoma and discuss the associated ultrasonographic and pathologic features. Method: Case report. Results: An 81-year-old female presented with a painless caruncular mass with a smooth brown surface suspicious for melanoma. Ultrasound biomicroscopy revealed a round mass with a large central cavity, more suggestive of a cystic rather than solid lesion. Following complete surgical resection, histopathology revealed a cystadenomatous lesion composed of bland cells with copious eosinophilic cytoplasm consistent with oncocytoma that had a central blood-filled cavity. Conclusions: Oncocytoma is a benign tumor that can appear pigmented clinically and resemble melanoma. The definitive diagnosis requires histopathologic evaluation. Oncocytoma should be considered in the differential diagnosis of a pigmented caruncular mass.