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Purpose To report the efficacy of photodynamic therapy (PDT) for management of retinal hemangioblastoma. Design Retrospective case series. Participants Seventeen patients with retinal hemangioblastoma treated with PDT. Methods The medical records of 17 patients with retinal hemangioblastoma treated with PDT were reviewed, and treatment outcomes were assessed. Photodynamic therapy was performed with 6 mg/m2 body surface area of verteporfin infused intravenously over 10 minutes activated by 50 J/cm2 laser light at 689 nm for 83 or 166 seconds. Main Outcome Measures Tumor control, subretinal and intraretinal fluid resolution, and visual outcome. Results Eighteen retinal hemangioblastomas in 17 eyes were treated with PDT. Median patient age was 31 years (mean, 36 years; range, 7–66 years), and median follow-up was 51 months (mean, 61 months; range, 2–144 months). Genetic testing confirmed von Hippel-Lindau disease in 8 of 17 patients (47%). The tumors were unilateral in all patients and unifocal in most patients (n = 13/17 [76%]). The tumor median basal diameter was 3.5 mm (mean, 3.4 mm; range, 1.5–6.0 mm) and median thickness was 2.1 mm (mean, 2.3 mm; range, 1.0–5.0 mm). The tumor location was juxtapapillary in 9 of 18 cases (50%). Associated findings included subretinal fluid (n = 14/17 [82%]) and macular edema (n = 12/17 [71%]). The median number of PDT sessions was 1.5 (mean, 1.8; range, 1.0–4.0). Standard duration of PDT (83 seconds) was used in all cases except 2, in which double duration (166 seconds) was used. Outcomes revealed tumor control in 13 of 18 tumors (72%), partial or complete resolution of subretinal fluid in 10 of 14 eyes (71%), and partial or complete resolution of macular edema in 7 of 12 eyes (58%), and stable or improved visual acuity in 12 of 17 eyes (71%). Photodynamic therapy-related transient exudative response was noted in 4 of 17 eyes (24%). Conclusions Photodynamic therapy is an effective treatment for both juxtapapillary and peripheral retinal hemangioblastomas, providing satisfactory rates of tumor control and visual stabilization and improvement. Patients should be monitored for PDT-related transient exudative response.

Background/purpose To report vitreous and epiretinal seeding of choroidal melanoma after transvitreal fine-needle aspiration biopsy (FNAB). Methods A 74-year-old Caucasian man with a medium-sized, dome-shaped choroidal melanoma without Bruch membrane rupture, retinal invasion, or vitreous seeding. Transvitreal FNAB was performed for cytopathologic evaluation using a long 27-gauge needle attached to a 10-mL syringe by connector tubing. After passing through the pars plana, vitreous cavity, neurosensory retina, and Bruch membrane, the needle was inserted into the tumor and aspiration was performed. Results Cytopathologic evaluation revealed spindle B melanoma cells, and the tumor was subsequently treated with an 18-mm round Iodine-125 radioactive plaque delivering a tumor apex radiation dose of 7,000 cGy. Transscleral FNAB for cytogenetic evaluation performed at the time of plaque application disclosed chromosome three monosomy and chromosome six and eight disomy. Vitreous pigmented cells were first noted 14 months after brachytherapy. Funduscopy and optical coherence tomography at 24 months after plaque radiotherapy showed extensive vitreous and preretinal pigmented seeding that completely covered the optic disk. Fine-needle aspiration biopsy of the vitreous confirmed the presence of malignant melanoma cells, and the right eye was enucleated. Histopathologic evaluation showed a totally necrotic choroidal melanoma and an extensive malignant epiretinal membrane that covered and extended into the substance of the optic nerve head and focally invaded the neurosensory retina. The patient developed liver metastasis 3 years after the initial presentation and died 10 months later. Conclusion This case demonstrates the rare development of extensive vitreous and preretinal seeding with retinal and optic nerve invasion after transvitreal FNAB of choroidal melanoma.

Purpose To report uveal melanoma (UM) metastasis to the contralateral ocular and periocular structures. Design Retrospective study. Participants Thirteen patients with UM metastasis to the contralateral ocular and periocular structures were included. Methods Clinical records were reviewed retrospectively. Main Outcome Measures The development and time to onset of contralateral ocular and periocular metastasis, systemic metastasis, and death. Results Of the 13 000 treated UM patients, 13 patients were diagnosed with UM metastasis to the contralateral ocular and periocular structures. Mean patient age at primary UM diagnosis was 60 years (median, 60 years; range, 37–87 years). The primary uveal melanoma was in the choroid (n = 11) or ciliary body (n = 2) and was treated with brachytherapy (n = 11), proton beam radiotherapy (n = 1), or enucleation (n = 1). Systemic metastasis developed in 11 patients (85%) at a mean of 66 months (median, 34 months; range, 12–216 months) after diagnosis of the primary UM. All 11 patients (100%) showed liver metastasis and 8 patients (62%) also showed extrahepatic metastasis. The sites of metastasis to the contralateral ocular or periocular structures included the choroid in 4 patients (31%), the orbit in 7 patients (54%), and the eyelid in 2 patients (15%). One patient with eyelid metastasis demonstrated concurrent conjunctival nodule. Mean time to diagnosis of contralateral ocular or periocular metastasis was 94 months (median, 48 months; range, 9–375 months). Contralateral choroidal metastasis was multifocal in 3 of 4 patients (75%). Of 7 patients with orbital metastasis, 5 showed extraocular muscle involvement with restricted ocular motility. Treatment for contralateral choroidal metastasis included brachytherapy (n = 2), transpupillary thermotherapy (n = 1), and observation (n = 1). Treatment for contralateral periocular (orbit or eyelid) metastasis was excision (n = 5), external beam radiotherapy (n = 2), and observation (n = 2). Of 13 patients, death was documented in 11 patients at a mean of 17 months (median, 9 months; range, 3–54 months) as a result of systemic UM metastasis (n = 10) or unrelated cause (n = 1). Conclusions Metastasis resulting from UM to the contralateral ocular and periocular structures is rare and generally occurs in patients with disseminated metastasis. Orbital tissue is the most common site of involvement, and these patients have short life expectancy.

PURPOSE To report a case of presumed choroidal nevus that eventually grew into melanoma in a patient with family history of choroidal melanoma and germline BAP1 mutation. METHODS Case report. RESULTS A 55-year-old healthy white woman with a family history of uveal melanoma in her father, paternal aunt, and paternal cousin was referred for evaluation of an asymptomatic small pigmented choroidal lesion in her right eye, measuring 2 mm × 2 mm in basal diameter and 1 mm in thickness. There were no clinical risk factors. The patient was advised routine monitoring but returned 4 years later with intermittent photopsia. The choroidal mass demonstrated growth and suggestive of transformation into melanoma, measuring 9 mm × 6 mm in basal diameter and 2.5 mm in thickness with overlying orange lipofuscin pigment and no associated subretinal fluid. Fine-needle aspiration biopsy disclosed Chromosome 3 mosaic monosomy and Chromosomes 6 and 8 disomy. Iodine 125 plaque radiotherapy was provided. Based on growth to melanoma and strong family history of uveal melanoma, BAP1 germline mutation testing was performed, and the results were positive. CONCLUSION This case demonstrates growth of a presumed choroidal nevus into melanoma in the setting of underlying germline BAP1 mutation. We suggest that small pigmented choroidal lesions be monitored closely in patients with germline BAP1 mutation or with family history of uveal melanoma, even in the absence of known local risk factors predictive of tumor growth.

Purpose To explore clinical features and outcomes of ocular surface squamous neoplasia (OSSN) treated with primary interferon (IFN)-α2b, based on patient cigarette smoking status. Methods Retrospective nonrandomized, interventional cohort study on 212 consecutive tumors in 194 patients, all of whom were treated with topical and/or injection IFNα2b. Results There were 88 tumors in 76 patients with current or past smoking history (smokers) and 124 tumors in 118 nonsmoking patients (nonsmokers). A comparison (smokers vs. nonsmokers) revealed smokers with more frequent bilateral disease (16% vs. 3%, P = 0.003), more frequent involvement of inferior forniceal (34% vs. 21%, P = 0.03) and inferior tarsal conjunctiva (38% vs. 24%, P = 0.04), greater mean number of clock hour involvement (4.1 vs. 3.5 clock hours, P = 0.04), and greater dome growth pattern (30% vs. 15%, P = 0.01). There was no difference regarding method of IFNα2b administration as topical (61% vs. 71%, P = 0.14), injection (10% vs. 6%, P = 0.32), or combination topical/injection (28% vs. 23%, P = 0.33). A comparison revealed smokers with more frequent recurrence after initial response (23% vs. 13%, P = 0.04). There was no difference regarding initial tumor response or time to response, treatment side effects, or systemic outcomes. Conclusions Regarding ocular surface squamous neoplasia, smokers more often display bilateral, dome-shaped tumors with inferior forniceal or tarsal involvement, and greater extent than nonsmokers. After treatment with topical and/or injection IFNα2b, control is equivalent, but smokers show greater recurrence.

Purpose To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. Design Multicenter retrospective observational case series. Participants Sixty-three patients with SIC in 1 eye. Methods Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. Main Outcome Measures Standardized grading of imaging features. Results Mean age at presentation was 56 ± 15 years (range, 12–83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month–25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 μm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. Conclusions In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

Purpose To determine factors predictive of visual outcome in patients with circumscribed choroidal hemangioma treated with photodynamic therapy (PDT). Design Retrospective case series. Participants Seventy-nine patients with circumscribed choroidal hemangioma treated with PDT. Methods Patients with circumscribed choroidal hemangioma treated with PDT were identified, and factors predictive of final visual acuity were assessed. Main Outcome Measures Factors predictive of final visual acuity of 20/40 or better versus 20/50 or worse. Results Seventy-nine eyes of 79 patients with circumscribed choroidal hemangioma were treated with PDT. All tumors were unilateral and posterior to the equator. Mean largest basal diameter was 5.7 mm (range, 2.0–10.0 mm); mean thickness was 3.0 mm (range, 1.4–4.5 mm). A total of 116 PDT sessions were performed (mean, 1.5 sessions; range, 1.0–7.0 sessions). Standard duration PDT was used in most cases (83 seconds; n = 110/116 [95%]). Mean follow-up was 43 months. Of 79 patients, 49 (62%) demonstrated good visual acuity (≥20/40) and 30 (38%) showed intermediate to poor visual acuity (≤20/50) after PDT. A comparison (final visual acuity, good vs. intermediate to poor) revealed a statistically significant difference in baseline features of photopsia (100% vs. 0%; P = 0.04), initial visual acuity of 20/40 or better (77% vs. 23%; P Conclusions In this comparative analysis, PDT was an effective treatment method for circumscribed choroidal hemangioma. Good final visual outcome (≥20/40) was correlated with good baseline visual acuity, smaller tumor size, lack of CME, and lack of treatment before PDT.

Purpose Since the original description of “dacryadenoma” by Jakobiec and associates, the data on this unusual epibulbar lacrimal gland lesion remain sparse. The aim of this study was to characterize clinically, morphologically, and immunohistochemically this isolated epibulbar lacrimal gland lesion. Design Retrospective observational case series. Methods Institutional pathology records between 2000 and 2019 were searched for all cases of isolated epibulbar lacrimal gland lesions. Tissue from 3 normal lacrimal glands and 1 complex choristoma were included for comparative analysis. Clinical, histopathologic, and immunohistochemical findings were recorded. Results Four patients with isolated epibulbar lacrimal gland lesions, 2 male and 2 female, with a median age of 18 years (range, 12-57) were identified. All patients presented with recent onset of unilateral pink-to-orange, well-circumscribed subepithelial juxtaforniceal (3/4, 75%), or nasal (1/4, 25%) bulbar conjunctival nodules, which were asymptomatic (3/4, 75%) or associated with foreign body sensation (1/4, 25%). When compared with the normal lacrimal gland and complex choristoma, all isolated epibulbar lacrimal gland lesions were composed predominantly of variably dilated, branching tubular structures with pseudo-apocrine snouts, and either totally absent (2/2, 50%) or rare (2/2, 50%) ducts and rare acinar zymogen granules (3/4, 75%). Conclusion Our study confirms that a subset of isolated epibulbar lacrimal gland lesions differs morphologically and immunohistochemically from normal lacrimal gland tissue and the lacrimal gland in a complex choristoma. These differences range from subtle to overt, suggesting that isolated epibulbar lacrimal gland lesions may have originated from precursor cellular elements indigenous to the conjunctiva (hamartia) and grew into disorganized lacrimal gland tissue.

Summary The role of p16 in the diagnosis and prognosis of conjunctival melanocytic lesions in the context of other clinical and immunohistochemical parameters has not been systematically explored. This study was conducted to determine whether p16 is a useful parameter in the diagnosis and prognosis of conjunctival melanocytic nevi and melanoma, either independently or as a component of immunohistochemical panels. Sixty-one patients underwent 61 biopsies for conjunctival melanocytic lesions between 2014 and 2018. Pathologic diagnoses were melanoma (n = 25, 41%), nevus (n = 21, 34%), and conjunctival melanocytic lesion of uncertain malignant potential (n = 15, 25%). The biopsies were assessed for expression of p16, SOX10, HMB45, and Ki-67. In a multivariable model, the parameters most predictive of melanoma versus nevus were diffuse HMB45 staining (odds ratio [OR] = 45, confidence interval [CI] = 4.4–457, P = .02] and p16 nuclear H-score≤115 (OR = 9.5, CI = 1.2–77; P = .04). There was no association of p16 expression with melanoma thickness. Next-generation sequencing identified no CDKN2A mutations or copy number alterations in 12 conjunctival melanomas, including the tumors with absent p16 expression. This study demonstrates that p16 immunohistochemical stain is useful in distinguishing conjunctival melanocytic nevi from melanoma, particularly in combination with HMB45. P16 expression does not appear to correlate with CDKN2A status and melanoma thickness.

Lacrimal drainage apparatus melanoma is a rare entity that may arise primarily or, more commonly, as secondary involvement from melanoma originating elsewhere. Conjunctival melanoma may involve the lacrimal drainage apparatus (LDA) via spread along the canalicular epithelium, separate in situ processes, or direct invasion. Only seven cases exist in the literature where conjunctival melanoma remotely recurred in the LDA. We report three additional patients, two with invasive conjunctival melanoma and one with primary acquired melanosis (PAM) with severe atypia/melanoma in situ, who developed LDA melanoma at 5, 8, and 16 years after initial treatment of conjunctival melanoma. This report confirms the ability of conjunctival melanoma to give rise to spatially and temporally remote LDA melanoma despite adequate local treatment, and reviews the proposed mechanisms and associated characteristics of LDA recurrence in conjunctival melanoma.

Purpose To describe the clinical and imaging characteristics, pathologic features, and management options of retinal pigment epithelium (RPE) adenoma/adenocarcinoma. Design Retrospective case series. Participants Fifty-one patients with RPE adenoma/adenocarcinoma. Methods Treatment options for the patients included observation, partial lamellar sclerouvectomy (PLSU), enucleation, and others. Main Outcome Measures Factors related to visual acuity (VA) outcomes (>2 Snellen lines loss, poor final VA [≤20/200], good final vision [≥20/40]), tumor growth, and need for enucleation. Results The mean patient age at diagnosis was 51 years, and the majority of patients were white (40/51, 78%) and female (34/51, 67%). Primary management included observation (29/51, 57%), PLSU (9/51, 18%), enucleation (4/51, 8%), or others (9/51, 18%). Outcomes revealed decreased VA (10/32, 31%), poor final VA (17/32, 53%), good final VA (11/32, 34%), tumor growth (12/25, 48%), and need for enucleation (7/51, 14%). By multivariable analysis, features predictive of decreased VA included increasing baseline tumor thickness (P = 0.01) and presence of vitreous hemorrhage (P = 0.05). Factors predictive of poor final VA included presence of exudative retinal detachment (P = 0.004), baseline VA 20/50 to 20/150 (P = 0.008), and baseline VA ≤20/200 (P = 0.01). Absence of feeding and/or draining vessel was predictive of good VA (P = 0.004). Tumor growth was associated with multiple treatments (P = 0.02). Increased tumor thickness (P = 0.03) and presence of exudative retinal detachment (P = 0.01) were predictive of enucleation. Conclusion RPE adenoma/adenocarcinoma can simulate choroidal melanoma. Greater tumor thickness, vitreous hemorrhage, exudative retinal detachment, and poor baseline VA predict worse visual outcome and greater risk for enucleation.

PURPOSE To investigate the clinical features and outcomes for conjunctival melanoma based on patient age. METHODS A retrospective review of patients with conjunctival melanoma managed at a single tertiary referral center from April 18, 1974, to September 9, 2019. Clinical features and outcomes were compared by patient age category at presentation (young ≤45 years, middle-aged 46-69 years, and older ≥70 years), with Kaplan-Meier and Cox proportional hazard analysis [hazard ratio (95% confidence interval)]. RESULTS There were 629 patients categorized as young in 130 (21%), middle-aged in 278 (44%), and older in 221 (35%). A comparison by age category (young vs. middle-aged vs. older) revealed that older patients had melanoma with greater number of affected quadrants (1.7 vs. 1.8 vs. 2.0, P = 0.001) and clock hours (3.9 vs. 4.2 vs. 5.2, P = 0.001). All patients were treated with surgical excision, with no difference in requirement for additional medical or radiation therapy. By 10-year Kaplan-Meier outcomes, older patients had more frequent visual acuity loss ≥3 lines (11% vs. 28% vs. 64%, P < 0.001) and local tumor recurrence (38% vs. 46% vs. 70%, P < 0.001). Hazard ratio for the oldest age group (age ≥70) revealed a 7.76-fold (3.33-18.09) increased risk for visual acuity loss (P < 0.001), and a 2.08-fold (1.32-3.28) increased risk of local tumor recurrence (P = 0.002). There was no difference by age in risk for enucleation, exenteration, locoregional lymph node involvement, distant systemic metastasis, or death. CONCLUSIONS Older patients with conjunctival melanoma present with more extensive disease and have increased risk for visual acuity loss and local tumor recurrence.

Purpose: To report clinical features, pathology characteristics, and treatment outcomes of five patients with Rosai-Dorfman disease (RDD). Methods: A retrospective case series of patients with RDD from the Ocular Oncology Service of Wills Eye Hospital between 1974 and 2018. Results: There were six eyes of five patients (3 males, 2 females) with ophthalmic manifestations of RDD. The mean age at the initial presentation was 33 years (median 35, range 10–52 years). Before referral, the tumor was initially suspected to be lymphoma (n = 3), idiopathic orbital inflammation (n = 2), or pterygium (n = 1). The disease was unilateral (n = 4) or bilateral (n = 1). The mean duration of symptoms was 9 months (median 8, range 5–24 months). The disease produced nodules in the conjunctiva (n = 4) or orbit (n = 2). Two patients with conjunctival involvement had corneal involvement. One patient with bilateral conjunctiva lesions demonstrated bilateral orbital involvement and bilateral anterior uveitis. The mean tumor basal dimension was 13 mm (median 9, range 6–27 mm) for conjunctiva lesions and 37 mm (median 37, range 34–40 mm) for orbital lesions. The main symptom (per patient) included proptosis (n = 2), palpable mass (n = 1), and foreign body sensation (n = 2). No patient experienced pain or tenderness. Palpable, nontender lymphadenopathy was detectable in two patients in the cervical and inguinal lymph nodes. Systemic involvement with paranasal sinusitis and mediastinal/pulmonary lymphadenopathy occurred in two patients, both with orbital involvement. Surgical resection was performed for all patients. At a mean follow-up of 31 months (median 12, range, 10–76 months) after the surgery, tumor control was achieved in all six eyes without local recurrence. Conclusion: In this series of six eyes with RDD, patients with orbital and/or intraocular disease were more likely to demonstrate lymphadenopathy and systemic involvement, while those with unilateral perilimbal conjunctival tumors remained localized.

Purpose To determine the association between vitreoretinal lymphoma and systemic lymphoma (SL). Methods Single-center retrospective review of medical records. Results Of 95 patients with vitreoretinal lymphoma, 18 (19%) had associated SL (SL group) and 77 (81%) were not associated with SL (no SL group). The most common sites of SL were skin (n = 5), testis (n = 2), liver and breast (n = 2), and others (n = 9). A comparison (SL group vs. [vs.] no SL group) revealed no difference in demographic or ocular findings at initial visit. In the SL group, SL occurred before the onset of ocular symptoms in 14 (78%) patients with mean interval of 86 months (median 61, range 5-286 months) or after ocular symptoms in 4 (22%) patients with mean interval of 19 months (median 12, range 7-44 months). A comparison revealed no difference in overall frequency of pre-existing or eventual central nervous SL (50% vs. 53%, P = 0.99); however, the SL group demonstrated central nervous SL more often after onset of ocular symptoms (78% vs. 17%, P = 0.001). A comparison found no difference in treatment methods, response of vitreoretinal lymphoma to treatment, final visual outcome, or death rate. Conclusion We found 19% of patients with vitreoretinal lymphoma demonstrate related SL, and there was no difference in demographics, clinical features, or response to treatment, compared to those not associated with SL.

Purpose To report a rare case of intraocular schwannoma with extrascleral extension in a patient with juvenile idiopathic arthritis and to review the literature for this topic. Methods Case report. Results A 19-year-old male with a history of juvenile idiopathic arthritis was referred for diagnosis and management of an episcleral mass, initially thought to be focal nodular scleritis. The ocular surface of the right eye revealed an elevated amelanotic episcleral nodule inferonasally, with thin strands of overlying sclera, feeding episcleral vessels, and measuring 11 mm × 11 mm in diameter and 5 mm in thickness. Ophthalmoscopic examination revealed a minimally pigmented ciliochoroidal tumor measuring 13 mm in diameter and 11.4 mm in total thickness and without associated subretinal fluid, orange pigment, or drusen. Ultrasound biomicroscopy and anterior-segment optical coherence tomography confirmed a solid mass with scleral disruption and extraocular extension. Shave biopsy revealed palisading spindle cells and interspersed eosinophilic fibrillary cytoplasmic processes, forming Verocay bodies. The specimen stained positive for S-100 and negative for Melan-A, consistent with benign schwannoma. Observation was recommended. Conclusion Intraocular schwannoma is a rare, benign uveal tumor that can demonstrate extrascleral extension, mimicking inflammatory and malignant neoplastic processes. Clinical diagnosis is challenging, and tissue biopsy is required for definite diagnosis.

IMPORTANCE The impact of tumour thickness on radiation complications following plaque radiotherapy for uveal melanoma in the anti-vascular endothelial growth factor (VEGF) era remains unknown. BACKGROUND To evaluate treatment outcomes following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma based on initial tumour thickness. DESIGN This was a retrospective, interventional case series. PARTICIPANTS Patients with uveal melanoma were included in this study. METHODS A review of medical records was conducted of patients with uveal melanoma treated with plaque radiotherapy and prophylactic intravitreal bevacizumab from 7 July 2000 to 2 November 2018. MAIN OUTCOMES MEASURES Radiation-related outcomes of cystoid macular oedema (CME), radiation maculopathy, papillopathy, retinopathy, iris neovascularization (NVI) and neovascular glaucoma (NVG) were compared based on tumour thickness (small [ 8.0 mm]). RESULTS Of 1131 eyes, 341 (30%) had small, 633 (56%) medium and 157 (14%) large melanoma. Comparison (small vs medium vs large) at 4 years following radiotherapy revealed large melanoma with greater Kaplan-Meier estimated risk of CME (37% vs 37% vs 63%, P

PURPOSE To determine the association of Fitzpatrick skin type (FST) with conjunctival melanoma. METHODS Retrospective case series of 540 patients with conjunctival melanoma to assess clinical features and outcomes per FST. RESULTS The FST was Type I (n = 126, 23%), II (n = 337, 62%), III (n = 56, 10%), IV (n = 8, 2%), V (n = 12, 2%), and VI (n = 1

Purpose To determine outcomes after photodynamic therapy (PDT) for choroidal metastasis. Design Retrospective interventional case series. Participants Forty-three patients with 40 eyes harboring 58 choroidal metastases. Methods Treatment with standard fluence PDT using verteporfin. Main Outcome Measures Tumor control and visual outcomes. Results The primary cancer originated in the lung (n = 17 [39%]), breast (n = 16 [37%]), kidney (n = 3 [8%]), thyroid (n = 2 [6%]), and other sites (n = 5 [10%]). The mean patient age at entry was 61 years. Ocular symptoms included decreased visual acuity (n = 23 [53%]), visual field defect (n = 2 [5%]), floaters (n = 7 [16%]), flashes (n = 3 [7%]), and asymptomatic (n = 8 [19%]). The median entering visual acuity (Snellen equivalent) was 20/40. The median tumor diameter was 5.0 mm, and median thickness by ultrasonography was 2.0 mm. The median distance to the optic disc was 3.0 mm, and that to the foveola was 2.0 mm. Of the 43 patients, 35 maintained follow-up (40 eyes, 45 tumors), and PDT achieved tumor control with 1 session (n = 32 tumors [71%]) or 2 sessions (n = 3 tumors [7%]) and failed to achieve regression (n = 10 tumors [22%]). The 10 metastases for which treatment failed were managed further with plaque radiotherapy (n = 3), proton beam radiotherapy (n = 1), external beam radiotherapy (n = 1), systemic chemotherapy (n = 4), and observation (patient preference; n = 1). A comparison of clinical features for tumor control (PDT alone vs. PDT plus additional therapy) revealed those controlled with PDT alone were more likely to be adenocarcinoma (73% vs. 30%; P = 0.02) and those eyes were more like to achieve final visual acuity of 20/20 to 20/40 (66% vs. 30%; P = 0.03), with better median final Snellen visual acuity (20/30 vs. 20/70; not significant). Primary cancer site or ocular tumor features (size, location, color, shape, related subretinal fluid) did not impact tumor control. In the entire group of 40 eyes, visual acuity improved or remained stable in 28 (70%) and decreased in 12 (30%), related to subfoveal scar, persistent subretinal fluid, reactive exudation, radiation maculopathy, and brain metastasis. At last follow-up (mean, 20 months), of the entering 43 patients, 9 (21%) were alive and 34 (79%) had died of systemic metastasis. Conclusions Photodynamic therapy with verteporfin is an effective outpatient method for small to medium choroidal metastatic tumors, providing tumor control in 78% of eyes and visual outcome of 20/20 to 20/40 in 66% of eyes.

Background: Muir-Torre syndrome (MTS) is defined clinically as the association of cutaneous sebaceous neoplasm and visceral malignancy. Ancillary tests are considered crucial for diagnosis. Although screening guidelines for MTS, including the Mayo MTS scoring system, have been proposed, there are no ophthalmic site-specific guidelines. Summary: A literature review conducted by PubMed search for articles describing patients with periocular sebaceous neoplasm and MTS disclosed 31 publications describing 60 patients, 36 (60%) of whom fulfilled clinical criteria for MTS, 6 (10%) whose diagnosis was based on screening ancillary studies, 14 (23%) who fulfilled clinical criteria and had supporting screening ancillary studies, and 4 (7%) who fulfilled clinical criteria and had supporting diagnostic genetic testing. Most patients were male (34 vs. 15 females), with a median age of 59 years (range 37–79 years). The most common diagnosis was sebaceous carcinoma (40/60, 67%), followed by sebaceous adenoma (16/60, 27%), followed by other tumors with sebaceous differentiation (4/60, 6%). The periocular lesions were identified prior to visceral malignancy in 10 out of 45 (22%) cases, after visceral malignancy in 34 out of 45 (76%) cases, and concurrently with visceral malignancy in 1 out of 45 (2%) cases. Immunohistochemistry for mismatch repair proteins was performed in 41 out of 60 (68%) and 14 out of 38 (37%) of the tumors had lost MSH2. Based on Mayo-MTS scores of 2 or greater, and after removing visceral malignancies not included in their scoring algorithm, 26 out of 30 of patients (87%) with complete data were considered to be appropriate candidates for further work-up. A survey of current practice was conducted by questionnaires, distributed to ophthalmic pathologists, ocular oncologists, and oculoplastic surgeons from national and international professional societies. Of the 103 physicians who participated in the survey, 91 (88%) felt that MTS evaluation guidelines were not sufficiently clear. Key Messages: Our findings suggest that Mayo MTS screening guidelines may be applicable to periocular sebaceous neoplasms. The uncertainty of ophthalmic specialists about optimal screening guidelines for MTS reflects the heterogeneity of defining criteria for MTS and limited molecular genetic data. Larger studies with detailed clinical, histopathologic, and molecular genetic data are required to formally assess screening guidelines for MTS in patients with periocular sebaceous neoplasms.

To analyze visual outcomes after treatment of choroidal hemangioma in the pre-photodynamic therapy (PDT) era versus PDT era.Retrospective, comparative case series.A total of 458 patients with circumscribed choroidal hemangioma.Comparison of hemangioma managed in the pre-PDT (1967-2001) era versus PDT (2002-2018) era.Visual acuity outcome.A total of 458 tumors were treated over this 51-year period. A comparison (pre-PDT [n = 220 cases] vs. PDT [n = 238 cases]) revealed PDT era patients were of older mean age (48.9 vs. 53.8 years, P = 0.002) and were more likely to have systemic hypertension (17.7% vs. 33.8%, P0.001), tumor location in the macula (57.4% vs. 67.5%, P = 0.01), subretinal fluid on OCT (33.3% vs. 70.7%, P = 0.01), and greater extent of overlying lipofuscin (P = 0.001). Findings of tumor basal diameter and thickness and fluorescein and indocyanine green angiography were no different in the 2 eras. Treatment (pre-PDT vs. PDT) included argon laser photocoagulation (42.1% vs. 0.4%), PDT (0% vs. 43.8%), transpupillary thermotherapy (0% vs. 0.4%), plaque radiotherapy (7.0% vs. 5.2%), external beam radiotherapy (1.4% vs. 1.3%), enucleation (0.9% vs. 0.4%), and observation (48.6% vs. 47.6%). After treatment, patients in the PDT era demonstrated better mean logarithm of the minimum angle of resolution visual acuity (1.28 vs. 0.51, P0.001) (Snellen equivalent 20/400 vs. 20/63, P0.001). Final visual acuity was ≥20/40 for those with entering vision of ≥20/40 (59.6% vs. 74.7%, P = 0.001) and for those with entering vision of 20/50-20/200 (25.4% vs. 47.3%, P0.001).Management of choroidal hemangioma in the PDT era has allowed for significantly better visual outcome compared with the pre-PDT era, with mean final visual acuity of 20/400 (pre-PDT era) versus 20/63 (PDT era).

Purpose To report development of choroidal neovascular membrane at the site of diagnostic transvitreal fine-needle aspiration biopsy of subretinal pigment epithelial infiltrates in an eye with vitreoretinal lymphoma. Methods Case report. A 75-year-old white woman with 14-month history of bilateral vitritis. Results Examination showed vitreous infiltration in both eyes and yellow-white subretinal pigment epithelial infiltrates temporally in the left eye. Visual acuity was 20/400 in both eyes. Transvitreal fine-needle aspiration biopsy of subretinal pigment epithelial infiltrate in the left eye using a long 27-gauge needle attached to a 10-mL syringe revealed large B-cell lymphoma. Treatment was initiated with monthly intravitreal injections of melphalan (10 μg/0.05 mL) to both eyes. One month after first injection, visual acuity in the left eye had decreased to hand motion, and new ill-defined patches of retinal whitening were noticeable in the temporal macular area. Intravenous fluorescein angiography and optical coherence tomography angiography showed large choroidal neovascular membrane temporally at the site of previous fine-needle aspiration biopsy. Four monthly injections of intravitreal bevacizumab (1.25 mg/0.05 mL) resulted in complete regression of choroidal neovascular membrane with improvement of visual acuity to 20/100 in the left eye. Conclusion This case demonstrates the rare development of choroidal neovascular membrane at the site of diagnostic transvitreal fine-needle aspiration biopsy of subretinal pigment epithelial infiltrates in an eye with vitreoretinal lymphoma.

Purpose: To describe the outcome of ultra-low-dose (boom-boom) radiotherapy for choroidal lymphoma. Methods: Retrospective series of three consecutive patients with biopsy-proven choroidal lymphoma treated with ultra-low-dose radiotherapy. Results: The three patients (two male, one female) of mean age 70 years (range, 64–74 years) demonstrated presenting visual acuity in the affected eye between 20/40 and 20/50. The choroidal lymphoma was unilateral in all cases and presented with multifocal yellow patchy choroidal infiltration, located in all four quadrants and measuring mean 2.9 mm (range, 1.9–4.0 mm) in thickness by ultrasonography. Anterior epibulbar extension of 5 mm diameter was noted in one case. By enhanced depth imaging optical coherence tomography, the choroidal infiltration demonstrated classic undulating appearance (n = 3), with subretinal fluid (n = 2) and intraretinal edema (n = 1). There was no systemic lymphoma in any case. Biopsy was performed in all three cases and was diagnostic (n = 1) or suggestive (n = 2) of B-cell lymphoma. Management involved ultra-low-dose radiotherapy (4 Gy delivered in two fractions, “boom-boom”). On follow-up (mean = 14 months, range = 6–24 months), complete tumor regression on ophthalmoscopy was documented in all three cases, with enhanced depth imaging optical coherence tomography and ultrasonography demonstrating evidence of lymphoma resolution and visual acuity improvement to 20/25–20/40. There were no radiation complications. Conclusion: In this small case series, ultra-low-dose (boom-boom) radiotherapy was effective for choroidal lymphoma with favorable response and minimal side effects.

Purpose:To analyze risk of nevus transformation into melanoma per millimeter increment.Methods:Retrospective analysis of 3,806 choroidal nevi for transformation into melanoma per incremental millimeter thickness (flat [≤1.0 mm], thin [1.1–2.0 mm], thicker [2.1–3.0 mm], and thickest [>3.0 mm])Results

Purpose:To use multimodal imaging for identification of risk factors for choroidal nevus transformation into melanoma.Methods:Retrospective chart review of 3806 consecutive choroidal nevi with imaging and 2355 choroidal nevi with additional follow up to identify factors predictive of transformation

To evaluate the clinical and pathologic characteristics of conjunctival myxoid lesions, with specific focus on PRKAR1A studies, in order to distinguish neoplastic conjunctival myxoma from other myxoid conjunctival lesions.A retrospective, interventional, multicenter study of all patients with conjunctival myxoma, conjunctival stromal tumor, or reactive fibromyxoid proliferation diagnosed during 1988-2018. Patient and family medical histories and clinical and pathologic characteristics of excised lesions were assessed.There were 28 patients with conjunctival myxoid lesions diagnosed as myxoma (16/28), conjunctival stromal tumor (10/28), or reactive fibromyxoid proliferation (2/28). The patients with abundant myxoid matrix lesions (14/28, 50%) were younger (mean 49 [range 23-68] years) than those with scant-to-moderate myxoid matrix lesions (14/28, mean 61 [range 18-82] years; P = .04). Abundant myxoid matrix lesions more likely contained predominantly stellate cells (6/14 [43%] vs 0/14 [0%]; P = .05) and fibrillar collagen (13/14 [93%] vs 2/14 [14%]; P.0001), conforming to the standard morphologic definition of myxoma. Absence of PRKAR1A protein expression was found in 2 lesions with morphologic features of myxoma (2/14, 14%), 1 of which demonstrated a pathogenic mutation in the PRKAR1A gene. There was no difference between the lesions with respect to other clinical and pathologic parameters.PRKAR1A plays a role in the development of a subset of conjunctival myxomas, particularly in tumors fulfilling stringent morphologic criteria for myxoma. With the exception of PRKAR1A studies, current immunohistochemical panels cannot reliably distinguish between neoplastic conjunctival myxomas and other myxoid lesions, underscoring the importance of morphology in establishing accurate diagnosis.

Purpose: To evaluate interval between primary cancer diagnosis and uveal metastasis and assess survival outcomes based on whether the primary cancer was diagnosed before or after uveal metastasis. Methods: In this retrospective analysis, all patients with uveal metastasis evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA between February 1, 1974 and June 1, 2017 were included. Features and outcomes based on timing of primary cancer diagnosis, whether before or after diagnosis of uveal metastasis, were assessed. Results: A total of 2214 uveal metastases were diagnosed in 1310 eyes of 1111 consecutive patients. Primary cancer was known prior to uveal metastasis in 742 patients (67%) and not known in 369 (33%). Of those not known, the primary cancer was later found in 192 patients (17%) and never found in 177 patients (16%). For those with known primary cancer, mean interval from primary cancer diagnosis to uveal metastasis was 5.2 years with differences in primary sites of gastrointestinal (2.1 years, p = 0.003), lung (2.2 years, p

Purpose: The aim of this study was to investigate factors predictive of subretinal fluid (SRF) resolution in Coats disease. Design: Retrospective cohort study. Methods: Institutional review board-approved review of patients diagnosed with Coats disease demonstrating SRF (stage 3–5) at a single center from November 1973 to July 2018 with comparison of eyes that had resolution of SRF to those in which SRF persisted. Results: There were 177 cases (154 males, 87%) of Coats disease diagnosed at a mean age of 8 years. After a mean follow-up of 62 months, SRF resolved in 110 (62%) and persisted in 67 (38%) eyes. Comparison (resolved SRF vs persistent SRF) revealed classification as stage 3A [63 (57%) vs 20 (29%)], stage 3B [47 (43%) vs 40 (60%)], or stage 4 [0 (0%) vs 7 (11%)] (P

Purpose: To investigate features and outcomes of circumscribed choroidal hemangioma by patient age. Methods: Retrospective review of circumscribed choroidal hemangioma from 3/29/1967–6/4/2018 based on age at presentation (≤20 vs. >20–50 vs. >50 years). Results: There were 458 circumscribed choroidal hemangiomas diagnosed at mean age (13 vs. 41 vs. 64 years, p

Purpose: To describe the occurrence of bilateral primary uveal melanoma in 2 patients with mutation on the gene encoding BRCA1-associated protein 1 (BAP1). Methods: Retrospective chart review of patients with bilateral primary uveal melanoma and subsequent positive germline BAP1 mutation. Results: There were 2 patients with bilateral uveal melanoma and BAP1 germline positivity. Neither patient demonstrated oculodermal melanocytosis. Patient 1 underwent enucleation of his right eye (OD) at the age of 44 years for a 9.6-mm-thick choroidal melanoma. He returned 4 years later with a 10.0-mm-thick choroidal melanoma in his left eye (OS) and was treated with plaque radiotherapy. He had a strong family history of cancer, and clinical testing for germline BAP1 mutation identified a pathogenic mutation in BAP1. At the 18-month follow-up, visual acuity was 20/200 OS without evidence of systemic metastasis. Patient 2 initially presented at age 54 years with extensive, diffuse iris melanoma OD, initially treated with plaque radiotherapy, but local recurrence after 3 years necessitated enucleation. Four years later, a 6.0-mm-thick ciliary body melanoma OS was found and successfully treated with plaque radiotherapy. Clinical testing for germline BAP1 mutation identified a pathogenic mutation in BAP1. At the 8-year follow-up, visual acuity was 20/40 OS without evidence of local recurrence or systemic metastasis. The patient expired secondary to an unrelated brain infarction. Conclusion: Bilateral uveal melanoma is exceedingly rare. Patients with bilateral uveal melanoma, especially when coincident with remote systemic cancers or a family history of cancer, should be evaluated for germline BAP1 mutation. Lifelong monitoring for related systemic malignancies is advised.

Purpose: To evaluate the likelihood of germline retinoblastoma in patients presenting with solitary unilateral retinoblastoma, based on age at presentation. Methods: This retrospective case series of 482 consecutive patients presenting with solitary unilateral retinoblastoma analyzed the likelihood of germline retinoblastoma, defined as family history of retinoblastoma, germline retinoblastoma mutation documented on genetic testing, and/or development of bilateral disease and/or additional new tumors. This analysis was based on age at presentation (0 to 12 months vs older than 12 to 24 months vs older than 24 to 36 months vs older than 36 months) and a sub-study was conducted on infant age at presentation (0 to 3 months vs older than 3 to 6 months vs older than 6 to 9 months vs older than 9 to 12 months). Results: Of the overall group (482 consecutive patients) with solitary unilateral retinoblastoma, there were significantly different findings in the youngest age group (0 to 12 months old) with greater family history of retinoblastoma (10% vs 2% vs 1% vs 2%, P = .004), smaller median basal diameter (18.0 vs 20.0 vs 20.0 vs 20.0 mm, P = .014), smaller median tumor thickness (8.7 vs 10.0 vs 11.5 vs 10.0 mm, P = .002), greater macular tumor location (33% vs 16% vs 10% vs 8%, P < .001), and greatest likelihood of germline mutation (29% vs 17% vs 8% vs 9%, P = .001). By comparison, patients 1 year and younger (vs older than 1 year) demonstrated a 2.96 odds ratio (OR) ( P = .001) for likelihood of germline retinoblastoma. For those classified as infants (1 year and younger) (n = 132 consecutive patients), the youngest patients (0 to 3 months old) demonstrated the greatest likelihood for germline mutation (61% vs 20% vs 24% vs 22%, P = .009) and greatest odds ratio (5.52, P = .002) compared to patients older than 3 to 12 months. Conclusions: The youngest patients with solitary unilateral retinoblastoma showed the greatest likelihood of germline disease when evaluating all patients (1 year and younger vs older than 1 year of age) (OR = 2.96) and the substudy of infants (3 years and younger vs older than 3 to 12 months old) (OR = 5.52). [ J Pediatr Ophthalmol Strabismus . 2021;58(6):355–364.]

PURPOSE: To investigate clinical features and outcomes of conjunctival melanoma classified by tumour origin. METHODS: Retrospective review of conjunctival melanoma patients at a single ocular oncology centre between April 18, 1974 and September 9, 2019. Lesions were divided into three tumour origin groups (primary acquired melanosis [PAM], nevus, and de novo) and clinical features and outcomes were compared. RESULTS: There were 629 patients with conjunctival melanoma that arose from PAM (n = 476, 76%), nevus (n = 59, 9%), or de novo (n = 94, 15%). A comparison (PAM vs. nevus vs. de novo) revealed patients with tumours arising from PAM presented with older mean age (62 vs. 52 vs. 55 years, p

Purpose: The aim of this study was to evaluate tumor control of OSSN with topical IFNα2b alone based on tumor configuration (flat versus (vs.) dome-shaped). Methods: Retrospective, nonrandomized, interventional cohort study on 64 consecutive tumors in 63 patients with OSSN treated with topical IFNα2b. Topical IFNα2b (1 million international units/cc) was compounded and provided by the Thomas Jefferson University Hospital Pharmacy to be refrigerated and applied 4 times daily until biomicroscopic evidence of tumor resolution was observed. Results: The tumor configuration was flat (n = 15, 23%) or dome-shaped (n = 49, 77%). A comparison (flat vs. dome-shaped) revealed dome-shaped with older mean patient age at presentation (62 vs. 70 years, P = 0.04), greater patient history of smoking (13% vs. 42%, P = 0.04), greater corneal involvement (7% vs. 82%, P < 0.001), larger mean basal diameter (5.5 vs. 12.4 mm, P = 0.001) and mean thickness (1.9 vs. 4.3, P = 0.002), and longer mean duration IFNα2b therapy (3.7 vs. 6.3 months, P = 0.002). There was no difference in mean follow-up time (22.2 vs 23.1 months) or time to complete response (5.0 vs. 6.1 months). There was no difference in achievement of complete tumor control with IFNα2b alone (93% vs. 96%). There were no cases with metastasis or death. Conclusion: Topical IFNα2b alone shows excellent overall tumor control of 95% with no difference in efficacy based on tumor configuration.

The aim of this study was to evaluate outcomes of conjunctiva melanoma based on the American Joint Committee on Cancer Classification (AJCC) 8th edition.Retrospective interventional case series.Outcomes analysis of 425 patients.In this analysis of 425 patients with conjunctival melanoma, there were 266 (63%) patients classified as T1, 75 (18%) as T2, 84 (20%) as T3, and 0 (0%) as T4. A comparison (T1 vs T2 vs T3) revealed that history of primary acquired melanosis was more common in T2 (81% vs 96% vs 81%; P = 0.01) and conjunctival nevus more common in T1 (20% vs 9% vs 11%; P = 0.03). Of 381 patients with follow-up (mean of 57.6 months), comparison revealed higher T category with increasing local recurrence/new tumor (30% vs 43% vs 49%; P = 0.004), increasing exenteration (3% vs 9% vs 28%; P 0.001), increasing melanoma-related locoregional lymph node metastasis (2% vs 7% vs 12%; P = 0.001), increasing melanoma-related systemic metastasis (9% vs 25% vs 23%; P 0.001), and increasing melanoma-related death (4% vs 12% vs 18%; P 0.001). A comparison at 10 years revealed visual acuity loss of3 lines (32% vs 42% vs 63%; P 0.001), melanoma recurrence/new tumor (47% vs 70% vs 74%; P 0.001), exenteration (4% vs 24% vs 46%; P 0.001), melanoma-related locoregional lymph node metastasis (3% vs 13% vs 25%; P 0.001), melanoma-related systemic metastasis (13% vs 45% vs 40%; P 0.001), and melanoma-related death (8% vs 22% vs 37%; P 0.001).Based on the AJCC 8th edition of conjunctival melanoma, the 10-year risk per T category significantly increased for visual acuity loss of3 lines, recurrence/new tumor, exenteration, locoregional and systemic melanoma-related metastasis, and melanoma-related death.

Purpose: To investigate risk factors for recurrent or new tumor in patients with conjunctival melanoma. Methods: Retrospective review of patients with conjunctival melanoma managed on the Ocular Oncology Service, Wills Eye Hospital from 1974 to 2019. Results: There were 540 patients with mean follow-up of 57.6 months, of whom 176 (33%) had recurrent or new tumor formation. Risk factors for recurrent or new tumor on univariate analysis included presentation at older age (OR: 1.02 [1.01–1.03] per 1-year increase in age, p = 0.002), history of prior conjunctival surgery (OR: 1.62 [1.05–2.49], p = 0.03), worse visual acuity at presentation (OR: 1.76 [1.04–2.98] per 1 log-unit increase, p = 0.04), more advanced AJCC clinical T-subcategory (OR: 1.08 [1.02–1.14] per 1 subcategory increase, p = 0.01), tumor primary location in tarsal conjunctiva (OR: 1.80 [1.09–2.98], p = 0.02), and secondary tumor involvement of the fornix (OR: 1.68 [1.06–2.65], p = 0.03), and eyelid (OR: 1.92 [1.07–3.43], p = 0.03). Risk factors on multivariate analysis using all demographics, clinical features, and tumor location included presentation at older age (OR: 1.02 [1.00–1.03], p = 0.01), history of prior conjunctival surgery (OR: 1.84 [1.16–2.94], p = 0.01), and more advanced AJCC clinical T-subcategory (OR: 1.07 [1.01–1.13] per one subcategory increase, p = 0.03). Conclusion: On multivariate analysis, the strongest predictors of recurrent or new tumor formation following treatment of conjunctival melanoma included older age, history of prior conjunctival surgery, and advanced AJCC T-subcategory. These results suggest that earlier detection and the first surgery in conjunctival melanoma management are critical for prevention of recurrent or new tumor, and we recommend prompt referral to an experienced surgeon.

To evaluate tumor control and globe salvage following intra-arterial chemotherapy (IAC) for retinoblastoma based on International Classification of Retinoblastoma (ICRB) and patient demographics.The medical records of 313 patients (341 eyes) treated with IAC were reviewed retrospectively. Chemotherapy agents included melphalan, topotecan, and carboplatin. Comparative analysis was performed for tumor control and globe salvage based on ICRB and patient demographics including age (≤12 vs 12 months), race (white vs nonwhite), and sex.Of the 341 eyes treated with 1,292 consecutive infusions of IAC as primary or secondary therapy for retinoblastoma, Kaplan-Meier 5-year estimates of globe salvage was 74%. Of those treated with IAC as primary therapy (n = 160 eyes; 655 infusions), 5-year globe salvage overall was 76%: and more specifically, 100% for groups B and C, 86% for group D, and 55% for group E. Of those treated with IAC as secondary therapy (n = 207 eyes; 859 infusions), 5-year globe salvage was 71%. Comparative analysis by race and sex demonstrated no differences in outcomes, but analysis by age revealed that younger patients had a higher rate of globe salvage (77% vs 72%; P 0.001). Complications (per catheterization) included retina ischemia (1%), choroidal ischemia (1%), neovascularization of the disk, retina, iris (NVI), glaucoma (about 1% each), and central/peripheral systemic ischemia (1%). Younger patients showed less NVI (P = 0.028), white patients showed less retinal ischemia (P = 0.037), and no difference by sex. There were no patients with metastatic disease or death.Our results suggest that IAC provides substantial tumor control for advanced and/or recurrent retinoblastoma with a high rate of globe salvage and few complications. There was little difference in outcomes per age, race, and sex.

Over the past two decades, we have witnessed the increasing use of photodynamic therapy (PDT) in the field of ocular oncology. Based on a review of the literature and our own experience, we herein review the role of PDT for the management of intraocular tumors. The discussion includes two main topics. First, we discuss the application of PDT for benign tumors, including circumscribed choroidal hemangioma, choroidal osteoma, retinal astrocytoma, retinal capillary hemangioma (retinal hemangioblastoma), and retinal vasoproliferative tumor. Second, we assess the role of PDT for malignant tumors, including choroidal melanoma and choroidal metastasis.

Purpose: To investigate the alterations in the retinal pigment epithelium (RPE) in the crest and trough portions of chorioretinal folds (CRFs) induced by an orbital vascular tumor. Methods: Review of multimodal imaging in two eyes of two patients with globe compression and CRFs from an orbital vascular tumor. Results: Fundus photography demonstrated obliquely extending CRFs with alternating hyperpigmented and hypopigmented linear alterations in both eyes. Fundus autofluorescence (AF) imaging showed obliquely oriented hypoAF lines, incompletely alternating with hyperAF lines. In Case 1, the hyperAF lines had interspersed hypoAF segments and Case 2 had peripapillary mottling of AF. Fluorescein angiography (FA) showed alternating hyper and hypofluorescent lines in the late phase in Case 1. Optical coherence tomography (OCT) documented relative thinning of RPE at the folded crests in Case 1 and preservation of RPE in Case 2. Swept-source OCT angiography (SS-OCTA) demonstrated oblique hyporeflective lines in the outer retina and choriocapillaris layers in Case 2. These findings suggest that the crest of a CRF represents thinned or rarified RPE with hypoAF, transmission hyperfluorescence (FA), partially attenuated RPE layer (OCT), and isoreflectivity (SS-OCTA) while the trough represents compressed RPE with irregular hyperAF, transmission hypofluorescence (FA), thickened RPE layer (OCT), and hyporeflectivity (SS-OCTA). Conclusion: The anatomic and functional status of the RPE in CRFs based on multimodal imaging reveals normal to attenuated RPE with hypofunctionality at the fold crest and compacted, thickened RPE at the trough with segmental functional impairment on AF imaging. Anatomic information regarding CRFs is evident on OCT, FA, and SS-OCTA while the functional status is depicted on AF.

Purpose To find immunohistochemical markers that distinguish adenocarcinoma of the nonpigmented ciliary epithelium (NPCE) from metastatic carcinoma, especially metastatic renal cell carcinoma. Design Retrospective case series. Methods Three cases of adenocarcinoma of the NPCE were examined histologically with hematoxylin-eosin stain and immunohistochemical stains including vimentin, AE1/AE3, Cam 5.2, CK7, PAX2, PAX8, AMACR, and CAIX. We also reviewed previously reported cases of this tumor. Results We found that the immunohistochemical profile of adenocarcinoma of the NPCE can overlap with renal cell carcinoma. Both tumors can express vimentin, cytokeratin AE1/AE3, Cam 5.2, PAX2, PAX8, and AMACR. One of the adenocarcinomas of the NPCE in our series also expressed CD10 and the renal cell carcinoma marker (RCC Ma). Carbonic anhydrase IX (CAIX) was not detected in any of the 3 tumors. Conclusions Adenocarcinomas arising in phthisic eyes can be diagnostically challenging. We have found it particularly difficult to distinguish adenocarcinoma of the NPCE from metastatic carcinoma, especially metastatic clear cell renal cell carcinoma and papillary renal cell carcinoma. Because of the immunophenotypic overlap, most patients will require systemic workup including imaging of the kidneys to be certain of the diagnosis.

Purpose To determine the usefulness of melan-A, SOX10, HMB45, and p16 immunohistochemical stains in the distinction between the low-grade and high-grade conjunctival melanocytic intraepithelial lesions, either independently or as components of an immunohistochemical panel. Design Retrospective observational case series. Methods Institutional pathology records between 2014 and 2018 were searched for all patients with conjunctival melanocytic intraepithelial lesions. Biopsies without supporting clinical history or tissue available for review and immunohistochemical analysis were excluded. Clinical, histopathologic, and immunohistochemical (p16, SOX10, HMB45, and Ki-67) findings were recorded. Results Thirty-one patients underwent 47 biopsies for conjunctival melanocytic lesions between 2014 and 2018. Pathologic diagnoses were low-grade conjunctival melanocytic intraepithelial lesion (n = 18, 38%) and high-grade conjunctival melanocytic intraepithelial lesion/melanoma in situ (n = 29, 62%). The addition of melan-A and SOX10 immunohistochemical stains resulted in an upgrade of conjunctival melanocytic intraepithelial lesion from low-grade to high-grade in 2 (4%) of 47 cases. The addition of melan-A and SOX10 immunohistochemical stains did not downgrade any of the histomorphologically high-grade lesions. In a clinical-pathologic multivariable model, the parameters most predictive of high-grade melanocytic intraepithelial lesion/melanoma in situ were involvement of the caruncle (odds ratio [OR] = 19, confidence interval [CI] 1.6-212; P = .02] and p16 cytoplasmic H-score >30 (OR = 81, CI 2.7 to >999; P = .01) Conclusion Although the stains for melanocytic markers melan-A and SOX10 facilitate assessment of melanocytic intraepithelial lesions, the current immunohistochemical panels have limited value in distinction between the low-grade and high-grade intraepithelial melanocytic proliferations and need to be used judiciously.

Purpose To evaluate the distribution of the PAX8 transcription factor protein in ocular tissues and to investigate if immunohistochemical stains for this biomarker are useful in the diagnosis of intraocular tumors. Design Observational case series. Participants Excision and cytologic analysis specimens of 6 ciliary body epithelial neoplasms, 2 iris epithelial neoplasms, 3 retinal pigment epithelial neoplasms, 3 intraocular medulloepitheliomas, 15 uveal melanomas, and 5 uveal melanocytomas. Methods Hematoxylin-eosin and PAX8 immunohistochemical stains were performed on all specimens. In appropriate cases, bleached preparations and other immunohistochemical stains, including AE1/AE3 cytokeratin, Lin28A, and CD45, were performed. Main outcome measures Distribution of PAX8 expression in normal and neoplastic tissue. Results Strong nuclear PAX8 expression was observed in the normal corneal epithelium, iris sphincter pupillae muscle, iris pigment epithelium and dilator muscle complex, nonpigmented and pigmented epithelia of the ciliary body, lens epithelium, and a subset of retinal neurons. The normal retinal pigment epithelium and uveal melanocytes did not stain for PAX8. The ciliary body epithelial and neuroepithelial tumors (adenoma, adenocarcinoma, and medulloepithelioma) showed uniform strong nuclear PAX8 immunoreactivity. All melanocytic tumors (iris melanoma, ciliary-choroidal melanoma, and melanocytoma) and retinal pigment epithelial neoplasms showed negative results for PAX8. A subset of tumor-associated lymphocytes, most prominent in uveal melanoma, showed positive results for PAX8. The uniformity of the PAX8 staining was superior to the variable cytokeratin staining in the ciliary epithelial neoplasms and the variable Lin28A staining in malignant medulloepithelioma. The veracity of PAX8 staining was equally as robust on cytologic analysis and open-flap biopsy specimens of ciliary epithelial and iris epithelial neoplasms, melanocytoma, and melanoma. Conclusions PAX8 has proven to be a very useful diagnostic marker in a select group of adult intraocular tumors, and we highly recommend its inclusion in diagnostic antibody panels of morphologically challenging intraocular neoplasms.

Purpose Birt-Hogg-Dube Syndrome (BHDS) is a rare autosomal dominant condition that can predispose patients to numerous cutaneous fibrofolliculomas and other cutaneous lesions, pulmonary cysts with spontaneous pneumothorax, and multifocal renal tumors and cancer. The genetic mutations responsible for BHDS are related to tumor suppression and the mammalian target of rapamycin (mTOR) pathway. Previous reports of the ocular findings in BHDS include eyelid fibrofolliculomas, "flecked chorioretinopathy," and one report of choroidal melanoma. We report a patient with BHDS who presented with choroidal melanoma, sector melanocytosis, and retinal pigment epithelial microdetachments. Methods Observational case report. Results A 38-year-old man with BHDS manifesting with facial fibrofolliculomas/tricodiscomas and pulmonary cysts with previous pneumothorax of both lungs was noted to have a large choroidal nevus, managed with observation elsewhere. On referral 1 year later, photopsia and visual field defect were noted, and the patient was discovered to have subtle patchy sector ocular melanocytosis of the iris and choroid with choroidal melanoma and dependent subretinal fluid. The melanoma measured 14 mm in basal dimension and 6.8 mm in thickness. In addition, pinpoint retinal pigment epithelial microdetachments were observed in both eyes at the equator and confirmed on optical coherence tomography. Custom-fit plaque radiotherapy was provided for tumor control. Conclusion The BHDS can be associated with tumors of the skin and kidney. In this case, we noted ocular melanocytosis, malignant choroidal melanoma, and bilateral pinpoint retinal pigment epithelial detachments.

Intraocular medulloepithelioma is a nonhereditary neoplasm of childhood arising from primitive medullary epithelium. It most often involves the ciliary body. Most patients present between 2 and 10 years of age with loss of vision, pain, leucocoria, or conjunctival congestion. The mass appears as a grey-white ciliary body lesion with intratumoral cysts. Presence of a neoplastic cyclitic membrane with extension to retrolental region is characteristic. Secondary manifestations like cataract and neovascular glaucoma may be present in up to 50% and 60% patients, respectively. These could be the first signs for which, unfortunately, about 50% patients undergo surgery before recognition of the hidden tumor. Systemic correlation with pleuropulmonary blastoma (DICER1 gene) has been documented in 5% cases. Histopathology shows primitive neuroepithelial cells arranged as cords closely resembling the primitive retina. Histopathologically, the tumor is classified as teratoid (containing heteroplastic elements) and nonteratoid (containing medullary epithelial elements), each of which are further subclassified as benign or malignant. Retinoblastoma-like and sarcoma-like areas may be seen within the tissue. The treatment modality depends on tumor size and extent of invasion. For small localized tumors (≤3-4 clock hours), conservative treatments with cryotherapy, plaque radiotherapy, or partial lamellar sclerouvectomy (PLSU) have been used. Plaque brachytherapy is generally preferred for best tumor control. Advanced and extensive tumors require enucleation. Rare use of intra-arterial and intravitreal chemotherapy has been employed. Systemic prognosis is favorable, but those with extraocular extension and orbital involvement show risk for local recurrence and metastatic disease, which can lead to death.

Purpose: The cancer genome atlas (TCGA) is a comprehensive project supported by the National Cancer Institute (NCI) in the United States to explore molecular alterations in cancer, including uveal melanoma (UM). This led to TCGA classification for UM. In this report, we review the American Joint Committee on Cancer (AJCC) classification and TCGA classification for UM from the NCI's Center for Cancer Genomics (NCI CCG) (based on enucleation specimens [n = 80 eyes]) and from Wills Eye Hospital (WEH) (based on fine needle aspiration biopsy [FNAB] specimens [n = 658 eyes]). We then compare accuracy and predictability of AJCC versus (vs.) TCGA. Methods: Review of published reports on AJCC and TCGA classification for UM was performed. Outcomes based on AJCC 7th and 8th editions were assessed. For TCGA, UM was classified based on chromosomes 3 and 8 findings including disomy 3 (D3), monosomy 3 (M3), disomy 8 (D8), 8q gain (8qG), or 8q gain multiple (8qGm) and combined into four classes including Class A (D3/D8), Class B (D3/8qG), Class C (M3/8qG), and Class D (M3/8qGm). Outcomes of metastasis and death were explored and a comparison (AJCC vs. TCGA) was performed. Results: In the NCI CCG study, there were 80 eyes with UM sampled by enucleation (n = 77), resection (n = 2), or orbitotomy (n = 1) and analysis revealed four distinct genetic classes. Metastasis and death outcomes were subsequently evaluated per class in the WEH study. The WEH study reviewed 658 eyes with UM, sampled by FNAB, and found Class A (n = 342, 52%), B (n = 91, 14%), C (n = 118, 18%), and D (n = 107, 16%). Comparison by increasing class (A vs. B vs. C vs. D) revealed older mean patient age (P < 0.001), worse entering visual acuity (P < 0.001), greater distance from the optic disc (P < 0.001), larger tumor diameter (P < 0.001), and greater tumor thickness (P < 0.001). Regarding outcomes, more advanced TCGA class demonstrated increased 5-year risk for metastasis (4% vs. 20% vs. 33% vs. 63%,P < 0.001) with corresponding increasing hazard ratio (HR) (1.0 vs. 4.1, 10.1, 30.0,P= 0.01 for B vs. A andP < 0.001 for C vs. A and D vs. A) as well as increased 5-year estimated risk for death (1% vs. 0% vs. 9% vs. 23%,P < 0.001) with corresponding increasing HR (1 vs. NA vs. 3.1 vs. 13.7,P= 0.11 for C vs. A andP < 0.001 for D vs. A). Comparison of AJCC to TCGA classification revealed TCGA was superior in prediction of metastasis and death from UM. Conclusion: TCGA classification for UM is simple, accurate, and highly predictive of melanoma-related metastasis and death, more so than the AJCC classification.

PURPOSE To evaluate spectral domain optical coherence tomography (SD-OCT) features of vitreoretinal lymphoma (VRL). METHODS Review of records and SD-OCT images of vitreoretinal lymphoma evaluated at Ocular Oncology Service, Wills Eye Hospital between July 1, 2000, and April 1, 2019. RESULTS There were 55 eyes of 32 patients included. At presentation, SD-OCT features included vitreous opacities (n = 36, 65%), preretinal deposits (n = 7, 13%), intraretinal deposits (n = 8, 15%), subretinal deposits (n = 20, 36%), retinal pigment epithelium abnormalities (n = 35, 64%), and subretinal pigment epithelium deposits (n = 35, 64%). Of 36 eyes with observed tumor progression, comparison (initial visit vs. time of progression) revealed more intraretinal deposits (17% vs. 50%, P = 0.005) at progression. Of 15 eyes with tumor recurrence, comparison (initial visit vs. time of recurrence) revealed more intraretinal deposits (7% vs. 47%, P = 0.04) at recurrence. At last visit, 39 eyes demonstrated tumor regression. By comparison (initial presentation vs. regression), there were less frequent vitreous opacities (67% vs. 0%, P < 0.001), intraretinal deposits (15% vs. 0%, P = 0.03), subretinal deposits (36% vs. 0%, P < 0.001), and subretinal pigment epithelium deposits (69% vs. 21%, P < 0.001) at regression. CONCLUSION Using SD-OCT in patients with vitreoretinal lymphoma, local tumor regression correlated with a reduction in vitreous opacities, intraretinal deposits, subretinal deposits, and subretinal pigment epithelium deposits. SD-OCT is useful in judging vitreoretinal lymphoma response to therapy.

We report a new observation of conjunctival intraepithelial neoplasia (CIN) in a young man following years of electronic cigarette use. A 22-year-old man with a 5-year electronic cigarette use (vaping) developed painless unilateral blurred vision in the right eye from mild superficial corneal opacification, unresponsive to topical antiviral therapy. Corneal scraping documented no infectious etiology. The abnormality persisted for 1 year and superficial keratectomy revealed high-grade CIN with enlarged pleomorphic and dyskeratotic cells. Interferon-alpha-2b was instituted. In this case, chronic exposure to electronic cigarette vapors (vaping) could have been associated with CIN in this young patient.

AimTo characterise combinations of multimodal imaging risk factors and predictive value for choroidal nevus transformation into melanoma.MethodsThis is a retrospective review of multimodal imaging features for 3806 choroidal nevi from 1 January 2007 through 1 January 2017. Kaplan-Meier estimates and Cox regression analyses were used to calculate 5-year percentages of growth to melanoma and HR.ResultsUsing multimodal imaging, six risk factors predictive of choroidal nevus transformation into melanoma were identified, namely tumour thickness >2 mm, subretinal fluid, symptoms of visual acuity loss to 20/50 or worse, orange pigment, hollow acoustic density and tumour largest basal diameter >5 mm. Kaplan-Meier 5-year estimated tumour growth was found in 1% of nevi with no risk factors, 11% (range 9%–37%) with one factor, 22% (12%–68%) with two factors, 34% (21%–100%) with three factors, 51% (0%–100%) with four factors and 55% (0%–100%) with five factors. HR for growth was 0.1 with no factor, 2.1–7.8 with one factor, 1.8–12.1 with two factors, 4.0–24.4 with three factors, 4.6–170.0 with four factors and 12.0–595.0 with five factors. The highest HR with each combination of two, three, four or five risk factors always included symptoms of visual acuity loss and orange pigment.ConclusionSix risk factors for choroidal nevus transformation into melanoma by multimodal imaging have been identified. Risk for transformation into melanoma is 1% when no factors are present, and approaches 100% with specific combinations of three or more risk factors. Understanding how combinations of factors influence risk of transformation into melanoma can guide counselling and treatment decisions.