Shields, Jerry A.

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.

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.

AbstractImportanceThe impact of tumour thickness on radiation complications following plaque radiotherapy for uveal melanoma in the anti‐vascular endothelial growth factor (VEGF) era remains unknown.BackgroundTo evaluate treatment outcomes following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma based on initial tumour thickness.DesignThis was a retrospective, interventional case series.ParticipantsPatients with uveal melanoma were included in this study.MethodsA 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 measuresRadiation‐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 [<3.0 mm] vs medium [3.1‐8.0 mm] vs large [>8.0 mm]).ResultsOf 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 < .001), earlier onset of CME (33 vs 26 vs 19 months, P < .001) and greater development of NVI (<1% vs 2% vs 13%, P < .001) and NVG (1% vs 2% vs 12%, P < .001). Radiation‐induced maculopathy, papillopathy and retinopathy were not associated with tumour thickness.Conclusions and relevanceCompared with small and medium uveal melanoma, large uveal melanoma demonstrated greater 48‐month risk for CME, shorter time to CME onset and greater development of NVI and NVG following plaque radiotherapy and prophylactic intravitreal bevacizumab.

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 review immune checkpoint inhibitor indications and ophthalmic side effects. Methods: A literature review was performed using a PubMed search for publications between 1990 and 2017. Results: Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1–24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. Conclusion: Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.