Clinical Outcomes in Vitrectomized versus Non-vitrectomized Eyes in Patients with Primary Vitreoretinal Lymphoma.

AIM: To evaluate if there is a difference in the clinical course of primary vitreoretinal lymphoma (PVRL) in vitrectomized versus non-vitrectomized eyes. METHODS: Observational multicenter retrospective case series of patients diagnosed with PVRL between 2007 and 2019, at three tertiary centers. The main outcomes were relapse rates, inflammatory parameters, and best-corrected visual acuities (BCVA). Statistical methods used were an adjusted generalized estimating equation model, and a proportional Cox model. RESULTS: Eighty patients (150 eyes) were followed for a median of 1.7 years. At presentation, there were no clinical differences between the groups. The relapse rate was 0.091/eye-year (EY) for vitrectomized eyes and 0.087/EY for non-vitrectomized eyes (p = .35). Vitrectomized eyes had better BCVA than non-vitrectomized eyes (p < .001). CONCLUSIONS: Vitrectomy had no effect on the relapse rate in eyes with PVRL. However, the decrease in vitreous cell and debris led to vitrectomized eyes having better visual acuity than non-vitrectomized eyes.

Primary central nervous system lymphoma: Inter-compartmental progression.

There is limited understanding of the inter-compartmental progression and treatment outcomes of primary central nervous system lymphoma (PCNSL). In this multicenter retrospective cohort study on 234 patients with PCNSL (median age: 62.5 years [18-92]; median follow-up 35 months [0.1-237.0]) from 2000 till 2018 were divided into group 1 (ocular, 44 patients): 1A and 1B without and with CNS progression and group 2 (CNS, 190 patients): 2A and 2B without and with ocular progression, respectively. In group 1 (44 patients), 33 patients received local treatment, and 11 patients received systemic treatment. In group 2 (15 patients), six patients received combination treatment, while seven patients received only systemic treatment. A complete response was observed in 19 (43%) and 91 (48%) patients in groups 1 and 2, respectively. The 2-year progression-free survival (PFS) was 35% (95% CI: 0.23, 0.54) and 56% (95% CI: 0.49, 0.63) for groups 1 and 2, respectively (p < 0.0001). Age < 60 years was significantly associated with longer PFS (median PFS 48 vs. 24 months, p = 0.01). The overall survival (OS) at 2-year was similar among groups 1 and 2 (83% and 67%), respectively (p = 0.06). Thus, Initial compartment of involvement does not influence local response rate or OS.

Treatment of Aggressive Retinal Astrocytic Hamartoma with Oral Mechanistic Target of Rapamycin Inhibition.

PURPOSE: To describe the clinical course and outcomes of aggressive retinal astrocytic hamartoma (RAH) treated with oral mechanistic target of rapamycin inhibitors (mTORis). DESIGN: A retrospective clinical case series. PARTICIPANTS: Five patients with genetically confirmed tuberous sclerosis complex and visually significant RAH due to tumor growth or exudation. METHODS: In this retrospective clinical case series, a review of electronic medical records was performed to determine baseline and follow-up ophthalmic examination characteristics, along with ancillary imaging findings, in patients receiving off-label treatment with either oral sirolimus or everolimus for symptomatic RAH. MAIN OUTCOME MEASURES: Visual acuity, change in tumor size, degree of exudation, and adverse effects of the mTORis were evaluated. RESULTS: The 5 patients in this series ranged in age from 8 months to 54 years. Four were treated with sirolimus, and 1 received everolimus. In all the cases, the tumor height was stable or decreased after the treatment (median follow-up duration, 39 months; range, 11-73 months). Exudation improved after the treatment in all the cases. In an 8-month-old infant, frequent upper respiratory tract infections prompted the cessation of treatment. In 1 patient, the mTORi was temporarily withheld because of elevated liver enzyme levels. No other significant adverse effects were noted. CONCLUSIONS: Sirolimus and everolimus should be considered in the management of vision-threatening RAH, particularly in the setting of exudative and rapidly growing tumors. Four of the 5 patients in this series tolerated the oral mTORi and continued with the therapy. There were no serious complications.

Choroidal amelanotic tumours: clinical differentiation of benign from malignant lesions in 5586 cases.

PURPOSE: To investigate demographics and clinical features of patients with amelanotic choroidal tumours. DESIGN: Retrospective analysis. METHODS: Comparison of demographic and clinical features of various amelanotic choroidal tumours based on stratification by patient age, sex and tumour diameter. Included were all patients with amelanotic choroidal tumours evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA, over a 45-year time period. RESULTS: A total of 5586 amelanotic choroidal tumours in 4638 eyes of 4441 patients were included with a mean age at presentation of 58 years (median 60, range 0.1-100 years). Most patients were white (95%), female (56%) and with unilateral lesion (96%). By comparison, amelanotic melanoma presented at a younger mean age (57 years) compared with metastasis (60 years, p<0.001), nevus (61 years, p<0.001), lymphoma (65 years, p<0.001), sclerochoroidal calcification (70 years, p<0.001) and peripheral exudative haemorrhagic chorioretinopathy (80 years, p<0.001). Melanoma presented at an older mean age compared with osteoma (30 years, p<0.001), granuloma (42 years, p<0.001), haemangioma (49 years, p<0.001) and inflammatory choroidal lesions (49 years, p<0.001). Differences in race and sex were also seen between the various amelanotic choroidal lesions. With few exceptions, amelanotic melanoma had significantly larger basal diameter, greater thickness, more frequent association with subretinal fluid and more often ultrasonographically hollow, compared with other amelanotic choroidal lesions. CONCLUSION: Understanding the demographic and clinical features of amelanotic choroidal melanoma and other amelanotic lesions could lead to an earlier and more accurate diagnosis.

Visual Outcome at 4 Years Following Plaque Radiotherapy and Prophylactic Intravitreal Bevacizumab (Every 4 Months for 2 Years) for Uveal Melanoma: Comparison With Nonrandomized Historical Control Individuals.

Importance: Radiation retinopathy following plaque radiotherapy for uveal melanoma can lead to vision loss that might be avoided with prophylactic anti-vascular endothelial growth factor treatment. Objective: To determine visual outcome following prophylactic intravitreal bevacizumab in patients with plaque-irradiated uveal melanoma. Design, Setting, and Participants: Retrospective, nonrandomized, interventional cohort study at Wills Eye Hospital, Philadelphia, Pennsylvania. Prophylactic bevacizumab was administered between 2008 and 2018 to 1131 eyes with irradiated uveal melanoma (bevacizumab group) and compared with 117 eyes with irradiated uveal melanoma between 2007 and 2009 (no bevacizumab [historical control] group). Interventions: Prophylactic intravitreal bevacizumab was provided at the time of plaque removal as well as 6 subsequent injections at 4-month intervals over 2 years. Main Outcomes and Measures: Visual acuity. Results: The median patient age was 61 years, 1195 of 1248 patients were white (96%), and 632 of 1248 were women (51%). The median tumor thickness was 4.0 mm, and median distance to foveola was 3.0 mm. A difference was not identified (bevacizumab vs control group) in demographic features, clinical features, or radiation parameters. The mean follow-up was 40 months vs 56 months (mean difference, -18; 95% CI, -24 to -13; P < .001). By survival analysis, the bevacizumab group demonstrated less optical coherence tomography evidence of cystoid macular edema at 24 months (28% vs 37%; hazard ratio [HR], 1.5; 95% CI, 1.1-2.2; P = .02) and 36 months (44% vs 54%; HR, 1.5; 95% CI, 1.1-2.1; P = .01), less clinical evidence of radiation maculopathy at 24 months (27% vs 36%; HR, 1.5; 95% CI, 1.0-2.2; P = .03), 36 months (44% vs 55%; HR, 1.50; 95% CI, 1.1-2.0; P = .01), and 48 months (61% vs 66%; HR, 1.4; 95% CI, 1.0-1.9; P = .03), and less clinical evidence of radiation papillopathy at 18 months (6% vs 12%; HR, 2.0; 95% CI, 1.1-3.9; P = .04). Nonparametric analysis documented better visual acuity outcomes in the bevacizumab group at all points, including 12 months (median logMAR visual acuity [Snellen equivalent]: 0.30 [20/40] vs 0.48 [20/60]; mean difference, -0.28; 95% CI, -0.48 to -0.07; P = .02), 24 months (0.40 [20/50] vs 0.70 [20/100]; mean difference, -0.52; 95% CI, -0.75 to -0.29; P < .001), 36 months (0.48 [20/60] vs 1.00 [20/200]; mean difference, -0.49; 95% CI, -0.76 to -0.21; P = .003), and 48 months (0.54 [20/70] vs 2.00 [counting fingers]; mean difference, -0.71; 95% CI, -1.03 to -0.38; P < .001). Conclusions and Relevance: These findings from a retrospective cohort of plaque radiotherapy and prophylactic intravitreal bevacizumab in patients with uveal melanoma suggest better visual outcomes when compared with nonrandomized historical control individuals through 4 years.

Uveal metastasis in 1111 patients: Interval to metastasis and overall survival based on timing of primary cancer 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 < 0.001), breast (6.5 years, p < 0.001), and thyroid (13 years, p < 0.001). By Kaplan-Meier analysis, the 5-year overall survival showed no difference between patients with primary cancer found before (28%) vs after (20%) vs never found (33%), relative to uveal metastasis. CONCLUSION: Of 1111 patients with uveal metastasis, early-onset uveal metastases were found with lung and gastrointestinal tract cancers, whereas late-onset metastases were found with breast and thyroid cancers. Overall survival did not vary on whether the primary tumor was diagnosed before, after, or never found, relative to uveal metastasis.

Uveal Metastasis: Clinical Features and Survival Outcome of 2214 Tumors in 1111 Patients Based on Primary Tumor Origin.

PURPOSE: The purpose of this study is to evaluate patients with uveal metastasis based on primary tumor site. METHODS: Retrospective analysis from Wills Eye Hospital, Philadelphia, PA, USA, for uveal metastasis clinical features and outcomes based on the primary tumor site. RESULTS: There were 2214 uveal metastases diagnosed in 1111 consecutive patients. The demographics included mean age of 60 years (median 61 years), Caucasian race (88%), and female gender (64%). The tumor was unilateral (82%) and primary site was established before uveal metastasis (67%). The primary tumor originated in the breast (37%), lung (26%), kidney (4%), gastrointestinal (GI) tract (4%), cutaneous melanoma (2%), lung carcinoid (2%), prostate (2%), thyroid (1%), pancreas (1%), other sites (3%), and unknown (16%). Comparative analysis of the 5 most common primary sites (breast, lung, kidney, GI tract, and cutaneous melanoma), revealed metastasis at mean age (57, 62, 66, 61, 59 years), as unilateral tumor (74%, 86%, 85%, 93%, 85%), with mean number of metastasis/eye (1.9, 1.7, 1.0, 1.1, 2.0), and in females (99%, 46%, 26%, 25%, 30%). Choroidal metastases measured mean base (9.3, 10.2, 9.1, 11.0, 7.3 mm), mean thickness (2.4, 3.6, 4.4, 4.0, 2.9 mm), and demonstrated predominant color yellow (94%, 91%, 56%, 97%, 36%). Of the 769 patients with documented follow-up, mean patient survival was poor (22.2, 11.5, 8.6, 12.4, 11.4 months) and Kaplan-Meier analysis revealed 3-year survival (33%, 19%, 0%, 14%, 21%) and 5-year survival (24%, 13%, 0%, 14%, 21%). The worst survival was found in patients with pancreatic metastasis (mean 4.2 months) and best survival with lung carcinoid (92% at 5 years). CONCLUSION: In a tertiary referral service, uveal metastasis originates from cancer in the breast, lung, kidney, GI tract, cutaneous melanoma, or others. Overall prognosis is poor with 5-year survival at 23% and worst survival with pancreatic metastasis whereas best survival with lung carcinoid metastasis.