Pushing the limit: Globe salvage of Group D retinoblastoma with severe vitreous seeding with intra-arterial chemotherapy and 15 cycles of intravitreal chemotherapy.

Purpose: To report the successful treatment of persistent retinoblastoma vitreous seeding with 6 cycles of intra-arterial chemotherapy and 15 cycles of intravitreal chemotherapy injections. Observations: A three-year-old female presented to the ocular oncology clinic with Group D retinoblastoma with severe vitreous seeding. The patient received 3 cycles of intra-arterial chemotherapy (melphalan, topotecan, and carboplatin) and 15 cycles of intravitreal chemotherapy (melphalan and combined melphalan/topotecan). Complete tumor regression and resolution of vitreous seeding was achieved. The best corrected visual acuity in the affected eye was 20/50. Conclusions and Importance: Intravitreal chemotherapy for retinoblastoma vitreous seeding is often restricted to 8 treatment cycles. Patients who do not respond after 8 cycles face salvage therapy with radiation or enucleation. This is a case in which prolonged intravitreal chemotherapy delivery was well tolerated and resulted in sustained tumor remission, with useful visual acuity in the treated eye.

METformin for the MINimization of Geographic Atrophy Progression (METforMIN): A Randomized Trial.

Purpose: Metformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in observational studies. We aimed to evaluate the efficacy of oral metformin for slowing geographic atrophy (GA) progression. Design: Parallel-group, multicenter, randomized phase II clinical trial. Participants: Participants aged ≥ 55 years without diabetes who had GA from atrophic AMD in ≥ 1 eye. Methods: We enrolled participants across 12 clinical centers and randomized participants in a 1:1 ratio to receive oral metformin (2000 mg daily) or observation for 18 months. Fundus autofluorescence imaging was obtained at baseline and every 6 months. Main Outcome Measures: The primary efficacy endpoint was the annualized enlargement rate of the square root-transformed GA area. Secondary endpoints included best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit. Results: Of 66 enrolled participants, 34 (57 eyes) were randomized to the observation group and 32 (53 eyes) were randomized to the treatment group. The median follow-up duration was 13.9 and 12.6 months in the observation and metformin groups, respectively. The mean ± standard error annualized enlargement rate of square root transformed GA area was 0.35 ± 0.04 mm/year in the observation group and 0.42 ± 0.04 mm/year in the treatment group (risk difference = 0.07 mm/year, 95% confidence interval = -0.05 to 0.18 mm/year; P = 0.26). The mean ± standard error decline in BCVA was 4.8 ± 1.7 letters/year in the observation group and 3.4 ± 1.1 letters/year in the treatment group (P = 0.56). The mean ± standard error decline in LLVA was 7.3 ± 2.5 letters/year in the observation group and 0.8 ± 2.2 letters/year in the treatment group (P = 0.06). Fourteen participants in the metformin group experienced nonserious adverse events related to metformin, with gastrointestinal side effects as the most common. No serious adverse events were attributed to metformin. Conclusions: The results of this trial as conducted do not support oral metformin having effects on reducing the progression of GA. Additional placebo-controlled trials are needed to explore the role of metformin for AMD, especially for earlier stages of the disease. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.