Retinoblastoma, the most common eye cancer of childhood, is fatal if left untreated. Prognosis of patients with retinoblastoma in high-income countries (HICs) has improved over the past 50 years, now reaching a near 100% disease-free survival rate.^1-3 This is attributed to several factors, including (1) creation of specialized referral centers, (2) decoding of the genetic basis of the disease, (3) formation of screening programs, and (4) the introduction of chemotherapy.⁴ In HICs, retinoblastoma is a curable disease, and attention has now shifted to eye salvage^5,6 and improvement of quality of life.⁷ In low- and middle-income countries (LMICs), where more than 80% of global retinoblastoma cases arise, the prognosis is poor, and it is assumed that this is because of delayed diagnosis and treatment.^8-10 Publications from LMICs are scarce, and many countries do not report their retinoblastoma data.¹¹ The stage of retinoblastoma at the time of diagnosis in low-income, middle-income, and high-income countries has not been surveyed globally. This information is important for policy and health care planning at national and international levels.

Background: Graves’ ophthalmopathy (GO) is a common cause of morbidity in patients with Graves’ disease. Optimal treatment of GO remains unclear, and an evidence-based approach may improve patients’ outcome. Methods: A systematic review and metaanalysis of randomized, controlled trials comparing treatment modalities for GO vs. placebo, no intervention, or other treatments. Primary outcome was the clinical activity score (CAS). Results: Thirty-three trials evaluating 1367 patients fulfilled inclusion criteria. In patients with moderate to severe GO, iv pulse corticosteroids were significantly better than oral corticosteroids in reducing CAS [standardized mean difference −0.64, 95% confidence interval (CI) −1.11 to −0.17, χ² 7.91, I² 62%, random effect], with lower rate of adverse events. Somatostatin analogs showed a minor but statistically significant advantage over placebo (mean difference −0.63, 95% CI −0.98 to −0.28). There was no advantage of orbital radiotherapy over sham radiation in CAS, but radiotherapy was superior for response rates of diplopia (odds ratio 4.88, 95% CI 1.93–12.34, two trials). Treatment with combination of orbital radiotherapy and corticosteroids was significantly better than with either treatment alone (standardized mean difference −1.05, 95% CI −1.62 to −0.48). Conclusions: Current evidence demonstrates the efficacy of iv corticosteroids in decreasing CAS in patients with moderate to severe GO. Intravenous pulse corticosteroids therapy has a small but statistically significant advantage oral therapy and causes significantly fewer adverse events. Somatostatin analogs have marginal clinical efficacy. The efficacy of orbital radiotherapy as single therapy remains unclear, whereas the combination of radiotherapy with corticosteroids has better efficacy than either radiotherapy or oral corticosteroids alone.

Metastases to the eye are usually detected in the choroid (88%), iris (9%), or ciliary body (2%), and, rarely, in the retina (<1%).^1-3 Retinal metastases caused by systemic cancers have been documented in case reports,^4-19 but, owing to the infrequency of this finding, there has not been extensive experience at any single ocular oncology center. In this article, we examine our 40-year experience treating patients with retinal metastasis. During this time, we have treated several thousand patients with uveal metastasis and hundreds with orbital metastasis but only a few with retinal metastasis. We document the clinical features, treatment, and outcomes of patients with retinal metastasis.

Background: Uveitis consists of a spectrum of inflammatory disorders characterized by ocular inflammation. The underlying pathophysiology consists of a complex interplay of various inflammatory pathways. Interleukin 6 is an important mediator of inflammation in uveitis and constitutes focus of research toward development of newer biological therapies in the management of non-infectious uveitis.Main body: Pan-blockade of the inflammatory pathways with steroids is generally the first step in the management of acute non-infectious uveitis. However, long-term therapy with steroids is associated with systemic and ocular side effects, thereby necessitating the need for development of steroid sparing agents. IL-6 is a cytokine produced by various immune cells, in response to molecular patterns and affects multiple inflammatory cells. In particular, IL-6 is involved in differentiation of CD-4 cells into Th-17 cells that have been shown to play a significant role in various immune-mediated diseases such as uveitis. This broad-spectrum immunomodulatory activity makes IL-6 an excellent target for immunomodulatory therapy. Tocilizumab was the first IL-6 inhibitor to demonstrate efficacy in humans. It inhibits IL-6 from binding to both membrane-bound and soluble receptor and can be administered via intravenous (IV) and subcutaneous (SC) routes. It has been FDA approved for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Following the approval in systemic diseases, its efficacy was demonstrated in various uveitis studies including a phase 2 clinical trial (STOP-Uveitis). Overall, tocilizumab has shown a good safety profile with the risk of malignancy consistent with that expected in patients with rheumatoid arthritis. However, tocilizumab therapy has been shown to increase the risk for gastrointestinal perforation and dose-dependent neutropenia. Following the success of tocilizumab, several other agents targeting the IL-6 pathway are in the pipeline. These include sirukumab, siltuximab, olokizumab, clazakizumab, and EBI-031 which target IL-6; Sarilumab and ALX-0061 act on the IL-6 receptor.Conclusion: Studies have shown that IL-6 inhibitors can be effective in the management of NIU. In addition, the levels of IL-6 are elevated in other ocular vascular diseases such as retinal vein occlusion and diabetic macular edema. The roles of IL-6 inhibition may be broadened in the future to include the management of retinal vascular diseases and non-uveitic macular edema.