Immunosuppressive therapy for Vogt-Koyanagi-Harada disease: a retrospective study and review of literature.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is an idiopathic autoimmune disease which targets melanin-containing tissues such as the uvea, meninges, ear and skin. This typically presents in the eye with acute findings of granulomatous anterior uveitis, diffuse choroidal thickening, multiple focal areas of sub-retinal fluid and, in severe cases, optic nerve involvement with bullous serous retinal detachment can occur. Early initiation of treatment has been advocated to prevent progression to the chronic stage of the disease, which can result to a sunset glow fundus with devastatingly poor visual outcome. Treatment is usually initiated with corticosteroids followed by an early introduction of immunosuppressive treatment (IMT) to achieve immediate response after disease presentation, although the choice of IMT for VKH can vary. MAIN FINDINGS: We conducted a retrospective case-series to investigate the management trend of treating VKH over a 20-year period. Twenty-six patients were included and we found a shift from steroid monotherapy to combined IMT/low-dose steroid for the management of acute initial-onset of VKH in the last 10 years. Our average time from diagnosis to initiation of IMT was 2.1 months. 81% (21 of 26 patients) of our patients treated with combined IMT/steroid were able to achieve disease stability with significant good visual outcome at 24 months (Median VApre-IMT = 0.3 Logmar vs VApost-IMT = 0.0 Logmar, p = 0.0001). MMF monotherapy was the most common IMT used and it was well-tolerated by our patients. Even so, 50% of our patients who were treated with MMF did not achieve disease control. We then performed a literature review to identify any IMT which could be superior in the treatment of VKH. We also share our experience (where applicable) on the various treatment options found from the literature review. SHORT CONCLUSION: Our study found that patients with VKH who were treated with combined IMT/low-dose steroids achieved significantly better visual improvement at 24 months compared to steroid monotherapy. We frequently chose MMF and this appears to be well tolerated by our patients. Since its introduction, anti-TNF agents are increasingly becoming a popular choice of treatment for VKH as these have been shown to be safe and effective. However, more data is required to provide evidence that anti-TNF agents can be used as first-line treatment and as monotherapy.

Macula-predominant retinopathy associated with biallelic variants in RDH12.

PURPOSE: To describe the clinical, electrophysiological, and molecular features of an unusual macula-predominant retinopathy in two unrelated probands with biallelic variants in RDH12. METHODS: Retrospective case series. RESULTS: A 29-year-old female presented with visual loss since the age of 14 years. Retinal examination revealed symmetric outer retinal atrophy in the posterior pole with peripapillary sparing. Fundus autofluorescence (AF) showed patchy loss of AF in the posterior pole, with hyper-autofluorescent borders. Optical coherence tomography (OCT) showed loss of the macular outer retinal layers. Pattern electroretinography (PERG) showed macular dysfunction and full-field ERG indicated mild loss of photoreceptor function. Next-generation sequencing (NGS) identified two variants in RDH12: p.(Arg234His) and c.448 + 1 G > A in trans. The second patient was a 10-year-old male with bilateral macular changes and visual loss. Retinal examination showed bilateral macular cloverleaf-like outer retinal changes, with relative foveal sparing. Fundus AF showed bilateral macular hypo-autofluorescent patches with a border of increased signal and preserved foveal AF. OCT showed attenuation of the perifoveal outer retinal layers in the regions of reduced AF signal. PERG showed macular dysfunction, but the full-field ERG was normal. NGS and whole-genome sequencing identified two variants in RDH12: p.(Arg234His) and p.(Cys245_Leu247deI) in trans. CONCLUSIONS: Disease-causing variants in RDH12 are typically associated with early-onset severe retinal dystrophy with significant macular involvement. Hypomorphic alleles of this gene cause relatively mild retinopathy with predominant macular involvement. This phenotype demonstrates the vulnerability of the macular photoreceptors to certain perturbations of RDH12.

Effects of Dietary Supplementation with Sea Buckthorn (Hippophae rhamnoides L.) Seed Oil on an Experimental Model of Hypertensive Retinopathy in Wistar Rats.

BACKGROUND/AIMS: Sea buckthorn (Hippophae rhamnoides L.) oil is a rich source of phytosterols, flavonoids, unsaturated fatty acids, and carotenoids, known for their antioxidant and neuroprotective activity. In this study, we investigated the neuroprotective and antioxidant effect of sea buckthorn oil on rat retina in hypertensive retinopathy. METHODS: Twenty-eight male 6-month-old Wistar rats were separated into 3 groups: (1) controls, (2) unilateral nephrectomized rats receiving drinking water with 1% NaCl, (3) unilateral nephrectomized rats receiving 0.5 mL sea buckthorn oil and drinking water with 1% NaCl. Systemic pressures were being measured with the tail-cuff method. The antiapoptotic effect of sea buckthorn was determined by measuring glial fibrillary acidic protein (GFAP), cleaved caspase-3, and glutamine synthetase levels with immunohistochemistry and Western blot. RESULTS: Nephrectomy and salt intake caused increases in both systolic and diastolic pressures. Both types of analysis showed that group 2 had statistically significant increases in the expression of GFAP and cleaved caspase-3, while group 3 showed no significant differences compared with the control group. The expression of glutamine synthetase showed no significant differences between the 3 groups. CONCLUSIONS: Our findings suggest that sea buckthorn could notably protect the retina from damage induced by hypertensive retinopathy.