Reappraisal of the management of Vogt-Koyanagi-Harada disease: sunset glow fundus is no more a fatality.

Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis. Aim of the study was to gather a body of evidence from the literature and from experts that systemic corticosteroid combined with non-steroidal immunosuppressive therapy should become the standard of care in initial-onset VKH disease. Literature was reviewed and leading experts in VKH were consulted in different parts of the world in order to put forward a consensus attitude in the management of initial-onset VKH disease. There was a substantial body of evidence in the literature that early aggressive and sustained corticosteroid and non-steroidal immunosuppressive therapy in initial-onset VKH disease allows to achieve full control of choroidal inflammation, eliminating any subclinical choroidal inflammation, and substantially reduces recurrences with improvement of anatomical and functional outcomes. This was in agreement with experts' opinion and practice. ICGA was the method of choice to monitor disease evolution. Since the choroidal space is easily accessible to systemic therapy and because inflammation in VKH disease is exclusively originating from the choroidal stroma, early and sustained treatment right at the onset of the disease process with dual corticosteroid and non-steroidal immunosuppressive therapy can result in full "healing" in many cases preventing sunset glow fundus which results from depigmentation from chronic uncontrolled inflammation

Catching the therapeutic window of opportunity in early initial-onset Vogt�Koyanagi�Harada uveitis can cure the disease

Purpose: Vogt�Koyanagi�Harada (VKH) disease is a primary autoimmune granulomatous choroiditis that begins in the choroidal stroma. The aim of this review was to gather a body of evidence for the concept of a window of therapeutic opportunity, defined as a time interval following initial-onset disease during which adequate treatment will substantially modify the disease outcome and possibly even lead to cure, similar to what has been described for rheumatoid arthritis. Methods: We reviewed the literature and consulted leading experts in VKH disease to determine the consensus for the notion of a therapeutic window of opportunity in VKH disease. Results: We found a substantial body of evidence in the literature that a therapeutic window of opportunity exists for initial-onset acute uveitis associated with VKH disease. The disease outcome can be substantially improved if dual systemic steroidal and non-steroidal immunosuppressants are given within 2�3 weeks of the onset of initial VKH disease, avoiding evolution to chronic disease and development of �sunset glow fundus.� Several studies additionally report series in which the disease could be cured, using such an approach. Conclusions: There is substantial evidence for a therapeutic window of opportunity in initial-onset acute VKH disease. Timely and adequate treatment led to substantial improvement of disease outcome and prevented chronic evolution and �sunset glow fundus,� and very early treatment led to the cure after discontinuation of therapy in several series, likely due to the fact that the choroid is the sole origin of inflammation in VKH disease. © 2018 The Author(s

Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic environment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106882/1/nyas12412.pd

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Indocyanine green angiographic findings in initial-onset acute Vogt-Koyanagi-Harada disease.

To study the features of Indocyanine green angiography (ICGA) in patients with initial-onset acute Vogt-Koyanagi-Harada (VKH) disease. Retrospective cohort study of ICGA performed with the use of Heidelberg scanning laser ophthalmoscope on a consecutive series of patients with initial-onset acute VKH disease. The following signs were analysed: choroidal perfusion inhomogeneity, early hyperfluorescent stromal vessels, hypofluorescent dark dots (HDDs), fuzzy or lost pattern of large stromal choroidal vessels, disc hyperfluorescence, and, diffuse late choroidal hyperfluorescence. In addition, we looked for any new ICGA findings. Thirty-six patients (72 eyes) from a single academic institution were studied. The following findings were identified: HDDs in all eyes (100%), fuzzy or lost pattern of large stromal vessels in all eyes (100%), early hyperfluorescent stromal vessels were seen in 60 eyes (83%), diffuse late choroidal hyperfluorescence was present in 51 eyes (71%), choroidal perfusion inhomogeneity was seen in 44 eyes (61%), disc hyperfluorescence was seen in 25 cases (69%), and choroidal folds were present in only six eyes. New ICGA findings detected in this study were hypofluorescent patches corresponding to areas of exudative retinal detachment in 60 eyes (83%) and 'starry sky' pattern of late widespread punctate choroidal hyperfluorescence in 37 eyes (51%). The most prevalent ICGA findings were HDDs, fuzzy stromal vessels and early hyperfluorescent stromal vessels in patients with initial-onset acute VKH disease. Novel ICGA findings in this group of patients included hypofluorescent patches corresponding to areas of exudative retinal detachment, and late widespread punctate choroidal hyperfluorescence taking on a 'starry sky' pattern

Vogt-Koyanagi-Harada disease: recurrence rates after initial-onset disease differ according to treatment modality and geographic area.

Background/Purpose Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis producing a spill-over panuveitis. For initial-onset VKH disease, it is increasingly thought that corticosteroid therapy is not sufficient and additional non-steroidal immunosuppressive therapy is needed. At the 11th workshop on VKH, the disease was said to be well controlled with corticosteroids alone in Japanese patients. The aim of this study was to review the literature to determine whether different levels of severity exist in different geographical areas. Literature was reviewed for studies on the evolution of initial-onset VKH disease, looking at treatment modalities and proportion of cases with chronic evolution and/or sunset-glow fundus (SGF). PubMed search yielded 1249 references containing the term of Vogt-Koyanagi-Harada. Twenty references (15 from outside of Japan and 5 from Japan) contained information on the evolution of treated initial-onset disease. For the "international" group, percentage of chronic evolution after systemic corticosteroid monotherapy was 61%, and after combined steroidal and non-steroidal therapy it fell to 2% (0% in 3/4 studies). In the Japanese studies where all patients received systemic corticosteroids alone, chronic evolution was reported in 25%; however, SGF amounted to 61%. In the world at large, chronic evolution of initial-onset VKH disease treated with corticosteroids alone concerned two-thirds of patients. Japanese studies showed that chronic evolution was substantially less frequent, indicating possibly less severe disease in Japan. This proportion fell to almost zero when dual steroidal and non-steroidal immunosuppression was given at onset