COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity-including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others-must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease.Ophthalmic researc

Evolving consensus for immunomodulatory therapy in non-infectious uveitis during the COVID-19 pandemic

Background Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the concerns related to IMT and the increased risk of infections, an urgent need for guidance on the management of IMT in patients with uveitis has emerged. Methods A cross-sectional survey of international uveitis experts was conducted. An expert steering committee identified clinical questions on the use of IMT in patients with NIU during the COVID-19 pandemic. Using an interactive online questionnaire, guided by background experience and knowledge, 139 global uveitis experts generated consensus statements for IMT. In total, 216 statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents and biologics in patients with NIU. Thirty-one additional questions were added, related to general recommendations, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine. Results Highest consensus was achieved for not initiating IMT in patients who have suspected or confirmed COVID-19, and for using local over systemic corticosteroid therapy in patients who are at high-risk and very high-risk for severe or fatal COVID-19. While there was a consensus in starting or initiating NSAIDs for the treatment of scleritis in healthy patients, there was no consensus in starting hydroxychloroquine in any risk groups. Conclusion Consensus guidelines were proposed based on global expert opinion and practical experience to bridge the gap between clinical needs and the absence of medical evidence, to guide the treatment of patients with NIU during the COVID-19 pandemic.Ophthalmic researc

Research priorities in prehabilitation for patients undergoing cancer surgery: an international Delphi study

Background Recently, the number of prehabilitation trials has increased significantly. The identification of key research priorities is vital in guiding future research directions. Thus, the aim of this collaborative study was to define key research priorities in prehabilitation for patients undergoing cancer surgery. Methods The Delphi methodology was implemented over three rounds of surveys distributed to prehabilitation experts from across multiple specialties, tumour streams and countries via a secure online platform. In the first round, participants were asked to provide baseline demographics and to identify five top prehabilitation research priorities. In successive rounds, participants were asked to rank research priorities on a 5-point Likert scale. Consensus was considered if > 70% of participants indicated agreement on each research priority. Results A total of 165 prehabilitation experts participated, including medical doctors, physiotherapists, dieticians, nurses, and academics across four continents. The first round identified 446 research priorities, collated within 75 unique research questions. Over two successive rounds, a list of 10 research priorities reached international consensus of importance. These included the efficacy of prehabilitation on varied postoperative outcomes, benefit to specific patient groups, ideal programme composition, cost efficacy, enhancing compliance and adherence, effect during neoadjuvant therapies, and modes of delivery. Conclusions This collaborative international study identified the top 10 research priorities in prehabilitation for patients undergoing cancer surgery. The identified priorities inform research strategies, provide future directions for prehabilitation research, support resource allocation and enhance the prehabilitation evidence base in cancer patients undergoing surgery

Bringing antigens to attention: a conspiracy of genes, proteins and cells

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Current ophthalmology practice patterns for syphilitic uveitis.

Syphilitic uveitis is re-emerging alongside the systemic infection. In July 2017, an international group of uveitis-specialised ophthalmologists formed the International Ocular Syphilis Study Group to define current practice patterns. 103 Study Group members based in 35 countries completed a 25-item questionnaire focused on case load, clinical presentations, use and interpretation of investigations, treatment and clinical indicators of poor prognosis. Members managed a mean of 6.1 patients with syphilitic uveitis in clinics that averaged 707 annual cases of uveitis (0.9%); 53.2% reported increasing numbers over the past decade. Patients presented to more members (40.2%) during secondary syphilis. Uveitis was usually posterior (60.8%) or pan (22.5%); complications included optic neuropathy, macular oedema and posterior synechiae. All members diagnosed syphilitic uveitis using serological tests (simultaneous or sequential testing algorithms), and 97.0% routinely checked for HIV co-infection. Cerebrospinal fluid (CSF) analysis was ordered by 90.2% of members, and 92.7% took uveitis plus Venereal Disease Research Laboratory test (VDRL) or fluorescent treponemal antibody absorption test (FTA-ABS) to indicate neurosyphilis. Patients were commonly co-managed with infectious disease physicians, and treated with penicillin for at least 10-14 days, plus corticosteroid. Features predicting poor outcome included optic neuropathy (86.3%) and initial misdiagnosis (63.7%). Reasons for delayed diagnosis were often practitioner-related. 82.5% of members tested every patient they managed with uveitis for syphilis. This comprehensive report by an international group of uveitis-specialised ophthalmologists provides a current approach for the management of syphilitic uveitis

The role of melanocytes in the human choroidal microenvironment and inflammation: Insights from the transcriptome

The choroid within the human eye contains a rich milieu of cells including melanocytes. Human choroidal melanocytes (HCMs) absorb light, regulate free radical production, and were recently shown to modulate inflammation. This study aimed to identify key genes and pathways involved in the inflammatory response of HCMs through the use of RNA-seq. Primary HCMs were cultured from donor choroids, RNA was extracted from control and lipopolysaccharide (LPS)-treated HCMs, and mRNA was sequenced. Functional annotation and pathway analysis were performed using gene ontology and gene set enrichment analyses. Representative RNA-seq results were verified with RT-qPCR and protein measurements. We detected 100 differentially expressed genes including an array of CCL and CXCL cytokines and mediators of cell-cell and cell-matrix adhesion, such as ICAM1, CLDN1, CCN3, ITGA1 and ITGA11. Functional annotation showed that these gene sets control inflammatory pathways, immune cell trafficking, cell-cell adhesion, interactions with the extracellular matrix and blood vessels, angiogenesis and epithelial-to-mesenchymal transitions. Our study provides insights into the transcriptional regulation of primary HCMs in response to inflammatory stimuli and identifies novel melanocyte-driven mechanisms potentially involved in choroidal homeostasis and inflammation.Ophthalmic researc

Twenty-four-month outcomes of inflammatory choroidal neovascularisation treated with intravitreal anti-vascular endothelial growth factors: a comparison between two treatment regimens

Background and aim: There is still no established treatment regimen for eyes with inflammatory choroidal neovascularisation (iCNV) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections. This study compared the 24-month outcomes of two treatment regimens of anti-VEGF injections in eyes with iCNV. Methods: Eyes with iCNV treated with anti-VEGF injections were divided into two groups: eyes treated with a loading phase of 3 monthly injections and then re-treated as needed (LOADING group) and eyes treated as needed from the beginning (PRN group). Visual acuity (VA), number of injections and iCNV recurrences at 24 months were compared between the groups. Results: Eighty-two eyes were included, 42 in the LOADING and 40 in the PRN group. Baseline VA (mean(SD)) was 72.3 (15.8) letters in the LOADING vs 75.7 (15.6) letters in the PRN group (p=0.32). The VA (mean (95% CI)) increased at 3 months (+14.8 (10.6 to 18.9) and +11.2 (6.4 to 16) letters in the LOADING and PRN group, respectively) and remained significantly higher than baseline over the entire follow-up in both groups (all p<0.001). At 24 months, there was no difference in VA between the LOADING and PRN group (87.8 (13.8) vs 90.3 (11.3) letters, p=0.36) but the LOADING group received significantly more injections (median (Q1-Q3)) than the PRN (4.5 (3-7) vs 2.5 (2-3.2), p<0.0001). The iCNV recurrences were similar in both groups. Conclusions: iCNV responded well to anti-VEGF with significant and sustained VA improvement. The loading phase did not confer any advantage in terms of outcomes. PRN regimen from the beginning was as effective as more intensive treatment