Real-World Experience in the Use of Immunosuppression for the Management of Inflammatory Eye Disease.

PURPOSE: Patients with sight-threatening inflammatory eye disease (IED) are maintained on systemic immunosuppression whilst in long-term clinical remission. There are no clear guidelines on the duration of remission before implementing treatment withdrawal. We present a real-world analysis on the use of immunosuppression in IED in long-term remission and consider strategies for withdrawal. METHODS: Adult IED patients on systemic immunosuppression were categorised into four disease groups: Corneal Transplant Survival Strategies (CTSS), Ocular Surface Disease (OSD), Non-infectious Uveitis (NIU) and Scleritis. Patients with Behçet's disease were excluded. Data on systemic immunosuppressants and biologics used; duration of treatment; reasons for drug discontinuation; disease activity/remission status; duration of clinical remission with an emphasis on patients who had been in remission for a minimum of 24 months were captured. RESULTS: Out of a total of 303 IED patients, 128 were on systemic immunosuppression with a clinical remission of their ocular disease for ≥24 months. The median duration of remission was 4-5 years with the longest duration of remission 22 years, and some patients on immunosuppression for up to 23 years. Sixty patients stopped at least one immunosuppressive agent without prior discussion with a health-care practitioner. CONCLUSION: Progressive conditions, such as cicatrising conjunctivitis may require lifelong immunosuppression, but patients with NIU and Scleritis and those on CTSS, immunosuppression withdrawal should be considered if they remain in remission for 2 years. Any patient stopping a medication should be contacted immediately for counselling. These data will better inform patients, encourage adherence and aide formal guideline development.

The impact of the first United Kingdom COVID-19 lockdown on environmental air pollution, digital display device use and ocular surface disease symptomatology amongst shielding patients.

Worldwide lockdown reduced air pollution during the first phase of the COVID-19 pandemic. The relationship between exposure to ambient air pollution, digital display device use and dry eye symptoms amongst patients with severe ocular surface disease (OSD) were considered. Symptoms and air pollutant concentrations for three different time periods (pre, during and post COVID-19 lockdown) were analysed in 35 OSD patients who achieved an immunosuppression risk-stratification score > 3 fulfilling the UK Government criteria for 12-week shielding. OSDI symptoms questionnaire, residential postcode air pollution data obtained from the Defra Automated Urban and Rural monitoring network for concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter (PM) with diameters below 10 µm and 2.5 µm, and English Indices of Deprivation were analysed. Significant reductions in NO2 and NOx concentrations were observed between pre- and during-lockdown periods, followed by a reversal in the post-lockdown period. Changes were linked to the Living Environment outdoor decile. A 12% increase (p = 0.381) in symptomatology during-lockdown was observed that reversed post-lockdown by 19% (p = 0.144). OSDI scores were significantly correlated with hours spent on digital devices (r2 = 0.243) but not with air pollutant concentrations. Lockdown measures reduced ambient air pollutants whilst OSD symptomatology persisted. Environmental factors such as increased time indoors and use of bluescreen digital devices may have partly played a role.

Gut Dysbiosis in Ocular Mucous Membrane Pemphigoid.

Mucous Membrane Pemphigoid is an orphan multi-system autoimmune scarring disease involving mucosal sites, including the ocular surface (OcMMP) and gut. Loss of tolerance to epithelial basement membrane proteins and generation of autoreactive T cell and/or autoantibodies are central to the disease process. The gut microbiome plays a critical role in the development of the immune system. Alteration in the gut microbiome (gut dysbiosis) affects the generation of autoreactive T cells and B cell autoantibody repertoire in several autoimmune conditions. This study examines the relationship between gut microbiome diversity and ocular inflammation in patients with OcMMP by comparing OcMMP gut microbiome profiles with healthy controls. DNA was extracted from faecal samples (49 OcMMP patients, 40 healthy controls), amplified for the V4 region of the 16S rRNA gene and sequenced using Illumina Miseq platform. Sequencing reads were processed using the bioinformatics pipeline available in the mothur v.1.44.1 software. After adjusting for participant factors in the multivariable model (age, gender, BMI, diet, proton pump inhibitor use), OcMMP cohort was found to be associated with lower number of operational taxonomic units (OTUs) and Shannon Diversity Index when compared to healthy controls. Within the OcMMP cohort, the number of OTUs were found to be significantly correlated with both the bulbar conjunctival inflammation score (p=0.03) and the current use of systemic immunotherapy (p=0.02). The linear discriminant analysis effect size scores indicated that Streptococcus and Lachnoclostridium were enriched in OcMMP patients whilst Oxalobacter, Clostridia uncultured genus-level group (UCG) 014, Christensenellaceae R-7 group and butyrate-producing bacteria such as Ruminococcus, Lachnospiraceae, Coprococcus, Roseburia, Oscillospiraceae UCG 003, 005, NK4A214 group were enriched in healthy controls (Log10 LDA score < 2, FDR-adjusted p <0.05). In conclusion, OcMMP patients have gut dysbiosis correlating with bulbar conjunctival inflammation and the use of systemic immunotherapies. This provides a framework for future longitudinal deep phenotyping studies on the role of the gut microbiome in the pathogenesis of OcMMP.