Background/aimsTo evaluate the efficacy and safety of the PreserFlo MicroShunt glaucoma device in a multicentre cohort study.MethodsAll consecutive patients who received the microshunt with mitomycin-C (MMC) 0.4 mg/mL from May 2019 to September 2020 in three UK tertiary centres. Primary outcome at 1 year was a complete success, with failure defined as intraocular pressure (IOP) >21 mmHg or <20% reduction, IOP≤5 mmHg with any decreased vision on two consecutive visits, reoperation or loss of light perception vision. Secondary outcomes were IOP, best-corrected visual acuity, medications, complications, interventions and reoperations. We also performed subgroup analyses for severe glaucoma and assessed risk factors for failure.Results104 eyes had 1-year follow-up. Complete and qualified success at 1 year were achieved in 51.9% (N=54) and 16.4% (N=17), respectively, and failure occurred in 31.7% (N=33). There was a significant reduction in IOP (mmHg) from preoperatively (23.4±0.8, N=104) to 12 months (14.7±0.6, N=104) (p<0.0001). Antiglaucoma medications also decreased from preoperatively (3.4±0.1, N=104) to 12 months (0.7±0.1, N=104) (p<0.0001). Multivariate analyses showed an association between higher mean deviation and failure (HR 1.055, 95% CI 1.0075 to 1.11, p=0.0227). Complications were hypotony (19.2%; N=20), choroidal detachments (10.6%; N=11), hyphaema (5.8%; N=6) and bleb leak (5.8%; N=6). Needling and 5-fluorouracil injections were performed in 12.5% (N=13) and 33.7% (N=35), respectively, and 11.5% (N=12) required revision surgery.ConclusionThe PreserFlo MicroShunt with MMC 0.4 mg/mL showed an overall success rate of 68.3% at 1 year, and led to significant IOP and medication reduction with a low rate of adverse effects.

BackgroundLarge databases permit quantitative description of genes in terms of intolerance to loss of function (‘haploinsufficiency’) and prevalence of missense variants. We explored these parameters in inherited retinal disease (IRD) genes.MethodsIRD genes (from the ‘RetNet’ resource) were classified by probability of loss of function intolerance (pLI) using online Genome Aggregation Database (gnomAD) and DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) databases. Genes were identified having pLI ≥0.9 together with one or both of the following: upper bound of CI <0.35 for observed to expected (o/e) ratio of loss of function variants in the gnomAD resource; haploinsufficiency score <10 in the DECIPHER resource. IRD genes in which missense variants appeared under-represented or over-represented (Z score for o/e ratio of <−2.99 or >2.99, respectively) were also identified. The genes were evaluated in the gene ontology Protein Analysis THrough Evolutionary Relationships (PANTHER) resource.ResultsOf 280 analysed genes, 39 (13.9%) were predicted loss of function intolerant. A greater proportion of X-linked than autosomal IRD genes fulfilled these criteria, as expected. Most autosomal genes were associated with dominant disease. PANTHER analysis showed >100 fold enrichment of spliceosome tri-snRNP complex assembly. Most encoded proteins were longer than the median length in the UniProt database. Fourteen genes (11 of which were in the ‘haploinsufficient’ group) showed under-representation of missense variants. Six genes (SAMD11, ALMS1, WFS1, RP1L1, KCNV2, ADAMTS18) showed over-representation of missense variants.ConclusionA minority of IRD-associated genes appear to be ‘haploinsufficient’. Over-representation of spliceosome pathways was observed. When interpreting genetic tests, variants found in genes with over-representation of missense variants should be interpreted with caution.

Aravind Eye Care System approved the study. All research adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent.No animal subjects were used in this study.