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.

Purpose: To compare the survival rate 1 year after Descemet membrane endothelial keratoplasty (DMEK) in pseudophakic eyes versus combined phacoemulsification and DMEK (triple-DMEK). Methods: Retrospective, interventional, consecutive case series. From all DMEKs performed from January 1, 2017, to June 30, 2018, we selected those performed in pseudophakic eyes (pseudophakic DMEK) and those that underwent triple-DMEK. We compared the survival rate 1 year after surgery between both groups and between the Fuchs endothelial dystrophy (FED) cases in both groups, plus the FED cases versus the pseudophakic bullous keratopathy (PBK) cases in the pseudophakic DMEK group. Second, we compared rebubbling rates and the influence of the use of gas or corneal sutures on rebubbling and dislocation rates. Results: A total of 329 eyes were included (218 eyes pseudophakic DMEK and 111 eyes triple-DMEK). The survival rate at 1 year was 79.8% and 90%, respectively (P = 0.03). When only FED cases were included (133 pseudophakic DMEK and 108 triple-DMEK), no significant difference was found (87.9% vs. 90.7%, P = 0.59). Within the pseudophakic DMEK group, the survival rate was higher in FED cases (87.8%) compared with PBK cases (66.6%) (P = 0.0001). Rebubbling rates were 21.1% (pseudophakic DMEK) and 17.1% (triple-DMEK) (P = 0.39). The use of gas versus air or placing corneal sutures did not seem to influence the rebubbling (P = 0.64 and P = 0.13, respectively) or dislocation rates (P = 0.71 and P = 0.53, respectively). Conclusions: In the FED cases, performing phacoemulsification before DMEK or doing a combined procedure did not seem to affect the rebubbling or survival rate up to 1 year postoperatively. PBK was associated with a higher failure rate compared with that of FED.

The master regulator of the fibrosis cascade is the myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway, making it a key target for anti-fibrotic therapeutics. In the past, inhibitors and small interfering RNAs (siRNAs) targeting the MRTF-B gene have been deployed to counter fibrosis in the eye, with the latter showing promising results. However, the biggest challenge in implementing siRNA therapeutics is the method of delivery. In this study, we utilised the novel, pH-sensitive, cationic lipid CL4H6, which has previously demonstrated potent targeting of hepatocytes and endosomal escape, to safely and efficiently deliver an MRTF-B siRNA into human conjunctival fibroblasts. We prepared two lipid nanoparticle (LNP) formulations, incorporating targeting cleavable peptide cY in one of them, and measured their physicochemical properties and silencing effect in human conjunctival fibroblasts. Both proved to be non-cytotoxic at a concentration of 50 nM and effectively silenced the MRTF-B gene in vitro, with the targeting cleavable peptide not affecting the silencing efficiency [LNP with cY: 62.1% and 81.5% versus LNP without cY: 77.7% and 80.2%, at siRNA concentrations of 50 nM (p = 0.06) and 100 nM (p = 0.09), respectively]. On the other hand, the addition of the targeting cleavable peptide significantly increased the encapsulation efficiency of the LNPs from 92.5% to 99.3% (p = 0.0005). In a 3D fibroblast-populated collagen matrix model, both LNP formulations significantly decreased fibroblast contraction after a single transfection. We conclude that the novel PEGylated CL4H6-MRTF-B siRNA-loaded LNPs represent a promising therapeutic approach to prevent conjunctival fibrosis after glaucoma filtration surgery.