Lisch Epithelial Corneal Dystrophy Is Caused by Heterozygous Loss-of-Function Variants in MCOLN1.

PURPOSE: To report the genetic etiology of Lisch epithelial corneal dystrophy (LECD). DESIGN: Multicenter cohort study. METHODS: A discovery cohort of 27 individuals with LECD from 17 families, including 7 affected members from the original LECD family, 6 patients from 2 new families and 14 simplex cases, was recruited. A cohort of 6 individuals carrying a pathogenic MCOLN1 (mucolipin 1) variant was reviewed for signs of LECD. Next-generation sequencing or targeted Sanger sequencing were used in all patients to identify pathogenic or likely pathogenic variants and penetrance of variants. RESULTS: Nine rare heterozygous MCOLN1 variants were identified in 23 of 27 affected individuals from 13 families. The truncating nature of 7 variants and functional testing of 1 missense variant indicated that they result in MCOLN1 haploinsufficiency. Importantly, in the homozygous and compound-heterozygous state, 4 of 9 LECD-associated variants cause the rare lysosomal storage disorder mucolipidosis IV (MLIV). Autosomal recessive MLIV is a systemic disease and comprises neurodegeneration as well as corneal opacity of infantile-onset with epithelial autofluorescent lysosomal inclusions. However, the 6 parents of 3 patients with MLIV confirmed to carry pathogenic MCOLN1 variants did not have the LECD phenotype, suggesting MCOLN1 haploinsufficiency may be associated with reduced penetrance and variable expressivity. CONCLUSIONS: MCOLN1 haploinsufficiency is the major cause of LECD. Based on the overlapping clinical features of corneal epithelial cells with autofluorescent inclusions reported in both LECD and MLIV, it is concluded that some carriers of MCOLN1 haploinsufficiency-causing variants present with LECD.

Evaluating the forces involved in bubble management in DMEK surgery: mathematical and computational model with clinical implications.

PURPOSE: To model postoperative forces involved in Descemet membrane endothelial keratoplasty (DMEK) tissue adherence and bubble management, including the impact of surface tension on graft support, with a view towards clinical applications. SETTING: Tennent Institute of Ophthalmology, Glasgow, and James Watt School of Engineering, University of Glasgow, Glasgow, United Kingdom. DESIGN: Mathematical modelling and computer simulation. METHODS: Theoretical modelling of biphasic flow and interaction of gas, liquid and tissue within the anterior chamber for static horizontal scenario A (adherent DMEK with mobile bubble) and dynamic vertical scenario B (release of bubble due to pupil block following DMEK). RESULTS: The model assumed incompressibility for both fluids within realistically achievable pressure ranges. Cahn-Hilliard Navier-Stokes equations were discretised through the application of the Finite Element Method. Mathematical modelling and computer simulation showed bubble size, corneal curvature and force intensity influences surface tension support for DMEK tissue in scenario A. Scenario B demonstrated complex, uneven distribution of surface pressure on the DMEK graft during uncontrolled bubble release. Uneven pressure concentration can cause local tissue warping, with air/fluid displacement via capillary waves generated on the fluid-air interface adversely impacting DMEK support. CONCLUSIONS: We have quantitatively and qualitatively modelled the forces involved in DMEK adherence in normal circumstances. We have shown releasing air/gas can abruptly reduce DMEK tissue support via generation of large pressure gradients at the liquid/bubble/graft interfaces, creating negative local forces. Surgeons should consider these principles to reduce DMEK graft dislocation rates via optimised bubble size to graft size, longer acting bubble support and avoiding rapid decompression where possible.

Antimicrobials and antiseptics: Lowering effect on ocular surface bacterial flora - A systematic review.

Topical antimicrobials and antiseptics are used perioperatively to reduce the ocular surface bacteria flora (OSBF) that are involved in the development of post-operative infectious complications. However, their effectiveness is still a controversial topic. This systematic review, performed according to the PRISMA guidelines and registered in PROSPERO, aims to provide an overview of the efficacy of the agents currently used in peri-cataract surgery and -intravitreal injections (IVI) in lowering the OSBF. Although effective in lowering OSBF, perioperative topical antimicrobials are associated with the risk of resistance development, with no obvious additional benefit compared with topical antisepsis. Conversely, the effectiveness of topical antiseptics before cataract surgery and IVI is strongly supported. Based on the available evidence, perioperative antimicrobials are not recommended, whereas the perioperative use of antiseptics is strongly recommended as prophylactic treatment for lowering the infection due to OSBF. Post-operative antimicrobials may be considered in eyes at higher risk for infection.

Potential cost of assumptions within a visual assessment.

We report a man in his 80s who described sudden unilateral loss of vision, resulting in extensive urgent investigations by the accident and emergency department team. Subsequent evaluation of visual acuity with pinhole demonstrated significant improvement, triggering further questioning. It transpired that he was mistakenly wearing his wife's glasses, which accounted for his visual symptoms. This case illustrates the importance of a stepwise approach to visual assessment, and avoiding assumptions, as using the simple pinhole test could have avoided extensive investigations and their subsequent costs.

Clear corneal incision, an important step in modern cataract surgery: a review.

A clear corneal incision (CCI) is the most commonly used entrance site in modern phacoemulsification cataract surgery. Despite some initial concerns about increased endophthalmitis rates through a self-sealing CCI, recent literature suggests that the risk of infection with proper wound construction and all other necessary precautions is minimal. The technique of creating a clear corneal incision has, with recent developments in corneal imaging, undergone critical appraisal leading to a better understanding of incision architecture. Many surgeons operate through smaller incisions, and they have a wide choice of surgical instruments to create their corneal incisions. The aim of this review is to discuss the history and the current status of clear corneal incision creation, the design and materials of surgical blades, and the current trends in manufacturing and sustainability. Although disposable instruments have some advantages and are very popular, recycling, if possible, and avoiding unnecessary plastic waste are important considerations. In any case, the step of CCI is a small one for the surgeon, but a big one for the eye. That is why it has to be done with the utmost precision and in-depth knowledge is important.

Novel Map Biopsy Technique to Define the Extent of Infection Before Penetrating Keratoplasty for Acanthamoeba Keratitis.

PURPOSE: The purpose of this study was to report a novel approach of prepenetrating keratoplasty (PKP) corneal map biopsies to define the extent of Acanthamoeba cyst infiltration in recalcitrant Acanthamoeba keratitis. METHODS: Corneal map biopsies were performed 1 week before PKP. Four biopsies, 1 from each peripheral corneal quadrant, were obtained to delineate the extent of microscopic infection. Histological results of these map biopsies were used to determine the size and location of the subsequent PKP. RESULTS: In our first case, map biopsies revealed Acanthamoeba cysts in 2 of the 4 biopsies. This led to an inferotemporally eccentric 8.5-mm PKP. The final histology report indicated that the closest resection margin was 0.08 mm. In our second case, the peripheral map biopsies were clear and an inferiorly eccentric 8.25-mm PKP was performed. The final histology report indicated that the closest resection margin was 2.3 mm. Both grafts have remained clear at 6 months postoperatively. CONCLUSIONS: Map biopsies of the cornea can achieve total removal of the corneal tissues infested with Acanthamoeba cysts and prevent reinfection of the donor graft.

Estimations of Critical Clear Corneal Incisions Required for Lens Insertion in Cataract Surgery: A Mathematical Aspect.

In a routine cataract operation cornea tissue may be damaged when an intra-ocular lens (IOL) injector of diameter between 1.467 and 2.011 mm is inserted through an empirically designed 2.2 mm corneal incision. We aimed to model and estimate the minimal length of the incision required to avoid wound tear. It was assumed that the damage was caused by tissue fracture at the tips of the incision, and this fracture could be studied using damage and fracture mechanics. The criterion of the damage was caused by a tear governed by the critical energy release rate (ERR) G c , which is tissue dependent. Analytical and numerical studies were both conducted indicating the possibility of a safe and effective incision in cataract surgery. Six commonly used IOL injection systems were examined. Our results suggested that the recommended 2.2 mm incision cannot be treated as a universal threshold. Quicker IOL insertion may reduce wound damage. It was also recommended to advance IOL injector via its minor axis, and to cut the tear preferably along the circumferential direction due to tissue orthotropy. This study provides useful information and a deeper insight into the potential for mechanical damage to the corneal wound in cataract surgery.

Cost and time resourcing for ophthalmic simulation in the UK: a Royal College of Ophthalmologists' National Survey of regional Simulation Leads in 2021.

INTRODUCTION: Ophthalmic simulation is cost-effective in complication prevention. However, there is no consistent resource allocation to provide the necessary time and finance to sustain such activities. We wished to identify the current support for the regional Simulation Leads in the UK. METHODS: An online SurveyMonkey questionnaire was sent to all 26 UK ophthalmic regional Simulation Leads in February 2021 regarding current simulation activity and the degree of time and resource support available. RESULTS: There were 22 responses within 1 month (84.6% response rate). 72.7% run regular simulation induction events for new trainees. 60% run mandatory laser simulation events. 38.1% run immersive simulation (vitreous loss fire drill). 47.6% run yearly sub-specialty events. 45.5% were required to make additional work arrangements to run simulation events. 77.3% had no job plan time allocation for simulation. 59.1% dedicated >1 hr/week to simulation. 68.2% EYESI simulators were purchased via charity/endowments. 72.7% had access to dedicated dry lab simulation (40.9% wet lab). 40.9% used deanery funds to purchase initial model eyes (supplemented by charity (36.4%) and endowments (31.8%)). 65% used unspent study leave budgets for ongoing model eyes, yet 15% reported trainees purchasing their own. CONCLUSION: Nearly all ophthalmic simulation in the UK is undertaken via goodwill and personal commitment to excellence by the regional Simulation Leads. There is minimal allowance of time or finance for these vital activities, which is sporadic at best, and unsustainable. We call for the necessary investment and dedicated time allocation to permit ophthalmic simulation to be supported and maintained.