An assessment of prevalence of Type 1 CFI rare variants in European AMD, and why lack of broader genetic data hinders development of new treatments and healthcare access

PurposeAdvanced age-related macular degeneration (AAMD) risk is associated with rare complement Factor I (FI) genetic variants associated with low FI protein levels (termed ‘Type 1’), but it is unclear how variant prevalences differ between AMD patients from different ethnicities.MethodsCollective prevalence of Type 1 CFI rare variant genotypes were examined in four European AAMD datasets. Collective minor allele frequencies (MAFs) were sourced from the natural history study SCOPE, the UK Biobank, the International AMD Genomics Consortium (IAMDGC), and the Finnish Biobank Cooperative (FINBB), and compared to paired control MAFs or background population prevalence rates from the Genome Aggregation Database (gnomAD). Due to a lack of available genetic data in non-European AAMD, power calculations were undertaken to estimate the AAMD population sizes required to identify statistically significant association between Type 1 CFI rare variants and disease risk in different ethnicities, using gnomAD populations as controls.ResultsType 1 CFI rare variants were enriched in all European AAMD cohorts, with odds ratios (ORs) ranging between 3.1 and 7.8, and a greater enrichment was observed in dry AMD from FINBB (OR 8.9, 95% CI 1.49–53.31). The lack of available non-European AAMD datasets prevented us exploring this relationship more globally, however a statistical association may be detectable by future sequencing studies that sample approximately 2,000 AAMD individuals from Ashkenazi Jewish and Latino/Admixed American ethnicities.ConclusionsThe relationship between Type 1 CFI rare variants increasing odds of AAMD are well established in Europeans, however the lack of broader genetic data in AAMD has adverse implications for clinical development and future commercialisation strategies of targeted FI therapies in AAMD. These findings emphasise the importance of generating more diverse genetic data in AAMD to improve equity of access to new treatments and address the bias in health care.</p

Changes in the geometry of modern daily disposable soft contact lenses during wear

Abstract The geometry of contact lenses can be altered by wear but determining the changes that occur in soft contact lenses (SCLs) is challenging. This study aimed to investigate the shape alterations of daily disposable SCLs after wear using swept-source optical coherence tomography (SS-OCT). Forty-five eyes with myopia of − 3.00 diopters (D) were enrolled. The participants wore three types of SCLs: hydrogel lens (nesofilcon A) and silicone hydrogel lenses (delefilcon A and stenfilcon A). The SCLs were scanned 3–6 min after lens removal. We found a significant decrease in the SCL anterior curvature: 0.24 ± 0.17 mm for nesofilcon A, 0.44 ± 0.21 mm for delefilcon A, and 0.53 ± 0.29 mm for stenfilcon A. The changes in the anterior curvature of SCLs correlated moderately with the mean corneal keratometry; Pearson’s correlation coefficients for nesofilcon A and delefilcon A were 0.57 and 0.52, respectively (P < 0.001). A statistically significant change in the total diameter was observed in SCL made of stenfilcon A (0.39 mm, P < 0.001). To conclude, the central radii of curvature decreased after a wearing period for all three types of daily disposable SCLs to imitate the anterior corneal surface, however, the changes in other geometrical parameters measured with SS-OCT were lens-specific

Ophthalmic complications of endoscopic sinus surgery

Abstract Introduction: The proximity of the paranasal sinuses to the orbit and its contents allows the occurence of injuries in both primary or revision surgery. The majority of orbital complications are minor. The major complications are seen in 0.01-2.25% and some of them can be serious, leading to permanent dysfunction. Objective: The aim of this study was to determine the risk and type of ophthalmic complications among patients operated due to a chronic rhinosinusitis. Methods: This is a retrospective study of 1658 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis with or without polyps or mucocele. Surgeries were performed under general anesthesia in all cases and consisted of polyps' removal, followed by middle metal antrostomy, partial or complete ethmoidectomy, frontal recess surgery and sphenoid surgery if necessary. The ophthalmic complications were classified according to type, frequency and clinical findings. Results: In our material 32.68% of the patients required revision surgery and only 10.1% had been previously operated in our Department. Overall complications occurred in 11 patients (0.66%). Minor complications were observed in 5 patients (0.3%) with the most frequent being periorbital ecchymosis with or without emphysema. Major complications were observed in one patient (0.06%) and were related to a lacrimal duct injury. Severe complications occurred in 5 cases (0.3%), with 2 cases and referred to a retroorbital hematoma, optic nerve injury (2 cases) and one case of extraocular muscle injury. Conclusions: Orbital complications of endoscopic nasal surgery are rare. The incidence of serious complications, causing permanent disabilities is less than 0.3%. The most important parameters responsible for complications are extension of the disease, previous endoscopic surgery and coexisting anticoagulant treatment

Change in the geometry of positive- and negative-powered soft contact lenses during wear.

Contact lens wear causes mutual interactions between the ocular surface and the lens, which may affect comfort as well as vision. The aim of this study was to examine deformations in modern positive- and negative-powered silicone hydrogel soft contact lenses (SiH SCLs) after 7 days of continuous wear. This pre-post interventional study included 64 eyes: 42 eyes with myopia of -3.00 D and 22 eyes with hyperopia of +3.00 D. All patients underwent general ophthalmic examination, corneal topography/tomography, total corneal and epithelial thickness mapping, and specular microscopy before and after the wearing period. SiH SCLs made of senofilcon A were worn continuously for 7 days on all eligible eyes. The geometry of the new and used lenses was measured 3 to 6 minutes after removal in two perpendicular planes using a custom-made swept source optical coherence tomography (SS-OCT) system for in vitro measurements. The anterior and posterior radii of curvature decreased in -3.00 D lenses in two perpendicular planes. This effect correlated significantly with average keratometry of the cornea. Sagittal lens height was lower in +3.00 D lens after wear, which correlated moderately with the corneal sagittal height. A significant decrease in central corneal epithelial thickness was observed after wearing +3.0 D lenses. In conclusion, SiH SCLs made of senofilcon A undergo minor deformations after 7-day continuous wear. Geometry modifications are different for -3.00 D and +3.00 D lenses, and they imitate the shape of the anterior eye surface. These geometric changes are accompanied by a decrease in the central thickness of corneal epithelium after +3.00 D lens wear