Alcohol, Intraocular Pressure, and Open-Angle Glaucoma: A Systematic Review and Meta-analysis.

TOPIC: This systematic review and meta-analysis summarizes the existing evidence for the association of alcohol use with intraocular pressure (IOP) and open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding and quantifying these associations may aid clinical guidelines or treatment strategies and shed light on disease pathogenesis. The role of alcohol, a modifiable factor, in determining IOP and OAG risk also may be of interest from an individual or public health perspective. METHODS: The study protocol was preregistered in the Open Science Framework Registries (https://osf.io/z7yeg). Eligible articles (as of May 14, 2021) from 3 databases (PubMed, Embase, Scopus) were independently screened and quality assessed by 2 reviewers. All case-control, cross-sectional, and cohort studies reporting a quantitative effect estimate and 95% confidence interval (CI) for the association between alcohol use and either IOP or OAG were included. The evidence for the associations with both IOP and OAG was qualitatively summarized. Effect estimates for the association with OAG were pooled using random effects meta-analysis. Studies not meeting formal inclusion criteria for systematic review, but with pertinent results, were also appraised and discussed. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: Thirty-four studies were included in the systematic review. Evidence from 10 studies reporting an association with IOP suggests that habitual alcohol use is associated with higher IOP and prevalence of ocular hypertension (IOP > 21 mmHg), although absolute effect sizes were small. Eleven of 26 studies, comprising 173 058 participants, that tested for an association with OAG met inclusion criteria for meta-analysis. Pooled effect estimates indicated a positive association between any use of alcohol and OAG (1.18; 95% confidence interval [CI], 1.02-1.36; P = 0.03; I2 = 40.5%), with similar estimates for both prevalent and incident OAG. The overall GRADE certainty of evidence was very low. CONCLUSIONS: Although this meta-analysis suggests a harmful association between alcohol use and OAG, our results should be interpreted cautiously given the weakness and heterogeneity of the underlying evidence base, the small absolute effect size, and the borderline statistical significance. Nonetheless, these findings may be clinically relevant, and future research should focus on improving the quality of evidence.

From compliment to insult: genetics of the complement system in physiology and disease in the human retina.

Age-related macular degeneration (AMD) is a major cause of visual impairment that affects the central retina. Genome wide association studies and candidate gene screens have identified members of the complement pathway as contributing to the risk of AMD. In this review, we discuss the complement system, its importance in retinal development and normal physiology, how its dysregulation may contribute to disease, and how it might be targeted to prevent damage to the aging choriocapillaris in AMD.

Smoking, Corneal Biomechanics, and Glaucoma: Results From Two Large Population-Based Cohorts.

Purpose: Smoking may influence measured IOP through an effect on corneal biomechanics, but it is unclear whether this factor translates into an increased risk for glaucoma. This study aimed to examine the association of cigarette smoking with corneal biomechanical properties and glaucoma-related traits, and to probe potential causal effects using Mendelian randomization (MR). Methods: Cross-sectional analyses within the UK Biobank (UKB) and Canadian Longitudinal Study on Aging (CLSA) cohorts. Multivariable linear and logistic regression models were used to assess associations of smoking (status, intensity, and duration) with corneal hysteresis (CH), corneal resistance factor, IOP, inner retinal thicknesses, and glaucoma. Two-sample MR analyses were performed. Results: Overall, 68,738 UKB (mean age, 56.7 years; 54.7% women) and 22 845 CLSA (mean age, 62.7 years; 49.1% women) participants were included. Compared with nonsmokers, smokers had a higher CH (UKB, +0.48 mm Hg; CLSA, +0.57 mm Hg; P < 0.001) and corneal resistance factor (UKB, +0.47 mm Hg; CLSA, +0.60 mm Hg; P < 0.001) with evidence of a dose-response effect in both studies. Differential associations with Goldmann-correlated IOP (UKB, +0.25 mm Hg; CLSA, +0.36 mm Hg; P < 0.001) and corneal-compensated IOP (UKB, -0.28 mm Hg; CLSA, -0.32 mm Hg; P ≤ 0.001) were observed. Smoking was not associated with inner retinal thicknesses or glaucoma status in either study. MR provided evidence for a causal effect of smoking on corneal biomechanics, especially higher CH. Conclusions: Cigarette smoking seems to increase corneal biomechanical resistance to deformation, but there was little evidence to support a relationship with glaucoma. This outcome may result in an artefactual association with measured IOP and could account for discordant results with glaucoma in previous epidemiological studies.

The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population.

PURPOSE: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. PARTICIPANTS: Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. METHODS: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. MAIN OUTCOME MEASURES: Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. RESULTS: In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P < 0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P < 0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P < 0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17-1.45; P < 0.001). Stronger associations with glaucoma (P interaction = 0.001) were noted in participants with a higher glaucoma polygenic risk score. CONCLUSIONS: Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ethnicity is not biology: retinal pigment score to evaluate biological variability from ophthalmic imaging using machine learning.

Background: Few metrics exist to describe phenotypic diversity within ophthalmic imaging datasets, with researchers often using ethnicity as an inappropriate marker for biological variability. Methods: We derived a continuous, measured metric, the retinal pigment score (RPS), that quantifies the degree of pigmentation from a colour fundus photograph of the eye. RPS was validated using two large epidemiological studies with demographic and genetic data (UK Biobank and EPIC-Norfolk Study). Findings: A genome-wide association study (GWAS) of RPS from UK Biobank identified 20 loci with known associations with skin, iris and hair pigmentation, of which 8 were replicated in the EPIC-Norfolk cohort. There was a strong association between RPS and ethnicity, however, there was substantial overlap between each ethnicity and the respective distributions of RPS scores. Interpretation: RPS serves to decouple traditional demographic variables, such as ethnicity, from clinical imaging characteristics. RPS may serve as a useful metric to quantify the diversity of the training, validation, and testing datasets used in the development of AI algorithms to ensure adequate inclusion and explainability of the model performance, critical in evaluating all currently deployed AI models. The code to derive RPS is publicly available at: https://github.com/uw-biomedical-ml/retinal-pigmentation-score. Funding: The authors did not receive support from any organisation for the submitted work.

UK Biobank retinal imaging grading: methodology, baseline characteristics and findings for common ocular diseases.

BACKGROUND/OBJECTIVES: This study aims to describe the grading methods and baseline characteristics for UK Biobank (UKBB) participants who underwent retinal imaging in 2009-2010, and to characterise individuals with retinal features suggestive of age-related macular degeneration (AMD), glaucoma and retinopathy. METHODS: Non-mydriatic colour fundus photographs and macular optical coherence tomography (OCT) scans were manually graded by Central Administrative Research Facility certified graders and quality assured by clinicians of the Network of Ophthalmic Reading Centres UK. Captured retinal features included those associated with AMD (≥1 drusen, pigmentary changes, geographic atrophy or exudative AMD; either imaging modality), glaucoma (≥0.7 cup-disc ratio, ≥0.2 cup-disc ratio difference between eyes, other abnormal disc features; photographs only) and retinopathy (characteristic features of diabetic retinopathy with or without microaneurysms; either imaging modality). Suspected cases of these conditions were characterised with reference to diagnostic records, physical and biochemical measurements. RESULTS: Among 68,514 UKBB participants who underwent retinal imaging, the mean age was 57.3 years (standard deviation 8.2), 45.7% were men and 90.6% were of White ethnicity. A total of 64,367 participants had gradable colour fundus photographs and 68,281 had gradable OCT scans in at least one eye. Retinal features suggestive of AMD and glaucoma were identified in 15,176 and 2184 participants, of whom 125 (0.8%) and 188 (8.6%), respectively, had a recorded diagnosis. Of 264 participants identified to have retinopathy with microaneurysms, 251 (95.1%) had either diabetes or hypertension. CONCLUSIONS: This dataset represents a valuable addition to what is currently available in UKBB, providing important insights to both ocular and systemic health.

Two-year recall for people with no diabetic retinopathy: a multi-ethnic population-based retrospective cohort study using real-world data to quantify the effect.

BACKGROUND/AIMS: The English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual screening. Less frequent screening has been advocated among PLD without diabetic retinopathy (DR), but evidence for each ethnic group is limited. We examined the potential effect of biennial versus annual screening on the detection of sight-threatening diabetic retinopathy (STDR) and proliferative diabetic retinopathy (PDR) among PLD without DR from a large urban multi-ethnic English DESP. METHODS: PLD in North-East London DESP (January 2012 to December 2021) with no DR on two prior consecutive screening visits with up to 8 years of follow-up were examined. Annual STDR and PDR incidence rates, overall and by ethnicity, were quantified. Delays in identification of STDR and PDR events had 2-year screening intervals been used were determined. FINDINGS: Among 82 782 PLD (37% white, 36% South Asian, and 16% black people), there were 1788 incident STDR cases over mean (SD) 4.3 (2.4) years (STDR rate 0.51, 95% CI 0.47 to 0.55 per 100-person-years). STDR incidence rates per 100-person-years by ethnicity were 0.55 (95% CI 0.48 to 0.62) for South Asian, 0.34 (95% CI 0.29 to 0.40) for white, and 0.77 (95% CI 0.65 to 0.90) for black people. Biennial screening would have delayed diagnosis by 1 year for 56.3% (1007/1788) with STDR and 43.6% (45/103) with PDR. Standardised cumulative rates of delayed STDR per 100 000 persons for each ethnic group were 1904 (95% CI 1683 to 2154) for black people, 1276 (95% CI 1153 to 1412) for South Asian people, and 844 (95% CI 745 to 955) for white people. INTERPRETATION: Biennial screening would have delayed detection of some STDR and PDR by 1 year, especially among those of black ethnic origin, leading to healthcare inequalities.

The Association of Alcohol Consumption with Glaucoma and Related Traits: Findings from the UK Biobank.

PURPOSE: To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. PARTICIPANTS: UK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407). METHODS: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. MAIN OUTCOME MEASURES: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. RESULTS: Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P < 0.001) and thinner mGCIPL (-0.17 µm; P = 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P = 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P < 0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol-IOP associations were observed in participants at higher genetic susceptibility to glaucoma (Pinteraction < 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness. CONCLUSIONS: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Ethnic disparities in progression rates for sight-threatening diabetic retinopathy in diabetic eye screening: a population-based retrospective cohort study.

INTRODUCTION: The English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual eye screening. We examined incidence and determinants of sight-threatening diabetic retinopathy (STDR) in a sociodemographically diverse multi-ethnic population. RESEARCH DESIGN AND METHODS: North East London DESP cohort data (January 2012 to December 2021) with 137 591 PLD with no retinopathy, or non-STDR at baseline in one/both eyes, were used to calculate STDR incidence rates by sociodemographic factors, diabetes type, and duration. HR from Cox models examined associations with STDR. RESULTS: There were 16 388 incident STDR cases over a median of 5.4 years (IQR 2.8-8.2; STDR rate 2.214, 95% CI 2.214 to 2.215 per 100 person-years). People with no retinopathy at baseline had a lower risk of sight-threatening diabetic retinopathy (STDR) compared with those with non-STDR in one eye (HR 3.03, 95% CI 2.91 to 3.15, p<0.001) and both eyes (HR 7.88, 95% CI 7.59 to 8.18, p<0.001). Black and South Asian individuals had higher STDR hazards than white individuals (HR 1.57, 95% CI 1.50 to 1.64 and HR 1.36, 95% CI 1.31 to 1.42, respectively). Additionally, every 5-year increase in age at inclusion was associated with an 8% reduction in STDR hazards (p<0.001). CONCLUSIONS: Ethnic disparities exist in a health system limited by capacity rather than patient economic circumstances. Diabetic retinopathy at first screen is a strong determinant of STDR development. By using basic demographic characteristics, screening programmes or clinical practices can stratify risk for sight-threatening diabetic retinopathy development.

Quantification and Predictors of OCT-Based Macular Curvature and Dome-Shaped Configuration: Results From the UK Biobank.

Purpose: To investigate macular curvature, including the evaluation of potential associations and the dome-shaped macular configuration, given the increasing myopia prevalence and expected associated macular malformations. Methods: The study included a total of 65,440 subjects with a mean age (± SD) of 57.3 ± 8.11 years with spectral-domain optical coherence tomography (OCT) data from a unique contemporary resource for the study of health and disease that recruited more than half a million people in the United Kingdom (UK Biobank). A deep learning model was used to segment the retinal pigment epithelium. The macular curvature of the OCT scans was calculated by polynomial fit and evaluated. Further, associations with demographic, functional, ocular, and infancy factors were examined. Results: The overall macular curvature values followed a Gaussian distribution with high inter-eye agreement. Although all of the investigated parameters, except maternal smoking, were associated with the curvature in a multilinear analysis, ethnicity and refractive error consistently revealed the most significant effect. The prevalence of a macular dome-shaped configuration was 4.8% overall, most commonly in Chinese subjects as well as hypermetropic eyes. An increasing frequency up to 22.0% was found toward high refractive error. Subretinal fluid was rarely found in these eyes. Conclusions: Macular curvature revealed associations with demographic, functional, ocular, and infancy factors, as well as increasing prevalence of a dome-shaped macular configuration in high refractive error including high myopia and hypermetropia. These findings imply different pathophysiologic processes that lead to macular development and might open new fields to future myopia and macula research.

The Association of Female Reproductive Factors with Glaucoma and Related Traits: A Systematic Review.

TOPIC: This systematic review summarizes evidence for associations between female reproductive factors (age at menarche, parity, oral contraceptive [OC] use, age at menopause, and postmenopausal hormone [PMH] use) and intraocular pressure (IOP) or open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding the associations between female reproductive factors and glaucoma may shed light on the disease pathogenesis and aid clinical prediction and personalized treatment strategies. Importantly, some factors are modifiable, which may lead to new therapies. METHODS: Two reviewers independently extracted articles in MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases to identify relevant studies. Eligibility criteria included studies with human subjects aged > 18 years; a measured outcome of either IOP or OAG; a cohort, case-control, cross-sectional, or randomized controlled trial design; a reported measure of association, such as the hazard ratio, relative risk, odds ratio, or mean difference, with an associated confidence interval; and a measured exposure of at least 1 of the following variables: age at menarche, parity, OC use, age at menopause, or PMH use. RESULTS: We included a total of 27 studies. Substantial differences in study designs, exposure and treatment levels, treatment durations, and variable reporting precluded a meaningful quantitative synthesis of the identified studies. Overall, relatively consistent associations between PMH use and a lower IOP were identified. Estrogen-only PMH use may be associated with lower OAG risk, which may be modified by race. No significant associations were found with combined estrogen-and-progesterone PMH use. No strong associations between parity or age at menarche and glaucoma were found, but a younger age at menopause was associated with an increased glaucoma risk, and adverse associations were identified with a longer duration of OC use, though no overall association with OC use was found. CONCLUSIONS: The association between PMH use and lower IOP or OAG risk is a potentially clinically relevant and modifiable risk factor and should be investigated further, although this needs to be interpreted in the context of a high risk of bias across included studies. Future research should examine associations with IOP specifically and how the relationship between genetic factors and OAG risks may be influenced by female reproductive factors.

Contextualizing single-arm trials with real-world data: An emulated target trial comparing therapies for neovascular age-related macular degeneration.

One-in-four ophthalmology trials are single-armed, which poses challenges to their interpretation. We demonstrate how real-world cohorts used as external/synthetic control arms can contextualize such trials. We herein emulated a target trial on the intention-to-treat efficacy of off-label bevacizumab (q6w) pro re nata relative to fixed-interval aflibercept (q8w) for improving week 54 visual acuity of eyes affected by neovascular age-related macular degeneration. The bevacizumab arm (n = 65) was taken from the ABC randomized controlled trial. A total of 4,471 aflibercept-treated eyes aligning with the ABC trial eligibility were identified from electronic health records and synthetic control arms were created by emulating randomization conditional on age, sex, and baseline visual read via exact matching and propensity score methods. We undertook an inferiority analysis on mean difference at 54 weeks; outcomes regression on achieving a change in visual acuity of greater than or equal to 15, greater than or equal to 10, and less than or equal to -15 Early Treatment Diabetic Retinopathy (ETDRS) letters at week 54; and a time-to-event analysis on achieving a change in visual acuity of greater than or equal to 15, greater than or equal to 10, and less than or equal to -15 ETDRS letters by week 54. The findings suggest off-label bevacizumab to be neither inferior nor superior to licensed aflibercept. Our study highlights how real-world cohorts representing the counterfactual intervention could aid the interpretation of single-armed trials when analyzed in accord to the target trial framework. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? One-in-four randomized controlled trials in ophthalmology are single-armed, which poses challenges for interpreting their efficacy relative to standard of care. Recent conceptual advances in the methods of causal inference and in the emulation of target trials suggests that the standard-of-care arms representing the counterfactual intervention can be approximated with observational data. WHAT QUESTION DID THIS STUDY ADDRESS? How real-world cohorts representing the counterfactual intervention can aid the interpretation of single-armed ophthalmological trials. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Our study highlights how real-world cohorts representing the counterfactual intervention could aid the interpretation of single-armed ophthalmological trials when undertaken in accord with the target trial framework. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? External counterfactual arms could reduce the time and cost to reach potential regulatory approval.

Quantification of Key Retinal Features in Early and Late Age-Related Macular Degeneration Using Deep Learning.

PURPOSE: We sought to develop and validate a deep learning model for segmentation of 13 features associated with neovascular and atrophic age-related macular degeneration (AMD). DESIGN: Development and validation of a deep-learning model for feature segmentation. METHODS: Data for model development were obtained from 307 optical coherence tomography volumes. Eight experienced graders manually delineated all abnormalities in 2712 B-scans. A deep neural network was trained with these data to perform voxel-level segmentation of the 13 most common abnormalities (features). For evaluation, 112 B-scans from 112 patients with a diagnosis of neovascular AMD were annotated by 4 independent observers. The main outcome measures were Dice score, intraclass correlation coefficient, and free-response receiver operating characteristic curve. RESULTS: On 11 of 13 features, the model obtained a mean Dice score of 0.63 ± 0.15, compared with 0.61 ± 0.17 for the observers. The mean intraclass correlation coefficient for the model was 0.66 ± 0.22, compared with 0.62 ± 0.21 for the observers. Two features were not evaluated quantitatively because of a lack of data. Free-response receiver operating characteristic analysis demonstrated that the model scored similar or higher sensitivity per false positives compared with the observers. CONCLUSIONS: The quality of the automatic segmentation matches that of experienced graders for most features, exceeding human performance for some features. The quantified parameters provided by the model can be used in the current clinical routine and open possibilities for further research into treatment response outside clinical trials.

Retinitis pigmentosa and bilateral cystoid macular oedema in a patient heterozygous for the RIM1 mutation previously associated with cone-rod dystrophy 7.

BACKGROUND: Autosomal dominant cone-rod dystrophy 7 (CORD7) has been previously associated with the RIM1 c.2459G>A (Arg820His) mutation. Cystoid macular oedema (CMO) is a rare feature of CORD and has not been described in CORD7. We report a patient who was heterozygous for the RIM1 mutation with bilateral CMO and who manifested a retinitis pigmentosa phenotype. MATERIALS AND METHODS: The patient's medical notes were retrospectively reviewed over an 18-month period. Genetic testing was performed by next generation sequencing for a panel of 176 genes associated with retinal dystrophy. RESULTS: A 34-year-old man presented with a 5-year history of bilateral floaters and blurred vision. Visual acuity was 20/23 and 20/33 in the right and left eyes, respectively. Optical coherence tomography scans revealed bilateral CMO. Goldmann visual field tests detected mid-peripheral ring scotomas. Electrodiagnostic testing was overall consistent with a primary photoreceptor abnormality involving both rods and cones. Subsequent genetic testing identified heterozygosity for the RIM1 c.2459G>A (Arg820His) mutation. Various treatments for CMO were trialled unsuccessfully. However, at his latest clinic appointment the CMO had partially improved following topical brinzolamide therapy. Most recent visual acuity was 20/25 in the right eye and 20/24 in the left eye. CONCLUSIONS: This is the first reported case of bilateral CMO in association with the RIM1 mutation. Overall, our findings were more consistent with a phenotype of retinitis pigmentosa. This could imply that the RIM1 mutation causes diverse retinal dystrophies, or that the previously described CORD7 phenotype resulted from a different variant on the same haplotype.

Fixed bimonthly aflibercept in naïve and switched neovascular age-related macular degeneration patients: one year outcomes.

AIM: To determine real life clinical outcomes in poorly responsive and treatment-naïve neovascular age related macular degeneration (nvAMD) patients using bimonthly fixed dosing aflibercept regimen. METHODS: This was a retrospective study of 165 eyes with nvAMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata (PRN) ranibizumab/bevacizumab due to poor response (107 eyes), or treatment-naïve (58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline were assessed using the Wilcoxon signed-rank test. The proportion of patients maintaining BCVA (<15 letters loss) at 12mo was also evaluated. RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and naïve aflibercept groups respectively (P<0.01). BCVA was maintained in 95.3% of switched and 96.6% of naïve patients. CRT at month 12 showed a decrease of -6.16 µm in the switched group and -35.36 µm in the naïve group (P<0.01). Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections (naïve group), 7.5 injections (switched group) and 4 clinic visits per year. CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-naïve and poorly responsive nvAMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.