ROCK inhibitors in ophthalmology: A critical review of the existing clinical evidence.

Rho kinase (ROCK) inhibitors have emerged as a key therapeutic class of interest in ophthalmology over the last decade. Promising in vitro studies laid the foundations for the development of novel therapeutic agents that target the ROCK signalling pathway in ocular disease, with subsequent clinical trials supporting their use. Corneal endothelial disease, glaucoma, and vitreoretinal disease are the major pathologies in which ROCK inhibitors have been investigated to date. Ripasudil and netarsudil represent the current leaders in this pharmaceutical group, having been extensively validated and approved for use in glaucoma in some countries. Less substantial evidence exists for fasudil in ophthalmic use. ROCK inhibitors are also increasingly used in cultured endothelial cell grafting and as an adjunct to aid in endothelial cell migration and replication in Descemet's stripping procedures or Descemet's membrane injuries. This review has synthesised both established and emerging research to provide a practical guide to prescribing in this drug class. Drug efficacies, side effect profiles, and the demographic and clinical characteristics of appropriate drug candidates are discussed.

Prevalence of Keratoconus Based on Scheimpflug Imaging: The Raine Study.

PURPOSE: To describe the prevalence and systemic associations of keratoconus in young adults in Perth, Western Australia. DESIGN: Cross-sectional study. PARTICIPANTS: One thousand two hundred fifty-nine participants 20 years of age. METHODS: The Raine Study is a multigenerational, longitudinal cohort study based in Perth, Western Australia. This study represents a cross-sectional analysis of the birth cohort on returning for a 20-year follow-up. Participants underwent a detailed ophthalmic examination, including visual acuity assessment and Scheimpflug imaging using the Pentacam (Oculus, Wetzlar, Germany), and completed a health questionnaire. Keratoconus was defined as a Belin/Ambrόsio enhanced ectasia display score of 2.6 or more in either eye based on Pentacam imaging. MAIN OUTCOME MEASURES: Prevalence of keratoconus in this cohort. RESULTS: Of the 1259 participants, 50.8% were women and 85.7% were White. Fifteen participants had keratoconus in at least 1 eye, giving a prevalence of 1.2% (95% confidence interval, 0.7%-1.9%), or 1 in 84. A significant difference was found in best-corrected visual acuity (0.01 logarithm of the minimum angle of resolution vs. -0.05 logarithm of the minimum angle of resolution; P = 0.007), cylinder (1.25 diopters [D] vs. 0.25 D cylinder; P < 0.001) and spherical equivalent (-1.42 D vs. -0.50 D sphere; P = 0.02) on objective refraction, mean keratometry of the steep meridian (45.19 D vs. 43.76 D; P < 0.001), and mean corneal thickness at the thinnest point (475 µm vs. 536 µm; P < 0.001) between those with and without keratoconus. Keratoconus was associated with regular cigarette smoking (38.5% vs. 14.6%; P = 0.04), but showed no association with gender, race, body mass index, use of spectacles or contact lenses, history of allergic eye disease, or pregnancy. CONCLUSIONS: The prevalence of keratoconus in this Australian population-based study of 20-year-old adults was 1.2% (95% confidence interval, 0.7%-1.9%), or 1 in 84, which is one of the highest reported in the world. This has important implications for screening individuals at a younger age so that treatment can be initiated before disease progression.

Face Mask-Associated Recurrent Corneal Erosion Syndrome and Corneal Infection.

ABSTRACT: In the current coronavirus disease 2019 (COVID-19) pandemic, important public health measures such as the utilization of face masks has been widely enforced, including community-wide mandatory face mask use. During this period, there have been observations of an increasing number of patients presenting with dry eye symptoms among regular mask users with no history of ocular surface pathology. Individuals have reported being aware of air blowing upward from the mask into their eyes that is likely to increase the evaporation of their tear film leading to ocular irritation. Although face mask use is essential in combatting the COVID-19 pandemic, it is important to recognize the potential effects it may have on ocular health. We report a case of face mask-associated ocular complication. After an initial cornea abrasion from mask use, the patient developed recurrent corneal erosion syndrome that was complicated by microbial keratitis after the enforcement of mandatory mask use in public areas.

Optical coherence tomography analysis of patients with untreated diabetic macular edema.

PURPOSE: Diabetic macular edema (DME) is a major cause of vision loss. Diabetes patients with mild macular edema and good visual acuity are often observed carefully so that treatment can be instituted when central vision is threatened. Optimal frequency of monitoring of these patients is unknown. Our study aimed to gather more information to determine a safe interval for monitoring of patients with eyes that were not undergoing active treatment for DME and to correlate outcomes with clinical risk factors. METHODS: Study population: Ninety-seven eyes with optical coherence tomography (OCT) evidence of DME of 97 patients with diabetes. Study procedures: Retrospective review of medical records and macular OCT scans at a 6-12-month interval. Primary outcomes: Change in visual acuity and change in central subfield thickness (CSFT) between the initial and follow-up OCT scans. RESULTS: There was no significant change from median baseline visual acuity 6/9 (inter-quartile range 6/6-6/12) or from median baseline CSFT (290 µm, inter-quartile range 270-312 µm) over a median duration of 8 months (inter-quartile range 7-10 months). The numbers of eyes where CSFT had increased ≥ 25 µm, reduced ≥ 25 µm, or remained unchanged were 16 (16%), 6 (6%), and 74 (76%), respectively. Patients with hemoglobin A1c ≥ 8.5% were 5.7 times more likely to develop central subfield thickening (95% CI 1.1-30.1, P = 0.038). CONCLUSIONS: Majority of eyes with DME on OCT had stable CSFT without treatment over a median duration of 8 months. Hemoglobin A1c may be useful for risk stratification.

High myopia and cataract surgery.

PURPOSE OF REVIEW: Cataract surgery in high myopes is challenging. Using third-generation intraocular lens (IOL) formulas, without adjustments, hyperopic refractive outcomes are common. We discuss these issues, focusing on the various lens formulas and transformations that have improved postoperative accuracy. RECENT FINDINGS: Axial length measurement error has been largely overcome by the use of optical interferometry. Despite this, consistent hyperopic errors are still reported. We reviewed the postoperative refraction results compared with the predicted refractions using: standard formulas (Holladay 1, SRK/T, Hoffer Q, and Haigis) with manufacturers' optical lens constants, the User Group for Laser Interference Biometry (ULIB) constants, manufacturers' constants with axial length adjustment method, and fourth-generation IOL formulas (Barrett Universal II, Holladay 2, and Olsen). SUMMARY: Improved predictive results is obtained with the Barrett Universal II (software constants), Haigis (ULIB), SRK/T, Holladay 2 (software constants), and Olsen (software constants) formulas in eyes with axial lengths greater than 26.0 mm and IOL powers greater than 6.0 D. In eyes with axial lengths greater than 26.0 mm and IOL less than 6.0 D, the Barrett Universal II formula (software constants) and the Haigis (axial length adjusted) and Holladay 1 formulas (axial length-adjusted) should be used.

Age-related macular degeneration phenotypes associated with mutually exclusive homozygous risk variants in CFH and HTRA1 genes.

PURPOSE: To determine age-related macular degeneration (AMD) phenotypes associated with mutually exclusive homozygotic risk variants in rs1061170 (CFH) and rs11200638 (HTRA1). METHODS: Nested case-control study of 2,982 eyes (2,129 control, 809 drusen ≥125 µm, 44 advanced AMD) homozygous for CFH [TT or CC] and HTRA1 [GG or AA] were analyzed using logistic regression and generalized estimating equations specifically regards to homozygous risk variants in one but homozygous no-risk in the other gene. RESULTS: In early AMD, [CFH HTRA1] and [CFH HTRA1] were associated with central drusen (odds ratio [95% confidence interval] = 4.13 [2.97-5.73] and 3.65 [1.88-7.09], respectively). However, only [CFH HTRA1] was associated with central drusen occupying ≥50% area (13.9 [2.97-64.7]). In advanced AMD, [CFH HTRA1] was associated with geographic atrophy (4.04 [1.57-10.4]), whereas [CFH HTRA1] was associated with neovascular AMD (36.5 [8.3-160.9]). In doubly homozygous risk groups [CFH HTRA1], odds ratios were multiplicative. CONCLUSION: Central but not peripheral drusen location was strongly associated with both [CFH HTRA1] and [CFH HTRA1]. Only [CFH HTRA1] was significantly associated with increased central drusen area.

Dietary patterns and their associations with age-related macular degeneration: the Melbourne collaborative cohort study.

OBJECTIVE: To evaluate the association between dietary patterns and age-related macular degeneration (AMD). DESIGN: Food frequency data were collected from Melbourne Collaborative Cohort Study (MCCS) participants at the baseline study in 1990-1994. During follow-up in 2003-2007, retinal photographs were taken and evaluated for AMD. PARTICIPANTS: At baseline, 41514 participants aged 40 to 70 years and born in Australia or New Zealand (69%), or who had migrated from the United Kingdom, Italy, Greece, or Malta (31%) were recruited. Of these, 21132 were assessed for AMD prevalence at follow-up. METHODS: Principal component analysis was used to identify dietary patterns (Factors F1-6) among the food items. Logistic regression was used to assess associations of dietary patterns with AMD. MAIN OUTCOME MEASURES: Odds ratios (ORs) for early stages and advanced AMD in association with dietary patterns. RESULTS: A total of 2508 participants (12.8%) had early stages of AMD, and 108 participants (0.6%) had advanced AMD. Six factors characterized by predominant intakes of fruits (F1); vegetables (F2); grains, fish, steamed or boiled chicken, vegetables, and nuts (F3); red meat (F4); processed foods comprising cakes, sweet biscuits, and desserts (F5); and salad (F6) were identified. Higher F3 scores were associated with a lower prevalence of advanced AMD (fourth vs. first quartile) (OR, 0.49; 95% confidence interval [CI], 0.28-0.87), whereas F4 scores greater than the median were associated with a higher prevalence of advanced AMD (OR, 1.46; 95% CI, 1.0-2.17). CONCLUSIONS: Rather than specific individual food items, these factors represent a broader picture of food consumption. A dietary pattern high in fruits, vegetables, chicken, and nuts and a pattern low in red meat seems to be associated with a lower prevalence of advanced AMD. No particular food pattern seemed to be associated with the prevalence of the earliest stages of AMD.

Is renal function associated with early age-related macular degeneration?

PURPOSE: Age-related macular degeneration (AMD) and chronic kidney disease both involve immune dysregulation and may share underlying pathophysiologic changes to systemic homeostasis. Hence, we aim to evaluate associations between impaired kidney function and early AMD, in a search for urinary biomarkers for AMD. METHODS: A population-based, cross-sectional analysis of persons aged 45 to 84 years was conducted with renal function measured using serum creatinine and cystatin C levels and the estimated glomerular filtration rate (eGFR) calculated. Age-related macular degeneration status was ascertained from retinal photographs. RESULTS: Of 5874 participants, 221 had early AMD. High serum cystatin C and low eGFR (≤60 ml/min/1.73 m) were not associated with early AMD in our multivariate analyses. Among normotensive persons, however, highest versus other deciles of cystatin C were associated with an increased prevalence of early AMD (odds ratio, 1.80; 95% confidence interval, 1.00 to 3.23). CONCLUSIONS: Results could not confirm an association between kidney function and early AMD. The borderline association between cystatin C and early AMD in normotensive persons require further verification.

Polygenic Prediction of Keratoconus and its Measures: Cross-Sectional and Longitudinal Analyses in Community-Based Young Adults.

AIM: This study evaluates the performance of a multitrait polygenic risk score (PRS) in an independent cohort to predict incident or progression of keratoconus. DESIGN: Prospective cross-sectional and cohort study METHODS: Setting: Single-center; Study population: 1478 community-based young adults (18-30 years; 51% female), including 609 (52% female) who returned for an 8-year follow-up; Observation procedures: Scheimpflug imaging (Pentacam, Oculus), genotyping and development of a multitrait PRS previously validated to predict keratoconus in older adults.; Main outcome measure: Belin/Ambrόsio enhanced ectasia display (BAD-D) score and keratoconus, defined as BAD-D ≥2.6, were each analyzed against the PRS using linear and logistic regression, respectively. RESULTS: Prevalence of keratoconus was 2.5% (95% confidence interval [CI] = 1.9-3.6) in the cross-sectional cohort. Each z-score increase in PRS was associated with worse BAD-D z-score by 0.13 (95%CI = 0.08-0.18) and 1.6 increased odds of keratoconus. The 8-year keratoconus incidence was 2.6% (95%CI = 1.3-4.0). Participants in the highest PRS decile were more likely to have incident keratoconus compared to the rest of the cohort (odds ratio = 3.85, 95%CI = 1.21-12.22). For each z-score increase in PRS, 8-year change in BAD-D z-score worsened by 0.11 (95%CI = 0.04-0.17). CONCLUSIONS: A PRS for keratoconus could be useful in predicting incident keratoconus and progression, demonstrating its potential utility in clinical settings to identify patients at high risk of postsurgery ectasia or those who may benefit most from keratoconus intervention.

The prevalence and risk factors of epiretinal membranes: the Melbourne Collaborative Cohort Study.

PURPOSE: To determine the prevalence of epiretinal membranes (ERMs) in Melbourne, Australia and its risk factors in this population. METHODS: The Melbourne Collaborative Cohort Study is a prospective study investigating the role of diet and life style in the causation of common chronic diseases. Eighty-six percent of participants were of Northern European origin born in Australia or United Kingdom and 14% were migrants from Greece or Italy (Southern European origin). Nonmydriatic digital retinal photography was implemented at Melbourne Collaborative Cohort Study follow-up. The ERMs were recorded as cellophane macular reflex without retinal folds or preretinal macular fibrosis (PMF) with retinal folds. RESULTS: A total of 22,406 participants had retinal photography, 95% (n = 21,241) were eligible for ERM grading. The ERM prevalence were 8.9% (1,882); cellophane macular reflex, 4.9% (1,047); and preretinal macular fibrosis, 3.9% (835). After adjustment for age, sex, level of education, smoking status, level of cholesterol, body mass index, waist-to-hip ratio, waist measurement, blood pressure, diabetes, and stroke, increasing age and Southern European ethnicity was significantly associated with ERMs. Overall, in Southern Europeans, ERMs odd ratio was 1.97 (95% confidence intervals, 1.67-2.31), P < 0.001; preretinal macular fibrosis was 1.82 (95% confidence intervals, 1.43-2.31), P < 0.001; and cellophane macular reflex was 1.93 (1.57-2.38), P < 0.001. CONCLUSION: In an older Australian population, the prevalence of ERMs was 8.9% and was almost two times higher in participants of Southern European origin than Northern European origin.

FROSTED BRANCH ANGIITIS ASSOCIATED WITH MIXED CONNECTIVE TISSUE DISEASE.

PURPOSE: To present a case of frosted branch angiitis associated with an exacerbation of mixed connective tissue disease (MCTD). METHODS: Single case report. RESULTS: A 31-year-old woman presented with a flare of her long-standing MCTD after a change in her immunosuppressive medications. She developed blurred vision and floaters first in the left eye but eventually in both eyes. Fundoscopy showed patchy perivascular sheathing of tertiary branch venules surrounded by retinal hemorrhages characterized as frosted branch angiitis. The patient's MCTD symptoms and retinal vasculitis improved with continued immunosuppressive therapy. At 1-month follow-up, her visual acuity had improved to 20/20 bilaterally with complete resolution on fundoscopy. CONCLUSION: To the authors' knowledge, this is the first report of frosted branch angiitis seen in association with MCTD. The improvement in the patient's visual acuity and fundoscopic findings in this case supports the role of immunosuppressive therapy to treat secondary frosted branch angiitis associated with an autoimmune condition such as MCTD. However, it is recommended that a comprehensive medical workup is performed to exclude an infective cause, particularly in immunocompromised patients.

20/20--Alcohol and age-related macular degeneration: the Melbourne Collaborative Cohort Study.

Little evidence exists regarding associations between age-related macular degeneration (AMD) and moderate alcohol consumption, patterns of consumption, or different types of alcoholic beverage. The authors examined associations between AMD prevalence and alcohol intake using 20,963 participants from the Melbourne Collaborative Cohort Study aged 40-69 years at baseline (1990-1994). Participants' alcohol consumption was determined from a structured interview at baseline. At follow-up from 2003 to 2007, digital macula photographs of both eyes were taken and evaluated for early and late AMD signs. Drinking more than 20 g of alcohol per day was associated with an approximate 20% increase in the odds of early AMD (odds ratio = 1.21, 95% confidence interval: 1.06, 1.38; P = 0.004) when compared with those who reported no alcohol intake at baseline, having adjusted for sex, age, smoking, country of birth, education, physical activity, and energy from food. This positive association was apparent for wine, beer, and spirits. The estimates were similar for both sexes. The odds ratio for those drinking more than 20 g of alcohol per day for late AMD was 1.44 (95% confidence interval: 0.85, 2.45; P = 0.17). These results show a modest association between alcohol consumption and increased AMD risk.

Diagnosis and Management of Keratoconus-A Narrative Review of Clinicians' Perspectives.

This review discusses the current practices, attitudes, and trends in diagnosing and managing keratoconus (KC) in adults and children by optometrists and ophthalmologists in order to highlight the differences on a global scale. Two independent reviewers searched the electronic databases and grey literature for all potential articles published from 1 January 2000 to 1 June 2022 on management of KC. Keywords used in searches included "keratoconus", "diagnosis", "management", "treatment", "attitude", "practices", "opinion", "optometrist", "ophthalmologist", "consensus", and "protocol". A total of 19 articles was included in this review-12 from the database search and seven from the grey literature. Although a common stepwise approach of non-surgical management was noted, there were differences in the rates of prescribing rigid gas permeable lenses. Furthermore, while clinicians agreed on the need for early diagnosis, the timeline and type of referral varied significantly. A similar discordance was found in the milestones for surgical intervention and preferred surgical techniques. Practice patterns in keratoconus diagnosis and management vary throughout the world. Multiple recommendations and suggestions to minimise the differences have been provided in the literature, with the main themes being improvement in education, interdisciplinary patient care, and further research to reach consensus.

Cross-Linking Improves the Quality of Life of People With Keratoconus: A Cross-Sectional and Longitudinal Study From the Save Sight Keratoconus Registry.

PURPOSE: The purpose of this study was to comprehensively evaluate the patient-reported quality-of-life (QoL) outcomes after corneal cross-linking for keratoconus. METHODS: This Save Sight Keratoconus Registry study used cross-sectional and longitudinal designs. For the cross-sectional study, 532 patients with keratoconus (mean age 30.9 ± 11.9 years; 31.6% female) completed the Keratoconus Outcomes Research Questionnaire (KORQ) and 343 patients with keratoconus (mean age 28.3 ± 10.7 years; 32.7% female) completed the Impact of Vision Impairment (IVI) questionnaires. Similarly, for the longitudinal study, 39 patients (mean age 24.2 ± 8.4 years; 23.1% female) completed the KORQ and 16 patients (mean age 27.9 ± 17.1 years; 50.0% female) completed the IVI questionnaire before and after 6 months of cross-linking. The QoL data were analyzed using the Andrich Rating Scale Model of Rasch analysis. RESULTS: For both cross-sectional and longitudinal studies, the KORQ and IVI scales demonstrated satisfactory psychometric properties [ordered and well-spaced categories, variance explained by the measure 52%-73%, person separation index 2.4-3.9, and fit statistics <1.3 (most cases)]. The patients who had not undergone corneal cross-linking had worse mean activity limitation than those with cross-linking (P = 0.008). However, the differences in symptoms and emotional scores between the groups were not statistically significant (both P > 0.05). The longitudinal study showed that cross-linking was associated with improved activity limitation, symptoms, and emotional scores. CONCLUSIONS: The KORQ and IVI are psychometrically robust tools to evaluate the QoL outcomes of corneal cross-linking. Cross-linking is associated with improved activity limitation, symptoms, and emotional status.