Vision Eye Institute

Transient pain and ocular inflammation may occur with ophthalmic surgery. Pain is an important determinant of patient satisfaction, and inflammation can increase the risk for suboptimal visual outcomes. Topical anti-inflammatory therapies can reduce the incidence of postoperative pain and inflammation but have many limitations, including nonadherence and significant potential side effects such as cataract formation and intraocular pressure elevation. There is unmet need for a therapy that provides anti-inflammatory and analgesic activity while overcoming the limitations of topical therapy. The intracanalicular dexamethasone insert (DEX) overcomes many of the limitations of topical therapy. DEX is a fluorescent yellow cylindrical-shaped polyethylene glycol-based hydrogel insert incorporating 0.4mg preservative-free dexamethasone. The insert was designed based on human anatomy and measurements of the canalicular system and continuously releases a tapered dose of dexamethasone over approximately 30days onto the surface of the eye. The insert is completely resorbable and does not require removal. DEX was approved by the US Food and Drug Administration for the treatment of pain (in 2018) and inflammation (in 2019) following ocular surgery; in 2021, the treatment of ocular itching associated with allergic conjunctivitis was added as an indication. We present a comprehensive review of the current therapeutic landscape for management of postoperative pain and inflammation following cataract surgery, including the limitations of topical eye drop medications. We review data from the key phase2 and 3 clinical trials that supported the approval and label expansion for DEX. We also summarize the broader literature of smaller studies evaluating the role of DEX in controlling postoperative pain and inflammation for a variety of ophthalmic surgery beyond cataract surgery as well as in management of ocular itching associated with allergic conjunctivitis.

PurposePharmacodynamic biomarkers of sirolimus were investigated using omics analysis of tear fluids from Japanese patients with meibomian gland dysfunction (MGD).MethodsIn a Phase 2a trial, sirolimus or vehicle eyedrops were administered twice daily for 12 weeks. Tear samples from 29 patients (15 sirolimus, 14 vehicle) were collected pre- and post-treatment. LC-MS/MS-based proteomics and lipidomics were performed. Within-group changes were analyzed, followed by differential expression and pathway analysis. Key candidates were evaluated using estimation plots (Registration ID: UMIN000049186).ResultsOver 3000 proteins and 55 lipids were quantified. mTOR signaling components (ATP6V1D, RRAGC, DEPTOR) were significantly modulated. ATP6V1D showed a significant decrease in the sirolimus group (p = 0.0024), but not in the vehicle group (p = 0.528). Lipids 12-HETE and 13-HpODE significantly increased post-treatment in the sirolimus group.ConclusionResults suggested that sirolimus inhibited the mTOR pathway. ATP6V1D, 12-HETE, and 13-HpODE were suggested to be pharmacodynamic biomarkers for sirolimus. These findings may facilitate pharmacodynamic monitoring of mTOR-targeted therapies for ocular surface disorders.

The macula is a pigmented area located at the centre of the retina, responsible for central, high-resolution colour vision. Previous research has demonstrated that oral carotenoid supplementation can enhance contrast sensitivity (CS) in European populations. This study aims to investigate whether carotenoid supplementation can also improve visual function in the Chinese population. The Contrast Sensitivity Vision (CSV) trial is a double-blind, randomised controlled trial conducted at the Zhongshan Ophthalmic Center in Guangzhou, China. 220 eligible Chinese adults will be randomised in a 1:1 ratio to receive either oral supplementation of 10 mg lutein, 10 mg meso-zeaxanthin and 2 mg zeaxanthin in a formula-based oil suspension (administered as one soft gel capsule) or a placebo oil soft gel capsule daily for 1 year. Participants in both groups will undergo ophthalmological study procedures including best-corrected visual acuity (BCVA), contrast sensitivity, optical coherence tomography, fundus photography and skin carotenoid examinations at baseline and at 3-month, 6-month and 12-month follow-up visits. Blood tests and a Dietary Carotenoid Screening Questionnaire will be administered at baseline and at the 12-month follow-up. Subjective visual function questionnaire interviews will be administered at baseline and at the 3-month, 6-month and 12-month follow-ups. The primary outcome will assess change in CS at 6 cycles per degree (cpd) over the 1-year study intervention. Secondary outcomes will examine CS at 6 cpd at the 3-month and 6-month follow-up, CS at other cpd, BCVA, subjective visual function and skin carotenoid levels as measured at baseline, 3-month, 6-month and 12-month follow-ups. The CSV trial was approved by the Ethics Committee of the Zhongshan Ophthalmic Center, Guangzhou, China (No. KYPJ141-4). Participants will have the opportunity to ask questions about the trial, and written informed consent will be obtained from all participants prior to their involvement in the study. Results will be disseminated through peer-reviewed publication and conference presentations. NCT06098677.

Transient flickering light stimulation (FLS) was previously demonstrated to enhance both retinal blood flow (RBF) and full-field electroretinogram (ffERG) responses in wild-type mice. This study aimed to investigate the effects of acute ocular hypertension (AOH) on these flicker-induced changes in mice. Adult C57BL6J mice were randomly divided into three groups: the AOH, sham, and naïve groups. All animals underwent the following measurements, including scotopic and photopic ffERGs (pre- and post-12 hertz [Hz] FLS), optical coherence tomography (OCT), and Doppler OCT (pre- and post-12Hz FLS), at baseline (day 0), day 16, and day 43. On day 8, intraocular pressure (IOP) was elevated to 80 millimeters of mercury (mm Hg) in the AOH group or maintained at 15mm Hg in the sham group for 1hour. The naïve group received no intervention. Transient FLS significantly enhanced both RBF and photopic b-wave amplitudes in all three groups at day 0 (baseline). The AOH group showed significant reductions in the positive scotopic threshold responses and both inner and middle retinal layer thicknesses at days 16 and 43. Significant flicker-induced increases in RBF and b-wave amplitudes were observed in the sham and naïve groups at days 16 and 43. However, significant reductions in flicker-induced enhancements of RBF and b-wave amplitude were observed in the AOH group at days 16 and 43 compared with the sham and naïve groups. Flicker-induced enhancements in RBF and electro-retinal responses were impaired by AOH. This impairment suggests that the retinal functional hyperemia is sensitive to IOP elevation.

This meta-analysis aims to determine the clinical manifestations, prevalence, and risk factors of asthenopia across diverse populations. We systematically searched PubMed up to April 2024 for studies published within the last five years on asthenopia, without language or design restrictions. Reference lists were also reviewed. The study quality was evaluated using the Newcastle-Ottawa Scale. A random-effects meta-analysis was conducted to calculate proportions, prevalence rates, odds ratios (ORs) and their 95% confidence intervals (CIs). Overall, 63 studies were included. The pooled prevalence of asthenopia detected via questionnaires or symptom report was 51% (95% CI = 50%, 52%). Subgroup analyses showed high prevalence among digital device users (90%) and computer workers (77%). During the COVID-19 pandemic, prevalence rose among adults (39%-45%), university students (36%-57%), and school-aged children (45%-64%). The most frequent ocular symptoms were eye tiredness (65%, 95% CI = 46%, 84%), eye strain (47%, 95% CI = 37%, 58%), and burning/irritation (43%, 95% CI = 35%, 51%). Musculoskeletal symptoms, including neck pain (45%, 95% CI = 28%, 62%) and shoulder pain (30%, 95% CI = 12%, 48%) were also prevalent. Neuropsychological symptoms included headache (50%, 95% CI = 41%, 59%) and difficulty concentrating (44%, 95% CI = 32%, 56%). Risk factors included short sleep duration (OR = 1.28; 95% CI = 1.04, 1.57), prior eye disease (OR = 2.59; 95% CI = 1.43, 4.69), prolonged screen time (OR = 1.15; 95% CI = 1.09, 1.21), and ambient conditions like air conditioning use (OR = 23.02; 95% CI = 4.94, 107.18). Protective measures included anti-glare filters (OR = 0.34; 95% CI = 0.19, 0.64), regular breaks (OR = 0.21; 95% CI = 0.09, 0.51), and computer use knowledge (OR = 0.20; 95% CI = 0.13, 0.30). Asthenopia is prevalent across diverse populations, characterised by a wide range of symptoms and influenced by modifiable risk factors. Our findings support a unified definition to improve clinical recognition and offer preliminary evidence to help shape future research on preventive strategies. PROSPERO: CRD42024536841.

To compare the anatomical and functional outcomes of internal limiting membrane (ILM) flap and conventional ILM peeling in idiopathic full-thickness macular holes (FTMHs). Retrospective cohort study of all eyes treated with vitrectomy and ILM peeling (ILM-P) with or without ILM flap (ILM-F) for primary idiopathic FTMH repair in the Australian and New Zealand Society of Retinal Specialists (ANZSRS) Registry between 2006 and 2023. Propensity score weighting and multivariable regression analysis adjusted for baseline characteristics and covariates, including surgeon grade, lens status, and follow-up duration, were used to evaluate hole closure rate and best corrected visual acuity (BCVA) change at 3 months. Two thousand nine hundred ninety eyes of 2905 patients were included (mean age 69 ± 9 years). One Hundred Ninety-nine eyes underwent ILM-F and 2871 underwent ILM-P. On weighted multivariable regression analysis, ILM-F showed higher odds of hole closure compared to ILM-P (OR = 2.97, 95% CI: 1.08-8.20, p = 0.04). The adjusted closure rate was > 95% across all hole sizes in the ILM-F group, while only falling below 90% for X-large + holes (> 550 μm) in the ILM-P group. No significant difference in BCVA gain was observed between the two groups at 3 months (p = 0.08). The effects of ILM-F compared to ILM-P were consistent across all hole sizes. Although the ILM-F technique was more effective in idiopathic FTMH closure, visual acuity outcomes were comparable to conventional ILM peeling. These findings suggest that ILM-F is not required for the treatment of small and medium FTMHs.

PurposeOuter retinal band integrity strongly predicts late age-related macular degeneration (AMD), however, it is often assessed subjectively and vulnerable to intergrader variability. This study quantifies retinal pigment epithelium (RPE) sinuosity from automated segmentations of a commercially available optical coherence tomography (OCT) and its ability to predict late AMD.MethodsConsecutive patients with intermediate AMD who progressed to late disease (n = 69) or remained stable (n = 198) were recruited. Outer retinal band integrity was measured quantitatively using RPE sinuosity, calculated as the ratio of RPE:RPE-fit line length across macular B-scans. RPE sinuosity was measured in the foveal B-scan alongside the mean, maximum, and median values across the five central B-scans. The RPE and ellipsoid zone (EZ) continuity was graded qualitatively, as well as other AMD biomarkers currently used for prognostication. Adjusted odds ratios for progression were calculated for each variable.ResultsMean follow-up time was 3.15 years (1.93 years). Pigmentary abnormalities (P = 0.001), subretinal drusenoid deposits (SDDs; P > 0.0001), drusen volume (P = 0.01), and late AMD in the fellow eye (P = 0.001) were present in a higher proportion of progressor than stable eyes at baseline. Median RPE sinuosity was the strongest predictor of progression within 5 years (2.52 [1.14–5.55]) and across the study period (2.35 [1.25–4.43]). No qualitative measures could predict late AMD within any time frame.ConclusionsRPE sinuosity outperformed qualitative outer retinal band integrity assessments for late AMD prediction and is a reliable, repeatable evaluation method. Verifying these results using different OCT devices in a prospective cohort is needed to determine whether the feature can enhance late AMD risk models and improve clinical management.

To develop a model investigating the effects of the psychometric function's slope and lapse rate on QUEST visual acuity (VA) thresholds for preschool children. Monte Carlo simulations of QUEST (16 trials) measurements of VA were performed using an underlying ideal observer model for a range of Ideal Thresholds, Slopes, and Lapse Rates for 10- and 4-alternative forced choices (AFC). Ideal Slopes (in probit size) were varied from steep to flat, 0.05 to 0.20 logMAR. Ideal Lapse Rates were varied from 0.01 to 0.50 (at Ideal Probit Size of 0.10 logMAR). Thresholds were estimated using three different techniques: (i) QUEST's maximum likelihood estimate (75% correct), and probit analysis of logMAR value (55% correct) with (ii) fixed-slope probit (probit size=0.10 logMAR) or (iii) floating-slope probit (probit size=0.02-0.29 logMAR). An index, Gain-Corrected Standard Deviation, was developed to assess how sensitive a technique was for detecting a change in VA. A smaller Gain-Corrected Standard Deviation indicates a technique is more sensitive to change. Measured VA thresholds from QUEST, floating-slope probit, and fixed-slope probit are linearly related to Ideal Threshold from -0.20 to 0.80 logMAR. Flat slopes and higher lapse rates result in an increased Gain-Corrected Standard Deviation for all threshold measurement techniques (higher when thresholds were estimated with probit fitting than with QUEST Maximum likelihood), with the increase in Gain-Corrected Standard Deviation being slightly higher for 4AFC compared to 10AFC across the range of Ideal Slopes and Lapse Rates. For 4AFC, the Gain-Corrected Standard Deviation range for varied lapse rates (0.01-0.50) was QUEST, 0.062-0.567; floating-slope probit, 0.079-0.623; and fixed-slope probit, 0.079-0.626 logMAR. QUEST maximum likelihood outputs should be used instead of fitting probit functions in preschool children when there are limited numbers of trials. Flat slopes and high lapse rates can significantly decrease the precision of QUEST estimates of VA in preschool children.

To quantify determinants of intergrader agreement for key retinal photography and optical coherence tomography (OCT) biomarkers in early to intermediate age-related macular degeneration (AMD) and to inform future consensus definitions and grading protocol. Single eyes from 269 participants with early to intermediate AMD were consecutively sampled. Retinal photographs were evaluated for the presence of large drusen and pigmentary abnormalities. OCT B-scans were graded for reticular pseudodrusen (RPD), outer retinal band abnormality (external limiting membrane [ELM], ellipsoid zone [EZ], and retinal pigment epithelium [RPE]), nascent geographic atrophy (nGA), intraretinal hyperreflective foci (IHRFs), hyporeflective drusen cores (hDCs), shallow irregular RPE elevations (SIREs), and drusenoid pigment epithelial detachment (DPED). Biomarkers were classified using a trinary certainty system: "definitely present" (≥90%), "questionably present" (50%-90%), or "absent" (<50%). The main outcome was odds of intergrader agreement from generalized estimating equations adjusting for intraparticipant correlations, biomarker type, and eye- and participant-level factors. Odds of agreement were comparable for large drusen, nGA, RPE abnormality, IHRF, and ELM abnormality; higher for RPD (odds ratio [95% confidence interval], 3.17 [1.56-6.45], P < 0.01); and lower for SIRE, EZ abnormality, pigmentary abnormalities, hDC, and DPED (up to 0.5 [0.32-0.78], P < 0.01). Agreement improved with higher grading certainty (1.4 [1.22-1.6], P < 0.0001) but declined with age (per decade, 0.8 [0.7-0.93], P < 0.01). Biomarker type, grading certainty, and participant age influence OCT agreement. Consensus definitions and grading protocols, including the use of high certainty thresholds (≥90%), may improve consistency. Implementing consensus definitions and protocols can improve agreement and strengthen the clinical utility of OCT biomarkers in AMD.