Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial.

PURPOSE: This study aimed to assess the safety, tolerability, and potential efficacy of topical elamipretide in patients affected with Leber hereditary optic neuropathy (LHON). DESIGN: This phase II, prospective, randomized, vehicle-controlled, single-center clinical trial involved administration of elamipretide 1% topical ophthalmic solution to patients with LHON over a 52-week double-masked treatment period, followed by an open-label extension (OLE) for up to 108 additional weeks of treatment. PARTICIPANTS: Twelve patients with LHON were included in this study. Patients aged 18 to 50 years with decreased vision for at least ≥ 1 year and ≤ 10 years, and a genetically confirmed diagnosis of m.11778G>A LHON were eligible for this trial. METHODS: For the first 52 weeks of the study, patients were randomized to 1 of 3 groups: elamipretide in both eyes or elamipretide in 1 eye (left eye and right eye were considered separate groups) and vehicle in the other eye, followed by an OLE in which both eyes were treated with elamipretide. MAIN OUTCOME MEASURES: The primary outcome measure was assessment of adverse events (AEs) from the administration of topical elamipretide, and the primary efficacy end point was change in best-corrected visual acuity (BCVA). Secondary outcome measures included changes in color vision, visual field mean deviation, and electrophysiological outcomes. RESULTS: Elamipretide was well tolerated with the majority of AEs being mild to moderate and resolving spontaneously. The change from baseline in BCVA in elamipretide-treated eyes was not significantly different from the vehicle eyes at any time point. Six of 12 subjects met the criteria for clinically relevant benefit (CRB). In the post hoc analysis, change from baseline in mean deviation in the central visual field was significantly greater in elamipretide-treated eyes versus the vehicle eyes. Compared with baseline, both treatment groups showed improvement in color discrimination and contrast sensitivity in the OLE. CONCLUSIONS: Elamipretide treatment was generally well tolerated, with no serious AEs reported. Although this study did not meet its primary BCVA efficacy end point, improvements across assessments on visual function during the OLE and the post hoc findings of the Humphrey automated visual field central region were encouraging and require further exploration. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Visual Acuity Outcomes and Complications after Intraocular Lens Exchange: An IRIS® Registry (Intelligent Research in Sight) Analysis.

PURPOSE: To assess risk factors for worse visual acuity (VA) outcomes after intraocular lens (IOL) exchange, and the most common postsurgical complications. DESIGN: Retrospective cohort study. PARTICIPANTS: Eyes from patients 18 years of age and older in the IRIS® Registry (Intelligent Research in Sight) that underwent IOL exchange in the United States between 2013 and 2019. METHODS: Vision improvement compared with baseline was determined at 1 year after surgery. A multivariable generalized estimating equation model adjusting for demographic factors and baseline vision was used to identify factors associated with VA worse than 20/40 at 1 year. MAIN OUTCOME MEASURES: Visual outcomes and postoperative complications after lens exchange. RESULTS: A total of 46 063 procedures (n = 41 925 unique patients) were included in the analysis. Overall, VA improved from a mean ± standard deviation (SD) of 0.53 ± 0.58 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/70) before surgery to a mean ± SD of 0.31 ± 0.40 logMAR (Snellen equivalent, 20/40) at 1 year. Among eyes with VA recorded at both baseline and 1 year after surgery, 60.5% achieved VA of 20/40 or better at 1 year. Vision of worse than 20/40 at 1 year was associated with greater age (odds ratio [OR], 1.16 per 5-year increase; 95% confidence interval [CI], 1.14-1.18) and higher logMAR baseline VA (OR, 1.14 per 0.1-logMAR increase; 95% CI, 1.14-1.15), as well as Black or African American (OR, 1.96; 95% CI, 1.68-2.28), Hispanic (OR, 1.82; 95% CI, 1.59-2.08), and Asian (OR, 1.48; 95% CI, 1.21-1.81) race or ethnicity versus White race, Medicaid (OR, 1.78; 95% CI, 1.40-2.25) versus private insurance, smoking history (OR, 1.22; 95% CI, 1.11-1.35), and concurrent anterior (OR, 1.65; 95% CI, 1.51-1.81) and posterior (OR, 1.53; 95% CI, 1.41-1.66) vitrectomy versus no vitrectomy. Female sex was associated with better VA at 1 year. At 1 year, epiretinal membrane (10.9%), mechanical lens complication (9.4%), and dislocation of the replacement lens (7.1%) were the most common complications. CONCLUSIONS: In this large national cohort, the annual number of IOL exchanges rose steadily over time. Vision improved in 60.2% of patients; worse visual outcomes were associated with greater age, worse baseline vision, Black race, Hispanic ethnicity, Medicaid insurance, smoking, and concurrent vitrectomy. Epiretinal membrane was the most common complication. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy of Faricimab versus Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase III YOSEMITE and RHINE Trials.

PURPOSE: Diabetic Retinopathy Clinical Research Network Protocol T suggests that the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME and baseline BCVA of 20/50 or worse enrolled in faricimab phase III trials. DESIGN: YOSEMITE and RHINE were identically designed, multicenter, randomized, double-masked, active comparator-controlled, noninferiority trials. PARTICIPANTS: Adults ≥18 years of age with center-involving macular edema secondary to type 1 or 2 diabetes. METHODS: Patients were randomized to faricimab every 8 weeks (Q8W), faricimab personalized treat-and-extend (T&E) regimen, or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intention-to-treat population with baseline BCVA of 20/50 or worse. MAIN OUTCOME MEASURES: Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. RESULTS: In YOSEMITE and RHINE, respectively, 220 and 217 patients in the faricimab Q8W arm, 220 and 219 patients in the faricimab T&E arm, and 219 and 214 patients in the aflibercept Q8W arm showed baseline BCVA of 20/50 or worse. In both trials, mean change in ETDRS BCVA was comparable between treatments across trials at years 1 and 2. In YOSEMITE, adjusted mean change from baseline in CST (µm) at year 1 was greater with faricimab Q8W (-232.8; P < 0.0001) and faricimab T&E (-217.4; P = 0.0004) ) versus aflibercept Q8W (-190.4). In RHINE, this was faricimab Q8W (-214.2; P = 0.0006) and faricimab T&E (-206.6; P = 0.0116) versus aflibercept Q8W (-186.6). In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. The median time to first CST of <325 µm and first absence of intraretinal fluid was shorter in the faricimab arms versus the aflibercept arm, with fewer injections on average. CONCLUSIONS: In patients with DME and baseline ETDRS BCVA of 20/50 or worse, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Concordance between Self-Reported Visual Difficulty and Objective Visual Impairment: The National Health and Aging Trends Study.

PURPOSE: To examine the performance of self-reported visual difficulty (VD) in predicting objective visual impairment (VI) in older adults and explore factors that influence discordance. DESIGN: Cross-sectional analysis of the National Health and Aging Trends Study (2022). METHODS: Participants reporting blindness or difficulties with distance or near vision were characterized as having VD. Presenting binocular distance visual acuity (VA), near VA, and contrast sensitivity (CS) were assessed. Objective VI was defined as having VI in distance VA (worse than 20/40), near VA (worse than 20/40), or CS (worse than 1.55 logCS). Receiver operating characteristic analysis was used to compare performance of VD in predicting VI. To investigate factors that influence discordance, we limited our sample to adults with VI and used a multivariable logistic regression model to identify factors associated with not reporting VD. Similar analyses were performed to explore factors associated with reporting VD in adults without VI. MAIN OUTCOME MEASURES: Discordance factors. RESULTS: Four thousand nine hundred ninety-nine adults were included in the 2022 cohort. Visual difficulty achieved an area under the curve (AUC) of 56.0 (95% confidence interval [CI], 55.2-56.9) in predicting VI, with a sensitivity of 15.8 (95% CI, 14.2-17.5) and specificity of 96.3 (95% CI, 95.5-96.9). Characteristics associated with not reporting VD in adults with VI included female gender (odds ratio [OR], 0.64 [95% CI, 0.42-0.99]), Hispanic ethnicity (OR, 0.49 [95% CI, 0.31-0.78), higher income (≥75 000, OR, 1.99 [95% CI, 1.14-3.45]), ≥4 comorbidities (OR, 0.46 [95% CI, 0.29-0.72]), and depressive symptoms (OR, 0.49 [95% CI, 0.25-0.93]). Factors associated with self-reporting VD in the absence of VI included Hispanic ethnicity (OR, 2.11 [95% CI, 1.15-3.86]), higher income (≥$75 000, OR, 0.27 [95% CI, 0.12-0.63]), and anxiety symptoms (OR, 3.05 [95% CI, 1.56-5.97]). CONCLUSIONS: Self-reported VD is a distinct measure assessing disability and has limited ability in predicting objective VI. Caution is advised when using self-reported VD as a surrogate measure for objective VI in epidemiological studies, although it may still be an effective way to capture risk of current or future disability. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Facedown Positioning in Macular Hole Surgery: A Systematic Review and Individual Participant Data Meta-Analysis.

TOPIC: To assess the anatomical and visual effects of facedown positioning (FDP) advice in patients undergoing vitrectomy with gas tamponade for idiopathic full-thickness macular holes (FTMHs), and to explore differential treatment effects by macular hole size and FDP duration. CLINICAL RELEVANCE: The necessity and duration of FDP for FTMH closure remain contentious, with no consensus guidelines. METHODS: Prospectively registered systematic review and individual patient data (IPD) meta-analysis of randomised controlled trials comparing FDP to no FDP (nFDP) across the MEDLINE, Embase, and Cochrane Library databases and clinical trial registries from January 2000 to March 2023 (CRD42023395152). All adults with idiopathic FTMHs undergoing vitrectomy with gas tamponade were included. The main outcomes were primary macular hole closure and post-operative visual acuity at 6 months or nearest time point. RESULTS: Of 8 eligible trials, 5 contributed IPD for 379 eyes and were included in our analysis. The adjusted odds ratio (OR) for primary closure with FDP versus nFDP was 2.41 (95% CI 0.98 to 5.93, P = 0.06) [GRADE: Low], translating to a relative risk (RR) of 1.08 (1.00 to 1.11) and a number needed to treat (NNT) of 15. The FDP group exhibited a mean improvement in post-operative visual acuity of -0.08 logMAR (-0.13 to -0.02, P = 0.006) [GRADE: Low] compared to the nFDP group. Benefits were more certain in participants with larger holes of minimum linear diameter ≥ 400 µm: adjusted OR for closure ranged from 1.13 to 10.12 (P = 0.030) (NNT 12), with a mean visual acuity improvement of -0.18 to -0.01 logMAR (P = 0.022). Each additional day of FDP was associated with improved odds of anatomical success (adjusted OR 1.02 to 1.41, RR 1.00 to 1.02, P = 0.026) and visual acuity improvement (-0.02 logMAR, -0.03 to -0.01, P = 0.002), possibly plateauing at 3 days. CONCLUSION: This study provides low certainty evidence that FDP improves the anatomical and visual outcomes of macular hole surgery modestly and indicate that the effect may be more substantial for macular holes exceeding 400 µm. The findings support recommending FDP for patients with macular holes exceeding 400 µm pending further investigation.

Assessment of Visual Function with Cotoretigene Toliparvovec in X-Linked Retinitis Pigmentosa in the Randomized XIRIUS Phase 2/3 Study.

PURPOSE: Cotoretigene toliparvovec (BIIB112/AAV8-RPGR) is an investigational vector-based gene therapy designed to provide a full-length, codon-optimized retinitis pigmentosa GTPase regulator (RPGR) protein to individuals with RPGR-associated X-linked retinitis pigmentosa (XLRP). We assessed efficacy and tolerability of cotoretigene toliparvovec subretinal gene therapy. DESIGN: Part 2 of the XIRIUS trial (ClinicalTrials.gov identifier, NCT03116113) was a phase 2/3, 12-month, randomized (1:1:1) dose-expansion study. PARTICIPANTS: Male patients ≥10 years of age with RPGR-associated XLRP were included. METHODS: Participants were randomized 1:1:1 to receive low-dose subretinal cotoretigene toliparvovec (5 × 1010 vector genomes/eye), high-dose cotoretigene toliparvovec (2.5 × 1011 vector genomes/eye) or to be an untreated control participant. MAIN OUTCOME MEASURES: The primary end point was the percentage of participants meeting microperimetry responder criteria (≥ 7-dB improvement at ≥ 5 of 16 central loci). Secondary end points included change from baseline in retinal sensitivity at the central 16 loci and the entire 68 loci at 12 months and change from baseline in low-luminance visual acuity (LLVA) at 12 months, as well as the proportion of eyes with a ≥ 15-Early Treatment Diabetic Retinopathy Study ETDRS letter LLVA and ≥ 10-ETDRS letter LLVA change from baseline at month 12. RESULTS: Because of the impact of the COVID-19 pandemic, enrollment ended before reaching the initial target, leaving the trial underpowered. Twenty-nine participants were included (low-dose group, n = 10; high-dose group, n = 10; control group, n = 9). At month 12, the percentage of participants meeting microperimetry responder criteria was not significantly different between either cotoretigene toliparvovec group (low dose, 37.5% [P = 0.3181]; high dose, 25.0% [P = 0.5177]) and the control group (22.2%). However, the mean change from baseline in microperimetry sensitivity improved significantly with the low-dose group versus the control group at month 12 (P = 0.0350). Significant improvement in LLVA occurred in the low-dose group versus the control group at month 12 (33.3% difference [80% confidence interval, 14.7%-55.2%]; P = 0.0498). Three ocular-related serious adverse events (SAEs) occurred in the low-dose group versus 7 SAEs in the high-dose group. CONCLUSIONS: The primary microperimetry end point was not met. Significant improvements in LLVA and mean microperimetry were observed compared with controls and fewer SAEs occured with low-dose compared with high dose cotoretigene toliparvovec. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Pituitary deficiencies related to optic nerve hypoplasia and visual acuity.

OBJECTIVE: Optic nerve hypoplasia (ONH), the congenital underdevelopment of the optic nerve, is an increasing cause of visual impairment and is associated with pituitary dysfunction. Past studies have focused on the relationship between ONH, pituitary deficiencies, and brain imaging. However, recent studies have demonstrated the true risk for hypopituitarism lies with the presence or absence of ONH, irrespective of midline brain findings. This study reviewed the relationship between the health of the optic nerve (visual acuity) and pituitary gland (number and age of development of pituitary deficiencies) as a way to stratify risk, regardless of imaging findings. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective chart review of 197 patients seen at a single center from 2013 to 2022. Visual assessment was defined by distance acuity, and the presence of nystagmus or afferent pupillary defect. Pituitary deficiencies were diagnosed per Endocrine Society guidelines. RESULTS: In children with bilateral ONH (bONH), profound visual impairment was associated with more pituitary deficiencies between 0 and 15 years of age. The odds of having any pituitary deficiency were 4.9 times higher (95% confidence interval [95% CI]: 2.4-10.1) for patients with bONH versus unilateral ONH (uONH). Central hypothyroidism was the most common first presenting pituitary deficiency followed by growth hormone across all patients. CONCLUSION: This study shows a significant association between severity of visual impairment and increased probability of pituitary deficiencies in children with bONH versus uONH. Children with ONH require urgent endocrine evaluation due to risk of pituitary deficiencies, but risk stratification may also be based on severity of visual impairment.

Background matching can reduce responsiveness of jumping spiders to stimuli in motion.

Motion and camouflage were previously considered to be mutually exclusive, as sudden movements can be easily detected. Background matching, for instance, is a well-known, effective camouflage strategy where the colour and pattern of a stationary animal match its surrounding background. However, background matching may lose its efficacy when the animal moves, as the boundaries of the animal become more defined against its background. Recent evidence shows otherwise, as camouflaged objects can be less detectable than uncamouflaged objects even while in motion. Here, we explored whether the detectability of computer-generated stimuli varies with the speed of motion, background (matching and unmatching) and size of stimuli in six species of jumping spiders (Araneae: Salticidae). Our results showed that, in general, the responsiveness of all six salticid species tested decreased with increasing stimulus speed regardless of whether the stimuli were conspicuous or camouflaged. Importantly, salticid responses to camouflaged stimuli were significantly lower compared with those to conspicuous stimuli. There were significant differences in motion detectability across species when the stimuli were conspicuous, suggesting differences in visual acuity in closely related species of jumping spiders. Furthermore, small stimuli elicited significantly lower responses than large stimuli across species and speeds. Our results thus suggest that background matching is effective even when stimuli are in motion, reducing the detectability of moving stimuli.

Spatial resolution and optical sensitivity in the compound eyes of two common European wasps, Vespula germanica and Vespula vulgaris.

Vespula germanica and Vespula vulgaris are two common European wasps that have ecological and economic importance as a result of their artificial introduction into many different countries and environments. Their success has undoubtedly been aided by their capacity for visually guided hunting, foraging, learning and using visual cues in the context of homing and navigation. However, the visual systems of V. germanica and V. vulgaris have not received any deep attention. We used electrophysiology, together with optical and anatomical techniques, to measure the spatial resolution and optical sensitivity of the compound eyes of both species. We found that both wasps have high anatomical spatial resolution with narrow interommatidial angles (Δϕ between 1.0 and 1.5 deg) and a distinct acute zone in the fronto-ventral part of the eye. These narrow interommatidial angles are matched to photoreceptors having narrow angular sensitivities (acute zone acceptance angles Δρ below 1.3 deg), indicating eyes of high spatial resolution that are well suited to their ecological needs. Additionally, we found that both species possess an optical sensitivity that is typical of other day-flying hymenopterans.

Visual deterioration outcomes following optic pathway glioma treatment: a 12-year single institution retrospective study.

OBJECTIVE: The surgical treatment of optic pathway gliomas (OPG) remains controversial, with visual outcomes often unpredictable. The present study explored surgical and clinical factors influencing visual acuity (VA) after OPG treatment and developed anatomical subtypes correlated with clinical symptoms. METHODS: Children with OPG who underwent initial partial tumor resection at Beijing Tiantan Hospital from January 2011 to December 2022 were retrospectively analyzed. Multivariate logistic regression and random forest analyses were performed to identify risk factors for post-treatment VA deterioration and a decision tree model was created based on significant factors. RESULTS: A total of 140 patients were enrolled. Multivariate logistic regression analysis identified surgical approach and initial VA as independent predictors of post-treatment VA deterioration (P < 0.05). Surgical approach, initial VA, and extent of tumor resection were the most significant factors for risk assessment and were included in the decision tree model, with surgical approach as the most important "root" node. The model demonstrated good predictive performance, with area under the curve values of 0.75 and 0.66 for the training and test datasets, respectively. A simple anatomical classification was developed, which revealed clinical characteristic differences among OPG types. Meanwhile, a correlation analysis of post-treatment visual deterioration was performed for each of the three anatomical types. CONCLUSION: This study offers a predictive model for visual outcomes following initial tumor-reduction surgery in OPG patients, which may help in visual outcomes risk stratification. Additionally, the anatomical classification effectively indicates OPG growth direction, offering potential insights into clinical symptoms.

Eye morphology contributes to the ecology and evolution of the aquatic avifauna.

Aquatic birds are notable among the global avifauna for living in environments exposed to large amounts of light. Despite growing evidence that visual adaptations to light underly the ecology and evolution of the avian tree of life, no comprehensive comparative analysis of visual acuity as approximated by eyes size exists for the global aquatic avifauna. Here, I use Stanley Ritland's unpublished dataset of measurements for axial length collected from museum specimens to explore the ecology and evolution of eye size variation for half of the aquatic avifauna (N = 464 species). After correcting for body mass allometry and incorporating phylogenetic relationships, aquatic species had significantly smaller eyes compared to terrestrial species. Furthermore, species using hyperopic foraging manoeuvres, exhibiting carnivorous and insectivorous diets, and displaying nocturnal behaviour had larger eyes. Plunge-divers (e.g. boobies and tropic birds) and stalkers (e.g. herons) had the largest relative eye sizes, especially species identifying prey at higher altitudes or longer distances. Underwater pursuit-divers foraging at greater depths had larger eyes, likely due to the dramatic attenuation of light in the deep ocean. Overall, residual eye size was phylogenetically conserved (l = 0.94), with phylogeny alone explaining 62% of residual eye size variation. Collectively, these results suggest that the relatively bright environments found in aquatic ecosystems negate the adaptive benefits of costly metabolic investments associated with developing and maintaining larger eyes, while also reducing the potential occurrence of disability glare. Strong correlations between eye size and foraging ecology in different aquatic environments corroborate similar comparative studies of terrestrial birds and underscore the central role that vision has played in driving the ecology and evolution of the global avifauna.

Improved visual outcomes of central retinal artery occlusion with local intra-arterial fibrinolysis beyond the conventional time window.

Local intra-arterial fibrinolysis (LIF) is a promising therapeutic option for CRAO. However, the narrow time window of 6 h has greatly limited the application of LIF. In this study, we explored the efficacy of LIF beyond the conventional time windows and compared the result with conservative therapy. This prospective study included 179 CRAO patients with baseline visual acuity (VA) ≤ 20/400 treated at Renmin Hospital of Wuhan University. The mean time from vision loss to presentation was 5.5 days. 58 patients received conventional standard therapy (CST) alone.121 patients underwent LIF. Main outcome was VA improvement ≥ 0.3 logMAR. Secondary outcome was a favorable VA outcome of 20/200 or better. Logistic regressions were performed to identify predictors of visual improvement. 43% patients in the LIF group experienced VA improvement versus 19% with CST (P = 0.002). LIF was associated with 4.0-fold higher likelihood of visual improvement compared to CST (P = 0.001). Poor baseline VA (light perception or no light perception) and shortened prothrombin time (PT) were associated with greater chance of visual improvement with LIF. However, LIF showed no significant advantage over CST for favorable VA outcomes. No major complications occurred. LIF beyond the therapeutic time window improved vision in functionally blind CRAO patients and showed better efficacy when compared with CST. PT may be a potential predictor of visual outcome after LIF. Our findings could complement existing time-based treatment guidelines and potentially allow for personalized decisions on the use of LIF beyond time windows.

Effect of spectacle correction on hyperopic children.

Background: Hyperopia is a significant refractive error in children, often leading to vision impairment. This study aimed to investigate whether partial or full spectacle correction is benefit for hyperopia in preschool-aged children. Methods: A retrospective study was conducted on hyperopic children visited to teaching medical center outpatient clinic between October 2011 and October 2018, and were categorized into three groups: full correction, overcorrection, and undercorrection. The study was approved by the institutional ethical committee of Tri-Service General Hospital. Results: Following a minimum of one-year follow-up period, no statistically significant differences were observed in best-corrected visual acuity (BCVA) among children receiving full, over, or under spectacle correction. Notably, the overcorrection group exhibited a significant reduction in spherical equivalent (SE) compared to both the full and under correction groups, indicating a better SE with spectacle overcorrection. Conclusions: Spectacle overcorrection may offer potential benefits for enhancing SE in preschool children with hyperopia. Nevertheless, further investigation through randomized controlled trials is warranted to establish the validity of this approach and its impact on visual outcomes in this hyperopic pediatric population.

Evaluation of the Amblyopia tracker app.

PURPOSE: The Amblyopia tracker app has been developed to be a tool for parents to monitor changes in vision at home during amblyopia treatment. The aims of this study were to evaluate the feasibility and repeatability of parents testing their children at home and to compare home test results to an assessment in clinic by an orthoptist. METHODS: Children (age < 18 years) with amblyopia (interocular acuity difference of ≥ 0.2logMAR) were recruited. Parents were asked to test their child with the app three times during a two week period followed by an online questionnaire about the usability. Participants also tested within 48 h of their appointment where the measurement was repeated by an orthoptist. RESULTS: Out of 277 potential participants contacted, 37 completed three home measurements, mean age 6.8 years (SD 2.94). Home tests comparisons were made between test two and three to ensure familiarity with the process. Paired t-tests showed no statistically significant difference for either eye or the interocular acuity difference (IAD). However, 29% had a difference in IAD of more than 0.1logMAR on repeated testing, with a maximum of 0.4logMAR difference in the IAD. Questionnaire responses from the parents who participated were predominantly positive with 97% of respondents saying they would use it if were available. Comparison of home and clinical measurements (n = 23, mean age 6.72 SD 2.60) showed no statistically significant differences for either eye or interocular acuity difference (paired t-test, p > 0.3 in all cases). CONCLUSION: Results show no statistically significant differences for the Amblyopia tracker app when used by parents at home on repeated testing, or between the home test by a parent and the test by a clinician. However, variability in the results does indicate that further improvements are required to ensure the results can be used as a reliable clinical tool.

Effect of different screen brightness and devices on online visual acuity test.

PURPOSE: This study aimed to study the difference in test results of online visual acuity (VA) test under different devices and screen brightness conditions and to compare online VA test with Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: Healthy volunteers with the best corrected VA of 0.0 LogMAR or higher were recruited. VAs under ETDRS were tested first, and then online VA test (the Stanford Acuity Test, StAT) visual acuities using iPad Air2 and Microsoft Surface pro4 under 50% and 100% screen brightness were performed. The VA results and the testing times were compared between different devices and screen brightness conditions. RESULTS: A total of 101 eyes were included in this study. The VA results measured by the StAT were better than those of ETDRS. The VA results measured at 100% screen brightness were better than those of 50% brightness (mean difference, 0.013 logMAR at most, less than 1 letter); the VA results measured by iPad Air2 were better than those of Surface pro4 (mean difference, -0.009 logMAR at most, less than 1 letter). Significantly less time was spent on VA testing under StAT than that under ETDRS. CONCLUSION: The impact of screen brightness and the device on the VA results generated by online VA tests was clinically insignificant. In addition, online VA tests are found to be reliable and more time efficient than ETDRS.

Effects of grating stimulation on vision in individuals with amblyopia: a systematic review and meta-analysis.

PURPOSE: To investigate the effects of Cambridge Stimulator with grating element stimulation on visual acuity (VA), grating acuity (GA), and contrast sensitivity (CS) in patients with amblyopia. METHODS: Three electronic databases (PubMed, Embase, and Cochrane Library) were searched for studies published from January 1970 to November 2022. The searched studies were reviewed and extracted independently by two authors. The included studies were evaluated by the Cochrane risk of bias. A meta-analysis calculating Hedges' g effect-size metric with 95% confidence intervals using random-effects DerSimonian-Laird model was employed. Heterogeneity was estimated using I2 statistics. Outcomes of interest included VA, GA, and CS. RESULTS: A total of 1221 studies were identified. Twenty-four studies including 900 subjects met the inclusion criteria. The outcome measure of all visual indexes (VA: Hedges' g of - 0.43, 95% CI = - 0.81 to - 0.05, I2 = 86%, p = 0.02; GA: Hedges' g of 3.79, 95% CI = 1.05 to 6.54, I2 = 98%, p = 0.01; CS: Hedges' g of 0.64, 95% CI = 0.19 to 1.09, I2 = 41%, p = 0.00) significantly favored in the grating group. CONCLUSIONS: Grating stimulation may be a positive help for visual functions in patients with amblyopia. The effects of grating stimulation on VA and CS appear to be opposite. This study is registered with www.crd.york.ac.uk/prospero/ (CRD42022366259).

Treadmill-walking impairs visual function in early glaucoma and elderly controls.

AIMS: Impaired vision is an additional risk factor in elderly for falls. We investigated the hypothesis that treadmill (TM) walking affects visual function in both healthy elderly and those with early-moderate visual dysfunction due to glaucoma. METHODS: Thirty healthy controls (HC) aged 64-83 years and 18 glaucoma patients (GLA) aged 62-82 years participated in this cross-sectional study. The impact of TM-walking on visual function was assessed binocularly for (i) best-corrected visual acuity (BCVA) with and without crowding effect, (ii) contrast sensitivity (CS), and (iii) and visual field (mean deviation, VF-MD). Visual function was tested while participants were standing or during TM-walking for 2 speed conditions: (i) fast walking at their preferred speed and (ii) walking at a fixed speed of 3.5 km/h. RESULTS: GLA, most with early-moderate VF loss, performed equally well as HC. Independent of GROUP, an impact of SPEED on visual functions was statistically evident with large statistical effect size for (i) both types of BCVA with a mean loss of 0.02-0.05 logMAR (η2 = 0.41) and (ii) VF-MD with mean loss of 1 dB (η2 = 0.70), but not for CS. CONCLUSIONS: Here, we introduce a paradigm for the assessment of visual function during walking. We provide proof-of-concept that our approach allows for the identification of walking induced visual function loss, i.e., a deterioration of BCVA and VF-sensitivity during TM-walking in both groups. It is therefore of promise for the investigation of the relation of vision impairment and mobility, ultimately the increased frequency of falls in advanced glaucoma.

Choroidal hypertransmission width on optical coherence tomography: a prognostic biomarker in idiopathic macular hole surgery.

PURPOSE: To test the hypothesis that optical coherence tomography (OCT) choroidal hypertransmission width (CHW) is a prognostic biomarker in idiopathic macular hole (MH) surgery METHODS: Retrospective cohort study of consecutive patients undergoing successful pars plana vitrectomy for idiopathic MH. We collected demographic, clinical, and OCT variables at the preoperative and last available visits. Two investigators assessed the following OCT parameters: MH minimum diameter, base diameter, CHW, ellipsoid zone, and external limiting membrane status (absent vs. present). Delta CHW was calculated as the difference between CHW and MH minimum diameter. Linear models were used to investigate factors associated with postoperative best-corrected visual acuity (BCVA) and BCVA change. RESULTS: Thirty-six eyes (36 patients) with a median (interquartile range (IQR)) follow-up of 9 (8-11) months were included. The median BCVA (IQR) improved from 0.75 (1-0.6) logMAR preoperatively to 0.2 (0.6-0.1) logMAR at the last visit (p < 0.001). Preoperative MH minimum diameter (for a 10-µm increase, estimate (standard error (SE)): 0.009 (0.003) logMAR, p = 0.003), base diameter (for a 10-µm increase, 0.003 (0.001) logMAR, p = 0.032), CHW (for a 10-µm increase, 0.008 (0.002) logMAR, p < 0.001), and delta CHW (for a 10-µm increase, 0.013 (0.005) logMAR, p = 0.009) were significantly associated with postoperative BCVA. The proportion of variance explained was the highest for MH CHW (R2 0.35), followed by minimum MH diameter (R2 0.24), delta CHW (R2 0.19), and MH base diameter (R2 0.14). None of the study variables was associated with delta BCVA. CONCLUSION: Preoperative CHW is associated with postoperative visual acuity in patients undergoing successful idiopathic MH surgery and may be a useful OCT prognostic biomarker.

Anti-VEGF therapy for the long-term management of diabetic macular edema: a treat-to-target strategy based on macular morphology.

In an aging population, the prevalence and burden of diabetes mellitus, diabetic retinopathy, and vision-threatening diabetic macular edema (DME) are only expected to rise around the world. Similarly to other complications of diabetes mellitus, DME requires long-term management. This article aims to review the current challenges associated with the long-term management of DME, opportunities to improve outcomes for patients, and to develop a treat-to-target strategy based on macular morphology. At present, intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for the management of DME; however, best-achievable vision outcomes with treatment are reliant on frequent injections and close monitoring, which are difficult to maintain in current clinical practice because of the burden this imposes on patients. Achieving and maintaining good vision with treatment are the most important factors for patients with DME. Landmark trials have shown that vision gains with anti-VEGF therapy are typically accompanied by anatomical improvements (e.g., reductions in retinal thickness); therefore, multimodal imaging measures of macular morphology are often used in patients with DME to guide real-world treatment decisions. We would like to propose a hypothetical treat-to-target algorithm to guide physicians on treatment strategies for the long-term management of DME. Alternative measures of retinal fluid (e.g., persistence, stability, location) may be stronger predictors of visual acuity in DME, although further research is required to confirm whether alternate quantifiable biomarkers such as subretinal fluid and intraretinal fluid volumes can be used as a biomarker of clinical improvement. Identifying novel biomarkers and treatments that target neuroinflammation and neurodegeneration, improving patient-physician communication around treatment adherence, and using treat-to-target measures may help to ensure that the long-term benefits of treatment are realized.

Real-world experience of using stereotactic radiotherapy combined with anti-vascular endothelial growth factor to treat neovascular AMD.

INTRODUCTION: Adjunctive treatment or longer-acting drugs are required to treat nAMD to help ease burdens for patients and hospital clinics alike. Stereotactic therapy is one such option, providing a reduction in the number of injections over time. OBJECTIVE: To determine the clinical outcomes in a cohort of patients with nAMD receiving a combination therapy of stereotactic radiotherapy (SRT) with intravitreal anti-VEGF injections (IVI). METHOD: A retrospective analysis of 74 patients with nAMD, who had received IVI and SRT (16 Gray maximum dose to the macula) at a large tertiary university eye hospital, between March 2018 and September 2019 was performed. The number of IVIs, visual acuity (VA), and central retinal thickness (CRT) were evaluated at 12, 24, and 36 months after patients received SRT and compared to the same time interval prior to SRT. RESULTS: Follow-up data at 12, 24, and 36 months following and prior to SRT was available for 74, 48, and 22 patients respectively. Overall there was a significant reduction in the number of injections post-SRT. Twelve months following SRT, the median number of IVI was reduced by 1 (p < 0.05). The reduction in the median number of IVI was significantly reduced by 3 and 6 injections at 24- and 36-month follow-up respectively (p < 0.05). The CRT was significantly reduced post-SRT compared to the baseline values at all time periods. There was no statistically significant difference in VA at 12-month follow-up compared to baseline. The VA, however, significantly decreased at 24- and 36-month follow-up (p < 0.05). CONCLUSION: A therapy combining SRT with IVI has shown an overall reduction in the number of injections required in nAMD patients at 12, 24, and 36 months following SRT compared to IVI treatment alone. These real-world outcomes are comparable to other studies while also confirming the maintenance of the reduced frequency of required IVI for patients with nAMD.