Vision impairment has profound consequences for everyday functioning and quality of life. This review summarises recent evidence on the impact of vision impairment in three functional domains: mobility and falls risk, driving, and the interaction between vision impairment and hearing. Individuals with vision impairment often adopt more cautious gait and visual search behaviours; however, they remain less stable and at increased falls risk, dependent on the type and severity of vision impairment. Wearable technologies enable continuous measurement of movement in naturalistic settings. Future research should leverage these tools to examine daily mobility patterns, fatigue and environmental exposure, and evaluate interventions in real-world contexts. Both central and peripheral vision play critical roles in driving. However, the impact of vision impairment on driving outcomes depends on the severity of loss as well as drivers' insight into their vision impairment and adoption of behavioural and compensatory strategies. Future studies should incorporate naturalistic driving methods and advanced vehicle technologies to explore compensatory behaviours and interventions and their impact on real-world safety. Hearing abilities may improve or decline following vision loss, depending on the task. Musical perception and pitch discrimination are often enhanced in early-onset blindness, possibly reflecting recruitment of visual cortical areas by auditory processing, while performance on complex spatial hearing tasks can be poorer, as vision calibrates auditory spatial representations. Future research should determine how cross-modal plasticity impacts performance and explore how auditory training or multisensory rehabilitation may enhance functional adaptation. In summary, research highlights the importance of both central and peripheral vision and behavioural adaptations and compensatory strategies, with key challenges being the ability to measure real-world function and understand individual variability. Future work should integrate advanced assessment technologies and interdisciplinary approaches to better characterise functional outcomes and inform interventions to enable functional independence.
Age-related macular degeneration is a chronic and progressive disease that typically develops after the age of 50. Characterized by visual distortions, image blurring, and gradual central vision loss, age-related macular degeneration significantly impairs patients' ability to perform everyday activities and contributes to a marked reduction in quality of life. The gold standard treatment for the neovascular form of this condition consists of intravitreal injections. This therapy offers patients the possibility of improved vision-related quality of life by slowing disease progression and partially restoring visual function to levels approximating those prior to the onset of the condition. The aim of this study was to examine vision-related quality of life in individuals with neovascular age-related macular degeneration prior to treatment and following a course of seven intravitreal injections. The study also aimed to analyze its association with visual acuity, contrast sensitivity, and the occurrence and severity of metamorphopsia and central scotoma. This survey-based study was carried out using the author's questionnaire and a standardized research tool-the Polish version of National Eye Institute Visual Functioning Questionnaire. It also involved the analysis of the patients' medical records. The study group consisted of 121 patients (121 eyes), comprising 60 women and 61 men, aged between 51 and 90 years. Following a course of intravitreal injections, a statistically significant improvement in vision-related quality of life, as measured by the Visual Functioning Questionnaire, was observed. The analysis also demonstrated an association between quality of life and visual function parameters. Vision-related quality of life in patients with neovascular age-related macular degeneration was low at baseline and showed a modest improvement following initiation of intravitreal anti-VEGF therapy over the follow-up period. Across time points, better visual acuity, higher contrast sensitivity, and fewer visual disturbances on the Amsler grid were associated with higher vision-related quality of life scores. This study highlights the potential psychosocial benefits of intravitreal therapy in nAMD and may help support patients in initiating treatment or in maintaining adherence to continuing therapy.
To determine the prevalence and causes of reduced vision in childhood. Cross-sectional analysis included five cohorts aged; 3-5 years old (n = 986) from the Sydney Paediatric Eye Disease Study (SPEDS), 6 years (n = 1739) and 12 years (n = 2345) from the Sydney Myopia Study (SMS) and the 5 year follow-up of SMS at 12 years (n = 1111) and 17 years (n = 1649) in the Sydney Adolescent and Vascular Eye disease Study (SAVES). All children had a comprehensive ocular examination, including visual acuity (VA) with and without refractive correction. Reduced uncorrected VA was defined as worse than 6/12 (logMAR 0.30). A longitudinal analysis was also conducted to identify incident cases of reduced vision between SMS baseline and SAVES follow-up among children assessed at both time points. The overall prevalence of reduced vision based on unaided visual acuity increased with age from 4.5% in SPEDS 3-5 year olds to 17.7% in SAVES 17 year olds (p < 0.001). The proportion of reduced vision caused by refractive error, amblyopia, strabismus and pathology also varied between cohorts. In the younger cohorts, amblyopia accounted for 21% of SPEDS 3-5 year olds and 28% of SMS 6 year olds with reduced vision. There was a substantial decline in the proportion of reduced vision attributed to amblyopia in the older cohorts, while refractive error increased. Myopia contributed to 18% of children with reduced vision in SPEDS 3-5 years and SMS 6-year-olds and increased to over 80% in SMS 12-year-olds, SAVES 12-year-olds and 17-year-olds. Targeted preschool screening for amblyopia is supported as it occupied a higher proportion of the younger ages. Community education to promote wearing glasses in adolescence for those with myopia is warranted.
To identify key recent research in the field of binocular vision anomalies, highlight important advances and identify where new developments are emerging. This allows identification of gaps in our knowledge, which may inform future research efforts. A narrative review of the peer-reviewed literature on amblyopia, strabismus and non-strabismic binocular vision anomalies (NSBVA) was carried out under the following headings: prevalence, impact and new developments (e.g., in technology, treatment and disease understanding). The prevalence of amblyopia and strabismus continues to be studied intensively in different geographical regions and amongst different ethnicities, with results revealing large variations in rates of esotropia versus exotropia. Studies of NSBVA prevalence frequently suffer from major methodological limitations, leaving uncertainty about their prevalence and impact. This stems from variability in diagnostic criteria and an uncertain link between the conditions and the symptoms generated. There has been an upsurge in evaluations of the impact of strabismus and amblyopia. Along with their effect on vision, changes are seen in visuomotor and other functional task performance (e.g., reading). Additionally, there are important psychosocial impacts (e.g., in self-confidence), particularly when strabismus is present. Digital applications are emerging for both detecting and treating binocular anomalies, although much remains to be done to establish their acceptability to patients and overall usefulness. The quality of the research evidence guiding amblyopia treatment is much stronger than for strabismus, where evidence for the treatment of the condition is still lacking. With greater awareness of the need for robust research evidence, the knowledge gaps concerning binocular vision anomalies are becoming clearer. As high-quality research evidence emerges and armed with a greater understanding of their prevalence and impact, it is hoped that future management of these visual anomalies will be based more upon robust research evidence and less upon clinical consensus.
This is a summary of the original article "Four-Year Outcomes of Faricimab in Diabetic Macular Edema: Results From the RHONE-X Extension Trial." RHONE-X was a phase 3, multicenter, nonrandomized, 2-year open-label extension of the YOSEMITE/RHINE clinical trials. RHONE-X assessed the long-term safety (primary endpoint) and efficacy (exploratory) of faricimab using a treat-and-extend (T&E) protocol in patients with diabetic macular edema (DME). Patients in YOSEMITE/RHINE who received faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg T&E, or aflibercept 2.0 mg Q8W received faricimab 6.0 mg up to Q16W T&E (based on prespecified vision and anatomic criteria) for a further 2 years in RHONE-X. Faricimab was well tolerated through 2 years of RHONE-X, and adverse events reported were consistent with the known safety profile of faricimab. Vision and anatomical improvements achieved during YOSEMITE/RHINE were maintained through RHONE-X. In patients treated with aflibercept during YOSEMITE/RHINE, the proportion achieving absence of DME (CST < 325 µm) increased after switching to faricimab. Approximately 80% of patients were on a faricimab dosing interval of ≥ Q12W at the end of 4 years. These findings demonstrated the long-term safety, efficacy, and durability of faricimab T&E in patients with DME.
To develop a consensus-based classification system and questionnaire for the standardized assessment and reporting of dysphotopsias following ophthalmic procedures. Systematic review and Delphi consensus process. Twenty ophthalmic specialists with expertise in glaucoma, cataract/refractive surgery, and cornea participated in this Delphi consensus survey. A systematic literature search was conducted using Ovid MEDLINE and Embase to identify randomized controlled trials and observational studies reporting on dysphotopsias. Reported symptoms, assessment questionnaires, and individual question items were extracted to create a comprehensive list of potential classification items. These items were refined through iterative Delphi consensus surveys involving ophthalmic specialists, who evaluated each item for inclusion, exclusion, or rewording, and could propose the addition of new items. Consensus was defined a priori as ≥80% agreement among panelists. This iterative process allowed for progressive refinement of the classification system and continued until at least 80% of all proposed items achieved consensus. The proportion of ophthalmic specialists who chose to include or exclude specific dysphotopsia symptoms, and additional items of the questionnaire including baseline characteristics, environmental modifiers, quality of life, and attempted management strategies. Following the screening of 5,059 articles, 142 studies met inclusion criteria, identifying 34 unique dysphotopsia symptoms and 76 individual questionnaire items. Participants reached consensus on 53 of 63 items (84.1%) over two rounds of Delphi surveys. Items that did not meet inclusion or exclusion thresholds after the second round were excluded from the final classification system. The finalized classification system included 11 baseline clinical variables, 7 positive dysphotopsia symptoms (halos, glare/dazzle, starbursts, arcs, lines/streaks, ghosting, and flickering/shimmering), 1 negative dysphotopsia symptom (peripheral crescent/shadow), 5 environmental modifiers, 2 quality-of-life and mental health items, and 8 attempted interventions. These elements were consolidated into the DYsphotopsia Symptom Questionnaire and Outcomes (DYSQO) intended for clinical and research applications. A standardized classification system for the reporting of dysphotopsias following ophthalmic procedures was developed using the Delphi consensus process. The adoption of this tool in research and clinical practice may enhance the consistency, clarity, and quality of dysphotopsia reporting, enabling comparisons across interventions and enhancing evidence-based patient care.
To identify predictors of retinal detachment (RD) and final visual outcome in acute retinal necrosis (ARN). This retrospective cohort study included ARN patients who were treated at a tertiary center between 2009 and 2022. The incidence and risk factors of RD and predictors of final vision loss (< 20/200) were analyzed. 156 ARN patients (58.3% male, mean age: 47.74 ± 15.49 years) were included in our study. RD occurred in 51 eyes (32.7%), at a median of 8.0 weeks from ARN onset. Extensive retinitis (four vs. one quadrant involvement) independently predicted RD (adjusted OR 3.45, p = 0.042). Poor final visual outcome (< 20/200) occurred in 79% of eyes. Worse baseline visual acuity was the strongest predictor of poor final vision (adjusted OR 5.58, p = 0.003). In contrast, presence of retinal hemorrhages at presentation (adjusted OR 0.185, p = 0.011) were associated with better final visual outcomes. In ARN, severe initial disease, characterized by panretinal necrosis and poor presenting acuity, predisposes to RD and profound vision loss. Most detachments occur within two months of onset, highlighting the need for vigilant early monitoring. Baseline visual acuity is a powerful prognostic indicator, whereas adjunctive treatments (prophylactic laser, intravitreal antivirals) did not independently improve outcomes. To our knowledge, this is the largest cohort of ARN patients reported from the Middle East and one of the few studies globally to incorporate time-to-event analysis and ROC-based visual prognostication. These findings provide region-specific data that refine global risk models for ARN. These findings can guide risk stratification and management decisions in ARN.
The Spanish Low Vision Quality of Life Questionnaire (SLVQOL) assesses vision-related quality of life effectively but requires significant administration time. This study aimed to develop and validate a psychometrically robust short-form version (SF-SLVQOL) using Rasch analysis to reduce respondent burden while maintaining measurement precision in Spanish-speaking populations with visual impairment. Data from the original SLVQOL validation study (n = 365; 170 visually impaired, 195 controls) were reanalysed using Partial Credit Model analysis in WINSTEPS. Items were systematically reduced through iterative removal based on point-biserial correlations (< 0.4) and misfit statistics (infit/outfit outside 0.7-1.3). The resulting SF-SLVQOL was evaluated for structural validity (unidimensionality, local independence, monotonicity), internal consistency (Cronbach's alpha), criterion validity (correlation with original SLVQOL), construct validity (convergent validity with NEI VFQ-25, known-groups validity across ICD-11 visual impairment categories), differential item functioning by gender and test-retest reliability. The 6-item SF-SLVQOL demonstrated excellent unidimensionality (essential unidimensionality = 93.6%, variance explained = 79.3%), optimal internal consistency (α = 1.00) and high criterion validity (r = 0.95 with original SLVQOL). Convergent validity with the NEI VFQ-25 was confirmed (r = 0.69). The known-groups analysis showed significant discrimination between visual impairment levels (H = 132.67, p < 0.001). Person reliability (0.91) indicated the ability to distinguish 4.3 performance levels. Test-retest reliability was acceptable (ICC = 0.753; 95% CI: 0.569-0.864) with a repeatability limit of 4.89 points. The SF-SLVQOL successfully reduces administration time by 76% while maintaining robust psychometric properties, offering clinicians and researchers an efficient tool for assessing vision-related quality of life in Spanish-speaking populations.
Rare ocular surface inflammatory disorders (OSIDs), such as ocular cicatricial pemphigoid (OCP; 1.3-2/million), Stevens-Johnson Syndrome (SJS; 1-5/million), and ocular graft versus host disease (oGVHD; occurring in >50% of chronic GVHD cases) share overlapping clinical phenotypes. Their defining features include conjunctival cicatrization and chronic inflammation. An incomplete understanding of the underlying immunopathogenesis of these conditions has hindered the development of targeted therapies, leaving patients at risk of permanent vision loss and highlighting the need to define distinct ocular immune profiles. Existing literature indicates elevated levels of neutrophils and macrophages/monocytes, along with major increases in their related secretory factors, IL-8 (P < 0.05) and TNF-α (P < 0.05), at the ocular surface across all three groups. Whereas both B cells and cytotoxic T cells are elevated in oGVHD, OCP is characterized by elevated B cells and a concomitant reduction in cytotoxic T cells. Apart from neutrophils and macrophages/monocytes, the local immune landscape-especially in SJS-has been underexplored. At the molecular level, extensive studies of tears have reported elevated levels of IL-17, CXCR1 (P < 0.01), CTGF (P < 0.05) in OCP; IFN-α and IFN-γ (P < 0.05) in oGVHD; and MCP-1, MIP-1β (P < 0.05) in SJS. These studies also indicate that sampling methods and patients' medication status may influence immune profile outcomes. Comprehensive immunophenotyping studies, coupled with the establishment of pathological links to respective molecular profiles, could advance understanding of condition-specific disease biology.
To assess the effects of stereotactic radiotherapy (SRT) for neovascular age related macular degeneration (AMD) beyond the two year primary outcome of the StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR) trial. Randomised, double masked, sham controlled, device trial involving preplanned recall from standard care. 30 NHS hospitals in the UK. 411 participants aged at least 50 years with chronic, pretreated, active AMD. Participants received one-off 16 Gray SRT or sham SRT delivered using a robotically controlled device. After two years of monthly study visits, participants reverted to routine care, with anti-VEGF drug selection and dosing intervals based on local practice, but with masking maintained, and repeat data collection at years 3 and 4 study visits. The main efficacy outcome at year 4 was the number of anti-VEGF injections, tested for superiority (fewer injections). The other main outcome was visual acuity, tested for non-inferiority (five letter margin). Safety outcomes included adverse events, serious adverse events, and microvascular abnormalities. The same analyses were undertaken at years 2, 3, and 4. A within trial costing analysis was undertaken for participants with four years' follow-up. Of 411 participants (204 (58%) women), 274 were allocated to SRT and 137 to sham SRT. The year 4 intention-to-treat efficacy analysis included 222 (81%) participants in the SRT group and 106 (77%) in the sham SRT group. The SRT group received a mean of 19.1 (standard deviation 10.9) injections over four years versus 21.6 (11.3) with sham SRT, an adjusted decrease of 3.2 injections (95% confidence interval (CI) of difference -5.7 to -0.7). During years 3 and 4, the SRT group received a mean cumulative 8.4 injections versus 8.3 injections in the sham SRT group. The final change in visual acuity in the SRT group was 8.3 letters worse than in the sham group (95% CI of difference -12.7 to -4.0). Adverse event rates were similar between groups, but reading centre-detected microvascular abnormalities occurred in 126/218 SRT treated eyes (58%) and 16/102 (16%) sham SRT treated eyes. Although the overall reduction in intravitreal therapy was maintained to year 4, the inferior vision in SRT treated eyes effectively reversed the conclusions of the year 2 primary outcome analysis and no longer supports the use of SRT to treat neovascular AMD. Including standard care, masked, extended follow-up within a clinical trial may provide useful clinical insight. ClinicalTrials.gov NCT02243878.
Posterior segment eye diseases pose a significant threat to vision-related quality of life, affecting functional independence, psychological health, and social well-being. Conditions such as diabetic retinopathy and age-related macular degeneration are leading causes of blindness, often resulting in severe emotional distress and reduced mobility. Optic neuritis and optic neuropathy can lead to vision loss and increase the risk of depression, particularly in patients with multiple sclerosis. Retinal disorders like central serous chorioretinopathy and retinitis pigmentosa disrupt daily tasks such as reading and driving, thus leading to social isolation and economic burden. Hypertensive retinopathy and retinal detachment further contribute to vision impairment, with long-term implications for functional ability and mental health. Inherited retinal diseases such as Stargardt disease and Leber congenital amaurosis significantly reduce quality of life from an early age and negatively affect education, employment opportunities, and psychological well-being. Additionally, the economic impact of these diseases is substantial, with high treatment costs and productivity loss. On the other hand, vision rehabilitation, psychological support, and advancements in gene and pharmacological therapy can largely mitigate the adverse effects on quality of life associated with posterior segment diseases. Therefore, a comprehensive approach that integrates medical, psychological, and social interventions is essential for improving patient outcomes. Future research should focus on developing innovative treatments and patient-centered care strategies to improve the quality of life for individuals affected by this condition.
The eye is a recognized source of biomarkers for cardiovascular and neurodegenerative disease risk. Here we characterize the breadth of these associations and identify biological axes that may mediate them. Using UK Biobank data, we developed a multi-omic analysis pipeline integrating physiological, radiomic, metabolomic and genomic information. We trained retinal adversarial autoencoders to represent optical coherence tomography images and color fundus photographs as 256-dimensional embeddings. Retinal adversarial autoencoder-derived embeddings were associated with a range of cardiovascular and neurodegenerative diseases, including ischemic heart disease, cerebrovascular disease, Parkinson's disease and dementia. Examining associations across diverse omics datasets, we provide evidence linking ophthalmic imaging features to neurological and cardiovascular anatomy and function, lipid metabolism and gene sets associated with neurodegenerative pathology. Collectively, our findings show that ophthalmic features reflect complex, multisystem biological processes and reinforce the role of the eye as a composite indicator of systemic health.
We assessed the risk of major vision-impairing eye diseases among smokers who quit combustible cigarettes (CC) and switch to non-combustible nicotine or tobacco products (NNTPs) compared with those who completely quit using tobacco. Retrospective cohort study. 179,273 adults from the Korean National Health Insurance Service who smoked CC in 2011-2012 and reported cessation in 2018-2019, classified into complete quitters and NNTP switchers. This nationwide longitudinal cohort study followed participants for up to 6 years and identified incident major vision-impairing eye diseases (cataract, glaucoma, age-related macular degeneration, diabetic retinopathy, and refractive and accommodation disorders) using standardized diagnostic codes. Propensity score matching was applied to emulate a pseudo-randomized comparison, balanced on key demographic, clinical, comorbidity, and lifestyle characteristics. Subdistribution hazard ratios (SHRs) were evaluated using the Fine-Gray subdistribution hazards model accounting for all-cause mortality as a competing risk. Adjusted SHRs for incident major vision-impairing eye diseases. Among 32,316 matched participants followed for a mean of 4.6 years, 6,328 incident major vision-impairing eye disease events occurred. The incidence was 41.1 and 44.0 per 1,000 person-years for complete quitters and NNTP switchers, respectively. Switching to NNTPs was associated with an increased risk of major vision-impairing eye disease (SHR, 1.07; 95% CI, 1.02-1.13). The risk elevation was most pronounced for diabetic retinopathy (SHR, 1.24; 95% CI, 1.00-1.53) and refractive and accommodation disorders (SHR, 1.07; 95% CI, 1.01-1.12). These findings were robust across inverse probability-weighted and Cox proportional hazards models. The association remained consistent in sensitivity analyses and across clinical subgroups. Transitioning from CC to NNTPs is associated with a modest but consistent increase in the risk of major vision-impairing eye diseases compared with complete nicotine abstinence. These findings challenge the assumption that substituting NNTPs for CCs is visually harmless and indicate that, from an ophthalmic perspective, complete cessation of all nicotine products should remain the preferred cessation goal.
To investigate the effect of switching to a different type of myopia control spectacles on myopia progression. This retrospective matched-cohort study involved 1012 children or adolescents who were prescribed myopia control spectacles. Participants were divided into two groups: the change-of-type group (n=253), who switched to a different spectacle type, and the type-maintenance group (n=759), who retained the same type, using 1:3 propensity score matching. The primary outcome was the annual rate of spherical equivalent refraction progression (D/year) compared between and within groups before and after the switch. The initial prescription of myopia control spectacles occurred at a mean age of 9.46±2.11 years. Subsequent prescription (renewing the same type or switching to a new type) was provided at a mean age of 10.63±2.16 years. Before switching spectacles, the change-of-type group exhibited a significantly faster myopia progression rate than the type-maintenance group (-0.66±0.40 D/year vs -0.37±0.49 D/year; p<0.001). After switching, the progression rate slowed in the change-of-type group (mean reduction 0.18 D/year, p<0.001), narrowing the intergroup difference from 0.30 D/year to 0.08 D/year (-0.48±0.61 vs -0.40±0.50 D/year; p<0.001). However, the improved effect in the change-of-type group was not sustained, with myopia progression accelerating again with prolonged use (early vs late phase, -0.33 vs -0.53 D/year, p=0.024). Switching to a different type of myopia control spectacle may help slow myopia progression for children exhibiting suboptimal response to their initial spectacles. However, this beneficial effect tends to wane over time with prolonged wear.
Work-related musculoskeletal disorders (WMSDs) are highly prevalent among healthcare professionals, including optometrists. This study aimed to assess the frequency, severity and contributing factors of WMSDs among Australian optometrists, as well as evaluate their awareness and implementation of ergonomic practices. A cross-sectional online survey was distributed to optometrists in Victoria and South Australia. The survey collected data on demographics, work characteristics, ergonomic awareness, frequency and severity of musculoskeletal discomfort and contributing factors. Quantitative data were analysed using descriptive statistics and correlation analysis. Free-text responses were examined using inductive thematic analysis. Of 119 respondents, 84% reported neck discomfort, 71% shoulder discomfort and 73% lower back discomfort. Pain severity was highest in the neck and shoulders (mean ~6.5/10). Strong Pearson correlations were found between neck, shoulder and upper back discomfort. Repetitive tasks, static postures and awkward positioning were identified as primary contributors to discomfort. Slit lamp-based tasks were most frequently associated with exacerbating pain. Only 20% of respondents were aware of workplace health and safety policies and 97% had not received employer-led training on injury reduction. Thematic analysis revealed significant impacts on professional performance and personal wellbeing. WMSDs are highly prevalent among Australian optometrists, particularly affecting the upper body. There is a lack of ergonomics education and workplace support. These findings highlight the need for improved ergonomics training in optometry education, implementation of workplace health and safety protocols and investment in ergonomic equipment. Future interventions should focus on addressing the identified risk factors and promoting a culture of safety in optometric practice.
We report a rare case of histopathologically confirmed epithelial cell proliferation on the anterior surface of an intraocular lens (IOL) following Descemet stripping automated endothelial keratoplasty (DSAEK). A 61-year-old female with a history of multiple ocular surgeries, including phacoemulsification cataract extraction and DSAEK, was referred for progressive visual deterioration. Clinical examination revealed resistant deposits on the anterior surface of the posterior chamber IOL, confined to the pupillary zone. Despite repeated interventions-including Nd: YAG laser treatment and surgical polishing of the IOL surface-the opacities persisted, ultimately necessitating IOL explantation and histopathological analysis. Light microscopy confirmed epithelial cell proliferation on the IOL surface. Examination of the stained lens revealed a sheath of cellular imprints and ghost cells. Unlike previously reported cases of IOL opacification, von Kossa staining demonstrated no calcium phosphate deposits, suggesting a distinct pathological mechanism originating from epithelial cell proliferation, likely derived from the capsular bag. Epithelial cell proliferation should be considered in the differential diagnosis of unexplained, persistent IOL surface opacities following DSAEK. In this case, definitive diagnosis was established only through histopathological evaluation of the explanted lens.
A2 amacrine cells (AIIACs) are the most important amacrine cells (ACs) in the mammalian retina, as they are the "hubs" for merging rod and cone signals in the inner retina and segregate them into ON and OFF ganglion cell (GC) pathways. It is unclear, however, whether AIIACs send their signals to all types of GCs in the mammalian retina. A major reason for this knowledge gap is that it has not been possible to selectively stimulate AIIACs without stimulating other retinal neurons. In this study, we will use a newly-developed mouse retinal preparation in which channelrhodopsin (a ChR2 [H134R]-Venus fusion protein) is selectively expressed in AIIACs via intravitreal injection of AAV serotype 2 (AAV2) carrying the ACAGW-ChR2-Venus construct (Addgene 20,071). We have identified a titer range within which ChR2 expresses ONLY in AIIACs and not in any other cells, yet large and clear ChR2-elicited postsynaptic signals can be observed. We examined effects of ChR2-elicited AIIAC depolarization on four types of alpha GCs, the ON-sustained αRGC (sONαGC), OFF-sustained αRGC (sOFFαGCs), ON-transient αRGC (tONαGCs) and OFF-transient αRGC (tOFFαGCs), and found that AIIAC depolarization mediates the sONαGC and sOFFαGC responses via the AIIAC-cone DBCR/MC (rod/M-cone ON Bipolar Cell) gap junction pathway and the AIIAC-OFFαGC glycinergic pathway, respectively. AIIAC depolarization did not affect the tONαGCs and tOFFαGCs, whose responses might be mediated by other ACs. These experiments demonstrate that AIIAC depolarization mediates the responses of a subpopulation of ON and OFF GC types, suggesting that signals from any single retinal neuron type participate in restricted, cell-type-specific circuitries linked to retinal output pathways.
Ocular diseases result from a complex interaction of environmental and metabolic factors. The increasingly prevalent sedentary lifestyle and dietary patterns characterized by high sugar and ultra-processed food intake substantially elevate the risk of hyperglycemia. Hyperglycemia induces dysregulation of core metabolic pathways, such as overactivation of the polyol and hexosamine pathways, aberrant activation of protein kinase C, and accumulation of advanced glycation end products. Hyperglycemia further triggers tissue-specific molecular and cellular events in various ocular structures. These mechanisms collectively contribute to ocular damage and drive the progression of sight-threatening ocular diseases, including myopia, glaucoma, diabetic retinopathy, diabetic cataract, and diabetic keratopathy. A comprehensive understanding of these mechanisms provides a critical theoretical foundation for developing precision strategies for the prevention and management of hyperglycemia-associated ocular complications.
A safety and feasibility study was conducted using balloon angioplasty to treat ophthalmic artery (OA) stenoses in patients with age-related macular degeneration (AMD) with geographic atrophy (GA). Patients ≥ 60 years of age received OA angioplasty using an investigational catheter system and were followed for 6 months. Changes in stenosis, best-corrected visual acuity (BCVA), MNRead acuity charts, ophthalmic imaging, and a validated questionnaire were evaluated. Eleven patients were treated. All adverse events were treated as needed and resolved without sequelae. Treated patients demonstrated a mean improvement over baseline in BCVA (P = .01) and reading speed (P = .03) at study exit. Mean subfoveal choroidal thickness increased over baseline (P = .004) and fellow eyes (P = .03) through week 4, remaining above baseline at study exit. Participants reported mean improvements in both mobility and reading. Treating OA stenoses using angioplasty in patients with GA was safe with apparent visual function benefit.
To compare, in the context of a population-scale biobank, associations of established risk factors and severity biomarkers with different glaucoma disease definitions. Observational cohort study. 503,325 participants in UK Biobank. Odds ratios (ORs) for associations of established risk factors (corneal-compensated intraocular pressure [IOPcc], polygenic risk score [PRS]) and clinical biomarkers of disease severity (macular retinal nerve fiber layer [mRNFL], ganglion cell layer [mGCL]) with different glaucoma definitions. Participants without glaucoma (n=481,772) were compared to those with: (1) a diagnosis of glaucoma based on self-report, hospital inpatient, or primary care records ("diagnosis-only"; n=16,154); or (2) a diagnosis plus evidence of treatment with glaucoma-specific medication or surgery ("diagnosed-and-treated"; n=7,012), either at baseline or during follow-up. For participants in the highest 5% of IOPcc compared with the remainder, ORs were 23.6 (95% CI: 21.3-26.2) in the diagnosed-treated group versus 11.4 (10.6-12.3; p<1x10-10 for difference) in the diagnosed-only group. Corresponding ORs were: 8.0 (6.9-9.2) in diagnosed-treated vs 4.7 (4.2-5.3; p=2.32x10-7 for difference) in diagnosed-only for the thinnest 5% mRNFL; 7.1 (6.1-8.3) in diagnosed-treated vs 4.2 (3.7-4.7; p=2.53x10-7 for difference) in diagnosed-only for the thinnest 5% mGCL; and 8.4 (7.9-8.8) in diagnosed-treated vs 5.6 (5.4-5.9; p<1x10-10 for difference) in diagnosed-only for the highest 5% PRS. There were similar patterns for the other risk factors studied. Definitions of glaucoma that combine both diagnostic and treatment evidence yielded substantially stronger odds ratios with IOPcc, mRNFL, and mGCL than definitions based on diagnostic evidence alone, suggesting implications for studies of glaucoma in population biobanks.