Relationship between Psychophysical Measures of Retinal Ganglion Cell Density and In Vivo Measures of Cone Density in Glaucoma.

PURPOSE: Considerable between-individual variation in retinal ganglion cell (RGC) density exists in healthy individuals, making identification of change from normal to glaucoma difficult. In ascertaining local cone-to-RGC density ratios in healthy individuals, we wished to investigate the usefulness of objective cone density estimates as a surrogate of baseline RGC density in glaucoma patients, and thus a more efficient way of identifying early changes. DESIGN: Exploratory cohort study. PARTICIPANTS: Twenty glaucoma patients (60% women) with a median age of 54 years and mean deviation (MD) in the visual field of -5 dB and 20 healthy controls (70% women) with a median age of 57 years and a mean MD of 0 dB were included. METHODS: Glaucoma patients and healthy participants underwent in vivo cone imaging at 4 locations of 8.8° eccentricity with a modified Heidelberg Retina Angiograph HRA2 (scan angle, 3°). Cones were counted using an automated program. Retinal ganglion cell density was estimated at the same test locations from peripheral grating resolution acuity thresholds. MAIN OUTCOME MEASURES: Retinal cone density, estimated RGC density, and cone-to-RGC ratios in glaucoma patients and healthy controls. RESULTS: Median cone-to-RGC density was 3.51:1 (interquartile range [IQR], 2.59:1-6.81:1) in glaucoma patients compared with 2.35:1 (IQR, 1.83:1-2.82:1) in healthy participants. Retinal ganglion cell density was 33% lower in glaucoma patients than in healthy participants; however, cone density was very similar in glaucoma patients (7248 cells/mm2) and healthy controls (7242 cells/mm2). The area under the receiver operator characteristic curve was 0.79 (95% confidence interval [CI], 0.71-0.86) for both RGC density and cone-to-RGC ratio and 0.49 (95% CI, 0.39-0.58) for cone density. CONCLUSIONS: Local measurements of cone density do not differ significantly from normal in glaucoma patients despite large differences in RGC density. There was no statistically significant association between RGC density and cone density in the normal participants, and the range of cone-to-RGC density ratios was relatively large in healthy controls. These findings suggest that estimates of baseline RGC density from cone density are unlikely to be precise and offer little advantage over determination of RGC alone in the identification of early glaucomatous change.

Factors Influencing the Use of Domestic Violence Restraining Orders in Los Angeles.

Domestic violence restraining orders (DVROs), although a widely used legal intervention in preventing future risk of intimate partner violence (IPV), there is a lack of documentation on the facilitators and barriers of utilization of DVROs among IPV survivors in Los Angeles County (LAC). We conducted 19 key informant interviews with various professionals working in domestic violence prevention in LAC. Factors such as survivors' motivation, ease of navigating the legal procedures, and availability of community resources facilitate the use of DVROs. Fear, ambivalence, structural barriers to access DVROs, and issues with the criminal justice system make it harder for survivors to obtain DVROs.

Ageing changes in retinal outer nuclear layer thickness and cone photoreceptor density using adaptive optics-free imaging.

PURPOSE: To investigate age-related changes of the outer nuclear layer (ONL) thickness and cone density, and their associations in healthy participants using a modified, narrow scan-angle Heidelberg Retina Angiograph (HRA2). METHODS: Retinal cones were imaged outside the fovea at 8.8° eccentricity and cone density was compared to ONL thickness measurements obtained by Spectral-Domain Optical Coherence Tomography (SD-OCT) at the same locations. Fifty-six eyes of 56 healthy participants with a median age (interquartile range, IQR) of 37 years (29-55) were included. RESULTS: Median (IQR) cone count was 7,472 (7,188, 7,746) cones/mm2 and median (IQR) ONL thickness was 56 (52, 60) µm for healthy participants. Both cone density and ONL thickness were negatively associated with age: cone density, R2 = 0.16 (F(1,54) = 10.41, P = 0.002); ONL thickness, R2 = 0.12 (F(1,54) = 7.41, P = 0.009). No significant association was seen between cone density and ONL thickness (R2 = 0.03; F(1,54) = 1.66, P = 0.20). CONCLUSION: Cone density was lower, and ONL thinner, in older compared to younger participants, therefore, image-based structural measures should be compared to age-related data. However, cone density and ONL thickness were not strongly associated, indicating that determinants of ONL thickness measurements other than cone density measurements, and including measurement error, have a major influence.

A Qualitative Investigation on COVID-19 Vaccine Hesitancy in Neurodivergent Communities.

Vaccine hesitancy is a major barrier to vaccination, hindering the success of vaccine efforts and thereby increasing public health risk to viral diseases, including COVID-19. Neurodivergent (ND) individuals, including individuals with an intellectual and/or developmental disability, have demonstrated a heightened risk of hospitalization and death due to COVID-19, highlighting the need for further research specifically on ND communities. We conducted a qualitative analysis using in-depth interviews with medical professionals, non-medical health professionals and communicators, and ND individuals or their caregivers. Using a thematic coding analysis methodology, trained coders identified major themes according to 24 distinct codes spanning across the categories of (1) barriers to vaccination; (2) facilitators to vaccination; and (3) suggestions for improving vaccine confidence. Qualitative findings identify misinformation, perception of vaccine risk, sensory sensitivities, and structural hardship as the most significant barriers to COVID-19 vaccination. We highlight the importance of accommodations to vaccination for the ND community alongside coordinated efforts by healthcare leaders to direct their communities to accurate sources of medical information. This work will inform the direction of future research on vaccine hesitancy, and the development of programs specific to the ND community's access to vaccines.

Trends in Influenza Vaccination Rates among a Medicaid Population from 2016 to 2021.

Seasonal influenza is a leading cause of death in the U.S., causing significant morbidity, mortality, and economic burden. Despite the proven efficacy of vaccinations, rates remain notably low, especially among Medicaid enrollees. Leveraging Medicaid claims data, this study characterizes influenza vaccination rates among Medicaid enrollees and aims to elucidate factors influencing vaccine uptake, providing insights that might also be applicable to other vaccine-preventable diseases, including COVID-19. This study used Medicaid claims data from nine U.S. states (2016-2021], encompassing three types of claims: fee-for-service, major Medicaid managed care plan, and combined. We included Medicaid enrollees who had an in-person healthcare encounter during an influenza season in this period, excluding those under 6 months of age, over 65 years, or having telehealth-only encounters. Vaccination was the primary outcome, with secondary outcomes involving in-person healthcare encounters. Chi-square tests, multivariable logistic regression, and Fisher's exact test were utilized for statistical analysis. A total of 20,868,910 enrollees with at least one healthcare encounter in at least one influenza season were included in the study population between 2016 and 2021. Overall, 15% (N = 3,050,471) of enrollees received an influenza vaccine between 2016 and 2021. During peri-COVID periods, there was an increase in vaccination rates among enrollees compared to pre-COVID periods, from 14% to 16%. Children had the highest influenza vaccination rates among all age groups at 29%, whereas only 17% were of 5-17 years, and 10% were of the 18-64 years were vaccinated. We observed differences in the likelihood of receiving the influenza vaccine among enrollees based on their health conditions and medical encounters. In a study of Medicaid enrollees across nine states, 15% received an influenza vaccine from July 2016 to June 2021. Vaccination rates rose annually, peaking during peri-COVID seasons. The highest uptake was among children (6 months-4 years), and the lowest was in adults (18-64 years). Female gender, urban residency, and Medicaid-managed care affiliation positively influenced uptake. However, mental health and substance abuse disorders decreased the likelihood. This study, reliant on Medicaid claims data, underscores the need for outreach services.

The Effect of Induced Intraocular Stray Light on Recognition Thresholds for Pseudo-High-Pass Filtered Letters.

Purpose: The Moorfields Acuity Chart (MAC)-comprising pseudo-high-pass filtered "vanishing optotype" (VO) letters-is more sensitive to functional visual loss in age-related macular degeneration (AMD) compared to conventional letter charts. It is currently unknown the degree to which MAC acuity is affected by optical factors such as cataract. This is important to know when determining whether an individual's vision loss owes more to neural or optical factors. Here we estimate recognition acuity for VOs and conventional letters with simulated lens aging, achieved using different levels of induced intraocular light scatter. Methods: Recognition thresholds were determined for two experienced and one naive participant with conventional and VO letters. Stimuli were presented either foveally or at 10 degrees in the horizontal temporal retina, under varying degrees of intraocular light scatter induced by white resin opacity-containing filters (WOFs grades 1 to 5). Results: Foveal acuity only became significantly different from baseline (no filter) for WOF grade 5 with conventional letters and WOF grades 4 and 5 with VOs. In the periphery, no statistical difference was found for any stray-light level for both conventional and VOs. Conclusions: Recognition acuity measured with conventional and VOs is robust to the effects of simulated lens opacification, and thus its higher sensitivity to neural damage should not simultaneously be confounded by such optical factors. Translational Relevance: The MAC may be better able to differentiate between neural and optical deficits of visual performance, making it more suitable for the assessment of patients with AMD, who may display both types of functional visual loss.

Preliminary clinical validation of a new picture-based visual acuity test in children with amblyopia: a comparison of The Auckland Optotypes and crowded logMAR letters.

BACKGROUND/AIMS: Amblyopia is the most common visual deficit in children and accurate visual acuity (VA) assessment is essential for diagnosis. While ETDRS high-contrast logMAR VA is the reference standard test for adults, less agreement exists for pre-literate children. A new picture optotype acuity test (The Auckland Optotypes [TAO]) has shown favourable comparison to letter acuity charts but has not yet been evaluated in children with amblyopia. This study aimed to compare VA obtained using TAO to crowded logMAR letters in children age 5-8 years with amblyopia. METHODS: Children with amblyopia (n = 54 [20.37% strabismic, 18.52% anisometropic, 61.11% mixed], mean age 78.30 ± 11.72 months) were recruited from paediatric ophthalmology/orthoptic clinics at Moorfields Eye Hospital NHS Foundation Trust, London, and Cambridge Community Services NHS Trust, Bedford. Best-corrected VA was measured in both the amblyopic eye (AE) and fellow eye (FE) using TAO and a crowded letter acuity chart. Bland-Altman analysis was used to measure 95% limits of agreement (LoA) for VA measures captured (AE, FE and interocular difference [IOD]). RESULTS: Good agreement between TAO and letter VA measurement was observed (mean bias: AE -0.01, FE 0.01, IOD -0.02). For AE measures 95% LoA were from -0.25 to 0.24 logMAR, this being similar for FE (-0.24 to 0.25) and IOD measures (-0.30 to 0.27). CONCLUSION: TAO and letters elicited similar VA in children with amblyopia. TAO could be a useful picture-based chart for paediatric vision assessment.

Vanishing Optotype acuity: repeatability and effect of the number of alternatives.

PURPOSE: Vanishing Optotype letters have a pseudo high-pass design so that the mean luminance of the target is the same as the background and the letters thus 'vanish' soon after the resolution threshold is reached. We wished to determine the variability of acuity measurements using these letters compared to conventional letters, and in particular how acuity is affected by the number of alternatives available to the subject. METHODS: Acuity was measured using high contrast letters of both conventional and Vanishing Optotype design for three experienced normal subjects. Thresholds were determined for central vision in a forced choice paradigm for two alternatives (2AFC; AU and OQ), 4AFC (AQUO), 6AFC (QUANGO) and 26AFC (whole alphabet) using a QUEST procedure. Three measurements were made for each condition. RESULTS: Threshold letter size was always larger for the Vanishing Optotypes than conventional letters, although the size of this difference (0.11-0.34 logMAR) depended on the number of alternatives and what they were. The effect of the number of AFC, and the individual letters employed, was smaller for the Vanishing Optotypes, implying that they are more equally legible than conventional optotypes. Variability was also lower for the Vanishing Optotype sets (0.01-0.03 logMAR) than the conventional letter sets (0.03-0.06). CONCLUSIONS: The smaller effect of the number of letter alternatives, combined with more equal discriminability and lower threshold variability, implies that Vanishing Optotypes may be appropriate targets from which to design letter charts to measure small clinical changes in acuity.

Can Visual Acuity Be Reliably Measured at Home? Validation of Telemedicine Remote Computerised Visual Acuity Measurements.

PURPOSE: The recent pandemic has identified the need for telemedicine assessment of ophthalmology patients. A vital component of such assessment is visual acuity (VA) measurement. The aim of this study was to determine the feasibility and reliability of computerised 'at home' VA measurements using COMPlog software. METHODS: A Bland Altman method comparison study of worse eye 'in clinic' and 'at home' orthoptist-supervised COMPlog computerised VA measurements. Subjects underwent gold standard semi-automated computerised test and retest logMAR VA measurements on their habitually corrected worse eye both 'in clinic' and 'at home.' The orthoptist ran the test from the eye clinic with the patient viewing a secondary PC monitor either in the same clinic room or at home. A screen sharing voice and video conferencing application and standard consumer IT hardware were employed to present the test optotypes in the patient's home. RESULTS: 23 paediatric and 13 adult patients with a range of ocular diseases and worse eye visual acuities were included (range -0.14 to 1.06 logMAR). No significant bias was found between 'in clinic' and 'at home' measurements (mean -0.01 logMAR and 95% confidence interval -0.03, 0.00 logMAR). Test-retest variability of 'in clinic,' 'at home' and 'in clinic' versus 'at home' measurements were within normal reported ranges at 0.12 logMAR (6 ETDRS letters) or less. CONCLUSION: Remote home VA testing performed by an eye care professional using a semi-automated VA measurement program and video conferencing application provided unbiased measurements with acceptable test-retest reliability. Home testing was both feasible and acceptably reliable in appropriately equipped patients.

Effect of letter separation on computerised visual acuity measurements: comparison with the gold standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart.

Contour interaction plays an important role in letter recognition and has long been known to influence clinical visual acuity measurements. LogMAR charts originally employed between-letter and line spacing of one letter width/height; however, in more recent designs, half letter width spacing has become accepted without validation. COMPlog is a computerised visual acuity measurement device being developed and validated for routine and research clinical use and is available commercially. This study was performed to investigate the effect of letter separation on computerised visual acuity measurements. An iterative series of experiments was performed in which test and retest fully interpolated five letters-per-line logMAR visual acuity measurements were taken in three groups of a total 100 adult subjects. Each group had visual acuity measured using ETDRS charts 1 and 2 and on COMPlog using various combinations of letter and line spacing. The first group consisted of 31 subjects tested using 3.75 and 2.50 stroke width spacing, the second 45 subjects using 2.50 and 1.25 stroke width spacing and the last group, 24 subjects tested using 1.90 stroke width spacing. The methods of Bland and Altman were used to analyse the data. No significant bias was noted between the gold standard ETDRS measurements and those taken using COMPlog with 3.75 stroke width spacing. Significant bias of half a logMAR line was found with crowding of 1.90 and 1.25 stroke widths. A small systematic bias with a reduction of 1 ETDRS letter was found with spacing of 2.50 stroke widths which has not been demonstrated in previous validation studies. Crowding of 2.50 stroke widths is the smallest spacing which can be used in the design of COMPlog.

Visual acuity loss in patients with age-related macular degeneration measured using a novel high-pass letter chart.

BACKGROUND/AIMS: Conventional Logarithm of the Minimum Angle of Resolution (logMAR) acuity is the current gold standard for assessing visual function in age-related macular degeneration (AMD). However, visual acuity (VA) often remains 'normal' when measured with these charts, even with advanced retinal changes. We wished to investigate how VA measurements with the Moorfields Acuity Chart (MAC), which employs high-pass filtered letters, compares to conventional letter charts in subjects with AMD. METHODS: Monocular best-corrected VA measurements and test-retest variability (TRV) were compared for conventional and MAC charts in 38 normal observers (mean age 52.1 years) and 80 patients (mean age 80.6 years) with varying degrees of acuity loss owing to AMD. Methods of Bland-Altman and ordinary least-squares regression were employed for data analysis. RESULTS: A proportional bias was confirmed between conventional and MAC measurements (r(2)=0.133, p=0.001) such that MAC acuity was -0.45 logMAR 'worse' at the 0.00 logMAR acuity level, but only -0.26 logMAR 'worse' at the 1.00 logMAR level. The mean bias was much smaller in the normal subject group (-0.16 logMAR). Similar TRV (ranging from ±0.09 to ±0.12 logMAR) was found for both charts in both subject groups. CONCLUSIONS: VA measurements with the MAC chart appear to be more sensitive to functional loss in AMD compared with conventional letter charts, with similar TRV. Simulations indicate this may be because the high-pass filtered letters are more vulnerable to undersampling as a result of retinal cell loss in the disease process.

Effect of scoring and termination rules on test-retest variability of a novel high-pass letter acuity chart.

PURPOSE: Test-retest variability (TRV) limits our ability to detect clinically significant changes in visual acuity (VA). We wanted to compare the effect of scoring and termination rules on TRV for logMAR charts, employing either conventional or pseudo high-pass (Vanishing Optotype) letters. METHODS: VA measurements and TRV were compared in 50 uncorrected normal observers (17 male, mean age 42.8 ± 16.2 years) using both conventional logMAR-style charts and letter charts of the same layout but containing pseudo high-pass letters (Moorfields Acuity Chart [MAC]). Additional charts employing a different 10-letter alphabet to the Sloan set were also tested. Mean spherical refractive error was -0.93 diopters (D; range, -5.38 to +3.00 D). Acuity scores were calculated using three methods: letter-by-letter, with either line- or chart-based termination, and line-by-line scoring. Bland-Altman methods were used to calculate 95% ranges for TRV. RESULTS: While acuity thresholds were higher for the MAC, they were less affected by termination criteria and displayed significantly lower 95% TRV values across all scoring techniques. Ordinary least squares regression analysis confirmed a proportional as well as systematic bias between conventional and MAC measurements (r(2) = 0.217, P = 0.001) such that the difference between the two was greater with better VA. CONCLUSIONS: TRV was consistently lower for a logMAR chart employing high-pass rather than conventional letters in uncorrected refractive error and was less affected by termination and scoring methods. The MAC was also less affected by optical defocus. Further work is required to determine the usefulness of different charts to differentiate between optical and neural losses of vision.

Effect of optical defocus on detection and recognition of vanishing optotype letters in the fovea and periphery.

PURPOSE: Vanishing optotypes (VOs) are pseudo high-pass letters whose mean luminance matches the background so that they "vanish" when the recognition acuity threshold is reached in the fovea. We determined the effect of increasing blur on acuity for these optotypes and conventional letters, in both foveal and extrafoveal viewing. METHODS: Detection and recognition thresholds were determined separately for each of the 26 letters of both a conventional and VO alphabet, both in the fovea and at 10° in the horizontal temporal retina, under varying degrees of positive dioptric blur. RESULTS: In the fovea, detection and recognition thresholds were similar for individual VOs, increased steadily with blur, and separated somewhat at higher levels of defocus (3 diopters [D]). While the recognition thresholds for VOs changed on average by 0.28 logarithm of the minimum angle of resolution (logMAR)/D, those for conventional letters changed more rapidly by 0.35 logMAR/D. In the periphery, recognition thresholds were significantly higher than detection thresholds for the VOs at 0 D blur; both thresholds increased steadily thereafter, converging as blur increased. Peripheral recognition acuity displayed a loss of only 0.09 logMAR/D. In both the fovea and periphery, the interletter variation in recognition acuity was much lower for VOs than conventional letters (0.04 vs. 0.09 logMAR). CONCLUSIONS: Outside the fovea, high-pass VOs display significant differences in their detection and resolution thresholds up to +7 D blur, with a logMAR/D loss of a quarter that of the fovea. The lower interletter legibility differences indicate that VO letters may be better stimuli from which to design clinical letter charts.

Computerized repeating and averaging improve the test-retest variability of ETDRS visual acuity measurements: implications for sensitivity and specificity.

PURPOSE: The goals of this study were to investigate the effectiveness of computerized repeating and averaging of visual acuity measurements in reducing test-retest variability (TRV) and to estimate the increase in sensitivity and specificity that would be achieved in diagnosing visual acuity change. METHODS: Timed, paired ETDRS chart and computerized acuity mean measurement (CAMM) were performed in 100 subjects. CAMM(n) scores were the running mean of consecutive measurements. Bland-Altman methods were used to calculate 95% ranges for TRV. RESULTS: The 95% TRV range of ETDRS measurements and the CAMM score after 6 (CAMM6) measurements were, respectively, 8 and 5.7 ETDRS letters (P = 0.02). CAMM6 offered a pragmatically optimum tradeoff between reduced TRV and test time. A measured change of 5 letters or more in the absence of true change was observed in 13% (95% CI, 8%-21%) with the ETDRS chart and 4% (95% CI, 2%-10%) with CAMM6 measurements. To achieve ≥95% test sensitivity (assuming 95% test specificity), change criteria of 15 and 11 letters must be set with an ETDRS chart and CAMM6, respectively. CAMM6 measurement times were longer (mean 234 seconds vs. 74 seconds) for the ETDRS chart. CONCLUSIONS: Compared with the current gold standard, computerized repeating and averaging of acuity measurements improve specificity and sensitivity when identifying true changes. The 160-second increase in test time should be set against the considerable economic and clinical benefits that may result.