Investigating the linkage between mesopic spatial summation and variations in retinal ganglion cell density across the central visual field

PURPOSE: The relationship between perimetric stimulus area and Ricco's area (RA) determines measured thresholds and the sensitivity of perimetry to retinal disease. The nature of this relationship, in addition to effect of retinal ganglion cell (RGC) number on this, is currently unknown for the adaptation conditions of mesopic microperimetry. In this study, achromatic mesopic spatial summation was measured across the central visual field to estimate RA with the number of RGCs underlying RA also being established. METHODS: Achromatic luminance thresholds were measured for six incremental spot stimuli (0.009-2.07 deg2 ) and 190.4 ms duration, at four locations, each at 2.5°, 5° and 10° eccentricity in five healthy observers (mean age 61.4 years) under mesopic conditions (background 1.58 cd/m2 ). RA was estimated using two-phase regression analysis with the number of RGCs underlying RA being calculated using normative histological RGC counts. RESULTS: Ricco's area exhibited a small but statistically insignificant increase between 2.5° and 10° eccentricity. Compared with photopic conditions, RA was larger, with the difference between RA and the Goldmann III stimulus (0.43°) being minimised. RGC number underlying RA was also higher than reported for photopic conditions (median 70 cells, IQR 36-93), with no significant difference being observed across test locations. CONCLUSIONS: Ricco's area and the number of RGCs underlying RA do not vary significantly across the central visual field in mesopic conditions. However, RA is larger and more similar to the standard perimetric Goldmann III stimulus under mesopic compared with photopic adaptation conditions. Further work is required to determine if compensatory enlargements in RA occur in age-related macular degeneration, to establish the optimal stimulus parameters for AMD-specific microperimetry

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

Spatiotemporal summation of perimetric stimuli in healthy observers

Spatial summation of perimetric stimuli has been used to derive conclusions about the spatial extent of retinal-cortical convergence, mostly from the size of the critical area of summation (Ricco's area, RA) and critical number of retinal ganglion cells (RGCs). However, spatial summation is known to change dynamically with stimulus duration. Conversely, temporal summation and critical duration also vary with stimulus size. Such an important and often neglected spatiotemporal interaction has important implications for modeling perimetric sensitivity in healthy observers and for formulating hypotheses for changes measured in disease. In this work, we performed experiments on visually heathy observers confirming the interaction of stimulus size and duration in determining summation responses in photopic conditions. We then propose a simplified computational model that captures these aspects of perimetric sensitivity by modelling the total retinal input, the combined effect of stimulus size, duration, and retinal cones-to-RGC ratio. We additionally show that, in the macula, the enlargement of RA with eccentricity might not correspond to a constant critical number of RGCs, as often reported, but to a constant critical total retinal input. We finally compare our results with previous literature and show possible implications for modeling disease, especially glaucoma

Spatial summation in the glaucomatous macula: a link with retinal ganglion cell damage

Purpose: to test whether functional loss in the glaucomatous macula is characterised by an enlargement of Ricco’s area (RA) through the application of a computational model linking retinal ganglion cell (RGC) damage to perimetric sensitivity Methods: one eye from each of 29 visually-healthy subjects <40 years old, 30 glaucoma patients and 20 age-similar controls was tested with a 10-2 grid with stimuli of five different area sizes. Structural estimates of point-wise RGC density were obtained from Optical Coherence Tomography scans. Structural and functional data from the young healthy cohort were used to estimate the parameters of a computational spatial summation model to generate a template. The template was fitted with a Bayesian hierarchical model to estimate the latent RGC density in glaucoma patients and agematched controls. We tested two alternative hypotheses: fitting the data by translating the template horizontally (H1: change in RA) or vertically (H2: loss of sensitivity without change in RA). Root Mean Squared Error (RMSE) of the model fits to perimetric sensitivity were compared. 95%-Confidence Intervals were bootstrapped. The dynamic range of the functional and structural RGC density estimates was denoted by their 1st and the 99th percentile. Results: the RMSE was 2.09 [1.92-2.26] under H1 and 2.49 [2.24-2.72] under H2 (p < 0.001). The average dynamic range for the structural RGC density estimates was only 11% that of the functional estimates. Conclusions: macular sensitivity loss in glaucoma is better described by a model in which RA changes with RGC loss. Structural measurements have limited dynamic range

The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK

To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)'s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy. Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them. In total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases). A decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease. [Abstract copyright: © 2024. The Author(s).

Ophthalmology research in the UK’s National Health Service: the structure and performance of the NIHR’s Ophthalmology research portfolio

Purpose- To report on the composition and performance of the portfolio of Ophthalmology research studies in the United Kingdom’s National Institute for Health Research (NIHR) Clinical Research Network (UK CRN). Methods- Ophthalmology studies open to recruitment between 1 April 2010 and 31 March 2018 were classified by: sub-specialty, participant age, gender of Chief Investigator, involvement of genetic investigations, commercial/ non-commercial, interventional/observational design. Frequency distributions for each covariate and temporal variation in recruitment to time and target were analysed. Results- Over 8 years, 137,377 participants were recruited (average of 15,457 participants/year; range: 5485–32,573) with growth by year in proportion of commercial studies and hospital participation in England (76% in 2017/18). Fourteen percent of studies had a genetic component and most studies (82%) included only adults. The majority of studies (41%) enrolled patients with retinal diseases, followed by glaucoma (17%), anterior segment and cataract (13%), and ocular inflammation (6%). Overall, 68% of non-commercial studies and 55% of commercial studies recruited within the anticipated time set by the study and also recruited to or exceeded the target number of participants. Conclusions- High levels of clinical research activity, growth and improved performance have been observed in Ophthalmology in UK over the past 8 years. Some sub-specialties that carry substantial morbidity and a very high burden on NHS services are underrepresented and deserve more patient-centred research. Yet the NIHR and its CRN Ophthalmology National Specialty Group has enabled key steps in achieving the goal of embedding research into every day clinical care

The appropriateness of luminance vs. energy as a descriptor of CRT stimulus output when measuring the temporal aspects of vision

The use of cathode-ray-tube monitors is widespread in the vision science community. The temporal response of these displays is, however, known to vary with the frame rate selected. No previous study has investigated if variations in frame rate impacts upon the temporal processing of spatially identical stimuli. In this study we found the upper limit of complete temporal summation for an achromatic spot stimulus to be greater at 60Hz compared with a frame rate of 160Hz when visual thresholds were classified using luminance output. No such variation was found when a novel metric quantifying total energy output was used. This finding has significant implications for the accurate quantification of visual thresholds collected using display monitors used in visual psychophysics investigations

Machine Learning Algorithms to Detect Subclinical Keratoconus: Systematic Review

BACKGROUND: Keratoconus is a disorder characterized by progressive thinning and distortion of the cornea. If detected at an early stage, corneal collagen cross-linking can prevent disease progression and further visual loss. Although advanced forms are easily detected, reliable identification of subclinical disease can be problematic. Several different machine learning algorithms have been used to improve the detection of subclinical keratoconus based on the analysis of multiple types of clinical measures, such as corneal imaging, aberrometry, or biomechanical measurements. OBJECTIVE: The aim of this study is to survey and critically evaluate the literature on the algorithmic detection of subclinical keratoconus and equivalent definitions. METHODS: For this systematic review, we performed a structured search of the following databases: MEDLINE, Embase, and Web of Science and Cochrane Library from January 1, 2010, to October 31, 2020. We included all full-text studies that have used algorithms for the detection of subclinical keratoconus and excluded studies that did not perform validation. This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. RESULTS: We compared the measured parameters and the design of the machine learning algorithms reported in 26 papers that met the inclusion criteria. All salient information required for detailed comparison, including diagnostic criteria, demographic data, sample size, acquisition system, validation details, parameter inputs, machine learning algorithm, and key results are reported in this study. CONCLUSIONS: Machine learning has the potential to improve the detection of subclinical keratoconus or early keratoconus in routine ophthalmic practice. Currently, there is no consensus regarding the corneal parameters that should be included for assessment and the optimal design for the machine learning algorithm. We have identified avenues for further research to improve early detection and stratification of patients for early treatment to prevent disease progression

The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK

To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)'s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy. Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them. In total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases). A decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease