PallorMetrics: Software for Automatically Quantifying Optic Disc Pallor in Fundus Photographs, and Associations With Peripapillary RNFL Thickness.

Purpose: We sough to develop an automatic method of quantifying optic disc pallor in fundus photographs and determine associations with peripapillary retinal nerve fiber layer (pRNFL) thickness. Methods: We used deep learning to segment the optic disc, fovea, and vessels in fundus photographs, and measured pallor. We assessed the relationship between pallor and pRNFL thickness derived from optical coherence tomography scans in 118 participants. Separately, we used images diagnosed by clinical inspection as pale (n = 45) and assessed how measurements compared with healthy controls (n = 46). We also developed automatic rejection thresholds and tested the software for robustness to camera type, image format, and resolution. Results: We developed software that automatically quantified disc pallor across several zones in fundus photographs. Pallor was associated with pRNFL thickness globally (ß = -9.81; standard error [SE] = 3.16; P < 0.05), in the temporal inferior zone (ß = -29.78; SE = 8.32; P < 0.01), with the nasal/temporal ratio (ß = 0.88; SE = 0.34; P < 0.05), and in the whole disc (ß = -8.22; SE = 2.92; P < 0.05). Furthermore, pallor was significantly higher in the patient group. Last, we demonstrate the analysis to be robust to camera type, image format, and resolution. Conclusions: We developed software that automatically locates and quantifies disc pallor in fundus photographs and found associations between pallor measurements and pRNFL thickness. Translational Relevance: We think our method will be useful for the identification, monitoring, and progression of diseases characterized by disc pallor and optic atrophy, including glaucoma, compression, and potentially in neurodegenerative disorders.

Artificial Intelligence in Anterior Chamber Evaluation: A Systematic Review and Meta-analysis.

PRCIS: In this meta-analysis of 6 studies and 5,269 patients, deep learning algorithms applied to AS-OCT demonstrated excellent diagnostic performance for closed-angle compared to gonioscopy, with a pooled sensitivity and specificity of 94% and 93.6%, respectively. PURPOSE: This study aimed to review the literature and compare the accuracy of deep learning algorithms (DLA) applied to anterior segment optical coherence tomography images (AS-OCT) against gonioscopy in detecting angle-closure in patients with glaucoma. METHODS: We performed a systematic review and meta-analysis evaluating DLA in AS-OCT images for the diagnosis of angle closure compared with gonioscopic evaluation. PubMed, Scopus, Embase, Lilacs, Scielo, and Cochrane Central Register of Controlled Trials were searched. The bivariate model was used to calculate pooled sensitivity and specificity. RESULTS: The initial search identified 214 studies, of which 6 were included for final analysis. The total study population included 5,269 patients. The combined sensitivity of the DLA compared with gonioscopy was 94.0% (95% CI 83.8%-97.9%), whereas the pooled specificity was 93.6% (95% CI 85.7%-97.3%). Sensitivity analyses removing each individual study showed a pooled sensitivity in the range of 90.1% to 95.1%. Similarly, specificity results ranged from 90.3 to 94.5% with the removal of each individual study and recalculation of pooled specificity. CONCLUSION: DLA applied to AS-OCT has excellent sensitivity and specificity in the identification of angle closure. This technology may be a valuable resource in the screening of populations without access to experienced ophthalmologists who perform gonioscopy.

Factors associated with pathologic myopia onset and progression: A systematic review and meta-analysis.

PURPOSE: To synthesise evidence across studies on factors associated with pathologic myopia (PM) onset and progression based on the META-analysis for Pathologic Myopia (META-PM) classification framework. METHODS: Findings from six longitudinal studies (5-18 years) were narratively synthesised and meta-analysed, using odds ratio (OR) as the common measure of association. All studies adjusted for baseline myopia, age and sex at a minimum. The quality of evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation framework. RESULTS: Five out of six studies were conducted in Asia. There was inconclusive evidence of an independent effect (or lack thereof) of ethnicity and sex on PM onset/progression. The odds of PM onset increased with greater axial length (pooled OR: 2.03; 95% CI: 1.71-2.40; p < 0.001), older age (pooled OR: 1.07; 1.05-1.09; p < 0.001) and more negative spherical equivalent refraction, SER (OR: 0.77; 0.68-0.87; p < 0.001), all of which were supported by an acceptable level of evidence. Fundus tessellation was found to independently increase the odds of PM onset in a population-based study (OR: 3.02; 2.58-3.53; p < 0.001), although this was only supported by weak evidence. There was acceptable evidence that greater axial length (pooled OR: 1.23; 1.09-1.39; p < 0.001), more negative SER (pooled OR: 0.87; 0.83-0.92; p < 0.001) and higher education level (pooled OR: 3.17; 1.36-7.35; p < 0.01) increased the odds of PM progression. Other baseline factors found to be associated with PM progression but currently supported by weak evidence included age (pooled OR: 1.01), severity of myopic maculopathy (OR: 3.61), intraocular pressure (OR: 1.62) and hypertension (OR: 0.21). CONCLUSIONS: Most PM risk/prognostic factors are not supported by an adequate evidence base at present (an indication that PM remains understudied). Current factors for which an acceptable level of evidence exists (limited in number) are unmodifiable in adults and lack personalised information. More longitudinal studies focusing on uncovering modifiable factors and imaging biomarkers are warranted.

Novel linkage approach to join community-acquired and national data.

BACKGROUND: Community optometrists in Scotland have performed regular free-at-point-of-care eye examinations for all, for over 15 years. Eye examinations include retinal imaging but image storage is fragmented and they are not used for research. The Scottish Collaborative Optometry-Ophthalmology Network e-research project aimed to collect these images and create a repository linked to routinely collected healthcare data, supporting the development of pre-symptomatic diagnostic tools. METHODS: As the image record was usually separate from the patient record and contained minimal patient information, we developed an efficient matching algorithm using a combination of deterministic and probabilistic steps which minimised the risk of false positives, to facilitate national health record linkage. We visited two practices and assessed the data contained in their image device and Practice Management Systems. Practice activities were explored to understand the context of data collection processes. Iteratively, we tested a series of matching rules which captured a high proportion of true positive records compared to manual matches. The approach was validated by testing manual matching against automated steps in three further practices. RESULTS: A sequence of deterministic rules successfully matched 95% of records in the three test practices compared to manual matching. Adding two probabilistic rules to the algorithm successfully matched 99% of records. CONCLUSIONS: The potential value of community-acquired retinal images can be harnessed only if they are linked to centrally-held healthcare care data. Despite the lack of interoperability between systems within optometry practices and inconsistent use of unique identifiers, data linkage is possible using robust, almost entirely automated processes.

European Glaucoma Society research priorities for glaucoma care.

BACKGROUND/AIMS: The goal of health research is to improve patients care and outcomes. Thus, it is essential that research addresses questions that are important to patients and clinicians. The aim of this study was to develop a list of priorities for glaucoma research involving stakeholders from different countries in Europe. METHODS: We used a three-phase method, including a two-round electronic Delphi survey and a workshop. The clinician and patient electronic surveys were conducted in parallel and independently. For phase I, the survey was distributed to patients from 27 European countries in 6 different languages, and to European Glaucoma Society members, ophthalmologists with expertise in glaucoma care, asking to name up to five research priorities. During phase II, participants were asked to rank the questions identified in phase I using a Likert scale. Phase III was a 1 day workshop with patients and clinicians. The purpose was to make decisions about the 10 most important research priorities using the top 20 priorities identified by patients and clinicians. RESULTS: In phase I, 308 patients and 150 clinicians were involved. In phase II, the highest-ranking priority for both patients and clinicians was 'treatments to restore vision'. In phase III, eight patients and four clinicians were involved. The top three priorities were 'treatments to stop sight loss', 'treatments to restore vision' and 'improved detection of worsening glaucoma'. CONCLUSION: We have developed a list of priorities for glaucoma research involving clinicians and patients from different European countries that will help guide research efforts and investment.

Cannabis use and the risk of primary open-angle glaucoma: a Mendelian randomization study.

Several observational studies have investigated the association between cannabis use and intraocular pressure, but its association with primary open-angle glaucoma (POAG) remains unclear. In this study, we leveraged human genetic data to assess through Mendelian randomization (MR) whether cannabis use affects POAG. We used five single-nucleotide polymorphisms (SNPs) associated with lifetime cannabis use (P-value < 5 × 10-8) from a genome-wide association study (GWAS) (N = 184,765) by the International Cannabis Consortium, 23andMe, and UK Biobank and eleven SNPs associated with cannabis use disorder (P-value < 5 × 10-7) from a GWAS meta-analysis of (17,068 cases and 357,219 controls of European descent) from Psychiatric Genomics Consortium Substance Use Disorders working group, Lundbeck Foundation Initiative for Integrative Psychiatric Research, and deCode. We associated the selected five SNPs from the GWAS of lifetime cannabis use and the eleven SNPs from the GWAS of cannabis use disorder, with the largest to date GWAS meta-analysis of POAG (16,677 cases and 199,580 controls). MR analysis suggested no evidence for a causal association of lifetime cannabis use and cannabis use disorder with POAG (odds ratio (OR) of outcome per doubling of the odds of exposure (95% confidence interval): 1.04 (0.88; 1.23) for lifetime cannabis use and 0.97 (0.92; 1.03) for cannabis use disorder). Sensitivity analyses to address pleiotropy and weak instrument bias yielded similar estimates to the primary analysis. In conclusion, our results do not support a causal association between cannabis use and POAG.

The Royal College of Ophthalmologists' National Ophthalmology Database study of cataract surgery: report 16, influence of remuneration model on choice of intraocular lens in the UK.

BACKGROUND/OBJECTIVES: Cataract surgery with intraocular lens (IOL) implantation is one of the most commonly performed surgeries worldwide. Within the UK, publicly funded cataract surgery is remunerated by two models: (1) "block contract" (BC), which commissions organisations to deliver whole service pathways without considering specific activity items; or (2) "payment by results" (PbR), which pays a tariff price for each procedure. This study aimed to examine the association between remuneration model and the cost and types of IOL used. SUBJECTS/METHODS: Cataract operations recorded on the Royal College of Ophthalmologists' National Ophthalmology Database were included, with additional data collected for remuneration model from NHS England and cost of IOL from the NHS Spend Comparison Service. RESULTS: We included 907,052 cataract operations from 87 centres. The majority of operations were performed in PbR centres (456 198, 50.3%), followed by BC centres (240 641, 26.5%) and mixed models centres (210 213, 23.2%). The mean price of hydrophobic (n = 7) and hydrophilic IOLs (n = 5) were £45.72 and £42.86, respectively. Hydrophobic IOLs were predominantly used (650 633, 71.7%) and were significantly more commonly used in centres remunerated by BC (96.5% vs. 3.5%) than those by PbR (65.7% vs. 34.3%) when compared to hydrophilic IOLs (p < 0.001). CONCLUSIONS: This study demonstrated that the IOL choice may be perversely incentivised by the IOL cost and remuneration model. Although hydrophobic IOLs are more expensive at the point of surgery, their potential longer-term cost-effectiveness due to reduced requirement for YAG capsulotomy should be considered.

Feasibility of Automated Gonioscopy Imaging in Clinical Practice.

PRCIS: Automated gonioscopy provided good-quality images of the anterior chamber angle. There was a short learning curve for operators, and the examination was well tolerated by patients. Patients expressed a preference for automated gonioscopy compared with traditional gonioscopy. PURPOSE: The purpose of this study was to assess the feasibility of using a desktop automated gonioscopy camera in glaucoma clinics by examining patient tolerability, ease of use, and image quality and comparing patient preference compared with traditional gonioscopy. PATIENTS AND METHODS: A prospective study was conducted in a university hospital clinic. Traditional gonioscopy was performed followed by imaging of the iridocorneal angle (ICA) using the Nidek GS-1 camera by 2 glaucoma specialists. Participants were asked to rate the comfort of automated gonioscopy and which method they preferred. The clinicians graded the ease of acquisition for each patient, and the image quality was reviewed by a grader. RESULTS: Forty-three eyes of 25 participants were included. Sixty-eight percent of participants viewed automated gonioscopy as "extremely comfortable," and the remainder reported it "comfortable". Forty percent preferred automated gonioscopy compared with traditional gonioscopy, while 52% were equivocal. Clinicians scored 32% of participants as "somewhat difficult" to the image. In 46% of eyes, good-quality photographs were obtained for 360 degrees of the ICA. Only 1 eye had no parts of the ICA clearly visible. Seventy-four percent of eyes had at least half of the ICA clearly visible in all 4 quadrants. CONCLUSION: Automated gonioscopy provided good-quality images of the ICA for most patients. It was often not possible to image the entire 360 degrees at the first attempt, but the examination was comfortable for patients, and only 8% preferred traditional gonioscopy to the automated photographic examination.

The relationship between multiple deprivation and severity of glaucoma at diagnosis.

BACKGROUND: Socioeconomic deprivation is associated with higher odds of chronic diseases, with many individuals living with more than one illness. This study aimed to examine the relationship between deprivation and severity of glaucoma at diagnosis, an important risk factor for glaucoma blindness. METHODS: A retrospective study of 472 consecutive patients referred by community optometrists to the glaucoma clinic at a university hospital was performed. Glaucoma severity was determined by standard automated perimetry mean deviation (MD) in the worse eye. The Scottish Index of Multiple Deprivation (SIMD) was determined for each patient as a measure of deprivation based on postcode. Regression analyses were performed to determine the relationship between visual field MD and SIMD. RESULTS: There was a significant relationship between higher levels of deprivation (lower SIMD) and worse severity of glaucoma at diagnosis. 32 of 472 patients (6.8%) had a MD of ≤-6 dB and 11 (2.3%) ≤-12 dB in their better eye. MD in the worse eye was 0.04 dB (95% CI 0.014 to 0.062 dB, P = 0.002) worse for each 100-point decrease in SIMD, with lower SIMD indicating a higher level of deprivation. A higher proportion of patients living in most deprived areas had a MD ≤ -6 dB or ≤ -12 dB at presentation compared to those living in the least deprived areas (14.3% versus 6.8% for ≤ -6 dB and 4.8% versus 0.8% for ≤ -12 dB). CONCLUSIONS: Higher levels of deprivation were associated with worse glaucoma severity at presentation. The reasons for poorer outcomes in those from more deprived communities need further study so that inequalities can be addressed and the frequency of patients presenting with advanced glaucoma reduced.

Teaching home tonometry using a remote video link.

BACKGROUND/OBJECTIVES: Intraocular pressure (IOP) is the primary modifiable risk factor in the progression of glaucoma. The ICare HOME is a self-tonometer which empowers patients to measure their own IOP and allows a more complete picture of diurnal IOP. This project aims to determine the feasibility of teaching patients to perform self-tonometry remotely using a remote video link. SUBJECTS/METHODS: This prospective study involved 12 patients with glaucoma attending an outpatient ophthalmology clinic. Participants were provided with a rebound tonometer (Icare HOME) and instructions to attend remote teaching from home. An optometrist conducted a 30 min live video training session via NearMe with each patient. Following training, participants were asked to measure their own IOP, observed remotely by the optometrist. Successful participants were asked to take a series of home IOP measurements over 48 h. Questionnaires were used to evaluate perceptions on home tonometry and remote training. RESULTS: Participants had an average age of 60.1 ± 15.5 years. 58% (7 of 12) were female. 83% (10 of 12) obtained successful diurnal measurements at home. All participants were happy with remote teaching, and none would have preferred training to be conducted face-to-face. All participants were interested in continuing home IOP monitoring. CONCLUSIONS: Most patients were able to perform home tonometry successfully when taught remotely, with a success rate similar to previously reported rates for face-to-face teaching using the same device. Most participants were receptive to using video calling as a platform for teaching home tonometry.

Adherence to topical glaucoma therapy in patients attending virtual clinics.

BACKGROUND/OBJECTIVES: Poor adherence to medical therapy is a major challenge to the effective treatment of chronic diseases including glaucoma. Potential factors influencing adherence include treatment complexity and patient understanding of disease and health beliefs. An increasing number of patients are seen in virtual clinics, where there is no face-to-face consultation, potentially reducing opportunities for patient education and reinforcement of the importance of treatment. The aim of this study was to examine adherence among patients attending a virtual glaucoma clinic. METHODS: 100 consecutive patients attending the virtual clinic were surveyed, with 78 using topical medications included in the analysis. All patients completed a validated adherence questionnaire with a score of >2 defined as poor adherence. The relationship between adherence and age, sex, duration since diagnosis, and disease severity was examined. RESULTS: The mean age was 73.1 ± 13.4 years, with an average mean deviation of -5.9 ± 5.5 dB and duration since first diagnosis of 9.0 ± 5.7 years. 93.6% reported self-instilling eye drops. Seventy-one patients (91.0 %) had good self-reported adherence. Multivariate logistic regression revealed those instilling eye drops independently had higher odds of good adherence. CONCLUSIONS: The level of medication adherence in the virtual glaucoma clinic was higher than adherence in previous studies examining patients attending face-to-face clinics. Virtual clinics should incorporate methods to ensure effective two-way communication with patients and strategies for patient education.

Measuring axial length of the eye from magnetic resonance brain imaging.

BACKGROUND: Metrics derived from the human eye are increasingly used as biomarkers and endpoints in studies of cardiovascular, cerebrovascular and neurological disease. In this context, it is important to account for potential confounding that can arise from differences in ocular dimensions between individuals, for example, differences in globe size. METHODS: We measured axial length, a geometric parameter describing eye size from T2-weighted brain MRI scans using three different image analysis software packages (Mango, ITK and Carestream) and compared results to biometry measurements from a specialized ophthalmic instrument (IOLMaster 500) as the reference standard. RESULTS: Ninety-three healthy research participants of mean age 51.0 ± SD 5.4 years were analyzed. The level of agreement between the MRI-derived measurements and the reference standard was described by mean differences as follows, Mango - 0.8 mm; ITK - 0.5 mm; and Carestream - 0.1 mm (upper/lower 95% limits of agreement across the three tools ranged from 0.9 mm to - 2.6 mm). Inter-rater reproducibility was between - 0.03 mm and 0.45 mm (ICC 0.65 to 0.93). Intra-rater repeatability was between 0.0 mm and - 0.2 mm (ICC 0.90 to 0.95). CONCLUSIONS: We demonstrate that axial measurements of the eye derived from brain MRI are within 3.5% of the reference standard globe length of 24.1 mm. However, the limits of agreement could be considered clinically significant. Axial length of the eye obtained from MRI is not a replacement for the precision of biometry, but in the absence of biometry it could provide sufficient accuracy to act as a proxy. We recommend measuring eye axial length from MRI in studies that do not have biometry but use retinal imaging to study neurodegenerative changes so as to control for differing eye size across individuals.

2D alpha-shapes to quantify retinal microvasculature morphology and their application to proliferative diabetic retinopathy characterisation in fundus photographs.

The use of 2D alpha-shapes (α-shapes) to quantify morphological features of the retinal microvasculature could lead to imaging biomarkers for proliferative diabetic retinopathy (PDR). We tested our approach using the MESSIDOR dataset that consists of colour fundus photographs from 547 healthy individuals, 149 with mild diabetic retinopathy (DR), 239 with moderate DR, 199 pre-PDR and 53 PDR. The skeleton (centrelines) of the automatically segmented retinal vasculature was represented as an α-shape and the proposed parameters, complexity ([Formula: see text]), spread (OpA), global shape (VS) and presence of abnormal angiogenesis (Gradα) were computed. In cross-sectional analysis, individuals with PDR had a lower [Formula: see text], OpA and Gradα indicating a vasculature that is more complex, less spread (i.e. dense) and the presence of numerous small vessels. The results show that α-shape parameters characterise vascular abnormalities predictive of PDR (AUC 0.73; 95% CI [0.73 0.74]) and have therefore potential to reveal changes in retinal microvascular morphology.

Spotlight on the Disc-Damage Likelihood Scale (DDLS).

The disc damage likelihood scale (DDLS) is a tool for classifying glaucomatous structural changes to the optic disc based on the radial width of the neuroretinal rim at its thinnest location, or if no rim is present, the extent of absence of the rim. Unlike cup disc ratio (CDR), the DDLS also considers disc size. Twenty years after its first description, the aim of this review was to critically appraise evidence for the DDLS and evaluate its role in current practice. A literature search by two independent authors identified 33 relevant articles for inclusion. Five studies evaluated reproducibility, 5 diagnostic performance, and 2 studies examined ability to detect progression. Eleven studies evaluated correlation between DDLS and other markers of glaucoma. Despite the widespread availability of imaging devices such as optical coherence tomography (OCT), clinical examination of the optic disc remains an essential component of glaucoma diagnosis and monitoring. The DDLS provides a reliable method for semi-quantitative clinical grading of the optic disc in glaucoma, with higher reproducibility than methods such as CDR.

Intraocular Pressure Monitoring Using an Intraocular Sensor Before and After Glaucoma Surgery.

PURPOSE: Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, with evidence from landmark randomized controlled trials demonstrating visual field preservation with IOP reduction. Over recent years, the use of remote sensors has formed an increasingly important component of the management of chronic diseases. During the coronavirus disease 2019 pandemic, the ability to remotely monitor IOP proved particularly useful when public stay at home orders have been in place. PATIENTS AND METHODS: This report describes the first case of glaucoma surgery in a patient who had previously received an EYEMATE-IO implant. The EYEMATE-IO is an implant for IOP monitoring placed in the ciliary sulcus during cataract surgery. RESULTS: Remote IOP monitoring enabled the clinician to identify sustained high IOP readings and the need for glaucoma surgery. Postoperatively, response to treatment could be monitored to ensure sufficient long-term IOP control. CONCLUSION: The EYEMATE-IO implanted during cataract surgery in this patient provided valuable remote continuous IOP information that guided timely glaucoma surgical interventions for poorly controlled IOP.

The Assessment of Visual Fields in Infants Using Saccadic Vector Optokinetic Perimetry (SVOP): A Feasibility Study.

Purpose: To examine the feasibility of saccadic vector optokinetic perimetry (SVOP), an automated eye tracking perimeter, as a tool for visual field (VF) assessment in infants. Methods: Thirteen healthy infants aged between 3.5 and 12.0 months were tested binocularly using an adapted SVOP protocol. SVOP uses eye tracking technology to measure gaze responses to stimuli presented on a computer screen. Modifications of SVOP for testing infants included adjusting the fixation target to display a short animation, increasing the stimulus size to equivalent to Goldmann V, and introducing a tiered test pattern strategy. Binocular, single-quadrant confrontation VF testing and Keeler preferential looking cards visual acuity testing was also performed. Results: Using multiple test attempts when required, all but the youngest infant (12 of 13 [92.3%]) successfully completed a 4-point screening test. Seven infants (53.8%) successfully completed the 12-point test, four (30.8%) successfully completed the 20-point test, and three (23.1%) successfully completed the 40-point test. The effect of multiple test attempts and the complexity of the test pattern (number of test points) on performance was investigated, including test completion rate, percentage of correctly seen stimuli, and average time per tested stimulus. Conclusions: The modified SVOP test strategy allowed successful assessment of binocular VFs in healthy infants. Future data collection from larger cohorts of infants is needed to derive normative limits of detection and assess accuracy in detecting and monitoring infant VF abnormalities. Translational Relevance: Eye tracking perimetry may provide a useful method of automated VF assessment in infants.