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Purpose: To compare safety, effectiveness, and baseline predictors of failure in standalone primary Xen45 gel stent (Xen) versus trabeculectomy (Trab) in glaucoma., Design: Retrospective study., Subjects: Subjects that underwent primary Xen or Trab augmented by mitomycin-C with at least 12 months follow-up., Methods: Multinational observational study of eyes in the Fight Glaucoma Blindness international registry MAIN OUTCOME MEASURES: The primary outcome was success at 12 months defined by intraocular pressure (IOP) reduction ≥ 20% from baseline and ≤ threshold IOPs of 15, 18, and 21 mmHg with (qualified) or without (complete) medications and without secondary glaucoma surgery. Multivariable mixed effects Cox regression models were used to identify risk factors for failure in each cohort., Results: A total of 701 eyes (Xen, 308; Trab, 393) of 596 subjects were included with baseline IOP being significantly higher (22.4 vs. 19.9 mmHg, P < 0.001) and baseline medications significantly lower in the Xen versus the Trab group (2.9 vs. 3.4, P < 0.001). Baseline visual field mean deviation was less severe in the Xen group (-9.47 vs. -13.04 dB, P < 0.001). The proportion of complete surgical success was significantly lower in the Xen versus Trab group across the 3 upper IOP limits at 12 months; 32% versus 52% at 15 mmHg, 37% versus 54% at 18 mmHg, and 39% versus 55% at 21 mmHg (P < 0.001). The incidence of postoperative numerical and symptomatic hypotony was lower in the Xen versus Trab group. In the Xen cohort, a higher failure rate was associated with Asian ethnicity (hazard ratio [HR], 1.97; 95% confidence interval (CI), 1.03-3.79) and use of oral acetazolamide at baseline (HR, 1.74; 95% CI, 1.13-2.70), whereas a lower failure rate was associated with diagnosis of ocular hypertension/open-angle glaucoma suspect (HR, 0.40; 95% CI, 0.20-0.82) and secondary open-angle glaucoma (HR, 0.46; 95% CI, 0.26-0.82). Exposure to prostaglandin analog was associated with greater failure in the Trab group (HR, 2.66; 95% CI, 1.18-6.01)., Conclusions: There was significantly greater complete success at 12 months across all complete success definitions for Trab compared with Xen, whereas the rate of postoperative hypotony was significantly lower in the Xen group. Asian ethnicity and use of oral acetazolamide at baseline were associated with greater failure in Xen, whereas exposure to prostaglandin analog was associated with greater failure in Trab patients. Such baseline predictors of success and failure may help guide patient selection for subconjunctival minimally invasive glaucoma surgery in patients undergoing surgical intervention., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the effect of frontloading (multiple) visual field (VF) tests at the same visit for detecting mean deviation (MD) change in slowly progressive glaucoma., Methods: This was a computer simulation study. Baseline MD (range, 0 to -12 dB) and progression rate (range, 0 to -0.4 dB/year, non-inclusive) were generated for 10,000 patients. Each patient had 6 simulated "stable" baseline VF tests. Then follow-up VFs (up to 10 years) were generated by incorporating progression rate and within-visit and between-visit variability. The independent variables were number of VF tests per visit (one non-frontloaded or two frontloaded), VF reliability (100%, 85%, or 70%), repeat testing because of unreliable results (yes or no), and follow-up interval (6-monthly or yearly). The outcomes were detection of progression (MD slope that was negative and significant at p < 0.05), MD at detection, and number of years to detection., Results: Frontloading identified more progressors (62.7%-79.2%) compared with non-frontloading (31.0%-36.7%) at 10 years (p < 0.0001). Six-monthly follow-ups led to greater detection than yearly intervals. Progressors detected by both methods were detected by the non-frontloaded method sooner (up to 0.26 years), but this was small and not clinically significant (MD difference, 0.06 dB). An increase (less severe) in MD, an increase (slower) in progression rate, and an increase in SD of baseline VFs decreased the likelihood of detecting progression., Conclusions: Frontloading VF tests at 6-monthly intervals improve detection rates of MD progression in slowly progressive glaucoma patients compared with performing 1 test per visit at yearly intervals., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Swedish Interactive Thresholding Algorithm (SITA) is the main measurement acquisition algorithm used on the Humphrey Field Analyser, the most commonly used instrument for visual field (VF) assessment worldwide. We compare the sensitivity outputs and reliability parameters of the three currently available SITA algorithms-SITA Standard (SS), Fast (SF), and Faster (SFR), with a focus on the newly released SFR and the 24-2C test grid. SFR displays similar sensitivity outputs to SS and SF, but may not be interchangeable with SS in eyes with more severe VF loss. The reliability metric with the greatest impact on VF reliability is the level of false positives, although the recommended 15 % false positive cut off may be inappropriate as a threshold for judging whether a test is reliable and should be included for use in SFR. Finally, the 24-2C grid may be useful in flagging the presence of a clustered central VF defect, while the 10-2 grid can be used to more comprehensively characterize central field defects. We also discuss strategies to improve testing frequency in clinical practice., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Artificial Intelligence is a rapidly expanding field within computer science that encompasses the emulation of human intelligence by machines. Machine learning and deep learning - two primary data-driven pattern analysis approaches under the umbrella of artificial intelligence - has created considerable interest in the last few decades. The evolution of technology has resulted in a substantial amount of artificial intelligence research on ophthalmic and neurodegenerative disease diagnosis using retinal images. Various artificial intelligence-based techniques have been used for diagnostic purposes, including traditional machine learning, deep learning, and their combinations. Presented here is a review of the literature covering the last 10 years on this topic, discussing the use of artificial intelligence in analysing data from different modalities and their combinations for the diagnosis of glaucoma and neurodegenerative diseases. The performance of published artificial intelligence methods varies due to several factors, yet the results suggest that such methods can potentially facilitate clinical diagnosis. Generally, the accuracy of artificial intelligence-assisted diagnosis ranges from 67-98%, and the area under the sensitivity-specificity curve (AUC) ranges from 0.71-0.98, which outperforms typical human performance of 71.5% accuracy and 0.86 area under the curve. This indicates that artificial intelligence-based tools can provide clinicians with useful information that would assist in providing improved diagnosis. The review suggests that there is room for improvement of existing artificial intelligence-based models using retinal imaging modalities before they are incorporated into clinical practice.

Purpose: To examine the diagnostic accuracy of performing two (frontloaded) versus one (clinical standard) visual field (VF) test per visit for detecting the progression of early glaucoma in data derived from clinical populations., Methods: A computer simulation model was used to follow the VFs of 10,000 glaucoma patients (derived from two cohorts: Heijl et al., Swedish cohort; and Chauhan et al., Canadian Glaucoma Study [CGS]) over a 10-year period to identify patients whose mean deviation (MD) progression was detected. Core data (baseline MD and progression rates) were extracted from two studies in clinical cohorts of glaucoma, which were modulated using SITA-Faster variability characteristics from previous work. Additional variables included follow-up intervals (six-monthly or yearly) and rates of perimetric data loss for any reason (0%, 15% and 30%). The main outcome measures were the proportions of progressors detected., Results: When the Swedish cohort was reviewed six-monthly, the frontloaded strategy detected more progressors compared to the non-frontloaded method up to years 8, 9 and 10 of follow-up for 0%, 15% and 30% data loss conditions. The time required to detect 50% of cases was 1.0-1.5 years less for frontloading compared to non-frontloading. At 4 years, frontloading increased detection by 26.7%, 28.7% and 32.4% for 0%, 15% and 30% data loss conditions, respectively. Where both techniques detected progression, frontloading detected progressors earlier compared to the non-frontloaded strategy (78.5%-81.5% and by 1.0-1.3 years when reviewed six-monthly; 81%-82.9% and by 1.2-2.1 years when reviewed yearly). Accordingly, these patients had less severe MD scores (six-monthly review: 0.63-1.67 dB 'saved'; yearly review: 1.10-2.87 dB). The differences increased with higher rates of data loss. Similar tendencies were noted when applied to the CGS cohort., Conclusions: Frontloaded VFs applied to clinical distributions of MD and progression led to earlier detection of early glaucoma progression., (© 2024 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Clinical Relevance: A method for determining 10-2 deployment in glaucoma with the goal of detecting additional visual field sensitivity for the purpose of functional monitoring is proposed., Background: To provide a pilot method for determining when to deploy the 10-2 visual field (VF) test grid in glaucoma by characterising the 'functional vulnerability zone'., Methods: The cross-sectional 24-2 (central 12 locations) and 10-2 VF results from 133 eyes of 133 glaucoma subjects were used to describe the central Hill of Vision using VF sensitivity. The 'volume' (defined using arbitrary units, A.U.) under the Hill was calculated. A greater A.U. on the 10-2 indicated a functional vulnerability zone (FVZ), signifying additional clinical dynamic range for potential future monitoring. The main outcome measures were calculated A.U. and 24-2 factors which were significantly related to A.U. differences between 24-2 and 10-2., Results: Over 55% of patients had an FVZ (A.U. greater using 10-2). Several 24-2 features (worse mean deviation, worse central 24-2 mean defect, and a higher proportion of defective locations) were significant in the FVZ cohort compared to non-FVZ. 24-2 mean deviation levels at which 10-2 may be favoured were low at -3.16 to -3.62 dB. Specifically, 5 or more defective central 24-2 test locations were associated with an FVZ. Subjects exhibiting a less severe defect on the 10-2 were more likely to have an FVZ, indicating its potential for future VF monitoring., Conclusions: The authors propose several clinical markers, focussing on the 24-2, which can guide clinicians on when the 10-2 may have utility in glaucoma assessment. The authors provide a pilot reference spreadsheet for clinicians to visualise the likelihood of 10-2 utility in the context of an FVZ.

Purpose: To report the outcomes of frontloaded visual field (VF) testing (2 tests per eye on the same visit) over 2 longitudinal, consecutive visits using SITA-Faster (SFR) in terms of global indices, reliability metrics, and test duration., Design: Prospective longitudinal study., Subjects: A total of 902 eyes of 463 subjects with normal, suspect, or manifest glaucoma., Methods: Two intravisit SFR VF tests (T1 and T2) per eye at an initial (T i ) and follow-up (T f ) visit., Main Outcome Measures: Intra- and intervisit global indices, reliability metrics, and test durations., Results: The mean age of the subjects was 63.6 years, and 58.3% were male. Seven hundred ninety eyes (87.4%) had a diagnosis of glaucoma or glaucoma suspicion. The mean duration between visits was 265.0 (standard deviation 98.8) days. In total, 3608 VF tests were analyzed, with the correlation of mean deviation (MD) values of the frontloaded tests at each visit high (T1/T2 MD correlation at initial visit r = 0.83, root mean squared error [RMSE] = 1.26, follow-up visit r = 0.83, RMSE = 1.25, P < 0.0001) and greater than the correlation of MD between visits (T i 1/T f 1 MD correlation r = 0.72, RMSE = 1.31). There was a significant intra-visit decrease in rates of abnormally high sensitivity in the glaucoma hemifield test (3.2% vs. 1.6%, P = 0.0023) and rates of unreliable test results (15.4% vs. 9.2%, P = 0.002) from T1 to T2 in both visits, with a corresponding significant decrease in MD (-1.28 dB vs. -1.68 dB, P < 0.0001) and VF index (P = 0.03). The mean duration of each SFR test was 132.6 (SD 27.2) seconds., Conclusions: Frontloading VFs using SFR produced sets of repeatable perimetric data with significant improvement of reliability indices from the first to second test. This may help increase testing frequency at minimal time cost to meet recommended guidelines and for evaluating patients prone to high variability., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the usefulness of Humphrey Field Analyser (HFA) SITA-Faster 24-2 gaze tracker outputs on interpreting intra-visit visual field (VF) result pairs., Methods: Analysis of 1380 right-left eye pairs and 1432 pairs of test 1-test 2 intrasession VF results of patients seen within a university-based glaucoma service was undertaken to understand gaze deviation distributions. Output gaze tracker results were aggregated into total ticks, sum of amplitudes and average amplitudes. Correlations between visual field indices (mean deviation [MD], "events" and overall hill of vision) and independent variables (age and test order) were performed using one eye from each subject., Results: There was no association of test order (right-left, test 1-test 2) with eye movements. There was a significant, but weak correlation between eye movements and age (r = 0.16). Correlations of eye movements with MD were driven by more severe MD values. There were no significant correlations between intrasession difference in eye movements and the change in MD, number of "events" and hill of vision, or in the root mean square of sensitivity and total deviation values. There was also no significant correlation between gaze tracker outputs and another commonly used "reliability" metric, false positive rate., Conclusions: Eye movement parameters as currently reported by the HFA do not appear to be correlated with key sensitivity parameters when considering the repeatability of intrasession SITA-Faster 24-2 VF results. Thus, current gaze tracker outputs do not appear to provide clinically meaningful information for interpretation of intra-visit visual field results that cannot already be garnered using other strategies., (© 2022 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Clinical Relevance: Frontloaded visual field testing (twice per eye per session) is well-tolerated by patients and technicians, representing a viable strategy that can be implemented in routine clinical practice to capture enough clinical perimetry data for effective disease diagnosis, surveillance and management., Background: To determine the experiences of patients and technicians following the implementation of frontloaded visual field testing (multiple tests per eye within the same session) in a glaucoma service., Methods: This was a retrospective, cross-sectional study. A written questionnaire was administered to patients (three questions) attending the glaucoma service at the Centre for Eye Health for glaucoma assessment and to their administering perimetry technicians (two questions). The questionnaire was administered after static automated perimetry (24-2 SITA-Faster on the Humphrey Field Analyzer) was performed twice for each eye (frontloaded) within the same session. Respondents were asked to provide a 1-5 Likert scale response to questions that targeted operational issues for frontloaded visual field testing. Responses were correlated against to demographic (age, gender, ethnicity) and clinical (diagnosis, refractive error, visual field indices, test duration) parameters., Results: Approximately 90% of patient respondents agreed that frontloaded visual field testing was clearly explained to them, that they were comfortable during the test, and would prefer completing the tests at a single visit rather than returning to repeat the test. Most technician respondents were also able to keep their patients comfortable. 13% of technician respondents felt they ran late during the session, but on average, the total test duration for four visual field tests was 13 minutes, including breaks. There was no correlation found between demographic and clinical factors, and the responses., Conclusions: Frontloaded visual field testing was well-tolerated by patients and technicians. Strategies that may be helpful for other clinics to adopt this new paradigm are described.

Purpose: The purpose of this study was to evaluate the impact of two conventional reliability criteria (false positives [FPs] and seeding point errors [SPEs]) and the concurrent effect of low sensitivity points (≤19 dB) on intrasession SITA-Faster visual field (VF) result correlations., Methods: There were 2320 intrasession SITA-Faster VF results from 1160 eyes of healthy, glaucoma suspects, and subjects with glaucoma that were separated into "both reliable" or "reliable-unreliable" pairs. VF results (mean deviation and pointwise sensitivity) were analyzed against the spectrum of FP rates and SPE, with and without censorship of sensitivity results ≤19 dB. Segmental linear regression was used to identify critical points where visual field results were significantly different between tests due to FP levels., Results: There was a significant, but small (0.09 dB per 1% exceeding 12%) increase in mean deviation, and an increase in the number of points showing a >3 dB sensitivity increase (0.25-0.28 locations per 1% exceeding 12%). SPEs were almost exclusively related to a decrease in sensitivity at the primary seeding points but did not result in significant differences in other indices. Censoring sensitivity results ≤19 dB significantly improved the correlation between reliable and unreliable results., Conclusions: Current criteria for judging an unreliable VF result (FP rate >15% and SPE) can lead to data being erroneously excluded, as many results do not show significant differences compared to those deemed "reliable." Censoring of sensitivity results ≤19 dB improves intrasession correlations in VF results., Translational Relevance: We provide guidelines for assessing the impact of FP, SPE, and low sensitivity results on VF interpretation.

Purpose: To model the healthcare impact (clinical attendance time and financial cost) and clinical outcomes (glaucoma diagnoses) of different risk factor-driven review frequencies for glaucoma suspect patients up until the point of discharge or diagnosis., Methods: Medical records of 494 glaucoma suspects were examined to extract the clinical diagnosis. Two criteria for review periods were defined, based on contrasting stringency from established clinical guidelines: American Academy of Ophthalmology (AAO), more stringent/less frequent; and the Australian National Health and Medical Research Council (NHMRC), less stringent/more frequent. We used these data to model patient outcomes and healthcare costs using a Markov model., Results: The less stringent/more frequent criterion resulted in more high-risk glaucoma suspects requiring more frequent review compared with the more stringent/less frequent criterion. Across the 15 Markov cycles (7.5 years), the less stringent/more frequent review criterion resulted in 6.6% more diagnoses and fewer overall clinical visits (14.7%) and reduced cost per diagnosis by 12% to 32% (P < 0.0001). The number of glaucoma diagnoses made using each criterion converged at 2.5 to 3 years., Conclusions: The stringency of risk assessments for glaucoma suspects impacts review periods and therefore clinical load, healthcare costs, and diagnosis rates. Using current testing methods, more frequent review periods appear advantageous for diagnostic efficiency, with both lower clinic load and lower cost up until the point of discharge or glaucoma diagnosis., Translational Relevance: A less stringent criterion for assessing the risk of developing glaucoma potentially offers a more cost-effective method for reviewing glaucoma suspects, especially within the first 2.5 years.

Purpose: To determine the impact of different numbers of visual field tests per visit for detecting mean deviation changes over time in patients with early glaucoma or suspected glaucoma and to identify a practical approach to maximize change detection., Methods: Intrasession (n = 322) and intersession (n = 323) visual field results for patients with glaucoma or suspected glaucoma were used to model mean deviation change in 10,000 progressing and 10,000 non-progressing computer-simulated patients over time. Variables assessed in the model included follow-up intervals (0.5, 1, or 2 years), reliability rates (70%, 85%, or 100%) and number of visual field tests performed at each visit (one to four)., Results: Two visual field tests per session compared with one provided higher case detection rates at 2 years (99%-99.8% vs. 34.7%-76.3%, respectively), reduced time to detection (three or four visits vs. six to 10, respectively), and more positive mean deviation score (-4 dB vs. -10 dB, respectively) at the point of mean deviation change identification, especially in the context of unreliable results. Performing two tests per visit offered similar advantages compared with more tests. False positive change detection rates (<2.5%), were similar across all conditions. Patients followed up 6 monthly had less severe mean deviation loss at follow-up compared to 1-year and 2-year follow-up intervals., Conclusions: Performing two tests per clinical visit at 6 months is practical using SITA-Faster and provides higher detection rates of mean deviation change in comparison with only one test performed per visit and more spaced-out intervals., Translational Relevance: This model provides guidance for selecting the number of tests per visit to detect mean deviation change.

Objective: Irritable bowel syndrome (IBS) is a chronic disorder associated with an abnormal gastrointestinal microbiome. Microbiome-host interactions are known to influence organ function including in the central nervous system; thus, we sought to identify whether IBS may be a risk factor for the development of glaucoma., Design: Two prospective cohort studies., Subjects: The 1958 United Kingdom Birth Cohort (UKBC; 9091 individuals) and the Danish National Registry of Patients (DNRP; 62,541 individuals with IBS and 625,410 matched general population cohort members)., Methods: In the UKBC, participants were surveyed throughout life (including at ages 42 and 50). The DNRP contains records of hospital-based contacts and prescription data from the national prescription database., Main Outcome Measure: The main outcome measure was incidence of glaucoma. In the UKBC, incident glaucoma at age 50 (n = 48) was determined through comparison of survey responses at ages 42 and 50 years. In the DNRP, glaucoma was assessed by hospital diagnosis (n = 1510), glaucoma surgery (n = 582) and initiation of glaucoma medications (n = 1674)., Results: In the UKBC, the odds ratio (OR) of developing glaucoma between ages 42 and 50 in persons with a chronic IBS diagnosis was increased [OR: 5.84, 95% confidence interval (CI): 2.26-15.13]. People with an IBS diagnosis in the DNRP had a hazard ratio (HR) of 1.35 for developing physician-diagnosed glaucoma (95% CI: 1.16-1.56), an HR of 1.35 for undergoing glaucoma surgery (95% CI: 1.06-1.70) and an HR of 1.19 for initiating glaucoma medication (95% CI: 1.03-1.38)., Conclusions: In two large European cohort studies, IBS is a risk factor for glaucoma., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Purpose: To assess the viability, in terms of time taken for testing and repeatability, of frontloading (performing multiple perimetric examinations) in a single clinic visit., Design: Reliability enhancement analysis., Methods: A total of 329 healthy glaucoma suspect and glaucoma subjects within a glaucoma clinic undergoing perimetric testing using SITA-Faster twice for each eye within the same session were included. Global indices, pointwise sensitivity and probability scores, test duration, and reliability metrics were analysed., Results: For both tests 9.1% of right eye and 6.7% of left eye results were unreliable, with 58.4% and 67.5% of right and left eyes achieving reliable results, respectively; 83.8% of all subjects spent less than 20 minutes performing all tests. Differences in global indices, pointwise sensitivity and probability scores showed no systematic or clinically significant difference between tests one and two for each eye. There was also no systematic difference in the number of test locations identified as defective at the P < .05 level between tests. Test results that were unreliable tended to show more instances of a failed "cluster" criterion that were not repeatable., Conclusions: Frontloading using SITA-Faster was viable for obtaining sets of reliable, repeatable perimetric data in terms of conventional outputs, overcoming practical issues regarding low test reliability using singleton results and confirmation of visual field defects. Despite the need to remain cognisant of the reliability of SITA-Faster, frontloading using this algorithm may be a practical method for meeting recommendations for multiple perimetric data required to make confident inferences about glaucoma state and progression., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the ability of 24-2C and 10-2 test grids in measuring visual field global indices, identifying central visual field defects, and facilitating macular structure-function analysis with OCT scans in glaucoma and glaucoma suspect patients., Design: Prospective, cross-sectional study., Participants: One eye from 131 glaucoma and 57 glaucoma suspect patients recruited from a referral-only, university-based glaucoma clinic., Methods: Each subject underwent perimetric testing using 24-2C SITA-Faster and 10-2 SITA-Fast in random order, and Cirrus OCT macular imaging (Ganglion Cell Analysis) for structure-function correlations., Main Outcome Measures: Visual field global indices (mean deviation, pattern standard deviation, binarized "cluster" pass/fail, and central mean sensitivity), number and proportion of visual field defects, and structure-function concordance with the Cirrus OCT deviation map following visual field location displacement for correspondence with underlying retinal ganglion cell position., Results: Global indices (mean deviation, pattern standard deviation, and central mean sensitivity) were similar between both grids. The 10-2 detected more defects compared with the 24-2C (P < 0.0001 for all patients, P = 0.006 for glaucoma patients). This was preserved when analyzing the proportion of defects in the central visual field for all patients (P = 0.02) but was not significantly different for glaucoma patients (P = 0.051). The 10-2 identified more central "clusters" of 2+ contiguous points of deficit (P < 0.0001). Structure-function comparisons performed at locations where visual field and OCT test locations were colocalized revealed greater concordance of structural and functional deficits using the 10-2 (P < 0.0001). The 10-2 took a median of 201 seconds, and the 24-2C took a median of 154 seconds, corresponding to the different thresholding algorithms., Conclusions: The 24-2C and 10-2 test grids return similar global indices of visual field performance and proportionally similar amounts of central visual field loss. The additional points in the 10-2 grid return more "clusters" of defects and a greater rate of structure-function concordance compared with the 24-2C test grid. Thus, the 24-2C can identify the presence of a clustered central visual field defect using similar probability criteria, whereas the 10-2 may be more useful in comprehensively characterizing the defect and predicting central visual function., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To use factor analysis to visualize and assess the reproducibility and consistency of clinical quantitative parameters that can optimally distinguish among healthy, glaucoma suspect, and manifest glaucoma patients at a cross-sectional level and thus to describe the transition of quantitative change among the diagnostic categories., Design: Retrospective cross-sectional study., Participants: The medical records of healthy, glaucoma suspect, and manifest glaucoma patients (diagnosed by expert clinicians) seen at the Centre for Eye Health in 2015 (n = 148, n = 664, and n = 129, respectively) and 2018 (n = 242, n = 464, and n = 126, respectively) were reviewed. One eye was selected for the study., Methods: Quantitative clinical measures (intraocular pressure [IOP], central corneal thickness [CCT], visual field [VF], and OCT) were extracted and binary logistic (backward stepwise) regression was performed to identify factors that dictated separation between diagnostic pairs. These were used systematically as inputs for factor analysis to determine a final model that could potentially predict a clinical diagnosis., Main Outcome Measures: Intraocular pressure, CCT, VF (mean deviation and pattern standard deviation) indices, and OCT optic nerve head parameters and thickness values (retinal nerve fiber layer [RNFL] and ganglion cell-inner plexiform layer)., Results: Few clinical parameters were identified commonly as significant across all diagnostic pairings for 2015 (3 of 23: IOP, pattern standard deviation, and 7-o'clock RNFL thickness) and 2018 (1 of 23: vertical cup-to-disc ratio). Few parameters overlapped when comparing 2015 and 2018 results, highlighting inconsistencies in the models between years. Factor analysis showed good separation between healthy persons and glaucoma patients. Using biplots to visualize the data in 2-dimensional clusters, glaucoma suspect patients demonstrated substantial overlap with healthy and glaucoma cohorts. The contributions of each parameter to diagnostic separation changed between groups and years., Conclusions: Despite advances in quantitative ocular imaging and perimetry, the transition among healthy, glaucoma suspect, and manifest glaucoma patients remains confounded by a lack of consistent, reproducible combinations of quantitative clinical criteria. These results highlight the nebulousness (at patient-, instrument-, and clinician-related levels) of glaucoma diagnosis that remains contingent on individual clinical expertise and assessment., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop and test the performance of a deep learning-based algorithm for glaucomatous disc identification using monoscopic fundus photographs., Design: Fundus photograph database study., Participants: Four thousand three hundred ninety-four fundus photographs, including 3768 images from previous Sydney-based clinical studies and 626 images from publicly available online RIM-ONE and High-Resolution Fundus (HRF) databases with definitive diagnoses., Methods: We merged all databases except the HRF database, and then partitioned the dataset into a training set (80% of all cases) and a testing set (20% of all cases). We used the HRF images as an additional testing set. We compared the performance of the artificial intelligence (AI) system against a panel of practicing ophthalmologists including glaucoma subspecialists from Australia, New Zealand, Canada, and the United Kingdom., Main Outcome Measures: The sensitivity and specificity of the AI system in detecting glaucomatous optic discs., Results: By using monoscopic fundus photographs, the AI system demonstrated a high accuracy rate in glaucomatous disc identification (92.7%; 95% confidence interval [CI], 91.2%-94.2%), achieving 89.3% sensitivity (95% CI, 86.8%-91.7%) and 97.1% specificity (95% CI, 96.1%-98.1%), with an area under the receiver operating characteristic curve of 0.97 (95% CI, 0.96-0.98). Using the independent online HRF database (30 images), the AI system again accomplished high accuracy, with 86.7% in both sensitivity and specificity (for ophthalmologists, 75.6% sensitivity and 77.8% specificity) and an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.76-1.00)., Conclusions: This study demonstrated that a deep learning-based algorithm can identify glaucomatous discs at high accuracy level using monoscopic fundus images. Given that it is far easier to obtain monoscopic disc images than high-quality stereoscopic images, this study highlights the algorithm's potential application in large population-based disease screening or telemedicine programs., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to characterize the five missense mutations in CYP1B1 gene identified in Pakistani families affected with primary congenital glaucoma (PCG) using various bioinformatics and protein modeling tools., Methods: We previously reported four novel missense mutations in CYP1B1 gene segregating in consanguineous Pakistani families. These mutations were identified by direct sequencing of all coding exons, the exon-intron boundaries and the 5' untranslated region of CYP1B1 using genomic DNA from affected and unaffected family members. In order to understand the effect of CYP1B1 mutations on protein structure and function, we used bioinformatics tools to investigate five mutations including four novels (W434R, D374E, L487P and L177R) and one known (E229K) mutation previously reported by our group in four Pakistani PCG-affected families., Results: In silico analysis of the missense mutations using the computational algorithms SNAP, I-Mutant 2.0 IUPred, PrDOS and PASTA predicted pathogenic effects on stability and function of protein., Conclusion: In silico analysis of identified mutations confirmed their molecular pathogenicity. Similar analysis will be helpful in understanding of the biological role of CYP1B1 and the effect of mutations on the regulatory and enzymatic functions of CYP1B1 that result in PCG.

Monitoring intraocular pressure (IOP) is a critically important part of glaucoma management; however, clinical tonometry predominantly involves sitting postures and is unable to detect variations in response to posture changes, muscular effort, deep respirations and during a wide range of activities, such as playing high wind-resistance instruments and wearing swimming goggles in addition to eye touching and rubbing. For example, the usefulness of 24-hour tonometric phasing may be increased, if nocturnal assessments included side and prone sleeping postures rather than being limited to supine posture tonometry. Continuous monitoring of IOP, which allows unrestricted involvement in a full range of sleep and non-sleep IOP elevating activities would provide an ideal method of quantifying the frequency, duration and degree of episodes of elevation in addition to physiological and pathological circadian rhythmic variations due to treatment. Apart from the degree of exposure to episodes of elevation of IOP, genetic influences and family history of glaucoma, other factors which are or could be associated with increased susceptibility to develop or progress glaucomatous pathology include age, frailty, race, type and degree of refractive error, systemic hypotension and hypertension, vasospasm, migraine, pigmentary dispersion syndrome, pseudoexfoliation syndrome, obstructive sleep apnoea syndrome, diabetes as well as medication interactions and side effects. Such information, when combined with all details relating to episodes of elevation of IOP, appears likely to be a strong basis for the detection, diagnosis and treatment of glaucoma. This review examines the limitations of methods of longitudinal monitoring of IOP with reference to their validity and the varying degrees of invasiveness involved. Also mentioned is the potential value of knowing the frequency, duration and level of variations of optic nerve subarachnoid space pressure, as the interaction of such changes with IOP and their potential influence on the lamina cribrosa, may help determine pathological significance., (© 2016 Optometry Australia.)

Apart from the risk of developing glaucoma there is also the risk that it is not detected and irreversible loss of vision ensues. Some studies of methods of glaucoma diagnosis have examined the results of instrument-based examinations with great if not complete reliance on objective findings in arriving at a diagnosis. The very valuable advances in glaucoma detection instrument technologies, and apparent increasing dependence on them, may have led to reduced consideration of information available from a patient history in those studies. Dependence on objective evidence of glaucomatous pathology may reduce the possibility of detecting glaucoma suspects or patients at risk for becoming glaucoma suspects. A valid positive family history of glaucoma is very valuable information. However, negative family histories can often be unreliable due to large numbers of glaucoma cases being undiagnosed. No evidence of family history is appropriate rather than no family history. In addition the unreliability of a negative family history is increased when patients with glaucoma fail to inform their family members. A finding of no family history can only be stated as no known family history. In examining the potential diagnostic contribution from a patient history, this review considers, age, frailty, race, type and degree of refractive error, systemic hyper- and hypotension, vasospasm, migraine, pigmentary dispersion syndrome, pseudoexfoliation syndrome, obstructive sleep apnea syndrome, diabetes, medication interactions and side effects, the degree of exposure to intraocular and intracranial pressure elevations and fluctuations, smoking, and symptoms in addition to genetics and family history of the disease., (Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The Heidelberg Retina Tomograph (HRT) is a commonly-used clinical instrument for glaucoma diagnosis; however, the repeatability of the two most commonly used analysis tools, Moorfield regression analysis (MRA) and 'glaucoma probability score' (GPS) is not known and could have significant implications for patients at risk or suspected of developing glaucoma. Thus, the intra-visit repeatability of the HRT3 (an objective measure of instrument-induced variability) was investigated in a glaucoma suspect cohort., Methods: Two repeat 15° × 15° optic nerve head scans were taken from 164 eyes of 84 patients using the HRT (HRT3, software version 3) during a single visit. The variability of global and sectoral rim area, rim volume and GPS were analysed with and without image alignment using SPSS 22.0. Repeatability was evaluated as absolute difference between the two measurements., Results: Repeatability of the global rim area, rim volume and GPS were high with and without image registration. Variability increased by a small, yet significant amount without image alignment (p < 0.001 to p = 0.002). This increase was more prominent for sectoral analysis with the exception of the rim area and volume in the temporal sector (p = 0.034 to p < 0.001). Increase in the variability of the GPS was also significant (p < 0.001)., Conclusion: HRT3 demonstrated high short-term repeatability, which significantly improved with image registration for all global measurements. Sectoral analysis demonstrated higher repeatability with image registration for some of the sectors in rim area and volume analysis and all sectors for the GPS. Therefore, depending upon the assessed parameters, image registration may play a significant role in the interpretation of results in glaucoma suspects., (© 2016 Optometry Australia.)

Intraocular pressure may become elevated with muscle exertion, changes in body position and increased respiratory volumes, especially when Valsalva manoeuver mechanisms are involved. All of these factors may be present during physical exercise, especially if hydration levels are increased. This review examines the evidence for intraocular pressure changes during and after physical exercise. Intraocular pressure elevation may result in a reduction in ocular perfusion pressure with the associated possibility of mechanical and/or ischaemic damage to the optic nerve head. A key consideration is the possibility that, rather than being beneficial for patients who are susceptible to glaucomatous pathology, any intraocular pressure elevation could be detrimental. Lower intraocular pressure after exercise may result from its elevation causing accelerated aqueous outflow during exercise. Also examined is the possibility that people who have lower frailty are more likely to exercise as well as less likely to have or develop glaucoma. Consequently, lower prevalence of glaucoma would be expected among people who exercise. The evidence base for this topic is deficient and would be greatly improved by the availability of tonometry assessment during dynamic exercise, more studies which control for hydration levels, and methods for assessing the potential general health benefits of exercise against any possibility of exacerbated glaucomatous pathology for individual patients who are susceptible to such changes., (Copyright © 2015 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.)

This review examines some of the biomechanical consequences associated with the opposing intraocular and intracranial forces. These forces compress the lamina cribrosa and are a potential source of glaucomatous pathology. A difference between them creates a displacement force on the lamina cribrosa. Increasing intraocular pressure and/or decreasing intracranial pressure will increase the trans-lamina cribrosa pressure difference and the risk of its posterior displacement, canal expansion and the formation of pathological cupping. Both intraocular pressure and intracranial pressure can be elevated during a Valsalva manoeuvre with associated increases in both anterior and posterior lamina cribrosa loading as well as its compression. Any resulting thinning of or damage to the lamina cribrosa and/or retinal ganglion cell axons and/or astrocyte and glial cells attached to the matrix of the lamina cribrosa and/or reduction in blood flow to the lamina cribrosa may contribute to glaucomatous neuropathy. Thinning of the lamina cribrosa reduces its stiffness and increases the risk of its posterior displacement. Optic nerve head posterior displacement warrants medical or surgical lowering of intraocular pressure; however, compared to intraocular pressure, the trans-lamina cribrosa pressure difference may be more important in pressure-related pathology of the optic nerve head region. Similarly important could be increased compression loading of the lamina cribrosa. Reducing participation in activities which elevate intraocular and intracranial pressure will decrease lamina cribrosa compression exposure and may contribute to glaucoma management and may have prognostic significance for glaucoma suspects., (© 2016 The Authors. Clinical and Experimental Optometry © 2016 Optometry Australia.)

Intraocular pressure and its fluctuations are associated with the development and progression of glaucoma. This review examines the potential for sleep-related intraocular pressure elevations to contribute to the onset and progression of glaucoma. Also considered is the potential for patient education and appropriate changes in behaviour as a means of reducing exposure to elevated intraocular pressure. A PubMed search using the combination key words 'glaucoma and sleep' was conducted. Information was taken from representative articles from the 187 yielded from the search. Additional papers were found after accessing references in selected papers. Several studies have indicated an association between the progression of glaucoma and both lateral decubitus (side sleep) and supine sleep positions. Evidence that prone sleep positions could raise intraocular pressure to high levels suggests a similar if not stronger association. Intraocular pressure elevation and progression of glaucoma associated with sleep positions suggest that there are similar risks of progression associated with sleep-related body postures adopted during non-sleep activities, such as reading, watching television and sun-bathing. Posture-related management of patients with glaucoma, which is intended to reduce the risk or degree of progression may include the use of specially designed pillows, bed-head elevation and recommendations to avoid postures which induce higher intraocular pressure., (© 2013 The Author. Clinical and Experimental Optometry © 2013 Optometrists Association Australia.)

Background: This study investigated the referral pathways offered to patients with age-related macular degeneration (AMD), diabetic retinopathy (DR) or glaucoma (GL) by ophthalmologists and optometrists., Methods: Australian ophthalmologists and optometrists were surveyed regarding referral decisions to other eye-care specialists (inter- or intra-professional), general medical practitioners (GPs), low vision rehabilitation (LVR) and support services. Thematic analysis and concept mapping were applied to highlight current and ideal referral pathways., Results: The survey was completed by 155 optometrists and 50 ophthalmologists and deemed representative of their respective professions in Australia. Not surprisingly, the vast majority of the participating optometrists (97 to 99 per cent) referred to ophthalmologists regardless of the underlying condition. Clear differences (Chi-square: p < 0.05) were observed in the referral patterns of optometrists and ophthalmologists to GPs and support services. General medical practitioner services were almost exclusively used for patients with DR, while AMD triggered a significantly higher referral rate to low vision rehabilitation and support services than the other two disorders., Conclusion: While ophthalmologists predominantly referred patients with AMD, DR or GL to low vision rehabilitation services, optometrists' referrals were highly skewed toward ophthalmology. Referrals to other supporting services by the two groups were not greatly used. The perceived referral pathways by the two eye-care professionals suggested a unidirectional route, potentially highlighting the need for a more collaborative approach that facilitates optimal use of eye health care and allied services., (© 2013 The Authors. Clinical and Experimental Optometry © 2013 Optometrists Association Australia.)

Background: The aim was to obtain an overview of general medical practitioner (GP) referral pathways to ocular health care and allied services for people identified with age-related macular degeneration (AMD), diabetic retinopathy (DR) or glaucoma (GL)., Methods: A questionnaire was developed to survey GPs in Australia. Questions included demographic information and referral patterns to ocular and health service providers. The survey was posted to 1,050 randomly selected GPs across Australia., Results: Fifty-eight GPs participated in this study amounting to a 6.5 per cent response rate. Nearly all GPs referred patients to ophthalmologists (AMD: 98 per cent; DR: 98 per cent; GL: 95 per cent). A smaller proportion of GPs also referred to low vision rehabilitation (LVR) services (AMD: 34 per cent; DR: 33 per cent; GL: 22 per cent), optometrists (AMD: 26 per cent; DR: 34 per cent; GL: 31 per cent), or support services (AMD: 17 per cent; DR: 40 per cent; GL: 19 per cent). For the three tested conditions, there were no statistically significant differences in the proportions of GPs, who referred to ophthalmologists (p = 0.43), optometrists (p = 0.48) or to low vision rehabilitation services (p = 0.31). The proportion of GPs who referred to support services was significantly higher for patients diagnosed with DR than AMD or GL (p < 0.05)., Conclusion: The majority of GPs referred patients with AMD, DR or GL to ophthalmologists. Fewer GPs considered referrals to optometrists, low vision rehabilitation or support services. General practitioners may need to be more aware about the central role of optometrists in the delivery of primary eye health care. In the interest of optimising eye care, closer working relationships between GPs and optometrists should be fostered., (© 2013 The Authors. Clinical and Experimental Optometry © 2013 Optometrists Association Australia.)

Purpose: To review a range of activities associated with intraocular pressure (IOP) spikes. To examine the possible significance of IOP spikes in conditions such as keratectasia, axial myopia, and glaucoma., Methods: Hypotheses concerning mechanisms for adverse responses to IOP spikes were examined., Results: Apart from the possibility that IOP spikes might cause susceptible corneal, posterior scleral, or optic nerve head tissue to yield to associated distending forces, there is the possibility that these tissues will be also be damaged by increased hydrostatic pressure., Conclusions: In-office tonometry does not indicate the degree to which ocular tissues are exposed to IOP spikes. For eyes that are exposed to IOP spikes of longer duration, that occur frequently and which result in a larger IOP increment, the risk of an adverse response may be greater. Changes in ocular tissues because of increased hydrostatic pressure may include morphological cellular changes and alterations to enzyme function. Eye rubbing may be the most significant mechanism for creating IOP spikes because of the large IOP increments that may be involved, as well as the possibility that abnormal rubbing can become a chronic habit. As appears to be the case in keratoconus, asymmetric exposure to IOP spikes may help to explain some asymmetric presentations of post-laser-assisted in situ keratomileusis, glaucoma, or myopia. Ideally methods for the objective assessment of patient risk for adverse responses to IOP spikes will continue to be developed. A self-administered questionnaire may help identify patients who are significantly exposed to IOP spikes. Family history may indicate an increased risk of diseases for which IOP spikes may have significant implications. Patient counseling regarding the possibility that IOP spiking activities may contribute to the development and/or progression of conditions such as keratectasia, axial myopia, and glaucoma may be indicated.

We recorded pattern electroretinograms, scotopic threshold responses, oscillatory potentials and ganzfeld flash electroretinograms in patients with glaucoma or other optic nerve diseases and in cats with inner retinal damage caused by intravitreal injections of kainic acid. In both studies, the scotopic b-wave and the scotopic threshold responses were normal but the oscillatory potentials and pattern electroretinograms were not. The photopic b-wave was also often reduced in patients with scotopic oscillatory potential reduction, and the reduction was proportionate to the oscillatory potential change. Oscillatory potentials were as frequently reduced as pattern electroretinograms in both patient groups, and in the few cases where only one response was reduced, there was no bias toward either measure. In cats, the effects of intravitreal injection of various doses of kainic acid on the retina were evaluated electrophysiologically, and structural damage was assessed histologically. After 25 nmol of kainic acid, the pattern electroretinograms and oscillatory potentials were reduced but neither the b-waves nor the scotopic threshold responses, were affected. Histologic studies of retinas after this dose showed swollen dendrites that were restricted to the outer part (off-sublamina) of the inner plexiform layer. Serial semithin sections indicated that most, if not all, of the swelling was confined to dendrites of large ganglion cells. Our results indicate that the size and sensitivity of the oscillatory potential response may have a role in the diagnosis and management of early glaucoma and optic nerve disease, and that the photopic electroretinogram may give similar information.