Harvard Glaucoma Fairness: A Retinal Nerve Disease Dataset for Fairness Learning and Fair Identity Normalization

Fairness (also known as equity interchangeably) in machine learning is important for societal well-being, but limited public datasets hinder its progress. Currently, no dedicated public medical datasets with imaging data for fairness learning are available, though minority groups suffer from more health issues. To address this gap, we introduce Harvard Glaucoma Fairness (Harvard-GF), a retinal nerve disease dataset with both 2D and 3D imaging data and balanced racial groups for glaucoma detection. Glaucoma is the leading cause of irreversible blindness globally with Blacks having doubled glaucoma prevalence than other races. We also propose a fair identity normalization (FIN) approach to equalize the feature importance between different identity groups. Our FIN approach is compared with various the-state-of-the-art fairness learning methods with superior performance in the racial, gender, and ethnicity fairness tasks with 2D and 3D imaging data, which demonstrate the utilities of our dataset Harvard-GF for fairness learning. To facilitate fairness comparisons between different models, we propose an equity-scaled performance measure, which can be flexibly used to compare all kinds of performance metrics in the context of fairness. The dataset and code are publicly accessible via \url{https://ophai.hms.harvard.edu/datasets/harvard-glaucoma-fairness-3300-samples/}

Machine learning-derived baseline visual field patterns predict future glaucoma onset in the Ocular Hypertension Treatment Study

PURPOSE: The Ocular Hypertension Treatment Study (OHTS) identified risk factors for primary open-angle glaucoma (POAG) in patients with ocular hypertension, including pattern standard deviation (PSD). Archetypal analysis, an unsupervised machine learning method, may offer a more interpretable approach to risk stratification by identifying patterns in baseline visual fields (VFs). METHODS: There were 3272 eyes available in the OHTS. Archetypal analysis was applied using 24-2 baseline VFs, and model selection was performed with cross-validation. Decomposition coefficients for archetypes (ATs) were calculated. A penalized Cox proportional hazards model was implemented to select discriminative ATs. The AT model was compared to the OHTS model. Associations were identified between ATs with both POAG onset and VF progression, defined by mean deviation change per year. RESULTS: We selected 8494 baseline VFs. Optimal AT count was 19. The highest prevalence ATs were AT9, AT11, and AT7. The AT-based prediction model had a C-index of 0.75 for POAG onset. Multivariable models demonstrated that a one-interquartile range increase in the AT5 (hazard ratio [HR] = 1.14; 95% confidence interval [CI], 1.04-1.25), AT8 (HR = 1.22; 95% CI, 1.09-1.37), AT15 (HR = 1.26; 95% CI, 1.12-1.41), and AT17 (HR = 1.17; 95% CI, 1.03-1.31) coefficients conferred increased risk of POAG onset. AT5, AT10, and AT14 were significantly associated with rapid VF progression. In a subgroup analysis by high-risk ATs (\u3e95th percentile or \u3c75th percentile coefficients), PSD lost significance as a predictor of POAG in the low-risk group. CONCLUSIONS: Baseline VFs, prior to detectable glaucomatous damage, contain occult patterns representing early changes that may increase the risk of POAG onset and VF progression in patients with ocular hypertension. The relationship between PSD and POAG is modified by the presence of high-risk patterns at baseline. An AT-based prediction model for POAG may provide more interpretable glaucoma-specific information in a clinical setting

Deep Ocular Phenotyping Across Primary Open-Angle Glaucoma Genetic Burden

IMPORTANCE: Better understanding of primary open-angle glaucoma (POAG) genetics could enable timely screening and promote individualized disease risk prognostication. OBJECTIVE: To evaluate phenotypic features across genetic burden for POAG. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional, population-based study conducted from 2006 to 2010. Included participants were individuals from the UK Biobank aged 40 to 69 years. Individuals with non-POAG forms of glaucoma were excluded from the analysis. Data were statistically analyzed from October 2022 to January 2023. MAIN OUTCOMES AND MEASURES: POAG prevalence based on structural coding, self-reports, and glaucoma-related traits. RESULTS: Among 407 667 participants (mean [SD] age, 56.3 [8.1] years; 219 183 majority sex [53.8%]) were 14 171 POAG cases. Area under receiver operating characteristic curve for POAG detection was 0.748 in a model including polygenic risk score (PRS), age, sex, and ancestry. POAG prevalence in the highest decile of PRS was 7.4% (3005 of 40 644) vs 1.3% (544 of 40 795) in lowest decile (P < .001). A 1-SD increase in PRS was associated with 1.74 times higher odds of POAG (95% CI, 1.71-1.77), a 0.61-mm Hg increase in corneal-compensated intraocular pressure (IOP; 95% CI, 0.59-0.64), a -0.09-mm Hg decrease in corneal hysteresis (95% CI, -0.10 to -0.08), a 0.08-mm Hg increase in corneal resistance factor (95% CI, 0.06-0.09), and a -0.08-diopter decrease in spherical equivalent (95% CI, -0.11 to -0.07; P < .001 for all). A 1-SD increase in PRS was associated with a thinning of the macula-region retinal nerve fiber layer (mRNFL) of 0.14 μm and macular ganglion cell complex (GCC) of 0.26 μm (P < .001 for both). In the subset of individuals with fundus photographs, a 1-SD increase in PRS was associated with 1.42 times higher odds of suspicious optic disc features (95% CI, 1.19-1.69) and a 0.013 increase in cup-disc ratio (CDR; 95% CI, 0.012-0.014; P < .001 for both). A total of 22 of 5193 fundus photographs (0.4%) in decile 10 had disc hemorrhages, and 27 of 5257 (0.5%) had suspicious optic disc features compared with 9 of 5158 (0.2%) and 10 of 5219 (0.2%), respectively, in decile 1 (P < .001 for both). CDR in decile 10 was 0.46 compared with 0.41 in decile 1 (P < .001). CONCLUSION AND RELEVANCE: Results suggest that PRS identified a group of individuals at substantially higher risk for POAG. Higher genetic risk was associated with more advanced disease, namely higher CDR and corneal-compensated IOP, thinner mRNFL, and thinner GCC. Associations with POAG PRS and corneal hysteresis and greater prevalence of disc hemorrhages were identified. These results suggest that genetic risk is an increasingly important parameter for risk stratification to consider in clinical practice

Comparing The Impact Of Refractive And Nonrefractive Vision Loss On Disability: The Salisbury Eye Evaluation

Purpose: To compare the effects of uncorrected refractive error (URE) and nonrefractive visual impairment (VI) on disability measures. Design: Cross-sectional population-based study. Participants: 2469 individuals with binocular presenting visual acuity (PVA) of 20/80 or better who participated in the first round of the Salisbury Eye Evaluation study. Methods: URE was defined as binocular PVA of 20/30 or worse, improving to better than 20/30 with subjective refraction. VI was defined as post-refraction binocular best corrected visual acuity (BCVA) of 20/30 or worse. The visual acuity decrement attributable to VI was calculated as the difference between BCVA and 20/30 while that due to URE was taken as the difference between PVA and BCVA. Multivariable regression analyses were used to assess the disability impact of 1) vision status using the group with normal vision as reference and 2) one-line decrement in acuity due to VI and URE. Main Outcome Measures: Objective measures of visual function obtained from timed performance of mobility and near vision tasks, self-reported driving cessation, and self reported visual disability measured by the Activities of Daily Vision (ADV) scale. Results: Compared to individuals with normal vision, subjects with VI (n=191) demonstrated a significant decline in all objective and subjective metrics of visual function (p\u3c0.05) while subjects with URE (n=132) demonstrated slower walking speeds, slower near task performance, more frequent driving cessation, and lower ADV scores, but did not demonstrate slower stair climbing or descent speed. For all disability metrics evaluated, the impact of VI was greater than the impact of URE. The impact of a one-line decrement in visual acuity due to VI was associated with greater deficits in mobility measures, driving cessation, and self-reported visual function when compared to a one-line visual acuity decrement due to URE. Conclusions: VI is associated with greater disability than URE across a wide variety of functional measures, even in analyses adjusting for the severity of vision loss. Refractive and non-refractive vision loss should be distinguished in studies evaluating visual disability, and should be understood to have differing consequences

Interaction of background genetic risk, psychotropic medications, and primary angle closure glaucoma in the UK Biobank.

Background/aimsPsychotropic medications have been reported as a risk factor for angle closure disease. However, the interaction between background genetic risk for primary angle closure glaucoma (PACG) and susceptibility to angle closure disease among psychotropic medication users has not been investigated. Here we demonstrate the utility of a genome-wide polygenic risk score (PRS) in identifying and risk-stratifying subjects with PACG and investigate the association between PACG genetic burden and exposure to psychotropic medications on prevalent angle closure.MethodsThis analysis used the UK Biobank dataset, a prospective cohort study of 502,506 UK residents. We constructed a PACG PRS for participants using genome-wide association study summary statistics from a multiethnic meta-analysis using the Lassosum method.ResultsAmong the 441,054 participants, 959 (0.22%) were identified as PACG cases. Individuals with PACG had higher PRS compared to those without PACG (0.24±1.03 SD vs. 0.00±1.00 SD, pConclusionWe demonstrate the utility of a PRS for identifying individuals at higher risk of PACG. Additionally, we demonstrate an important relationship where the association between psychotropic medications use and PACG diagnosis varies across the polygenic risk spectrum

The Effectiveness of Intracameral Moxifloxacin Endophthalmitis Prophylaxis for Trabeculectomy

To analyze the effectiveness of intracameral moxifloxacin prophylaxis in reducing acute postoperative endophthalmitis after trabeculectomy and combined trabeculectomy plus cataract extraction. Retrospective clinical registry analysis. Patients undergoing either trabeculectomy or trabeculectomy plus cataract extraction at Aravind Eye Hospitals (AEH) between 2009 and 2018 (inclusive). Electronic health records data were analyzed before and after implementation of routine intracameral moxifloxacin, and acute postoperative endophthalmitis rates were compared. During 2015, routine intracameral moxifloxacin prophylaxis was added in a step-wise fashion throughout AEH. Date of implementation was used to create group 1 (without intracameral moxifloxacin prophylaxis) and group 2 (with intracameral moxifloxacin prophylaxis). The primary outcome was the difference in acute (≤6 weeks) postoperative endophthalmitis between groups 1 and 2. Review of culture results, visual acuity, and intraocular pressure also was performed for patients with endophthalmitis. Thirty-eight thousand nine hundred eyes (group 1) did not receive intracameral moxifloxacin, whereas 19 086 eyes (group 2) did. Although the rate of noninfectious postoperative complications was not significantly different (0.81% vs. 0.67%; P = 0.07), a significantly lower rate of acute postoperative endophthalmitis was found in group 2 versus group 1 (0.03% vs. 0.08%; P = 0.03). Patients receiving intracameral moxifloxacin showed approximately 2.5-times lower odds of infection (odds ratio, 0.39 for group 2 vs. group 1; 95% confidence interval, 0.16–0.95) and almost 4-times lower odds after adjustment for covariates (odds ratio, 0.26 for group 2 vs. group 1; 95% confidence interval, 0.09–0.74). The rate of early postoperative infection after intracameral moxifloxacin introduction was lower for patients undergoing both trabeculectomy alone (0.09%–0.03%; P = 0.27) and combined trabeculectomy plus cataract extraction (0.08%–0.03%; P = 0.06). Although most cultures yielded no growth, no Staphylococcus or gram-negative growth was found for patients in group 2, who received intracameral moxifloxacin. Intracameral moxifloxacin prophylaxis was associated with a nearly 4-fold lower rate of early postoperative endophthalmitis in patients undergoing trabeculectomy or combined trabeculectomy plus cataract extraction

Response of patients with refractory myasthenia gravis to rituximab: a retrospective study

Introduction: Myasthenia gravis, an autoimmune disorder of neuromuscular transmission, is treated by an array of immunomodulating therapies. A variable response is observed with certain patients being medically refractory. Methods: We report the results of 14 refractory generalized myasthenia gravis patients (6 AChR+; 8 MuSK+) treated with rituximab. Results: Sustained clinical improvement was observed in all patients as well as a reduction of conventional immunotherapies. Prednisone dose decreased a mean of 65.1%, 85.7%, and 93.8% after cycle 1, 2, and 3 of rituximab therapy, respectively. A statistically significant reduction in plasma exchange sessions was seen after cycle 1 with all patients being off of plasma exchange after cycle 3. Acetylcholine receptor antibody titers decreased a mean of 52.1% (p = 0.0046) post-cycle 2. Conclusion: Our results support the hypothesis that rituximab is beneficial and well tolerated in managing refractory myasthenia gravis and nearly doubles published cases. We propose that B-cell-directed therapies may become an attractive option and suggest pursuit of a prospective trial

TIE1 and TEK signalling, intraocular pressure, and primary open-angle glaucoma: a Mendelian randomization study

Acknowledgements: Not applicable.Background: In primary open-angle glaucoma (POAG), lowering intraocular pressure (IOP) is the only proven way of slowing vision loss. Schlemm’s canal (SC) is a hybrid vascular and lymphatic vessel that mediates aqueous humour drainage from the anterior ocular chamber. Animal studies support the importance of SC endothelial angiopoietin-TEK signalling, and more recently TIE1 signalling, in maintaining normal IOP. However, human genetic support for a causal role of TIE1 and TEK signalling in lowering IOP is currently lacking. Methods: GWAS summary statistics were obtained for plasma soluble TIE1 (sTIE1) protein levels (N = 35,559), soluble TEK (sTEK) protein levels (N = 35,559), IOP (N = 139,555) and POAG (Ncases = 16,677, Ncontrols = 199,580). Mendelian randomization (MR) was performed to estimate the association of genetically proxied TIE1 and TEK protein levels with IOP and POAG liability. Where significant MR estimates were obtained, genetic colocalization was performed to assess the probability of a shared causal variant (PPshared) versus distinct (PPdistinct) causal variants underlying TIE1/TEK signalling and the outcome. Publicly available single-nucleus RNA-sequencing data were leveraged to investigate differential expression of TIE1 and TEK in the human ocular anterior segment. Results: Increased genetically proxied TIE1 signalling and TEK signalling associated with a reduction in IOP (− 0.21 mmHg per SD increase in sTIE1, 95% CI = − 0.09 to − 0.33 mmHg, P = 6.57 × 10–4, and − 0.14 mmHg per SD decrease in sTEK, 95% CI = − 0.03 to − 0.25 mmHg, P = 0.011), but not with POAG liability. Colocalization analysis found that the probability of a shared causal variant was greater for TIE1 and IOP than for TEK and IOP (PPshared/(PPdistinct + PPshared) = 0.98 for TIE1 and 0.30 for TEK). In the anterior segment, TIE1 and TEK were preferentially expressed in SC, lymphatic, and vascular endothelium. Conclusions: This study provides novel human genetic support for a causal role of both TIE1 and TEK signalling in regulating IOP. Here, combined evidence from cis-MR and colocalization analyses provide stronger support for TIE1 than TEK as a potential IOP-lowering therapeutic target

Innovation Competence of the Mathematics Teacher

У статті проаналізовано погляди вітчизняних та зарубіжних науковців на поняття «інноваційна компетентність учителя»; визначено поняття «інноваційна компетентність учителя математики» як складову загальної професійної компетентності та необхідну умову формування математичної компетентності, зміст якої зумовлюється особливостями інноваційної діяльності, її суспільною значимістю, творчим характером та спрямованістю на неперервне творення нового, розвиток особистісного й професійного потенціалу педагога; виділено концептуальні положення щодо аналізу структури та змісту цього поняття; виокремлено компоненти інноваційної компетентності вчителя математики та запропоновано напрями її набуття у процесі викладання дисциплін математичного циклу.The article analyzes the views of native and foreign scientists on the concept «innovation competence of the teacher», the concept «innovation competence of the mathematics teacher» is defined, the conceptual provisions concerning the analysis of the structure and content of this concept are described, the components of the innovation competence of the mathematics teacher are outlined and the directions of their formation in the teaching disciplines of mathematical cycle are proposed. The formation of future teachers of mathematics readiness to innovative pedagogical activity is an objective process of purposeful preparation for the creation, implementation and dissemination of educational innovations, which is based on: 1) the adaptation of students to higher education, the implementation of the principle of continuity between the older and the higher school, the formation of motivation of the students for professional activities; 2) maximum use of innovative techniques in the study of the disciplines of mathematical cycle, giving the educational process of students the creative, innovative character; 3) deepening integration of psycho-pedagogical and professional knowledge of future teachers of mathematics; application of innovative information technologies in the educational process; 4) the use of the system principle of training of future specialists in the design, development and partial validation of models of mathematics teacher’s work in the form of a common scheme or plan activities in the implementation of the educational process, based on the predominant activity of students, organized and created by the teacher; 5) the development and application of «prognostic acmeological training» of future teachers of mathematics to innovative pedagogical activity. The predictability of this preparation means its orientation to the school of the future taking into account the main trends in the development of technologies for teaching mathematics. Its implementation on a contextual basis provides a consistent use of all types of preparation of future teachers of mathematics. The innovative competence of teachers of mathematics is seen as part of general professional competence and the necessary condition for the formation of mathematical competence, the content of which is determined by the peculiarities of innovative activity, its social significance, creative nature and focus on continuous creation of something new, development of personal and professional potential of the teacher