Gap Analysis of Glaucoma Examination Concept Representations within Standard SNOMED Clinical Terms.

PURPOSE: Standardization of eye care data is important for clinical interoperability and research . We aimed to address gaps in the representations of glaucoma examination concepts within Systemized Nomenclature of Medicine - Clinical Terms (SNOMED-CT), the preferred terminology of the American Academy of Ophthalmology. DESIGN: Study of data elements. METHODS: Structured eye exam data fields from two electronic health records (EHR) systems (Epic Systems and Medisoft) were compared against existing SNOMED-CT codes for concepts representing glaucoma examination findings3. Glaucoma specialists from multiple institutions were surveyed to identify high-priority gaps in representation, which were discussed among the SNOMED International Eye Care Clinical Reference Group. Proposals for new codes to address the gaps were formulated and submitted for inclusion in SNOMED-CT. MAIN OUTCOME MEASURES: Gaps in SNOMED-CT glaucoma examination concept representations RESULTS: We identified several gaps in SNOMED-CT regarding glaucoma examination concepts. A survey of glaucoma specialists identified high-priority data elements within the categories of tonometry and gonioscopy. For tonometry, there was consensus that we need to define new codes related to maximum intraocular pressure (IOP) and target IOP, and to delineate all methods of measuring IOP. These new codes were proposed and successfully added to SNOMED-CT for future use. Regarding gonioscopy, the current terminology did not include the ability to denote the gonioscopic grading system used (e.g., Shaffer or Spaeth), degree of angle pigmentation, iris configuration (except for plateau iris), and iris approach. There was also no ability to specify eye laterality or angle quadrant for gonioscopic findings. We proposed a framework for representing gonioscopic findings as observable entities in SNOMED-CT. DISCUSSION: There are existing gaps in the standardized representation of findings related to tonometry and gonioscopy within SNOMED-CT. These are important areas for evaluating clinical outcomes and enabling secondary use of EHR data for glaucoma research. This international, multi-institutional collaborative process enabled identification of gaps, prioritization, and development of data standards to address these gaps. CONCLUSION: Addressing these gaps and augmenting SNOMED-CT coverage of glaucoma examination findings could enhance clinical documentation and future research efforts related to glaucoma.

Screening of Glaucoma: Consensus and Directions.

PURPOSE: Glaucoma is a leading public health concern globally. This summary discusses barriers to glaucoma screening and novel strategies for a cost-effective glaucoma screening. METHODS/RESULTS: We discuss barriers to glaucoma screening and recent advancements in glaucoma detection and care, including targeted screening approach as well as telemedicine, genetic testing, and artificial intelligence (AI). A major barrier to glaucoma screening is the cost-effectiveness of case finding resulting from the low prevalence of the disease and the complexity of the diagnosis. Targeted-screening, as well as multi-level screening, can reduce the false positive rate and increase the cost-effectiveness of the program. Telemedicine, availability of genetic testing and polygenic risk scores, and AI provide the opportunity for novel glaucoma screening programs in primary care, portable, and home-based settings and will be helpful for lowering the costs, identifying patients in need of urgent treatment and enabling timely diagnosis and early intervention. CONCLUSIONS: Screening of glaucoma is challenging and changing. Recent advancements in digital technology and genetics have led to the development of tools that are promising for novel screening methodologies. Clinical trials are needed to demonstrate the long-term effect of targeted screening on the burden of glaucoma worldwide.

Suspicious eyes - Elvis's glaucoma battle.

Elvis Presley (1935-1977) is an iconic figure in modern pop culture. Although many of his medical conditions have been the subject of extensive speculation, less is known about his ophthalmological problems, including steroid-induced glaucoma caused by a life-long use of steroids, both prescribed and self-administered, and secondary angle closure glaucoma most likely due to anterior uveitis. Further, he had an episode of acute angle closure glaucoma in 1971 that was treated with a subconjunctival injection of a mydriatic agent or, less likely, a paracentesis combined with an iridotomy. David Meyer, MD, was Presley's main ophthalmologist from 1971 until the latter's death in 1977.

Detection of glaucoma progression on longitudinal series of en-face macular optical coherence tomography angiography images with a deep learning model.

BACKGROUND/AIMS: To design a deep learning (DL) model for the detection of glaucoma progression with a longitudinal series of macular optical coherence tomography angiography (OCTA) images. METHODS: 202 eyes of 134 patients with open-angle glaucoma with ≥4 OCTA visits were followed for an average of 3.5 years. Glaucoma progression was defined as having a statistically significant negative 24-2 visual field (VF) mean deviation (MD) rate. The baseline and final macular OCTA images were aligned according to centre of fovea avascular zone automatically, by checking the highest value of correlation between the two images. A customised convolutional neural network (CNN) was designed for classification. A comparison of the CNN to logistic regression model for whole image vessel density (wiVD) loss on detection of glaucoma progression was performed. The performance of the model was defined based on the confusion matrix of the validation dataset and the area under receiver operating characteristics (AUC). RESULTS: The average (95% CI) baseline VF MD was -3.4 (-4.1 to -2.7) dB. 28 (14%) eyes demonstrated glaucoma progression. The AUC (95% CI) of the DL model for the detection of glaucoma progression was 0.81 (0.59 to 0.93). The sensitivity, specificity and accuracy (95% CI) of DL model were 67% (34% to 78%), 83% (42% to 97%) and 80% (52% to 95%), respectively. The AUC (95% CI) for the detection of glaucoma progression based on the logistic regression model was lower than the DL model (0.69 (0.50 to 0.88)). CONCLUSION: The optimised DL model detected glaucoma progression based on longitudinal macular OCTA images showed good performance. With external validation, it could enhance detection of glaucoma progression. TRIAL REGISTRATION NUMBER: NCT00221897.

Assessment of Missing Data on Glaucoma Severity among Participants in the NIH All of Us Research Program of the United States.

PRECIS: There were statistically significant differences across multiple socioeconomic characteristics and self-reported barriers to care among primary glaucoma patients with severity staging data versus those missing this data in the NIH All of Us database. PURPOSE: To characterize missing data among glaucoma patients within All of Us. PATIENTS AND METHODS: We used diagnosis codes to define cohorts of primary glaucoma patients with and without severity staging specified. Descriptive analyses were conducted by presence of disease severity stage. Analysis of missing data was conducted using a set intersection plot and Little's Test of Missing Completely at Random. T-tests were performed to evaluate differences. RESULTS: Of 2982 participants, 1714 (57%) did not have glaucoma severity stage specified, and 11 of 23 analyzed variables had missing data. Little's Test indicated data was not missing completely at random (P<0.001). Significant differences existed between the two cohorts with respect to age, age of first glaucoma diagnosis, gender, ethnicity, education, income, insurance, history of glaucoma surgery and medication use, and answers regarding ability to afford eyeglasses and having seen an eye care provider in the last 12 months (all P values≤0.01). CONCLUSION: There were significant differences between glaucoma participants with glaucoma severity stage specified versus those with unstaged disease across multiple socioeconomic characteristics and self-reported barriers to care. Glaucoma severity staging data was not missing completely at random. The unstaged cohort included higher rates of multiple underrepresented communities, which may potentially contribute to bias in ophthalmology research as participants from vulnerable populations may be disproportionately excluded from electronic health records or claims data studies where diagnosis codes with severity/staging levels are used to examine risk factors for disease, progression, and treatment efficacy.

Relationship between Retinal Oxygen Saturation and the Severity of Visual Field Damage in Glaucoma.

PRCIS: Increased oxygen saturation was significantly associated with the severity of VF damage in glaucoma patients. PURPOSE: To investigate the association between retinal oxygen saturation (StO2) % and the severity of visual field (VF) loss in glaucoma. METHODS: A total of 198 eyes from 131 glaucoma patients were included in this cross-sectional study. Participants underwent imaging using ocular oximetry (Zilia; Quebec City, Canada) and 24-2 SITA standard VF (Carl Zeiss-Meditec, San Leandro). StO2 (%), was measured at 2 locations of the peripapillary optic nerve head (ONH) (superotemporal, and inferotemporal). Measurements were reported as the mean of at least 5 measurements in each location. Associations between the severity of VF loss, reported as mean deviation (MD), and StO2 (%) was calculated. RESULTS: 198 eyes of 131 patients (mean (95% CI) age, 71.1 (68.9,73.3) years, 68 females [51.9%], 63 males (48.1%)) were analyzed. In univariable analysis, higher StO2 -0.06 (-0.12, 0.00) was associated with severity in all hemifields (P=0.047). Multivariate regression analysis showed that each 1% increase in StO2 was associated with -0.06 (-0.12,-0.00) dB loss in MD in all hemifields (P=0.043). In multivariate regression analysis in the superior hemifields, higher StO2 -0.07 (-0.16, 0.01) tended to be associated with superior hemifield severity (P=0.09). CONCLUSIONS: Retinal oximetry enabled the continuous quantitative measurement of retinal StO2. Increased StO2 was significantly associated with the severity of VF damage in glaucoma patients.

Time to glaucoma progression detection by optical coherence tomography and visual field in glaucoma individuals of African descent.

PURPOSE: To examine the time to glaucoma progression detection by retinal nerve fiber layer thickness (RNFLT) and visual field (VF) among African descent (AD) individuals. DESIGN: Retrospective cohort study. METHODS: Setting: Multi-center. STUDY POPULATION: We included AD glaucoma eyes from DIGS/ADAGES with ≥2-year/5-visits of optic nerve head RNFLT and 24-2 VF examinations. Intervention or Observation Procedure: Rates of VF mean deviation (MD) and RNFLT worsening were analyzed using linear mixed-effects models, and longitudinal data was simulated using the variability estimates. MAIN OUTCOME MEASURE: The simulated time to detect trend-based glaucoma progression was assessed with assumed rates of VF MD and RNFLT change derived from the cohort (25th, 50th, 75th percentile [p25, median, p75] slopes and mean slopes). Severity-stratified analyses were also performed. RESULTS: We included 184 eyes from 128 AD subjects (mean baseline age: 63.4 years; VF MD: -4.2 dB, RNFLT: 80.2 µm). The p25, median, mean and p75 rates of change were -0.43, -1.01, -1.15 and -1.64 µm/year for RNFLT, and 0.00, -0.21, -0.30 and -0.51 dB/year for VF MD, respectively. Compared to VF MD, RNFLT showed an overall shorter mean time to progression detection (time difference: 0.4-1.7 years), with the mean rates showing the largest difference (RNFLT: 5.2 years vs. VF MD: 6.9 years). Similarly, we found an overall shorter time to detect RNFLT progression, compared to that of VF MD progression, in mild glaucoma eyes (≥1 year earlier) and in moderate-advanced glaucoma eyes (∼0.5 year earlier). CONCLUSIONS: Computer simulation showed potentially shorter time to detect RNFLT progression than VF MD progression in AD eyes. Our findings support the importance of using RNFLT to detect progressive glaucoma in AD individuals.

Wide-Field Optical Coherence Tomography Imaging Improves Rate of Change Detection in Progressing Glaucomatous Eyes Compared With Standard-Field Imaging.

Purpose: To compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images. Methods: Forty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0 dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included. Results: Thirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27). Conclusions: In this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high myopia.

Social Factors Associated with the Risk of Glaucoma Suspect Conversion to Glaucoma: Analysis of the Nationwide All of Us Program.

PURPOSE: To examine social factors associated with the 5-year risk of glaucoma suspects (GS) converting to open-angle glaucoma (OAG). DESIGN: Retrospective cohort analysis. SUBJECTS: We screened for participants diagnosed with GS in the All of Us database. Cases that converted to OAG within 5 years of GS diagnosis (the "conversion group") were compared with control cases that did not convert. METHODS: Demographic, socioeconomic and health-care utilization data of the cases were extracted and compared between the conversion group and the control group. Multivariable Cox proportional hazards modeling was used to identify potential factors associated with the risk of conversion. MAIN OUTCOME MEASURES: Hazard ratios (HRs) of significant factors associated with the risk of conversion. RESULTS: A total of 5274 GS participants were identified, and 786 (15%) cases converted to OAG within 5-year follow-up. The 2 groups showed significant differences in age, race, gender, employment status, income/education level, history of intraocular surgery, and health-care utilization patterns. In the multivariable model, African American/Black race (HR : 1.70 [95% confidence interval (CI) 1.44-2.00]), older age at GS diagnosis (1.17 [95% CI 1.09-1.25]), male gender (1.30 [95% CI 1.13-1.50], no history of recreational drug use (1.23 [1.07-1.42]), history of intraocular surgery (1.60 [95% CI 1.02-1.53]), and having more reasons for delayed health-care access (2.27 [95% CI 1.23-4.18]) were associated with a greater hazard of conversion, while being employed (0.71 [95% CI 0.60-0.86]) was associated with a smaller hazard of conversion (P < 0.05 for all). CONCLUSIONS: Several social factors were associated with the conversion from GS to OAG, which may help to identify patients at higher risk of disease progression. Future studies are needed to examine the basis for these findings and the potential interventions that could address them. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Rates of Choriocapillaris Microvascular Dropout and Macular Structural Changes in Glaucomatous Optic Neuropathy With and Without Myopia.

PURPOSE: To evaluate the association between rates of juxtapapillary choriocapillaris microvasculature dropout (MvD) change and rates of ganglion cell inner plexiform layer (GCIPL) loss in primary open-angle glaucoma (POAG) and glaucoma suspect eyes with and without myopia. DESIGN: Cohort study from clinical trial data. METHODS: 238 eyes from 155 POAG and glaucoma suspect patients were stratified into no-myopia (axial length (AL) ≤ 24 mm; n = 78 eyes), mild myopia (24 mm < AL ≤ 26 mm; n = 114 eyes), and high myopia (AL > 26 mm; n = 46 eyes). Eyes with a minimum of 3 visits and 1.5 years of follow-up with both optical coherence tomography angiography (OCT-A) and OCT macula scans were included. Presence, area, and angular circumference of juxtapapillary MvD were evaluated on en face choroidal images and horizontal B-scans obtained from OCT-A imaging. RESULTS: Over the mean follow-up of 4.4 years, the mean MvD area rates of change (95% CI) were largest in high and mild myopia group (0.04 [0.03, 0.05] mm2/year in both groups), followed by the no-myopia group (0.03 [0.02, 0.04] mm2/year). The mean MvD angular circumference rates of change (95% CI) were highest in mild myopia group (8.7° [6.9°, 10.5°]/year) followed by the high myopia and no-myopia groups (8.1° [5.3°, 10.9°]/year, and 7.4° [5.3°, 9.6°]/year, respectively). While the mean global GCIPL thinning rates between eyes with MvD at baseline compared to eyes without were similar in all myopia groups, the rates of MvD area change were significantly faster in all myopia groups with baseline MvD (all p ≤ 0.004). Significant faster rates of MvD angular circumference change were found in the mild myopia group with baseline MvD (P < .001) only. In multivariable models, the rates of GCIPL thinning over time were significantly associated with rates of MvD angular circumference change and MvD area change (R2 = 0.33, P < .001 and R2 = 0.32, P = .006, respectively). CONCLUSIONS: Rates of GCIPL thinning were associated with rates of MvD area and angular circumference change over time in myopic POAG eyes. Utilizing OCT-A to detect MvD may provide an additional tool for monitoring macular structural changes in glaucomatous eyes with myopia.

Administration of Bicarbonate Protects Mitochondria, Rescues Retinal Ganglion Cells, and Ameliorates Visual Dysfunction Caused by Oxidative Stress.

Oxidative stress is a key factor causing mitochondrial dysfunction and retinal ganglion cell (RGC) death in glaucomatous neurodegeneration. The cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway is involved in mitochondrial protection, promoting RGC survival. Soluble adenylyl cyclase (sAC) is a key regulator of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, which is known to protect mitochondria and promote RGC survival. However, the precise molecular mechanisms connecting the sAC-mediated signaling pathway with mitochondrial protection in RGCs against oxidative stress are not well characterized. Here, we demonstrate that sAC plays a critical role in protecting RGC mitochondria from oxidative stress. Using mouse models of oxidative stress induced by ischemic injury and paraquat administration, we found that administration of bicarbonate, as an activator of sAC, protected RGCs, blocked AMP-activated protein kinase activation, inhibited glial activation, and improved visual function. Moreover, we found that this is the result of preserving mitochondrial dynamics (fusion and fission), promoting mitochondrial bioenergetics and biogenesis, and preventing metabolic stress and apoptotic cell death. Notably, the administration of bicarbonate ameliorated mitochondrial dysfunction in RGCs by enhancing mitochondrial biogenesis, preserving mitochondrial structure, and increasing ATP production in oxidatively stressed RGCs. These findings suggest that activating sAC enhances the mitochondrial structure and function in RGCs to counter oxidative stress, consequently promoting RGC protection. We propose that modulation of the sAC-mediated signaling pathway has therapeutic potential acting on RGC mitochondria for treating glaucoma and other retinal diseases.

Long-Term Systemic Use of Calcium Channel Blockers and Incidence of Primary Open-Angle Glaucoma.

PURPOSE: To evaluate the association between the systemic use of calcium channel blockers (CCBs) and primary open-angle glaucoma (POAG) using a diverse nationwide dataset. DESIGN: Retrospective cohort study. SUBJECTS: 213 424 individuals aged 40 years and older in the National Institutes of Health All of Us dataset, notable for its demographic, geographic, and medical diversity and inclusion of historically underrepresented populations. Patients with a diagnosis of POAG prior to use of any kind of antihypertensive medication were excluded. METHODS: Bivariate and multivariable regression analyses were performed to evaluate associations between CCB use and POAG. Calcium channel blocker use was further divided into exposure to dihydropyridine CCBs and nondihydropyridine CCBs, and subgroup analyses were performed using chi-square and Fisher tests. MAIN OUTCOME MEASURES: Diagnosis of POAG. RESULTS: Within our cohort, 2772 participants (1.3%) acquired a diagnosis of POAG, while 210 652 (98.7%) did not. Among patients who developed POAG, the mean age was 73.3 years, 52.5% were female, and 48.2% identified as White. Among patients with POAG, 32.6% used 1 or more CCB, 28.2% used a dihydropyridine CCB, and 2.2% used a nondihydropyridine CCB. In bivariate analysis, use of any CCBs was associated with an increased risk of POAG (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.27-1.31, P < 0.001). In multivariable analysis adjusting for age, gender, race, ethnicity, and comorbidities such as diabetes, hyperlipidemia, and hypertension, use of any CCBs remained associated with an increased risk of developing POAG (OR: 1.52, 95% CI: 1.33-1.74, P < 0.001). When stratified by type of CCB, the use of dihydropyridine CCBs (OR: 1.31, 95% CI: 1.14-1.50, P < 0.001) was associated with increased POAG risk. CONCLUSIONS: Use of dihydropyridine CCBs was associated with a significantly higher risk of developing POAG, both before and while adjusting for demographic factors and comorbid medical conditions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association between metformin use with circumpapillary retinal nerve fibre layer thickness and capillary vessel density in glaucoma.

BACKGROUND/AIMS: To investigate the association between use of metformin and circumpapillary retinal nerve fibre layer (cpRNFL) thickness, as well as whole image capillary density (wiCD), in patients with glaucoma. METHODS: This cross-sectional study included patients with glaucoma suspect or primary open-angle glaucoma (POAG) underwent optical coherence tomography angiography imaging. Use and duration of antidiabetic medications were assessed at the time of imaging. Multivariable linear mixed-effect modelling was used to estimate the effect of diabetes medication on wiCD and cpRNFL while controlling for covariates including age, race, body mass index, diagnosis, 24-2 visual field mean deviation, and intraocular pressure, average signal strength index as well as any variables that showed a p <0.1 in the univariable analysis. RESULTS: A total of 577 eyes (330 POAG and 247 glaucoma suspect) of 346 patients were included. Sixty-five patients (23%) had diabetes, of whom 55 (78.5%) used metformin, and 17 (26.2%) used insulin. After adjusting for covariates, the association between metformin use and wiCD (1.56 (95% CI 0.40 to 2.71); p=0.008), duration of metformin use and wiCD (0.12 (95% CI 0.02 to 0.22) per 1 year longer; p=0.037), and metformin use and cpRNFL thickness (5.17 (95% CI 1.24 to 9.10) µm; p=0.010) had statistically significant associations in each model. CONCLUSIONS: Metformin use was associated with higher wiCD and thicker cpRNFL. These findings indicate a potential association, underscoring the need for longitudinal studies to determine if metformin plays a role in the retinal conditions of patients with glaucoma. TRIAL REGISTRATION NUMBER: NCT00221897.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle-closure Glaucoma without Cataract: One-year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle-closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle-closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6-18 mm Hg with at least a 20% reduction compared to baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACG were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P=0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P=0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Retinal Nerve Fiber Layer Optical Texture Analysis and 10-2 Visual Field Assessment in Glaucoma.

PURPOSE: To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to 1) investigate the association between papillomacular and papillofoveal bundle defects with 10-2 visual field (VF) sensitivity abnormalities, and 2) integrate the information from RNFL bundle defect and 24-2 VF central test locations to determine the likelihood of 10-2 VF sensitivity abnormalities. DESIGN: Cross-sectional. METHODS: A total of 841 eyes (144 healthy, 317 glaucoma suspect, and 380 glaucoma) of 442 participants were included. Eyes underwent 24-2, and 10-2 VF testing and OCT for ROTA. The borders of RNFL defects were delineated from ROTA, and the involvement of the arcuate, papillomacular, and papillofoveal bundles was determined for each eye. Multilevel logistic regression analysis was applied to evaluate the structure-function association. RESULTS: Papillomacular (92.1%) and papillofoveal (37.9%) RNFL bundle defects were prevalent in eyes with glaucoma. A 10-2 VF location that was projected onto a papillomacular or a papillofoveal RNFL bundle defect had a significantly increased likelihood of reduced sensitivity (ORs of 18.61 at PDP < 5%, and 20.17 at TDP < 5%, respectively, P < .001 for both). When predicting the likelihood of VF abnormality in a 10-2 test location, noticeably higher odds ratios were observed when overlapping with an RNFL bundle defect, compared to when an abnormal corresponding 24-2 central point was present. CONCLUSIONS: Papillomacular and papillofoveal RNFL bundle defects are present in a considerable proportion of eyes with glaucoma. When detected, they significantly increase the likelihood of abnormality in the corresponding central VF test locations assessed by the 10-2 test.

Rate of Initial Optic Nerve Head Capillary Density Loss and Risk of Visual Field Progression.

Importance: Rapid initial optic nerve head capillary density loss may be used to assess the risk of glaucoma visual field progression. Objective: To investigate the association between the rate of initial optic nerve head capillary density loss from optical coherence tomography angiography (OCTA) and visual field progression. Design, Setting, Participants: This was a retrospective study of a longitudinal cohort at a glaucoma referral center. A total of 167 eyes (96 with primary open-angle glaucoma and 71 with glaucoma suspect) of 109 patients were monitored for a mean (SD) of 5.7 (1.4) years from January 2015 to December 2022. Data analysis was undertaken in April 2023. Main Outcomes and Measures: The rates of initial capillary density and average retinal nerve fiber layer loss were calculated from the first 3 optic nerve head OCTA and OCT scans, respectively, during the initial follow-up (mean [SD], 2.0 [1.0] years). Based on the median rate, eyes were categorized into fast and slow progressor groups. The association between initial capillary density change or retinal nerve fiber layer thinning and visual field progression was evaluated using linear-mixed and time-varying Cox models. Results: A total of 167 eyes of 109 patients (mean [SD] age, 69.0 [11.1] years; 56 [51.4%] female and 53 [48.6%] male) were assessed. Eighty-three eyes were slow OCTA progressors, while 84 eyes were fast with mean capillary density loss of -0.45% per year and -1.17% per year, respectively (mean difference, -0.72%/year; 95% CI,-0.84 to -0.60; P < .001). Similarly, 83 eyes were slow OCT progressors, while 84 eyes were fast with mean retinal nerve fiber layer thinning of -0.09 µm per year and -0.60 µm per year, respectively (mean difference, -0.51 µm/year; 95% CI,-0.59 to -0.43; P < .001). The fast OCTA and OCT progressors were associated with more rapid visual field loss (mean difference, -0.18 dB/year; 95% CI,-0.30 to -0.06; P = .004 and -0.17 dB/year; 95% CI,-0.29 to -0.06; P = .002, respectively). Fast OCTA progressing eyes were more likely to have visual field progression (hazard ratio, 1.96; 95% CI, 1.04-3.69; P = .04). Seventeen of 52 eyes (32.7%; 95% CI, 32.5-32.8) with fast OCTA and OCT progression developed subsequent visual field likely progression. Conclusion and Relevance: Rapid initial optic nerve head capillary density loss from OCTA was associated with a faster rate of visual field progression and a doubling of the risk of developing event progression in this study. These findings may support clinical use of OCTA and OCT optic nerve head measurements for risk assessment of glaucoma progression.

VEGF-C and 5-Fluorouracil Improve Bleb Survival in a Rabbit Glaucoma Surgery Trabeculectomy Model.

Purpose: To evaluate VEGF-C-induced lymphoproliferation in conjunction with 5-fluorouracil (5-FU) antimetabolite treatment in a rabbit glaucoma filtration surgery (GFS) model. Methods: Thirty-two rabbits underwent GFS and were assigned to four groups (n = 8 each) defined by subconjunctival drug treatment: (a) VEGF-C combined with 5-FU, (b) 5-FU, (c) VEGF-C, (d) and control. Bleb survival, bleb measurements, and IOP were evaluated over 30 days. At the end, histology and anterior segment OCT were performed on some eyes. mRNA was isolated from the remaining eyes for RT-PCR evaluation of vessel-specific markers (lymphatics, podoplanin and LYVE-1; and blood vessels, CD31). Results: Qualitatively and quantitatively, VEGF-C combined with 5-FU resulted in blebs which were posteriorly longer and wider than the other conditions: vs. 5-FU (P = 0.043 for longer, P = 0.046 for wider), vs. VEGF-C (P < 0.001, P < 0.001) and vs. control (P < 0.001, P < 0.001). After 30 days, the VEGF-C combined with 5-FU condition resulted in longer bleb survival compared with 5-FU (P = 0.025), VEGF-C (P < 0.001), and control (P < 0.001). Only the VEGF-C combined with 5-FU condition showed a negative correlation between IOP and time that was statistically significant (r = -0.533; P = 0.034). Anterior segment OCT and histology demonstrated larger blebs for the VEGF-C combined with 5-FU condition. Only conditions including VEGF-C led to increased expression of lymphatic markers (LYVE-1, P < 0.001-0.008 and podoplanin, P = 0.002-0.011). Expression of CD31 was not different between the groups (P = 0.978). Conclusions: Adding VEGF-C lymphoproliferation to standard antimetabolite treatment improved rabbit GFS success and may suggest a future strategy to improve human GFSs.

Diagnostic Accuracy of Optic Nerve Head and Macula OCT Parameters for Detecting Glaucoma in Eyes With and Without High Axial Myopia.

PURPOSE: To characterize structural differences and assess the diagnostic accuracy of optic nerve head (ONH) and macula optical coherence tomography (OCT) parameters to detect glaucoma in eyes with and without high axial myopia. DESIGN: Cross-sectional study. METHODS: Three hundred sixty-eight glaucoma and 411 healthy eyes with no axial myopia, 393 glaucoma and 271 healthy eyes with mild axial myopia and 124 glaucoma and 85 healthy eyes with high axial myopia were included. Global and sectoral peripapillary retinal nerve fiber layer thickness (pRNFLT), Bruch's membrane opening minimum rim width (BMO-MRW), ganglion cell inner plexiform layer thickness (GCIPLT), and macula RNFLT (mRNFLT) were compared and the diagnostic accuracy for glaucoma detection was evaluated using the adjusted area under the receiver operating characteristic curve (AUC). RESULTS: Diagnostic accuracy for ONH and macula parameters to detect glaucoma was generally high and differed by myopia group. For ONH parameters the diagnostic accuracy was highest for global (AUC = 0.95) and inferotemporal (AUC = 0.91) pRNFLT for high myopes and global BMO-MRW for nonmyopes (AUC = 1.0) and mild myopes (AUC = 0.97). For macula parameters, the diagnostic accuracy was higher in high myopes with 6 of the 11 GCIPLT global/sectors having adjusted AUCs > 0.90 compared to nonhigh myopes with no AUCs > 0.90. In all myopia groups, mRNFLT had lower AUCs than GCIPLT. CONCLUSIONS: The diagnostic accuracy for pRNFL and GCIPL was high for high axial myopic eyes and shows promise for glaucoma detection in high myopes. Further analysis is needed to determine whether the high diagnostic accuracy can be confirmed in other populations.

Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change.

Objective: This study aims to provide data on the effects of glucagon-like peptide 1 receptor (GLP-1R) agonists on intraocular pressure (IOP). Design: Retrospective cohort study. Subjects Participants and/or Controls: 1247 glaucoma surgery and treatment naïve eyes of 626 patients who were initiated on GLP-1R agonists compared to 1083 glaucoma surgery and treatment naïve eyes of 547 patients who were initiated on other oral antidiabetics. Methods Intervention or Testing: The University of California Health Data Warehouse was queried for patients exposed to GLP-1R agonists or other oral antidiabetics. Index date was defined as the date of first exposure to the medication. Eyes with at least one pre-exposure and one post-exposure tonometry record within 365 days of the index date were included in the analysis. Clinical and laboratory data elements were extracted from the database. Eyes were censored from the analysis upon exposure to glaucoma hypotensive medication or glaucoma surgery. ΔIOP was analyzed using a paired t-test. Regression analysis was conducted using generalized estimating equations (GEE) accounting for inter-eye correlation. Sensitivity analyses were performed to assess the robustness of the findings. Main Outcome Measures: Primary outcome measure was ΔIOP after exposure to the medication. Results: The median age of all included subjects was 66.2 years [IQR=18.3]; 607 (51.7%) were female, and 667 (56.9%) were Caucasian. Median pre-exposure IOP, HbA1c, and BMI were 15.2 mmHg [IQR=3.8], 7.5 [IQR=2.4], and 29.8 [IQR=9.4], respectively. 776 individuals (66.1%) had diabetes, with the median number of active oral antidiabetics being 1.0 [IQR=1.0], and 441 (37.5%) being insulin users. Several pre-exposure characteristics significantly differed between the GLP-1R agonist and the control group. The mean ΔIOP was -0.4±2.8 mmHg (paired t-test p<0.001) and -0.2±3.3 mmHg (paired t-test p = 0.297) in the GLP-1R agonist and other antidiabetics groups, respectively. Pre-exposure IOP was the only independent predictor of ΔIOP in multivariable GEE. Sensitivity analyses yielded similar results. Conclusions: Although GLP-1R agonists were significantly associated with a decrease in IOP in the paired analysis, they were not associated with ΔIOP in multivariable GEE. Moreover, the difference between the ΔIOP in the two groups was small. Future prospective studies following a standardized dose and delivery method may provide further insights.