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.

Impact of peripheral anterior synechiae on the outcome of combined phacoemulsification, goniosynechialysis and goniotomy for primary angle-closure glaucoma and cataract: a multicenter observational study.

PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle-closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataract who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into three groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mmHg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred and four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery (P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the three groups (P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared to 180°≤PAS<270° (P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataract over one year period. However, the outcome was not correlated with preoperative extent of PAS. PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle-closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae.

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.

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.

Reduction of Optic Disc Microvasculature and Retinal Nerve Fiber Layer Thinning in Patients with Glaucoma.

PURPOSE: To assess the relationship between the change of optic disc vessel density (ODVD) and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective case series. METHODS: For 105 POAG patients, ≥ 5 consecutive optical coherence tomography (OCT) and OCT angiography (OCTA) images were obtained during ≥ 2 years of follow-up. Based on enface OCTA imaging, ODVD was calculated as the ratio of pixels occupied by vessels below the internal limiting membrane within the temporal area of the optic cup, and ODVD reduction was determined when there was a statistically significant negative slope (P < 0.05) for any of the global, superior, or inferior sectors. The association between the rates of ODVD change and RNFL thinning was assessed by multivariable longitudinal linear mixed-effects model vs. time. RESULTS: During 2.9 ± 0.3 years of follow-up on the 105 participants with visual field mean deviation at baseline of 5.7 ± 4.8 dB, 46 (43.8%) showed ODVD reduction. Faster global RNFL thinning was associated with the smaller Bruch's membrane opening area (ß = 0.381; 95% confidence interval (CI), 0.120 to 0.646; P = 0.006), optic disc hemorrhage (ß = -0.567; 95% CI, -0.909 to -0.228; P = 0.002) and faster rate of global ODVD change (ß = -0.090; 95% CI, -0.139 to -0.042; P = 0.001). CONCLUSIONS: Reduction of optic disc microvasculature was associated with rapid RNFL thinning in POAG. This suggests a role for deep ONH circulation in the glaucoma pathogenesis.

Racial Differences in Diagnostic Accuracy of Retinal Nerve Fiber Layer Thickness in Primary Open-Angle Glaucoma.

Purpose: To evaluate the diagnostic accuracy of retinal nerve fiber layer thickness (RNFLT) by spectral-domain optical coherence tomography (OCT) in primary open-angle glaucoma (POAG) in eyes of African (AD) and European descent (ED). Design: Comparative diagnostic accuracy analysis by race. Participants: 379 healthy eyes (125 AD and 254 ED) and 442 glaucomatous eyes (226 AD and 216 ED) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Methods: Spectralis (Heidelberg Engineering GmbH) and Cirrus (Carl Zeiss Meditec) OCT scans were taken within one year from each other. Main Outcome Measures: Diagnostic accuracy of RNFLT measurements. Results: Diagnostic accuracy for Spectralis-RNFLT was significantly lower in eyes of AD compared to those of ED (area under the receiver operating curve [AUROC]: 0.85 and 0.91, respectively, P=0.04). Results for Cirrus-RNFLT were similar but did not reach statistical significance (AUROC: 0.86 and 0.90 in AD and ED, respectively, P =0.33). Adjustments for age, central corneal thickness, axial length, disc area, visual field mean deviation, and intraocular pressure yielded similar results. Conclusions: OCT-RNFLT has lower diagnostic accuracy in eyes of AD compared to those of ED. This finding was generally robust across two OCT instruments and remained after adjustment for many potential confounders. Further studies are needed to explore the potential sources of this difference.

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: 368 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 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 non-myopes (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 non-high 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.

Optic Disc Microvasculature Dropout in Pre-perimetric Glaucoma.

PURPOSE: To investigate factors associated with optic disc microvasculature dropout (MvD-D) in pre-perimetric primary open-angle glaucoma (PPG) patients. METHODS: 139 eyes of PPG patients were categorized according to the presence of MvD-D with optical coherence tomography angiography (OCTA). Factors including visual field (VF) mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, focal lamina cribrosa (LC) defect, optic disc hemorrhage (DH), and parapapillary deep-layer microvasculature dropout (MvD-P) were compared between eyes with and without MvD-D. RESULTS: MvD-D was observed in 69 PPG eyes (49.6%). Compared with eyes without MvD-D, the ones with MvD-D had a significantly thinner RNFL in all areas except the nasal sector, worse VF MD, and a focal LC defect and MvD-P (P<0.05): male gender also was more highly prevalent. A considerable number of eyes with MvD-D lacked focal LC defect (62.3% (43/69)) or MvD-P (71.0% (49/69)), while a few eyes without MvD-D had focal LC defect (10.0% (7/70)) or MvD-P (2.9% (2/70)). In a multivariable logistic regression analysis, male gender (odds ratio [OR], 3.96; P<0.001), worse VF MD (OR, 1.44; P=0.019), thinner global RNFL (OR, 1.13; P<0.001), higher prevalence of focal LC defect (OR, 3.71; P=0.014) and MvD-P (OR, 7.85; P<0.001) were significantly associated with MvD-D. CONCLUSIONS: MvD-D was related to worse disease severity in PPG patients, and often was not accompanied by focal LC defect or MvD-P. This suggests that impaired optic disc circulation can be an early sign of glaucoma without noticeable changes in functional or structural features (i.e., VF, focal LC defect, MvD-P).

Smoking Intensity is Associated with Progressive Optic Nerve Head Vessel Density loss in Glaucoma.

PURPOSE: To investigate the relationship of smoking and smoking intensity, with the rate of optic nerve head (ONH) whole image capillary density (wiCD) loss in primary open angle glaucoma (POAG) and glaucoma suspect patients. METHODS: In this longitudinal study, POAG patients who had at least 2 years of follow-up and optical coherence tomography angiography (OCTA) performed at a minimum of 4 visits were selected for study. The smoking intensity was calculated as the pack-year at the baseline OCTA. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on the rates of wiCD loss over time. Nonlinear least-squares estimation with piecewise regression model was used to investigate the cutoff point for the relationship between wiCD loss and smoking intensity. RESULTS: 164 eyes (69 glaucoma suspect and 95 POAG) of 110 patients were included with a mean (95% CI) follow-up of 4.0 (3.9 to 4.1) years. Of the 110 patients, 50 (45.5%) had a reported history of smoking. Greater smoking intensity was associated with faster wiCD loss (-0.11 (-0.23 to 0.00)) %/year per 10 pack-year higher; P=0.048) after adjusting for covariates. The wiCD thinning became significantly faster when smoking intensity was greater than 22.2 pack-years. Smoking had no effect on the rate of wiCD thinning in patients who smoked < 22.2 pack-years during their lifetime. CONCLUSIONS: A history of greater smoking consumption was associated with faster vessel density loss, suggesting smoking intensity as a potential risk factor for glaucoma.

Association of Long-Term Intraocular Pressure Variability and Rate of Ganglion Complex Thinning in Patients With Glaucoma.

PURPOSE: To evaluate the association of mean intraocular pressure (IOP) and IOP variability (IOP fluctuation [SD of IOP] and the IOP range) with the rate of ganglion cell complex (GCC) layer thinning over time in patients with glaucoma. DESIGN: Prospective cohort study. METHODS: Participants with at least 4 visits and 2 years of follow-up of optical coherence tomography tests were included. A linear mixed-effect model was used to investigate the association of IOP parameters with the rates of GCC thinning. Subgroup analyses were conducted for eyes with early (MD ≥ -6 dB), and moderate to advanced stage (MD < -6 dB) at baseline. RESULTS: The cohort consisted of 369 eyes of 249 glaucoma patients (282 early glaucoma and 87 moderate to advanced glaucoma) with mean (standard deviation [SD]) age of 68.2 (10.7) years over 5.1 years of follow-up. The mean rate of GCC change was -0.59 (95% confidence interval [CI], -0.67 to -0.52) µm per year. In multivariable models, faster annual rate of GCC thinning was associated with a higher IOP fluctuation (-0.17 [95% CI, -0.23 to -0.11] µm per 1-mmHg higher, P < .001) or higher IOP range (-0.07 [95% CI, -0.09 to -0.05] µm per 1-mmHg higher, P < .001) after adjustment for mean IOP and other confounding factors. Similar results were found for early and moderate to advanced stages of glaucoma. CONCLUSIONS: IOP variability showed an independent association with macular change in patients with glaucoma regardless of severity at baseline, even after adjustment for mean IOP, supporting its potential value as a therapeutic target for clinical decision-making.

Reduced Aqueous Humor Outflow Pathway Arborization in Childhood Glaucoma Eyes.

Purpose: To compare aqueous humor outflow (AHO) pathway patterns between eyes of childhood glaucoma patients and non-glaucomatous patients receiving cataract surgery. Methods: Aqueous angiography was performed in childhood glaucoma eyes (n = 5) receiving glaucoma surgery and in pediatric (n = 1) and healthy adult (n = 5) eyes receiving cataract surgery. Indocyanine green (0.4%) was introduced into the anterior chamber, and AHO was imaged using an angiographic camera (SPECTRALIS HRA+OCT with Flex Module). Images were acquired and analyzed (ImageJ with Analyze Skeleton 2D/3D plugin) from the nasal sides of the eyes, the usual site of glaucoma angle procedures. Image analysis endpoints included AHO vessel length, maximum vessel length, number of branches, number of branch junctions, and vessel density. Results: Qualitatively, childhood glaucoma eyes demonstrated lesser AHO pathway arborization compared to pediatric and adult eyes without glaucoma. Quantitatively, childhood glaucoma and healthy adult cataract eyes showed similar AHO pathway average branch lengths and maximum branch lengths (P = 0.49-0.99). However, childhood glaucoma eyes demonstrated fewer branches (childhood glaucoma, 198.2 ± 35.3; adult cataract, 506 ± 59.5; P = 0.002), fewer branch junctions (childhood glaucoma, 74.6 ± 13.9; adult cataract, 202 ± 41.2; P = 0.019), and lower vessel densities (childhood glaucoma, 8% ± 1.4%; adult cataract, 17% ± 2.5%; P = 0.01). Conclusions: Childhood glaucoma patients demonstrated fewer distal AHO pathways and lesser AHO pathway arborization. These anatomical alternations may result in a new source of trabecular meshwork-independent AHO resistance in this disease cohort. Translational Relevance: Elevated distal outflow pathway resistance due to decreased AHO pathway arborization may explain some cases of failed trabecular bypass surgery in childhood glaucoma.

Activating soluble adenylyl cyclase 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 one of the key regulators of the cAMP/PKA signaling pathway. However, the precise molecular mechanisms underlying the sAC-mediated signaling pathway and mitochondrial protection in RGCs that counter 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, we found that activating 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 in a paraquat oxidative stress model. Notably, sAC activation 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.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Two-year outcomes of anterior versus posterior scleral application of mitomycin C-soaked sponge in trabeculectomy.

PURPOSE: To compare the safety and efficacy of two different application methods of mitomycin C (MMC)-soaked sponge in trabeculectomy. STUDY DESIGN: Retrospective study. METHODS: We included 71 eyes of 71 patients that had undergone trabeculectomy. In the anterior scleral application group, 36 eyes were treated using the long side of the MMC-soaked sponge placed parallel to the limbus. The efficacy and safety in these eyes were compared with eyes treated with the posterior scleral application group, consisting of 35 eyes treated with the long side of the MMC-soaked sponge placed perpendicular to the limbus. The follow-up period was 2 years. The safety of the procedure, including bleb morphology and complications, was the primary outcome, while the success rate was the secondary outcome. RESULTS: The cumulative success rate at 2 years postoperatively was 94.4% in the anterior and and 94.3% in the posterior scleral application group (P = 1.000). However, with the posterior scleral application of the MMC-soaked sponge, blebs were more low-lying (P = 0.048), less in extent (P < 0.001), more normally vascularized (P = 0.027) and more posteriorly directed (P < 0.001). Furthermore, the incidence of thin-walled cystic bleb (P = 0.028) and bleb leakage (P = 0.025) was significantly lower in the posterior scleral application group than in the anterior group. CONCLUSION: Although there were similar success rates, the posterior scleral application of MMC-soaked sponge with trabeculectomy was safer with a better bleb morphology than the anterior scleral application.

Proactive Decision Support for Glaucoma Treatment: Predicting Surgical Interventions with Clinically Available Data.

A longitudinal ophthalmic dataset was used to investigate multi-modal machine learning (ML) models incorporating patient demographics and history, clinical measurements, optical coherence tomography (OCT), and visual field (VF) testing in predicting glaucoma surgical interventions. The cohort included 369 patients who underwent glaucoma surgery and 592 patients who did not undergo surgery. The data types used for prediction included patient demographics, history of systemic conditions, medication history, ophthalmic measurements, 24-2 VF results, and thickness measurements from OCT imaging. The ML models were trained to predict surgical interventions and evaluated on independent data collected at a separate study site. The models were evaluated based on their ability to predict surgeries at varying lengths of time prior to surgical intervention. The highest performing predictions achieved an AUC of 0.93, 0.92, and 0.93 in predicting surgical intervention at 1 year, 2 years, and 3 years, respectively. The models were also able to achieve high sensitivity (0.89, 0.77, 0.86 at 1, 2, and 3 years, respectively) and specificity (0.85, 0.90, and 0.91 at 1, 2, and 3 years, respectively) at an 0.80 level of precision. The multi-modal models trained on a combination of data types predicted surgical interventions with high accuracy up to three years prior to surgery and could provide an important tool to predict the need for glaucoma intervention.

Deep Learning Identifies High-Quality Fundus Photographs and Increases Accuracy in Automated Primary Open Angle Glaucoma Detection.

Purpose: To develop and evaluate a deep learning (DL) model to assess fundus photograph quality, and quantitatively measure its impact on automated POAG detection in independent study populations. Methods: Image quality ground truth was determined by manual review of 2815 fundus photographs of healthy and POAG eyes from the Diagnostic Innovations in Glaucoma Study and African Descent and Glaucoma Evaluation Study (DIGS/ADAGES), as well as 11,350 from the Ocular Hypertension Treatment Study (OHTS). Human experts assessed a photograph as high quality if of sufficient quality to determine POAG status and poor quality if not. A DL quality model was trained on photographs from DIGS/ADAGES and tested on OHTS. The effect of DL quality assessment on DL POAG detection was measured using area under the receiver operating characteristic (AUROC). Results: The DL quality model yielded an AUROC of 0.97 for differentiating between high- and low-quality photographs; qualitative human review affirmed high model performance. Diagnostic accuracy of the DL POAG model was significantly greater (P < 0.001) in good (AUROC, 0.87; 95% CI, 0.80-0.92) compared with poor quality photographs (AUROC, 0.77; 95% CI, 0.67-0.88). Conclusions: The DL quality model was able to accurately assess fundus photograph quality. Using automated quality assessment to filter out low-quality photographs increased the accuracy of a DL POAG detection model. Translational Relevance: Incorporating DL quality assessment into automated review of fundus photographs can help to decrease the burden of manual review and improve accuracy for automated DL POAG detection.

Improving long COVID-related text classification: a novel end-to-end domain-adaptive paraphrasing framework.

The emergence of long COVID during the ongoing COVID-19 pandemic has presented considerable challenges for healthcare professionals and researchers. The task of identifying relevant literature is particularly daunting due to the rapidly evolving scientific landscape, inconsistent definitions, and a lack of standardized nomenclature. This paper proposes a novel solution to this challenge by employing machine learning techniques to classify long COVID literature. However, the scarcity of annotated data for machine learning poses a significant obstacle. To overcome this, we introduce a strategy called medical paraphrasing, which diversifies the training data while maintaining the original content. Additionally, we propose a Data-Reweighting-Based Multi-Level Optimization Framework for Domain Adaptive Paraphrasing, supported by a Meta-Weight-Network (MWN). This innovative approach incorporates feedback from the downstream text classification model to influence the training of the paraphrasing model. During the training process, the framework assigns higher weights to the training examples that contribute more effectively to the downstream task of long COVID text classification. Our findings demonstrate that this method substantially improves the accuracy and efficiency of long COVID literature classification, offering a valuable tool for physicians and researchers navigating this complex and ever-evolving field.

Optic neuropathy in high myopia: Glaucoma or high myopia or both?

Due to the increasing prevalence of high myopia around the world, structural and functional damages to the optic nerve in high myopia has recently attracted much attention. Evidence has shown that high myopia is related to the development of glaucomatous or glaucoma-like optic neuropathy, and that both have many common features. These similarities often pose a diagnostic challenge that will affect the future management of glaucoma suspects in high myopia. In this review, we summarize similarities and differences in optic neuropathy arising from non-pathologic high myopia and glaucoma by considering their respective structural and functional characteristics on fundus photography, optical coherence tomography scanning, and visual field tests. These features may also help to distinguish the underlying mechanisms of the optic neuropathies and to determine management strategies for patients with high myopia and glaucoma.