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.

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.

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 images were obtained during ≥2 years of follow-up. Based on enface OCT angiography 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 < .05) for any of the global, superior, or inferior sectors. The association between the rates of ODVD change and RNFL thinning was assessed by a multivariable longitudinal linear mixed-effects model versus 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], 0.120-0.646; P = .006), optic disc hemorrhage (ß = -0.567; 95% CI, -0.909 to -0.228; P = .002), and faster rate of global ODVD change (ß = -0.090; 95% CI, -0.139 to -0.042; P = .001). CONCLUSIONS: Reduction of optic disc microvasculature was associated with rapid RNFL thinning in POAG. This suggests a role for deep optic nerve head 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.

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.

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.

The influence of orbital architecture on strabismus in craniosynostosis.

PURPOSE: To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis. METHODS: The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children's Hospital (San Diego, CA) from March 2020 to January 2022 were reviewed retrospectively in this masked, case-control study. Computed tomography scans of the orbits were analyzed to obtain dimensions of the orbital entrance and orbital cone. Primary outcome was correlation of strabismus with orbital measurements. RESULTS: A total of 30 orbits from 15 patients with strabismus and 15 controls were included. Craniofacial disorders included in the study were nonsyndromic craniosynostosis (63%), Crouzon syndrome (13%), Apert syndrome (13%), and Pfeiffer syndrome (10%). Orbital index (height:width ratio) (P = 0.01) and medial orbital wall angle (P = 0.04) were found to differ significantly between the strabismus and control groups. CONCLUSIONS: In our small cohort, bony orbital dimensions, including the ratio of orbital height to width and bowing of the medial orbital wall, were associated with strabismus in craniosynostosis.

Time to Glaucoma Progression Detection by Optical Coherence Tomography in Individuals of African and European Descents.

PURPOSE: To examine the time to detectable retinal nerve fiber layer thickness (RNFLT) progression by optical coherence tomography (OCT) among glaucoma patients of African descent (AD) and European descent (ED). DESIGN: Retrospective cohort study. METHODS: AD and ED glaucoma eyes from the Diagnostic Innovations in Glaucoma Study (DIGS)/African Descent and Glaucoma Evaluation Study (ADAGES) with ≥2 years/4 visits of optic nerve head RNFLT measurements were included after homogenization on age, diagnosis, and baseline visual field (VF) measurement. RNFLT variability estimates based on linear mixed-effects models were used to simulate longitudinal RNFLT data for both races. Times to trend-based RNFLT progression detection were calculated under standardized scenarios (same RNFLT baseline/thinning rates for both races) and real-world scenarios (AD and ED cohort-specific RNFLT baseline/thinning rates). RESULTS: We included 332 and 542 eyes (216 and 317 participants) of AD and ED, respectively. In standardized scenarios, the time to detect RNFLT progression appeared to be similar (difference, <0.2 years) for AD and ED across different assumed RNFLT thinning rates/baseline. In real-world scenarios, compared to ED, AD had a faster RNFLT thinning rate (-0.8 vs -0.6 µm/y) and thicker baseline RNFLT (84.6 vs 81.8 µm). With a faster thinning rate, the mean (SD) time to progression detection was shorter in AD (4.8 [2.0] vs ED: 5.4 [2.4] years), and the 5-year progression rate appeared to be higher (AD: 59% vs ED: 47%). CONCLUSIONS: Time to progression detection was similar for both races when assuming identical RNFLT baseline/thinning rates, and shorter in AD eyes under real-world simulation when AD had faster RNFLT thinning. In contrast to prior results on VF, which detected progression later in AD eyes than in ED eyes, OCT may detect progression more consistently across these races.

Racial Differences in the Diagnostic Accuracy of OCT Angiography Macular Vessel Density for Glaucoma.

PURPOSE: To evaluate and compare the diagnostic accuracy of macular vessel density (VD) measured by OCT angiography (OCTA) in individuals of African descent (AD) and European descent (ED) with open-angle glaucoma. DESIGN: Observational, cross sectional study. PARTICIPANTS: A total of 176 eyes of 123 patients with glaucoma and 140 eyes of 88 healthy participants from the Diagnostic Innovations in Glaucoma Study. METHODS: Whole-image ganglion cell complex (wiGCC) thickness and macular VD (parafoveal VD and perifoveal VD) were obtained from 6 × 6 macula scans. Area under the receiver operating characteristic (AUROC) curves were used to evaluate the diagnostic accuracy of macular VD and ganglion cell complex (GCC) thickness in AD and ED participants after adjusting for confounders such as age, visual field mean deviation (VF MD), signal strength index, axial length, self-reported hypertension and diabetes. MAIN OUTCOME MEASURES: Macular VD and wiGCC measurements. RESULTS: Parafoveal and perifoveal VD were significantly lower in ED than AD patients with glaucoma. Parafoveal and perifoveal VD performed significantly worse in AD participants compared with ED participants for detection of glaucoma (adjusted AUROC, 0.75 [95% confidence interval (CI), 0.62, 0.87], 0.85 [95% CI, 0.79, 0.90], P = 0.035; and 0.82 [95% CI, 0.70, 0.92], 0.91 [95% CI, 0.87, 0.94], respectively; P = 0.020). In contrast to VD, diagnostic accuracy of GCC thickness was similar in AD and ED individuals (adjusted AUROC, 0.89 [95% CI, 0.79, 0.96], 0.92 [95% CI, 0.86, 0.96], respectively; P = 0.313). The diagnostic accuracies of both macular VD and GCC thickness for differentiating between glaucoma and healthy eyes increased with increasing VF MD in both AD and ED participants. CONCLUSIONS: Diagnostic performance of OCTA macular VD, but not GCC thickness, for glaucoma detection varies by race. Moreover, macular VD parameters had lower accuracy for detecting glaucoma in AD individuals than in ED individuals. The diagnostic performance of macular VD is race-dependent, and, therefore, race should be taken into consideration when interpreting macular OCTA results. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Axial length and pharmacologic pupillary dilation in highly myopic patients.

PURPOSE: To determine how high myopia impacts pharmacological pupillary dilation, and to evaluate the relationship between the extent of pharmacologic pupillary dilation and axial length. METHODS: Patients were grouped into high myopes, defined as one or both eyes having a refractive error greater than - 6 diopters, and controls (between - 2 and + 2 diopters). Dilation was achieved with 1 drop each of tropicamide 1% and phenylephrine 2.5%. Pupil size was measured at full and dim light prior to dilation, then 15 and 30 min after dilation. Biometry was measured for each patient. Statistical analyses were performed using the Mann-Whitney-Wilcoxon tests, two-sample Welch's t-tests, and linear mixed effect models and generalized estimating equations models accounting for inter-eye correlation. RESULTS: Forty patients (20 high myopes and 20 controls, 80 eyes total) participated in the study. High myopes had larger pupils at baseline and achieved significantly greater pupillary size (7.08 mm, 95% CI: 6.97 to 7.19 mm) than controls (6.23 mm, 95% CI: 5.94 to 6.52 mm) after 30 min of dilation (P < .0005). Fully dilated pupil size at 30 min was significantly correlated with both refractive error (r = - 0.57, P < .0005) and axial length (r = 0.47, P < .0005). Generalized estimating equations and linear mixed effect models identified other predictive variables of pupil size after dilation including age and white-to-white diameter. CONCLUSIONS: Highly myopic patients dilate to a larger pupillary size compared to other patients. Predicting dilation based on extent of myopia could facilitate intraocular surgery planning and reduce clinic wait times for myopic patients.

Deep Learning Estimation of 10-2 Visual Field Map Based on Macular Optical Coherence Tomography Angiography Measurements.

PURPOSE: To develop deep learning (DL) models estimating the central visual field (VF) from optical coherence tomography angiography (OCTA) vessel density (VD) measurements. DESIGN: Development and validation of a deep learning model. METHODS: A total of 1051 10-2 VF OCTA pairs from healthy, glaucoma suspects, and glaucoma eyes were included. DL models were trained on en face macula VD images from OCTA to estimate 10-2 mean deviation (MD), pattern standard deviation (PSD), 68 total deviation (TD) and pattern deviation (PD) values and compared with a linear regression (LR) model with the same input. Accuracy of the models was evaluated by calculating the average mean absolute error (MAE) and the R2 (squared Pearson correlation coefficients) of the estimated and actual VF values. RESULTS: DL models predicting 10-2 MD achieved R2 of 0.85 (95% confidence interval [CI], 74-0.92) for 10-2 MD and MAEs of 1.76 dB (95% CI, 1.39-2.17 dB) for MD. This was significantly better than mean linear estimates for 10-2 MD. The DL model outperformed the LR model for the estimation of pointwise TD values with an average MAE of 2.48 dB (95% CI, 1.99-3.02) and R2 of 0.69 (95% CI, 0.57-0.76) over all test points. The DL model outperformed the LR model for the estimation of all sectors. CONCLUSIONS: DL models enable the estimation of VF loss from OCTA images with high accuracy. Applying DL to the OCTA images may enhance clinical decision making. It also may improve individualized patient care and risk stratification of patients who are at risk for central VF damage.

Prevalence of peripheral retinal findings in retinal patients using ultra-widefield pseudocolor fundus imaging.

Ultra-widefield retinal imaging is increasingly used in ophthalmology and optometry practices to image patients identifying peripheral abnormalities. However, the clinical relevance of these peripheral retinal abnormalities is unclear. This cross-sectional study aims to firstly validate a new grading system, secondly, assess the prevalence of peripheral retinal abnormalities in retinal patients, and finally understand how peripheral findings may associate with retinal disease. Ultra-widefield pseudocolor fundus images were taken from the eyes of clinic patients. Demographic data and clinical diagnosis for each patient was noted. The grading system was validated using masked retinal specialists. Logistic regression identified associations between retinal disease and peripheral retinal findings. Using the grading system, inter-observer agreement was 76.1% with Cohen's Kappa coefficient 0.542 (p < 0.0001) and the test-retest agreement was 95.1% with Kappa 0.677(p < 0.0001). 971 images were included, with 625 eyes (64.4%) having peripheral abnormalities. Peripheral drusen was the most common abnormality (n = 221, 22.76%) and correlated with age-related macular degeneration (p < 0.001). Novel correlations were also identified between diabetic retinopathy and retinal pigmentation as well as pigmentary degeneration. This study provides a validated system for identifying peripheral abnormalities and adds to literature highlighting peripheral retinal associations with retinal disease which would benefit from further study.

Associations of smoking and alcohol consumption with the development of open angle glaucoma: a retrospective cohort study.

OBJECTIVES: To investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma. DESIGN: A retrospective cohort study of patients suspected to have glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). SETTING: Three tertiary glaucoma centres in the USA. PARTICIPANTS: 825 eyes of 610 patients with glaucoma suspect eyes with normal visual fields (VF) at baseline were followed over an average of 9 years from the DIGS and ADAGES studies. OUTCOME MEASURES: Development of glaucoma was defined as occurrence of three consecutive abnormal VF tests during follow-up. Univariable and multivariable Cox regression models were used to investigate lifestyle-related factors associated with development of VF loss over time. RESULTS: VF tests were abnormal three times in a row in 235 (28.5%) eyes. Alcohol consumption was associated with a higher risk of developing glaucoma (HR 1.57, 95% CI 1.03 to 2.38, p=0.037). In men, the risk of developing glaucoma in alcohol drinkers (HR 1.92, 95% CI 1.00 to 3.68, p=0.048) was greater than non-alcohol drinkers. In individuals of African descent, the risk of developing glaucoma in alcohol drinkers (HR 1.79, 95% CI 1.02 to 3.15, p=0.043) was greater than non-alcohol drinkers. Age was a modifier of the relationship between smoking and glaucomatous VF defects (p=0.048). The risk of developing glaucoma in smokers (HR 1.73, 95% CI 1.10 to 2.72, p=0.019) was greater than never smokers after adjustment for confounding factors in older patients (age >61 years). CONCLUSION: Alcohol consumption was associated with an increased risk of developing glaucoma, particularly in men and individuals of African descent. The risk of developing glaucoma among smokers suspected of having glaucoma was influenced by age, with older individuals having a higher risk than younger people. TRIAL REGISTRATION NUMBER: NCT00221897 and NCT00221923.

Trends and practices following the 2016 hydroxychloroquine screening guidelines.

This study aimed to understand the profile of hydroxychloroquine-treated patients, referral patterns, and dosing and to assess the adherence of eye care providers to the latest 2016 screening guidelines provided by the American Academy of Ophthalmology. Patients were identified using electronic health records (EHR) taking hydroxychloroquine and were seen by optometrists, retinal specialists, and non-retinal ophthalmologists. Review of EHR data includes demographic characteristics, indications, and dosing profile of hydroxychloroquine use, eye care provider managing the patient, and imaging modalities performed. A total of 166 patients were included in the study. The most common indications for screening were systemic lupus erythematosus and discoid lupus (52.4%) followed by rheumatoid arthritis (18.7%) and Sjögren's syndrome (9.6%). Ninety-two (55.4%) patients were on a higher-than-recommended dose of > 5 mg/kg/day. Patients who weighed less (mean 63.9 kg) were taking a higher-than-recommended dose (vs. 81.5 kg, p < 0.001). Although retinal specialists adhered best to the use of all three recommended imaging modalities, visual field testing was done appropriately for only 8.3% of Asian and 71.1% of non-Asian patients. In conclusion, there is substantial variability in screening by ophthalmic providers and prescribing practices compared with the current recommendations. In particular, there is a marked deficiency in correct visual field testing in Asian patients. These findings are important to highlight potential interventions to improve screening for hydroxychloroquine toxicity.

Investigating the associations of macular edema in retinitis pigmentosa.

Macular edema (ME), the accumulation of intraretinal fluid in the macula, is a common sight affecting sequelae of retinitis pigmentosa (RP). However, it is unclear why some patients develop ME, and others do not. This study aims to identify associations between clinical-genetic factors in RP with ME. Patients with clinically confirmed RP cases were identified from the inherited retinal disease database at a large tertiary referral academic center. Demographic and genetic testing findings were noted. Additionally, optical coherence tomography volume scans were graded using a validated grading system. One hundred and six patients (73.1%) were found to have ME in at least one eye (OD = 88, mean = 37.9%, OS = 98, mean = 31.7%). Structurally, the presence of epiretinal membrane (ERM) (p < 0.007) and vitreo-macular traction (VMT) (p < 0.003) were significantly associated with ME. Additionally, X-linked (p < 0.032) and autosomal dominant inheritance (p < 0.039) demonstrated a significant association with ME, with RP1 (p < 0.045) and EYS (p < 0.017) pathogenic variants also significantly associated with ME. This study, in a large cohort of RP patients, confirms previous retinal structural associations for ME in RP and identifies potential new genetic associations.

Maintenance Treatment for Metastatic Pancreatic Cancer: Balancing Therapeutic Intensity with Tolerable Toxicity.

Metastatic pancreatic ductal adenocarcinoma is typically treated with multi-agent chemotherapy until disease progression or intolerable cumulative toxicity. For patients whose disease shows ongoing control or response beyond a certain timeframe (≥3-4 months), options include pausing chemotherapy with close monitoring or de-escalating to maintenance therapy with the goal of prolonging progression-free and overall survival while preserving quality of life. There is currently no universally accepted standard of care and a relative dearth of randomized clinical trials in the maintenance setting. Conceptually, such therapy can entail continuing the least toxic components of a first-line regimen and/or introducing novel agent(s) such as the poly(ADP-ribose) polymerase inhibitor olaparib, which is presently the only approved drug for maintenance treatment and is limited to a genetically defined subset of patients. In addition to identifying new therapeutic candidates and combinations in the maintenance setting, including targeted agents and immunotherapies, future research should focus on better understanding this unique biologic niche and how treatment in the maintenance setting may be distinct from resistant/refractory disease; identifying molecular predictors for more effective pairing of specific treatments with patients most likely to benefit; and establishing patient-reported outcomes in clinical trials to ensure accurate capture of quality of life metrics.

Clinical Factors Associated With Long-Term OCT Variability in Glaucoma.

PURPOSE: To examine clinical factors associated with long-term optical coherence tomography (OCT)-measured retinal nerve fiber layer thickness (RNFLT) variability in glaucoma. STUDY DESIGN: Retrospective cohort study. METHODS: Glaucoma eyes from Diagnostic Innovations in Glaucoma Study (DIGS)/the African Descent and Glaucoma Evaluation Study (ADAGES) with ≥2-years and 4-visit follow-up were included. RNFLT variability was calculated per visit as the absolute error of optic nerve head RNFLT residuals across longitudinal follow-up. Clinical factors examined included general demographics, baseline ocular measurements, prior and intervening cataract extraction (CE) or glaucoma surgery, scan quality, baseline RNFLT and RNFLT thinning rate, follow-up duration, and visit/testing frequency. Three multivariable linear mixed models (full model, baseline model, and parsimonious model) were fit to evaluate the effects of clinical factors on RNFLT variability, with 10-fold cross-validation to estimate real-world model performance. RESULTS: A total of 1140 eyes (634 patients) were included. The overall mean (95% CI) RNFLT variability was 1.51(1.45, 1.58) µm. Across different models, African American race (ß [standard error {SE} = 0.18 [0.06]), intervening CE (ß [SE] = 0.52 [0.07]), intervening glaucoma surgeries (ß [SE] = 0.15 [0.03]), and more positive RNFLT thinning rate (ß [SE] = 0.06 [0.02] per 1 µm/y more positive) showed consistent association with greater RNFLT variability, whereas more frequent visits/testing (ß [SE] = -0.11[0.05] per 1 visit/y higher) was associated with smaller RNFLT variability (P < .05 for all). CONCLUSIONS: Relevant clinical factors affecting long-term RNFLT variability in glaucoma were identified. These data enhance the evaluation of longitudinal structural change. Increasing the testing frequency, especially in eyes at risk for higher measurement variability, and resetting of baseline imaging after intervening procedures may help to more reliably detect OCT progression.

The Sensitivity of Ultra-Widefield Fundus Photography Versus Scleral Depressed Examination for Detection of Retinal Horseshoe Tears.

PURPOSE: Ultra-widefield (UWF) imaging is commonly used in ophthalmology in tandem with scleral depressed examinations (SDE) to evaluate peripheral retinal disease. Because of the increased reliance on this technology in tele-ophthalmology, it is critical to evaluate its efficacy for detecting the peripheral retina when performed in isolation. Therefore, we sought to evaluate UWF imaging sensitivity in detecting retinal horseshoe tears (HSTs). STUDY DESIGN: Retrospective clinical validity and reliability study. METHODS: A single-institutional retrospective analysis was performed on patients at the Shiley Eye Institute, University of California, San Diego. Patients with HSTs seen on SDE who underwent treatment with laser were included in the study. A total of 140 patients with HSTs in the right and/or left eyes met the inclusion criteria. Those with concomitant ruptured globes, retinal detachments, and vitreous hemorrhages were excluded. A total of 123 patients with 135 HSTs were included in the final analysis. The primary outcome was the number of HSTs detected by UWF imaging. A secondary outcome was HST location. Sensitivity was measured with respect to HST location, and statistical significance was calculated by Fisher exact testing. RESULTS: A total of 69 (51.1%) HSTs were visualized on UWF images and 66 (48.9%) were not visualized. The sensitivity of UWF imaging in capturing HSTs was 7 of 41 (17.1%), 8 of 25 (32.0%), 7 of 14 (50.0%), and 47 of 55 (85.5%) for the superior, inferior, nasal, and temporal quadrants, respectively. Sensitivities between HST visibility and location were statistically significant (P < .001). CONCLUSIONS: Nearly half of HSTs were missed by UWF imaging. This study demonstrates that UWF imaging alone is not sufficiently sensitive to exclude the presence of HSTs.