Geographic Patterns of Ocular Oncologist Supply and Patient Demand for Uveal Melanoma Treatment in the United States: A Supply and Demand Analysis.

Purpose: To study geographic patterns of supply and demand for uveal melanoma and other ocular oncology healthcare by ocular oncology physicians in the United States. Methods: Google search interest data was obtained through trends.google.com. The combined-state density of ocular oncology physicians was calculated by dividing the number of practicing ocular oncologists in each state and its surrounding states by the state population. Relative search volume (RSV) values were divided by ocular oncology physician density to calculate the Google relative demand index (gRDI) for each state. Medicare (mRDI) and IRIS® Registry (iRDI) relative demand indices were calculated using prevalence data obtained through the Vision and Eye Health Surveillance System (VEHSS). Data from the US Census Bureau and Centers for Disease Control (CDC) databases were also utilized to analyze associations with poverty rates, percent living in urban or rural areas, vision screening rates, and ocular neoplasm rates. Results: Alabama showed the highest RSV (100), while the lowest was reported in New Mexico (20). Vermont had the highest density of combined-state ocular oncology ophthalmologists (1.85 per 100,000 residents). New Mexico had the lowest RDI (0.013 gRDI, 0.015 mRDI, 0.018 iRDI) with 32 combined-state ocular oncologists and a population of 2,114,371. Ocular neoplasm prevalence rates ranged between 1.32% and 5.40% and significantly correlated with RSV. Single-state gRDI correlated with rural status and negatively correlated with urban areas (≥50,000 individuals). Single-state ophthalmologist density correlated positively with percent living in urban areas and vision screening rates, and negatively with rural status. Conclusion: This study uncovered significant heterogeneity in the geographical distribution of ocular oncology physicians and RDI throughout the United States, highlighting potential undersupply scenarios. This may guide efforts to increase ocular oncology physician and surgeon availability in areas of need.

Refractive Error in Inherited Retinal Disease.

PURPOSE: Inherited retinal dystrophies (IRDs) lead to significant vision impairment. Refractive errors (RE) are also associated with vision impairment and an increased risk of ocular comorbidities and may compound impairment caused by IRDs. Identifying the pattern of RE in IRDs may assist in the better management of patients with IRD and provide insights into understanding genetic associations with RE. The aim of this study was to investigate the patterns of RE in patients with IRD from three academic ophthalmology referral centers. DESIGN: Retrospective tri-center cohort study. METHODS: Chart review of clinically and molecularly confirmed IRD cases seen at the University of California San Diego, Oregon Health & Science University, and Children's Hospital Los Angeles. Data retrieved included: demographics, disease phenotype, genotype, best-corrected visual acuity, objective, and/or subjective refraction. RESULTS: A total of 1942 patient notes were reviewed, of these 634 patients (1255 eyes) had refractive data. For genes associated with myopia, NYX (n=14 [1%]) was associated with the highest SER of myopia (mean -9.26 diopters (D) [95% CI -11.867, -6.651], P<0.001) followed by IMPG2 (n=16 [1.1%]) (mean -4.062 D [95% CI -6.254, -1.871], P=0.002), then RPGR (n=104 [7.2%]) (mean -2.664 D [95% CI [-3.618, -1.710], P=0.016) and for genes associated with hyperopia, BEST1 (n= 38 [2.6%]) had the highest SER for hyperopia (mean 2.996 D [95% CI 1.830, 4.162], P<0.001) followed by RS1 (n=26 [1.8%]) (mean 2.562 D [95% CI 1.454, 3.671], P<0.001), then CNGA3 (n=28 [1.9%]) (mean 0.603 D [(95% CI -0.48, 1.686]), P=0.009). Overall patients with IRD were significantly more myopic than age matched population controls. (n=eyes) CONCLUSION: By combining genetic testing with refraction data from a large cohort of patients, we identify IRD genes associated with myopia and hyperopia. However, we find that the pattern of ametropia varies widely not only by gene but also within a gene cohort. The genes identified to be associated with RE are candidates for further in-depth investigation to understand their functional role in RE.

Germline Testing for Veterans with Advanced Prostate Cancer: Concerns about Service-Connected Benefits.

To better understand Veterans' decisions about germline testing, we conducted a single-site, qualitative study of 32 Veterans with advanced prostate cancer. Seven days after oncologist-patient discussions about germline testing, we conducted semi-structured interviews with patients exploring their decision-making process using an interview guide. Four of 14 Veterans with service-connected disability benefits for prostate cancer declined germline testing for fear of losing benefits, as their livelihood depended on these benefits. All 18 Veterans without service-connected benefits agreed to testing. Veterans declining germline testing for this concern can lead to suboptimal cancer care because targeted treatments that could improve their outcomes may go unrecognized. Our findings contributed to new language in the Veterans Benefits Administration Compensation and Pension Manual clarifying that genetic testing showing hereditary predisposition is insufficient to deny service-connected benefits for conditions presumed to be caused by military exposures. Clinicians should communicate this protection when counseling Veterans about genetic testing.

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 individuals of African descent (AD). DESIGN: Retrospective cohort study. METHODS: This multicenter study included eyes with glaucoma from individuals of AD from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study with ≥2 years/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 were 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, and 75th percentile [as p25, median, and p75] slopes and mean slopes). Severity-stratified analyses were also performed. RESULTS: We included 184 eyes from 128 subjects of AD (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 per year for RNFLT, and 0.00, -0.21, -0.30, and -0.51 dB per year for VF MD, respectively. Compared with 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 with that of VF MD progression, in eyes with mild glaucoma (≥1 year earlier) and in eyes with moderate to advanced glaucoma (∼0.5 year earlier). CONCLUSIONS: Computer simulation showed a potentially shorter time to detect RNFLT progression than VF MD progression in eyes from individuals of AD. Our findings support the importance of using RNFLT to detect progressive glaucoma in individuals of AD.

Retinal structural changes after cessation of pentosan polysulfate sodium.

PURPOSE: To quantify baseline and longitudinal structural changes post-cessation in pentosan polysulfate sodium (PPS) retinopathy patients. METHODS: This is a retrospective cohort study. Retinal thickness and volume of choroidal and hyperreflective retinal pigment epithelium (RPE) excrescences were manually segmented from optical coherence tomography (OCT) volume scans. Baseline measurements were compared against age-matched controls. Longitudinal measurements were performed on patients with follow-up data. RESULTS: Twenty-four eyes of 13 patients were included. At baseline, the mean total retinal thickness was lower in the PPS retinopathy cohort than in age and sex-matched controls (269.1 µm vs. 290.2 µm, p = 0.006).The median (range) of follow-up was 18.6 (4.1 to 34.7) months, with the mean last follow-up of 35.2 months after cessation. During the follow-up period, the thickness of the retina decreased significantly by 11.3 µm (CI: 16.8, 5.8) (p<0.001), with an annual mean decrease of 6.70 µm. However, the mean hyperreflective RPE excrescence volume did not change significantly (p = 0.140) over the follow-up period. CONCLUSIONS: Following PPS discontinuation, although RPE excrescence volumes do not change significantly in volume, there continues to be a progressive long-term thinning of the retina which continues at a rate greater than that associated with normal aging. Consequently, long-term follow-up is suggested to monitor patients with PPS maculopathy.

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

PRCIS: Increased oxygen saturation (StO 2 ) was significantly associated with the severity of visual field (VF) damage in patients with glaucoma. OBJECTIVE: To investigate the association between retinal StO 2 percentage and the severity of VF loss in glaucoma. METHODS: A total of 198 eyes from 131 patients with glaucoma were included in this cross-sectional study. Participants underwent imaging using ocular oximetry (Zilia) and 24-2 Swedish Interactive Threshold Algorithm standard VF (Carl Zeiss-Meditec). StO 2 (%) was measured at 2 locations of the peripapillary optic nerve head (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, and StO 2 (%) were calculated. RESULTS: A total of 198 eyes of 131 patients (mean (95% CI) age, 71.1 (68.9,73.3) years, 68 females (51.9%), and 63 males (48.1%) were analyzed. In univariable analysis, higher StO 2 -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 StO 2 was associated with -0.06 (-0.12, -0.00) dB loss in mean deviation in all hemifields ( P = 0.043). In multivariate regression analysis in the superior hemifields, higher StO 2 -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 StO 2. Increased StO 2 was significantly associated with the severity of VF damage in patients with glaucoma.

Evaluation of Retinal Arterial Occlusion and its Visual and Systemic Prognosis after Hyperbaric Oxygen Therapy.

PURPOSE: To evaluate the systemic and ocular outcomes of patients with branch retinal artery occlusion (BRAO) and central retinal artery occlusion (CRAO) after hyperbaric oxygen therapy (HBOT). METHODS: This is a single-institution study of 75 subjects diagnosed with BRAO (28, 37.3%) and CRAO (47, 62.7%) who visited the emergency department or stroke clinic. Twenty-seven (36%) subjects received HBOT on initial presentation (BRAO-14.3%, CRAO-48.9%). The primary outcome was the best corrective visual acuity (BCVA) change in non-HBOT and HBOT subjects. Secondary outcomes included subsequent development of an acute cerebrovascular accident (CVA)/stroke or neovascular glaucoma (NVG). RESULTS: Overall BCVA did not change from the initial presentation to the final timepoint (logMAR 1.5) in either the conservative management or HBOT cohorts for either BRAO subjects (non-HBOT-logMAR 0.4 vs. 0.6, p=0.658; HBOT-logMAR 0.1 vs. 0.4, p=0.207) or CRAO subjects (non-HBOT-logMAR 2.1 vs. 2.2, p=0.755; HBOT-logMAR 2.1 vs. 2.0, p=0.631). Seven (9.3%) subjects developed CVA (BRAO: non-HBOT-4.2% and HBOT-25.0%, p=0.207; CRAO: non-HBOT-16.7% and HBOT-4.3%, p=0.348) and five subjects (6.7%) developed NVG (BRAO: non-HBOT-4.2% and HBOT-0%, p=1.00; CRAO: non-HBOT-16.7% and HBOT-0%, p=0.109). CONCLUSIONS: Our findings suggest that HBOT does not significantly improve BCVA or mitigate the subsequent development of stroke and NVG in patients with RAOs.

Differences in macular thickness associated with peripheral retinal vessel whitening in diabetic patients.

This study aimed to determine the difference in macular thickness among patients with diabetes mellitus (DM) with and without peripheral retinal vessel whitening (PRVW). PRVW was defined by retinal vessel whitening outside the standard seven ETDRS fields. Subjects were divided into DM with PRVW, DM without PRVW, and normal age-matched controls. Optical coherence tomography scans were divided into total, inner, and outer retinal layer thicknesses and were compared in the macula's central, inner, and outer rings. Forty-seven eyes were included: DM with PRVW = 15, DM without PRVW = 16, and Controls = 16. Overall, the mean retinal thickness in patients with DM with PRVW was lower than in patients with DM without PRVW and controls. In the inner macula, DM patients with PRVW showed a significantly lower mean inner superior, nasal, inferior, and temporal macula compared to DM patients without PRVW (p = 0.014, 0.008, 0.005, < 0.001, respectively). DM patients with PRVW also showed a significantly lower mean outer superior, nasal, inferior, and temporal macula than controls (p = 0.005, 0.005, 0.016, 0.025, respectively). This study demonstrates that PRVW in DM patients may be associated with global structural changes to the macular region, promoting a decrease in inner and outer retinal thickness. Further studies should investigate the functional correlation with PRVW in DM patients in order to better understand its potential implications in diabetic patients.

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.

Developing an image-based grading scale for peripheral drusen to investigate associations of peripheral drusen type with age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness. It is associated with peripheral drusen which has not been categorized. We investigated peripheral drusen to validate an image grading system and to understand possible associations between peripheral drusen and AMD. We collated clinical data, ultra-widefield (UWF) pseudocolor fundus images and Spectral-Domain Optical Coherence Tomography (SD-OCT) scans from consecutive retinal patients. SD-OCT scans were used to determine AMD stage. A masked retinal specialist recorded the types of peripheral drusen observed in UWF images. Eyes whose UWF images did not pass quality screening and those without AMD and peripheral drusen were excluded from the study. Statistical tests were utilized to determine the validity of our grading system and associations of peripheral drusen with AMD. A total of 481 eyes (283 subjects) were included in the study (mean age 73.1 ± 1.2years, 64.3% female). Interobserver and test-retest statistical analyses to evaluate the UWF image grading system resulted in Cohen's Kappa 0.649 (p < 0.001) and 0.922 (p < 0.001) respectively. A total of 284 (59.0%), 28 (5.8%), 15 (3.1%), 22 (4.6%), 4 (0.8%), 39 (8.1%), and 32 (6.7%) eyes had hard, soft, reticular, cuticular, atrophic, mixed drusen, and mixed drusen and atrophy respectively in at least one peripheral retinal quadrant. Hard peripheral drusen was significantly associated with the presence of AMD (p = 0.010). Peripheral drusen types were variably seen in retinal patients with and without AMD. We validated a peripheral drusen grading system and provided an image library to assist in the identification of peripheral drusen. Our study found an association between peripheral hard drusen and an AMD diagnosis but did not find a link between peripheral drusen and severity of AMD.

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.

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.

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.

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.

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.

Long-term variability of retinal nerve fibre layer thickness measurement in patients with glaucoma of African and European descents.

BACKGROUND: To examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma. METHODS: This retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races. RESULTS: There were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) µm and 1.42 (1.34, 1.50) µm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p<0.05). In both races, intervening CE was most strongly correlated with higher RNFLT variability (ß: 0.24-0.92, p<0.05). After excluding eyes with intervening CE, RNFLT variability was reduced and the small racial difference was no longer significant (AD: 1.40 (1.31, 1.48) µm vs ED: 1.34 (1.27, 1.40) µm; p=0.280). CONCLUSIONS: Although some predictors were identified, long-term RNFLT variability appeared small for both AD and ED eyes. Moreover, the racial difference did not remain once intervening CE, the strongest predictor of variability, was eliminated. Our findings inform on strategies to optimise structural assessment and suggest that, when accounting for relevant factors, RNFLT is reliable across races.

Association of foveal avascular zone change and glaucoma progression.

BACKGROUND/AIMS: To investigate the association between longitudinal changes of foveal avascular zone (FAZ) area and the rate of structural and functional progression in glaucoma. METHODS: A longitudinal cohort included 115 eyes (46 glaucoma suspect and 66 primary open-angle glaucoma) of 81 patients having ≥2 year follow-up, and ≥4 visits with optical coherence tomography angiography and visual field (VF). Eyes in the longitudinal cohort with a slope greater than that found in 95 percentile of separate healthy test-retest series for FAZ area were categorised into FAZ progressors; all other eyes were defined as FAZ non-progressors. A generalised linear mixed-effect model was used to investigate the association of FAZ progressors with demographic and clinical characteristics. RESULTS: Faster ganglion cell complex (GCC) thinning and faster VF mean deviation (MD) loss were found in eyes with FAZ progressors compared with FAZ non-progressors (mean difference: -0.7 (95% CI, -1.4 to -0.1) µm/y; p=0.026, -0.3 (-0.5 to -0.1) dB/y; p=0.017, respectively), while whole image vessel density was not associated with FAZ progressors (p=0.929). SD of intraocular pressure (IOP) and IOP range were also associated with FAZ progressors in separate multivariable models (OR: 1.54 (1.02 to 2.32) per 1 mm Hg higher, p=0.041; OR: 1.20 (1.01 to 1.41) per 1 mm Hg higher; p=0.035, respectively). CONCLUSIONS: Significant FAZ increase was weakly associated with moderately faster rates of both GCC thinning and VF MD loss, but not macular vessel density change in glaucoma eyes. Additional studies are needed to elucidate the pathophysiological associations between macula GCC thinning and FAZ area increases in glaucoma.