Impact of Smoking on Visual Field Progression in a Long-term Clinical Follow-up.

PURPOSE: To investigate the effect of smoking on rates of progressive visual field (VF) damage over time in glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: Five hundred eleven eyes of 354 patients with glaucoma followed up from multicenter glaucoma registries. METHODS: In this longitudinal study, 354 patients with primary open-angle glaucoma with a minimum of 3 years of follow-up and 5 VF tests were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Univariate and multivariate linear mixed models were used to investigate the effects of smoking on rates of 24-2 VF mean deviation loss. Visual field progression was defined using pointwise linear and significant negative VF mean deviation loss. Logistic regression was used to identify baseline factors and whether different levels of smoking intensity were associated with VF progression. Kaplan-Meier survival analysis and the log-rank test were used to compare the cumulative risk ratio of progression between smoker and never smoker groups. MAIN OUTCOME MEASURES: Visual field progression. RESULTS: Five hundred eleven eyes of 354 patients were included over the median follow-up of 12.5 years. Median baseline age was 64.8 years. Of the 354 patients, 124 (35%) were Black, and 149 (42.1%) and 168 (59.8%) had reported a history of smoking or alcohol consumption, respectively. In a multivariate model, higher smoking intensity was associated with faster VF loss (coefficient, -0.05 decibels (dB)/year per 10 pack-years; 95% confidence interval [CI], -0.08 to -0.01 dB/year per 10 pack-years; P = 0.010). Developing VF progression in eyes of heavy smokers (≥ 20 pack-years) was 2.2 times more than in eyes of patients without smoking history (odds ratio, 2.21; 95% CI, 1.02-4.76; P = 0.044). Statistically significant differences were found between heavy smokers (≥ 20 pack-years) and never smokers by Kaplan-Meier analysis (P = 0.011, log-rank test). CONCLUSIONS: Heavy smokers are more likely to sustain VF loss in eyes with glaucoma. The prospective longitudinal design of this study supports the hypothesis that levels of smoking may be a significant predictor for glaucoma progression. Additionally, this information can be used for clinically relevant tobacco prevention and intervention messages.

Relationship of Choroidal Microvasculature Dropout and Beta Zone Parapapillary Area With Visual Field Changes in Glaucoma.

PURPOSE: To evaluate the association between rates of choroidal microvasculature dropout (MvD) change, beta zone parapapillary atrophy (ß-PPA) area change, and visual field (VF) changes in eyes with primary open-angle glaucoma (POAG). DESIGN: Retrospective, observational cohort study. METHODS: In a tertiary glaucoma clinic, we included 76 eyes from 58 patients with POAG with and without localized MvD, who had ≥2 years of follow-up with a minimum of 4 visits with optical coherence tomography angiography and optical coherence tomography scans. ß-PPA area was evaluated using scanning laser ophthalmoscopy-like images and compared with the area of MvD on an en face choroidal vessel density map during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in ß-PPA area or MvD area and VF mean deviation (MD). RESULTS: Mean rates of change in ß-PPA and MvD area were 0.037 mm2 (95% confidence interval [CI] 0.030-0.043 mm2) per year and 0.039 mm2 (95% CI 0.029-0.048 mm2) per year, respectively, over the mean follow-up of 4.1 years. In multivariable models, MvD area enlargement was significantly associated with faster rates of VF MD loss (0.03 mm2 [95% CI 0.02-0.04 mm2] per 1-dB worse, P < .001) but not ß-PPA area enlargement (0.04 mm2 [95% CI 0.03-0.05 mm2] per 1-dB worse, P = .252). CONCLUSION: MvD area rates, but not ß-PPA area rates, were associated with VF MD loss changes in eyes with POAG. Assessment of MvD is useful for the detection of patients with glaucoma who are at an increased risk of faster VF loss.

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.

Central visual field damage in glaucoma eyes with choroidal microvasculature dropout with and without high axial myopia.

PURPOSE: To characterise the relationship between a deep-layer microvasculature dropout (MvD) and central visual field (VF) damage in primary open-angle glaucoma (POAG) patients with and without high axial myopia. DESIGN: Cross-sectional study. METHODS: Seventy-one eyes (49 patients) with high axial myopia and POAG and 125 non-highly myopic POAG eyes (97 patients) were enrolled. Presence, area and angular circumference of juxtapapillary MvD were evaluated on optical coherence tomography angiography B-scans and en-face choroidal images. RESULTS: Juxtapapillary MvD was detected more often in the highly myopic POAG eyes (43 eyes, 86%) than in the non-highly myopic eyes (73 eyes, 61.9%; p=0.002). In eyes with MvD, MvD area and angular circumference (95% CI) were significantly larger in the highly myopic eyes compared with the non-highly myopic eyes (area: (0.69 (0.40, 0.98) mm2 vs 0.31 (0.19, 0.42) mm2, p=0.011) and (angular circumference: 84.3 (62.9, 105.8) vs 74.5 (58.3, 90.9) degrees, p<0.001), respectively. 24-2 VF mean deviation (MD) was significantly worse in eyes with MvD compared with eyes without MvD in both groups (p<0.001). After adjusting for 24-2 MD VF, central VF defects were more frequently found in eyes with MvD compared with eyes without MvD (82.7% vs 60.9%, p<0.001). In multivariable analysis, higher intraocular pressure, worse 24-2 VF MD, longer axial length and greater MvD area and angular circumference were associated with worse 10-2 VF MD. CONCLUSIONS: MvD was more prevalent and larger in POAG eyes with high myopia than in non-highly myopic POAG eyes. In both groups, eyes with MvD showed worse glaucoma severity and more central VF defects.

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.

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.

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.

Impact of smoking on choroidal microvasculature dropout in glaucoma: a cross-sectional study.

OBJECTIVE: To investigate the effect of smoking on choroidal microvasculature dropout (MvD) in glaucoma. DESIGN: Cross-sectional study. SETTING: Tertiary glaucoma centre. PARTICIPANTS: 223 eyes of 163 patients with primary open-angle glaucoma who had undergone imaging with optical coherence tomography angiography and completed a questionnaire on smoking from the Diagnostic Innovations in Glaucoma Study. PRIMARY OUTCOME MEASURES: Linear mixed-effects models were used to determine the effect of each parameter on MvD area and angular circumference. The sensitivity analysis was performed by categorising the glaucoma severity determined by visual field mean deviation (MD). RESULTS: MvD was found in 37 (51.4%) eyes with smoking history and in 67 (44.4%) eyes with non-smokers (p=0.389). Larger MvD area and wider angular circumference were found in smokers compared with non-smokers (p=0.068 and p=0.046, respectively). In a multivariable model, smoking intensity was significantly associated with MvD area (0.30(95% CI 0.01 to 0.60) each 0.01 mm2 per 10 pack-years; p=0.044). In eyes with moderate-severe glaucoma (MD <-6), smoking intensity was associated with larger MvD area (0.47 (95% CI 0.11 to 0.83) each 0.01 mm2 per 10 pack-years; p=0.011), whereas no significant association was found in early glaucoma (MD ≥-6) (-0.08 (95% CI -0.26 to 0.11), p=0.401). CONCLUSIONS: Smoking intensity was associated with larger choroidal MvD area in eyes with glaucoma, especially in patients with more severe disease. TRIAL REGISTRATION NUMBER: NCT00221897.

Factors associated with choroidal microvascular dropout change.

BACKGROUND/AIMS: To investigate the factors associated with choroidal microvasculature drop-out (MvD) enlargement detected by optical coherence tomography angiography (OCT-A) in glaucomatous eyes. METHODS: Ninety-one eyes of 68 primary open-angle glaucoma patients were enrolled. Only eyes with a minimum of four good quality OCT-A and OCT scans of the optic nerve head acquired at least and with a minimum of 2 years follow-up were included. Area and angular circumference of MvD were analysed on en face images. Univariable and multivariable mixed effects models were constructed to identify the factors contributing to MvD area and angular circumference change over time. RESULTS: Peripapillary MvD was detected in 53 (58.2%) eyes at baseline and in an additional 17 (18.6%) eyes during follow-up, whereas MvD was not detected in 21 (23.0 %) eyes during the entire follow-up period. In multivariable analysis, worse baseline visual field (VF) mean deviation (MD) (ß=0.27, 95% CI 0.10 to 0.44, p=0.002), greater intraocular pressure (IOP) fluctuations (ß=0.86, 95% CI 0.24 to 1.48, p=0.007), higher peak IOP (ß=0.17, 95% CI -0.01 to 0.35, p=0.067) and greater number of IOP lowering medications (ß=1.36, 95% CI 0.67 to 2.05, p<0.001) were associated with faster MvD area enlargement. Worse baseline VF MD and greater IOP fluctuation were also associated with significantly faster MvD circumferential enlargement in multivariable models. CONCLUSION: Greater IOP fluctuation, higher peak IOP, worse baseline VF MD and greater number of glaucoma medications were significantly associated with MvD enlargement in glaucomatous eyes. The identification of factors associated with MvD enlargement may improve our understanding of the role of choroidal vasculature in glaucoma.

Relationship of macular ganglion cell complex thickness to choroidal microvasculature drop-out in primary open-angle glaucoma.

BACKGROUND/AIMS: To investigate the rate of ganglion cell complex (GCC) thinning in primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature drop-out (MvD). METHODS: POAG patients who had at least 1.5 years of follow-up and a minimum of three visits were included from the Diagnostic Innovations in Glaucoma Study. MvD was detected at baseline by optical coherence tomography angiography (OCT-A). Area and angular circumference of MvD were evaluated on en face choroidal vessel density images and horizontal B-scans. Rates of global and hemisphere GCC thinning were compared in MvD and non-MvD eyes using linear mixed-effects models. RESULTS: Thirty-six eyes with MvD and 37 eyes without MvD of 63 patients were followed for a mean of 3.3 years. In 30 out of 36 eyes, MvD was localised in the inferotemporal region. While mean baseline visual field mean deviation was similar between the two groups (p=0.128), global GCC thinning was significantly faster in eyes with MvD than in those without MvD (mean differences: -0.50 (95% CI -0.83 to -0.17) µm/year; p=0.003)). Presence of MvD, area and angular circumference of MvD were independently associated with a faster rate of thinning (p=0.002, p=0.031 and p=0.013, respectively). CONCLUSION: In POAG eyes, GCC thinning is faster in eyes with MvD. Detection of MvD in OCT-A images can assist clinicians to identify patients who are at higher risk for central macula thinning and glaucomatous progression and may require more intensive management.

Effect of Corneal Hysteresis on the Rates of Microvasculature Loss in Glaucoma.

PURPOSE: To investigate the association between corneal hysteresis (CH) and rates of optic nerve head whole image capillary density (wiCD) loss over time in open-angle glaucoma (OAG). DESIGN: Observational cohort. PARTICIPANTS: One hundred seventy-four eyes (122 OAG and 52 glaucoma suspect eyes) from 112 patients over more than 2 years and 4 visits or more. METHODS: Baseline CH measurements were acquired with the Ocular Response Analyzer. Linear mixed-effect models were designed to investigate the effect of CH, average intraocular pressure (IOP) during follow-up, and baseline visual field (VF) mean deviation (MD) on the rates of wiCD loss and circumpapillary retinal nerve fiber layer (cpRNFL) thinning over time, while adjusting for confounders. Interaction between CH or baseline MD and average IOP during follow-up were included in final models to evaluate the effect of baseline MD or average IOP during follow-up on structural changes for different values of CH. MAIN OUTCOME MEASURE: Effect of CH, IOP, and baseline MD on the rates of wiCD loss and cpRNFL thinning over time. RESULTS: The average follow-up time was 3.9 years. In the multivariable model, non-Black race, higher average IOP during follow-up, lower baseline CH, lower baseline VF MD, and higher numbers of IOP-lowering medications were associated with faster rates of wiCD loss over time. For CH values 6 mmHg and 12 mmHg, every 1-mmHg increase in average IOP during follow-up was associated with 0.23% per year faster and 0.07% per year slower rates of wiCD loss over time, respectively. While every 1-mmHg decrease in CH was associated with 1.89% per year faster rate of wiCD loss for MD of -12 dB, it was associated with 0.81% per year faster rate of wiCD loss for MD of -3 dB. CONCLUSION: Lower CH values were significantly associated with faster rates of wiCD loss over time. In eyes with lower CH, both higher average IOP during follow-up and more severe glaucoma damage at baseline were associated with faster rates of wiCD loss and cpRNFL thinning. These results support CH as a useful parameter for risk assessment of glaucoma progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Association Between Rate of Ganglion Cell Complex Thinning and Rate of Central Visual Field Loss.

Importance: Whether rapid ganglion cell complex (GCC) thinning during an initial follow-up period is associated with rates of central visual field loss over time is unclear but important to understand because risk of glaucoma progression can help guide treatment intensity. Objective: To investigate the association between the rate of GCC thinning during initial follow-up and the rate of central visual field loss. Design, Setting, and Participants: This retrospective cohort study assessed patients older than 18 years with glaucoma at a tertiary glaucoma center who were followed up from June 18, 2014, to January 11, 2019. Data analysis for the current study was undertaken in March 2022. Main Outcomes and Measures: Initial rates of GCC thinning were obtained from global GCC thickness values of the first 3 optical coherence tomography (OCT) scans. Rates of central visual field loss were assessed as the change in central (10-2) visual field mean deviation during the 4.7-year follow-up period by univariable and multivariable linear mixed-effects models. Eyes were categorized as slow (>-1 µm/y) or fast (≤-1 µm/y) progressors based on rates of GCC thinning. Results: The cohort consisted of 202 eyes of 139 patients (mean [SD] age, 68.7 [10.0] years; 72 male [51.8%]); 44 African American patients (31.7%), 13 Asian patients (9.4%), 80 White patients (57.6%), and 2 patients who identified as other race and ethnicity (1.4%) were analyzed. The rate of GCC change was -0.56 µm/y (95% CI, -0.66 to -0.46 µm/y) during a mean initial follow-up of 1.8 years (95% CI, 1.7-2.0 years). A total of 163 eyes (80.7%) were slow OCT progressors, and 39 (19.3%) were fast OCT progressors, with rates of GCC thinning of -0.3 µm/y (95% CI, -0.4 to -0.2 µm/y) and -1.6 µm/y (-1.8 to -1.3 µm/y), respectively. The rates of 10-2 visual field mean deviation worsening among slow and fast OCT progressors were -0.10 dB/y (95% CI, -0.16 to 0.00 dB/y) and -0.34 dB/y (95% CI, -0.51 to -0.16 dB/y), respectively (difference, -0.26 dB/y; 95% CI, -0.45 to -0.07 dB/y; P = .008). Conclusions and Relevance: In this cohort study, rapid GCC thinning during an initial follow-up period was associated with faster rates of central visual field decline. These findings support use of longitudinal macular OCT scans assisting clinical decision-making for glaucoma and also may guide possible intensification of therapy in high-risk patients.

Association of Rates of Ganglion Cell and Inner Plexiform Thinning With Development of Glaucoma in Eyes With Suspected Glaucoma.

Importance: In eyes with suspected glaucoma, it is clinically relevant to find diagnostic tests for the risk of development of perimetric glaucoma. Objective: To investigate the association between rates of ganglion cell/inner plexiform layer (GCIPL) and circumpapillary retinal nerve fiber layer (cpRNFL) thinning and the development of perimetric glaucoma in eyes with suspected glaucoma. Design, Setting, and Participants: This observational cohort study used data collected in December 2021 from a tertiary center study and a multicenter study. Participants with suspected glaucoma were followed up for 3.1 years. The study was designed in December 2021 and finalized in August 2022. Exposures: Development of perimetric glaucoma was defined as having 3 consecutive results showing abnormal visual fields. Using linear mixed-effect models, rates of GCIPL were compared between eyes with suspected glaucoma that did and did not develop perimetric glaucoma. A joint longitudinal multivariable survival model was used to investigate the performance of rates of GCIPL and cpRNFL thinning in predicting the risk of developing perimetric glaucoma. Main Outcomes and Measures: Rates of GCIPL thinning and hazard ratio (HR) of developing perimetric glaucoma. Results: Among a total of 462 participants, the mean (SD) age was 63.3 (11.1) years, and 275 patients (60%) were female. Of 658 eyes, 153 eyes (23%) developed perimetric glaucoma. The mean rates of GCIPL thinning were faster in eyes that developed perimetric glaucoma (-1.28 vs -0.66 µm/y for minimum GCIPL thinning; difference, -0.62; 95% CI, -1.07 to -0.16; P = .02). Based on the joint longitudinal survival model, every 1-µm/y faster rate of minimum GCIPL and rate of global cpRNFL thinning were associated with a 2.4 and 1.9 higher risk of developing perimetric glaucoma, respectively (HR, 2.4; 95% CI, 1.8 to 3.2, and HR, 1.99; 95% CI, 1.76 to 2.22, respectively; P < .001). Among the predictive factors, African American race (HR, 1.56; 95% CI, 1.05 to 2.34; P = .02), male sex (HR, 1.47; 95% CI, 1.02 to 2.15; P = .03), 1-dB higher baseline visual field pattern standard deviation (HR, 1.73; 95% CI, 1.56 to 1.91; P < .001), and 1-mm Hg higher mean intraocular pressure during follow-up (HR, 1.11; 95% CI, 1.05 to 1.17; P < .001) were associated with higher risk of developing perimetric glaucoma. Conclusions and Relevance: This study found that faster rates of GCIPL and cpRNFL thinning were associated with higher risks of developing perimetric glaucoma. Rates of cpRNFL thinning and specifically GCIPL thinning may be useful measures for monitoring eyes with suspected glaucoma.

Combining Optical Coherence Tomography and Optical Coherence Tomography Angiography Longitudinal Data for the Detection of Visual Field Progression in Glaucoma.

PURPOSE: To use longitudinal optical coherence tomography (OCT) and OCT angiography (OCTA) data to detect glaucomatous visual field (VF) progression with a supervised machine learning approach. DESIGN: Prospective cohort study. METHODS: One hundred ten eyes of patients with suspected glaucoma (33.6%) and patients with glaucoma (66.4%) with a minimum of 5 24-2 VF tests and 3 optic nerve head and macula images over an average follow-up duration of 4.1 years were included. VF progression was defined using a composite measure including either a "likely progression event" on Guided Progression Analysis, a statistically significant negative slope of VF mean deviation or VF index, or a positive pointwise linear regression event. Feature-based gradient boosting classifiers were developed using different subsets of baseline and longitudinal OCT and OCTA summary parameters. The area under the receiver operating characteristic curve (AUROC) was used to compare the classification performance of different models. RESULTS: VF progression was detected in 28 eyes (25.5%). The model with combined baseline and longitudinal OCT and OCTA parameters at the global and hemifield levels had the best classification accuracy to detect VF progression (AUROC = 0.89). Models including combined OCT and OCTA parameters had higher classification accuracy compared with those with individual subsets of OCT or OCTA features alone. Including hemifield measurements significantly improved the models' classification accuracy compared with using global measurements alone. Including longitudinal rates of change of OCT and OCTA parameters (AUROCs = 0.80-0.89) considerably increased the classification accuracy of the models with baseline measurements alone (AUROCs = 0.60-0.63). CONCLUSIONS: Longitudinal OCTA measurements complement OCT-derived structural metrics for the evaluation of functional VF loss in patients with glaucoma.

Macula structural and vascular differences in glaucoma eyes with and without high axial myopia.

AIMS: To identify clinically relevant parameters for identifying glaucoma in highly myopic eyes, an investigation was conducted of the relationship between the thickness of various retinal layers and the superficial vessel density (sVD) of the macula with axial length (AL) and visual field mean deviation (VFMD). METHODS: 270 glaucoma patients (438 eyes) participating in the Diagnostic Innovations in Glaucoma cross-sectional study representing three axial myopia groups (non-myopia: n=163 eyes; mild myopia: n=218 eyes; high myopia (AL>26 mm): n=57 eyes) who completed macular optical coherence tomography (OCT) and OCT-angiography imaging were included. Associations of AL and VFMD with the thickness of the ganglion cell inner plexiform layer (GCIPL), macular retinal nerve fibre layer (mRNFL), ganglion cell complex (GCC), macular choroidal thickness (mCT) and sVD were evaluated. RESULTS: Thinner Global GCIPL and GCC were significantly associated with worse VFMD (R2=34.5% and R2=32.9%; respectively p<0.001), but not with AL (all p>0.1). Thicker mRNFL showed a weak association with increasing AL (R2=2.4%; p=0.005) and a positive association with VFMD (global R2=19.2%; p<0.001). Lower sVD was weakly associated with increasing AL (R2=1.8%; p=0.028) and more strongly associated with more severe glaucoma VFMD (R2=29.6%; p<0.001). Thinner mCT was associated with increasing AL (R2=15.5% p<0.001) and not associated with VFMD (p=0.194). mRNFL was thickest while mCT was thinnest in all sectors of high myopic eyes. CONCLUSIONS: As thinner GCIPL and GCC were associated with increasing severity of glaucoma but were not significantly associated with AL, they may be useful for monitoring glaucoma in highly myopic eyes.

Relative Stability of Regional Facial and Ocular Temperature Measurements in Healthy Individuals.

Purpose: Non-contact measurement of facial temperature using infrared thermography has been used for mass screening of body temperature during a pandemic. We investigated the relative stability of temperature measurement in different facial regions of healthy individuals. Methods: Twenty healthy subjects underwent two experiments. In the first experiment, subjects washed their faces with a 20°C wet towel for 1 minute. Temperature changes compared to baseline in the forehead, cornea, inner canthus, and outer canthus were determined using an infrared camera for 10 minutes. In the second experiment, lubricating eye drops at 20°C were instilled over one eye. Temperature changes in the same regions of interest were monitored for 5 minutes. Results: Baseline temperatures before face washing in the forehead and cornea, inner canthus, and outer canthus of the right eye were 33.4°C ± 0.8°C (mean ± SD), 33.3°C ± 0.8°C, 34.3°C ± 0.7°C, and 32.8°C ± 0.7°C, respectively. Reductions in temperature due to face washing were most significant for the forehead and least significant for the cornea. One minute after face washing, the corresponding changes were -2.8°C ± 0.6°C, -0.3°C ± 0.6°C, -0.6°C ± 0.7°C, and -0.9°C ± 0.7°C for the forehead, cornea, inner canthus, and outer canthus, respectively. After administering the eye drops, no significant temperature changes were observed. Conclusions: When facial temperature was exogenously cooled, the cornea had the most stable temperature readings. Translational Relevance: When using infrared thermography to screen facial temperature, the measurement of corneal temperature is probably a better representative if the stability of temperature readings is critical.

Human recombinant nerve growth factor (Cenegermin) in a patient affected by primary congenital glaucoma with neurotrophic keratopathy.

PURPOSE: To report a case of neurotrophic keratopathy (NK) in a patient affected by primary congenital glaucoma (PCG) who undergone glaucoma drainage implant surgery. NK was successfully treated with human recombinant Nerve Growth Factor (Cenegermin) eye drops. CASE REPORT DESCRIPTION: A 46-years-old patient affected by primary congenital glaucoma underwent Ahmed glaucoma valve implantation in the right eye, after several unsuccessful surgeries to control intraocular pressure (IOP) since the age of three. Surgical intervention was performed without complications, and IOP was well-controlled post-operatively. However, 1 month after surgery, he developed NK with stromal ulceration, initially treated with a topical combination of preservative-free artificial tears and antibiotic ointment. As NK did not resolve, a new treatment with Cenegermin 20 µg/ml eye drops, 6 times daily, was started. OUTCOME: NK completely resolved after 8 weeks of Cenegermin treatment, with complete restoration of corneal integrity and improvement of corneal sensitivity and transparency. Visual acuity in the operated eye reverted to the pre-operative value. CONCLUSION: Cenegermin was extremely effective in restoring corneal integrity in this PCG patient with NK.

Intraocular pressure increases the rate of macular vessel density loss in glaucoma.

BACKGROUND/AIMS: To evaluate the relationship over time between intraocular pressure (IOP) and the rate of macula whole image vessel density (wiVD) loss and whole image ganglion cell complex (wiGCC) thinning in glaucoma METHODS: From 62 patients in the Diagnostic Innovations in Glaucoma Study, 59 Primary open-angle glaucoma and 27 glaucoma suspect eyes with mean follow-up of 3.2 years were followed. Optical coherence tomography angiography (OCT-A)-based vessel density and OCT-based structural thickness of the same 6×6 mm GCC scan slab were evaluated. Univariable and multivariable linear mixed models were performed for all eyes and also a subset of them in which peak IOP <18 mm Hg to investigate the effect of IOP parameters on the rate of wiVD and wiGCC change. RESULTS: The mean baseline visual field mean deviation (95% CI) was -3.3 dB (-4.4 to -2.1). Higher mean IOP (-0.07%/year per 1 mm Hg (-0.14 to -0.01), p=0.033), peak IOP (-0.07%/year per 1 mm Hg (-0.13 to -0.02), p=0.004) and IOP fluctuation (IOP SD) (-0.17%/year per 1 mm Hg (-0.32 to 0.02), p=0.026) were associated with faster macular vessel density loss. Faster wiGCC thinning was associated with higher mean IOP (-0.05 µm/year per 1 mm Hg (-0.10 to -0.01), p=0.015), peak IOP (-0.05 µm/year per 1 mm Hg (-0.08 to -0.02), p=0.003) and IOP fluctuation (-0.12 µm/year per 1 mm Hg (-0.22 to -0.01), p=0.032). In eyes with peak <18 mm Hg, faster wiVD progression was associated with higher mean IOP (p=0.042). Faster wiGCC progression was associated with higher mean IOP in these eyes (p=0.025). CONCLUSION: IOP metrics were associated with faster rates of overall macular microvascular loss and also in the eyes with peak IOP <18 mm Hg. Future studies are needed to examine whether additional IOP lowering reduces the rate of microvascular loss in patients with glaucoma. TRIAL REGISTRATION NUMBER: NCT00221897.

Rates of Choroidal Microvasculature Dropout and Retinal Nerve Fiber Layer Changes in Glaucoma.

PURPOSE: To evaluate the association between rates of choroidal microvasculature dropout (MvD) change and rates of circumpapillary retinal nerve fiber layer (cpRNFL) loss in primary open-angle glaucoma (POAG) eyes. DESIGN: Cohort study from clinical trial data. METHODS: A total of 91 eyes of 68 POAG patients with and without localized MvD at baseline with at least 4 visits and 2 years of follow-up with optical coherence tomography angiography (OCT-A) and OCT scans were included. Area and angular circumference of MvD were evaluated on OCT-A en face and B-scan choroidal vessel density images during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in MvD area or angular circumference and RNFL thickness. Univariable and multivariable regressions were completed to identify the factors contributing to cpRNFL thinning. RESULTS: MvD was identified in 53 eyes (58.2%) at baseline. Seventeen eyes (18.6%) that did not show MvD at baseline developed it over the follow-up period. Over a mean follow-up of 4.0 years, the mean rates of change in MvD area and angular circumference (95% CI) were 0.05 (0.04, 0.06) mm2 per year and 13.2° (10.7°, 15.8°) per year, respectively. In multivariable models, the rate of cpRNFL thinning was significantly associated with the rates of change in MvD area and angular circumference (P = .008 and P = .009, respectively). CONCLUSIONS: Rates of MvD area and angular circumference change over time were associated with concurrent rates of cpRNFL loss in POAG eyes.