Racial-ethnic disparities in concurrent rates of peripapillary & macular OCT parameters among a large glaucomatous clinical population.

OBJECTIVES: To compare rates of change in peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) parameters among different race-ethnicities from a large electronic health record database of subjects with or suspected of glaucoma. METHODS: In this retrospective cohort study, rates of change were obtained using joint longitudinal linear mixed models for eyes with ≥3 visits and ≥1 year of follow-up, adjusting for age, sex, intraocular pressure, central corneal thickness, and baseline pRNFL and mGCIPL thickness. Best linear unbiased predictor estimates of various parameters were stratified by baseline glaucoma severity and analysed by racial-ethnic group. RESULTS: A total of 21,472 spectral domain optical coherence tomography (OCT) pRNFL scans and 14,431 mGCIPL scans from 2002 eyes were evaluated. A total of 200 (15.6%) and 601 (46.8%) subjects identified as non-Hispanic Black (NHB) and Hispanic, respectively. NHB eyes exhibited faster rates of change in pRNFL among glaucoma suspect (global pRNFL -0.57 ± 0.55 µm/year vs. -0.37 ± 0.62 µm/year among Hispanics, p < 0.001), mild glaucoma (superior pRNFL quadrant -1.20 ± 1.06 µm/year vs. -0.75 ± 1.51 µm/year among non-Hispanic Whites (NHW), p = 0.043), and moderate glaucoma eyes (superior pRNFL quadrant -1.31 ± 1.49 µm/year vs. -0.52 ± 1.26 µm/year among Hispanics, p = 0.003). NHB eyes exhibited faster rates of mGCIPL loss corresponding to pRNFL rates. Global pRNFL and mGCIPL rates were strongly correlated (R2 = 0.70). CONCLUSIONS: Adjusted rates of pRNFL and mGCIPL loss significantly differed between racial-ethnic groups when stratified by glaucoma severity, with faster rates among NHB patients. These differences highlight key racial-ethnic disparities in adjusted rates of glaucoma OCT parameters.

Benefits of tropical peatland rewetting for subsidence reduction and forest regrowth: results from a large-scale restoration trial.

Drainage and deforestation of tropical peat swamp forests (PSF) in Southeast Asia cause carbon emissions and biodiversity loss of global concern. Restoration efforts to mitigate these impacts usually involve peatland rewetting by blocking canals. However, there have been no studies to date of the optimal rewetting approach that will reduce carbon emission whilst also promoting PSF regeneration. Here we present results of a large-scale restoration trial in Sumatra (Indonesia), monitored for 7.5 years. Water levels in a former plantation were raised over an area of 4800 ha by constructing 257 compacted peat dams in canals. We find peat surface subsidence rates in the rewetted restoration area and adjoining PSF to be halved where water tables were raised from ~ - 0.6 m to ~ - 0.3 m, demonstrating the success of rewetting in reducing carbon emission. A total of 57 native PSF tree species were found to spontaneously grow in the most rewetted conditions and in high densities, indicating that forest regrowth is underway. Based on our findings we propose that an effective PSF restoration strategy should follow stepwise rewetting to achieve substantial carbon emission reduction alongside unassisted regrowth of PSF, thereby enabling the peat, forest and canal vegetation to establish a new nature-based ecosystem balance.

Visual Field Outcomes in the Primary Tube Versus Trabeculectomy Study.

PURPOSE: To describe visual field outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study. DESIGN: Cohort analysis. PARTICIPANTS: A total of 155 eyes (155 subjects) randomly assigned to treatment with tube shunt surgery (n = 84) or trabeculectomy with mitomycin C (n = 71). METHODS: The PTVT Study was a multicenter randomized clinical trial comparing the safety and efficacy of trabeculectomy and tube shunt surgery in eyes without previous intraocular surgery. Subjects underwent standard automated perimetry (SAP) at baseline and annually for 5 years. Standard automated perimetry tests were deemed reliable if the false-positive rate was ≤ 15%. Tests were excluded if visual acuity was ≤ 20/400 or loss of ≥ 2 Snellen lines from baseline because of a nonglaucomatous etiology. Linear mixed-effects models were used to compare rates of change in SAP mean deviation (MD) between the 2 groups. Intraocular pressure (IOP) control was assessed by percentage of visits with IOP < 18 mmHg and mean IOP. MAIN OUTCOME MEASURES: Rate of change in SAP MD during follow-up. RESULTS: A total of 730 SAP tests were evaluated (average of 4.7 tests per eye). The average SAP MD at baseline was -12.8 ± 8.3 decibels (dB) in the tube group and -12.0 ± 8.4 dB in the trabeculectomy group (P = 0.57). The mean rate of change in SAP MD was -0.32 ± 0.39 dB/year in the trabeculectomy group and -0.47 ± 0.43 dB/year in the tube group (P = 0.23). Eyes with mean IOP 14 to 17.5 mmHg had significantly faster rates of SAP MD loss compared with eyes with mean IOP < 14 mmHg (-0.59 ± 0.13 vs. -0.27 ± 0.08 dB/year; P = 0.012), and eyes with only 50% to 75% of visits with IOP < 18 mmHg had faster rates than those with 100% of visits with IOP < 18 mmHg (-0.90 ± 0.16 vs. -0.29 ± 0.08 dB/year; P < 0.001). Multivariable analysis identified older age and worse IOP control as risk factors for faster progression in both treatment groups. CONCLUSIONS: No statistically significant difference in mean rates of visual field change was observed between trabeculectomy and tube shunt surgery in the PTVT Study. Worse IOP control was significantly associated with faster rates of SAP MD loss during follow-up. Older patients were also at risk for faster progression.

Performance of Linear Mixed Models in Estimating Structural Rates of Glaucoma Progression Using Varied Random Effect Distributions.

Purpose: To compare how linear mixed models (LMMs) using Gaussian, Student t, and log-gamma (LG) random effect distributions estimate rates of structural loss in a glaucomatous population using OCT and to compare model performance to ordinary least squares (OLS) regression. Design: Retrospective cohort study. Subjects: Patients in the Bascom Palmer Glaucoma Repository (BPGR). Methods: Eyes with ≥ 5 reliable peripapillary retinal nerve fiber layer (RNFL) OCT tests over ≥ 2 years were identified from the BPGR. Retinal nerve fiber layer thickness values from each reliable test (signal strength ≥ 7/10) and associated time points were collected. Data were modeled using OLS regression as well as LMMs using different random effect distributions. Predictive modeling involved constructing LMMs with (n - 1) tests to predict the RNFL thickness of subsequent tests. A total of 1200 simulated eyes of different baseline RNFL thickness values and progression rates were developed to evaluate the likelihood of declared progression and predicted rates. Main Outcome Measures: Model fit assessed by Watanabe-Akaike information criterion (WAIC) and mean absolute error (MAE) when predicting future RNFL thickness values; log-rank test and median time to progression with simulated eyes. Results: A total of 35 862 OCT scans from 5766 eyes of 3491 subjects were included. The mean follow-up period was 7.0 ± 2.3 years, with an average of 6.2 ± 1.4 tests per eye. The Student t model produced the lowest WAIC. In predictive models, all LMMs demonstrated a significant reduction in MAE when estimating future RNFL thickness values compared with OLS (P < 0.001). Gaussian and Student t models were similar and significantly better than the LG model in estimating future RNFL thickness values (P < 0.001). Simulated eyes confirmed LMM performance in declaring progression sooner than OLS regression among moderate and fast progressors (P < 0.01). Conclusions: LMMs outperformed conventional approaches for estimating rates of OCT RNFL thickness loss in a glaucomatous population. The Student t model provides the best model fit for estimating rates of change in RNFL thickness, although the use of the Gaussian or Student t distribution in models led to similar improvements in accurately estimating RNFL loss. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Socioeconomic Disparities in Glaucoma Severity at Initial Diagnosis: A Nationwide Electronic Health Record Cohort Analysis.

PURPOSE: To assess disparities in initial disease severity among open-angle glaucoma (OAG) patients. DESIGN: Cross-sectional study. METHODS: In this analysis of Epic Cosmos, an aggregated electronic health record dataset encompassing >213 million patients, OAG patients examined in ophthalmology or optometry clinics between January 1, 2013, and June 1, 2023, were evaluated. OAG severity at presentation was classified as mild, moderate, or severe using International Classification of Disease-10 codes. Demographics, social vulnerability index (SVI) scores, and rural-urban commuting area codes were evaluated as predictors of disease stage using ordinal logistic regression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Of 245,669 patients, 38.1% had mild, 32.5% moderate, and 29.3% severe disease at presentation. In multivariable analyses, significant determinants of worse severity included older age (OR: 1.23 per decade, 95% CI: 1.22-1.23), male sex (OR: 1.37, 95% CI: 1.35-1.39), Black race (OR: 1.61, 95% CI: 1.58-1.65), Hispanic ethnicity (OR: 1.15, 95% CI: 1.11-1.18), non-commercial insurance or uninsured status (OR: 2.53, 95% CI: 2.33-2.74), secondary OAGs (eg, pseudoexfoliative glaucoma - OR: 1.65, 95% CI: 1.58-1.72), and higher socioeconomic SVI scores (OR: 1.25 for highest versus lowest quartile, 95% CI: 1.22-1.28). Black and Hispanic patients were diagnosed at younger ages compared to White patients (mean ages: 67.8 ± 12.3 and 68.1 ± 12.8 vs 73.3 ± 11.8 years respectively, P < .001). CONCLUSIONS: Worse OAG at presentation was associated with older age, male sex, Black race, Hispanic ethnicity, non-commercial insurance or uninsured status, secondary OAGs, and greater socioeconomic vulnerability in this nationwide cohort. These findings can help tailor screening programs towards vulnerable populations.

Short-term Detection of Fast Progressors in Glaucoma: The Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study.

PURPOSE: To evaluate the performance of an intensive, clustered testing approach in identifying eyes with rapid glaucoma progression over 6 months in the Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 125 eyes from 65 primary open-angle glaucoma (POAG) subjects. METHODS: Subjects underwent 2 sets of 5 weekly visits (clusters) separated by an average of 6 months and then were followed with single visits every 6 months for an overall mean follow-up of 25 months (mean of 17 tests). Each visit consisted of testing with standard automated perimetry (SAP) 24-2 and 10-2, and spectral-domain OCT (SD-OCT). Progression was assessed using trend analyses of SAP mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness. Generalized estimating equations were applied to adjust for correlations between eyes for confidence interval (CI) estimation and hypothesis testing. MAIN OUTCOME MEASURES: Diagnostic accuracy of the 6-month clustering period to identify progression detected during the overall follow-up. RESULTS: A total of 19 of 125 eyes (15%, CI, 9%-24%) progressed based on SAP 24-2 MD over the 6-month clustering period. A total of 14 eyes (11%, CI, 6%-20%) progressed on SAP 10-2 MD, and 16 eyes (13%, CI, 8%-21%) progressed by RNFL thickness, with 30 of 125 eyes (24%, CI, 16%-34%) progressing by function, structure, or both. Of the 35 eyes progressing during the overall follow-up, 25 had progressed during the 6-month clustering period, for a sensitivity of 71% (CI, 53%-85%). Of the 90 eyes that did not progress during the overall follow-up, 85 also did not progress during the 6-month period, for a specificity of 94% (CI, 88%-98%). Of the 14 eyes considered fast progressors by SAP 24-2, SAP 10-2, or SD-OCT during the overall follow-up, 13 were identified as progressing during the 6-month cluster period, for a sensitivity of 93% (CI, 66%-100%) for identifying fast progression with a specificity of 85% (CI, 77%-90%). CONCLUSIONS: Clustered testing in the Fast-PACE Study detected fast-progressing glaucoma eyes over 6 months. The methodology could be applied in clinical trials investigating interventions to slow glaucoma progression and may be of value for short-term assessment of high-risk subjects. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.

System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.

Hepatitis B infection caused by the hepatitis B virus is a life-threatening cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Researchers have produced multiple in vivo models for hepatitis B virus (HBV) and, currently, there are no specific laboratory animal models available to study HBV pathogenesis or immune response; nonetheless, their limitations prevent them from being used to study HBV pathogenesis, immune response, or therapeutic methods because HBV can only infect humans and chimpanzees. The current study is the first of its kind to identify a suitable chemically induced liver cirrhosis/HCC model that parallels HBV pathophysiology. Initially, data from the peer-reviewed literature and the GeneCards database were compiled to identify the genes that HBV and seven drugs (acetaminophen, isoniazid, alcohol, D-galactosamine, lipopolysaccharide, thioacetamide, and rifampicin) regulate. Functional enrichment analysis was performed in the STRING server. The network HBV/Chemical, genes, and pathways were constructed by Cytoscape 3.6.1. About 1546 genes were modulated by HBV, of which 25.2% and 17.6% of the genes were common for alcohol and lipopolysaccharide-induced hepatitis. In accordance with the enrichment analysis, HBV activates the signaling pathways for apoptosis, cell cycle, PI3K-Akt, TNF, JAK-STAT, MAPK, chemokines, NF-kappa B, and TGF-beta. In addition, alcohol and lipopolysaccharide significantly activated these pathways more than other chemicals, with higher gene counts and lower FDR scores. In conclusion, alcohol-induced hepatitis could be a suitable model to study chronic HBV infection and lipopolysaccharide-induced hepatitis for an acute inflammatory response to HBV.

Pattern Electroretinogram in Ocular Hypertension, Glaucoma Suspect and Early Manifest Glaucoma Eyes: A Systematic Review and Meta-analysis.

Topic: To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes in normal controls as compared to ocular hypertension (OHT), glaucoma suspect (GS), or early manifest glaucoma (EMG) eyes. Clinical Relevance: The identification of standardized confidence limits in the context of pattern electroretinogram (PERG) might overcome the high intrinsic variability of the measure, and it might lead to a more intuitive understanding of the results as well as to an easier comparison of data from multiple tests, sites, and operators. Methods: The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (ID: CRD42022370032). A literature search was conducted on PubMed, Web of Science, and Scopus. Studies comparing PERG raw data in normal control eyes as compared to OHT, GS, or EMG were included. The risk of bias was assessed using the National Institute for Health and Clinical Excellence quality assessment tool. The main outcome was the P50, N95, and ssPERG amplitude difference between the control and the study groups' eyes. The standardized mean difference was calculated as a measure of the effect size for the primary outcome. A subanalysis was conducted based on the type of electrodes adopted for the PERG measurements (invasive vs. noninvasive). Results: Of the 4580 eligible papers, only 23 were included (1754 eyes). Statistically significant amplitude differences were found in the P50, N95, and ssPERG amplitudes between normal controls and OHT, GS, and EMG eyes. The highest standardized mean difference values were observed in the ssPERG amplitude in all 3 sets of comparison. The subanalysis did not reveal any statistically significant differences between invasive and noninvasive recording strategies. Conclusions: The use of standardized values as the main outcome measures in the context of the PERG data analysis is a valid approach, normalizing several confounding factors which have affected the clinical utility of PERG both for individual patients and in clinical trials. Steady state PERG apparently better discriminates diseased eyes compared to tPERG. The adoption of skin-active electrodes is able to adequately discriminate between healthy and diseased statuses. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Immediate sequential vs delayed sequential bilateral cataract surgery: systematic review and meta-analysis.

The main aim of this systematic review and meta-analysis was to evaluate the safety and efficacy profile of immediate sequential bilateral cataract surgery (ISBCS) compared with delayed sequential bilateral cataract surgery (DSBCS). MEDLINE Ovid, EMBASE, and CENTRAL databases were searched. Outcome measures were postoperative visual acuity, postoperative spherical equivalent (refractive outcome), endophthalmitis, corneal edema, pseudophakic macular edema, and posterior capsule rupture (PCR). 13 articles met criteria for final inclusion. A total of 11 068 622 participants (18 802 043 eyes) were included. No statistically significant differences between ISBCS and DSBCS were identified in all the postoperative outcomes evaluated. However, a higher risk for PCR was identified in the ISBCS group from the pooled analysis of nonrandomized studies (risk ratio, 1.34, 95% CI, 1.08-1.67, P = .0081). In our view, the ISBCS approach has an acceptable safety-efficacy profile, comparable with DSBCS. Future investigations are warranted, with a focus on the analysis of risk factors for surgical complications, patient-reported outcome-measures, and cost effectiveness.

Improved Prediction of Perimetric Loss in Glaucomatous Eyes Using Latent Class Mixed Modeling.

PURPOSE: To evaluate whether the identification of distinct classes within a population of glaucoma patients improves estimates of future perimetric loss. DESIGN: Longitudinal cohort study. PARTICIPANTS: A total of 6558 eyes of 3981 subjects from the Duke Ophthalmic Registry with ≥ 5 reliable standard automated perimetry (SAP) tests and ≥ 2 years of follow-up. METHODS: Standard automated perimetry mean deviation (MD) values were extracted with associated timepoints. Latent class mixed models (LCMMs) were used to identify distinct subgroups (classes) of eyes according to rates of perimetric change over time. Rates for individual eyes were then estimated by considering both individual eye data and the most probable class membership for that eye. Data were split into training (80%) and test sets (20%), and test set mean squared prediction errors (MSPEs) were estimated using LCMM and ordinary least squares (OLS) regression. MAIN OUTCOME MEASURES: Rates of change in SAP MD in each class and MSPE. RESULTS: The dataset contained 52 900 SAP tests with an average of 8.1 ± 3.7 tests per eye. The best-fitting LCMM contained 5 classes with rates of -0.06, -0.21, -0.87, -2.15, and +1.28dB/year (80.0%, 10.2%, 7.5%, 1.3%, and 1.0% of the population, respectively) labeled as slow, moderate, fast, catastrophic progressors, and "improvers" respectively. Fast and catastrophic progressors were older (64.1 ± 13.7 and 63.5 ± 16.9 vs. 57.8 ± 15.8, P < 0.001) and had generally mild-moderate disease at baseline (65.7% and 71% vs. 52%, P < 0.001) than slow progressors. The MSPE was significantly lower for LCMM compared to OLS, regardless of the number of tests used to obtain the rate of change (5.1 ± 0.6 vs. 60.2 ± 37.9, 4.9 ± 0.5 vs. 13.4 ± 3.2, 5.6 ± 0.8 vs. 8.1 ± 1.1, 3.4 ± 0.3 vs. 5.5 ± 1.1 when predicting the fourth, fifth, sixth, and seventh visual fields (VFs) respectively; P < 0.001 for all comparisons). MSPE of fast and catastrophic progressors was significantly lower with LCMM versus OLS (17.7 ± 6.9 vs. 48.1 ± 19.7, 27.1 ± 8.4 vs. 81.3 ± 27.1, 49.0 ± 14.7 vs. 183.9 ± 55.2, 46.6 ± 16.0 vs. 232.4 ± 78.0 when predicting the fourth, fifth, sixth, and seventh VFs respectively; P < 0.001 for all comparisons). CONCLUSIONS: Latent class mixed model successfully identified distinct classes of progressors within a large glaucoma population that seemed to reflect subgroups observed in clinical practice. Latent class mixed models were superior to OLS regression in predicting future VF observations. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosuremay be found after the references.

Effect of SPARC Suppression in Mice, Perfused Human Anterior Segments, and Trabecular Meshwork Cells.

Purpose: Secreted protein, acidic and rich in cysteine (SPARC) elevates intraocular pressure (IOP), increases certain structural extracellular matrix (ECM) proteins in the juxtacanalicular trabecular meshwork (JCT), and decreases matrix metalloproteinase (MMP) protein levels in trabecular meshwork (TM) endothelial cells. We investigated SPARC as a potential target for lowering IOP. We hypothesized that suppressing SPARC will decrease IOP, decrease structural JCT ECM proteins, and alter the levels of MMPs and/or their inhibitors. Methods: A lentivirus containing short hairpin RNA of human SPARC suppressed SPARC in mouse eyes and perfused cadaveric human anterior segments with subsequent IOP measurements. Immunohistochemistry determined structural correlates. Human TM cell cultures were treated with SPARC suppressing lentivirus. Quantitative reverse transcriptase polymerase chain reaction (PCR), immunoblotting, and zymography determined total RNA, relative protein levels, and MMP enzymatic activity, respectively. Results: Suppressing SPARC decreased IOP in mouse eyes and perfused human anterior segments by approximately 20%. Histologically, this correlated to a decrease in collagen I, IV, and VI in both the mouse TM and human JCT regions; in the mouse, fibronectin was also decreased but not in the human. In TM cells, collagen I and IV, fibronectin, MMP-2, and tissue inhibitor of MMP-1 were decreased. Messenger RNA of the aforementioned genes was not changed. Plasminogen activator inhibitor 1 (PAI-1) was upregulated in vitro by quantitative PCR and immunoblotting. MMP-1 activity was reduced in vitro by zymography. Conclusions: Suppressing SPARC decreased IOP in mice and perfused cadaveric human anterior segments corresponding to qualitative structural changes in the JCT ECM, which do not appear to be the result of transcription regulation.

The Effect of Changing Fellowship Interview Format on Candidate Ranking Variabilities: The COVID-19 Experience.

Purpose: This study investigated the effect of interview format changes (in-person to virtual, one-to-one to multiple-to-one) necessitated by the COVID-19 travel restrictions on preliminary fellowship candidate ranking variabilities. Design: Cross-sectional observational study. Method: In 2018 and 2019, the glaucoma fellowship interviews were conducted in-person in a one-to-one format, whereas in 2020, interviews were virtual and in a multiple (interviewers)-to-one (candidate) format. We compared ranking ranges of interviewers within the same virtual room (WSR) and not within the same virtual room (NWSR) to assess the effect of WSR versus NWSR on ranking variabilities. We also compared ranking categories ("accept," "alternate," and "pass") agreements between 2018, 2019, and 2020 to assess the effect of virtual versus in-person interviews on ranking variabilities. Results: NWSR and WSR mean rankings differed by 1.33 (95% confidence interval difference 0.61 to 2.04, p = 0.0003), with WSR interviewers having less variability than NWSR pairs. The variability between 2018/2019 (in-person interviews) and 2020 (virtual interviews) showed no differences between in-person and virtual interviews (weighted Kappa statistic 0.086 for 2018, 0.158 for 2019, and 0.101 for 2020; p < 0.05 for all years). The overall least attractive candidate has the lowest variability; the most attractive candidate has the second lowest variability. Conclusion: Grouping interviewers WSR during the interview decreased ranking variabilities compared to NWSR, while a change from in-person to virtual interview format did not increase the ranking variabilities. This suggests that the decreased nonverbal interactions in virtual interviews do not decrease interviewers' perceptions as applied to preliminary rankings.

Glaucoma Cascade Screening in a High Risk Afro-Caribbean Haitian Population: A Pilot Study.

PRCIS: Glaucoma cascade screening in first-degree relatives (FDRs) of young Haitian glaucoma patients had high yield for diagnosing manifest and suspected glaucoma in 30.8% of those screened despite modest participation. PURPOSE: To evaluate the outcomes of glaucoma cascade screening in FDRs (parents, siblings, and offspring) of Haitian juvenile open-angle glaucoma (JOAG) patients. PATIENTS AND METHODS: Consecutive index patients (Haitians with JOAG) were identified, and the number/type of FDRs residing in South Florida were recorded. These FDRs were invited for free glaucoma screening, which included a comprehensive ophthalmic exam, gonioscopy, automated visual field testing and optical coherence tomographic analysis of the retinal nerve fiber layers. FDR characteristics and clinical findings from screening are reported. RESULTS: A total of 77 FDRs were invited, 26 (33.8%) agreed to undergo screening (18 females, 9 males), which revealed 2 (7.7%) with manifest glaucoma (mean age 77.5 y; one of whom was previously unaware of his glaucoma diagnosis), 6 (23.1%) with suspected glaucoma (mean age 29.8±18.3 y), and 18 (69.2%) without manifest or suspected glaucoma (mean age 37.2±21.8 y). Siblings of index patients were least likely to participate in cascade glaucoma screening when compared with index patients' parents or offspring. FDR eyes with manifest glaucoma had significantly worse best-corrected visual acuities, higher intraocular pressures, thinner central corneal thicknesses, and thinner circumferential papillary retinal nerve fiber layer thicknesses than those without glaucoma. CONCLUSION: Glaucoma cascade screening of Haitian JOAG patients' FDRs revealed that 30.8% had suspected or manifest glaucoma. Future efforts centered on provider-initiated recruitment and improving public glaucoma awareness and education may increase screening participation.

Rates of Glaucoma Progression Derived from Linear Mixed Models Using Varied Random Effect Distributions.

PURPOSE: To compare the ability of linear mixed models with different random effect distributions to estimate rates of visual field loss in glaucoma patients. METHODS: Eyes with five or more reliable standard automated perimetry (SAP) tests were identified from the Duke Glaucoma Registry. Mean deviation (MD) values from each visual field and associated timepoints were collected. These data were modeled using ordinary least square (OLS) regression and linear mixed models using the Gaussian, Student's t, or log-gamma (LG) distributions as the prior distribution for random effects. Model fit was compared using the Watanabe-Akaike information criterion (WAIC). Simulated eyes of varying initial disease severity and rates of progression were created to assess the accuracy of each model in predicting the rate of change and likelihood of declaring progression. RESULTS: A total of 52,900 visual fields from 6558 eyes of 3981 subjects were included. Mean follow-up period was 8.7 ± 4.0 years, with an average of 8.1 ± 3.7 visual fields per eye. The LG model produced the lowest WAIC, demonstrating optimal model fit. In simulations, the LG model declared progression earlier than OLS (P < 0.001) and had the greatest accuracy in predicted slopes (P < 0.001). The Gaussian model significantly underestimated rates of progression among fast and catastrophic progressors. CONCLUSIONS: Linear mixed models using the LG distribution outperformed conventional approaches for estimating rates of SAP MD loss in a population with glaucoma. TRANSLATIONAL RELEVANCE: Use of the LG distribution in models estimating rates of change among glaucoma patients may improve their accuracy in rapidly identifying progressors at high risk for vision loss.

Role of Caspase-1 as a Biomarker of Ocular Surface Damage.

PURPOSE: To examine the potential of caspase-1 as a biomarker for ocular surface damage. DESIGN: Cross-sectional study. METHODS: A total of 113 tear samples (64 subjects) were analyzed. Sixty-one samples were from individuals with dry eye disease (DED), defined as Ocular Surface Disease Index (OSDI) ≥13 and/or corneal staining (CS) ≥3; 32 were from individuals who used glaucoma medication, irrespective of DED metrics; and 20 were from controls (CS <3 and OSDI <13). All individuals completed a medical history form and underwent an ocular surface assessment. Protein levels of caspase-1 were determined by enzyme-linked immunosorbent assay off Schirmer's strips. The primary analysis compared caspase-1 levels in individuals with signs of ocular surface damage (CS ≥3) in both case groups and controls. Secondary correlational analyses were conducted to examine relationships between caspase-1 levels and ocular signs and symptoms. Finally, area under the curve (AUC) analyses were performed to examine relationships between inflammatory markers and CS. RESULTS: The mean age of the population was 58±18 years; 70% were female. Tear samples from individuals with ocular surface damage presented higher caspase-1 levels than the control group. Caspase-1 levels showed a moderate positive correlation with CS (Spearman r = 0.31; P = .001) and eye redness (Spearman r = 0.39; P = .004), and a negative correlation with Schirmer's (Spearman r = -0.46; P < .001) and tear break-up time (Spearman r = -0.33; P = .0006). Caspase-1 showed higher sensitivity and AUC for detecting ocular surface damage than InflammaDry, and its expression was not affected by anti-inflammatory agents. CONCLUSION: Caspase-1 levels were higher in the tears of individuals with ocular surface damage, suggesting its potential to be used as a biomarker and/or therapeutic target.

Risk Factors for Corneal Striae in Eyes After Glaucoma Surgery.

PRCIS: Eyes with corneal striae had steeper cornea, induced astigmatism, and higher corneal hysteresis (CH), which implies a relationship between striae, corneal shape, and the cornea's resistance to deformation at low intraocular pressures (IOPs). BACKGROUND: Anterior corneal striae (ACS) are associated with low IOP. However, the clinical significance of ACS is unclear. Here, we aim to evaluate differences in eyes with striae compared with eyes without striae. METHODS: Adults with ACS (cases) and without ACS (controls) ≥8 weeks after glaucoma surgery with an IOP ≤10 mm Hg were enrolled. Optical coherence tomography and optical biometry were performed. CH, defined as the difference in pressure between corneal indentation and reformation in response to an air jet, was obtained by the ocular response analyzer. Hypotony maculopathy (HM) was defined as optic disc swelling, vascular tortuosity attributed to hypotony, or clinical presence of chorioretinal folds confirmed on OCT. RESULTS: One hundred sixteen eyes (76 cases, 40 controls) were included. Cases had a lower IOP compared with controls (6.5±2.3 vs. 8.5±1, P<0.0001). A 1 mm Hg increase in CH increased ACS odds [odds ratio (OR)=1.51, P=0.01]. A 1 D increase in the flattest presurgical and postsurgical corneal power increased ACS odds by 1.83 (P=0.01) and 1.41 (P=0.02), respectively. Astigmatism increased in eyes with ACS by 1.11 D (P<0.001). ACS odds were increased with every 1 minute increase in mitomycin-C duration (OR=1.58, P=0.047) and decreased with the use of topical glaucoma medication (OR=0.62, P=0.03). Visual acuity decreased from logarithm of the minimal angle of resolution 0.22 (20/33 Snellen) presurgery to 0.28 (20/38) postsurgery (P=0.008), independent of ACS. HM occurred in 19% of cases (P=0.05). A higher postsurgical CH increased HM odds (OR=1.8, P=0.003). HM predicted a 0.41 mm decrease in axial length (P<0.0001), independent of IOP. CONCLUSION: ACS were associated with a steeper cornea, induced astigmatism, and higher CH, suggesting a relationship between striae, corneal shape, and the cornea's ability to resist deformations at lower IOP. CH, HM, and axial length shortening were associated independently of IOP.

Widefield en face optical coherence tomography monitoring of the peri-venular fern-like pattern of paracentral acute middle maculopathy.

PURPOSE: To demonstrate the ability of widefield en face swept source optical coherence tomography (OCT) imaging to monitor peri-venular fern-like patterns of paracentral acute middle maculopathy (PAMM) associated with retinal arterial occlusions. OBSERVATIONS: The peri-venular fern-like pattern of PAMM was diagnosed on the 12 × 12 mm en face structural OCT images from three patients. Fluorescein angiography images were unremarkable. Over time, all three patients demonstrated significant improvement in visual acuity with resolution of their peri-venular PAMM. CONCLUSIONS: The peri-venular fern-like pattern of PAMM is usually associated with retinal vein occlusions, but we identified three cases with this pattern in eyes with presumed incomplete retinal arterial occlusions. Our cases support the ischemic cascade theory that begins within the deep capillary plexus and ascends in the retina depending on the severity of the ischemic event. Using the 12 × 12 mm en face structural OCT images, we are able to demonstrate a wider area of ischemia in PAMM compared with the traditional 6 × 6 mm scans.

Rapid initial OCT RNFL thinning is predictive of faster visual field loss during extended follow-up in glaucoma.

PURPOSE: To investigate the relationship between the rate of retinal nerve fiber layer (RNFL) loss during initial follow-up and the magnitude of associated visual field loss during an extended follow-up period. DESIGN: Retrospective cohort study. METHODS: A total of 1,150 eyes of 839 glaucoma patients extracted from the Duke Glaucoma Registry. Rates of RNFL loss were obtained from global RNFL thickness values of the first 5 optical coherence tomography (OCT) scans. Rates of visual field loss were assessed using standard automated perimetry mean deviation (SAP MD) during the entire follow-up period. Joint longitudinal mixed effects models were used to estimate rates of change. Eyes were categorized as fast, moderate or slow progressors based on rates of RNFL loss, with cutoffs of ≤-2 µm/year, -2 to -1 µm/year and ≥-1 µm/year, respectively. Univariable and multivariable regressions were completed to identify significant predictors of SAP MD loss. RESULTS: The rate of RNFL change was -0.76±0.85 µm/y during initial follow-up, which occurred over 3.7±1.5 years. 765 (66%) eyes were slow, 328 (29%) moderate, and 57 (5%) fast progressors, with rates of RNFL thinning of -0.36±0.54 µm/year, -1.34±0.25 µm/year, and -2.87±1.39 µm/year respectively. The rates of SAP MD loss among slow, moderate, and fast OCT progressors were -0.16±0.35 dB/y, -0.32±0.43 dB/y, and -0.71±0.65 dB/y respectively over the extended follow-up period of 6.1±1.9 years (P<0.001). Age, OCT progressor group, and concurrent SAP rate were all significantly associated with the overall rate of SAP MD loss in a multivariable model (all P<0.001). CONCLUSION: Rapid RNFL thinning during an initial follow-up period was predictive of concurrent and subsequent rates of visual field decline over an extended period.