The Impact of the Coronavirus Disease 2019 Pandemic on Adherence to Ocular Hypotensive Medication in Patients with Primary Open-Angle Glaucoma.

PURPOSE: Emerging evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic is disrupting health behaviors such as medication adherence. The objective of this study was to determine whether adherence to ocular hypotensive medication was affected by the pandemic and to identify factors associated with this change. DESIGN: In this cohort study, we used a controlled interrupted time series design in which the interruption was the declaration of the COVID-19 pandemic in the United States on March 13, 2020. The 300-day monitoring period, which evenly bracketed this declaration, started on October 16, 2019, and ended on August 10, 2020. PARTICIPANTS: Patients with primary open-angle glaucoma enrolled in an ongoing longitudinal National Institutes of Health-funded study initiated before the onset of the pandemic were selected if they were prescribed ocular hypotensive medication and had adherence data spanning the 300-day period. METHODS: We applied segmented regression analysis using a "slope change following a lag" impact model to obtain the adherence slopes in the periods before and after the segmentation. We compared the 2 slopes using the Davies test. MAIN OUTCOME MEASURES: The main outcome measure was daily adherence to ocular hypotensive medication, defined as the number of doses taken divided by the number of doses prescribed, expressed in percent. Adherence was measured objectively using Medication Event Monitoring System caps. We assessed the associations between change in adherence and demographic, clinical, and psychosocial factors. RESULTS: The sample included 79 patients (mean age, 71 years [standard deviation, 8 years]). Segmented regression identified a breakpoint at day 28 after the declaration of the pandemic. The slope in the period after the breakpoint (-0.04%/day) was significantly different from zero (P < 0.001) and from the slope in the period before the breakpoint (0.006%/day; P < 0.001). Mean adherence in the period before the segmentation breakpoint was significantly worse in Black patients (median, IQR: 80.6%, 36.2%) compared with White patients (median, IQR: 97.2%, 8.7%; chi-square, 15.4; P = 0.0004). A significant positive association was observed between the Connor-Davidson resilience score and the change in slope between the periods before and after the breakpoint (P = 0.002). CONCLUSIONS: Adherence to ocular hypotensive medication worsened during the COVID-19 pandemic and seems to be related to patient resilience. This collateral consequence of the pandemic may translate into vision loss that may manifest beyond its containment.

Patient and Provider Perspectives on Glaucoma Treatment Adherence: A Delphi Study in Urban Alabama.

SIGNIFICANCE: Patients with glaucoma and providers recognized perceived treatment efficacy, patient-provider relationship, psychological stress, instillation skill, good quality of life, and forgetfulness as key determinants of glaucoma adherence. This shared insight could help shape the development of clinical and behavioral interventions for addressing treatment barriers and improving adherence. PURPOSE: Despite their impact on adherence in glaucoma, sociobehavioral factors may not be adequately explored during clinical consultations. We aimed to elicit consensus between patients and providers around key determinants of adherence and hypothesized that patients would place greater emphasis on sociobehavioral factors compared with providers. METHODS: A two-round Delphi survey was used to assess treatment beliefs, barriers, facilitators, motivators, and needs among 18 patients with glaucoma and providers. In round 1, agreement with 46 statements was scored on a 5-point Likert scale (strongly disagree to strongly agree). Statements with which 80% or more of panelists agreed reached consensus and advanced to round 2, where participants were asked to prioritize them based on their importance to treatment. RESULTS: There was consensus regarding the influence of perceived treatment efficacy, good provider relationship, good quality of life, psychological stress, glaucoma knowledge, instillation skill, and forgetfulness on glaucoma adherence. For statements that failed to reach consensus, the Bonferroni-corrected Mann-Whitney U test revealed that the greatest differences between patients and providers pertained to regimen complexity (provider median, 4 [interquartile range {IQR}, 1]; patient median, 1.5 [IQR, 1]; P = .002), instillation skill (providers, 4 [IQR, 0.5]; patients, 2 [IQR, 1]; P = .001), and low motivation (providers, 3 [IQR, 2.25]; patients, 1 [IQR, 0]; P = .003). CONCLUSIONS: Although patients and providers prioritized sociobehavioral factors as key determinants of adherence, disagreement between these groups was observed in other areas. Continued juxtaposition of patient and provider perspectives could spotlight underexplored areas and guide the development of successful interventions for improving adherence.

The association between perceived cause of glaucoma and illness perceptions.

Purpose: The perceived cause of disease is an important factor that has been linked with treatment outcomes but has not been fully assessed in primary open-angle glaucoma (POAG). This study assessed the accuracy of patients' perceived cause of POAG and identified associations between accuracy, illness perceptions, medication adherence, and quality of life (QoL). Methods: The Brief Illness Perception Questionnaire (BIPQ) was used to assess illness perceptions and asked patients to rank the three most important causes of their disease in order of importance. POAG risk factors recognized by the American Academy of Ophthalmology were used to code responses as accurate or inaccurate based on the following three methods: (1) coding any reported cause, regardless of rank, (2) coding only the first-ranked cause, and (3) coding and weighting all reported causes. Medication adherence was measured electronically. QoL was measured using the Glaucoma Quality of Life questionnaire. Mann-Whitney U test was used to detect differences in illness perceptions, medication adherence, and QoL between accuracy groups. Results: A total of 97 patients identified a cause of their POAG and were included in this analysis. A higher proportion of patients reported an accurate cause (86.6% using method 1, 78.4% using method 2, and 79.4% using method 3; all p < 0.001). Mean medication adherence was 86.0% ± 17.8 and was similar across accuracy groups (all p > 0.05). Using method 2 (p = 0.045) and method 3 (p = 0.028), patients who reported an accurate cause of their POAG believed that their illness would last for a longer time compared to patients who reported an inaccurate cause. Method 3 also revealed that patients who reported an accurate cause of their POAG had lower perceived understanding of their illness (p = 0.048) compared to patients who reported an inaccurate cause. There were no differences in QoL between accuracy groups (all p > 0.05). Conclusion: This study highlights the association between perceived cause of POAG and illness perceptions related to knowledge level and POAG duration. Future studies should assess associations between perceived cause of disease and other critical dimensions of illness perception.

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.

Adherence to Ocular Hypotensive Medication in Patients With Primary Open Angle Glaucoma in Ghana.

PRCIS: There is a high rate of nonadherence to ocular hypotensive medications in a highly prevalent glaucoma setting, which warrants the attention of caregivers so as to inform their discussion of the possible barriers to adherence with their patients. PURPOSE: To assess adherence to ocular hypotensive medication objectively among glaucoma patients in Ghana and to identify factors associated with adherence. MATERIALS AND METHODS: The prospective, observational cohort study included consecutive patients with primary open angle glaucoma treated with Timolol at the Christian Eye Centre, Cape Coast, Ghana. Adherence was assessed using Medication Event Monitoring System (MEMS) for a period of 3 months. MEMS adherence was defined as the number of doses taken divided by the number of doses prescribed, expressed in percent. Patients with adherence of 75% or less were classified as nonadherent. Associations with glaucoma medication self-efficacy, eyedrop-taking behaviors, and health beliefs were also assessed. RESULTS: Of the 139 patients (mean age, 65 y [SD, 13 y]) included in the study, 107 (77.0%) were nonadherent when assessed with MEMS, compared with only 47 (33.8%) who self-reported being nonadherent. Overall, mean adherence was 48.5%±29.7. In univariate analysis, MEMS adherence was significantly associated with educational level ( χ2 =9.18, P =0.01) and the number of systemic comorbidities ( χ2 =6.03, P =0.049). CONCLUSION: Overall, mean adherence was low, and adherence was associated with educational level and number of systemic comorbidities in univariate analysis.

Whitecoat Adherence in Patients With Primary Open-Angle Glaucoma.

Purpose: Whitecoat adherence refers to improved medication adherence in the days surrounding clinic visits. This may lead to clinical measures that are not representative of those outside of clinical encounters. In glaucoma, whitecoat adherence to prescribed hypotensive therapy may lead to intraocular pressure readings within the target range, which may impact clinical decision-making. We aimed to quantify and identify factors associated with whitecoat adherence. Methods: In this cohort study, patients with primary open-angle glaucoma were selected from an ongoing longitudinal NIH-funded study if they used hypotensive eyedrops, had a clinic visit during the parent study, and had adherence data during the 28 days evenly bracketing the clinic visit. Adherence within the implementation phase was measured using Medication Event Monitoring System (MEMS) caps. Wilcoxon tests were used to compare mean adherence between the following periods: Pre14-4 (days 14 to 4 preceding the clinic visit) and Pre3-1 (days 3 to 1 preceding the visit); Post1-3 (days 1 to 3 following the clinic visit) and Post4-14 (days 4 to 14 following the visit). Analyses were performed in the full sample and in patients with optimal (≥80%, n = 49) and suboptimal adherence (<80%, n = 17). Results: Sixty-six patients were included, of which 51.5% were female. Mean age was 70.8 ± 8.1 years. In the 6 months evenly bracketing the clinic visit, mean and median adherence were 86.3% (standard deviation = 17.7) and 95.6% (interquartile range = 21.2), respectively. Overall, mean adherence increased from Pre14-4 to Pre3-1 (85.5% ± 21.2 to 88.5% ± 23.2, p = 0.01) and decreased from Post1-3 to Post4-14 (87.0 ± 23.9 to 84.9 ± 23.3, p = 0.02). In patients with optimal adherence, adherence increased from Pre14-4 to Pre3-1 (94.0 ± 11.7 to 97.7 ± 7.4, p = 0.001) and from Post1-3 to Post4-14 (95.2 ± 12.0 to 95.4 ± 5.7, p = 0.007). Whitecoat adherence was not observed in patients with suboptimal adherence. Conclusion: We documented the presence of whitecoat adherence in this cohort. Due to its potential impact on clinical outcomes and decisions, providers should remain vigilant for this phenomenon and prioritize it during patient-provider discussions.

The Usefulness of Assessing Glaucoma Progression With Postprocessed Visual Field Data.

Purpose: Data postprocessing with statistical techniques that are less sensitive to noise can be used to reduce variability in visual field (VF) series. We evaluated the detection of glaucoma progression with postprocessed VF data generated with the dynamic structure-function (DSF) model and MM-estimation robust regression (MRR). Method: The study included 118 glaucoma eyes with at least 15 visits selected from the Rotterdam dataset. The DSF and MRR models were each applied to observed mean deviation (MD) values from the first three visits (V1-3) to predict the MD at V4. MD at V5 was predicted with data from V1-4 and so on until the MD at V9 was predicted, creating two additional datasets: DSF-predicted and MRR-predicted. Simple linear regression was performed to assess progression at the ninth visit. Sensitivity was evaluated by adjusting for false-positive rates estimated from patients with stable glaucoma and by using longer follow-up series (12th and 15th visits) as a surrogate for progression. Results: For specificities of 80% to 100%, the DSF-predicted dataset had greater sensitivity than the observed and MRR-predicted dataset when positive rates were normalized with corresponding false-positive estimates. The DSF-predicted and observed datasets had similar sensitivity when the surrogate reference standard was applied. Conclusions: Without compromising specificity, the use of DSF-predicted measurements to identify progression resulted in a better or similar sensitivity compared to using existing VF data. Translational Relevance: The DSF model could be applied to postprocess existing visual field data, which could then be evaluated to identify patients at risk of progression.

Characterizing and quantifying the temporal relationship between structural and functional change in glaucoma.

PURPOSE: To characterize and quantify the temporal relationship between structural and functional change in glaucoma. METHODS: 120 eyes of 120 patients with ocular hypertension or primary open-angle glaucoma were selected from the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study. Patients had 11 visits, separated by at least 3 months over 5 to 10 years. Each visit had rim area (RA) and mean sensitivity (MS) measurements taken within a 30-day period. The structure-function (SF) relationship was summarized using conventional and modified cross-correlation functions (CCFs), which identified the strongest absolute and positive correlation, respectively. Patients were categorized in one of the following three groups: RA and MS evolved simultaneously (lag = 0), RA preceded MS (lag<0), and MS preceded RA (lag>0). Lagging regression analysis was used to examine the variations of the SF relationship within groups. RESULTS: The number of participants, mean visit lag, and mean correlation (standard deviation) were, for the conventional and modified CCFs, respectively: lag = 0 [16, 0, 0.53 (0.10) and 16, 0, 0.46 (0.11)]; lag<0 [50, -2.94, 0.51 (0.11) and 55, -3.45, 0.44 (0.12)], and lag>0 [54, 3.35, 0.53 (0.13) and 49, 3.78, 0.45 (0.12)]. A significant difference of the visit lag relation within groups was identified using lagging regression analysis (p<0.0001). CONCLUSIONS: The strongest relationship between structure and function was obtained at different visit lags in different patients. This finding also suggests that the SF relationship should be addressed at the subject level when using both measurements jointly to model glaucoma progression.

Detecting Progression in Patients With Different Clinical Presentations of Primary Open-angle Glaucoma.

PRCIS: Glaucoma progression was more frequently identified by assessing retinal fiber layer thickness than by monitoring visual field (VF) loss for different baseline classifications in primary open-angle glaucoma. PURPOSE: The aim was to compare the detection of glaucoma progression by retinal nerve fiber layer thickness (RNFLT) and VF assessments for different baseline classifications of primary open-angle glaucoma. METHODS: This study included 194 eyes from 194 patients with a minimum of 9 follow-up visits selected from the Diagnostic Innovation in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). Each eye was classified according to baseline clinical signs: ocular hypertension (n=39), glaucomatous optic neuropathy only (n=60), glaucomatous visual field loss only (GVF, n=39) and definite glaucoma (concurrent optic disc and VF defect, n=56). We assessed progression by performing simple linear regression on global and sectorial mean deviations values generated for RNFLT (RNFLT-MD) and VF data (VF-MD). The proportion of eyes identified as progressing (positive rate) by RNFLT-MD and by VF-MD were compared within each classification. RESULTS: Whereas both parameters performed similarly among glaucomatous optic neuropathy only and definite glaucoma eyes, the positive rate obtained with global RNFLT-MD was significantly greater compared with global VF-MD by 33.3% and 30.8% among ocular hypertension eyes and GVF eyes, respectively. This finding was consistent in the inferotemporal sector; however, similar positive rates were obtained for both parameters in the superotemporal sector. CONCLUSIONS: While both RNFLT and VF parameters showed comparable abilities to identify progression across the different classifications, RNFLT assessment may be better suited to monitor progression, particularly among patients with elevated intraocular pressure and those who present with only GVF defect at baseline.

Visual Field Progression in Glaucoma: Comparison Between PoPLR and ANSWERS.

Purpose: It has been suggested that the detection of visual field progression can be improved by modeling statistical properties of the data such as the increasing retest variability and the spatial correlation among visual field locations. We compared a method that models those properties, Analysis with Non-Stationary Weibull Error Regression and Spatial Enhancement (ANSWERS), against a simpler one that does not, Permutation of Pointwise Linear Regression (PoPLR). Methods: Visual field series from three independent longitudinal studies in patients with glaucoma were used to compare the positive rate of PoPLR and ANSWERS. To estimate the false-positive rate, the same visual field series were randomly re-ordered in time. The first dataset consisted of series of 7 visual fields from 101 eyes, the second consisted of series of 9 visual fields from 150 eyes, and the third consisted of series of more than 9 visual fields (17.5 on average) from 139 eyes. Results: For a statistical significance of 0.05, the false-positive rates for ANSWERS were about 3 times greater than expected at 15%, 17%, and 16%, respectively, whereas for PoPLR they were 7%, 3%, and 6%. After equating the specificities at 0.05 for both models, positive rates for ANSWERS were 16%, 25%, and 38%, whereas for PoPLR they were 12%, 33%, and 49%, or about 5% greater on average (95% confidence interval = -1% to 11%). Conclusions: Despite being simpler and less computationally demanding, PoPLR was at least as sensitive to deterioration as ANSWERS once the specificities were equated. Translational Relevance: Close control of false-positive rates is key when visual fields of patients are analyzed for change in both clinical practice and clinical trials.

Evaluation of the external validity of a joint structure-function model for monitoring glaucoma progression.

The dynamic structure-function (DSF) model was previously shown to have better prediction accuracy than ordinary least square linear regression (OLSLR) for short series of visits. The current study assessed the external validity of the DSF model by testing its performance in an independent dataset (Ocular Hypertension Treatment Study-Confocal Scanning Laser Ophthalmoscopy [OHTS-CSLO] ancillary study; N = 178 eyes), and also on different test parameters in a sample selected from the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study (DIGS/ADAGES). Each model was used to predict structure-function paired data at visits 4-7. The resulting prediction errors for both models were compared using the Wilcoxon signed-rank test. In the independent dataset, the DSF model predicted rim area and mean sensitivity paired measurements more accurately than OLSLR by 1.8-5.5% (p ≤ 0.004) from visits 4-6. Using the DIGS/ADAGES dataset, the DSF model predicted retinal nerve fiber layer thickness and mean deviation paired measurements more accurately than OLSLR by 1.2-2.5% (p ≤ 0. 007). These results demonstrate the external validity of the DSF model and provide a strong basis to develop it into a useful clinical tool.

A framework for assessing glaucoma progression using structural and functional indices jointly.

PURPOSE: While many tests and indices are available to identify glaucoma progression, using them in combinations may decrease overall specificity. The aim of this study was to develop a framework for assessing glaucoma progression using structural and functional indices jointly for a fixed specificity. METHODS: The study included 337 eyes of 207 patients with ocular hypertension or primary open-angle glaucoma selected from the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study. All patients had at least 9 visits. Each visit had retinal nerve fiber layer thickness (RNFLT) and mean sensitivity from static automated perimetry (SAP MS) measured within a one-month window. Simple linear regression was applied to assess deterioration in each index for series of 5 to 9 visits. To identify progression using the two indices jointly, marginal significance levels set at a specificity of 95% were derived for two criteria: ANY (worsening on either RNFLT or SAP MS) and ALL (worsening on both RNFLT and SAP MS). Positive rate (percentage of eyes flagged as progressing) was determined individually for each index, as well as for the ANY and ALL criteria. RESULTS: Compared to SAP MS, RNFLT had higher positive rates (15% to 45%) for all series lengths. For the joint analyses, the positive rate was on average 12% higher for the ANY criterion compared to the ALL criterion. While RNFLT-alone had comparable positive rates and time-to-detection as the ANY criterion, each uniquely identified a subset of eyes (Kappa = 0.55 to 0.75). CONCLUSIONS: This study provides a simple framework for assessing glaucoma progression with data from two tests jointly, without compromising specificity. This framework can be extended to include two or more parameters, can accommodate global or regional indices, and can eventually be used with novel parameters identified as predictive of glaucoma progression.

Functional assessment of glaucoma: Uncovering progression.

Clinicians who manage glaucoma patients carefully monitor the visual field to determine if treatments are effective or interventions are needed. Visual field tests may reflect disease progression or variability among examinations. We describe the approaches and perimetric tests used to evaluate glaucomatous visual field progression and factors that are important for identifying progression. These include stimulus size, which area of the visual field to assess (central versus peripheral), and the testing frequency, evaluating which is important to detect change early while minimizing patient testing burden. We also review the different statistical methods developed to identify change. These include trend- and event-based analyses, parametric and nonparametric tests, population-based versus individualized approaches, as well as pointwise and global analyses. We hope this information will prove useful and important to enhance the management of glaucoma patients. Overall, analysis procedures based on series of at least 5 to 6 examinations that require confirmation and persistence of changes, that are guided by the pattern and shape of the glaucomatous visual field deficits, and that are consistent with structural defects provide the best clinical performance.

Progenitor cell combination normalizes retinal vascular development in the oxygen-induced retinopathy (OIR) model.

Retinopathy of prematurity (ROP) is a disorder of the developing retina of preterm infants. ROP can lead to blindness because of abnormal angiogenesis that is the result of suspended vascular development and vaso-obliteration leading to severe retinal stress and hypoxia. We tested the hypothesis that the use of the human progenitor cell combination, bone marrow-derived CD34+ cells and vascular wall-derived endothelial colony-forming cells (ECFCs), would synergistically protect the developing retinal vasculature in a mouse model of ROP, called oxygen-induced retinopathy (OIR). CD34+ cells alone, ECFCs alone, or the combination thereof were injected intravitreally at either P5 or P12 and pups were euthanized at P17. Retinas from OIR mice injected with ECFCs or the combined treatment revealed formation of the deep vascular plexus (DVP) while still in hyperoxia, with normal-appearing connections between the superficial vascular plexus (SVP) and the DVP. In addition, the combination of cells completely prevented aberrant retinal neovascularization and was more effective anatomically and functionally at rescuing the ischemia phenotype than either cell type alone. We show that the beneficial effects of the cell combination are the result of their ability to orchestrate an acceleration of vascular development and more rapid ensheathment of pericytes on the developing vessels. Lastly, our proteomic and transcriptomic data sets reveal pathways altered by the dual cell therapy, including many involved in neuroretinal maintenance, and principal component analysis (PCA) showed that cell therapy restored OIR retinas to a state that was closely associated with age-matched normal retinas. Together, these data herein support the use of dual cell therapy as a promising preventive treatment for the development of ROP in premature infants.

Diagnostic accuracy of the Matrix 24-2 and original N-30 frequency-doubling technology tests compared with standard automated perimetry.

PURPOSE: To compare the diagnostic accuracy of the Matrix frequency-doubling technology (FDT) 24-2, first-generation FDT N-30 (FDT N-30), and standard automated perimetry (SAP) tests of visual function. METHODS: One eye of each of 85 glaucoma patients and 81 healthy controls from the Diagnostic Innovations in Glaucoma Study was included. Evidence of glaucomatous optic neuropathy on stereophotographs was used to classify the eyes. Matrix FDT 24-2, first-generation FDT N-30, and SAP-SITA 24-2 tests were performed on all participants within 3 months. Receiver operating characteristic (ROC) curves were generated and used to determine sensitivity levels at 80% and 90% specificity for mean deviation (MD), pattern standard deviation (PSD), number of total deviation (TD), and pattern deviation (PD) points triggered at less than 5% and 1%. The tests were compared using the best parameter for each test (that with the highest area under the ROC curve) and with the PSD. RESULTS: The best parameters were MD for SAP (0.680), PSD for FDT N-30 (0.733), and number of TD less than 5% points for FDT 24-2 (0.774). Using the best parameter, the area under the ROC curve was significantly larger for FDT 24-2 than for SAP (P = 0.01). No statistically significant differences were observed between SAP and FDT N-30 (P = 0.21) and FDT N-30 and FDT 24-2 (P = 0.26). Similar results were obtained when the PSD was used to compare the tests, with the exception that the area under the ROC curve for the FDT N-30 test (0.733) was significantly larger than that of the SAP-SITA (0.641; P = 0.03). CONCLUSIONS: The performance of the Matrix FDT 24-2 was similar to that of the first-generation FDT N-30. The Matrix FDT 24-2 test was consistently better than SAP at discriminating between healthy and glaucomatous eyes. Further studies are needed to evaluate the ability of the Matrix FDT 24-2 to monitor glaucoma progression.

Associations between structure and function are different in healthy and glaucomatous eyes.

PURPOSE: To assess if there are differences in the structure-function associations between healthy and glaucomatous eyes. METHODS: Structure-function associations were assessed in healthy and glaucomatous eyes in three datasets, globally and in the six sectors of the optic nerve head. Structural parameters included rim area (RA) and retinal nerve fiber layer thickness (RNFLT). Functional parameters included unweighted mean of sensitivity thresholds (MS) and unweighted mean of total deviation values (MD), assessed with standard automated perimetry, short-wavelength automated perimetry, frequency-doubling technology perimetry, or contrast sensitivity perimetry. All structural and functional parameters were expressed as percent of mean normal. SF associations were assessed with correlation analyses (Pearson, Spearman and Kendall). We also assessed the SF associations with linear regression analyses: the generalized estimating equation (GEE) was used to adjust for inter-eye correlations and ordinary least squares (OLS) linear models were used when these adjustments were not necessary. We applied Bonferroni corrections to adjust for the impact of multiple comparisons. RESULTS: Overall, none of the Pearson correlations tested in healthy eyes were significant (correlations ranged from -0.17 to 0.37), whereas 77% of the correlations tested in glaucomatous eyes were significant (correlations ranged from 0.01 to 0.79). Similarly, none of the slopes obtained with GEE and OLS were significant in healthy eyes (slopes ranged from -0.30 to 0.87), whereas 82% of the slopes obtained in glaucomatous eyes were significant (slopes ranged from 0.02 to 1.38). CONCLUSIONS: Significant associations between structure and function were consistently observed in glaucomatous eyes, but not in healthy eyes. These differences in association should be considered in the design of structure-function models for progression.

Prediction Accuracy of the Dynamic Structure-Function Model for Glaucoma Progression Using Contrast Sensitivity Perimetry and Confocal Scanning Laser Ophthalmoscopy.

PURPOSE: The purpose of this study was to determine whether combining a structural measure with contrast sensitivity perimetry (CSP), which has lower test-retest variability than static automated perimetry (SAP), reduces prediction error with 2 models of glaucoma progression. METHODS: In this retrospective analysis, eyes with 5 visits with rim area (RA), SAP, and CSP measures were selected from 2 datasets. Twenty-six eyes with open-angle glaucoma were included in the analyses. For CSP and SAP, mean sensitivity (MS) was obtained by converting the sensitivity values at each location from decibel (SAP) or log units (CSP) to linear units, and then averaging all values. MS and RA values were expressed as percent of mean normal based on independent normative data. Data from the first 3 and 4 visits were used to calculate errors in prediction for the fourth and fifth visits, respectively. Prediction errors were obtained for simple linear regression and the dynamic structure-function (DSF) model. RESULTS: With linear regression, the median prediction errors ranged from 6% to 17% when SAP MS and RA were used and from 9% to 17% when CSP MS and RA were used. With the DSF model, the median prediction errors ranged from 6% to 11% when SAP MS and RA were used and from 7% to 16% when CSP MS and RA were used. CONCLUSIONS: The DSF model had consistently lower prediction errors than simple linear regression. The lower test-retest variability of CSP in glaucomatous defects did not, however, result in lower prediction error.

The effect of disc size and severity of disease on the diagnostic accuracy of the Heidelberg Retina Tomograph Glaucoma Probability Score.

PURPOSE: To compare the effect of disc size and disease severity on the Heidelberg Retina Tomograph (HRT) Glaucoma Probability Score (GPS) and the Moorfields Regression Analysis (MRA) for discriminating between glaucomatous and healthy eyes. METHODS: Ninety-nine eyes with repeatable standard automated perimetry results showing glaucomatous damage and 62 normal eyes were included from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). The severity of glaucomatous visual field defects ranged from early to severe (average [95% CI] pattern standard deviation [PSD] was 5.7 [5.0-6.5] dB). The GPS (HRTII ver. 3.0; Heidelberg Engineering, Heidelberg, Germany) utilizes two measures of peripapillary retinal nerve fiber layer shape (horizontal and vertical retinal nerve fiber layer curvature) and three measures of optic nerve head shape (cup depth, rim steepness, and cup size) as input into a relevance vector machine learning classifier that estimates a probability of having glaucoma. The MRA compares measured rim area with predicted rim area adjusted for disc size to categorize eyes as outside normal limits, borderline, or within normal limits. The effect of disc size and severity of disease on the diagnostic accuracy of both GPS and MRA was evaluated using the generalized estimating equation marginal logistic regression analysis. RESULTS: Using the manufacturers' suggested cutoffs for GPS global classification (>64% as outside normal limits), the sensitivity and specificity (95% CI) were 71.7% (62.2%-79.7%) and 82.3% (71.0%-89.8%), respectively. The sensitivity and specificity (95% CI) of the MRA result were 66.7% (58.0%-76.1%) and 88.7% (78.5%-94.34%), respectively. Likelihood ratios for regional GPS and MRA results outside normal limits ranged from 4.0 to 10.0, and 6.0 to infinity, respectively. Disc size and severity of disease were significantly associated with the sensitivity of both GPS and MRA. CONCLUSIONS: GPS tended to have higher sensitivities and somewhat lower specificities and lower likelihood ratios than MRA. These results suggest that in this population, GPS and MRA differentiate between glaucomatous and healthy eyes with good sensitivity and specificity. In addition, the likelihood ratios suggest that GPS may be most useful for confirming a normal disc, whereas MRA may be most helpful in confirming a suspicion of glaucoma. Larger disc size and more severe field loss were associated with improved diagnostic accuracy for both GPS and MRA.

The impact of the perimetric measurement scale, sample composition, and statistical method on the structure-function relationship in glaucoma.

PURPOSE: To investigate the impact of perimetric measurement scales, sample composition, and 2 statistical methods on the structure-function relationship in glaucoma. METHODS: Three hundred eighty-five eyes of 385 participants, covering the full spectrum of the disease from healthy to advanced glaucoma, were tested with the Heidelberg Retina Tomograph and standard automated perimetry (Swedish Interactive Thresholding Algorithm) within a 6-month period. The associations (R) between neuroretinal rim area and perimetric data expressed in logarithmic (dB) and linear (1/Lambert) units were measured for linear and curvilinear (quadratic and logarithmic) models. The best-fit model resulting from 2 statistical analyses (chi coefficient and analysis of the residuals) were compared in the visual field areas corresponding to the 6 Heidelberg Retina Tomograph sectors and in the central visual field. These analyses were performed on the complete sample and on a subset of the study population composed only of healthy controls and patients with definite glaucoma. RESULTS: The R values ranged from 0.01 to 0.32 with the strongest associations in the supero-temporal and infero-temporal optic disc regions. When perimetric data were expressed in dB units, the curvilinear models generally explained more variance than the linear model. When perimetric data were expressed in 1/Lambert units, differences were observed between the 2 statistical and subgroup analyses. CONCLUSIONS: The perimetric measurement scale is one of many factors influencing the structure-function relationship. It is also influenced by the composition of the sample and by the statistical method of analysis. Expressing perimetric data in linear units does not always translate into linear structure-function relationships.

Comparison of matrix frequency-doubling technology perimetry and standard automated perimetry in monitoring the development of visual field defects for glaucoma suspect eyes.

BACKGROUND: Perimetry is indispensable for the clinical management of glaucoma suspects. Our goal is to compare the performance of standard automated perimetry (SAP) and Matrix frequency-doubling technology (FDT) perimetry in monitoring the development of visual field (VF) defects in glaucoma suspect eyes. METHODS: Longitudinal data of paired SAP and FDT from 221 eyes of 155 glaucoma suspects enrolled in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study were included. All eyes had glaucomatous optic neuropathy or ocular hypertension, but normal SAP and FDT results at baseline. The development of glaucomatous VF defects was defined as the presence of a cluster of ≥ 3 (less conservative) or ≥ 4 (more conservative) locations confirmed on ≥ 2 additional consecutive tests. Risk factors for the development of VF defects were analyzed by COX proportional hazard models. After conversion into common logarithmic units, the rates of change of global VF indices were fitted with linear mixed models. RESULTS: FDT detected more eyes that developed VF defects than SAP using the less conservative criterion, and no significant difference was observed using the more conservative criterion. For those eyes detected by both SAP and FDT, FDT detected the development of VF defects either earlier than SAP or simultaneously in most cases. Baseline structural measurements were not significantly associated with an increased risk for the development of glaucomatous VF defects on either SAP or FDT. Older age was significantly associated with the development of VF defects on FDT but not on SAP. Both SAP and FDT detected a progressing worsening trend of pattern standard deviation over time with a similar rate of change between these test types. CONCLUSIONS: Matrix FDT would be useful to monitor the onset of VF defects in glaucoma suspects and may outperform SAP in the early stage of glaucomatous VF damage.