Differential Impact of Central and Global Visual Field Progression on Quality of Life in Glaucoma





Purpose


To determine the impact of progression of central visual field (VF) and global VF on vision-related quality of life (VRQOL).


Design


Retrospective cohort study.


Methods


This study included 364 eyes of 235 primary open-angle glaucoma participants who had at least five 24-2 VF tests over a minimum of 2-year follow-up. The slopes of global mean deviation (MD) and central mean total deviation (MTD 10 ) (12 test points within the central 10° of 24-2) were calculated. Analyses were conducted using different slope thresholds to define VF-based progression, and mean composite National Eye Institute Visual Function Questionnaire Rasch-calibrated scores associated with these progression thresholds were quantified using linear mixed-effects models.


Results


The baseline 24-2 VF MD of all participants was –5.6 (95% CI –6.4, –4.9) decibels (dB). At baseline, eyes with MTD 10 progression had significantly worse 24-2 VF MD compared to those without MTD 10 progression. When fast progression was defined as MTD 10 slope <–0.50 dB/y, fast progressors had a mean baseline 24-2 MD of –9.71 dB (95% CI –11.89, –7.53) compared to –5.24 dB (95% CI –6.02, –4.46) in slow progressors ( P < .001). Eyes exhibiting MTD 10 progression consistently displayed worse mean composite VRQOL scores across various thresholds compared to global MD. Notably, a similar level of VRQOL impairment was observed at a lower threshold for MTD 10 compared to MD, consistent across all glaucoma severity groups. In the overall cohort, eyes progressing at a rate of –0.5 dB/y or faster for MTD 10 had a mean composite VRQOL score comparable to those progressing at –1.0 dB/y or faster for global MD.


Conclusions


Central VF change had a greater impact on VRQOL compared to global VF change. Conventional assessments based on global MD may underestimate the effect of central VF changes. Refining progression detection strategies to include central VF is necessary to better reflect changes in patient-centered outcomes like VRQOL.


INTRODUCTION


Glaucoma, a chronic, progressive optic neuropathy, is characterized by the gradual loss of visual function and is a major cause of blindness worldwide. , Vision loss from glaucoma significantly diminishes quality of life. Many patients experience difficulties with reading, walking, driving, preparing meals, and taking medications, among other activities, while also facing social withdrawal, depression, and fear of blindness.


The National Eye Institute Visual Function Questionnaire (NEI-VFQ) was designed to assess the impact of ocular disease on vision-related quality of life (VRQOL). , Previous studies have demonstrated that lower NEI-VFQ scores significantly correlate with the severity of glaucomatous visual field (VF) deterioration. Even mild VF damage has been shown to adversely affect VRQOL in glaucoma patients, and faster VF loss has been associated with worse VRQOL outcomes. , , This close association between VF loss and VRQOL emphasizes the importance of clinically monitoring VF changes, especially within the central region, as an individual’s subjective experiences and objective abilities to perform daily tasks and maintain personal safety heavily depend on central vision. ,


Estimating the rates of functional VF loss is crucial for glaucoma management, as it enables clinicians to identify patients experiencing rapid deterioration who may require timely therapeutic intervention. In clinical practice, a decline exceeding –1.0 decibels (dB) per year in the mean deviation (MD) of the entire 24-2 VF test typically is considered indicative of fast progression. However, an equivalent magnitude of central VF change can lead to a more pronounced functional impairment, given the strong association between central visual function and VRQOL. , , , Such changes are particularly concerning as so many patients with glaucoma are at risk for vision loss.


For example, approximately 1 in 8 eyes with glaucoma under routine care demonstrate fast progression based on global MD values (<–1.0 dB/y) and nearly 1 in 3 eyes show a decline of <–0.5 dB/y centrally. Despite these findings, there is currently no universally accepted definition for fast progression in the central VF.


Therefore, our study aimed to evaluate and define the threshold rate indicative of fast progression within the central VF by assessing the progression rate in the central VF region that results in a comparable level of VRQOL to that seen with global MD. Establishing such a rate could provide valuable insights into identifying fast progression in the central region that may detrimentally impact patients’ quality of life.


METHODS


PARTICIPANTS


This retrospective longitudinal cohort study included primary open-angle glaucoma (POAG) patients examined in two prospective observational studies—the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). Both studies have the same protocol for tests relevant to this report. The multicenter ADAGES collaboration includes the Hamilton Glaucoma Center at the Department of Ophthalmology, University of California, San Diego (UCSD) (data coordinating center), Edward S. Harkness Eye Institute at Columbia University Irving Medical Center, and the Department of Ophthalmology at University of Alabama Birmingham. All participants from the DIGS and ADAGES study who met the inclusion criteria described below were enrolled in the current study. The institutional review boards at all sites approved the study methodology, which adheres to the tenets of the Declaration of Helsinki and to the Health Insurance Portability and Accountability Act. Written informed consent was obtained from all participants.


INCLUSION AND EXCLUSION CRITERIA


Inclusion criteria for DIGS/ADAGES were: (1) age ≥18 years; (2) best-corrected visual acuity of 20/40 or better at study entry; and (3) open angles on gonioscopy. Routine examinations of DIGS/ADAGES included: (1) gonioscopy and ultrasound pachymetry at the first visit; (2) semiannual examination of Goldmann applanation tonometry (for intraocular pressure measurement) and VF; and (3) annual comprehensive ophthalmic examination with dilated fundus examination, slit-lamp biomicroscopy, best-corrected visual acuity, and stereoscopic optic disc photography. Relevant clinical information, such as demographics and systemic medical history, was also collected. Only eyes that had five or more reliable 24-2 VF tests over a minimum of 2-year follow-up were included in the current study.


Participants with the following conditions were excluded: (1) axial length ≥27 mm; (2) uveitis; (3) history of trauma; (4) nonglaucomatous optic neuropathy; (5) coexisting significant retinal disease; (6) history of Parkinson’s disease, clinical dementia, or stroke. POAG was defined as the presence of open angles on gonioscopy and the absence of secondary causes of glaucoma. To include in the study, these eyes were also required to have repeatable and reliable (fixation losses and false-negative results 33% and false-positive results 15%) glaucomatous VF damage defined as a pattern standard deviation outside 95% of normal limits or glaucoma hemifield test results outside normal limits with or without glaucomatous optic neuropathy by stereoscopic photography assessment (ie, the presence of focal thinning, notching, or localized or diffuse atrophy of the circumpapillary retinal nerve fiber layer on the basis of masked grading of optic disc photographs by two graders.


VISUAL FIELD


This study included individuals who underwent VF testing using the Swedish Interactive Thresholding Algorithm Standard 24-2 strategy on the Humphrey Field Analyzer (Carl Zeiss Meditec, Inc.). Only 24-2 VF tests with <33% fixation loss, <33% false-negative, and <15% false-positive errors were considered reliable and included in the analyses. A total of 63 eyes (0.97%) were excluded based on the <33% fixation loss criterion, 2 eyes (0.03%) based on the <33% false-negative criterion, and 85 eyes (1.3%) based on the <15% false-positive criterion. VF images were reviewed by experienced graders at the UCSD Visual Field Assessment Center, and eyelid or rim artifacts, fatigue or learning effects, inappropriate fixation, or evidence that the VF results were caused by a disease other than glaucoma (eg, homonymous hemianopia) or inattention were excluded. Eyes with glaucoma were stratified into three groups based on the severity of VF damage at baseline: early for better than –6 dB, moderate for between –6 and –12 dB, and advanced for worse than –12 dB.


MTD 10 in dB was calculated as the logarithm of the averaged antilogs of the individual sensitivity thresholds for the 12 test locations within the central 10° VF region.


RASCH ANALYSIS OF NEI-VFQ


The VRQOL was assessed using the 25-item NEI-VFQ. This questionnaire is designed to evaluate dimensions of self-reported vision-related health that are pertinent to patients with chronic eye conditions, including glaucoma. , The NEI-VFQ contains 25 questions related to vision, divided into 11 subscales, along with an additional single-item general health question. The 11 subscales include general vision, ocular pain, difficulties with near and distance vision activities, limitations in peripheral and color vision, social functioning, driving challenges, vision-related mental health symptoms, role limitations, and dependency. Each subscale comprises 1 to 4 items. Rasch analysis places item difficulty and individual ability on a logit scale. The disability scores from the NEI-VFQ were linearly rescaled from 0 to 100, where a score of 50 corresponds to 50% of the highest disability level, with higher scores indicating worse visual function and well-being. , Rasch analysis utilized Andrich rating scale models to estimate item difficulty, participant ability, and category thresholds for each response category. , Although the method of successive dichotomizations has been reported to yield valid person measures and is not affected by disordered thresholds, both Andrich and method of successive dichotomizations models produced similar results in our analysis ( Figure 1 ). Therefore, the Andrich model was used in the present study to maintain consistency with our prior work. Items related to mental health symptoms, role limitations, and dependency were excluded, as previous research indicated these items are part of a separate socioemotional dimension not directly tied to visual functioning. NEI-VFQ questionnaires were completed within 1 year of the last VF test.




FIGURE 1


Smoothing spline plot displaying the mean composite scores using Andrich model and MSD across varying levels of progression thresholds, using the ordinary least squares slope for each central mean total deviation and global mean deviation to define progression in the overall cohort. MD = mean deviation from the entire 24-2 visual field test; MSD = method of successive dichotomizations; MTD 10 = mean total deviation of the 12 test locations within the central 10° region of the 24-2 visual field test; VF = visual field.


STATISTICAL ANALYSIS


Clinical and demographic characteristics are presented as mean (95% confidence interval) and count (percentage) for continuous and categorical variables, respectively. Comparisons of cohort characteristics were applied at the disease severity stratification level. Patient-specific categorical variables were compared using Fisher’s Exact test, while continuous variables were compared using one-way analysis of variance (ANOVA). As both eyes (if eligible) from individual subjects were included in the study, the eye-level characteristics were compared between groups using mixed-effects models and mixed-design ANOVA to account for the correlation between eyes within subjects. Comparisons of cross-sectional and longitudinal continuous eye-level characteristics were evaluated using linear mixed-effects models, which were fitted with a random intercept to adjust for between-subject variability and allow for repeated measures within subjects. To ensure the appropriate application of one-way ANOVA, mixed-design ANOVA, and linear mixed-effects modeling, normality of residuals was assessed using Q-Q plots and histograms, and homoscedasticity was evaluated using residual plots as well as Levene’s test before applying one-way ANOVA. Additionally, Cook’s distance was used to locate outliers in our data; however, no influential observations were located.


MD and MTD 10 progression rates were calculated separately for each individual eye across the full study follow-up period, in dB per year (dB/y), using ordinary least squares (OLS) regression. To investigate the relationship between VF progression and VRQOL, varying thresholds of VF progression were defined (ie, worse than [≤] 0.00 dB/y, ≤–0.05 dB/y, ≤–0.10 dB/y, ≤–0.15 dB/y, up to ≤–1.0 dB/y). At each threshold, VRQOL mean scores were calculated using the composite NEI-VFQ Rasch-calibrated scores among eyes that met each respective progression threshold for MD and MTD 10 , respectively. Linear mixed-effects models were utilized to estimate the mean VRQOL scores at each progression threshold, with random intercepts to account for between-subject variability. The aim of our study was to identify the threshold indicative of fast progression within the central VF, determined by the progression threshold that resulted in a comparable level of VRQOL to that observed with global MD.


A sensitivity analysis followed in which mean VRQOL scores were calculated across each threshold for MD and MTD 10 across early, moderate, and advanced glaucoma eyes separately. Smoothing splines were used to visualize the mean composite VRQOL scores across varying levels of progression thresholds in each cohort (overall, early glaucoma, moderate glaucoma, and advanced glaucoma). All statistical analyses were performed using the R programming language for statistical computing, Version 4.2.3 (R Foundation for Statistical Computing, Vienna, Austria) and Stata 18.0 (StataCorp LLC). Two-sided P values less than .05 were considered statistically significant.


RESULTS


This study included 364 eyes of 235 POAG participants who underwent a mean of 17.3 (95% CI 16.3-18.3) VF tests over a mean follow-up duration of 13.4 (95% CI 12.8-13.9) years. The mean age of study participants was 60.4 (95% CI 59.1-61.7) years. Two hundred fifty eyes of 166 participants had early glaucoma with a mean baseline (VF MD: –2.1 [95% CI –2.5, –1.8]) dB, 53 eyes of 33 participants had moderate glaucoma (baseline VF MD: –8.9 [95% CI –9.7, –8.2]) dB and 61 eyes of 36 participants had advanced glaucoma (baseline VF MD: –17.5 [95% CI –18.2, –16.8]) dB. The overall baseline 24-2 VF MD of all participants was (–5.6 [–6.4, –4.9]) dB. At baseline, eyes with MTD 10 progression had significantly worse 24-2 VF MD compared to those without MTD 10 progression. When fast progression was defined as MTD 10 slope <–0.50 dB/y, fast progressors had a mean baseline 24-2 MD of –9.71 dB (95% CI –11.89, –7.53) compared to –5.24 dB (95% CI –6.02, –4.46) in slow progressors ( P < .001) (data not shown). At baseline, 199 eyes (54.7%) had central VF defects, defined as having any of the 12 central points on the 24-2 VF pattern deviation map depressed at the <0.5% level compared to the normative database. A detailed summary of the demographic and clinical characteristics of the study participants in the overall cohort and according to the baseline disease severity groups is shown in Table .



TABLE

Demographic and Clinical Characteristics of the Study Participants in the Overall Cohort and in Eyes with Early, Moderate, and Advanced Glaucoma Severity at Baseline

































































































































































































Characteristic Overall Early (MD ≥ –6 dB) Moderate (−6 dB > MD ≥ −12 dB) Advanced (MD > –12 dB) P Value a
Participant-specific
No. of participants (eyes) 235 (364) 166 (250) 33 (53) 36 (61)
Age, y 60.4 (59.1, 61.7) 59.9 (58.5, 61.4) 63.6 (59.7, 67.4) 59.6 (55.7, 63.5) .064
Female, No. 127 (54.0%) 99 (59.6%) 14 (42.4%) 14 (38.9%) .029
Race, No. (%)
African Americans 94 (40.0%) 70 (42.2%) 7 (21.2%) 17 (47.2%) .009
White 136 (57.9%) 95 (57.2%) 24 (72.7%) 17 (47.2%)
Asian 3 (1.3%) 1 (0.6%) 1 (3.0%) 1 (2.8%)
Alaskan Native 1 (0.4%) 0 (0.0%) 1 (3.0%) 0 (0.0%)
Unknown 1 (0.4%) 0 (0.0%) 0 (0.0%) 1 (2.8%)
Self-reported hypertension 25 (10.6%) 19 (11.4%) 4 (12.1%) 2 (5.6%) .605
Self-reported diabetes 3 (1.3%) 3 (1.8%) 0 (0.0%) 0 (0.0%) .999
Eye-specific
Follow-up duration, y 13.4 (12.8, 13.9) 13.4 (12.8, 14.0) 13.4 (12.7, 14.2) 13.1 (12.4, 13.9) .651
No. of VF visits 17.3 (16.3, 18.3) 17.7 (16.6, 18.7) 17.3 (15.9, 18.7) 15.7 (14.3, 17.1) .005
Axial length, mm 24.2 (24.1, 24.4) 24.2 (24.1, 24.4) 24.2 (24.0, 24.4) 24.2 (24.0, 24.4) .988
CCT, µm 540.2 (535.2, 545.3) 541.5 (536.3, 546.6) 538.2 (531.8, 544.7) 536.4 (529.9, 542.8) .076
IOP parameters, mm Hg
Baseline IOP 16.9 (16.2, 17.5) 17.2 (16.5, 17.9) 16.6 (15.3, 18.0) 15.7 (14.4, 17.0) .090
Mean IOP during follow-up 14.6 (14.2, 15.0) 15.2 (14.8, 15.7) 14.1 (13.3, 14.9) 12.5 (11.7, 13.2) <.001
Baseline global VF MD, dB –5.6 (–6.4, –4.9) –2.1 (–2.5, –1.8) –8.9 (–9.7, –8.2) –17.5 (–18.2, –16.8) <.001
Baseline MTD 10 , dB –2.93 (–3.46, –2.39) –1.37 (–1.80, –0.94) –3.84 (–4.62, –3.06) –8.72 (–9.51, –7.94) <.001
Rates of MD change, dB/y –0.3 (–0.3, –0.2) –0.3 (–0.3, –0.2) –0.3 (–0.4, –0.2) –0.2 (–0.3, –0.1) .336
Rates of MTD 10 change, dB/y –0.2 (–0.2, –0.1) –0.1 (–0.2, –0.1) –0.2 (–0.3, –0.1) –0.2 (–0.3, –0.2) .008
Mean Composite NEI-VFQ Rasch-calibrated scores b 46.8 (43.9, 49.7) 42.9 (39.5, 46.2) 54.3 (46.9, 61.7) 58.2 (50.6, 65.8) <.001
Intervening cataract surgery during follow-up, No. 166 (45.6%) 124 (49.6%) 22 (41.5%) 20 (32.8%) .249

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Jul 26, 2025 | Posted by in CARDIOLOGY | Comments Off on Differential Impact of Central and Global Visual Field Progression on Quality of Life in Glaucoma

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