This cohort study analyzes whether the rate of macular ganglion cell complex thinning is associated with the rate of central visual field loss over time in adults with glaucoma.
Key Points
Question
Is macular ganglion cell complex thinning associated with central visual field loss over time in patients with glaucoma?
Findings
In this cohort study of 202 eyes in 139 patients, more rapid macular thickness thinning during an initial follow-up period was associated with faster rates of central visual field loss over an extended period.
Meaning
These findings suggest that assessment of macular thinning was associated with central visual field loss.
Abstract
Importance
Whether rapid ganglion cell complex (GCC) thinning during an initial follow-up period is associated with rates of central visual field loss over time is unclear but important to understand because risk of glaucoma progression can help guide treatment intensity.
Objective
To investigate the association between the rate of GCC thinning during initial follow-up and the rate of central visual field loss.
Design, Setting, and Participants
This retrospective cohort study assessed patients older than 18 years with glaucoma at a tertiary glaucoma center who were followed up from June 18, 2014, to January 11, 2019. Data analysis for the current study was undertaken in March 2022.
Main Outcomes and Measures
Initial rates of GCC thinning were obtained from global GCC thickness values of the first 3 optical coherence tomography (OCT) scans. Rates of central visual field loss were assessed as the change in central (10-2) visual field mean deviation during the 4.7-year follow-up period by univariable and multivariable linear mixed-effects models. Eyes were categorized as slow (>–1 μm/y) or fast (≤–1 μm/y) progressors based on rates of GCC thinning.
Results
The cohort consisted of 202 eyes of 139 patients (mean [SD] age, 68.7 [10.0] years; 72 male [51.8%]); 44 African American patients (31.7%), 13 Asian patients (9.4%), 80 White patients (57.6%), and 2 patients who identified as other race and ethnicity (1.4%) were analyzed. The rate of GCC change was −0.56 μm/y (95% CI, −0.66 to −0.46 μm/y) during a mean initial follow-up of 1.8 years (95% CI, 1.7-2.0 years). A total of 163 eyes (80.7%) were slow OCT progressors, and 39 (19.3%) were fast OCT progressors, with rates of GCC thinning of −0.3 μm/y (95% CI, −0.4 to −0.2 μm/y) and −1.6 μm/y (−1.8 to −1.3 μm/y), respectively. The rates of 10-2 visual field mean deviation worsening among slow and fast OCT progressors were −0.10 dB/y (95% CI, −0.16 to 0.00 dB/y) and −0.34 dB/y (95% CI, −0.51 to −0.16 dB/y), respectively (difference, −0.26 dB/y; 95% CI, −0.45 to −0.07 dB/y; P = .008).
Conclusions and Relevance
In this cohort study, rapid GCC thinning during an initial follow-up period was associated with faster rates of central visual field decline. These findings support use of longitudinal macular OCT scans assisting clinical decision-making for glaucoma and also may guide possible intensification of therapy in high-risk patients.
Introduction
Glaucoma is characterized by loss of retinal ganglion cells (RGCs) and their axons that leads to characteristic changes in the optic disc with concomitant visual field (VF) damage.1 Timely detection of glaucomatous damage and monitoring of progression are essential tasks for optimal management. Patient-reported quality-of-life (QOL) outcomes appear to be more strongly correlated with central (10-2) VF damage than 24-2 VF damage.2 Therefore, glaucoma monitoring in the central macula is important for prevention of irreversible and visually disabling functional impairment.3
Macular optical coherence tomography (OCT) is an essential imaging modality for assessing central RGCs.4,5,6 Macular damage can be detected in a large proportion of patients with early perimetric glaucoma.7,8,9 Moreover, macular RGCs are among the last remaining cells in advanced glaucoma. Therefore, macular OCT imaging may be able to detect changes in RGCs and related components across the continuum of glaucoma severity.5,9,10
A key limitation of VF testing is the high test variability, which can make it difficult to detect true change over time.11,12 High variability can result in missed or delayed identification of glaucomatous progression, delayed interventions, and worse visual outcomes.12,13 In contrast to VF testing, macular OCT has excellent reproducibility and less variability over time.14,15,16 Among individuals diagnosed with glaucoma, progressive loss of neural tissue detected by OCT is believed to be associated with an increased risk of disease progression and worse visual outcomes.6 Moreover, studies have shown that OCT progression can be detected 1 to 4 years before detectable VF changes in preperimetric and perimetric glaucoma.17,18 Monitoring glaucomatous structural progression in the macula can also be detected earlier than functional (VF) changes in patients with glaucoma.7,19,20 As such, detection of OCT changes may provide an opportunity to initiate or escalate treatment to prevent irreversible VF loss. Therefore, by monitoring areas of macula that have the greatest effects on the central VF, clinicians could then monitor the central VF to detect earlier loss and determine the need for additional therapy.
Recently, it was shown that initial retinal nerve fiber layer (RNFL) thinning was associated with subsequent 24-2 VF progression.21 Owing to the sparsity and topography of the test locations for the 24-2 VF test, central functional loss may be underestimated and frequently missed with this testing strategy.22,23 Furthermore, it has been reported that the 24-2 test pattern inadequately samples OCT macular damage.24 Of note, 10-2 VF detects more progressing eyes than the 24-2 VF in patients with glaucoma with an initial parafoveal scotoma.25
The purpose of this study was to investigate the association between the rate of ganglion cell complex (GCC) thinning during an initial period of follow-up and the rate of central VF loss among patients with glaucoma. We hypothesized that fast GCC progression would be associated with fast central VF deterioration, which may justify the rationale for the use of GCC as a parameter for guiding clinical decisions for patients with glaucoma.
Methods
This retrospective cohort study included patients with primary open-angle glaucoma (POAG) and patients with suspected glaucoma who were enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS)26 and the African Descent and Glaucoma Evaluation Study (ADAGES).27,28 Written informed consent was obtained from all study participants. The University of California, San Diego, Human Subject Committee approved all protocols, and the methods described adhered to tenets of the Declaration of Helsinki.29 This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
All DIGS and ADAGES participants were assessed longitudinally according to established protocols consisting of regular follow-up visits with clinical examination, imaging, and functional tests. ADAGES and DIGS were designed with similar testing protocols, and details of the procedures used in DIGS and ADAGES have been previously published.27,28 Patients were followed up from June 18, 2014, to January 11, 2019. Data analysis for the current study was undertaken in March 2022, and all participants from the study who met the inclusion criteria were included.
All study participants underwent an annual comprehensive ophthalmologic evaluation including best-corrected visual acuity, slitlamp biomicroscopy, Goldmann applanation tonometry, dilated fundus examination, and stereoscopic optic disc photography in both eyes. Semiannual evaluations included intraocular pressure (IOP) measurement, OCT imaging, and standard automated perimetry testing. Gonioscopy and ultrasound pachymetry were completed at study entry. Sex and race and ethnicity (African American, Asian, White, and unknown [patients did not report race or ethnicity]) were determined based on self-report. Race and ethnicity were assessed in the analysis because they are known risk factors for glaucoma progression. This study included eyes with a minimum of 3 follow-up OCT scans and a maximum of 2 years’ follow-up. The rates of initial GCC thinning were then calculated based on findings of 3 OCT tests. For a comparison of the rates of initial GCC thinning with the rate of 10-2 VF mean deviation (MD) worsening, VF test results that were obtained during follow-up within 6 months from the first OCT visit were included. A minimum follow-up time of 2 years and a minimum of 5 follow-up VFs were required. Eyes with suspected glaucoma included those with elevated IOP (≥22 mm Hg) or glaucomatous-appearing optic discs (glaucomatous optic neuropathy) without presence of repeated glaucomatous VF damage. Eyes were classified as glaucomatous if they had repeated (at least 2 consecutive) abnormal VF test findings with evidence of glaucomatous optic neuropathy. Glaucomatous optic neuropathy was defined as excavation, the presence of focal thinning, notching of the neuroretinal rim, or localized or diffuse atrophy of the RNFL on the basis of masked grading of optic disc photographs by 2 graders (S.M. and T.N.) or clinical examination by a glaucoma specialist. Abnormal VF test findings were defined as a pattern SD outside the 95% normal confidence limits or a Glaucoma Hemifield Test result outside normal limits.
Inclusion criteria also included (1) age older than 18 years, (2) open angles on gonioscopy, (3) best-corrected visual acuity of 20/40 or better, and (4) refraction within ±5.0 diopters spherical and within ±3.0 diopters cylinder at study entry. Exclusion criteria included (1) history of trauma or intraocular surgery (except for uncomplicated cataract surgery or glaucoma surgery); (2) coexisting retinal disease, uveitis, or nonglaucomatous optic neuropathy; (3) other systemic or ocular diseases known to affect VF, such as pituitary lesions or demyelinating diseases; (4) substantial cognitive impairment, Parkinson disease, Alzheimer disease, dementia, or a history of stroke; and (5) axial length of 27 mm or more.
VF Testing
The Swedish interactive thresholding algorithm standard 10-2 threshold test (Humphrey Field Analyzer; Carl Zeiss Meditec) was used to obtain 10-2 VF test results. The reliability of test results was reviewed and determined by the Visual Field Assessment Center staff at the University of California, San Diego, with only reliable test results included. Visual field results were excluded if the following artifacts were presented: (1) evidence of rim and eyelid artifacts, (2) inattention or fatigue effects, and (3) VF damage caused by diseases other than glaucoma. Visual field tests with unreliable results (false positive, >33%; false negative, >33%; and fixation loss, >33%) were excluded. Visual fields were reviewed for artifacts by the University of California, San Diego, Imaging Data Evaluation and Analysis Reading Center masked to glaucoma status (healthy vs glaucomatous eye) and ancestry of patients. In cases in which the grader was unsure whether an artifact existed, a second experienced grader adjudicated.
Spectral-Domain OCT
Macula GCC thickness measurements were captured from September 2014 to November 2019 using SPECTRALIS (Heidelberg Engineering) spectral-domain OCT macula horizonal posterior pole scans. The posterior pole scan pattern of the spectral-domain OCT obtains 61 horizontal B-scans (consisting of 768 A-scans per B-scan) spanning a 30° × 25° area centered in the macula and aligned to the fovea Bruch membrane opening axis. Each B-scan is averaged 8 to 11 times to reduce speckle noise and increase image quality. Segmentation of individual retinal layers was performed using Glaucoma Module Premium Edition software (Heidelberg Engineering). The Early Treatment Diabetic Retinopathy Study30 zone macula thickness measurement was calculated automatically by the software. The mean GCC thickness measurement was calculated by averaging the sum of thickness measurement values of the RNFL, the ganglion cell layer, and the inner plexiform layer in all 9 subfields.
All images were processed and reviewed by the University of California, San Diego, Imaging Data Evaluation and Analysis Reading Center. Segmentation of macular layers was checked and corrected manually when possible. Images with noncentered scans, inaccurate segmentation that could not be fixed, or quality scores of 15 dB or less were excluded from the analysis.
Statistical Analysis
Patient and eye characteristics data were presented as mean (95% CI) and number (percentage) for continuous variables and categorical variables, respectively. A χ2 test was used to compare categorical variables. Ocular criterion among groups was analyzed using mixed-effects modeling. Models were designed with ocular measurements as the response variable and OCT progressor groups as fixed effects. The best linear unbiased prediction model was used to estimate rates of change for individual eyes. The model estimates random effects that consider the results obtained by evaluating the whole sample of eyes, placing less value on estimates captured from eyes with less consistency or large intraindividual variability, thus providing a more representative estimate. Previously, best linear unbiased prediction models were used to estimate individual rates of change measured by different instruments.31,32 Linear mixed models estimate the mean rate of change in an outcome variable using a linear function of time, and participant- and eye-specific deviations from this mean rate were introduced by random slopes. Intereye correlation was also considered in the statistical analysis. Fast (≤–1.0 μm/y) or slow (>–1.0 μm/y) OCT progressing eyes were determined based on the cutoff that was previously introduced as clinically significant progression.33 Estimated rates of VF MD worsening during the total study period in OCT progressor groups were calculated from combining the adjusted rates of VF MD worsening from the multivariable model with the mean total follow-up. The association of potential factors, such as age, mean IOP during follow-up, and any other variable in which the P value was <.10 in a univariable analysis, with rates of VF MD worsening during total follow-up was also included in the multivariable model. There were no corrections of P values made for multiple comparisons. Statistical analyses were performed using Stata, version 16.0 (StataCorp LLC). All P values were 2-sided, and P < .05 was considered to be statistically significant.
Results
A total of 202 eyes (48 with suspected glaucoma and 154 with POAG) of 139 participants were included in the analysis. The mean (SD) age of participants was 68.7 (10.0) years; 67 (48.2%) were female, and 72 (51.8%) were male. Of the patients, 44 (31.7%) were African American; 13 (9.4%), Asian; 80 (57.6%), White; and 2 (1.4%), unknown race and ethnicity. Mean baseline GCC thickness was 90.2 μm (95% CI, 88.4-92.1 μm), while mean baseline VF MD was −3.6 dB (95% CI, −4.4 to −2.9 dB). A mean of 6.3 VF visits (95% CI, 6.1-6.5 visits) was observed over the 4.7 years (95% CI, 4.5-4.8 years) of follow-up. Demographics and baseline clinical characteristics of the participants are presented in Table 1.
Table 1. Demographic and Baseline Clinical Characteristics of Study Participants.
| Characteristic | Participants (N = 139) |
|---|---|
| Age, mean (SD), y | 68.7 (10.0) |
| Sex, No. (%) | |
| Female | 67 (48.2) |
| Male | 72 (51.8) |
| Race and ethnicity, No. (%) | |
| African American | 44 (31.7) |
| Asian | 13 (9.4) |
| White | 80 (57.6) |
| Unknowna | 2 (1.4) |
| Baseline IOP, mean (95% CI), mm Hg | 14.2 (13.6 to 14.9) |
| Diagnosis, No. (%)b | |
| Glaucoma | 154 (76.2) |
| Suspected glaucoma | 48 (23.8) |
| Disease severity by baseline 24-2 VF MD, No. (%)b | |
| Early glaucoma | 153 (75.7) |
| Moderate and advanced glaucoma | 49 (24.3) |
| Baseline VF, mean (95% CI), dB | |
| 10-2 MD | −3.6 (−4.4 to −2.9) |
| 24-2 MD | −4.3 (−5.1 to −3.5) |
| 10-2 PSD | 3.7 (3.1 to 4.3) |
| 24-2 PSD | 4.8 (4.3 to 5.4) |
| Baseline GCC, mean (95% CI), μm | 90.2 (88.4 to 92.1) |
| Follow-up time, mean (95% CI), y | 4.7 (4.5 to 4.8) |
| VF visits, mean (95% CI), No. | 6.3 (6.1 to 6.5) |
Abbreviations: GCC, ganglion cell complex; IOP, intraocular pressure; MD, mean deviation; PSD, pattern SD; VF, visual field.
Patients who preferred not to report their race and ethnicity.
Data are for 202 eyes.
The rate of GCC change was −0.56 μm/y (95% CI, −0.66 to −0.46 μm/y) during the initial follow-up of 1.8 years (95% CI, 1.7-2.0 years) in all eyes. Table 2 summarizes the characteristics of eyes categorized by OCT progressor group. A total of 163 eyes (80.7%) were classified as slow OCT progressors, and 39 (19.3%) were classified as fast OCT progressors. The fast OCT progressors had a faster mean rate of GCC thinning compared with the slow progressors (−1.6 μm/y [95% CI, −1.8 to −1.3 μm/y] vs −0.3 μm/y [95% CI, −0.4 to −0.2 μm/y]; difference, −1.3 μm/y [95% CI, −1.5 to −1.0 μm/y]; P < .001). There was a lower mean IOP in the slow OCT progressor group (14.2 mm Hg; 95% CI, 13.6-14.7 mm Hg) compared with the fast OCT progressor group (15.7 mm Hg; 95% CI, 14.6-16.9 mm Hg) during follow-up (P = .04). The eFigure in the Supplement shows representative cases from the slow and fast OCT progressor groups.
Table 2. Characteristics of Eyes in Study Patients Categorized by Optical Coherence Tomography Progressor Group.
| Characteristic | Progressor group | Difference (95% CI) | P value | |
|---|---|---|---|---|
| Slow (n = 109)a | Fast (n = 30)b | |||
| Initial GCC change, mean (95% CI), μm/y | −0.3 (−0.4 to −0.2) | −1.6 (−1.8 to −1.3) | −1.3 (−1.5 to −1.0) | <.001 |
| Baseline age, mean (95% CI), per 10 y | 6.8 (6.7 to 6.9) | 7.0 (6.6 to 7.5) | 0.3 (−0.3 to 0.8) | .40 |
| Sex, No. (%) | ||||
| Female | 54 (49.5) | 18 (60.0) | NA | .31 |
| Male | 55 (54.5) | 12 (40.0) | NA | |
| Race and ethnicity, No. (%) | ||||
| African American | 37 (33.9) | 7 (23.3) | NA | .61 |
| Asian | 11 (10.1) | 2 (6.7) | NA | |
| White | 59 (54.1) | 21 (70.0) | NA | |
| Unknownc | 2 (1.8) | NA | NA | |
| Comorbidities, No. (%)d | ||||
| Hypertension | 69 (63.3) | 20 (66.7) | NA | .73 |
| Diabetes | 19 (17.4) | 4 (13.3) | NA | .59 |
| Axial length, mean (95% CI), mm | 24.4 (24.2 to 24.6) | 24.0 (23.6 to 24.5) | −0.4 (−0.8 to 0.1) | .12 |
| CCT, mean (95% CI), per 100 μm | 5.4 (5.3 to 5.4) | 5.2 (5.1 to 5.4) | −0.1 (−0.3 to 0.1) | .17 |
| Baseline IOP, mean (95% CI), mm Hg | 14.0 (13.3 to 14.6) | 15.4 (13.5 to 17.4) | 1.4 (−0.9 to 3.8) | .23 |
| IOP during follow-up, mean (95% CI), mm Hg | 14.2 (13.6 to 14.7) | 15.7 (14.6 to 16.9) | 1.6 (0.1 to 3.1) | .04 |
| Diagnosis, No. (%)e | ||||
| Glaucoma | 127 (77.9) | 12 (30.8) | NA | .25 |
| Suspected glaucoma | 36 (22.1) | 27 (69.2) | NA | |
| Disease severity by baseline 24-2 VF MD, No. (%)e | ||||
| Early glaucoma | 38 (23.3) | 11 (28.2) | NA | .52 |
| Moderate and advanced glaucoma | 125 (76.7) | 28 (71.8) | NA | |
| Baseline VF, mean (95% CI), dB | ||||
| MD | −3.6 (−4.5 to −2.7) | −3.9 (−5.2 to −2.5) | −0.3 (−2.0 to 1.5) | .76 |
| PSD | 3.7 (2.4 to 4.9) | 3.7 (3.1 to 4.4) | −0.10 (−1.6 to 1.4) | .91 |
| Follow-up time, mean (95% CI), y | 4.7 (4.5 to 4.9) | 4.4 (4.1 to 4.8) | −0.3 (−0.7 to 0.2) | .22 |
| VF visits, mean (95% CI), No. | 6.3 (6.1 to 6.5) | 6.5 (6.0 to 6.9) | 0.15 (−0.5 to 0.8) | .61 |
Abbreviations: CCT, central corneal thickness; GCC, ganglion cell complex; IOP, intraocular pressure; MD, mean deviation; NA, not applicable; PSD, pattern SD; VF, visual field.
Rate of initial GCC change (first 3 visits) was greater than −1.0 μm/y.
Rate of initial GCC change (first 3 visits) was −1.0 μm/y or less.
Patients who preferred not to report their race and ethnicity.
Comorbidities were self-reported.
Data are for 163 eyes for slow progressors and 39 eyes for fast progressors.
In the univariable model, the fast OCT progressor group showed faster 10-2 VF MD worsening compared with the slow OCT progressor group (β, −0.34 dB/y [95% CI, −0.51 to −0.16 dB/y] vs −0.10 dB/y [95% CI, −0.16 to 0.00 dB/y]; difference, −0.26 dB/y [95% CI, −0.45 to −0.07 dB/y]; P = .008). Factors associated with the rate of 10-2 VF MD change during the total follow-up are summarized in Table 3. Worse baseline 10-2 VF MD (β, 0.01; 95% CI, 0.00 to 0.03; P = .08) and African American race (β, 0.17; 95% CI, –0.01 to 0.33; P = .04) were also associated with the overall rate of 10-2 VF MD worsening in a univariable model. In the multivariable model, the fast OCT progressor group had faster rates of overall 10-2 VF MD worsening (β, −0.23; 95% CI, −0.43 to −0.03; P = .03). The Figure shows the distributions of rates of 10-2 VF MD worsening in each progressor group. Factors associated with the rate of 10-2 VF MD change during the total follow-up are summarized in eTables 1 and 2 in the Supplement for eyes with POAG and eyes with suspected glaucoma, respectively. Similar findings were found for eyes with POAG and eyes with suspected glaucoma.
Table 3. Factors Associated With the Rate of Central Visual Field Mean Deviation Change Over Time in Univariable and Multivariable Mixed Model Analyses.
| Variable | Univariable model | Multivariable model | ||
|---|---|---|---|---|
| β (95% CI) | P value | β (95% CI) | P value | |
| Age, per 10-y older | −0.00 (−0.08 to 0.07) | .93 | −0.00 (−0.08 to 0.08) | .98 |
| Female | 0.01 (−0.14 to 0.16) | .88 | NA | NA |
| African American | 0.17 (−0.01 to 0.33) | .04 | −0.23 (−0.47 to 0.01) | .06 |
| Self-reported diabetes | −0.11 (−0.31 to 0.09) | .27 | NA | NA |
| Self-reported hypertension | −0.04 (−0.20 to 0.12) | .63 | NA | NA |
| Axial length, per 1-mm longer | 0.00 (−0.06 to 0.07) | .97 | NA | NA |
| CCT, per 100-μm thinner | 0.14 (−0.03 to 0.30) | .12 | NA | NA |
| Baseline IOP, per 1–mm Hg higher | 0.00 (−0.01 to 0.02) | .77 | NA | NA |
| Mean IOP during follow-up, per 1–mm Hg higher | −0.01 (−0.03 to 0.01) | .20 | −0.02 (−0.04 to 0.01) | .18 |
| Baseline 10-2 VF MD, dB | 0.01 (−0.00 to 0.03) | .08 | 0.02 (0.00 to 0.03) | .04 |
| Follow-up period, per 1-y longer | 0.03 (−0.03 to 0.10) | .35 | NA | NA |
| No. of VF follow-up visits, per 1 visit | −0.00 (−0.05 to 0.05) | .95 | NA | NA |
| Fast vs slow OCT macula progressor group | −0.26 (−0.45 to −0.07) | .008 | −0.23 (−0.43 to −0.03) | .03 |
Abbreviations: CCT, central corneal thickness; IOP, intraocular pressure; MD, mean deviation; NA, not applicable; OCT, optical coherence tomography; VF, visual field.
Figure. Distribution of Rates in 10-2 Visual Field (VF) Mean Deviation (MD) in All Slow and Fast Progressors.
Rates of change as defined by the rates of ganglion cell complex thinning in the first 3 optical coherence tomography (OCT) tests. OCT progressor groups include slow progressors (slower than −1.0 μm/y) and fast progressors (−1.0 μm/y or faster).
Discussion
In this cohort study, a 3.4-fold greater rate of central VF change over the 4.7 years of follow-up was found for fast compared with slow macular OCT progressors. Fast progression was associated with subsequent central VF loss using only 3 macular OCT scans over a short follow-up period of less than 2 years. Given the association of central VF loss with QOL among patients with glaucoma,2 these results may have clinical importance because early identification of patients at greater risk of subsequent central VF loss can lead to timely treatment, early screening, and better monitoring of patients at risk of fast central VF loss in the future.
Rates of GCC change in our study were calculated based on only findings of the first 3 OCT tests, while rates of initial GCC thinning and the rate of central VF MD worsening used all VFs during follow-up. With this design, we were able to evaluate the structure-function correlation during the entire duration of follow-up and assess the association of initial macular OCT changes with the rate of subsequent central VF damage.
Several studies have investigated whether OCT measurements are associated with future functional deterioration.34,35 A hazard ratio of 2.0 (95% CI, 1.1-3.7) for the risk of future VF loss with each 1-μm/y faster rate of concurrent RNFL loss was found in a cohort study by Miki et al34 that used data from DIGS and ADAGES. Hazard ratios are relative parameters that do not help a clinician decide whether a specific rate of change in OCT represents risk of fast VF progression for an individual patient. Similar to the study by Miki et al,34 other studies21,36 found that fast progressors of OCT-measured RNFL thickness and OCT angiography–measured vessel density had rapid initial RNFL and initial vessel density loss, which were associated with future 24-2 VF progression. In an earlier study of OCT-measured RNFL thickness, the calculation of OCT change was based on findings of the first 5 OCT tests and rapid initial RNFL thinning was associated with VF loss.21 However, the present study highlights the potential importance of monitoring macular OCT progression over a short course of follow-up to identify patients at risk of faster central VF loss. The use of 3 OCT tests in our study allowed for risk assessment early during follow-up. Given the high reproducibility of macular OCT,16 earlier macular imaging may help to individualize and more effectively manage glaucoma, especially in those who are fast progressors.
A recent study showed that faster GCC thinning is associated with a significant decline in QOL.37 Our findings showed that eyes with fast GCC thinning detected early during follow-up had a 3.4-fold faster rate of central VF loss during the follow-up period compared with eyes that had slower GCC thinning (−0.34 dB/y vs −0.10 dB/y). Even after adjusting for confounders, the total rate of central VF loss in fast OCT progressors was approximately 2 times greater than in slow OCT progressors.
Previous studies have reported on the structure-function correlation between macular scans and central VF function.38,39,40 A weak to fair correlation between central 10-2 VF and GCC thinning in a cohort of eyes with advanced or central glaucomatous damage at baseline was found, while GCC demonstrated the highest correlation coefficients with functional measures in that study.39 In 2 other studies,38,40 the structure-function correlation was weaker at outer eccentricities (ie, more distant from the fovea). Another study41 suggested that longitudinal structure-function correlations need to be explored as a function of distance from the foveola. While previous studies investigated macular structure-function correlation, they did not provide interpretable, quantitative descriptions of how the rate of macular OCT thinning was associated with the rate of change in central VF. In the current study, initial macular thinning was associated with subsequent VF damage using simple linear approaches.
Limitations
This study has several limitations. First, patients were receiving treatment at the time of the study, and some, especially fast OCT progressors, may have experienced preferentially intensified IOP-lowering treatment. Therefore, the true rate of VF loss over time may have been underestimated. Second, the data were collected before the study design was established. Thus, we cannot exclude the possibility of selection bias, ascertainment bias, information bias, and variable follow-up and the potential effect of each of these on the interpretation of the results. Third, the severity of disease at baseline could have led to intensified treatment, subsequently leading to slower rates of VF loss in the study. Therefore, it is reasonable that our results may be conservative and that true VF loss may have been greater if there was no change in treatment. It should be noted, however, that while our data provide evidence to support treatment initiation or augmentation by a clinician in response to an early fast rate of loss in macular GCC thickness alone, additional factors need to be taken into account in decision-making, such as patient age and life expectancy.
Conclusions
The findings of this cohort study demonstrated that rapid initial GCC deterioration was associated with faster subsequent rates of central VF MD worsening. Our results support the use of macular imaging for monitoring at the time of diagnosis and for monitoring the rate of GCC thinning, which is associated with central VF progression in patients with glaucoma. This finding may be clinically relevant, especially for early detection of patients with glaucoma who are at high risk of central VF loss and for whom additional ocular hypotensive treatment should be considered.
eTable 1. Factors Contributing to the Rate of Central Visual Field Mean Deviation Change Over Time by Univariable and Multivariable Mixed Model Analysis in POAG Eyes
eTable 2. Factors Contributing to the Rate of Central Visual Field Mean Deviation Change Over Time by Univariable and Multivariable Mixed Model Analysis in Glaucoma-Suspect Eyes
eFigure. Case Examples of Fast (A) and Slow (B) OCT Progressor Group
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Associated Data
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Supplementary Materials
eTable 1. Factors Contributing to the Rate of Central Visual Field Mean Deviation Change Over Time by Univariable and Multivariable Mixed Model Analysis in POAG Eyes
eTable 2. Factors Contributing to the Rate of Central Visual Field Mean Deviation Change Over Time by Univariable and Multivariable Mixed Model Analysis in Glaucoma-Suspect Eyes
eFigure. Case Examples of Fast (A) and Slow (B) OCT Progressor Group
