What is the Optimal Frequency of Visual Field Testing to Detect Rapid Progression Among Hypertensive Eyes?

PRCIS: We evaluated 16,351 visual field (VF) tests from Ocular Hypertension Treatment Study (OHTS) database and showed that more frequent testing resulted in a shorter time to detect glaucoma progression, with the best trade-off being the 6-month intervals for high-risk and 12 months for low-risk patients. PURPOSE: To investigate the effect of different testing intervals on time to detect visual field progression in eyes with ocular hypertension. METHODS: A total of 16,351 reliable 30-2 VF tests from 1575 eyes of the OHTS-1 observation arm with a mean (95% CI) follow-up of 4.8 (4.7-4.8) years were analyzed. Computer simulations (n = 10,000 eyes) based on mean deviation values and the residuals of risk groups (according to their baseline 5 y risk of developing primary open angle glaucoma: low, medium, and high risk) were performed to estimate time to detect progression with testing intervals of 4, 6, 12, and 24 months using linear regression. The time to detect VF progression ( P < 5%) at 80% power was calculated based on the mean deviation slope of -0.42 dB/year. We assessed the time to detect a -3 dB loss as an estimate of clinically meaningful perimetric loss. RESULTS: At 80% power, based on the progression of -0.42 dB/year, the best trade-off to detect significant rates of VF change to clinically meaningful perimetric loss in high, medium, and low-risk patients was 6, 6, and 12-month intervals, respectively. CONCLUSION: Given the importance of not missing the conversion to glaucoma, the frequency of testing used in OHTS (6 mo) was optimal for the detection of progression in high-risk patients. Low-risk patients could potentially be tested every 12 months to optimize resource utilization.

Frequency of Optical Coherence Tomography Testing to Detect Progression in Glaucoma.

PRCIS: With high specificity and less variability than perimetry, more frequent testing resulted in shorter time to detect progression, though a 6-month testing interval provides a reasonable trade-off for following glaucoma patients using optical coherence tomography (OCT). PURPOSE: To investigate the time to detect progression in glaucomatous eyes using different OCT test intervals. MATERIALS AND METHODS: Participants with manifest glaucoma from the African Descent and Glaucoma Evaluation Study (ADAGES), a multicenter, prospective, observational cohort study, were included. A total of 2699 OCT tests from 171 glaucomatous and 149 normal eyes of 182 participants, with at least 5 tests and 2 years of follow-up, were analyzed. Computer simulations (n=10,000 eyes) were performed to estimate time to detect progression of global circumpapillary retinal nerve fiber layer thickness (cpRNFL) measured with OCT tests. Simulations were based on different testing paradigms (every 4, 6, 12, and 24 mo) and different rates of change (µm/year). Time to detect significant progression ( P <0.05) at 80% and 90% power were calculated for each paradigm and rate of cpRNFL change. RESULTS: As expected, more frequent testing resulted in shorter time to detect progression. Although there was clear disadvantage for testing at intervals of 24 versus 12 months (~22.4% time [25 mo] increase in time to progression detection) and when testing 12 versus 6 months (~22.1% time [20 mo] increase), the improved time to detect progression was less pronounced when comparing 6 versus 4 months (~11.5% time [10 mo] reduction). CONCLUSION: With high specificity and less variability than perimetry, a 6-month testing interval provides a reasonable trade-off for following glaucoma patients using OCT.

The 24-2 Visual Field Guided Progression Analysis Can Miss the Progression of Glaucomatous Damage of the Macula Seen Using OCT.

PURPOSE: To better understand the efficacy of the 24-2 guided progression analysis (GPA) in the detection of progression in eyes with early glaucoma (i.e., 24-2 mean deviation [MD] better than -6 dB) by comparing 24-2 GPA with a reference standard (RS) based on a combination of OCT and 24-2 and 10-2 visual field (VF) information. DESIGN: Cross-sectional study. PARTICIPANTS: Ninety-nine eyes from 99 individuals, including 70 suspected or early glaucomatous eyes (24-2 MD better than -6 dB) and 29 healthy controls (HCs). METHODS: All the eyes had at least 4 OCT and VF test dates over a period that ranged from 12 to 59 months. The 24-2 VF tests included 2 baseline tests and at least 2 follow-up tests. The 2 baseline tests were performed within an average of 5.6 days (median, 7 days), and the last follow-up test was performed at least 1 year after the first baseline visit. MAIN OUTCOME MEASURES: A commercial 24-2 GPA software, with default settings, characterized the eyes as having "likely progression" (LP) or "possible progression" (PP); both were considered "progressing" for this analysis. For RS, 3 authors graded progression using strict criteria and a combination of a custom OCT progression report and commercial 24-2 and 10-2 GPA reports for the same test dates as GPA. RESULTS: The reference standard identified 10 (14%) of the 70 patient eyes and none of the HC eyes as having progression. The 24-2 guided progression analysis identified 13 of the 70 patient eyes as having progression (PP or LP). However, it correctly classified only 4 (40%) of the 10 RS progressors. All 6 of the RS progressors missed by the 24-2 GPA showed progression in the macula. In addition, the 24-2 GPA identified 2 of the 29 HC eyes as progressors and 9 patient eyes without progression based on the RS. CONCLUSIONS: In eyes with early glaucoma (i.e., 24-2 MD, > -6 dB) in this study, the 24-2 GPA missed progression seen using OCT and exhibited a relatively high rate of false positives. Furthermore, the region progressing typically included the macula. The results suggest that including OCT and/or 10-2 VFs should improve the detection of progression.

Glaucomatous Visual Field Progression in the African Descent and Glaucoma Evaluation Study (ADAGES): Eleven Years of Follow-up.

PURPOSE: To compare the rates of visual field (VF) progression between individuals of Black and White race and to investigate whether treatment effects may help explain differences previously reported between racial groups. DESIGN: Multicenter prospective observational cohort study. METHODS: Participants were patients in referral tertiary care glaucoma clinics with open angle glaucoma. Eyes were excluded who had <5 VF tests and <2 years of follow-up or any disease that could affect the optic nerve or the VF. The VF mean deviation (MD) slopes over time (dB/y) were calculated with linear regression models. Socioeconomic variables, rates of glaucoma surgery, medications, treated intraocular pressure (IOP), and central corneal thickness (CCT) were investigated. RESULTS: A total of 516 eyes were included with a mean (95% CI) follow-up time of 11.0 (range, 10.5-11.5) years and 15.0 (range, 14.1-15.8) visits. Participants of Black race were significantly younger (59.7 vs 66.9 years, P < .01) than those of White race. The mean CCT and socioeconomic variables were similar between Black and White groups (P = 0.20 and P = .56, respectively), as were treatment with topical medications (P = .90) and the rate of VF MD change (-0.24 [-0.31 to -0.17] dB/year vs -0.32 [-0.36 to -0.27], P = .11), despite higher treated mean IOP (14.9 [14.5 to 15.4] vs 14.0 [13.6 to 14.4] mm Hg, P = .03) and fewer trabeculectomies (29.5% vs 50.0%, P < .01) in the Black race group. CONCLUSIONS: Rates of VF progression were similar despite higher treated IOP in the Black race group. Mitigation of health access disparities in this study may have equalized previously reported different rates of VF progression between racial groups.

Relationship between mean follow-up intraocular pressure, rates of visual field progression and current target intraocular pressure guidelines.

AIMS: To investigate if eyes presenting intraocular pressure (IOP) within the limits of current guideline-driven target IOP indeed experience slow rates of glaucomatous visual field (VF) progression. METHODS: A total of 8598 24-2 VF tests from 603 eyes from the African Descent and Glaucoma Evaluation Study with manifest glaucoma were included. The sample was split into three groups based on baseline VF mean deviation (MD): G1 (better than -5.0 dB), G2 (-5.0 to -10 dB) and G3 (worse than -10 dB). We investigated the relationship between existing target IOP guidelines and rates of MD progression in these groups. RESULTS: For stable eyes, the medians and IQR of the mean follow-up IOP were G1=15.0 mmHg (IQR: 13.1 to 17.7), G2=13.2 mmHg (IQR: 11.6 to 14.3) and G3=11.9 mmHg (IQR: 10.1 to 13.8) (p<0.01). When considering the mean follow-up IOP within the limits proposed by current guidelines, the median MD slopes were: -0.20 dB/y (IQR: -0.43 to -0.02) for G1<21 mmHg, -0.19 dB/y (IQR: -0.51 to -0.01) for G2<18 mmHg and -0.15 dB/y (IQR: -0.47 to 0.05) for G3<15 mmHg (p=0.63). There were no significant differences between racial groups. CONCLUSION: In a sample of patients with manifest glaucoma, despite substantial variability between eyes, adherence to treatment guidelines helped slow the rates of global VF progression at various stages of disease. TRIAL REGISTRATION NUMBER: clinicaltrials.gov Identifier: NCT00221923.

Variability and Power to Detect Progression of Different Visual Field Patterns.

PURPOSE: To compare the variability and ability to detect visual field (VF) progression of 24-2, central 12 locations of the 24-2 and 10-2 VF tests in eyes with abnormal VFs. DESIGN: Retrospective, multisite cohort. PARTICIPANTS: A total of 52 806 24-2 and 11 966 10-2 VF tests from 7307 eyes from the Glaucoma Research Network database were analyzed. Only eyes with ≥ 5 visits and ≥ 2 years of follow-up were included. METHODS: Linear regression models were used to calculate the rates of mean deviation (MD) change (slopes), whereas their residuals were used to assess variability across the entire MD range. Computer simulations (n = 10 000) based on real MD residuals of our sample were performed to estimate power to detect significant progression (P < 5%) at various rates of MD change. MAIN OUTCOME MEASURES: Time required to detect progression. RESULTS: For all 3 patterns, the MD variability was highest within the -5 to -20 decibel (dB) range and consistently lower with the 10-2 compared with 24-2 or central 24-2. Overall, time to detect confirmed significant progression at 80% power was the lowest with 10-2 VF, with a decrease of 14.6% to 18.5% when compared with 24-2 and a decrease of 22.9% to 26.5% when compared with central 24-2. CONCLUSIONS: Time to detect central VF progression was reduced with 10-2 MD compared with 24-2 and C24-2 MD in glaucoma eyes in this large dataset, in part because 10-2 tests had lower variability. These findings contribute to current evidence of the potential value of 10-2 testing in the clinical management of patients with glaucoma and in clinical trial design.

Did the OCT Show Progression Since the Last Visit?

Identifying progression is of fundamental importance to the management of glaucoma. It is also a challenge. The most sophisticated, and probably the most useful, commercially available clinical tool for identifying progression is the Guided Progression Analysis (GPA), which was initially developed to identify progression using 24-2 visual field tests. More recently, it has been extended to retinal nerve fiber layer (RNFL) and ganglion cell+inner plexiform layer thicknesses measured with optical coherence tomography (OCT). However, the OCT GPA requires a minimum of 3 tests to determine "possible loss (progression)" and a minimum of 4 tests to determine if the patient shows "likely loss (progression)." Thus, it is not designed to answer a fundamental question asked by both the clinician and the patient, namely: Did damage progress since the last visit? Some clinicians use changes in summary statistics, such as global/average circumpapillary RNFL thickness. However, these statistics have poor sensitivity and specificity due to segmentation and alignment errors. Instead of relying on the GPA analysis or summary statistics, one needs to evaluate RNFL and ganglion cell+inner plexiform layer probability maps and circumpapillary OCT B-scan images. In addition, we argue that the clinician can make a better decision about suspected progression between 2 test days by topographically comparing the changes in the different OCT maps and images, in addition to topographically comparing the changes in the visual field with the changes in OCT probability maps.