The association between glaucoma treatment adherence with disease progression and loss to follow-up.

Prospective cohort study from Brazil to evaluate glaucoma treatment adherence using a medication event monitoring system (MEMS) device and correlate with glaucoma progression and loss to follow-up (LTF) after one year of follow up. We included primary open glaucoma (POAG) patients treated with at least one ocular hypotensive eye drop. MEMS devices was used to monitor adherence for 60 days and evaluate the percentage of doses prescribed taken within the 60-day period. We classified patients according to rates of adherence: low adherence (less than 75% from MEMS measurements) and high adherence (more than 75% from MEMS measurements). We applied a questionnaire to investigated self-reported behavior towards treatment behaviors (glaucoma treatment compliance assessment tool, GTCAT). We also correlated rates of treatment adherence with clinical, demographical variables and the occurrence of glaucoma progression or LTF after one year of observation. We included 110 POAG patients and found that 28.18% of them were considered low adherent. We identify several variables associated with poor adherence such as glaucoma progression, LTF, younger age, low educational and income levels, absence of health insurance, years of disease and peak intraocular pressure. Several constructs from the self-reported GTCAT were also correlated with the rates of treatment adherence. To date, this is the first study in Latin America to evaluate glaucoma treatment adherence with MEMS devices and correlate adherence rates with glaucoma progression and LTF. We found a low-adherence rate of 28.18% and several additional risk factors were statistically associated with poor adherence.

OCT Segmentation Errors with Bruch's Membrane Opening-Minimum Rim Width as Compared with Retinal Nerve Fiber Layer Thickness.

OBJECTIVE: To compare the magnitude and location of automated segmentation errors of the Bruch's membrane opening-minimum rim width (BMO-MRW) and retinal nerve fiber layer thickness (RNFLT). DESIGN: Cross-sectional study. PARTICIPANTS: We included 162 glaucoma suspect or open-angle glaucoma eyes from 162 participants. METHODS: We used spectral-domain optic coherence tomography (Spectralis 870 nm, Heidelberg Engineering) to image the optic nerve with 24 radial optic nerve head B-scans and a 12-degree peripapillary circle scan, and exported the native "automated segmentation only" results for BMO-MRW and RNFLT. We also exported the results after "manual refinement" of the measurements. MAIN OUTCOME MEASURES: We calculated the absolute and proportional error globally and within the 12 30-degree sectors of the optic disc. We determined whether the glaucoma classifications were different between BMO-MRW and RNFLT as a result of manual and automatic segmentation. RESULTS: The absolute error mean was larger for BMO-MRW than for RNFLT (10.8 µm vs. 3.58 µm, P < 0.001). However, the proportional errors were similar (4.3% vs. 4.4%, P = 0.47). In a multivariable regression model, errors in BMO-MRW were not significantly associated with age, location, magnitude, or severity of glaucoma loss (all P ≥ 0.05). However, larger RNFLT errors were associated with the superior and inferior sector location, thicker nerve fiber layer, and worse visual field (all P < 0.05). Errors in BMO-MRW and RNFLT were not likely to occur in the same sector location (R2 = 0.001; P = 0.15). With manual refinement, the glaucoma classification changed in 7.8% and 6.2% of eyes with BMO-MRW and RNFLT, respectively. CONCLUSIONS: Both BMO-MRW and RNFLT measurements included segmentation errors, which did not seem to have a common location, and may result in differences in glaucoma classification. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Detectability of Visual Field Defects in Glaucoma Using Moving Versus Static Stimuli for Perimetry.

Purpose: We have previously shown that using moving, instead of static, stimuli extends the effective dynamic range of automated perimetry in glaucoma. In this study, we further investigate the effect of using moving stimuli on the detectability of functional loss. Methods: We used two experimental perimetry paradigms to test 155 subjects with a diagnosis of glaucoma or glaucoma suspect, and 34 healthy control subjects. One test used stimuli moving parallel to the average nerve fiber bundle orientation at each location; the other used static stimuli. Algorithms were otherwise identical. Sensitivities to moving stimuli were transformed to the equivalent values for static stimuli based on a Bland-Altman plot. The proportions of locations outside age-corrected normative limits were compared, and test-retest variability was compared against defect depth for each stimulus type. Results: More tested locations were below the fifth percentile of the normative range for that location using static stimuli. However, among locations abnormal according to standard clinical perimetry on the same day, 19.2% were abnormal using static stimuli, versus 20.5% using moving stimuli (P = 0.372). Test-retest variability was 44% lower for moving stimuli across the range of defect depths. Conclusions: When compared with static automated perimetry and expressed on a common scale, moving stimuli extend the effective dynamic range and decrease variability, without decreasing the detectability of known functional defects. Translational Relevance: Moving stimuli provide a method to improve known problems of current clinical perimetry.

Patients with Low Vision Struggle with Placing Eye Drops and Benefit from an Eye Drop Aid.

PURPOSE: To evaluate eye drop self-administration in a low-vision patient population and test whether a nose-pivoted drop delivery device (NPDD, GentleDrop) can improve eye drop delivery in these patients. DESIGN: Repeated-measures case series. PARTICIPANTS: Thirty subjects (58 eyes) with low vision, defined as best-corrected visual acuity worse than 20/60 or visual field worse than 20° in the better-seeing eye. METHODS: We video-recorded subjects while self-administering eye drops using their own traditional delivery at baseline, after a standardized teaching, and with an NPDD. Two masked graders independently reviewed each drop delivery. Primary success was defined as the drop reaching the eye without the bottle touching the eye or eyelids. Subjects rated ease-of-use (1-10 scale, 10 = easiest) after each drop delivery and completed a satisfaction survey, which included asking whether subjects could place drops independently (1-5 scale, 5 = most independent). MAIN OUTCOME MEASURES: Logistic-transformed generalized estimating equation regression to compare technique satisfaction, ease-of-use, independence, no contact, and success. RESULTS: Primary success was observed in 30 (52%) of 58 eyes at baseline and increased to 44 eyes (76%) with an NPDD (P = 0.013). Bottle tip contact occurred in 23 (40%) of 58 eyes at baseline and 8 eyes (14%) with an NPDD (P = 0.004). Mean ease-of-use scores were 6.7 ± 3.1 at baseline and 8.3 ± 1.8 (P < 0.001) with an NPDD. Likewise, the NPDD improved success, bottle tip contact, and ease-of-use compared with post-teaching traditional delivery (P < 0.01). Twenty-two (73%) of 30 subjects preferred the NPDD to traditional delivery. Twenty-nine (97%) thought the NPDD was comfortable to use, and all would recommend the device. A subgroup analysis was performed on 16 subjects that self-reported difficulty instilling drops at baseline. The NPDD showed similar results, and it increased confidence in placing drops independently (4.6 ± 0.9) compared with baseline (2.7 ± 1.6, P < 0.001). Fifteen (94%) subjects in this subgroup preferred the NPDD. CONCLUSIONS: Low-vision subjects struggled to self-administer eye drops. An NPDD can improve bottle tip contact, ease-of-use, satisfaction, and independence. Eye care providers could consider screening low-vision patients about difficulty with eye drop self-administration and recommending eye drop aids. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Eye Drop Adherence With an Eye Drop Bottle Cap Monitor.

PRCIS: An eye drop bottle cap monitor with audio and visual alarms measured eye drop adherence in 50 subjects with glaucoma. Baseline adherence rates were too high to test if the alarms could improve adherence. PURPOSE: To determine if an eye drop bottle cap monitor can measure and improve adherence. MATERIALS AND METHODS: The Devers Drop Device (D3, Universal Adherence LLC) was designed to measure eye drop adherence by detecting bottle cap removal and replacement, and it can provide text, visual and audio alerts when a medication is due. In Stage 1, we determined baseline adherence for 50 subjects using a nightly eye drop over a 25-day period. Subjects with less than 90% baseline adherence were eligible for Stage 2. In Stage 2, we randomized subjects to receive either no reminder or automated D3 alerts for their nightly eye drop over a subsequent 25-day period. We defined adherence as the proportion of drops administered within 3 hours of the subjects' scheduled dosing time. Subjects completed 3 questions regarding satisfaction with the device and willingness to pay. RESULTS: The D3 monitor remained attached to the eye drop bottle cap for the duration of the study and collected adherence data in all 50 patients. In Stage 1, the mean adherence rate was 90 ± 18% (range 32-100%). Forty (80%) subjects had an adherence rate greater than 90%. Adherence rates were too high in Stage 1 to adequately test the effects of reminders in Stage 2. Ninety-eight percent (49/50) and 96% (48/50) of subjects agreed "the device always stayed attached to the bottle cap" and "I was able to use the device to take the drops", respectively. Patients would pay $61±83 (range $0-400) for a similar device to improve adherence. CONCLUSIONS: The D3 can measure eye drop adherence. Research subjects reported high satisfaction and willingness to pay for an eye drop bottle cap monitor. Glaucoma patients have high adherence when they are being monitored, and future studies with research subjects screened for poor adherence may further determine the benefit of electronic monitoring of adherence with and without electronic reminders.

Optic nerve cavitations in glaucoma suspect and glaucoma patients.

Purpose: Glaucoma is associated with structural changes of the optic nerve head such as deformation, lamina cribosa defects, prelaminar schisis, and peripapillary retinal schisis. We describe optic nerve cavitations that were detected by routine spectral domain optical coherence tomography (OCT). Observations: OCT imaging showed cavitations in 5 eyes of 4 patients with an initial diagnosis of glaucoma or glaucoma suspect. The cavitations were seen as hyporeflective spaces that are sharply delineated from surrounding tissue. They were centered inferonasally, anterior to the lamina cribosa, and at least partially within the Bruch's membrane opening (BMO). They extended from 3 to 6 clock hours. Conclusion: AND IMPORTANCE: We describe a new OCT finding in patients with a diagnosis of glaucoma and glaucoma suspect. While previous reports describe cavitations in the choroid in patients with pathological myopia, our patients had minimal refractive error and the cavitations were located within the optic nerve. We will examine these patients over time to determine the impact of this finding on longitudinal changes in structure and function.

Moving Stimulus Perimetry: A New Functional Test for Glaucoma.

Purpose: Static pointwise perimetric sensitivities of less than approximately 19 dB are unreliable in glaucoma owing to excessive variability. We propose using moving stimuli to increase detectability, decrease variability, and hence increase this dynamic range. Methods: A moving stimulus was designed to travel parallel to the average nerve fiber bundle orientation at each location, and compared against an otherwise identical static stimulus. To assess dynamic range, psychometric functions were measured at 4 locations of each of 10 subjects. To assess clinically realistic test-retest variability, 34 locations of 94 subjects with glaucoma and glaucoma suspects were tested twice, 6 months apart. Pointwise sensitivity estimates were compared using generalized estimating equation regression models. The test-retest limits of agreement for each stimulus were assessed, adjusted for within-eye clustering. Results: Using static stimuli, 9 of the 40 psychometric functions had less than a 90% maximum response probability, suggesting being beyond the dynamic range. Eight of those locations had asymptotic maximum of more than 90% with moving stimuli. Sensitivities were higher for moving stimuli (P < 0.001); the difference increased as sensitivity decreased (P < 0.001). Test-retest limits of agreement were narrower for moving stimuli (-6.35 to +6.48 dB) than static stimuli (-12.7 to +7.81 dB). Sixty-two percent of subjects preferred using moving stimuli versus 19% who preferred static stimuli. Conclusions: Using a moving stimulus increases perimetric sensitivities in regions of glaucomatous loss. This extends the effective dynamic range, allowing reliable testing later into the disease. Results are more repeatable, and the test is preferred by most subjects. Translational Relevance: Moving stimuli allow reliable testing in patients with more severe glaucoma than currently possible.

Geospatial analysis of blindness within rural and urban counties.

PURPOSE: To determine the associations of blindness within rural and urban counties using a registry of blind persons and geospatial analytics. METHODS: We used the Oregon Commission for the Blind registry to determine the number of persons who are legally blind, as well as licensure data to determine the density of eye care providers (optometrists and ophthalmologists) within each county of the State of Oregon. We used geospatial statistics, analysis of variance, and logistic regression to determine the explanatory variables associated with blindness within counties. RESULTS: We included 8350 individuals who are legally blind within the state of Oregon in the calendar year 2015. The mean observed prevalence of registered blindness was 0.21% and ranged almost 9-fold from 0.04% to 0.58% among counties (p < .001). In univariate models, higher blindness was associated with increasing median age (p = .027), minority race (p < .001), decreased median household income (p < .001), increased poverty within a county (p < .001), and higher density of ophthalmologists (p = .003). Density of optometrists was not associated with prevalence of blindness (p = .89). The final multivariable model showed higher blindness to be associated with lower median household income, higher proportion of black race, and lower proportion of Hispanic race (p < .001 for all). CONCLUSION: Geospatial analytics identified counties with higher and lower than expected proportions of blindness even when adjusted for sociodemographic factors. Clinicians and researchers may use the methods and results of this study to better understand the distribution of individuals with blindness and the associated factors to help design public health interventions.

Long- and Short-Term Variability of Perimetry in Glaucoma.

Purpose: Test-retest variability in perimetry consists of short-term and long-term components, both of which impede assessment of progression. By minimizing and quantifying the algorithm-dependent short-term variability, we can quantify the algorithm-independent long-term variability that reflects true fluctuations in sensitivity between visits. We do this at locations with sensitivity both < 28 dB (when the stimulus is smaller than Ricco's area and complete spatial summation can be assumed) and > 28 dB (when partial summation occurs). Methods: Frequency-of-seeing curves were measured at four locations of 35 participants with glaucoma. The standard deviation of cumulative Gaussian fits to those curves was modeled for a given sensitivity and used to simulate the expected short-term variability of a 30-presentation algorithm. A separate group of 137 participants was tested twice with that algorithm, 6 months apart. Long-term variance at different sensitivities was calculated as the LOESS fit of observed test-retest variance minus the LOESS fit of simulated short-term variance. Results: Below 28 dB, short-term variability increased approximately linearly with increasing loss. Long-term variability also increased with damage below this point, attaining a maximum standard deviation of 2.4 dB at sensitivity 21 dB, before decreasing due to the floor effect of the algorithm. Above 30 dB, the observed test-retest variance was slightly smaller than the simulated short-term variance. Conclusions: Long-term and short-term variability both increase with damage for perimetric stimuli smaller than Ricco's area. Above 28 dB, long-term variability constitutes a negligible proportion of test-retest variability. Translational Relevance: Fluctuations in true sensitivity increase in glaucoma, even after accounting for increased short-term variability. This long-term variability cannot be reduced by altering testing algorithms alone.

Intraocular Pressure and Medication Burden With Cataract Surgery Alone, or Cataract Surgery Combined With Trabecular Bypass or Goniotomy.

PRCIS: When compared with cataract surgery in glaucoma patients, trabecular micro-bypass and goniotomy resulted in a large decrease in the incidence of intraocular pressure (IOP) spikes, a modest effect on IOP, and a minimal effect on medication burden. PURPOSE: To compare changes in IOP and ocular hypotensive medications in 3 surgical cohorts: cataract surgery, cataract surgery with trabecular micro-bypass (cataract/trabecular), and cataract surgery with goniotomy (cataract/goniotomy). MATERIALS AND METHODS: We included 138 eyes diagnosed with open-angle glaucoma: (1) 84 eyes with cataract surgery alone, (2) 25 eyes with cataract/trabecular surgery, and (3) 29 eyes with cataract/goniotomy surgery. We compared the groups for postoperative IOP and the number of ocular hypotensive medications. We adjusted for preoperative IOP, and preoperative and postoperative number of ocular hypotensive medications. We defined an IOP spike as IOP ≥21 mm Hg and 10 mm Hg higher than preoperative on postoperative day 1. RESULTS: All 3 surgeries showed a decrease in IOP (P≤0.004) and medication burden (P≤0.001) at 3 and 6 months postoperatively when compared with their own preoperative baselines. When compared with cataract surgery alone, cataract/trabecular and cataract/goniotomy had similar IOP lowering at 1 month postoperatively, and variable results at 3 and 6 months. The change in ocular hypotensive medications was not statistically different between the surgical groups at any postoperative visit. Cataract/trabecular and cataract/goniotomy decreased IOP on postoperative day 1, and had relative risk reduction of ~70% for IOP spikes (P≤0.001 for both). CONCLUSION: Trabecular micro-bypass and goniotomy when added to cataract surgery resulted in a large decrease in IOP spikes, a modest effect on IOP, and a minimal effect on medication burden when compared with cataract surgery alone in glaucoma patients.

Clinicians' Use of Quantitative Information while Assessing the Rate of Functional Progression in Glaucoma.

PURPOSE: Clinicians use both global and point-wise information from visual fields to assess the rate of glaucomatous functional progression. We asked which objective, quantitative measures best correlated with subjective assessment by glaucoma experts. In particular, we aimed to determine how much that judgment was based on localized rates of change vs. on global indices reported by the perimeter. DESIGN: Prospective cohort study. PARTICIPANTS: Eleven academic, expert glaucoma specialists independently scored the rate of functional progression, from 1 (improvement) to 7 (very rapid progression), for a series of 5 biannual clinical printouts from 100 glaucoma or glaucoma suspect eyes of 51 participants, 20 of which were scored twice to assess repeatability. METHODS: Regression models were used to predict the average of the 11 clinicians' scores based on objective rates of change of mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD), the Nth fastest progressing location, and the Nth fastest progressing of 10 anatomically defined clusters of locations after weighting by eccentricity. MAIN OUTCOME MEASURES: Correlation between the objective rates of change and the average of the 11 clinicians' scores. RESULTS: The average MD of the study eyes was -2.4 dB (range, -16.8 to +2.8 dB). The mean clinician score was highly repeatable, with an intraclass correlation coefficient of 0.95. It correlated better with the rate of change of VFI (pseudo-R2 = 0.73, 95% confidence interval [CI, 0.60-0.83]) than with MD (pseudo-R2 = 0.63, 95% CI [0.45-0.76]) or PSD (pseudo-R2 = 0.41, 95% CI [0.26-0.55]). Using point-wise information, the highest correlations were found with the fifth-fastest progressing location (pseudo-R2 = 0.71, 95% CI [0.56-0.80]) and the fastest-progressing cluster after eccentricity weighting (pseudo-R2 = 0.61, 95% CI [0.48-0.72]). Among 25 eyes with an average VFI of > 99%, the highest observed pseudo-R2 value was 0.34 (95% CI [0.16-0.61]) for PSD. CONCLUSIONS: Expert academic glaucoma specialists' assessment of the rate of change correlated best with VFI rates, except in eyes with a VFI near the ceiling of 100%. Sensitivities averaged within clusters of locations have been shown to detect change sooner, but the experts' opinions correlated more closely with global VFI. This could be because it is currently the only index for which the perimeter automatically provides a quantitative estimate of the rate of functional progression.

Clinicians' Use of Quantitative Information When Assessing the Rate of Structural Progression in Glaucoma.

PURPOSE: OCT scans contain large amounts of information, but clinicians often rely on reported layer thicknesses when assessing the rate of glaucomatous progression. We sought to determine which of these quantifications most closely relate to the subjective assessment of glaucoma experts who had all the diagnostic information available. DESIGN: Prospective cohort study. PARTICIPANTS: Eleven glaucoma specialists independently scored the rate of structural progression from a series of 5 biannual clinical OCT printouts. METHODS: A total of 100 glaucoma or glaucoma suspect eyes of 51 participants were included; 20 were scored twice to assess repeatability. Scores ranged from 1 (improvement) to 7 (very rapid progression). Generalized estimating equation linear models were used to predict the mean clinician score from the rates of change of retinal nerve fiber layer thickness (RNFLT) or minimum rim width (MRW) globally or in the most rapidly thinning of the 6 sectors. MAIN OUTCOME MEASURES: The correlation between the objective rates of change and the average of the 11 clinicians' scores. RESULTS: Average RNFLT within the series of study eyes was 79.3 µm (range, 41.4-126.6). Some 95% of individual clinician scores varied by ≤ 1 point when repeated. The mean clinician score was more strongly correlated with the rate of change of RNFLT in the most rapidly changing sector in %/year (pseudo-R2 = 0.657) than the rate of global RNFLT (0.372). The rate of MRW in the most rapidly changing sector had pseudo-R2 = 0.149. CONCLUSIONS: The rate of change of RNFLT in the most rapidly changing sector predicted experts' assessment of the rate of structural progression better than global rates or MRW. Sectoral rates may be a useful addition to current clinical printouts.

Cataract Surgery Lowers Intraocular Pressure and Medication Use in the Medication Group of the Ocular Hypertension Treatment Study.

PURPOSE: To determine the change in intraocular pressure (IOP) and ocular hypotensive medication use after cataract extraction in the Medication Group of the Ocular Hypertension Treatment Study. DESIGN: Secondary analysis of randomized clinical trial data. METHODS: We included 92 participants (n = 149 eyes) of the Medication Group of the Ocular Hypertension Treatment Study who underwent cataract surgery in at least 1 eye during the study and 531 participants (n = 1004 eyes) of the Medication Group who did not undergo cataract surgery. We defined the "split date" as the first study visit that cataract surgery was reported for the cataract surgery group and the 15th visit in the control group to equalize the median number of visits. We then compared the 2 groups at visits relative to this split date. MAIN OUTCOME MEASURES: Difference in preoperative and postoperative IOP, and number of classes of ocular hypotensive medications between the cataract and control group over a 72-month period. RESULTS: Cataract surgery significantly decreased the number of ocular hypotensive medications at all postoperative visits (mean, -0.4 medications; P ≤ .005) through the 48-month postoperative visit when compared with the control group. At the split date, approximately 23% of eyes were medication free and 41% had a reduced medication burden. Cataract surgery resulted in a decrease in IOP (P < .001), but the difference in IOP between the groups reduced over time and became nonsignificant after 12 months. CONCLUSIONS: Cataract surgery in patients with ocular hypertension produced sustained reductions in the average number of ocular hypotensive medications and transient reductions in IOP.

Novel Eye Drop Delivery Aid Improves Outcomes and Satisfaction.

PURPOSE: To compare a nose-pivoted drop delivery device (NPDD) with traditional eye drop delivery in glaucoma subjects. DESIGN: Repeated-measures case series. PARTICIPANTS: Fifty glaucoma subjects (100 eyes) who reported difficulty self-administering eye drops. METHODS: We compared eye drop delivery using a NPDD against traditional delivery techniques at baseline (baseline traditional) and after standardized teaching (post-teaching traditional). Subjects used a 1-to-10 scale (10 being easiest) to rate the ease of delivery with each technique and completed a satisfaction survey. Two graders used digital video to independently review eye drop delivery and recorded: (1) accurate placement: the eye drop reached the ocular surface; (2) no contact: no bottle tip contact against the ocular or periocular surface; and (3)number of eye drops dispensed. We defined primary success as accurate placement and no contact; secondary success as primary success with only 1 drop dispensed. MAIN OUTCOME MEASURES: We used logistic-transformed generalized estimating equation (GEE) regression to compare technique satisfaction, accuracy, no contact, and primary and secondary success. Number of drops dispensed was compared using a Cox model. RESULTS: Forty-seven of 50 subjects (94%) preferred the NPDD over traditional eye drop delivery. The mean score for ease of use was higher for the NPDD (8.9 ± 1.1) than baseline traditional (6.7 ± 2.1; P < 0.001) and post-teaching traditional (7.0 ± 2.0; P < 0.001). Forty-nine of 50 (98%) subjects thought the NPDD was comfortable to use and would recommend the device. The eye drop reached the ocular surface in a similar percentage of subjects (>90%) with each method. The bottle tip contacted fewer eyes with the NPDD (10 eyes) than baseline traditional (33 eyes; P < 0.001) and post-teaching traditional (25 eyes; P = 0.009). The number of drops dispensed was lower with the NPDD (1.7 ± 1.2) than baseline traditional (2.2 ± 1.6; P = 0.017) and post-teaching traditional (2.4 ± 1.8; P = 0.006). The NPDD increased primary and secondary success of eye drop delivery (86% and 54%, respectively) compared to baseline traditional (66% [P = 0.001] and 28% [P < 0.001]) and post-teaching traditional (70% [P = 0.005] and 40% [P = 0.018]). CONCLUSIONS: Eye drop users preferred the NPDD over traditional eye drop delivery. The NPDD improved eye drop delivery success, reduced bottle tip contact, and decreased the number of eye drops wasted.

Association of Optic Nerve Head Prelaminar Schisis With Glaucoma.

PURPOSE: To compare the frequency of observing optic nerve head (ONH) prelaminar schisis by optical coherence tomography (OCT) in glaucoma and glaucoma suspect (GL/S) eyes vs healthy control (HC) eyes and to assess its association with other markers of glaucoma severity. METHODS: This cross-sectional study included 298 eyes of 150 GL/S patients and 88 eyes of 44 HCs. OCT scans were obtained, including 24 radial B-scans, each composed of 768 A-lines spanning 15°, centered on the ONH. Two reviewers masked to all other clinical, demographic, and ocular information independently graded the OCT scans for the presence of ONH prelaminar schisis on a 4-point scale of 0 (none) to 3 (severe). The probability of ONH schisis was compared between groups and against demographic and ocular factors, including structural and functional measures of glaucoma severity. RESULTS: The frequency and severity of ONH prelaminar schisis were greater in GL/S than in HC (P = .009). Among the GL/S group, 165 eyes (55.4%) had no visible schisis (Grade 0), 71 (23.8%) had Grade 1, 46 (15.4%) had Grade 2 and 16 (5.4%) had Grade 3 schisis. Among HC eyes, 59 (67.0%) had Grade 0, 24 (27.3%) had Grade 1, 5 (5.7%) had Grade 2, none had Grade 3. ONH schisis was more common in eyes with thinner MRW and a deeper cup. CONCLUSIONS: ONH prelaminar schisis may be a sign of glaucomatous deformation and reflect ongoing pathophysiological damage. ONH prelaminar schisis can impact OCT image segmentation and diagnostic parameters, resulting in substantial overestimation of the true rim tissue thickness and underestimation of cup depth.

Time Lag Between Functional Change and Loss of Retinal Nerve Fiber Layer in Glaucoma.

Purpose: It is often suggested that structural change is detectable before functional change in glaucoma. However, this may be related to the lower variability and hence narrower normative limits of structural tests. In this study, we ask whether a time lag exists between the true rates of change in structure and function, regardless of clinical detectability of those changes. Methods: Structural equation models were used to determine whether the rate of change in function (mean linearized total deviation, AveTDLin) or structure (retinal nerve fiber layer thickness [RNFLT]) was predicted by the concurrent or previous rate for the other modality, after adjusting for its own rate in the previous time interval. Rates were calculated over 1135 pairs of consecutive visits from 318 eyes of 164 participants in the Portland Progression Project, with mean 207 days between visits. Results: The rate of change of AveTDLin was predicted by its own rate in the previous time interval, but not by rates of RNFLT change in either the concurrent or previous time interval (both P > 0.05). Similarly, the rate of RNFLT change was not predicted by concurrent AveTDLin change after adjusting for its own previous rate. However, the rate of AveTDLin change in the previous time interval did significantly improve prediction of the current rate for RNFLT, with P = 0.005, suggesting a time lag of around six months between changes in AveTDLin and RNFLT. Conclusions: Although RNFL thinning may be detectable sooner, true functional change appears to predict and precede thinning of the RNFL in glaucoma.

Detection of functional deterioration in glaucoma by trend analysis using comprehensive overlapping clusters of locations.

Detecting rapid visual field deterioration is crucial for individuals with glaucoma. Cluster trend analysis detects visual field deterioration with higher sensitivity than global analyses by using predefined non-overlapping subsets of visual field locations. However, it may miss small defects that straddle cluster borders. This study introduces a comprehensive set of overlapping clusters, and assesses whether this further improves progression detection. Clusters were defined as locations from where ganglion cell axons enter the optic nerve head within a θ° wide sector, centered at 1º intervals, for various θ. Deterioration in eyes with or at risk of glaucomatous visual field loss was "detected" if ≥ Nθ clusters had deteriorated with p < pCluster, chosen empirically to give 95% specificity based on permuting the series. Nθ was chosen to minimize the time to detect subsequently-confirmed deterioration in ≥ 1/3rd of eyes. Times to detect deterioration were compared using Cox survival models. Biannual series were available for 422 eyes of 214 participants. Predefined non-overlapping clusters detected subsequently-confirmed change in ≥ 1/3rd of eyes in 3.41 years (95% confidence interval 2.75-5.48 years). After equalizing specificity, no criteria based on comprehensive overlapping clusters detected deterioration significantly sooner. The quickest was 3.13 years (2.69-4.65) for θ° = 20° and Nθ = 25, but the comparison with non-overlapping clusters had p = 0.672. Any improvement in sensitivity for detecting deterioration when using a comprehensive set of overlapping clusters was negated by the need to maintain equal specificity. The existing cluster trend analysis using predefined non-overlapping clusters provides a useful tool for monitoring visual field progression.