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. Author manuscript; available in PMC: 2007 Aug 9.
Published in final edited form as: Arch Ophthalmol. 2005 Apr;123(4):464–470. doi: 10.1001/archopht.123.4.464

Optical Coherence Tomography Longitudinal Evaluation of Retinal Nerve Fiber Layer Thickness in Glaucoma

Gadi Wollstein 1,2, Joel S Schuman 1,2, Lori L Price 3, Ali Aydin 1, Paul C Stark 3, Ellen Hertzmark 4, Edward Lai 1, Hiroshi Ishikawa 1,2, Cynthia Mattox 1, James G Fujimoto 5, Lelia A Paunescu 1
PMCID: PMC1941777  NIHMSID: NIHMS24584  PMID: 15824218

Abstract

Objectives

To longitudinally evaluate optical coherence tomography (OCT) peripapillary retinal nerve fiber layer (RNFL) thickness measurements and to compare RNFL thickness over time to clinical status and automated perimetry.

Methods

Retrospective evaluation of 64 eyes (37 subjects) of glaucoma suspects and glaucoma patients participating in a prospective longitudinal study. All participants had comprehensive clinical assessment, visual field (VF) testing and OCT scanning every 6 months. Field progression was defined as reproducible drop of at least 2dB of VF mean deviation (VF-MD) from baseline visit. OCT progression was defined as reproducible mean RNFL thinning of at least 20μm.

Results

With a median follow-up of 4.7 years, subjects had a median of 5 usable OCT scans. The difference in the linear regression slopes of RNFL thickness between glaucoma suspects and glaucoma patients was found to be non-significant for all parameters; however, Kaplan-Meier survival curve analysis demonstrated a higher progression rate by OCT than by VF. 66% of eyes were stable throughout the duration of follow-up, 22% progressed by OCT alone, 9% by VF-MD alone and 3% by both VF and OCT.

Conclusions

A greater likelihood of glaucomatous progression was identified by OCT compared to automated perimetry. This might reflect either OCT hypersensitivity or true damage identified by OCT prior to detection by conventional means.

Glaucoma is characterized by a combination of structural and functional damage. Previous studies have indicated that structural changes in glaucoma patients as detected by optic disc and/or nerve fiber layer assessment precede functional changes detected by perimetry.1–10

In recent years glaucoma imaging modalities were incorporated into the management of glaucoma patients. These imaging modalities were designed to detect morphological glaucomatous abnormalities and might improve the ability to detect longitudinal changes utilizing quantitative measurements. Several cross-sectional studies have demonstrated the capability of these modalities to identify glaucomatous changes.11–25 Limited information, however, is available as to their use for longitudinal glaucoma assessment.9

Optical coherence tomography (OCT) is a high resolution glaucoma imaging device capable of obtaining reproducible retinal and nerve fiber layer thickness measurements.26–28 This device has been shown in cross-sectional studies to allow differentiation between normals and glaucoma patients.11, 18, 29–35

The purpose of this study is to longitudinally evaluate optical coherence tomography (OCT) circumpapillary retinal nerve fiber layer (RNFL) measurements as compared to standard clinical assessment and automated perimetry.

Methods

Data for this study were retrospectively collected from a prospective longitudinal study carried out in the glaucoma service at New England Eye Center, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, between 1994 and 2001. All subjects attending the service willing to participate in the study and qualified according to the criteria below were included. Institutional Review Board (IRB) / Ethics Committee approval was obtained for the study and all participants gave their approval to participate in the study. This study followed the principles of the Declaration of Helsinki.

Patients were included in the study according to the following inclusion criteria: best corrected visual acuity of 20/60 or better, refractive error between +3.00 to −6.00 diopters and at least five reliable VF tests and five good quality OCT scans. The exclusion criteria were: subjects with a history of diabetes as well as eyes with signs of posterior pole pathology other than those attributed to glaucoma or significant media opacity in which the fundus was not visible. Eyes that underwent cataract extraction or any other intraocular surgery within the period of follow-up were excluded from the study.

Study protocol

All subjects underwent thorough baseline ophthalmic evaluation including medical history, intraocular pressure (IOP) measurement, undilated and dilated biomicroscopy, visual field (VF) testing and OCT scanning. Both eyes were included in the study if they were found to be eligible.

All subjects were scheduled for follow-up assessments every 6 months, unless additional visits were medically indicated. Each visit included full ophthalmic evaluation, VF testing and OCT scanning.

Clinical diagnosis

The study population included glaucoma suspects and glaucoma patients. Glaucoma suspect eyes were defined as those with no history of retinal pathology, laser therapy or intra-ocular surgery. An IOP of 22 – 30 mmHg and/or asymmetric ONH cupping (difference in vertical cup / disc ratio greater than 0.2 between the eyes) or abnormal appearing ONH all in the presence of normal VF test were also included in the definition. This group contained suspect eyes from different etiologies such as ocular hypertension, increased cupping (vertical cup / disc ratio > 0.6), asymmetric cupping and family history of glaucoma.

Glaucomatous eyes were defined as those having at least one of the following: 1. A glaucomatous VF defect; 2. IOP > 35 mmHg despite a full VF in the presence of large ONH cupping; 3. nerve fiber layer defect on stereo biomicroscopy.

Visual field testing

All patients underwent Humphrey full-threshold 24-2 achromatic perimetry or Swedish Interactive Thresholding Algorithm (SITA) standard 24-2 perimetry. A reliable VF test was defined as one with fewer than 30% fixation losses, false positive or false negative responses. Normal VF test results were defined as having no cluster of three or more adjacent points depressed more than 5 dB or two adjacent points depressed more than 10 dB in the pattern deviation plot. Abnormal VF test was defined as a cluster of abnormal points as defined above.

Two glaucoma experts independently assessed the VF tests to determine progression between consecutive visits and between first and last visit. The graders were masked to each other, any clinical information, date of test and patient age. The graders were asked to grade the change from previous VF testing as deterioration, no change or improvement and overall assessment of change between the first and last VF tests. Consensus between the graders was required in cases of disagreement.

Eyes were defined for the analysis as VF progressors by subjective assessment when both graders or the consensus agreement, labeled deterioration in the same VF location in 2 of 3 consecutive follow-up VFs. All other eyes were classified as VF non-progressors. Eyes were defined as VF progressors by MD when VF-MD dropped by 2 dB from baseline value in 2 of 3 consecutive follow-up visits. Parameters used for the analysis were VF mean deviation (VF-MD), pattern standard deviation (VF-PSD) and the subjective assessment of the VF. For eyes that were tested by both full-threshold and SITA protocols during the follow-up period, the global VF indices were treated as a continuum.

OCT scanning

OCT is the optical equivalent of B-scan ultrasound where the delay of the backscattered light from the various components of the scanned tissue enables one to differentiate between various tissue layers. Detailed descriptions of OCT have been previously published.26, 36, 37 OCT has been shown to obtain accurate and reproducible RNFL and retinal thickness measurements.26–28

All OCT scans in this study were performed with a prototype device with a reported resolution of 10 μm.26 This device acquired 100 circumpapillary measuring points in approximately 2.5 seconds. RNFL thickness measurements acquired by this device have been shown to be highly correlated with those obtained with a commercially available OCT device (Pakter HM, Schuman JS, Hertzmark E, et al. Measurement of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography. Unpublished data).

All patients had pupillary dilation with 1% tropicamide and 2.5% phenylephrine before recording OCT images. Each patient had 3 circular scans centered on the optic disc with a diameter of 3.4 mm. Poor quality scans were defined as those with signal / noise < 40 or the presence of overt misalignment of the surface detection algorithm of at least 15 consecutive pixels or 20 additive pixels.

Parameters used for the analysis were mean peripapillary RNFL thickness (OCT mean) and two new parameters that were computed for this study: OCT mean deviation (OCT-MD) - the mean difference between each of the 100 measuring points and age adjusted normative values as determined in a previous study (Pakter HM, Schuman JS, Hertzmark E, et al. Measurement of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography. Unpublished data) and OCT pattern standard deviation (OCT-PSD) - the standard deviation of the difference between the measured value and the age adjusted normative value. Confirmed OCT progression was defined as thinning of the mean RNFL of at least 20 μm (based on 2 * reproducibility error of the device26) from the baseline measurement in 2 of 3 consecutive follow-up OCT scans.

Statistical analysis

The data were analyzed using SAS software (SAS Institute, Cary, NC). The mixed procedure in SAS was used to correct for the correlation between measurements from the same patient. Pearson correlations were calculated between VF results and OCT measurements for tests conducted within 6 months from each other. Linear regression was used to determine the slope of change for VF and OCT measurements for each eye over time. The group mean slope was used for the analysis. A significant slope was defined as a slope that significantly differed from a zero slope (p < 0.05).

Kaplan-Meier (K-M) survival curves were used to assess time to progression as defined by the following criteria: OCT mean drop of 20 μm or VF-MD drop of 2 dB from baseline value in 2 of 3 consecutive follow-up visits. The log-rank test was used to compare the K-M curves by diagnosis and subjective assessment of VF. The paired Prentice-Wilcoxon test as suggested by Woolson,38 was used to compare the OCT mean and VF-MD curves to each other.

Results

Fifty-five glaucoma eyes (32 subjects) and 9 glaucoma suspect eyes (5 subjects) qualified for the study. The characteristics of the study population are summarized in Table 1. Within a median follow-up period of 4.7 years the participants had a median of 5 qualified OCT scans. A median of 6 qualified VF tests were performed within a median of 4.2 years of follow-up. 95.3% of OCT and VF tests were conducted within 6 months of each other (Figure 1).

Table 1.

Baseline characteristics of study population

Glaucoma Suspect Glaucoma
Eyes / Subjects 9 / 5 55 / 32
Age (SD) yr 50.9 (15.1) 66.6 (14.4)
Male / Female 2 / 3 12 / 20
Ethnicity (%)
 Eastern Asian
 Afro-American
 Caucasian
0
0
5
2 (6.3)
7 (21.9)
23 (71.9)
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Figure 1.

Figure 1

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Difference in time between VF test and OCT scan (months).

Baseline VF-MD for the glaucoma suspect group was −0.7 ± 2.1 dB and at last visit −1.1 ± 1.7 dB (p = 0.04). Baseline VF-MD for the glaucoma group was −4.1 ± 4.8 dB and at last visit −4.1 ± 5.4 dB (p = 0.67) (Table 2). No significant difference was found between initial and final VF-PSD in neither group. For OCT mean, the initial measure in the glaucoma suspect group was 115.7 ± 36.2 μm and the last visit 111.3 ± 23.0 μm (p = 0.02). In the glaucoma group the initial OCT mean was 94.0 ± 21.9 μm and the final value was 82.3 ± 25.3 μm (p < 0.0001). For both OCT-MD and OCT-PSD the difference between first and last values was significant only in the glaucoma group.

Table 2.

Baseline and last visit results (SD) of visual field and OCT

VF-MD dB VF-PSD dB OCT Mean μm OCT-MD μm OCT-PSD μm
Glaucoma Suspect (N = 9) Baseline −0.67 (2.06) 2.02 (0.82) 115.72 (36.23) −2.90 (35.60) 25.57 (10.16)
Last −1.14 (1.66) 1.80 (0.74) 111.31 (23.01) −5.64 (21.00) 25.46 (10.20)
p 0.04 0.11 0.02 0.31 0.29
Glaucoma (N = 55) Baseline −4.06 (4.77) 4.12 (3.19) 93.97 (21.85) −16.06 (20.83) 28.18 (6.38)
Last −4.08 (5.37) 4.01 (3.57) 82.26 (25.27) −25.77 (24.36) 32.57 (10.43)
p 0.67 0.22 < 0.0001 0.0002 0.002
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VF-MD - visual field mean deviation, VF-PSD - visual field pattern standard deviation, OCT-MD - mean difference between point measurement and age adjusted normative value, OCT-PSD - standard deviation of the mean difference between point measurement and age adjusted normative value

Cross-sectional correlations between OCT measures and global VF indices of tests conducted within 6 months from each other were moderate to good in each visit (Table 3).

Table 3.

Cross-sectional Pearson correlation (r) between OCT measures and VF indices for each visit

OCT-mean p OCT-MD p OCT-PSD p
Visit 1 (N = 64) VF-MD 0.50 <0.0001 0.38 0.002 −0.27 0.03
VF-PSD −0.55 <0.0001 −0.43 0.0004 0.27 0.03
Visit 2 (N = 64) VF-MD 0.43 0.0004 0.43 0.0004 −0.34 0.006
VF-PSD −0.53 <0.0001 −0.45 0.0002 0.38 0.002
Visit 3 (N = 62) VF-MD 0.53 <0.0001 0.54 <0.0001 −0.61 <0.0001
VF-PSD −0.48 <0.0001 −0.40 0.001 0.43 0.0004
Visit 4 (N = 57) VF-MD 0.48 0.0002 0.46 0.0003 −0.43 0.001
VF-PSD −0.53 <0.0001 −0.48 0.0001 0.41 0.002
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VF-MD - visual field mean deviation, VF-PSD - visual field pattern standard deviation, OCT-MD - mean difference between point measurement and age adjusted normative value, OCT-PSD - standard deviation of the mean difference between point measurement and age adjusted normative value

K-M survival curves were used for evaluating time to progression. Overall there was greater likelihood of repeatable OCT mean RNFL drop of 20 μm compared to VF-MD drop of 2 dB from baseline values (p = 0.12) (Figure 2). Altogether, 22/64 eyes were found to progress when applying the repeatable VF-MD drop of 2 dB and repeatable OCT drop of 20 μm criteria. Fourteen (21.9%) eyes progressed by OCT only, 6 (9.4%) by VF only and 2 by both methods (Figure 3). Defining VF-MD progression as a repeatable drop of 1 dB yielded a higher number of VF progressors (12 eyes OCT only, 15 VF only and 4 both methods) while setting the level at 4 dB reduced the number (16 eyes OCT only, 1 VF only and none by both methods) (Figure 4, top and bottom).

Figure 2.

Figure 2

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K-M survival curve for VF-MD and OCT mean RNFL for the entire study group.

Figure 3.

Figure 3

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Proportion of study patients showing no progression, progression with visual field (VF) only (repeatable VF-MD drop of 2 dB from baseline visit), OCT only (repeatable mean RNFL thickness drop of 20 μm from baseline visit), or both VF and OCT.

Figure 4.

Figure 4

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K-M survival curves for OCT mean and VF-MD using cutoff of 1, 2 and 4 dB repeatable drop from baseline value for subjects classified as no subjective VF progression (top) and subjective VF progression (bottom).

The K-M curves using OCT mean did not differ significantly between glaucoma suspects and glaucoma patients (p = 0.72). Similar results were found for K-M curves of OCT mean stratified by subjective VF assessment (p = 0.40).

Comparing OCT mean and VF-MD for subjects defined as progressors or non-progressors by the subjective assessment of VF we found a greater likelihood for progression for OCT mean compared to VF-MD in the VF non-progressor group (p = 0.01) (Figure 5, top). In VF-progressors, the curves overlapped and the difference was not significant (p = 0.31) (Figure 5, bottom).

Figure 5.

Figure 5

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K-M survival curve for OCT mean and VF-MD in the non-progressor (top) and progressor (bottom) groups as defined by subjective assessment of VF.

Linear regression analysis was used as an additional method to assess progression. Mean linear regression slopes for the various VF and OCT parameters for the glaucoma suspects and glaucoma patients are summarized in Table 4. The difference in the slope between the groups was non-significant for all parameters. Stratifying the group based on the subjective assessment of VF into VF-progressors and VF-non progressors, we found a significant difference only for VF-PSD (Table 5). To investigate the possible effect of baseline VF damage on the rate of progression, the group was stratified according to baseline VF-MD above or below −5dB (Table 6). The difference between the groups was non-significant for all the parameters. The power to detect a difference between the groups with an alpha = 0.05 was calculated to be between 5% and 12% for the various parameters.

Table 4.

Mean (SD) linear regression slope for glaucoma suspects and glaucoma patients

Glaucoma suspects (N = 9) Glaucoma (N = 55) p
VF-MD dB/y −0.12 (0.45) 0.04 (0.54) 0.78
VF-PSD dB/y −0.07 (0.16) −0.04 (0.36) 0.77
OCT mean μm/y −2.56 (5.76) −2.21 (4.12) 0.88
OCT-MD μm/y −2.10 (5.75) −1.77 (4.12) 0.87
OCT-PSD μm/y −0.72 (1.73) 0.57 (1.85) 0.06
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VF-MD - visual field mean deviation, VF-PSD - visual field pattern standard deviation, OCT-MD - mean difference between point measurement and age adjusted normative value, OCT-PSD - standard deviation of the mean difference between point measurement and age adjusted normative value

Table 5.

Mean (SD) linear regression slope for subjectively defined VF progressors and non-progressors

VF non-progressors (N = 39) VF-progressors (N = 25) p
VF-MD dB/y 0.07 (0.45) −0.05 (0.64) 0.58
VF-PSD dB/y −0.13 (0.33) 0.08 (0.33) 0.006
OCT mean μm/y −2.14 (4.38) −2.44 (4.34) 0.87
OCT-MD μm/y −1.70 (4.38) −2.00 (4.34) 0.86
OCT-PSD μm/y 0.17 (1.97) 0.74 (1.68) 0.25
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VF-MD - visual field mean deviation, VF-PSD - visual field pattern standard deviation, OCT-MD - mean difference between point measurement and age adjusted normative value, OCT-PSD - standard deviation of the mean difference between point measurement and age adjusted normative value

Table 6.

Mean (SD) linear regression slope stratified by baseline VF-MD

≥ −5dB (N = 53) < −5dB (N = 11) p
VF-MD dB/y 0.02 (0.48) 0.00 (0.73) 0.86
VF-PSD dB/y −0.06 (0.34) 0.03 (0.34) 0.17
OCT mean μm/y −2.40 (4.46) −1.60 (3.78) 0.21
OCT-MD μm/y −1.96 (4.46) −1.16 (3.77) 0.21
OCT-PSD μm/y 0.29 (1.83) 0.90 (2.10) 0.33
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VF-MD - visual field mean deviation, VF-PSD - visual field pattern standard deviation, OCT-MD - mean difference between point measurement and age adjusted normative value, OCT-PSD - standard deviation of the mean difference between point measurement and age adjusted normative value

To determine the possibility of identifying changes using sectoral analysis we reanalyzed the data after grouping the OCT data into four quadrants: superior, temporal, inferior and nasal. The slope for each quadrant was calculated for each parameter after subdividing the group to progressors and non-progressors based on subjective assessment of VF. No significant differences were found between the mean slopes of progressors and non-progressors for any sector.

Discussion

This study evaluated longitudinal morphological RNFL changes as determined by OCT and compared these changes to clinical status as well as to functional glaucoma testing. The results of this study indicate that the rate of RNFL thinning, as determined by OCT, exceeded the rate of functional loss as measured by VF-MD deterioration for all participants (Figure 2).

In evaluating longitudinal changes one should take into account the test-retest variability in repeated measurements. The criteria for progression events used for the K-M survival curve analysis were based on the known reproducibility error of the OCT technology used in this study26 and a chosen cut point for VF-MD.

In setting the cut-off for VF-MD we tried to simulate clinical criteria for progression. We stratified the eyes into progressors and non-progressors based on subjective VF assessment. In this condition, perfect sensitivity and specificity for our objective global VF progression criteria should identify all subjectively chosen progressors as progressing and should find that all non-progressors were stable. The VF-MD that came closest to this was 2 dB (Figure 4, top and bottom). When we liberalized the cut-off to 1 dB, we increased the sensitivity but decreased specificity. Many eyes subjectively identified as stable were called progressors by the objective global criteria at this level. Moreover, the objective criteria, which is based on a global parameter, is not expected to be more sensitive than subjective assessment which takes into account global as well as localized changes in detecting progression. Using a criterion of VF-MD of 4 dB very few subjectively stable eyes were called progressors (Figure 4, top); however, many VF progressors were missed at this threshold (Figure 4, bottom). Thus, VF-MD drop of 2 dB provided the best balance in this setting.

Using these criteria, 2 of the 8 eyes that progressed according to the VF criterion were defined as progressors also by OCT, while 14 eyes progressed by OCT without corresponding VF progression (Figure 3). Similar findings regarding the relationship between structural and functional changes were reported by Kass et al. in the ocular hypertension study (OHTS). In that study, 55% of the subjects reached the predefined end-point criteria of their longitudinal study by ONH progression only, 35% by VF criteria and only 10% by both methods.10 Chauhan et al. reported similar findings with confocal scanning laser ophthalmoscopy (CSLO) where 22 of 25 eyes, from a total of 77 studied eyes, that progressed by VF also progressed by CSLO while 31 eyes progressed by CSLO only.9

When grouping the participating eyes by subjective assessment of VF, K-M analysis showed a significantly greater likelihood of progression by OCT than by VF for those who were classified as VF non-progressors, and there were overlapping curves in the VF progressor group. It should be remembered that the findings of our study for subjective assessment of VF are biased in favor of VF-MD results since the graders were not masked to the global indices results in the VF printouts. The higher rate of RNFL loss in the non-progressor group might reflect hypersensitivity of the OCT or it might reflect true structural changes preceding the appearance of functional changes. This latter explanation is in agreement with previous studies in which a curvilinear relationship was found between functional and structural changes.39–42 One would expect a much larger change to be required initially to manifest a detectable functional change than a structural change (Figure 7). In the midportion of the disease, functional change has a greater slope than structural change, but late in the disease, structural change is again more acute. However, a recent study suggested that there was a linear structural and functional relationship and attributed the curvilinear relationship described above to the logarithmic scaling of VF.43 Further studies are warranted to investigate this relationship.

In order to obtain longitudinal data the study was conducted utilizing data collected from our prototype OCT device. Although this device differs from current commercially available devices in that it has a longer scan time (2.5 seconds) and fewer points per scan (100 A-scans), a previous study showed high correlation between measurements obtained by the prototype device and the commercial OCT 2000 (Pakter HM, Schuman JS, Hertzmark E, et al. Measurement of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography. Unpublished data). Taking into account that OCT devices utilize the same physical principals and the high correlation between measurements obtained by prototype and OCT 2000 devices we believe that the data presented in this study are relevant to the currently available commercial device. The reproducibility of RNFL measurements with the currently available commercial OCT (Stratus OCT, Carl Zeiss Meditec, Dublin, CA) is ~2.5 μm compared to the ~10 μm of the prototype device used in this study (Paunescu LA, Schuman JS, Price LL, et al. Reproducibility of nerve fiber thickness, macular thickness and optic nerve head measurements using third generation commercial optical coherence tomography (Stratus OCT). Submitted to Inves Ophth Vis Sci). The improved reproducibility of Stratus OCT might improve the ability to detect longitudinal structural changes to a greater degree than we found in this study. This warrants further investigation.

Cross-sectional correlation between OCT measures and global VF indices was found to be moderate to good throughout the follow-up period (Table 3). This finding is in agreement with previous studies that found good cross-sectional correlation between OCT and VF findings.11, 32

Linear regression analysis has been used in previous studies to evaluate longitudinal VF changes.44–52 However, due to the large inter-visit VF fluctuation it has been recommended to obtain a large number of VF tests over a long period of follow-up.49, 50 Thus, we required at least 5 VF tests as an inclusion criterion for this study. Most of the participants in the study were familiar with VF testing at the initial study visit. No perimetry learning effect was noted for the remaining participants.

The difference between the likelihood of progression of VF and OCT measures as defined by the linear regression slope stratified by baseline clinical diagnosis was found to be non-significant (Table 4). The difference between likelihood of progression for eyes that were classified as VF progressors and non-progressors was found to be non-significant except for VF-PSD (Table 5). It should be noted that the subjective assessment of the VF was not masked to the global VF indices and thus the results may be biased in favor of VF related parameters. We cannot explain the similarity of these VF-MD curves. Sectoral analysis of OCT results did not yield differences in the likelihood of progression between groups as determined by subjective assessment of VF.

No relationship was found between baseline VF-MD and rate of progression as determined by OCT (Table 6). This finding is in agreement with previous studies where the rate of VF loss was not related to the baseline VF defect.49–51 However, our study was inadequately powered to evaluate this relationship.

Based on our results, the usefulness of linear regression for detection of longitudinal glaucomatous changes with the OCT is questionable. It is possible that glaucoma progression occurs in a non-linear fashion, and that regression is not the most suitable technique for progression detection. The use of OCT-MD and OCT-PSD did not improve the ability to detect change.

In summary, this study longitudinally evaluated OCT peripapillary RNFL measurements and compared these to functional measures as determined by VF and to clinical status. There was a greater likelihood of glaucomatous progression as measured by OCT compared to VF. Our findings suggest that OCT may be a more sensitive indicator than automated perimetry for glaucomatous progression; however, we cannot rule out the possibility that some of the progression identified by OCT represented type-I error. Since there is no gold standard measure of glaucomatous progression, further study of larger populations over longer periods of time will be required to definitively answer this question.

Figure 6.

Figure 6

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Theoretical relationship between structural and functional glaucomatous damage.

Acknowledgments

Supported in part by NIH R01-EY13178-4, RO1-EY11289-16, and P30-EY13078, NSF ECS-0119452, Air Force Office of Scientific Research F49620-01-1-0184, Medical Free Electron Laser Program F49620-01-1-0186, by a grant from the Massachusetts Lions Eye Research Fund Inc., and by Research to Prevent Blindness. G. Wollstein acknowledges support from the American Physician Fellowship for Medicine in Israel.

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