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Optical Coherence Tomography Longitudinal Evaluation of Retinal Nerve Fiber Layer Thickness in Glaucoma Gadi Wollstein, MD 1,2 , Joel S Schuman, MD 1,2 , Lori L Price, MS 3 , Ali Aydin, MD 1 , Paul C Stark, ScD 3 , Ellen Hertzmark, MA 4 , Edward Lai, BSc 1 , Hiroshi Ishikawa, MD 1,2 , Cynthia Mattox, MD 1 , James G Fujimoto, PhD 5 , and Lelia A Paunescu, PhD. 1 1 New England Eye Center, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA 2 UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA 3 Biostatistics Research Center, Division of Clinical Care Research, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA 4 Department of Epidemiology, Harvard School of Public Health, Boston, MA 5 Department of Electrical Engineering and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 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 2μm. 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 Correspondence to: Joel S. Schuman, MD, UPMC Eye Center, University of Pittsburgh School of Medicine, 203 Lothrop Street, The Eye and Ear Institute, Suite 816, Pittsburgh, PA 15213. Tel: 412-647-2205, Fax 412-647-5119, e-mail: [email protected]. Proprietary interest: Drs. Schuman and Fujimoto are inventors of OCT. NIH Public Access Author Manuscript Arch Ophthalmol. Author manuscript; available in PMC 2007 August 9. Published in final edited form as: Arch Ophthalmol. 2005 April ; 123(4): 464–470. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
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Optical coherence tomography (oct) macular and peripapillary retinal nerve fiber layer measurements and automated visual fields

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Page 1: Optical coherence tomography (oct) macular and peripapillary retinal nerve fiber layer measurements and automated visual fields

Optical Coherence Tomography Longitudinal Evaluation ofRetinal Nerve Fiber Layer Thickness in Glaucoma

Gadi Wollstein, MD1,2, Joel S Schuman, MD1,2, Lori L Price, MS3, Ali Aydin, MD1, Paul CStark, ScD3, Ellen Hertzmark, MA4, Edward Lai, BSc1, Hiroshi Ishikawa, MD1,2, CynthiaMattox, MD1, James G Fujimoto, PhD5, and Lelia A Paunescu, PhD.11 New England Eye Center, Tufts-New England Medical Center, Tufts University School of Medicine, Boston,MA

2 UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA

3 Biostatistics Research Center, Division of Clinical Care Research, Tufts-New England Medical Center,Tufts University School of Medicine, Boston, MA

4 Department of Epidemiology, Harvard School of Public Health, Boston, MA

5 Department of Electrical Engineering and Research Laboratory of Electronics, Massachusetts Institute ofTechnology, Cambridge, MA

AbstractObjectives— To longitudinally evaluate optical coherence tomography (OCT) peripapillary retinalnerve fiber layer (RNFL) thickness measurements and to compare RNFL thickness over time toclinical status and automated perimetry.

Methods— Retrospective evaluation of 64 eyes (37 subjects) of glaucoma suspects and glaucomapatients participating in a prospective longitudinal study. All participants had comprehensive clinicalassessment, visual field (VF) testing and OCT scanning every 6 months. Field progression wasdefined 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 2μm.

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 andglaucoma patients was found to be non-significant for all parameters; however, Kaplan-Meiersurvival curve analysis demonstrated a higher progression rate by OCT than by VF. 66% of eyeswere stable throughout the duration of follow-up, 22% progressed by OCT alone, 9% by VF-MDalone and 3% by both VF and OCT.

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

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

In recent years glaucoma imaging modalities were incorporated into the management ofglaucoma patients. These imaging modalities were designed to detect morphological

Correspondence to: Joel S. Schuman, MD, UPMC Eye Center, University of Pittsburgh School of Medicine, 203 Lothrop Street, TheEye and Ear Institute, Suite 816, Pittsburgh, PA 15213. Tel: 412-647-2205, Fax 412-647-5119, e-mail: [email protected] interest: Drs. Schuman and Fujimoto are inventors of OCT.

NIH Public AccessAuthor ManuscriptArch Ophthalmol. Author manuscript; available in PMC 2007 August 9.

Published in final edited form as:Arch Ophthalmol. 2005 April ; 123(4): 464–470.

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glaucomatous abnormalities and might improve the ability to detect longitudinal changesutilizing quantitative measurements. Several cross-sectional studies have demonstrated thecapability 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 capableof obtaining reproducible retinal and nerve fiber layer thickness measurements.26–28 Thisdevice has been shown in cross-sectional studies to allow differentiation between normals andglaucoma 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 standardclinical assessment and automated perimetry.

MethodsData for this study were retrospectively collected from a prospective longitudinal study carriedout 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. Allsubjects attending the service willing to participate in the study and qualified according to thecriteria below were included. Institutional Review Board (IRB) / Ethics Committee approvalwas 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 correctedvisual acuity of 20/60 or better, refractive error between +3.00 to −6.00 diopters and at leastfive reliable VF tests and five good quality OCT scans. The exclusion criteria were: subjectswith a history of diabetes as well as eyes with signs of posterior pole pathology other than thoseattributed to glaucoma or significant media opacity in which the fundus was not visible. Eyesthat underwent cataract extraction or any other intraocular surgery within the period of follow-up were excluded from the study.

Study protocolAll 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 beeligible.

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

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

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

Visual field testingAll patients underwent Humphrey full-threshold 24-2 achromatic perimetry or SwedishInteractive Thresholding Algorithm (SITA) standard 24-2 perimetry. A reliable VF test wasdefined 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 pointsdepressed more than 5 dB or two adjacent points depressed more than 10 dB in the patterndeviation 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 betweenconsecutive visits and between first and last visit. The graders were masked to each other, anyclinical information, date of test and patient age. The graders were asked to grade the changefrom previous VF testing as deterioration, no change or improvement and overall assessmentof change between the first and last VF tests. Consensus between the graders was required incases of disagreement.

Eyes were defined for the analysis as VF progressors by subjective assessment when bothgraders or the consensus agreement, labeled deterioration in the same VF location in 2 of 3consecutive follow-up VFs. All other eyes were classified as VF non-progressors. Eyes weredefined as VF progressors by MD when VF-MD dropped by 2 dB from baseline value in 2 of3 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 eyesthat were tested by both full-threshold and SITA protocols during the follow-up period, theglobal VF indices were treated as a continuum.

OCT scanningOCT is the optical equivalent of B-scan ultrasound where the delay of the backscattered lightfrom the various components of the scanned tissue enables one to differentiate between varioustissue layers. Detailed descriptions of OCT have been previously published.26, 36, 37 OCThas 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 resolutionof 10μm.26 This device acquired 100 circumpapillary measuring points in approximately 2.5seconds. RNFL thickness measurements acquired by this device have been shown to be highlycorrelated 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 andglaucomatous eyes using optical coherence tomography. Unpublished data).

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

Parameters used for the analysis were mean peripapillary RNFL thickness (OCT mean) andtwo new parameters that were computed for this study: OCT mean deviation (OCT-MD) - themean difference between each of the 100 measuring points and age adjusted normative valuesas determined in a previous study (Pakter HM, Schuman JS, Hertzmark E, et al. Measurementof nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence

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tomography. Unpublished data) and OCT pattern standard deviation (OCT-PSD) - the standarddeviation 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 20μm (basedon 2 * reproducibility error of the device26) from the baseline measurement in 2 of 3consecutive follow-up OCT scans.

Statistical analysisThe data were analyzed using SAS software (SAS Institute, Cary, NC). The mixed procedurein 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 testsconducted within 6 months from each other. Linear regression was used to determine the slopeof change for VF and OCT measurements for each eye over time. The group mean slope wasused for the analysis. A significant slope was defined as a slope that significantly differed froma zero slope (p < 0.05).

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

ResultsFifty-five glaucoma eyes (32 subjects) and 9 glaucoma suspect eyes (5 subjects) qualified forthe study. The characteristics of the study population are summarized in Table 1. Within amedian 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).

Baseline VF-MD for the glaucoma suspect group was −0.7 ± 2.1 dB and at last visit −1.1 ± 1.7dB (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 andfinal VF-PSD in neither group. For OCT mean, the initial measure in the glaucoma suspectgroup was 115.7 ± 36.2μm and the last visit 111.3 ± 23.0μm (p = 0.02). In the glaucoma groupthe initial OCT mean was 94.0 ± 21.9μm and the final value was 82.3 ± 25.3μm (p < 0.0001).For both OCT-MD and OCT-PSD the difference between first and last values was significantonly in the glaucoma group.

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

K-M survival curves were used for evaluating time to progression. Overall there was greaterlikelihood of repeatable OCT mean RNFL drop of 20μm compared to VF-MD drop of 2 dBfrom baseline values (p = 0.12) (Figure 2). Altogether, 22/64 eyes were found to progress whenapplying the repeatable VF-MD drop of 2 dB and repeatable OCT drop of 20μm 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 numberof VF progressors (12 eyes OCT only, 15 VF only and 4 both methods) while setting the levelat 4 dB reduced the number (16 eyes OCT only, 1 VF only and none by both methods) (Figure4, top and bottom).

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

Comparing OCT mean and VF-MD for subjects defined as progressors or non-progressors bythe subjective assessment of VF we found a greater likelihood for progression for OCT meancompared 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).

Linear regression analysis was used as an additional method to assess progression. Mean linearregression slopes for the various VF and OCT parameters for the glaucoma suspects andglaucoma patients are summarized in Table 4. The difference in the slope between the groupswas non-significant for all parameters. Stratifying the group based on the subjective assessmentof VF into VF-progressors and VF-non progressors, we found a significant difference only forVF-PSD (Table 5). To investigate the possible effect of baseline VF damage on the rate ofprogression, 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. Thepower to detect a difference between the groups with an alpha = 0.05 was calculated to bebetween 5% and 12% for the various parameters.

To determine the possibility of identifying changes using sectoral analysis we reanalyzed thedata 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 toprogressors and non-progressors based on subjective assessment of VF. No significantdifferences were found between the mean slopes of progressors and non-progressors for anysector.

DiscussionThis study evaluated longitudinal morphological RNFL changes as determined by OCT andcompared these changes to clinical status as well as to functional glaucoma testing. The resultsof this study indicate that the rate of RNFL thinning, as determined by OCT, exceeded the rateof 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 inrepeated measurements. The criteria for progression events used for the K-M survival curveanalysis were based on the known reproducibility error of the OCT technology used in thisstudy26 and a chosen cut point for VF-MD.

In setting the cut-off for VF-MD we tried to simulate clinical criteria for progression. Westratified the eyes into progressors and non-progressors based on subjective VF assessment.In this condition, perfect sensitivity and specificity for our objective global VF progressioncriteria should identify all subjectively chosen progressors as progressing and should find thatall non-progressors were stable. The VF-MD that came closest to this was 2 dB (Figure 4, topand bottom). When we liberalized the cut-off to 1 dB, we increased the sensitivity but decreasedspecificity. Many eyes subjectively identified as stable were called progressors by the objectiveglobal criteria at this level. Moreover, the objective criteria, which is based on a globalparameter, is not expected to be more sensitive than subjective assessment which takes intoaccount 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 of2 dB provided the best balance in this setting.

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Using these criteria, 2 of the 8 eyes that progressed according to the VF criterion were definedas progressors also by OCT, while 14 eyes progressed by OCT without corresponding VFprogression (Figure 3). Similar findings regarding the relationship between structural andfunctional changes were reported by Kass et al. in the ocular hypertension study (OHTS). Inthat study, 55% of the subjects reached the predefined end-point criteria of their longitudinalstudy by ONH progression only, 35% by VF criteria and only 10% by both methods.10Chauhan 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 byCSLO while 31 eyes progressed by CSLO only.9

When grouping the participating eyes by subjective assessment of VF, K-M analysis showeda significantly greater likelihood of progression by OCT than by VF for those who wereclassified as VF non-progressors, and there were overlapping curves in the VF progressorgroup. It should be remembered that the findings of our study for subjective assessment of VFare biased in favor of VF-MD results since the graders were not masked to the global indicesresults in the VF printouts. The higher rate of RNFL loss in the non-progressor group mightreflect hypersensitivity of the OCT or it might reflect true structural changes preceding theappearance of functional changes. This latter explanation is in agreement with previous studiesin 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 detectablefunctional 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, structuralchange is again more acute. However, a recent study suggested that there was a linear structuraland functional relationship and attributed the curvilinear relationship described above to thelogarithmic 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 ourprototype OCT device. Although this device differs from current commercially availabledevices 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 prototypedevice 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 opticalcoherence tomography. Unpublished data). Taking into account that OCT devices utilize thesame physical principals and the high correlation between measurements obtained by prototypeand OCT 2000 devices we believe that the data presented in this study are relevant to thecurrently available commercial device. The reproducibility of RNFL measurements with thecurrently available commercial OCT (Stratus OCT, Carl Zeiss Meditec, Dublin, CA) is~2.5μm compared to the ~10μm of the prototype device used in this study (Paunescu LA,Schuman JS, Price LL, et al. Reproducibility of nerve fiber thickness, macular thickness andoptic nerve head measurements using third generation commercial optical coherencetomography (Stratus OCT). Submitted to Inves Ophth Vis Sci). The improved reproducibilityof Stratus OCT might improve the ability to detect longitudinal structural changes to a greaterdegree than we found in this study. This warrants further investigation.

Cross-sectional correlation between OCT measures and global VF indices was found to bemoderate to good throughout the follow-up period (Table 3). This finding is in agreement withprevious 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 VFchanges.44–52 However, due to the large inter-visit VF fluctuation it has been recommendedto obtain a large number of VF tests over a long period of follow-up.49, 50 Thus, we requiredat least 5 VF tests as an inclusion criterion for this study. Most of the participants in the study

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were familiar with VF testing at the initial study visit. No perimetry learning effect was notedfor the remaining participants.

The difference between the likelihood of progression of VF and OCT measures as defined bythe 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 wereclassified as VF progressors and non-progressors was found to be non-significant except forVF-PSD (Table 5). It should be noted that the subjective assessment of the VF was not maskedto 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 didnot yield differences in the likelihood of progression between groups as determined bysubjective assessment of VF.

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

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

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

Acknowledgements

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

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48. The Glaucoma Laser Trial (GLT); Glaucoma Laser Trial Research Group. Treatment groupdifferences in visual field changes. Am J Ophthalmol 1995;6(120):10–22.

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Figure 1.Difference in time between VF test and OCT scan (months).

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Figure 2.K-M survival curve for VF-MD and OCT mean RNFL for the entire study group.

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Figure 3.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 RNFLthickness drop of 20μm from baseline visit), or both VF and OCT.

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

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Figure 5.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.

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Figure 6.Theoretical relationship between structural and functional glaucomatous damage.

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Table 1Baseline characteristics of study population

Glaucoma Suspect GlaucomaEyes / Subjects 9 / 5 55 / 32Age (SD) yr 50.9 (15.1) 66.6 (14.4)Male / Female 2 / 3 12 / 20Ethnicity (%) Eastern Asian Afro-American Caucasian

005

2 (6.3)7 (21.9)23 (71.9)

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Wollstein et al. Page 18Ta

ble

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Wollstein et al. Page 19Ta

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Table 4Mean (SD) linear regression slope for glaucoma suspects and glaucoma patients

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

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Table 5Mean (SD) linear regression slope for subjectively defined VF progressors and non-progressors

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

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Table 6Mean (SD) linear regression slope stratified by baseline VF-MD

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

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