Measurement of Local Retinal Ganglion Cell Layer Thickness in Patients with Glaucoma Using Frequency-Domain Optical Coherence Tomography

CLINICAL SCIENCES Measurement of Local Retinal Ganglion Cell Layer Thickness in Patients With Glaucoma Using Frequency-Domain Optical Coherence Tomography

Min Wang, MD; Donald C. Hood, PhD; Jung-Suk Cho; Quraish Ghadiali, BA; Gustavo V. De Moraes, MD; Xian Zhang, PhD; Robert Ritch, MD; Jeffrey M. Liebmann, MD

Objective: To explore the feasibility of obtaining a significantly thinner than those of the high-sensitivity local measurement of the thickness of the retinal gan- group. While these layers were thinner in the patients glion cell layer in patients with glaucoma using than the controls, the thicknesses of inner nuclear frequency-domain optical coherence tomography layer and receptor layer were similar in all 3 groups. (fdOCT) and a computer-aided manual segmentation Further, the thinning of the retinal ganglion cell plus procedure. inner plexiform layer in 1 glaucoma-affected eye showed qualitative correspondence to the loss in 10-2 Methods: The fdOCT scans were obtained from the hori- visual field sensitivity. zontal midline for 1 eye of 26 patients with glaucoma and 20 control subjects. The thickness of various layers was Conclusions: Local measures of RGC layer thickness measured with a manual segmentation procedure aided by can be obtained from fdOCT scans using a manual a computer program. The patients were divided into low- segmentation procedure, and these measures show and high-sensitivity groups based on their foveal sensitiv- qualitative agreement with visual field sensitivity. ity on standard automated perimetry.

Results: The RGC plus inner plexiform and the retinal nerve fiber layers of the low-sensitivity group were Arch Ophthalmol. 2009;127(7):875-881

LAUCOMA DAMAGES RETI- many individuals and do not necessarily nal ganglion cells (RGCs) describe a particular individual. For ex- and their axons, leading ample, Garway-Heath et al4 pointed out to characteristic changes that the 95% confidence interval for the in the structure of the op- location on the disc of the projections from ticG disc and in visual fields as measured a particular SAP point is almost 30°. In- with standard automated perimetry (SAP). dividual variation in this map is probably Author Affiliations: In an attempt to understand how func- a major contributor to the large intersub- Departments of Psychology tional losses (eg, local loss of visual field ject variability seen in plots of tdOCT (Drs Wang, Hood, and Zhang, sensitivity) relate to the structural dam- RNFL loss vs loss in visual field.5 Ms Cho, and Mr Ghadiali) and age (eg, loss of RGCs and their axons), If reliable measures of local RGC Ophthalmology (Dr Hood), many studies have measured visual loss layer thickness can be obtained, it might Columbia University, New York, New York; Einhorn Clinical with SAP and structural damage with time- be possible to decrease the variability in Research Center, New York Eye domain optical coherence tomography the structure vs function plots. With the and Ear Infirmary (tdOCT).1-3 With tdOCT, the thickness of newer frequency-domain (fd)–OCT, the (Drs De Moraes, Ritch, and the axon layer (ie, the retinal nerve fiber RGC layer, or at least the combined Liebmann), New York, New layer [RNFL]) is measured as it enters the RGC and inner plexiform layers (IPL), York; and the Department of optic nerve head. Therefore, to compare can be visualized. Here we use fdOCT Ophthalmology and Visual local changes in this structural measure to measure the RGC/IPL and RNFL Science, Shanghai Medical School, Eye, Ear, Nose, and with local functional losses in sensitivity, along the horizontal meridian. We Throat Hospital, Fudan a map relating the field position to the op- chose to study the horizontal meridian University, Shanghai, China tic disc sector must be assumed. While for 2 reasons. First, it includes the (Dr Wang). these maps exist, they are averaged for fovea, the most important structure for

(REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 7), JULY 2009 WWW.ARCHOPHTHALMOL.COM 875

©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 detailed vision and a possible site of undetected glau- glaucomatous optic neuropathy, or uveitis were excluded comatous damage. Second, the horizontal meridian from this study. includes the papillomacular bundle, which consists of Twenty eyes of 20 control subjects (mean [SD] age, the axons of the RGCs nasal to the fovea and thus the 51.4[9.4] years) had best-corrected visual acuity of axons that travel directly to the optic disc. Conse- 20/25 or better, with no history of elevated intraocular pressure and a normal visual field on SAP. Control eyes had quently, the region between the fovea and the optic a normal-appearing optic disc evaluated by fundus disc is a place in the retina where the loss in visual examination. field sensitivity should be reflected in both local RGC Written informed consent was obtained from all partici- loss and local RNFL loss. pants. Procedures followed the tenets of the Declaration of The main purpose of this study was to explore the Helsinki, and the protocol was approved by the committee of feasibility of obtaining a measure of the local thickness the institutional board of research associates of Columbia of the RGC layer. A computer-aided manual segmenta- University. tion technique was used to measure local RGC/IPL (RGCϩ) thickness as well as the thickness of the receptor layer, the inner nuclear layer (INL), and the RNFL. OCT SCANS The results for controls with healthy vision were compared with those of a group of patients with a range of Subjects had fdOCT scans of the horizontal meridian (3D- glaucomatous damage to the macular region. The feasi- OCT 1000; Topcon Corporation, Tokyo, Japan). These were bility of using these measures to study the relation of horizontal line scans, which consisted of 1024 A-scans 6 mm structural damage of the macular to functional damage in length (overlapping set at 16) and/or the midline scan of a was also considered. volume scan, which covered a 6ϫ6 mm area with 512ϫ128 A-scans in density. Figure 1A shows the location of the ϫ METHODS 6 6–mm region and the single horizontal line scan. Scan protocols were repeated 3 times, and the best quality horizontal scan was chosen for segmentation. SUBJECTS The OCT files were exported to a program written in Mat- lab 7.4 (MathWorks, Natick, Massachusetts) for segmenta- Twenty-six eyes of 26 patients with glaucoma (mean [SD] tion. The operator, one of the authors (M.W. or J.-S.C.), age, 60.5[12.7] years) were included in this study. Each masked to the status of the visual field, manually marked the patient received a complete ophthalmic examination includ- borders of 5 retinal layers, and the program used a spline ing medical history review, best-corrected visual acuity, slit- interpolation algorithm to determine the border.6 The number lamp biomicroscope, intraocular pressure measurement with of points needed to define the boundary depended on the cur- Goldmann applanation tonometry, dilated funduscopic vature of the boundary and ranged between 3 and 10. Essen- examination, gonioscopy, and SAP with the Humphrey Field tially flat boundaries (eg, some choroid borders) needed only Analyzer II (Carl Zeiss Meditec Inc, Dublin, California) using 3 points to be described, while curved boundaries (eg, the the 24-2 program and the Swedish Interactive Threshold vitreous/RNFL border) required up to 10. The segmentation Algorithm. Inclusion criteria for these patients included best- boundaries were confirmed by another author (D.C.H.) who corrected visual acuity of 20/60 or better, spherical refraction was also experienced in segmenting OCT scans and masked within ±6.00 diopters (D), cylinder correction within ±2.00 D, to the status of the visual field. In particular, if the second per- and open angle on gonioscopy. In addition, all eyes had glau- son disagreed with a particular segmentation, the 2 operators comatous damage, as indicated by glaucomatous optic neu- discussed the points of disagreement and, in all but 1 case, ropathy and an abnormal 24-2 visual field (abnormal glau- agreed on the correct segmentation. In the 1 exception, the coma hemifield test and/or abnormal mean deviation [MD]). senior author adjudicated the final decision. We have previ- Glaucomatous optic neuropathy was defined as a vertical cup ously shown that there is good interobserver agreement.6 In to disc ratio greater than 0.6, asymmetry of the cup to disc particular, the concordance correlation coefficients between ratio 0.2 or greater between eyes, presence of localized RNFL, observers averaged 0.95 or better for the 2 layers of primary or neuroretinal rim defects or a splinter hemorrhage in the interest here (RNFL and RGCϩ) for both patients and absence of any other abnormalities that could explain such controls.6 findings. Patients with clinically significant cataracts, other The 5 borders that were marked (Figure 1B) were media opacities, or other ocular diseases were excluded. For (1) the border between the vitreous and the RNFL, 23 of the 26 patients, the eye chosen for analysis had the (2) the border between the RNFL and the RGC, (3) the bor- worse MD value. In one case, the eye with the worse MD had der between the IPL and the INL, (4) the border between the an unreliable field; in a second case, the eye had a poor OCT INL and outer plexiform layer, and (5) the border between scan; and in the third case, the 2 eyes had nearly identical the Bruch membrane and the choroid. Using these borders, MDs, so the one with the poorer central sensitivity was cho- the thickness of 4 layers was calculated. In particular, the sen. The patients were placed into 2 groups based on their RNFL thickness was calculated as the difference between sensitivity to the foveal test point in the 24-2 visual field. Sev- borders 1 (vitreous/RNFL border) and 2 (RNFL/RGC border). enteen patients had a foveal sensitivity within normal limits Similarly, the RGC layer plus IPL (RGCϩ) was the difference and comprised the high-sensitivity group. The other 9 between borders 2 and 3. Because the border between RGC patients, the low-sensitivity group, had abnormal foveal sensi- and IPL could not be differentiated on most scans, we tivity. The average foveal sensitivities were 35.9 dB (range, measured the combined thickness as RGCϩ. In addition, the 33-39 dB) and 27.9 dB (range, 23-32 dB) for the high- and INL thickness was calculated as the difference between low-sensitivity groups, respectively. The average of the MD borders 4 and 5, and the receptorϩ thickness (RECϩ, for the 24-2 visual field was −7.0 dB (range, −0.7 to −25.4 dB) which included the outer plexiform layer, photoreceptor and −13.3 dB (range, −3.6 to −26.6 dB) for the high- and low- layer, retinal pigment epithelium, and Bruch membrane) sensitivity groups, respectively. Eyes with retinal disease, non- as5to6.

(REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 7), JULY 2009 WWW.ARCHOPHTHALMOL.COM 876

B INL + RGC RNFL

1. Vitreous/RNFL

2. RNFL/RGC 3. IPL/INL 4. INL/OPL

REC + 5. BM/choroid

Figure 1. The frequency-domain optical coherence tomographic scan location and segmentation technique. A, The location of the 6ϫ6–mm (gray) scan volume and the single horizontal line scan (green) are superimposed on a fundus image. B, A horizontal line scan of one of the controls shows the 5 borders determined as part of the computer-aided segmentation technique. They are (1) red, the border between the vitreous and the retinal nerve fiber layer (RNFL); (2) orange, the border between the RNFL and the retinal ganglion cell layer (RGC); (3) green, the border between the inner plexiform layer (IPL) and the inner nuclear layer (INL); (4) light blue, the border between the INL and outer plexiform layer (OPL); and (5) violet, the border between the Bruch membrane (BM) and the choroid. RECϩ indicates receptor and OPL layers. C, A horizontal line scan of a patient with glaucoma shows loss of the RNFL and RGC layer.

RESULTS fall largely within the 95% confidence intervals for the controls. The RNFL (Figure 3A) and RGCϩ (Figure 3B) data show a range of thicknesses, including many curves RETINAL LAYERS ALONG with portions of their thickness curves falling below the THE HORIZONTAL MERIDIAN 95% confidence intervals. The 26 patients were divided into 2 groups based on Figure 2 contains the thickness profiles along the horizontal meridian (Figure 2A) for each of the 20 controls the foveal sensitivity obtained with the 24-2 visual field and for each of the 4 retinal layers. The mean (2 SD) and test. Figure 4 compares the curves for the mean (1 stan- 95% confidence intervals are indicated by the bold black dard error [SE]) for the patient groups with high and low curves. The results here and in Figures 2-4 are pre- foveal sensitivity with those for the controls. The curves sented as if all eyes were right eyes. That is, the data for (mean [1 SE]) for the outer retinal layers (Figure 4,C ϩ left eyes were plotted right to left. and D; INL and REC ) of the 2 groups of patients are The data from the controls qualitatively match what indistinguishable from each other and from the curves is expected owing to known anatomy. The RECϩlayer for the controls. However, the RNFL and RGC curves for (panel Figure 2D) is thickest in the center of the fovea; the high-sensitivity group fell below those of the con- the INL (Figure 2C) and RGCϩ (Figure 2B) approach trols, while those of the low-sensitivity group fell well zero in the center and peak in the perifovea; and the below both the curves for the controls and the high- RNFL (Figure 2A) is near zero on the temporal side of sensitivity group. the fovea and increases on the nasal side as the optic To test the significance of the differences between disc is approached. In principle, the RNFL should not groups, the average thickness for each layer and each in- exist along the horizontal meridian in the temporal dividual was calculated; the means (standard devia- retina. The measurements here are probably influ- tions) of these average thicknesses are shown in the Table. enced by a number of factors, including local thicken- As expected from Figure 4, C and D, there was no sig- ing of the internal limiting membrane and axons that nificant difference (pairwise t tests) between any of the either cross the midline and/or are present owing to groups for the INL and RECϩ layers. On the other hand, small errors in the placement of the horizontal both patient groups had significantly thinner layers than meridian. the controls for the RNFL (high P=.03; low PϽ.001) and Figure 3 shows the results for the 26 patients. The RGCϩ layer (PϽ.001 for both high and low groups). In INL (Figure 3C) and RECϩ (Figure 3D) thickness curves addition, the low-sensitivity group had significantly thin-

(REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 7), JULY 2009 WWW.ARCHOPHTHALMOL.COM 877

0.15 0.15

0.10 0.10 Temporal retina Nasal retina

0.05 0.05

0.00 0.00

C D Thickness, mm

0.15 0.30

0.25

0.10 0.20

0.15

0.05 0.10

0.05

0.00 0.00

– 2 – 1 0 1 2 3 – 2 – 1 0 1 2 3 Distance From Foveal Center, mm

Figure 2. The thickness profiles for individual controls (colored curves) for the retinal nerve fiber layer (A), retinal ganglion cell ϩ inner plexiform layer (B), inner nuclear layer (C), and receptorϩouter plexiform layer (D). The mean limits (2 SD) are indicated by the bold black curves.

ner layers than the high group for both the RNFL COMMENT (PϽ.001) and RGC layer (PϽ.003).

LOCAL RGC؉ LOSS VS VISUAL FIELD LOSS A computer-aided manual segmentation technique was used IN A SINGLE PATIENT to measure the thickness of retinal layers seen in fdOCT scans of patients with glaucoma and control subjects. While Our objective here was not to make a quantitative com- 2 previous studies6,7 used a similar approach to study the parison of local RGCϩ thickness to local visual field sen- thickness of retinal layers in patients with diseases of the sitivity. The 24-2 field has too few points for a careful com- outer retina, our interest was in the thickness of the RGCϩ parison, and we only segmented the scan along the layer and RNFL of patients with glaucoma. In particular, horizontal meridian. However, to test the feasibility of such we asked whether it was feasible to obtain local measures a comparison, we obtained a 10-2 visual field test on 1 pa- of RGCϩ and RNFL thickness and whether these mea- tient. Figure 5 shows the 10-2 total deviation field of the sures might be associated with local glaucomatous loss. In left eye from this patient, along with the scan images from general, the results are encouraging. the 6ϫ6–mm volume scan that correspond to the hori- First, we confirmed that the local thickness of the 4 lay- zontal lines of test points in the 10-2 test. In general, the ers measured were consistent with known retinal anatomy patient’s RGCϩ layer thickness is markedly thinner than for the controls and for the patients. For example, in the that of an age-matched control in the locations of the vi- controls, the RGCϩ layers showed maxima in thickness sual field with large losses in sensitivity. just outside the fovea, while the RNFL increased in thick-

(REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 7), JULY 2009 WWW.ARCHOPHTHALMOL.COM 878

0.15 0.15

0.10 0.10 Temporal retina Nasal retina

0.05 0.05

0.00 0.00

C D Thickness, mm

0.15 0.30

0.25

0.10 0.20

0.15

0.05 0.10

0.05

0.00 0.00

– 2 – 1 0 1 2 3 – 2 – 1 0 1 2 3 Distance From Foveal Center, mm

Figure 3. The thickness profiles for individual patients (colored curves) for the retinal nerve fiber layer (A), retinal ganglion cell ϩ inner plexiform layer (B), inner nuclear layer (C), and receptorϩouter plexiform layer (D). The mean limits (2 SD) for the controls from Figure 2 are indicated by the bold black curves.

ness between the foveal center and the optic disc. As ex- Finally, we presented evidence that it might be pos- pected, both of these layers were decreased in thickness in sible to compare local sensitivity with local RGCϩ loss some of the patients with glaucoma. quantitatively. To test the feasibility of comparing the lo- Second, to see if the changes in the RGCϩ and RNFL cal loss of visual field sensitivity (ie, functional loss) with layers corresponded, in general, with the loss of visual the loss of RGCs and their axons (ie, structural damage), function, the thickness of the RGCϩ and RNFL layers we compared the RGCϩ layer thickness with 10-2 visual in patients with low (abnormal) foveal sensitivity were field loss in 1 glaucomatous eye. The loss of visual field sen- compared with the thickness in patients with high (nor- sitivity appeared to correspond to the thinning of RGCϩ mal) foveal sensitivity. We found that the RGC layer and layer (Figure 5). The limitation of this example is a lack of RNFL of the low-sensitivity group were significatly thin- a true control group. A careful quantitative comparison of ner than in the high-sensitivity group. While these lay- a large group of patients is needed, and this comparison ers were significantly thinner in both patient groups com- will require consideration of the displacement of the RGC pared with the control subjects, the thickness of the INL relative to the location of the receptors feeding into them.9 and RECϩlayers were similar for all 3 groups. In gen- Although algorithms have been proposed for segment- eral, these results are consistent with an earlier study8 ing the RGC layer (eg, references8,10,11 and RTuve software; that found that the average thickness of the macular RNFL Optovue, Fremont, California), as far as we know there is and the RGCϩ layer were significantly thinner than in no algorithm available in the public domain for analyzing controls, although we did not find, as they did, any evi- images from any fdOCT machine. However, it is possible dence of abnormal thickening in the receptor region to obtain a measure of local RGC thickness without the need (RECϩ). of a computer algorithm.6 Using this manual segmentation

(REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 7), JULY 2009 WWW.ARCHOPHTHALMOL.COM 879

0.10 0.10 Temporal retina Nasal retina

0.05 0.05

0.00 0.00

C D Thickness, mm

0.15

0.2

0.10

0.1 0.05

0.00 0.0

– 2 – 1 0 1 2 3 – 2 – 1 0 1 2 3 Distance From Foveal Center, mm

Figure 4. The mean thickness profiles (1 SE) for the controls, patients with high central sensitivity, and patients with low sensitivity for the retinal nerve fiber layer (A), retinal ganglion cellϩ inner plexiform layer (B), inner nuclear layer (C), and receptorϩouter plexiform layer (D).

Table. Mean Thickness of the 4 Layers for the Controls and the High- and Low-Sensitivity Groups

Mean (SD) Thickness, µm

RNFL RGC؉ INL REC؉ Controls (n=20) 14.1 (1.5) 74.8 (5.1) 31.1 (3.4) 181.3 (8.9) High sensitivity (n=17) 11.6 (4.7) 61.1 (7.1) 31.5 (3.6) 181.1 (8.4) Low sensitivity (n=9) 4.8 (3.1) 50.4 (9.1) 31.9 (2.8) 182.7 (6.6)

Abbreviations: INL, inner nuclear layer; RECϩ, receptor ϩ outer plexiform layer; RGCϩ, retinal ganglion cell ϩ inner plexiform layer; RNFL, retinal nerve fiber layer.

procedure, we found that the reduction in thickness of the rich in RGCs, it has been suggested that glaucomatous dam- RGClayershowedaqualitativecorrespondencetolocallosses age of this central region might occur early in the disease in visual field sensitivity. While it remains for future stud- process. In fact, monkey models of glaucoma show signifi- ies to determine how good this correspondence actually is, cant loss of macular RGCs.12,13 However, in general, OCT our findings suggest that the RGCϩ layer can be measured measures of the macular region have not outperformed mea- in the macular region using commercially available scans. sures of peripapillary RNFL thickness in detecting glauco- These findings also have possible implications for early de- matous damage.14-18 On the other hand, these OCT studies tection of macular damage. Because the macular region is measured total macular thickness, not RGC thickness. It re-

(REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 7), JULY 2009 WWW.ARCHOPHTHALMOL.COM 880

7°

1°

3° – 30 – 13 – 10 – 13 – 16 – 1– 4 – 20 – 20 – 12 – 23 – 34 – 26 – 6– 2 – 13 – 3– 3– 4– 12 – 35 – 30 – 4 0° – 30– 1– 11– 4– 30 – 26– 4 – 2 – 20– 1– 10– 1– 1– 20– 1 – 3° 0– 21– 1– 1000 – 2– 1– 2– 1– 1– 1– 1– 1 – 2– 2– 2– 10– 1 – 1° – 3– 1

– 7°

0.12 – 5° 0.08

mm 0.04 Thickness, 0.00 – 3 – 2 – 1 0 1 2 3 Distance From Fovea, mm

Figure 5. The 10-2 total deviation of visual field (center) of the left eye of a patient with glaucoma. The scan images (left and right) are from the 6ϫ6–mm volume scan and correspond to the horizontal lines of the test points in the 10-2, as shown by the black lines. The segmentation borders of the retinal ganglion cell ϩ inner plexiform layer (RGCϩ) are shown by orange and green curves. The thickness of the RGCϩ layer (distance between the orange and green borders) is shown as red curves in the accompanying graph, with the thickness from a single control of a similar age shown in blue.

mains to be seen how sensitive a direct measure of the RGC sual field to the optic disc in normal tension glaucoma eyes. Ophthalmology. 2000; 107(10):1809-1815. layer, as used here, will be in detecting early glaucomatous 5. Hood DC, Anderson SC, Wall M, Kardon RH. Structure versus function in glau- damage. coma: an application of a linear model. Invest Ophthalmol Vis Sci. 2007;48 (8):3662-3668. 6. Hood DC, Lin CE, Lazow MA, Locke KG, Zhang X, Birch DG. Thickness of receptor Submitted for Publication: November 18, 2008; final re- and post-receptor retinal layers in patients with retinitis pigmentosa measured with vision received February 27, 2009; accepted March 27, 2009. frequency-domain optical coherence tomography (fdOCT) [published online No- Correspondence: Donald C. Hood, PhD, Department of vember 14, 2008]. Invest Ophthalmol Vis Sci. doi:10.1167/iovs.08-2936. 7. Lim JI, Tan O, Fawzi AA, Hopkins JJ, Gil-Flamer JH, Huang D. A pilot study of Psychology, Columbia University, 1190 Amsterdam Ave, fourier-domain optical coherence tomography of retinal dystrophy patients. Am 301 Schermerhorn Hall, New York, NY 10027 (dch3 J Ophthalmol. 2008;146(3):417-426. @columbia.edu). 8. Ishikawa H, Stein DM, Wollstein G, Beaton S, Fujimoto JG, Schuman JS. Macu- lar segmentation with optical coherence tomography. Invest Ophthalmol Vis Sci. Financial Disclosure: Drs Hood and Liebmann report 2005;46(6):2012-2017. being consultants for Topcon, Inc; no other authors re- 9. Drasdo N, Millican CL, Katholi CR, Curcio CA. The length of Henle fibers in the port financial disclosures. human retina and a model of ganglion receptive field density in the visual field. Vision Res. 2007;47(22):2901-2911. Funding/Support:Thisstudywassupportedinpartbygrants 10. Fernandez DC, Salinas HM, Puliafito CA. Automated detection of retinal layer struc- EY09076andEY02115fromtheNationalInstitutesofHealth, tures on optical coherence tomography images. Opt Express. 2005;13(25): Bethesda,Maryland;theShelleyandStevenEinhornResearch 10200-10216. 11. Garvin MK, Abramoff MD, Kardon R, Russell SR, Wu X, Sonka M. Intraretinal FundoftheNewYorkGlaucomaResearchInstitute;andTop- layer segmentation of macular optical coherence tomography images using op- con, Inc; Dr Wang was supported in part by grant of timal 3-D graph search. IEEE Trans Med Imaging. 2008;27(10):1495-1505. 2007CB512204 from the National Basic Research Program 12. Glovinsky Y, Quigley HA, Pease ME. Foveal ganglion cell loss is size dependent in experimental glaucoma. Invest Ophthalmol Vis Sci. 1993;34(2):395-400. of China and by grants 30571996 and 30600696 from the 13. Frishman LJ, Shen FF, Du L, et al. The scotopic electroretinogram of macaque National Science Foundation of China. after retinal ganglion cell loss from experimental glaucoma. Invest Ophthalmol Role of the Sponsor: Topcon, Inc, supplied the ocular Vis Sci. 1996;37(1):125-141. 14. Leung CK, Chan WM, Yung WH, et al. Comparison of macular and peripapillary coherence tomography machines used in this study. measurements for the detection of glaucoma: an optical coherence tomography study. Ophthalmology. 2005;112(3):391-400. REFERENCES 15. Sa´nchez-Galeana CA, Bowd C, Zangwill LM, Sample PA, Weinreb RN. Short- wavelength automated perimetry results are correlated with optical coherence tomography retinal nerve fiber layer thickness measurements in glaucomatous 1. Garway-Heath DF. Comparison of structural and functional methods: I. In: Wein- eyes. Ophthalmology. 2004;111(10):1866-1872. reb RN, Greve EL, eds. Glaucoma Diagnosis: Structure and Function. The Hague, 16. Budenz DL, Michael A, Chang RT, McSoley J, Katz J. Sensitivity and specificity of the Netherlands: Kugler Publications; 2004:135-143. the StratusOCT for perimetric glaucoma. Ophthalmology. 2005;112(1):3-9. 2. Bowd C, Zangwill LM, Medeiros FA, et al. Structure-function relationships using 17. Nouri-Mahdavi K, Hoffman D, Tannenbaum DP, Law SK, Caprioli J. Identifying confocal scanning laser ophthalmoscopy, optical coherence tomography, and early glaucoma with optical coherence tomography. Am J Ophthalmol. 2004; scanning laser polarimetry. Invest Ophthalmol Vis Sci. 2006;47(7):2889-2895. 137(2):228-235. 3. Hood DC, Kardon RH. A framework for comparing structural and functional mea- 18. Kanadani FN, Hood DC, Grippo TM, et al. Structural and functional assessment sures of glaucomatous damage. Prog Retin Eye Res. 2007;26(6):688-710. of the macular region in patients with glaucoma. Br J Ophthalmol. 2006;90 4. Garway-Heath DF, Poinoosawmy D, Fitzke FW, Hitchings RA. Mapping the vi- (11):1393-1397.

(REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 7), JULY 2009 WWW.ARCHOPHTHALMOL.COM 881

©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 Submitted for Publication: January 7, 2010; final revi- 10. Wolfensberger TJ. The role of carbonic anhydrase inhibitors in the management sion received February 26, 2010; accepted March 4, 2010. of macular edema. Doc Ophthalmol. 1999;97(3-4):387-397. 11. Cox SN, Hay E, Bird AC. Treatment of chronic macular edema with acetazolamide. Correspondence: Gerald A. Fishman, MD, Department Arch Ophthalmol. 1988;106(9):1190-1195. of Ophthalmology and Visual Sciences, Eye and Ear 12. Fishman GA, Gilbert LD, Fiscella RG, Kimura AE, Jampol LM. Acetazolamide for Infirmary, Room 3.85, 1855 W Taylor St, MC 648, treatment of chronic macular edema in retinitis pigmentosa. Arch Ophthalmol. Chicago, IL 60612-7234 ([email protected]). 1989;107(10):1445-1452. Author Contributions: Drs Genead and Fishman had full 13. Grover S, Fishman GA, Fiscella RG, Adelman AE. Efficacy of dorzolamide hydro- chloride in the management of chronic cystoid macular edema in patients with access to all of the data in the study and take responsi- retinitis pigmentosa. Retina. 1997;17(3):222-231. bility for the integrity of the data and the accuracy of the 14. Apushkin MA, Fishman GA, Grover S, Janowicz MJ. Rebound of cystoid macu- data analysis. lar edema with continued use of acetazolamide in patients with retinitis pigmentosa. Financial Disclosure: None reported. Retina. 2007;27(8):1112-1118. Funding/Support: This work was supported by the Foun- 15. Fishman GA, Glenn AM, Gilbert LD. Rebound of macular edema with continued dation Fighting Blindness, Owings Mills, Maryland; Grant use of methazolamide in patients with retinitis pigmentosa. Arch Ophthalmol. 1993;111(12):1640-1646. Healthcare Foundation, Lake Forest, Illinois; core grant 16. Fishman GA, Apushkin MA. Continued use of dorzolamide for the treatment of EYO1792 from the National Institutes of Health, Bethesda, cystoid macular edema in patients with retinitis pigmentosa. Br J Ophthalmol. Maryland; and an unrestricted departmental grant from 2007;91(6):743-745. Research to Prevent Blindness, New York, New York. 17. Genead MA, Fishman GA, Walia S. Efficacy of sustained topical dorzolamide therapy Online-Only Material: The eTables are available at http: for cystic macular lesions in patients with X-linked retinoschisis. Arch Ophthalmol. 2010;128(2):190-197. //www.archophthalmol.com. 18. Grover S, Apushkin MA, Fishman GA. Topical dorzolamide for the treatment of cystoid macular edema in patients with retinitis pigmentosa. Am J Ophthalmol. REFERENCES 2006;141(5):850-858. 19. Chan A, Duker JS, Ko TH, Fujimoto JG, Schuman JS. Normal macular thickness measurements in healthy eyes using Stratus optical coherence tomography. Arch 1. Marmor MF, Aguirre G, Arden GB, et al. Retinitis pigmentosa: a symposium on ter- Ophthalmol. 2006;124(2):193-198. minology and methods of examination. Ophthalmology. 1983;90(2):126-131. 20. Grover S, Fishman GA, Gilbert LD, Anderson RJ. Reproducibility of visual acuity 2. Rosenberg T, Haim M, Hauch AM, Parving A. The prevalence of Usher syn- measurements in patients with retinitis pigmentosa. Retina. 1997;17(1): drome and other retinal dystrophy–hearing impairment associations. Clin Genet. 33-37. 1997;51(5):314-321. 3. Walia S, Fishman GA, Hajali M. Prevalence of cystic macular lesions in patients 21. Greenstein VC, Holopigian K, Siderides E, Seiple W, Carr RE. The effects of ac- with Usher II syndrome. Eye (Lond). 2009;23(5):1206-1209. etazolamide on visual function in retinitis pigmentosa. Invest Ophthalmol Vis Sci. 4. Hajali M, Fishman GA. The prevalence of cystoid macular edema on optical co- 1993;34(1):269-273. herence tomography in retinitis pigmentosa patients without cystic changes on 22. Marmor MF, Abdul-Rahim AS, Cohen DS. The effect of metabolic inhibitors on fundus examination. Eye (Lond). 2009;23(4):915-919. retinal adhesion and subretinal fluid resorption. Invest Ophthalmol Vis Sci. 1980; 5. Fetkenhour CL, Choromokos E, Weinstein J, Shoch D. Cystoid macular edema 19(8):893-903. in retinitis pigmentosa. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol. 23. Tsuboi S, Pederson JE. Experimental retinal detachment, X: effect of acetazol- 1977;83(3, pt 1):OP515-OP521. amide on vitreous fluorescein disappearance. Arch Ophthalmol. 1985;103(10): 6. Fishman GA, Fishman M, Maggiano JM. Macular lesions associated with retini- 1557-1558. tis pigmentosa. Arch Ophthalmol. 1977;95(5):798-803. 24. Kawasaki K, Mukoh S, Yonemura D, Fujii S, Segawa Y. Acetazolamide-induced 7. Ffytche TJ. Cystoid maculopathy in retinitis pigmentosa. Trans Ophthalmol Soc changes of the membrane potentials of the retinal pigment epithelial cell. Doc UK. 1972;92:265-283. Ophthalmol. 1986;63(4):375-381. 8. Wolfensberger TJ, Aptsiauri N, Godley B, Downes S, Bird AC. Antiretinal anti- 25. London NJS, Fung AE. Evaluating the nerve and macular thickness measure- bodies associated with cystoid macular edema [in German]. Klin Monatsbl ments of the Optovue RTVue, Zeiss Stratus, and Cirrus OCTs [e-abstract 4241]. Augenheilkd. 2000;216(5):283-285. Invest Ophthalmol Vis Sci. 2008;49:A334. 9. Fishman GA, Gilbert LD, Anderson RJ, Marmor MF, Weleber RG, Viana MA. 26. Fullerton JM, Kim JE, Xiang Q, Szabo A. Comparison of spectral domain OCT Effect of methazolamide on chronic macular edema in patients with retinitis and time domain OCT for measurements of retinal thickness [e-abstract 1073]. pigmentosa. Ophthalmology. 1994;101(4):687-693. Invest Ophthalmol Vis Sci. 2009;50:D1017.

Correction

Error in Byline. In the Clinical Sciences article titled “Measurement of Local Retinal Ganglion Cell Layer Thickness in Patients With Glaucoma Using Frequency- Domain Optical Coherence Tomography” by Wang et al, published in the July 2009 issue of the Archives (2009; 127(7):875-881), there was an error in the byline. The name Gustavo V. De Moraes, MD, should have appeared as Carlos Gustavo De Moraes, MD.

(REPRINTED) ARCH OPHTHALMOL / VOL 128 (NO. 9), SEP 2010 WWW.ARCHOPHTHALMOL.COM 1150