Patterns of Damage in Chronic Angle-Closure Glaucoma Compared to Primary Open-Angle Glaucoma

Patterns of Damage in Chronic Angle-Closure Glaucoma Compared to Primary Open-Angle Glaucoma KOUROS NOURI-MAHDAVI, CHUTIMA SUPAWAVEJ, ELENA BITRIAN, JOANN A. GIACONI, SIMON K. LAW, ANNE L. COLEMAN, AND JOSEPH CAPRIOLI ● PURPOSE:

To compare patterns of damage in chronic angle-closure glaucoma (CACG) to a control group of patients with primary open-angle glaucoma (POAG). ● DESIGN: Retrospective cross-sectional study. ● METHODS: SETTING: Academic tertiary-care glaucoma clinic. STUDY POPULATION: Thirty-two eyes of 32 patients with CACG and good-quality Heidelberg Retina Tomograph (HRT) images (pixel standard deviation <50 ␮m) and stereoscopic disc photographs within 1 year of a visual field showing reproducible glaucomatous field loss (mean deviation >ⴚ15.0 dB) were enrolled. Control eyes with POAG meeting similar criteria and matched for severity of field loss (ⴞ1 dB) and race were selected. OUTCOME MEASURES: Presence of focal rim loss (<1 clock hour), HRT stereometric parameters, and extent and location of field loss. ● RESULTS: The average mean deviation was ⴚ5.1 dB in both groups. Patients with CACG were more hyperopic (0.6 ⴞ 0.4 vs ⴚ1.4 ⴞ 0.5 D; P < .001) and had higher IOP at the time of imaging (15.8 ⴞ 0.8 vs 13.9 ⴞ 0.9 mm Hg; P ⴝ .015). Focal disc damage was not less frequent in PACG eyes (19% vs 24%; P ⴝ .545). Eyes with PACG had smaller cup area, cup volume, and mean cup depth and larger rim/disc area ratio (P < .05 for all), which persisted after adjusting for disc size, age, refractive error, and IOP. The average (ⴞSD) number of abnormal test locations was similar in the 2 groups (P ⴝ .709), although CACG eyes were less likely to have paracentral points involved (47% vs 72%; P ⴝ .04). ● CONCLUSIONS: Patterns of glaucomatous damage seem to be different in CACG compared with POAG. This difference in patterns of damage may adversely affect detection of early disease or its progression in CACG. (Am J Ophthalmol 2011;152:74 – 80. © 2011 by Elsevier Inc. All rights reserved.)

Accepted for publication Jan 10, 2011. From the Glaucoma Division, Jules Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. Inquiries to Kouros Nouri-Mahdavi, 100 Stein Plaza, Los Angeles, CA 90095; e-mail: [email protected]

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NGLE-CLOSURE GLAUCOMA (ACG) IS BEING STUD-

ied more extensively as the significance of the disease is better recognized worldwide. Bilateral blindness from glaucoma is estimated to develop in 3.9 million persons with ACG by 2010, and it is expected to rise to 5.3 million persons by 2020.1 The focus of most recent ACG studies has been on imaging of the angle with newer devices and on better understanding of the pathophysiology of increased intraocular pressure (IOP). While these are important, there are also unanswered questions with regard to the natural course and mechanisms of the optic nerve and visual field damage in this type of glaucoma. The existing literature about patterns of glaucomatous damage and structure-function relationships in glaucoma is based mainly on eyes with primary open-angle glaucoma (POAG). However, ACG is typically a highpressure disease and factors other than the IOP seem less likely to be involved, at least during earlier stages of the disease. Therefore, structure-function relationships may not be the same in ACG. There is limited evidence in the literature showing that patterns of optic nerve damage in ACG may be different from POAG.2–5 A lower prevalence of peripapillary atrophy has been reported in eyes with ACG.2 Thomas and associates compared the Heidelberg Retina Tomograph (HRT) stereometric parameters and sensitivity/specificity of HRT algorithms in 2 groups of East Indian POAG and primary angle-closure patients.4 The main significant difference between the 2 groups was in the cup shape measure. However, Boland and associates found that the differences in HRT’s stereometric parameters such as the cup area, rim area, and cup-to-disc area ratio would disappear if a Bonferroni correction were applied.6 We undertook the current study to explore patterns of glaucomatous damage in chronic ACG (CACG) and to compare the findings to those in a group of POAG eyes matched for race and severity of visual field loss. We hypothesized that patterns of glaucomatous damage in CACG are different from those in eyes with POAG.

METHODS THE CLINICAL DATABASE AT THE GLAUCOMA DIVISION,

Jules Stein Eye Institute (Los Angeles, California, USA)

ELSEVIER INC. ALL

RIGHTS RESERVED.

0002-9394/$36.00 doi:10.1016/j.ajo.2011.01.008

TABLE 1. Characteristics of the Enrolled Eyes According to Diagnosis (Chronic AngleClosure Glaucoma vs Primary Open-Angle Glaucoma) CACG (n ⫽32)

POAG (n ⫽32)

P Value

Age (years, mean ⫾ SD) 68.3 ⫾ 11.6 Gender Male 15 (46.9%) Female 17 (53.1%) Ethnicity Hispanic 2 (6.2%) Non-Hispanic White 23 (71.9%) African American 3 (9.4%) Asian 4 (12.5%) Lens status Phakic 30 (93.8%) Pseudophakic 2 (6.2%) IOP at time of examination (mm Hg, mean ⫾ SD) 15.8 ⫾ 4.5 No. of medications at the time of examination (mean ⫾ SD) 1.4 ⫾ 1.4 LogMAR visual acuity (mean ⫾ SD) 0.13 ⫾ 0.16 Refractive error (diopters, mean ⫾ SD) 0.6 ⫾ 2.0 Visual field MD (dB, mean ⫾ SD) ⫺5.1 ⫾ 2.5 Visual field index (%, median and range) 92 (64–98) Visual field PSD (dB, mean ⫾ SD) 5.7 ⫾ 3.2

68.4 ⫾ 12.4

.819

14 (43.8%) 18 (56.2%)

.802

2 (6.2%)

N/A

Demographic Variable

23 (71.9%) 3 (9.4%) 4 (12.5%) 20 (62.5%) 12 (37.5%) 13.9 ⫾ 5.2 1.5 ⫾ 1.2 0.14 ⫾ 0.13 ⫺1.4 ⫾ 2.7 ⫺5.1 ⫾ 2.4 89 (59–96) 5.6 ⫾ 2.8

.002a .015b .575 .442 <.001b .931 .390 .809

CACG ⫽ chronic angle-closure glaucoma; IOP ⫽ intraocular pressure; MD ⫽ mean deviation; POAG ⫽ primary open-angle glaucoma; PSD ⫽ pattern standard deviation; SD ⫽ standard deviation. a 2 ␹ test. b Wilcoxon rank sum test. Bold font indicates significant P values (less than 0.05).

was retrospectively reviewed to find eyes with a diagnosis of CACG meeting specified criteria, with at least 1 available HRT image and a set of stereoscopic optic disc photographs taken within 1 year of visual fields demonstrating reproducible glaucomatous field loss. Chronic ACG was defined as: presence of visual field loss consistent with glaucoma along with presence of peripheral anterior synechiae or occludable angle (“s” configuration of the iris according to Spaeth’s classification), as determined by the attending ophthalmologist, along with a history of IOP ⬎21 mm Hg on no medications, or IOP ⬍21 mm Hg on medications or after glaucoma surgery, including peripheral laser iridotomy. Eligible patients were required to have at least 1 set of stereoscopic disc photographs and HRT image available (with global pixel standard deviation less than 50 ␮m) within 1 year of the eligible visual field exam. Only optic disc photographs with adequate quality for making a judgment with regard to pattern of disc damage were included. The eligible eyes were additionally required to have at least 2 reproducible 24-2 SITA-Standard visual fields meeting the following criteria: false-positive and falsenegative error rates ⬍25%; and confirmed abnormal pattern standard deviation (PSD) (p ⬍5%) or Glaucoma Hemifield Test “outside normal limits” and presence of a VOL. 152, NO. 1

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cluster of at least 3 test locations with p ⬍5% and at least 1 location with p ⬍1%. Fixation loss was not used as a criterion for selecting reliable fields. All the potentially eligible visual fields were reviewed by 1 of the authors (C.S.) and eyes with field loss attributable to lid or lens artifacts were excluded. Exclusion criteria were as follows: best-corrected visual acuity ⬍20/100, visual field mean deviation (MD) worse than ⫺15.0 dB, IOP less than 8 mm Hg on the day of imaging, presence of neurologic or retinal disease, history of acute or secondary angle-closure glaucoma, grossly anomalous disc shape such as disc hypoplasia or tilted disc, and refractive error ⬎8 diopters (D). In case both eyes of the same patient were eligible, the eye with the better visual field mean deviation was selected. Patients with POAG from the same database were chosen and matched for severity of visual field loss (mean deviation within 1 dB) and race. POAG eyes had open angles and evidence of visual field loss. In case more than 1 matching eye was found, the POAG eye with the closest mean deviation to the index case was chosen. Two experienced observers (K.N.M. and J.A.G.), masked to patient identity, date of exam, and other clinical information, reviewed the optic disc photographs. The observers graded clarity and stereopsis of the disc photographs on a 0-to-2 scale (0 ⫽ poor, 1 ⫽ fair, 2⫽ good) and checked for ANGLE-CLOSURE GLAUCOMA

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TABLE 2. Results of Qualitative Evaluation of Optic Disc Photographs by Reviewers CACG (Mean ⫾ SD)

POAG (Mean ⫾ SD)

P Value

1.84 ⫾ 0.32 1.75 ⫾ 0.36 0.89 ⫾ 0.34 0.66 ⫾ 0.16 8.0 ⫾ 2.1 6/32 (19%) 0.22 (0-1.25)

1.81 ⫾ 0.35 1.84 ⫾ 0.24 0.76 ⫾ 0.38 0.71 ⫾ 0.1 8.5 ⫾ 1.7 8/32 (25%) 0.24 (0.02-1.78)

.632d .402d .364d .401d .424d .545b .745d

a

Clarity score Stereoscopic quality scorea NFL visibility scorea Average cup-to-disc ratio Glaucoma certainty scorec Focal ischemic damage (%) B-PPA–to-disc-area ratio (median, range)

CACG ⫽ chronic angle-closure glaucoma; NFL ⫽ nerve fiber layer; POAG ⫽ primary open-angle glaucoma; SD ⫽ standard deviation. a 0-2 scale: 0 ⫽ poor, 1 ⫽ fair, 2⫽ good. b 2 ␹ test. c 0-10 scale: 0 ⫽ definitely normal, 10 ⫽ definitely glaucomatous. d Wilcoxon rank sum test. Bold font indicates significant P values (less than 0.05).

TABLE 3. Comparison of Stereometric Parameters From Heidelberg Retina Tomograph in Eyes With Chronic Angle-Closure and Primary Open-Angle Glaucoma

HRT Variable

CACG (Mean ⫾ SD) (n ⫽32)

POAG (Mean ⫾ SD) (n ⫽32)

P Value

Disc area (mm2) Cup area (mm2) Rim area (mm2) Cup volume (mm3) Rim volume (mm3) Rim-to-disc-area ratio Cup-to-disc-area ratio Linear cup-to-disc ratio Mean cup depth (mm) Max cup depth (mm) Cup shape measure Height variation contour Mean RNFL thickness (mm) RNFL cross-sectional area (mm2) FSM classification RB discriminant

2.12 ⫾ 0.41 0.92 ⫾ 0.47 1.20 ⫾ 0.44 0.25 ⫾ 0.22 0.27 ⫾ 0.15 0.57 ⫾ 0.19 0.43 ⫾ 0.19 0.62 ⫾ 0.24 0.27 ⫾ 0.14 0.65 ⫾ 0.24 ⫺0.11 ⫾ 0.07 0.39 ⫾ 0.16 0.17 ⫾ 0.09 0.90 ⫾ 0.50 ⫺0.55 ⫾ 2.34 0.11 ⫾ 0.95

2.18 ⫾ 0.49 1.16 ⫾ 0.46 1.02 ⫾ 0.31 0.36 ⫾ 0.26 0.22 ⫾ 0.09 0.48 ⫾ 0.13 0.52 ⫾ 0.13 0.70 ⫾ 0.10 0.34 ⫾ 0.11 0.76 ⫾ 0.19 ⫺0.08 ⫾ 0.07 0.36 ⫾ 0.11 0.19 ⫾ 0.06 0.98 ⫾ 0.35 ⫺1.44 ⫾ 1.54 0.05 ⫾ 0.80

.577 .045a .07 .026b .079 .03a .03a .354 .011b .044a .052 .768 .957 .489 .078 .802

CACG ⫽ chronic angle-closure glaucoma; FSM ⫽ FS Mikelberg; HRT ⫽ Heidelberg Retina Tomograph; POAG ⫽ primary open-angle glaucoma; SD ⫽ standard deviation; RB ⫽ R Bathija; RNFL ⫽ retinal nerve fiber layer. a t test. b Wilcoxon rank sum test. Bold font indicates significant P values (less than 0.05).

presence of focal rim loss (rim thinning ⱕ1 clock hour). Afterwards, the reviewers scored optic disc photographs for probability of glaucoma on a 10-level scale (glaucoma certainty score), with 10 being definitive glaucoma and 0 representing normal findings. The average of scores by the 2 reviewers was used for comparing the 2 groups. The optic disc photographs were then scanned and digitized as TIFF images with a resolution of 600 dots per inch with a digital 76

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slide scanner (Nikon LS-5000 ED film scanner, Nikon Corporation, Tokyo, Japan). One of the authors (K.N.M.) then sequentially delineated the area of beta-zone peripapillary atrophy (␤-PPA) and the disc using ImageJ software (National Institutes of Health, Bethesda Maryland, USA). The ratio of the ␤-PPA area to that of the disc area was calculated for each eye. Beta-zone peripapillary atrophy was defined as the crescent of chorioretinal atrophy with OF

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FIGURE. Distribution of global (Top row) and sectoral (Middle and Bottom rows) MRA results in chronic angle-closure (CACG) and primary open-angle glaucoma (POAG) eyes. P values are based on ␹2 tests. WNL ⴝ within normal limits; ONL ⴝ outside normal limits.

visible sclera and choroidal vessels immediately adjacent to the scleral ring. The HRT 3 software (version 1.5.10.0; Heidelberg Engineering, Heidelberg, Germany) was used to analyze images. The HRT contour lines were drawn by 1 of the authors (K.N.M.) after simultaneous review of the optic disc photographs. Of note, keratometry readings were not entered into the HRT to correct for image magnification. The HRT stereometric parameters were exported into a personal computer using the export function of the machine and disc size and other stereometric parameters were compared in the 2 groups. Heidelberg Retina Tomograph’s Moorfields Regression Analysis (MRA) and Glaucoma Probability Score (GPS) were also compared between the 2 groups. We compared the number of test locations with p ⬍5% for deviation from normal on pattern deviation plot in the 2 groups as a measure of extent of field loss. Also, the proportion of eyes with defects involving 1 of the 4 paracentral locations on the 24-2 strategy was determined. The number of test locations demonstrating VOL. 152, NO. 1

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p ⬍0.5% on the pattern deviation plot was also compared between the 2 groups as a measure of glaucomatous defect depth. Distribution of numerical data was evaluated with the Wilk-Shapiro test and normal quantile plots. Numerical data were compared with t test (normal data) and Wilcoxon rank sum test (for data with nongaussian distribution) and proportions were compared with ␹2 test. Multivariate linear regression models were built adjusting each of the HRT’s stereometric parameters individually for confounding factors (age, refractive error, IOP at the time of imaging, and disc area). In the multivariate models, each of the stereometric parameters was considered the dependent variable, with the diagnosis, age, refractive error, IOP at the time of imaging, and disc area entered into the model at once as independent variables. If the P value for diagnosis (reference: POAG group) was ⬍.05, that particular stereometric parameter was considered significantly different between the 2 groups. A similar multivariate model was used for adjusting the ␤-PPA–to-discarea ratio for diagnosis, age, and refractive error. ANGLE-CLOSURE GLAUCOMA

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imaging in multivariate linear regression models (P ⬍ .05 for all). Eyes with CACG were less likely to have evidence of global and inferotemporal sectoral rim loss (marked by a red cross denoting P ⬍ .001) on MRA compared with POAG eyes (P ⫽ .025 and P ⫽ .003, respectively; ␹2 test; Figure). No other significant differences were noted between the 2 groups with regard to other MRA sectors (P ⬎ .05), although the P value for the nasal sector almost reached statistical significance (P ⫽ .051). No difference in topographic distribution of damage was observed between the 2 groups when global and sectoral GPS results were compared (P ⬎ .05 for all comparisons). However, a large proportion of eyes (49-52 eyes out of 64 eyes, or 77%-81% of the eyes) displayed abnormal global or sectoral findings on GPS (marked by a red cross denoting P ⬍ .001).

RESULTS A TOTAL OF 64 EYES OF 64 PATIENTS (32 EYES IN EACH

group) were enrolled. Forty-two eyes had all the imaging and visual field examinations performed on the same day. Twenty-one eyes had the optic disc imaging done within a year of the eligible visual field. One patient was later found to have had the disc images performed 20 months after the eligible visual field but was included in the study. Table 1 compares the baseline characteristics of the 2 groups. The MD, visual field index, and PSD were similar in the 2 groups (average MD ⫽ ⫺5.1 dB for both groups). Eyes with CACG were more likely to be phakic at the time of the disc imaging (94% vs 63% in POAG eyes, P ⫽ .002, ␹2 test) and had higher IOP at the time of imaging (15.8 ⫾ 4.5 vs 13.9 ⫾ 5.2 mm Hg; P ⫽ .015, Wilcoxon rank sum test). Eyes with CACG were also more hyperopic than POAG eyes (⫹0.6 ⫾ 0.4 D vs ⫺1.4 ⫾ 0.5 D; P ⬍ .001, Wilcoxon rank sum test).

● VISUAL FIELD RESULTS: The average (⫾ SD) number of abnormal test locations (p ⬍5% on pattern deviation plot) was 17.8 (⫾5.6) in the CACG group and 17.3 (⫾5.2) in POAG eyes (P ⫽ .709; unpaired t test). The average number of test locations with the most significant level of loss (p ⬍0.5% on pattern deviation plot) was also similar in the 2 groups (8.7 ⫾ 6.2 vs 8.6 ⫾ 5.2; P ⫽ .924; unpaired t test). Eyes with CACG were less likely to have paracentral areas of the visual field involved (47% vs 72%; P ⫽ .04; ␹2 test) despite similar levels of visual field loss in the 2 groups.

● RESULTS OF REVIEW OF OPTIC DISC PHOTOGRAPHS:

Results of optic disc photograph review by clinicians are presented in Table 2. Overall, quality of the optic disc photographs was comparable between the 2 groups (P ⬎ .05 for all comparisons, Wilcoxon rank sum test). The glaucoma certainty scores were similar between the CACG and POAG eyes (mean ⫾ SD, 8.0 ⫾ 2.1 in CACG vs 8.5 ⫾ 1.7 for the POAG group; P ⫽ .424, Wilcoxon rank sum test). The prevalence of focal rim loss was not significantly lower in the CACG group (19% vs 25% in the POAG group; P ⫽ .545, ␹2 test). The ratio of ␤-PPA to disc area ranged from 0.02 to 1.78 in POAG eyes (median: 0.24) and from 0 to 1.25 in CACG eyes (median: 0.22; P ⫽ .559, Wilcoxon rank sum test). After adjusting for age and refractive error, no significant difference was observed between the 2 groups with respect to ␤-PPA–to-disc-area ratio (P ⫽ .745). Increasing age was positively related to the extent of the ␤-PPA–to-disc-area ratio (P ⫽ .034).

DISCUSSION THERE IS EVIDENCE IN THE LITERATURE THAT PATTERNS OF

glaucomatous disc or visual field damage may be different in CACG as compared to POAG. Zhao and associates compared the optic disc parameters of 20 eyes of 20 normal-tension glaucoma patients to those in 20 ACG patients.5 They found that the ACG eyes had shallower cups, lower maximal cup depths and cup volumes, larger rim areas, smaller vertical cup-to-disc ratios, and more negative (healthier) cup shape measures. Thomas and associates looked at the HRT stereometric parameters and sensitivity/specificity of HRT algorithms in 2 groups of East Indian POAG and CACG patients.4 The main significant difference in the subsets of patients with early glaucoma (average MD of ⫺3.9 and ⫺3.8 dB in POAG and PACG groups, respectively) was in the cup shape measure, which tended to be healthier in the early ACG patients (⫺0.14 vs ⫺0.9 for CACG and POAG groups; P ⫽ .016). Boland and associates found differences between the 2 groups as measured with HRT.6 The cup area, rim area, rim volume, cup-to-disc-area ratio, and cup shape measure were significantly different between ACG and POAG eyes. However, the authors argued that after a Bonferroni correction, the results were not statistically significant. Given the fact that

● IMAGING RESULTS: The HRT quality according to global pixel standard deviation was similar in the 2 groups, with a median (range) of 17.6 (12– 4123) and 17.5 (10 –38) ␮m in CACG and POAG groups, respectively. Disc area was similar in the 2 groups (P ⫽ .577, unpaired t test; Table 3). Eyes with CACG had smaller cup area, cup volume, cup-to-disc-area ratios, and mean and maximum cup depths and larger rim-to-disc area compared to POAG eyes (P ⬍ .05 for all; Table 3), whereas cup shape measure almost reached the cutoff point for significance (mean ⫾ SD: ⫺0.11 ⫾ 0.07 for CACG vs ⫺0.08 ⫾ 0.07 in POAG; unpaired t test, P ⫽ .052). All significant stereometric variables except for maximum cup depth (P ⫽ .055) remained significantly associated with group classification (CACG vs POAG) when the association was adjusted for disc area, age, refractive error, and IOP at the time of

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the stereometric HRT parameters are highly correlated, it is hard to justify using the Bonferroni correction to adjust P values in this setting. Another interesting finding from the study by Boland and associates was that ACG eyes had overall higher retinal nerve fiber layer thickness (as measured with optical coherence tomography) after adjusting for visual field mean deviation, HRT disc area, and eye length. We compared 2 groups of patients with CACG and POAG matched for severity of glaucoma (MD ⫾1 dB) and race in this study. Our hypothesis was that POAG eyes are more likely to have focal disc damage compared to eyes with CACG, which is typically considered to be a type of high-tension glaucoma. We also hypothesized that eyes with CACG may demonstrate less evidence of structural damage despite a similar level of functional loss based on preliminary findings in the literature. No significant difference in prevalence of focal rim loss was observed between the 2 groups on qualitative review of stereoscopic disc photographs. However, on quantitative analysis with HRT, eyes with CACG had smaller cup-to-disc-area ratios and shallower cups. They also had larger rim-to-disc ratios as well, since the disc size was not significantly different in the 2 groups. Heidelberg Retina Tomograph MRA results showed a higher prevalence of localized rim loss in the inferotemporal sector of the disc. The GPS findings were similar in the 2 groups of eyes. Most disc sectors were already out of normal limits (P ⬍ .001) on GPS; hence, it is hard to draw any conclusions from the GPS results. Zangwill and associates found GPS to be more sensitive than MRA and possibly have a higher false-positive rate compared to MRA.7 The fact that we did not find a higher prevalence of focal loss on qualitative review of disc photographs does not necessarily contradict the HRT findings. Qualitative review of disc photographs is a subjective process and therefore suffers from the shortcomings of any subjective test. Many investigators have reported an association between the ␤-PPA and presence of glaucomatous damage in open-angle glaucoma.8 –10 Presence of a zone of ␤-PPA has been shown to predict faster progression rates in eyes with glaucoma.11 However, Uchida and associates reported that in ACG eyes, both the prevalence and extent of peripapillary atrophy was significantly lower than a matched group of POAG eyes.2 Lee and associates found that peripapillary atrophy did not significantly enlarge after an acute episode of ACG despite an enlargement of the optic cup during a period of 4 months.12 We did not find a significant difference between the 2 groups with respect to the ␤-PPA–to-disc-area ratio although the CACG eyes did have a smaller ␤-PPA–to-disc-area ratio. Increasing myopia and age were associated with increasing ratio of ␤-PPA to disc area. There are scant data with regard to patterns of visual field loss in chronic ACG. Diffuse field depression has been reported to be more common after episodes of acute VOL. 152, NO. 1

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ACG.13 Gazzard and associates compared visual field findings in eyes with POAG and ACG enrolled in a prospective surgical treatment study.14 Overall, eyes with ACG had a lower PSD, which was interpreted as evidence for more diffuse field loss in ACG. The investigators also reported that after dividing the eyes according to glaucoma severity, POAG eyes were more likely to have evidence of localized defect in the superior hemifield. This is in agreement with our finding that inferotemporal rim loss was more common in POAG eyes. Rhee and associates reported similar findings in a small group of Korean patients with POAG and ACG.15 The extent and depth of visual field loss was similar between CACG and POAG eyes in our study. However, CACG eyes were less likely to have the paracentral locations of the visual field involved despite the same level of glaucoma severity, according to mean deviation and PSD. This finding, along with results of HRT MRA results, suggests that mechanisms of glaucoma damage might be different in the 2 diseases. A higher number of CACG patients were phakic (94% vs 63%), but the potential confounding effect of cataract on the visual field could not be measured given the retrospective nature of our study. However, the logMAR acuity and the visual field’s PSD were very similar in the 2 groups, which confirms that the media opacity influence was likely not significant. The ramifications of a different pattern of glaucomatous damage in CACG, if proven in a prospective study, would be significant. Clinicians are most familiar with patterns of glaucomatous disc damage in POAG and hence may underestimate the severity of damage in CACG eyes. Performance of optic disc imaging devices has also been most extensively evaluated in eyes with POAG. Parameters best discriminating glaucomatous from normal eyes may be different in CACG eyes, as reported by Thomas and associates.4 A set of parameters different from those applied to RB (R Bathija) or FSM (FS Mikelberg) discriminant functions of HRT may need to be selected to detect early glaucomatous damage in CACG eyes. If the above findings are confirmed, they will also have implications for detection of progression in CACG eyes. If changes in neuroretinal rim are less obvious given an identical amount of retinal ganglion cell loss, the current optic nerve head imaging algorithms may not be sensitive enough for the timely detection of glaucoma progression in CACG eyes and clinicians may need to rely more heavily on nerve fiber layer imaging and visual field findings for detection of progression. Also, clinicians are accustomed to seek the earliest evidence of localized glaucomatous damage in the inferotemporal area of the optic disc. While this area is the region where the earliest signs of glaucomatous damage becomes manifest in POAG, our findings suggest that this may not be the case in CACG eyes. The shortcomings of our study are as follows. The subjects were recruited from a tertiary-care academic glaucoma clinic and the number of enrolled eyes was fairly small. It is possible ANGLE-CLOSURE GLAUCOMA

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that our cohort of CACG eyes may not be representative of CACG eyes in the general population. Our cohort of patients was mostly composed of white subjects. It is possible that our results may not apply to CACG in other ethnicities. Ascertainment of CACG was based on retrospective review of examination notes recorded by glaucoma specialists. Some of the CACG eyes may have had an open-angle component contributing to glaucomatous damage. While this is a possibility, the ensuing confounding effect would have led to an underestimation of the difference between the 2 groups. We

did not have pretreatment IOPs for most patients and therefore could not group the POAG eyes according to this parameter. In summary, our findings suggest that patterns of optic nerve damage in eyes with chronic angle-closure glaucoma may be different in comparison to eyes with primary open-angle glaucoma. If the findings are confirmed in a larger prospective study, they may have significant implications with regard to early detection of the disease and its progression in eyes with chronic angle-closure glaucoma.

PUBLICATION OF THIS ARTICLE WAS SUPPORTED IN PART BY AN UNRESTRICTED GRANT FROM RESEARCH TO PREVENT Blindness, New York, New York. The authors report the following recent or current financial disclosures: Kouros Nouri-Mahdavi, Allergan Inc (consulting and lecture fees); Simon K. Law, Allergan Inc (lecture fees); Anne L. Coleman, Allergan Inc and Science Based Health (Advisory Board/consulting), Allergan Inc (grant support); Joseph Caprioli, Allergan Inc (lecture and consulting fees), and current research grant support from Pfizer, Allergan, and Alcon. Involved in design (K.N.M., C.S., E.B., S.L.K., A.L.C., J.C.), conduct of the study (C.S., K.N.M., J.A.G.); data collection (C.S., E.B., K.N.M.); management, analysis, and interpretation of the data (K.N.M., J.A.G., C.S.); and preparation, review, and approval of the manuscript (K.N.M., C.S., E.B., J.A.G., S.K.L., A.L.C., J.C.). The study was approved by the Institutional Review Board at UCLA and followed the tenets of the Declaration of Helsinki.

8. Jonas JB, Fernandez MC, Naumann GO. Glaucomatous parapapillary atrophy. Occurrence and correlations. Arch Ophthalmol 1992;110(2):214 –222. 9. Tezel G, Kolker AE, Wax MB, Kass MA, Gordon M, Siegmund KD. Parapapillary chorioretinal atrophy in patients with ocular hypertension. II. An evaluation of progressive changes. Arch Ophthalmol 1997;115(12):1509 –1514. 10. Park KH, Park SJ, Lee YJ, Kim JY, Caprioli J. Ability of peripapillary atrophy parameters to differentiate normaltension glaucoma from glaucomalike disk. J Glaucoma 2001; 10(2):95–101. 11. Teng CC, De Moraes CG, Prata TS, Tello C, Ritch R, Liebmann JM. Beta-Zone parapapillary atrophy and the velocity of glaucoma progression. Ophthalmology 2010;117(5):909–915. 12. Lee KY, Rensch F, Aung T, et al. Peripapillary atrophy after acute primary angle closure. Br J Ophthalmol 2007;91(8): 1059 –1061. 13. Douglas GR, Drance SM, Schulzer M. The visual field and nerve head in angle-closure glaucoma. A comparison of the effects of acute and chronic angle closure. Arch Ophthalmol 1975;93(6):409 – 411. 14. Gazzard G, Foster PJ, Viswanathan AC, et al. The severity and spatial distribution of visual field defects in primary glaucoma: a comparison of primary open-angle glaucoma and primary angle-closure glaucoma. Arch Ophthalmol 2002; 120(12):1636 –1643. 15. Rhee K, Kim YY, Nam DH, Jung HR. Comparison of visual field defects between primary open-angle glaucoma and chronic primary angle-closure glaucoma in the early or moderate stage of the disease. Korean J Ophthalmol 2001;15(1):27–31.

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Biosketch Kouros Nouri-Mahdavi, MD MSc, is Assistant Professor of Ophthalmology at the Glaucoma Division, Jules Stein Eye Institute, University of California Los Angeles. His research interests include role of functional and electrophysiological tests for detection of glaucoma or its progression, optic disc and retinal nerve fiber layer imaging, and study of treatment outcomes in glaucoma.

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Biosketch Chutima Supawavej, MD, graduated from Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Thailand. She completed her residency in Ophthalmology and a clinical fellowship in glaucoma at Rajavithi Hospital, Thailand. She was an International Fellow and Adjunct Instructor in the Glaucoma Division at the Jules Stein Eye Institute, University of California Los Angeles in 2009 –10. Dr. Supawavej is currently a glaucoma specialist at BNH and Samitivej Hospitals, Bangkok, Thailand. Her special interests include angle-closure glaucoma and management of difficult glaucomas.

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