To compare patterns of damage in chronic angle-closure glaucoma (CACG) to a control group of patients with primary open-angle glaucoma (POAG).
Retrospective cross-sectional study.
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 μm) and stereoscopic disc photographs within 1 year of a visual field showing reproducible glaucomatous field loss (mean deviation ≥−15.0 dB) were enrolled. Control eyes with POAG meeting similar criteria and matched for severity of field loss (±1 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.
The average mean deviation was −5.1 dB in both groups. Patients with CACG were more hyperopic (0.6 ± 0.4 vs −1.4 ± 0.5 D; P < .001) and had higher IOP at the time of imaging (15.8 ± 0.8 vs 13.9 ± 0.9 mm Hg; P = .015). Focal disc damage was not less frequent in PACG eyes (19% vs 24%; P = .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 (±SD) number of abnormal test locations was similar in the 2 groups ( P = .709), although CACG eyes were less likely to have paracentral points involved (47% vs 72%; P = .04).
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.
Angle-closure glaucoma (ACG) is being studied 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. 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 high-pressure 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. A lower prevalence of peripapillary atrophy has been reported in eyes with ACG. 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. 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. 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.
The clinical database at the Glaucoma Division, Jules Stein Eye Institute (Los Angeles, California, USA) 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 μm) 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 false-negative error rates <25%; and confirmed abnormal pattern standard deviation (PSD) (p <5%) or Glaucoma Hemifield Test “outside normal limits” and presence of a 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 presence of focal rim loss (rim thinning ≤1 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 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 (β-PPA) and the disc using ImageJ software (National Institutes of Health, Bethesda Maryland, USA). The ratio of the β-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 visible sclera and choroidal vessels immediately adjacent to the scleral ring.
The HRT 3 software (version 22.214.171.124; 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 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 χ 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 β-PPA–to-disc-area ratio for diagnosis, age, and refractive error.
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, χ 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).
|Demographic Variable||CACG (n =32)||POAG (n =32)||P Value|
|Age (years, mean ± SD)||68.3 ± 11.6||68.4 ± 12.4||.819|
|Male||15 (46.9%)||14 (43.8%)||.802|
|Female||17 (53.1%)||18 (56.2%)|
|Hispanic||2 (6.2%)||2 (6.2%)||N/A|
|White||23 (71.9%)||23 (71.9%)|
|African American||3 (9.4%)||3 (9.4%)|
|Asian||4 (12.5%)||4 (12.5%)|
|Phakic||30 (93.8%)||20 (62.5%)||.002 a|
|Pseudophakic||2 (6.2%)||12 (37.5%)|
|IOP at time of examination (mm Hg, mean ± SD)||15.8 ± 4.5||13.9 ± 5.2||.015 b|
|No. of medications at the time of examination (mean ± SD)||1.4 ± 1.4||1.5 ± 1.2||.575|
|LogMAR visual acuity (mean ± SD)||0.13 ± 0.16||0.14 ± 0.13||.442|
|Refractive error (diopters, mean ± SD)||0.6 ± 2.0||−1.4 ± 2.7||<.001 b|
|Visual field MD (dB, mean ± SD)||−5.1 ± 2.5||−5.1 ± 2.4||.931|
|Visual field index (%, median and range)||92 (64–98)||89 (59–96)||.390|
|Visual field PSD (dB, mean ± SD)||5.7 ± 3.2||5.6 ± 2.8||.809|
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, χ 2 test). The ratio of β-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 β-PPA–to-disc-area ratio ( P = .745). Increasing age was positively related to the extent of the β-PPA–to-disc-area ratio ( P = .034).
|CACG (Mean ± SD)||POAG (Mean ± SD)||P Value|
|Clarity score a||1.84 ± 0.32||1.81 ± 0.35||.632 d|
|Stereoscopic quality score a||1.75 ± 0.36||1.84 ± 0.24||.402 d|
|NFL visibility score a||0.89 ± 0.34||0.76 ± 0.38||.364 d|
|Average cup-to-disc ratio||0.66 ± 0.16||0.71 ± 0.1||.401 d|
|Glaucoma certainty score c||8.0 ± 2.1||8.5 ± 1.7||.424 d|
|Focal ischemic damage (%)||6/32 (19%)||8/32 (25%)||.545 b|
|B-PPA–to-disc-area ratio (median, range)||0.22 (0-1.25)||0.24 (0.02-1.78)||.745 d|
a 0-2 scale: 0 = poor, 1 = fair, 2= good.
c 0-10 scale: 0 = definitely normal, 10 = definitely glaucomatous.
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) μm 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 imaging in multivariate linear regression models ( P < .05 for all).