Elena Bitrian

A Method to Measure and Predict Rates of Regional Visual Field Decay in Glaucoma

PURPOSE This study was conducted to measure the rate of visual field (VF) decay in glaucoma, to separate faster and slower components of decay, and to predict the rate of VF decay. METHODS Patients who had primary glaucoma and 6 or more years of follow-up were included. Thresholds at each VF location were regressed with linear, quadratic, and exponential models. The best model was used to parse the VF into slower and faster rate components. Two independent cohorts (glaucoma [n = 87] and cataract [n = 38]) were used to determine the techniques ability to distinguish areas of glaucomatous VF changes from those caused by cataract. VF forecasts, derived from the first half of follow-up, were compared with actual VF thresholds at the end of follow-up. RESULTS The mean (±SD) years of follow-up and number of VFs for the main cohort (389 eyes of 309 patients) were 8.2 (±1.1) years and 15.7 (±3.0), respectively. The proportions of best fits were linear 2%, quadratic 1%, and exponential 97%. Proportions of eyes with exponential rates of decay ≥10% for the entire visual field (VF), faster components, and slower components were 20%, 56%, and 4%, respectively. The difference in decay rates between the faster and slower components was greater in the independent glaucoma cohort (19% ± 10%) than in the cataract cohort (5% ± 5%; P < 0.001). Test location forecasts significantly correlated with measured values (r(2) = 0.67; P < 0.001). CONCLUSIONS This method isolates faster and slower components of VF decay in glaucoma, can identify patients who are fast progressors, and can predict patterns of future VF loss with appropriate confidence intervals. (ClinicalTrials.gov number, NCT00000148.).

Measurement of optic disc size and rim area with spectral-domain OCT and scanning laser ophthalmoscopy.

PURPOSE To compare optic disc and neuroretinal rim area measurements from spectral-domain optical coherence tomography (SD-OCT) to those from confocal scanning laser ophthalmoscopy. METHODS Seventy-one eyes from 43 normal subjects or suspected/definite glaucoma patients were prospectively enrolled. All subjects had biometry with the IOLMaster and disc/retinal nerve fiber layer imaging with Cirrus SD-OCT (Optic Disc Cube 200×200) and Heidelberg Retina Tomograph (HRT). Uncorrected disc and rim areas and measurements corrected for eye magnification with Bennetts formula (AL-corrected measurements), along with 30° sectoral rim areas, vertical cup-to-disc ratio (VCDR), and cup volume, were compared between the two devices. RESULTS The median (range) axial length (AL) was 24.2 mm (22.4-27.7 mm). Mean keratometry-corrected HRT disc area measurements were larger than AL-corrected HRT and SD-OCT measurements (P < 0.001 for both) and the difference was a function of keratometry measurements (K-readings). The AL-corrected HRT disc area and uncorrected/corrected Cirrus disc areas were not significantly different (P > 0.481). HRT rim area was larger than Cirrus measurements (P < 0.001) and the difference decreased with decreasing rim area. HRT VCDR and cup volume were significantly smaller than Cirrus measurements (P < 0.001). The correlations for sectoral rim areas between the two devices were moderate at best (intraclass correlation coefficients = 0.12-0.65). CONCLUSIONS HRT overestimated optic disc area as compared to SD-OCT. A portion of the difference in HRT and SD-OCT disc measurements is due to HRTs magnification correction algorithm. Rim area measurements from HRT were larger than from SD-OCT, likely a result of different definitions for the reference plane and differences in disc area measurements. Disc parameters from the two devices are not interchangeable.

Pars Plana Anterior Vitrectomy, Hyaloido-Zonulectomy, and Iridectomy for Aqueous Humor Misdirection

PURPOSE To report a surgical technique for aqueous misdirection refractory to medical treatment consisting of combined pars plana vitrectomy, hyaloido-zonulectomy, and peripheral iridectomy. DESIGN Noncomparative case series. METHODS The charts of 5 pseudophakic patients who sought treatment for aqueous humor misdirection refractory to medical treatment from May 2008 trough February 2009 were reviewed. All 5 patients underwent anterior vitrectomy, hyaloido-zonulectomy, and peripheral iridectomy with an anterior vitrector through a pars plana incision. Main outcome measures were preoperative and postoperative visual acuity, intraocular pressure, medications, slit-lamp examination results, and fundus findings. RESULTS Five female patients (age range, 23 to 89 years) had increased intraocular pressure and shallowing of the anterior chamber after cataract extraction or trabeculectomy, and none responded to conventional medical therapy. After surgery, prompt resolution of the aqueous misdirection was achieved in all cases. The follow-up was 7.6 months (range, 1 to 13 months). CONCLUSIONS Aqueous misdirection refractory to medical treatment can be treated successfully with surgery consisting of partial pars plana vitrectomy, hyaloido-zonulectomy, and peripheral iridectomy.

Pointwise rates of visual field progression cluster according to retinal nerve fiber layer bundles.

PURPOSE To explore whether pointwise rates of visual field progression group together in patterns consistent with retinal nerve fiber layer (RNFL) bundles. METHODS Three hundred eighty-nine eyes of 309 patients from the Advanced Glaucoma Intervention Study with ≥6 years of follow-up and ≥12 reliable visual field exams were selected. Linear and exponential regression models were used to estimate pointwise rates of change over time. Clustering of pointwise rates of progression was investigated with hierarchical cluster analysis using Pearsons correlation coefficients as distance measure and an average linkage scheme for building the hierarchy with cutoff value of r > 0.7. RESULTS The average mean deviation (±SD) was -10.9 (±5.4). The average (±SD) follow-up time and number of visual field exams were 8.1 (±1.1) years and 15.7 (±3.0), respectively. Pointwise rates of progression across the visual field grouped into clusters consistent with anatomic patterns of RNFL bundles with both linear (10 clusters) and exponential (six clusters) regression models. One hundred forty-four (37%) eyes progressed according to the two-omitting pointwise linear regression model. CONCLUSIONS ointwise rates of change in glaucoma patients cluster into regions consistent with RNFL bundle patterns. This finding validates the clinical significance of such pointwise rates. The correlations among pointwise rates of change can be used for spatial filtering purposes, facilitating detection or prediction of glaucoma progression.

Comparison of Clinical Characteristics Between Korean and Western Normal-Tension Glaucoma Patients

PURPOSE To detect potential differences in the phenotypes between Western normal-tension glaucoma (NTG) and Korean NTG. DESIGN A retrospective, cross-sectional study. METHODS One hundred eighty-four NTG eyes of 71 patients of the Jules Stein Eye Institute, University of California, Los Angeles, and 113 patients of the Seoul National University Hospital, Seoul, Korea, were studied after reviewing medical charts retrospectively. All eligible patients from both institutions who were evaluated between July 2007 and June 2008 were included. The groups were matched for stage of glaucoma severity based on the visual field mean deviation value. All patients underwent a complete ophthalmic examination, Humphrey perimetry, Heidelberg Retina Tomography, Stratus optical coherence tomography, and pachymetry. Structural and functional parameters between the 2 groups were compared. RESULTS There were no statistically significant differences in the baseline intraocular pressure, disc area, frequency of disc hemorrhage, or peripapillary atrophy (P > .05). Cup-shape measure (by Heidelberg Retina Tomography), average RNFL thickness (by Stratus optical coherence tomography), and central corneal thickness were significantly different (P < .002). The eyes of Korean NTG patients showed higher values for cup-shape measure, higher average RNFL thicknesses, and thinner central corneal thicknesses than Western NTG patients. The difference was significant (P < .001) while controlling for age, sex, disc area, mean deviation, pattern standard deviation, and spherical equivalent with multivariate analysis. CONCLUSIONS Korean NTG patients showed steeper cup shapes, thicker RNFL thickness, and thinner central corneal thickness compared with Western NTG patients with similar amounts of visual field loss. This result may help clinicians understand the clinical characteristics of NTG patients and points to the heterogeneous character of the glaucomas.

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

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 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. RESULTS 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). 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.

Bleb Revision for Resolution of Hypotony Maculopathy Following Primary Trabeculectomy

PURPOSE To describe a surgical method of bleb revision for hypotony maculopathy, to evaluate its long-term efficacy, and to define the relationship between the duration of hypotony maculopathy and visual acuity (VA) outcomes. DESIGN Noncomparative retrospective case series. METHODS Medical records of 33 patients with hypotony maculopathy who underwent primary bleb revision between June 1999 and September 2012 by a single surgeon at an academic medical center were reviewed. Hypotony maculopathy was characterized by the presence of a decrease in VA, retinal striae, and macular edema in the setting of decreased intraocular pressure (IOP) after glaucoma filtering surgery. The main outcome measure was final logMAR VA after bleb revision at 6 and 12 months. RESULTS Thirty-three eyes of 33 patients were followed for 4.68 ± 3.56 years (range 0.55-12.69 years). Mean duration of hypotony maculopathy was 4.98 ± 8.93 months. LogMAR VA improved from 0.78 ± 0.40 at baseline to 0.34 ± 0.34 (P < .001) 6 months after bleb revision and to 0.45 ± 0.55 (P < .001) 12 months after bleb revision. Spearman rank coefficient (rs) correlating duration of hypotony and BCVA at both 6 and 12 months was significant (P = .015 and rs = 0.426, P = .028 and rs = 0.416, respectively). Mean IOP increased from 3.51 ± 2.27 mm Hg to 12.06 ± 4.06 mm Hg (P < .001) at 12 months. Fifty-two percent were on no antiglaucoma medications at last follow-up. Five eyes (15%) required a second bleb revision to correct persistent hypotony maculopathy. CONCLUSION Surgical repair for hypotony maculopathy provided a significant improvement in VA at 6 and 12 months. Surgical bleb revision is associated with good long-term control of IOP and improved VA in eyes with hypotony maculopathy after previous glaucoma filtering surgery.

Author response: on alternative methods for measuring visual field decay: Tobit linear regression.

The authors thank Russell and Crabb for their thoughtful comments about our paper published in the June issue of IOVS. We are grateful for this opportunity to respond to their suggestions. Crabb and coworkers (McNaught et al.) have previously published on pointwise models to fit longitudinal visual field loss in glaucoma. They concluded that linear regression is the best fit compared with other models, including exponential. The exponential model that Crabb et al. used in their study is fundamentally different from the one we reported. The exponential model that they reported took the form of y a be (linear exponential), whereas our model takes the form of y e a bx (nonlinear exponential), where y is visual sensitivity, x is time, and b the rate-of-change coefficient. In the former case, the exponential fit has a convex upward shape, whereas the latter has a concave upward shape, as in classic exponential decay. The nonlinear exponential model seems a more appropriate way to model these data and may be the reason it overwhelmingly fits the data better than the simple linear model in our study. Additional data supporting this conclusion are given below. Russell and Crabb suggest that the nonlinear exponential model works well in advanced visual field loss (as in the Advanced Glaucoma Intervention Study, AGIS), because of the “floor” (zero decibel) effect found in advanced visual field loss. We performed a similar analysis in a separate set of visual field series from patients at UCLA (Caprioli J, et al. IOVS 2011;52: ARVO E-Abstract 4410). Compared with AGIS, these were patients with much less severe visual field abnormalities with an initial average mean defect of 5 dB compared with 11 dB in AGIS). We also found, based on the Akaike information criteria (AIC) for these 22,086 data series, that the exponential model provided better data fits than the linear model 95% of the time. Russell and Crabb made a reasonable suggestion to use a Tobit linear regression model. This is based on the modeling of a theoretical data series presented in their letter that describes a very specific set of conditions: a linear drop of sensitivities to the “floor” of threshold measurements, which subsequently and consistently remain at 0. In this example, the Tobit regression, which censors the “floor” effect, is best. Of course, this pattern does not predominate in real life, even in patients with advanced field loss. When we reanalyzed the AGIS visual field data and performed Tobit fits for all 21,006 data series, we found that, based on the AIC, the exponential model performed better than the Tobit model in 82% of the data series. Hence, the Tobit model shows an improvement over the simple linear fits, but the exponential model still provided the best fit for the preponderance of the data. We again performed the Tobit linear regression in the UCLA data set of less advanced glaucoma, and, based on the AIC, exponential fits were better 92% of the time. An issue with the Tobit fits that is that since, after a certain time point, it may censor sensitivities that are above 0, it cannot be used to make meaningful predictions in visual fields with moderately advanced, but not absolute, loss. We further analyzed the fits for the combined AGIS and UCLA visual field data series (n 798 eyes with mean follow-up, 9.4 years; mean number of visual field examinations per eye, 15.2; and total number of data series, 43,092) and found the following proportions of best fits based on the AIC: nonlinear exponential, 88.1%; linear, 0.2%; linear exponential, 3.1%; and Tobit, 8.5%. One can see that the nonlinear exponential model clearly predominated. When simple linear is compared only to the linear exponential, the results are: linear 62.4% versus linear exponential 37.6%, which explains the published findings of McNaught et al. The exponential decay model, where the rate is proportional to the volume of visual function that remains, seems to mimic the pathophysiology of glaucoma. Patients with chronic glaucomas under treatment rarely go completely blind; rather, they approach perimetric blindness asymptotically, with some visual sensitivity usually preserved. Hence, the exponential decay model seems generally more appropriate than the linear model, which plunges through the “floor,” or the Tobit, which plunges to the “floor.” Finally, Russell and Crabb suggest that the exponential decay shape may also be a result of multiple treatments. However, the exponential model also predominated in patients under treatment in the UCLA group, wherein, as opposed to AGIS, only a minority had had surgery. Certianly, Russell and Crabb would also agree that we wish to model glaucoma patients under treatment. We propose that a possible area for future work is to use a combination of models at different locations throughout the visual field, depending on their goodness of fit. The authors thank Russell and Crabb for their insightful suggestions and the Editor for the opportunity to respond. Joseph Caprioli, Dennis Mock Elena Bitrian Abdelmonem Afifi Fei Yu Kouros Nouri-Mahdavi Anne Coleman