Pamela A. Sample

Detection of early glaucomatous structural damage with confocal scanning laser tomography.

PURPOSE The authors determine which optic disc topographic parameters obtained by the Heidelberg Retina Tomograph (HRT, Heidelberg Engineering, Heidelberg, Germany) are most useful in detecting individuals with early glaucomatous visual field loss. METHODS Ninety-nine eyes of 49 healthy individuals and 50 age-matched individuals with early glaucomatous visual field loss were included. Three images were obtained and the mean topography image was created and used in the analyses. The HRT discriminant analysis function (software version 2.01) was applied and compared to the Fisher linear discriminant function developed in this population. Analysis was repeated after stratifying by disc area (< 2 mm2 or 2-3 mm2). RESULTS There were statistically significant differences between the healthy and glaucomatous groups for all optic disc topographic parameters (p < 0.05) measured. These differences remained after the analysis was repeated controlling for disc size, except for height variation contour. Applying the HRT discriminant function to this study population resulted in sensitivity and specificity of 62% and 94%, respectively. The sensitivity was 83% while specificity remained high (91%) for larger disc sizes. Using this data, additional discriminant functions that differentiated similarly between the two groups were found. The best formula used cup-shape measure (third moment), rim area, height variation contour, and retinal nerve fiber layer thickness and had a sensitivity and specificity of 78% and 88%, respectively. CONCLUSIONS Several different discriminant analysis formulas are capable of detecting early glaucomatous visual field loss in a comparable manner. The characteristics of the study population are likely to influence the discriminating power of these various formulas.

Corneal thickness as a risk factor for visual field loss in patients with preperimetric glaucomatous optic neuropathy.

PURPOSE To determine whether central corneal thickness (CCT) is a risk factor for visual field loss development among patients diagnosed with preperimetric glaucomatous optic neuropathy (GON). DESIGN Observational cohort study. METHODS The study included 98 eyes of 98 patients with GON, with a mean follow-up time of 4.3 +/- 2.7 years. Diagnosis of GON was based on masked assessment of optic disk stereophotographs. All patients had normal standard automated perimetry visual fields at baseline. Criteria for visual field abnormality were derived from a prior study. Several clinical factors (CCT, intraocular pressure, vertical cup-to-disk ratio, refraction, age, gender, family history of glaucoma, high blood pressure, cardiovascular disease, and migraine) were investigated to ascertain whether there is an association with development of repeatable visual field loss. Cox proportional hazards models were used to obtain hazard ratios (HR) and identify factors that predicted which individuals developed glaucomatous visual field loss during the follow-up period. RESULTS Thirty-four patients (35%) developed repeatable visual field abnormality during follow-up. In multivariate analysis, risk factors that predicted the development of visual field loss were a thinner CCT (adjusted HR = 1.62/40 microm thinner; P =.023; 95% confidence interval [CI]: 1.07-2.45), higher baseline intraocular pressure (adjusted HR = 1.07/mm Hg; P =.022; 95% CI: 1.01-1.14), and larger baseline vertical cup-to-disk ratio (adjusted HR = 1.63/0.1 larger; P =.009; 95% CI: 1.13-2.35). The mean +/- standard deviation CCT of GON patients who developed visual field loss was 543 +/- 36 microm compared with 565 +/- 35 microm of those who did not develop visual field abnormalities (P =.005, Student t test). CONCLUSIONS Central corneal thickness is a risk factor for development of visual field loss among patients diagnosed with preperimetric GON. It is important to consider CCT when establishing target intraocular pressure of patients with GON.

Association Between Quantitative Nerve Fiber Layer Measurement and Visual Field Loss in Glaucoma

PURPOSE To evaluate the association between quantitative nerve fiber layer measurements and visual field loss in patients with primary open-angle glaucoma. METHODS Quantitative retinal nerve fiber layer measurements were obtained in 53 patients with primary open-angle glaucoma by using confocal scanning laser ophthalmoscopy (cross-section area) and confocal scanning laser polarimetry (retardation ratio). For each eye, three images were obtained with each instrument. An image that was the mean of those three was created and used in all analyses. We investigated the association between global, regional, and hemifield differences in retinal nerve fiber layer measurements and visual field loss with linear regression techniques. RESULTS The retardation ratio decreased with increasing mean visual field loss, measured both globally and regionally; R2 (the amount of variation explained by the model) ranged from 8% to 21%. Retinal nerve fiber layer cross-section area was not significantly associated with global measures of visual field loss. The inferior visual field mean deviation increased with decreasing superior retinal nerve fiber layer cross-section area (R2 = 8.2%, P = .04); superior visual field mean deviation was not associated with inferior retinal nerve fiber layer cross-section area (R2 = 2.6%, P = .25). Hemifield differences in visual field mean deviation increased with increasing hemifield differences in retinal nerve fiber layer cross-section area (R2 = 20.0%, P < .001), but not with retardation ratio (R2 = 0.9%, P = .48). CONCLUSIONS Quantitative measures of the retinal nerve fiber layer using both confocal scanning laser ophthalmoscopy and confocal scanning laser polarimetry were correlated with visual field loss in glaucoma patients.

Short-wavelength Color Visual Fields in Glaucoma Suspects at Risk

Glaucoma suspect eyes were seen during a five-year study on color visual fields that used a 440-nm test on a bright-yellow background (96 normal eyes, 55 suspect eyes, and 110 eyes that developed glaucoma). The predictive ability of the test was assessed in 25 eyes followed up for more than one year, five of which developed glaucoma. These five eyes and those at high risk showed higher mean defect (P < .0001) and number of defective points (P < .0001) than the other suspect groups, which were not significantly different from normal eyes. The mean defects (+/- standard deviations) and average number of defective points were 1.4 +/- 2.3 dB with 8.9 points (low-risk eyes), 1.1 +/- 1.2 dB with 8.0 points (medium-risk eyes), 6.7 +/- 2.8 dB with 27.7 points (high-risk eyes), and 9.3 +/- 1.8 dB with 39.4 points (eyes that developed glaucoma). Normal eyes had an average of 3.4 defective points. These results were similar when all 55 suspect eyes were analyzed. Color visual fields identify early functional loss in eyes at greatest risk for primary open-angle glaucoma.

Agreement between Spectral-Domain and Time-Domain OCT for measuring RNFL thickness.

Background/aims: To evaluate spectral-domain (SD) optical coherence tomography (OCT) reproducibility and assess the agreement between SD-OCT and Time-Domain (TD) OCT retinal nerve fibre layer (RNFL) measurements. Methods: Three Cirrus-SD-OCT scans and one Stratus-TD-OCT scan were obtained from Diagnostic Innovations in Glaucoma Study (DIGS) healthy participants and glaucoma patients on the same day. Repeatability was evaluated using Sw (within-subject standard deviation), CV (coefficient of variation) and ICC (intraclass correlation coefficient). Agreement was assessed using correlation and Bland–Altman plots. Results: 16 healthy participants (32 eyes) and 39 patients (78 eyes) were included. SD-OCT reproducibility was excellent in both groups. The CV and ICC for Average RNFL thickness were 1.5% and 0.96, respectively, in healthy eyes and 1.6% and 0.98, respectively, in patient eyes. Correlations between RNFL parameters were strong, particularly for average RNFL thickness (R2 = 0.92 in patient eyes). Bland–Altman plots showed good agreement between instruments, with better agreement for average RNFL thickness than for sectoral RNFL parameters (for example, at 90 µm average RNFL thickness, 95% limits of agreement were −13.1 to 0.9 for healthy eyes and −16.2 to −0.3 µm for patient eyes). Conclusions: SD-OCT measurements were highly repeatable in healthy and patient eyes. Although the agreement between instruments was good, TD-OCT provided thicker RNFL measurements than SD-OCT. Measurements with these instruments should not be considered interchangeable.

Primary Open-Angle Glaucoma in Blacks: A Review

Glaucoma is one of the leading causes of blindness worldwide. Primary open-angle glaucoma (POAG) is the most prevalent form of glaucoma and has a particularly devastating impact in blacks. In the black American population, POAG prevalence is estimated to be six times as high in certain age groups compared to whites. POAG is more likely to result in irreversible blindness, appears approximately 10 years earlier and progresses more rapidly in blacks than in whites. Racial differences in optic disk parameters have been reported and show that blacks have larger optic disks than whites. This finding is robust and may account for the reported differences in other optic disk parameters. The existence of racial differences in intraocular pressure remains to be demonstrated, as conflicting findings are reported in the literature. Intraocular pressure may actually be underestimated in blacks, perhaps because they have thinner corneas. The prevalence of diabetes and hypertension is higher in blacks than in whites, and although no causal relationship has been established between POAG and each of these systemic diseases, some reports suggest that they often occur together, perhaps through an indirect relationship with intraocular pressure. Compounding the problem, there is evidence that blacks are less responsive to both drug and surgical treatment for POAG. Finally, they often have reduced accessibility to treatment and are less aware of the risks of having POAG. This article provides a comprehensive review of the current knowledge pertaining to POAG in blacks.

Comparison of Different Spectral Domain Optical Coherence Tomography Scanning Areas for Glaucoma Diagnosis

PURPOSE To evaluate retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular thickness measurements for glaucoma detection using the RTVue spectral domain optical coherence tomograph. DESIGN Diagnostic, case-control study. PARTICIPANTS One hundred forty eyes of 106 glaucoma patients and 74 eyes of 40 healthy subjects from the Diagnostic Innovations in Glaucoma Study (DIGS). METHODS All patients underwent ocular imaging with the commercially available RTVue. Optic nerve head, RNFL thickness, and macular thickness scans were obtained during the same visit. Receiver operating characteristic (ROC) curves and sensitivities at fixed specificities (80% and 95%) were calculated for each parameter. MAIN OUTCOME MEASURES Areas under the ROC curves (AUC) and sensitivities at fixed specificities of 80% and 95%. RESULTS The AUC for the RNFL parameter with best performance, inferior quadrant thickness, was significantly higher than that of the best-performing ONH parameter, inferior rim area (0.884 vs 0.812, respectively; P = 0.04). There was no difference between ROC curve areas of the best RNFL thickness parameters and the best inner macular thickness measurement, ganglion cell complex root mean square (ROC curve area = 0.870). CONCLUSIONS The RTVue RNFL and inner retinal macular thickness measurements had good ability to detect eyes with glaucomatous visual field loss and performed significantly better than ONH parameters.

Detection of glaucoma progression with stratus OCT retinal nerve fiber layer, optic nerve head, and macular thickness measurements.

PURPOSE To evaluate and compare the ability of optical coherence tomography (OCT) retinal nerve fiber layer (RNFL), optic nerve head, and macular thickness parameters to detect progressive structural damage in glaucoma. METHODS This observational cohort study included 253 eyes of 253 patients. Images were obtained annually with the Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA) along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. The median follow-up time was 4.01 years. Progression was determined by the Guided Progression Analysis software for SAP (Carl Zeiss Meditec, Inc.) and by masked assessment of optic disc stereophotographs performed by expert graders. Random coefficient models and receiver operating characteristic (ROC) curves were used to evaluate the relationship between change in Stratus OCT parameters over time and progression as determined by SAP and/or stereophotographs. RESULTS From the 253 eyes, 31 (13%) showed progression over time by stereophotographs and/or SAP. Mean rates of change in average RNFL thickness were significantly higher for progressors compared with nonprogressors (-0.72 mum/y vs. 0.14 mum/y; P = 0.004), with sensitivity of 77% for specificity of 80%. RNFL parameters performed significantly better than ONH and macular thickness measurements in discriminating progressors from nonprogressors. The parameters with the largest ROC curve areas for each scanning area were inferior RNFL thickness (0.84), cup area (0.66), and inferior inner macula thickness (0.64). CONCLUSIONS Stratus OCT RNFL parameters discriminated between eyes progressing by visual fields or optic disc photographs and eyes that remained stable by these methods and performed significantly better than ONH and macular thickness parameters in detecting change over time.

The African descent and glaucoma evaluation study (ADAGES): Design and baseline data

OBJECTIVE To identify factors accounting for differences in glaucoma onset and rate of progression between individuals of African descent and European descent. DESIGN A prospective, multicenter observational cohort study of 1221 participants of African descent and European descent with no glaucoma (normal), suspected glaucoma, and glaucoma. Six hundred eighty-six patient participants in the African Descent and Glaucoma Evaluation Study will be followed up longitudinally. Four hundred thirty-six participants of European descent from the Diagnostic Innovations in Glaucoma Study (DIGS) were also included. Baseline demographics, visual function (standard automated perimetry, short-wavelength automated perimetry, frequency doubling technology perimetry), optic nerve structure (retina tomography, optical coherence tomography), clinical status, and risk factors were measured. RESULTS Individuals of African descent had (1) thinner corneas (P < .001) across all diagnostic groups, (2) a higher percentage of reported diabetes mellitus (P < .001) and high blood pressure (P < .001) and a lower percentage of reported heart disease (P = .001), and (3) worse pattern standard deviation for standard automated perimetry fields overall (P = .001) and within normal limits (P = .01) than individuals of European descent. No differences were present for mean intraocular pressure (P = .79). CONCLUSIONS Significant baseline differences were found in a number of clinical findings between persons of African descent compared with European descent. Longitudinal data from the African Descent and Glaucoma Evaluation Study will be important for determining which baseline features are important and predictive for accurate diagnosis and follow-up in this high-risk group. Trial Registration clinicaltrials.gov Identifier: NCT00221923.

Prediction of Functional Loss in Glaucoma From Progressive Optic Disc Damage

OBJECTIVE To evaluate the ability of progressive optic disc damage detected by assessment of longitudinal stereophotographs to predict future development of functional loss in those with suspected glaucoma. METHODS The study included 639 eyes of 407 patients with suspected glaucoma followed up for an average of 8.0 years with annual standard automated perimetry visual field and optic disc stereophotographs. All patients had normal and reliable standard automated perimetry results at baseline. Conversion to glaucoma was defined as development of 3 consecutive abnormal visual fields during follow-up. Presence of progressive optic disc damage was evaluated by grading longitudinally acquired simultaneous stereophotographs. Other predictive factors included age, intraocular pressure, central corneal thickness, pattern standard deviation, and baseline stereophotograph grading. Hazard ratios for predicting visual field loss were obtained by extended Cox models, with optic disc progression as a time-dependent covariate. Predictive accuracy was evaluated using a modified R(2) index. RESULTS Progressive optic disc damage had a hazard ratio of 25.8 (95% confidence interval, 16.0-41.7) and was the most important risk factor for development of visual field loss with an R(2) of 79%. The R(2)s for other predictive factors ranged from 6% to 26%. CONCLUSIONS Presence of progressive optic disc damage on stereophotographs was a highly predictive factor for future development of functional loss in glaucoma. These findings suggest the importance of careful monitoring of the optic disc appearance and a potential role for longitudinal assessment of the optic disc as an end point in clinical trials and as a reference for evaluation of diagnostic tests in glaucoma.