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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 μm/y vs. 0.14 μm/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.

Purpose-To investigate whether long-term intraocular pressure (IOP) fluctuations are a risk factor for conversion from ocular hypertension to glaucoma. Design-Observational cohort study.Participants-The study included 252 eyes of 126 patients with ocular hypertension observed untreated as part of the Diagnostic Innovations in Glaucoma Study. At baseline, ocular hypertensive eyes had elevated IOP, normal visual fields (VFs) on standard automated perimetry, and normal optic discs as evaluated by stereophotograph assessment.Methods-Glaucoma conversion was defined as development of reproducible VF loss or optic disc damage. Analyses included all IOP measurements from the baseline visit to time of progression (for converters) and last follow-up (for nonconverters). Mean IOP and IOP fluctuation were calculated as the arithmetic mean and standard deviation (SD), respectively, of all available IOP measurements per eye.Main Outcome Measures-Univariable and multivariable Cox regression analyses were used to evaluate the association between IOP fluctuation and time to progression. Multivariable models adjusted for age, mean IOP, central corneal thickness, vertical cup-to-disc ratio, and pattern SD.Results-Forty eyes of 31 subjects developed glaucoma during follow-up. Mean IOPs during follow-up were 25.4±4.2 mmHg for the eyes that converted to glaucoma and 24.1±3.5 mmHg for the eyes that did not. Corresponding values for IOP fluctuation were 3.16±1.35 mmHg and 2.77±1.11 mmHg, respectively. Intraocular pressure fluctuation was not a risk factor for conversion to glaucoma both in univariable analysis (hazard ratio [HR], 1.30 per 1 mmHg higher; 95% confidence interval [CI], 0.76-1.96; P = 0.092) and in multivariable analysis (adjusted HR, 1.08 per 1 mmHg higher; 95% CI, 0.79-1.48; P = 0.620). Mean IOP during follow-up was a significant risk factor for progression both in univariable analysis (HR = 1.16 per 1 mmHg higher; 95% CI, 1.04-1.31; P = 0.010) and in multivariable analysis (adjusted HR, 1.20 per 1 mmHg higher; 95% CI, 1.06-1.36; P = 0.005).Conclusion-Long-term IOP fluctuations do not appear to be significantly associated with the risk of developing glaucoma in untreated ocular hypertensive subjects.Although elevated intraocular pressure (IOP) has been unquestionably demonstrated to be a risk factor for development and progression of glaucoma, 1-5 there has been controversy with regard to the IOP features that are the most relevant. Long-term (i.e., visit Both the AGIS and EMGT included only patients with definite glaucoma diagnosis at baseline. It is possible that the role of long-term IOP fluctuation as a risk factor for glaucoma development could be different than that for glaucoma progression. Two recent multicenter prospective randomized clinical trials reported on the predictive factors for conversion from ocular hypertension to glaucoma. In both the Ocular Hypertension Treatment Study 11 and the European Glaucoma Prevention Study, 12 higher IOP levels at the baseline visits were associated with a higher ...

Purpose To evaluate the relationship between glaucomatous structural damage assessed by the Cirrus Spectral Domain OCT (SDOCT) and functional loss as measured by standard automated perimetry (SAP). Methods Four hundred twenty two eyes (78 healthy, 210 suspects, 134 glaucomatous) of 250 patients were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS) and from the African Descent and Glaucoma Evaluation Study (ADAGES). All eyes underwent testing with the Cirrus SDOCT and SAP within a 6-month period. The relationship between parapapillary retinal nerve fiber layer thickness (RNFL) sectors and corresponding topographic SAP locations was evaluated using locally weighted scatterplot smoothing (LOWESS) and regression analysis. SAP sensitivity values were evaluated using both linear as well as logarithmic scales. We also tested the fit of a model (Hood) for structure-function relationship in glaucoma. Results Structure was significantly related to function for all but the nasal thickness sector. The relationship was strongest for superotemporal RNFL thickness and inferonasal sensitivity (R2 = 0.314, P<0.001). The Hood model fitted the data relatively well with 88% of the eyes inside the 95% confidence interval predicted by the model. Conclusion RNFL thinning measured by the Cirrus SDOCT was associated with correspondent visual field loss in glaucoma.

Purpose-To evaluate the relationship between intraocular pressure (IOP) and progressive retinal nerve fiber layer (RNFL) loss, as measured by scanning laser polarimetry with enhanced corneal compensation (GDx ECC), in a cohort of glaucoma patients and individuals suspected of having the disease followed over time. Design-Observational cohort study.Participants-The study included 344 eyes of 204 patients recruited from the Diagnostic Innovations in Glaucoma Study (DIGS). There were 98 eyes (28%) with a diagnosis of glaucoma and 246 (72%) were considered glaucoma suspects at baseline.Methods-Images were obtained annually with the GDx ECC scanning laser polarimeter, along with stereophotographs and SAP. The study included a total of 1211 GDx ECC visits with an average of 3.5 visits per eye. Progression was determined by the Guided Progression Analysis software for SAP and by masked assessment of stereophotographs performed by expert graders.Main Outcome Measures-Random coefficient models were used to evaluate the relationship between IOP and RNFL thickness measurements over time in progressors and nonprogressors. Models were adjusted for baseline diagnosis and central corneal thickness.Results-For all 344 eyes, the overall rate of change for the GDx ECC average thickness at an average IOP of 17 mmHg was −0.25 μm per year (P = 0.002). Each 1-mmHg higher IOP was associated with an additional loss of 0.05 μm per year of RNFL (P = 0.001). Twenty-nine eyes (8%) showed progression on SAP and/or optic disc stereophotographs. These eyes had a significantly higher rate of RNFL change (−0.95μm/year) than nonprogressors (−0.17 μm/year; P = 0.001). For progressors, each 1-mmHg higher IOP was associated with an additional loss of 0.13 μm per year of RNFL.Conclusions-Higher levels of IOP during follow-up were significantly related to higher rates of progressive RNFL loss detected by the GDx ECC. These findings suggest that the GDx ECC may be helpful in monitoring progression and estimating rates of change in patients with glaucoma or suspected of having the disease. Also, they may contribute to a better understanding of the relationship between IOP and structural deterioration in glaucoma. NIH Public Access Author ManuscriptOphthalmology. Author manuscript; available in PMC 2010 June 1. Published in final edited form as:Ophthalmology. 2009 June ; 116(6): 1125-33.e1-3. doi:10.1016/j.ophtha.2008.12.062. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptSeveral prospective clinical trials have provided compelling evidence for the role of intraocular pressure (IOP) as the main risk factor for development and progression of glaucoma. [1][2][3][4][5][6] In the Ocular Hypertension Treatment Study (OHTS), IOP-lowering therapy was associated with a 54% relative reduction in the risk of developing primary open-angle glaucoma during followup. 7 For disease progression, the Early Manifest Glaucoma Trial showed that each 1-mmHg higher mean IOP during follow-up was associated with a 12% increase in the chance o...

Purpose To evaluate the ability of scanning laser polarimetry with variable corneal compensation to detect progressive retinal nerve fiber layer (RNFL) loss in glaucoma patients and patients suspected of having the disease. Methods This was an observational cohort study that included 335 eyes of 195 patients. Images were obtained annually with the GDx VCC scanning laser polarimeter, along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. The median follow-up time was 3.94 years. Progression was determined using commercial software for SAP and by masked assessment of optic disc stereophotographs performed by expert graders. Random coefficient models were used to evaluate the relationship between RNFL thickness measurements over time and progression as determined by SAP and/or stereophotographs. Results From the 335 eyes, 34 (10%) showed progression over time by stereophotographs and/or SAP. Average GDx VCC measurements decreased significantly over time for both progressors as well as non-progressors. However, the rate of decline was significantly higher in the progressing group (−0.70 μm/year) compared to the non-progressing group (−0.14 μm/year; P = 0.001). Black race and male sex were significantly associated with higher rates of RNFL loss during follow-up. Conclusions The GDx VCC scanning laser polarimeter was able to identify longitudinal RNFL loss in eyes that showed progression in optic disc stereophotographs and/or visual fields. These findings suggest that this technology could be useful to detect and monitor progressive disease in patients with established diagnosis of glaucoma or suspected of having the disease.

Purpose-To compare retinal nerve fiber layer (RNFL) and optic disc topographic imaging for detection of optic nerve damage in patients suspected of having glaucoma. Design-Observational cohort study.Participants-A cohort of 82 patients suspected of having glaucoma based on the appearance of the optic nerve.Methods-All patients were imaged using the GDx VCC scanning laser polarimeter and HRT (software version 3.0) confocal scanning laser ophthalmoscope. All patients had normal standard automated perimetry visual fields at the time of imaging and were classified based on history of documented stereophotographic evidence of progressive glaucomatous change in the appearance of the optic nerve occurring before the imaging sessions.Main Outcome Measures-Areas under the receiver operating characteristic (ROC) curves were used to evaluate the diagnostic accuracies of GDx VCC and the HRT.Results-Forty eyes with progressive glaucomatous optic nerve change were included in the glaucoma group, and 42 eyes without any evidence of progressive damage to the optic nerve followed untreated for an average time of 8.97±3.08 years were included in the normal group. The area under the ROC curve for the best parameter from GDx VCC (nerve fiber indicator [NFI]) was significantly larger than that of the best parameter from the HRT (rim volume) (0.83 vs. 0.70; P = 0.044). The NFI parameter also had a larger ROC curve area than that of the contour line-independent parameter glaucoma probability score (0.83 vs. 0.68; P = 0.023). Assuming borderline results as normal, the Moorfields regression analysis classification had a sensitivity of 48% for specificity of 69%. For a similar specificity (70%), the parameter NFI had a significantly larger sensitivity (83%) (P = 0.003).Conclusions-Retinal nerve fiber layer imaging with GDx VCC had a superior performance versus topographic optic disc assessment with the HRT for detecting early damage in patients suspected of having glaucoma. For glaucoma diagnosis, these results suggest that GDx VCC may offer advantage over the HRT when these tests are combined with clinical examination of the optic nerve.To diagnose disease, a clinician integrates the constellation of symptoms and/or signs of a presenting patient and then assigns a level of certainty regarding its presence. In the case of glaucoma evaluation, the process generally starts with the medical interview and history. It is NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript followed by clinical examination, which generally includes slit-lamp examination, intraocular pressure (IOP) measurement, and optic nerve examination. After this information is collected, the clinician hypothesizes about the chance that glaucoma is present and can order additional tests, such as the visual field (VF).It is not unusual for a patient to present with suspicious appearance of the optic disc and normal or inconclusive VF tests. In this situation, additional testing, such as optic disc and/or retinal nerve fiber layer (RNFL) imaging,...

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