Faculty Bibliography

BACKGROUND AND OBJECTIVE: Optical coherence tomography (OCT) is able to determine the optic disc margin automatically. The aim of this study was to investigate the accuracy of the automatic OCT optic nerve head measurements in the presence of peripapillary atrophy. PATIENTS AND METHODS: This was a cross-sectional, retrospective study. Thirty-one subjects with peripapillary atrophy underwent optic nerve head scanning with OCT version 3. Nineteen of the eyes were classified clinically as having glaucoma, nine had suspected glaucoma, and three were normal. Automatic OCT results were compared with manual tracing results. RESULTS: Significant differences were found between most OCT optic nerve head automated and manual disc assessment parameters; however, good agreement was found between the two methods for all parameters (intraclass correlation, 0.71 to 0.94). Areas under receiver operator characteristics curves for clinical status were similar for all parameters with both methods. CONCLUSION: Automated OCT optic nerve head analysis may be used in the clinical setting in the presence of peripapillary atrophy; however, caution should be used when comparing individual results with population-derived optic nerve head results.

PURPOSE: To evaluate pulsatile ocular blood flow (POBF) analysis in normal subjects and glaucoma patients by comparison of POBF measurements with functional (as determined by visual field [VF]) and structural (as determined by optical coherence tomography [OCT]) measures. DESIGN: Prospective, cross-sectional study. METHODS: Forty-one eyes of 24 consecutive glaucoma patients and 20 eyes of 10 healthy subjects were studied; POBF analysis was performed on all subjects at the same visit as VF testing and OCT retinal nerve fiber layer (NFL) thickness measurement. The mean results of normal and glaucomatous eyes were compared for each method. Correlation between measurements obtained with each modality and the discriminating power using receiver operator characteristic curves was tested. RESULTS: The mean POBF (standard deviation [SD]) in the normal group was 1,010.4 (292.8) microl/min and 989.3 (305.5) microl/min in the glaucoma group (P =.90). Significant differences between groups were found for VF mean deviation and pattern standard deviation (P =.02, P =.004, respectively) and OCT mean NFL thickness (P <.0001). No correlation was found between POBF parameters and intraocular pressure, VF, or OCT variables except for intraocular pressure in glaucoma group (r = -.43, P =.003). The area under the receiver operator characteristic curves was higher for VF indexes and OCT mean NFL thickness than POBF parameters for distinguishing between normal and glaucomatous eyes. CONCLUSIONS: The wide range of normal values and the low discriminating power of POBF between normal and glaucomatous eyes limits the clinical use of the device for glaucoma patients.

PURPOSE: To assess changes in retinal nerve fiber layer (NFL) thickness in glaucoma patients after filtration surgery by using optical coherence tomography (OCT). DESIGN: Retrospective observational case series. PARTICIPANTS: Thirty-eight eyes of 31 glaucoma patients who underwent trabeculectomy or a combined procedure of cataract extraction and trabeculectomy were evaluated retrospectively. METHODS: Eyes were imaged with OCT before surgery (1 week to 6 months before surgery; mean +/- standard deviation [SD], 71.3 +/- 61.2 days) and after surgery (6-12 months after surgery; 247.2 +/- 63.5 days) to measure peripapillary NFL thickness. MAIN OUTCOME MEASURES: Changes in mean and segmental NFL thickness with respect to age, postoperative change in intraocular pressure (IOP), preoperative visual field test global indices, and change in visual field global indices. RESULTS: A significant increase in the overall mean NFL thickness was present after surgery (P < 0.0001). Segmental analysis found a significant increase in NFL thickness in the nasal, superior, and temporal quadrants. IOP decreased after surgery from 22.0 +/- 6.4 mmHg to 11.4 +/- 4.7 mmHg (mean +/- SD). Twenty-eight (73.7%) of 38 eyes had an IOP reduction >30%. The mean NFL thickness increase (0.5- microm/mmHg decrease of IOP) was significantly correlated with the IOP reduction (r = -0.41; P = 0.03). No correlation was found between NFL thickness changes and age, preoperative visual field global indices, or change in visual field global indices. CONCLUSIONS: A significant increase of the mean NFL thickness, which was related to IOP reduction, was detected after glaucoma filtration surgery.

PURPOSE: To compare computer-assisted planimetry using the Discam system (Marcher Enterprises Ltd., Hereford, UK), confocal scanning laser ophthalmoscopy (CSLO), and stereoscopic disc photography with respect to optic nerve head (ONH) measurements and glaucoma status. DESIGN: Comparative, observational case series and interobserver variability study. METHODS: Three hundred eighty-six eyes of 233 consecutive subjects were imaged with the Discam, and a subset underwent ONH evaluation with CSLO (n = 297), stereoscopic photography (n = 233), or both. Subjects were classified into normal, glaucoma suspect, and glaucoma groups based on clinical findings of slit-lamp disc examination and visual field testing. Agreement of cup-to-disc ratio measurements among the three technologies was assessed by the intraclass correlation coefficient (ICC) and areas under the receiver operator characteristic (AROC) curves. MAIN OUTCOME MEASURES: Cup-to-disc ratio as measured by Discam, CSLO, and stereography. RESULTS: Intraclass correlation coefficients calculated using the two-way random effects model for comparing Discam, CSLO, and stereography among cup-to-disc area ratio, vertical cup-to-disc ratio, and horizontal cup-to-disc ratio were 0.46 to 0.53. The ICC was higher for eyes with larger optic discs (0.51) than those with smaller ones (0.32). The ICC calculated using the fixed effects model for the Discam and CSLO comparison was 0.72. Areas under the receiver operator characteristic curves were 0.67 to 0.80 among the three technologies comparing normal with glaucomatous eyes. In general, there was no statistically significant difference between techniques with respect to sensitivity and specificity of glaucoma detection. CONCLUSIONS: There is good agreement between ONH measurements obtained by Discam, CSLO, and stereography; however, the results are not interchangeable. Similar AROC curve values among all three techniques imply that the Discam, CSLO, and stereography perform equally for the determination of glaucoma status.

PURPOSE: To evaluate macular volume in normal and glaucomatous eyes using optical coherence tomography (OCT). DESIGN: Case control study. METHOD: The authors assessed 272 eyes of 164 subjects as part of an institutional study at New England Eye Center in Boston, Massachusetts; 202 eyes were in the study group and 70 eyes in the control group. Eyes were categorized as normal (70 eyes of 43 subjects), glaucoma suspect (70 eyes of 44 subjects), early glaucoma (70 eyes of 47 subjects), or advanced glaucoma (62 eyes of 43 subjects). Subjects underwent analysis with the commercially available OCT1 unit. Optical coherence tomography macular neurosensory retinal thickness maps were used to calculate macular volume for comparison to Humphrey visual field testing, intraocular pressure measurement, and stereo biomicroscopy of the optic nerve head and nerve fiber layer. RESULTS: Using repeated measures regression, macular volume in normal (2.37 +/- 0.11 mm(3)) glaucoma suspect (2.33 +/- 0.16 mm(3)), and early glaucoma eyes (2.27 +/- 0.13 mm(3)) was significantly greater than in eyes with advanced glaucoma (2.12 +/- 0.23 mm(3), P =.0001, P =.0001, and P =.0008, respectively). Macular volume in normal eyes was significantly greater than in early glaucoma eyes (P =.01). CONCLUSIONS: Optical coherence tomography retinal macular volume correlates with known structural defects of glaucoma, providing a potential objective and quantitative parameter for evaluation. Our data show a significant difference in macular volume between normal, glaucoma suspect, and early glaucoma eyes, compared with advanced glaucomatous eyes as well as between normal and early glaucomatous eyes. This correlates with a trend of decreasing macular volume in eyes with more advanced disease.

PURPOSE: Elevated intraocular pressure (IOP), the major causal risk factor for glaucoma, often decreases after cataract removal by phacoemulsification ultrasound. In this study, the hypothesis that ultrasound energy propagated through a fluid medium induces a stress response with the potential to lower IOP was investigated. METHODS: Normal and glaucomatous trabecular meshwork (TM) cell culture lines were initiated from tissue isolated from human cadaveric eyes or trabeculectomy specimens. Cultured cells were treated for 60 seconds with a phacoemulsification ultrasound probe set to a power of 70%. Activation of the TM cell-specific stress response was assayed by enzyme-linked immunosorbent assay (ELISA) and immunolocalization. RESULTS: Normal TM cell cultures did not release detectable levels of the stress response protein, IL-1alpha, into their culture medium. In contrast, IL-1alpha was easily detected after treatment with ultrasound energy. Consistent with earlier findings, glaucomatous TM cells produced IL-1alpha constitutively, and the level of expression was increased after treatment with phacoemulsification ultrasound. As was previously demonstrated, the stress-regulated transcription factor NF-kappaB was present in the cytoplasm of normal cells, but in the nucleus of glaucomatous cells. After treatment with ultrasound energy, NF-kappaB translocated to the nucleus in the normal cells. Endothelial leukocyte-adhesion molecule (ELAM)-1 was not detected in normal TM cells, but was constitutively present on glaucomatous TM cells, consistent with findings in previous work. ELAM-1 expression was induced in normal cells by ultrasound treatment. CONCLUSIONS: A potentially IOP-lowering stress response is induced in TM cells by ultrasound. The findings suggest that this response may be induced clinically during cataract removal by phacoemulsification, and may be one mechanism responsible for the reduction in IOP that often follows this procedure.

BACKGROUND AND OBJECTIVE: To describe the changes revealed by multifocal electroretinography (ERG) in patients taking hydroxychloroquine. PATIENTS AND METHODS: Six patients being treated for various inflammatory conditions with hydroxychloroquine for periods ranging from 8 months to 7 years were consecutively evaluated. Each examination included measurement of Snellen visual acuities, Amsler grid assessment, and automated visual field testing. In some cases, funduscopic examinations were complimented by photography and fluorescein angiography. Multifocal ERG was performed for all patients. RESULTS: Three patients (six eyes) were found to have distinctive abnormalities on multifocal ERG consisting of pericentral depression of ERG signals. The abnormalities on multifocal ERG corresponded with the patients' subjective descriptions and the visual field depiction of their pericentral scotomas. All affected patients had been taking hydroxychloroquine for at least 7 years. One patient with generalized depression on multifocal ERG had possible hydroxychloroquine retinopathy. Two patients (three eyes) had relatively normal results on multifocal ERG. CONCLUSION: Multifocal ERG objectively demonstrates depression of signals in the perifoveal region in visually symptomatic patients with long-term hydroxychloroquine use. Even patients with normal visual acuity and no fundus abnormalities can have abnormal results. Although we have not yet identified patients with abnormalities on multifocal ERG before the onset of symptoms, multifocal ERG may be useful in monitoring patients at risk and may provide an earlier opportunity to identify maculopathy.