Faculty Bibliography

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.

A case of rhegmatogenous retinal detachment complicated by Schwartz's syndrome following Nd:YAG laser peripheral iridectomy in the management of pigmentary glaucoma is described. A 36-year-old man underwent Nd:YAG laser peripheral iridectomy for pigmentary glaucoma. Three days later, he had a rhegmatogenous retinal detachment. The break remained open following scleral buckling with persistent subretinal fluid, "iridocyclitis," and elevated intraocular pressure. Two months later, the patient underwent revision of the scleral buckle. Following closure of the retinal break, the retina flattened, and within 2 weeks the "iridocyditis" resolved and the intraocular pressure decreased to approximately 20 mm Hg. Rhegmatogenous retinal detachment may occur following laser peripheral iridectomy, and suggests the necessity for a prospective dinical trial to evaluate the role of laser peripheral iridectomy in the management of pigmentary glaucoma.

PURPOSE: To evaluate the relationship between optic nerve head (ONH) measurements generated by optical coherence tomography (OCT; versions 2 and 3) and confocal scanning laser ophthalmoscopy (CSLO) and to compare the association between OCT and CSLO ONH measurements with glaucoma disease status, as determined by clinical evaluation and perimetry. DESIGN: Cross-sectional study. METHODS: In a prospective study in the glaucoma service of an academic department of ophthalmology, 159 eyes (97 subjects) and 77 eyes (44 subjects) were recruited in two separate periods. All subjects were scanned with a CSLO device. Subjects tested within the first period of recruitment were scanned with OCT version 2 and in the second period with OCT version 3. The main outcome measure was the correlation between automatic and manually defined OCT ONH measurements and the correlation of CSLO and OCT ONH measurements between devices and with glaucoma disease status. RESULTS: A high correlation was found between ONH measurements obtained by the automatic determination of ONH margin and those obtained by manual tracing of the disk margin (r =.93 to.98). Optical coherence tomography and CSLO ONH measurements were highly correlated. Optical coherence tomography-measured mean disk area was significantly larger than that measured by CSLO, as were all other disk size-related parameters. The areas under the receiver operator characteristic (AROC) curves for the associations between CSLO and OCT ONH measurements and clinical diagnosis were found to be similar and in the range of 0.47 to 0.79 for both devices. CONCLUSIONS: Automated OCT ONH measurements correlate highly with those obtained by manual tracing of disk margin. Optical coherence tomography and CSLO ONH analyses are highly correlated and have similar associations with glaucoma disease status.

PURPOSE: To evaluate the hypothesis that macular thickness correlates with the diagnosis of glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: We studied 367 subjects (534 eyes), including 166 eyes of 109 normal subjects, 83 eyes of 58 glaucoma suspects, 196 eyes of 132 early glaucoma patients, and 89 eyes of 68 advanced glaucoma patients. METHODS: We used optical coherence tomography (OCT) to measure macular and nerve fiber layer (NFL) thickness and to analyze their correlation with each other and with glaucoma status. We used both the commercial and prototype OCT units and evaluated correspondence between measurements performed on the same eyes on the same days. MAIN OUTCOME MEASURE: Macular and NFL thickness as measured by OCT. RESULTS: All NFL parameters both in prototype and commercial OCT units were statistically significantly different comparing normal subjects and either early or advanced glaucoma (P < 0.001). Inner ring, outer ring, and mean macular thickness both in prototype and commercial OCT devices were found to be significantly different between normal subjects and advanced glaucomatous eyes (P < 0.001). The outer ring was the only macular parameter that could significantly differentiate between normal and early glaucoma with either the prototype or commercial OCT unit (P = 0.003, P = 0.008, respectively). The area under the receiver operator characteristic (AROC) curves comparing mean NFL thickness between normal and advanced glaucomatous eyes was 1.00 for both the prototype and commercial OCT devices for eyes scanned on both machines on the same day. The AROC comparing mean macular thickness in normal and advanced glaucomatous eyes scanned on both machines on the same day was 0.88 for the prototype OCT device and 0.80 for the commercial OCT. CONCLUSIONS: Both macular and NFL thickness as measured by OCT showed statistically significant correlations with glaucoma, although NFL thickness showed a stronger association than macular thickness. There was good correspondence between findings using both the prototype and commercial OCT units. Macular and NFL thickness measurements made with OCT may have usefulness in the clinical assessment of glaucoma.