David S. Greenfield

Effect of Corneal Polarization Axis on Assessment of Retinal Nerve Fiber Layer Thickness by Scanning Laser Polarimetry

PURPOSE Scanning laser polarimetry uses an anterior segment compensating device that assumes a fixed axis of corneal birefringence, which we call the corneal polarization axis. The purpose of this investigation was to establish the distribution of corneal polarization axes among a population of normal eyes and to evaluate the relationship between corneal polarization axis and posterior segment retardation. METHODS We constructed a noninvasive slit lamp-mounted device incorporating two crossed linear polarizers and an optical retarder in order to measure the slow axis of corneal birefringence. Normal subjects underwent corneal polarization axis measurement. A subset of eyes underwent scanning laser polarimetry of the peripapillary retinal nerve fiber layer (n = 32) and macula (n = 29), and retardation measurements were evaluated in each group. RESULTS One hundred eighteen eyes of 63 normal subjects (35 female, 28 male) underwent corneal polarization axis measurement (mean age, 45.5 +/- 17.1 years). Six eyes (5.1%) demonstrated unmeasurable corneal polarization. In the remaining 112 eyes, the mode of the corneal polarization axis distribution was 10 to 20 degrees nasally downward (range, 90 degrees nasally downward to 54 degrees nasally upward). A significant (P <.0001) correlation was observed between fellow eyes (R(2) =.52), with a mean difference of 11.2 +/- 10.5 degrees (range, 0-52 degrees). Corneal polarization axis was significantly associated (R(2) =.52-.84) with retinal nerve fiber layer and macula summary retardation parameters (average thickness, ellipse average, superior and inferior average, superior and total integral; P <.0001 for all groups). CONCLUSIONS The mean corneal polarization axis among normal corneas is nasally downward; however, considerable intraindividual and interindividual variability exists. The linear relationship between corneal polarization axis and posterior segment retardation parameters is responsible, in part, for the wide distribution of retinal nerve fiber layer thickness data generated by scanning laser polarimetry.

Optical coherence tomography and scanning laser polarimetry in normal, ocular hypertensive, and glaucomatous eyes

PURPOSE To evaluate the relationship between visual function and retinal nerve fiber layer measurements obtained with scanning laser polarimetry and optical coherence tomography in a masked, prospective trial. METHODS Consecutive normal, ocular hypertensive, and glaucomatous subjects who met inclusion and exclusion criteria were evaluated. Complete ophthalmologic examination, disk photography, scanning laser polarimetry, optical coherence tomography, and automated achromatic perimetry were performed. RESULTS Seventy-eight eyes of 78 patients (17 normal, 23 ocular hypertensive, and 38 glaucomatous) were enrolled (mean age, 56.8+/-11.5 years; range, 26 to 75 years). Eyes with glaucoma had significantly greater neural network scores on scanning laser polarimetry and lower maximum modulation, ellipse modulation, and mean retinal nerve fiber layer thickness measured with optical coherence tomography compared with normal and ocular hypertensive eyes, respectively (all P<.005). Significant associations were observed between neural network number (r = -.51, r = .03), maximum modulation (r = .39, r = -.32), ellipse modulation (r = .36, r = -.28), and optical coherence tomography-generated retinal nerve fiber layer thickness (r = .68, r = -.59) and visual field mean deviation and corrected pattern standard deviation, respectively. All scanning laser polarimetry parameters were significantly associated with optical coherence tomography-generated retinal nerve fiber layer thickness. CONCLUSION Optical coherence tomography and scanning laser polarimetry were capable of differentiating glaucomatous from nonglaucomatous populations in this cohort; however considerable measurement overlap was observed among normal, ocular hypertensive, and glaucomatous eyes. Retinal nerve fiber layer structural measurements demonstrated good correlation with visual function, and retinal nerve fiber layer thickness by optical coherence tomography correlated with retardation measurements by scanning laser polarimetry.

Heidelberg retina tomography and optical coherence tomography in normal, ocular-hypertensive, and glaucomatous eyes

PURPOSE To evaluate optic disc and retinal nerve fiber layer (RNFL) appearance in normal, ocular-hypertensive, and glaucomatous eyes undergoing confocal scanning laser ophthalmoscopy and optical coherence tomography (OCT). DESIGN Prospective, cross-sectional study. PARTICIPANTS Seventy-eight eyes of 78 consecutive normal (n = 17), ocular-hypertensive (n = 23), and glaucomatous subjects (n = 38) were enrolled. METHODS Each patient underwent complete ophthalmic examination, achromatic automated perimetry, confocal scanning laser ophthalmoscopy (Heidelberg Retinal Tomography [HRT]), and OCT. Topographic HRT parameters (disc area, cup-disc ratio, rim area, rim volume, cup shape measure, mean RNFL thickness, and cross-sectional area) and mean OCT-generated RNFL thickness were evaluated in each group. MAIN OUTCOME MEASURES OCT and HRT assessment of optic disc and RNFL anatomy. RESULTS OCT RNFL thickness showed no difference between normal and ocular-hypertensive eyes (P = 0.15) but was significantly less in glaucomatous eyes (P < 0.001). HRT measurements of rim area, cup-disc ratio, cup shape measure, RNFL thickness, and RNFL cross-sectional area were significantly less in glaucomatous eyes (all P < 0.005) and were correlated with mean OCT RNFL thickness (all P < 0.02). RNFL thickness using OCT or HRT was highly correlated with visual field mean defect during achromatic perimetry (P < 0.0001). CONCLUSION Both HRT and OCT can differentiate glaucomatous from nonglaucomatous eyes. RNFL thickness measurements using OCT correspond to disc topographic parameters using HRT.

A Randomized Trial of Brimonidine Versus Timolol in Preserving Visual Function: Results From the Low-pressure Glaucoma Treatment Study

PURPOSE To compare the alpha2-adrenergic agonist brimonidine tartrate 0.2% to the beta-adrenergic antagonist timolol maleate 0.5% in preserving visual function in low-pressure glaucoma. DESIGN Randomized, double-masked, multicenter clinical trial. METHODS Exclusion criteria included untreated intraocular pressure (IOP) >21 mm Hg, visual field mean deviation worse than -16 decibels, or contraindications to study medications. Both eyes received twice-daily monotherapy randomized in blocks of 7 (4 brimonidine to 3 timolol). Standard automated perimetry and tonometry were performed at 4-month intervals. Main outcome measure was field progression in either eye, defined as the same 3 or more points with a negative slope ≥-1 dB/year at P<5%, on 3 consecutive tests, assessed by pointwise linear regression. Secondary outcome measures were progression based on glaucoma change probability maps (GCPM) of pattern deviation and the 3-omitting method for pointwise linear regression. RESULTS Ninety-nine patients were randomized to brimonidine and 79 to timolol. Mean (± SE) months of follow-up for all patients was 30.0 ± 2. Statistically fewer brimonidine-treated patients (9, 9.1%) had visual field progression by pointwise linear regression than timolol-treated patients (31, 39.2%, log-rank 12.4, P=.001). Mean treated IOP was similar for brimonidine- and timolol-treated patients at all time points. More brimonidine-treated (28, 28.3%) than timolol-treated (9, 11.4%) patients discontinued study participation because of drug-related adverse events (P=.008). Similar differences in progression were observed when analyzed by GCPM and the 3-omitting method. CONCLUSION Low-pressure glaucoma patients treated with brimonidine 0.2% who do not develop ocular allergy are less likely to have field progression than patients treated with timolol 0.5%.

Trabeculectomy with intraoperative mitomycin C versus 5-Fluorouracil: Prospective randomized clinical trial

OBJECTIVE To evaluate the relative efficacy and safety of 5-fluorouracil (5-FU) and mitomycin C (MMC) when used as adjuncts with primary trabeculectomy in eyes not at high risk for failure. DESIGN Prospective multicenter, randomized clinical trial. PARTICIPANTS One hundred thirteen patients with primary open-angle, pseudoexfoliative, pigmentary, or angle-closure glaucoma undergoing primary trabeculectomy were recruited. METHODS One eye of each patient was randomized to receive either 5-FU (50 mg/ml for 5 minutes) or MMC (0.4 mg/ml for 2 minutes). MAIN OUTCOME MEASURES Intraocular pressure (IOP), visual acuity, complications, and interventions were documented at fixed intervals after surgery. The study also examined progression of visual field loss, long-term complications, and bleb appearance 3 years after surgery. RESULTS Of the 108 patients with complete perioperative information, 54 eyes received 5-FU and 54 received MMC. The proportion of patients reaching different predefined target IOPs after surgery was slightly higher in the MMC group than in the 5-FU group. This difference was less than 25%, which would have been necessary to achieve statistical significance with a power of 0.8 and the sample size used. Likewise, there was no statistically significant difference between the groups with regard to mean preoperative IOP, complications, or interventions. Mean postoperative follow-up was 309 and 330 days in the 5-FU and MMC groups, respectively (P = 0.593). CONCLUSIONS 5-Fluorouracil and MMC were found to be equally safe and effective adjuncts to primary trabeculectomy in the short- and medium-term postoperative periods.

Presumed topiramate-induced bilateral acute angle-closure glaucoma

PURPOSE We describe a case of bilateral angle-closure glaucoma associated with oral topiramate therapy. METHODS Interventional case report. Case report with echographic illustration. RESULTS A 51-year-old man developed bilateral acute angle-closure glaucoma 2 weeks after beginning topiramate therapy for bipolar affective disorder. Laser peripheral iridotomy was performed in the right eye without resolution of the acute attack. Echography revealed lens thickening and ciliochoroidal detachments in both eyes. Visual acuity, intraocular pressure, and anterior and posterior segment anatomy normalized 2 weeks after cessation of topiramate therapy. CONCLUSION Topiramate, a new sulfa-derivative antiepileptic medication, may cause idiosyncratic ciliochoroidal detachments and ciliary body edema leading to anterior displacement of the lens-iris diaphragm, lens thickening, and acute angle-closure glaucoma.

Increasing Sampling Density Improves Reproducibility of Optical Coherence Tomography Measurements

PURPOSE Published series of peripapillary retinal nerve fiber layer (RNFL) measurements using optical coherence tomography (OCT) have sampled 100 evenly distributed points on a 360 degrees peripapillary circular scan. The goal of this study was to determine whether a four-fold increase in sampling density improves the reproducibility of OCT measurements. METHODS Complete ophthalmic examinations, achromatic automated perimetry, and OCT imaging were performed in all patients. The OCT scanning consisted of three superior and inferior quadrantic scans (100 sampling points/quadrant) and three circular scans (25 points/quadrant). The RNFL thickness measurements and coefficient of variation (CV) were calculated for the superior and inferior quadrants for each sampling density technique. RESULTS The study included 22 eyes of 22 patients (3 control subjects; 2 patients with ocular hypertension; and 17 patients with glaucoma). Quadrants with associated glaucomatous visual field loss on automated achromatic perimetry had thinner RNFLs than quadrants without functional defects for both the 25- and 100-points/quadrant scans. For quadrants associated with normal visual hemifields (n = 22), there was no difference between the 25- and 100-points/quadrant scans in mean RNFL thickness and CV. Among quadrants with visual field defects (n = 22), RNFL thickness measurements were thinner in the 25-points/quadrant scans than in the 100-points/quadrant scans. The CV for the 25-points/quadrant scans (25.9%) was significantly higher than that for the 100-points/quadrant scans (11.9%). CONCLUSION Increasing the sampling density of OCT scans provides less variable representation of RNFL thickness. The optimal sampling density to achieve maximal reliability of OCT scans remains to be determined.

Scanning laser polarimetry with variable corneal compensation and optical coherence tomography in normal and glaucomatous eyes

PURPOSE To evaluate the relationship between visual function and retinal nerve fiber layer (RNFL) measurements obtained with scanning laser polarimetry with variable corneal compensation (SLP-VCC) and optical coherence tomography (OCT). DESIGN Cross-sectional analysis of normal and glaucomatous eyes in a tertiary care academic referral practice. METHODS A commercial GDx nerve fiber analyzer was modified to enable the measurement of corneal polarization axis and magnitude so that compensation for corneal birefringence was eye specific. Complete examination, SLP with fixed corneal compensation (FCC) and variable corneal compensation (VCC), optical coherence tomography (OCT) imaging of the peripapillary RNFL, and automated achromatic perimetry were performed in all subjects. Exclusion criteria were visual acuity less than 20/40, diseases other than glaucoma, and unreliable perimetry. RESULTS Fifty-nine patients (59 eyes; 29 normal, 30 glaucomatous) were enrolled (mean age, 56.7 +/- 20.3 years, range, 20-91). All eyes with glaucoma had associated visual field loss (average mean defect, -8.4 +/- 5.8 dB). Using SLP-FCC, nine of 12 retardation parameters (75%) were significantly less in glaucomatous eyes. Using SLP-VCC, 11of 12 retardation parameters (92%) were significantly less in glaucomatous eyes. Multiple regression models constructed for each retardation parameter with visual field demonstrated that the following VCC parameters were statistically significant whereas FCC parameters were not: ellipse average (FCC, P =.28, VCC, P =.001), superior average (FCC, P =.38, VCC, P <.001), inferior average (FCC, P =.10, VCC, P =.008), average thickness (FCC, P =.30, VCC, P =.031), and superior integral (FCC, P =.43, VCC, P =.001). Similar results were obtained for multiple regression models constructed with OCT-derived RNFL thickness: ellipse average (FCC, P =.99, VCC, P =.002), superior average (FCC, P =.90, VCC, P <.001), inferior average (FCC, P =.61, VCC, P =.007), and superior integral (FCC, P =.92, VCC, P <.001). CONCLUSIONS Compared with fixed compensation, mean-based SLP parameters generated with SLP-VCC have greater correlation with visual function and RNFL thickness assessments obtained with OCT.

Correction for corneal polarization axis improves the discriminating power of scanning laser polarimetry

PURPOSE Corneal polarization axis (CPA) has been reported to affect retardation measurements obtained with scanning laser polarimetry (SLP). The purpose of this investigation was to prospectively determine whether correction for CPA improves the discriminating power of SLP for detection of mild-to-moderate glaucoma. DESIGN Cross-sectional analysis of normal and glaucomatous eyes. METHODS We constructed a noninvasive slit-lamp-mounted device incorporating two crossed linear polarizers and an optical retarder to measure the slow axis of corneal polarization. Complete ocular examination, standard automated perimetry, SLP imaging, and CPA measurements were performed on normal and glaucomatous eyes. One eye/subject was enrolled; if both eyes of a patient were eligible for the study, the right eye was selected. For each of the 13 SLP parameters, logistic regression was used to determine if including CPA in the model influenced the ability to discriminate between normal and glaucomatous eyes. RESULTS Forty-three normal eyes (average visual field mean defect, -0.53 +/- 1.4 dB) and 33 glaucomatous eyes (average visual field mean defect, -5.93 +/- 6.5 dB) were enrolled. CPA was significantly correlated with summary retardation parameters (average thickness and integral values) in normal (r = 0.72-0.83, P <.001 for all values) and glaucomatous eyes (r = 0.43-0.62, P =.013 to <.001). Including CPA in the model improved the ability to discriminate between normal and glaucomatous eyes for five retardation parameters quantifying retinal nerve fiber layer (RNFL) thickness (range of P values: 0.045-0.001). For inferior average thickness, area under the receiver operating characteristic (ROC) curve increased significantly (P =.002) from 0.70 to 0.78 after accounting for CPA; with a sensitivity set at 80% specificity improved from 33% to 72%. Correlations between visual field corrected pattern standard deviation and average thickness, ellipse average, superior average, and inferior average significantly increased (range of P values,.018-.001) after adjustment for CPA (r = -0.35 and -0.45, -0.38 and -0.47, -0.46 and -0.57, and -0.42 and -0.49, respectively). CONCLUSIONS Correction for CPA significantly increases the correlation between retinal nerve fiber layer structural damage and visual function and significantly improves the discriminating power of SLP for detection of mild-to-moderate glaucoma.

Late endophthalmitis associated with glaucoma drainage implants

OBJECTIVE To report the clinical course of a series of patients who had late endophthalmitis develop after glaucoma drainage implant (GDI) surgery. DESIGN Noncomparative, interventional, consecutive case series. PARTICIPANTS Four patients were identified with late endophthalmitis associated with Baerveldt glaucoma implants. METHODS The medical records of all patients with endophthalmitis associated with a GDI treated at the Bascom Palmer Eye Institute or University of Florida between January 1, 1987 and December 31, 1999 were retrospectively reviewed. Patients with culture-positive endophthalmitis diagnosed more than 1 month after GDI surgery were included in this series. MAIN OUTCOME MEASURES Visual acuity and intraocular pressure (IOP). RESULTS Late endophthalmitis associated with Baerveldt glaucoma implants developed 7 weeks to 2 years postoperatively. Exposure of the GDI tube was present in all cases. The implant was removed in three of four patients. Visual acuity worsened from preinfection level in two of four cases. IOP was controlled at last follow-up in all patients, although replacement of the explanted GDI was required in one patient. CONCLUSIONS Late endophthalmitis may occur after GDI surgery. Exposure of the GDI tube seems to represent a major risk factor for these infections. To prevent this potentially devastating complication, we recommend prophylactic surgical revision with a patch graft in all cases in which there is an exposed GDI tube.