Uday K. Addepalli

Effect of Spectrum Bias on the Diagnostic Accuracy of Spectral-Domain Optical Coherence Tomography in Glaucoma

PURPOSE To evaluate the influence of a control group on the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) in early glaucoma. METHODS In a diagnostic, case-control study, 119 eyes of 60 normal subjects with no findings suspicious for glaucoma (control cohort 1); 76 eyes of 41 subjects referred by general ophthalmologists as glaucoma suspects based on optic disc morphology, but found by glaucoma experts to be normal but with physiological variations in their optic nerves (control cohort 2); and 65 eyes of 46 early-glaucoma patients (cases) underwent imaging of the optic nerve head (ONH), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) by SD-OCT. RESULTS Areas under the receiver operating characteristic curves (AUC) of ONH parameters discriminating glaucomatous eyes from normal eyes of control cohort 2 were significantly lesser (P < 0.001) than those discriminating glaucomatous eyes from normal eyes of control cohort 1. AUCs of RNFL parameters discriminating glaucomatous eyes from normal eyes of control cohorts 2 and 1 were comparable. Although the AUCs of GCC thickness parameters were comparable, AUCs of GCC focal and global loss volume in control cohort 2 (0.684 and 0.671. respectively) were significantly less (P < 0.05) than in control cohort 1 (0.881 and 0.841, respectively). CONCLUSIONS The effectiveness of most SD-OCT parameters in detecting glaucoma significantly decreased when evaluated against a clinically relevant control group with suspicious-looking optic nerves compared with that against a control group consisting of normal subjects with no findings suspicious for glaucoma.

Corneal Thickness in Keratoconus: Comparing Optical, Ultrasound, and Optical Coherence Tomography Pachymetry

PURPOSE To compare the central and peripheral pachymetry measurements determined using Orbscan IIz (Bausch & Lomb, Rochester, NY), Visante optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA), and RTVue OCT (Oculus Technologies, Wynwood, WA) with ultrasound pachymetry in eyes with established keratoconus and to evaluate the agreement between them. DESIGN Evaluation of diagnostic technologies. PARTICIPANTS One hundred six eyes of 67 consecutive patients with a clinical diagnosis of keratoconus ranging in age from 12 to 40 years. METHODS Central corneal thickness (CCT) was determined by all the 4 techniques. Peripheral corneal thicknesses were determined using Orbscan IIz, Visante OCT, and RTVue at 8 points (superior, inferior, temporal, nasal, superior-temporal, inferior-temporal, superior-nasal, and inferior-nasal) all in the 5.0- to 7.0-mm arcuate zone. MAIN OUTCOME MEASURES Central and peripheral keratoconus thickness. RESULTS Ultrasound pachymetry determined significantly higher CCT values than Orbscan IIz (P<0.001), Visante (P<0.001), and RTVue (P = 0.037), with a mean ± standard deviation difference of 14±3 μm, 13±2 μm, and 5±3 μm, respectively. The mean CCT difference was minimal (1±3 μm; P = 0.69) between the Orbscan IIz and Visante. A strong correlation was found (r>0.80) between all the CCT measurement techniques. Orbscan IIz significantly overestimated the peripheral thickness compared with the rest, and the mean differences ranged between 21 and 60 μm. Mean peripheral thickness differences between RTVue and Visante OCT always remained less than 20 μm. Weak correlations and larger limits of agreement were found between the techniques in thinner and peripheral zones. CONCLUSIONS Orbscan IIz, Visante, RTVue, and ultrasound pachymetry show high correlation, although Orbscan IIz and Visante significantly underestimated CCT measurements compared with ultrasound pachymetry in keratoconus. Orbscan IIz significantly overestimated peripheral corneal thickness compared with RTVue and Visante.

Ability of different scanning protocols of spectral domain optical coherence tomography to diagnose preperimetric glaucoma.

PURPOSE To evaluate the ability of the optic nerve head (ONH), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) parameters of spectral domain optical coherence tomograph (SDOCT) in detecting preperimetric glaucoma. METHODS In a cross-sectional study, 34 preperimetric glaucoma eyes (34 patients) and 72 control eyes (72 subjects) with large physiologic optic disc cupping underwent ONH, RNFL, and GCC imaging with SDOCT. Preperimetric glaucoma was diagnosed in the presence of glaucomatous optic neuropathy on masked evaluation of optic disc photographs by two glaucoma experts and normal visual fields. The ability of SDOCT parameters to discriminate preperimetric glaucoma eyes from eyes with large physiologic cups was evaluated by areas under the receiver operating characteristic curves (AUC), sensitivities at fixed specificities, and likelihood ratios (LR). RESULTS All SDOCT parameters were significantly different (P < 0.05) between the two groups. The ONH, RNFL, and GCC parameters with best AUCs to differentiate preperimetric glaucoma from eyes with large physiologic cups were vertical cup to disc ratio (0.76), inferior quadrant RNFL thickness (0.76), and inferior quadrant GCC thickness (0.75), respectively. Sensitivities at 95% specificity of SDOCT parameters ranged between 15% and 29%. Likelihood ratios of outside normal limits category of parameters ranged between 3 and 11, and within normal limits category between 0.5 and 0.8. CONCLUSIONS Diagnostic abilities of ONH, RNFL, and GCC parameters of SDOCT to differentiate preperimetric glaucoma eyes from control eyes with large physiologic cupping were only moderate.

Effect of cataract extraction on Visual Field Index in glaucoma.

Purpose:To determine the effect of cataract on the Visual Field Index (VFI) in glaucoma patients. Methods:Reliable visual fields (VFs) of 53 patients (53 eyes) with primary glaucoma who underwent phacoemulsification either alone or combined with trabeculectomy were analyzed before and after surgery. All patients had VFs within a period of 15 months before and after surgery. VFI, mean deviation (MD), and pattern standard deviation (PSD) before surgery were compared with those after surgery. Results:Median (25th and 75th percentiles) MD after cataract surgery [−10.52 dB (range, −19.25 to −4.86 dB)] was significantly better (P=0.003) than that before surgery [−11.74 dB (range, −20.61 to −7.15 dB)]. Median PSD after surgery [4.76 dB (range, 2.48 to 9.83)] was worse (P=0.01) than that before surgery [3.50 dB (range, 1.93 to 8.20 dB)] when eyes with MD better than −20 dB were considered (41 eyes). VFI after surgery [80% (range, 44% to 94%)] was similar (P=0.92) to that before surgery [77% (range, 37% to 92%)]. MD improved while VFI remained unchanged in both nuclear sclerotic (n=41) and posterior subcapsular cataracts (n=12). Conclusions:MD and PSD were significantly affected, whereas VFI was not affected by cataract. VFI may be a more robust measure of VF damage than MD or PSD in glaucomatous eyes with coexisting cataracts.

Effect of Scan Quality on Diagnostic Accuracy of Spectral-Domain Optical Coherence Tomography in Glaucoma

PURPOSE To evaluate the effect of scan quality on the diagnostic accuracies of optic nerve head (ONH), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) parameters of spectral-domain optical coherence tomography (SD OCT) in glaucoma. DESIGN Cross-sectional study. METHODS Two hundred fifty-two eyes of 183 control subjects (mean deviation [MD]: -1.84 dB) and 207 eyes of 159 glaucoma patients (MD: -7.31 dB) underwent ONH, RNFL, and GCC scanning with SD OCT. Scan quality of SD OCT images was based on signal strength index (SSI) values. Influence of SSI on diagnostic accuracy of SD OCT was evaluated by receiver operating characteristic (ROC) regression. RESULTS Diagnostic accuracies of all SD OCT parameters were better when the SSI values were higher. This effect was statistically significant (P < .05) for ONH and RNFL but not for GCC parameters. In mild glaucoma (MD of -5 dB), area under ROC curve (AUC) for rim area, average RNFL thickness, and average GCC thickness parameters improved from 0.651, 0.678, and 0.726, respectively, at an SSI value of 30 to 0.873, 0.962, and 0.886, respectively, at an SSI of 70. AUCs of the same parameters in advanced glaucoma (MD of -15 dB) improved from 0.747, 0.890, and 0.873, respectively, at an SSI value of 30 to 0.922, 0.994, and 0.959, respectively, at an SSI of 70. CONCLUSION Diagnostic accuracies of SD OCT parameters in glaucoma were significantly influenced by the scan quality even when the SSI values were within the manufacturer-recommended limits. These results should be considered while interpreting the SD OCT scans for glaucoma.

Relationship between intraocular pressure and rate of visual field progression in treated glaucoma.

Purpose:To evaluate the relationship between intraocular pressure (IOP) and the rate of visual field (VF) progression in treated glaucoma. Methods:In a clinic-based, retrospective study, data of consecutive primary open-angle and angle-closure glaucoma patients with ≥5 VFs between 1989 and 2008 were analyzed. The Guided Progression Analysis software, which provides the rate of change of Visual Field Index per year, was used to assess the rate of progression (ROP). IOP measurements during the VF examination visits were extracted, and mean, peak, and fluctuation (SD) of IOP during the follow-up were calculated. Relationships between IOP parameters and ROP were analyzed using regression models. Other risk factors evaluated were age, sex, type of glaucoma, presence of hypertension and diabetes, severity of VF loss at presentation, glaucoma surgery during follow-up, number of antiglaucoma medications, and follow-up duration. Results:During the study period, 296 eyes of 213 glaucoma patients had undergone ≥5 VFs. IOP fluctuation was the only IOP parameter significantly associated with ROP (&bgr;=−0.37, P=0.02). Evaluated in a multivariate model with other risk factors, the severity of VF damage at presentation (&bgr;=0.08, P=0.002) and IOP fluctuation (&bgr;=−0.35, P=0.02) remained significantly associated with ROP. Greater IOP fluctuation was seen in eyes undergoing glaucoma surgery and eyes requiring more antiglaucoma medications during follow-up. Conclusions:Long-term IOP fluctuation was the most important IOP parameter associated with increased ROP of glaucomatous VF loss. This association is likely due to the confounding effect of enhanced therapy in eyes suspected to be progressing.

Spectral domain optical coherence tomography in children operated for primary congenital glaucoma

Aim To evaluate optic nerve head, retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thickness measurements in children operated for primary congenital glaucoma (PCG) using spectral domain optical coherence tomography (SDOCT). Methods In a case-control study, 45 eyes of 37 children operated for PCG and 72 eyes of 41 normal children underwent optic nerve head, RNFL and GCC imaging with SDOCT. Differences in SDOCT parameters between PCG and control group, correlation between SDOCT parameters and a range of clinical variables, namely preop corneal diameter, intraocular pressure, degree of corneal oedema and age at which surgery was performed in PCG eyes, were evaluated. Results Mean (±SD) age of children in PCG group was 10.1±3.6 years and control group was 13.6±3.2 years (p<0.001) at the time of SDOCT imaging. Visual fields, whenever possible were unreliable in 20 of 23 PCG and 30 of 46 normal eyes. All SDOCT parameters were significantly different (p<0.001) in PCG compared with control group. All global SDOCT parameters (rim area, average RNFL and GCC thickness) correlated significantly with the clinical cup to disc ratio measurements (correlation coefficients better than −0.70) in children with PCG. Age at which surgery was performed was inversely related to SDOCT parameter thickness but was not statistically significant. Conclusions All SDOCT parameters were significantly different in children operated for PCG compared with normal children. Future research should evaluate the test-retest variability of SDOCT and its ability to diagnose progression in children unable to perform reliable visual field tests.

Glaucoma in microspherophakia: presenting features and treatment outcomes.

Purpose:To report the clinical features, management, and treatment outcomes of glaucoma in microspherophakia. Methods:Medical records of 159 eyes of 80 subjects with microspherophakia were reviewed. The clinical features at presentation, presence of glaucoma, methods of treatment, and their outcomes were noted. Glaucoma was diagnosed based on intraocular pressure (IOP)≥22 mm Hg on 2 different occasions and/or glaucomatous optic disc damage. Angle closure was defined as occludable angles >270 degrees with or without presence of peripheral anterior synechiae. Results:Glaucoma was diagnosed in 81 eyes (51%). The mean age of subjects was 20±13 years, mean refractive error was −13.5±5.5, the mean IOP was 27.7±11.1 mm Hg. IOP≥22 mm Hg was present in 84% of eyes, disc damage in 59% of the eyes, 75% eyes had angle closure, and 25% had open angle on gonioscopy. Subluxation of crystalline lens was seen in 53 eyes and 14 eyes had dislocation of the lens; systemic associations were present in 21 subjects (3 Marfan syndrome, 18 Weill-Marchesani syndrome). Nine eyes out of 51 and 2 out of 16 eyes responded to medical treatment and laser iridotomy, respectively. Of the 48 eyes that required surgical intervention, 24 eyes underwent trabeculectomy. Complete success probability of trabeculectomy was 86% [95% confidence interval (CI), 63%-95%] at 6 months, 77% (95% CI, 53%-90%) at 1 year, which was maintained till 7 years, and reduced to 61% (95%CI, 26%-84%) at 8 years. Nearly 20% of eyes at presentation and 30% of the eyes at last follow-up were blind due to glaucoma. Conclusions:More than half of the eyes with microspherophakia in this series presented with glaucoma; angle closure was the predominant form of glaucoma. Blindness due to glaucoma in microspherophakia was 20% to 30%.

Role of Visual Field Reliability Indices in Ruling Out Glaucoma

IMPORTANCE Standard automated perimetry is the current criterion standard for assessment of visual field (VF) loss in glaucoma. The 3 commonly used reliability indices to judge the quality of standard automated perimetry results are fixation losses (FLs) and false-positive (FP) and false-negative (FN) response rates. However, the influence of reliability indices, when within the manufacturer-recommended limits, on VF classification has been sparsely studied. OBJECTIVE To evaluate the role of VF reliability indices in ruling out glaucoma. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study of 291 eyes of 291 participants referred to a tertiary eye care facility by general ophthalmologists. The participants were suspected to have glaucoma based on optic disc appearance, but the eyes were judged to be normal with physiological cupping by glaucoma experts on masked evaluation of optic disc photographs. All participants underwent VF testing with the Swedish interactive threshold algorithm standard 24-2 program. MAIN OUTCOMES AND MEASURES Logistic regression models were used to evaluate the associations between reliability indices and FP classifications on VF testing (glaucoma hemifield test as outside normal limits and pattern standard deviation with P < .05). RESULTS Median FL, FP, and FN response rates were 7%, 1%, and 2%, respectively. Among the 241 participants with reliable VF results (FL <20% and FP response rate <15%), the VF classification was normal in 188 (78.0%) and glaucoma (FP) in 53 (22.0%). Probability of FP VF classification was associated with FN response rates (odds ratio [OR], 1.36; 95% CI, 1.25-1.48, P < .001) but did not appear to be associated with FLs (OR, 0.96; 95% CI, 0.90-1.03, P = .30) or FP response rates (OR, 0.96; 95% CI, 0.83-1.12, P = .64). Predicted probability of FP VF classification was 9% (95% CI, 6%-14%), 40% (32%-49%), and 82% (68%-91%) at FN response rates of 0%, 8%, and 16%, respectively. CONCLUSIONS AND RELEVANCE This study suggests that FN response rates have an effect on the ability of automated VF assessments to rule out glaucoma. Since FN response rates are ignored by the manufacturer while flagging a test as unreliable, clinicians and researchers may benefit by realizing that FN response rates can lead to FP VF classification, even when their frequencies are small.

Peripapillary Retinal Nerve Fiber Layer Assessment of Spectral Domain Optical Coherence Tomography and Scanning Laser Polarimetry to Diagnose Preperimetric Glaucoma

Purpose To compare the abilities of peripapillary retinal nerve fiber layer (RNFL) parameters of spectral domain optical coherence tomograph (SDOCT) and scanning laser polarimeter (GDx enhanced corneal compensation; ECC) in detecting preperimetric glaucoma. Methods In a cross-sectional study, 35 preperimetric glaucoma eyes (32 subjects) and 94 control eyes (74 subjects) underwent digital optic disc photography and RNFL imaging with SDOCT and GDx ECC. Ability of RNFL parameters of SDOCT and GDx ECC to discriminate preperimetric glaucoma eyes from control eyes was compared using area under receiver operating characteristic curves (AUC), sensitivities at fixed specificities and likelihood ratios (LR). Results AUC of the global average RNFL thickness of SDOCT (0.786) was significantly greater (p<0.001) than that of GDx ECC (0.627). Sensitivities at 95% specificity of the corresponding parameters were 20% and 8.6% respectively. AUCs of the inferior, superior and temporal quadrant RNFL thickness parameters of SDOCT were also significantly (p<0.05) greater than the respective RNFL parameters of GDx ECC. LRs of outside normal limits category of SDOCT parameters ranged between 3.3 and 4.0 while the same of GDx ECC parameters ranged between 1.2 and 2.1. LRs of within normal limits category of SDOCT parameters ranged between 0.4 and 0.7 while the same of GDx ECC parameters ranged between 0.7 and 1.0. Conclusions Abilities of the RNFL parameters of SDOCT and GDx ECC to diagnose preperimetric glaucoma were only moderate. Diagnostic abilities of the RNFL parameters of SDOCT were significantly better than that of GDx ECC in preperimetric glaucoma.