Shaban Demirel

A method to estimate the amount of neuroretinal rim tissue in glaucoma: comparison with current methods for measuring rim area.

PURPOSE To test whether the minimum rim area assessed by spectral domain optical coherence tomography (SD-OCT), based on the shortest distance from the Bruch membrane opening (BMO) to the inner limiting membrane, corresponds more closely to retinal nerve fiber layer (RNFL) thickness and visual field mean deviation (MD) than current rim measures in early glaucoma. DESIGN Prospective cross-sectional study. METHODS We studied 221 participants with non-endstage glaucoma or high-risk ocular hypertension and performed standard automated perimetry. We received SD-OCT and confocal scanning laser ophthalmoscopy (CSLO) scans on the same day. Rim area measured by CSLO was compared with 3 SD-OCT rim measures from radial B-scans: horizontal rim area between BMO and inner limiting membrane within the BMO plane; mean minimum rim width (BMO-MRW); and minimum rim area (BMO-MRA) optimized within sectors and then summed. Correlations between these measures and either MD from perimetry or RNFL thickness from SD-OCT were compared using the Steiger test. RESULTS RNFL thickness was better correlated with BMO-MRA (r = 0.676) or BMO-MRW (r = 0.680) than with either CSLO rim area (r = 0.330, P < 0.001) or horizontal rim area (r = 0.482, P < 0.001). MD was better correlated with BMO-MRA (r = 0.534) or BMO-MRW (r = 0.546) than with either CSLO rim area (r = 0.321, P < 0.001) or horizontal rim area (0.403, P < 0.001). The correlation between MD and RNFL thickness was r = 0.646. CONCLUSIONS Minimum rim measurements from SD-OCT are significantly better correlated to both RNFL thickness and MD than rim measurements within the BMO plane or based on the clinical disc margin. They provide new structural parameters for both diagnostic and research purposes in glaucoma.

Anterior Lamina Cribrosa Surface Depth, Age, and Visual Field Sensitivity in the Portland Progression Project

PURPOSE To assess the effect of age on spectral-domain optical coherence tomography (SDOCT)-detected lamina cribrosa depth while controlling for visual field (VF) status and retinal nerve fiber layer thickness (RNFLT) in 221 high-risk ocular hypertension and glaucoma patients enrolled in the Portland Progression Project. METHODS In this cross-sectional study, each participant underwent 870-nm SDOCT to obtain high-resolution radial B-scans centered on the optic nerve head (ONH) and a standardized ophthalmologic examination, including automated perimetry, on the same day. For each ONH, an anterior lamina cribrosa surface depth (ALCSD) parameter was generated as the average perpendicular distance from each anterior lamina cribrosa surface point relative to Bruchs membrane opening (BMO) reference plane within all 24 delineated B-scans. The relative effects of age, age-corrected VF status (mean deviation [MD]), and RNFLT on ALCSD were analyzed. RESULTS The mean age ± SD of participants was 64 ± 11 years (range, 33-90 years). The relationship between ALCSD and MD was age-dependent. ALCSD = 407.68 - 67.13 × MD - 0.08 × Age + 0.89 × MD × Age (MD, P = 0.001; MD × Age, P = 0.004). The relationship between ALCSD and RNFLT may also be age-dependent but did not achieve significance (interaction term, P = 0.067). ALCSD increased with worse VF status in younger eyes but not in older eyes. In older eyes, the anterior lamina was shallower than in younger eyes for the same VF status and RNFLT. CONCLUSIONS These data are consistent with the concept that structure/structure and structure/function relationships change with age.

Assessment of the Reliability of Standard Automated Perimetry in Regions of Glaucomatous Damage

PURPOSE Visual field testing uses high-contrast stimuli in areas of severe visual field loss. However, retinal ganglion cells saturate with high-contrast stimuli, suggesting that the probability of detecting perimetric stimuli may not increase indefinitely as contrast increases. Driven by this concept, this study examines the lower limit of perimetric sensitivity for reliable testing by standard automated perimetry. DESIGN Evaluation of a diagnostic test. PARTICIPANTS A total of 34 participants with moderate to severe glaucoma; mean deviation at their last clinic visit averaged -10.90 dB (range, -20.94 to -3.38 dB). A total of 75 of the 136 locations tested had a perimetric sensitivity of ≤ 19 dB. METHODS Frequency-of-seeing curves were constructed at 4 nonadjacent visual field locations by the Method of Constant Stimuli (MOCS), using 35 stimulus presentations at each of 7 contrasts. Locations were chosen a priori and included at least 2 with glaucomatous damage but a sensitivity of ≥ 6 dB. Cumulative Gaussian curves were fit to the data, first assuming a 5% false-negative rate and subsequently allowing the asymptotic maximum response probability to be a free parameter. MAIN OUTCOME MEASURES The strength of the relation (R(2)) between perimetric sensitivity (mean of last 2 clinic visits) and MOCS sensitivity (from the experiment) for all locations with perimetric sensitivity within ± 4 dB of each selected value, at 0.5 dB intervals. RESULTS Bins centered at sensitivities ≥ 19 dB always had R(2) >0.1. All bins centered at sensitivities ≤ 15 dB had R(2) <0.1, an indication that sensitivities are unreliable. No consistent conclusions could be drawn between 15 and 19 dB. At 57 of the 81 locations with perimetric sensitivity <19 dB, including 49 of the 63 locations ≤ 15 dB, the fitted asymptotic maximum response probability was <80%, consistent with the hypothesis of response saturation. At 29 of these locations the asymptotic maximum was <50%, and so contrast sensitivity (50% response rate) is undefined. CONCLUSIONS Clinical visual field testing may be unreliable when visual field locations have sensitivity below approximately 15 to 19 dB because of a reduction in the asymptotic maximum response probability. Researchers and clinicians may have difficulty detecting worsening sensitivity in these visual field locations, and this difficulty may occur commonly in patients with glaucoma with moderate to severe glaucomatous visual field loss.

Bruch's Membrane Opening Minimum Rim Width and Retinal Nerve Fiber Layer Thickness in a Normal White Population: A Multicenter Study

PURPOSE Conventional optic disc margin-based neuroretinal rim measurements lack a solid anatomic and geometrical basis. An optical coherence tomography (OCT) index, Bruchs membrane opening minimum rim width (BMO-MRW), addresses these deficiencies and has higher diagnostic accuracy for glaucoma. We characterized BMO-MRW and peripapillary retinal nerve fiber layer thickness (RNFLT) in a normal population. DESIGN Multicenter cross-sectional study. PARTICIPANTS Normal white subjects. METHODS An approximately equal number of subjects in each decade group (20-90 years of age) was enrolled in 5 centers. Subjects had normal ocular and visual field examination results. We obtained OCT images of the optic nerve head (24 radial scans) and peripapillary retina (1 circular scan). The angle between the fovea and BMO center (FoBMO angle), relative to the horizontal axis of the image frame, was first determined and all scans were acquired and analyzed relative to this eye-specific FoBMO axis. Variation in BMO-MRW and RNFLT was analyzed with respect to age, sector, and BMO shape. MAIN OUTCOME MEASURES Age-related decline and between-subject variability in BMO-MRW and RNFLT. RESULTS There were 246 eyes of 246 subjects with a median age of 52.9 years (range, 19.8-87.3 years). The median FoBMO angle was -6.7° (range, 2.5° to -17.5°). The BMO was predominantly vertically oval with a median area of 1.74 mm(2) (range, 1.05-3.40 mm(2)). Neither FoBMO angle nor BMO area was associated with age or axial length. Both global mean BMO-MRW and RNFLT declined with age at a rate of -1.34 μm/year and -0.21 μm/year, equivalent to 4.0% and 2.1% loss per decade of life, respectively. Sectorially, the most rapid decrease occurred inferiorly and the least temporally; however, the age association was always stronger with BMO-MRW than with RNFLT. There was a modest relationship between mean global BMO-MRW and RNFLT (r = 0.35), whereas sectorially the relationship ranged from moderate (r = 0.45, inferotemporal) to nonexistent (r = 0.01, temporal). CONCLUSIONS There was significant age-related loss of BMO-MRW in healthy subjects and notable differences between BMO-MRW and RNFLT in their relationship with age and between each other. Adjusting BMO-MRW and RNFLT for age and sector is important in ensuring optimal diagnostics for glaucoma.

Incidence and prevalence of short wavelength automated perimetry deficits in ocular hypertensive patients

PURPOSE To determine the prevalence and incidence of short wavelength automated perimetry deficits in comparison to standard automated perimetry deficits in patients with ocular hypertension. METHODS Five hundred eyes of 250 patients with ocular hypertension were recruited into a prospective, longitudinal study and tested with standard automated perimetry and short wavelength automated perimetry annually for 5 years. Both eyes of 60 normal subjects, 21 to 85 years of age, were used to establish normative data for short wavelength automated perimetry and standard automated perimetry. This allowed independent evaluation of left and right eyes of patients. All normal data were corrected for age, and short wavelength automated perimetry results were corrected for lens transmission. The lowest fifth and first percentiles for the normal observers were derived for the 10 glaucoma hemifield test zones for short wavelength automated perimetry and standard automated perimetry. Visual fields were considered outside normal limits if two glaucoma hemifield test zones were below the normal fifth percentile or one glaucoma hemifield test zone was below the normal first percentile. RESULTS Baseline prevalence of short wavelength automated perimetry and standard automated perimetry deficits were 9.4% and 1.4%, respectively. During the study, incident rates of field loss were 6.2% (1.23% per year) for short wavelength automated perimetry and 5.9% (1.18% per year) for standard automated perimetry. Once abnormal, 80% of short wavelength automated perimetry fields remained abnormal on the next examination, whereas only 45% of abnormal standard automated perimetry fields remained abnormal. New short wavelength automated perimetry deficits in ocular hypertensives were more prominent and more persistent than new standard automated perimetry deficits. CONCLUSIONS Our findings are consistent with the interpretation that short wavelength automated perimetry deficits occur before standard automated perimetry deficits in glaucoma. The similar incidence rates suggest that both standard automated perimetry and short wavelength automated perimetry are monitoring the same underlying glaucomatous disease process.

Long-term Comparative Effectiveness of Telemedicine in Providing Diabetic Retinopathy Screening Examinations A Randomized Clinical Trial

IMPORTANCE Minimal information exists regarding the long-term comparative effectiveness of telemedicine to provide diabetic retinopathy screening examinations. OBJECTIVE To compare telemedicine to traditional eye examinations in their ability to provide diabetic retinopathy screening examinations. DESIGN, SETTING, AND PARTICIPANTS From August 1, 2006, through September 31, 2009, 567 participants with diabetes were randomized and followed up to 5 years of follow-up (last date of patient follow-up occurred on August 6, 2012) as part of a multicenter randomized clinical trial with an intent to treat analysis. We assigned participants to telemedicine with a nonmydriatic camera in a primary care medical clinic (n = 296) or traditional surveillance with an eye care professional (n = 271). Two years after enrollment, we offered telemedicine to all participants. MAIN OUTCOMES AND MEASURES Percentage of participants receiving annual diabetic retinopathy screening examinations, percentage of eyes with worsening diabetic retinopathy during the follow-up period using a validated scale from stage 0 (none) to stage 4 (proliferative diabetic retinopathy), and percentage of telemedicine participants who would require referral to an eye care professional for follow-up care using a cutoff of moderate diabetic retinopathy or worse, the presence of macular edema, or an unable-to-determine result for retinopathy or macular edema. RESULTS The telemedicine group was more likely to receive a diabetic retinopathy screening examination when compared with the traditional surveillance group during the 6-month or less (94.6% [280/296] vs 43.9% [119/271]; 95% CI, 46.6%-54.8%; P < .001) and greater than 6-month through 18-month (53.0% [157/296] vs 33.2% [90/271]; 95% CI, 16.5%-23.1%; P < .001) time bins. After we offered telemedicine to both groups, we could not identify a difference between the groups in the percentage of diabetic retinopathy screening examinations. Diabetic retinopathy worsened by 2 stages or more in 35 (8.6%) of 409 participants (95% CI, 5.8%-11.2%) and improved by 2 stages or more in 5 (1.2%) of 409 participants (95% CI, 0.1%-2.3%) during the 4-year period. The percent of telemedicine participants requiring referral ranged from 19.2% (52/271) to 27.9% (58/208). CONCLUSIONS AND RELEVANCE Telemedicine increased the percentage of diabetic retinopathy screening examinations, most participants did not require referral to an eye care professional, and diabetic retinopathy levels were generally stable during the study period. This finding suggests that primary care clinics can use telemedicine to screen for diabetic retinopathy and monitor for disease worsening over a long period. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01364129.

Anatomic vs. acquired image frame discordance in spectral domain optical coherence tomography minimum rim measurements.

Purpose To quantify the effects of using the fovea to Bruchs membrane opening (FoBMO) axis as the nasal-temporal midline for 30° sectoral (clock-hour) spectral domain optical coherence tomography (SDOCT) optic nerve head (ONH) minimum rim width (MRW) and area (MRA) calculations. Methods The internal limiting membrane and BMO were delineated within 24 radial ONH B-scans in 222 eyes of 222 participants with ocular hypertension and glaucoma. For each eye the fovea was marked within the infrared reflectance image, the FoBMO angle (θ) relative to the acquired image frame (AIF) horizontal was calculated, the ONH was divided into 30°sectors using a FoBMO or AIF nasal/temporal axis, and SDOCT MRW and MRA were quantified within each FoBMO vs. AIF sector. For each sector, focal rim loss was calculated as the MRW and MRA gradients (i.e. the difference between the value for that sector and the one clockwise to it divided by 30°). Sectoral FoBMO vs. AIF discordance was calculated as the difference between the FoBMO and AIF values for each sector. Generalized estimating equations were used to predict the eyes and sectors of maximum FoBMO vs. AIF discordance. Results The mean FoBMO angle was −6.6±4.2° (range: −17° to +7°). FoBMO vs. AIF discordance in sectoral mean MRW and MRA was significant for 7 of 12 and 6 of 12 sectors, respectively (p<0.05, Wilcoxon test, Bonferroni correction). Eye-specific, FoBMO vs. AIF sectoral discordance was predicted by sectoral rim gradient (p<0.001) and FoBMO angle (p<0.001) and achieved maximum values of 83% for MRW and 101% for MRA. Conclusions Using the FoBMO axis as the nasal-temporal axis to regionalize the ONH rather than a line parallel to the AIF horizontal axis significantly influences clock-hour SDOCT rim values. This effect is greatest in eyes with large FoBMO angles and sectors with focal rim loss.

Factors Predicting the Rate of Functional Progression in Early and Suspected Glaucoma

PURPOSE Clinical trials in glaucoma have often sought to predict whether a patient will progress or remain stable. This study proposes to combine and support results from earlier studies, forming a model to predict the actual rate of functional change in glaucoma. METHODS Data were taken from 259 eyes of 150 participants with early or suspected glaucoma in the ongoing Portland Progression Project. A total of 3854 study visits were available, each consisting of visual acuity, confocal scanning laser ophthalmoscopy (CSLO), and perimetry. The rate of functional change was calculated over each of 1541 series of six consecutive visits. Mixed effects models were formed to predict these rates using baseline perimetric measurements and CSLO parameters, together with IOP, age, and change in visual acuity through the series (to remove any confound from media changes). RESULTS Cup volume from CSLO was predictive of subsequent rate of functional change (P = 0.036), together with baseline mean deviation (P < 0.001) and pattern standard deviation (P = 0.097), age (P = 0.013), maximum IOP during the sequence (P = 0.004), and change in acuity during the sequence (P = 0.022). In a similar model, rim area was less predictive of functional change (P = 0.066). CONCLUSIONS A larger optic cup and/or a more damaged visual field are predictive of more rapid perimetric sensitivity loss. The structural parameters most closely correlated with current functional status may not be the parameters that are most useful for predicting the future course of a patients disease. Maximum IOP may be a more important risk factor than mean IOP over the same time period.

Effect of Treatment on the Rate of Visual Field Change in the Ocular Hypertension Treatment Study Observation Group

PURPOSE The goal in this study was to compare rates of visual field (VF) change before and after the initiation of treatment in participants originally randomized to the observation arm of the Ocular Hypertension Treatment Study (OHTS). METHODS We included OHTS participants originally randomized to observation and excluded those who reached non-POAG endpoints. VF progression was determined using trend analysis. Global and localized rates of VF change were calculated based on linear regression over time of mean deviation (MD) and threshold sensitivity values for each test location. MD rates (MDR) and pointwise linear regression (PLR) analysis were also assessed using six VF tests before and after the initiation of treatment. A PLR endpoint was defined as a VF test location progressing faster than -0.5 dB/year at P < 0.01. RESULTS We included 780 eyes from 432 OHTS participants. Following the initiation of treatment, the mean MDR decreased from -0.23 ± 0.6 to -0.06 ± 0.5 dB/year (P < 0.01) and the number of VF locations reaching a PLR endpoint decreased from 2.13 ± 6.0 to 1.00 ± 4.0 (P < 0.01). The benefit of treatment was significant both among participants who did not convert (-0.17 ± 0.6 vs. -0.01 ± 0.5 dB/year, P < 0.01) and among those who converted to glaucoma (-0.51 ± 0.8 vs. -0.27 ± 0.7 dB/year, P < 0.01) based on the OHTS event-based endpoint. CONCLUSIONS The initiation of ocular hypotensive medication among OHTS participants originally randomized to observation significantly reduced the velocity of VF progression.

Is There Evidence for Continued Learning Over Multiple Years in Perimetry

Purpose. The existence of learning effects in perimetry, whereby a subjects first test is more variable and has lower mean sensitivity (MS) than subsequent tests, is well established. However, studies have typically examined this issue by testing subjects at a frequency that would be unusual in a clinical setting. This study seeks to determine the validity of these conclusions for less frequent, yet more clinically realistic, testing rates. Methods. One hundred sixty eyes of 80 subjects with suspected or early glaucoma were included. Subjects were tested annually for 8 years using white-on-white standard automated perimetry (SAP) and short wavelength automated perimetry (SWAP). All subjects had undergone at least one test with both paradigms before entering the study. Results. For SAP, MS increased by 0.5 dB over the first year, and then showed no significant change until after year 5 (despite expected effects of aging and disease progression), after which it started to decline. For SWAP, MS of the average eye continued to improve until year 6 of the study. Conclusions. Our findings seem to indicate a prolonged learning effect for SWAP, with MS increasing for several years. A smaller prolonged learning effect may also be present for SAP, counteracting the effects of aging and disease progression. Deterioration of the subjects visual field may be underestimated within this period.