Deep Optic Nerve Head Morphology in Tilted Disc Syndrome and Its Clinical Implication on Visual Damage

Ability of Cirrus High-Definition Spectral-Domain Optical Coherence Tomography Clock-Hour, Deviation, and Thickness Maps in Detecting Photographic Retinal Nerve Fiber Layer Abnormalities

Eyes with initial bihemifield defects show faster progression compared with eyes with initial single-hemifield involvement, suggesting greater optic nerve susceptibility to glaucomatous damage. We hypothesized that certain disc phenotypes may exist in patients with glaucoma who have bihemispheric structural damage at the initial stage of the disease. To identify the optic disc characteristics related to bihemispheric retinal nerve fiber layer (RNFL) defects in early-stage glaucoma. A cross-sectional study of 136 patients with early-stage primary open-angle glaucoma from a glaucoma referral practice. Eyes were divided into those with RNFL defects in the superior or the inferior hemisphere (group 1) and those with bihemispheric RNFL defects (group 2). We measured the degree of horizontal tilt angle and RNFL thickness using spectral-domain optical coherence tomography. We performed multivariate logistic regression analysis to determine potential risk factors related to the bihemispheric RNFL defects. Bihemispheric RNFL defects. Disc ovality (defined as the ratio between the longest and shortest diameters of the optic disc), the degree of horizontal tilt angle, and the presence of bihemispheric RNFL defects. Asymmetry in RNFL thickness between hemispheres was defined as the difference between the superior and inferior mean RNFL thickness. Disc ovality (mean [SD], 1.09 [0.12] in group 1 vs 1.18 [0.18] in group 2; difference, -0.09; 95% CI, -0.14 to -0.03), proportion of tilted discs (5.3% vs 17.5%, respectively; difference, -12.2; 95% CI, -13.0 to -11.4), and horizontal tilt angle (mean [SD], 4.17° [4.13°] vs 5.93° [4.84°], respectively; difference, -1.76; 95% CI, -3.47 to -0.03) were significantly different between groups 1 and 2 (P = .001, P = .03, and P = .045, respectively). The asymmetry in RNFL thickness decreased with increased disc ovality (exponentiation of the B coefficient, 1.67; 95% CI, 1.10-2.55; P = .02), although associations were not identified with spherical equivalent, axial length, or the angle between the temporal retinal veins. In multivariate logistic analysis, disc ovality was suggested to be an independent risk factor for bihemispheric RNFL defects, after controlling for mean deviation, age, axial length, and disc area (P = .02). Optic disc tilt appears to be associated with bihemispheric RNFL defects in patients with early glaucoma, regardless of their refractive status. These data suggest that disc tilt, associated with bihemispheric structural damages, is a risk factor for glaucoma progression.

BackgroundWe investigated the association between metabolic syndrome and localized retinal nerve fiber layer (RNFL) defects in nonglaucomatous subjects.MethodsWe examined 20,385 adults who visited the Health Promotion Center of Seoul St. Mary’s Hospital between May 2015 and April 2016. After excluding those with known glaucoma or glaucomatous optic discs, subjects with and without localized RNFL defects were 1:5 propensity score matched. Metabolic syndrome components, including central obesity, elevated triglyceride, reduced high-density lipoprotein (HDL) cholesterol, elevated blood pressure (BP), and elevated fasting glucose, were compared between two groups. We performed logistic regression to investigate the association between RNFL defects and each component of metabolic syndrome and the number of metabolic syndrome components.ResultsSubjects with RNFL defects showed higher waist-to-hip ratios, systolic BP (SBP) and diastolic BP (DBP), fasting blood glucose, and hemoglobin A1c (HbA1c) levels than did those without RNFL defects both before and after propensity score matching. The number of metabolic syndrome components was significantly greater in those with RNFL defects (1.66±1.35) than in those without (1.27±1.32, P<0.01). In multivariate logistic regression, the odds ratio (OR) of RNFL defects was significantly increased in subjects with central obesity [OR =1.53, 95% confidence interval (CI): 1.11–2.13], elevated BP (OR =1.50, 95% CI: 1.09–2.05), and an elevated fasting glucose level (OR =1.42, 95% CI: 1.03–1.97). An increased number of metabolic syndrome components was associated with a higher risk of RNFL defects.ConclusionsLocalized RNFL defects in nonglaucomatous subjects are associated with metabolic syndrome components, including central obesity, elevated BP, and an elevated fasting glucose level, suggesting that comorbid metabolic syndrome should be considered when evaluating subjects with RNFL defects.

Aims/Purpose: To investigate the association between metabolic syndrome and localized retinal nerve fibre layer (RNFL) defects in nonglaucomatous subjects.Methods: We examined 20 385 adults at the Health Promotion Center in Seoul St. Mary's Hospital between May 2015 and April 2016. Subjects with and without localized RNFL defects were 1:5 propensity score matched. Metabolic syndrome components, central obesity, elevated triglyceride, reduced HDL cholesterol, elevated blood pressure and elevated fasting glucose, were compared between two groups. Logistic regression was performed to investigate the association between RNFL defects and each metabolic syndrome component as well as the number of metabolic syndrome components.Results: Subjects with RNFL defects showed higher waist to hip ratio, systolic and diastolic BP, fasting blood glucose and HbA1c compared to those without RNFL defects before and after propensity score matching. The number of metabolic syndrome components was significantly greater in those with RNFL defects (1.66 ± 1.35) compared to those without (1.27 ± 1.32, p &lt; 0.01). In multivariate logistic regression, the odds of RNFL defects were significantly increased in subjects with central obesity (OR = 1.53, 95% confidence interval [CI] = 1.11–2.13), elevated blood pressure (OR = 1.50, 95% CI = 1.09–2.05), and elevated fasting glucose (OR = 1.42, 95% CI = 1.03–1.97). Greater number of metabolic syndrome components was associated with higher odds of RNFL defects.Conclusions: The presence of localized RNFL defects in nonglaucomatous subjects is associated with metabolic syndrome components, including central obesity, elevated BP and elevated fasting glucose, suggesting that comorbid metabolic syndromes should be considered when evaluating subjects with RNFL defects.

To investigate the characteristics of retinal nerve fiber layer (RNFL) defects associated with type II diabetes. Forty nonglaucomatous eyes with type II diabetes and 54 eyes with early open angle glaucoma that exhibited a localized RNFL defect and 42 eyes from age- and sex-matched nondiabetic, nonglaucomatous controls were imaged with red-free fundus photography and optical coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec). The area under the receiver operating characteristic curves of eyes with diabetes was compared with that of eyes with glaucoma. When an RNFL defect on fundus photographs was identified in the quadrant, clock-hour, temporal-superior-nasal-inferior-temporal (TSNIT), deviation, and thickness maps, it was considered a true detection. In eyes with diabetes, the RNFL defects were located more frequently in the superior hemisphere than they were in those with glaucoma (P < 0.001). The angular locations of RNFL defects in eyes with diabetes (56.1 ± 12.7°) were significantly farther from the fovea compared with those in glaucoma (44.3 ± 17.3°; P < 0.001); in addition, the width of RNFL defects in diabetes (5.1 ± 2.3°) was significantly narrower than those in glaucoma (20.8 ± 12.3°; P < 0.001). The best parameter discriminating RNFL defects in diabetes from those in glaucoma was width of RNFL defect (0.955), followed by rim area (0.844), and average RNFL (0.791). The thickness map showed a sensitivity (70%) and specificity (69.1%), superior to those of all other maps in eyes with diabetes. The narrow width and identification of RNFL defect in thickness map obtained with Cirrus HD-OCT seems to be an effective tool for detecting RNFL defects in diabetes.

To evaluate the efficacy of a new automatic computer-aided detection (CAD) system for mass screening of retinal nerve fibre layer (RNFL) defects in a large population using fundus photographs. Among the fundus photographs of 1200 consecutive subjects who visited a healthcare centre, a total of 2270 photographs appropriate for analysis were tested. The photographs were first reviewed by two expert ophthalmologists for detection of RNFL defects (gold standard manual detection). The images were then analysed using an automatic CAD system for detecting RNFL defects in various cases of glaucomatous and non-glaucomatous optic neuropathy. A free-response receiver operating characteristics curve was generated to evaluate the validity of the CAD system. The results of the automatic detection were compared with those of manual detection, and sensitivity and specificity of the CAD system were calculated. In manual detection of 2270 photographs, 41 RNFL defects from 36 photographs (1.6%) were detected, and no RNFL defects were found in 2234 photographs (98.4%). The sensitivity of the CAD system for detecting RNFL defects was 90.2% (37/41 RNFL defects) and the specificity was 72.5% (1620/2234 photographs with no RNFL defects) at a false-positive rate of 0.36 per image. The new CAD system successfully detected RNFL defects during mass screening of fundus photographs in a large population who visited a healthcare centre. The proposed algorithm can be useful for clinicians in screening RNFL defects in healthcare centres. The false-positive rate is still unsatisfactory, although improved compared with the previous study. Further studies are needed to enhance the speed and specificity of image analysis using the CAD system.

To investigate the influence of angular width and peripapillary position of localized retinal nerve fiber layer (RNFL) defects on their detection by the time-domain optical coherence tomography (OCT). Fast RNFL Stratus OCT scans were obtained from 186 eyes of 186 newly detected glaucoma patients with only a single, localized RNFL defect in either eye. The RNFL defects were divided into subgroups according to their angular width at 15° intervals and superior or inferior position. In the sector average graph of OCT results, abnormal clock-hour sectors were evaluated at P < 5%. Among 154 eyes included in the final data analysis, mean angular width of localized RNFL defects was 21.82 ± 10.38°, and 108 eyes (70.1%) had an inferiorly located RNFL defect. Localized RNFL defects with an angular width interval of 30° to 45° were more frequently detected by Stratus OCT than those with an angular width of <15° (odds ratio = 30.32, P = 0.001). Inferior RNFL defects were not detected more frequently by Stratus OCT than superior RNFL defects (odds ratio = 1.58, P = 0.24). Only the angular width of localized RNFL defects had a significant influence on the sensitivity of the time-domain OCT.

To evaluate the ability of Stratus optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA) with its internal normative database to discriminate between healthy eyes and eyes with a localized retinal nerve fiber layer (RNFL) defect not accompanied by a perimetric defect according to standard automated perimetry (SAP) (i.e., a preperimetric localized RNFL defect). Data were retrospectively reviewed from 49 eyes of 49 subjects with preperimetric localized RNFL defects, and 49 healthy control eyes of 49 age-matched subjects, with classification into each group based primarily on red-free fundus photography The sensitivity and specificity of various OCT RNFL thickness parameters for identifying subjects with preperimetric localized RNFL defects was determined. In addition, the topographic relationship between the OCT-measured RNFL thickness and the localized RNFL defect location according to red-free fundus photography (i.e., the red-free RNFL defect) was examined. results. The sensitivity of the Stratus OCT RNFL thickness parameters ranged from 2.0% to 40.8%. The highest sensitivity was yielded using a criterion of > or =1 clock hour that were abnormal at the 5% level, which had a specificity of 85.7%. The OCT-measured RNFL thickness showed excellent topographic agreement with the red-free RNFL defect location. Although the sensitivity of current Stratus OCT RNFL thickness parameters is low for preperimetric localized RNFL defects, it appears that OCT has the potential to recognize such defects. Further study is needed to develop new analytical methods that will increase OCT sensitivity for identifying preperimetric localized RNFL damage.

This study demonstrated the high topographic correlation between the red-free fundus photographs and en face structural images in eyes with glaucomatous progression. The purpose of this study was to compare the progression of localized retinal nerve fiber layer (RNFL) defects in red-free fundus photographs, en face structural images, and optical coherence tomography angiography (OCTA) images. We performed a retrospective, comparative study on 45 glaucomatous eyes showing RNFL defect widening in red-free photography. The localized RNFL defect in the red-free photographs was termed as red-free defect. The wedge-shaped hyporeflective area radiating from the optic nerve head in the optical coherence tomography (OCT) en face structural images and OCTA images was defined as en face defect and OCTA defect, respectively. The baseline and follow-up angular parameters of each red-free defect were compared with those of en face defect and OCTA defect. When the baseline angular parameters were compared, there were no significant differences between red-free defect and en face defect, and between red-free defect and OCTA defect (all, P>0.017). In addition, the follow-up angular parameters showed no difference between red-free defect and en face defect. However, the OCTA defect showed significantly greater values compared with red-free defect and en face defect with respect to the distal angular location and angular width at follow-up visit (36.78±15.10 vs. 34.10±15.09 vs. 33.40±15.05 degrees, both, P<0.001). Localized RNFL defects detected in red-free photographs showed high topographic correlation with defects detected in OCT en face structural images, and this correlation was also noted in eyes with progressive glaucoma. The OCT en face structural images may be an alternative to red-free photography for identifying progressive RNFL defects in eyes with glaucoma.

To evaluate and compare the utility of ganglion cell complex with peripapillary retinal nerve fibre layer and optic nerve head measurements for detection of localized defects in patients with preperimetric glaucoma using spectral-domain optical coherence tomography. Prospective study. Preperimetric glaucoma patients. A total of 105 eyes with preperimetric glaucoma and 68 age- and refractive error-matched control eyes were enrolled. The ability to detect localized retinal nerve fibre layer defects by RTVue-100 spectral-domain optical coherence tomography (Optovue, Inc., Fremont, CA, USA) was assessed calculating the areas under receiver operating characteristic curves. The ability to detect localized retinal nerve fibre layer defects by spectral-domain optical coherence tomography. Global volume loss and superior ganglion cell complex thickness showed the largest area under receiver operating characteristic curve values (both areas under receiver operating characteristic curves 0.84, P < 0.001) among ganglion cell complex parameters. Average peripapillary retinal nerve fibre layer thickness afforded the best diagnostic capability (area under receiver operating characteristic curve 0.89, P < 0.001), whereas among optic nerve head parameters, the horizontal cup:disc ratio yielded the highest area under receiver operating characteristic curve (0.85, P < 0.001). No statistical difference was evident between the areas under receiver operating characteristic curves of the most informative parameters when the data were gathered from the three different sites (ganglion cell complex, peripapillary retinal nerve fibre layer, and optic nerve head) (P > 0.02). Ganglion cell complex thickness was significantly reduced in eyes with preperimetric glaucoma. Ganglion cell complex imaging using spectral-domain optical coherence tomography may be a useful ancillary modality for detection of early macular changes in glaucomatous eyes with localized retinal nerve fibre layer defects.

PurposeWe detected retinal nerve fiber layer (RNFL) defects using a confocal scanning laser ophthalmoscopy (CSLO) with both blue and green laser sources and evaluated image quality based on laser wavelength.MethodsThis was a retrospective observational case study. Blue and green CSLO images of 181 eyes with suspected glaucoma were evaluated and compared. Three independent observers identified the presence of RNFL defects and determined which CSLO imaging source provided superior visibility of the defect. After assessing the defect imaging by laser source, demographics and image quality indices of optical coherence tomography between blue better and green better groups were analyzed.ResultsBoth blue and green CSLO showed high discriminating ability for RNFL defects. The discriminating ability of blue CSLO was significantly greater than that of green CSLO (p = 0.004). Among eyes with a detectable RNFL defect, 61.8% were better visualized with the blue laser compared to the green laser. Compared with the blue better group, the green better group was significantly older (p = 0.009), had a greater proportion of females (p = 0.005), had poorer best-corrected visual acuity (p = 0.001), more severe cataracts (p = 0.001), lower signal strength (p = 0.003), and poor image quality indices (p = 0.001).ConclusionsBoth blue and green CSLO imaging was useful for detecting RNFL defects, but blue CSLO was superior to green CSLO in quality of RNFL defect imaging in most patients with clear media.

BackgroundTo investigate the hemodynamic characteristics of glaucoma eyes with disc hemorrhage (DH) by disc fluorescein angiography, and its relationship with glaucomatous changes of the optic disc and surrounding retinal nerve fiber layer (RNFL).MethodsThis study included 35 glaucoma eyes with DH who were followed up at least 5 years and had DH at presentation. Eyes were classified as eyes with DH at the border of localized RNFL defects and eyes with DH not related to localized RNFL defects. Prevalence of DH and location of the proximal border were recorded from disc photographs. Fluorescein angiography was performed 3 months after detecting the DH. Arm-retina time, arteriovenous transit time, disc filling time, choroidal filling time, and venous filling time were measured as retinal circulation parameters. The presence of disc filling defects and disc leaks were evaluated.ResultsThere were 19 (54.3%) eyes with DH accompanying localized RNFL defects. The arm-retina time was prolonged in eyes with DH not related to RNFL defects (P = 0.044) and the arteriovenous transit time was prolonged in eyes with DH accompanying RNFL defects (P = 0.029). Among eyes with DH accompanying RNFL defects, 11 (57.9%) had vessel filling defects or delayed filling indicating blood flow stasis at the cup margin proximal to where DH occurred. Eyes with DH not related to RNFL defects did not show vessel filling defects or delayed filling.Conclusions and RelevanceEyes with DH related to RNFL defects showed prolonged arteriovenous transit time and had frequent vessel filling defects or delayed filling indicating blood flow stasis and thrombus formation at the site DH occurred. These findings suggest that vascular and hemodynamic changes due to glaucomatous structural changes cause DH in relation to localized RNFL defects.

Certain features of the lamina cribrosa may be associated with increased risk of glaucoma progression. To compare the rates of retinal nerve fiber layer (RNFL) thinning in patients with open-angle glaucoma with or without lamina cribrosa (LC) defects and to evaluate factors associated with the rate of glaucoma progression in eyes with LC defects. This longitudinal cohort study designed in September 2017 and conducted at a tertiary glaucoma center in California included 51 eyes of 43 patients with LC defects and 83 eyes of 68 patients without LC defects followed up for a mean (SD) of 3.5 (0.8) years from April 2012 to May 2017. Focal LC defects were detected using swept-source optical coherence tomographic images. All participants underwent visual field testing and spectral-domain optical coherence tomography for RNFL thickness measurements every 6 months. Univariate and multivariable random-effects models were used to compare the rate of local and global RNFL loss. The mean (95% CI) age at baseline for individuals with LC defects was 69.5 (65.4 to 73.6) years, and for those without LC defects, it was 69.6 (67.2-72.0) years; 18 individuals (41%) with LC defects and 35 individuals (51%) without LC defects were men; 6 individuals (14%) with LC defects and 17 individuals (25%) without were African American. The mean (95% CI) rate of global RNFL loss in eyes with LC defects was 2-fold faster than that in eyes without LC defects (-0.91 [-1.20 to -0.62] vs -0.48 [-0.65 to -0.31] μm/y; difference, -0.43 [-0.76 to -0.09] μm/y; P = .01). The rate of RNFL thinning was faster in the LC defect sectors than that in the unaffected sectors (difference, -0.90 [95% CI, -1.68 to -0.12] μm/y, P = .02). Thinner corneal thickness was the only factor that was associated with a faster rate of RNFL loss in eyes with LC defects (β2 = -0.09 [95% CI, -0.14 to -0.04], P = .001). No association was found between mean intraocular pressure during follow-up and the mean rate of RNFL thinning in eyes with LC defects (β2, -0.05 [95% CI, -0.17 to 0.06], P = .36). These data suggest that LC defects are an independent risk factor for RNFL thinning and that glaucoma progression may correspond topographically to the LC defect location. Thinner corneal thickness in eyes with LC defects was associated with faster further glaucoma progression. In the management of open-angle glaucoma, LC findings may inform the likelihood and rate of glaucoma progression.

Deep Optic Nerve Head Structures Associated With Increasing Axial Length in Healthy Myopic Eyes of Moderate Axial Length

To investigate whether retinal nerve fiber layer (RNFL) thickness is decreased in patients with hematologic malignancy using optical coherence tomography (OCT). This prospective, observational cross-sectional study included 65 eyes from 34 patients with hematologic malignancy and 72 healthy control eyes. OCT-measured RNFL thickness parameters (average, 4 quadrants, and 12 clock-hour thickness) and RNFL defect in red-free photo were compared between patients with hematologic malignancy and controls. Among average, quadrant, and clock-hour map, the only 11-o'clock RNFL in patients with hematologic malignancy was statistically thinner than in controls (P=0.021). The RNFL defect was detected in 21/65 (32.3%) patients with hematologic malignancy and in 5/72 (6.9%) controls (P<0.001). In patients with hematologic malignancy, the mean RNFL thickness was significantly lower in the severe and moderate anemia groups compared with the mild anemia group (P=0.011). In the generalized estimating equations model, the mean hemoglobin level was associated with RNFL thickness while correcting for inter-eye correlation, age, and refraction error (coefficient=3.685, P=0.006). The RNFL defect was frequently observed, and the RNFL was thinner in severe anemic patients with hematologic malignancy. These results suggest that chronic anemia may be a factor of RNFL loss.