Localized Retinal Nerve Fiber Layer Defects Research Articles

Clinical Characteristics and Associated Factors to the Development of Glaucoma in Eyes With Myopic Optic Neuropathy

PurposeTo observe the development of glaucoma in myopic eyes with and without myopic optic neuropathy (MON) and analyze associated factors to the development of typical glaucomatous damage. DesignA prospective, observational, cohort study MethodsA total of 233 myopic eyes with no definite evidence of glaucomatous damage were included in the study. Myopic patients without any retinal nerve fiber layer (RNFL) or visual field (VF) abnormalities were classified as myopic eyes without MON. Myopic patients with decreased RNFL at the superonasal (SN) or nasal area, and with corresponding VF defects either in the temporal or inferotemporal (IT) region, which is different from glaucomatous damage, were classified as myopic eyes with MON. Myopic eyes that developed glaucoma were defined by the presence of glaucomatous VF in the SN region including defects in Bjerrum area, or a new localized RNFL defect in the IT region on red-free photography or RNFL OCT. Disc morphological features and optic nerve head (ONH) parameters of two groups were compared. Hazard ratios for the association between baseline factors and conversion to glaucoma were obtained using Cox regression analysis. ResultsMean follow-up period was 11.66 ± 2.86 years. Myopic eyes with MON had a thinner average peripapillary RNFL thickness (P < 0.001), worse MD of the VF (P = 0.031), a higher percentage of IT VF defects (P < 0.001), smaller torsion degree (P = 0.047), and greater LCD (P = 0.022). Myopic eyes with MON who developed glaucoma had a thinner average peripapillary RNFL thickness (P = 0.009), greater PPA area (P = 0.049), greater LCD (P < 0.001), and thinner LCT (P < 0.001). Thinner baseline temporal RNFL thickness (HR, 0.956; 95% CI, 0.928–0.986; P = 0.004), greater baseline LCD (HR, 1.003; 95% CI, 1.000–1.005; P = 0.022), and greater PPA area (HR, 1.000; 95% CI, 1.000–1.003; P = 0.050) were significantly associated factors with glaucoma development in the Cox regression analysis. ConclusionMyopic eyes with MON have a greater risk to develop glaucoma compared to myopic eyes without MON. Myopic eyes with MON had larger PPA area, greater LCD, and thinner temporal peripapillary RNFL, indicating that accompanying structural weakness due to myopia, especially at the temporal side of the optic nerve head and the peripapillary sclera, increases the risk of glaucoma in myopic eyes with MON.

Factors Associated with Vascular Changes at the Level of Retinal Ganglion Cell Axon versus Soma/Dendrite in Glaucoma Patients.

Superficial and deep macular vessel density (VD) is decreased in eyes with glaucoma. Superficial VD comprises both the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GC/IPL), and various terms have been used previously to describe the layers of macular VD. In our study, we readjusted the macular segmentation. We obtained RNFL and GC/IPL VDs separately to evaluate VD changes of axon versus soma/dendrite of the retinal ganglion cells (RGCs) in detail. We included 66 eyes of normal tension glaucoma patients with inferior localized RNFL defects solely impacting the inferior hemiretina. Macular VD was measured as RNFL VD and GC/IPL VD. VD ratio was calculated by dividing the VD from the affected hemiretina by the VD from the unaffected hemiretina. RNFL VD ratio was related to RNFL and GC/IPL thicknesses (p = 0.005, p = 0.001), whereas GC/IPL VD ratio was not (p = 0.596, p = 0.783). A lower GC/IPL VD ratio was associated with lower RNFL VD (p = 0.017) and systemic hypertension (p = 0.03) in multivariate analysis. Patients with a reduced GC/IPL VD ratio were more prone to poor visual field defects (p = 0.022) and paracentral scotoma (p = 0.046) and more likely to be on treatment for systemic hypertension (p = 0.024). Therefore, glaucoma patients on systemic hypertension treatment and reduced GC/IPL VD require cautious management.

Association between localized retinal nerve fiber layer defects in nonglaucomatous eyes and metabolic syndrome: a propensity score-matched analysis.

We investigated the association between metabolic syndrome and localized retinal nerve fiber layer (RNFL) defects in nonglaucomatous subjects. We 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. Subjects 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. Localized 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.

Discrepancy between peripapillary retinal and choroidal microvasculature and the rate of localized retinal nerve fiber layer thinning in glaucoma

This observational case series study is conducted to compare the extent of microvasculature impairment in the peripapillary retina and choroid in eyes with primary open-angle glaucoma (POAG), and to investigate the association of the discrepancy between the microvasculature impairments of each layer with the rate of progressive retinal nerve fiber layer (RNFL) thinning. A total of 88 POAG eyes with a localized RNFL defect were enrolled, including 67 eyes with and 21 eyes without choroidal microvasculature dropout (CMvD). Circumferential widths of retinal microvascular impairment (RMvI) and CMvD were measured, and eyes were classified based on the relative width of CMvD to RMvI (CMvD/RMvI ratio). The rate of RNFL thinning was determined by linear regression based on ≥ 5 serial OCT examinations. Thinner global RNFL and worse visual field mean deviation at baseline were associated with a larger circumferential width of the RMvI, whereas the presence of cold extremities, lower mean arterial pressure and thinner juxtapapillary choroid were associated with a larger circumferential width of the CMvD. The rate of global RNFL thinning was faster in eyes with larger relative CMvD width than in eyes with equal CMvD and RMvI widths and in eyes without CMvD (P = 0.001). Lower mean arterial pressure (P = 0.041), larger CMvD width (P = 0.046), larger CMvD/RMvI ratio (P = 0.041), and detection of disc hemorrhage during the follow-up (P = 0.013) were significant factors associated with faster global RNFL thinning. Larger CMvD width relative to RMvI width may be indicative of an increased risk of faster RNFL thinning in POAG with localized RNFL defect. Comparing the microvasculature impairment in individual layers may help predict more rapid glaucoma progression.

Microvasculature Dropout and Development of Normal Tension Glaucoma in Glaucoma Suspects: The Normal Tension Glaucoma Suspect Cohort Study

To investigate the contribution of vessel parameters to identify normal tension glaucoma (NTG) suspects at risk of NTG development. Multicenter prospective cohort study. A total of 307 eyes of 307 NTG suspects having intraocular pressure within the normal range; a suspicious optic disc, but without definite localized retinal nerve fiber layer (RNFL) defects; and a normal visual field (VF). To measure laminar vessel density (VD), the VD was measured in the intradisc region from images of the deep vascular layers of optical coherence tomography angiography (OCT-A). Conversion to NTG was defined either by a new localized RNFL defect in the superotemporal or inferotemporal region, or the presence of a glaucomatous VF defect on 2 consecutive tests according to the pattern deviation plots. Conversion to NTG. In total, 73 (23.8%) of the 307 NTG suspects converted to NTG during the follow-up period of 59.84 ± 12.44 months. Detection rate of microvasculature dropout (MvD) was significantly higher in NTG suspects who progressed to NTG (50.7%) than in those who did not (6.4%; P < .001). The macular deep VD (P=.006) and laminar deep VD (P=.004) were significantly lower in NTG suspects who progressed to NTG. The presence of MvD (P < .001) and lower laminar deep VD (P=.006) were significantly associated with NTG conversion. NTG suspects with baseline MvD or a lower laminar deep VD on OCT-A had a higher risk of conversion.

Predicting the development of normal tension glaucoma and related risk factors in normal tension glaucoma suspects

This study investigated the predicted risk factors for the development of normal-tension glaucoma (NTG) in NTG suspects. A total of 684 eyes of 379 NTG suspects who were followed-up for at least 5 years were included in the study. NTG suspects were those having (1) intraocular pressure within normal range, (2) suspicious optic disc (neuroretinal rim thinning) or enlarged cup-to-disc ratio (≥ 0.6), but without definite localized retinal nerve fiber layer (RNFL) defects on red-free disc/fundus photographs, and (3) normal visual field (VF). Demographic, systemic, and ocular characteristics were determined at the time of the first visit via detailed history-taking and examination of past medical records. Various ocular parameters were assess using spectral-domain optical coherence tomography and Heidelberg retinal tomography. Conversion to NTG was defined either by the presence of a new localized RNFL defect at the superotemporal or inferotemporal region on disc/fundus red-free photographs, or presence of a glaucomatous VF defect on pattern standard deviation plots on two consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. In total, 86 (12.6%) of the 684 NTG suspects converted to NTG during the follow-up period of 69.39 ± 7.77 months. Significant (P < 0.05, Cox regression) risk factors included medication for systemic hypertension, longer axial length, worse baseline VF parameters, thinner baseline peripapillary RNFL, greater disc torsion, and lamina cribrosa (LC) thickness < 180.5 μm (using a cut-off value obtained by regression analysis). Significant (P < 0.05, Cox regression) risk factors in the non-myopic NTG suspects included medication for systemic hypertension and a LC thinner than the cut-off value. Significant (P < 0.05, Cox regression) risk factors in the myopic NTG suspects included greater disc torsion. The results indicated that 12.6% of NTG suspects converted to NTG during the 5–6-year follow-up period. NTG suspects taking medication for systemic hypertension, disc torsion of the optic disc in the inferotemporal direction, and thinner LC of the optic nerve head at baseline were at greater risk of NTG conversion. Related baseline risk factors were different between myopic and non-myopic NTG suspects.

Optic disc morphology in primary open-angle glaucoma versus primary angle-closure glaucoma in South India.

Purpose:The aim of this study was to investigate the optic disc morphology in primary angle-closure glaucoma (PACG) versus primary open-angle glaucoma (POAG) in South Indians.Methods:A total of 60 patients (60 eyes) with PACG and 52 patients (52 eyes) with POAG were included in a cross-sectional observational study. The glaucoma diagnosis was based on a glaucomatous appearance of the optic disc correlating with visual field defects. The glaucoma was graded as early, moderate, or severe, depending upon perimetric loss. All patients underwent an ophthalmic evaluation, including visual field examination and planimetric analysis of 30° stereoscopic color optic disc photographs.Results:The POAG and PACG groups did not differ significantly in a disc or rim area, rim width, and frequencies of disc hemorrhages or rim notches. However, early POAG group (n = 15) had a significantly deeper cup depth (P = 0.01), larger beta zone (P = 0.01), and a higher frequency of localized retinal nerve fiber layer (RNFL) defects (P = 0.02) than early PACG (n = 20).Conclusion:In the early stage of the disease, POAG compared to PACG may be characterized by deeper disc cupping, a larger beta zone of peripapillary atrophy, and a higher frequency of localized RNFL defects. Such differences in early glaucoma may suggest differences in pathophysiology in POAG and PACG.

Defective angles of localized retinal nerve fiber layer reflect the severity of visual field defect- a cross-sectional analysis

BackgroundIn order to detect glaucomatous optic nerve damages early on and evaluate the severity of glaucoma, a previously developed analytic method based on photographic retinal nerve fiber layer (RNFL) angle defect was proposed. However, the correlation between these defective angles and the severity of visual field defect has not been verified. This study aimed to confirm the correlation described above.MethodsWe reviewed a total of 227 glaucomatous eyes (38 enrolled, 189 excluded) during an interval of 5 years. The angles of all eyes were measured on RNFL photograph, of which angle α is the angular width between the macula center and the proximity of RNFL defect, and angle β (+c) is the sum of angular width(s) of localized RNFL defect. The severity of visual field defect was determined by mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI). Correlation analysis was performed on angle α and angle β (+c) with the presence of central scotoma and visual field defect parameters, respectively.ResultsAngle β (+c) showed significant correlation with MD (P = 0.007), PSD (P = 0.02), VFI (P = 0.03), and average RNFL thickness (P = 0.03). No correlation was found between angle α and the presence of central scotoma.ConclusionsIn conclusion, measuring the angular width of localized RNFL defect is a viable method for determining the severity of visual field defect.

Patterns of glaucoma progression in retinal nerve fiber and macular ganglion cell-inner plexiform layer in spectral-domain optical coherence tomography.

To evaluate the progressive changes of circumpapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses measured by spectral-domain optical coherence tomography (Cirrus SD-OCT) in open-angle glaucoma. One hundred-fourteen eyes of open-angle glaucoma patients with localized RNFL defect who had 3years' worth of annual RNFL photography and OCT measurements were enrolled in this retrospective study. The progression rates of serial RNFL and GCIPL thicknesses (µm), angular width (°) and area (mm2) of defect on RNFL and GCIPL deviation maps were determined by linear mixed-effect models. Over a mean follow-up period of 3.16years, 50 patients out of a total of 114 patients were classified as progressors based on the structural evaluation. The progressors showed significantly higher progression rates in average, 6 and 11 o'clock sector RNFL thicknesses, angular width and area of defect in RNFL deviation map, as well as inferotemporal and minimum GCIPL thicknesses than the non-progressors. The thicknesses of the 6 o'clock sector RNFL and minimum GCIPL exhibited the highest reduction rates among the RNFL and GCIPL parameters assessed, respectively. When evaluating glaucoma progression by OCT, careful observation of the average, 6 and 11 o'clock sectors in RNFL and inferotemporal and minimum GCIPL thicknesses can be helpful. We can effectively assess early changes of glaucoma progression with GCIPL thickness as well as RNFL thickness.

Diagnostic Ability of Retinal Nerve Fiber Layer Thickness Deviation Map for Localized and Diffuse Retinal Nerve Fiber Layer Defects.

Purpose. To evaluate the diagnostic ability of the retinal nerve fiber layer (RNFL) deviation map for glaucoma with localized or diffuse RNFL defects. Methods. Eyes of 139 glaucoma patients and 165 healthy subjects were enrolled. All participants were imaged with Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA, USA). A RNFL defect was defined as at least 10 contiguous red (<1% level) superpixels in RNFL deviation map. The area, location, and angular width of RNFL defects were automatically measured. We compared sensitivities, specificities, and area under the receiver operating characteristic curves (AUCs) of RNFL deviation map and circumpapillary RNFL thickness for localized and diffuse RNFL defects. Subgroup analysis was performed according to the severity of glaucoma. Results. For localized defects, the area of RNFL defects (AUC, 0.991; sensitivity, 97%; specificity, 90%) in deviation map showed a higher diagnostic performance (p = 0.002) than the best circumpapillary RNFL parameter (inferior RNFL thickness; AUC, 0.914; sensitivity, 79%; specificity, 92%). For diffuse defects, there was no significant difference between the RNFL deviation map and circumpapillary RNFL parameters. In mild glaucoma with localized defect, RNFL deviation map showed a better diagnostic performance than circumpapillary RNFL measurement. Conclusions. RNFL deviation map is a useful tool for evaluating glaucoma regardless of localized or diffuse defect type and has advantages over circumpapillary RNFL measurement for detecting localized RNFL defects.

OCT Angiography of the Peripapillary Retina in Primary Open-Angle Glaucoma.

The purpose of this study was to investigate the topographic relationship between the decreased parapapillary retinal microvasculature as assessed by optical coherence tomography angiography (OCTA) and retinal nerve fiber layer (RNFL) defect in eyes with primary open-angle glaucoma (POAG) and a localized RNFL defect. The peripapillary retinal circulation was evaluated using the OCTA centered on the optic nerve head in 98 POAG eyes having a localized RNFL defect and 45 healthy control eyes. A vascular impairment (VI) was identified in OCTA by the presence of a sign indicating decreased microvasculature. The frequencies of VI were compared between the POAG and control groups, and the topographic correlation between the VI and the RNFL defect identified in red-free fundus photographs was determined in the POAG group. The VI was observed as an area of decreased density of the microvascular network of the retina in 100% of the POAG eyes. The VI exactly coincided with the RNFL defect evident in red-free fundus photographs in terms of both the location and extent (Pearson's correlation coefficient = 0.997 and 0.988, respectively, all P < 0.001). None of the control eyes exhibited VI in OCTA. Decreased parapapillary microvasculature of the retina determined by OCTA was found at the location of RNFL defect in POAG patients. This finding suggests that the decreased retinal microvasculature is likely secondary loss or closure of capillaries at the area of glaucomatous RNFL atrophy.

Macular Ganglion Cell Inner Plexiform Layer Thickness in Glaucomatous Eyes with Localized Retinal Nerve Fiber Layer Defects.

PurposeTo investigate macular ganglion cell–inner plexiform layer (mGCIPL) thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects on stereophotographs.Methods112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) subjects had standard automated perimetry (SAP), optical coherence tomography (OCT) imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs.Result47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P<0.001) and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 μm, P = 1.000). The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior) mGCIPL was thinnest in the same hemiretina in 26 eyes (90%). Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001) and inferior mGCIPL (P = 0.030) compared to glaucomatous eyes without a visible RNFL defect.ConclusionThe current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect.

Characteristics of Retinal Nerve Fiber Layer Defect in Nonglaucomatous Eyes With Type II Diabetes.

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.

Ten-Year Incidence of Retinal Nerve Fiber Layer Defects: The Beijing Eye Study 2001/2011.

We examined the 10-year incidence of localized retinal nerve fiber layer defects (RNFLDs) and associated factors in adult Chinese. The population-based longitudinal Beijing Eye Study, which included 4439 subjects (age, 40+ years) in 2001, was repeated in 2011 with 2695 subjects participating (66.4% of the survivors). Color fundus photographs taken at baseline and 10 years later were examined for localized RNFLDs, defined as wedge-shaped defects running toward the optic disc. Fundus photographs were available for 2422 (89.9%) subjects. Incident-localized RNFLDs were detected in 114/2422 persons (4.7% ± 0.2%) or 139/4867 eyes (2.9% ± 0.2%). A total of 25 (22%) persons had incident-localized RNFLDs bilaterally, and 89 (78%) persons unilaterally. Among the 114 persons with incident RNFLDs, 78 persons showed newly developed localized RNFLDs, while 36 subjects showed an enlargement of a preexisting localized RNFLD. In binary logistic regression analysis, a higher 10-year incidence of localized RNFLDs was significantly associated with a higher prevalence of arterial hypertension (P = 0.002; odds ratio [OR], 2.31; 95% confidence interval (CI), 1.35, 3.97), higher diastolic blood pressure (P = 0.02; OR, 1.02; 95% CI, 1.004,1.04), higher prevalence of previous cerebrovascular infarctions (P = 0.007; OR, 2.61; 95% CI, 1.30, 5.22), younger age (P = 0.01; OR, 0.97; 95% CI, 0.94, 0.99), higher prevalence of diabetic retinopathy (P = 0.001; OR, 4.70; 95% CI, 1.92, 11.5), higher prevalence of open-angle (P < 0.001; OR, 39.8; 95% CI, 19.7, 80.5) and angle-closure (P < 0.001; OR, 21.3; 95% CI, 7.90, 57.5) glaucoma, and thinner retinal nerve fiber layer (P < 0.001; OR, 0.97; 95% CI, 0.95, 0.98). The 10-year incidence of localized RNFLDs in adult Chinese is 4.7% ± 0.2%. It is strongly associated with arterial hypertension and higher prevalence of cerebrovascular infarcts, in addition to ocular reasons, such as glaucoma and diabetic retinopathy. Ophthalmologically normal subjects with incident-localized RNFLDs may be screened for arterial hypertension and cerebrovascular infarcts.

Optic disc hemorrhage is related to various hemodynamic findings by disc angiography.

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.

Retinal Nerve Fiber Layer Loss Is Associated with Urinary Albumin Excretion in Patients with Type 2 Diabetes

To identify the factors associated with retinal nerve fiber layer (RNFL) loss in patients with type 2 diabetes. Cross-sectional study. Ninety-six nonglaucomatous patients with type 2 diabetes without renal impairment (estimated glomerular filtration rate, ≥60 ml/minute per 1.73 m(2)). Eyes were divided into 2 groups based on the presence or absence of RNFL defects detected by red-free retinal fundus photography. All participants underwent an eye fundus examination, and the urinary albumin-to-creatinine ratio (ACR) was determined. A cardiovascular autonomic function test was performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to the Valsalva maneuver, and standing. Multiple logistic regression analyses were performed to determine potential risk factors related to the presence of RNFL defects in these patients. The association between RNFL defects and diabetic complications. Among the patients, 43 (44.8%) had localized RNFL defects (group 1), whereas the others (55.2%) did not (group 2). The RNFL defects occurred more frequently on the superior side (75.6% and 71.0% in right and left eyes, respectively) compared with the inferior side (13.8% and 0.0% in right and left eyes, respectively). Patients with RNFL defects (group 1) had significantly higher rates of diabetic retinopathy (60.5%) compared with those without RNFL defects (group 2; 32.1%; P = 0.007). The urinary ACR was significantly higher in patients with RNFL defects than in those without defects (45.3±72.1 μg/mg vs. 15.4±17.3 μg/mg creatinine, respectively; P = 0.015), whereas autonomic function test grading was similar between the groups. The urinary ACR was the only factor related to visual field defect location in both univariate (P = 0.021) and multivariate (P = 0.036) logistic regression analyses after adjusting for age; gender; presence of diabetic retinopathy; diabetes duration; smoking; statin use; and antiplatelet, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker treatment. Urinary albumin excretion was associated with nerve fiber layer loss in patients with type 2 diabetes. Careful examination of the optic nerve head may be necessary, particularly in patients with type 2 diabetes exhibiting albuminuria.

Quantitative Analysis of Localized Retinal Nerve Fiber Layer Defects Using Spectral Domain Optical Coherence Tomography

To compare the topographic features of localized retinal nerve fiber layer (RNFL) defects presented in red-free RNFL photography and spectral domain optical coherence tomography (SD-OCT), and to evaluate the correlation with structural and functional parameters. Sixty eyes with localized RNFL defects in red-free RNFL photographs were included. RNFL thickness map and significance map were obtained by SD-OCT. The angular location, angular width, and area of localized RNFL defects were measured and compared among RNFL thickness map, significance map (red, <1% level; yellow, <5% level), and RNFL photograph. The RNFL defect areas were analyzed by their correlations with structural and functional parameters. The RNFL defect area of RNFL thickness map was significantly greater than those of red significance map, and smaller than those of RNFL photograph and yellow significance map (all P<0.001). RNFL thickness map showed a significantly narrower angular width than RNFL photograph and yellow significance map (all P<0.001). The area, angular width, and angular location of localized RNFL defects in RNFL photographs strongly correlated with those of RNFL thickness maps and significance maps (all r≥0.741, P<0.001). The relationship between RNFL defect area and structural-functional parameters was also significant. The high topographic correlations in RNFL defects between RNFL photography and SD-OCT RNFL maps suggest the validity of SD-OCT RNFL imaging for detecting localized glaucomatous RNFL damage. In addition, structural and functional parameters are closely related to RNFL defect areas. Quantitative measurements of RNFL defects might be valuable for glaucoma diagnosis.

Detecting the progression of normal tension glaucoma: a comparison of perimetry, optic coherence tomography, and Heidelberg retinal tomography.

PurposeWe compared the abilities of Stratus optical coherence tomography (OCT), Heidelberg retinal tomography (HRT) and standard automated perimetry (SAP) to detect the progression of normal tension glaucoma (NTG) in patients whose eyes displayed localized retinal nerve fiber layer (RNFL) defect enlargements.MethodsOne hundred four NTG patients were selected who met the selection criteria: a localized RNFL defect visible on red-free fundus photography, a minimum of five years of follow-up, and a minimum of five reliable SAP, Stratus OCT and HRT tests. Tests which detected progression at any visit during the 5-year follow-up were identified, and patients were further classified according to the state of the glaucoma using the mean deviation (MD) of SAP. For each test, the overall rates of change were calculated for parameters that differed significantly between patients with and without NTG progression.ResultsForty-seven (45%) out of 104 eyes displayed progression that could be detected by red-free fundus photography. Progression was detected in 27 (57%) eyes using SAP, 19 (40%) eyes using OCT, and 17 (36%) eyes using HRT. In early NTG, SAP detected progression in 44% of eyes, and this increased to 70% in advanced NTG. In contrast, OCT and HRT detected progression in 50 and 7% of eyes during early NTG, but only 30 and 0% of eyes in advanced NTG, respectively. Among several parameters, the rates of change that differed significantly between patients with and without progression were the MD of SAP (p = 0.013), and the inferior RNFL thickness (p = 0.041) and average RNFL thickness (p = 0.032) determined by OCT.ConclusionsSAP had a higher detection rate of NTG progression than other tests, especially in patients with advanced glaucoma, when we defined progression as the enlargement of a localized RNFL defect. The rates of change of the MD of SAP, inferior RNFL thickness, and average RNFL thickness differed between NTG patients with and without progression.

Nonglaucomatous Localized Retinal Nerve Fiber Layer Defects in Behçet Uveitis

To describe nonglaucomatous retinal nerve fiber layer (RNFL) defects in patients with Behçet uveitis. Cross-sectional study and observational case series. We reviewed the clinical photographs of patients with Behçet uveitis (n= 259), ocular toxoplasmosis (n= 120), and multiple sclerosis (MS)-associated uveitis (n= 40) for the presence of localized RNFL defects. Behçet patients with localized RNFL defects were invited to participate in a prospective evaluation including standard automated perimetry, spectral-domain optical coherence tomography (SD OCT), and RNFL thickness analysis. Main outcome measures were the prevalence of localized RNFL defects, perimetric and SD OCT findings, and RNFL thickness analysis. Sixty-two patients with Behçet uveitis (24%) had localized RNFL defect(s) without any visible scar. Twenty patients (17%) with ocular toxoplasmosis had a localized RNFL defect associated with a retinochoroidal scar in all. None of the MS patients had a localized RNFL defect. Of the 19 patients (24 eyes) with RNFL defect associated with Behçet uveitis who returned for follow-up, there was a corollary thinning on SD OCT B-scan in all and a corresponding visual field defect in 83%. RNFL thickness analysis was within normal limits in 54%, but revealed thinning in the thickness profile scale in 46% and in the pie chart in 21%. In Behçet uveitis, localized RNFL defects may be caused by microvascular ischemia at the optic nerve head and/or at the posterior pole and may serve as a helpful ocular diagnostic clue and an indicator of posterior pole involvement, a risk factor for poor visual prognosis.

Topographic Profiles of Retinal Nerve Fiber Layer Defects Affect the Diagnostic Performance of Macular Scans in Preperimetric Glaucoma

To evaluate the influence of topographic profiles (i.e., inner directional angle and angular width) of localized retinal nerve fiber layer (RNFL) defects on the diagnostic performance of macular ganglion cell-inner plexiform layer (GCIPL) thickness in discriminating preperimetric glaucoma (PPG) eyes from normal control eyes. The ganglion cell analysis algorithm in Cirrus OCT was performed to determine the macular GCIPL thickness. Areas under the receiver operating characteristic curves (AUROCs) and the sensitivities/specificities based on an internal normative database were evaluated. The effect of the inner directional angle and the angular width of localized RNFL defects on the diagnostic performance of macular GCIPL parameters were evaluated by using linear-by-linear association analysis and logistic regression analysis. Ninety-two patients with PPG and 92 age-matched healthy control subjects were enrolled in this study. The AUROC of the best parameters in macular GCIPL was 0.823 (inferotemporal sector), which showed no significant difference in comparison to the best parameters of peripapillary RNFL (7 o'clock sector, 0.764) and optic nerve head (rim area, 0.767) (for all comparisons, P > 0.05). A significant linear association was observed between the inner directional angle of RNFL defects and the sensitivity of macular GCIPL parameters for detecting RNFL defects. The angular width of RNFL defects was not significantly associated with the sensitivity of macular GCIPL parameters. The diagnostic ability of macular GCIPL parameters was comparable to that of peripapillary RNFL and ONH parameters in PPG. The inner directional angle of RNFL defects, but not the angular width, affects the diagnostic sensitivity of macular GCIPL parameters.