Masanori Hangai

Effects of Sex and Age on the Normal Retinal and Choroidal Structures on Optical Coherence Tomography

Abstract Optical coherence tomography (OCT) has become an essential tool in ophthalmology. Advances in OCT technology have made it possible to measure the thickness of the retina, specific retinal layers, and the choroid. In the present study, the body of the literature documenting the normal retinal and choroidal thickness are reviewed and the effects of sex, age, and axial length on retinal/choroidal thickness are discussed. Macular, retinal layer, and choroidal thickness measured on OCT images in normal eyes showed significant variations by sex and age. Macular retinal thickness was greater in men than in women, especially in the center, inner ring, and outer temporal ring areas as defined by the Early Treatment Diabetic Retinopathy Study (ETDRS). Moreover, inner retinal thickness decreased with increasing age and choroidal thickness was greater in men than in women and was negatively correlated with age and axial length. These findings provide information that should be considered in analyses of retinal or choroidal thickness in OCT studies of retinal diseases and glaucoma.

Alterations in the Neural and Connective Tissue Components of Glaucomatous Cupping After Glaucoma Surgery Using Swept-Source Optical Coherence Tomography

PURPOSE To visualize changes in deep optic nerve head (ONH) structures following glaucoma surgery using (3-dimensional [3D]) swept-source optical coherence tomography (SS-OCT) and to determine the clinical and structural factors associated with postoperative lamina cribrosa (LC) and prelaminar neural tissue (PLT) changes. METHODS In this prospective observational case series, SS-OCT thin-sliced datasets of the ONH covering a 3- × 3-mm area comprised of 256 B-scans (interval between scans = ∼12 μm) were obtained before and 3 months after the surgery and evaluated in 73 eyes of 73 patients with glaucoma. Bruchs membrane opening (BMO) and anterior LC boundary were manually delineated by two methods; one in every four B-scans (64 B-scans per eye) and 15 equally spaced horizontal B-scans in BMO area, excluding both ends (interval between scans = 96-120 μm). After former delineation, the point with maximum LC depth among 64 B-scans was automatically calculated, and LC depth and PLT thickness were averaged among 5 points adding 4 points 100 μm apart from this point vertically and horizontally. Associations between the percent change in LC depth and other clinical and structural parameters were tested for statistical analysis. RESULTS Lamina cribrosa depth and axial length significantly decreased and PLT thickness significantly increased after surgery. The percent change of maximum LC depth correlated significantly with the percent change of IOP (P = 0.008), baseline LC depth (P = 0.032), and visual field mean deviation (P = 0.035; at the point with maximum LC depth), while the percent change of axial length correlated with IOP reduction (P = 0.002) but not with visual field mean deviation. CONCLUSIONS Swept-source optical coherence tomography enables 3D analysis of deep ONH structures, and the change in LC depth after glaucoma surgery have association with IOP change and the severity of glaucomatous optic neuropathy.

Wide 3-dimensional macular ganglion cell complex imaging with spectral-domain optical coherence tomography in glaucoma.

PURPOSE To determine whether measurement of ganglion cell complex (GCC) thickness over a wide area (8-mm diameter) can improve the glaucoma-discriminating ability of spectral-domain optical coherence tomography (SD-OCT) compared to that in the standard macular area (6-mm diameter). METHODS Ninety-three subjects were enrolled, including 46 healthy eyes of 46 volunteers and 47 eyes of 47 glaucoma patients (23 eyes with preperimetric glaucoma [PPG] and 24 eyes with early glaucoma [EG]). All patients underwent SD-OCT raster scanning over a 9 mm × 9 mm square area centered on the fovea. Areas under the receiver operating characteristic curves (AROCs) were compared between wide sector (1-8-mm ring) and standard-size sector (1-6-mm ring) charts. RESULTS AROCs for average GCC thickness in the wide chart were significantly greater than those of the standard chart in eyes with PPG (0.928 vs. 0.891; P = 0.038), EG (0.912 vs. 0.861; P = 0.003), and both (0.920 vs. 0.876; P = 0.004). Overall, the AROCs of regional GCC thicknesses were nearly comparable between the middle ring (4-6 mm) and outer ring (6-8 mm). Coefficients of variation were 0.68% and 0.97% in the standard and wide sector charts, respectively, in eyes with PPG, and 0.45% and 0.72% in the standard and wide sector charts, respectively, in eyes with EG. CONCLUSIONS Addition of the GCC thickness outside the macula to the standard macular GCC thickness significantly increased the glaucoma-discriminating ability of SD-OCT.

Lamina Cribrosa Depth Variation Measured by Spectral-Domain Optical Coherence Tomography Within and Between Four Glaucomatous Optic Disc Phenotypes.

PURPOSE To study lamina cribrosa (LC) depth variation measured by spectral-domain optical coherence tomography (SD-OCT) in four glaucomatous optic disc phenotypes. METHODS In this cross-sectional study, 59 normal eyes and 180 open-angle glaucoma (OAG) eyes were grouped into 56 focally injured discs (FI), 30 generalized enlargement of the optic cup discs (GE), 69 myopic glaucomatous discs (MY), and 25 senile sclerotic discs (SS). They were imaged by enhanced depth imaging SD-OCT, obtaining multiple horizontal and vertical optic disc B-scans. Mean and maximum LC depths were measured relative to Bruchs membrane opening (BMO) and the anterior sclera (AS) reference planes. Lamina cribrosa depths were compared between and among the normal and OAG group disc phenotypes. Lamina cribrosa depth differences within groups were examined as well as the overlap between them. RESULTS Mean and maximum LC depths relative to the BMO and AS reference planes were greater in the OAG group than in the normal group (P < 0.0001). Among glaucomatous phenotypes, the GE group had the greatest (P < 0.001) and the SS group had the smallest (P < 0.05) mean and maximum LC depths. There was a wide range of LC depth overlap between the normal and SS groups, and a high proportion of SS eyes had LC depths within the 95% confidence interval of the normal group. CONCLUSIONS The LC was displaced posteriorly in OAG group compared to the normal group. The LC depth was significantly different among four glaucomatous disc phenotypes. The LC depth of the SS group was similar to the normal group.

Correlation between Lamina Cribrosa Tilt Angles, Myopia and Glaucoma Using OCT with a Wide Bandwidth Femtosecond Mode-Locked Laser

Purpose To measure horizontal and vertical lamina cribrosa (LC) tilt angles and investigate associated factors using prototype optical coherence tomography (OCT) with a broad wavelength laser light source. Design Cross sectional study. Methods Twenty-eight no glaucoma eyes (from 15 subjects) and 25 glaucoma eyes (from 14 patients) were enrolled. A total of 300 optic nerve head B-scans were obtained in 10 µm steps and the inner edge of Bruchs membrane opening (BMO) was identified as the reference plane. The vertical and horizontal angles between BMO line and approximate the best-fitting line for the surface of the LC were measured and potential associated factors were estimated with univariate and multivariate logistic regression analyses. Results The median (interquartile range) horizontal and vertical tilt angles were 7.10 (2.43–11.45) degrees and 4.15 (2.60–6.85) degrees in eyes without glaucoma and 8.50 (4.40–14.10) degrees and 9.30 (6.90–14.15) degrees in glaucoma eyes, respectively. The refractive errors had a statistically significant association with horizontal LC tilt angles (coefficients, −1.53 per diopter) and glaucoma had a significant correlation with vertical tilt angles (coefficients, 6.56) using multiple logistic regression analysis (p<0.001). Conclusions OCT allowed evaluation of the internal tilting of the LC compared with the BMO. The horizontal internal LC tilt angle was correlated with refractive errors, corresponding to myopic physiological changes, and vertical internal LC tilt was correlated with glaucoma, corresponding to glaucomatous pathological changes. These parameters have important implications for investigation of the correlation between myopia, glaucoma and LC morphological features.

Influence of clinical factors and magnification correction on normal thickness profiles of macular retinal layers using optical coherence tomography

Purpose To identify the factors which significantly contribute to the thickness variabilities in macular retinal layers measured by optical coherence tomography with or without magnification correction of analytical areas in normal subjects. Methods The thickness of retinal layers {retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCLIPL), RNFL plus GCLIPL (ganglion cell complex, GCC), total retina, total retina minus GCC (outer retina)} were measured by macular scans (RS-3000, NIDEK) in 202 eyes of 202 normal Asian subjects aged 20 to 60 years. The analytical areas were defined by three concentric circles (1-, 3- and 6-mm nominal diameters) with or without magnification correction. For each layer thickness, a semipartial correlation (sr) was calculated for explanatory variables including age, gender, axial length, corneal curvature, and signal strength index. Results Outer retinal thickness was significantly thinner in females than in males (sr2, 0.07 to 0.13) regardless of analytical areas or magnification correction. Without magnification correction, axial length had a significant positive sr with RNFL (sr2, 0.12 to 0.33) and a negative sr with GCLIPL (sr2, 0.22 to 0.31), GCC (sr2, 0.03 to 0.17), total retina (sr2, 0.07 to 0.17) and outer retina (sr2, 0.16 to 0.29) in multiple analytical areas. The significant sr in RNFL, GCLIPL and GCC became mostly insignificant following magnification correction. Conclusions The strong correlation between the thickness of inner retinal layers and axial length appeared to result from magnification effects. Outer retinal thickness may differ by gender and axial length independently of magnification correction.

Progressive Thinning of Regional Macular Thickness After Epiretinal Membrane Surgery

PURPOSE To determine the long-term changes in the regional macular thickness after idiopathic epiretinal membrane (ERM) excision and to determine whether there were correlations between the pre- and postoperative central macular thickness and the best-corrected visual acuity (BCVA). METHODS This was a prospective, interventional case series study of 53 eyes of 53 patients that underwent ERM removal with internal limiting membrane (ILM) peeling. Examinations were performed before, 1, 2, 3, 6, 9, 12, 24, 36, 48, and 60 months after the surgery. The average macular thicknesses in nine sectors outlined by the Early Treatment Diabetic Retinopathy Study were measured by spectral-domain optical coherence tomography. The final macular thicknesses of nine sectors of the 35 patients were compared with that of the normal fellow eyes. RESULTS All patients were followed for 36 months, and 21 patients were followed for 48 months. The thicknesses of all sectors progressively decreased for 48 months. The macula at 48 months was thinner than at 36 months (P < 0.0001-0.037) in all sectors. The final central and nasal sectors were significantly thicker than that of the fellow eyes. The final inner and outer temporal sectors were significantly thinner compared with the fellow eyes. There was no significant difference in the other sectors. The pre- and postoperative central macular thickness was significantly correlated with the postoperative BCVA at each examination. CONCLUSIONS A progressive thinning of the macula occurs with regional differences for at least 48 months. The temporal sector becomes thinner than the normal thickness.

Association of Myopic Optic Disc Deformation with Visual Field Defects in Paired Eyes with Open-Angle Glaucoma: A Cross-Sectional Study

Purpose To examine the association of myopia with the visual field (VF) defects in open-angle glaucoma (OAG) using paired eyes to eliminate the effect of unknown confounding factors that are diverse among individuals. Methods One hundred eighteen eyes of 59 subjects with myopia (spherical equivalent [SE] ≥ -2 diopter [D] and axial length ≥ 24.0 mm) whose intra-ocular pressure between paired eyes was similar and the mean deviation (MD) of the Humphrey VF test differed by more than 6 dB were included. Refractive errors (SE, axial length) and parameters associated with the papillary and parapapillary myopic deformation (tilt ratio, torsion angle, and β-zone parapapillary atrophy [PPA] area without Bruch’s membrane) were measured in each eye. The paired eyes were divided into worse and better eyes according to the MD of the VF, and parameters were compared between them. Further, multiple linear regression analysis was performed to examine the correlation of the difference in various parameters with the MD difference between paired eyes. Results The SE of all eyes was -6.39 ± 2.15 D (mean ± standard deviation) and axial length was 26.42 ± 1.07 mm. MD of the worse and better VF eyes were -13.56 ± 6.65 dB and -4.87 ± 5.32 dB, respectively. Eyes with worse VFs had significantly greater SE, axial length, tilt ratio, and PPA area without Bruch’s membrane than those with better VFs (all P < 0.05). In multiple linear regression analysis, the difference of the MD between paired eyes was significantly correlated with the difference in the tilt ratio and PPA area without Bruch’s membrane. Conclusion The myopic papillary and parapapillary deformations, but not refractive error itself, were related to the worse VF in paired eyes with OAG. This suggests that myopia influences the severity of the glaucomatous VF defects via structural deformation.

Differences in Relationship Between Macular Inner Retinal Layer Thickness and Retinal Sensitivity in Eyes With Early and Progressed Glaucoma

PURPOSE To determine if the relationship between retinal sensitivity and macular inner retinal layer thickness differs between primary open-angle glaucoma (POAG) with mild and advanced central visual field (VF) damage. METHODS One eye of 153 POAG patients was included. Using spectral-domain optical coherence tomography, we measured the average thickness of the macular ganglion cell-inner plexiform layers (GCIPLT) and the macular nerve fiber layer/GCIPL (ganglion cell complex [GCCT]) in a 0.9-mm-diameter ganglion cell displacement-adjusted circular area corresponding to the four central test points of the Humphrey Perimeter 24-2 program and correlated the results with the average retinal sensitivity (1/Lambert) at the corresponding test points, with adjustment for other confounding factors. RESULTS Ninety-three eyes had mild central and 60 eyes advanced central VF damage with an average total deviation (TD) of the four test points of greater than or equal to -4 decibels (dB) (mild group) and less than -4 dB (more severe group), respectively; the average mean deviations were -3.0 and -9.8 dB, respectively. In the mild group, the GCCT and GCIPLT were correlated significantly and positively with the average retinal sensitivity with partial regression coefficient of 0.007 and 0.005, respectively, and in the more severe group with partial regression coefficient of 0.019 = 0.007 + 0.012 (P = 0.007) and 0.010 = 0.005 + 0.005 (P = 0.078), respectively. The axial length and disc size were correlated with GCIPLT with marginal significance (P = 0.052 and P = 0.042). CONCLUSIONS The relationship between the macular GCC and GCIPL thickness and retinal sensitivity at the corresponding retinal areas differed between POAG with mild and advanced central VF damage.

Determinants and Characteristics of Bruch's Membrane Opening and Bruch's Membrane Opening–Minimum Rim Width in a Normal Japanese Population

Purpose To identify determinants of Bruchs membrane opening (BMO), and BMO–minimum rim width (BMO-MRW) and circumpapillary retinal nerve fiber layer thickness (RNFLT) centered on BMO center and characterize these parameters in a normal Japanese population. Methods Spectral-domain optical coherence tomography images of optic nerve head and circumpapillary and macular retina were obtained in 258 eyes of 258 normal Japanese with mean (standard deviation) age of 51.7 (18.2) years. BMO area, BMO-MRW, RNFLT (measured with a 3.5-mm-diameter circle scan) were all acquired and analyzed relative to the eye-specific fovea to BMO (FoBMO) axis. One randomly selected eye of each subject was analyzed. Multiple regression analysis was used to identify determinants to the parameters. Results BMO area, global BMO-MRW, RNFLT, and FoBMO angle averaged 2.06 (0.45) mm2, 305.5 (50.0) μm, 101.8 (9.6) μm, and −7.8° (3.8°), respectively. There was a modest correlation between global BMO-MRW and RNFLT (r = 0.337; P < 0.001), while the sectorwise correlations were highest in the superior-temporal sector (r = 0.500; P < 0.001) and lowest in the nasal sector (r = 0.117; P = 0.063). Global BMO-MRW and RNFLT declined with age at −1.04 μm/y (P < 0.001) and −0.12 μm/y (P = 0.001), and the former correlated negatively (P = 0.001) and the latter positively (P < 0.001) with BMO area after adjustment for other factors (R2 = 0.191 and 0.272, respectively). BMO area correlated positively with axial length (P = 0.023) and negatively with age (P < 0.001) (R2 = 0.157). Conclusions BMO-MRW and RNFLT declined with age with a difference between them in their relationship to BMO area. BMO area positively correlated with axial length and negatively with age.