Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Association of Bergmeister Papilla and Deep Optic Nerve Head Structures With Prelaminar Schisis of Normal and Glaucomatous Eyes.

PURPOSE: To investigate factors associated with the severity of prelaminar schisis (PLS) in heathy subjects and glaucoma patients. DESIGN: Prospective cross-sectional study. METHODS: A total of 217 eyes of 217 subjects (110 normal eyes and 107 open angle glaucoma eyes) were studied. Frequency and severity of PLS were compared between normal and glaucomatous eyes. Multivariate logistic models were used to assess factors associated with the severity of PLS. Factors considered were age, axial length, glaucomatous damage indices, Bruch membrane opening (BMO) and anterior scleral canal opening parameters, tractional forces (posterior vitreous staging and presence of Bergmeister papilla), circumpapillary choroidal thickness, lamina cribrosa (LC) parameters, and peripapillary scleral (PPS) angle. RESULTS: The frequency of PLS was 70.9% in normal eyes and 72.0% in glaucomatous eyes. There was no difference in frequency and severity between the groups. The presence of Bergmeister papilla was the strongest predictor of a more severe PLS in both normal and glaucomatous eyes (odds ratio [OR] + 9.78, 12.5; both P < .001). A larger PPS angle in normal eyes (OR = 1.19; P = .003) and a larger BMO area and a deeper LC depth in glaucomatous eyes (OR = 1.08, 1.05; both P = .038) were associated with severity of PLS. CONCLUSIONS: The severity of PLS was strongly associated with the presence of Bergmeister papilla, suggesting a traction-related phenomenon. Correlation of PLS severity with larger BMO area and deeper LC depth, which are optic nerve head structures associated with glaucoma, suggested its possible relationship with glaucomatous damage.

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

PURPOSE: To elucidate which swept-source optical coherence tomography (OCT)-derived optic nerve head (ONH) parameters are associated with longer axial length (AXL) in healthy myopic eyes. DESIGN: Prospective cross-sectional observational study. METHODS: Two hundred eleven healthy eyes of 140 participants (96 emmetropic-mild myopic [AXL: 22.2-24.5 mm], 83 moderately myopic [24.5-26.0 mm], and 32 highly myopic [26.0-27.4 mm] eyes) were enrolled. Bruch membrane opening (BMO), anterior scleral canal opening (ASCO) area and ovality, minimum rim width, parameters defining misalignment between the BMO and ASCO planes, OCT-defined region of perineural canal retinal epithelium atrophy and externally oblique choroidal border tissue, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), circumpapillary choroidal thickness (cpChT), lamina cribrosa parameters, and peripapillary scleral (PPS) angle were calculated from BMO-centered radial scans reconstructed from 3D raster scans. Multivariate linear mixed models were used to elucidate ONH parameters that are independently associated with AXL. RESULTS: Longer AXL was associated with a greater misalignment between ASCO and BMO planes, larger region of externally oblique choroidal border tissue, thinner cpChT, larger PPS angle, larger ASCO area, and thicker cpRNFLT (all P < .040 after Bonferroni's correction for number of included explanatory variables). CONCLUSIONS: A greater misalignment between BMO and ASCO planes, thinner choroid, a more posteriorly bowed PPS, an enlargement of ASCO, and thicker cpRNFLT were each associated with longer AXL. An enhanced understanding of these AXL-associated configurations should provide essential information to improve our ability to detect glaucoma-induced ONH morphology in myopic eyes.

The second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy.

PURPOSE: To describe the clinical and genetic findings of patients in the second Japanese family with Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). METHODS: Two patients (a 41-year-old male proband and his third son) underwent comprehensive ophthalmic examinations, including full-field and multifocal electroretinography (ERG). Sanger sequencing was performed to detect an EFEMP1 gene variant (p.Arg345Trp), which was identified as the only causative pathogenic variant. RESULTS: Genetic analysis revealed that both patients carried the heterozygous variant, but the other unaffected family members did not. Although the proband exhibited innumerable radially distributed drusen in both the posterior poles and good visual acuity at initial presentation, bilateral choroidal neovascularization (CNV) developed during the 15-year follow-up. The proband received 15 intravitreal anti-vascular endothelial growth factor (VEGF) injections in the left eye (LE) and two injections in the right eye (RE). At 56 years of age, his decimal best-corrected visual acuity was 0.1 and 1.2 in the LE and RE, respectively. Full-field ERG showed that while the rod and combined responses were within normal amplitudes, the cone and 30-Hz flicker responses had slightly decreased amplitudes. Multifocal ERG revealed attenuated central responses in the LE and decreased temporal responses in the RE. In the 20-year-old son, multifocal ERG showed normal responses in both eyes. CONCLUSION: This is the first report of ML/DHRD in a patient who developed bilateral CNV and received anti-VEGF treatment in both eyes. Although multifocal ERG exhibited worsening of macular function, the generalized photoreceptor function was preserved until middle age.

Characterization of laser speckle flowgraphy pulse waveform parameters for the evaluation of the optic nerve head and retinal circulation.

To characterize laser speckle flowgraphy (LSFG) pulse waveform parameters for ocular circulation evaluation, a multicenter, prospective, cross-sectional study was conducted in 111 eyes of 86 healthy Japanese individuals. Optic nerve head (ONH) tissue-area, vessel-area mean blur rate (MT and MV, respectively), and MT and MV pulse waveform parameters were obtained using LSFG and ONH structural parameters using planimetry. Multivariate linear mixed-effects modeled regression analysis identified factors contributing to MT- or MV-waveforms using age, gender, smoking history, body mass index, systolic and diastolic blood pressure, heart rate, intraocular pressure, axial length, disc, rim, and ß-peripapillary atrophy areas, MT or MV, central retinal artery, and vein equivalents (CRAE and CRVE) as explanatory variables. MT- and MV-waveforms significantly correlated with one or more systemic factors, consistent with previous studies. Following confounding factor adjustment, MT-Skew significantly negatively correlated with ß-PPA area (P = 0.026); MT- and MV-flow acceleration index positively correlated with CRAE, MT, and MV (P = 0.041-< 0.001), compatible with these parameters' observed correlations to systemic factors. Significantly negative correlations of the blowout score and acceleration time index to CRAE partly conflicted with their correlations to systemic factors, and other waveform parameters showed little correlation to ocular factors. Thus, Skew and flow acceleration index assisted the in vivo ocular circulation characterization.

Ocular and Systemic Factors Affecting Laser Speckle Flowgraphy Measurements in the Optic Nerve Head.

Purpose: To investigate the ocular and systemic factors related to glaucoma and to be adjusted for interindividual comparison of ocular blood flow measurement results by laser speckle flowgraphy (LSFG) obtained from the optic nerve head (ONH) in normal Japanese individuals. Methods: A multicenter, prospective cross-sectional study was conducted. The ONH tissue-area and vessel-area mean blur rate (MT and MV) were evaluated using LSFG and ONH structural parameters using planimetric methods. Multivariate linear mixed-effects modeled regression analysis was used to identify the contributing factors to the MT and MV. The explanatory variables were age; gender; smoking history; body mass index; mean arterial pressure (MAP); heart rate; intraocular pressure; axial length (AL); disc, rim, cup, and ß-peripapillary atrophy (ß-PPA) areas; and central retinal artery and vein equivalents. Results: In total, 195 eyes of 126 healthy individuals with an average age of 48.1 years were included. Multivariate analysis showed that MAP and disc area had a negative (P < 0.001) correlation, whereas ß-PPA area had a positive correlation with MT (P = 0.010). Age and AL had a negative correlation (P = 0.001 and P = 0.011, respectively), whereas cup area had a positive correlation (P = 0.012) with MV. Conclusions: Interindividual comparison of MT or MV must be adjusted for both systemic factors (blood pressure or age) and local ocular factors (AL and disc, cup, or ß-PPA area). Translational Relevance: Our results provided reference data on the LSFG measurement and are important in comparing ocular blood flow between individuals using LSFG.

One-Year Efficacy and Safety Assessment of Ripasudil, a Rho Kinase Inhibitor, in an Addition to or Replacing Existing Treatment Regimens: A Retrospective Study.

Purpose: To evaluate efficacy and safety of ripasudil for 1 year in addition to or replacing existing treatment regimens. Methods: We retrospectively reviewed the medical records for 128 eyes of 128 glaucoma patients who were prescribed ripasudil as an addition to or a switch from their preexisting antiglaucoma instillations. We investigated the rate and factors for discontinuation and intraocular pressure (IOP) reduction. Results: Almost half of the patients (60 eyes) discontinued ripasudil treatment before the 1 year mark, while remaining patients completed the treatment. The lack of efficacy and development of adverse effects were significantly correlated with discontinuation (P < 0.001) in the Cox proportional hazards model. In the Kaplan-Meier curve, adverse effects occurred in earlier phase and almost 60% dropped out within 3 months after ripasudil administration. However, adverse effects also occurred randomly throughout the study period. In patients who continued ripasudil, the mean IOPs (mmHg) at baseline, 6 and 12 months after treatment were 17.7 ± 5.1, 14.6 ± 5.0, and 14.8 ± 3.8 in the Addition group, and 17.8 ± 4.1, 15.4 ± 3.2, and 15.4 ± 5.0 in the Switch group, respectively (all P values <0.05). Conclusions: Almost half of the patients discontinued ripasudil owing to the lack of efficacy and the generation of adverse effects within the 1 year. In the remaining half, the addition and switching of ripasudil to the existing glaucoma treatment effectively reduced IOP for 1 year.

Factors Related to Superior and Inferior Hemifield Defects in Primary Open-Angle Glaucoma.

PURPOSE: We aimed to investigate factors related to superior and inferior hemifield defects in primary open-angle glaucoma (POAG). METHODS: Sixty-seven subjects with newly diagnosed, untreated POAG underwent optical coherence tomography (OCT) of the disc area, macular ganglion cell complex (mGCC), and circumpapillary retinal nerve fiber layer (cpRNFL) thickness within 6 months of the visual field (VF) test. Based on the VF and OCT results, 40 subjects had a superior and 27 an inferior hemifield defect. Clinical data including visual acuity, refractive error, disc hemorrhage, VF indexes, and medical history were recorded. RESULTS: Average mGCC thickness corresponding to the defective hemifields was thinner in the superior VF defect group than in the inferior VF defect group (P=0.003). Average total deviation (TD) was comparable between the two groups. However, the superior VF defect group had a higher prevalence of defects (P=0.001) and lower TD (P=0.002) within central 5 degrees of VF than the inferior VF defect group. In multivariate regression analyses, the temporal-lower and inferior-temporal cpRNFL thicknesses were significant contributing factors to the inferior mGCC thickness in the superior VF defect group. In the inferior VF defect group, the disc area, family history of glaucoma, and temporal-upper cpRNFL thickness contributed to the superior mGCC thickness. CONCLUSION: The inferior mGCC thickness corresponding to the superior hemifield defect group was significantly thinner than the superior mGCC thickness corresponding to the inferior hemifield defect group. The factors related to the reduction of the corresponding mGCC thickness may differ between superior VF defect and inferior VF defect groups.

Relationship between Macular Vessel Density and Focal Electroretinograms in Early Normal Tension Glaucoma.

Purpose: To evaluate the relationship between the macular vessel density and photopic negative response (PhNR) amplitude of focal electroretinograms (ERGs) in patients with early-stage normal tension glaucoma (NTG). Materials and Methods: This prospective cross-sectional study included a total of 42 subjects with early-stage NTG. Optical coherence tomography angiography was used to measure macular vessel density, and focal ERGs were elicited by a white light stimulus (30 cd/m2) with background light (1.5 cd/m2). The amplitude of the PhNR was measured from the peak of the b-wave to the PhNR trough. Mean visual field sensitivity was measured by the Humphrey Field Analyzer (HFA) program central 10-2. Spearman's coefficients were used to evaluate the correlation between the macular vessel density, PhNR amplitude, mean deviation (MD) of the HFA 10-2, retinal nerve fiber layer (RNFL) thickness, and ganglion cell complex (GCC) thickness measured by spectral domain-optical coherence tomography. Results: The mean MD of the HFA 10-2 was -2.0 ± 3.2 dB. The PhNR amplitude significantly correlated with the macular vessel density (r = 0.420, P = 0.006), but not with the MD, GCC thickness, or RNFL thickness. The macular vessel density significantly correlated with the MD (r = 0.364, P = 0.018) and RNFL thickness (r = 0.369, P = 0.016), but not with GCC thickness (r = 0.266, P = 0.089). Conclusions: Macular vessel density significantly correlated with PhNR amplitude in patients with early-stage NTG, suggesting that microvascular alterations are associated with functional changes recorded by focal ERG in very early-stage glaucoma.

Movement of retinal vessels toward the optic nerve head after increasing intraocular pressure in monkey eyes with experimental glaucoma.

A shift or displacement of the retinal blood vessels (RBVs) with neuroretinal rim thinning indicates the progression of glaucomatous optic neuropathy. In chronic open angle glaucoma, individuals with RBV positional shifts exhibit more rapid visual field loss than those without RBV shifts. The retinal vessels reportedly move onto the optic nerve head (ONH) in response to glaucoma damage, suggesting that RBVs are pulled toward the ONH in response to increased cupping. Whether this phenomenon only applies to RVBs located in the vicinity or inside the ONH or, more generally, to RBVs also located far from the ONH, however, is unclear. The aim of this study was to evaluate the movement of RBVs located relatively far from the ONH edge after increasing intraocular pressure (IOP) in an experimental monkey model of glaucoma. Fundus photographs were obtained in 17 monkeys. High IOP was induced in the monkeys by laser photocoagulation burns applied uniformly with 360° irradiation around the trabecular meshwork of the left eye. The right eye was left intact and used as a non-treated control. Considering the circadian rhythm of IOP, it was measured in both eyes of each animal at around the same time-points. Then, fundus photographs were obtained. Using Image J image analysis software, an examiner (N.E.) measured the fundus photographs at two time-points, i.e. before laser treatment (time 1) and the last fundus photography after IOP elevation (time 2). The following parameters were measured (in pixels): 1) vertical diameter of the ONH (DD), 2) distance from the ONH edge to the first bifurcation point of the superior branch of the central retinal vein (UV), 3) distance from the ONH edge to the first bifurcation point of the inferior branch of the central retinal vein (LV), 4) ONH area, and 5) surface area of the cup of the ONH. We calculated the ratios of UV to DD (UV/DD), LV to DD (LV/DD), and the cup area to disc area ratio (C/D). The mean UV/DD at time 1 (0.656 ± 0.233) was decreased at time 2 (0.542 ± 0.192) (p < 0.01), and the mean LV/DD at time 1 (0.642 ± 0.151) was decreased at time 2 (0.534 ± 0.171) (p < 0.01). The mean C/D at time 1 (0.303 ± 0.035) was increased at time 2 (0.556 ± 0.110) (p < 0.01). The mean IOP at time 1 was 19.8 ± 2.5 and that at time 2 was 54.2 ± 15.8. The amount and rate of the change in LV/DD and C/D between time 1 and time 2 were significantly correlated (r = -0.654 and -0.536, p = 0.004 and 0.026, respectively). Therefore, in an experimental monkey model of glaucoma, RBVs located relatively far from the ONH were pulled toward the ONH as cupping increased.

Association between Optic Nerve Head Microcirculation and Macular Ganglion Cell Complex Thickness in Eyes with Untreated Normal Tension Glaucoma and a Hemifield Defect.

Purpose. We evaluated the association between optic nerve head (ONH) microcirculation and macular ganglion cell complex (mGCC) thickness in patients with untreated normal tension glaucoma (NTG) and a hemifield defect. Methods. The medical records of 47 patients with untreated NTG were retrospectively reviewed. Laser speckle flowgraphy was used to obtain mean blur rate (MBR), a relative measure of blood flow. Average total deviation (TD), mGCC, and the circumpapillary retinal nerve fiber layer (cpRNFL) thickness were also analyzed. Results. All parameters corresponding to the defective hemifield were significantly lower than those corresponding to the normal hemifield. In the defective hemifield, MBR was correlated with TD, mGCC, and cpRNFL thickness. In the normal hemifield, MBR was only correlated with mGCC thickness, and multiple regression analysis showed that mGCC thickness was a significant contributing factor of the MBR. Conclusion. MBR was well correlated with mGCC thickness in eyes with untreated NTG and a hemifield defect. In the normal hemifield, mGCC thickness was a contributing factor of the MBR indicating that ONH circulatory dysfunction may be associated with retinal structural changes in the early stages of glaucoma. A reduction in ONH microcirculation may be an early indicator of the presence and progression of glaucoma.

Erratum to "Size of the Optic Nerve Head and Its Relationship with the Thickness of the Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Patients with Primary Open Angle Glaucoma".

[This corrects the article DOI: 10.1155/2015/186249.].

Size of the Optic Nerve Head and Its Relationship with the Thickness of the Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Patients with Primary Open Angle Glaucoma.

Purpose. To evaluate the relationships among the optic nerve head (ONH) area, macular ganglion cell complex (mGCC) thickness, circumpapillary retinal nerve fiber layer (cpRNFL) thickness, and visual field defects in patients with primary open angle glaucoma (POAG). Methods. This retrospective study included 90 eyes of 90 patients with POAG. The ONH area, rim area, mGCC thickness, and cpRNFL thickness were measured using optical coherence tomography. Mean deviation (MD) was measured using standard automated perimetry. The relationships among clinical factors including age, refraction, the ONH area, the rim area, the mGCC thickness, the cpRNFL thickness, and MD were evaluated using correlation coefficients and multiple regression analyses. Results. The significant correlation of the ONH area with refraction (r = 0.362, P < 0.001), the mGCC thickness (r = 0.225, P = 0.033), and the cpRNFL thickness (r = 0.253, P = 0.016) was found. Multiple regression analysis showed that the ONH area, rim area, and MD were selected as significant contributing factors to explain the mGCC thickness and cpRNFL thickness. No factor was selected to explain MD. Conclusions. The ONH area, in other words, the disc size itself may affect the mGCC thickness and cpRNFL thickness in POAG patients.

Baseline thickness of macular ganglion cell complex predicts progression of visual field loss.

BACKGROUND: Previous studies reported that the thickness of the macular ganglion cell complex (mGCC) showed good diagnostic ability for detecting glaucoma. However, its impact on the progression of visual field loss in primary open angle glaucoma (POAG) is unknown. The purpose of this study was to assess whether baseline mGCC thickness is associated with the progression of visual field loss in POAG. METHODS: Fifty-six patients with POAG were included in the study. All patients were followed for more than 2 years after baseline optical coherence tomography (OCT) measurements. They had at least five reliable Humphrey visual field tests with 30-2 Swedish Interactive Threshold Algorithm standard tests during the follow-up period. The subjects were divided into two groups according to the slope of the mean deviation (MD): the fast progression group (MD slope < -0.4 dB/y) and the slow progression group (MD slope ≥ -0.4 dB/y). Factors compared between the groups were as follows: age, baseline intraocular pressure (IOP), mean IOP during the follow-up, refraction, baseline MD, pattern standard deviation (PSD), and baseline OCT measurements. RESULTS: There were no significant differences between the two groups in age, baseline IOP, mean IOP during the follow-up, refraction, baseline MD or PSD, average thickness of retinal nerve fiber layer (RNFL), or disc parameters. However, the baseline mGCC thickness (average and inferior hemifield) was significantly thinner in the fast progression group than in the slow progression group (74.0 ± 7.2 µm vs. 80.3 ± 8.6 µm; 68.0 ± 6.6 µm vs. 78.2 ± 11.6 µm, respectively). Moreover, global loss volume and focal loss volume, which are parameters of mGCC, showed significantly higher rates in the fast progression group than in the slow progression group. In multivariate analysis, only mGCC thickness of the inferior hemifield was associated with disease progression (P = 0.007). CONCLUSIONS: Baseline mGCC thickness can be predictive of progressive visual field loss in patients with POAG.