Purpose.: To evaluate and compare the glaucoma discrimination ability of macular inner retinal layer (MIRL) thickness with that of peripapillary retinal nerve fiber layer (pRNFL) thickness measured by spectral-domain optical coherence tomography (RTVue-100; Optovue Inc, Fremont, CA) in patients with normal-tension glaucoma (NTG). Methods.: Sixty-five healthy subjects and 102 with NTG were enrolled. MIRL thickness provided by a ganglion cell complex (GCC) scan and two RNFL thicknesses measured by the NHM4 (RNFL1) and RNFL 3.45 (RNFL2) modes of the RTVue-100 system were analyzed. The areas under the receiver operating characteristic curves (AUCs) of MIRL and pRNFL thicknesses for discriminating patients with NTG from control subjects were determined. The AUCs were compared between patients with central visual field (VF) defects (VF; ≤10° of fixation) and peripheral VF defects (>10° from fixation). Results.: The average MIRL thickness showed a strong correlation with both RNFL1 and -2 thicknesses (R ² = 0.773, 0.774, both P < 0.0001). The AUCs for average MIRL, RNFL1, and RNFL2 thicknesses were not significantly different at 0.945, 0.973, and 0.976, respectively. However, the AUCs of the average and superior MIRL thicknesses were significantly less than that of the pRNFL thickness in eyes with moderate-to-advanced glaucoma and eyes with peripheral VF defects. Conclusions.: The average MIRL thickness showed a strong correlation with pRNFL thickness, because patients with NTG at an early stage showed paracentral VF defects near the fixation point. MIRL thickness showed glaucoma discrimination ability comparable to that of pRNFL thickness in patients with NTG with early VF defects. In eyes with advanced or peripheral VF defect, pRNFL measurement showed a better glaucoma diagnostic ability than did MIRL measurement.

Purpose. To investigate systemic and ocular hemodynamic risk factors for glaucomatous damage in eyes with normal tension glaucoma (NTG). methods. Each patient with diagnosed NTG underwent 24-hour monitoring of intraocular pressure (IOP) and blood pressure (BP), scanning laser polarimetry (GDx-VCC), and a Humphrey visual field (HVF) examination. Multivariate regression models were used to evaluate potential risk factors: age, spherical equivalent, central corneal thickness (CCT), mean/peak in-hospital IOP, circadian IOP fluctuation, average mean arterial pressure (MAP), circadian MAP fluctuation, and circadian fluctuation of mean ocular perfusion pressure (MOPP). Functional outcome variables for glaucomatous damage were mean deviation (MD), pattern SD (PSD), and Advanced Glaucoma Intervention Study (AGIS) score. Anatomic outcome variables were TSNIT (temporal, superior, nasal, inferior, and temporal) average, superior average, inferior average, and nerve fiber indicator (NFI) on GDx-VCC. results. One hundred thirteen eyes of 113 patients met the inclusion criteria. In the multivariate regression models, larger circadian MOPP fluctuation was significantly associated with decreased MD, increased PSD, and increased AGIS score among functional outcome variables and with reduced TSNIT average, reduced inferior average, and increased NFI among anatomic outcome variables. Larger MAP fluctuation was associated with decreased MD, increased PSD, reduced TSNIT average, reduced inferior average, and increased NFI. CCT was not associated with any outcome variable. conclusions. Of the functional and anatomic outcome variables, circadian MOPP fluctuation was the most consistent clinical risk factor for glaucoma severity in eyes with NTG. This finding may suggest an etiology of NTG as a chronic ischemic end organ disease.

The new term Flammer syndrome describes a phenotype characterized by the presence of primary vascular dysregulation together with a cluster of symptoms and signs that may occur in healthy people as well as people with disease. Typically, the blood vessels of the subjects with Flammer syndrome react differently to a number of stimuli, such as cold and physical or emotional stress. Nearly all organs, particularly the eye, can be involved. Although the syndrome has some advantages, such as protection against the development of atherosclerosis, Flammer syndrome also contributes to certain diseases, such as normal tension glaucoma. The syndrome occurs more often in women than in men, in slender people than in obese subjects, in people with indoor rather than outdoor jobs, and in academics than in blue collar workers. Affected subjects tend to have cold extremities, low blood pressure, prolonged sleep onset time, shifted circadian rhythm, reduced feeling of thirst, altered drug sensitivity, and increased general sensitivity, including pain sensitivity. The plasma level of endothelin-1 is slightly increased, and the gene expression in lymphocytes is changed. In the eye, the retinal vessels are stiffer and their spatial variability larger; the autoregulation of ocular blood flow is decreased. Glaucoma patients with Flammer syndrome have an increased frequency of the following: optic disc hemorrhages, activated retinal astrocytes, elevated retinal venous pressure, optic nerve compartmentalization, fluctuating diffuse visual field defects, and elevated oxidative stress. Further research should lead to a more concise definition, a precise diagnosis, and tools for recognizing people at risk. This may ultimately lead to more efficient and more personalized treatment.

Purpose. To study blood pressure (BP), intraocular pressure (IOP), and mean ocular perfusion pressure (MOPP) in patients with untreated normal tension glaucoma (NTG), and to investigate the relationship between circadian MOPP fluctuation and visual field status at initial presentation. methods. IOP and BP were evaluated in hospital over 24 hours in 132 patients with NTG, with measurements taken every 2 hours between 12 PM and 10 AM the following day, except for the period between 12 and 6 AM, during which measurements were taken every 3 hours. MOPP was calculated from the 24-hour IOP and BP data. Patients were classified into three groups—nondippers, dippers, and overdippers—corresponding to the degree of reduction in their nocturnal mean arterial pressure (MAP) compared with their diurnal MAP. IOP and systemic and ocular hemodynamic parameters were compared among the groups. The correlations between circadian MOPP fluctuation and visual field scores (mean deviation [MD] and corrected pattern standard deviation [CPSD]) at initial presentation were analyzed. results. Forty-one (31.1%) of the patients with NTGs were classified into the nondipper group, 36 (27.2%) into the dipper group, and 55 (41.7%) into the overdipper group. Marked circadian MOPP fluctuation was noted in the overdipper group (P < 0.05). Circadian MOPP fluctuation showed positive associations with visual field indices at initial diagnosis of NTG (P < 0.05, R ² = 0.056 with MD, R ² = 0.038 with CPSD). conclusions. Marked circadian MOPP fluctuation was associated with nocturnal BP reduction. Circadian MOPP fluctuation may be a risk factor for the development of NTG.

Purpose.: To investigate the relationship between clinical factors including 24-hour mean ocular perfusion pressure (MOPP, ⅔ × mean arterial pressure [MAP] − intraocular pressure [IOP]) and visual field (VF) progression in eyes with medically treated normal-tension glaucoma (NTG). Methods.: One hundred one eyes of 101 NTG patients followed up for more than 4 years (mean follow-up, 6.2 years ± 12.1 months) were included after retrospective chart review. Several clinical factors including demographic, systemic, ocular risk factors, and 24-hour MOPP were explored for associations with decreasing VF. Kaplan-Meier analyses were performed to compare outcomes with reference to four risk factors (age, myopia, and elevated MAP and MOPP fluctuation) for VF deterioration. Hazard ratios (HRs) for the association between potential risk factors and glaucoma progression were obtained using Cox proportional hazards models. Results.: Overall VF progression was detected in 29 (28.7%) eyes. There were significant differences between progressors and nonprogressors in nocturnal MAP and MOPP fluctuations (both P < 0.0001), 24-hour MAP, and MOPP fluctuations (both P < 0.0001), initial mean deviation (P = 0.0034), and pattern standard deviation (PSD) score (P < 0.0001). Both elevated 24-hour MAP and MOPP fluctuations were associated with greater VF progression probabilities based on Kaplan-Meier analyses. Among all risk factors investigated, the Cox proportional hazards model indicated that VF progression was significantly associated with 24-hour MOPP fluctuation and initial PSD score. Conclusions.: Clinical factors other than IOP were associated with VF progression in our series of medically treated NTG eyes. Twenty-four-hour MOPP fluctuation was the most consistent prognostic factor for glaucoma progression.

The study aimed to evaluate the quantitative characteristics of the macular vessel density (VD) and foveal avascular zone (FAZ) in glaucoma using optical coherence tomography angiography (OCT-A). Cross-sectional, age- and sex-matched case–control study. Fifty-two eyes of 52 patients with primary open angle glaucoma and 52 eyes from 52 healthy participants were recruited retrospectively. OCT-A was performed on a 3 x 3-mm macular region centered on the fovea. OCT-A scans were manually graded to define the FAZ. Parafoveal VD in superficial and deep retina were analyzed in the circular- and quadrant-segmented zone. The FAZ parameters included size, perimeter, and circularity index. The regression analysis among VD and FAZ-related parameters and ocular parameters was performed, and the diagnostic ability was calculated with refractive error adjusted. For both groups, the mean age and the sex ratio was not different between groups. With refractive error adjusted, the average macular VD was lower in glaucoma than in the control group for superficial (P = 0.013), deep (P<0.001), and the whole retina (P = 0.002). There were increased FAZ perimeter and decreased FAZ circularity index in glaucoma when compared with controls (P<0.001). In the multivariate regression models, FAZ circularity index were significantly associated with decreased peripapillary RNFL thickness (P = 0.007) and macular GCIPL thickness (P = 0.009) measured by OCT. The refractive-error adjusted area under receiver operating characteristics was highest for FAZ circularity index (0.905; 95% CI, 0.844–0.966), followed by temporal deep retinal VD (0.870; 95% CI, 0.803–0.937) and FAZ perimeter (0.858; 95% CI, 0.784–0.932). Decreased macular VD, increased FAZ perimeter, and decreased FAZ circularity index were observed in eyes with glaucoma using OCT-A. With refractive error adjusted, these parameters showed considerable diagnostic value for glaucoma. FAZ circularity index may be a novel biomarker representing disruption of the parafoveal capillary network in glaucoma, as supported by its association with structural parameters.