ObjectivesTo evaluate the vascular architecture of the radial peripapillary capillaries (RPCs) and its relation with visual function in patients with open-angle glaucoma (OAG) and normal-tension glaucoma using spectral-domain optical coherence tomography (SD-OCT) angiography.Subjects and methodsClear OCT angiography images of blood vessels in the optic disc and peripapillary retina were obtained from 52 patients (52 eyes) aged 55.42±10.64 (range 28–72) years with primary OAG. The mean spherical equivalent was -3.19±2.31 diopters, and the mean deviation (MD) of the central 24/30-2 threshold test using the Humphrey Field Analyzer (HFA) was -10.47±7.99 dB. The correlations between the disappearance angle of the RPCs on OTC images, flow density (FD) and the circumpapillary retinal nerve fiber layer (cpRNFL) thickness, the angle of retinal nerve fiber layer (RNFL) defect, the MD and pattern standard deviation (PSD) values of the HFA central 24/30-2 threshold test using the Swedish interactive thresholding algorithm, the sensitivity threshold, age, corneal thickness, and refractive value were analyzed. In addition, the correlation between FD and the cpRNFL thickness was analyzed at FD measurement points.ResultsFD was significantly correlated with cpRNFL thickness, PSD value, MD value, and sensitivity threshold, whereas the disappearance angle of the RPCs was significantly correlated with the angle of the RNFL defect (P<0.001), MD value (P<0.01), and sensitivity threshold (P<0.01). There was a negative correlation between FD and age (P<0.05). The Pearson correlation coefficient of FD and cpRNFL thickness in the area surrounding the optic disc revealed the most significant correlation in the inferior visual field (r = 0.851, P<0.001), followed by the superior visual field (r = 0.803, P<0.001) and then the temporal visual field (r = 0.653, P<0.001).ConclusionSD-OCT angiography enabled thorough observation of the RPCs. FD and the disappearance angle of the RPCs were significantly and independently correlated with glaucoma-related functional and morphological changes in the optic nerve, suggesting that these two factors are novel functional and morphological indicators of visual defects due to glaucoma.
To estimate the central 10-degree visual field of glaucoma patients using en-face images obtained by optical coherence tomography (OCT), and to examine its usefulness. Patients and methods Thirty-eight eyes of 38 patients with primary open angle glaucoma were examined. En-face images were obtained by swept-source OCT (SS-OCT). Nerve fiber bundles (NFBs) on enface images at points corresponding to Humphrey Field Analyzer (HFA) 10-2 locations were identified with retinal ganglion cell displacement. Estimated visual fields were created based on the presence/absence of NFBs and compared to actual HFA10-2 data. κ coefficients were calculated between probability plots of visual fields and NFBs in en-face images. Results Actual HFA10-2 data and estimated visual fields based on en-face images were well matched: when the test points of <5%, <2%, and <1% of the probability plot in total deviation (TD) and pattern deviation (PD) of HFA were defined as points with visual field defects, the κ coefficients were 0.58, 0.64, and 0.66 in TD, respectively, and 0.68, 0.69, and 0.67 in PD. In eyes with spherical equivalent � −6 diopters, κ coefficients for <5%, <2%, and <1% were 0.58, 0.62, and 0.63 in TD and 0.66, 0.67, and 0.65 in PD, whereas for the myopic group with spherical equivalent < −6 diopters, the values were 0.58, 0.69, and 0.71 in TD and 0.72, 0.71, and 0.71 in PD, respectively. There was no statistically significant difference in κ coefficients between highly myopic eyes and eyes that were not highly myopic. Conclusions NFB defects in en-face images were correlated with HFA10-2 data. Using en-face images obtained by OCT, the central 10-degree visual field was estimated, and a high degree of concordance with actual HFA10-2 data was obtained. This method may be useful for detecting functional abnormalities based on structural abnormalities.
Mitophagy plays an important role in the maintenance of mitochondrial homeostasis. PTEN-induced kinase (PINK1), a key regulator of mitophagy, is degraded constitutively under steady-state conditions. During mitophagy, it becomes stabilized in the outer mitochondrial membrane, particularly under mitochondrial stress conditions, such as in treatment with uncouplers, generation of excessive mitochondrial reactive oxygen species, and formation of protein aggregates in mitochondria. Stabilized PINK1 recruits and activates E3 ligases, such as Parkin and mitochondrial ubiquitin ligase (MUL1), to ubiquitinate mitochondrial proteins and induce ubiquitin-mediated mitophagy. Here, we found that the anticancer drug gemcitabine induces the stabilization of PINK1 and subsequent mitophagy, even in the absence of Parkin. We also found that gemcitabine-induced stabilization of PINK1 was not accompanied by mitochondrial depolarization. Interestingly, the stabilization of PINK1 was mediated by MUL1. These results suggest that gemcitabine induces mitophagy through MUL1-mediated stabilization of PINK1 on the mitochondrial membrane independently of mitochondrial depolarization.
Precis: The foveal avascular zone (FAZ) in optical coherence tomography angiography is significantly correlated with retinal inner layer thickness, Humphrey field analyzer (HFA) 10-2 sensitivity threshold, and mean deviation (MD) value in open-angle glaucoma patients. Purpose: The purpose of this study was to measure the FAZ area using optical coherence tomography angiography and investigate its relationship with retinal inner layer thickness and visual field defects in eyes with open-angle glaucoma. Participants and Methods: A total of 52 eyes with open-angle glaucoma from 52 patients. FAZ area was measured using optical coherence tomography angiography in angio-macula mode. Thicknesses of retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCL+IPL), and ganglion cell complex (GCC) were determined using a 7 mm×7 mm macular (V) map via 3D-OCT. Correlations of FAZ area with sensitivity threshold measurements, foveal threshold (FT), and MD value in the HFA10-2 visual field were analyzed for each inner retinal layer. Results: FAZ area was 0.26±0.07 mm2; overall mean thicknesses were 19.14±6.55 μm (RNFL), 57.34±5.93 µm (GCL+IPL), and 75.87±10.96 μm (GCC); mean FT was 35.23±3.15 dB, and sensitivity threshold was 20.81±7.22 dB in the HFA10-2 visual field. FAZ area was significantly correlated with the thickness of individual retinal layers in the entire field (RNFL, P<0.001; GCL+IPL, P<0.001; GCC, P<0.001), sensitivity threshold (P=0.01), FT (P<0.001), and MD value (P=0.011). Conclusion: FAZ area was significantly negatively correlated with retinal inner layer thickness, sensitivity threshold, FT, and MD value in the HFA10-2 visual field.
Purpose. To evaluate the effect on intraocular pressure (IOP) of switching from latanoprost and travoprost monotherapy to timolol fixed combinations in Japanese patients with normal-tension glaucoma (NTG). Methods. 27 NTG patients (54 eyes) were compared IOP, superficial punctuate keratitis (SPK) scores, and conjunctival injection scores in eyes treated with prostaglandin (PG) or PG analog/beta-blocker (PG/b) fixed-combination 6 months after the change in therapy. Results. The mean baseline intraocular pressure was 17.4 ± 1.59 mmHg in eyes receiving PG therapy only and 17.4 ± 1.69 mmHg in eyes switched to PG/b. Switching to fixed combination therapy from PG monotherapy, the mean IOP was 13.1 ± 1.79 mmHg (P < 0.001) (−24.71% reduction from baseline) at 6 months. The mean conjunctival injection score was 0.69 for eyes on PG monotherapy and 0.56 for eyes on fixed combination therapy (P = 0.028). The mean SPK scores were 0.46 and 0.53. This difference was not statistically significant (P = 0.463). Conclusions. Switching from PG monotherapy to PG/b fixed combination therapy for NTG resulted in a greater intraocular pressure reduction than PG alone without increasing the number of instillations.
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