Long-term reproducibility of optical coherence tomography angiography in healthy and stable glaucomatous eyes.

BACKGROUND/AIMS: To assess and compare long-term reproducibility of optic nerve head (ONH) and macula optical coherence tomography angiography (OCTA) vascular parameters and optical coherence tomography (OCT) thickness parameters in stable primary open-angle glaucoma (POAG), glaucoma suspect and healthy eyes. METHODS: Eighty-eight eyes (15 healthy, 38 glaucoma suspect and 35 non-progressing POAG) of 68 subjects who had at least three visits within 1-1.5 years with OCTA and OCT imaging (Angiovue; Optovue, Fremont, California, USA) on the same day were included. A series of vascular and thickness parameters were measured including macular parafoveal vessel density (pfVD), ONH circumpapillary capillary density (cpCD), macular parafoveal ganglion cell complex (pfGCC) and ONH circumpapillary retinal nerve fibre layer (cpRNFL). A random effects analysis of variance model was used to estimate intraclass correlation (ICC) coefficients and long-term variability estimates. RESULTS: ICC was lower for OCTA (pfVD 0.823 (95% CI 0.736 to 0.888) and cpCD 0.871 (0.818 to 0.912)) compared with OCT (pfGCC 0.995 (0.993 to 0.997) and cpRNFL 0.975 (0.964 to 0.984)). Within-subject test-retest SD was 1.17% and 1.22% for pfVD and cpCD, and 0.57 and 1.22 µm for pfGCC and cpRNFL. Older age and lower signal strength index were associated with decreasing long-term variability of vessel densities. CONCLUSIONS: OCTA-measured macula and ONH vascular parameters have good long-term reproducibility, supporting the use of this instrument for longitudinal analysis. OCTA long-term reproducibility is less than OCT-measured thickness reproducibility. This needs to be taken into consideration when serial OCTA images are evaluated for change. TRIAL REGISTRATION NUMBER: NCT00221897.

Central macular OCTA parameters in glaucoma.

BACKGROUND/AIMS: To investigate the relationship between the foveal avascular zone (FAZ) parameters assessed by optical coherence tomography angiography (OCTA) and central visual field parameters in glaucoma and healthy subjects. METHODS: One hundred and eighty-eight subjects (248 eyes), including 24 healthy (38 eyes), 37 glaucoma suspect (42 eyes, and 127 primary open angle glaucoma (POAG) patients (168 eyes), underwent imaging using OCTA and standard automated perimetry using the 24-2 and 10-2 Swedish Interactive Thresholding Algorithm. OCTA-based and OCT-based FAZ parameters (superficial FAZ area, FAZ circumference), foveal vessel density (FD300) and foveal thickness were measured. The correlation between FAZ parameters and visual field parameters was assessed using linear mixed model. RESULTS: Axial length adjusted-FAZ area was not different among the three groups (mean (95% CI)): in healthy 0.31 (0.27 to 0.36) mm2, glaucoma suspect 0.29 (0.26 to 0.31) mm2 and POAG eyes 0.28 (0.27 to 0.30) mm2 (p=0.578). FD300 was lower in glaucoma suspect 49.1% (47.9% to 50.4%) and POAG eyes 48.7% (48.1% to 49.4%) than healthy eyes 50.5% (49.3% to 51.7%) though the difference was not statistically significant (p=0.071). Lower FD300 was associated with worse 24-2 and 10-2 visual field mean deviation and foveal threshold in multivariable linear mixed models (all p<0.05). In addition, a smaller FAZ area was associated with lower intraocular pressure (IOP) (p=0.026). CONCLUSIONS: The FD300, but not the FAZ area was correlated with 10° central visual field mean deviation and foveal threshold in healthy, glaucoma suspect and POAG eyes. In contrast, a smaller FAZ area was associated with lower IOP.

Rates of Circumpapillary Retinal Nerve Fiber Layer Thinning and Capillary Density Loss in Glaucomatous Eyes with Disc Hemorrhage.

PURPOSE: To investigate longitudinal changes in rates of optic nerve head circumpapillary retinal nerve fiber layer (cpRNFL) thinning and vessel density loss in patients with primary open-angle glaucoma with or without a history of disc hemorrhage (DH). DESIGN: Observational cohort. METHODS: In this longitudinal study, 34 eyes with DH and 134 eyes without DH that had ≥1.5 years of follow-up and 3 optical coherence tomography and optical coherence tomography angiography follow-up scans were enrolled. A linear mixed-effects model was used to compare the rates of cpRNFL thinning and vessel density loss between DH and non-DH eyes. RESULTS: Rates of whole image capillary density loss were faster in the DH group compared with the non-DH group (mean difference [95% confidence interval] -0.32% [-0.59% to -0.04%] per year; P = .027). Faster mean rates of vessel density loss were found in the inferotemporal, inferonasal, and nasal sectors in eyes with DH than without DH (P < .05). There was no statistically significant difference in the global rate of cpRNFL thinning between the 2 groups (P = .679). The mean rate of cpRNFL thinning was faster in the DH group compared with the non-DH group only in the inferotemporal sector (mean difference [95% confidence interval] -1.01 µm (-1.62 µm to -0.40 µm) per year; P = .001). CONCLUSIONS: Mean rates of vessel density loss between DH and non-DH eyes were different not only in the affected area but also in the other regions. In contrast, a significant difference in cpRNFL thinning between the 2 groups was detected only in the inferotemporal sector. Disc hemorrhage is an independent predictor of faster vessel density loss in glaucoma suspects and patients with primary open-angle glaucoma.

Optic Nerve Engraftment of Neural Stem Cells.

Purpose: To evaluate the integrative potential of neural stem cells (NSCs) with the visual system and characterize effects on the survival and axonal regeneration of axotomized retinal ganglion cells (RGCs). Methods: For in vitro studies, primary, postnatal rat RGCs were directly cocultured with human NSCs or cultured in NSC-conditioned media before their survival and neurite outgrowth were assessed. For in vivo studies, human NSCs were transplanted into the transected rat optic nerve, and immunohistology of the retina and optic nerve was performed to evaluate RGC survival, RGC axon regeneration, and NSC integration with the injured visual system. Results: Increased neurite outgrowth was observed in RGCs directly cocultured with NSCs. NSC-conditioned media demonstrated a dose-dependent effect on RGC survival and neurite outgrowth in culture. NSCs grafted into the lesioned optic nerve modestly improved RGC survival following an optic nerve transection (593 ± 164 RGCs/mm2 vs. 199 ± 58 RGCs/mm2; P < 0.01). Additionally, RGC axonal regeneration following an optic nerve transection was modestly enhanced by NSCs transplanted at the lesion site (61.6 ± 8.5 axons vs. 40.3 ± 9.1 axons, P < 0.05). Transplanted NSCs also differentiated into neurons, received synaptic inputs from regenerating RGC axons, and extended axons along the transected optic nerve to incorporate with the visual system. Conclusions: Human NSCs promote the modest survival and axonal regeneration of axotomized RGCs that is partially mediated by diffusible NSC-derived factors. Additionally, NSCs integrate with the injured optic nerve and have the potential to form neuronal relays to restore retinofugal connections.

Characteristics of Central Visual Field Progression in Eyes with Optic Disc Hemorrhage.

PURPOSE: To investigate the characteristics and rate of central visual field loss after optic disc hemorrhage (DH). DESIGN: Prospective cohort study. METHODS: Three hundred forty-three eyes of 220 subjects who had ≥3 years of follow-up with a minimum of 5 visits with 10-2 and 24-2 visual field (VF) were recruited. Rates of 10-2 mean deviation (MD) loss in each hemifield and predefined zones were compared using linear mixed-effects models in DH and non-DH eyes. Clustered pointwise regression analysis was also used to define central VF progressors and compared with 24-2 VF loss using guided progression analysis. RESULTS: Thirty-nine eyes with DH and 304 eyes without DH had a mean follow-up of 5.2 years. Eyes with DH had rates of 10-2 MD loss that were 3 times faster than non-DH eyes (mean difference -0.36 dB/year [95% confidence interval 0.54-0.18]; P < .001) and were 3.7 times more likely to progress (P = .002). A larger proportion of glaucomatous eyes showed central VF progression rather than peripheral VF progression in the DH group (30.8% vs. 20.5%) compared with the non-DH group (10.9% vs. 9.2%). In early glaucoma, the rate of 10-2 MD loss was 5.5 times faster in DH eyes than in non-DH eyes (P < .001). Superonasal and superotemporal central VF regions progressed more rapidly than other regions, especially in DH eyes. CONCLUSION: Central VF loss is accelerated in glaucoma eyes with DH and it corresponds topographically to the DH location. In patients with glaucoma with DH, one should consider supplementing 10-2 VFs with 24-2 VFS to monitor the disease.

Rates of Retinal Nerve Fiber Layer Thinning in Distinct Glaucomatous Optic Disc Phenotypes in Early Glaucoma.

PURPOSE: To compare spectral-domain optical coherence tomography (SDOCT) measured circumpapillary retinal nerve fiber layer (cpRNFL) among 4 glaucomatous optic disc phenotypes in early glaucoma. DESIGN: Clinical cohort study METHODS: In this study, 218 early glaucoma eyes that had at least 3 years of follow-up and a minimum of 4 SDOCT scans were recruited. The optic discs were classified into 4 types based on appearance: 76 generalized cup enlargement (GE), 53 focal ischemic (FI), 22 myopic glaucomatous (MY), and 67 senile sclerotic (SS). A linear mixed effects model was used to compare the rates of global and regional cpRNFL thinning among optic disc phenotypes. RESULTS: After adjusting for confounders, the SS group (mean [95% CI]: -1.01 [-1.30, -0.73] µm/y) had the fastest mean rate of global cpRNFL thinning followed by FI (-0.77 [-0.97, -0.57] µm/y), MY (0.59 [-0.81, -0.36] µm/y), and GE (-0.58 [-0.75, -0.40] µm/y) at P < .001. The inferior temporal sector had the fastest rate of cpRNFL thinning among the regional measurements except for the MY group (-0.68 [-1.10, -0.26] µm/y, P = .002). In the multivariable analysis, GE (P = .002) and MY (P = .010) phenotypes were associated with significantly slower global rates of cpRNFL thinning compared with the SS phenotype. CONCLUSIONS: Rates of cpRNFL thinning were different among the 4 glaucomatous optic disc phenotypes. Those patients with early glaucoma with SS phenotype have the fastest cpRNFL thinning. These patients may benefit from more frequent monitoring and the need to advance therapy if cpRNFL thinning is detected.