Multi-Quantitative Assessment of AS-OCTA Complemented AS-OCT for Monitoring Filtering Bleb Function After Trabeculectomy.

Purpose: The purpose of this study was to explore a quantitative grading system of the filtering bleb combined anterior segment optical coherence tomography angiography (AS-OCTA) vascular features and optical coherence tomography (OCT) morphological features. Methods: One hundred three eyes of 103 patients diagnosed with primary open-angle glaucoma and undergone trabeculectomy over 6 months were divided into success and failure groups according to postoperative intraocular pressure (IOP) level. Vessel density (VD) and vessel diameter index (VDI) were examined by AS-OCTA. Bleb's morphology, including bleb height (BH), and microcyst-structure (MCS) were detected by AS-OCT. Multi-vascular model score (MVMS) was calculated by comprehensive factor analysis, and the comprehensive grading system (MVMS-MCS-BH) was analyzed by linear regression. The efficiency our method was verified by receiver operating characteristic (ROC) analysis. Results: The VD and VDI were higher in the failure group and closely related to post-trabeculectomy IOP (all P = 0.000). The MVMS was mostly consisted of VD in all regions, and VDIs of nasal, central, and temporal positions in sequence. MVMS ≥0, BH <1.33, and non-MCS were significantly associated with IOP increasing (coefficient = -3.23, -3.69, and 8.10, all P = 0.000). MVMS-BH-MCS got a higher area under curve (AUC), sensitivity, and specificity (0.92, 100%, and 80.30%) than the slit-lamp method (0.62, 72.20%, and 46.43%, respectively). Conclusions: The quantitative vascular characteristics detected by AS-OCTA were significant for the bleb monitor. The MVMS-BH-MCS grading system had achieved outstanding accuracy in reflecting the surgical results. Translational Relevance: The multi-vascular biomarker and comprehensive evaluation combined vascular and morphological parameters yield useful information on surgical outcomes, and help ophthalmologists to monitor patients effectively.

Correlation between spherical equivalent and biometry parameters in adult Cynomolgus macaque.

PURPOSE: To characterize the distribution of refractive and ocular biometry parameters and analyze the effect factors of the refractive status in cynomolgus monkey colonies. METHODS: A Population-based cross-sectional study was conducted in adult cynomolgus macaque colonies. Animals were anesthetized with Zoletil 50. Intraocular pressure was measured using the Icare tonometer. Cycloplegic refraction (three drops of 1% tropicamide) and corneal radius of curvature (CRC) were measured using an autorefractor. The spherical equivalent (SE) was calculated. Biometric measurements, including the anterior chamber depth (ACD), lens thickness (LT), and axial length (AL), were obtained by A-scan ultrasonography. The AL-to-CR ratio (AL/CRC) was calculated. Central corneal thickness (CCT) and choroidal thickness (ChT) were measured using the Heidelberg Spectralis HRA OCT. Multiple regression analysis was performed to explore the association between refraction and ocular biometry. RESULTS: Among 263 cynomolgus monkeys (aged 5-26 years), which consisted of 520 eyes, 29.42% had hyperopia, 27.12% had emmetropia, 33.27% had mild-to-moderate myopia and 10.19% had high myopia. The mean SE was -1.27 ± 3.44 Diopters (D). The mean CRC, CCT, AL, and ChT was 5.70 ± 0.22 mm, 454.30 ± 32.40 µm, 18.76 ± 0.89 mm and 188.96 ± 38.19 µm, respectively. The LT was the thickest in the hyperopic eyes. CRC was the lowest, and CCT was the thickest in high myopic eyes. AL increased, while ChT decreased as SE decreased. For the SE variance, AL alone explained 40.5%; age, AL, and CRC together explained 57.5%. CONCLUSIONS: The refractive characteristics and biometry parameters of cynomolgus monkeys are highly comparable to those of humans. AL, CRC, and ChT showed the similar variation tendency in cynomolguses when compared to humans. Cynomolgus monkeys with naturally-occurring refractive errors may be a good animal model for refractive studies.

Selective deletion of zinc transporter 3 in amacrine cells promotes retinal ganglion cell survival and optic nerve regeneration after injury.

Vision depends on accurate signal conduction from the retina to the brain through the optic nerve, an important part of the central nervous system that consists of bundles of axons originating from retinal ganglion cells. The mammalian optic nerve, an important part of the central nervous system, cannot regenerate once it is injured, leading to permanent vision loss. To date, there is no clinical treatment that can regenerate the optic nerve and restore vision. Our previous study found that the mobile zinc (Zn2+) level increased rapidly after optic nerve injury in the retina, specifically in the vesicles of the inner plexiform layer. Furthermore, chelating Zn2+ significantly promoted axonal regeneration with a long-term effect. In this study, we conditionally knocked out zinc transporter 3 (ZnT3) in amacrine cells or retinal ganglion cells to construct two transgenic mouse lines (VGATCreZnT3fl/fl and VGLUT2CreZnT3fl/fl, respectively). We obtained direct evidence that the rapidly increased mobile Zn2+ in response to injury was from amacrine cells. We also found that selective deletion of ZnT3 in amacrine cells promoted retinal ganglion cell survival and axonal regeneration after optic nerve crush injury, improved retinal ganglion cell function, and promoted vision recovery. Sequencing analysis of reginal ganglion cells revealed that inhibiting the release of presynaptic Zn2+ affected the transcription of key genes related to the survival of retinal ganglion cells in postsynaptic neurons, regulated the synaptic connection between amacrine cells and retinal ganglion cells, and affected the fate of retinal ganglion cells. These results suggest that amacrine cells release Zn2+ to trigger transcriptomic changes related to neuronal growth and survival in reginal ganglion cells, thereby influencing the synaptic plasticity of retinal networks. These results make the theory of zinc-dependent retinal ganglion cell death more accurate and complete and provide new insights into the complex interactions between retinal cell networks.

Development and validation of the 40-item Glaucoma Visual Functioning Questionnaire.

AIMS: To evaluate the psychometric properties of a newly designed questionnaire, the 40-item Glaucoma Visual Functioning Questionnaire (GVFQ-40), in a Chinese sample to capture the visual ability of patients with glaucomatous vision impairment in five domains. METHODS: Eighty-four glaucoma suspects (controls) and 270 glaucoma patients were recruited from the Glaucoma Clinic at Zhongshan Ophthalmic Centre in this cross-sectional, observational study. All subjects completed two questionnaires during routine clinical visits: the GVFQ-40 and the validated National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25). The discriminant, criterion-related and construct validity of the GVFQ-40 were assessed. A subset of subjects completed the GVFQ-40 twice, with an interval of 7-21 days, to determine test-retest reliability. RESULTS: Domain-specific and total GVFQ-40 scores were significantly higher (worse visual ability) in glaucoma patients than in controls (all p<0.001). All pairwise subgroup comparisons were statistically significant except for the 'mobility' domain comparison between the mild visual field loss and control groups (p=0.189). Significant differences between these two groups were observed in only 2 of the 12 dimensions on the NEI VFQ-25. The GVFQ-40 results demonstrated strong correlations with better-eye mean deviation and Visual Field Index (glaucoma severity measures). Exploratory factor analysis tended to confirm a three-domain structure. Test-retest intraclass correlation coefficients were higher than 0.927 for domain-specific and total GVFQ-40 scores. CONCLUSIONS: The GVFQ-40 possesses good validity and reliability. It can be used to evaluate the impact of glaucomatous damage on visual ability and has potential in the evaluation of intervention efficacy. TRIAL REGISTRATION NUMBER: NCT04722861.

Increased Mobile Zinc Regulates Retinal Ganglion Cell Survival via Activating Mitochondrial OMA1 and Integrated Stress Response.

Retinal ganglion cells (RGCs), the projection neurons of the eye, are irreversibly lost once the optic nerve is injured, which is a critical mechanism of glaucoma. Mobile zinc (Zn2+) levels rapidly increase in retinal interneuron amacrine cells and Zn2+ is then transferred to RGCs via the Zn2+ transporter protein ZnT-3, triggering RGC loss in optic nerve injury. Zn2+ chelation and ZnT-3 deletion promote long-term RGC survival. However, the downstream signaling pathways of Zn2+ in RGCs remains unknown. Here, we show that increased levels of Zn2+ upregulate the expression and activity of mitochondrial zinc metallopeptidase OMA1 in the retina, leading to the cleavage of DELE1 and activation of cytosolic eIF2α kinase PKR, triggering the integrated stress response (ISR) in RGCs. Our study identified OMA1 and ISR as the downstream molecular mechanisms of retinal Zn2+ and potential targets for preventing the progression of Zn2+-associated neuronal damage.

Characteristic Assessment of Angiographies at Different Depths with AS-OCTA: Implication for Functions of Post-Trabeculectomy Filtering Bleb.

This study aimed to analyze the quantitative vascular biomarkers of filtering bleb function at different depths using anterior segment optical coherence tomography angiography (AS-OCTA). This cross-sectional study is registered on Clinicaltrails.gov (NCT04515017). Forty-six eyes with primary open-angle glaucoma that had undergone trabeculectomy with mitomycin-C for more than six months were included. Vessel density (VD) and vessel diameter index (VDI) in the superficial layer (SL), Tenon's layer (TL), and deep layer (DL) of the bleb were obtained. The VD and VDI were higher in the failure group (both p = 0.000). Significant correlations were found between the SL, TL, DL's VDI, and IOP in the success group (p = 0.013, 0.016, 0.031, respectively). The VD of the TL and DL were related to IOP in the failure group (p = 0.012, 0.009). Tenon's VD (TVD) and Tenon's VDI (TVDI) correlated with IOP adjusting for TVD, TVDI, and the Indiana Bleb Appearance Grading Scale (IBAGS) (p = 0.009, 0.043) or Kenfeld grading system (KGS) (p = 0.011, 0.016). The area under curve (AUC) of the TVD, TVDI, IBAGS, and KGS to predict surgery failure were 0.960, 0.925, 0.770, and 0.850. AS-OCTA realized the quantitative evaluation of vessels, especially the invisible vascularity beneath the conjunctiva. TVD and TVDI as detected by AS-OCTA better reflected bleb function than conventional grading systems.