Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

Trend of glaucoma internal filtration surgeries in a tertiary hospital in China.

AIM: To evaluate the trend of glaucoma internal filtration surgeries for inpatients between 2015 and 2021 at the Eye Hospital of Wenzhou Medical University. METHODS: A review of the medical records of inpatients who had been diagnosed with glaucoma and received anti-glaucoma surgery between January 1, 2015 and December 31, 2021 was conducted. The glaucoma diagnosis in this study included primary open angle glaucoma, primary angle-closure glaucoma, secondary glaucoma, and paediatric glaucoma. The types of surgeries were categorised as internal filtration, external filtration, and cyclodestruction surgery based on the pathway of aqueous humor outflow. The trend of these glaucoma surgeries in the sample of patients with different types of glaucoma was then analysed. RESULTS: The number of patients hospitalised for glaucoma surgery increased yearly, from 752 in 2015 to 1373 in 2021, at the Eye Hospital of Wenzhou Medical University. Regarding the patients diagnosed with primary open angle glaucoma, internal filtration surgery increased from 27.40% of the sample to 54.40% of the sample, while external filtration surgery decreased from 71.50% to 44.20% between 2015 and 2021. For paediatric glaucoma, internal filtration surgery increased from 37.50% in 2015 to 88.20% in 2021. Whilst different types of surgeries were performed on the sample of patients with secondary glaucoma, the proportion of internal filtration surgery also showed an increase from 18.20% in 2015 to 40.90% in 2021. Meanwhile, internal filtration surgery in the patient sample with primary angle-closure glaucoma already accounted for over 70.00% in 2015, and showed a small increase by 2021. CONCLUSION: As surgical technology and surgical experience continue to elevate and improve, the range of glaucoma surgeries are correspondingly evolving. This study find that internal filtration surgeries accounted for an increasing proportion of treatments in the surgical management of glaucoma between 2015 and 2021.

Circulating S100A8/A9 Levels Reflect Intraocular Inflammation in Uveitis Patients.

Purpose: To investigate whether there is an association between circulating S100A8/A9 levels and uveitis activity.Methods: A total of 549 plasma samples were collected from uveitis patients and non-uveitic controls.Results: S100A8/A9 plasma levels were elevated in uveitis patients compared to non-uveitic controls (P < 0.001). S100A8/A9 plasma levels in patients with active acute anterior uveitis (AAU) were significantly elevated and remarkably decreased in parallel with the severity of intraocular inflammation after corticosteroid treatment (P < 0.001). S100A8/A9 plasma levels were also higher in AAU patients with ankylosing spondylitis (AS) than in patients without AS (P = 0.02). S100A8/A9 plasma levels were significantly increased in uveitis patients with elevated C-reactive protein (CRP, P = 0.004) or erythrocyte sedimentation rates (ESR, P = 0.049) levels compared to uveitis patients with normal CRP or ESR values.Conclusion: Circulating S100A8/A9 might be a useful biomarker for the measurement of intraocular inflammation.

Elevated Plasma Levels of Drebrin in Glaucoma Patients With Neurodegeneration.

Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Aberrations in several cytoskeletal proteins, such as tau have been implicated in the pathogenesis of neurodegenerative diseases, could be initiating factors in glaucoma progression and occurring prior to axon degeneration. Developmentally regulated brain protein (Drebrin or DBN1) is an evolutionarily conserved actin-binding protein playing a prominent role in neurons and is implicated in neurodegenerative diseases. However, the relationship between circulating DBN1 levels and RGC degeneration in glaucoma patients remains unclear. In our preliminary study, we detected drebrin protein in the plasma of glaucoma patients using proteomic analysis. Subsequently, we recruited a total of 232 patients including primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG) and Posner-Schlossman syndrome (PS) and measured its DBN1 plasma levels. We observed elevated DBN1 plasma levels in patients with primary glaucoma but not in patients with PS compared to nonaxonopathic controls. Interestingly, in contrast to tau plasma levels increased in all groups of patients, elevated drebrin plasma levels correlated with retinal nerve fiber layer defect (RNFLD) in glaucoma patients. To further explore the expression of DBN1 in neurodegeneration, we conducted experiment of optic nerve crush (ONC) models, and observed increased expression of DBN1 in the serum as well as in the retina and then decreased after ONC. This result reinforces the potentiality of circulating DBN1 levels are increased in glaucoma patients with neurodegeneration. Taken together, our findings suggest that circulating DBN1 levels correlated with RNFLD and may reflect the severity of RGCs injury in glaucoma patients. Combining measurement of circulating drebrin and tau levels may be a useful indicator for monitoring progression of neurodegenerative diseases.

Endoscopically controlled goniosynechialysis in managing synechial angle-closure glaucoma.

PURPOSE: To propose a new surgical technique for optimized visualization of the chamber angle using ophthalmic microendoscope in goniosynechialysis (GSL). METHODS: Patients who had acute angle-closure glaucoma with peripheral anterior synechiae or patients with flat anterior chamber after trabeculectomy underwent endoscopically controlled GSL. Ophthalmic endoscope was used before, during, and immediately after GSL to minimize the procedure of GSL and to ensure that the trabecular meshwork was exposed and the majority of the angle was opened after endoscopically controlled GSL. Intraoperative complications, postoperative visual acuity, intraocular pressures (IOPs), and complications were all evaluated. RESULTS: Twelve eyes of twelve patients underwent the operation and the mean follow-up was 7.4+/-1.4 months (range: 6 to 10 mo). The mean preoperative IOP was 42.89+/-15.81 mm Hg. The mean postoperative IOP at the most recent follow-up was 12.72+/-3.48 mm Hg. The absolute success rate (IOP <21 mm Hg without medication) was 8 of 10. Visual acuity improved in 11 of 12 patients (91.7%). No significant intraoperative complications, such as iridodialysis, occurred in any patient. Postoperative complications included hyphema and transient corneal decompensation. CONCLUSIONS: Endoscope conveniently provided the surgeon an optimized visualization of the anterior chamber angle. This enhanced visualization and convenience promises accuracy and safety when performing GSL.

Measurement of retinal nerve fiber layer in primary acute angle closure glaucoma by optical coherence tomography.

PURPOSE: To detect the objective structure changes of the retinal nerve fiber layer (RNFL) in primary acute angle closure glaucoma (PAACG) and to evaluate the efficacy of quantitative assessment of RNFL thickness with optical coherence tomography (OCT). PATIENTS AND METHODS: Forty patients who had unilateral PAACG attack in the first 4 months after remission and 40 single eyes from 40 normal controls were enrolled in this cross-sectional study. For all cases, PAACG had resolved after treatment. Using the Stratus OCT, the RNFL was assessed in both eyes within 2 weeks after PAACG, and again after 4 months. The OCT parameters were compared among normal controls, the unaffected fellow eyes, and the attacked eyes within 2 weeks and at 4 months after remission. Of the 40 patients, 14 PAACG patients underwent 5 times measurements, respectively, within 2 weeks and at 1, 2, 3, and 4 months after intraocular pressure was controlled. Differences between affected eyes and fellow eyes for the mean RNFL thickness at various periods after remission were also compared. RESULTS: RNFL of the PAACG eyes became thicker (average: 142.6+/-22.9 microm) within 2 weeks and thinner (average: 83.6+/-19.8 microm) at 4 months after acute strike compared with the fellow unaffected and normal eyes. Significant differences were demonstrated comparing the average and 4-quadrant RNFL thicknesses for the attacked eyes with those of the normal controls (P<0.001 to 0.001) and fellow eyes (P<0.001 to 0.002) using 1-way analysis both within 2 weeks and at 4 months after remission. There was significant difference in the RNFL thickness among the 5 time points after intraocular pressure controlled in the acute strike group (P<0.001). CONCLUSIONS: Using OCT, RNFL thickness was found to increase in eyes immediately after an episode of PAACG followed by a decrease in RNFL thickness over time (up to 3 mo). This detection can aid in better understanding the pathologic retinal changes involved in PAACG, and help in the assessment and management of these patients.