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.

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.

Long-term outcomes of ciliary sulcus versus capsular bag fixation of intraocular lenses in children: An ultrasound biomicroscopy study.

PURPOSE: To evaluate the long-term outcomes of ciliary sulcus versus capsular bag fixation of intraocular lenses (IOLs) in children after pediatric cataract surgery. METHODS: IOL was implanted in the ciliary sulcus in 21 eyes of 14 children, and in the capsular bag in 19 eyes of 12 children for the treatment of pediatric cataract in an institutional setting. Ultrasound biomicroscopy (UBM) was performed. Main outcome measures included IOL decentration, IOL tilt, anterior chamber depth (ACD), angle-opening distance at 500 µm (AOD500), trabecular-iris angle (TIA), best-corrected visual acuity (BCVA), intraocular pressure (IOP), and incidence of postoperative complications. RESULTS: The mean follow-up period was 6.81 ± 1.82 years. Comparing to the capsular bag fixation group, the ciliary sulcus fixation group had higher vertical IOL decentration, horizontal IOL tilt, and vertical IOL tilt (p = 0.02, 0.01,0.01, respectively), higher incidence of iris-IOL contact and peripheral anterior synechia (p = 0.001, 0.03, respectively), smaller ACD, AOD500, and TIA (p = 0.02, 0.03, 0.04, respectively), higher mean IOP (17.10 ±6.06 mmHg vs.14.15± 4.74 mmHg, p = 0.01), and higher incidence of secondary glaucoma (28.57% vs. 10.53%, p = 0.007).There was no significant difference between the two groups with regard to the BCVA, refractive errors, incidence of myopic shift, nystagmus, strabismus, and visual axis opacity. CONCLUSIONS: Ciliary sulcus fixation of IOLs in pediatric eyes may increase IOL malposition and crowding of the anterior segment, and may associate with a higher risk of secondary glaucoma compared to capsular bag fixation of IOLs.

The long-term anterior segment configuration after pediatric cataract surgery and the association with secondary glaucoma.

Secondary glaucoma constitutes major sight-threatening complication of pediatric cataract surgery, yet the etiology remains unclear. The purpose of this study was to investigate the long-term anterior segment configuration and the association with secondary glaucoma in pediatric pseudophakia. Ultrasound biomicroscopy (UBM) was performed on 40 eyes of 26 children underwent pediatric cataract surgery and intraocular lens (IOL) implantation. The anterior chamber depth (ACD), angle-opening distance at 500 µm (AOD500), trabecular-iris angle (TIA), central corneal thickness (CCT), structural abnormities, IOL position, IOP, and incidence of glaucoma were evaluated. High insertion of iris, in which the iris root is attached more anteriorly than normal, was seen in 13 eyes (32.50%). IOL was located in the capsular bag in 19 eyes and in the ciliary sulcus in 21 eyes. Logistic regression analysis identified high insertion of iris (OR 3.40, 95% CI 1.03-11.17, p = 0.03) and IOL implantation in sulcus (OR 1.39, 95% CI 1.07-4.85, p = 0.04) as independent risk factors for glaucoma. The presence of high insertion of iris and IOL implantation in ciliary sulcus may increase the long-term risk of the development of secondary glaucoma after pediatric cataract surgery.

[Comparison of effects of secondary in-the-bag and sulcus intraocular lens implantation in pediatric aphakia after congenital cataract operation].

OBJECTIVE: To compare the results of secondary in-the-bag intraocular lens (IOL) implantation with secondary sulcus IOL implantation in the eyes which received cataract extraction during early infancy. METHODS: A case control study. We selected 60 eyes of 44 patients with pediatric aphakia that meet the inclusion criterion in Affiliated Eye Hospital of Wenzhou Medical College from September 2005 to August, 2011. Thirty eyes received in-the-bag secondary IOL implantation and were compared with 30 eyes that received secondary sulcus IOL implantation. Data were collected for the ages at cataract extraction and at secondary IOL implantation, the preoperative axial length, the length of follow-up, postoperative complications, postoperative best-corrected visual acuity (BCVA) and refraction. When sufficient capsular opening was possible or capsular support deemed adequate, an IOL was placed within the capsular bag, otherwise the IOL was implanted in the sulcus. The χ(2) test or Fisher exact test was used to compare complications between the in-the-bag and sulcus groups. The independent-samples t test or Wilcoxon rank sum test was used to compare demographic, preoperative and postoperative refractive relevant data between the in-the-bag and sulcus groups. RESULTS: The median of 1-week-postoperative spherical equivalent clustered 1.00 D (range, -2.13 to 3.38 D) for in-the-bag group and 0.69 D (range, -2.25 to 2.38 D) for the sulcus group (Z = -1.01, P = 0.31). The median of 1-year-postoperative spherical equivalent clustered 0.00 D (range, -3.50 to 3.00 D) for in-the-bag and -0.50 D (range, -3.25 to 2.50 D) for the sulcus (Z = -0.53, P = 0.60). The last follow-up BCVA was available in 23 of 30 eyes in the in-the-bag group and 22 of 30 eyes in the sulcus group. The median of visual outcome clustered around 0.20 D (range, 0.05 to 0.70 D) for in-the-bag and 0.20 D (range, 0.05 to 0.60 D) for the sulcus (Z = -1.06, P = 0.29). The rate of nystagmus was significantly greater in the sulcus group (63.3%) than in the in-the-bag group (33.3%) (χ(2) = 5.41, P = 0.02). The incidence of strabismus, glaucoma and corneal calcific band keratopathy in the in-the-bag group were 36.7% (11/30), 3.0% (1/30) and 10.0% (3/30); 23.3% (7/30), 3.0% (1/30) and 13.3% (4/30) in the sulcus group, respectively. There were no significant differences between the two groups (Strabismus: χ(2) = 1.27, P = 0.26; Glaucoma: χ(2) = 0.16, P = 0.69; corneal calcific band keratopathy: P = 1.00). CONCLUSIONS: For children who have been aphakic due to receiving cataract extraction during their early infancy, there was no significant difference in both postoperative complications and visual acuity between the secondary in-the-bag IOL implantation and secondary sulcus IOL implantation during 1 year to 6 years follow-up time after the implantation surgery.

Visual and optical performance of eyes with different corneal spherical aberration implanted with aspheric intraocular lens.

AIM: To compare the visual and optical performance of eyes with different corneal spherical aberration (SA) implanted with spherical aberration-free intraocular lens (IOLs). METHODS: Thirty-six patients with different corneal SA had phacoemulsification with implantation of spherical aberration-free IOLs. Patients were divided into 3 groups according to the value of preoperative corneal SA. Eyes with corneal SA <0.10µm were assigned to group A, those with 0.10 ≤corneal SA <0.20µm to Group B, and those with 0.20≤ corneal SA <0.35µm to Group C. Best-corrected visual acuity (BCVA), contrast sensitivity, corneal SA, total ocular aberrations, and depth of focus were recorded 3 months postoperatively. Distance-corrected near and intermediate visual acuity was studied to measure depth of focus. RESULTS: BCVA and contrast sensitivity were similar between groups. There were no significant differences in distance-corrected near or intermediate visual acuity. Corneal SA was similar before and 3 months after surgery in the 3 groups. With a 5.0mm pupil diameter, root mean square values for total ocular higher-order aberrations (HOAs) were lower in groups A and B than in group C. Total ocular SA was lower in group A than in groups B and C. SA was also lower in group B than in group C. Coma and trefoil were similar between the groups. CONCLUSION: Implantation of spherical aberration-free IOLs in eyes with different corneal SA results in similar visual performance at BCVA, contrast sensitivity and depth of focus.