Magnesium Depletion Score Predicts Diabetic Retinopathy Risk among Diabetes: Findings from NHANES 2005-2018.

Magnesium is essential for material and energy metabolism. The magnesium depletion score (MDS) is recognized as a more valuable and reliable predictor of body magnesium status than any other clinical used markers such as serum and urine magnesium. However, research on the relationship between MDS and diabetic retinopathy (DR) is limited. As a result, the current study sought to assess this issue in diabetic samples from a large population-based database in the United States. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. MDS was calculated, and multivariate logistic regression analysis was applied to evaluate the presence of association between variables and DR risk. A total of 4308 participants was comprised in this study. Samples with DR consumed less magnesium (259.1 ± 113.6 vs 269.8 ± 113.2 mg, P < 0.001), and their MDS levels differed significantly from non-DR participants (P < 0.001). Increased dietary magnesium was linked to a lower incidence of DR (all P for trend < 0.05), and patients with a high level of MDS were more prone to DR (P = 0.001). Furthermore, subgroup analysis revealed that high (Q3) amount magnesium supplements was associated with lower DR risk when MDS was none to low or middle level (both P = 0.02). Our results indicated that MDS levels are associated with DR risk and that magnesium supplementation is benefit to DR prevention.

Dysregulation of circulating CD4 + CXCR5 + PD-1+ T cells in diabetic retinopathy.

AIMS: We aimed to determine an association between follicular helper T (Tfh) cells and Bcl-6 and CXCL13 levels and determine the role of Tfh cells, Bcl-6, and CXCL13 serum levels in the pathogenesis of diabetic retinopathy (DR) since Tfh cells have an important role in type 1 diabetes; however, their role in type 2 diabetes-related DR requires exploration. METHODS: Blood samples were collected from 24 patients with non-proliferative diabetic retinopathy (NPDR), 20 with proliferative diabetic retinopathy (PDR), and 18 age- and sex-matched healthy volunteers. Flow cytometry detected CD4 + CXCR5 + PD1+ Tfh cells. Serum Bcl-6 and CXCL13 levels were determined using enzyme-linked immunosorbent assay. RESULTS: CD4 + CXCR5 + PD-1+ Tfh cell percentages in peripheral blood and serum levels of Bcl-6 and CXCL13 in the non-proliferative DR (NPDR) and proliferative DR (PDR) groups' were significantly higher than those in healthy individuals. The proportion of Tfh cells in DR patients' peripheral blood positively correlated with Bcl-6 and CXCL13 serum levels, DR course severity, Fasting blood glucose, glycosylated hemoglobin and body mass index. CONCLUSIONS: The increased circulating Tfh cells, serum Bcl-6 levels, and CXCL13 levels of DR patients with type 2 diabetes suggested that circulating Tfh cells and the germinal center response may have a role in the occurrence and development of DR.

Reduced serum magnesium is associated with the occurrence of diabetic macular edema in patients with diabetic retinopathy: A retrospective study.

Serum magnesium levels have been reported to reflect the risk of diabetic retinopathy (DR); however, the effect of serum magnesium level on diabetic macular edema (DME) remains unclear. Here, we investigated the association between the serum magnesium levels and DME in patients with DR. Patients with DR were recruited between January 2018 and June 2021. A total of 519 such patients were included in this study. All patients underwent a standardized clinical ophthalmic examination by an experienced ophthalmologist, and an assay was conducted to determine the serum magnesium concentration. Compared with the non-DME group, the DME group had a higher proportion of insulin use and a higher level of serum ischemia-modified albumin and fasting plasma glucose. The serum magnesium and calcium levels were lower in the DME group than in the non-DME group (P < 0.05). Higher magnesium levels were negatively associated with DME after adjustment for relevant covariates. Compared with the participants in the lowest magnesium quartile, those in the fourth quartile showed a significantly lower risk of DME after adjustment [odds ratio (OR), 0.294; 95% confidence interval, 0.153-0.566; P < 0.0001]. Considering the potentially different effects of serum magnesium on the development of DME in patients with DR based on age, DR staging and insulin use, stratified analysis was performed by considering these factors. Among insulin-using patients with non-proliferative DR who were < 66 years of age, those in the third and fourth quartile of serum magnesium were less likely to develop DME than those in the lowest quartile of serum magnesium [OR (95% CI), 0.095 (0.014-0.620), 0.057 (0.011-0.305); P = 0.014, 0.001]. Overall, a higher serum magnesium level was associated with a lower risk of DME in patients with DR. Furthermore, patients with DR who used insulin were more likely to develop DME. Long-term studies on oral magnesium supplements are needed to determine whether maintaining the serum magnesium levels in a higher physiological range can reduce the risk of DME in patients with DR.

Pars Plana Ahmed Valve Implantation for Vitrectomized Eyes With Refractory Glaucoma.

This study aimed to analyze the surgical outcomes of pars plana Ahmed valve implantation in vitrectomized eyes with refractory glaucoma. We performed a retrospective case review of consecutive patients with refractory glaucoma after undergoing pars plana vitrectomy who underwent pars plana Ahmed valve implantation between July 2019 and December 2020 at the glaucoma unit of the Affiliated Changshu Hospital of Xuzhou Medical University (Changshu, China). All the patients were followed up for ≥12 months postoperatively. We recorded pre- to postoperative changes in best-corrected visual acuity (BCVA), intraocular pressure (IOP), number of anti-glaucoma medication, corneal endothelial count, and surgical complications, if any. There was a significant improvement in the median BCVA from 2.30 (0.87, 2.30) logMAR preoperatively to 1.70 (0.70, 2.30) logMAR at discharge and 1.0 (0.52, 1.85) at final examination (p = 0.011, p = 0.001). Compared with the preoperative IOP level, there was a significant decrease in the postoperative IOP at each postoperative time point (p < 0.001). There was a significant reduction in the median number of anti-glaucoma drugs (including postoperative ocular massage), from 3.00 (2.00, 3.00) preoperatively to 0.00 (0.00, 1.00) at the last follow-up postoperative examination (p < 0.001). A 29-year-old woman with proliferative diabetic retinopathy who underwent surgical treatment at 5 months postoperatively for fibrous wrapping formed around the plate of the Ahmed valve showed an IOP of 14 mmHg at the last follow-up. Our findings indicated that pars plana Ahmed valve implantation can be safely performed for managing vitrectomized eyes with refractory glaucoma.

Intravitreous injection of conbercept for bullous retinal detachment: A case report.

BACKGROUND: Diffuse retinal pigment epitheliopathy (DRPE) associated with bullous retinal detachment is a severe variant of DRPE that is frequently misdiagnosed and often improperly treated. CASE SUMMARY: A 36-year-old female patient complained of "painless vision decline in the left eye with obscuration for 10 d". Slit-lamp microscopic fundus examination revealed white-yellow subretinal exudates in the posterior pole in both eyes, retinal detachment with shifting subretinal fluid in the left eye, and no retinal hiatus. Fundus fluorescein angiography revealed multiple subretinal leakage foci and localized hypofluorescent lesions with patched hyperfluorescence. There was fluorescence leakage in the retinal vessels in the retinal detachment area and occluded blood vessels in the lower and peripheral areas. Indocyanine green angiography revealed multifocal lamellar hyperfluorescence in the middle stage and low fluorescence in the retinal detachment area in the late stage. Retinal anatomical reduction significantly improved with intravitreal conbercept injections. CONCLUSION: Intravitreal injection of conbercept can anatomically reattach the retina in patients with bullous retinal detachment.

Vitreous Decompression Combined with Phacoemulsification for Medically Unresponsive Acute Angle Closure.

The management of acute angle closure combined with an extremely shallow anterior chamber and cataract remains complex. This study evaluated a technique of vitreous needle aspiration combined with phacoemulsification for the treatment of acute angle closure with continuous high intraocular pressure (IOP). We retrospectively reviewed the results of vitreous needle aspiration combined with phacoemulsification in 17 eyes (17 patients) with acute angle closure with continuous high IOP and coexisting visually significant cataracts between September 2018 and April 2020 at the glaucoma unit of the affiliated Changshu Hospital of Xuzhou Medical University. The main outcomes were the best corrected visual acuity (BCVA), IOP, anterior chamber depth (ACD), angle open distance 500 (AOD500), number of antiglaucoma medications, and surgery-associated complications. There were no complications during phacoemulsification and a foldable acrylic intraocular lens was implanted in the capsular bag in all 17 patients. For all patients, vitreous needle aspiration was successful at the first attempt. The BCVA improved from 2.02 ± 0.54 logMAR preoperatively to 0.73 ± 0.57 logMAR postoperatively at the final examination (p < 0.001). The mean IOP was 54.47 ± 5.33 mmHg preoperatively and 15.59 ± 2.35 mmHg at the final examination (p < 0.001) without any medication. The ACD was 1.70 ± 0.16 mm preoperatively and 3.35 ± 1.51 mm at the final examination (p < 0.001). The AOD500 was 0.07 ± 0.02 mm preoperatively and 0.51 ± 0.04 mm at the final examination (p < 0.001). Our vitreous needle aspiration technique can be performed safely in phacoemulsification for the management of acute angle closure with continuous high IOP.

Cyclophotocoagulation under Microscopy Combined with Phacoemulsification for Primary Angle-Closure Glaucoma.

The purpose of this study was to evaluate the safety and efficacy of cyclophotocoagulation under microscopy combined with phacoemulsification in patients with primary chronic angle-closure glaucoma. We retrospectively reviewed the results of cyclophotocoagulation under microscopic direct vision combined with phacoemulsification in 35 eyes (35 patients) with primary chronic angle-closure glaucoma and coexisting visually significant cataracts, treated between January 2017 and April 2020 at the glaucoma unit of the affiliated Changshu Hospital of Xuzhou Medical University. All patients were followed up for at least 12 months postoperatively. The preoperative to postoperative changes in best-corrected visual acuity (BCVA), intraocular pressure (IOP), number of antiglaucoma medications, and surgery-associated complications were recorded. The BCVA improved from 1.15 ± 0.91 logMAR preoperatively to 0.86 ± 0.82 logMAR at the final postoperative examination (Z = -3.62, P < 0.0001). The mean IOP was 36.63 ± 13.50 mmHg preoperatively and 15.14 ± 3.19 mmHg at the final examination (Z = -5.16, P < 0.0001). The number of antiglaucoma drugs was significantly reduced from 2.23 ± 0.55 preoperatively to 0.54 ± 0.86 at the final postoperative examination (Z = -5.26, P < 0.0001). The absolute value of the mean defect and retinal nerve fiber layer thickness at the last follow-up postoperatively were significantly reduced compared to preoperative values (Z = -3.35, P=0.001; Z = -4.56, P < 0.001, respectively). One patient experienced an explosive suprachoroidal hemorrhage during the operation. The sclera was incised at the corresponding site of the intraoperative hemorrhage. The operation was continued once there was no active bleeding, and the outcome was satisfactory. None of the patients required additional surgery to treat complications. Thus, cyclophotocoagulation under microscopic direct vision combined with phacoemulsification can be performed safely for the management of primary angle-closure glaucoma.

PTEN knockdown with the Y444F mutant AAV2 vector promotes axonal regeneration in the adult optic nerve.

The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog (PTEN) enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated (Y444F) AAV2 vector to efficiently express a short hairpin RNA (shRNA) for silencing PTEN expression in retinal ganglion cells. We evaluated cell survival and axonal regeneration in a rat model of optic nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or Y444F mutant AAV2 (both carrying shRNA to PTEN) 4 weeks before optic nerve axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector enhanced retinal ganglia cell survival and stimulated axonal regeneration to a greater extent 6 weeks after axotomy. Moreover, post-axotomy injection of the Y444F AAV2 vector expressing the shRNA to PTEN rescued ~19% of retinal ganglion cells and induced axons to regenerate near to the optic chiasm. Taken together, our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes retinal ganglion cell survival and stimulates long-distance axonal regeneration after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising gene therapy tool for treating optic nerve injury.

Tyrosine-mutated AAV2-mediated shRNA silencing of PTEN promotes axon regeneration of adult optic nerve.

Activating PI3K/AKT/mTOR signaling pathway via deleting phosphatase and tensin homolog (PTEN) has been confirmed to enhance intrinsic growth capacity of neurons to facilitate the axons regeneration of central nervous system after injury. Considering conditional gene deletion is currently not available in clinical practice, we exploited capsid residue tyrosine 444 to phenylalanine mutated single-stranded adeno-associated virus serotype 2 (AAV2) as a vector delivering short hairpin RNA to silence PTEN to promote retinal ganglion cells (RGCs) survival and axons regeneration in adult rat optic nerve axotomy paradigm. We found that mutant AAV2 displayed higher infection efficiency to RGCs and Müller cells by intravitreal injection, mediated PTEN suppression, resulted in much more RGCs survival and more robust axons regeneration compared with wild type AAV2, due to the different extent of the mTOR complex-1 activation and glutamate aspartate transporter (GLAST) regulation. These results suggest that high efficiency AAV2-mediated PTEN knockdown represents a practicable therapeutic strategy for optic neuropathy.

Knockout of Ccr2 alleviates photoreceptor cell death in rodent retina exposed to chronic blue light.

Age-related macular degeneration (AMD), the leading cause of visual loss after the age of 60 years, is a degenerative retinal disease involving a variety of environmental and hereditary factors. Although it has been implicated that immune system is involved in the disease progression, the exact role that microglia has is still unclear. Here we demonstrated that knockout of Ccr2 gene could alleviate photoreceptor cell death in mice retinas exposed to chronic blue light. In Ccr2-/- mice, a damaged microglia recruitment was shown in retina and this could protect the visual function in electroretinogram and alleviate the photoreceptor apoptosis, which thus helped attenuate the blue light-induced retinopathy. We further found an increased co-location of NLRP3, Iba-1, and IL-1ß in fluorescence and a concomitant increased protein expression of NLRP3, caspase-1, and IL-1ß in western blotting in chronic blue light-induced retinopathy. Moreover, the activation of microglia and their cellular NLRP3 inflammasomes occurred as an earlier step before the structural and functional damage of the mice retinas, which collectively supported that microglial NLRP3 inflammasome might be the key to the chronic blue light-induced retinopathy.