GMFB/AKT/TGF-ß3 in Müller cells mediated early retinal degeneration in a streptozotocin-induced rat diabetes model.

Retinal degeneration, characterized by Müller cell gliosis and photoreceptor apoptosis, is considered an early event in diabetic retinopathy (DR). Our previous study proposed that GMFB may mediate diabetic retinal degeneration. This study identified GMFB as a sensitive and functional gliosis marker for DR. Compared to the wild type (WT) group, Gmfb knockout (KO) significantly improved visual function, attenuated gliosis, reduced the apoptosis of neurons, and decreased the mRNA levels of tumor necrosis factor α (Tnf-α) and interleukin-1ß (Il-1ß) in diabetic retinas. Tgf-ß3 was enriched by hub genes using RNA sequencing in primary WT and KO Müller cells. Gmfb KO significantly upregulated the transforming growth factor (TGF)-ß3 protein level via the AKT pathway. The protective effect of TGF-ß3 in the vitreous resulted in significantly improved visual function and decreased the number of apoptotic cells in the diabetic retina. The protection of Gmfb KO in primary Müller cells against high glucose (HG)-induced photoreceptor apoptosis was partially counteracted by TGF-ß3 antibody and administration of TGFBR1/2 inhibitors. Nuclear receptor subfamily 3 group C member 1 (NR3C1) binds to the promoter region of Gmfb and regulates Gmfb mRNA at the transcriptional level. NR3C1 was increased in the retinas of early diabetic rats but decreased in the retinas of late diabetic rats. N'-[(1E)-(3-Methoxyphenyl)Methylene]-3-Methyl-1H-Pyrazole-5-Carbohydrazide (DS-5) was identified as an inhibitor of GMFB, having a protective role in DR. We demonstrated that GMFB/AKT/TGF-ß3 mediated early diabetic retinal degeneration in diabetic rats. This study provides a novel therapeutic strategy for treating retinal degeneration in patients with DR.

Posterior capsular radial sign: a novel method to confirm anterior vitreous cortex resection in phacovitrectomy.

BACKGROUND: The main purpose of this paper is to introduce a method that can accurately locate the posterior capsule of the lens to facilitate a relatively complete resection of the anterior vitreous body. METHODS: A total of 51 patients in the experimental group and control group were enrolled in this study. Phacoemulsification combined with vitrectomy was performed in all cases. After the cataract procedure was completed in the control group, the surgeon performed a conventional anterior vitrectomy with the operative eye. In the experimental group, anterior vitrectomy was performed according to the threadiness corrugation of the posterior capsule of the lens. During the operation, with the help of triamcinolone, two surgeons confirmed the resection of the anterior vitreous cortex; the best corrected visual acuity and intraocular pressure of all patients were recorded at 1 week, 1 month and 3 months after surgery. RESULTS: Fifty patients underwent phacoemulsification combined with vitrectomy, except one patient in the experimental group who was lost to follow-up. After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. There was no significant difference in preoperative visual acuity between the two groups (t = 0.83, P = 0.25). Both groups had varying degrees of improvement in best corrected visual acuity at 1 week, 1 month and 3 months after surgery. Moreover, there was no significant difference in BCVA between the two groups at the three follow-up time points (t=-1.15, -1.65, -1.09, P = 0.53, 0.21, 0.23). After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. Incomplete resection of the anterior vitreous cortex was observed in 2 patients in each group, but there was no significant difference (χ2 = 7.81, P > 0.05). CONCLUSION: In the process of cataract surgery combined with vitrectomy, thready corrugation appears in the posterior capsule of the lens and is an important sign of its localization. Anterior vitrectomy can be accomplished safely and effectively with the help of thread-like corrugation, and the surgical effect is almost the same as that of traditional surgery. Especially suitable for beginners in vitreous surgery.

Corneal densitometry: an innovative method to quantitatively evaluate corneal changes after phacovitrectomy.

BACKGROUND: To quantitatively investigate corneal changes and the correlation between corneal densitometry (CD) and endothelial parameters after phacovitrectomy. METHODS: Thirty-eight eyes with idiopathic full-thickness macular holes (iFTMHs) and cataracts underwent phacovitrectomy. Examinations were conducted at baseline and Day 1, Day 7, Month 1, and Month 3 postoperatively. CD and central corneal thickness (CCT) were measured using Pentacam. Corneal endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX) were measured using specular microscopy. RESULTS: ECD and HEX significantly decreased after surgery and the change in HEX occurred prior to CV. CCT increased immediately after surgery and recovered 3 months postoperatively. CD values increased significantly 1 day after surgery and then gradually decreased. For CD in the 0-2 mm zone, it took 1 month to recover in the central and posterior layers and 3 months in the anterior and total layers. For CD in the 2-6 mm zone, the central layer recovered at Day 7, the anterior and total layers recovered at 1 month, and the posterior layer did not recover until 3 months postoperatively. The CD within all layers in the 0-2 mm zone was positively correlated with CCT. Posterior CD in the 0-2 mm zone was negatively correlated with ECD and HEX. CONCLUSIONS: CD is not only correlated with CCT, ECD, and HEX but also reflects the state of the whole cornea and each layer. CD can be an objective, rapid, and noninvasive tool that reflects corneal health and undetectable edema and monitors the process of lesion repair. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (31/10/2021, ChiCTR2100052554).

An optional surgical technique for obtaining lamellar donor grafts: a pilot study.

BACKGROUND: To evaluate the surface quality and thickness uniformity of lamellar donor grafts using an optional surgical technique called reversed manual dissection (RMD) in porcine corneas. METHODS: Twenty-four paired porcine corneas (48 eyes) were numbered 1 to 24 and divided into 6 groups. All left corneas were assigned to conventional manual dissection (CMD), and all right corneas were assigned to RMD. Each group contained 8 corneas. For Groups I, II, and III, 30, 50, and 70% of the entire corneal thickness was dissected using CMD. For groups IV, V, and VI, 70, 50, and 30% of the entire corneal thickness was dissected using RMD. The residual stromal thickness was examined by anterior segment optical coherence tomography (ASOCT) to assess the thickness uniformity and scanning electron microscopy (SEM) to assess the surface quality. RESULTS: The thickness uniformity of the lamellar grafts between each paired group was not significantly different (p > 0.05). The qualitative surface roughness grading (QiSR) evaluated by masked observers through SEM was significantly higher in the RMD groups (p < 0.001). The quantitative surface roughness grading (QnSR) acquired from the Mountains software was significantly lower in the RMD groups (p < 0.001). CONCLUSIONS: RMD is an optional surgical technique for obtaining porcine lamellar grafts. The thickness uniformity of RMD is comparable to that of CMD, and a smoother surface with fewer ridges and roughness is achieved compared to CMD.

Long-Term Stability of Intraocular Lens with Trimmed or Untrimmed Haptics in Yamane Sutureless Intrascleral Fixation Technique.

BACKGROUND In intraocular lens (IOL) sutureless intrascleral fixation using the Yamane technique, untrimmed haptics may be overlong in some cases due to varied haptic lengths and individual differences. However, whether trimming the haptic affects IOL stability remains unknown. MATERIAL AND METHODS Thirty-nine eyes of 39 patients who underwent Yamane sutureless intrascleral fixation surgery between October 2017 and February 2018 were analyzed retrospectively. Nineteen patients underwent surgery with untrimmed haptics and 20 patients with trimmed haptics. The slit-lamp examination, best-corrected visual acuity (BCVA), corneal endothelial cell density (ECD), IOL position, and complications were assessed. RESULTS The mean follow-up periods in the untrimmed and trimmed groups were 27.84±2.89 months and 27.85±2.41 months, respectively. The BCVA improved and ECD decreased in both groups postoperatively (all P<0.01). No significant differences were seen between the 2 groups in postoperative BCVA, postoperative ECD, IOL tilt at 3 months and 24 months, and IOL decentration at 3 months (all P>0.05). There were significant differences between the 2 groups in IOL decentration at 24 months (P<0.05). Compared with postoperative 3 months, both the postoperative IOL tilt and decentration at 24 months increased in the 2 groups (all P<0.01). Postoperative complications included IOL elevation (11% in the untrimmed group and 10% in the trimmed group), as well as haptic extrusion (16% in the untrimmed group). CONCLUSIONS The position of the IOL may change with time, but trimming the haptic to an optimum length tends to provide greater IOL stability.

Staphylococcus-associated marginal keratitis secondary to pterygium surgery: a case report.

BACKGROUND: Staphylococcus-associated marginal keratitis is an immune-mediated corneal disorder mainly secondary to chronic blepharoconjunctivitis. We report a rare case of Staphylococcus-associated marginal keratitis following pterygium excision. To the best of our knowledge, none of the previous literature has described such an acute complication after pterygium surgery. CASE PRESENTATION: We report a case of a 50-year-old woman who suffered from pterygium in the left eye and underwent pterygium surgery. After surgery, slit-lamp examination showed an incomplete ring-shaped creamy white infiltrate. Corneal pathogenic microbial detection was negative. Staphylococcus aureus was found on the upper eyelid margin of the affected eye. Therefore, she was clinically diagnosed with Staphylococcus-associated marginal keratitis. The infiltrate was gradually absorbed after steroids, topical antibiotics, and lubricant eye drops were administered. After 2 years of follow-up, neither corneal infiltrate nor pterygium recurrence was observed. CONCLUSION: Staphylococcus-associated marginal keratitis is an immune reaction mainly secondary to chronic blepharoconjunctivitis, which usually activates an antigen-antibody reaction with complementary activation and neutrophil infiltration in patients sensitized to staphylococcal antigens. Early detection and treatment is of great importance. Topical steroids are effective and should be initiated early once pathogenic microbial infections are excluded. Although chronic staphylococcal blepharoconjunctivitis is a common disease, ophthalmologists should pay more attention to it to avoid potential complications.

Individualized penetrating keratoplasty using edge-trimmed glycerol-preserved donor corneas for perforated corneal ulcers.

PURPOSE: To report a surgical technique and the surgical outcomes of individualized penetrating keratoplasty (PK) using edge-trimmed glycerol-preserved donor corneas for perforated corneal ulcers. METHODS: Fourteen perforated eyes from 14 patients who underwent individualized PK using edge-trimmed glycerol-preserved donor corneas, were included in the retrospective study. The perforations were mainly 1-2 mm in size except for one that was 2.5 × 4 mm. Three patients were treated with PK; one patient was treated with PK and a conjunctival flap; ten patients who had large ulcer areas were treated with PK combined with lamellar keratoplasty (LK). Donor corneas were preserved in sterile pure glycerol at - 80 °C. Corneal grafts were specially edge-trimmed to match the perforation, and then sutured onto the recipient bed avoiding the visual axis. RESULTS: All 14 patients recovered anatomical integrity without reinfections of the treated eyes. All patients had improved graft transparency and uncorrected visual acuity after surgery. Among them, four patients suffered from short-term postoperative complications and recovered quickly; four patients suffered from long-term postoperative complications, of them, one was performed further treatment. CONCLUSION: After individualized PK using glycerol-preserved donor corneas, all perforated corneal ulcers were stably controlled by the end of the follow-up period. This modified surgical technique can be a potential treatment choice for patients with perforated corneal ulcers.

Petaloid technique and prognostic significance of macular hole shapes by optical coherence tomography for full thickness macular hole.

Surgical advancements for full-thickness macular hole (FTMH) treatment include vitrectomy, membrane peeling, and the inverted flap technique (IFT). IFT, which involves inverting the internal limiting membrane (ILM) flap over the macular hole (MH) or into the MH, improves success rates and visual recovery. However, issues like mis-aspiration during flap handling have been problematic. We introduce the petaloid technique, to position the ILM flap under air during FTMH surgery to evaluate its outcomes. This retrospective study included 28 eyes, with a mean minimum linear diameter (MLD) 472.04 ± 199.7 µm and basal diameter (BD) of 834.95 ± 593.54 µm. Primary closure of MH was achieved in 96.42% of patients, with 3.57% showing persistent MH during the 6-month follow-up. The VA improved significantly from preoperative levels at each postoperative stage, with notable increases at 3 months (0.86 ± 0.49 logMAR; p = 0.0132) and 6 months (0.77 ± 0.41 logMAR; p = 0.000081). The new closure patterns showed Type A in 28.6%, B in 14.3%, C in 28.6%, and D in 25%. Among different types of closure patterns, although VA improved in all types, significant improvement in VA was noted for type A and type C, with notable improvements at the 6-month follow-up for Type A (0.60 ± 0.23 logMAR; p = 0.02) and at the 1-month follow-up for Type C (0.62 ± 0.28 logMAR; p = 0.02). For macular hole retinal detachment in 5 eyes, the average preoperative VA was 1.86 ± 0.19 logMAR, while the final mean postoperative VA showed a significant improvement to 1.1 ± 0.40 logMAR (p = 0.021, paired t-tests). Retinal reattachment was achieved in all cases (5/5) without recurrent detachment post-silicone oil removal. For the prognostic significance of MH shapes identified by OCT, it can be concluded that the shape of macular holes significantly influences visual acuity outcomes at 6 months post-surgery (p = 0.037). The shape of macular holes, particularly Flask-shaped, significantly impacts visual acuity compared to other shape. The modified petaloid technique for treating FTMH proved safe and effective, with no significant complications noted.

Red Blood Cell-Hitchhiking Delivery of Simvastatin to Relieve Acute Respiratory Distress Syndrome.

Purpose: The purpose of this study is to address the high mortality and poor prognosis associated with Acute Respiratory Distress Syndrome (ARDS), conditions characterized by acute and progressive respiratory failure. The primary goal was to prolong drug circulation time, increase drug accumulation in the lungs, and minimize drug-related side effects. Methods: Simvastatin (SIM) was used as the model drug in this study. Employing a red blood cell surface-loaded nanoparticle drug delivery technique, pH-responsive cationic nanoparticles loaded with SIM were non-covalently adsorbed onto the surface of red blood cells (RBC), creating a novel drug delivery system (RBC@SIM-PEI-PPNPs). Results: The RBC@SIM-PEI-PPNPs delivery system effectively extended the drug's circulation time, providing an extended therapeutic window. Additionally, this method substantially improved the targeted accumulation of SIM in lung tissues, thereby enhancing the drug's efficacy in treating ARDS and impeding its progression to ARDS. Crucially, the system showed a reduced risk of adverse drug reactions. Conclusion: RBC@SIM-PEI-PPNPs demonstrates promise in ARDS and ARDS treatment. This innovative approach successfully overcomes the limitations associated with SIM's poor solubility and low bioavailability, resulting in improved therapeutic outcomes and fewer drug-related side effects. This research holds significant clinical implications and highlights its potential for broader application in drug delivery and lung disease treatment.

The identification of a novel shared therapeutic target and drug across all insulin-sensitive tissues under insulin resistance.

Background: To identify key and shared insulin resistance (IR) molecular signatures across all insulin-sensitive tissues (ISTs), and their potential targeted drugs. Methods: Three datasets from Gene Expression Omnibus (GEO) were acquired, in which the ISTs (fat, muscle, and liver) were from the same individual with obese mice. Integrated bioinformatics analysis was performed to obtain the differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was carried out to determine the "most significant trait-related genes" (MSTRGs). Enrichment analysis and PPI network were performed to find common features and novel hub genes in ISTs. The shared genes of DEGs and genes between DEGs and MSTRGs across four ISTs were identified as key IR therapeutic target. The Attie Lab diabetes database and obese rats were used to verify candidate genes. A medical drug-gene interaction network was conducted by using the Comparative Toxicogenomics Database (CTD) to find potential targeted drugs. The candidate drug was validated in Hepa1-6 cells. Results: Lipid metabolic process, mitochondrion, and oxidoreductase activity as common features were enriched from ISTs under an obese context. Thirteen shared genes (Ubd, Lbp, Hp, Arntl, Cfd, Npas2, Thrsp., Tpx2, Pkp1, Sftpd, Mthfd2, Tnfaip2, and Vnn3) of DEGs across ISTs were obtained and confirmed. Among them, Ubd was the only shared gene between DEGs and MSTRGs across four ISTs. The expression of Ubd was significantly upregulated across four ISTs in obese rats, especially in the liver. The IR Hepa1-6 cell models treated with dexamethasone (Dex), palmitic acid (PA), and 2-deoxy-D-ribose (dRib) had elevated expression of Ubd. Knockdown of Ubd increased the level of p-Akt. A lowing Ubd expression drug, promethazine (PMZ) from CTD analysis rescued the decreased p-Akt level in IR Hepa1-6 cells. Conclusion: This study revealed Ubd, a novel and shared IR molecular signature across four ISTs, as an effective biomarker and provided new insight into the mechanisms of IR. PMZ was a candidate drug for IR which increased p-Akt level and thus improved IR by targeting Ubd and downregulation of Ubd expression. Both Ubd and PMZ merit further clinical translational investigation to improve IR.

Safety and Efficacy of Multiple Escalating Doses of RC28-E for Neovascular Age-Related Macular Degeneration: A Phase 1b Trial.

INTRODUCTION: To assess the safety and efficacy of repeated intravitreal injections of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with neovascular age-related macular degeneration (AMD). This was a prospective, multicenter, open-label clinical trial; 37 patients with choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) letter scores between 73 and 34 were enrolled. METHODS: Treatment regimens consisted of a 3-month loading phase and a pro re nata (PRN) maintenance phase. This study included three treatment groups: the 0.5, 1.0, and 2.0 mg RC28-E groups, with escalating doses ranging from 0.5 to 2.0 mg. Patients were evaluated monthly for 48 weeks. Safety was assessed based on ocular and systemic adverse events (AEs), pharmacokinetic characteristics, and the presence of anti-RC28-E antibodies. Efficacy was assessed using the mean change in BCVA and central subfield thickness (CST) from baseline to week 48. RESULTS: Most AEs were mild or moderate. The most common AE was a minor injection-related subconjunctival hemorrhage (16.2%). The AEs did not increase with dose or repeated injections. At week 48, mean improvements in BCVA from baseline in the 0.5, 1.0, and 2.0 mg groups were 6.1 ± 8.3, 9.9 ± 10.7, and 7.6 ± 9.38 letters, respectively; mean reductions in CST in the three groups were 112.1 ± 160.5, 175.1 ± 212.4, and 128.7 ± 145.8 µm, respectively. The serum RC28-E concentrations in 95% of the patients were below the quantification limit of the assay. No significant change from baseline was observed in the mean plasma concentrations of VEGF or FGF over the 48 weeks of treatment. Pre-treatment antibodies to RC28-E were detected in 1 of the 37 patients. Antibodies to RC28-E were detected in two patients after dosing with RC28-E for 48 weeks. CONCLUSION: RC28-E was well tolerated and exhibited an overall favorable safety profile with evidence of improvements in BCVA and anatomical parameters.

Multi-functional, conformal systems with ultrathin crystalline-silicon-based bioelectronics for characterization of intraocular pressure and ocular surface temperature.

Technologies that established in vivo evaluations of soft-tissue biomechanics and temperature are essential to biological research and clinical diagnostics, particularly for a wide range of eye-related diseases such as glaucoma. Of importance are advanced bioelectronic devices for high-precise monitoring of intraocular pressure (IOP) and various ocular temperatures, as clinically proven uses for glaucoma diagnosis. Existing characterization methods are temporary, single point, and lack microscale resolution, failing to measure continuous IOP fluctuation across the long-term period. Here, this work presents a multi-functional smart contact lens, capable of rapidly capturing IOP fluctuation and ocular surface temperature (OST) for assistance for clinical use. The microscale device design is programmable and determined by finite element analysis simulation, with detailed experiments of ex vivo porcine eyeballs. Such compact bioelectronics can provide high-precise measurement with sensitivity of 0.03% mmHg-1 and 1.2 Ω °C-1 in the range of Δ2∼50 mmHg and 30-50 °C, respectively. In vivo tests of bio-integration with a living rabbit can evaluate real-time IOP fluctuation and OST, as of biocompatibility assessments verified through cellular and animal experiments. The resultant bioelectronic devices for continuous precise characterization of living eyeballs can offer broad utility for hospital diagnosis of a wide range of eye-related disorders.

Efficacy and safety of efdamrofusp alfa versus aflibercept in participants with neovascular age-related macular degeneration: a randomized, double-masked, active-controlled, non-inferiority, phase 2 trial.

PURPOSE: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: Randomized, double-masked, multicenter, active-controlled, non-inferiority phase 2 study PARTICIPANTS: A total of 231 treatment-naïve and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled. METHODS: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa or 2 mg aflibercept groups. Participants in all groups received three initial monthly loading doses, followed by treatment every 8 weeks with assessment every 4 weeks up to week 52. MAIN OUTCOME MEASURES: The primary endpoint was the mean BCVA change from baseline to week 36. The pre-specified noninferiority margin was set as -5 letters (80% CI). RESULTS: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, +12.0 letters, respectively; Least Squares (LS) mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups. CONCLUSIONS: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile.

Subepithelial white deposition in the cornea associated with silicone oil and surgical management: a case report.

A 36-year-old patient presented with a complaint of an extensive "white scar" in his right eye without pain after silicone oil presence in the vitreous cavity for 12 years. Slit-lamp microscopy revealed extensive corneal leukoplakia and mild limbus neovascularization. Anterior segment optical coherence tomography revealed marked eccentric thickening of the subepithelium and normal thickness of the stroma. We proceeded with silicone oil removal and intraocular and anterior chamber lavage at first, followed by epithelial lesion excision combined with amniotic membrane transplantation 3 months later. The patient was satisfied with the clear cornea appearance.

Effect of Adjunctive Intravitreal Conbercept Injection at the End of 25G Vitrectomy on Severe Proliferative Diabetic Retinopathy: 6-Month Outcomes of a Randomised Controlled Trial.

INTRODUCTION: This study aimed to evaluate the effect of pre-operative versus pre-operative plus post-operative intravitreal conbercept (IVC) injection on severe proliferative diabetic retinopathy (PDR). METHODS: This was a prospective, comparative and randomised study. A total of 84 patients who underwent vitrectomy for severe PDR were included in this study. Patients were randomly divided into control (41 eyes) and experiment (43 eyes) groups. Patients in the experiment group received adjunctive pre-operative and post-operative IVC injection, whereas patients in the control group only received pre-operative IVC injection. The incidence of post-operative vitreous haemorrhage (POVH), best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were determined. RESULTS: The incidence of early POVH was significantly different between the two groups, but no significant difference was observed between groups at 3 and 6 months. In the experiment group, the BCVA was significantly improved 1 month after surgery when compared with the control group (p 0.019). There was no marked difference in the mean post-operative BCVA at 3 and 6 months between groups (p 0.063 and 0.082). CRT was significantly lower in the experiment group than in the control group at 1 and 3 months after surgery (p 0.037 and 0.041), but there was no significant difference at 6 months (p 0.894). CONCLUSION: Additional IVC injected at the end of surgery improves the POVH and BCVA at the early stage after surgery in severe PDR, but this benefit is absent at 6 months. Further studies are needed to investigate the effect of IVC at the end of vitrectomy. TRIAL REGISTRATION: chictr.org.cn identifier: ChiCTR2200060735. Retrospectively registered, register date: 9 June 2022.

BMI and plasma lipid levels with risk of proliferative diabetic retinopathy: a univariable and multivariable Mendelian randomization study.

Background: The study aimed to determine whether a causal effect exists between body mass index (BMI) or plasma lipid levels and proliferative diabetic retinopathy (PDR) risk in humans. Methods: We utilized univariable (UVMR) and multivariable two-sample Mendelian randomization (MVMR) analyses to confirm the effects of BMI and plasma lipid levels on the risk of PDR. Genetic variants associated with BMI and three plasma lipids were obtained from GWAS summary datasets generated by many different consortia and were deposited in the MR-Base database. The GWAS summary data for PDR from the FinnGen biobank included 2,12,889 participants of European ancestry (8,681 cases and 2,04,208 controls). Inverse variance weighted (IVW) was applied as the main MR analysis. Sensitivity analysis was used to evaluate the robustness of our findings. Results: In the UVMR analysis, the causal associations of genetically predicted BMI with PDR presented a positive association (OR = 1.120, 95% CI = 1.076-1.167, P < 0.001), and the lower HDL-C level was associated with a higher risk of PDR (OR = 0.898, 95% CI = 0.811-0.995, P = 0.040). No evidence of an association between LDL-C or TG levels (P > 0.05) and PDR risk was found. In the MVMR analysis controlling for the HDL-C level, there was strong evidence for a direct causal effect of BMI on the risk of PDR (OR = 1.106, 95%CI = 1.049, 1.166, P < 0.001, IVW). After adjusting for BMI, there was no evidence for a direct causal effect of the HDL-C level on the risk of PDR (OR = 0.911, 95% CI = 0.823, 1.008, P = 0.072). Sensitivity analyses confirmed that the results were reliable and stable. Conclusion: Robust evidence was demonstrated for an independent, causal effect of BMI in increasing the risk of PDR. Further studies are required to understand the potential biological mechanisms underlying this causal relationship.

Changing Trends in the Disease Burden of Cataract and Forecasted Trends in China and Globally from 1990 to 2030.

Aim: To explore the trends in the prevalence and disease burden of cataract from 1990 to 2019, evaluate attributable risk factors, and predict trends over the next decade in China and globally. Methods: Data was obtained from Global Burden of Disease Study 2019. We calculated the age-standardized prevalence rate (ASR) and annual percentage change (EAPC) to show the trends of cataract in China and different regions. We calculated and reported the proportion of disability adjusted life years (DALYs) attributable to risk factors by sex in China and different regions. Then, the Bayesian age-period-cohort (BAPC) analysis model was also used to predict the prevalence trends from 2020 to 2030 in China and globally. Results: The ASR increased from 867.09 in 1990 to 991.56 in 2019 per 100,000 with an EAPC of 0.88 in China. The age-standardized DALY rate of females was higher than males. DALY rates were correlated to household air pollution from solid fuels, tobacco, high fasting plasma glucose and high body-mass index. The projective model indicates that the ASR for cataracts will rise to 1101.35×106 for male and 1616.63×106 for female by 2030. Conclusion: The trends from 1990 to 2030 suggested that the burden of cataract remains high in China. Maintaining good lifestyle habits such as switching to clean energy, reducing cigar intake, controlling blood glucose and weight can reduce the risk of cataracts. As aging increases, China should pay more attention to cataract-induced low vision and blindness and develop public policies to reduce the disease burden.

A cross-sectional study of retinal vessel changes based on optical coherence tomography angiography in Alzheimer's disease and mild cognitive impairment.

Background: The involvement of retina and its vasculature has been recently described in Alzheimer's disease (AD). Optical coherence tomography angiography (OCTA) is noninvasively used to assess the retinal blood flow. Objective: This study was to compare vessel density (VD) and blood perfusion density (PD) of the macular in AD patients, mild cognitive impairment (MCI) patients and healthy controls by OCTA, which may provide new ideas for diagnosis of AD or MCI. Methods: AD patients, MCI patients and healthy controls underwent a comprehensive ophthalmic and neurological evaluations, including cognitive function assessments as well as visual acuity, intraocular pressure (IOP), slit lamp examinations, and OCTA. General demographic data, cognitive function, retinal VD and PD were compared among three groups. The correlations among retinal VD, PD and cognitive function, amyloid-beta (Aß) protein and phosphorylated Tau (p-Tau) protein were further evaluated. The correlations between retinal superficial capillary plexus and cognitive function, Aß protein and p-Tau protein were also explored. Results: A total of 139 participants were recruited into this study, including 43 AD patients, 62 MCI patients, and 34 healthy controls. After adjusting for sex, age, history of smoking, history of alcohol intake, hypertension, hyperlipidemia, best corrected visual acuity, and IOP, VD and PD in the nasal and inferior regions of the inner ring, superior and inferior regions of outer ring in the AD group were significantly lower than in the control group (p < 0.05). PD in nasal region of outer ring also significantly decreased in the AD group. VD and PD in superior and inferior regions of inner ring, superior and temporal regions of outer ring in the MCI group were markedly lower than in the control group (p < 0.05). After adjusting for sex and age, VD and PD were correlated with Montreal Cognitive Assessment Basic score, Mini-mental State Examination score, visuospatial function and executive function (p < 0.05), while Aß protein and p-Tau protein had no relationship with VD and PD. Conclusion: Our findings suggest that superficial retinal VD and PD in macula may be potential non-invasive biomarkers for AD and MCI, and these vascular parameters correlate with cognitive function.

Cysteamine hydrochloride affects ocular development and triggers associated inflammation in zebrafish.

The increasing use of cosmetics has raised widespread concerns regarding their ingredients. Cysteamine hydrochloride (CSH) is a newly identified allergenic component in cosmetics, and therefore its potential toxicity needs further elucidation. Here, we investigated the in vivo toxicity of CSH during ocular development utilizing a zebrafish model. CSH exposure was linked to smaller eyes, increased vasculature of the fundus and decreased vessel diameter in zebrafish larvae. Moreover, CSH exposure accelerated the process of vascular sprouting and enhanced the proliferation of ocular vascular endothelial cells. Diminished behavior in response to visual stimuli and ocular structural damage in zebrafish larvae after CSH treatment were confirmed by analysis of the photo-visual motor response and pathological examination, respectively. Through transcriptional assays, transgenic fluorescence photography and molecular docking analysis, we determined that CSH inhibited Notch receptor transcription, leading to an aberrant proliferation of ocular vascular endothelial cells mediated by Vegf signaling activation. This process disrupted ocular homeostasis, and induced an inflammatory response with neutrophil accumulation, in addition to the generation of high levels of reactive oxygen species, which in turn promoted the occurrence of apoptotic cells in the eye and ultimately impaired ocular structure and visual function during zebrafish development.