Minimal effect of sleep on the risk of age-related macular degeneration: a Mendelian randomization study.

Aims: Observational studies have shown that sleep pattern is associated with age-related macular degeneration (AMD), but whether sleep pattern is a causal factor for AMD remains unclear. This study aims to use Mendelian randomization (MR) analysis to investigate the potential causal relationship between sleep traits and AMD. Methods: This is a two-sample MR study. The single-nucleotide polymorphisms associated with AMD and early AMD were selected as the outcome from two different genome-wide association studies (GWAS): the early AMD GWAS with 14,034 cases and 91,214 controls, and AMD GWAS with 3,553 cases and 147,089 controls. The datasets of sleep duration, daytime dozing, and sleeplessness were used as exposure, which comprised nearly 0.46 million participants. Inverse-variance weighted method was used as the main result, and comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the impact of potential horizontal pleiotropy. Results: Through MR analysis, we found that sleep duration was significantly associated with AMD (OR = 0.983, 95% CI = 0.970-0.996, P-value = 0.01). We also found suggestive evidence for the association of genetically predicted sleep duration with early AMD, which showed a consistent direction of effect with a marginal significance (OR = 0.724, 95% CI = 0.503-1.041, P-value = 0.08). Sensitivity analyses further supported the robustness of the causal relationship between sleep duration and AMD. However, we were unable to determine the relationship between daytime dozing or sleeplessness and AMD (including early AMD) (P-value > 0.05). Conclusion: Sleep duration affects the causal risk for AMD; that is, longer sleep duration reduces the risk of AMD, while shorter sleep duration increases the risk of AMD. Although the influence is minimal, keeping adequate sleep duration is recommended, especially for patients with intermediate or advanced AMD.

A sutureless technique for securing leaking sclerotomies with viscoelastic substances in 23-gauge microincision vitrectomy surgery.

AIM: To introduce and evaluate the clinical efficacy of a new technique, the use of viscoelastic substances (VS) to close leaking sclerotomy in 23G microincision vitrectomy, and to observe its effect on the visual acuity and intraocular pressure (IOP) of patients. METHODS: Patients who underwent 23G vitrectomy in Ningbo Eye Hospital before the use of VS technique (June 2019 to September 2020) and after the use of VS technique (October 2020 to December 2021) were selected as the subjects of this study. The above cases underwent operation by the same surgeon and were retrospectively analyzed. VS technique was used as the alternative to suturing, in which a small amount of VS was injected at the leaking sclerotomy and then gently massaged to confirm leaking sclerotomy closure. RESULTS: A total of 174 eyes were covered in the study, including 84 eyes in the control group (before the use of VS technique) and 90 eyes in the VS technique group. The number of eyes that needed to be sutured decreased considerably from 42.9% in the control group to 3.3% in the VS technique group, and the proportion of subconjunctival hemorrhage at 1-2d after surgery decreased remarkably from 35.7% in the control group to 2.2% in the VS technique group. No substantial differences in the incidence of mean IOP and low IOP were found between 1-2 and 3-20d after surgery in the VS technique group. No major complications associated with VS technique were identified during the study. CONCLUSION: In 23G microincision vitrectomy, VS technique is a safe, simple, and effective method to close leaking sclerotomy.

Nintedanib induces apoptosis in human pterygium cells through the FGFR2-ERK signalling pathway.

AIM: To investigate whether nintedanib can inhibit pterygium cells through the fibroblast growth factor receptor 2 (FGFR2)/extracellular-signal-regulated kinase (ERK) pathway. METHODS: Human primary pterygium cells were cultured in vitro. After treatment with nintedanib, the cell morphology was observed under microscopy, the morphological changes of the nucleus were observed after DAPI staining, apoptosis was analyzed by Annexin-V FITC/PI double staining, and the changes of apoptosis-associated proteins were detected by Western blot. The binding ability of nintedanib to FGFR2 was predicted by molecular docking. Finally, by silencing FGFR2, we explored whether nintedanib inhibited FGFR2/ERK pathway. RESULTS: The results showed that nintedanib inhibited the growth of pterygium cells and caused nuclear pyknosis. The results of Annexin-VFITC/PI double staining showed that nintedanib was able to induce early and late apoptosis of pterygium cells, significantly increasing the expression of apoptosis-associated proteins Bax and cleaved-Caspase3 (P<0.05), and reducing the expression of Bcl-2 (P<0.05). In addition, nintedanib significantly inhibited ERK1/2 phosphorylation through FGFR2 (P<0.05). After silencing the expression of FGFR2, there was no significant difference in the inhibition of ERK1/2 phosphorylation by nintedanib (P>0.05). CONCLUSION: Nintedanib induces apoptosis of pterygium cells by inhibiting FGFR2/ERK pathway.

Causal Relationships Between Glycemic Traits and Myopia.

Purpose: Little is known about whether sugar intake is a risk factor for myopia, and the influence of glycemic control remains unclear, with inconsistent results reported. This study aimed to clarify this uncertainty by evaluating the link between multiple glycemic traits and myopia. Methods: We employed a two-sample Mendelian randomization (MR) design using summary statistics from independent genome-wide association studies. A total of six glycemic traits, including adiponectin, body mass index, fasting blood glucose, fasting insulin, hemoglobin A1c (HbA1c), and proinsulin levels, were used as exposures, and myopia was used as the outcome. The inverse-variance-weighted (IVW) method was the main applied analytic tool and was complemented with comprehensive sensitivity analyses. Results: Out of the six glycemic traits studied, we found that adiponectin was significantly associated with myopia. The genetically predicted level of adiponectin was consistently negatively associated with myopia incidence: IVW (odds ratio [OR] = 0.990; P = 2.66 × 10-3), MR Egger (OR = 0.983; P = 3.47 × 10-3), weighted median method (OR = 0.989; P = 0.01), and weighted mode method (OR = 0.987; P = 0.01). Evidence from all sensitivity analyses further supported these associations. In addition, a higher HbA1c level was associated with a greater risk of myopia: IVW (OR = 1.022; P = 3.06 × 10-5). Conclusions: Genetic evidence shows that low adiponectin levels and high HbA1c are associated with an increased risk of myopia. Given that physical activity and sugar intake are controllable variables in blood glycemia treatment, these findings provide new insights into potential strategies to delay myopia onset.

Single-string, closed-loop fixation modification to reposit a dislocated triple-looped haptic intraocular lens.

A technique using the single-string, closed-loop fixation method to reposit dislocated triple-looped haptic intraocular lens (IOL)-capsular bag complex is described. The long needle or curved needle with a 10-0/8-0 polypropylene suture and a 27/30-gauge needle were used as the guide needle to pass through the fenestrated haptics twice. The scleral interlaminar course was used as the fixed point. Last, a fixation knot was created in the sclerotomy by the 2 ends of the thread to close the suture loop for IOL fixation. Another knot was created about 2 to 3 mm from the exit point and was intrasclerally anchored by the aid of the attached needle. 4 eyes from 4 consecutive patients were studied retrospectively; during all follow-up visits, the IOLs were well centered and stable, and no suture erosion, hypotony, scleral atrophy, chronic inflammation, retinal tears, and/or detachments were observed.

Changes of plasma nitric oxide, endothelin-1, and blood coagulation following intravitreal conbercept.

Intravitreal anti-VEGF (anti-vascular endothelial growth factor) biologics have revolutionized the pharmacological management of chorioretinal diseases. However, the systemic adverse events such as stroke or bleeding are the concerns for many patients and physicians. The mechanism to develop these side effects are poorly understood. Consecutive 95 patients with retinal diseases were studied for their blood activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), and concentration of fibrinogen before and after intravitreal conbercept. Additionally, plasma nitric oxide (NO) and endothelin-1 (ET-1) were investigated on 38 of the 95 patients. Compared with the pre-injection, 4-week post-injection values of APTT and PT were increased by 0.582 s (p = 0.038, paired t test) and by 0.086 s (p = 0.080, paired t test; p = 0.0475, Sign test), respectively. At the same time, fibrinogen decreased by 0.048 g/L. Plasma levels of NO or ET-1 or VEGF did not significantly change from pre-injection levels. Our findings advanced the understanding of mechanism for systemic side effects associated with intravitreal anti-VEGF and emphasized paying more attention to higher risk of possible bleedings for patients following intravitreal conbercept.

Autologous tenon capsule packing to treat posterior exit wound of penetrating injury: A case report.

BACKGROUND: This study reports a case of autologous tenon capsule packing to treat the posterior exit wound of penetrating injury. CASE SUMMARY: To treat a 58-year-old male patient with penetrating eyeball injury caused by an iron sheet, we used autologous tenon capsule packing. Two months after removal of the silicone oil, the corrected visual acuity was 0.3, the retina was flat, the tenon capsule graft was in place, the posterior wound closed well, and the intraocular pressure was 15.8 mmHg. CONCLUSION: Autologous tenon capsule packing to treat the posterior exit wound of penetrating injury is safe and effective.

Scleral Buckling with Viscoelastics or Gas Injection for Bulging Retinal Detachments: A Retrospective Cohort Study.

OBJECTIVE: To examine the use of a viscoelastic agent instead of air in the vitreous cavity during surgery for scleral buckling. METHODS: This was a retrospective cohort study of patients who underwent scleral buckling surgery for bulging rhegmatogenous retinal detachment (RRD) at Ningbo Eye Hospital from 07/2016 to 12/2019. The patients were grouped into drainage, air injection, cryotherapy and explant (DACE) and drainage, viscoelastic injection, cryotherapy, and explant (DVCE) groups, which were comparatively assessed. RESULTS: There were 25 and 22 patients in the DVCE and DACE groups, respectively. The surgery was significantly shorter with DVCE than DACE (P < 0.05), with less intraoperative external pressure adjustment (P < 0.05). BCVA was lower in the DVCE group at 1 week compared with the DACE group (P < 0.05). Successful retinal reattachment was observed in 92.0% and 81.8% of the DVCE and DACE groups, respectively (P < 0.05). Cases requiring laser replenishing after the operation were less in the DVCE group compared with the DACE group (P < 0.05). There were no differences in complications and intraocular pressure between the two groups (all P < 0.05). CONCLUSION: DVCE has better operative characteristics and faster vision recovery than DACE, with similar outcomes.

Implication of inflammatory cytokines in the aqueous humour for management of macular diseases.

PURPOSE: To characterize profile of cytokines in aqueous humour of common macular diseases during intravitreal anti-VEGF therapy. METHODS: Aqueous humour from eyes with central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), diabetic macular oedema (DME), neovascular age-related macular degeneration (nAMD) or pathologic myopia associated choroidal neovascularization (pmCNV) was sampled prior to 1st (n = 144) and 2nd (n = 48) intravitreal anti-VEGF therapy. Cytokines including vascular endothelium growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1) and interleukin 6 (IL-6) were quantitated and analysed along with retinal thickness data by optical coherence tomography (OCT) across two intravitreal injections and five macular disease types. RESULTS: ICAM-1, IL-6 and VEGF are positively associated in the aqueous humour of naive eyes (r = 0.39-0.77, p = 0.018 to <0.0001). ICAM-1, VEGF and IL-6 were significantly higher in CRVO and DME while lowest in pmCNV (p < 0.0001). Reduction of central retinal thickness (CRT) as a favourable response to anti-VEGF therapy was in the order of CRVO, BRVO, DME and nAMD/pmCNV (p < 0.0001). The strongest predictor for favourable CRT reduction was baseline CRT (p < 0.0001) followed by baseline ICAM-1 (p = 0.04). After the 1st intravitreal anti-VEGF therapy, VEGF in aqueous humour lowered significantly but ICAM-1 and IL-6 levels remained unchanged. ICAM-1 was not predictive for CRT reduction following 2nd anti-VEGF therapy. CONCLUSION: Rate of cytokine production is disease-dependent and higher in CRVO and DME. Anatomical response to intravitreal anti-VEGF therapy is disease-specific and best in RVO patients. A combination therapy using both anti-VEGF and anti-inflammatory therapeutics may be superior to single anti-VEGF therapy, at least for RVO and DME.

Cyclophotocoagulation with an illuminated laser probe under a noncontact wide-angle retinoscope: A modified technique of ciliary body photocoagulation.

PURPOSE: This study aimed to investigate the efficacy of cyclophotocoagulation with an illuminated laser probe under a noncontact wide-angle retinoscope in treating refractory glaucoma. METHODS: Eleven patients (11 eyes) with refractory neovascular glaucoma were treated with ciliary body photocoagulation. Preoperative and postoperative corrected visual acuity, intraocular pressure (IOP), ophthalmofundoscopy, B-ultrasound and ultrasound biomicroscopy, optical coherence tomography, and fundus fluorescein angiography were performed. RESULTS: Preoperative IOP ranged from 45 to 58 mmHg (mean 51.9 mmHg). At postoperative 1, 3, and 6 months, the IOPs ranged between 16 and 33 mmHg (mean 27.1 mmHg), 14-28 mmHg (mean 20.6 mmHg), and 14-28 mmHg (mean 18.5 mmHg), respectively. IOP at the last follow-up (range 7-12 months) was 15-24 mmHg (mean 18.8 mmHg). An average of 63.8% decrease in postoperative IOP was found in these patients with no associated complications. The postoperative fibrotic exudate, anterior chamber hyphema, and exudative choroidal detachment were all well-managed and resolved. No patients experienced intraocular lens deviation or dislocation, hypotonia oculi, atrophy of eyeball, retinal detachment, endophthalmitis, or sympathetic ophthalmia. CONCLUSION: Cyclophotocoagulation with an illuminated laser probe under a noncontact wide-angle retinoscope is a safe and effective technique for the treatment of neovascular glaucoma.

Managing dislocated hard lens nuclei: 23-gauge vitrectomy and lens extraction via a corneoscleral limbal incision versus 23-gauge vitrectomy and phacofragmentation.

PURPOSE: To compare 23-gauge vitrectomy and lens extraction via a corneoscleral limbal incision (CSLI) with 23-gauge vitrectomy and phacofragmentation to treat dislocation of hard lens nuclei. SETTING: Ningbo Eye Hospital, Zhejiang, China. DESIGN: Retrospective case series. METHODS: The study included consecutive patients with complete posterior dislocation of a hard nucleus (grade ≥ IV) into the vitreous cavity. All patients received 23-gauge 3-channel vitrectomy. Some patients also had phacofragmentation and others had lens extraction through a CSLI. RESULTS: The CSLI group comprised 21 eyes of 21 patients and the phacofragmentation group, 22 eyes of 22 patients. The median follow-up was 10.8 months (range 6 to 24 months) and 11.3 months (range 5 to 18 months), respectively. Demographic characteristics, reason for lens dislocation, preoperative corrected distance visual acuity (CDVA), preoperative intraocular pressure (IOP), lens nucleus grade, and comorbidities were similar between groups. The CSLI group had a shorter mean surgical time than the phacofragmentation group (42.5 ± 7.2 minutes versus 68.2 ± 16.5 minutes); less frequent use of perfluorocarbon liquid, octafluoropropane, or air tamponade; lower incidence of retinal tears (9.5% versus 31.8%); and better CDVA but worse astigmatism 1 day and 1 week postoperatively (P < .05). The postoperative IOP did not differ between groups. Corneal edema and recurrent retinal detachment were less common in the CSLI group than in the phacofragmentation group. CONCLUSION: The 23-gauge vitrectomy with lens extraction through a CSLI might have advantages over 23-gauge vitrectomy with phacofragmentation for management of dislocated hard lens nuclei.

Unilateral endogenous fungal endophthalmitis after esophageal cancer surgery: a case report.

BACKGROUND: This study reports a case of Unilateral Endogenous Fungal Endophthalmitis After Esophageal Cancer Surgery. CASE PRESENTATION: One patient presented with a month-long loss of vision in his left eye, he had surgery for esophageal cancer 2 months earlier. The patient underwent cataract surgery (by phacoemulsification) in the left eye combined with 25-gauge vitrectomy and silicone oil tamponade. The microbiological culture pointed to infection with Candida albicans. At 3-month follow-up, the unaided visual acuity of left eye was 0.02 and corrected visual acuity was 0.2. In addition, there was no recurrence of the endophthalmitis within 1 year of the surgery. CONCLUSION: The early diagnosis of endogenous fungal endophthalmitis is difficult, and the disease is very likely to be misdiagnosed as uveitis. It is therefore critical to improve awareness of this condition and to reduce the incidence of its misdiagnosis.

HSV­TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK.

Retinoblastoma is an severe ophthalmic disease and the most common type intraocular malignant tumor, particularly in infants. Currently, few drugs and therapies are available. Gene therapy has been considered to be a potential treatment to cure cancer effectively and Herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV­TK/GCV) is one type of suicide gene therapy that has been extensively studied. Numerous in vitro and in vivo studied have shown that this system can kill tumor cells, including liver and lung cancer cells. GCV is used as an antiviral drug, and the thymidine kinase, HSV­TK can phosphorylate GCV to GCV­TP, a competitive inhibitor of DNA synthesis, instead of guanine­5'­triphosphate in the process of DNA synthesis. This process prevents DNA chain elongation causing cell death via apoptosis. However, the toxic effects of HSV­TK/GCV on retinoblastoma cells remain unknown, and the molecular mechanisms of its therapeutic effects have not been fully elucidated. Our results suggest that HSV­TK/GCV can significantly cause the death of retinoblastoma cell lines, HXO­RB44 and Y79. Further studies have reported that this cell death is induced by the inhibition of autophagy by activating the MAPK/ERK (mitogen­activated protein kinase/ERK) signaling pathway. The mTOR inhibitor Torin1 can partially block the toxic effects of HSV­TK/GCV on HXO­RB44 cells. The above results demonstrate that the mechanism undertaken by HSV­TK/GCV to exhibit therapeutic effects mechanism may inhibit autophagy by activating MAPK/ERK. The findings of the present study may provide novel insight for the exploration of HSV­TK/GCV in the treatment of retinoblastoma.

Metformin inhibits development of diabetic retinopathy through inducing alternative splicing of VEGF-A.

Previous studies have shown that metformin, an AMP-activated protein kinase activator widely prescribed for type 2 diabetes, is especially beneficial in cases of diabetic retinopathy (DR) with undetermined mechanisms. Here, we used a streptozotocin-induced diabetes model in mice to study the effects of metformin on the development of DR. We found that 10 weeks after STZ treatment, DR was induced in STZ-treated mice, regardless treatment of metformin. However, metformin alleviated the DR, seemingly through attenuating the retina neovascularization. The total vascular endothelial cell growth factor A (VEGF-A) in eyes was not altered by metformin, but the phosphorylation of the VEGF receptor 2 (VEGFR2) was decreased, which inhibited VEGF signaling. Further analysis showed that metformin may induce VEGF-A mRNA splicing to VEGF120 isoform to reduce its activation of the VEGFR2. These findings are critical for generating novel medicine for DR treatment.

Mitochondrial transfer RNA variants and primary congenital glaucoma.

Variants in mitochondrial DNA (mtDNA) are the most important causes for vision loss, the mt-tRNA variants being the largest group among them. In this study, we report the molecular characterization of 15 mt-tRNA variants with primary congenital glaucoma (PCG). Based on phylogenetic approach, we found that only half of them were definitely pathogenic with PCG, other mutations were single nucleotide polymorphisms (SNP) in human population. Thus, our study provided novel insight into the pathogenesis of PCG.