ASSOCIATION BETWEEN RETINAL PIGMENT EPITHELIUM TEAR AND ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY: A Systematic Review and Meta-Analysis.

PURPOSE: To identify the prevalence of retinal pigment epithelium tear (RPET) after anti-vascular endothelial growth factor (VEGF) therapy and determine the efficacy of continued anti-VEGF therapy in patients with RPET. METHODS: All relevant clinical trials and observational studies in several online databases were screened. The main outcomes were the incidence of RPET after anti-VEGF therapy and changes in visual acuity for patients with RPET treated with continued anti-VEGF. RESULTS: The pooled incidence of RPET after anti-VEGF therapy from 24 studies with 17,354 patients was 1.9% (95% CI: 1.3-2.7). Most new RPET cases were concentrated in the first month at baseline or after the first injection during anti-VEGF therapy and gradually decreased by the subsequent month or injection. 13 studies with 157 patients reported that for patients who received anti-VEGF therapy after RPET, their pooled best-corrected visual acuity improved, but did not reach a significant level (standardized mean differences 0.34; 95% CI: -0.03 to 0.71). CONCLUSION: The incidence of RPET after anti-VEGF therapy is low. The intravitreal anti-VEGF injection may accelerate this process. For patients with RPET, maintenance of anti-VEGF therapy ensures visual acuity stability.

Knockdown of ChREBP ameliorates retinal microvascular endothelial cell injury and angiogenic responses in diabetic retinopathy.

PURPOSE: To examine whether and how carbohydrate response element-binding protein (ChREBP) plays a role in diabetic retinopathy. METHODS: Western blotting was used to detect ChREBP expression and location following high glucose stimulation of Human Retinal Microvascular Endothelial Cells (HRMECs). Flow cytometry, TUNEL staining, and western blotting were used to evaluate apoptosis following ChREBP siRNA silencing. Cell scratch, transwell migration, and tube formation assays were used to determine cell migration and angiogenesis. Diabetic models for wild-type (WT) and ChREBP knockout (ChKO) mice were developed. Retinas of WT and ChKO animals were cultivated in vitro with vascular endothelial growth factor + high glucose to assess neovascular development. RESULTS: ChREBP gene knockdown inhibited thioredoxin-interacting protein and NOD-like receptor family pyrin domain containing protein 3 expression in HRMECs, which was caused by high glucose stimulation, reduced apoptosis, hindered migration, and tube formation, and repressed AKT/mTOR signaling pathway activation. Compared with WT mice, ChKO mice showed suppressed high glucose-induced alterations in retinal structure, alleviated retinal vascular leakage, and reduced retinal neovascularization. CONCLUSIONS: ChREBP deficiency decreased high glucose-induced apoptosis, migration, and tube formation in HRMECs as well as structural and angiogenic responses in the mouse retina; thus, it is a potential therapeutic target for diabetic retinopathy.

Crocetin inhibits choroidal neovascularization in both in vitro and in vivo models.

Choroidal neovascularization (CNV) is the primary pathogenic process underlying wet age-related macular degeneration, leading to severe vision loss. Despite current anti-vascular endothelial growth factor (VEGF) therapies, several limitations persist. Crocetin, a major bioactive constituent of saffron, exhibits multiple pharmacological activities, yet its role and mechanism in CNV remain unclear. Here, we investigated the potential effects of crocetin on CNV using in vitro and in vivo models. In human umbilical vein endothelial cells, crocetin demonstrated inhibition of VEGF-induced cell proliferation, migration, and tube formation in vitro, as assessed by CCK-8 and EdU assays, transwell and scratch assays, and tube formation analysis. Additionally, crocetin suppressed choroidal sprouting in ex vivo experiments. In the human retinal pigment epithelium (RPE) cell line ARPE-19, crocetin attenuated cobalt chloride-induced hypoxic cell injury, as evidenced by CCK-8 assay. As evaluated by quantitative PCR and Western blot assay, it also reduced hypoxia-induced expression of VEGF and hypoxia-inducible factor 1α (HIF-1α), while enhancing zonula occludens-1 expression. In a laser-induced CNV mouse model, intravitreal administration of crocetin significantly reduced CNV size and suppressed elevated expressions of VEGF, HIF-1α, TNFα, IL-1ß, and IL-6. Moreover, crocetin treatment attenuated the elevation of phospho-S6 in laser-induced CNV and hypoxia-induced RPE cells, suggesting its potential anti-angiogenic effects through antagonizing the mechanistic target of rapamycin complex 1 (mTORC1) signaling. Our findings indicate that crocetin may hold promise as an effective drug for the prevention and treatment of CNV.

Preoperative estimation of retinal hole location using ultra-wide-field imaging.

BACKGROUND/OBJECTIVE: Accurate localization of retinal holes is essential for successful scleral buckling (SB) surgery. We aimed to verify the feasibility of using ultra-wide-field (UWF) imaging for preoperative estimation of retinal hole location. PATIENTS AND METHODS: We observed 21 eyes from 21 patients with rhegmatogenous retinal detachment (RRD) who underwent successful SB. They were treated at the Department of Ophthalmology of the Second Hospital of Hebei Medical University between November 2020 and November 2021. UWF fundus photography using an Optos device was performed at different steering positions 1 day before, 1 day after, and 1 month after SB. Using the preoperative fundus images, we measured the transverse diameter of the optic disc (D1) and the distance from the centre of the retinal holes to the ora serrata (D2). The accurate transverse diameter of the optic disc (Dd) was measured preoperatively using optical coherence tomography. The same surgeon measured the scleral chord lengths intraoperatively from the limbus to the located retinal hole marked on the sclera using an ophthalmic calliper. Statistical software was used to analyze the consistency of scleral chord length between the retinal hole and the limbus, which was estimated by preoperative UWF imaging and was measured using an ophthalmic calliper intraoperatively. RESULTS: There was no statistically significant difference in the scleral chord length between the retinal holes and the limbus, which was estimated by preoperative UWF fundus photography and was measured by the calliper during surgery. CONCLUSION: It is feasible to locate retinal holes using UWF fundus photography before SB, which is helpful for quick localization, thereby reducing the learning curve of SB surgery.

Preoperative ultra-wide-field imaging can provide abundant information about retinal holes and is helpful for assessing their location before surgery.In this prospective cohort study of 21 patients, 25 retinal holes in four quadrants were observed.Axial length and the position of the holes have little impact on preoperative ultra-wide field imaging assessment.

Macular hole following phakic intraocular lens implantation: A case report.

BACKGROUND: Phakic intraocular lens (pIOL) implantation has been commonly prescribed and is considered as a safe and effective option for correcting high myopia. However, it is associated with multiple complications. CASE SUMMARY: This report describes a case of full-thickness macular hole (MH) in a patient with a history of bilateral pIOL implantation for the correction of myopia of -12.00 diopters in both eyes 7 mo ago. The MH closed after pars plana vitrectomy with internal limiting membrane removal and the best-corrected visual acuity improved to 20/40 in the left eye. CONCLUSION: In rare cases, MH can occur following pIOL. In this present case report, we analyzed the formation process of MH following the surgery and emphasized that it is important to inform highly myopic patients about the risk of MH occurrence while being aware of the symptoms of this complication.

Total venous nature of retinal deep capillary plexus inferred by continuity of prominent middle limiting membrane sign in optical coherence tomography.

This study aimed to theoretically identify the vascular nature of the deep capillary plexus (DCP) by examining patients presenting with both paracentral acute middle maculopathy (PAMM) and prominent middle limiting membrane (p-MLM) sign and p-MLM sign alone in spectral-domain optical coherence tomography (SD-OCT). A retrospective review of the medical records of patients with retinal vein or artery occlusion from two tertiary medical centers was performed. Consecutive patients with a clinical diagnosis of all categories of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) (branch or central and ischemic or non-ischemic) who had undergone SD-OCT imaging from January 2015 to May 2020 were recruited and their p-MLM signs and PAMM lesions were assessed. We included 118 patients who presented with p-MLM sign with or without PAMM lesions. Amon them, 40 were female and 78 were male, with a mean age of 61.1 years. Of the 109 patients with both p-MLM sign and PAMM lesions, 23 had branch RAO, two had branch RVO, 67 had central RAO, 13 had central RVO, and four had a combination of central RAO and central RVO. All nine patients with the p-MLM sign alone had central RVO accompanied by cystoid macular edema. In all the enrolled patients, the hyperreflective lines of the p-MLM sign were continuous, regardless of the type of PAMM lesions. In conclusion, when PAMM and p-MLM sign are examined together, further proof regarding the possible complete venous nature of the vasculature of the retinal DCP might be speculated.

Intraocular Foreign Bodies: Clinical Characteristics and Factors Affecting Visual Outcome.

OBJECTIVE: To investigate the clinical characteristics and factors affecting visual outcome in patients with intraocular foreign bodies (IOFBs) and determine the risk factors for the development of endophthalmitis. Study Design. A retrospective case-series study design was adopted. SUBJECTS: In total, 242 patients (242 eyes) who were hospitalized and underwent surgical treatment for IOFB at the Second Hospital of Hebei Medical University between January 1, 2008, and December 31, 2019, were included. METHODS: The demographic data, cause of injury, characteristics of IOFBs, postinjury ocular manifestations, and surgical details of the subjects were collected, and the factors affecting visual outcome and endophthalmitis development were analyzed. RESULTS: The most common cause of IOFBs was the propulsion of foreign bodies into the eye due to hammering (149 cases, 61.57%), followed by foreign body penetration (57 cases, 23.55%). Most of the subjects were young adult men who sustained injuries in the work environment. Poorer visual outcomes were found in subjects with initial presenting symptoms visual acuity (PVA) < 0.1, largest IOFB diameter ≥ 3 mm, IOFBs located in the posterior segment, wound length > 5 mm, entrance wound length larger than the largest IOFB diameter, concomitant retinal detachment, concomitant vitreous hemorrhage, concomitant endophthalmitis, and concomitant proliferative vitreoretinopathy (PVR). Factors related to the development of endophthalmitis included lens capsule rupture, time of stage 1 repair surgery ≥ 24 h after trauma, removal of IOFBs ≥ 24 h after trauma, and nonadministration of intravitreal antibiotic injection. CONCLUSION: Among patients with IOFBs, initial PVA < 0.1, entrance wound length larger than the largest IOFB diameter, concomitant endophthalmitis, and concomitant PVR were risk factors for poor visual outcomes. Lens capsule rupture was a risk factor for endophthalmitis development, and the administration of intravitreal antibiotic injection was a protective factor against endophthalmitis development.

Thioredoxin-interacting protein deficiency ameliorates diabetic retinal angiogenesis.

Diabetic retinopathy is the leading cause of blindness among working-aged adults around the world. Hyperglycemia and intraocular vascular endothelial growth factor (VEGF) over-accumulation are essential for the progression of diabetic retinopathy, which eventually results in proliferative diabetic retinopathy, characterized by pathologic angiogenesis and impaired vision. Thioredoxin-interacting protein (TXNIP) was highly induced in retinal endothelial cells under diabetic conditions. However, the role of TXNIP in diabetes-associated retinal angiogenesis remains elusive. Here, we investigated whether the absence of TXNIP alters diabetes-associated retinal angiogenesis. Exposure of human retinal microvascular endothelial cells (HRMECs) to moderately high glucose (MHG) promoted cell migration and tube formation, but not proliferation. Knockdown of TXNIP suppressed moderately high glucose (MHG)-induced reactive oxygen species (ROS) generation, migration, tube formation and activation of Akt/mTOR pathway in HRMECs. Moreover, gene silencing of TXNIP inhibited VEGF-induced angiogenic response by blocking VEGFR2 and downstream signal pathway Akt/mTOR activation in HRMECs. Furthermore, TXNIP knockout inhibited VEGF or VEGF and MHG-induced retinal angiogenesis ex vivo compared with wild-type mice. In conclusion, our study demonstrated that TXNIP deficiency inhibited VEGF or/and MHG-induced angiogenic response in HRMECs and mice retinas and suggested TXNIP may be a potential therapy target for treating proliferative diabetic retinopathy.

Sphingosine kinase 1 protects renal tubular epithelial cells from renal fibrosis via induction of autophagy.

Autophagy is an important homoeostatic mechanism for the lysosomal degradation of protein aggregates and damaged cytoplasmic components. Recent studies suggest that autophagy which is induced by TGF-ß1 suppresses kidney fibrosis in renal tubular epithelial cells (RTECs) of obstructed kidneys. Sphingosine kinase 1(SK1), converting sphingosine into endogenous sphingosine-1-phosphate (S1P), was shown to modulate autophagy and involved in the processes of fibrotic diseases. Since SK1 activity is also up-regulated by TGF-ß1, we explored its effect on the induction of autophagy and development of renal fibrosis in this study. In vitro, SK1 expression and activity were markedly increased by TGF-ß1 stimulation in a time and concentration dependent manner, and concomitant changes in autophagic response were observed in HK-2 cells. Further, knockdown of SK-1 led to a decrease of autophagy whereas overexpression of SK1 caused a greater induction of autophagy. In addition, overexpression of SK1 resulted in decreased of mature TGF-ß levels through autophagic degradation. In vivo, SK1 enzymatic activity and autophagic response were both up-regulated in a mouse model of kidney fibrosis induced by unilateral ureteral obstruction (UUO); meanwhile, increased of mature TGF-ß1 and deposition of extracellular matrix (ECM) were observed in tubulointerstitial areas compared with sham-operated mice. However, aggravation of renal fibrosis was detected when SK1 inhibitor PF-543 was applied to suppress SK1 enzymatic activity in UUO mice. At the same time, autophagy was also inhibited by PF-543. Thus, our findings suggest that SK1 activation is renoprotective via induction of autophagy in the fibrotic process.