A novel approach for 25-gauge transconjunctival sutureless vitrectomy to evaluate vitreous substitutes in rabbits.

AIM: To improve the standard three-port vitrectomy for establishing and evaluating an endotamponade model in rabbits. METHODS: Three ports were prepared near the third eyelid of rabbits, and the infusion port was placed at the inferior nasal quadrant with the inserted cannula linking with a self-designed handheld rigid infusion catheter. All right eyes of rabbits underwent a modified 25-gauge vitrectomy and were subsequently filled with balanced salt solution, silicone oil, and eight-arm polyethylene glycols (8-arm PEGs) hydrogel separately for comparison. Ophthalmic examinations were performed regularly to record the changes after the surgery. RESULTS: Successful vitrectomy was achieved among 44 chinchilla rabbits. The mean operation time was 4.51±1.25min. Four eyes (9.1%) presented limited lens touch and two eyes (4.5%) showed retinal touch during surgery. Incision leakage was found in three eyes (6.8%) after surgery. There was no endophthalmitis, hemorrhage, or retinal detachment during the observation period and ophthalmic examinations after the implantation of vitreous substitutes. CONCLUSION: The modified technique of the standard vitrectomy applied in the endotamponade model in rabbits shows excellent safety and practicality.

Phenotypic characterization of autosomal dominant progressive cone dystrophies associated with a heterozygous variant c.2512C>T of GUCY2D gene in a large kindred.

PURPOSE: In this study, we described a large family presenting different manifestations of cone dystrophy at different ages associated with GUCY2D gene mutation. METHOD: Sixty-three individuals of a single kindred, including 23 affected with cone dystrophies, were recruited and received ocular examinations, including best corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, color fundus photograph (CFP), fundus autofluorescence, optical coherence tomography, fluorescence fundus angiography, color vision testing, full-field electroretinography, and electro-oculogram. Whole exome sequencing (WES) and Sanger sequencing were performed for underlying mutations associated with cone dystrophy. RESULT: There were 23 affected family members. Clinical analysis showed that the proband and other patients had impaired visual acuity ranging from 20/800 to 20/50 with impaired color vision. Fundus photograph showed retinal pigment epithelium (RPE) granular abnormalities with depressed macular reflex in young patients and macular or retinochoriodal atrophy in older patients. OCT examination confirmed the reduced outer retinal thickness or inner retinal thickness, absence of the ellipsoid zone (EZ) and retinal atrophy to varying degrees. Electroretinography revealed a reduced cone response combined with a relatively maintained rod response. WES and Sanger sequencing revealed a heterozygous variant c.2512C>T in the GUCY2D gene of the affected family members. CONCLUSIONS: We reported cone dystrophy in 23 affected individuals in a five-generation family and demonstrated different macular abnormalities in OCT scans and CFP at different ages. The multimodal ocular records in our study provide physicians and ophthalmologists with a better understanding of cone dystrophy associated with GUCY2D mutation.

Artificial intelligence to distinguish retinal vein occlusion patients using color fundus photographs.

PURPOSE: Our aim is to establish an AI model for distinguishing color fundus photographs (CFP) of RVO patients from normal individuals. METHODS: The training dataset included 2013 CFP from fellow eyes of RVO patients and 8536 age- and gender-matched normal CFP. Model performance was assessed in two independent testing datasets. We evaluated the performance of the AI model using the area under the receiver operating characteristic curve (AUC), accuracy, precision, specificity, sensitivity, and confusion matrices. We further explained the probable clinical relevance of the AI by extracting and comparing features of the retinal images. RESULTS: Our model achieved an average AUC was 0.9866 (95% CI: 0.9805-0.9918), accuracy was 0.9534 (95% CI: 0.9421-0.9639), precision was 0.9123 (95% CI: 0.8784-9453), specificity was 0.9810 (95% CI: 0.9729-0.9884), and sensitivity was 0.8367 (95% CI: 0.7953-0.8756) for identifying fundus images of RVO patients in training dataset. In independent external datasets 1, the AUC of the RVO group was 0.8102 (95% CI: 0.7979-0.8226), the accuracy of 0.7752 (95% CI: 0.7633-0.7875), the precision of 0.7041 (95% CI: 0.6873-0.7211), specificity of 0.6499 (95% CI: 0.6305-0.6679) and sensitivity of 0.9124 (95% CI: 0.9004-0.9241) for RVO group. There were significant differences in retinal arteriovenous ratio, optic cup to optic disc ratio, and optic disc tilt angle (p = 0.001, p = 0.0001, and p = 0.0001, respectively) between the two groups in training dataset. CONCLUSION: We trained an AI model to classify color fundus photographs of RVO patients with stable performance both in internal and external datasets. This may be of great importance for risk prediction in patients with retinal venous occlusion.

Plasma and vitreous selenium concentrations in patients with type 2 diabetes and diabetic retinopathy.

BACKGROUND: This work aimed to determine and compare plasma and vitreous selenium (Se) concentrations in patients with type 2 diabetes and diabetic retinopathy (DR). METHODS: A total of 60 type-2-diabetes patients including 20 without DR, 20 with non-proliferative DR (NPDR), and 20 with proliferative diabetic retinopathy (PDR), were involved in this study. Blood plasma samples were collected from above 60 patients and 20 normal controls (without diabetes). Twenty control vitreous samples were obtained from the eyes presenting a macular hole and epimacular membrane. Vitreous samples were also collected from PDR patients receiving one-week intravitreal anti-VEGF therapy or not. Plasma and vitreous Se concentrations were determined by inductively coupled plasma mass spectrometry. RESULTS: Plasma Se concentrations in PDR patients (163.74 ±â€…32.68 µg/L) were significantly higher than those in normal control patients (121.59 ±â€…28.33 µg/L), NPDR patients (130.34 ±â€…29.11 µg/L), and the patients without DR (81.23 ±â€…20.59 µg/L) (all P < .001). Similarly, Se concentrations in vitreous samples of PDR patients (56.30 ±â€…12.03 µg/L) were consistently higher than those in control vitreous samples (26.26 ±â€…6.53 µg/L). In addition, vitreous Se concentrations in PDR patients decreased to 47.76 ±â€…9.72 µg/L after intravitreal injection of the anti-VEGF drug ranibizumab for one week, which was significantly lower than those before injection (P = .02). Plasma VEGF levels of diabetic patients were lower than those of the normal controls (P < .001). On the contrary, the vitreous VEGF level in the PDR group (913.61 ±â€…193.32 pg/mL) was significantly higher than that of the normal control group (101.23 ±â€…21.33 pg/mL) (P < .001). CONCLUSION: The elevation of Se concentrations may be an important risk factor in plasma and vitreous with diabetic retinopathy among type-2-diabetes patients. The elevated VEGF may be also closely related to the intraocular Se concentration in PDR patients.

Super-fast in situ formation of hydrogels based on multi-arm functional polyethylene glycols as endotamponade substitutes.

Polymer-based hydrogels used in the vitreous cavity could lead to an unsatisfactory gel-forming state, uncontrollable swelling, and potential cytotoxicity. Their application can significantly impair the filling effect and cause severe side effects in the surrounding tissues. To address the concerns, a poly(ethylene glycol)-engineered hydrogel capable of fast in situ gel formation (less than 1 min), with an ultralow swelling ratio and no cytotoxicity in the rabbits' eyes, was constructed as a vitreous substitute. The multi-arm polyethylene glycols (PEGs) modified with functional groups (thiol and maleimide) possess high reaction efficiency in the vitreous cavity and present excellent biomimetic characteristics of the natural vitreous humor in vitro. After injection with a double syringe via a 25-gauge needle in the eyes of rabbits for 6 months, the hydrogel functioned as an artificial vitreous body that could highly promote retinal detachment repair, with excellent biocompatibility and high transparency, and without bio-degradation or ocular complications. Collectively, the fast in situ forming hydrogel could achieve quick and good filling in the vitreous cavity without cytotoxicity, which makes it a promising long-term endotamponade substitute.

Primary intracranial papillary meningioma: Analysis of factors of prognosis and systematic review.

OBJECTIVE: Papillary meningioma is rare and displays an aggressive clinical behavior with poor prognosis. Therefore, we performed an extensive literature review to evaluate the adverse factors and treatment strategy of survival. METHOD: We performed Ovid, Medline, Embase, Pubmed, Web of Science and Cochrane database queries for articles published between 1938 and 2019 with the search term "WHO grade III meningioma" or "papillary meningioma" and "central nervous system", "cerebral", or "intracranial". RESULTS: After a careful evaluation, a total of 19 studies were included. The entire cohort included the 67 patients, 34 (50.7%) were male and 33 (49.3%) were female with a mean age of 32.6 ± 2.1 years ranging from 4.5 months to 74 years. Gross total resection was achieved in 48 (71.6%) cases, and 29 (51.8%) patients received postoperative radiation. The mean follow-up period was 42.3 ± 4.4 months (range, 2-197 months). Thirty-six (53.7%) patients happened to recurrences, 11 (16.4%) patients happened to extracranial metastasis and 25 (37.3%) patients died. Univariate analysis revealed that the MIB > 5% trended toward a shorter time to recurrence (p = 0.084). Gross total resection was associated with favorable progression-free survival (p = 0.007) and overall survival (p = 0.001). Postoperative radiation was associated with favorable progression-free survival (p = 0.001). CONCLUSIONS: Gross total resection and adjuvant radiation were recommended as the initial treatment option for patients with papillary meningioma.

Polymeric hydrogel as a vitreous substitute: current research, challenges, and future directions.

Vitreoretinal surgery is an essential approach to treat proliferative diabetic vitreopathy, retinal detachment, retinal tear, ocular trauma, and macular holes. The removal of the natural vitreous and the replacement with substitutes are critical steps for retina reattachment. Vitreous substitutes including silicone oil (SiO), air, sulfur hexafluoride (SF6), and perfluoropropane (C3F8), have been widely applied in clinical practice. However, these substitutes are reported to cause complications such as emulsification, high intraocular pressure, and lens opacification. Polymeric hydrogels are a kind of material with favorable physical, mechanical properties, and adaptable biocompatibility, thus being highly expected to be ideal vitreous substitutes. Despite years of research, very few polymeric hydrogels can be applied practically in the vitreous cavity. In this review, we focus on the development of polymeric natural-based hydrogels and synthetic hydrogels. Particularly, we pay attention to recent advances in the novel stimuli-response and self-assembly supramolecular hydrogels. Characterized by easy injectability and long residence time, this kind of hydrogel becomes the potentially promising candidates for ideal vitreous substitutes. Finally, we evaluate the current challenges and provide the future directions of vitreous substitutes.

Upregulated inflammatory associated factors and blood-retinal barrier changes in the retina of type 2 diabetes mellitus model.

AIM: To examine the expression of high mobility group box-1 (HMGB-1) and intercellular adhesion molecule-1 (ICAM-1) in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier (BRB) and blood-brain barrier (BBB) in a rat model of type 2 diabetes. METHODS: The type-2 diabetes mellitus (DM) model was established with a high-fat and high-glucose diet combined with streptozotocin (STZ). Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection (P<0.01). The serum levels of fasting insulin, Insulin resistance homeostatic model assessment (IRHOMA), total cholesterol (TC), total triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in the DM rats significantly higher than those in the controls (all P<0.01). HMGB-1 (0.96±0.03, P<0.01) and ICAM-1 (0.76±0.12, P<0.05) levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1 (0.83±0.13, P<0.01) and ICAM-1 (1.15±0.08, P<0.01) levels in the hippocampal tissues in the DM rats were also significantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls (P<0.01). However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats. CONCLUSION: BRB permeability increases significantly in rats with type-2 DM, which may be associated with the up-regulated retinal expression of HMGB-1 and ICAM-1.

A retrospective analysis of characteristics of visual field damage in patients with Leber's hereditary optic neuropathy.

The objective of this study is to investigate the characteristics and the evolution of visual field damage caused by Leber's hereditary optic neuropathy (LHON) and to provide clinical data for the diagnosis of LHON. Parameters of visual field in 32 consecutive patients (49 eyes) with LHON who were confirmed by genetic diagnostic tests were retrospectively measured within 1 week, between three to six months, and at six months after onset. Visual field defects revealed central scotoma in 26 eyes (53.1 %), paracentral scotoma in 12 eyes (24.5 %), ceco-central defects in 6 eyes (12.2 %), blind spot enlargenment in 3 eyes (6.1 %), quadrantanopia in 2 eyes (4.1 %) within 1 week after onset. After 3 to 6 months, ceco-central defects were detected in 22 eyes (44.9 %), central isopter constriction in 10 eyes (20.4 %), hemianopia or quadrantanopia in 5 eyes (10.2 %), central scotoma in 4 eyes (8.2 %), and paracentral scotoma in 1 eye (2.0 %). After 6 months, central isopter constriction was observed in 18 eyes (36.7 %), diffuse defects in 21 eyes (42.9 %), ceco-central defects in 3 eyes (6.1 %), hemianopia or quadrantanopia in 5 eyes (10.2 %), and central scotoma in 2 eyes (4.1 %). LHON at different stages was characterized by different focal visual field defects: visual field defects in LHON patients within 1 week after onset were mostly central or paracentral scotoma, which was enlarged around the ceco-central defect, or connected to form a blind spot after 3-6 months. Diffuse and central isopter constriction defects were usually developed after 6 months. Damages firstly appeared in papillomacular bundle and gradually expanded outward. These characteristics of visual field defects reported in this study might provide a clinical basis for better diagnosis of LHON.

Elevated hydrogen sulfide levels in vitreous body and plasma in patients with proliferative diabetic retinopathy.

PURPOSE: Hydrogen sulfide (H2S), a colorless gas, has been confirmed to be a gaseous messenger molecule and an endogenous stimulus for angiogenesis recently. This study was performed to investigate the role of H2S in diabetic retinopathy. METHODS: Blood samples were collected from normal controls and patients with diabetes. Vitreous samples were collected from patients with proliferative diabetic retinopathy (PDR) and patients with rhegmatogenous retinal detachment. Patients were grouped into diabetic patients without diabetic retinopathy (non-DR), with nonproliferative DR, and with PDR. Concentrations of H2S and vascular endothelial growth factor in the plasma and vitreous body were detected using a spectrophotometer. RESULTS: A decreased H2S level in the plasma was observed in non-DR group (41.89 ± 8.52 µM, P < 0.05), and an increased H2S level in the plasma was observed in PDR group (60.49 ± 11.14 µM, P < 0.001), when compared with that in normal controls (49.67 ± 9.72 µM). There was no difference in plasma H2S level between patients with nonproliferative DR (54.13 ± 8.61 µM) and normal controls. In the vitreous body, H2S levels in PDR group were significantly higher (76.80 ± 24.08 µM, P < 0.001) than that in rhegmatogenous retinal detachment group (24.37 ± 11.25 µM). Levels of vascular endothelial growth factor in plasma from patients with diabetes were significantly lower (P < 0.001) than that in normal controls. Vascular endothelial growth factor levels in the vitreous body from diabetic patients with PDR were significantly higher (885.61 ± 190.41 pg/mL, P < 0.001) than that from patients with rhegmatogenous retinal detachment (89.98 ± 19.56 pg/mL). Seven days after an intravitreal injection of ranibizumab, a significantly decreased H2S level (55.58 ± 7.20 µM, P < 0.05) was observed in the vitreous body in patients with PDR when compared with that (75.07 ± 12.95 µM) in the vitreous body collected just before intravitreal injection. CONCLUSION: These results indicated that anti-vascular endothelial growth factor may downregulate the H2S level in the vitreous body, and H2S may play a role in the development of DR. Hydrogen sulfide may be a novel target for the therapy of DR.

Involvement of HMGB1 mediated signalling pathway in diabetic retinopathy: evidence from type 2 diabetic rats and ARPE-19 cells under diabetic condition.

AIMS: Inflammation is considered to play a critical role in the pathogenesis of diabetic retinopathy, and high mobility group box protein 1 (HMGB1) could promote inflammation as an alarmin. We investigated the expression of HMGB1 signalling pathway components in type 2 diabetic rat retinas and in high glucose cultured ARPE-19 cells. METHODS: Retinal expression of HMGB1 and its receptors in type 2 diabetic rats were detected by western blot and immunohistochemistry. ARPE-19 cells were cultured with low glucose, high glucose (with or without anti-HMGB1 antibody) or mannitol (control) for different lengths of time (12, 24, 48, 72 h). Then expression of HMGB1 and its receptors was measured by immunocytochemistry, ELISA or western blot. Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity and tumour necrosis factor α (TNFα)/vascular endothelial growth factor (VEGF) production in retinas as well as in ARPE-19 cells were detected by ELISA. Furthermore, blood-retinal barrier permeability and ARPE-19 cell viability were measured by Evans-Blue and Cell Counting Kit-8 assay, respectively. RESULTS: HMGB1 signalling pathway components including receptors for HMGB1 as well as NF-κB and TNFα/VEGF were significantly upregulated in type 2 diabetic retinas and in high glucose treated ARPE-19 cells, compared to their respective counterparts. HMGB1 blockage significantly alleviated NF-κB activity and VEGF secretion in ARPE-19 cells cultured with high glucose. In addition, blood-retinal barrier permeability of the diabetic retinas increased, while cell viability of high glucose treated ARPE-19 cells decreased. CONCLUSIONS: Expression of HMGB1 signalling pathway components were increased in diabetic rat retinas and in ARPE-19 cells exposed to high glucose.