Proanthocyanidins attenuate the high glucose-induced damage of retinal pigment epithelial cells by attenuating oxidative stress and inhibiting activation of the NLRP3 inflammasome.

Diabetic retinopathy (DR) is a common diabetic complication known to cause vision impairment and blindness. Previous studies have demonstrated that proanthocyanidins (PACs), polyphenols that are naturally found in several plants and fruits, have powerful antioxidant and anti-inflammatory effects on various cells. However, the effects and underlying mechanism of PACs against DR pathogenesis remain unknown. Here, we investigated the proliferation, apoptosis, and mechanisms of ARPE-19 cells in response to oxidative stress and inflammation under high-glucose conditions with or without PACs treatment. The Cell-Counting Kit-8 assay and western blot analysis showed that treatment with 10 µl PACs significantly increased cell proliferation and the expression level of Bcl-2 in ARPE-19 cells under high-glucose conditions. Moreover, PACs attenuated the high glucose-induced apoptosis, and the increased expression levels of caspase-3 and Bax. Under high-glucose conditions, the generation of reactive oxygen species (ROS) and levels of malondialdehyde increased, whereas the superoxide dismutase content decreased. Moreover, the expression level of the NLRP3 inflammasome, and the release of interleukin 1ß (IL-1ß) and IL-18 increased. PACs reversed all of these high glucose-induced effects on ARPE-19 cells. Additionally, exposure to nigericin sodium salt, an agonist of the NLRP3 inflammasome, upregulated expression of the NLRP3 inflammasome accompanied by the release of IL-1ß and IL-18. Again, treatment with PACs markedly downregulated these effects. Collectively, these results demonstrate that PACs can prevent retinal pigment epithelial cells from high glucose-induced injury via inhibiting the generation of ROS and activation of the NLRP3 inflammasome, suggesting PACs as a potential candidate for the management of DR.

OCT proves that vitreomacular adhesion is significantly more likely to develop vision-threatening retinal complications than vitreomacular separation.

BACKGROUND: SD-OCT is becoming commonplace in everyday practice. Vitreomacular adhesions (VMAs) are being more routinely diagnosed. Predictive studies to the natural course of VMA are thus clinically significant. Spectral domain-optical coherence tomography (SD-OCT) was presently utilized to analyze the incidence of floaters, the complete vitreomacular separation or VMA, the VMA complication, the vitreomacular angle (VMAng), and the complication mechanism. METHODS: Monthly SD-OCT was performed on patients with/without symptomatic floaters. OCT allowed VMA and vitreomacular separation to be compared. The incidence was assessed applying one-tailed Fisher's exact tests. The VMAngs between the inner retina and posterior hyaloid were measured, and the complication mechanism was studied using OCT image. For macular hole (MH), pre- and/or post-operative best corrected visual acuities (BCVAs; LogMAR), refractions and photoreceptor conditions were also evaluated. RESULTS: Totally, 124 eyes were included; there were 116 eyes with VMA and 8 eyes with vitreomacular separation. Considering the percentages over 124 eyes, floaters were present in 14.5% of enrolled eyes (=18/124), consisting of 12.9% of eyes with VMA (16/124) and 1.6% of eyes with vitreomacular separation (2/124). Moreover, there were twelve eyes (9.7%) with VMA-associated vision-threatening complications, including MH (n = 8; 6.5%), retinal detachment (RD; n = 2; 1.6%), vitreomacular traction (VMT; n = 1; 0.8%) and macular pucker (MP; n = 1; 0.8%). Eyes with initial VMA had a significantly greater possibility of complications than eyes with initial vitreomacular separation (p = 0.03). Among these eyes with MH (n = 8), the pre-operative BCVA (LogMAR) was 1.1 ± 0.5, which was insignificantly (p = 0.35) improved to 0.8 ± 0.7 post-operatively. The VMAng of VMA eyes with MHs was 24.2 ± 24.9° (n = 8). The critical VMAng was 13.3°. CONCLUSIONS: A minority of eyes with VMA or vitreomacular separation had floaters. Moreover, the use of SD-OCT could identify vision-threatening sequelae, namely MH, RD, MP and VMT, and this was significantly more frequent in eyes with VMA than in eyes with complete vitreomacular separation. Therefore, SD-OCT might be a useful way of identifying either identity, and evaluating VMA-associated complications. Whether VMA eyes with MH (n = 8) that have a VMAng greater than critical VMAng have a greater likelihood of tangential traction and subsequent MH needs further investigation.

The retinal oxygen metabolism and hemodynamics as a substitute for biochemical tests to predict nonproliferative diabetic retinopathy.

Predicting the occurrence of nonproliferative diabetic retinopathy (NPDR) using biochemical parameters is invasive, which limits large-scale clinical application. Noninvasive retinal oxygen metabolism and hemodynamics of 215 eyes from 73 age-matched healthy subjects, 90 diabetic patients without DR, 40 NPDR, and 12 DR with postpanretinal photocoagulation were measured with a custom-built multimodal retinal imaging device. Diabetic patients underwent biochemical examinations. Two logistic regression models were developed to predict NPDR using retinal and biochemical metrics, respectively. The predictive model 1 using retinal metrics incorporated male gender, insulin treatment condition, diastolic duration, resistance index, and oxygen extraction fraction presented a similar predictive power with model 2 using biochemical metrics incorporated diabetic duration, diastolic blood pressure, and glycated hemoglobin A1c (area under curve: 0.73 vs. 0.70; sensitivity: 76% vs. 68%; specificity: 64% vs. 62%). These results suggest that retinal oxygen metabolic and hemodynamic biomarkers may replace biochemical parameters to predict the occurrence of NPDR .

Changes in foveal avascular zone area and retinal vein diameter in patients with retinal vein occlusion detected by fundus fluorescein angiography.

Purpose: To investigate changes in foveal avascular area (FAZ) and retinal vein diameter in patients with retinal vein occlusion (RVO) after intravitreal ranibizumab, and to analyze the correlation between ranibizumab therapy and visual gain. Methods: This retrospective study enrolled 95 eyes of 95 patients who had accepted three consecutive monthly ranibizumab injections, including 50 branch RVOs (BRVOs) and 45 central RVOs (CRVOs). BRVOs were divided into ischemia group (n = 32) and non-ischemia group (n = 18), and CRVOs also had ischemia group (n = 28) and non-ischemia group (n = 17). Comprehensive ophthalmic examinations were performed before the first injection and after 6, 12, and 24 months. The FAZ was manually circumscribed on early-phase images of fundus fluorescein angiography. Retinal vein diameters were measured on fundus photographs. Results: After three injections, the FAZ area was significantly enlarged firstly and then reduced in all ischemic RVOs and the non-ischemic BRVOs (p < 0.05), while the retinal vein diameter was significantly reduced firstly and then increased in all groups except for unobstructed branch veins of non-ischemic BRVOs (p < 0.05). The correlation between the FAZ area and best corrected visual acuity was statistically significant in all CRVOs (non-ischemic, r = 0.372; ischemic, r = 0.286; p < 0.01) and ischemic BRVOs (r = 0.180, p < 0.05). Spearman's correlation analysis revealed that the retinal vein diameter was significantly correlated to the larger FAZ area in obstructed branch veins of ischemic BRVOs (r = -0.31, p < 0.01), inferior temporal branch veins of non-ischemic CRVOs (r = -0.461, p < 0.01) and ischemia CRVO groups (superior temporal branch vein, r = -0.226, p < 0.05; inferior temporal branch vein, r = -0.259, p < 0.01). Conclusion: After three consecutive monthly ranibizumab injections, the FAZ area was enlarged and retinal vein diameter reduced with gradual recovery to near baseline from 12 months. These results suggest that ranibizumab therapy can worsen macular ischemia and prevent visual gain in the short term. It has important significance for the treatment and prognosis of RVO, although the natural course of RVO may also affect ischemia and visual gain.

Inhibitory effect on subretinal fibrosis by anti-placental growth factor treatment in a laser-induced choroidal neovascularization model in mice.

AIM: To investigate whether anti-placental growth factor (PGF) can inhibit subretinal fibrosis and whether this effect is mediated by the inhibitory effect of PGF on epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. METHODS: Subretinal fibrosis model was established in laser induced choroidal neovascularization (CNV) mice on day 21 after laser photocoagulation. Immunofluorescence staining (IFS) of cryosections and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of PGF. IFS of whole choroidal flat-mounts was used to detect the degree of subretinal fibrosis. IFS of cryosections and ELISA were used to detect the expression of EMT related indicators in subretinal fibrosis lesions. RESULTS: The expression of PGF protein in subretinal fibrosis lesions was significantly up-regulated (P<0.05), and mainly co-stained with pan-cytokeratin labeled RPE cells. Intravitreal injection of anti-PGF neutralizing antibody reduced the area of subretinal fibrosis and the ratio of fibrotic/angiogenic area significantly at the concentrations of 0.25, 0.5, 1.0, and 2.0 µg/µL (all P<0.05). The expression of E-cadherin in the local RPE cells decreased, while α-SMA increased significantly in subretinal fibrosis lesions, and the application of anti-PGF neutralizing antibody could reverse these changes (P<0.05). CONCLUSION: The expression of PGF is up-regulated in the lesion site of subretinal fibrosis and mainly expressed in RPE cells. Intravitreal injection of anti-PGF neutralizing antibody can significantly inhibit the degree of subretinal fibrosis in CNV mice, and this effect may be mediated by the inhibition of PGF on EMT of RPE cells.

A Magnified Adaptive Feature Pyramid Network for automatic microaneurysms detection.

Diabetic retinopathy (DR), as an important complication of diabetes, is the primary cause of blindness in adults. Automatic DR detection poses a challenge which is crucial for early DR screening. Currently, the vast majority of DR is diagnosed through fundus images, where the microaneurysm (MA) has been widely used as the most distinguishable marker. Research works on automatic DR detection have traditionally utilized manually designed operators, while a few recent researchers have explored deep learning techniques for this topic. But due to issues such as the extremely small size of microaneurysms, low resolution of fundus pictures, and insufficient imaging depth, the DR detection problem is quite challenging and remains unsolved. To address these issues, this research proposes a new deep learning model (Magnified Adaptive Feature Pyramid Network, MAFP-Net) for DR detection, which conducts super-resolution on low quality fundus images and integrates an improved feature pyramid structure while utilizing a standard two-stage detection network as the backbone. Our proposed detection model needs no pre-segmented patches to train the CNN network. When tested on the E-ophtha-MA dataset, the sensitivity value of our method reached as high as 83.5% at false positives per image (FPI) of 8 and the F1 value achieved 0.676, exceeding all those of the state-of-the-art algorithms as well as the human performance of experienced physicians. Similar results were achieved on another public dataset of IDRiD.

Efficacy and safety of 0.0015% tafluprost versus 0.005% latanoprost in primary open angle glaucoma, ocular hypertension: a Meta-analysis.

AIM: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of tafluprost 0.0015% eye drops [benzalkonium chloride (BAK) 0.1 mg/mL] compared with that of latanoprost 0.005% eye drops (BAK 0.2 mg/mL) for primary open angle glaucoma (POAG) and ocular hypertension (OHT). METHODS: All the randomized controlled trials (RCTs) about treating POAG and OHT comparing tafluprost and latanoprost were collected by searching PubMed, Embase, Cochrane Library, CNKI and VIP. The outcomes of interest to evaluate the clinical efficacy and adverse effects included IOP and patient-related drop discomfort. RESULTS: Five RCTs involving 888 glaucoma patients were included. The results showed that, 1) at the end of the study, no statistically significant differences were observed in IOP reduction [standard mean difference (SMD) =0.48, 95%CI 0.07 to 0.88, P=0.085] between tafluprost and latanoprost; 2) No statistically significant differences were observed in adverse events of foreign-body sensation [relative risk (RR) =0.62, 95%CI 0.26 to 1.46, P=0.269], eye irritation (RR=1.16, 95%CI 0.49 to 2.75, P=0.744), eye pain (RR=2.000, 95%CI 0.949 to 4.216, P=0.07), iris hyper-pigmentation (RR=0.741, 95%CI 0.235 to 2.334, P=0.61), dry eye (RR=1.154, 95%CI 0.409 to 3.256, P=0.79) and eye pruritus (RR=1.600, 95%CI 0.536 to 4.774, P=0.4) between tafluprost and latanoprost. However, tafluprost showed more reported incidence of conjunctival hyperaemia than latanoprost (RR=2.11, 95%CI 1.24 to 3.59, P=0.006). CONCLUSION: Tafluprost 0.0015% eye drops (BAK 0.1 mg/mL) and latanoprost 0.005% eye drops (BAK 0.2 mg/mL) are comparable in lowering IOP for open angle glaucoma (OAG) and OHT. It does not differ in the incidence of foreign-body sensation, eye irritation, eye pain, iris hyper-pigmentation, dry eye and eye pruritus, but tafluprost shows less ocular tolerability because of more incidence of conjunctival hyperaemia.

Comparison of Outcomes after Phacoemulsification with Two Different Corneal Incision Distances Anterior to the Limbus.

PURPOSE: To compare visual performance and visual quality outcomes after phacoemulsification with two different clear corneal incision (CCI) distances anterior to the limbus in senile cataract patients. METHODS: Retrospective case series. Patients who had undergone phacoemulsification were divided into two groups according to the CCI distances anterior to the limbus. The CCI distances in group A range from 1 mm to 1.5 mm, while those in group B range from 0.5 mm to 1 mm. The visual acuity, refraction, surgically induced astigmatism (SIA), corneal aberrations, anterior segment parameters, and subjective vision quality were evaluated. RESULTS: This study enrolled 54 eyes, with 27 eyes per group. Both groups had significant improvement in postoperative uncorrected visual acuity (UCVA) and corrected distance visual acuity (CDVA) (P < 0.05). There were no statistically significant between-group differences in postoperative UDVA, CDVA, SIA, corneal aberrations, anterior segment parameters, or VF-QOL questionnaire performance (P > 0.05). CONCLUSIONS: The phacoemulsification with CCI distances ranging from 0.5 mm to 1.5 mm is an effective and safe therapy to senile cataract. The CCI distance anterior to the limbus that ranges from 0.5 mm to 1.5 mm is recommended for routine phacoemulsification.

Association of urinary albumin excretion with central foveal thickness and intravitreal conbercept treatment frequency in patients with diabetic macular edema.

AIM: To investigate the effect of albuminuria on diabetic macular edema (DME) and the possible association between baseline urinary albumin excretion (UAE) and intravitreal conbercept (IVC) treatment frequency in DME patients. METHODS: In this hospital-based retrospective study, a total of 350 in-patients with type 2 diabetes mellitus were recruited and their clinical records were reviewed. Thereafter, 52 patients identified with severe non-proliferative diabetic retinopathy (NPDR) combined with albuminuria were divided into the microalbuminuria (UAE 30-300 mg/24h) and macroalbuminuria (UAE>300 mg/24h) groups, which were compared and analyzed by both independent sample t-test and Chi-square test. Correlations between the systemic variables and the central foveal thickness (CFT) were evaluated using Spearman's correlation and linear regression analyses. Of the 52 patients with center-involved DME, 43 received an initial combined injection of conbercept (0.5 mg/0.05 mL) and triamcinolone acetonide (1 mg/0.05 mL), followed by an IVC injection, as needed. The relationship between baseline UAE and number of IVC injections during the first year of treatment was analyzed using Spearman's partial correlation. RESULTS: Of 350 patients, a higher incidence of DME was observed in severe non-proliferative retinopathy (NPDR) patients than that observed in other groups. By dividing the 52 patients with severe NPDR into the micro- and macro-albuminuria subgroups, significant differences in CFT, systolic blood pressure, total cholesterol and serum creatinine levels, and UAE were revealed. Furthermore, a positive liner correlation between the UAE and CFT was found. Finally, the partial correlation coefficient adjusted for either the CFT or UAE indicated that both parameters directly correlated with the number of IVC injections administered during the 12mo of follow-up. CONCLUSION: Generally, macular edema occurred in patients with severe NPDR, for whom the UAE is an independent risk predictor of DME. The baseline UAE and CFT predicted the treatment frequency of IVC injections administered in the first year for eyes with DME.

[Effect of different clear corneal incision sites on surgery efficacy and anterior segment parameters in patients undergoing phacoemulsification].

OBJECTIVE: To determine the safe distance range of clear corneal incision (CCI) from the corneal limbus and how different CCI sites affect surgery efficacy and anterior segment parameters in patients undergoing phacoemulsification. METHODS: This retrospective case-control study was conducted in 44 patients (44 eyes) undergoing phacoemulsification and IOL implantation. The patients were divided into two groups with CCI distances ranging from 1 mm to 1.5 mm (group A, n= 22) and from 0.5 mm to 1.0 mm (group B, n= 22). The visual acuity, surgically induced astigmatism (SIA), corneal aberration, and anterior segment parameters were analyzed. RESULTS: Compared with the preoperative data, all the patients showed significant improvements in the postoperative uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), anterior chamber depth (ACD), and anterior chamber angle (ACA) after the surgery (P < 0.05). No significant differences were found between the two groups in postoperative UCVA, BCVA, SIA, total corneal aberration RMS, lower- and higher-order aberration RMS, spherical aberration (Z40), horizontal three leaf clover (Z33), vertical three leaf clover(Z3-3), horizontal coma(Z31), vertical coma(Z3-1), ACD, ACA, anterior chamber volume, or central corneal thickness (P>0.05). CONCLUSIONS: Phacoemulsification is an effective therapy for cataract with a CCI distance range either of 1-1.5 mm or 0.5-1.0 mm. These two CCI distance ranges produce no significant differences in the visual quality following phacoemulsification, indicating that a CCI distance range of 0.5-1.5 mm can be safe for phacoemulsification.

Effects of lentiviral RNA interference-mediated downregulation of integrin-linked kinase on biological behaviors of human lens epithelial cells.

AIM: To investigate the effects of lentivirus (LV) mediated integrin-linked kinase (ILK) RNA interference (RNAi) on biological behaviors of human lens epithelial cells (LECs). METHODS: Human cataract LECs and immortalized human LEC line, human lens epithelial (HLE) B-3 cells were transfected by lentiviral vector expressing ILK-specific short hairpin RNA (shRNA) and then stimulated by transforming growth factor-ß (TGF-ß), the silencing of ILK gene and protein was identified by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot methods; biological behaviors including cell cycle and apoptosis, cell morphology, α-smooth muscle actin (SMA) stress fiber formation and cell migration were examined. RESULTS: Remarkable decreases of ILK protein expression were detected in LECs carrying lentiviral ILK-shRNA vector; flow cytometry revealed arresting of cell cycle progression through the G1/S transition and higher apoptosis rate in ILK-RNAi-LV transfected cells. Less α-SMA stress fiber formation and migration was observed in ILK-RNAi-LV transfected LECs. CONCLUSION: The present study demonstrated that ILK was an important regulator for LECs proliferation and migration. LV mediated ILK RNAi is an effective way to decrease ILK-regulated cell growth by arresting cell cycle progression and increasing cell apoptosis, as well as, to prevent cell migration by inhibiting TGF-ß induced α-SMA stress fiber formation. Thus, LV mediated ILK RNAi might be useful to prevent posterior capsular opacification.