Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

INTRODUCTION: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. RESULTS: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. CONCLUSIONS: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Comparison of binocular visual quality in six treatment protocols for bilateral cataract surgery with presbyopia correction: a prospective two-center single-blinded cohort study.

OBJECTIVE: To compare the postoperative binocular visual quality in six treatment protocols for bilateral age-related cataract surgery with presbyopia correction for clinical decisions. MATERIALS AND METHODS: In this prospective two-center single-blinded cohort study, participants from North or South China who underwent bilateral phacoemulsification and intraocular lens implantation were divided into six protocols: monovision, diffractive bifocal, mixed, refractive bifocal, trifocal, and micro-monovision extended range of vision (EROV). Binocular visual quality was evaluated at 3 months postoperatively, including binocular uncorrected full-range visual acuity, binocular defocus curves (depth of focus [DoF] and area under the curve [AUC]), binocular visual function (fusion function and stereopsis), binocular subjective spectacle independence rates, visual analog scale (VAS) of overall satisfaction, 25-item visual function questionnaire (VFQ-25), and binocular dysphotopsia symptoms. RESULTS: Of the 300 enrolled patients, 272 (90.7%; 544 eyes) were analyzed. The trifocal protocol showed excellent binocular full-range visual acuity and the best performance for most DoFs and AUCs. The monovision protocol presented the worst binocular visual quality in most perspectives, especially in convergence, distance, and near stereopsis (p < 0.001). The full-range subjective spectacle independence rates were sorted from highest to lowest as follows: trifocal (84.8%), refractive bifocal (80.9%), EROV (80.0%), mixed (73.3%), diffractive bifocal (65.2%), and monovision (32.6%) protocols, with no statistically significant differences between the former five protocols (p > 0.05). The EROV protocol achieved the highest VAS and VFQ-25 scores. The incidence of postoperative binocular dysphotopsia symptoms was comparable in all protocols. CONCLUSIONS: The trifocal protocol showed the best performance, and the monovision protocol presented the worst performance in most perspectives of binocular visual quality for presbyopia correction. The refractive bifocal, mixed, or EROV protocols can provide an approximate performance as a trifocal protocol. Ophthalmologists can customize therapies using different protocols.

Influence of decentration of plate-haptic toric intraocular lens on postoperative visual quality.

BACKGROUND: To evaluate the influence of decentration of plate-haptic toric intraocular lens (IOLs) on visual quality. METHODS: This study enrolled 78 eyes of 78 patients. Patients in group A were implanted with toric IOLs, and patients in group B were implanted with monofocal IOLs. All patients were divided into group A1 and B1 (decentration below 0.3 mm) and group A2 and B2 (decentration above 0.3 mm). The uncorrected distance visual acuity (UDVA), best corrected visual acuity (BCVA), modulation transfer function cutoff (MTF cutoff), objective scatter index (OSI), strehl ratio (SR), optical interference and patients' satisfaction were measured in different pupils at three months postoperatively. The associations between decentration and visual quality were analyzed by Spearman correlation. RESULTS: There were no significant differences in UDVA, BCVA, MTF cutoff, OSI, SR, optical interference and patients' satisfaction among subgroups. The differences in decentration between groups A and B were not statistically significant. In group A2, the total higher order aberrations (tHOAs) at pupil sizes of 3 mm (P = 0.046), 5 mm (P = 0.014), spherical aberrations at pupil sizes of 3 mm (P = 0.011), 4 mm (P = 0.014), 5 mm (P = 0.000), secondary astigmatism at pupil sizes of 3 mm (P = 0.002), 4 mm (P = 0.005) were higher than in group B2. Compared to group A1, group A2 had higher spherical aberrations at pupil sizes of 4 mm (P = 0.042), 5 mm (P = 0.001), 6 mm (P = 0.038), secondary astigmatism at pupil sizes of 3 mm (P = 0.013), 4 mm (P = 0.005), 6 mm (P = 0.013). Group B2 has higher coma and secondary astigmatism than group B1 at 6-mm pupil (P = 0.014, P = 0.045). Significant positive correlations were found between spherical aberrations and the decentration of group A1 and A2 at 6-mm pupils. CONCLUSION: The decentration above 0.3 mm negatively affected visual quality due to increased tHOAs, spherical aberrations, coma and secondary astigmatism aberrations, the influence become larger with increasing pupil diameter. And toric IOLs are more affected by decentration than monofocal IOLs.

3% diquafosol sodium eye drops in Chinese patients with dry eye: a phase IV study.

Introduction: The efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear. Methods: 3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer's tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment. Results: Based on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs. Discussion: The use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

Cost-Effectiveness of Presbyopia Correction Among Seven Strategies of Bilateral Cataract Surgery Based on a Prospective Single-Blind Two-Center Trial in China.

INTRODUCTION: The aim of this study was to explore a method to rank the cost-effectiveness of presbyopia correction in diverse strategies of bilateral cataract surgery to provide references for healthcare policymakers in rationalizing resource utilization and surgeons in customizing patient management. METHODS: The cost-effectiveness analysis based on a prospective single-blind two-center clinical trial included seven strategies in bilateral cataract surgery: monofocal, monovision, diffractive bifocal, blended, refractive bifocal, trifocal, and extended depth of focus (EDOF) strategies. The effectiveness according to the objective spectacle independence rate (hereafter "rate", a novel indicator defined as the proportion of patients with binocular uncorrected distance, intermediate and near visual acuity all better than 0.1 logMAR, logarithm of the minimum angle of resolution), costs, average cost-effectiveness ratios (ACERs, $/1% rate), and incremental cost-effectiveness ratios (ICERs, $/1% incremental rate) were estimated. RESULTS: In 194 participants (388 eyes), the trifocal strategy achieved the highest rate [93.10% (95% confidence interval (CI) 83.8-102.35%)]. The refractive bifocal strategy had the minimum ACER [$45.54/1% rate (95% CI 34.57-56.50)], followed by the blended [$59.10/1% rate (95% CI 31.72-86.48)], diffractive bifocal [$69.06/1% rate (95% CI 30.89-107.21)], EDOF [$72.85/1% rate (95% CI 52.02-93.70)], trifocal [$93.01/1% rate (95% CI 83.23-102.79)], monovision [$136.83/1% rate (95% CI - 55.40 to 329.14)], and monofocal [$264.45/1% rate (95% CI - 97.45 to 626.55)] strategies. Compared with the refractive bifocal strategy, the probabilities that the trifocal strategy (ICER $289.74/1% incremental rate) is very cost-effective and cost-effective were 81.7% and 93.2%, respectively, at the wiliness-to-pay threshold of one and three times China's annual disposable income per capita in 2021 per 10% incremental rates. CONCLUSIONS: Cost-effectiveness analysis with ACER and ICER according to objective spectacle independence rate is a helpful tool to identify highly cost-effective presbyopia-correcting strategies in cataract surgery for clinical and policy decisions. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04265846).

Cavin-1 promotes M2 macrophages/microglia polarization via SOCS3.

PURPOSE: Our study aimed to investigate the function of Cavin-1 and SOCS3 in macrophages/microglia M2 polarization and further explored the relevant mechanism. METHODS: Expression levels of Cavin-1 and SOCS3 in macrophages/microglia were measured by western blotting and RT-PCR, respectively. Then, Cavin-1 or SOCS3 was gene silenced by a siRNA approach, and gene silencing efficiency was determined by western blotting. Next, co-immunoprecipitation (Co-IP) was employed to further analyze the interaction between Cavin-1 and SOCS3. Finally, the activation of STAT6/PPAR-γ signaling was evaluated using western blotting, and the M2 macrophages/microglia polarization was validated by measuring the mRNA expression of M2 markers by RT-PCR. RESULTS: In the polarization process of macrophages/microglia to M2 phenotype, both Cavin-1 and SOCS3 increased synchronously at protein and mRNA level, reached the peak at the 6 h, and then decreased. After Cavin-1 or SOCS3 silencing, the expression of Cavin-1 and SOCS3 declined. These results suggested that Cavin-1 and SOCS3 were positively correlated in macrophages/microglia, and this conjecture was verified by Co-IP. Besides, Cavin-1 silencing not only suppressed the activation of STAT6/PPAR-γ pathway, but also suppressed the release of anti-inflammatory factors. Finally, we found that SOCS3 overexpression reversed the inhibitory effect of Cavin-1 silencing on the release of anti-inflammatory factors in M2 macrophages/microglia. CONCLUSIONS: Cavin-1 and SOCS3 are actively involved in the process of M2 macrophages/microglia polarization. As a SOCS3 interacting protein, Cavin-1 can promote M2 macrophages/microglia polarization via SOCS3.

The Clinical Value of Explainable Deep Learning for Diagnosing Fungal Keratitis Using in vivo Confocal Microscopy Images.

Background: Artificial intelligence (AI) has great potential to detect fungal keratitis using in vivo confocal microscopy images, but its clinical value remains unclarified. A major limitation of its clinical utility is the lack of explainability and interpretability. Methods: An explainable AI (XAI) system based on Gradient-weighted Class Activation Mapping (Grad-CAM) and Guided Grad-CAM was established. In this randomized controlled trial, nine ophthalmologists (three expert ophthalmologists, three competent ophthalmologists, and three novice ophthalmologists) read images in each of the conditions: unassisted, AI-assisted, or XAI-assisted. In unassisted condition, only the original IVCM images were shown to the readers. AI assistance comprised a histogram of model prediction probability. For XAI assistance, explanatory maps were additionally shown. The accuracy, sensitivity, and specificity were calculated against an adjudicated reference standard. Moreover, the time spent was measured. Results: Both forms of algorithmic assistance increased the accuracy and sensitivity of competent and novice ophthalmologists significantly without reducing specificity. The improvement was more pronounced in XAI-assisted condition than that in AI-assisted condition. Time spent with XAI assistance was not significantly different from that without assistance. Conclusion: AI has shown great promise in improving the accuracy of ophthalmologists. The inexperienced readers are more likely to benefit from the XAI system. With better interpretability and explainability, XAI-assistance can boost ophthalmologist performance beyond what is achievable by the reader alone or with black-box AI assistance.

A deep transfer learning framework for the automated assessment of corneal inflammation on in vivo confocal microscopy images.

PURPOSE: Infiltration of activated dendritic cells and inflammatory cells in cornea represents an important marker for defining corneal inflammation. Deep transfer learning has presented a promising potential and is gaining more importance in computer assisted diagnosis. This study aimed to develop deep transfer learning models for automatic detection of activated dendritic cells and inflammatory cells using in vivo confocal microscopy images. METHODS: A total of 3453 images was used to train the models. External validation was performed on an independent test set of 558 images. A ground-truth label was assigned to each image by a panel of cornea specialists. We constructed a deep transfer learning network that consisted of a pre-trained network and an adaptation layer. In this work, five pre-trained networks were considered, namely VGG-16, ResNet-101, Inception V3, Xception, and Inception-ResNet V2. The performance of each transfer network was evaluated by calculating the area under the curve (AUC) of receiver operating characteristic, accuracy, sensitivity, specificity, and G mean. RESULTS: The best performance was achieved by Inception-ResNet V2 transfer model. In the validation set, the best transfer system achieved an AUC of 0.9646 (P<0.001) in identifying activated dendritic cells (accuracy, 0.9319; sensitivity, 0.8171; specificity, 0.9517; and G mean, 0.8872), and 0.9901 (P<0.001) in identifying inflammatory cells (accuracy, 0.9767; sensitivity, 0.9174; specificity, 0.9931; and G mean, 0.9545). CONCLUSIONS: The deep transfer learning models provide a completely automated analysis of corneal inflammatory cellular components with high accuracy. The implementation of such models would greatly benefit the management of corneal diseases and reduce workloads for ophthalmologists.

Impact of air injection on subretinal fluid following successful scleral buckling surgery for macular-involving retinal detachment.

Air injection is an accessory technique during scleral buckling (SB). Subclinical subretinal fluid (SRF) may presence and persistent after SB. The impact of air injection on SRF is unclear. In the study, we retrospectively enrolled 51 patients with macular-involving RD who had undergone successful SB. They were categorized into Group A (SB without air injection) and Group B (SB with air injection). First, we found that although group B seem to be severer than group A before surgery, Kaplan-Meier graph showed that SRF absorbed more rapidly in group B after surgery, and the incidence of SRF in group B was much lower during the whole follow-up period. Moreover, the cases with superior breaks had the lowest incidence. Second, during the follow-up period, there was no significant difference about postoperative complication between two groups. Lastly, risk factors for persistent SRF were investigated with binary logistic regression, and no risk factor was found. In conclusion, air injection during the SB might accelerate SRF absorption and reduce the incidence of persistent SRF, especially for the longstanding macular-off RD with superior breaks.

Epigenetic Landscape Analysis of the Long Non-Coding RNA and Messenger RNA in a Mouse Model of Corneal Alkali Burns.

Purpose: Corneal alkali burns (CABs) are a common clinical ocular disease, presenting a poor prognosis. Although some long noncoding RNAs (lncRNAs) reportedly play a key role in epigenetic regulation associated with CABs, studies regarding the lncRNA signature in CABs remain rare and elusive. Methods: A CAB model was established in C57BL/6J mice and profiling of lncRNA expressions was performed by RNA-Seq. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to predicate the related pathological pathways and candidate genes. RT-qPCR was used to verify the expression pattern of lncRNAs and related mRNAs, both in vitro and in vivo. Data were statistically analyzed by GraphPad Prism version 6.0. Results: In all, 4436 aberrantly expressed lncRNAs were identified in CAB mice when compared with control mice. In the top 13 aberrantly expressed lncRNAs, Bc037156 and 4930511E03Rik were confirmed as the most significantly altered lncRNAs. Pathway analysis revealed that mitogen-activated protein kinase (MAPK) signaling pathway was most enriched. Following 4930511E03Rik siRNA treated, Srgn, IL-1ß and Cxcr2 were significant upregulated in corneal epithelial cells, corneal keratocytes, and bone marrow dendritic cells, with NaOH treatment. Moreover, after Bc037156 siRNA treated, expression levels of IL-1ß and Srgn were significantly downregulated in the three cell lines. Conclusions: Our study suggests that Bc037156 and 4930511E03Rik may be involved in inflammation, immune response, and neovascularization by regulating Srgn, IL-1ß, and Cxcr2 expression after CAB. These candidate lncRNAs and mRNAs may be the potential targets for the treatment strategy of the alkali injured cornea.

Association of High-Mobility Group Box-1 with Inflammationrelated Cytokines in the Aqueous Humor with Acute Primary Angle-Closure Eyes.

AIM: The aim of this study was to measure the levels of High-mobility group box-1 (HMGB1) and inflammation-related cytokines in the aqueous humor of patients with acute primary angle-closure glaucoma (APAG) and age-related cataract eyes (ARC). METHODS: Aqueous humor samples were obtained from 59 eyes of 59 Chinese subjects (APAG, 32 eyes; and ARC, 27eyes). The multiplex bead immunoassay technique was used to measure the levels of HMGB1 and IL-8, IL-6, G-CSF, MCP-3, VEGF, sVEGFR- 1, sVEFGR-2, TNF-α, PDGF, and IL-10 in aqueous. The data of Patients' demographics and preoperative intraocular pressure (IOP) were also collected for detailed analysis. RESULTS: The APAG group showed significantly elevated concentrations of HMGB1, IL- 8, IL-6, G-CSF, VEGF, sVEGFR-1, and TNF-α than those in the ARC group. Aqueous HMGB1 level correlated significantly with IOP, IL-8, IL-6, G-CSF and sVEGFR-1 levels but not with age, TNF-α, or VEGF levels. CONCLUSION: The aqueous level of HMGB1 is elevated in APAG and associated with aqueous level of inflammation-related cytokines, suggesting an association between elevated levels of HMGB1, APAC and certain inflammatory modulators which, of course, should lead to further investigations in order to demonstrate the cause and effect.

Fasudil attenuates glial cell-mediated neuroinflammation via ERK1/2 and AKT signaling pathways after optic nerve crush.

To investigate the functional role of fasudil in optic nerve crush (ONC), and further explore its possible molecular mechanism. After ONC injury, the rats were injected intraperitoneally either with fasudil or normal saline once a day until euthanized. RGCs survival was assessed by retrograde labeling with FluoroGold. Retinal glial cells activation and population changes (GFAP, iba-1) were measured by immunofluorescence. The expressions of cleaved caspase 3 and 9, p-ERK1/2 and p-AKT were detected by western blot. The levels of the pro-inflammatory cytokines were determined using real-time polymerase chain reaction. Fasudil treatment inhibited RGCs apoptosis and reduced RGCs loss demonstrated by the decreased apoptosis-associated proteins expression and the increased fluorogold labeling of RGCs after ONC, respectively. In addition, the ONC + fasudil group compared had a significantly lower expression of GFAP and iba1 compared with the ONC group. The levels of pro-inflammatory cytokines were significantly reduced in the ONC + fasudil group than in the ONC group. Furthermore, the phosphorylation levels of ERK1/2 and AKT (p-ERK1/2 and p-AKT) were obviously elevated by the fasudil treatment. Our study demonstrated that fasudil attenuated glial cell-mediated neuroinflammation by up-regulating the ERK1/2 and AKT signaling pathways in rats ONC models. We conclude that fasudil may be a novel treatment for traumatic optic neuropathy.

Deep learning-based automated diagnosis of fungal keratitis with in vivo confocal microscopy images.

BACKGROUND: The aim of this study was to develop an intelligent system based on a deep learning algorithm for automatically diagnosing fungal keratitis (FK) in in vivo confocal microscopy (IVCM) images. METHODS: A total of 2,088 IVCM images were included in the training dataset. The positive group consisted of 688 images with fungal hyphae, and the negative group included 1,400 images without fungal hyphae. A total of 535 images in the testing dataset were not included in the training dataset. Deep Residual Learning for Image Recognition (ResNet) was used to build the intelligent system for diagnosing FK automatically. The system was verified by external validation in the testing dataset using the area under the receiver operating characteristic curve (AUC), accuracy, specificity and sensitivity. RESULTS: In the testing dataset, 515 images were diagnosed correctly and 20 were misdiagnosed (including 6 with fungal hyphae and 14 without). The system achieved an AUC of 0.9875 with an accuracy of 0.9626 in detecting fungal hyphae. The sensitivity of the system was 0.9186, with a specificity of 0.9834. When 349 diabetic patients were included in the training dataset, 501 images were diagnosed correctly and thirty-four were misdiagnosed (including 4 with fungal hyphae and 30 without). The AUC of the system was 0.9769. The accuracy, specificity and sensitivity were 0.9364, 0.9889 and 0.8256, respectively. CONCLUSIONS: The intelligent system based on a deep learning algorithm exhibited satisfactory diagnostic performance and effectively classified FK in various IVCM images. The context of this deep learning automated diagnostic system can be extended to other types of keratitis.

The expression and role of PIDD in retina after optic nerve crush.

To examine the expression of P53-induced protein with a death domain (PIDD) at retina in animal model of optic nerve crush (ONC) and to investigate the role of PIDD in retinal glial activation and NF-κB activation induced by optic nerve damage, ONC animal model was established in Sprague-Dawley rats. PIDD has three isoforms (Isof); Western blot was performed to examine the expression of PIDD (Isof-1, Isof-2, and Isof-3, respectively) in retina at different time points after ONC. Retinal glial activation is closely associated with retinal neuronal death and is monitored by the expression of GFAP+ glial cells and IBA1+ microglia, then activated microglia leads to inflammatory cytokine production. NF-kB activation in glial cells also can promote neuronal death. In our study, the role of PIDD in retinal glial activation and NF-kB activation was investigated with PIDD inhibition selectively. PIDD expression (Isof-1 and Isof-3) was dramatically increased, and peaked at 3 days after ONC, while Isof-2 did not show any difference. In the ONC animal model, the number of GFAP+ glial cells and IBA1+ microglia in retinal layers was increased significantly, inflammatory cytokine production was upregulated, and NF-κB in glial cell was also activated. Moreover, those responses induced by optic nerve damage were attenuated with PIDD inhibition, which indicated that PIDD could regulate retinal glial activation, neuro-inflammation, and NF-κB activation. These results provided the direct demonstration that the PIDD (Isof-1and Isof-3) was overexpressed in retina after ONC, and PIDD may be involved in retinal neurodegenerative diseases by regulating retinal glial activation and NF-κB activation.

Comparison of Femtosecond Laser-Assisted Cataract Surgery and Conventional Phacoemulsification in Shallow Anterior Chambers and Glaucoma.

PURPOSE: To compare femtosecond laser-assisted cataract surgery (FLACS) versus conventional phacoemulsification in shallow anterior chamber cataract patients with glaucoma or zonulysis. METHODS: This was a single-center retrospective review of cataract surgeries in shallow anterior chamber and glaucoma patients between January 2016 and December 2018 in which a LenSx femtosecond laser was used. The outcome measures included pre- and postoperative uncorrected and corrected distance visual acuity (UDVA and CDVA), intraocular pressure (IOP), endothelial cell density (ECD), endothelial cell loss (ECL), and object scatter index (OSI). RESULTS: One hundred and six eyes of 106 patients with a mean anterior chamber depth of 1.54 ± 0.51 mm were included in this study. Among them, 26 (23.2%) had zonulysis and 18 eyes had capsular tension ring implantation in general. The percentage of capsular tension ring implantation was statistically significantly lower in the FLACS group (P = 0.027). The UDVA, CDVA, ECD, and IOP were not statistically significant between the two groups at all time points. The postoperative ECL and OSI of the FLACS group was better than those of the conventional group (P < 0.01). CONCLUSIONS: FLACS can reduce ECL and improve visual quality compared to the conventional phacoemulsification in shallow anterior chamber patients. Also, it has the trend of reducing the use of capsular tension rings in subluxated cataracts. It is an ideal choice for patients with complicated cataract such as with shallow anterior chambers, glaucoma, and zonulysis.

Involvement of Upregulated P53-Induced Death Domain Protein in Retinal Ganglion Cells Apoptosis After Optic Nerve Crush.

PURPOSE: Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determine the physiological relevance of PIDD in RGCs apoptosis in an optic nerve crush (ONC) model. METHODS: All animals were evenly randomized into four groups: sham-control group, con-siRNA group, ONC group, and PIDD-siRNA group (ONC +PIDD-siRNA). Expressions of PIDD, caspase-2, Brn3a and tBid in ONC model were analyzed by Western blot and immunofluorescence. Mean densities of RGCs/mm2 were calculated with Fluoro-Gold (FG). Moreover, we tested the effect of PIDD-siRNA on ONC-induced RGCs apoptosis using TUNEL staining. RESULTS: The level of full-length PIDD was weakly present and showed no significant differences at any time points. PIDD-CC and PIDD-C were significantly up-regulated in the retina at 3 days after ONC. Meanwhile, the expression of PIDD was significantly increased in Brn3a (a marker of RGCs) positive cells, indicating that the localization of PIDD appeared to be confined to RGCs. Furthermore, inhibition of PIDD prevented RGCs apoptosis by inhibiting caspase-2 and tBid activation. CONCLUSION: Taken together, PIDD may play a crucial role in RGCs apoptosis after ONC, and this process may be relevant to caspase-2 and tBid.

Comparison of subfoveal choroidal thickness in eyes with CRVO and BRVO.

BACKGROUND: To evaluate the subfoveal choroidal thickness (SFCT) in eyes with macular edema (ME) secondary to retinal vein occlusion(RVO), and to investigate the short term response after a single intravitreal ranibizumab (IVR) injection. What is more, to compare SFCT and SFCT change between central RVO (CRVO) and branch RVO (BRVO). METHODS: In the retrospective study, we had collected 36-six treatment-naïve patients with unilateral ME secondary to RVO (including 19 CRVO and 17 BRVO). All patients had received IVR injection after newly diagnosed. The SFCT was measured at the onset and after 2 weeks of IVR injection. Paired t test was performed to compare the SFCT of RVO eyes and fellow eyes, as well as the SFCT of pre-injection and post-injection. In further, independent t test was used to compare SFCT and SFCT change between CRVO eyes and BRVO eyes. RESULTS: The mean SFCT at the onset was 326.03 ± 30.86 µm in CRVO eyes, which was significantly thicker than that in contralateral fellow eyes (p < 0.01, paired t test), and reduced to 294.15 ± 30.83 µm rapidly after 2 weeks of IVR injection (p < 0.01, paired t test). Similarly, the SFCT in BRVO eyes was significantly thicker than that in contralateral eyes at the onset, and decreased significantly after IVR injection. However, our findings showed that there was no statistically significant difference in SFCT and SFCT reduction after IVR injection between CRVO eyes and BRVO eyes. CONCLUSIONS: The SFCT in eyes with ME secondary to CRVO and BRVO was significantly thicker than that in fellow eyes, and decreased significantly within a short time in response to a single IVR injection. In further, the study showed that SFCT and SFCT change had no correlation with RVO subtypes.

CD200Fc Attenuates Retinal Glial Responses and RGCs Apoptosis After Optic Nerve Crush by Modulating CD200/CD200R1 Interaction.

To explore the hypothesis that CD200Fc, a CD200R1 agonist with anti-inflammatory properties, will inhibit retinal glial cells hyperactivation and retinal ganglion cells (RGCs) apoptosis after optic nerve injury. CD200Fc was immediately administered after optic nerve crush (ONC) once by intravitreal injection. Rats were euthanized at 5 days after ONC. The density of RGCs was counted by immunostaining of retina flat mounts for Brn3a. TUNEL assay, immunoblotting analysis of ionized calcium-binding adapter molecule 1(iba1) (microglia marker) and glial fibrillary acidic protein (GFAP) (astrocytes and Müller cells marker), RT-PCR analysis of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin (IL)-8 and IL-10, ELISA measure protein levels of inflammatory cytokines and western blot analysis of CD200 and CD200R1 were evaluated. CD200Fc treatment suppressed ONC-induced RGCs loss through inhibition of RGCs apoptosis. Additionally, expression of glial cells activation markers GFAP and iba1 and production of pro-inflammatory cytokines (COX-2, iNOS, MCP-1, TNF-α, IL-8) were decreased in CD200Fc treated animals after ONC. Meanwhile, anti-inflammatory cytokine IL-10 was increased by CD200Fc treatment in ONC-induced rat retina. Finally, we found that CD200Fc significantly inhibited ONC-induced increased in expression of CD200 and raised the already high basal CD200R1 expression in the rat retina after ONC. Our results demonstrated that the anti-inflammatory effects of CD200Fc in ONC rats model through inhibited the activation of retinal glial cells via the interaction between CD200 and CD200R1, and the neuroprotective effects of CD200Fc on RGCs thought inhibited its apoptosis.

Interaction of Wip1 and NF-κB regulates neuroinflammatory response in astrocytes.

OBJECTIVE: The aims of the present study were to detect the interaction of Wip1 and NF-κB P65 in retina of an LPS-induced astrocytes activation model. METHODS: The interaction between Wip1 and nuclear factor kappa B (NF-κB) P65 was observed in lipopolysaccharide (LPS)-stimulated primary rat astrocytes derived from retina. The expressions of Wip1 and NF-κB P65 were evaluated using Western blot and RT-PCR. Small interfering RNA (siRNA) against Wip1 was transfected into astrocytes to clarify the phosphorylation status and nuclear translocation of NF-κB P65 and expressions of these proinflammatory factors. Meanwhile, expression of Wip1 was assessed following treatment with NF-κB inhibitor. RESULTS: Wip1 and phospho-NF-κB P65 (p-P65) expressions were significantly increased and colocalization in astrocytes after LPS treatment. The expression of p-P65 was augmented by transfected with Wip1 siRNA followed by LPS. Furthermore, pre-treatment with Wip1 siRNA further enhanced LPS-induced NF-κB P65 translocation into the nuclei and proinflammatory cytokine release. Finally, inhibition of NF-κB decreases Wip1 expression and transcription in primary astrocytes. CONCLUSION: These data provide a mechanism for the role for a negative feedback loop of Wip1 and NF-κB in LPS-induced astrocytic activation.

Expression of wild-type p53-induced phosphatase 1 in diabetic epiretinal membranes.

OBJECTIVE: The aims of the present study were to investigate the expression and distribution of Wild-type p53-induced phosphatase 1 (Wip1) in diabetic patients with proliferative diabetic retinopathy (PDR) with epiretinal membranes (ERMs) meanwhile analyze the colocalization of Wip1 and nuclear factor kappa-B (NF-κB) p65 in ERMs. METHODS: ERMs samples were collected from patients with PDR (PDR group) or non-diabetic patients with idiopathic epiretinal membranes (iERMs) (control group) during pars plana vitrectomy. Real-Time PCR analysis was carried out to examine the mRNA expression of Wip1 in ERMs. Immunohistochemical analysis and Immunofluorescent analysis were performed to detect the protein expression of Wip1 in ERMs. Double immunofluorescent staining was performed to detect the colocalization of Wip1 and glial fibrillary acidic protein (GFAP) (retinal glial cells marker), also Wip1 and NF-κB. RESULTS: ERMs were obtained from 17 eyes of 17 patients with PDR (the PDR group) and 9 eyes of 9 nondiabetic patients (the control group) with iERMs. Our results showed high expression levels of Wip1 mRNAs in ERMs after PDR, but low in iERMs. In addition, both immunohistochemistry and immunofluorescence assay showed strong immunoreactivity for Wip1 in PDR ERMs. Furthermore, Wip1 and GFAP were coexpressed in PDR membranes. Finally, the expression of Wip1 was paralleled with NF-κB. CONCLUSION: These data support the notion that Wip1 contributes to the formation of the ERMs in PDR membranes via NF-κB signaling.