Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial.

BACKGROUND: We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. METHODS: A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. RESULTS: BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). CONCLUSIONS: We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. TRIAL REGISTRATION: The trail has been registered at Chinese Clinical Trail Registry( https://www.chictr.org.cn ) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy.

Purpose: To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). Methods: This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. Results: The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). Conclusion: Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).

Comparison of 27-gauge beveled-tip and 25-gauge flat-tip microincision vitrectomy surgery in the treatment of proliferative diabetic retinopathy: a randomized controlled trial.

PURPOSE: To compare the effectiveness and safety of a 27-gauge (27G) beveled-tip microincision vitrectomy surgery (MIVS) with a 25-gauge (25G) flat-tip MIVS for the treatment of proliferative diabetic retinopathy (PDR). METHODS: A prospective, single-masked, randomized, controlled clinical trial included 52 eyes (52 patients) with PDR requiring proliferative membrane removal. They were randomly assigned in a 1:1 ratio to undergo the 27G beveled-tip and or 25G flat-tip MIVS (the 27G group and the 25G group, respectively). During surgery, the productivity of cutting the membrane, the number of vitrectomy probe (VP) exchanges to microforceps, total operation time, vitrectomy time and intraoperative complications were measured. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) and postoperative complications were also assessed to month 6. RESULTS: Forty-seven eyes (47 patients) completed the follow-up, including 25 in the 27G group and 22 in the 25G group. During surgery in the 27G group, cutting the membrane was more efficient (P = 0.001), and the number of VP exchanges to microforceps was lower (P = 0.026). The occurrences of intraoperative hemorrhages and electrocoagulation also decreased significantly (P = 0.004 and P = 0.022). There were no statistical differences in the total operation time or vitrectomy time between the two groups (P = 0.275 and P = 0.372), but the former was slightly lower in the 27G group. Additionally, the 27G group required fewer wound sutures (P = 0.044). All the follow-up results revealed no significant difference between the two groups. CONCLUSIONS: Compared with the 25G flat-tip MIVS, the 27G beveled-tip MIVS could be more efficient in removing the proliferative membrane while reducing the occurrence of intraoperative hemorrhages and electrocoagulation using appropriate surgical techniques and instrument parameters. Its vitreous removal performance was not inferior to that of the 25G MIVS and might offer potential advantages in total operation time. In terms of patient outcomes, advanced MIVS demonstrates equal effectiveness and safety to 25G flat-tip MIVS. TRIAL REGISTRATION: The clinical trial has been registered at Clinicaltrials.gov (NCT0544694) on 07/07/2022. And all patients in the article were enrolled after registration.

Analysis of postoperative ocular surface changes and intervention effect after pars plana vitrectomy in meibomian gland dysfunction dry eye patients.

AIM: To observe ocular surface changes after phacovitrectomy in patients with mild to moderate meibomian gland dysfunction (MGD)-type dry eye and track clinical treatment response using a Keratograph 5M and a LipiView interferometer. METHODS: Forty cases were randomized into control group A and treatment group B; the latter received meibomian gland treatment 3d before phacovitrectomy and sodium hyaluronate before and after surgery. The average non-invasive tear film break-up time (NITBUTav), first non-invasive tear film break-up time (NITBUTf), non-invasive measured tear meniscus height (NTMH), meibomian gland loss (MGL), lipid layer thickness (LLT) and partial blink rate (PBR) were measured preoperatively and 1wk, 1 and 3mo postoperatively. RESULTS: The NITBUTav values of group A at 1wk (4.38±0.47), 1mo (6.76±0.70), and 3mo (7.25±0.68) were significantly lower than those of group B (7.45±0.78, 10.46±0.97, and 11.31±0.89; P=0.002, 0.004, and 0.001, respectively). The NTMH values of group B at 1wk (0.20±0.01) and 1mo (0.22±0.01) were markedly higher than those of group A (0.15±0.01 and 0.15±0.01; P=0.008 and P<0.001, respectively); however, there was no difference at 3mo. The LLT of group B at 3mo [91.5 (76.25-100.00)] significantly exceeded that of group A [65.00 (54.50-91.25), P=0.017]. No obvious intergroup difference was found in MGL or PBR (P>0.05). CONCLUSION: Mild to moderate MGD dry eye worsens in the short term after phacovitrectomy. Preoperative cleaning, hot compresses, and meibomian gland massage as well as preoperative and postoperative sodium hyaluronate promote the rapid recovery of tear film stability.

Negative effects of enlarging internal limiting membrane peeling for idiopathic macular hole surgery.

AIM: To observe the effects of the different extents of internal limiting membrane (ILM) peeling on the surgical success and anatomical and functional outcomes of idiopathic macular hole (IMH). METHODS: In this retrospective cohort study, 36 patients were reviewed and divided into two groups according to the extent of ILM peeling: group A (18 patients), with the peeling area within one-half of the optic disc macular distance as the radius; group B (18 patients), with the peeling area larger than that of group A but did not exceed the optic disc macular distance as the radius. The main outcomes included the best corrected visual acuity (BCVA), light-adaptive electroretinography, macular hole (MH) closure rate, central macular thickness (CMT), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness [nine regions based on the Early Treatment of Diabetic Retinopathy Study (ETDRS) ring] before and 1, 3, and 6mo after surgery. RESULTS: The closure rate was 94.4% (17/18) both in groups A and B. The BCVA in both groups improved significantly compared with the preoperative values, but there was no difference between the two groups. The b-wave amplitude of the electroretinogram analysis was significantly improved in both groups compared to that of the preoperative period, with a greater increase in group A than in group B at 6mo (P=0.017). The CMT in both groups gradually decreased after surgery, and there was no difference between the two groups. The RNFL thickness of the temporal outer ring region in group B was significantly lower than that in group A at 3 and 6mo after surgery (P=0.010, 0.032). The GCC thickness of the temporal outer ring region in group B was significantly lower than that in group A at 6mo after surgery (P=0.038). CONCLUSION: Enlarging the extent of ILM peeling doesn't affect the IMH closure rate and visual acuity recovery, but the greater the extent of peeling, the greater the damage to the inner retinal structures.

PSF functions as a repressor of hypoxia-induced angiogenesis by promoting mitochondrial function.

BACKGROUND: Abnormal neovascularization is the most common cause of blindness, and hypoxia alters tissue metabolism, function, and morphology. HIF-1α, the transcriptional activator of VEGF, has intricate mechanisms of nuclear translocation and activation, but its signal termination mechanisms remain unclear. METHODS: We investigated the role of polypyrimidine tract-binding protein-associated splicing factor (PSF) in cellular energy production, migration, and proliferation by targeting HIF-1α in vivo and in vitro PSF plasmids were transfected with liposome 2000 transfection reagent. Young C57/BL6J mice were kept in a hyperoxia environment, followed by indoor air, resulting in oxygen-induced retinopathy. Oxygen-induced retinopathy (OIR) animals were randomly divided into three groups: OIR group, OIR + vector group (OIR cubs treated with rAAV vector) and OIR + PSF group (OIR cubs treated with rAAV-PSF). Age-matched C57/BL6J mice were used as controls and exposed to constant normoxic conditions. The animals were executed and their pupils were subjected to subsequent experiments. The metabolic spectrum was analyzed by Seahorse XFe96 flux analyzer, and OCR and extracellular acidification rate were quantified at the same time. RESULTS: PSF ameliorated retinal neovascularization and corrected abnormal VEGF expression in mice with oxygen-induced retinopathy and reduced intra-retinal neovascularization in Vldlr - / - mice. PSF reprogrammed mitochondrial bioenergetics and inhibited the transition of endothelial cells after hypoxia, suggesting its involvement in pathological angiogenesis.Ectopic PSF expression inhibited hypoxia-induced HIF-1α activation in the nucleus by recruiting Hakai to the PSF/HIF-1α complex, causing HIF-1α inhibition. PSF knockdown increased hypoxia-stimulated HIF-1α reactions. These hypoxia-dependent processes may play a vital role in cell metabolism, migration, and proliferation. Thus, PSF is a potential treatment target in neovascularization-associated ophthalmopathy. CONCLUSION: This is the first study showing that PSF inhibits HIF-1α via recruitment of Hakai, modulates mitochondrial oxidation and glycolysis, and downregulates VEGF expression under hypoxia. We propose a new HIF-1 α/Hakai regulatory mechanism that may play a vital role in the pathogenesis of neovascularization in ophthalmopathy. PSF-Hakai-HIF-1α signaling pathway under hypoxia condition. Schematic diagram showing that the PSF-Hakai-HIF-1α signaling pathway. Under hypoxia condition, PSF-Hakai complex regulate HIF-1α signaling, thus inhibiting downstream target gene VEGF, cell metabolism and angiogenesis eventually. Video Abstract: Detailed information of Materials and Methods.

Refractive outcomes after vitrectomy combined with phacoemulsification of idiopathic macular holes.

AIM: To report the refractive outcomes after vitrectomy combined with phacoemulsification and intraocular lens (IOL) implantation (phaco-vitrectomy) in idiopathic macular holes (IMH). METHODS: A total of 56 eyes with IMH (IMH group) that underwent phaco-vitrectomy and 44 eyes with age-related cataract (ARC group) that underwent cataract surgery were retrospectively reviewed. The best corrective visual acuity (BCVA), predicted refractive error (PRE), actual refractive error (ARE), axial length (AL), were measured in both groups before and 6mo after operation. The power calculation of IOL and the predicted refractive error (PRE) were calculated according to the SRK/T formula. The difference of PRE and ARE between the two groups were compared and analyzed. RESULTS: In the IMH group, the diameters of macular holes were 271.73±75.85 µm, the closure rate was 100%. The pre- and post-operative BCVA were 0.80±0.35 and 0.40±0.35 logMAR. The PRE of A-ultrasound and IOL Master in the IMH group was -0.27±0.25 and 0.10±0.66 D. The postoperative mean absolute prediction error (MAE) was observed to be 0.58±0.65 and 0.53±0.37 D in the IOL Master and A-ultrasound (P=0.758). The PRE and ARE of the IMH group were 0.10±0.66 D and -0.19±0.64 D (P=0.102). The PRE and ARE of the ARC group was -0.43±0.95 and -0.31±0.93 D (P=0.383). The difference between PRE and ARE was -0.33±0.81 and 0.09±0.64 D in the IMH and ARC groups (P=0.021). The proportion of myopic shift was 67.9% in the IMH group and 27.3% in the ARC group (P=0.004). CONCLUSION: The myopic shift can be observed in patients with IMH after phaco-vitrectomy.

Target-triggered entropy-driven amplification system-templated silver nanoclusters for multiplexed microRNA analysis.

MicroRNAs (miRNAs) are important biomarkers for the diagnosis, prognosis, and treatment of human diseases. Sensitive and selective detection of multiple miRNAs simultaneously will greatly facilitate the early and accurate diagnosis of cancers. Herein, a novel entropy-driven amplification system-templated silver nanoclusters sensing platform was developed for the multiplexed analysis of tumor-associated miRNAs. The sensing platform was constructed by coupling target-triggered entropy-driven catalysis with luminescence adjustable DNA-templated silver nanoclusters (Ag NCs). In the presence of target miRNA, the sensing platform initiates the branch migration and strand displacement of the complex, which has a six-base cytosine loop for stabilizing the luminous Ag NCs. The target is cyclically generated for new catalysis while turning off the fluorescence of Ag NCs; this is accompanied by a significantly amplified optical readout. In this study, two different complex-stabilized Ag NCs systems were proposed, the yellow-emitting Ag NCs and red-emitting Ag NCs biosensors enabled the analysis of miRNA-141 and miRNA-155 with detection limits of 6.1 pM and 8.7 pM, respectively. Impressively, owing to the excellent selectivity, flexibility, and narrow-band excitation of the platform, the multiplexed synchronous detection of miRNA-141 and miRNA-155 were achieved in buffer, biological cell lysates and human serum samples with satisfactory results. The simple, flexible, and convenient strategy provides a powerful tool for multiple biomarkers analysis and related clinical applications.

Development and Application of Aptamer-Based Surface-Enhanced Raman Spectroscopy Sensors in Quantitative Analysis and Biotherapy.

Surface-enhanced Raman scattering (SERS) is one of the most special and important Raman techniques. An apparent Raman signal can be observed when the target molecules are absorbed onto the surface of the SERS substrates, especially on the "hot spots" of the substrates. Early research focused on exploring the highly active SERS substrates and their detection applications in label-free SERS technology. However, it is a great challenge to use these label-free SERS sensors for detecting hydrophobic or non-polar molecules, especially in complex systems or at low concentrations. Therefore, antibodies, aptamers, and antimicrobial peptides have been used to effectively improve the target selectivity and meet the analysis requirements. Among these selective elements, aptamers are easy to use for synthesis and modifications, and their stability, affinity and specificity are extremely good; they have been successfully used in a variety of testing areas. The combination of SERS detection technology and aptamer recognition ability not only improved the selection accuracy of target molecules, but also improved the sensitivity of the analysis. Variations of aptamer-based SERS sensors have been developed and have achieved satisfactory results in the analysis of small molecules, pathogenic microorganism, mycotoxins, tumor marker and other functional molecules, as well as in successful photothermal therapy of tumors. Herein, we present the latest advances of the aptamer-based SERS sensors, as well as the assembling sensing platforms and the strategies for signal amplification. Furthermore, the existing problems and potential trends of the aptamer-based SERS sensors are discussed.

Interactions of Transition Metal Dichalcogenide Nanosheets With Mucin: Quartz Crystal Microbalance With Dissipation, Surface Plasmon Resonance, and Spectroscopic Probing.

Ultrathin 2-dimensional transition metal dichalcogenides (TMDs) have become a class of high-potential materials in biomedicine due to their intriguing properties. They have been applied to solve biomedical challenges, such as biosensing, bioimaging, drug delivery, and cancer therapy. However, studies of the interactions between these materials and biomolecules are insufficient. Mucous tissue serves as a barrier to foreign hazardous substances and a gel layer for substance exchange. The main organic matter of mucous tissue is mucin, so it was selected as a model biomolecule to study its interactions with six different TMD nanosheets (NSs), including single-layered (SL), few-layered (FL), and small few-layered (SFL) MoS2 and WS2 NSs, using quartz crystal microbalance (QCM) with a dissipation monitor (QCM-D) and surface plasmon resonance (SPR). Additionally, UV absorption, fluorescence, and circular dichroism (CD) spectroscopy were applied to investigate the mechanism of the interactions and to study the conformational change of mucin. We found that the TMD NSs could adsorb on the mucin layer and affect its viscoelasticity. The results indicated that the SL WS2 NSs exhibited the highest initial absorption rate and the maximum absorption amount, while the SL MoS2 NSs exhibited the highest initial desorption rate. During the adsorption, the viscoelasticity variations of the mucin layer caused by the WS2 nanosheets were weaker than those caused by the MoS2 nanosheets. Furthermore, the conformational changes of mucin caused by the SL MoS2, SL WS2, and SFL MoS2 NSs were higher than those resulting from other TMD NSs. These findings provide important information on the interactions between TMD NSs and mucin and provide useful insights into the interfacial behavior of TMD NSs before they enter tissues.

Superior Antifouling Performance of a Zwitterionic Peptide Compared to an Amphiphilic, Non-Ionic Peptide.

The aim of this study was to explore the influence of amphiphilic and zwitterionic structures on the resistance of protein adsorption to peptide self-assembled monolayers (SAMs) and gain insight into the associated antifouling mechanism. Two kinds of cysteine-terminated heptapeptides were studied. One peptide had alternating hydrophobic and hydrophilic residues with an amphiphilic sequence of CYSYSYS. The other peptide (CRERERE) was zwitterionic. Both peptides were covalently attached onto gold substrates via gold-thiol bond formation. Surface plasmon resonance analysis results showed that both peptide SAMs had ultralow or low protein adsorption amounts of 1.97-11.78 ng/cm2 in the presence of single proteins. The zwitterionic peptide showed relatively higher antifouling ability with single proteins and natural complex protein media. We performed molecular dynamics simulations to understand their respective antifouling behaviors. The results indicated that strong surface hydration of peptide SAMs contributes to fouling resistance by impeding interactions with proteins. Compared to the CYSYSYS peptide, more water molecules were predicted to form hydrogen-bonding interactions with the zwitterionic CRERERE peptide, which is in agreement with the antifouling test results. These findings reveal a clear relation between peptide structures and resistance to protein adsorption, facilitating the development of novel peptide-containing antifouling materials.

[In vivo high-resolution imaging of rat retina with optical coherence tomography and the expression of Bcl-2, Bax, Caspase-3 mRNA during critical period plasticity].

OBJECTIVE: To observe the changes of retinal thickness during critical period plasticity in rat, and to investigate whether apoptosis participates in the structural forming of retina. METHODS: Experimental research. 50 normal newborn pups of SD rat were randomly selected in the experiment. In vivo consecutive scanning of retinal image was taken and the retinal thickness from RPE to ILM was recorded in 10 pups (20 eyes) with spectral domain optical coherence tomography (OCT) at postnatal day 14 (P14), P18, P21, P24 and P42. Bcl-2, Bax, Caspase-3 mRNA was assessed with fluorescent quantitative real-time polymerase chain reaction after total RNA extracted from 4 retinas of 2 pups at each time point from P14 to P42. Histological measurement of retinal thickness of sections with HE staining from 4 pups (8 eyes) at each time point was compared with the results of OCT scanning. TUNEL staining was used to detect the apoptotic cells in retinal cryosections of 2 pups (4 eyes) at the same time point. The data were analyzed by One-way ANOVA and Linear Regression through SPSS 11.5 software. RESULTS: There was significant difference between the retinal thickness measured through OCT in pups from P14 to P42 (F = 15.425, P = 0.001). And the values were (243.42 ± 13.83) µm at P14, (218.78 ± 8.21) µm at P18, (195.42 ± 8.02) µm at P21, (195.74 ± 14.85) µm at P24, (190.79 ± 11.70) um at P42. The retinal thickness measured through OCT decreased significantly during the first 3 weeks after birth. The results of OCT measurement had linear correlation with histology measurement (R = 0.794, P = 0.000). There was significant difference between mRNA expression of Bcl-2, Bax and Caspase-3 in pups from P14 to P42 (F = 18.684, F = 47.307, F = 49.611; P = 0.000). The relative expression of Bax and Caspase-3 peaked at P24 while Bcl-2 was much more stable. There were a lot of apoptotic cells in the ganglion cells layer, the inner nuclear layer and the outer nuclear layer during P18 to P24 by TUNEL staining. And the apoptosis alleviated at P42. CONCLUSIONS: The retinal thickness decreases when the retina continues to develop during critical period plasticity. Cirrus HD-OCT can be used as an effective instrument to show the layers of retina in rat in vivo. Apoptosis participates in the course of retinal development which possibly leads to the thinning of retina.