Vitreous Olink proteomics reveals inflammatory biomarkers for diagnosis and prognosis of traumatic proliferative vitreoretinopathy.

Background: The aim of this study was to identify inflammatory biomarkers in traumatic proliferative vitreoretinopathy (TPVR) patients and further validate the expression curve of particular biomarkers in the rabbit TPVR model. Methods: The Olink Inflammation Panel was used to compare the differentially expressed proteins (DEPs) in the vitreous of TPVR patients 7-14 days after open globe injury (OGI) (N = 19) and macular hole patients (N = 22), followed by correlation analysis between DEPs and clinical signs, protein-protein interaction (PPI) analysis, area under the receiver operating characteristic curve (AUC) analysis, and function enrichment analysis. A TPVR rabbit model was established and expression levels of candidate interleukin family members (IL-6, IL-7, and IL-33) were measured by enzyme-linked immunosorbent assay (ELISA) at 0, 1, 3, 7, 10, 14, and 28 days after OGI. Results: Forty-eight DEPs were detected between the two groups. Correlation analysis showed that CXCL5, EN-RAGE, IL-7, ADA, CD5, CCL25, CASP8, TWEAK, and IL-33 were significantly correlated with clinical signs including ocular wound characteristics, PVR scoring, PVR recurrence, and final visual acuity (R = 0.467-0.699, p < 0.05), and all with optimal AUC values (0.7344-1). Correlations between DEP analysis and PPI analysis further verified that IL-6, IL-7, IL-8, IL-33, HGF, and CXCL5 were highly interactive (combined score: 0.669-0.983). These DEPs were enriched in novel pathways such as cancer signaling pathway (N = 14, p < 0.000). Vitreous levels of IL-6, IL-7, and IL-33 in the rabbit TPVR model displayed consistency with the trend in Olink data, all exhibiting marked differential expression 1 day following the OGI. Conclusion: IL-7, IL-33, EN-RAGE, TWEAK, CXCL5, and CD5 may be potential biomarkers for TPVR pathogenesis and prognosis, and early post-injury may be an ideal time for TPVR intervention targeting interleukin family biomarkers.

Relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment.

PURPOSE: To assess the relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment, and to analyze the relative factors in PDR eyes. METHODS: A total of 89 eyes, including 42 eyes with non-PDR (NPDR), and 47 eyes after vitrectomy with PDR were included and underwent OCTA. All images were processed by Python or FIJI. Multivariable linear regression models were used to analyze the associations between postoperative BCVA and OCTA parameters in PDR patients. RESULTS: Postoperative OCTA parameters including deep capillary plexus (DCP) parafoveal and perifoveal vessel density (VD), DCP parafoveal and perifoveal vessel length density (VLD), DCP fractal dimension (FD), choriocapillaris plexus (CCP) VD, CCP VLD, were significantly lower in the PDR group than in the NPDR group. In the superficial capillary plexus (SCP), we found a negative correlation between the postoperative BCVA and VD (parafovea: ß coefficient = -0.351, p = 0.023; perifovea: ß coefficient = -0.338, p = 0.036). Perifoveal VLD (ß coefficient = -0.343, p = 0.031) and FD (ß coefficient = -0.375, p = 0.016) of the SCP were also negatively correlated with postoperative BCVA. Regarding the DCP, perifoveal VD (ß coefficient = -0.396, p = 0.008), perifoveal VLD (ß coefficient = -0.334, p = 0.025), vessel tortuosity (VT) (ß coefficient = -0.369, p = 0.015) were negatively correlated with postoperative BCVA. In CCP, VLD (ß coefficient = -0.373, p = 0.023) and number of flow voids (ß coefficient = -0.334, p = 0.036) exhibited a negative association with postoperative BCVA. CONCLUSIONS: Postoperative BCVA of PDR patients was related to OCTA parameters of the SCP (parafoveal and perifoveal VD, perifoveal VLD and FD), DCP (perifoveal VD, VLD, and VT) and CCP (VLD and number of flow voids).

Early use of intravitreal triamcinolone to inhibit traumatic proliferative vitreoretinopathy: a randomised clinical trial.

AIMS: To evaluate the efficacy and safety of intravitreal triamcinolone acetonide (TA) injection at the end of emergency surgery for open globe injury (OGI) to suppress traumatic proliferative vitreoretinopathy (TPVR). METHODS: A single-centre, participant-masked, prospective, randomised controlled clinical trial. A total of 68 globe rupture patients with zone III were randomised to the control group (n=34) or the TA group (n=34) in 1:1 allocation ratio. Patients were treated with 0.1 mL TA in the TA group and 0.1 mL balanced salt solution in the control group at the end of emergency surgery. The primary outcome was the assessment of TPVR during vitrectomy 10±3 days later. Secondary outcomes included visual acuity (VA), retinal attachment rate, macular attachment rate, proliferative vitreoretinopathy (PVR) recurrent rate, side effects 6 months after vitrectomy. RESULTS: During vitrectomy, the TPVR grade of the control group was significantly more severe than the TA group (p=0.028). The TPVR score was significantly better in the TA group (9.30±0.82) than in the control group (6.44±1.06) (p=0.036). The final VA improved in 23 eyes (92%) in the TA group and in 14 eyes (63.64%) in the control group (p=0.008). The retinal attachment rates were 88% and 63.64% in the TA and control group, respectively (p=0.049). The two groups showed no significant difference in macular repositioning and PVR recurrent rate (p=0.215, 0.191). Temporary intraocular pressure elevation occurred in one eye in the TA group after emergency surgery. CONCLUSIONS: Early intravitreal TA injection for OGI effectively reduces TPVR, increases surgical success and improves visual prognosis.

The expression of miRNA-146a-5p and its mechanism of treating dry eye syndrome.

OBJECTIVE: Dry eye syndrome in which tear fluid quality or abnormality, or kinetic abnormality is caused by various reasons, resulting in decreased tear film stability. In recent years, more and more results from the studies indicate that miRNA alterations are involved in dry eye syndrome. And miRNA-146a-5p is a key regulator to regulate the inflammatory response. In this paper, we demonstrated whether miRNA-146a-5p could cure dry eye syndrome by regulating target genes based on network analysis. METHODS: In current study, we collected the blood of patients with dry eye disease served as a model group; the blood of healthy people was served as control group. The expression of miRNA-146a-5p in the patients was detected by RT-PCR, the genes controlled by miRNA-146a-5p were predicted by TargetScan, miRDB, miRWalk, and PicTar databases, and the genes regulated by miRNA-146a-5p which relative with dry eye disease were selected by drawing Venn diagram. RESULTS: The comparison of the general information between patients and healthy people was no significant difference, and it indicated that the two groups were comparable. The results of databases showed that IRAK1 was one of the target genes regulated by miRNA-146a-5p, and it is related to dry eye disease. The expression of miRNA-146a-5p was negatively related to IRAK1 mRNA and protein, while IRAK1 had a positive correlation with IL-6, TNF-α, and CBP proteins. CONCLUSION: These results emphasized that miRNA-146a-5p could inhibit the expression of IRAK1, IL-6, TNF-α, and CBP to help reduce the inflammatory response in dry eye syndrome.

Decreased Ratio of VEGF165b/VEGF in Aqueous Humor Predicts Progression of Diabetic Retinopathy.

BACKGROUND: Different splicing of vascular endothelial growth factor (VEGF) gene results in 2 families of VEGF, the proangiogenic isoforms (VEGFxxxa) and the antiangiogenic isoforms (VEGFxxxb). VEGF165b is the major antiangiogenic isoform of VEGF and the most studied member of the VEGFxxxb family so far. OBJECTIVES: To determine the concentration of VEGF165b and VEGF in the aqueous humor (AH) in diabetic eyes with or without diabetic retinopathy (DR) and to address the predictive value of VEGF165b/VEGF ratio for progression of DR. METHODS: AH samples from 20 eyes in healthy controls (CON group), 40 eyes in diabetic patients without DR (nDR group), and 30 eyes in diabetic patients with mild nonproliferative DR (DR group) were collected. All of the patients were followed up for at least 5 years. VEGF165b and VEGF levels of AH samples were measured by enzyme-linked immunosorbent assay (ELISA). The predictive value of the initial VEGF165b/VEGF ratio for progression of DR was studied. RESULTS: The mean concentration of VEGF165b significantly decreased in diabetic eyes vs. controls. The mean concentration of VEGF significantly increased in the DR group vs. the CON group. The VEGF165b/VEGF ratio was significantly lower in diabetic patients compared to the CON group. The VEGF165b/VEGF ratio was significantly lower in diabetic patients compared to the control group. The mean follow-up was 66.1months (range 60-71 months). The risk of DR progression was greater with a lower VEGF165b/VEGF ratio. CONCLUSION: The VEGF165b/VEGF ratio is lower in the AH of DR patients and the decreased ratio of VEGF165b/VEGF predicts DR progression.

Tumor Suppressor miR-184 Enhances Chemosensitivity by Directly Inhibiting SLC7A5 in Retinoblastoma.

The expression patterns and functional roles of miRNAs in retinoblastoma (RB) are poorly understood, especially those involved in chemoresistance. Here, we validated the expression pattern of 20 potential RB-suppressive miRNAs and confirmed that miR-184 is the most significantly decreased miRNA in human RB tissues, as well as chemoresistant cell line. Bioinformatic and molecular analyses revealed that SLC7A5 has three binding sites of miR-184 and significantly increased in RB tissues. miR-184 negatively correlated with SLC7A5 expression in RB tissues and mainly target position 2494-2513 of the SLC7A5 3'UTR to inhibit its expression. Furthermore, enforced expression of miR-184 reversed the oncogenic roles of SLC7A5 on proliferation, migration, and invasion of RB cells. In addition, miR-184 also enhances chemosensitivity of RB cells via inducing apoptosis and G2/M cell cycle arrest. Molecular studies revealed that miR-184-decreased phosphorylation status of known DNA damage repair sensors of the ATR/ATM pathways and induced persistent formation of γH2AX foci depend on targeting SLC7A5, leading to persistent DNA damage. Thus, targeting the miR-184/SLC7A5 pathway will provide new opportunities for drug development to reverse chemotherapeutic resistance in RB.

Cellular Blue Nevus of Perilimbal Conjunctiva: A Case Report and Review of Literature.

Cellular blue nevus is an uncommon neoplasm in the conjunctiva. Here we present an unusual case of a cellular blue nevus that clinically resembled conjunctival melanoma. A 29-year-old Chinese male was found to have a giant pigmented lesion of the conjunctiva around the limbal area of right eye from birth. Excisional biopsy with no-touch technique, lamellar corneal transplantation, amniotic membrane transplantation and adjuvant cryotherapy were performed. Histopathology revealed a nodular, well-defined tumor, which was composed of heavily pigmented dendritic cells and less pigmented spindle cells. There was no recurrence during eight years follow-up. Cellular blue nevus of conjunctiva can be wrongly diagnosed as conjunctival melanoma due to atypia criteria. Therefore, it is important to understand its clinical and pathological characteristics to avoid an overtreatment.

Secondary Sulcus-Fixed Foldable IOL Implantation with 25-G Infusion in Patients with Previous PPV after Open-Globe Injury.

PURPOSE: To evaluate the safety and efficacy of secondary sulcus-fixed foldable intraocular lens (IOL) implantation through a clear corneal incision with 25-G infusion in patients with previous pars plana vitrectomy (PPV) after open-globe injury, and to analyze postoperative outcomes and prognostic factors of treatment. METHODS: Clinical data of 89 eyes of 89 patients with open-globe injury who underwent secondary sulcus-fixed foldable IOL implantation through a clear corneal incision with 25-G infusion after vitrectomy in our hospital between January 2008 and June 2015 were retrospectively analyzed. The examinations before IOL implantation mainly included visual acuity, slit-lamp examination, direct and indirect ophthalmoscope, visual electrophysiology, corneal endothelium, B scan, ultrasound biomicroscope, and intraocular pressure. Five eyes underwent suturing of peripheral iris and 7 eyes underwent suturing of iris laceration simultaneously. The mean follow-up was 18 months with a range from 6 months to 8 years. RESULTS: The mean interval between secondary sulcus-fixed foldable IOL implantation and vitrectomy was 2.8 months with a range from 2 to 6 months. The uncorrected visual acuity improved in all patients with a well-centered IOL ranging from 0.1 to 0.8 with the best-corrected visual acuity from 0.1 to 1.0 after secondary IOL implantation. The postoperative complications mainly included mild anterior chamber exudates in 10 eyes (11%), temporary IOP elevation in 12 eyes (13%), and recurrent retinal detachment in 5 eyes (6%), which were subsequently managed by surgery. CONCLUSIONS: The interval of 2.8 months between vitrectomy and secondary IOL implantation is an appropriate and safe option to correct aphakia in patients receiving vitrectomy for open-globe injury.

The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy.

Corneal stromal fibrosis characterized by myofibroblasts and abnormal extracellular matrix (ECM) is usually the result of inappropriate wound healing. The present study tested the hypothesis that the ligand activation of peroxisome proliferator-activated receptor (PPAR) δ had antifibrosis effects in a rat model of corneal damage. Adult Sprague-Dawley rats underwent bilateral phototherapeutic keratectomy (PTK). The eyes were randomized into four groups: PBS, GW501516 (a selective agonist of PPARδ), GSK3787 (a selective antagonist of PPARδ), or GW501516 combined with GSK3787. The agents were subconjunctivally administered twice a week until sacrifice. The cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and postmortem histology. A myofibroblast marker (α-smooth muscle actin) and ECM production (fibronectin, collagen type III and collagen type I) were examined by immunohistochemistry and RT-PCR. At the early stages of wound healing, GW501516 inhibited reepithelialization and promoted angiogenesis. During the remodeling phase of wound healing, GW501516 attenuated the activation and proliferation of keratocytes, which could be reversed by GSK3787. GW501516 decreased transdifferentiation from keratocytes into myofibroblasts, ECM synthesis, and corneal haze. These results demonstrate that GW501516 controls corneal fibrosis and suggest that PPARδ may potentially serve as a therapeutic target for treating corneal scars.

[Role of endothelial progenitor cells in optic nerve injury of rats].

OBJECTIVE: To investigate the role of endothelial progenitor cells (EPC) in the injury of rat optic nerve. METHODS: An experimental study. The rat model of optic nerve injury was created by fluid percussion brain injury device (FPI). On hundred and eight rats (108 eyes) were divided into 2 groups randomly. Each group was further divided into 9 subgroups by the time of injury (24 h before and 3, 12, 24, 48, 72 h, 1, 2 and 3 weeks after the injury). The number of circulating EPCs was measured, HE staining of the optic nerve, immunohistochemistry study of CD31 (markers of vascular endothelial cells) and flash-visual evoked potential (F-VEP) were observed at every time point. Two independent sample t-test was used for the comparison between the control group and the optic nerve injury groups at the same time point. The correlation between different items was analyzed by Pearson test. P value less than 0.05 was considered significant. RESULTS: The number of EPCs in normal rats was 46-52/200 000 monocytes. After traumatic optic nerve injury, the number of EPCs was (34 ± 4, 34 ± 5, 69 ± 9, 76 ± 6, 107 ± 9, 69 ± 7, 58 ± 6 and 56 ± 4)/200 000 monocytes at 3, 12, 24, 48, 72 h, and 1, 2 and 3 weeks. The difference of number of EPCs between the experiment and control groups was significant at 3, 12, 24, 48, 72 h and 1 and 2 weeks after the injury (t = 5.29, 2.90, -4.30, -7.61, -14.17, -5.74 and -2.79; P < 0.05). The number of CD31(+) cell in the optic nerve and surround tissues in normal rats was (7-9)/5 high magnification field. After the injury, the number of CD31(+) cell was 8.36 ± 1.52, 7.17 ± 1.10, 10.41 ± 1.92, 11.43 ± 1.58, 14.29 ± 2.03, 17.33 ± 1.47, 17.86 ± 1.22 and 18.13 ± 1.40 at different time points. The difference of number of CD31(+) cell between the experiment and control groups was significant at 48, 72 h, and 1, 2, and 3 weeks after the injury (t = 4.31, -7.61, -8.17, -10.08, and -10.79; P < 0.05). The number of microvessels in the optic nerve and surround tissues in normal rats was 6-9/5 high magnification field. After traumatic optic nerve injury, the number of microvessels was 7.54 ± 2.01, 8.52 ± 2.21, 11.02 ± 1.62, 15.40 ± 2.04, 18.39 ± 1.96, 23.21 ± 1.50, 22.78 ± 2.40 and 24.13 ± 2.51 at different time points. The difference of number of microvessels between the experiment and control groups was significant at 48, 72 h, 1, 2, and 3 weeks after the injury (t = 4.25, -7.74, -8.26, -10.28 and -11.49; P < 0.05). The latency period of P waves was decreased at 3 h and increased to above basic level at 24 h, and then tend to be stable. The difference of latency period of P waves between the experiment and control groups was significant at 3, 12, 24, 48, 72 h, 1, 2 and 3 weeks after the injury (t = 4.15, 3.74, 5.84, 6.08, 6.40, 6.52, 6.53 and 6.61; P < 0.05). The amplitude of F-VEP was decreased at 3 h and increased to the basic level at 12 h, then decreased to below the basic level gradually. The difference of the amplitude of F-VEP between the experiment and control groups was significant at 3, 24, 48, 72 h, 1, 2 and 3 weeks after the injury (t = 3.95, 4.14, 5.26, 5.78, 6.49, 6.72 and 6.23; P < 0.05). The number of EPCs was correlated with the number of CD31(+) cell, microvessels and F-VEP (r = 0.43, 0.41 and 0.43; P < 0.01). CONCLUSIONS: The present study showed that the number of EPCs in the blood increases significantly after traumatic optic nerve injury, and the cells can arrive the traumatic area to repair injured tissue and enhance angiogenesis.

[Clinical study of ultrathin flap LASIK and LASEK for the treatment of high myopia with thin cornea].

OBJECTIVE: To explore the efficacy and safety of the ultrathin flap LASIK and LASEK for the treatment of high myopia with central corneal thickness below 500 microm. METHODS: Ultrathin flap LASIK and LASEK were randomly selected to treat high myopic patients with corneal thickness between 450 and 500 microm. 39 cases of 23 patients with average spherical equivalent of -7.51D (range from -6.00 to -9.50D) were treated with ultra thin flap LASIK, and 37 cases of 19 patients with average SE of -7.50D (range from -6.00 to -10.75D) were treated with LASEK. The uncorrected visual acuity, best corrected visual acuity, spherical equivalent, intraocular pressure, haze were examined and recorded 1, 3, 6 and 12 months postoperatively. RESULTS: Postoperative reaction was mild in LASIK patients, who showed a quick recovery in UCVA, whereas LASEK patients needed average 4 days to re-epithelization. At 1, 3, 6, 12 months postoperatively, the percentage of UCVA above 1.0 was 64.1%, 87.2%, 87.2% and 79.3% in LASIK patients and 37.8%, 75.7%, 67.6% and 71.4% in LASEK patients respectively. The percentage of spherical equivalent between +/- 0.50D was 48.7%, 51.3%, 61.5%, 82.8% in LASIK patients and 51.4%, 45.9%, 45.9%, 57.1% in LASEK respectively. There was no severe complications that implicate the BSCVA occurred in-operation and postoperatively. The main complications in LASIK group was corneal flap striae and overcorrection, regression and mild haze in LASEK group. CONCLUSION: Ultrathin flap LASIK had the similar efficacy and safety with LASEK in the treatment of high myopia with thin CCT, but the stability of results and satisfaction from the patients was superior to LASEK.

[Comparison of laser subepithelial keratomileusis and photorefractive keratectomy for the correction of myopia].

OBJECTIVE: To compare the effectiveness and difference between laser subepithelial keratomileusis (LASEK) and conventional photorefractive keratectomy (PRK) for the treatment of myopia up to -8.00 diopter. METHODS: In this prospective study, 46 patients with a manifest refactiion of -1.75 to -8.00 diopters were treated and followed up for 6 months. In each case, PRK was performed in one eye and LASEK in the other eye. The first eye treated and surgical method used in the first eye was randomized. Epithelial healing time, postoperative pain, uncorrected visual acuity (UCVA), manifest refraction, corneal HAZE were followed and compared in PRK and LASEK treated eyes. RESULTS: LASEK eyes took a mean time of 3.49 days to heal the epithelium, whereas PRK eyes took 2.45 days, which is statistically significant (P <0.05). Postoperative pain index was 2.04 and 2.45 in LASEK eyes and PRK eyes respectively (P <0.05). There were no significant differences between eyes in UCVA and manifest refraction during the follow time (P >0.05). However, LASEK-treated eyes showed less corneal haze than PRK eyes. CONCLUSIONS: LASEK can effectively and safely treat myopia up to -8.00 diopters as PRK did, and can diminish early pain after surgery and prevent corneal Haze from happening.