Keratoconus: exploring fundamentals and future perspectives - a comprehensive systematic review.

Background: New developments in artificial intelligence, particularly with promising results in early detection and management of keratoconus, have favorably altered the natural history of the disease over the last few decades. Features of artificial intelligence in different machine such as anterior segment optical coherence tomography, and femtosecond laser technique have improved safety, precision, effectiveness, and predictability of treatment modalities of keratoconus (from contact lenses to keratoplasty techniques). These options ingrained in artificial intelligence are already underway and allow ophthalmologist to approach disease in the most non-invasive way. Objectives: This study comprehensively describes all of the treatment modalities of keratoconus considering machine learning strategies. Design: A multidimensional comprehensive systematic narrative review. Data sources and methods: A comprehensive search was done in the five main electronic databases (PubMed, Scopus, Web of Science, Embase, and Cochrane), without language and time or type of study restrictions. Afterward, eligible articles were selected by screening the titles and abstracts based on main mesh keywords. For potentially eligible articles, the full text was also reviewed. Results: Artificial intelligence demonstrates promise in keratoconus diagnosis and clinical management, spanning early detection (especially in subclinical cases), preoperative screening, postoperative ectasia prediction after keratorefractive surgery, and guiding surgical decisions. The majority of studies employed a solitary machine learning algorithm, whereas minor studies assessed multiple algorithms that evaluated the association of various keratoconus staging and management strategies. Last but not least, AI has proven effective in guiding the implantation of intracorneal ring segments in keratoconus corneas and predicting surgical outcomes. Conclusion: The efficient and widespread clinical translation of machine learning models in keratoconus management is a crucial goal of potential future approaches to better visual performance in keratoconus patients. Trial registration: The article has been registered through PROSPERO, an international database of prospectively registered systematic reviews, with the ID: CRD42022319338.

Keratoconus: from fundamentals to future Artificial intelligence has changed how we treat the eye disease keratoconus in recent years. This study examines the many keratoconus therapies available, including surgery and contact lens wear, and how artificial intelligence can improve the safety and accuracy of these procedures. We combed through numerous papers to locate this data. To achieve the best outcomes, several parameters and methods should be evaluated. According to the study, some elements from eye scans are more useful than others. The idea behind using artificial intelligence is to help patients see better and treat keratoconus more effectively.

New advances in medical management of dry eye: optimizing treatment strategies for enhanced relief.

PURPOSE: Dry eye disease (DED) is a prevalent ocular surface disease that is conventionally characterized by tear film hyperosmolarity and instability. This review presents a summarized classification of DED, followed by a comprehensive discussion of the most recent topical and systemic medications and clinical recommendations for selecting the most appropriate option for each patient. METHODS: An extensive literature search was conducted on electronic databases, such as PubMed, Scopus, and Web of Science, using keywords including "dry eye syndrome," "ocular surface disease," "medical management," "artificial tears," "topical immunomodulators," and "meibomian gland dysfunction." RESULTS: The underlying reasons for DED can range from insufficient aqueous tear production to increased tear evaporation. Recent literature has provided a more in-depth understanding of the pathophysiology of DED by examining the tear film's lipid, aqueous, and mucin layers. However, despite these advancements, medical management of patients with symptomatic DED has not fully reflected this modernized knowledge of its pathophysiology. CONCLUSION: To develop a rationalized strategy for treating DED, it is crucial to have updated knowledge of therapeutic options, their mechanisms of actions, and indications based on the DED type and underlying causes.

An Overview of Surgical Approaches for Lower Eyelid Blepharoplasty.

Age-related changes in the lower eyelid are noticed by patients as bags or circles under the eye, a tired look, and a flattened face. Lower eyelid blepharoplasty, in which the excess skin and/or orbital fat is excised and repositioned, is mainly performed for aesthetic reasons rather than the correction of functional abnormalities. Favorable outcomes for the combination of these approaches have been reported, but the most suitable surgical technique is still debated. This systematic narrative review deals with the indications, preoperative considerations, operative techniques, and complications of several different surgical approaches to lower eyelid blepharoplasty.

Genetic predisposition to ocular surface disorders and opportunities for gene-based therapies.

The ocular surface, comprised of the corneal and conjunctival epithelium, innervation system, immune components, and tear-film apparatus, plays a key role in ocular integrity as well as comfort and vision. Gene defects may result in congenital ocular or systemic disorders with prominent ocular surface involvement. Examples include epithelial corneal dystrophies, aniridia, ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, xeroderma pigmentosum (XP), and hereditary sensory and autonomic neuropathy. In addition, genetic factors may interact with environmental risk factors in the development of several multifactorial ocular surface disorders (OSDs) such as autoimmune disorders, allergies, neoplasms, and dry eye disease. Advanced gene-based technologies have already been introduced in disease modelling and proof-of-concept gene therapies for monogenic OSDs. For instance, patient-derived induced pluripotent stem cells have been used for modelling aniridia-associated keratopathy (AAK), XP, and EEC syndrome. Moreover, CRISPR/Cas9 genome editing has been used for disease modelling and/or gene therapy for AAK and Meesmann's epithelial corneal dystrophy. A better understanding of the role of genetic factors in OSDs may be helpful in designing personalized disease models and treatment approaches. Gene-based approaches in monogenic OSDs and genetic predisposition to multifactorial OSDs such as immune-mediated disorders and neoplasms with known or possible genetic risk factors has been seldom reviewed. In this narrative review, we discuss the role of genetic factors in monogenic and multifactorial OSDs and potential opportunities for gene therapy.

Mustard Gas-Induced Ocular Surface Disorders: An Update on the Pathogenesis, Clinical Manifestations, and Management.

PURPOSE: Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries. METHODS: Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022. Data were collected by using keywords: "mustard gas" OR "sulfur mustard" AND "eye" OR "cornea" OR "ocular complication" OR "keratitis" OR "keratopathy" OR "limbal stem cell deficiency" OR "dry eye." RESULTS: Chronic intracellular toxicity, inflammation, and ischemia have been shown to play an essential role in the pathogenesis of MG injury. Ocular surface injuries can have acute, chronic, and most distinctly a delayed-onset presentation leading to various degrees of limbal stem cell deficiency. To date, no treatment has been agreed on as the standard treatment for chronic/delayed-onset MG keratopathy. Based on the authors' experience, we propose a management algorithm for MG-related ocular surface injuries involving optimization of ocular health, anti-inflammatory therapy, and if needed surgical interventions. The management of chronic and delayed-onset presentation remains challenging. CONCLUSIONS: MG keratopathy is a unique form of chemical injury which can lead to a range of ocular surface pathologies. Long-term anti-inflammatory therapy even in patients with seemingly mild disease may potentially reduce the likelihood of the development of more severe delayed-onset disease.

Mini-Conjunctival Limbal Autograft (Mini-CLAU) Using Platelet-Rich Plasma Eye Drops (E-PRP): A Case Series.

PURPOSE: The purpose of this study was to introduce a new method of limbal stem cell transplantation using autologous platelet-rich plasma (E-PRP) eye drops for unilateral total limbal stem cell deficiency. METHODS: Patients with total unilateral limbal stem cell deficiency due to chemical burn underwent mini-conjunctival limbal autograft using autologous E-PRP drops. One small limbal block, measuring 2 × 2 mm, was harvested from the patients' contralateral healthy eye and transplanted to the diseased eye. All patients received E-PRP drops until achieving complete corneal epithelialization. Subsequent corneal transplantation was performed in eyes with significant stromal opacification. Corneal buttons obtained during corneal transplantation underwent immunohistochemistry for the evaluation of limbal stem cell markers (ABCG2 and P63). Visual acuity, epithelial healing, corneal clarity, and regression of corneal conjunctivalization/vascularization were evaluated after surgery. RESULTS: Ten patients with acid (n = 7) or alkali (n = 3) burn were included. The mean follow-up period was 21.7 ± 5.8 months (range, 12-32 months). Corneas were completely reepithelialized within 14.9 ± 3.5 days (range, 11-21 days). Corneal conjunctivalization/vascularization dramatically regressed 1 to 2 months after surgery in all cases, and corneal clarity considerably improved in 7 patients. In the 3 eyes with significant stromal opacification, subsequent optical penetrating keratoplasty was performed. The ocular surface was stable throughout the follow-up period in all eyes. BSCVA improved to 0.60 ± 0.0.32 and 0.46 ± 0.0.25 logMAR in eyes with and without corneal transplantation, respectively, at the final follow-up visit. ABCG2 and P63 markers were detected on corneal buttons after keratoplasty. CONCLUSIONS: Based on our clinical and laboratory findings, mini-conjunctival limbal autograft using E-PRP can be considered as a promising alternative to ocular surface reconstruction.

Association of 2 Lysyl Oxidase Gene Single Nucleotide Polymorphisms with Keratoconus: A Nationwide Registration Study.

Purpose: Keratoconus (KC) is the most common primary ectatic corneal disease, characterized by progressive thinning of the cornea, affecting its shape and structure and leading to visual loss. Lysyl oxidase is an important component of the extracellular matrix and contributes to the homeostasis of corneal stromal extracellular matrix via enzymatic reaction. This nationwide registration study aims to examine the association of KC with 2 known single nucleotide polymorphisms, rs2956540 and rs10519694, in a population of Iranian descent. Design: Case-control. Participants: One hundred seventy-eight subjects with KC and 180 clinically healthy subjects participated in the study. Methods: Genomic DNA was extracted from peripheral blood samples, and their genotypes were determined using tetra-primer amplification refractory mutation system-polymerase chain reaction. Main Outcome Measures: Allele frequency for rs2956540 and rs10519694. Results: Genotype frequency was significantly different between cases and controls for rs2956540 (P value = 0.019). The rs2956540 C allele carriers were significantly more frequent among KC cases than healthy controls (P valuechi-square = 0.015, P valueFisher exact = 0.017). There was a significant difference in genotype frequency between groups for rs10519694 (P value = 0.001). T allele carriers were significantly more frequent among KC patients (P valuechi-square = 0.002, P valueFisher exact = 0.001). Sex stratification revealed no significant differences in genotype frequency between males and females in cases and controls. Fitting the general linear model showed that rs10519694 could be considered a predictor for the development of KC (P value = 0.001); however, this was not observed for rs2956540 (P value = 0.323). Conclusions: rs2956540 and rs10519694 are associated with KC in a population of Iranian descent. rs10519694 could potentially be used for KC risk prediction.

The Association Between Computerized Tomography Findings and Ocular Trauma Score in Open Globe Injury: The Prognostic Value of Imaging.

PURPOSE: The aim of this study was to evaluate the association between CT findings and Ocular Trauma Score (OTS) in open globe injury. METHODS: In 182 eyes with open globe injury, CT findings were categorized into 5 major types: scleral irregularity with decreased globe volume, dislocation of the crystalline lens, abnormal vitreous density, thickening of the chorioretinal layer, and intraocular foreign body/air. Association between different types and number of CT findings with OTS stages were evaluated through a multivariate analysis. RESULTS: Mean age of the patients was 38 ± 8.5 years. The most common CT findings were severe scleral irregularity or globe collapse (71.9%) and abnormal vitreous density (56%). The most common OTS stages were II (44.5%) and I (30.7%). In multivariate analysis, abnormal vitreous density (odds ratio [OR] = 2.11, p < 0.001), chorioretinal thickening (OR = 1.89, p < 0.001), and intraocular foreign body/air (OR = 1.58, p = 0.001) were associated with more advanced OTS stages (I or II). Mean OTS in eyes with 1, 2, and 3 CT findings were 66 (stage III), 47 (stage II), and 37 (stage I), respectively ( p value = 0.008). Presence of 2 (OR = 2.46, p < 0.001) and 3 (OR = 2.92, p < 0.001) CT findings were associated with more advanced OTS stages (I or II). CONCLUSIONS: The type and number of CT findings may help to predict the OTS stage and visual prognosis in eyes with open globe injury.

Improving the properties of fish skin collagen/silk fibroin dressing by chemical treatment for corneal wound healing.

Natural biomaterials are crucial in ocular tissue engineering because they allow cells to proliferate, differentiate, and stratify while maintaining the typical epithelial phenotype. In this study, membranes as dressings were formed from silk fibroin and collagen (Co) extracted from fish skin and then modified with carbodiimide chemical cross linker in different concentrations. The samples were evaluated by different analyses such as structural, physical (optical, swelling, denaturation temperature, degradation), mechanical, and biological (viability, cell adhesion, immunocytochemistry) assays. The results showed that all membranes have excellent transparency, especially with higher silk fibroin content. Increasing the cross linker concentration and the ratio of silk fibroin to Co increased the denaturation temperature and mechanical strength and, conversely, reduced the degradation rate and cell adhesion. The samples did not show a significant difference in toxicity with increasing cross linker and silk fibroin ratio. In general, samples with a low silk fibroin ratio combined with cross linker can provide desirable properties as a membrane for corneal wound healing.

Role of Blepharoexfoliation in Demodex Blepharitis: A Randomized Comparative Study.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of blepharoexfoliation in the treatment of Demodex blepharitis. METHODS: Patients with microscopically approved Demodex blepharitis were enrolled. Patients in the treatment group were treated once with in-office blepharoexfoliation (BlephEx LLC; Franklin, TN) using tea tree oil 2% shampoo, followed by eyelid scrubs with tea tree oil 2% shampoo twice a day for 8 weeks. Patients in the control group were treated with the same protocol, except for the in-office sham blepharoexfoliation procedure. As the main outcome measurement, the changes in the severity of symptoms [Ocular Surface Disease Index (OSDI) score] were compared. The changes in Demodex count and meibomian gland dysfunction (MGD) severity were compared as the secondary outcome measurements. RESULTS: Eighty-one patients (36 male and 45 female) were included. The mean age of the patients was 53.56 ± 8.13 years. The mean baseline OSDI score was 33.30 ± 11.80. The mean baseline Demodex count was 4.84 ± 1.49. The Demodex count at the baseline visit was moderately correlated with the baseline OSDI score (R = 0.526, P = 0.011) and baseline MGD severity ( P = 0.02). At the 8-week visit, the OSDI score was 22.62 ± 8.23 and 27.09 ± 9.11 in the blepharoexfoliation and control groups, respectively ( P = 0.016). At the 8-week visit, the Demodex count was 2.6 ± 1.08 and 3.03 ± 1.27 in the treatment and control groups, respectively ( P = 0.025). MGD improved in both groups ( P = 0.84). In the blepharoexfoliation group, the change in the OSDI score was moderately correlated with the baseline OSDI score (R = 0.611, P = 0.01). CONCLUSIONS: One session of blepharoexfoliation, followed by manual eyelid scrubs was more effective than eyelid scrubs alone in reducing patients' symptoms and Demodex count.

The Ability of Antibody against Truncated Matrix Metalloproteinase 9 Peptide to Evaluate the Native Protein on Tear Drops of Dry Eye Disease Patients by a Point-of-Care Diagnostic System.

Purpose: To obtain a reactive and specific antibody against truncated matrix metalloproteinase 9 (MMP-9), that has reactivity toward the native protein. Precision, accuracy, specificity, and sensitivity were evaluated using a point-of-care test. Methods: An in silico study was used to confirm the anti peptide truncated MMP-9 is against native MMP-9. After an antibody titer assessment, purification, and characterization, the anti MMP-9 was assessed. The cut-off value was determined using the purified gelatinases of the supernatant HCT 116 cell line. The supernatant was purified by preparative native-polyacrylamide gel electrophoresis based on charge and size of the proteins. Furthermore, quality control (QC) of the results were performed following standard densitometry methods. Results: A truncated MMP-9 is the major epitope peptide that can trigger the immune system to scavenge for a specific and reactive antibody against the native MMP-9. The MMP-9 native protein is purified from the supernatant of the HCT 116 cell line and the commercially available, full-length MMP-9. The cut-off value was estimated at 30 µg/mL. QC results indicated that the specificity was 80%, sensitivity was 96.7%, accuracy was 91%, and precision was 91.66%. The area under curve was 0.827 (P < 0.001). The positive predictive value was 83%, and the negative predictive value was 96%. Conclusions: The antibody against the synthetic epitope peptide can detect the native MMP-9. Native MMP-9 is considered the main biomarker in an immunoassay POCT and is used to diagnose dry eye disease (DED). In accordance with QC results, MMP-9 point of care test can be utilized for screening patients suffering from DED.

Promoting keratocyte stem like cell proliferation and differentiation by aligned polycaprolactone-silk fibroin fibers containing Aloe vera.

There is a long history behind applying biological macromolecules like Aloe vera (AV) in regenerative medicine; endowed with anti-inflammatory and antimicrobial activities besides improving immune activity, AV has always been of particular interest to regenerate/reconstruct injuries and burns. In the present study, aligned electrospun polycaprolactone (PCL)-silk fibroin (SF) fibers containing different percentages of AV (0, 2.5, 5, and 7.5%wt) were fabricated for stromal regeneration. The results illustrated that a uniform bead-free structure was obtained, and the AV incorporation decreased the mean fiber diameter from 552 down to 182 nm and led to more alignment in the fibers. The Young's modulus raised from 4.96 to 5.26 MPa by higher amount of AV up to 5%wt. It is noteworthy that both the fiber alignment and AV affected the scaffolds' transparency and water uptake to increase. The human stromal keratocyte cells (hSKC)s culture revealed that the addition of AV and morphological properties of scaffolds encouraged cell adhesion and proliferation. The mRNA expression level for keratocan and ALDH3A1 and immunocytochemistry F-actin revealed the positive effect of AV on hSKCs differentiation. Our study indicated the promising potential of AV as a biological macromolecule for stromal tissue regeneration.

Topography versus non-topography-guided photorefractive keratectomy with corneal cross-linking variations in keratoconus.

AIM: To compare the visual results of non-topography-guided and topography-guided photorefractive keratectomy (PRK) applying sequential and simultaneous corneal cross-linking (CXL) treatment for keratoconus. METHODS: Interventional and comparative prospective study. Sixty-nine eyes (36 patients) suffering from keratoconus (stages 1 Amsler-Krumeich classification) were divided into four groups: sequential topography-guided photorefractive keratectomy with CXL, simultaneous topography-guided photorefractive keratectomy with CXL, simultaneous non-topography guided photorefractive keratectomy with CXL, and sequential non-topography guided photorefractive keratectomy with CXL. The main outcome measures were pre- and postoperative uncorrected distance visual acuity (UDVA), best corrected distance visual acuity (CDVA), manifest refraction, contrast sensitivity, and keratometry. RESULTS: All analyzed visual, contrast sensitivity, and refractive parameters showed a significant improvement in the four groups (all P<0.05). A noticeable improvement was seen in keratometry in all the groups, and a remarkable difference was observed between topography-guided groups in comparison to non-topography-guided groups (P<0.05). Interestingly, the improvement in all parameters showed a degree of stability to the end of the follow-up. CONCLUSION: The treatment priorities in all four groups are safety, efficacy, and predictability in the correction of the sphero-cylindrical errors in mild and moderate keratoconus. No significant differences among groups in the recorded objective outcomes were found.

Umbilical Cord Mesenchymal Stem/Stromal Cells Potential to Treat Organ Disorders; An Emerging Strategy.

Currently, Mesenchymal Stem/Stromal Cells (MSCs) have attracted growing attention in the context of cell-based therapy in regenerative medicine. Following the first successful procurement of human MSCs from Bone Marrow (BM), these cells isolation has been conducted from various origins, in particular, the Umbilical Cord (UC). Umbilical Cord-Derived Mesenchymal Stem/Stromal Cells (UC-MSCs) can be acquired by a non-invasive plan and simply cultured, and thereby signifies their superiority over MSCs derived from other sources for medical purposes. Due to their unique attributes, including self-renewal, multipotency, and accessibility concomitant with their immunosuppressive competence and lower ethical concerns, UC-MSCs therapy is described as encouraging therapeutic options in cell-based therapies. Regardless of their unique aptitude to adjust inflammatory response during tissue recovery and delivering solid milieu for tissue restoration, UC-MSCs can be differentiated into a diverse spectrum of adult cells (e.g., osteoblast, chondrocyte, type II alveolar, hepatocyte, and cardiomyocyte). Interestingly, they demonstrate a prolonged survival and longer telomeres compared with MSCs derived from other sources, suggesting that UC-MSCs are desired source to use in regenerative medicine. In the present review, we deliver a brief review of UC-MSCs isolation, expansion concomitantly with immunosuppressive activities, and try to collect and discuss recent pre-clinical and clinical researches based on the use of UC-MSCs in regenerative medicine, focusing on with special focus on in vivo researches.

Cell-based Therapy for Ocular Disorders: A Promising Frontier.

As the ocular disorders causing the long-term blindness or optical abnormalities of the ocular tissue entirely affect life quality, an insight into their corresponding pathogenesis and the expansion of attitudes authorizing earlier detection and treatment need more consideration. Though current therapeutics result in desirable outcomes, they do not offer an inclusive solution for hindrance of development of visual impairment to blindness. Accordingly, stem cells because of their particular competencies have attracted pronounced attention to be applied in regenerative medicine of ocular diseases. In the last decades, a wide spectrum of stem cells surrounding Mesenchymal Stem/Stromal Cells (MSC), Neural Stem Cells (NSCs), and embryonic/induced pluripotent stem cells (ESCs/iPSCs) accompanied by Müller glia, ciliary epithelia-derived stem cells, and Retinal Pigment Epithelial (RPE) stem cells have been widely investigated to report their safety and efficacy in preclinical models and also human subjects. In this regard and the first interventions, RPE cell suspensions were successfully utilized to ameliorate visual defects of the patients suffering from Age-related Macular Degeneration (AMD) after subretinal transplantation. Herein, we will explain the pathogenesis of ocular diseases and highlight the novel discoveries and recent findings in the context of stem cell-based therapies in these disorders, focusing on the last decade's in vivo reports.

Topical Erythropoietin for Treatment of Scleral Necrosis.

PURPOSE: To investigate the safety and efficacy of topical erythropoietin for the treatment of scleral necrosis. METHODS: This study enrolled eight consecutive patients with scleral necrosis due to previous ocular surgery, rheumatoid arthritis-associated necrotizing anterior scleritis, and thermal and chemical burns. Conventional treatments failed to heal avascular scleral lesions in all eyes. Patients were treated with topical erythropoietin (3000 IU/mL) four times a day. RESULTS: The mean patient age was 37.6 ± 15.5 years. The interval between the development of scleral necrosis and initiation of topical erythropoietin was 25.6 ± 12.0 days. The necrotic sclera completely healed within 31.9 ± 16.9 days in all patients. The avascular lesions did not recur, and there was no evidence of side effects during the study. CONCLUSION: Our results showed that topical erythropoietin could be safely used to manage scleral necrosis. Randomized clinical trials are needed to further explore the efficacy of this intervention in patients with avascular scleral lesions.

Biofabrication of chitosan/chitosan nanoparticles/polycaprolactone transparent membrane for corneal endothelial tissue engineering.

We aimed to construct a biodegradable transparent scaffold for culturing corneal endothelial cells by incorporating chitosan nanoparticles (CSNPs) into chitosan/polycaprolactone (PCL) membranes. Various ratios of CSNP/PCL were prepared in the presence of constant concentration of chitosan and the films were constructed by solvent casting method. Scaffold properties including transparency, surface wettability, FTIR, and biocompatibility were examined. SEM imaging, H&E staining, and cell count were performed to investigate the HCECs adhesion. The phenotypic maintenance of the cells during culture was investigated by flow cytometry. Transparency and surface wettability improved by increasing the CSNP/PCL ratio. The CSNP/PCL 50/25, which has the lowest WCA, showed comparable transparency with human acellular corneal stroma. The scaffold was not cytotoxic and promoted the HCECs proliferation as evaluated by MTT assay. Cell counting, flow cytometry, SEM, and H&E results showed appropriate attachment of HCECs to the scaffold which formed a compact monolayer. The developed scaffold seems to be suitable for use in corneal endothelial regeneration in terms of transparency and biocompatibility.

An In-Silico Study on the Most Effective Growth Factors in Retinal Regeneration Utilizing Tissue Engineering Concepts.

PURPOSE: Considering the significance of retinal disorders and the growing need to employ tissue engineering in this field, in-silico studies can be used to establish a cost-effective method. This in-silico study was performed to find the most effective growth factors contributing to retinal tissue engineering. METHODS: In this study, a regeneration gene database was used. All 21 protein-coding genes participating in retinal regeneration were considered as a protein-protein interaction (PPI) network via the "STRING App" in "Cytoscape 3.7.2" software. The resultant graph possessed 21 nodes as well as 37 edges. Gene ontology (GO) analysis, as well as the centrality analysis, revealed the most effective proteins in retinal regeneration. RESULTS: According to the biological processes and the role of each protein in different pathways, selecting the correct one is possible through the information that the network provides. Eye development, detection of the visible light, visual perception, photoreceptor cell differentiation, camera-type eye development, eye morphogenesis, and angiogenesis are the major biological processes in retinal regeneration. Based on the GO analysis, SHH, STAT3, FGFR1, OPN4, ITGAV, RAX, and RPE65 are effective in retinal regeneration via the biological processes. In addition, based on the centrality analysis, four proteins have the greatest influence on retinal regeneration: SHH, IGF1, STAT3, and ASCL1. CONCLUSION: With the intention of applying the most impressive growth factors in retinal engineering, it seems logical to pay attention to SHH, STAT3, and RPE65. Utilizing these proteins can lead to fabricate high efficiency engineered retina via all aforementioned biological processes.

Regression of corneal neovascularization: Adiponectin versus bevacizumab eye drops.

PURPOSE: Comparing the effect of adiponectin versus bevacizumab in decreasing corneal neovascularization. METHODS: This study was conducted on 30 eyes of 30 New Zealand Albino male rabbits. Corneal neovascularization was induced by a single 7-0 silk suture 2 mm long and 1 mm in front of the limbus for 2 weeks. Rabbits were randomly divided into three groups of adiponectin (20 µg/mL), bevacizumab (5 mg/mL) and artificial tears. The treatments continued up to 14 days. RESULTS: At the end of 14 days, the average length of vessels in rabbits treated with adiponectin, bevacizumab and control groups decreased from 2.12 ± 0.32 mm to 0.89 ± 0.46 mm (57.68% ± 19.98%) (P < 0.001), 2.30 ± 0.41 mm to 1.30 ± 0.58 mm (42.49% ± 27.17%) (P = 0.048) and from 2.12 ± 0.44 mm to 1.81 ± 0.42 mm (14.81% ± 5.64%) (P = 0.112), respectively. The length of vessels decreased 57.68% ± 19.98% and 42.49% ± 27.17% in adiponectin versus bevacizumab groups, respectively (P = 0.527). The average surface area of vessels in rabbits treated with adiponectin, bevacizumab and control groups reduced from 5.02 ± 1.50 mm2 to 1.40 ± 0.75 mm2 (70.64% ± 17.76%) (P < 0.001) 0.34 ± 1.1 mm2 to 2.80 ± 1.04 mm2 (48.24% ± 19.23%) (P = 0.039) and 5.12 ± 2.92 mm2 to 4.4 ± 2.55 mm2 (14.68% ± 4.19%) (P = 0.117). Mean surface area of vascularization decreased 70.64% ± 17.76% and 48.24% ± 19.23% in adiponectin versus bevacizumab, respectively (P = 0.013). CONCLUSIONS: The results of this study suggest that topical adiponectin can decrease recent corneal neovascularization.

A hybrid scaffold of gelatin glycosaminoglycan matrix and fibrin as a carrier of human corneal fibroblast cells.

A hybrid scaffold of gelatin-glycosaminoglycan matrix and fibrin (FGG) has been synthesized to improve the mechanical properties, degradation time and cell response of fibrin-like scaffolds. The FGG scaffold was fabricated by optimizing some properties of fibrin-only gel and gelatin-glycosaminoglycan (GG) scaffolds. Mechanical analysis of optimized fibrin-only gel showed the Young module and tensile strength of up to 72 and 121 KPa, respectively. Significantly, the nine-fold increase in the Young modulus and a seven-fold increase in tensile strength was observed when fibrin reinforced with GG scaffold. Additionally, the results demonstrated that the degradation time of fibrin was enhanced successfully up to 7 days which was much longer time compared to fibrin-only gel with 38 h of degradation time. More than 45% of FGG initial mass was preserved on day 7 in the presence of aprotinin. Human corneal fibroblast cells (HCFCs) were seeded on the FGG, fibrin-only gel and GG scaffolds for 5 days. The FGG scaffold showed excellent cell viability over 5 days, and the proliferation of HCFCs also increased significantly in comparison with fibrin-only gel and GG scaffolds. The FGG scaffold illustrates the great potential to use in which appropriate stability and mechanical properties are essential to tissue functionality.