0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial.

We determined the efficacy and safety of 0.1% RGN-259 ophthalmic solution (containing the regenerative protein thymosin ß4) in promoting the healing of persistent epithelial defects in patients with Stages 2 and 3 neurotrophic keratopathy. Complete healing occurred after 4 weeks in 6 of the 10 RGN-259-treated subjects and in 1 of the 8 placebo-treated subjects (p = 0.0656), indicating a strong efficacy trend. Additional efficacy was seen in the significant healing (p = 0.0359) with no recurrent defects observed at day 43, two weeks after cessation of treatment, while the one healed placebo-treated subject at day 28 suffered a recurrence at day 43. The Mackie classification disease stage improved in the RGN-259-treated group at Days 29, 36, and 43 (p = 0.0818, 0.0625, and 0.0467, respectively). Time to complete healing also showed a trend towards efficacy (p = 0.0829, Kaplan-Meier) with 0.1% RGN-259. RGN-259-treated subjects had significant improvements at multiple time points in ocular discomfort, foreign body sensation, and dryness which were not seen in the placebo group. No significant adverse effects were observed. In summary, the use of 0.1% RGN-259 promotes rapid healing of epithelial defects in neurotrophic keratopathy, improves ocular comfort, and is safe for treating this challenging population of patients.

Hyaluronic Acid-Pluronic®F127-Laden Soft Contact Lenses for Corneal Epithelial Healing: In Vitro and In Vivo Studies.

Hyaluronic acid (HA) is widely used to treat various ocular diseases like dry eye syndrome, keratoconus, and other corneal epithelial injuries. The currently available eye drop solutions need frequent doses affecting the routine life style of patients. In this work, the silicone contact lens was designed to entrap HA and Pluronic®F127 to improve the wettability of the contact lens to treat various ocular diseases. The soaking method (HA-SM) was compared with the direct entrapment (DL-HA-PI) technique. The HA-Pluronic®F127-laden contact lenses (DL-HA-PI) showed acceptable optical transmittance with improved swelling (water content) properties. The in vitro release data showed high burst release with HA-SM contact lenses (12-36 h), while DL-HA-PI contact lenses showed prolong release up to 96 h. The in vivo release in the rabbit tear fluid showed high HA concentration (tear fluid) with DL-HA-PI contact lenses in comparison to the HA-SM contact lenses. The DL-HA-PI-3 batch with Pluronic®F127 showed more promising results in schirmer strip study in comparison to DL-HA-3 batch (without Pluronic®F127). The presence of Pluronic®F127 with HA showed high potential to improve hydration property of the contact lens. The corneal healing model showed reduction in the ocular inflammatory symptoms with DL-HA-PI-3 batch, thus demonstrating the potential of HA and Pluronic®F127 to be used in various ocular diseases.

Comparison of growth factor and interleukin content of adult peripheral blood and cord blood serum eye drops for cornea and ocular surface diseases.

INTRODUCTION: Various blood-derived products have been proposed for the topical treatment of ocular surface diseases. The aim of the study was to compare the different content of Growth Factors (GFs) and Interleukins (ILs) in peripheral blood (PB-S) and Cord Blood (CB-S) sera. MATERIALS AND METHODS: Sera were obtained from 105 healthy adult donors (PB-S) and 107 umbilical/placental veins at the time of delivery (CB-S). The levels of epithelial-GF (EGF), fibroblast-GF (FGF), platelet-derived-GF (PDGF), insulin-GF (IGF), transforming-GF alpha (TGF-α,) and beta 1-2-3 (TGF-ß1-ß2-ß3), vascular endothelial-GF (VEGF), nerve-GF (NGF), Interleukin (IL)-1ß,IL-4,IL-6,IL-10, and IL-13 were assessed by Bio-Plex Protein Array System (Bio-Rad Laboratories, CA, USA). The Mann-Whitney test for unpaired data was applied to compare GFs and ILs levels in the two sources. The associations among each GF/IL level and the obstetric data for CB-S and hematological characteristics for PB-S were also investigated. RESULTS: The levels of EGF, TGF-α, TGF-ß2, FGF, PDGF, VEGF, NGF, IL-1B, IL-4, IL-6, IL-10, and IL-13 were significantly higher in CB-S compared to PB-S. Conversely, the levels of IGF-1, IGF-2, and TGF-ß1 were significantly higher in PB-S. The female sex and the weight of the child showed a significant association in predicting EGF and PDGF levels. CONCLUSION: A significantly different content in those GFs and ILs was demonstrated in the two blood sources. Since each GF/IL selectively regulates different cellular processes involved in corneal healing, the use of PB-S or CB-S should be chosen on the basis of the cellular mechanism to be promoted in each clinical case.

Medicated ocular bandages and corneal health: potential excipients and active pharmaceutical ingredients.

Corneal blindness can occur due to improper healing of the corneal tissues after induced injury or abrasion which can be accidental, pathogenic, or after corneal surgery. Abnormal regulation of the healing mechanisms can lead to corneal opacity. Reducing inflammation and promoting epithelial wound healing are crucial for scar-free corneal recovery without eyesight complications. Current approaches for corneal wound healing involve amniotic membrane (AM) bandages, bandage contact lenses (BCL), and collagen shields in conjunction with frequent administration of therapeutic eye drops. The problem with eye drops is poor bioavailability and patient incompliance that might lead to corneal wound healing complications and poor clinical outcomes. Various methods have been proposed for loading drugs into medicated bandage lenses. There are advantages and limitations associated with each technique regarding the ease of manufacture, drug loading, release kinetics, and suitability with various therapeutics and hydrogel types. There is still, however, no drug-eluting corneal bandage on the market despite the need for such a convenient and cost-efficient strategy for corneal wound healing. This review will highlight materials and therapeutics that can be used in medicated ocular bandages and various ways of incorporating drugs, while discussing the limitations and challenges associated with bringing medicated ocular bandages in the market.

Short-term effects of extremely low-frequency pulsed electromagnetic field and pulsed low-level laser therapy on rabbit model of corneal alkali burn.

This study was conducted to investigate the effect of combining extremely low frequency-pulsed electromagnetic field (ELF-PEMF) and low-level laser therapy (LLLT) on alkali-burned rabbit corneas. Fifty alkali-burned corneas of 50 rabbits were categorized into five groups: ELF-PEMF therapy with 2 mT intensity (ELF 2) for 2 h daily; LLLT for 30 min twice daily; combined ELF-PEMF and LLLT (ELF + LLLT); medical therapy (MT); and control (i.e., no treatment). Clinical examination and digital photography of the corneas were performed on days 0, 2, 7, and 14. After euthanizing the rabbits, the affected eyes were evaluated by histopathology. The clinical and histopathologic results were compared between the groups. On days 7 and 14, no significant difference in the corneal defect area was evident between the ELF, LLLT, ELF + LLLT, and MT groups. Excluding the controls, none of the study groups demonstrated a significant corneal neovascularization in both routine histopathology and immunohistochemistry for CD31. Keratocyte loss was significantly higher in the MT group than in the ELF, LLLT, and ELF + LLLT groups. Moderate to severe stromal inflammation in the LLLT group was comparable with that in the MT group and was significantly lower than that in the other groups. In conclusion, combining LLLT and ELF was not superior to ELF alone or LLLT alone in healing corneal alkali burns. However, given the lower intensity of corneal inflammation and the lower rate of keratocytes loss with LLLT, this treatment may be superior to other proposed treatment modalities for healing alkali-burned corneas.

Safety and Effectiveness of Topical Anesthetics in Corneal Abrasions: Systematic Review and Meta-Analysis.

BACKGROUND: Topical anesthetics are used in the emergency department (ED) to relieve eye pain and allow eye examinations in patients with corneal abrasions. There is concern for delayed corneal healing, which is associated with the long-term use of topical anesthetics, so outpatient use is not recommended. OBJECTIVES: We sought to systematically study the effectiveness and complications associated with the short-term use of topical anesthetics (≤72 hours) in the management of patients presenting to EDs with corneal abrasions. METHODS: Four electronic databases were searched from inception of the database until April 2014. We included studies of patients >16 years of age who were using topical anesthetics for <72 hours. Postoperative cases were not included. RESULTS: A total of 140 patients (68 in the intervention group and 72 in the control group) from 2 randomized trials were included in the analysis. Comparing control patients who did not use topical anesthetics to study patients who did use topical anesthetics, this meta-analysis found no significant difference in pain scores (standardized mean difference -1.01 [95% confidence interval {CI} -2.39 to 0.38), corneal healing (OR 1.31 [95% CI 0.53-3.27), or persistent symptoms (OR 0.98 [95% CI 0.06-16.69). The 2 trials reported no adverse effects. CONCLUSION: There were no differences regarding pain, persistent symptoms, or corneal healing when comparing short-term use of topical anesthetics to placebo in the treatment of corneal abrasion. Data on safety are sparse, and the use of this treatment is currently not supported by evidence.

Investigation of topical amniotic membrane suspension and ReGeneraTing Agent on early corneal stromal healing in rats.

Innovative topical bioregenerative materials promoting corneal stromal healing provide valuable alternatives for treating patients with deep corneal ulcers, and particularly beneficial for those with a higher anaesthetic risk. This study aimed to investigate the effects of topical amniotic membrane suspension (AMS) and ReGeneraTing Agent (RGTA) on surgically induced deep stromal ulcers in rats. Eighteen Sprague-Dawley rats were divided into 3 treatment groups: control group (topical normal saline, TID); AMS group (topical AMS, TID); RGTA group (topical RGTA, Q2D). Corneal microsurgery was used to create deep stromal ulcer. Evaluations were performed by corneal opacity grading, spectral domain optical coherence tomography (SD-OCT), histopathology, and immunohistochemistry. One-way ANOVA and Dunnett's test were used for statistical analysis. By the seventh day of treatment, both the AMS and RGTA groups showed significantly greater thickness in corneal stroma (both p-value < 0.05) than the control group. Additionally, the RGTA group exhibited a significantly higher degree of myofibroblast infiltration in the stroma and a greater level of corneal opacity (p < 0.05). No significant differences in the count of inflammatory cells were noted. In conclusion, both AMS and RGTA have demonstrated effectiveness in promoting the early stages of stromal wound healing and wound defect recovery in our research. Both AMS and RGTA have good potential for treating deep corneal ulcers in small animals practice. Further research is necessary to investigate the long-term effects and mechanism of using topical AMS and RGTA on treating deep corneal ulcer in clinical practice.

Evaluation of Moringa Oleifera Leaf Extract for its In vitro Antibacterial Properties, Mechanism of Action, and In vivo Corneal Ulcer Healing Effects in Rabbits' Eyes.

M. oleifera is the most adapted tree species in different medicinal eco-systems and has resilience against climate changes. This multiple-use tree provides healthy foods, snacks, honey, and fuel. Besides this, it has immense promising applicationsby offering antimicrobial and antibacterial activities for targeted uses. This validates the court of Hippocrates that let food be the medicine and medicine be the food for which moringa qualifies. In view of this, the antioxidant and in vitro antibacterial potency of the hydro-ethanolic extract of M. oleifera was evaluated on clinically isolated multidrug-resistant strains of Staphylococcus aureus. Furthermore, in vivo, the healing response of M. oleifera extract was analysed on corneal ulcers induced in rabbit eyes infected with methicillin-resistant Staphylococcus aureus. TheM. oleifera extract exhibited exponential antioxidant activity. In-vitro antibacterial activity was evaluated by agar well diffusion assay showing zone of inhibition ranging from 11.05±0.36 to 20±0.40 mm at concentrations of 20, 40, 80, and 160 mg/ml, whereas, in our finding, no zone of inhibition was observed below 20 mg/ml concentration, which indicated that there is threshold limit below which the antibacterial activity of M. oleifera extract is not observed. Furthermore, continuous application of 3% and 5% M. oleifera extract (eye drop) four times a day for 14 consecutive days showed a significant healing response of the eyes of rabbits with corneal ulcers. These results suggest that M. oleifera extract could be a viable alternative to existing antibacterial therapies for corneal ulcers. Additionally, there is a possibility of commercial formulation of M. oleifera extract in the form of deliverable pharmaceutical products; therefore, it should be explored further.

Impact of Latent Virus Infection in the Cornea on Corneal Healing after Small Incision Lenticule Extraction.

The aim of the present study is to analyze the impact of cornea virus latent infection on corneal healing after small incision lenticule extraction (SMILE) and predict the positive rate of virus latent infection in corneal stroma. A total of 279 patients who underwent SMILE were included in this study. Fluorescence quantitative PCR was used to detect virus infection in the lenticules, which were taken from the corneal stroma during SMILE. Herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were detected. Postoperative visual acuity, spherical equivalent, intraocular pressure, corneal curvature (Kf and Ks), corneal transparency, and corneal staining were compared between the virus-positive group and the virus-negative group. The number of corneal stromal cells and inflammatory cells, corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal total branch density (CTBD), and corneal nerve fiber width (CNFW) were evaluated using an in vivo confocal microscope. Out of 240 herpes simplex virus (HSV) tested samples, 11 (4.58%) were positive, among which 5 (2.08%) were HSV-1-positive and 6 (2.50%) were HSV-2-positive. None of the 91 CMV- and EBV-tested samples were positive. There was no statistical significance in the postoperative visual acuity, spherical equivalent, intraocular pressure, Kf and Ks, corneal transparency, corneal staining, the number of corneal stromal cells and inflammatory cells, CNFD, CNBD, CNFL, CTBD, and CNFW between the virus-positive and virus-negative groups (p > 0.05). In conclusion, there is a certain proportion of latent HSV infection in the myopia population. Femtosecond lasers are less likely to activate a latent infection of HSV in the cornea. The latent infection of HSV has no significant impact on corneal healing after SMILE.

Ciclosporin A Cationic Emulsion 0.1% for the Management of Dry Eye Disease: Facts That Matter for Eye-Care Providers.

Dry eye disease (DED) is a chronic inflammatory disease of the ocular surface requiring long-term therapy. Severe forms of DED generally do not respond to tear substitutes alone or combined, and often require treatment with topical anti-inflammatory agents to break the vicious circle of inflammation. This review summarises data from randomised controlled trials and real-world evidence on the efficacy and safety of ciclosporin A 0.1% cationic emulsion (Ikervis®) for the management of DED. Improvements in clinical signs and symptoms were reported from as early as 4 weeks after treatment initiation, although it can take a few months to reach the full benefits. Treatment periods of up to 12 months provide sustained benefit to patients. In the most responsive patients, treatment discontinuation is possible with no further substantial relapse over 12 months in over 65% of patients. Transient local ocular effects are the most commonly reported adverse events.

Impact of Latanoprost Antiglaucoma Eyedrops and Their Excipients on Toxicity and Healing Characteristics in the Ex Vivo Eye Irritation Test System.

INTRODUCTION: Corneal epithelial toxicity and delayed healing process have already been attributed to preservatives or some excipients. We study the effects of galenic components in antiglaucoma drugs such as benzalkonium chloride (BAC) or surfactants like macrogolglycerol hydroxystearate 40 (MGHS 40) on corneal toxicity in an ex vivo system mimicking chronic use. METHODS: Latanoprost-containing eyedrops are available with and without preservatives on the market. Unpreserved, they are available in different formulations with various excipients like MGHS at different concentrations (0%, 2.5%, and 5%). We studied these in the ex vivo bioreactor (EVEIT) on initially injured rabbit corneas. The drugs were applied six times daily for observation periods of 3 or 5 days. BAC, 5% MGHS 40 solution, and 0.18% hyaluronic acid served as controls. Macroscopic photographic, biochemical methods and corneal integrity quantification were used for evaluation. Toxicity was assessed by measuring wound healing and corneal fluorescein sodium permeability and was confirmed by histology studies. RESULTS: The BAC-preserved formulation resulted in high corneal toxicity, which was expected. Interestingly, the preservative-free (PF) formulation containing 5% MGHS 40, carbomer, macrogol 4000, and sorbitol showed the highest corneal toxicity, followed by the control formulation with equal MGHS 40 concentration, which presented significantly less damage. No toxicity was shown by eyedrops containing 2.5% MGHS 40 or salts only. CONCLUSION: Our study demonstrates a significant corneal toxicity of certain formulations of PF antiglaucoma ophthalmic drugs containing 5% MGHS 40 with other excipients compared to other formulations with lower MGHS 40 concentrations (2.5% or 0%), or even compared to the solution containing 5% MGHS alone. This suggests a concentration-dependent toxicity of MGHS 40, especially in interaction with other excipients, which may increase its epithelial toxicity, and that has to be considered in clinical glaucoma therapy. Further single-component formulation trials are needed to support this interpretation.

High fat diet induced gut dysbiosis alters corneal epithelial injury response in mice.

PURPOSE: Commensal microbiome secretes various metabolites that can exert important effects on the host immunity and inflammation and can alter cellular functions. However, little is known regarding the effect of microbiome on corneal immunity and genetic expression. The purpose of this study is to describe the effect of diet-induced gut dysbiosis on corneal immunity and corneal gene expression after wounding. METHODS: This study is approved by the Animal Care and Use of the University of Illinois. Six-week-old female C57BL6 mice were fed on a normal chow diet (ND), isocaloric low-fat control diet (LFD), or a 21% milk high-fat diet (HFD) for six weeks. 2 mm corneal epithelial debridement was performed (n = 10). Fecal samples from mice were used for microbial diversity analysis (n > 3). Immunofluorescence staining of corneal wholemount tissue post-debridement was used to visualize immune cell distribution. RNA Seq was performed on tissue samples from corneas following debridement. RESULTS: Mice fed differing diets had significant alterations in gut microbial diversities. After corneal debridement, HFD mice experienced delayed wound healing in comparison to LFD mice and ND mice groups. However, fecal transplantation led to normalization of wound closure rates. Increased γδTCR staining was observed in the LFD group, and decreased LY6G was observed in HFD group (p < 0.05). Gene Ontology terms of differentially expressed genes included response to external stimulus, cell proliferation, migration, adhesion, defense response and leukocyte migration. Top over-represented pathways included ECM-receptor interaction, Cytokine-cytokine receptor interaction, Focal adhesion and Leukocyte trans-endothelial migration. CONCLUSIONS: Gut microbial dysbiosis alters corneal immune cell distribution, corneal response to injury, and genes related to epithelial function and corneal immunity.

Clinical and instrumental assessment of the corneal healing in moderate and severe neurotrophic keratopathy treated with rh-NGF (Cenegermin).

PURPOSE: To evaluate corneal healing in patients with moderate and severe neurotrophic keratitis (NK) treated with topical rh-NFG (Cenegermin). METHODS: Twenty-one patients (12F and 9M) aged from 21 to 93 years (62.5 ± 19.4) with moderate and severe NK were enrolled in the study. The patients were divided into 2 groups accordingly to the severity of the disease. The underlying causes of NK were determined. The VAS questionnaire was dispensed. The ocular examination comprised slit lamp evaluation, ocular surface assessment with Keratograph 5M (Oculus, Germany), corneal sensitivity with Cochet-Bonnet esthesiometer (Lunneaux, France) and corneal thickness measurement with AC-OCT (DRI, Triton, Topcon, Japan). The drops of Cenegermin 0.002% were administrated 6 times daily for 8 weeks. All participants were evaluated at baseline, after 4 and 8 weeks of the treatment. The area of corneal defect with maximum diameter less than 0.5 mm was considered as healed. The main outcome measures were corneal healing, corneal sensitivity recovery and corneal thickness in the ulcer group. RESULTS: The herpetic keratitis was the most common cause of NK. Thirteen eyes were affected by severe grade of NK with corneal ulcer and 8 eyes presented a moderate grade. After 8 weeks a complete healing of the corneal defects was registered both in moderate and severe NK. Significant increase of the corneal sensitivity and thickness were registered. CONCLUSIONS: The rh-NGF (Cenegermin) resulted effective in the treatment of the severe and moderate NK with significant recovery of the corneal sensitivity and healing of the corneal defects in both groups.

Comparative study of healing time of canine non-infectious deep ulcerative keratitis between medical therapy alone and combined treatment with medical therapy and a nictitating membrane flap: A retrospective study.

Background: Canine non-infectious deep ulcerative keratitis is considered a severe ocular disorder that possibly can progress to perforation. Immediate treatment should be directed to stimulate corneal wound healing, control infection, and minimize self-trauma while eliminating the underlying causes. Aim: This retrospective study was aimed to compare the difference in non-infectious deep corneal wound healing time between cases treated with medical therapy alone and those treated with medical therapy combined with a nictitating membrane flap. Methods: The medical records at the Ophthalmology Clinic, Small Animal Teaching Hospital, Faculty of Veterinary Science, Chulalongkorn University between January 2018 and March 2020 were retrospectively reviewed. Sixty-six eyes (from 65 dogs) diagnosed with non-infectious deep ulcerative keratitis from the medical treatment group (n = 34) and the combined treatment group (n = 32) were included. The combined treatment group was prescribed the same conservative medical administrations plus a surgical nictitating membrane flap for 14 days. Results: Healing time was defined as the duration of time from the day that the dog had been diagnosed with deep ulcerative keratitis by a fluorescein staining test to the day that the corneal fluorescein stain was negative. Overall, the mean age of dogs with deep ulcerative keratitis was 10.49 ± 4.7 years. The disease was commonly evident in females more than males. Shih Tzu was the most prevalent dog breed. The corneal healing time between dogs receiving medical therapy alone and those receiving combined treatment was not statistically significant (p = 0.386). Healing times were not significantly different between sex and breed (p = 0.41). The median corneal healing time for dogs older than 10 years in the combined treatments group (29.5 days; ranging from 20 to 46 days) was longer than for those receiving medical therapy alone (21 days; ranging from 9.5 to 30.5 days). Conclusion: Supportive therapy including a nictitating membrane flap is suggested in dogs prone to deep corneal ulcers not involving infection. Even though the healing time is not statistically significant, a nictitating membrane flap acts as a tissue bandage to reduce friction over the cornea, and it also alleviates the healing process by moistening the ocular surface.

New Devitalized Freeze-Dried Human Umbilical Cord Amniotic Membrane as an Innovative Treatment of Ocular Surface Defects: Preclinical Results.

A preclinical study was performed to investigate the efficacy and safety of a new viral inactivated, devitalized, freeze-dried and gamma-sterilized human umbilical cord amniotic membrane (lhUC-AM) for the treatment of deep scleral and corneal defects with or without perforation. Firstly, lhUC-AM was investigated on experimental deep sclerectomy in rabbit eyes (n = 12) and compared to autograft (n = 4) on cross section histology. Secondly, lhUC-AM was studied on a selected series of uncontrolled cases of corneal defects (n = 18) with or without perforation, in dogs and cats. lhUC-AM tolerance, reconstruction of the deep corneal lesion and recovery of the structural aspect of the tissue were followed post-surgery. In experimental deep sclerectomy, histology showed that the lhUC-AM was well tolerated and degraded completely in 45 days while allowing an overall quality and kinetic of scleral regeneration, similar to autograft. In the clinical situations, lhUC-AM was well tolerated, with ocular inflammatory signs quickly decreasing after surgery. Mean follow-up was 16.40 ± 11.43 months. In 15 out of 18 cases, lhUC-AM allowed ocular surface wound healing. The ocular surface was fully reconstructed three months after surgery. This study suggests a good safety and efficacy profile of lhUC-AM in the treatment of deep corneal or scleral defect in animals. This new tissue should now facilitate the treatment of severe ocular surface diseases in humans.

The Role of Hi-Tech Devices in Assessment of Corneal Healing in Patients with Neurotrophic Keratopathy.

To prove the role of high-tech investigation in monitoring corneal morphological changes in patients with neurotrophic keratopathy (NK) using Keratograph 5M (K5M) and anterior segment OCT (AS-OCT), corneal healing was monitored with Keratograph 5M (Oculus, Wetzlar, Germany) and AS-OCT (DRI, Triton, Topcon, Tokyo, Japan) in 13 patients (8F and 5M), aged from 24 to 93 years (67.8 ± 19) with severe NK, who were treated with Cenegermin 0.002% (20 µg/mL) (Oxervate®, Dompè, Farmaceutici Spa, Milan, Italy). The surface defects were evaluated on Keratograph 5M with ImageJ software and the corneal thickness variations were measured using DRI-Triton OCT software. Instrumental procedures were performed at baseline, and after 4 and 8 weeks of the treatment, respectively. The main outcome measures were reduction of the ulcers' area and corneal thickness recovery. The mean area of the corneal ulcers was reduced between baseline and 4 weeks examination in all patients, and at 8 weeks all ulcers were completely healed. An increase of the corneal thickness was evidenced between the baseline visit and after the 4- and 8-week follow-up, respectively. Additionally, only in collaborating subjects the In Vivo Confocal Microscopy (IVCM) was performed with HRT Rostock Cornea Module (Heidelberg Eng GmbH) to study the corneal nerves fibres. High-tech diagnostics with K5M, AS-OCT and IVCM proved useful in the assessment of corneal morphology and the healing process in patients with NK and could be extended to assess other corneal pathologies.

Hyaluronic acid and graphene oxide loaded silicon contact lens for corneal epithelial healing.

Hyaluronic acid (HA) eye drop solution is widely used to treat and manage various corneal diseases like keratoconus (after corneal cross-linking) and dry eye syndrome. However, ocular dosage forms like eye drop solution affect the routine life style of patients due to frequent dosing schedule. In this study, HA and reduced graphene oxide (rGO) was directly loaded in the silicon contact lenses (HA-GO-DL) and compared with the conventional soaking method (HA-GO-SM). The contact lenses at lower level of rGO showed permissible swelling and transmittance properties. The water retention property of HA-GO-DL contact lenses was confirmed by water evaporation studies. The flux data of HA-GO-SM contact lenses showed high burst release with 24 h release duration. While, HA-GO-DL lenses confirmed low burst with sustained release up to 96 h. In ocular irritation study, the HA-GO-DL-2 lenses was found to be safe. The HA-GO-DL-2 batch showed high HA-tear fluid concentration (rabbit model) and improvement in the rabbit tear fluid volume (Schirmer strip studies) in comparison to the soaking method (HA-GO-SM-2) and eye drop solution. The study successfully demonstrate the potential of HA-GO loaded contact lenses to improve tear fluid volume to manage various ocular diseases like dry eye syndrome.

Corneal haze post photorefractive keratectomy.

Corneal haze represents subepithelial corneal fibrosis, a manifestation of a pathological healing process. It occurs as a result of an epithelial-stromal lesion involving a break in the epithelial barrier. It is an inflammatory response that involves the migration, multiplication and differentiation of keratocytes into mature myofibroblasts, causing loss of corneal transparency. Although it is a transient phenomenon, this complication is feared following refractive photokeratectomy (PRK), because it can cause alterations in the quality of vision, refractive regression and decreased visual acuity. The severity of these symptoms is correlated with the severity of the corneal haze, which can be assessed clinically or by objective means such as corneal densitometry measurement. The frequency and severity of corneal haze increase with the depth of photoablation in PRK and are therefore increased during the treatment of severe ametropia. Considering that no consensus exists, the application of mitomycin C (MMC) intraoperatively and topical corticosteroids postoperatively are conventionally used to inhibit collagen synthesis, sometimes in combination with various protocols depending on the center or surgeon. This review of the literature reports the current knowledge on corneal haze, in order to better understand it and optimise its prevention in the context of a decreased MMC supply, which has occurred in the past and could recur in the future.

The proteolytic fraction from Vasconcellea cundinamarcensis accelerates wound healing after corneal chemical burn in rabbits.

INTRODUCTION: Chemical ocular burns are among the most frequently eye-related injuries, which require immediate and intensive evaluation and care since they may lead to potential complications such as superinfection, corneal perforation, and blindness.Vasconcellea cundinamarcensis, a species from Caricaceae family, contains highly active proteolytic enzymes in its latex that show healing activity in animal models bearing lesions of different etiologies. METHODS: We evaluate the ocular toxicity of the proteolytic fraction from V. cundinamarcensis (P1G10) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Hen's Egg Test-Chorioallantoic Membrane test. The corneal healing property of P1G10 was studied by the ethanol-chemical burn in the rabbit's eyes. RESULTS: P1G10 is safe for ocular administration, except when administrated at 10µg/mL. P1G10 at 1µg/mL accelerates the corneal re-epithelization achieving complete wound closure after 72h of chemical burn. Also, P1G10 modulated the inflammatory response and controlled the arrangement of collagen fibers in the stroma, demonstrating its potential corneal healing properties. CONCLUSIONS: Our work was the first one to evaluate the ophthalmic application of P1G10. Here we demonstrated that P1G10 is suitable for ocular administration and it has a promising corneal healing activity which may emerge as a new pharmacological tool to the development of a new drug for ocular surface chemical injuries in the future.

Comparative evaluation of decellularized bovine omentum alone and in combination with mitomycin-C in the management of corneal injuries in dogs.

BACKGROUND AND AIM: Ulcerative corneal lesions are common ocular affections encountered in veterinary ophthalmology, having a higher incidence in dogs with brachycephalic conformation. Prompt and effective diagnosis and repair are necessary to avoid corneal perforation and restore vision. Corneal wound healing is a complex phenomenon often resulting in vision impairment as a consequence of corneal fibrosis and pigmentation. The present study investigated the efficacy of decellularized and gamma-irradiated bovine omentum as an extracellular matrix scaffold in the reconstruction of extensive and full-thickness corneal defects, and the cytotoxic effects of mitomycin-C (MMC) to prevent corneal fibrosis and pigmentation. MATERIALS AND METHODS: Twelve injured corneas of eleven dogs irrespective of breed, age, and sex were randomly divided into Groups I and II, consisting of six corneas each. Under general anesthesia, corneal grafting with decellularized and gamma-irradiated bovine omentum was carried out in Group I, whereas Group II corneas underwent single time intra-operative application of topical MMC for 2 min before corneal grafting with the same material. Epithelialization of cornea and observations including corneal edema, neovascularization, the extent of pigmentation, corneal clarity, and scarring was recorded on days 7, 14, 21, and 60 postoperatively. RESULTS: All corneas in Group I showed early epithelialization by day 7 compared to Group II where the MMC delayed epithelialization in 50% of the corneas. Visual function scores improved greatly from 0.17±0.17 in Group II on the day of presentation to 1.0±00 by the end of the observation period compared to Group I (from 0.33±0.15 to 0.88±0.11). Although epithelialization and corneal healing were delayed, 50% of the corneas recovered with undetectable corneal scar and melanosis at the end of the observation period in Group II due to the anti-fibrotic effect of MMC. CONCLUSION: From the present study, it was concluded that re-epithelialization of the cornea was enhanced by corneal grafting with decellularized bovine omentum, and application of MMC was effective in delaying corneal fibrosis and pigmentation.