Epithelial Healing Rate Research Articles

Topical insulin for refractory persistent corneal epithelial defects

The aim was clinical evaluation of the efficacy of topical insulin eye drops in patients with refractory persistent epithelial defects (PEDs). This prospective non-randomized investigation was conducted to examine the efficacy of insulin eye drops in treating patients with PEDs that did not respond to conventional therapy. A total of twenty-three patients were included in the study, and they were administered insulin eye drops formulated as 1 U/mL, four times a day. The rate of epithelial defect resolution and time to complete corneal re-epithelialization were considered primary outcome measures. The relative prognostic impact of initial wound size and other parameters, including age, sex, smoking, diabetes, and hypertension were also analyzed. The results showed that during follow-up (maximum 50 days), a total of 16 patients (69.6%) achieved improvement. Insulin eye drops significantly reduced the corneal wounding area in 75% of patients with small epithelial defects (5.5 mm2 or less) during 20 days. Only 61% of patients with moderate epithelial defects (5.51–16 mm2) showed a significant recovery in 20–30 days. Also, 71% of patients with a defect size greater than 16 mm2, demonstrated a significant improvement in the rate of corneal epithelial wound healing in about 50 days. In conclusion topical insulin reduces the PED area and accelerates the ocular surface epithelium wound healing.

The application of a 4D-printed chitosan-based stem cell carrier for the repair of corneal alkali burns

BackgroundCorneal alkali burns can lead to ulceration, perforation, and even corneal blindness due to epithelial defects and extensive cell necrosis, resulting in poor healing outcomes. Previous studies have found that chitosan-based in situ hydrogel loaded with limbal epithelium stem cells (LESCs) has a certain reparative effect on corneal alkali burns. However, the inconsistent pore sizes of the carriers and low cell loading rates have resulted in suboptimal repair outcomes. In this study, 4D bioprinting technology was used to prepare a chitosan-based thermosensitive gel carrier (4D-CTH) with uniform pore size and adjustable shape to improve the transfer capacity of LESCs.MethodsPrepare solutions of chitosan acetate, carboxymethyl chitosan, and β-glycerophosphate sodium at specific concentrations, and mix them in certain proportions to create a pore-size uniform scaffold using 4D bioprinting technology. Extract and culture rat LESCs (rLESCs) in vitro, perform immunofluorescence experiments to observe the positivity rate of deltaNp63 cells for cell identification. Conduct a series of experiments to validate the cell compatibility of 4D-CTH, including CCK-8 assay to assess cell toxicity, scratch assay to evaluate the effect of 4D-CTH on rLESCs migration, and Calcein-AM/PI cell staining experiment to examine the impact of 4D-CTH on rLESCs proliferation and morphology. Establish a severe alkali burn model in rat corneas, transplant rLESCs onto the injured cornea using 4D-CTH, periodically observe corneal opacity and neovascularization using a slit lamp, and evaluate epithelial healing by fluorescein sodium staining. Assess the therapeutic effect 4D-CTH-loaded rLESCs on corneal alkali burn through histological evaluation of corneal tissue paraffin sections stained with hematoxylin and eosin, as well as immunofluorescence staining of frozen sections.ResultsUsing the 4D-CTH, rLESCs were transferred to the alkali burn wounds of rats. Compared with the traditional treatment group (chitosan in situ hydrogel encapsulating rLESCs), the 4D-CTH-rLESC group had significantly higher repair efficiency of corneal injury, such as lower corneal opacity score (1.2 ± 0.4472 vs 0.4 ± 0.5477, p < 0.05) and neovascularization score (5.5 ± 1.118 vs 2.6 ± 0.9618, p < 0.01), and significantly higher corneal epithelial wound healing rate (72.09 ± 3.568% vs 86.60 ± 5.004%, p < 0.01).ConclusionIn summary, the corneas of the 4D-CTH-rLESC treatment group were similar to the normal corneas and had a complete corneal structure. These findings suggested that LESCs encapsulated by 4D-CTH significantly accelerated corneal wound healing after alkali burn and can be considered as a rapid and effective method for treating epithelial defects.Graphical abstract

Risk of Induction of Corneal Neovascularization with Topical Erythropoietin: An Animal Safety Study.

To evaluate the pro-angiogenic effect of topical erythropoietin on cornea in chemical burn-injured rabbit eyes. The corneal alkali-burn injury was induced in 10 eyes of 10 rabbits using filter paper saturated with 1.0 mol sodium hydroxide. The eyes were categorized into the treatment group (n = 5) that received topical erythropoietin (3000 IU/mL) every 8 hr for one month versus the control group (n = 5) that received normal saline every 8 hr for one month. All eyes were treated with topical ciprofloxacin every 8 hr until corneal re-epithelialization was complete. Corneal epithelial defects, stromal opacity, and neovascularization were evaluated after the injury. At the conclusion of the study, the rabbits were euthanized and their corneas were submitted to histopathological examination. Baseline characteristics including the rabbits' weight and the severity of corneal injury were comparable in two groups. Time to complete corneal re-epithelialization was 37 days in the treatment group and 45 days in the control group (P = 0.83). There was no significant difference between the groups in the rate of epithelial healing or corneal opacification. Clinical and microscopic corneal neovascularization was observed in one eye (20%) in the treatment group and two eyes (40%) in the control group (P = 0.49). Recombinant human erythropoietin administered topically did not induce vessel formation in rabbit corneas after chemical burn.

Comparison of Corneal Epithelial Wound Healing between Topical RCI001, Solcoseryl, and Polydeoxyribonucleotide in the Murine Ocular Alkali Burn Model.

To compare the corneal epithelial wound healing effects of RCI001, Solcoseryl, and polydeoxyribonucleotide (PDRN) in a rat alkali burn model. In 40 male Sprague-Dawley rats, we induced alkali burn using filter paper soaked in 0.2N sodium hydroxide. The rats were then treated with topical 0.5% RCI001, 1.0% RCI001, Solcoseryl, or PDRN twice a day for 2 weeks. Corneal epithelial integrity and epithelial healing rate were measured at day 0, 3, 5, 7, 10, and 14. Histologic and immunohistochemistry findings were also assessed. Both the 0.5% and 1.0% RCI001 groups showed significantly more epithelial healing compared to the control group at day 5, 7, 10, and 14 (each p < 0.05). No statistical difference was found between the 0.5% and 1.0% RCI001 groups. Neither the Solcoseryl nor the PDRN groups showed a significant difference from the control. RCI001 treatment resulted in significantly reduced stromal edema, and a trend towards less inflammatory cell infiltration. Topical application of RCI001 showed enhanced corneal epithelial wound healing in the murine corneal alkali burn model, presumably by suppressing inflammation. Meanwhile, Solcoseryl and PDRN did not show sufficient therapeutic effects compared to RCI001.

Phase I/II randomized, double-masked, placebo-controlled study of processed amniotic fluid drops after PRK.

To evaluate the safety and efficacy of processed amniotic fluid (pAF) used postoperatively after photorefractive keratectomy (PRK). University of Utah, Moran Eye Center, Salt Lake City, Utah. Randomized, double-masked, placebo-controlled prospective study. 61 participants were randomized to receive either placebo or pAF drops, which were instilled 4 times per day for 1 week after PRK along with routine postoperative medications. The primary outcome measure was time to full re-epithelialization in days. Secondary measures included visual acuity at 30 days and postoperative pain scores during the first week. There was no significant difference in time to re-epithelialization, with a median of 5 days for both groups. There were no difference in pain indicator scores during the first week and no difference in corneal staining scores at day 30 between the 2 groups. There were no adverse events. This pilot study evaluating the safety and efficacy of pAF as an additional postoperative topical medication for PRK demonstrated that pAF did not improve the rate of epithelial healing after PRK. pAF may be safely studied in other ocular conditions to determine its effect on epithelial healing.

Effect of PKH-26-labeled exosomes derived from bone marrow mesenchymal stem cells on corneal epithelium regeneration in diabetic mice.

It is known that bone marrow mesenchymal stem cells (BM-MSCs) could speed up the regeneration of diabetic corneal epithelium. To investigate the effect of exosomes derived from mouse BM-MSCs on corneal epithelium regeneration in diabetic mice. Diabetic mouse models were established using streptozotocin (STZ), and their central corneal epithelium was scratched under a microscope. The diabetic mice were randomly divided into three groups: the control group was injected with subconjunctival phosphate buffer saline; the exosomes group was treated with a subconjunctival injection of exosomes derived from BM-MSCs; and the BM-MSCs group was treated with a subconjunctival injection of BM-MSCs. The corneal epithelium repair rates in the three groups were compared, and the distribution of the exosomes derived from BM-MSCs labeled with PKH-26 was observed by immunofluorescence. Hematoxylin-eosin staining of the corneal tissue was observed 72 h after the treatments in the three groups. The diabetic mice were successfully established by a blood glucose level >16.7 mmol/L after 8 weeks. The corneal epithelium healing rates in experimental groups 1 and 2 were significantly higher than those of the control group at 24, 48, and 72 h (P<0.05). However, there was no significant difference in the corneal epithelial healing rate between experimental groups 1 and 2 (P>0.05). The exosomes derived from BM-MSCs were found in the superficial corneal stroma in experimental groups 1 and 2, with the majority of the exosomes distributed in the limbal epithelium at the edge of the injury area. The proliferation of corneal epithelial cells in experimental groups 1 and 2 was more obvious than that in the control group. The exosomes derived from BM-MSCs labeled with PKH-26 significantly promoted the repair of corneal epithelial injury in diabetic mice. These exosomes might be a substitute for BM-MSCs in the repair of diabetic keratopathy, suggesting a new idea for the repair of diabetic keratopathy with "cell-free" stem cell therapy, which will require a clinical study.

Comparison of transepithelial and conventional photorefractive keratectomy in myopic and myopic astigmatism patients: a randomized contralateral trial

BackgroundTo assess transepithelial photorefractive keratectomy (tPRK) in terms of corneal epithelial healing rate, postoperative pain, postoperative discomfort, and visual and refraction outcomes compared to mechanical epithelial debridement PRK (mPRK) and alcohol-assisted PRK (aaPRK).MethodsIn this double-masked, randomized clinical trial, thirty-nine patients underwent tPRK in one eye and mPRK in the fellow eye (arm A), and 33 patients underwent tPRK in one eye and aaPRK in the contralateral eye (arm B). All surgical procedures were done using the Schwind Amaris excimer laser. The area of corneal epithelial defect in all eyes was captured and analyzed using ImageJ software.ResultsMean epithelial healing time was respectively 3.74 ± 0.82 and 3.59 ± 0.79 days in tPRK versus mPRK (P = 0.21) in arm A, and 3.67 ± 0.92 and 3.67 ± 0.74 days in tPRK versus aaPRK (P = 1.00) in arm B. Accounting for the initial corneal epithelial defect area, the epithelial healing rate was faster in conventional PRK groups compared to tPRK (both P<0.001) in both arms. However, there was no significant difference in safety, efficacy, spherical equivalent refractive accuracy, or corneal haze development between tPRK and conventional PRK groups (all P > 0.05).ConclusionsAll three methods are effective in terms of visual and refractive outcomes. However, although time to complete re-epithelialization was similar with the three methods, the epithelial healing rate was faster in conventional PRK considering the initial corneal epithelial defect area, and the patients experienced less pain and discomfort in the first postoperative day.Trial registrationIRCT, IRCT20200317046804N1. Retrospectively registered 5 May 2020.

Gelatin methacryloyl hydrogel eye pad loaded with amniotic extract prevents symblepharon in rabbit eyes.

The aim was to evaluate the ability of gelatin methacryloyl (GelMA) hydrogel eye pads loaded with amniotic extract to prevent symblepharon in rabbits. Forty-eight rabbits were divided into 3 groups. After ocular alkali burn, Group A (n=16) was treated with amniotic extract-loaded hydrogel eye pads placed in the conjunctivalsac, Group B (n=16) was treated with amniotic membrane transplantation, and Group C (n=16) received no treatment. At 1, 2, 3, and 4 weeks post-injury, 4 rabbits from each group were selected to evaluate for symblepharon, determine epithelial healing rate and corneal neovascularization, conduct histopathology, and to quantify the expression of TGF-β1. At 1 week post-injury, the epithelial healing rate in Groups A and B was higher than Group C (p=0.002, 0.001, respectively). At 2 weeks, corneal neovascularization in Group B was less than Group C (p=0.004). At 3 and 4 weeks, no symblepharon has been found in Group A, but it was found in some eyes in Group B and C (p=0.009, 0.013). Further, the expression of TGF-β1 in Group A was lower than in Group B and C (p<0.001). H&E staining showed that the controls in Group C had more edema and inflammatory cell infiltration in the first 2 weeks, relative to Groups A and B. At 4 weeks, Masson's Trichrome staining showed that fibers were most regularly aligned in Group A and that immuno-histochemical staining found that proliferating cell nuclear antigen was highest expressed in Group C. Treatment with GelMA hydrogel eye pads loaded with amniotic extract shortly after chemical injury prevented symblepharon in rabbits.

Allogenic Simple Limbal Epithelial Transplantation Versus Amniotic Membrane Grafting in the Early Management of Severe-Grade Ocular Chemical Injuries—A Retrospective Comparative Study

To compare outcomes of management in the early stage of severe chemical injury (grade 4 and worse; Dua classification) with amniotic membrane grafting (AMG) alone vs allogenic simple limbal epithelial transplantation (alloSLET). Retrospective comparative interventional case series. Retrospective comparative interventional series. Records of patients with severe ocular chemical injury who underwent AMG alone (between 2009 and 2013) vs alloSLET (between 2013 and 2017) were analyzed for grade of injury, time of and interventions for epithelial healing, ocular surface status post healing (grade of symblepharon, and limbal stem cell deficiency [LSCD]), and type of and need for interventions in the chronic stage. Among patients presenting in early stage of severe chemical injury, 38 eyes (median age 11 years) managed with AMG alone were compared with 39 eyes (median age 8 years) managed with alloSLET. The mean time of presentation post injury was 33.85 ± 27.5 and 40.6 ± 23.5days in the AMG and alloSLET group, respectively. The rate of epithelial healing was faster in the alloSLET group and the difference was noted to be statistically significant (odds ratio [OR] 0.966, P= .001). Similarly, the lower occurrence of LSCD (OR 0.137, P= .004) and need for keratoplasty (OR 0.093, P= .003) favored alloSLET over AMG. Final best-corrected visual acuity of >20/200 was achieved in 39.4% and 53.8% in the AMG and alloSLET groups, respectively. AlloSLET helps in faster epithelialization of the surface, thus reducing the need for subsequent surgeries in the chronic stage and aiding faster visual rehabilitation. The outcomes of alloSLET appear superior to amniotic membrane grafting alone and should be considered in eyes with grade 4 and above (Dua classification) chemical injuries in the early stage.

Agrin Promotes Limbal Stem Cell Proliferation and Corneal Wound Healing Through Hippo-Yap Signaling Pathway.

PurposeTo investigate the effect and mechanism of Agrin on limbal stem cell proliferation and corneal wound healing.MethodsLimbal stem cells were isolated and treated with different concentrations of Agrin. CCK-8 and cell proliferation markers (Ki67 and pH3) were detected to evaluate cell numbers or proliferative potential of limbal stem cells. The corneal epithelium wound model was induced by debridement of central corneal epithelial, and the effects of Agrin on limbal stem cell proliferation and corneal epithelial wound healing rate were determined.ResultsAgrin promoted the proliferation of cultured limbal stem cells in vitro and increased the expression level of p63α rather than keratin 12. Furthermore, Agrin accelerated the wound healing rate of corneal epithelium through activating limbal stem cell proliferation in vivo. In terms of mechanism, Agrin could facilitate the dephosphorylation of Yap1, which contributed to the nuclear translocation of Yap1 and expression of Cyclin D1, and subsequently promoted proliferation of limbal stem cells.ConclusionsAgrin promotes the proliferation of limbal stem cells and accelerates the healing rate of corneal wound through Hippo-Yap signaling pathway.

The Efficacy of Topical HGF on Corneal Fibrosis and Epithelial Healing after Scar-Producing PRK Injury in Rabbits.

PurposeTo determine the effect of topical hepatocyte growth factor (HGF) on myofibroblast development and corneal opacity after fibrosis-producing photorefractive keratectomy (PRK).MethodsTwelve New Zealand rabbits had transepithelial PRK. Six rabbits received topical recombinant human HGF (rhHGF) (50 µL of 0.1 mg/mL) 3 times a day for 1 week beginning 6 hours prior surgery and until full closure of the epithelium, and 6 control rabbits received vehicle by the same schedule. Slit lamp photos were taken immediately and at 43 to 45 hours after surgery to determine the rate of epithelial healing. Slit lamp photographs and immunohistochemistry for α-smooth muscle actin were analyzed at 1 month in masked fashion.ResultsThe rhHGF group tended to have slower re-epithelization when compared with the controls, but no statistically significant difference was noted (P = 0.62). There was no significant difference in the density of myofibroblasts in the central stroma (P = 0.49) or corneal opacity (P = 0.84) between the HGF and control groups at 1 month after PRK.ConclusionsTopical rhHGF applied three times a day during the early postoperative period prior to epithelial closure did not significantly change the corneal epithelial healing rate, myofibroblast density, or opacity compared with vehicle after transepithelial −9.0 D PRK injury of the central cornea in rabbits.Translational RelevanceHGF has been reported to decrease myofibroblast generation and fibrosis in many organs, but topical HGF applied to the cornea until epithelial healing had no effect on scarring fibrosis in rabbit corneas.

The effect of human platelet lysate on corneal nerve regeneration

AimThis study aimed to test whether human platelet lysate (HPL) has neurotrophic ability for corneal nerve regeneration.MethodsWe measured the neurotrophic factors in human peripheral serum (HPS) and two commercially available...

Abstract 8: Corneal Neurotization Rescues the Corneal Epithelium from Thinning in a Rat Model of Neurotrophic Keratopathy

PURPOSE: The cornea is one of the most densely innervated tissues in the body, and in the absence of corneal sensory innervation, patients develop Neurotrophic Keratopathy (NK). NK is a disease characterized by corneal epithelial breakdown that can lead to progressive corneal scarring and ultimately, vision loss. Corneal neurotization uses nerve autografts to restore sensory innervation in the NK cornea.1,2 In our rat model of NK, we previously demonstrated that corneal neurotization with common peroneal and sural nerve grafts reduces epithelial breakdown, prevents scarring, and improves the rate of epithelial healing in the cornea3. Central corneal epithelial thinning is present in corneal denervation and NK. In the present study, we evaluate the effect of corneal neurotization on corneal epithelial and stromal thickness in a rat model of NK. METHODS: Previously validated models of NK and corneal neurotization were used in this study. The experimental groups were rats with i) NK (negative control) and ii) NK treated with corneal neurotization (treatment), and the control group consisted of rats with normally innervated corneas. In the experimental groups, NK was achieved with stereotactic ablation of the ophthalmic nerve. Four weeks after ablation, affected corneas (n=5 per group) were harvested. Three 10μm cross-sections from each cornea, sampled from representative areas of the cornea, were stained with Hematoxylin and Eosin for analysis. Each section was imaged with bright-field microscopy at 200X magnification. The epithelial and stromal thicknesses of each section were measured using ImagePro. Mean thicknesses were compared using the Kruksal-Wallis test and unpaired t-tests. RESULTS: The central epithelial thickness of the NK corneas (15.83 ± 1.62) was significantly decreased compared to that of the central epithelium in the treated (25.07 ± 3.89, p < 0.05) and normally innervated corneas (24.75 ± 2.46, p < 0.05), the treated and normally innervated corneas not being significantly different. In contrast, the stromal thicknesses were insignificantly different in all three groups. CONCLUSIONS: Corneal neurotization rescues the NK cornea from central epithelial thinning, suggesting the reinnervating axons of the inserted graft restore corneal epithelial integrity. We are pursuing further research with the same rat models of NK and corneal neurotization to elucidate the underlying mechanisms. REFERENCES: 1. Elbaz U, Bains R, Zuker RM, Borschel GH, Ali A. Restoration of corneal sensation with regional nerve transfers and nerve grafts: A new approach to a difficult problem. JAMA Ophthalmol. 2014;132(11):1289–1295. doi:10.1001/jamaophthalmol.2014.2316 2. Bains RD, Elbaz U, Zuker RM, Ali A, Borschel GH. Corneal neurotization from the supratrochlear nerve with sural nerve grafts: A minimally invasive approach. Plast Reconstr Surg. 2015;135(2):397e-400e. doi:10.1097/PRS.0000000000000994 3. Catapano J, Antonyshyn K, Zhang JJ, Gordon T, Borschel GH. Corneal neurotization improves ocular surface health in a novel rat model of neurotrophic keratopathy and corneal neurotization. Investig Opthalmology Vis Sci. 2018;59(11):4345–4354.

Use of commercially available sodium hyaluronate 0.18% eye drops for corneal epithelial healing in diabetic patients.

To evaluate the effect of topical sodium hyaluronate (SH) 0.18% treatment on corneal epithelial healing after epithelial debridement in pars plana vitrectomy in diabetic patients. This is prospective and randomized clinical trial. Our study population included 30 eyes undergoing pars plana vitrectomy that required near total corneal debridement intra-operatively for surgical view. We compared the residual wound and wound healing rate in between 3 groups: 10 diabetic eyes (DMV) on topical SH 0.18%; 10 diabetic eyes (DMC) and 10 non-diabetic eyes (NDM) not treated with topical SH 0.18%. The corneal epithelial wound was measured at 12, 24, 36, 48, 60, 72 and 120h after the vitrectomy surgery. DMC group had corneal wounds that reepithelialization significantly more slowly than in NDM and DMV groups at 12, 24, 36 and 48h (Mann-Whitney test p < 0.05). The epithelial healing rate was significantly faster at 12h in NDM and DMV group (Mann-Whitney test p < 0.05). No differences in the residual epithelial wound and wound healing were detected in between NDM and DMV groups. The mean for epithelial closure in DMC group was delayed 87.6 ± 28.31h, compared with DMV group (64.8 ± 21.31) and NDM group (56.4 ± 9.88). All groups were followed up 1month beyond completed wound closure. No recurrent corneal epithelial wound, corneal melting or corneal neovascularization was noted. Diabetic patients on SH 0.18% four times daily for epithelial defect had similar corneal wounds healing rate as non-diabetics. This treatment significantly improved corneal wound healing and accelerated complete corneal wound resurfacing in diabetic patients.

Evaluation of early postoperative ocular pain after photorefractive keratectomy and corneal crosslinking

To evaluate and compare early postoperative pain after photorefractive keratectomy (PRK) and corneal crosslinking (CXL). Khatam-al-Anbia Eye Hospital, Mashhad, Iran. Prospective case series. The PRK group included patients with simple refractive errors whereas the CXL group included patients with clinical keratoconus. The groups were compared regarding the level of pain based on the visual analogue scale (VAS), verbal rating scale (VRS), and Wong-Baker FACES pain rating scale immediately after surgery, 6hours postoperatively, and 1, 3, and 7days postoperatively. The epithelial defect size was measured at 6hours after surgery and 1day and 3days after surgery in both groups. The study comprised 68 patients (34 patients in the PRK group and 34 patients in the CXL group). The epithelial defect size was significantly smaller in the CXL group than in the PRK group (P<.001); however, the amount of pain was significantly higher after CXL than after PRK based on VAS and VRS (P=.04 and P=.019, respectively). In the FACES scaling system, the pain score was also higher in the CXL group than in the PRK group. However, the difference was not statistically significant. No intraoperative or postoperative complications were observed during follow-up. The epithelial defect healing rate was statistically significantly faster in the CXL group than in the PRK group. However, the level of pain was greater in the CXL group, suggesting that postsurgical pain might be influenced by other factors than the epithelial defect.

The Effect of Topical Substance-P Plus Insulin-like Growth Factor-1 (IGF-1) on Epithelial Healing After Photorefractive Keratectomy in Rabbits.

PurposeTo determine whether topical Substance-P (SP) plus insulin-like growth factor-1 (IGF-1) can improve corneal healing after photorefractive surface ablation in a rabbit.MethodsAfter a 9.0-mm corneal de-epithelialization using a combination of chemical (18% alcohol) and mechanical debridement, excimer photorefractive surface ablation was performed bilaterally in eight rabbits (16 eyes) with an 8.0-mm ablation zone and 70-μm depth. The right eye was treated with SP (250 μg/mL) and IGF-1 (25 ng/mL) in hyaluronic acid, one drop twice a day, and the other eye treated with only hyaluronic acid. The epithelial healing process was documented photographically twice a day until healing was complete. Six rabbits were sacrificed 6 weeks after photorefractive keratectomy (PRK) and corneas examined histologically.ResultsSeven of eight rabbit eyes treated with SP/IGF-1 healed in a shorter time than the untreated eye. For rabbit #6, both eyes healed at the same time. The average healing time (total time until wound closure) for the treated eyes was 99 hours, while the average healing time for the untreated eyes was 170 hours (P = 0.0490). A persistent epithelial defect was found in two of the nontreated eyes but none in the treated eyes. Corneal pathology showed some degree of epithelial separation in the central corneal wound in three out of six nontreated eyes and in just the treated eye of rabbit #6.ConclusionTopical SP plus IGF-1 increases the epithelial healing rate after PRK. There may have been beneficial effects upon cell adhesion as well.Translational RelevanceBetter and faster healing.

Mesenchymal Stem Cells Promote Diabetic Corneal Epithelial Wound Healing Through TSG-6–Dependent Stem Cell Activation and Macrophage Switch

To explore the role and mechanism of bone marrow-derived mesenchymal stem cells (BM-MSCs) in corneal epithelial wound healing in type 1 diabetic mice. Diabetic mice were treated with subconjunctival injections of BM-MSCs or recombinant tumor necrosis factor-α-stimulated gene/protein-6 (TSG-6). The corneal epithelial wound healing rate was examined by fluorescein staining. The mRNA and protein expression levels of TSG-6 were measured by quantitative RT-PCR and Western blot. The infiltrations of leukocytes and macrophages were analyzed by flow cytometry and immunofluoresence staining. The effect of TSG-6 was further evaluated in cultured limbal epithelial stem/progenitor cells, macrophages, and diabetic mice by short hairpin RNA (shRNA) knockdown. Local MSC transplantation significantly promoted diabetic corneal epithelial wound healing, accompanied by elevated corneal TSG-6 expression, increased corneal epithelial cell proliferation, and attenuated inflammatory response. Moreover, in cultured human limbal epithelial stem/progenitor cells, TSG-6 enhanced the colony-forming efficiency, stimulated mitogenic proliferation, and upregulated the expression level of ΔNp63. Furthermore, in diabetic mouse cornea and in vitro macrophage culture, TSG-6 alleviated leukocyte infiltration and promoted the polarization of recruited macrophages to anti-inflammatory M2 phenotypes with increased phagocytotic capacity. In addition, the promotion of epithelial stem/progenitor cell activation and macrophage polarization by MSC transplantation was largely abrogated by shRNA knockdown of TSG-6. This study provided the first evidence of TSG-6 secreted by MSCs promoting corneal epithelial wound healing in diabetic mice through activating corneal epithelial stem/progenitor cells and accelerating M2 macrophage polarization.

Evidence-Based Update on Ocular Chemical Injuries

Chemical injuries of the eye remain a serious cause of visual disability. The current literature is reviewed, with a focus on recent studies that inform evidence-based treatment decisions. Prevention continues to be a primary goal. In addition to conventional therapy (urgent irrigation, topical corticosteroids and antibiotics, oral vitamin C, possibly doxycycline and topical antioxidants), there is evidence that amniotic membrane, umbilical cord serum, or platelet-rich plasma may improve epithelial healing rates in moderate to severe burns. Reconstruction of the ocular surface continues to evolve; for unilateral disease, simple limbal epithelial transplant (SLET) is gaining momentum. For bilateral total limbal stem cell deficiency, treatment options include allogeneic keratolimbal allograft, ex vivo expansion of cultured epithelial sheets, and keratoprosthesis; each intervention represents a unique balance of risks and benefits. SLET appears to be simple and effective for unilateral limbal stem cell deficiency secondary to chemical injuries. The treatment of bilateral injuries requires additional studies to define the preferred practice patterns, as there is no clear consensus regarding the preferred intervention.

Randomized Controlled Trial of Topical Insulin for Healing Corneal Epithelial Defects Induced During Vitreoretinal Surgery in Diabetics.

To determine the effect of topical insulin of 3 concentrations [0.5, 1, and 2 units per drop 4 times per day (QID)] on postoperative corneal epithelial wound healing in diabetic patients. A double blind randomized controlled hospital-based study involving diabetic patients with postoperative corneal epithelial defect after vitreoretinal surgery. Diabetic patients were randomized to 3 different concentrations of topical insulin (DTI 0.5, DTI 1, and DTI 2) or placebo in the control group (DNS). Primary outcome measure was the rate of corneal epithelial wound healing (mm² per hour) over pre-set interval and time from baseline to minimum size of epithelial defect on fluorescein stained anterior segment digital camera photography. Secondary outcome measure was any adverse effect of topical insulin. Follow-up was 1 month. Thirty-two eyes of 32 patients undergoing intraoperative corneal debridement with resultant epithelial defect (8 eyes per group) were analyzed. DTI 0.5 was superior to other concentrations achieving 100% healing rate within 72 hours of treatment compared with 62.5% in DNS, 75% in DTI 1, and 62.5% in DTI 2. Statistically, DTI 0.5 achieved significant results (P = 0.036) compared with the diabetic control group (DNS) in terms of mean rate of corneal epithelial wound healing from maximum to minimum defect size. No adverse effect of topical insulin was reported. Topical insulin 0.5 units QID is most effective for healing corneal epithelial defect in diabetic patients after vitrectomy surgery compared with placebo and higher concentrations. Topical insulin is safe for human ocular usage.

Thrombomodulin promotes corneal epithelial wound healing.

PurposeTo determine the role of thrombomodulin (TM) in corneal epithelial wound healing, and to investigate whether recombinant TM epidermal growth factor-like domain plus serine/threonine-rich domain (rTMD23) has therapeutic potential in corneal epithelial wound healing.MethodsTM localization and expression in the murine cornea were examined by immunofluorescence staining. TM expression after injury was also studied. The effect of rTMD23 on corneal wound healing was evaluated by in vitro and in vivo assays.ResultsTM was expressed in the cornea in normal adult mice. TM expression increased in the early phase of wound healing and decreased after wound recovery. In the in vitro study, platelet-derived growth factor-BB (PDGF-BB) induced TM expression in murine corneal epithelial cells by mediating E26 transformation-specific sequence-1 (Ets-1) via the mammalian target of rapamycin (mTOR) signaling pathway. The administration of rTMD23 increased the rate of corneal epithelial wound healing.ConclusionsTM expression in corneal epithelium was modulated during the corneal wound healing process, and may be regulated by PDGF-BB. In addition, rTMD23 has therapeutic potential in corneal injury.