Various etiologies, including diabetic keratopathy (DK), dry eye disease (DED), and neurotrophic keratopathy (NK), can disrupt corneal homeostasis, exacerbating corneal epithelial defects. Topical insulin has emerged as a promising therapy for promoting corneal wound healing and addressing underlying pathologies. This review systematically evaluates the efficacy of topical insulin across different corneal disorders. A literature review was conducted across the PubMed, Google Scholar, and Scopus research databases. The search resulted in a total of 19 articles, consisting of clinical trials, retrospective studies, and case reports. In DK, topical insulin accelerates corneal wound healing post-vitreoretinal surgery with lower concentrations showing higher outcomes when compared to conventional therapy, possibly due to improved epithelial stem cell migration. In comparison, the dry-eye disease results are inconclusive regarding patient-reported outcomes and corneal staining. For NK, topical insulin accelerates corneal wound healing and restores corneal nerve sensation. Other persistent epithelial defect (PED) etiologies that have been treated with topical insulin are infection, immune-mediated, mechanical and chemical trauma, and chronic ocular surface alterations. Although individual mechanisms for the benefits of topical insulin for each of these etiologies have not been studied, the literature demonstrates that topical insulin is efficacious for PEDs regardless of etiology. Future clinical trials need to be conducted to further evaluate optimal dosing, duration, and use of topical insulin for the restoration of the corneal surface.

BACKGROUND: Cenegermin is approved for treatment of neurotrophic keratopathy (NK) and has been studied in patients with stage 2 or 3 NK. This study evaluated the efficacy and safety of cenegermin in adults with stage 1 NK.
METHODS: This was a phase IV, multicenter, prospective, open-label, uncontrolled trial. Adults with stage 1 NK (Mackie criteria) and decreased corneal sensitivity (≤ 4 cm) received 1 drop of cenegermin 20 mcg/ml in the affected eye(s) 6 times/day for 8 weeks with a 24-week follow-up.
RESULTS: Of 37 patients, corneal epithelial healing was observed in 84.8% (95% confidence interval [CI] 68.1-94.9%; P < 0.001) at week 8; 95.2% (95% CI 76.2-99.9%; P < 0.001) of those patients remained healed at the end of the 24-week follow-up (week 32). At week 8, 91.2% (95% CI 76.3-98.1%; P < 0.001) of patients experienced improved corneal sensitivity; this improvement was observed in 82.1% (95% CI 63.1-93.9%; P < 0.001) of patients at week 32. Mean best-corrected distance visual acuity change from baseline at week 8 was - 0.10 logMAR (standard deviation [SD], 0.15; 95% CI - 0.16 to - 0.05; P < 0.001) and at week 32 was - 0.05 logMAR (SD, 0.16; 95% CI - 0.11 to 0.01; P = 0.122). At weeks 8 and 32, 15.2% (95% CI 5.1-31.9%; P < 0.001) and 10.7% (95% CI 2.3-28.2%; P < 0.001) of patients, respectively, had a 15-letter gain from baseline. At least one adverse event (AE) was reported by 73.0% and 45.7% of patients during the treatment and follow-up periods, respectively. The most common treatment-related, treatment-emergent AEs were eye pain (37.8%), blurred vision (10.8%), and eyelid pain (8.1%); these were mostly mild or moderate and were only reported during the treatment period.
CONCLUSIONS: These results support the potential use of cenegermin for treating patients with stage 1 NK, and future confirmatory studies would be beneficial to elaborate on these findings.
BACKGROUND: DEFENDO; NCT04485546.

Increased intraocular pressure (IOP) is a risk factor for glaucoma. One treatment option is trabeculectomy. Antimetabolic agents are used in the operation to decrease the post-operative scarring of the wound. The two most common medicines are Mitomycin C (MMC) and 5-Fluorouracil (5-FU). The aim of this research is to assess the effect of MMC on post-operation wound healing in comparison with 5-FU in addition to trabeculectomy. Well, we went through four common databases. Our language was limited to English during the study. The last time we looked at the e-databases was August 2023. Case control studies were performed where MMC resulted in better wound healing than 5-FU. Researchers selected a total of 1023 trials and eventually selected six trials for data analysis. Four hundred and ninety one cases of glaucoma were treated with trabeculectomy. Among them, 246 were given MMC and 245 were given 5-FU during operation. Six trials showed that there was no statistical difference between MMC and 5-FU in the incidence of post-operative wound leak in glaucoma patients who received trabeculectomy (OR, 1.21; 95% CI, 0.63-2.30 p = 0.57); Five trials demonstrated that MMC was associated with a reduced risk of post-operative corneal damage compared to 5-FU injection (OR, 0.18; 95% CI, 0.06-0.56 p = 0.003); In both trials, the incidence of post-operative bleeding was not significantly different from that of 5-FU injected in the MMC group (OR, 0.33; 95% CI, 0.05-2.16 p = 0.25). Our results indicate that MMC is superior to 5-FU in the reduction of post-operative corneal injury. Additional comparisons between MMC and 5-FU are required in order to increase the reliability and effectiveness of these findings.

The purpose of this case report is to describe a case of continuous wear of a gas-permeable mini-scleral contact lens with a fluid reservoir of autologous serum (AS) combined with AS drops as a successful empirical and accessible alternative therapeutic option for refractory persistent epithelial defects in a patient with severe neurotrophic keratopathy (NK) due to severe dry eye disease and chronic contact lens wear. A 61-year-old Caucasian female with bilateral NK presented a history of multiple episodes of bilateral persistent epithelial defects, having already been submitted to three tectonic-penetrating keratoplasties in her left eye (OS). In May 2017, the patient developed de novo refractory central neurotrophic ulcers in both eyes (OU), unresponsive to conventional treatment with preservative-free lubricants, topical antibiotics, topical anti-inflammatory agents, and oral doxycycline. By March 2018, after initiating hourly AS eyedrops, the ulcer in her right eye (OD) improved to a smaller ulcer, while her OS presented complete graft re-epithelialization. In May 2018, her OD neurotrophic ulcer was complicated with fungal and subsequent bacterial secondary infection. Eventually, a therapeutic penetrant keratoplasty was required for her OD. Subsequently, her OD graft developed a de novo 6x6mm central persistent epithelial defect unresponsive to all the aforementioned therapeutic strategies. After months of unsuccessful treatment, a new therapeutic option was experimented with: a gas-permeable mini-scleral contact lens in combination with AS eyedrops. After two weeks of this treatment regimen, the corneal epithelium eventually started to regenerate, and four weeks later, the cornea was completely re-epithelized. To date, there are no signs of recurrence of the corneal epithelial defect/ulcer.

UNASSIGNED: To evaluate corneal epithelial changes and related factors in chronic ocular graft-versus-host disease (oGVHD) patients.
UNASSIGNED: 21 patients (35 eyes) with chronic oGVHD and 8 patients (12 eyes) without oGVHD after bone marrow transplantation were recruited for assessment involving in vivo confocal microscopy (IVCM) analysis, ocular surface parameter determination and tear cytokine level analysis. The IVCM corneal epithelial scoring system was used to evaluate corneal epithelial changes.
UNASSIGNED: There was a significant difference in the corneal epithelial score (p = .001) between the two groups. The corneal epithelial scores were significantly correlated with the corneal fluorescein staining scores (CFS, r = 0.463, p < .001), Schirmer\'s test (r = -0.389, p = .009) and tear cytokine levels of EGF (r = -0.491, p < .001) and APRIL (r = -0.318, p = .030).
UNASSIGNED: The depth of corneal epithelial defects can be estimated by the CFS. Corneal epithelial changes of chronic oGVHD are considered to be associated with lacrimal deficiency and a lack of EGF.

UNASSIGNED: To compare the efficacy, safety, and rate of healing on the corneal epithelial defect after pterygium surgery through the application of either 0.18% or 0.3% sodium hyaluronate (SH).
UNASSIGNED: A randomized, double-blind clinical trial was performed on patients who had pterygium surgery. Eighty-six patients were randomized to 2 groups that would receive either 0.18% SH or 0.3% SH. Measurements of area of the corneal epithelial defect using ImageJ freeware were performed. All corneal epithelial defects were measured immediately after the operation (Day 0) and for the next 3 days.
UNASSIGNED: The mean and SD of the area of corneal epithelial defect measured on postoperative Day 0, 1, and 2 were 9.13 ± 3.09 mm2, 5.61 ± 3.26 mm2, and 3.39 ± 2.70 mm2 for 0.18% SH group, and 8.96 ± 3.17 mm2, 4.03 ± 1.99 mm2, and 1.55 ± 1.23 mm2 for 0.3% SH group. There was no statistically significant difference of the initial area of the corneal epithelial defect on Day 0 between 0.18% and 0.3% SH group (p = 0.802). The area of the defects in the 0.3% SH group was significantly smaller than that of the 0.18% SH group on both Day 1 and Day 2 (p = 0.007, p < 0.001), respectively. Similarly, the 0.3% SH group exhibited a statistically significant higher (p < 0.001) rate of healing of the corneal epithelial defect over days 0 and 1 (4.94 ± 2.16 mm²/day) when compared to that of the 0.18% SH group (3.53 ± 1.66 mm²/day).
UNASSIGNED: With two commercial artificial tears, the corneal epithelial wound healing after pterygium surgery was faster in the 0.3% SH group than that of the 0.18% SH group. Superiority of 0.3% SH may be supported by the presence of epsilon-aminocaproic acid in this drug preparation. No significant adverse effects were exhibited during the short-term follow-up.

UNASSIGNED: To study the efficacy of 100% Leptospermum medical grade Manuka honey ointment in persistent corneal epithelial defects (CEDs).
UNASSIGNED: Case series.
UNASSIGNED: Case 1 was a 25-year-old female patient who presented to the cornea clinic with a persistent CED (3.5 mm), following acanthamoeba keratitis, that had failed to respond to heavy, frequent lubrication drops and ointment. Two weeks later, after starting Leptospermum honey ointment (4 times per day), the CED healed totally. Case 2 was a 48-year diabatic, single-eyed female patient who presented with a persistent CED (1.5 × 1.5 mm) that had failed to respond to heavy, frequent lubrication drops and ointment. The CED healed three weeks after starting Leptospermum honey ointment (4 times per day).
UNASSIGNED: Leptospermum honey ointment can be a potential treatment for persistent epithelial defect.

OBJECTIVE: To investigate the incidence, risk factors, clinical course, and outcomes of corneal epithelial defects (CED) following vitreoretinal surgery in a prospective study setting.
METHODS: This was a post-hoc analysis of all participants in DISCOVER intraoperative optical coherence tomography study. Subjects with CED 1d after surgery without intraoperative corneal debridement was defined as the postoperative CED group. Subjects who underwent intraoperative debridement were defined as intraoperative debridement group. Eyes were matched 2:1 with controls (eyes without postoperative CED) for comparative assessment. The primary outcomes were the incidence of CED on postoperative day one and the incidence of required intraoperative debridement. Secondary outcomes included time to defect closure, delayed healing (>2wk), visual acuity (VA) and presence of scarring at one year and cornea consult.
RESULTS: This study included 856 eyes that underwent vitreoretinal surgery. Intraoperative corneal debridement was performed to 61 (7.1%) subjects and postoperative CED developed spontaneously in 94 (11.0%) subjects. Significant factors associated with postoperative CED included prolonged surgical duration (P=0.003), diabetes mellitus (P=0.04), postoperative ocular hypotension (P<0.001). Prolonged surgical duration was associated with intraoperative debridement. Delayed defect closure time (>2wk) was associated with corneal scar formation at the end of the 1y in all epithelial defect subjects (P<0.001). The overall rate of corneal scarring for all eyes undergoing vitrectomy was 1.8%.
CONCLUSIONS: Prolonged duration of surgery is the strongest factor associated with both intraoperative debridement and spontaneous postoperative CED. Delayed defect closure is associated with a greater risk of corneal scarring at one year. The overall rate of corneal scarring following vitrectomy is low at <2%.

UNASSIGNED: The study aimed to investigate the effects of 2% hyaluronic acid (HA) on corneal epithelial defect after pterygium surgery in comparison with the control group, measured in terms of the healing rate of corneal epithelial defect and pain score after surgery.
UNASSIGNED: In this double-blind randomized clinical trial, fifty patients with primary pterygium were randomized into 2 groups: a control group or the group treated with a single topical application of 2% HA. Comprehensive ophthalmological examinations included measuring the area of corneal epithelium defect using ImageJ freeware and the pain score assessment after the operation.
UNASSIGNED: The mean and SD of the area of epithelial defect measured on postoperative Day 0, 1, and 2 were 10.89 ± 1.33 mm2, 5.04 ± 0.87mm2, and 2.44 ± 0.74 mm2 for the HA group, and 11.14 ± 1.11 mm2, 7.74 ± 1.17 mm2, and 5.31 ± 1.15 mm2 for the control group, respectively. While the initial area of the defect on Day 0 was essentially the same for both groups (p = 0.478), the area of the defect in the HA group was significantly smaller on both Day 1 and Day 2 (p < 0.001, p < 0.001), respectively. Similarly, the HA group exhibited a statistically significant higher rate of healing for the cornea epithelial defect over Day 0 and 1 compared to the control group (5.85 ± 0.89 mm2/day vs 3.14 ± 1.28 mm2/day, p < 0.001), respectively. The median (range) pain scores were evaluated at Day 0 was 7 (4-10) in the HA group and 7 (3-10) in the control group (p = 0.953). There was no statistically significant difference between two groups (p > 0.05) for Days 1, 2, and 3.
UNASSIGNED: A single topical application of 2% HA tended to accelerate the healing process of corneal epithelium defect after pterygium surgery without any observable adverse effects during short-term follow-up.

OBJECTIVE: To investigate the effect of topical insulin on epithelization in persistent epithelial defects (PED) refractory to usual treatment compared to autologous serum.
METHODS: Retrospective, consecutive case-control series.
METHODS: The charts of 61 consecutive patients with PED treated with topical insulin (case group) and 23 treated with autologous serum (control group) were reviewed. Primary efficacy end points were the percentage of patients in which epithelization was achieved, as well as the rate and time until epithelization. Secondary efficacy point was need for amniotic membrane transplantation (AMT) or other surgeries.
RESULTS: Mean time between PED diagnosis and start of topical insulin was 22.7 ± 18.5 days (range 13-115) and the mean area was 14.8 ± 16.2 mm2 (range 1.1-70.6). In the control group, mean time was 27.9 ± 16.8 days, mean epithelial defect area being 18.6 ± 15.0 mm2 (range 1.7-52.9). No differences in baseline characteristics were found between groups (p > 0.05). Epithelization was achieved in 51 patients (84%) on insulin and 11 patients (48%) on autologous serum (p = 0.002). In those patients, mean time until reepithelization was 32.6 ± 28.3 days (range 4-124) in the insulin group and 82.6 ± 82.4 days (range 13-231) in the autologous serum group (p = 0.011). The need for AMT was significantly lower in the insulin group (p = 0.005). PED recurrence was higher in patients treated on autologous serum (43%) compared with insulin (11%) (p = 0.002).
CONCLUSIONS: Topical insulin is an effective treatment and safely promotes healing of PED. In our series, topical insulin presented better epithelization outcomes than autologous serum and could thus be considered as a first-line treatment.