Corneal Epithelial Defects Research Articles

Blood‐derived trophic factors for the treatment of ocular surface diseases

The use of blood‐derived products (Eye Drop of Human Origin—EDHO; in Italian: Emocomponents for Not Transfusional Use, EUNT) for the treatment of various ocular surface diseases has become increasingly utilized in ophthalmic practice over the years. In particular, they are recommended as a third line option, when conventional tear substitutes, or active drugs, such as corticosteroids or Cyclosporine A, result unsuccessful in controlling either signs and, perhaps most importantly, subjective symptoms of discomfort and pain. The rationale for their use is based on the stimulation of cell proliferation and migration through the supply of metabolically active substances, in particular growth factors, and definitely mimicking the function of natural tears.EDHO have been used for the treatment of various ocular surface diseases, including dry eye, persistent corneal epithelial defect, corneal ulcer, neurotrophic keratitis, ocular surface burn, recurrent corneal erosion and limbal stem cell deficiency. However, the therapeutic potential of these products is still to be fully explored, as randomized clinical trials and internationally recognized harmonized guidelines are still needed to provide better evidence, improve quality of the final products and lead to a more widespread use of these therapies in daily clinical practice. The autologous source is still quite popular, although allogeneic sources appear to be a promising innovation. These might offer the solution of obtaining in advance products tailored for each patient and ocular surface disease, at scalable concentrations based on the severity of the disease and clinical parameters. There remain many unanswered questions regarding what might be considered optimal treatment, sketched as “The 5 Ws (and 2 H) for blood based eye drops”, to quote a review from our group (doi: 10.3390/jcm8091478). This presentation will discuss: 1. who is the patient to be treated, in terms of disease type, severity, and stage?; 2. Why is an EDHO needed, in terms of a target indication?; 3. When is it appropriate to prescribe an EDHO therapy?; 4. Where are EDHO be dispensed, and is a national/regional program a feasible solution to optimize resources?; 5. What is the EDHO of choice, which source and preparation are targeted for a given patient? And further: 1. how is EDHO standardized in terms of processing to ensure an optimal dilution, solvent, dispenser, storage time?; 2. How is EDHO delivered to the ocular surface, in terms of form, dose‐size modulation, length of treatment?An interdisciplinary work with transfusional medicine specialists is imperative to share information and competences, to achieve a better clinical management.

Topical Insulin in Neurotrophic Keratopathy: A Review of Current Understanding of the Mechanism of Action and Therapeutic Approach.

Neurotrophic keratopathy is a corneal disease characterized by impaired corneal innervation. It can lead to corneal epithelial defects, ulcerations, and perforations. Topical insulin has been shown to be effective in treating this disorder. Insulin is a growth factor that can promote corneal epithelial cell proliferation and migration. In addition, it can also inhibit corneal epithelial cell apoptosis. Topical insulin has previously been found to enhance corneal wound healing. This article reviews the current understanding of the mechanism of action of topical insulin in the treatment of neurotrophic keratopathy.

Potential Benefits of Integrin αvβ3 Antagonists in a Mouse Model of Experimental Dry Eye.

The purpose of this study was to extensively evaluate the efficacy of integrin αvβ3 antagonists for the treatment of experimental dry eye (EDE). Vitronectin, an αvβ3 ligand, was used to induce tumor necrosis factor-α gene expression in human THP-1 macrophages. To induce EDE, C57BL/6 mice were housed in a low-humidity controlled environment chamber and injected subcutaneously with scopolamine for 7 days. Subsequently, αvβ3 antagonists, including RGDfD, c(RGDfD), c(RGDiD), c(RGDfK), ATN-161, SB273005, and cilengitide, were administered topically to EDE animals under controlled environment chamber conditions. Corneal epithelial damage in EDE was assessed by fluorescein staining. The density of conjunctival goblet cells and secretion of tears was measured by period acid-Schiff staining and phenol red-impregnated cotton threads, respectively. Inflammation markers, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-17A, and metalloproteinase (MMP)-9, in the pooled cornea and conjunctiva tissues were examined by real-time polymerase chain reaction. The inhibitory effects of αvβ3 antagonists on the vitronectin-induced tumor necrosis factor-α gene expression and integrin-mediated inflammatory signaling were validated in THP-1 macrophages. αvβ3 antagonists ameliorated the impairment of the corneal epithelial barrier with varying therapeutic efficacies, compared with vehicle-treated mice. c(RGDfD) and c(RGDiD) significantly protected against goblet cell loss, tear reduction, and proinflammatory gene expression in EDE. Topical applications of αvβ3 antagonists yield therapeutic benefits in EDE by promoting corneal epithelial defect healing and reducing inflammation. Antagonistic targeting αvβ3 may be a novel promising strategy to treat patients with dry eye disease.

Outcomes and success of amniotic membrane transplantation for the treatment of corneal diseases#

Purpose The amniotic membrane (AM), the inner layer of the placenta, is a semitransparent, avascular, and thin tissue that is useful due to its structure. Amniotic membrane transplantation (AMT) avoids the need for keratoplasty to prevent corneal perforating. The purpose of the study was to evaluate the visual (gain of or no change in visual acuity) and corneal outcomes (closure of the ulcer or corneal healing) of AMT in patients with ocular surface diseases. Materials and methods This was a retrospective case control study (success or failure of the surgery). It was undertaken at a single academic center. The study cohort consisted of subjects with ocular surface diseases. Patients were treated with AMT for refractory ocular surface diseases. They were divided into five subgroups according to the preoperative diagnosis. The technique of AMT used was the onlay method with two layers of AM. Primary outcome measures included best corrected visual acuity (BCVA), the number of AMTs, and reepithelization of the corneal epithelium at the end of the treatment. Two weeks to six months were given to consider epithelial closure. Treatment success was defined as corneal healing within 6 months. Results A total of the 66 eyes of 66 patients (39 male/27 female) with a mean age of 44 ± 23 years (range 1–88 years) were included in the study. A single AMT procedure achieved epithelial closure in 74.2% (n = 49) of the eyes (53% in <15 days, 19.6% in 15–30 days, and 1.5% in 1–6 months). The fastest reepithelization occurred in neurotrophic keratopathy, 76.9% of which cases occurred within 15 days after the AMT procedure. Treatment failure was observed in five patients (7.5%), four with keratitis and one with neurotrophic keratopathy. The highest closure rates were found in persistent epithelial defects, graft-versus-host disease (GvHD), and bullous keratopathy, although there was no statistically significant difference in BCVA. Pairwise comparisons were made of neurotropic keratoplasty versus bullous keratopathy (P = 0.025), neurotrophic keratopathy versus keratitis (P = 0.004), GVHD versus keratitis (P = 0.003), and lastly, GvHD versus bullous keratopathy (P = 0.023). Conclusions AMT is a safe, valuable, and fast treatment technique to treat corneal epithelial defects stemming from different etiologies that are refractory to conventional treatment.

Chinese expert consensus on the application of amniotic membrane in the treatment of corneal and ocular surface diseases (2023)

Amniotic membrane (AM) can promote epithelialization, inhibit inflammation and be antimicrobial. It has been widely used in the clinical treatment of corneal epithelial and stromal defects. However, the misuse and abuse of AM might aggravate the primary disease and even lead to the loss of the best timing for other surgical interventions. Based on domestic and foreign clinical practice guidelines and medical evidence, the Cornea Group of Ophthalmology Branch of Chinese Medical Association has formed consensus opinions about the indications, surgical techniques and perioperative management of AM transplantation, so as to standardize the application of AM in the treatment of corneal and ocular surface diseases.

Analysis of long-term outcomes of penetrating keratoplasty for congenital corneal opacity

Objective: To investigate the long-term outcomes of corneal grafts after penetrating keratoplasty(PK) for congenital corneal opacity(CCO) in children aged 0 to 5 years and the related influencing factors. Methods: It was a retrospective series case study. Data of 39 children (55 eyes) who underwent PK surgery due to CCO in the keratology Department of Beijing Tongren Hospital from April 2014 to April 2018 and were followed up for more than 30 months were collected. Among them, there were 17 males (43.6%) and 22 females (56.4%). The age at operation was (16.2±13.3) months, and the follow-up time was (46.4±13.8) months. Clinical data such as basic information, preoperative diagnosis, operation age, operation method and postoperative complications were recorded. The corneal graft transparency was analyzed according to preoperative diagnosis, corneal neovascularization area, age at surgery, monocular or binocular surgery interval, primary surgery type and further surgery, and postoperative complications were observed. Results: At 12 months, 24 months and the last follow-up after PK, 78.2% (43/55), 70.9% (39/55) and 58.2% (32/55) of the affected eyes had clear corneal grafts, respectively.There was no statistical significance between Peters anomaly and sclerocornea (P>0.05), while the extent of neovascularization in the limbus had a significant effect on corneal graft transparency, and graft opacity was more likely to occur in patients with vessel area exceeding 2 quadrants (P<0.05).The highest corneal graft transparency was found in children aged 1 to 3 years 80.8%(21/26) (P<0.05), followed by children younger than 6 months (7/15).The translucency rate of the corneal graft was higher in patients undergoing unilateral surgery than in those undergoing bilateral surgery (P<0.05).Translucency of corneal graft was higher in children with simple surgery than with combined surgery (P<0.05), however, cataract surgery after PK had no significant effect on corneal graft transparency (P>0.05).The postoperative complications mainly included immune rejection in 19 eyes (34.5%), complicated cataract in 13 eyes (23.6%), glaucoma in 7 eyes (13.2%), persistent corneal epithelial defect in 7 eyes (13.2%). Conclusions: After PK in children with CCO, the transparent rate of corneal grafts decreases gradually with time, but the long-term translucency of corneal grafts can still be obtained. The range of corneal neovascularization, age at the time of surgery, whether the surgery was binocular and whether the surgery was combined had an effect on the transparency of corneal graft.

Модифицированный способ субконъюнктивального введения антиметаболитов в хирургии глаукомы

Purpose. Comparative evaluation of the clinical and functional results of post-operative adjuvant subconjunctival administration of 5-fluororacil after a non-penetrating deep sclerectomy (npdS) compared to the control group. Material and methods. A retrospective study was conducted of two groups of patients with primary open-angle glaucoma who had undergone npdS and received at least 1 subconjunctival injection of 5-fluorouracil in the postoperative period. Group 1 is patients who have received post-surgical 5-fluoride injection using a standard procedure. group 2 — patients who received the injection according to the proposed method. The comparison included: best correction visual acuity (BcVa), intraocular pressure (Iop), frequency of corneal complications. Results. Demographic characteristics and preoperative BcVa and Iop parameters did not differ between the compared groups. Corneal epithelial defects stained with fluorescein were statistically significantly more common in group 1 compared to group 2, p &lt; 0.001. The highest decrease of Iop (p = 0.042) and lower loss of BcVa (p &lt; 0.001) 4 weeks after npdS was observed in group 2. Conclusions. The use of the modified method provides greater safety and efficacy of 5-fluorouracil administration in the postoperative period of npdS compared to the control group. Keywords: 5-fluorouracil, glaucoma, corneal erosion, toxicity, prevention of complications, injection

Prevalence of Keratopathy in Vernal Keratoconjunctivitis

Background: Vernal keratoconjunctivitis is a chronic allergic eye disease that primarily affects young individuals and can lead to significant discomfort and visual impairment. Keratopathy, in the context of Vernal Keratoconjunctivitis (VKC), refers to corneal changes and complications that can occur as a result of this chronic allergic eye condition. VKC primarily affects the conjunctiva and the cornea, and keratopathy is a significant concern due to its potential to cause visual impairment. Objective: To determine the frequency of keratopathy in vernal keratoconjunctivitis. Study Design: Cross-sectional. Settings: Sindh Institute of Ophthalmology and visual sciences at LUMHS Eye Hospital Hyderabad Pakistan. Duration: From February 16, to August 15, 2019. Methods: All the patients with VKC, aged 5-15 years and both genders were included. History was taken from patient or parent about presenting complains and duration of disease. Clinical (slit lamp) examination was performed to look for corneal lesions. Both eyes of each patient were examined for corneal involvement, including SPEE (positive Florescence staining), corneal epithelial defects, corneal shield ulcer and corneal subepithelial scars. Florescence staining with blue filter was used where indicated. All the data was entered in the proforma and analyzed by SPSS version 20. Results: Total 232 patients were studied, most of the patients 84.1%, belonged to age group of 5-10 years, while 15.9% presented with age range of 11-15 years. Males were most common 78.0%. Frequency of keratopathy was 22.0%. Most of the cases 51.3%, had &gt;1 years duration. According to type of keratopathy, superior punctate epithelial erosions was most common type among 35.3% patients out of 51, scarring was among 24.5% patients, shield ulcer was among 9.8% patients and macro erosion was in 2 patients. No significant impact was found of age on Prevalence of keratopathy, (p-0.419). Male gender, duration of VKC and bilateral eyes were significantly associated with Prevalence of keratopathy, (p-0.001). Conclusion: It was concluded that frequency of keratopathy in vernal keratoconjunctivitis is 22.0%.

Long-term PM2.5 exposure disrupts corneal epithelial homeostasis by impairing limbal stem/progenitor cells in humans and rat models

BackgroundLimbal stem/progenitor cells (LSPCs) play a crucial role in maintaining corneal health by regulating epithelial homeostasis. Although PM2.5 is associated with the occurrence of several corneal diseases, its effects on LSPCs are not clearly understood.MethodsIn this study, we explored the correlation between PM2.5 exposure and human limbal epithelial thickness measured by Fourier-domain Optical Coherence Tomography in the ophthalmologic clinic. Long- and short-term PM2.5 exposed-rat models were established to investigate the changes in LSPCs and the associated mechanisms.ResultsWe found that people living in regions with higher PM2.5 concentrations had thinner limbal epithelium, indicating the loss of LSPCs. In rat models, long-term PM2.5 exposure impairs LSPCs renewal and differentiation, manifesting as corneal epithelial defects and thinner epithelium in the cornea and limbus. However, LSPCs were activated in short-term PM2.5-exposed rat models. RNA sequencing implied that the circadian rhythm in LSPCs was perturbed during PM2.5 exposure. The mRNA level of circadian genes including Per1, Per2, Per3, and Rev-erbα was upregulated in both short- and long-term models, suggesting circadian rhythm was involved in the activation and dysregulation of LSPCs at different stages. PM2.5 also disturbed the limbal microenvironment as evidenced by changes in corneal subbasal nerve fiber density, vascular density and permeability, and immune cell infiltration, which further resulted in the circadian mismatches and dysfunction of LSPCs.ConclusionThis study systematically demonstrates that PM2.5 impairs LSPCs and their microenvironment. Moreover, we show that circadian misalignment of LSPCs may be a new mechanism by which PM2.5 induces corneal diseases. Therapeutic options that target circadian rhythm may be viable options for improving LSPC functions and alleviating various PM2.5-associated corneal diseases.

Injectable hydrogels derived from marine polysaccharides as cell carriers for large corneal epithelial defects

Injectable hydrogels have been employed for sutureless repair of corneal epithelial defects, which can perfectly fit the defect sites and minimize the associated discomfort. However, numerous hydrogels are ineffective in treating large corneal epithelial defects and still suffer from poor biocompatibility or weak applicability when used as cell carriers. Herein, hydroxypropyl chitin/carboxymethyl chitosan (HPCT/CMCS) temperature-sensitive hydrogels are fabricated, and their physicochemical properties and suitability for corneal epithelial repair are investigated. The results demonstrate that HPCT/CMCS hydrogels have excellent temperature sensitivity between 20 and 25 °C and a transparency of over 80 %. Besides, HPCT/CMCS hydrogels can promote cell proliferation and facilitate cell migration of primary rabbit corneal epithelial cells (CEpCs). A rabbit large corneal epithelial defect model (6 mm) is established, and CEpCs are transplanted into defect sites by HPCT/CMCS hydrogels. The results suggest that HPCT/CMCS/CEpCs significantly enhance the repair of large corneal epithelial defects with a healing rate of 99.6 % on day 8, while reducing inflammatory responses and scarring formation. Furthermore, HPCT/CMCS/CEpCs can contribute to the reconstruction of damaged tissues and the recovery of functional capacities. Overall, HPCT/CMCS hydrogels may be a feasible corneal cell carrier material and can provide an alternative approach to large corneal epithelial defects.

Development and validation of a reliable rabbit model of limbal stem cell deficiency by mechanical debridement using an ophthalmic burr

A simple and reproducible method is necessary to generate reliable animal models of limbal stem cell deficiency (LSCD) for assessing the safety and efficacy of new therapeutic modalities. This study aimed to develop and validate a rabbit model of LSCD through mechanical injury. The corneal and limbal epithelium of New Zealand White rabbits (n = 18) were mechanically debrided using an ophthalmic burr (Algerbrush II) with a 1.0-mm rotating head after 360° conjunctival peritomy. The debrided eyes were serially evaluated for changes in corneal opacity, neo-vascularization, epithelial defect and corneal thickness using clinical photography, slit lamp imaging, fluorescein staining, and anterior segment optical coherence tomography scanning (AS-OCT). Following this, an assessment of histopathology and phenotypic marker expression of the excised corneas was conducted. The experimental eyes were grouped as mild (n = 4), moderate (n = 10), and severe (n = 4) based on the grade of LSCD. The moderate group exhibited abnormal epithelium, cellular infiltration in the stroma, and vascularization in the central, peripheral, and limbal regions of the cornea. The severe group demonstrated central epithelial edema, peripheral epithelial thinning with sparse goblet cell population, extensive cellular infiltration in the stroma, and dense vascularization in the limbal region of the cornea. A significant decrease in the expression of K12 and p63 (p < 0.0001) was observed, indicating the loss of corneal epithelium and limbal epithelial stem cells in the LSCD cornea. This study demonstrates that the Alger brush-induced mechanical debridement model provides a reliable model of LSCD with comprehensive clinic-pathological features and that is well suited for evaluating novel therapeutic and regenerative approaches.

Preservative-Free Topical Anesthetic Unit-Dose Eye Drops for the Management of Postoperative Pain Following Photorefractive Keratectomy.

Ocular pain is a common complication following photorefractive keratectomy (PRK). The level of patient satisfaction with current pain control strategies is not high. This study aims to assess the efficacy and safety of a novel regimen of preservative-free oxybuprocaine hydrochloride 0.4% unit-dose eye drops for post-PRK pain control. In a contralateral eye study, 144 eyes of 72 patients who underwent bilateral transepithelial PRK (TransPRK) were stratified into experimental and control groups. The experimental group received preservative-free oxybuprocaine hydrochloride 0.4% unit-dose eye drops five times daily postoperatively until complete epithelial healing, while the control group received sodium hyaluronate 0.2% instead. The main outcome measures were pain scores assessed by the verbal rating scale and visual analogue scale (VRS, VAS), the corneal epithelial defect (CED) area, epithelial healing duration evaluated by slit-lamp biomicroscopy and anterior segment optical coherence tomography (AS-OCT), and endothelial cell density (ECD) measured before and 1 month after surgery. Pain scores assessed by VRS and VAS were significantly lower in the experimental group 8h after surgery, and 1, 2, and 3days postoperatively (P < 0.001). The mean CED area showed no significant differences between the two groups at different follow-ups (P value > 0.05). The corneal epithelial healing had a mean duration of 3.32 ± 0.47 days in both studied groups and was parallel in both eyes of each patient. In each group, 49 eyes (68%) and 72 eyes (100%) had a fully epithelialized surface on the third and fourth postoperative days, respectively. No significant changes were observed in the mean ECD 1 month following surgery in both groups (P value > 0.05). Preservative-free oxybuprocaine hydrochloride 0.4% unit-dose eye drops are effective and safe in controlling early postoperative pain following TransPRK. The availability of the single-dose unit preparation can overcome the problem of topical anesthetic abuse. ClinicalTrials.gov Identifier: NCT05733741.

Evaluation of Corneal Nerve Regeneration After Minimally Invasive Corneal Neurotization.

To evaluate the corneal nerve regeneration after minimally invasive corneal neurotization (MICN) and to further clarify the recovery patterns of sensory and trophic functions of the corneal nerves. A retrospective cohort study based in the Shanghai Ninth People's Hospital. Eighteen patients (18 eyes) who underwent MICN for neurotrophic keratopathy due to intracranial surgery was conducted to analyze their follow-up data at 6, 12, 18, and 24 months after surgery. At 12 months postoperatively, the growth of the central and peripheral corneal nerve fiber density (CNFD) was 11.47±8.56 and 14.73±8.08n/mm 2 with subsequent improvement slowing down, and the patient's corneal epithelium defect was healed ahead of the accomplishment of corneal nerve regeneration. The number of dendritic cells also reached its peak. At 18 months postoperatively, the recovery of central and peripheral corneal sensation was 37.22±23.06mm and 39.38±18.08mm with no subsequent improvement, and the growth of the central and peripheral corneal nerve branch density (CNBD) was 29.69±11.05 and 43.75±1.41n/mm 2 , with a positive and significant correlation between corneal sensation and CNBD (at central r =0.632, P <0.005; at peripheral r =0.645, P <0.005). At 24 months postoperatively, mean CNFD, CNBD, and corneal sensation recovered significantly compared with preoperative, but a few patients' corneal sensation recovered insignificantly with good CNFD recovery and poor CNBD recovery. After MICN, the trophic function of the corneal nerve recovers before the sensory function, and in particular, the recovery of sensation is based on the coexistence of the corneal nerve trunk and branches.

An easy and safe method of subconjunctival injection of antimetabolites in glaucoma surgery

Aim: The use of 5-fluorouracil in glaucoma surgery is associated with a high risk of corneal complications, as even minimal doses of the drug at the ocular surface inhibit corneal epithelial cell division and lead to corneal epitheliopathy and erosion. The aim of this study was to evaluate the clinical and functional results of the proposed method of postoperative adjuvant subconjunctival injection of 5-fluorouracil after non-penetrating deep sclerectomy (NPDS) in comparison with the control group. Methods: Patients with primary open-angle glaucoma who underwent NPDS and received at least 1 subconjunctival injection of 5-fluorouracil in the postoperative period were included in a two-group retrospective comparative study. Patients who received a subconjunctival injection of 5-fluorouracil after surgery using the standard technique were included in Group 1; Group 2 included patients who received an injection using the proposed method. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), rate of corneal complications, and number of office visits during the first 4 weeks after surgery were analysed. Results: The compared groups did not differ in demographic characteristics, preoperative BCVA, and IOP parameters. Fluorescein-stained corneal epithelial defects were statistically significantly more frequent in Group 1 compared to Group 2, P &lt; 0.001. Four weeks post NPDS IOP reduction was greater in Group 2, P = 0.042. Mean BCVA loss was 1.9 lines in Group 1 and 1.3 lines in Group 2, P &lt; 0.001. The number of follow-up visits during the first month after surgery was lower in Group 2 than in Group 1, P = 0.002. Conclusions: The proposed method was simple and effective in reducing the risk of corneal epithelial defects after subconjunctival injection of 5-fluorouracil, significantly improving clinical and functional outcomes of NPDS and reducing the need for outpatient visits.

Syphilitic uveitis in HIV-positive patients: report of a case series, treatment outcomes, and comprehensive review of the literature.

To report the clinical characteristics, treatment and outcomes of active syphilitic uveitis in human immunodeficiency virus (HIV) positive patients and compare them with the previously published data. Retrospective analysis of the case series from an infectious disease center in southern China was conducted. Comprehensive review of previously published cases of HIV positive syphilitic uveitis was conducted using the PubMed and Web of Science databases and the references listed in the identified articles. Twelve HIV positive patients with active syphilitic uveitis were collected. All were male, with age of 36.3y (range 27 to 53y). Five (41.7%) had a history of syphilis, and three of them had received anti-syphilis treatment. Ocular manifestations included corneal epithelial defect (13%), complicated cataract (17.4%), vitreous opacity (82.6%), optic disc edema (26.1%), macular edema (30.4%), neuro-retinitis (43.5%), and retinal hemorrhage (26.1%). After standardized syphilitic treatment, intraocular inflammation was reduced and vision improved in all cases. The literature review summarizes 105 previously reported cases of HIV positive syphilitic uveitis. High serum rapid plasma regain (RPR) titers may be associated with severe uveitis and poor vision. Treatment with penicillin, ceftriaxone sodium, or penicillin plus benzylpenicillin instead of using benzylpenicillin alone can significantly improve best-corrected visual acuity (BCVA) in HIV positive ocular syphilis patients. For HIV positive syphilitic uveitis patients, prompt diagnosis and appropriate treatment and follow-up are paramount. In our series, the clinical manifestations are diverse. Syphilis patients treated by penicillin G or long-acting penicillin before may still develop syphilitic uveitis. Patients who relapse after long-term penicillin treatment can still benefit from penicillin G.

Good Outcome of Corneal Ulcer With Hypopion After Long Use of Contact Lens

Introduction: Microbial keratitis is a corneal infection caused by microorganisms and is characterized by a profound corneal epithelial defect that infects the cornea and causes severe and progressive visual loss. In recent years, the incidence of microbial keratitis has increased. One of the critical risk factors for increasing this incidence is using contact lenses. As the number of contact lens users increases, the number of corneal ulcers associated with contact lenses also increases. Case Presentation: A 25-year-old man was admitted to the emergency department with a complaint of gradually blurry vision in his left eye four days after using contact lenses for overnight uses since the previous few days and did not routinely clean contact lenses or replace contact lens cleaning fluid. The visual acuity of the patient's left eye was hand movement with conjunctival and pericorneal injection in the conjunctiva and 6 x 7 mm stromal level infiltrate, blurred margin, and whitish color in the center of the cornea. After 28 days of treatment, an examination showed the patient's left eye improvement. Visual acuity was 3/60, conjunctival injection disappeared, corneal swelling significantly resolved, hypopyon disappeared, and ulcer completely re-epithelialized. Conclusions: Empirical therapy with broad-spectrum antibiotics and other adjunctive therapy has a good outcome in treating contact lens-related corneal ulcers.

Sustained Inhibition of VEGF and TNF-α Achieves Multi-Ocular Protection and Prevents Formation of Blood Vessels after Severe Ocular Trauma.

This study aimed to develop a clinically feasible and practical therapy for multi-ocular protection following ocular injury by using a thermosensitive drug delivery system (DDS) for sustained delivery of TNF-α and VEGF inhibitors to the eye. A thermosensitive, biodegradable hydrogel DDS (PLGA-PEG-PLGA triblock polymer) loaded with 0.7 mg of adalimumab and 1.4 mg of aflibercept was injected subconjunctivally into Dutch-belted pigmented rabbits after corneal alkali injury. Control rabbits received 2 mg of IgG-loaded DDS or 1.4 mg of aflibercept-loaded DDS. Animals were followed for 3 months and assessed for tolerability and prevention of corneal neovascularization (NV), improvement of corneal re-epithelialization, inhibition of retinal ganglion cell (RGC) and optic nerve axon loss, and inhibition of immune cell infiltration into the cornea. Drug-release kinetics was assessed in vivo using an aqueous humor protein analysis. A single subconjunctival administration of dual anti-TNF-α/anti-VEGF DDS achieved a sustained 3-month delivery of antibodies to the anterior chamber, iris, ciliary body, and retina. Administration after corneal alkali burn suppressed CD45+ immune cell infiltration into the cornea, completely inhibited cornea NV for 3 months, accelerated corneal re-epithelialization and wound healing, and prevented RGC and optic nerve axon loss at 3 months. In contrast, anti-VEGF alone or IgG DDS treatment led to persistent corneal epithelial defect (combined: <1%; anti-VEGF: 15%; IgG: 10%, of cornea area), increased infiltration of CD45+ immune cells into the cornea (combined: 28 ± 20; anti-VEGF: 730 ± 178; anti-IgG: 360 ± 186, cells/section), and significant loss of RGCs (combined: 2.7%; anti-VEGF: 63%; IgG: 45%) and optic nerve axons at 3 months. The aqueous humor protein analysis showed first-order release kinetics without adverse effects at the injection site. Concomitant inhibition of TNF-α and VEGF prevents corneal neovascularization and ameliorates subsequent irreversible damage to the retina and optic nerve after severe ocular injury. A single subconjunctival administration of this therapy, using a biodegradable, slow-release thermosensitive DDS, achieved the sustained elution of therapeutic levels of antibodies to all ocular tissues for 3 months. This therapeutic approach has the potential to dramatically improve the outcomes of severe ocular injuries in patients and improve the therapeutic outcomes in patients with retinal vascular diseases.

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.

Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy.

Neurotrophic keratopathy is a persistent defect of the corneal epithelium, with or without stromal ulceration, due to corneal nerve deficiency caused by a variety of etiologies. The treatment options for neurotrophic keratopathy are limited. In this study, an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor (CTH-mNGF). Its effectiveness was evaluated in corneal denervation (CD) mice and patients with neurotrophic keratopathy. In the preclinical setting, CTH-mNGF was assessed in a murine corneal denervation model. CTH-mNGF was transparent, thermosensitive, and ensured sustained release of mNGF for over 20 hours on the ocular surface, maintaining the local mNGF concentration around 1300 pg/mL in vivo. Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice. A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy. Patients received topical CTH-mNGF twice daily for 8 weeks. Fluorescein sodium images, Schirmer's test, intraocular pressure, Cochet-Bonnet corneal perception test, and best corrected visual acuity were evaluated. In total, six patients (total of seven eyes) diagnosed with neurotrophic keratopathy were enrolled. After 8 weeks of CTH-mNGF treatment, all participants showed a decreased area of corneal epithelial defect, as stained by fluorescence. Overall, six out of seven eyes had fluorescence staining scores < 5. Moreover, best corrected visual acuity, intraocular pressure, Schirmer's test and Cochet-Bonnet corneal perception test results showed no significant improvement. An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes. This study demonstrates that CTH-mNGF is transparent, thermosensitive, and has sustained-release properties. Its effectiveness in healing corneal epithelial defects in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy, being convenient and cost effective.

Ocular Trauma in Children: An Epidemiological Study.

This study aimed to determine the epidemiology of eye injuries in children and the influential factors involved. Eighty cases of confirmed ocular trauma were included in this cross-sectional study. Data were obtained via a checklist containing demographic information, site of the insult, the interval between the injury and physician visit, trauma mechanism, and medical history, including previous history of ocular trauma. Among 80 children with ocular trauma, 72.5% (n = 58) were boys. A marked preponderance (46.2%) of injuries was seen in the age group younger than 6 years. The youngest patient was a 1-year-old, and the oldest was aged 17. Most (76.25%) of the incidents occurred indoors. A total of 67.5% of accidents were induced by sharp objects (knife and glass). Most accidents occurred in spring, whereas the least number of accidents occurred in winter. The corneoscleral laceration was the most common manifestation, followed by the laceration of the iris, uveal prolapse, hyphema, and cataracts. Furthermore, rare cases of retinal detachment, hypopyon, and corneal epithelial defects were seen. The highest incidents of ocular trauma occurred in boys, especially those younger than 6 years. The high number of sharp object injuries is also concerning. These findings provide us with evidence that further educational interventions and supervision are required in these groups to minimize the possible devastating injuries before the opportunity even arises.