Persistent Corneal Epithelial Defects Research Articles

Anterior stromal micropuncture for the treatment of persistent corneal epithelial graft defects after penetrating keratoplasty

Persistent corneal graft erosion or persistent epithelial corneal defect is a frequent complication of penetrating keratoplasty. Its development can be contributed by the dry eye syndrome, rare blinking, lagophthalmos, symblepharon, viral infection, autoimmune aggression, and the use of epithelial-toxic eye drops. The article presents three clinical observations of patients who developed persistent corneal graft erosion after penetrating keratoplasty. Due to the ineffectiveness of local conservative therapy for more than 3 weeks, anterior stromal corneal micropuncture was performed. After the procedure, there was a gradual epithelial proliferation, complete healing of the corneal surface was observed 10-16 days after the manipulation, the follow-up period was at least 1 year. The mechanism of action of stromal micropuncture is associated with the creation of a porous surface with better adhesion properties, as well as with the activation of the production of extracellular matrix glycoproteins such as fibronectin, type IV collagen and laminin, which are necessary for stable adhesion of the epithelium. The use of stromal micropuncture of the donor flap in the treatment of post-keratoplasty persistent corneal epithelial defect was proposed for the first time.

Progress in research on persistent corneal epithelial defects

Progress in research on persistent corneal epithelial defects

Topical insulin for refractory persistent corneal epithelial defects.

To evaluate insulin eye drops for persistent epithelial defects (PEDs) that are refractory to usual treatment in clinical practice and to analyze how it may improve epithelization. A prospective non-randomized hospital-based study was performed. Patients with PEDs that were refractory to conventional treatment were treated with insulin eye drops four times a day. Patients' demographics, PED etiology, concomitant treatments, and comorbidities were reviewed. The rate of PED closure and epithelial healing time were considered the primary outcome measures. 21 patients were treated with insulin drops (12 females and 9 males; mean age 72.2 years). Mean PED area before treatment was 17.6 ± 16.5 mm2 (median 13.2; range 3.9-70.6). PED comorbidities included seven eyes with infectious keratitis (33%), five eyes with calcium keratopathy (24%), ocular surgery on three eyes (14%), three eyes with lagophthalmos (14%), two eyes with bullous keratopathy (10%), and one patient with herpetic eye disease (5%). The eyes of 17 patients (81%) with refractory PEDs had reepithelized and four patients (19%) had still presented an epithelial defect by the end of the study follow-up period, although it had decreased in size. In patients where PED closure was achieved, mean time until reepithelization was 34.8 ± 29.9 days (median 23; range 7-114). In the remaining patients, a mean area reduction of 91.5% was achieved for the PEDs. Topical insulin can promote and accelerate corneal reepithelization of refractory PEDs. It also offers many other advantages, including excellent tolerance, availability, and cost-effectiveness.

Prevalence of Persistent Corneal Epithelial Defects in Chronic Ocular Graft-Versus-Host Disease

To establish the prevalence, clinical characteristics, and risk factors for persistent corneal epithelial defects (PED) in patients with chronic ocular graft-versus-host disease (oGVHD) and to determine visual outcomes after healing. Retrospective cohort study. A chart review was conducted of patients in whom chronic oGVHD was diagnosed between January 2011 and December 2018 and their demographic and clinical characteristics were collected. Data were analyzed to determine prevalence of PED, and multivariate logistic regression was performed to determine the risk factors associated with it. A total of 405 patients at a mean age of 60 ± 13 years in whom chronic oGVHD was diagnosed; 58% were men. The prevalence of PED was 8.1%. The median time for PED development after hematopoietic stem cell transplantation was approximately 24months. Median time to PED resolution was 4.5weeks after starting therapy. The mean best-corrected visual acuity declined by 2 lines post-PED resolution. The prevalence rates of corneal ulcer and perforation were 6.2% and 4.0%, respectively, over 8 years. Logistic regression analysis, used to determine factors associated with PED, showed diabetes (P= .006), limbal stem cell deficiency (LSCD) (P= .02), filamentary keratitis (P= .02), subconjunctival fibrosis (P= .02), and a higher National Institutes of Health (NIH) oGVHD score (P= .01) were significant risk factors for PED development. The study found the prevalence rate of PED, corneal ulceration, and corneal perforation in chronic oGVHD to be 8.1%, 6.2%, and 4%, respectively. Analysis showed that oGVHD patients with diabetes, LSCD, filamentary keratitis, subconjunctival fibrosis, and a high NIH score were at higher risk of developing severe corneal disease.

Allogenic simple limbal epithelial transplantation (alloSLET) from cadaveric donor eyes in patients with persistent corneal epithelial defects

Background/aimTo describe the clinical outcome of allogenic simple limbal epithelial transplantation (alloSLET) utilising tissue from cadaveric donor eyes after failed re-epithelialisation of the corneal surface.MethodsMedical records of 14 eyes from...

Topical Umbilical Cord Serum for Corneal Epithelial Defects after Diabetic Vitrectomy.

PurposeTo evaluate the role of topical umbilical cord serum (TUCS) therapy in treating corneal epithelial defects (CEDs) after diabetic vitrectomy.MethodsIn this double-masked, randomized clinical trial, we included 80 eyes of 80 patients who were candidates for vitrectomy due to proliferative diabetic retinopathy complications. In cases of corneal edema obscuring the fundus view during surgery, the corneal epithelium was removed using a 6-mm trephine and a blade no.15. The day after the surgery, patients were randomly divided into two groups: (1) the TUCS group that received 20% TUCS six times/day in addition to the conventional treatment of CED and (2) the control group, which was prescribed artificial tears as placebo in addition to the conventional treatment of CED. The rate of healing of CEDs was measured via two maximum linear dimensions perpendicular to each other at the start of therapy and on postoperative days 1–5, 7, and 12.ResultsOf 80 eyes, 40 were assigned to each treatment group. The mean times to complete CED healing were 2.4 0.7 and 3.8 2.1 days in the TUCS and control groups, respectively (P 0.001). Persistent CED occurred in two eyes in the control group but in no eyes in the TUCS group.ConclusionTUCS therapy may be safe and effective in healing CEDs after vitrectomy in patients with diabetes.

Tenonplasty Combined With Amniotic Membrane Transplantation for Patients With Severe Ocular Burns Induced Anterior Segment Necrosis.

This article describes a novel surgical technique for successful repair of intractable corneoscleral necrosis caused by severe ocular burns. In this prospective case series, 19 eyes of 15 consecutive patients with sectional scleral necrosis and persistent corneal epithelial defects were treated with tenonplasty and amniotic membrane transplantation. The main outcome measure was the stability of the ocular surface after reepithelialization and repair of defects. All patients underwent successful combined surgery involving tenonplasty and amniotic membrane transplantation, in which the conjunctival and corneal surfaces were reconstructed. The interval from injury to surgery was 37.4 ± 24.5 days (3–91 days), and the ocular surfaces became stabilized in 82.2 ± 35.4 days (26–156 days, median 87 days). At the final visit, all cases presented with corneal opacity and neovascularization to various degrees. The best-corrected visual acuity decreased from 2.83 ± 1.02 LogMAR preoperatively to 2.87 ± 1.31 LogMAR postoperatively. The results imply that tenonplasty combined with amniotic membrane transplantation could provide vascular supply to the ischemic sclera, repair defects in the conjunctiva, and promote corneal reepithelialization, thus facilitating ocular surface stabilization after burns.

The Use of Autologous Serum to Reverse Severe Contact Lens-induced Limbal Stem Cell Deficiency.

To describe the efficacy of autologous serum (AS) eye drops to reverse severe contact lens (CL)-induced limbal stem cell (LSC) deficiency (LSCD). This is a prospective, uncontrolled, interventional case series that enrolled 20 eyes of 14 consecutive patients diagnosed with severe CL-induced LSCD at presentation, based on clinical examination, at a tertiary referral center for the period December 2016 to December 2018. All eyes underwent AS treatment for at least 2 weeks with a follow-up for at least 2 months. Demographic data and treatment outcomes were collected and analyzed. The mean patient age at presentation was 30.5 years (range, 19-49 years). The mean duration of soft contact lens wear was 15.6 years (SD, 7.58 years; range, 5-31 years). All study eyes had pain and blurred vision at presentation. All eyes had recurrent or persistent corneal epithelial defect, stromal scarring and opacity, and superficial vascularization and peripheral pannus at presentation. Aggressive treatment with AS succeeded in all eyes. Signs and symptoms of LSCD stabilized in all eyes within 2 weeks and resolved in 6 eyes (30.0%) in 2 weeks, 9 eyes (45.0%) in 4 weeks, and 5 eyes (25.0%) in 8 weeks. The mean follow-up time was 9.45 ± 1.79 weeks (range, 8-24 weeks). Early identification and aggressive treatment of the ocular surface disease with AS can medically reverse severe CL-induced LSCD and prevent the need for surgical intervention.

Modern biotechnological treatment methods of persistent corneal epithelial defects

The article reviews modern methods of treatment of persistent corneal epithelial defects and considers the factors involved in the development of this pathology, including the limbal stem cell deficiency, which is likely to play the main role. The most promising treatment methods are described, particularly the use of blood derivatives and cell therapy.

Tissue-Cultured Human Cord Lining Epithelial Cells in Treatment of Persistent Corneal Epithelial Defect.

BACKGROUND:Persistent corneal epithelial defect (PED) is a consequence of many ocular surface disorders. Although many therapies have been suggested, the treatment of this disease have faced a lot of difficulties up to now. The transplatation of cultivated amniotic epithelial cells sheets is the new promised method for PED. Cord lining epithelial cells (CLECs) are epithelial cells of amniotic membrane of umbilical cord, so these cultivated cells sheet may be good for treating PEDAIM:To evaluate the efficacy of the transplantation of cultivated CLECs sheets in treatment of PED and analyze some influential factors of this therapy.METHODS:A prospective interventional case series with transplantation of tissue-cultured human CLECs in 37 PED eyes in Vietnam National Institute of Ophthalmology.RESULTS:Thirty four of 37 eyes were healed with the cells transplantation and 22 eyes of them healed within a week postoperatively. There were normal corneal scars and normal corneal epithelial cell (by impression cytology detection) on transplantation site in all 31 successful cases. The other successful eyes were done lamellar keratoplasty (respectively in 1 month, 3 months, 6 months and 27 months postoperatively) to investigate the histopathology of the CLECs transplant site. The histopathological images showed normal corneal scar and there was no appearance of CLECs in transplant site.CONCLUSION:tissue-cultured human CLECs transplantation is a quite safe and effective treatment for persistent corneal epithelial defect. The CLECs may help the epithelial healing at early stage but do not exist at transplant site for a long time.

Surgical treatment of keratoglobus: key techniques of bridge-shaped flap penetrating keratoplasty and whole lamellar keratoplasty with corneoscleral limbal

Objective: Introduce the surgical techniques of bridge-shaped flap penetrating keratoplasty and whole lamellar keratoplasty with corneoscleral limbal and the comparison of therapeutic effects on keratoglobus. Methods: Five patients (eight eyes) with keratoglobus from January 2010 to December 2015 were included. Three eyes received bridge-shaped flap penetrating keratoplasty (two eyes with corneal penetrating injury due to trauma, one eye with descemet's membrane detachment) and five eyes received whole lamellar keratoplasty with corneoscleral limbal. Results: The patients (four male, one female) aged 3 to 67 years old. Three younger patients were complicated with blue sclera. The visual acuity of all the patients pre-operation were lower than 0.05. The average visual acuity after whole lamellar keratoplasty (LKP) surgery was 0.2, while the average visual acuity after bridge-shaped flap penetrating keratoplasty (PKP) was 0.5. The corneal epithelium of the three eyes received bridge-shaped flap PKP surgery was completely healed within a week with no recurrence of corneal epithelial defect. Whereas one eye after whole LKP surgery arised persistent corneal epithelial defect and healed after blepharorrhaphy. The corneal epithelial of another eye after whole LKP surgery healed slowly and was completely healed after wearing a bandage lens on corneal for 2 months. The corneal epithelial of the remaining three eyes after whole LKP surgery was completely healed within a week. Two eyes received bridge-shaped flap PKP surgery arised corneal graft rejection 2 months after operation and recovered after anti-rejection treatment. No corneal graft rejection arised in the patients receiving whole LKP surgery. Conclusions: The whole lamellar keratoplasty with corneoscleral limbal could effectively reinforce corneal, avoid corneal penetrating injury caused by minor trauma, and improve visual acuity in keratoglobus whose corneas were gradually thinning and corrected vision cannot be improved. The patients with corneal perforating injury or descemet's membrane detachment could obtain good visual prognosis receiving bridge-shaped flap penetrating keratoplasty. (Chin J Ophthalmol, 2019, 55:916-922).

Case report: persistent corneal epithelial defect after glaucoma device implantation for radiation glacoma

AbstractPurposeWe report a case with persistent epithelial defect after Barvert glaucoma implant for radiation glaucoma.Methods and Results62‐year‐old man had a total of 70 Gray radiation exposure for 2 months for left ethmoid sinus cancer In December 2015. In February 2016, the patient visited eye clinic for left eye pain. Only SPK was found and artificial tear drop was prescribed and followed‐up in the clinic. In January 2017, left intraocular pressure was elevated and angle neovascularization was found. Photocoagulation was started on diagnosis of radiation glaucoma. Although the treatment could not be completed due to progression of cataract, intraocular pressure had been within normal range under glaucoma drops treatment. He was referred to our hospital in August 2018 for the treatment of cataract surgery in his left eye. At the first visit, his left best corrected visual acuity was 0.01 and left Intraocular pressure was 20 mmHg. Mild Superficial punctate keratitis was found in his left eye but tear fluid meniscus was normal. We planned to add PC after cataract surgery at first. But in consideration of the possibility of deterioration of Neovasucular Glaucoma after surgery, we performed not only cataract surgery but also vitrectomy with Barvert glaucoma implantation and photocoagulation in September of the same year. Postoperative inflammation was transient, the intraocular pressure was good, and small corneal erosion was found immediately after the operation. However, after surgery, there was an extreme decrease in lacrimal secretion, and corneal erosions were enlarged, resulting in persistent epithelial defects. Treatment with a punctum plug, a therapeutic soft contact lens, eye drops etc. was poorly improved, and a corneal infiltration suspected of fungal keratitis was found during the course.ConclusionsImplantation or vitreous surgery for radiation retinopathy or radiation glaucoma may cause persistent corneal epithelial defects. It is necessary to carefully check the preoperative evaluation of tears and corneal condition and to carry out minimally invasive treatment.

Blood derived treatment from two allogeneic sources for severe dry eye associated to keratopathy: a multicentre randomised cross over clinical trial

AimTo compare the efficacy of cord blood and peripheral adult donor blood serum eyedrops, controlled for growth factor content, in the treatment of severe dry eye diseases (DED) resistant to...

Autologous Serum-Based Eye Drops for Treatment of Ocular Surface Disease: A Report by the American Academy of Ophthalmology

To describe the safety and effectiveness of using autologous serum-based eye drops for the treatment of severe dry eye and persistent corneal epithelial defect. Literature searches of the PubMed and Cochrane Library databases were conducted most recently in March 2019. The searches identified 281 citations, which were reviewed in abstract form. Of these, 48 were selected for a full-text review, and 13 met the inclusion criteria and were assigned a quality-of-evidence rating by the panel methodologist. Eight of these studies were rated level II and 5 were rated level III; there were no level I studies. This analysis included 10 studies of the use of autologous serum-based eye drops for severe dry eye disease and 4 studies of persistent epithelial defect. Several studies showed good effectiveness, with some improvement in symptoms, signs, or both. Eight of the studies reported improved symptoms for severe dry eye disease, and all noted improvement in at least 1 clinical sign. For persistent epithelial defects, all of the studies showed improvement, with 3 of the 4 demonstrating an improvement rate of more than 90%. Adverse events were rare. Although autologous serum-based tears may be effective in the treatment of severe dry eyeand persistent epithelial defect, conclusions are limited owing to the absence of controlled trials.

NEXAGON for the Treatment of Corneal Persistent Epithelial Defects Following Severe Ocular Chemical and/or Thermal Injuries

NEXAGON for the Treatment of Corneal Persistent Epithelial Defects Following Severe Ocular Chemical and/or Thermal Injuries

Autologous Platelet-rich Plasma Eye Drops Accelerate Re-epithelialization of Post-keratoplasty Persistent Corneal Epithelial Defects.

Purpose:To investigate whether autologous platelet-rich plasma (PRP) eye drops accelerate re-epithelialization of post-keratoplasty persistent corneal epithelial defects (PEDs).Methods:A total of 34 eyes with PEDs after keratoplasty (24 penetrating keratoplasty and 10 deep anterior lamellar keratoplasty) that were refractory to conventional medical treatments were treated with PRP eye drops every 3 hours. PRP eye drops were prepared with a low- and high-speed centrifugation method and final platelet counts were 700,000-800,000 plt/μl. The mean treatment duration for complete re-epithelialization was compared with the mean treatment duration of conventionally treated corneal defects before the PRP treatment by paired t-test. The mean treatment duration was also statistically analyzed between age groups, gender, indications for keratoplasty, and types of keratoplasty using analysis of variance (ANOVA).Results:Treatment with autologous PRP eye drops led to rapid re-epithelialization in all eyes. The mean treatment duration for complete re-epithelialization was 2.47 ± 1.21 weeks, which was significantly shorter than the mean treatment duration of conventionally treated corneal defects before PRP treatment (6.82 ± 1.24 weeks) (P = 0.0001). There was no significant correlation between re-epithelialization time and patients' age, sex, indications for keratoplasty, and techniques of corneal transplantation.Conclusion:Treatment with autologous PRP eye drops is an effective and reliable approach that accelerates re-epithelialization of post-transplantation PEDs.

Ophthalmological perspectives of toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN) is as rare as two cases per million per year, but the ocular manifestations and sequelae are very severe. We present a case series of seven patients admitted to the intensive care unit in a tertiary hospital with a diagnosis of TEN describing the extent of ocular involvement, its response to treatment, and appearance of sequelae. All seven were drug-induced with moderate-to-severe skin, mucosal, ophthalmic involvement, and systemic involvement. Ocular findings on presentation were eyelid skin detachment, adherent lid margins, bilateral mucopurulent conjunctivitis with inflammatory membranes, and punctate epithelial keratitis in all patients. Large persistent corneal epithelial defect was seen in four patients. On follow-up, five had severe keratoconjunctivitis sicca and entropion with trichiasis. Photophobia was the major debilitating sequelae. Early management was the key to reduce severity, cicatrization, and sequelae. Corticosteroids topically and systemically, topical cyclosporine, and lubricants were the mainstay of management.

Clinical picture and diagnosis of neurotrophic keratopathy

Neurotrophic keratopathy is characterized by corneal surface alterations, persistent corneal epithelial defects and/or corneal ulcerations associated with corneal sensory abnormalities. Due to the variable clinical picture neurotrophic keratopathy is often overlooked or diagnosed too late in the course of the disease. Discussion of the clinical picture of neurotrophic keratopathy and recommendations for correct diagnosis. Analysis of the existing literature and discussion of basic recent publications. Neurotrophic keratopathy is defined as adisease related to alterations in corneal nerves leading to impairment in sensory and trophic function with consequent breakdown of the corneal epithelium affecting health and integrity of the tear film, epithelium and stroma. It can occur with infections, autoimmune diseases, after trauma or ocular surgery, with intracranial neoplasia, in systemic diseases and genetic syndromes. It is classified into three stages: mild (epithelial changes without epithelial defects), moderate (epithelial defects) and severe (stromal involvement). The clinical hallmark is reduced or absent corneal sensation. Therefore, corneal sensitivity testing is essential in the diagnosis of neurotrophic keratopathy along with the patient history, clinical examination and diagnostic tests, such as vital stains and, if possible, in vivo confocal microscopy. The correct diagnosis and classification of neurotrophic keratopathy enable astage-adapted step-ladder therapeutic approach with subsequent reduction of progression and complications of the disease.

"Therapeutic Penetrating Keratoplasty: A Retrospective Review".

To report the indications, outcomes, and complications of therapeutic penetrating keratoplasty (Th PK) in patients with corneal perforation and/or nonhealing corneal ulceration. A retrospective review was conducted of 51 eyes of 51 patients undergoing Th PK between January 1, 2006 and April 15, 2016. Data collected included patient demographics, visual acuity (VA), size of the corneal infiltrate and epithelial defect, degree of corneal thinning/perforation, microbiological results, surgical details, and postoperative complications. The average age at presentation was 56.0 years (range 6-92 years), and most of the patients were females (n=31, 60.8%). Th PK was performed for corneal perforation in 28 eyes (54.9% of cases), nonhealing corneal ulcer in 16 eyes (31.4% of cases), and imminent risk of corneal perforation in 7 eyes (13.7% of cases). Infection was the most common reason for performing a Th PK and was present in 92.3% (47/51) of all cases. Of the infectious cases, the most common etiologies were bacterial (44.7%, 21/47) and fungal (31.9%, 15/47). The most common identifiable risk factor for undergoing a Th PK was a history of contact lens wear, which was seen in 32.7% of patients. Initial anatomic success was achieved in all patients after performing Th PK. Most patients (33/51; 64.7%) had clear grafts at their last follow-up examination. There was an improvement in VA in 70.2% (33/47, where data were available) of the patients at the final postoperative visit compared with the preoperative visit. Average best postoperative VA (1.14±0.88 logarithm of the minimum angle of resolution [LogMAR]; 20/276) was significantly better than the presenting (1.98±0.68 LogMAR; 20/1910) and preoperative (2.18±0.55 LogMAR; 20/3,027) visual acuities (P<0.0001). The most common complication after Th PK was cataract, which was present in 81.8% (27/33) of phakic eyes in which lens status could be assessed, followed by graft failure (47.1%; 24/51), and secondary glaucoma (45.1%; 23/51). Five eyes developed infection in the therapeutic graft, four eyes had persistent corneal epithelial defect at their last follow-up visit, and two eyes underwent evisceration. Therapeutic penetrating keratoplasty achieves anatomic success and it is a useful procedure for restoring a stable cornea in cases in which infection fails to heal or when the cornea perforates. Furthermore, Th PK achieves corneal clarity and improves vision in most patients.

Topical Treatment of Persistent Epithelial Defects with a Matrix Regenerating Agent.

The aim of the study was to assess the efficacy of a topical regenerating agent (RGTA) for management of persistent epithelial defects (PEDs) resistant to conventional therapy. Twenty-one patients (23 eyes) with PEDs despite the use of conventional therapy for lagophthalmos (n = 4), neurotrophic ulcer (n = 9), chemical burn (n = 3), Stevens-Johnson syndrome (n = 1), atopic keratoconjunctivitis (n = 1), severe dry eye (n = 2), peripheral ulcerative keratitis (n = 1), fungal keratitis (n = 1), and bacterial keratitis (n = 1) were enrolled in the study. Patients were treated with RGTA (Cacicol; Thea, Paris, France) instilled at a dosage of one drop on alternate days. Patients were evaluated by slit-lamp examination, anterior segment photography, and fluorescein-dye testing. Ulcer areas were noted on alternate days starting from the first day of instillation. Twenty of 23 eyes (86.9%) displayed complete corneal healing after a mean period of ∼7.2 days (range, 2-20 days). Mean decrease ratio of ulcer area observed was 61.2% (range, 8.8%-100%, n = 19) on the 2nd day, 74.4% (range, 36%-100%, n = 16) on the 4th day, 80.2% (range, 43.7%-100%, n = 12) on the 6th day, 88.5% (range, 55.9%-100%, n = 9) on the 8th day, and 85.5% (range, 58.3%-100%, n = 7) on the 10th day. No significant differences were found in the epithelialization speed between eyes with and without bandage contact lenses in any postoperative day (P > 0.05). There were no treatment-related local or systemic side effects during the study. RGTA seems to be an effective therapeutic alternative in the treatment of persistent corneal epithelial defects.