Treatment Of Persistent Epithelial Defects Research Articles

Prevention and Treatment of Persistent Epithelial Defects After Common Refractive Surgery Procedures.

To discuss the prevention and treatment of persistent epithelial defects after the most common refractive surgeries-photorefractive keratectomy, laser in situ keratomileusis, or small incision lenticule extraction. PubMed was used to search the medical literature. Persistent epithelial defects are infrequent after photorefractive keratectomy, laser in situ keratomileusis, or small incision lenticule extraction. In the authors' opinion, any persistent epithelial defect present at 1 week or beyond after surgery should be treated aggressively with a properly fit bandage contact lens, lubrication with non-preserved artificial tears, and treatment of any eyelid abnormalities, including nocturnal lagophthalmos. Consideration should be given for presumptive treatment for herpes simplex virus or varicella zoster virus infection. If the persistent epithelial defect does not close within 2 weeks, then other measures should be considered, such as autologous serum drops, topical losartan, amniotic membranes, and topical human recombinant nerve growth factor to limit corneal scarring fibrosis and microbial infection. Persistent epithelial defects are among the most feared complications of refractive surgery. Timely and aggressive treatment should be instituted to close the epithelium prior to the development of scarring fibrosis and/or microbial corneal infection. [J Refract Surg. 2024;40(2):e117-e124.].

The platelet-rich plasma lysate use in the treatment of persistent epithelial defects after keratoplasty

AIM:to evaluate the effectiveness of the platelet-rich plasma lysate (PRP lysate) use in the treatment of persistent epithelial defects (PED) after keratoplasty.
 MATERIALS AND METHODS:In the study, 60 patients with PED after keratoplasty were included. The 1st group (24 cases)included patients after keratoplasty with low risk of rejection, and the 2nd group 36 cases after keratoplasty with highrisk of rejection. Each group was divided into two subgroupscontrol subgroups 1a (cases 10) and 2a (cases 16), where patients received only standard postoperative therapy, and the main subgroups 1b (cases 14) and 2b (cases 20), in which PRP lysate was prescribed against the background of standard therapy, starting from the Day 15 post-op. As the criterion for effective treatment, complete persistent epithelialization after keratoplasty was considered.
 RESULTS:The effectiveness of the use of PRP lysate in the subgroup 1b was 85.7%, while complete epithelialization in the control subgroup 1a was recorded in 70%; in the subgroup 2b, complete epithelialization was observed in 55%, in the control subgroup 2ain 43.75%.
 CONCLUSION:The use of PRP lysate in the treatment of PED after corneal transplantation as an adjuvant therapy is effective and safe in both high and low risk keratoplasty. In the examined category of patients, treatment with blood derivatives increases the frequency and rate of complete epithelialization.

Treatment of persistent epithelial defects with single-dose autologous serum eye drops.

We aimed to investigate the efficacy and safety of single-dose autologous serum eye drops (ASEDs) for treatment of persistent corneal epithelial defects (PEDs). About 34 eyes of 26 patients treated from March 2016 to May 2020 with a single dose of ASEDs for PEDs that did not respond to conventional treatment were retrospectively evaluated. Patient demographics, predisposing factors, size, and duration of the PED, duration of treatment, and dosage of ASEDs, PED healing time, success rate of the ASED treatment, and follow-up time after the onset of ASED treatment were recorded. Autologous serum eye drops (20%) were prepared by diluting the serum with preservative-free artificial tears in single-dose vials. Vials were stored at -20°C and used daily after dissolving. The mean patient age was 47.0 ± 18.5 years, and 13 (50%) of the patients were male. The most common indication for ASEDs was PED after keratoplasty. The mean duration of ASED treatment was 8.5 ± 6.3 months, and mean follow-up time was 22.8 ± 12.2 months. Autologous serum eye drop treatment was effective in 25 (73.5%) eyes and partially effective in 5 (14.7%) eyes. None of the eyes displayed complications related to the treatment. In patients with PED for whom conservative treatment is insufficient, ASEDs prepared by dilution with preservative-free artificial tears in single-dose vials and administered based on the daily use principle appear to be effective and safe.

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.

Case series: Extended wear of rigid gas permeable scleral contact lenses for the treatment of persistent corneal epithelial defects

To report the successful treatment of persistent corneal epithelial defects that failed to respond to alternative treatment methods using extended wear of three different rigid gas-permeable scleral lenses. Eight eyes of eight patients with persistent corneal epithelial defects were treated with Blanchard Onefit 2.0 Scleral lens, BostonSight Scleral lens, and BostonSight PROSE device and were observed for defect resolution and improvement in best-corrected visual acuity over the duration of treatment. All eyes observed complete re-epithelialization with a mean time of 11.1 ± 5.5 days. At the conclusion of the treatment, visual acuity improved in all but one patient. No complications were observed during treatment. Scleral lenses provide the corneal epithelium with hydration, oxygen permeation, and protection from mechanical forces; thereby facilitating healing of persistent corneal epithelial defects. This case series demonstrates the successful use of continuous wear scleral lenses in a number of patients for the treatment of persistent epithelial defects refractory to other interventions.

Pathophysiology of Corneal Scarring in Persistent Epithelial Defects After PRK and Other Corneal Injuries.

To analyze corneal persistent epithelial defects that occurred at 3 to 4 weeks after -4.50 diopter (D) photorefractive keratectomy (PRK) in rabbits and apply this pathophysiology to the treatment of persistent epithelial defects that occur after any corneal manipulations or diseases. Two of 168 corneas that had -4.50 D PRK to study epithelial basement membrane regeneration developed spontaneous persistent epithelial defects that did not heal at 3 weeks after PRK. These were studied with slit-lamp photographs, immunohistochemistry for the myofibroblast marker alpha-smooth muscle actin (α-SMA), and transmission electron microscopy. Myofibroblasts developed at the stromal surface within the persistent epithelial defect and for a short distance peripheral to the leading edge of the epithelium. No normal epithelial basement membrane was detectable within the persistent epithelial defect or for up to 0.3 mm behind the leading edge of the epithelium, although epithelial basement membrane had normally regenerated in other areas of the zone ablated by an excimer laser where the epithelium healed promptly. A persistent epithelial defect in the cornea results in the development of myofibroblasts and disordered extracellular matrix produced by these cells that together cause opacity within, and a short distance beyond, the persistent epithelial defect. Clinicians should treat persistent epithelial defects within 10 days of non-closure of the epithelium to facilitate epithelial healing to prevent long-term stromal scarring (fibrosis). [J Refract Surg. 2018;34(1):59-64.].

Amniotic membrane in ophthalmology: properties, preparation, storage and indications for grafting-a review.

The use of amniotic membrane in ophthalmic surgery and other surgical procedures in the fields of dermatology, plastic surgery, genitourinary medicine and otolaryngology is on the increase. Furthermore, amniotic membrane and its epithelial and mesenchymal cells have broad use in regenerative medicine and hold great promise in anticancer treatment. Amniotic membrane is a rich source of biologically active factors and as such, promotes healing and acts as an effective material for wound dressing. Amniotic membrane supports epithelialization and exhibits anti-fibrotic, anti-inflammatory, anti-angiogenic and anti-microbial features. Placentas utilised in the preparation of amniotic membrane are retrieved from donors undergoing elective caesarean section. Maternal blood must undergo serological screening at the time of donation and, in the absence of advanced diagnostic testing techniques, 6months postpartum in order to cover the time window for the potential transmission of communicable diseases. Amniotic membrane is prepared by blunt dissection under strict aseptic conditions, then is typically transferred onto a nitrocellulose paper carrier, usually with the epithelial side up, and cut into multiple pieces of different dimensions. Amniotic membrane can be stored under various conditions, most often cryopreserved in glycerol or dimethyl sulfoxide or their mixture with culture medium or buffers. Other preservation methods include lyophilisation and air-drying. In ophthalmology, amniotic membrane is increasingly used for ocular surface reconstruction, including the treatment of persistent epithelial defects and non-healing corneal ulcers, corneal perforations and descemetoceles, bullous keratopathy, as well as corneal disorders with associated limbal stem cell deficiency, pterygium, conjunctival reconstruction, corneoscleral melts and perforations, and glaucoma surgeries.

Topical Application of a Regenerative Agent for the Treatment of Persistent Epithelial Defects after Penetrating Keratoplasty

Topical Application of a Regenerative Agent for the Treatment of Persistent Epithelial Defects after Penetrating Keratoplasty

Трансэпителиальная фототерапевтическая кератэктомия в лечении персистирующих эпителиальных дефектов кератотрансплантата

Трансэпителиальная фототерапевтическая кератэктомия в лечении персистирующих эпителиальных дефектов кератотрансплантата

Peptide therapies for ocular surface disturbances based on fibronectin-integrin interactions.

The condition of the corneal epithelium is a critical determinant of corneal transparency and clear vision. The corneal epithelium serves as a barrier to protect the eye from external insults, with its smooth surface being essential for its optical properties. Disorders of the corneal epithelium include superficial punctate keratopathy, corneal erosion, and persistent epithelial defects (PEDs). The prompt resolution of these disorders is important for minimization of further damage to the cornea. Currently available treatment modalities for corneal epithelial disorders are based on protection of the ocular surface in order to allow natural healing to proceed. PEDs remain among the most difficult corneal conditions to treat, however. On the basis of characterization of the pathobiology of PEDs at the cell and molecular biological levels, we have strived to develop new modes of treatment for these defects. These treatments rely on two key concepts: provision of a substrate, such as the adhesive glycoprotein fibronectin, for the attachment and migration of corneal epithelial cells, and activation of these cells by biological agents such as the combination of substance P and insulin-like growth factor-1 (IGF-1). Central to both approaches is the role of the fibronectin-integrin system in corneal epithelial wound healing. Determination of the minimum amino acid sequences required for the promotion of corneal epithelial wound closure by fibronectin (PHSRN) and by substance P (FGLM-amide) plus IGF-1 (SSSR) has led to the development of peptide eyedrops for the treatment of PEDs that are free of adverse effects of the parent molecules.

Cultivated oral mucosal epithelial transplantation for persistent epithelial defect in severe ocular surface diseases with acute inflammatory activity.

PurposeTo assess the clinical efficacy of cultivated oral mucosal epithelial transplantation (COMET) for the treatment of persistent epithelial defect (PED).MethodsWe treated 10 eyes of nine patients with PED (Stevens–Johnson syndrome: three eyes; thermal/chemical injury: five eyes; ocular cicatricial pemphigoid: two eyes) with COMET at Kyoto Prefectural University of Medicine, Kyoto, Japan from 2002 to 2008.ResultsPreoperatively, PED existed on over more than 50% of the corneal surface in seven eyes. Severe ocular surface inflammation with fibrovascular tissue surrounded the PED in all 10 eyes. At 24-weeks postoperative, PED had improved in all cases except 1 in which the patient was unable to return to the hospital (95% CI, 55.5–99.7; Wilcoxon signed-rank test, p = 0.0078). The preoperative median of logarithmic minimum angle of resolution was 1.85 (range 0.15–2.70), and 1.85, 1.85, and 1.52 at the 4th, 12th, and 24th postoperative week, respectively. The mean total preoperative ocular surface grading score was 7.0 (range 4–17). At 4 and 12 weeks postoperative, the total ocular surface grading score had improved significantly (p = 0.0020, p = 0.0078), and at 24 weeks postoperative, it was 3.0 (range 2–12, p = 0.0234). During the follow-up period (median 23.3 months, range 5.6–39.7 months), no recurrence of PED was observed in any eye, and long-term ocular surface stability was obtained.ConclusionCOMET enabled complete epithelialization of PED and stabilization of the ocular surface in patients with severe ocular surface disease, thus preventing end-stage cicatrization and vision loss at a later stage.

Open Clinical Study of Eye Drops Containing the Fibronectin-Derived Peptide PHSRN for Treatment of Persistent Corneal Epithelial Defects

We have previously shown that the fibronectin-derived peptide PHSRN (Pro-His-Ser-Arg-Asn) promotes corneal epithelial wound healing in vivo. We have now examined the clinical efficacy of eye drops containing the PHSRN peptide for treatment of persistent epithelial defects (PEDs) of the cornea. Seven patients (5 men and 2 women; mean age±SD, 78.3±9.4 years) with PEDs were treated by administration of eye drops containing PHSRN. The duration of the PEDs before treatment was 7.4±5.5 weeks. The eye drops were administered as 1 drop per eye 4 times a day. Epithelial defects were observed with a slit-lamp microscope and photographed during the treatment course. Epithelial defects in 5 of the 7 affected eyes (71%) responded to PHSRN treatment as manifested by complete epithelial resurfacing within the 4-week period after treatment initiation. The mean±SD time required for complete epithelial resurfacing in the 5 responding subjects was 15.8±3.4 days. No adverse effects of treatment were observed in any of the subjects. Eye drops containing the fibronectin-derived PHSRN peptide are clinically efficacious for the treatment of PEDs.

Effect of autologous platelet-rich plasma on persistent corneal epithelial defect after infectious keratitis

Platelet-rich plasma (PRP) harbors high concentrations of growth factors related to the promotion of wound healing. We evaluated the efficacy of PRP eyedrops in the treatment of persistent epithelial defects (PEDs). Autologous PRP and autologous serum (AS) were prepared from whole blood. The concentrations of transforming growth factor (TGF)-β1, TGF-β2, epidermal growth factor (EGF), vitamin A and fibronectin in the PRP and AS were analyzed and compared. The corneal epithelial healing efficacy of PRP was compared with that of AS in patients with PED induced by post-infectious inflammation. The concentrations of TGF-β1, TGF-β2, EGF, vitamin A and fibronectin in the PRP and AS were not statistically different. However, the concentrations of EGF in the PRP were significantly greater than in the AS. AS was used in 17 and PRP in 11 eyes of 28 patients. The healing rates of the corneal epithelia of the PRP-treated eyes were significantly higher than those treated with AS. The PRP was effective in the treatment of PEDs. This may be attributable to its high concentration of platelet-contained growth factors, most notably EGF. PRP could be an effective, novel treatment option for chronic ocular surface disease.

Combined Application of Autologous Serum Eye Drops and Silicone Hydrogel Lenses for the Treatment of Persistent Epithelial Defects

We investigated the utility of a combination of autologous serum eye drops and a silicone-hydrogel (SH) lens in the treatment of persistent epithelial defects (PEDs). Eight patients who had distinct PED conditions were treated with 50% (v/v) autologous serum eye drops in combination with silicone hydrogel contact lenses and prospectively observed. The pathogenesis of PEDs included Sjogren-type dry eye syndrome, graft-versus-host disease, toxic keratitis, limbal cell deficiency, superior limbic keratoconjunctivitis, and neurotrophic keratitis. The patients had PEDs for 90±81.76 days (range: 30-240 days). Before the initiation of the combined treatment, three patients had already been unsuccessfully treated with SH lenses, and five patients had received serum eye drops alone. The PEDs of the eight eyes healed after a treatment period of 11.8±4.9 days. No visible deposits were noted on the surface of any contact lens. These findings demonstrate that the combination of an SH lens and serum eye drops may be effective in the treatment of intractable PEDs.

Translational Research in Corneal Epithelial Wound Healing

To review both the roles of fibronectin and the sensory neurotransmitter substance P in corneal epithelial wound healing and the clinical application of these agents to treat persistent corneal epithelial defects. Fibronectin is expressed at the site of corneal epithelial defects, serves as a provisional matrix for the migration of epithelial cells, and stimulates epithelial wound healing in vitro and in animal models. Eyedrops containing autologous plasma fibronectin are also effective for the treatment of persistent epithelial defects of the cornea in patients. Substance P and insulin-like growth factor-1 synergistically stimulate corneal epithelial wound healing in vitro and in animal models. Furthermore, the administration of eyedrops containing both a substance P-derived peptide (FGLM-amide) and insulin-like growth factor-1-derived peptide (SSSR) is effective for the treatment of persistent epithelial defects in individuals with neurotrophic keratopathy. Basic research on the mechanism of corneal epithelial wound healing has the potential to lead to the development of new modes of treatment for persistent corneal epithelial defects. Clinical experience with eyedrops containing fibronectin or both FGLM-amide and SSSR has highlighted the importance of the basement membrane and neural stimuli in maintenance of the integrity of the normal corneal epithelium.

Plasma Rich in Growth Factors as a Therapeutic Agent for Persistent Corneal Epithelial Defects

To evaluate the efficacy of topically applied autologous plasma rich in growth factors (PRGF) as a treatment for persistent epithelial defects (PEDs) of the cornea. A series of prospective noncomparative cases. Twenty eyes from 18 patients with PED with various underlying etiopathologies: neurogenic, iatrogenic, associated with burning or secondary to severe dry eye. Patients were treated with a PRGF eyedrop solution. Serial photographs of the cornea were taken until epithelialization was complete. We had previously characterized the levels of a panel of growth factors (platelet-derived growth factor, epithelial growth factor, vascular endothelial growth factor, hepatocyte growth factor, fibroblast growth factor, and nerve growth factor) in the PRGF of 11 of these patients. The following variables were additionally recorded: (1) duration of PED before treatment, (2) previous treatments, (3) time for complete epithelialization, and (4) treatments required concomitantly with PRGF. Epithelial defects healed in 17 of 20 cases (85%), with a mean therapeutic time of 10.9 weeks (range 2-39 weeks). Mean progression time before treatment was 26.7 weeks (range 2-104 weeks). Growth factor concentrations were platelet-derived growth factor 12645.9 +/- 1690.0 pg/mL, epithelial growth factor 468.9 +/- 97.6 pg/mL, vascular endothelial growth factor 204.5 +/- 119.4 pg/mL, hepatocyte growth factor 149.5 +/- 173.5 pg/mL, fibroblast growth factor 82.6 +/- 95.9 pg/mL, and nerve growth factor 37.7 +/- 18.6 pg/mL. PRGF, when applied as eyedrops, is a highly effective therapeutic agent for the treatment of a broad etiopathological spectrum of corneal PEDs.

The use of contact lenses in the treatment of persistent epithelial defects

The types and applications of bandage contact lenses are varied and diverse. This article provides a summary of the corneal pathologies that will predispose patients to persistent epithelial defects (PEDs) along with an overview of the types of contact lenses that can be utilised to treat these conditions.

Persistent Epithelial Defects Due to Neurotrophic Keratopathy Treated with a Substance P-Derived Peptide and Insulin-Like Growth Factor 1

The loss of corneal sensation results in the development of persistent corneal epithelial defects. The combination of a substance P-derived peptide, phenylalanine -glycine-leucine-methionine (FGLM)-amide, and insulin-like growth factor 1 (IGF-1) stimulates corneal epithelial migration in vitro and corneal epithelial wound closure in vivo. The clinical efficacy of eye drops containing FGLM-amide and IGF-1 for the treatment of persistent epithelial defects in individuals with neurotrophic keratopathy was examined in a prospective open study. Eleven patients with persistent corneal epithelial defects associated with neurotrophic keratopathy were treated for up to 28 days by the administration of eye drops containing FGLM-amide and IGF-1. The course of epithelial healing was monitored by slit-lamp examination, and visual acuity was measured before and after treatment. Complete epithelial resurfacing was achieved in eight of the nine (89%) cases of persistent epithelial defects in the nine patients who received the full course of treatment. Epithelial defects had completely resurfaced in two of nine (22%) and five of nine (56%) cases within 1 and 2 weeks, respectively, after treatment initiation. No adverse effects of treatment were observed in any of the 11 patients. Eye drops containing FGLM-amide and IGF-1 induced the rapid resurfacing of persistent epithelial defects in individuals with neurotrophic keratopathy.

Combination of serum eye drops with hydrogel bandage contact lenses in the treatment of persistent epithelial defects

The treatment of persistent epithelial defects (PED) with autologous serum eye drops is often combined with conventional medication such as artificial tears and topical antibiotics, but until now no report exists on the use of a bandage contact lens (BCL) in combination with autologous serum eye drops in the treatment of PEDs. We report six eyes (five patients) which were all treated with autologous serum eye drops in combination with an FDA group IV hydrogel contact lens. Five patients aged 36-88 years, were suffering from six PEDs for 73.5+/-46.9 days due to rheumatoid sterile corneal ulcer (n=1), neurotrophic keratopathy (n=3) or partial limbal stem cell deficiency (n=1). All patients had been unsuccessfully treated with conventional therapy before. Three of them had already had an amniotic membrane transplantation and two had undergone a keratoplasty; however, the epithelial defect persisted or recurred. In all cases, an FDA group IV hydrogel contact lens (Biomedics 55, ocufilcon D, 55% water content) was fitted and serum eye drops applied 8 times a day. The PED healed in five of six eyes after a treatment period of 14.2+/-8.9 days. In one eye the PED became smaller, but it took 90 days until the lesion healed completely. In three eyes (two patients) white deposits appeared on the surface of the BCL during the treatment after 12.3+/-5.1 days. Because no signs of inflammation were observed and since the epithelial defect improved, a new identical lens was applied and the medication continued unaltered. The surface of contaminated and non-contaminated BCLs were analyzed by scanning electron microscopy and SDS gel-electrophoresis. The scanning electron microscopic examination presented a coating of amorphous material with a wrinkled appearance and many corpuscular deposits. There was no indication of bacterial colonisation. The SDS gel-electrophoresis showed a small band at 65 kDa, probably albumin. These findings suggest that the combination of a therapeutic contact lens and serum eye drops can be successfully used in the treatment of persistent epithelial defects. Deposition of albumin may occur on the surface of the contact lenses, which, in the small group presented here, caused no unwanted effects.

Therapeutic Effect of Umbilical Cord Serum Eyedrops for Persistent Corneal Epithelial Defect

To evaluate the therapeutic effect of umbilical cord serum in the treatment of persistent epithelial defect of the cornea. Fourteen eyes of 14 patients with persistent epithelial defect that had persisted for at least 2 weeks despite conventional treatment were treated with 20% umbilical cord serum eyedrops six times a day. The images of the epithelial defects were captured using a camera attached to a slit lamp biomicroscope and the areas of the epithelial defects were calculated. Treatment was considered effective for epithelial defect healing within 2 weeks, partially effective for healing within 2 to 4 weeks, and ineffective for healing requiring either more than 1 month or additional measures. Mean duration of epithelial defect before treatment was 7.2 +/- 6.3 weeks, and mean area was 7.86 +/- 7.32 mm2. Umbilical cord serum therapy was effective in 6 eyes (42.9%), partially effective in 6 (42.9%), and ineffective in 2 (14.2%). Nevertheless, the epithelial defects in both the ineffective eyes were eventually healed within 8 weeks. Mean healing time in effective or partially effective cases was 2.75 +/- 1.06 weeks. The use of umbilical cord serum eyedrops for the treatment of persistent epithelial defect is effective.