Chronic Corneal Epithelial Defects Research Articles

Heat-shock protein expression in canine corneal wound healing.

Heat-shock proteins, particularly the 70-kDa member (Hsp70), have been implicated in facilitating wound healing in multiple tissues. Expression and localization of three HSPs were assessed in normal and wounded canine corneas to elucidate a role in epithelial healing. Paraffin-embedded normal corneas, acute and repeatedly abraded corneas, and keratectomies of spontaneous chronic corneal epithelial defects (SCCEDs) were subjected to routine immunohistochemistry for Hsp27, 47, and 70 expression. Ex vivo corneal defects were created and treated with anti-HSPs or IgG controls, and wound healing was monitored. Primary cultures of canine corneal stromal fibroblasts and corneal epithelial cells were treated with exogenous Hsp70, and an artificial wound was created invitro to monitor restoration of the monolayer. Normal canine corneas exhibited constitutive expression of all HSPs evaluated. Inducible expression was demonstrated in acutely wounded tissues, and expression in the chronically abraded corneas was relocalized. All HSP expression was below the limits of detection in the epithelium of SCCED samples. Inhibition of HSPs in culture resulted in delayed wound healing when compared to controls. Hsp70-treated fibroblasts demonstrated significantly (P<0.001) increased migration and proliferation compared to the vehicle control; however, there was no significant effect of exogenous Hsp70 on corneal epithelial cells. These findings suggest that HSPs are induced in the normal canine cornea during re-epithelialization. Hsp70 expression is likely important for inducing the cytoarchitectural remodeling, migration, and proliferation necessary early in the canine corneal healing response, and suppressed expression may contribute to the pathophysiology of nonhealing defects.

Use of bandage contact lenses for treatment of spontaneous chronic corneal epithelial defects in dogs.

To determine whether polyxylon bandage contact lenses influence healing time and ocular comfort in the management of spontaneous chronic corneal epithelial defects in dogs. Twenty dogs with spontaneous chronic corneal epithelial defects were included. All dogs were treated by debridement under topical anaesthesia at the first presentation. Ten dogs were assigned to the study group (application of a polyxylon bandage contact lens), and the remaining ten served as a control group. The healing time and ocular (dis)comfort were evaluated by assessment of the clinical findings and an owner-based questionnaire. All dogs received the same topical and systemic medication. Healing time for dogs in the study population was significantly shorter (mean 14±0 days) than for dogs in the control group (mean 36±17 days; P=0·005). The spontaneous chronic corneal epithelial defects had completely healed at the first recheck in all dogs with a polyxylon bandage contact lens. The duration of blepharospasm following debridement was significantly shorter in the study population (mean 4±4 days) than in the control group (mean 30±20 days; P=0·001). The use of polyxylon bandage contact lenses is beneficial in the management of spontaneous chronic corneal epithelial defects.

Effect of corneal contact lens wear on healing time and comfort post LGK for treatment of SCCEDs in boxers.

To determine whether dogs with spontaneous chronic corneal epithelial defects (SCCEDs) would heal faster and with an improved comfort score following linear grid keratotomy (LGK) combined with corneal contact lens (Acrivet(™) ) wear when compared to dogs having the LGK procedure alone. Prospective study. Twenty-seven boxer dogs (27 eyes) diagnosed with a SCCEDs were enrolled in the study. A LGK was performed on all dogs under dexmedetomidine and butorphanol sedation. Fourteen eyes were randomly assigned to receive a corneal contact lens. The dogs were evaluated typically at 7, 10, and 14 days or until the ulceration was healed. Client surveys were completed by the owners to subjectively assess comfort level and contact lens retention. Statistical analyses were performed utilizing generalized linear models and survival analysis with the Wilcoxon-Gehan test to evaluate group differences. All ulcers healed after the LGK procedure. Dogs with bandage contact lenses had a statistically significant (P = 0.035) decrease in median healing time (7 days (95% CI [7,9]) compared to those without contact lenses (10 days (95% CI [7,12])). There was no difference in subjective comfort score between treatment groups. Early contact loss occurred in 28.6% (95% CI [8.4%, 58.1%]) of dogs. All of the Acrivet(™) ruler corneal measurements agreed to within 1 mm (95% CI [87.2%, 100%]) of the Jameson caliper measurements of horizontal corneal diameter. The use of corneal bandage contact lenses significantly decreased median healing time although there was no effect on subjective comfort score. The Acrivet(™) ruler measurements were accurate in determining corneal diameter and therefore contact lens size.

Histopathological features of equine superficial, nonhealing, corneal ulcers.

To evaluate corneal changes associated with chronic, nonhealing, superficial, corneal ulcers in horses via common histopathological stains. Retrospective study. Twenty-four horses diagnosed with chronic, nonhealing, superficial, corneal ulceration. The medical records of horses evaluated at North Carolina State University's Veterinary Teaching Hospital (NCSU-VTH) from 2005 to 2011, diagnosed with a chronic, nonhealing, superficial, corneal ulcer and treated with superficial keratectomy (SK) were reviewed. Inclusion criteria were superficial corneal ulceration, no cellular infiltration via slit-lamp biomicroscopy, no microorganisms evident on corneal cytology, and acquisition of samples for aerobic bacterial and common fungal cultures. Corneal tissue samples were evaluated histopathologically for the presence or absence of a nonadherent epithelial 'lip', epithelial dysmaturity, intraepithelial inflammatory cells, an acellular hyaline zone in the anterior stroma, and stromal inflammatory cells, fibrosis and vascularization. In the majority of analyzed samples, epithelial cells adjacent to the ulcerated site showed nonadherence to the basement membrane and dysmaturity. Intraepithelial inflammatory cell infiltration was uncommon. Histopathological features of an anterior stromal hyaline zone, intrastromal inflammation, fibrosis and vascularization were variably present. The most consistent histopathological characteristics of equine chronic, nonhealing, superficial, corneal ulcers include epithelial nonadherence, epithelial dysmaturity and mild to moderate stromal inflammation; however, one set of histopathological characteristics does not definitively define this syndrome in horses. Additionally, the anterior stromal acellular hyaline zone commonly cited in canine spontaneous chronic corneal epithelial defects (SCCED) is not a consistent finding in equine corneas.

Management of spontaneous chronic corneal epithelial defects (SCCEDs) in dogs with diamond burr debridement and placement of a bandage contact lens

Objective To describe the outcome of canine spontaneous chronic corneal epithelial defects (SCCED) treated with diamond burr debridement (DBD) and bandage contact lens placement (BCL). Animal studied Forty eyes of 36 dogs presenting to a single private practice. Procedures A retrospective review of medical records was performed. Cases were eligible for inclusion if they were newly diagnosed with SCCED by a veterinary ophthalmologist and treated with DBD/BCL. All patients received a complete ocular examination followed by DBD using a battery-powered, handheld motorized burr (Algerbrush(®) , Alger Equipment Company, Lago Vista, TX, USA). A BCL was placed post-debridement in all patients. Data were analyzed for sex, age, breed, duration of clinical signs prior to DBD; number of debridements required before healing was achieved; contact lens retention, complications attributed to DBD, and additional surgical interventions were required to achieve healing. Results The median time to first recheck examination was 7 days (IQR 7-9 days) with 28/40 (70%) of cases healed at this examination. The mean time to second recheck examination was 15.5 ± 5.5 days with 37/40 (92.5%) healed by this examination. The median time to final recheck examination was 19 days (IQR 18-35.5 days) with a range of 18-52 days. All cases resolved by the third and final recheck examination. A second DBD/BCL was performed in 5/40 (12.5%) of cases. The BCL retention rate was 95% over all examination time points. No case required a keratectomy or other surgical intervention to achieve healing. The only complication observed was one case of suspected bacterial keratitis post-DBD/BCL. Conclusions Results suggest that DBD/BCL is safe and effective for treatment of canine SCCED.

Histologic evaluation of the immediate effects of diamond burr debridement in experimental superficial corneal wounds in dogs

To evaluate the corneal changes immediately after diamond burr debridement of superficial corneal wounds in dogs. Spontaneous chronic corneal epithelial defects (SCCEDs) are the most common form of canine recurrent corneal ulcers. The diamond burr has been used in the management of corneal lesions in humans since 1983. Recently, it has been successfully used in the treatment of SCCEDs in dogs; however, little has been documented as to its mechanism of action. Five adult female research dogs euthanized for reasons unrelated to the study were included, providing 10 normal eyes. An excimer laser spatula was used for epithelial removal after delineation with an 8 mm punch biopsy trephine. Diamond burr debridement was performed for 30 and 45 s in five eyes each (groups 1 and 2 respectively). The procedure was performed on the ventral half of the experimental defect as well as ventral normal cornea, immediately after euthanasia, and prior to enucleation. Samples were processed routinely for histologic evaluation and stained with periodic acid-Schiff. No stromal defects could be identified under light microscopy. In experimental corneal wounds, multi-focal areas remained covered by the epithelial basement membrane (BM) after diamond burr treatment in both groups (group 1 = 48% ± 16SD, group 2 = 26% ± 12SD). Removal of BM on group 2 was significantly higher than group 1 (P < 0.05). CONCLUSIONS : The diamond burr allows a safe method of debridement and does not create defects beyond the epithelial BM in corneal wounds in normal dogs. Evaluation of the diamond burr debridement in cases of SCCEDs is warranted.

Treatment of chronic nonhealing neurotrophic corneal epithelial defects with thymosin β4

Neurotrophic corneal defects are difficult to heal and all too often lead to scarring and vision loss. Medical management is often of limited success. We describe the results of nine patients (ages 37-84) with chronic nonhealing neurotrophic corneal epithelial defects who were treated with thymosin beta 4 (Tbeta4) sterile eye drops for 28 or 49 days with a follow-up period of 30 days. Those with geographic defects (six patients) showed dramatic healing without clinically significant neovascularization. Stromal thinning was observed in one patient. Three patients with punctate epithelial defects did not have a demonstrable change in their clinical findings. Reduced ocular irritation was reported by all patients soon after treatment initiation. Results from these compassionate use cases indicate that Tbeta4 may provide a novel, topical approach to wound healing in chronic nonhealing neurotrophic corneal ulcers.

Treatment of Chronic Nonhealing Neurotrophic Corneal Epithelial Defects With Thymosin Beta 4

Treatment of Chronic Nonhealing Neurotrophic Corneal Epithelial Defects With Thymosin Beta 4

Expression of Matrix Metalloproteinase 2 and 9 in Experimentally Wounded Canine Corneas and Spontaneous Chronic Corneal Epithelial Defects

To determine matrix metalloproteinase (MMP) 2 and MMP 9 expression in acute and chronic experimentally wounded canine corneas and keratectomy samples from canine patients with spontaneous chronic corneal epithelial defects (SCCEDs). Mechanical debridement was performed unilaterally in 25 healthy dogs for the acute wound study. Twenty-four hours (n = 8), 48 hours (n = 5), 72 hours (n = 3), or 1 week (n = 9) after wounding, the dogs were euthanized. Debridement was performed once weekly for 8 weeks for the chronic study (n = 8). Therapeutic superficial keratectomies (n = 16) were performed on SCCED patients. Gelatin zymography and immunohistochemistry were performed. Acute wounds showed upregulation of MMP 9 at all time points. At 7 days after wounding, values diminished markedly but remained elevated above those of unwounded controls. SCCED and chronic wound samples showed a significant increase in MMP 9 compared with controls but were less than that of acute wounds. There was no significant difference between chronic wounds versus SCCED samples. Fellow control eyes showed significant upregulation of MMP 9 in tandem with wounded eyes. There was no significant difference in values for MMP 2 in wounded corneas or SCCED compared with those of controls. Immunhistochemistry localized MMP 9 to predominantly the epithelium with some staining of keratinocytes and stroma. The dog exhibits similar MMP expression during corneal wound healing to that of other species. The lack of significant difference in MMP expression between SCCED and chronic wounds suggest that MMP 2 and 9 are not involved in the pathophysiology of SCCED and are more likely altered secondary to a chronic epithelial defect.

Efficacy of two chondroitin sulfate ophthalmic solutions in the therapy of spontaneous chronic corneal epithelial defects and ulcerative keratitis associated with bullous keratopathy in dogs

To determine the efficacy of two antimicrobial-chondroitin sulfate ophthalmic solutions in the therapy of spontaneous chronic corneal epithelial defects (SCCED) and ulcerative keratitis associated with bullous keratopathy in dogs. Eighty dogs with SCCED and 14 dogs with ulcerative keratitis associated with bullous keratopathy. Following manual debridement of nonadherent epithelium, dogs were treated topically with a chondroitin sulfate ophthalmic solution containing either tobramycin or ciprofloxacin. Patients were re-evaluated at 2-week intervals for 4 weeks. After 2 weeks of treatment, 53.6% of eyes with SCCED and 17.6% of eyes with ulcerative keratitis associated with bullous keratopathy had healed. After 4 weeks of treatment, 81.0% of eyes with SCCED and 23.5% of eyes with ulcerative keratitis associated with bullous keratopathy had healed. There were no statistically significant differences in healing percentages between the tobramycin-chondroitin sulfate solution treatment groups and the ciprofloxacin-chondroitin sulfate solution treatment groups. Two dogs with SCCED, one treated with the tobramycin-chondroitin sulfate solution and the other treated with the ciprofloxacin-chondroitin sulfate solution, developed sterile corneal stromal abscesses during the study. Topical therapy with an antimicrobial-chondroitin sulfate ophthalmic solution combined with manual debridement of nonadherent epithelium compares favorably with other published medical and surgical therapies for SCCED; however, these compounds are only equivocally more effective than therapy with manual debridement alone. These solutions appear to be ineffective in the treatment of ulcerative keratitis associated with bullous keratopathy. The significance of the two cases of corneal stromal abscessation is unknown at this time and warrants further investigation.

Feline Corneal Disease

The cornea is naturally transparent. Anything that interferes with the cornea's stromal architecture, contributes to blood vessel migration, increases corneal pigmentation, or predisposes to corneal edema, disrupts the corneas transparency and indicates corneal disease. The color, location, and shape and pattern of a corneal lesion can help in determining the underlying cause for the disease. Corneal disease is typically divided into congenital or acquired disorders. Congenital disorders, such as corneal dermoids are rare in cats, whereas acquired corneal disease associated with nonulcerative or ulcerative keratitis is common. Primary ocular disease, such as tear film instability, adenexal disease (medial canthal entropion, lagophthalmus, eyelid agenesis), and herpes keratitis are associated with the majority of acquired corneal disease in cats. Proliferative/eosinophilic keratitis, acute bullous keratopathy, and Florida keratopathy are common feline nonulcerative disorders. Nonprogressive ulcerative disease in cats, such as chronic corneal epithelial defects and corneal sequestration are more common than progressive corneal ulcerations.

Spontaneous Chronic Corneal Epithelial Defects in Dogs: A Review

Spontaneous chronic corneal epithelial defects (SCCEDs) in dogs are typically found in middle-aged dogs of all breeds. These epithelial defects may be present for weeks to months, particularly if left untreated or if treated inappropriately. Typical histopathological findings include loss of the corneal epithelial basement membrane and formation of a superficial, acellular, hyalinized zone in the stroma. Together, these histological abnormalities lead to delayed wound healing and poor epithelial adhesion. Epithelial debridement, anterior stromal puncture, grid keratotomy, and superficial keratectomy are the most common treatment options applied to the defects. Procedures that address the stromal changes present generally have a higher success rate than epithelial debridement alone.

Thermal cautery of the cornea for treatment of spontaneous chronic corneal epithelial defects in dogs and horses

Australian Veterinary JournalVolume 83, Issue 3 p. 139-139 Thermal cautery of the cornea for treatment of spontaneous chronic corneal epithelial defects in dogs and horses First published: 10 March 2008 https://doi.org/10.1111/j.1751-0813.2005.tb11617.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume83, Issue3March 2005Pages 139-139 RelatedInformation

Thermal cautery of the cornea for treatment of spontaneous chronic corneal epithelial defects in dogs and horses.

A thermal cautery technique was used to treat spontaneous chronic corneal epithelial defects (SCCEDs) in 9 eyes of 8 dogs and 2 eyes of 2 horses. Animals were sedated, and a topical anesthetic was applied. A handheld thermal cautery unit was then used to make multiple, small (< or = 1 mm in diameter), superficial burns throughout the affected area. The cautery unit was applied just until the slightest degree of contraction of the collagen fibrils was observed. After the stromal bed of the defect was treated, a rim of epithelium that extended approximately 1 mm around the denuded stroma was also subjected to thermal cautery. Following surgery, a contact lens was placed in dogs but not in horses, and the eye was treated with broad-spectrum antimicrobial ophthalmic solutions. Defects in all 11 eyes healed with minimal scarring; mean time to healing in dogs was 2.1 weeks (range, 2 to 3 weeks). The defect healed in 1 week in 1 horse and in 2 weeks in the other. Many therapeutic options are available for the treatment of SCCEDs. Procedures such as epithelial debridement and anterior stromal puncture have been shown to have a high rate of success. In cases for which these less invasive procedures fail, our results suggest that thermal cautery may be a reasonable alternative to previously described treatments for SCCEDs in dogs and horses prior to more invasive procedures such as superficial keratectomy.

Diagnosis and management of chronic corneal epithelial defects (indolent corneal ulcerations)

Chronic corneal epithelial defects (CCEDs; indolent corneal ulcerations) are the most common refractory ulcerations in veterinary medicine and are diagnosed by their classic appearance. CCEDs are superficial ulcerations without stromal involvement and have a nonadherent epithelial border (lip). Fluorescein stain adheres to the exposed stroma and extends below the epithelial border, outlining the epithelial lip. CCEDs occur secondary to adnexal disease, keratoconjunctivitis sicca, exposure keratitis, neurotrophic keratitis, and primary corneal disease. In cats, herpes keratitis is associated with the development of CCEDs. Bacterial infections are not responsible for the refractory nature of CCEDs. Because of the refractory nature of CCEDs, treatment can be frustrating for both owner and veterinarian. Current treatment recommendations consist of identifying and treating the underlying cause and performing procedures that stimulate epithelialization and adhesion of the corneal epithelium. Initial treatment of CCEDs includes ulcer debridement and grid keratotomy. Superficial keratectomy is indicated in refractory cases.