Recurrent Corneal Epithelial Defects Research Articles

MEOHANisMs oF HEALiNG oF OoRNEAL DEFEOTs wiTH THE USE OF SiLiOA DESiCOATiON AMNiOTiO MEMBRANE

The purpose of this work is to study the mechanism of healing of corneal epithelium defect by using silica desiccation amniotic membrane at the cytomorphological level. 7 patients of Samara Regional Clinical Ophtalmologic Hospital named after T.I. Eroshevsky formed the main group of the perforemd study. They were diagnosed with recurrent trophic ulcers of the epithelium and corneal stroma. Their corneal defects were covered with the silica desiccation amniotic membrane. A control group included 5 patients with the same diagnosis. They were observed and treated without amniotic membrane application. Control over the regeneration of corneal defects was carried out by biomicroscopy with fluorescein staining, as well as by cytological examination of impression smears from the surface of the cornea on the 1st, 7th and 15th day after the treatment onset. Patient were being followed up for 6 months. Results. Cytomorphological examination on the 1st day after covering the cornea with the amniotic membrane showed the presence of separate long cells of irregular shape. Both layers of smaller epithelial cells and multiple neutrophils were revealed in the control group. By the 7th day cytograms of the patients in the main group had shown mature cells, impression smears in patients of the control group demonstrated epithelial cells of round shape with darkened cytoplasm and a large number of inclusions. On the 15th day cytograms of patients of both groups almost did not differ. During the following 6 months’ observation recurrent corneal epithelial defects with the inflammatory process were noted in patients of the control group. The main group didn’t show such conditions. Conclusions. Silica desiccation amniotic membrane contributes to the increase in the number of epithelial cells, movement and their firm fixation on the corneal surface as well as reduction of the inflammatory process.

PROSE Therapy Used to Minimize Corneal Trauma in Patients With Corneal Epithelial Defects

To review the effectiveness of continuous or extended daily wear of Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) for treating recurrent or persistent corneal epithelial defects from a variety of causes that were refractory to conventional therapy in 9 patients. Retrospective case series. The medical records of 9 patients with a history of recurrent or persistent corneal epithelial defects resistant to conventional medical treatment who received treatment at the Cullen Eye Institute between January 2011 and July 2012 were reviewed. Demographic information, etiology, prior treatment, and outcome of PROSE treatment were analyzed. Recurrence after cessation of PROSE and complications were also identified. The etiologies of recurrent or persistent corneal epithelial defects in this series included neurotrophic keratopathy, lattice and Avellino dystrophy, Stevens-Johnson syndrome, and chemical/thermal injury. All patients were initially treated with bandage contact lens; however, continuous silicone hydrogel lens wear was not effective in preventing recurrence or healing corneal epithelial defects in all patients. Epithelial defects healed without recurrence in all 9 patients treated with PROSE. Eight patients developed recurrent epithelial defects when PROSE was discontinued, but rehealed after resuming PROSE. Visual acuity improved in 8 patients (88.9%) treated with PROSE. Complex persistent or recurrent corneal epithelial defects that failed to heal with extended silicone hydrogel contact lenses healed with PROSE. PROSE therapy was well tolerated, but corneal epithelial defects recurred in all but 1 case following cessation of therapy.

Difficult cases: Nonstrabimus

Relevance: There are many varied and unique diseases of childhood that may initially present to a pediatric ophthalmologist. It is essential for the pediatric ophthalmologist to be able to systematically approach such diseases and formulate a differential diagnosis to enable one to better understand and manage such diseases. In this workshop we will look at varied disease states including macular hypoplasia an often under diagnosed cause of congenital nystagmus and th appropriate workup in light of recent advances in technology, zinc deficiency as the cause of recurrent corneal epithelial defects and what is the appropriate initial medical work up, the varied presentations, differential diagnosis and management of neonatal conjunctivitis, as well as other cases involving diseases with recent advances in their management.

Ocular manifestations of keratitis– ichthyosis–deafness (KID) syndrome

Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal dysplasia characterized by the association of hyperkeratotic skin lesions, moderate to profound sensorineural hearing loss and vascularizing keratitis. Mutations in the GJB2 gene coding for connexin 26, a component of gap junctions in epithelial cells, have been observed in several KID patients. Variable ocular manifestations of the disease in 3 patients with molecular genetically confirmed KID syndrome are reported. Retrospective case series. Clinical examination and molecular genetic analysis for mutations in the GJB2 gene were performed in 3 patients with KID syndrome ages 5, 13, and 41 years. Visual acuity ranged from normal to severe visual loss. The ocular signs included loss of eyebrows and lashes, thickened and keratinized lids, trichiasis, recurrent corneal epithelial defects, superficial and deep corneal stromal vascularization with scarring, keratoconjunctivitis sicca, and, in one patient, presumed limbal insufficiency. Whereas ocular surface integrity could be maintained with artificial tears in one patient, and an epithelial defect healed under conservative treatment in the second patient, multiple surgical procedures including superficial keratectomies, limbal allograft transplantation with systemic immunosuppression, amniotic membrane transplantation, lateral tarsorrhaphies, and lamellar keratoplasty could not preserve useful vision in the third patient. KID syndrome may affect the ocular adnexae and surface with variable severity independent of the age of the patient. Lid abnormalities, corneal surface instability, limbal stem cell deficiency with resulting corneal complications, and dry eye are the main ocular manifestations.

Hidrotic ectodermal dysplasia with corneal involvement

Background: Persons with ectodermal dysplasias classically have defects in hair, teeth, nails, and sweat glands. Other tissues derived from ectoderm may also be involved. Ocular involvement in ectodermal dysplasias primarily occurs in anhidrotic forms. Methods: We describe a father and son with hidrotic ectodermal dysplasia. Results: Both patients had recurrent corneal epithelial defects from birth, corneal neovascularization, and strabismus. The father had cataracts with crystalline and amorphous inclusions at an early age. Both patients also had alopecia and skin abnormalities. Conclusions: A father and son with a previously unreported hidrotic ectodermal dysplasia and unusual corneal findings are described. (J AAPOS 1999;3:372-5)

Krill protease effects on wound healing after corneal alkali burn.

To study the effect of a novel protease in the development and progression of corneal ulceration secondary to alkali burning. By using a 4N alkali burn model of corneal ulceration in rabbits, the effects and efficacy of topical application of a novel protease (PHM-101) capable of degrading metalloproteinases was studied for 28 days of treatment and 7 days off treatment for its effect on corneal ulceration and recurrent erosion. At day 28, both the protease- and placebo-treated groups had different numbers of eyes showing reepithelialization (nine (45%) of 20 and six (33%) of 18, respectively]. By day 35 the protease-treated group had significantly fewer recurrent epithelial defects [two (13%) of 15 vs. eight (61%) of 13; p = 0.02]. Similarly, at day 35 the protease-treated group showed significantly less corneal ulceration [two (13%) of 15 vs. six (46%) of 13; p = 0.02], and those ulcers were of a lesser severity (three units vs. 17.76 units). No difference was found in the degree of stromal edema or neovascularization, nor was there any difference in histopathologic characteristics of inflammatory cell infiltration and corneal scarring. We conclude that this novel protease is efficient in reducing recurrent corneal epithelial defects and stromal ulceration after alkali burning.

Conjunctival epithelial cells can resurface denuded cornea, but do not transdifferentiate to express cornea-specific keratin 12 following removal of limbal epithelium in mouse

Limbal stem cell deficiency contributes to recurrent corneal epithelial defects. We examined whether the conjunctival epithelium can transdifferentiate to corneal epithelium following surgically induced limbal stem cell deficiency. Mice were anesthetized by intraperitoneal injection of sodium pentobarbital. Partial or total epithelial removal was produced with a no. 69 Beaver blade under a dissecting microscope. The wounds were allowed to heal for 0–28 days, and the mice were examined every other day to evaluate re-epithelialization. Corneas were then subjected to histological, immunohistochemical studies and Western blot analysis with epitope-specific anti-keratin 12 antibodies. Partial epithelial defects re-epithelialized within 2 days and were normal in appearance and expressed cornea-specific keratin 12. In eyes with limbal deficiency, re-epithelialization progressed more slowly and was characterized by opacification; epithelial closure usually occurred by the 7th day. This epithelium differed from normal corneal epithelium in basic morphology, cell shape, and the presence of goblet cells at 2 weeks after injury. The epithelium at the center of injured corneas with total defect at 4 weeks had cornealike morphology and was devoid of goblet cells. These epithelial cells derived from conjunctiva did not express the cornea-specific keratin 12, as determined by immunohistochemistry, Western blot analysis and in situ hybridization. As evidenced by differences in morphology and the expression of cornea-specific keratin 12, conjunctival transdifferentiation does not occur in conjunctical overgrowth after the removal of limbal epithelium.

Expression of K12 keratin in alkali-burned rabbit corneas.

The healing of alkali-injured corneas is characterized by the persistence of polymorphonuclear leukocytes (PMN) in tissues and recurrent corneal epithelial defects. It has been suggested that the proteolytic enzymes secreted by PMN may account in part for the recurrent epithelial defects in the alkali-burned corneas. Cytoplasmic keratins, which form intracellular intermediate filaments, participate in the formation of hemidesmosomes and play a key role in the focal adhesion of epithelial cells to the basement membranes. The K3/K12 keratin pair is a major constituent of differentiated and stratified corneal epithelium. We have recently cloned the cDNA encoding the rabbit K12 keratin. In the present study we examined the expression of K12 keratin during the healing of alkali-burned rabbit corneas by slot-blot and in situ hybridization. Our results indicate that in normal cornea K12 keratin is equally expressed in all cell layers of stratified corneal epithelium and suprabasal layers of limbal epithelium, but not in bulbar conjunctival and other epithelia, i.e., lens, iris, and retinal pigment epithelium. The basal cells of the detached regenerating epithelium of the injured cornea express a very low level of K12 keratin. These observations are consistent with the notion that defective expression of K3/K12 keratins may play a role in the abnormal attachment of the regenerating epithelium to the basement membrane.

Topical Autologous Fibronectin in Patients with Recurrent Corneal Epithelial Defects

We designed a clinical trial to evaluate the effect of topical fibronectin (an adhesive protein) for prevention of recurrent corneal epithelial defects. Fifteen eyes (11 patients) with 2 documented epithelial defects within 12 weeks were included. Purity and biological activity of the prepared solutions of autologous plasma fibronectin were confirmed by sodium dodecyl-sulfate polyacrylamide gel electrophoresis and gelatin binding affinity, respectively. According to randomization, fibronectin or saline was given 5 times per day for 11 weeks to 1 eye of 11 patients. Eyes of 4 patients with bilateral disease were paired, 1 eye receiving fibronectin and the other saline. We examined the patients weekly. The following recurrence parameters were retained for analysis: number of weeks with an epithelial defect, area under recurrence curves, and number of weeks with discomfort. The randomized and paired data analyses suggest that topical autologous plasma fibronectin does not prevent recurrent corneal epithelial defects. We describe a patient who received two treatment courses bilaterally, each eye crossing over to the alternate medication after a first treatment course. The response to treatment of each eye appeared unassociated to the medication.

Topical Fibronectin and Aprotinin for Keratectomy Wound Healing in Rabbits

We evaluated the effect of fibronectin (an adhesive protein) and aprotinin (a protease inhibitor) as single or combined topical therapies for primary healing and prevention of recurrent corneal epithelial defects in the rabbit keratectomy wound model. The biological activity of the prepared solutions of rabbit plasma fibronectin (0.6 g/L) was suggested by in vitro assays of rabbit corneal epithelial cell adhesion and gelatin-binding affinity. In the first experiment, we compared fibronectin, albumin (a control nonadhesive protein), and saline. In the second and third experiments, fibronectin supplemented with aprotinin, aprotinin alone, and saline were compared; aprotinin was used at concentrations of 40 and 1000 kallikrein inactivating units (KIU) per mililiter. Our results suggest that topical fibronectin, 0.6 g/L, as well as aprotinin at 40- and 1000-KIU/mL concentrations, given alone or in combination, neither promote corneal epithelial wound healing nor prevent recurrent corneal epithelial defects in rabbit keratectomy wounds.