Robert S. Feder

Expression of wound healing and stress-related proteins in keratoconus corneas.

PURPOSE Keratoconus is characterized by thinning and scarring of the central portion of the cornea. This study was performed on keratoconus corneas to examine the expression of proteins related to wound healing including vimentin, an intermediate filament protein, and tenascin, and extracellular matrix protein. The expression of stress-related cytokines, heat shock proteins and ubiquitin was also investigated. METHODS Corneal buttons were collected from patients with keratoconus, normal subjects and patients with other corneal diseases such as pseudophakic bullous keratopathy. Immunofluorescence staining was performed on frozen sections for vimentin and tenascin, and immunoperoxidase staining was carried out on paraffin sections for cytokines, heat shock proteins and ubiquitin. RESULTS To varying degrees, all proteins examined, except tenascin and heat shock protein 90, were found to be expressed in normal human corneas. The expression of vimentin, tenascin, transforming growth factor-beta, interleukin-1, heat shock protein 27, and ubiquitin was enhanced in keratoconus corneas. A similar enhancement however was also observed in other diseased corneas. CONCLUSIONS Altered expression of several wound healing or stress-related proteins was noted in keratoconus corneas. The alterations appear to be nonspecific injury or wound responses in association with corneal diseases.

Expression of type XII collagen and hemidesmosome-associated proteins in keratoconus corneas.

Purpose. Keratoconus is a disease characterized by thinning of the central and paracentral cornea and scarring in advanced cases. This study was performed to examine the expression of type XII collagen, proteins associated with hemidesmosomes, and ß1 integrin in keratoconus corneas. Methods. Corneal buttons were collected from normal subjects and patients with keratoconus and other corneal diseases. Immunofluorescence staining was performed on frozen sections for type XII collagen, bullous pemphigoid antigen (BP180), and integrin subunits a6, ß4, and ß1. Results. To varying degrees, all proteins examined were expressed in normal human corneas. The staining intensity of type XII collagen was diminished in keratoconus corneas in the epithelial basement membrane zone and the stromal matrix. No significant variation was found in either the staining patterns or intensities for BP180, or integrins a6, ß4, and ß1. Conclusions. The level of type XII collagen was reduced in the epithelial basement membrane zone and stromal matrices in keratoconus corneas. These alterations may affect critical interactions of the corneal epithelium with the under-lying basement membrane, and cell-matrix interactions and matrix organization in the stroma.

Conjunctival Resection for the Treatment of the Rheumatoid Corneal Ulceration

Conjunctival resection is an effective therapeutic modality for the treatment of a marginal furrow associated with rheumatoid arthritis. Rapid reepithelialization was observed following this procedure for the treatment of five such stromal ulcers that occurred in three rheumatoid patients. Keratoconjunctivitis sicca was diagnosed in two of these patients. In four of five ulcers, minimal healing resulted from a prior trial of patching. Conjunctival resection was performed as the primary therapeutic procedure in one case in which perforation seemed possible. A literature review uncovered an additional nine such ulcers in six rheumatoid patients treated by conjunctival resection. In each case corneal healing was observed soon after the procedure. No recurrences were reported on 4- to 24-month follow-ups. This procedure has proven to be effective in each of our rheumatoid corneal ulcers and in each of the case reports in the literature. It would appear to work more reliably than subconjunctival heparin, topical anticollagenases, or immunosuppression. Conjunctival resection is a simple minor room procedure performed under topical anesthesia. It carries minimal risk for the patient. The early use of this technique for rheumatoid stromal ulcers is advocated, especially when the area of ulceration is extensive, when the stromal loss is progressive, and when stromal reserve is minimal. Early conjunctival resection can shorten the hospital stay, and in more severe cases could prevent perforation. Based on successful treatment in a combined total of 14 peripheral rheumatoid corneal ulcerations, the authors believe conjunctival resection should have a more prominent place in the treatment of this condition.

Predictive formula for calculating the probability of LASIK enhancement

Purpose: To develop a formula to predict a patients need for laser in situ keratomileusis (LASIK) enhancement. Setting: Northwestern Laser Vision Center, Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA. Methods: In this retrospective study, charts of patients who received LASIK with the Visx Star excimer laser for myopia and myopic astigmatism were reviewed. Laser in situ keratomileusis enhancement was performed in 130 of 720 eyes. Variables such as age, keratometry, spherical power, power and axis of astigmatism, and surgeon factor were compared in patients who required retreatment and those who did not. Multivariate logistic regression analysis was used to determine a formula for the probability of enhancement surgery. Results: Age (P<.0001), preoperative cycloplegic sphere (P<.0001), and surgeon (P<.0001) were the statistically significant factors for predicting retreatment. The predictive formula derived from these factors had a sensitivity of 79%, a specificity of 61%, and positive and negative predictive values of 31% and 93%, respectively. Conclusions: Older age, higher preoperative cycloplegic sphere, and surgeon significantly influenced a patients likelihood for LASIK retreatment. A formula based on these predisposing factors helps to more accurately predict the need for retreatment.

Intrastromal clefts in keratoconus patients with hydrops

PURPOSE To report the clinical appearance and course of intrastromal clefts occurring with acute hydrops in keratoconus. METHODS In eight patients with bilateral keratoconus, nine eyes developed acute corneal hydrops complicated by intrastromal cleft formation. One patient developed this complication in both eyes. The patients, three female and five male, had a mean age of 20 years (range, 11 to 36 years) and were followed after onset of acute hydrops for a median of 8 months (range, 2.5 to 21 months). The patients in this retrospective study were identified and had been treated at one of two institutional cornea referral practices. RESULTS In eight of nine eyes with intrastromal clefts, complete cleft closure occurred between 6 weeks and 6 months. In one eye, cleft closure was nearly complete in a patient followed up for only 4.5 months after onset of hydrops. Corneal stromal neovascularization developed in six of the nine of eyes. At the last follow-up visit, four of the six untreated eyes had a best-corrected visual acuity of 20/200 or worse. The patient with intrastromal clefts in both eyes did not develop stromal neovascularization and achieved a contact lens corrected visual acuity of 20/40 or better in each eye without surgical intervention. CONCLUSIONS Intrastromal cleft formation is a manifestation of corneal hydrops in keratoconus. Single or multiple clefts can occur, and bilateral involvement is possible. Clefts generally close over a period of months, but stromal neovascularization is common and may compromise future graft survival.

Polymicrobial Keratitis: Acanthamoeba and Infectious Crystalline Keratopathy

PURPOSE To report the early presentation, cause, and successful medical management of combined Acanthamoeba keratitis (AK) and infectious crystalline keratopathy (ICK). DESIGN Interventional case series. METHODS Retrospective review of 111 AK patients diagnosed and managed at the University of Illinois Eye and Ear Infirmary between June 1, 2003 and November 30, 2008 for an additional diagnosis of infectious keratitis. RESULTS Of 5 AK patients with microbiologic evidence of an additional bacterial keratitis during their active AK treatment, concomitant ICK developed in 3 patients. All patients were examined within 3 weeks of their AK diagnosis and were found to have characteristic signs and symptoms consistent with ICK. Bacterial culture results at the time of AK diagnosis were negative in 2 patients, but subsequent culture results were positive for Streptococcus oralis. Initial culture results demonstrated light growth of methicillin-sensitive Staphylococcus aureus in the remaining patient, who had received partial antibiotic treatment. Topical corticosteroids were used before diagnosis in 2 patients and were in use in only 1 patient after AK diagnosis. All infections resolved with medical therapy alone. One patient later required penetrating keratoplasty for visual rehabilitation. CONCLUSIONS In patients with AK, ICK can develop early and without either the use of corticosteroids or a preexisting epithelial defect, inconsistent with previously suggested mechanisms and major risk factors for secondary infection. Combined AK and ICK may exhibit increased pathogenicity with the onset of severe, often new, pain and acceleration of localized tissue loss and resultant scarring. Although early recognition and aggressive medical treatment were successful in resolving the combined infections in our cases, Acanthamoeba coinfection, and perhaps endosymbiosis, should be considered in the evaluation and clinical management of AK, especially in those cases progressing atypically. Further research is needed to understand the precise mechanism of the introduction of coinfectious pathogens and their role in the pathogenicity of AK.

Effect of donor and recipient factors on corneal graft rejection

Purpose: To assess the relationship between donor and recipient factors and corneal allograft rejection in eyes that underwent penetrating keratoplasty in the Cornea Donor Study. Methods: Overall, 1090 subjects undergoing corneal transplantation for a moderate risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) were followed for up to 5 years. Associations of baseline recipient and donor factors with the occurrence of a probable or definite rejection event were assessed in univariate and multivariate proportional hazards models. Results: Eyes with pseudophakic or aphakic corneal edema (n = 369) were more likely to experience a rejection event than eyes with Fuchs dystrophy (n = 676) [34% ± 6% vs. 22% ± 4%; hazard ratio = 1.56; 95% confidence interval (CI), 1.21–2.03]. Among eyes with Fuchs dystrophy, a higher probability of a rejection event was observed in phakic posttransplant eyes compared with those that underwent cataract extraction with or without intraocular lens implantation during penetrating keratoplasty (29% vs. 19%; hazard ratio = 0.54; 95% CI, 0.36–0.82). Female recipients had a higher probability of a rejection event than male recipients (29% vs. 21%; hazard ratio = 1.42; 95% CI, 1.08–1.87) after controlling for the effect of preoperative diagnosis and lens status. Donor age and donor recipient ABO compatibility were not associated with rejection. Conclusions: There was a substantially higher graft rejection rate in eyes with pseudophakic or aphakic corneal edema compared to that in eyes with Fuchs dystrophy. Female recipients were more likely to have a rejection event than male recipients. Graft rejection was not associated with donor age.

The Diagnosis of Epithelial Downgrowth After Keratoplasty

During a two-year period we diagnosed and managed four cases of epithelial downgrowth in aphakic patients (two men and two women, 42 to 76 years old) after keratoplasty. Several clinical findings seemed typical of epithelial downgrowth in this setting. When iritis was present, it was unusual in that the aqueous humor contained large clumps of cellular material and the degree of apparent inflammation was out of proportion to the ciliary flush or symptoms. A posterior corneal line was present in two cases. It resembled an endothelial graft rejection line, but there were no associated keratic precipitates. Also, no graft edema occurred peripheral to a retrocorneal line in either case. Glaucoma was abrupt in onset and difficult to treat. Cytopathologic studies of aqueous aspirate may be needed to confirm the diagnosis. The long-term prognosis for useful vision in our patients was poor but early diagnosis and surgical intervention might possibly lead to a more favorable outcome.

Suture reaction masquerading as a conjunctival malignancy

CASE REPORT We report a case of conjunctival inflammation secondary to a retained suture masquerading as a neoplastic lesion. Excisional biopsy was performed in the right eye on a superior bulbar conjunctival lesion that appeared to be a conjunctival malignancy. A past history of ptosis surgery was obtained. Careful repeated examination with anesthesia, applying traction to the forniceal conjunctiva, revealed an occult polypropylene suture. Despite clinical features typical of malignancy, histologic examination revealed only chronic inflammatory cells. COMMENTS Patients with suspicious conjunctival lesions and a history of ptosis surgery should be carefully explored for retained suture fragments. Examination with anesthesia may be needed to find an occult suture.

Textural interface opacity after descemet stripping automated endothelial keratoplasty: a report of 30 cases and possible etiology.

Purpose: Descemet stripping automated endothelial keratoplasty (DSAEK) has its own set of complications including interface abnormalities. This case series presents the largest number of patients who developed textural interface opacity (TIO) at the graft–host interface after DSAEK. Methods: This is a retrospective multicenter case series of 30 patients from 7 institutions with the finding of TIO. Clinical information collected included donor preparation details, recipient information, and surgical technique. Clinical outcomes included best-corrected visual acuity and status of TIO appearance at the last follow-up visit. Slit-lamp photographs were analyzed and compared. Results: The majority of the patients (73%) had a best-corrected visual acuity of 20/40 or better. Four of the donor tissues were prepared with a microkeratome blade with the same lot number. Six patients had a central interface space between host and donor stromal surfaces—presumed interface fluid but potentially viscoelastic. A slight majority (57%) of patients had improvement in the severity of TIO, with 20% noted to have a complete resolution of TIO (mean follow-up of 11.9 months). Two clinical types of TIO were seen: an elongated type and a punctate type. Conclusions: Most patients with TIO after DSAEK obtain good visual outcomes. TIO spontaneously improves or even resolves during follow-up without intervention. The etiology of this condition is unknown, but we propose 2 different mechanisms. The elongated type could be secondary to an irregular cut of the donor with the microkeratome blade. The punctate type may be secondary to retained viscoelastic.