Indications for penetrating keratoplasty and associated procedures, 1989-1995.

PURPOSE: To identify changing trends in indications for penetrating keratoplasty and associated surgical procedures. METHODS: Review of charts from all patients who underwent penetrating keratoplasty at Wills Eye Hospital from January 1, 1989 through December 31, 1995. RESULTS: A total of 2,442 corneal transplants were performed in 2,186 patients. The leading indication for penetrating keratoplasty was pseudophakic corneal edema, accounting for 634 cases (26.0%); 54.7% of them were associated with anterior chamber intraocular lenses, 36.4% with posterior chamber intraocular lenses, and 3.1% with iris-fixated intraocular lenses. Regraft (17.8%), Fuchs' dystrophy (15.7%), and keratoconus (13.2%) followed pseudophakic corneal edema in frequency. Cataract extraction, with or without intraocular lens implantation, was combined with penetrating keratoplasty in 439 cases of 1,264 phakic eyes (34.7%). Intraocular lens exchange was performed in 285 of the 634 cases of pseudophakic corneal edema (44.9%). CONCLUSION: Pseudophakic corneal edema was the leading indication for penetrating keratoplasty, with an increasing number of cases associated with posterior chamber intraocular lenses during the study period (p = 0.001). The number of regrafts steadily increased between 1989 and 1995 (p = 0.001), being the second most common indication for corneal transplantation since 1992.

Use of routine antibiotic sensitivity testing for the management of corneal ulcers.

OBJECTIVE: To prospectively evaluate the clinical importance of antibiotic sensitivities for the management of corneal ulcers. METHODS: Thirty-two consecutive patients referred to the Cornea Service at Wills Eye Hospital, Philadelphia, Pa. between October 1, 1993, and May 31, 1994, with a culture-positive corneal ulcer were studied prospectively. Broad-spectrum empirical antibiotic therapy with intensive topical fortified antibiotics was initiated after smear and culture results were obtained. The therapy was modified based on clinical appearance, stain results, or organism identification. Clinicians were masked to the sensitivity results. RESULTS: Fifteen patients healed after receiving the initial empirical antibiotic therapy (group 1). The antibiotic regimens of 6 patients were modified after the stain and/or culture results were available, although the clinical appearance suggested continued improvement while taking the initial regimen (group 2). Eleven patients had ulcers that either failed to improve or worsened after receiving the initial empirical therapy (group 3). Seven of these patients ultimately improved with a change in therapy; treatment failed in 4 patients. Nine patients (5 for whom antibiotic therapy succeeded and 4 for whom it failed) should have been adequately treated by the initial antibiotic therapy, according to sensitivity results. In the remaining 2 patients, in vitro sensitivity testing did not include the antibiotics used for the initial treatment. In all cases, the organisms were sensitive to the empirically altered regimen of antibiotics. CONCLUSIONS: These preliminary results suggest that routine antibiotic susceptibility tests do not provide clinically useful information for the management of corneal ulcers. The identification of the organisms based on the results of smears and cultures was sufficient for the selection and modification of topical antibiotic therapy.

The roles of tissue inhibitors of metalloproteinases in tissue remodelling and cell growth.

Tissue inhibitors of metalloproteinases (TIMPs) are secreted proteins that block the activities of the extracellular matrix (ECM)-degrading metalloproteinases (MMPs). As key determinants of ECM integrity and turnover, TIMPs are involved in the establishment and maintenance of tissue architecture and may indirectly influence ECM-dependent cells signaling. In addition, TIMPs exert both positive and negative effects on cell growth through mechanisms that are independent of MMP inhibition. The three members of the mammalian TIMP family differ in structure, biochemical properties and expression, suggesting that they have distinct physiological roles. Here, we review recent advances in our understanding of TIMP protein function and gene regulation. We discuss the potential relevance of MMPs and TIMPs in obesity with regard to effects on the processing of tumor necrosis factor-alpha.

Corneal neovascularization after penetrating keratoplasty.

The purpose of this study was to delineate the patient and surgical factors that contribute to the development of corneal neovascularization (CNV) after penetrating keratoplasty (PK). Thirty-six eyes of 36 patients with no antecedent CNV were enrolled in the study. Grafts were sutured to the host with 16 10-0 nylon sutures with the knots buried alternately in either the host or donor corneal stroma. Multiple perioperative factors were recorded for each patient, and at each postoperative visit systematic corneal drawings were used to follow the development of neovascularization. The stroma adjacent to each suture of each graft was given a neovascularization score based on the extent of vessel growth toward the wound interface. Univariate and multivariate analyses were performed, including generalized estimating equations logistic regression where each eye is considered a cluster of observations. Thirty-four patients without preoperative CNV or inflammation were followed prospectively for 6-9 (mean, 7) months after PK. Fourteen eyes (41%) developed some degree of CNV. Indication for keratoplasty, age, gender, phakic status, and size of donor button were not risk factors for CNV development. The most significant risk factor identified for any degree of CNV was placement of the suture knot in the host stroma (p = 0.00007), with the overall relative risk of CNV associated with these knots over 2 (95% confidence interval, 1.1-4.2). Furthermore, the mean recipient size in eyes with postoperative CNV was larger than eyes that did not develop neovascularization (p = 0.015), and active blepharitis was associated with a fivefold increase in the risk of developing CNV to the wound edge (p = 0.008). Embedding suture knots in the host stroma, active blepharitis, and a large recipient bed are significantly associated with postkeratoplasty CNV.

Peripseudophakic membrane. Pathologic features.

A 70-yr-old woman underwent anterior segment reconstruction with repeated penetrating keratoplasty for visual rehabilitation. On removal of the failed keratoplasty button, the posterior chamber intraocular lens was found to be encased in a dense fibrous membrane that almost totally obliterated the anterior and posterior chambers of the eye. Anterior segment reconstruction included excision of the fibrous membrane, removal of the intraocular lens, iridoplasty, gonioplasty, anterior vitrectomy, and repeated penetrating keratoplasty. Recognition of fibrous tissue that extended through each of the four positioning holes of the optic of the lens implant and its transection was essential in avoiding complications during removal of the intraocular lens. Histopathologic and ultrastructural examination of the excised membrane revealed areas of metaplastic lens epithelium and fibrous scar tissue. This study, using immunofluorescence, is the first, to our knowledge, to characterize the specific collagenous components of a peripseudophakic membrane.

Microfilaments, microtubules, and intermediate filaments in cultured corneal fibroblasts.

Corneal stromal fibroblasts play an important role in wound healing. Proteins from all three cytoskeletal classes (microfilament, microtubule, and intermediate filament) are involved in the control of various cellular events, such as motility, cell adhesion, shape changes, intracellular transport, and mitosis. By epifluorescent light microscopy, we studied the intracellular distributions of actin (microfilament), tubulin (microtubule), and vimentin (intermediate filament), as well as vinculin (a junctional protein connecting microfilaments to the cell membrane), in cultured corneal fibroblasts. Mutual positional relationships between actin and the other cytoskeletal proteins were investigated by double-labeling. Particular attention was paid to the leading edge of spreading or migrating fibroblasts and to their cell-to-cell contacts.

Differential action of somatostatin on peptide-induced release of acetylcholine.

In this study we examine the mechanism by which somatostatin (SRIF-14) inhibits cholecystokinin octapeptide- (CCK-8) but not substance P-mediated release of [3H]acetylcholine (ACh) from the guinea pig ileum. 2',5'-Dideoxyadenosine, an inhibitor of adenylate cyclase, antagonized the action of CCK-8 and forskolin but had no effect on substance-P-evoked release of [3H]ACh. Addition of theophylline enhanced the release of [3H]ACh stimulated by CCK-8 but not by substance P. These observations suggest that CCK-8, but not substance P, can stimulate cholinergic transmission via an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent pathway. Somatostatin inhibited release of [3H]ACh evoked by CCK-8 and forskolin in a dose-related manner. CCK-8- and forskolin- but not substance P-evoked release of [3H]ACh were maximally inhibited in the presence of 10(-6) M somatostatin (49 +/- 5 and 48 +/- 7% of control, respectively). Pretreatment with pertussis toxin (inactivates inhibitory guanine nucleotide binding proteins) reversed the inhibitory effect of somatostatin on the release of [3H]ACh evoked by CCK-8. These observations suggest that CCK-8 but not substance P can stimulate [3H]ACh by a cAMP-dependent pathway. Somatostatin appears to inhibit the cAMP-dependent component of CCK-8-mediated cholinergic transmission via activation of a pertussis toxin-sensitive G protein.

Implantation of posterior chamber intraocular lenses in the absence of lens capsule during penetrating keratoplasty.

We retrospectively studied the clinical records and the corneal endothelial cell counts of 133 consecutive eyes that received sutured posterior chamber intraocular lenses during penetrating keratoplasty in the absence of lens capsular support. Postoperative follow-up time ranged from three to 24 months, with 82 patients having at least one year of follow-up. At one year, 45.1% of these patients had 20/40 or better visual acuity, 30.5% had a visual acuity between 20/50 and 20/100, and 24.4% had a visual acuity of 20/200 or worse. At two years, 63.6% had a visual acuity of 20/40 or better, 18.2% had a visual acuity between 20/50 and 20/100, and 18.2% had a visual acuity of 20/200 or worse. Ninety-seven percent of the grafts remained clear at their latest follow-up examination. Cystoid macular edema (36.4%) and age-related macular degeneration (14.0%) accounted for poor visual acuity in most cases. Less common problems included graft rejection, retinal detachment, glaucoma, and endophthalmitis. At one year, the endothelial cell loss in the grafts averaged 19% with sutured posterior chamber intraocular lenses.