Transscleral electroretinography.

We studied the electroretinogram in normal patients, patients with opacities of the anterior segment, and patients with vitreous hemorrage, using a high-intensity light stimulus delivered either through the sclera or through the pupil. We found the response obtained with transscleral stimulation a consistent indicator of gross retinal function. Since the stimulus entered the eye through the sclera, it provided a method for studying the retinal responses independent of opaque or translucent media.

Keratocyte survival following a controlled-rate freeze.

One of the major drawbacks of cryorefractive surgery is the delay in the postoperative recovery of corneal clarity. The authors have hypothesized that this delay is due to the death of graft keratocytes caused by the freezing process, and the need for subsequent repopulation by host keratocytes to restore corneal clarity. By using a slow, controlled-rate freeze on a modified Barraquer cryolathe, the authors are able to maintain keratocyte viability in the graft corneal tissue, as assessed by standard histologic methods and by collagenase digestion. Maintenance of keratocyte viability results in the rapid return of corneal clarity following lamellar keratoplasty in the rabbit, with few of the histopathologic changes seen following standard rapid freezing of corneal tissue.

Human alpha and gamma interferon analogs in rabbits with herpetic keratitis.

Complete gene synthesis methods have been used to construct analogs of human interferons (IFNs): these include a consensus of the known human IFN-alpha S, designated IFN-alpha Con1 and a variant of human IFN-gamma, designated IFN-gamma 4A. These interferons, in purified form, were used topically against herpes simplex virus type 1 (HSV-1) induced ocular keratitis in rabbits. Eyes pretreated with IFN-alpha Con1 had decreased signs of infection and a lower incidence of HSV-1 positive trigeminal ganglia (3 of 14 positive) compared to the placebo treated (10 of 14 positive). IFN-alpha Con1 was as effective as natural IFN-alpha subtypes on a units basis, despite the very high specific activity of this analog. IFN-gamma 4A used under similar conditions do not result in beneficial effects with treatments beginning 24 or 48 hr before or 4 hr after virus inoculation. Rabbits with confirmed latent HSV infection were treated topically with IFN-alpha Con1 (10(6) units per eye each day) either before or before and after attempts to intentionally reactivate the infection by bilateral iontophoresis of 6-hydroxydopamine plus topical epinephrine treatment of the corneas. These IFN-alpha Con1 treatment regimens along with intentional reactivation during latency did not: (1) lessen the frequency of inducible ocular shedding episodes; (2) alter the mean time of 3-5 days between attempts to reactive latent infection and the appearance of HSV in tears; or (3) significantly change the incidence of HSV-positive trigeminal ganglia (83-100% HSV positive).

Tobramycin liposomes. Single subconjunctival therapy of pseudomonal keratitis.

The authors compared 24 doses of hourly topical fortified tobramycin (Group A) therapy with a single subconjunctival administration of multivesicular megaliposome-encapsulated tobramycin (Group B) and free subconjunctival tobramycin (Group C) in treating a rabbit model of keratitis caused by Pseudomonas aeruginosa. One cornea each of 50 rabbits was infected with P. aeruginosa for 24 hr. The animals then were divided randomly into five groups of ten each. Groups A, B, and C were treated as described. Group D received liposomes without tobramycin and Group E, hourly balanced salt solution. Significantly fewer Pseudomonas colonies were present in the corneas of all three drug-treated groups (A, B, and C) compared with the two control groups (D and E) at 24 hr (P less than 0.005). Significantly fewer Pseudomonas colonies were present in Groups A and B compared with Group C (P less than 0.02). No significant difference was noted between Groups A and B (P = 0.30). Tobramycin encapsulated in megaliposomes may be useful in treatment of pseudomonal keratitis.

Early changes in refractive error following radial keratotomy.

One hundred twenty-six eyes that had undergone radial keratotomy were analyzed to assess the early changes in refractive error after surgery. Between two weeks and three months, 38% of eyes became more myopic by less than 1 diopter (D), 34% by 1.00 to 1.87 D, and 25% by 2.00 to 3.50 D. Four eyes (3%) had a decrease of 0.25 to 1.25 D. The average increase between two weeks and three months was 1.31 D (SD, 0.9 D). To decrease this change, 15 eyes were semi-pressure patched at night and treated with topical steroids for four weeks following surgery. The average change between two weeks and three months in these eyes was 0.3 D (SD, 1.0 D). This retrospective study suggests that semi-pressure patching after surgery may be useful for eyes that are undercorrected or overcorrected by less than 1 D.

Specular microscopy in pars plana vitrectomy.

A prospective study of endothelial cell loss following pars plana vitrectomy and pars plana vitrectomy with lensectomy was performed in 21 eyes. Fifteen diabetic patients had either vitrectomy alone or vitrectomy with lensectomy. Six nondiabetic eyes were also included in this study. The average cell loss was between 2.3% and 3.9% in all cases. This difference was not statistically significant from the preoperative measurements of endothelial cell counts. These data suggest that pars plana vitrectomy does not result in significant endothelial cell loss, especially when eyes remain phakic or when the anterior capsule is maintained until the end of the case.

Immunoglobulin deposition in the cornea after application of autologous serum.

A 47-year-old man with a history of multiple corneal allografts for recurrent herpes simplex keratitis developed a subtotal nonhealing corneal epithelial defect. The patient was treated with hourly drops of autologous serum. A ringlike infiltrate was subsequently observed, followed by reepithelialization of the graft. The patient later suffered allograft rejection of the cornea and recurrence of the epithelial defect, and a repeated penetrating keratoplasty was performed. Examination of the excised button demonstrated a total epithelial defect, changes compatible with allograft rejection, and, in addition, eosinophilic granular deposits within the superficial corneal stroma that corresponded to the "immune ring" observed clinically. Immunoperoxidase staining was positive for IgG, IgM, IgA, and kappa and lambda light chains. These pathologic changes lend credence to the hypothesis that the precorneal tear film may be a source of immunoglobulin that becomes deposited within the stroma.

Histopathology of corneal neovascularization.

We have developed an experimental model for the quantitative examination of the kinetics of the inflammatory cell response to thermal corneal injury. Using this model, we found a considerable difference in the type of inflammatory cell response to vasculogenic (peripheral) and nonvasculogenic (central) thermal cautery of the cornea. We found that infiltration of the corneal stroma with polymorphonuclear leukocytes preceded the growth of blood vessels in this model. This quantitative model will be useful in future studies of the role of inflammatory cells in different models of corneal neovascularization, and may provide quantitative evidence of how known inhibitors of corneal neovascularization exert their effect.

A comparison of en face and tangential wide-area excimer surface ablation in the rabbit.

We used an argon fluoride excimer laser (193 nm) to perform anterior corneal surface ablation in New Zealand white rabbits (25 eyes) using both en face and tangential methods. We followed up the animals for 90 days using slit-lamp photography and pachymetry at predetermined intervals. We also examined selected tissues with scanning electron microscopy and transmission electron microscopy. Immediate and subsequent examinations revealed significant differences in clarity between the two groups. When viewed through slit-lamp microscopy, the rabbits undergoing the en face method exhibited hazy corneas and irregular surfaces, whereas the corneas that underwent tangential keratectomy demonstrated less haze and fewer surface irregularities. Through histologic study and electron microscopy, we corroborated this finding. At 30 days, there was a statistically significant difference in clarity between en face--treated corneas and those treated tangentially.

Stromal healing following explantation of an ICR (intrastromal corneal ring) from a nonfunctional human eye.

We examined the cornea of the nonfunctional left eye of a 46-year-old man, which was enucleated 8 months following explantation of an ICR (Intrastromal Corneal Ring). Corneal haze was confined to the midstroma, in the region of the tissue from which the ICR had been removed. Stromal tissue in this area was subtly compressed and irregular. Electron microscopy in conjunction with cuprolinic blue staining demonstrated an unremarkable proteoglycan population and several areas of slight collagen disruption at midstromal depth at the site of the previously implanted ICR. We conclude that disruptions of the corneal stroma that remain 8 months following explantation of an ICR are minimal.

Electrosurgical keratoplasty. Clinicopathologic correlation.

A patient with keratoconus who could not tolerate a contact lens underwent electrosurgical keratoplasty. Postoperatively, the central cornea was markedly flattened, but five weeks later the central steepening had recurred. Six months after the procedure, a penetrating keratoplasty was performed. Pathologic examination of the corneal button revealed an intact epithelium and basement membrane. Bowman's membrane was completely destroyed in the treated areas. Stromal scarring extended to involve the anterior two thirds of the corneal stroma. The collagen in this area was contracted and folded. The keratocytes and stromal collagen of the posterior third of the cornea were normal by light microscopy. Descemet's membrane and the endothelium also were normal. Despite the short-lived flattening of corneal topography, this procedure dramatically altered the stromal collagen in the anterior two thirds of the cornea.

The histopathology of corneal neovascularization. Inhibitor effects.

With the use of a previously described model of corneal neovascularization induced by thermal cautery, we examined the effects of inhibitors on both the incidence of corneal neovascularization and the degree of inflammatory cell response. Three known inhibitors of corneal neovascularization, 1% prednisolone acetate, indomethacin, and 0.3% flurbiprofen, were studied and the results were compared with those in saline-treated controls. As expected, corneal neovascularization, preceded by conjunctival and corneal polymorphonuclear leukocyte (PMNL) infiltration, occurred in all control animals. Corneal neovascularization did not occur in any of the inhibitor-treated eyes. Histopathologically, both conjunctival and corneal PMNL counts in the treated eyes were markedly reduced compared with controls. These findings are consistent with the hypothesis that inflammatory cells, particularly PMNLs, are closely associated with the initiation of corneal neovascularization.

Vision research in departments of ophthalmology. An Association of University Professors of Ophthalmology perspective.

A research committee of the Association of University Professors of Ophthalmology disseminated a survey questionnaire to determine the state of research in departments of ophthalmology across the United States. The questionnaire contained 71 questions that were designed to assess attitudes and trends within members' departments and to solicit suggestions from the membership. Of the 145 members and affiliates queried, 140 responded. While the results of the survey indicate significant diversity among departments, departmental chairpersons view research as a major priority in the goals of their departments, and they envision maintenance or expansion of research over the next decade. The survey results have been collated and serve now as the basis for this Association of University Professors position article.

One-year results of the intrastromal corneal ring in nonfunctional human eyes. Intrastromal Corneal Ring Study Group.

OBJECTIVE: The intrastromal corneal ring (ICR), a new keratorefractive device designed to correct myopia, was evaluated for safety and efficacy as part of a phase I Food and Drug Administration clinical trial. PATIENTS AND METHODS: Ten patients, each with one nonfunctional eye, underwent surgical implantation of the ICR, which is a split ring composed of polymethyl methacrylate. The eyes were followed up during a 1-year period and were evaluated for wound healing, implant-related inflammation, intraocular pressure, corneal thickness, endothelial cell count, and refractive effects. RESULTS: Wound healing was uncomplicated in all of the patients. No patient experienced implant-associated inflammation or extrusion. Intraocular pressure, corneal thickness, and endothelial cell counts were unaffected by the ICR. Non-sight-threatening intraoperative events included ring decentration and inadequate attachment of a vacuum-centering guide. The ICR reduced keratometrically determined spherical equivalence by an average of -2.5 +/- 1.1 diopters (mean +/- SD). Spherical equivalence, as determined by retinoscopy, was reduced by an average of -2.4 +/- 1.0 D. Results of corneoscopy and computerized videokeratography further confirmed this reduction of myopia. CONCLUSIONS: The ICR may be a safe and efficacious device that offers predictable results with few side effects, and it may be a feasible alternative to current keratore-fractive procedures.

Alternate and classical pathway components of complement in the normal cornea.

Activation of complement by either the classical or alternate pathway may be involved in corneal inflammation. This study was undertaken to determine whether the normal human cornea contains components for both classical and alternate pathway activation of complement. Direct immunofluorescence of corneas from human donors using fluorescein-labeled antiserums was used to demonstrate C1q, C3, C4, and C5. The C1q component (the recognition unit of the classical pathway and largest complement component) was found in the periphery of the cornea. Normal donor corneas were also eluted in phosphate-buffered saline at 4 degrees C for one to four days. Ouchterlony plates, in which the corneal eluate was reacted against antiserums to complement components, disclosed the presence of C1q, C3, C4, C5, properdin, and properdin factor B. Plasminogen was also found. Radial immunodiffusion was used to obtain estimates of the concentrations of C3, C4, and C5 in the cornea.

Oral acyclovir reduces the incidence of recurrent herpes simplex keratitis in rabbits after penetrating keratoplasty.

To determine if acyclovir sodium prevents postoperative herpes simplex virus type 1 (HSV-1) recurrences, 21 rabbits harboring latent HSV-1 underwent uniocular autograft penetrating keratoplasty. All operated-on eyes were treated with topical and subconjunctival dexamethasone sodium phosphate. Ten of the 21 rabbits also received oral acyclovir (intravenous acyclovir was given at the time of surgery). Postoperatively, 9 (82%) of 11 operated-on eyes in rabbits not treated with acyclovir had positive HSV-1 ocular cultures. In acyclovir-treated rabbits, however, none of the 10 operated-on eyes had positive ocular cultures. In addition, 9 (82%) of 11 of the operated-on eyes had geographic ulcers develop in the non-acyclovir-treated rabbits, compared with 1 (10%) of 10 in the acyclovir-treated rabbits. Finally, stromal keratitis appeared in 5 (56%) of 9 of the operated-on eyes in non-acyclovir-treated rabbits and 1 (12%) of 8 of the operated-on eyes in acyclovir-treated rabbits. The results of this study indicate that acyclovir significantly lowered the incidence of HSV-1 ocular shedding, geographic ulceration, and stromal keratitis in a rabbit autograft penetrating keratoplasty model.

An update of the indications for penetrating keratoplasty. 1979 through 1983.

We performed a retrospective analysis of the clinical and pathologic diagnoses of 497 corneal buttons that had been submitted to the Estelle Doheny Eye Pathology Laboratory, Los Angeles, during the five-year period 1979 through 1983. The leading indications, in order of decreasing frequency, were pseudophakic bullous keratopathy (17.5%), regrafts (15.1%), aphakic bullous keratopathy (10.9%), corneal trauma (9.3%), and Fuchs' endothelial dystrophy (9.1%). The emergence of pseudophakic bullous keratopathy as the most common cause for penetrating keratoplasty correlates well with the dramatic increase in the number of cataract extractions with intraocular lens implantations performed since the mid-1970s. Less frequent indications for penetrating keratoplasty included the following: corneal scars (6%); active ulcerative keratitis (7%); keratoconus (6%); keratitis secondary to virus (5%); non-Fuchs' corneal dystrophies (3%); congenital corneal opacities (3%); interstitial keratitis (2%); and chemical burns (1%).

Ocular involvement in the respiratory vasculitides.

The respiratory vasculitides are idiopathic inflammatory syndromes, characteristically involving the pulmonary vasculature as well as that of several other organ systems. The inflammatory response in these diseases is uniformly granulomatous. There are three distinct, recognized respiratory vasculitides: Wegener's granulomatosis, Churg-Strauss syndrome (allergic granulomatosis and angiitis), and lymphomatoid granulomatosis. Each of these entities may have ophthalmic manifestations, and ocular involvement may, in fact, be the presenting sign. The systemic and ocular manifestations, as well as the differential diagnosis and management of each of these entities are discussed.

Ocular drug bioavailability from topically applied liposomes.

During the past decade liposomes have been investigated extensively for their ability to improve drug utilization by the body, first in the area of chemotherapeutics and most recently in the area of ophthalmology. Liposomes are vesicle-like structures with a concentric series of alternating compartments of aqueous spaces and phospholipid bilayers. To date, liposomes have been found to both promote and reduce ocular drug absorption, indicating that a definite need exists for further studies to evaluate the interplay of drug, liposomes, and the corneal surface in determining the effectiveness of liposomes as vehicles for topically applied ophthalmic drugs. The purpose of this review is to place in perspective the role of liposomes in topical ocular drug delivery. As background material, the factors influencing ocular drug bioavailability and the features of liposomes pertinent to their effectiveness as drug carriers are reviewed.

Peripheral corneal disorders.

The peripheral cornea is anatomically and physiologically distinct from its central counterpart. The major differences relate to the gradual transition of corneal tissues to those of the conjunctiva, episclera, and sclera; furthermore, the vascular structures, lymphatics, and inflammatory cells from these neighboring structures are intimately associated with the limbus and periphery of the cornea. The peripheral cornea is thereby predisposed to three main classes of disorders which do not normally involve the central cornea. First, local conditions affecting the sclera and conjunctiva may secondarily spread to involve the limbus and peripheral cornea. These include several infectious diseases, as well as hypersensitivity conditions, mass lesions, and degenerations. Second, due to the associated blood vessels and lymphatics, the peripheral cornea may be involved in a variety of systemic diseases, including vasculitides, autoimmune disorders, and abnormal metabolic conditions. Finally, there are several conditions, such as the noninflammatory peripheral degenerations, which primarily affect the peripheral cornea without associated ocular or systemic changes. In this review, we present a classification and discussion of the various disorders which may involve the peripheral cornea.