Growth factor expression in corneal wound healing after excimer laser keratectomy.

PURPOSE: To develop a rabbit model of reproducible corneal haze after excimer laser keratectomy and to characterize expression of transforming growth factor beta (TGFbeta) and basic fibroblast growth factor (bFGF) in rabbit corneas during haze formation. METHODS: Seven rabbits underwent a 100 microm deep phototherapeutic keratectomy (PTK) in one eye and a 15-microm shallow PTK in the contralateral eye. Corneal haze was compared at 1-20 weeks after surgery. Subsequently, 16 rabbits underwent 100-microm PTK in one eye and 15-microm PTK in the contralateral eye. Four rabbits were killed at 1, 2, 3, and 4 weeks, respectively, after surgery. Immunohistochemistry was performed on the corneas to localize the expression of TGFbeta and bFGF. Control subjects were rabbits that underwent either epithelial debridement alone or no surgery. RESULTS: A 100-microm PTK resulted in significantly more corneal haze than a 15-microm PTK at every postoperative examination (p < 0.05). Both TGFbeta and bFGF were expressed in the scars at 1-4 weeks after deep and shallow excimer ablations. bFGF was expressed in the keratocytes of both treated and control corneas. Minimal TGFbeta was detected in the keratocytes of the control corneas, whereas prominent TGFbeta expression was noted in the keratocyte-like cells adjacent to the postkeratectomy scars. CONCLUSIONS: The 100-microm PTK ablation resulted in significantly more corneal scarring than the 15-microm PTK ablation. Even though there was no immunohistochemical difference in the pattern of TGFbeta and bFGF expression after deep and shallow ablations, there was an association between the expression of the growth factors and corneal scarring after excimer laser keratectomy.

Method for safer penetrating keratoplasty in patients with low scleral rigidity.

In eyes with low scleral rigidity, penetrating keratoplasty (PKP) is a high-risk procedure because forward movement of the lens-iris diaphragm can result in prolapse of intraocular contents, expulsive choroidal hemorrhage, and damage to the crystalline lens. We developed a method for safer PKP in eyes with low scleral rigidity. In this technique, the host cornea is incompletely excised and remains attached at the 6 and 12 o'clock positions while the cardinal sutures to secure the donor button over the host are placed. Donor endothelium is protected by an intervening layer of viscoelastic material. After the first 3 cardinal sutures are placed, the host button is completely excised and removed and the donor cornea is sutured. This technique prevents the unopposed forward movement of the lens-iris diaphragm and may reduce the risk of expulsive choroidal hemorrhage and spontaneous extrusion or damage to the crystalline lens during PKP in patients with low scleral rigidity.

Effect of astigmatic keratotomy on spherical equivalent: results of the Astigmatism Reduction Clinical Trial.

PURPOSE: To determine the effect of astigmatic keratotomy on spherical equivalent, as measured by the coupling ratio and a new quantity, coupling constant. METHODS: In a prospective multicenter study, subjects underwent arcuate keratotomy at a 7-mm optical zone by means of the Lindstrom nomogram for correction of astigmatism. One hundred fifty-seven eyes of 95 patients who had a follow-up examination 1 month postoperatively were studied. Mean preoperative refractive cylinder +/- SEM was 2.82 +/- 1.17 diopters. Coupling ratio was defined as the ratio of the flattening of the incised meridian to the steepening of the opposite meridian. Coupling constant was defined as the ratio of the change in spherical equivalent to the magnitude of the vector change in astigmatism. Coupling ratio, coupling constant, and change in spherical equivalent were calculated on the basis of change in refraction and keratometry. RESULTS: On the basis of change in refraction, coupling ratio was 0.95 +/- 0.10 (mean +/- SEM) and coupling constant was -0.01 +/- 0.03, consistent with a minor shift in the spherical equivalent of -0.03 +/- 0.07 diopter. On the basis of change in keratometry, coupling ratio was 0.84 +/- 0.05 and coupling constant was -0.04 +/- 0.02, consistent with minor postoperative keratometric steepening of -0.10 +/- 0.04 diopter. Coupling ratio based on change in refraction was not statistically different from the coupling ratio predicted by the Gauss' law for inelastic domes (P = .370). Incision length and number, amount of achieved cylinder correction, age, and sex had no statistically significant effect on coupling ratio, coupling constant, and change in spherical equivalent. CONCLUSIONS: Cornea behaved as an inelastic surface in response to arcuate keratotomy performed with the Astigmatism Reduction Clinical Trial study nomogram. On average, astigmatic keratotomy had a minimal effect on spherical equivalent refraction. There was variability, however, in coupling ratio, coupling constant, and change in spherical equivalent from eye to eye after astigmatic keratotomy. Caution is therefore advised when simultaneous correction of cylinder and spherical equivalent is planned.

Comparative effects of ketorolac 0.5% or diclofenac 0.1% ophthalmic solutions on inflammation after cataract surgery.

OBJECTIVE: Ketorolac tromethamine 0.5% and diclofenac sodium 0.1% ophthalmic solutions are approved for use by the U.S. Food and Drug Administration to avoid excessive postoperative inflammation after cataract surgery and implantation of an intraocular lens. This study compares the efficacy and toxicity of these nonsteroidal anti-inflammatory drugs for the first time. DESIGN: Randomized, double-masked, prospective clinical trial. PARTICIPANTS: A total of 120 patients assigned in equal numbers to 1 of the 2 treatment regimens. INTERVENTION: Treatment with either ketorolac 0.5% or diclofenac 0.1% ophthalmic solutions instilled four times daily for 30 days beginning the first postoperative day after surgery. MAIN OUTCOME MEASURES: Objective (Kowa FC 1000 laser cell and flare meter) and subjective (slit-lamp biomicroscope) measurements of inflammation and toxicity were made and compared at three separate post-operative visits. RESULTS: The anti-inflammatory effects of the two treatment regimens were not statistically different at any of the postoperative visits. Patients tolerated both treatments equally well. CONCLUSIONS: This study shows diclofenac sodium 0.1% and ketorolac tromethamine 0.5% ophthalmic solutions are equally effective and safe for the control of postoperative inflammation after uncomplicated cataract surgery performed by phacoemulsification followed by the implantation of a foldable intraocular lens.

Retinal function abnormalities in membranoproliferative glomerulonephritis type II.

PURPOSE: To characterize retinal electrophysiologic and psychophysical abnormalities associated with membranoproliferative glomerulonephritis type II. METHODS: Three adults with membranoproliferative glomerulonephritis type II were studied. Retinal function was measured psychophysically (automated perimetry, Farnsworth D-15 color vision testing, and dark adaptometry) and electrophysiologically (full-field flash electroretinography and electro-oculography). RESULTS: Two symptomatic individuals had prominent drusenlike deposits and retinal pigment epithelial disturbances, findings characteristic of membranoproliferative glomerulonephritis type II retinopathy. These individuals had mild visual field and color vision abnormalities, prolonged dark adaptation, and delayed electroretinographic dark-adapted dim and bright flash responses of normal amplitude. The electro-oculogram of the most severely affected individual was abnormal. The third individual who was asymptomatic had the mildest fundus abnormalities and exhibited normal psychophysical and electrophysiologic responses. CONCLUSIONS: Membranoproliferative glomerulonephritis type II retinopathy may be associated with symptomatic and measurable psychophysical and electrophysiologic abnormalities of retinal function.

Benign mixed tumor (pleomorphic adenoma) of the lacrimal gland in a 6-year-old boy.

PURPOSE: To report a 6-year-old boy who had benign mixed tumor (pleomorphic adenoma) of the lacrimal gland. METHODS: A 6-year-old boy was referred for evaluation of a lacrimal fossa mass. We performed a lateral orbitotomy and excised the mass. RESULTS: Histopathologic evaluation of the excised orbital mass disclosed a benign mixed tumor (pleomorphic adenoma) of the lacrimal gland. CONCLUSION: Benign mixed tumors (pleomorphic adenomas) of the lacrimal gland are rare in children. However, they must be considered in the differential diagnosis of pediatric orbital masses because of the prognostic importance of removing a pleomorphic adenoma with the capsule intact.

Basic fibroblast growth factor and local injury protect photoreceptors from light damage in the rat.

Injection of basic fibroblast growth factor (bFGF) into the eye, intravitreally or subretinally, delays photoreceptor degeneration in inherited retinal dystrophy in the rat, as does local injury to the retina (Faktorovich et al., 1990). To determine whether this heparin-binding peptide or local injury is effective in any other form of photoreceptor degeneration, we examined their protective roles in light damage. Albino rats of the F344 strain were exposed to 1 or 2 weeks of constant fluorescent light (115-200 footcandles), either with or without 1 microliter of bFGF solution (1150 ng/microliters in PBS) injected intravitreally or subretinally 2 d before the start of light exposure. Uninjected and intravitreally PBS-injected controls showed the loss of a majority of photoreceptor nuclei and the loss of most inner and outer segments after 1 week of light exposure, while intravitreal injection of bFGF resulted in significant photoreceptor rescue. The outer nuclear layer in bFGF-injected eyes was two to three times thicker than in controls, and the inner and outer segments showed a much greater degree of integrity. Following recovery in cyclic light for 10 d after 1 week of constant light exposure, bFGF-injected eyes showed much greater regeneration of photoreceptor inner and outer segments than did the controls. bFGF also increased the incidence of presumptive macrophages, located predominantly in the inner retina, but the evidence suggests they are not directly involved in photoreceptor rescue. Subretinal injection of bFGF resulted in photoreceptor rescue throughout most of the superior hemisphere in which the injection was made, with rescue extending into the inferior hemisphere in many of the eyes. Remarkably, the insertion of a dry needle or injection of PBS into the subretinal space also resulted in widespread photoreceptor rescue, extending through 70% or more of the superior hemisphere, and sometimes into the inferior hemispheres. This implicates the release and widespread diffusion of some endogenous survival-promoting factor from the site of injury in the retina. Our findings indicate that the photoreceptor rescue activity of bFGF is not restricted to inherited retinal dystrophy in the rat, and that light damage is an excellent model for studying the cellular site(s), kinetics, and molecular mechanisms of both the normal function of bFGF and its survival-promoting activity. Moreover, the injury-related rescue suggests that survival-promoting factors are readily available to provide a protective role in case of injury to the retina, presumably comparable to those that mediate the "conditioning lesion" effect in other neuronal systems.

Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor.

Numerous inherited retinal degenerations exist in animals and humans, in which photoreceptors inexplicably degenerate and disappear. In RCS rats with inherited retinal dystrophy, the mutant gene is expressed in the retinal pigment epithelial (RPE) cell, and leads to the loss of photoreceptor cells. Photoreceptors can be rescued from degeneration if they are juxtaposed to wild-type RPE cells in experimental chimaeras or by the transplantation of RPE cells from normal rats. In both cases, the rescue effect extends beyond the immediate boundaries of the normal RPE cells, suggesting trophic action of a diffusible factor(s) from the normal RPE cells. We considered that the fibroblast growth factors, aFGF and bFGF, might have such a trophic role as they are found in the retina and RPE cells; bFGF acts as a neurotrophic agent after axonal injury in several regions of the central nervous system, and bFGF induces retinal regeneration from developing RPE cells. Here we report that subretinal injection of bFGF results in extensive rescue of photoreceptors in RCS rats for at least two months after the injection, and that intravitreal injection of bFGF results in even more widespread rescue, across almost the entire retina. The findings demonstrate for the first time that bFGF can act as a survival-promoting neurotrophic factor in a hereditary neuronal degeneration of the central nervous system.