Corneal graft survival and intraocular pressure control after penetrating keratoplasty and glaucoma drainage device implantation.

OBJECTIVE: To investigate corneal graft survival rates and intraocular pressure (IOP) control in eyes after penetrating keratoplasty (PK) and glaucoma drainage device (GDD) implantation. DESIGN: Retrospective, comparative, consecutive case series. PARTICIPANTS: All patients who underwent PK and GDD implantation at the Bascom Palmer Eye Institute between January 1, 1993 and October 31, 1998. MAIN OUTCOME MEASURES: Graft clarity and IOP control. RESULTS: Of the 72 eyes in 72 patients identified, 47 (65%) underwent combined PK and GDD implantation, and 25 (35%) underwent GDD placement after PK (2-30 months after PK; median, 13 months). The GDD type was Baerveldt 350 mm(2) in 57 eyes, Ahmed in 9, Krupin in 2, and other in 4 eyes. The GDD was placed in the anterior chamber in 54 eyes (75%) and in the vitreous cavity in 18 eyes (25%). Preoperative IOP was 11 to 53 mmHg with or without antiglaucoma medications in 16 eyes (30%) with the GDD implanted in the anterior chamber and in 4 eyes (22%) with the GDD placed in the vitreous cavity (P = 0.76). At 1 year after GDD implantation, the graft was clear in 26 eyes (48%) with the GDD in the anterior chamber compared with 15 eyes (83%) with the GDD in the vitreous cavity (P = 0.013). Forty-eight eyes (89%) with the GDD in the anterior chamber and 18 eyes (100%) with the GDD in the vitreous cavity had IOP between 5 and 21 mmHg with or without antiglaucoma medications (P = 0.33). The mean reduction in IOP, 1 year after surgery, was 12 mmHg among eyes with the GDD in the anterior chamber, compared with 17 mmHg among eyes with the GDD in the vitreous cavity (P = 0.13) CONCLUSIONS: Corneal graft survival at 1 year is significantly higher among eyes with the GDD implanted in the vitreous cavity compared with those in which the GDD is implanted in the anterior chamber. The IOP was significantly lower at 1 year after surgery compared with before surgery in both groups, and there was no significant difference between the groups in IOP control and amount of IOP reduction. There was no significant difference in corneal graft survival or IOP control between eyes with the GDD implanted concurrently with the PK versus after the PK.

Wound healing after excimer laser keratomileusis (photorefractive keratectomy) in monkeys.

Laser myopic keratomileusis (photorefractive keratectomy) was performed on 29 rhesus monkey corneas with an argon fluoride (193-nm) excimer laser and a computer-controlled, moving slit delivery system. The 4-mm-diameter central ablation zone ranged in depth from 11 microns (-2 diopters effect) to 46 microns (-8 diopters effect). Corneas were studied for the 9 months postoperatively by clinical slit-lamp microscopy, and periodically with light and transmission electron microscopy. By 6 weeks, mild to moderate subepithelial haze was apparent in 93% of the corneas, with considerable variability in density. Progressive clearing occurred so that by 6 to 9 months 12 of 13 surviving corneas (92%) were either completely clear (4 corneas) or trace hazy (8 corneas). The epithelium was thickened at 21 days after ablation and returned to normal thickness by 3 months. At 3 weeks, subepithelial fibroblasts were three times the density of normal keratocytes and returned to nearly normal numbers by 9 months. We concluded that the anterior monkey cornea demonstrated a mild, typical wound healing response after excimer laser keratomileusis.

Effect of excimer laser radiant exposure on uniformity of ablated corneal surface.

The argon fluoride (193 nm) excimer laser is being used to change the anterior corneal curvature for correction of refractive errors. Uniformity of the surface following laser ablation may play an important role in the rate of epithelial healing and amount and type of stromal scarring. To test the effect of radiant exposure (fluence) on surface smoothness, we ablated rabbit corneas with the 193 nm argon fluoride excimer laser at nine radiant exposures from 50 to 850 mJ/cm2. A total energy of 100 J/cm2 was used for each ablation at a frequency of 1 Hz. Scanning electron microscopy demonstrated progressive improvement of surface smoothness with increasing radiant exposures. Transmission electron microscopy demonstrated no consistent increase in thickness to the surface condensate (pseudomembrane) with increasing radiant exposure. Improvement in surface quality associated with increasing radiant exposures may result from a more uniform depth of ablation per pulse in the corneal lamellae that absorb laser wavelengths differently. Radiant exposures at levels where the depth of ablation is the same regardless of increasing energy densities achieve a more uniform surface because inhomogeneities in the beam and variation in energy from pulse to pulse do not affect the ablation rate.

Clinical histologic correlation of human peripapillary anatomy.

The various types of peripapillary crescents which are observed clinically are generally interpreted to represent misalignments of the edges of the neural retina, retinal pigment epithelium (RPE), choroid, and sclera at the disc margin. In order to test the validity of conventional assumptions about the anatomic basis for each type of crescent, the authors compared histologic sections to previously obtained clinical photographs and fluorescein angiograms of 21 eyes enucleated for choroidal melanomas. The authors' results define several configurations of peripapillary tissue, but also show that there can be more than one anatomic basis for some appearances. A scleral lip, which consists of an anterior extension of sclera to separate the choroid from the optic nerve head, is nearly always present, and ophthalmoscopically appears as a white rim that marks the disc margin and accumulates fluorescein after the vascular transit in an angiogram. A chorioscleral crescent occurs when the RPE is retracted from the disc margin, most prominent when associated with a tilted exit canal for the axon bundles through the sclera. In such a crescent, the choroid may be thinned or absent next to the disc, exposing to view some of the underlying sclera. Malposition of the embryonic fold occurs when the boundary between the neural retina and the RPE does not coincide with the embryologically formed fold in the neuroectoderm that occurs at the disc. When this occurs, there is either a double layer RPE (forming a very dark pigment crescent) or a double layer of incompletely formed neural retina adjacent to the disc.(ABSTRACT TRUNCATED AT 250 WORDS)

Subconjunctival 5-fluorouracil mechanisms of ocular penetration.

Aqueous, corneal, and tear film 14C 5-fluorouracil (5-FU) levels were measured in rabbit eyes to better understand the mechanisms of intraocular penetration after subconjunctival injection. Significantly higher aqueous and tear 5-FU levels were achieved one hour after administration when the subconjunctival injection was given transconjunctivally rather than percutaneously through the upper lid [aqueous = 65.7 +/- 9.1 micrograms/ml vs 21.3 +/- 5.1 micrograms/ml (mean +/- SE; p = 0.02, 2-tailed t-test); and tears = 5408.8 +/- 357.3 micrograms/ml vs 228.0 +/- 46.4 micrograms/ml (mean +/- SE; p = 0.004, 2-tailed t-test)]. The aqueous 5-FU levels four hours after transconjunctival injection were significantly greater in anesthetized rabbits without blink reflexes than in those with intact reflexes [32.0 +/- 3.2 micrograms/ml vs 13.4 +/- 0.5 micrograms/ml (mean +/- SE; p = 0.026, 2-tailed t-test)]. The corneal 5-FU levels four hours after transconjunctival injection were greatest nearest the injection site. Direct corneal penetration appears to account for the majority of the aqueous 5-FU concentration after subconjunctival injection; however, there may also be diffusion through the limbus.

Topical fluorouracil. Pharmacokinetics in normal rabbit eyes.

Postoperative subconjunctival fluorouracil injections may be a useful adjunct to standard glaucoma filtering surgery in eyes that are at high risk of failure. Topical administration would be preferable to subconjunctival administration; however, there are no data on the ocular penetration of topically applied fluorouracil. Consequently, we investigated the pharmacokinetics of topically administered fluorouracil labeled with carbon 14 in normal rabbit eyes. One drop (approximately 2.4 mg) of fluorouracil resulted in the following concentrations at 0.5 and six hours, respectively: 17.3 and 0.9 micrograms/g of conjunctiva; 24.3 and 1.3 micrograms/g of cornea; 14.6 and 0.2 micrograms/mL of aqueous; 0.8 and 0.5 microgram/g of lens; 1.1 and 0.3 microgram/g of vitreous; and 0.2 and less than 0.1 microgram/mL of serum. Three drops (approximately 7.2 mg) of fluorouracil resulted in the following concentrations at 0.5 and eight hours, respectively: 589.8 and 1.3 micrograms/g of conjunctiva; 502.9 and 1.8 micrograms/g of cornea; 199.6 and 0.8 micrograms/mL of aqueous; 6.2 and 0.5 micrograms/g of lens; 6.8 and 0.5 micrograms/g of vitreous; and 1.3 and 0.2 microgram/mL of serum. Since a fluorouracil concentration of 0.2 microgram/mL inhibits rabbit conjunctival fibroblast proliferation in cell culture by 50%, these data suggest that topically applied fluorouracil achieves sufficient levels in the ocular compartments and tissues to have potential therapeutic applications.