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.

Corneal preparation of eye bank eyes for experimental surgery.

PURPOSE: To evaluate the efficacy of dextran in balanced salt solution (BSS) as a preparation of eye bank corneas for experimental surgeries. METHODS: We used 12 eye bank eyes that were unsuitable for transplant. The corneas were removed from the globe and affixed to a Hanna artificial anterior chamber. Four concentrations of dextran-BSS (10%, 15%, 20%, and 30% [+/-0.56%]) were used to dehydrate the corneas, and corneal thickness was assessed with an ultrasonic pachymeter (+/-5 microm) at varying time-intervals over 3 hours. RESULTS: The corneas were thinned to an average thickness of 477+/-54 microm, 430+/-54 microm, 406+/-61 microm, and 391+/-52 microm at average times of 75+/-0 minutes, 85+/-23 minutes, 60+/-12 minutes, and 45+/-0 minutes for the 10%, 15%, 20%, and 30% concentrations, respectively. Corneal thickness was stabilized in both a 15% and a 20% solution. The data was fit to exponential curves until a minimum value was reached, after which linear regression analysis was used to determine the slopes of the data. The slopes for the 15% and 20% concentrations were not significantly different from 0 (p = 0.5 and p = 0.4, respectively). The slopes for each set of data from the 10% and 30% concentrations were significantly different from each other (p = 0.010 and p = 0.001, respectively). CONCLUSIONS: A solution of 20% dextran in BSS is effective for dehydrating eye bank corneas to a quasi-normal physiologic thickness and for maintaining the thickness for a sufficient amount of time. Both the posterior and anterior sides of the cornea should be exposed to the solution for 60 minutes.

Combined pars plana vitrectomy and glaucoma drainage implant placement for refractory glaucoma.

PURPOSE: To report visual acuity and intraocular pressure outcomes among patients who have undergone combined pars plana vitrectomy and placement of a glaucoma drainage implant. METHODS: The medical records of all patients who underwent combined pars plana vitrectomy and placement of a glaucoma drainage implant at the Bascom Palmer Eye Institute by one of the authors between January 1, 1990, and February 28, 1998, were reviewed. Forty patients (40 eyes) were identified, including 14 patients with neovascular glaucoma secondary to proliferative diabetic retinopathy or central retinal vein occlusion, 15 patients with other posterior segment disease, seven patients with secondary angle-closure glaucoma, and four patients with aphakia with ruptured anterior hyaloid face. Main outcome measures included visual acuity and intraocular pressure at 1 year postoperatively. RESULTS: At 1 year postoperatively, 31 (77.5%) of 40 patients had stable or improved visual acuity; three eyes (7. 5%) had a final visual acuity of no light perception and three additional eyes (7.5%) were enucleated (because of chronic pain in two eyes and endophthalmitis in one eye). Mean preoperative intraocular pressure was 34 mm Hg and the median number of preoperative antiglaucoma medications was two. At 1 year postoperatively, mean intraocular pressure was 13 mm Hg and the median number of antiglaucoma medications was zero. Twenty-two patients (55.0%) achieved an intraocular pressure greater than 5 mm Hg and less than or equal to 21 mm Hg without antiglaucoma medication, and an additional seven patients (17.5%) achieved this level of intraocular pressure control with medication. Only one patient (2.5%) underwent further glaucoma surgery for uncontrolled intraocular pressure. CONCLUSIONS: Although combined pars plana vitrectomy and placement of a glaucoma drainage implant is often a successful management option in selected patients with refractory glaucoma, visual outcome may be poor because of severe underlying ocular disease and postoperative complications.

Small peripheral anterior continuous curvilinear capsulorhexis.

Cataract surgery is routinely performed using an anterior continuous curvilinear capsulorhexis (CCC). A manual surgical technique is described for performing a small (less than 1.5 mm diameter) anterior CCC. This technique's applications extend from Phaco-Ersatz, a cataract surgical technique designed to restore accommodation to pediatric cataract surgery. An experimental rabbit study was conducted to determine the feasibility of the technique. Up to 9 small peripheral anterior CCCs were made in the same lens capsule without the capsule tearing. The mean diameter of the CCCs was 1.1 mm +/- 0.3 (SD). A 30 gauge needle and Utrata capsulorhexis forceps were used to construct the CCC. This technique shows promise for the successful performance of small CCCs in Phaco-Ersatz procedures and pediatric cataract surgery.

Synthetic meshwork implant for glaucoma filtering surgery: effect of adjunct heparin and sodium hyaluronate in rabbits.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of a novel filtering implant, a synthetic meshwork (MESH), with or without heparin or sodium hyaluronate amendment. MATERIALS AND METHODS: Eighteen eyes of 18 rabbits received MESH surgery. The eyes were divided into three subgroups. Six eyes received the MESH implant with no modification (group 1), 6 eyes received MESH saturated with heparin (group 2), and 6 eyes received MESH with sodium hyaluronate administration into the anterior chamber during surgery (group 3). Intraocular pressure (IOP) and outflow facility were measured during a period of 6 months. RESULTS: The MESH-implanted eyes showed lower IOP and higher outflow facility than control eyes up to postoperative days 119 and 49, respectively (P > .05). Earliest functional failure was seen in group 3 and latest in group 2. CONCLUSION: MESH implant surgery showed a long-term efficacy in reducing IOP. The beneficial effects of added heparin were limited. Sodium hyaluronate administration reduced the efficacy of the implant device.

Corneal wound healing in monkeys after repeated excimer laser photorefractive keratectomy.

Five rhesus monkey eyes underwent repeated argon fluoride (193 nm) excimer laser myopic photorefractive keratectomy 3 months following an initial ablation that had produced mild subepithelial haze. At 3 months all eyes had development of a dense subepithelial opacity and a thickened epithelium (12 cells, 80 microns) with vacuolization of basal cells, fragmented basement membrane, and a layer of subepithelial fibrosis containing activated fibroblasts. By 6 months the opacity was clearing; epithelium was thinner (50 microns); subepithelial fibrosis was more lamellar. By 15 months only mild haze persisted clinically; epithelium was 30 microns thick, with persistent basal vacuolization and focal basement membrane disruption; subepithelial fibrous tissue was more organized. Early repeated excimer laser ablation of the monkey cornea apparently induces vigorous stromal wound healing. Use of shallower ablations, corticosteroids, or a longer delay between ablations may be necessary for repeated laser surgery to be practical clinically.

Healing of excimer laser ablated monkey corneas. An immunohistochemical evaluation.

The healing response of the cornea following excimer laser anterior keratomileusis (a 4-mm-diameter ablation to a depth of 11, 23, or 46 microns) was analyzed immunohistochemically in adult rhesus monkeys. The ablated surface had reepithelialized and the synthesis of type VII collagen (a major component of anchoring fibrils) was evident by 7 days; the reestablishment of a nearly continuous anchoring fibril zone was evident after 12 weeks. Stromal fibroblasts, activated in response to wounding, expressed a fetal antigen for approximately 6 weeks. Although fibronectin and type VII collagen were present only transiently in the regenerating subepithelial stromal matrix in the subepithelial regions, some other alterations, including the presence of type III collagen, increased levels of keratan sulfates, and discontinuities in the anchoring fibril zone were evident even 18 months after wounding. The depths of the regenerated stroma, which were estimated from the depths of remnant staining for type VII collagen in the stromal matrix, generally, but not always, corresponded to the depths of the calculated ablation.

Corneal wound healing in monkeys 18 months after excimer laser photorefractive keratectomy.

Excimer laser keratomileusis (photorefractive keratectomy, direct corneal ablation) for myopic corrections of 2.00 diopters (n = 1), 4.00 D (n = 4), and 8.00 D (n = 3) was performed on eight corneas of four Rhesus monkeys. All animals were followed for 18 months. The ablations healed normally and no epithelial erosions occurred. Serial slit-lamp microscope examinations revealed that a variable amount of corneal haze developed in all animals; this haze progressively faded during the follow-up period. Histopathology revealed an epithelium of normal thickness, basement membrane abnormalities, increased number and activity of stromal keratocytes, and a variable amount of newly secreted extracellular matrix in the anterior stroma. These findings suggest that excimer laser keratomileusis induces a mild wound healing response in the anterior cornea which displays considerable individual variability and persists up to 18 months.

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.

Accommodation of an endocapsular silicone lens (Phaco-Ersatz) in the nonhuman primate.

In owl monkeys, as a model of endocapsular cataract extraction, the lens material was removed through a small hole in the capsule and was replaced with a silicone polymeric gel. The ability of this endocapsular implant (Phaco-Ersatz) to accommodate was documented when pilocarpine produced an increase in the curvature of the lens surface and a decrease in the anterior chamber depth, just as occurs with the untouched natural lens. Refinements of the surgical technique are required to achieve a controlled degree of filling of the capsular bag and inhibit postoperative epithelial proliferation on the inner capsular surface.

The response of retinal vasculature to angiotensin.

A retinal arterial constriction was produced in anesthetized cats with a continuous transvitreal infusion of angiotensin I or angiotensin II (Ile-5). Constriction of vessels near the infusion cannula tip occurred over a range of angiotensin II concentrations from 10(-9) to 10(-4) molar, and was reversibly blocked by a ten-fold excess of the competitive antagonist saralasin. Constriction did not occur in response to angiotensin I if angiotensin-converting enzyme was blocked with Captopril. Control infusions of saline did not elicit a contraction of the retinal arteries. Severe axonal and inner retinal damage and necrosis occurred when angiotensin II produced a prolonged vasospasm, but not after infusion with control solutions, or when-constriction caused by angiotensin was brief.

Trifluorothymidine and 5-fluorouracil: antiproliferative activity in tissue culture.

The antiproliferative activity of trifluorothymidine (F3TDR) and 5-fluorouracil (5-FU), two cell-cycle-phase-specific antimetabolites, was compared in a tissue culture model of human scleral fibroblasts and rabbit corneal epithelial cells. The mean concentrations required to inhibit human scleral fibroblast proliferation to 50% of the control rate (ID50) after 5 days of exposure were 8.50 micrograms/mL for F3TDR and 0.43 microgram/mL for 5-FU. The corresponding ID50 levels for rabbit corneal epithelial cells were 0.24 microgram/mL and 0.42 microgram/mL. The ID50 of F3TDR was significantly higher than that of 5-FU in human scleral fibroblasts (p less than 0.001) but not in rabbit corneal epithelial cells. F3TDR appears to have no clinical advantage over 5-FU in minimizing corneal epithelial toxicity when given to prevent fibroblast proliferation after glaucoma filtering surgery.

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.