Surgical correction of nearsightedness.
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Biomedical subjects
Publications and source records attributed to K P Thompson.
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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.
We used a Q-switched Nd:YAG laser with non-linear optical crystals to produce the 5th (213 nm) and the 4th (266 nm) harmonic frequencies. Using these two wavelengths, we ablated fresh porcine corneas and type I collagen synthetic epikeratoplasty lenticules. For the 213-nm ablation, radiant exposure was 1.3 J/cm2. The ablation rate was 0.23 micron per pulse for the epikeratoplasty lenticules. We examined all tissues with light microscopy, transmission electron microscopy, and scanning electron microscopy. Histology for the 213-nm ablation showed a clean ablation crater with minimal collagen lamellae disruption and a damage zone less than 1 micron. In comparison, the 266 nm radiation showed more charring at the edges with a damage zone approximately 25 microns deep with disruption of the stromal lamella. Our results show that this solid state UV laser is a potential alternative to the excimer laser for cornea surgery.
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.
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.
Experimental corneal trephination has been achieved with the 193 nm argon fluoride excimer and 2.9 microns hydrogen fluoride and Er:YAG laser systems. Compared with metal blades and other lasers, the 193 nm excimer laser creates the best quality corneal excision, but has a relatively slow etch rate through the stroma, and its use requires toxic gas. The mid-infrared laser systems trephine the cornea in less than 10 seconds, but cause a 10 microns to 15 microns zone of adjacent stromal damage and create wounds that are approximately 2.5 times larger than wounds made by metal scalpels. The wavelength and laser pulse duration influence the cutting characteristics of the laser. Optical delivery systems using an axicon lens, a rotating slit, and a computer controlled scanning optical system have been developed for penetrating keratoplasty. Selection of the optimal laser system for penetrating keratoplasty must await further experimental studies. Refinements of the laser cavity and delivery system are necessary before clinical studies can begin. A carefully controlled randomized clinical trial comparing laser trephination with conventional mechanical trephines will be necessary to determine the safety and efficacy of a laser trephination system.
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Many of the deficiencies with human tissue epikeratoplasty might be improved by the use of a suitable synthetic lenticule. Potential biomaterials for epikeratoplasty include collagen (types I, III, or IV), collagen-hydrogel copolymers, bioactive synthetics, and coated hydrogels. The biomaterial must be engineered to achieve strict specifications of optical clarity, support of epithelial migration and adhesion, permeability to solutes, and stability to corneal proteases. Attaching synthetic lenticules to the cornea without cutting Bowman's layer by adhesives, laser welding, or direct adhesion may also improve the efficacy of synthetic epikeratoplasty.
We used a milliwatt continuous wave CO2 laser mounted on an operating microscope to study the feasibility of welding synthetic collagen epikeratoplasty lenticules to the cornea. In vitro studies and experimentation in rabbits and monkeys showed no welding effects using direct laser radiation with powers ranging from 17 mW to 1 W. Only tissue shrinkage was observed. Experiments using various adjunctive solders produced a temporary welding effect using 30% bovine serum albumin welded with a power of 35-45 mW, 325 microns spot size, moving the beam 5 mm/sec. The lenticules remained in place until the 4th postoperative day when epithelium grew underneath the lenticule, dislodging it. Histopathologic examination demonstrated epithelial migration over the solder displacing the epikeratoplasty lenticule and anterior stromal denaturization and disruption.
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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.
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