Quantitative histological studies of primate corneas after excimer laser photorefractive keratectomy.

OBJECTIVE: To evaluate histological changes in the primate cornea after excimer laser photorefractive keratectomy (PRK) and to correlate them with clinical observations. METHODS: Sixteen African green monkey (Cercopithecus aethiops sabaeus) corneas were examined by light and transmission electron microscopy 6 weeks to 18 months after 1.5- or 3-diopter PRK. RESULTS: All specimens had a smooth stromal surface surrounded by a smooth, centrally tapered Bowman's layer. Epithelial thickness appeared to peak 12 months after PRK. The trend was for the epithelium to be thickest in the central-treated area; this phenomenon was more obvious in the 3-diopter-treated corneas. The numbers of activated keratocytes beneath the treated zone peaked at 4 months and decreased thereafter, while the numbers in the untreated areas decreased in the first 2 months after surgery, increased by 4 months, and did not change thereafter. Regenerated basal lamina averaged 86% intact over ablated areas; thickness was normal and no duplications were seen. Overall, the density of hemidesmosomes was significantly less in ablated areas compared with unablated areas. CONCLUSIONS: These findings support the relationship between clinical observations of corneal haze after PRK, reestablishment of the epithelial cell layer, and the potential for stromal remodeling by active fibroblastic keratocytes beneath the ablation zone. Overall, quantification of several morphological parameters indicated that the values for the treated zone tended, with time, to approach those of the untreated cornea after PRK.

Ablation rates and surface ultrastructure of 193 nm excimer laser keratectomies.

PURPOSE: To determine whether photorefractive keratectomy can be performed at lower energies than are currently employed in clinical trials. METHODS: Fresh pig corneas were ablated using a clinical excimer laser to study the effects of various energy densities (100-200 mJ/cm2) and beam diameters on ablation rates and on the surface ultrastructure of the ablated cornea. RESULTS: A 20-mJ increase in energy density was associated with a 0.03 micron per pulse increase in the ablation rate. A nearly linear increase in the pseudomembrane thickness occurred with increasing energy densities (r2 = 0.83) or decreasing ablation area diameter (r2 = 0.86). CONCLUSIONS: Our findings suggest that fluences less than those currently used in clinical trials (160-180 mJ) are capable of ablating tissue while producing thinner electron-dense pseudomembranes on the corneal surface. The relationship between pseudomembrane thickness and clinical factors such as reepithelialization and postoperative haze remains to be determined. Operating at lower fluences does have the advantages of allowing larger diameter ablations, reducing possible shockwave damage, and reducing the maintenance requirements for the laser.

Quantitative analysis of wound healing after cylindrical and spherical excimer laser ablations.

PURPOSE: Superficial corneal ablation using the 193 nm excimer laser for the correction of myopia and astigmatism produces histologic changes in the corneal profile that can be quantitatively analyzed. METHODS: Using the excimer laser, spherical and cylindrical corneal ablations were performed on rabbit eyes at depths of 2, 4, 6, and 8 diopters. After 12 weeks, the corneas were examined histologically using a dichlorotriazinyl aminofluorescein stain for collagen, and the results were quantified using a digital video image analysis system. RESULTS: Epithelial thickness and thickness of new collagen were positively correlated with the depth of ablation after spherical ablations. With astigmatic ablations, epithelial thickness and new collagen production were correlated with ablation depth in one axis only. CONCLUSION: These results suggest that during cylindrical corneal ablations with the excimer laser, radially asymmetrical stromal ablations produce quantitatively asymmetrical wound healing.

Multifocal corneal topographic changes with excimer laser photorefractive keratectomy.

Excimer laser photorefractive keratectomy can flatten the central cornea, thereby eliminating myopic refractive errors; in older patients, however, presbyopia limits satisfaction. Computer-assisted topographic analysis of corneas after refractive surgery indicates that a minority of patients achieve a multifocal lens effect, such that they maintain reasonable acuity over a range of defocus. We have purposefully attempted to create a multifocal refractive effect and have analyzed the subsequent topographies quantitatively to determine if multifocality was achieved. In corneas not operated on and plastic hemispheres, a fairly small range of corneal powers is observed; the range of powers is increased after a monofocal ablation. After multifocal ablations, a greater spread of surface powers is observed, often with a bimodal distribution, indicative of an apparent multifocal effect. These observations suggest that in some patients undergoing photorefractive keratectomy for myopia, it may be possible to reduce symptoms of presbyopia, although a decrease in image contrast or monocular diplopia may complicate this approach.

Photorefractive keratectomy for astigmatism. Initial clinical results.

Excimer laser photorefractive keratectomy, developed to perform radially symmetric ablations to correct myopic or hyperopic refractive errors, was used to perform toric ablations designed to correct cylindrical errors. An expanding slit was used to flatten the cornea in the steep meridian. Four contact lens-intolerant patients underwent this procedure for correction of astigmatism (two patients after penetrating keratoplasty, one patient after corneal ulcer, and one patient with naturally occurring high astigmatism). In each patient, surgery reduced the regular component of the astigmatism; residual irregular astigmatism limited spectacle-corrected acuity in one patient. All patients experienced a shift in spherical equivalent toward hyperopia. Toric ablations with the excimer laser appear to represent a promising strategy for the correction of compound myopic astigmatism that does not rely on creation of deep corneal incisions, excisions, or compression sutures.

Central photorefractive keratectomy for myopia. Partially sighted and normally sighted eyes.

Ten partially sighted and 19 normally sighted eyes underwent excimer laser photorefractive keratectomy for the correction of myopia. Nine of the partially sighted and 17 of the normally sighted eyes had 12 months of follow-up. Epithelial healing was complete in all eyes by day 6. None of the eyes had recurrent erosions, infections, or other medical complications. An increase in corneal haze after surgery was followed by a slow trend toward clearing. Average uncorrected visual acuity in the 7 normally sighted eyes with attempted corrections of 5 diopters (D) or less was 20/40 from month 2 on; the eyes with greater than 5 D attempted corrections had an average of 20/80--at month 2, which declined to 20/200--by month 6. Best spectacle-corrected visual acuity was within +/- 1 Snellen line of preoperative values in 14 of the normally sighted eyes, improved 2 or more lines in 2 eyes, and worsened two or more lines in two eyes. Hard contact lens overcorrection restored all of the two-line loss in 1 eye and 1 line of the 3-line loss in the other. Refraction and keratometry indicated corneal flattening without induced astigmatism.

Photorefractive keratectomy to create toric ablations for correction of astigmatism.

Excimer laser photorefractive keratectomy, developed to perform radially symmetric ablations to correct myopic or hyperopic refractive errors, was used to create toric ablations designed to correct cylindrical errors. An expanding slit was created, with no refractive change intended parallel to the slit opening, and central flattening was induced in the meridian in which the slit was expanded. In polymethyl methacrylate blocks, the induced cylinder (as measured with a lensometer) agreed closely (r2 = .99) with intended change, and in plastic corneas, induction of the cylinder could be demonstrated with computer-assisted topographic analysis. Adult pigmented rabbits underwent induction of toric ablations in two-diopter increments; measured keratometric change correlated with desired change (r2 = .87 at 3 weeks; r2 = .89 at 12 weeks). Toric ablations with the excimer laser appear to represent a promising strategy for the correction of cylindrical errors that do not rely on creation of deep corneal incisions, excisions, or compression sutures.

Central photorefractive keratectomy for myopia. The blind eye study.

Prior to undertaking a study in sighted human eyes, we performed photorefractive keratectomy with the 193-nm excimer laser for the correction of myopia in nine legally blind eyes to evaluate safety, efficacy, predictability, and stability. In most cases, reepithelialization was complete by 5 days after surgery; no recurrent erosions were seen. By the end of the 6-month study, all of the corneas had a 0 or 1+ clarity score, on a scale of 0 (clear) to 5+ (opaque). Keratometry and pachometry demonstrated stable flattening of the corneas. One month after surgery, changes in refraction evaluated by retinoscopy showed fair predictability, with no significant increase in refractive or keratometric astigmatism, followed by some regression of effect by the end of the study, possibly caused by anatomical remodeling. The amount of regression appeared to be directly related to the amount of correction intended, suggesting that this effect would not be clinically important in the treatment of mild to moderate myopia.

One-year refractive results of central photorefractive keratectomy for myopia in the nonhuman primate cornea.

Photorefractive keratectomy for the correction of myopia was performed in 32 eyes of 16 green monkeys. The corneas healed satisfactorily, with normal formation of basal lamina and hemidesmosomal attachments visible in 14-week histologic specimens. No recurrent erosions were observed clinically. After a transient period of faint haze, all corneas were clear at 17 weeks and remained clear through the 1-year follow-up. In terms of accuracy, all corneas demonstrated a significant flattening compared with preoperative values, but no significant difference was seen between the groups with different intended corrections (1.5 and 3 diopters). The changes in corneal shape stabilized by 17 weeks, as measured by keratometry. The clinical results suggest that mechanical removal of the epithelium is preferable to laser ablation of the epithelium. Overall, the results demonstrate that excimer laser ablation of the corneal stroma can produce a stable diptric change in the primate cornea with good healing and long-term corneal clarity.