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The US Food and Drug Administration recently approved the 193-nm excimer laser for the treatment of superficial corneal pathology and surface irregularities--a procedure called phototherapeutic keratectomy (PTK). Indications for PTK include corneal dystrophies, degenerations, and scars that impair corneal transparency, thus compromising visual acuity. In some cases, PTK may offer a better treatment modality than corneal transplant surgery. This article reviews the basic fundamentals of PTK, including indications for surgery, the surgical procedure, preoperative and postoperative patient evaluation and care, and possible complications.

Background: This study was performed to assess and correlate the changes in central corneal power with the changes in manifest refraction after myopic photorefractive keratectomy (PRK) and to measure ablation zone centration., Methods: Fourteen patients had computerized videokeratography and manifest refraction performed preoperatively, and than 1, 2, 3, 4, 6, and 12 months after photorefractive keratectomy., Results: There was a significant association (r = -0.9; p < 0.0001) between changes in manifest refraction and changes in central corneal power at the 12-month postoperative examination; however, a mean difference of 1.1 D was seen between the two readings. The mean decentration of the ablation zone was 0.47 +/- 0.26 mm (range, 0.08 to 1.05 mm: 0 to 0.49 mm, six patients; 0.50 to 0.99 mm, seven patients; and 1.00 to 1.50 mm, one patient)., Conclusions: Corneal power-as measured by videokeratography-is not an accurate predictor of manifest refraction, although the two parameters did demonstrate good correlation. Centration of ablations was comparable to previous studies.

Purpose: There is mounting evidence that eosinophil granule proteins may cause tissue injury during allergic inflammation of the eye. Therefore, the authors investigated the in vitro effects of human eosinophil major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN) on cultured human corneal epithelial cell viability and morphology., Methods: Confluent primary human corneal epithelial cell cultures were exposed to each of the four human eosinophil cationic granule proteins at concentrations ranging from 0 to 100 micrograms/ml (0, 12.5, 25, 50, and 100 micrograms/ml) for up to 48 hours in serum-free media. Morphologic changes were assessed by light microscopy at 1, 6, 24, and 48 hours; cell viability was measured using the MTT cell viability assay at 24 hours., Results: Cells treated with MBP and ECP induced a dose-dependent gradual increase in morphologic changes; in contrast, EPO and EDN induced minimal changes in cell morphology. At 24 hours, both MBP and ECP induced statistically significant (P < 0.05) decreases in cell viability at a concentration of 100 micrograms/ml; EPO induced a significant (P < 0.05) decrease in cell viability at all concentrations tested, and EDN showed no significant reduction of cell viability at any of the concentrations tested., Conclusions: The current study suggests that the human eosinophil granule proteins MBP and ECP affect human corneal epithelial cell viability and morphology in vitro, whereas the protein EPO affects cell viability only. EDN had no significant effect on cell viability or morphology. Hence, MBP, ECP, and EPO perturb the corneal epithelium differentially and may contribute to keratopathy associated with severe ocular allergy.

Recent reports have demonstrated the expression of intercellular adhesion molecule-1 (ICAM-1; CD54) on the epithelium in various allergic diseases and inflammatory conditions, including the bronchial epithelium of patients with allergic asthma, conjunctival epithelium of allergic patients after allergen-specific challenge, and corneal epithelium of rejected corneal allografts. We investigated the presence of ICAM-1 expression on the corneal epithelium from a patient with vernal keratoconjunctivitis (VKC). Immunohistochemical staining of the diseased cornea demonstrated abundant ICAM-1 expression on the corneal epithelium. Immunoreactive ICAM-1 appeared to localize primarily to the cells of the basal and middle layers of the corneal epithelium. No staining was detected on the ocular surface epithelium. The normal, healthy cornea demonstrated no significant ICAM-1 expression on any of the epithelial layers, similar to that previously reported. To the best of our knowledge, this is the first report of ICAM-1 expression on the corneal epithelium from a patient with VKC.

Objective: To investigate changes in the human corneal endothelium after photorefractive keratectomy for treatment of myopia., Design: Specular microscopy of the central, paracentral, and peripheral zones of the corneas of 14 patients (12 of whom were previous contact lens wearers) was performed preoperatively and at 1, 2, 3, 6, and 12 months after photorefractive keratectomy. The corneal endothelial cell density, coefficient of variation (CV) of the endothelial cell area, and percentage of hexagonal cells were assessed at each examination., Results: The central endothelial cell density was increased by 7% during the first 3 postoperative months (P < .05). In contrast, the peripheral cell density declined steadily by 6.9% during the first year (P < .01). The CV of the cell area was decreased in all 3 zones, whereas the percentage of hexagonal cells was increased in the central and paracentral zones (P < .05)., Conclusions: We observed statistically significant changes in the central and peripheral endothelial cell densities and morphological features that could have resulted from photorefractive keratectomy; however, these changes also may have been explained by the discontinuation of contact lens wear. If such changes are contact lens-related, they could mask the effects of laser-induced damage to the central zone of the endothelium.

Purpose: Human eosinophil major basic protein (MBP) was studied in an established organ culture model for rat corneal epithelial wound healing to elucidate further the role of the protein in vernal keratopathy., Methods: Epithelial migration rates were tested for five MBP concentrations (10, 25, 50, 100, and 200 micrograms/ml MBP)., Results: Significantly less epithelial migration than control (P < 0.05) was observed in all tested groups. Histologic examination revealed abnormally heaped-up leading epithelial edges in all test groups compared to the normal tapered edges in all controls. Immunofluorescence disclosed MBP deposition on deepithelialized cornea., Conclusions: These results suggest that MBP may contribute to vernal corneal ulcerations by inhibiting corneal epithelial migration.

An indirect immunofluorescence assay detected eosinophil granule major basic protein in the inflammatory debris covering deepithelialized cornea in two patients with vernal keratoconjunctivitis. A slight degree of non-specific fluorescence was present in the control autopsy corneas. High concentrations of the eosinophil granule major basic protein inhibit epithelial migration and protein synthesis, whereas low concentrations affect epithelial migration. The results suggest participation of eosinophil granule major basic protein in the ulcerative process.

A cellular late-phase reaction is described in a rat model of topically induced ocular anaphylaxis. Rats were immunized with dinitrophenylated Ascaris suum extract and alum and were tested for active cutaneous anaphylaxis on day 13. Rats with a strong skin test response were selected for ocular challenge with di-DNP-lysine. Macroscopic observation and histologic evaluation were performed at 1, 6, and 24 h. In rats showing a moderate macroscopic ocular response at 1 h, mast cell degranulation was significantly increased at 1 h; no significant increase in eosinophils, neutrophils or lymphocytes was found in the conjunctive of these animals. In rats showing a marked macroscopic ocular response at 1 h, mast cell degranulation was significantly increased at 1 and 6 h; the number of eosinophils was significantly increased at 1 and 6 h, and of neutrophils at 6 h only. At 24 h, neutrophil and eosinophil numbers returned to baseline levels. There was no macroscopic evidence of a late-phase response in either group of animals. Our results suggest that, in keeping with earlier observations in human skin, a strong early response to antigen is required for the development of a late-phase ocular response in the rat.

Attenuation of the rat conjunctival response by repeated topical challenge with dinitrophenyl (DNP) hapten was demonstrated in our study. Adult rats were immunized by intraperitoneal injections of dinitrophenylated Ascaris suum extract (DNP-Asc) and alum. Serum levels of anti-DNP homocytotropic antibody were determined by passive cutaneous anaphylaxis in rats prepared with antibody 48 hours earlier. In other animals, topical challenge was performed by applying N,N'-di-2,4-DNP-L-lysine (di-DNP-lysine) in phosphate-buffered saline (PBS) to one eye; PBS alone was applied to the fellow eye. The degree of conjunctival reaction was assessed clinically, and ocular tissues were processed for histological evaluation. The intensity of the conjunctival reaction and extent of mast cell degranulation were significantly greater after one challenge with di-DNP-lysine than after multiple challenges. In the multiple-challenge group, the contralateral eye remained responsive to a single challenge with di-DNP-lysine. These results may have implications for therapeutic interventions in ocular anaphylaxis.

We tested the effects of pre-treatment with dexamethasone on topically induced ocular anaphylaxis in the rat. Rats were immunized with dinitrophenylated Ascaris suum extract and challenged with di-DNP-lysine. Dexamethasone was administered topically once (24, 6, or 1 h before challenge) or three times (6, 4, and 2 h before challenge). A single pre-treatment given at 24 or 6 h had no significant effect. A single pre-treatment 1 h before challenge reduced the extent of edema assessed histologically but not clinically, and had no significant effect on the eosinophil count in conjunctival tissue examined 6 h after challenge. Eyes pre-treated with dexamethasone 6, 4, and 2 h before challenge showed a significant reduction in conjunctival edema assessed histologically and clinically 1 h after challenge. In addition, 6 h after challenge the number of eosinophils was significantly reduced. We conclude that repeated pre-treatment with dexamethasone can suppress both the immediate phase and the cellular late phase of topically induced ocular anaphylaxis.

Tear fluid cytology is described for the early and late phases of ocular anaphylaxis in actively immunized Sprague-Dawley rats. Tears were collected from both eyes of the rats before challenge and at 1, 2, 4, 6, 8, 10, 12, 24, and 48 h after topical challenge with di-DNP-lysine in one eye and PBS in the fellow eye. Results showed a statistically significant increase in the Aggregate Cell Rating, which represents the aggregate scores in neutrophil, eosinophil, lymphocyte, and atypical epithelial cell levels, in antigen-treated vs control eyes. This report is the first to use a cytologic study of tear film to detect the late phase of ocular anaphylaxis in the rat. Cytology of the tear film could be applied to the study of allergic conjunctivitis in both animals and humans.

A model of topically induced ocular anaphylaxis was developed. Male Sprague-Dawley rats were immunized by intraperitoneal injections of egg albumin (EA) and alum and topically challenged with EA. Application of EA induced clinical (conjunctival edema) and histologic (mast cell degranulation) signs of anaphylaxis, when the antigen was preceded by topical application of dithiothreitol (DTT), a mucolytic agent. Rats challenged by four EA applications did not differ significantly in clinical edema or mast cell degranulation from those challenged by one EA application at the same (0.1 M DTT) pretreatment level, but there was significantly greater histologically assessed edema in the eyes challenged four times.

A hapten (DNP) model of topically induced ocular anaphylaxis has been developed. Rats immunized with DNP-Ascaris were skin-tested with DNP-bovine serum albumin (DNP-BSA) and Evans blue and challenged topically with varying amounts of di-DNP-lysine. The degree of clinical conjunctival edema was assessed, and eye tissues were evaluated histologically. Clinical conjunctival edema and histologic mast cell degranulation increased with higher concentration of di-DNP-lysine. In general, rats with positive skin tests showed more clinical conjunctival edema and more mast cell degranulation than those with negative skin tests. Three other groups of rats with positive skin tests to the DNP-BSA were injected intravenously with 125I-BSA and challenged topically with di-DNP-lysine. Retention of 125I-BSA in ocular adnexa and in globes was higher in di-DNP-lysine- than in PBS-challenged eyes. The hapten model simulates the ocular component of human hay fever in that ocular anaphylaxis is induced in immunized rats by topical challenge with antigen alone.

Cellular events in the rat conjunctiva were studied at 1, 6 and 24 h following the topical application of leukotriene B4. A significant increase was noted in the number of eosinophils (p less than 0.01) and neutrophils (p less than 0.05) at 1 h and only in eosinophils at 6 h after leukotriene B4 application at the 2-micrograms dose. At the 200-ng dose, the eosinophil count was significantly elevated at 1 h only, and the number of neutrophils was not significantly changed at any time point. No significant increase in cell counts was observed at the 20-ng dose. In conclusion, certain doses of topically applied leukotriene B4 significantly increased the number of eosinophils and neutrophils in the rat conjunctiva.

A model of topically induced conjunctival anaphylaxis has been developed. Male Sprague-Dawley rats were immunized by infection with 3000 Nippostrongylus brasiliensis larvae and challenged topically on the eye 4 weeks later. Application of worm antigen alone did not induce clinical (conjunctival edema) or histologic (mast-cell degranulation) signs of anaphylaxis. Topical challenge with antigen 15 min after topical application of dithiothreitol (DTT), a mucolytic agent, elicited conjunctival edema and mast-cell degranulation within the first hour after challenge. At 6 and 24 hr, no clinical change was evident and conjunctival mast cells had again become granulated. At none of the three intervals (1, 6 and 24 hr) was there a significant increase in neutrophils, lymphocytes, eosinophils or macrophages in tissues from DTT-pretreated, antigen-eyes. The present model of ocular anaphylaxis resembles the ocular component of human hay fever in that sensitization prior to challenge is essential, the antigen is presented topically to the ocular tissues, conjunctival edema is the clinical manifestation and mast cell degranulation characterizes the histologic changes.