Blockade of CD40-CD154 costimulatory pathway promotes long-term survival of full-thickness porcine corneal grafts in nonhuman primates: clinically applicable xenocorneal transplantation.

The porcine cornea may be a good solution for the shortage of human donor corneas because its size and refractive properties are comparable to those of the human cornea. However, antigenic differences need to be overcome to apply xenocorneal transplantation in actual clinical practice. We aimed to investigate the feasibility of full-thickness porcine corneas as human corneal substitutes using a CD40-CD154 costimulatory pathway blocking strategy in a clinically applicable pig-to-nonhuman primate corneal transplantation model. As a result, the mean survival time of the xenocorneal grafts in recipients who received anti-CD154 antibody-based immunosuppressants (POD318 (n = 4); >933, >243, 318 and >192) was significantly longer than that in controls (POD28 (n = 3); 21, 28 and 29; p = 0.010, log-rank test). Administration of anti-CD154 antibodies markedly reduced inflammatory cellular infiltrations (predominantly CD8 T cells and macrophages) into the xenocorneal grafts and almost completely blocked xenoantigen-triggered increases in Th1-associated cytokines, chemokines and C3a in the aqueous humor. Moreover, systemic expansion of memory T cells was effectively controlled and responses of anti-Gal/donor pig-specific antibodies were considerably diminished by programmed injection of anti-CD154 antibodies. Consequently, porcine corneas might be promising human corneal substitutes when the transplantation is accompanied by potent immunosuppression such as a CD40-CD154 costimulatory pathway blockade.

Outbreak of gram-positive bacterial keratitis associated with epidemic keratoconjunctivitis in neonates and infants.

OBJECTIVES: To report the clinical characteristics of bacterial keratitis associated with epidemic keratoconjunctivitis (EKC) and to evaluate the risk factors for bacterial keratitis development in eyes with EKC. METHODS: After 108 patients diagnosed as EKC were retrospectively reviewed, clinical characteristics and incidence of bacterial keratitis-associated EKC were described. To analyse the effect of steroid use and the methicillin-resistant Staphylococcus aureus (MRSA) colonization in conjunctiva on developing bacterial keratitis, HCU-stayed children (n=43) were divided into two groups: those with and those without bacterial keratitis. Other risk factors such as gestational age, duration of hospitalization, MRSA colonization rate of other sites, and interval between follow-ups were evaluated in neonates who stayed in a neonatal intensive care unit (NICU; n=29). RESULTS: Eight out of nine bacterial keratitis developed in HCU-stayed children. All the eight cases of bacterial keratitis occurred in neonates and infants. MRSA keratitis was found in seven hospitalized infants. The incidence of bacterial keratitis was significantly higher in HCU-stayed children than in outpatients (P=0.03), although it never occurred in HCU-stayed adults. The culture-positive rate of MRSA in conjunctiva (P=0.047) and topical use of steroid (P=0.01) were significantly higher in HCU-stayed children who carried bacterial keratitis. The incidence of bacterial keratitis was significantly related with the longer interval of follow-up in early EKC period in NICU in patients (P=0.009). CONCLUSIONS: Infants and neonates show high tendency of MRSA keratitis accompanied with EKC, especially if they were in HCU, applied topical steroid or followed with long interval.

Susceptibility of porcine keratocytes to immune-mediated damage in xeno-related rejection.

We admixed cultured porcine keratocytes or corneal endothelial cells in the presence of human sera or peripheral blood mononuclear cells (PBMCs) for 4 to 72 hours to investigate their immune-related susceptibilities to xeno-related rejection. We evaluated complement deposition at 48 hours by flow cytometry after staining with the C3 anti-goat cy3 antibody. The inhibition of proliferation of porcine corneal cells by human sera was examined using the 3-[4,5-dimethy/thiazol-2,5-dephenyl tetrazolium bromide (MTT) assay over 24 to 72 hours. The amount of 51chromium (Cr)-release was estimated after a reaction between the porcine cells and human PBMCs for 4 hours. There was greater C3 deposition in keratocytes (60.2%) than in endothelial cells (26.9%; P = .05, Mann-Whitney U test). Both keratocytes and endothelial cells showed significant levels of proliferative inhibition over a period of 72 hours. The number of 51Cr-release cells on interleukin-2 addition was significantly higher among keratocytes (88.0%) than endothelial cells (51.4%) at a 1:100 target:effector ratio (P = .04, Mann-Whitney U test). Our present data suggested that porcine keratocytes might be key target cells in xeno-related rejections when the porcine cornea is transplanted to primates.

Short-term effect of intracameral triamcinolone acetonide on corneal endothelium using the rabbit model.

PURPOSE: To investigate the effect of intracameral injection of triamcinolone acetonide on the corneal endothelium in rabbit eyes. METHODS: Triamcinolone acetonide (40 mg/ml, 0.2 cm3) after filtering and resuspension in balanced salt solution (BSS) was injected intracamerally for 3 min into 10 rabbit eyes and irrigated with 5 cm(3) of BSS. Triamcinolone without resuspension and BSS were injected, respectively, into five rabbit eyes. Endothelial toxicity was evaluated and compared by measurements of endothelial cell counts and central corneal thickness. The endothelial viability was determined using vital staining with alizarin red and trypan blue at 2 h after injection. The scanning electron microscopy (SEM) was performed in one cornea from each group. RESULTS: Endothelial cell counts and central corneal thickness following intracameral injection of triamcinolone acetonide did not significantly change when compared to controls. The mean percentage of viable endothelial cells was 99.50, 99.52, and 99.49% in the resuspended triamcinolone group, triamcinolone without resuspension group, and BSS group, respectively (P=0.46, Kruskall-Wallis test). But SEM showed reduced microvilli of endothelial surface in an eye of the triamcinolone without resuspension group. CONCLUSIONS: The intracameral injection of triamcinolone acetonide did not induce a significant visible change of endothelium in rabbit eyes. However, ultrastructural villi changes observed suggest a possibility of microstructural damages in endothelium with triamcinolone acetonide injection when used without filtering and resuspension.

Release of ciprofloxacin from chondroitin 6-sulfate-graft-poloxamer hydrogel in vitro for ophthalmic drug delivery.

The system was designed to use Poloxamer as a vehicle for ophthalmic drug delivery using in situ gel formation property. To enhance the wound healing and cell adhesion as well as transparency of Poloxamer hydrogel, chondroitin 6-sulfate (C6S) was introduced into Poloxamer. For this purpose, mono amine-terminated Poloxamer (MATP), which was end-capped with ethylene amine group only in one side of terminal hydroxyl groups of Poloxamer, was synthesized. Subsequently, C6S-graft-Poloxamer copolymer (C6S-g-Poloxamer) was prepared by reaction between the amine groups of MATP and carboxyl groups of C6S in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carboimide (EDC). The coupling of MATP with C6S was clarified by 1H-NMR and FT-IR spectroscopy. The gelation temperature of graft copolymers was determined by measuring the temperature at which immobility of the meniscus in each solution was first noted. Release behavior of ciprofloxacin from C6S-g-Poloxamer hydrogel in vitro was investigated as a function of C6S content in the graft copolymer by a spectrophotometric assay at 287 nm using an UV spectrophotometer. Differences in the adhesion and morphology of human lens cell between Poloxamer- and C6S-g-Poloxamer-coated surfaces were also investigated. The gelation temperatures of C6S-g-Poloxamer copolymers were lowered with increasing of the concentration of the copolymer and decreasing of C6S content. The release of ciprofloxacin from the graft copolymer was sustained compared with Poloxamer itself and decreased with increasing the content of C6S in the copolymer due to the in situ gel formation of the copolymer and viscous properties of C6S. Human lens cells (B3) adhered to C6S-g-Poloxamer-coated surface were observed as transformed shapes after 2 days. The bioadhesive and thermally gelling of these graft copolymers will be expected to be an excellent drug carrier for the prolonged delivery to surface of the eye.

In vitro and in vivo study of lens refilling with poloxamer hydrogel.

AIM: To evaluate the compatibility of poloxamer hydrogel as a material for an injectable intraocular lens, in vivo and in vitro. METHODS: The appropriate concentration of poloxamer hydrogel was determined for injection by examining the transparency and gelling temperature of this material, assessing the lens capsule refilling technique, and studying the postoperative findings in a rabbit model. RESULTS: Poloxamer hydrogel showed excellent transparency and 25% was identified as an appropriate concentration for the lens refilling material. The authors developed a technique for injecting the material in vivo and obtained excellent short term results. CONCLUSIONS: Poloxamer hydrogel was identified as an appropriate material for direct lens refilling, and the developed injection technique produced excellent short term results.

Release of ciprofloxacin from poloxamer-graft-hyaluronic acid hydrogels in vitro.

Recently, in situ gel formation has extensively been studied to enhance ocular bioavailability and duration of the drug activity. In this study, we report grafting of poloxamer onto the hyaluronic acid for application of tissue engineering oriented ophthalmic drug delivery system. Graft copolymers were prepared by coupling mono amine-terminated poloxamer (MATP) with hyaluronic acid (HA) backbone using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxylsuccinimide (NHS) as coupling agents. The coupling of MATP with HA was clarified by 1H NMR and FT-IR spectroscopy. The gelation temperature of graft copolymers was dependent on the content of HA and the concentration of poloxamer. From drug release studies in vitro, ciprofloxacin was sustainedly released from the poloxamer-g-hyaluronic acid hydrogel due to the in situ gel formation of the copolymer and viscous properties of HA.

Comparative experiments for in vivo fibroplasia and biological stability of four porous polymers intended for use in the Seoul-type keratoprosthesis.

AIMS: To evaluate in vivo fibroplasia and biological stability of porous polymers intended for use in the Seoul-type keratoprosthesis (S-KPro). METHODS: Four porous polymers (polypropylene, two kinds of polyethylene terephthalate (PE70 and PE50), and polyurethane) were investigated. Discs of polymers were inserted into the corneal stroma of rabbits for a 2 and 5 month period. Corneal oedema and neovascularisation were evaluated. The fibroplasia and collagen deposition were examined under light and transmission electron microscopy. S-KPros, whose skirt was made of four types of polymer, were implanted into the rabbits' eyes. The retention time and complications were evaluated. RESULTS: Neovascularisation and corneal oedema were found in all of the disc inserted eyes, but the corneal oedema subsided within 2 months in most of the eyes. The mean number of fibroblasts increased significantly in polypropylene and PE50 disc inserted eyes compared with polyurethane disc inserted eyes. Plentiful collagen deposition was also found in both polypropylene and PE50 disc inserted eyes. Mean retention time in the polypropylene SK-Pro implanted eyes was longer than that of the other eyes (20.7 weeks). The PE70 skirt induced corneal melting around the prosthesis. CONCLUSION: Polypropylene encourages fibroblast ingrowth and shows good biological stability when used as a skirt material in S-KPro.

Effect of poly(ethylene glycol) graft polymerization of poly(methyl methacrylate) on cell adhesion. In vitro and in vivo study.

PURPOSE: To investigate the effect of surface modification of poly(methyl methacrylate) (PMMA) by poly(ethylene glycol) (PEG) grafting on cell adhesion. SETTING: Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea. METHODS: The PMMA surface was oxidized with ozone, and PEG acrylate was then graft polymerized. To verify the PEG grafting on the surface, the oxygen content was measured by electron spectroscopy for chemical analysis. The contact angle was measured using the Wilhelmy plate method. The adhesion of keratocytes on modified PMMA was investigated in vitro. Cultured rabbit keratocytes (4 x10(5) cells/mL) were layered on each PMMA disk, cultured in a carbon dioxide incubator for 24 hours, harvested by trypsinization, and counted. A commercially available intraocular lens was modified as described and then inserted in the anterior chamber of a white rabbit. The cell adherence pattern on the modified IOL was examined by scanning electron microscopy. RESULTS: The PEG-grafted PMMA revealed a higher oxygen content and lower dynamic receding contact angles than the untreated PMMA. The mean number of adhered cells was 72.5 +/- 22 x 10(4)/mL for untreated PMMA. After PEG grafting of 1 hour and ozone oxidation of 2 hours, the adherent cell counts significantly decreased to 6.5 +/- 1.7 x 10(4)/mL and 7.6 +/- 1.6 x 10(4)/mL, respectively (P =.002). Scanning electron microscopy showed small round cells sparsely scattered on the modified PMMA in contrast to the untreated PMMA. CONCLUSION: Surface modification of PMMA using PEG grafting reduced cell adhesion. This may decrease the incidence of retroprosthetic membrane formation after keratoprosthesis surgery.

Development of a newly designed double-fixed Seoul-type keratoprosthesis.

OBJECTIVE: To develop a newly designed double-fixed keratoprosthesis (Seoul-type keratoprosthesis [S-KPro]) and to assess its mechanical stability and biocompatibility. METHODS: Twenty-five rabbits were divided into 4 groups by fixation technique, amniotic membrane (AM) implantation, and skirt material. The eyes were studied with the use of slitlamp, light, and electron microscopy. Stress testing was performed. In addition, 2 human subjects underwent S-KPro implantation. Best-corrected visual acuity was checked, and ophthalmic examination was performed. RESULTS: The average retention period of the group receiving double-fixated polyurethane-S-KPro with AM was longer (>24 weeks) than that of the others. Fibroblast invasions were found in polyurethane pores but not in polytetrafluoroethylene (Gore-Tex) pores on light microscopy. The minimal pressure that induced aqueous leakage was greater than 250 mm Hg in all of the tested eyes. Two human subjects have maintained a good postoperative condition for 18 and 8 months. CONCLUSIONS: The double-fixation technique of applied S-KPro and AM appears to be helpful in improving the stability of the keratoprosthesis. Polyurethane with relatively large pore size (40 microm) may be used successfully as a material for the keratoprosthesis skirt. CLINICAL RELEVANCE: Our results may be important for improving the clinical outcome of keratoprosthesis.

Changes in corneal epithelial barrier function after excimer laser photorefractive keratectomy.

PURPOSE: To use fluorophotometry to measure corneal epithelial barrier function after excimer laser photorefractive keratectomy (PRK). SETTING: Seoul National University Hospital, Seoul, Korea. METHODS: Twenty-five eyes of 21 patients (13 women, 8 men) had PRK to correct myopia. Corneal epithelial healing time was measured and corneal epithelial permeability to sodium fluorescein evaluated by fluorophotometry 1, 2, and 3 weeks after surgery. RESULTS: Epithelial permeability showed a statistically significant increase 1 week after surgery and returned to its preoperative level 1 week later. Comparative studies according to epithelial healing day and corrected diopter showed results that were not statistically significant (P > .05). CONCLUSION: These results suggest that PRK delays complete reconstruction of corneal epithelial barrier function. In humans, the corneal epithelium regained its normal barrier function 2 weeks after PRK. Thus, at least during these weeks, care should be taken to minimize further epithelial trauma.

Two-year follow-up of eyes without topical corticosteroid treatment after photorefractive keratectomy (PRK).

This study was performed to evaluate the result of photorefractive keratectomy (PRK) without topical corticosteroid treatment at postoperative two years. PRK was performed by Summit OmniMed excimer laser, using a 5.0 mm ablation zone in 51 eyes of 29 patients who were then followed up for more than 2 years. During this period, patients who showed myopic regression of less than 1.5 diopters(D) or corneal haze less than grade 2, were regarded as the favorable result group and those who showed myopic regression equal to or greater than 1.5 D or corneal haze greater than grade 1 were regarded as the unfavorable result group. Thirty-four of 51 eyes showed favorable results without any corticosteroid treatment, and 17 eyes showed unfavorable results. In this latter group preoperative mean refractive error (-7.94 +/- 1.58 D) was significantly higher than in the favorable result group (-5.14 +/- 1.30 D) (p < 0.01, t-test); there was, though no statistical difference in age, gender, or corneal thickness. The results were unfavorable in only two of 32 eyes suffering from moderate myopia (< or = -6.0 D), but in 15 of 19 showing high myopia (> -6.0 D). In eyes suffering from moderate myopia, routine topical corticosteroid treatment after PRK does not appear to be necessary.

Effect of the application of human amniotic membrane on rabbit corneal wound healing after excimer laser photorefractive keratectomy.

PURPOSE: We investigated the influence of amniotic membrane application on corneal wound healing after excimer laser photorefractive keratectomy (PRK) in rabbits. METHODS: PRK of -9.9 D with an optical zone of 5.0 mm was performed on each right eye of 34 pigmented rabbits, which had been divided into two groups. In 17 eyes, preserved human amniotic membrane was applied in such a way that it covered the entire cornea for 48 h (amniotic group), and the other eyes formed the control group. The area of epithelial defect, inflammatory cell infiltration, the number of anterior stromal keratocytes, and corneal haze were evaluated. RESULTS: In all animals, the epithelium had healed completely within 3 days, and there was no difference between the two groups. At postoperative 12 and 24 h, the numbers of stromal inflammatory cells in the amniotic group were significantly lower than those in the control group (p = 0.009), and the numbers of anterior stromal keratocytes were significantly higher (p < 0.05). At postoperative weeks 2, 4, 6, 8, and 12, corneal haze scores in the amniotic group were lower than those in the control group (p < 0.05), and at postoperative week 12, the number of anterior stromal keratocytes in the amniotic group was significantly lower than that in the control group (p = 0.002). CONCLUSION: The application of amniotic membrane after PRK reduces keratocyte proliferation and corneal haze during corneal wound healing, possibly by reducing the infiltration of inflammatory cells and loss of keratocytes in the ablation area during the early postoperative period.

Effects of synthetic inhibitor of metalloproteinase and cyclosporin A on corneal haze after excimer laser photorefractive keratectomy in rabbits.

To evaluate the effects of synthetic inhibitor of metalloproteinase (SIMP) and cyclosporin A (CsA) on corneal haze after excimer laser photorefractive keratectomy (PRK) in rabbits, PRK was performed on 60 rabbits. They were randomized to one of four groups: group A which received topical SIMP, group B which received topical CsA, group C which received both SIMP and CsA, and group D which received vehicles. Another 16 rabbits did not undergo PRK and were randomized to one of four groups: group E which received topical SIMP, group F which received topical CsA, group G which received both SIMP and CsA, and group H which received vehicles. SIMP solution (1 mm) was instilled every two hours and 2% cyclosporin was instilled four times a day, this was carried out for as long as 6 weeks after surgery. At one, two, four, and six weeks after surgery, slit lamp examination was performed with haze gradings recorded, and corneal specimens were obtained from groups A, B, C, and D. In groups E-H, all rabbits were killed after six weeks of eyedrops instillation. Light microscopy and immunohistochemistry for collagen types III, IV, and VI were performed on the specimens obtained. Slit lamp examination and light microscopy revealed that SIMP significantly reduced corneal haze after PRK, but CsA did not. Immunohistochemistry revealed that deposition of types III and IV collagen was detected in ablated area in groups A-D, and SIMP reduced the frequency of positive staining for type III collagen. In groups E-F, corneas were normal. These findings suggest that SIMP significantly reduced corneal haze and the synthesis of type III collagen after excimer laser PRK in rabbits.

Effects of gamma-interferon on keratocyte-induced collagen gel contraction and keratocyte proliferation.

PURPOSE: Gamma-interferon has been shown to be an effective immunoregulatory polypeptide that can modulate fibroblastic response. We investigated the effects of gamma-interferon on keratocyte proliferation and keratocyte-induced collagen gel contraction. METHODS: Gamma-interferon in concentrations of 0.01, 1, 100, and 1000 U/ml of media was added to keratocytes embedded in polymerized type I collagen and the gel area was measured after 5 days with an image analysis system. The rate of keratocyte proliferation within and outside the collagen gel under the influence of gamma-interferon was also investigated. RESULTS: Keratocyte-induced collagen gel contraction was significantly inhibited at all concentrations above 0.01 U/ml. The keratocyte proliferation was not affected by low and moderate concentrations and was significantly stimulated at concentration of 1000 U/ml. CONCLUSION: Keratocyte-induced collagen gel contraction is inhibited by gamma-interferon and the mechanism of this effect is not inhibition of keratocyte proliferation by gamma-interferon.

Hydroxyapatite implantation with scleral quadrisection after evisceration.

BACKGROUND AND OBJECTIVES: In contrast to the literature on enucleation, reports of hydroxyapatite (HA) implantation during evisceration are limited; however, those that have been published mention the high HA exposure rate. The authors examined the scleral quadrisection procedure to evaluate its effect on cosmetic appearance and the prevention of HA exposure after evisceration. PATIENTS AND METHODS: The authors analyzed the surgical outcomes of 17 patients who had undergone an HA implantation with scleral quadrisection after evisceration between November 1994 and November 1995. RESULTS: In each case, the authors were able to use HA implants of 18 mm or more. During follow-up (average 10.7 months), there were no cases of conjunctival erosion, HA exposure, implant migration, significant enophthalmos, or superior sulcus deformity. All of the patients, 7 of whom had a ball- and-socket prosthesis, were satisfied with their cosmetic appearance and prosthetic motility. More than 11 weeks after evisceration, all 10 studied patients had complete, round uptakes with orbital bone SPECT (single photon emission computed tomography). CONCLUSION: For good cosmetic appearance and for the prevention of implant exposure, scleral quadrisection is a safe and effective procedure for HA implantation after evisceration.

Dichlorotriazinyl aminofluorescein inhibits human keratocyte proliferation in vitro.

PURPOSE: Dichlorotriazinyl aminofluorescein (DTAF) has been used to stain corneal stromal collagen as part of in vivo experimentation. Toxicity of this drug, if present, might alter the observed wound healing. To determine if this drug has any deleterious effect on keratocytes, we evaluated it in vitro. METHODS: Human keratocytes in 96 well plates were exposed to different concentrations of DTAF (10e-7, 10e-6, 10e-5, 10e-4, 10e-3, 10e-2, and 10e-1 mg/ml of media). Exposure times of 1 and 24 hours at each concentration of DTAF were evaluated. The cell number was measured 1 and 3 days after exposure to the drug using a coulter-counter and a hemocytometer. RESULTS: The proliferation of keratocytes after 24 hours of exposure to the drug was inhibited in a dose dependent manner by DTAF, but 1 hour exposure of keratocytes to the drug did not inhibit keratocyte proliferation. CONCLUSION: These results suggest that DTAF has inhibitory effects on human keratocyte proliferation after 24 hours of exposure, while exposure limited to 1 hour does not induce such a change.

Bacterial keratitis after photoreactive keratectomy in a young, healthy man.

A 34-year-old man who had excimer laser photorefractive keratectomy (PRK) for myopia developed bacterial keratitis from Pseudomonas aeruginosa. He was treated with intensive topical and systemic antimicrobial agents. The eye recovered an uncorrected visual acuity of 20/30. Bacterial keratitis can occur in young, healthy patients after PRK, especially when a bandage soft contact lens is used without appropriate prophylactic measures.

Oxygen free radical damage in the cornea after excimer laser therapy.

AIMS/BACKGROUND: To evaluate the extent of oxygen radical damage in the cornea after excimer laser ablation. METHODS: The 193 nm argon fluoride excimer laser was programmed for an average fluence of 150 mJ/cm2, with a firing rate of 5 Hz and an ablation zone diameter of 6 mm. Phototherapeutic keratectomy was performed to remove 30 microns of epithelium and 50 microns of stroma from the corneas of New Zealand white rabbits. Oxidative tissue damage after laser was determined by measuring oxidised lipids (conjugated dienes and ketodienes) in corneal lipid extracts, and by fast blue B staining to localise the lipid peroxide in the tissue. RESULTS: Conjugated diene levels were 3.73 (SD 0.56) nmol per hemicornea in ablated corneas and 1.99 (0.33) nmol per hemicornea in normal corneas (p = 0.0044). Ketodiene levels were 2.72 (0.38) nmol per hemicornea in treated corneas and 0.91 (0.12) nmol per hemicornea in normal corneas (p < 0.001). Fast blue B staining disclosed that the tissue damage occurred primarily on the surface of the ablated cornea. CONCLUSION: The presence of lipid peroxidation in the superficial corneal stroma in excimer laser treated corneas was demonstrated. This lipid peroxidation could be from oxygen free radicals generated by the infiltrating polymorphonuclear cells at the site of tissue damage.

Short-term effects of flurbiprofen and diclofenac on refractive outcome and corneal haze after photorefractive keratectomy.

PURPOSE: To evaluate the short-term effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs) on refractive outcome and corneal haze after excimer laser photorefractive keratectomy (PRK) according to the degree of myopia and to compare the results with those of topical steroids. SETTING: Seoul National University Hospital, Seoul, Korea. METHODS: Patients were divided into two groups: low to moderate myopia (-6.00 diopters [D] or less) and high myopia (greater than 6.00 D). Then, each patient was randomly assigned to one of three drug subgroups for initial management (4 months post-PRK): corticosteroids (fluorometholone 0.1%); flurbiprofen sodium 0.03% (Ocufen); diclofenac sodium 0.1% (Decrol). Follow-up was 6 months. RESULTS: In eyes with low to moderate myopia, the steroid and diclofenac subgroups had significantly different refractions 2 and 4 months postoperatively but no difference at 6 months; subjective haze grading was consistently lower in the steroid subgroup than in the NSAID subgroups (flurbiprofen, diclofenac) after 2 months. In eyes with high myopia, the steroid subgroup had significantly less myopic regression after 3 weeks and lower subjective haze after 2 months than the NSAID subgroups. The steroid subgroup had severe myopic regression or corneal haze less frequently than the NSAID subgroups. CONCLUSION: Topical NSAIDs were less effective than topical steroids in reducing myopic regression and haze after PRK, especially in highly myopic eyes.