Randy J. Epstein

Topical Mitomycin-C for subepithelial fibrosis after refractive corneal surgery

OBJECTIVE To determine the effectiveness of mitomycin-C (MMC), 0.02%, in preventing recurrence of corneal subepithelial fibrosis after debridement and/or keratectomy in patients who have undergone refractive corneal surgery. DESIGN Noncomparative case series. PARTICIPANTS Eight eyes of five patients with corneal subepithelial fibrosis who had previously undergone radial keratotomy (n = 4) or photorefractive keratectomy (n = 4). INTERVENTION All eyes underwent epithelial debridement followed by a single intraoperative application of MMC (0.02%) for 2 minutes followed by saline irrigation. The eyes were then patched, or a bandage contact lens placed until epithelial healing was complete. MAIN OUTCOME MEASURES Corneal clarity and best-corrected visual acuity (BCVA). RESULTS In all cases, the cornea remained clear with no recurrence throughout the follow-up period (6-25 mos., mean, 13.8 mos). No adverse reactions were reported. BCVA improved in all cases. CONCLUSIONS Subepithelial fibrosis can be a visually disabling condition after refractive corneal surgery. Topical application of MMC (0.02%) may be a successful method of preventing recurrence of subepithelial fibrosis after debridement.

Corneal neovascularization. Pathogenesis and inhibition.

Corneal neovascularization (CNV) can cause significant visual loss because of the scarring and lipid deposition that frequently accompany it. In addition, penetrating keratoplasty in a vascularized recipient carries a significant risk of failure from allograft rejection. Frequently CNV is induced by nonspecific inflammatory stimuli, mediated primarily by polymorphonuclear neutrophils. Neovascularization can also be associated with specific corneal immune reactions, such as herpes simplex keratitis. Immunologically mediated CNV may be more amenable to treatment than CNV that results from nonspecific inflammation. Photodynamic therapy (PDT) following the intravenous injection of hematoporphyrin derivative or purified dihematoporphyrin ether (DHE) has been shown to suppress tumor growth and blood vessel growth in the eye. We have developed a murine model of CNV induced by the intrastromal injection of stimulated lymphocytes or interleukin-2 (IL-2). We have noted corneal DHE retention following its intravenous injection in mice with IL-2 induced CNV. Preliminary studies indicate that PDT can induce regression of CNV in these mice. Other recent studies that have enhanced our understanding of the pathogenesis and treatment of CNV are reviewed, and directions for future research are discussed.

Acanthamoeba Keratitis: A Growing Problem in Soft and Hard Contact Lens Wearers

Eleven contact lens-wearing patients presented with Acanthamoeba keratitis. Eight cases were culture- and/or stain-positive for Acanthamoeba and three were presumed to have Acanthamoeba keratitis based on history and clinical findings. Six wore daily wear soft contact lenses, two wore extended-wear soft contact lenses, one wore a polymethylmethacrylate hard contact lens, one wore a gas-permeable hard contact lens, and one wore a Saturn lens (combined hard and soft lens). Four patients used distilled water and salt tablet saline, three used tap water and salt tablet saline, two used tap water rinse, two used well water rinse or storage, and one used intravenous (IV) saline. It is apparent that all contact lens wearers are at some risk for Acanthamoeba keratitis developing if proper contact lens care is not maintained. Of great concern is the inability of most current chemical sterilization methods to kill the organism if the lens becomes contaminated. Heat disinfection will kill Acanthamoeba trophozoites and cysts but the lens must not be placed into contaminated solutions afterward. Prevention is very important because medical and surgical treatment failures are frequent. Eye care practitioners who fit contact lenses are advised to use heat disinfection for low-water content stock soft contact lenses, and to use hydrogen peroxide without a catalyst for a minimum of 6 hours for all other stock lens fitting sets, to specifically inquire about contact lens care habits used by their patients, and to discourage the use of homemade saline solutions.

Early Onset Ectasia Following Laser in situ Keratomileusus: Case Report and Literature Review

PURPOSE Laser in situ keratomileusis (LASIK) has been associated with the development of postoperative corneal ectasia. We present a case of early onset ectasia after LASIK, review known risk factors in development, and discuss possible strategies for prevention. METHODS A 39-year-old man underwent bilateral LASIK for moderate myopia. Preoperative cycloplegic refractions were -9.00 + 0.25 x 140 degrees OD and -7.75 sphere OS. Corneal topography demonstrated mild inferior steepening bilaterally although definite evidence of keratoconus by either the Klyce/Maeda and Smolek/Klyce keratoconus screening tests was not present. Following the creation of flaps with 160-microm plates, ablations of 93 microm OD and 80 microm OS were performed, estimated to leave residual stromal beds of at least 314 microm OD and 330 microm OS. RESULTS On the first postoperative day, uncorrected visual acuities were 20/400 OD and 20/40 OS. On the fifth postoperative day, the patients uncorrected visual acuity was 20/400 OD, and 20/300 OS. Corneal topography of the right eye showed profound inferior steepening with an apical corneal power in excess of 57 D; topography of the left eye showed mild inferior steepening. Eighteen months after surgery best corrected visual acuity was 20/40 OD and 20/30 OS with rigid gas permeable contact lenses. CONCLUSIONS This case highlights the need for a high index of suspicion when one notes an asymmetric bow-tie pattern on preoperative LASIK corneal topography, despite seemingly safe estimates of residual stromal bed thickness.

Effect of Mitomycin C on the Corneal Endothelium When Used for Corneal Subepithelial Haze Prophylaxis Following Photorefractive Keratectomy

PURPOSE To evaluate the potential effect of topical mitomycin C (MMC) on the corneal endothelium of myopic patients undergoing photorefractive keratectomy (PRK). METHODS Sixteen eyes with a planned ablation depth >75 microm underwent PRK followed by 0.02% MMC applied for 12 seconds using a methylcellulose sponge. Endothelial specular microscopy was performed with the Keeler-Konan specular photomicroscope in 16 eyes before and at least 1 year after surgery. Mean follow-up was 18 months (range: 12 to 24 months). Mean cell density, coefficient of variation of mean cell area, and percentage of hexagonal cells were measured and calculated using computerized morphometric analysis. RESULTS Mean endothelial cell densities before and after surgery were 2882 +/- 783 cells/mm2 (range: 1511 to 4022 cells/mm2) and 2867 +/- 588 cells/mm2 (range: 1638 to 3881 cells/mm2), respectively (P > .05). Mean coefficient of variation before and after surgery was 0.30 +/- 0.07 (range: 0.23 to 0.49) and 0.26 +/- 0.04 (range: 0.22 to 0.33), respectively (P=.06). Mean percentage of hexagonal cells before and after surgery was 61% +/- 6.8% (range: 47% to 70%) and 66% +/- 6.7% (range: 54% to 75%), respectively. CONCLUSIONS Administration of MMC for haze prophylaxis following PRK did not have a significant effect on quantitative endothelial cell density or qualitative morphometric parameters in this study.

Transepithelial phototherapeutic keratectomy/photorefractive keratectomy with adjunctive mitomycin-C for complicated LASIK flaps

Purpose: To evaluate the efficacy of transepithelial phototherapeutic keratectomy/photorefractive keratectomy (PTK/PRK) with prophylactic mitomycin‐C for the treatment of refractive errors and maintenance of corneal clarity following flap complications in laser in situ keratomileusis (LASIK). Setting: Outpatient tertiary care center, Chicago, Illinois, USA. Methods: Ten eyes of 10 patients with LASIK flap complications had transepithelial PTK/PRK for correction of ametropia. Mitomycin‐C 0.02% was applied to the stroma for 2 minutes following laser ablation. Postoperative uncorrected visual acuity (UCVA), best spectacle‐corrected visual acuity (BSCVA), refractions, and slitlamp examinations were obtained. Results: Preoperatively, the mean UCVA was 20/400 (range 20/40 to counting fingers), the mean BSCVA was 20/28.5, and the spherical equivalent refractive errors ranged from +4.00 to −10.75 diopters (D). After the procedure, the mean UCVA was 20/28, the mean BSCVA was 20/21, and the spherical equivalent refractive errors ranged from +0.37 to −1.00 D. The mean follow‐up ranged from 8 to 28 months. No patient experienced delayed reepithelialization, haze, or other signs of toxicity. Conclusion: Mitomycin‐C can be a useful adjunctive therapy for the prevention of haze when applying surface excimer laser therapy to a cornea following LASIK flap complications.

Delayed keratitis after laser in situ keratomileusis

We report 2 cases of delayed keratitis that occurred after uneventful laser in situ keratomileusis (LASIK). The first patient presented with a peripheral corneal infiltrate 3 months after a LASIK enhancement procedure. The infiltrate progressed despite treatment with topical combination tobramycin-dexamethasone. The flap was then lifted and the interface was irrigated with fortified antibiotics. The keratitis promptly resolved, and the patient recovered a best corrected visual acuity (BCVA) of 20/20. The second patient presented with decreased vision, inflammation, and a sublamellar infiltrate 1 month after primary LASIK. The flap was promptly lifted and irrigated with antibiotics. Cultures were positive for Staphylococcus epidermidis. One week later, the infiltrate had resolved and BCVA had returned to 20/20. Delayed bacterial keratitis has been described as a rare occurrence after incisional refractive surgery. To the best of our knowledge, it has not yet been reported after LASIK. It is important to consider infectious keratitis in the differential diagnosis of a patient who presents with corneal inflammation, even months after having LASIK.

Interleukin-2 Induces Corneal Neovascularization in A/j Mice

Mitogen-stimulated lymphocytes induce a highly reproducible form of corneal neovascularization (CNV) in inbred mice. To determine if supernatants derived from stimulated lymphocytes and their constituent mediators were also angiogenic, we injected conditioned medium (CM) from mitogen-stimulated lymphocytes, control non-conditioned medium, recombinant interleukin-2 (rIL-2), or control bovine serum albumin (BSA), a component of rIL-2, into the corneas of syngeneic A/J mice. Control, nonconditioned medium was not angiogenic. While the other injections all induced some CNV, the CM and rIL-2 both induced a significantly greater area of CNV than BSA (p < 0.05). The area of CNV induced by the CM was greater than that induced by IL-2 (p = 0.03). These data show that IL-2, which stimulates vascular endothelial cells in vitro and is elaborated during corneal immune reactions in vivo, is one of the potential mediators of immunologically mediated CNV.

Reduced Application Time for Prophylactic Mitomycin C in Photorefractive Keratectomy

OBJECTIVE To determine whether the duration of mitomycin C (MMC) 0.02% application affects visual outcome or the incidence of subepithelial haze in patients undergoing photorefractive keratectomy (PRK) with prophylactic administration of MMC. DESIGN Retrospective, comparative case series. PARTICIPANTS Two hundred sixty-nine eyes undergoing PRK. METHODS This was a retrospective comparative case series that included 269 eyes that underwent PRK with prophylactic MMC application for 120 seconds (group 1, n = 74), 60 seconds (group 2, n = 36), or 12 seconds (group 3, n = 159). The mean preoperative spherical equivalent was -6.49 diopters (D) in group 1, -6.77 D in group 2, and -7.10 D in group 3. Photorefractive keratectomy was performed using a modified nomogram. All eyes received a single intraoperative application of MMC (0.02%) after laser ablation for the above specified durations. MAIN OUTCOME MEASURES Best-corrected visual acuity and corneal haze score. RESULTS Best-corrected visual acuity was 20/23 in group 1, 20/20 in group 2, and 20/21 in group 3. The mean haze score+/-standard deviation (scale, 0.00-4.00) was 0.11+/-0.31 in group 1, 0.14+/-0.28 in group 2, and 0.07+/-0.20 in group 3 throughout a mean follow-up of 31 months in group 1, 16 months in group 2, and 10 months in group 3. No eyes had a haze score of more than 1.00. CONCLUSIONS There was no statistically significant difference in postoperative best-corrected visual acuity or haze scores among the 3 groups. Administration of prophylactic MMC 0.02% for 12 seconds after PRK seems to be equally efficacious for haze prophylaxis when compared with longer application times of 60 and 120 seconds.

Photodynamic therapy for corneal neovascularization.

We have previously described corneal neovascularization (CNV) induced by the intrastromal injection of interleukin- 2 (IL-2) in inbred mice. Photodynamic therapy (PDT), administered by a deeply penetrating 630 nm fiberoptic laser, can destroy neoplasms and their associated neovascularization with some selectivity, but can damage neighboring tissues when used for CNV. We performed PDT with a 514 nm ophthalmic argon laser in an attempt to induce regression of CNV and reduce the associated toxicity. Eight weeks following IL-2 injection, mice with CNV were injected i.v. with dihematoporphyrin ether (DHE). Seventy-two hours later, 11 eyes (group I) were irradiated with eight 800 mW, 1000 µ, 2 s spots. Controls included 11 vascularized corneas from mice that received DHE but no laser (group II), 11 that received laser but no DHE (group III), and 35 untreated vascularized corneas (group IV). Comparison of the mean areas of CNV in groups I through IV pretreatment (6.0, 6.5, 6.7, and 7.6 mm2) and 12 weeks posttreatment (4.3, 6.3, 5.6, and 7.5 mm2) revealed that a significant decrease was seen in group I only (p<0.04, ANOVA). Complications in group I included blepharitis (9%) and iris damage (18%). Histo- Iogic studies revealed no evidence of posterior segment damage. PDT with the 514 nm laser is safe and efficacious for the treatment of IL-2-induced CNV in this model.