Laser in situ keratomileusis versus photorefractive keratectomy: an update on indications and safety.
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Biomedical subjects
Publications and source records attributed to D T Azar.
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We reviewed papers published in peer-reviewed journals describing techniques and results of laser in situ keratomileusis (LASIK) and summarized the instruments used, nomograms, preoperative and postoperative refractions, predictability, outcome, safety, and complications. We performed a similar review of abstracts published in the abstract books of the 1996 meeting of the International Society of Refractive Surgery, the 1997 meeting of the Association for Research in Vision and Ophthalmology, and the 1997 meeting of the American Society of Cataract and Refractive Surgery. The number of LASIK and photorefractive keratectomy (PRK) patients described in the abstracts were sorted by city. Mean weighted latitudes were calculated and compared for each procedure. The mean preoperative refraction in the papers was -12.59 diopters (D), which was statistically higher than that in the abstracts, -8.71 D (P < .001), and the mean postoperative refraction, -1.10 and + 0.93 D, respectively. The mean percentage of cases within +/- 1.00 D was 67.0% in the papers and 82.5% in the abstracts. Uncorrected visual acuity (UCVA) of 20/40 or better was achieved in 49.2% of eyes in the papers and 83.2% of those in the abstracts; a UCVA of 20/20 or better was achieved in 22.0 and 56.6%, respectively. The portion of eyes that lost two or more lines of best corrected visual was 8.0% in the papers and 0.9% in the abstracts. Complications in the papers included irregular flap (4.0%), incomplete cut (2.5%), free cap (4.9%), perforated lenticule (2.6%), short flap (3.0%), sliding flap (1.4%), interface debris (6.8%), central island (5.3%), decentration (4.7%), epithelial ingrowth (4.3%), induced astigmatism (5.1%), wrinkles (5.9%), haze (8.7%), night vision problems (14.0%), and reoperation (8.2%), Mean latitude for LASIK cases (27.00 degrees +/- 13.73 [SD] was significantly lower than that for PRK cases (42.85 +/- 11.7 degrees). Visual outcomes of LASIK surgery show significant improvements when recent abstracts are compared with published papers. This may reflect continued improvement in the surgical techniques, surgeons' skills, and visual outcomes.
OBJECTIVE: To correlate corneal light scattering with keratocyte and extracellular matrix reformation after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). SETTING: Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland, USA. METHODS: Sixteen pigmented rabbit eyes were randomly divided into 2 groups. Group 1 (n = 8) had a 5.0 mm, -10.0 diopter (D) LASIK treatment and Group 2 (n = 8), a 5.0 mm, -10.0 D surface PRK treatment after mechanical epithelial debridement. The stromal surface exposed at surgery was stained with dichlorotriazinylaminofluorescein (DTAF) solution. Slitlamp biomicroscopic and objective measurement of corneal light scattering using a scatterometer were performed 1 and 2 days and 1, 2, 3, 4, 8, and 12 weeks after surgery. In each group, 2 corneas were harvested at 1 week and 1 month and 4 corneas were harvested at 12 weeks. Tissue sections were examined by light and fluorescence microscopy. The percentage of newly formed stromal tissue was calculated and correlated with the scatterometry index. RESULTS: In Group 1, corneas remained clear and healed without significant scarring throughout the study. In Group 2, subepithelial scarring was noted. Extracellular matrix reformation peaked at 1 month and showed a slight regression thereafter. The percentage of extracellular matrix reformation was strongly correlated with the scatterometry index (r = .86, P < .001). CONCLUSIONS: In this study, significant subepithelial stromal tissue reformation followed PRK. The percentage of extracellular matrix reformation correlated well with the objective corneal light scattering measurements.
PURPOSE: To evaluate the visual outcomes in patients having photorefractive keratectomy (PRK) to correct residual myopia after radial keratotomy (RK). SETTING: Nine refractive surgery centers in the United States and one in South Korea. METHODS: This retrospective analysis comprised 38 eyes of 32 patients treated with PRK after RK and followed for 12 months. Analysis was based on pre-RK and pre-PRK refraction as well as response to RK (pre-RK minus pre-PRK refractions). RESULTS: Mean pre-RK and pre-PRK refractions were -8.11 diopters (D) +/- 2.92 (SD) and -4.28 +/- 2.08 D, respectively. One month after PRK, mean refraction was +0.42 +/- 1.56 D and regressed to -0.95 +/- 1.24 D at 12 months. At 12 months, 65% of eyes had an uncorrected visual acuity of 20/40 or worse, and 11.1% lost 2 or more lines of best corrected acuity. Of eyes with an original erro of -6.00 or less, 81.8% were within +/- 1.00 D of intended correction at 12 months and of those with an original error of -9.12 to -20.00 D 50.0% (P = .004). All eyes with residual (pre-PRK) errors of -3.00 D or less and 42.9% with a residual error of -6.12 to -9.00 D were within +/- 1.00 D of intended correction (P = .07). There were no statistically significant differences in the response to PRK between eyes that had an RK response of 0 to 3.00, 3.12 to 6.00, or 6.12 to 12.00 D. CONCLUSION: Patients with lower original and residual myopia achieved better visual outcomes after PRK than those with higher myopia. The amount of myopic correction achieved using RK was not predictive of the amount of myopic correction using PRK.
PURPOSE: To determine the expression of gelatinases A and B and the localization of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 during the early stages of corneal wound healing in rats. METHODS. One eye each of 30 adult Sprague-Dawley rats was treated with excimer laser keratectomy; the other eye was untreated. Frozen sections of corneas obtained 6, 18, and 24 hours and 3 and 7 days after wounding were used to perform immunoconfocal microscopy and in situ hybridization. RESULTS: Gelatinase B was immunolocalized to the basement membrane zone and superficial stroma, and its mRNA was exclusively localized to basal epithelial cells migrating across the wound at 18 and 24 hours and 3 days after wounding. Tissue inhibitor of metalloproteinase-1 was also immunolocalized to the basement membrane zone and superficial stroma at the same time points. Gelatinase A was immunolocalized to the epithelium and stroma of normal corneas and was predominant in the basal epithelium and superficial stroma at 3 and 7 days after wounding. In situ hybridization confirmed gelatinase A expression by the epithelial cells and the stromal keratocytes. Tissue inhibitor of metalloproteinase-2 was immunolocalized to the epithelium in normal and wounded corneas. Intense TIMP-2 labeling of the basement membrane zone was noted 3 days after wounding. CONCLUSIONS: Unlike gelatinase A, gelatinase B is expressed exclusively by migrating basal epithelial cells after wounding. The matrix metalloproteinase-tissue inhibitor of metalloproteinase (MMP)/TIMP systems may play an important role in the early stages of corneal wound healing after excimer laser keratectomy.
PURPOSE: Intrastromal epithelial migration occurs following deep excimer annular keratectomy. Our purpose is to determine the localization of gelatinase B expression and its relationship to migrating intrastromal epithelial cells following deep annular excimer keratectomy. METHODS: Rabbit corneas were treated with deep annular ablation and harvested 3, 5, 7 and 14 days following surgery. Histological examination was performed. Confocal microscopy was used to determine the time and the pattern of gelatinase B expression. This was compared to AE-5, vimentin, and alpha-smooth muscle actin immunolocalization. RESULTS: Histologic examination revealed islands of epithelial cells within the corneal stroma after deep annular excimer ablation, whereas eyes treated with superficial annular keratectomy did not show intrastromal epithelial migration. Immunoconfocal microscopy using monoclonal anti-matrix metalloproteinase-9 (MMP-9) antibody demonstrated the presence of gelatinase B at the outer borders of the intrastromal epithelial islands following deep annular excimer keratectomy. CONCLUSION: Gelatinase B may be involved in the process of intrastromal epithelial migration following deep annular excimer keratectomy.
PURPOSE: To evaluate treatment displacement and movement during treatment (drift) after excimer laser photorefractive keratectomy using tangential topographic maps. METHODS: Forty-eight eyes of 48 patients showing axial decentration of 0.30 mm or more at 1 month posttreatment were reevaluated retrospectively to determine treatment displacement of the center of the photorefractive keratectomy ablation from the center of the pupil. A drift index was calculated to determine the relative degree of movement (drift) during treatment. We subdivided patients into four groups based on the degree of treatment displacement and drift and compared the mean axial decentration and the mean best-corrected logMAR visual acuity among the subgroups. RESULTS: Mean treatment displacement +/- SD from the center of the entrance pupil was 0.34 +/- 0.21 mm. Thirty-eight eyes (79.2%) had ablations within 0.50 mm from the center of the entrance pupil. We observed downward displacement in 27 eyes (56.2%) and upward displacement in 21 eyes (43.8%). The drift index showed a positive, statistically significant correlation with best-corrected visual acuity (r = .58, P < .0001). Patients with low displacement and low drift had mean logMAR best-corrected visual acuity of 0.91, which was statistically significantly better than patients with high displacement and high drift (r = 0.64; P = .009). CONCLUSIONS: In patients with gross decentration by axial topography after photorefractive keratectomy, tangential corneal topography is valuable in evaluating and differentiating photorefractive keratectomy treatment displacement from movement during treatment (drift). Patients with high drift index have worse visual outcomes after photorefractive keratectomy than those exhibiting high treatment displacement.
OBJECTIVE: The purpose of the study is to compare alcohol-assisted versus mechanical debridement of the corneal epithelium before photorefractive keratectomy (PRK) for low-to-moderate myopia. DESIGN: A prospective study was performed on a group of consecutive patients operated on at the Massachusetts Eye and Ear Infirmary from February to April 1996 and followed for 6 months. PARTICIPANTS: Eighty patients (eyes) were divided in 2 groups: 40 alcohol and 40 mechanical. INTERVENTION: The patients underwent PRK for myopia (-1.5 to -7.5 diopters) with a Summit Apex excimer laser. The corneal epithelium was removed either with 20% ethanol or with a scalpel blade. MAIN OUTCOME MEASURES: The two groups were compared for epithelial removal time, epithelial defect size at the end of surgery, and rate of re-epithelialization. Uncorrected visual acuity (UCVA), refractive outcome, best-corrected visual acuity (BCVA), and subjective haze were measured at 4 days and at 1, 3, and 6 months. In an additional short-term study, 40 patients (20 alcohol, 20 mechanical) had intraoperative pachymetry performed. RESULTS: Alcohol-assisted de-epithelialization was faster than mechanical debridement (107 [+/-20.6 standard deviation] versus 141 [+/-30.5] seconds [P < 0.0001]) and led to a more circumscribed and reproducible epithelial defect at the end of surgery (87,739 [+/-11,852] versus 103,518 [+/-33,942] square pixels [t test, P = 0.04; f test, P = 0.001]). At 4 days, 95% of the alcohol-treated patients had healed compared with 78% of the mechanically scraped patients (Fisher's exact test, P = 0.04). The alcohol group had a better UCVA at 4 days (logarithm of the minimum angle of resolution UCVA 0.36 [+/-0.22] versus 0.51 [+/-0.26]) and at 1 month (0.14 [+/-0.17] versus 0.22 [+/-0.16] [Mann-Whitney U test, P = 0.02 and P = 0.03]) but equalized at 3 months (0.10 [+/-0.14] versus 0.13 [+/-0.16]) and at 6 months (0.11 [+/-0.15] versus 0.14 [+/-0.13] [Mann-Whitney U test, P = 0.23 and P = 0.34]). There was a trend toward less subjective haze in the alcohol-treated patients over the course of the study (area under the curve, 71.9 [+/-35.3] versus 87.9 [+/-33.8] [Mann-Whitney U test, P = 0.07]). The difference from target was equivalent in both groups at 6 months (-0.22 [+/-0.58] diopter in the alcohol group and -0.43 [+/-0.52] diopter in the mechanical group [t test, P = 0.14; f test, P = 0.57]). There were no differences in intraoperative pachymetry, corneal uniformity index as calculated from the corneal topography, and loss of BCVA between the two groups. CONCLUSIONS: Twenty percent ethanol is a simple, safe, and effective alternative to mechanical scraping before PRK and appears to be associated with a quicker visual rehabilitation.
PURPOSE: To compare surgically induced astigmatism and visual outcomes after three-, one-, and no-suture phacoemulsification. SETTING: Johns Hopkins Hospital, Baltimore, Maryland and Manhattan Eye, Ear, and Throat Hospital, New York, New York, USA. METHODS: This prospective, randomized study followed 131 patients treated with phacoemulsification with a 5.5 mm self-sealing scleral tunnel and implantation of a 5.5 mm poly(methyl methacrylate) posterior chamber lens. Radial 10-0 nylon sutures were used in the three- and one-suture groups. RESULTS: Mean astigmatism was greatest in the first postoperative week in all groups and stabilized after 8 weeks. The percentage of patients with with-the-rule (WTR) astigmatism increased from baseline in the one- and three-suture groups and decreased in the sutureless group. Mean uncorrected Snellen acuity was significantly better in the no- and one-suture groups than in the three-suture group at 1 week. There were no significant differences in uncorrected acuity at other times. No statistically significant differences in the surgically induced spherical equivalent were noted among the three groups during the 1 year follow-up. There was significantly less surgically induced keratometric astigmatism in the one-suture group at 4 (P = .03) and 8 (P = .007) weeks postoperatively. At all follow-ups, the sutureless group had the greatest proportion of patients, with significant ATR astigmatic shift (1 week, 17%; 4 weeks, 32%); and the lowest proportion of patients with significant WTR astigmatic shift (10% after 1 week). At 4 weeks, the percentage of patients with significant WTR shift in the one-suture group dropped to that in the sutureless group (10%); however, those in the one-suture group had less ATR astigmatic shift (16%). CONCLUSION: Sutureless and one-suture surgery resulted in a low percentage of WTR induced astigmatism 4 weeks postoperatively. Compared with sutureless surgery, the one-suture surgery resulted in less ATR shift.
PURPOSE: To obtain objective measurements of corneal light scattering after excimer laser keratectomy, and to evaluate the relation of light scattering to clinical haze grading and visual acuity. METHODS: The authors measured best-corrected visual acuity, subjective clinical haze grade, and corneal light-scattering index in patients undergoing photorefractive keratectomy (PRK) (n=26), and phototherapeutic keratectomy (n=8), preoperatively and postoperatively at 1,3,6,9, and 12 months or later. Corneal light scattering was correlated with visual acuity and clinical haze grade. RESULTS: Corneal light scattering increased after PRK and was reduced after phototherapeutic keratectomy. Corneal light scattering index showed a stronger positive correlation with logMAR visual acuity (r=0.57) than clinical haze grading (r=0.34). Corneal light-scattering index (P<0.05 at 1 and 3 months) and clinical haze grading (P<0.05 at 6, 9, and 12 months) were significantly higher in eyes undergoing PRK with ablation depths of more than 80 microns. CONCLUSIONS: Excimer laser surgery affects corneal light scattering. Ablations with depths greater than 80 microns produce significantly higher levels of haze than those less than 80 microns. Objective measurement of corneal light scattering may be useful in monitoring the outcome of excimer keratectomy.
The purpose of this study was to evaluate corneal reepithelialization and wound healing following annular excimer keratectomy. Two sets of experiments were performed on 35 rabbit eyes. In the first set of experiments, experiment I, deep Fresnel excimer keratectomy was performed, with a 6-mm outer and 3-mm inner diameter. Animals were sacrificed at 1, 5, 12, and 16 weeks, and corneas were examined by light and electron microscopy. In experiment II, the central epithelium was left intact, and superficial and deep mid-peripheral excimer annular keratectomies were performed measuring 6 mm in outer and 3 mm in inner diameter. Animals were sacrificed at 1 week, and corneas were examined by light microscopy. Following deep Fresnel excimer keratectomy (experiment I), corneas showed stromal edema in the central 3-mm zone. Intrastromal islands of epithelial cells with PAS positive basement membrane-like structures were seen histologically at 1 week. Electron microscopy showed loss of stromal collagen in areas adjacent to epithelial islands; in areas distant from the epithelial islands, the stromal collagen appeared normal. The overlying central stroma sloughed after 5 weeks. Anterior stromal scarring was observed. In experiment II (mid-peripheral annular keratectomy), intrastromal epithelial accretion was present in corneas with deep annular keratectomy but not in superficial annular keratectomy. Intrastromal epithelial accretion follows deep excimer annular keratectomy and is associated with adjacent stromal degradation.
To determine the expression of matrix metalloproteinases (MMPs) in cornea following excimer laser keratectomy, two sets of experiments were performed. In the first experiment, disciform excimer keratectomy was performed on rat corneas. The central regenerating epithelium was harvested at 3-96 h postwounding. MMP levels were assayed in the regenerated central epithelium and the stroma using zymography and immunoblot assays. In the second set of experiments, deep excimer annular keratectomy was performed on rabbit corneas to induce intrastromal epithelial migration. The effect of beta-mercaptomethyl tripeptide, a synthetic inhibitor of metalloproteinase, on the presence and extent of intrastromal epithelial migration was determined. In experiment I, MMP-2 and MMP-9 were expressed in the epithelium of excimer-ablated rat corneas 6-24 h postwounding, but not in the debridement wounds and untreated controls. Only excimer-treated stroma showed MMP-9 activity. In experiment II, intrastromal epithelial migration was delayed by topical application of beta-mercaptomethyl tripeptide, a synthetic inhibitor of MMPs (p < 0.05). After excimer wounds, MMPs are expressed in corneal epithelium and stroma during wound closure. They may play an important role in wound healing after excimer laser keratectomy.
BACKGROUND AND OBJECTIVE: Excimer laser-corneal tissue interaction liberates highly reactive free radicals. Our aim was to determine if intraoperative application of antioxidants reduces the postoperative corneal light scattering by minimizing free radical-mediated cellular injury. STUDY DESIGN/MATERIALS AND METHODS: Phototherapeutic keratectomy (PTK) was performed in 20 rabbit eyes. Following 40-microns epithelial ablation, rabbits were divided into two groups and received 1-minute intraoperative application of either 50% dimethyl sulfoxide and 1% superoxide dismutase or vehicle (balanced salt solution) only. This was followed by a 6-mm diameter 100-microns PTK. Corneal light scattering was measured for 18 weeks using scatterometry. A light scattering index (SI) ranging from 0-10 was calculated; SI = 1 represents normal scattering. Light microscopic examination was performed in selected corneas. RESULTS: The mean baseline SI was similar for both groups (P = 0.95). Corneal haze followed a pattern of gradually increasing to peak at 2-3 weeks, and regressing partially thereafter. The decrease in mean SI following antioxidant application (dimethyl sulfoxide and superoxide dismutase) as compared to control group approached significance at 3 weeks (0.1 > P > 0.05) and was highly significant at 9 weeks (P < 0.05). CONCLUSION: Intraoperative application of antioxidants decreases light scattering following excimer keratectomy in rabbit corneas. UV-induced free radicals may play a role in the pathogenesis of corneal light scattering following excimer laser keratectomy.
PURPOSE: To compare corneal light scattering after laser in situ keratomileusis and photorefractive keratectomy in rabbit eyes. METHODS: For laser in situ keratomileusis, a 5-mm, -10-diopter spherorefractive resection was performed on the stromal bed under a corneal flap. Corneal light scattering was objectively measured for 12 weeks, and compared to corneal light scattering after photorefractive keratectomy (5 mm, -10 diopters). RESULTS: Corneal light scattering was significantly lower in the laser in situ keratomileusis group than in the photorefractive keratectomy group at all time points after surgery (P < .01 at weeks 1 through 6, and P = .03 at week 12). CONCLUSIONS: In this experimental study, laser in situ keratomileusis resulted in significantly less corneal light scattering than photorefractive keratectomy.
OBJECTIVE: To determine the pattern of long-term reformation of the adhesion structures after excimer laser phototherapeutic keratectomy. METHODS: Four corneal buttons were removed at penetrating keratoplasty 6 to 15 months after initial excimer laser phototherapeutic keratectomy. Morphometric analysis of electron micrographs of the wound bed was performed to determine the extent and pattern of reformation of hemidesmosomes, anchoring fibrils, and basal laminae. RESULTS: Eight percent of the basal epithelial cells had underlying normal anchoring fibrils at 6 months, compared with 35% at 15 months. The percentage of basal cell membrane occupied by hemidesmosomes remained fairly constant (35.2% to 37.7%). With the exception of a localized area of multilamination seen at 9 months, the cross-sectional area of basal lamina per 100 microns of basal cell membrane increased with the duration of wound healing (18.0 microns 2 at 6 months, 24.4 microns 2 at 15 months) but remained below normal levels (32 microns 2). CONCLUSIONS: These data suggest that after human excimer keratectomy, the anchoring fibrils and basal lamina do not completely normalize even after 15 months.
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OBJECTIVE: To report objective grading and analysis of excimer laser-induced scarring using high-frequency ultrasound. METHODS: High-frequency ultrasound (50 MHz) corneal examination was performed on eight New Zealand white rabbits at different time points (10, 17, 24, and 74 days following phototherapeutic keratectomy). We used biometry and signal-processing techniques to determine corneal, epithelial, and scar thicknesses and to quantify the acoustic backscatter. RESULTS: Excimer laser-induced scarring showed an irregularly distributed acoustic hyperreflectivity that decreased through day 74. Corneal thickness remained reduced after ablation (mean, 318 microns compared with 419 microns for controls). Epithelial thickness averaged 62 microns and scar thickness, 87 microns. Scar peak and average anterior stroma acoustic backscatter ratios decreased from day 10 to day 74 (19.65 to 2.76, and 6.42 to 1.32, respectively). Histopathologic study showed increased keratocyte activity at early time points that correlated with acoustic backscatter ratios and imaging pattern. CONCLUSIONS: High-frequency ultrasound signal processing is a noninvasive method that quantitatively grades excimer laser-induced corneal scarring.
PURPOSE: To understand the underlying mechanisms responsible for the easy removal and sloughing of corneal epithelium in vitamin A deficiency. METHODS: An animal model of vitamin A deficiency, the vitamin A-deficient rat (A-rat), transmission electron microscopy, computer-assisted morphometric analysis and indirect immunofluorescence were used to study the adhesion of rat corneal epithelium to its basement membrane with emphasis on structure and molecular composition of the anchoring structures such as the hemidesmosome and bullous pemphigoid antigen. RESULTS: Transmission electron microscopy resolved numerous microseparations of the basal epithelial cell membrane from the basement membrane with intervening segmental basement membrane duplications and electron dense deposits. Morphometric analysis disclosed a statistically significant reduction in the frequency and size of hemidesmosomes. Four weeks after supplementing the diet with retinyl acetate (700 micrograms/week), significant reversal of these same structural abnormalities could be detected. Immunofluorescence staining for bullous pemphigoid antigen, a component of the adhesion complex, showed intense staining of the basal epithelial cytoplasm but weak and discontinuous staining of the basement membrane. Weak staining for laminin was also evident in A- corneas. In contrast, normal corneas displayed no cytoplasmic staining for bullous pemphigoid antigen and intense staining of the basement membrane for bullous pemphigoid antigen and laminin. CONCLUSIONS: The authors propose that structural abnormalities of the epithelial basement membrane complex are responsible for the observed loose epithelial adhesion and sloughing, as well as other known abnormalities of healing in the vitamin A-deficient rat cornea.