Corneal haze after photorefractive keratectomy using different epithelial removal techniques: mechanical debridement versus laser scrape

PURPOSE: To determine differences of corneal wound healing and haze after photorefractive keratectomy (PRK) using either mechanical epithelial debridement or laser-scrape epithelial removal in human subjects. DESIGN: A 6-month randomized, masked, prospective, paired-eye clinical study. PARTICIPANTS: Twenty eyes in 10 myopic patients treated between March 1999 and May 1999. INTERVENTION: Photorefractive keratectomy treatments with two different epithelial removal techniques. Continuous z-scan of confocal image, termed confocal microscopy through focusing (CMTF), was performed before surgery and at 3 weeks, 6 weeks, 3 months, and 6 months after surgery. MAIN OUTCOMES MEASURES: Epithelial and stromal thickness measurement, achieved stromal ablation depth, and objective assessment of corneal light-backscattering (corneal haze) were obtained from digital image analysis of the CMTF scans. Manifest refraction was also measured. Student's paired t test or two-way repeated-measures analysis of variance after rank transformation were performed to evaluate statistical differences between groups. RESULTS: Comparison of the mean posttreatment spherical equivalent between the two techniques showed no statistically significant difference. In preoperative corneas, mean epithelial thickness was 50.08+/-3.70 microm in the mechanical debridement group and 50.49+/-4.01 microm in laser-scrape group (not significant). For both groups, the epithelium was significantly thinner at 3 weeks, but returned to preoperative values by 6 months, with no difference between groups. Planned stromal ablation depth by PRK was 59.38+/-11.48 microm (39-73 microm; n = 8) in the mechanical group and 57.75 +/- 7.21 microm (48-70 microm; n = 8) in the laser-scrape group. Achieved stromal ablation depth was not significantly different between the two groups. Most importantly, in both groups CMTF-measured corneal haze increased significantly after surgery, peaked at 3 months, and then decreased at 6 months, with no significant difference between groups. (Power = 0.96). CONCLUSIONS: There is no significant difference in the corneal wound healing response between mechanical epithelial debridement versus laser-scrape technique in human myopic eyes undergoing PRK.     

LASIK induces minimal regrowth and no haze development in rabbit corneas

PURPOSE: To quantify central corneal regrowth and haze development after LASIK in rabbits. METHODS: New Zealand White rabbits received an 89 microm (-8 diopters) myopic LASIK and were evaluated during 4 months using slit-lamp and in vivo confocal microscopy to monitor changes in central corneal morphology, epithelial and stromal thickness, flap and bed thickness, and corneal light backscattering (haze). At various time-points, corneas were processed for histology. RESULTS: Using in vivo confocal microscopy, LASIK induced no detectable morphological changes besides a slightly elevated light backscattering at the interface. Correspondingly, all corneas remained clear with no haze development by slit-lamp biomicroscopy. Corneal thickness was stable by 8 weeks after an increase of 17 +/- 4 microm that consisted of a 13 +/- 3 microm stromal regrowth and a 4 +/- 2 microm epithelial hyperplasia. At the LASIK interface, less than 4 microm new extracellular matrix was deposited. Accordingly, all LASIK flaps were easily pulled off by 6 months. CONCLUSIONS: LASIK induces a minimal wound healing response in rabbit corneas with no haze development and a regrowth (regression) of only 17 microm of an 89-microm photoablation. Three main factors contributed to the observed regrowth: epithelial hyperplasia (approximately 4 microm), matrix deposition at the LASIK interface (approximately 4 microm), and stromal growth outside the interface within the flap and wound bed (approximately 9 microm).     

准分子激光角膜切削术与准分子激光原位角膜磨镶术角膜创口愈合的对比实验研究

比较准分子激光角膜切削术(photorefractive keratectomy,PRK)与准分子激光原位角膜磨镶术(1aser in situ keratomileusis,LASIK)后激光对角膜组织的切削效应及角膜的愈合情况,从组织学角度探讨角膜雾状混浊(Haze)及屈光度数回退的成因。方法24只新西兰白兔按预矫屈光度数随机分为-4.00 D组和-8.00 D组,每只兔右眼行PRK,左眼行LASIK。术后10d,1、3及6个月观察Haze情况并验光,每组随机处死3只兔取角膜行光镜、电镜及免疫组化检查,检测胶原Ⅲ、胶原Ⅳ、纤维连结蛋白(fibronectine,FN)及转化生长因子-β(transforming growth factor-β1,TGF-β2)的含量。结果行PRK术的右眼术后出现不同程度的Haze及屈光度数回退,其程度与预矫正屈光度数成正比。行LASIK术的左眼术后除少数角膜瓣周围半环形混浊外,手术区域角膜透明,屈光度数回退较右眼轻。-4.00 D组右眼与左眼术后屈光度数均稳定,-8.00 D组右眼较左眼屈光度数回退明显。右眼术后角膜愈合反应重,恢复慢。6个月时角膜基质仍处于修复阶段。左眼术后除形成角膜上皮栓及对应处基质轻度增生外,手术区域角膜瓣与基质床间界面清晰,无明显增生,角膜基质愈合反应轻、恢复快。术后所有兔眼角膜均有TGF-β1表达及活化,持续时间与角膜愈合时间一致。Haze及屈光度数回退组织学改变为：角膜上皮细胞增生,基底膜不成熟,前基质角膜细胞活化、增殖,新生胶原Ⅲ合成、排列紊乱,细胞外基质FN在角膜上皮下沉积。结论LASIK矫正近视尤其是高度近视优于PRK;角膜伤口愈合特别是基质愈合的反应程度,是。Haze及屈光度数回退的关键;TGF-β1是角膜愈合过程中重要调节因子,可通过介导角膜上皮一基质相互作用,调节胶原Ⅲ及FN的含量,参与瘢痕形成。     

Mitomycin C alters corneal stromal wound healing and corneal haze in rabbits after argon-fluoride excimer laser photorefractive keratectomy.

PURPOSE: To investigate the effects of mitomycin C (MMC) on rabbit cornea wound healing after photorefractive keratectomy (PRK). MATERIALS AND METHODS: Rabbit corneas were stained with dichlorotriazinyl aminofluorescein immediately after PRK. MMC was applied to the right eye and phosphate-buffered salt solution (PBS) to the left. Corneal epithelial wound healing rate and corneal haze were examined. Ultrasound pachymetry was performed. Stromal collagen regeneration was evaluated by fluorescent microscopy. We used terminal deoxyribonucleotidyl transferase-mediated D-uridine 5'-triphosphated-digoxigenin nick-end labeling (TUNEL) assay and transmission electron microscopy (TEM) to evaluate keratocyte apoptosis. RESULTS: In eyes treated with MMC, there was no delay to the healing rate of corneal epithelial wound, and less haze 4 weeks after PRK. Ultrasound pachymetry showed thinner corneal thickness in MMC-treated eyes at week 4. Corneal stromal thickness regression was less in MMC-treated eyes observed by fluorescent microscope at week 4. Keratocyte apoptosis was noted in both MMC- and PBS-treated eyes by TUNEL assay and TEM observation. This study discovered the phenomenon that MMC prolongs keratocyte apoptosis. CONCLUSIONS: Applying MMC after PRK is an effective method to decrease haze formation and corneal stromal thickness regression in rabbit corneas. The effect may be related to MMC prolonging keratocyte apoptosis.     

Changes in central corneal thickness after laser in situ keratomileusis and photorefractive keratectomy

PURPOSE: To evaluate changes in corneal thickness after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) in eyes with the same preoperative refraction, correlate these changes to postoperative refractive outcomes, and compare corneal healing process in a standardized subset of patients. METHODS: Central corneal thickness was measured by contact ultrasound pachymetry in 14 eyes of 8 patients with preoperative myopia of -6.00 D who had LASIK, and in 14 eyes of 8 patients with the same preoperative refractive error who had PRK. Measurements were taken preoperatively, and 1 week, 3, and 6 months after surgery. Data were evaluated and compared using the paired Student t-test and Pearson correlation coefficient. RESULTS: Mean preoperative central corneal thickness in the LASIK group was 549.14 +/- 37.4 microm, and in the PRK group, 552.64 +/- 34.9 microm. At 1-week postoperatively, mean central corneal thickness in the LASIK eyes was 467.28 +/- 29 microm and in the PRK eyes, 473.85 +/- 39.2 microm; at 6 months, central corneal thickness had increased in both groups compared to the 1-week values; LASIK eyes had a mean central corneal thickness of 481.42 +/- 23.0 microm and PRK, 481.50 +/- 35.3 microm. Mean postoperative refraction after 6 months was -0.48 +/- 0.30 D in the LASIK group and -0.67 +/- 0.35 D in the PRK group. CONCLUSION: Increase in central corneal thickness between 1 week and 6 months postoperatively occurred in both LASIK and PRK eyes, but differences were not statistically significant. No statistically significant differences were found in myopic regression between the two patient groups.     

LASEK and photorefractive keratectomy for myopia: clinical and confocal microscopy comparison

PURPOSE: To compare postoperative visual acuity and corneal morphology after laser epithelial keratomileusis (LASEK) versus photorefractive keratectomy (PRK) in the correction of low to moderate myopia. METHODS: In a double-blind, randomized clinical trial, 50 myopic patients (mean: -4.5 +/- 1.35 diopters) were randomized to receive LASEK in one eye and PRK in the fellow eye. No mitomycin C eye drops were used in this study. Patients were observed daily for 4 days, then at 1 month and every 3 months up to 1 year. Uncorrected and best-corrected visual acuity (UCVA and BSCVA), manifest refraction, corneal epithelium healing time, postoperative pain, and corneal haze were evaluated. Corneal wound healing was quantified with corneal confocal microscopy. RESULTS: Refractive error, UCVA, and BSCVA were not statistically different between eyes treated with LASEK and PRK. Corneal epithelium healing time was 2.52 +/- 0.99 days in the eyes treated with PRK and 2.29 +/- 0.52 days in the eyes treated with LASEK (P=.22). The postoperative pain score was 2.17 +/- 0.87 in the eyes treated with PRK and 2.62 +/- 0.60 (P=.02) in the eyes treated with LASEK. Corneal confocal microscopy showed fewer stromal activated keratocytes and less extracellular matrix deposition in the eyes treated with LASEK than in the eyes treated with PRK at 1 month postoperatively (P=.003). CONCLUSIONS: LASEK is an effective and safe procedure for low to moderate myopia, but it seems more painful until full corneal reepithelization. In the early postoperative period, the corneal wound healing process is significantly less intense in eyes treated with LASEK than in eyes treated with PRK. The role of LASEK in corneal wound healing modulation remains controversial.     

Role of keratocyte loss on corneal wound repair after LASIK

PURPOSE: To investigate whether an initial keratocyte loss intensifies central corneal wound repair after LASIK in rabbits. METHODS: New Zealand White rabbits received either conventional LASIK (-8 D, 6-mm diameter) or LASIK combined with a 7-mm diameter, epithelial denudation (LASIK-scrape). Animals were examined during 4 months by slit lamp and in vivo confocal microscopy to monitor changes in central corneal morphology, light backscattering (haze), and sublayer thickness. At various time points, corneas were processed for histology and stained for nuclei; F-actin; ED-A fibronectin; alpha-smooth muscle actin; TGF-beta1, -beta2, and -beta receptor II; and connective tissue growth factor (CTGF). RESULTS: In vivo confocal microscopy identified no major acellular zones or changes in cell morphology or reflectivity after conventional LASIK. By contrast, a complete loss of keratocytes was observed in the anterior 77 +/- 25 microm stroma 1 week after LASIK-scrape. Highly reflective, migratory fibroblasts gradually repopulated the acellular zone, and by week 8, quiescent-appearing keratocytes were observed throughout the stroma. Correspondingly, stromal light backscattering peaked at 2 weeks after LASIK-scrape (2200 +/- 620 U) followed by a decline to approximately 60 U from week 8; comparable to the slightly increased reflectivity (approximately 50 U) observed after conventional LASIK (ns). Stromal thickness appeared stable 8 weeks after both LASIK and LASIK-scrape, after a regrowth of 13 +/- 3 and 20 +/- 11 microm, respectively (ns). In addition, both procedures induced a minor and comparable epithelial hyperplasia of 4 +/- 2 and 7 +/- 5 microm, respectively (ns). No myofibroblast transformation or TGF-beta growth factor expression was observed below the flap after either treatment. CONCLUSIONS: LASIK-scrape induces an anterior keratocyte loss, leading to development of temporary haze during cell repopulation. However, 8 weeks after both LASIK and LASIK-scrape, only a slightly increased reflectivity is noted at the interface. Corneal thickness is stable by week 8, and stromal regrowth and epithelial hyperplasia are comparable after both treatments. Thus, an initial loss of stromal keratocytes does not appear to intensify corneal wound repair after LASIK.     

Evaluation of photorefractive keratectomy retreatments after regressed myopic laser in situ keratomileusis

PURPOSE: To evaluate the results of photorefractive keratectomy (PRK) enhancements in eyes previously treated by myopic laser in situ keratomileusis (LASIK) showing an undercorrection due to either a refractive regression or a primary undercorrection, when an in-the-bed enhancement was not advisable because of residual stromal thickness limitations. DESIGN: Noncomparative, prospective, interventional case series. PARTICIPANTS: Seventeen eyes of 17 patients previously treated by LASIK for a spherical equivalent (SE) correction of -8.125 to -12.50 diopters (D; mean, -9.45 +/- 1.01 D), that after a follow-up of 6 to 14 months ended up with a refraction of -1.50 to -3.75 D (SE; mean, -2.48 +/- 0.74 D). Intended flap thickness was 160 microm for all eyes. In all cases, the residual stromal bed under the flap was considered too thin (255-305 microm) to allow an in-the-bed enhancement without exceeding an assumed safety thickness limit (250 microm). INTERVENTION: Eyes were treated by PRK at least 6 months after LASIK. The PRK ablation parameters (diameter, attempted correction) were selected to avoid theoretical flap perforation. The deepest ablation was 60 microm, for a -3.75-D correction. We used a Bausch & Lomb 217 C excimer laser (Bausch & Lomb, Rochester, New York). MAIN OUTCOME MEASURES: Refraction, uncorrected and best-corrected visual acuity (BCVA), slit-lamp evidence of corneal opacity or other visible complications, and corneal topography. RESULTS: Although the initial postoperative period was characterized by very satisfactory refractive results (mean SE error at 1 month, -0.04 +/- 0.37 D; range, +0.75 to -0.625 D), during follow-up, a dense haze (grade 3 and 4) developed in 14 eyes (82.3%) that induced a further myopic regression (SE, -1.725 to -5.50 D; mean, -3.11 D) and BCVA loss (two to six lines). These 14 eyes underwent a further surgical treatment to remove the severe haze at 3 to 10 months after PRK. CONCLUSIONS: Based on these results, we strongly advise against PRK as a possible option to correct eyes previously treated by myopic LASIK that resulted in an undercorrection.     

Thermal consequences of photorefractive keratectomy.

PURPOSE: Photorefractive keratectomy (PRK) is still a widely used method for the correction of refractive error despite the advent of laser in situ keratomileusis (LASIK). However, both procedures are associated with significant side effects such as corneal haze and regression. Several factors have been implicated in the etiology of haze, one of which is thermal loading of the cornea. The purpose of this study was to investigate the temperature changes occurring during PRK when performed at different ablation depths. METHODS: Noncontact, color-coded ocular thermography was performed with an infrared detector apparatus during PRK ablation on 19 ovine corneas. Five different refractive corrections were carried out ranging from -2.00 diopters (D) (ablation depth, 31.2 microm) to -10.00 D (ablation depth, 137.9 microm). RESULTS: A temperature rise at the corneal surface was demonstrated in all 19 corneas. The mean rise in temperature was 7.35 +/- 1.13 degrees C with a maximum rise in temperature of 8.97 degrees C. A positive correlation was found between the refractive correction and the peak rise in temperature (r2 = 0.57, p< 0.0001). The rate of temperature change was greater for smaller treatments than for larger treatments (r2 = 0.79, p < 0.0001). Corneas undergoing larger treatments were subject to greater rises in temperature for longer periods of time. CONCLUSIONS: This study suggests that the cornea undergoes a significant rise in temperature as a result of the PRK process. Further investigation is required to determine what effect this thermal loading has on the corneal wound healing response after PRK.     

Confocal microscopy changes in epithelial and stromal thickness up to 7 years after LASIK and photorefractive keratectomy for myopia

PURPOSE: To determine the long-term changes in epithelial, stromal, and corneal thickness after LASIK and photorefractive keratectomy (PRK). METHODS: In two prospective observational case series, 11 patients (16 eyes) received LASIK and 12 patients (18 eyes) received PRK to correct myopia or myopic astigmatism. None of the corneas had retreatment procedures. Corneas were examined using confocal microscopy before and at 1 month, and at 1, 2, 3, 5, and 7 years after surgery. Central thicknesses were measured from reflected light intensity profiles recorded by confocal microscopy. Postoperative epithelial thickness was compared to preoperative, and postoperative stromal and corneal thicknesses were compared to thickness at 1 month after surgery. RESULTS: In LASIK, epithelial thickness at 1 month (51 +/- 4 microm, n = 11) was greater than before surgery (41 +/- 4 microm, n = 16; P < .001) and remained thicker through 7 years (52 +/- 6 microm, n = 13; P < .001). Stromal and corneal thickness did not change between 1 month and 7 years after LASIK. After PRK, corneal thickness at 1 year (464 +/- 44 microm, n = 17) was greater than at 1 month (442 +/- 39 microm, n = 15; P = .001) and remained thicker at 7 years after PRK (471 +/- 45 microm, n = 17; P > .001). CONCLUSIONS: The early increase in central epithelial thickness after myopic LASIK persists for at least 7 years and is probably the result of epithelial hyperplasia. Central corneal thickness increases during the first year after PRK and remains stable thereafter up to 7 years.     

LASEK与PRK术后角膜组织结构的活体激光共聚焦显微镜观察

目的 评价活体共聚焦显微镜(confocal microscopy through focusing，CMTF）在观察准分子激光上皮下角膜磨镶术(LASEK)与准分子激光角膜切削术(PRK)后创面修复过程中的作用。方法 对高度近视患者31人(62只眼)角膜进行CMTF检查。结果 通过连续共聚焦扫描及焦点分析，得到角膜精确的、可重复的、深径度的图像，X、Y轴和Z轴多层情况及实时四维显示。LASEK术后角膜上皮细胞及基底细胞的形态及紊乱程度的变化、术后相同时相点产生的瘢痕均弱于PRK术后同时期。结论 应用共聚焦显微镜可直接观测活体角膜各层细胞形态结构，为准分子激光屈光性角膜手术后创面修复、手术效果的评价提供有利证据。     

Corneal response to femtosecond laser photodisruption in the rabbit

In this report we evaluated the effect of femtosecond laser energy on the development of corneal haze and keratocyte activation in rabbits following intra-stromal photodisruption to create LASIK flaps using a modified commercial femtosecond surgical laser. Three groups of flap parameters were studied: 1.5 microJ/pulse with 10 microm spot separation and complete side cut (Group 1); 3.5 microJ/pulse with 14 microm spot separation and complete side cut (Group 2); 3.5 microJ/pulse with 14 microm spot separation and partial (50 microm) side cut (Group 3). All flaps were left attached without lifting to avoid epithelial contamination. Rabbits were then evaluated pre- and post-operatively by quantitative in vivo and ex vivo confocal microscopy. The achieved flap thickness 1 week after surgery averaged 88.9+/-12.8, 90.8+/-6.9 and 86.5+/-6.8 microm for Groups 1-3 respectively (p=NS). Interface thickness was significantly greater (p<0.05) in the higher energy groups averaging 40.0+/-11.2 and 37.7+/-5.7 microm for Groups 2-3 compared to 28.6+/-4.5 microm for Group 1. Corneal haze was barely detectible and not significantly different between groups, although haze was detected in the region of the side-cuts in Groups 1 and 2. No clinically significant changes in stromal or epithelial thickness were noted. Laser confocal microscopy showed the presence of small diameter cells within the flap interface that resided within disrupted regions of the corneal collagen lamellae. Keratocyte activation was only detected in regions of the 100% side cut and not over the flap interface. In conclusion, the results of this study indicate that photodisruption of the corneal stroma alone without flap elevation regardless of laser energy does not induce significant corneal haze in the rabbit. However, a thicker stromal interface was seen with the higher energy suggesting greater stromal damage.     

A new paradigm for corneal wound healing research: the white leghorn chicken (Gallus gallus domesticus)

PURPOSE: To evaluate the chicken cornea as a model for corneal wound healing research. METHODS: We conducted studies on normal chicken corneas and on corneas following mechanical debridement and photorefractive keratectomy (PRK). RESULTS: The chicken cornea possesses six distinct layers that resemble the layers of the human cornea, including a substantial Bowman's layer measuring 5.2 +/- 0.3 microm thick. Reepithelialization time was 44.8 +/- 1.1 hours with a sliding rate of 75.3 +/- 3.2 microm/hour following mechanical debridement and 54.4 +/- 2.8 hours with a sliding rate of 63.3 +/- 3.2 microm/hour for PRK-treated corneas. Biomicroscopic haze post-PRK peaked at 4-6 weeks and regressed until 20 weeks post-PRK. Histologic and clinical observations of wound healing strongly paralleled that noted in humans. CONCLUSION: The chicken cornea's morphology and wound healing response render it a useful model for corneal wound healing investigations.     

LASIK vs LASEK vs PRK: advantages and indications

The advent of the excimer laser as an instrument for use in reshaping the corneal stroma was a great step forward in refractive surgery. Laser energy can be delivered on the stromal surface in the photorefractive keratectomy (PRK) procedure or deeper on the corneal stroma by the means of a lamellar surgery in which a flap is created with the microkeratome in the laser in situ keratomileusis (LASIK) procedure. LASIK is currently the dominant procedure in refractive surgery. The main advantage of LASIK over PRK is related to maintaining the central corneal epithelium. This increases comfort during the early post-operative period, allows for rapid visual recovery, and reduces the wound healing response. Reduced wound healing correlates with less regression for high corrections and a lower rate of complications such as significant stromal opacity (haze). PRK, however, remains as an excellent option for mild to moderate corrections, particularly for cases associated with thin corneas, recurrent erosions, or a predisposition for trauma (Martial arts, military, etc.). Recently, a modification of PRK, laser subepithelial keratomileusis (LASEK), was introduced. In the LASEK procedure, an epithelial flap is created and replaced after the ablation. The benefits, if any, of the creation of an epithelial flap compared to traditional PRK are not fully appreciated. Advocates of LASEK suggest that there is less discomfort in the early postoperative period, faster visual recovery, and less haze compared to standard PRK for correction of similar levels of refractive error. Additional long-term clinical studies, along with laboratory research, will be crucial to validate these potential advantages of LASEK procedure.     

Validation of confocal microscopy through focusing for corneal sublayer pachymetry

PURPOSE: To evaluate the accuracy and precision of confocal microscopy through focusing (CMTF) for corneal sublayer pachymetry. METHODS: A tandem scanning confocal microscope equipped with a nonapplanating contact objective was used to perform CMTF. The accuracy of CMTF measurements was evaluated using nine custom-made calibration contact lenses (PMMA) with varying thickness (300-600 microm) and radius of curvature (7.0-9.0 mm). The influence of immersion fluid stabilization and the consequence of prolonged corneal examination were assessed by performing CMTF in rabbits. Additionally, factors related to the instrumental setup and to sedation of experimental animals were examined. RESULTS: For all calibration contact lenses, the thickness measured by CMTF was within +/-1.0 microm of the certified value. Varying the target thickness or radius of curvature had no consistent impact on the high accuracy of CMTF. When performing CMTF in vivo, z-axis motion was readily identified by sampling and comparing both in- and out-scans. Apart from involuntary eye movements, z-axis motion was due to initial thinning of the immersion fluid with stabilization obtained after approximately 1.5 minutes. Continued confocal examination led to slight but significant swelling of both the stroma (0.5 microm/min) and epithelium (0.1 microm/min). CONCLUSIONS: CMTF is an accurate and precise technique for corneal sublayer pachymetry with concurrent display of cellular morphology. The precision of CMTF can be improved by allowing time for methylcellulose stabilization and by performing repeated two-way (in and out) scans to account for z-axis motion.     

Scraping and mitomycin C to treat haze and regression after photorefractive keratectomy for myopia

PURPOSE: To evaluate the efficacy, safety, and predictability of therapeutic scraping and application of a diluted 0.02% mitomycin C solution to treat haze and regression after photorefractive keratectomy (PRK) for myopia. METHODS: We performed a non-comparative, non-randomized retrospective study of 35 eyes of 30 patients who had previously undergone PRK for myopia and developed haze and regression after treatment. The range of refractive error after regression was -0.75 to -5.50 D (mean -2.92 D). Haze, ranging from grade 3 to 4 (scale: 0 to 4) caused a best spectacle-corrected visual acuity loss of 1 to 6 Snellen lines. All eyes were treated 6 to 12 months after PRK by scraping the stromal surface and application of a 0.02% mitomycin C solution for 2 minutes using a soaked merocel sponge. No laser ablation was performed. Corneal transparency, refractive error, and visual outcomes were evaluated over a 12-month follow-up period. RESULTS: All eyes had significant improvement in corneal transparency. Thirty-one eyes had haze grades lower than 1, which were maintained over time. Only four eyes showed haze grades 1 to 2 and two of them needed further treatment using the same technique. At 12 months after treatment, all eyes were within +/-1.50 of original intended correction (mean 0.04 +/- 0.63 D). BSCVA improved in all eyes. No toxic effects were observed during re-epithelialization or during follow-up. CONCLUSION: Single application of diluted mitomycin C 0.02% solution following scraping of the corneal surface was effective and safe in treating haze and regression after PRK.     

兔LASEK与PRK术后角膜Ⅰ、Ⅲ、Ⅴ、Ⅵ型胶原的Western Blot研究

目的:用WesternBlot法比较准分子激光上皮下角膜磨削术(LASEK)与准分子激光角膜切削术(PRK)术后角膜Ⅰ、Ⅲ、Ⅴ、Ⅵ型胶原的动态变化情况。方法:52只新西兰白兔分为8组,对每只兔右眼行LASEK,左眼行PRK。术后1d、7d、1个月、3个月、4个月、5个月、6个月观察Haze情况,处死动物取角膜行Ⅰ、Ⅲ、Ⅴ、Ⅵ型胶原的动态变化过程的免疫组织化学检查与WesternBlot检测。结果:经免疫组化和WesternBlot研究发现:LASEK组术后角膜基质中Ⅰ、Ⅲ型胶原开始增生的时间早于PRK组,表达的强度与PRK组有显著差异;两组的Ⅴ、Ⅵ型胶原动态变化曲线相似,达到表达高峰的时间一致,PRK组Ⅴ、Ⅵ型胶原的表达均明显高于LASEK组,术后6个月时LASEK组表达显著弱于PRK组。结论:PRK手术后角膜基质中Ⅰ、Ⅲ、Ⅴ、Ⅵ型胶原的表达强度、达到高峰及恢复正常的时间与LASEK相比存在显著差异,表明PRK术后基质内有胶原的过量沉积,可能是临床PRK术后Haze严重及屈光回退的组织学基础。WesternBlot法是一种可比较准确地半定量检测胶原含量动态变化的研究方法。     

Intact corneal epithelium is essential for the prevention of stromal haze after laser assisted in situ keratomileusis

AIMS: To determine the effect of intact corneal epithelium on stromal haze and myofibroblast cell formation after excimer laser surgery. METHODS: Denuded epithelium alone, photorefractive keratectomy (PRK), laser in situ keratomileusis (LASIK), or LASIK with denuded epithelium was performed in rabbit eyes. Postoperative anterior stromal haze was assessed employing a standard scale. Immunohistochemical methods were used to detect alpha smooth muscle actin (alpha-SMA), a marker for myofibroblastic cells, and type III collagen in subepithelial corneal tissue. RESULTS: Three weeks after surgery, the presence of alpha-SMA positive long extended and spindle-shaped stromal cells, and synthesis of type III collagen were observed in the subepithelial stromal layer corresponding to corneal haze in PRK and LASIK with denuded epithelium, but not in denuded epithelium alone and LASIK. CONCLUSION: The intact corneal epithelium may play an important part curbing subepithelial haze and differentiation of myofibroblasts in corneal wound healing.     

Long-term outcomes of photorefractive keratectomy in eyes with previous epikeratophakia for keratoconus

PURPOSE: To determine the long-term safety and effectiveness of photorefractive keratectomy (PRK) in the treatment of refractive errors after epikeratophakia (EP) for keratoconus. METHODS: Ten patients (14 eyes) who had refractive errors after EP for keratoconus received PRK surgery. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refractive error, corneal astigmatism, pachymetry, corneal topography, and complications were monitored. RESULTS: Mean follow-up after PRK was 63.4 +/- 19.8 months. Mean spherical equivalent was -5.5 +/- 3.9 D before PRK, -0.9 +/- 0.5 D at 1 month after PRK, and -1.5 +/- 1.0 D at 3 years. Mean astigmatism was 4.2 +/- 2.1 D before PRK, 1.2 +/- 0.5 D at 1 month after PRK, and 1.5 +/- 0.6 D at 3 years. Thirteen (93%) eyes had an UCVA <20/40, and 12 (86%) had a BSCVA of 20/40 or better before PRK. At 1 year, the UCVA was 20/40 or better in 8 (57%) eyes, and the BSCVA was 20/40 or better in all eyes. Mean central corneal thickness was 749 +/- 35 microm before PRK and 621 +/- 56 mum at 3 years. During the follow-up period, haze (grade no more than 1.0) was observed in 2 eyes. No immune rejection episode or recurrent keratoconus was found. CONCLUSIONS: PRK appears to be reliable and safe for the correction of residual ametropia after EP for keratoconus, and the visual acuity can remain stable after PRK for a long time.     

Effectiveness of cultured human keratinocyte onlays on epithelial healing and clinical outcome after photorefractive keratectomy

PURPOSE: To evaluate epithelial healing time, postoperative pain, corneal haze, and visual and refractive outcomes following the application of cultured sheets of human allogeneic epidermal keratinocyte (CEAK) onlays on the photorefractive keratectomy (PRK) -ablated corneal surface as dressing material. METHODS: In total, 204 eyes from 103 patients with myopia or myopic astigmatism were prospectively evaluated for 6 months after PRK. The ablated cornea was dressed in three different ways. Specifically, CEAK onlays were placed in 80 eyes (CEAK group), CEAK with amniotic membrane (AM) strips in 63 eyes (CEAK with AM group), and therapeutic contact lenses only in 61 eyes (control group). All eyes were covered with bandage contact lens after the operation. Contact lens removal time, intensity of postoperative pain score on postoperative day 2, corneal haze, Snellen visual acuity, and remaining refractive errors were measured. RESULTS: The mean contact lens removal time was shorter in the CEAK with AM group (1.84 +/- 0.72 days) compared to the control (2.77 +/- 1.59 days) and CEAK only (2.24 +/- 0.79 days) groups (P < .001). However, no significant differences were evident among the groups in terms of immediate postoperative pain, Snellen visual acuity, remaining refractive errors, and corneal haze at 6 months postoperative. CONCLUSIONS: The CEAK onlay with AM facilitates epithelial healing, and is thus a good candidate dressing material to decrease the epithelial healing time after PRK. However, this onlay method did not affect the intensity of postoperative pain or final visual outcomes after surgery.