Effect of cytochrome c peroxidase on corneal epithelial healing process after photorefractive keratectomy

PURPOSE: To evaluate the role of commercially prepared cytochrome c peroxidase eyedrops in corneal epithelial healing after photorefractive keratectomy (PRK). SETTING: Department of Pathophysiological Optics, Faculty of Medicine, University of Bologna, Bologna, Italy. METHODS: Seventy-two eyes of 36 patients affected by low to moderate refractive error (myopia and myopic astigmatism) had uneventful bilateral photorefractive keratectomy (PRK). In each patient, 1 eye (32 eyes) received standard postoperative therapy plus cytochrome c peroxidase eyedrops (3 times a day for 1 week or until corneal reepithelialization was completed, corresponding to 15 000). The fellow eye served as the control and received standard postoperative therapy plus placebo. Patients were monitored daily starting the day after surgery for 7 days to evaluate the corneal reepithelialization rate using a video slitlamp camera with a cobalt blue light. Mean diameter of corneal wounds was measured. Videotaped images were recorded and analyzed by computer planimetry. RESULTS: All the eyes treated with cytochrome c peroxidase eyedrops healed completely before day 5 postsurgery, with a mean reepithelialization time of 91 hours +/- 14 (SD); the mean reepithelialization time was 154 +/- 9 in eyes receiving placebo (P<.05); the mean reepithelialization rate was 0.066 +/- 0.007 mm/hour in the cytochrome c peroxidase group and 0.039 +/- 0.006 mm/hour in the control group (P<.05). There were no statistically significant differences between groups in corneal haze presentation during follow-up (P =.70), perhaps because the time period was too brief (7 days). However, corneal clarity, on slitlamp biomicroscopy in the study group was greater than in the control group. No side effects or toxic effects were documented. CONCLUSIONS: These data suggest that cytochrome c peroxidase significantly accelerates epithelial healing after PRK. Further clinical study should be performed to prove the results obtained in this pilot study and the long-term efficacy of cytochrome c peroxidase to prevent corneal haze.     

角质细胞生长因子促进角膜上皮损伤修复的研究

目的寻找促进角膜上皮损伤修复，治疗持续性角膜上皮缺损的有效方法。方法用３Ｈ－胸腺嘧啶核苷（３Ｈ－ＴｄＲ）掺入及液体闪烁技术，观察不同浓度的外源性角质细胞生长因子（ｋｅｒａｔｉｎｏｃｙｔｅｇｒｏｗｔｈｆａｃｔｏｒ，ＫＧＦ）对体外培养的人角膜上皮细胞生长的影响，由此推算出有效滴眼液浓度并应用于兔眼。用计算机图形分析系统计算角膜上皮愈合速率；用光镜和电镜评估愈合的质量。结果０．１～１００ｎｇ／ｍｌＫＧＦ有明显促进体外培养的人角膜上皮细胞生长的作用（增长率为２７．６６％～７６．７３％），且呈剂量依赖性（ｒ＝０．９２３３，Ｐ＜０．００１）。１μｇ／ｍｌＫＧＦ滴兔眼，加速了角膜上皮损伤修复（愈合速率，ＫＧＦ组为１．７７±０．２３ｍｍ２／ｈ，与对照组１．４９±０．２４ｍｍ２／ｈ比较，Ｐ＜０．０５）。结论外源性ＫＧＦ对体外培养的人角膜上皮细胞有明显的促生长作用，其滴眼液有加速兔眼角膜上皮创伤修复的作用。     

准分子激光屈光性角膜切削术后角膜上皮愈合的影响因素

目的　探讨年龄、性别、绷带式隐形眼镜配戴、术后局部使用不同药物及手术切削深度诸因素对PRK术后角膜上皮愈合的影响。方法　对 2 5 8例实施PRK术病人 (393只眼 )进行前瞻、随机、双盲、设立安慰剂对照的临床研究。结果　不同年龄、性别、术后配戴隐形眼镜及手术切削深度诸因素对角膜上皮愈合时间无显著性差别 (P >0 0 5 )。术后使用双氯灭痛滴眼液、透明质酸钠及安慰剂组角膜上皮愈合的时间分别是 :3 78天± 1 37天、2 86天± 1 44天、3 31天± 1 5 0天 (P <0 0 5 )。结论　年龄、性别、术后配戴隐形眼镜以及手术切削深度对PRK术后角膜上皮愈合不构成影响 ,而双氯灭痛可延长角膜上皮愈合 ,透明质酸钠可促进角膜上皮的修复。     

Effect of the combination of basic fibroblast growth factor and cysteine on corneal epithelial healing after photorefractive keratectomy in patients affected by myopia

Background:

This study sought to evaluate the effect of basic fibroblast growth factor eye drops and cysteine oral supplements on corneal healing in patients treated with photorefractive keratectomy (PRK).

Materials and Methods:

One hundred and twenty patients treated bilaterally with PRK for myopia were enrolled at one of two eye centers (Clinica Santa Lucia, Bologna, Italy and Department of Ophthalmology, University of Magna Graecia, Catanzaro, Italy) and were treated at the former center. Sixty patients included in the study group (Group 1) were treated postoperatively with topical basic fibroblast growth factor plus oral L-cysteine supplements, whereas 60 subjects included in the control group (Group 2) received basic fibroblast growth factor eye drops. We recorded the rate of corneal re-epithelialization and patients were followed-up every 30 days for 6 months. Statistical analyses were performed on the collected data.

Results:

The eyes in Group 1 demonstrated complete re-epithelialization at Day 5, whereas the eyes in Group 2 achieved this status on Day 6. No side-effects were reported.

Conclusions:

Patients treated with basic fibroblast growth factor eye drops and L-cysteine oral supplements benefit from more rapid corneal re-epithelialization. In human eyes, this combination treatment appeared to be safe and effective in accelerating corneal surfacing after surgery.

Financial Disclosure:

No author has any financial or proprietary interest in any material or method used in this study.

Trial Registration:

Current Controlled Trials ISRCTN73824458.     

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.     

自体血清滴眼液对屈光性角膜切削术后角膜上皮愈合的影响

目的：研究自体血清滴眼液对屈光性角膜切削术(PRK)后角膜上皮愈合的影响。

方法：本研究共纳入20例40眼近视及近视散光患者,其中男性9例,女性11例。每例患者随机选取一眼作为研究组应用20%含自体血清的人工泪液,另一眼为对照组应用常规人工泪液。PRK 术中,40眼均于角膜表面居中放置直径8 mm的酒精储槽, 20%的酒精作用20s。术后每天观察直到角膜上皮愈合后,分别于1mo,6mo,12mo进行随访。上皮愈合时间为主要观察指标,并记录裸眼视力(UCVA),显然验光和混浊度。

结果：两组间术前小瞳检影结果无明显差异。术后1d,2d,3d,研究组平均疼痛评分均显著低于对照组(P<0.05)。术后1d,3d,研究组的平均水平和垂直上皮缺损低于对照组(P<0.05)。研究组上皮完全愈合的平均时间比对照组短约0.7d(3.15±0.366d vs 3.85±0.587d, P=0.00)。

结论：研究表明,应用自体血清滴眼液,通过加速角膜上皮愈合和减轻疼痛,从而缩短视力恢复时间,降低屈光性角膜切削术术后不适、混浊度和感染风险。     

Effect of beam variables on corneal sensitivity after excimer laser photorefractive keratectomy

AIM—To investigate changes in corneal touch sensitivity following excimer laser photorefractive keratectomy (PRK) using different beam configurations.
METHODS—20 subjects were given a unilateral −3.00 D correction with either a 5 mm (26 µm, n=10) or 6 mm (42 µm, n=10) beam diameter. Thirty subjects underwent a unilateral −6.00 D correction with 5 mm (62 µm, n=10), 6 mm (78 µm, n=10), or multizone (62 µm, n=10) treatments. The multizone treatment was 6 mm in diameter with the depth of the 5 mm treatment. Corneal sensitivity was measured using a slit-lamp mounted Cochet-Bonnet aesthesiometer before and at 1, 3, 6, and 12 months after PRK. Stimulus locations included points lying within the ablated zone (central) and outside (peripheral). These were compared with the equivalent locations in control (untreated) eyes.
RESULTS—There was a significant reduction in corneal sensitivity within the central (ablated) zone in all treatment groups after PRK. In most groups a return to full sensitivity was achieved by 6 months with the exception of the multizone treatment group which showed significant corneal hypoaesthesia at 12 months. Peripheral corneal sensitivity was also reduced in this group up to 3 months after the procedure. A comparison between the −3.00 D and −6.00 D treatment groups showed no significant difference. However, combining data from all treatment groups, a significant correlation was found between the interocular difference in central corneal sensitivity and postoperative haze at 3 and 6 months.
CONCLUSIONS—For corrections up to −6.00 D ablation depth and treatment zone diameter do not appear to be clinically important determinants of corneal hypoaesthesia. In contrast, postoperative corneal haze appears to correlate with sensitivity loss.

     

Intraoperative mitomycin and corneal endothelium after photorefractive keratectomy

PURPOSE: To determine whether there is an increased risk to the corneal endothelium when mitomycin C (MMC) is administered after photorefractive keratectomy (PRK). DESIGN: Prospective, randomized, double-blind, placebo-controlled crossover trial. METHODS: Corneal endothelium was analyzed preoperatively and postoperatively in 18 eyes of nine patients who were administered either MMC- or balanced salt solution (BSS)-supplemented PRK at Codet Aris Vision, Tijuana, Mexico. After laser ablation, one eye was randomly assigned to intraoperative topical MMC 0.02% treatment for 30 seconds, and the fellow eye (the control eye) was treated in a standard fashion with topical BSS. Preoperative pachymetry and endothelial cell count were performed and compared with postoperative measurements after one month and three months. Main outcome measure studied was endothelial cell loss. RESULTS: There was no significant difference in the preoperative endothelial cell count between the 2 groups: MMC group 2835 +/- 395, control group 2779 +/- 492, P = .62. In the control group, at one month and three months the difference in the endothelial cell count was not statistically significant (P = .27, P = .14, respectively). However, in the MMC group the endothelial cell loss was statistically significant: at one month 14.7 +/- 5.1%, and at three months 18.2 +/- 9.0% (P = .0006, P = .002, respectively). CONCLUSIONS: The use of intraoperative topical MMC 0.02% for 30 seconds after PRK may affect the endothelial cell count.     

准分子激光屈光性角膜切削术后角膜地形图的变化

目的探讨准分子激光屈光性角膜切削术（ＰＲＫ）后角膜表面形态和屈光力变化。方法ＴｏｍｅｙＴＭＳ２ＴＭ角膜地形图检查１２４只近视眼ＰＲＫ术前、术后１、６月和１年统计值的变化。结果ＰＲＫ术后眼绝对等级角膜地形图见梯度明显的蓝色低屈光带。ＳＲＩ和ＳＡＩ术后１月时比术前和术后６月、１年时高，ＩＡＩ术前后无变化。近视眼治疗等值球镜屈光度分别与ＳＲＩ、ＳＡＩ和ＩＡＩ的相关系数为０．７６６、０．４６１和－０．１０５。结论ＰＲＫ术后角膜屈光力稳定性较好，对角膜表面规则性和对称性早期有影响，逐渐恢复正常。ＰＲＫ角膜切削区带越多，对角膜表面形态影响越大。     

Bilateral corneal infiltrates after excimer laser photorefractive keratectomy

A 26-year-old man developed painless inferior subepithelial infiltrates away from the site of ablation in both eyes after excimer laser photorefractive keratectomy (PRK) for myopia. Clinical characteristics of the corneal infiltrates resembled staphylococcal-immune infiltrates. The condition responded to treatment with topical diluted steroids and antibiotics. There was no residual corneal scarring. The infiltrates did not affect the refractive outcome of the surgery. Recognition of this rare entity will help clinicians avoid aggressive investigative and treatment modalities that can affect the results of PRK.     

Changes in posterior corneal curvature after photorefractive keratectomy

PURPOSE: To determine whether myopic ablation by excimer laser photorefractive keratectomy (PRK) affects only the anterior curvature of the cornea or whether changes also occur in the posterior corneal curvature. SETTING: Department of Optometry and Neuroscience, UMIST, and Optimax Laser Eye Clinic, Manchester, United Kingdom. METHODS: Sixteen patients who presented for correction of myopia in 1 eye by excimer laser PRK were followed for 3 months. Only newly presenting patients were recruited, and the untreated eyes were used as controls. The patients were examined at the initial visit (0 week) and 6 and 12 weeks post-PRK. Measurements included Orbscan topography and pachymetry, autokeratometry, and ultrasound pachymetry. RESULTS: The mean patient age of the 8 men and 8 women was 29.6 years +/- 8.6 (SD) (range 20 to 47 years). The attempted mean spherical equivalent correction was between -1.73 and -6.43 diopters. Anterior corneal curvature and corneal thickness in the treated eyes changed systematically in relation to the amount of ablation. Posterior corneal curvature steepened in relation to the dioptric power treated. There were systematic differences between the pachymetry values obtained with the Orbscan and the ultrasound pachymeter. CONCLUSIONS: The results suggest that after myopic PRK, the thinner, ablated cornea may bulge forward slightly to steepen both anterior and posterior curvatures. This may account for the regression toward myopia that is typically found in the first few days posttreatment. The forward bulging is similar to the corneal relaxation effects observed after radial keratotomy.     

Ascorbate prophylaxis for corneal haze after photorefractive keratectomy

PURPOSE: To evaluate whether prophylactic systemic ascorbic acid influences the average level of haze and the incidence of late onset corneal haze after photorefractive keratectomy (PRK). METHODS: Two consecutive groups of eyes treated with PRK for myopia with or without astigmatism were retrospectively compared. The patients had been treated similarly, with the exception that systemic ascorbate had been supplied orally in one of the groups. Haze intensity was quantified on a scale from 0 (clear cornea) to 4 (anterior chamber not visible). The diagnostic criterion for late onset corneal haze was a haze grade 2 or higher, occurring 4 to 12 months after surgery. RESULTS: One week, 1, 3, 6, and 12 months after surgery, the group without ascorbate (314 eyes) showed haze of average levels 0.61, 0.51, 0.50, 0.32, 0.10, respectively, and the group with ascorbate (201 eyes) showed haze of average levels 0.38, 0.18, 0.16, 0.09, 0.06, respectively. Comparison of the respective values showed a statistically significant difference between the two groups (P<.01) at 1 week, 1, 3, and 6 months. Late onset corneal haze was observed in 11 eyes in the group without ascorbate, and none was observed in the group with ascorbate (P<.02). CONCLUSION: This retrospective nonrandomized clinical study suggests that oral ascorbic acid supplementation may have a prophylactic effect against haze development after PRK. However, routine prophylactic use of ascorbate can be recommended only after a randomized, prospective clinical trial substantiates its efficacy.     

羊水对准分子激光角膜切削术后组织功能恢复的影响

目的 探讨局部应用羊水（human amniotic fluid,HAF）对准分子激光角膜切削术（photorefractive keratectomy,PRK）后角膜知觉及透明度恢复的影响。方法 新西兰白兔36只,双眼行PRK。术后,右眼为实验眼滴用HAF液,左眼作为对照眼滴用人工泪液（artificial tears,AT）。术后不同时期分别进行裂隙灯、Cochet-Bonnet角膜知觉计及722光栅分光光度计检查,并进行两组比较。结果 术后第3～第5天两组角膜上皮全部愈合,差异无显著性（P〉0.05）。术后第1周、第4周、第8周、第12周及第16周（第2周除外）,实验组角膜知觉敏感度、透明度均高于对照组（P〈0.05）;术后第4周、第8周、第12周及第16周,实验组角膜透明度均高于对照组（P〈0.05）。结论 HAF滴眼液能促进PRK后角膜知觉及透明度的恢复,该研究将为浅表角膜损伤提供新的治疗途径。     

Effects of topical tranilast on corneal haze after photorefractive keratectomy

PURPOSE: To determine whether topical tranilast might reduce corneal haze through suppression of transforming growth factor (TGF)-beta1 synthesis in keratocyte after photorefractive keratectomy. SETTING: Department of Ophthalmology, Korea University College of Medicine, Seoul, Republic of Korea. METHODS: Photorefractive keratectomy was performed on 48 eyes of 28 white rabbits and 24 eyes in a tranilast group were treated with tranilast solution, and the other 24 eyes in control group were treated with saline after laser ablation. The grades of corneal haze at 1, 2, 4, and 8 weeks after surgery were evaluated in 10 eyes of each group for comparison. Immunohistochemistry was performed on 10 eyes of each group, and Western blot analysis was done on 4 eyes of each group for studying TGF-beta1 expression at postoperative day 7. RESULTS: There was no statistically significant difference in corneal haze between 2 groups from week 1 to week 4 after surgery, but a significant difference was found at week 8 after photorefractive keratectomy (P=.02). The mean number of keratocytes that expressed TGF-beta1 in the tranilast group was 58.3 (+/-17.2), which showed significant difference, compared with that of the control group, 104.5 (+/-23.0) (P<.01). Western blot analysis also revealed that the amount of TGF-beta1 in tranilast group was slightly less than the control group. CONCLUSIONS: Topical tranilast could reduce corneal haze by suppressing TGF-beta1 expression in keratocytes after photorefractive keratectomy.     

Visual outcomes of sterile corneal infiltrates after photorefractive keratectomy

Purpose:Sterile infiltrates following laser refractive surgery is an uncommon complication. This study was undertaken to analyze the visual outcomes of sterile infiltrates following photorefractive keratectomy (PRK).Methods:This retrospective study included 14 eyes that developed sterile infiltrates following PRK out of a total of 6280 eyes that underwent PRK between 2014 and 2017. Medical records of these patients, including patient demographics, characteristics of the infiltrate, presenting visual acuity, and treatment outcomes were recorded and analyzed.Results:The incidence of sterile corneal infiltrates post-PRK in our study was 0.22% (14/6280). The mean age of the patients was 27.42 ± 4.87 years. The uncorrected visual acuity (UCVA) at presentation was 0.49 ± 0.13 log MAR units. The mean size of the infiltrate was 3.22 ± 2.85 mm². All cases were successfully managed medically with topical steroids. The mean UCVA and best-corrected visual acuity (BCVA) at the last follow-up visit were 0.08 ± 0.08 and 0.05 ± 0.07 log MAR units, respectively. The mean time taken for resolution of the infiltrate was 8.91 ± 4.57 days.Conclusion:Sterile infiltrates following PRK can be effectively treated with aggressive topical steroids. The outcome is generally favorable and does not require surgical intervention if treatment is instituted early.     

准分子激光角膜切削术后角膜地形图的分析

目的：准分子激光角膜切削术（ＰＲＫ）后角膜性状和视力质量和研究。方法：对２３例（３８只眼）近视患者于术后１、３、６个月进行角膜地形图随访。结果：ＰＲＫ术后角膜表面的球面性状发生一定改变。随着时间推移，角膜表面规则指数（ＳＲＩ）和表面不规则指数（ＳＡＩ）均逐渐降低，角膜变得中平滑。模拟角计数数表现一定的回退。术后６个月时，角膜地形图主要表现为四种形态；圆形或椭圆形、哑铃形、半环形、中央小岛形、有珞种