Epithelial healing and ocular discomfort after photorefractive keratectomy in children

OBJECTIVE: To document the rate of healing of the corneal epithelial defect created by photorefractive keratectomy (PRK) and the degree of discomfort experienced by children treated with PRK. SETTING: Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA. METHODS: Ten patients between 3 and 10 years of age were treated with PRK for severe anisometropia. All had anisometropic amblyopia refractory to conventional therapy with glasses or contact lenses and occlusion therapy. The size of the corneal epithelial defect was documented daily until the defect healed completely. Postoperative discomfort was documented daily using a pain-assessment scale until the epithelial defect healed completely. RESULTS: Two children were treated with PRK for hyperopic anisometropia; the rest were treated for myopic anisometropia. Cumulatively, the corneal epithelium had healed completely by day 3 in 6 patients (60%), by day 4 in 9 patients (90%), and by day 5 in all patients. The mean healing time was 3.5 days. Patients experienced mild discomfort on the day of surgery and on the first postoperative day. They had minimal pain on day 2. After day 2, no patient reported pain or other discomfort. CONCLUSIONS: The corneal epithelial defect created by PRK healed promptly and was associated with minimal postoperative discomfort in children treated with the protocol described.     

Wound healing after photorefractive keratectomy

For more than 15 years, the excimer laser has been used as a surgical instrument on the cornea. Photorefractive keratectomy (PRK) followed radial keratotomy as researchers sought a more precise technique. In PRK, precision turned out to depend on surgical technique as well as the wound-healing process, with the 2 factors interdependent. The PRK technique has evolved toward a large diameter, flat ablation curvatures, and an even surface. The role of such factors as cytokines and interleukins has become more clear in the past 10 years. However, understanding the wound-healing process becomes more complicated with increasing know edge. Learning the contributing factors and performing trials with new drugs and antibodies to modulate wound healing have shown positive results on the experimental level. Patient selection based on the concentration of epidermal growth factor in tears may be another way to increase PRK s precision. The PRK technique has taught much about wound healing. For the technique to be competitive, increased precision, particularly in eyes with high myopia, is needed. Two other factors are imperative: controlling postoperative pain and decreasing visual rehabilitation time.     

Ascorbic acid levels in human tears after photorefractive keratectomy, transepithelial photorefractive keratectomy, and laser in situ keratomileusis

PURPOSE: To investigate the level of ascorbic acid in human tear fluid after photorefractive keratectomy (PRK), transepithelial PRK, and laser in situ keratomileusis (LASIK). SETTING: Departments of Ophthalmology and Biochemistry, School of Medicine, Gazi University, Ankara, Turkey. METHODS: Twenty patients (7 women and 13 men) were included in this study. Traditional PRK with epithelial scraping by a blunt spatula followed by surface ablation (7 eyes), transepithelial PRK (7 eyes), or LASIK (6 eyes) was performed. Tears were collected preoperatively and 1 and 5 days postoperatively. Ascorbic acid levels were measured using 2-4 dinitrophenylhydrazine. RESULTS: Ascorbic acid levels in the tear fluid were decreased significantly 1 day after PRK, transepithelial PRK, and LASIK (P <.05). On the fifth day, the ascorbic acid levels were significantly lower than preoperatively in all groups. CONCLUSION: After PRK, transepithelial PRK, and LASIK, the ascorbic acid levels of the tear fluid decreased significantly. Because ascorbic acid is the major scavenger of superoxide radicals in tears, topical ascorbic acid therapy may help eliminate the harmful effect of free radicals from excimer laser surgery.     

Plasminogen activator activity in tears after excimer laser photorefractive keratectomy

PURPOSE: To quantify changes of plasminogen activator activity in tear fluid during corneal re-epithelialization after excimer laser photorefractive keratectomy (PRK). METHODS: Tear samples were collected with glass capillaries from 77 eyes of 42 patients immediately before and immediately after PRK treatment and on postoperative days 3 and 5. In 20 patients, the contralateral eye was similarly sampled to serve as control. Plasminogen activator activity in the tear samples was measured by a spectrophotometric method using human plasminogen and chromogenic peptide substrate, D-valyl-L-leucyl-L-lysine-p-nitroanilide (S-2251). RESULTS: In tears of all eyes that underwent PRK, the plasminogen activator activities were lower immediately after PRK than were the preoperative values. For patient eyes with normal wound healing, tear plasminogen activator activities were significantly elevated above the preoperative level on the third postoperative day and then returned to the preoperative level by the fifth postoperative day. In contrast, tear plasminogen activator activities remained low through the third postoperative day in all (six) eyes in which haze developed after 3 to 6 months. The contralateral control eyes showed no appreciable change in plasminogen activator activity over the 5-day period. CONCLUSIONS: Plasminogen activator activity levels measured in tears of excimer laser PRK-treated eyes may serve as a predictor of wound healing. Extended low levels of plasminogen activator activity through the third postoperative day correlate with the development of corneal healing abnormalities (haze). The low plasminogen activator activity could be not only an accompanying sign but also a cause of defective corneal wound healing.     

Plasminogen activator activity and inhibition in rabbit tears after photorefractive keratectomy

Plasminogen activator is a normal component of tear fluid that plays a role in corneal wound healing processes. This work examines whether inhibitor-induced low levels of plasminogen activator activity (PAA) during corneal re-epithelialization after excimer laser photorefractive keratectomy (PRK) correlates with the eventual occurrence of haze in rabbit eyes. Tear samples were collected with glass capillaries from 16 eyes of eight New Zealand rabbits, using i.m. injection of pilocarpine hydrochloride for stimulation. Tears were collected before and after PRK surgery, and then daily for 5 days, and every fourth day thereafter for 3 months. Both eyes underwent PRK treatment. One eye of each rabbit was treated as a control while the contralateral eye was treated with aprotinin, a serine protease inhibitor, over the first 7 days. PAA in the tear samples was measured by a spectrophotometric method using human plasminogen and chromogenic peptide substrate S-2251. For the eight control eyes after PRK, the PAA values were significantly lower (day 1) and higher (days 2 and 3) than the equilibrium PAA (p<0.001). The corneas remained clear in each of these control eyes. For the eight contralateral aprotinin-treated eyes after PRK, the PAA values on days 1-7 were significantly lower than the equilibrium PAA (p<0.001). All eight of these aprotinin-treated eyes developed corneal haze after 2 months. There was no significant difference (p=0.06) between control and aprotinin-treated eyes for the equilibrium PAA after 19 days. We conclude that a corneal wound healing abnormality (haze) develops in rabbit eyes after PRK when PAA levels are reduced using aprotinin for a week following PRK.     

Corneal epithelial healing after photorefractive keratectomy: analytical study

PURPOSE: To characterize the velocity of epithelial migration after photorefractive keratectomy (PRK) with 3 different corneal ablation patterns. SETTING: Department of Ophthalmology, Catholic University of Rome, Rome, Italy. METHODS: Fifteen patients (30 eyes) with mild to moderate myopia and with simple to compound myopic astigmatism were enrolled for this study. The surgical procedure consisted of standardized PRK with final smoothing performed using the Technolas Keracor 217C excimer laser. The reepithelialization process was evaluated at 0 hours, 20 hours, 40 hours, and 60 hours after surgery using a digital photo camera and custom software for measurement. Digital analysis of the images was performed. Corneal topographies were taken at 1 month, 3 months, 6 months, and 12 months after PRK. RESULTS: The mean speed of radial migration in the 10 eyes (33%) in the low spherical ablation group was 0.087 mm/h +/- 0.008 (SD). This was significantly higher than that found in the 10 eyes (33%) in the high spherical ablation group (mean speed 0.078 +/- 0.007 mm/h; P<.001) and in the 10 eyes (33%) in the cross-cylinder ablation group (mean speed 0.055 +/- 0.014 mm/h; P<.001). CONCLUSION: Analysis of the data shows that epithelial migration along the photoablated corneal surface depends on the ablation pattern. The epithelial sliding is highly influenced by local variations in the curvature of the stromal surface. The data demonstrate that faster epithelial wound healing after PRK is predictive of optimal visual performance.     

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.     

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。     

Penetration of ofloxacin and ciprofloxacin in aqueous humor after topical administration.

BACKGROUND AND OBJECTIVE: To compare the aqueous humor levels of 0.3% ofloxacin and 0.3% ciprofloxacin containing eyedrops in patients with healthy cornea. PATIENTS AND METHODS: Fifty patients with cataract were randomly assigned to have 0.3% ofloxacin containing eyedrop (25 patients) or 0.3% ciprofloxacin containing eyedrop (25 patients). Both drugs were repetitively instilled to each patient for 6 hours before the surgery. Aqueous samples were collected after penetrating the anterior chamber during cataract extraction and assayed by high-performance liquid chromatography method. RESULTS: The aqueous humor level of ofloxacin (1.43 +/- 0.26 microg/ml, mean +/- SEM) was significantly higher than that of ciprofloxacin (0.35 +/- 0.07 microg/ml) following the topical application (P < .0002). CONCLUSION: Aqueous humor penetration of topical ofloxacin is about 4 times higher than that of topical ciprofloxacin when the drugs are applied as described above.     

Epithelial scrape for photorefractive keratectomy overcorrection associated with induced regression

PURPOSE: To study the effect of combined corneal epithelial scrape and contact lens wear treatment on regression in eyes with symptomatic overcorrection after photorefractive keratectomy (PRK) or PRK retreatment. METHODS: Fifteen eyes had corneal epithelial scrape with a scalpel followed by soft contact lens wear for approximately 1 month. Eight of the eyes were treated 3-4 months after the laser procedure, and seven eyes were treated >4 months after laser treatment. Fifteen eyes that had the same level of PRK correction and monitored during the same interval after PRK were used as matched control eyes. RESULTS: Epithelial scrape was performed for mean spherical equivalent (SE) of +1.1+/-0.4 diopters (D) (range, +0.50 to +1.75 D) at mean 6.1+/-3.2 months after PRK or PRK retreatment. The SE in these eyes was +0.5+/-0.6 D (range, -0.25 to +1.25 D) 3 months after epithelial scrape and +0.4+/-0.5 D (range, -0.75 to +1.25 D) 6 months after scrape. The change in scraped eyes at 3 and 6 months compared to before scrape was statistically significant (p = 0.001 and p = 0.001, respectively). The change in mean SE at 6 months after scrape (-0.7+/-0.5 D) was significantly different than the change noted in matched control eyes that were not scraped (-0.1+/-0.2 D) over the same interval after the PRK or PRK retreatment procedure. The change in SE at 6 months after epithelial scrape was greater for the eyes scraped 4 months or less (mean, 3.6+/-0.5 months) after PRK (-0.9+/-0.3 D) than eyes scraped >4 months (9.0+/-2.6 months) after PRK (-0.4+/-0.5 D). This difference approached statistical significance (p = 0.06). CONCLUSIONS: Epithelial scrape and soft contact lens treatment for symptomatic overcorrection after PRK may induce regression and is more likely to be effective when performed <4 months after the primary PRK or PRK retreatment procedure.     

Effects of topical vitamin E on keratocyte apoptosis after traditional photorefractive keratectomy

PURPOSE: To evaluate the keratocyte apoptosis and effects of topical vitamin E on keratocyte apoptosis after photorefractive surgery. METHODS: Rabbits were divided into 7 groups, and all groups were compared with controls after epithelial scraping, epithelial scrape and photorefractive keratectomy (PRK) (traditional PRK), transepithelial PRK, production of a corneal flap with microkeratome and laser-assisted in situ keratomileusis (LASIK). The effects of topical Vitamin E treatment were investigated in the traditional PRK group. The terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay (to detect DNA fragmentation in situ) and light microscopy have been used to detect apoptosis in rabbit cornea. RESULTS: Transepithelial PRK induced minimal keratocyte apoptosis, less than in all other refractive surgical procedures. The greatest amount of keratocyte apoptosis was observed after traditional PRK (p = 0.001), therefore we tested the effects of topical vitamin E in this group. The number of apoptotic keratocytes significantly reduced after vitamin E therapy (p < 0.005). CONCLUSION: Keratocytes undergo apoptosis after refractive surgery in response to mechanical epithelial removal, preparing of corneal flap and excimer laser stromal photoablation. The topical application of vitamin E immediately after surgery can prevent keratocyte apoptosis, and this result suggests that free radicals may be partly responsible for keratocyte apoptosis after excimer laser keratectomy.     

准分子激光角膜切削术后转化生长因子β及Ⅰ、Ⅲ型胶原的免疫组化观察

目的观察准分子激光角膜切削术（ｐｈｏｔｏｒｅｆｒａｃｔｉｖｅｋｅｒａｔｅｃｔｏｍｙ,ＰＲＫ）术后,猴角膜愈合过程中角膜转化生长因子β（ｔｒａｎｓｆｏｒｍｉｎｇｇｒｏｗｔｈｆａｃｔｏｒｂｅｔａ,ＴＧＦβ）的表达,以及Ⅰ、Ⅲ型胶原的表达情况,探讨ＴＧＦβ与ＰＲＫ术后角膜愈合过程中Ⅰ、Ⅲ型胶原合成的关系。方法对３只（６只眼）恒河猴行ＰＲＫ治疗。输入－１０００Ｄ治疗程序,切削深度为１０３μｍ。分别于术后１、３及６个月行光镜、电镜及免疫组化检查。结果术后１个月,ＴＧＦβ在角膜上皮层染色阳性,上皮下也可见少量成纤维细胞染色阳性;３个月,角膜上皮染色减弱;６个月时染色呈阴性;对照组为阴性。Ⅰ、Ⅲ型胶原于术后１、３及６个月时均有较强的阳性染色,对照组Ⅰ型胶原染色阳性,Ⅲ型胶原染色阴性。结论ＴＧＦβ参与ＰＲＫ术后角膜的愈合过程,并且可能与术后角膜上皮下新生胶原中Ⅰ、Ⅲ型胶原的合成有关。     

Delayed epithelial healing following photorefractive keratectomy with mitomycin C treatment

Purpose: To evaluate the epithelial healing following photorefractive keratectomy (PRK) with mitomycin C (MMC) 0.02%. Methods: A total of 1520 eyes of 760 patients with myopia with spherical equivalent between ?1.5 and ?8.0 dioptres underwent PRK during 2004–2008. The epithelium was removed mechanically, and laser ablation was followed by topical application of MMC (0.02%) for 20 seconds. A therapeutic contact lens (TCL), kept in 4°C, was fitted and worn until complete epithelialization. Antibiotic, steroid and diclofenac drops were instilled during the healing phase. Steroid drops were used for 6–8 weeks and gradually reduced. The results were compared with a retrospective analysis of 500 myopic eyes which underwent PRK without MMC therapy during 2002–2004. Results: In 30 MMC treated eyes (2%), epithelial healing was delayed with a stellate defect which healed after 12–14 days. Another fifteen eyes (1%) revealed loose midperipheral epithelium and complete epithelialization took 10–14 days after scraping. Two of these eyes developed recurrent erosion treated by scraping and TCL. Seven eyes (0.5%) revealed delayed healing with paracentral epithelial plaques which were scraped and complete healing took 12–14 days. No final haze was found in the MMC‐treated eyes. In comparison, only 0.8% of the eyes which had undergone PRK without MMC revealed epithelial problems. Haze was found in 8% of these eyes. A statistically significant difference was found between the rate of epithelial problems of the two groups (p ≤ 0.002). Conclusions: MMC (0.02%) applied for 20 seconds post‐PRK was found to delay epithelial wound healing up to 14 days in 3.5% of patients with myopia compared to 0.8% of PRK eyes without MMC application. Final haze was not found despite delayed epithelialization because of MMC treatment.     

Corneal epithelial healing rates after topical nucleotides

Discrete 28mm2 epithelial lesions in paired rabbit corneas were treated four times daily with either vehicle alone or 10(-2)M or 10(-3)M Db cAMP in the presence or absence of either theophylline (10(-2)M) or epinephrine (5.5 x 10(-3)M). Cyclic GMP was also used either alone or with pilocarpine (1%). The lesion size was determined photographically at various intervals over 48 hours. No treatment regimen at the concentrations of cyclic nucleotides used had any influence on the rate of epithelial regrowth.     

Wound healing in rabbit corneas after photorefractive keratectomy and laser in situ keratomileusis

PURPOSE: To compare the wound-healing process in the rabbit cornea after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) with the same refractive correction. SETTING: Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. METHODS: Adult albino rabbits (N = 24) were used. One eye of each animal had PRK or LASIK with the same refractive correction. Each animal was killed after an interval of up to 6 months. The expression pattern of corneal stromal injury-related molecules with the 2 treatments were compared. Paraffin sections of the cornea were processed immunohistochemically for alpha-smooth muscle actin (alpha-SMA), collagen type IV [alpha1(IV)](2),alpha2(IV), and heat shock protein (HSP) 47 as well as other HSPs. Sections were also examined after hematoxylin and eosin or periodic acid-Schiff staining. RESULTS: Hematoxylin and eosin staining showed the central epithelium to be thick in PRK-treated corneas. The thick epithelium was restricted to the area around the corneal flap edge adhesion in LASIK-treated corneas at 3 months. Periodic acid-Schiff staining showed an absence of or interruption in the epithelial basement membrane in PRK-treated corneas for up to 6 months. Heat shock protein 47 was detected in keratocytes on day 3 but not after that in PRK-treated corneas. There was no difference in the expression of other HSPs. Alpha-smooth muscle actin was expressed in keratocytes repopulated in the central anterior cornea of PRK-treated corneas at 28 days. Keratocytes with immunoreactivity for these 2 proteins were not seen in LASIK-treated corneas. Collagen IV [alpha1(IV)](2),alpha2(IV) was not detected in either group of corneas. The central epithelium became transiently thicker in PRK-treated corneas. CONCLUSION: Keratocyte responses to laser stromal ablation were more marked in corneas treated with PRK than in those treated with LASIK.     

Late corneal perforation after photorefractive keratectomy associated with topical diclofenac: involvement of matrix metalloproteinases

OBJECTIVE: To report a case of a 50-year-old man who was initially seen with a corneal perforation in his right eye 2 months after a photorefractive keratectomy (PRK) procedure and to discuss the roles of topical diclofenac and matrix metalloproteinases (MMPs). DESIGN: Case report with tissue analysis. MAIN OUTCOME MEASURES: Ocular examination, diagnostic workup, surgical treatment, and histologic, immunofluorescent, zymography, and real time-polymerase chain reaction studies on corneal button. RESULTS: Slit-lamp examination of the right eye revealed a 4-mm diameter area of central corneal thinning with a 2-mm diameter perforation at its center. Predisposing factors included prolonged postoperative topical diclofenac therapy for more than 2 months and a 10-year history of well-controlled diabetes mellitus. An extensive diagnostic workup ruled out a systemic autoimmune disease. A penetrating keratoplasty was performed. Results of immunohistochemical studies of the corneal button showed stromal accumulation of temporary type III and IV collagens, MMP-3, and MMP-9 in the anterior wounded stroma and MMP-9 in the basal corneal epithelial cells of the leading edge. Differential activity and expression of MMP-2 and MMP-9 were found between the central and peripheral corneal buttons. CONCLUSIONS: Prolonged use of diclofenac and diabetes mellitus might be responsible for the corneal perforation after PRK in our patient. MMP-9 and MMP-3 might be involved in delayed wound closure and corneal melting.