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To investigate the effects of topical vitamin E and hydrocortisone acetate treatments on corneal healing response after -10.0 D photorefractive keratectomy (PRK) in rabbits.
Thirty-three New Zealand white rabbits were divided into four groups and -10 D PRK was performed under in vivo conditions. Following PRK, group 1 (n = 9) received no topical tr...
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... was no significant alteration in the corneal structures. The epithelium was composed of six to eight layers. The anterior stroma was uniform and the keratocyte density was minimally increased, 55.8% of keratocytes being located in the anterior half of the stroma (Fig. 2). The basement membrane displayed focal disruptions with hemidesmosomes (Fig. ...
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... Vitamin E is an antioxidant found in all tissues and reported to reduce keratocyte apoptosis after traditional PRK [62]. In rabbits, topical 1% vitamin E ointment has been shown to have a weak but statistically significant effect in reducing post PRK haze [63]. Therefore, topical vitamin A and E may be beneficial for preventing post PRK haze. ...
Photorefractive keratectomy (PRK) is a safe and popular corneal surgery performed worldwide. Nevertheless, there is potential risk of corneal haze development after surgery. Proper management of post PRK haze is important for good visual outcome. We performed a comprehensive review of the literature on the various risk factors and treatments for PRK haze, searching the PubMed, Google Scholar, SCOPUS, ScienceDirect, and Embase databases using relevant search terms. All articles in English from August 1989 through April 2023 were reviewed for this study, among which 102 articles were chosen to be included in the study. Depending on the characteristics of and examination findings on post PRK haze, different management options may be preferred. In the proposed framework, management of PRK haze should include a full workup that includes patient's subjective complaints and loss of vision as well as visual acuity, biomicroscopy, anterior segment optical coherence tomography, epithelial mapping, and Scheimpflug densitometry. Topical steroid treatment for haze should be stratified based on early- or late-onset haze. Mechanical debridement or superficial phototherapeutic keratectomy (PTK) may be used to treat superficial corneal haze. Deep PTK and/or PRK can be used to treat deep corneal haze. Mitomycin-C and topical steroids are prophylactic post-surgery agents to prevent recurrence of haze.
... 12 Corticosteroids have also shown to decrease corneal wound strength in both animal and human studies. [13][14][15] Additionally, Bourcier et al. 16 have found that dexamethasone is associated with the apoptosis and necrosis of keratocytes, eventually decreasing viable cells and integrity of corneal structure. Despite these adverse effects, corticosteroids, such as dexamethasone, have proven their anti-inflammatory effect in postoperative settings in patients undergoing strabismus surgery. ...
Abstract
Objective: To compare outcomes of diclofenac versus dexamethasone in patients after strabismus surgery. Data Sources: A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search was conducted on MEDLINE, EMBASE, EMCARE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL).
Study Selection: All randomized controlled trials (RCTs) comparing the outcomes of diclofenac versus dexamethasone poststrabismus surgery were included.
Data Extraction and Synthesis: An extraction spreadsheet for data collection and Review Manager 5.3 were used for data analysis based on the fixed and random effects models.
Outcomes: Discomfort, inflammation, chemosis, conjunctival gap, and intraocular pressure (IOP) were primary outcome measures. Secondary outcomes included conjunctival congestion and injection, discharge, and drop intolerance. Fixed and random effects models were used for the analysis.
Results: Five RCTs enrolling 248 subjects were enrolled. At week 2 postoperatively, there was a significant difference favoring diclofenac over dexamethasone in terms of discomfort (mean difference [MD]=-0.37, P=0.02), conjunctival inflammation (MD=-0.16, P=0.02), conjunctival chemosis (MD=-0.16, P=0.04), and postoperative conjunctival gap (MD=-0.17, P=0.002). In terms of IOP, there were no significant dif- ferences. However, no statistically significant differences were noted at weeks 1 and 4 postoperatively. For secondary outcomes, dexamethasone had significantly improved conjunctival congestion; however, diclofenac had significantly less injection at the site of muscle attachments at week 2. No significant difference was noted in terms of discharge and drop intolerance.
Conclusion: Diclofenac is comparable to dexamethasone when used following strabismus surgery. However, a significant difference favoring diclofenac in terms of discomfort, inflammation, conjunctival chemosis, and conjunctival gap was only noted at 2 weeks postoperatively. The authors suggest conducting further studies to support the effectiveness of diclofenac as an alternative to corticosteroids following strabismus surgery.
Keywords: strabismus, diclofenac, dexamethasone, inflammation, chemosis, intraocular pressure
... In rabbit models, the topical application of a variety of molecules is able to promote the corneal repair process leading to a better wound healing; among the tested factors, can be mentioned the plasma rich in growth factors (PRGF-Endoret) [10], the ascorbic acid [11], the nerve growth factor (NGF) in combination with docosahexaenoic acid (DHA) [12], the vitamin E and hydrocortisone acetate [13], and finally the basic fibroblast growth factor (bFGF) [14,15] can be mentioned. Moreover we previously showed that, in transgenic mice, topical cytochrome c peroxidase [16], bFGF alone [17], or in combination with cytochrome c [18] and oral administration of L-cysteine [19] significantly accelerates epithelial healing after excimer photoablation. ...
... Indeed, the use of free radical scavengers, such as ubiquinone Q10 [35] or vitamin E [13], are effective in preventing corneal keratocyte apoptosis and, also, in stimulating corneal reepithelization. Notably, the immediate post operative use of ascorbic acid significantly reduced lipid peroxidation oxygen radical-mediated tissue damage [11], suggesting that topical ascorbic acid could be considered a complementary treatment in the pharmacological modulation after excimer laser corneal surgery [13]. ...
... Indeed, the use of free radical scavengers, such as ubiquinone Q10 [35] or vitamin E [13], are effective in preventing corneal keratocyte apoptosis and, also, in stimulating corneal reepithelization. Notably, the immediate post operative use of ascorbic acid significantly reduced lipid peroxidation oxygen radical-mediated tissue damage [11], suggesting that topical ascorbic acid could be considered a complementary treatment in the pharmacological modulation after excimer laser corneal surgery [13]. In this scenario, it is plausible that L-cysteine supplementation exhibits beneficial effects on corneal integrity by preventing an excessive oxidative state due to PRK surgery and thus by reducing the epithelial prolonged inflammation it favors a faster stromal recovery. ...
We aimed at evaluating the long-term effects of l-cysteine oral supplementation to basic fibroblast growth factor (bFGF) eye-drops on corneal re-epithelization and transparency in myopic patients subjected to photorefractive keratectomy (PRK). Forty patients subjected to bilateral PRK for myopia were enrolled and randomly divided into two groups receiving an additional therapy together with the standard postoperative treatment consisting in local tobramycin 0.3%, dexamethasone 0.1%, diclofenac 0.1%, and 0.2% hyaluronate. Group 1 included 20 patients (11 males and 9 females; 34.09 ± 8 years of age) receiving only bFGF eye-drops (10 μg/10 μL) four times a day for 7 days starting from the day of surgery; Group 2 included 20 patients (12 males and 8 females; 37.35 ± 11.5 years of age) who were postoperatively administered with topical basic fibroblast growth factor (bFGF; 10 μg/10 μL) four times a day for 7 days plus oral l-cysteine supplementation (500 mg/capsule) once a day for 15 days, starting 7 days before PRK. Patients were followed-up for 12 months. Clinical ophthalmologic parameters were recorded for all the 80 examined eyes. The corneal transparency was evaluated in vivo by slit lamp and confocal microscopy. The data showed that: (a) the corneal haze occurred in a smaller percentage of the patients who were postoperatively administered with topical bFGF plus oral l-cysteine supplementation (Group 2) compared to patients who received only bFGF (Group 1); (b) at 6 months of follow-up, the stromal mean image brightness of the patients belonging to Group 2 was significantly lower than that of the Group 1 (p < 0.03), and, interestingly, the difference was even more evident at 12 month from the treatment (p < 0.001). Moreover, the final mean of the spherical equivalent refraction was −0.06 ± 0.2 D in Group 1 and −0.08 ± 0.3 D in Group 2, whereas the final uncorrected distance visual acuity (UDVA) was equal or superior to 20/25 in 100% of eyes in both Group 1 and 2. Post refractive patients can benefit from the administration of l-cysteine before the surgery and in association with bFGF in the early postoperative period, showing a faster corneal re-epithelization able to prevent corneal haze in the long-term recovery.
... Additionally, more rapid epithelial healing has been shown to limit postoperative problems such as haze formation.[383940] Several growth factors, vitamins and amino acids have also been shown to have a primary and active role in corneal re-epithelialization after corneal injury.[414243444546] These substances improve corneal haze and speed the complex process of corneal epithelial healing.[47] ...
... Altered epithelial repair induces excessive and disorganized stromal healing, with alterations to the corneal transparency and impairments in visual function. The degree and extent of keratocyte apoptosis also varies with the type of overlying epithelial injury, and can be influenced by the surgical technique and drugs.[121314151617181920212223242526272829303132333435363738394041424344454647] Therefore, rapid re-epithelialization of the cornea would likely promote wound healing of the underlying stroma with minimal cell apoptosis.[38] ...
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.
... Antioxidants and free radical scavengers have been reported to protect the cornea from the harmful effects of free radicals [22,23]. The protective effects of ascorbic acid and vitamin E after PRK have been demonstrated in previous studies [23,24]. Ubiquinone Q 10 (coenzyme Q 10 , CoQ 10 ) is a well-known electron transporter in complexes I (NADH-ubiquinone oxidoreductase), II (succinateubiquinone oxidoreductase), and III (ubiquinone-cytochrome c oxidoreductase) of the mitochondrial respiratory chain [25,26]. ...
Dilute ethanol (EtOH) is a widely used agent to remove the corneal epithelium during the modern refractive surgery. The application of EtOH may cause the underlying corneal fibroblasts to undergo apoptosis. This study was designed to investigate the protective effect and potential mechanism of the respiratory chain coenzyme Q(10) (CoQ(10)), an electron transporter of the mitochondrial respiratory chain and a ubiquitous free radical scavenger, against EtOH-induced apoptosis of corneal fibroblasts. Corneal fibroblasts were pretreated with CoQ(10) (10 µM) for 2 h, followed by exposure to different concentrations of EtOH (0.4, 2, 4, and 20%) for 20 s. After indicated incubation period (2-12 h), MTT assay was used to examine cell viability. Treated cells were further assessed by flow cytometry to identify apoptosis. Reactive oxygen species (ROS) and the change in mitochondrial membrane potential were assessed using dichlorodihydrofluorescein diacetate/2',7'-dichlorofluorescein (DCFH-DA/DCF) assays and flow-cytometric analysis of JC-1 staining, respectively. The activity and expression of caspases 2, 3, 8, and 9 were evaluated with a colorimetric assay and western blot analysis. We found that EtOH treatment significantly decreased the viability of corneal fibroblasts characterized by a higher percentage of apoptotic cells. CoQ(10) could antagonize the apoptosis inducing effect of EtOH. The inhibition of cell apoptosis by CoQ(10) was significant at 8 and 12 h after EtOH exposure. In EtOH-exposed corneal fibroblasts, CoQ(10) pretreatment significantly reduced mitochondrial depolarization and ROS production at 30, 60, 90, and 120 min and inhibited the activation and expression of caspases 2 and 3 at 2 h after EtOH exposure. In summary, pretreatment with CoQ(10) can inhibit mitochondrial depolarization, caspase activation, and cell apoptosis. These findings support the proposition that CoQ(10) plays an antiapoptotic role in corneal fibroblasts after ethanol exposure.
... Oxygen free radical-induced tissue damage following PRK is well documented.9–17 ...
To evaluate the role of prepared basic fibroblast growth factor (bFGF) and cytochrome c peroxidase (CCP) combination eyedrops in corneal epithelial healing of transgenic mice (B6(A)-Rpe(rd12)/J) after excimer laser photoablation.
In this prospective study, 216 eyes of 108 mice underwent bilateral photorefractive keratectomy. We considered 4 groups: A, B, C, and D. Group A received standard topical postoperative therapy with tobramycin, diclofenac, and dexamethasone eyedrops plus CCP at 3 drops per day for a week or until corneal re-epithelialization was achieved. Group B received standard topical postoperative therapy plus bFGF eyedrops and phosphate-buffered saline (PBS) 3 drops per day for a week or until corneal re-epithelialization was complete. In group C, 1 eye received standard topical postoperative therapy plus CCP eyedrops, bFGF eyedrops, and PBS 3 drops per day for a week or until corneal re-epithelialization was complete. Control eyes (group D) received a standard topical postoperative therapy plus placebo eyedrops. Mice were followed-up for a week from the day after the surgery to evaluate the rate of corneal re-epithelialization.
Data were analyzed by ANOVA using the XLSTAT 2010 software. Eyes in group A, B, and C healed completely before the fifth postoperative day, achieving, respectively, a re-epithelialization time of 92 hours ± 10 SD, 90 hours ± 12 SD, and 86 hours ± 12 SD. Group D had a re-epithelialization time of 121 hours ± 8 SD (P < 0.05). No side effects or toxic effects were documented.
Results suggest that re-epithelialization after phototherapeutic keratectomy can benefit from topical therapy with CCP/bFGF combination eyedrops. Further clinical studies are needed to evaluate the long-term effectiveness of these eyedrops to prevent corneal haze.
... Several other agents such as synthetic inhibitors of metalloproteinase, cyclosporine-A, vitamin E, diclofenac, etc. have shown some benefit in animal studies. However, their high toxicity combined with other deleterious side effects limit their use in humans [98][99][100]. Nerve growth factor and amniotic membrane have also been reported to control corneal scar and corneal ulcer formation. ...
... Phototherapeutic keratectomy, a laser surgical technique, has also been used to treat corneal scarring resulting from gunpowder explosion but leads to undesirable side effects including hyperopic shift and astigmatism among others. The complications and, in some cases, toxicity of current practices in the management of corneal scarring illustrates the inherent risks of these treatments and advocates for the development of safer, improved pharmacologic agents in reducing corneal haze without serious side effects [98][99][100]. ...
Transforming growth factor-beta (TGFbeta) is a pleiotropic multifunctional cytokine that regulates several essential cellular processes in many parts of the body including the cornea. Three isoforms of TGFbeta are known in mammals and the human cornea expresses all of them. TGFbeta1 has been shown to play a central role in scar formation in adult corneas whereas TGFbeta2 and TGFbeta3 have been implicated to play a critical role in corneal development and scarless wound healing during embryogenesis. The biological effects of TGFbeta in the cornea have been shown to follow Smad dependent as well as Smad-independent signaling pathways depending upon cellular responses and microenvironment. Corneal TGFbeta expression is necessary for maintaining corneal integrity and corneal wound healing. On the other hand, TGFbeta is perhaps the most important cytokine in the pathogenesis of fibrotic disease in the cornea. Although the transformation of keratocytes to myofibroblasts induced by TGFbeta is largely believed to cause corneal fibrosis or scarring, the precise molecular mechanism(s) involved in this process is still unknown. Currently no drugs are available to treat corneal scarring effectively without causing significant side effects. Many approaches to treat TGFbeta-mediated corneal scarring are under investigation. These include blocking of TGFbeta, TGFbeta receptor, TGFbeta function and/or TGFbeta maturation. Other strategies such as modulating keratocyte proliferation, apoptosis, transcription and DNA condensation are also being investigated. The potential of gene therapy to neutralize the pathologic effects of TGFbeta has also been demonstrated recently.
... 17 Topical corticosteroids, even at a relatively low dose, have been shown to inhibit corneal wound strength in rabbits and humans. [18][19][20] Cortisol is a corticosteroid hormone that is produced by the adrenal cortex. The most well-known of various synthetic forms of cortisol is a natural metabolic intermediary of cortisol named hydrocortisone, which we used in our study as a steroid agent. ...
To investigate the change in biomechanical properties of the cornea induced by high-dose hydrocortisone.
The influence of hydrocortisone was investigated in 12 fresh porcine corneas incubated in culture medium of 2.5 muM of hydrocortisone for 7 days. Twelve additional porcine corneas incubated in culture medium without hydrocortisone for the same time served as the control group. Strips of cornea were cut and the stress-strain relationship was measured in a biomaterial tester. Young's modulus was calculated.
After incubation, the thickness of the cornea was 1120+/-130 mum in the control group and 1320+/-90 mum in the hydrocortisone group. The hydrocortisone-treated corneas were 18% thicker compared to the control corneas. However, the difference in the biomechanical stress value at 10% strain was significantly larger. In the control group, the stress value measured 122+/-40 kPa, and in the hydrocortisone group, it measured 77+/-19 kPa (P=.003), representing a reduction of the corneal stiffness by 37% due to hydrocortisone treatment. Young's modulus was reduced by 42.8% from 2.90+/-1.10 MPa in the control group to 1.66+/-0.49 in the hydrocortisone group.
Hydrocortisone is a modulating factor of the biomechanical properties of the cornea. The significance of the cortisol status of the patient and its influence on the biomechanical stability of the cornea should be considered in the development of keratectasia in keratoconus or after refractive surgery.
... However, steroids are almost the mainstay of treatment and core of modulation of wound healing after surface ablation. In a previous study we have demonstrated that steroids are more potent than other agents in suppressing various steps of wound healing response (40). Furthermore, steroids are widely used in the early postoperative period after surface ablation for their advantageous effect. ...
To evaluate the effect of topical N-acetylcysteine (NAC) on interleukin 1-alpha (IL-1alpha) levels in tear fluid after myopic laser subepithelial keratectomy (LASEK) and its possible role in modulating corneal wound healing.
Twenty-six eyes of 13 patients who underwent myopic LASEK were divided into 2 groups. Group 1 (n=10 eyes) was used as a control group. All patients received topical lomefloxacin and dexamethasone postoperatively. Additionally, patients in Group 2 received topical NAC for 1 month postoperatively. Tear fluid samples were collected with microcapillary tubes preoperatively, on the first and on the fifth postoperative day, and the release of IL-1alpha in tear fluid was calculated. Haze grading and confocal microscopic examination were performed at 1 and 3 months postoperatively.
The mean IL-1-alpha release values were 0.285-/+0.159 pg/min in Group 1 and 0.235-/+0.142 pg/min in Group 2 preoperatively. In Group 1, the values were 0.243-/+0.155 pg/min on day 1 and 0.164-/+0.125 pg/min on day 5. In Group 2, the mean IL-1alpha release values were 0.220-/+0.200 pg/min on day 1 and 0.080-/+0.079 pg/min on day 5. The difference between the groups was significant only for day 5 (p<0.05). Mean corneal haze score and grey scale value in confocal microscopy were significantly higher (p<0.05) in Group 1 at 1 month. However, at 3 months there was no difference between groups (p>0.05).
NAC seems to have an additive effect to steroids in suppressing IL-1alpha levels in tear fluid and may be clinically advantageous in modulating corneal wound healing during the early postoperative period after LASEK.
... 41 Hydrocortisone acetate with vitamin E was shown to reduce the wound-healing response in rabbits after PRK. 42 The natural depression of uPA in the pregnant rabbit ( Fig. 1) and the artificial inhibition of uPA activity in the aprotinintreated eyes ( Fig. 1 and Csutak et al. 17 ) correlate with the occurrence of corneal haze after PRK. The pattern of depressed uPA activity in these eyes for several days after PRK mimics that in human eyes in which haze develops after PRK. 5 In contrast, post-PRK clear corneas follow a pattern of elevated uPA activity over that same period ( Fig. 1 and Csutak et al. 5,17 ). ...
To observe the effect of urokinase-type plasminogen activator (uPA) on the development of subepithelial haze after photorefractive keratectomy (PRK) and to assess pregnancy as a risk factor for haze.
In 30 rabbits, both eyes of 27 were subjected to PRK and both eyes of 3 served as the nonsurgical control. In the first part of the experiment, for 7 days after PRK, three rabbits (one was pregnant) received aprotinin in one eye and no aprotinin in the contralateral eye. uPA activity was measured by a spectrophotometric method from tear samples in these eyes. In the second part, for 5 days after PRK, 24 rabbits (8 were pregnant) were treated with uPA in one eye and no uPA in the contralateral eye. Haze grading was performed according to the system of Hanna.
In the first experiment, the aprotinin-treated eyes and the aprotinin-untreated eye of the pregnant rabbit showed development of haze. In the second, there were clear corneas in 24 of 24 uPA-treated eyes and in 15 of 24 uPA-untreated eyes. Post-PRK haze formed in 9 of 24 uPA-untreated eyes (7 of the 9 haze observations in pregnant rabbits). Within the uPA-untreated group, haze formed in corneas of 7 of 8 pregnant versus 2 of 16 nonpregnant rabbits. There was a strong association between the uPA treatment and clear corneas (P = 0.003) and between pregnancy and haze (P = 0.002).
The present results suggest that pregnancy is a risk factor for post-PRK haze in untreated rabbit eyes and that uPA is effective in preventing the occurrence of haze.
