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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 4  |  Page : 1201-1206

Evaluation of corneal haze after transepithelial photorefractive keratectomy


Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission29-Apr-2020
Date of Decision10-Jun-2020
Date of Acceptance15-Jun-2020
Date of Web Publication24-Dec-2020

Correspondence Address:
Islam F. F. Mohamad
Zagazig
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_121_20

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  Abstract 


Background
Transepithelial photorefractive keratectomy (t-PRK) has been associated with diminished wound healing response, hence less refractive regression and haze, compared with other techniques of epithelial removal in PRK.
Objectives
To evaluate the corneal haze after t-PRK.
Patients and methods
This prospective highly selectional observational study involved 100 eyes of patients with simple myopia and mixed myopia with astigmatism who underwent t-PRK to correct their vision. Both males and females were included who were age and sex matched.
Results
The results showed improvement of visual haze along the follow-up period. Comparison of visual haze between follow-up period 1 week after t-PRK and the end of the follow-up period (6 months) revealed the following: after 1 week, mean ± SD visual haze was 1.22 ± 1.19, which decreased to 0.8 ± 1.05 after 1 month, decreased to 0.325 ± 0.605 after 3 months, and then decreased to 0.12 ± 0.356 after 6 months. The results showed a statistically highly significant difference (P < 0.001). Preoperative visual acuity, refractive error, ablation depth, and residual stromal tissue showed a significant correlation with corneal haze postoperatively.
Conclusion
Preoperative visual acuity, refractive error, ablation depth, and residual stroma can induce corneal haze postoperatively, but most of the corneal hazes disappear with time. However, some need surgical interference.

Keywords: corneal haze, evaluation, myopia, transepithelial photorefractive keratectomy


How to cite this article:
Ellakwa AF, Badawy NM, Mohamad IF. Evaluation of corneal haze after transepithelial photorefractive keratectomy. Menoufia Med J 2020;33:1201-6

How to cite this URL:
Ellakwa AF, Badawy NM, Mohamad IF. Evaluation of corneal haze after transepithelial photorefractive keratectomy. Menoufia Med J [serial online] 2020 [cited 2021 Apr 19];33:1201-6. Available from: http://www.mmj.eg.net/text.asp?2020/33/4/1201/304479




  Introduction Top


Since the advent of excimer laser technology more than 20 years ago, photorefractive keratectomy (PRK) has been used extensively in the treatment of myopia. Despite its efficacy, surface ablation of the cornea has a risk for complications of corneal haze and opacification because of keratocyte activation, apoptosis, and the over-proliferation of myofibroblasts after surgery. Although studies have shown that the use of adjuvant intraoperative mitomycin-C (MMC) diminishes this risk, persistent postoperative corneal haze remains a visually debilitating complication of PRK[1].

PRK has also remained the refractive surgery of choice of some ophthalmologist in some situations, despite the advent of the laser in-situ keratomileusis (LASIK) and other advances in surface corneal ablation techniques because PRK does not carry the risk for traumatic flap-related complications[2].

Clinical studies comparing PRK and LASIK have yielded controversial results in terms of postoperative pain, speed of visual recovery, and wound healing[3].

Transepithelial photorefractive keratectomy (t-PRK) has been also associated with diminished wound healing response, hence less refractive regression and haze, compared with other techniques of epithelial removal in PRK[4].

Buzzonetti et al.[5] and Luger et al.[6] reported that t-PRK is as safe and effective as traditional PRK for myopic correction with a minimal hyperopic shift. Ghadhfan et al.[7] compared the refractive outcomes and complications of LASIK, t-PRK, traditional PRK, and laser-assisted subepithelial keratomileusis (LASEK). They detected slightly better visual results after t-PRK than after LASEK and the others, but the MMC application was higher in t-PRK-treated eyes. However, after a long-term experience with PRK, ocular discomfort and slow visual recovery remain the negative factors[8].

t-PRK limits initial keratocyte apoptosis and thus reduces subsequent repopulation of activated stromal keratocytes and wound healing response[9]. Compared with traditional PRK, t-PRK induces significantly less haze[10].

To date, few studies have assessed the refractive outcomes of PRK and the incidence of post-PRK corneal haze. Furthermore, most of these studies had a relatively limited sample size[11].

This study aimed to evaluate the corneal haze after t-PRK.


  Patients and Methods Top


This prospective highly selectional observational study involved 100 eyes of myopic patients. The study was done at Egyptian Lasik Group, Zagazig, and El-Hekma Eye Center, Shebin El Kom, Menoufia, in the period from June 2017 to January 2019.

Before beginning of the study and following the local regulations, the protocol and all corresponding documents were declared for ethical purposes and were approved by the Institutional Review Board of the Ophthalmology Department, Menoufia University.

Inclusion criteria

The following were the inclusion criteria: age of patients more than 18 years old, both sexes, myopic patients up to −8.0 D and/or astigmatism up to −5.0 D, patients with simple myopia and mixed myopic astigmatism with myopia, patients eligible for trans-PRK surgery after topographic (Pentacam; OCULUS Inc., Arlington, Texas, USA) examination with central corneal thickness (CCT) more than 400 μm and K reading above 44 D, absence of any ocular disease, and ability to sign an informed consent and understand the postoperative instructions.

Exclusion criteria

Patients who have cataract or glaucoma, patients with very high myopic error (>−8.0 D) and/or astigmatism. [>−5.0 D], patients with residual corneal tissue less than 400 μm, patients with diabetic retinopathy or other retinal diseases, patients with amblyopia of one or two eyes, patients with previous intraocular surgery, patients with elevated intraocular pressure, pregnant women and women in the childbearing period, uncooperative patients, and inability to give informed consent.

Technical design

Best-corrected visual acuity (BCVA) was measured in Snellen and log MAR equivalent. Intraocular pressure measurement was done by applanation tonometer (Keeler Instruments Inc., 3222 Phoenixville Pike, Malvern, Philadelphia 19355, US, England). Anterior segment examination was done by slit-lamp biomicroscopy (Haig Schteriet, Germany). Angle examination was done by Gonioscopy (Keeler Inc.). Posterior segment examination was done by indirect ophthalmoscopy (Keeler Inc.) and slit-lamp biomicroscopy with a non-contact + 90 D lens. Corneal topography was examined using Scheimpflug imaging technology by Pentacam camera (Pentacam; OCULUS Inc.).

The following steps were performed: topical anesthesia was induced using 0.4% Benoxinate HCL. Sterilization was done with povidone iodine 10% for the eyelids and povidone iodine 5% eye drops in the conjunctival cul-de-sac. Application of sterile drapes was done. Opening of the eye was done by the eye speculum. The epithelium was removed automatically by laser in the trans-PRK group. Laser ablation was then applied after introducing the refractive error data using the Abbot Visx S4 system and Schwind Amaris 500 system. Then antibiotic drops and contact lens are applied for 3–5 days. Steroid, non-steroidal anti- inflammatory eye drops, and tear substitutes were applied.

The patients were followed up after 1 day, 1 week, 2 weeks, 1 month, 3 months, and 6 months. In each visit, the following was done: visual acuity, autorefractometer reading, and slit-lamp examination.

Statistical analysis

The collected data were subjected to revision, and the collected data were coded, processed, and analyzed using the Statistical Package of Social Science (SPSS) program for Windows (standard version 22). The full detailed form is SPSS20 (IBM, Armonk, New York, USA). The normality of data was first tested with a one-sample Kolmogorov–Smirnov test.

Qualitative data were described using the number and percent. Association between categorical variables was tested using the χ2 test. Continuous variables were presented as mean ± SD. Student t test was used to compare two means, whereas the two paired groups were compared with paired t test. Sensitivity, specificity, predictive value for positive, predictive value for negative, and accuracy were calculated at 95% confidence interval to measure the validity.

For all the aforementioned statistical tests done, the threshold of significance is fixed at 5% level (P value). The results were considered nonsignificant when the probability of error is more than 5% (P > 0.05), significant when the probability of error is less than 5% (P ≤ 0.05), and highly significant when the probability of error is less than 0.1% (P ≤ 0.001).


  Results Top


This study involved 100 eyes of myopic patients. They comprised 35 males, with age ranging from 18 to 58 years and mean ± SD of 29.8 ± 5.78 years, and 65 females, with age ranging from 18 to 46 years and mean ± SD of 26.3 ± 9.42 years. Both males and females were age matched (P > 0.05) [Table 1].
Table 1: Demographic data of the studied patients

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The mean BCVA of the patients was 0.274 ± 0.227 preoperatively and corrected to 0.92 ± 0.1223 postoperatively (P < 0.001) [Table 2]. A spherical error was 2.475 ± 2.014 and cylinder error was 1.496 ± 1.224, which were corrected to 0.08 ± 0.001 and 0.025 ± 0.000, postoperatively, respectively. The results were statistically highly significant (P < 0.001) [Table 2].
Table 2: Visual acuity (decimal values) and refractive error of the studied groups

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Postoperative corneal haze in the follow-up period was as follows: after 1 week had a mean ± SD of 1.22 ± 1.19, which decreased to 0.8 ± 1.05 after 1 month, decreased to 0.325 ± 0.605 after 3 months, and then decreased to 0.12 ± 0.356 after 6 months. The results showed a highly statistically significant difference (P < 0.001) [Table 3].
Table 3: Postoperative corneal haze in the follow-up period

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Linear regression curve showed the correlation coefficient between preoperative visual acuity and incidence of corneal haze was r=−0.5129 (P < 0.01), between preoperative spherical error and incidence of corneal haze was r = 0.3897 (P < 0.05), between preoperative cylindrical error and incidence of corneal haze was r = 0.4925 (P < 0.01), between preoperative CCT and incidence of corneal haze r = 0.0557 (P > 0.05), between ablation depth and incidence of corneal haze was r = 0.6428 (P < 0.01), and between postoperative CCT and incidence of corneal haze was r=−0.3708 (P < 0.05) [Figure 1].
Figure 1: Linear regression curve.

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  Discussion Top


In our study, the epithelium was removed using the excimer laser, which we preferred owing to the homogeneous and uniform epithelial removal. Epithelial removal using laser has a superior effect on postoperative pain and subepithelial opacification[12].

In a study that compared the visual outcomes and safety of t-PRK and conventional PRK in eyes with low to moderate myopia, Naderi et al.[13] found that t-PRK was superior to conventional PRK in terms of improving safety and efficacy indices and visual acuity.

Preoperative BCVA in the patients compared with postoperative BCVA showed a highly statistically significant difference. Spherical and cylindrical errors postoperatively showed marked improvement in refraction, as they showed a statistically highly significant difference.

In agreement with these results, Mounir et al.[14] showed significant improvement in UCVA with a high safety index. This is particularly significant because their patients were high myopes in a high ultraviolet environment and were followed for at least 1 year. In their study, postoperative refraction was stable, with no statistically significant regression recorded during 12 months of follow-up. This finding is in agreement with that of Kaluzny et al.[15] who compared t-PRK and alcohol-assisted PRK in eyes with moderate myopia and compound myopic astigmatism correction and reported that the mean refractive spherical equivalent (SE) was stable during 3 months of follow-up. An old study by Buratto and Ferrari[16] found different results, as they found 29 of 40 eyes treated by PRK showed regression of myopia by 6 months after surgery.

Adib-Moghaddam et al.[17] reported a high degree of safety and visual improvement after t-PRK in patients with myopia up to − 8.75 D during 18 months of follow-up.

A comparison of corneal haze between the follow-up period 1 week after trans-PRK and the end of the follow-up period (6 months) showed a very highly statistically significant difference.

Correlation coefficient (r) between preoperative visual acuity and incidence of corneal haze showed inverse (negative) correlation as the increase in visual acuity preoperatively decreased the incidence of corneal haze postoperatively. The results showed statistically highly significant negative correlations.

In agreement with these results, Vinciguerra et al.[18] reported better postoperative visual acuity results with a platform equipped with smart-pulse technology compared with a conventional platform of single-step t-PRK in myopic eyes.

In contrast to our results, Adib-Moghaddam et al.[19] stated that haze induction was not significantly different in t-PRK compared with conventional PRK or LASIK; however, they added that less pain and faster re-epithelialization and visual rehabilitation was achieved compared with a convenient platform for myopia.

Aslanides et al.[20] reported that the visual acuity and refraction results were comparable between conventional and t-PRK. For the correction of high myopia, reverse single-step t-PRK resulted in better visual acuity outcomes compared with LASIK and PRK. However, other clinical outcomes were comparable across three groups[20].

Correlation coefficient (r) between preoperative spherical error and incidence of corneal haze showed a positive correlation as the increase in spherical error preoperatively increased the incidence of corneal haze postoperatively. The results showed a statistically significant positive correlation (r = 0.3897, P < 0.05). Moreover, the correlation between preoperative cylindrical error and incidence of corneal haze showed positive correlation as the increase in cylindrical error preoperatively increased the incidence of corneal haze postoperatively. The results showed statistically highly significant positive correlations.

In contrary to these results, Mounir et al.[14] found the predictability of the t-PRK group demonstrates good refractive predictability at a 1-year follow-up (84.52%). Moreover, Dausch et al.[21] investigated the clinical outcomes of PRK for myopia exceeding − 8.00 D using a standard or aspherical optimized profile in 100 eyes and demonstrated high predictability over a follow-up duration of 1 year. However, another study by Hashemi et al.[22] found the results of PRK with MMC for the correction of myopia more than 7.0 D, and baseline indices were not statistically significant at 6 months after surgery compared with LASIK. Furthermore, they also examined that visual outcomes and satisfaction among patients of PRK and femtosecond LASIK. They found the efficacy indexes of the femto-LASIK and PRK groups were 1.00 and 0.82, respectively. The predictability of the procedures was 92.1 and 64.9%, respectively.

Overcorrection and undercorrection can occur during t-PRK similar to other keratorefractive laser surgeries[17].

Correlation coefficient (r) between preoperative CCT and incidence of corneal haze showed no correlations as the increase in CCT preoperatively does not affect the incidence of corneal haze postoperatively. The results were statistically nonsignificant. Correlation between postoperative CCT and incidence of corneal haze showed negative correlations as the increase in CCT postoperatively decreases the incidence of corneal haze. The results showed a statistically significant difference.

Eyes with higher keratometry (K) values, CCT, and CCT to SE ratio are ablated with larger optical zones (OZs)[17]. Considering higher OZs is expected to decrease the risk for postoperative regression and defective visual function[23]. The advantage of higher OZs will be more important for eyes at risk for achieving suboptimal postoperative outcomes, such as those with higher preoperative corneal curvatures and attempted refraction[19].

The achieved OZ is influenced by the corneal epithelial thickness and the amount of refractive correction attempted. Reduced OZs might lead to insufficient ablation and undercorrection. On the contrary, large OZs cause tissue waste and consequent overcorrection. Furthermore, small OZs carry the risk for decentration followed by deterioration of corrected distance visual acuity. Small OZs also create a harsh margin where the ablated area sharply reaches the nonablated area, which results in more aggressive tissue regeneration and regression[24].

Adib-Moghaddam et al.[17] considered a combination of K values, CCT, and the ratio of CCT to SE for determination of OZ in their modified nomogram of refined single-step t-PRK.

Correlation coefficient (r) between ablation depth and incidence of corneal haze showed positive correlation as the increase in ablation depth increases the incidence of corneal haze. They were statistically highly significant positive correlations.

When the epithelium is removed before stromal ablation, the irregularity will be exposed in mechanical de-epithelization. The smoother stromal surface in t-PRK results in less incidence of postoperative haze induction[19]. Consequently, Aslanides et al.[20] reported faster epithelial healing and less haze as well as less pain after reverse single-step t-PRK compared with LASEK in patients with myopia.

Mosquera and Awwad[24] quantified the refractive implication of t-PRK and noted that it could result in wasted tissue, a reduced OZ, and additional refractive error. They concluded that in normal, not previously treated, nonpathologic corneas, the refractive outcome of t-PRK is theoretically equal to standard PRK.

MMC is an alkylating agent that inhibits cell growth. Studies found it to be useful in preventing haze induction and increasing efficacy and predictability of treating varying degrees of myopia and hyperopia by PRK[25]. Nevertheless, some clinical and experimental studies demonstrated the cytotoxic effects of MMC application on corneal endothelium[26],[27]. However, it has been suggested that reducing the application time and lowering the dose of MMC could be sufficient to prevent corneal scarring and subsequent corneal haze[25].

Several possible reasons could justify the less incidence of haze induction in t-PRK compared with other modalities of PRK. Transepithelial laser-assisted ablation of the cornea results in lower keratocyte loss and inflammatory response compared with the conventional modalities of PRK[28]. It also produces a smoother and more uniform stromal bed contour compared with mechanical PRK[29], which is more emphasized in reverse and smart-pulse technology improvements. The reverse sequence of stroma-epithelium ablation in reverse t-PRK promotes a soothing effect of the epithelium over stromal irregularities. Besides, a shorter duration of this technique attenuates tissue dehydration before ablation[20]. Lastly, prescribing vitamin C and a more prolonged low-dose topical corticosteroid regimen, and instructing the patient to wear standard sunglasses after a refined single-step platform, provides further haze-inhibitory effects[19].


  Conclusion Top


Preoperative visual acuity, refractive error, ablation depth, and residual stroma can induce corneal haze postoperatively, but most of the corneal hazes disappear with time. However, some need surgical interference.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Ang BC, Foo RC, Lim EW, Tan MM, Nah GK, Thean LS, et al. Risk factors for early-onset corneal haze after photorefractive keratectomy in an Asian population: outcomes from the Singapore Armed Forces Corneal Refractive Surgery Programme 2006 to 2013. J Cataract Refract Surg 2016; 42:710–716.  Back to cited text no. 1
    
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Ghirlando A, Gambato C, Midena E. LASEK and photorefractive keratectomy for myopia: clinical and confocal microscopy comparison. J Refract Surg 2007; 23:694–702.  Back to cited text no. 3
    
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Kim W, Shah S, Wilson SE. Differences in keratocyte apoptosis following transepithelial and laser-'scrape photorefractive keratectomy in rabbits. J Refract Surg 1998; 14:526–533.  Back to cited text no. 4
    
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Buzzonetti L, Petrocelli G, Laborante A, Mazzilli E, Gaspari M, Valente P, et al. A new transepithelial phototherapeutic keratectomy mode using the NIDEKCXIII Excimer Laser. J Refract Surg 2009; 25:S122–S124.  Back to cited text no. 5
    
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Mounir A, Mostafa EM, Ammar H, Mohammed OA, Alsmman AH, Farouk MM, et al. Clinical outcomes of transepithelial photorefractive keratectomy versus femtosecond laser-assisted keratomileusis for correction of high myopia in South Egyptian population. Int J Ophthalmol 2020; 13:129–134.  Back to cited text no. 14
    
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20.
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Shojaei A, Ramezanzadeh M, Soleyman-Jahi S, Almasi-Nasrabadi M, Rezazadeh P, Eslani M. Short-time mitomycin-C application during photorefractive keratectomy in patients with low myopia. J Cataract Refract Surg 2013; 39:197–203.  Back to cited text no. 25
    
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29.
Weiss RA, Liaw LH, Berns M, Amoils SP. Scanning electron microscopy comparison of corneal epithelial removal techniques before photorefractive keratectomy. J Cataract Refract Surg 1999; 25:1093–1096.  Back to cited text no. 29
    


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