Evaluating the Efficacy and Safety of Aflibercept Biosimilar (P041) Compared with Originator Product in Patients with Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To assess the noninferiority of biosimilar aflibercept (P041, CinnaGen) to the originator aflibercept (AFL, Regeneron) in terms of efficacy, safety, and immunogenicity. DESIGN: This was a phase Ш, 52-week, multicenter, randomized, double-masked, and active control trial involving eyes in a 1:1 ratio. SUBJECTS: Patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration randomized into the 2 groups of P041 and AFL. METHODS: Patients received an injection of aflibercept every 4 weeks for 3 doses, followed by administration every 8 weeks up to week 48. MAIN OUTCOME MEASURES: The primary outcome was the noninferiority analysis of eyes maintaining vision at week 52. Secondary outcomes included the changes in visual acuity and retinal thickness, safety evaluation, and immunogenicity during the study. RESULTS: In total, 168 eyes of 168 patients were included. At week 52, the proportion of patients maintaining vision was 94.44% in the P041 group compared with 94.52% in the AFL group. The 95% confidence interval (CI) for the difference of maintaining vision from baseline did not exceed the predefined noninferiority margin of 10% (difference, -0.0008; 95% CI, -0.074 to 0.074; P = 0.98). Secondary outcomes indicated similar results in both arms (all P > 0.05). Safety measured outcomes and immunogenicity were similar between the 2 study groups. CONCLUSIONS: Biosimilar aflibercept was noninferior to AFL in eyes with neovascular age-related macular degeneration. Other efficacy and safety findings also indicated the similarity of 2 products. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

CLOSURE OF IDIOPATHIC FULL-THICKNESS MACULAR HOLE AFTER INTRAVITREAL C3F8 INJECTION WITHOUT VITREOMACULAR TRACTION RELEASE: A CASE REPORT AND REVIEW OF LITERATURE.

BACKGROUND: The purpose of this study was to describe a successful closure of macular hole without release of vitreomacular traction after intravitreal perfluoropropane (C3F8) gas injection. CASE PRESENTATION: A 54-year-old woman was referred to our clinic with the history of declined vision after a period of distorted vision in her right eye. After dilated fundus examination and performing optical coherence tomography, a V-shaped vitreomacular traction complicated by full-thickness macular hole was diagnosed and she underwent pneumatic vitreolysis using intravitreal C3F8 gas injection. After 12 weeks, her visual acuity was significantly improved and fundus examination and optical coherence tomography revealed that the macular hole was completely resolved despite persisted vitreomacular traction. CONCLUSION: Intravitreal gas injection would be a promising option to manage idiopathic macular holes not only by releasing the vitreous traction on the macula but also through some not proven or even unknown mechanisms.

Intravenous plus intravitreal erythropoietin for management of methanol toxicity optic neuropathy: A case report and brief review.

Methanol can inhibit cellular aerobic respiration pathway and causes cell hypoxia specially in optic neurons. Despite using many drugs, methanol-induced optic neuropathy (MION) still has a poor prognosis. Here we present a case of MION which is managed by a combination of intravenous and intravitreal erythropoietin in addition to corticosteroids.

Suprachoroidal injection of triamcinolone acetonide plus intravitreal bevacizumab in diabetic macular edema: a randomized pilot trial.

BACKGROUND: To investigate the efficacy of injecting suprachoroidal triamcinolone acetonide (SCTA) plus intravitreal bevacizumab (IVB) into patients with center-involving diabetic macular edema (CI-DME). METHODS: In this phase 2/3 randomized controlled pilot trial, sixty-six eyes with CI-DME and best-corrected visual acuity (BCVA) of at most 20/50 Snellen chart were randomly assigned into two groups. Monotherapy arm received sham injection plus 3 monthly IVB doses and combination arm received a single dose of SCTA and 3 monthly IVB doses. The mean improvements in BCVA and Central subfield thickness (CST), over the three-month was considered the main efficacy outcomes. RESULTS: The mean BCVA improvements were obtained respectively as - 0.20 ± 0.20 log [minimum angle of resolution (MAR)] (P = 0.004) and 0.37 ± 0.24 log MAR (P < 0.001) in monotherapy and combination arms [between-group analysis (P = 0.014)]. Significant improvements were also observed in CST (P = 0.019) in the combination arm compared to the other. No adverse events (elevated intraocular pressure, cataract) were observed in any of the study arms. CONCLUSION: Significant improvements in BCVA and retinal anatomical outcomes demonstrated the additive effects of SCTA to those of anti-vascular endothelial growth factors with no short-term side effects and this combination appears to be a promising option in the management of patients with CI-DME. TRIAL REGISTRATION: The trial was registered in Iranian Registry of Clinical Trials (IRCT20200314046761N1).

Ultra-Widefield Fundus Fluorescein Angiography Findings in Patients with Fuchs' Uveitis Syndrome.

Background: The aim of this study was to evaluate ultra-widefield (UWF) fundus fluorescein angiography (FFA) findings in patients with Fuchs' uveitis syndrome (FUS). Materials and Methods: This cross-sectional study was conducted in patients with FUS. All the patients underwent a complete ophthalmologic examination, and FFA was carried out with Optos UWF retinal imaging. Standard FFA and image acquisition consisted of early phase (15-45 s) images, and late-phase (5-10 min) images were also obtained for both eyes. Results: Forty eyes from twenty unilateral FUS patients, including 11 females (55%), who had a mean age of 38.50 ± 6.97 years, were enrolled. Eighty-five percent of the FUS eyes had optic disc hyperfluorescence (ODH) in the FFA. A significant relationship was observed between ODH and iris heterochromia (P = 0.004). ODH was seen in all the patients with iris heterochromia (n = 16). Peripheral vascular leakage (PVL), capillary nonperfusion, chorioretinal scar, and vascular sheathing were observed in 3, 3, 2, and 8 of the patients' eyes, respectively. Conclusion: UWF FFA imaging seemed to be mandatory for evaluating the prognosis of the FUS patients, and another investigation may require to be conducted to evaluate the effect of antivascular endothelial growth factor agents for the management of PVL in these patients.

Intima-Media Thickness Measurements of the Common Carotid Artery in Patients with Central Serous Chorioretinopathy: A Case-Control Study.

PURPOSE: To evaluate the intima-media thickness (IMT) of the left and right common carotid arteries (CCA) as an indicator of subclinical atherosclerosis in patients with central serous chorioretinopathy (CSCR). METHODS: This was a case-control study involving patients with CSCR and a matched healthy control group. The mean and difference of the left and right CCA IMT were determined and compared between the two groups using carotid duplex high-resolution B-mode ultrasound equipment. RESULTS: The study enrolled 32 CSCR patients (68.8% female, mean age 38.22 ± 5.42 years) and 32 controls (65.6% female, mean age 39.56 ± 5.33 years). The difference in common carotid IMT between the right and left sides was significantly greater in the CSCR group than in the control group (p < 0.001). Additionally, according to logistic regression analysis, patients with CSCR had a greater chance of having differences in IMT between the two sides when compared to the control group (OR: 1.29, 95% CI: 1.09-1.52). CONCLUSION: Our findings indicated that in the CSCR group, the difference between the right and left sides of CCA IMT was significantly greater than in the control group.

Wavefront-guided photorefractive keratectomy with and without iris registration: comparison of astigmatic correction.

This study aimed to compare the visual outcomes after photorefractive keratectomy (PRK), with and without the iris registration (IR) technology. The retrospective cohort study was performed for wavefront-guided PRK using the Technolas 217z100 excimer laser system in patients with myopic astigmatism (cylinder error - 2 to - 4 diopter [D]). Eyes were divided into IR group (IRPRK) and non-IR group (non-IRPRK). Visual acuity (VA), cylindrical refraction, and the astigmatic vector components using the Alpins method were compared between the two groups preoperatively and 6 months postoperatively. Fifty IRPRK patients (66% female, mean age 30.56 ± 6.31 years) and 50 non-IRPRK (60% female, mean age 29.60 ± 5.63 years) were enrolled. The mean logMAR uncorrected VA improved from 0.89 ± 0.44 to 0.032 ± 0.05 in the IRPRK group (P < 0.001) and from 0.89 ± 0.46 to 0.042 ± 0.06 postoperatively while follow-up in the non-IRPRK group (P < 0.001). No statistically significant differences were observed between the two groups regarding mean uncorrected distance VA (P = 0.4), corrected distance VA (P = 0.5), spherical equivalent (P = 0.16), defocus equivalent (P = 0.18), and absolute cylinder (P = 0.94). More than 90% eyes were within ± 1.00 D of emmetropia in both groups. Moreover, Alpins vector analysis revealed that no significant differences were found in any astigmatic parameters between the two groups (P > 0.05). Wavefront-guided PRK independent of the IR status is effective, safe, and predictable in patients with myopic astigmatism. No statistical significance was observed supporting data for the better outcome of visual acuity and astigmatism correction using IR in comparison with a non-IR system.

Intravitreal Injections of Bevacizumab Plus Methotrexate versus Bevacizumab Alone for the Treatment of Diabetic Macular Edema: A Randomized, Sham-Controlled Trial.

PURPOSE: To evaluate the efficacy of intravitreal bevacizumab (IVB) combined with intravitreal methotrexate (IVM) in the treatment of diabetic macular edema (DME). METHODS: In this prospective, interventional contralateral eye study, patients with bilateral DME were randomly allocated to receive three monthly injections of IVB (1.25 mg/0.05 mL) plus IVM (400 µg; 0.16 cc) or IVB alone. The outcome measure was changes in the best corrected visual acuity (BCVA), central macular thickness (CMT), and central macular volume (CMV). RESULTS: Thirty-six treatment-naive eyes of 18 patients with a mean age of 62.38 ± 6.2 years were included in the study. BCVA logMAR changed from 0.95 ± 0.53 at baseline to 0.75 ± 0.53 in the combination group and from 0.72 ± 0.57 to 0.49 ± 0.50 in the IVB alone group at 1 month after the 3rd injection. BCVA improvement in both groups was not statistically significant compared with the baseline value (P > 0.99). Compared with the baseline values, mean CMT and CMV were reduced in both groups; however, these changes did not reach a significant level. The differences of CMT changes between the groups were not statistically significant at month 1 (P = 0.82), month 2 (P = 0.21), and month 3 (P = 0.10). Furthermore, the differences of CMV changes between the groups were not statistically significant at month 1 (P = 0.76), month 2 (P = 0.82), and month 3 (P = 0.11). CONCLUSIONS: This pilot study demonstrated no significant therapeutic effects for IVB combined with IVM compared to IVB alone in treatment-naive DME patients over a 3-month course.

Combination of Intravitreal Bevacizumab and Topical Dorzolamide versus Intravitreal Bevacizumab Alone for Diabetic Macular Edema: A Randomized Contralateral Clinical Trial.

PURPOSE: To evaluate the efficacy of three intravitreal bevacizumab (IVB) injections versus the same combined with 2% of topical dorzolamide in the treatment of diabetic macular edema (DME). METHODS: In this randomized double-masked clinical trial, 32 eyes of 16 treatment-naive patients with bilateral DME were enrolled. The eyes were randomly assigned to receive three monthly injections of IVB (1.25 mg) plus topical dorzolamide 2% twice daily or IVB (1.25 mg) plus topical artificial tear twice daily. Best-corrected visual acuity (BCVA) was the primary outcome of the study followed by the central macular thickness (CMT) and central macular volume (CMV) as the secondary outcomes. RESULTS: Mean BCVA changes were insignificant in both groups. It changed from 0.21 ± 0.08 logMAR at baseline to 0.23 ± 0.09 (P=0.24) in the combination group and from 0.18 ± 0.09 logMAR to 0.21 ± 0.09 (P=0.11) in the IVB alone group, at 3 months, respectively. Changes in mean CMT and CMV were significant in both groups. However, the difference between the groups was not significant at all the visits. In the study, no major ocular complication or systemic side effects were noted regarding IVB or topical dorzolamide. CONCLUSION: This randomized contralateral clinical trial demonstrated that adjuvant topical dorzolamide with IVB injection had no additional effects on IVB in the treatment of DME over a three-month course. This trial is registered with the Iranian Registry of Clinical Trials under the registration code IRCT20131229015975N5.

Detection of clinically significant prostate cancer with PI-RADS v2 scores, PSA density, and ADC values in regions with and without mpMRI visible lesions

ABSTRACT Purpose To determine if PSAD, PSADtz, and ADC values improve the accuracy of PI-RADS v2 and identify men whose concurrent systematic biopsy detects clinically significant cancer on areas without mpMRI visible lesions. Materials and methods Single reference-center, cross-sectional, retrospective study of consecutive men with suspected or known low to intermediate-risk prostate cancer who underwent 3T mpMRI and TRUS-MRI fusion biopsy from 07/15/2014 to 02/17/2018. Cluster-corrected logistic regression analyses were utilized to predict clinically significant prostate cancer (Gleason score ≥3+4) at targeted mpMRI lesions and on systematic biopsy. Results 538 men (median age=66 years, median PSA=7.0ng/mL) with 780mpMRI lesions were included. Clinically significant disease was diagnosed in 371 men. PI-RADS v2 scores of 3, 4, and 5 were clinically significant cancer in 8.0% (16/201), 22.8% (90/395), and 59.2% (109/184). ADC values, PSAD, and PI-RADS v2 scores were independent predictors of clinically significant cancer in targeted lesions (OR 2.25-8.78; P values <0.05; AUROC 0.84, 95% CI 0.81-0.87). Increases in PSAD were also associated with upgrade on systematic biopsy (OR 2.39-2.48; P values <0.05; AUROC 0.69, 95% CI 0.64-0.73). Conclusions ADC values and PSAD improve characterization of PI-RADS v2 score 4 or 5 lesions. Upgraded on systematic biopsy is slightly more likely with PSAD ≥0.15 and multiple small PI-RADS v2 score 3 or 4 lesions.

Detection of clinically signifi cant prostate cancer with PIRADS v2 scores, PSA density, and ADC values in regions with and without mpMRI visible lesions.

PURPOSE: To determine if PSAD, PSADtz, and ADC values improve the accuracy of PI-RADS v2 and identify men whose concurrent systematic biopsy detects clinically significant cancer on areas without mpMRI visible lesions. MATERIALS AND METHODS: Single reference-center, cross-sectional, retrospective study of consecutive men with suspected or known low to intermediate-risk prostate cancer who underwent 3T mpMRI and TRUS-MRI fusion biopsy from 07/15/2014 to 02/17/2018. Cluster-corrected logistic regression analyses were utilized to predict clinically significant prostate cancer (Gleason score ≥3+4) at targeted mpMRI lesions and on systematic biopsy. RESULTS: 538 men (median age=66 years, median PSA=7.0ng/mL) with 780mpMRI lesions were included. Clinically significant disease was diagnosed in 371 men. PI-RADS v2 scores of 3, 4, and 5 were clinically significant cancer in 8.0% (16/201), 22.8% (90/395), and 59.2% (109/184). ADC values, PSAD, and PI-RADS v2 scores were independent predictors of clinically significant cancer in targeted lesions (OR 2.25-8.78; P values <0.05; AUROC 0.84, 95% CI 0.81-0.87). Increases in PSAD were also associated with upgrade on systematic biopsy (OR 2.39-2.48; P values <0.05; AUROC 0.69, 95% CI 0.64-0.73). CONCLUSIONS: ADC values and PSAD improve characterization of PI-RADS v2 score 4 or 5 lesions. Upgraded on systematic biopsy is slightly more likely with PSAD ≥0.15 and multiple small PI-RADS v2 score 3 or 4 lesions.

Comparison of Sub-Bowman Keratoplasty Laser In situ Keratomileusis Flap Properties between Microkeratome and Femtosecond Laser.

BACKGROUND: Since thin and high-quality flaps produce more satisfactory surgical outcomes, flaps created by mechanical microkeratomes are more economical as compared with femtosecond lasers, and no Iranian study has concentrated laser in situ keratomileusis (LASIK) flap peculiarities between Moria Sub-Bowman keratoplasty (SBK) microkeratomes and LDV femtoseconds, the present study compares and contrasts them. MATERIALS AND METHODS: This cross-sectional study was done on all patients who underwent LASIK surgery 1-month before this study. Thirty eyes were divided into per group. Flaps in the first group and second group were created, respectively, using Moria SBK microkeratome and LDV femtosecond laser. The other stages of LASIK were done equally in both groups. One month after surgery, the thickness of flaps was measured by anterior segment optical coherence tomography in five regions of flaps. Corneal anterior density was calculated and recorded 1-month after surgery using pentacam and by employing optical densitometry in a distance in the limit range of 0-6 mm from cornea center. Densitometry measurements were obtained and expressed in standardized grayscale units (GSUs). RESULTS: Postsurgery densitometry results reveal that anterior densities of cornea in limit range of 0-2 mm in groups of LDV femtosecond laser and Moria microkeratome are 21.35 ± 0.87 GSU and 22.85 ± 1.25 GSU, respectively. Accordingly, these two groups are significantly different in this regard (P < 0.001). Moreover, anterior densities of the cornea in the limit range of 2-6 mm in these groups are 19.66 ± 0.99 GSU and 20.73 ± 1.24 GSU, respectively. Accordingly, these two groups are significantly different in this regard (P = 0.04). There is a lower mean of flap thickness in the case of LDV femtosecond laser. CONCLUSION: Femtosecond laser method is greatly preferred as compared with Moria microkeratome because of greater homogeneity in flap thickness, smaller thickness, and lower density in optical zone.

Comparison of subthreshold diode laser micropulse therapy versus conventional photocoagulation laser therapy as primary treatment of diabetic macular edema.

PURPOSE: The aim of the present study was to investigate the effect of subthreshold diode laser micropulse (SDM) in comparison with conventional laser photocoagulation in the treatment of the diabetic macular edema (DME). METHODS: Sixty-eight eyes from 68 patients with clinically significant DME were divided randomly into two equal groups. In the first group, SDM photocoagulation was employed, while conventional laser photocoagulation was performed on the eyes of the second group. Central macular thickness (CMT), central macular volume (CMV), and best corrected visual acuity (BCVA) were measured before, 2, and 4 months after intervention, and the results were compared. RESULTS: The mean CMT was 357.3 and 354.8 microns before the treatment in Groups 1 and 2, respectively (P = 0.85), and decreased significantly to 344.3 and 349.8 after 4 months, respectively (P = 0.012 and P = 0.049). The changes in the central macular thickness was statistically higher in the first group (P = 0.001). The mean CMV significantly decreased in Group 1 (P = 0.003), but it was similar to pretreatment in Group 2 after 4 months (P = 0.31). The BCVA improved significantly in Group 1 (P < 0.001), but it remained unchanged in Group 2 (P = 0.38). CONCLUSIONS: In this study, SDM was more effective than conventional laser photocoagulation in reducing CMT and CMV and improving visual acuity in patients with DME.

Collagen cross-linking effect on progressive keratoconus in patients younger than 18 years of age: A clinical trial.

BACKGROUND: Keratoconus is a bilateral non-inflammatory corneal disease. Collagen cross-linking (CXL) is a new treatment option for the disease that uses ultraviolet A light irradiation and riboflavin administration. The aim of this study is to evaluate the effect of CXL on corneal topographic and refractive values in patients with keratoconus younger than 18 years of age. MATERIALS AND METHODS: For the clinical trial study, 37 patients (64 eyes) younger than 18 years of age with progressive keratoconus were included. Age, sex, family history of keratoconus, and history of allergic disorders and eye rubbing were recorded. Refractive, topographic, and topometric indices were evaluated before and 12 months after the CXL with 3mW for 30 minutes. RESULTS: Mean age (±SD) of the patients was 15.83 ± 1.53 years; 26 (70.3%) of the 37 patients were male. Fourteen (37.8%) had positive family history of keratoconus, 11 (29.7%) had history of allergic disorders, and 15 (40.5%) had positive history of eye rubbing. Of the refractive values, cylinder value decreased significantly from -4.50 ± 0.29 to -4.11 ± 0.28 (P = 0.001). Also, the logarithm of minimal angle of resolution (logMAR) uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) improved significantly 12 months after CXL (P = 0.012 and 0.001, respectively). Maximum keratometry before and after the operation was 53.82 ± 0.72 and 53.33 ± 0.72, respectively (P = 0.018). Differences for simulated K values, the thinnest cornea pachymetry, keratoconus index (KI), index of highest asymmetry (IHA), and index of highest decentration (IHD) before and 12 months after the CXL were statistically significant (P = 0.015, 0.034, <0.001, 0.017, 0.019, and 0.004, respectively). CONCLUSION: CXL improves the refractory, topographic, and topometric indices in patients with keratoconus younger than 18 years of age.

Safety and Efficacy of Propranolol in Comparison With Combination of Fentanyl and Ketamine as Premedication in Cataract Surgery Under the Topical Anesthesia.

This study evaluated the safety and effects of propranolol as a premedication before cataract surgery and compared them with the usual combination doses of fentanyl and ketamine. Among all reffered patients to Feiz Hospital of Esfahan for cataract surgery, 122 patients between Mar to Sep 2010 were enrolled in this study and randomly allocated into one of the following equal groups: 40 mg propranolol, 2 hours before surgery and combination of 15 mg ketamine and 50 µg fentanyl l. 5 min before surgery. The ability to control of hemodynamic instabilities caused by stress and to gain patients satisfaction was compared between two groups. Also, the efficacy of each premedication to control of hemodynamic changes during surgery were evaluated and compared. No significant differences were seen in the patients satisfaction and controlling of stress induced hemodynamic changes between two groups (P>0.05). However, patients in ketamine + fentanyl group showed more nausea and less pain during and after surgery. Moreover, no significant adverse effects were reported during and after the surgery. Our results demonstrated that propranolol can be used safely as a premedication in cataract surgery in the comparable efficacy to ketamine plus fentanyl premedication.

The comparison of retinal blood flow after scleral buckling surgery with or without encircling procedure.

AIM: We aimed to compare peak systolic velocity of central retinal artery (PSV.CRA) and peak systolic velocity of ophthalmic artery (PSV.OA) between patients with retinal detachment who were treated with segmental scleral bucking and scleral buckling with encircling procedure. MATERIALS AND METHODS: This study was a descriptive-analytic cross sectional study that was performed in Isfahan university referral centers since April 2010 to April 2011. Of the patients who have undergone scleral buckling surgery, 20 patients belonging to two groups were randomly selected to enroll in the study. Study groups were, patients who have undergone segmental scleral buckling and the other group were patients who have undergone scleral buckling with encircling procedure. Patients were invited to perform color Doppler imaging. PSV-RA and PSV-OA were measured and documented in both operated and unoperated eyes. All of the Doppler's performed at least three months after ophthalmic surgery. RESULTS: We found significant decrease in PSV.CRA among patients in both groups. In patients who had undergone scleral buckling with encircling procedure PSV.CRA was 11.03 ± 3.04 (cm/sec) and 14.83 ± 4.80 in operated and unoperated eye respectively (P = 0.03). In other hand, who treated with segmental scleral buckling these parameters were 11.02 ± 2.48 and 14.45 ± 4.69 (P = 0.03). PSV.OA did not change significantly in each method. The difference between mean PSV.CRA and PSV.OA in operated eye between two study groups was not significant. CONCLUSION: PSV.CRA reduced significantly in both surgery methods and PSV.OA changes was not significant. However, the mean PSV.CRA and PSV.OA changes did not show statistically significant difference between surgery methods.

Two-step versus Single Application of Mitomycin-C in Photorefractive Keratectomy for High Myopia.

PURPOSE: To evaluate the long-term outcomes of two-step versus single application of mitomycin-C (MMC) during photorefractive keratectomy (PRK) for high myopia. METHODS: This randomized clinical trial included consecutive patients with high myopia (exceeding 7 D). Patients underwent PRK and were randomized to two methods of MMC 0.02% application as follows: in the single application group, MMC was applied for 45 seconds followed by irrigation; in the two-step group MMC was used identically followed by repeat application for another 15 seconds and corneal surface irrigation. Visual acuity, refractive error, pachymetry, topography, corneal haze and complications were compared between the two groups 18 months after surgery. RESULTS: One hundred and forty patients (70 subjects in either study arm) underwent PRK according to the study protocol. Mean spherical equivalent refractive error was significantly reduced from baseline to -1.16±0.39 D in the single application group and to -1.07±0.39 D in the two-step group. Sixteen (11.5%) versus 8 (5.7%) eyes lost one or more line(s) of best corrected visual acuity in the single application group as compared to the two-step group (P=0.05). Corneal haze was observed in 18 (12.9%) and 8 (5.7%) eyes in the single application versus two-step group, respectively (P=0.04). Grade 3 corneal haze was not observed in the two-step group but occurred in five eyes (3.6%) in the single application group (P=0.03). No eyes developed corneal ectasia during the follow-up period. CONCLUSION: Two-step intraoperative application of MMC 0.02% in highly myopic eyes undergoing PRK can reduce the frequency and severity of haze formation.