ABSTRACT
PURPOSE: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment. DESIGN: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895). PARTICIPANTS: One hundred thirty-five patients treated at 6 European centers. METHODS: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes. MAIN OUTCOME MEASURES: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates. RESULTS: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred. CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Subject(s)
Acanthamoeba Keratitis , Benzamidines , Biguanides , Humans , Acanthamoeba Keratitis/diagnosis , Acanthamoeba Keratitis/drug therapy , Orphan Drug Production , Prospective StudiesABSTRACT
Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes which are members of the zinc endopeptidase family. They have the ability to degrade extracellular matrix elements, allowing for the release of binding molecules and cell migration. Although metalloproteinases regulate numerous physiological processes within the cornea, overexpression of metalloproteinase genes and an imbalance between the levels of metalloproteinases and their inhibitors can contribute to the inhibition of repair processes, the development of inflammation and excessive cellular proliferation. The involvement of MMPs in the pathogenesis of dystrophic corneal diseases needs clarification. Our analyses focus on the involvement of individual metalloproteinases in the pathogenesis of recurrent corneal erosions and highlight their impact on the development of corneal epithelial basement membrane dystrophy (EBMD). We hypothesize that abnormalities observed in patients with EBMD may result from the accumulation and activation of metalloproteinases in the basal layers of the corneal epithelium, leading to basement membrane degradation. A barrier formed from degradation materials inhibits the normal migration of epithelial cells to the superficial layers, which contributes to the development of the aforementioned lesions. This hypothesis seems to be lent support by the elevated concentrations of metalloproteinases in the corneal epithelium of these patients found in our previous studies on the relationships between MMPs and recurrent corneal erosions.
ABSTRACT
PURPOSE: The aim of this study was to investigate the influence of artificial tears containing either cationic nanoemulsion (CCN) or sodium hyaluronate artificial tears (SH) on early postoperative healing after modern surface refractive surgery. MATERIALS AND METHODS: In this multicenter, prospective, double-masked, parallel-group (1:1), comparative study, 129 patients (n = 255 eyes) were randomized to receive CCN (n = 128) or SH (n = 127) as an adjuvant treatment after either transepithelial photorefractive keratectomy (transPRK) or Epi-Bowman keratectomy (EBK). The patients' perspectives were gathered using the Ocular Surface Disease Index (OSDI) questionnaire, and uncorrected (UCVA), and corrected (BCVA) visual acuity were assessed before and one week and one month after the procedure. In addition, corneal epithelization and subjective assessment of visual blur and eye irritation on drop instillation were assessed at one week postoperatively. RESULTS: No statistically significant differences were found between two groups in age, spherical equivalent refractive error, UCVA, BCVA or OSDI scores before the procedure. There was also no difference between groups in UCVA one week and one month after the procedure. However, statistically significantly lower OSDI scores were found one week and one month after the procedure in the CCN group. Moreover, blurred vision after use of the eye drops was observed less frequently in the CCN group than in the SH group. CONCLUSIONS: The CCN and SH groups had similar postoperative UCVA. However the significantly lower OSDI scores and less frequently blurred vision after application of the eye drops in the CCN group suggest better subjective outcomes in this group.
ABSTRACT
Purpose: To assess the role of selected matrix metalloproteinases in defective corneal re-epithelization in patients with recurrent corneal erosions. Subjects: The study group (group 1) included patients with recurrent corneal erosions qualified for phototherapeutic keratectomy. The group 1 was divided into two subgroups regarding the etiology of recurrent corneal erosions: group 1A, Cogan's basement membrane dystrophy, and group 1B, trauma. The control group (group 2) included patients with healthy eyes qualified for Epi-Bowman Keratectomy. Methods: The analyzed material was the corneal epithelium collected during phototherapeutic keratectomy or Epi-Bowman Keratectomy in the study or control group, respectively. Matrix metalloproteinases concentration was determined by an immunohistochemical method using Human Magnetic Luminex® Assay. Results: The study revealed a statistically significantly higher concentration of matrix metalloproteinase-2 in group 1 compared to the control and a statistically significantly higher concentration of matrix metalloproteinase-3 in group 1 compared to the control. Conclusions: The results obtained in the study can prove that matrix metalloproteinase-2 and matrix metalloproteinase-3 having the ability to dissolve anchoring fibers and the corneal epithelial basement membrane could be responsible for epithelial instability and their accumulation in the corneal epithelium may induce recurrence of erosion.
