Risk factors affecting human traumatic tympanic membrane perforation regeneration therapy using fibroblast growth factor-2

Abstract

Objective: The use of growth factors to achieve closure of human traumatic tympanic membrane perforations (TMPs) has recently been demonstrated. However, pretreatment factors affecting healing outcomes have seldom been discussed. The objective of this study was to evaluate pretreatment factors contributing to the success or failure of healing of TMPs using fibroblast growth factor-2 (FGF-2). Design and participants: A retrospective cohort study of 99 patients (43 males, 56 females) with traumatic TMPs who were observed for at least 6 months after FGF-2 treatment between March 2011 and December 2012. Eleven factors considered likely to affect the outcome of perforation closure were evaluated statistically using univariate and multivariate logistic regression analysis. Interventions: Each traumatic TMP was treated by direct application of FGF-2. Main outcome measures: Complete closure versus failure to close. Results: In total, 99 patients were analyzed. The total closure rate was 92/99 (92.9%) at 6 months; the mean closure time was 10.59 ± 6.81 days. The closure rate did not significantly differ between perforations with or without inverted edges (100.0% vs. 91.4%, p = 0.087), among different size groups (p = 0.768), or among different periods of exposure to injury (p = 0.051). However, the closure rate was significantly different between the high- and low-dose FGF-2 groups (85.0% vs. 98.3%, p = 0.010) and between perforations where the umbo or malleus was or was not involved in perforation (85.4% vs. 98.3%, p = 0.012). Additionally, univariate logistic regression analysis tests showed that it was difficult to achieve healing of these perforations with a history of chronic otitis media or residual TM calcification (p = 0.006), the umbo or malleus was involved in perforation (p = 0.038), and with a high dose of FGF-2 (p = 0.035) compared with control groups. Multivariate logistic regression analysis showed that only a history of chronic otitis media and residual TM calcification and perforation close to the umbo or malleus were associated with non-healing of the TM perforation (p = 0.03 and p = 0.017, respectively) with relative risk factors. Conclusions: Direct application of FGF-2 can be used in all traumatic TMPs, the size of the perforation and inverted edges did not affect the closure rate, and the most beneficial dose was sufficient to keep the residual eardrum environment moist, but without adding liquid. Additionally, multivariate logistic regression analysis revealed that a large perforation was not a major risk factor for nonhealing of TM perforations. However, a history of chronic otitis media, residual TM calcification and involvement of the umbo or malleus in perforation were significant risk factors.