Abstract
Dear Editor,
T
The author, in this letter, first questions the definition of a chronic perforation. The current clinical and scientific literature defines chronic perforations as lasting more than 2–3 months.3–8 In a previous letter, this author also agrees with this definition and states that most authors consider a patient for surgery after a perforation has been present for 3 months. In this letter, the author then references his own work for a treatment in chronic perforations, yet the actual study describes recruitment of perforations present for 1 month (subacute perforations) and not chronic perforations. We are unsure why the author disagrees with the body of scientific literature, with his own recent opinion, and provides a conflicting definition referencing his own results. 2 We, therefore, reject the author's suggestion that an animal model should persist for 6 months.
The author claims that it is impossible to close chronic perforations using a polymer, yet this has never been tested previously. Attention should be paid to the contents of the polymer that include fibrinogen and chitosan, which have been previously shown to enhance wound healing.9–11 Given knowledge of the polymer's contents and their roles in wound healing, it is possible that the polymer group would have had a small amount of healing.
Tympanosclerosis, as the author correctly highlights, affects the success rate of myringoplasty; however, the proposed treatment is not myringoplasty. Myringoplasty relies on a graft to integrate into the residual tympanic membrane tissue, whereas heparin binding epidermal growth factor-like growth factor (HB-EGF) therapy is based on the theory of activation of keratinocyte proliferation and migration from progenitor cell areas distant from the perforation site. This study, to which the author refers to, did see some cases of tympanosclerosis in some of the chronic perforations; however, this did not influence healing rates. 12
The author introduces another contradictory opinion regarding the healing of traumatic perforations. According to the scientific literature, and the author's own recent published opinion, traumatic tympanic perforations tend to heal spontaneously. 13 It is unsure why, in this letter, the author now claims few traumatic perforations heal spontaneously after 3 months. The opinion that acute perforations do not heal spontaneously in the majority is contradictory to the scientific literature, which shows that treatments may affect the time of healing but not the overall rate of healing.14–17
We are unsure of the relevance of the author's comment that the animal model is not completely equal to the clinical situation. An animal model is never completely equal to the clinical situation. We have demonstrated that the current proposed models resemble the human situation in histology, time, Eustachian tube dysfunction, and with the presence of bacteria. 12 The current proposed models are the best available for testing proposed treatments for chronic tympanic membrane perforation before translation to human clinical trials.
The pathway for efficacy and safety for new treatments is controlled by federal regulatory agencies. The progression from animal work through to various phases of human trials is standard practice. There is already growing evidence of the safety and efficacy of HB-EGF, and this is certainly not, as the author claims, “doubtful and even potentially risky.”12,18,19 All treatments come with an element of risk and it is through these translational experiments that the risk is defined. We support further preclinical work being performed before being made available to patients. Using off label growth factors, without demonstrating safety and nonototoxicity in nonhuman models, in patient populations with wounds that likely would have healed without treatment and without long-term follow–up should be considered “risky.”20–25