We are pleased to hear the interest in our work entitled ‘Direct application of bFGF without edge trimming on human subacute tympanic membrane perforation.’ We thank Dr. Jian Yang for reading our paper in depth; we have gone through the author’s queries in detail.

Firstly, Dr. Jian Yang considered in the above paper that “the closure rate of traumatic tympanic membrane perforations (TMPs) in the FGF-2-treated group was significantly greater than that in the observational group (91.7% vs. 52.9%), the average closure time in the latter group was significantly shorter than that of the former group (9.2 ± 2.9 days [range 6–16 days] vs. 18.1 ± 11.4 days [range 3–65 days]) . Therefore, it is not appropriate to treat subacute TMPs by direct application of FGF-2.” Although traumatic TMPs had a higher closure rate for spontaneous healing, the rates of spontaneous healing for large perforations, penetrating perforations, and blast-induced perforations were much lower, and timely myringoplasty was recommended . Some scholars reported that the spontaneous closure rate of blast-induced perforations was 29–38% after 6–12 months , and sub-total and total perforations almost never healed spontaneously . Thus, for a large or total traumatic perforation of the tympanic membrane, human intervention not only shortened the closure time, it improved the closure rate. Improvement in the closure rate would avoid the need for myringoplasty, which is an invasive surgical procedure with potentially severe side effects. In our work, although the spontaneous healing of subacute TMPs shortened the healing time, it did not increase the closure rate. In contrast, the application of FGF-2 to subacute TMPs can significantly improve the closure rate . In addition, FGF-2 applied to acute large perforations not only shortened the closure time but also improved the closure rate .

Secondly, Dr. Yang stated that “FGF-2 is not readily available (and is expensive); conservative treatment is simple and inexpensive; topical application once or twice per day is inconvenient for patients.” Indeed, FGF-2 eardrops have yet to be approved by the United States Food and Drug Administration, and they aren’t widely used in otology clinics worldwide. However, the safety and efficacy of FGF-2 for TMPs have been verified clinically and experimentally and have gradually begun to be used in clinical studies. In addition, FGF-2 is inexpensive compared to myringoplasty; in China, for example, the drops cost only $3.50. According to Dr. Yang, “it is difficult for patients to self-control FGF-2 doses. Overdoses of FGF-2 cause otorrhea and ear discomfort and increase the risk of middle-ear infection.” In our work, approximately 0.1–0.15 mL (2–3 drops) of the FGF-2 solution was applied to the eardrum along the external auditory canal once daily to keep the eardrum moist. The drops were subsequently applied by the patients at home, as instructed, until complete perforation closure was confirmed by the physician. However, it was the physician who determined whether the self-application of FGF-2 by patients at home was correct and whether purulent otorrhea developed during the 2–3 days following the start of treatment. The eardrop dose was adjusted as required to keep the eardrum moist (i.e., not excessively wet or dry) . Thus, the first and second follow-up exams after the start of treatment were important. On confirmation of an effective dose for maintaining a moist eardrum, the dosage could continue to be applied until perforation closure or the complete disappearance of symptoms. Although overdoses of FGF-2 may introduce the risk of middle ear infection, FGF-2 can overcome the healing damage caused by infection and does not affect the closure rate of TMPs . In addition, infection can aggravate the acute inflammation of the chronic wound and restart the healing process for chronic TMPs . This is beneficial for subacute TMPs that are not able to spontaneously heal.

Thirdly, Dr. Yang proposed using FGF-2 for traumatic TMPs. This is an excellent suggestion; however, a large-scale multicenter clinical study has yet to take place. Our recent study suggested that FGF-2 was used to treat traumatic TMPs of different sizes, causes, and durations. Nevertheless, the effect of FGF-2 on TMPs with residual eardrum calcification and involvement of the umbo or malleus was not good . Therefore, clinicians should select the appropriate treatment based on the perforation size and symptoms.