[Dr.Vad]

Сергей Александрович, по ссылке за номером 4 есть варианты использованных дозировок в зависимости от % раствора, как понимаю 0.5% раствор наносится реже: 2-3 раза, а 0.1% раствор 5 раз в день был оптимальным по эффекту:

Many clinicians have taken their own approach to dose regimens. Common preparations used are timolol 0.5% drops, timolol 0.25%, or 0.5% gel forming solution (GFS), timolol 0.1% gel, propranolol 1% ointmentdall in varying frequencies from twice daily to 5 times daily and between 1 and 10 drops at each dose (Table 1). Success may be defined differently by each group, but a common theme is either size reduction or growth cessation. Propranolol ointment (1e3%) has varying success rates between 87 and 92%; timolol 0.1% has success of 100% in superficial lesions only; timolol 0.5% solution has a success rate of over 98% in all studies, whereas timolol 0.5% GFS varies between 60% and 100%.
In Chakkittakandiyil and Pope’s multicentre study of 73 patients, timolol 0.1% GFS was compared to timolol 0.5% GFS. By using the visual analogue scale (VAS), they showed that children treated with 0.1% timolol had a mean VAS
improvement of 24+/-
29, whilst those treated with 0.5% timolol had a mean improvement of 48+/-28 (P less 0.01). There was a statistically significant difference in treatment response; however, neither hemangioma size nor onset of treatment was factored into the analysis.6 Oranje published a pilot study of timolol 0.1% gel applied either 3 or 4 times daily and found it to be less effective than timolol 0.5%.32 Semkova found that 0.1% gel 5 times daily was beneficial in all patients, suggesting that increased frequency is key to success with lower concentrations.40 Wang concluded that superficial lesions respond better to 3% propranolol ointment than mixed or deep types.47
We use 3 drops of timolol maleate 0.5% solution applied twice a day. The parent applies a drop to their finger and then rubs the medication directly onto the hemangiomatous tissue. Applied this way the likelihood of medication getting into the eye is reduced. This regime is continued until the lesion has regressed, at which point the frequency is reduced to once a day. Should the lesion remain stable, the medication is stopped altogether.