Bicarbonate-buffered lidocaine-epinephrine-hyaluronidase for eyelid anesthesia. A double-masked, randomized clinical trial was conducted to determine if subcutaneous eyelid injections of a bicarbonate-buffered lidocaine-epinephrine-hyaluronidase mixture were less painful than unbuffered injections. Twenty-one patients received both buffered (pH = 7.4) and unbuffered (pH = 4.6) injections. After each injection, patients recorded pain on a scale of 0, "no pain," to 10, "severe pain." Mean pain score for buffered injections was 2.0 versus 4.1 for unbuffered injections (P = 0.0003). Seventeen (81%) of 21 patients ranked the buffered injection less painful. Use of a bicarbonate-buffered lidocaine-epinephrine-hyaluronidase mixture is effective in making ophthalmic anesthesia less painful. 