In an open label, two period cross-over study we compared the ocular tolerability of NODS vs. Isopto-Naturale^R eye drops. Thirty healthy volunteers were asked to rate the application system they were using for ocular discomfort, utilizing a visual analog scale in which 100=no ocular discomfort and 0=severe ocular discomfort. In addition each subject had to answer a questionaire and underwent a full ophthalmic control before, at day 7, at day 14 and at day 21 of the study. Each application form had to be applied to one eye only once a day for 7 days, followed by a washout period of 1 week. The type of application form was then changed and again had to be applied to one eye only for 7 consecutive days, followed by a final ophthalmic examination. The mean irritation score was recorded at day 7 and at day 21 of the study. Volunteers had no history of eye disease, no acute pathology of the eye, no contact lenses, no conditional foreign body of the cornea within the last four weeks prior to the study or within the study, no local therapy, no systemic therapy, no diabetes, no pregnancy. Informed consent was obtained. At day 1 one of the two application forms was given to each volunteer in a randomized order. 29 volunteers finished the protocol (16 male, 13 female); mean age: 26 years (range 20–32 years). The mean irritation score of NODS: 35 (2-81); the mean irritation score of Isopto-Naturale^R: 80.4 (45.5–99). The difference of mean irritation score (NODS vs. Isopto-Naturale^R): 46.7 (3.3–82.1) (p<0.01). the="" results="" of="" the="" study="" indicate="" that="" in="" healthy="" volunteers="" nods="" are="" not="" as="" well="" tolerated="" as="" conventional="" eye="" drops="" when="" compared="" for="" ocular="" discomfort.="" however,="" the="" chance="" of="" applying="" drugs="" without="" preservatives="" and="" the="" possibility="" of="" increasing="" the="" rate="" of="" bioavailability="" from="" the="" new="" route="" (nods)="" as="" well="" as="" the="" proportionally="" reduced="" risk="" to="" the="" patient="" of="" systemic="" side="" effects="" after="" nods="" application="" of="" any="" type="" of="" drugs="" should="" be="" taken="" into="">