**Conflict of interest**

No conflict of interest.

### **Notes**

*Adenosine Triphosphate in Health and Disease*

**3.3 Safety evaluations**

discontinuation.

**4. Discussions**

or no concentration feeling).

*3.2.2 Comparison about the background factors*

There was no difference among groups regarding the background factors about gender, age, whether or not other eye diseases, and whether or not of using eye drop for asthenopia (**Table 3**). The larger of initial scores improve larger effect in any symptoms.

Among 33 all subjects, 3 subjects had side effect. 1 subject feel nausea and 2 had diarrhea. There was no relation between subjects with side effect and internal dose per body weight or other background factors. And all subjects improved by oral

In this study, regardless the causes, asthenopia symptoms improved with ingestion of ATP-2Na. And the systemic symptoms (headache, stiff shoulder, fatigue) caused by asthenopia improved, as well as the mental symptoms (depressed feeling

Asthenopia symptoms from extremely strong eye fatigue cannot improve with rest. In report by Suzumura, the cause of asthenopia was categorized into three factors (external environmental factors, ophthalmologic factors, and internal /mental factors), and asthenopia symptoms got worse by collapse of balance between these three factors [9]. In this study, subjects were enrolled by symptoms. We did not research a cause of asthenopia symptoms. Ninety-two percent of subjects had systemic symptoms or mental symptoms. It is possible that the balance of several factors collapsed in enrolled subjects in this study. The more severe the symptoms before ingestion, the stronger the improvement effect was confirmed. Severe symptoms that caused a vicious circle related by various systemic/mental symptoms, possibly improved better than weak symptoms. ATP-2Na increases the blood flow in vertebrae and common carotid artery. For the reason, it is suggested that increased blood flow in ciliary body muscle stabilized accommodation, and increased blood flow in vertebrae improved symptoms such as stiff shoulder. In our study, asthenopia symptoms of subjects who were administered nerve stimulants such as Vitamin B12 improved. Then it is clear that ATP-2Na exerts the

effect depending on the mechanism different from Vitamin preparations.

tive for asthenopia symptoms from each mechanism.

Several studies reported that improvement of accommodation by ATP-2Na was confirmed by examination such as near point meter or accommodo-polyrecorder [5–7]. In these studies, enrolled patients were 20~50 years old whose accommodation was not lost. But from our study ATP-2Na is effective for asthenopia in patients over 65 years old as same as in patients under 65 years old. However, ATP-2Na was not effective for blurred vision symptom. It is suggested that blurred vision symptom related several factors for example accommodative dysfunction or cataract. It is difficult to detect the abnormality in accommodation by traditional examination because of presbyopia. Kajita et al. reported that change of pupil diameter could detect ciliary muscle abnormality as objective findings of asthenopia [10]. It is thought that asthenopia of senior patients is possibly related to imbalance in ciliary muscle [11]. Asthenopia in younger subjects is possibly related to accommodative convulsion, on the other hands, asthenopia in older subjects is possibly related to accommodative semi-dysfunction [12]. Blood flow increase by ATP-2Na was effec-

Among 33 all subjects, 3 subjects had side effect (nausea for 1 and diarrhea for 2). All subjects improved from side effect by discontinuation of ingestion. In

**70**

Reprinted from Japanese Journal of Clinical Ophthalmology 71, 741–747.
