Myopia or short-sightedness is an ophthalmic condition that leads to blurred vision at distance, generally described by a refractive error of -0.5 diopter or less and a high myopia of -5.0 diopter or less . The prevalence of myopia is increasing; as high as 50% of the world population would have some degree of myopia in 2050, of which about 5% will have high myopia which is associated with the risk of irreversible vision impairment and blindness due to pathological changes in the retina, choroid, and sclera .
Several behavioral modifications to delay the onset and retard of myopia progression, such as encouraging children to spend time outdoors, and limiting closed-vision activities have been recommended but might not be sufficient nor feasible . Other interventions such as special spectacle or contact lens for myopia progression control also have limited practicality with questionable result in slowing progression of myopia .
As a non-selective muscarinic receptor antagonist, atropine has been used as a medical option for slowing myopia progression among children. Despite limited evidence on the exact mechanism of atropine in myopia control, the most plausible mechanism is that it acts directly or indirectly on the retina or scleral, inhibiting thinning or stretching of the scleral, and thereby eye growth. In 2012, Chia et al demonstrated that atropine 0.01% has comparable myopia control efficacy and minimal side effects compared with atropine at 0.1% and 0.5% . Findings from the Atropine for the Treatment of Myopia studies (ATOM2), the 0.01% atropine eye drop could significantly slow the myopia progression by 50% with no clinically significant side effects . The low-dose atropine was endorsed by the World Health Organization Western Pacific Region Meeting on Myopia .
Several commercial 0.01% atropine eye drops have been approved by the Food and Drug Administration for myopia progression control only in some countries. Hence, in-house preparation by diluting a commercial atropine sulfate eye-drop with sterile water [5–8] or balanced salt solution (normal saline) has been applied [9, 10]. A practical technique is drawing 0.1ml of 1% atropine sulfate eye-drop and injecting it into a 10ml bottle of either commercial artificial tear or balanced salt solution eye-drops. According to the package insert, the original 1% atropine sulfate eye-drop is anticipated to be stable for at least 36 months before opening and only 28 days after opening . The shelf-life is expected to be shorter than one month after opening, which is not practical or economical for clinical practice as well as patient convenience and compliance in the long term.
Alternatively, we anticipated that the atropine sulfate injection commonly used for emergency treatment of bradycardia could also be used for the in-house preparation of the diluted atropine eye-drop for myopia progression control. Similar approach has been accomplished for antifungal (Voriconazole)  and immunosuppressive (Cyclosporine A and Tacrolimus)  sterile-water-based eye-drops. Atropine sulfate injection is readily available in any healthcare facility whereas the injection formulation usually contains no preservatives which are always of concern in the eye-drop formulation . Moreover, the atropine sulfate injection could be measured and manipulated more easily than atropine sulfate eye-drop. Physical properties of the injection drug could be visually assessed before use whereas the opaque bottle of commercial eye-drop does not allow visual inspection.
As several solvent candidates such as sterile water, normal saline, and lubricant might affect the efficacy of the active substance, introduce some biological contamination, or change the chemical property of the final product, this study aims to investigate the physical, chemical, microbiological properties as well as the shelf-life of the 0.01% atropine eye-drop prepared by using the atropine sulfate injection diluted in two different solvents and tested in two temperature conditions.