Various methods can correct presbyopia, but all require devices or surgeries. Recently, supplements or warming devices to relieve presbyopic symptoms have been developed, but no eye drops have been developed. We screened certain compounds possibly related to lens degeneration and identified pirenoxine, which has been used for cataracts, as a possible new pharmacologic treatment for presbyopia. We first researched the anti-presbyopic activity of pirenoxine in rats. The lens elasticity significantly (p = 0.028) increased with exposure to tobacco smoke for 12 days, and pirenoxine eye drops significantly (p < 0.001) suppressed lens hardening, which causes presbyopia in humans. In a parallel randomized controlled clinical study of the subjects in their fifth decade of life, the objective accommodative amplitude (AA) decreased significantly (p < 0.01) by 0.16 diopter (D) in the control group, and there was no detectable change in the treatment group after a 6-month treatment period, suggesting that pirenoxine eye drops might prevent progression of presbyopia. Subjects in their sixth decade of life, in whom the AA was already nearly 0 D, did not show similar results. Pirenoxine eye drops might be a new and the first pharmacologic treatment for preventing progression of presbyopia.
A report in the journal Inorganic Chemistry showed that in liquid solutions pirenoxine could cause decreased cloudiness of a crystallin solution produced to mimic the environment of the eye. Pirenoxine interacts with selenite or calcium ions that have been proven as factors leading to the formation of lens cataract.
The government-led \"evidence-based guidelines for cataract treatment\" labelled pirenoxine and glutathione eye drops, which have been regarded as the standard care for cataracts in Japan, as lacking evidence of effectiveness, causing great upset among ophthalmologists and professional ophthalmology societies. This study investigated the reasons why such \"scientific evidence of treatment effectiveness\" is not easily accepted by physicians, and thus, why they do not change their clinical practices to reflect such evidence.
We conducted a qualitative study based on grounded theory to explore physicians' awareness of \"scientific evidence\" and evidence-supported treatment in relation to pirenoxine and glutathione eye drops, and to identify current barriers to the implementation of evidence-based policies in clinical practice. Interviews were conducted with 35 ophthalmologists and 3 general practitioners on their prescribing behaviours, perceptions of eye drop effectiveness, attitudes toward the eye drop guideline recommendations, and their perceptions of \"scientific evidence.\"
Although few physicians believed that eye drops are remarkably effective, the majority of participants reported that they prescribed eye drops to patients who asked for them, and that such patients accounted for a considerable proportion of those with cataracts. Physicians seldom attempted to explain to patients the limitations of effectiveness or to encourage them to stop taking the eye drops. Physicians also acknowledged the benefits of prescribing such drugs, which ultimately outweighed any uncertainty of their effectiveness. These benefits included economic incentives and a desire to be appreciated by patients. Changes in clinical practice were considered to bring little benefit to physicians or patients. Government approval, rarity of side effects, and low cost of the drops also encouraged prescription.
Physicians occasionally provide treatment without expecting remarkable therapeutic effectiveness, as exemplified by the use of eye drops. This finding highlights that scientific evidence alone cannot easily change physicians' clinical practices, unless evidence-based practices are accepted by the general public and supported by health policy.
Evidence-based Medicine (EBM) is increasingly attracting worldwide attention in public policy , resulting in the mass production of evidence-based clinical guidelines [2, 3]. The paradigm of EBM was introduced to Japan in the mid-1990s and has quickly gained immense popularity among healthcare professionals. The Japanese government has organized ad hoc groups to develop evidence-based, clinical guidelines targeting 23 high priority diseases. However, recent opinions tend to be critical of EBM, arguing that it has not been adequately integrated into Japanese medical practices . Some evidence-based guidelines have come under attack, including those established for cataract treatment. Released in 2003, the guidelines pointed out that no scientific evidence supports the effectiveness of pirenoxine and glutathione eye drops, which are commonly prescribed to treat the condition. Several newspapers reported that healthcare providers are prescribing ineffective eye drops in order to increase the number of patient consultations. Understandably, this media coverage caused much distress among ophthalmologists and professional ophthalmology societies in Japan .
Although EBM advocates argue that misunderstandings surrounding EBM have created this situation, it is also important to understand the dynamics that govern physicians' acceptance or rejection of evidence-based clinical guidelines. We investigated physicians' attitudes and opinions regarding the Evidence-based Clinical Guidelines for Cataract Treatment, and attempted to identify the reasons why physicians sometimes conduct clinical practices that are not supported by scientific evidence. This study focused on physicians' prescribing behaviours, perceptions of pirenoxine and glutathione eye drop effectiveness, attitudes toward the guideline's recommendations, and attitudes toward \"scientific evidence.\" Pirenoxine and glutathione eye drops are commonly prescribed to an estimated 1.3 million cataract patients in Japan. This study also investigated why the guidelines were so controversial among Japanese ophthalmologists, and whether they have influenced physicians' practices. Such exploration is anticipated to reveal the reasons why evidence-based practice has been difficult to integrate into clinical practices in Japan, as well as in other countries.
We conducted face-to-face, open-ended interviews at participants' clinics using a structured interview guide. Questions related to pirenoxine and glutathione eye drops included: frequency of prescription, perceptions about effectiveness, explanations to patients about their effectiveness, implementation of the related clinical guideline (see Appendix), and how the guidelines influenced their practices. One question related to opinions about the application of the EBM paradigm into health policy. When necessary, we added further questions to elucidate participants' perceptions of EBM.
Physicians reported that, in general, patients anticipated the effectiveness of the eye drops and considered them to be the standard of treatment for cataracts. Physicians estimated prescription frequencies ranging from fewer than two in ten to \"almost all\" patients, many of which demanded such prescriptions. Approximately half of the participants conducted monthly follow-up visits with such patients, while the other half considered three-month intervals to be adequate.
The grounds for perceived \"true effectiveness\" were governmental approval of the drops, medical properties based on physiology, bench research or \"first principles.\" The majority of participants believed that the lack of studies proving the effectiveness of the drops was not neccessarily proof of ineffectiveness. Three reasons were put forward for this position: 1) difficulty assessing the effectiveness of preventative medications using conventional epidemiological methods; 2) psychological benefits, which are not generally measured in clinical epidemiology; and 3) the lack of large clinical trials proving the ineffectiveness of the drugs.
Eight ophthalmologists refuted the effectiveness of such medications outright. However, such statements were primarily based on clinical experience rather than on \"scientific evidence.\" GPs generally had no firm opinion regarding the effectiveness of the drops. Despite that GPs did not think that such medications had remarkable effects, they believed them to be clinically effective since they are widely used by experts and frequently requested by patients.
All but one physician agreed that eye drops are necessary to some patients for psychological comfort. Although some participants considered this effect to be spurious, they still argued that such placebo effects should be validated.
None of the participants adopted a clinical practice in which they refused to prescribe eye drops to patients. Physicians' prescription behaviours were broadly divided into four categories; (1) automatic or active prescription, (2) passive prescription, (3) prescription based on patient delegation, and (4) avoiding prescription.
Seventeen ophthalmologists automatically prescribed the eye drops. Eleven physicians reported passive prescription in response to patients' requests. They did not believe them to be clinically effective, and never recommended them out of their own volition. However, when patients requested these preparations, they prescribed them without discussion. GPs who had no opinion about the effectiveness of the drops also prescribed them automatically when requested. That is their role was merely to write a prescription based on a patient's request, rather than to make a formal prescribing decision. Since patients had already been prescribed the drug by an ophthalmologist, the GPs felt they were not in a position to challenge patients' preferences or beliefs, considering it safer to follow the ophthalmologist's advice. In this respect, GPs' attitudes toward prescription were passive, although their prescription behaviour was automatic.
Six physicians, five of whom practised in teaching hospitals, delegated the prescription decision to patients. These participants tended to vacillate in their opinions of the effectiveness of these drops; they did not observe remarkable clinical effects, but recognised that the preparations contain active ingredients and appreciated their psychological effects. Lacking a definitive opinion on the drugs' effectiveness, these participants preferred to provide information and allow their patients to make the ultimate decision. 59ce067264