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Unfortunately, the numbers of these diseases were too small to statistically compare the data. Abbreviations: CQ, chloroquine; RW, real weight; min, minimum; max, maximum. The specific details of these patients are shown in Table 3. The risk factors are shown in Table 4.

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Other underlying diseases such as thyroid disease, bulimia nervosa, anemia, hepatitis, rheumatic heart disease, and ischemic stroke were also noted in patients in the retinopathy-negative group. In contrast to CQ, no statistically significant hazard ratios of any items studied in the HCQ group were found. The incidence of CQ and HCQ retinopathy versus duration of medication use were analyzed via Kaplan—Meier survival analysis and are illustrated in Figures 1 and 2.

It is noted that CQ retinopathy can occur as early as 4 months after drug use. Figure 1 Kaplan—Meier survival analysis of patients with CQ retinopathy. Note: Y -axis represents patients who had not developed retinopathy and X -axis represents duration of CQ use. Abbreviation: CQ, chloroquine. Note: Y -axis represents patients who had not developed retinopathy and X -axis represents duration of HCQ use. Abbreviation: HCQ, hydroxychloroquine.

According to results of this study, the incidence of CQ retinopathy was 8. This presentation indicated disease in the full-blown stage. As a result, the studies conducted on the disease yielded quite a very low prevalence of disease, 1 in According to the report of life expectancy in rheumatologic patients by Mok et al 13 and understanding that the normal Thai population has an average life expectancy of However, Puavilai et al and Leecharoen et al reported no relationship between old age and CQ retinopathy.

Table 2 also shows that real body weight was one of the statistically significant risk factors for CQ retinopathy.

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However, the size of the difference was too small to indicate clinical significance. Regardless of the effect of dose per unit of body weight, no previous studies mentioned the relationship between body weight and occurrence of CQ retinopathy. This study found no relationship between duration of CQ use and CQ retinopathy, whereas the revised recommendations of AAO concluded the opposite and recommended screening tests starting not earlier than 5 years of CQ use.

Moreover, those patients in the CQ retinopathy-positive group developed the disease at a median time of days 1.

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  5. Similar results were reported by Chiowchanwisawakit et al, Leecharoen et al, and Puavilai et al. Surprisingly, the Kaplan—Meier analysis of CQ presented in Figure 1 revealed that CQ retinopathy mostly developed within the first 3 years after the patients started the medication and that no retinopathy was detected after 6 years.

    These results were in contrast to the AAO recommendations. Despite the fact that the present study showed a statistically significant relationship between the occurrence of CQ retinopathy and cumulative dose, the results were too small to be clinically significant.

    In addition, the cumulative dose these patients with CQ retinopathy received, This is the reason no significant differences of daily doses in retinopathy in the retinopathy-negative group were found. This could be the reason CQ retinopathy in the Thai patients developed earlier and with a less cumulative dose than the previous studies conducted in Caucasian populations.

    There is currently no conclusive mechanism known for CQ retinopathy. The role of RPE and CQ binding to melanin pigment is still unclear and should be further investigated. According to the results of the present study, the incidence of HCQ retinopathy was 3. None of the risk factors showed statistical significance in the present study, as opposed to the revised AAO recommendations.

    A large prospective study, however, has shown consistent results with the current study of no significant risk factors. The participants diagnosed with HCQ retinopathy were 36 and 39 years old median As compared to the revised AAO recommendations, retinopathy developed at a younger age. Wolfe and Marmor, 16 in a recent, large prospective study, showed no relation between aging and HCQ retinopathy. It was mainly noted that there was no retinopathy found after 3 years. These 2 patients received the drug cumulatively from 80 to g median It can actually be seen that the there is a possible difference between the duration and daily dose of HCQ retinopathy and the retinopathy-negative patients, but the statistics fail to show the significance because of the small number of participants.

    For the same reasons as with the CQ group, the daily dosages of not only patients who were retinopathy positive, but also those who were retinopathy negative tended to be approximately equal to the available dose of the HCQ tablet — mg. Nevertheless, unlike the CQ group, the daily dose per real body weight of the patients who were HCQ retinopathy positive was only 1. In this case, the lower body weight would not be a reasonable explanation for the patients developing retinopathy with less treatment duration and less cumulative dosages compared to Caucasians.

    Chloroquine, Past and Present

    The theory of correlation between HCQ binding to melanin pigment in RPE and its toxicity could be a possible explanation; hence, further studies on pathophysiology of the disease should be done in the future in order to understand these findings. Surprisingly, many results that diverged from the AAO recommendations were found, highlighting the risk factors. These results could lead to further investigation and renewed guidelines for Asian people in the future.

    An obvious limitation of the study was that we used possible toxicity for diagnosis of CQ and HCQ retinopathy. These early findings may be nonspecific and misinterpreted. However, we improved the accuracy of diagnosis by using a combination of 3 diagnostic procedures and demonstrated both functional HVF and structural OCT changes.

    Another limitation was that this study was a retrospective study; also, the number of patients was too small in the HCQ group. It is recommended that further prospective studies on the same issue with larger sample sizes be pursued. There was a statistically significant relationship between age, real body weight, and cumulative dose in patients with retinopathy.

    It was found that the retinopathy could develop before 5 years and with a lower cumulative dose than g.

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    The daily dose exceeding 2. The incidence of HCQ retinopathy was 3. The study found no statistically significant relation between age, real body weight, duration of HCQ use, cumulative dose, and daily dose. A lack of sufficient patients in the study may have failed to prove the significance of risk factors. Since CQ and HCQ are essential drugs to control the effects of connective tissue diseases and the patients sometime need higher doses to control the diseases, it is suggested that patients taking long-term CQ or HCQ should undergo one baseline ophthalmologic screening examination at the first visit and annual screening thereafter.

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    Moreover, the routine mg CQ and mg HCQ tablets should be used cautiously, or divided, especially in patients with low body weight. Browning DJ. Pharmacology of chloroquine and hydroxychloroquine.

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    In: Browning DJ, editor. Hydroxychloroquine and Chloroquine Retinopathy. American Academy of Ophthalmology.

    Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy revision. Chloroquine retinopathy in patients with rheumatoid arthritis. Scand J Rheumatol. Easterbrook M.

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    Long term case of antimalarial toxicity after cessation of treatment. Can J Ophthalmol. Incidence of hydroxychloroquine retinopathy in a large multicenter outpatient practice. Arthritis Rheum. Wolfe F, Marmor MF. Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus.

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    Arthritis Care Res Hoboken. It was this news that caused recent shortages. Other companies have also scaled up their production of this drug, and we anticipate that drug shortages will soon be alleviated. The good news outweighs the bad. If you can, get advance prescriptions now in case the drug does become hard to get later.

    Most patients can miss doses for a few weeks without developing a disease flare, so long as they can restart it again when the drug is available. This was shown in a study published in by a group of Canadian doctors.