medwireNews: Researchers have found that among people taking long-term hydroxychloroquine, being older, a woman, having chronic kidney disease (CKD), and taking tamoxifen may increase the risk for retinopathy in addition to hydroxychloroquine dose and duration.
April Jorge (Harvard Medical School, Boston, Massachusetts, USA) and team suggest that “[t]hese factors should influence hydroxychloroquine dosing and monitoring for this complication.”
Risk factors were evaluated among 4677 participants (mean age 52.4 years; 82.9% women) within the Kaiser Permanente Northern California health network who began hydroxychloroquine treatment for rheumatologic or dermatologic conditions and were screened for retinopathy after 5 years of use. Each case of retinopathy was classified as having a parafoveal or pericentral pattern based on the primary site of retinal damage.
The majority of participants were non-Hispanic White (58.1%), followed by Hispanic (17.7%), Asian (13.7%), and Black (10.5%) ethnicities.
The study, spanning from 1997 to 2020, with up to 15 years of follow-up, identified 125 cases of hydroxychloroquine retinopathy. Of these, 102 were classified as parafoveal and 23 as pericentral.
The researchers found that older age at the time of hydroxychloroquine initiation was associated with an increased risk for retinopathy, with patients aged 45–54 years being 2.48-fold more likely to develop the complication than those younger than 45 years old, with cumulative 15-year incidences of 5.20% versus 1.93%. For individuals aged 55–64 years, the risk was 3.82-fold greater, with a 15-year cumulative incidence of 7.62%, and those aged 65 years and older had a 5.68-fold increased risk, with a 15-year incidence of 10.57%.
The researchers suggest that age-related thinning of the retina may “render older individuals more vulnerable to the toxic effects of hydroxychloroquine.”
Women were also at increased risk for hydroxychloroquine-related retinopathy, even after accounting for differences in weight-based dose. Compared with men, women were 3.83 times more likely to develop retinopathy, with respective 15-year incidences of 2.60% versus 6.12%.
The present study corroborated previous findings of an association between CKD and increased incident retinopathy. The 407 patients with CKD stage 3 or greater at baseline, characterized by an estimated glomerular filtration rate below 60 mL/min per 1.73 m², had twice the risk for retinopathy than the remaining patients with normal kidney function, at 15-year incidences of 10.36% versus 4.99%.
“Renal insufficiency likely leads to a patient being effectively exposed to a higher systemic dose of the medication,” the investigators note.
Tamoxifen is also associated with retinopathy, the researchers point out, and although it was only being taken by 17 women at baseline and 18 women at the 5-year checkpoint, they looked at it as a risk factor, and found that the cumulative 15-year incidence for retinopathy in these women was 27.78%, compared with 5.43% for those who were not taking tamoxifen, giving a 3.43-fold increased risk.
They propose that “[t]here may be a synergetic toxic effect with hydroxychloroquine on the retina.”
The dose of hydroxychloroquine used was also a risk factor; doses over 6 mg/kg per day were associated with the highest risk for retinopathy (HR=5.30), followed by doses between 5 and 6 mg/kg per day (HR=3.23).
The team suggests that “rather than considering any particular dose to be a safe threshold […], prescribers should use the lowest hydroxychloroquine dose that provides disease control and be wary of using higher doses for an extended period of time.”
With regard to the pattern of retinopathy, Jorge and colleagues found that older age and being female were more strongly associated with the parafoveal than the pericentral pattern, while the opposite was true for those with CKD. And while race was not associated with an increased risk for retinopathy overall, Asian and Black patients had a higher likelihood of developing pericentral retinopathy than non-Hispanic White patients.
“The pericentral pattern is not considered a more advanced form of hydroxychloroquine retinopathy than the parafoveal pattern, “but it may be identified at a later stage because eye care clinicians may be less familiar with its appearance,” say Jorge et al.
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