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Purpose: To evaluate the effect of long-term chloroquine intake on the multifocal electroretinogram (mfERG) in female patients with and without maculopathy., Methods: Retrospective analysis of the mfERGs recorded in three different groups: (1) patients with bilateral maculopathy having taken chloroquine, (2) patients without maculopathy having taken chloroquine, and (3) healthy control subjects (age-matched to group 2) who never took chloroquine. MfERGs of each group were averaged, and the data of each patient group were compared to the control group. The main outcome measures were N1 and P1 characteristics and the ring ratio analysis., Results: In group 1, 11 female subjects (22 eyes) were included, group 2 consisted of nine patients (18 eyes) and group 3 of seven healthy female subjects (14 eyes). Compared with healthy controls, patients in group 1 showed significantly reduced response densities of both N1 and P1 across all ring eccentricities except ring 5. Implicit times were significantly delayed only concerning N1 (ring 4 and the sum response of the left eye of group 1). P1 implicit times showed no significant alterations in either group. Ring ratios of the response densities were significantly higher mainly concerning group 1 (N1: ring 5/ring 2 and ring 5/ring 4 of the right eye; P1: all ring ratios of the right eye and all ratios except ring 5/ring 1 and ring 5/ring 4 of the left eye). The only ring ratio being significantly higher in group 2 was P1 ring 5/ring 1 ratio of the right eye., Conclusions: In the absence of clinically apparent maculopathy, chloroquine intake was not associated with major alterations of the mfERG.

Background: Maculopathy or retinopathy can develop as a side effect of chloroquine intake. Despite recommendations for ophthalmologic screening by the American Academy of Ophthalmology (AAO) severe toxic retinal damage still occurs. This study aims to clarify how maculopathy affects patient quality of life and whether it arises only due to non-compliance with screening guidelines., Methods: Patients suffering from chloroquine maculopathy were questioned about the ophthalmologic examinations that took place under therapy and completed a German version of the 25 item visual function questionnaire (VFQ-25)., Results: A total of ten female patients were included in the analysis. Weighted visual acuity ranged from 0.09 to 0.8. Median composite score of the VFQ-25 was 33.9. All patients were periodically screened for ocular toxicity with a median trimestrial screening frequency but five patients did not receive all recommended methods of examination. There was suspicion of retinal damage in only one patient even without the patient reporting complaints. Median time span between onset of visual complaints and the cessation of the drug was 12 months. All patients with complaints reported a continuing deterioration of vision even after cessation., Conclusions: Chloroquine maculopathy has a major impact on the vision-related health status of affected patients, emphasizing the need for its anticipation. Although patients were screened even more frequently than recommended by the AAO only half were examined properly and nine out of ten patients had a delay in diagnosis and in drug cessation. The continuing deterioration of vision even after termination of intake further contributes to the severity of the disease.

Background/aims: To evaluate risk factors for retinal damage due to the intake of chloroquine and hydroxychloroquine., Methods: In a retrospective chart review, patients receiving or having received one of the drugs were classified as affected by maculopathy or retinopathy, or as not affected on the basis of the documented findings. Uncertain cases were excluded. The risk factors as postulated by the American Academy of Ophthalmology (AAO) and additional factors like diagnosis of underlying disease, total dose, nicotine abuse and the sum of the AAO risk factors were compared between both groups., Results: 51 patients with a history of or ongoing treatment with chloroquine (23 individuals) or hydroxychloroquine (28 individuals) were included. Most of the postulated risk factors were expectedly elevated in the affected group. Significant differences applied to age, duration of intake and the sum of AAO risk factors. Surprisingly, positive smoking history was more frequent in the not affected. The toxic threshold of the daily chloroquine dose was exceeded by most of the patients., Conclusions: Age and the duration of intake are major risk factors. Smoking seems to be negligible. The sum of AAO risk factors can give an estimation of the individual risk profile. Individual and weight-adapted dosing is especially essential for chloroquine.

Background: Irreversible maculopathy and retinopathy are well-known adverse effects of chloroquine and hydroxychloroquine. For this article the literature was screened for relevant risk factors. The results were used for recommendations concerning the extent and frequency of ophthalmological monitoring., Methods: A systematic literature review was undertaken., Results: Very few studies on a high evidence level could be retrieved for this problem. Most of the risk factors have not been addressed sufficiently. A higher dosage per kg body mass, long therapy duration, presence of keratopathy and renal or hepatic dysfunction are probably associated with an increased risk to develop a maculopathy/retinopathy. Additional factors such as age, genetic disposition, additional retinal disease, sunlight exposition and nature plus duration of the underlying disease have not sufficiently been demonstrated. Gender, body mass and even the accumulated dosage do not contribute as risk factors according to current knowledge., Conclusion: Beside patient risk factors, the spectrum of ophthalmological methodology and cost considerations have to be considered when thinking about content and frequency of monitoring for the risk of acquiring a (hydroxy)chloroquine-induced maculopathy or retinopathy. In principle, a baseline examination comprising visual acuity (near and far), 10 degree threshold perimetry, colour vision, slit lamp (cornea) and funduscopy is reasonable. One of the high investment techniques such as multifocal ERG, fundus autofluorescence and high resolution optical coherence tomography should be used depending on the existing equipment and experience but not more often than once a year. In suspicious cases or high risk-patients a flexible approach is mandatory., ((c) Georg Thieme Verlag KG Stuttgart-New York.)

Objective: The critical dose of chloroquine/hydroxychloroquine leading to a maculopathy or generalised retinopathy remains undetermined. In the literature, 100 g is considered the dose at which regular vision checks should be performed. Generally, chloroquine is said to be more toxic than hydroxychloroquine. A young patient presenting with toxic maculopathy after 57 g of hydroxychloroquine and a daily dosage of 2 mg/kg body weight prompted us to retrospectively look at our patients examined in this respect over about 1 year., Methods: The data of patients who were examined because of chloroquine/hydroxychloroquine intake or a respective maculopathy/retinopathy were retrospectively analysed. The time period was January 2005 until March 2006. Retinal damage was defined by fundus changes and alteration of the multifocal electroretinogram (ERG)., Results: Twenty-one patients--18 women and three men--were examined. The mean age was 51 years (range 6-71). Five of the nine chloroquine-treated patients developed a maculopathy, and one of them developed an additional generalised retinopathy. Of the patients treated by hydroxychloroquine, three of 12 suffered from a maculopathy and one from an additional generalised retinopathy. The cumulative doses leading to retinal damage ranged from 170 g to 1650 g for chloroquine and from 57 g to 1190 g for hydroxychloroquine. The highest cumulative doses without leading to signs of retinopathy were 790 g for chloroquine and 1200 g for hydroxychloroquine., Conclusions: There is a high variability of cumulative doses of chloroquine/hydroxychloroquine that lead to a toxic retinopathy. Therefore, early and regular ophthalmologic examinations are recommended. Electrophysiological testing should be performed once a year, corresponding to about 60 g of base with one tablet a day. For electrophysiology, the multifocal ERG has turned out to be the most important test in this regard. However, visual acuity and funduscopy should be performed more frequently.

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