Low hydroxychloroquine blood levels in patients who have had gastric bypass surgery.

Gastric bypass surgery, also called Roux-en-Y gastric bypass (RYGB), can result in the malabsorption of medications, requiring the use of higher than usual doses in order to achieve a therapeutic effect. We describe the results of hydroxychloroquine (HCQ) blood levels in three patients with systemic autoimmune disease taking standard HCQ doses and their associated disease activity levels. This is a retrospective review of all patients who had undergone RYGB and were taking HCQ in a rheumatology community-based practice. Two patients with SLE and one patient with primary Sjogren's syndrome had previously undergone RYGB. All three had subtherapeutic HCQ blood levels and active disease. Increasing their HCQ doses above the recommended 400 mg a day dosing resulted in therapeutic HCQ levels in all three patients and better disease control in two of the three patients. RYGB patients may not absorb HCQ adequately, resulting in subtherapeutic HCQ blood levels and inadequate disease control. Patients who have undergone RYGB and are taking HCQ should have drug levels monitored. RYGB patients may require higher than recommended doses of HCQ in order to achieve better disease control and avoid unneeded additional immunosuppressive agents.

ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition).

The clinical multifocal electroretinogram (mfERG) is an electrophysiological test of local retinal function. With this technique, many local ERG responses are recorded quasi-simultaneously from the cone-driven retina under light-adapted conditions. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV: www.iscev.org ), replaces the ISCEV guidelines for the mfERG published in 2007. Standards for performance of the basic clinical mfERG test with a stimulus array of 61 or 103 hexagons, as well as for reporting the results, are specified.

Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy.

BACKGROUND: The American Academy of Ophthalmology recommendations for screening of chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy were published in 2002, but improved screening tools and new knowledge about the prevalence of toxicity have appeared in the ensuing years. No treatment exists as yet for this disorder, so it is imperative that patients and their physicians be aware of the best practices for minimizing toxic damage. RISK OF TOXICITY: New data have shown that the risk of toxicity increases sharply toward 1% after 5 to 7 years of use, or a cumulative dose of 1000 g, of HCQ. The risk increases further with continued use of the drug. DOSAGE: The prior recommendation emphasized dosing by weight. However, most patients are routinely given 400 mg of HCQ daily (or 250 mg CQ). This dose is now considered acceptable, except for individuals of short stature, for whom the dose should be determined on the basis of ideal body weight to avoid overdosage. SCREENING SCHEDULE: A baseline examination is advised for patients starting these drugs to serve as a reference point and to rule out maculopathy, which might be a contraindication to their use. Annual screening should begin after 5 years (or sooner if there are unusual risk factors). SCREENING TESTS: Newer objective tests, such as multifocal electroretinogram (mfERG), spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF), can be more sensitive than visual fields. It is now recommended that along with 10-2 automated fields, at least one of these procedures be used for routine screening where available. When fields are performed independently, even the most subtle 10-2 field changes should be taken seriously and are an indication for evaluation by objective testing. Because mfERG testing is an objective test that evaluates function, it may be used in place of visual fields. Amsler grid testing is no longer recommended. Fundus examinations are advised for documentation, but visible bull's-eye maculopathy is a late change, and the goal of screening is to recognize toxicity at an earlier stage. COUNSELING: Patients should be aware of the risk of toxicity and the rationale for screening (to detect early changes and minimize visual loss, not necessarily to prevent it). The drugs should be stopped if possible when toxicity is recognized or strongly suspected, but this is a decision to be made in conjunction with patients and their medical physicians.

Using multifocal ERG ring ratios to detect and follow Plaquenil retinal toxicity: a review : Review of mfERG ring ratios in Plaquenil toxicity.

Multifocal ERG ring ratios provide a sensitive and objective method to detect ocular toxicity in patients taking hydroxychloroquine (Plaquenil). In order to measure ring ratios, the average mfERG amplitude was calculated for each of five concentric rings of a 61-hexagon mfERG. The age-corrected amplitude of the central hexagon (R(1)) and the ratios of R(1) to each of the successive rings (R(1)/R(2), R(1)/R(3), etc.) were then computed. Normative values for ring ratios were established from a population of 67 normal controls. In the study population, a ring was considered abnormal if it was above the 99% confidence limits for the normal population. The technique was evaluated on 131 eyes of 62 patients taking Plaquenil for a variety of conditions including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. Patients who had taken Plaquenil for an extended period showed a higher incidence of retinal toxicity, regardless of the condition for which they were taking the drug. Among patients who had taken a cumulative dose of less than 1,250 g, 7 of 67 eyes (10%) showed a characteristic mfERG defect, while in patients with a cumulative dosage of 1,250 g or more, 26 of 64 eyes (41%) showed one of these defects. In at least one patient, the technique was able to detect the early onset of Plaquenil toxicity followed by reversal of the toxic effects after the medication was discontinued. It appears appropriate to recommend that mfERG testing be done on all patients on Plaquenil therapy.

ISCEV guidelines for clinical multifocal electroretinography (2007 edition).

The clinical multifocal electroretinogram (mfERG) is an electrophysiological test of local retinal function. With this technique, many local ERG responses, typically 61 or 103, are recorded from the cone-driven retina under light-adapted conditions. This document specifies guidelines for performance of the test. It also provides detailed guidance on technical and practical issues, as well as on reporting test results. The main objective of the guidelines is to promote consistent quality of mfERG testing and reporting within and among centers. These 2007 guidelines, from the International Society for Clinical Electrophysiology of Vision (ISCEV: http://www.iscev.org ), replace the ISCEV guidelines for the mfERG published in 2003.

Detection of early hydroxychloroquine retinal toxicity enhanced by ring ratio analysis of multifocal electroretinography.

PURPOSE: To assess decreased retinal function associated with high cumulative doses of hydroxychloroquine using multifocal electroretinography (mfERG). DESIGN: Retrospective cross-sectional study. METHODS: Sixty-two patients referred for evaluation of hydroxychloroquine retinal toxicity. Controls were 67 normal eyes of 67 patients referred for a variety of conditions in the other eye. Visual symptoms, duration of treatment, daily hydroxychloroquine dose (milligrams and milligrams per kilogram), cumulative dose, condition for which the drug was taken, visual acuity, retinal examination, visual fields, and mfERG amplitude. The average mfERG amplitude was calculated for five concentric rings. The age-corrected amplitude of the central hexagon (R(1)) and the ratios of R(1) to each of the other rings (e.g., R(1)/R(2), R(1)/R(3)) were compared with limits derived from control eyes. RESULTS: The incidence of characteristic mfERG abnormalities in patients referred for evaluation with cumulative hydroxychloroquine doses of more than 1250 g was nearly 50%. It was 2.8 times that found in patients with cumulative doses less than 1250 g. Significant abnormalities were seen with cumulative doses as low as 400 g. The mfERG abnormality most commonly detected was an increased R(1)/R(2) ratio. Cumulative dose was more predictive of mfERG abnormalities than daily dose (either in milligrams or milligrams per kilogram) or duration of treatment. CONCLUSIONS: Functional testing of the retina with mfERG shows locally decreased retinal function in a large fraction of patients referred for evaluation who have taken high cumulative doses of hydroxychloroquine. A prudent mfERG testing strategy is proposed.

Non-familial occult macular dystrophy.

PURPOSE: To present a series of patients who have poor central vision with normal funduscopic examination, fluorescein angiograms, and full field electroretinograms but significantly reduced multifocal electroretinographic responses most of whom are unaware of a family member similarly affected. METHODS: Patients were evaluated clinically and with the use of visual field testing, fluorescein angiography, full field electroretinography, VERIS Multifocal Electroretinographic testing (MFERG), which along with focal electroretinography is currently the only objective method of detecting these localized retinal dysfunctions, and Optical Coherence Tomography (OCT) where possible. RESULTS: Nine patients (18 eyes) referred for evaluation of undiagnosed poor central vision were found to have abnormal multifocal ERG findings affecting all or part of the central portion of the test field. Funduscopic examination, fluorescein angiography, and full field electroretinography were all normal. These patients each reported a long history of poor vision with little if any clinical progression. There were no family members reported to have the same condition although a few were reported to have poor vision and only one of the patients had a sibling with decreased vision. At the time of their first examination patients ages ranged from 13 to 53. CONCLUSION: Although there is little evidence that the condition observed in these patients is inherited, all reported early onset often in childhood. Previous reports by Miyake and co-workers have described Occult Macular Dystrophy condition as an inherited macular dystrophy characterized by progressive macular dysfunction. In the present series there is little historical evidence of progression or of inheritance. Based on this data, Occult Macular Dystrophy may in fact represent more than one condition with multiple etiologies. Several etiologies are considered.