FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2302013022> ?p ?o ?g. }

• W2302013022 endingPage "1394" @default.
• W2302013022 startingPage "1386" @default.
• W2302013022 abstract "BackgroundThe American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools.Pattern of RetinopathyAlthough the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage.DoseWe recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight.Risk of ToxicityThe risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year.Major Risk FactorsHigh dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen.Screening ScheduleA baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors.Screening TestsThe primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus.ToxicityRetinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication.CounselingPatients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening. The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools. Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. We recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using ≤2.3 mg/kg real weight. The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year. High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen. A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors. The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus. Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication. Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening. Retinal toxicity from chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) has been recognized for many years. Chloroquine toxicity remains a problem in many parts of the world, but is seen less frequently in the United States where the drug largely has been replaced by HCQ. Hydroxychloroquine is used widely for the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis, and related inflammatory and dermatologic conditions. It is now being considered for new applications in diabetes mellitus, heart disease, and adjunct cancer therapy. Thus, it is important for ophthalmologists and other physicians to understand the prevalence and risk factors for retinopathy. The American Academy of Ophthalmology recommendations for screening that were published in 20111Marmor M.F. Kellner U. Lai T.Y. et al.Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy.Ophthalmology. 2011; 118: 415-422Abstract Full Text Full Text PDF PubMed Scopus (466) Google Scholar are revised in this article to account for new scientific data. The recent publication of a large demographic study has shown that toxicity is not rare among long-term users of the drug, and the risk is highly dependent on the daily dose by weight.2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar These data showed that real weight was better than ideal weight for calculating dose, and lower risk was achieved with doses ≤5 mg/kg real weight. It also has been found that the classic “bull's-eye” distribution of toxicity is infrequent in patients of Asian heritage,3Melles R.B. Marmor M.F. Pericentral retinopathy and racial differences in hydroxychloroquine toxicity.Ophthalmology. 2015; 122: 110-116Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar, 4Lee D.H. Melles R.B. Joe S.G. et al.Pericentral hydroxychloroquine retinopathy in Korean patients.Ophthalmology. 2015; 122: 1252-1256Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar who typically show early damage in a more peripheral pattern. Toxicity is of serious ophthalmologic concern because it is not treatable. Nonetheless, it has been demonstrated that central vision can be preserved if damage is recognized before there are changes in the retinal pigment epithelium (RPE).5Marmor M.F. Hu J. Effect of disease stage on progression of hydroxychloroquine retinopathy.JAMA Ophthalmol. 2014; 132: 1105-1112Crossref PubMed Scopus (107) Google Scholar With proper screening, bull's-eye retinopathy, as classically described with these drugs, no longer should be seen. The goal of screening for retinopathy is not to stop valuable drugs at the first borderline abnormality, but to recognize definitive signs of toxicity at an early enough stage to prevent a loss of visual acuity. Ophthalmologists provide a valuable service not only by screening but also by advising medical colleagues and patients about risk, safe dosing, and appropriate screening procedures. Despite the existence of published guidelines, screening practices often have been inconsistent or deficient.6Browning D.J. Impact of the revised American Academy of Ophthalmology guidelines regarding hydroxychloroquine screening on actual practice.Am J Ophthalmol. 2013; 155: 418-428Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar, 7Nika M. Blachley T.S. Edwards P. et al.Regular examinations for toxic maculopathy in long-term chloroquine or hydroxychloroquine users.JAMA Ophthalmol. 2014; 132: 1199-1208Crossref PubMed Scopus (36) Google Scholar The recommendations in this revision are more concise and practical than the prior version, to encourage wider compliance. The mechanism of CQ and HCQ toxicity is not well understood. High experimental doses have acute effects on the metabolism of retinal cells, but it is not clear how these short-term metabolic effects relate to the slow and chronic damage that characterizes the clinical state of toxicity. Binding to melanin in the RPE may serve to concentrate the agents and contribute to, or prolong, their toxic effects. However, melanin binding also could serve as a mechanism for removing toxic agents from intracellular sites of damage. Inner and outer retina are damaged by CQ exposure in animal studies, but recent work suggests that inner retina is not damaged significantly as human HCQ toxicity develops.8Lee M.G. Kim S.J. Ham D.I. et al.Macular retinal ganglion cell-inner plexiform layer thickness in patients on hydroxychloroquine therapy.Invest Ophthalmol Vis Sci. 2014; 56: 396-402Crossref PubMed Scopus (32) Google Scholar, 9de Sisternes L. Hu J. Rubin D.L. Marmor M.F. Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: inner versus outer retina, parafovea versus peripheral fovea.Invest Ophthalmol Vis Sci. 2015; 56: 3415-3426Crossref PubMed Scopus (71) Google Scholar In clinical practice, the primary damage is to the photoreceptors, and as the outer nuclear layer degenerates, there is secondarily disruption of the RPE.10Marmor M.F. Comparison of screening procedures in hydroxychloroquine toxicity.Arch Ophthalmol. 2012; 130: 461-469Crossref PubMed Scopus (133) Google Scholar No anatomic features of the retina and RPE are known to correlate specifically with the parafoveal or extramacular patterns of damage as CQ and HCQ toxicity develops. The macular localization of the disease suggests that light absorption or possibly cone metabolism may play a role, but that is speculation. The clinical picture of HCQ and CQ toxicity had been characterized classically as a bilateral bull's-eye maculopathy, an appearance caused by a ring of parafoveal RPE depigmentation that spares a foveal island. However, this “textbook” pattern should no longer be seen, because recommended screening tests will detect HCQ toxicity long before RPE damage is visible by imaging or fundus examination. Although most patients of European descent show initial photoreceptor damage in the classic parafoveal distribution (Fig 1), most patients of Asian descent will show initial damage in a more peripheral extramacular distribution near the arcades (Fig 2).3Melles R.B. Marmor M.F. Pericentral retinopathy and racial differences in hydroxychloroquine toxicity.Ophthalmology. 2015; 122: 110-116Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar, 4Lee D.H. Melles R.B. Joe S.G. et al.Pericentral hydroxychloroquine retinopathy in Korean patients.Ophthalmology. 2015; 122: 1252-1256Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar African-Americans and Hispanics in that study3Melles R.B. Marmor M.F. Pericentral retinopathy and racial differences in hydroxychloroquine toxicity.Ophthalmology. 2015; 122: 110-116Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar showed predominately a parafoveal pattern of damage as in European subjects, but possibly a greater tendency toward extramacular involvement. The numbers of patients of other races were too small to draw conclusions.Figure 2Findings in the left eye of a 42-year-old Chinese woman showing extramacular retinopathy. She had used 8 mg/kg hydroxychloroquine (HCQ) for 8 years and 4 mg/kg for another 2 years. Top: 30-2 fields in grey scale and pattern deviation, showing partial ring scotoma outside the parafoveal region; multifocal electroretinogram (mfERG) showing signal weakness most strikingly in an inferotemporal arc of extramacular responses (traces extend to 20° eccentricity). Bottom: Autofluorescence image showing increased autofluorescence near the arcades (left arrow) and decreased autofluorescence that signals early RPE loss more peripherally (right arrow); Spectral-domain optical coherence tomography (SD OCT) cross-section showing marked loss of outer nuclear layer and ellipsoid zone corresponding to the increased autofluorescence (left arrow), and beginning retinal pigment epithelium (RPE) disruption at the outer edge of the scan (right arrow). There is no parafoveal damage. Modified with permission from Melles RB, Marmor MF. Pericentral retinopathy and racial differences in hydroxychloroquine toxicity. Ophthalmology 2015;122:110–6.3Melles R.B. Marmor M.F. Pericentral retinopathy and racial differences in hydroxychloroquine toxicity.Ophthalmology. 2015; 122: 110-116Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar OS = left eye.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Visual acuity usually is excellent with either pattern until severe stages of damage, and most patients who develop HCQ toxicity have no visual symptoms at all. A few perceptive patients may notice paracentral scotomas while reading. If drug exposure continues, the area of functional disturbance expands, the RPE becomes involved, and the maculopathy can encroach on the foveal center with eventual loss of visual acuity (Fig 3).2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar, 10Marmor M.F. Comparison of screening procedures in hydroxychloroquine toxicity.Arch Ophthalmol. 2012; 130: 461-469Crossref PubMed Scopus (133) Google Scholar Cystoid macular edema sometimes may develop,11Kellner S. Weinitz S. Farmand G. Kellner U. Cystoid macular oedema and epiretinal membrane formation during progression of chloroquine retinopathy after drug cessation.Br J Ophthalmol. 2014; 98: 200-206PubMed Google Scholar and advanced cases show widespread RPE and retinal atrophy with loss of visual acuity, peripheral vision, and night vision. Hydroxychloroquine and CQ retinopathy can progress even after the drugs are stopped, although the amount of progression and the risk to vision are functions of the severity of retinopathy at the time it is detected.5Marmor M.F. Hu J. Effect of disease stage on progression of hydroxychloroquine retinopathy.JAMA Ophthalmol. 2014; 132: 1105-1112Crossref PubMed Scopus (107) Google Scholar, 11Kellner S. Weinitz S. Farmand G. Kellner U. Cystoid macular oedema and epiretinal membrane formation during progression of chloroquine retinopathy after drug cessation.Br J Ophthalmol. 2014; 98: 200-206PubMed Google Scholar It seems doubtful that this late progression of damage after stopping the drug results from a continued reservoir of the drug, although clearance from the body does take many months. The late progression may represent a gradual decompensation of cells that were injured metabolically during the period of drug exposure. Chloroquine, and less frequently HCQ, can cause whorl-like intraepithelial deposits (verticillata) in the cornea. These corneal changes are not a direct marker for retinal damage, are not associated with visual loss, and in contrast to retinopathy are usually reversible. Earlier literature on the prevalence of CQ or HCQ retinopathy included few patients on long-term therapy and only recognized severe toxicity (bull's-eye changes). These reports have been superseded now by a large study of 2361 patients who used HCQ for more than 5 years and were evaluated with 10-2 visual fields or spectral-domain optical coherence tomography (SD OCT) so that toxicity could be recognized before there were any visible signs on fundus examination.2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar The overall prevalence of toxicity in this study population was 7.5%, although it varied greatly with the daily dose and duration of use. Daily dose (more properly, daily use, as measured by actual pharmacy dispensing) was the most critical determinant of risk, and the risk was more closely correlated with real weight than ideal weight. Very thin patients in particular are at increased risk when dose is calculated by ideal weight (as previously recommended). Patients in this new study2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar mostly had been prescribed routine doses of HCQ by prior standards, but the average use was approximately 5.0 mg/kg of real weight because of varying compliance and body habitus. Thus, 5.0 mg of HCQ/kg real weight corresponds with present medical prescription practices and should be therapeutically effective for most patients. Population statistics from the new study showed that patients taking HCQ using 4.0 to 5.0 mg/kg real weight had markedly lower cumulative risk of toxicity than those using higher levels. Kaplan–Meier curves show that patients staying with ≤5.0 mg/kg have less than 1% risk in the first 5 years of therapy and less than 2% up to 10 years (Fig 4). Beyond this point, the risk increases sharply to approximately 20% after 20 years. The risk is much higher when the daily dose is higher. Although the risk is smaller with low doses, it is not clear that there is any truly “safe” dosage for long durations of use. Smoothed response curves (Fig 5) show that the annual incremental risk (for a patient who shows no signs of toxicity) is less than 1% during the first 10 years of therapy if use is ≤5.0 mg/kg and increases to only approximately 4% after 20 years. Thus, this dosage recommendation is associated with a relatively acceptable risk of toxicity for patients being screened annually. On the basis of the risk data described, we recommend that all patients using HCQ keep daily dosage <5.0 mg/kg real weight.2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar There may be rare instances when higher doses are needed to manage life-threatening disease or a lower limit is advisable because of major risk factors (described later). Following this guideline will minimize the risk of retinopathy and allow long-term use of HCQ for most patients. Previous recommendations to use ideal body weight for the calculation of dose were based on the idea that these drugs were not retained in fat; however, the available laboratory studies show that these drugs store primarily in melanotic tissue, liver, and kidney, whereas concentrations are low in muscle, fat, and a variety of other organs.12McChesney E.W. Shekosky J.M. Hernandez P.H. Metabolism of chloroquine-3-14C in the rhesus monkey.Biochem Pharm. 1967; 16: 2444-2447Crossref Scopus (25) Google Scholar, 13McChesney E.W. Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate.Am J Med. 1983; 75: 11-18Abstract Full Text PDF PubMed Scopus (209) Google Scholar Ideal weight formulas result in overdosage in thin individuals, whereas the recommended formula using real weight accounts for risk evenly over a broad range of body habitus.2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar There are no comparable demographic data for CQ use and toxicity. The mechanisms of action are presumed to be similar for both drugs, and older clinical literature on antimalarial toxicity approximately equated 3.0 mg of CQ with 6.5 mg of HCQ.14Marmor M.F. Carr R.E. Easterbrook M. et al.Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology.Ophthalmology. 2002; 109: 1377-1382Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar With this estimation, the equivalent of 5.0 mg/kg HCQ would be 2.3 mg/kg CQ. Many reports suggest that CQ is somewhat more toxic than HCQ, but there are no good data on pharmacologic equivalence. The higher toxicity of CQ in clinical use may be an artifact of common prescription practices, which have been biased by the available CQ tablet size (250 mg). Almost any patient taking 1 tablet of CQ will receive more than 2.3 mg/kg. Because HCQ is available in 200 mg tablets and CQ is available in 250 mg tablets, it may seem a challenge to prescribe intermediate doses. However, blood levels of these drugs only stabilize over many weeks, so that variable dosing will average out over time. Intermediate doses can be obtained easily by splitting tablets or by simply eliminating a tablet on certain days of the week. In theory, blood levels would seem an aid to dosing or to the evaluation of poor clearance of these drugs (see “Renal Disease”). However, literature on the measurement of HCQ blood level has shown it to be an unreliable indicator of medical effectiveness or toxicity.15Lee J.Y. Luc S. Greenblatt D.J. et al.Factors associated with blood hydroxychloroquine level in lupus patients: renal function could be important.Lupus. 2013; 22: 541-542Crossref PubMed Scopus (26) Google Scholar, 16Carmichael S.J. Day R.O. Tett S.E. A cross-sectional study of hydroxychloroquine concentrations and effects in people with systemic lupus erythematosus.Intern Med J. 2013; 43: 547-553Crossref PubMed Scopus (15) Google Scholar, 17Costedoat-Chalumeau N. Dunogué B. Leroux G. et al.A critical review of the effects of hydroxychloroquine and chloroquine on the eye.Clin Rev Allergy Immunol. 2015; 49: 317-326Crossref PubMed Scopus (86) Google Scholar Hydroxychloroquine is metabolized by cytochrome P450 enzymes, which can be affected by a variety of drugs, and some of the variability in blood levels may relate to these metabolic pathways.18Jallouli M. Galicier L. Zahr N. et al.Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus.Arthritis Rheumatol. 2015; 67: 2176-2184Crossref Scopus (97) Google Scholar, 19Lee Y. Vinayagamoorthy N. Han K. et al.Association of polymorphisms of cytochrome P450 2D6 with blood hydroxychloroquine levels in patients with systemic lupus erythematosus.Arthritis Rheumatol. 2016; 68: 184-190Crossref Scopus (87) Google Scholar The most important risk factors are listed in Table 1.Table 1Major Risk Factors for Toxic RetinopathyDaily dosage HCQ>5.0 mg/kg real weight CQ>2.3 mg/kg real weightDuration of use>5 Yrs, assuming no other risk factorsRenal diseaseSubnormal glomerular filtration rateConcomitant drugsTamoxifen useMacular diseaseMay affect screening and susceptibility to HCQ/CQCQ = chloroquine; HCQ = hydroxychloroquine. Open table in a new tab CQ = chloroquine; HCQ = hydroxychloroquine. The most critical risk factor for the development of HCQ toxicity is excessive daily dose by weight.2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar Dosage >5.0 mg/kg dramatically increases both population risk and annual incremental risk, and extreme doses can be exceedingly dangerous. Two recent reports on patients receiving HCQ at 800 to 1000 mg/day (up to 20 mg/kg) for nonrheumatoid diseases showed a 25% to 40% incidence of retinopathy and signs of damage within 1 to 2 years.20Leung L.S. Neal J.W. Wakelee H.A. et al.Rapid onset of retinal toxicity from high-dose hydroxychloroquine given for cancer therapy.Am J Ophthalmol. 2015; 160: 799-805Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 21Navajas E.V. Krema H. Hammoudi D.S. et al.Retinal toxicity of high-dose hydroxychloroquine in patients with chronic graft-versus-host disease.Can J Ophthalmol. 2015; 50: 442-450Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar Duration of use is linked to dosage as a critical factor. Even patients using a recommended dose have significant risk after decades of use. Earlier literature had suggested that “cumulative dose” (which combines daily dose and duration) might be a simple indicator of risk,1Marmor M.F. Kellner U. Lai T.Y. et al.Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy.Ophthalmology. 2011; 118: 415-422Abstract Full Text Full Text PDF PubMed Scopus (466) Google Scholar but this does not hold up well.2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar Risk is most accurately assessed on the basis of duration of use relative to daily dose/weight, as charted in Figures 4 and 5. Hydroxychloroquine and CQ are cleared to a large degree by the kidney, so that renal disease effectively increases the circulating level of the drug and the risk of toxicity.2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar, 22Chiang E. Jampol L.M. Fawzi A.A. Retinal toxicity found in a patient with systemic lupus erythematosus prior to 5 years of treatment with hydroxychloroquine.Rheumatology (Oxford). 2014; 53: 2001Crossref PubMed Scopus (13) Google Scholar Renal disease is not uncommon in SLE and related diseases, so that careful inquiry is important. Patients with renal disease can have unpredictably high blood drug levels, and both dosage and screening frequency may need to be adjusted. An unexpected finding of the recent large study on HCQ use was that concomitant tamoxifen (a drug used for long-term treatment of breast cancer) increased the risk of toxicity approximately 5-fold.2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar The reasons are unclear, although tamoxifen is a retinal toxin in its own right, and there may be adverse metabolic synergy. Newer estrogen analogs such as anastrozole have not shown an association with HCQ toxicity to date, but the number of patients studied has been limited. Patients taking tamoxifen need careful dosing and screening. Patients with underlying retinal disease may be at higher risk for toxicity, although there are no specific data to confirm this. It seems reasonable not to add a potentially toxic agent to the retina on top of a retinal dystrophy or significant degeneration. The other major concern with maculopathy is that it may cause test abnormalities that interfere with the interpretation of screening procedures (visual fields, SD OCT, fundus autofluorescence [FAF], multifocal electroretinogram [mfERG]). Thus, significant central photoreceptor loss would be a contraindication, whereas isolated drusen (that leave good visual fields and intact photoreceptor structure) should not interfere with screening. Elderly patients might seem to be at higher risk, given that aged tissue could be less resistant to the toxic effects of a medication. However, the recent demographic study found no significant association between age and risk of toxicity.2Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (392) Google Scholar The liver participates in the metabolism of these agents, but no clear association between liver disease and toxicity has been demonstrated. There have been suggestions that some patients have a genetic predisposition to HCQ toxicity (e.g., from abnormalities in the ABCA4 gene),23Shroyer N.F. Lewis R.A. Lupski J.R. Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy: is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease?.Am J Ophthalmol. 2001; 131: 761-766Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar but a new report suggests that some nonpathogenic ABCA4 polymorphisms actually may be protective.24Grassman F. Bergholz R. Mändl J. Common synonymous variants in ABCA4 are protective for chloroquine induced maculopathy (toxic maculopathy).BMC Ophthalmol. 2015; 15: 18Crossref PubMed Scopus (33) Google Scholar Polymorphisms in the cytochrome P450 gene might influence blood concentration.18Jallouli M. Galicier L. Zahr N. et al.Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus.Arthritis Rheumatol. 2015; 67: 2176-2184Crossref Scopus (97) Google Scholar, 19Lee Y. Vinayagamoorthy N. Han K. et al.Association of polymorphisms of cytochrome P450 2D6 with blood hydroxychloroquine levels in patients with systemic lupus erythematosus.Arthritis Rheumatol. 2016; 68: 184-190Crossref Scopus (87) Google Scholar Genetic factors may underlie the difference in disease presentation between European and Asian eyes. Hydroxychloroquine and CQ retinopathy are not reversible, and cellular damage may progress even after the drugs are stopped. When retinopathy is not recognized until a bull's-eye appears, the disease can progress for years, often with foveal thinning and an eventual loss of visual acuity. However, when retinopathy is recognized early, before RPE damage, there is only mild and limited progression after discontinuing the medication, and the fovea is not threatened.5Marmor M.F. Hu J. Effe" @default.
• W2302013022 created "2016-06-24" @default.
• W2302013022 creator A5019648757 @default.
• W2302013022 creator A5022846317 @default.
• W2302013022 creator A5029106850 @default.
• W2302013022 creator A5074847557 @default.
• W2302013022 creator A5078702547 @default.
• W2302013022 date "2016-06-01" @default.
• W2302013022 modified "2023-10-14" @default.
• W2302013022 title "Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision)" @default.
• W2302013022 cites W1487688532 @default.
• W2302013022 cites W1544997632 @default.
• W2302013022 cites W1552581629 @default.
• W2302013022 cites W1636963895 @default.
• W2302013022 cites W187949669 @default.
• W2302013022 cites W1967202417 @default.
• W2302013022 cites W1985500032 @default.
• W2302013022 cites W1994019668 @default.
• W2302013022 cites W1994344419 @default.
• W2302013022 cites W2003797154 @default.
• W2302013022 cites W2025113750 @default.
• W2302013022 cites W2026206682 @default.
• W2302013022 cites W2037999651 @default.
• W2302013022 cites W2043373786 @default.
• W2302013022 cites W2066077597 @default.
• W2302013022 cites W2069319161 @default.
• W2302013022 cites W2071235764 @default.
• W2302013022 cites W2073491267 @default.
• W2302013022 cites W2092406009 @default.
• W2302013022 cites W2095161148 @default.
• W2302013022 cites W2116072674 @default.
• W2302013022 cites W2138615668 @default.
• W2302013022 cites W2139235296 @default.
• W2302013022 cites W2140071542 @default.
• W2302013022 cites W2146879748 @default.
• W2302013022 cites W2155989231 @default.
• W2302013022 cites W2158319986 @default.
• W2302013022 cites W2184509447 @default.
• W2302013022 cites W2253161284 @default.
• W2302013022 cites W2296942549 @default.
• W2302013022 cites W2331623140 @default.
• W2302013022 doi "https://doi.org/10.1016/j.ophtha.2016.01.058" @default.
• W2302013022 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26992838" @default.
• W2302013022 hasPublicationYear "2016" @default.
• W2302013022 type Work @default.
• W2302013022 sameAs 2302013022 @default.
• W2302013022 citedByCount "773" @default.
• W2302013022 countsByYear W23020130222015 @default.
• W2302013022 countsByYear W23020130222016 @default.
• W2302013022 countsByYear W23020130222017 @default.
• W2302013022 countsByYear W23020130222018 @default.
• W2302013022 countsByYear W23020130222019 @default.
• W2302013022 countsByYear W23020130222020 @default.
• W2302013022 countsByYear W23020130222021 @default.
• W2302013022 countsByYear W23020130222022 @default.
• W2302013022 countsByYear W23020130222023 @default.
• W2302013022 crossrefType "journal-article" @default.
• W2302013022 hasAuthorship W2302013022A5019648757 @default.
• W2302013022 hasAuthorship W2302013022A5022846317 @default.
• W2302013022 hasAuthorship W2302013022A5029106850 @default.
• W2302013022 hasAuthorship W2302013022A5074847557 @default.
• W2302013022 hasAuthorship W2302013022A5078702547 @default.
• W2302013022 hasBestOaLocation W23020130221 @default.
• W2302013022 hasConcept C118487528 @default.
• W2302013022 hasConcept C119767625 @default.
• W2302013022 hasConcept C126322002 @default.
• W2302013022 hasConcept C134018914 @default.
• W2302013022 hasConcept C142724271 @default.
• W2302013022 hasConcept C2777425658 @default.
• W2302013022 hasConcept C2778048844 @default.
• W2302013022 hasConcept C2778313320 @default.
• W2302013022 hasConcept C2779123688 @default.
• W2302013022 hasConcept C2779134260 @default.
• W2302013022 hasConcept C3008058167 @default.
• W2302013022 hasConcept C524204448 @default.
• W2302013022 hasConcept C555293320 @default.
• W2302013022 hasConcept C71924100 @default.
• W2302013022 hasConceptScore W2302013022C118487528 @default.
• W2302013022 hasConceptScore W2302013022C119767625 @default.
• W2302013022 hasConceptScore W2302013022C126322002 @default.
• W2302013022 hasConceptScore W2302013022C134018914 @default.
• W2302013022 hasConceptScore W2302013022C142724271 @default.
• W2302013022 hasConceptScore W2302013022C2777425658 @default.
• W2302013022 hasConceptScore W2302013022C2778048844 @default.
• W2302013022 hasConceptScore W2302013022C2778313320 @default.
• W2302013022 hasConceptScore W2302013022C2779123688 @default.
• W2302013022 hasConceptScore W2302013022C2779134260 @default.
• W2302013022 hasConceptScore W2302013022C3008058167 @default.
• W2302013022 hasConceptScore W2302013022C524204448 @default.
• W2302013022 hasConceptScore W2302013022C555293320 @default.
• W2302013022 hasConceptScore W2302013022C71924100 @default.
• W2302013022 hasIssue "6" @default.
• W2302013022 hasLocation W23020130221 @default.
• W2302013022 hasLocation W23020130222 @default.
• W2302013022 hasOpenAccess W2302013022 @default.
• W2302013022 hasPrimaryLocation W23020130221 @default.
• W2302013022 hasRelatedWork W2005384490 @default.
• W2302013022 hasRelatedWork W2154597616 @default.

• next