Letters
Corresponding Author: Sean T. Neel, MD, MSc, Eye Clinic PC, 668 Skyline Dr, Jackson, TN 38301 ([email protected]). Published Online: January 8, 2015. doi:10.1001/jamaophthalmol.2014.5333. Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Naseri A, McLeod S. Benefits of and barriers to immediate sequential cataract surgery [published online September 18, 2014]. JAMA Ophthalmol. doi:10.1001 /jamaophthalmol.2014.3637. 2. Neel S. A cost and policy analysis comparing immediate sequential cataract surgery and delayed sequential cataract surgery from the physician perspective in the United States [published online September 18, 2014]. JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2014.3335. 3. Ingenito K. Premium cataract surgery goes mainstream: finding opportunity in a slow economy and changing reimbursement climate. Cataract Refract Surg Today. October 2013:51-52. 4. Ellis S. Are you billing for your PC/AC IOL cataract cases correctly? http://www .beckersasc.com/asc-coding-billing-and-collections/are-you-billing-for-your -pcac-iol-cataract-cases-correctly.html. Accessed September 30, 2014.
Prevention of Hydroxychloroquine-Related Retinal Toxic Effects To the Editor We commend Mititelu et al1 on their recent study of hydroxychloroquine toxic effects but take issue with their conclusion. We believe prevention rather than early detection is best practice. Hydroxychloroquine is dosed by lean (“ideal”) body weight, which is based purely on height and sex. It is a hypothetical concept that excludes body fat in determining a person’s weight. Hence, shorter patients will have a lower lean body weight. The default hydroxychloroquine dosage on many electronic prescribing systems and most commonly encountered in practice is 200 mg twice daily. Hydroxychloroquine should be dosed at 6.5 mg/kg lean body weight daily. The default dosage of 200 mg twice daily (400 mg/d) is acceptable for a patient with a lean body weight of more than 61.54 kg (135 lbs; 6.5 mg/kg × 61.54 kg = 400 mg). There are a variety of published formulas for calculating lean body weight, but their difference is marginal.2 Men shorter than 1.63 m (5 ft 4 in) and women shorter than 1.68 m (5 ft 6 in) will have a lean body weight lower than 64.54 kg. Therefore, the default hydrochloroquine dosage of 200 mg twice daily is too high for these patients. In the study by Mititelu and colleagues, all the women with retinal toxic effects were shorter than 1.68 m but had received a dosage of 400 mg/d. We conducted a retrospective record review that was Health Insurance Portability and Accountability Act of 1996 compliant and institutional review board approved.3 We reviewed the electronic medical record of a large, multicenter health maintenance organization for all patients taking hydroxychloroquine in 2009. We identified 675 patients; based on their sex, height, and dosage, it was determined that 370 of 662 females (56%) and 6 of 13 males (46%) were receiving higher than the recommended dosage for their lean body weight. Pautler4 addressed the issue of lean body weight dosing in a letter to the editor in the September 2007 issue of Archives of Ophthalmology. Consistent with our findings, Michaelides et al5 found that 9 of 16 women (56%) were receiving hydroxychloroquine dosages greater than the recommended daily dosage based on lean body weight. 492
With the epidemic of obesity facing us, the best practice for the busy clinician may be to routinely note the height for patients prescribed hydroxychloroquine. We recommend that men shorter than 1.63 m and women shorter than 1.68 m have their daily dosage lowered from the default of 200 mg twice daily (400 mg/d) to prevent retinal toxic effects. Matthew D. Walvick, DO Chau H. Ngo, PharmD Author Affiliations: John Muir Medical Group, Walnut Creek, California (Walvick); Sutter Solano Medical Center, Vallejo, California (Ngo). Corresponding Author: Matthew D. Walvick, DO, John Muir Medical Group, 1450 Treat Blvd, Ste 250B, Walnut Creek, CA 94598 (matthew.walvick_d.o [email protected]). Published Online: January 2, 2015. doi:10.1001/jamaophthalmol.2014.3254. Conflict of Interest Disclosures: None reported. 1. Mititelu M, Wong BJ, Brenner M, Bryar PJ, Jampol LM, Fawzi AA. Progression of hydroxychloroquine toxic effects after drug therapy cessation: new evidence from multimodal imaging. JAMA Ophthalmol. 2013;131(9):1187-1197. 2. Pai MP, Paloucek FP. The origin of the “ideal” body weight equations. Ann Pharmacother. 2000;34(9):1066-1069. 3. Lahey JM, Lehmer JM, Walvick MD, Kolarik E, Lam DH. Incidence and characteristics of Plaquenil toxicity in a large population-based study. Poster presented at: 2008 Annual Meeting of the American Academy of Ophthalmology; November 10, 2008; Atlanta, GA. 4. Pautler SE. Hydroxychloroquine dosages should be calculated using lean body mass. Arch Ophthalmol. 2007;125(9):1303-1304. 5. Michaelides M, Stover NB, Francis PJ, Weleber RG. Retinal toxicity associated with hydroxychloroquine and chloroquine: risk factors, screening, and progression despite cessation of therapy. Arch Ophthalmol. 2011;129(1):30-39.
In Reply We thank Walvick and Ngo for their comments regarding the importance of dosing by ideal body weight in patients using hydroxychloroquine. First, we emphasize that our study was not designed or appropriate to address the question of prevention since we were mainly interested in the course of retinopathy following discontinuation. As alluded to by Walvick and Ngo, in our study we also found that at the time toxic effects were diagnosed, most patients were receiving dosages above the daily recommendations based on their ideal body weight (corrected for their height).1 The question of dosing has been addressed in previous studies, prompting the revised recommendations by the American Academy of Ophthalmology.2 Because the current recommended American Academy of Ophthalmology practice for screening includes a baseline examination, perhaps it is at that point we as ophthalmologists can impact the lives of these patients, paying attention to the question of dosing. Further, as a specialty, we are in need of a concerted effort to create better algorithms for follow-up. For example, with our first patient who developed toxic effects despite receiving a dosage much lower than the recommended dosage, would it have been more appropriate to closely follow a young patient with renal disease from baseline at a more stringent 6-month regimen or should we, in similar situations, recommend against the use of hydroxychloroquine altogether? If we follow such patients more closely, are we going to then face an onslaught of patients who need frequent screening?
JAMA Ophthalmology April 2015 Volume 133, Number 4 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a Florida International University Medical Library User on 06/09/2015
jamaophthalmology.com
Letters
Rheumatologists are very keen on hydroxychloroquine as it is generally safe and effective for many applications. As ophthalmologists and retina specialists, we are perhaps biased against this medication based on the complications we see, which, though rare, can be irreversible and progressive. Although, as Walvick and Ngo noted, appropriate dosing and prevention are important, ophthalmologists need to be aware of the potential long-term toxic effects as shown in our series. Furthermore, certain patients may be more susceptible to this medication at low dosages secondary to underlying genetic, ophthalmic, or medical conditions, similar to patient 1 in our series. In those patients, even careful dosing may not be sufficient to prevent toxic effects. There is a need to alert clinicians (ophthalmologists and rheumatologists) to the dosing issues. Future research may be directed toward designing tools to aid clinicians in planning follow-up for patients, perhaps using a risk calculator. This tool would take into account patient biometric and demographic characteristics as well as systemic risk factors at baseline and stratify patients into categories of risk. Based on this information, this tool would then alert the clinician to dosage errors. Patients deemed to have a higher risk of complications would then be followed up more closely, allowing earlier detection, or perhaps advised against the use of this medication altogether if their risk is deemed too high. Amani A. Fawzi, MD Lee M. Jampol, MD
jamaophthalmology.com
Author Affiliations: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Corresponding Author: Amani A. Fawzi, MD, Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, 645 N Michigan Ave, Ste 440, Chicago, IL 60611 ([email protected]). Published Online: January 2, 2015. doi:10.1001/jamaophthalmol.2014.3257. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Mititelu M, Wong BJ, Brenner M, Bryar PJ, Jampol LM, Fawzi AA. Progression of hydroxychloroquine toxic effects after drug therapy cessation: new evidence from multimodal imaging. JAMA Ophthalmol. 2013;131(9):1187-1197. 2. Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF; American Academy of Ophthalmology. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011;118(2):415-422.
CORRECTION Error in Byline: In the Observation entitled “Paravascular Inner Retinal Defect Associated With High Myopia or Epiretinal Membrane,” published online January 22, 2015, in JAMA Ophthalmology (doi:10.1001/jamaophthalmol.2014.5632), the fifth author’s name should have been given as Abdallah A. Ellabban, and in the Affiliations and Author Contributions as Ellabban. This article was corrected online. Error in Group Information: In the Observation entitled “International Validation of the American Joint Committee on Cancer’s 7th Edition Classification of Uveal Melanoma,” published online January 2, 2015, in JAMA Ophthalmology (doi: 10.1001/jamaophthalmol.2014.5395), the fourteenth author’s name in the AJCC Ophthalmic Oncology Task Force Member Authors section in the Article Information section should have been given as Anibal M. Folgar, MD. This article was corrected online.
(Reprinted) JAMA Ophthalmology April 2015 Volume 133, Number 4
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a Florida International University Medical Library User on 06/09/2015
493
Corresponding Author: Sean T. Neel, MD, MSc, Eye Clinic PC, 668 Skyline Dr, Jackson, TN 38301 ([email protected]). Published Online: January 8, 2015. doi:10.1001/jamaophthalmol.2014.5333. Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Naseri A, McLeod S. Benefits of and barriers to immediate sequential cataract surgery [published online September 18, 2014]. JAMA Ophthalmol. doi:10.1001 /jamaophthalmol.2014.3637. 2. Neel S. A cost and policy analysis comparing immediate sequential cataract surgery and delayed sequential cataract surgery from the physician perspective in the United States [published online September 18, 2014]. JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2014.3335. 3. Ingenito K. Premium cataract surgery goes mainstream: finding opportunity in a slow economy and changing reimbursement climate. Cataract Refract Surg Today. October 2013:51-52. 4. Ellis S. Are you billing for your PC/AC IOL cataract cases correctly? http://www .beckersasc.com/asc-coding-billing-and-collections/are-you-billing-for-your -pcac-iol-cataract-cases-correctly.html. Accessed September 30, 2014.
Prevention of Hydroxychloroquine-Related Retinal Toxic Effects To the Editor We commend Mititelu et al1 on their recent study of hydroxychloroquine toxic effects but take issue with their conclusion. We believe prevention rather than early detection is best practice. Hydroxychloroquine is dosed by lean (“ideal”) body weight, which is based purely on height and sex. It is a hypothetical concept that excludes body fat in determining a person’s weight. Hence, shorter patients will have a lower lean body weight. The default hydroxychloroquine dosage on many electronic prescribing systems and most commonly encountered in practice is 200 mg twice daily. Hydroxychloroquine should be dosed at 6.5 mg/kg lean body weight daily. The default dosage of 200 mg twice daily (400 mg/d) is acceptable for a patient with a lean body weight of more than 61.54 kg (135 lbs; 6.5 mg/kg × 61.54 kg = 400 mg). There are a variety of published formulas for calculating lean body weight, but their difference is marginal.2 Men shorter than 1.63 m (5 ft 4 in) and women shorter than 1.68 m (5 ft 6 in) will have a lean body weight lower than 64.54 kg. Therefore, the default hydrochloroquine dosage of 200 mg twice daily is too high for these patients. In the study by Mititelu and colleagues, all the women with retinal toxic effects were shorter than 1.68 m but had received a dosage of 400 mg/d. We conducted a retrospective record review that was Health Insurance Portability and Accountability Act of 1996 compliant and institutional review board approved.3 We reviewed the electronic medical record of a large, multicenter health maintenance organization for all patients taking hydroxychloroquine in 2009. We identified 675 patients; based on their sex, height, and dosage, it was determined that 370 of 662 females (56%) and 6 of 13 males (46%) were receiving higher than the recommended dosage for their lean body weight. Pautler4 addressed the issue of lean body weight dosing in a letter to the editor in the September 2007 issue of Archives of Ophthalmology. Consistent with our findings, Michaelides et al5 found that 9 of 16 women (56%) were receiving hydroxychloroquine dosages greater than the recommended daily dosage based on lean body weight. 492
With the epidemic of obesity facing us, the best practice for the busy clinician may be to routinely note the height for patients prescribed hydroxychloroquine. We recommend that men shorter than 1.63 m and women shorter than 1.68 m have their daily dosage lowered from the default of 200 mg twice daily (400 mg/d) to prevent retinal toxic effects. Matthew D. Walvick, DO Chau H. Ngo, PharmD Author Affiliations: John Muir Medical Group, Walnut Creek, California (Walvick); Sutter Solano Medical Center, Vallejo, California (Ngo). Corresponding Author: Matthew D. Walvick, DO, John Muir Medical Group, 1450 Treat Blvd, Ste 250B, Walnut Creek, CA 94598 (matthew.walvick_d.o [email protected]). Published Online: January 2, 2015. doi:10.1001/jamaophthalmol.2014.3254. Conflict of Interest Disclosures: None reported. 1. Mititelu M, Wong BJ, Brenner M, Bryar PJ, Jampol LM, Fawzi AA. Progression of hydroxychloroquine toxic effects after drug therapy cessation: new evidence from multimodal imaging. JAMA Ophthalmol. 2013;131(9):1187-1197. 2. Pai MP, Paloucek FP. The origin of the “ideal” body weight equations. Ann Pharmacother. 2000;34(9):1066-1069. 3. Lahey JM, Lehmer JM, Walvick MD, Kolarik E, Lam DH. Incidence and characteristics of Plaquenil toxicity in a large population-based study. Poster presented at: 2008 Annual Meeting of the American Academy of Ophthalmology; November 10, 2008; Atlanta, GA. 4. Pautler SE. Hydroxychloroquine dosages should be calculated using lean body mass. Arch Ophthalmol. 2007;125(9):1303-1304. 5. Michaelides M, Stover NB, Francis PJ, Weleber RG. Retinal toxicity associated with hydroxychloroquine and chloroquine: risk factors, screening, and progression despite cessation of therapy. Arch Ophthalmol. 2011;129(1):30-39.
In Reply We thank Walvick and Ngo for their comments regarding the importance of dosing by ideal body weight in patients using hydroxychloroquine. First, we emphasize that our study was not designed or appropriate to address the question of prevention since we were mainly interested in the course of retinopathy following discontinuation. As alluded to by Walvick and Ngo, in our study we also found that at the time toxic effects were diagnosed, most patients were receiving dosages above the daily recommendations based on their ideal body weight (corrected for their height).1 The question of dosing has been addressed in previous studies, prompting the revised recommendations by the American Academy of Ophthalmology.2 Because the current recommended American Academy of Ophthalmology practice for screening includes a baseline examination, perhaps it is at that point we as ophthalmologists can impact the lives of these patients, paying attention to the question of dosing. Further, as a specialty, we are in need of a concerted effort to create better algorithms for follow-up. For example, with our first patient who developed toxic effects despite receiving a dosage much lower than the recommended dosage, would it have been more appropriate to closely follow a young patient with renal disease from baseline at a more stringent 6-month regimen or should we, in similar situations, recommend against the use of hydroxychloroquine altogether? If we follow such patients more closely, are we going to then face an onslaught of patients who need frequent screening?
JAMA Ophthalmology April 2015 Volume 133, Number 4 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a Florida International University Medical Library User on 06/09/2015
jamaophthalmology.com
Letters
Rheumatologists are very keen on hydroxychloroquine as it is generally safe and effective for many applications. As ophthalmologists and retina specialists, we are perhaps biased against this medication based on the complications we see, which, though rare, can be irreversible and progressive. Although, as Walvick and Ngo noted, appropriate dosing and prevention are important, ophthalmologists need to be aware of the potential long-term toxic effects as shown in our series. Furthermore, certain patients may be more susceptible to this medication at low dosages secondary to underlying genetic, ophthalmic, or medical conditions, similar to patient 1 in our series. In those patients, even careful dosing may not be sufficient to prevent toxic effects. There is a need to alert clinicians (ophthalmologists and rheumatologists) to the dosing issues. Future research may be directed toward designing tools to aid clinicians in planning follow-up for patients, perhaps using a risk calculator. This tool would take into account patient biometric and demographic characteristics as well as systemic risk factors at baseline and stratify patients into categories of risk. Based on this information, this tool would then alert the clinician to dosage errors. Patients deemed to have a higher risk of complications would then be followed up more closely, allowing earlier detection, or perhaps advised against the use of this medication altogether if their risk is deemed too high. Amani A. Fawzi, MD Lee M. Jampol, MD
jamaophthalmology.com
Author Affiliations: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Corresponding Author: Amani A. Fawzi, MD, Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, 645 N Michigan Ave, Ste 440, Chicago, IL 60611 ([email protected]). Published Online: January 2, 2015. doi:10.1001/jamaophthalmol.2014.3257. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1. Mititelu M, Wong BJ, Brenner M, Bryar PJ, Jampol LM, Fawzi AA. Progression of hydroxychloroquine toxic effects after drug therapy cessation: new evidence from multimodal imaging. JAMA Ophthalmol. 2013;131(9):1187-1197. 2. Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF; American Academy of Ophthalmology. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011;118(2):415-422.
CORRECTION Error in Byline: In the Observation entitled “Paravascular Inner Retinal Defect Associated With High Myopia or Epiretinal Membrane,” published online January 22, 2015, in JAMA Ophthalmology (doi:10.1001/jamaophthalmol.2014.5632), the fifth author’s name should have been given as Abdallah A. Ellabban, and in the Affiliations and Author Contributions as Ellabban. This article was corrected online. Error in Group Information: In the Observation entitled “International Validation of the American Joint Committee on Cancer’s 7th Edition Classification of Uveal Melanoma,” published online January 2, 2015, in JAMA Ophthalmology (doi: 10.1001/jamaophthalmol.2014.5395), the fourteenth author’s name in the AJCC Ophthalmic Oncology Task Force Member Authors section in the Article Information section should have been given as Anibal M. Folgar, MD. This article was corrected online.
(Reprinted) JAMA Ophthalmology April 2015 Volume 133, Number 4
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a Florida International University Medical Library User on 06/09/2015
493
