Plaquenil Retinotoxicity Updated Guidelines

Written by Larry J Alexander OD FAAO Thursday, 13 December 2012

The latest guidelines on monitoring a patient on plaquenil plus a few cases.


CASE

  • 54 YEAR OLD
  • ROUTINE EYE EXAM
  • C/O DRY GRITTY EYES
  • HX SLE AND MEDS INCLUDE: ALEVE, PREMARIN, PROTEINEX, AND PLAQUENIL
  • BCVA 20/20 OU

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Re-Evaluation

  • ROUTINE EYE EXAM NOW DEMONSTRATING RETINAL COMPROMISE
  • DRY GRITTY EYES
  • MEDS INCLUDE: ALEVE, PREMARIN, PROTEINEX, AND PLAQUENIL 200 MG QD X 14 YEARS- CUMULATIVE DOSE 1,022,000 MG
  • BCVA 20/20 OU
  • TOTALLY DIFFERENT APPROACH TO PATIENT MANAGEMENT

 What is Plaquenil?

  • HYDROXYCHLOROQUINE AND CHLOROQUINE
  • USED IN U.S. FOR INFLAMMATORY DISORDERS
  • QUINOLONE FAMILY OF DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS – DMARD
  • BELONGS IN THE FAMILY OF ANTIPROTOZOALS
  • RAMP UP TIME OF 3 TO 6 MONTHS
  • LONG ½ LIFE-TAKES A LONG TIME TO GO AWAY

Risk of Toxicity

  • DOSAGE IS SUPPOSED TO BE BASED ON IDEAL WEIGHT
    • WOMEN 100 LBS FOR 5 FT AND 5 LBS FOR EACH EXTRA INCH OF HEIGHT – 5 ‘ 2 ‘’ SHOULD BE 110 LBS
    • MEN ADD 10 LBS -  5 ‘ 8 ‘’ SHOULD BE 150 LBS
    • 6.5 MG/KG/DAY
  • CUMULATIVE DOSE IS THE TRIGGER FOR TOXICITY
    • 1000 GRAMS THE TIPPING POINT
  • REPORTED IN PAST AS 1 % AFTER 5 TO 7 YEARS OF USE
  • 120 LB WOMAN AT 355 MG/DAY FOR 7.7 YEARS TO GET 1,000,000 MG
  • RISK WITH PRE-EXISTING RETINAL CONDITION
  • INCREASED RISK WITH PRE-EXISTING RENAL AND LIVER DISEASE-IF IT CANNOT BE CLEARED IT WILL ACCUMULATE AT LOWER DOSES

Genesis of Retinal Toxicity

  • DRUG BINDS TO AND CONCENTRATES IN MELANIN
  • AFFECTS PERIFOVEAL CELLS..1-1.5 MM RADIUS.. FIRST DISRUPTING RPE FUNCTION
  • THEN DEGRADES CONE PHOTORECEPTORS
  • GANGLION CELL LAYER FIRST AFFECTED FOLLOWED BY OUTER RETINA DAMAGE THEN THE BULL’S EYE

Clinical Signs

  • CORNEAL KERATOPATHY POSSIBLE
  • GCC THINNING
  • OUTER RETINA THINNING-LOSS OF PIL
  • MULTIFOCAL ERG EFFECTED
  • FUNCTIONAL LOSS
  • RPE LOSS AN PERIFOVEAL BULL’S EYE

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CASE

  • 49 YEAR OLD
  • ROUTINE PLAQUENIL CHECK
  • HX SLE AND REPORTED ASSOCIATED LIVER DYSFUNCTION
  • HX OF DRY EYES
  • MEDS INCLUDE: NAPROXEN, AND PLAQUENIL 200 MG QD X 2 YEARS- CUMULATIVE DOSE 146,000 MG
  • BCVA 20/20 OU

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Step 1

The first step in the process should be the education of the patient regarding the potential issues associated with the medication.  The patient must be engaged in the process and the discussion should be documented in the chart. 

Step 2

The restyled guidelines also mandate an examination prior to the initiation of hydroxychloroquineWhile the primary physician should be aware of the new guidelines a general letter to the local doctors and pharmacists would be appropriate. 

Step 3

Assess the patient and carefully chart document regarding:

  • Question complaints including near vision
  • Obtain a thorough medical history
  • Document the Duration and Dosage of the drug
  • Best corrected visual acuities
  • Biomicroscopic evaluation of corneal epithelium for vortex deposits as a possible harbinger toxicity
  • Careful dilated ocular examination paying attention to pigmentary abnormalities in macula and periphery and retinal vasculature
  • Visual field evaluation with 10-2 or other VF test of equal resolution (2 degrees) with attention to pattern deviation

Step 4

Apply at least one of the following specialized tests or obtain a consult to do so:

  • Spectral Domain OCT assessing inner and outer retinal thickness and inner/outer segment juncture in the perifoveal region
  • Autofluorescence imaging to reveal subtle RPE defects and early photoreceptor damage
  • Multifocal Electroretinogram to assess for localized paracentral depression

Marmor MF, Kellner U, Lai TYY, et al. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology 2011;118:415-422.  

WARNING: Note that the following are no longer recommended OR ACCEPTED for early detection of hydroxychloroquine and chloroquine retinotoxicity:

  • Fundus photograph
  • Time Domain OCT
  • Fluorescein angiography
  • Full-field ERG
  • Electro-oculogram
  • Color vision testing
  • Amsler grid
  • 24-2 Visual field testing

Step 5

After establishing baseline screening for toxicity on an annual basis should be continued no later than 5 years after starting the medication BUT CAUTION MUST BE EXERCISED REGARDING CO-EXISTENT RENAL/LIVER DYSFUNCTION WHICH WOULD ALLOW DEVELOPMENT AT A LOWER CUMMULATIVE DOSAGE.   

 Step 5  is a minimal recommendation and it would likewise be judicious to communicate all findings and recommendations in writing to the primary care physician with a copy to the dispensing pharmacist.

These new guidelines have strong medico-legal implications and should be addressed with or without immediate insurance reimbursements. (ABN)

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About the Author(s)

Larry J Alexander OD FAAO

Larry J Alexander OD FAAO

Dr. Alexander (1948-2016) was a 1971 graduate of Indiana University School of Optometry. He served in the US Navy then served as a Professor at the University of Alabama Birmingham School of Optometry. Larry contributed to a number of chapters in textbooks and has published three editions of Primary Care of the Posterior Segment, as well as contributed to the professional literature. He also lectured extensively in the area of ocular and systemic disease. His areas of special interest included dysfunctional tear syndrome, glaucoma and macular degeneration.  His lessons are the basis for this site and he will be dearly missed. 

Comments (3)

  • Paula Koch

    04 February 2013 at 22:04 | #

    great detail - thank you!

    reply

  • Ituah Imafidon

    25 March 2013 at 09:15 | #

    Thank you so much, learning a lot. Thank you sir.

    reply

  • Dan Gauerke

    04 September 2013 at 16:01 | #

    Excellent update. thank you

    reply

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