This document discusses using multifocal electroretinography (mfERG) to detect early signs of hydroxychloroquine retinal toxicity. Seven patients on hydroxychloroquine for 5+ years with normal exams showed retinal abnormalities on mfERG testing before other screening methods. The authors conclude mfERG may be useful as an early indicator of developing toxicity and should be considered for higher risk patients.

1. Multifocal ERG in
Hydroxychloroquine
Retinopathy
Maria Noel Vacarezza, MD
Peter J Savino, MD
Raed Behbehani, MD
Elizabeth L Affel, MS

2. Hydroxychloroquine Retinal Toxicity
 Infrequent.
 Irreversible.
 Increased by:
– High daily (6.5mg/kg/d)(cumulative(?)) dose.
– Duration of treatment (>5yrs).
– Renal/hepatic disease.
– Obesity.
– Age (>60).
– Concurrent retinal disease.

3. Current Screening Recommendations
(AAO)
 Complete ophthalmologic examination.
 Visual field: Humphrey 10-2 (white)
 Amsler grid.
 Color vision: Ishihara.
 Optional tests:
– Fundus Photography.
– IVFA.
– Electrophysiologic studies (mfERG).
Baseline and depending on risks thereafter

4. Guidelines for monitoring HCQ toxicity
(Am C Rheumatology)
 No baseline evaluation if <40, no eye disease
 F/U: visual changes, fundus & visual fields 6-12m
 Warning symptoms (night vision, glare, reading
difficulties)

5. mfERG early toxicity screening?

6.  6 symptomatic patients
– 5 pts abnormal mfERG (1 had Humph 10-2)
– Early screening device?
So SC et al 2003
 11 patients (10 asymptomatic/1 symptomatic)
– 7 pts abnormal mfERG (normal AVF)
– Preclinical toxicity?
Penrose PJ et al 2004
 15 patients
– 7 pts abnormal mfERG (3 normal HVF 30/24-2))
– mfERG useful in identifying retinal cause when VF abnormal
– may detect abnormalities earlier than other tests
Maturi RK et al 2004

7. mfERG early toxicity screening?
 Inclusion criteria:
– >5 years on hydroxychloroquine
– >18 years old
– Normal ophthalmologic exam
– Normal VF (Humphrey 10-2 Red)
– No history of retinal disease

8.  Complete ophthalmologic exam:
– VA
– Slit lamp
– Tonometry
– Color vision (Ishihara)
– Fundus
– Visual Field (Humphrey 10-2 Red)
– Red Amsler
 mfERG

9. Results
Pt # Age/ Disease Yrs Daily Cum S&S HVF mfERG
sex HCQ dose dose 10-2
1 F/60 RA 18 200 1,314g --- --- abnl
2 F/62 RA 11 400 1,606g --- --- abnl
3 F/57 ESL 15 400 2,190g --- --- abnl
4 F/46 ESL 10 2/400 1,250g --- --- abnl
5 F/52 RA 7 400 1,022g --- --- wnl
6 F/42 ESL 15 400 2,190g --- --- wnl
7 F/48 RA 13 400 1,898g --- --- wnl

10. Difference from normal
OD OS
Patient #2 Normal Patient #2 Normal

11. Patient #2
OD OS
Normal

12. CONCLUSION
 mfERG may be useful as the first indicator
of developing macular toxicity even when
the “standard” tests are normal.
 mfERG possibly should be added as an
investigation in patients at higher risk to
develop toxicity.

13. References
 Kellner U, Kraus H, Foerster MH. Multifocal ERG in chloroquine retinopathy:
regional variance of retinal dysfunction. Graefe’s Arch Clin Exp Ophthalmol (2000)
238:94-97.
 Mavikakis I, Sfikakis PP, Mavikakis E, Rougas K, Nikolau A, Kostopoulos C,
Mavikakis M. The incidence of irreversible retinal toxicity in patients treated with
hydroxychloroquine. Ophthalmology 2003, 110 (7):1321-26.
 So SC, Hedges TR, Schuman JS, Quireza MLA. Evaluation of Hydroxychloroquine
Retinopathy With Multifocal Electroretinography. Ophthalmic Surgery, Lasers &
Imaging. May/June 2003. Vol 34, No 3.
 Easterbrook M. Long-term course of Antimalarial Maculopathy after Cessation of
Treatment. Can J Ophthalmol (1992) 27 (5): 237-9.
 Carr R, Henkind P, Rothfield N, Siegel I. Ocular Toxicity of Antimalarial Drugs,
long term follow-up. Am J Ophthalmol (1968) 66: 738-44.
 Marmor M, Carr R, Easterbrook M, Farjo A, Mieler W. Recommendations on
Screening for Chloroquine and Hydroxychloroquine Retinopathy. A Report by the
American Academy of Ophthalmology. Ophthalmol (2002) 109 (7): 1377-82.
 Penrose PJ, Tzekov R, Sutter EE, Fu AD, Allen AW, Fung WE, Oxford KW.
Multifocal electroretinography evaluation for early detection of retinal dysfunction
in patients taking hydroxychloroquine. Retina 2003, 23 (4):503-512.