Multifocal ERG in Multifocal ERG in Hydroxychloroquine Hydroxychloroquine

RetinopathyRetinopathy

Maria Noel Vacarezza, MDMaria Noel Vacarezza, MDPeter J Savino, MDPeter J Savino, MDRaed Behbehani, MDRaed Behbehani, MDElizabeth L Affel, MSElizabeth L Affel, MS

Hydroxychloroquine Retinal ToxicityHydroxychloroquine Retinal Toxicity

Infrequent.Infrequent. Irreversible.Irreversible. Increased by:Increased by:

– High daily (6.5mg/kg/d)(cumulative(?)) dose.High daily (6.5mg/kg/d)(cumulative(?)) dose.

– Duration of treatment (>5yrs).Duration of treatment (>5yrs).– Renal/hepatic disease.Renal/hepatic disease.– Obesity.Obesity.

– Age (>60).Age (>60).

– Concurrent retinal diseaseConcurrent retinal disease..

Current Screening Recommendations Current Screening Recommendations (AAO)(AAO)

Complete ophthalmologic examinationComplete ophthalmologic examination.. Visual field:Visual field: Humphrey 10-2 (white) Humphrey 10-2 (white) Amsler gridAmsler grid.. Color vision:Color vision: Ishihara. Ishihara. Optional tests:Optional tests:

– Fundus Photography.Fundus Photography.– IVFA.IVFA.– Electrophysiologic studies (mfERG).Electrophysiologic studies (mfERG).

Baseline and depending on risks thereafter

Guidelines for monitoring HCQ toxicity Guidelines for monitoring HCQ toxicity (Am C Rheumatology)(Am C Rheumatology)

No baseline evaluation if <40, no eye diseaseNo baseline evaluation if <40, no eye disease F/U: visual changes, fundus & visual fields 6-12m F/U: visual changes, fundus & visual fields 6-12m Warning symptoms (night vision, glare, reading Warning symptoms (night vision, glare, reading

difficulties)difficulties)

mfERG early toxicity screening?mfERG early toxicity screening?

6 symptomatic patients6 symptomatic patients– 5 pts abnormal mfERG (1 had Humph 10-2)5 pts abnormal mfERG (1 had Humph 10-2)– Early screening device?Early screening device?

So SC et al 2003So SC et al 2003

11 patients (10 asymptomatic/1 symptomatic)11 patients (10 asymptomatic/1 symptomatic)– 7 pts abnormal mfERG (normal AVF)7 pts abnormal mfERG (normal AVF)– Preclinical toxicity?Preclinical toxicity?

Penrose PJ et al 2004Penrose PJ et al 2004

15 patients15 patients– 7 pts abnormal mfERG (3 normal HVF 30/24-2))7 pts abnormal mfERG (3 normal HVF 30/24-2))– mfERG useful in identifying retinal cause when VF abnormalmfERG useful in identifying retinal cause when VF abnormal– may detect abnormalities earlier than other testsmay detect abnormalities earlier than other tests

Maturi RK et al 2004Maturi RK et al 2004

mfERG early toxicity screening?mfERG early toxicity screening?

Inclusion criteria:Inclusion criteria:– >5 years on hydroxychloroquine>5 years on hydroxychloroquine– >18 years old>18 years old

– Normal ophthalmologic examNormal ophthalmologic exam– Normal VF (Humphrey 10-2 Red)Normal VF (Humphrey 10-2 Red)– No history of retinal diseaseNo history of retinal disease

Complete ophthalmologic exam:Complete ophthalmologic exam:– VAVA– Slit lamp Slit lamp – Tonometry Tonometry – Color vision (Ishihara)Color vision (Ishihara)– FundusFundus– Visual Field (Humphrey 10-2 Red)Visual Field (Humphrey 10-2 Red)– Red AmslerRed Amsler

mfERGmfERG

ResultsResults

RA

ESL

RA

ESL

ESL

RA

RA

Disease

F/48

F/42

F/52

F/46

F/57

F/62

F/60

Age/

sex

7

6

5

4

3

2

1

Pt #

400

400

400

2/400

400

400

200

Daily dose

13

15

7

10

15

11

18

Yrs HCQ

mfERGHVF

10-2

S&SCum

dose

wnl------1,898g

wnl------2,190g

wnl------1,022g

abnl------1,250g

abnl------2,190g

abnl------1,606g

abnl------1,314g

OD OS

Normal Normal

Difference from normal

Patient #2 Patient #2Patient #2

OD OS

Normal

Patient #2

CONCLUSIONCONCLUSION

mfERG may be useful as the first indicator mfERG may be useful as the first indicator of developing macular toxicity even when of developing macular toxicity even when the “standard” tests are normal.the “standard” tests are normal.

mfERG possibly should be added as an mfERG possibly should be added as an investigation in patients at higher risk to investigation in patients at higher risk to develop toxicity.develop toxicity.

ReferencesReferences Kellner U, Kraus H, Foerster MH. Multifocal ERG in chloroquine retinopathy: Kellner U, Kraus H, Foerster MH. Multifocal ERG in chloroquine retinopathy:

regional variance of retinal dysfunction. Graefe’s Arch Clin Exp Ophthalmol (2000) regional variance of retinal dysfunction. Graefe’s Arch Clin Exp Ophthalmol (2000) 238:94-97.238:94-97.

Mavikakis I, Sfikakis PP, Mavikakis E, Rougas K, Nikolau A, Kostopoulos C, Mavikakis I, Sfikakis PP, Mavikakis E, Rougas K, Nikolau A, Kostopoulos C, Mavikakis M. The incidence of irreversible retinal toxicity in patients treated with Mavikakis M. The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine. Ophthalmology 2003, 110 (7):1321-26.hydroxychloroquine. Ophthalmology 2003, 110 (7):1321-26.

So SC, Hedges TR, Schuman JS, Quireza MLA. Evaluation of Hydroxychloroquine So SC, Hedges TR, Schuman JS, Quireza MLA. Evaluation of Hydroxychloroquine Retinopathy With Multifocal Electroretinography. Ophthalmic Surgery, Lasers & Retinopathy With Multifocal Electroretinography. Ophthalmic Surgery, Lasers & Imaging. May/June 2003. Vol 34, No 3.Imaging. May/June 2003. Vol 34, No 3.

Easterbrook M. Long-term course of Antimalarial Maculopathy after Cessation of Easterbrook M. Long-term course of Antimalarial Maculopathy after Cessation of Treatment. Can J Ophthalmol (1992) 27 (5): 237-9.Treatment. Can J Ophthalmol (1992) 27 (5): 237-9.

Carr R, Henkind P, Rothfield N, Siegel I. Ocular Toxicity of Antimalarial Drugs, Carr R, Henkind P, Rothfield N, Siegel I. Ocular Toxicity of Antimalarial Drugs, long term follow-up. Am J Ophthalmol (1968) 66: 738-44.long term follow-up. Am J Ophthalmol (1968) 66: 738-44.

Marmor M, Carr R, Easterbrook M, Farjo A, Mieler W. Recommendations on Marmor M, Carr R, Easterbrook M, Farjo A, Mieler W. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy. A Report by the Screening for Chloroquine and Hydroxychloroquine Retinopathy. A Report by the American Academy of Ophthalmology. Ophthalmol (2002) 109 (7): 1377-82.American Academy of Ophthalmology. Ophthalmol (2002) 109 (7): 1377-82.

Penrose PJ, Tzekov R, Sutter EE, Fu AD, Allen AW, Fung WE, Oxford KW. Penrose PJ, Tzekov R, Sutter EE, Fu AD, Allen AW, Fung WE, Oxford KW. Multifocal electroretinography evaluation for early detection of retinal dysfunction Multifocal electroretinography evaluation for early detection of retinal dysfunction in patients taking hydroxychloroquine. Retina 2003, 23 (4):503-512.in patients taking hydroxychloroquine. Retina 2003, 23 (4):503-512.