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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.