Evaluation of the role of multifocal electroretinography in early detection of hydroxychloroquine retinal toxicity in patients with connective tissue diseases

Abstract

Purpose: To evaluate the role of multifocal electroretinography (mfERG) in early detection of hydroxychloroquine (HCQ) retinal toxicity in patients with connective tissue diseases and to correlate the results with the risk factors for development of this retinopathy. Subjects and Methods: A prospective case-control study was carried out at the Pediatric Allergy and Immunology unit, Children’s Hospital and Ophthalmology Department, Ain Shams University Hospital during the period from January 2009 to February 2010. It included 25 children, of whom 15 had connective tissue diseases without clinical signs of HCQ toxic maculopathy and ten were healthy age-matched subjects serving as controls. Children with inherited retinal degenerations and dystrophies, previous ocular surgeries or preexisting ocular diseases were excluded from the study. An informed consent was obtained from relative of each subject. All subjects underwent pediatric clinical, laboratory and complete ophthalmological evaluations. Automated 10-2 static perimetry, Full field ERG and mfERG with 61-hexagon stimulation recordings were obtained from both eyes at baseline assessment and one year later. Data were collected and compared with that of normal controls. Results: The study group included 13 females (86.67%) and two males (13.33%) with mean age of 17.13 years ± 3.14 SD in comparison to nine females (90%) and one male (10%) with the mean age 16.0 years ± 4.76 SD of the control group. 13 (86.6%) of patients had systemic lupus erythematosus (SLE), one patient (6.7%) had juvenile rheumatoid arthritis (JRA) and one patient (6.7%) had juvenile dermatomyositis. The mean duration of illness was 7.73 years ± 2.46 SD. Mean daily dose of HCQ was 3.64 mg/kg/day ± 0.6 SD. The mean duration of HCQ treatment before baseline assessment was 20.67 months ± 29.5 (range: 0.0 to 96.0 months). The mean total duration of HCQ treatment at the end of follow up was 31.06 months ± 30.76 (range: 4.0 to 108.0 months). The mean cumulative dose of HCQ before baseline assessment was 140. 27 gms ± 174.49 (range: 0.0 to 551.0 gms). The mean total cumulative dose of HCQ after one year of follow up was 204.5 gms ± 184.43 (range: 24.0 to 620.5 gms). All patients at baseline assessment had BCVA of 6/6, mean IOP of 17.13 mmHg ±1.6 SD, normal fundus appearance on ophthalmoscopy and normal visual field testing. At baseline mfERG assessment it was found that six eyes had abnormal pattern of retinal response density; three eyes had subnormal foveal response and three eyes had parafoveal subnormal response. At the follow up examination, mfERG abnormalities were observed in (11) eyes with subnormal foveal response was recorded in six eyes, parafoveal subnormal response in four eyes and one eye had generalized loss. The development of new pattern of response density abnormalities occurred in six eyes in which HCQ was continued whereas none of the eyes in which HCQ therapy was stopped (six eyes) developed new abnormalities. Reductions in N1 and P1 response amplitudes were observed in patients receiving HCQ and this was highly statistically significant in those patients who had received a cumulative dose of ≥300 gms and duration of therapy of more than five years compared with controls. Conclusion: The abnormalities in retinal electrophysiology, as detected by the mfERG, occurred earlier than any morphologic fundus change using ophthalmoscopy and static perimetry. MfERG can provide objective measurement of retinal function in those patients and provide supplementary quantitative information to visual field examination.