Quality Control Procedures and Baseline Values for Electroretinography, Perimetry, Color Vision, and Visual Acuity in an International Multicenter Study: Observations from a Safety Trial in Chronic Stable Angina Pectoris

Abstract

To describe quality control procedures and baseline values of electroretinography (ERG), kinetic and static perimetry, color discrimination, and best-corrected visual acuity from a multicenter ocular safety study. Methods: A multicenter prospective longitudinal randomized placebo-controlled study was conducted at 11 ophthalmic centers that had received certification following training, instruction, and monitoring. ERGs were obtained with the Espion E2 Ganzfeld console, perimetry with the Octopus 101 perimeter, color discrimination with the Lanthony desaturated D15 test, and best-corrected visual acuity with the Early Treatment Diabetic Retinopathy Study chart. Ophthalmic eligibility required satisfactory outcomes for ERG and perimetry by the second or third pre-inclusion attempts, respectively. Quality control for the ERG was undertaken by two central readers. Results: The mean (SD) age of the 97 individuals was 63.5 (7.9) range, 44-83 years. The overall coefficients of variation (CVs) for the ERG peak times were less than those of the only comparable single-center study. The CV for the mean defect of standard automated perimetry was approximately one-third that of the Ocular Hypertension Treatment Study. With increasing age, ERG peak times and color discrimination Total Error Score increased while ERG amplitudes and isopter area all decreased. Conclusions: The data illustrate the benefit of identical equipment, stringent on-site instruction and training, quality control, certification, and validation methods. The latter are recommended for planning and conducting multicenter trials using ERG and perimetry to monitor safety and/or efficacy of treatment intervention. Translational Relevance: Stringent quality control procedures and reliable reference values are indispensable prerequisites for informative clinical trials.

Effect of central and peripheral cone- and rod-specific stimulation on the pupillary light reflex

“…These observations are in line with the results of Cibis et al and Hu et al: Cibis et al found shorter latencies for larger stimuli and additionally a negative linear relation between the logarithm of the stimulus intensity and the pupillomotor latency [40] and Hu et al determined latency to be a function of CFD [22]. In ERG, a faster b-wave can be determined with increasing light for both rods and cones [34] which is consistent with our results as well. In contrast, latency remained nearly constant with increasing ring stimulus size for both photoreceptors.…”

Current Management of Patients with <b><i>RPE65</i></b> Mutation-Associated Inherited Retinal Degenerations in Europe: Results of a Multinational Survey by the European Vision Institute Clinical Research Network

“…As the PERCEIVE Registry does not require specific methods for VF testing, it is likely that quantitative data on the long-term effect of VN collected in all participating centers will be limited to kinetic perimetry. Unfortunately, VF data obtained with kinetic perimetry have to be interpreted with caution [35-38]. FDA encourages sponsors to explore a wide spectrum of potential clinical end points and other clinical effects in early-phase trials, such as retinal imaging, VA (low and high luminance), VFs, color vision, contrast sensitivity, and functional vision (i.e., how well the patient performs vision-related activities of daily living).…”

Three-Year Changes in Visual Function in the Placebo Group of a Randomized Double-Blind International Multicenter Safety Study: Analysis of Electroretinography, Perimetry, Color Vision, and Visual Acuity in Individuals With Chronic Stable Angina Pectoris

“…We have previously reported an age-related cross-sectional decline (<60 years of age at baseline compared with 60–79 and ≥70 years of age) in each of the 5 International Society for Clinical Electrophysiology of Vision (ISCEV), standard ERGs (standard 25 applicable at study conception), for the Lanthony desaturated D15 color vision arrangement test, for SAP, and for the I3e and the III4e isopter areas obtained by SKP. 26 These findings were derived from a 3-year multicenter, international, prospective, double-blind, randomized placebo-controlled safety study of ivabradine, a selective inhibitor of the cardiac pacemaker current (I f ), in participants with chronic stable angina pectoris who were receiving standard background anti-angina therapy (EudraCT No. 2006-005475-17).…”

“…The trial involved 97 participants in 19 cardiology centers and 11 associated ophthalmologic centers in 9 countries in Europe, Asia, South America, and Australia and used standardized equipment, stringent quality-controlled procedures, and centrally monitored procedures. 26 …”

“…This study examines the effects of age on visual function, studied longitudinally over 3 years, in the randomized-to-placebo group of individuals with stable chronic angina pectoris and unremarkable ophthalmologic findings, other than those attributable to age, who participated in the multicenter trial of ivabradine. 26 …”