Evaluation of cone function by a handheld non-mydriatic flicker electroretinogram device

Abstract

Purpose: Full-field electroretinograms (ERGs) are used to evaluate retinal function in patients with various types of hereditary and acquired retinal diseases. However, ERG recordings require relatively invasive procedures, including pupillary dilation and the use of contact lens electrodes. Thus, it would be helpful to have a simpler and noninvasive screening method. The purpose of this study was to determine whether a new, handheld, portable ERG device, RETeval™, can be used to screen patients for cone dysfunction.

Patients and methods: Thirty-five eyes of 35 patients who had reduced cone responses ascertained by a conventional ERG system using contact lens electrodes were studied. The causative diseases included achromatopsia, cone dystrophy, cone-rod dystrophy, retinitis pigmentosa, choroidal dystrophy, autoimmune retinopathy, and Stargardt disease. The flicker ERGs were recorded with the RETeval™ under undilated conditions with skin electrodes (stimulus strength, 3.0 cd·s/m(2); frequency, 28.3 Hz), and the responses were compared to that of 50 healthy eyes. The amplitudes and implicit times of the fundamental component of the flicker ERGs were analyzed in three age groups: Group A, ≤20 years; Group B, 21-40 years; and Group C, ≥41 years.

Results: In all of the age groups, the amplitudes of the ERGs were significantly smaller and the implicit times significantly longer in patients with cone dysfunction than in the control eyes. All but one of the patients had flicker amplitudes lower than the mean -2.0 standard deviation of control eyes.

Conclusion: The RETeval™ has a potential of being used to screen for cone dysfunction. The entire examination takes <5 minutes and does not require pupil dilatation or a contact lens electrode. Although the flicker responses do not provide information on the scotopic functions, the RETeval™ device can be used to determine which patients require additional full-field ERG testing with dilated pupils under both scotopic and photopic conditions.

Keywords: RETeval™; cone dysfunction; flicker ERG; retina.

Figure 1

Amplitudes and implicit times of the ERGs recorded with the RETeval™ device. Notes: Scatterplot of the amplitudes and implicit times of the RETeval™ ERGs recorded from patients with cone dysfunction (red) and controls (black). The implicit time was not measurable in 14 of 35 eyes due to extremely low amplitude because of the cone dysfunction. Abbreviation: ERGs, electroretinograms.

Figure 2

Scatterplots showing the relationship between the results obtained by the RETeval™ and conventional ERG in patients with cone dysfunction. Notes: There was a significant positive correlation in the amplitude (r=0.576, P<0.001, n=35; Pearson correlation coefficient). It should be noted that pupils were not dilated for the RETeval™ but were dilated for the conventional ERGs. Abbreviation: ERGs, electroretinograms.

Figure 3

An 8-year-old boy diagnosed with cone-rod dystrophy. Notes: (A) Fundus photographs of the patient. (B) Conventional full-field ERGs: (top panel): Patient; (bottom panel): Normal subject. (C) RETeval™ ERGs from patient (left and middle) and control (right). The ophthalmoscopic appearance was normal, but flicker ERG responses were extinguished both in the conventional ERGs and the RETeval™ ERGs. The sinusoidal lines in red represent the fundamental component of the RETeval™ ERGs, and the black lines indicate the reconstructed flicker ERG waveform, which is the combination of first eight harmonics. The normal example of the RETeval™ ERG was taken from a 7-year-old boy. The pupil diameters of the patient and normal subject are 5.0 and 4.0 mm, respectively. Abbreviation: ERGs, electroretinograms.

Figure 4

A 4-year-old boy whose older sister and father were diagnosed with retinitis pigmentosa. Notes: (A) Fundus photographs of the patient. (B) RETeval™ ERGs from this patient (left and middle) and a control (right). The ophthalmoscopic appearance was normal, but the RETeval™ showed reduced amplitudes in both eyes; lower than the mean −2.0 standard deviations of normal eyes. This patient did not agree to have conventional ERG recordings with contact lens electrodes. The normal example of the RETeval™ ERG was taken from a 7-year-old boy. The pupil diameters of the patient and normal eye are 5.5 and 4.0 mm, respectively. The sinusoidal lines in red represent the fundamental component of the RETeval™ ERGs, and the black lines indicate the reconstructed flicker ERG waveform, which is the combination of first eight harmonics. Abbreviation: ERG, electroretinogram.

Figure 5

A 23-year-old male with achromatopsia and a 61-year-old male suspected of autoimmune retinopathy. Notes: (A) Fundus photographs (upper left), RETeval™ ERGs (upper right), and conventional full-field ERGs (middle and bottom) of a 23-year-old male diagnosed with achromatopsia. (B) Fundus photographs (upper left), RETeval™ ERGs (upper right), and conventional full-field ERGs (middle and bottom) of a 61-year-old male who was suspected of having autoimmune retinopathy. In both cases, cone dysfunction of the affected eyes was detected by the RETeval™ ERGs. The normal examples of the RETeval™ ERGs were taken from a 35-year-old female. The pupil diameters of the patients in (A), (B), and normal eye are 5.5, 3.5, and 4.5 mm, respectively. The sinusoidal lines in red represent the fundamental component of the RETeval™ ERGs, and the black lines indicate the reconstructed flicker ERG waveform, which is the combination of first eight harmonics. Abbreviation: ERGs, electroretinograms.

Figure 5

A 23-year-old male with achromatopsia and a 61-year-old male suspected of autoimmune retinopathy. Notes: (A) Fundus photographs (upper left), RETeval™ ERGs (upper right), and conventional full-field ERGs (middle and bottom) of a 23-year-old male diagnosed with achromatopsia. (B) Fundus photographs (upper left), RETeval™ ERGs (upper right), and conventional full-field ERGs (middle and bottom) of a 61-year-old male who was suspected of having autoimmune retinopathy. In both cases, cone dysfunction of the affected eyes was detected by the RETeval™ ERGs. The normal examples of the RETeval™ ERGs were taken from a 35-year-old female. The pupil diameters of the patients in (A), (B), and normal eye are 5.5, 3.5, and 4.5 mm, respectively. The sinusoidal lines in red represent the fundamental component of the RETeval™ ERGs, and the black lines indicate the reconstructed flicker ERG waveform, which is the combination of first eight harmonics. Abbreviation: ERGs, electroretinograms.

Figure 6

The extended protocol of RETeval™ for both photopic and scotopic conditions with dilated pupils. Notes: (A) RETeval™ ERGs recorded from a 5-year-old boy whose older sister and father were diagnosed with retinitis pigmentosa (pupil diameter, 8.0 mm). The ERG responses were almost extinguished under both scotopic and photopic conditions, and we confirmed that this patient had retinitis pigmentosa. (B) RETeval™ ERGs recorded from a normal eye of a 30-year-old female (pupil diameter, 8.5 mm). Abbreviation: ERGs, electroretinograms.