John M. Little

The photopic ERG luminance-response function (photopic hill): method of analysis and clinical application.

With progressively brighter stimuli, the amplitude of the photopic b-wave first increases, briefly saturates and then decreases gradually to reach a plateau, where the amplitude of the b-wave equals that of the a-wave; a phenomenon previously presented as the photopic hill. The unique presentation of this luminance-response function seriously complicates its analysis with curve fitting equations such as that of Naka-Rushton used for scotopic electroretinogram. We report a method of analysis of the photopic hill based on easily identifiable and reproducible features of the ascending and descending limbs of this function. The clinical usefulness of these parameters is illustrated with selected cases of retinal disorders.

Recording the oscillatory potentials of the electroretinogram with the DTL electrode

Suprathreshold photopic oscillatory potentials recorded with a DTL electrode were compared to those obtained with a Lovac corneal electrode. The overall oscillatory potential response (sum of oscillatory potentials) recorded with the DTL electrode was half of that obtained with the Lovac electrode. However, there was no evidence of a selective attenuation (or amplification) of any given oscillatory potential with the DTL electrode. Similarly, the oscillatory potential relative amplitude ratios and the peak times of the oscillatory potentials were identical for both electrodes. Our findings clearly indicate that the DTL electrode is adequate to record the high-frequency oscillatory potentials. Given the low cost and ease of use, as well as the disposable nature of the DTL electrode, we believe that electroretinographic specialists should seriously consider a wider utilization.

Functional decomposition of the human ERG based on the discrete wavelet transform

The morphology of the electroretinogram (ERG) can be altered as a result of normal and pathological processes of the retina. However, given that the ERG is almost solely assessed in terms of its amplitude and timing, defining the shape of the ERG waveform so that subtle, physiologically driven, morphological changes can be systematically and reproducibly detected remains a challenging problem. We examined if the discrete wavelet transform (DWT) could meet this challenge. Normal human photopic ERGs evoked to a broad range of luminance intensities (to yield waveforms of various shapes, amplitudes, and timings) were analyzed using DWT descriptors of the ERG. Luminance-response curves that were generated using the various DWT descriptors revealed distinct (p < 0.05) luminance-dependence patterns, indicating that the stimulus luminance differently modulates the various time-frequency components of the ERG and thus its morphology. The latter represents the first attempt to study the luminance-dependence of ERG descriptors obtained with the DWT. Analyses of ERGs obtained from patients affected with ON or OFF retinal pathway anomalies were also presented. We show here for the first time that distinct time-frequency descriptors can be specifically associated to the function of the ON and OFF cone pathway. Therefore, in this study, the DWT revealed reproducible, physiologically meaningful and diagnostically relevant descriptors of the ERG over a wide range of signal amplitudes and morphologies. The DWT analysis thus represents a valuable addition to the electrophysiologists armamentarium that will improve the quantification and interpretation of normal and pathological ERG responses.

The diagnostic use of the second oscillatory potential in clinical electroretinography

Of all the electroretinogram (ERG) components (a-wave, b-wave, and oscillatory potentials) only one oscillatory potential, OP2, was found to be significantly correlated with the absolute intensity of the flash stimulus (i.e., the intensity of the stimulus irrespective of the state of retinal adaptation). Our finding was further confirmed in single cell recordings of lateral geniculate unit activity in rabbits in which peak time of OP2 was found to correlate better with the geniculate activity. For these reasons we have identified OP2 as the “intensity coding” oscillatory potential of the ERG. In order to investigate if this new feature could have some clinical significance, we examined photopic ERGs recorded from patients affected with various retinopathies. In most instances the peak time of OP2 paralleled that of the b-wave, that is, in the ERG with delayed b-wave the peak time of OP2 was also delayed, while in ERGs with normal b-wave peak time the peak time of OP2 was also normal. However, in some conditions (especially in cone-rod diseases) a delayed OP2 was found in ERGs with normal b-wave peak times.

Quantifying the ON and OFF Contributions to the Flash ERG with the Discrete Wavelet Transform

Purpose Discrete wavelet transform (DWT) analyses suggest that the 20- and 40-Hz components of the short-flash photopic electroretinogram (ERG) are closely related to the ON and OFF pathways, respectively. With the DWT, we examined how the ERG ON and OFF components are modulated by the stimulus intensity and/or duration. Methods Discrete wavelet transform descriptors (20, 40 Hz and 40:20-Hz ratio) were extracted from ERGs evoked to 25 combinations of flash durations (150–5 ms) and strengths (0.8–2.8 log cd.m−2). Results In ERGs evoked to the 150-ms stimulus (to separate the ON and OFF ERGs), the 40:20-Hz ratio of ON ERGs (mean ± SD: 0.49 ± 0.04) was significantly smaller (P < 0.05) than that of OFF ERGs (1.71 ± 0.18) owing to a significantly (P < 0.05) higher contribution of the 20 and 40 Hz components to the ON and OFF ERGs, respectively. With brighter stimuli, the ON and OFF components increased similarly (P < 0.05). While progressively shorter flashes had no impact (P > 0.05) on the ON component, it exponentially enhanced (P < 0.05) the OFF component. Conclusions Discrete wavelet transform allows for an accurate determination of ON and OFF retinal pathways even in ERGs evoked to a short flash. To our knowledge, the significant OFF facilitatory effect evidenced with shorter stimuli has not previously been reported. Translational Relevance The DWT approach should offer a rapid, easy, and reproducible approach to retrospectively and prospectively evaluate the function of the retinal ON and OFF pathways using the standard (short-flash duration) clinical ERG stimulus.

Assessing the Contribution of the Oscillatory Potentials to the Genesis of the Photopic ERG with the Discrete Wavelet Transform

The electroretinogram (ERG) is composed of slow (i.e., a-, b-waves) and fast (i.e., oscillatory potentials: OPs) components. OPs have been shown to be preferably affected in some diseases (such as diabetic retinopathy), while the a- and b-waves remain relatively intact. The purpose of this study was to determine the contribution of OPs to the building of the ERG and to examine whether a signal mostly composed of OPs could also exist. DWT analyses were performed on photopic ERGs (flash intensities: −2.23 to 2.64 log cd·s·m−2 in 21 steps) obtained from normal subjects (n = 40) and patients (n = 21) affected with a retinopathy. In controls, the %OP value (i.e., OPs energy/ERG energy) is stimulus- and amplitude-independent (range: 56.6–61.6%; CV = 6.3%). In contrast, the %OPs measured from the ERGs of our patients varied significantly more (range: 35.4%–89.2%; p < 0.05) depending on the pathology, some presenting with ERGs that are almost solely composed of OPs. In conclusion, patients may present with a wide range of %OP values. Findings herein also support the hypothesis that, in certain conditions, the photopic ERG can be mostly composed of high-frequency components.

Radiation-induced chorioretinal degeneration: a clinicopathological report of three cases

BACKGROUND With the shift in radiotherapy toward the posterior segment and with the use of lead screens to shield the anterior segment, posterior segment lesions have become more readily recognized. The purpose of this study is to highlight the effects of ionizing radiation on the choroid and to demonstrate how this can result in visual loss, particularly if the macula is involved. METHODS Histopathological study of three enucleated eyes of three patients who had received ionizing radiation: a 27-year-old woman who had received radiation as a child for a hemangioma of the left side of the face, a 16-year-old girl who had received radiation at age 11 years for a malignant mesenchymoma of the right maxilla, and a 4-year-old girl who had received radiation at age 1 year for a retinoblastoma of the right eye. RESULTS Histopathological examination of the three globes showed extensive chorioretinal degeneration, among other ocular findings. In all cases the fellow eye did not show similar chorioretinal lesions. As all three patients were relatively young, the degree of chorioretinal degeneration was considered to be secondary to radiation treatment. INTERPRETATION Vascular damage from ionizing radiation is not limited to the retina. It can also affect the choroid in the form of chorioretinal degeneration. Since most of the intraocular circulation arises from the uveal vessels, chorioretinal degenerative lesions may be extensive and may even involve the macula.

Hypobaric ocular trauma from a Popper

We have observed 3 cases of ocular trauma in children that were caused by an atypical, hypobaric mechanism induced by a toy called a Popper. When we initially notified the United States Consumer Product Safety Commission in 1990, Poppers disappeared from store shelves. We are concerned that this potentially harmful toy is making a comeback in 1998 (Smilemakers Inc, Spartanburg, SC; June-July 1998 catalog, p. 57). In 1990, packaged poppers cautioned against applying to face or skin; we are not sure that such warnings accompany current Poppers.