The fundamental and second harmonic of the photopic flicker electroretinogram: temporal frequency-dependent abnormalities in retinitis pigmentosa.

OBJECTIVES: The flicker electroretinogram (FERG) consists mainly of a linear (fundamental, 1F) and a non linear (second harmonic, 2F) component. Previous results indicate that 2F originates more proximally in the retina than 1F, and that retinitis pigmentosa (RP) may affect 2F to a greater extent than 1F. The aim of this study was to evaluate FERG 1F and 2F abnormalities in RP as a function of the stimulus temporal frequency (TF). METHODS: Twelve patients with typical RP and 10 age-matched controls were examined. FERGs were recorded in response to uniform fields (18 degrees) presented in the macula on a light-adapting background. Stimuli were flickered sinusoidally at different, closely spaced TFs between 3.7 and 52 Hz. Amplitudes and phases of the Fourier analysed 1F and 2F components were measured. Components' apparent latencies were estimated from the rate at which phase lagged with TF. RESULTS: When compared to controls, mean 1F amplitudes of patients were reduced at both low (3.7-12.6 Hz) and high (14-52 Hz) TFs, with greatest losses (0.5 log units) around the peaks (3.7 and 41 Hz) of the normal TF function. Mean 2F amplitudes were reduced mainly at low TFs, with greatest losses (0.5 log units) at 5-8 Hz. On average, the shape of the 2F, but not 1F amplitude versus TF function, differed between patients and controls, showing a selective attenuation at low TFs. Mean 1F apparent latencies were delayed at both low and high TFs, with greater delays at low (85 ms) than at high (33 ms) TFs. Mean 2F apparent latencies were delayed only at low TFs (58 ms). CONCLUSIONS: In RP, 1F and 2F phase delays as well as 2F amplitude losses are dependent on TF, suggesting that FERG generators' subpopulations in both distal and proximal retina are differentially affected. Analysis of the FERG TF response is potentially useful to characterize cone system dysfunction in different genetic subtypes of RP.

A new device for ocular surgical training on enucleated eyes.

OBJECTIVE: To develop a reliable inexpensive device for teaching ocular surgical procedures and practicing experimental techniques on enucleated eyes. DESIGN: Teaching device trial. PARTICIPANTS: Thirty enucleated porcine eyes. METHODS: A Plexiglas ocular bulb holder was secured with its base support to a polyvinylchloride pillar on a modified polystyrene trial head. MAIN OUTCOME MEASURE: The convenience and reproducibility of both laser and surgical ocular techniques performed with this new device were evaluated. RESULTS: This model allows curvilinear capsulorrhexis and phacoemulsification of porcine lenses through a corneal tunnel incision and insertion of a soft foldable acrylic intraocular lens into the capsular bag. Argon and neodymium:YAG laser iridotomy and retinal argon laser photocoagulation can also be performed with this model. CONCLUSIONS: This inexpensive device is useful for teaching both surgical and laser ocular procedures.

Retinal ganglion cell dysfunction in humans following post-geniculate lesions: specific spatio-temporal losses revealed by pattern ERG.

Nasal and temporal hemifield (14 x 24 degrees) pattern electroretinograms (PERGs) were recorded in eight patients (age range: 21-72 years) suffering from different post-geniculate lesions (documented by CT scan and/or MRI of the brain) and homonymous hemianopia at visual field testing. In total eight age-matched normal subjects served as controls. PERGs were elicited by alternating, sinusoidal gratings (90% contrast), whose spatial and temporal characteristics, 6 Hz-5 c deg-1 and 15 Hz-0.58 c deg-1, were chosen to enhance the relative contributions of parvo- (P) and magno- (M) retinal ganglion cell (GC) subsystems, respectively. Amplitudes and phases of the Fourier analyzed PERG 2nd harmonics were measured. In normal subjects, PERG amplitudes to 15 Hz-0.58 c deg-1, but not those of the 6 Hz-5 c deg-1 stimuli were on average larger (P < 0.05) in nasal than in temporal hemiretinae. In hemianopic patients, PERG amplitudes of 6 Hz-5 c deg-1 stimuli were on average reduced (P < 0.05) in the hemiretinae corresponding to blind hemifields, in comparison to those in the hemiretinae corresponding to functional hemifields. No differences between hemiretinae were observed for responses of the 15 Hz-0.58 c deg-1 stimuli. In both normal subjects and patients, average PERG phases did not differ between hemiretinae, while changing significantly (P < 0.01) across stimulus conditions. The PERG naso-temporal asymmetries observed in normal subjects are consistent with the reported asymmetries in GC density observed histologically (Curcio & Allen. (1990). Journal of Comparative Neurology, 300, 5-25). The results in patients indicate that the PERGs to specific spatio-temporal stimuli (i.e. of relatively low-temporal and high-spatial frequency), presented in the hemianopic field, are reduced in amplitude. This suggests, in agreement with the experimental findings in monkeys (Cowey & Stoerig. (1991). Trends in Neuroscience, 14, 140-145), that retrograde trans-synaptic dysfunction of P-GCs, with relative sparing of the M-subsystem, may occur in humans following lesions of post-geniculate pathways.

Focal electroretinograms and fundus appearance in nonexudative age-related macular degeneration. Quantitative relationship between retinal morphology and function.

BACKGROUND: The aim of this study was to evaluate the focal electroretinogram (FERG), an objective indicator of outer retinal function, in nonexudative age-related macular degeneration (NE-AMD), and to compare FERG results with morphological lesions assessed by stereoscopic fundus photographs and fluorescein angiograms. METHODS: Twenty-five patients (25 eyes) with bilateral NE-AMD (visual acuity of the study eyes > or = 0.4) as well as 10 age- and sex-matched control subjects (10 eyes) were evaluated. FERGs were recorded from the macular region (9 degrees) in response to sinusoidal stimuli flickered at 32 Hz. Amplitude and phase angle of the Fourier-analyzed FERG fundamental component were measured. Fundus lesions were graded from color slides according to the Wisconsin age-related maculopathy grading system . Fluorescein angiograms were evaluated by an image analysis technique to compute the area with pathological hyperfluorescence (associated with drusen and/or retinal pigment epithelial atrophy) within the macular (approximately 9 degrees x 9 degrees) region. RESULTS: Compared to control eyes, NE-AMD eyes had a reduction in the mean FERG amplitude (57% loss, P<0.001) with no phase changes. Amplitudes of individual affected eyes were negatively correlated with either the Wisconsin grading score (r = -0.63, P < 0.001) or the percentage area of pathological hyperfluorescence (r = -0.70, P<0.01). Eyes with minimal NE-AMD lesions (Wisconsin score < or = 6) and normal acuity had a lower mean amplitude (47% loss, P < 0.05) than that of control eyes. CONCLUSIONS: The results indicate that, in NE-AMD, the FERG is altered in parallel with the extent and severity of fundus lesions. However, a functional impairment of outer macular layers, which is detected by FERG losses, could precede morphological changes typical of more advanced disease.

The spatial tuning of steady state pattern electroretinogram in multiple sclerosis.

In normal subjects, the steady-state electroretinogram in response to contrast reversing gratings (PERG), is spatially band-pass tuned in amplitude, with a maximum at intermediate spatial frequencies and an attenuation at lower and higher ones. The amplitude attenuation at low spatial frequencies is believed to reflect centre-surround antagonistic interactions in the receptive fields of inner retinal neurons. The aim of this study was to evaluate the PERG spatial tuning in multiple sclerosis (MS) patients without a previous optic neuritis history. Steady- state PERGs in response to counterphase-modulated (8 Hz) sinusoidal gratings of variable spatial frequency (0.6, 1.0, 1.4, 2.2 and 4.8 c/deg), were recorded from 18 patients with definite or probable MS and no history of optic neuritis (ON-). Nine of them had no signs of subclinical optic nerve demyelination (asymptomatic) in either eye, while nine had symptoms or signs of optic pathways involvement (symptomatic) in one or both eyes. Results were compared with those obtained from 10 MS patients with a previous history of optic neuritis (ON+) in one or both eyes, as well as from 21 age-matched controls. The amplitudes and phases of the responses' 2nd harmonics were measured. Compared with the controls, asymptomatic ON- patients showed selective losses in mean PERG amplitudes at medium and high (1.0-4.8 c/deg) spatial frequencies. Symptomatic ON- patients and ON+ patients had reductions in mean PERG amplitudes, with respect to controls, involving the whole spatial frequency range, but with greater losses at medium-high (1.0-4.8 c/deg) than at lower spatial frequencies. In all patients' groups, the average PERG spatial tuning function differed significantly from that of the controls, assuming a low-pass instead of the normal band-pass shape. The PERG phase was delayed in ON+ but not in ON- patients, as compared to controls. However, the phase delay was independent of spatial frequency. In both ON- and ON+ patients, losses in PERG amplitude and spatial tuning tended to be associated with corresponding abnormalities in perimetric sensitivity, visual acuity, colour vision and transient visual evoked potential (VEP) latency. The results indicate that abnormalities of the spatial tuning of steady-state PERG can be found in MS patients without either optic neuritis or signs of subclinical optic nerve demyelination. These changes may reflect a retinal dysfunction, developing early in the course of MS, due to a loss of specific subpopulations of inner neurons, changes in lateral interactions of their receptive fields, or both.

Transiently raised intraocular pressure reveals pattern electroretinogram losses in ocular hypertension.

PURPOSE: It is known that the pattern electroretinogram (PERG) of normal subjects is reduced temporarily after short-term elevation of intraocular pressure (IOP). The authors evaluated PERG changes in ocular hypertension during and after transient IOP elevation. METHODS: Steady state (8 Hz) PERGs to sinusoidal gratings (1.7 cyc/deg spatial frequency) were recorded in seven untreated patients with ocular hypertension at medium risk (maximum IOP, 22 to 25 mm Hg; cup-disk ratio, 0.6 to 0.7; normal Humphrey 30-2 visual field results; positive family history), as well as in six age-matched normal subjects. Recordings were obtained for the baseline condition during a short-term (6-minute) IOP elevation (to 30 mm Hg) by using a suction cup apparatus and during a 6-minute recovery period after removal of the apparatus. RESULTS: During IOP elevation, PERG amplitudes were reduced significantly from baseline values in normal subjects and patients. However, PERG losses were significantly greater in patients (average loss from baseline after 4 minutes of IOP elevation: 72% +/- 7.6%) compared to controls (average loss after 2 minutes of IOP elevation: 40% +/- 7.5%). In the recovery phase, mean PERG amplitude returned to baseline values in normal subjects but not in patients, whose recovery took longer. In normal subjects, PERG phase did not change either during or after IOP elevation. In patients, however, PERG phase showed a delay from baseline during and after IOP elevation (average delay after 6 minutes of recovery: -41.1 degrees +/- 13 degrees). CONCLUSIONS: Results indicate that increasing IOP with scleral suction produces greater PERG losses in eyes with ocular hypertension than in normal eyes. This suggests that the inner retina of eyes with ocular hypertension may have a heightened sensitivity to vascular or mechanical changes induced by transient IOP elevation.

Macular flicker electroretinograms in Best vitelliform dystrophy.

PURPOSE: The aim of this study was to evaluate the function of the neurosensory retina in Best vitelliform macular dystrophy (BMD) by recording the focal electroretinogram (ERG) fundamental and 2nd harmonic components, which are known to be dominated by receptoral and postreceptoral activity, respectively. METHODS: FERGs were recorded in response to a uniform field (9 x 9 deg) flickered sinusoidally at either 8 Hz or 32 Hz (peak frequencies for the 2nd and fundamental harmonic, respectively). The fundamental component of the response to the 32-Hz stimulus and the 2nd harmonic of the response to the 8-Hz stimulus were measured in their amplitudes and phases. The fundamental-2nd harmonic amplitude ratio was taken as an index of the relative changes in the FERG components. Eleven patients with BMD and vitelliform stage macular lesions were evaluated. Results were compared with those obtained from 13 patients with Type 2 Stargardt macular dystrophy (STD) according to the Noble and Carr Classification, and 29 normal control subjects. Four BMD and four STD patients were also followed electrophysiologically over a 48 month period. RESULTS: Compared to controls, BMD patients showed losses of both FERG fundamental and 2nd harmonic amplitudes, and an increase in the fundamental and increase in the fundamental-2nd harmonic ratio. STD patients also showed losses of both fundamental and 2nd harmonic, but the fundamental-2nd harmonic ratio was normal. In BMD patients, but not in those with STD, the fundamental amplitude tended to decrease over the follow-up period. CONCLUSIONS: The results indicate that BMD involves neurosensory abnormalities early in the disease process. The increased fundamental-2nd harmonic ratio suggests that a postreceptoral dysfunction may be present in addition to that of photoreceptors. This differs from STD, where losses appear to affect primarily the receptoral retina. Receptoral losses in BMD may progress throughout the medium-term follow up.

Pattern electroretinograms and visual evoked potentials in idiopathic intracranial hypertension.

A subclinical visual dysfunction can be detected by psychophysical methods in early-stage papilledema associated with idiopathic intracranial hypertension (IIH). We recorded steady-state pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) to sinusoidal gratings of variable spatial frequency [0.6, 1.0, 1.4, 2.2 and 4.8 cycles/degree (cpd)] in 18 patients with IIH and early papilledema and in 21 age-matched controls. Spatial frequency selective reductions in the mean PERG (at 1-4.8 cpd) and VEP (at 4.8 cpd) amplitudes were found in patients in comparison with controls. The response functions of amplitude versus spatial frequency of patients' PERG and VEP displayed a low-pass shape, whereas in normal subjects PERG and VEP functions showed a band-pass and a high-pass shape, respectively. PERG and VEP abnormalities were found in 14 (77.7%) and 10 (55.5%) out of 18 patients, respectively. Most of these abnormalities involved only selected spatial frequencies (1.4-4.8 cpd). These results indicate spatial-frequency-dependent functional losses on both PERG and VEP in early papilledema, and suggest a potential value of these responses for detecting subtle visual abnormalities in IIH.

Pattern electroretinogram as a function of spatial frequency after retrobulbar optic neuritis.

Steady-state (8-Hz) pattern electroretinograms in response to counterphased sinusoidal gratings of variable spatial frequency (0.6-4.8 c/deg) were recorded in 17 patients who had had retrobulbar optic neuritis in one or both eyes (23 eyes with a clinical history of optic neuritis) and in 21 age-matched normal subjects. Amplitude and phase of the Fourier-analyzed pattern electroretinogram second harmonic were measured. The mean pattern electroretinogram amplitude of patients was significantly reduced compared with that of controls. Amplitude reductions were more marked at intermediate (1-1.4 c/deg) than at lower or higher spatial frequencies. Therefore, the average amplitude versus spatial frequency response function differed significantly in patients compared with controls, displaying a lowpass instead of a band-pass shape. No significant differences in the mean pattern electroretinogram phase were observed between groups at any spatial frequency. These results indicate spatial frequency-dependent abnormalities in the pattern electroretinogram amplitude after optic neuritis, suggesting a specific loss of retinal neurons sensitive to stimuli of intermediate spatial frequencies.