Postreceptoral contribution to macular dysfunction in retinitis pigmentosa.

PURPOSE: To understand the sites of macular dysfunction in retinitis pigmentosa by evaluating focal electroretinogram (FERG) fundamental and second harmonic components, which are dominated by the activity of the outer and inner retina, respectively. METHODS: FERGs were recorded in response to a uniform field (9 degrees x 9 degrees) flickered sinusoidally at either 8 Hz or 32 Hz. The fundamental components of the responses to both the 8-Hz and 32-Hz stimuli and the second harmonic of the response to the 8-Hz stimulus were measured in their amplitudes and phases. Normal subjects (n = 17), as well as patients with typical retinitis pigmentosa (n = 22), cone dystrophy (CD, n = 7) and X-linked congenital retinoschisis (XLR, n = 5) served as subjects. The fundamental (32-Hz)-second harmonic (8 Hz) amplitude ratio was taken as an index of the relative function of outer-inner layers of the macula. RESULTS: Compared to controls, patients with retinitis pigmentosa showed losses of both FERG fundamental and second harmonic and an increase of the fundamental-second harmonic ratio. Patients with CD also showed losses of both fundamental and second harmonic, but the fundamental-second harmonic ratio was normal. Patients with XLR had a selective loss of the second harmonic, resulting in an increased fundamental-second harmonic ratio. On average, the fundamental-second harmonic ratio of patients with retinitis pigmentosa tended to increase with age. CONCLUSIONS: The results suggest that in retinitis pigmentosa, both receptoral and postreceptoral sites contribute to macular dysfunction. This differs from CD and XLR, where losses appear more selective for the outer and the inner retina. Postreceptoral losses in retinitis pigmentosa may become larger with increasing age.

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.

[Therapeutic efficacy of nicergoline in ophthalmology. Fluorescence retinographic study (author's transl)]. / Therapeutische Wirksamkeit von Nicergolin in der Ophthalmologie. Fluoreszenzretinographischer Beitrag.

10-Methoxy-1,6-dimethyl-ergolin-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) administered intravenously (8 mg) in a group of 10 healthy subjects caused a reduction of the arm-retina circulation time and a reduction of the ocular tone. The therapeutic effectiveness in 37 patients with various eye diseases was tested by administering nicergoline p.o. at a dose of 30 mg/day for 30 days and 20 mg/day as maintenance dose for 60-120 days. Positive results, in various percentages, were observed in cases of arterial obstructions, venous thrombosis, diabetic retinopathies, senile macular degenerations, papilla ischaemic oedema, central serous chorioretinopathies. Nicergoline caused no subjective or objective undesired effects.

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 first and second harmonics of the macular flicker electroretinogram: differential effects of retinal diseases.

We evaluated the effects of retinal diseases on the macular electroretinogram first and second harmonic components, which are dominated by outer and inner retinal activity, respectively. Macular electroretinograms in response to a uniform field (9 degrees x 9 degrees) flickering sinusoidally at either 32 or 8 Hz (peak frequencies of the first and second harmonics, respectively) were recorded in 14 patients with maculopathies involving photoreceptors (e.g., age-related macular degeneration), in 16 patients with postreceptoral macular diseases (e.g., branch occlusion of central retinal artery), and in 38 normal controls. Amplitude and phase of the first and second harmonic response components were evaluated by Fourier analysis. When compared to controls, patients with photoreceptor diseases had reduction in both first and second harmonic mean amplitudes and second harmonic phase delay; patients with postreceptoral diseases had normal first harmonic components but reduced and delayed second harmonic components. A discriminant analysis, by using first and second harmonic values, correctly classified 13 of 14 patients with photoreceptor diseases and 14 of 16 patients with postreceptoral disorders. These results indicate that combined evaluation of the macular electroretinogram first and second harmonic components is a useful test for identifying the site(s) of retinal dysfunction in patients with macular diseases.

Simultaneously recorded macular and paramacular ERGs in diseases affecting the central retina.

Macular and paramacular ERGs in response to two alternating checks (6 deg/side) obtained from a standard TV stimulator were recorded in 34 normal subjects and in 54 patients affected by different macular diseases. Macular ERG amplitude and the amplitude ratio between macular and paramacular ERGs (M/P ratio) were measured. In normals, the intersubjects' variability of macular ERG was comparable to that reported using different stimulation/recording techniques. Macular ERG amplitude (but not the M/P ratio) was significantly affected by age. In patients, the mean amplitude of macular ERG and the mean M/P ratio were significantly lower than normal values. At least one of these two parameters was abnormal in 78.5% of eyes with maculopathy. Both macular ERG amplitude and M/P ratio were significantly correlated with visual acuity. The present results indicate that simultaneous macular and paramacular ERGs can be easily and reliably recorded in clinical routine to evaluate macular function. This technique appears to be particularly sensitive in hereditary macular diseases in which photoreceptors are primarily involved.

Simultaneous foveal and parafoveal electroretinograms in hereditary degeneration of the central retina.

Simultaneous foveal and parafoveal electroretinograms (ERG) in response to two identical checks (6 degrees per side) alternating at constant mean luminance were recorded in 26 patients (52 eyes) affected by central hereditary chorioretinal diseases and in 14 age-matched normal subjects (14 eyes). Patients were divided into four groups according to clinical diagnoses: 1. Stargardt's disease; 2. cone dystrophy; 3. vitelliform degeneration; 4. pattern dystrophy. The amplitude and latency of the foveal ERG and the amplitude ratio between foveal and parafoveal ERG (F:PF ratio) were measured. The mean foveal ERG amplitude was significantly lower than the control mean in all patient groups. The foveal ERG latency showed a trend to a increase in all pathological groups. However, this difference was not statistically significant. The mean value of F:PF ratio was significantly reduced as compared with the control mean in Stargardt's disease and cone dystrophy only. In 46 of 52 affected eyes (88.5%) at least one of the electrophysiological parameters was abnormal. Our results suggest that the simultaneous foveal and parafoveal ERG recording may be a sensitive technique in hereditary degenerations of the central retina. This method may also contribute to a better understanding of cone degeneration pathophysiology.

Macular electroretinograms to flicker and pattern stimulation in lamellar macular holes.

Steady-state macular (9 degrees x 9 degrees) electroretinograms in response to either sinusoidal flicker (focal electroretinogram) or counterphased sinusoidal gratings (pattern electroretinogram) were recorded in 14 patients with inner lamellar macular holes, in 4 patients with full-thickness macular holes and in 14 age-matched controls. Fourier analysis of focal and pattern electroretinograms yielded three main components: a first and a second harmonic to flicker, and a second harmonic to pattern. Recent evidence indicates that the first harmonic to flicker is of receptoral origin, whereas the flicker and pattern second harmonics represent, at least in part, the activity of different generators in the inner retina. When compared to controls, patients with inner lamellar holes showed significant amplitude reduction and phase delay for both flicker and pattern second harmonics, but not for the flicker first harmonic. Patients with full-thickness holes showed significant amplitude reduction also for the flicker first harmonic. These results indicate a prevalent functional involvement of the inner retina in lamellar macular holes, which can be clinically detected by evaluating focal and pattern electroretinogram second harmonics.