144 2 Hereditary Retinal and Allied Diseases
Some unusual forms of retinal dysfunction have been reported that involve the cone and the rod photoreceptor systems in an extraordi- nary way. With the rod–cone dysfunction syndrome, there is decreased sensitivity to light while at the same time its responsiveness to superthreshold light stimuli is enormously augmented [1–3].
This unusual combination is illustrated in three of our patients [4]. A 15-year-old girl (case 1), an 11-year-old girl (case 2), and a 32- year-old woman (case 3) had low visual acuity of 0.1–0.4 with moderate to high myopia from birth. The family history was negative in the three patients. Night blindness was detected by dark-adaptation curves with elevation of the final rod thresholds by 1.5–2.3 log units. The visual fields were almost normal except for slight constriction with small and dim targets.
The color vision was markedly abnormal, with a scotopic pattern similar to that of rod monochromats. The fundus and fluorescein angiograms are essentially normal (Fig. 2.120), except for bull’s-eye maculopathy in case 1 and slight optic atrophy in case 3. We have followed two of these patients for more than 10 years, and the clinical condition has not changed (i.e., it is stationary).
The standard full-field ERGs recorded from these three patients are shown in Fig. 2.121.
Compared with the results of age-matched normal young subjects, the amplitude of the scotopic (rod) ERG was markedly reduced, and the implicit time was delayed. The photopic (cone) and 30-Hz flicker ERGs were almost undetectable. The bright-flash mixed rod–cone ERG was markedly altered; the a-wave had a
step-like configuration, the OPs were reduced, and the b-wave amplitude was supernormal.
The changes in the ERGs elicited by white flash stimuli of various intensities are shown in Fig. 2.122. Despite the undetectable b-wave recorded with dim stimuli, the b-wave became supernormal when recorded with stronger stimuli. The most remarkable aspect of this dis- order is demonstrated in Fig. 2.122. The thresh- old, amplitude, and waveform of the flash ERGs are abnormal. The stimulus threshold is ele- vated by approximately 3.5 log units in all patients; but as the intensity of the stimulus is increased, the responses become larger in an extraordinary fashion. When the stimulus is high, the a-wave has been almost step-like in its waveform, and its amplitude is smaller than normal. On the other hand, the b-wave is super- normal with a normal implicit time.
The ERG findings of this disorder are some- what similar to those of the enhanced S-cone syndrome (i.e., markedly reduced or absent rod and 30-Hz flicker ERGs, supernormal b-wave, and step-like a-wave. However, the definitive differences are the markedly reduced or unde- tectable photopic (cone) and blue-cone ERGs.
It is possible experimentally to produce changes similar to those observed in these patients by increasing the intracellular cyclic guanosine monophosphate (cGMP) in rods in several ways. These experimental conditions produce an increase in the amplitude, prolon- gation in the time course, and steepening of the intensity-response curve of the rod photore- ceptor responses [5].
These experimental results may provide the key to solving the unique paradox of the
2.17 Rod–Cone Dysfunction
Syndrome with an Unusual Form of ERG
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2.17 Rod-Cone Dysfunction Syndrome with an Unusual Form of ERG 145
elevated subjective dark-adapted thresholds associated with the supernormal responses in bright flash ERG in the dark-adapted condi- tion. However, we have measured the cyclic
nucleotide levels in the blood and urine of these patients, and our results did not show any significant abnormality, although the values were slightly higher than normal.
Fig. 2.120. Fundus of a patient (case 3) with an unusual form of supernormal ERG
Fig. 2.121. Full-field ERGs recorded from three patients with rod–cone dysfunction showing an unusual ERG waveform. Despite the undetectable rod and cone ERGs, the mixed rod–cone ERG with intense stimuli shows a supernormal b-wave with a step-like a-wave. (From Yagasaki et al. [4])
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146 2 Hereditary Retinal and Allied Diseases
References
1. Abraham FA, Sandber MA (1977) An unusual type of juvenile foveal dystrophy: electrophysiologic study. Doc Ophthalmol Pro Series 11:75–83 2. Alexander KR, Fishman GA (1984) Supernormal
scotopic ERG in cone dystrophy. Br J Ophthalmol 68:69–78
3. Gouras P, Eggers HM, MacKay CJ (1983) Cone dys- trophy, nyctalopia, and supernormal rod responses:
a new retinal degeneration. Arch Ophthalmol 101:
718–724
4. Yagasaki K, Miyake Y, Litao RE, Ichikawa K (1986) Two cases of retinal degeneration with unusual form of electroretinogram. Doc Ophthalmol 63:73–
82
Fig. 2.122. Intensity-response series for the ERGs recorded from a normal control and the three patients whose ERGs are shown in Fig. 2.121. (From Yagasaki et al. [4])
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