Kooijman et al. (1991) described 3 unrelated Dutch patients with prolonged electroretinal response suppression (PERRS) and stationary subnormal visual acuity and photophobia. Nishiguchi et al. (2004) identified an additional Dutch patient and 1 Guatemalan patient with similar visual ... Kooijman et al. (1991) described 3 unrelated Dutch patients with prolonged electroretinal response suppression (PERRS) and stationary subnormal visual acuity and photophobia. Nishiguchi et al. (2004) identified an additional Dutch patient and 1 Guatemalan patient with similar visual complaints. All 5 patients had difficulty adjusting to changes in luminance. Walking out of a house into sunlight caused temporary blindness so severe that it necessitated immobility or assistance for 5 to 10 seconds. Visual compromise was also experienced when traveling from a bright environment to a dark one, e.g., daytime driving into a tunnel. Patients tended to avoid environments with high luminance; such environments required frequent blinking or dark sunglasses. Some patients stated that they could not participate in ball games because they could not see a moving ball. The patients' symptoms were present from early childhood. Neither the patients' symptoms nor their ocular findings, including ERGs, appreciably changed during repeat evaluations extending up to 14 years, suggesting that they may have had a stationary condition. Standard visual acuity testing (high contrast letters) revealed normal to subnormal acuities (20/20 to 20/80), with a measured acuity fluctuating from visit to visit. Optically corrected visual acuity increased in most patients by a factor of 2 with the use of pinholes, possibly owing to a reduction in retinal illuminance. One patient had a unilateral decrease in acuity (20/240 to 20/399) interpreted as amblyopia. Nishiguchi et al. (2004) evaluated the effect of contrast and movement on visual acuity in 1 patient, found to carry a homozygous mutation in the R9AP gene (607814). In this patient movement had a pronounced effect, with the most severe reduction in acuity (to a level corresponding to less than 20/200) occurring with moving, low-contrast letters. Following direct ophthalmoscopic presentation of a 9-degree diameter spot of light centered on the fovea for 10 seconds through a dilated pupil, the patient required 115 seconds to recover central visual acuity versus 11.2 +/- 3.4 seconds in controls; an heterozygote relative had a normal recovery time (11 seconds). Color vision and visual fields were normal. Final dark-adaptation thresholds were normal. Ophthalmoscopy showed no abnormalities in any of the patients' fundi. Routine ERGs showed normal rod responses to flashes of dim blue light. There was no attenuation in ERG amplitudes in response to subsequent dim blue flashes separated by 2 seconds. Rod-plus-cone ERGs to 0.5-Hz bright white flashes also showed a normal response, but only the first flash. The responses to the second flash and all subsequent flashes were markedly reduced in amplitude. As the majority of ERG amplitude in response to this flash intensity is normally mediated by rods, this reduction in amplitude suggested a rod dysfunction to Nishiguchi et al. (2004). A dysfunction also involving cones in these patients was revealed by the cone ERG responses elicited by 30-Hz white light flashes. Early responses were of normal amplitude and timing, but the responses rapidly decreased in amplitude so that the 30-Hz ERGs became nondetectable without computer averaging in about 2 seconds. On the basis of patients' symptoms and vision test results, Nishiguchi et al. (2004) concluded that their photoreceptors required an abnormally long time to adjust to changes in luminance. Slow adaptation to dim light, as exhibited by the abnormal photostress test, is also experienced by some patients who have retinitis pigmentosa or congenital stationary night blindness. What was unusual about the patients described by Nishiguchi et al. (2004) was that they were also slow to adapt to bright light. The slow adaptation of the photoreceptor resulted in a transient, incapacitating blindness when patients were suddenly confronted with a brightly lit environment. The photoreceptor defect also resulted in a severe reduction in acuity if low-contrast objects move against a bright background. The high conservation of RGS9 among vertebrates suggested that these visual abnormalities have been strictly selected against during evolution. With the recognition of the underlying photoreceptor defect and a better understanding of the patients' difficulty in adapting to changes in luminance, Nishiguchi et al. (2004) proposed the term bradyopsia (slow vision) for this clinical entity.
In the 3 Dutch patients reported by Kooijman et al. (1991) and in a fourth Dutch patient theretofore unreported, Nishiguchi et al. (2004) detected a trp299-to-arg mutation in the RGS9 gene (604067.0001). In a Guatemalan patient from a ... In the 3 Dutch patients reported by Kooijman et al. (1991) and in a fourth Dutch patient theretofore unreported, Nishiguchi et al. (2004) detected a trp299-to-arg mutation in the RGS9 gene (604067.0001). In a Guatemalan patient from a consanguineous family, Nishiguchi et al. (2004) found a frameshift mutation in the R9AP gene (607814.0001).