Assessment of night vision problems in patients with congenital stationary night blindness.

Congenital Stationary Night Blindness (CSNB) is a retinal disorder caused by a signal transmission defect between photoreceptors and bipolar cells. CSNB can be subdivided in CSNB2 (rod signal transmission reduced) and CSNB1 (rod signal transmission absent). The present study is the first in which night vision problems are assessed in CSNB patients in a systematic way, with the purpose of improving rehabilitation for these patients. We assessed the night vision problems of 13 CSNB2 patients and 9 CSNB1 patients by means of a questionnaire on low luminance situations. We furthermore investigated their dark adapted visual functions by the Goldmann Weekers dark adaptation curve, a dark adapted static visual field, and a two-dimensional version of the "Light Lab". In the latter test, a digital image of a living room with objects was projected on a screen. While increasing the luminance of the image, we asked the patients to report on detection and recognition of objects. The questionnaire showed that the CSNB2 patients hardly experienced any night vision problems, while all CSNB1 patients experienced some problems although they generally did not describe them as severe. The three scotopic tests showed minimally to moderately decreased dark adapted visual functions in the CSNB2 patients, with differences between patients. In contrast, the dark adapted visual functions of the CSNB1 patients were more severely affected, but showed almost no differences between patients. The results from the "2D Light Lab" showed that all CSNB1 patients were blind at low intensities (equal to starlight), but quickly regained vision at higher intensities (full moonlight). Just above their dark adapted thresholds both CSNB1 and CSNB2 patients had normal visual fields. From the results we conclude that night vision problems in CSNB, in contrast to what the name suggests, are not conspicuous and generally not disabling.

Randomized controlled trial on the effects of training in the use of closed-circuit television on reading performance.

PURPOSE: To investigate the effectiveness of training in the use of closed-circuit television (CCTV) on reading performance in visually impaired patients. METHODS: In a multicenter masked randomized controlled trial, 122 patients were randomized either to a treatment group that received usual delivery instructions from the CCTV supplier combined with concise outpatient standardized training, or to a control group that received delivery instructions only. The main outcome measure was reading performance, which was obtained by measuring reading acuity, reading speed, reading errors, column-tracking time, and technical reading, approximately two weeks after patients had received their CCTV and 3 months later. Videotapes of all measurements were rated by two investigators. Training effects were analyzed with linear mixed modeling. RESULTS: There were no statistically significant differences in results between the treatment and control group. However, introducing a CCTV increased reading acuity (mean difference [MD] 0.93 logRAD; P < 0.01) and maximum reading speed (MD 15 wpm; P < 0.01), and decreased the number of errors (MD 0.33; P = 0.04), compared to reading without CCTV. Average reading speed (P = 0.05), number of errors (P = 0.04), and column-tracking time (P = 0.01) improved over time. CONCLUSIONS: Prescribing a CCTV and the delivery instructions by the supplier seemed sufficient to improve reading performance. Additional training in the use of this device did not result in further improvement. Based on these results, outpatient low-vision rehabilitation centers may consider reallocating part of the training resources into other evidence-based rehabilitation programs. (trialregister.nl number, NTR1031.).

An extended 15 Hz ERG protocol (1): the contributions of primary and secondary rod pathways and the cone pathway.

The minimum in the amplitude versus flash strength curve of dark-adapted 15 Hz electroretinograms (ERGs) has been attributed to interactions between the primary and secondary rod pathways. The 15 Hz ERGs can be used to examine the two rod pathways in patients. However, previous studies suggested that the cone-driven pathway also contributes to the 15 Hz ERGs for flash strengths just above that of the minimum. We investigated cone pathway contributions to improve upon the interpretation of (abnormal) 15 Hz ERGs measured in patients. We recorded 15 Hz ERGs in five healthy volunteers, using a range of flash strengths that we extended to high values. The stimuli were varied in both colour (blue, green, amber, and red) and flash duration (short flash and square wave) in order to stimulate rods and cones in various ways. The differences in the responses to the four colours could be fully explained by the spectral sensitivity of rods for flash strengths up to approximately 12.5 log quanta·deg(-2). At higher flash strengths, higher-order harmonics appeared in the responses which could be attributed to cones being more sensitive than rods to higher frequencies. Furthermore, the amplitude curves of the blue and green responses showed a second minimum suggesting rod to cone interactions. We present a descriptive model of the contributions of the rod and cone pathways. In clinical application, we would advise using the short flash flicker instead of the square wave flicker, as the responses are of larger amplitude, and cone pathway contributions can be recognized from large higher-order harmonics.

An extended 15 Hz ERG protocol (2): data of normal subjects and patients with achromatopsia, CSNB1, and CSNB2.

The amplitude versus flash strength curve of 15 Hz electroretinograms (ERGs) shows two minima. The minima are caused by interactions between the primary and the secondary rod pathways (first minimum), and the secondary rod pathway and the cone-driven pathway (second minimum). Furthermore, cone pathway contributions cause higher-order harmonics to occur in the responses. We measured 15 Hz ERGs in 20 healthy subjects to determine normal ranges and in patients to verify our hypotheses on the contributions of the different pathways and to investigate the clinical application. We analyzed the amplitudes and phases of the 15, 30, and 45 Hz components in the ERGs. The overall shape of the 15 Hz amplitude curves was similar in all normal subjects and showed two minima. The 30 and 45 Hz amplitude curves increased for stimuli of high flash strengths indicating cone pathway contributions. The 15 Hz amplitude curve of the responses of an achromat was similar to that of the normal subjects for low flash strengths and showed a minimum, indicating normal primary and secondary rod pathway function. There was no second minimum, and there were no higher-order harmonics, consistent with absent cone pathway function. The 15 Hz ERGs in CSNB1 and CSNB2 patients were similar and of low amplitude for flash strengths just above where the first minimum normally occurs. We could determine that in the CSNB1 patients, the responses originate from the cone pathway, while in the CSNB2 patients, the responses originate from the secondary rod pathway.

The key role of electrophysiology in the diagnosis of visually impaired children.

PURPOSE: To describe the outcome of specialized electrophysiology in visually impaired children. METHODS: We carried out a retrospective evaluation of 340 electrophysiological examinations performed in 298 children over a 3-year period (2001-2003), with regard to demographic data, referral pattern, degree of compliance, and diagnostic results. Electrophysiology was performed without sedation or anaesthesia. In electroretinograms, DTL electrodes were used in combination with online selection of responses. Visual evoked potentials testing was performed with seven active occipital electrodes. RESULTS: The mean age of the children was 7 +/- 5 years; 72 (24%) of the children were mentally as well as visually impaired. Main reasons for referral were suspected posterior segment disease, abnormal visual development, unexplained low vision, high myopia, and suspected albinism. Compliance was good in 302/340 (88%), partial in 24/340 (7%), and absent in 14/340 (4%) of the examinations. Of the 326 successful procedures, 215 (66%) showed abnormal results. Tapetoretinal dystrophy (22%), opticopathy (16%), congenital stationary night blindness (13%), and cone dystrophy (11%) were the most frequently established diagnoses. Albinism was confirmed in 14 of 24 suspected patients; additionally, unsuspected misrouting was found in six. In 26 (9%) of the patients, a previously established diagnosis was changed. CONCLUSIONS: In a specialized setting, electrophysiological examinations can be performed successfully in visually impaired children. The results are essential for the final ophthalmological diagnosis and have important consequences for rehabilitation.

Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram.

PURPOSE: Congenital stationary night blindness (CSNB) is a group of nonprogressive retinal disorders characterized by impaired night vision that occurs in autosomal dominant, autosomal recessive, or X-linked forms. Autosomal recessive (ar)CSNB seems to be very rare. Mice lacking the metabotropic glutamate receptor 6 (Grm6) have a defect in signal transmission from the photoreceptors to ON-bipolar cells. In the current study, the human orthologue (GRM6) was screened as a likely candidate for arCSNB. METHODS: arCSNB individuals of five families were screened for mutations in GRM6. Subsequently, they were examined with standard and 15-Hz flicker electroretinography (ERG). These recordings were compared with those of patients with X-linked CSNB1. RESULTS: Affected individuals in three of five families carried either compound heterozygous or homozygous mutations in GRM6. Strikingly, all of them displayed a distinctive abnormality of the rod pathway signals on scotopic 15-Hz flicker ERG. CONCLUSIONS: The novel profile identified in this study suggests the existence of more than two rod pathways. The distinctive ERG feature was not observed in patients with X-linked CSNB1 and additional affected individuals with unknown molecular defect. These observations will help to discriminate autosomal recessive from X-linked recessive cases by ERG and molecular genetic analysis.