Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness.

During development, visual photoreceptors, bipolar cells and other neurons establish connections within the retina enabling the eye to process visual images over approximately 7 log units of illumination. Within the retina, cells that respond to light increment and light decrement are separated into ON- and OFF-pathways. Hereditary diseases are known to disturb these retinal pathways, causing either progressive degeneration or stationary deficits. Congenital stationary night blindness (CSNB) is a group of stable retinal disorders that are characterized by abnormal night vision. Genetic subtypes of CSNB have been defined and different disease actions have been postulated. The molecular bases have been elucidated in several subtypes, providing a better understanding of the disease mechanisms and developmental retinal neurobiology. Here we have studied 22 families with 'complete' X-linked CSNB (CSNB1; MIM 310500; ref. 4) in which affected males have night blindness, some photopic vision loss and a defect of the ON-pathway. We have found 14 different mutations, including 1 founder mutation in 7 families from the United States, in a novel candidate gene, NYX. NYX, which encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a new and unique member of the small leucine-rich proteoglycan (SLRP) family. The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the ON-bipolar cells, leading to the visual losses seen in patients with complete CSNB.

Can interocular pattern reversal visual evoked potential and motor reaction time differences distinguish anisometropic from strabismic amblyopia?

PURPOSE: With the use of the pattern reversal visual evoked potential and the motor reaction time, we sought to differentiate anisometropic amblyopia from strabismic amblyopia on the basis of the visual transmission time. METHODS: Pattern reversal visual evoked potentials and motor reaction times were obtained in nine normal subjects, eight anisometropic and seven strabismic amblyopes. RESULTS: Our results show that while the peak time of the pattern visual evoked potential in anisometropic amblyopia and strabismic amblyopia was significantly delayed, it could not distinguish the two types of amblyopia. In contrast, a significantly longer interocular increment in strabismics compared to anisometropes was found with the reaction time, but not with the pattern visual evoked potential. CONCLUSION: Our findings thus show that it is possible to distinguish strabismic from anisometropic amblyopes using interocular differences in reaction time measurements. Our results bring support to the contention that the two types of amblyopia represent different neural abnormalities.

Evidence supportive of a functional discrimination between photopic oscillatory potentials as revealed with cone and rod mediated retinopathies.

We report on a family where four of the eleven children presented with reduced visual acuities, a red-green deficit at the Farnsworth-Munsel FM 100-hue test, normal appearing fundi and unexpected electroretinographic findings. Light- (photopic) and dark- (scotopic) adapted electroretinograms (ERG) and oscillatory potentials (OPs) were obtained following an accepted standard protocol. The b-wave of their photopic ERG was significantly more attenuated than the a-wave due to the specific abolition of OP4, while the amplitudes of OP2 and OP3 were within the normal range, giving to the b-wave a truncated appearance reminiscent of that seen in congenital stationary night blindness (CSNB) with myopia. Interestingly in the latter condition, which is believed to result from an ON-retinal pathway anomaly, it is OP2 and OP3 which are specifically abolished while OP4 is of normal amplitude thus resulting in an OP response pattern which complements that seen with our patients. Also of interest is the fact that, in our patients, the amplitude of the dark-adapted OP2 was, on average, 240% larger than that measured in light-adaptation while, in normal, a non-significant 14% increase is noted; a finding which is in keeping with other studies reporting supernormal scotopic ERGs in some forms of cone dystrophies. Based on the photopic OP response pattern, our patients represent the electrophysiological complement of patients affected with CSNB. Interestingly their symptoms are also complementary, a finding which could support a functional discrimination between the photopic OPs.

Arthrogryposis multiplex congenita, craniofacial, and ophthalmological abnormalities and normal intelligence: a new syndrome?

We report on an 8-year-old boy with clinical manifestations suggestive of a new arthrogryposis syndrome. These included characteristic craniofacial abnormalities, cleft palate, arthrogryposis multiplex congenita, pulmonary hypoplasia, cryptorchidism, and unusual ophthalmological findings. There was no intrauterine growth retardation or decreased fetal movements. Despite the poor prognosis expected in early life, the patient presented with normal mental capability on follow-up. Family data showed that a maternal first cousin of the mother (mother's brother's son) had similar findings and died in infancy. Differential diagnosis included Pena-Shokeir syndrome or phenotype, Gordon syndrome, Marden-Walker syndrome, and the syndrome of arthrogryposis with ophthalmoplegia and retinopathy. The possibility of autosomal dominant inheritance with reduced penetrance is suggested for this apparently new syndrome.

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome).

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy syndrome is a recently described rare disorder of infantile regression, intractable seizures, and cerebellar atrophy that occurs almost exclusively in the Finnish population. We report the first North American child with this condition.

Clinical evaluation of aminocaproic acid for managing traumatic hyphema in children.

PURPOSE: The purpose of this study is to determine the incidence of secondary hemorrhage after traumatic hyphema in children and to evaluate the efficacy of epsilon aminocaproic acid in reducing this incidence. METHODS: In a prospective, randomized, double-blind study performed between November 1987 and February 1994, 94 children admitted for traumatic hyphema were assigned to receive either aminocaproic acid (n = 48) (100 mg/kg every 4 hours; maximum, 30 g daily) or placebo (n = 46) for 5 days. Patients who had ingested aspirin in the week preceding admission were excluded from the study. RESULTS: Mean age of the patients was 9.4 years. Black patients comprised 4% of the study population. Secondary hemorrhage occurred in only three patients (3.2%), two from the placebo group and one from the aminocaproic acid group, none of whom had any complications. The duration of hospital stay and the clot resorption times were increased significantly in the aminocaproic acid group (P < 0.001). CONCLUSIONS: The authors report a very low incidence of secondary hemorrhage compared with most previous studies. This difference is likely related to the small proportion of black patients in our study and to the exclusion of patients having ingested aspirin, two factors that seem to be associated with higher rates of rebleeding. The efficacy of aminocaproic acid could not be determined due to the low incidence of hemorrhage. The results of this study, however, suggest that the incidence of secondary hemorrhage in white patients without prior ingestion of aspirin is insufficient to justify routine use of aminocaproic acid in managing traumatic hyphema. Rather, an individualized decision based on the risk factors of each patient would seem more appropriate to avoid a slower clot resorption time and possible side effects of this medication.

Monocular contribution to the peak time of the binocular pattern visual evoked potential.

The contribution of each monocular pathway to the timing of the binocular pattern visual evoked potential was assessed in situations where a significant interocular timing discrepancy was observed. Monocular and binocular pattern visual evoked potentials to 0.5 degree checks were recorded from normal subjects, normal subjects in whom one eye was blurred, patients with monocular amblyopia, and patients with resolved unilateral optic neuritis. Normal subjects showed facilitation, while suppression was evidenced in subjects with monocular blurring. In patients with amblyopia, the affected pathway had no effect on binocular pattern visual evoked potential latency, suggesting that the amblyopic eye was suppressed. In contrast, all patients with optic neuritis showed binocular averaging. Our results show that different forms of binocular interaction are evidenced in normal subjects, in amblyopia and in optic neuritis, and suggest that a comparative analysis of monocular and binocular pattern visual evoked potential peak times brings valuable information to the clinical evaluation that could be used to distinguish disease processes further.

Human strabismus: evaluation of the interhemispheric transmission time and hemiretinal differences using a reaction time task.

Experimentally induced strabismus in visually immature cats leads to abnormal development of the posterior corpus callosum. This, in turn, should lead to abnormal interhemispheric integration of unilaterally presented visual information. To test whether strabismus produces deficits in the human commissural visual system, the interhemispheric transmission time (ITT) was compared in strabismic and normal subjects. Simple unimanual reaction times (RT) were tested in 30 subjects in response to a lateralized target presented monocularly at 4 degrees and 35 degrees nasally and temporally from the fovea along the horizontal meridian. This method was also used to examine the effect of strabismus on the central and peripheral portions of each hemiretina. The results showed that in strabismic subjects with or without amblyopia, the ITT did not differ significantly from normals at both eccentricities. In non-amblyopic strabismic patients, RTs in the central and peripheral portions of hemiretina were comparable to normals. However, a reduced speed of response was found in the central visual field (4 degrees) in the amblyopic eye. Our results suggest that the ITT is normal in strabismic subjects and that the longer RTs in the central portion of the nasal and temporal hemiretina of the amblyopic eye may be associated with the severe amblyopic condition.

Ocular findings and visual evoked potential response in the Prader-Willi syndrome.

It has recently been suggested that aberrant misrouting of retino-geniculate-cortical (RGC) projections, a finding previously noted only in albinism, may be an additional feature of the Prader-Willi syndrome. To determine the prevalence of ocular abnormalities in patients with the syndrome and to look for evidence of misrouted RGC projections by means of testing of the pattern-onset visual evoked potential (VEP) response, we examined 12 patients with Prader-Willi syndrome, 8 albino subjects and 5 healthy control subjects. Ocular findings in the first group included telecanthus (in five subjects), strabismus, nystagmus, foveal hypoplasia, visual field defects and cataract. However, the VEP asymmetry typically seen in albinism was not noted in any of the patients with Prader-Willi syndrome. Our findings do not support previous claims of abnormal optic nerve fibre decussation in Prader-Willi syndrome.

The importance of congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis.

We describe a family with familial adenomatous polyposis (FAP) and congenital hypertrophy of the retinal pigment epithelium (RPE). Three of five members with FAP showed flat, well-demarcated, round to oval pigmented patches of congenital hypertrophy of the RPE. We stress the importance of congenital hypertrophy of the RPE as a clinical marker in identifying patients with FAP since they are at risk for cancer.

Jaw muscle tension after succinylcholine in children undergoing strabismus surgery.

The increases in tension at the masseter and adductor pollicis muscles following succinylcholine, 1 mg.kg-1, during halothane anaesthesia were measured in eight children, 3-10 yr, with strabismus. The results were compared with those obtained in a control group of general surgical patients. Supramaximal train-of-four (TOF) stimulation was applied to the ulnar nerve and the nerve to the masseter simultaneously. Jaw closure was measured by a force transducer system. In all patients, succinylcholine caused an increase in resting tone at the jaw and at the thumb. In the strabismus group, the magnitude of this increase was 55.7 +/- 23.2 g, mean +/- SD, at the jaw and 11.3 +/- 5.6 g at the thumb. This was not significantly different from the values obtained in controls, 45.3 +/- 33.4 g and 7.9 +/- 4.2 g, respectively. The duration of the phenomenon was 1-2 min in both muscles studied, and was not statistically different in the strabismus group. Time to complete neuromuscular blockade was significantly faster at the masseter, 31 +/- 6 sec--control groups; 39 +/- 11 sec--strabismus group, than at adductor pollicis, 61 +/- 34 sec--control groups; 75 +/- 28 sec--strabismus group (P less than 0.05 and 0.013 respectively). It is concluded that succinylcholine causes similar increases in jaw tension and comparable degrees of neuromuscular blockade in patients undergoing strabismus surgery as in other children.

Jaw muscle tension after succinychloline in children undergoing strabismus surgery.

The increases in tension at the masseter and adductor pollicis muscles following succinylcholine, 1 mg · kg-1, during halothane anaesthesia were measured in eight children, 3-10 yr, with strabismus. The results were compared with those obtained in a control group of general surgical patients. Supramaximal train-of-four (TOF) stimulation was applied to the ulnar nerve and the nerve to the masseter simultaneously. Jaw closure was measured by a force transducer system. In all patients, succinylcholine caused an increase in resting tone at the jaw and at the thumb. In the strabismus group, the magnitude of this increase was 55.7 ±23.2 g, mean ±SD, at the jaw and 11.3 ±5.6 g at the thumb. This was not significantly different from the values obtained in controls, 45.3 ±33.4 g and 7.9 ±4.2 g, respectively. The duration of the phenomenon was 1-2 min in both muscles studied, and was not statistically different in the strabismus group. Time to complete neuromuscular blockade was significantly faster at the masseter, 31 ±6 sec -control groups; 39 ±11 sec -strabismus group, than at adductor pollicis, 61 ±34 sec -control groups; 75 ±28 sec -strabismus group (P < 0.05 and 0.013 respectively). It is concluded that succinylcholine causes similar increases in jaw tension and comparable degrees of neuromuscular blockade in patients undergoing strabismus surgery as in other children.

The effect of diphenylhydantoin on the electroretinogram.

Acute administration of diphenylhydantoin (DPH) in rabbits produces a significant increase in the amplitude of the a-wave. A marked increase in the amplitude of the b-wave is also noted but the time course is slower than that for the a-wave. While in controls the oscillatory potential (OP) recordings essentially consist of three major types, recordings taken after DPH injection consist of one major OP (OP2), which appears to be a result of the fusion of the original OP2 with another OP produced by the DPH injection. A similar blend of OPs was also seen in ERGs recorded from three human subjects on DPH therapy.

Abnormal dark-adapted electroretinogram in Best's vitelliform macular degeneration.

It is generally well accepted that in Best's vitelliform macular degeneration (BVMD) the electroretinogram (ERG) is normal whereas the electro-oculogram (EOG) is markedly abnormal. We describe a patient in whom BVMD was suspected on the basis of the clinical findings, EOG and family history (one of her daughters had the typical vitelliform lesion). However, her dark-adapted ERG was markedly abnormal. Similar anomalies were found in the dark-adapted ERG of the daughter. While the temporal features of the various ERG waves were well preserved, a substantial decrease in the amplitude of specific segments of the ERG signal was observed. A similar decrease in the amplitude of the oscillatory potentials was also found. We believe that this unusual combination of BVMD and abnormal dark-adapted ERG may be due to the reported reduced penetrance and variable expressivity of the BVMD gene(s).

Herpes zoster ophthalmoplegia. Report of six cases.

Ophthalmoplegia occurs infrequently in herpes zoster ophthalmicus. The third nerve appears to be the most commonly affected and the fourth nerve the least. We describe herein the clinical course of six patients with herpes zoster ophthalmoplegia. Spontaneous recovery occurred in four patients. The pathogenesis and clinical features of this syndrome are described.

Postoperative vomiting following strabismus surgery in paediatric outpatients: spontaneous versus controlled ventilation.

The study was designed to compare the frequency and severity of postoperative vomiting in paediatric out-patients receiving controlled ventilation (IPPV) or breathing spontaneously (SV) during anaesthesia for strabismus repair. One hundred and twenty unpremedicated children (ages 2-12 years) were studied in a randomized fashion. After intravenous induction of anaesthesia and tracheal intubation, patients breathed halothane 1-1.5 per cent inspired and N2O 66 per cent in O2 spontaneously (n = 60), or received IPPV, halothane 0.5-1 per cent, N2O 66 per cent, and pancuronium 0.05 mg.kg-1, which was reversed with neostigmine and atropine (n = 60). The incidence of vomiting with SV was 50 per cent (95 per cent confidence limits: 34.5-65.5 per cent) compared with 40 per cent (24.5-55.5 per cent) with IPPV (p greater than 0.25). Patients in the SV group experiencing emesis had longer operations than those not vomiting (mean +/- SEM = 1.5 +/- 0.1 vs 1.2 +/- 0.1 hours, p less than 0.005). This was not the case with IPPV. There was no correlation between age, sex, duration of surgery, or number of extraocular muscles repaired, and frequency or severity of vomiting or time to discharge. No significant advantage was afforded by IPPV over SV in the present study.

Autosomal recessive Duane's retraction syndrome.

The first two cases of probable autosomal recessive Duane's retraction syndrome, in two siblings, are reported.