[Functional vision disorder: timely examination pays off]. / Functionele visusklachten: tijdig onderzoek loont.

Patients with functional vision disorder (FVD) may present with poor visual acuity, visual field loss, or a combination of the two. This paper illustrates the utility of objective tests in diagnosing FVD. We use sweep visual evoked potentials and eye tracking as objective tests for visual acuity and visual field, respectively. These measurements should be made early in the diagnostic process because appropriate treatment becomes more difficult the longer the patient has been undergoing medical workups and referrals. Additionally, objective proof of better visual functions can be used as confirmation of the absence of a serious organic disorder. The results are used to convince patients and parents that vision is potentially much better than the patient experiences and to explain FVD. Consultation should preferably take place in a multidisciplinary setting with trained ophthalmologists and psychologists.

Chiasmal misrouting and foveal hypoplasia without albinism.

BACKGROUND/AIMS: To present the ophthalmological and electrophysiological characteristics of three darkly pigmented, female patients with misrouting and foveal hypoplasia. One of the patients had primary ciliary dyskinesia and situs inversus totalis (Kartagener syndrome). METHODS: Fundus photographs were taken and the angles at which the main temporal arterial branches leave the optic nerve head (ONH) were analysed. Optical coherence tomography (OCT) was performed through the presumed foveal region. Pattern onset visually evoked potentials (VEPs) (check sizes 60', 40/400 ms) were recorded and the chiasmal coefficient was calculated to detect misrouting. RESULTS: Fundus photography showed normally pigmented fundi with absence of the usual foveal hyperpigmentation, foveal avascular zone, and macular and foveal reflexes. On OCT no foveal pit was found. The VEP recordings showed the largest positive CI component over the right hemisphere for the left eye, and over the left hemisphere for the right eye, with the CI almost absent over the ipsilateral hemispheres. The differential derivations showed opposite polarity for the recordings of the two eyes. The chiasmal coefficients of all three patients were significantly indicative of misrouting (-0.99, -0.91, and -0.99, respectively). CONCLUSION: Based on the investigations in these patients the authors propose the hypothesis that foveal hypoplasia and misrouting exist as a distinct entity, and do not comprise the exclusive hallmark of albinism. The findings suggest that misrouting may exert a retrograde influence on foveal development.

Visual event-related potentials in cirrhotic patients without overt encephalopathy: the effects of flumazenil.

The P300 complex was derived from the electroencephalogram (EEG) as subjects mentally counted infrequent large checkerboard visual stimuli, presented randomly among frequent small checkerboard stimuli. Use of low contrast (10%) stimuli and four midline scalp electrodes, facilitated separation of cognitive and sensory components and enabled the P300 complex to be resolved into three distinct components--N200, P3a, and P3b. In 20 healthy adult subjects normative data were established and the P3a and P3b components were shown to depend on cognitive function. In 19 age-matched cirrhotic patients without overt hepatic encephalopathy (HE) the EEG and visual evoked potentials (VEPs) were normal, but latencies of P3a and/or P3b were prolonged in 9. Prolonged latencies were not associated with an abnormal number connection test. Ten additional age-matched cirrhotic patients without overt HE, who were alcohol, drug, and caffeine free, were randomized to receive flumazenil (1 mg) and placebo intravenously, double-blind. After flumazenil or placebo, latencies of P3a and P3b and psychometric test results did not change significantly. These findings suggest that in cirrhotic patients without overt HE (i) impaired cognitive sensory function may occur in the absence of abnormalities of a standard psychometric test, the EEG, or VEPs, and (ii) increased latencies of P3a and P3b may constitute a component of subclinical HE, which is not mediated by increased brain levels of central benzodiazepine receptor agonist ligands.

Ocular features in Rubinstein-Taybi syndrome: investigation of 24 patients and review of the literature.

AIMS: To delineate the nature and frequency of ocular pathology in Rubinstein-Taybi syndrome (RTs). METHODS: Literature was searched for reports describing ocular symptoms in patients with RTs. 24 RTs patients (out of a total of 73 Dutch known RTs individuals) were selected for ophthalmological and electrophysiological examination, selection being based only on the distance between a patient's residence and the place of investigation. RESULTS: Most frequently reported eye anomalies in the literature were lacrimal duct obstruction, corneal abnormalities, congenital glaucoma, congenital cataract, and colobomata. Abnormalities of almost any eye segment have been published in case reports. Ophthalmological examination of 24 Dutch RTs patients showed a visual acuity

Visual event-related potentials in cirrhotic patients without overt encephalopathy.

UNLABELLED: Ambulant patients with cirrhosis and no clinical evidence of encephalopathy were screened for impaired brain function by neuroelectrophysiological testing dependent on cognitive function. Infrequent large checkerboard visual stimuli were randomly interleaved with frequent small ones to elicit P300 event-related potentials (ERPs). Three ERP components, N200, P3a and P3b, were derived from the electroencephalogram (EEG) by computer averaging. The use of 10% contrast and a minimum of four precisely placed scalp electrodes were found to be necessary for optimal separation of ERPs from sensory evoked potentials. Visual ERPs, onset/offset and pattern-reversal visual evoked potentials (VEPs), the spontaneous EEG and the time taken to complete a standard number connection test (NCT) were obtained from 20 normal adult subjects and 19 age-matched patients with histologically-confirmed cirrhosis and no clinical evidence encephalopathy. The latencies and amplitudes of evoked potentials and the alpha rhythm of the EEG were determined. In 6 of the 19 patients the latencies of P3a and/or P3b exceeded the corresponding mean for controls + 2 standard deviations of that mean. In 4 other patients the NCT was prolonged. In all of the patients the N200, VEPs and alpha rhythm of the EEG were normal. IN CONCLUSION: (i) Optimal isolation of ERPs is critically dependent on stimulus contrast and electrode placement; (ii) ERPs appear to be more sensitive than primary sensory evoked potentials or the EEG in detecting impaired brain neuroelectrophysiological function; and (iii) Cirrhotic patients without overt encephalopathy in whom P3a and/or P3b latencies are prolonged may have subclinical hepatic encephalopathy.

A gene for X-linked optic atrophy is closely linked to the Xp11.4-Xp11.2 region of the X chromosome.

The aim of this study was to identify the chromosomal location of the disease-causing gene in a family apparently segregating X-linked optic atrophy. A large family of 45 individuals with a four-generation history of X-linked optic atrophy was reexamined in a full ophthalmic as well as electrophysiological examination. A DNA linkage analysis of the family was undertaken in order to identify the chromosomal location of the disease-causing gene. Linkage analysis was performed with 26 markers that spanned the entire X chromosome. The affected males showed very early onset and slow progression of the disease. Ophthalmic study of the female carriers did not reveal any abnormalities. Close linkage without recombination was found at the MAOB locus (maximum LOD score [Zmax] 4.19). The Zmax - 1 support interval was found at a recombination fraction of .076 distal and .018 proximal to MAOB. Multipoint linkage analysis placed the optic atrophy-causing gene in the Xp11.4-p11.21 interval between markers DXS993 and DXS991, whereas any other localization along the X chromosome could be excluded.

Autosomal recessive retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium.

Retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium is a rare form of retinitis pigmentosa that starts early in life with preservation of retinal pigment epithelium adjacent to and under the retinal arterioles and that has hitherto been described as an isolated form. We examined 22 patients from one large family, together with two isolated patients, and confirmed the presumed autosomal recessive mode of inheritance in this type of retinitis pigmentosa. New findings associated with retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium were asteroid hyalosis in four (17%) of 24 patients, tortuosity of retinal arterioles in 11 (46%) of 24 patients, peripheral regions of opacified vessels in eight (33%) of 24 patients, and preservation not only of the para-arteriolar pigment epithelium, but also of the peripheral retinal pigment epithelium in 13 (54%) of 24 patients. Previously reported signs present in these patients were nystagmus in six (25%) of 24 patients, hypermetropia in 23 (96%) of 24 patients, optic nerve head drusen in nine (38%) of 24 patients, vascular sheathing in 11 (46%) of 24 patients, maculopathy in all 24 patients (100%), yellow round deposits in the posterior pole in nine (38%) of 24 patients, exudates resembling those in Coats' disease in two (8%) of 24 patients, visual field defects in all 24 patients (100%), and nondeductible electroretinograms in 21 (91%) of 23 patients. Linkage analysis carried out in the large family resulted in the assignment of a gene for retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium to chromosome 1q31-q32.1.

Thr4Lys rhodopsin mutation is associated with autosomal dominant retinitis pigmentosa of the cone-rod type in a small Dutch family.

A mother and daughter with autosomal dominant retinitis pigmentosa (adRP) were found to carry a cytosine-to-adenine transversion mutation at codon 4 of the rhodopsin gene. This mutation predicts a substitution of lysine for threonine at one of the glycosylation sites in the rhodopsin molecule (Thr4Lys). Both patients presented with a similar phenotype including a tigroid pattern of the posterior pole and a regional predilection for degenerative pigmentary changes in the inferior retina with corresponding visual field defects. The electroretinographic pattern was suggestive of RP of the cone-rod type. This report documents the clinical findings associated with this defined mutation of the rhodopsin gene.

Morphology and function of the corneal endothelium after long-term contact lens wear.

PURPOSE: To examine whether corneal hydration control is impaired in corneas with endothelial morphologic changes (increased variation in cell size and cell angularity) due to long-term low gas-permeable contact lens wear. METHODS: Twenty-one long-term wearers of low gas-permeable contact lenses (mean age, 41 years +/- 8 SD) and 18 age-matched controls (mean age, 42 years +/- 8 SD) were studied. To assess endothelial morphology, endothelial photographs were taken, enlarged 400X, scanned into a computer, and evaluated. Hydration control was assessed by a corneal stress test. Corneal swelling was induced by applying low gas-permeable soft contact lenses for 2 hours during eye closure. After the lenses were removed, the rate of deswelling was determined using optic pachometry. RESULTS: Morphologic analysis of the endothelial photographs showed a significant increase of polymegethism (P < 0.01) and pleomorphism (P < 0.01) in the group wearing contact lenses compared with the control group. The percentage of recovery of corneal thickness per hour (PRPH) from induced swelling proved to be significantly lower (P = 0.03) and the induced swelling proved to be significantly lower (P < 0.01) in the group wearing contact lenses than in the control group. Multiple regression analysis showed that the PRPH decreased as the morphologic alterations increased. However, this trend appeared not to be significant at the 5% level. A significant relationship was found between morphologic parameters and induced swelling, indicating that induced swelling decreased as the morphologic alterations increased. CONCLUSION: The results of this study indicate that increased endothelial polymegethism and pleomorphism may be accompanied by a decreased corneal hydration control in people who wear contact lenses.

The laplacian analysis of the pattern onset response in man.

The pattern onset VEP described by means of principal component analysis was shown to be composed of at least two overlapping time components, of which one has a striate and the other an extrastriate origin. This analysis was based on a multi (24)-electrode registration. We looked for a technique that can distinguish, with a limited number of electrodes, between the striate and extrastriate components and can be applied in the clinic. The calculation of a 5-point 'Laplacian' operator over the striate area enhances the contribution of the striate source relative to the contribution of the extrastriate source that lies outside the area of the operator, and vice versa. We applied two 5-point operators, one centered on Oz and the other 6 cm left of Oz. This montage allowed for the selective recording of the striate and extrastriate activities separately. This was proved by means of an adaptation paradigm that selectively reduced the striate contribution. Application of the laplacian operator for clinical practice is exemplified by means of the VEPs of a patient suspected of psychogenic hemianopsia.

Flicker electroretinograms: a systems analytic approach.

We observed multiple maxima and minima in the electroretinogram (ERG) first harmonics which varied as a function of adaptation level, mean illuminance, and modulation depth. Based on differences in response characteristics we identified a minimum of 3 parallel mechanisms operating at 3 frequency regions within the ERG: a low frequency region (less than 10 Hz), a midfrequency region (centered near 20 Hz), and a high frequency region (centered near 40 Hz). The low frequency region was observed both in dark- and light-adapted conditions, was basically linear, and showed nonlinear behavior only at high contrasts in either light or dark adaptation. It may be modeled as a low pass filter. The midfrequency region was clearly observed only above cone threshold, was nonlinear at low contrasts, and may be modeled as a linear filter followed by an essential nonlinearity. The high frequency region was observed under high levels of light adaptation and also was nonlinear at low contrast. It may be modeled also as a linear filter followed by an essential nonlinearity.

Visual evoked potential estimation of visual activity with a Laplacian derivation.

Visual acuity was estimated with visual evoked potentials in 13 healthy subjects. A Laplacian derivation of 5 electrodes was used to improve the signal-to-noise ratio and to enhance striate cortical activity selectively. In 6 subjects, the Laplacian derivation gave a more reliable estimation of visual acuity than did a single midline derivation. In the other 7 subjects, the quality of both estimations was comparable.

The application of Laplacian analysis in the recording of half-field pattern-onset evoked potentials.

The Laplacian operator in electroencephalographic measurements consists of a mathematical combination of the responses from a number of electrodes (e.g., five in a crosswise montage). It enhances activity from sources lying underneath the area covered, relative to activity from outside this area. Thus, by appropriate positioning, the contributions of extrastriate and striate sources can be recorded selectively. To quantify the contribution of each hemisphere to half-field onset evoked potentials, the responses in two Laplacian operators, one over each hemisphere, were analyzed and compared to monopolar derivations and a bipolar derivation between the two hemispheres. Both the Laplacian and bipolar analyses were helpful in interpretation of the responses.

Analysis of the electroretinogram in toxoplasma retinochorioiditis.

The decision to use therapy in toxoplasma retinochorioiditis depends on the location of the active lesion and the presence of vitreous activity. In eyes with dense vitreous clouding it can be difficult to see whether the macular region is involved or not. In theory the localisation of a lesion can be estimated on the basis of the flash ERG. The standard flash electroretinogram was recorded in 23 patients with inactive toxoplasma retinochorioiditis lesions in the retina. In 17 cases a lesion was present within the central 12 degrees of the visual field, 8 of these had a reduced photopic ERG. In 15 patients lesions were found outside the central 12 degrees, in 8 of whom the scotopic ERG was reduced. We conclude that the ERG can be of use in indicating the scar location in patients with dense vitreous clouding.

The electrooculogram: a refinement of the method.

The measurement of the light rise of the corneoretinal potential in the clinical routine depends critically on the constancy of the eye movements made by the subject. To verify to what extent the variability of the Arden ratio can be explained by the variability of these eye movements, an infrared scleral reflection technique was applied in order to monitor eye position and electrooculogram simultaneously. The data obtained in 10 normal subjects show that not only is the variability reduced substantially by correction for the actual eye movement, but also the routine procedure gives a systematic underestimation of the ratio. Monitoring eye movements makes available the use of eye movements of arbitrary size (e.g., optokinetic nystagmus), allowing for application of the method in uncooperative subjects such as children.

On the origin of the presaccadic spike potential.

The spike potential (SP) accompanying the onset of saccadic eye movements has been reported to originate near the orbital region. Its dependence on saccade size, however, does not correlate with the behaviour of any of the possible sources of the potential available in the orbital region. The exact size dependence cannot be studied from results obtained with classical ENG methods to detect the saccadic onset and furthermore without removal of the artefact in the signal caused by the corneo-retinal potential. We recorded the SP by monitoring the eye movements with an infrared scleral reflection method (IRIS), and carefully studied the SP amplitude as a function of saccade size, and revealed a more realistic function. Furthermore, removal of the artefact of the corneo-retinal potential revealed a biphasic wave shape of the SP instead of the usually observed monophasic peak. These results support the hypothesis that this electrical activity accompanying the onset of saccadic eye movements originates in the oculomotor neurones innervating the ocular muscle units.

Are eye movement evoked potentials different from pattern reversal evoked potentials?

The averaged lambda wave elicited by saccadic eye movements across a checkerboard pattern has been reported to differ from checkerboard reversal evoked responses, even when the electroencephalographic responses were corrected for the artefact caused by the movement of the dipole moment of the eye itself. Because of these differences it was suggested that the recording of the lambda wave might provide extra information in pathological circumstances. We performed experiments in which the parameters of the pattern (high contrast checkerboard pattern, 20' checks, large field 72 x 72 degrees) shift across the retina were carefully adjusted. For instance, eye movements were made across an integer and odd number of checks in order to mimic the pattern reversal. Furthermore, the timing of the pattern movement in the pattern reversal condition was adjusted so as to simulate the saccadic eye movement. The results seem to suggest that the reported dissimilarities between pattern reversal and eye movement evoked responses can be accounted for by the small differences of the retinal shift in the two conditions.

Pattern ERG and glaucomatous visual field defects.

In the past five years numerous reports have suggested that ganglion cell function can be tested by means of a specialized form of electroretinography, the so-called pattern electroretinogram (PERG). Because of the important potentials of a ganglion cell test for clinical use this technique has been applied by several investigators to patients with (presumed) ganglion cell dysfunction, especially glaucoma. On grounds of principle we had reason to question whether the reported positive results should be attributed to ganglion cell dysfunction or to other factors such as optical disturbances. We investigated in this study the PERG as a function of visual field loss in glaucoma patients with careful control of optical factors. We did not find changes in PERG as a function of field loss. So either field loss is not related to the mass behaviour of ganglion cells, or ganglion cells are not the prime basis of the PERG. We believe the latter to be true.