Assessment of Retinal Structural and Functional Characteristics in Eyes with Autoimmune Retinopathy.

PURPOSE: To evaluate the thicknesses of individual retinal layers, and the correlation between structural changes and functional loss using spectral domain optical coherence tomography (SD-OCT) scans and electroretinograms (ERG), in eyes with autoimmune retinopathy (AIR). METHODS: SD-OCT raster scans of 12 eyes from 6 patients serologically diagnosed with AIR were evaluated. Retinal layers were segmented along a 5 mm horizontal scan passing through the fovea. Retinal layers analyzed include full retinal thickness (FRT), retinal pigment epithelium and Bruch's membrane complex (RPE+BM complex), photoreceptor layer (PRL), inner nuclear layer (INL), combined ganglion cell and inner plexiform layers (GCL+), nerve fiber layer (NFL), and combined GCL+ and NFL layers (GCL+/NFL). Changes in the thicknesses of the layers were assessed in 0.5 mm increments along the B-scan in the central, nasal, and temporal regions. These recorded values were compared to corresponding values of 51 eyes from 51 subjects with no known ocular pathology. Full-field ERGs were obtained at corresponding visits and were interpreted by a grader masked to the diagnoses and OCT findings. RESULTS: The mean age of the patients was 59.5 years (range, 33-83), with 4 males (66.6%). Within the control population of 51 subjects, mean age was 51.5 years (range, 40-75), with 25 males (49%). Eyes with AIR showed a loss of retinal tissue compared to eyes with no known ocular pathology at the fovea. Specifically, the FRT, RPE+BM complex, and PRL exhibited thinning of statistically significance. ERG findings demonstrated a functional deficit which showed a good correlation with structural loss. Fifty (50) percent of eyes experienced central photoreceptor (rod and cone) dysfunction and 75% of eyes displayed peripheral photoreceptor (rod and cone) dysfunction. CONCLUSIONS: Eyes with AIR show a loss of retinal tissue compared to eyes with no known ocular pathology. The greatest loss appears to occur in the RPE and PRL. ERG findings correlate strongly with the loss of tissue seen in these layers. Thus, therapeutic options may be targeted to preserve these regions of the retina.

Asymmetry quantification utilizing hand radiographs.

Asymmetry can be either directional or fluctuating. Detection of abnormal amounts of asymmetry has important implications for clinical diagnosis, but measurement of subtle levels is very difficult. We describe a method and normative values for asymmetry quantification using hand radiographs.

CAMPS: computer-automated metacarpophalangeal profile system.

The metacarpophalangeal profile (MCP) pattern has been proven useful in describing individuals with genetic and nongenetic syndromes. However, the measurement of the 19 bone lengths is a tedious procedure requiring use of hand vernier calipers, detailed normative data to be looked up in extensive tables, hand calculator, and manual graphing techniques. Presently there are no reports of microcomputer-automated systems for the accurate measurement, recording, analysis, and graphing of MCP profiles. We describe a computer-automated metacarpophalangeal profile system (CAMPS) that will assist in the derivation of the MCP profile. This program allows the user to select different program routines that perform the functions necessary for MCP profile construction. The "data acquisition module" (DAM) assists in bone length measurement from contact prints of hand radiographs and stores the 19 measurements on a floppy disk. The "standardization analysis module" (SAM) then compares the 19 measurements to age- and sex-matched normal data and converts the raw data to z-score values. The "Pearson product-moment correlation module" (PPM) generates a correlation coefficient describing the degree of similarity between the two hands measured and graphically illustrates the resulting scatterplot. The "MCP plotting module" (MCPM) provides a graphic plot of the 19 bones in either transverse rows or phalangeal rays on a dot-matrix printer or X-Y plotter.

An electroretinal and visual evoked potential study in Friedreich's ataxia.

We made an electroretinographic (ERG) and visual evoked potential (VEP) study of 12 patients with Friedreich's ataxia whose diagnosis was established using the Quebec diagnostic criteria. ERGs and VEPs were elicited to the same stimulating conditions. Flash evoked luminance changes and pattern-specific evoked potentials to check and diamond stimuli were used. Statistical analysis of the data was made using independent sample t-tests. Significant VEP delays were present under all test conditions. The presence of significant interocular and interhemispheric delays as well as evidence of abnormal temporal dispersion of the VEP response suggest there to be both diffuse anterior visual system disease and retrochiasmal involvement in Friedreich's ataxia. The implicit times of the ERG b-waves were statistically within normal limits but the waveforms were of low amplitude and deformed and there were significant interocular implicit time differences. These ERG results suggest there are retinal conduction abnormalities in Friedreich's ataxia which possibly play a role in the genesis of the abnormal VEPs.

Multiple regression analysis of diagnostic predictors in optic nerve disease.

Demyelination is assumed to be the cause of the majority of cases of isolated optic neuritis. Because of the importance of establishing the presence of optic nerve dysfunction in patients suspected of having multiple sclerosis several new indices of optic nerve conduction have been reported including the visual evoked potential, the edge-light pupil cycle time, and the Pulfrich test. These measures purport to detect optic nerve dysfunction but with varying degrees of success. This study of 93 patients with clearly documented previous optic neuritis was conducted to determine the statistical relationship between these three measures and other clinical diagnostic indices for detection for previous optic nerve disease and the utility of the diagnostic predictors taken individually, and in combination. The other indices used were the presence of detectable optic atrophy, color vision defect and the presence of a relative afferent pupillary defect. The variables were submitted to linear stepwise multiple regression analysis which indicated that the presence of optic atrophy, defective color vision and prolonged pupil cycle time when used in combination provided the most useful diagnostic prediction of previous optic neuritis in this group of patients. The addition of visual evoked potentials, the Pulfrich test or presence of a relative afferent pupillary defect did not significantly increase predictive reliability.

Abnormal electroretinograms and visual evoked potentials in chronic papilledema using time-difference analysis.

Visual function is usually considered to be normal in papilledema. We report previously undescribed abnormalities in the electroretinograms (ERG) and visual evoked potentials (VEP) of two patients with chronic papilledema. The steady-state latencies of the ERG and VEP were calculated using time-difference analysis. The ERG was abnormal under both scotopic (slow) and photopic (fast) flicker conditions, but the VEP was abnormal only to fast flicker photopic stimulation. This may indicate a relative vulnerability of a high frequency signal system under conditions of raised intracranial pressure. The abnormalities resolved rapidly once the intracranial pressure had been normalised. The cause of the VEP and particularly the ERG abnormalities remains unknown.

The pattern electroretinogram in optic nerve demyelination.

The pattern electroretinogram (PERG) is probably generated by the ganglion cell layer of the retina whose axons constitute the conductive fibres of the optic nerves. A study was undertaken of the PERG in a group of patients with clinically definite multiple sclerosis who had suffered optic nerve demyelination to assess the value of recording the PERG as a method for electrophysiological determination of optic nerve dysfunction. Pattern visual evoked potentials (PVEP) were simultaneously recorded, each eye being stimulated separately, and four different check sizes were used. Although individual patients showed PERG abnormalities the results as a group showed no significant difference from the normal population so far as latency or amplitude of the PERG was concerned. Thus we conclude that the PERG, while an interesting measurement, does not satisfactorily reflect optic nerve dysfunction. Further, our results indicate that it is not such a useful measure as the pattern visual evoked response for detecting optic nerve disease.

Flash electroretinogram abnormalities in patients with clinically definite multiple sclerosis.

We studied the flash electroretinograms (ERGs) of 105 patients with multiple sclerosis who were divided into four groups. The first group had no history or clinical evidence of optic nerve dysfunction, the second and third groups had either left or right optic nerve disease respectively, and the fourth group had historical or clinical evidence of bilateral optic nerve disease. Statistical analysis of the data using analysis of variance (ANOVA) showed that the group of patients with no history or clinical evidence of optic nerve disease had no significant difference from the control group for their peak b-wave implicit times but the other three groups were significantly delayed on the affected side(s). Using the Mann-Whitney U-test we found all four patient groups had significantly greater absolute interocular latency differences from the control group. The electroretinal contribution to flash VEP delay was also investigated. In those patients with unilateral or bilateral optic nerve disease we found that in 14-31% of those patients with flash VEP delay there was also abnormal prolongation of the ERG b-wave. These results confirm a high incidence of retinal dysfunction in multiple sclerosis patients and may suggest that transynaptic degeneration of retinal structures occurs in optic nerve demyelination. The significant absolute interocular latency difference in particular may provide another electrophysiological parameter to establish a diagnosis of multiple sclerosis in suspect cases.

Orientation-specific visual evoked potential deficits in multiple sclerosis.

Checkerboard pattern reversal visual evoked potentials (VEPs) have proved useful in the confirmation of optic nerve disease in patients with multiple sclerosis (MS). Recently evidence of orientation-specific loss in contrast sensitivity and the presence of orientation-specific visual evoked potential (VEP) deficits in MS patients has been obtained using sinusoidal gratings as stimuli. This study reports the presence of orientation-specific VEP delay in MS using the conventional checkerboard pattern presented in two orientations: normally oriented (check condition) or diagonally oriented (diamond condition). Peak latency values of the N70 and P100 components of the VEP were statistically analyzed using appropriate ANOVA and nonparametric statistics. As a group of MS patients showed significant VEP delays under check and diamond pattern conditions. However, individual subject analysis revealed that about 20% of the MS population show VEP delay to only one pattern orientation. It was shown that by including a diamond pattern condition the diagnostic yield of VEP delay in these clinically definite MS patients was increased 11% over that obtained with check stimulation alone.

Giant axonal neuropathy: visual and oculomotor deficits.

Giant axonal neuropathy, a generalised disorder or neurofilaments, presents as a chronic, progressive peripheral neuropathy in childhood. Evidence for central nervous system involvement is demonstrated in this study of four male patients with giant axonal neuropathy who had defective visual function and abnormal ocular motility. The visual system was studied by electroretinography, which showed normal retinal function, and by visual evoked potentials, which showed disease of both optic nerves and retrochiasmal visual pathways. The ocular motility disorder, studied by electrooculography, comprised defective pursuit, inability to maintain eccentric gaze with gaze paretic and rebound nystagmus, abnormal optokinetic responses and failure of suppression of the vestibulo-ocular reflex by fixation. These findings suggested involvement by giant axonal neuropathy of the cerebellar and brain stem pathways important in the control of ocular motility.

Visual and auditory evoked potential correlates of cerebral malformations.

To date there are no systematic studies of the evoked potential correlates of cerebral malformations. A total of 109 sensory evoked potential studies (20 ERGs, 61 VEPs and 28 ABRs) were performed in 27 children with defined cerebral malformations. Diagnoses were confirmed by CT scan, supplemented by MRI, cranial ultrasound, or neuropathological examination. Sensory evoked potential studies were abnormal in over half of patients studied, but the VEP was unable to identify or distinguish specific supratentorial cerebral malformations. ABR abnormalities were documented in cases of holoprosencephaly, lissencephaly, pachygyria and generalized megalencephaly. ABR abnormalities were not observed in septo-optic dysplasia or focal dysplasia of the cerebral cortex. We conclude that evoked potentials are not a diagnostic criterion of severe dysplasias, but rather serve as a supplementary tool for detecting the variable associated abnormalities of brain development that may affect visual and central auditory pathways or their cerebral cortical or brainstem targets.

Pattern ergs and check size: absence of spatial frequency tuning.

The pattern electroretinogram (PERG), whose genesis appears to depend upon intact retinal ganglion cells, is receiving attention from clinical electrophysiologists because of its possible value as an aid in the diagnosis of optic nerve disease. Until now there have been no published studies describing the PERG in a large normal population nor has the effect of check size been systematically investigated in normals. We have investigated peak latency, amplitude and interocular amplitude ratio of the P, Q and R-waves of the PERG and their relationship to several pattern visual evoked potential (PVEP) parameters. In 35 normal subjects simultaneous PERGs and PVEPs were recorded using four different check sizes. The study of these small amplitude waveforms was facilitated by digital subtraction of eye movement artefact. The distribution of normal control data is described and a clinical terminology for the PERG components is proposed.

Abnormal pattern electroretinograms with macular cherry-red spots: evidence for selective ganglion cell damage.

A macular cherry red spot is a strikingly visible abnormality indicating storage of an abnormal metabolic product by the retinal ganglion cells. The flash and pattern electroretinograms (ERG) and visual evoked potentials (VEP) of a patient with the cherry-red spot-myoclonus syndrome, a sialidosis due to neuraminidase deficiency, were studied. The flash ERG was normal but the pattern ERG had an abnormal waveform with a significantly attenuated p-q wave component. Corresponding flash VEPs were normal, but pattern VEPs were delayed. This case documents human evidence that the pattern ERG is organised in the ganglion cells whereas the flash ERG, as is well known, is generated in the distal retina.

Assessment of cisplatin-induced ototoxicity using derived-band ABRs.

Ototoxicity is an adverse side effect of numerous therapeutic agents (amino-glycoside antibiotics, blood chelating agents, diuretics and oncologic drugs) used in treatment of both adult and pediatric patients. Recently, there has been increasing interest in using the auditory brainstem response (ABR) to detect both short-term effects of ototoxicity in adults and long-term effects of drug administration on neonates and children. Since click ABRs have relatively poor frequency selectivity they best approximate the pure-tone hearing threshold in the 2000-4000 Hz frequency range. Hearing loss above or below that frequency range can be present without producing significant abnormalities in the ABR waveform parameters. Frequency-specific ABRs can be obtained using the derived response technique. The purpose of this study was to investigate early cisplatin ototoxicity using both the broadband click and derived ABR and to monitor progressive hearing loss with repeated drug trials in 18 patients studied over a 2-year period. ABRs were obtained serially prior to and following intravenous administration of cisplatin. Derived ABRs were found to be more sensitive than broadband click ABR in detecting early high-frequency hearing loss. For click ABRs, the cumulative dosage of cisplatin at age of ABR examination was correlated with hearing loss in only those patients under 3 years of age. No significant correlation was found between cumulative cisplatin dosage when tested and degree of hearing loss in those patients over 3 years of age.

Frequency dependent maturation of the cochlea and brainstem evoked potentials.

The anatomical development of the human cochlea starts in the middle basal turn and progresses both toward the base and the apex. Behavioral responses, in contrast, appear to emerge for lower frequencies first. Cochlear tuning may continue to change during early development and so effect electrophysiological and behavioral measures of maturation. The maturation of the cochlear traveling wave delay as well as the ABR I-V interval was investigated using the derived response technique which permits a frequency dependent analysis of this maturation. It was found that the traveling wave delay decreased significantly with age for the most basal part of the cochlea; however, it was not affected by age for more apical locations. The I-V delay difference with the adult values was found significantly shorter in the derived octave band with CF = 2.8 kHz than in all other bands for the preterm, term and infant groups. This suggests that the frequency dependent electrophysiological maturation of the brainstem parallels the anatomical development of the cochlea.

Improved contrast sensitivity with antireflective coated lenses in the presence of glare.

Contrast sensitivity was measured to quantify the glare-reducing effects of antireflective coatings of magnesium fluoride on spectacle lenses. Experiments were conducted on four subjects, who judged contrast thresholds while wearing corrective spectacles with noncoated and then coated lenses in both the absence and the presence of a source of glare (back-scattered reflection from the posterior surface of their lenses). Glare substantially reduced contrast sensitivity at all spatial frequencies; although the reduction was greater at higher spatial frequencies ther was no shift in peak contrast sensitivity. The coated lenses enhanced contrast sensitivity in the presence of glare between 1.5 and 5 times compared with the noncoated lenses. In the absence of glare, contrast sensitivity was greater with coated lenses than with noncoated lenses.

Increased visual field area with antireflective coated lenses in the presence of glare.

Visual fields were charted with the Goldmann perimeter for five subjects wearing corrective spectacles with noncoated lenses and then lenses with antireflective coatings of mmagnesium fluoride in both the absence and the presence of a source of glare (back-scattered reflection from the posterior surface of their lenses). There was a greater reduction in temporal isopters than nasal isopters in the presence of glare with both types of lenses, but the coated lenses were superior to the noncoated lenses in reducing the effect of glare on the visual field area.

Variable expressivity in X-linked congenital stationary night blindness.

X-linked congenital stationary night blindness (CSNB) is a well-documented disorder in which the most striking clinical features are impaired night vision, nystagmus and myopia. Recent reports have highlighted differing features between families, and it has been suggested that these discrepancies may be the result of two loci on the X chromosome or of two mutant alleles. We outline the clinical and visual function findings in 42 affected members from 10 families and 1 adopted person. There was a relative unawareness of the disorder in clinical practice. At least one of the main features of CSNB was absent in 75% of the patients. The visual function values varied widely, both between and within families (visual acuity 20/30 to 20/400, refractive error +1.50 to -22.50 and rod segment elevation 1.5 to 3.0 log units). The findings are consistent with a single allele exhibiting a wide variation in clinical expression.

Sialidosis: the cherry-red spot--myoclonus syndrome.

The sialidoses are a group of storage disorders of autosomal recessive inheritance in which there is a deficiency of lysosomal neuraminidase (sialidase) activity and associated sialyloligosacchariduria. Patients with one type of sialidosis may present initially to the ophthalmologist because of a cherry-red spot at the macula. In most of these patients progressive neurologic deficits ultimately develop; myoclonus is a prominent feature. A patient with the so-called cherry-red spot--myoclonus syndrome is described who had a marked deficit of the ocular smooth pursuit system, with consequent nystagmus. His visual system was normal clinically and electrophysiologically despite the obvious storage in the retinal ganglion cells.

Impairment of ocular blood flow during regional orbital anesthesia.

BACKGROUND: Regional anesthesia for ophthalmic surgery has been associated with ischemic complications, such as central retinal vascular occlusion, optic atrophy and ischemic optic neuropathy. Impairment of pulsatile ocular blood flow (POBF) may occur with regional orbital anesthesia. In this study we quantified POBF in patients undergoing regional orbital anesthesia. METHODS: Eleven patients (12 eyes) with a mean age of 76.5 years having regional orbital anesthesia for cataract or retinal surgery at a private refractive surgical centre in Calgary had POBF monitoring before, during and 15 minutes after induction of anesthesia. RESULTS: There were no significant changes in intraocular pressure or heart rate during the induction phase or 15 minutes after induction of regional orbital anesthesia. However, ocular blood flow indices, including pulse amplitude, pulse volume and POBF, were significantly reduced following attainment of regional orbital blockade (p < 0.05). With time there was recovery in these variables, but they all remained significantly reduced from baseline 15 minutes later. INTERPRETATION: Ocular blood flow appears to be significantly impaired during regional orbital anesthesia, induced as described. There could be benefit in monitoring POBF to reveal otherwise undetectable deleterious effects on retinal circulation in patients having retrobulbar injections, orbital compression or digital manipulation of the globe.