Use of pattern electroretinography to differentiate acute optic neuritis from acute anterior ischemic optic neuropathy

The transient pattern electroretinogram (PERG) was recorded from 16 patients with acute neuritis and from 13 patients with acute non-arteritic ischemic optic neuropathy (AION). All patients were tested within 35 days from the the onset of visual symptoms and all had significant central visual field abnormalities in their affected eyes as quantified by automated perimetry. Analysis of the PERGs showed that the amplitude of the N95 peak was abnormally reduced for each eye affected with AION while it remained normal in optic neuritis. No significant alteration in P50 amplitude was observed in either condition. The loss of N95 amplitude in AION was highly correlated with the average depth of visual field loss (in decibels) within a radius of 10° of fixation. These results suggest that PERG could be used early in the course of optic neuropathy to distinguish optic neuritis from AION in those cases for which the diagnosis is still uncertain after the clinical examination.     

The electroretinogram in multiple sclerosis and demyelinating optic neuritis

The electroretinogram (ERG) to flashes of white light presented under photopic conditions and the pattern reversal visual evoked potentials (PR-VEPs) from both eyes were recorded from 14 patients with multiple sclerosis (MS) with monocular demyelinating optic neuritis (DON) and from 11 patients soon after presenting with monocular demyelinating optic neuritis alone. Fifteen and 10 normal subjects, matched for age and sex, were used as controls for each group of patients respectively. In the DON group of patients and controls the flicker following ERG (FF-ERG) to white flashes of light at 40 Hz was also recorded. Skin electrodes and averaging procedures were used for all the recordings. The PR-VEP elicited with stimulation of the affected eye was absent or abnormally delayed, and the amplitude of the ‘b’ wave of ERG of the affected eye was diminished in all patients. The ‘b’ wave latency, however, was similar in both affected and non-affected eyes and the controls. There was no difference in ‘a’ wave amplitude and latency between eyes of patients and normal subjects. The FF-ERG in 8 out of 10 patients with satisfactory recordings was diminished in the affected eye. These results provide neurophysiological evidence that retinal damage is not due to loss of myelin but is an early feature of demyelinating optic neuritis. This damage preferentially affects the retinal elements associated with the generation of the ‘b’ wave of the ERG, probably the glial cells of Müller.     

Pattern ERG: effects of reference electrode site,stimulus mode and check size

We studied monocular pattern ERG (PERG) in 10 normal subjects and a patient with optic neuritis. No clinically significant PERG could be recorded from the occluded eye with any reference (ipsilateral ear or temple, or midfrontal), indicating that cross-contamination is not present with binocular testing. Ipsilateral temple reference minimized VEP (P100/N100) contribution to the PERG N95 which occurred with ipsilateral ear or midfrontal reference. The conclusions were confirmed by results from the patient, who had marked monocular delay of a normal amplitude P100. Twenty-four subjects were tested with monocular and binocular stimulation using an ipsilateral temple reference. There were differences in PERG latencies and amplitudes although the interside amplitude ratio showed smaller differences with binocular stimulation. Increasing check size (17, 35 and 70 min) decreased P50 and N95 latencies and increased P50 amplitude.     

Retinal Nerve Fibre Layer Thinning in Patients with Clinically Isolated Optic Neuritis and Early Treatment with Interferon-Beta

Background

Optic neuritis is associated with neurodegeneration leading to chronic impairment of visual functions.

Objective

This study investigated whether early treatment with interferon beta (IFN-β) slows retinal nerve fibre layer (RNFL) thinning in clinically isolated optic neuritis.

Methods

Twenty patients with optic neuritis and visual acuity decreased to ≤0.5 (decimal system) were included into this prospective, open-label, parallel group 4-month observation. After methylprednisolone pulse therapy, 10 patients received IFN-β from week 2 onwards. This group was compared to 10 patients free of any disease modifying treatment (DMT). The parameter of interest was change in RNFL thickness assessed at baseline and at weeks 4, 8, and 16. Changes in visual acuity, visual field, and visual evoked potentials (VEPs) served as additional outcome parameters.

Results

RNFL thinning did not differ between the groups with a mean reduction of 9.80±2.80 µm in IFN-β-treated patients (±SD) vs. 12.44±5.79 µm in patients who did not receive DMT (baseline non-affected eye minus affected eye at week 16; p = 0.67, t-test, 95% confidence interval: −15.77 to 10.48). Parameters of visual function did not show any differences between the groups either.

Conclusions

In isolated optic neuritis, early IFN-β treatment did not influence RNFL thinning nor had it any effect on recovery of visual functions.     

Therapeutic benefit of radial optic neurotomy in a rat model of glaucoma

Radial optic neurotomy (RON) has been proposed as a surgical treatment to alleviate the neurovascular compression and to improve the venous outflow in patients with central retinal vein occlusion. Glaucoma is characterized by specific visual field defects due to the loss of retinal ganglion cells and damage to the optic nerve head (ONH). One of the clinical hallmarks of glaucomatous neuropathy is the excavation of the ONH. The aim of this work was to analyze the effect of RON in an experimental model of glaucoma in rats induced by intracameral injections of chondroitin sulfate (CS). For this purpose, Wistar rats were bilaterally injected with vehicle or CS in the eye anterior chamber, once a week, for 10 weeks. At 3 or 6 weeks of a treatment with vehicle or CS, RON was performed by a single incision in the edge of the neuro-retinal ring at the nasal hemisphere of the optic disk in one eye, while the contralateral eye was submitted to a sham procedure. Electroretinograms (ERGs) were registered under scotopic conditions and visual evoked potentials (VEPs) were registered with skull-implanted electrodes. Retinal and optic nerve morphology was examined by optical microscopy. RON did not affect the ocular hypertension induced by CS. In eyes injected with CS, a significant decrease of retinal (ERG a- and b-wave amplitude) and visual pathway (VEP N2-P2 component amplitude) function was observed, whereas RON reduced these functional alterations in hypertensive eyes. Moreover, a significant loss of cells in the ganglion cell layer, and Thy-1-, NeuN- and Brn3a- positive cells was observed in eyes injected with CS, whereas RON significantly preserved these parameters. In addition, RON preserved the optic nerve structure in eyes with chronic ocular hypertension. These results indicate that RON reduces functional and histological alterations induced by experimental chronic ocular hypertension.     

New actors in optic neuritis pathogenesis

The aim of the present report was to analyze the involvement of glutamate neurotoxicity in retinal ganglion cell loss and optic nerve damage induced by experimental optic neuritis. For this purpose, the authors used an optic neuritis model induced by immunisation with myelin oligodendrocyte glycoprotein (AON). The authors describe a correlation in the timing of retinal ganglion cell (RGC) loss with alterations in the optic nerve actin cytoskeleton dynamic, and visual dysfunction. In addition, they show that an intravitreal injection of glutamate mimics, and an NMDA receptor antagonist avoids the effect of pre-clinical AON on visual functions and RGC number, as well as on optic nerve actin cytoskeleton. Taken together, their results support that avoiding glutamate neurotoxicity could become a new therapeutic approach for optic neuritis treatment.

     

The origin of the electroretinogram induced by structured stimuli in man

The Authors studied the checkerboard pattern electroretinogram (PERG) behaviour in normal subjects and in patients suffering from traumatic lesion of optic nerve, demyelinating optic neuritis, axonal optic neuritis, retinal vascular disorders and retinitis pigmentosa in order to verify the PERG origin. According to our data the PERG appears to originate from ganglion cells since the signal diminished or disappeared in axonal lesion of optic nerve, as a result of retrograde ganglion cell degeneration. Furthermore, the demyelinating lesions of optic nerve were not able to modify the PERG wave. In patients suffering from retinal receptor disturbances the flash electroretinogram (FERG), which is probably an expression of receptor activity, was greatly impaired, whereas PERGs were either normal or less impaired than FERGs. These data demonstrate the different origin of PERG and FERG.     

Bilateral optic neuritis in a child following Epstein-Barr virus infection

A rare case of bilateral optic neuritis is presented in a child with no light perception. Ophthalmic examination revealed dilated pupils without reaction to the light, swollen optic discs with small peripapillary hemorrhages in both eyes. Serology revealed evidence of recent Epstein-Barr virus infection. After treatment with high dose of corticosteroid visual acuity gradually improved. After four months visual acuity was normal despite complete pallor of the optic disc. Ebstein-Barr virus infection should be considered in the differential diagnosis of bilateral optic neuritis in a child with severe bilateral visual loss.     

Optic Nerve Diffusion Tensor Imaging after Acute Optic Neuritis Predicts Axonal and Visual Outcomes

Background

Early markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS).

Objectives

To assess whether early measurement of diffusion tensor imaging (DTI) parameters (axial and radial diffusivity) within the optic nerve during and after acute demyelinating optic neuritis (ON) could predict axonal (retinal nerve fibre layer thinning and multi-focal visual evoked potential amplitude reduction) or clinical (visual acuity and visual field loss) outcomes at 6 or 12 months.

Methods

Thirty-seven patients presenting with acute, unilateral ON were studied at baseline, one, three, six and 12 months using optic nerve DTI, clinical and paraclinical markers of axonal injury and clinical visual dysfunction.

Results

Affected nerve axial diffusivity (AD) was reduced at baseline, 1 and 3 months. Reduced 1-month AD correlated with retinal nerve fibre layer (RNFL) thinning at 6 (R=0.38, p=0.04) and 12 months (R=0.437, p=0.008) and VEP amplitude loss at 6 (R=0.414, p=0.019) and 12 months (R=0.484, p=0.003). AD reduction at three months correlated with high contrast visual acuity at 6 (ρ = -0.519, p = 0.001) and 12 months (ρ = -0.414, p=0.011). The time-course for AD reduction for each patient was modelled using a quadratic regression. AD normalised after a median of 18 weeks and longer normalisation times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months. Affected nerve radial diffusivity (RD) was unchanged until three months, after which time it remained elevated.

Conclusions

These results demonstrate that AD reduces during acute ON. One month AD reduction correlates with the extent of axonal loss and persistent AD reduction at 3 months predicts poorer visual outcomes. This suggests that acute ON therapies that normalise optic nerve AD by 3 months could also promote axon survival and improve visual outcomes.     

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

Multiple sclerosis is an immune-mediated, demyelinating and neurodegenerative disease that currently lacks any neuroprotective treatments. Innovative neuroprotective trial designs are required to hasten the translational process of drug development. An ideal target to monitor the efficacy of strategies aimed at treating multiple sclerosis is the visual system, which is the most accessible part of the human central nervous system. A novel C57BL/6 mouse line was generated that expressed transgenes for a myelin oligodendrocyte glycoprotein-specific T cell receptor and a retinal ganglion cell restricted-Thy1 promoter-controlled cyan fluorescent protein. This model develops spontaneous or induced optic neuritis, in the absence of paralytic disease normally associated with most rodent autoimmune models of multiple sclerosis. Demyelination and neurodegeneration could be monitored longitudinally in the living animal using electrophysiology, visual sensitivity, confocal scanning laser ophthalmoscopy and optical coherence tomography all of which are relevant to human trials. This model offers many advantages, from a 3Rs, economic and scientific perspective, over classical experimental autoimmune encephalomyelitis models that are associated with substantial suffering of animals. Optic neuritis in this model led to inflammatory damage of axons in the optic nerve and subsequent loss of retinal ganglion cells in the retina. This was inhibited by the systemic administration of a sodium channel blocker (oxcarbazepine) or intraocular treatment with siRNA targeting caspase-2. These novel approaches have relevance to the future treatment of neurodegeneration of MS, which has so far evaded treatment.     

Intravitreal Transplantation of Human Umbilical Cord Blood Stem Cells Protects Rats from Traumatic Optic Neuropathy

Objectives

To treat traumatic optic neuropathy (TON) with transplantation of human umbilical cord blood stem cells (hUCBSC) and explore how transplanted stem cells participate in the neuron repairing process.

Methods

A total of 195 Sprague-Dawley rats were randomly assigned to three groups: sham-surgery, optic nerve injury, and stem cell transplant group. Optic nerve injury was established in rats by directly clamping the optic nerve for 30 seconds. hUCBSC was microinjected into the vitreous cavity of injured rats. Optic nerve function was evaluated by flash visual evoked potentials (F-VEP). Apoptosis in retina tissues was detected by TUNEL staining. GRP78 and CHOP gene expression was measured by RT-PCR.

Results

After injury, transplantation of hUCBSC significantly blunted a reduction in optic nerve function indicated by smaller decreases in amplitude and smaller increases in peak latency of F-VEP waveform compared to the injury alone group. Also, significant more in retinal ganglion cell (RGC) count and less in RGC apoptosis were detected after transplantation compared to injured rats. The protective effect correlated with upregulated GRP78 and downregulated CHOP mRNA expression.

Conclusion

Intravitreal transplantation of hUCBSCs significantly blunted a reduction in optic nerve function through increasing RGC survival and decreasing retinal cell apoptosis. The protective role of transplantation was associated with upregulation of GRP78 expression and downregulation of CHOP expression in retinal cells.     

Baseline Magnetic Resonance Imaging of the Optic Nerve Provides Limited Predictive Information on Short-Term Recovery after Acute Optic Neuritis

Background

In acute optic neuritis, magnetic resonance imaging (MRI) may help to confirm the diagnosis as well as to exclude alternative diagnoses. Yet, little is known on the value of optic nerve imaging for predicting clinical symptoms or therapeutic outcome.

Purpose

To evaluate the benefit of optic nerve MRI for predicting response to appropriate therapy and recovery of visual acuity.

Methods

Clinical data as well as visual evoked potentials (VEP) and MRI results of 104 patients, who were treated at the Department of Neurology with clinically definite optic neuritis between December 2010 and September 2012 were retrospectively reviewed including a follow up within 14 days.

Results

Both length of the Gd enhancing lesion (r = -0.38; p = 0.001) and the T2 lesion (r = -0.25; p = 0.03) of the optic nerve in acute optic neuritis showed a medium correlation with visual acuity after treatment. Although visual acuity pre-treatment was little but nonsignificantly lower if Gd enhancement of the optic nerve was detected via orbital MRI, improvement of visual acuity after adequate therapy was significantly better (0.40 vs. 0.24; p = 0.04). Intraorbitally located Gd enhancing lesions were associated with worse visual improvement compared to canalicular, intracranial and chiasmal lesions (0.35 vs. 0.54; p = 0.02).

Conclusion

Orbital MRI is a broadly available, valuable tool for predicting the improvement of visual function. While the accurate individual prediction of long-term outcomes after appropriate therapy still remains difficult, lesion length of Gd enhancement and T2 lesion contribute to its prediction and a better short-term visual outcome may be associated with detection and localization of Gd enhancement along the optic nerve.     

Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey''s visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM.     

Inapparent visual field defects in multiple sclerosis patients

To assess inapparent visual field defects in patients with multiple sclerosis free from optic neuritis. During 5 years period 120 patients with multiple sclerosis were examined at the University Department of Ophthalmology, Zagreb University Hospital Center. They were divided into three groups with 40 patients each: patients with acute unilateral optic neuritis, referred to ophthalmologist and treated with pulsed steroid therapy; patients with subjective feeling of blurred vision, normal visual acuity and no signs of acute optic neuritis; and patients free from subjective signs of visual impairment. Study patients underwent standard ophthalmologic examination and visual field testing in photopia by use of quantitative kinetic Goldmann perimetry. The initial and control examination by visual field testing were performed at least 6 months apart. Study results showed 65% of multiple sclerosis patients to have visual field defects without subjective signs of impaired vision. The most common defects were mild to moderate visual field narrowing with blind spot enlargement and depression from above. The following results were recorded: acute optic neuritis group: normal in 13/40 (32.5%) for the affected eyes and 27/40 (67.5%) for fellow eyes; mild visual field narrowing in 4/40 (10%) for the affected eyes and 10/40 (25%) for fellow eyes; moderate visual field narrowing with blind spot enlargement in 14/40 (35%) for the affected eyes and 1/40 (2.5%) for fellow eyes; and paracentral and arcuate scotomata in 9/40 (22.5%) for the affected eyes and 2/40 (5%) for fellow eyes; subjective symptom group: normal in 8/40 (20%) for the affected eyes and 11/40 (27.5%) for fellow eyes; mild visual field narrowing in 11/40 (27.5%) for the affected eyes and 16/40 (40%) for fellow eyes; moderate visual field narrowing with blind spot enlargement in 18/40 (45%) for the affected eyes and 10/40 (25%); andparacentral and arcuate scotomata in 3/40 (7.5%) for both affected and fellow eyes; and subjective symptom-free group: normal in 24/80 (30%), mild visual field narrowing in 22/80 (27.5%) moderate visual field narrowing with blind spot enlargement in 24/80 (30%); and paracentral and arcuate scotomata in 10/80 (12.5%). The presence of subclinical form of optic nerve involvement could be demonstrated in a very early stage of multiple sclerosis by the introduction of visual field testing in the standard examination protocol.     

Rapid activity-dependent sprouting of optic fibers into a local area denervated by application of beta-bungarotoxin in goldfish tectum

The retinotectal projection is known to be capable of extensive long-term expansion of connections, but it is not known how fast such changes can occur or what triggers sprouting of terminals. We studied sprouting of optic fibers into an area denervated by local microinjection of beta-bungarotoxin (β-BTX), a specific presynaptic neurotoxin with phospholipase A₂ activity that destroys nerve terminals at the neuromuscular junction. After injection of 0.1 pmol of β-BTX, the optic terminals fired spontaneously with decreasing amplitude and became silent within 1 to 2 h. Outside the injection zone, the retinotectal map was normal, so the silent zone was associated with a scotoma in the visual field. Horseradish peroxidase (HRP) staining of the entire optic nerve showed a denervated region at the injection site with beaded, degenerating fibers at its edge. Between 3 and 9 days later, optic units were recorded within the injection zone whose receptive fields lay just outside the scotoma in the visual field, indicating that intact surrounding terminals had sprouted into the area. These sprouts made functional connections, as indicated by field potential recordings and current source-density analysis. At this time, HRP staining also demonstrated retinal innervation within the injection zone. By 12 days, normal maps with no scotoma were recorded and HRP staining was normal at the injection site, indicating that the β-BTX-damaged fibers had regenerated to reclaim their tectal sites. The results show that the retinotectal projection of goldfish is very dynamic, since intact optic fibers can sprout into adjacent vacant postsynaptic territory within 2 to 3 days, much faster than previously reported. In a final experiment, we showed that this sprouting is activity-dependent, since it could be prevented by blocking retinal activity with intraocular tetrodotoxin (TTX) during the first 2 days postinjection, even though TTX block of activity does not block regeneration in this system. One possible mechanism for this rapidly triggered sprouting is that arachidonic acid liberated by β-BTX acts as a sprouting factor to attract surrounding healthy fibers into the denervated region but requires activity at the terminals to be effective. © 1996 John Wiley & Sons, Inc.     

Self-motion-induced eye movements: effects on visual acuity and navigation

Self-motion disturbs the stability of retinal images by inducing optic flow. Objects of interest need to be fixated or tracked, yet these eye movements can infringe on the experienced retinal flow that is important for visual navigation. Separating the components of optic flow caused by an eye movement from those due to self-motion, as well as using optic flow for visual navigation while simultaneously maintaining visual acuity on near targets, represent key challenges for the visual system. Here we summarize recent advances in our understanding of how the visuomotor and vestibulomotor systems function and interact, given the complex task of compensating for instabilities of retinal images, which typically vary as a function of retinal location and differ for each eye.     

Ischemic tolerance protects the rat retina from glaucomatous damage

Glaucoma is a leading cause of acquired blindness which may involve an ischemic-like insult to retinal ganglion cells and optic nerve head. We investigated the effect of a weekly application of brief ischemia pulses (ischemic conditioning) on the rat retinal damage induced by experimental glaucoma. Glaucoma was induced by weekly injections of chondroitin sulfate (CS) in the rat eye anterior chamber. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 min; this maneuver started after 6 weekly injections of vehicle or CS and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. Glaucoma was evaluated in terms of: i) intraocular pressure (IOP), ii) retinal function (electroretinogram (ERG)), iii) visual pathway function (visual evoked potentials, (VEPs)) iv) histology of the retina and optic nerve head. Retinal thiobarbituric acid substances levels were assessed as an index of lipid peroxidation. Ischemic conditioning significantly preserved ERG, VEPs, as well as retinal and optic nerve head structure from glaucomatous damage, without changes in IOP. Moreover, ischemia pulses abrogated the increase in lipid peroxidation induced by experimental glaucoma. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in glaucoma treatment.     

Relationship between Optical Coherence Tomography and Electrophysiology of the Visual Pathway in Non-Optic Neuritis Eyes of Multiple Sclerosis Patients

Purpose

Loss of retinal ganglion cells in in non-optic neuritis eyes of Multiple Sclerosis patients (MS-NON) has recently been demonstrated. However, the pathological basis of this loss at present is not clear. Therefore, the aim of the current study was to investigate associations of clinical (high and low contrast visual acuity) and electrophysiological (electroretinogram and multifocal Visual Evoked Potentials) measures of the visual pathway with neuronal and axonal loss of RGC in order to better understand the nature of this loss.

Methods

Sixty-two patients with relapsing remitting multiple sclerosis with no previous history of optic neuritis in at least one eye were enrolled. All patients underwent a detailed ophthalmological examination in addition to low contrast visual acuity, Optical Coherence Tomography, full field electroretinogram (ERG) and multifocal visual evoked potentials (mfVEP).

Results

There was significant reduction of ganglion cell layer thickness, and total and temporal retinal nerve fibre layer (RNFL) thickness (p<0.0001, 0.002 and 0.0002 respectively). Multifocal VEP also demonstrated significant amplitude reduction and latency delay (p<0.0001 for both). Ganglion cell layer thickness, total and temporal RNFL thickness inversely correlated with mfVEP latency (r = −0.48, p<0.0001 respectively; r = −0.53, p<0.0001 and r = −0.59, p<0.0001 respectively). Ganglion cell layer thickness, total and temporal RNFL thickness also inversely correlated with the photopic b-wave latency (r = −0.35, p = 0.01; r = −0.33, p = 0.025; r = −0.36, p = 0.008 respectively). Multivariate linear regression model demonstrated that while both factors were significantly associated with RGC axonal and neuronal loss, the estimated predictive power of the posterior visual pathway damage was considerably larger compare to retinal dysfunction.

Conclusion

The results of our study demonstrated significant association of RGC axonal and neuronal loss in NON-eyes of MS patients with both retinal dysfunction and post-chiasmal damage of the visual pathway.     

Effect of spatial frequency on simultaneous recorded steady-state pattern electroretinograms and visual evoked potentials

Pattern electroretinograms (P-ERGs) and visual evoked potentials (VEPs) to 4 Hz alternating square-wave gratings were simultaneously recorded in 23 subjects. Responses were Fourier analyzed and amplitude and phase of the 2nd and 4th temporal harmonics were measured.The spatial frequency-amplitude function of the P-ERG 2nd harmonic component displayed either a bandpass tuning behavior, or a low-pass behavior. The peak amplitude for subjects with bandpass tuning was at 1.5 c/deg. The phase of the P-ERG 2nd harmonic decreased monotonically as spatial frequency increased. The VEP 2nd harmonic had a bimodal spatial frequency function with a peak at 3 c/deg and a second increase at spatial frequencies below 1 c/deg, regardless of the P-ERG characteristics. The phase of VEP 2nd and 4th harmonic had an inverted U-shaped function with peak at 3 c/deg and 1.5 c/deg respectively.Comparison of simultaneously recorded P-ERG and VEP spatial frequency functions demonstrated different tuning behavior for cortical and retinal responses. It is concluded that the proposed technique permits the separate analysis of retinal and cortical processing of visual information. The 2nd and 4th harmonic components of VEP behave independently of each other suggesting they may be generated by different subsystems.     

Metabolic changes in the visual cortex are linked to retinal nerve fiber layer thinning in multiple sclerosis

Objective

To investigate the damage to the retinal nerve fiber layer as part of the anterior visual pathway as well as an impairment of the neuronal and axonal integrity in the visual cortex as part of the posterior visual pathway with complementary neuroimaging techniques, and to correlate our results to patients'' clinical symptoms concerning the visual pathway.

Design, Subjects and Methods

Survey of 86 patients with relapsing-remitting multiple sclerosis that were subjected to retinal nerve fiber layer thickness (RNFLT) measurement by optical coherence tomography, to a routine MRI scan including the calculation of the brain parenchymal fraction (BPF), and to magnetic resonance spectroscopy at 3 tesla, quantifying N-acetyl aspartate (NAA) concentrations in the visual cortex and normal-appearing white matter.

Results

RNFLT correlated significantly with BPF and visual cortex NAA, but not with normal-appearing white matter NAA. This was connected with the patients'' history of a previous optic neuritis. In a combined model, both BPF and visual cortex NAA were independently associated with RNFLT.

Conclusions

Our data suggest the existence of functional pathway-specific damage patterns exceeding global neurodegeneration. They suggest a strong interrelationship between damage to the anterior and the posterior visual pathway.