Optic atrophy as a sign of wolfram syndrome.

BACKGROUND: The hallmark of Wolfram syndrome -- an extremely rare autosomal recessive disorder -- is the association of juvenile onset diabetes mellitus with optic atrophy. Additional symptoms such as deafness and diabetes insipidus may develop. HISTORY AND SIGNS: An 18-year-old man suffered progressive visual loss over the last seven years. Severe optic atrophy with extensive cupping and slightly elevated intraocular pressure in both eyes were found. Perimetry revealed peripheral defects with paracentral scotomas. ERG results excluded tapetoretinal degeneration; visual evoked responses were delayed. At the age of nine the patient had been diagnosed with diabetes mellitus type I and neurosensory deafness, seven years later a beginning hypogonadism was found. THERAPY AND OUTCOME: Wolfram syndrome is a progressive degenerative disorder with reduced life expectancy. Treatment is symptomatic. CONCLUSIONS: Wolfram syndrome should be considered in every patient who presents with optic atrophy and juvenile onset diabetes mellitus.

Cutaneous ulceration after injection of polyethylene-glycol-modified interferon alpha associated with visual disturbances in a melanoma patient.

Interferons are used in the therapy of multiple sclerosis, Kaposi's sarcoma, hepatitis and melanoma. Their short half-life that requires frequent injections can be increased by polyethylene glycol (PEG) modification. A 50-year-old patient was diagnosed as having an acrolentiginous melanoma (Breslow >5 mm, Clark level IV) and inguinal lymph node metastases. After surgical excision and lymphadenectomy, immune therapy with 6.0 microg pegylated interferon alpha(2b)/kg body weight, s.c., was started. Cutaneous ulcerations at the injection sites developed 9 months after treatment initiation. The patient also developed blurred vision and presented with binasal scotomas and pathological visually evoked potentials and electroretinogram. The cutaneous ulcerations slowly healed under local therapy and reduction of the concentration of the PEG-modified interferon from 0.86 to 0.43 mg/ml. The dosage was maintained. Two months later, the therapy was stopped due to disease progression. Vision subsequently recovered. Cutaneous reactions evolved at the sites of subcutaneous injections of PEG-modified interferon alpha(2b). Changes in vision can probably be attributed to immunotherapy.

[Critical (foveal) flicker fusion frequency (CFF) is helpful in differential diagnosis of organic lesions from orthoptic amblyopias]. / Die Untersuchung der kritischen (fovealen) Flickerfusions-Frequenz (CFF) hilft bei der diagnostischen Trennung organischer Läsionen von orthoptisch bedingten Amblyopien.

PURPOSE: To measure critical (foveal) flicker fusion frequencies (CFF) in normal eyes, unilateral maculopathies and neuropathies and in orthoptic amblyopias. METHODS: A newly developed apparatus (4F) with LED's measured subjective foveal CFF by ascending and descending mode in a group of normals and patients. RESULTS: The apparatus (4F) measures temporal resolution. Foveal CFF ist more reduced in neuropathies than in maculopathies. In contrast, CFF in amblyopic eyes is hardly reduced, in most cases equal or better than in the dominant fellow eye. This is independent from the visual acuity of the amblyopic eye. CONCLUSION: CFF testing is useful in the evaluation of unexplained (unilateral) reduction of visual acuity. A dissociation between visual acuity and CFF (within normal range) is present in cases of amblyopia.

Reproducibility of the data determined by scanning laser polarimetry.

BACKGROUND: Scanning laser polarimetry is a tool for measuring the retinal nerve fiber layer: both its cross-sectional surface (polarimetric data analysis) and its thickness (mean sector values). METHODS: Two observers examined 56 normal volunteers twice by means of scanning laser polarimetry (Nerve Fiber Analyzer type 1, software version 1.6). Measurements of the retinal nerve fiber layer were carried out in four equal sectors of a circle around the optic nerve head. The measured values of the sectors and the calculated ratios among them were used for statistical analysis. Interobserver and intraobserver reproducibility were analyzed following a balanced random three-way cross classification with interactions. Interobserver reproducibility was defined as the part of variance not influenced by the observers. Intraobserver reproducibility was defined as the part of variance not influenced by the time. RESULTS: For repeated measurements of the retinal nerve fiber layer, better intraobserver than interobserver reproducibility was found (0.57-0.79 vs 0.11-0.44). The interobserver reproducibility was improved (0.24-0.65) in comparison to the intraobserver reproducibility (0.32-0.68) by calculating the ratios of the measured values. CONCLUSION: The instrument is clinically useful only if used by the same observer. If measurements are performed by different observers the ratios of the measurements must be used. Further development in the apparatus is needed to improve interobserver reproducibility.

Pattern electroretinogram, visual evoked potential and psychophysical functions in maculopathy.

To compare pattern electroretinograms and visual evoked potentials with psychophysical examinations, such as visual acuity, static (automated) perimetry and color vision in unilateral maculopathies of various origins, 20 patients with unilateral retinal diseases within the macula and the posterior pole were tested. Pattern electroretinography, visual evoked potential testing and static perimetry (Octopus program M1) were performed with three different test field sizes (20 degrees x 20 degrees, 10 degrees x 10 degrees and 6 degrees x 6 degrees). The best correlation in all three test field sizes was found between visual acuity, static perimetry and visual evoked potential. This result is surprising, since central area defined functions (visual evoked potentials, visual acuity) correlated well with a total area integrating function (mean defect in static perimetry. The pattern electroretinogram, which seems to reflect an area-related function as well, showed a correlation to static perimetry only in the smaller 10 degrees x 10 degrees and 6 degrees x 6 degrees fields and not a significant correlation in the 20 degrees x 20 degrees field. Smaller stimulation fields may therefore produce sharper results in pattern electroretinographic testing. There was no correlation between pattern electroretinograms and visual evoked potentials or visual acuity. The pattern electroretinogram was recorded under monocular and binocular viewing conditions. In 60% of the patients, the amplitude of the affected eye was more reduced in the monocular than the binocular viewing condition; the healthy fellow eye controlled stable fixation of the affected eye more readily during binocular pattern electroretinogram registration. The degree of the color vision disturbance (C-index, desaturated panel D-15 test) did not correlate to any of the other examinations.

Pattern electroretinogram and visual evoked potential amplitudes are influenced by different stimulus field sizes and scotomata.

The pattern electroretinogram and the visual evoked potential were recorded simultaneously with various stimulus fields and artificial scotomata of increasing sizes. In contrast to an earlier study, a smaller check size (20') and two stimulus field sizes (20 degrees x 20 degrees and 10 degrees x 10 degrees) for the scotomata were used. With a concentric decreasing stimulus field, a reduction of both the pattern electroretinogram and visual evoked potential was found. Both showed a simultaneous reduction of amplitudes, but, compared with the amplitude in the full field, the reduction was more extensive for the pattern electroretinogram at each test field size. This implies a greater contribution to the pattern electroretinogram from more eccentric retinal parts. An artificial central scotoma of increasing size in the 20 degrees x 20 degrees field had less influence on the pattern electroretinogram than on the visual evoked potential. The percentage amplitude loss of the visual evoked potential was more pronounced. The visual evoked potential was eventually abolished by a scotoma size from 10 degrees x 10 degrees upward, while the pattern electroretinogram was still registrable. When scotomata of similar size were introduced in a smaller (10 degrees x 10 degrees) field, percentage pattern electroretinogram and visual evoked potential amplitude losses were less separated than in a larger (20 degrees x 20 degrees) test field.

[Discrete media clouding and its effect of contrast transfer coefficients, the pattern ERG and contrast sensitivity]. / Die diskrete Medientrübung und ihr Einfluss auf den Kontrastübertragungs-Koeffizienten, das Pattern-ERG sowie die Kontrastempfindlichkeit.

As a model for our study we selected 11 pseudophacic patients with secondary cataracts who experienced good postoperative visual acuity after extracapsular cataract extraction. Besides best visual acuity and contrast sensitivity Pattern-ERG (PERG) and Contrast-Transfer-Ratio (CTR) were measured before and after YAG-Kapsulotomy was performed. Visual acuity and contrast sensitivity increased in all patients after treatment, whereas CTR increased in eight patients. PERG was measured in five patients, in two cases its amplitudes were higher, the other measurements revealed unchanged or lower amplitudes. Our model shows that in addition to the usual psychophysic tests, with CTR and PERG there are objective methods available to measure discrete opacities of the visual system.

The influence of pattern size on amplitude, latency and wave form of retinal and cortical potentials elicited by checkerboard pattern reversal and stimulus onset-offset.

Transient pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) were recorded with checkerboard pattern reversal and equiluminance stimulus onset-offset, elicited by a high quality moving mirror stimulator. Different sized checkerboard patterns (0.35-4.2 c/deg) were used as stimulus patterns. The wave forms of the equiluminance stimulus onset responses were similar to ERGs evoked with luminance decrease and the stimulus offset PERGs were like ERGs elicited by luminance increase. The PERG c wave and the VEP showed spatial frequency tuning with pattern reversal and stimulus offset. Spatial frequency tuning was not detectable with PERG a and b waves. Pattern reversal and stimulus onset evoked PERGs had no major spectral components above 40 Hz; stimulus offset evoked PERGs contained components up to 55.3 Hz. Retino-cortical time--measured as a latency difference of the PERG b wave to VEP P100--was identical with pattern reversal and stimulus onset and about 12 msec longer with stimulus offset. Our results suggest that the 3 stimulation modes, reversal, onset and offset induce different types of processing at the retinal and cortical levels. PERG a and b waves to our high luminance/contrast stimuli contain no pattern specific information and the c waves are the sum of luminance and pattern specific responses.

A comparative study of visual evoked potentials and of retinal nerve fiber layer photography in neuropathies of the optic nerve.

The degree of retinal nerve fiber loss within the papillomacular bundle in optic neuropathies was evaluated from red-free fundus photographs. Visual evoked potentials were obtained from pattern reversal with variable check sizes. A semiquantitative scale was used for the estimation of nerve fiber loss and amplitude reduction of the visual evoked potentials. A significant correlation was found between both. However, a few patients showed rather well-preserved visual evoked potentials with an atrophic nerve fiber layer. Possibly a small number of invisible remaining fibers are able to sustain nearly normal visual evoked potentials. On the other hand, some patients had abnormal visual evoked potentials in the presence of a normal nerve fiber layer. We conclude that evaluation of the nerve fiber layer of the papillomacular bundle without functional testing of the optic nerve is not sufficient to predict degree of foveal integrity.

[How good are the correlations between contrast sensitivity and differential light sensitivity in the visual field center in optic neuropathies?]. / Wie gut sind subjektive Kontrastwahrnehmung und Lichtunterschiedsempfindlichkeit im Gesichtsfeldzentrum von Opticusneuropathien miteinander korreliert?

Contrast sensitivity (CS) and differential light sensitivity (LUE) tend to deteriorate with increasing severity of the neuropathy. However, the correlation between the two psychophysical functions is low for the total number of optic neuropathies as well as for groups with different visual acuities. This fact is mainly explained by the range of scatter in LUE values. Moreover, visual acuity is much better correlated with CS than with LUE. CS and LUE represent different visual functions that may be processed by separate neural structures.

Fluctuations of visual evoked potential amplitudes and of contrast sensitivity in Uhthoff's symptom.

Visual evoked potentials (VEPs) to pattern reversal and psychophysical contrast sensitivity (CS) were tested in five patients with Uhthoff's symptom before and after exercise. Four of the cases were related to a demyelinating disease and one patient had a severe brain injury. Uhthoff's symptom occurred also in neuropathies without previous clinical neuritis and in eyes with normal latency time of the VEPs. A depression of CS was observed by all five patients after exercise; a transient "overshoot" of CS following the depression was present in three of the patients. VEP amplitudes were reduced by exercise in three cases. Responses by stimulation with small checks were more affected. Paradoxical increased VEP amplitudes after exercise in the presence of a loss of psychophysical CS were found in one case.

[Acquired disorders of contrast sensitivity and color vision in mild optic neuropathies]. / Zur Untersuchung erworbener Störungen des Kontrastsehens und der Farbwahrnehmung bei milden Optikusneuropathien.

In mild optic neuropathies (with full Snellen visual acuity), contrast sensitivity to low spatial frequencies is reduced and the scatter of the threshold determination is increased. Perception of desaturated colors is also reduced. Pattern visual evoked potentials to small checks only reveal a loss of foveal neural channels.

Neuropathies of the optic nerve and visual evoked potentials with special reference to color vision and differential light threshold measured with the computer perimeter OCTOPUS.

The contrast evoked potentials (VEPs) to different check sizes were recorded in about 200 cases of discrete optic neuropathies (ON) of different origin. Differential light threshold (DLT) was tested with the computer perimeter OCTOPUS. Saturated and desaturated tests were applied to evaluate the degree of acquired color vision deficiency. Delayed VEP responses are not confined to optic neuritis (RBN) alone and the different latency times obtained from other ON are confluent. The delay may be due to demyelination, to an increasing dominance of paramacular VEP subcomponents or to an increasing dominance of the upper half-field responses. Recording with smaller check sizes has the advantage that discrete dysfunctions in the visual field (VF) center are more easily detected: a correlation between amplitudes and visual acuity is best in strabismic amblyopias, is less expressed in maculopathies of the retina and weak in ON. The absence or reduction of amplitudes to smaller check sizes, however, is an important indication of a disorder in the VF center of ON in an early or recovered stage. Acquired color vision defects of the tritan-like type are more confined to discrete ON, whereas the red/green type is reserved to more severe ON. The DLT of the VF center is reduced in a different, significant and non significant extent in discrete optic neuropathies and the correlation between DLT and visual acuity is weak. A careful numerical analysis is needed in types of discrete ON where the central DLT lies within normal statistical limits: a side difference of the DLT between the affected and the normal fellow eye is always present. Evaluation of visual fatigue effects and of the relative sensitivity loss of VF center and VF periphery may provide further diagnostic information.

[Detection of central perceptual decrement in optic neuropathies with computer perimetry (Octopus) and visual evoked potentials]. / Zum Nachweis der zentralen Empfindlichkeitsverminderung bei Optikus-Neuropathien mit der Computerperimetrie (Octopus) und mit den visuell evozierten Potentialen (VEP).

Contrast sensitivity, as far as tested with pattern-VEPs, and light-difference sensitivity, psychophysically tested with the Octopus in the visual field center, seem to reflect different visual functions, because they are disturbed to a different degree in discrete neuropathies: light-difference sensitivity may be within normal range and a careful numerical analysis is needed in order to find pathologic differences. With VEPs, on the other hand, it is easier to detect a loss of normal neural conduction.

[Visual evoked potentials in the evaluation of suspected simulation and aggravation]. / Die visuell evozierten Potentiale (V.E.P.) bei der Abklärung von Simulations- und Agrravationsverdacht.

Visual evoked potentials (VEP) with checkerboard stimulation are good reference for the function of the visual pathways. Normal VEP are registered from simulants and better than expected VEP are noted from aggravants. However an exact objective determination of the visual acuity is limited, due to the low correlation between retinal resolution and stimulus parameters.

Idiopathic hypercalciuria with bilateral macular colobomata: a new variant of oculo-renal syndrome.

Two siblings from a consanguineous family, suffering from nephrocalcinosis and nephrolithiasis caused by idiopathic hypercalciuria are described. The condition is associated with bilateral macular colobomata and tapeto-retinal degeneration. It is known that the latter can occur together with different nephropathies; however, until now it has never been described in combination with idiopathic hypercalciuria. Blood calcium levels were found to be normal, calcium excretion rates were, with one exception, more than 6 mg/kg/24 h corrected for 100 ml GFR. Hypomagnesemia of 1.5 and 1.2 mg/dl and hyermagnesuria of 1.9 and 2.5 mg/kg/24 h corrected for 100 ml GFR were found in both patients. Tubular phosphate reabsorption reached 87% and 84% at serum parathormone levels of 0.34 microgram/l and 0.31 microgram/l in the two patients, respectively. Under calcium and magnesium loading the clearance rates of calcium and magnesium were raised whilst there was only a small insignificant increase in the blood levels of these cations. Acid-base titrations showed normal excretion rates of acid and base in one patient and a mild proximal tubular acidosis in the other. Quantitative investigation of the renal concentrating and diluting capacity established a decrease in the formation of the medullary concentrating gradient in both patients.

[Eye movement disorder in albinos (author's transl)]. / Zur augenmotorischen Störung des Albino.

Recent studies have shown misdirected optic fibres in albinotic animals to the lateral geniculate body, to the visual cortex and to the superior colliculi. Since a similar anomaly was found anatomiclly and neurophysiologically in human albinos, an oculography was performed in 10 albinos. The results were identical to those found in the so called congenital nystagmus. It remains doubtful that the misdirection is an explanation for the nystagmus in albinotic humans.

Differential diagnostic aspects between optic neurititis and chiasm tumors.

Two patients with a pituitary tumor were first considered to have an optic neuritis from the clinical picture. The electrophysiological examination with VECPs gave results which did not offer a definite differentiation between both diseases, whereas perimetry and X-ray examination were decisive.