Genotype-phenotype correlation and longitudinal course in ten families with Best vitelliform macular dystrophy.

AIM: Longitudinal course and genotype-phenotype correlation in patients and carriers with heterozygous mutations in hBEST1 (bestrophin). METHODS: Thirteen patients and seven possible carriers were characterised by mutation analysis with SSCPA and direct sequencing, clinical examination and fundus autofluorescence (AF). Electrophysiology (EOG and mfERG) and optical coherence tomography (OCT) were additionally performed whenever possible. RESULTS: We identified seven different heterozygous mutations in ten unrelated families with Best disease. I296del was the most frequent mutation. Five of nine individuals with I295del and two of three with N99K were asymptomatic carriers. One patient with I295del mutation had funduscopically unilateral Best disease. In three children (all with I295del), EOG initially showed a clearly present light peak that deteriorated during 5 years of follow-up in two of them. Increased AF corresponded well to funduscopically visible lesions. During 3-6 years of follow-up, the lesion area did not change significantly, but there were obvious changes in the inner structure of the lesion. CONCLUSION: In the present series I295del, the most frequent mutation in our study, and N99K showed reduced penetrance. EOG was normal in young patients even if prime signs were visible. The lesion area did not depend on the mutation and did not correlate with VA. Lower VA was associated with a more irregular AF pattern due to scarring or haemorrhage. Our results indicate a disease causing effect that is cumulative over time.

Clinical applications of multifocal electroretinography.

The multifocal ERG using the m-sequence stimulation technique allows the derivation of 61 - 241 local ERG signals in a central visual field of about 60 degree diameter in a short time between 4 and 16 min. A recording in a light adapted state offers local information comparable to cone responses in the full-field ERG. Retinal functional losses due to regional disorders in outer retinal layers can be described in detail with this technique. In maculopathies decreased or absent central ERGs are found surrounded by normal ERG. The extent of the central lesion can be estimated. In diseases of the outer retina the pattern of distribution of multifocal ERG activity is similar to the the pattern of the visual field defect. In addition to decreased ERG amplitudes a delay of implicit time may be an important sign of pathology, i.e. the pronounced delay of implicit times in the periphery in retinitis pigmentosa and the implicit time delays in regions associated with retinal edema like CRVO and cystoid macula edema in intermediate uveitis. No simple correlation of the first order kernel multifocal ERG and field defects could be found in disorders of the ganglion cell layer. The multifocal ERG is therefore useful in the differential diagnosis of retinal and optic nerve diseases.

Minimal invasive decompression of the orbit in Graves' orbitopathy.

BACKGROUND: Surgical decompresssion of the orbit may be considered as a suitable form of therapy if, as a result of the increased volume inside the orbit, there are motility disorders such as diplopia or a progressive decrease in visual acuity. In view of the fact that this operation will not cure the underlying disease, the treatment should be as mild as possible. METHODS: In five subjects with Graves' orbitopathy we managed to extend the volume of the intraconal orbit by microsurgical liposuction. We carried out a lateral canthotomy to approach the orbit behind the globe. After decompression of the soft tissue, the lateral palpebral ligaments were refixed. To assess the scale of the functional rehabilitation we compared preoperative parameters (visual acuity, Hertel's index, visual field, motility) with the postoperative results. RESULTS: In all cases we found a significant improvement of position and motility without signs of diplopia. There was a postoperative increase in the visual field and visual acuity was 0.4 and the protusion of the globe could be decreased by 3-6 mm (Hertel's index). Furthermore, the ocular hypertension we found preoperatively could no longer be detected after the operation. CONCLUSIONS: Microsurgical decompression of the soft tissue via an approach from behind the globe proved to be a very gentle alternative to conventional methods of orbital decompression because of the satisfying functional and esthetic rehabilitation in selected cases.

Pupil perimetry using M-sequence stimulation technique.

PURPOSE: M-sequence stimulation technique allows mapping of the retinal function by multifocal electroretinographic (ERG) recordings. However, the information provided about visual field is limited to retinal function. Optic nerve diseases and diseases of the higher visual pathways usually show normal multifocal ERGs. Using pupillary responses instead of the electrical retinal responses might enhance the diagnostic possibilities of this system. The problems of local ERG recordings are very similar to those encountered in pupil perimetry: Local stimuli have to be dim to avoid or at least reduce stray-light responses. Dim stimuli, close to the absolute threshold, elicit only subtle pupillomotor responses. Therefore, techniques that are able to detect small focal responses are promising. METHODS: Pupillography was done by means of an infrared video camera and real time image processing (50 Hz) using a custom-designed videoboard in a personal computer (486). Recording conditions: The stimulus was presented on a monitor (75 Hz) in 26 cm distance from the patient's eyes. It contained 37 hexagons in a 25 degrees visual field. Each element changed between black (1.6 cd/m2) and white (160 cd/m2) after a binary M-sequence independently from other elements. Four thousand ninety six different stimulus pictures of 120-msec duration were shown during a single pupillogram recording. Thirty-seven local pupillograms were calculated in a cross-correlation of stimulus sequence and the pupil diameter. RESULTS: The pupillomotor fields in normals showed a shape and sensitivity distribution as known from conventional pupil perimetry techniques. Artificial paracentral scotomas (5 degrees) created by masking different locations could be demonstrated convincingly. Even in patients with optic nerve lesions it was possible to demonstrate visual field defects. CONCLUSIONS: Pupil perimetry using the M-sequence technique is a promising method of objective perimetry that may find its entrance into clinical application.

Familial macular cone dystrophy: diagnostic value of multifocal ERG and two-color threshold perimetry.

BACKGROUND: It is difficult to detect receptor dysfunction in patients with marked bilateral visual loss but only mild morphological alterations of the fundus. METHODS: Two patients, father and son, with visual acuity loss to 20/100 were examined. Using the multifocal ERG, 61 local cone ERGs from each eye were derived from the central visual field. The dark-adapted two-color threshold perimetry using stimuli of 500 nm and 656 nm for rod and cone function was investigated along the horizontal meridian of the visual field. RESULTS: In the multifocal ERG of both patients a macular response was absent. From eccentricity at and anterior to 5 degrees, good multifocal cone activity was recorded. Cone thresholds were markedly diminished in the macula. The rod thresholds were borderline in the father and normal in the son. CONCLUSIONS: Multifocal ERG is a novel technique, very well suited to reveal the topography of cone function. Using two-color threshold perimetry affords an opportunity to differentiate between rod and cone functional defects. Both together helped to establish the diagnosis of macular cone dystrophy in the present family.

Multifocal ERG reveals long distance effects of a local bleach in the retina.

To examine the distribution of ERG-activity in the central visual field after local bleaching of the fovea, multifocal electroretinograms were recorded in eight normal volunteers before, during and after recurrent light exposure. During bleaching (90% bleached pigment), the response density (scalar product) of the foveal area (0-2 degrees eccentricity) decreased from 10.7 +/- 3.5 to 4.1 +/- 1.9 nV/degree2 (P < 0.001). The average activity in the extrafoveal macular area was unchanged, while the amplitudes were frequently (in 53 of 54 areas) enhanced at 5-30.5 degrees eccentricity. Here the average response density changed from 3.1 +/- 0.9 to 3.5 +/- 1.0 nV/degree2 (P < 0.001). A fast recovery of foveal responses after cessation of bleaching occurred. Besides a strong decrease of response in the directly bleached area, local bleaching led to enhanced activity mainly 3-27 degrees distant from the bleached area.

[Objective assessment of visual field defects using multifocal electroretinography]. / Objektivierung von Gesichtsfelddefekten mit Hilfe der multifokalen Elektroretinographie.

BACKGROUND: Multifocal electroretinography allows simultaneous recording of 61 focal electroretinographic signals from the retina of the posterior pole. The function of the outer retinal layers can be mapped for a visual field of 30.5 degrees radius. We herein describe the topography of such potentials in patients with hemianopic and concentric visual field defects. SUBJECTS AND METHODS: Six patients with visual field defects caused by chorioretinal and central visual pathways diseases were examined using multifocal ERG. RESULTS: In 30 normal volunteers in the entire 30 degrees visual field clear signals were obtained. In the patients with visual field defects caused by retinal diseases in areas with reduced light sensitivity diminished electroretinographical activity was found. In contrast, in patients with bitemporal hemianopsia due to a chiasmal lesion no correlation between visual field and magnitude of focal ERGs was seen. CONCLUSIONS: In retinal disorders defects in multifocal ERG presented the similar pattern as scotomata in perimetry. The patient with visual field defects due to disturbances in the chiasma exhibited a normal ERG-topography. In patients with visual field defects multifocal ERG supported differentiation of the location of the lesion.

Multifocal electroretinography in patients with Stargardt's macular dystrophy.

AIMS: To describe the topography of multifocal electroretinograms (ERGs) and to explore its diagnostic value in patients with Stargardt's macular dystrophy (SMD). METHODS: 51 patients with SMD were examined by means of the m-sequence technique to characterise the topography of electroretinographic responses in the central visual field. The results were compared with data from 30 normal volunteers. RESULTS: In 49 of 51 patients with SMD, macular electroretinographic activity was markedly diminished or non-detectable. Towards more peripheral areas, ERG responses of the SMD patients approached those of normals. Implicit times were not markedly delayed at any eccentricity. CONCLUSION: In contrast with Ganzfeld electroretinography, multifocal electroretinography is useful to detect foveal dysfunction in SMD. Areas of dysfunction were found to be usually larger than expected from psychophysical measurements and morphological alteration. In early stages of the disease it was possible to detect foveal dysfunction, even in patients lacking morphological fundus changes and with good visual acuity.

[Multifocal electroretinography in acquired macular dysfunction]. / Multifokale Elektroretinographie bei erworbenen Makulafunktionsstörungen.

BACKGROUND: Multifocal electroretinography allows physiological mapping of the central retina. The purpose of this study was to describe the spatial distribution of ERG-activity in patients with impairment of macular function which usually do not exhibit a pathologic Ganzfeld-ERG. SUBJECTS AND METHODS: 6 patients with macular lesions due to uveitis (4), retinitis centralis serosa (1), and contusio bulbi (1) were examined using the multifocal ERG technique. RESULTS: In normal volunteers the response density of the multifocal ERG decreased with eccentricity according to cone density distribution. In eyes with impaired central vision the foveal and macular responses were markedly diminished while surrounding signals were of normal or moderately decreased amplitudes. CONCLUSIONS: With the multifocal ERG disturbances of macular function due to oedema and secondary structural changes were detected in the presented cases and the extension of the central lesions was estimated.

Implicit time topography of multifocal electroretinograms.

PURPOSE: To describe the implicit time topography of multifocal electroretinograms in normal subjects and to examine the change in this topography in patients affected by retinitis pigmentosa. METHODS: Thirty normal subjects and 38 patients with retinitis pigmentosa were examined with the Visual Evoked Response Imaging System using 61 hexagonal elements within a visual field of 30 degrees radius. The peak implicit times of the 61 first-order kernels (which are analogues of the photopic electroretinogram [ERG]) were measured to determine their distribution across the retina. RESULTS: Implicit times had a low interindividual variability in the normal group. High implicit times were found at the blind spot, the upper and lower borders of the stimulated field, and the macula. Low values were present in the area encircling the macula and were most prominent in the temporal retina. In the group with retinitis pigmentosa, implicit times were unchanged in the central region but were prolonged in the peripheral regions. CONCLUSIONS: The spatial distribution of multifocal ERG implicit times in a normal population follows a specific topographical pattern across the retina. This pattern has to be taken into account when interpreting results in patients. Deviations in retinitis pigmentosa were found, and they show the potential for diagnostic use.

Multifocal electroretinography in retinitis pigmentosa.

PURPOSE: To investigate the diagnostic potential of multifocal electroretinography for the evaluation of retinal affection by retinitis pigmentosa in a clinical setting. METHODS: For this prospective study, multifocal electroretinograms were obtained from 38 patients who matched the inclusion criteria of either a detectable photopic Ganzfeld response or visual fields of 10 degrees or more, and from 30 normal volunteers. Recordings were performed with the visual evoked response imaging system, using a resolution of 61 hexagonal elements within a 30-degree visual field. The results of the left eye of each patient and control subject were used for statistical evaluation by the Mann-Whitney U test. RESULTS: The 38 eligible patients included those with Usher syndrome types I and II (one patient and six patients, respectively) and those with autosomal-recessive (18), X-recessive (two), and autosomal-dominant (11) forms of retinitis pigmentosa. In 27 (71%) of these 38 patients, at least a central response of the multifocal electroretinogram was detectable. Loss of multifocal electroretinogram response density in patients with retinitis pigmentosa was significant (P < .00001) in all five eccentricity groups (concentric rings), with a progression from center to periphery. Implicit time was significantly elevated in the third eccentricity group (P < .0038) and increased further toward the periphery (P < .00001). The results did not differ notably between retinitis pigmentosa subgroups. CONCLUSIONS: Because the multifocal electroretinogram differentiates between affected and nonaffected retinal areas, eccentricity-dependent changes in both amplitude and implicit time were found. It can therefore add to the diagnostic information of many patients with retinitis pigmentosa.

Spatial cone activity distribution in diseases of the posterior pole determined by multifocal electroretinography.

Thirty patients with a reduced central vision due to diseases of the posterior pole were examined with the VERIS system developed by Sutter and Tran (Vis Res 1992;32:433-446) to characterize the topography of electroretinographic (ERG) changes in comparison to the results in 30 normal volunteers. Diagnoses included Stargardt's macular dystrophy (SMD, n = 10), age-related macular degeneration (AMD, n = 5), cone dystrophy (CD, n = 5), central retinal vein occlusion (CRVO, n = 5), and autosomal dominant optic atrophy (ADOA, n = 5). The 61 local responses obtained from each subjects were grouped by eccentricity to form five concentric rings. The foveal ERG, originating from a central area of 2 degrees radius, was non-recordable or markedly diminished in all patients except those with optic atrophy, where amplitudes were found to be in the normal range. In patients with advanced stages of SMD, functional defects were larger and involved more peripheral areas than in patients with early stages of SMD or with AMD. A reduction of response amplitude even in the most peripheral ring (17-30.5 degrees eccentricity) was found in cone dystrophies and--moderately--in patients with advanced SMD and central retinal vein occlusion only. Prolonged implicit times were found in all but the patients in early stages of SMD and they were maximal in patients with CRVO. This study shows that the multifocal ERG (MFERG) can contribute to differential diagnosis of retinal diseases of the posterior pole especially in cases with a normal photopic Ganzfeld ERG.

[Phototoxic maculopathy after arc welding: value of multifocal ERG]. / Phototoxische Makulopathie nach Lichtbogenschweissen: Stellenwert des multifokalen ERG.

BACKGROUND: Phototoxic maculopathy most likely results from longer exposure to light from sources such as the sun, welding arcs, tungsten halogen lamp filaments or operation microscopes. The value of the multifocal ERG for the evaluation of functional defects in this rare entity has not been described to date. CASES: We describe the case of a 38-year-old male patient who presented to his local ophthalmologist with bilateral loss of vision and acute ocular pain after having worked for two hours at an electric welding arc. A foveal lesion was found in both eyes, resulting in a bilateral reduction of visual acuity. Nine months later, the patient underwent examination and further investigations at the university eye clinic in Tübingen. Visual field defects on both sides could be detected with automatic threshold perimetry. Using the multifocal ERG with a central element of 2 degrees diameter, a central defect was detected only for the right eye. CONCLUSIONS: In rare cases, a photic maculopathy can result from exposure to light during arc welding. It can be masked in the first days by a phototoxic keratitis. Multifocal ERG and automatic perimetry are useful tools for the detection and quantification of the functional defects.

Electroretinographic campimetry in a patient with crystalline retinopathy.

We report the findings we obtained by multifocal electroretinography (ERG) in a patient with crystalline retinopathy. Although the conventional Ganzfeld (full-field) ERG was within the normal range, the amplitudes were reduced and implicit times were delayed in the parafoveolar region in the multifocal ERG. To our knowledge, this is the first report on crystalline retinopathy investigated with this spatially differentiating electrophysiologic method, which is useful for the detection of early change in this disease.

ERG campimetry using a multi-input stimulation technique for mapping of retinal function in the central visual field.

The m-sequence stimulation technique that has previously been described allows simultaneous recording of many local electroretinograms (ERGs). For topographical mapping of cone function in the central retina ERG traces from 61 retinal areas were recorded during a 4-min period in 20 normal volunteers and 4 patients with age-related macular degeneration, Stargardt's disease, choroidal atrophy, and polymyalgia associated with visual field loss. The local photopic luminance response was analyzed in each of the 61 areas. In the 2 patients with macular disease central defects were detected, in the remaining patients local defects were found outside the macular region. The method of multifocal ERG recordings provides the possibility of objective testing of visual fields when the outer retinal layers are affected.

[Increased spontaneous and evoked response in the area of model infarcts of the visual cortex of cats]. / Erhöhte Spontan- und Reizantwortakivität in der Umgebung von Modellinfarkten im visuellen Kortex von Katzen.

Ischemic lesions were produced in the cat visual cortex and changes of responses to visual stimuli were studied in single cells with extracellular recordings. The spontaneous and the visually driven activity were quantitatively analyzed and compared with those in normal controls. While the normal control cells showed a mean response strength of 52.7 impulses/s, this value was increased to 69.3 impulses/s in the vicinity of ischemic lesions. The spontaneous activity was also increased. Epileptiform burst activity with frequencies above 500 I/s was observed in 37.7% of the cells. Directional and orientational specificity was significantly reduced in these regions because of an increase in responses to stimuli in non-preferred directions and with non-preferred orientations. Thus, an increase in activity-dependent energy consumption occurs in the vicinity of lesions in the ischemically severed cortex.