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Biomedical subjects

F W Fitzke

Publications and source records attributed to F W Fitzke.

At least 91 records · Page 5Linked to original sources

Modelling series of visual fields to detect progression in normal-tension glaucoma.

BACKGROUND: Use of statistical modelling techniques to identify models that both describe glaucomatous sensitivity decay and allow predictions of future field status. METHOD: Twelve initially normal fellow eyes of untreated patients with confirmed normal tension glaucoma were studied. All had in excess of 15 Humphrey fields (mean follow-up 5.7 years). From this cohort individual field locations were selected for analysis if they demonstrated unequivocal deterioration at the final two fields. Forty-seven locations from five eyes satisfied this criterion and were analysed using curve-fitting software which automatically applies 221 different models to sensitivity (y) against time of follow up (x). Curve-fitting was then repeated on the first five fields, followed by projection to the date of the final field to generate a predicted threshold which was compared to the actual threshold. Competing models were therefore assessed on their performance at adequately fitting the data (R2) and their potential to predict future field status. RESULTS: Models that provide the best fit to the data were all complex polynomial expressions (median R2 0.93). Other simple expressions fitted fewer locations and exhibited lower R2 values. However, accuracy in predicting future deterioration was superior with these less complex models. In this group a linear expression demonstrated an adequate fit to the majority of the data and generated the most accurate predictions of future field status. CONCLUSIONS: A linear model of the pointwise sensitivity values against time of follow-up can provide a framework for detecting and forecasting glaucomatous field progression. Linear modelling allows the clinically important rate of sensitivity loss to be estimated.

Cohort Studies↗

Autosomal dominant retinitis pigmentosa mapping to chromosome 7p exhibits variable expression.

The genetic locus causing autosomal dominant retinitis pigmentosa (adRP) has recently been mapped in a large English family to chromosome 7p. Eight affected members of this family were studied electrophysiologically and psychophysically with dark adapted static threshold perimetry and dark adaptometry. The phenotypes observed fell into three categories: minimally affected with no symptoms, and normal (or near normal) electrophysiology and psychophysics; moderately affected with mild symptoms, abnormal electroretinograms, and equal loss of rod and cone function in affected areas of the retina; and severely affected with extinguished electroretinograms and barely detectable dark adapted static threshold sensitivities. The mutation in the gene on 7p causing adRP in this family causes regional retinal dysfunction with greatly variable expressivity ranging from normal to profoundly abnormal in a manner not explained by age.

Adult↗

Motion detection threshold and field progression in normal tension glaucoma.

Psychophysical tests may demonstrate abnormalities of visual function before the appearance of conventional visual field loss in glaucoma. Motion detection thresholds (MDT) were measured in the normal fellow eye of 51 patients with confirmed normal tension glaucoma and initially unilateral field loss. Humphrey visual fields from the initially normal eye covering a mean follow up of 3.4 years were assessed using pointwise linear regression analysis. In 22 of the 51 eyes with normal visual fields at presentation, field deterioration occurred at one or more Humphrey locations within a mean of 1.7 (SD 1.6) years. An initially abnormal MDT test showed a sensitivity of 73% and a specificity of 90% in predicting field deterioration within the cluster of four Humphrey locations closest to the original MDT test site. Sensitivity was lower (40%) in predicting progression at retinal locations distant from the MDT test site, though specificity remained high (90%).

Aged↗

Image processing of computerised visual field data.

BACKGROUND: Computerised perimetry is of fundamental importance in assessing visual function. However, visual fields are subject to patient response variability which limits the detection of true visual loss. METHODS: A method of improving the repeatability of visual field data was demonstrated by applying techniques used in image processing. An illustrative sample of nine normals and nine patients with field loss was used. Two successive Humphrey fields were selected for each subject. Repeatability was defined as the standard deviation of the pointwise differences between sensitivity values of the reference field and repeat field. The field data were then separately subjected to Gaussian and median image processing filters and the repeatability was compared with the unprocessed field results. RESULTS: Improvement in repeatability, by a factor of approximately 2, was demonstrated by both processes. CONCLUSION: These techniques may improve the reliable detection of loss of visual function using computerised perimetry.

Adult↗

New approach to estimating variability in visual field data using an image processing technique.

AIMS: A new framework for evaluating pointwise sensitivity variation in computerised visual field data is demonstrated. METHODS: A measure of local spatial variability (LSV) is generated using an image processing technique. Fifty five eyes from a sample of normal and glaucomatous subjects, examined on the Humphrey field analyser (HFA), were used to illustrate the method. RESULTS: Significant correlation between LSV and conventional estimates--namely, HFA pattern standard deviation and short term fluctuation, were found. CONCLUSION: LSV is not dependent on normals' reference data or repeated threshold determinations, thus potentially reducing test time. Also, the illustrated pointwise maps of LSV could provide a method for identifying areas of fluctuation commonly found in early glaucomatous field loss.

Adult↗

Distribution of fundus autofluorescence with a scanning laser ophthalmoscope.

BACKGROUND: Variation of fluorescence derived from lipofuscin in the retinal pigment epithelium has been recorded with age and in retinal diseases. Studies have been based largely on in vitro observations on eye bank eyes which has placed severe limitations on the data available. METHODS: A technique is described whereby in vivo imaging of autofluorescence of the fundus was achieved using a scanning laser ophthalmoscope. RESULTS: The optical characteristics, distribution, and variation with disease imply that the fluorescence is derived from lipofuscin in the pigment epithelium. Autofluorescence is shown to be abnormally high in certain inherited diseases, and low in the presence of retinal atrophy. CONCLUSION: This technique may be useful both in clinical practice and research. It may allow the detection of the abnormal phenotype in genetically determined disease at a time when other techniques may not. Longitudinal studies of age related macular disease would permit correlation between changes in the pigment epithelium and Bruch's membrane to be established.

Adolescent↗

Bimodal expressivity in dominant retinitis pigmentosa genetically linked to chromosome 19q.

A clinical, psychophysical, and electrophysiologic study was undertaken of two autosomal dominant retinitis pigmentosa pedigrees with a genetic mutation assigned to chromosome 19q by linkage analysis. Members with the abnormal haplotype were either symptomatic with adolescent onset nyctalopia, restricted visual fields, and non-detectable electroretinographic responses by 30 years of age, or asymptomatic with normal fundus appearance and minimal or no psychophysical or electroretinographic abnormalities. There was no correlation in the severity in parents and their offspring. Pedigree analysis suggested that although the offspring of parents with the genetic mutation were at 50% risk of having the genetic defect, the risk of being symptomatic during a working lifetime was only 31%. Such bimodal phenotypic expressivity in these particular pedigrees may be explained by a second, allelic genetic influence and may be a phenomenon unique to this genetic locus. Genetic counselling in families expressing this phenotype can only be based on haplotype analysis since clinical investigations, even in the most elderly, would not preclude the presence of the mutant gene.

Adult↗

Fine matrix mapping of the macular region in normal subjects.

Using a Humphrey field analyzer and fine matrix mapping, we measured photopic and scotopic thresholds for a blue light stimulus at 100 locations on a 9 degrees by 9 degrees matrix of 1 degree spacing centered at the fovea in 14 normal subjects. Additionally, trial lenses were used to investigate the effect of refractive error. Under photopic conditions the mean sensitivity varied by less than 1 dB over this region. Under scotopic conditions the central values were reduced in sensitivity by 15 dB compared with those at 4 degrees eccentricity. Defocus showed less than 1.2 dB loss with 1.00D of refractive error under photopic condition. The results reflect the properties of rod and cone photoreceptors and the effects of the rod mosaic near the fovea. This technique is a sensitive test of macular visual function.

Adult↗

Cutaneous melanoma-associated retinopathy.

PURPOSE: To define further the syndrome of cutaneous melanoma-associated retinopathy, of which only five affected patients have been reported previously. METHODS: Three men with melanoma-associated retinopathy were examined and studied electrophysiologically. Two were studied in detail psychophysically. RESULTS: Visual symptoms consisted of flickering black and white spots, shimmering patches of colors, and night blindness. The onset was acute and nonprogressive. Reduced amplitudes were observed in the flash electroretinographic b-wave and the pattern electroretinogram. Color vision, contrast sensitivity, and light- and dark-adapted perimetric sensitivities were abnormal. In one patient, the rate of dark adaptation was normal with elevated final cone and rod thresholds. CONCLUSIONS: Melanoma-associated retinopathy is a paraneoplastic syndrome distinct from cancer-associated retinopathy with a different visual prognosis. It may preferentially affect men.

Aged↗

Disturbances in night vision after excimer laser photorefractive keratectomy.

Eighty-four patients with up to -6.00 dioptres of myopia underwent photorefractive keratectomy (PRK), using 5.00 mm ablation zones. Three months post-operatively 38 (45%) complained of disturbances in night vision, compared with 21 (25%) pre-operatively. In the majority, these disturbances were regarded as negligible. However, 9 (11%) reported significant problems, defined as an inability to drive safely at night with the treated eye. At 12 months, 32 patients (38%) complained of impaired night vision, 4 (5%) of whom had significant problems. A series of measurements were performed to investigate the origins of these disturbances, especially in patients reporting significant problems. Visual impairment from forward scattered light was investigated using a computerised technique. Back scattered light was measured with a charge coupled device-camera system and a computer program was used to assess the degree of halation around a bright light source on a high-resolution monitor. Pupillary diameters were measured by infrared television pupillometry. At 6 months, those reporting a starburst effect around lights at night had small hyperopic shifts, minimal halos and high forward and back light scatter measurements. Patients who reported halo phenomena had large hyperopic shifts, little light scatter and large pupillary diameters. Of the 4 patients who reported significant disturbances at 12 months, all had persistent halo problems. Those with starburst effects in the early post-operative period noticed an improvement with time as their corneal haze gradually improved. Perturbations of night vision after PRK manifest as starbursts and halos around lights.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The diagnosis of visual field progression in glaucoma.

The detection of true visual field deterioration in glaucoma is of fundamental importance but is limited by inherent variability of the measurements. New techniques have been developed that use powerful statistical regression analysis methods to objectively quantify progression of visual field defects. These have been combined with new methods of graphical presentation to reveal the spatial distribution in the visual field of deterioration. New measurement techniques utilizing blue-on-yellow, flicker, and motion stimuli provide further advantages and may be combined with regression analysis to improve the early detection of real progression of visual field loss.

Glaucoma↗

The shape of the corneal apical zone after excimer photorefractive keratectomy.

Applying an experimental photo-keratoscope, which assesses the shape of cornea within the pupillary region, to a group of subjects who have undergone excimer laser photorefractive keratectomy over a central 4 mm chord diameter of the cornea, we report the shape of the typical cornea within the ablated zone conforms to a steepening ellipse (average shape factor, 1.25). A statistically significant difference in the mean shape factor (asphericity) between the photoablated and the normal cornea (average shape factor 0.89) was not confirmed. However, there is more variability in the shape factors found in the photorefractive keratectomy group compared with normals, within the same distance from the corneal apex. Using the criterion of overlap within two standard deviations, averaging the vertical horizontal meridians, 75% of photorefractive keratectomy eyes fall within the shape factor limits of the normal eye group. In all cases the post-ablated corneal surface was found to be regular in terms of surface quality alone. The excimer photorefractive keratectomy technique is therefore a clinically acceptable method of refractive surgery.

Adult↗

Ocular findings associated with a 3 base pair deletion in the peripherin-RDS gene in autosomal dominant retinitis pigmentosa.

Affected members of a family with autosomal dominant retinitis pigmentosa were found to have a 3 base pair deletion at codon 118 or 119 of the retinal degeneration slow gene. This mutation causes the loss of a highly conserved cysteine residue in the predicted third transmembrane domain of peripherin-rds, a photo-receptor specific structural glycoprotein localised to both rod and cone outer segment disc membranes. Four of these individuals underwent detailed clinical, psychophysical, and electroretinographic testing in order to characterise their photoreceptor dysfunction. Nyctalopia was reported early in the second decade by all patients. Global rod and cone dysfunction was recorded by the third decade with severe reduction of both photopic and scotopic function by age 30 years. This retinal degeneration slow gene mutation may lead to the primary loss of both rod and cone photo-receptor function.

Adult↗

Ocular manifestations in autosomal dominant retinitis pigmentosa with a Lys-296-Glu rhodopsin mutation at the retinal binding site.

A lysine to glutamic acid substitution at codon 296 in the rhodopsin gene has been reported in a family with autosomal dominant retinitis pigmentosa. This mutation is of particular functional interest as this lysine molecule is the binding site of 11-cis-retinal. The clinical features of a family with this mutation have not been reported previously. We examined 14 patients with autosomal dominant retinitis pigmentosa and a lysine-296-glutamic acid rhodopsin mutation. Four had detailed psychophysical and electrophysiological testing. Most affected subjects had severe disease with poor night vision from early life, and marked reduction of visual acuity and visual field by their early forties. Psychophysical testing showed no demonstrable rod function and severely reduced cone function in all patients tested.

Adolescent↗

Dominant retinitis pigmentosa associated with two rhodopsin gene mutations. Leu-40-Arg and an insertion disrupting the 5'-splice junction of exon 5.

OBJECTIVE: To determine the phenotypes of two families in which retinitis pigmentosa cosegregates with a rhodopsin (RHO) gene mutation: a leucine-to-arginine change at codon 40 (Leu-40-Arg) in one family, and a 150-base pair insertion that disrupts the RHO 5'-splice junction of exon 5 in another. PATIENTS: Three affected members of each family. RESULTS: The Leu-40-Arg mutation was associated with the onset of night blindness in the first decade of life. By the fourth decade, severe retinal functional loss was evident on dark-adapted static threshold perimetry, and electroretinographic responses were absent or barely detectable. In contrast, the RHO 150-base pair insertion was associated with the later onset of mild night vision difficulties; in two individuals, mild night vision difficulties were first noticed in the second decade while a third, a 25-year-old woman, was asymptomatic. Dark-adapted static threshold perimetry of this latter individual revealed a "regional" or class 2 pattern of retinal functional loss associated with equal loss of rod and cone electroretinographic responses. CONCLUSION: The RHO Leu-40-Arg mutation causes symptomatic retinal dysfunction by the end of the first decade while the insertion disrupting the 5'-splice junction of RHO exon 5 causes later onset "regional" or class 2 retinal dysfunction.

Adult↗