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Biomedical subjects

F W Fitzke

Publications and source records attributed to F W Fitzke.

At least 19 recordsLinked to original sources

Visual field progression: comparison of Humphrey Statpac2 and pointwise linear regression analysis.

BACKGROUND: Humphrey Statpac2 "glaucoma change probability analysis' is a widely available analysis technique to aid the clinician in the diagnosis of glaucomatous visual field deterioration. A comparison of this technique with the more recently described pointwise linear regression analysis (PROGRESSOR) is given. METHODS: Series of visual field data from a group of nine eyes of nine patients with normal-tension glaucoma were selected. Each series had 16 fields with mean follow-up of 5.7 years (SD 0.6 years). Statpac2 "glaucoma change probability analysis' was used to define test locations that had unequivocally deteriorated in the last three fields of each series. The accuracy of both Statpac2 and PROGRESSOR in providing early detection of these deteriorated locations was assessed. RESULTS: The sensitivity and specificity of the two techniques in predicting deteriorated locations were similar when a rate of luminance sensitivity loss of faster than 1 dB/year (2 dB/year for outer locations beyond 15 deg of eccentricity) with a slope significance of P < 0.10 was used as the regression definition of deterioration. The difficulties of comparing two techniques in the early diagnosis of field progression without a true external standard for field loss are illustrated. CONCLUSIONS: PROGRESSOR closely emulates the performance of Statpac2 in detecting sensitivity deterioration at individual test locations. This new technique, which uses all available data in a field series and gives the rate of sensitivity loss at each location, may provide a clinically useful method for detecting field progression in glaucoma.

Disease Progression

Analysis of visual field progression in glaucoma.

BACKGROUND: Despite the widespread use of computerised perimetry the diagnosis of visual field deterioration in following glaucoma patients over time remains particularly difficult. A new method of analysis using a novel graphical display of longitudinal field data is presented. METHODS: A linear regression model of the luminance sensitivity at each stimulus location against time of follow up transforms the quantitative data from a series of fields into a colour coded form which illustrates the spatial configuration of change to aid the interpretation of field loss. The method of analysis and the developed computer software (PROGRESSOR) is described. Comparison with STATPAC-2 glaucoma change probability analysis is given including levels of agreement between the techniques using series of fields of 10 eyes from patients with normal tension glaucoma. RESULTS: Examples of this new method compare well with STATPAC-2 analysis. The level of agreement between the techniques to separate progressing from stable retinal locations is good (kappa = 0.62; SE = 0.04). CONCLUSIONS: This new technique, which combines the change in perimetric sensitivity over time with colour coding of significant change into one image may provide an efficient method to detect true progression in glaucomatous field loss.

Diagnosis, Computer-Assisted

A computer model for predicting image quality after photorefractive keratectomy.

BACKGROUND: Accurately predicting visual performance remains a concern in refractive surgery. The effects of the eye's optics on retinal image quality were investigated using computer ray tracing to model the human eye after photorefractive keratectomy (PRK). METHODS: Ray-tracing analysis was used with an anatomically realistic model of the human eye including aspheric surfaces and crystalline lens gradient index distributions. The contribution of corneal curvature to refractive error was investigated using data of axial length, corneal power, anterior chamber depth, and lens power from 318 eyes from the literature. The computer interface was specifically designed for use with PRK and provides graphical plots of the remodeled eye, ray paths and retinal image formation. RESULTS: Modeling the optical contribution of corneal curvature resulted in an improvement in predicted refractive state of the eye as a function of axial length expressed as the R2 value of the regression analysis from 0.88 to 0.96. Subsequently, analyses were conducted for single and multizone treatment areas of differing diameter and with varying pupil size. Retinal image quality following PRK for the human cornea was found to be affected by not only the corneal parameters of anterior curvature and thickness, but also by axial length, pupil size, and anterior chamber depth. CONCLUSIONS: The inclusion of multiple interdependent optical parameters showed differences from conventional methods in predicting refractive outcome following PRK and revealed factors affecting image quality may account for some imperfections in visual performance based on simpler optical modeling.

Anterior Chamber

A new computer assisted objective method for quantifying vascular changes of the bulbar conjunctivae.

A novel computer software method was used to quantify the conjunctival plexus on the scleral background for measurement of the vascular surface area from photographs. A previously described method was used (Palmer, J. R., Owen, C. G., Ford, A. M., Jacobson, R. E. and Woodward, E. G. (1996). Optimal photographic imaging of the bulbar conjunctival vasculature. Ophthal. Physiol. Opt. 16, 144-149) to optimise photographic imaging of the bulbar conjuctival vasculature by increasing the information content in the image. Repeatability of this technique was evaluated. Twenty subjects (20 eyes) free from ophthalmological and systemic abnormality were examined on two separate occasions. The maximum 95% confidence limits for repeatability are +8.58/-3.95%. For 10 consecutive estimates of vascularity the maximum 95% confidence interval lie between +/- 6.54%. To evaluate the technique the lateral-bulbar conjunctivaein 10 soft (SCL) and 10 rigid gas permeable contact lens (RGPCL) wearers during the first 10 months of contact lens wear, were assessed and compared with subjective grading of hyperaemia. The new method showed sufficient sensitivity in detecting increased hyperaemia in the RGPCL wearing group and demonstrated statistically significant change. Subjective graded assessment of vascularity (using established classifications) detected increased hyperaemia, however, this was not statistically significant. Conjunctival vasculature is a dynamic structure and a source of valuable quantitative information where the ocular environment is varied, or where the ocular surface is affected by disease. Hence it is worthy of further investigation. A simple inexpensive method of computer assisted determination of vascularity is described.

Adult

Chromosome 19q cone-rod retinal dystrophy. Ocular phenotype.

OBJECTIVE: To describe the phenotype in a family with dominantly inherited cone-rod dystrophy with chromosome assignment to a 19q locus, and to correlate this with current classifications of this retinal dystrophy. DESIGN: A detailed clinical examination including Goldmann perimetry was undertaken in all family members. Six members under the age of 30 years underwent dark-adapted electroretinography, color contrast-sensitivity measurement, dark-adapted static perimetry, and dark adaptometry. PATIENTS: The study included 34 affected and 22 unaffected patients in four generations of a pedigree that manifested autosomal dominant cone-rod retinal dystrophy linked to a chromosome 19q locus by genetic linkage analysis. RESULTS: Loss of visual acuity occurred in the first decade of life, onset of night blindness occurred after 20 years of age, and little visual function remained after the age of 50 years. Central and, later, peripheral retinal fundus changes were associated with central scotoma, pseudoaltitudinal field defects, and finally global loss of function. Psychophysical and electrophysiologic testing before the age of 26 years showed more marked loss of cone than rod function. CONCLUSIONS: The phenotype associated with this mutation does not fit well into previous subtypes of cone-rod dystrophy. Further studies will be needed to correlate specific genetic mutations in this group of conditions with the various clinical phenotypes.

Adolescent

Autosomal dominant pattern dystrophy of the retina associated with a 4-base pair insertion at codon 140 in the peripherin/RDS gene.

OBJECTIVE: To define the phenotype of a retinal dystrophy associated with a 4-base pair insertion at codon 140 of the peripherin/RDS gene. PATIENTS: Six affected members spanning two generations of a single family were examined. Five were studied in detail electrophysiologically and psychophysically. METHODS: Psychophysical testing included color vision testing, photopic and scotopic static threshold perimetry, and dark adaptometry. Electrophysiological testing included flash and pattern electroretinography, as well as electrooculography. RESULTS: Clinical findings ranged from subtle pigmentary changes at the level of the retinal pigment epithelium to more widespread pigmentary changes associated with choroidal neovascularization. Those with severe fundus changes exhibited greater abnormalities in psychophysical and electrophysiological testing than those with minimal fundus changes. CONCLUSIONS: This particular peripherin/RDS gene mutation is associated with dominantly inherited pattern dystrophy of the retina. The phenotypic expression is variable in a manner not explained by age.

Aged

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 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