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Biomedical subjects

Fred W Fitzke

Publications and source records attributed to Fred W Fitzke.

10 recordsLinked to original sources
PubMed2006

Assessment of neuroprotective effects of glutamate modulation on glaucoma-related retinal ganglion cell apoptosis in vivo.

PURPOSE: To assess the neuroprotective effects of different glutamate modulation strategies, with a nonselective (MK801) and a selective (ifenprodil) NMDA receptor antagonist and a metabotropic glutamate receptor agonist (mGluR Group II, LY354740), in glaucoma-related in vivo rat models of retinal ganglion cell (RGC) apoptosis. METHODS: RGC apoptosis was induced in Dark Agouti (DA) rats by staurosporine (SSP) treatment. Single agents MK801, ifenprodil, or LY354740, or MK801 and LY354740 combined, were administrated intravitreally at different doses. Eyes were imaged in vivo using a recently established technique and the results confirmed histologically. The most effective combined therapy regimen of MK801 and LY354740 was then assessed in a chronic ocular hypertension (OHT) rat model with application at 0, 1, and 2 weeks after OHT surgery and the effects assessed as described before. RESULTS: All strategies of glutamate modulation reduced SSP-induced-RGC apoptosis compared with the control, in a dose-dependent manner: MK801 (R2= 0.8863), ifenprodil (R2= 0.4587), and LY354740 (R2= 0.9094), with EC50s of 0.074, 0.0138, and 19 nanomoles, respectively. The most effective combination dose of MK801 and LY354740 was 0.06 and 20 nanomoles (P < 0.05), respectively, and the optimal timing of the therapy was 0 weeks after OHT surgery (P < 0.05). CONCLUSIONS: This novel SSP model was validated as a useful tool for screening neuroprotective strategies in vivo. Group II mGluR modulation may be a useful treatment for RGC death. Combination therapy optimized to limit neurotoxic effects of MK801 may be an effective neuroprotective approach in retinal degenerative disease. Furthermore, treatments that minimize secondary RGC degeneration may be most useful in glaucoma.

Animals↗
PubMed2006

Maculopathy due to the R345W substitution in fibulin-3: distinct clinical features, disease variability, and extent of retinal dysfunction.

PURPOSE: To determine (1) clinical features that distinguish maculopathy due to the R345W substitution in fibulin-3 from other forms of inherited or early-onset drusen, (2) the phenotypic variability, and (3) the extent of retinal disease in those with a positive molecular diagnosis. METHODS: Affected individuals underwent ophthalmic examination, digital color fundus photography, fundus autofluorescence (AF) imaging, and psychophysical testing with automated photopic and dark-adapted perimetry and fine matrix mapping. Blood samples were taken for DNA extraction and screening for the R345W mutation in fibulin-3. Patients were subsequently divided into mutation-positive and -negative groups, to compare the identified phenotypic findings in these two sets of subjects. RESULTS: Twenty-nine subjects from 19 families were ascertained with inherited or early-onset drusen. Twenty-four (83%) subjects from 15 families were found to harbor the R345W fibulin-3 mutation. Peripapillary deposition and a radial distribution of macular drusen were consistent, distinguishing signs in the mutation-positive group. Subretinal neovascular membrane (SRNVM) was a rare occurrence, affecting only 1 of 48 eyes, whereas hyperpigmentation and atrophy of the retinal pigment epithelium (RPE) were common in older mutation-positive patients. Increased AF corresponding to the drusen was detected in both the mutation-positive and -negative groups. The phenotype in the group of patients positive for the R345W mutation was extremely variable, with evidence of interocular, intrafamilial, and interfamilial variability in visual loss, natural history, ophthalmoscopic findings, autofluorescence imaging, and psychophysical data. The novel finding of nonpenetrance was observed in a 62-year-old asymptomatic, mutation-positive man. The findings from detailed perimetry performed on a subset of subjects were consistent with the presence of widespread retinal dysfunction not isolated to the macula. CONCLUSIONS: Marked inter- and intrafamilial variation associated with the fibulin-3 R345W mutation in terms of retinal appearance, severity, progression, and nonpenetrance were identified. It was noted that SRNVM is a rare occurrence in R345W fibulin-3 maculopathy. These findings are helpful for advice regarding prognosis and for genetic counseling. The findings established that the presence of peripapillary deposit is highly likely to indicate that a patient carries the R345W mutation.

Adult↗
PubMed2005

Autofluorescence imaging of choroidal neovascularization due to age-related macular degeneration.

OBJECTIVE: To describe the autofluorescence (AF) characteristics of choroidal neovascularization (CNV) in patients with age-related macular degeneration. METHODS: Autofluorescence images of 65 consecutive eyes with CNV at various stages of evolution were analyzed. Twenty images were of recent-onset CNV (group 1), 8 were of eyes 1 to 6 months after CNV diagnosis (group 2), and 37 were late-stage CNV (group 3). Autofluorescence images from groups 1 and 2 were compared with fundus fluorescein angiographic images. RESULTS: Group 1 showed areas of hyperfluorescence on fundus fluorescein angiography corresponding to areas of normal AF in 16 of 20 cases, with adjacent areas of increased AF in 13 cases. The main areas of abnormal AF were larger than the main areas of abnormal fluorescence on fundus fluorescein angiography in 18 of the 20 cases. Groups 2 and 3 showed areas of decreased AF corresponding to areas of previous leakage on fundus fluorescein angiography (in group 2) or atrophy. CONCLUSIONS: Preserved AF in group 1 indicates viable retinal pigment epithelium initially, which has implications for visual prognosis. Decreased AF in groups 2 and 3 indicates loss of retinal pigment epithelium and photoreceptors. Autofluorescence imaging may increase our understanding of CNV in age-related macular degeneration.

Aged↗
PubMed2004

Reducing noise in suspected glaucomatous visual fields by using a new spatial filter.

Visual field testing with automated perimetry is hampered by the amount of noise present in the readings. Here, we derive a physiologically accurate spatial filter to be applied to the data after patient examination. The filter was tested by a Virtual Eye computer simulation. By simulating series of stable fields it was shown that specificity of determining visual field changes was improved; while simulating progressing fields (based on a map of the optic nerve head) it was shown that sensitivity was also improved. The filter appears to reduce the noise in glaucomatous visual field data and may be clinically useful.

Computer Simulation↗
PubMed2004

Magnification changes in scanning laser tomography.

PURPOSE: It is important when evaluating glaucomatous optic disc progression in longitudinal images that image magnification remains unchanged. We studied the effect of changed lens power on magnification in scanning laser tomography. The relative contribution to magnification of axial length, eye-scanner distance, and image-to-image scaling was also assessed. METHODS: A simulated optic disc in a model eye was imaged using the Heidelberg Retina Tomograph. Lens power was alterable by exchanging intraocular lenses (IOL) mounted at the lens plane of the eye to mimic changes in the crystalline lens. IOL power of +20.0D and axial length of 21.5 mm was compatible with emmetropia. The optic disc was imaged through IOLs differing in power (+16.0D to +25.0D) but with axial length kept constant. IOL power was then held constant and imaging was repeated for various axial lengths (17.5-23.5 mm). Model eye-scanner distance was varied with each test sequence. The distances between landmarks on the disc was measured before and after contour lines were exported. RESULTS: Image size varied with IOL power and axial length (r > 0.98; P < 0.0001), with the magnification effect of a +1D increase in lens power equivalent to a third the magnification effect of a 1-mm increase in axial length. Magnification tended to increase with myopia (IOL power > +20.0D) and was accentuated by longer eye-scanner distances. Image-to-image scaling corrected some magnification though this varied with ametropia. CONCLUSIONS: Changed lens power, axial length, and eye-scanner distance can affect the size of the optic disc in scanning laser tomography images. The exported contour line partly compensates for changed magnification.

Disease Progression↗
PubMed2003

Macular pigment density and distribution: comparison of fundus autofluorescence with minimum motion photometry.

Macular pigment (MP) distribution profiles were measured for 18 subjects using a Moreland anomaloscope modified for motion photometry. The total amount of MP within the central 7 degrees was estimated from the distribution profile by numerical integration. Fundus autofluorescence images were obtained for eight of these subjects using a scanning laser ophthalmoscope. Peak optical density of MP increased with the total amount present, but the correlation was weakened by inter-subject differences in MP distribution. The mean MP distribution derived from mean grey-scale profiles of fundus autofluorescence images correlated closely with that obtained psychophysically (r=0.96). Autofluorescence imaging provides a fast non-invasive method for assessing MP in vivo.

Aging↗
PubMed2003

Reasons for rim area variability in scanning laser tomography.

PURPOSE: To determine reasons for rim area variability in scanning laser tomography. METHODS: Regional rim area variability from testing in same and different visits and by same and different observers was characterized in 30 normal and 42 glaucomatous eyes. Variations in (1) optic nerve head (ONH) surface geometry (center of gravity: X, Y, Z), (2) image tilting (horizontally and vertically), and (3) position of the reference plane in relation to the ONH (REF) were analyzed by multiple regression analysis. Whether and how much these factors explain rim area variability was studied in cross-sectional and longitudinal data by using two different reference planes. RESULTS: Variability was higher in glaucoma and in testing by different observers in separate visits. Across a range of eyes, approximately 40% of variability in single-topography images and 60% of variability in mean-topography images was explained. In individual image series, a median 85% of variability was explained, exceeding 90% in at least 25% of eyes. The most frequent contributors to rim area variability were REF (in > or =95%) and Z (in > or =80%); they also usually explained more variability than other factors. The nature of variability differed between reference planes. CONCLUSIONS: A large proportion of rim area variability was explained by variation in the topographical features studied, especially REF and Z. Reference plane definition also influenced variability. Variation in the position of the reference plane in relation to the ONH can affect rim area measurements and should be considered when evaluating the progression of glaucoma.

Aged↗
PubMed2003

How sensitive to clinical change are ETDRS logMAR visual acuity measurements?

PURPOSE: To determine the sensitivity to change and specificity achieved when published test-retest variability (TRV) data are used to determine whether measured changes in ETDRS logarithm of the minimum angle of resolution (logMAR) visual acuity reflect true clinical change or are attributable to measurement error alone. METHODS: Various degrees of change in visual acuity were simulated in a group of normal subjects by adjusting test difficulty through manipulation of viewing distance. Sensitivity to simulated change and specificity were determined with change criteria derived from published Bland-Altman 95% ranges for TRV. RESULTS: The relationship between viewing distance and measured acuity was as predicted theoretically. Simulated acuity change of 0.2 logMAR (two lines of letters) or greater can be reliably distinguished from no change (both sensitivity and specificity >95%) with the ETDRS chart, but a change of 0.1 logMAR or less cannot. CONCLUSIONS: The use of 95% ranges for TRV to establish the smallest measured visual acuity change that can be reliably detected ensures a high specificity but does not take account of sensitivity. Use of change criteria derived from published 95% ranges results in a sensitivity of approximately 50% (assuming identical levels of TRV). Sensitivity may be improved by using a change criterion that is smaller than the minimum change sought, providing the change criterion is still at least as large as the 95% range for TRV, so that specificity is maintained. Reducing TRV allows smaller changes in acuity to be reliably detected.

Humans↗
PubMed2002

Relationship between electrophysiological, psychophysical, and anatomical measurements in glaucoma.

PURPOSE: To evaluate the relationship between electrophysiological, psychophysical, and structural measurements in normal and glaucomatous eyes and to test the hypothesis that there is a continuous structure-function relationship between ganglion cell numbers and visual field sensitivity. METHODS: Thirty-four normal subjects and 40 patients with glaucoma were examined with the pattern electroretinogram (PERG), perimetry and retinal tomography. Transient and steady state (SS) PERGs were recorded, and peak (P)-to-trough (N) amplitude was measured. The unit of differential light sensitivity (DLS) in perimetry is the decibel. The decibel is 10. log(1/Lambert), where the Lambert is the unit of test spot intensity. PERG amplitudes were correlated with decibel and 1/Lambert DLS for the central 18 degrees of the visual field and with neuroretinal rim area in the temporal part of the optic disc. Age-related changes in the structural and functional measurements were sought. The correlation between variables was investigated by linear and quadratic regression analysis. A quadratic (y = ax + bx(2) + c) fit was taken to be significantly better than a linear fit, if the coefficient (b) for the x(2) term was significant at P < 0.05. RESULTS: A quadratic fit between decibel DLS and PERG amplitude (transient PERG: R(2) = 0.40, P = 0.0000; SS PERG: R(2) = 0.32, P = 0.0000) was significantly better than a linear fit. There was a linear correlation between 1/Lambert DLS and PERG amplitude (transient PERG: R(2) = 0.44, P = 0.0000; SS PERG: R(2) = 0.35, P = 0.0000). There was a linear correlation between temporal neuroretinal rim area and PERG amplitude (transient PERG: R(2) = 0.17, P = 0.0003; SS PERG: R(2) = 0.20, P = 0.0001). A quadratic fit between decibel DLS and temporal neuroretinal rim area (R(2) = 0.38, P = 0.0000) was significantly better than a linear fit. There was a linear correlation between 1/Lambert DLS and temporal neuroretinal rim area (R(2) = 0.30, P = 0.0000). Both DLS and PERG amplitude declined with age in the normal subjects. The rate of decline was -0.17%, -0.74%, -0.75%, and -0.78% per year for decibel DLS, 1/Lambert DLS, transient PERG, and SS PERG, respectively. CONCLUSIONS: There is a curvilinear relationship between decibel DLS and both PERG amplitude and neuroretinal rim area, and a linear relationship between 1/Lambert DLS and PERG amplitude and neuroretinal rim area. These findings support the hypothesis that there is no ganglion cell functional reserve but a continuous structure-function relationship, and that the impression of a functional reserve results from the logarithmic (decibel) scaling of the visual field.

Aged↗