Macular Degeneration: Dolar-Szczasny J

Dolar-Szczasny J, Mackiewicz J, Bindewald A, Holz FG, Zagórski Z. · Z Katedry i I Kliniki Okulistyki Akademii Medycznej w Lublinie. · Klin Oczna. · Pubmed #16417019 No free full text.

Abstract: PURPOSE: To present application of a confocal Scanning Laser Ophthalmoscope (cSLO) for fundus autofluorescence examination, as a new method of visualization of retinal pigment epithelium and its possible significance in the diagnosis of different retinal diseases. MATERIAL AND METHODS: Typical autofluorescence images in age-related macular degeneration (AMD), Stargardt disease, Best disease and pattern dystrophies are presented, based on the own experience and literature data. Autofluorescence images were obtained with a cSLO using an argon laser for generation of excitation light at 488 nm and a barrier filter >500 nm for the detection of the emitted signals. RESULTS: A variety of autofluorescence patterns, associated with the accumulation of lipofuscin in RPE cells, was found in the above entities. CONCLUSIONS: Presented method of fundus autofluorescence examination gives new possibilities in studying the pathogenetic mechanisms in various retinal diseases and may be useful in monitoring the follow-up and the effects of the treatment.

Dolar-Szczasny J, Mackiewicz J, Biziorek B, Zagórski Z. · Katedry i I Kliniki Okulistyki Akademii Medycznej w Lublinie. · Klin Oczna. · Pubmed #17725280 No free full text.

Abstract: PURPOSE: To identify patterns of fundus autofluorescence (AF) in patients with Stargardt dystrophy and fundus flavimaculatus. MATERIAL AND METHODS: 20 patients in age 7 to 47 years with Stargardt dystrophy and fundus flavimaculatus, were examined. Ophthalmic evaluation included nonstandarized Snellen visual acuity, complete ophthalmic examination, fluorescein angiography and color fundus photographs. The autofluorescence images were obtained using a confocal scanning laser ophthalmoscope HRA2. RESULTS: In 15 patients lack or decreased AF signal in a foveal region with punctate diffuse spots with increased and decreased AF signal extending far from the macular region were observed. In 4 patients apart from lack of the AF signal in the central area punctate spots were restricted to the macular region. In 1 patient AF image was copletely normal. CONCLUSIONS: Autofluorescence imaging allows for evaluation of the area with changes on the RPE level typical for this disease and is helpful, noninvasive examination for diagnostic process in such patients. A wide variation in clinical phenotype can occur in patients with Stargardt disease and fundus flavimaculatus. Obtained different phenotypes in autofluorescence imaging may correlate with different clinical types of this disease, described in the literature.

Mackiewicz J, Mańkowska A, Dolar-Szczasny J, Zubilewicz A, Oleszczuk A, Nowomiejska K, Rejdak R, Zagórski Z. · Katedry i I Kliniki Okulistyki Akademii Medycznej w Lublinie. · Klin Oczna. · Pubmed #17725273 No free full text.

Abstract: PURPOSE: To evaluate effects of intravitreal bevacizumab on visual acuity and angiographic lesions characteristics in patients with neovascular AMD and to report safety of such treatement. MATERIAL AND METHODS: 32 patients with confirmed choroidal neovascularisation (CNV) and AMD were treated. Patients received 2 intravitreal bevacizumabu (1.25 mg) iniections on 1-3 months basis. Control ophthalmic evaluations included visual acuity measurements with EDTRS charts, intraocular pressure measurements, complete ophthalmic examination in slit lamp, fluorescein angiography and blond pressure measurements. RESULTS: In 18 patients (56%) visual acuity improvement at a mean 3 lines on EDTRS charts was observed, in 9 patients (28%) visual acuity did not change and in 5 (16%) cases decreased visual acuity (about 1,5 lines in EDTRS charts) was noted. Mean follow-up period was 3 months after second injection. In most study eyes fluorescein angiography revealed a marked reduction in leakage from CNV. Apart from one case with endophthalmitis symptoms after second bevacizumab injection, we did not observed systemic or ocular adverse effects of the applied treatment. CONCLUSIONS: Short-term results suggest that intravitreal bevacizumab is relatively safe form of AMD treatement and is associated with improvement in visual acuity and reduction in angiographic leakage in most patients with neovascular AMD. Further evaluation of the long-term effectiveness of this treatment is warranted.

Dreyhaupt J, Dolar-Szczasny J, Bindewald A, Holz FG, Mansmann U. · Institute of Medical Biometry and Informatics, University of Heidelberg, INF 305, 69120 Heidelberg, Germany. · Methods Inf Med. · Pubmed #17694237 No free full text.

Abstract: OBJECTIVES: Identifying factors influencing the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). METHODS: Data on the natural course and suspected modifying factors were collected as part of the multicenter, longitudinal, observational FAM-study in 178 eyes of 114 patients with atrophic AMD. The endpoint of interest - the size of GA - was measured in fundus autofluorescence images. The influence of different putative risk factors on progression of GA is investigated with a forward selection procedure based on the likelihood ratio test. In order to interpret non-significant results of the forward selection procedure, the power of the tests used was quantified by a parametric post-hoc bootstrap approach. RESULTS: A mean increase in GA of 1.75 mm(2) per year was estimated for the given population (95% CI: [1.46; 2.02]). Patient and eye-specific random effects could be assessed. Neither patient-specific risk factors nor ocular-specific risk factors show any significant influence on GA growth. The post-hoc bootstrap procedure shows that only very strong effects can be detected on the basis of the given data. For example, the hypercholesteremia which would result in an additional increase of GA by near 4 mm(2) per year can be detected with a power of 80%. CONCLUSIONS: The use of linear mixed effects regression models offers a convenient way to explore sources of variation in the natural course of GA. Data from further follow-up examinations and data about other putative risk factors than those investigated will be needed to further investigate of the GA growth process. The procedure described in this article is easily applicable to other putative risk factors as well as to other fields of application.

Schmitz-Valckenberg S, Bindewald-Wittich A, Dolar-Szczasny J, Dreyhaupt J, Wolf S, Scholl HP, Holz FG, Anonymous00317. · Department of Ophthalmology, University of Bonn, Bonn, Germany, and First Eye Hospital, University of Lublin, Poland. · Invest Ophthalmol Vis Sci. · Pubmed #16723482 links to  free full text

Abstract: PURPOSE: To test the hypothesis that the extension of areas with increased fundus autofluorescence (FAF) outside atrophic patches correlates with the rate of spread of geographic atrophy (GA) over time in eyes with age-related macular degeneration (AMD). METHODS: The database of the multicenter longitudinal natural history Fundus Autofluorescence in AMD (FAM) Study was reviewed for patients with GA recruited through the end of August 2003, with follow-up examinations within at least 1 year. Only eyes with sufficient image quality and with diffuse patterns of increased FAF surrounding atrophy were chosen. In standardized digital FAF images (excitation, 488 nm; emission, >500 nm), total size and spread of GA was measured. The convex hull (CH) of increased FAF as the minimum polygon encompassing the entire area of increased FAF surrounding the central atrophic patches was quantified at baseline. Statistical analysis was performed with the Spearman's rank correlation coefficient (rho). RESULTS: Thirty-nine eyes of 32 patients were included (median age, 75.0 years; interquartile range [IQR], 67.8-78.9); median follow-up, 1.87 years; IQR, 1.43-3.37). At baseline, the median total size of atrophy was 7.04 mm2 (IQR, 4.20-9.88). The median size of the CH was 21.47 mm2 (IQR, 15.19-28.26). The median rate of GA progression was 1.72 mm2 per year (IQR, 1.10-2.83). The area of increased FAF around the atrophy (difference between the CH and the total GA size at baseline) showed a positive correlation with GA enlargement over time (rho=0.60; P=0.0002). CONCLUSIONS: FAF characteristics that are not identified by fundus photography or fluorescein angiography may serve as a prognostic determinant in advanced atrophic AMD. As the FAF signal originates from lipofuscin (LF) in postmitotic RPE cells and since increased FAF indicates excessive LF accumulation, these findings would underscore the pathophysiological role of RPE-LF in AMD pathogenesis.

Dreyhaupt J, Mansmann U, Pritsch M, Dolar-Szczasny J, Bindewald A, Holz FG. · Department of Medical Biometry and Informatics, University of Heidelberg, Germany. · Ophthalmic Epidemiol. · Pubmed #16283987 No free full text.

Abstract: PURPOSE: To model the natural course of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). METHODS: Data on the natural course of GA were collected in the multi-center, longitudinal, prospective observational FAM study. The size of GA was measured by autofluorescence scanning laser ophthalmoscopy. The natural course of GA is modelled by two different mixed effect models (MEM). Both models are compared with respect to the correctness of the model assumptions, goodness of fit, and predictive behavior. RESULTS: The linear model results in better prediction, the non-linear model is more in agreement with the model assumptions. The non-linear model fits the data for small and large areas of GA better, while the linear model seems to be more adequate for the medial areas. More data will be needed to study the interplay of both models in more detail. CONCLUSIONS: The natural course of GA varies extremely between individuals. However, reliable factors for the explanation of this variability have so far not been established. MEM are useful for describing "inter-individual" as well as "intra-individual" influences without the need for precise knowledge of the influencing factors. Using MEM to evaluate data on the natural history of GA allows one to derive parameter estimates, which could be used to design interventional trials for modes of therapy with a potential to reduce or stop the progression of GA in patients with AMD.

Bindewald A, Bird AC, Dandekar SS, Dolar-Szczasny J, Dreyhaupt J, Fitzke FW, Einbock W, Holz FG, Jorzik JJ, Keilhauer C, Lois N, Mlynski J, Pauleikhoff D, Staurenghi G, Wolf S. · Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, 53127 Bonn, Germany. · Invest Ophthalmol Vis Sci. · Pubmed #16123434 links to  free full text

Abstract: PURPOSE: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in eyes with early nonexudative age-related macular disease (AMD). METHODS: FAF images were recorded in eyes with early AMD by confocal scanning laser ophthalmoscopy (cSLO) with excitation at 488 nm (argon or OPSL laser) and emission above 500 or 521 nm (barrier filter). A standardized protocol for image acquisition and generation of mean images after automated alignment was applied, and routine fundus photographs were obtained. FAF images were classified by two independent observers. The kappa statistic was applied to assess intra- and interobserver variability. RESULTS: Alterations in FAF were classified into eight phenotypic patterns including normal, minimal change, focal increased, patchy, linear, lacelike, reticular, and speckled. Areas with abnormal increased or decreased FAF signals may or may not have corresponded to funduscopically visible alterations. For intraobserver variability, kappa of observer I was 0.80 (95% confidence interval [CI]0.71-0.89) and of observer II, 0.74. (95% CI, 0.64-0.84). For interobserver variability, kappa was 0.77 (95% CI, 0.67-0.87). CONCLUSIONS: Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast to a nonspecific aging process. The results indicate that the classification system yields a relatively high degree of intra- and interobserver agreement. It may be applicable for determination of novel prognostic determinants in longitudinal natural history studies, for identification of genetic risk factors, and for monitoring of future therapeutic interventions to slow the progression of early AMD.

Bindewald A, Schmitz-Valckenberg S, Jorzik JJ, Dolar-Szczasny J, Sieber H, Keilhauer C, Weinberger AW, Dithmar S, Pauleikhoff D, Mansmann U, Wolf S, Holz FG. · Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, D-53127 Bonn, Germany. · Br J Ophthalmol. · Pubmed #15965170 links to  free full text

Abstract: AIM: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in the junctional zone of geographic atrophy (GA) in patients with age related macular degeneration. METHODS: Digital FAF images were recorded in 164 eyes of 107 patients using a confocal scanning laser ophthalmoscope (cSLO; excitation 488 nm, detection above 500 nm) as part of a prospective multicentre natural history study (FAM Study). FAF images were obtained in accordance with a standardised protocol for digital image acquisition and generation of mean images after automated alignment. RESULTS: Image quality was sufficient for classification of FAF patterns in 149 eyes (90.9%) with lens opacities being the most common reason for insufficient image quality. Abnormal FAF outside GA in 149 eyes was classified into four patterns: focal (12.1%), banded (12.8%), patchy (2.0%), and diffuse (57.0%), whereby 12.1% had normal background FAF in the junctional zone. In 4% there was no predominant pattern. The diffuse pattern was subdivided into four groups including reticular (4.7%), branching (27.5%), fine granular (18.1%), and fine granular with peripheral punctate spots (6.7%). CONCLUSIONS: Different phenotypic patterns of abnormal FAF in the junctional zone of GA can be identified with cSLO FAF imaging. These distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast with a non-specific ageing process. A refined phenotypic classification may be helpful to identify prognostic determinants for the spread of atrophy and visual loss, for identification of genetic risk factors as well as for the design of future interventional trials.