Macular Degeneration: Unnebrink K

Staudt S, Miller DW, Unnebrink K, Holz FG. · Universitäts-Augenklinik, Heidelberg, Germany. · Ophthalmologe. · Pubmed #14504894 No free full text.

Abstract: PURPOSE. In the majority of patients with full-thickness macular hole, closure can be achieved with vitreoretinal surgery techniques. However, postoperative function is variable and the prognostic determinants for visual acuity are incompletely understood. We evaluated the incidence and extent of macular edema after macular foramen surgery with and without combined cataract-surgery. METHODS. Between October 1997 and March 2001 macular foramen surgery was performed in 125 eyes from 116 patients. Fluorescein angiograms with sufficient quality were obtained from 59 eyes using a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph, HRA, Heidelberg Engineering, Heidelberg) and were evaluated by two independent observers. RESULTS. Angiographic macular edema was noted on average 4.2 months after the operation in 47 out of 59 (79.7%) eyes. The incidence of macular edema was 87% in eyes after a combined cataract operation compared to 66.7 % in eyes with no simultaneous operation ( p=0.735). Mean postoperative visual acuity was 0.4 (min 0.1-max 1.2) with no significant difference between eyes with (4.1 lines) and without macular edema (3.5 lines) with regard to visual improvement from baseline. CONCLUSIONS. The results indicate a high incidence of macular edema in eyes after macular hole surgery with subsequent anatomical success. Apparently, the presence of macular edema is not associated with short term visual impairment. Furthermore it seems that a combined cataract operation compared to a consecutive procedure is not associated with disadvantages regarding the functional outcome.

Bellmann C, Unnebrink K, Rubin GS, Miller D, Holz FG. · Department of Ophthalmology, University of Heidelberg, INF 400, 69120 Heidelberg, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #13680248 No free full text.

Abstract: BACKGROUND: Patients with advanced age-related macular degeneration (AMD) suffer not only from impairment in central visual acuity (VA), but also from reduction in contrast sensitivity (CS). We examined VA and CS changes over time in patients with subfoveal choroidal neovascularizations (CNV) as well as the correlation between the two parameters. METHODS: VA was determined according to a standardized protocol with the Early Treatment Diabetic Retinopathy (ETDRS) chart. CS was measured with Pelli-Robson charts. The angiographic characteristics of CNV and the presence of CNV in the fellow eye as well as gender and age were evaluated as possible prognostic factors of VA and CS progression. Two hundred and five patients with neovascular AMD were recruited within the Radiation Therapy for Age-Related Macular Degeneration (RAD) Study and were reviewed over 2 years. The treatment and control groups showed no significant difference for VA or for CS ( P>0.05), and both groups were considered together. RESULTS: At baseline, mean VA was 55.6+/-14.5 SD letters (EDTRS chart), and mean CS was 22.8+/-6.9 letters (Pelli-Robson chart). Spearman Correlation Coefficient ( r(s)) between VA and CS was r(s)=0.60, P=0.0001. Over 2 years the mean VA loss was 23.6+/-21.4 letters and mean CS reduction was 9.0+/-9.7 letters. Agreement between change of VA and change of CS was moderate ( r(s)=0.65, P=0.0001; kappa coefficient (grouped into VA loss < or =15, >15, >30 letters; CS loss < or =6, >6, >15 letters) kappa=0.43, 95% CI [0.32;0.54]). Proportional hazard models did not show any apparent influence of type of CNV, or CNV in the fellow eye, on change in VA and CS. CONCLUSION: The results indicate that VA and CS do not always show the same progression in visual function loss although they show a moderate correlation in eyes with neovascular AMD. Both parameters provide important information about visual disability and should be evaluated as outcome in interventional studies.

Holz FG, Jorzik J, Schutt F, Flach U, Unnebrink K. · Department of Ophthalmology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. · Ophthalmology. · Pubmed #12578787 No free full text.

Abstract: OBJECTIVE: To determine intraobserver and interobserver variation for classifying types of choroidal neovascularizations (CNV) in exudative age-related macular degeneration (ARMD). DESIGN: Intraexaminer and interexaminer reliability study. PARTICIPANTS: Digital high-quality fluorescein angiograms of 40 patients with neovascular ARMD were evaluated independently by 16 retinal specialists. MAIN OUTCOME MEASURES: Fluorescein angiographies were presented in two randomized sequences (series A and B) to each masked reader for classification of type of CNV into classic, occult, or mixed with classic component of less or greater 50%. Agreement was evaluated by calculating kappa statistics (kappa) and intraclass correlation coefficients. RESULTS: The mean kappa coefficient was 0.64 +/- 0.11 for intraobserver variation, with a range from 0.44 to 0.89. For interobserver variation the intraclass correlation coefficients was calculated as 0.66 (95% confidence interval [CI] 0.56, 0.77) for series A and as 0.55 (95% CI 0.43, 0.67) for series B. CONCLUSIONS: Angiographic classification of CNV secondary to ARMD can vary considerably not only between observers but also for repeated evaluation by the same observer. Because various current and emerging treatments including photodynamic therapy are based on specific angiographic characteristics, accurate interpretation will become more important.

Schmitz-Valckenberg S, Jorzik J, Unnebrink K, Holz FG, Anonymous00191. · Department of Ophthalmology, University of Heidelberg, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #11933894 No free full text.

Abstract: BACKGROUND: Fundus autofluorescence (AF) imaging using confocal scanning laser ophthalmoscopy (cSLO) has been shown to be superior to fundus photography or angiography for delineating areas of geographic atrophy (GA) in retinal pigment epithelium (RPE) and for recording variation over time. We have evaluated a method for automated computerized detection and quantitation of RPE atrophy. METHODS: AF images in vivo were recorded with a confocal scanning laser ophthalmoscope (exc. 488 nm, em. >500 nm; Heidelberg Retina Angiograph). The intensity of AF in atrophic areas was markedly decreased. Two independent readers analysed these areas in 24 right eyes manually by outlining GA areas using a mouse-driven arrow (method A) and automatically by image analysis software (Global Lab Image/2) after subjective adjustment of thresholding (method B). Agreement between observers and between methods A and B was assessed by the Bland-Altman design for method-comparison studies. RESULTS: Larger areas were measured using method A than B by both readers (agreement A/B: reader 1 mean difference 1.04 mm, 95% CI [0.66,1.42]; reader 2 mean difference 0.62 mm, 95% CI [0.43,0.81]). The agreement between the readers was mean difference 0.39 mm (95% CI [0.02,0.76]) for A and mean difference -0.03 mm (95% CI [-0.23,0.18]) for B. Features making the delineation of borders of GA difficult included large choroidal vessels with autofluorescent properties in the GA area and media opacities. CONCLUSIONS: Fundus AF cSLO imaging provides a reliable means to delineate areas of GA. The automated image analysis allows more accurate detection and quantitative documentation of atrophic areas than manual outlining. This method will be useful in longitudinal natural history studies and for monitoring effects of future therapeutic interventions to slow down GA progression in patients with advanced atrophic ARMD and other retinal diseases associated with outer retinal atrophy.

Bellmann C, Miller DW, Mehltretter K, Schütt F, Jorzik J, Unnebrink K, Holz FG. · Department of Ophthalmology, University of Heidelberg, Germany. · Br J Ophthalmol. · Pubmed #12812893 links to  free full text

Abstract: BACKGROUND/AIMS: To document the natural history and to assess the efficacy of interventional therapies in neovascular age related macular degeneration (AMD), an accurate and reproducible method is required for analysis of consecutive fluorescence angiograms. The development and evaluation of an image analysis software for this purpose is described here. It allows for the quantitative analysis of changes in CNV and/or leakage area over time. METHODS: In digitised angiograms, a mouse driven arrow was used to delineate the CNV border. The ratio of the CNV area to the square of the distance between two vessels was automatically calculated by pixel count to compensate for variation in image sizes at different examination times. These results were directly transferred and stored in a database. To assess reproducibility, CNV areas in 20 patients with occult and 20 patients with classic CNV were determined independently by two readers. RESULTS: There was only marginal variability between observers with this method: the mean deviation was 0.01 pixels for classic CNV (95% CI -0.17 to +0.15, SD 0.35) and 0.55 pixels for occult CNV (95% CI -1.06 to -0.04, SD 1.14). CONCLUSIONS: This practical PC based method allows for quantification of angiographic features such as CNV size in early frames and area of leakage in late frames. Limitations include non-readily defined borders in angiograms of poor image quality or indistinct borders of the hyperfluorescent areas of interest. The software is applicable to future clinical trials where the analysis of neovascular complex changes is required, for example, following therapeutic intervention.

Bellmann C, Jorzik J, Spital G, Unnebrink K, Pauleikhoff D, Holz FG. · Department of Ophthalmology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. · Arch Ophthalmol. · Pubmed #12003606 No free full text.

Abstract: BACKGROUND: As a cause for severe visual loss, geographic atrophy of the retinal pigment epithelium is about half as common as choroidal neovascularization in patients with advanced age-related macular degeneration. To assess symmetry, we determined intraindividual variations of various features of bilateral geographic atrophy in patients with atrophic age-related macular degeneration in a cross-sectional study. METHODS: Patients were examined with the use of a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph; Heidelberg Engineering, Heidelberg, Germany). Digital infrared reflection images (excitation, 830 nm) and fundus autofluorescence images (excitation, 488 nm) were recorded. The eyes of each patient were compared regarding number, size, and convex hull of the atrophic areas with the use of image analysis software and with respect to fundus autofluorescence changes in the junctional zone. RESULTS: Seventy-two patients (mean +/- SD age, 76.3 +/- 7.9 years) were examined. The number of atrophic areas ranged from 1 to 23 (mean +/- SD, 4.9 +/- 4.6); the size of geographic atrophy, from 0.18 to 30.20 (mean +/- SD, 7.0 +/- 6.6) mm(2); and the size of the convex hull, from 0.18 to 39.20 (mean +/- SD, 11.7 +/- 8.4) mm(2). No statistically significant difference was found when comparing these variables between each left and right eye: number, P =.62; size, P =.81; and convex hull, P =.78. Identical patterns of fundus autofluorescence were observed in 43 (80%) of 54 patients. CONCLUSIONS: There is intraindividual symmetry in eyes with bilateral geographic atrophy in the presence of a wide range of interindividual variability. The findings are in accordance with the view that age-related macular degeneration is not merely the result of a nonspecific aging process. Symmetric manifestations, rather, reflect specific individual determinants in the pathogenesis and manifestation of the disease.