MyVisionTest News Archive
Jan 21, 2010
Progression of bilateral geographic atrophy
A new study finds that although the size of geographic atrophy may differ substantially between the eyes of persons with bilateral disease, the rate of progression of the two eyes is very similar.
Geographic atrophy (GA) occurs in the late-stage of dry AMD. It is the second most common cause of severe visual loss due to AMD, the most common being choroidal neovascularization. In individuals older than 85 years the prevalence of GA has recently been found to be four times higher than neovascular AMD. Studies suggest that 48% to 65% of prevalent cases involve bilateral GA.
GA is characterized by the development and gradual enlargement of uni- or multifocal atrophic patches that involve the retinal pigment epithelium as well as the corresponding neurosensory retina and choriocapillaris layer of the choroid. Areas of GA therefore correspond to absolute scotomas. Despite the recent breakthrough with anti-VEGF therapy for neovascular AMD, there is still no treatment available for patients with GA and no means to prevent or slow the progressive visual impairment. To develop new therapeutic interventions, a better understanding of the natural history and the underlying disease process appears mandatory.
Previous natural history studies have found considerable variability among patients with GA with regard to configuration, size, number, and spread of atrophic patches. In patients with bilateral GA, we have demonstrated a high degree of symmetry of fundus autofluorescence (FAF) patterns between the eyes of a patient in the presence of extensive interindividual variability. Furthermore, a positive correlation of size and configuration of atrophic patches and progression rates has been reported, whereas the correlation of visual acuity between the eyes was less pronounced.
Methods and Results
Analysis was performed in 156 eyes of 78 patients with bilateral GA. Best corrected visual acuity was determined with ETDRS charts. GA was quantified in digital fundus autofluorescence images (excitation, 488 nm; emission, >500 nm) by semiautomated imaging analysis. A linear, two-level, random-effects model was used to assess the natural course of disease. The concordance correlation coefficient (CCC) was calculated to assess the degree of agreement between disease characteristics of the left and right eyes. Bland-Altman plots were applied to compare measurements in the eyes.
CCC between the eyes was 0.310 for visual acuity, 0.706 for GA size, and 0.756 for GA progression rate. Although Bland-Altman plots revealed high concordance for the progression rate, there was considerable discrepancy between both eyes for GA.
Discussion and Conclusions
This study demonstrates that although the size of GA may differ substantially between the eyes of patients with bilateral GA, the progression rate represents a symmetrical process.
Although the size of GA between both eyes could differ substantially, there was a high degree of intraindividual symmetry in GA progression rate, which may indicate that specific disease mechanisms determine progression once GA has started. Although there was a high variability of disease progression among patients, genetic and/or environmental factors rather than nonspecific ageing processes may be considered as determinants for the rate of progression.
Potential risk factors on GA progression have been addressed in previous studies. Age, hypertension, diabetes, smoking history, or body mass index had no impact on enlargement rates of GA in previous studies. Although risk-variants of CFH, C3, and ARMS2 confer susceptibility for all AMD disease phenotypes including GA, a recent analysis showed that the risk alleles are not associated with GA progression over time.
It has been shown that the GA progression rate is fairly constant over time. Sunness et al. reported that knowledge of prior enlargement rate is predictive of subsequent enlargement rate. Furthermore, eyes with small areas tend to have a lower rate of enlargement compared to eyes with larger areas of GA. However, the dependence of the progression rate on the baseline size of GA was found to be less strong than the dependence on the prior progression rate.
In conclusion, the results indicate that GA spread in bilateral late atrophic AMD is a highly symmetrical process. Discrepancy in GA size may reflect an asymmetric onset of atrophic disease in affected individuals. A high degree of concordance in intraindividual disease progression in the presence of a high degree of interindividual variability would indicate an influence by individual characteristics rather than nonspecific ageing changes.
Read more...
Invest Ophthalmol Vis Sci. 2010 Feb;51(2):637-42
Tags: dry AMD
A new study finds that although the size of geographic atrophy may differ substantially between the eyes of persons with bilateral disease, the rate of progression of the two eyes is very similar.Geographic atrophy (GA) occurs in the late-stage of dry AMD. It is the second most common cause of severe visual loss due to AMD, the most common being choroidal neovascularization. In individuals older than 85 years the prevalence of GA has recently been found to be four times higher than neovascular AMD. Studies suggest that 48% to 65% of prevalent cases involve bilateral GA.
Previous natural history studies have found considerable variability among patients with GA with regard to configuration, size, number, and spread of atrophic patches. In patients with bilateral GA, we have demonstrated a high degree of symmetry of fundus autofluorescence (FAF) patterns between the eyes of a patient in the presence of extensive interindividual variability. Furthermore, a positive correlation of size and configuration of atrophic patches and progression rates has been reported, whereas the correlation of visual acuity between the eyes was less pronounced.
Methods and Results
Analysis was performed in 156 eyes of 78 patients with bilateral GA. Best corrected visual acuity was determined with ETDRS charts. GA was quantified in digital fundus autofluorescence images (excitation, 488 nm; emission, >500 nm) by semiautomated imaging analysis. A linear, two-level, random-effects model was used to assess the natural course of disease. The concordance correlation coefficient (CCC) was calculated to assess the degree of agreement between disease characteristics of the left and right eyes. Bland-Altman plots were applied to compare measurements in the eyes.
CCC between the eyes was 0.310 for visual acuity, 0.706 for GA size, and 0.756 for GA progression rate. Although Bland-Altman plots revealed high concordance for the progression rate, there was considerable discrepancy between both eyes for GA.
Discussion and Conclusions
This study demonstrates that although the size of GA may differ substantially between the eyes of patients with bilateral GA, the progression rate represents a symmetrical process.
Although the size of GA between both eyes could differ substantially, there was a high degree of intraindividual symmetry in GA progression rate, which may indicate that specific disease mechanisms determine progression once GA has started. Although there was a high variability of disease progression among patients, genetic and/or environmental factors rather than nonspecific ageing processes may be considered as determinants for the rate of progression.Potential risk factors on GA progression have been addressed in previous studies. Age, hypertension, diabetes, smoking history, or body mass index had no impact on enlargement rates of GA in previous studies. Although risk-variants of CFH, C3, and ARMS2 confer susceptibility for all AMD disease phenotypes including GA, a recent analysis showed that the risk alleles are not associated with GA progression over time.
It has been shown that the GA progression rate is fairly constant over time. Sunness et al. reported that knowledge of prior enlargement rate is predictive of subsequent enlargement rate. Furthermore, eyes with small areas tend to have a lower rate of enlargement compared to eyes with larger areas of GA. However, the dependence of the progression rate on the baseline size of GA was found to be less strong than the dependence on the prior progression rate.
In conclusion, the results indicate that GA spread in bilateral late atrophic AMD is a highly symmetrical process. Discrepancy in GA size may reflect an asymmetric onset of atrophic disease in affected individuals. A high degree of concordance in intraindividual disease progression in the presence of a high degree of interindividual variability would indicate an influence by individual characteristics rather than nonspecific ageing changes.
Read more...
Invest Ophthalmol Vis Sci. 2010 Feb;51(2):637-42
