Tracking progression with spectral-domain optical coherence tomography in geographic atrophy caused by age-related macular degeneration.

PURPOSE To investigate, with the use of spectral-domain optical coherence tomography (SD-OCT), microstructural alterations over time in eyes with progressive geographic atrophy (GA) due to age-related macular degeneration. METHODS Forty-six eyes of 26 patients (median age, 77.9 years [interquartile range (IQR), 71.8-81.0]) with GA without evidence of active or previous neovascular disease at baseline were examined by simultaneous confocal scanning laser ophthalmoscopy (cSLO) and SD-OCT. Serial examinations with alignment of follow-up to baseline scans were performed over a median period of 12.2 months (IQR, 10.2-15.3). Longitudinal SD-OCT variations were evaluated, including quantification of retinal thickness (RT) change and lateral spread of GA (LSGA) at a temporal, nasal, inferior, and superior GA border-section in each eye. RESULTS GA-enlargement was characterized by progressive loss of the outer hyperreflective SD-OCT bands and by thinning of the outer nuclear layer with subsequent approach of the outer plexiform layer toward Bruch's membrane. In the perilesional zone, various dynamic changes were recorded, including migration of hyperreflective material and changes in drusen height. At the borders, there was a median RT change of -14.09 microm/y (IQR -26.21 to -7.48 microm/y). The median LSGA was 106.90 microm/y (IQR, 55.44-161.70 microm/y). Both parameters showed only moderate intraocular agreement (RT change: intraclass correlation coefficient [ICC], 0.54; 95% CI, 0.39-0.67; LSGA: ICC, 0.49; 95% CI, 0.34-0.64) and no statistical significant difference for one location (RT change, P = 0.125; LSGA, P = 0.516; likelihood ratio test). CONCLUSIONS Combined cSLO and SD-OCT imaging provides unprecedented insight into dynamic microstructural changes of GA enlargement that may help to better understand the pathogenesis of the disease. Quantitative progression data indicate local factors may exist that drive progression in junctional areas (ClinicalTrials.gov number, NCT00393692).

[1]  Jens Dreyhaupt,et al.  Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. , 2007, American journal of ophthalmology.

[2]  Ronald Klein,et al.  Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. , 2007, Ophthalmology.

[3]  J S Sunness,et al.  The natural history of geographic atrophy, the advanced atrophic form of age-related macular degeneration. , 1999, Molecular vision.

[4]  P. D. de Jong,et al.  Cigarette smoking and age-related macular degeneration in the EUREYE Study. , 2007, Ophthalmology.

[5]  Albert Hofman,et al.  Epidemiology of age-related maculopathy: a review. , 2003, European journal of epidemiology.

[6]  U. Mansmann,et al.  Automated analysis of digital fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration using confocal scanning laser ophthalmoscopy (cSLO) , 2005, BMC ophthalmology.

[7]  J S Sunness,et al.  Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration. , 1999, Ophthalmology.

[8]  Steffen Schmitz-Valckenberg,et al.  High-resolution spectral domain-OCT imaging in geographic atrophy associated with age-related macular degeneration. , 2008, Investigative ophthalmology & visual science.

[9]  Frederick L Ferris,et al.  Change in area of geographic atrophy in the Age-Related Eye Disease Study: AREDS report number 26. , 2009, Archives of ophthalmology.

[10]  C Bellman,et al.  Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. , 2001, Investigative ophthalmology & visual science.

[11]  Eyal Margalit,et al.  The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials. , 2007, Ophthalmology.

[12]  Thomas S Hwang,et al.  Retinal precursors and the development of geographic atrophy in age-related macular degeneration. , 2008, Ophthalmology.

[13]  Robert F. Mullins,et al.  An Integrated Hypothesis That Considers Drusen as Biomarkers of Immune-Mediated Processes at the RPE-Bruch's Membrane Interface in Aging and Age-Related Macular Degeneration , 2001, Progress in Retinal and Eye Research.

[14]  William R. Freeman,et al.  Correlation between spectral-domain optical coherence tomography and fundus autofluorescence at the margins of geographic atrophy. , 2009, American journal of ophthalmology.

[15]  Neil M Bressler,et al.  DESIGNING CLINICAL TRIALS FOR AGE-RELATED GEOGRAPHIC ATROPHY OF THE MACULA: Enrollment Data From the Geographic Atrophy Natural History Study , 2006, Retina.

[16]  Monika Fleckenstein,et al.  Clinical evaluation of simultaneous confocal scanning laser ophthalmoscopy imaging combined with high‐resolution, spectral‐domain optical coherence tomography , 2010, Acta ophthalmologica.

[17]  Usha Chakravarthy,et al.  Prevalence of age-related maculopathy in older Europeans: the European Eye Study (EUREYE). , 2006, Archives of ophthalmology.

[18]  D. S. Mcleod,et al.  Quantifying changes in RPE and choroidal vasculature in eyes with age-related macular degeneration. , 2002, Investigative ophthalmology & visual science.

[19]  C. Keilhauer,et al.  Classification of abnormal fundus autofluorescence patterns in the junctional zone of geographic atrophy in patients with age related macular degeneration , 2005, British Journal of Ophthalmology.

[20]  W R Green,et al.  Senile macular degeneration: a histopathologic study. , 1977, Transactions of the American Ophthalmological Society.

[21]  Wolfgang Drexler,et al.  Cellular and functional optical coherence tomography of the human retina: the Cogan lecture. , 2007, Investigative ophthalmology & visual science.

[22]  J. Izatt,et al.  Spectral domain optical coherence tomography imaging of geographic atrophy margins. , 2009, Ophthalmology.

[23]  F. Holz,et al.  Analysis of digital scanning laser ophthalmoscopy fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration , 2002, Graefe's Archive for Clinical and Experimental Ophthalmology.

[24]  S Berman,et al.  Retinal damage by light in rats. , 1966, Investigative ophthalmology.

[25]  Ronald Klein,et al.  The epidemiology of progression of pure geographic atrophy: the Beaver Dam Eye Study. , 2008, American journal of ophthalmology.

[26]  T. Becker,et al.  CFH, C3 and ARMS2 Are Significant Risk Loci for Susceptibility but Not for Disease Progression of Geographic Atrophy Due to AMD , 2009, PloS one.

[27]  U. Mansmann,et al.  Concordance of disease progression in bilateral geographic atrophy due to AMD. , 2010, Investigative ophthalmology & visual science.

[28]  William J Feuer,et al.  Spectral domain optical coherence tomographic imaging of geographic atrophy. , 2008, Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye.

[29]  B. Bouma,et al.  Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography. , 2003, Optics letters.

[30]  Paul Mitchell,et al.  Ten-year incidence and progression of age-related maculopathy: the blue Mountains Eye Study. , 2007, Ophthalmology.

[31]  P. Charbel Issa,et al.  In vivo imaging of foveal sparing in geographic atrophy secondary to age-related macular degeneration. , 2009, Investigative ophthalmology & visual science.

[32]  Steffen Schmitz-Valckenberg,et al.  Fundus autofluorescence and progression of age-related macular degeneration. , 2009, Survey of ophthalmology.

[33]  J. Dreyhaupt,et al.  Fundus autofluorescence and fundus perimetry in the junctional zone of geographic atrophy in patients with age-related macular degeneration. , 2004, Investigative ophthalmology & visual science.

[34]  Andrea Hassenstein,et al.  Clinical use and research applications of Heidelberg retinal angiography and spectral‐domain optical coherence tomography – a review , 2009, Clinical & experimental ophthalmology.

[35]  W. Green,et al.  SENILE MACULAR DEGENERATION: A HISTOPATHOLOGIC STUDY* , 2005, Retina.

[36]  Thomas J. Liesegang,et al.  An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration.Hageman GS,∗ Luthert PJ, Chong NHV, Johnson LV, Anderson DH, Mullins RF. Prog Ret Eye Res 2001:20:705–732. , 2002 .

[37]  U. Schmidt-Erfurth,et al.  Human macula investigated in vivo with polarization-sensitive optical coherence tomography. , 2006, Investigative ophthalmology & visual science.

[38]  R. Krueger,et al.  Corneal and Flap Thickness Monitoring With OCT During and Following Intra LASIK , 2007 .

[39]  Sebastian Wolf,et al.  Morphologic changes in patients with geographic atrophy assessed with a novel spectral OCT-SLO combination. , 2008, Investigative ophthalmology & visual science.

[40]  Maciej Wojtkowski,et al.  Ophthalmic imaging by spectral optical coherence tomography. , 2004, American journal of ophthalmology.

[41]  Hendrik P N Scholl,et al.  Multimodal imaging including spectral domain OCT and confocal near infrared reflectance for characterization of outer retinal pathology in pseudoxanthoma elasticum. , 2009, Investigative ophthalmology & visual science.

[42]  Noemi Lois,et al.  Fundus autofluorescence in patients with age-related macular degeneration and high risk of visual loss. , 2002, American journal of ophthalmology.

[43]  J. Dreyhaupt,et al.  Modelling the Natural History of Geographic Atrophy in Patients with Age-Related Macular Degeneration , 2005, Ophthalmic epidemiology.

[44]  Steffen Schmitz-Valckenberg,et al.  Correlation of lines of increased autofluorescence in macular dystrophy and pigmented paravenous retinochoroidal atrophy by optical coherence tomography. , 2008, Archives of ophthalmology.

[45]  A Hofman,et al.  Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam Study. , 1998, Archives of ophthalmology.

[46]  R Theodore Smith,et al.  Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration. , 2006, Investigative ophthalmology & visual science.

[47]  Sonia H Yoo,et al.  Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. , 2003, Survey of ophthalmology.

[48]  Jens Dreyhaupt,et al.  Correlation between the area of increased autofluorescence surrounding geographic atrophy and disease progression in patients with AMD. , 2006, Investigative ophthalmology & visual science.

[49]  M. Killingsworth,et al.  Evolution of geographic atrophy of the retinal pigment epithelium , 1988, Eye.

[50]  R. Klein,et al.  Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. , 2003, Ophthalmology.

[51]  W. Drexler.  Ultrahigh-resolution optical coherence tomography. , 2004, Journal of biomedical optics.