Multimodal Imaging Patterns for Development of Central Atrophy Secondary to Age-Related Macular Degeneration.

Purpose To evaluate the development of central atrophy in eyes with age-related macular degeneration (AMD). Methods Six-year longitudinal multimodal retinal imaging data (MODIAMD study) from 98 eyes of 98 subjects with non-late-stage AMD in the study eye at baseline were analyzed for the presence of central atrophy at each annual follow-up visit. Development, manifestation, and further progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) by multimodal imaging data were compared with atrophy detection based on color fundus photography only. Results Seventeen study eyes with development of central cRORA within 6 years (cumulative rate: 17.4%) were identified based on multimodal imaging. In 10 (60%) of these eyes, presence of central manifest atrophy was initially not detectable by color fundus photography. In six (35%) eyes, central cRORA occurred by the spread of existing paracentral atrophy toward the fovea. Drusen-associated atrophy development was noted in eight eyes. In two eyes, atrophy development was associated with refractile deposits, while only pigmentary changes in absence of large drusen or refractile deposits were detectable before atrophy occurrence in one eye. Conclusions The earlier and more precise detection of central cRORA by multimodal imaging as compared to atrophy detection solely based on color fundus photography allows for more accurate detection and identification of different pathways for atrophy development. In accordance with previous clinical and histopathologic reports, the results confirm that different precursor lesions may independently proceed to central cRORA in AMD.

[1]  Lauren N Ayton,et al.  Optical coherence tomography-defined changes preceding the development of drusen-associated atrophy in age-related macular degeneration. , 2014, Ophthalmology.

[2]  L. Ayton,et al.  Reticular pseudodrusen: a risk factor for geographic atrophy in fellow eyes of individuals with unilateral choroidal neovascularization. , 2014, Ophthalmology.

[3]  Glenn J Jaffe,et al.  Growth of geographic atrophy in the comparison of age-related macular degeneration treatments trials. , 2015, Ophthalmology.

[4]  R. Klein,et al.  Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. , 2014, The Lancet. Global health.

[5]  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.

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

[7]  Steffen Schmitz-Valckenberg,et al.  Geographic atrophy: clinical features and potential therapeutic approaches. , 2014, Ophthalmology.

[8]  B. Yaspan,et al.  Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related macular degeneration , 2017, Science Translational Medicine.

[9]  R. Fimmers,et al.  Directional Kinetics of Geographic Atrophy Progression in Age-Related Macular Degeneration with Foveal Sparing. , 2013, Ophthalmology.

[10]  J. Monés,et al.  Drusen Ooze: A Novel Hypothesis in Geographic Atrophy. , 2017, Ophthalmology. Retina.

[11]  E. Souied,et al.  PATHOLOGIC INSIGHTS FROM INTEGRATED IMAGING OF RETICULAR PSEUDODRUSEN IN AGE-RELATED MACULAR DEGENERATION , 2011, Retina.

[12]  S. Schmitz-Valckenberg The Journey of “Geographic Atrophy” through Past, Present, and Future , 2017, Ophthalmologica.

[13]  J. Seddon,et al.  Optical Coherence Tomography Features Preceding the Onset of Advanced Age-Related Macular Degeneration , 2017, Investigative ophthalmology & visual science.

[14]  Giovanni Staurenghi,et al.  GEOGRAPHIC ATROPHY: Semantic Considerations and Literature Review , 2016, Retina.

[15]  S. Sadda,et al.  Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain optical coherence tomography: the IN•OCT consensus. , 2014, Ophthalmology.

[16]  Sina Farsiu,et al.  Optical Coherence Tomography Predictors of Risk for Progression to Non-Neovascular Atrophic Age-Related Macular Degeneration. , 2017, Ophthalmology.

[17]  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.

[18]  G. Ying,et al.  Incidence and Growth of Geographic Atrophy during 5 Years of Comparison of Age-Related Macular Degeneration Treatments Trials. , 2017, Ophthalmology.

[19]  R. Spaide OUTER RETINAL ATROPHY AFTER REGRESSION OF SUBRETINAL DRUSENOID DEPOSITS AS A NEWLY RECOGNIZED FORM OF LATE AGE-RELATED MACULAR DEGENERATION , 2013, Retina.

[20]  Cynthia A Toth,et al.  Spectral-domain optical coherence tomography characteristics of intermediate age-related macular degeneration. , 2013, Ophthalmology.

[21]  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.

[22]  F. Holz,et al.  DEVELOPMENT OF INTRARETINAL CYSTOID LESIONS IN EYES WITH INTERMEDIATE AGE-RELATED MACULAR DEGENERATION , 2016, Retina.

[23]  Usha Chakravarthy,et al.  Clinical classification of age-related macular degeneration. , 2013, Ophthalmology.

[24]  Glenn J Jaffe,et al.  Semiautomated image processing method for identification and quantification of geographic atrophy in age-related macular degeneration. , 2011, Investigative ophthalmology & visual science.

[25]  E. Souied,et al.  HYPERREFLECTIVE PYRAMIDAL STRUCTURES ON OPTICAL COHERENCE TOMOGRAPHY IN GEOGRAPHIC ATROPHY AREAS , 2014, Retina.

[26]  F. Holz,et al.  Reticular drusen in eyes with high-risk characteristics for progression to late-stage age-related macular degeneration , 2015, British Journal of Ophthalmology.

[27]  Kang Zhang,et al.  Fellow Eye Comparisons for 7-Year Outcomes in Ranibizumab-Treated AMD Subjects from ANCHOR, MARINA, and HORIZON (SEVEN-UP Study). , 2016, Ophthalmology.

[28]  Sina Farsiu,et al.  Progression of intermediate age-related macular degeneration with proliferation and inner retinal migration of hyperreflective foci. , 2013, Ophthalmology.

[29]  Christian Wojek,et al.  Automated Retinal Image Analysis for Evaluation of Focal Hyperpigmentary Changes in Intermediate Age-Related Macular Degeneration , 2016, Translational vision science & technology.

[30]  The Age-Related Eye Disease Study system for classifying age-related macular degeneration from stereoscopic color fundus photographs: the Age-Related Eye Disease Study Report Number 6. , 2001, American journal of ophthalmology.

[31]  Glenn J Jaffe,et al.  Imaging Protocols in Clinical Studies in Advanced Age-Related Macular Degeneration: Recommendations from Classification of Atrophy Consensus Meetings. , 2017, Ophthalmology.

[32]  U. Schmidt-Erfurth,et al.  Randomized Trial to Evaluate Tandospirone in Geographic Atrophy Secondary to Age-Related Macular Degeneration: The GATE Study. , 2015, American journal of ophthalmology.

[33]  Thomas Ach,et al.  Activated Retinal Pigment Epithelium, an Optical Coherence Tomography Biomarker for Progression in Age-Related Macular Degeneration , 2017, Investigative ophthalmology & visual science.

[34]  Christine Adrion,et al.  Tracking progression with spectral-domain optical coherence tomography in geographic atrophy caused by age-related macular degeneration. , 2010, Investigative ophthalmology & visual science.

[35]  Glenn J Jaffe,et al.  Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3. , 2017, Ophthalmology.

[36]  Jesse J. Jung,et al.  Associations Between Retinal Pigment Epithelium and Drusen Volume Changes During the Lifecycle of Large Drusenoid Pigment Epithelial Detachments , 2016, Investigative ophthalmology & visual science.

[37]  J D Gass,et al.  Drusen and disciform macular detachment and degeneration. , 1973, Archives of ophthalmology.

[38]  Glenn J Jaffe,et al.  Natural History of Geographic Atrophy Progression Secondary to Age-Related Macular Degeneration (Geographic Atrophy Progression Study). , 2016, Ophthalmology.

[39]  Kang Zhang,et al.  Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). , 2013, Ophthalmology.

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

[41]  Giovanni Gregori,et al.  En Face Optical Coherence Tomography Imaging for the Detection of Nascent Geographic Atrophy. , 2017, American journal of ophthalmology.

[42]  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.

[43]  Richard F Spaide,et al.  IMPROVING THE AGE-RELATED MACULAR DEGENERATION CONSTRUCT: A New Classification System. , 2017, Retina.

[44]  Sandra S Stinnett,et al.  Optical Coherence Tomography Reflective Drusen Substructures Predict Progression to Geographic Atrophy in Age-related Macular Degeneration. , 2016, Ophthalmology.

[45]  Amitha Domalpally,et al.  Methods and reproducibility of grading optimized digital color fundus photographs in the Age-Related Eye Disease Study 2 (AREDS2 Report Number 2). , 2013, Investigative ophthalmology & visual science.

[46]  L. Ayton,et al.  Fundus autofluorescence characteristics of nascent geographic atrophy in age-related macular degeneration. , 2015, Investigative ophthalmology & visual science.

[47]  F. Holz,et al.  Prevalence, Natural Course, and Prognostic Role of Refractile Drusen in Age-Related Macular Degeneration. , 2017, Investigative ophthalmology & visual science.

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

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