The "diffuse-trickling" fundus autofluorescence phenotype in geographic atrophy.

PURPOSE To further characterize a subgroup of patients exhibiting the fundus autofluorescence (FAF) "diffuse-trickling" phenotype associated with geographic atrophy (GA). METHODS In the context of the Fundus Autofluorescence in Age-Related Macular Degeneration (FAM) Study, patients with diffuse-trickling GA were examined and characterized by FAF and spectral-domain optical coherence tomography imaging. Age, sex distribution, and medical history were compared with FAM study patients (n = 288, 60.1% female) with other GA phenotypes (non-diffuse-trickling). In a subset of patients, subfoveal choroidal thickness (SCT) was analyzed. RESULTS Patients with diffuse-trickling (n = 61), compared with patients with non-diffuse-trickling GA, had a significantly younger age at first presentation (68.2 ± 11.6 vs. 75.4 ± 8.1 years, P < 0.001), a shift in the proportion of men from 55% in the age group younger than 65 to 19% in the age group older than or equal to 65, and a significantly higher rate of myocardial infarction (MI) in the age group younger than 65 (24% vs. 0%, P = 0.011); all but one patient with MI were male. Further evaluation revealed that in the age group younger than 65, 54% of patients with diffuse-trickling had been hospitalized due to cardiovascular diseases including hypertensive crisis, angina, and MI. Analysis of choroidal thickness revealed a significantly thinner SCT in diffuse-trickling compared with non-diffuse-trickling GA (135.2 ± 56.4 vs. 191.4 ± 77.8 μm, P < 0.001). CONCLUSIONS The results indicate an association of diffuse-trickling GA with systemic cardiovascular disorders in the younger study population. Together with the ocular morphologic characteristics including a lobular appearance and a thin choroid, a vascular insufficiency at the level of the choroid may play a pathogenetic role in this distinct GA phenotype. (ClinicalTrials.gov number, NCT00393692.).

[1]  S. Tsang,et al.  Reticular pseudodrusen in early age-related macular degeneration are associated with choroidal thinning. , 2013, Investigative ophthalmology & visual science.

[2]  P. Heiduschka,et al.  Localized reticular pseudodrusen and their topographic relation to choroidal watershed zones and changes in choroidal volumes. , 2013, Investigative ophthalmology & visual science.

[3]  G. Holder,et al.  Phenotypic findings in C1QTNF5 retinopathy (late‐onset retinal degeneration) , 2013, Acta ophthalmologica.

[4]  E. Souied,et al.  Choroidal changes associated with reticular pseudodrusen. , 2012, Investigative ophthalmology & visual science.

[5]  K. Nakashima,et al.  [The Rotterdam study]. , 2011, Nihon rinsho. Japanese journal of clinical medicine.

[6]  U. Mansmann,et al.  Progression of age-related geographic atrophy: role of the fellow eye. , 2011, Investigative ophthalmology & visual science.

[7]  R. T. Smith,et al.  Image registration and multimodal imaging of reticular pseudodrusen. , 2011, Investigative ophthalmology & visual science.

[8]  Steffen Schmitz-Valckenberg,et al.  Fundus autofluorescence and spectral-domain optical coherence tomography characteristics in a rapidly progressing form of geographic atrophy. , 2011, Investigative ophthalmology & visual science.

[9]  P. Mitchell,et al.  Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis , 2010, BMC ophthalmology.

[10]  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.

[11]  Steffen Schmitz-Valckenberg,et al.  Combined confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography imaging of reticular drusen associated with age-related macular degeneration. , 2010, Ophthalmology.

[12]  C. Curcio,et al.  Reticular pseudodrusen are subretinal drusenoid deposits. , 2010, Ophthalmology.

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

[14]  Takayuki Baba,et al.  Relationship between RPE and choriocapillaris in age-related macular degeneration. , 2009, Investigative ophthalmology & visual science.

[15]  Richard F Spaide,et al.  Age-related choroidal atrophy. , 2009, American journal of ophthalmology.

[16]  R. Spaide,et al.  A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. , 2009, American journal of ophthalmology.

[17]  B. J. Klevering,et al.  Central areolar choroidal dystrophy. , 2009, Ophthalmology.

[18]  C. Hamel,et al.  Extensive macular atrophy with pseudodrusen-like appearance: a new clinical entity. , 2009, American journal of ophthalmology.

[19]  A. Wright,et al.  Late-onset retinal macular degeneration: clinical insights into an inherited retinal degeneration , 2008, Postgraduate Medical Journal.

[20]  B. Feigl Age-related maculopathy – Linking aetiology and pathophysiological changes to the ischaemia hypothesis , 2008, Progress in Retinal and Eye Research.

[21]  Thomas Theelen,et al.  Fundus autofluorescence imaging of retinal dystrophies , 2008, Vision Research.

[22]  C. Curcio,et al.  Sub-retinal drusenoid deposits in human retina: organization and composition. , 2008, Experimental eye research.

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

[24]  A. Fletcher,et al.  Cardiovascular disease and hypertension are strong risk factors for choroidal neovascularization. , 2008, Ophthalmology.

[25]  R. Klein,et al.  The epidemiology of retinal reticular drusen. , 2008, American journal of ophthalmology.

[26]  R. Klein,et al.  Age-related macular degeneration is associated with incident myocardial infarction among elderly Americans. , 2007, Ophthalmology.

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

[28]  R. Klein,et al.  Age-Related Macular Degeneration and Risk for Stroke , 2006, Annals of Internal Medicine.

[29]  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.

[30]  Giovanni Staurenghi,et al.  Classification of fundus autofluorescence patterns in early age-related macular disease. , 2005, Investigative ophthalmology & visual science.

[31]  P. Sieving,et al.  Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation. , 2005, Investigative ophthalmology & visual science.

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

[33]  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.

[34]  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.

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

[36]  P. Jong Prevalence of age-related macular degeneration in the United States. , 2004 .

[37]  Daniel W. Jones,et al.  Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. , 2003, Hypertension.

[38]  A. Hofman,et al.  Blood pressure, atherosclerosis, and the incidence of age-related maculopathy : The Rotterdam Study , 2003 .

[39]  R. Klein,et al.  The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam eye study. , 2003, Ophthalmology.

[40]  Sebastian Wolf,et al.  Changes in fundus autofluorescence in patients with age-related maculopathy. Correlation to visual function: a prospective study , 2003, Graefe's Archive for Clinical and Experimental Ophthalmology.

[41]  A. Hofman,et al.  The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years in the Rotterdam study. , 2003, Archives of ophthalmology.

[42]  R. Klein,et al.  Ten-year incidence and progression of age-related maculopathy: The Beaver Dam eye study. , 2002, Ophthalmology.

[43]  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.

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

[45]  M. C. Leske,et al.  Hypertension, cardiovascular disease, and age-related macular degeneration. Age-Related Macular Degeneration Risk Factors Study Group. , 2000, Archives of ophthalmology.

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

[47]  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.

[48]  F W Fitzke,et al.  In vivo fundus autofluorescence in macular dystrophies. , 1997, Archives of ophthalmology.

[49]  A. Hofman,et al.  Age-related macular degeneration and smoking. The Rotterdam Study. , 1996 .

[50]  J. J. Wang,et al.  Prevalence of age-related maculopathy in Australia. The Blue Mountains Eye Study. , 1995, Ophthalmology.

[51]  M L Bots,et al.  Age-related macular degeneration is associated with atherosclerosis. The Rotterdam Study. , 1995, American journal of epidemiology.

[52]  A C Bird,et al.  Bilateral macular drusen in age-related macular degeneration. Prognosis and risk factors. , 1994, Ophthalmology.

[53]  W R Green,et al.  Age-related Macular Degeneration Histopathologic Studies: The 1992 Lorenz E. Zimmerman Lecture , 1993, Ophthalmology.

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

[55]  P. Maguire,et al.  Geographic atrophy of the retinal pigment epithelium. , 1986, American journal of ophthalmology.

[56]  S S Hayreh,et al.  Fundus lesions in malignant hypertension. VI. Hypertensive choroidopathy. , 1986, Ophthalmology.

[57]  M. Tso,et al.  Fundus lesions in malignant hypertension. I. A pathologic study of experimental hypertensive choroidopathy. , 1985, Archives of ophthalmology.

[58]  B S Fine,et al.  A histologic study of regional choroidal dystrophy. , 1977, American journal of ophthalmology.

[59]  S. Sarks,et al.  Ageing and degeneration in the macular region: a clinico-pathological study. , 1976, The British journal of ophthalmology.

[60]  M. Tso,et al.  The architecture of the choriocapillaris at the posterior pole. , 1976, American journal of ophthalmology.

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

[62]  Maria Adler,et al.  Stereoscopic Atlas Of Macular Diseases , 2016 .

[63]  R. Klein,et al.  Early age-related maculopathy in the cardiovascular health study. , 2003, Ophthalmology.

[64]  J. Seddon,et al.  Do age-related macular degeneration and cardiovascular disease share common antecedents? , 1999, Ophthalmic epidemiology.

[65]  R. Klein,et al.  The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. , 1997, Ophthalmology.

[66]  M. Killingsworth,et al.  RETICULAR PSEUDODRUSEN: A Risk Factor in Age-Related Maculopathy , 1995, Retina.