A Pilot Quantitative Study of Topographic Correlation between Reticular Pseudodrusen and the Choroidal Vasculature Using En Face Optical Coherence Tomography
Purpose To analyze the topographic correlation between reticular pseudodrusen (RPD) visualized on infrared reflectance (IR) and choroidal vasculature using en-face volumetric spectral-domain optical coherence tomography (SD-OCT). Methods A masked observer marked individual RPD on IR images using ImageJ (NIH, Bethesda, MD). Using the macular volume scan (Cirrus, Carl Zeiss Meditec Inc, Dublin, CA), the RPE slab function was used to generate a C-scan of the most superficial choroidal vasculature. An independent masked grader created a topographic binary map of the choroidal vasculature by thresholding the en-face image, which was overlaid onto the IR map of RPD. For each IR image, ImageJ was used to generate a random set of dots as “control lesions”. Results 17 eyes of 11 patients (78±13.7 years) with RPD were analyzed. The average number of RPD lesions identified on IR images was 414±71.5, of which 49.6±4.3% were located overlying the choroidal vasculature, compared to 45.4±4.0% in controls (p = 0.014). 50.4±4.3% of lesions overlay the choroidal stroma, of which 76.5±3.1% were ≤3 pixels from the choroidal vessels. The percentage of RPD lesions located within ≤3 pixels from the choroidal vasculature was significantly greater than the percentage located ≥7 pixels away. (p<0.0001). Compared to controls (71.6±3.8%), RPD were more likely to be located ≤3 pixels away from choroidal vessels (p = 0.014). In contrast, control lesions were more likely to be ≥7 pixels away from choroidal vessels than RPD (9.1±1.9% vs. 4.8±1.2%, respectively, p = 0.002). Conclusions Our analysis shows that RPD lesions follow the underlying choroidal vasculature. Approximately half the RPD directly overlay the choroidal vessels and the majority of the remaining lesions were ≤3 pixels (≤30microns) from the vessel edge, supporting the hypothesis that RPD maybe related to pathologic changes at the choroidal level.
Cohen SY, Dubois L, Tadayoni R, Delahaye-Mazza C, Debibie C, et al. (2007) Prevalence of reticular pseudodrusen in age-related macular degeneration with newly diagnosed choroidal neovascularisation. The British journal of ophthalmology 91: 354–359. doi: 10.1136/bjo.2006.101022
[3]
Spaide RF, Curcio CA (2010) Drusen characterization with multimodal imaging. Retina 30: 1441–1454. doi: 10.1097/iae.0b013e3181ee5ce8
[4]
Zweifel SA, Spaide RF, Curcio CA, Malek G, Imamura Y (2010) Reticular pseudodrusen are subretinal drusenoid deposits. Ophthalmology 117: : 303–312 e301.
[5]
Smith RT, Sohrab MA, Busuioc M, Barile G (2009) Reticular macular disease. American journal of ophthalmology 148: : 733–743 e732.
[6]
Zweifel SA, Imamura Y, Spaide TC, Fujiwara T, Spaide RF (2010) Prevalence and significance of subretinal drusenoid deposits (reticular pseudodrusen) in age-related macular degeneration. Ophthalmology 117: 1775–1781. doi: 10.1016/j.ophtha.2010.01.027
[7]
Arnold JJ, Quaranta M, Soubrane G, Sarks SH, Coscas G (1997) Indocyanine green angiography of drusen. Am J Ophthalmol 124: 344–356. doi: 10.1007/978-94-011-5137-5_50
[8]
Sarks J, Arnold J, Ho IV, Sarks S, Killingsworth M (2011) Evolution of reticular pseudodrusen. The British journal of ophthalmology 95: 979–985. doi: 10.1136/bjo.2010.194977
[9]
Klein R, Meuer SM, Knudtson MD, Iyengar SK, Klein BE (2008) The epidemiology of retinal reticular drusen. American journal of ophthalmology 145: 317–326. doi: 10.1016/j.ajo.2007.09.008
[10]
Arnold JJ, Sarks SH, Killingsworth MC, Sarks JP (1995) Reticular pseudodrusen. A risk factor in age-related maculopathy. Retina 15: 183–191. doi: 10.1097/00006982-199515030-00001
[11]
Smith RT, Merriam JE, Sohrab MA, Pumariega NM, Barile G, et al. (2011) Complement factor H 402H variant and reticular macular disease. Archives of ophthalmology 129: 1061–1066. doi: 10.1001/archophthalmol.2011.212
[12]
Pumariega NM, Smith RT, Sohrab MA, Letien V, Souied EH (2011) A prospective study of reticular macular disease. Ophthalmology 118: 1619–1625. doi: 10.1016/j.ophtha.2011.01.029
[13]
Leng T, Rosenfeld PJ, Gregori G, Puliafito CA, Punjabi OS (2009) Spectral domain optical coherence tomography characteristics of cuticular drusen. Retina 29: 988–993. doi: 10.1097/iae.0b013e3181ae7113
[14]
Schmitz-Valckenberg S, Alten F, Steinberg JS, Jaffe GJ, Fleckenstein M, et al. (2011) Reticular drusen associated with geographic atrophy in age-related macular degeneration. Investigative ophthalmology & visual science 52: 5009–5015. doi: 10.1167/iovs.11-7235
[15]
Sohrab M, Fawzi AA (2013) Review of En-Face Choroidal Imaging Using Spectral Domain OCT. Medical Hypothesis, Discovery & Innovation Ophthalmology Journal 2(3): , 69–73.
[16]
Sohrab M, Wu K, Fawzi AA (2012) A pilot study of morphometric analysis of choroidal vasculature in vivo, using en face optical coherence tomography. PloS one 7: e48631. doi: 10.1371/journal.pone.0048631
[17]
McLeod DS, Grebe R, Bhutto I, Merges C, Baba T, et al. (2009) Relationship between RPE and Choriocapillaris in Age-Related Macular Degeneration. Investigative ophthalmology & visual science 50: 4982–4991. doi: 10.1167/iovs.09-3639
[18]
Sohrab MA, Smith RT, Salehi-Had H, Sadda SR, Fawzi AA (2011) Image registration and multimodal imaging of reticular pseudodrusen. Investigative ophthalmology & visual science 52: 5743–5748. doi: 10.1167/iovs.10-6942
[19]
Querques G, Querques L, Forte R, Massamba N, Coscas F, et al. (2012) Choroidal changes associated with reticular pseudodrusen. Investigative ophthalmology & visual science 53: 1258–1263. doi: 10.1167/iovs.11-8907
[20]
Rudolf M, Malek G, Messinger JD, Clark ME, Wang L, et al. (2008) Sub-retinal drusenoid deposits in human retina: organization and composition. Exp Eye Res 87: 402–408. doi: 10.1016/j.exer.2008.07.010
[21]
Querques G, Querques L, Martinelli D, Massamba N, Coscas G, et al. (2011) Pathologic insights from integrated imaging of reticular pseudodrusen in age-related macular degeneration. Retina 31: 518–526. doi: 10.1097/iae.0b013e3181f04974
[22]
Lengyel I, Tufail A, Hosaini HA, Luthert P, Bird AC, et al. (2004) Association of drusen deposition with choroidal intercapillary pillars in the aging human eye. Investigative ophthalmology & visual science 45: 2886–2892. doi: 10.1167/iovs.03-1083
[23]
Yasuno Y, Miura M, Kawana K, Makita S, Sato M, et al. (2009) Visualization of sub-retinal pigment epithelium morphologies of exudative macular diseases by high-penetration optical coherence tomography. Investigative ophthalmology & visual science 50: 405–413. doi: 10.1167/iovs.08-2272
[24]
Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nature methods 9: 671–675. doi: 10.1038/nmeth.2089
[25]
Curcio CA, Messinger JD, Sloan KR, McGwin G, Medeiros NE, et al. (2013) Subretinal drusenoid deposits in non-neovascular age-related macular degeneration: morphology, prevalence, topography, and biogenesis model. Retina 33: 265–276. doi: 10.1097/iae.0b013e31827e25e0
[26]
Alten F, Clemens CR, Heiduschka P, Eter N (2013) Localized reticular pseudodrusen and their topographic relation to choroidal watershed zones and changes in choroidal volumes. Investigative Ophthalmology & Visual Science.
[27]
Ueda-Arakawa N, Ooto S, Nakata I, Yamashiro K, Tsujikawa A, et al. (2013) Prevalence and Genomic Association of Reticular Pseudodrusen in Age-Related Macular Degeneration. American journal of ophthalmology 155: 260–269.e262. doi: 10.1016/j.ajo.2012.08.011
[28]
Puche N, Blanco-Garavito R, Richard F, Leveziel N, Zerbib J, et al. (2013) Genetic and environmental factors associated with reticular pseudodrusen in age-related macular degeneration. Retina 33: 998–1004. doi: 10.1097/iae.0b013e31827b6483
[29]
Gehrs KM, Jackson JR, Brown EN, Allikmets R, Hageman GS (2010) Complement, age-related macular degeneration and a vision of the future. Archives of ophthalmology 128: 349–358. doi: 10.1001/archophthalmol.2010.18
[30]
Anderson DH, Radeke MJ, Gallo NB, Chapin EA, Johnson PT, et al. (2010) The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Progress in retinal and eye research 29: 95–112. doi: 10.1016/j.preteyeres.2009.11.003
[31]
Kortvely E, Hauck SM, Duetsch G, Gloeckner CJ, Kremmer E, et al. (2010) ARMS2 is a constituent of the extracellular matrix providing a link between familial and sporadic age-related macular degenerations. Investigative ophthalmology & visual science 51: 79–88. doi: 10.1167/iovs.09-3850
[32]
Sarks SH, Arnold JJ, Killingsworth MC, Sarks JP (1999) Early drusen formation in the normal and aging eye and their relation to age related maculopathy: a clinicopathological study. Br J Ophthalmol 83: 358–368. doi: 10.1136/bjo.83.3.358
[33]
Querques G, Massamba N, Srour M, Boulanger E, Georges A, et al.. (2013) Impact of Reticular Pseudodrusen on Macular Function. Retina.
[34]
Friedman E, Smith TR, Kuwabara T (1963) Senile choroidal vascular patterns and drusen. Arch Ophthalmol 69: 220–230. doi: 10.1001/archopht.1963.00960040226014
[35]
Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, et al. (2001) 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. Progress in retinal and eye research 20: 705–732. doi: 10.1016/s1350-9462(01)00010-6
[36]
Hageman GS, Mullins RF (1999) Molecular composition of drusen as related to substructural phenotype. Molecular vision 5: 28.
[37]
Mullins RF, Russell SR, Anderson DH, Hageman GS (2000) Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J 14: 835–846.
[38]
Mullins RF, Johnson MN, Faidley EA, Skeie JM, Huang J (2011) Choriocapillaris vascular dropout related to density of drusen in human eyes with early age-related macular degeneration. Invest Ophthalmol Vis Sci 52: 1606–1612. doi: 10.1167/iovs.10-6476
[39]
Zweifel SA, Spaide RF, Yannuzzi LA (2011) Acquired vitelliform detachment in patients with subretinal drusenoid deposits (reticular pseudodrusen). Retina 31: 229–234. doi: 10.1097/iae.0b013e3181f049bd
[40]
Schwartz DM, Fingler J, Kim DY, Zawadzki RJ, Morse LS, et al.. (2013) Phase-Variance Optical Coherence Tomography: A New Technique for Noninvasive Angiography. Ophthalmology.
[41]
Jaillon F, Makita S, Min EJ, Lee BH, Yasuno Y (2011) Enhanced imaging of choroidal vasculature by high-penetration and dual-velocity optical coherence angiography. Biomed Opt Express 2: 1147–1158. doi: 10.1364/boe.2.001147
