Rosa Dolz-Marco1, Jay P Glover2, Orly Gal-Or3, Katie M Litts4, Jeffrey D Messinger2, Yuhua Zhang2, Mariano Cozzi5, Marco Pellegrini5, K Bailey Freund6, Giovanni Staurenghi5, Christine A Curcio7. 1. Vitreous Retina Macula Consultants of New York, New York, New York; LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; FISABIO Ophthalmology Medicine, Valencia, Spain. 2. Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama. 3. Vitreous Retina Macula Consultants of New York, New York, New York; LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; Department of Ophthalmology, Rabin Medical Center, Petach-Tikva, Israel. 4. Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama; Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin. 5. Eye Clinic, Department of Biomedical and Clinical Science "Luigi Sacco," University of Milan, Milan, Italy. 6. Vitreous Retina Macula Consultants of New York, New York, New York; LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University College of Physicians and Surgeons, New York, New York; Department of Ophthalmology, New York University School of Medicine, New York, New York. 7. Vitreous Retina Macula Consultants of New York, New York, New York. Electronic address: curcio@uab.edu.
Abstract
PURPOSE: To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases. DESIGN: Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis. PARTICIPANTS: Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4). METHODS: Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging. MAIN OUTCOME MEASURES: Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging. RESULTS: Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9±37.8 μm and 65.4±27.9 μm, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns. CONCLUSIONS: Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging.
PURPOSE: To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases. DESIGN: Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis. PARTICIPANTS: Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4). METHODS:Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging. MAIN OUTCOME MEASURES: Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging. RESULTS: Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9±37.8 μm and 65.4±27.9 μm, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns. CONCLUSIONS: Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging.
Authors: Christine A Curcio; Jeffrey D Messinger; Kenneth R Sloan; Arnab Mitra; Gerald McGwin; Richard F Spaide Journal: Invest Ophthalmol Vis Sci Date: 2011-06-06 Impact factor: 4.799
Authors: Alan D Marmorstein; Lihua Y Marmorstein; Hirokazu Sakaguchi; Joe G Hollyfield Journal: Invest Ophthalmol Vis Sci Date: 2002-07 Impact factor: 4.799
Authors: Elliott H Sohn; Aditi Khanna; Budd A Tucker; Michael D Abràmoff; Edwin M Stone; Robert F Mullins Journal: Invest Ophthalmol Vis Sci Date: 2014-03-06 Impact factor: 4.799
Authors: Giuseppe Querques; Eliana Costanzo; Alexandra Miere; Vittorio Capuano; Eric H Souied Journal: Invest Ophthalmol Vis Sci Date: 2016-05-01 Impact factor: 4.799
Authors: Lynn W Sun; Ryan D Johnson; Vesper Williams; Phyllis Summerfelt; Alfredo Dubra; David V Weinberg; Kimberly E Stepien; Gerald A Fishman; Joseph Carroll Journal: PLoS One Date: 2016-12-09 Impact factor: 3.240
Authors: Benjamin S Echols; Mark E Clark; Thomas A Swain; Ling Chen; Deepayan Kar; Yuhua Zhang; Kenneth R Sloan; Gerald McGwin; Ramya Singireddy; Christian Mays; David Kilpatrick; Jason N Crosson; Cynthia Owsley; Christine A Curcio Journal: Ophthalmol Retina Date: 2020-05-07
Authors: Miaoling Li; Rosa Dolz-Marco; Carrie Huisingh; Jeffrey D Messinger; Richard M Feist; Daniela Ferrara; K Bailey Freund; Christine A Curcio Journal: Retina Date: 2019-04 Impact factor: 4.256