Chandrakumar Balaratnasingam1, Svetlana Cherepanoff2, Rosa Dolz-Marco3, Murray Killingsworth4, Fred K Chen5, Randev Mendis6, Sarah Mrejen7, Lay Khoon Too8, Orly Gal-Or9, Christine A Curcio10, K Bailey Freund11, Lawrence A Yannuzzi12. 1. LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; Vitreous Retina Macula Consultants of New York, New York, New York; Department of Ophthalmology, New York University School of Medicine, New York, New York; Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Australia; Lions Eye Institute, Nedlands, Western Australia, Australia; Department of Ophthalmology, Sir Charles Gairdner Hospital, Western Australia, Australia. 2. St. Vincent's Hospital, Sydney, N.S.W., Australia. 3. LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; Vitreous Retina Macula Consultants of New York, New York, New York. 4. Discipline of Pathology, School of Medicine, Western Sydney University, Sydney, Australia; Faculty of Medicine, South Western Sydney Clinical School, University of New South Wales, Sydney, Australia; Ingham Institute, Liverpool, N.S.W., Australia. 5. Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Australia; Lions Eye Institute, Nedlands, Western Australia, Australia; Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia. 6. Canberra Retina Clinic, Australian Capital Territory, Australia. 7. Department of Ophthalmology, University Paris Est, Intercity Hospital, Creteil, France. 8. The University of Sydney, N.S.W., Australia. 9. LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; Vitreous Retina Macula Consultants of New York, New York, New York; Rabin Medical Center, Petach-Tikva, Israel. 10. Department of Ophthalmology, University of Alabama School at Birmingham, Birmingham, Alabama. 11. LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; Vitreous Retina Macula Consultants of New York, New York, New York; Department of Ophthalmology, New York University School of Medicine, New York, New York. 12. LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; Vitreous Retina Macula Consultants of New York, New York, New York. Electronic address: layannuzzi@gmail.com.
Abstract
PURPOSE: To define the range and life cycles of cuticular drusen phenotypes using multimodal imaging and to review the histologic characteristics of cuticular drusen. DESIGN: Retrospective, observational cohort study and experimental laboratory study. PARTICIPANTS: Two hundred forty eyes of 120 clinic patients with a cuticular drusen phenotype and 4 human donor eyes with cuticular drusen (n = 2), soft drusen (n = 1), and hard drusen (n = 1). METHODS: We performed a retrospective review of clinical and multimodal imaging data of patients with a cuticular drusen phenotype. Patients had undergone imaging with various combinations of color photography, fluorescein angiography, indocyanine green angiography, near-infrared reflectance, fundus autofluorescence, high-resolution OCT, and ultrawide-field imaging. Human donor eyes underwent processing for high-resolution light and electron microscopy. MAIN OUTCOME MEASURES: Appearance of cuticular drusen in multimodal imaging and the topography of a cuticular drusen distribution; age-dependent variations in cuticular drusen phenotypes, including the occurrence of retinal pigment epithelium (RPE) abnormalities, choroidal neovascularization, acquired vitelliform lesions (AVLs), and geographic atrophy (GA); and ultrastructural and staining characteristics of druse subtypes. RESULTS: The mean age of patients at the first visit was 57.9±13.4 years. Drusen and RPE changes were seen in the peripheral retina, anterior to the vortex veins, in 21.8% of eyes. Of eyes with more than 5 years of follow-up, cuticular drusen disappeared from view in 58.3% of eyes, drusen coalescence was seen in 70.8% of eyes, and new RPE pigmentary changes developed in 56.2% of eyes. Retinal pigment epithelium abnormalities, AVLs, neovascularization, and GA occurred at a frequency of 47.5%, 24.2%, 12.5%, and 25%, respectively, and were significantly more common in patients older than 60 years of age (all P < 0.015). Occurrence of GA and neovascularization were important determinants of final visual acuity in eyes with the cuticular drusen phenotype (both P < 0.015). Small cuticular drusen typically demonstrated a homogenous ultrastructural appearance similar to hard drusen, whereas fragmentation of the central and basal contents was seen frequently in larger cuticular drusen. CONCLUSIONS: Although the ultrastructural characteristics of cuticular drusen appear more similar to those of hard drusen, their lifecycle and macular complications are more comparable with those of soft drusen. Cuticular drusen phenotype may confer a unique risk for the development of GA and neovascularization.
PURPOSE: To define the range and life cycles of cuticular drusen phenotypes using multimodal imaging and to review the histologic characteristics of cuticular drusen. DESIGN: Retrospective, observational cohort study and experimental laboratory study. PARTICIPANTS: Two hundred forty eyes of 120 clinic patients with a cuticular drusen phenotype and 4 humandonor eyes with cuticular drusen (n = 2), soft drusen (n = 1), and hard drusen (n = 1). METHODS: We performed a retrospective review of clinical and multimodal imaging data of patients with a cuticular drusen phenotype. Patients had undergone imaging with various combinations of color photography, fluorescein angiography, indocyanine green angiography, near-infrared reflectance, fundus autofluorescence, high-resolution OCT, and ultrawide-field imaging. Humandonor eyes underwent processing for high-resolution light and electron microscopy. MAIN OUTCOME MEASURES: Appearance of cuticular drusen in multimodal imaging and the topography of a cuticular drusen distribution; age-dependent variations in cuticular drusen phenotypes, including the occurrence of retinal pigment epithelium (RPE) abnormalities, choroidal neovascularization, acquired vitelliform lesions (AVLs), and geographic atrophy (GA); and ultrastructural and staining characteristics of druse subtypes. RESULTS: The mean age of patients at the first visit was 57.9±13.4 years. Drusen and RPE changes were seen in the peripheral retina, anterior to the vortex veins, in 21.8% of eyes. Of eyes with more than 5 years of follow-up, cuticular drusen disappeared from view in 58.3% of eyes, drusen coalescence was seen in 70.8% of eyes, and new RPE pigmentary changes developed in 56.2% of eyes. Retinal pigment epithelium abnormalities, AVLs, neovascularization, and GA occurred at a frequency of 47.5%, 24.2%, 12.5%, and 25%, respectively, and were significantly more common in patients older than 60 years of age (all P < 0.015). Occurrence of GA and neovascularization were important determinants of final visual acuity in eyes with the cuticular drusen phenotype (both P < 0.015). Small cuticular drusen typically demonstrated a homogenous ultrastructural appearance similar to hard drusen, whereas fragmentation of the central and basal contents was seen frequently in larger cuticular drusen. CONCLUSIONS: Although the ultrastructural characteristics of cuticular drusen appear more similar to those of hard drusen, their lifecycle and macular complications are more comparable with those of soft drusen. Cuticular drusen phenotype may confer a unique risk for the development of GA and neovascularization.
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