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Solly Elmann, Matthew S J Katz, Natsumi Takahashi, Bert M Glaser; Low Vitreous Protein Levels are Associated with Reticular Pseudodrusen. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5776.
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© ARVO (1962-2015); The Authors (2016-present)
Neovascular age-related macular degeneration (nAMD) is a disease encompassing variable phenotypes. Reticular pseudodrusen (RPD) comprise an anatomic variant associated with the development of geographic atrophy and poor visual outcomes. Vitreous proteomics is evolving as a method to gain insight into the disease process and characterization of AMD. As a first step in studying the vitreous proteome associated with RPD, we examined the correlation between vitreous total protein levels and the presence of RPD.
Sequential vitreous aspirates (50-120 μL) were obtained from 568 subjects immediately prior to intravitreal injection for the treatment of nAMD between January 1, 2007 and August 1, 2015 in an IRB approved study. All vitreous samples were investigated utilizing RPPM (Reverse Phase Protein Microarray) technology. Total protein levels were calculated using the Pierce 660 nm Protein Assay (Thermo Scientific, NanoDrop 2000). Fluorescein angiography, indocyanide green angiography, SD-OCT, fundus autofluorescence and infrared imaging of all patients were reviewed preceding treatment.
Of the 568 samples obtained, a consistently low total protein level (defined as 2 or more samples lower than 0.06 mg/mL total protein concentration) was found in 26 eyes of 22 subjects. The average total vitreous protein was 0.81 mg/mL. Of these, 13 eyes of 11 subjects (50%) demonstrated RPD as defined by fluorescein angiography, fundus autofluorescence, infrared imaging, and SD-OCT. Conversely 19 eyes of 16 patients were identified with total protein above 4.0 mg/mL for comparison. Of these, 1 eye of 1 subject had RPD (5%).
RPD has a reported incidence of 20-24% in nAMD patients, In the current study, eyes with a low total vitreous protein concentrations had a 50% incidence of RPD. RPD has been associated with poorer prognosis, a higher incidence of geographic atrophy and progression to severe nAMD. Our findings suggest a possible pathophysiological correlate between RPD and low levels of vitreous total protein. Further studies to determine specific biomarker levels associated with low vitreous total protein and their changes over time with treatment and progression are currently underway. Such investigations may help in further characterizing and understanding RPD and the progression of AMD.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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