title: An Ocular Protein Triad Can Classify Four Complex Retinal Diseases.
abstract: Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test. Unsupervised clustering of ocular proteins revealed a classification strikingly similar to the clinical phenotypes of each disease group studied. We developed and independently validated a parsimonious model based merely on three proteins; interleukin (IL)-10, IL-21, and angiotensin converting enzyme (ACE) that could correctly classify patients with an overall accuracy, sensitivity and specificity of respectively, 86.7%, 79.4% and 92.5%. Here, we provide proof-of-concept for molecular profiling as a diagnostic aid for ophthalmologists in the care for patients with retinal conditions.
authors.affiliation: Laboratory of Translational Immunology, department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J J W
authors.initials: JJ
authors.lastname: Kuiper
authors.affiliation: Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Beretta
authors.affiliation: Laboratory of Translational Immunology, department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Nierkens
authors.affiliation: Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van Leeuwen
authors.affiliation: Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: N H
authors.initials: NH
authors.lastname: Ten Dam-van Loon
authors.affiliation: Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Ossewaarde-van Norel
authors.affiliation: Department of Ophthalmology, Deventer Hospital, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Bartels
authors.affiliation: Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.|Deparment of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J D F
authors.initials: JD
authors.lastname: de Groot-Mijnes
authors.affiliation: Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Schellekens
authors.affiliation: Laboratory of Translational Immunology, department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: de Boer
authors.affiliation: Laboratory of Translational Immunology, department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Clinical Immunology and Rheumatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: T R D J
authors.initials: TR
authors.lastname: Radstake
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001082:Aqueous Humor / Q000378:metabolism; D015415:Biomarkers; D000066491:Clinical Decision-Making; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D012164:Retinal Diseases / Q000175:diagnosis* / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D005136:Eye Proteins; D020543:Proteome