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.

Combined cellular and soluble mediator analysis for improved diagnosis of vitreoretinal lymphoma

“…In a recent report, Kuiper et al. () also found evidence for IL‐10 and MCP‐1 to distinguish (P)VRL from a.o. non‐infectious uveitis.…”

Personalized Proteomics for Precision Health: Identifying Biomarkers of Vitreoretinal Disease

“… 15 More importantly, this could redirect the diagnosis and treatment of a patient who had been previously diagnosed with idiopathic posterior uveitis. 15 In a similar study, Kuiper et al 85 used a multiplex ELISA (25 proteins) to analyze 175 aqueous humor samples from four retinal diseases (rhegmatogenous RD, AMD, primary vitreoretinal lymphoma, and idiopathic noninfectious uveitis). 85 Three proteins (IL-10, IL-21, and ACE) were further analyzed, using a parsimonious model that could distinguish the four diseases from each other, with 86.7% accuracy.…”

“… 15 In a similar study, Kuiper et al 85 used a multiplex ELISA (25 proteins) to analyze 175 aqueous humor samples from four retinal diseases (rhegmatogenous RD, AMD, primary vitreoretinal lymphoma, and idiopathic noninfectious uveitis). 85 Three proteins (IL-10, IL-21, and ACE) were further analyzed, using a parsimonious model that could distinguish the four diseases from each other, with 86.7% accuracy. 85 This study highlights the potential for proteomic analysis to guide the definitive diagnosis of vitreoretinal diseases.…”

“… 85 Three proteins (IL-10, IL-21, and ACE) were further analyzed, using a parsimonious model that could distinguish the four diseases from each other, with 86.7% accuracy. 85 This study highlights the potential for proteomic analysis to guide the definitive diagnosis of vitreoretinal diseases.…”

Emerging diagnostic tests for vitreoretinal lymphoma: a review

“…). A different approach has been developed to add proteins to the screening process: a group of investigators based at the University Medical Center Utrecht identified an ‘ocular protein triad’ of IL‐10, IL‐21 and angiotensin‐converting enzyme in aqueous through an unbiased cluster analysis of a 27‐protein multiplex immunoassay. Aqueous samples came from a group of 128 patients with diagnoses that included vitreoretinal lymphoma, uveitis, rhegmatogenous retinal detachment and neovascular age‐related macular degeneration.…”