Refine
Document Type
- Article (2)
Language
- English (2) (remove)
Has Fulltext
- yes (2)
Is part of the Bibliography
- no (2)
Keywords
- ADA (1)
- Age-related macular degeneration (1)
- Biomarker (1)
- Diabetic retinopathy (1)
- MicroRNAs (1)
- Retinal vein occlusion (1)
- VEGF inhibitors (1)
- anti-drug antibodies (1)
- brolucizumab (1)
- intraocular inflammation (1)
- intravitreal (1)
- occlusive vasculitis (1)
- ranibizumab (1)
- retinal vasculitis (1)
Institute
Publisher
- S. Karger AG (1)
- Wiley (1)
Introduction: Vessel-associated retinal diseases are a major cause of blindness and severe visual impairment. The identification of appropriate biomarkers is of great importance to better anticipate disease progression and establish more targeted treatment options. MicroRNAs (miRNAs) are short, single-stranded, noncoding ribonucleic acids that are involved in the posttranscriptional regulation of gene expression through hybridization with messenger RNA. The expression of certain miRNAs can be different in patients with pathological processes and can be used for the detection and differentiation of various diseases. In this study, we investigate to what extent previously in vitro identified miRNAs are present as cell-free circulating miRNAs in the serum and vitreous of human patients with and without vessel-associated retinal diseases. Methods: Relative quantification by quantitative real-time polymerase chain reaction was used to analyze miRNA expression in patients with vessel-associated retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion compared with control patients. Results: In serum samples, miR-29a-3p and miR-192-5p showed increased expression in patients with neovascular AMD relative to control patients. Similarly, miR-335-5p, miR-192-5p, and miR-194-5p showed increased expression in serum from patients with proliferative DR. In vitreous samples, miR-100-5p was decreased in patients with proliferative DR. Differentially expressed miRNAs showed good diagnostic accuracy in receiver operating characteristic (ROC) and area under the ROC curve analysis. Conclusion: The miRNAs investigated in this study may have the potential to serve as biomarkers for vessel-associated retinal diseases. Combining multiple miRNAs may enhance the predictive power of the analysis.
Purpose
Postapproval reports of intraocular inflammation (IOI) and occlusive retinal vasculitis following intravitreal brolucizumab are accumulating. A role of anti-drug antibodies (ADAs) to brolucizumab is under current scientific discussion. The purpose of the present study was to measure brolucizumab ADAs in a cross-sectional ophthalmic patient population and to compare the occurrence of brolucizumab ADAs with that of ranibizumab ADAs.
Methods
One hundred and ninety-two serum samples and 54 vitreous samples were collected from patients with a range of eye diseases including neovascular age-related macular degeneration (AMD), diabetic retinopathy, retinal vein occlusion, cataract, glaucoma, dry eye disease, macular hole, epiretinal membranes and intraocular lens (IOL) dislocation. Serum and vitreous samples were analysed for immune globuline (Ig) G ADAs to brolucizumab and ranibizumab using indirect enzyme-linked immunosorbent assay (ELISA). Optical Density (OD) was read at 450 nm (wavelength correction at 550 nm) for ADA level measurements.
Results
Presence of brolucizumab ADAs was observed in patients with and without prior brolucizumab exposure. Both the frequency of notable ADA signals (OD > 0.1) and the mean ADA signal in serum samples were higher for brolucizumab than for ranibizumab. Two patients who experienced severe IOI and occlusive retinal vasculitis following intravitreal brolucizumab had high brolucizumab ADA serum levels. In one of these two patients, high brolucizumab ADA levels were also found in vitreous. Another patient developed moderate IOI without retinal vasculitis in the presence of low brolucizumab ADA serum levels. Overall, notable brolucizumab ADA levels were less frequent in vitreous than in the corresponding serum samples but with a tendency for higher prevalence in vitreous from patients with diabetic retinopathy.
Conclusion
Brolucizumab ADAs occur with significant prevalence in a typical ophthalmic patient population and may represent a risk factor for IOI and occlusive retinal vasculitis following brolucizumab.