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Pro-Permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; the Ozurdex for Retinal Vein Occlusion (ORVO) Study.

ABSTRACT: PURPOSE:To correlate aqueous vasoactive protein changes with macular edema after dexamethasone implant in retinal vein occlusion (RVO). DESIGN:Prospective, interventional case series. METHODS:Twenty-three central RVO (CRVO) and 17 branch RVO (BRVO) subjects with edema despite prior anti-vascular endothelial growth factor (VEGF) treatment had aqueous taps at baseline and 4 and 16 weeks after dexamethasone implant. Best-corrected visual acuity (BCVA) and center subfield thickness were measured every 4 weeks. Aqueous vasoactive protein levels were measured by protein array or enzyme-linked immunosorbent assay. RESULTS:Thirty-two vasoactive proteins were detected in aqueous in untreated eyes with macular edema due to RVO. Reduction in excess foveal thickness after dexamethasone implant correlated with reduction in persephin and pentraxin 3 (Pearson correlation coefficients = 0.682 and 0.638, P = .014 and P = .003). Other protein changes differed among RVO patients as edema decreased, but ?50% of patients showed reductions in hepatocyte growth factor, endocrine gland VEGF, insulin-like growth factor binding proteins, or endostatin by ?30%. Enzyme-linked immunosorbent assay in 18 eyes (12 CRVO, 6 BRVO) showed baseline levels of hepatocyte growth factor and VEGF of 168.2 ± 20.1 pg/mL and 78.7 ± 10.0 pg/mL, and each was reduced in 12 eyes after dexamethasone implant. CONCLUSIONS:Dexamethasone implants reduce several pro-permeability proteins providing a multitargeted approach in RVO. No single protein in addition to VEGF can be implicated as a contributor in all patients. Candidates for contribution to chronic edema in subgroups of patients that deserve further study include persephin, hepatocyte growth factor, and endocrine gland VEGF.

SUBMITTER: Campochiaro PA

PROVIDER: S-EPMC6600806 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRetinal vein occlusion (RVO) is the second most common vision-threatening retinal vascular disease. Intravitreal dexamethasone implant has been applied to treat macular edema secondary to RVO (RVO-ME). However, the alteration of morphologic features detected with optical coherence tomography angiography (OCTA) has not been fully studied in RVO-ME patients before and after the treatment.ObjectiveThis study is aimed at identifying potential therapeutic targets in RVO with integrative bioinformatic analysis and compares the OCTA characteristics alterations in patients with RVO-ME receiving injection of dexamethasone intravitreal implant.MethodsBioinformatic analysis was analyzed in GSE101398 dataset from the Gene Expression Omnibus database. Multiple functional enrichment analyses were performed, and protein-protein interaction network was constructed to visualize the key node genes. Eleven eyes with RVO-ME were examined with OCTA before and after intravitreal dexamethasone implant. The OCTA parameters, including macular thickness, vessel density, foveal avascular zone parameters, the number of hyperreflective foci (HRF), area of cystoid edema, and subretinal fluid (SRF), were compared. The correlation was analyzed between best-corrected visual acuity (BCVA) and OCTA parameters.ResultsA total of 79 differentially expressed genes were identified. Functional enrichment analyses revealed the enriched inflammatory events in RVO. In RVO-ME, Pearson correlation revealed that baseline BCVA was positively correlated with the area of SRF and central macular thickness, while no correlation was detected between baseline BCVA and HRF number or the area of cystoid edema. The visual acuity improved, and the central macular thickness was decreased after intravitreal dexamethasone implant injection. Besides, the number of HRF, the area of cystoid edema, and SRF were significantly alleviated after dexamethasone intravitreal injection.ConclusionRetinal inflammation plays a crucial role in RVO pathogenesis. The imaging biomarkers of RVO including Müller glial intracellular edema, and retinal pigment epithelium dysfunction, could be assessed in OCTA and attenuated by intravitreal dexamethasone implant effectively.

Project description:Purpose:To evaluate retinal functional improvement by means of visual acuity and retinal sensibility examination after intravitreal dexamethasone implant in patients affected by cystoid macular edema secondary to retinal vein occlusion. Methods:Twenty-six consecutive patients affected by retinal vein occlusion complicated by cystoid macular edema were enrolled in this prospective interventional study. All patients underwent a baseline complete ophthalmological evaluation as well as retinal angiography, OCT examination, and microperimetry evaluation. Each patient was treated with intravitreal injection of a long-term steroid implant (Ozurdex, Allergan). Follow-up evaluations were performed at months 1, 3, and 6 and completed by OCT and MP1 examination. Clinical data underwent statistical analysis. Results:Baseline functional evaluation showed mean visual acuity of 0,63±0,42 LogMAR and retinal sensitivity of 7,93±4,73?dB (mean±standard deviation); after treatment, at day 30 we found, respectively, 0,43±0,38 LogMAR (p<0.05, compared to baseline) and 10,15±4,410?dB (p<0.05); at day 90, we found 0,44±0,32 (p<0.05) and 9.61±4,29?dB (p<0.05); at day 180, we found 0,41±0,31 (p<0.05) and 9,95±3,79?dB (p<0.05). Fixation pattern improved significantly (p<0.05), showing a stable fixation in 30% of patients at baseline, increasing to 77% of patients at day 180. Baseline morphological evaluation showed a central retinal thickness (CRT) of 398,21±181,65??m after treatment; we found a CRT of 222,64±95,21??m at day 30 (p<0.05, compared to baseline), 307,50±120,25??m (p<0.05) at day 90, and 294,93±135,86??m (p<0.05) at day 180. About 15,3% patients showed already at month 3 a recurrence of macular edema. They underwent a retreatment before month 6 as for treatment guidelines. Conclusion:Our detailed analysis showed the significative increase in retinal function in the early phases of the follow-up. Retinal sensibility showed a stronger correlation than VA in macular edema reabsorption, better underlying the progressive functional recovery and increase in quality of vision and life for the patients. This trial is registered with ClinicalTrials.gov NCT03559491.

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Pro-Permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; the Ozurdex for Retinal Vein Occlusion (ORVO) Study.

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