Dataset Information

Changes in choroidal vascular structure from vitreoretinal lymphoma and the intraocular cytokine level associated with clinical resolution after intravitreal methotrexate treatment

ABSTRACT:

Purpose

To evaluate changes in choroidal vascular structure and aqueous cytokine levels in eyes with vitreoretinal lymphoma (VRL) after intravitreal methotrexate (MTX) treatment.

Methods

In this retrospective study, VRL patients who visited our hospital between October 2018 and July 2020 were reviewed. Aqueous samples were obtained before treatment and at clinical resolution after intravitreal MTX therapy. Interleukin (IL)-6 and IL-10 levels and the IL-10-to-IL-6 ratio were evaluated. Swept-source optical coherence tomographic images were obtained along with the aqueous samples. Subfoveal choroidal thickness (SFCT), total vascular area of the choroid (TCA), stromal area (SA), luminal area (LA), and choroidal vascularity index (CVI) were assessed.

Results

Twelve patients were enrolled (female:male—5:7). The mean age (± standard deviation) at diagnosis was 60.9±8.5 years. In the 16 eyes diagnosed with VRL, values of SFCT, TCA, LA, and SA significantly decreased after treatment (all p-values <0.05). Additionally, the aqueous cytokine IL-10 level and IL-10-to-IL-6 ratio were significantly decreased (p = 0.001 and p = 0.003, respectively). The choroidal structure in the non-treated fellow eyes did not show any significant difference. There were no further changes in SFCT, TCA, LA, or CVI that occurred during maintenance therapy. For clinical remission, the patients received 7.7±5.5 intravitreal MTX injections. The required number of injections for clinical remission was positively correlated with best-corrected visual acuity, IL-10, and IL-6 levels in the active phase (p = 0.035, p = 0.009, and p = 0.031, respectively).

Conclusion

Eyes with active VRL exhibited choroidal thickening with increased vascular and stromal areas that decreased after remission following MTX treatment. Higher aqueous IL-10 and IL-6 levels and lower visual acuity in the active phase may indicate the number of injections required for remission; this should be considered in the treatment of patients with VRL.

SUBMITTER: Kim R

PROVIDER: S-EPMC8610271 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo seek novel diagnostic approaches, we improved the workflow of cell-free DNA (cfDNA) sequencing and evaluated its feasibility in vitreoretinal lymphoma (VRL) specimens; the profile of mutations was preliminarily analyzed for potential diagnostic value.MethodsThe study was a diagnostic trial. 23 eyes of 23 patients with VRL and 25 eyes of 25 patients with inflammatory eye diseases were enrolled. Approximate 500μl undiluted vitreous humor and 10ml diluted vitreous fluid was obtained through diagnostic vitrectomy and sent for cytopathological examinations. 500μl of the diluted vitreous fluid was spared for cfDNA sequencing. For cfDNA sequencing, DNA fragmentation procedure was added to the workflow to improve the extraction efficiency; mutations detected were analyzed for potential diagnostic model. The sensitivity and specificity of the cytopathology and cfDNA sequencing were compared. The clinical manifestations were preliminarily analyzed for potential correlations with the genotypes.ResultsCfDNA sequencing was accomplished in 23 eyes with VRL and 20 eyes with inflammatory eye diseases. VRL-related mutated genes included MYD88 (18 eyes, 78%), ETV6 (11 eyes, 48%), PIM1 (11 eyes,48%), BTG2 (7 eyes, 30%), IRF4 (7 eyes, 30%), CD79B (6 eyes, 26%), LRP1B (6 eyes, 26%), etc. Logistic regression based on the mutations of MYD88 and ETV6 was of the potential for the diagnosis of VRL (P<0.001, adjusted R2 = 0.789, sensitivity 0.913, specificity 0.950); by comparison, the sensitivity and specificity of the vitreous cytopathology were 0.826 and 1.000, respectively. Further analysis of the mutation profile showed that patients carrying CD79B mutation tended to have higher intraocular interleukin-10 level (P=0.030), that CARD11 mutation was correlated with younger age at ocular onset (P=0.039), and that patients with intracranial involvement carried more multiple-site mutations in the BTG2 gene (P=0.013).ConclusionsThe improved workflow of CfDNA sequencing is of sound feasibility in a limited amount of vitreous humor. The logistic model based on the mutations could help to provide reliable clues for the diagnosis of VRL.