In Vitro Epiretinal Membrane Model and Antibody Permeability: Relationship With Anti-VEGF Resistance in Diabetic Macular Edema.

Purpose: Diabetic macular edema (DME) is characterized by an accumulation of fluid in the macula due to diabetic retinopathy. Currently, anti-VEGF drugs are the standard treatment worldwide for DME. This study aimed to assess whether the existence of epiretinal membrane (ERM) affects anti-VEGF efficacy, due to reduced permeability of the antibody through the ERM. Methods: We retrospectively examined clinical data of DME patients who underwent anti-VEGF treatment and evaluated whether clinical differences existed between DME eyes with ERM and those without ERM. We then created an in vitro ERM model using MIO-M1, ARPE-19, and NTI-4 cells on Transwell membranes and evaluated antibody permeability through this in vitro ERM model using fluorescently labeled antibodies. Results: Central retinal thickness (CRT) change between before and 1 month after first anti-VEGF treatment, as well as final CRT and final visual acuity 12 months after first anti-VEGF treatment, significantly differed between DME eyes with ERM and those without ERM. The in vitro ERM model led to production of collagen I in a manner similar to that of human ERM specimens. Fluorescence intensity of the lower chamber of the in vitro ERM model was significantly reduced in a dose-dependent manner. Conclusions: Clinical data analysis indicated that the existence of ERM in DME eyes lowered the efficacy of anti-VEGF treatment. Reduced antibody permeability through the in vitro ERM model suggested ERM presence was associated with resistance to anti-VEGF treatment in DME eyes with ERM.

Biological Characteristics of Subsilicone Oil Fluid and Differences With Other Ocular Humors.

PURPOSE: Subsilicone oil fluid (SOF) in eyes with silicone oil (SO) endotamponade possibly has a role in complications (e.g., vision loss); thus, we aimed to examine inflammatory cytokine and electrolyte levels and retinal glial cell viability in SOF. METHODS: We measured major inflammatory cytokine levels and electrolytes in SOF and compared them with those in vitreous fluid (VF) and anterior chamber fluid (ACF). We analyzed the correlation between inflammatory cytokines and retinal thickness in SO-filled eyes. Further, we measured the MIO-M1 cell viability in medium with SOF and compared it with that containing VF. RESULTS: We collected and examined 57 SOF, 22 ACF, and 21 VF samples from eyes with PVR, PDR, RD, and MH. Interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 levels in SOF were significantly higher than those in ACF. There was no significant difference for all cytokines between SOF and VF. Retinal thickness changes during SO endotamponade were not correlated with the presence of any inflammatory cytokines. Levels of ferrous iron, but not of potassium, showed a significant decrease in SOF compared with VF. The WST-1 assay showed that SOF-added medium induced higher MIO-M1 cell viability than VF-added medium. CONCLUSIONS: We found no significant correlation between the change in the retinal thickness and cytokine levels, but SOF contains higher concentrations of cytokines and lower concentrations of ferrous iron and can be biologically distinguished from ACF and VF. TRANSLATIONAL RELEVANCE: Novel knowledge of inflammatory cytokine levels and electrolytes in SOF provides better understanding of pathology of SO-filled eyes.

Silicone oil-associated retinal light exposure under a surgical microscope.

PURPOSE: Based on the hypothesis that silicone oil (SO) with a higher refractive index than water induces unexpected vignetting effects during surgeries, we aimed to investigate the relationship between the volume of SO and light intensity using a surgical microscope. METHODS: Using a light-sensitive paper and model eye filled with varying volumes (0%, 50%, 62.5%, 75%, 87.5% and 100%) of SO, the light intensity of intraocular lens (IOL) with various refractive powers (0, 10 and 20 dioptres) illuminated by a surgical microscope was measured. RESULTS: Light exposure density with 1.0% coaxial and oblique light was approximately 22-fold higher than that with 0.1% coaxial and oblique light. Further, it was approximately 34-fold higher in eyes with +20 D IOL than in those with no IOL. The density in eyes with 75% SO was the highest among all groups followed by that with 0% SO. Light exposure densities in the eyes with 75% and 0% SO were significantly higher than those with other volumes of SO. In SO-filled eyes, a microscope set with only an oblique light and a filter successfully reduced light exposure. CONCLUSION: Silicone oil-related vision loss (SORVL) during SO removal surgeries might be due to increased light exposure on the macular retina caused by the SO-associated vignetting effect. SORVL could be prevented by placing a filter in the microscope during SO removal surgeries.