Abstract
Purpose:
To evaluate in vivo if retinal microglia activity mirrors the progression of diabetic retinopathy (DR).
Methods:
40 subjects were enrolled: 30 subjects were affected by diabetes mellitus and 10 normals served as controls. Proliferative DR, previous laser photocoagulation, intraocular surgery or intravitreal injection, glaucoma or ocular hypertension and neurodegenerative diseases were the main exclusion criteria. One eye of each subject was used for statistical analysis. Among diabetic patients: 10 patients had mild non proliferative DR (Mi-NPDR), 10 moderate NPDR (Mo-NPDR group) and 10 severe NPDR (Se-NPDR). Full ophthalmic examination including spectral domain-OCT (SD-OCT) were performed in all eyes. After segmentation of retinal layers by SD-OCT, retinal images were analyzed for reflectivity changes (hyperreflectivity spots) at the level of: internal limiting membrane plus retinal nerve fiber layer (ILM+RNFL), inner nuclear layer plus outer plexiform layer (INL + OPL) and outer nuclear layer, where glial cells are located in the human retina. Hyperreflective sposts were analyzed in a full retinal section between 500 and 1500 µm from the foveal center. All examinations were performed twice, by two independent masked graders.
Results:
No statistically significant differences were found for age among all groups and for glycemic control between diabetic groups. The inter-grader agreement was at least substantial for all measurement. In DR eyes hyperreflective spots (discrete microaggregates) were systematically detected at the level of ILM+RNFL (75% vs 87% vs 98% in Mi-NPDR vs Mo-NPDR vs Se-NPDR, respectively; p<0.0001) and their expression significantly progressed toward outer retinal layers with the progression of NPDR steps (p< 0.005 for INL+OPL in the three groups; p< 0.001 for ONL in the three DR groups).
Conclusions:
The presence of retinal discrete microaggregates, documented as hyperreflective spots, in areas corresponding to microglial cells may represent an in vivo biomarker of retinal microglial activation in diabetes. The increase in number and the significant migration toward outer retinal layers of the (hyperreflective) microaggregates, mirrors the progression of DR, confirming the importance of neuroinflammation in the development and progression of DR. Microglial activation may be detected by spectral domain OCT using refined retinal layers analysis.
Keywords: 499 diabetic retinopathy •
595 microglia •
552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)