Abstract
Purpose:
To evaluate in vivo the presence of intraretinal hyperreflective spots in eyes with radiation induced maculopathy.
Methods:
25 subjects affected by maculopathy secondary to eye irradiation for a primary intraocular uveal melanoma were enrolled. Diabetic retinopathy, retinal vascular disorders, intraocular inflammation and previous treatment with any intraocular drug were the main exclusion criteria. All eyes previously underwent Iodine125 brachytherapy with a standard apex dose (85 Gy at tumor apex). Macula was never directly included in the irradiation field. Full ophthalmic examination, including spectral domain-OCT (SD-OCT) and fluorescein angiography, was 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 (ONL). Hyperreflective spots were analyzed in a full retinal section both in the foveal area, and between 500 and 1500 µm from the foveal center. All examinations were performed twice, by two independent masked graders.
Results:
The inter-grader agreement was at least substantial for all measurements. In all studied eyes hyperreflective spots were detected by SD-OCT. Hyperreflective spots were mainly located in the inner retina (ILM+RNFL and INL+OPL) compared to the outer retina (ONL) (p<0.005), and their expression significantly progressed with the progression of macular (radiation induced) edema (p= 0.002).
Conclusions:
The presence of retinal discrete microaggregates appearing, on SD-OCT, as hyperreflective spots may represent an in vivo biomarker of retinal microglia activation in radiation maculopathy, as previoulsy shown in other macular disorders. The increase in number and the migration toward outer retinal layers of the (hyperreflective) microaggregates mirrors more severe stages of maculopathy, and confirms the importance of neuroinflammation in the development and progression of radiation-induced maculopathy. This aspect may be related to the so-called senescence process induced by irradiation of solid (intraocular) tumors. This phaenomenon may offer more tailored approaches for the treatment of radiation induced maculopathy.
Keywords: 585 macula/fovea •
671 radiation therapy •
595 microglia