Radiation Maculopathy is Anticipated by OCT Hyperreflective Retinal Foci: a Large, Prospective Confirmation study

Purpose: To investigate, by means of spectral domain optical coherence tomography (SD-OCT), retinal reflectivity changes as an early biomarker anticipating radiation induced macular edema (ME) in patients treated by Iodine-125 (I-125) brachytherapy. Methods: Thirty patients planned for I-125 brachytherapy because of uveal melanoma (UM) were prospectively included and followed every 4 months for 5 years. Reflectivity alterations, namely hyperreflective retinal foci (HRF) were characterized and counted by two independent masked examiners by means of SD-OCT imaging. HRF were defined as discrete intraretinal reflectivity changes ≤30μm, with reflectivity similar to nerve fiber layer and without back shadowing. Results: ME occurred in seventeen patients 24.2 ±15.1 months (group 1) after irradiation. Thirteen patients showed no signs of ME at 5-year follow-up (group 2). The number of HRF was statistically higher in sequential visits until the evidence of ME in group 1 vs group 2 (p<0.0001). In group 1, HRF at the follow-up before the evidence of ME were significantly related to the OCT central subfield thickness at ME appearance (P=0.0002, r2=0.6129). The intergrader agreement was almost perfect (ICC=0.80). Conclusions: HRF may be considered as an early in vivo imaging biomarker of retinal inflammatory response to ocular irradiation, anticipating the development of radiation maculopathy.