PurposeTo investigate the safety of blue light scleral cross-linking (SXL) by evaluating changes in biological parameters in the retina and choroid in the eyes of rhesus macaques (Macaca mulatta).MethodsFifteen 3-year-old macaques (30 eyes) were randomly divided into three groups (n=5). SXL was performed via riboflavin (0.5%) and blue light (460nm) at the location of the equatorial sclera. Right eyes served as experimental eyes, and left eyes as control eyes. One quadrant of each right eye was irradiated in group A, two quadrants of each right eye and one quadrant of each left eye were irradiated in group B, and two quadrants of each right eye were irradiated in group C. Optical coherence tomography, optical coherence tomography angiography, and flash electroretinography (f-ERG) examinations were performed at baseline and 1week, 1month, 3months, and 6months after SXL. Additionally, retinal tissue alterations were detected via transmission electron microscopy at 1week postoperatively.ResultsThere were no significant differences between experimental eyes and control eyes in retinal thickness, vessel density of retinal superficial capillary plexus, and choroid thickness in any of the groups at any of the time points investigated (p>0.05). Significant reductions in f-ERG parameters were detected 1week postoperatively in the experimental eyes of groups A and C (p<0.05), but they gradually recovered, and there was no significant difference 1month postoperatively (p>0.05). Ultrastructural changes were evident in the retinal layers of SXL eyes. In group B, there were no significant differences between the right and left eyes at any of the follow-up time points investigated.ConclusionsBlue light SXL can cause transient retina damage. The f-ERG parameters reductions and retinal ultrastructural changes were found at early stage, even though there were not significant changes in retinal thickness, vessel density of retinal superficial capillary plexus, and choroid thickness after blue light SXL. The long-term intraocular safety of the blue light SXL technique should be investigated further.