RESUMEN
Silicone oil droplets have been reported in the eyes of human patients following intravitreous (IVT) injections with several marketed biotherapeutic products. Intravitreous administration of a novel biotherapeutic in a 14-week cynomolgus monkey study using insulin syringes was associated with 2, non-test-article-related phenomena: "vitreous floater/clear sphere" on indirect ophthalmoscopy and intrascleral "foreign material near injection track" on histopathology. Retrospective analysis of 81 other preclinical studies of IVT administration of novel biotherapeutics found a greater frequency of clear spheres in monkey IVT studies using insulin syringes and formulations containing polysorbate. We were able to correlate microscopic findings of clear circular to oval areas in the sclera near the injection track with an energy-dispersive X-ray spectroscopy (EDS) signal for silicon at the same location in the sclera. These observations provide further evidence that silicone lubricant in insulin syringes/needles is the source of clear spheres noted in the vitreous and foreign material noted near the injection track in the sclera. Although considered inert and toxicologically insignificant, silicone deposition within the eye should form part of the risk-benefit equation in a clinical setting.