In fact a study evaluating the biocompatibility of intravitreal hyaluronic acid implants found that there were no evident signs of inflammation following implantation. These results suggest that HA particles are good nanocarriers for posterior drug delivery. To find the cause for particle implant-mediated IOP reduction, we first observed the distribution of the implants following intravitreous implantation. Although extensive research efforts have been placed on the development of nanocarriers for anterior and posterior ocular drug delivery, little has been done to study the fate of particle implants following injection. Briefly, these studies have revealed that nano and microparticles can reach the intraocular tissues when administered systemically or through periocular administration routes. However, it has also been reported that systemic administration of drug requires high doses to offset loss due to non-specific targeting and systemic side effects. Our studies revealed that, rather surprisingly, majority of the particle implants injected intravitreally, only stay in the posterior segments for a very short period of time. These results support that that, differing from common assumption that intravitreous administration will lead to better distribution, humor flow actively pushed particle implants out of the posterior. In addition, particle implants may reach retinal tissues shortly after intravitreous injection. Although the fate of the particles is yet to be determined, it is plausible that most of the particle implants exit the posterior chamber via the trabecular meshwork based on the fluorescent intensity distribution. This observation is supported by several earlier observations that particles and drugs may leave vitreous compartment via the trabecular meshwork. Particle implants have been shown to trigger immune reactions in the surrounding tissues, and it is LY2109761 700874-71-1 likely that similar particle-mediated tissue responses are also found in ocular tissues. To the best of our knowledge, very few studies have been done in this regard. A few studies have tested poly following intravitreal injection and found no evident signs of inflammatory reaction up to 3 months. Studies involving PLGA microspheres, and porous silicon microparticles, found that they were well tolerated with no clinical signs of inflammation based on visual examination even four days to four months after implantation. A recent study has also evaluated the ocular compatibility of gluteraldehyde crosslinked and EDAC crosslinked hyaluronic acid implants in the anterior chamber and found that EDAC crosslinked implants were more compatible. However, it is mostly unclear whether the intravitreous implantation of particles would trigger immune reactions in different ocular tissues, including cornea, iris, retina and trabecular meshwork. To our surprise, we found that all the tested particle implants had no significant influence on the morphology and anatomical structure of cornea, iris, retina tissue despite of apparent short term accumulation of particle implants in nearby retinal tissue. It is well established that trabecular meshwork and surrounding ciliary body is responsible for maintaining the IOP. To search for the cause of IOP changes following particle implantation, we examined the tissue responses in the trabecular meshwork.