Assessing Retrobulbar Hyaluronidase as a Treatment for Filler-Induced Blindness in a Cadaver Model

Abstract

Background: Retrobulbar injection of hyaluronidase is a proposed but unproven treatment for blindness induced by hyaluronic acid gel fillers. This study examines the viability of this treatment by determining whether hyaluronidase can diffuse through the dural sheath of the optic nerve to clear a filler-mediated occlusion of the central retinal artery. Methods: Six human cadaveric optic nerves were studied in vitro. One optic nerve was selected as a control and maintained at physiologic temperature, without any exposure to hyaluronic acid gel or hyaluronidase. Another optic nerve was randomly selected to simulate the filler-induced central retinal artery occlusion with subsequent retrobulbar hyaluronidase injection. To simulate a central retinal artery occlusion, this experimental nerve and additional controls were injected with hyaluronic acid gel. These hyaluronic acid gel–injected nerves were then either injected directly with hyaluronidase to establish a control for intraneural hyaluronidase exposure, or immersed in undiluted hyaluronidase to simulate retrobulbar hyaluronidase injection. To control for passive diffusion of hyaluronic acid gel from neural parenchyma, one nerve was immersed in saline. Following fixation, the nerves were grossly and microscopically assessed for the quantity and distribution of hyaluronic acid. Results: Intact hyaluronic acid gel was observed grossly and microscopically in the control optic nerves injected directly with filler and not with hyaluronidase. The control optic nerve injected with intraneural hyaluronidase exhibited partial digestion of the filler. Immersion in undiluted hyaluronidase led to no apparent gross or microscopic digestion of injected intraneural hyaluronic acid gel. Conclusion: Hyaluronidase does not demonstrate the ability to cross the dural sheath of the optic nerve, suggesting that retrobulbar hyaluronidase injection is unlikely to alleviate hyaluronic acid gel–mediated central retinal artery occlusion and blindness.

The interaction between hyaluronidase and hyaluronic acid gel fillers - a review of the literature and comparative analysis

“…Hyaluronidase is a naturally occurring enzyme that catalyzes the degradation of HA by hydrolyzing the bond between N-acetylglucosamine and glucuronic acid [4,5] . In addition to its offlabel use as a subcutaneous adjuvant that increases the dispersion of drugs, it has been shown to be effective in both reversing the volumetric effects of HA filler injections and treating local ischemic complications [6][7][8][9] , although the reversibility of HA filler associated blindness with hyaluronidase has not been established [10,11] . Understanding the interactions between the various fillers and the enzymes available for dissolution might optimize outcomes in the event of a filler misplacement or occlusive event.…”

The 10-Point Plan 2021: Updated Concepts for Improved Procedural Safety During Facial Filler Treatments

“…There is currently a lack of indisputable evidence for reversal of injection-related visual compromise (IRVC), with conflicting reports regarding the merits of retrobulbar, supraorbital, and supratrochlear hyaluronidase and an urgent need for multidisciplinary collaboration. 85 Many studies are flawed by incomplete documentation. It is imperative that vision is documented upfront in order to establish prognosis.…”

Periocular rejuvenation using hyaluronic acid fillers

“…In another study by Paap et al [27] the effectiveness of retrobulbar hyaluronidase was investigated in a human cadaver model. In this study, the authors demomstrated that retrobulbar hyaluronidase injection is unlikely to be effective in management of HA filler induced central retinal artery occlusion and blindness due to its inability to cross dural sheet of the optic nerve.…”