title: A cross-linked hyaluronic acid hydrogel (Healaflow(®)) as a novel vitreous substitute.
abstract: OBJECTIVE
  Vitrectomy requires the substitution of the natural vitreous, as well as tamponading of retinal breaks. Clinically available alternatives such as gas and silicone oil have side effects such as inflammation, secondary glaucoma, cataract, and a need for head posturing. In this study, a hydrogel of cross-linked sodium hyaluronic acid (Healaflow(®)) is evaluated for use as a novel vitreous substitute.
  
  
  METHODS
  A combined 25-20-gauge pars plana vitrectomy with posterior vitreous detachment was performed in the right eye of twelve pigmented rabbits, with subsequent injection of approximately 1 ml Healaflow(®). Clinical evaluation, measurement of intraocular pressure (IOP), and full-field ERG were performed postoperatively. The rabbits were sacrificed at different time-points between 42 and 105 days. After enucleation, the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy and immunohistochemistry.
  
  
  RESULTS
  Healaflow(®) was successfully used with standard surgical procedures and remained translucent but did lose most of its viscosity during the postoperative period. One rabbit was lost due to unrelated causes. In two eyes iatrogenic partial retinal detachments were seen, and in two eyes significant cataract developed due to intra-operative complications. ERG-recordings revealed no toxic effect on rod or cone function. Routine microscopy and immunohistochemistry demonstrated normal morphology with some Müller cell activation (up-regulation of glial acidic fibrillary protein, GFAP) compared to unoperated eyes and no significant DNA-fragmentation (TUNEL-assay).
  
  
  CONCLUSIONS
  Healaflow® did not affect retinal morphology or function negatively during long-term use as a vitreous substitute, making it highly interesting in this setting. An estimated retention time of a few weeks suggests potential for use as a short-term tamponade. Future work will include an increased ratio of cross-linking to prolong the structural integrity of the gel.
authors.affiliation: Department of Ophthalmology, Lund University Hospital, BMC B11, S-22184, Lund, Sweden. henrik.barth@med.lu.se.
authors.forename: Henrik
authors.identifier: http://orcid.org/0000-0003-4702-0626
authors.initials: H
authors.lastname: Barth
authors.affiliation: Department of Ophthalmology, Faculty of Medicine and Health, Örebro University, Örebro University Hospital, Örebro, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Crafoord
authors.affiliation: Department of Ophthalmology, Lund University Hospital, BMC B11, S-22184, Lund, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Andréasson
authors.affiliation: Department of Ophthalmology, Lund University Hospital, BMC B11, S-22184, Lund, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D001187:Artificial Organs; D001672:Biocompatible Materials; D002072:Butylene Glycols / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D004195:Disease Models, Animal; D004596:Electroretinography; D006820:Hyaluronic Acid; D020100:Hydrogels; D011817:Rabbits; D012160:Retina / Q000502:physiology; D014821:Vitrectomy; D057586:Vitreoretinal Surgery; D014822:Vitreous Body
chemical_list: D001672:Biocompatible Materials; D002072:Butylene Glycols; D003432:Cross-Linking Reagents; D020100:Hydrogels; D006820:Hyaluronic Acid; C014376:1,4-bis(2,3-epoxypropoxy)butane
keywords: Hyaluronic acid; Immunohistochemistry; Vitreoretinal surgery; Vitreous substitute