Replacement of the liquid vitreus with sodium hyaluronate in monkeys

Denlinger, Janet L.; El-Mofty, Aly A.M.; Balazs, Endre A.

doi:10.1016/0014-4835(80)90093-7

Cited by 52 publications

(9 citation statements)

References 6 publications

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“…Chemically different compounds such as hyaluronic acid (Healon R ), perfluorinated organic liquids and various synthetic polymers have been tested in the laboratory (Denlinger et al 1980, 1980b, Koster et al 1986, 1986b A fairly recent idea is to explore substances used successfully in other surgical areas (Yang et al 2008). One potential compound is the acrylamide-derivative Bio-Alcamid ® (Polyalkylimide), a clear hydrogel used as subcutaneous filler in reconstructive plastic surgery (Lahiri et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Experimental vitreous tamponade using polyalkylimide hydrogel

Crafoord

Andréasson

Ghosh

2011

Graefes Arch Clin Exp Ophthalmol

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Purpose: To evaluate polyalkyl-imide as a possible vitreous tamponading agent. Methods:A 20 gauge pars plana vitrectomy and posterior vitreous detachment were performed in the right eye of six pigmented rabbits. Approximately 1 ml of viscoelastic gel, polyalkyl-imide (Bio-Alcamid ® ) was thereafter injected into the vitreous space. Full-field ERG and intraocular pressure (IOP, Tonopen) was measured pre-and postoperatively at regular intervals up to 28 days. At day 6 or 28, the rabbits were sacrificed and the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy. Results:The viscoelastic hydrogel was successfully injected and remained translucent with preserved gel properties throughout the postoperative period. The postoperative IOP was unchanged compared to preoperative values. Five of six eyes displayed retinal edema or pigmentary changes centrally while the periphery appeared intact. ERG recordings showed a radical decrease in rod and cone derived B-wave amplitudes. Histological examination confirmed varying degrees of edema combined with neuronal cell death within the retinal layers in the central part of the fundus while the peripheral part appeared intact. Conclusion:Polyalkyl-imide displays favourable physical properties when used as a vitreous tamponade. However, the hydrogel causes functional and morphological retinal damage when in direct contact with the inner retina. Possible pathological mechanisms include osmotic imbalance and direct toxic effects, and modification of biochemical properties is warranted before clinical use will be possible.

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Section: Introductionmentioning

confidence: 99%

Experimental vitreous tamponade using polyalkylimide hydrogel

Crafoord

Andréasson

Ghosh

2011

Graefes Arch Clin Exp Ophthalmol

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“…[3][4][5] The inflammatory effects of endotoxin are well described, and it is often used to produce experimental animal models of uveitis following ITV in mice, 6 rabbits, [7][8][9][10][11] pigs, 12 and monkeys. 13 Clinically, cases of acute postoperative sterile uveitis or toxic anterior segment syndrome have been linked to endotoxin contamination of ophthalmic devices. [14][15][16] Additionally, therapeutic biologics for intravitreal administration may be at increased risk for contamination with endotoxin or other biologic impurities, particularly if they are produced in prokaryotic expression systems.…”

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confidence: 99%

Determination of a No-Observable Effect Level for Endotoxin Following a Single Intravitreal Administration to Dutch Belted Rabbits

Bantseev¹,

Miller

Bentley

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to characterize the inflammatory response and determine a no-observable effect level (NOEL) in rabbit eyes after endotoxin intravitreal (ITV) injection.METHODS. Fifty-three naïve male Dutch Belted rabbits were treated with a single 50-lL ITV injection ranging from 0.01 to 0.75 endotoxin units/eye (EU/eye) and monitored for up to 42 days post treatment. Ophthalmic examination included slit-lamp biomicroscopy and indirect ophthalmoscopy. Laser flare photometry was performed in a subset of animals. On days 2, 8, 16, and 43, a subset of animals was necropsied and eyes processed for histopathological evaluation.RESULTS. Intravitreal injection of endotoxin at ‡0.05 EU/eye resulted in a dose-related anterior segment inflammation response. No aqueous flare or cell response was noted in the 0.01 EU/ eye dose group. A more delayed posterior segment response characterized by vitreal cell response was observed beginning on day 5, peaking on day 9, and decreasing starting on day 16 that persisted at trace to a level of 1þ on day 43. Microscopy findings of infiltrates of minimal mixed inflammatory cells in the vitreous and subconjunctiva and proteinaceous fluid in the anterior chamber and/or vitreous were observed in eyes given ‡0.1 EU/eye. CONCLUSIONS.We defined the NOEL for ITV endotoxin to be 0.01 EU/eye, suggesting that the vitreal cavity is more sensitive to the effects of endotoxin than the anterior segment and aqueous chamber. These data highlight the importance of assessing endotoxin level in intravitreal formulations, as levels as low as 0.05 EU/eye may confound the safety evaluations of intravitreal therapeutics in rabbits.

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“…The use of derivates of sodium hyaluronic acid in vitreoretinal surgery predates their ubiquitous use in cataract and anterior segment surgery [12,14,[40][41][42], but their use in a clinical setting has been limited mainly due to concern about short term side effects and retention time [41,43]. Healaflow® is a commercially available compound consisting of a cross-linked sodium hyaluronic acid hydrogel and is FDA approved for use in glaucoma surgery [22,23].…”

Section: Our Previous Results and Our Hypothesismentioning

confidence: 99%

“…Early attempts were made to transplant animal and human vitreous [11] and investigations have been made into numerous semisynthetic [12][13][14] and synthetic [15] molecules, although few of them have reached a clinical setting and none have fulfilled the requirements for long-term biocompatibility.…”

Section: Introductionmentioning

confidence: 99%

A new model for in vitro testing of vitreous substitute candidates

Barth

Crafoord

O’Shea

et al. 2014

Graefes Arch Clin Exp Ophthalmol

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Purpose To describe a new model for in vitro assessment of novel vitreous substitute candidates. Methods The biological impact of three vitreous substitute candidates was explored in a retinal explant culture model; a polyalkylimide hydrogel (Bio-Alcamid®), a two component hydrogel of 20 wt.% poly (ethylene glycol) in phosphate buffered saline (PEG) and a cross-linked sodium hyaluronic acid hydrogel (Healaflow®). The gels where applied to explanted adult rat retinas and then kept in culture for 2, 5 and 10 days. Gel-exposed explants were compared with explants incubated under standard tissue culture conditions. Cryosections of the specimens were stained with hematoxylin and eosin, immunohistochemical markers (GFAP, Vimentin, Neurofilament 160, PKC, Rhodopsin) and TUNEL. Results Explants kept under standard conditions as well as PEG-exposed explants displayed disruption of retinal layers with moderate pyknosis of all neurons. They also displayed moderate labeling of apoptotic cells. Bio-Alcamid®-exposed explants displayed severe thinning and disruption of retinal layers with massive cell death. Healaflow®-treated explants displayed normal retinal lamination with significantly better preservation of retinal neurons compared with control specimens, and almost no signs of apoptosis. Retinas exposed to Healaflow® and retinas kept under standard conditions showed variable labeling of GFAP with generally low expression and some areas of upregulation. PEG-exposed retinas showed increased GFAP labeling and Bio-Alcamid®-exposed retinas showed sparse labeling of GFAP. Conclusions Research into novel vitreous substitutes has important implications for both medical and surgical vitreoretinal disease. The in vitro model presented here provides a method of biocompatibility testing prior to more costly and cumbersome in vivo experiments. The explant culture system imposes reactions within the retina including disruption of layers, cell death and gliosis, and the progression of these reactions can be used for comparison of vitreous substitute candidates. Bio-Alcamid® had strong adverse effects on the retina which is consistent with results of prior in vivo trials. PEG gel elicits reactions similar to the control retinas whereas Healaflow® shows protection from culture-induced trauma indicating favorable biocompatibility.

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Replacement of the liquid vitreus with sodium hyaluronate in monkeys

Cited by 52 publications

References 6 publications

Experimental vitreous tamponade using polyalkylimide hydrogel

Experimental vitreous tamponade using polyalkylimide hydrogel

Determination of a No-Observable Effect Level for Endotoxin Following a Single Intravitreal Administration to Dutch Belted Rabbits

A new model for in vitro testing of vitreous substitute candidates

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