Rheologic Characterization of Ophthalmic Viscosurgical Devices Containing Sodium Hyaluronate and Sodium Chondroitin Sulf

1. Masoud Jafari, PharmD, PhD Alcon Research Ltd, Fort Worth, Texas, USA and Steve A. Arshinoff, MD Humber River Regional Hospital, University of Toronto, Toronto, Canada, & McMaster University, Hamilton, Ontario, Canada Rheologic Characterization of Ophthalmic Viscosurgical DevicesContaining Sodium Hyaluronate and Sodium Chondroitin Sulfate Disclosures: Dr. Jafari is an employee of Alcon and Dr. Arshinoff is a consultant to Alcon. Alcon funded this study and provided assistance with the preparation of this ePoster.

2. Introduction • Background • Subjectively, surgeons understand how the intraoperative “feel” of one ophthalmic viscosurgical device (OVD) differs from another, but • Quantitative descriptions of the physical characteristics of OVDs assist surgeons to understand OVDs better, and provide critical information to help companies improve OVDs. • ObjectiveThe purpose of this study was to evaluate various OVDs containing sodium hyaluronate or containing both sodium hyaluronate and chondroitin sulfate, in terms of: • Rheological properties (related to deformation and flow), and • Cohesive/dispersive properties (related to whether an OVD holds together or can be easily pulled apart).

3. Methods I Rheology: • Some OVDs behave like a fluid when manipulated, but then settle into a nearly solid state when at rest; these characteristics indicate pseudoplasticity. • To test whether OVDs behaved more like liquids or more like solids under various conditions, we used a Bohlin Controlled Stress Rheometer (Bohlin Rheologic AB; Lund, Sweden), at the standard and surgically relevant temperature of 25 °C, to test • OVD viscosities under zero shear (ie, at rest), and • OVD viscosities under shear rates from 0.001 seconds-1 (very slow) to 1000 seconds-1 (very fast), to yield a pseudoplasticity curve

4. Methods II Cohesion/Dispersion Evaluation: OVDs were evaluated in terms of the Cohesion-Dispersion Index, which is • A value between 0 (very dispersive) and100 (very cohesive) • Reported as the % OVD aspirated/ 100 mm Hg • Derived by testing how much ofa 0.5-ml sample of OVDis aspirated into a pipette tipwhen a given amount ofvacuum is applied,using the automated modelas described in the referenced article.1 vacuum line pipette tip OVD  1. Poyer JF, Chan KY, Arshinoff SA. Quantitative method to determine the cohesion of viscoelastic agents by dynamic aspiration. J Cataract Refractive Surg. 1998:24(8);1130-1135

5. Materials: OVDs Evaluated Beyond differences in polysaccharide content as shown above,these OVDs also differ in their excipients, such as salts. *We had intended to test Chondrovisc® OVD, but samples from the Turkish manufacturer (AkAkinIlac San) were not available to us in the US.

6. Results: Cohesion–Dispersion Index  100 = max cohesive  0 = max dispersive More Dispersive More Cohesive

7. Results: Zero-Shear Viscosity Less Viscous More Viscous

8. Results: Rheological Profiles • The figure below shows how viscosity decreased as shear rate increased for the OVDs containing hyaluronic acid (HA) or containing both HA and chondroitin sulfate (CS): • The 2 OVDs without CS and with high-molecular-weight, low-concentration HA (Opegan Hi®OVD and Healon®OVD) were most susceptible to shear thinning (curves begin to drop with a steeper slope at arrows). • The OVD without CS and with low-molecular-weight, high-concentration HA (Vitrax®OVD) had the lowest viscosity at low shear, and low shear thinning. • The 3 OVDs with both HA and CS (DisCoVisc® OVD, Viscoat®OVD, and Ixium® HCS OVD) had intermediate viscosity at low shear and were resistant to shear thinning. ↓Lessviscous(morethinning)↓ Ixium® HCS

9. Discussion/Conclusions:OVDs with only Hyaluronic Acid as Polysaccharide

10. Discussion/Conclusions:OVDs with both Hyaluronic Acid and Chondroitin Sulfate