Masoud Jafari, PharmD, PhD Rheologic Characterization of Ophthalmic Viscosurgical Devices Containing Sodium Hyaluronate and Sodium Chondroitin Sulfate 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 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.

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. Objective The 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).

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

Methods II Cohesion/Dispersion Evaluation: OVDs were evaluated in terms of the Cohesion-Dispersion Index, which is A value between 0 (very dispersive) and 100 (very cohesive) Reported as the % OVD aspirated / 100 mm Hg Derived by testing how much of a 0.5-ml sample of OVD is aspirated into a pipette tip when a given amount of vacuum is applied, using the automated model as 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

Materials: OVDs Evaluated Manufacturer Polysaccharide Content Hyaluronic Acid Chondroitin Sulfate Total Poly-saccharide, % % MW, kDa MW, Da Viscoat® OVD Alcon (USA) 3% 500 4% 22,500 7% DisCoVisc® OVD 1.65% 1700 5.65% Ixium® HCS OVD LCA Pharmaceutical (France) 2% 2400 50,000 Vitrax® OVD AMO (USA) 645 -- Opegan® Hi OVD Santen (Japan) 1% 2000 Healon® OVD 4000 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 (AkAkin Ilac San) were not available to us in the US.

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

Results: Zero-Shear Viscosity Less Viscous More Viscous

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. ↓ Less viscous (more thinning) ↓ Ixium® HCS

Clinical Implications Discussion/Conclusions: OVDs with only Hyaluronic Acid as Polysaccharide Study Results: OVDs with only hyaluronic acid as polysaccharide exhibited… Clinical Implications … zero-shear viscosities from 45,000 Pa.s for lower-molecular-weight OVDs, to 240,000 to 426,000 Pa.s for higher-molecular-weight OVDs These high zero-shear viscosities are best to create and maintain space maintenance during surgery in the absence of high fluid turbulence. …Cohesion-Dispersion Indices (CDIs), in units of % aspirated / 100 mm Hg, ranging from 2.8% for lower-molecular-weight OVDs, to 32% - 60% for higher-molecular-weight OVDs Low CDI value indicates high retention despite fluid turbulence, but difficult removal during irrigation/aspiration. High CDI values indicate that the OVDs stay together when pulled and so are easily aspirated at the end of surgery, but perhaps also during turbulent phases of phaco.

Clinical Implications Discussion/Conclusions: OVDs with both Hyaluronic Acid and Chondroitin Sulfate Study Results: OVDs with both hyaluronic acid and chondroitin sulfate exhibited.. Clinical Implications … zero-shear viscosities from 50,000 to 250,000 mPa.s These OVDs are available with a wide range of initial space-maintaining properties. …Cohesion-Dispersion Indices (CDIs) ranging from 3.4% to 21% aspirated per 100 mm Hg Low CDIs correlate to more dispersive characteristics, with longer retention in the anterior chamber of the eye during turbulent phases of surgery, and easier breakup of OVDs when pulled – more difficult removal at the end of surgery.