Rheologic Characterization of Ophthalmic Viscosurgical

Report
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).
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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
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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
OVD 
vacuum is applied,
using the automated model
as described in the referenced article.1
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
pipette
tip
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Materials: OVDs Evaluated
Polysaccharide Content
OVD
Manufacturer
%
MW, kDa
%
MW, Da
Total Polysaccharide,
%
Viscoat® OVD
Alcon
(USA)
3%
500
4%
22,500
7%
DisCoVisc®
OVD
Alcon
(USA)
1.65%
1700
4%
22,500
5.65%
Ixium® HCS
OVD
LCA Pharmaceutical
(France)
2%
2400
2%
50,000
4%
Vitrax® OVD
AMO
(USA)
3%
645
--
--
3%
Opegan® Hi
OVD
Santen
(Japan)
1%
2000
--
--
1%
Healon® OVD
AMO
(USA)
1%
4000
--
--
1%
Hyaluronic Acid
Chondroitin Sulfate
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.
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Results: Cohesion–Dispersion Index
 100 = max
cohesive
100
Cohesion – Dispersion Index
(% OVD aspirated / 100 mm Hg)
90
80
70
60
60
50
40
32
30
21.3
20
10
12
2.8
3.4
0
VITRAX®
OVD
VISCOAT® DISCOVISC® IXIUM®
OVD
OVD
HCS OVD
More Dispersive
 0 = max
dispersive
HEALON® OPEGAN HI®
OVD
OVD
More Cohesive
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Results: Zero-Shear Viscosity
500,000
450,000
426,000
Viscosity (mPa.s)
400,000
350,000
300,000
240,000
250,000
250,000
200,000
150,000
100,000
50,000
45,000
50,000
50,000
VITRAX®
OVD
VISCOAT®
OVD
IXIUM®
HCS OVD
0
Less Viscous
HEALON®
OVD
DISCOVISC® OPEGAN HI®
OVD
OVD
More Viscous
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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):
↓
Less
viscous
(more
thinning)
↓
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.

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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 lowermolecular-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-molecularweight OVDs, to
Low CDI value indicates high retention despite fluid
turbulence, but difficult removal during irrigation/aspiration.
• 32% - 60% for highermolecular-weight OVDs
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.
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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.
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