Free Radical Generation Free Radical Generation During Phacoemulsification Using During Phacoemulsification Using

Different ConsolesDifferent Consoles

Professor Steven D. Aust, PhD, Professor Steven D. Aust, PhD, Thomas Hebdon, Jordan Humbert, Thomas Hebdon, Jordan Humbert,

Scott Terry, Broc GundersenScott Terry, Broc Gundersen

Research funded and travel expenses reimbursed by Alcon LaboratoriesResearch funded and travel expenses reimbursed by Alcon LaboratoriesNo financial interest in the products discussedNo financial interest in the products discussed

ASCRS 2009ASCRS 2009April 3-8, San Francisco, CAApril 3-8, San Francisco, CA

Department of Chemistry and BiochemistryDepartment of Chemistry and BiochemistryUtah State University Utah State University

Logan, Utah USALogan, Utah USA

Study PurposeStudy Purpose

To quantitate hydroxyl radicals produced during phacoemulsification using various power modulations and ultrasonic modalities on two phacoemulsification platforms.

The hydroxyl radical is a highly reactive free radical molecule that potentially creates oxidative stress in an ocular environment.

Background Background StudiesStudies

References on free radical effects during phacoemulsification: Geffen N, Topaz M, Kredy-Farhan L, Barequet I, Farzam N, Assia E,

Savion N. Phacoemulsification-induced injury in corneal endothelial cells mediated by apoptosis: In vitro model. J Cataract Refract Surg 2008; 34:2146-2152.

Takahashi H, Sakamoto A, Takahashi R, Ohmura T, Shimmura S, Ohara K. Free radicals in phacoemulsification and aspiration procedures, Arch Ophthalmol 2002; 120:1348-1352.

Previous Work: Cameron M, Poyer J, Aust S. The identification of free radicals

produced during phacoemulsification. J Cataract Refract Surg 2001; 3:463-470

Aust S, Gardner J, Humbert J, Dimalanta R. Free radical generation as affected by different phacoemulsification technologies. Presented at: American Academy of Ophthalmology, November 9, 2008. Atlanta, GA.

Materials and ProcedureMaterials and Procedure

Experiments were performed using two phacoemulsifier consoles: Alcon Infiniti Vision System Advanced Medical Optics (AMO, now Abbott)

Sovereign Compact System All used their associated handpieces and tips The consoles and handpieces were operated

between 0 and 100% power in 10% increments BSS flowing with continuous irrigation/aspiration

at 28mL/min was sonicated, and aspirate was collected

Chemical MethodologyChemical Methodology

Hydroxyl radical concentrations were estimated using the deoxyribose method with 5mM deoxyribose added to the irrigation solution (BSS)

The concentration of malondialdehyde (MDA) in the aspirated irrigation solution was measured as a correlate to hydroxyl radical concentration

Reference on methodology: Halliwell, B. and Gutteridge JMC. Hydroxyl Radicals Assayed by Aromatic

Hydroxylation and Deoxyribose Degradation, Handbooks of Methods for Oxygen Radical Research (1985); 177-180, Greenwald R., CRC Press, Boca Raton Florida, 1985.

Experimental Set-upExperimental Set-up

Peristaltic Pump

Ultrasonic Tip

BSS fluid containing 5mM deoxyribose flows from the irrigation bottle to the phacoemulsification handpiece where it is sonicated in a reaction vessel. On the Infiniti Vision System, the solution is aspirated with the system’s peristaltic pump from the reaction vessel and collected in the drain bag where a sample port has been added in the bottom of the bag to allow samples to be chronologically collected as it flows. The same is executed with the Sovereign Compact System, but solution is aspirated from the reaction vessel and collected from the tube exiting the peristaltic pump prior to the drain bag (not shown).

Deoxyribose

Malondialdehyde

Cheeseman KH, Beavis A, Esterbauer H. Hydroxyl-radical-induced iron catalyzed degradation of 2-deoxyribose. Biochem J. 1988; 252:659-653.

Degradation of Deoxyribose by the Hydroxyl Degradation of Deoxyribose by the Hydroxyl Radical to form MalondialdehydeRadical to form Malondialdehyde

Abstraction of a hydrogen atom from C4 of deoxyribose results in the formation of malondialdehyde (second compound after reaction 6)

Testing Configurations Studied Testing Configurations Studied Among Various Platforms, Among Various Platforms,

Power Modulations, and ModalitiesPower Modulations, and Modalities

Continuous Longitudinal Ultrasound1. Infiniti Continuous

0.9 mm 30° Round Tip2. Sovereign Compact Continuous

20 Gauge 30° LAMINAR® Flow Phaco Tip Pulse-Modulated Longitudinal Ultrasound

Using same tips as above for each platform and all at 33% duty cycle3. Infiniti Pulse Mode

6msec on, 12msec off4. Sovereign Compact WhiteStar C/F (6msec on, 12msec off) Mode5. Sovereign Compact WhiteStar C/F Mode with ICE (20% initial

“punch”) Continuous Torsional Ultrasound

6. Infiniti Torsional 0.9mm 45° Kelman® Mini Flared ABS® Tip

Power Modulation and Modality Comparisons of Hydroxyl Radical (MDA) Production

0

5

10

15

20

25

30

35

40

45

50

0 10 20 30 40 50 60 70 80 90 100

% Phaco Power

[MD

A] (m

M)

Sovereign Compact Continuous Long. (20 Gauge 30° LAMINAR® Flow Phaco Tip)

Infiniti Continuous Longitudinal (0.9 mm 30° Round Tip)

Sovereign Compact Long WhiteStar C/Fwith ICE (20 Gauge 30° LAMINAR® Flow Phaco Tip)(6msec on, 12msec off, 33% duty cycle)Sovereign Compact Long. WhiteStar C/F (20 Gauge 30° LAMINAR® Flow Phaco Tip)(6msec on, 12msec off, 33% duty cycle)

Infiniti Pulse Mode (0.9 mm 30° Round Tip) (6msec on, 12msec off; 33% duty cycle)

Infiniti Torsional Continuous (0.9mm 45° Kelman® Mini Flared ABS®Tip)

ConclusionConclusion

Continuous Longitudinal Ultrasound On either platform using similar tip

designs, continuous modes produced the highest concentrations of MDA Peak concentrations were about 40nM MDA

at 90% power Between these two tests, higher

concentrations were measured with Sovereign Compact at low power (<70%)

ConclusionConclusion

Pulse Modulated Power Equivalent pulse modulation testing (about 33% duty-

cycle) on either platform also gave similar results to each other and expectedly lower MDA concentrations compared to continuous U/S Sovereign Compact delivered higher concentrations at low

power (<50%)

Sovereign Compact W/S with ICE produced noticeably more MDA than without, likely because of the initial “punch” of power administered at each pulse

ConclusionConclusion

Continuous Torsional Modality With its distinctly different motion as compared

to traditional, longitudinal ultrasound, along with its design-specific tip, continuous torsional ultrasound produced the least amount of MDA among all other modes compared

All data comparisons made are statistically significantly different (p<0.05 or better; data on file)