““A Comparison of Wound Strength with and without A Comparison of Wound Strength with and without Hydrogel Liquid Ocular Bandage in Human Cadaver Eyes”Hydrogel Liquid Ocular Bandage in Human Cadaver Eyes”

This study was supported in part by an unrestricted grant from Becton, Dickinson and Company, Waltham, MA, USA; and by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY, to the Department of Ophthalmology & Visual Sciences, University of Utah. Dr. Olson is a consultant to Becton, Dickinson and Company.

Surekha Maddula, M.D., Don K. Davis, M.D., Peter J. Ness, M.D., Randall J. Olson, M.D.

Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah

IntroductionIntroduction The advancements in microsurgery and The advancements in microsurgery and

disadvantages of sutures has shifted toward disadvantages of sutures has shifted toward sutureless surgery in clear corneal incisions and sutureless surgery in clear corneal incisions and pars plana vitrectomy procedurespars plana vitrectomy procedures

However, sutureless incisions are more likely However, sutureless incisions are more likely than sutured incisions to leak after surgery, and than sutured incisions to leak after surgery, and a leaky wound is a potential source for bacterial a leaky wound is a potential source for bacterial endophthalmitisendophthalmitis1,21,2

Studies show that post operative leaking and Studies show that post operative leaking and sutureless surgery is associated with sutureless surgery is associated with endophthalmitis due to ingress and egress of endophthalmitis due to ingress and egress of ocular fluids from changing ocular pressureocular fluids from changing ocular pressure2-5 2-5

Introduction Adhesive sealants on corneal or scleral wounds

may be a solution to early post-operative incision leakage

Polyethylene glycol (PEG) hydrogels are synthetic materials that may have advantages over biological materials.

Hydrogel liquid ocular bandages are safe Comfortable Easy and quick to apply Persist on for several days Protect the wound Enhance wound strength

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ObjectiveObjective

The purpose of this study is to The purpose of this study is to determine whether a hydrogel determine whether a hydrogel liquid ocular bandage is liquid ocular bandage is efficacious in improving wound efficacious in improving wound strength. strength.

Materials and MethodsMaterials and Methods 5 cadaver eyes were obtained from Lions Eye Bank to test a total of 5 cadaver eyes were obtained from Lions Eye Bank to test a total of

20 23-gauge incisions and 20 clear corneal incisions20 23-gauge incisions and 20 clear corneal incisions In each eye a 23-gauge pars plana vitrectomy with Alcon Infinity was In each eye a 23-gauge pars plana vitrectomy with Alcon Infinity was

performed to remove vitreous that may potentially block incisionsperformed to remove vitreous that may potentially block incisions Pars plana incisions were created with 23-gauge MVR blades then Pars plana incisions were created with 23-gauge MVR blades then

tested for wound bursting strength by increasing bottle height of BSS tested for wound bursting strength by increasing bottle height of BSS connected to the optic nerve via 23-gauge needle. connected to the optic nerve via 23-gauge needle.

Each incision was tested with and without hydrogel liquid bandage, Each incision was tested with and without hydrogel liquid bandage, Ocuseal and then sealed with cyanoacrylate for a total of 4 pars plana Ocuseal and then sealed with cyanoacrylate for a total of 4 pars plana incisions in each eyeincisions in each eye

A clear corneal incision was then made with a 2.8mm angled steel A clear corneal incision was then made with a 2.8mm angled steel blade and the iris was removed, lens dislocated posteriorly and blade and the iris was removed, lens dislocated posteriorly and needle in optic nerve advanced into the anterior chamberneedle in optic nerve advanced into the anterior chamber

Each clear corneal incision was then tested with and without Ocuseal Each clear corneal incision was then tested with and without Ocuseal and then sealed with cyanoacrylate for a total of 4 clear corneal and then sealed with cyanoacrylate for a total of 4 clear corneal incisions in each eyeincisions in each eye

  23 Gauge Incisions Clear Corneal Incisions

 Bursting Pressure w/o ocuseal (mmHg)

Bursting Pressure with ocuseal (mmHg)

Bursting Pressure w/o ocuseal (mmHg)

Bursting Pressure with ocuseal(mmHg)

Cadaver Eye #1        

Incision #1 18.6 246.2 (no burst) 37.2 100.7

Incision #2 14.9 246.2 (no burst) 44.7 110

Incision #3 35.4 212.6 35.4 89.5

Incision #4 44.7 210.7 18.6 96.9

Cadaver Eye #2        

Incision #1 87.7 246.2 (no burst) 93.2 169.7

Incision #2 44.8 246.2 (no burst) 67.1 175.3

Incision #3 55.9 246.2 (no burst) 70.9 246.2 (no burst)

Incision #4 50.4 246.2 (no burst) 95.1 194

Cadaver Eye #3        

Incision #1 65.3 179 41 233.1

Incision #2 76.5 167.8 55.9 195.8

Incision #3 70.9 158.52 52.1 246.2 (no burst)

Incision #4 76.5 160.4 44.7 246.2 (no burst)

Cadaver Eye #4        

Incision #1 57.8 231.3 67.1 246.2 (no burst)

Incision #2 37.3 18.6 52.2 246.2 (no burst)

Incision #3 46.6 235 52.2 171.6

Incision #4 69 246.2 (no burst) 67.1 214.5

Cadaver Eye #5        

Incision #1 28 190.2 57.8 240.6

Incision #2 26.1 186.5 102.6 246.2 (no burst)

Incision #3 26.1 246.2 (no burst) 67.1 246.2 (no burst)

Incision #4 26.1 91.4 67.1 246.2 (no burst)

Results

ResultsResults

Mean Leakage pressure was determined and compared using a student T-test.

For non-parametric testing a Chi-square analysis was used.

With four comparisons, significance with a Bonferroni correction for multiple comparisons was set at P<.012

ResultsResults2.8 mm Corneal Incisions 23-Gauge Scleral Incisions

Mean Leakage without liquid ocular bandage 59.5 +/-21.0mmHg 47.9+/-21.4mmHg

Mean Leakage with liquid ocular bandage 198.1+/-57.6mmHg 200.6+/-60.4mmHg

P value for above two comparisons P<.0001 P < .0001

Number of Incisions without leakage at maximal pressure without bandage

0 out of 20 0 out of 20

Number of Incisions without leakage at maximal pressure with bandage

8 out of 20 7 out of 20

P value for above two comparisons P = .009

Table. Intraocular pressure at which incision leakage was noted for both 23-gauge scleral and 2.8 mm limbal incisions in human cadaver eyes, both with and without use of a hydrogel liquid bandage formulated for ocular use. Our maximal attainable intraocular pressure was 246mmHg, the figure which we used when the incision did not leak at this pressure. We also compare the number of incisions that did not leak at our maximal attainable pressure of 246mmHg.

Discussion The goal of an ocular bandage is to protect injured tissue, and to help the

reemergence of a normal anatomic and functional state of the ocular incision through wound remodeling and repair.

Advantages to synthetic hydrogel sealants over fibrin and cyanoacrylate alternatives:

Quick and easy to prepare and use Can be applied at neutral pH1

Require no external energy source Safe and tolerable in the eye, non-toxic and no antigenicity or immune

response6

85% water content after application; has physical properties comparable to tissue, and suitable to fill in irregularities and conform to the normal architecture

Polymerization after application takes approximately 45 seconds to achieve maximal strength Watertight and flexible that cornea can resist egress and ingress of ocular surface contaminants by 92% over incisions without such a bandage7

Removal is not an issue as it breaks down under physiological conditions and degradation products are water soluble and cleared through body

Conclusions Postoperative hypotony and fluctuations in intraocular pressure secondary

to incision leakage is a concern8-10 Pressure changes in the eye are consequences of a faulty incision and can

cause egress of the contaminated tear film into the eye, potentially leading to endophthalmitis

A hydrogel liquid bandage has the potential advantage of easy and quick application, is well tolerated, and resists incision distortion due to its malleable nature

Our results showed that the hydrophilic acrylic hydrogel PEG bandage is statistically significant for resistance to wound leakage at very high intraocular pressures for both 2.8mm corneal incisions and 23-gauge scleral incisions.

Application of hydrogel liquid ocular bandage allows for substantially higher intraocular pressures before leakage when compared to the native wound and we suggest its use in the early postoperative period for procedures using sutureless incisions.

ReferencesReferences 1.1. Grinstaff MW. Designing hydrogel adhesives for corneal wound repair. Grinstaff MW. Designing hydrogel adhesives for corneal wound repair.

Biomaterials 2007; 28:5205-5214Biomaterials 2007; 28:5205-5214 2.2. Nagaki Y, Hayasaka S, Kadoi C, Matsumoto M, Yanagisawa S, Watanabe K, et Nagaki Y, Hayasaka S, Kadoi C, Matsumoto M, Yanagisawa S, Watanabe K, et

al. Bacterial endophthalmitis after small-incision cataract surgery. effect of incision al. Bacterial endophthalmitis after small-incision cataract surgery. effect of incision placement and intraocular lens type. J Cataract Refract Surg 2003; 29:20-26placement and intraocular lens type. J Cataract Refract Surg 2003; 29:20-26

3.3. Results of the Endophthalmitis Vitrectomy Study. A randomized trial of Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Endophthalmitis Vitrectomy Study Group. Arch Ophthalmol bacterial endophthalmitis. Endophthalmitis Vitrectomy Study Group. Arch Ophthalmol 1995; 113:1479-14961995; 113:1479-1496

4.4. Wallin T, Parker J, Jin Y, Kefalopoulos G, Olson RJ. Cohort study of 27 cases Wallin T, Parker J, Jin Y, Kefalopoulos G, Olson RJ. Cohort study of 27 cases of endophthalmitis at a single institution. J Cataract Refract Surg 2005; 31:735-741of endophthalmitis at a single institution. J Cataract Refract Surg 2005; 31:735-741

5.5. Kunimoto DY, Kaiser RS. Incidence of endophthalmitis after 20- and 25-gauge Kunimoto DY, Kaiser RS. Incidence of endophthalmitis after 20- and 25-gauge vitrectomy. Ophthalmology 2007; 114:2133-2137vitrectomy. Ophthalmology 2007; 114:2133-2137

6.6. Kim T, Kharod BV. Tissue adhesives in corneal cataract incisions. Curr Opin Kim T, Kharod BV. Tissue adhesives in corneal cataract incisions. Curr Opin Ophthalmol 2007; 18:39-43Ophthalmol 2007; 18:39-43

7.7. Hovanesian JA. Cataract wound closure with a polymerizing liquid hydrogel Hovanesian JA. Cataract wound closure with a polymerizing liquid hydrogel ocular bandage. J Cataract Refract Surg 2009; 35:912-916ocular bandage. J Cataract Refract Surg 2009; 35:912-916

8.8. Irak-Dersu I, Nilson C, Zabriskie N, Durcan J, Spencer HJ, Crandall A. Irak-Dersu I, Nilson C, Zabriskie N, Durcan J, Spencer HJ, Crandall A. Intraocular pressure change after temporal clear corneal phacoemulsification in normal Intraocular pressure change after temporal clear corneal phacoemulsification in normal eyes. Acta Ophthalmol 2009 [Epub ahead of print]eyes. Acta Ophthalmol 2009 [Epub ahead of print]

9.9. Schwenn O, Dick HB, Krummenauer F, Krist R, Pfeiffer N. Intraocular pressure Schwenn O, Dick HB, Krummenauer F, Krist R, Pfeiffer N. Intraocular pressure after small incision cataract surgery: temporal sclerocorneal versus clear corneal incision. after small incision cataract surgery: temporal sclerocorneal versus clear corneal incision. J Cataract Refract Surg 2001; 27:421-425J Cataract Refract Surg 2001; 27:421-425

10.10. Gupta OP, Ho AC, Kaiser PK, Regillo CD, Chen S, Dyer DS, et al. Short-term Gupta OP, Ho AC, Kaiser PK, Regillo CD, Chen S, Dyer DS, et al. Short-term outcomes of 23-gauge pars plana vitrectomy. Am J Ophthalmol 2008; 146:193-197outcomes of 23-gauge pars plana vitrectomy. Am J Ophthalmol 2008; 146:193-197