USE OF USE OF HYALURONIDASE HYALURONIDASE

ENZYME IN ENZYME IN TOPICAL TOPICAL

ANAESTHESIAANAESTHESIAGianluca Rubiolini M.D. Gianluca Rubiolini M.D.

ITALYITALY

FINANCIAL DISCLOSURE FINANCIAL DISCLOSURE The Author has no financial The Author has no financial interest in the companies interest in the companies that develop, produce and that develop, produce and

supply those drugs supply those drugs

Cararact surgery is the most common surgical procedure in ophthalmology

An increasing number of procedures is performed with topical anaesthesia in 2006 ( 61% U.S. 40% EU

).Trends in topical anaesthesia: customizing or

standardizing?

OUR GOALOUR GOAL OUR OUR KNOWLEDGEKNOWLEDGE

None of these drugs were ever used for topical anaesthesia.Hyaluronidase enzyme should not be directly apply onto the cornea. UNAPPROVED USERopivacaine was never tested for topical use. OFF LABEL USE

STANDARDIZE OUR “CUSTOM” TOPICAL ANAESTHESIA: we found a positive increase in efficacy and duration adding Hyaluronidase enzyme to Ropivacaine .

MATERIALS AND MATERIALS AND METHODSMETHODS

208 patients (Group A) 208 patients (Group A) Ropivacaine 7,5% + Ropivacaine 7,5% + Hyaluronidase enzime 30 U.I.Hyaluronidase enzime 30 U.I.

202 patients (Group B) 202 patients (Group B) Ropivacaine 10% + Ropivacaine 10% + Hyaluronidase enzime 45 U.IHyaluronidase enzime 45 U.I

101 patients (Group C) 101 patients (Group C) Ropivacaine 7,5% ( control Ropivacaine 7,5% ( control group)group)

108 patients (Group D) 108 patients (Group D) Ropivacaine 10% control group)Ropivacaine 10% control group)

None of those groups had supplementary intracameralNone of those groups had supplementary intracamerallidocaine as default. lidocaine as default.

Some patients (165) had bilateral (non simultaneus) procedure . Some patients (165) had bilateral (non simultaneus) procedure . They were always tested with the same anaesthesia. They were always tested with the same anaesthesia.

Surgical procedures:Surgical procedures: all performed by the same surgeon: facochop + iol all performed by the same surgeon: facochop + iol (Eyecryl 4x4 600, Biotech Vision Care )(Eyecryl 4x4 600, Biotech Vision Care )

Surgical time:Surgical time: from 6 minutes to 15 minutes. from 6 minutes to 15 minutes. PCO rate:PCO rate: similar in all four groups ( min. 7% max 10%) 24 similar in all four groups ( min. 7% max 10%) 24

monthsmonthsfollow up.follow up.

Technical aspects and Technical aspects and education for anaesthetic education for anaesthetic

mix preparationmix preparation

Preop & postop dataPreop & postop data Corneal Pachimetry:Corneal Pachimetry:

All 619 patients had 6 & 24 All 619 patients had 6 & 24 months post within 25months post within 25±± micron from preop. valuemicron from preop. value

Anterior segment :Anterior segment :All 619 had no changes All 619 had no changes concerning morphology concerning morphology and functions of cornea and functions of cornea iris/pupil and anterior iris/pupil and anterior sclera, IOP at 24 months sclera, IOP at 24 months post. op. post. op.

No cases of endophthalmitis No cases of endophthalmitis or non septic uveitis or non septic uveitis (TASS)(TASS)

Endothelial cells count, Endothelial cells count, 6 months post.op.:6 months post.op.:

594/619 patients had 594/619 patients had endothelial cell decrease endothelial cell decrease within 12% from preop. within 12% from preop. count.count.

25 patients were not 25 patients were not included because of the included because of the cataract ( very hard cataract ( very hard /ambroid).They had more /ambroid).They had more than 12% endothelial cell than 12% endothelial cell density decrease.density decrease.

Patient post op Patient post op questionnairequestionnaire

QUESTIONQUESTION

Did you feel Did you feel any any discomfort discomfort /pain during /pain during the surgical the surgical procedureprocedure

(multiple (multiple choice)choice)

22 I felt light discomfort because of I felt light discomfort because of

the lights/ touching sensation: no pain.the lights/ touching sensation: no pain.

3 3 I had a lot of discomfort and sometimes I had a lot of discomfort and sometimes pain: I couldn’t look at the lights.pain: I couldn’t look at the lights.

1 1 No pain /discomfort : I could No pain /discomfort : I could see lightssee lights

4 I had sharp pain : it was a terrible experience. Maybe the anaesthesia didn’t work on me .

PATIENT FEEDBACKPATIENT FEEDBACK

106

63

30

9

92

62

34

14

37

182521

40

16

3121

A GROUP B GROUP C GROUP D GROUP

1 2 3 41: NO PAIN 2: LIGHT DISCOMFORT3 DISCOMFORT AND SOME PAIN

4:SHARP PAIN

PATIENT FEEDBACKPATIENT FEEDBACK

51% 45,50%

36,60%

37,00%

A B C D

81,40%

76,20%

54,40%

51,80%

A B C D

4,30% 6,90%

20,70%

19,40%

A B C D

18,75% 23,76%45,50% 48,10%

A B C D

PATIENTS WITH NO DISCOMFORTANSWER 1

PATIENTS WITH NO OR LIGHT DISCOMFORT : ANSWERS 1 + 2

PATIENTS WITH SEVERE PAINANSWER 4

PATIENTS WITH DISCOMFORT/PAIN: ANSWERS 3 + 4

CRITICAL ANALYSIS CRITICAL ANALYSIS Patients pain classification is not objective.Patients pain classification is not objective. It depends from several subjective factors.It depends from several subjective factors.

Two answers, no pain and terrible pain , Two answers, no pain and terrible pain , can be considered relatively reliables.can be considered relatively reliables.

Patient preop. preparation and verbal Patient preop. preparation and verbal comunication with surgical staff were comunication with surgical staff were standardized as much as possible. Anyway standardized as much as possible. Anyway some variables cannot be excluded some variables cannot be excluded

Results Results In groups A and B there were more patients with In groups A and B there were more patients with

no discomfort ( answer 1 ) comparing groups C no discomfort ( answer 1 ) comparing groups C and D, from and D, from 8,9% 8,9% to to 14.4% .14.4% .

Considering answers 1+2 ( no or light dicomfort) Considering answers 1+2 ( no or light dicomfort) the difference between groups A-B and control the difference between groups A-B and control groups C-D is more evident : from groups C-D is more evident : from 21.8% 21.8% to to 29,6%29,6%

Considering answers n° 4 ( terrible/ sharp pain), Considering answers n° 4 ( terrible/ sharp pain), there was a difference between groups A-B and C-there was a difference between groups A-B and C-D from D from 12,5% 12,5% to to 16,4% 16,4% increasing, increasing, if we consider if we consider both answers 3 and 4 (severe discomfort and both answers 3 and 4 (severe discomfort and pain), from pain), from 21,74% 21,74% to to 29,35%29,35%

CONCLUSIONSCONCLUSIONS

Severe discomfort and pain during topical cataract Severe discomfort and pain during topical cataract surgery can be reduce up 29,35% of the cases surgery can be reduce up 29,35% of the cases using Hyaluronidase enzyme added to Ropivacaine using Hyaluronidase enzyme added to Ropivacaine anaesthetic for topical use with no side effects with anaesthetic for topical use with no side effects with 24 months follow up.24 months follow up.

Furthermore we found 14,4% more patients with no Furthermore we found 14,4% more patients with no discomfort during surgery just with this topical discomfort during surgery just with this topical anaesthesia without supplementary intracameral anaesthesia without supplementary intracameral lidocaine. lidocaine.

A multicenter clinical trial is actually investigating A multicenter clinical trial is actually investigating on long term follow up and time related on long term follow up and time related anaesthetic action .anaesthetic action .