arshinoff sa ic antibiotics, isbcs,xylo-phe,tsst...

Arshinoff SA IC Antibiotics, ISBCS,XYLO-PHE,TSST ASCRS 2016 Myers Chemicals Course p 1

SA Research

Be#er Surgery Through Chemicals IC Prophylaxis, ISBCS, (IC XYLO-‐PHE), OVDs & TSST.

ASCRS 2016 New Orleans May 8, 2016

Sunday 1-2:30 PM, Rm. 235-6

Steve A. Arshinoff MD FRCSC Eye Associates, Humber River Hospital University of Toronto, Toronto, ON, Canada McMaster University, Hamilton, ON, Canada

Financial Disclosures: Alcon Laboratories Inc. - C Abbott medical Optics – C Bausch & Lomb – C iMed Pharma – C Zeiss -C Rayner - C Arctic Dx. - C

OFF LABEL CONTENT

*Preop Topical G4 Fluoroquinolones achieve cidal aqueous levels at the beginning of surgry.

DRUG

Administration Tech.

Gati- aqueous conc. at surgery onset (µg/ml).

Moxi- aqueous conc. at surgery onset (µg/ml)

1 gtt QID x 2d 0.19 ± 0.23 0.38 ± 0.32

1gtt QID x 2 d + Q15min x 3 pre-op (2h)

0.82 ± 0.31 2.16 ± 1.12

1gtt qid x 4d + in wick 0.22 ± 0.07 0.88 ± 0.46

1 gtt QID x 4d + in wick + pre-op x 1

0.30 ± 0.21 0.97 ±0.63

MIC (mg/L) Endoph isolates 0.09 – 0.38 0.06 – 0.19

*Ong-Tone L. Aqueous Humour Penetration of Gatifloxacin and Moxifloxacin Eyedrops Given by Different Methods Before Cataract Surgery. J. Cataract Refract Surg. 2007. 33: 59-62.

? Disagreement with Katz & Masket. Absorption of topical Moxi.Cornea 2005;24: 955-958

SA Research

Published intracameral cephalosporin studies all show 80-‐90+% endophthalmiEs rate reducEon with use of intracameral cephalosporins.

Study IC AnJbioJc years n POE: No IC POE: IC rate p 1Garat

Barcelona, Spain Cefazolin

2.5 mg/0.1ml 2004 -‐2007 18,603 1/240 1/2,130 0.047% <0.001

2Romero Reus, Spain

Cefazolin 1mg/0.1 ml 2001 -‐2004 7,268 1/160 1/1,809 0.055% <0.001

7Garcia –Saenz Madrid, Spain

Cefuroxime 1.0 mg/0.1 ml 1999 -‐ 2008 13,652 1/169 1/2,352 0.043% <0.001

3Montan, Sweden

Cefuroxime 1mg/0.1 ml 1990 -‐ 1999 66,200 1/383 1/1,600 0.06% <0.001

4Wejde, Sweden, NCR

Cefuroxime 1mg/0.1ml. 1999 -‐ 2001 188,151 1/454 1/1,887 0.053% <0.001

5Lundström, Sweden NCR

Cefuroxime 1mg/0.1 ml 2002 –2004 225,471 1/290 1/2,231 0.045% <0.001

8Friling, Lundström Sweden NCR

Cefuroxime 1mg/0.1 ml 2005 -‐ 2010 464,996 1/255 1/3,756 0.027% <0.001

6Barry, ESCRS Study

Cefuroxime 1mg/0.1ml 2003 -‐ 2006 16,603 1/337 1/1,621 0.07% <0.001

9Shorstein, Kaiser, California

Cefuroxime 1mg/0.1ml 2007-‐2011 16,264 1/310 1/3,125 0.032% <0.001

10Arshinoff, BasJanelli. iSBCS

Cefuroxime 1mg/0.1ml 2010-‐11 69,720 1/1,987 1/9,175 0.011% <0.01

11Jabbarvand, Hashemian… Teheran

Cefuroxime 1mg/0.1ml 2006 -‐ 2014 480,112 1/4,055 0/25,920 0 <0.01

Sum Weight averaged 1990 -‐ 2014 1,567,040 1/560 1/3,322 0.031% <0.001

NCR = Swedish national cataract registry, POE = Post –Operative Endophthalmitis, IC = intracameral antibiotic

SA Research

Are other intracameral anEbioEcs beGer than cefuroxime?

•  ESCRS starEng a European EndophthalmiEs registry. �  ESCRS trying to enforce cefuroxime use across Europe

�  The ESCRS study did not compare efficacy of different IC anEbioEcs. It tested only IC cefuroxime.

�  Recent iSBCS study (internaEonal Society of Bilateral Cataract Surgeons) compared different regimens.

�  Huge numbers are needed to prove superiority of one anEbioEc over another (because of the extremely low incidence of post-‐operaEve endophthalmiEs in all groups). �  both vancomycin and moxifloxacin tended to have lower infecEon rates

than cefuroxime. SA

Research

Issues with different antibiotics 1.  Vancomycin

- does not cover gram negatives (5% infections). - generics in Canada cause TASS

- hemorrhagic occlusive retinal vasculitis (HORV) - complex dilution. - agent of last resort.

2.  Cefuroxime

- MRSA & CNS, gm-ves, enterococci not covered - Complex dilution – errors ! TASS - Fusarium contamination – 8 cases in Turkey

- Allergy, Anaphylaxis.

3.  Moxifloxacin - increasing resistance (dose dependent) - not available as single dose commercial prep. (USA, Canada, Europe).

- retinal detachment rate increased with systemic ciprofloxacin ?

- “Toxi-Moxi” – bilateral iritis & transillumination 2° syst moxi (J. Davis). - Uveitis risk with oral moxi. Eadie B, Etminan M, Mickelberg FS. JAMA Ophth online Oct. 2, 2014. doi:.10.1001/jamaophthalmol 2014.3598. Risk ratio: moxi = 2.98, cipro = 1.96.

Kron-Gray MM, Witkin AJ et al. IOVS June 2015; 56:3853. 11 eyes / 6 pts; (Michigan)

SA Research

Commercial IC cefuroxime, Nov. 2012. (not approved or available in USA or Canada)

Cefuroxime (Aprokam® )

- Laboratories Théa 28/11/2012 - 50 mg anhydrous cefuroxime - reconstituted with 5 ml. saline.

Contains 1mg. cefuroxime/0.1 ml.

Single use only BOX OF 10 VIALS WITH PATIENT FLAG LABEL


SA Research

IC moxifloxacin PFS available, Oct. 2013. (not approved or available in USA or Canada)

4 Quin PFS (prefilled syringe) Manufacturer: Contacare Ophthalmics, Gujarat, India. Marketer: Entod Pharmaceuticals Ltd., Mumbai, India. 0.5% moxifloxacin (500 mcg/0.1 cc, pH=6.7, 292 mOsm/kg) - prefilled syringe; 0.5, 1.0 ml.

- 0.1 cc injection 1.6 mg. / ml. in AC

SA Research

Does moxifloxacin have advantages over cefuroxime and vancomycin ?

1.  Readily available -‐ Vigamox®, Alcon (non-‐preserved)

2.  Uncomplicated to dilute.

-‐ Dose = 150 µgm/0.1 cc. (use 0.3 cc. è 1.5 mg/ml AC.)

-‐ Mix 3 ml Vigamox® + 7 ml BSS in 12 cc. syringe. Millipore.

3.  Dose dependent, bactericidal, broad spectrum.

*If an infecJon occurs, it will likely be moxifloxacin resistant Staph., which is very sensiJve to the usual endophthalmiJs protocol of vancomycin and

ceoazidime, while infecJons that occur with IC cefuroxime are ooen with destrucJve resistant bacteria , like enterobacter.

4.  Drug allergy very rare with moxifloxacin.

* Personal communication: Per Montan MD (presented by Anders Behndig at SOE Vienna, June 7, 2015) SA Research

Dose of Intracameral moxifloxacin Moxifloxacin Dose 100 µg in 0.1cc. 300 µg in 0.2cc 450 µg in 0.3cc 500 µg in 0.1cc

Final AC concentraEon -‐ at injecEon 330 mg / L 1000 mg / L 1500 mg / L 1660 mg / L

AC concentraEon – 1 hour 82 mg / L 250 mg / L 375 mg/L 415 mg /L

AC concentraEon – 2 hours 20 mg / L 62 mg / L 94 mg/L 104 mg /L

AC concentraEon – 3 hours 5 mg / L 16 mg / L 24 mg/L 26 mg / L

AC concentraEon – 4 hours 1 mg / L 4 mg / L 6 mg/L 6.5 mg / L

Bactericidal effect (level > 320 mg/L) 0.5 hrs 1.0 hrs 1.5 hrs 1.5 hrs

= < MIC90 most resistant case = < MIC of our case

• It is clear from the above that our previous moxifloxacin dose was likely inadequate to eradicate resistant strains of Staphylococci, despite the rapid dose dependent bactericidal effect of moxifloxacin.

• The 500 µg/0.1 cc. (direct from the bottle of eye drops) has the disadvantage of a less physiologic solution for intracameral injection compared to the 300 µg/0.2 cc, or 450 µg/0.3 cc, (mixture of 3 cc Vigamox® from the bottle diluted with 7 cc BSS).

• We have therefore chosen to use 450 µg/0.3 cc as our routine, as a compromise of bactericidal efficacy and safety for the endothelium. Simple exchange of AC volume.

= > 10x MIC90 most resistant case = < 10x MIC90 most resistant case

ISBCS & IC Antibiotics: SAA Personal History to 2016 03.

ISBCS performed routinely: 1996 01 – 2016 03 (20 yrs)

§  All cataracts 1996 01 to 2016 03 31 = 12,631 §  ISBCS Eyes = 9,894 (78.3%) §  DSBCS or UCS = 2,737 (21.7%)

§  IC Vigamox Cataracts = 7,834 (2004 12 – 2016 03) §  2004 12 è 3,430 at 100μg/0.1 cc. ! Endophth cases = 2

§  1 incision trauma 2 weeks post op

§  1 unilateral moxi resistant S. epi 2011 01

§  2010 02 ! 3,352 at 300μg/0.2 cc. ! Endophth cases = 0

§  2014 09 ! 1,052 at 450μg/0.3 cc. ! Endophth cases = 0

§  IC Vancomycin cataracts = 4,797 (1996 01 - 2004 11)

! Endophth cases = 0

§  No IC antibiotics, all UCS = ~ 6,000 (1980-1995)

! Endophth cases = 1

Advantages of ISBCS

SA Research

1. Overcomes fear for patient who had a problem with 1 eye.

2. More improvement after 2nd eye surgery than 1st.

3.  Immediate rehabilitation of visual system

4. Better planning of refractive result

- no period of anisometropia.

5.  Fewer patient visits (traffic accident deaths).

6.  Improved care by hospital staff.

7.  Unusual patients (Christopher)

The 3½ big fears with ISBCS

½. Preferred practice patterns & collegial hostility.

2.  Post operative retinal detachment (too late to matter)

3.  *IOL power errors in 1st eye, correctable for 2nd ? (resolved by IOLM & Lenstar, Haigis & Olson Eqns. & ASCRS post Refr. Surg. Calc. )

4.  Bilateral post operative endophthalmitis (BSE) & TASS (Toxic Anterior Segment Syndrome).

*Jabbour J, Irwig L, Macaskill P, et al. Intraocular lens power in bilateral cataract surgery: Whether adjusting for

error of predicted refraction in first eye improves prediction in the second eye. JCRS 2006; 32:2091-2097.

*Mamalis N. Aziz S, Cutler-Peck C, Monson B. ASCRS/ESCRS survey of foldable IOLs requiring explantation

or secondary interbvention: 2008 update. Presented at 2009 ESCRS Barcelona Sept 12, 2009. SA Research


SA Research

IC xylo-phe

1.  Add minim (0.3 cc) 10% phenylephrine to 5 cc BSS in 6 cc syringe (è 0.57%, diluted 17.7x).

2.  Add 4-5 drops of above phenylephrine solution to xylocaine (Astra 1% non-preserved insotonic xylo polyamp) on scrub tray (è0.08%, diluted ≥200x).

3.  Inject 0.1 cc IC xylo-phe thru side port. (1.) �  Almost all pupils dilate to 8-9 mm in 10 seconds.

4.  Inject 0.1 cc IC xylo-phe under OVD. (2.) �  1 more mm of pupil dilation.

IC xylo-phe IC xylo-phe

10 sec.

Alternatives available in Europe (1 ml glass vials – single use) Phenocaine injection (Entod, UK), Nov. 2016 Mydrane (Thea)

Mydrane Xylo-Phe Phenocaine Tropicamide 0.02% − − Phenylephrine HCl 0.31% 0.08% 0.1% Lidocaine 1% 1% 1%

SA Research

If you would like this

xylo-phe formulation

& use sheet,

please email me at:

[email protected]

SA Research

OVDs: TSST Arshinoff SA, Norman R. JCRS 2013; 39:

1196-1203.

The Tri-Soft Shell

Technique (TSST)

is a logical system of

unification of all

previous soft shell

techniques to make

them all easier to

understand & perform.

SA Research

Pre Capsulorhexis Step

ULTIMATE SOFT SHELL TECHNIQUE (USST)*

Pre IOL Implantation Step

*Arshinoff Steve A. Using BSS with viscoadaptives in the ultimate soft-shell technique. J Cataract Refract Surg. 2002 Sep;28(9):1509-14.


SA Research

TRISOFT SHELL TECHNIQUE (TSST):

Enhanced by adding BSS below the cohesive OVD

Capsulorhexis is easier when BSS is injected

onto the capsule surface, after OVD

injection, when using Soft Shell Technique,

or any viscous cohesive OVD alone.

Dispersive OVD Cohesive OVD

BSS

SA Research

Tri-Soft Shell Technique (TSST)

Arshinoff Steve. Cataract Surgery Compromised Endothelium. In Chakrabarti A. Cataract Surgery in Diseased Eyes. Jaypee Brothers Ltd., New Delhi. 2013. SA

Research

1. Dispersive filled space (injected 1st)

2. Viscoadaptive filled space (injected 2nd)

3. BSS filled space (injected 3rd)

Incision

1.  Low flow → low turbulence (Ozil).

1.  Asp flow rate ~ 15-‐25 cc/min.

2.  Vacuum < 250 mm Hg.

3.  BoGle height ~ 75 cm

2.  Reinject OVDs as needed (H5):

-‐ e.g. aner hydrodissecEon.

3.  Keep phaco & I/A Eps deep to ‘rhexis, leave dispersive at end.

TSST for Fuchs’ & Low ECC

SA Research

TSST è * IFIS Soft Shell Bridge

*Arshinoff Steve A. Modified SST-USST for tamsulosin-associated intraocular floppy-iris syndrome. JCRS 2006; 32: 559-561. April.

è

Arshinoff SA, Modabber M. Cataract Surgery in Intraoperative Floppy Iris Syndrome (IFIS) Eyes. In Chakrabarti A. Cataract Surgery in Diseased Eyes. Jaypee Brothers Ltd., New Delhi. 2013.

Arshinoff Steve. Cataract Surgery in Compromised Endothelium. In Chakrabarti A. Cataract Surgery in Diseased Eyes. Jaypee Brothers Ltd., New Delhi. 2013.

3. Xylo-Phe filled space (injected 3rd

Simple Summary: use OVDs & stretch pupil

SA Research

Soft Shell Techniques - Summary

Tri-Soft Shell Technique (TSST)

SA Research

Conclusions: IC AnJbioJcs, ISBCS, (XYLO-‐PHE), TSST.

1.  All studies, irrespective of background infection rate, demonstrate 80+% reduction in endophthalmitis with IC antibiotics. Moxifloxacin appears to be best @ 300 µg/0.2 cc, (diluted 3:7 with bss).

2.  ISBCS is better.

3.  XYLO-PHE makes surgery much easier.

4.  TSST with variations, permits simpler surgery for the vast majority of cases.

STEVE A. ARSHINOFF MD FRCSC

[email protected]

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arshinoff sa ic antibiotics, isbcs,xylo-phe,tsst...

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