FEMTOSECOND LASER CATARACT SURGERY

1. FEMTOSECOND LASER CATARACT SURGERY Revolution, Evolution, or No Solution? Making Sense of the Literature Ken Lipstock, M.D. Richmond, Virginia

2. F • emtosecond laser provides an ultrafast burst of energy. • Argon, excimer, and Nd: YAG lasers: nanosecond (10 ) pulses • Femtosecond: 10 second • Excimer: “photoablates” • Argon: “photocoagulates” • Nd: YAG and Femtosecond: “photodisrupt”. Their light energy can be absorbed by optically clear tissue and create “microcavitation bubbles” that cause an acoustic shock wave that incises the target tissue. -9 -15

3. Femtosecond laser’s ultrafast pulse allows smaller amounts of energy to provide similar power output to the NdYag. This results in much smaller cavitation bubbles therefore reduced “collateral damage” to adjacent tissues.

4. Femtosecond laser first FDA approved for LASIK flaps in 2001 and then approved for cataract surgery in 2010. • With guidance systems (OCT or Scheimpflug-like technology) it is used to make: •  Cataract clear corneal incisions and limbal relaxing incisions •  Capsulorhexis • Lens fragmentation/softening; a pretreatment prior to • phacoemulcification and/or irrigation/aspiration.

5. Mistrust but Verify We are witnessing one of the most intense marketing campaigns ever in Ophthalmology. • “It has automated, computer-guided laser precision with minimal collateral tissue damage......with emerging evidence of ......greater precision and accuracy of the anterior capsulotomy, and more stable and predictable positioning of the intraocular lens.” And this is a sentence from a scientific study in a respected peer reviewed journal! Is Femtolaser Cataract Surgery “the most important evolution since the transition to phacoemulsification?” Much has been claimed but how much is substantiated? In the following presentation I will review the literature to try to shed some light on the subject. Since the vast majority of journal articles are written by those with financial ties to the femtosecond companies, the authors of the journal articles will be color coded red for financial ties and green if not. (The lead author will be in redif at least one of the authors has financial ties.)

7. Capsulorhexis Hypothesis: a capsulorhexis (rhexis) should overlap the IOL optic approximately .5 mm symmetrically 360 degrees and be larger than 4 mm . This will give a better and more consistent effective lens position (ELP) because of less asymmetric contractile force from the fibrosing anterior capsule on the IOL. The IOL should then not position more anteriorly or posteriorly than anticipated or with decentration or tilt. 1,2,3 A better ELP leads to: Closer to targeted spherical equivalent and less cylinder a. Better uncorrected distance vision (UCDVA) 2. Less higher order aberrations like spherical aberration and tilt a. Better corrected distance vision (CDVA) b. Better quality of vision with less glare, halos, and better contrast sensitivity.

8. The femto anterior capsulotomy is more precise (consistent) and more accurate than a manual curvilinear capsulorhexis (CCC). Better size, more circular, better centered thus better overlap of the IOL. And better overlap yields less IOL decentration and tilt and better anterior-posterior position. Claim of the Femtolaser Companies: CCC vs. Femto Buttons Assymetric Overlap Decentered IOL 4,5 4 5 Friedman; JCRS; 2011 Kranitz; JRS; 2011

9. Scientific Background  Continuous curvilinear capsulorhexis (CCC) technique was developed simultaneously by Neuhann in Germany and Gimbel in Canada around 1987. 6,7  Prior rhexis techniques (eg. can opener) led to 100% anterior capsular tears during cataract surgery and CCC tear rate approached 0%. 8  Prior to CCC capsular tears led to IOL’s with haptics commonly with one in the bag and one in the sulcus or with both in the sulcus.

10. Continuous Curvilinear Capsulotomy: A Revolutionary Change for IOL Positioning 9 Assia, Apple (Oph 1993) showed:  Bag-Sulcus Fixation mean Decentration= .64 ± .39mm (range up to 1.76mm) Note: 1 SD =66.6% thus: 1.0mmdecentration was common  Bag-bag Fixation mean Decentration= .18 ± .09

11. Clinical Studies in the CCC Era Measuring IOL Decentration and Tilt Mean follow-up= 12.2 months Range= 3 to 48 months 10 Mean IOL decentration 0.28 ± .16 mm and tilt 2.61 ± 1.2°

12. How Much Does 0.28 ± .16mm Decentration and 2.6° ± 1.2° Tilt Effect Vision? Would evenlessdecentration and tilt provide better UCVA and CDVA? Would even less decentration and tilt provide better contrast sensitivity and less glare and halos? Would even less decentration and tilt have more or less effect depending on whether the IOL is spherical, negative aspheric, neutral aspheric, accommodating, multifocal? Let`s look at the Non-FemtoLiterature first….

13. Remember: Femto Companies Claim • Better Rhexis → Better ELP → Better Vision • Better Vision can mean both smaller refractive error and better quality of CDVA. • Okada has shown that a better rhexis does NOT lead to a Smaller Refractive Error (spherical equivalent or cylinder.) • Okada (Oph 2014) : Does the Rhexis Circularity or Centration effect Post-op Refractive Error? •  93 eyes •  Phacomostly by residents •  Pre-op spherical equivalent -7.75 to +4.50 •  Alcon Spherical IOL (SN60AT) • Results for One Month and 1 year • Measurements: •  RhexisCircularity (comparison to • perfect circle; ratio 1.0=perfect) •  Rhexis (not IOL) Decentrationfrom • pupil center •  Complete Overlap of Rhexis • (360 over the IOL Optic) yes or no 11

14. Okada Results (Cont’d): (Stabilization Change from 1 Month to 1 Year) Over time the rhexis became more circular, lessdecentered and with more overlap.

15. Okada Results (Cont’d) Circularity of Rhexis  NO significant correlation of circularity with post-op target spherical equivalent at 1 month or 1 year  NO significant correlation of circularity with post-op cylinder at 1 month or 1 year

16. Okada Results (Cont’d) • Decentration of Rhexis • NO correlation with change in cylinder from 1 month to 1 year. It did correlate with the change in spherical equivalent between 1 month and 1 year (p=.03). • But Bottom Line: • NO significant correlation of Decentration with post-op target spherical equivalent at 1 month or 1 year. •  NO significant correlation of Decentration with post-op cylinder at 1 month or 1 year.

17. Okada Results (Cont’d) • 360° Overlap vs. Incomplete Overlap • → NO correlation with change in spherical equivalent between 1 month and 1 year. It did correlate with change in cylinder between 1 month and 1 year. • But Bottom Line: •  NO significant correlation of Overlap with post-op target spherical equivalent at 1 month and 1 year • NO significant correlation of Overlap with post-op cylinder at 1 month and 1 year

18. Conclusion:  Rhexis Centration and Circularity and Overlap do not correlate with Post-op Refractive error.  Rhexis Centration and Overlap do play some role in stability of refraction but not enough to effect the average post-op refractive error at one year.

19. Effect of IOL Position on Quality of Vision • Remember, Femto companies hypothesize: Better Overlap → Better IOL Position → Better Vision • Okada’s Study Showed: Better Overlap Does Not → Better Refractive Error • Question: Could Better Overlap → Better Quality of Vision • Lower order Aberrations: myopia, hyperopia, astigmatism • Higher Order Aberrations (HOA’s): coma, spherical aberration, trefoil, etc. can effect the quality of vision. These are measured with a wavefront analyzer. • Decentration and Tilt may effect Aspheric IOL’s more than spherical IOL’s so we will spend some time reviewing this subject now.

20. Effect of IOL Position on Quality of Vision (Cont’d) • Remember this: • The larger the pupil the more HOA’s there are. • The pupil size increases in dim light and decreases with age. •  55 years old (cataract age) pupil diameter: • Bright mesopic= 3.2mm • Mesopic= 4.0mm • Low Mesopic= 5.0mm 12

21. Effect of IOL Position on Quality of Vision (Cont’d) Aspheric IOL’s  The First Negative Aspheric IOL was Tecnis (Pharmacia now AMO). Holladay and Piers did the early theoretical research for Pharmacia. • Basic Idea: • A. The amount of total eye spherical aberration could be manipulated with an IOL because spherical aberration unlike other HOA`s like coma and trefoil is not very sensitive to the position of the IOL (rotation, decentrationand tilt). However decentration and tilt could still possibly effect the results. • B. The cornea has positive asphericity and this is stable despite aging. It is approximately +.27. The lens has negative asphericity to balance the cornea so the total eye spherical aberration is minimized. The lens becomes more positively aspheric after age 40 causing more total eye positive asphericity. 41 y.o. 6.0mm pupil mean s.a.=.10 65 y.o. 6.0 pupil mean s.a=.19 13

22. A spherical IOL has positive asphericity which increases the spherical aberration of the eye. Pharmacia developed a -.27 negative aspheric IOL (Tecnis) to eliminate total eye spherical aberration and thereby improve the quality of vision eg., contrast sensitivity. Tilt and decentration can induce HOA`s but much more in a negative aspheric IOL than a spherical IOL. Question: Would tilt and decentration be a problem with negative aspheric IOL`s?

23. 14 Holladay and Piers (JRS 2002) They calculated the Modular Transfer Function (MTF) at different amounts of tilt and decentration. MTF is a mathematical/theoretical calculation of contrast (the contrast of an image relative to the contrast of the object traveling through an optical medium). This relates to quality of vision. Amount of tilt and decentration of Tecnis where the MTF (quality of vision) becomes worse than a spherical IOL: Decentration= 4mm Tilt= 7° Holladay used monochromatic light for his calculations. In 2007 Piers corrected the calculations based on the more physiologic polychromatic light we experience: Decentration= .8mm Compare to 0.28 ± .16mm actual mean decentration of IOL’s with a CCC Tilt= 10° Compare to 2.6 ± 1.2° actual mean tilt of IOL’s with a CCC 15

24. Piers’ Graph lawless lawless Polychromatic MTF Polychromatic MTF 10° 3.8° .44 .28 0.8 2.6° Decentration Tilt 16 Decentration .28 ± .16 → .44mm Note: Minimal effect on MTF for most patients. Tilt 2.6 ± 1.2° → 3.8° Note: Tilt effects MTF even less than decentration. Ignore top dotted line (theoretical IOL with all HOA’s corrected) Solid line= Tecnis Dashed line= Spherical IOL

25. Aspheric IOL Clinical Studies 17,18,19 Kohnen`s team in Germany A series of intraindividual studies (same patient with one eye spherical IOL and other eye Tecnis). • Spherical aberration was less with Tecnis at all pupil sizes (the bigger the pupil the larger the difference). • Total HOA`s were lower with Tecnis only if pupil  6.0 mm (most cataract patients’ pupils are smaller) and coma and trefoil were no different at all pupil sizes. • Even though spherical aberration was less, Tecnisgave no improvement in CDVA photopic with high contrast charts or mesopic low contrast charts. • Tecnis gave no improvement in Contrast Sensitivity photopicor mesopic.

26. Kohnen (Cont’d) 5. Were these less than expected results with Tecnis due to tilt and decentration? a) The Kohnen group measured it: Tecnis: decentration= 0.27 ± .16mm (as expected from other studies) tilt= 2.9 ± 1.5° (as expected from other studies) (Decentration and Tilt of Spherical IOL’s studied were almost exactly the same.) b) Multiple Regression Analysis showed no statistically significant correlation between decentration or tilt with the HOA’s. ie, Decentration and Tilt were not the reason why Tecnis performed worse than expected. c) This is consistent with the Piers graphs: Decentration and Tilt with a CCC are too small to significantly effect HOA’s even with negative aspheric IOL’s.

27. So why didn’t Tecnis eyes see better? They had significantly less spherical aberration and we know decentration and tilt were too small to effect that impact. Puzzling…. Possible explanations: a) Pupil size: average pupil in the study in mesopic conditions was 3.8mm. Negative spherical correcting IOL’s have a much larger effect in pupils  6.0mm. b) Interactions with other HOA’s. It is not just spherical aberration we are dealing with. Some HOA’s may interact with others in a negative or positive way. Take home message:  Factors effecting quality of vision are complex. (Marketing companies may use that to their advantage.)  Negative aspheric IOL’s are not significantly effected by decentration and tilt for most patients. 20

28. Neutral Aspheric IOL Studies Developed Several Years Later Concept 1. Do not add or subtract from the total eye spherical aberration. 2. Neutral aspheric IOL’s may not actually decrease the total eye spherical aberration but they are less effected by decentration and tilt than negative spherical IOL’s.

29. Modulation Modulation ModulationModulation Tecnis Negative Aspheric .4 .4 .4 .4 Modulation Soft Port Neutral Apheric Modulation Spheric 21 Eppig (JCRS 2009) 21 •  Model Eye Study calculation of MTF with Decentration; comparing Aspheric, Neutral Aspheric, & Spherical • IOL’s. • Two pupil sizes and three types of IOL’s. • Verticle lines = .3 and .4mm decentration from the literature. (Mean and with one standard deviation.) •  Monochromatic light (Holladay) was used. Slope should be less narrow as per Piers/ Polychromatic light. • Decentration has no effect on neutral aspheric and spherical IOL.. •  Tecnis is more beneficial in larger pupil.

30. 22 Tilt has minimal effect on Tecnis even with monochromatic MTF calculations.

31. 23 Johansson (JCRS 2007) Swedish Multicenter Double masked study of 80 patients with Tecnis in one eye and Neutral aspheric Akreos in the other. Results (3 months post-op):  Total HOA`s less for Tecnis for 4, 5 and 6mm pupils (p <.01)  Spherical Aberration less for Tecnis for all pupils (p<.o001) Nevertheless:  No difference in CDVA mesopic and photopic with high or low contrast charts.  No difference in contrast sensitivity mesopic or photopic  Depth of field better with Acreos (p=.002) Patient Questionnaire: Subjective Visual Quality: Preferred Akreos 2X more (p<.001) Complaints of Visual disturbances Tecnis 3X more (p<.001)

32. Why was vision no better with Tecnis than Neutral Aspheric even though Tecnis had decreased HOA’s in this study? Remember: Kohnen showed vision no better with Tecnis than Spherical IOL. They suggested (1) Small mean pupil size in cataract population. (2) Interplay of HOA’s. Johansson suggests for neutral aspheric comparison 1. Better depth of field with neutral aspheric 2. Different IOL design/material

33. Things We Have Learned So Far:  Decentration and Tilt have only minor effect on Negative Spherical IOL’s and even less on Neutral Aspheric and Spherical IOL’s. Factors Effecting Quality of Vision are Complex.  Negative Aspheric IOL’s may not perform any better than Spherical IOL’s.  Neutral Aspheric IOL’s may perform better than Negative Aspheric IOL’s.  Femto Companies Suggest that better IOL Centration and Tilt Improves Vision with All IOL’s but Especially with Aspheric IOL’s, Multifocal IOL’s, and Accomodating IOL’s. Now you have the background to better evaluate such claims pro or con.

34. How Much Does 0.28 ± .16 Decentration and 2.6° ± 1.2° Tilt Effect Vision? Not much. Would evenlessdecentration and tilt provide better UCVA and CDVA? Would even lessdecentration and tilt provide better contrast sensitivity and less glare and halos? Would even less decentration and tilt have more or less effect depending on whether the IOL is spherical, negative aspheric, neutral aspheric, accomodating, multifocal? Probably Not. Let`s See What the Femto Literature Has to Say….

35. CCC vs. Femto Buttons Assymetric Overlap Decentered IOL 4 5 4 5 Claim of the Femtolaser Companies: Better Rhexis → Better ELP → Better Vision

36. Studies: Rhexis, Size, Shape, Centration: Femto vs. Phaco Names in Red= Financial Ties Green= No Financial Ties 24 25 26 27 28 29 30 * Human Eye Studies Femto→ Rounder, Better Size and Centration → Better Overlap

37. Does a better Femto Rhexis Yield Better results? • Kranitz(surgeon Nagy)LenSx (JRS 2011) •  20 Femto Human vs. 20 Phaco Cases •  Decentrationof the IOL was better with Femto at 1 month and 1 year • At 1 year femto .15mm ± .12 and Phaco.30mm ± .16 (p<.05) 31 This is comparing spherical IOL’s. Remember the Piers Graph for Aspherics? Piers’ Graph Even for Asheric IOL’s the Difference between 0.15mm and 0.3mm is minor. It doesn’t mean much. 0.30 0.15 16

38. Kranitz(cont’d) Effect of Decentration on Neutral Aspheric and Spherical IOL’s. Softport AO Neutral Aspheric Eppig Graph It doesn’t mean ANYTHING. Softport AO Spherical

39. 32 Mihaltz(surgeon Nagy) LenSx (JRS 2001) 48 Femto and 51 PhacoCases with Spherical IOL`s. 6 Month Post-op Refractive Error and HOA’s No Difference in Refractive Error:  Deviation from Intended spherical equivalent (p>.05)  Amount of Cylinder and UDVA and CDVA (p>.05) Ocular Higher Order Aberrations (4.5 virtual pupil):  No Difference in any HOA`s.  MTF (theoretical quality of vision calculated from the contrast sensitivity calculated from the HOA`s) better for Femto(p<.05) even though there was no significant difference in HOA’s between Femto and Phaco with Spherical IOL’s

40. 33 • Kranitz(surgeon Nagy) (JRS 2012) • LenSx20 Femto and 25 PhacoCases with SphericalIOL`s. • Measured IOL Tilt and Decentration •  Femto Tilt: 2.2° ± 1.4° • Phaco Tilt: 4.3° ± 2.4° • Femto better (p=.001) •  FemtoDecentration: 0.23 ± .11mm (this is close to literature decentration of 0.28) • PhacoDecentration: 0.33 ± .17mm • Femto better (p=.02) •  UCDVA No Difference •  Deviation from Target Refraction no significant Difference • CDVA Femto better at 1 month and 1 year (p-.03 and .04 • respectively). (Only Study even among Red • highlighted ones with this result) • Kranitz Explanation for • Better CDVA: Tilt Correlated • With CDVA Note: 4.3° tilt with Phaco IOL’s is higher than the mean tilt in the literature (.26° ± .12°). Eppig Graph Neutral Aspheric Really? Spherical

41. 34 Filkorn(surgeon Nagy)(JRS 2012) LenSx Femto 77 and Phaco57 Cases with SphericalIOL`s. 3 Month Post-op Refractive Error (Included -20D to +7D pre-op )  Deviation from Target spherical equivalent Femto: .12D better that Phaco(p=.04) (Only study reporting better spherical equivalent).  CDVA No Difference

42. 35 Lawless 61 Femto and 29 Phaco All Restor Multifocals No Significant Difference Even In a Multifocal Where Centration Should Be Most Significant: Deviation from Target spherical equivalent: No Difference Amount of cylinder : No Difference UDVA, CDVA, UNVA: No Difference Note Deviation from Spherical Equivalent Target Femto: 0.26 ± .25 (range -.10 to 1.18) Phaco: 0.23 ± .16 (0 to .52). p=.54 But….

43. Lawless(cont’d) Deviation from Targeted Spherical Equivalent Femto Phaco Standard Deviation ± .39 Range -.75 to +1.25 Standard Deviation ± .32 Range -.50 to +1.75 LESS SCATTER, SMALLER SD AND RANGE WITH PHACO

44. Abe11 100 Femto and 100 Phaco 3 week post-op  No difference between Femto and Phaco in Deviation from target spherical equivalent or CDVA 36

45. Femto vs. Phaco Vision 32 33 34 35 36 only study even among the red with this result

46. Remember this Question? How Much Does 0.28 ± .16 Decentration and 2.6° ± 1.2° Tilt Effect Vision? Would evenlessdecentration and tilt with Femto provide better UCVA and CDVA? Answer: No. Would it provide better contrast sensitivity and less glare and halos? No studies to date have tested this. …Why not? Why no intraindividual comparison of Femto and Phaco and measuring mesopic vision on low contrast charts (most sensitive visual acuity test for visual quality), or measuring contrast sensitivity photopic,mesopic with and without glare? Why no patient questionnaires as to which eye they like better? Would less decentration and tilt with Femto have more or less effect depending on whether the IOL is spherical, negative aspheric, neutral aspheric, accomodating, or multifocal? The studies to date have tested Femto vs. Phaco with Spherical IOL’s and a Multifocal. Answer So Far: NO

47. Rhexis Smoothness and Strength Prior to Neuhannand Gimbel`s CCC anterior capsule capsular tears occurred 100% of the time. The smooth edge of the CCC rhexis is very resistant to tearing. However making a CCC in pediatric cases is more difficult because the capsules are more elastic than in adults and the rhexis tends to run off to the periphery during manual CCC. In the 90`s new devices were tried in order to facilitate the CCC. These included vitrectors, diathermy and the Fugo “plasma blade”. 8

48. Researchers compared these techniques to CCC. It turned out that manual CCC was the Gold Standard and none of the techniques were as good. They looked at 2 things: 1)smoothness of the edge: PhacoMuch Smoother than all other techniques Scanning electron micrographs (SEM’s) of the anterior capsular edge 37,38,39,40 Vitrectorhexis CCC Can Opener CCC Obviously the Smoothest Radio-Frequency Diathermy Plasma Blade

49. Smoothness and Strength (Cont’d) 2) Resistance to capsular tearing All studies showed that a CCC had a significant higher amount of stretch prior to tearing as well as higher amount of force required to tear the rhexis edge. It was assumed the rough edges with other techniques made it prone to tear the edge. The studies used 2 pins usually on calipers (each pin about 1 mm in diameter) and they opened the pins within the rhexis and measured how far the rhexis stretched prior to tearing. Some of the pins were attached to a device that could measure the force required to reach the tearing point. 38

50. Smoothness and Strength How to Study It (Cont’d) What We Learn From the Blue Dye Studies Blue Dye is used in cases when the cataract is so advanced that visualization of the anterior capsule during making of the manual CCC is difficult (poor red reflex). Staining the anterior capsule is very helpful for visualization. Several Studies have been done to see whether blue dye alters the capsule properties. It has been shown to decrease elasticity and increase stiffness of the capsule. To test whether blue dye reduces the rhexis` resistance to tearing Jaber, Werner, Mamalis at Moran Eye Center at the University of Utah did a study (with help from a grant from Alcon). Instead of narrow diameter pins stretching the rhexis they devised a testing device to more closely “simulate forces and displacements that the CCC might withstand during hydrodissection and nucleus cracking and chopping”. They used two 4.4mm shoetree shaped fixtures totaling 8.8mm attached to a force measuring device. There was no difference (with or without blue dye) in the force required to tear the edge of the rhexis even though the rhexis is stiffer with blue dye. The shoetree type of device used in this study may be relevant to how femtorhexis strength has been studied today. 41,42,43,44 45,46,47