Comparative Global Literature Review of Visual and Optical Quality of Refractive, Diffractive, and Hybrid IOL Designs James P. McCulley, MD Department of Ophthalmology University of Texas Southwestern Medical Center at Dallas Dr. McCulley is a consultant for Alcon Laboratories, Inc.

23 unique journal articles Purpose & Methods PURPOSE: To investigate whether trends in superiority exist for optical characteristics and patient outcomes when making pairwise comparisons between 2 of the following 3 IOL types: refractive, diffractive, and hybrid of refractive with apodized diffractive. METHODS: Literature searches for published articles OvidSP Database (MEDLINE, EMBASE pooled), JRS, and JCRS Keyword search #1: refractive AND diffractive AND (multifocal OR bifocal) AND intraocular lens Keyword search #2: compar* AND (multifocal OR bifocal) NOT monofocal AND intraocular lens Keep only the applicable comparative studies 23 unique journal articles *Wildcard asterisk returns “comparative,” “compared,” “comparison,” etc. All results restricted to English language

Methods: Pooled Source Data 23 studies (5 bench, 18 human); total 1411 eyes (Full-Optic) Diffractive IOLs Refractive IOLs Hybrid IOLs (Refractive Outer Ring, Apodized Diffractive Center Disk) Model Studies, n Tecnis®, AMO 11 Array®, AMO 12 ReSTOR®, Alcon 17* CeeOnTM, Pfizer 6 ReZoom®, AMO 10 A-TwinTM, Acri.Tec 3 A-LISATM, Acri.Tec 2 825x +4, 3M 1 Study designs Bilateral groups: 9 studies Contralateral: 1 study By eye: 8 studies Bench: 5 studies Older IOL names or manufacturers updated to most recent. *16 Spherical SN60D3 or SA60D3, 1 Aspheric SN6AD3, 0 Aspheric SN6AD1

Lens Characteristics Tecnis® A-LISATM ReZoom® ReSTOR® Diffractive IOLs Refractive IOLs Hybrid IOLs Tecnis® A-LISATM ReZoom® ReSTOR® Lens Type Multi- Piece Single- Piece Multi- piece Single- or Multi-Piece Lens Material Polysiloxane or acrylic Foldable acrylate with 25% water content, hydrophobic surface, and UV-absorber Hydrophobic acrylic optic, poly-methyl methacrylate (PMMA) haptics UV-absorbing & blue light filtering acrylate/ methacrylate copolymer

Results: Optical Bench Test Outcomes 5 Studies; 5 result types; 18 pairwise superiorities Outcomes included defocus transfer function, night driving photograph, modulation transfer function (near, distance, various pupil sizes), Strehl ratio, USAF target resolution Top three superiorities (others only 1 superiority) Hybrid IOLs superior over refractive IOLs, n=6 Diffractive IOLs superior over refractive IOLs, n=5 Hybrid IOLs superior over diffractive IOLs, n=4 Diffractive vs… Refractive vs… Hybrid vs… Winners Results were not tabulated unless a superiority was observed (ie, equivalences and similarities not counted)

Results: Near Visual Acuity (≤40 cm) 14 of 18 studies found pairwise near VA superiorities Includes UCVA, BCVA, photopic (± glare), mesopic (± glare), defocus curve data, monocular/binocular, various contrast levels Top three superiorities: Diffractive IOLs superior over refractive IOLs, n=26 Hybrid IOLs superior over refractive IOLs, n=8 Hybrid IOLs superior over diffractive IOLs, n=5 Diffractive vs… Refractive vs… Hybrid vs… Winners Results were not tabulated unless a superiority was observed (ie, equivalences and similarities not counted)

Results: Intermediate Visual Acuity (>40 cm to 3 m) 10 of 18 studies found pairwise intermediate VA superiorities Includes UCVA, BCVA, photopic (± glare), mesopic (± glare), defocus curve data, monocular/binocular, various contrast levels Trends in superiority were not consistent: In refractive vs diffractive IOLs: 7 for refractive, 5 for diffractive In diffractive vs hybrid IOLs: 5 for diffractive, 1 for hybrid In refractive vs hybrid IOLs: 5 for refractive, 0 for hybrid All hybrid studies were for +4.0 D IOLs, not +3.0 D IOLs Diffractive vs… Refractive vs… Hybrid vs… Winners Results were not tabulated unless a superiority was observed (ie, equivalences and similarities not counted)

Intermediate Visual Acuity: SN6AD1 versus SN6AD3 IOLs The new +3.0 D IOL (SN6AD1) uses the existing +4.0 D IOL (SN6AD3) platform Vergence, D 40 cm 33 cm 50 cm Visual acuity, logMAR Intermediate visual acuity is improved with +3.0 D IOL Near focus is farther out from the eye with +3.0 D IOL Maxwell et al. J Cataract Refract Surg. 2009: 35; 2054-2061

Results: Far Distance Visual Acuity (>3 m) 4 of 18 studies found pairwise far VA superiorities Includes UCVA, BCVA, photopic ( photopic + glare, mesopic, mesopic + glare, defocus curve data, monocular/binocular, various contrast levels Top three superiorities: Hybrid IOLs superior over diffractive IOLs, n=8 Tie for second place: refractive vs diffractive, 2 superiorities each Diffractive vs… Refractive vs… Hybrid vs… Winners Results were not tabulated unless a superiority was observed (ie, equivalences and similarities not counted)

Underpowered/Unclear Comparisons Visual disturbances: superiorities found by 2 of 7 studies Diffractive > Refractive, negative dysphotopsia (n=1) and halo (n=1) Contrast sensitivity: superiorities found by 7 of 9 studies Various spatial frequencies and lighting conditions Diffractive>Refractive, n=3 Hybrid>Refractive, n=3 Refractive>Diffractive, n=4 Refractive>Hybrid, n=3 Higher-order aberrations: superiorities found by 3 of 4 studies Included coma, spherical aberration, various pupil sizes Hybrid>Refractive, n=12 results Diffractive>Hybrid, n=8 results Reading acuity and speed: superiorities found by 3 of 3 studies Various lighting conditions, distances, correction Top acuity superiority: Diffractive > Refractive (n =15 results) Top speed superiority: Diffractive > Refractive (n=9 results)

Summary Based on the number of results from articles comparing one type of multifocal IOL to another, the following possible trends were observed: For published optical quality results, Hybrid > Refractive Diffractive > Refractive For published visual acuity results, Near vision Hybrid > Diffractive Intermediate vision Refractive vs diffractive: differences not clear Refractive and diffractive superior to hybrid (+4.0 D model), but SN6AD1 (+3.0 D model) improves intermediate visual acuity Distance vision Tie for second place: Refractive vs Diffractive Superiority results were less clear for visual disturbances, contrast sensitivity, higher-order aberrations, reading acuity, reading speed

References (Database for Literature Review) Alfonso et al. J Cataract Refract Surg 2008;34:1848-1854. Alio et al. J Cataract Refract Surg 2004;30:2494-2503. Artigas et al. J Cataract Refract Surg 2007;33:2111-2117. Chang. J Cataract Refract Surg 2008;34:934-941. Chiam et al. J Cataract Refract Surg 2007;33:2057-2061. Choi et al. J Refract Surg 2008;24:218-222. Gunenc et al. J Refract Surg 2008;24:233-242. Hutz et al. J Cataract Refract Surg 2006;32:2015-2021. Hutz et al. J Refract Surg 2008;24:251-256. Maxwell et al. J Cataract Refract Surg 2009;35:166-171. Mester et al. J Cataract Refract Surg 2007;33:1033-1040. Ortiz et al. J Cataract Refract Surg 2008;34:755-762. Palmer et al. J Refract Surg 2008;24:257-264. Pepose et al. Am J Ophthalmol 2007;144:347-357. Pieh et al. Arch Ophthalmol 2002;120:23-28. Renieri et al. Eur J Ophthalmol 2007;17:720-728. Richter-Mueksch et al. J Cataract Refract Surg 2002;28:1957-1963. Schmidinger et al. J Cataract Refract Surg 2006;32:1650-1656. Schwiegerling. J Refract Surg 2007;23:965-971. Toto et al. J Cataract Refract Surg 2007;33:1419-1425. Walkow et al. Ophthalmology 1997;104:1380-1386. Weghaupt et al. J Cataract Refract Surg 1998;24:663-665. Zelichowska et al. J Cataract Refract Surg 2008;34:2036-2042.