Glistenings in Alcon Acrysof Intraocular Lenses GEORGE H.H. BEIKO, B.M.,B.Ch.,FRCSC ST. CATHARINES, CANADA ASSIST PROF, MCMASTER UNIV LECTURER, UNIV OF TORONTO george.beiko@sympatico.ca

GRADE 3+ 5500 10µm

DJ Apple AAO 2008

ASCRS sent out alert on “glistenings”on March 16, 1995.

DJ Apple AAO 2008

DJ Apple AAO 2008

DJ Apple AAO 2008

Factors Influencing Glistenings Different degrees of glistenings were found in all foldable IOLs manufactured from all materials (including 2 silicone, 3 hydrophilic acrylic, and 2 hydrophobic acrylic (Acrysof and Sensar)). The percentage of patients with glistenings generally increased up to 90 days postoperatively and then became stable in all groups, with the exception of the AcrySof IOL group, which had a continuous increase over time (up to 720 days). Tognetto D, et al. Glistenings in foldable intraocular lenses. J Cataract Refract Surg 2002; 28:1211–1216

Glistenings Formation in Hydrophobic Acrylic* Non-homogenous polymerization of optic material allows gaps to form; water vapour collects in these gaps; temperature changes allow water droplets to form Light is refracted and scattered at the water–polymer interfaces, leading to a sparkling appearance of the fluid-filled vacuoles (thus, the term glistenings). The size of individual glistenings range from 1 to 20 mm Manufacture by molding results in greater number of gaps than lathe cutting The combination of injection molding and temperature sensitivity leads to significantly more glistening formation with AcrySof™ IOLs Nishihara H, et al. [Glistenings in lathe-cut acrylic intraocular lens]. [Japanese] Ganka Shujutsu 2000; 13:227–230 Miyata, et al. Equilibrium water content and glistenings in acrylic intraocular lenses. J Cataract Refract Surg 2004; 30:1768–1772 Werner L. Glistenings and surface light scattering in intraocular lenses. J Cat Refract Surg. 2010 36: 1398-1420.

Glistenings Formation in Hydrophobic Acrylic* “that glistenings (referred to as cavitation) are the result of relatively slow-moving hydrophilic impurities …represented by oligomeric species that contain some fraction of hydrophilic monomers, are generated during polymerization. They would preferentially segregate out of the matrix material into polymer voids (cavities), giving rise to an osmotic pressure difference between the cavity and the external media in which the IOL is immersed.” “the influx of water into the cavity deforms the surrounding polymer until the stress reaches a critical value when permanent deformation occurs (ie, cracking or tearing) and the cavity grows. This process would continue until equilibrium is achieved.” Saylor DM, et al. Osmotic cavitation of elastomeric intraocular lenses. Acta Biomater 2010; 6:1090–1098

Factors Influencing Glistenings Mean density score of glistenings is higher if lenses are incubated in aqueous humour with serum at body temperature Diabetes: Occurrence of glistenings was 46.5% among nondiabetic patients but 75.5% among diabetic patients. If considering cases with grade 3C of the Miyata scoring system, 5.5% of the patients were not diabetic and 20.5% were diabetic. Glaucoma: Statistically significant association between the incidence and severity of glistenings and glaucoma. Authors unsure if effect was due to glaucoma or antiglaucoma medications Depression: Glistenings were associated with depression. Mitooka K, Tsuneoka H. [Glistening – changes that occur to the intraocular lens]. [Japanese]. In: Maruo T, Honda Y, Usui M Tano Y, eds, [Practical Ophthalmology] [Japanese]. Tokyo, Japan, Bunkodo Publishers, 1999; 66–67. Dick HB, et al. Vacuoles in the AcrySof intraocular lens as factor of the presence of serum in aqueous humor. Ophthalmic Res2001; 33:61–67 Moreno-Montane´s J, et al. Clinical factors related to the frequency and intensity of glistenings in AcrySof intraocular lenses. J CataractRefract Surg 2003; 29:1980–1984 Colin J, Orignac I, Touboul D. Glistenings in a large series of hydrophobic acrylic intraocular lenses. J Cataract Refract Surg 2009; 35:2121–212.

Glistenings Patient with Acrysof in one eye and silicone in other eye Courtesy of J. Singer

Glistenings Patient with Acrysof in one eye and PMMA in other eye Courtesy of J. Singer

Glistenings Acrysof IQ Acrysof ReSTOR Courtesy of J. Singer

Determining Severity Grade of Microvacuoles Scattering Area (% of 2 x 2 mm) Numbers Typical Sizes Description 1 < 0.5% 0-50 20μ Mild 2 < 2% 51-250 Moderate 3 < 10% 251-2500 High 4 > 10% > 2500 10μ Severe

Determining Severity Grade of Microvacuoles Courtesy of R. Olson

In House Prevalence Study 20 Patients Recalled at Random 6 Groups: 1Day Post-OP 6 Months Post Op (+-1 Month) 1 Year Post Op (+- 2 Months) 2 Years Post-Op (+- 3 Months) 3 Years Post-Op (+- 4 Months) 4+ Years Post-Op L. Fry, ASCRS 2008

Results: 1 Day: 0/20 6 Months: 3/20 (1-1+; 2-2+) 1 Year: 7/20 (5-1+, 2-2+) 2 Years: 13/21 (5-1+, 8-2+) 3 Years: 21/25 (10-1+,9-2+, 2-3+) 4+ Years: 9/20 (6-1+, 3-2+) L. Fry, ASCRS 2008

Preliminary Conclusions: Glistenings in Acrysof Acrylic IOLs are not present on day one, but appear to be acquired, increasing in both incidence and severity with time, affecting the majority of Implanted Lenses by 3 years 1+ and 2+ Glistenings do not appear to significantly affect Vision, Glare Disability, or Contrast Sensitivity; 3+ glistenings may adversely affect Vision, Glare and Contrast L. Fry, ASCRS 2008

Glistenings, Incidence 42 patients, AcrySof MA30BA or MA60BM, 2.4 years =/- 0.3 (SD) (range 6 to 46 months) after implantation, all IOLs had glistenings. 53 consecutive patients with the SA60 IOL at 12, 24, and 36 months and patients with the SN60 at 12 months; all 53 IOLs showed some degree of glistenings. 115 eyes, AcrySof MA60BM no glistenings were found 1 month after surgery;20% at 3 months, 51% at 6 months, and 55% at 1 year. 115 eyes implanted, AcrySof MA60BM, incidence of 55.7% at 14 months and 87.3% at 28 months. Miyata A, et al. [Glistening particles on the implanted acrylic intraocular lens]. [Japanese] Rinsho Ganka 1997; 51:729–732. Miyata A, et al. [Clinical and experimental observation of glistening in acrylic intraocular lenses]. [Japanese] Nippon Ganka Gakkai Zasshi 2000; 104:349–353 Peetermans E, Hennekes R. Long-termresults of Wagon Wheel packed acrylic intra-ocular lenses (AcrySof). Bull Soc Belge Ophtalmol 1999; 271:45–48 Christiansen G, et al. Glistenings in the AcrySof intraocular lens: pilot study. J Cataract Refract Surg 2001; 27:728–733. Tognetto D, et al. Glistenings in foldable intraocular lenses. J Cataract Refract Surg 2002; 28:1211–1216. Moreno-Montane´s J, et al. Clinical factors related to the frequency and intensity of glistenings in AcrySof intraocular lenses. J CataractRefract Surg 2003; 29:1980–1984. Waite A, Faulkner N, Olson RJ. Glistenings in the single-piece, hydrophobic, acrylic intraocular lenses. Am J Ophthalmol 2007; 144:143–144

DJ Apple AAO 2008

Glistenings Present in all Acrysof Lenses and Continue to Increase with Time Behndig A, Monestam E. Quantification of Glistenings in Intraocular Lenses using Scheimpflug Phtography. J Cat Refract Surg 2009; 35: 14-1

The Light Scatter Effect: Comparison of Acrylic Materials Van der Mooren M, Coppens J, Bandhauer M, Van den Berg T. Presented at ARVO 2007.

Backward scatter 10mm 80µm Forward scatter

The Light Scatter Effect: Comparison of Acrylic Materials* The forward light scatter of AcrySof™ lenses is relatively large compared to the backward scatter, so functional significance may be underestimated in the clinic Initially, scatter of all IOLs was < 20yr old healthy crystalline lens Lenses with glistenings can cause scatter greater than that present in a 70 year old’s crystalline lens *Van der Mooren M, Coppens J, Bandhauer M, Van den Berg T. Presented at ARVO 2007.

The Light Scatter Effect: Comparison of Acrylic Materials* With multifocal IOLs, backward scatter is similar but forward scatter is greater with the ReSTOR *Van der Mooren M, Coppens J, Bandhauer M, Van den Berg T. Presented at ARVO 2007.

J Colin AAO 2010

Acrysof lenses, J Colin, 2010

Vision as predicted by lowest grade of gisitenings, from Colin data, AAO 2010 Simulations by T. Van der Berg

Vision as predicted by lowest grade of gisitenings, from Colin data, AAO 2010 Simulations by T. Van der Berg

Clinical Significance of Glistenings Glistenings, unless very severe, do not adversely affect the MTF, UV/Visible spectral transmittance, light scattering and resolving power performance of intraocular lenses Oshika T, et al. Influence of glistenings on the optical quality of acrylic foldable intraocular lens. Br J Ophthalmol 2001; 85:1034–1037.1 Loss in contrast sensitivity A study on visual function has shown that glistenings in AcrySof™ IOLs (MA30BA and MA60BA) were related to a statistically significant loss of up to 40% in contrast sensitivity at high spatial frequencies (12 cycles per degree) Gunenc U, et al. Effects on visual function of glistenings and folding marks in AcrySof intraocular lenses. J Cataract Refract Surg 2001; 27:1611–1614 Fry LL, Fry EL, ‘‘Glistenings in Hydrophobic Acrylic IOLs,’’ paper presented at the ASCRS Symposium on Cataract, IOL and Refractive Surgery, Boston, Massachusetts, USA, April 2010 Decreased visual acuity Eyes with higher grades of glistenings had a small but significantly greater decrease in visual acuity than those with lesser grades Christiansen G, et al. Glistenings in the AcrySof intraocular lens: pilot study. J Cataract Refract Surg 2001; 27:728–733

Clinical Significance of Glistenings Search of adverse reports related to glistenings was performed on the FDA web site using the search term ‘‘intraocular lens glistenings’’ 106 records between July 3, 1997 and June 4, 2009 were found 96 were regarding Acrysof lenses in cases with decreased visual acuity or other symptoms leading to a decrease in visual quality Fourteen reports were related to IOL explantation of Acrysof lenses Werner L. Glistenings and surface light scattering in intraocular lenses. J Cat Refract Surg. 2010 36: 1398-1420.

Clinical Significance of Glistenings 1) "We conclude that the Acrysof Natural IOLs do not demonstrate substantial clinical benefit in comparison with currently available IOLs" (p. 1010) 2) "Moreover, in our review......regarding the blue light filtering optic, we found evidence suggesting that the blue-filtering lenses could decrease best possible vision." (p. 1006) 3) "Finally, this commentor stated that the glistenings associated with Acrysof Natural lenses that develops overtime causes disability glare rather than reduces it." (p. 1009) Department of Health and Human Services, Centers for Medicare and Medicaid (2010) when asked to consider the Acrysof Naturale for NT-IOL status, which was declined.

Glistenings “We as a group are the first ones to publish a study with regard to intraocular lens glistenings (1995).” ”We do know that…(glistenings).. occur in the majority if not 100% of all Acrysof lenses over time and that they are clearly continuing to get worse after ten years.” RJ Olson MD, 2010

(introduced concept of UV protection in IOLs,1978) Glistenings “The development and progression of glistenings in AcrySof IOLs is the fault of the optical material manufacturing process, not the surgeon.” Most ophthalmologists would be outraged if glistenings developed in their camera lenses, so it’s surprising that glistenings are often ignored in their patients’ implanted IOLs. " MA Mainster, 2010 (introduced concept of UV protection in IOLs,1978)

Glistenings “The bottom line is that these defects due to the size and nature would not be acceptable for use on NIF (National Ignition Facility) or any other laser ……(or)…any high precision system." D Walmer, 2010 Master Optician, Senior Engineering Associate, Lawrence Livermore National Laboratory The LLNL engineering activities include micro- and nanotechnology, lasers and optics, biotechnology, precision engineering, nondestructive characterization, modeling and simulation, systems and decision science, and sensors, imaging and communications.

Glistenings “one is justified in asking the question "Why implant..(an Acrysof).. lens when the potential for .. (glistenings).. exists, if there is indeed an equivalent quality IOL available that carries out all functions of the lens but is not encumbered with 'glistenings'?” DJ Apple MD, 2010

Which lens would you choose for yourself ?  

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