Opacification of Hydrophilic Acrylic Intraocular Lenses: Overview of Laboratory Methods for Histological Analysis and Replication of IOL Calcification

Abstract

Opacification of intraocular lenses (IOLs) due to material changes is a serious complication that can compromise the good visual outcomes of uncomplicated cataract surgery. In hydrophobic acrylic IOLs, opacification can result from glistening formation, while in hydrophilic acrylic IOLs, there is a risk of calcification due to the formation of calcium phosphates within the polymer. Over time, various methods have been developed to investigate calcification in hydrophilic acrylic IOLs. The aim of this article is to provide an overview of standard histological staining and models used to simulate IOL calcification. Histological staining can be used to detect calcification and assess the extent of crystal formation. The development of in vivo and in vitro replication models has helped to identify the underlying pathomechanisms of calcification. In vivo models are suitable for assessing the biocompatibility of IOL materials. Bioreactors as an in vitro model can be used to investigate the kinetics of crystal formation within the polymer. The replication of IOL calcification under standardized conditions using electrophoresis allows for the comparison of different lens materials with respect to the risk of calcification. The combination of different analytical and replication methods can be used in the future to further investigate the pathomechanisms of calcium phosphate crystal formation and the influence of risk factors. This may help to prevent calcification of hydrophilic acrylic IOLs and associated explantation and complications.

Key words

IOL calcification - opacification - complication - cataract surgery - histology

Publication History

Received: 30 January 2023

Accepted: 29 March 2023

Article published online:
30 June 2023

• References/Literatur

• 1 Grzybowski A. Recent developments in cataract surgery. Ann Transl Med 2020; 8: 1540
• 2 Khoramnia R, Yildirim TM, Labuz G. et al. [Opacification of intraocular lenses: laboratory and clinical findings]. Ophthalmologe 2021; 118: 633-642
• 3 Labuz G, Knebel D, Auffarth GU. et al. Glistening Formation and Light Scattering in Six Hydrophobic-Acrylic Intraocular Lenses. Am J Ophthalmol 2018; 196: 112-120
• 4 Yildirim TM, Auffarth GU, Labuz G. et al. Material Analysis and Optical Quality Assessment of Opacified Hydrophilic Acrylic Intraocular Lenses After Pars Plana Vitrectomy. Am J Ophthalmol 2018; 193: 10-19
• 5 Giers BC, Tandogan T, Auffarth GU. et al. Hydrophilic intraocular lens opacification after posterior lamellar keratoplasty – a material analysis with special reference to optical quality assessment. BMC Ophthalmol 2017; 17: 150
• 6 Kanclerz P, Yildirim TM, Khoramnia R. Microscopic Characteristics of Late Intraocular Lens Opacifications. Arch Pathol Lab Med 2021; 145: 759-767
• 7 Kanclerz P, Yildirim TM, Khoramnia R. A review of late intraocular lens opacifications. Curr Opin Ophthalmol 2021; 32: 31-44
• 8 Drimtzias EG, Rokidi SG, Gartaganis SP. et al. Experimental investigation on mechanism of hydrophilic acrylic intraocular lens calcification. Am J Ophthalmol 2011; 152: 824-833.1
• 9 Gartaganis SP, Prahs P, Lazari ED. et al. Calcification of Hydrophilic Acrylic Intraocular Lenses With a Hydrophobic Surface: Laboratory Analysis of 6 Cases. Am J Ophthalmol 2016; 168: 68-77
• 10 Labuz G, Yildirim TM, van den Berg T. et al. Assessment of straylight and the modulation transfer function of intraocular lenses with centrally localized opacification associated with the intraocular injection of gas. J Cataract Refract Surg 2018; 44: 615-622
• 11 Yildirim TM, Labuz G, Khoramnia R. et al. Impact of Primary Calcification in Segmented Refractive Bifocal Intraocular Lenses on Optical Performance Including Straylight. J Refract Surg 2020; 36: 20-27
• 12 Neuhann T, Yildirim TM, Son HS. et al. Reasons for explantation, demographics, and material analysis of 200 intraocular lens explants. J Cataract Refract Surg 2020; 46: 20-26
• 13 Fernandez-Buenaga R, Alio JL. Intraocular Lens Explantation After Cataract Surgery: Indications, Results, and Explantation Techniques. Asia Pac J Ophthalmol (Phila) 2017; 6: 372-380
• 14 Leysen I, Bartholomeeusen E, Coeckelbergh T. et al. Surgical outcomes of intraocular lens exchange: five-year study. J Cataract Refract Surg 2009; 35: 1013-1018
• 15 Yildirim TM, Khoramnia R, Schickhardt SK. et al. Variation in intraocular lens calcification under different environmental conditions in eyes with supplementary sulcus-supported lenses. Am J Ophthalmol Case Rep 2020; 19: 100797
• 16 Khoramnia R, Salgado JP, Auffarth GU. et al. [Opacification of a hydrophilic intraocular lens 4 years after cataract surgery. A biomaterial analysis]. Ophthalmologe 2012; 109: 483-486
• 17 Tandogan T, Khoramnia R, Choi CY. et al. Optical and material analysis of opacified hydrophilic intraocular lenses after explantation: a laboratory study. BMC Ophthalmol 2015; 15: 170
• 18 Werner L, Apple DJ, Escobar-Gomez M. et al. Postoperative deposition of calcium on the surfaces of a hydrogel intraocular lens. Ophthalmology 2000; 107: 2179-2185
• 19 Khoramnia R, Yildirim TM, Labuz G. et al. [Opacification of intraocular lenses: laboratory and clinical findings]. Ophthalmologe 2021; 118: 633-642
• 20 Schrittenlocher S, Penier M, Schaub F. et al. Intraocular Lens Calcifications After (Triple-) Descemet Membrane Endothelial Keratoplasty. Am J Ophthalmol 2017; 179: 129-136
• 21 Marcovich AL, Tandogan T, Bareket M. et al. Opacification of hydrophilic intraocular lenses associated with vitrectomy and injection of intraocular gas. BMJ Open Ophthalmol 2018; 3: e000157
• 22 Mulisch M, Welsch U. Romeis – Mikroskopische Technik. Heidelberg: Springer Spektrum Berlin, Heidelberg;; 2015
• 23 Gartaganis SP, Kanellopoulou DG, Mela EK. et al. Opacification of hydrophilic acrylic intraocular lens attributable to calcification: investigation on mechanism. Am J Ophthalmol 2008; 146: 395-403
• 24 Buchen SY, Cunanan CM, Gwon A. et al. Assessing intraocular lens calcification in an animal model. J Cataract Refract Surg 2001; 27: 1473-1484
• 25 Britz L, Schickhardt SK, Yildirim TM. et al. Development of a standardized in vitro model to reproduce hydrophilic acrylic intraocular lens calcification. Sci Rep 2022; 12: 7685
• 26 Britz L, Schickhardt SK, Yildirim TM. et al. [Hydrophobic surface properties of hydrophilic acrylic lenses do not protect against calcification]. Ophthalmologie 2023;
• 27 Abdalla Elsayed MEA, Ahmad K, Al-Abdullah AA. et al. Incidence of Intraocular Lens Exchange after Cataract Surgery. Sci Rep 2019; 9: 12877
• 28 Kristianslund O, Raen M, Ostern AE. et al. Late In-the-Bag Intraocular Lens Dislocation: A Randomized Clinical Trial Comparing Lens Repositioning and Lens Exchange. Ophthalmology 2017; 124: 151-159
• 29 Hayashi K, Hirata A, Hayashi H. Possible predisposing factors for in-the-bag and out-of-the-bag intraocular lens dislocation and outcomes of intraocular lens exchange surgery. Ophthalmology 2007; 114: 969-975
• 30 Dalby M, Kristianslund O, Drolsum L. Long-Term Outcomes after Surgery for Late In-The-Bag Intraocular Lens Dislocation: A Randomized Clinical Trial. Am J Ophthalmol 2019; 207: 184-194
• 31 Fernandez-Buenaga R, Alio JL, Perez-Ardoy AL. et al. Late in-the-bag intraocular lens dislocation requiring explantation: risk factors and outcomes. Eye (Lond) 2013; 27: 795-801
• 32 Kristianslund O, Dalby M, Drolsum L. Late in-the-bag intraocular lens dislocation. J Cataract Refract Surg 2021; 47: 942-954
• 33 Lyle WA, Jin JC. An analysis of intraocular lens exchange. Ophthalmic Surg 1992; 23: 453-458
• 34 Balasubramaniam C, Goodfellow J, Price N. et al. Opacification of the Hydroview H60 M intraocular lens: total patient recall. J Cataract Refract Surg 2006; 32: 944-948
• 35 Neuhann IM, Kleinmann G, Apple DJ. A new classification of calcification of intraocular lenses. Ophthalmology 2008; 115: 73-79
• 36 Sher JH, Gooi P, Dubinski W. et al. Comparison of the incidence of opacification of Hydroview hydrogel intraocular lenses with the ophthalmic viscosurgical device used during surgery. J Cataract Refract Surg 2008; 34: 459-464
• 37 Werner L. Causes of intraocular lens opacification or discoloration. J Cataract Refract Surg 2007; 33: 713-726
• 38 Lin SY, Chen KH, Li MJ. et al. Evidence of octacalcium phosphate and type-B carbonated apatites deposited on the surface of explanted acrylic hydrogel intraocular lens. J Biomed Mater Res B Appl Biomater 2004; 70: 203-208
• 39 Costa JF, Bompastor-Ramos P, Marques M. et al. Large-scale opacification of a hydrophilic/hydrophobic intraocular lens. Eur J Ophthalmol 2020; 30: 307-314
• 40 Oculentis. Field Safety Notice: Recall Lentis foldable Intraocular lenses. 2017-09-12. Im Internet (Stand: 10.05.2023): https://www.bfarm.de/SharedDocs/Kundeninfos/EN/11/2017/09163-17_kundeninfo_en.pdf?__blob=publicationFile&v=1
• 41 Scherer NCD, Müller K, Prahs PM. et al. Serial opacification of a hydrophilic-hydrophobic acrylic intraocular lens: analysis of potential risk factors. J Cataract Refract Surg 2020; 46: 1624-1629
• 42 Kim CJ, Choi SK. Analysis of aqueous humor calcium and phosphate from cataract eyes with and without diabetes mellitus. Korean J Ophthalmol 2007; 21: 90-94
• 43 Fung SS, Sykakis E, Islam NM. et al. Intraocular Lens Opacification following Intracameral Injection of Recombinant Tissue Plasminogen Activator to Treat Inflammatory Membranes after Cataract Surgery. J Ophthalmol 2015; 2015: 975075
• 44 Darcy K, Apel A, Donaldson M. et al. Calcification of hydrophilic acrylic intraocular lenses following secondary surgical procedures in the anterior and posterior segments. Br J Ophthalmol 2019; 103: 1700-1703
• 45 Roland S, Khoramnia R, Auffarth GU. et al. [Opacification of hydrophilic intraocular lens after multiple injections of bevacizumab]. Ophthalmologe 2019; 116: 882-886
• 46 Giers BC, Khoramnia R, Tandogan T. et al. [Liquefied Aftercataract Mimicking IOL-Opacification]. Klin Monbl Augenheilkd 2017; 234: 988-990
• 47 Dagres E, Khan MA, Kyle GM. et al. Perioperative complications of intraocular lens exchange in patients with opacified Aqua-Sense lenses. J Cataract Refract Surg 2004; 30: 2569-2573
• 48 Dey A, Bomans PH, Müller FA. et al. The role of prenucleation clusters in surface-induced calcium phosphate crystallization. Nat Mater 2010; 9: 1010-1014
• 49 Kimura K, Kamitakahara M, Yokoi T. et al. Formation Process of Hydroxyapatite Granules in Agarose Hydrogel by Electrophoresis. Cryst Growth Des 2018; 18: 1961-1966
• 50 Fernandez J, Sanchez-Garcia A, Rodriguez-Vallejo M. et al. Systematic review of potential causes of intraocular lens opacification. Clin Exp Ophthalmol 2020; 48: 89-97
• 51 Johnson III JR, Meng l Wnek GE. et al. Electrophoretic calcium phosphate mineralization of collagen hydrogels. Green Materials 2015; 3: 71-79
• 52 Watanabe J, Akashi M. Novel biomineralization for hydrogels: electrophoresis approach accelerates hydroxyapatite formation in hydrogels. Biomacromolecules 2006; 7: 3008-3011
• 53 Zainuddin. Hill DJT, Whittaker AK. et al. Preferential interactions of calcium ions in poly(2-hydroxyethyl methacrylate) hydrogels. J Mater Sci Mater Med 2007; 18: 1141-1149
• 54 Dalas E, Kallitsis JK, Koutsoukos PG. Crystallization of Hydroxyapatite on Polymers. Langmuir 1991; 7: 1822-1826