Choosing Intra Ocular Lens-1 : Material
Choosing the right intra ocular lens (IOL) for cataract surgery is never an easy job. Infact there may be no one IOL that has all the right features embedded in it to match the physiologic functions of the natural lens. Each IOL company seems to focus on a particular set of features, and impress that is what going to matter most for patients. Herein lies the importance of understanding IOLs in detail, and which category of lenses are more suited for which group of patients.
The characteristics and features of all IOLs can be broadly clubbed into the following heads - material, design, optics and delivery. Every feature of the IOL can be categorised under these four broad sections. Each of these sections lead to a particular benefit. All the features of an IOL that will fall under material will lead to one benefit - giving the patient a clear capsule (capsular bag) post operatively with minimal or no opacification of the optic in the years to come. The features of IOL that can be clubbed under design should help the doctor to achieve greater refractive predictability, including rotational stability in case of toric IOLs. Similarly the features that can be bucketed under optics and delivery should provide benefits of better image quality with less dysphotopsia and safe, uncomplicated IOL implantation, respectively. A broad categorisation of IOL features under these sections help in choosing the right IOL for your patients for cataract surgery.
Let us look into the first section- material. As said earlier the benefit of IOL material lies in minimal complication after cataract surgery and provide pristine optics. The most common complication of cataract surgery is posterior capsular opacification (PCO). Though incidence of PCO is much lower with acrylic lenses than with PMMA, popular a few decades back, it still remains one of the most important complication. PCO and ACO (anterior capsular opacification) can together be clubbed as post operative capsular opacification.
When the human crystalline lens is intact, the epithelium of the natural crystalline lens consists of a sheet of anterior epithelial cells that are in continuity with the cells of the equatorial lens bow. The latter cells comprise the germinal cells (reproductive cells) that undergo mitosis (cell division) as they peel off from the equator. They constantly form new lens fibers during normal lens growth. Although both the anterior and equatorial lens epithelial cells (LECs) stem from a continuous cell line and remain in continuity it is useful to divide these into two functional groups. They differ in terms of growth pattern, function and pathologic process after the cataract surgery and IOL implantation.
The anterior or A cells when disturbed, tend to remain in place and not migrate. They are prone to a transformation into fibrous like tissue (pseudofibrous metaplasia, that is differentiating from one cell type to another). In contrast the equaltorical cells migrate towards the posterior capsule. Sometimes they form a fibrotic transformation, but generally they tend to form large balloon like bladder cells- the cells of Wedl, also known as Elschnig pearls. These are the cell types involved in the different forms of postoperative opacification of the capsular bag.
PCO is largely an wound healing response and is characterized by proliferation, differentiation and migration of lens epithelial cells. Residual cells in an attempt to reform the lens starts the process of proliferation. Differentiation may be referred to an Epithelial to Mesenchymal Transition (EMT). When the human capsular bag is intact, the epithelial cells are highly organized and cell to cell polarized thus forming distinct and tight junctions. Post cataract surgery cytokines and chemokines may kick start the process of cell differentiation into mesenchymal cells (thereby loosing their polarity and shape) which then migrate towards the posterior capsule and take the form of fibrosis and pearl or soap water bubble like appearance. Extracellular matrix (ECM) deposition and fibroblast to myofibroblast shaped cells are observed. Fibroblasts play a key role in ECM production, but after surgery capsular wrinkling and fibrosis may be the result of the transition from fibroblasts to myofibroblast.
Post operative capsular opacification involving both posterior and anterior capsule is not related to IOL material alone. David Apple had proposed six factors for the reduction of PCO - three IOL related, and three surgeon related. Assuming the surgeon has done an in the bag implantation with thorough I/A and cortex removal with a continuous curvilinear capsulorhexis of not less than 1 mm of from the IOL optic size, the three IOL related factors that would contribute to less PCO are :
Capsular Biocompatible material
Square edge design optics
Posterior optic of IOL adhesion to posterior capsule
With hydrophobic acrylic IOLs mostly understood to have high capsular biocompatibility, and most IOLs haveing a square edged design today, the bulk of discussion and attention is centred on how the IOL optic can be made to adhere to the posterior capsule. This is the most noticeable feature of the AcrySof, and the adhesion of the posterior optic of the IOL to the posterior capsule has been largely considered to have prevented the migration of equatorial lens cells towards the posterior optic. One aspect of the AcrySof optic that has favoured such adhesion is its sticky optic. However, the stickiness has also often led to adhesion of the haptics on the IOL optic taking a handshaking shape while implantation of the IOL.
Some companies have deliberately incorporated chemical changes on the posterior optic of their IOL to promote more fibronectin binding. The Vivinex (HOYA Surgical Optics) has a special active oxygen treatment on the posterior optic to enhance fibronectin bonding to promote what could be regarded as a sandwich effect, long described by Reijo Linola(1).
The square edge design is incorporated in most lenses worldwide. A reason why it may be the least talked subject today. But recent papers like Nanavaty et al(2) show us that the square edge profile of all lenses are not the same and the sharpness of the square edge profile greatly differed. The hydrophillic lenses in general have a poorer square edge design profile than the hydrophobic IOLs, a possible reason being the square edge profile are compromised as these IOLs are lathe cut in a dehydrated state and then rehydrated. It has been now generally accepted that IOLs that have a square edge profile of less than 10 micron radius of curvature may have a better PCO prevention profile(2). Thus the question is not about square edge, but how square is the squared edge of the IOL?
Apart from the three IOL related facotors listed by David Apple, recently three more aspects of the IOL material are brought to attention. These are:
Smoothness/roughness of the IOL optic
Water contact angle
Tanaka et al (3), postulated that surface roughness might influence the adhesion of cells on the acrylic IOL surface. They experimented with acrylic IOLs of varying surface roughness and found out a direct relation with lens epithelial cell adhesion. The relationship between the roughness value and the meann number of cells that adhered to the IOL surface was studied using an unpolished IOL, and IOL that was polished for 5 hours, and an IOL that was polished for 72 hours. The average roughness value of the surface of each IOL was measured using a 3-dimensional imaging surface structure analyzer (3). Statistically significant differences in cell adhesion were found in this study directly co related to the degree of surface polishing of these IOLs
Water contact angle is another measurement of biocompatibility of the IOL material. Contact angle is the measurement of the angle of contact between a small drop of liquid with the IOL surface. The greater the spread of the liquid on the IOL optic, smaller the contact angle and more hydrophillic property the IOL surface has. Tanaka et al (3) found out more cell adhesion to IOL optic, where the contact angle is low. The term 'wettability' is also often used to describe the contact angle property of an IOL. Lower the contact angle, more the wettability. Therefore a low wettability is associated with high contact angle with the IOL surface, signifying less spreading of the liquid on to the IOL surface, and a more hydophobic surface of the IOL. In their study, Chiara De Giacinto, Daniele Tognetto, et al found varing degree of surface smoothness and contact angle properties of different IOLs (4).
Surface polarity of the IOL is another area which may have an effect on IOL cell migration. It is postulated that lenses that have a negative charge may encounter calcification problem (5). There needs to be more detailed study to find any conclusive evidence between post operative capsular opacification and surface polarity of IOL.
Apart from PCO, the subject of glistening has also been of discussion when it comes to IOL material. Glistening is described as fluid filled micro vacuoles in the IOL matrix that results from deposition of aqueus or BSS in the voids or gaps in the IOL. As IOLs are placed in the bag and sit in an aqueous medium, some of the aqueous may be absorbed within the IOL matrix before the IOL reach its equilibrium state.The absorbed water is usually not visible because it is present in the form of water vapor within the polymer network. However, if water vapor detaches from its surrounding matter, gathering into a void within the polymer network (phase separation), the result is the formation of a visible water drop.
Though many studies have revealed that glistenings may not impact visual acuity, questions on its impact on contrast sensitivity, especially in glare condition remain. This is because, some in vitro studies like Weindler (2009 JCRS), Guenec et al, Xi et al, have indicated a drop in Modulation Transfer Function (MTF) values at high spatial frequencies in terms of cycles per degree of vision (to know more about MTF please refer https://www.quickguide.org/post/modulation-transfer-function-mtf ).
Stray light or disability glare corresponds to a veil of luminance on the retina, that reduces contrast sensitivity which is the result of forward scattering of light on to the retina. Back scattering happens when light thrown into the eye scatters back at the observer. Back scattering of light may not directly effect visual acuity, unless and until there is severe back scattering. On the other hand, patient's contrast sensitivity may drop with forward scattering of light on to the retina. Forward scattering of light may be defined as light that deviates by more than 2.5 degrees from the chief rays of light that reach the fovea. Glistening with disability glare or stray light may increase forward scattering of light creating a veil of luminance on the retina. Machines like the C-Quant stray light meter helps to quantify such stray light on to the retina. Stray light and contrast sensitivity are co related in the sense that more the stray light ( disability glare ), more the drop in contrast sensitivity.
To address the issue of glistening and sub surface nano glistenings (SSNGs) with hydrophobic IOLs, new age IOLs are often being introduced with a slightly more water content, example, the Clareon (ALCON), enVista (B&L), etc.
Another aspect that is also important to discuss is the issue of uveal biocompatibility. Just like capsular biocompatibility of an IOL is indicated by its PCO and ACO characteristics, uveal biocompatibility of an IOL can be studied by the uveal reaction to the IOL post implantation.
Uveitis following cataract surgery and IOL implantation increases the risk of secondary glaucoma following inflammation, cystoid macular edema, and posterior synechiae. Small pigmented deposits on the IOL surface is not necessarily worrisome but larger deposits resembling giant cells are usually a sign of persistent uveitis even if no inflammatory cells in the aqueous is detected. Sometimes such deposits may become a fine anterior pupillary membrane that compromises vision and requires low power YAG membranotomy. In the body’s response to the presence of a foreign body like IOL, monocytes lymphocytes and macrophages migrate through blood vessels to aqueous humor and eventually to the IOL surface. They start a process of phagocytosis in an attempt to remove bacteria and other debris from the IOL surface. As this occur the monocytes and macrophages transform into small round cells and later into giant cells leading to fibrotic activities (Formenak & co-authors 2002). The giant cells may later degenerate and form an acellular proteinaceous membrane on the IOL surface. This can severely raise IOP by increasing inflammation. It is important to study an IOL's uveal biocompatibility and thus determine if it could be implanted in patient's having a weak blood aqueous barrier (BAB).
Hydrphillic IOLs were demonstrated to have a superior uveal biocompatibility in a study in 2002 (6). However, in a 2011 published study by same authors, no remarkable difference was found in cell adhesion between hydorphobic, hydrophillic IOLs and Cee On PMMA lenses 6 months after surgery in control eyes. However, statistically significant difference was found in foreign body giant cells in a renowned hydrophobic IOL group compared to the hydrophillic H lens group who had prior uveitis before cataract surgery. Rauz and co authors, as well as Samuelson and co authors also have described similar amount of giant cells in hydrophobic lens in challenging eyes. In their study, Walid Barbour et al (10) demonstrated a slower macrophage reaction on the hydrophillic lens (Hydroview) than with the a renowned hydrophobic IOL . They postulated that BAB ( blood aqueus barrier) defect and IOL material (hydrophillic, PMMA or hydrophobic) are determinant factors for giant cell deposits post surgery.
Last in this article, I would touch the subject of explantation of IOL. In their research on reasons for explantation of IOL, Neuhann et al reported an analysis of over 200 intra ocular lenses at the JCRS 2020(11). They reported explantation due to opacification of 153 IOLs, followed by explantation of 24 IOLs due to dislocation. Most IOLs that were reported for explantation due to opacification were however due to calcification involving the hydrophillic IOLs. The primary lens that were explanted happened to be Oculentis (119 IOLs) due to late primary calcification. IOL calcification is a concern involving mainly hydrophilic lenses and to some extent Silicone IOLs. The most explanted IOL material happened to be the hydrophillic IOLs with an hydrophobic surface as per the study.
David J Apple had proposed classification of calcification into primary and secondary types. According to him, primary calcification arises due to the IOL itself. The origin of primary calcification may be traced to the nature of the IOL polymer itself (hydrophillic IOLs are more susceptible to calcification) or in its packaging and storage. Secondary calcification was described to have its cause in environmental factors. Incidence of uncontrolled diabetes, BAB (blood aqueus barrier) defect during surgery, pars plana vitrectomy, or other systemic comorbidities may influence secondary calcification. In their study Neuhann et al noted primary calcification majorly with Oculentis. Other explantations of IOLs due to calcification was associated with secondary type.
The two most commonly implanted IOL material are the hydrophobic and hydrophillic IOLs. While the hydrophobic IOLs score high on capsular biocompatibility minimal incidence of IOL opacification due to primary calcification, hydrophillic IOLs have been generally regarded to be associated with less incidence of giant cell deposits and glistening. That being said, more improved versions of hydrophobic IOLs however are reported to have less glistening and better uveal biocompatibility. In next sections on design, optics and delivery, we will focus on other aspects of an IOL features and how it contributes to potential patient benefits.
Sandwich theory: bioactivity-based explanation for posterior capsule opacification, Reijo Linnola, J Cataract Refract Surg 1997 Dec;23(10):1539-42. doi: 10.1016/s0886-3350(97)80026-0
Edge profile of commercially available square-edged intraocular lenses, Mayank Nanavaty, et al https://doi.org/10.1016/j.jcrs.2018.12.004;
Cell adhesion to acrylic intraocular lens associated with lens surface properties, Takao Tanaka,MD et al, JCRS 2005, doi:10.1016/j.jcrs.2004.11.050
4. Surface properties of commercially available hydrophobic acrylic intraocular lenses: Comparative study Chiara De Giacinto, MD, Daniele Tognetto, MD, etal, https://doi.org/10.1016/j.jcrs.2019.04.011
5. Topgraphy, Wettability, and Electrostatic charge consist major surface properties of
Intra Ocular Lenses, Na Yang, et al,
6. Abela-Formanek C, Amon M, Schild G, Schauersberger J, Heinze G, Kruger A. Uveal and capsular biocompatibility of hydrophilic acrylic, hydrophobic acrylic, and silicone intraocular lenses. J Cataract Refract Surg. 2002;28:50–61.
7. Abela-Formanek C, Amon M, Kahraman G, Schauersberger J, Dunavoelgyi R. Biocompatibility of hydrophilic acrylic, hydrophobic acrylic, and silicone intraocular lenses in eyes with uveitis having cataract surgery: Long-term follow-up. J Cataract Refract Surg. 2011;37:104–112.
8. Rauz S, Stavrou P, Murray PI. Evaluation of foldableintraocular lenses in patients with uveitis. Ophthalmology 2000; 107:909–919.
9. Samuelson TW, Chu YR, Kreiger RA. Evaluation of giant-cell deposits on foldable intraocular lenses after combined cataract and glaucoma surgery. J Cataract Refract
Surg 2000; 26:817–823
10. Biological Compatibility of Polymethyl Methacrylate, Hydrophilic Acrylic and Hydrophobic Acrylic Intraocular Lenses Walid Barbour Shizuya Saika Takeshi Miyamoto Yoshitaka Ohnishi, Ophthalmic Res 2005;37:255–261
11. Reasons for explantation, demographics,and material analysis of 200 intraocular
lens explants Tabitha Neuhann, MD, Timur M. Yildirim, MD, Hyeck-Soo Son, MD, Patrick R. Merz, PhD,Ramin Khoramnia, MD, PhD, Gerd U. Auffarth, MD, PhD, J Cataract Refract Surg 2020; 46:20–26
12. Uveal and capsular biocompatibility of hydrophilic acrylic, hydrophobic acrylic, and silicone intraocular lenses Claudette Abela-Formanek January 2002Journal of Cataract and Refractive Surgery 28(1):50-61