- Email: [email protected]
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Safiyya Yousaf1, Saeed Heidari Keshel2, Gholam Ali Farzi3, Majid Momeni-Moghadam4, Ehsaneh Daghigh Ahmadi5, Masoud Mozafari6,7,9, Farshid Sefat1,3,4,8 1Department of Biomedical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, United Kingdom; 2Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Materials and polymer Engineering, Hakim Sabzevari University, Sabzevar, Iran; 4Department of Biology, Faculty of Sciences, Hakim Sabzevari University, Sabzevar, Iran; 5College of Engineering, Institute of Life Science-2, Centre of Nanohealth, Swansea University, Singleton Park, Swansea, United Kingdom; 6Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran; 7Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; 8Interdisciplinary Research Centre in Polymer Science and Technology (IRC Polymer), University of Bradford, Bradford, United Kingdom; 9Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran
61.1 Introduction Transparent, unique, delicate, and highly functional is the lens, containing highly organized cells that alter shape by the contraction and relaxation of the ciliary muscle to assist focus on objects at varying distances. The integrity of the corneal posterior is indispensable for the formation of a clear image. Cataract compromises eye sight and increases degradation of optical clarity due to clouding and lens opacification (Fig. 61.1). Change in structure and organization of characterized lens fibers increases light scattering dramatically, reducing lens performance [1]. The primary objective of cataract surgery is translated by restoring vision and substantially regaining interaction with the surroundings to improve patients’ quality of life with considerable gains in social and emotional life [2]. The ideal goal for achieving full refractive correction relies on implantation of intraocular lenses (IOLs) to replace the eye’s native lens. The evolution of these IOLs has stimulated pioneers to progress with phacoemulsification devices and operative techniques with increasingly smaller incisions. The technique offers promising outcomes with advanced performance capabilities and tailored rehabilitation for individual lifestyle needs such as reading and driving. Previous expectations of cataract surgery-induced improvements no longer consider the need for thick spectacle lenses rather to optimize modern psychometric methods.
Handbook of Tissue Engineering Scaffolds: Volume Two. https://doi.org/10.1016/B978-0-08-102561-1.00028-2 Copyright © 2019 Elsevier Ltd. All rights reserved.
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Eye with healthy lens
Eye with cataract Retina
Healthy lens
Light is focused sharply, producing clear images
Lens with cataract
Light is scattered by a cloudy lens causing “foggy’’ images
Figure 61.1 A schematic diagram to present the effects of cataract.
Figure 61.2 A schematic diagram of the first invented intraocular lens (IOL) implanted by Ridley in 1949. The design had very little in common with current IOLs used today as it was associated with many complications.
61.2 History of intraocular lens The unique apodized design of the IOL was serendipitously discovered by Sir Harold Ridley, tracing his first surgery to November 29, 1949 (Fig. 61.2). Ridley concurred and overcame the concern of rejection when shattered aircraft windscreens penetrated the eyes of injured pilots during combat in World War II. He noticed splinters of the acrylic plastic had no obvious signs of refusal, consequently, proposed the use of artificial lenses. Ridley implanted the first polymethylmethacrylate (PMMA) IOL using the extracapsular technique on a 45-year-old woman suffering from unilateral cataracts. Unequivocally, this manifested the beginning of an era in ophthalmological
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Figure 61.3 A schematic drawing of the first foldable intraocular lens, necessary for phacoemulsification despite being free from complications and causing intense reaction in some eyes.
development to uncover optical correction and perseverance against the complications with eye surgery [63]. Summarizing the modifications, in 1952, cataract surgery had evolved from its earliest form to a Ridley-Rayner lens. Determined to reduce the incidence of complications and provide superior visual rehabilitation, Ridley and Peter Choyce worked closely to accelerate the pace toward generating a medical-industrial complex [3]. Although history views Ridley’s work as a pivotal epoch, his benefitting discovery between 1948 and the 1980s was supported by few yet defamed by many. Following a campaign, phacoemulsification eventually became a variation for the removal of cataracts, regardless of the majority of eye surgeons classifying the method as an “experimental” technique [4]. Not until the late 1970 and 1980s did he begin to receive appropriate praise and gratitude for his momentous invention (Apple and Sims, 1996). Thomas Mazzocco’s concept of foldable silicone lenses culminated in lens implantations, induced through a small incision, essential for phacoemulsification. He discovered postoperative recovery with a 3-mm incision would enhance wound stability, accelerate visual recovery, and reduce the incidence of astigmatism as a larger incision weakens the meridian involved. The first commercially available IOL platform displayed remarkable ophthalmic establishment in research, which led the design to be rapidly adopted worldwide. In essence, one of the drawbacks of early foldable IOLs was the adverse reactions experienced in some eyes and complications with decentration (Fig. 61.3). The indication of major research accomplishments led to opportunities for modern medicine to enhance properties and design options.
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61.3 The need for intraocular lenses The lens is a significantly organized system of cells with a biconvex, transparent semisolid body. A high refractive index is maintained precisely by aligned zonular fibers with minimal intercellular spaces [5]. This fulfills the dominating function of altering the amount of light entering the eye to focus on the retina. The presence of an elastic lens capsule accommodates for the change in shape and varies its focal point under the influence of the ciliary muscle. Alternating between a distant to a near object can result in a tension decrease allowing the lens to become rounder and thicker [6]. As part of the native aging process, the lens diminishes its competence to change shape, hence, a spectacle lens is generally required to hasten visual acuity of near objects.
61.3.1 Cataracts Cataract is the leading cause of blindness and visual impairment worldwide by the opacification of the human lens [7,8]. An increase in light scattering and light absorption destroys the structure of characterized lens fibers by the accumulation of metabolic products [64]. Disturbance of osmotic balance between the aqueous humor and lens contributes to one of the many factors that causes cataract. The incidence of the disease increases with age (around 50) as a result of enlarged lens and a rise of insoluble proteins [67] (Fig. 61.4). Age-related cataracts can be divided into three categories: cortical, nuclear, and posterior subcapsular cataracts. Cortical cataracts originate at the cortex and extend to the central region of the lens, whereas posterior subcapsular cataracts develop a plaque-like opacity in the axial posterior cortical layer [7]. Poor general health, diabetes mellitus, a lower socioeconomic status, smoking, the consumption of alcohol, and occupational exposure to cataractogenic agents are all $QWHULRUFDSVXOH 1XFOHXV
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Figure 61.4 A schematic view of lens structures and corresponding types of cataract.
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exponential and contributing factors. The current treatment for cataract is the surgical removal of the native lens to be replaced with a permanent artificial IOL. The outcome permits adequate and independent visual acuity using a small incision to the cornea. Preoperative assessment and management is necessary to enable selection of the correct lens power to attain focus on near and distant objects [7].
61.4 Currently used intraocular lenses Irrespective of the IOL category, ophthalmic surgery with the advent of phacoemulsification appears to consequent rapid visual and physical rehabilitation. There are three various types of incisions for phacoemulsification: • Standard incisions: 2.75–3.2 mm diameter incisions • Mini incision: incisions for phacoemulsification reduced to 2.2 mm • Micro incisions: incisions less than or equal to 1.8 mm diameter.
The gradual improvement of ocular therapeutics has led to foldable IOLs to gain considerable attention based on their ability to return to their original shape with no apparent abnormalities. Soft lenses and the loading of folded IOLs into narrow tunnels of injectors strengthen protection for the corneal endothelium. Foldable lenses characterize flexibility that facilitate easier explantation particularly due to less perilenticular fibrosis that leads to early mobilization in the capsule bag [4].
61.5 Types of intraocular lenses 61.5.1 Monofocal intraocular lenses Monofocal IOLs appear to remain the most popular type of IOL to replace the focusing power of the natural lens. They assist favorable properties including good visual quality, adequate contrast sensitivity, easy power calculation, and low cost. Despite their excellent distance acuity, patients who undergo cataract extraction require a reading in addition to their prescription for near and intermediate vision [9]. The initial distinction of monofocal IOLs is grounded on their design: three piece or single piece. Moreover, they can be classified on the basis of their presence or absence of asphericity, optic shape, and material composition used in production or the shape of haptics.
61.5.2 One-piece and three-piece intraocular lenses Following the success of technological advancements in IOLs and insertion systems, a desire for less invasive surgery has steered the use of increasingly smaller incisions. Researchers have withdrawn the option of one-piece lenses simply due to potential damage caused during the folding process. With regard to refractive characteristics, lens stability, incidence of tilt, and percentage opacification of the posterior capsule and the anterior capsule opening, one-piece IOLs are identical to three-piece IOLs [10].
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The philosophy applied to three-piece IOLs varies slightly between manufacturing companies, i.e., length of haptics, color, and dimension [4].
61.5.3 Toric intraocular lenses Toric IOLs have been a major evolutionary sequel in the development of IOL for monochromatic and chromatic abbreviation corrections. A recent metaanalysis reported that these lenses have established to deliver better uncorrected visual acuity, a reduced amount of residual astigmatism, and a heightened spectacle independence when compared with that of nontoric lenses [11]. Astigmatism is referred to as a refractive error reducing visual acuity through the meridian defocus (Fig. 61.5). Even when minimal, astigmatism can lead to distorted vision, glare, eye strain, and increase prevalence of headaches. Reducing preexisting astigmatism may further improve visual comfort and postoperative outcomes. Several techniques can apply to eliminate astigmatism including selective positioning of the phacoemulsification incision, corneal relaxing incisions, and excimer laser keratectomy [12]. In spite of these methods, the denouement is not always promising including the degree of which the condition can be treated due to age, incision number, magnitude, width, depth, and shape [66].
61.5.4 Multifocal intraocular lenses Multifocal IOLs (MFIOLs) possess interesting results for the correction of presbyopia in cataract patients who undergo surgery. They perform a different depth of focus capabilities in which multiple focal lengths appear within the optical zone. Recent models focus on using a nonphysiological optical method to improve bifocality along with intermediate vision to guarantee spectacle and contact lens independence. MFIOLs, by definition, divide light into varying foci, changing the vision’s physiology due to light dispersion when entering the eye [13–16]. MFIOLs are available in two designs with the intention of assisting good unaided distance and near vision based on multifocal properties: refractive and diffractive [17]. A common limitation of refractive MFIOLs is their loss of energy and pupil dependence [65]. These models
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Figure 61.6 Schematic diagram of (a) refractive intraocular lenses showing how light disperses at different refractive annular zones and (b) diffractive intraocular lenses showing the diffraction of light by the concentric zones at varying distances This division of light may occur to different focuses by far and intermediate vision as they are highly dependant on pupic dynamics. As reduction in contrast sensitivity can cause halos and glare, newer designs include a continuous change in curvature between zones, allowing sufficient vision throughout.
reach multifocality and are reliant on pupil dynamics by different refractive power annular zones. Despite the postoperatory success in many patients, complications and visual symptoms may affect the patient’s level of satisfaction—potential for halos and glare increased sensitivity for lens centration and reduced contrast sensitivity. With diffractive lenses embracing their visual performance, the division of light may occur at a combination of two or more varying anterior spherical surfaces. Composed of diffractive microstructures, the diffractive models contain concentric zones that become adjacent as they distance from the center point [18] (Fig. 61.6).
61.5.5 Drug-loaded intraocular lenses Because inflammation of the eye may arise after cataract surgery, IOLs loaded with antibiotics have anticipated an alternative to both conventional injections and eye drops. Drug delivery is proposed to initiate at the target site to fight against bacterial proliferation and reduce posterior chamber opacification. The drug has been tested in various regions: (1) embedded within the IOL itself, (2) in a coating applied onto the IOL, and (3) in a disparate reservoir attached to the IOL. Albeit, research in this area remains in its prime; thus, the drug-loaded IOLs have not reached at a stage to become commercially available nor to undergo clinical trials.
61.6 Materials The eye is complex and unique among all organs in that it has large volumes which are completely avascular [19]. These avascular tissues are inherently isolated from the body’s immune response, making the eye an excellent candidate for mimicking
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the native lens by the fabrication of a permanent prosthesis to restore optical quality. In recent years, cataract surgery has escalated rapidly and accounts for over 47% of blindness worldwide [20–22]. Therefore, it necessitates phacoemulsification, which is the process of terminating lens architecture for cells to be aspirated and combined with an IOL implantation. The replacement of an opacified lens remains one of the most common surgical procedures performed to correct refractive complications. The evolution of optical plastics for ophthalmic application has been a growing research aspect for material scientists worldwide. With dramatic progression of lens design, properties, and modalities of wear, current focus remains on optimizing comfort and ensuring satisfactory lens performance. IOLs entail a number of contradictory functions for multiple purposes, i.e., restoring vision and understanding the mechanical interplay of native tissues to allow biomimetic hydrogels to be studied and examined for suitable IOL fabrication. Several factors come into play when selecting the material and design to ensure pleasing clinical outcomes and postoperative results. Despite advances in research, difficulties persist with posterior capsule opacification (PCO), which is caused by the immune response and various suppositions including the separation of the posterior capsule from the anterior capsule [22].
61.6.1 Biocompatibility Biocompatibility is a term used to describe the capability of an implanted prosthesis to exist in harmony with surrounding tissues [23]. Uveal biocompatibility refers to how well an IOL is tolerated inside the eye without causing deleterious changes and immunogenic responses. Other ways of defining biocompatibility include capsular biocompatibility, which is determined by the direct contact with the lens capsular bag and remnant lens epithelial cells. This interaction may consequence various entities including anterior capsule opacification, PCO, and lens epithelial cell ingrowth. Moreover, the aforementioned parameters assessed are fairly different between capsular and uveal biocompatibility as a particular IOL may exhibit poor capsular biocompatibility yet characterize minimal foreign body reactions on the surface of the lens. Therefore, the potential to calcify should always be taken into consideration when evaluating materials for ultimate biocompatibility after implantation [24–26].
61.6.2 Optical performance From an ophthalmic standpoint, the ultimate goal of an artificial lens is to deliver optical power in conjunction with the cornea to focus light onto the retina. The phenomenon of IOL properties displays great prominence to understanding their optical performance and function on implantation. The prime purpose of an IOL is to improve weakened vision, correct refraction, and permit optimal visual rehabilitation. The main chemical constituents of commercial IOLs currently present today are divided into three material categories: hydrophobic acrylics, hydrophilic acrylics (or hydrogels), and hydrophobic silicone elastomers.
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61.6.3 Polymethylmethacrylate With the introduction of the earliest IOLs, PMMA is strongly recognized for its longterm stability, excellent light transmission properties, and ability to sufficiently tolerate the eye on implantation [27]. Additionally, PMMA is considered to be very inert, amorphous, and transparent providing minimal inflammatory responses. It is a polymer of methacrylate, encouraging cell adhesion, good centration, and resistance to tilt. With regard to PMMA, its optical portions can be produced by one of two methods: grinding and molding. Grinding enables thick blocks of PMMA to be thinned either by a rotating blade circulating the block of PMMA or cutting of the PMMA block while it rotates in a support. To achieve a smooth surface, the lens is then polished. Injection molding has become a viable manufacturing practise for precision optics. The widespread use of this process involves the following: 1. Heat the PMMA to approximately 160–200°C until it liquefies. 2. Inject the liquid PMMA into a mold cavity allowing the desired shape to be produced. 3. Formerly fill the cavity and maintain the pressure. 4. Once cooled, release the mold. 5. Polish the desired shape.
Compression molding is a high volume, high pressure method of molding PMMA to produce a much tougher material with enhanced mechanical properties. The technique involves preheating PMMA in an open mold cavity to be closed and compressed under a pressure of approximately 500 kg/cm2. Following the preformed desired composite, the mold is heated to 20°C with an increased pressure of 2600 kg/cm2. The pressure is then returned to normal values, and the mold is cooled with air [4].
61.6.4 Silicone Silicone IOLs have acquired a reputation for the use in cataract surgery since their appearance in 1984 [28]. Silicone is a polymer of polyorganosiloxane with a biomedical platform used in the elastomeric form for ophthalmic application. The silicone IOL implantation technique indorses momentous delicacy due to poor resistance of the lens material. Although silicone polymers have been developed with even higher refractive indices, intraocular unfolding has become extremely rapid, almost explosive and impossible to control. Therefore, in the past decade, there has been a continuous decline in the fabrication of silicone IOLs, despite its PCO blocking effect. Numerous direct, comparative studies have examined the polymer and revealed potential downsides. Additionally, they have been suspected to facilitate bacterial adhesion leading to an increased risk of postoperative complications [29]. These lenses are also problematic to manipulate when wet as the silicone becomes slippery. Moreover, the exposure of a silicone interface when there is a possibility of vitreoretinal surgery can interfere with the visual assessment of the retina and result in serious visual disturbances. The aforementioned reasons indicate why silicone IOLs are being abandoned and are not the preferred material choice for the majority of surgeons [4,30].
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61.6.5 Hydrophobic foldable acrylic Hydrophobic acrylic materials consist of a series of copolymers: acrylate and methacrylate derived from rigid PMMA. Relatively inert and flexible, they verify the suitability for the haptics of a monobloc open-loop IOL [31]. Their physical properties substantiate excellent capsular biocompatibility, resistance, and ability to be folded at room temperature regaining their original shape [32]. Hydrophobic acrylic IOLs are extremely thin, moderately easy to implant, and are available in three-piece or one-piece designs. Hydrophobic IOLs have rose to prominence primarily on the basis of their good mechanical stability and durability. Moreover, during the postoperative period, they elicit a low incidence of PCO. Another common feature involves a low tendency to self-centre during surgery, therefore demands accurate positioning. Unfortunately, one of the drawbacks of hydrophobic IOLs has been reported to cause dysphotopsias more frequently than any other type of acrylic IOL predominantly due to a high refractive index. The formation of small water inclusions referred to as glistening can occur within the IOL optics accumulating overtime in hydrophobic materials [33]. Despite the edge glare, dysphotopsia has considerably reduced with the introduction of new and established models that are prehydrated to equilibrium, rejecting additional water, thus avoiding the development of glistenings [30].
61.6.6 Hydrophilic acrylic Hydrophilic acrylic belongs to a fairly heterogeneous material group constituting a mixture of poly-HEMA and a hydrophilic acrylic monomer [34]. Hydrophilic acrylic lenses are cut in the dehydrated state and when stored hydrated in solution. Giving rise to a list of various copolymers, in the late 1980s, IOLs endured numerous modifications. The current quantity of water generally varies between 18% and 38% with a contact angle below 50 degrees. Hydrophilic acrylic material has commendable biocompatibility (due to its hydrophilic surface), is relatively easy to handle, and is less liable to receive abrasions or injury from operative instruments. They have a low surface energy, soft flexible exterior, somewhat compressible, and implanted via a 2-mm opening, close to no alteration during handling and folding procedures necessary for elementary insertion. Nonetheless, during the postoperative period, the development tendency of photopsias is low, whereas the PCO rate is considered to be much greater than in other materials (hydrophobic acrylic lenses or silicone lenses) [35]. This is potentially due to an elevated water content attracting cell proliferation on the lens and poor resistance to capsular bag contraction [36]. Inducing a less sharp bend on the optic edge similar to hydrophobic materials can possibly mitigate the ingrowth of lens epithelial cells [37]. Moreover, hydrophilic acrylic materials deliberate weaker properties than hydrophobic materials as they are unable to anticipate high contraction forces. A major concern relies with optic opacification between various companies as the formation of calcium deposits have led to IOL exchange in numeral patients due to declining of visual quality [38–40]. Notwithstanding the evidence of calcification, hydrophilic lenses are extensively used in Europe simply for their ease of implantation and amended outcomes with PCO [30] (Fig. 61.7).
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Figure 61.7 A representation of the anteriorly elevated intraocular lens (IOL) that is cut along its longitudinal axis using scissors. (a). Rotated at 180 degrees, a second cut is made to eventually form two pieces of the IOL. (b) The corrective IOL is located, and the incision is sealed by sutures or hydrating the corneal stroma. Used by permission from P. Narang, R. Steinert, B. Little, A. Agarwal, Intraocular lens scaffold to facilitate intraocular lens exchange, J Cataract Refract Surg 40 (9) (2014) 1403–1407.
61.7 Complications Efforts to constrain surgical complications remain a common focus in the use of IOLs. A successful implantation does not always result in an optimal outcome. Unfortunately, there are numerous technical phenomena that can lead to compromised sight and refractive errors. Therefore, to reduce the incidence of impediments to the design, manufacturing techniques and surgical procedures hold great prominence in ophthalmic research. The ultimate goal relies on restoring vision to simultaneously give patients the ability of spectacle independence. Clinically, IOL complication can be divided into intraoperative, early postoperative, and late postoperative.
61.7.1 Posterior capsule opacification PCO is a common complication of cataract surgery, thus, the most frequent reason for patient dissatisfaction following an IOL implantation [41–43] (Fig. 61.8). Modern day cataract extraction procedures comprise a capsular bag which constitutes a portion of the anterior and the entire posterior capsule. The bag separates the aqueous humor from the vitreous humor and predominantly houses the IOL. The presence of resilient epithelial cells begins to stubbornly reside and recolonize the denuded regions of the anterior capsule. These cells then proliferate, migrate, and transform into myofibroblasts occupying the regions of the space between the posterior capsule and the IOL. Forming swollen globular cells known as Elschnig’s pearls, the cells continue to divide and ultimately encroach on the visual axis, altering the matrix and exponentially mitigating visual acuity [68].
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Figure 61.8 A schematic drawing to represent (a) the postsurgical capsular bag and (b) the extensive growth and effect of posterior capsule opacification.
Nd:YAG laser capsulotomy is the best treatment to resolve secondary opacity of the capsule [15,44]. The major drawback involves the chance of developing other complications as the risk of an IOL exchange is multiplied following a previous posterior capsulotomy. Therefore, surgeons are encouraged to reserve the procedure until all levels of patient dissatisfaction are treated or discarded [41,43]. Imperative management and maximum attention is necessary to regulate laser power as errors may give rise to secondary visual loss and generate microcracks in the lens optic. Moreover, many efforts are made on modifying lens design, biomaterials, and surgical equipment to prevent the development of PCO [22].
61.7.2 Bacterial adhesion Bacterial adhesion during cataract extraction or IOL implantation is a prominent etiological factor in the pathogenesis of infectious endophthalmitis. Following adhesion, bacteria tends to replicate, congregate, and manifest numerous layers of microcolonies. It is enriched by the development of polysaccharide biofilms which vary according to the nature of the surroundings: hydrophobicity or hydrophilicity of the biomaterial [45]. Thus, it tends to adhere by electrostatic charge from physical forces and is embedded in a layer of slime. In many cases, the microorganisms originate from periocular flora [46] and enter via surgical instruments, the irrigation fluid [47], or by the contaminated prosthesis itself. Postoperative endophthalmitis entails sight-threatening complications with common characteristics of deteriorated vision, lid swelling, pain, and accumulated pus in the anterior chamber of the eye. A therapeutic level of antibiotics delivered by systemic or local administration during IOL implantation can potentially mitigate bacterial proliferation [48].
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61.7.3 Dry eyes Dry eyes are a multifactorial disease of the lacrimal film resulting in symptoms of discomfort, tear film instability, visual disturbance, and potential damage to the ocular surface. The condition is accompanied by a significant increase in osmolality of the lacrimal film and inflammation of the cornea [49]. Nevertheless, patients with dry eyes must be treated before surgery as symptoms may aggravate following implantation of an IOL. In essence, it is essential to consider the volume of the lacrimal meniscus and to inspect the Meibomian glands for any dysfunctions that can potentially be responsible for lacking the lipid component [4]. Excessive evaporation will induce deteriorated visual quality, blurred vision, and intensify foreign body sensation [50,62].
61.7.4 Malposition/decentration of the intraocular lens Errors with IOL positioning compromise the quality of vision depending on the degree of decentration, IOL design, and the pupil size. This optical complication can occur following capsular rupture or when the haptics enter the region of absent zonular fibers, thus slide into the vitreous causing disruption to the IOL. Malpositioning may account for the original lens extraction, or progress postoperatively due to internal and external forces. Internal forces implicate a size disparity between the site of fixation and the IOL, scarring and capsular contraction. External forces comprise trauma and eye rubbing. Visual acuity correlates with misalignment, therefore, if misplaced, the IOL loses its ability to accomplish optimal properties [4,15,51].
61.8 Future of intraocular lenses Refinement and modifications of surgical techniques for cataract surgery have become the research front in the 21st century. The ability to restore vision and aid optical rehabilitation with an IOL remains controversy as patient’s desire of spectacle independence continues to rise. In spite of the common drawbacks, the incidence of IOL complications has mitigated by a reduction in the corneal incision size. The development of new biomaterials, biotechnology, and IOL type has led to improved postoperative outcomes [52]. The demand for extraordinary mechanical properties assists extra functionalities in traditional IOLs to maximize safety and efficiency [53]. Several aspects are fundamental for determining the clinical excellence and effectiveness of IOLs. Future IOL generations focus on premium IOL designs that ensure sufficient long-term uveal and capsular biocompatibility. The status of measurement methods for innovative IOL calculation devices acquires fast, precise, and predictable results to further improve postoperative visual results. Undoubtedly, patients still experience some form of dissatisfaction despite the careful selection and screening [54]; therefore, adequate management of long-term prevention is always better than cure. The occurrence of PCO is defectively an issue that requires profound study and research to address methods of overcoming operative or postoperative complications.
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Light-adjustable IOLs function by correcting the remaining refractive errors following cataract surgery. Appropriate light intensity patterns are used to irradiate the IOLs allowing the correction of defocus and astigmatism [55]. With developing lightadjusting mechanisms and digital light delivery devices, the future for IOLs seems promising with high success rates [56] Hence, the next generation of IOLs intend to incorporate UV and blue-light adsorbing properties to avoid potential harmful effects and photochemical damage to the retina [53,57,58]. Therefore, the evolution of manifest refraction and visual acuity remains an ongoing focus for ophthalmologists to optimize sight restoration after cataract surgery and despite all criticism to be commercially available [59,60].
61.9 Summary Today, Ridley’s genius invention has undoubtedly benefited multiple people worldwide. The gradual improvement of IOL development has evolved from rigid materials to foldable agents, reducing the incidence of complications between each generation. The demand for enhanced biocompatibility remains one of the major trends of material advancement. Optical quality relies on successful quality control to ensure the integrity of visual comfort, rehabilitation performance, dimensional tolerances, and enhanced mechanical properties. IOL use is no longer restricted to cataract surgery but also to improve refractive outcomes in accordance with the evolution of IOL design. Research remains ongoing to offer satisfaction to both the surgeon delivering this complex procedure and the patients who hope to acquire long-lasting vision and refractive stability.
References [1] N. Chong, Clinical Ocular Physiology: An Introductory Text, Butterworth-Heinemann, Oxford, 1996. [2] E. Lamoureux, E. Fenwick, K. Pesudovs, D. Tan, The impact of cataract surgery on quality of life, Curr Opin Ophthalmol 22 (1) (2011) 19–27. [3] H. Sarwar, N. Modi, Sir Harold Ridley: innovator of cataract surgery, J Perioperat Pract 24 (9) (2014) 210–212. [4] L. Buratto, S. Brint, D. Boccuzzi, Cataract Surgery and Intraocular Lenses, SLACK Incorporated, 2014. [5] J.M. Tiffany, cited in: S.E. Skalicky (2016) Ocular and Visial Physiology (2008). [6] J.E. Dowling, J.L. Dowling, Vision: How it Works and What Can Go Wrong, The MIT Press, Cambridge, Massachusetts, 2016. [7] D. Lam, S. Rao, V. Ratra, Y. Liu, P. Mitchell, J. King, Cataract, Nat Rev Dis Prim 1 (15014) (2015). [8] L. Remón, S. García-Delpech, P. Udaondo, V. Ferrando, J. Monsoriu, W. Furlan, Fractalstructured multifocal intraocular lens, PLoS One 13 (7) (2018). [9] S. de Silva, J. Evans, V. Kirthi, M. Ziaei, M. Leyland, Multifocal versus monofocal intraocular lenses after cataract extraction, Cochrane Database Syst Rev 12 (2016). Art. No.: CD003169. https://doi.org/10.1002/14651858.CD003169.pub4.
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[10] R. Nejima, A prospective, randomised comparison of single and three-piece acrylic foldable intraocular lenses, Br J Ophthalmol 88 (6) (2004) 746–749. [11] L. Kessel, J. Andresen, B. Tendal, D. Erngaard, P. Flesner, J. Hjortdal, Toric intraocular lenses in the correction of astigmatism during cataract surgery, Ophthalmology 123 (2) (2016) 275–286. [12] J. Mendicute, C. Irigoyen, J. Aramberri, A. Ondarra, R. Montés-Micó, Foldable toric intraocular lens for astigmatism correction in cataract patients, J Cataract Refract Surg 34 (4) (2008) 601–607. [13] J. Alfonso, L. Fernández-Vega, M. Baamonde, R. Montés-Micó, Prospective visual evaluation of apodized diffractive intraocular lenses, J Cataract Refract Surg 33 (7) (2007) 1235–1243. [14] J. Alió, B. Elkady, D. Ortiz, G. Bernabeu, Microincision multifocal intraocular lens with and without a capsular tension ring, J Cataract Refract Surg 34 (9) (2008) 1468–1475. [15] J. Alio, A. Plaza-Puche, R. Férnandez-Buenaga, J. Pikkel, M. Maldonado, Multifocal intraocular lenses: an overview, Surv Ophthalmol 62 (5) (2017) 611–634. [16] J. Artigas, J. Menezo, C. Peris, A. Felipe, M. Díaz-Llopis, Image quality with multifocal intraocular lenses and the effect of pupil size, J Cataract Refract Surg 33 (12) (2007) 2111–2117. [17] M. Leyland, E. Zinicola, Multifocal versus monofocal intraocular lenses in cataract surgery, Ophthalmology 110 (9) (2003) 1789–1798. [18] J. Alió, L. Salerno, M. Tiveron, Multifocal intraocular lenses: types, outcomes, complications and how to solve them, Taiwan J Ophthalmol 7 (4) (2017) 179. [19] M. Reilly, K. Swindle-Reilly, N. Ravi, Hydrogels for intraocular lenses and other ophthalmic prostheses, Biomed Hydrogels (2011) 118–148. [20] D. Allen, Cataract, BMJ Clin Evid (2011). [21] D. Allen, A. Vasavada, Cataract and surgery for cataract, BMJ 333 (7559) (2006) 128–132. [22] B. Wang, Q. Lin, C. Shen, J. Tang, Y. Han, H. Chen, Hydrophobic modification of polymethyl methacrylate as intraocular lenses material to improve the cytocompatibility, J Colloid Interface Sci 431 (2014) 1–7. [23] E. Becker, S. Landau, A. Manuila, International Dictionary of Medicine and Biology, Churchill Livingstone, New York, 1986. [24] N. Mamalis, Intraocular lens biocompatibility, J Cataract Refract Surg 28 (1) (2002) 1–2. [25] M. Roesel, C. Heinz, B. Heimes, J. Koch, A. Heiligenhaus, Uveal and capsular biocompatibility of two foldable acrylic intraocular lenses in patients with endogenous uveitis — a prospective randomized study, Graefe’s Arch Clin Exp Ophthalmol 246 (11) (2008) 1609–1615. [26] L. Werner, Biocompatibility of intraocular lens materials, Curr Opin Ophthalmol 19 (1) (2008) 41–49. [27] O. Findl, W. Buehl, R. Menapace, S. Sacu, M. Georgopoulos, G. Rainer, Long-term effect of sharp optic edges of a polymethyl methacrylate intraocular lens on posterior capsule opacification, Ophthalmology 112 (11) (2005) 2004–2008. [28] T.R. Mazzocco, G.M. Rajacich, E. Epstein, Soft Implant Lenses in Cataract Surgery, Slack, Thorofare, 1986. [29] S. Baillif, R. Ecochard, D. Hartmann, J. Freney, L. Kodjikian, Intraocular lens and cataract surgery: comparison between bacterial adhesion and risk of postoperative endophthalmitis according to intraocular lens biomaterial, J Fr Ophtalmol 32 (2009) 515–528. [30] R. Bellucci, An introduction to intraocular lenses: material, optics, haptics, design and aberration, Cataract (2013) 38–55. [31] C.M. Cunanan, M. Ghazizadeh, S.Y. Buchen, P.M. Knight, Contact-angle analysis of intraocular lenses, J Cataract Refract Surg 24 (1998) 341–351.
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[32] T. Oshika, Y. Shiokawa, Effect of folding on the optical quality of soft acrylic intraocular lenses, J Cataract Refract Surg 22 (1996) 1360–1364. [33] M.A. Farbowitz, N.A. Zabriskie, A.S. Crandall, et al., Visual complaints associated with the AcrySof acrylic intraocular lens, J Cataract Refract Surg 26 (9) (2000) 1339–1345. [34] M. Chehade, M.J. Elder, Intraocular lens materials and styles: a review, Aust N Z J Ophthalmol 25 (1997) 255–263. [35] O. Findl, C. Leydolt, Meta-analysis of accommodating intraocular lenses, J Cataract Refract Surg 33 (3) (2007) 522–527. [36] H.V. Gimbel, G.P. Condon, T. Kohnen, R.J. Olson, I. Halkiadakis, Late in-the-bag intraocular lens dislocation: incidence, prevention, and management, J Cataract Refract Surg 31 (2005) 2193–2204. [37] M.A. Nanavaty, D.J. Spalton, J. Boyce, et al., Edge profile of commercially available square-edged intraocular lenses, J Cataract Refract Surg 34 (4) (2008) 677–686. [38] A. Frohn, H.B. Dick, A.J. Augustin, F.H. Grus, Late opacification of the foldable hydrophilic acrylic lens SC60B-OUV, Ophthalmology 108 (11) (2001) 1999–2004. [39] N.E. Habib, T.J. Freegard, G. Gock, et al., Late surface opacification of Hydroview intraocular lenses, Eye 16 (1) (2002) 69–74. [40] J.M. Schmidbauer, L. Werner, D.J. Apple, et al., Postoperative opacification of posterior chamber intraocular lenses—a review, Klin Monatsbl Augenheilkd 218 (9) (2001) 586–594. [41] J.L. Alio, A.B. Plaza-Puche, J. Javaloy, M.J. Ayala, L.J. Moreno, D.P. Piñero, Comparison of a new refractive multifocal intraocular lens with an inferior segmental near add and a diffractive multifocal intraocular lens, Ophthalmology 119 (3) (2012) 555–563. [42] V. Maurino, B.D. Allan, G.S. Rubin, C. Bunce, W. Xing, O. Findl, Moorfields IOL Study Group, Quality of vision after bilateral multifocal intraocular lens implantation: a randomized trial – AT LISA 809M versus AcrySof ReSTOR SN6AD1, Ophthalmology 122 (4) (2015) 700–710. [43] E. Rosen, J.L. Alió, H.B. Dick, S. Dell, S. Slade, Efficacy and safety of multifocal intraocular lenses following cataract and refractive lens exchange: metaanalysis of peer-reviewed publications, J Cataract Refract Surg 42 (2) (2016) 310–328. [44] O. Findl, W. Buehl, P. Bauer, T. Sycha, Interventions for preventing posterior capsule opacification, Cochrane Database Syst Rev (2010). [45] J.W.B. Bainbridge, M. Teimory, H. Tabandeh, et al., Intraocular lens implants and risk of endophthalmitis, Br J Ophthalmol 82 (1998) 1312–1315. [46] M. Speaker, F. Milch, M. Shah, W. Eisner, B. Kreiswirth, Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis, Ophthalmology 98 (5) (1991) 639–650. [47] D.R. Sherwood, W.J. Rich, J.S. Jacob, et al., Bacterial contamination of intraocular and extraocular fluids during extracapsular cataract extraction, Eye 3 (1989) 308–312. [48] T. Liesegang, Prophylactic antibiotics in cataract operations, Mayo Clin Proc 72 (2) (1997) 149–159. [49] C. Chan, Dry Eye, Springer, New York, 2015, pp. 2–9. [50] J. Alio, J. Colecha, S. Pastor, A. Rodriguez, A. Artola, Symptomatic dry eye treatment with autologous platelet-rich plasma, Ophthalmic Res 39 (3) (2007) 124–129. [51] A. Carlson, W. Stewart, P. Tso, Intraocular lens complications requiring removal or exchange, Surv Ophthalmol 42 (5) (1998) 417–440. [52] P. Peña-Garcia, L.A. Jorge, M.L. Raúl, Multifocal Intraocular Lenses: The Art and the Practice 21, 2014.
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[53] J. Zvorničanin, E. Zvorničanin, Premium intraocular lenses: the past, present and future, J Curr Ophthalmol 30 (4) (2018) 287–296. [54] R. Braga-Mele, D. Chang, S. Dewey, G. Foster, B. Henderson, W. Hill, R. Hoffman, B. Little, N. Mamalis, T. Oetting, D. Serafano, A. Talley-Rostov, A. Vasavada, S. Yoo, Multifocal intraocular lenses: relative indications and contraindications for implantation, J Cataract Refract Surg 40 (2) (2014) 313–322. [55] D.M. Schwartz, Light-adjustable lens, Trans Am Ophthalmol Soc 101 (2003) 417–436. [56] J. Ford, L. Werner, N. Mamalis, Adjustable intraocular lens power technology, J Cataract Refract Surg 40 (7) (2014) 1205–1223. [57] A.R. Young, Acute effects of UVR on human eyes and skin, Prog Biophys Mol Biol 92 (1) (2006) 80–85. [58] J.A. Zuclich, Ultraviolet induced damage in the primate cornea and retina, Curr Eye Res 3 (1) (1984) 27–34 62. [59] E. Villegas, E. Alcon, E. Rubio, J. Marín, P. Artal, Refractive accuracy with light-adjustable intraocular lenses, J Cataract Refract Surg 40 (7) (2014) 1075.e2–1084.e2. [60] N. Yu, F. Fang, B. Wu, L. Zeng, Y. Cheng, State of the art of intraocular lens manufacturing, Int J Adv Manuf Technol 98 (5–8) (2018) 1103–1130. [61] P. Narang, R. Steinert, B. Little, A. Agarwal, Intraocular lens scaffold to facilitate intraocular lens exchange, J Cataract Refract Surg 40 (9) (2014) 1403–1407. [62] J. Alio, A. Abdelghany, R. Fernández-Buenaga, Management of residual refractive error after cataract surgery, Current Opinion in Ophthalmology 25 (4) (2014) 291–297. [63] D. Apple, J. Sims, Harold Ridley and the invention of the intraocular lens, Survey of Ophthalmology 40 (4) (1996) 279–292. [64] J.D. Bartlett, S.D. Jaanus, Clinical Ocular Pharmacology, 4th ed., Butterworth Heinemann, 2001. [65] A. Dyrda, A. Martínez-Palmer, D. Martín-Moral, A. Rey, A. Morilla, M. Castilla-Martí, J. Aronés-Santivañez, Clinical Results of Diffractive, Refractive, Hybrid Multifocal, and Monofocal Intraocular Lenses, Journal of Ophthalmology (2018) 1–12. [66] R.M. Kershner, Keratolenticuloplasty: Arcuate keratotomy for cataract surgery and astigmatism, JCRS Volume 21 (3) (1995) 274–277. https://doi.org/10.1016/ S0886-3350(13)80131-9. [67] R.S. Snell, M.A. Lemp, Clinical Anatomy of the Eye, Second edition, Blackwell Publishing, Oxford, 1998. [68] I. Wormstone, L. Wang, C. Liu, Posterior capsule opacification, Experimental Eye Research 88 (2) (2009) 257–269.
Further reading [1] Y. Liu, M. Wilkins, T. Kim, B. Malyugin, J. Mehta, Cataracts, Lancet 390 (10094) (2017) 600–612. [2] I. Wormstone, L. Wang, C. Liu, Posterior capsule opacification, Exp Eye Res 88 (2) (2009) 257–269.
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Safiyya Yousaf1, Saeed Heidari Keshel2, Gholam Ali Farzi3, Majid Momeni-Moghadam4, Ehsaneh Daghigh Ahmadi5, Masoud Mozafari6,7,9, Farshid Sefat1,3,4,8 1Department of Biomedical and Electronics Engineering, School of Engineering, University of Bradford, Bradford, United Kingdom; 2Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Materials and polymer Engineering, Hakim Sabzevari University, Sabzevar, Iran; 4Department of Biology, Faculty of Sciences, Hakim Sabzevari University, Sabzevar, Iran; 5College of Engineering, Institute of Life Science-2, Centre of Nanohealth, Swansea University, Singleton Park, Swansea, United Kingdom; 6Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran; 7Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; 8Interdisciplinary Research Centre in Polymer Science and Technology (IRC Polymer), University of Bradford, Bradford, United Kingdom; 9Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran
61.1 Introduction Transparent, unique, delicate, and highly functional is the lens, containing highly organized cells that alter shape by the contraction and relaxation of the ciliary muscle to assist focus on objects at varying distances. The integrity of the corneal posterior is indispensable for the formation of a clear image. Cataract compromises eye sight and increases degradation of optical clarity due to clouding and lens opacification (Fig. 61.1). Change in structure and organization of characterized lens fibers increases light scattering dramatically, reducing lens performance [1]. The primary objective of cataract surgery is translated by restoring vision and substantially regaining interaction with the surroundings to improve patients’ quality of life with considerable gains in social and emotional life [2]. The ideal goal for achieving full refractive correction relies on implantation of intraocular lenses (IOLs) to replace the eye’s native lens. The evolution of these IOLs has stimulated pioneers to progress with phacoemulsification devices and operative techniques with increasingly smaller incisions. The technique offers promising outcomes with advanced performance capabilities and tailored rehabilitation for individual lifestyle needs such as reading and driving. Previous expectations of cataract surgery-induced improvements no longer consider the need for thick spectacle lenses rather to optimize modern psychometric methods.
Handbook of Tissue Engineering Scaffolds: Volume Two. https://doi.org/10.1016/B978-0-08-102561-1.00028-2 Copyright © 2019 Elsevier Ltd. All rights reserved.
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Eye with healthy lens
Eye with cataract Retina
Healthy lens
Light is focused sharply, producing clear images
Lens with cataract
Light is scattered by a cloudy lens causing “foggy’’ images
Figure 61.1 A schematic diagram to present the effects of cataract.
Figure 61.2 A schematic diagram of the first invented intraocular lens (IOL) implanted by Ridley in 1949. The design had very little in common with current IOLs used today as it was associated with many complications.
61.2 History of intraocular lens The unique apodized design of the IOL was serendipitously discovered by Sir Harold Ridley, tracing his first surgery to November 29, 1949 (Fig. 61.2). Ridley concurred and overcame the concern of rejection when shattered aircraft windscreens penetrated the eyes of injured pilots during combat in World War II. He noticed splinters of the acrylic plastic had no obvious signs of refusal, consequently, proposed the use of artificial lenses. Ridley implanted the first polymethylmethacrylate (PMMA) IOL using the extracapsular technique on a 45-year-old woman suffering from unilateral cataracts. Unequivocally, this manifested the beginning of an era in ophthalmological
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Figure 61.3 A schematic drawing of the first foldable intraocular lens, necessary for phacoemulsification despite being free from complications and causing intense reaction in some eyes.
development to uncover optical correction and perseverance against the complications with eye surgery [63]. Summarizing the modifications, in 1952, cataract surgery had evolved from its earliest form to a Ridley-Rayner lens. Determined to reduce the incidence of complications and provide superior visual rehabilitation, Ridley and Peter Choyce worked closely to accelerate the pace toward generating a medical-industrial complex [3]. Although history views Ridley’s work as a pivotal epoch, his benefitting discovery between 1948 and the 1980s was supported by few yet defamed by many. Following a campaign, phacoemulsification eventually became a variation for the removal of cataracts, regardless of the majority of eye surgeons classifying the method as an “experimental” technique [4]. Not until the late 1970 and 1980s did he begin to receive appropriate praise and gratitude for his momentous invention (Apple and Sims, 1996). Thomas Mazzocco’s concept of foldable silicone lenses culminated in lens implantations, induced through a small incision, essential for phacoemulsification. He discovered postoperative recovery with a 3-mm incision would enhance wound stability, accelerate visual recovery, and reduce the incidence of astigmatism as a larger incision weakens the meridian involved. The first commercially available IOL platform displayed remarkable ophthalmic establishment in research, which led the design to be rapidly adopted worldwide. In essence, one of the drawbacks of early foldable IOLs was the adverse reactions experienced in some eyes and complications with decentration (Fig. 61.3). The indication of major research accomplishments led to opportunities for modern medicine to enhance properties and design options.
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61.3 The need for intraocular lenses The lens is a significantly organized system of cells with a biconvex, transparent semisolid body. A high refractive index is maintained precisely by aligned zonular fibers with minimal intercellular spaces [5]. This fulfills the dominating function of altering the amount of light entering the eye to focus on the retina. The presence of an elastic lens capsule accommodates for the change in shape and varies its focal point under the influence of the ciliary muscle. Alternating between a distant to a near object can result in a tension decrease allowing the lens to become rounder and thicker [6]. As part of the native aging process, the lens diminishes its competence to change shape, hence, a spectacle lens is generally required to hasten visual acuity of near objects.
61.3.1 Cataracts Cataract is the leading cause of blindness and visual impairment worldwide by the opacification of the human lens [7,8]. An increase in light scattering and light absorption destroys the structure of characterized lens fibers by the accumulation of metabolic products [64]. Disturbance of osmotic balance between the aqueous humor and lens contributes to one of the many factors that causes cataract. The incidence of the disease increases with age (around 50) as a result of enlarged lens and a rise of insoluble proteins [67] (Fig. 61.4). Age-related cataracts can be divided into three categories: cortical, nuclear, and posterior subcapsular cataracts. Cortical cataracts originate at the cortex and extend to the central region of the lens, whereas posterior subcapsular cataracts develop a plaque-like opacity in the axial posterior cortical layer [7]. Poor general health, diabetes mellitus, a lower socioeconomic status, smoking, the consumption of alcohol, and occupational exposure to cataractogenic agents are all $QWHULRUFDSVXOH 1XFOHXV
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exponential and contributing factors. The current treatment for cataract is the surgical removal of the native lens to be replaced with a permanent artificial IOL. The outcome permits adequate and independent visual acuity using a small incision to the cornea. Preoperative assessment and management is necessary to enable selection of the correct lens power to attain focus on near and distant objects [7].
61.4 Currently used intraocular lenses Irrespective of the IOL category, ophthalmic surgery with the advent of phacoemulsification appears to consequent rapid visual and physical rehabilitation. There are three various types of incisions for phacoemulsification: • Standard incisions: 2.75–3.2 mm diameter incisions • Mini incision: incisions for phacoemulsification reduced to 2.2 mm • Micro incisions: incisions less than or equal to 1.8 mm diameter.
The gradual improvement of ocular therapeutics has led to foldable IOLs to gain considerable attention based on their ability to return to their original shape with no apparent abnormalities. Soft lenses and the loading of folded IOLs into narrow tunnels of injectors strengthen protection for the corneal endothelium. Foldable lenses characterize flexibility that facilitate easier explantation particularly due to less perilenticular fibrosis that leads to early mobilization in the capsule bag [4].
61.5 Types of intraocular lenses 61.5.1 Monofocal intraocular lenses Monofocal IOLs appear to remain the most popular type of IOL to replace the focusing power of the natural lens. They assist favorable properties including good visual quality, adequate contrast sensitivity, easy power calculation, and low cost. Despite their excellent distance acuity, patients who undergo cataract extraction require a reading in addition to their prescription for near and intermediate vision [9]. The initial distinction of monofocal IOLs is grounded on their design: three piece or single piece. Moreover, they can be classified on the basis of their presence or absence of asphericity, optic shape, and material composition used in production or the shape of haptics.
61.5.2 One-piece and three-piece intraocular lenses Following the success of technological advancements in IOLs and insertion systems, a desire for less invasive surgery has steered the use of increasingly smaller incisions. Researchers have withdrawn the option of one-piece lenses simply due to potential damage caused during the folding process. With regard to refractive characteristics, lens stability, incidence of tilt, and percentage opacification of the posterior capsule and the anterior capsule opening, one-piece IOLs are identical to three-piece IOLs [10].
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The philosophy applied to three-piece IOLs varies slightly between manufacturing companies, i.e., length of haptics, color, and dimension [4].
61.5.3 Toric intraocular lenses Toric IOLs have been a major evolutionary sequel in the development of IOL for monochromatic and chromatic abbreviation corrections. A recent metaanalysis reported that these lenses have established to deliver better uncorrected visual acuity, a reduced amount of residual astigmatism, and a heightened spectacle independence when compared with that of nontoric lenses [11]. Astigmatism is referred to as a refractive error reducing visual acuity through the meridian defocus (Fig. 61.5). Even when minimal, astigmatism can lead to distorted vision, glare, eye strain, and increase prevalence of headaches. Reducing preexisting astigmatism may further improve visual comfort and postoperative outcomes. Several techniques can apply to eliminate astigmatism including selective positioning of the phacoemulsification incision, corneal relaxing incisions, and excimer laser keratectomy [12]. In spite of these methods, the denouement is not always promising including the degree of which the condition can be treated due to age, incision number, magnitude, width, depth, and shape [66].
61.5.4 Multifocal intraocular lenses Multifocal IOLs (MFIOLs) possess interesting results for the correction of presbyopia in cataract patients who undergo surgery. They perform a different depth of focus capabilities in which multiple focal lengths appear within the optical zone. Recent models focus on using a nonphysiological optical method to improve bifocality along with intermediate vision to guarantee spectacle and contact lens independence. MFIOLs, by definition, divide light into varying foci, changing the vision’s physiology due to light dispersion when entering the eye [13–16]. MFIOLs are available in two designs with the intention of assisting good unaided distance and near vision based on multifocal properties: refractive and diffractive [17]. A common limitation of refractive MFIOLs is their loss of energy and pupil dependence [65]. These models
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Figure 61.6 Schematic diagram of (a) refractive intraocular lenses showing how light disperses at different refractive annular zones and (b) diffractive intraocular lenses showing the diffraction of light by the concentric zones at varying distances This division of light may occur to different focuses by far and intermediate vision as they are highly dependant on pupic dynamics. As reduction in contrast sensitivity can cause halos and glare, newer designs include a continuous change in curvature between zones, allowing sufficient vision throughout.
reach multifocality and are reliant on pupil dynamics by different refractive power annular zones. Despite the postoperatory success in many patients, complications and visual symptoms may affect the patient’s level of satisfaction—potential for halos and glare increased sensitivity for lens centration and reduced contrast sensitivity. With diffractive lenses embracing their visual performance, the division of light may occur at a combination of two or more varying anterior spherical surfaces. Composed of diffractive microstructures, the diffractive models contain concentric zones that become adjacent as they distance from the center point [18] (Fig. 61.6).
61.5.5 Drug-loaded intraocular lenses Because inflammation of the eye may arise after cataract surgery, IOLs loaded with antibiotics have anticipated an alternative to both conventional injections and eye drops. Drug delivery is proposed to initiate at the target site to fight against bacterial proliferation and reduce posterior chamber opacification. The drug has been tested in various regions: (1) embedded within the IOL itself, (2) in a coating applied onto the IOL, and (3) in a disparate reservoir attached to the IOL. Albeit, research in this area remains in its prime; thus, the drug-loaded IOLs have not reached at a stage to become commercially available nor to undergo clinical trials.
61.6 Materials The eye is complex and unique among all organs in that it has large volumes which are completely avascular [19]. These avascular tissues are inherently isolated from the body’s immune response, making the eye an excellent candidate for mimicking
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the native lens by the fabrication of a permanent prosthesis to restore optical quality. In recent years, cataract surgery has escalated rapidly and accounts for over 47% of blindness worldwide [20–22]. Therefore, it necessitates phacoemulsification, which is the process of terminating lens architecture for cells to be aspirated and combined with an IOL implantation. The replacement of an opacified lens remains one of the most common surgical procedures performed to correct refractive complications. The evolution of optical plastics for ophthalmic application has been a growing research aspect for material scientists worldwide. With dramatic progression of lens design, properties, and modalities of wear, current focus remains on optimizing comfort and ensuring satisfactory lens performance. IOLs entail a number of contradictory functions for multiple purposes, i.e., restoring vision and understanding the mechanical interplay of native tissues to allow biomimetic hydrogels to be studied and examined for suitable IOL fabrication. Several factors come into play when selecting the material and design to ensure pleasing clinical outcomes and postoperative results. Despite advances in research, difficulties persist with posterior capsule opacification (PCO), which is caused by the immune response and various suppositions including the separation of the posterior capsule from the anterior capsule [22].
61.6.1 Biocompatibility Biocompatibility is a term used to describe the capability of an implanted prosthesis to exist in harmony with surrounding tissues [23]. Uveal biocompatibility refers to how well an IOL is tolerated inside the eye without causing deleterious changes and immunogenic responses. Other ways of defining biocompatibility include capsular biocompatibility, which is determined by the direct contact with the lens capsular bag and remnant lens epithelial cells. This interaction may consequence various entities including anterior capsule opacification, PCO, and lens epithelial cell ingrowth. Moreover, the aforementioned parameters assessed are fairly different between capsular and uveal biocompatibility as a particular IOL may exhibit poor capsular biocompatibility yet characterize minimal foreign body reactions on the surface of the lens. Therefore, the potential to calcify should always be taken into consideration when evaluating materials for ultimate biocompatibility after implantation [24–26].
61.6.2 Optical performance From an ophthalmic standpoint, the ultimate goal of an artificial lens is to deliver optical power in conjunction with the cornea to focus light onto the retina. The phenomenon of IOL properties displays great prominence to understanding their optical performance and function on implantation. The prime purpose of an IOL is to improve weakened vision, correct refraction, and permit optimal visual rehabilitation. The main chemical constituents of commercial IOLs currently present today are divided into three material categories: hydrophobic acrylics, hydrophilic acrylics (or hydrogels), and hydrophobic silicone elastomers.
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61.6.3 Polymethylmethacrylate With the introduction of the earliest IOLs, PMMA is strongly recognized for its longterm stability, excellent light transmission properties, and ability to sufficiently tolerate the eye on implantation [27]. Additionally, PMMA is considered to be very inert, amorphous, and transparent providing minimal inflammatory responses. It is a polymer of methacrylate, encouraging cell adhesion, good centration, and resistance to tilt. With regard to PMMA, its optical portions can be produced by one of two methods: grinding and molding. Grinding enables thick blocks of PMMA to be thinned either by a rotating blade circulating the block of PMMA or cutting of the PMMA block while it rotates in a support. To achieve a smooth surface, the lens is then polished. Injection molding has become a viable manufacturing practise for precision optics. The widespread use of this process involves the following: 1. Heat the PMMA to approximately 160–200°C until it liquefies. 2. Inject the liquid PMMA into a mold cavity allowing the desired shape to be produced. 3. Formerly fill the cavity and maintain the pressure. 4. Once cooled, release the mold. 5. Polish the desired shape.
Compression molding is a high volume, high pressure method of molding PMMA to produce a much tougher material with enhanced mechanical properties. The technique involves preheating PMMA in an open mold cavity to be closed and compressed under a pressure of approximately 500 kg/cm2. Following the preformed desired composite, the mold is heated to 20°C with an increased pressure of 2600 kg/cm2. The pressure is then returned to normal values, and the mold is cooled with air [4].
61.6.4 Silicone Silicone IOLs have acquired a reputation for the use in cataract surgery since their appearance in 1984 [28]. Silicone is a polymer of polyorganosiloxane with a biomedical platform used in the elastomeric form for ophthalmic application. The silicone IOL implantation technique indorses momentous delicacy due to poor resistance of the lens material. Although silicone polymers have been developed with even higher refractive indices, intraocular unfolding has become extremely rapid, almost explosive and impossible to control. Therefore, in the past decade, there has been a continuous decline in the fabrication of silicone IOLs, despite its PCO blocking effect. Numerous direct, comparative studies have examined the polymer and revealed potential downsides. Additionally, they have been suspected to facilitate bacterial adhesion leading to an increased risk of postoperative complications [29]. These lenses are also problematic to manipulate when wet as the silicone becomes slippery. Moreover, the exposure of a silicone interface when there is a possibility of vitreoretinal surgery can interfere with the visual assessment of the retina and result in serious visual disturbances. The aforementioned reasons indicate why silicone IOLs are being abandoned and are not the preferred material choice for the majority of surgeons [4,30].
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61.6.5 Hydrophobic foldable acrylic Hydrophobic acrylic materials consist of a series of copolymers: acrylate and methacrylate derived from rigid PMMA. Relatively inert and flexible, they verify the suitability for the haptics of a monobloc open-loop IOL [31]. Their physical properties substantiate excellent capsular biocompatibility, resistance, and ability to be folded at room temperature regaining their original shape [32]. Hydrophobic acrylic IOLs are extremely thin, moderately easy to implant, and are available in three-piece or one-piece designs. Hydrophobic IOLs have rose to prominence primarily on the basis of their good mechanical stability and durability. Moreover, during the postoperative period, they elicit a low incidence of PCO. Another common feature involves a low tendency to self-centre during surgery, therefore demands accurate positioning. Unfortunately, one of the drawbacks of hydrophobic IOLs has been reported to cause dysphotopsias more frequently than any other type of acrylic IOL predominantly due to a high refractive index. The formation of small water inclusions referred to as glistening can occur within the IOL optics accumulating overtime in hydrophobic materials [33]. Despite the edge glare, dysphotopsia has considerably reduced with the introduction of new and established models that are prehydrated to equilibrium, rejecting additional water, thus avoiding the development of glistenings [30].
61.6.6 Hydrophilic acrylic Hydrophilic acrylic belongs to a fairly heterogeneous material group constituting a mixture of poly-HEMA and a hydrophilic acrylic monomer [34]. Hydrophilic acrylic lenses are cut in the dehydrated state and when stored hydrated in solution. Giving rise to a list of various copolymers, in the late 1980s, IOLs endured numerous modifications. The current quantity of water generally varies between 18% and 38% with a contact angle below 50 degrees. Hydrophilic acrylic material has commendable biocompatibility (due to its hydrophilic surface), is relatively easy to handle, and is less liable to receive abrasions or injury from operative instruments. They have a low surface energy, soft flexible exterior, somewhat compressible, and implanted via a 2-mm opening, close to no alteration during handling and folding procedures necessary for elementary insertion. Nonetheless, during the postoperative period, the development tendency of photopsias is low, whereas the PCO rate is considered to be much greater than in other materials (hydrophobic acrylic lenses or silicone lenses) [35]. This is potentially due to an elevated water content attracting cell proliferation on the lens and poor resistance to capsular bag contraction [36]. Inducing a less sharp bend on the optic edge similar to hydrophobic materials can possibly mitigate the ingrowth of lens epithelial cells [37]. Moreover, hydrophilic acrylic materials deliberate weaker properties than hydrophobic materials as they are unable to anticipate high contraction forces. A major concern relies with optic opacification between various companies as the formation of calcium deposits have led to IOL exchange in numeral patients due to declining of visual quality [38–40]. Notwithstanding the evidence of calcification, hydrophilic lenses are extensively used in Europe simply for their ease of implantation and amended outcomes with PCO [30] (Fig. 61.7).
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Figure 61.7 A representation of the anteriorly elevated intraocular lens (IOL) that is cut along its longitudinal axis using scissors. (a). Rotated at 180 degrees, a second cut is made to eventually form two pieces of the IOL. (b) The corrective IOL is located, and the incision is sealed by sutures or hydrating the corneal stroma. Used by permission from P. Narang, R. Steinert, B. Little, A. Agarwal, Intraocular lens scaffold to facilitate intraocular lens exchange, J Cataract Refract Surg 40 (9) (2014) 1403–1407.
61.7 Complications Efforts to constrain surgical complications remain a common focus in the use of IOLs. A successful implantation does not always result in an optimal outcome. Unfortunately, there are numerous technical phenomena that can lead to compromised sight and refractive errors. Therefore, to reduce the incidence of impediments to the design, manufacturing techniques and surgical procedures hold great prominence in ophthalmic research. The ultimate goal relies on restoring vision to simultaneously give patients the ability of spectacle independence. Clinically, IOL complication can be divided into intraoperative, early postoperative, and late postoperative.
61.7.1 Posterior capsule opacification PCO is a common complication of cataract surgery, thus, the most frequent reason for patient dissatisfaction following an IOL implantation [41–43] (Fig. 61.8). Modern day cataract extraction procedures comprise a capsular bag which constitutes a portion of the anterior and the entire posterior capsule. The bag separates the aqueous humor from the vitreous humor and predominantly houses the IOL. The presence of resilient epithelial cells begins to stubbornly reside and recolonize the denuded regions of the anterior capsule. These cells then proliferate, migrate, and transform into myofibroblasts occupying the regions of the space between the posterior capsule and the IOL. Forming swollen globular cells known as Elschnig’s pearls, the cells continue to divide and ultimately encroach on the visual axis, altering the matrix and exponentially mitigating visual acuity [68].
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Figure 61.8 A schematic drawing to represent (a) the postsurgical capsular bag and (b) the extensive growth and effect of posterior capsule opacification.
Nd:YAG laser capsulotomy is the best treatment to resolve secondary opacity of the capsule [15,44]. The major drawback involves the chance of developing other complications as the risk of an IOL exchange is multiplied following a previous posterior capsulotomy. Therefore, surgeons are encouraged to reserve the procedure until all levels of patient dissatisfaction are treated or discarded [41,43]. Imperative management and maximum attention is necessary to regulate laser power as errors may give rise to secondary visual loss and generate microcracks in the lens optic. Moreover, many efforts are made on modifying lens design, biomaterials, and surgical equipment to prevent the development of PCO [22].
61.7.2 Bacterial adhesion Bacterial adhesion during cataract extraction or IOL implantation is a prominent etiological factor in the pathogenesis of infectious endophthalmitis. Following adhesion, bacteria tends to replicate, congregate, and manifest numerous layers of microcolonies. It is enriched by the development of polysaccharide biofilms which vary according to the nature of the surroundings: hydrophobicity or hydrophilicity of the biomaterial [45]. Thus, it tends to adhere by electrostatic charge from physical forces and is embedded in a layer of slime. In many cases, the microorganisms originate from periocular flora [46] and enter via surgical instruments, the irrigation fluid [47], or by the contaminated prosthesis itself. Postoperative endophthalmitis entails sight-threatening complications with common characteristics of deteriorated vision, lid swelling, pain, and accumulated pus in the anterior chamber of the eye. A therapeutic level of antibiotics delivered by systemic or local administration during IOL implantation can potentially mitigate bacterial proliferation [48].
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61.7.3 Dry eyes Dry eyes are a multifactorial disease of the lacrimal film resulting in symptoms of discomfort, tear film instability, visual disturbance, and potential damage to the ocular surface. The condition is accompanied by a significant increase in osmolality of the lacrimal film and inflammation of the cornea [49]. Nevertheless, patients with dry eyes must be treated before surgery as symptoms may aggravate following implantation of an IOL. In essence, it is essential to consider the volume of the lacrimal meniscus and to inspect the Meibomian glands for any dysfunctions that can potentially be responsible for lacking the lipid component [4]. Excessive evaporation will induce deteriorated visual quality, blurred vision, and intensify foreign body sensation [50,62].
61.7.4 Malposition/decentration of the intraocular lens Errors with IOL positioning compromise the quality of vision depending on the degree of decentration, IOL design, and the pupil size. This optical complication can occur following capsular rupture or when the haptics enter the region of absent zonular fibers, thus slide into the vitreous causing disruption to the IOL. Malpositioning may account for the original lens extraction, or progress postoperatively due to internal and external forces. Internal forces implicate a size disparity between the site of fixation and the IOL, scarring and capsular contraction. External forces comprise trauma and eye rubbing. Visual acuity correlates with misalignment, therefore, if misplaced, the IOL loses its ability to accomplish optimal properties [4,15,51].
61.8 Future of intraocular lenses Refinement and modifications of surgical techniques for cataract surgery have become the research front in the 21st century. The ability to restore vision and aid optical rehabilitation with an IOL remains controversy as patient’s desire of spectacle independence continues to rise. In spite of the common drawbacks, the incidence of IOL complications has mitigated by a reduction in the corneal incision size. The development of new biomaterials, biotechnology, and IOL type has led to improved postoperative outcomes [52]. The demand for extraordinary mechanical properties assists extra functionalities in traditional IOLs to maximize safety and efficiency [53]. Several aspects are fundamental for determining the clinical excellence and effectiveness of IOLs. Future IOL generations focus on premium IOL designs that ensure sufficient long-term uveal and capsular biocompatibility. The status of measurement methods for innovative IOL calculation devices acquires fast, precise, and predictable results to further improve postoperative visual results. Undoubtedly, patients still experience some form of dissatisfaction despite the careful selection and screening [54]; therefore, adequate management of long-term prevention is always better than cure. The occurrence of PCO is defectively an issue that requires profound study and research to address methods of overcoming operative or postoperative complications.
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Light-adjustable IOLs function by correcting the remaining refractive errors following cataract surgery. Appropriate light intensity patterns are used to irradiate the IOLs allowing the correction of defocus and astigmatism [55]. With developing lightadjusting mechanisms and digital light delivery devices, the future for IOLs seems promising with high success rates [56] Hence, the next generation of IOLs intend to incorporate UV and blue-light adsorbing properties to avoid potential harmful effects and photochemical damage to the retina [53,57,58]. Therefore, the evolution of manifest refraction and visual acuity remains an ongoing focus for ophthalmologists to optimize sight restoration after cataract surgery and despite all criticism to be commercially available [59,60].
61.9 Summary Today, Ridley’s genius invention has undoubtedly benefited multiple people worldwide. The gradual improvement of IOL development has evolved from rigid materials to foldable agents, reducing the incidence of complications between each generation. The demand for enhanced biocompatibility remains one of the major trends of material advancement. Optical quality relies on successful quality control to ensure the integrity of visual comfort, rehabilitation performance, dimensional tolerances, and enhanced mechanical properties. IOL use is no longer restricted to cataract surgery but also to improve refractive outcomes in accordance with the evolution of IOL design. Research remains ongoing to offer satisfaction to both the surgeon delivering this complex procedure and the patients who hope to acquire long-lasting vision and refractive stability.
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[32] T. Oshika, Y. Shiokawa, Effect of folding on the optical quality of soft acrylic intraocular lenses, J Cataract Refract Surg 22 (1996) 1360–1364. [33] M.A. Farbowitz, N.A. Zabriskie, A.S. Crandall, et al., Visual complaints associated with the AcrySof acrylic intraocular lens, J Cataract Refract Surg 26 (9) (2000) 1339–1345. [34] M. Chehade, M.J. Elder, Intraocular lens materials and styles: a review, Aust N Z J Ophthalmol 25 (1997) 255–263. [35] O. Findl, C. Leydolt, Meta-analysis of accommodating intraocular lenses, J Cataract Refract Surg 33 (3) (2007) 522–527. [36] H.V. Gimbel, G.P. Condon, T. Kohnen, R.J. Olson, I. Halkiadakis, Late in-the-bag intraocular lens dislocation: incidence, prevention, and management, J Cataract Refract Surg 31 (2005) 2193–2204. [37] M.A. Nanavaty, D.J. Spalton, J. Boyce, et al., Edge profile of commercially available square-edged intraocular lenses, J Cataract Refract Surg 34 (4) (2008) 677–686. [38] A. Frohn, H.B. Dick, A.J. Augustin, F.H. Grus, Late opacification of the foldable hydrophilic acrylic lens SC60B-OUV, Ophthalmology 108 (11) (2001) 1999–2004. [39] N.E. Habib, T.J. Freegard, G. Gock, et al., Late surface opacification of Hydroview intraocular lenses, Eye 16 (1) (2002) 69–74. [40] J.M. Schmidbauer, L. Werner, D.J. Apple, et al., Postoperative opacification of posterior chamber intraocular lenses—a review, Klin Monatsbl Augenheilkd 218 (9) (2001) 586–594. [41] J.L. Alio, A.B. Plaza-Puche, J. Javaloy, M.J. Ayala, L.J. Moreno, D.P. Piñero, Comparison of a new refractive multifocal intraocular lens with an inferior segmental near add and a diffractive multifocal intraocular lens, Ophthalmology 119 (3) (2012) 555–563. [42] V. Maurino, B.D. Allan, G.S. Rubin, C. Bunce, W. Xing, O. Findl, Moorfields IOL Study Group, Quality of vision after bilateral multifocal intraocular lens implantation: a randomized trial – AT LISA 809M versus AcrySof ReSTOR SN6AD1, Ophthalmology 122 (4) (2015) 700–710. [43] E. Rosen, J.L. Alió, H.B. Dick, S. Dell, S. Slade, Efficacy and safety of multifocal intraocular lenses following cataract and refractive lens exchange: metaanalysis of peer-reviewed publications, J Cataract Refract Surg 42 (2) (2016) 310–328. [44] O. Findl, W. Buehl, P. Bauer, T. Sycha, Interventions for preventing posterior capsule opacification, Cochrane Database Syst Rev (2010). [45] J.W.B. Bainbridge, M. Teimory, H. Tabandeh, et al., Intraocular lens implants and risk of endophthalmitis, Br J Ophthalmol 82 (1998) 1312–1315. [46] M. Speaker, F. Milch, M. Shah, W. Eisner, B. Kreiswirth, Role of external bacterial flora in the pathogenesis of acute postoperative endophthalmitis, Ophthalmology 98 (5) (1991) 639–650. [47] D.R. Sherwood, W.J. Rich, J.S. Jacob, et al., Bacterial contamination of intraocular and extraocular fluids during extracapsular cataract extraction, Eye 3 (1989) 308–312. [48] T. Liesegang, Prophylactic antibiotics in cataract operations, Mayo Clin Proc 72 (2) (1997) 149–159. [49] C. Chan, Dry Eye, Springer, New York, 2015, pp. 2–9. [50] J. Alio, J. Colecha, S. Pastor, A. Rodriguez, A. Artola, Symptomatic dry eye treatment with autologous platelet-rich plasma, Ophthalmic Res 39 (3) (2007) 124–129. [51] A. Carlson, W. Stewart, P. Tso, Intraocular lens complications requiring removal or exchange, Surv Ophthalmol 42 (5) (1998) 417–440. [52] P. Peña-Garcia, L.A. Jorge, M.L. Raúl, Multifocal Intraocular Lenses: The Art and the Practice 21, 2014.
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[53] J. Zvorničanin, E. Zvorničanin, Premium intraocular lenses: the past, present and future, J Curr Ophthalmol 30 (4) (2018) 287–296. [54] R. Braga-Mele, D. Chang, S. Dewey, G. Foster, B. Henderson, W. Hill, R. Hoffman, B. Little, N. Mamalis, T. Oetting, D. Serafano, A. Talley-Rostov, A. Vasavada, S. Yoo, Multifocal intraocular lenses: relative indications and contraindications for implantation, J Cataract Refract Surg 40 (2) (2014) 313–322. [55] D.M. Schwartz, Light-adjustable lens, Trans Am Ophthalmol Soc 101 (2003) 417–436. [56] J. Ford, L. Werner, N. Mamalis, Adjustable intraocular lens power technology, J Cataract Refract Surg 40 (7) (2014) 1205–1223. [57] A.R. Young, Acute effects of UVR on human eyes and skin, Prog Biophys Mol Biol 92 (1) (2006) 80–85. [58] J.A. Zuclich, Ultraviolet induced damage in the primate cornea and retina, Curr Eye Res 3 (1) (1984) 27–34 62. [59] E. Villegas, E. Alcon, E. Rubio, J. Marín, P. Artal, Refractive accuracy with light-adjustable intraocular lenses, J Cataract Refract Surg 40 (7) (2014) 1075.e2–1084.e2. [60] N. Yu, F. Fang, B. Wu, L. Zeng, Y. Cheng, State of the art of intraocular lens manufacturing, Int J Adv Manuf Technol 98 (5–8) (2018) 1103–1130. [61] P. Narang, R. Steinert, B. Little, A. Agarwal, Intraocular lens scaffold to facilitate intraocular lens exchange, J Cataract Refract Surg 40 (9) (2014) 1403–1407. [62] J. Alio, A. Abdelghany, R. Fernández-Buenaga, Management of residual refractive error after cataract surgery, Current Opinion in Ophthalmology 25 (4) (2014) 291–297. [63] D. Apple, J. Sims, Harold Ridley and the invention of the intraocular lens, Survey of Ophthalmology 40 (4) (1996) 279–292. [64] J.D. Bartlett, S.D. Jaanus, Clinical Ocular Pharmacology, 4th ed., Butterworth Heinemann, 2001. [65] A. Dyrda, A. Martínez-Palmer, D. Martín-Moral, A. Rey, A. Morilla, M. Castilla-Martí, J. Aronés-Santivañez, Clinical Results of Diffractive, Refractive, Hybrid Multifocal, and Monofocal Intraocular Lenses, Journal of Ophthalmology (2018) 1–12. [66] R.M. Kershner, Keratolenticuloplasty: Arcuate keratotomy for cataract surgery and astigmatism, JCRS Volume 21 (3) (1995) 274–277. https://doi.org/10.1016/ S0886-3350(13)80131-9. [67] R.S. Snell, M.A. Lemp, Clinical Anatomy of the Eye, Second edition, Blackwell Publishing, Oxford, 1998. [68] I. Wormstone, L. Wang, C. Liu, Posterior capsule opacification, Experimental Eye Research 88 (2) (2009) 257–269.
Further reading [1] Y. Liu, M. Wilkins, T. Kim, B. Malyugin, J. Mehta, Cataracts, Lancet 390 (10094) (2017) 600–612. [2] I. Wormstone, L. Wang, C. Liu, Posterior capsule opacification, Exp Eye Res 88 (2) (2009) 257–269.