*3.1.4 Deepening the future*

In this stage, the most plausible futures that could occur up to the year 2100 are defined and projected through stratified causal analysis. **Table 2** shows the different hypotheses proposed and levels of causality in the futures analysed, providing a more concrete vision of each one of them, which allows the information processed in the previous stages to be articulated and refined.


**Sensors for Gait, Posture, and Health Monitoring**  Volume 2

Printed Edition of the Special Issue Published in *Sensors*  Thurmon Lockhart Edited by

www.mdpi.com/journal/sensors

## **Sensors for Gait, Posture, and Health Monitoring**


Introductory Chapter: Refractive Surgery

*Maja Bohač and Mateja Jagić*

#### **1. Introduction**

Refractive surgery today includes surgical procedures by which it is possible to reduce or eliminate a certain type of refractive error [1]. To date, with advances in technology, it has evolved far beyond the standard keratorefractive surgery. Thanks to the development of femtosecond technology and lasers, the precision of the LASIK procedure has been raised to a new level, and new keratorefractive methods, such as SMILE, have been developed [2]. To address refractive errors in patients who do not meet the criteria for standard laser surgery, phakic lens implantation stands as a safe surgical treatment with the possibility of correcting extreme refractive errors. We also witnessed the development of surgical methods for the correction of presbyopia with new laser ablation profiles, intracorneal implants, and the introduction of new generations of presbyopia-correcting intraocular lenses (IOLs). Extensive developments in methods of corneal biomechanics and topography analysis have led to easier identification of patients who are potentially risky candidates due to the possible development of keratectasia [3, 4]. Currently, most ophthalmic practice works on the principle of validating preoperative data by physicians, while in the future we are likely to face an era of artificial intelligence and the implementation of machine learning as a more precise way of finding appropriate parameters or functions to classify input data from large amounts of training data. This would greatly simplify the method of detecting borderline candidates for keratorefractive procedure, discriminating keratoconus from normal corneas, and finding the best-suitable IOL for providing complete spectacle independence without compromising functional vision and optical quality [3–5].

#### **2. Refractive surgery**

#### **2.1 Preoperative evaluation for refractive surgery**

For patients seeking spectacle independence, detailed preoperative assessment plays a key role in determining a safe and effective outcome. Examination for refractive surgery begins with taking a detailed medical history that includes systemic status, medication, allergies, ocular status, and history of contact lens use. The examination itself consists of a detailed biomicroscopic examination of the anterior and posterior segments of the eye, and the measurement of intraocular pressure. Refraction is the most important part of the preoperative examination. Each patient needs to determine the manifest refraction, monocular uncorrected, and

best-corrected visual acuity at distance and near. In addition to the examination, it is mandatory to record the pupil size in photopic, mesopic, and scotopic conditions, corneal topography and tomography with placido-based curvature topographic systems, pachymetry, biometry, wavefront aberrometry, evaluation of tear film, determination of ocular dominance, ocular motility, and specular microscopy [6–10]. In addition to standard corneal topography, evaluation of corneal biomechanics is a good clinical adjunct in process of detecting subclinical keratoconus among eyes clinically deemed to have seemingly normal topography. Next to standard topography, corneal biomechanics analysis, as at the Oculus CORVIS tonometer, is gradually being introduced into practice today [11, 12]. Newer models of high-resolution sweptsource OCT (SS-OCT) have been generating corneal epithelial thickness maps with standard anterior segment metrics, which is going to play a role in planning keratorefractive surgery and identification of early keratoconus [13]. Currently, modern wavefront aberrometers are incorporating corneal topography systems to calculate the contribution of corneal aberrations (anterior and posterior), and internal aberration (from the crystalline lens) to complete ocular wavefront. Therefore, taking into account the available data, clinicians are able to decide on the type of personalized (customized) ablation profiles [14, 15]. In cataract surgery or CLE/RLE candidates, besides standard preoperative assessment, IOL power calculation is crucial data for ensuring an effective surgery result. Calculation formulas are undergoing continuous improvements, with the latest formulas having shown promising precision and less refractive surprises [16]. As previously mentioned, machine learning technologies could create classification models using algorithms trained from data for achieving better results. One of the examples that are already present in clinical practice is the Kane formula [17].

It is also important to discuss the reasons for undergoing refractive surgery to identify patients with unrealistic expectations. It is extremely important to explain to patients that refractive procedures primarily serve to reduce spectacle independence in everyday situations.

#### **2.2 Keratorefractive surgery**

#### *2.2.1 History of keratorefractive surgery*

The beginnings of refractive surgery date back to ancient times. The first written records of cataract surgery date back to ancient Egypt in the fifth century BC [18]. The development of modern refractive surgery began in the mid-twentieth century. Tsutomu Sato introduced anterior and posterior keratotomy into clinical practice, and in 1939 published his results [19, 20]. The method is being further developed by Russian scientists Beliaev, Durnev, Yenaliev, and Fyodorov, who eventually introduced the radial keratotomy procedure to correct myopia [21–24]. Later on, José Barraquer in Colombia started developing the idea of lamellar corneal surgery to change the shape of the cornea. The idea arose from the observation that lamellar keratoplasty leads to a reduction in the cone in patients with keratoconus, and consequently to a reduction in myopia. In 1964, Barraquer described the principles of lamellar corneal surgery and called the procedure "keratomileusis," which means the formation of the cornea [25–27]. The development of excimer lasers began in the 1970s with experiments on a combination of rare gases (such as argon and xenon) and halogen gases (such as fluorine and chlorine) used as laser media. Trokel and Srinivasan were the

#### *Introductory Chapter: Refractive Surgery DOI: http://dx.doi.org/10.5772/intechopen.104578*

first to suggest that an excimer laser could have unique qualities for performing corneal surgery. In 1983, they suggested that such a laser could be used to remove tissue lamellae to change the curvature of the cornea and make precise incisions in the cornea [28, 29]. Theo Seiler was the first person to use an excimer laser on the human eye. In 1985 he performed astigmatic keratotomy, and in 1986 he performed the first phototherapeutic keratectomy (PTK) [30–32]. Munnerlyn et al. developed a computer-generated algorithm that links the diameter of the treatment zone to the depth of ablation to induce a specific diopter change in the cornea. An algorithm known as the Munnerlyn formula was used to develop laser patterns for inducing specific changes in corneal curvature to achieve the desired diopter change [33]. Laser *in situ* keratomileusis (LASIK) is a modification of Barraquer's keratomileusis and automated lamellar keratoplasty [34, 35]. The first method was developed by Lucio Buratto and involved the creation of a corneal lenticule (free flap) with a microkeratome, then excimer laser ablation of the posterior surface of the cornea, and re-suturing of the corneal lenticule [36]. In the meantime, Ioannis Pallikaris was developing a method in another way. The method involved creating a lamellar corneal flap with a microkeratome of his design and using an excimer laser to remodel the remaining corneal stroma under the flap. Palikaris coined the term of the method "Laser *in situ* keratomileusis" (LASIK) [37, 38]. The first clinical femtosecond laser approved by the FDA for refractive surgery use was the IntraLase FS, launched in 2003 [39–41]. In 2007, new low pulse energy and high pulse frequency Fs laser was introduced by Ziemer – FEMTO LDV. Since 2009, versions of Fs laser systems for use in cataract surgery, such as the first LensX, have also begun to develop in practice [42]. The first clinical version of a lenticule extraction procedure was introduced in the clinical treatment of refractive surgery patients in 2007 [42] as "FLEx" (Femtosecond Lenticule Extraction). A refined surgical version, small-incision lenticule extraction (SMILE) was introduced by Carl Zeiss Meditec and in a short period has replaced FLEx in clinical use [43]. Currently, novel laser systems for SMILE procedure are introduced by ATOS from SCHWIND eye-tech solutions (SmartSight procedure) and ZIEMER LDV Z8 from Ziemer Ophthalmic Systems AG (CLEAR procedure, Corneal Lenticule Extraction for Advanced Refractive correction).

#### *2.2.2 Photorefractive keratectomy (PRK)*

Photorefractive keratectomy (PRK) involves the use of an excimer laser on the anterior surface of the cornea to change the refractive status of the eye by changing the curvature of the cornea [44–46]. Except for refractive purposes, excimer laser surface ablation is used in the treatment of corneal scars and dystrophies when it is called phototherapeutic keratectomy (PTK) [47]. PRK is considered the method of choice, both refractive and therapeutic, in patients with basal membrane dystrophy, given that postoperatively better epithelial adherence occurs [48]. It is indicated in myopia from 1.0 to 6.0D, hyperopia up to 3.0D, and astigmatism up to 6.0D. Treatment of higher corrections is not recommended due to the risk of postoperative corneal opacity [49]. The surgical technique involves removal of the epithelium by excimer laser (transepithelial PRK), knife, 18–20% ethanol alcohol, or sponge. After epithelial removal, excimer laser ablation is performed. After excimer laser ablation, 0.02% mitomycin C is optionally applied to prevent corneal clouding. Postoperative recovery includes postoperative discomfort caused by epithelial erosion and gradual recovery of visual acuity during epithelial healing (within 72 h).

#### *2.2.3 Laser-assisted subepithelial keratectomy (LASEK/epi-LASIK)*

LASEK was firstly performed by Dimitri Azar in 1996 and he called it PRK with "Alcohol assisted flap PRK" [50, 51]. The method was named LASEK by Massimo Camellin in 1999, who popularized the technique [52, 53]. The technique involves applying 20% ethanol to the epithelium for 30 seconds to weaken the hemidesmosomal connections between the epithelium and the Bowman's membrane, leading to the formation of an epithelial sheet that is easily removed before excimer laser ablation and repositioned at the original position. Epi-LASIK was described by Palikaris et al. [54]. The technique involves the use of an automated knife, similar to a microkeratome, to remove epithelium without the use of alcohol. Disadvantages of the method are the possibility of treating only myopia, and the inability to predict the level of postoperative pain and prolonged epithelial healing.

#### *2.2.4 Laser in situ keratomileusis (LASIK)*

Laser *in situ* keratomileusis (LASIK) is the most commonly performed surgical technique for the correction of most refractive errors [55, 56]. LASIK is performed in two steps and combines lamellar surgery with excimer laser application. The first step involves the formation of the anterior corneal flap, its lifting to expose the stroma of the cornea. Today, two technologies are available for flap formation—mechanical microkeratomes and femtosecond lasers, known as femtosecond LASIK (FsLASIK). The second step consists of applying an excimer laser to the stroma of the cornea to change the curvature of the corneal anterior surface. Upon completion of the excimer laser action, the flap is repositioned to its original position [37, 57, 58]. The advantages of LASIK over superficial ablations are the ability to treat a wider range of refractive errors, faster vision recovery, less postoperative discomfort, and lower incidence of postoperative corneal or scar fogging in higher refractive errors. The main disadvantages of the method are the complications related to the creation of the flap, and the risk of iatrogenic keratectasia [59–61].

#### *2.2.5 Femtosecond refractive lenticule extraction (RELx) and small-incision lenticule extraction (SMILE)*

Femtosecond refractive lenticular extraction (RELx) is a corneal refractive procedure based on intrastromal refractive lenticular extraction. In the RLEx procedure, the lenticule was accessed by creating a front corneal flap similar to the LASIK flap, while in the SMILE procedure, the lenticule, located under a 120–130 μm thick cap is accessed through a small 2–4 mm incision on the anterior surface of the cornea. The shape and size of the lenticule are based on a mathematical calculation for the correction of a specific refractive error, and the location and amount of tissue extracted are similar to that of LASIK. The advantages of the method are related to the absence of possible complications related to the formation of the flap, less impact on the biomechanical stability of the cornea, less pronounced dryness of the eye, and less induced aberrations of higher order. The main disadvantages of the method are the possibility of treating only myopia and lower amounts of astigmatism. In case of residual refractive error, currently, only a surface ablation procedure is advised for correction [62–65].

#### *2.2.6 Multifocal laser ablation profiles*

Multifocal laser ablations for the treatment of presbyopia are still in the developmental stage. The multifocal cornea produces a simultaneous image on the retina, and the brain selects the appropriate image depending on whether the person is looking into the distance or at close range while the other image remains blurred. Potential side effects of these procedures are dysphotopsia and monocular diplopia. In this type of ablation protocol, the laser is used to create a multifocal surface on the cornea (changing the strength of the refractive gradient over the pupil) to correct ametropia at a distance and near. A central hyper-positive zone is created for proximity correction, leaving the middle corneal periphery for distance correction. Since some studies reported an unacceptable rate of losing CDVA using this kind of protocol, the procedure did not get widespread clinical use [66–68]. In recent times, the correction of presbyopia aims the change corneal asphericity and thus, using spherical aberration, increasing the depth of focus. The protocol is called Laser Blended Vision (LBV) and currently has been reported far better tolerated than multifocal ablation procedures [69].

#### **2.3 Corneal implants/inlays**

Spectacle independence is all the more sought after, so new surgical treatments are being invented to provide glasses-free life. The idea of keratophakia brought new light to presbyopia treatment [70, 71]. One of the introduced treatments initiated by this idea was corneal inlays [72–75]. Raindrop is a corneal inlay shaped like a clear lenticule made of hydrogel, which is permeable to oxygen, fluids, and nutrients. The lens is 2 mm wide, 32 μm thick in the center with decreasing thickens to about 10 μm in the periphery, and has no refractive power; therefore, it induces hyperpolate corneal shape allowing good near and intermediate vision with negligibly affected distance vision. It is placed in the non-dominant eye under the corneal flap or intracorneal pocket at 120–200 μm depth at the center of the light constricted pupil [72–74]. Until 2017 around 4000–6000 Raindrops were implanted worldwide but in November 2018 the manufacturer asked for a device recall due to postoperative haze [76, 77]. Kamra inlay uses the pinhole principle to facilitate near vision. This opaque ring shaped inlay is made of polyvinylidene fluoride and carbon. It is 6 µm thick, 3.6 mm diameter wide with a central 1.6 mm aperture. The inlay is placed in the nondominant eye 250 μm deep into the lamellar corneal pocket. If LASIK is done earlier, the inlay is placed 100–110 μm below the corneal flap and centration is based on the first Purkinje image. Around 20,000 Kamra inlays have been implanted and generally, there was a high satisfaction rate with both distant and near vision [75, 78, 79].

Presbia Flexivue Microlens is a refractive corneal inlay with a plano central zone surrounded by rings of varying additional power between +1.25D and + 3.5D. It is 3 mm wide, 15–20 μm thick, and is made of hydroxyethyl methacrylate and methyl methacrylate. It is placed over the first Purkinje image in a femtosecond creating a corneal pocket that is 280–300 μm deep. The overall satisfaction among patients was high but between other inlays, UCDVA showed a significant decrease from preoperative to postoperative values, but no changes in binocular UCDVA [74, 75, 80–82]. Best indications for corneal inlays are phakic, presbyopic patients, 41 to 65 years of age, who have low manifest refraction, who do not require correction for clear distance vision, but who do require near correction [78, 83]. Inlays are also indicated as a therapeutic model in keratoconus eyes. One of the most used ones is the Intacs

corneal implant by Additional Technology Inc. It consists of two segments designed to be placed in the periphery of the cornea, at approximately two-thirds depth, and are surgically inserted through a small radial incision in the corneal stroma [84, 85]. They are composed of two clear segments made from polymethylmethacrylate (PMMA), each having an arc length of 150°, and are available in six thicknesses—0.210, 0.250, 0.300, 0.350, 0.400 and 0.450 mm [86]. Aimed populations that can benefit from Intacs are patients with keratoconus older than 21 years of age who have progressive vision deterioration, clear corneas with at least 450 μm corneal tissue at the proposed incision site and transplantation as the only remaining treatment option. Contraindications for Intacs are corneas below 449 μm at the incision site, patients with autoimmune and immunodeficiency disorders, pregnant and nursing women, patients with recurrent corneal erosion and other corneal dystrophies, and patients taking isotretinoin or amiodarone hydrochloride [86, 87].

#### **2.4 Phakic intraocular lenses (pIOLs)**

Phakic intraocular lenses (pIOLs) are one of the available surgical option for the treatment of ametropia [88]. When the natural crystalline lens is clear and usually has retained its accommodative function pIOLs are used. They are an effective and relatively safe option for surgical treatment of refractive errors with a special emphasis on very high refractive errors in both myopic and hyperopic eyes [89]. It has been generally accepted that refractive surgery is an effective and safe way of treating refractive errors. The first choice for surgical treatment is the cornea, the ubiquitous and commoditized nature of excimer lasers today has popularized surgical options [90]. The issue is when a refractive surgeon is met with a challenge of very high prescriptions or other confounding factors, such as thin corneas, or other factors that increase the risk for an adverse outcome for corneal refractive surgery. The most commonly accepted range for laser vision correction in corneal refractive surgery is between 10 diopters of myopia to 5 diopters of hyperopia with up to 5 diopters of cylindrical correction. For patients with high motivation and a clear crystalline lens with no presbyopia, that fall outside these limits or have other factors connected to a potentially adverse outcome, phakic IOLs present a great option [89]. There are two refractive pIOLs approved for correcting refractive errors—anterior chamber and posterior chamber pIOLs [91].

#### *2.4.1 Anterior chamber pIOLs*

Anterior chamber pIOLs in use today are made by Ophtec, a Dutch company, their anterior chamber lens is called ArtiLens, there are two types—a flexible version ArtiFlex and a rigid PMMA version Artisan [92]. These lenses were at one time distributed by AMO, now Johnson & Johnson Vision, and many surgeons will use them under their old names Veriflex and Verisyse. The ArtiFlex is a foldable pIOL that is inserted through an opening of 3.2 mm, it is fixated on the iris using an enclavation technique, the powers range from −14.5 to −2.0, there is a toric version available with powers from −13.5 to −1.0 and cylinder ranging from −5.0 to −1.0. The Artisan is a rigid PMMA pIOL that has an optic diameter of 5 or 6 mm the powers available range from −15.5 to +12.0. These pIOLs are also fixated on the iris but as they are not foldable they require a larger incision either 5 or 6 mm depending on the optic diameter [92]. There was another option, Alcon CACHET, an angle-supported anterior chamber pIOL was an additional variant, but was discontinued during 2014 due to endothelial cell loss as a serious side effect. Endothelial cell loss occurs due to contact

of endothelium layer and pIOL surface, causing corneal endothelial decompensation which leads to corneal edema (overhydration), and in the advanced stage, bullous keratopathy [93].

#### *2.4.2 Posterior chamber pIOLs*

Posterior chamber phakic IOLs are a different approach that wants to avoid endothelial cell loss by moving the pIOL behind the iris plane. But by moving the pIOL behind the iris and just above the crystalline lens, there are new potential issues that can arise. The first issue is angle closure glaucoma, as the pIOL can reduce the aqueous fluid outflow by pushing the iris angle, inducing very high IOP. Previous generations of pIOL designs required a small iridotomy creation to facilitate aqueous fluid outflow [94]. The second issue is that the pIOL could block the flow of fluid around the optic and into the anterior chamber, the iridotomy was also beneficial in these cases. The third issue was in case of pIOL touching the capsule of the crystalline lens, an early onset cataract can form [95]. The three big issues today are mostly avoided by the use of modern diagnostic tools and surgical experience. The new posterior chamber pIOLs have very strict sizing guides to adjust the size of the pIOL to the sulcus of the patient to avoid the lens closing the iridocorneal angle, proper sizing also ensures a large enough vault between the pIOL and crystalline lens, and the block of fluid flow is rectified by new pIOLs with a center hole for unobstructed flow [96]. Currently, there is only one generally adopted posterior chamber pIOL, STAAR Surgical Visian ICL. STAAR Surgical has patented the design and material of their lenses, these are very soft collamer-based pIOLs that are implanted with minimally invasive 3.2 mm injectors, and the folded lens is placed in the sulcus after it unfolds in the iris plane. Visian ICL comes in spherical powers from −18.0 to +10.0 diopters, and there is a toric variant from +0.5 to +6.0 diopters of the cylinder. The ICL is produced in four sizes, 12.1 mm, 12.6 mm, 13.2 mm, and 13.7 mm to fit the size of the sulcus of the patient as best as possible [92, 97]. STAAR Surgical Visian ICL is a great option for patients that are not suitable candidates for corneal refractive surgery and are not ready for refractive lens exchange due to their age.

#### **2.5 Cataract surgery and refractive lens exchange**

#### *2.5.1 History of cataract surgery and evolution of intraocular lenses*

The first records of cataract surgery date back to antiquity, where couching was the only method of resolving optical path opacity, but without replacing the refractive property (power) of the removed crystalline lens [18, 98]. At a later age, about 600 BC a primitive version of extracapsular cataract extraction was described by an Indian surgeon Sushruta [99]. It was not until the 18th century, in 1947, that the forerunner of modern cataract surgery—extracapsular cataract extraction (ECCE) was performed by Jacques Daviel [100, 101]. A few years later, in 1753 Samuel Sharp performed intracapsular cataract extraction (ICCE) [102]. During the next decade, ICCE was considered as a method of choice for cataract surgery. The main difficulties of these procedures were related to complications, such as high risks of postoperative infection, prolonged wound healing (10–12 mm), vitreous prolapse, and retinal ablation. In 1961 Tadeusz Krwawicz invented cryoextraction, a freezing method for removing the cataractous lens [103]. The introduction of phacoemulsification in 1967 by Dr. Charles Kelman was the basis and beginning of today's modern cataract surgery [104]. Concurrently,

the idea of replacing the cataractous lens with artificial optics was developing, starting from Sir Harold Ridley who observed in the 2nd World War that one of the pilots had a plastic shrapnel eye injury, without causing foreign body reaction. Guided by that, he developed the first intraocular lens (IOL) made of polymethylmethacrylate (PMMA) for insertion in the eye after cataractous lens removal [105]. Various materials have been tried for IOLs, and finally in the late 1970s flexible, silicone lens was brought into use. The primary aim of introducing flexible IOLs was to avoid the disadvantages of PMMA, such as larger incisions and consequent postoperative astigmatism. Silicone IOLs rapidly adopted and conquered the market during the 1980s [106]. In 1989, the first commercially available three-piece silicone IOL was introduced (PhacoFlex SI-18 by AMO, now Johnson & Johnson Vision) [107]. Further on, in the 1980s, Barret developed the first hydrogel IOL made of soft hydrophilic material (IOGEL PC-12) implanted in 1983 [108]. Following closely, hydrophobic acrylic IOLs were developed, which represent the most common implanted foldable IOL today [109, 110]. The combination of innovations, such as the phacoemulsification technique, foldable IOL, and even the use of topical anesthesia [111], has ensured the development of modern cataract surgery. Over the next few decades, attempts were made to introduce lasers into ophthalmic surgery. Bille and Schanzlin were the first to propose ultrashort laser pulses for treating cataracts back in 1993 [112] and the first clinical results of femtosecond laser use in cataract surgery (Femtosecond-Laser-Assisted cataract surgery - FLACS) was reported by Nagy et al. [113]. In parallel with the development of surgical methods, the evolution of an IOL design has moved in the direction of correcting all working distances, trying to minimize or even remove spectacle independence [114]. With the introduction of multifocal lenses, an era began in which cataract surgery became refractive surgery. Since the 1980s, bifocal, trifocal, quadrifocal IOLs have been designed, and toric IOLs have been introduced to correct astigmatism [115]. As refractive surgery has developed widely, with increasing needs of working patients, occasional refractive surprises became a problem in clinical practice due to patient dissatisfaction. In this name, supplementary IOLs, such as SulcoFlex by Rayner, have been developed as one of the possible surgical correction options [116–119]. Accommodative IOL was developed to provide better distance corrected near visual acuity and higher levels of spectacle independence than standard monofocal IOLs but also producing minimal unwanted visual disturbances, such as halos and glares and contrast sensitivity compared with multifocal IOLs. The first accommodative FDA-approved IOL was CrystaLens by Bausch & Lomb Inc. [120, 121]. In an attempt of overcoming the drawbacks of multifocal and accommodative IOLs, EDOF design was developed, with the first FDA approval for Tecnis Symfony by Johnson & Johnson Vision [122]. The main principle of EDOF design is a single elongated focal point that enhances the depth of focus (range of vision), and therefore significantly reduces potential halos and glares induced by multifocal IOL by eliminating the overlapping of near and far images [123–125].

#### *2.5.2 Monofocal intraocular lenses*

Monofocal intraocular lenses are the most common type of IOL used in cataract surgery. They are designed to correct a patient's visual acuity for far distances, with the need for an optical aid for near vision. Lenses are usually indicated in patients with extremely high myopic or hyperopic refraction, amblyopia, macular degeneration, dry eye syndrome, history of previous ocular surgery, ocular trauma, autoimmune diseases, or connective tissue diseases.

#### *Introductory Chapter: Refractive Surgery DOI: http://dx.doi.org/10.5772/intechopen.104578*

Currently, monofocal IOLs are mainly represented as hydrophobic acrylic lenses with an aspheric surface design. Aspheric types of IOLs are eliminating positive spherical aberration of the prolate cornea, improving functional vision and reducing side effects, such as low contrast sensitivity or low night-driving performance. The functional benefit and optical advantages of aspheric IOL technology are related to pupil size, depth of focus, IOL centration, and customization. Since it is pupil-size dependent, some studies have shown that aspheric IOLs offer little or almost no benefit in smaller pupils [126–129]. Therefore, when it comes to customization, preoperative assessment is extremely important, which in addition to standard measurements includes corneal topographic analysis, and the values of corneal aberrations, especially spherical aberration. According to the obtained parameters, the final decision on the type of IOL is given.

#### *2.5.3 Presbyopia-correcting intraocular lenses*

With the development and increase in cataract surgical treatment, the patient's expectation regarding postoperative outcomes is also increasing, as they seek to achieve independence from spectacles and favorable visual outcomes at both near and far distances to meet the needs of everyday activities [130–132]. Nowadays, in a presbyopia-correcting pool of IOLs, multifocal and extended range of vision (EDOF) IOLs are most prevalent in clinical use. Multifocal IOLs in the initial variant had a diffractive design, and afterward, refractive design was introduced. Diffractive IOLs had one variant with or without apodization, where the central (near) area is surrounded by concentric rings with decreasing heights [133] and the second variant with an aspheric anterior surface and a posterior surface with diffractive rings [134, 135]. Refractive IOL design has an asymmetrical shape of the central (near) segment to provide a sort of transition between zones of IOL [136, 137]. Trifocal diffractive IOL was introduced to improve intermediate vision with a third focus, at 80 cm. The first one in clinical use was FineVision IOL by Physiol, further followed by At LISA tri by Zeiss, and RayOne Trifocal by Rayner. In comparison with a traditional trifocal IOL, quadrifocal IOL has three added powers for near and intermediate vision, providing more continuous vision. One example of IOL with quadrifocal design is PanOptix by Alcon, which uses a specific optical technology to redirect the focal point at 120 cm to the distance focal point for amplified performance [138].

After introducing a technology designed to improve the range of vision, especially at intermediate distances, EDOF IOLs gained high popularity in refractive cataract surgery. An EDOF technology development arose from the necessity to obviate drawbacks of monofocal and multifocal IOLs – providing better vision for intermediate distance without compromising functional vision, reducing contrast sensitivity, or inducing disturbances, such as halos and glares. Currently, there are four different EDOF technologies [139]—diffractive optics IOL (Tecnis Symfony and Synergy IOL, Tecnis Eyhance IOL by Johnson & Johnson Vision, and AT LARA by Zeiss- hybrid multifocals) [125, 140] non-diffractive optics IOL (AcrySof IQ Vivity IOL by Alcon and SiFI Mini WELL IOL by SIFI MedTech Srl.) [141, 142], small-aperture IOL (IC-8 IOL by AcuFocus Inc.) [143], and bioanalogic IOL (Wichterle IOL-Continuous Focus - WIOL-CF by Medicem) [144].

#### **Conflict of interest**

The authors declare no conflict of interest.

### **Acronyms and abbreviations**

### **Author details**

Maja Bohač\* and Mateja Jagić University Eye Hospital Svjetlost, Zagreb, Croatia

\*Address all correspondence to<EMAIL_ADDRESS>
© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Kim TI, Alio Del Barrio JL, Wilkins M, Cochener B, Ang M. Refractive surgery. Lancet. 2019;**393**:2085-2098

[2] Ang M, Mehta JS, Chan C, Htoon HM, Koh JC, Tan DT. Refractive lenticule extraction: Transition and comparison of 3 surgical techniques. Journal of Cataract and Refractive Surgery. 2014;**40**:1415-1424

[3] Arbelaez MC, Versaci F, Vestri G, Barboni P, Savini G. Use of a support vector machine for keratoconus and subclinical keratoconus detection by topographic and tomographic data. Ophthalmology. 2012;**119**:2231-2238

[4] Smadja D, Touboul D, Cohen A, Doveh E, Santhiago MR, Mello GR, et al. Detection of subclinical keratoconus using an automated decision tree classification. American Journal of Ophthalmology. 2013;**156**(237-46):e231

[5] Yousefi S, Yousefi E, Takahashi H, Hayashi T, Tampo H, Inoda S, et al. Keratoconus severity identification using unsupervised machine learning. PLoS One. 2018;**13**:e0205998

[6] Myung D, Schallhorn S, Manche EE. Pupil size and LASIK: A review. Journal of Refractive Surgery. 2013;**29**(11):734-741

[7] Rosen ES, Gore CL, Taylor D, Chitkara D, Howes F, Kowalewski E. Use of digital infrared pupilometer to assess patient suitability for refractive surgery. Journal of Cataract and Refractive Surgery. 2002;**28**(8):1433-1438

[8] Ambrosio R Jr, Alonso RS, Luz A, Cova Velarde LG. Corneal-thickness spatial profile and corneal-volume distribution: Tomographic indices to detect keratoconus. Journal of

Cataract and Refractive Surgery. 2006;**32**(11):1851-1859

[9] Albietz JM, McLennan SG, Lenton LM. Ocular surface management of photorefractive keratectomy and laser in situ keratomileusis. Journal of Refractive Surgery. 2003;**19**(6):636-644

[10] Snir M, Kremer I, Weinberger D, Sherf I, Axer-Siegel R. Decompensation of exodeviation after corneal refractive surgery for moderate to high myopia. Ophthalmic Surgery, Lasers & Imaging. 2003;**34**(5):363-370

[11] Roberts CJ, Mahmoud AM, Bons JP, Hossain A, Elsheikh A, Vinciguerra R, et al. Introduction of two novel stiffness parameters and interpretation of air puff-induced biomechanical deformation parameters with a dynamic Scheimpflug analyzer. Journal of Refractive Surgery. 2017;**33**:266-273

[12] Ambrosio R Jr, Lopes BT, Faria-Correia F, Salomao MQ, Buhren J, Roberts CJ, et al. Integration of Scheimpflug-based corneal tomography and biomechanical assessments for enhancing ectasia detection. Journal of Refractive Surgery. 2017;**33**:434-443

[13] Ang M, Baskaran M, Werkmeister RM, Chua J, Schmidl D, Aranha Dos Santos V, et al. Anterior segment optical coherence tomography. Progress in Retinal and Eye Research. 2018;**66**:132-156

[14] Amigo A, Martinez-Sorribes P, Recuerda M. Refractive changes induced by spherical aberration in laser correction procedures: An adaptive optics study. Journal of Refractive Surgery. 2017;**33**:470-474

[15] Gatinel D, Malet J, Dumas L. Polynomial decomposition method for ocular wavefront analysis. Journal of the Optical Society of America. A, Optics, Image Science, and Vision. 2018;**35**:2035-2045

[16] Shajari M, Kolb CM, Petermann K, Bohm M, Herzog M, de'Lorenzo N, et al. Comparison of 9 modern intraocular lens power calculation formulas for a quadrifocal intraocular lens. Journal of Cataract and Refractive Surgery 2018;44:942-948

[17] Connell BJ, Kane JX. Comparison of the Kane formula with existing formulas for intraocular lens power selection. BMJ Open Ophthalmology. 2019;**4**:e000251

[18] Ascaso F, Lizana J, Cristobal J. Cataract surgery in ancient Egypt. Journal of Cataract & Refractive Surgery. 2009;**35**(3):607-608. DOI: 10.1016/j. jcrs.2008.11.052

[19] Sato T. Treatment of conical cornea (incision of Descemet's membrane). Acta Soc Ophthalmol Jpn. 1939;**43**:544-555

[20] Sato T, Akiyama K, Shibata H. A new surgical approach to myopia. American Journal of Ophthalmology. 1953;**36**(61):823-829

[21] Yenaleyev FS. Experience in surgical treatment of myopia. Annals of Ophthalmology USSR. 1979;**3**:52-55

[22] Durnev VV. Characteristics of surgical correction of myopia after 16 and 32 peripheral anterior nonperforating incisions. In: Fyodorov SN, editor. Surgery for Anomalies in Ocular Refraction. Moscow: The Moscow Research Institute for Ocular Microsurgery; 1981. pp. 33-35

[23] Durnev VV, Ivanshina AA. Possibility of maximal elongation of incisions in radial keratotomy. In: Fyodorov SN, editor. Surgery for Anomalies in Ocular Refraction. Moscow: The Moscow

Research Institute for Ocular Microsurgery; 1981. pp. 19-22

[24] Fyodorov SN, Agranovsky AA. Longterm results of anterior radial keratotomy. Journal of Ocular Pharmacology and Therapeutics. 1982;**1**:217-223

[25] Barraquer JI. Keratomileusis. International Surgery. 1967;**48**(2):103-117

[26] Barraquer JI. Keratomileusis for myopia and aphakia. Ophthalmology. 1981;**88**(8):701-708

[27] Barraquer JI. The history and evolution of keratomileusis. International Ophthalmology Clinics. 1996;**36**(4):1-7

[28] Srinivasan R. Kinetics of the ablative photodecomposition of organic polimers in the far ultraviolet (193 nm). Journal of Vacuum Science and Technology B. 1983;**1**(4):923-926

[29] Trokel SL, Srinivasan R, Braren B. Excimer laser surgery of the cornea. American Journal of Ophthalmology. 1983;**96**(6):710-715

[30] Seiler T, Wolensak J. In vivo experiments with the excimer laser technical parameters and healing process. Ophthalmologica. 1986;**192**(2):65-70

[31] Seiler T, Kahle G, Kriegerovski M. Excimer laser (193nm) myopic keratomileusis in sighted and blind human eyes. Refractive & Corneal Surgery. 1990;**6**(3):165-173

[32] Seiler T. Photorefractive keratectomy: European experience. In: Thompson FB, PJ MD, editors. Color Atlas/Text of Excimer Laser Surgery: The Cornea. New York: Igaku-Shoin; 1993. pp. 53-62

[33] Munnerlyn CR, Koons SJ, Marshall J. Photorefractive keratectomy: A technique for laser refractive surgery.

*Introductory Chapter: Refractive Surgery DOI: http://dx.doi.org/10.5772/intechopen.104578*

Journal of Cataract and Refractive Surgery. 1988;**14**(1):46-52

[34] Ruiz L, Rowsey J. In situ keratomileusis. Investigative Ophthalmology & Visual Science. 1988;**29**:392

[35] Peyman GA. Method for modifying corneal curvature. US patent 4840175. 1989

[36] Buratto L, Ferrari M, Rama P. Excimer laser intrastromal keratomileusis. American Journal of Ophthalmology. 1992;**113**(3):291-295

[37] Pallikaris I, Papatsanaki M, Stathi E, Frenschock O, Georgiadis A. Laser in situ keratomileusis. Lasers in Surgery and Medicine. 1990;**10**(5):463-468

[38] Pallikaris I, Papatzanaki M, Siganos D, Tsilimbaris MK. A corneal flap technique for laser in situ keratomileusis. Human studies. Archives of Ophthalmology. 1991;**109**(12):1699-1702

[39] Ratkay-Traub I, Juhasz T, Horvath C, Suarez C, Kiss K, Ferincz I, et al. Ultrashort pulse (femtosecond) laser surgery: Initial use in LASIK flap creation. Ophthalmology Clinics of North America. 2001;**14**:347-355

[40] Kezirian GM, Stonecipher KG. Comparison of the IntraLase femtosecond laser and mechanical keratomes for laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2004;**30**:804-811

[41] Lubatschowski H, Maatz G, Heisterkamp A, Hetzel U, Drommer W, Welling H, et al. Application of ultrashort laser pulses for intrastromal refractive surgery. Graefe's Archive for Clinical and Experimental Ophthalmology. 2000;**238**:33-39

[42] Nagy ZZ, McAlinden C. Femtosecond laser cataract surgery. Eye and Vision. 2015;**2**:1-8

[43] Wei S, Wang Y. Comparison of corneal sensitivity between FS-LASIK and femtosecond lenticule extraction (ReLEx flex) or small-incision lenticule extraction (ReLEx smile) for myopic eyes. Graefe's Archive for Clinical and Experimental Ophthalmology. 2013;**251**:1645-1654

[44] Puliafito CA, Steinert RF, Deutsch TF, Hillenkamp F, Dehm EJ, Adler CM. Excimer laser ablation of the cornea and lens: Experimental studies. Ophthalmology. 1985;**92**(6):741-748

[45] Gartry DS, Kerr Muir MG, Marshal J. Excimer laser photorefractive keratectomy: 18 month follow up. Ophthalmology. 1992;**99**(8):1209-1219

[46] Campos M, Nielsen S, Szerenyi K, Garbus JJ, McDonnell PJ. Clinical follow-up of phototherapeutic keratectomy for treatment of corneal opacities. American Journal of Ophthalmology. 1993;**115**(4):433-440

[47] Sher NA, Bowers RA, Zabel RW, i sur. Clinical use of 193nm excimer laser int he treatment of corneal scars. Archives of Ophthalmology. 1991;**109**(4):491-498

[48] Örndahl MJ, Fagerholm PP. Phototerapeutic keratectomy for mapdot-fingerprint corneal dystrophy. Cornea. 1998;**17**(6):595-599

[49] Lee YG, Chen WY, Petrol WM, Cavanagh HD, Jester JV. Corneal haze after photorefractive keratectomy using different epithelial removal techniques: Mechanical debridement versus laser scrape. Ophthalmology. 2001;**108**(1):112-120

[50] Azar DT, Taneri S. LASEK. In: Azar DT, editor. Refractive Surgery. 2nd ed. Philadelphia: Elsevier Inc; 2007. pp. 239-247

[51] Azar DT, Ang RT, Lee JB. Laser subepithelial keratomileusis: electron microscopy and visual outcomes of flap photorefractive keratectomy. Current Opinion in Ophthalmology. 2001;**12**(4):323-328

[52] Camellin M. Laser epithelial keratomileusis for myopia. Journal of Refractive Surgery. 2003;**19**(6):666-670

[53] Cimberle M, Camellin M. LASEK may offer the advantages of both LASIK and PRK. Ocular Surgery News. International Edition. 1999;**10**:28

[54] Pallikaris IG, Naoumidi II, Kalyvianaki MI, Katsanevaki VJ. Epi LASIK: Comparative histological evaluation of mechanical and alcoholassisted epithelial separation. Journal of Cataract and Refractive Surgery. 2003;**29**(8):1496-1501

[55] Duffey RJ, Learning D. US trends in refractive surgery. 2003 ISRS/AAO survey. Journal of Refractive Surgery. 2005;**21**(1):87-91

[56] Schmack I, Auffarth GU, Epstein D, Holzer MP. Refractive surgery trends and practice style in Germany over a 3 year period. Journal of Refractive Surgery. 2010;**26**(3):202-208

[57] Gatinel D. LASIK for myopia, hyperopia and astigmatism. In: Azar DT, editor. Refractive Surgery. 2nd ed. Philadelphia: Elsevier Inc; 2007. pp. 165-182

[58] Carr JD, Stulting RD, Thompson KP, Waring GO 3rd. Laser in situ keratomileusis: surgical technique. Ophthalmology Clinics of North America. 2001;**14**(2):285-294

[59] Moshirfar M, Gardiner JP, Schliesser JA, i sur. Laser in situ keratomileusis flap complications using mechanical microkeratome

versus femtosecond laser: Retrospective comparison. Journal of Cataract and Refractive Surgery. 2010;**36**(11):1925-1933

[60] Twa MD, Nichols JJ, Joslin CE. Characteristics of corneal ectasia after LASIK for myopia. Cornea. 2004;**23**(5):447-457

[61] Ou RJ, Shaw EL, Glasgow BJ. Keratectasia after laser in situ keratomileusis (LASIK): Evaluation of the calculated residual stromal bed thickness. American Journal of Ophthalmology. 2002;**134**(5):771-773

[62] Reinstein DZ, Carp GI, Archer TJ, Gobbe M. Outcomes of small incision Lenticule extraction (SMILE) in low myopia. Journal of Refractive Surgery. 2014;**30**(12):812-818

[63] Blum M, Kunert K, Schroder M, Sekundo W. Femtosecond lenticule extraction for the correction of myopia: Preliminary 6-month results. Graefe's Archive for Clinical and Experimental Ophthalmology. 2010;**248**(7): 1019-1027

[64] Shah R, Shah S, Sengupta S. Results of small incision lenticule extraction: All-in-one femtosecond laser refractive surgery. Journal of Cataract and Refractive Surgery. 2011;**37**(1):127-137

[65] Pedersen IB, Bak-Nielsen S, Vestergaard AH, Ivarsen A, Hjortdal J. Corneal biomechanical properties after LASIK, ReLEx flex, and ReLEx SMILE by Scheimpflug-based dynamic tonometry. Graefe's Archive for Clinical and Experimental Ophthalmology. 2014;**252**(8):1329-1335

[66] Jung WS, Kim MJ, Park SH, Joo C. Multifocal corneal ablation for hyperopic presbyopes. Journal of Refractive Surgery. 2008;**24**(9):903-910

*Introductory Chapter: Refractive Surgery DOI: http://dx.doi.org/10.5772/intechopen.104578*

[67] Alarcón A, Anera RG, Soler M, Del Barco LJ. Visual evaluation of different multifocal corneal models for the correction of presbyopia by laser ablation. Journal of Refractive Surgery. 2011;**27**(11):833-836

[68] El Danasoury AM, Gamaly TO, Hantera M. Multizone LASIK with peripheral near zone for correction of presbyopia in myopic and hyperopic eyes: 1-year results. Journal of Refractive Surgery. 2009;**25**(3):296-230

[69] Reinstein DZ, Archer TJ, Gobbe M. Laser blended vision for presbyopia correction. In: Pallikaris IG, Plainis S, Charman WN, editors. Presbyopia: Origins, Effects and Treatment. Thorofare, NJ: SLACK Incorporated; 2012

[70] Barraquer JI. Modification of refraction by means of intracorneal inclusions. International Ophthalmology Clinics. 1966;**6**:53-78

[71] Barraquer JI. Keratophakia. Transactions of the ophthalmological societies of the United Kingdom. 1972;**92**:499-516

[72] Lindstrom RL, Macrae SM, Pepose JS, Hoopes PC Sr. Corneal inlays for presbyopia correction. Current Opinion in Ophthalmology. 2013;**24**:281-287

[73] Konstantopoulos A, Mehta JS. Surgical compensation of presbyopia with corneal inlays. Expert Review of Medical Devices. 2015;**12**:341-352

[74] Arlt E, Krall E, Moussa S, Grabner G, Dexl A. Implantable inlay devices for presbyopia: The evidence to date. Clinical Ophthalmology. 2015;**9**:129-137

[75] Moarefi MA, Bafna S, Wiley W. A review of presbyopia treatment with

corneal inlays. Ophthalmology and Therapy. 2017;**6**(1):55-65. DOI: 10.1007/ s40123-017-0085-7

[76] Yoo A, Kim JY, Kim MJ, Tchah H. Hydrogel inlay for presbyopia: Objective and subjective visual outcomes. Journal of Refractive Surgery. 2015;**31**:454-460

[77] FDA Class 1 recall of Raindrop Near Vision Inlay, (initiated Nov 2018; Create Mar 2019, Available from: https://www. accessdata.fda.gov/scripts/cdrh/cfdocs/ cfRes/res.cfm?ID=169984

[78] Acu Focus Inc. KAMRA Inlay, Informational Manual for Professional Use. CA, USA: U.S. Food and Drug Administration; 2015. Available from: https://www.accessdata.fda.gov/cdrh\_ docs/pdf12/p120023d.pdf

[79] Vukich JA, Durrie DS, Pepose JS, Thompson V, van de Pol C, Lin L. Evaluation of the small-aperture intracorneal inlay: Three year results from the cohort of the U.S. Food and Drug Administration clinical trial. Journal of Cataract and Refractive Surgery. 2018;**44**:541-556

[80] Malandrini A, Martone G, Menabuoni L, Catanese AM, Tosi GM, Balestrazzi A, et al. Bifocal refractive corneal inlay implantation to improve near vision in emmetropic presbyopic patients. Journal of Cataract and Refractive Surgery. 2015;**41**:1962-1972

[81] Limnopoulou AN, Bouzoukis DI, Kymionis GD, Panagopoulou SI, Plainis S, Pallikaris AI, et al. Visual outcomes and safety of a refractive corneal inlay for presbyopia using femtosecond laser. Journal of Refractive Surgery. 2013;**29**:12-18

[82] Baily C, Kohnen T, O'Keefe M. Preloaded refractive-addition corneal inlay to compensate for presbyopia

implanted using a femtosecond laser: One-year visual outcomes and safety. Journal of Cataract and Refractive Surgery. 2014;**40**:1341-1348

[83] ReVision Optics Inc. Raindrop near Vision Inlay, Information Manual for Professional Silver Spring, Maryland, USA: U.S. Food and Drug Administration; 2016. Available from: https://www.accessdata.fda.gov/cdrh\_ docs/pdf15/p150034c.pdf

[84] Vega-Estrada A, Alio JL. The use of intracorneal ring segments in keratoconus. Eye and Vision. 2016;**3**:8

[85] Vega-Estrada A, Alio JL, Brenner LF, Javaloy J, Plaza Puche AB, Barraquer RI, et al. Outcome analysis of intracorneal ring segments for the treatment of keratoconus based on visual, refractive, and aberrometric impairment. American Journal of Ophthalmology. 2013;**155**: 575-84.e571

[86] Additional Technology Inc. (2004) Intrastromal Corneal Ring Segment, INTACS: Information Manual for Professional Use. Silver Spring, Maryland, USA: U.S. Food and Drug Administration; Available from: https:// www.accessdata.fda.gov/cdrh\_docs/ pdf4/h040002c.pdf

[87] Warrak EL, Serhan HA, Ayash JG, et al. Long-term follow up of intracorneal ring segment implantation in 932 keratoconus eyes. Journal Français d'Ophtalmologie. 2020;**43**(10):1020-1024

[88] Kohnen T, Shajari M. Phake Intraokularlinsen [Phakic intraocular lenses]. Der Ophthalmologe. 2016;**113**(6):529-538. German. DOI: 10.1007/s00347-016-0283-z

[89] Nanavaty MA, Daya SM. Refractive lens exchange versus phakic intraocular lenses. Current Opinion in Ophthalmology. 2012;**23**:54-61

[90] Sugar A, Rapuano CJ, Culbertson WW, Huang D, Varley GA, Agapitos PJ, et al. Laser in situ keratomileusis for myopia and astigmatism: Safety and efficacy: A report by the American Academy of ophthalmology. Ophthalmology. 2002;**109**:175-187

[91] Ang M, Gatinel D, Reinstein DZ, Mertens E, Alió Del Barrio JL, Alió JL. Refractive surgery beyond 2020. Eye (London, England). 2021;**35**(2):362-382. DOI: 10.1038/s41433-020-1096-5

[92] Hou C, Li H, Li J, Li J, Peng H, Wang Q. Artisan versus Artiflex phakic intraocular lens implantation in the treatment of moderate to high myopia: meta-analysis. BMC Ophthalmology. 2021;**21**(1):171. DOI: 10.1186/ s12886-021-01930-6

[93] Galvis V, Villamil JF, Acuña MF, Camacho PA, Merayo-Lloves J, Tello A, et al. Long-term endothelial cell loss with the iris-claw intraocular phakic lenses (artisan®). Graefe's Archive for Clinical and Experimental Ophthalmology. 2019;**257**(12):2775-2787. DOI: 10.1007/ s00417-019-04506-9

[94] Pop M, Payette Y. Refractive lens exchange versus iris-claw artisan phakic intraocular lens for hyperopia. Journal of Refractive Surgery. 2004;**20**:20-24

[95] Gonvers M, Bornet C, Othenin-Girard P. Implantable contact lens for moderate to high myopia: Relationship of vaulting to cataract formation. Journal of Cataract and Refractive Surgery. 2003;**29**:918-924

[96] Barsam A, Allan BD. Excimer laser refractive surgery versus phakic intraocular lenses for the correction of moderate to high myopia. Cochrane Database of Systematic Reviews. 2014;**6**:CD007679. DOI: 10.1002/14651858. CD007679.pub4

*Introductory Chapter: Refractive Surgery DOI: http://dx.doi.org/10.5772/intechopen.104578*

[97] Shen Y, Wang L, Jian W, Shang J, Wang X, Ju L, et al. Big-data and artificial-intelligence-assisted vault prediction and EVO-ICL size selection for myopia correction. The British Journal of Ophthalmology. 2021:bjophthalmol-2021-319618. DOI: 10.1136/bjophthalmol-2021-319618 [Online ahead of print]

[98] Feigenbaum A. Early history of cataract and the ancient operation for cataract. American Journal of Ophthalmology. 1960;**49**:305-326

[99] Grzybowski A, Ascaso FJ. Sushruta in 600 B.C. introduced extraocular expulsion of lens material. Acta Ophthalmologica. 2014;**92**(2):194-197. DOI: 10.1111/aos.1203

[100] Rucker CW. Cataract: A historical perspective. Investigative Ophthalmology. 1965;**4**:377-383

[101] Davis G. The evolution of cataract surgery. Missouri Medicine. 2016;**113**(1):58-62

[102] Hubbell AA. Samuel sharp, the first surgeon to make the corneal incision in cataract extraction with a single knife: A biographical and historical sketch. Medical Library and Historical Journal. 1904;**2**(4):1-268

[103] Nagy ZZ. History of cataract surgery from ancient times to today. Developments in Health Sciences. 2020;**2**(4):88-92. DOI: 10.1556/2066.2019. 00002 [Accessed: March 12, 2022]

[104] Kelman CD. Phaco-emulsification and aspiration. A new technique of cataract removal. A preliminary report. American Journal of Ophthalmology. 1967;**64**(1):23-35

[105] Apple DJ, Sims J. Harold Ridley and the invention of the intraocular

lens. Survey of Ophthalmology. 1996;**40**(4):279-292. DOI: 10.1016/ s0039-6257(96)82003-0

[106] Obstbaum SA. Development of foldable IOL materials. Journal of Cataract and Refractive Surgery. 1995;**21**(3):233. DOI: 10.1016/ s0886-3350(13)80119-8

[107] Steinert RF, Bayliss B, Brint SF, Giamporcaro JE, Hunkeler JD. Longterm clinical results of AMO PhacoFlex model SI-18 intraocular lens implantation. Journal of Cataract and Refractive Surgery. 1995;**21**(3):331-338. DOI: 10.1016/s0886-3350(13)80143-5

[108] Barrett GD, Constable IJ, Stewart AD. Clinical results of hydrogel lens implantation. Journal of Cataract and Refractive Surgery. 1986;**12**(6):623-631. DOI: 10.1016/ s0886-3350(86)80076-1

[109] Cionni RJ. Intraocular lenses to restore and preserve vision following cataract surgery. In: Kohnen T, Koch DD, editors. Cataract and Refractive Surgery. Essentials in Ophthalmology. Berlin, Heidelberg: Springer; 2006. DOI: 10.1007/3-540-30796-6\_1

[110] Werner L. Biocompatibility of intraocular lens materials. Current Opinion in Ophthalmology. 2008;**19**(1):41-49. DOI: 10.1097/ ICU.0b013e3282f20132

[111] Fichman RA. Use of topical anesthesia alone in cataract surgery. Journal of Cataract and Refractive Surgery. 1996;**22**(5):612-614. DOI: 10.1016/s0886-3350(96)80019-8

[112] Bille JF, Schanzlin D. Method for Removing Cataractous Material. US Patent US5246435A, 1993

[113] Nagy Z, Takacs A, Filkorn T, Sarayba M. Initial clinical evaluation of an intraocular femtosecond laser in cataract surgery. Journal of Refractive Surgery. 2009;**25**:1053-1060

[114] Gale RP, Saldana M, Johnston RL, Zuberbuhler B, McKibbin M. Benchmark standards for refractive outcomes after NHS cataract surgery. Eye (London, England). 2009;**23**(1):149-152. DOI: 10.1038/sj.eye.6702954

[115] Werner L. Intraocular lens evolution in the past 25 years as told by the journal of Cataract & Refractive Surgery. Journal of Cataract and Refractive Surgery. 2021;**47**(2):147-149. DOI: 10.1097/j. jcrs.0000000000000558

[116] Gundersen KG, Makari S, Ostenstad S, Potvin R. Retreatments after multifocal intraocular lens implantation: An analysis. Clinical Ophthalmology. 2016;**10**:365-371

[117] Makhotkina NY, Dugrain V, Purchase D, Berendschot T, Nuijts R. Effect of supplementary implantation of a sulcus-fxated intraocular lens in patients with negative dysphotopsia. Journal of Cataract and Refractive Surgery. 2018;**44**(2):209-218

[118] Makhotkina NY, Berendschot TT, Beckers HJ, Nuijts RM. Treatment of negative dysphotopsia with supplementary implantation of a sulcus-fixated intraocular lens. Graefe's Archive for Clinical and Experimental Ophthalmology. 2015;**253**(6):973-977 82 T.C.Y. Chan et al

[119] Falzon K, Stewart OG. Correction of undesirable pseudophakic refractive error with the Sulcofex intraocular lens. Journal of Refractive Surgery. 2012;**28**(9):614-619

[120] Zhou H, Zhu C, Xu W, Zhou F. The efficacy of accommodative versus monofocal intraocular lenses for cataract patients: A systematic

review and meta-analysis. Medicine. 2018;**97**(40):e12693

[121] Alio JL, Alio Del Barrio JL, Vega-Estrada A. Accommodative intraocular lenses: Where are we and where we are going. Eye and Vision. 2017;**4**:16. DOI: 10.1186/ s40662-017-0077-7

[122] FDA News Release. http://www. fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm511446.htm [Accessed: March 11, 2022]

[123] Akella SS, Juthani VV. Extended depth of focus intraocular lenses for presbyopia. Current Opinion in Ophthalmology. 2018;**29**(4):318-322

[124] Gallego AA, Bara S, Jaroszewicz Z, Kolodziejczyk A. Visual Strehl performance of IOL designs with extended depth of focus. Optometry and Vision Science. 2012;**89**(12):1702-1707

[125] Cochener B, Concerto Study G. Clinical outcomes of a new extended range of vision intraocular lens: International Multicenter concerto study. Journal of Cataract and Refractive Surgery. 2016;**42**(9):1268-1275

[126] Sandoval HP, Fernández de Castro LE, Vroman DT, Solomon KD. Comparison of visual outcomes, photopic contrast sensitivity, wavefront analysis, and patient satisfaction following cataract extraction and IOL implantation: Aspheric vs spherical acrylic lenses. Eye (London, England). 2008;**22**(12):1469- 1475. DOI: 10.1038/sj.eye.6702925

[127] Rocha KM, Soriano ES, Chalita MR, Yamada AC, Bottos K, Bottos J, et al. Wavefront analysis and contrast sensitivity of aspheric and spherical intraocular lenses: A randomized prospective study. American Journal of Ophthalmology. 2006;**142**:750-756

*Introductory Chapter: Refractive Surgery DOI: http://dx.doi.org/10.5772/intechopen.104578*

[128] Rocha KM, Soriano ES, Chamon W, Chalita MR, Nosé W. Spherical aberration and depth of focus in eyes implanted with aspheric and spherical intraocular lenses: A prospective randomized study. Ophthalmology. 2007;**114**(11):2050- 2054. DOI: 10.1016/j.ophtha.2007.01.024

[129] Werner L, Olson RJ, Mamalis N. New technology IOL optics. Ophthalmology Clinics of North America. 2006;**19**:469-483

[130] Du W, Lou W, Wu Q. Personalized aspheric intraocular lens implantation based on corneal spherical aberration: A review. International Journal of Ophthalmology. 2019;**12**(11):1788-1792. DOI: 10.18240/ijo.2019.11.19

[131] Braga-Mele R, Chang D, Dewey S, et al. ASCRS cataract clinical committee multifocal intraocular lenses: Relative indications and contraindications for implantation. Journal of Cataract and Refractive Surgery. 2014;**40**(2):313-322

[132] Schmickler S, Bautista CP, Goes F, Shah S, Wolffsohn JS. Clinical evaluation of a multifocal aspheric diffractive intraocular lens. The British Journal of Ophthalmology. 2013;**97**(12):1560-1564

[133] Lichtinger A, Rootman DS. Intraocular lenses for presbyopia correction: Past, present, and future. Current Opinion in Ophthalmology. 2012;**23**:40-46

[134] Montes-Mico R, Ferrer-Blasco T, Charman WN, Cervino A, Alfonso JF, Fernandez-Vega L. Optical quality of the eye after lens replacement with a pseudoaccommodating intraocular lens. Journal of Cataract and Refractive Surgery. 2008;**34**:763-768

[135] Kohnen T, Allen D, Boureau C, Dublineau P, Hartmann C, Mehdorn E, et al. European multicenter study of the AcrySof ReSTOR apodized diffractive intraocular lens. Ophthalmology. 2006;**113**:578-584

[136] Alio JL, Pinero DP, Plaza-Puche AB, Chan MJ. Visual outcomes and optical performance of a monofocal intraocular lens and a new-generation multifocal intraocular lens. Journal of Cataract and Refractive Surgery. 2011;**37**:241-250

[137] Rosen E, Alio JL, Dick HB, Dell S, Slade S. Efficacy and safety of multifocal intraocular lenses following cataract and refractive lens exchange: Metaanalysis of peer-reviewed publications. Journal of Cataract and Refractive Surgery. 2016;**42**:310-328

[138] Sudhir RR, Dey A, Bhattacharrya S, Bahulayan A. AcrySof IQ PanOptix intraocular Lens versus extended depth of focus intraocular Lens and trifocal intraocular Lens: A clinical overview. Asia-Pacific Journal of Ophthalmology (Phila). 2019;**8**(4):335-349. DOI: 10.1097/ APO.0000000000000253

[139] Kohnen T, Suryakumar R. Extended depth-of-focus technology in intraocular lenses. Journal of Cataract and Refractive Surgery. 2020;**46**(2):298-304. DOI: 10.1097/j.jcrs.0000000000000109

[140] Kohnen T, Böhm M, Hemkeppler E, Schönbrunn S, DeLorenzo N, Petermann K, et al. Visual performance of an extended depth of focus intraocular lens for treatment selection. Eye. 2019;**33**:1556-1563

[141] Bellucci R, Curatolo MC. A new extended depth of focus intraocular lens based on spherical aberration. Journal of Refractive Surgery. 2017;**33**(389-394):13

[142] Savini G, Balducci N, Carbonara C, et al. Functional assessment of a new extended depth-of-focus intraocular lens. Eye (London, England). 2019;**33**(3):404- 410. DOI: 10.1038/s41433-018-0221-1

[143] Dick HB, Elling M, Schultz T. Binocular and monocular implantation of small aperture intraocular lenses in cataract surgery. Journal of Refractive Surgery. 2018;**34**:629-631

[144] Studeny P, Krizova D, Urminsky J. Clinical experience with the WIOL-CF accommodative bioanalogic intraocular lens: Czech National Observational Registry. European Journal of Ophthalmology. 2016;**26**:230-235


**6. Organisms**

Alonso *et al.* [7] determined Hg contents in sediments and fish (*Eugerres plumieri* mojarra and *Mugil curema* mullet) in the CGSM.

*E. plumieri* is a resident species in the CGSM, a secondary consumer, predominantly of the bivalve *Mytilopsis sallei* that forms banks on the bottom of the swamp, a filter-feeding species, while the mullet (*M. incilis*) is purely detritivorous. In the first, the contents were always about twice as high as in the second. The highest contents corresponded to the samples at the beginning of the year, corresponding to the end of the dry season and the beginning of the rainy season. As mentioned for the bay of Cartagena, the contents in the two species were 7.3 times lower than in BC (**Table 2**).

Campos [12] made the first determinations of Hg in the oyster Crassostrea rhizophorae, in samples collected in January 1987 at two stations located in the northern fringe, one on the western side at the mouth of the Clarín channel that transports and discharges water from of the Magdalena River and the second in the eastern part of the strip, near the mouth of the CGSM in the sea. The contents fluctuated between 0.04 and 0.18 μg Hg g−1 p.s., the latter corresponding to the samples from the Clarín channel.

*The mean value and standard error are given. LOD Limit of detection (7.4 μg Hg g−1 d.w.).*

#### **Table 2.**

*Total mercury content (μg Hg g−1 d.w.) in two species of fish from the CGSM collected between March and November 1996.*

*Mercury in the Colombian Caribbean: The Bay of Cartagena, A Model in Resilience DOI: http://dx.doi.org/10.5772/intechopen.107240*

#### **Table 3.**

*Total mercury content (μg kg−1 fresh weight) in fish species from the CGSM collected between January and December 2018.*

Pinzón-Bedoya *et al.* [13] determined the concentrations of Hg (μg/kg f.w, fresh weight) contained in the muscle of fish species usually consumed by inhabitants of the area (**Table 3**). The compilation of the data shows that the results presented by Alonso *et al.* [7] an increase in the concentrations of Hg has been presented, which could demonstrate that the contributions of this metal persist, whether due to anthropic or natural origin, to the ecosystem; Likewise, it is possible to affirm the existence of accumulative and magnifying processes of Hg from the sediments to fish and bivalves.

Alonso *et al.* [7] indicated that the concentrations of Hg measured in the ecosystem components of the Ciénaga Grande de Santa Marta could be attributed to atmospheric deposition processes since this area did not present a significant industrial development. However, Caballero-Gallardo *et al.* [14] warn that the CGSM receives contaminants from intensive agriculture, especially bananas and African palm. Regardless of the source, the truth is that in the results of Pinzón-Bedoya *et al.* [13] Hg concentrations were positively correlated with morphometric variables (weight and length), evidencing Hg bioaccumulation processes in the aquatic biota of this ecosystem.


**Author details**

David G. Ashbrook\* and Lu Lu\* Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA

\*Address all correspondence to<EMAIL_ADDRESS>and<EMAIL_ADDRESS>
© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Recombinant Inbred Mice as Models for Experimental Precision Medicine and Biology DOI: http://dx.doi.org/10.5772/intechopen.96173*


**5. Concluding Remarks**

In this paper, a modification of the continuous symmetric-power distribution has been introduced. The particular case of the normal distribution the MPN distribution has been examined in detail. This distribution arises by modifying the distribution function of the symmetrical powers family. After carrying out this modification, a more flexible family of probability distributions is obtained, allowing for the kurtosis coefficient to take a certain range of values in the parameter space. For this model, its basic properties, different method of estimation and Fisher's information matrix were studied. By using a real dataset, we showed that the MPN distribution provides a better fit than other existing models in the literature such as the T S, SN , and PN distributions.

**Author Contributions:** The authors contributed equally to this work.

**Funding:** This work was partially completed while Héctor W. Gómez visited the Universidad de Las Palmas de Gran Canaria, supported by MINEDUC-UA project, code ANT1855. This research was also funded by (EGD) [Ministerio de Economía y Competitividad, Spain] grant number [ECO2013–47092]; (EGD)[Ministerio de Economía, Industria y Competitividad. Agencia Estatal de Investigación] grant number [ECO2017–85577–P ];

**Acknowledgments:** We also acknowledge the referee's suggestions that helped us to improve this work.

**Conflicts of Interest:** The authors declare no conflicts of interest.


**2.2. Data pre-processing**

The corpus was also used offline where it was analyzed using machine learning and spreadsheet tools during pre-processing, classification and the post processing of the data. A function built into RStudio was then used to remove unwanted characters, texts, punctuations and numbers from the text files created as a result of the extracted data from Twitter. After successfully searching Twitter and obtaining the number of tweets required, the tweets were 'cleaned' using RStudio's cleaning function.


**5. Acknowledgment**

This work was supported by the strategic grant **POSDRU/89/1.5/S/57649**, Project **ID-57649** (PERFORM-ERA), co-financed by the European Social Fund-Investing in People, within the Sectoral Operational Programme Human Resources Development 2007-2013 and by the **IDEAS Grant CNCSIS**, **1878/2008**, contract no. 1141/2009.


**5. References**

generally favourable. A high index of clinical suspicion is needed to diagnose this uncommon condition so that appropriate treatment can be initiated. Complications, in a short- and a long-term, include but are not limited to cognition and behavioural changes.

Atanassova, P. A. (2007). Antiphospholipid syndrome and vascular ischemic (occlusive)

Atanassova PA, et al. (2006). Abnormal ECG patterns during the acute phase of

Barinagarrementeria, F, Cantu, C, Arredondo, H. (1992). Aseptic cerebral venous

Bender A, Schulte-Altedorneburg G, Mayer T et al. (2007) Functional outcome after cerebral

Brown, W. R. and C. R. Thore (2011). Review: cerebral microvascular pathology in ageing

Buccino G, Scoditti U, Patteri I et al. (2003) Neurological and cognitive long-term outcome in

Cakmak S, Derex L, Berruyer M et al. (2003). Cerebral venous thrombosis: Clinical outcome and systematic screening of prothrombothic factors. *Neurology* 60: 1175-1178. Chang, Y. J., et al. (1995). Isolated cortical venous thrombosis--discrepancy between clinical features and neuroradiologic findings. A case report. *Angiology* 46(12): 1133-1138. Ciccone A, Canhão P, Falcão F, Ferro JM, Sterzi R. (2004). Thrombolysis for cerebral vein

De Bruijn SF, Budde M, Teunisse S *et al.* for the Cerebral Venous Sinus Thrombosis Study

De Bruijn SF, Haan RJ, Stam J. (2001). Clinical features and prognostic factors of cerebral

Dentali, F., Gianni, M., Crowther, M.A., Ageno, W. (2006). Natural history of cerebral vein

Ferro, J. M. (2010). Cerebral venous thrombosis. Presentation at 14th ESO Stroke Summer

Ferro JM, Correia M, Pontes C *et al*. for the Cerebral Venous Thrombosis Portuguese

venous sinus thrombosis. *Neurology* 54(8): 1687-1689.

thrombosis: a systematic review. *Blood* 108: 1129–1134.

Thrombosis in Portugal 1980–98. *Cerebrovasc Dis* 11: 177-182.

patients with cerebral venous sinus thrombosis. *Acta Neurologica Scandinavica*

and dural sinus thrombosis. *Cochrane Database of Systematic Reviews* Issue 1. Art.

Group. (2000). Long-term outcome of cognition and functional health after cerebral

venous thrombosis in a prospective series of 59 patients. *J Neurol Neurosurg*

School, Warsaw, Poland, 27 June – 3 July 2010 (last accessed on 13 July 2011 at http://www.skolamed.pl/img/panel/files/eso2010/pdf/FerroJ\_Cerebral\_venous

Collaborative Study Group (VENOPORT). (2001). Cerebral Vein and Dural Sinus

Bousser MG, Ferro JM. (2007). Cerebral venous thrombosis: an update. *Lancet* 6: 162-170. Breteau G, Mounier-Vehier F, Godefroy O *et al.* (2003). Cerebral venous thrombosis: 3-year

clinical outcome in 55 consecutive patients. *J Neurol* 250: 29-35.

and neurodegeneration. *Neuropathol Appl Neurobiol* 37(1): 56-74.

subarachnoid hemorrhage in patients without previous heart disease. *Central*

thrombosis: proposed prognostic scale. *Journal of Stroke and Cerebrovascular Disease*

diseases: an overview. *Yonsei Medical Journal* 48(6): 901-926.

*European Journal of Medicine* 1(2): 148-157.

venous thrombosis. *J Neurol*; 254:465-470.

**5. References**

2: 34-39.

107(5): 330-335.

No.: CD003693.

*Psychiatry*: 7*0*: 105-108.

\_thrombosis.pdf)

**9**

*Australia*

**Venous Thrombosis and the Eye**

Venous thrombosis is associated with Virchow's triad. This involves the combination of hypercoagulability, damage to the vessel endothelium and haemodynamic changes in the form of stasis or turbulence. These features ultimately contribute to thrombosis formation

Venous thrombosis can affect the eyes, resulting in serious ocular symptoms and is a significant cause of vision loss worldwide (Rogers, McIntosh et al. 2010). In the eye, venous thrombosis can result in a branch or a central retinal vein occlusion. The eye can also be affected by systemic venous thrombosis such as that which occurs in cerebral venous sinus thrombosis presenting with papilloedema, or in anti-phospholipid syndrome resulting in

In this chapter, we will discuss the ocular features of venous thrombosis, the presentation of retinal vein occlusion, and its ocular and systemic management. We will then examine the

Retinal venous obstruction occurs as a result of Virchow's triad in the retinal vessels with stasis, hypercoagulability and endothelial change. In the retina, disruption of venous return results in elevated intravascular pressure and culminates in retinal haemorrhage and oedema. Retinal ischaemia then follows, leading to non-perfusion of the capillary beds. Retinal vein occlusion RVO can be classified as either a branch retinal vein occlusion (BRVO) (Figure 1) or a central retinal vein occlusion (CRVO) (Figure 2) depending upon the location of the obstruction (Hayreh 2005). Each of BRVO and CRVO can be further sub-

Ischaemic RVO is characterised by retinal capillary non-perfusion and results in more severe signs and symptoms including significant decrease in visual acuity, cotton wool spots (indicating retinal ischaemia) and a relative afferent pupil defect. An ischemic RVO is

In non-ischaemic RVO stasis of the retinal veins occurs. There is leakage from the capillary bed but capillary perfusion is still present. A non-ischaemic RVO is associated with decreased visual acuity as a result of leaking retinal capillaries that cause macular

usually associated with ocular complications such as intraocular neovascularisation.

retinal arteriole occlusion, ischemic optic or cranial neuropathies.

ophthalmic manifestations of systemic venous thrombosis.

classified into ischaemic and non-ischaemic categories.

**1. Introduction**

**2. Retinal vein occlusion**

**2.1 Pathogenesis**

oedema.

(Heit 2008).

Bob Z. Wang and Celia S. Chen

*Flinders Medical Centre and Flinders University*

professionals from the American Heart Association/American Stroke Association. *Stroke* 42(4): 1158-1192.


**3. Effects of laser power**

Power is one of the most influential laser parameters when surface treating a material. Adjusting the power increases the surface irregularities of the material and therefore enhan‐ ces the topography properties of the substrate [25, 33]. In this chapter, the effects of four different powers on surface topographic and oxidation properties of titanium substrates are investigated, and the bioactivity of the treated substrates is examined through the use of simulated body fluid (SBF). Simulated body fluid (SBF), or formally known as hydroxyapa‐ tite, is a supersaturated insoluble calcium phosphate mineral, with the chemical composition of Ca10(PO4)6(OH)2. This fluid has a close similarity with human blood plasma and is the essential component of the biological hard tissues such as bones. Due to the high absorbance and catalytic properties of SBF, this fluid is commonly used to estimate the biocompatibility level of materials used in implant productions.

To treat the titanium substrates, a range of low to high average laser powers from 6 to 12W was used, while frequency and scanning speeds were kept constant in all cases. The effec‐ tive number of pulses for all results was kept constant to be 25 pulses for frequency of 100 kHz [36, 37]. **Table 1** introduces the parameters used in more detail.

**Table 1.** Laser parameters used in surface treating of Ti substrates.

#### **3.1. Surface topography analysis**

increases the wettability of surface of the material. Consequently, this leads to an increase in the apatite‐inducing ability of the material and greatly improves the biocompatibility of the

The nanosecond laser used for obtaining all the results discussed in this chapter was a Nd:YAG pulsed laser system (SOL‐20 by Bright Solutions Inc). The maximum output power is 20 W with a wavelength of 1064 nm and a repetition rate ranging between 10 and 100 kHz. This laser emits pulses of 6–35 ns pulse duration. The diameter of circular output beam from the laser is around 9 mm. The diameter of beam is reduced to 8mm by using an iris diaphragm before entering to galvo‐scanner. A two‐axis galvo‐scanner (JD2204 by Sino Galvo) with the input aperture of 10 mm and beam displacement of 13.4 mm was used for beam scanning since it has a high scanning speed (to 3000 mm/s). In order to focus the normal beam to the surface of Ti, scan lens of a focal length of 63.5 mm was used. The theoretical focused laser spot diame‐ ter (*d*0) is calculated to be 20 μm. During the experiment, the spot size may be bigger due to scatter and misalignment. The average laser fluence was 900 μJ at the frequency of 10 kHz.

The scanning parameters including scanning speed, and scanning configurations can be adjusted through the software operating the laser. When the combination of parameters is adjusted with this software, along with power and frequency set for laser irradiation, the

Power is one of the most influential laser parameters when surface treating a material. Adjusting the power increases the surface irregularities of the material and therefore enhan‐ ces the topography properties of the substrate [25, 33]. In this chapter, the effects of four different powers on surface topographic and oxidation properties of titanium substrates are investigated, and the bioactivity of the treated substrates is examined through the use of simulated body fluid (SBF). Simulated body fluid (SBF), or formally known as hydroxyapa‐ tite, is a supersaturated insoluble calcium phosphate mineral, with the chemical composition of Ca10(PO4)6(OH)2. This fluid has a close similarity with human blood plasma and is the essential component of the biological hard tissues such as bones. Due to the high absorbance and catalytic properties of SBF, this fluid is commonly used to estimate the biocompatibility

To treat the titanium substrates, a range of low to high average laser powers from 6 to 12W was used, while frequency and scanning speeds were kept constant in all cases. The effec‐ tive number of pulses for all results was kept constant to be 25 pulses for frequency of 100

desired pattern is irradiated across the surface of the selected material.

implant surfaces [30–35].

358 360High Energy and Short Pulse Lasers

**3. Effects of laser power**

level of materials used in implant productions.

kHz [36, 37]. **Table 1** introduces the parameters used in more detail.

**2.1. Laser system**

Once treated, there is often more available exposed surface area of the material because of the increase in surface roughness, which, in return, enhances the apatite‐inducing ability and cell adhesion rate of that material. **Figure 1** displays the variation in the treated substrates using the stated powers.

**Figure 1.** Surface of treated titanium (A) 6 W, (B) 8 W, (C) 10 W, (D) 12 W.

Although the number of pulses delivered to each of these substrates is the same, as indicat‐ ed in **Table 1**, the images shown in **Figure 1** clearly indicate different surface topography after laser treatment. With an increase in power, the energy delivered to the surface of the materi‐ al increases as well, hence, more ablation and topography changes occur. Substrates treated with a power of 12 W have a larger surface affected by laser irradiation as opposed to 6 W.

During laser irradiation, a plasma plume with radial surface tension is formed surrounding the irradiated area due to the high temperature gradient caused by laser energy transfer. Immediately following irradiation, a high temperature difference exists between the surface of the material and the generated plasma plume. Thus, a high cooling rate results, which causes rapid re‐solidification of the ablated material. Consequently, the tension within the laser plume causes shooting of the molten titanium to outside of the ablated zones [37]. The micro re‐ solidified particles observed outside the crater in **Figure 1** have been formed due to the same reason.

Using 3D microscopy, the surface profile of the treated substrates can be compared; this is introduced in **Figure 2**. This study used the Zeta‐20 optical profiler to scan the surface of the samples in order to obtain the surface topography results across each sample.

**Figure 2.** Surface profiles of Ti (A) 6 W, (B) 8 W, (C) 10 W, (D) 12 W.

As shown, an increase in laser power clearly affects the surface topography profile of titanium substrates. Different laser powers create different surface irregularities across the surface of the treated titanium substrates.

#### **3.2. Surface temperature analysis**

Different power levels deliver various amounts of energy to the surface of the substrate, and, therefore, increase the surface temperature of the titanium. This increase in the surface temperature could affect the surface structure, topographic properties, and oxidation of the titanium substrates. Oxidation is an important factor when considering bioactivity of a material. With higher oxidation, a higher surface energy is present, which results in more interaction between the implant and the body. Therefore, generating larger amounts of titanium oxide across the surface substrates consequently increases the biocompatibility of the treated work pieces. However, after a certain power threshold, the energy delivered to the surface of the titanium increases the surface temperature beyond the oxidation limit. Therefore, the material develops less titanium oxide as the surface undergoes larger ablation [32, 34, 38].

In order to calculate the surface temperature in this chapter, a theoretical calculation has been conducted according to the previous published results [25, 36, 39]; in this method, we assumed that the laser energy is absorbed in a much thinner layer compared to the penetration depth of the heat wave. Finally, the average surface temperature of the Ti substrate can be ob‐ tained as fully discussed in [25, 39]:

$$T\_n = 2\alpha \frac{\left[1 - \frac{2}{3}\alpha\right]}{(1 + \alpha^2)} \frac{T\_n}{(1 - \alpha)} \left[1 + \frac{\alpha^n - \alpha}{n(1 - \alpha)}\right] \tag{1}$$

where *T*m is the maximum temperature calculated at the end of first pulse, *n* is the pulse numbers, and α is the constant ratio for the previous maximum and the following minimum temperatures and equal to α = (*t*p/*t*pp)1/2, where *t*pp is the pulse interval and equal to *t*pp *=* 1*/f* (*f* is pulse repetition rate) and *t*p is pulse duration. The analytical results obtained in this study are associated with possible errors due to multiple assumptions made throughout the study.

Upon completion of the analytical analysis, the temperature profile for both cases with 8 and 10 W powers, and a pulse number range of 2 pulses to 50 pulses is obtained.

The trend of average surface temperature of the treated titanium substrates is shown in **Figure 3**.

**Figure 3.** Maximum average surface temperature in each power.

causes shooting of the molten titanium to outside of the ablated zones [37]. The micro re‐ solidified particles observed outside the crater in **Figure 1** have been formed due to the same

Using 3D microscopy, the surface profile of the treated substrates can be compared; this is introduced in **Figure 2**. This study used the Zeta‐20 optical profiler to scan the surface of the

As shown, an increase in laser power clearly affects the surface topography profile of titanium substrates. Different laser powers create different surface irregularities across the surface of

Different power levels deliver various amounts of energy to the surface of the substrate, and, therefore, increase the surface temperature of the titanium. This increase in the surface temperature could affect the surface structure, topographic properties, and oxidation of the titanium substrates. Oxidation is an important factor when considering bioactivity of a material. With higher oxidation, a higher surface energy is present, which results in more interaction between the implant and the body. Therefore, generating larger amounts of titanium oxide across the surface substrates consequently increases the biocompatibility of the treated work pieces. However, after a certain power threshold, the energy delivered to the surface of the titanium increases the surface temperature beyond the oxidation limit. Therefore, the material develops less titanium oxide as the surface undergoes larger ablation [32, 34, 38].

samples in order to obtain the surface topography results across each sample.

**Figure 2.** Surface profiles of Ti (A) 6 W, (B) 8 W, (C) 10 W, (D) 12 W.

the treated titanium substrates.

**3.2. Surface temperature analysis**

reason.

360 362High Energy and Short Pulse Lasers

As evident, with 12 W of power, the maximum average surface temperature of the titanium exceeds its evaporation point, and therefore less concentration of titanium oxide is generat‐ ed along the surface of the substrates. Also, more ablation occurs, which agrees with the observations. Having a larger concentration of titanium oxide across the surface results in better cell interactions. To further investigate the oxidation of treated substrates, energy dispersive X‐ray (EDX) analysis was conducted to detect the amount of oxygen available across the surface of substrates treated using the stated powers.

#### **Figure 4** indicates the results.

**Figure 4.** EDX analysis of the irradiated Ti at 6, 8, 10, and 12 W.

Comparing the trace of oxygen across the surface of all four substrates, it is observed that with an increase in power, the oxygen concentration increases slightly as well, until a power of 12 W is reached, which shows slightly a lower trace of oxygen. This is in agreement with the average temperature results observed in **Figure 3**. Considering the results shown in **Figures 4** and **5**, it is expected that powers of 8 and 10 W would result in a better biocompatibility compared to othertwo powers. This conclusion is assessed through the use of simulated bodily fluids (SBF).

**Figure 5.** SBF‐soaked substrates. (A) 8 W, (B) 10 W.

#### **3.3. Biocompatibility assessment**

**Figure 4** indicates the results.

362 364High Energy and Short Pulse Lasers

**Figure 4.** EDX analysis of the irradiated Ti at 6, 8, 10, and 12 W.

**Figure 5.** SBF‐soaked substrates. (A) 8 W, (B) 10 W.

fluids (SBF).

Comparing the trace of oxygen across the surface of all four substrates, it is observed that with an increase in power, the oxygen concentration increases slightly as well, until a power of 12 W is reached, which shows slightly a lower trace of oxygen. This is in agreement with the average temperature results observed in **Figure 3**. Considering the results shown in **Figures 4** and **5**, it is expected that powers of 8 and 10 W would result in a better biocompatibility compared to othertwo powers. This conclusion is assessed through the use of simulated bodily

To determine how the differences in surface topography affect the biocompatibility of titanium, the treated substrates using powers of 8 and 10 W were immersed in SBF for 7 days. **Figure 5** shows the scanning electron microscopy (SEM) photographs of the substrates after the completion of the assessment.

In **Figure 5**, the white layers across the induced line patterns indicate the bone‐like apatite deposition on the surface of the titanium. These microscopy images show that generally with an increase in power, apatite‐inducing ability across the surface of treated titanium increases as well. Looking closely into **Figure 5**, the EDX results for 10 W curve indicate a larger amount of apatite deposition compared to the 8 W curve. This is further observed in the EDX analy‐ sis conducted on these titanium substrates shown in **Figure 6**. Detecting larger amount of oxygen, calcium, and phosphorous elements indicates a higher apatite‐inducing ability forthe substrates.

**Figure 6.** EDX analysis at 8 and 10 W.

As shown, the apatite‐inducing ability of substrates treated with a power of 10 W is higher than the substrates treated with 8 W. This is in agreement with results observed with oxida‐ tion and SEM photography analysis.

Overall, the biocompatibility was highest for substrates treated with 10 W. This power provides adequate surface topography and the energy delivered is within the oxidation temperature range, hence creating a desirable environment for cell attachment to take place.


**Synthesis of Nanostructured Materials for Storing Hydrogen as an Alternative Source to Fossil Fuel Derivatives**

Omar Reyes-Martínez and José Luis Velázquez Ortega

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61076

### **Abstract**

The decline in global reserves of fossil fuels due to the increasing energy demand has caused the petrochemical industry to be interested in finding new energy sources. An alternative that should be considered is the technology based on hydrogen as it is friendly to the environment and its combustion is greenhouse.

The technology based on hydrogen considers the synthesis of metal-organic materials that have the ability to store, although this phenomenon (storage) is one of the biggest problems to overcome. For this reason, options synthesized for storing materials are provided in this chapter of Book Two. These materials are considered nanostructured systems with specific features in 2D and 3D. The synthesized materials are tetracyanoniquelates ( [M (H2O)2 (Ni (CN)4) (H2O)n M = manganese, cobalt, and nickel) and hexacyano-cobaltates ((M3 [Co (CN) 6] 2xH2O); M: manganese, nickel, cobalt, zinc, cadmium, and copper), both systems with individual cavities that require study and characterization. Moreover, in this chapter, a thermogravimetric characterization is performed in order to establish the activation energy of the mobility of water molecules contained in the cavities, relevant information to establish the energy barrier to overcome in the storage of hydrogen.

**Keywords:** Fossil fuel, hydrogen, nanoporous, thermogravimetry, activation energy

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


**Author details**

Michael Schuliga\*

Address all correspondence to<EMAIL_ADDRESS>
Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia


**4. Discussion**

Polystyrene μPs were successfully biofunctionalized with an anti-HER2 antibody or with a secondary antibody, as demonstrated by the detection of fluorescence under a microscope and by changes in their ζ-potential. The reduction in μPs electronegativity could help in their interaction with the plasma membrane, which contains negatively charged saccharides. In fact, it has been described that positively or slightly negatively charged particle surfaces favor cell intake [14,33–35].

The cell lines used in this study are isogenic breast epithelial cell lines. D492 was established by isolating suprabasal cells from a reduction mammoplasty and subsequently immortalizing them using the *E6* and *E7* oncogenes from the human papilloma virus [30,31]. D492 has stem cell properties evaluated by the ability to generate luminal and myoepithelial cells and, in 3D culture, to form branching ductal–alveolar-like structures. D492HER2 was generated by overexpressing the HER2 oncogene in D492 [32]. Interestingly, D492 showed higher percentages of μPs internalization than D492HER2. A possible explanation could be the differences in phenotype between these cells. D492HER2 cells undergo an epithelial to mesenchymal transition (EMT) and express mesenchymal markers, which could reduce their ability to internalize μPs [31,32]. Higher rates of μP internalization have also been described in MCF10A breast epithelial normal cells than in SKBR3 breast epithelial tumoral cells, which also overexpress HER2 [14].

The molecules used to bio-functionalize the μPs also influenced the internalization rates. For both cell lines, the percentage of cells with internalized μP-antiH was higher than that of cells with internalized μP-secAb. This result was expected, since we hypothesized that a specific recognition between the cells and the μPs, such as that afforded by antiH biofunctionalization, could result in an increase in μP internalization. Also as expected, the increase in the percentages of μPs internalization obtained with antiH biofunctionalization was higher for D492HER2 cells, which overexpress HER2, than for D492 cells, which express HER2 at much lower levels [32]. These results clearly indicate that when μPs are biofunctionalized with molecules that specifically interact with plasma membrane receptors, their internalization can be improved, and the level of improvement is related to the number of receptors that are present on the cell surface.

Finally, in relation to the culture conditions, our results indicate that the percentage of cells with internalized μPs clearly decreased in fluidic conditions compared with static conditions. This was probably because the establishment of prior transient contacts between the plasma membrane and the μPs may be more difficult in fluidic conditions or in high shear stress conditions [36,37]. One can hypothesize that in the case of dynamic cultures, specific targeting may be helpful to improve the internalization rates, as it may facilitate the frequency and strength of μPs-cell contacts. Our results agree with this hypothesis because, for both cell lines, the increase of μPs-antiH internalization was higher in fluidic than in static cocultures when compared with μPs-secAb internalization, which opens the door to scale-up studies.

The present results, together with previous research, emphasize the relevance of cell type, specific targeting, and culture conditions such as mono- or cocultures and static or fluidic, to the potential application of NPs and μPs for drug delivery to cancer cells.


# **Feasible, Robust and Reliable Automation and Control for Autonomous Systems**

Edited by Umar Zakir Abdul Hamid, Argyrios Zolotas and Chuan Hu Printed Edition of the Special Issue Published in *Electronics*

www.mdpi.com/journal/electronics

## **Feasible, Robust and Reliable Automation and Control for Autonomous Systems**


*2.1. Study Population*

A total of 53 traffic volunteers were recruited for this study. Prior to the study, approval for the study was taken from the institutional review board at the University of Massachusetts, Amherst and Nepal Health Research Council, Nepal. Permission to carry out the study was also completed from the government of Nepal. A total of 36 traffic volunteers participated in air pollution exposure study in the spring season, and 30 traffic volunteers participated in the summer season, though not all subjects consented to provide blood samples, where 33 volunteers permitted blood samples in spring, and 29 volunteers permitted blood samples in summer. These samples were from 29 men and 4 women in spring, and 25 men and 4 women in summer. From the subjects who volunteered to provide blood samples, there were 13 smokers and 14 non-smokers in the spring season and there were 9 smokers and 21 non-smokers in the summer season. All the subjects were prescreened for their medical history of asthma, serious respiratory or heart diseases, tuberculosis, and diabetes, and these were used as exclusion criteria for participation in this study. Descriptive statistics of subject demographics are given in Table 1.

1 Based on subject samples in spring (*n* = 33) and summer (*n* = 29); 2 24-hour average; 3 Passive sampling data are the one-week mean concentration from five sites [39]. 4 *p*-values are the results of two-sided independent *t*-tests.


**Author details**

**Section/topic # Checklist item Reported on**

of studies, if done, including measures of consistency (e.g., I2

the cumulative evidence (e.g., publication bias, selective

or subgroup analyses, meta-regression), if done, indicating

included in the review, with reasons for exclusions at each

extracted (e.g., study size, PICOS, follow-up period) and

each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally

confidence intervals and measures of consistency.

subgroup analyses, meta-regression [see Item 16]).

evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy

of bias), and at review-level (e.g., incomplete retrieval of

of other evidence, and implications for future research.

other support (e.g., supply of data); role of funders for the

From: Moher et al. [50]. For more information, visit: www.prisma-statement.org. NR: not reported. NA: not applicable.

Synthesis of results 14 Describe the methods of handling data and combining results

for each meta-analysis.

reporting within studies).

which were pre-specified.

Study selection 17 Give numbers of studies screened, assessed for eligibility, and

Study characteristics 18 For each study, present characteristics for which data were

provide the citations.

Risk of bias within studies 19 Present data on risk of bias of each study and, if available,

Results of individual studies 20 For all outcomes considered (benefits or harms), present, for

Risk of bias across studies 22 Present results of any assessment of risk of bias across studies

Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or

Summary of evidence 24 Summarize the main findings including the strength of

Limitations 25 Discuss limitations at study and outcome level (e.g., risk

Conclusions 26 Provide a general interpretation of the results in the context

Funding 27 Describe sources of funding for the systematic review and

systematic review.

identified research, reporting bias).

makers).

with a forest plot.

Synthesis of results 21 Present results of each meta-analysis done, including

(see Item 15).

stage, ideally with a flow diagram.

any outcome level assessment (see item 12).

Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity

**RESULTS**

66 Socialization - A Multidimensional Perspective

**DISCUSSION**

**FUNDING**

Risk of bias across studies 15 Specify any assessment of risk of bias that may affect

**page #**

4

4

4

4, 5

4, 5

4, 5

4, 5

NR

5–8

5–8

4, 10 S1 Appendix

8–10

NA

10, S1 Appendix

)

Senay Kocakoyun1 \* and Fezile Ozdamli2

\*Address all correspondence to<EMAIL_ADDRESS>
1 Anadolu BIL Vocational School of Higher Education, Computer Programming Department, Istanbul Aydin University, Istanbul, Turkey

2 Computer Education and Instructional Technology (CEIT) Department, Near East University, Northern Cyprus