Accommodating intraocular lenses: a review of ... - Wiley Online Library

C L I N I C A L

A N D

E X P E R I M E N T A L

OPTOMETRY cxo_532

441..452

REVIEW

Accommodating intraocular lenses: a review of design concepts, usage and assessment methods Clin Exp Optom 2010; 93: 6: 441–452 Amy L Sheppard BSc MCOptom Abar Bashir BSc MCOptom James S Wolffsohn PhD MCOptom FAAO Leon N Davies PhD MCOptom FAAO Aston University, Birmingham, United Kingdom E-mail: [email protected]

Submitted: 30 March 2010 Revised: 29 July 2010 Accepted for publication: 3 August 2010

DOI:10.1111/j.1444-0938.2010.00532.x The correction of presbyopia and restoration of true accommodative function to the ageing eye is the focus of much ongoing research and clinical work. A range of accommodating intraocular lenses (AIOLs) implanted during cataract surgery has been developed and they are designed to change either their position or shape in response to ciliary muscle contraction to generate an increase in dioptric power. Two main design concepts exist. First, axial shift concepts rely on anterior axial movement of one or two optics creating accommodative ability. Second, curvature change designs are designed to provide significant amplitudes of accommodation with little physical displacement. Single-optic devices have been used most widely, although the true accommodative ability provided by forward shift of the optic appears limited and recent findings indicate that alternative factors such as flexing of the optic to alter ocular aberrations may be responsible for the enhanced near vision reported in published studies. Techniques for analysing the performance of AIOLs have not been standardised and clinical studies have reported findings using a wide range of both subjective and objective methods, making it difficult to gauge the success of these implants. There is a need for longitudinal studies using objective methods to assess long-term performance of AIOLs and to determine if true accommodation is restored by the designs available. While dual-optic and curvature change IOLs are designed to provide greater amplitudes of accommodation than is possible with single-optic devices, several of these implants are in the early stages of development and require significant further work before human use is possible. A number of challenges remain and must be addressed before the ultimate goal of restoring youthful levels of accommodation to the presbyopic eye can be achieved.

Key words: accommodation, ciliary body, intraocular lenses, lens capsule, presbyopia

Cataract surgery with intraocular lens (IOL) implantation has become a routine surgical procedure, with a treatment rate of 4,000 to 6,000 operations per million population each year in economically well-developed countries.1,2 A foldable, monofocal IOL is generally implanted into the capsular bag following liquefac-

tion and aspiration of the opacified lens mass. Post-operatively, fibrosis and contraction of the capsule result in firm fixation of the implant within the capsular bag. Progress in IOL materials and design, use of advanced pre-operative biometry and small incision procedures have allowed near-emmetropic distance

© 2010 The Authors Clinical and Experimental Optometry © 2010 Optometrists Association Australia

refractions to be achievable in the majority of cases.3–5 Problematic refractive errors, including high levels of astigmatism may also be successfully treated with cataract surgery or refractive lens exchange (RLE). Despite such significant accomplishments since IOLs were pioneered 60 years ago, the management of

Clinical and Experimental Optometry 93.6 November 2010

441

Accommodating intraocular lenses Sheppard, Bashir, Wolffsohn and Davies

presbyopia remains a challenge for modern surgeons and researchers alike. Potentially-accommodating IOLs (AIOLs) that are able to change either their position or shape in response to ciliary muscle contraction are at the forefront of much ongoing research attempting to restore true accommodative function to presbyopic eyes.5–7 Accommodation is the dynamic change in the refractive power of the eye to focus on objects at different distances8 and is governed by ciliary muscle contraction. The widely-accepted Helmholtzian theory9 states that as the ciliary muscle contracts, the majority of its mass shifts anteriorly and crucially, inwards, to reduce the diameter of the ciliary muscle collar,10,11 relaxing tension on the zonular fibres and allowing the elastic capsule to mould the lens into a more convex and dioptrically powerful form.6,12 The inevitable decline in accommodative amplitude and symptomatic loss of near visual function with age is termed presbyopia. Although the development of presbyopia is not fully understood, the majority of available evidence suggests that lenticular processes are of key significance.6,13 The continued growth of the lens throughout life,11,14,15 affecting its geometrical relationship with the surrounding zonules16,17 and ciliary body,18 coupled with changes in the elastic properties of the lens19,20 and capsule21 with age are implicated. Despite the complete loss of accommodative ability by the age of 55 years,22 recent in vitro23 and in vivo studies using ultrasonic biomicroscopy24,25 and high-resolution magnetic resonance imaging (MRI)11,26 have demonstrated that the human ciliary muscle maintains its contractile ability well into old age, even in pseudophakic subjects.26 While it is generally accepted that pseudophakic eyes are incapable of accommodation, some patients achieve remarkably good uncorrected near and distance vision following surgery and are independent of spectacles. The phenomenon of functional near vision in distancecorrected presbyopic eyes is termed pseudoaccommodation27,28 or apparent accommodation,29,30 and occurs due to a summation of non-accommodative influ-

ences including pupillary constriction leading to increased depth-of-field;31 lowmagnitude myopia32 or against-the-rule myopic astigmatism33,34 and higher-order ocular aberrations, particularly spherical aberration and coma.35 A range of surgical techniques are available to provide functional near vision in presbyopic eyes. Permanent monovision may be achieved through refractive lens exchange or corneal refractive surgery, however, this approach can result in compromised binocular function and may also necessitate a prolonged adaptation period.36,37 Zonal photorefractive keratectomy,38 decentred laser in situ keratomileusis39 and implantation of corneal inlays40 represent more experimental methods targeted at the cornea. Multifocal IOLs based on either diffractive optics or zones of varying refractive power, divide incoming light into two or more focal points and allow up to 50 per cent of patients to attain spectacle independence,41 however, due to their design, multifocal implants are frequently associated with poorer contrast sensitivity than monofocal IOLs42–44 and an increased incidence of troublesome visual phenomena including glare and halos.45,46 To avoid such disturbing visual effects and restore natural accommodative function, the ultimate goal in ongoing AIOL and presbyopia research is to refill the capsular bag with a substance able to mimic the behaviour of the youthful lens mass.5,47,48 To date, elastic polymers48,49 and fluid filled balloons50 have been trialled in animal eyes but not yet in humans in vivo. Problems such as severe capsular opacification, difficulties removing the lens contents through a small capsulorhexis, plugging of the capsulorhexis following polymer injection, unpredictable post-surgical refractive error and low amplitude of accommodation compared to the pre-operative state have yet to be overcome and it is likely that further years of laboratory and animal investigations are required before human use is plausible.51 AIOLs represent the only approach currently available for human use that aims to restore true accommodative function to presbyopic eyes by targeting the stiffened lens mass. AIOL implantation requires


442

surgical techniques similar to those of cataract surgery, thus making it repeatable with a high success rate in terms of the surgery itself, while outcomes can be more easily predicted. As we will see later, current AIOLs also include square-edged designs that limit capsular opacification. A range of AIOL designs are in use or undergoing developmental work. Singleoptic devices have been designed to use anterior axial movement of the optic with accommodative effort. The optic-shift principle was initially observed and further developed from the late 1980s by Dr Stewart Cumming, who measured an anterior movement of the optic with ciliary muscle contraction in a number of patients implanted with monofocal platestyle silicone IOLs, allowing for good intermediate and near vision in distancecorrected eyes.52 Dual-optic implants attempt to increase the possible dioptric power change with accommodative effort. Such AIOLs comprise a stationary minuspowered posterior optic connected to a high-powered and mobile positive anterior optic, which shifts forwards with ciliary muscle contraction. Further concepts for AIOLs include curvature-change devices to generate significant power change with minimal physical displacement and magnetically-driven active-shift implants that use small, repulsing magnets to drive the optic and capsule anteriorly during accommodation. Before examining the published literature on these lenses, it is important to consider how accommodative ability can be assessed. MEASUREMENT OF PSEUDOPHAKIC ACCOMMODATION AND DETERMINING SUCCESS WITH AIOLS To establish the level of success with any design of AIOL, it is important to employ objective means of assessment to identify the refractive and biometric changes that occur with accommodative effort. Subjective techniques alone, for example, reading acuity, amplitude of accommodation based on patient perception of blur and defocus curve determination are not sufficient to identify true accommodation. © 2010 The Authors

Clinical and Experimental Optometry © 2010 Optometrists Association Australia


Push-up accommodation measurement is known to overestimate the true amplitude of the response53 and can imply that active accommodation is occurring when it is not.54,55 Although subjective testing is of use in investigating patient satisfaction, such methods do not differentiate between pseudoaccommodation and true accommodation and may also be affected by patient and practitioner motivation. Objective attempts to evaluate the dynamic performance of implanted AIOLs have included retinoscopy,56,57 aberrometry35,58,59 and autorefraction,59 in addition to analysis of optic movement.60,61

Objective measurement of dioptric power change While direct measurement of refractive change in response to an accommodative stimulus may appear to be the optimum method for determining AIOL success, there are controversies associated with the available methods. Retinoscopy is typically considered an objective form of assessment62,63 and allows direct visualisation of dioptric power changes, although the traditional, manual procedure relies on subjective interpretation of the reflex by the practitioner, which may lead to poor reproducibility of results.64,65 The technique of photoretinoscopy (for example, PowerRefractor, PlusOptix, Nuremburg, Germany) can provide fully-objective measures of refraction in both eyes simultaneously, however instrument calibration is required for each subject.66,67 Autorefractors are widely used in both clinical and research settings and provide rapid, objective measures of refraction,68–70 although evaluation of pseudophakic accommodation may not prove straightforward. Senile pupillary miosis, coupled with accommodative constriction requires devices to be capable of measurement through very small pupils. Typical minimum pupil diameters specified by manufacturers range from 2.3 mm (for example, ShunNippon NVision-K5001/Grand Seiko WR-5100K and grand Seiko Auto Ref/ Keratometer WAM 5500) to 2.9 mm (Shin-Nippon SRW-5000/Grand Seiko WV-500).69 Several authors have questioned the application of autorefractors in

AIOL research5,47 due to difficulties in data capture associated with miotic pupils68,71 and the sub-prime optical quality of the eye caused by bright Purkinje images from the anterior optic surface, and the likely presence of some level of posterior capsular opacification. Wolffsohn and colleagues59 were able to measure static objective refractive change and record the objective accommodative response through undilated pupils in a cohort of mainly elderly subjects, using a commercially-available open-view autorefractor (Shin-Nippon SRW-5000). They found the static objective accommodation averaged +0.72 ⫾ 0.38 D (range 0.17 to 1.16 D). Continuous recording of accommodation may be useful in evaluating the accommodative dynamics of eyes implanted with AIOLs. Aberrometry, based on the Hartmann-Shack principle, for example, in which the shape of the wavefront resulting from a laser beam reflected by the retinal surface is described,72,73 allowing the spherocylindical refraction to be derived, represents a further possible technique for objective analysis of patients implanted with AIOLs. To date, very few AIOL studies have employed aberrometry.35,58 Using an aberrometer in AIOL assessment enables in vivo measurement of higherorder aberrations. As we will see, aberrations can play a significant role in postoperative vision. Despite the advantages of being both objective and observerindependent, aberrometers are generally not open-view and therefore, may be affected by instrument myopia. Additionally, the accuracy and reproducibility of aberrometry-derived refractive results have been questioned.74,75

Analysis of optic movement Rather than measurement of the refractive state of eyes implanted with AIOLs, assessment of changes in anterior chamber depth (ACD) with ciliary muscle contraction may be used as an indicator of accommodative ability.76 Several biometric techniques have been employed including high frequency ultrasonic biomicroscopy,77 partial coherence interferometry,60,78,79 Scheimpflug imaging using the


IOLMaster (Carl Zeiss, Jena, Germany)28,80 and anterior segment optical coherence tomography (AS-OCT).81 Furthermore, a new optical low coherence reflectometry device is now available (LenStar, HaagStreit or Allegro Biograph, Wavelight)82,83 that can measure lens position to a resolution of 0.01 mm. While these methods can accurately determine the axial shift of an optic, they do not provide a direct measurement of the change in refractive power of the eye. The following simple formula84 provides an approximation of the change in conjugation power of a system with movement of an optic:

ΔDc ≈ (Dm 13) Δs

(1)

where DDc is the change in power of the eye, Dm is the power (D) of the moving lens, and Ds is the change in lens position (mm). The formula indicates that an anterior optic shift of approximately 0.67 mm is necessary to produce a one dioptre accommodative response when using a single-optic of 19.00 D and a cornea with anterior and posterior radii of curvatures of 7.8 mm and 6.5 mm, respectively, and a corneal thickness of 0.55 mm. To induce accommodation and analyse the axial movement of the AIOL optic, most published studies have relied on pharmacological stimulation of the ciliary muscle, generally by topical application of 2% pilocarpine. The advantage of pharmacological rather than stimulus-driven accommodation is that patient compliance in fixating an accommodative stimulus is not required.85 The resultant powerful ciliary muscle contraction is accompanied by pronounced pupil miosis, hindering attempts to measure objective refractive changes.86 Furthermore, pilocarpine appears to act as a ‘superstimulus’ to accommodation.60 The axial movement of an implanted opticshift AIOL (1CU; HumanOptics AG, Irlangen, Germany) in response to a near stimulus has been compared with the movement following pilocarpine-induced accommodation.85,87 Minimal, clinically non-significant anterior movements occurred in response to the near stimulus (for example, -0.010 ⫾ 0.025 mm),85 whereas the forward shifts following


443


topical pilocarpine were approximately 20 times greater (for example, -0.201 ⫾ 0.127 mm).85 It is clear that powerful pilocarpine-induced ciliary muscle contraction does not represent the normal physiologic response.85,87,88 Pilocarpine instillation may be of more value in evaluating the maximum potential accommodative ability of an AIOL rather than its typical performance. Thus, the ideal evaluation of implanted AIOLs would include objective measures of refractive and biometric changes, preferably without instillation of pharmacological agents, to prove the existence of true pseudophakic accommodation.47,77,86 Subjective measures are important in terms of clinical outcome but cannot be relied on in isolation. To date, published studies have tended to report subjective findings alone or have used pilocarpine to stimulate accommodation for objective measures. There is a paucity of literature reporting objective changes in refraction and AIOL position in stimulus-driven accommodation. There is a need for objective techniques to be standardised to allow widespread use and acceptance.6,47,89 CURRENT AIOL DESIGN CONCEPTS

Single-optic devices Commercially available AIOLs are based on the optic-shift principle, relying on an anterior movement of the lens optic with ciliary muscle contraction to generate an increase in refractive power, although the precise mechanisms of action do vary between designs. The first AIOL to be marketed was the BioComFold 43A (Morcher GmbH, Stuttgart, Germany) in 1996, although to date, only one device, the Crystalens (Bausch & Lomb, Rochester, New York, USA), has received Food and Drug Administration (FDA) approval in the United States. The Crystalens, Tetraflex (KH3500; Lenstec, St. Petersburg, Florida, USA) and the 1CU (HumanOptics, Erlangen, Germany) all have Conformité Européene (CE) status, allowing their clinical use in Europe. These are the most commonly used AIOLs, although there is no worldwide data showing which is the

most implanted. The Tetraflex is currently undergoing Phase III FDA clinical trials. Further single-optic AIOLs including the Acuity C-Well (OrYehuda, Israel) and the AMO/Quest Vision (Santa Ana, California, USA) are at more developmental stages and very limited, if any, clinical data is available regarding these devices. CRYSTALENS

The Crystalens has seen six previous designs. The seventh iteration, the AT-45, was first implanted in 1998. In 2004, the AT-45 received FDA approval for correction of presbyopia in patients with cataract. The implant is a three-piece construction, comprising a single biconvex 4.5 mm optic, with two plate haptics each terminating in two polyamide loops to maintain fixation within the capsular bag. Adjacent to the optic are 50 per cent thickness grooved hinges in the plates. Plate-length is 10.5 mm and the diagonal loop-tip to loop-tip length is 11.5 mm.90 The square-edged optic is composed of Biosil, a biocompatible, third-generation silicone to maximise biocompatibility and flexibility, allowing comfortable passage of the lens through a three millimetre corneal incision. The AT-45 is designed to be posteriorly vaulted, resting on the capsular bag, near the nodal point of the eye, thus performing similarly to a more anteriorly-located 6.0 mm optic IOL. The enlarged 5.0 mm optic of the newer AT-50 (Figure 1) was intended to reduce potential problems with night-time vision and also addressed the concern of surgeons who may have been apprehensive in implanting an IOL with an optic of 4.5 mm.91 A further variation of the design is the Crystalens HD, with a 5.0 mm optic, modified to increase post-operative depth-of-field.92 The proposed mechanism of the Crystalens is based on the hydraulic suspension theory of accommodation.93 With accommodative effort, the ciliary muscle mass is redistributed and bulges into the vitreous cavity, causing the incompressible vitreous body to shift anteriorly and push the Crystalens optic forwards. In addition to a postero-anterior shift, flexing of the optic with ciliary muscle contraction,


444

resulting in steepening of the central zone may contribute significantly to the accommodative effect by increasing ocular aberrations, allowing for increased depth-of-field.92 The most comprehensive analysis of Crystalens performance is provided by the FDA multicentre clinical trial results.90 The phase 3 trial involved a 12-month follow-up of patients implanted either unilaterally or bilaterally with the AT-45. Combined visual acuities of 6/12 or better distance and J3 or better at near were measured in 78.8 per cent of patients who received monocular Crystalens and 96.7 per cent of patients implanted bilaterally. Seventy-three per cent of eyes had unaided near vision of 6/7.5 (J1) or for better, although with distance correction of refractive error to eliminate the pseudoaccommodative effects of myopia and astigmatism, this proportion reduced to 52 per cent. The small (4.5 mm) optic of the AT-45 was found not to result in reduced contrast sensitivity or increased glare symptoms, compared to a standard monofocal IOL. Several smaller studies have examined the objective performance of the AT-45 and measured the axial shift of the optic in response to pilocarpine95,96 or a near visual stimulus.97 Conflicting results were found following pilocarpine stimulation with one study reporting slight mean anterior movement of the optic,96 while another found a mean posterior shift.95 Marchini and associates97 used near-point induced accommodation and measured a mean anterior shift of the AT-45 optic of 0.33 ⫾ 0.25 mm, which alone would be insufficient to provide functional near acuity in distance-corrected eyes. Furthermore, accommodation measured objectively by retinoscopy (2.42 ⫾ 0.39 D) was smaller than the amplitude of accommodation perceived by the patient (5.79 D) by nearpoint determination, with the AT-45.98 TETRAFLEX

Designed by Robert Kellan, the Tetraflex (Figure 2) is a single-piece AIOL, made from hydrophilic hydroxyethylmethacrylate (HEMA), incorporating a 5.75 mm spherical optic with square edges to © 2010 The Authors



Figure 1. Crystalens AT-50 intraocular lens. The Crystalens AT-50 features a single 5.0 mm optic with two plate haptics, each terminating in two polyamide loops to maintain fixation.

Figure 3. Synchrony dual-optic intraocular lens. The one-piece Synchrony intraocular lens features a +32 D, 5.5 mm diameter anterior optic connected by spring-loaded articulations to a 6.0 mm, variable power posterior optic. The implant is designed to occupy the whole capsular bag, with aqueous filling the interoptic space.

Figure 2. Tetraflex single-optic intraocular lens (reprinted with permission from Lenstec Inc, St. Petersburg, Florida, USA). The Tetraflex features a 5.75 mm square-edged spherical optic. The closed loop haptics feature a five-degree anterior angulation to facilitate anterior movement with the whole capsular bag during accommodation.

reduce the incidence of posterior capsular opacification (PCO) by inhibiting migration of lens epithelial cells. The HEMA material is extremely flexible, with a 26

per cent water content, allowing capsular placement of the AIOL through a 2.5 mm corneal incision.99 The closed loop haptics feature a five degree anterior angulation,


Figure 4. Sarfarazi dual-optic elliptical intraocular lens. The Sarfarazi intraocular lens consists of two 5.0 mm diameter optics, connected by three haptics. Its elliptical shape is intended to conform to the natural morphology of the capsule.

which according to the manufacturer, facilitates forward movement of the implant with the whole capsular bag during accommodation.100 The Tetraflex is commercially available in Europe, China, Australia, Taiwan, Canada and the Middle East. The FDA clinical trial is ongoing and the manufacturer anticipates approval in late 2010. Limited clinical data are available on the Tetraflex, particularly regarding objective measures of biometric or refractive changes with accommodation. A study based in England analysed 59 patients implanted with the AIOL, 36 bilaterally.101 Six months post-operatively, 75.7 per cent of all subjects had at least 2.0 D of accommodation, measured subjectively both monocularly and binocularly by the push-up method and for the bilaterally implanted cohort, this proportion was greater, at 96 per cent. Uncorrected distance vision was also found to be good, with 92.2 per cent achieving 6/12 or better. An observational comparative study assessing the near visual ability of


445


patients implanted bilaterally with either Tetraflex or Crystalens (model AT-50 SE) found that functional reading performance was better in the Tetraflex group.99 A significantly higher proportion of Tetraflex patients achieved a reading speed of 80 words per minute (wpm) or more for print sizes smaller than 6/24. More recently, objective measures of ocular aberrations and Tetraflex optic movement during stimulus-driven accommodation, using AS-OCT, have been reported in a sample of 13 eyes of eight patients at least two years following implantation.35 While anterior movement of the lens optic was not observed (the lens actually moved backwards by 0.02 ⫾ 0.05 mm with accommodation), a variable change in ocular aberrations, particularly defocus, astigmatism, coma, trefoil and spherical aberration was observed with increased accommodative demand. The change in ocular aberrations due to lens flexure with accommodative effort appeared to be more beneficial to near function than the intended anterior shift of the IOL. 1CU

The most widely researched AIOL is the CE-certified HumanOptics AG Akkommodative 1CU, developed from the principles of Hanna, using finite element analysis.80 This single-piece AIOL incorporates a 5.5 mm biconvex optic and is made of a hydrophilic acrylic material. The 9.8 mm diameter implant features four wide-based haptics, which are thinner close to the optic to act as a hinge.60,102 The proposed mechanism of action of the 1CU is that the reduction in zonular tension following ciliary muscle contraction causes relaxation of the capsular bag, resulting in compression of the haptics and forward movement of the optic. Since becoming commercially available in Europe in 2001, several randomised controlled trials have compared the performance of the 1CU with standard nonaccommodating IOLs. Distance-corrected near vision (DCNV) was significantly better in the 1CU group than the control group in three of these studies,61,103,104 although two investigations failed to

detect any difference in DCNV between the implant groups.60,78 Over time, the accommodative ability of the 1CU may decrease and the enhanced near visual function provided by the implant has been found to be reduced at 12105 and 24 months.59 Those studies which have analysed axial optic movement in response to pilocarpine stimulation have found significantly more forward shift with the 1CU than the non-accommodative implants, although the maximum mean anterior movements reported for the AIOL are -0.82 ⫾ 0.3 mm in a randomised control trial61 and -0.83 ⫾ 0.25 mm in a non-randomised study.77 BIOCOMFOLD

A further early generation AIOL, the BioComFold, first became available in Europe in the late 1990s and two designs, the 43A and 43E were marketed. The BioComFold has a discontinuous circular configuration, with a central 5.8 mm anteriorly located optic connected to an outer ring by broad, perforated, angulated haptics. The implant is single-piece and composed of a hydrophilic acrylic material. The proposed mechanism of action of the BioComFold is that centripetal compression of the haptic ring with ciliary muscle contraction forces the optic further forwards.79 Designs 43A and 43E differ in overall diameter (9.8 mm versus 10.2 mm for 43A and 43E, respectively) and haptic angulation (10 ° versus 12 ° for 43A and 43E, respectively). Clinical data regarding the performance of the BioComFold are sparse, with no published studies having reported DCNV results following implantation. The movement of the optic in response to pilocarpine stimulation has been analysed by two groups. Legeais and co-workers106 reported a mean anterior shift of -0.71 ⫾ 0.55 mm one month post-operatively, while Findl and collaborators79 identified mean movements of just -0.222 ⫾ 0.24 mm for the 43E and -0.116 ⫾ 0.11 mm for the 43A three months after surgery. Despite the experimental evidence supporting the intended forward movement of optic-shift AIOLs, a major limitation of this design principle is that the potential


446

accommodative amplitude is limited by the implant power. Lower powered AIOLs for myopic eyes will provide less accommodation than higher-powered implants. Equation 1 illustrates that optic powers of 15 D, 20 D and 25 D will provide approximately 1.2 D, 1.5 D and 1.9 D of accommodation, respectively, with one millimetre of anterior shift. Given that the maximum pilocarpine-induced mean anterior lens movement reported in published studies is approximately 0.8 mm61,77 and maximum stimulus-driven movement is 0.33 mm97 the potential accommodative effect of optic-shift AIOLs appears to be limited. Flexing of the optic with ciliary muscle contraction may have an additional beneficial effect on near vision by increasing the power of the AIOL or by altering aberrations, which may serve to increase the eye’s depth of focus.35,94,107 The performance of optic-shift AIOLs may be further affected by natural postoperative capsular bag fibrosis and stiffening,6,47 which could restrict the intended axial movement. Extensive polishing to eradicate lens epithelial cells from the anterior capsule and thus reduce fibrosis and shrinkage has been trialled with the 1CU60 but was not found to enhance the accommodative ability of the implant compared to a control group.

Dual optic devices A key disadvantage of single-optic passiveshift IOLs is the influence of refractive error and hence optic power, on the resultant potential amplitude of accommodation. A dual optic AIOL design was first proposed by Hara, Yasuda and Yamada108 and consisted of two 8.0 mm diameter lenses connected by a coil spring, forming a rigid shell within the capsular bag. A modified design, with reduced diameter, 6.0 mm PMMA optics separated by four flexible loops was successfully implanted into living rabbit eyes.109 The Synchrony (Visiogen, Irvine, California, USA) and Sarfarazi110 dualoptic AIOLs have been developed more recently. The configuration of such AIOLs, with a high positively-powered and mobile anterior optic, connected to a stationary negatively-powered posterior © 2010 The Authors



optic, is designed to increase the potential accommodative amplitude. The anterior optic is more powerful than a single optic implant, thus its forward movement generates a greater dioptric power change. SYNCHRONY

The Synchrony IOL received CE approval in 2006 and Phase III US FDA clinical trials are ongoing. According to the manufacturer, more than 900 eyes have been implanted with Synchrony worldwide, 300 of these as part of the extended FDA trial.111 The design features a +32 D anterior optic connected by spring-loaded articulations to a larger posterior optic of variable negative power, depending on the refractive error of the patient. Measuring 9.8 mm horizontally and 9.5 mm vertically, the Synchrony IOL (Figure 3) is composed of silicone and may be injected through a 3.6 to 3.8 mm corneal incision. The anterior and posterior optics measure 5.5 mm and 6.0 mm, respectively. Like other dual-optic AIOLs, the implant is designed to occupy the whole capsular bag, with aqueous filling the interoptic space. At rest, during distance viewing, capsular tension causes relative compression of the optics and strain energy is stored in the interoptic articulations. With ciliary muscle contraction and relaxation of the zonules, capsular tension is reduced, causing release of the strain energy and forward displacement of the mobile anterior optic.112 The initial limited clinical data regarding Synchrony appear promising. Defocus curve analysis six months post-operatively demonstrated that 24 eyes implanted with Synchrony had a mean accommodative amplitude of 3.22 ⫾ 0.88 D compared to 1.65 ⫾ 0.58 D in a retrospective control group.113 Results from the ongoing trials involving longer periods and greater subject numbers are required before conclusions can be made regarding the efficacy of the Synchrony AIOL. SARFARAZI

Developed by FM Sarfarazi of Shenasa Medical LLC (Carlsbad, California, USA), the rights for development, marketing and production of the Sarfarazi dual-optic

elliptical IOL (Figure 4) were acquired by Bausch & Lomb (Rochester, New York, USA) in 2003. The implant comprises two 5.0 mm diameter optics connected by three haptics and the elliptical design conforms to the natural shape of the capsule.114 As with the Synchrony IOL, the Sarfarazi mechanism relies on forward movement of the anterior optic when tension on the capsule reduces with ciliary muscle contraction. In vivo implantation in rhesus monkey eyes has demonstrated that 7.0 to 9.0 D of pharmacologicallyinduced accommodation may be possible with the device,115 although there are no published studies reporting the performance of the Sarfarazi in human eyes. TURTLE

A further dual-optic IOL, based on the Alvarez lens principle,116 rather than optic shift, is in the early stages of development. The Turtle IOL117 inserted into the capsule, features a mechanical frame encasing two lenses that rotate in response to ciliary muscle contraction, causing a change in their combined optical power. In a porcine lens, 8.0 D of accommodation was achieved ex vivo using a lens stretcher designed to replicate the accommodative action of the ciliary muscle. The developers report that significant further modifications to the optical and mechanical design are necessary before human use is attempted. While potential accommodative amplitudes are significantly higher with dual optic compared to single optic designs, the issue of capsular elasticity remains a challenge. Prediction of the exact in vivo interoptic separation is important to achieve an emmetropic distance refraction, however, post-operative capsular shrinkage could affect this separation and also reduce the mobility of the anterior optic, limiting the accommodative ability of dual optic designs. Furthermore, because such devices are dependent on variations in capsular forces for their action, performance of yttrium aluminium garnet (YAG) laser capsulotomy in the event of posterior capsular opacification (PCO) could affect the accommodative ability of the IOL.


Considering lens designs in more widespread use, clinical studies suggest that rates of posterior capsular opacification are significantly higher in eyes implanted with single-optic AIOLs, compared with standard monofocal implants.90,118 Squareedged IOLs are well-known to inhibit the migration of lens epithelial cells that cause regeneration of the cortex.119 Hancox and colleagues118 observed that no patients in their cohort of 29 implanted with a monofocal IOL incorporating a 360 degree square-edge required YAG capsulotomy within two years of implantation, compared with 50 per cent of eyes implanted with the 1CU AIOL. The 1CU and Crystalens do not have square edges at the optichaptic junctions, allowing lens epithelial cells to spread into the retro-optic zones. The accommodative performance of single-optic AIOLs does not seem to be impeded following YAG capsulotomy,90,120 with some reports suggesting that the near performance of these implants may be enhanced by the treatment.60 The success of currently available AIOLs is difficult to gauge given the limited published data available in peer-reviewed journals. Methods employed to evaluate implanted AIOLs vary widely between studies, with several reporting only subjective acuity and accommodation. The testing charts, conditions and acuity notation are often not comparable in different studies and charts of the same type may not necessarily be identically reproduced.121 Of the studies that have measured optic movement objectively, the techniques used are varied (for example, PCI, IOLMaster, UBM) and most have relied on pharmacological stimulation of accommodation with pilocarpine, which causes powerful ciliary muscle contraction and does not reflect the natural accommodative response. Furthermore, there is a lack of longitudinal data. Reports of stability of AIOL performance at periods greater than 12 months post-operatively, such as that of Saiki and associates,122 are sparse. Schor, Bharadwaj and Burns123 simulated the stability of AIOLs, while Kuchle124 and Ossma and co-workers113 both limited the study to 12 months postoperatively. These studies also used a


447


diverse range of metrics to determine that AIOLs are stable over time with no significant difference between measures such as vision, distance and near visual acuity, accommodation, defocus curve fitting and lens position. Meanwhile, the near performance of currently available AIOLs has been reported to decrease over time,5,59,105 probably as a consequence of capsular fibrosis and shrinkage limiting optic movement.6,91 To verify the benefit of AIOLs in providing true accommodation, there is a critical need for more randomised, patient and practitioner-masked, clinical trials that involve long-term follow-up. In addition to subjective testing, objective evaluation of accommodative amplitude and optic movement, preferably without pharmacological agents, should be performed to distinguish between pseudoaccommodation and true accommodation.

Further AIOL design concepts

Figure 5. Diagram of the intended mechanism of the NuLens intraocular lens. To generate an increase in optical power from the distance vision state (A), a piston forces the flexible silicone gel through a round aperture in the PMMA plane, causing a bulging of the material (B). A steeper bulge generates greater accommodative power.

To provide higher amplitudes of accommodation and overcome some of the other shortcomings of existing AIOLs, a range of further design concepts is in the early stages of development. Magnetdriven active shift IOLs, initially proposed by Preussner and coauthors,125 are single optic devices combined with pairs of repulsing magnets to drive the lens implant-capsular bag system forwards during accommodation. As this concept is based on movement of the whole lenscapsule system rather than mobility of the optic within the capsule, such implants should be less susceptible to the effects of post-operative capsular fibrosis and posterior capsular opacification. Two inner magnets are implanted into the capsular bag with the IOLs and two pairs of outer magnets, polarised to repel the inner magnets, are positioned under the superior and inferior rectus muscle insertions. As the ciliary muscle contracts and the zonules relax, the capsule-IOL system is shifted anteriorly by magnetic repulsion. Magnet-driven active shift IOLs have been implanted in vivo into a small number of human eyes126 but no extended clinical trials have taken place. Optical systems that are able to change their surface curvature can provide high

levels of refractive power change with minimal axial displacement. Several AIOL designs based on this curvature change concept are known to be in development. The NuLens (Herzliya Pituach, Israel) AIOL consists of a fixed PMMA haptic system, secured to the ciliary sulcus with an anterior PMMA plane, a small chamber containing flexible silicone gel and a posterior piston operated by the empty, collapsed capsular bag. To generate a change in optical power, the piston pushes the flexible gel through a round hole in the PMMA plane, causing the silicone material to bulge (Figure 5), acting as a lens.127 A steeper bulge generates greater refractive power. In response to retinal blur, the ciliary muscle imparts force on the capsule and hence on the piston, to deform the silicone gel until a focused retinal image is formed.128 The NuLens design provides near focusing when the ciliary muscle is relaxed and disaccommodation under ciliary muscle contraction, which alone would necessitate an adaptation period. Additionally, the convergent eye movements that accompany accommodation


448

could prove problematic for this mechanism, as near vision would be associated with divergence and distance vision with maximal accommodation and convergence, leading to difficulties maintaining binocular single vision.7 It has been suggested by the NuLens developers that the brain could learn to uncouple accommodation and convergence with time,127 although patients could struggle functionally during the adaptation phase. The NuLens has been implanted in vivo in primate eyes127 and in human ARMD patients.128 After 12 months in human subjects, the implant was found to be stable and well-centred and to provide accommodative amplitudes (determined subjectively) of up to 10 D. The FluidVision (PowerVision Inc, Belmont, California, USA) AIOL is implanted into the capsular bag during cataract surgery and consists of hollow haptics and optic, allowing fluid displacement within the implant in response to ciliary muscle activity. During distance viewing, when the ciliary muscle is relaxed, relatively little force is imparted on the haptics by the equatorial region of the capsule, so that the haptics remain fluidfilled. With ciliary muscle contraction, the equatorial diameter of the capsule reduces as the zonules relax, resulting in an increase in pressure on the haptics and fluid displacement from the haptics to the optic. As the optic volume increases, its surface curvature steepens, resulting in increased dioptric power. Early clinical trials of the FluidVision IOL are underway, with initial results anticipated this year.129 A further curvature-change design is the SmartIOL (Medennium Inc, Irvine, California), which bears similarities to the capsular refilling concepts mentioned previously. It aims to overcome some of the problems associated with such techniques, including calculating precisely how much polymer to inject, controlling the postoperative refraction and removal of the lens mass through a micro-capsulorhexis. The SmartIOL is manufactured from a thermoplastic hydrophilic acrylic material to exact specifications regarding IOL power and anterior and posterior surface curvatures. The implant can be © 2010 The Authors



subsequently reconfigured due to its thermoplastic properties, at room temperature, into a 2 mm by 30 mm rod shape. During standard phacoemulsification surgery, the rod is inserted into the capsular bag, where it returns to its original shape in less than a minute, following exposure to body temperature.6,130 The gel-like implant fills the capsular bag and its mechanism is based on Helmholtz’s theory of accommodation, with predicted increases in axial thickness and surface curvatures and a reduction in equatorial diameter in response to the forces imparted by the capsule in response to ciliary muscle contraction.5,91 An additional advantage of this approach is that a full-sized implant may reduce capsular fibrosis, allowing good centration to be maintained and minimising edge glare. Unlike the gradient refractive index of the natural human lens, the SmartIOL has a uniform index. Therefore, to provide both emmetropia and a large amplitude of accommodation, the IOL must be of high refractive index or steeper in surface curvature than the natural lens. A lower index material, which may be used to correct myopic refractive errors would limit the potential accommodative ability.131 The SmartIOL has been implanted into human cadaver eyes but clinical trials have yet to begin.129 An additional strategy to provide a high amplitude of accommodation with an IOL has been developed by Alan Glazier in the United States, who proposed the use of fluids with differing refractive indices contained within the lens optic. The Liquilens (Vision Solutions Technologies, Rockville, Maryland) is dependent on gravity for its action and consists of two immiscible fluids that vary in refractive index. The majority of the optic (approximately 75 per cent) is filled with lower index fluid, with the higher index material floating on top during distance viewing. The motion of lowering the head during near tasks causes displacement of the higher index liquid downwards to coincide with the line of sight, providing a significant change in dioptric power. According to the inventor, up to 30 D of power change may be generated, proving

useful for low-vision patients,132 however, the lens does not provide true accommodation and behaves similarly to a bifocal lens in that intermediate vision is not restored and the effect is dependent on gaze position, meaning that complete spectacle independence may not be possible with this design. The Liquilens is currently undergoing preclinical testing with human studies planned in Europe to commence in the near future.12 CONCLUSIONS The newest AIOL design concepts undergoing development may provide enhanced performance compared to the early, passive-shift implants. The accommodative ability of passive-shift AIOLs is limited, with reported anterior movements insufficient to provide functionally significant amplitudes of accommodation.6,59,76,91,133 Even if the designs of such implants could be modified to enable the magnitude of forward movement to be increased, it is likely that the levels of anterior shift needed to provide accommodative amplitudes facilitating spectacle independence (for example, 2.0 mm) would interfere with anterior segment geometry, causing problems that include iris bulging and pigment dispersion.5,47 Despite the limited accommodative effects, passive-shift implants are used clinically around the world. It is essential that patients are carefully counselled prior to implantation to ensure realistic expectations of visual performance.89,134 Questionnaires asking about visual tasks and personality traits (for example, the Dell questionnaire)135 may be useful to identify patients likely to be dissatisfied with postoperative results despite clinically successful surgery. It is hoped that the newer AIOL designs such as dual optic devices, curvature change and active shift implants will provide greater accommodation. Although extraordinary potential amplitudes have been quoted by some developers, for example, 30 D for the Liquilens132 and 40 D for the NuLens,127 such levels of accommodation are unnecessary for the majority of patients. Given that nor-


mal presbyopic eyes may demonstrate approximately two dioptres of pseudoaccommodation54,136 and around 50 per cent of one’s accommodative amplitude may be used comfortably for a prolonged period,137 then for a habitual working distance of 35 cm, an AIOL capable of delivering four dioptres of true dynamic power change should allow spectacle independence at near. In addition to this higher amplitude than is possible with passive-shift IOLs, newer AIOL designs need to be capable of rapid disaccommodation to allow patients the visual function experienced before the onset of presbyopia. It is vital that long-term stability and efficacy can be demonstrated with newer accommodative implants. Implants that occupy the entire capsular bag, such as the SmartIOL, may deter such changes, ensuring long-term accommodative function. The issue of increased rates of posterior capsular opacification with AIOLs requires careful consideration, as YAG laser capsulotomy treatment could have a severely detrimental effect on the accommodative ability of implants that rely on changes in force applied by the capsule for their action, including the Synchrony lens. The accommodative performance of passive-shift implants does not seem to be adversely affected by YAG capsulotomy.90,120 Chemical treatment of the capsule during surgery, for example with cycloheximide and actinomycin, and careful removal of the entire lenticular contents to eradicate living lens epithelial cells can reduce the incidence of postoperative capsular opacification.48 To be used routinely in human subjects, toxic effects on neighbouring tissues would need to be avoided and sealed capsule irrigation has been suggested for safe application of pharmaceutical agents.138,139 In conclusion, numerous challenges need to be addressed successfully to restore accommodative function to the presbyopic eye. The ultimate goal of restoring eye focus to youthful levels is yet to be achieved and much further work is necessary before such a treatment becomes available for human use. Until such a time, the accommodating implants


449


currently available can provide some enhanced near function to presbyopic eyes and reduce spectacle dependence. REFERENCES 1. Vision 2020. The Cataract Challenge. Comm Eye Health 2000; 13: 17–19. 2. Sparrow JM. Cataract surgical rates: is there an overprovision in certain areas? Br J Ophthalmol 2007; 91: 852–853. 3. Apple DJ, Peng Q, Ram J. The 50th anniversary of the intraocular lens and a quiet revolution. Ophthalmology 1999; 106: 1861–1862. 4. Olsen T. Improved accuracy of intraocular lens power calculation with the Zeiss IOL master. Acta Ophthalmol Scand 2007; 85: 84–87. 5. Menapace R, Findl O, Kreichbaum K, LeydoltKoeppl C. Accommodating intraocular lenses: a critical review of present and future concepts. Graefes Arch Clin Exp Ophthalmol 2007; 245: 473– 489. 6. Glasser A. Restoration of accommodation: surgical options for correction of presbyopia. Clin Exp Optom 2008; 91: 279–295. 7. Schor CM, Charles F. Prentice Award Lecture 2008: Surgical correction of presbyopia with intraocular lenses designed to accommodate. Optom Vis Sci 2009; 86: 1028–1041. 8. Millodot M. Dictionary of Optometry and Visual Science, 6th ed. Oxford, UK: Butterworth Heinemann, 2008. 9. Helmhotz H. Uber die akkommodation des auges. Arch Ophthalmol 1855; 1: 1–74. 10. Gilmartin B. The aetiology of presbyopia: a summary of the role of lenticular and extralenticular structures. Ophthalmic Physiol Opt 1995; 15: 431–437. 11. Strenk SA, Semmlow JL, Strenk LM, Munoz P, Gronlund-Jacob J, De Marco JK. Age-related changes in human ciliary muscle and lens: a magnetic resonance imaging study. Invest Ophthalmol Vis Sci 1999; 40: 1162–1169. 12. Charman WN. The eye in focus: accommodation and presbyopia. Clin Exp Optom 2008; 91: 207– 225. 13. Croft MA, Glasser A, Kaufman PL. Accommodation and presbyopia. Int Ophthalmol Clin 2001; 41: 33–46. 14. Koretz JF, Kaufman PL, Neider MW, Goeckner PA. Accommodation and presbyopia in the human eye: aging of the anterior segment. Vision Res 1989; 29: 1685–1692. 15. Atchison DA, Markwell EL, Kasthurirangan S, Pope JM, Smith G, Swann PG. Age-related changes in optical and biometric characteristics of emmetropic eyes. J Vis 2008; 8: 1–20. 16. Koretz JF, Handleman GH. Modeling age-related loss in the human eye. Math Mod 1986; 7: 1003– 1014. 17. Sakabe I, Oshika T, Lim SJ, Apple DJ. Anterior shift of zonular insertion into the anterior surface of human crystalline lens with age. Ophthalmology 1998; 105: 295–299. 18. Atchison DA. Accommodation and presbyopia. Ophthalmic Physiol Opt 1995; 15: 255–272. 19. Glasser A, Campbell MCW. Biometric, optical and physical changes in the isolated human crystalline lens in relation to presbyopia. Vision Res 1999; 39: 1991–2015.


450

20. Fisher RF, Pettet BE. Presbyopia and the water content of the human crystalline lens. J Physiol 1973; 234: 443–447. 21. Fisher RF. Elastic constants of the human lens capsule. J Physiol 1969; 201: 1–19. 22. Charman WN. Restoring accommodation to the presbyopic eye: how do we measure success? J Cataract Refract Surg 2003; 29: 2251–2254. 23. Pardue MT, Sivak JG. Age-related changes in human ciliary muscle. Optom Vis Sci 2000; 77: 204–210. 24. Bacskulin A, Gast R, Bergmann U, Guthoff R. Ultrasound biomicroscopy imaging of accommodative configuration changes in the presbyopic ciliary body. Ophthalmologe 1996; 93: 199–203. 25. Stachs O, Martin H, Kirchhoff A, Stave J, Terwee T, Guthoff R. Monitoring accommodative ciliary muscle function using three-dimensional ultrasound. Graefes Arch Clin Exp Ophthalmol 2002; 240: 906–912. 26. Strenk SA, Strenk LM, Guo S. Magnetic resonance imaging of aging, accommodating, phakic, and pseudophakic ciliary muscle diameters. J Cataract Refract Surg 2006; 32: 1792–1798. 27. Niessen AGJE, de Jong LB, van der Heijde GL. Pseudoaccommodation in pseudophakia. Eur J Implant Refract Surg 1992; 4: 91–94. 28. Langenbucher A, Seitz B, Huber S, Nguyen NX, Kuchle M. Theoretical and measured pseudophakic accommodation after implantation of a new accommodative posterior chamber intraocular lens. Arch Ophthalmol 2003; 121: 1722–1727. 29. Betman JW. Apparent accommodation in aphakic eyes. Am J Ophthalmol 1950; 33: 921–928. 30. Hayashi K, Hayashi H, Nakoa F, Hayashi F. Aging changes in apparent accommodation in eyes with a monofocal intraocular lens. Am J Ophthalmol 2003; 135: 432–436. 31. Nakazawa M, Ohtsuki K. Apparent accommodation in pseudophakic eyes after implantation of posterior chamber intraocular lenses. Am J Ophthalmol 1983; 96: 435–438. 32. Elder MJ, Murphy C, Sanderson GF. Apparent accommodation and depth of field in pseudophakia. J Cataract Refract Surg 1996; 22: 615–619. 33. Huber C. Myopic astigmatism as a substitute for accommodation in pseudophakia. Dev Ophthalmol 1981; 5: 17–26. 34. Vezella F, Calossi A. Mulitifocal effect of againstthe-rule myopic astigmatism in pseudophakic eyes. Refract Corneal Surg 1993; 9: 58–61. 35. Wolffsohn JS, Davies LN, Gupta N, Naroo SA, Gibson GA, Mihashi T, Shah S. Investigating the mechanism of action of the Tetraflex KH3500 accommodative intraocular lens. J Refract Surg 2010; 26: [Epub ahead of print] doi.10.3928/ 1081597X-20100114-04. 36. Sippel KC, Jain S, Azar DT. Monovision achieved with Excimer laser refractive surgery. Int Ophthalmol Clin 2001; 41: 91–101. 37. Reilly CD, Lee WB, Alvarenga L, Caspar J, GarciaFerrer F, Mannis MJ. Surgical monovision and monovision reversal in LASIK. Cornea 2006; 25: 136–138. 38. Vinciguerra P, Nizzola GM, Nizzola F, Ascari A, Azzolini M, Epstein D. Zonal refractive keratectomy for presbyopia. J Refract Surg 1998; 14: S218S221. 39. Bauerberg JM. Centred vs. inferior off-centre ablation to correct hyperopia and presbyopia. J Refract Surg 1999; 15: 66–69.

40. Yilmaz OF, Bayraktar S, Agca A, Yilmaz B, McDonald MB, van de Pol C. Intracorneal inlay for the surgical correction of presbyopia. J Cataract Refract Surg 2008; 34: 1921–1927. 41. Leyland M, Zinicola E. Multifocal versus monofocal intraocular lenses in cataract surgery: a systematic review. Ophthalmology 2003; 110: 1789– 1798. 42. Percival SP, Setty SS. Prospectively randomized trial comparing the pseudoaccommodation of the AMO ARRAY multifocal lens and a monofocal lens. J Cataract Refract Surg 1993; 19: 26–31. 43. Rossetti L, Carraro F, Rovati M, Orzalesi N. Performance of diffractive multifocal intraocular lenses in extracapsular cataract surgery. J Cataract Refract Surg 1994; 20: 124–128. 44. Kamlesh, Dadeya S, Kaushik S. Contrast sensitivity and depth of focus with aspheric multifocal versus conventional monofocal intraocular lens. Can J Ophthalmol 2001; 36: 197–201. 45. Javitt JC, Steinert RF. Cataract extraction with multifocal intraocular lens implantation: a multinational clinical trial evaluating clinical, functional and quality-of-life outcomes. Ophthalmology 2000; 107: 2040–2048. 46. Allen ED, Burton RL, Webber SK, Haaskjold E, Sandvig K, Jyrkkïo H, Leite E et al. Comparison of a diffractive bifocal and a monofocal intraocular lens. J Cataract Refract Surg 1996; 22: 446–451. 47. Dick HB. Accommodative intraocular lenses: current status. Curr Opin Ophthalmol 2005; 16: 8–26. 48. Koopmans SA, Terwee T, Glasser A, Wendt M, Vilipuru AS, van Kooten TG, Norrby S et al. Accommodative lens refilling in rhesus monkeys. Invest Ophthalmol Vis Sci 2006; 47: 2976–2984. 49. Nishi O, Nishi K. Accommodation amplitude after lens refilling with injectable silicone by sealing the capsule with a plug in primates. Arch Ophthalmol 1998; 116: 1358–1361. 50. Nishi O, Nakai Y, Yamada Y, Mizumoto Y. Amplitudes of accommodation of primate lenses refilled with two types of inflatable endocapsular balloons. Arch Ophthalmol 1993; 111: 1677–1684. 51. Nishi Y, Mireskandari K, Khaw P, Findl O. Lens refilling to restore accommodation. J Cataract Refract Surg 2009; 35: 374–382. 52. Barclay L. Accommodating intraocular lenses allow near and far vision: a newsmaker interview with J. Stewart Cumming. Medscape Medical News 2003 [cited 11 January 2010] Available online at http://www.medscape.com/viewarticle/465867. 53. Rosenfield M, Cohen AS. Repeatability of clinical measurements of the amplitude of accommodation. Ophthalmic Physiol Opt 1996; 16: 247–249. 54. Ostrin LA, Glasser A. Accommodation measurements in a prepresbyopic and presbyopic population. J Cataract Refract Surg 2004; 30: 1435–1444. 55. Mathews S. Scleral expansion surgery does not restore accommodation in human presbyopia. Ophthalmology 1999; 106: 873–877. 56. Langenbucher A, Huber S, Nguyen NX, Seitz B, Gusek-Schneider GC, Kuchle M. Measurement of accommodation after implantation of an accommodating posterior chamber intraocular lens. J Cataract Refract Surg 2003; 29: 677–685. 57. Kuchle M, Seitz B, Langenbucher A, GusekSchneider GC, Martus P, Nguyen NX. Comparison of 6-month results of implantation of the 1CU accommodative intraocular lens with conventional intraocular lenses. Ophthalmology 2004; 111: 318–324.



58. Dick HB, Kaiser S. Dynamic aberrometry during accommodation of phakic eyes and eyes with potentially accommodative intraocular lenses [German]. Ophthalmologe 2002; 99: 825–877. 59. Wolffsohn JS, Hunt OA, Naroo S, Gilmartin B, Shah S, Cunliffe IA, Benson MT et al. Objective accommodative amplitude and dynamics with the 1-CU accommodative intraocular lens. Invest Ophthalmol Vis Sci 2006; 47: 1230–1235. 60. Findl O, Kriechbaum K, Menapace R, Koeppl C, Sacu S, Wirtitsch M, Buehl W et al. Laser interferometric assessment of pilocarpine-induced movement of an accommodating intraocular lens: a randomized trial. Ophthalmology 2004; 111: 1515–1521. 61. Sauder G, Degenring RF, Kamppeter B, Hugger P. Potential of the 1 CU accommodative intraocular lens. Br J Ophthalmol 2005; 89: 1289–1292. 62. Prabakaran S, Dirani M, Chia A, Gazzard G, Fan Q, Leo SW, Ling Y et al. Cycloplegic refraction in preschool children: comparisons between the hand-held autorefractor, table-mounted autorefractor and retinoscopy. Ophthalmic Physiol Opt 2009; 29: 422–426. 63. Jorge J, Queiros A, Gonzalez-Meijome J, Fernandes P, Almeida JB, Parafita MA. The influence of cycloplegia in objective refraction. Ophthalmic Physiol Opt 2005; 25: 340–345. 64. Whitefoot H, Charman WN. Dynamic retinoscopy and accommodation. Ophthalmic Physiol Opt 1992; 12: 8–17. 65. Rutstein RP, Fuhr PD, Swiatocha J. Comparing the amplitude of accommodation determined objectively and subjectively. Optom Vis Sci 1993; 70: 496–500. 66. Hunt OA, Wolffsohn JS, Gilmartin B. Evaluation of the measurement of refractive error by the PowerRefractor: a remote, continuous and binocular measurement system of oculomotor function. Br J Ophthalmol 2003; 87: 1504–1508. 67. Blade PJ, Candy TR. Validation of the PowerRefractor for measuring human infant refraction. Optom Vis Sci 2006; 83: 346–353. 68. Sheppard AL, Davies LN. Clinical Evaluation of the Grand Seiko Auto Ref/ Keratometer WAM-5500. Ophthalmic Physiol Opt 2010; 30: 143– 151. 69. Mallen EAH, Wolffsohn JSW, Gilmartin B, Tsujimura S. Clinical evaluation of the ShinNippon SRW-5000 autorefractor in adults. Ophthalmic Physiol Opt 2001; 21: 101–107. 70. McBrien N, Millodot M. Clinical evaluation of the Canon Autoref R-1. Am J Optom Physiol Opt 1985; 62: 786–792. 71. Davies LN, Mallen EA, Wolffsohn JS, Gilmartin B. Clinical evaluation of the Shin-Nippon NVision-K 5001/Grand Seiko WR-5100 K autorefractor. Optom Vis Sci 2003; 80: 320–324. 72. Thibos LN. Principles of Hartmann-Shack aberrometry. J Refract Surg 2000; 16: S563-S565. 73. Platt BC, Shack R. History and principles of Shack-Hartmann wavefront sensing. J Refract Surg 2001; 17: S573-S577. 74. Rodriguez P, Navarro R, Gonzalez L, Hernandez JL. Accuracy and reproducibilty of Zywave, Tracey, and experimental aberrometers. J Refract Surg 2004; 20: 810–817. 75. Mirshahi A, Buhren J, Gerhardt D, Kohnen T. In vivo and in vitro repeatability of Hartmann-Shack aberrometry. J Cataract Refract Surg 2003; 29: 2295–3001.

76. Findl O, Leydolt C. Meta-analysis of accommodating intraocular lenses. J Cataract Refract Surg 2007; 33: 522–527. 77. Auffarth GU, Martin M, Fuchs HA, Rabsilber TM, Becker KA, Schmack I. Validity of anterior chamber depth measurements for the evaluation of accommodation after implantation of an accommodative Humanoptics 1CU intraocular lens [German]. Ophthalmologe 2002; 99: 815–819. 78. Hancox J, Spalton DJ, Heatley G, Jayaram H, Marshall J. Objective measurement of intraocular lens movement and dioptric change with a focus shift accommodating intraocular lens. J Cataract Refract Surg 2006; 32: 1098–1003. 79. Findl O, Kiss B, Petternel V, Menapace R, Georgopoulos M, Rainer G, Drexler W. Intraocular lens movement caused by ciliary muscle contraction. J Cataract Refract Surg 2003; 29: 669–676. 80. Kuchle M, Nguyen NX, Langenbucher A, Gusek-Schneider GC, Seitz B, Hanna KD. Implantation of a new accommodative posterior chamber intraocular lens. J Refract Surg 2002; 18: 208–216. 81. Davies LN, Gibson GA, Sheppard AL, Wolffsohn JS. In vivo biometric evaluation of phakic and pseudophakic eyes during accommodation with optical coherence tomography. Invest Ophthalmol Vis Sci 2008; 49: E-Abstract 3777. 82. Holzer MP, Mamusa M, Auffarth GU. Accuracy of a new partial coherence interferometry analyzer for biometric measurements. Br J Ophthalmol 2009; 93: 807–810. 83. Buckhurst PJ, Wolffsohn JS, Shah S, Naroo SA, Davies LN, Berrow EJ. A new optical low coherence reflectometry device for ocular biometry in cataract patients. Br J Ophthalmol 2009; 93: 949– 953. 84. McLeod SD, Portney V, Ting A. A dual optic accommodating foldable intraocular lens. Br J Ophthalmol 2003; 87:1083–1085. 85. Kriechbaum K, Findl O, Koeppl C, Menapace R, Drexler W. Stimulus-driven versus pilocarpineinduced biometric changes in pseudophakic eyes. Ophthalmology 2005; 112: 453–459. 86. Glasser A. Restoration of accommodation. Curr Opin Ophthalmol 2006; 17: 12–18. 87. Uthoff D, Holland D, Hepper D, Gulati A, Koch L, Haigis W. Laser interferometric measurements of accommodative changes in the position of an optic-shift intraocular lens. J Refract Surg 2009; 25: 416–420. 88. Koeppl C, Findl O, Kriechbaum K, Drexler W. Comparison of pilocarpine-induced and stimulus-driven accommodation in phakic eyes. Exp Eye Res 2005; 80: 795–800. 89. Buznego C, Trattler WB. Presbyopia-correcting intraocular lenses. Curr Opin Ophthalmol 2009; 20: 13–18. 90. Cumming JS, Colvard DM, Dell SJ, Doane J, Fine IH, Hoffman RS, Packer M et al. Clinical evaluation of the Crystalens AT-45 accommodating intraocular lens: results of the US Food and Drug Administration clinical trial. J Cataract Refract Surg 2006; 32: 812–825. 91. Doane JF, Jackson RT. Accommodative intraocular lenses: considerations on use, function and design. Curr Opin Ophthalmol 2007; 18: 318–324. 92. Pepose JS. Design strategies for new accommodating IOLs. Cataract Refract Surg Today 2009; 9: 39–45.


93. Coleman DJ. On the hydraulic suspension theory of accommodation. Trans Am Ophthalmol Soc 1986; 84: 846–868. 94. Cumming JS. Performance of the crystalens. Author reply. J Refract Surg 2006; 22: 633– 634. 95. Koeppl C, Findl O, Menapace R, Kriechbaum K, Wirtitsch M, Buehl W, Sacu S et al. Pilocarpineinduced shift of an accommodating intraocular lens: AT-45 Crystalens. J Cataract Refract Surg 2005; 31: 1290–1297. 96. Stachs O, Schneider H, Beck R, Guthoff R. Pharmacological-induced haptic changes and the accommodative performance in patients with the AT-45 accommodative IOL. J Refract Surg 2006; 22: 145–150. 97. Marchini G, Pedrotti E, Sartori P, Tosi R. Ultrasound biomicroscopic changes during accommodation in eyes with accommodating intraocular lenses. J Cataract Refract Surg 2004; 30: 2476– 2482. 98. Macsai MS, Padnick-Silver L, Fontes BM. Visual outcomes after accommodating intraocular lens implantation. J Cataract Refract Surg 2006; 32: 628–633. 99. Brown D, Dougherty P, Gills JP, Hunkeler J, Sanders DR, Sanders ML. Functional reading acuity and performance: comparison of 2 accommodating intraocular lenses. J Cataract Refract Surg 2009; 35: 1711–1714. 100. Lenstec. How the Tetraflex is designed to use the natural accommodation process 2009 [cited 10 March 2010] Available online at: http://www. lenstec.com/lenstec/tf_accom_process.html. 101. Sanders DR, Sanders ML. Visual performance results after Tetraflex accommodating intraocular lens implantation. Ophthalmology 2007; 114: 1679–1684. 102. Kuchle M, Seitz B, Langenbucher A, Martus P, Nguyen NX. Stability of refraction, accommodation and lens position after implantation of the 1CU accommodating posterior chamber intraocular lens. J Cataract Refract Surg 2003; 29: 2324–2329. 103. Mastropasqua L, Toto L, Nubile M. Clinical study of the 1CU accommodating intraocular lens. J Cataract Refract Surg 2003; 29: 1307–1312. 104. Heatley CJ, Spalton DJ, Hancox J. Fellow eye comparison between the 1CU accommodative intraocular lens and the Acrysof MA30 monofocal intraocular lens. Am J Ophthalmol 2005; 140: 207–213. 105. Dogru M, Honda R, Omoto M, Toda I, Fujishima H, Arai H, Matsuytama M et al. Early visual results with the 1CU accommodating intraocular lens. J Cataract Refract Surg 2005; 31: 895–902. 106. Legeais J-M, Werner L, Werner L, Abenhaim A, Renard G. Pseudoaccommodation: BioComFold versus a foldable silicone intraocular lens. J Cataract Refract Surg 1999; 25: 262–267. 107. Dick HB. Single optic accommodative intraocular lenses. Ophthalmol Clin North Am 2006; 19: 107–124. 108. Hara T, Yasuda A, Yamada Y. Accommodative intraocular lens with spring action. Part 1. Design and placement in an excised animal eye. Ophthalmic Surg 1990; 21: 128–133. 109. Hara T, Yasuda A, Mizumoto Y, Yamada Y. Accommodative intraocular lens with spring action. Part 2: Fixation in the living rabbit. Ophthalmic Surg 1992; 23: 632–635.


451


110. Sarfarazi FM. Sarfarazi dual optic accommodating intraocular lens. Ophthalmol Clin North Am 2006; 19: 125–128. 111. Visiogen. Visiogen achieves full enrolment of Synchrony subjects in its Phase III clinical trial. 2007 [cited 1 March 2010] Available online at: http://www.visiogen.com/pressreleases/Phase %20III%release.pdf. 112. McLeod SD, Vargas LG, Portney V, Ting A. Synchrony dual-optic accommodating intraocular lens. Part 1: Optical and biomechanical principles and design considerations. J Cataract Refract Surg 2007; 33: 37–46. 113. Ossma I, Galvis A, Vargas LG, Trager M, Vagefi M, McLeod SD. Synchrony dual-optic accommodating intraocular lens. Part 2: Pilot clinical evaluation. J Cataract Refract Surg 2007; 33: 47–52. 114. Sarfarazi FM. Sarfarazi elliptical accommodative intraocular lens for small incision surgery. United States Patent Application 10201615 (2002) [cited 10 March 2010]. Available online at http://www. google.co.uk/patents?q=sarfarazi+lens. 115. McDonald JP, Croft MA, Vinje E, Glasser A, Heatley GA, Kaufman PL, Sarfarazi FM. Sarfarazi elliptical accommodating intraocular lens in rhesus monkey eyes in vitro and in vivo. Invest Ophthalmol Vis Sci 2003; 44: E-Abstract 256. 116. Barton IM, Dixit SM, Summers LJ, Avicola K, Wilhelmsen J. Diffractive Alvarez lens. Optics Letters 2000; 25: 1–3. 117. Hermans EA, Terwee TT, Koopmans SA, Dubbelman M, van der Heijde RGL, Heethar RM. Development of a ciliary muscle-driven accommodating intraocular lens. J Cataract Refract Surg 2008; 34: 2133–2138. 118. Hancox J, Spalton DJ, Heatley CJ, Jayaram H, Yip J, Boyce J, Marshall J. Fellow-eye comparison of posterior capsular opacification rates after implantation of 1CU accommodating and AcrySof MA30 monofocal intraocular lenses. J Cataract Refract Surg 2007; 33: 413–417. 119. Dewey S. Posterior capsule opacification. Curr Opin Ophthalmol 2006; 17: 45–53. 120. Nguyen NX, Seitz B, Reese S, Langenbucher A, Kuchle M. Accommodation after Nd: YAG capsulotomy in patients with accommodative posterior chamber lens 1CU. Graefes Arch Clin Exp Ophthalmol 2005; 243: 120–126. 121. Gupta N, Wolffsohn JS, Naroo SA. Comparison of near visual acuity and reading metrics in presbyopia correction. J Cataract Refract Surg 2009; 35: 1401–1409. 122. Saiki M, Negishi K, Dogru M, Yamaguchi T, Tsubota K. Biconvex posterior chamber accommodating intraocular lens implantation after cataract surgery: long-term outcomes. J Cataract Refract Surg 2010; 36: 603–608. 123. Schor CM, Bharadwaj SR, Burns CD. Dynamic performance of accommodating intraocular lenses in a negative feedback control system: a simulation-based study. Comput Biol Med 2007; 37: 1020–1035. 124. Küchle M. Stability of refraction, accommodation, and lens position after implantation of the 1CU accommodating posterior chamber intraocular lens. J Cataract Refract Surg 2009; 29: 2324– 2329. 125. Preussner P-R, Wahl J, Gerl R, Kreiner C, Serester A. Accommodative lens implant. Ophthalmologe 2001; 98: 97–102.

126. Menapace R. Pre-loaded shift IOL systems: Concepts and first clinical experiences [German]. Proceedings of the 19th annual meeting of the DGII; 2005; Feb 18–19. Magdeburg, Germany. 127. Ben-Nun J, Alió JL. Feasibility and development of a high-power real accommodating intraocular lens. J Cataract Refract Surg 2005; 31: 1802–1808. 128. Alió JL, Ben-nun J, Rodriguez-Prats JL, Plaza AB. Visual and accommodative outcomes 1 year after implantation of an accommodating intraocular lens based on a new concept. J Cataract Refract Surg 2009; 35: 1671–1678. 129. Alfonso JF, Carones F, Cionni RJ, Claoue C, Cochener B, Goes FJ, Pepose JS et al. Accommodating and light-adjustable technologies. Cataract Refract Surg Today Eur 2010 January: 47–48 [cited 17 March 2010]. Available online at: http://www. bmctoday.net/crstodayeurope/pdfs/euro0110_ accommodating.pdf. 130. Stephenson M. What’s next in accommodative IOLs? Rev Ophthalmol 2006; 13 [cited 10 March 2010] Available online at http://www.revophth. com/index.asp?page=1_874.htm. 131. Ho A, Erickson P, Manns F, Pham DT, Parel J-M. Theoretical analysis of accommodation amplitude and ametropia correction by varying refractive index in Phaco-Ersatz. Optom Vis Sci 2001; 78: 405–410. 132. Bethke W. A sneak peek into the IOL pipeline. Rev Ophthalmol. 2007; 14 [cited 17 March 2010] Available online at http://www.revophth.com/ index.asp?page=1_13613.htm. 133. Comander J, Pineda R. Accommodating intraocular lenses: theory and practice. Int Ophthalmol Clin 2010; 50: 107–117. 134. Pepose JS. Maximising satisfaction with presbyopia-correcting intraocular lenses: the missing links. Am J Ophthalmol 2008; 146: 641–648. 135. Dell SJ. Cataract and refractive lens exchange questionnaire. 2010: [cited 10 January 2010] Available online at http://www.crstoday.com/ Pages/patientQ.php. 136. Duane A. Normal values of the accommodation at all ages. J Am Med Assoc 1912; 59: 1010. 137. Millodot M, Millodot S. Presbyopia correction and the accommodation in reserve. Ophthalmic Physiol Opt 1989; 9: 126–132. 138. Maloof A, Neilson G, Milverton EJ, Pandey SK. Selective and specific targeting of lens epithelial cells during cataract surgery using sealed-capsule irrigation. J Cataract Refract Surg 2003; 29: 1566– 1568. 139. Maloof A, Pandey SK, Neilson G, Milverton EJ. Selective death of lens epithelial cells using demineralized water and Trition X-100 with PerfectCapsule sealed capsule irrigation; a histological study in rabbit eyes. Arch Ophthalmol 2005; 123: 1378–1384.

Corresponding author: Dr Leon N. Davies Ophthalmic Research Group School of Life and Health Sciences Aston University Birmingham B4 7ET UNITED KINGDOM E-mail: [email protected]


452
