Multifocal intraocular lenses and retinal diseases

Purpose Multifocal intraocular lenses (MIOLs) are often discouraged in patients with or at risk of retinal disorders (including diabetic retinopathy, age-related macular degeneration, and epiretinal membranes), as MIOLs are believed to reduce contrast sensitivity (CS). Concerns with MIOLs have also been raised in individuals with visual field defects, fixation instability or eccentric preferred retinal locations. The aim of this study is to review the influence of MIOL on quality of vision in patients with retinal diseases. Methods We reviewed the PubMed and Web of Science databases to identify relevant studies using the following keywords: multifocal intraocular lens, cataract surgery, cataract extraction, lens exchange, diabetic retinopathy, age-related macular degeneration, and contrast sensitivity. Results Studies evaluating CS in MIOLs present conflicting results: MIOLs either did not influence CS or resulted in worse performance under low-illuminance conditions and higher spatial frequencies when compared to monofocal IOLs. Nevertheless, MIOLs preserved CS levels within the age-matched normal range. Two studies reported that patients with concurrent retinal diseases receiving a MIOL, both unilaterally and bilaterally, reported a significant improvement in visual-related outcomes. Individuals with a monofocal IOL in one eye and a MIOL in the fellow eye reported greater subjective satisfaction with the MIOL. Conclusion We were unable to find evidence suggesting that patients with retinal diseases should be advised against MIOLs. Nevertheless, more research is needed to address the aforementioned concerns and to optimize the use of MIOLs in eyes with retinal disease. Electronic supplementary material The online version of this article (10.1007/s00417-020-04603-0) contains supplementary material, which is available to authorized users.


Introduction
Advances in cataract surgery and refractive lens exchange have enabled these techniques to be used to achieve precise and desired refractive outcomes [1]. This has raised patients' expectations of excellent uncorrected distance visual acuity [2]. However, with monofocal intraocular lenses (IOLs), the desire for freedom from spectacles cannot be completely met. Multifocal intraocular lenses (MIOLs) are used more commonly and to a considerable extent for refractive purposes in non-cataractous eyes [3]. It is believed that as MIOLs decrease contrast sensitivity, so they are advised against in patients with retinal disorders.
MIOLs utilize diffractive or refractive optics in order to produce two or more foci. A diffractive MIOL generates multifocality based on light interference. It incorporates a pattern consisting of a series of annular concentric grooves less than 1 micron in depth, which are engraved around the optical axis on either the front or the back surface of a lens (the echelette technology). With the refractive design, multifocality is achieved with light refraction on the MIOL surfaces based on Snell's law.
The performance of refractive design MIOLs depends on pupil size and MIOL centration.
The increasing popularity of MIOLs underlines the importance of reviewing scientific evidence regarding their suitability in patients with ocular comorbidities to aid preoperative assessment and proper patient selection in MIOL candidates. The aim of this study is to review the influence of MIOL on quality of vision in patients with retinal diseases.

Materials and methods
The PubMed and Web of Science databases were the main resources used to investigate the medical literature. An extensive search was performed to identify relevant articles concerning "multifocal intraocular lenses" and "retinal diseases" up to June 30, 2018 (Appendix 1). The following keywords were used in various combinations: multifocal intraocular lens, cataract surgery, cataract extraction, lens exchange, diabetic retinopathy, age-related macular degeneration, and contrast sensitivity. The search identified 247 unique articles. Of the studies retrieved by this method, we reviewed all publications in English and abstracts of non-English publications. The reference lists of the articles analyzed were also considered as a potential source of information. We attempted to present all publications that employed MIOLs for patients with retinal diseases. Studies were critically reviewed to create an overview and guidance for further research. No attempts were made to discover unpublished data. In addition to the PubMed and Web of Science searches, selected chapters from relevant textbooks were included.

Contrast sensitivity (CS) and age
Various procedures and systems are employed to evaluate contrast sensitivity. The results of these evaluations be affected by differences in methodology, including light conditions, speed of performing the test, or decision-making criteria. In 1978, Arden and Jacobson claimed that contrast sensitivity is independent of age, and since then, several studies have sought an association between contrast sensitivity and age [4]. Studies analyzing the relationship between CS and age are presented in Table 1. It might be concluded that contrast sensitivity decreases with age and that the greatest decrease is observed at higher spatial frequencies. Age and cataract are independently associated with this decline, and posterior subcapsular cataract affects CS in the highest degree. Lower CS was also reported in females and in Chinese, when compared to other races present in Singapore [5,6]. Moreover, CS at higher spatial frequencies is lower in myopes compared to emmetropes [5].
Burton et al. [12] suggested that optical rather than neural changes in the visual system contribute to loss of spatial contrast sensitivity at a photopic level in the elderly. This small loss in CS was presumably due to interaction of a laser speckle effect and increased light scattering in the aged eye. On the other hand, Elliot et al. [27] reported that the decrease in contrast sensitivity is due to neural loss. In their study, senile miosis and reduced optical transmission, which are believed to influence CS, were mimicked in younger subjects by reducing retinal illumination and did not result in a decrease in CS. Higgins et al. [17] believe that the high-spatial frequency decline in CS, although it is comparatively small, is too large to be due to changes in lens density related to age. This was confirmed by Owsley et al. [23], who demonstrated that after cataract surgery, elderly patients still have decreased CS at higher frequencies, although they have a crystalline IOL. The decline in visual performance might also be due to spatial integration and difficulty in processing visual information in the presence of noise [28]. Morrison and Jay [29] confirmed with laser interferometry that the optical functions with aging remain unchanged, while neural function significantly declines.

CS and MIOLs
Studies analyzing CS in MIOLs present conflicting results, as seen in Table 2. Comparing CS outcomes is difficult due to the differences in the tests used and different illumination levels and inconsistencies in the variables reported. One might conclude that CS with MIOLs was lower than with monofocal IOLs in at least some conditions; in some studies, MIOLs performed worse under low-illuminance conditions and at higher spatial frequencies. The outcome regarding CS might depend on the MIOL model and design: diffractive optics influence CS to a lesser degree [30]. However, the quality of evidence is poor. Furthermore, none of the studies presented an association between CS and the quality of vision [31]. CS improved with time and achieved an age normal range of 3-12 months after surgery. Similar results were presented in the meta-analysis by Rosen et al. [32] and in the review by Wang et al. [33]. Thus, doubts remain as to which MIOL design would offer the best visual performance and patient satisfaction in patients with retinal disease.

Contraindications for MIOLs
Several doubts and contraindications for MIOL implantation currently exist. These include corneal aberrations, particularly coma or cone, which might result in a decreased contrast sensitivity and dysphotopsia. IOL decentration relative to the pupil center leads to an increase in high-order aberrations and diminished objective contrast discrimination. Thus, an asymmetric capsulorrhexis, The age-related decrease in CS was found only at haptics deformation, or finally IOL subluxation might disqualify a patient from an MIOL. As the IOL pseudoexfoliation syndrome is correlated with zonular instability, centration in these patients is questionable. Patients with a large pupil, postoperative ametropia, and astigmatism or who have developed posterior capsule opacification are at risk of dissatisfaction after MIOL implantation [59,60]. Multifocals are strictly disadvised in retinitis pigmentosa and Stargardt's disease, while diabetic retinopathy, age-related macular degeneration, and epiretinal membranes are relative contraindications [61]. In light of this, a thoughtful approach would be recommended in patients with neuro-ophthalmological conditions (e.g., strabismus, Horner's syndrome) or glaucomatous visual field defects [62,63].

Evidence on MIOLs and retinal diseases
Only two studies assessed the visual outcome of MIOLs in patients with concurrent retinal diseases (Table 3). Kamath et al. [64] reported that patients with concurrent eye diseases including age-related macular degeneration, glaucoma, or diabetic retinopathy benefited from the multifocality of an IOL. The MIOL arm of the study comprised 81 eyes (70 patients) and the monofocal arm 52 eyes (41 patients). Distance visual acuities were similar in the monofocal IOL and MIOL groups, while uncorrected near visual acuity (UNVA) was significantly better in the MIOL group. Patients who had a monofocal IOL in one eye and a MIOL (Array, Abbott Medical Optics Santa Ana, CA) in the fellow eye reported greater subjective satisfaction with the MIOL; however, 3 of these 11 patients had more advanced pathology in the eye with the monofocal IOL, making it difficult to interpret the significance of this finding. However, no clear definition of "more advanced pathology" was given by the authors.
Our study demonstrated that the results are divergent, even when they only include normal eyes without concurrent retinal diseases. Nevertheless, one might question whether the presence of eye diseases should be a decisive reason to categorically advise against MIOLs. Gayton et al. [65] proposed implantation of Acrysof Restor (Alcon, Fort Worth, TX) targeting − 2.0D in eyes with agerelated macular degeneration and corrected distance visual Older and younger observers did not differ in ability to see targets with fine structure (high spatial frequencies); older observers were only one-third as sensitive to targets with coarse structure (low spatial frequencies) as were younger observers. Older observers were also less able than younger observers to see moving targets Derefeldt et al.
1979 [26] 10 children ( cpd cycles per degree, CS contrast sensitivity Monofocal better at all spatial frequencies. Diffractive optics and aspheric profiles showed a non-statistically significant trend to perform better in mesopic conditions. Near CS was lower for refractive, distance dominant lens designs, particularly at medium to high spatial frequencies Tan et al. 2014 [42] Akreos AO (Bausch & Lomb) vs. ZMA00 (AMO) vs. Tetraflex (Lenstec) (total n = 128 eyes) CS visual acuity was measured at contrast levels: 100%, 25%, 10%, and 5% No significant differences of the CS visual acuity were present among the three groups at 3 months after surgery Yamauchi et al.
2013 [43] Tecnis ZA9003/ZCB00 (AMO) vs. Mean contrast sensitivity was better for the monofocal IOL group than for the MIOLs. Patients assigned to TwinSet had less favorable contrast sensitivity scores compared to newer design multifocals Cillino et al.
2008 [48] CS at 1.5, 3, 6, 12, and 18 cpd All groups behaved similarly. At 3 cpd, the monofocal IOL (AR40) and diffractive acuity (CDVA) of 20/50 or worse. This approach is particularly interesting as it provided an uncorrected near + 5.2D addition. The CDVA improved in 14 out of 20 eyes (70%) and the UNVA in 18 out of 20 (90%) eyes. Particularly for patients receiving MIOLs, evaluation of vision-related quality of life shoud be considered [66]. Within this study patients

Conclusions
We were unable to find evidence suggesting that patients with macular diseases should be advised against MIOLs. Several contraindications for MIOLs in patients with retinal diseases have a hypothetical character and are not evidence-based. More research is needed especially to address the effect of MIOLs on CS, visual functions, and patient activities such as orientation, mobility, and reading in various retinal pathologies.

Compliance with ethical standards
Conflict of interest Dr. Grzybowski reports non-financial support from Bayer, non-financial support from Novartis, non-financial support from Alcon, personal fees and non-financial support from Valeant, grants from Zeiss, personal fees and non-financial support from Santen, outside the submitted work. Dr. Kanclerz reports non-financial support from Visim and Optopol Technology. Dr. Tuuminen reports non-financial support from Bayer, personal fees from Novartis, personal fees from Alcon, personal fees from Allergan, non-financial support from Thea, outside the submitted work.
Ethical approval This article does not contain any studies with human participants performed by any of the authors.
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