Should enhanced monofocal intraocular lenses be the standard of care? An evidence-based appraisal by the ESCRS Functional Vision Working Group

The use of a monofocal intraocular lens (IOL) is considered as the standard of care (SoC) in cataract surgery in terms of the IOL to implant (Supplementary Material, available at https://links.lww.com/JRS/B141). The main reason for this widely accepted statement is that this was the first type of IOL developed.1 However, a specific mode of proceeding in healthcare can be considered as SoC when some specific conditions are met: (1) agreement with local and national legal regulations; (2) agreement with authoritative clinical guidelines: clinical care standards, preferred practice patterns, clinical practice guidelines, or standard treatment guidelines; (3) agreement with professional guidelines: clinical care standards, preferred practice patterns, clinical practice guidelines, standard treatment guidelines, and consensus documents; (4) support from professional organizations: position papers, statements, and consensus documents; And (5) scientific evidence: clinical and patient-reported outcomes and cost-effectiveness studies.2,3 To this date, there are different guidelines and statements on cataract surgery, but no recommendation regarding the selection of the IOL to implant is provided in any of them. Indeed, there are no authoritative clinical or professional guidelines on how to select the type of IOL to implant. However, advances in IOL optics have been introduced in past few years, leading to a more optimized visual rehabilitation after cataract surgery, such as the development of enhanced monofocal IOLs, that are also designated in some contexts as monofocal plus IOLs.4,5 These enhanced monofocal IOLs include some optical modifications to provide an efficacious correction for distance vision while providing an enhanced intermediate visual function. This full distance vision combined with an improved intermediate vision can be enough to provide the patients with a functional vision, allowing overcoming most of their limitations in terms of activities of daily living.6 These modified monofocal IOLs do not fully meet 1 or more effectiveness end points that should be met according to the American National Standard Institute Z80.35-2018 for classifying them as extended depth-of-focus (EDOF) IOLs: (1) To demonstrate a statistical superiority over a control monofocal group on mean, monocular photopic distance-corrected intermediate visual acuity at 66 cm. (2) To demonstrate at least 0.5-diopter greater monocular photopic negative lens induced distance-corrected depth of focus compared with the monofocal control IOL at 0.2 logMAR visual acuity threshold. (3) The median monocular distance-corrected photopic intermediate visual acuity at 66 cm must be at least 0.2 logMAR. (4) The mean monocular photopic best corrected distance acuity for the EDOF IOL must be statistically noninferior to the control monofocal group using a noninferiority margin of 0.1 logMAR.7,8 Considering the potential superiority of enhanced monofocal IOLs over conventional monofocal IOLs in terms of intermediate visual acuity and the equivalence between IOL types in terms of safety, the use of these enhanced monofocal IOLs as SoC in cataract surgery should be discussed. For this purpose, the first step is to confirm whether there is enough scientific evidence confirming the clinical superiority of enhanced monofocal over conventional monofocal IOLs. It should be considered that the level of bias and the consistency of such evidence are critical to establish clinical recommendations. Randomized clinical trials (RCTs) and meta-analysis of RCT data are the gold standard for evaluating the safety and effectiveness of an intervention, providing the highest quality level I evidence according to the hierarchy of evidence defined by the Oxford Centre for Evidence-Based Medicine.9 The purpose of this special report was to evaluate the scientific evidence of the use of enhanced monofocal IOL implantation in cataract surgery in comparison with monofocal IOL visual performance. A literature review was performed on PubMed, Scopus, and Web of Science to analyze the level of scientific evidence on enhanced monofocal IOLs. A search equation was conducted in PubMeD (date May 31, 2023, revised March 22, 2023) with the following terms related to the several types of enhanced monofocal IOLs according to Fernandez et al. (2023) and the latest developments: Acunex or Lentis QUANTUM (Teleon Surg.); EVOLUX (Sifi Medtech Srl); Extend HP (Hanita Lenses); TECNIS Eyhance (Jonhson & Jonhson Vision); IsoPure (Physiol S.A.); RayOne EMV (Rayner Intraocular Lenses Ltd.); Vivinex Impress (Hoya Corp.); Xact ME4 (Santen GmbH); ZOE (OphthalmoPro GmbH); and Aspire (Bausch & Lomb, Inc.).5 Search results showed a total of 3 reviews and 66 articles from the primary literature ranging from 2020 to 2024. Screening of abstracts resulted in the exclusion of 28 publications not meeting the main purpose, that is, studies not comparing conventional monofocal with enhanced monofocal IOLs (N = 22), studies evaluating the clinical outcomes of enhanced monofocal IOLs in pathological eyes (N = 2), research studies in which the visual performance analysis was not the main purpose (N = 3), or investigations in which the visual performance was not measured under standard conditions (N = 1). In addition, 12 publications referred to in vitro measurements on the optical bench. Finally, a total of 1 meta-analysis and systematic review, 1 meta-analysis, 1 scoping review, and 19 clinical studies were considered for analysis (Table 1).5,10–34 Table 1. - List of peer-reviewed publications analyzed Study Study type IOLs (enhanced monofocal vs monofocal) Follow-up Summary of VA results (enhanced monofocal vs monofocal, P value) Giglio et al. (2024)12 Randomized clinical trial Eyhance ICB00 vs TECNIS PCB00 or Clareon CNA0T0 3 mo Bino UDVA: −0.03 ± 0.07 vs −0.05 ± 0.06 (P = .259)Bino CDVA: −0.07 ± 0.05 vs −0.08 ± 0.04 (P = .812)Bino UIVA: 0.17 ± 0.12 vs 0.32 ± 0.11 (P < .001)Bino DCIVA: 0.13 ± 0.11 vs 0.29 ± 0.01 (P < .001) Singh et al. (2024)13 Prospective comparative study Eyhance ICB00 vs TECNIS PCB00 3 mo Mono UDVA: 0.11 ± 0.11 vs 0.12 ± 0.11 (P = .92)Mono CDVA: 0.00 ± 0.13 vs 0.01 ± 0.02 (P = .15)Mono UIVA: 0.32 ± 0.11 vs 0.50 ± 0.11 (P < .001) Negishi et al. (2023)14 Prospective comparative study Eyhance ICB00 vs TECNIS PCB00 1 mo Mono UDVA: 0.25 ± 0.29 vs 0.36 ± 0.41 (P = .492)Mono CDVA: −0.05 ± 0.07 vs −0.07 ± 0.03 (P = .625)Bino DCIVA: 0.11 ± 0.19 vs 0.27 ± 0.15 (P = .034) Ang et al. (2023)15 Randomized clinical trial IsoPure vs Micropure 4-6 mo Bino UDVA: 0.00 ± 0.07 vs −0.04 ± 0.07Bino CDVA: −0.05 ± 0.07 vs −0.07 ± 0.07Bino UIVA: 0.10 ± 0.12 vs 0.19 ± 0.13Bino DCIVA: 0.11 ± 0.11 vs 0.20 ± 0.11 Gigon et al. (2023)16 Retrospective comparative study Eyhance ICB00 vs TECNIS PCB00 12 mo UDVA binocular: Approx. 0.00 vs 0.00 (P > .05)CDVA binocular: Approx. 0.00 vs 0.00 (P > .05)UIVA binocular: Approx. 0.20 vs 0.30 (P > .05)CIVA binocular: Approx. 0.20 vs 0.40 (P < .05)UNVA binocular: Approx. 0.10 vs 0.30 (P > .05)CNVA binocular: Approx. 0.10 vs 0.30 (P < .05) Goslings et al. (2023)17 Randomized clinical trial Eyhance ICB00 vs Vivinex iSert 3 mo UDVA binocular: 0.01 ± 0.11 vs 0.00 ± 0.08 (P = .685)CDVA binocular: −0.05 ± 0.09 vs −0.08 ± 0.07 (P = .752)UIVA binocular: 0.12 ± 0.11 vs 0.22 ± 0.12 (P = .001)DCIVA binocular: 0.12 ± 0.11 vs 0.24 ± 0.10 (P < .001) Pérez-Sanz et al. (2023)18 Randomized clinical trial IsoPure vs Micropure 3 mo Mono UDVA: 0.04 ± 0.13 vs 0.01 ± 0.06 (P = .868)Mono CDVA: 0.00 ± 0.06 vs −0.04 ± 0.04 (P = .019) Beltraminelli et al. (2023)19 Retrospective comparative study Eyhance DIB00 vs Acrysof SN60WF or TECNIS DCB00 3 mo Bino UDVA: Approx. 0.10 vs 0.10 (P = .81)Bino UIVA: Approx. 0.10 vs 0.20 (P < .001)Bino UNVA: Approx. 0.35 vs 0.50 (P < .001) Choi et al. (2023)20 Randomized clinical trial Eyhance ICB00 vs TECNIS ZCB00 3 mo Bino UDVA: 0.03 ± 0.05 vs 0.07 ± 0.09 (P = .002)Bino CDVA: 0.01 ± 0.03 vs 0.04 ± 0.07 (P = .146)Bino UIVA: 0.04 ± 0.05 vs 0.10 ± 0.14 (P = .026)Bino UNVA: 0.14 ± 0.13 vs 0.29 ± 0.14 (P < .001) Garzón et al. (2022)21 Randomized clinical trial Eyhance ICB00 vs TECNIS ZCB00 1 mo Mono UDVA: 0.16 ± 0.24 vs 0.13 ± 0.23 (P > .05)Mono CDVA: 0.02 ± 0.05 vs 0.01 ± 0.04 (P > .05) Steinmuller et al. (2022)22 Prospective comparative study Eyhance ICB00 vs TECNIS ZCB00 3 mo Bino UDVA: −0.12 ± 0.10 vs −0.13 ± 0.10 (P = .706)Bino CDVA: −0.20 ± 0.08 vs −0.19 ± 0.09 (P = .912)Bino UIVA: −0.04 ± 0.06 vs 0.07 ± 0.17 (P < .001)Bino CIVA: 0.03 ± 0.13 vs 0.24 ± 0.11 (P < .001)Bino UNVA: 0.08 ± 0.10 vs 0.28 ± 0.20 (P = .003)Bino CNVA: 0.19 ± 0.16 vs 0.43 ± 0.15 (P < .001) Bova et al. (2022)23 Retrospective comparative study IsoPure 1.2.3 + vs TECNIS PCB00 12 mo Bino UDVA: 0.03 ± 0.04 vs 0.03 ± 0.06 (P = .89)Bino CDVA: 0.01 ± 0.03 vs 0.01 ± 0.02 (P = .90)Bino UIVA: 0.22 ± 0.06 vs 0.33 ± 0.07 (P < .001)Bino DCIVA: 0.21 ± 0.07 vs 0.34 ± 0.09 (P < .001) Corbeli et al. (2021)24 Prospective comparative study Eyhance ICB00 vs TECNIS ZCB00 6 mo Bino UDVA: 0.01 ± 0.02 vs 0.01 ± 0.03 (P = .453)Bino CDVA: 0.00 ± 0.02 vs 0.01 ± 0.02 (P = .810)Bino UIVA: 0.04 ± 0.04 vs 0.35 ± 0.09 (P < .001)Bino CIVA: 0.01 ± 0.03 vs 0.02 ± 0.03 (P = .130)Bino DCIVA: 0.07 ± 0.06 vs 0.36 ± 0.09 (P < .001)Bino UNVA: 0.28 ± 0.05 vs 0.49 ± 0.06 (P = .020)Bino CNVA: 0.00 ± 0.02 vs 0.00 ± 0.02 (P = .999)Bino DCNVA: 0.31 ± 0.03 vs 0.51 ± 0.07 (P < .001) Lopes et al. (2022)25 Retrospective comparative study Eyhance ICB00 vs TECNIS PCB00 3 mo Bino UDVA: 0.04 ± 0.12 vs 0.01 ± 0.10 (P = .620)Bino CDVA: 0.03 ± 0.09 vs −0.02 ± 0.07 (P = .45)Bino UIVA: 0.17 ± 0.10 vs 0.30 ± 0.13 (P < .001) Huh et al. (2021)26 Retrospective comparative study Eyhance ICB00 vs TECNIS ZCB00 1 mo Bino CDVA: −0.04 ± 0.09 vs −0.05 ± 0.08 (P = .782)Bino UIVA: 0.03 ± 0.06 vs 0.25 ± 0.18 (P < .001)Bino DCIVA: 0.01 ± 0.04 vs 0.13 ± 0.19 (P = .031)Bino UNVA: 0.09 ± 0.14 vs 0.35 ± 0.14 (P < .001)Bino DCNVA: 0.09 ± 0.15 vs 0.20 ± 0.17 (P = .075) Ucar et al. (2021)27 Retrospective comparative study Eyhance ICB00 vs TECNIS ZCB00 6 mo Mono UDVA: 0.07 ± 0.05 vs 0.04 ± 0.05 (P = .270)Mono CDVA: 0.05 ± 0.03 vs 0.03 ± 0.02 (P = .520)Mono UIVA: 0.08 ± 0.07 vs 0.19 ± 0.06 (P = .010)Mono DCIVA: 0.07 ± 0.06 vs 0.17 ± 0.05 (P = .020)Mono CNVA: 0.01 ± 0.02 vs 0.01 ± 0.02 (P = .980)Mono DCNVA: 0.44 ± 0.18 vs 0.57 ± 0.17 (P = .040) Kang et al. (2021)28 Retrospective comparative study Eyhance ICB00 vs TECNIS ZCB00 3 mo Mono UDVA: 0.11 ± 0.10 vs 0.10 ± 0.14 (P = .451)Mono CDVA: 0.04 ± 0.06 vs 0.03 ± 0.06 (P = .215)Mono UIVA: 0.24 ± 0.10 vs 0.34 ± 0.12 (P < .001)Mono UNVA: 0.46 ± 0.14 vs 0.51 ± 0.19 (P = .038) Auffhart et al. (2021)29 Randomized clinical trial Eyhance ICB00 vs TECNIS ZCB00 6 mo Bino UDVA: 0.03 ± 0.12 vs −0.03 ± 0.11 (P > .05)Bino CDVA: −0.06 ± 0.09 vs −0.10 ± 0.08 (P > .05)Bino UIVA: 0.07 ± 0.12 vs 0.17 ± 0.17 (P < .001)Bino DCIVA: 0.09 ± 0.11 vs 0.20 ± 0.13 (P < .001) Cinar et al. (2021)30 Prospective comparative study Eyhance ICB00 vs AcrySof SN60WF 3 mo Mono UDVA: 0.05 ± 0.13 vs 0.05 ± 0.15 (P = .637)Mono CDVA: 0.02 ± 0.02 vs 0.03 ± 0.02 (P = .523)Mono UIVA: 0.31 ± 0.16 vs 0.41 ± 0.12 (P = .001)Mono CIVA: 0.28 ± 0.12 vs 0.38 ± 0.13 (P = .001) Unsal et al. (2020)31 Retrospective comparative study Eyhance ICB00 vs TECNIS ZCB00 1 mo Mono UDVA: 0.04 ± 0.07 vs 0.06 ± 0.08 (P = .630)Mono CDVA: 0.03 ± 0.05 vs 0.02 ± 0.07 (P = .157)Mono UIVA: 0.24 ± 0.16 vs 0.39 ± 0.24 (P = .038)Mono DCIVA: 0.28 ± 0.31 vs 0.43 ± 0.46 (P = .033)Mono DCNVA: 0.55 ± 0.45 vs 0.75 ± 0.80 (P = .502) Yangzes et al. (2020)32 Prospective comparative study Eyhance ICB00 vs TECNIS ZCB00 2 wk Mono UDVA: 0.10 ± 0.13 vs 0.09 ± 0.11 (P = .840)Mono CDVA: 0.02 ± 0.05 vs 0.01 ± 0.04 (P = .638)Mono UIVA: 0.11 ± 0.13 vs 0.25 ± 0.18 (P < .010)Mono CIVA: 0.02 ± 0.06 vs 0.01 ± 0.03 (P = .631)Mono UNVA: 0.43 ± 0.13 vs 0.61 ± 0.16 (P < .010)Mono CNVA: 0.02 ± 0.07 vs 0.08 ± 0.13 (P = .060) Eguileor et al. (2020)33 Prospective comparative study Eyhance ICB00 vs TECNIS ZCB00 1 mo Bino CDVA: −0.05 ± 0.07 vs −0.06 ± 0.07 (P = .736)Bino DCIVA: 0.16 ± 0.12 vs 0.37 ± 0.12 (P < .001) Mencucci et al. (2020)34 Prospective comparative study Eyhance ICB00 vs TECNIS ZCB00 6 mo Bino UDVA: 0.03 ± 0.05 vs 0.04 ± 0.05 (P = .798)Bino CDVA: 0.01 ± 0.04 vs 0.01 ± 0.04 (P > .999)Bino UIVA: 0.16 ± 0.10 vs 0.27 ± 0.06 (P = .021)Bino CIVA: 0.04 ± 0.05 vs 0.06 ± 0.04 (P = .004)Bino DCIVA: 0.15 ± 0.08 vs 0.26 ± 0.04 (P = .382)Bino UNVA: 0.33 ± 0.05 vs 0.38 ± 0.05 (P = .072)Bino CNVA: 0.03 ± 0.05 vs 0.03 ± 0.05 (P = .613)Bino DCNVA: 0.32 ± 0.04 vs 0.37 ± 0.05 (P = .094) In summary, most of the studies reviewed confirmed the superiority of enhanced monofocal IOLs in terms of intermediate visual function over conventional monofocal IOLs, with a maximum level of scientific evidence associated (level Ia) (Table 2). This maximum level has been achieved because several RCTs have supported these findings, being summarized and evidenced in systematic reviews and meta-analyses of such trials. This enhanced intermediate visual function was reached with no distance visual acuity worsening or contrast sensitivity or visual quality deterioration associated. Therefore, enhanced monofocal IOLs provide interchangeable results in terms of distance vision compared with conventional monofocal IOLs.12–34 Table 2. - Summary of the type of scientific evidence available on enhanced monofocal IOLs Evidence N Funding Conflict of interest Meta-analysis 2 — — Systematic reviews 2 — — Randomized controlled trial 7 Giglio et al.12: Unrestricted grant of the IOL company None Ang et al.15: Funded by Beaver-Visitec International, Inc. Grants and personal fees from the IOL company Goslings et al.17: Unrestricted grant of the IOL company None Pérez-Sanz et al.18: No funding None Choi et al.20: Funded by Medical Research Funds from Kangbuk Samsung Hospital None Garzón et al.21: Unrestricted grant of the IOL company None Auffharth et al.29: Funded by the IOL company Grants and personal fees from the IOL companySome authors employees of the IOL company Prospective comparative studies 8 Singh et al.13: No funding None Negishi et al.14: Unrestricted grant of the IOL company Grants and personal fees from the IOL company Steinmuller et al.22: No funding None Corbelli et al.24: No funding None Cinar et al.30: No funding None Yangzes et al.32: No funding None Eguileor et al.33: No funding None Mencucci et al.34: No funding None Retrospective comparative studies 8 Gigon et al.16: No funding None Beltraminelli et al.19: Unrestricted research grant by Bayer AG Switzerland None Bova et al.23: No funding None Lopes et al.25: No funding None Huh et al.26: Supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2019R1A2C1088904) None Ucar et al.27: No funding None Kang et al.28: No funding None Unsal et al.31: No funding None Cost-effectiveness 0 Most of the clinical studies reviewed were focused on the analysis of the functional results obtained with enhanced and conventional monofocal IOLs, including meaningful metrics that affect patients and, even in some cases, patient-reported outcomes measured with validated questionnaires.17 All these results are critical for taking the relevant decision of implanting the enhanced and conventional models of monofocal IOLs. Contrarily, optical bench testing should not be used for clinical decision-making as they do not necessarily reflect the actual behavior in patients, although they can serve as informative about the potential optical behavior of the optics. According to our review, the first condition for establishing the use of enhanced monofocal IOLs as SoC in cataract surgery is accomplished. However, cost-effectiveness studies are still needed and highly recommended to demonstrate that the clinical benefit obtained with enhanced monofocal IOLs is greater than the cost increase compared with conventional monofocal IOLs. In addition, position papers or consensus statements from different eyecare professional organizations are needed to give visibility to the benefit of enhanced monofocal IOLs based on the results of the clinical studies revised. In the future, these documents and data can be used to show the relevance of this potential new SoC in cataract surgery to public institutions.