Patient-Reported Outcomes of Visual Disturbances with a Trifocal Intraocular Lens: A Meta-Analysis

Abstract

Introduction

Diffractive trifocal intraocular lenses (IOLs) provide good vision at distance, intermediate, and near, but can also cause positive dysphotopsias. This meta-analysis pooled published evidence on visual disturbances after bilateral implantation of the PanOptix (TFNTXX) IOL for patients undergoing cataract surgery.

Method

A systematic literature search was conducted in PubMed and congress presentations from April 2021 to December 2022 to identify studies with patient-reported outcomes on the incidence of visual disturbances (starbursts, halos, glare) post bilateral implantation of PanOptix IOL during cataract surgery. Random-effects meta-analysis was performed to generate pooled proportions for patient-reported visual disturbances with a 95% confidence interval [CI].

Results

Eleven unique studies were included, spanning 580 patients with bilateral implantation of PanOptix IOL from 10 countries with 1 to 12 months follow-up. In summary, 33.6% of patients with bilateral PanOptix implantation experienced glare, 43.9% experienced halos, and 30.4% experienced starbursts. Among these patients, small percentages reported severe glare (2.9%), severe halos (5.4%), and severe starbursts (3.4%). Only 0.8%, 1.4%, and 2.6% of patients found glare, halos, and starbursts, respectively, to be very bothersome.

Conclusion

Halos are the most frequently reported visual disturbances. However, the likelihood of experiencing severe and/or very bothersome visual disturbances (halos, glare, starbursts) is approximately 5% and 3%, respectively, after bilateral implantation of PanOptix IOL. These findings should inform clinical decision-making and treatment choices when selecting the most appropriate IOL implant for cataract surgery.

Key Summary Points

Why carry out this study?

Studies have reported high rates of visual disturbances among patients implanted with PanOptix (TFNTXX) intraocular lens (IOL), but between-study heterogeneity exists, making it difficult for surgeons and patients to make an informed choice regarding different IOLs.

A meta-analysis was conducted to show the pooled incidence of visual disturbances for the PanOptix IOL during cataract surgery.

What was learned from this study?

This meta-analysis of 11 unique studies worldwide found that less than 5% and 3% of patients experienced severe and very bothersome visual disturbances, respectively, following bilateral implantation of the PanOptix IOL during cataract surgery.

Halos was the most prominent form of visual disturbance observed, with only 1–5% of patients reporting it as bothersome or very severe photic phenomena.

These findings can help clinicians and patients make informed decisions regarding treatment options and management strategies that prioritize patient comfort and vision-related quality of life while correcting presbyopia during cataract surgery.

Introduction

With a global age-standardized prevalence rate of 17.2%, cataracts are the leading cause of vision impairment and blindness globally [1, 2]. In addition to decreased vision, patients with cataract have presbyopia, an age-related impairment in which the eye’s natural crystalline lens loses its ability to accommodate and see up close. Presbyopia is a common condition in patients who are older and seeking cataract surgery [3]. Uncorrected presbyopia reduces vision-related quality of life in patients and significantly impacts their activities of daily living such as reading, writing, threading needles, using mobile phones, etc. [3].

One option to restore vision for individuals with presbyopia and cataracts is to implant a multifocal or extended depth of focus intraocular lens (IOL) during cataract surgery. Unlike monofocal IOLs, which enable patients to see clearly at a fixed distance only, multifocal presbyopia-correcting IOLs provide a full range of vision from distance to near [4–6].

Trifocal IOLs, in particular, have been shown to deliver higher rates of patient satisfaction [6–8] and complete spectacle independence [9] compared to monofocal IOLs [10, 11] and may provide a greater improvement in vision-related quality of life [12]. However, the higher incidence of photic phenomena or visual disturbances associated with multifocal IOLs has limited their use [10, 13]. Moreover, reported rates of visual disturbances show significant variability across different studies, making it difficult for surgeons and patients to make an informed choice regarding different IOLs. This meta-analysis was conducted to better characterize the real-world rate of visual disturbances after bilateral implantation of the diffractive trifocal IOL (TFNTXX, AcrySof IQ PanOptix) in patients undergoing cataract surgery.

Methods

This meta-analysis was conducted in accordance with the principles described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [14, 15].

Search Strategies

A literature search was conducted in PubMed for publications from 1 April 2021 to 31 December 2022 without any language limitations. Papers that were published in cataract and ophthalmology congresses (American Academy of Ophthalmology (AAO); Asia Pacific Association of Cataract and Refractive Surgeons (APACRS); Asia Pacific Academy of Ophthalmology (APAO); American Society of Cataract and Refractive Surgery (ASCRS); European Society of Cataract and Refractive Surgeons (ESCRS) from the years 2021 and 2022 were also searched. In addition, the manufacturer’s (Alcon) internal clinical trial database was searched to include data from studies not in the public domain.

Search terms included generic and brand names of IOLs, patient-reported visual outcomes, and clinical outcomes. The records resulting from the initial search were refined to include only studies reporting patient-reported outcomes after bilateral implantation of the PanOptix IOL.

Eligibility Criteria

We included all clinical controlled (randomized or nonrandomized) and observational studies that assessed patient-reported visual disturbances after bilateral implantation of the PanOptix IOL. Studies that had follow-ups of at least 1 month were included. We excluded studies that reported preclinical or clinical outcomes without patient-reported outcomes, animal studies, duplicate studies (peer-reviewed publications superseded congress papers), patients implanted with mix-and-match IOLs, unilateral implantation of PanOptix IOL, reviews, and IOLs other than the PanOptix.

Search Process

One reviewer (SK) searched and scanned the titles and abstracts (phase 1) and read full-text articles (phase 2). If the abstracts were unavailable for congress papers, posters or presentations were scanned. Studies that met the inclusion and exclusion criteria were marked on a spreadsheet with reasons. A second reviewer, Sandra Hänninen (SH), quality-checked the screening processes (both phases), and any discrepancies during the processes were resolved through discussion. The selection of the studies is detailed in the PRISMA flowchart (Fig. 1).

Fig. 1.

PRISMA flowchart. IOLs Intraocular lenses, AAO American Academy of Ophthalmology, APACRS Asia Pacific Association of Cataract and Refractive Surgeons, APAO Asia Pacific Academy of Ophthalmology, ASCRS American Society of Cataract and Refractive Surgery, ESCRS European Society of Cataract and Refractive Surgeons, FDA SSED Food and Drug Administration, Summary of the safety and effectiveness data

Data Extraction and Management

Like the selection process, one reviewer (SK) extracted the data from the included studies, and another (SH) checked the extraction quality. Data were extracted into a spreadsheet and included study characteristics such as study sponsor, design, location, objectives, settings, population, and conclusion. The spreadsheet also included the patients’ baseline information and patient-reported outcomes.

Statistical Analysis

Continuous variables were reported as mean and standard deviation (SD), and categorical variables were reported as proportions (%). Published evidence was synthesized on patient-reported visual disturbances in patients undergoing bilateral implantation of PanOptix IOL. Proportions reported as “never” were reversed and used for the analysis. Further, the severity and bothersomeness of visual disturbances were included if they were assessed using a standardized grading scale, ranging from “never” to “severe” or “very much bothered”; only the “severe” and “very much bothered” proportions were included in the analysis.

The frequentist meta-analysis function “metaprop” from R package meta [16] was used to obtain pooled proportions for patient-reported outcomes with 95% confidence intervals [95% CI]. The meta-analytical methods included the inverse variance method and the Freeman–Tukey double arcsine transformation, which does not require a continuity correction and therefore stabilizes variances [17].

Statistical heterogeneity was assessed using the DerSimonian–Laird estimator of between-study variance (τ²) and the I² statistic. Heterogeneity with a 50% or higher score indicated substantial heterogeneity [18–20]. Therefore, the random effect model was used to analyze pooled estimates. A p value less than 0.05 was considered statistically significant.

Ethical Approval

This article is based on previously conducted studies and does not contain new studies with human participants or animals performed by any of the authors.

Results

Patients and Studies

A total of 774 studies were identified from the initial search (220 from PubMed and 554 from the congresses). After screening the title and abstract, 517 studies were removed. Out of 251 studies left, 82 studies reported outcomes for PanOptix IOL. After the full-text screening and removal of duplicate reporting, 10 unique studies remained eligible for inclusion in the final analysis from PubMed and congresses. For congress papers that were published as scientific peer-reviewed articles, only the final articles were included. Additionally, we included one clinical study report that reported patient outcomes for PanOptix IOL that the US Food and Drug Administration published [21] and its additional information from Alcon’s internal clinical study report [22]. In total, 11 studies were included in our final analysis. The screening process with reasons for exclusion is presented in Fig. 1.

The included studies were seven peer-reviewed papers [23–29], three congress papers [30–32], and the clinical study report [21, 22]. All studies reported on the incidence of glare and 10 reported on the incidence of halos [22–29, 31, 32] and starbursts [22–25, 27–32]. Six studies reported the severity of visual disturbances [21, 23–25, 29, 32] and five reported the bothersomeness of visual disturbances [21, 23, 25, 29, 31]. In terms of study design, six studies were prospective observational [23, 26–28, 31, 32], four were randomized controlled trials [24, 25, 29, 30], and one was a non-randomized controlled trial [21, 22]. The follow-up periods ranged from 1 to more than 12 months, with a weighted mean time of 6 months. In terms of study location, three studies were conducted in the USA [21, 22, 28, 30], one each in Australia [23], Portugal [25], and Kuwait [29], and the other two studies were conducted across multiple countries—one in Germany, Spain, Philippines, New Zealand, and Singapore [24], and the other in Australia, Chile, and Europe [26]. The other three studies did not report the location [27, 31, 32]. The study characteristics for each study are detailed in Table 1.

Table 1.

Characteristics of included studies

Study/Author	Design	Follow-up in months	Countries	Measures	Patients (N = 580)	Male	Age in years (SD)
FDA SSED [21]a; IDE CSR [22]b	Prospective, multicenter, non-randomized, parallel-group, confirmatory trial	6	USA	QUVID	127e	34.1%	65.8 (7.3)
Ackerman et al. [23]c	Prospective cohort study	3	Australia	QoV	22	NR	NR
Dick et al. [24]c	Prospective, randomized, comparative study	3	Germany, Spain, Philippines, New Zealand, and Singapore	Nondirected patients reports	52	41.5%	65.6 (7.8)
Ferreira et al. [25]c	Prospective, randomized, comparative study	3	Portugal	QoV	30	NR	61.1 (6.0)
Lapid-Gortzak et al. [26]c	Prospective, multicenter, single-arm, nonrandomized,	12	Australia, Chile, and Europe	NS	145	39.3%	68.9
Mohaseb et al. [27]c	Prospective, single-arm	3	NR	NS	70	44%	70.8 (7.6)
Sandoval et al. [28]c	Prospective, single-arm, non-interventional	3	USA	QUVID	28	25%	68 (8.0)
Torky et al. [29]c	Prospective, randomized study	6	Kuwait	NS	26	42.3%	59.4 (6.1)
Modi [30]d	Prospective, randomized study	3	USA	NS	24	NR	NR
Mueller et al. [31]d	Prospective, single center, non-randomized, open-label observational clinical study	6	NR	QUVID	17	NR	63 (6.6)
Nattis et al. [32]d	Prospective, observational Study	1	NR	QoV	39	33%	65 (9.8)
Weighted mean		6				37.7%	66.7 (7.5)

NR not reported, QoV Quality of Vision, QUVID Questionnaire for Visual Disturbances, NS not specified, SD standard deviation

^aFDA SSED Food and Drug Administration, Summary of the safety and effectiveness data

^bIDE CSR Investigational Device Exemption Clinical Study Report from Alcon

^cPeer-reviewed publication

^dCongress paper

^e127 patients for halos, 126 patients for glare, 125 patients for starbursts

All patients (N = 580, weighted mean age 67 years) were bilaterally implanted. Eight studies [21–23, 25, 26, 28–30, 32] included patients who were undergoing cataract surgery. However, two studies [24, 27] included patients with bilateral cataract and/or clear lens extraction, while another study [31] included patients who had prior myopic PRK or LASIK and received PanOptix IOL bilaterally at the time of cataract surgery. While three studies did not report exclusion criteria [26, 30, 31], the other studies excluded patients with ocular pathology or diseases.

The review incorporated several subjective assessments of patient-related outcomes associated with visual disturbances. The Questionnaire for Visual disturbances (QUVID) was utilized in three studies [21, 22, 28, 31], and the Quality of Vision questionnaire (QoV) was applied in three studies [23, 25, 32]. Additionally, nondirected patient reports were used in one study [24]. Four studies did not specify the measure utilized [26, 27, 29, 30].

Outcomes

For the endpoint of glare, the meta-analysis of 11 studies (579 patients in total) estimated 33.6% (95% CI 16.9–52.5%) incidence. The heterogeneity (I²) in this analysis was high (95%) (Fig. 2a). Based on six studies (295 patients) reporting severe glare, its estimated incidence was 2.9% (95% CI 0.2–7.5%, I² = 59%) (Fig. 2b). Five studies (221 patients) were included for the analysis of “very bothersome” glare, with an overall incidence estimate of 0.8% (95% CI 0.0–3.1%, I² = 0%) (Fig. 2c).

Fig. 2.

a Glare after cataract surgery with bilateral implantation of PanOptix (TFNTXX) intraocular lens (IOL): Forest plot. b Severe glare after cataract surgery with bilateral implantation of PanOptix (TFNTXX) IOL: Forest plot. c “Very bothersome” glare after cataract surgery with bilateral implantation of PanOptix (TFNTXX) IOL: Forest plot. IDE CSR Investigational Device Exemption Clinical Study Report, CI Confidence interval, FDA SSED Food and Drug Administration, Summary of the safety and effectiveness data

The incidence of halos, pooled from 10 studies (556 patients) was 43.9% (95% CI 21.7–67.3%) with high heterogeneity of 97% (Fig. 3a). Based on six studies (296 patients), 5.4% (95% CI 1.5–10.8%) experienced severe halos (I² = 56%) (Fig. 3b). The “very bothersome” halos were reported in five studies (222 patients), with a pooled incidence of 1.4% (95% CI 0.0–3.9%, I² = 0%) (Fig. 3c).

Fig. 3.

a Halos after cataract surgery with bilateral implantation of PanOptix (TFNTXX) IOL: Forest plot. b Severe halos after cataract surgery with bilateral implantation of PanOptix (TFNTXX) IOL: Forest plot. c “Very bothersome” halos after cataract surgery with bilateral implantation of PanOptix (TFNTXX) IOL: Forest plot. IDE CSR Investigational Device Exemption Clinical Study Report, CI Confidence interval, FDA SSED Food and Drug Administration, Summary of the safety and effectiveness data

Among 10 studies (433 patients), 30.4% (95% CI 12.4–52.0%) of patients experienced starbursts. The heterogeneity was high, 95% (Fig. 4a). Additionally, six studies (294 patients) contributed to the estimation of an incidence of 3.4% (95% CI 0.0–11.2%) of severe starbursts (I² = 81%) (Fig. 4b) and 2.6% (95% CI 0.6–5.6%) incidence for “very bothersome” starbursts, as reported in five studies involving 220 patients (I² = 0%) (Fig. 4c).

Fig. 4.

a Starbursts after cataract surgery with bilateral implantation of PanOptix (TFNTXX) IOL: Forest plot. b Severe starbursts after cataract surgery with bilateral implantation of PanOptix (TFNTXX) IOL: Forest plot. c “Very bothersome” starbursts after cataract surgery with bilateral implantation of PanOptix (TFNTXX) IOL: Forest plot. IDE CSR Investigational Device Exemption Clinical Study Report, CI Confidence interval, FDA SSED Food and Drug Administration, Summary of the safety and effectiveness data

Discussion

In this study, we pooled the evidence related to the incidence of postoperative visual disturbance outcomes in patients receiving bilateral PanOptix IOL during cataract surgery. Our findings show that halos were the most frequently reported visual disturbances (incidence 44%), followed by glare (34%) and starbursts (30%). However, despite the occurrence of visual disturbances, only 5% or fewer patients reported severe visual disturbances and fewer than 3% patients were “very much bothered” by visual disturbances [25, 29, 33–35].

Like our results, a higher incidence of halos in trifocal IOLs was also reported in previous studies [24, 25, 33–35]. A meta-analysis comparing trifocal and multifocal-EDOF IOLs also suggested that trifocal IOLs were 32% more likely to generate a halo effect [36]. Further, diffractive trifocal toric IOLs have reported significant levels of size and intensity of halos and glare [37]. However, any disruption of the light passing through the optical axis could result in subjective misinterpretation and different types of visual sensations, with halo and glare effects being the most reported [38].

The increased incidence of visual disturbances is a common feature of diffractive multifocal IOLs [39, 40]. However, the severity of visual disturbances can decrease from 1 to 3 or 6 months after surgery as patients with trifocal IOL experienced less severe halos and glare compared with baseline data [33, 40, 41]. This is likely due to the process of neuroadaptation, whereby patients gradually undergo neuroadaptation to photic phenomena following surgery [23]. It is worth noting that in some studies included in this research [23–25, 27, 28, 30, 32], severe or bothersome visual disturbances were reported at relatively short follow-up periods; however, with the neuroadaptation process, the long-term risk for patients could be lower. Authors believe there is a need for new clinical studies with longer follow-up periods to assess the impact of neuroadaptation on the resolution of visual disturbances.

The meta-analysis presented here did not include any comparators, as only three comparative studies were identified during the search period in which PanOptix was compared with other trifocal IOLs [24, 25, 29]. The limited number of comparative studies made it difficult to conduct a head-to-head meta-analysis because of the potentially unreliable estimates that would be generated. Additionally, the differences in cohort sizes and population heterogeneity led us to refrain from conducting a head-to-head meta-analysis. Ferreira et al. [25] compared PanOptix IOL with two other trifocal IOLs, i.e., Synergy and Finevision, and found no statistically significant differences in terms of occurrence, severity, and bothersomeness of glare, halos, and starbursts. However, Dick et al. [24] found higher rate of starbursts, night glare and severe halos with Synergy than PanOptix; however, statistically significant differences between then groups were not reported. Torky et al. [29] conducted a prospective randomized controlled trial and reported that there were no statistically significant differences in the frequency, severity, and degree of bother of visual disturbances when PanOptix, and ATLISA Tri trifocal IOLs were compared with extended-range-of-vision IOL, Symfony [29]. However, Modi [30] found that the incidence of starbursts (89.5% vs 45.5%) and incidence of glare (63.2% vs 27.3%) were higher in extended-range-of-vision IOL, Symfony, compared to trifocal IOL, PanOptix IOL. Further research (comparative trials with a large sample size as well as longitudinal studies) is required to draw any conclusions.

To our knowledge, this meta-analysis is the first to show the pooled incidence of visual disturbances for the PanOptix IOL. Meta-analysis is a statistical technique that involves aggregating findings from multiple independent studies. Integrating data from various sources enhances the accuracy of results, providing a more comprehensive understanding than what can be obtained from individual studies alone [15].

However, this study has some limitations that should be considered when interpreting and applying the findings. First, studies included data only from April 2021 to December 2022. Second, only six studies included a validated questionnaire: three studies with QUVID and three with QoV. Third, some of the studies included patients who had prior LASIK or PRK surgery [31] as well as patients with clear lens extraction [24, 27], which could skew the visual disturbances data towards a higher incidence. Fourth, this review did not include a quality appraisal. However, we conducted a comprehensive systematic search with clearly defined inclusion and exclusion criteria for selecting studies. We also used a standardized method for extracting data from the studies to minimize bias. Fifth, the statistical heterogeneity across studies in this meta-analysis was high except for “very bothersome” visual disturbances, indicating diversity among the included study populations (e.g., variations in follow-up time, study location, and assessment tools). Therefore, the random model for all data analyses was chosen. Lastly, we included three studies from congress presentations only, which may have limited detail. However, we believe the proportions reported in these studies were sufficient to include in the analysis.

Conclusion

This meta-analysis of 11 unique studies (580 patients) demonstrated that the risks of “severe”’ and “very bothersome” visual disturbances (halos, glare, starbursts) are approximately 5% and 3%, respectively, in patients undergoing bilateral implantation of the PanOptix IOL for cataract surgery. These findings should better inform clinical decision-making and treatment choices when selecting a presbyopia-correcting IOL for cataract surgery. Future studies should utilize validated questionnaires to more accurately explore visual disturbances with longer follow-up periods.

Author Contributions

Study—management (Erkki Soini, Mukesh Dhariwal), conceptualization and design (Mukesh Dhariwal, Erkki Soini, Dagny Zhu, Suyen Karki, Christian Asseburg); data—acquisition and management (Suyen Karki), interpretation (all); analysis—design (Suyen Karki, Christian Asseburg), implementation (Suyen Karki), interpretation (all); manuscript—initial drafting (Suyen Karki), critical revision (all), final approval (all); supervision (Erkki Soini, Mukesh Dhariwal); funding (Mukesh Dhariwal, Erkki Soini).

Funding

Funding for this study and Rapid Service Fee were provided by Alcon Vision LLC, Fort Worth, Texas, USA.

Data Availability

Data sharing does not apply to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

Dagny Zhu has received consulting fees and honorariums for participation in advisory boards from Alcon and Johnson & Johnson, as well as a speaker honorarium from Alcon. Alcon is a manufacturer of multiple IOLs. Mukesh Dhariwal is an employee of Alcon. ESiOR Oy received consulting fees from Alcon to conduct the study. ESiOR Oy is an expert company that carries out health economics and outcomes research HEOR, data science and evidence generation, real-world data and biobank studies, health technology assessment HTA, market access, and other services as well as provides certified secure processing environment SPESiOR® for several institutions and projects, including also the producers and marketers of IOLs. Erkki Soini is a partner of ESiOR Oy, and chairman of the board at Kuopio Health cooperative. Suyen Karki, Christian Asseburg, and Erkki Soini are employed by ESiOR Oy. Dagny Zhu, Mukesh Dhariwal, Erkki Soini, Suyen Karki and Christian Asseburg have no other conflicts of interest related to this work.

Ethical Approval

This article is based on previously conducted studies and does not contain new studies with human participants or animals performed by any of the authors.