Performance of Extended Depth of Focus Intraocular Lens in Eyes with Preexisting Retinal Disease

The immediate result of a monofocal intraocular lens (IOL) implantation targeted for distance vision is presbyopia, necessitating patient reliance on glasses for both intermediate and near distances [1]. Current solutions include monovision (implantation of a monofocal IOL in both eyes, one for distance and the other for intermediate/near vision), or a multifocal IOL (MIOL), which attempts to reduce spectacles dependence by providing several images in each eye. MIOLs are not suitable for all patients. Ocular comorbidities, such as retinal or corneal pathologies, ocular surface disease, and amblyopia, are considered contraindications for MIOLs by most surgeons [2]. In addition, some of the patients who qualify for an MIOL experience postoperative photic phenomena, such as haloes and glare [3]. This is of special concern in eyes with retinal pathologies, in which MIOLs could exacerbate visual disturbances of their primary ocular disease.

Another concept of IOL, the extended depth of focus (EDOF) IOL, was introduced. It is designed to achieve continuous uncorrected visual acuity from far to intermediate distances while maintaining a relatively low incidence of haloes and glare. The TECNIS Symfony^® IOL (Johnson and Johnson Vision, New Brunswick, NJ, USA) is one representative of this group. This biconvex lens uses an echelette feature to extend the range of vision combined with a wavefront-designed anterior aspheric surface and a posterior achromatic diffractive surface designed to reduce chromatic aberration for enhanced image contrast [4].

Previous studies have affirmed the results of the EDOF IOL in the general population of cataract patients [4‒9]. In this retrospective study, we aimed to report our experience with the EDOF IOL, including visual function outcomes, spectacles independence, photic phenomena, and patient satisfaction in a group of patients with retinal pathologies who were contraindicated for MIOLs in comparison to healthy control eyes that were implanted with the same IOL.

This study included patients who had unilateral or bilateral EDOF IOL (TECNIS Symfony) implantation during routine cataract surgery, with postoperative manifest refraction of at least 3 weeks after the surgery. All surgeries were performed by a single surgeon (G.K.) in a private practice setting, at the Ein-Tal Eye Center, Tel Aviv, Israel, between January 2015 and April 2022. The study adhered to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of the Meir Medical Center, Kfar Saba, Israel (No. 0046-12-MMC [Meir Medical Center]). Data were collected retrospectively in a case-control study design. As this study was based on retrospective data available in patients’ medical records, it was exempt from obtaining informed consent from its participants by the Institutional Review Board of the Meir Medical Center, Kfar Saba, Israel.

The study group (retinal pathologies) consisted of consecutive patients with either mild dry age-related macular degeneration (AMD) or stable mild epiretinal membrane (ERM). Mild AMD was defined based on the clinical features specified in the Age-related Disease Study (AREDS) classification [10]. Only cases compatible with categories 1 or 2 were included. ERM was graded according to the classification suggested by Hwang et al. [11]. Only cases of ERM with inner retinal thickening and minimal retinal change with no other retinal distortion or intraretinal fluids were included. All the cases were examined and approved for cataract surgery alone by a retinal specialist. The control group consisted of consecutive healthy eyes of patients who underwent cataract surgery with implantation of the EDOF IOL by the same surgeon during the study period.

Exclusion criteria for this study were (1) patients with significant ophthalmic pathology, other than the retinal comorbidities specified above, effecting visual acuity, such as corneal or macular scars and amblyopia; (2) previous refractive surgery; (3) intraoperative and postoperative complications that influence the patients’ visual performance and are not related to the IOL; (4) patients who did not undergo a postoperative examination at least 3 weeks after the surgery; (5) age younger than 18; (6) patients with retinal pathology who required combined operation (pars plana vitrectomy and cataract surgery); and (7) patients with a monofocal IOL in the second eye.

The patients’ medical records were retrospectively reviewed for data regarding medical and ophthalmic history, preoperative ophthalmic bio-macroscopic examination, preoperative biometry using the Lenstar (LS900, Haag-Streit, Koeniz, Switzerland), corneal tomography using the Pentacam Scheimpflug system (Oculus, Optikgerate GmbH, Wetzlar, Germany), and corneal high order aberrations measured by the Pentacam under scotopic lighting conditions. The retrieved surgical data included any surgical complications, the model, and the power of the implanted IOL. Postoperative evaluation included postoperative complications assessment, manifest refraction, and monocular uncorrected visual acuity for distance, intermediate (80 cm), and near vision (40 cm) at least 3 weeks postoperatively (UDVA, UIVA, UNVA, respectively) tested with the Early Treatment Diabetic Retinopathy Study (ETDRS) acuity charts (intermediate and near).

All subjects fulfilled a follow-up questionnaire survey, based on the Johnson and Johnson questionnaire for visual performance after cataract surgery, which has been previously reported [12]. This self-reported questionnaire is given routinely at our center to all cataract patients who were implanted with a multifocal or an EDOF IOL at their follow-up appointment at least 3 weeks after the surgery to assess spectacle dependence, visual perception, symptoms of haloes and/or glare, and overall patient satisfaction. The answers were categorized and graded from 1 to 5. Results of visual outcomes and patients’ self-assessment questionnaires were compared between the two groups. In cases where both eyes were scheduled for surgery, the questionnaire administered 3 weeks after the second eye surgery was utilized. If only one eye was operated on, or if the surgeries were not performed consecutively, the questionnaire was completed following the unilateral surgery.

The IOL power was selected based on various calculation formulas at the surgeon’s discretion to target emmetropia or minimal myopia. The Barrett online toric calculator [13] was used in cases with corneal astigmatism as indicated by keratometry and corneal topography. Additional adjustments were taken under consideration according to the surgeon’s experience and preferences (e.g., surgical incision site, posterior corneal astigmatism, and astigmatism orientation). All procedures were done by means of phacoemulsification through a 2.4-mm clear corneal incision.

Power calculation for this study utilizing the G*Power software (version 3.1.9.6) [14] was based on the two-sided Mann-Whitney U test for the UDVA difference between the groups. To detect a difference with an effect size (f) of 0.5, based on an anticipated SD of 0.1 and mean difference of 0.05, setting the significance level (alpha) at 0.05 and the power at 0.80, the calculated total sample size necessary to achieve sufficient statistical power is 102 subjects. Continuous variables were compared using the Mann-Whitney U test, as indicated by a normality test (Shapiro-Wilk). Pearson’s χ² test or Fisher’s exact test were used, as appropriate, to compare patients’ feedback from the survey, which were expressed as proportions and assessed as categorical variables. For analysis purposes of spectacles use, the answers “Never” and “Rarely” were grouped as positive outcomes. For questions regarding the quality of vision, the answers “Good” and “Excellent” were considered as high patient satisfaction. The existence of photopic phenomena was attributed to answers graded as “Often” and “All the time.” Patient satisfaction was graded as positive if the patient would choose or probably choose the same again. Statistical analyses were performed with the Statistical Package for the Social Sciences (version 21.0; SPSS, Inc., Chicago, IL, USA). A p value <0.05 was considered statistically significant.

The study included 133 eyes of 97 patients, of them 33 eyes with retinal pathologies (24 eyes with ERM and 9 eyes with dry AMD) and 100 eyes in the control group. Their characteristics and demographics are listed in Table 1. Patients with retinal pathologies were generally older than the patients with healthy eyes (71.0 ± 5.9 vs. 65.8 ± 10.1, respectively, p = 0.012) and had a lower percentage of bilateral EDOF implantation during the study period than the control group (17.9% vs. 44.9%, respectively, p = 0.012). There were no other differences among patients’ characteristics and the implanted IOL parameters between the two groups. No IOL exchange was required in any case. No case in the retinal pathology group required any additional treatment or retina surgery during the study period.

The mean postoperative refractive spherical equivalent results were similar between the two groups. Uncorrected visual acuities (LogMAR) for all distances were significantly better in the healthy eyes group in comparison with eyes with retinal pathologies: 0.05 ± 0.09 and 0.10 ± 0.09, p = 0.011 (UDVA), 0.06 ± 0.10 and 0.16 ± 0.13, p = 0.001 (UIVA), and 0.20 ± 0.14 and 0.28 ± 0.17, p = 0.026 (UNVA), respectively (Table 2). Figure 1 displays the visual outcomes of both groups.

Ninety-one questionnaires were completed, 26 (79%) in the retinal pathology group and 65 (65%) in the control group. No statistically significant difference was found between the groups in the patients’ visual acuity perception and spectacle independence for distance, with “excellent” or “good” visual acuity reported by 92.0% in the retinal pathology group and 90.8% of the patients with healthy eyes (p > 0.999), and 88.5% versus 96.9%, respectively, reported as “never” or “rarely” using spectacles (p = 0.139). For the intermediate range, a lower rate of patients with retinal pathologies reported “excellent” or “good” vision than with healthy eyes (46.2% vs. 75.4%, respectively, p = 0.007), yet no difference was found in spectacle independence between the groups (80.0% vs. 84.6%, respectively, p = 0.753). Near vision was perceived similarly by both groups (42.3% vs. 30.8%, respectively, p = 0.294), however, fewer patients with retinal pathologies “never” or “rarely” used near spectacles than healthy eyes (26.9% vs. 52.3%, respectively, p = 0.028). In total, 38.5% in the retinal pathology group and 70.8% in the healthy eyes group reported “rarely” or “no need” spectacles for all the distances (p = 0.004). Twenty-three percent of patients in the retinal pathology group and 17% in the control healthy eyes group reported haloes and/or glare “most” or “all the time” (p = 0.556), and only 4% and 7% of patients, respectively, reported that it was functionally disturbing “most” or “all of the time” (p > 0.999). Seventy-three percent and 77% of the patients, respectively, reported that they would choose the same IOL again (p = 0.699). The complete self-assessment results are presented in Table 3.

In this study, we showed that at least one design of the EDOF IOL can be considered in patients with mild dry AMD or stable ERM without foveal distortion (no more than foveal flattening) or intraretinal fluids, who were approved by a retina specialist for cataract surgery alone.

To be suitable for an MIOL, beyond personal preferences, a patient needs to have the potential for excellent vision after the surgery. Therefore, despite the growing demand to reduce spectacle dependence after cataract surgery, due to the complexity of MIOL implantation in cases with retinal pathologies, both because of the potential vision limitations and the optical effects of these lenses, there is limited evidence for this practice [15‒18]. Given that the EDOF IOL is assumed to be a more forgiving IOL than the traditional MIOL, some patients with mild retinal pathologies, as described previously, who would not qualify for the MIOL may be considered for the EDOF IOL. It is important to note that extra caution must be taken for such patients; they should have proper expectations and should not be automatically implanted with the EDOF IOL.

While demonstrating good outcomes, visual performance in eyes with retinal pathologies did not reach the levels observed in healthy eyes. This was reflected in superior visual acuity results across all ranges and questionnaire outcomes, with an advantage noted in perceived visual acuity for intermediate vision and reduced need for near vision spectacles in the group of healthy eyes. Overall, patients in the healthy eyes group reported greater spectacles independence; 71% of the patients with healthy eyes reported “rarely” or “never” using spectacles for all distances compared with 38% of patients with retinal pathologies.

Although unaided visual acuity in the retinal pathology group in our study fell short of that of the healthy eyes group, we found that the patients with retinal pathologies achieved excellent uncorrected distance vision, with reasonable mid- and near-range uncorrected acuities with the EDOF IOL. Comparing our uncorrected visual acuity results to other studies of the EDOF IOL showed comparable results for both the healthy eyes and retinal pathology groups, with UDVA between −0.02 and 0.08, UIVA from 0.01 to 0.27, and UNVA from 0.07 to 0.27, even though they generally excluded eyes with ocular pathologies [4‒9, 19]. It is important to note that administering a questionnaire after bilateral surgery will likely yield higher satisfaction scores, especially concerning intermediate and near vision. The disparity in bilateral cases in our study between eyes with retinal pathologies (17.9%) and healthy eyes (44.9%) is disadvantageous to the pathology group. Nonetheless, despite the inherent advantage of the control group, our study demonstrates favorable outcomes with the EDOF IOL in patients with mild and stable retinal pathologies, thereby strengthening the study’s findings. In addition, while photic phenomena are a known downside of presbyopia-correcting IOLs, dysphotopsia rates were low in both the healthy and retinal pathology groups, showing no significant difference; 83% in the healthy group and 77% in the retinal pathology group reported experiencing “no” to “some” haloes and glare. Furthermore, only 7% in the healthy group and 4% in the retinal pathology group reported that these issues frequently disturbed their daily activities, with none requiring IOL exchange. These percentages of dysphotopsia, in both groups, are aligned with the range described in the literature for post-EDOF implantation [4, 8, 20]. Finally, despite disparities in visual acuity, satisfaction with the IOL remained high; 73% in the pathology group and 77% in the healthy group would choose the EDOF IOL again, showing no significant difference between the groups.

Jeon et al. [21] also reported on the clinical outcomes after implantation of an EDOF IOL (Alcon Vivity^®) in eyes with low-grade ERM. They showed similar outcomes as for eyes without ERM in UDVA (0.03 vs. 0.01, respectively) and dysphotopsia frequency (glare 28.9% vs. 26%, halo 33.3% vs. 24%, respectively). However, eyes with ERM, compared to those without ERM, exhibited lower UIVA (0.14 vs. 0.09) and UNVA (0.23 vs. 0.19) and reduced contrast sensitivity. These findings align with our study, although slight numerical discrepancies were observed across various metrics, potentially attributable to differences in patient characteristics, the type IOL, or random variability in research. Contrary to us, they did not inquire about patients' subjective perception of vision in their survey, nor did they assess dependence on glasses. Additionally, this study used the Vivity IOL, an EDOF IOL employing a non-diffractive X-WAVE^™ technology, in contrast to the Symfony IOL we examined, which is based on a diffractive Echolette design.

Several studies have examined the outcomes of EDOF IOLs in eyes with other ocular pathologies traditionally considered contraindicated for MIOLs. Ferguson et al. evaluated the EDOF IOL in eyes with mild open-angle glaucoma [22]. Their visual acuity outcomes were similar to ours, with 0.03, 0.18, and 0.31 for UDVA, UIVA, and UNVA, respectively. In the self-reported outcomes, the results also trended similarly to our study, with 92%, 50%, and 38% of participants “never” requiring glasses for distance, intermediate, and near vision, respectively. Additionally, this study, like ours, observed a high satisfaction rate with EDOF IOLs, despite ocular pathology, with 85% of participants indicating they would choose this IOL again. Another study by Mitchell et al. indicated a benefit of the EDOF IOL in eyes with early-stage glaucoma compared to monofocal lenses, yielding superior intermediate and near vision outcomes with no difference in distant visual acuity [23]. Miyajima et al. also compared the visual functions of diffractive EDOF IOLs with monofocal IOLs in eyes with mild to moderate primary open-angle glaucoma and found no significant differences in mean deviation of the visual field, corrected distance visual acuity, or contrast sensitivity between the two [24]. Similarly, post-refractive surgery patients exhibited increased satisfaction rates (73%) with an EDOF IOL implantation compared to a monofocal IOL (33%), attributed to better intermediate visual outcomes [25]. In a different study investigating the outcomes of EDOF IOLs in eyes with diverse pathologies, including past corneal refractive surgery, mild and nonprogressive maculopathy, glaucoma, amblyopia, and previous vitrectomy, a total of 85.5%–90% of patients were completely to moderately satisfied with the outcome achieved [26]. Similar to our observations, these aforementioned studies provide support for the potential role of EDOF IOLs for presbyopia correction in certain ocular conditions that may preclude or limit the patient’s suitability for MIOLs.

An additional consideration is the potential risk of progression of the retinal pathology. In these cases, the EDOF IOL has an inherent disadvantage. However, elderly patients, even if disease-free at the time of cataract surgery, are at risk of developing retinal pathologies due to their age. The annual incidence of early AMD in a population aged 60–80 years was found to be 3.4% in the Copenhagen City Eye Study [27]. A prevalence of early AMD of 11% in people older than 75 years was reported. The Blue Mountains Eye Study reported increased prevalence of ERM in the population older than 60 years with a peak prevalence of 11.6% observed in those between 70 years and 79 years [28]. Additionally, ERM was found in 16.8% of persons who had undergone cataract surgery [28]. So elderly patients, even if free of retinal pathology during the cataract surgery, have a risk of developing it later in life. However, most patients with AMD will maintain a low disease activity, as demonstrated in the AREDS study, which showed that among patients with early AMD, the risk of progression to category 4 AMD over a 5-year period was 1.3% [29]. In the case of ERM, the majority of patients are also unlikely to progress, as supported by the findings from the Blue Mountains Eye Study, which indicated that ERM remained in more than 70% of patients over a 5-year follow-up period [30]. Nevertheless, the increased risk in cases of stable AMD and ERM requires a risk management approach, with meticulous selection of candidates for an EDOF IOL in these cases. Due to the increased risk in cases where retinal pathology already exists, it is especially important to communicate the advantages and disadvantages well to the patients to obtain an informed decision to their discretion.

Our study is limited by its retrospective nature. As a consequence, the retinal pathology group was relatively small and not heterogenic. Additionally, binocular visual acuities and objective contrast sensitivity were not measured. Another limitation is the lack of long-term follow-up data, which restricts our ability to evaluate the sustainability of visual outcomes, particularly in patients with retinal pathologies who may be at risk of disease progression. Nevertheless, this study's strength lies in analyzing a real-world population, enabling valid comparisons between groups due to the consistent setting.

In conclusion, we found that the EDOF IOL could be cautiously considered for some patients with mild stable dry AMD and ERM, who are traditionally excluded from MIOLs, after proper management of patient expectations, offering excellent uncorrected visual outcomes for distance range with reasonable results for intermediate and near vision, significantly minimizing the need for spectacles. Although results were inferior to the group with healthy eyes, patients’ satisfaction in both groups was high and similar. The findings of this study are encouraging, but further comparative and prospective studies with longer follow-up and larger sample size are desired.

The study adhered to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of the Meir Medical Center, Kfar Saba, Israel (No. 0046-12-MMC [Meir Medical Center]). Data were collected retrospectively in a case-control study design. As this study was based on retrospective data available in patients’ medical records, it was exempt from obtaining an informed consent from its participants by the Institutional Review Board of the Meir Medical Center, Kfar Saba, Israel.

Ehud I. Assia: Hanita Lenses – consultant; Biotechnology General (Israel) Ltd – consultant; Vision Care Technologies – research fee, options holder; APX Ophthalmology – founder, CMO; IOPtima – shareholder; VisiDome – founder, CMO; CorNeat – shareholder. Guy Kleinmann: Hanita Lenses – consultant; Johnson and Johnson vision – consultant, CorNeat – consultant. No other author has a financial or proprietary interest in any material or method mentioned.

This study was not supported by any sponsor or funder.

Olga Reitblat and Guy Kleinmann: conception or design of the work, data acquisition, analysis and interpretation of data for the work, drafting and revising the work, and final approval of the version to be published; David A. Velleman: data acquisition, analysis and interpretation of data for the work, drafting and revising the work, and final approval of the version to be published; Adi Levy: data acquisition, analysis and interpretation of data for the work, revising the work, and final approval of the version to be published; and Ehud I. Assia: conception or design of the work, analysis and interpretation of data for the work, revising the work, and final approval of the version to be published. Olga Reitblat, David A. Velleman, Adi Levy, Ehud I. Assia, and Guy Kleinmann agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

The data that support the findings of this study are not publicly available due to the restrictions of the Institutional Research Ethics Board approval of this study but are available from the corresponding author (O.R.) upon personal request.