As the diversity of premium intraocular lenses (IOL) increases, additional factors should be considered for selection based on patient characteristics. Among premium IOL diversifications, the most notable development is the extended depth-of-focus (EDoF) IOL. These IOLs are gaining popularity rapidly, as they produce less dysphotopsia and better contrast sensitivity compared with diffractive IOLs [1-5]. Additionally, patients with mild retinal diseases might benefit from the greater tolerance among EDoF IOLs [6].

One retinal disease that may be a good candidate for EDoF IOL is epiretinal membrane (ERM) [6]. ERM is one of the most common retinal diseases [7], with various ranges of visual deterioration [8]. Although advanced ERM is a vision-threatening disease, early-stage ERM has little effect on visual quality and typically is reversible with surgical correction. EDoF IOLs showed favorable outcomes in eyes with mild ERM [6], in contrast with diffractive IOLs, which showed poor results [9,10].

In the present study, we evaluate the clinical outcomes of visual acuity and visual quality for AcrySof^® IQ Vivity^TM (Alcon Laboratories) IOLs in patients with various ERM stages (up to stage 3) as detected by OPD-scan and contrast sensitivity.

We performed a retrospective chart review of eyes that underwent phacoemulsification and lens implantation with a Vivity IOL from May 15, 2021, to November 31, 2022. Patients were grouped according to ERM stage as on spectral domain optical coherence tomography (Spectralis SD-OCT; Heidelberg Engineering) [11]: stage 1, mild and thin ERM not disrupting the foveal depression; stage 2, widening of the outer nuclear layer and loss of foveal depression; stage 3, continuous ectopic inner foveal layers (EIFL) crossing the entire foveal area; and stage 4, disrupted retinal layers (Fig. 1). Cataract grade was classified according to previous recommendation by Mandelblum et al [12].

Fig. 1. Representative spectral-domain optical coherence tomography for stage 1 (A), stage 2 (B), and stage 3 (C) epiretinal membrane.

Eyes with retinal disease other than ERM, preoperative corrected distant visual acuity (CDVA) less than 20/40, previous corneal or vitreoretinal surgery, intraoperative capsular damage, or any postoperative complication were excluded from analysis. The Institutional Review Board (IRB) of Keye Eye Center approved the study (IRB number: P12362204-002) and waived the requirement for informed consent because of the study’s retrospective nature. The study protocol adhered to the tenets of the Declaration of Helsinki.

Surgical technique

The IOL power was selected to target emmetropia by choosing the first negative power IOL using the Kane formula with data generated from the IOL Master 700 (Carl Zeiss Meditec). Toric IOL was implanted in eyes with corneal astigmatism exceeding 0.50 diopters (D). Cataract surgery was performed by experienced surgeon (S.J) after applying topical anesthesia using preservative-free lidocaine. Continuous curvilinear capsulorhexis was performed using a femtosecond laser (LENSAR, Inc.) with a 5.2-mm diameter to minimize IOL misalignment. Then, a 2.2-mm incision was made on the temporal cornea using a diamond blade. Cataract surgery was performed using a Centurion^® (Alcon Laboratories). We performed neodymium-doped yttrium aluminum garnet capsulotomy for clinically significant posterior capsule opacification.

We recommend ERM removal for ERM stage 3 and worse. Eyes with metamorphopsia or outer retinal damage, including stage 4 ERM, are contraindications for any multifocal IOL in our institution. The presence of metamorphopsia was evaluated with the Amsler grid. For ERM, a single experienced vitreoretinal surgeon (S.J) performed all operations using a 25-gauge standard sutureless pars plana vitrectomy system (Alcon Laboratories) and the NGENUITY 3D Visualization System (Alcon Laboratories). Subtenon anesthesia using lidocaine was applied before surgery. After core vitrectomy, the posterior hyaloid membrane was detached using the vitrectomy probe in suction mode around the optic nerve disc, if needed, and peripheral vitreous shaving was conducted. The ERM was peeled away using intraocular forceps coated with triamcinolone (MaQaid; Hanmi Pharmaceutical Co Ltd.). The internal limiting membrane was removed, either concurrently or after ERM removal, within a fovea-centered circular area of 2-3 optic disc diameters using 0.5% indocyanine green dye (Dongindang Inc.). After a close inspection of the periphery, trocars were removed. No intraocular tamponade or periocular injection of antibiotics or steroids was used.

Outcome measurements

Monocular uncorrected distance, intermediate and near visual acuity (UDVA, UIVA, and UNVA, respectively), and CDVA were assessed at postoperative months 1, 2, 6, 12, and 24. Visual acuities were measured using the decimal system and converted into logarithm of the minimum angle of resolution (logMAR) for statistical analyses. Near and intermediate visual acuities were measured using the Sloan ETDRS Format Near Vision Chart 3 with 100% contrast under photopic conditions (167 candelas/m2) at 40 and 66 cm. Refractive error was measured with an autorefractor (ARK-1; NIDEK Co., Ltd.).

Contrast sensitivity using the CGT-2000 instrument (Takagi Seiko) was measured at postoperative month 6 or 12. The area under the logarithm of contrast sensitivity function (AULCSF) was compared between groups under mesopic and photopic conditions. The Strehl ratio of the point spread function from the postoperative root mean square (RMS) of the total ocular wave aberration Z (1 ≤ n ≤ 8) was assessed for a pupil diameter of 5.0 mm with optical path difference scan (OPD-scan III, NIDEK Co. Ltd.).

Statistical analysis

IBM SPSS ver. 15.0 (IBM Corp.) was used for statistical analysis. Unless otherwise specified, descriptive data were recorded as mean ± standard deviation. The Shapiro-Wilk test assessed the normality of continuous variables using analysis of variance to compare three or more data points. The least significant difference (LSD) test was used for post-hoc analysis. The chi-square test was used to compare categorical variables between groups. Comparisons of nonpaired variables were performed with the Mann-Whitney test. All p-values are two-sided, and significance was set at < 0.05.

We found 289 eyes that met our inclusion criteria. Fig. 2 shows the standard graphs for the clinical outcomes of enrolled patients. Among the 289 eyes, 228 (78.9%) had no ERM, 29 (10.0%) had stage 1 ERM, 20 (6.9%) had stage 2 ERM, and 12 (4.2%) had stage 3 ERM. The mean patient age was 60.40 ± 5.57, 62.86 ± 5.60, 62.72 ± 4.76, and 64.17 ± 3.83 years for no ERM, stage 1, stage 2, and stage 3 ERM, respectively (p = 0.008). There was no difference between stage groups in sex, laterality, preoperative refractive error, UDVA, axial length, anterior chamber depth, lens thickness, horizontal corneal diameter, or pupil size (p = 0.598, 0.626, 0.241, 0.167, 0.678, 0.506, 0.243, 0.644, and 0.116, respectively). Preoperative cataract grade showed significant difference among groups: 2.18 ± 0.47, 2.52 ± 0.63, 2.55 ± 0.69, and 3.00 ± 0.85 for no ERM, stage 1, stage 2, and stage 3 ERM, respectively (p < 0.001). Steep K was 44.12 ± 1.52, 44.77 ± 1.74, 43.91 ± 1.87, and 45.18 ± 1.70 for no ERM, stage 1, stage 2, and stage 3 ERM, respectively (p = 0.035). Flat K was 43.54 ± 1.46 for no ERM, 44.12 ± 1.65 for stage 1, 43.36 ± 1.80 for stage 2, and 44.56 ± 1.59 for stage 3 ERM (p = 0.045).

Fig. 2. Standard graphs for clinical outcomes of enrolled patients. postop = postoperative; UDVA = uncorrected distance visual acuity; CDVA = corrected distance visual acuity; D = diopters.

There was no difference in postoperative refractive error among groups (Table 1; -0.20 ± 0.26, -0.17 ± 0.30, -0.11 ± 0.32, and -0.07 ± 0.30 for no ERM, stage 1, stage 2, and stage 3 ERM groups, respectively; p = 0.191). Fig. 3 shows postoperative visual acuities according to group. There were no differences between groups for UDVA, UIVA, UNVA, and CDVA according to ERM stage. Postoperative UDVA was 0.02 ± 0.06, 0.02 ± 0.05, 0.02 ± 0.04, and 0.04 ± 0.07 for no ERM, stage 1, stage 2, and stage 3 ERM, respectively; p = 0.639). Postoperative UIVA was 0.12 ± 0.20, 0.15 ± 0.11, 0.15 ± 0.10, and 0.12 ± 0.13 for no ERM, stage 1, stage 2, and stage 3 ERM, respectively; p = 0.871). Postoperative UNVA was 0.21 ± 0.12, 0.20 ± 0.09, 0.22 ± 0.11, and 0.21 ± 0.08 for no ERM, stage 1, stage 2, and stage 3 ERM, respectively; p = 0.963). Postoperative CDVA was 0.00 ± 0.02, 0.01 ± 0.02, 0.02 ± 0.06, and 0.03 ± 0.07 for no ERM, stage 1, stage 2, and stage 3 ERM, respectively; p = 0.051).

Fig. 3. Bar graph showing visual outcomes after Vivity IOL implantation according to ERM stage. UDVA = uncorrected distance visual acuity; UIVA = uncorrected intermediate visual acuity; UNVA = uncorrected near visual acuity; CDVA = corrected distance visual acuity; ERM = epiretinal membrane.

Table 1

Demographic and ocular data of the enrolled eyes (n = 289)

Variable	No ERM (n = 228)	Stage 1 (n = 29)	Stage 2 (n = 20)	Stage 3 (n = 12) p-value
Age (years)	60.40 ± 5.57	62.86 ± 5.60	62.72 ± 4.76	64.17 ± 3.83	0.008
Sex, male	76 (33.3)	7 (24.1)	8 (40.0)	5 (41.7)	0.598*
Laterality, OD	114 (50.0)	14 (48.3)	13 (65.0)	6 (50.0)	0.626*
Cataract grading	2.18 ± 0.47	2.52 ± 0.63	2.55 ± 0.69	3.00 ± 0.85	< 0.001
Preoperative RE (D)	1.14 ± 1.55	1.36 ± 1.59	1.02 ± 1.97	1.08 ± 0.25	0.241
Postoperative RE (D)	-0.20 ± 0.26	-0.17 ± 0.30	-0.11 ± 0.32	-0.07 ± 0.30	0.191
Preoperative UDVA	0.41 ± 0.26	0.48 ± 0.27	0.43 ± 0.28	0.56 ± 0.27	0.167
AL (mm)	23.54 ± 0.85	23.36 ± 0.69	23.63 ± 0.95	23.38 ±1.04	0.678
ACD (mm)	3.08 ± 0.34	3.18 ± 0.34	3.09 ± 0.35	3.11 ± 0.36	0.506
LT (mm)	4.52 ± 0.29	4.50 ± 0.33	4.64 ± 0.21	4.65 ± 0.26	0.243
Steep K (D)	44.12 ± 1.52	44.77 ± 1.74	43.91 ± 1.87	45.18 ± 1.70	0.035
Flat K (D)	43.54 ± 1.46	44.12 ± 1.65	43.36 ± 1.80	44.56 ± 1.59	0.045
HCD (mm)	11.87 ± 0.41	11.88 ± 0.38	11.90 ± 0.36	11.71 ± 0.49	0.644
Pupil size (mm)	3.81 ± 0.70	3.62 ± 0.59	3.72 ± 0.64	3.36 ± 0.56	0.116

Values are mean ± standard deviation or number (%).

ERM = epiretinal membrane; OD = oculus dexter; RE = refractive error; D = diopters; UDVA = uncorrected distance visual acuity; AL = axial length; ACD = anterior chamber depth; LT = lens thickness; K = keratometry; HCD = horizontal corneal diameter.

*Chi-square test.

Table 2 shows postoperative visual quality according to ERM stage. There was no significant difference in the Strehl ratio (0.03 ± 0.01, 0.03 ± 0.01, 0.02 ± 0.01, and 0.03 ± 0.02 for no ERM, stage 1, stage 2, and stage 3 ERM, respectively; p = 0.208), area ratio at 4 m m (40.76 ± 9.47, 42.70 ± 8.46, 38.85 ± 5.80, and 37.75 ± 9.06 for no ERM, stage 1, stage 2, and stage 3 ERM group; p = 0.434), or area ratio at 5 mm (39.15 ± 8.27, 40.29 ± 36.05, 36.05 ± 5.07, and 35.40 ± 14.11 for no ERM, stage 1, stage 2, and stage 3 ERM group; p = 0.511). Ocular aberrations showed no difference according to ERM stage (p = 0.311 for total aberration, p = 0.857 for high-order aberration, p = 0.816 for coma, p = 0.599 for trefoil, p = 0.577 for spherical aberration).

Table 2

Postoperative visual quality according to ERM stage (n = 289)

Variable	No ERM (n = 228)	Stage 1 (n = 29)	Stage 2 (n = 20)	Stage 3 (n = 12)	p-value
Strehl ratio	0.03 ± 0.01	0.03 ± 0.01	0.02 ±0.01	0.03 ± 0.02	0.208
Area ratio, 4 mm	40.76 ± 9.47	42.70 ± 8.46	38.85 ± 5.80	37.75 ± 9.06	0.434
Area ratio, 5 mm	39.15 ± 8.27	40.29 ± 36.05	36.05 ± 5.07	35.40 ± 14.11	0.511
Ocular aberration
Total aberration	0.84 ± 0.29	0.77 ± 0.18	0.78 ± 0.22	0.98 ± 0.79	0.311
High order aberration	0.41 ± 0.15	0.38 ± 0.11	0.41 ± 0.11	0.40 ± 0.17	0.857
Coma	0.15 ± 0.10	0.13 ± 0.05	0.15 ± 0.08	0.16 ± 0.17	0.816
Trefoil	0.28 ± 0.17	0.25 ± 0.10	0.23 ± 0.13	0.31 ± 0.24	0.599
Spherical aberration	0.14 ± 0.08	0.13 ± 0.07	0.16 ± 0.06	0.13 ± 0.03	0.577
Contrast sensitivity
AULCSF, day*	1.48 ± 0.21	1.41 ± 0.18	1.33 ± 0.17	1.31 ± 0.19	0.036
AULCSF, night†	1.21 ± 0.21	1.22 ± 0.12	1.02 ± 0.20	1.08 ± 0.10	0.027

Values are presented as mean ± standard deviation. Mann-Whitney test was used for the comparison.

ERM = epiretinal membrane; AULCSF = area under the logarithm of contrast sensitivity function; LSD = least significant difference.

*p = 0.285 for no ERM vs. stage 1 ERM, p = 0.060 for no ERM vs. stage 2 ERM, p = 0.028 for no ERM vs. stage 3 ERM, p = 0.424 for stage 1 vs. 2 ERM, p = 0.288 for stage 1 vs. 3 ERM, and p = 0.810 for stage 2 vs. 3 ERM (post hoc analysis using the LSD test); †p = 0.836 for no ERM vs. Stage 1 ERM, p = 0.010 for no ERM vs. stage 2 ERM, p = 0.086 for no ERM vs. stage 3 ERM, p = 0.029 for stage 1 vs. 2 ERM, p = 0.132 for stage 1 vs. 3 ERM, and p = 0.529 for stage 2 vs. 3 ERM (post hoc analysis using the LSD test).

The contrast sensitivity represented by AULCSF showed significant differences in both day (p = 0.036) and night conditions (p = 0.027). The AULCSF for day condition was 1.48 ± 0.21 in patients with no ERM, 1.41 ± 0.18 in stage 1, 1.33 ± 0.17 in stage 2, and 1.31 ± 0.19 in stage 3. Post-hoc analysis using the LSD test showed a significant difference between patients with no ERM vs. stage 3 ERM (p = 0.285 for no ERM vs. stage 1 ERM, p = 0.060 for no ERM vs. stage 2 ERM, p = 0.028 for no ERM vs. stage 3 ERM, p = 0.424 for stage 1 vs. 2 ERM, p = 0.288 for stage 1 vs. 3 ERM, and p = 0.810 for stage 2 vs. 3 ERM). AULCSF at night was 1.21 ± 0.21 in patients with no ERM, 1.22 ± 0.12 in stage 1 ERM, 1.02 ± 0.20 in stage 2, and 1.08 ± 0.10 in stage 3. Post-hoc analysis using the LSD test showed a significant difference between patients with no ERM vs. stage 2 ERM and between patients with stage 1 ERM vs. stage 2 ERM (p = 0.836 for no ERM vs. stage 1 ERM, p = 0.010 for no ERM vs. stage 2 ERM, p = 0.086 for no ERM vs. stage 3 ERM, p = 0.029 for stage 1 vs. 2 ERM, p = 0.132 for stage 1 vs. 3 ERM, and p = 0.529 for stage 2 vs. 3 ERM).

Fig. 4 shows retinal images of a 63-year-old female who underwent bilateral Vivity implantation. Before surgery, she had vitreomacular traction on both retinas with stage 1 ERM in the right eye. We implanted a Vivity IOL because she had a high likelihood of ERM progression due to an abnormal vitreoretinal interface [13]. Postoperatively, ERM progressed to stage 3 in the right eye, but the left eye showed no change. At postoperative 12 months, her logMAR UDVA was 0.0 for both eyes; UIVA was 0.1 and 0.0 for the right and left eyes, respectively; and UNVA was 0.3 and 0.1 for the right and left eyes. OPD-scan showed worse visual quality in the right eye than the left. Despite the difference in objective visual function in the eyes, the patient does not report disturbance to her daily life. She is under observation for timely removal of ERM.

Fig. 4. Retinal imaging of a 63-year-old female who underwent bilateral Vivity implantation (A; OD, B; OS). Preoperative spectral domain optical coherence tomography images showed vitreomacular traction on both retinas and stage 1 ERM in the right eye (C; OD, D; OS). At postoperative 6 months, ERM progressed to stage 2 in the right eye, while stage 1 ERM developed after posterior vitreous detachment in the left eye (E; OD, F; OS). At postoperative 12 months, ERM progressed to stage 3 in the right eye, but the left eye showed no change (G; OD, H; OS). Optical path difference (OPD) scan at postoperative one year showed better visual function in the left than in the right eye. OD = oculus dexter; OS = oculus sinister; ERM = epiretinal membrane.

Among 12 eyes with stage 3 ERM, three underwent concurrent phaco-vitrectomy for ERM removal (Table 3). There was no significant difference in UDVA, UIVA, UNVA, CDVA, or AULCSF at day or night (p = 0.282, 0.800, 0.864, 0.786, 0.857 and 0.429, respectively) between eyes with stage 3 ERM based on operation performance.

Table 3

Postoperative visual outcomes of stage 3 ERM according to ERM removal (n = 12)

Variable	No ERM Removal (n = 9)	ERM Removal (n = 3)	p-value
Visual acuity
UDVA	0.06 ± 0.07	0.00 ± 0.00	0.282
UIVA	0.13 ± 0.15	0.10 ± 0.14	0.800
UNVA	0.21 ± 0.08	0.20 ± 0.06	0.864
CDVA	0.04 ± 0.09	0.00 ± 0.00	0.786
Contrast sensitivity
AULCSF, day	1.27 ± 0.21	1.42 ± 0.12	0.857
AULCSF, night	1.08 ± 0.11	1.10 ± 0.05	0.429

Values are presented as mean ± standard deviation. Mann-Whitney test was used for the comparison.

ERM = epiretinal membrane; UDVA = uncorrected distant visual acuity; UIVA = uncorrected intermediate visual acuity; UNVA = uncorrected near visual acuity; CDVA = corrected visual acuity; AULCSF = area under the logarithm of contrast sensitivity function.

Fig. 5 shows retinal images of a patient who underwent bilateral Vivity implantation and pars plana vitrectomy with membrane peeling on the right eye. She had stage 3 ERM (Fig. 5A, C), but she did not experience metamorphopsia. We implanted Vivity in both eyes and performed concurrent vitrectomy with membrane removal in her left eye because she desired intermediate vision, and the ERM showed an intact outer retinal structure on SD-OCT. At postoperative 12 months, the eyes showed the same visual acuities (logMAR UDVA 0.0, UIVA 0.1, and UNVA 0.2 for each eye). Contrast sensitivity was worse in the right eye than the left eye. Nevertheless, the patient preferred the visual function of her right eye, presumptively because of the removal of pre-existing vitreous opacity.

Fig. 5. Retinal imaging of a 66-year-old female who underwent bilateral Vivity implantation and pars plana vitrectomy with membrane removal in the right eye. Preoperative fundus photography (A) and spectral domain optical coherence tomography images (C) showed stage 3 epiretinal membrane in her right eye. Postoperative images (B, D) at 12 months showed ectopic inner retinal layer loss. Her left eye had no retinal abnormality (E, F). Contrast sensitivity at postoperative 12 months (G) showed better visual function of the left eye than the right eye. Triangle line = left eye in day conditions; diamond line = right eye in day conditions; circle line = left eye in night conditions; square line = right eye in night conditions.

Retinal disease has long been a contraindication for multifocal IOL implantation [14]. However, as new IOLs with greater tolerance have been developed, a new discussion on the indications and contraindications of each specific IOL is due [15]. This is true particularly for ERM, which involves only the inner retina in the early disease course and is reversible with timely membrane removal.

A series of studies on multifocal IOL and ERM found very different functional outcomes between diffractive and EDoF IOLs in eyes with ERM [6,9,10]. In addition to published data, many surgeons agree that, after successful EDoF IOL implantation, few patients complain of the unbearable visual symptoms often reported after successful diffractive IOL implantation. The only drawback reported is the need for reading glasses, which generally is not problematic for elderly patients with significant cataracts preoperatively. Therefore, EDoF IOL would be the first choice for patients with lower visual expectation but greater risk of ocular comorbidity.

We speculate that the superior function of EDoF IOLs on patients with ERM is due not only to the relatively low added power, but also to the optical design. In eyes with ERM, the membrane is not the sole obstacle preventing light from reaching photoreceptor cells. Most patients with ERM exhibit various degrees of vitreous opacity that could significantly impact visual quality in certain circumstances. Light is divided into multiple fractions by a diffractive IOL according to specific diffractive kino-forms present throughout the optic area [16,17]. Each fraction of diffracted light will encounter different patterns of vitreous opacity and fibrous membranes before they reach the photoreceptor cells. In contrast, EDoF IOL has a smaller area that elongates focus by changing the spherical aberration at the central 2.2-mm zone. Therefore, the light encounters fewer obstacles from vitreous opacity and fibrous membranes.

The optical design of smooth curves within a restricted area rather than concentric steps throughout the optic area causes less discomfort but provides low additional visual power [18]. Accordingly, EDoF IOL might not enhance intermediate and near vision at an advanced ERM stage, limiting the effects of premium IOL. Therefore, the benefits of advanced ERM for intermediate and near visual function of the EDoF IOL for patients is time-sensitive.

This study found that eyes with stage 3 ERM had similar visual acuity to eyes with less severe disease. However, the contrast sensitivity during the day, represented by AULCSF in such patients, was significantly worse than that in patients with no ERM. This suggests that patients with advanced ERM might experience worse visual function despite favorable visual acuities. Additionally, such favorable acuity for stage 3 ERM is possible only with timely surgical removal.

Though this is the first report of visual outcomes after Vivity implantation in eyes with stage 3 ERM, there are several limitations. First, we included a small number of patients. Second, data from only two surgeons were included and might be confounding. Further studies with a large population are required to confirm our preliminary findings.

This study was supported by investigator initiated studies funded by Alcon and grants from Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2021R1I1A1A01056094). Additionally, the authors wish to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2022.

The authors have no conflicting relationships.

Conception (S.J.); Design (K.M., S.J.); Data acquisition (K.M., Y.S.Y., S.J.); Analysis (K.M., S.J.); Interpretation (K.M., Y.S.Y., S.J.); Writing (K.M., Y.S.Y., S.J.); Review (K.M., Y.S.Y., S.J.); Final approval of the article (All authors)