Comparison of binocular visual quality in six treatment protocols for bilateral cataract surgery with presbyopia correction: a prospective two-center single-blinded cohort study

Abstract

Objective

To compare the postoperative binocular visual quality in six treatment protocols for bilateral age-related cataract surgery with presbyopia correction for clinical decisions.

Materials and methods

In this prospective two-center single-blinded cohort study, participants from North or South China who underwent bilateral phacoemulsification and intraocular lens implantation were divided into six protocols: monovision, diffractive bifocal, mixed, refractive bifocal, trifocal, and micro-monovision extended range of vision (EROV). Binocular visual quality was evaluated at 3 months postoperatively, including binocular uncorrected full-range visual acuity, binocular defocus curves (depth of focus [DoF] and area under the curve [AUC]), binocular visual function (fusion function and stereopsis), binocular subjective spectacle independence rates, visual analog scale (VAS) of overall satisfaction, 25-item visual function questionnaire (VFQ-25), and binocular dysphotopsia symptoms.

Results

Of the 300 enrolled patients, 272 (90.7%; 544 eyes) were analyzed. The trifocal protocol showed excellent binocular full-range visual acuity and the best performance for most DoFs and AUCs. The monovision protocol presented the worst binocular visual quality in most perspectives, especially in convergence, distance, and near stereopsis (p < 0.001). The full-range subjective spectacle independence rates were sorted from highest to lowest as follows: trifocal (84.8%), refractive bifocal (80.9%), EROV (80.0%), mixed (73.3%), diffractive bifocal (65.2%), and monovision (32.6%) protocols, with no statistically significant differences between the former five protocols (p > 0.05). The EROV protocol achieved the highest VAS and VFQ-25 scores. The incidence of postoperative binocular dysphotopsia symptoms was comparable in all protocols.

Conclusions

The trifocal protocol showed the best performance, and the monovision protocol presented the worst performance in most perspectives of binocular visual quality for presbyopia correction. The refractive bifocal, mixed, or EROV protocols can provide an approximate performance as a trifocal protocol. Ophthalmologists can customize therapies using different protocols.

Keywords:

• Presbyopia correction
• refractive cataract surgery
• binocular visual quality
• depth of focus
• the area under the curve

Introduction

Vision impairment might increase the risk of falls and reduce the quality of life in older adults [1]. It is expected that the global population aged ≥ 60 years will grow from 1.1 billion in 2022 to 1.4 billion in 2030 [2]. The prevalence rates of age-related cataract and presbyopia will increase gradually with the aging population. Globally, cataract is the leading cause of blindness, affecting 15.2 million individuals, and the second leading cause of moderate to severe vision impairment, with 78.8 million cases in people aged ≥ 50 years old in 2020 [3]. There are 1.8 billion adults with near vision impairment due to presbyopia in 2015. The number is projected to increase to 2.1 billion in 2030 [4,5]. In the era of refractive cataract surgery, an increasing number of ophthalmologists have begun to focus on correcting presbyopia and pursuing high visual quality.

There are multiple treatment protocols for presbyopia correction in bilateral cataract surgery with intraocular lens (IOLs) implantation [3,4,6–11]. Surgeons bear the burden of obtaining precise interventions to satisfy each patient. To provide references to assist surgeons in personalizing treatments, we compared concurrently six common treatment protocols of bilateral age-related cataract surgery for presbyopia correction in this two-center cohort study in China, including monofocal, multifocal (bifocal or trifocal), and extended range of vision (EROV) IOLs, involving the design of monovision or mixed approach [12]. Patients pay more attention to binocular visual quality of protocol rather than monocular visual quality of IOL. Therefore, we evaluated binocular visual quality from different perspectives, including binocular full-range visual acuity, binocular defocus curves (depth of focus and area under the curve), binocular visual function (fusion function and stereopsis), binocular subjective spectacle independence rates, subjective questionnaires, and binocular dysphotopsia symptoms.

Materials and methods

Study design

This prospective, two-center, single-blinded cohort study was conducted under real-world conditions in accordance with the principles of the Helsinki Declaration. Ethical approvals (IRB00006761-M2019414 [477-01] [477-02] and Ethic-KY-QXQ-2020-01) were granted by the ethical committees of Peking University Third Hospital and People’s Hospital of Guangxi Zhuang Autonomous Region respectively. Registration was conducted at clinicaltrials.gov (NCT04265846) prior to the start of the study. The groupings were kept hidden from the data collectors and the outcome measure assessors. This study was managed by the same quality control supervisor at both centers.

Participants

Participants with bilateral age-related cataract were enrolled at Peking University Third Hospital and People’s Hospital of Guangxi Zhuang Autonomous Region in China between November 2019 and May 2021. Informed consent was obtained from all participants. The inclusion criteria are outlined below: ages 55–75 years old, preoperative Ocular axial length 22–26 mm, angle kappa distance <0.5 mm, cornea spherical aberration (pupil 4 mm) <0.3 μm, pupil diameter 3.0–5.5 mm in a dark room and expected postoperative astigmatism ≤1.00 diopter (D). Participants with a history of ocular trauma or surgery, pupillary abnormalities, evident strabismus, and ocular or systemic conditions known to affect visual acuity, except cataracts, were excluded. All patients underwent comprehensive ophthalmologic examination before surgery, including visual acuity, intraocular pressure, slit lamp microscopy examination, fundus examination, macular optical coherence tomography, B-mode ultrasonography, dry eye examination and ocular biometry measurements (Zeiss IOL Master 700 [Carl Zeiss, Jena, Germany] and Oculus Pentacam Corneal Topography [Oculus Optikgerate GmbH, Wetzlar, Germany]). The dominant eye was measured by the hole-in-the-card test [13].

Groupings

Participants were grouped into six protocols based on their personal habits pertaining to the use of the eyes in daily life or occupational settings, economic capacity, as well as their specific demands and preferences. Protocol 1, monovision protocol: monofocal IOL implantation bilaterally with 0 D of target refraction for the dominant eye and −2.00 D of target refraction for the nondominant eye; Protocol 2, diffractive bifocal protocol: bifocal IOL designed mainly by diffraction with the +3.00 D near additional power implantation bilaterally targeting emmetropia; Protocol 3, mixed protocol: bifocal IOL designed mainly by diffraction with +3.00 D and +2.50 D near additional power implantation bilaterally respectively with 0 D of target refraction; Protocol 4, refractive bifocal protocol, bifocal IOL designed mainly by refraction implantation bilaterally with 0 D of target refraction; Protocol 5, trifocal protocol: trifocal IOL implantation bilaterally targeting emmetropia; Protocol 6, micro-monovision EROV protocol (hereafter ‘EROV protocol’): EROV IOL implantation bilaterally with 0 D of target refraction for the dominant eye and −0.50 D of target refraction for the nondominant eye. The design scheme for these six protocols is presented in Supplemental Table S1. The Barrett Universal II Formula was used to calculate IOL power.

Surgical procedure

Experienced cataract surgeons performed bilateral phacoemulsification (Centurion, Alcon Laboratories, Inc., USA) with a 2.2 mm wide sutureless clear corneal incision at the 9–10 o’clock position and a 5.0–5.5 mm diameter of anterior continuous curvilinear capsulorhexis, combined with IOL implantation in the capsular bag. The time interval between surgeries of the two eyes ranged from one day to one month. Postoperatively, Tobramycin and Dexamethasone (s.a. ALCON-COUVREUR n.v.Belgium) eye drops were topically administered four times a day for 2 weeks.

Clinical outcome measures

At 3 months postoperatively, the following clinical outcomes were evaluated: (1) Binocular uncorrected full-range visual acuity, including uncorrected distance visual acuity (UDVA, 5 m), uncorrected intermediate visual acuity (UIVA, 80 cm or 60 cm), and uncorrected near visual acuity (UNVA, 40 cm) at the logarithm of the minimum angle of resolution [LogMAR], monocular corrected distance visual acuity and monocular absolute refractive prediction error (the absolute difference between the measured postoperatively and predicted preoperative refractive spherical equivalent) were evaluated under photopic (>85 cd/m²) conditions. (2) Binocular uncorrected defocus curves were evaluated by adding plus lenses in 0.5 D steps from +2.0 D to −4.0 D at 5 m under photopic (>85 cd/m²) condition. The binocular depth of focus (DoF) was calculated by the defocus range at cutoffs of 0.1, 0.2, and 0.3 LogMAR respectively (Supplemental Figure S1). The area under the curve (AUC) (LogMAR/m) over 0.3 LogMAR was calculated with the trapezoidal method [14] along the full region from +2.0 D to −4.0 D (full area under the curve, fAUC), distance region from +2.0 D to −0.5 D (distance area under the curve, dAUC), intermediate region from −0.5 D to −2.0 D (intermediate area under the curve, iAUC), and near region from −2.0 D to −4.0 D (near area under the curve, nAUC) (Supplemental Figure S2). (3) Binocular visual function was evaluated, including fusion function, distance stereopsis (Digital Synoptophore, TSJ-IV A, Changchun, China), and near (40 cm) stereopsis (Stereoacuity Test Chart, Yan Shao-ming, China). We calculated the proportion of patients with macular foveal stereopsis (≤60 arcsec″), macular stereopsis (80–200″), peripheral stereopsis (400–800″), and stereo blindness (>800″) at distance and near, respectively. (4) Binocular subjective spectacle independence rates were evaluated at distant (walking or driving), intermediate (reading a newspaper or using a desktop computer), near (reading a book or using a cell phone), and full-range (the activities mentioned above). (5) Subjective questionnaires were evaluated. The visual analog scale (VAS) of overall satisfaction was measured using a 0–10 rating scale representing the lowest satisfaction [0] or the highest satisfaction [10] (Supplemental Figure S3). The 25-item Visual Function Questionnaire (VFQ-25) was issued by the National Eye Institute (NEI) [15]. (6) Safety outcomes were evaluated, which included intraoperative or postoperative complications, and postoperative binocular dysphotopsia symptoms (glare, halos, and starburst). The latter refers to the grade of severity (none, a little, mild, moderate, and severe) of dysphotopsia related about the influence on daily life. (Supplemental Figure S4).

Sample size calculation

We used PASS 15.0 to perform sample-size calculation according to UDVA in previous literatures (0.06 ± 0.16 [16], −0.02 ± 0.10 [17], 0.00 ± 0.12 [17], −0.02 ± 0.12 [18], −0.10 ± 0.10 [19], −0.04 ± 0.10 [20] in the monofocal, monovision, diffractive bifocal, mixed, refractive bifocal, trifocal and EROV protocols respectively). For a = 0.05 and b = 0.9, the required sample size was 50 participants in each protocol, including a 30% dropout. There are 6 groups in this study, thus a total of 300 patients was planned to be enrolled.

Statistical analysis

We used SPSS 22.0 statistical software (IBM Corp., Armonk, NY) to perform the statistical analyses. Continuous variables are presented as mean ± standard deviation (SD) or median (lower quartile, upper quartile). For multiple-group and pairwise comparisons, the chi-square test or Fisher’s exact probability method was used for binary variables, and analysis of variance (ANOVA) or Kruskal–Wallis nonparametric tests were applied for continuous and grade data. Statistical significance was set at p value < 0.05. All p values were adjusted according to the pairwise comparison procedure using the SPSS software.

Results

Figure 1 shows a flow diagram of the participant assignment and outcome measures. In the study, 300 participants were enrolled; 28 participants were withdrawn in total, and 272 participants (90.7% in 300), including 544 eyes, were analyzed. Supplemental Table S2 shows baseline demographics and preoperative ocular biometry results. Sex, age, and preoperative ocular biometry did not differ significantly between the six protocols.

Figure 1. Flow diagram displaying participant assignment and outcome iterms in the six treatment protocols. Twenty-eight participants were withdrawn in total, including seven participants who were excluded due to abnormal suspensory ligament of the lens, retinopathy, or optic neuropathy, and twenty-one participants who were lost to follow-up due to personal reasons. VAS: visual analogue scale; VFQ-25: 25-item visual Function Questionnaire; EROV: extended range of vision.

Binocular uncorrected full-range visual acuity

The results of postoperative binocular full-range visual acuity are summarized in Table 1, including the mean visual acuity and the proportion of visual acuity ≤0.1 LogMAR in pairwise comparisons. Figure 2 presents the violin plot and pairwise comparison of postoperative binocular uncorrected full-range visual acuity among the six treatment protocols. Supplemental Figure S5 shows the proportion of patients with binocular uncorrected visual acuity ≤0.1 LogMAR. Regarding mean binocular UDVA and UNVA, the monovision protocol was significantly inferior to the other protocols (p < 0.05), while the difference was not statistically significant between the other five protocols (p > 0.05). Regarding the mean binocular UIVA, there were no significant differences between the trifocal and EROV protocols, which performed the best (p > 0.05), and no significant differences were found between the monovision and diffractive bifocal protocols, which performed the worst (p > 0.05). The monocular corrected distance visual acuity for all patients achieved 0.1 LogMAR. The differences were not significant across all protocols in terms of the monocular corrected visual acuity and the absolute refractive prediction error (Table 1).

Figure 2. Violin plot and pairwise Comparison of postoperative binocular uncorrected full-range visual acuity in the six treatment protocols. EROV: extended range of vision; LogMAR: logarithm of minimum angle of resolution.

Table 1. Postoperative visual acuity, defocus curve and monocular refractive prediction error in the six treatment protocols.

	Monovision protocol	Diffractive bifocal protocol	Mixed protocol	Refractive bifocal protocol	Trifocal protocol	EROV protocol	p Values
Binocular measurement
Patients, no.	43	46	45	47	46	45
Binocular uncorrected full-range visual acuity
UDVA (LogMAR)
Mean ± SD	0.09 ± 0.09^a	0.03 ± 0.07^b	−0.01 ± 0.08^b	0.01 ± 0.08^b	0.00 ± 0.04^b	−0.01 ± 0.06^b	<0.001
Range	−0.10 to 0.30	−0.10 to 0.20	−0.20 to 0.20	−0.20 to 0.20	−0.10 to 0.10	−0.10 to 0.10
UDVA ≤ 0.1 LogMAR
No. (%)	31 (72.1)^a	44 (95.7)^b	44 (97.8)^b	46 (97.9)^b	46 (100.0)^b	45 (100.0)^b	<0.001
95% CI (%)	[57.3, 83.3]	[85.5, 99.2]	[88.4, 99.9]	[88.9, 99.9]	[92.3, 100.0]	[92.1, 100.0]
UIVA (LogMAR)
Mean ± SD	0.18 ± 0.06^a	0.17 ± 0.10^a,b	0.10 ± 0.09^b,c	0.09 ± 0.10^c	0.02 ± 0.07^d	−0.02 ± 0.07^d	<0.001
Range	0.10 to 0.30	−0.10 to 0.40	−0.10 to 0.30	−0.10 to 0.30	−0.10 to 0.20	−0.10 to 0.10
UIVA ≤ 0.1 LogMAR
No. (%)	13 (30.2)^a	19 (41.3)^a,b	31 (68.9)^b,c	35 (74.5)^c,d	44 (95.7)^d,e	45 (100.0)^e	<0.001
95% CI (%)	[18.6, 45.1]	[28.3, 55.7]	[54.3, 80.5]	[60.5, 84.8]	[85.5, 99.2]	[92.1, 100.0]
UNVA (LogMAR)
Mean ± SD	0.21 ± 0.08^a	0.09 ± 0.10^b	0.08 ± 0.09^b	0.07 ± 0.07^b	0.06 ± 0.07^b	0.10 ± 0.07^b	<0.001
Range	0.10 to 0.40	−0.10 to 0.30	−0.10 to 0.30	−0.10 to 0.20	−0.10 to 0.20	0.00 to 0.20
UNVA ≤ 0.1 LogMAR
No. (%)	11 (25.6)^a	34 (73.9)^b,c	36 (80.0)^b,c	41 (87.2)^b,c	44 (95.7)^b	32 (71.1)^c	<0.001
95% CI (%)	[14.9, 40.2]	[59.7, 84.4]	[66.2, 89.1]	[74.8, 94.0]	[85.5, 99.2]	[56.6, 82.3]
Depth of focus (DoF) (D)
Cut off of 0.1 LogMAR	0.756	1.064	1.600	1.491	2.050	2.173
Cut off of 0.2 LogMAR	2.583	4.0139	4.211	4.316	4.529	3.636
Cut off of 0.3 LogMAR	4.313	4.858	5.236	5.223	>5.433	4.433
Area under the curve (AUC) (LogMAR/m)
fAUC	0.535	0.705	0.861	0.880	0.986	0.823
dAUC	0.220	0.310	0.392	0.366	0.396	0.357
iAUC	0.225	0.223	0.280	0.280	0.330	0.350
nAUC	0.090	0.173	0.189	0.234	0.260	0.116
Monocular measurement
Eyes, no.	86	92	90	94	92	90
Monocular corrected distance visual acuity
Mean ± SD (LogMAR)	−0.01 ± 0.06	−0.01 ± 0.06	−0.02 ± 0.06	−0.01 ± 0.07	−0.01 ± 0.05	−0.02 ± 0.05	0.495
Absolute refractive prediction error*
Mean ± SD (D)	0.14 ± 0.21	0.12 ± 0.21	0.14 ± 0.22	0.12 ± 0.2	0.16 ± 0.2	0.18 ± 0.23	0.112
≤0.25D, no. (%)	76 (88.4)	80 (87.0)	77 (85.6)	83 (88.3)	80 (87.0)	75 (83.3)	0.919
>0.25 and ≤0.5D, no. (%)	5 (5.8)	8 (8.7)	8 (8.9)	8 (8.5)	9 (9.8)	9 (10.0)
>0.5 and ≤1.0D, no. (%)	5 (5.8)	4 (4.3)	5 (5.6)	3 (3.2)	3 (3.3)	6 (6.7)

^a,b,c,d,eEach subscribe letter denotes a subset of intervention categories whose column do not differ significantly from each other at the 0.05 level in pairwise comparisons. *Absolute Refractive prediction error was calculated as the absolute difference between the measured postoperatively and predicted preoperatively refractive spherical equivalent. UDVA: uncorrected distance visual acuity (5 m); UIVA: uncorrected intermediate visual acuity (60 cm in the diffractive bifocal and mixed protocols, 80 cm in the remaining protocols); UNVA: uncorrected near visual acuity (40 cm); LogMAR: logarithm of minimum angle of resolution; SD: standard deviation; CI: confidence interval; EROV: extended range of vision; D: diopter; fAUC: full Area Under the Curve, dAUC: distance Area Under the Curve; iAUC: intermediate Area Under the Curve; nAUC: near Area Under the Curve.

Binocular uncorrected defocus curves

Figure 3 shows the postoperative binocular uncorrected defocus curves. Table 1 shows the DoFs and AUCs results. The smoothest defocus curve is obtained using the trifocal protocol. The defocus curves for the refractive bifocal, mixed, and EROV protocols were similar to that for the trifocal protocol, whereas the defocus curve for the monovision protocol was similar to that for the bifocal protocol. The trifocal protocol showed the best performance for most indicators of DoFs and AUCs, whereas the EROV protocol performed the best at DoF at a cut-off of 0.1 LogMAR and iAUC. The monovision protocol exhibited the most inferior performance for all indicators of DoFs and AUCs. With regard to the fAUC, the trifocal protocol was followed by a refractive bifocal protocol, mixed protocol, EROV protocol, diffractive bifocal protocol, and monovision protocol in sequence.

Figure 3. Postoperative binocular uncorrected defocus curve (mean) in the six treatment protocols. The abscissa indicates the defocus from +2.0 D to −4.0 D. The ordinate indicates the visual acuity (LogMAR). the different colored solid dots and lines represent defocus curve in different protocols. The black dashed lines separate distance, intermediate and near areas. The red dashed lines represent visual acuity cutoff lines. EROV: extended range of vision; D: diopter; LogMAR: logarithm of minimum angle of resolution.

Binocular visual function

No evidence of a statistically significant difference was found in the fusion point or divergence across the six protocols. The monovision protocol had the least favorable outcome at convergence, distance, and near stereopsis (p < 0.001), whereas there were no statistically significant differences between the other five protocols (p > 0.05) (Table 2 and Supplemental Figure S6 and S7).

Table 2. Postoperative binocular visual function: Fusion function and stereopsis in the six treatment protocols.

Binocular visual function	Monovision protocol	Diffractive bifocal protocol	Mixed protocol	Refractive bifocal protocol	Trifocal protocol	EROV protocol	p Values
Patients, no.	43	46	45	47	46	45
Fusion function (°)
Fusion point
Median [lower quartile, upper quartile]	0 [−2, 2]	0 [−1, 2]	0 [−1, 2]	0 [−2, 2]	0 [−2, 2]	1 [−2, 3]	0.838
Range	−5 to 5	−5 to 5	−5 to 4	−6 to 6	−5 to 3	−4 to 5
Convergence
Median [lower quartile, upper quartile]	12 [10, 18]^a	20 [15, 27]^b	19 [15, 23]^b	20 [14, 25]^b	19 [16, 24]^b	18 [16, 22]^b	<0.001
Range	5–28	7–30	9–30	8–30	9–30	11–30
Divergence
Median [lower quartile, upper quartile]	−5 [−6, −4]	−5 [−6, −4]	−5 [−6, −4]	−5 [−6, −4]	−5 [−6, −4]	−5 [−6, −4]	0.523
Range	−9 to −2	−8 to −3	−8 to −2	−8 to −2	−8 to −2	−8 to −1
Distance stereopsis no. (%)	a	b	b	b	b	b
≤60″	4 (9.3)	28 (60.9)	28 (62.2)	29 (61.7)	30 (65.2)	22 (48.9)	<0.001
80″–200″	13 (30.2)	16 (34.8)	14 (31.1)	18 (38.3)	16 (34.8)	21 (46.7)
400″–800″	23 (53.5)	2 (4.3)	3 (6.7)	0 (0.0)	0 (0.0)	2 (4.4)
>800″	3 (7.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Near stereopsis no. (%)	a	b	b	b	b	b
≤60″	2 (4.7)	29 (63.0)	26 (57.8)	32 (68.1)	31 (67.4)	25 (55.6)	<0.001
80″–200″	8 (18.6)	17 (37.0)	14 (31.1)	15 (31.9)	15 (32.6)	17 (37.8)
400″–800″	20 (46.5)	0 (0.0)	5 (11.1)	0 (0.0)	0 (0.0)	3 (6.7)
>800″	13 (30.2)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

^a,bEach subscribe letter denotes a subset of intervention categories whose column do not differ significantly from each other at the 0.05 level in pairwise comparisons. EROV: extended range of vision.

Binocular subjective spectacle independence rates

The postoperative binocular subjective spectacle independence rates at the distant, intermediate, near, and full-range are presented in Table 3 and Supplemental Figure S8. The binocular full-range subjective spectacle independence rates were sorted from highest to lowest as follows: trifocal protocol (84.8%), refractive bifocal protocol (80.9%), EROV protocol (80.0%), mixed protocol (73.3%), diffractive bifocal protocol (65.2%), and monovision (32.6%) protocols, with insufficient statistical differences between the former five protocols (p > 0.05).

Table 3. Postoperative binocular subjective spectacles independence rates, subjective questionnaires and dysphotopsia symptoms in the six treatment protocols.

	Monovision protocol	Diffractive bifocal protocol	Mixed protocol	Refractive bifocal protocol	Trifocal protocol	EROV protocol	p Values
Patients, no.	43	46	45	47	46	45
Binocular subjective spectacles independence rates*
Distant, no. (%)	32 (74.4)^a	38 (82.6)^a	37 (82.2)^a	39 (83.0)^a	42 (91.3)^a	43 (95.6)^a	0.083
95% CI (%)	[59.8, 85.1]	[69.3, 90.9]	[68.7, 90.7]	[69.9, 91.1]	[79.7, 96.6]	[85.2, 99.2]
Intermediate, no. (%)	18 (41.9)^a	30 (65.2)^a,b	33 (73.3)^b,c	37 (78.7)^b,c	39 (84.8)^b,c	43 (95.6)^c	<0.001
95% CI (%)	[28.4, 56.7]	[50.8, 77.3]	[59.0, 84.0]	[65.1, 88.0]	[71.8, 92.4]	[85.2, 99.2]
Near, no. (%)	20 (46.5)^a	39 (84.8)^b	37 (82.2)^b	39 (83.0)^b	39 (84.8)^b	36 (80.0)^b	<0.001
95% CI (%)	[32.5, 61.1]	[71.8, 92.4]	[68.7, 90.7]	[69.9, 91.1]	[71.8, 92.4]	[66.2, 89.1]
Full-range, no. (%)	14 (32.6)^a	30 (65.2)^b	33 (73.3)^b	38 (80.9)^b	39 (84.8)^b	36 (80.0)^b	<0.001
95% CI (%)	[20.5, 47.5]	[50.8, 77.3]	[59.0, 84.0]	[67.5, 89.9]	[71.8, 92.4]	[66.2, 89.1]
VAS score of Overall Satisfaction^#	a	a, b	a, b, c	c, d	b, c, d	d	<0.001
Mean ± SD	7.3 ± 1.4	7.5 ± 1.1	7.7 ± 1.2	8.3 ± 1.4	8.3 ± 1.3	8.9 ± 1.0
Median [lower quartile, upper quartile]	7 [6, 8]	7.5 [7, 8]	8 [7, 9]	8 [7, 10]	8 [7, 9]	9 [8, 10]
Range	4–10	6–10	5–10	6–10	6–10	7–10
VFQ-25 score^&	a	b	b, c	b	b, c	c	<0.001
Mean ± SD	79.81 ± 10.89	89.89 ± 4.49	91.65 ± 6.52	88.03 ± 7.29	90.56 ± 6.83	94.02 ± 5.00
Median [lower quartile, upper quartile]	79.42 [75.58, 89.04]	90.51 [85.91, 92.63]	92.50 [89.43, 96.01]	90.43 [81.52, 94.42]	92.65 [85.72, 95.56]	95.00 [93.16, 97.14]
Range	52.83–94.62	80.87–99.13	63.91–98.91	71.74–100.00	73.26–100.00	76.52–100.00
Dysphotopsia symptoms^§, no. (%)
Glare
None	29 (67.4)	27 (58.7)	25 (55.6)	27 (57.4)	32 (69.6)	35 (77.8)	0.154
A little	14 (32.6)	19 (41.3)	19 (42.2)	16 (34)	13 (28.3)	10 (22.2)
Mild	0 (0)	0 (0)	1 (2.2)	2 (4.3)	1 (2.2)	0 (0)
Moderate	0 (0)	0 (0)	0 (0)	1 (2.1)	0 (0)	0 (0)
Severe	0 (0)	0 (0)	0 (0)	1 (2.1)	0 (0)	0 (0)
Halos
None	34 (79.1)	27 (58.7)	29 (64.4)	36 (76,6)	27 (58.7)	35 (77.8)	0.070
A little	9 (20.9)	19 (41.3)	15 (33.3)	11 (23.4)	18 (39.1)	10 (22.2)
Mild	0 (0)	0 (0)	1 (2.2)	0 (0)	1 (2.2)	0 (0)
Moderate	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Severe	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Starburst
None	31 (72.1)	24 (52.2)	22 (48.9)	25 (53,2)	29 (63.0)	32 (71.1)	0.094
A little	12 (27.9)	21 (45.7)	22 (48.9)	21 (44.7)	16 (34.8)	12 (26.7)
Mild	0 (0)	1 (2.2)	0 (0)	1 (2.1)	1 (2.2)	1 (2.2)
Moderate	0 (0)	0 (0)	1 (2.2)	0 (0)	0 (0)	0 (0)
Severe	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)

^a,b,c,dEach subscribe letter denotes a subset of intervention categories whose column proportions do not differ significantly from each other at the 0.05 level in pairwise comparisons. *Binocular subjective spectacle independence rates at distant (walking or driving), intermediate (reading a newspaper or using a desktop computer), near (reading a book or using a cellphone) and full-range (the activities mentioned above). ^#The visual analog scale (VAS) of overall satisfaction was measured using a 0–10 rating scale representing the worst state [0] or the best state [10]. ^&The 25- item Visual Function Questionnaire (VFQ-25) was developed by the National Eye Institute (NEI). ^§Kruskal–Wallis nonparametric tests were applied for comparing the grade of the severity in postoperative binocular dysphotopsia symptoms. SD: standard deviation; CI: confidence interval; EROV: extended range of vision.

Subjective questionnaires

No statistically significant differences were detected between the EROV, refractive bifocal, and trifocal protocols, which acquired the top three VAS scores (p > 0.05) (Table 3). No statistically significant differences were detected between the EROV, mixed, and trifocal protocols, which acquired the top three scores of the VFQ-25 (p > 0.05) (Table 3 and Supplemental Figure S9).

Safety outcomes

No serious intraoperative or postoperative complications were observed, including rupture of the posterior capsule, posterior capsule opacification, IOLs dislocation or displacement, persistent high intraocular pressure, severe iatrogenic dry eye or secondary surgical interventions related to optical properties. The severity of postoperative binocular dysphotopsia symptoms was comparable in all protocols (glare p = 0.154, halos p = 0.070, starburst p = 0.094), and no patient reported unacceptable dysphotopsia symptoms disturbing their daily routine (Table 3 and Supplemental Figure S10).

Discussion

Age-related cataracts and presbyopia are non-negligible conditions that cause vision impairment, leading to a compromised quality of life in middle-aged or older people. This study aimed to evaluate the binocular visual quality between six common protocols of bilateral age-related cataract surgery with presbyopia correction to assist surgeons in achieving optimal surgical outcomes and meeting the high expectations of patients. Few researchers compared directly these six protocols in homogenized studies in the same period. This study focused on binocular visual quality of protocols rather than monocular visual quality of IOLs to explore the results of the reestablishment of central control of alignment by the binocular visual system. In this study, binocular visual quality was evaluated from different perspectives.

All treatment protocols were safe without obvious surgical complications. No differences were found in the baseline analysis or postoperative monocular refractive prediction errors between protocols. Therefore, the postoperative outcomes were comparable. Each protocol has advantages in different perspectives of binocular visual quality.

Some studies have reported that monofocal IOLs (non-presbyopia-correcting IOL) targeting monovision could provide better UIVA and UNVA than targeting emmetropia [21–24]. The monovision protocol can correct presbyopia, but it is not the preferred choice. The binocular uncorrected full-range visual acuity in the monovision protocol was inferior to other protocols with bilateral presbyopia-correcting IOLs implantation.

The UIVA in the diffractive bifocal protocol was lower than that in the trifocal, refractive bifocal, and EROV protocols because of the lack of intermediate foci. However, there was a slight improvement in binocular UIVA and equivalent outcomes in binocular UDVA and UNVA for the mixed protocol compared to the diffractive bifocal protocol. The design of a monovision or mixed approach could broaden the binocular vision range by utilizing binocular summation [25].

The trifocal protocol performed the best in full-range visual acuity as expected owing to the design of far, intermediate, and near foci [26,27]. The refractive bifocal protocol provided a similar full-range visual acuity as the trifocal protocol. It is possible that a neutral aberration profile compensating for corneal spherical aberration in asymmetric segmental refractive multifocal IOLs leads to satisfactory intermediate vision [18,28].

In addition, EROV IOLs could elongate the vision range from the distance through the intermediate but are limited at near distance [10]. And the micro-monovision protocol of EROV IOLs provides a superior range of visual acuity from far to near than the emmetropia protocol [29,30]. In our study, the EROV protocol showed excellent outcomes at all distances.

Defocus curves are used to evaluate consecutive visual functions at each simulated distance. Myriam et al. evaluated the monocular distance-corrected defocus curve of four presbyopia-correcting IOLs rather than binocular defocus curves [31]. The DoF assesses the dioptric range of defocus over a certain cut-off level as an indicator to interpret full-range visual acuity [32]. However, it is unable to evaluate visual acuity points below the cutoff line and cannot reflect the shifts of defocus curves. Using the AUC to evaluate the visual acuity capacity might be regarded as a supplemental method in such cases. In this study, we measured DoFs and AUCs simultaneously, with the former exhibiting a defocus range of cut-off visual acuity and the latter representing the specified visual acuity capacity during a specific distance (fAUC, from infinity to 25 cm; dAUC, from infinite to 2 m; iAUC, from 2 m to 50 cm; nAUC, from 50 cm to 25 cm). The distinguishing feature of each protocol at different distances is clarified by calculating the DoFs and AUCs. The results of our study indicate that different protocols may provide distinct advantages for different metrics at different distances.

Three-grade binocular visual function includes simultaneous perception, fusion function, and stereopsis. Binocular asymmetry leads to decreased binocular visual function. Few studies have focused on binocular visual function after refractive cataract surgery [33]. This study compared the three-grade binocular visual function among these six protocols. The results show that the monovision protocol targeted intentional anisometropia to increase the binocular DoF sacrificed binocular visual function (convergence and stereopsis). It has been reported that the greater the anisometropia in the monovision protocol, the better the visual range but the worse the binocular visual function [16,33–35]. The monovision protocol is not suited for patients requiring good binocular visual function. However, binocular visual function was not impaired in the micro-monovision EROV and mixed protocols was not impaired.

Subjective spectacle independence rate varies with different life demands and cognitive levels for each individual with the same visual acuity outcome in different studies. Binocular subjective spectacle independence rates at distant, intermediate, and near different protocols have their own characteristics owing to different design principles. Except for the monovision protocol, the other five protocols presented high subjective spectacle independence rates at full range, with no significant differences due to the small sample size. It was reported that the spectacle independence rate is from 27% in 1.16 diopters (D) to 81% in 2.27 D targeting monovision [36–38].

Overall satisfaction based on VAS is a much simpler and intuitive way to evaluate a patient’s subjective feelings. The National Eye Institute (NEI) sponsored the VFQ-25 questionnaire to measure the dimensions of self-reported vision-targeted health status that are most important for individuals with chronic eye diseases. For both the VAS and VFQ-25, the EROV protocol ranked the highest among the six protocols, which may be attributed to the design of micro-monovision, which was well tolerated and led to excellent outcomes at all distances. The monovision protocol ranked last in terms of VAS and VFQ-25 scores, which may be ascribed to bilateral asymmetry bilaterally. The small difference in near additional power in the mixed protocol did not result in patient dissatisfaction.

Frustrating dysphotopsia is a leading cause of patient dissatisfaction and IOL explantation. The cause of dysphotopsia with presbyopia-correcting IOLs may be related to the optic design of IOLs (edge design and index of refraction of the optic material). Some scholars have indicated that halos result from multiple focal points, and glare results from the forward light scatter of higher-order diffractive optics [39]. Each of which has its own special design for reducing the incidence of dysphotopsia. The incidence of dysphotopsia in different IOLs has varied in different studies. However, we did not find any notable differences among the six treatment protocols. Patients who choose presbyopia-correcting IOLs would not be substantially bothered by dysphotopsia. In addition, anisometropia may induce dysphotopsia during the monovision protocol.

However, this study has some limitations. First, the sample size is small. Second, a nonrandomized study with inconsistent IOL costs between protocols resulted in a risk of selection bias. Third, multiple comparisons increased statistical error. Taking into consideration these limitations, we would like to conduct a prospective, multicenter, randomized controlled trial with a large sample to confirm our results.

Conclusions

Each patient has a different educational background and economic status. Ophthalmologists can develop individualized treatment options to achieve excellent binocular visual quality to meet patients’ high requirements and expectations. All treatment protocols in the study corrected presbyopia with good full-range visual acuity, defocus curves, and spectacle independence rate, with a low incidence rate of dysphotopsia symptoms. Each protocol has its own advantages and candidates. Ophthalmologists can understand the different characteristics of different protocols based on the results of full-range visual acuity and defocus curves. The trifocal protocol showed the best performance in terms of binocular visual quality. For patients seeking superior outcomes regardless of cost, especially for patients with high expectations for full-range visual acuity, the trifocal protocol may be the best choice. The refractive bifocal, mixed, or micro-monovision EROV protocols could provide an approximate performance to the trifocal protocol. For patients whose requirement of intermediate visual acuity is not high, doctors can recommend protocols with bifocal IOLs. For patients who prefer diffractive bifocal IOL, the mixed protocol can improve binocular intermediate visual acuity on the premise of maintaining the same distance and near visual acuity as the diffractive bifocal protocol. For patients who prefer refractive bifocal IOL, the refractive bifocal protocol can help to achieve acceptable intermediate visual acuity without compromising distance and near visual acuity. For patients who need excellent distance to intermediate visual acuity without poor near visual acuity, ophthalmologists can recommend them to choose micro-monovision EROV protocol. Binocular asymmetry in mixed or micro-monovision EROV protocols does not affect binocular visual function or subjective satisfaction. The monovision protocol, which presented the worst binocular visual function of all, is an alternative method for presbyopia correction in patients who do not afford or are candidates for presbyopia-correcting IOLs.

Authors’ contributions

Hong Qi and Min Li contributed equally as co-corresponding authors responsible for the conceptualization, funding acquisition, project administration, resources, and supervision. Qianqian Lan and Fan Xu contributed equally as first authors, who were responsible for conceptualization, methodology, funding acquisition, formal analysis, writing-original draft, and writing-review. Song Sun, Siming Zeng, Yiyun Liu, Tingting Yang, Yaxin Li, Gang Yao, Baikai Ma, Boping Ma were responsible for investigation, methodology, data curation and formal analysis. Liyuan Tao and Xin Xiao were responsible for statistical analysis, validation, and visualization.

Acknowledgements

We thank Suosu Wei at the People’s Hospital of Guangxi Zhuang Autonomous Region for providing the statistical support. We thank Yufei Gao, Dehai Liu, Xiaoyu Wang, Chuhao Tang, and Yifang Zhou at Peking University Third Hospital, and Qi Chen, Chunli Diao, Jian Lv, Lanjian Li, and Zhou Zhou at the People’s Hospital of Guangxi Zhuang Autonomous Region for collecting the data. We thank all the participants for their involvement in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author [HQ] upon reasonable request.

Additional information

Funding

This study was supported by the Guangxi Medical Health Appropriate Technology Development and Application Project [S2020077], Science and Technology Plan Project of Qingxiu District in Nanning City [2020036], Natural Science Foundation of Guangxi Province [2021GXNSFBA075051], Guangxi Clinical Ophthalmic Research Center [AD19245193], National Natural Science Foundation of China [82171022, 81974128], and Capital Health Research and Development of Special Fund [2020-2-4097]. The funders had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation.