Visual Performance of a Polynomial Extended Depth of Focus Intraocular Lens

Purpose: To clinically evaluate a new extended depth of focus intraocular lens (ISOPURE, PhysIOL) with optic design modification based on a unique polynomial concept to improve intermediate vision while keeping the quality of distance vision equal to a monofocal lens. Methods: 18 patients (11 female, 7 male, mean age of 69.4 years) with bilateral cataract and regular corneal astigmatism ≤ 1.0 D underwent bilateral cataract surgery with ISOPURE implantation. Patients were followed for up to 6 months. Measured parameters were uncorrected (UDVA) and corrected distance visual acuity (CDVA), uncorrected (UIVA) and distance-corrected intermediate visual acuity at 80 cm and 66 cm (DCI80VA, DCI66VA) subjective refraction, defocus curve, tolerance of cylinder induction, and contrast sensitivity. The data from all implanted eyes (all-eyes) and a subset only including the first eye implanted for each patient were analysed. Results: The mean manifest refraction spherical equivalent (MRSE) decreased from 1.05 D pre-operatively to −0.15 D at the 4 - 6 month assessment, with 80.6% of eyes within ±0.50 D of emmetropia. At the final follow-up, mean (SD) monocular CDVA was −0.06 (0.04) logMAR, DCI80VA was 0.18 (0.08) logMAR and DCI66VA was 0.27 (0.13) logMAR. Despite a cylinder induction of −0.50 D, uncorrected distance visual acuity of 0.02 logMAR was still achieved. Conclusion: The ISOPURE intraocular lens provides excellent distance corrected visual acuity for far and intermediate distances along with high contrast sensitivity and good tolerance of residual refractive cylinder. contrast sensitivity tests were performed using CSV1000 Vision, USA) in photopic and mesopic conditions at the 1 - 2 M and 4 - 6 M follow up. Mesopic conditions were induced by adding mesopic filters (Vector Vision, USA) into the trial frame. Slit-lamp examination was performed, and all adverse events were documented at each visit.


Patients and Methods
Study design 18 patients were scheduled for bilateral cataract surgery and followed up at 1 to 2 weeks (1 -2 W), 1 to 2 months (1 -2 M), and 4 to 6 months (4 -6 M). All patients gave their informed consent to receive bilateral implantation of the ISOPURE IOL and the use of their post-operative data for publication purposes.
Polynomial technology The ISOPURE lens is an EDOF IOL based on the patented polynomial technology. Its aspheric optic is based on a 100% refractive mechanism and features complex polynomial surface design parameters to extend the depth of field compared to monofocal IOLs. With respect to the aspheric optic design of the monofocal parent device MicroPure (PhysIOL S.A.), the ISOPURE lens differs by the amount of spherical aberration (SA). The SA of both IOLs is negative (< 0) and decreases rapidly with the size of the aperture. However, the amplitude of the SA is comparatively more negative for the ISOPURE lens. In the case of the ISOPURE IOL, the residual SA of the pseudophakic eye is basically given by the SA of the IOL since the lens overcompensate the corneal SA. Thus, the residual SA is only slightly influenced by the type of cornea. Measurements on the optical bench show that compared to the monofocal parent device MicroPure, the depth of field is increased from 48% to 86% for corneal spherical aberrations ranging from 0 to 0.28 microns at 6 mm diameter according to information from manufacturer.
Inclusion and exclusion criteria The study included patients 45 years or older with bilateral cataract, no significant ocular comorbidities and regular corneal astigmatism ≤ 1.0 D (measured by automatic keratometry) in each eye. Exclusion criteria were negative corneal spherical aberration (measured with the Pentacam at a 4 mm pupil size); irregular astigmatism; degenerative ocular diseases (e.g. macular degeneration or other retinal or optic nerve disease) determined by optical coherence tomography (OCT) scanning; eyes that might require retinal laser treatment during the study or are at a greater risk of developing cystoid macular edema; previous intraocular or corneal surgery; traumatic cataract; history or presence of macular edema; instability of keratometry or biometry measurements; ocular hypertension; presence of glaucoma or clinically significant dry eye.
Intervention Experienced surgeons performed standard phacoemulsification under topical and intracameral anaesthesia through a 2.2 mm incision at the steep corneal meridian with in the bag IOL implantation. The preloaded IOL was delivered by a single-use injector (1.2.3, PhysIOL) and centred in the capsular bag ( Figure 2). Mean duration between first and second eye surgery was 6.0 ± 2.7 days.
Post-operative care The following topical medication was used: tobramycin/dexamethasone drops five times a day for the first 3 post-operative days and then three times a day until Open Journal of Ophthalmology Defocus curves were completed using a standard approach where the subject's eye is corrected to their best distance refraction followed by defocusing the eye by 0.5 D increments between −5.0 D to +1.5 D. Additionally, +0.25 D and −0.25 D lenses were used. The tolerance of induced astigmatism defocus was determined over the manifest distance refraction with minus cylinders from −0.25 D to −1.5 D (in 0.25 D steps) and with plus cylinders from 0.25 D to 1.5 D (in 0.25 D steps) at two-axis orientations, 90˚ and 180˚. The modified Snellen optotype with five letters per line was used to measure the visual acuity at each intolerance of induced astigmatism defocus and for defocus curve assessment. All visual acuities were expressed in logMAR.
Monocular and binocular contrast sensitivity tests were performed using CSV1000 (Vector Vision, USA) in photopic and mesopic conditions at the 1 -2 M and 4 -6 M follow up. Mesopic conditions were induced by adding mesopic filters (Vector Vision, USA) into the trial frame. Slit-lamp examination was performed, and all adverse events were documented at each visit.

Statistical analyses
This was the first clinical series exploring refractive and visual acuity outcomes following bilateral implantation of the ISOPURE EDOF IOL. Therefore, no formal sample size calculation was performed as the first implantation of the ISOPURE IOL in Europe was in July 2019. Results from the all-eyes dataset (both eyes for each subject included) and the first treated eye (for each subject) subsets are presented. The all-eyes set contains the monocular data from both eyes of each patient. Two interrelated data points are excluded, monocular data of the first treated eye subset includes only one eye per patient. The initial eye implanted for each patient was selected for this subset. The Kolmogorov-Smirnov test was used to test for the normal distribution of data. Except for the following observations, data was normally distributed (p > 0.05): Contrast sensitivity mesopic binocular at 6 cpd; Defocus binocular at 0 D; Defocus monocular at 0 D; Defocus monocular at −0.25 D. Data is presented as mean and standard deviation unless it is indicated otherwise.

Demographic data and preoperative clinical parameters
The analyses include outcomes of 36 eyes from 18 patients (11 female). The mean age and Standard Deviation (SD) of patients who completed the 4 -6 M follow-up were 69.4 (±6.9) years. Anterior chamber depth, axial length, white-to-white, keratometry, corneal astigmatism, and intraocular lens power were in the standard ranges for the first implanted eye subset and the all-eyes data set (Table 1) (Table 2).
Postoperative refractive astigmatism was stable for both data sets over the follow-up period ( Table 2). Refractive cylinder was smaller or equal to 0.25 D in 55% of eyes. The postoperative refractive cylinder was not bigger than 1.50 D for any of the patients (Figure 3(b)).

Monocular and binocular visual acuity
The visual acuity (VA) was stable during the follow-up period (Table 3). Monocular visual acuity for the first implanted eye data set improved from pre-operative CDVA of 0.26 (0.13) logMAR to −0.06 (0.04) logMAR at 4 -6 M. Mean DCI80VA was 0.18 (0.08) logMAR and DCI66VA 0.27 (0.13) logMAR at 4 -6 M. All-eyes achieved monocular VA of at least 0.3 logMAR at far distance Open Journal of Ophthalmology   and 80 cm, with and without correction, and more than 83% of eyes reached the same acuity at 66 cm (Figure 4(a)). Binocular VA in comparison to monocular VA improved only slightly, the binocular CDVA was −0.09 (0.06) logMAR, DCI80VA was 0.14 (0.08) logMAR and DCI66VA was 0.20 (0.11) logMAR (Table 3) at 4 -6 M. The vast majority of the patients had binocular visual acuity of at least 0.3 logMAR at all evaluated distances, both with and without distance correction (Figure 4(b)). Bilateral UDVA and CDVA were the same or only up to one line worse for 88.2% participants at the 4 -6 M assessment ( Figure 5).
Defocus curve The mean monocular defocus curve ranged from −1.0 D to +0.6 D for the visual acuity level of 0.     similar when analysing the monocular visual acuity after the induction of different values of positive cylinder. However, an axis of 180˚ showed much better visual acuity compared to the 90˚ axis, especially at cylinder inductions higher than +1.00 D (Figure 7(b)). Contrast sensitivity Mean monocular photopic contrast sensitivity at 1 -2 M was within the normal range for the age group 50 -75 years [11]. Mean monocular mesopic contrast sensitivity was worse at all spatial frequencies compared to photopic conditions. It was however around the normal average range [12] for a younger age group of 20 -50 years as there was no mesopic data available for the older age group (Figure 8(a)). Similar results were found for binocular contrast sensitivity at 4 -6 M (Figure 8(b)).
Additional procedures Six eyes (16.7%) from three patients required neodymium-doped yttrium aluminum garnet (Nd:YAG) laser posterior capsulotomy due to posterior capsular opacification (PCO). Four eyes were treated 3 -4 months after the initial surgery, and 2 eyes were treated after the study. Two eyes (5.6%) from one patient showed slight edema in the photoreceptor layer 1 week after surgery with regression after 2 months. This was probably due to non-compliance of treatment post-operatively. No further intervention was required.  [15].

Discussion
ISOPURE monocular and binocular CDVA were on average better by one line in comparison to results for AT LARA 829 MP and Tecnis Symfony. DCI66VA of these two IOLs was superior by 1 to 1.5 lines compared to the ISOPURE, resulting in 0.12 ± 0.18 logMAR and 0.18 ± 0.17 logMAR [15], respectively. In another study, Tecnis Eyhance ICB00 was comparable to ISOPURE at the intermediate distance where DCIVA was 0.27 ± 0.11 logMAR [14]. Here the ISOPURE CDVA also shows slight superiority against the Eyhance ICB00 [14]. Essentially, this study found that the ISOPURE CDVA was superior to the other EDOF IOLs, but at an intermediate distance of 66 cm, the AT LARA 829 MP and the Tecnis Symfony were superior to the Eyhance ICB00 and the ISOPURE, which achieved similar results. Monocular and binocular defocus curves of the ISOPURE IOL exhibited a very similar pattern to the AT LARA 829 MP and Tecnis Symfony [14] [15].
When compared to a study that evaluated bifocal, trifocal and EDOF lenses, our results were very similar to the Tecnis Symfony with higher levels of subjective and objective depth of field reported [16]. Due to the optical characteristics of EDOF IOLs it is expected that photopic phenomena will be minimal. However, the Tecnis Symfony IOL is still associated with some level of photic phe-  [21]. Since the ISOPURE lens is a fully refractive, aspherical lens based on polynomial technology and the Tecnis Symfony is a diffractive lens, we speculate that ISOPURE should induce less photic phenomena.
The visual acuity obtained with the ISOPURE after the induction of different values of positive and negative cylinder was dependent on the axis, with superior vision at axis 180˚ compared to at 90˚. Previously, Carones examined the impact on visual acuity with three multifocal intraocular lenses (MIOLs) and the Tecnis Symfony (EDOF) after the induction of different values of positive and negative cylinder [22]. In this study the ISOPURE performed better at an axis of 180˚ with similar results at an axis of 90˚ in comparison to the MIOLs. The outcomes for the ISOPURE were very similar in comparison to the Tecnis Symfony. Residual cylinders from +1.0 D to −1.25 D should therefore have no significant impact on visual acuity (better than 0.2 logMAR) and patient satisfaction [22]. As some studies have shown, especially with MIOLs, residual refractive errors have a significant negative impact on visual acuity outcomes [23] [24]. The ISOPURE lens may present an advantage as it has shown some range of tolerance.
Monocular photopic contrast sensitivity at 1 -2 months post-surgery was better by 0.5 logCS than monocular mesopic contrast sensitivity at spatial frequencies 6 -12 cpd, with similar results found for binocular contrast sensitivity at 4 -6 months. Contrast sensitivity at 3 cpd was almost identical between the testing conditions. In a previous study, a similar contrast sensitivity level under photopic and mesopic conditions was obtained between the EDOF Tecnis Symfony IOL and two trifocal IOLs (Panoptix, Alcon Laboratories Inc. and AT LISA tri 839 MP, Carl Zeiss Meditec AG) [17]. The ISOPURE results are consistent with these findings.
The limitations of this study are surely a small sample size and a lack of subjective assessment evaluating photic phenomena, quality of vision, and patient satisfaction. Since this was the first clinical experience there was no direct comparison to other monofocal or EDOF IOLs but future studies should focus on this as well as aligning the study design with the American National Standard for Extended Depth of Focus Intraocular Lenses (ANSI Z80.35-2018). Furthermore, in addition to visual acuity in the distance and intermediate range, data on near visual performance should be collected and assessed.

Conclusion
In conclusion, the ISOPURE EDOF IOL provides uncompromised distance vision and improves intermediate vision when compared with monofocal IOLs. As ISOPURE has no diffractive rings on the optic surface, it is expected to induce less photic phenomena. Future studies comparing its visual performance with other monofocal and EDOF IOLs, including a higher number of patients and longer follow-up time, as well as inclusion of patients with ocular comorbidities, would be valuable.