Long Term Assessment of the Quality of Visual-related Daily Activities after ICL (V4C) Implantation for Myopia and Myopic Astigmatism

Background: The purpose of the study was to evaluate long-term quality of visual related daily activities after Central Hole Collamer Lens implantation to treat myopia and myopic astigmatism. Methods: This retrospective study included 46 eyes (23 patients) receiving an ICL-V4c implantation. The follow up time was at least 24 m. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), refraction, eye axis, intraocular pressure, endothelial cell density (ECD), vault, and the patients’ satisfaction related to vision related daily activities were recorded at 6 m and 24 m. Results: The mean spherical equivalents were -0.14 ± 0.21 D and -0.12 ± 0.33 D at 6 m and 24 m after surgery, respectively. UCVA of all eyes were equal to or better than preoperative BCVA. The BCVA at 6 m and 24 m after implantation were -0.03 ± 0.08 LogMAR, and −0.03 ± 0.11 LogMAR, respectively, which was statistically better (P = 0.031) than that of pre-operation value of 0.07 ± 0.12 LogMAR. There was no signicant differences (P > 0.05) between the pre operation and post operation ECD.At 24 m post operation, 10% of the patients complained of diculty driving at night, but most of patient had satisfactory or very satisfactory vision-related daily activity scores. Some patients, 13%, were worried about the long-term safety and ecacy of the V4c-ICL implantation. Conclusions: Patients were very satised with their vision related daily activities after V4c-ICL implantation. With time, some patients worried about the permanent safety and ecacy.


Background
The Vision Implantable Collamer® Lens (ICL, STAAR Surgical, Minrovia CA, USA) with a central arti cial hole is a promising next-generation surgical option for the treatment of moderate to high myopia, with excellent visual performance. Posterior chamber phakic intraocular lens (pIOL) implantation has become an important and inevitable choice for young patients with high myopia [1,2]. After implantation, the ICL-V4c closes the refractive system nodes, and has less image change and surgical injury, so it has high visual quality and better security compared to the laser refractive surgical [3,4]. An advantage of posterior chamber IOL implantation is that the integrity of eye is maintained and the surgery is safely reversible, unlike ocular lens extraction surgery in which the native ocular lens is removed. ICL is made from a collagen copolymer which is highly biocompatibile [5]. The new V4C lens is better than that the older V4 lens because it has a 0.36mm central hole [6,7]which allows for the circulation of aqueous in a natural manner minimizing iridectomy and reducing the risk of cataract.About the endothelial cell lossing, the U.S. FDA Trial demonstrated that it was 3.3±7.6% at one year postoperatively(90% con dence limits: 2.4% to 4.3%) [8]. Fernandes and colleague [9] reported that the mean endothelial cell loss varied from 9.9% to 3.7% at 2-4 years postoperatively,and that those loss was more prominented within the rst 1 to 2 years,but over time ,the ECD was stability or lower progression. Despite the advantages of V4c implantation, complications, such as cataract and elevated IOP levels were observed [10]. Objective and subjective short-term visual quality after ICL implantation has been studied extensively [11] . Some patients complained about halo or glare in dark environments [12]which can cause nighttime driving di culty, and some patients worried about the safety and the e cacy in the long-term of the implantation.
Long-term visual quality assessment of visual related daily activities in a complex living environment after ICL implantation have not been studied. To ameliorate this gap in knowledge, we assessed the quality of visual related daily activities 24 months after ICL-V4c implantation.

Patients And Methods
The current study included 46 eyes of 23 consecutive patients (mean age 24.04 ± 4.75 years, standard Inclusion Criteria. Inclusion criteria was: refraction did not change more than 0.5 D one year after surgery; BCVA was 0.5 or above; contact lenses were not worn for more than two weeks; no obvious eye diseases; a horizontal white-to-white distance between 10.5 and 12.5 mm; the number of corneal endothelial cells had to be greater than 2500mm -2; the central anterior chamber depth had to be more than 2.8mm. Intraocular Lens. ICL power calculation was performed using the instructions of the manufacturer (STAAR Surgical, Monrovia CA, USA). The emmetropia was the target refraction and the type of the ICL-V4c was chosen following the manufacturer's instructions and based on the anterior chamber depth and the horizontal corneal diameter. The horizontal white-to-white(W-T-W) distance was took by manual measurement.

Surgical Procedure
On the day of surgery, patients were given dilating and cycloplegic agents. Topical anesthesia was performed using 0.4% proparacaine before surgery. If a Toric ICL was implanted, the zero horizontal axis was marked by means of a slit-lamp preoperatively. A 3 mm clear corneal incision and the pre-installed ICL was slowly pushed into the anterior chamber through the incision. A special adjustment hook was used to adjust it into the posterior chamber, and then replaced the viscoelastic agent. All surgeries were performed by one experienced surgeon.

Statistical Analysis
All data were expressed as means ± SD. The preoperative and postoperative axial, IOP and ECD was analyzed using repeated analysis of variance (SPSS 17.0). The Student's T-test was used to test differences in the central vault, peripheral vaults and postoperative satisfaction score. A value of P < 0.05 was considered statistically signi cant.

Results
Refraction and Visual Parameters. Preoperative SE was -11.3 ± 3.7 D (-5.25 D to -15.75 D). SE were -0.14 ± 0.21 D (-1.00 to 0.75 D) and -0.12 ± 0.33 D (-1.00 to 0.50 D), postoperative 6 m and 24 m, respectively. Preoperative Log MAR UCVA was 1.4 ± 0.2 LogMAR ,−0.03 ± 0.07 LogMAR and -0.03 ± 0.09 LogMAR postoperative 6 m and 24 m, respectively. All of the 46 eyes had a UCVA equal to or better than the preoperative BCVA (Fig.1). The e cacy indexes were 1.21 and 1.24 (postoperative UCVA/preoperative BCVA). The BCVA at 6m and 24m after operation were -0.03 ± 0.08 LogMAR, −0.03 ± 0.11 LogMAR respectively, which was better than that of pre-operation (0.07 ± 0.12 LogMAR) (P=0.033).The safety index were 1.24 and 1.26(=postoperative BCVA/preoperative BCVA). The average preoperative axial length was 26.9 ± 1.3 mm, and the average postoperative axial length was 27.1 ± 1.3 mm at 24 m (P > 0.05). Intraocular pressure. There was no signi cant differences (P > 0.05) between the pre operation and post operation IOP (Fig. 2). Corneal Endothelial Cells Density There was no signi cant differences (P > 0.05) between the pre operation and post operation ECD (Fig. 3). Fig.3 The ECD before and 1m, 6m and 24m after V4c-ICL Vault The central vault, 0.46 ± 0.26 mm (0.1 to 0.70 mm) was signi cantly higher, P < 0.05 compared with the peripheral vault (Fig. 4) at all post operation times. During our follow-up, the central and peripheral vaults were gradually declined with time. At the rst 6m after V4c-ICL implantation, the central vault showed a quickly downward trend and then the change of vault was very slowly. In addition, our data showed that the high vault declined more obviously.  Table 1. Items one and two were related to near vision, items three through ve were related to far distance vision, item six was related to night vision, and items seven through eleven were related to middle-distance vision. Apart from the 10 % of patients that complained of di culty driving at night 24 m post operation, all of the other items received satisfactory or very satisfactory scores.
We also investigated whether patients had halos after surgery During the early postoperative follow-up period, the halos occurred in 12 patients (52.2%) in a dark environment, while halos were gradually reduced or disappeared over time. Only one patient had a halo that persisted in a dark environment. All of the patients gave satisfactory or very satisfactory scores for all the other items. A few patients, 13%, voluntarily informed us that they worried about the long-term e cacy of V4c-ICL implantation, however after six months post operation, there were no similar complaints. see Table 1 Discussion UCVA, BCVA and safety index measured in in the current study after V4c-ICL implantation in all eyes were equal or better than preoperative BCVA. No eyes had postoperative BCVA worse than preoperative BCVA. The majority of patients (95.65%) with BCVA improved in a row or more. The safety index at 6 m and 24 m post operation were consistent with a previous study [14] . No signi cant change was found in the eye axial length . which for patients with high myopia, is realted to refraction [15]. These results indicated that V4c-ICL was a safe and effective treatment for high myopia, and refraction was stable over time.
IOP for all patients was stable and similar to the preoperative level. A high IOP is one of the main problems after ICL implantation. The cause for early postoperative higher IOP levels include: excessive residual viscoelastic agent, an ICL that was too large, or a vault that was too high. The cause for mid-term higher IOP levels include steroid induced higher IOP; long term iris depigmentation, pigmentation blockage or chronic angle synechiae closure. All of the above risks were minimized due to the 0.36 mm central hole .
Maintenance of ECD is important for maintaining corneal transparency. Endothelial cells numbering about 5500 / mm2 lose their proliferation ability after birth and decrease normally by about 0.32% to 0.6% every year [16]. Intraocular surgery, corneal trauma, endophthalmitis and high IOP can the decrease ECD.In this study, we found that the number of corneal endothelial cells at 1m, 6m, and 24m after V4c-ICl implantation decreased by 3.92%, 4.83%, 5.02% respectively. Although not statistically signi cant, we found a trend towards a decrease in ECD after V4c-ICl implantation. We consider the factors of endothelial cell injury was surgical techniques, arti cial lens and change of aqueous humor of physicochemical properties in the early postoperative stage. While from 6m to 24m after V4c-ICL implantation, there had no obvious change about the ECD. Of course, a longer-term observation time and a larger sample size would be advantageous to document ECD changes with time.
Postoperative vault was a determinant of major complications after ICL surgery. Acceptable levels of postoperative vault for the V4C-ICL was de ned as 250 to 750 μm [17]. The vault was too low may increase the risk of cataract formation [18]. And the vault was too high will made the iris bulging forward, close to anterior chamber angle, and lead to the elevated IOP and iris dysfunction [19]. In the present study, we used ultrasound biomicroscopy to observe the distance between ICL and natural lens ,we found there were no V4c-ICL contact with lens directly .In the early period of postoperative follow-up, the vault was shown a downward trend, and quickly decreased at rst 3m after V4c-ICL implantation, and the higher vault mean more change. And then the change of vault gradually slowed over time. This result was consistent with the previous studies [10,19]. The peripheral vault was signi cantly lower than the central vault, which may ensure the optical imaging quality of V4C-ICL.Because the concave lens has the thin central area ( 40 um), the outer edge of optical thickness was 500-600um, and the haptic foot plates thickness was less than 100 um. This design allows the V4C-ICL to have the smallest refractive index, and ensure its high order aberration was smaller, to improve the quality of optical imaging.
Evaluation of visual quality after ICL implantation was the focus of many studies [14,15,20]. Objective parameters such as contrast sensitivity and high-order aberration after V4c-ICL implantation were measured [21,22]. There are no studies published regarding long-term vision-related daily activities, so we pursued this aim in the present study. Most of the patients we studied had satisfactory or very satisfactory visual function scores while 10% patients complained of di culty driving at night. Some patients complained of halos appearing in a dark environment. Haloes may arise from high contrast in a night time environment, and/or the central hole affecting diffraction causing the glare [12]. Our patients with glare complaints were given psychological counseling and with time the glare problems gradually disappeared without any treatment.
Some of the patients, 13%, voluntarily informed us that they worried about the permanent safety and e cacy after V4c-ICL implantation. During the 6 m follow-up, there were no similar complaints. Adequate preoperative communication, regular and long-term follow-up is important to relieve the patients' worries.

Conclusions
In summary, refraction and IOP were stable and there was no change in ECD or vault over a 24 m followup time. At 24 m post operation, 10% of the patients complained of di culty driving at night, but most of patient had satisfactory or very satisfactory vision-related daily activity scores. Some patients, 13%, were worried about the long-term e cacy of the V4c-ICL implantation. V4c-ICL implantation appears to be safe and effective, however a follow up period greater than 24 m and a larger sample size would are necessary to validate the long term safety and e cacy of the implantation.

Declarations Acknowledgments
This study was supported in part by the National Nature Science Foundation of China (no. 81660169) and the Department of Science and Technology of Guizhou (no. ZC220160310).

Funding
The project from the Department of Science and Technology of Guizhou (no. ZC220160310): design of the study and collection, analysis, and interpretation of data. The project from This study was supported in part by the National Nature Science Foundation of China (no. 81660169): write the manuscript and pay for a professional language editing service.
Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Authors' contributions Literature screening and selection was performed by SR Linghu and TX Liu. SR Linghu and YL Liao participated in the design of the study. SR Linghu drafted the manuscript.L Pan and R Shi carried out the statistical analysis. SR Linghu and TX Liu prepare and review of the manuscript. TX Liu has given nal approval of the version to be published. All authors read and approved the nal manuscript.
Ethics approval and consent to participate This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the A liated Hospital of Zunyi Medical College. Written informed consent was obtained from all patients after the nature and possible consequences of the study were explained.
Consent for publication Not applicable.

Competing Interests
The authors declare that there is no con ict of interests regarding the publication of this article.
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