ICL Postimplantation Decentration and Tilt in Myopic Patients with Primary Iridociliary Cysts

Purpose To observe the decentration and tilt of implantable collamer lens (ICL) as well as possible visual effects postimplantation in primary iridociliary cysts. Methods The present investigation was a retrospective cohort study. All 48 patients (91 eyes) who underwent ICL surgery at the Center of Refraction Surgery of Tianjin Medical University Eye Hospital between July 2018 and May 2020 were split into two groups based on the absence or presence of primary iridociliary cysts established by ultrasonic biological microscopy (UBM) examination. Intraocular pressure (IOP), corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), anterior chamber angle (ACA), anterior chamber volume (ACV), and anterior chamber depth (ACD) were recorded preoperatively and postoperatively at 1, 6, and 12 months. Additionally, we performed an analysis of the ICL vault, decentration, and tilt using a rotating Scheimpflug Oculus Pentacam camera system at 1, 6, and 12 months after surgery. Results No serious complications were observed. Significant postoperative improvement (P < 0.05) of UDVA was established in the two studied groups; however, we did not observe statistically significant intergroup differences (P > 0.05) throughout the entire research period. In each group, the preoperative ACA, ACV, and ACD were statistically significantly reduced (P < 0.05), but no such decrease was established between their postoperative values (P > 0.05). We observed no statistical differences between both groups with regard to their values of IOP, ACA, ACV, ACD, ICL vault, ICL decentration, and tilt at 1, 6, and 12 months after surgery. Similarly, no statistically significant within-group correlation (P > 0.05) of the decentration of ICL and the tilt and the CDVA values was established. Conclusion No postimplantation effect of ICL with a central hole on vision was established in myopia patients with primary iridociliary cysts, within certain limits of ICL decentration and tilt values.


Introduction
Myopia and astigmatism corrections have extensively been performed by the use of the implantable collamer lens (ICL). It is noteworthy that the use of ICL that features a central 0.36 mm hole (EVO-ICL) has eliminated the necessity for iridotomy and has allowed the maintenance of an appropriate aqueous fow, which is important for normal physiological processes in the anterior segment. EVO-ICL implant has been largely demonstrated to be an efcient and safe method of myopia correction [1][2][3][4].
Primary iridociliary cysts are frequently occurring benign uveal tumors. In a previous study, the reported primary iridociliary cyst incidence ranged from 4.9% to 64.3% in the general population [5] but was more common in high-myopia patients. Te majority of primary iridociliary cysts are shaded by the iris and can be found by ultrasonic biological microscopy (UBM). A cyst is characterized as solitary or multiple, round or ovoid, with a thin and hyperechoic wall and a sonolucent or hypoechoic interior ( Figure 1).
Teoretically, ciliary cysts could be in contact with ciliary sulcus-implanted ICL. Tus, it is logical to assume that iridociliary cysts would infuence the ICL implantation location. Furthermore, the progressive development of such ciliary sulcus cysts can induce distortion in the anatomy of the anterior chamber. Additionally, a haptic shift can be caused by cysts, and ICL might be prevented from stretching, elevating the vault, and causing ICL decentration and tilt and even pupillary block and/or glaucoma. Another adverse efect could be exerted by a large number of cysts located within the toric ICL (TICL) axis, which can lead to rotation disruption and result in astigmatism and glare and negatively afect visual acuity. Gharaibeh et al. [6] described a case, in which the intraocular lens placement was afected by a hidden iris cyst, causing glaucoma. Zeng et al. [7] reported a dislocation of the ICL caused by a cyst.
Our study aimed to elucidate the infuence that a primary iridociliary cyst could exert in terms of postoperative EVO-ICL decentration and tilt. We performed measurements of the preoperative and postoperative values of the intraocular pressure (IOP), visual acuity, anterior chamber angle (ACA), anterior chamber volume (ACV), anterior chamber depth (ACD), as well as of the postoperative ICL vault, decentration, and tilt of participants with and without primary iridociliary cysts who underwent EVO-ICL implantation. Te purpose of our research study was to assess whether iridociliary cysts had an impact on ICL decentration and tilt. We also aimed to determine whether decentration and tilt of the ICL were correlated with visual acuity.

Patients.
In the present retrospective study, we included patients with EVO-ICL implantation performed between July 2018 and May 2020 at Tianjin Medical University Eye Hospital. Te total number of enrolled patients was 48 (91 eyes), of which 13 were male (26 eyes) and 35 were female patients (65 eyes). We divided the patients into the following two groups. Te cyst group consisted of a number of 47 eyes with primary ciliary bodies and/or iris cysts detected by UBM. Te noncyst group included 44 eyes without cysts. To be recruited, the patients had to meet certain inclusion criteria, which are as follows: corrected distance visual acuity (CDVA) ≥10/20; stable refraction power for over two years (with a myopia increase ≤−0.5 D every year); the endothelial cell density (ECD) had to be more than 2000 cells/mm 2 ; and the value of ACD had to be 2.80 mm or higher. Te participants with eye diseases (such as cataracts and glaucoma) and systemic diseases (connective tissue disease and diabetes mellitus.) afecting the vision were excluded.
All investigators followed the principles of the Helsinki Declaration 2008, and Tianjin Medical University Eye Hospital's ethical committee approved the protocol (2021KY(L)-15).

Data Collection and Image
Analysis. Before surgery, the patients were subjected to a comprehensive ophthalmic evaluation, including CDVA, uncorrected distance visual acuity (UDVA), as well as standard slit-lamp microscopic, funduscopic, IOP (Canon, Japan), white-to-white (WTW), ECD (Topcon, Japan), and UBM (SW-3200, SUOER, China). Central corneal thickness (CCT) and axial length (AL) were determined by LENSTAR (Haag-Streit, Switzerland). Measurements of ACA, ACV, ACD, the vault of the ICL, the decentration of the ICL, and the tilt of the ICL were performed using Pentacam eye examination (Oculus Instruments, Germany). Te follow-up periods covered 12 months. In 1, 6, and 12 months postoperatively, we observed the changes in the CDVA, UDVA, IOP, ACA, ACV, ACD, and ICL vault, as well as the decentration and tilt of the ICL. All examinations were completed by the specialist with full expertise.
In the darkroom, the patients were asked to watch the indicator light continuously. During that time, the Pentacam visual segment analysis system was used to obtain the ICL 360degree full-circle Scheimpfug image by its built-in rotating Scheimpfug camera. Another built-in camera in the center of the Oculus Pentacam system was employed to detect pupil size and direction and maintain the control of eye fxation. When a good focus of the eye was achieved, 25 images which marked "OK" in the imaging quality specifcations (QSs) window were obtained per eye, and the horizontal and vertical meridians were selected. Te brightness and contrast of the images were enhanced to improve the clarity of the ICL anterior and posterior curve images for the acquisition of vault and tilt quantitative measurement data, with the maximum tilt value as the fnal result of the eye. Te clearest image of the ICL central hole was selected for quantitative measurement data acquisition of the decentration.
As can be seen in Figure 2(a), we obtained a high-quality anterior segment image, in which the ICL was located in the horizontal plane. Te ICL's central hole was determined by the most intensive refective point on its inner surface. Te vertical dotted line on this image is the corneal topographic axis (CTA), detected by Pentacam, which links the corneal vertex to the fxation point on the corneal topographer. In this study, we defned the ICL vault as being the height between the posterior curve of the ICL and the anterior curve of the crystalline lens on the CTA. Ten, we calculated the ICL decentration using the perpendicular distance between the CTA to the ICL's center hole. Te ICL central vault and decentration values were measured on the diagram of the Pentacam overview with the software program for image analysis of the device. We recorded the mean values of three measurements.
Furthermore, we adjusted two arcs to ft the ICL posterior and anterior curvatures with the ImagePro Plus 6.0 software. In this image, the intersecting arcs crossed the ICL plane segment. Te line perpendicular to the ICL plane indicated the ICL axis. Te angle between the ICL plane and CTA represented tilt, which was calculated as 90°and was subtracted from the value of the angle between the plane of the ICL and the CTA ( Figure 2).

Surgical Procedure.
At surgery initiation, we inserted an ICL into the anterior chamber via a 3.0 mm corneal incision utilizing a STAAR Surgical injector. After a regular amount of viscoelastic surgical agent (Amvisc; Bausch & Lomb, Shandong, China) was administered over the ICL, the ICL was adjusted into the posterior chamber, and we fushed the viscoelastic surgical agent out of the eye with a balanced salt solution. Postoperatively, we prescribed combined treatment with steroidal and antibacterial eye drops, as well as artifcial tears. Te same experienced surgeons (SZZ) performed all surgical operations.

Statistical
Analysis. SPSS 25.0 (IBM Corporation, USA) was used for the statistical analysis of the data. For our statistical analysis, CDVA and UDVA conversion were implemented to the logMAR scale. We adopted the Kolmogorov F02D Smirnov test to validate normal data distribution. In addition, we used nonparametric and parametric tests for comparisons of continuous variables, based on the specifc distribution of data. Te independent ttest or Mann-Whitney U test was conducted for continuous variables analysis. In contrast, the Fisher exact probability or the chi-square tests were implemented to compare categorical variables and conduct evaluations of the intergroup diferences. Te IOP, ACA, ACV, ACD, vault, decentration, and tilt of the ICL were evaluated using the multivariate analysis of variance (MANOVA) for repeated measures. Tukey's posthoc multiple comparison tests were used for pairwise comparisons. Spearman correlation analysis was performed to establish the correlation between CDVA and the ICL decentration and tilt. Statistical signifcance was determined at a P value of less than 0.05.

Results
In this retrospective study, we included a total number of 48 patients (91 eyes). Te baseline clinical preoperative and demographic indicators of the participants are listed in Table 1. In the intergroup comparison, no statistical differences were observed in the sex ratio, age, manifest spherical equivalent, CDVA, UDVA, IOP, AL, ACA, ACV, ACD, WTW, CCT, and ECD (P > 0.05).

Visual Outcomes.
Importantly, all of the performed implantations were successful, without postoperative complications throughout the entire follow-up period. No patients' postoperative CDVA declined, and no signifcant between-group diference was observed during the followup study (P > 0.05). We found statistically signifcant improvements in both groups' postoperative UDVA (P < 0.05); however, we detected no statistically signifcant between-group diference throughout the entire follow-up durations.
3.2. IOP, ACA, ACV, and ACD. We found no statistical diferences within the groups in the mean preoperative and postoperative (1, 6, and 12 months following surgery) IOP values (P > 0.05). A signifcant decline was noted in the preoperative values of ACA, ACV, and ACD (P < 0.05) in the two studied groups; however, no such diferences were detected between the postoperative values (P > 0.05). Additionally, we established no statistical diferences between-groups in their values of IOP, ACA, ACV, and ACD at the 1-, 6-, and 12month postoperative follow-up durations (Figure 3).

Correlation between Postoperative ICL Decentration and
Tilt and Visual Acuity. Te values of CDVA and the ICL decentration and tilt are listed in Table 2. We established no statistical correlation between the degree of ICL decentration and tilt and CDVA.

Discussion
Te application of implantable ICL is efective and safe for myopia and astigmatism. EVO-ICL's central port promotes aqueous humor circulation and thus prevents iridectomy. A large number of myopia patients have iridociliary cysts, but the implantation of ICL is not contraindicated in patients with primary iridociliary cysts. Nevertheless, no reports have been published on postoperative EVO-ICL decentration and tilt. Tus, careful observations were required to monitor any possible adverse efects on the visual acuity post-EVO-ICL implantation.
According to our results, good CDVA and UDVA were achieved in all patients, which were equal to or higher than their preoperative levels with no complications. Terefore, primary iridociliary cysts exerted no direct efects on visual performance after the surgical procedures of ICL implantation, which is consistent with previous fndings [8,9]. Our present fndings show the safety and efcacy of EVO-ICL implants applied to treat ametropia with iridociliary cysts.
In the preoperative and postoperative IOP values as well as those established at the 1-, 6-, and 12-month intervals, no statistical diferences were noted within or between groups. Our results regarding IOP are in line with previous research [8][9][10][11]. Te postoperative values of ACA, ACV, and ACD were statistically signifcantly lower than the preoperative in both groups. Nevertheless, no statistical diferences were observed between groups regarding ACA, ACV, and ACD. Our fndings indicated that the IOP, ACA, ACV, and ACD values in both groups, determined at the 1-, 6-, and 12month follow-up examination, were relatively stable. Tis was in agreement with an earlier report by Fernandez-Vigo et al. [12] , who detected ACA narrowing one month postoperatively. Still, ACA remained stable until the two-year follow-up examination. Elevated IOP was found to occur most frequently on the frst postoperative day due to retained viscoelastic material; long-term IOP elevation was established as related mainly to the angle closure and pupillary block [13]. ICL implantation pushed the iris forward, causing a reduction in ACA. However, IOP was normal, indicating that although the anterior chamber was changed, the circulation of the aqueous humor was not afected. Notably, an additional 360 μm-diameter hole was designed in the EVO-ICL, which was located in the optical center. Tat hole was created to facilitate the penetration of the aqueous humor, which reduced the risk of a postICL implantation IOP elevation. Our results showed that the postoperative morphological and structural changes of the anterior segment were stable in both the groups. Te presence of cysts and the changes in the ACA did not cause an increase in IOP. We established stable postoperative values of IOP, ACA, ACV, and ACD within the normal range.
We observed the vaults in the cyst group and the noncyst group at 1, 6, and 12 months postoperatively to assess the efect of cysts on ICL position. We found no statistically signifcant between-group diferences. Our study revealed that the presence of cysts exerted no direct impact on the postoperative vaults and the ICL haptic, which may be related to the cysts' peripheral location and relatively small size. Aman-Ullah et al. [14] described a case of binocular iris cysts with TICL implants, which remained stable over 15 months of follow-up examination. Moreover, the authors found that the isolated temporal iris cysts did not infuence the TICL location or the fnal visual outcome. Here, we established a continuous vault value decrease over time, but the vaults of the ICLs after surgery were within a normal range in all patients. Alfonso et al. [15] showed that a larger than 20 μm monthly decline occurred in the vaults during six months postoperatively; then, this decrease was reduced to approximately 2 μm a month at the 36-month follow-up examination. In another study, Chen et al. [16] followed up 270 eyes of 135 patients with iris cysts for one year postICL implantation and found that the changes in the ICL vault were less than 30 μm. In the present study, we selected ICL based on WTW, ACD, crystalline lens rise, diopter, pupil size, and age. After surgery, the values of the ICL vaults were from 200 to 890 μm, with no signifcant change, showing no infuence exerted by the presence of the cyst on that parameter. Additionally, Zeng et al. [7] revealed that many factors, including WTW, STS, ACD, and ICL size, afected the arch vaults after ICL implantation. Te leading causes of the abnormal vaults were age, lens thickness, WTW measurement error, and the presence of a ciliary body cyst. In our work, we carefully considered preoperatively all these factors, which contributed to an excellent postoperative outcome.
Te position of the ICL is of great importance since it may afect CDVA and facilitate the postoperative occurrence of complications such as glaucoma and cataracts [11,17]. A primary iridociliary cyst, particularly in the ciliary sulcus, may prevent the ICL haptic from stretching. Alternatively,   the ICL haptic may not be on the same height, causing the ICL to be decentered and tilted. It is possible for persistent cyst growth in the ciliary sulcus to cause displacement of the ICL, thereby increasing its tilt. In refractive surgery, accurate centration is considered to be critical for achieving optimal visual outcomes [18][19][20]. An alignment should exist between the corrected center position and the optical axis or the corneal anterior surface and the optical axis intersection point [21]. He et al. [22] suggested that an evaluation of the ICL position was feasible based on its central-hole relation to the corneal center. In this respect, based on the visual axis, Holladay et al. [23] proposed a standardized approach for intraocular lenses (IOLs) tilt and decentration measurements, which was associated with CTA or corneal light refex axis. Zhang et al. [24] suggested that IOL displacement measurements related to CTA were the most appropriate postoperative approach for the evaluation of visual acuity. Accordingly, we assessed the ICL decentration and tilt relative to the CTA. Nevertheless, it was difcult to determine the center location of conventional ICLs like V4 with a Pentacam [12,25]. Notably, the EVO-ICL featured a central hole, whose inner surface in the Scheimpfug image had a strong refection. Terefore, we were able to observe ICL directly in its central location in the posterior chamber with the use of a Pentacam. Hence, in the current study, we had the opportunity to directly evaluate the ICL decentration in the posterior chamber according to the center hole position in the Scheimpfug images. Such a procedure is noninvasive, noncontact, convenient, and objective; it also has good reliability and repeatability. At 1, 6, and 12 months postoperatively, the decentration and tilt of ICL were quantitatively measured with a rotating Scheimpfug camera. We found no statistically signifcant between-group diference. Our results showed that the range of decentration was from 0.03 to 0.66 mm, while the degree of tilt was from 0.22°to 6.27°. Te position of the ICL in all patients was relatively stable after the surgery. Our study revealed no efect was exerted by iris cysts on the ICL decentration and tilt.
Te infuence of the central-hole position on clinical visual indicators was assessed in two earlier studies [26,27]. In one of these investigations, Pérez-Vives et al. [26] conducted an experiment with a visual simulator; they observed no infuence of the three predetermined hole locations on the visual acuity. In the second of the aforementioned studies, Park et al. [27] evaluated the degrees of the decentration of ICL (i.e., within a hole diameter of 1, 2, or 3 from the pupil center) in three groups and found no statistical diference between them. In our study, the degree of ICL decentration and tilt and the CDVA were not statistically signifcantly correlated. Te small sample size used in the present study was its major limitation. Nonetheless, the values of the coefcients of the correlation between the ICL tilt and decentration and CDVA were insignifcant. Tus, a correlation between the ICL tilt and decentration and the value of CDVA was nearly absent. Although the present research fndings indicated that the ICL decentration and tilt had no efect on the fnal visual outcome, some studies showed that the EVO-ICL central-hole location could infuence the postoperative glare and quality of life. Martínez-Plaza et al. [28] evaluated the efects of the specifc EVO-ICL central-hole position on vision quality. Tey showed that the quality of life, as measured by a pertinent questionnaire, was worse when the central hole had a higher position on the vertical axis and the presence of upward decentration of the central hole, which was established by using the visual axis as a reference basis. Te decentration of the ICL hole can lead to bothersome glare and eventually adversely afect the patient's quality of life. Eppig et al. [29] concluded that the presence of an ICL's center hole might result in the perception of ghost images (positive dysphotopsia) and stray light despite the absence on-axis of such efects. In an experimental study conducted by Eom et al. [30], ring and arc images were generated by the ICL hole; the cause for this efect was the light refracted from the central hole's inner surface. It is possible that the ring dysphotopsia could have been associated with arc image merging, which was induced by oblique light. Terefore, the increase in the angle of incidence of incoming light induced higher stray light radiant power. It is noteworthy that this phenomenon might have critical importance in various glare patterns. Considering the possible major infuence on the patient-perceived quality of life, in spite of the excellent visual outcomes of the central-hole ICL implantation, we strongly advise that patients diagnosed with cysts should be meticulously examined preoperatively and be informed of the potential risks. For instance, a risk could be posed by an alteration in the size of a cyst; moreover, the ICL haptics might be situated in close proximity or even exactly on a cyst position. In this case, the iris root could be pressed forward, causing ACA closure or narrowing. Furthermore, the ICL haptics might be more likely to break a capsule of a cyst, whose leaking out fuid might cause a severe infammatory process. Terefore, its preTICL surgery design should be appropriate, and the degrees of rotation, as well as the direction, should be selected and developed in such a way as to avoid the intraimplantation connection between cysts and the haptics. All postoperative changes in IOP, ACA, and visual outcomes should be monitored during an extended follow-up period.

Conclusion
In summary, the implantation of EVO-ICL in myopic patients sufering from primary iris ciliary body cysts is an efective and safe treatment. Moreover, certain degrees of postoperative ICL decentration and tilt have no adverse efects on visual acuity. Several limitations of the present study should be acknowledged, including its brief follow-up duration, limited sample size, and a small cyst-afected area; additionally, this investigation was a retrospective cohort study, and UBM was not used for the detection of the size and location changes in the iris ciliary body cysts. Moreover, the visual quality and the quality of life were not checked. Terefore, further research studies are required to confrm our present fndings.

Data Availability
Te datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Conflicts of Interest
Te authors declare that they have no conficts of interest.