Anterior and posterior capsular opacification are still major complications of cataract surgery that occur due to the proliferation, migration, and differentiation of residual lens epithelial cells (LECs) [1, 2]. Contact with the intraocular lens (IOL) optic causes the LECs of the anterior lens capsule to undergo fibrosis, resulting in anterior capsule opacification (ACO) [1, 3]. This may in turn lead to contraction or retraction of the anterior capsule, and ultimately to a reduction in the free optic zone. Furthermore, anterior capsule contraction (ACC) may cause decentration of the IOL optic, as well as tilt of the IOL, and zonular stretching may lead to zonular rupture and subsequent dislocation of the IOL/capsular bag posteriorly [4–6].

The prevalence of posterior capsule opacification (PCO) has decreased due to technological and surgical improvements. Specifically, neodymium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy is an effective PCO treatment option [7]. However, treatment can lead to further complications, including cystoid macular edema, IOL subluxation and damage, elevation of intraocular pressure, and retinal detachment [8, 9]. For these reasons, it remains important to prevent PCO. To do so, IOL manufacturers continuously modify IOL designs and materials, and ophthalmic surgeons refine their surgical techniques to minimize the ACO and PCO risk.

Previous studies have reported that capsular fibrosis occurs 90–180 days after implantation [10], and the degree of ACC has been associated with many predictors, including individual, pathological, and surgical factors [11–13]. For instance, Hayashi et al. reported that the mean percentage reduction in the anterior capsule opening area was significantly greater in eyes with a silicone optic IOL than in eyes with an acrylic optic IOL. The same authors reported that the one-piece acrylic IOL appeared to withstand substantial post-operative capsular shrinkage, and that its optic and haptic design was not associated with ACC [3, 14]. In another study, Hayashi et al. observed no significant difference in ACC occurrence between acrylic IOLs with round-edge optics and those with sharp-edge optics [15]. Conversely, Sacu et al. reported that neither the material nor the haptic design of hydrophobic IOLs affected the occurrence of ACO or ACC [16]. A 2010 study found that greater ACC occurs after hydrophilic IOL implantation than after hydrophobic IOL implantation [17]. However, these studies only evaluated the material and edge type of the optics and the shape of the haptics, not the number and position of the haptics within the capsular bag. ACC occurs when the centripetal force of the anterior capsule opening margin (fibrotic change) differs from the centrifugal force of the capsular zonule [18, 19]. In this regard, to investigate whether the number and position of IOL haptics affected ACC, the present study evaluated the capsulorhexis aperture after implantation of three differently designed IOLs. The study also evaluated the rate of PCO for each IOL.

Two hundred thirty-six eyes of 202 patients were included in the study. The mean age of the patients at surgery was 65.43 years ±9.41 (SD) (range 55–75 years). One-hundred thirty-eight (58.5%) were women and 98 (41.5%) were men. At the 6-month follow-up examination, 186 patients (92.1%) were examined. No adverse event occurred during this study.

Anterior capsule opening size

Table 3 summarizes the mean (± SD) area of the anterior capsule opening in each of the three groups. The mean areas of the anterior capsule opening at 1 week, 2 weeks, and 6 months after surgery were 20.69 ± 1.50 mm², 17.17 ± 3.23 mm², and 17.01 ± 3.11 mm², respectively, in the IOL A group; 21.70 ± 0.86 mm², 21.07 ± 1.50 mm², and 20.48 ± 1.09 mm², respectively, in the IOL B group; and 21.43 ± 1.09 mm², 20.34 ± 1.60 mm², and 19.86 ± 1.58 mm², respectively, in IOL C group. The area of the anterior capsule opening decreased in all three groups from 1 week to 2 months after surgery, and from 2 months to 6 months after surgery. However, the reduction was greatest in the first 2 months after surgery (Fig. 2). The area of the anterior capsule opening after 1 week was smallest in the IOL A group, but no significant difference was observed among the three groups in this regard (p = 0.068; Table 3). At 2 and 6 months after surgery, the area of the anterior capsule opening was significantly smaller in eyes with an IOL A than in eyes with an IOL B or IOL C (p < 0.001). The reduction in the area of the anterior capsule opening between 1 week and 2 months after surgery was 3.53 ± 3.31 mm² (17.06% ± 15.99%) in the IOL A group, 0.62 ± 1.32 mm² (2.87% ± 6.03%) in the IOL B group, and 1.09 ± 1.53 mm² (4.72% ± 6.10%) in the IOL C group (Fig. 3). Thus, the IOL A showed the lowest anterior capsular stability after surgery, while the IOL B showed the greatest anterior capsular stability (p < 0.001; Table 3). In addition, with regards to the ACC that occurred between 1 week and 2 months after surgery, the IOL B showed a smaller reduction in the area of the anterior capsular opening than did the IOL C, though this was not significant (p = 0.093; Fig. 3).

Follow up	1wk	2 m		6 m
	CCC size	CCC size	Change from 1 week(percentage)	CCC size	Change from 2 months(percentage)
Precizon (IOL A)	20.69 ± 1.50	17.17 ± 3.23	−3.53 ± 3.31 (17.06 ± 15.99%)	17.01 ± 3.11	− 0.16 ± 1.31 (0.64 ± 6.21%)
Microflex (IOL B)	21.70 ± 0.86	21.07 ± 1.50	− 0.62 ± 1.32 (2.87 ± 6.03%)	20.48 ± 1.09	− 0.60 ± 1.51 (2.47 ± 6.91%)
Asphina (IOL C)	21.43 ± 1.09	20.34 ± 1.60	−1.09 ± 1.53 (4.72 ± 6.10%)	19.86 ± 1.58	−0.48 ± 1.19 (2.12 ± 5.25%)
P-value†	0.068	< 0.001	< 0.001	< 0.001	0.170

†one-way ANOVA

The anterior capsule opening decreases in area when LECs remaining on the IOL surface proliferate and undergo fibrous metaplasia upon contacting the IOL [24]. The imbalance between the centripetal force exerted by the LECs (fibrous metaplasia) and the centrifugal force exerted by the zonule induces ACC [18, 19]. Several reports have revealed that ACC occurs more frequently when using silicone IOLs or hydrogel optic IOLs, and that plate-haptic IOLs or thin optic IOLs cause less capsule dilation of the centrifugal haptics [3, 11, 12, 17, 25]. The association between silicone or hydrogel optics and ACC may be due to a weaker adhesion of the optic materials to the lens capsule. Weak adhesion may allow space for active proliferation of LECs and synthesis of extracellular matrix. In contrast, because acrylic optics adhere firmly to the capsule, and remnant LECs are only minimally exposed to various cytokines in the aqueous humor, fibrosis and contraction of the anterior capsule would be reduced when using such IOLs [3, 26, 27]. With specific regard to acrylic IOLs, hydrophilic varieties have shown significantly more frequent ACC than hydrophobic varieties [17], perhaps because hydrophobic IOL material prevents attachment of migrating epithelial cells on the optic and haptic surfaces. Other studies have reported that there is no difference between round- and sharp-edge optic design in terms of ACC prevalence [15, 16]. In summary, studies to date have indicated that optic surface contact with the anterior capsule, the convexity of the optic, and the edges of the optic and haptic, may play a role in LEC growth and anterior capsule contracture.

In the present study, we focused on the number and position of the haptics in the circular zonule, because ACO may be caused by LEC growth, whereas ACC is accelerated by the difference between the centripetal force of the anterior capsule opening margin (fibrotic force) and the centrifugal force of the capsular zonule [18, 19]. Some studies have suggested that four-haptic IOLs confer a large surface that contacts the posterior capsule, as well as more accurate IOL fixation within the capsular bag, leading to constant tension on the zonular fibers [28]. However, later studies reported that the number and design of haptics were not strongly associated with ACC [27]. In the present study, we noticed that it is not only the number of haptics that matters in ACC, but also the range of the zonule that is supported by the haptics and the location of the haptics within the zonule. In other words, there is little difference, in terms of IOL and zonule support, between an IOL with four haptics and one with two haptics if the haptics cannot support the zonule evenly. Since the zonule system has a circular configuration (360°) along the crystalline lens, force imbalances can occur with any number of haptics, unless the haptics are evenly positioned to support the whole zonule. In the case of the previously reported four-haptic IOLs (Akreos MI-60, BAUSCH+LOMB), even though there are four haptics, the interval between the haptics is larger in the long axis of the IOL, and the overall shape of the IOL is a rectangle with a long and short axis [27]. Thus, even if an IOL has four haptics, it may still provide less zonule support than an IOL with two haptics at a 180° interval, because the haptics are not evenly distributed in the zonule but only located on the long axis of the IOL. However, in the present study, IOL B (Microflex)—the four-loop haptic IOL—had four haptics, with an angle of around 90° between them (96° and 84°), suggesting that four haptics can support a circular zonule uniformly in 360°.

This is more pronounced when compared to the IOL A (2-loop plate haptic IOL). The two-loop plate haptic IOL had maintained a good anterior capsule opening 1 week after surgery, but this had decreased by 17.06% ± 15.99% after 2 months. In contrast, the four-loop plate haptic IOL only showed a 2.87% ± 6.03% decrease between 1 week and 2 months after surgery. In the comparison of the retro-illumination images (Fig. 1), the four-loop plate haptic IOL (b-1, b-2, b-3) showed a relatively circular anterior capsule opening after surgery, whereas the openings in the two-loop plate haptic IOL (a-1, a-2, a-3) and the two-plate haptic IOL (c-1, c-2, c-3) groups seemed to become elliptical over time. In particular, capsulorhexis margins appeared relatively stable where haptics were located. Where there were no haptics, the opening seemed to change to a narrower elliptical shape. Thus, it may be that the haptic does not support the zonule evenly and induces ACC. Furthermore, the IOL B group with the least ACC showed minimal change in SE value after surgery, suggesting that the haptic support also affects the position of the capsular bag, as well as the effective lens position (ELP).

Most commercially available IOLs are manufactured to be foldable within an injector to allow micro-incision cataract surgery (MICS). For this reason, IOLs are rectangular, and haptics are positioned at both ends of the long axis so that the IOL can be made smaller when folded. However, due to its shape, the four-loop plate haptic IOL used in the present study cannot be inserted into a 2.2-mm injector. Thus, an incision diameter of 2.4 mm was required to allow insertion. Although this may increase astigmatism after surgery, it may also decrease the risk of ACC and should be considered.

The four-loop plate haptic IOL maintained the anterior capsule opening well. However, the PCO generation was much more severe than in the other IOL groups. The Microflex—the four-loop plate haptic IOL used in the study—has a round-edged optic design, while the other IOLs have sharp-edged optic designs; this design is likely the reason for the severe PCO. Furthermore, the four-loop plate haptic of IOL B confers a large contact area with the capsule. This may allow space for active proliferation of LECs.

ACC can induce IOL decentration or tilting, and even IOL dislocation, whereas PCO, which is more common, can easily be treated using Nd:YAG laser posterior capsulotomy. Anterior capsule opening contraction can also be treated with Nd:YAG laser, and, more recently, femtosecond lasers have been used to enlarge a contracted capsule [29, 30]. Nonetheless, in severe cases, IOL tilting may not be improved after enlargement of the anterior capsule opening. Thus, it is important that surgeons prevent ACC as much as possible during surgery. Although many previous investigations have addressed ACC in Asian patients, the present study may be of significance as it is the first published study to focus on the location of IOL haptics and capsular bag stability. Many of the IOLs currently used may not provide an even force to support the zonule, because the haptics are not located at equal intervals around the haptics.

This study had several limitations. Firstly, the IOLs we compared differed in other characteristics besides haptic number and position. In particular, IOL B had a round optic edge that differed from those of the other IOLs. Therefore, it is problematic simply to compare the PCO among the three IOLs. Nonetheless, the present study may open a new line of inquiry based on the observation of previous studies that the optic edge does not affect the ACC [15, 16]. Secondly, although all known additional risk factors for ACC were excluded from the present study, there may be intrinsic factors other than IOL haptics that affect ACC. Thirdly, the ORGC size differed in the IOL A group (5.2 mm—0.2 mm smaller than in the IOL B and IOL C groups); this might have affected ACC. However, a previous paper reported that CCC size did not have a significant effect on capsule contraction. [31] Furthermore, significant ACC difference has been observed between groups with a CCC size of < 4.5 mm and those with a CCC size of 4.6–6.0 mm. [31] Based on previous reports, an ORGC difference of 0.2 mm would not have a significant effect on ACC.

In conclusion, the present study demonstrated that contraction of the anterior capsule opening was much smaller with the four-loop plate haptic IOL than with the two-loop plate haptic and two-plate haptic IOLs. ACC and IOL decentration vary depending on the location of the haptics within the capsular bag. Based on these results, when zonular weakness is detected during surgery, or when a condition that increases zonular instability is detected in the pre-operative examination, clinicians should consider selecting a four-plate haptic IOL that can support the zonule evenly.

Further studies, both clinical and histological, will be necessary to further elucidate the role of haptic position in ACC. It will also be necessary to develop a new IOL design that has evenly distributed haptics positioned within the capsular bag so that the rates of ACC and PCO can be lowered.

The number and position of haptics within the capsular bag may affect ACC. We assume that supporting the zonules evenly plays a role in anterior capsular stability.