Posterior chamber phakic intraocular lens implantation after laser in situ keratomileusis.

BACKGROUND: To assess the multicenter outcomes of posterior chamber phakic intraocular lens implantation with a central hole (EVO-ICL, STAAR Surgical) for patients undergoing previous laser in situ keratomileusis (LASIK).
METHODS: This case series enrolled 31 eyes of 21 consecutive patients undergoing EVO-ICL implantation to correct residual refractive errors after LASIK at 7 nationwide major surgical sites. We investigated safety, efficacy, predictability, stability, and adverse events at 1 week, 1, 3, and 6 months postoperatively, and at the final visit.
RESULTS: The mean observation period was 1.6 ± 1.8 years. Uncorrected and corrected visual acuities were - 0.14 ± 0.11 and - 0.22 ± 0.09 logMAR at 6 months postoperatively. At 6 months postoperatively, 81% and 100% of eyes were within ± 0.5 D and ± 1.0 D, respectively, of the targeted correction. We found neither significant manifest refraction changes of 0.05 ± 0.38 D from 1 week to 6 months nor apparent intraoperative or postoperative complications in any case.
CONCLUSIONS: Our multicenter study confirmed that the EVO-ICL provided good outcomes in safety, efficacy, predictability, and stability, even in post-LASIK eyes. Therefore, EVO-ICL implantation may be a viable surgical option, even for correcting residual refractive errors after LASIK. Trial registration University Hospital Medical Information Network Clinical Trial Registry (000045295).

Background

Laser in situ keratomileusis (LASIK) has been extensively recognized as an effective and predictable surgical procedure for correcting refractive errors worldwide. However, myopic regression of the initial surgical effect can influence the efficacy, predictability, and long-term stability of this surgery leading to deterioration in visual performance and subsequent patient dissatisfaction. While the LASIK procedure is largely standardized with predictable and stable outcomes, attributable to improvisations in laser settings, nomograms, and sophisticated centration and eye-tracking systems, it is well-known that some regression does occur after LASIK surgery, especially when the amount of refractive correction is large [1-7]. We previously demonstrated that conventional LASIK offered outcomes with a high degree of safety throughout a 12-year follow-up period, and that most eyes showed some amount (approximately 10%) of refractive regression at 12 years after LASIK [7]. Although the exact mechanism for refractive regression remains unanswered, anterior corneal bulging, epithelial hyperplasia, development of new stromal collagen, nuclear sclerosis of the crystalline lens, and elongation of axial length might play an essential role in myopic regression [8-16]. In addition, enhanced ablation might sometimes induce an additional biomechanical weakening of the cornea, resulting in subsequent refractive instability and further myopic regression, especially when corneal tissue is subtracted excessively from the residual cornea [8-10].

The EVO Visian implantable collamer lens (EVO-ICL, KS-Aquaport™, STAAR Surgical, Monrovia, CA, USA), a posterior chamber phakic intraocular lens, may have advantages over enhanced LASIK in terms of maintaining biomechanical integrity of the cornea, especially in eyes with a thin cornea requiring enhancement surgery, since ICL surgery requires no surgical tissue subtraction. Indeed, we found no significant changes in corneal biomechanical parameters following ICL implantation, not only in normal eyes but also in keratoconic eyes, suggesting that ICL surgery may be a safer surgical approach than enhanced LASIK from a biomechanical standpoint [17]. Nevertheless, there are only a few studies that report detailed outcomes of current EVO-ICL implantation to correct residual refractive errors, possibly due to the limited number of ICL surgeries in post-LASIK eyes. Accordingly, it may give us essential insights into further understanding the prognosis of these sequential surgical outcomes. The goal of this study was to retrospectively evaluate the clinical outcomes of current EVO-ICL implantation to correct residual refractive errors after LASIK in a large cohort of patients presenting at major surgical facilities in Japan. This multicenter study was performed under the auspices of the Japan ICL Study Group. To our knowledge, this is the first multicenter study as well as the largest case series to investigate the outcomes of modern ICL implantation in post-LASIK eyes.

Methods

Study population

We registered the study protocol with the University Hospital Medical Information Network Clinical Trial Registry (000045295). Patients who underwent implantation of the EVO-ICL for the correction of residual refractive errors after LASIK at 7 major nationwide institutions (Kitasato University Hospital, Sanno Hospital, Sapia Tower Eye Clinic Tokyo, Nagoya Eye Clinic, Chukyo Eye Clinic, Tane Memorial Eye Hospital, and Fujimoto Eye Clinic) from January 2016 to December 2020, and who completed a 6-month follow up, were enrolled consecutively. We included patients with unsatisfactory correction with spectacles or contact lenses, 20 ≤ age ≤ 50 years at the time of ICL surgery, stable refraction and corneal shape, anterior chamber depth (ACD) ≥ 2.8 mm, and endothelial cell density (ECD) ≥ 1800 cells/mm2 for ICL implantation. We excluded patients with a previous history of ocular surgery, except for previous LASIK, corneal diseases, cataract, glaucoma, uveitis, or other concomitant eye diseases. The Institutional Review Board at Kitasato University Hospital approved this retrospective review of the clinical charts. The study adhered to the tenets of the Declaration of Helsinki and written informed consent was obtained for this surgery from all patients after explaining the possible consequences.

Outcomes measures

Preoperatively, at 1 week, at 1, 3, and 6 months postoperatively, and at the last visit (spanning more than 6 months), we measured the logarithm of the minimal angle of resolution (logMAR) of uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), the manifest spherical equivalent (MSE), the intraocular pressure (IOP) using a non-contact tonometer, the ECD (preoperatively and 6 months postoperatively) using a non-contact specular microscope, and the vault between the anterior surface of the crystalline lens and the posterior surface of the ICL using an anterior segment optical coherence tomographer, in addition to routinely conducted ophthalmic examinations. We grouped all available visit data according to the closest time point.

ICL power calculation and size selection

ICL size (12.1, 12.6, 13.2, and 13.7 mm) was determined mainly based on the manufacturer’s nomogram using the white-to-white (WTW) distance and the ACD measured with a scanning-slit light corneal tomographer or the anterior segment optical coherence tomographer. ICL power was selected using an online calculation and ordering system provided by the manufacturer based on a modified vertex formula [18, 19]. We principally selected the toric model ICL in eyes with manifest astigmatism of 1 diopter (D) or more and the non-toric model ICL in eyes with that of less than 1 D.

Surgical procedures

Details of the surgical techniques were described in our preceding reports [20-23]. In brief, we applied dilating and topical anesthetic agents on the day of surgery then implanted a model V4c or V5 ICL through a 3- to 3.2-mm temporal clear corneal incision after injection of a viscosurgical substance into the anterior chamber. Next, we inserted the ICL into the posterior chamber, replaced the viscosurgical substance with a balanced salt solution, and administered a miotic agent. We topically applied antibiotic and steroidal medications 4 times daily for 1 week, and reduced the dose gradually.

Statistical analysis

Normality of all data samples was checked using the Shapiro-Wilk test. Data that did not fulfill the criteria for normal distribution, were analyzed using the Wilcoxon-signed rank test to compare the pre- and post-surgical data between the two groups. The Kruskal-Wallis test was used to evaluate the time-course of changes, with the Steel-Dwass test employed for multiple comparisons. Unless otherwise indicated, the results are expressed as mean ± standard deviation, and a value of P < 0.05 was deemed statistically significant.

Results

A total of 31 eyes from 21 patients (11 of men and 20 of women) met the inclusion criteria of our study. The mean duration from LASIK to ICL surgery was 13.9 ± 4.1 years (range, 9.0 to 23.0 years). The mean observation period was 1.6 ± 1.8 years. Table 1 shows the preoperative baseline demographics of the study population following LASIK. The preoperative spherical and cylindrical refraction were − 1.68 ± 0.86 D (range, − 0.50 to − 4.25 D) and 0.39 ± 0.49 D (range, 0 to 1.75 D), respectively. Five eyes (16%) and 2 eyes (6%) showed residual corneal thickness of 450 µm and 400 µm or less, respectively. Figure 1 shows the distributions of the spherical and cylindrical ICL power. Non-toric and toric ICL models were used in 28 eyes (90%) and 3 eyes (10%), respectively.

Table 1

Preoperative demographics in eyes undergoing implantable collamer lens (ICL) implantation following laser in situ keratomileusis (LASIK)

Characteristic	Mean ± standard deviation (95% CI, range)
Age	41.4 ± 7.1 years (95% CI 27.5 to 55.3 years, range 30 to 57 years)
Gender	Male: Female = 11: 20
Manifest spherical equivalent	− 1.87 ± 0.91 D (95% CI − 3.65 to − 0.09 D, range − 4.75 to − 0.75 D)
Manifest cylinder	− 0.39 ± 0.49 D (95% CI 0.57 to − 1.35 D, range 0 to − 1.75 D)
UDVA	0.51 ± 0.28 logMAR (95% CI 1.06 to − 0.04 logMAR, range 1.00 to 0.10 logMAR)
CDVA	− 0.21 ± 0.10 logMAR (95% CI − 0.01 to − 0.41 logMAR, range 0.10 to − 0.30 logMAR)
White-to-white distance	11.7 ± 0.5 mm (95% CI 10.72 to 12.68 mm, range 10.8 to 12.8 mm)
Anterior chamber depth	3.12 ± 0.27 mm (95% CI, 2.59 to 3.65 mm, range, 2.80 to 3.72 mm)
Mean keratometric readings	39.27 ± 1.37 D (95% CI, 36.58 to 41.96 D, range, 34.97 to 41.75 D)
ICL size	12.1 mm, 13 eyes (42%), 12.6 mm, 7 eyes (35%), and 13.2 mm, 7 eyes (23%)
ICL spherical power	− 2.38 ± 1.03 D (95% CI − 4.39 to − 0.37 D, range − 5.00 to − 1.00 D)
ICL cylindrical power	1.38 ± 0.48 D (95% CI 0.44 to 2.31 D, range 1.00 to 2.00 D)

ICL = implantable collamer lens; CI = confidence interval; D = diopter; LogMAR = logarithm of the minimal angle of resolution; UDVA = uncorrected distance visual acuity; CDVA = corrected distance visual acuity

Fig. 1

Distributions of the spherical (a) and cylindrical (b) implantable collamer lens (ICL) power

Safety and efficacy outcomes

At one week, 1, 3, and 6 months postoperatively, and at the last visit, 90%, 90%, 90%, 90%, and 71% of eyes, and 68%, 66%, 74%, 74%, and 14% of eyes, respectively, had a UDVA of 20/20, and 20/16 or better (Fig. 2a). UDVA was − 0.14 ± 0.11, − 0.14 ± 0.09, − 0.15 ± 0.12, − 0.14 ± 0.11, and 0.00 ± 0.18 logMAR, at 1 week, 1, 3, and 6 months postoperatively, and at the last visit, respectively (Kruskal-Wallis test, P = 0.158). The 6-month postoperative UDVA was significantly better than the preoperative UDVA (P < 0.001). The efficacy index (mean postoperative UDVA/mean preoperative CDVA) was 0.87 ± 0.16 at 6 months postoperatively. At 6 months postoperatively, 28 eyes (90%) showed no change in CDVA, and 2 eyes (6%) gained 1 line, while 1 eye (3%) lost 1 line, but no eyes had lost more than 1 line (Fig. 2b). The 6-month postoperative CDVA was 20/16 in the eye that lost 1 line. CDVA was − 0.23 ± 0.10, − 0.22 ± 0.09, − 0.22 ± 0.08, − 0.22 ± 0.09, and − 0.17 ± 0.07 logMAR, at 1 week, 1, 3, and 6 months postoperatively, and at the last visit, respectively (P = 0.539). We found no significant difference between the preoperative CDVA and the 6-month postoperative CDVA (P = 0.477). The safety index (mean postoperative CDVA / mean preoperative CDVA) was 1.04 ± 0.17 at 6 months postoperatively.

Fig. 2

Standard graphs for reporting refractive surgery outcomes. a Cumulative percentages of eyes attaining specified cumulative levels of uncorrected distance visual acuity (UDVA); b Changes in corrected distance visual acuity (CDVA); c A scatter plot of the attempted versus the achieved manifest spherical equivalent correction; d Distribution of spherical equivalent refractive accuracy; e Distribution of refractive astigmatism; f Time course of changes in the manifest spherical equivalent

Predictability and stability outcomes

A scatter plot of the attempted versus the achieved manifest spherical equivalent correction, distribution of spherical equivalent refractive accuracy, and distribution of refractive astigmatism are shown in Fig. 2c–e, respectively. At one week, 1, 3, and 6 months postoperatively, and the last visit, 90%, 97%, 94%, 81% and 71% of eyes, and 97%, 100%, 97%, 100%, and 86% of eyes were within ± 0.5 D and ± 1.0 D, respectively, of the attempted spherical equivalent correction.

The time-course change in the manifest spherical equivalent is shown in Fig. 2f. At one week, 1, 3, and 6 months postoperatively, and at the last visit, the manifest spherical equivalent was − 0.25 ± 0.28, − 0.15 ± 0.27, − 0.07 ± 0.38, − 0.20 ± 0.35, and − 0.48 ± 0.55 D, respectively (P = 0.076). Changes in manifest spherical equivalent refraction from 1 week to 6 months were 0.05 ± 0.38 D.

Intraocular Pressure

The IOP was 10.5 ± 1.9, 10.3 ± 1.9, 10.0 ± 1.8, 10.0 ± 2.4, and 9.8 ± 2.1 mmHg, at 1 week, and 1, 3, and 6 months postoperatively, and the last visit, respectively (P = 0.576). No significant increase in the IOP (> 25 mmHg) occurred in any case throughout the observation period.

Endothelial Cell Density

The ECD did not change significantly, from 2697 ± 231 cells/mm2 preoperatively to 2701 ± 226 cells/mm2 at 6 months postoperatively (P = 0.554). Thus, the mean percentage of endothelial cell loss was – 0.4 ± 6.3% at 6 months postoperatively.

Vault

The ICL vault was 354 ± 178, 327 ± 162, 292 ± 150, 281 ± 152, and 187 ± 86 µm, at 1 week, and 1, 3, and 6 months postoperatively, and the last visit, respectively (P = 0.079). Figure 3 shows the postoperative distribution of the ICL vault. Neither excessive-low vault (< 45 µm) nor excessive-high vault (> 1000 µm) requiring ICL exchange was found in any case.

Fig. 3

Distribution of eyes according to the vault after implantable collamer lens (ICL) implantation in post-laser in situ keratomileusis (LASIK) eyes

Secondary surgeries / adverse events

We found no obvious intraoperative complications, such as an upside-down ICL insertion or traumatic cataract formation. We observed mild glare or halo in all eyes, especially at night in the early postoperative period, but no definite postoperative complications, such as symptomatic or asymptomatic cataract formation, pigment dispersion glaucoma, pupillary block, severe symptomatic glare or halos, retinal detachment, ICL re-rotation, ICL exchange, or significant endothelial cell loss (≥ 15%), throughout the follow-up period were noted in this series.

Discussion

According to our experience, modern EVO-ICL surgery performed well in safety, efficacy, predictability, and stability, even correcting residual refractive errors in post-LASIK eyes. In addition, no obvious intraoperative or postoperative complications were noted in any subject. Therefore, ICL implantation may be one of the feasible surgical options to correct residual refractive errors after LASIK surgery. This information will be clinically helpful for the prognosis of these sequential approaches for correcting residual refractive errors after LASIK.

Table 2 shows a summary of the outcomes of ICL surgery following corneal-based refractive surgery. Until now, there have been only a few case reports [24-26] and a few case series on the outcomes of ICL implantation following corneal refractive surgery [27-29]. It has been demonstrated, in case reports, that ICL implantation was beneficial for correcting residual refractive errors following radial keratotomy (RK) [24, 25] and hyperopic LASIK [26]. Chen et al. showed in a case series of 19 eyes of 12 patients undergoing ICL implantation after corneal refractive surgery, that UDVA and CDVA at the last visit were 0.64 ± 0.24 and 0.79 ± 0.24, respectively, and that 52.63% and 73.68% of eyes were within ± 0.5 D and ± 1.0 D of the predicted spherical equivalents, respectively [27]. Alfonso et al. described, in a study of 20 eyes undergoing excimer laser surgery or RK following cataract surgery, that the efficacy and safety indices were 0.98 and 1.13 after excimer laser ablation, 1.04 and 1.11 after RK, and that the virgin cornea, excimer laser, and RK groups showed better predictability and accuracy, with 96.2% spherical equivalent within ± 1.0 D [28]. Moshirfar et al. recently reported, in a study of 13 eyes of 7 patients undergoing ICL implantation after LASIK or PRK, that the efficacy and safety indices were 0.99 ± 0.42 and 1.15 ± 0.38, respectively, at 1 year postoperatively [29]. Our findings were in good agreement with all previous results of ICL surgery in post-corneal refractive surgery eyes. Although the possible risk of complications such as cataract formation and the subsequent prognosis were decreased by the introduction of lens models incorporating a central port (such as the V4c and V5 models) [30], a further long-term follow-up is still necessary to confirm these findings. Pérez-Vives et al. simulated visual quality using an adaptive optics visual simulator, showing that ICL surgery is one of the favorable alternatives to correct myopic residual errors after LASIK, especially for high myopia [31]. Hence, ICL implantation can be viable treatment alternatives to correct residual refractive errors in post-LASIK eyes, especially when the residual corneal thickness is insufficient for the enhanced ablation.

Table 2

Summary for the outcomes of implantable collamer lens (ICL) implantation following laser in situ keratomileusis (LASIK)

Author	Year	Type	Previous surgery	Period (months)	Eyes	Age (years)	MSE (D)	UDVA	CDVA	Within ± 0.5 D	Within ± 1.0 D	Complications
Srinivasan et al. [24]	2008	V3 (non-hole)	RK	3 to 7	4	33 to 45	+ 5.31  + 3.25 to + 9.0	20/24 20/30 to 20/20	20/24 20/30 to 20/20	100%	100%	None
Kamiya et al. [25]	2008	V4 (non-hole)	RK	12	1	49	+ 4.75	0.8 decimal	1.2 decimal	100%	100%	None
Kamiya et al. [26]	2010	V4 (non-hole) with LRIs	LASIK	10	1	48	+ 1.75	1.0 decimal	1.2 decimal	100%	100%	None
Chen et al. [27]	2016	V4 (non-hole)	RK, PRK, LASIK, TOGCA, LASEK	39.05 ± 19.22	19	37.54 ± 7.59	− 7.45 ± 3.02	0.64 ± 0.24 decimal	0.79 ± 0.24 decimal	52.63%	73.68%	1 eye cataract RD
Alfonso et al. [28]	2018	V3 to V5 (non-hole and hole) after IOL implantation	LASIK, PRK	19.02 ± 22.98	12	59.34 ± 11.44	− 1.23 ± 2.18 sphere  − 1.02 ± 1.37 cylinder	0.68 ± 0.23 decimal	0.78 ± 0.14 decimal	91.7%	91.7%	None
			RK	16.06 ± 9.53	8		− 1.13 ± 2.72 sphere  − 3.16 ± 1.96 cylinder	0.73 ± 0.19 decimal	0.78 ± 0.16 decimal	100%	100%	None
Moshirfar et al. [29]	2020	N.A (non-hole)	LASIK, PRK	12	13	33.7	− 12.42 ± 1.81	0.99 ± 0.42 efficacy index	1.15 ± 0.38 safety index	7 eyes (100%)	7 eyes (100%)	None
Current		V4c, V5 (hole)	LASIK	6	31	41.4 ± 7.1	− 1.87 ± 0.91	− 0.14 ± 0.11 logMAR	− 0.22 ± 0.09 logMAR	81%	100%	None

MSE = manifest spherical equivalent; D = diopter; UDVA = uncorrected distance visual acuity; CDVA = corrected distance visual acuity; RK = radial keratotomy; LRIs = limbal relaxing incisions; LASIK = laser-assisted in situ keratomileusis; logMAR = logarithm of the minimal angle of resolution; TOGCA = topography-guided customized ablation; LASEK = laser-assisted subepithelial keratomileusis; RD = retinal detachment; IOL = intraocular lens

This study has several limitations. Firstly, we performed this study in a retrospective fashion. Although this is a multicenter study in a successive cohort of post-LASIK patients undergoing ICL implantation, a prospective randomized controlled study would be better to obtain robust outcomes. Secondly, the sample size was relatively small, possibly due to the limited number of general ICL surgeries in post-LASIK eyes; this was one of our motivations in performing a multicenter study under the auspices of the Japan ICL Study Group. It should be noted that this is also the largest case series to assess the ICL surgical outcomes in post-LASIK patients. A multicenter study may reflect the actual status more accurately than a single-center study because the former may be less influenced by their individual surgical skills and experiences than the latter. Thirdly, the follow-up period was limited. A prolonged observation is still necessary to confirm the long-term outcomes in this study population. Fourthly, we included both eyes of the same patient undergoing ICL implantation following LASIK. However, we obtained similar outcomes when only one eye was chosen randomly from each patient (Additional file 1: Fig. S1). Hence, we enrolled both eyes when applying for this analysis, which was not uncommon for most published studies on refractive surgery considering that the number of patients undergoing ICL surgery after LASIK is limited. Fifthly, we did not perform dilation to check the degree of toric ICL rotation as the postoperative UDVA was excellent. Therefore, this study has no data on toric lens stability.

Conclusions

In conclusion, our multicenter study showed that the current EVO-ICL provided good outcomes for correcting residual refractive errors in post-LASIK eyes without significant complications throughout the follow-up period. Our findings support the view that current ICL implantation is one of the feasible surgical options for correcting residual refractive errors after LASIK. However, we should be aware that the cost-effectiveness and the long-term outcomes of ICL surgery remain to be answered; additional prolonged careful follow-up in a large cohort of post-LASIK patients will be necessary to clarify these points.

Additional file 1: Figure S1. Standard graphs for reporting refractive surgery outcomes when only one eye was chosen randomly from each patient. a Cumulative percentages of eyes attaining specified cumulative levels of uncorrected distance visual acuity (UDVA); b Changes in corrected distance visual acuity (CDVA); c A scatter plot of the attempted versus the achieved manifest spherical equivalent correction; d Distribution of spherical equivalent refractive accuracy; e Distribution of refractive astigmatism; f Time course of changes in the manifest spherical equivalent.