- Email: [email protected]
Impacts of Implantable Collamer Lens V4c Placement on Angle Measurements Made by Optical Coherence Tomography: Two-Year Follow-up
Accepted Manuscript Impacts of implantable collamer lens V4c placement on angle measurements made by optical coherence tomography: two-year follow up José Ignacio Fernández-Vigo, Ana Macarro-Merino, Cristina Fernández-Vigo, José Ángel Fernández-Vigo, Lucía De-Pablo-Gómez-de-Liaño, Cristina Fernández-Pérez, Julián García-Feijóo PII:
S0002-9394(17)30263-5
DOI:
10.1016/j.ajo.2017.06.018
Reference:
AJOPHT 10176
To appear in:
American Journal of Ophthalmology
Received Date: 6 April 2017 Revised Date:
14 June 2017
Accepted Date: 19 June 2017
Please cite this article as: Fernández-Vigo JI, Macarro-Merino A, Fernández-Vigo C, Fernández-Vigo JÁ, De-Pablo-Gómez-de-Liaño L, Fernández-Pérez C, García-Feijóo J, Impacts of implantable collamer lens V4c placement on angle measurements made by optical coherence tomography: two-year follow up, American Journal of Ophthalmology (2017), doi: 10.1016/j.ajo.2017.06.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT ABSTRACT Purpose: To determine iridocorneal angle changes produced after two years of implantable collamer lens® (ICL) V4c (STAAR Surgical AG) placement by Fourier-domain optical coherence tomography (FD-OCT). Design: Prospective interventional case series.
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Methods: In 54 eyes of 27 myopic subjects FD-OCT (RTVue®, Optovue Inc.) iridocorneal angle measurements were made before, and 1 month, 3 months, 1 year and 2 years after ICL implant. Trabecular-iris angle (TIA), angle opening distance 500 µm from the scleral spur (AOD500) and iridotrabecular contact length (TICL) were compared among these time points and the quadrants nasal, temporal and inferior.
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Results: Preoperative TIAs were 49.5 ±8.7, 48.3 ±9.6, and 49.1 ±8.6 degrees for the nasal, temporal and inferior quadrants (P<.001). Corresponding values were 29.9 ±10.4, 28.4 ±10.8 and 28.8 ±9.7 degrees at 1 month and 27.3 ±8.8, 26.8 ±8.1 and 28.9 ±7 degrees at 2 years of follow-up indicating angle narrowing of 39 to 45% and no further narrowing beyond 1 month in the nasal (P= .133), temporal (P= .376) and inferior (P= 1.000) quadrants. Trabecular-iris contact (TIC) was observed in 8 eyes of 8 subjects mostly only in the temporal quadrant. Mean TICL failed to vary during follow-up (307 ±288 µm at 3 months and 225 ±142 µm at 2 years, p= .159).
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Conclusions: In response to ICL V4c implant, considerable angle narrowing was detected at 1 month but this narrowing remained stable at 2 years. In the 8 cases of TIC, no progression of contact was observed beyond 3 months postimplant.
ACCEPTED MANUSCRIPT Title: Impacts of implantable collamer lens V4c placement on angle measurements made by optical coherence tomography: two-year follow up
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Authors: José Ignacio Fernández-Vigo,1,2 Ana Macarro-Merino,2 Cristina Fernández-Vigo,2 José Ángel Fernández-Vigo,2,3 Lucía De-Pablo-Gómez-deLiaño,2 Cristina Fernández-Pérez,4 Julián García-Feijóo.1
1. Department of Ophthalmology, Hospital Clínico San Carlos and Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain. 2. Centro Internacional de Oftalmología Avanzada, Madrid, Spain.
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3. Department of Ophthalmology, Universidad de Extremadura, Badajoz, Spain.
Corresponding author: José Ignacio Fernández-Vigo
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4. Department of Preventive Medicine, Hospital Clínico San Carlos and Instituto de Investigación sanitaria (IdISSC), Madrid, Spain.
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Centro Internacional de Oftalmología Avanzada c/Zurbano 71, 28010 Madrid, Spain email: [email protected]
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Short title: Two-year OCT angle changes after implantable collamer lens Financial support: None
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The authors declare no conflicts of interest
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ACCEPTED MANUSCRIPT INTRODUCTION For the treatment of myopia, hyperopia and astigmatism, the phakic Visian implantable collamer lens® (ICL, STAAR Surgical AG) is rapidly gaining popularity. This option has several benefits over keratorefractive procedures including rapid visual recovery, and a better and more stable visual outcome.1-6
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ICL was designed as a precrystalline posterior chamber lens. The latest model V4c has a central hole or AquaPORT® to facilitate aqueous humor outflow and thus avoid the need for iridotomy.7-8 However, this new ICL model still has several drawbacks common to all posterior chamber lenses, and may induce complications such as raised intraocular pressure (IOP), pigment dispersion, abnormal pupil dynamics, cataract or endothelial abnormalities.6,9-11 There are two main concerns about posterior chamber lenses related to the final vault distance between the posterior ICL surface and the anterior crystalline surface.12-13 When this distance is insufficient, the risk of developing cataract is increased,11,14,15 while if there is excessive distance, angle closure, or pupillary block, is induced, possibly leading to glaucoma.16
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To date, only a few studies have examined anterior chamber angle modifications produced in response to ICL implantation. Early research efforts were based on gonioscopy examination17,18 with its shortcomings of subjectivity and patient discomfort. This was followed by studies based on ultrasound biomicroscopy (UBM) in which angle narrowing was observed by Chung et al.19 and, in patients with a shallow anterior chamber, by Lim et al.20 More recently, angle narrowing has been observed using a Scheimpflug device in response to the V4c ICL model.21 However, optical coherence tomography (OCT) offers improved resolution over both the UBM and Scheimpflug-based techniques.
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METHODS
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In a prior study,22 using Fourier-domain OCT (FD-OCT) we determined angle changes produced 3 months after ICL (V4c) implant. Given the results of this study clearly indicated angle narrowing, the present study sought to determine whether this narrowing would continue beyond this time point and to identify factors predictive of postimplant angle closure. A further objective was to follow patients who developed trabecular-iris contact (TIC) soon after implant surgery.
For this prospective interventional case series study, we recruited 27 patients (54 eyes) consecutively scheduled for ICL implant to treat myopia over the period June 2013 to February 2015 at the Centro Internacional de Oftalmología Avanzada, Madrid (Spain). Of these 27 patients, 19 were participants of our previous 3-month study.22 The study protocol adhered to the tenets of the Declaration of Helsinki and received IRB approval prospectively from the University of Extremadura (Badajoz, Spain). This observational study was registered in www.clinicaltrials.gov. Before implant surgery, written informed consent was obtained from each participant. Inclusion criteria were an age between 20 and 45 years, and a stable refractive state over the last 2 years. Subjects were excluded if they had an anterior 2
ACCEPTED MANUSCRIPT chamber depth < 2.8 mm, an endothelial cell count <2000 cells/mm2, hyperopia, a history of glaucoma or of ocular inflammation, or preexisting corneal disease.
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Examination procedures
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The characteristics of the V4c model ICLs implanted in these myopic patients have been described in our previous study.22 In each participant, the ICL was aligned with the 180º meridian and rotated a maximum of 5-10º (Figure 1). Lens rotation was assessed after pupil dilatation by biomicroscopy. All lens implant operations were conducted by the same surgeon (AMM). The surgical technique consists of a corneal paracentesis and intracamerular lidocaine 1%. The anterior chamber is filled with a hydroxypropyl methylcellulose solution as viscoelastic (OcuCoat, Bausch & Lomb, Rochester, New York, USA). Then, through a 3.2 mm clear corneal temporal incision, the ICL is inserted with an injector (STAAR Surgical Co.) and correctly positioned with the help of a hook. Once remnants of viscoelastic have been removed with saline, 1 mg of cefuroxime sodium is injected and incisions are hydrated to complete the surgical procedure. Postoperative treatment was 4 drops per day of moxifloxacin for 7 days and tobramycin and dexamethasone 0.1% 4 times daily and tapered over 30 days.
All patients underwent a standard examination before surgery consisting of general medical history, visual acuity, anterior slit-lamp biomicroscopy, posterior segment ophthalmoscopy, tonometry (Goldmann), and endothelial cell count (Tomey®, Nagoya, Japan).
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Pentacam® was used to measure anterior chamber depth (ACD) from the endothelium (Oculus Inc., Wetzlar, Germany). Axial length, white-to-white (WTW) distance and pupil diameter were measured using the IOL Master® (Carl Zeiss, Meditec, Dublin, CA, USA).
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Visual outcome was assessed by measuring uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) using the logMAR scale. After implant surgery, follow-up visits were conducted at 1 and 3 months, and 1 and 2 years. In each postsurgery visit, the following were recorded: UCVA, BCVA, refractive error, IOP, lens vault, endothelial cell count and FD-OCT iridocorneal angle measurements. Fourier-domain optical coherence tomography For iridocorneal angle measurements, we used RTVue® 100 (Optovue Inc., Fremont, CA, USA). This instrument has an 840 nm laser diode; scan speed is 26.000 A-scans per second, and axial resolution is 5 - 8 µm. Exams were performed with the CAM-L lens on the nasal, temporal and inferior quadrants (3, 6 and 9 o’clock) under mesopic conditions with the device’s software set to Angle mode. The area captured was 3 x 2.3 mm centered at the limbus. Images were obtained by a trained examiner (JIFV) with the patient looking at a fixed point inside the device. Each quadrant was scanned three times and the image showing the best quality and least noise selected for subsequent angle measurements. 3
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The measurements made were: trabecular-iris angle (TIA), tracing a 500 µm line from the angle recess toward the Schwalbe's line and another line on the surface of the iris to the point crossing the first line (Figure 2, upper row); angle opening distance 500 µm from the scleral spur (AOD500) as the distance at right angles from the trabecular meshwork 500 µm anteriorly from the scleral spur to the anterior iris surface (Figure 2, inferior row); iris thickness (IT500) at the perpendicular point 500 µm to the scleral spur (Figure 2, inferior row left); and trabecular-iris contact length (TICL) as the linear distance of contact between the trabecular meshwork and the iris (Figure 3 and 4).23 Only narrow angles show TIC such that TICL can only be measured in eyes with this characteristic feature. The vault was also measured manually in the FD-OCT images by tracing a line from the center of the anterior pole of the crystalline lens to the posterior pole of the ICL.
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Statistical analysis
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Statistical tests were performed using the software package SPSS® (Statistical Package for the Social Sciences, v18.0; SPSS Inc., Chicago, IL). Univariate correlations were identified through Pearson's correlation test, or Spearman’s Rho test in the case of non-normally distributed data (spherical error and AOD500). Generalized estimating equations were employed to control for intereye correlation, assessing postsurgery differences in measurements between follow-up sessions. Presurgery differences in angle measurements between quadrants were determined by ANOVA with Bonferroni correction. The sample size needed to detect a 30% (15 degrees approximately) difference between preoperative and postoperative TIA (for an alpha of 0.05 and beta of 0.10) was calculated at 24 eyes. The Friedman test was used to compare TIC data between the follow up sessions. To identify presurgery factors able to predict postoperative TIA by calculating R2, we constructed a multivariate mixed linear stepwise regression model adjusted for patient eye cluster using Stata software v12.0 (Stata Corp, College Station, TX, USA). To identify these preoperative factors affecting angle width following ICL implant, all the baseline variables studied that could be associated with angle changes: TIA, age, sex, spherical error, ACD, axial length, IT500, WTW, IOL power, type (spherical/toric) and size, were introduced in the multivariate regression model. This stepwise model chose predictive variables by an automatic procedure: in each step, a variable is considered for addition to or subtraction from the set of explanatory variables based on some prespecified criterion (p when entered in the model <0.05). Significance was set at P< 0.05. RESULTS
The study sample was comprised of 54 eyes of 27 patients of mean age 31.2 ±5.1 years (range 22 to 44); 67% were women. The ICL V4c lenses implanted were spherical in 28 eyes and toric in 26 eyes. Implanted ICL showed a mean size of 13.2 ±0.3 mm (range 12.1 to 13.7), mean spherical power of -11.1 ±3.3 diopters (range -18 to -3.5) and mean cylinder of 1.3 ±1.4 (range 0 to 5). ACD was 3.23 ±0.28 mm (range 2.80 – 3.97), axial length was 26.6 ±1.8 mm (range 23.6 - 31.5) and WTW distance was 12.1 ±0.3 mm (11.4 - 12.7). IT500 was 434.4 4
ACCEPTED MANUSCRIPT ± 65.7 µm (246 – 633). The remaining baseline characteristics of the study population are provided in Table 1.
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The TIA and AOD500 values recorded at baseline and at the four follow-up times (1 month, 3 months, 1 year and 2 years) are provided in Table 2. The main difference detected in TIA was an angle narrowing between baseline and 1 month postsurgery of 39 to 41% with no preoperative differences between quadrants (P= .844, ANOVA). Values fell from 49.5 ±8.7, 48.3 ±9.6, and 49.1 ±8.6 degrees to 29.9 ±10.4, 28.4 ±10.8 and 28.8 ±9.1 degrees at one month in the nasal, temporal and inferior quadrants respectively, with no differences emerging between quadrants (P= .879, ANOVA). At 2 years postsurgery, no differences were observed in TIA over those produced at 1 month: 27.3 ±8.8 degrees (P= .133, GEE) in the nasal quadrant, 26.8 ±8.1 degrees (P= .376) in the temporal quadrant and 28.9 ±7 degrees in the inferior quadrant (P= 1.000). At this time point, differences in TIA were found between the temporal and inferior quadrants (adjusted p= .001), and between the nasal and inferior quadrants (adjusted p= .016).
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AOD500 fell from its presurgery values of 813.4 ±237.6, 845.1 ±305.4 and 836.2 ±36.4 µm for the nasal, temporal and inferior quadrants respectively (P= .764) to corresponding values of 384.2 ±156.8, 354.7 ±173.4, and 400.6 ±136.2 µm at 1 month and to similar values of 390.1 ±166.5, 354.1 ±151.9, and 402 ±125.3 µm at 2 years (P= 1.000). Throughout follow up, the temporal quadrant was significantly narrower than the inferior quadrant (P≤ .022).
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According to whether the ICL implanted was spherical or toric, differences were produced in preoperative TIA (52.4 ± 8.2 and 46.6 ± 8.3 degrees respectively; P= .006, t test), and in preoperative cylinder (-0.7 ± 0.5 and -2.4 ± 1.0 diopters respectively; P< .001) but not in spherical error (-9.3 ± 4.9 and -7.7 ± 2.8 diopters respectively; P= .106). In both these groups, TIA narrowing was similar at one month (mean 18.78 to 19.82 degrees; P= .677), whereas at 2 years, a greater narrowing effect was noted in the spherical lens group (26.7 ± 8 degrees versus 20.8 ± 7.1 degrees; P= .024). No case of lens rotation was observed during follow up.
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TIC was observed after ICL implant in 8 eyes of 8 patients (14.8%); at one month in 5 eyes and at 3 months in 3 additional eyes (Figure 4, Table 2). In these patients, presurgery TIA varied widely (34 to 54.4 degrees). In all cases TIC persisted at 2 years but no new cases were detected at 1 or 2 years of follow-up. In all 8 eyes, TIC only affected a single quadrant, mostly the temporal (7/8); the nasal quadrant being affected in 1 case. Mean TICL was 307 ± 288 µm at three months, 291 ±195 µm at one year and 225 ± 142 µm at two years (P= .159, Friedman). To identify preoperative factors affecting angle width following ICL implant, the baseline factors TIA, age, sex, spherical error, ACD, axial length, IT500, WTW, IOL power, type (spherical/toric) and size were introduced into a multivariate linear regression model. After elimination by the multivariate linear regression model of ACD, axial length, IOL power and type (because their p values were ≥0.05), the 7 remaining variables showed an adjusted R2= 0.915 for the 5
ACCEPTED MANUSCRIPT temporal quadrant, R2= 0.839 for the nasal quadrant and R2= 0.805 for the inferior quadrant (P< .001).
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The following equation was able to explain 91.5% of the variation in angle width at 2 years postimplant: two-year postimplant temporal TIA= 23.33 + 0.57 x preimplant TIA – 11.08 x sex (woman) – 0.87 x age – 0.402 x spherical error – 5.47 x IOL size – 0.038 x IT500 + 8.52 x WTW (Table 3). Accordingly, the factors returning the higher coefficients in the multivariate model for TIA at two years were sex, WTW and IOL size.
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Lens vault fell significantly from 589.7 ±279.8 µm (range 108 to 1240) at 1 month postsurgery to 458.3 ±258.4 µm (range 60 to 1220) at two years (P< .001). Correlations with this variable were observed for TIA of R=-0.483 to R=0.638 (P≤0.046) at 1 month postimplant and of R=-0.448 to R=-0.686 at 2 years (P< .001). A vault larger than 750 µm was observed in 12 eyes (23.1%) at 1 month postsurgery with TIA varying widely from 10 to 28.6 degrees, and in eight eyes (14.8%) at two years postsurgery with TIA varying from 13 to 32 degrees. In this subgroup of eyes, correlation between vault and TIA was R= -0.692 (P= .004) at one month and R=-0.514 (P= .129) at two years. No correlation was observed between IOP and TIA at 1 month, while this correlation was negative at 2 years. Similar correlations were detected between 1-month and 2-year postimplant TIA and preoperative TIA (R= 0.549 to 0.413; P< .001). Only weak correlation was noted between TIA and ACD or WTW (Table 4).
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On average, endothelial cell counts fell by 5.9% from presurgery to 2 years postimplant (mean 157.2 cells/mm2; 95%CI 91.0 – 223.3 cells/mm2; P< .001) (Table 1). Endothelial cell loss was not associated with TIA at 2 years (R= 0.192; P= .336), and neither was this factor related to the angles of patients who experienced most narrowing (≥ 30 degrees) following implant surgery (R= 0.089; P= .225).
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Among the complications observed, high IOP (45 mmHg) was noted at 1 month postsurgery (confirmed absent at 1 week postsurgery) in one eye. This high pressure was likely a response to the corticosteroid eye drops prescribed and was quickly resolved after postoperative treatment ceased. We also recorded mild anterior subcapsular cataract in one eye but BCVA remained stable (0.1 logMar) at 2 years so the lens was not explanted. DISCUSSION
The main findings of our FD-OCT study was angle narrowing recorded as mean TIA reductions of 39 - 41% and 41- 45% produced from presurgery to 1 month and 2 years post ICL implant respectively. In the presence of the ICL in the posterior chamber, the angle opening distance AOD500 was also reduced by 52% - 58% at both 1 month and 2 years postsurgery. In our previous study,22 narrowing of the angle shortly after lens implant (1 month) remained stable at 3 months, and no further significant narrowing was observed here at 2 years. However, we should consider that these lenses will have a mean life of 10 or 6
ACCEPTED MANUSCRIPT even 20 years, and we have yet to elucidate their long term consequences on the iridocorneal angle.
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Another factor to consider is that candidates for this type of phakic lens are usually highly myopic patients. These patients feature a wide preoperative TIA such that 2 years after surgery, the mean TIA in our series of patients was between 26 and 29 degrees. In another study by our group in the same outpatient setting,26 mean TIA in emmetropic subjects was 35 degrees, and 22 degrees in highly hyperopic individuals. This highlights that even when there is a fair amount of narrowing, angles are only slightly smaller than in emmetropes, and still wider than in hyperopes.
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In response to ICL placement, there have been several reports of angle narrowing such as that by Chung et al.19 who detected by UBM a 31.7% TIA reduction (from 38.1 ±8.7 to 26.0 ±6.5 degrees) and 41.4% AOD500 decrease (from 517.2 ±180.2 to 302.8 ±90.2 µm) one month after surgery. These authors also noted slight further TIA reductions at 6 months, 1 year and 2 years though differences were not significant. This observation is consistent with our results, though TIA means indicated slight narrowing at 2 years but the angle difference lacked significance. The similar AOD data reported by Chung's group at one month (302.8 ±90.2 µm) and 2 years of follow up (327.7 ±177.8 µm) are also in line with our findings.
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As we previously described,22 despite the horizontal placement of the ICL in the ciliary sulcus,25,27,28 angle narrowing was similar in the horizontal and inferior quadrants at one month (P= .143, ANOVA). This is because the lens is convex on its anterior side and could displace all 360 degrees of the iris in the pupil region through a tenting effect. Chung et al.19 described similar angle reductions across all four quadrants. At 2 years, we observed no differences in angle narrowing between the horizontal quadrants, but did so between the horizontal and inferior quadrants. We speculate that progressive horizontal narrowing of the TIA as opposed to the stability of AOD, could be attributable to the position of the ICL lens footplate just behind the angle recess.25
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In another UBM study by Lim et al.20 decreases were observed in TIA and AOD500 values after ICL V4b implantation of 28.4% and 27.3% respectively in subjects with a shallow anterior chamber. In agreement with our findings, these authors reported no further angle changes during follow up. Recently, Eissa et al.21 also described angle narrowing in response to ICL V4c placement from 40.1 ± 5.5 degrees presurgery to 25.3 ± 5.3 at 1 month and remaining stable at 18 months. These authors employed a Scheimpflug imaging instrument, whose resolution of angle structures is far worse than that of FD-OCT. In our study participants, 14.8% of the eyes showed TIC at 3 months post-ICL implant. Most often this contact only occurred in the temporal quadrant (87.5%), so we propose it could be related to the surgical incision. Because of the remaining open angles in the other quadrants, there was no angular block that could give rise to ocular hypertension. Remarkably, the length of this contact, or TICL,23 did not progress in these eyes (P= .159), and in some this length diminished (figure 4). Also, no late onset TIC was produced. Nonetheless, due 7
ACCEPTED MANUSCRIPT to the persistence of the TIC, patients need to be closely followed as it is well known that goniosynechiae could appear in the long run.
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Our adjusted multivariate linear regression model was able to explain 91.5% of the variation produced in TIA two years after ICL implant. The factors included in the model were known determinants of angle width such as preoperative TIA, sex, age, spherical error, and WTW. However, unlike the findings of our prior study, IOL size and iris thickness (IT500) emerged here as predictors of this variable. Thus, a greater IT500 was related to a narrower postoperative angle at 2 years. Interestingly, iris thickness was included in a model consisting of 6 variables to best predict angle width described in a population based study by Foo et al.29 Moreover, Wang et al. also observed that a thicker iris was a significant predictor of occludable angles in Caucasians.30
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In our study, visual outcomes for the ICL V4c were excellent as also reported by others.6,10,20 With regards to complications, a small lens vault (<250 µm) has been linked to an increased risk of cataract.11,14,15,20 We only observed one crystalline opacity in the 54 eyes during the 2 years of follow up. This eye had an angle of 12 degrees but the vault was 60 µm. Several studies have shown wide variation in the incidence of cataract after ICL V4c implant from 0.6% to 5.2%.6,11,14,15 However, in a study by Guber et al.24, the mean vault fell from 426 µm immediately postsurgery to 213 µm at 10 years of follow up, and 54.8% of patients developed cataract.
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No effects of ICL V4c implant were observed here on IOP. However, we did note moderate negative correlation between IOP and postoperative angle width at 2 years. Higueras et al.10 similarly detected no IOP modifications produced in response to the implant of ICL V4b and V4c. Remarkably, in the study by Guber et al. there was no significant increase in IOP until the tenth year of follow up.24
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We detected a 5.9% drop in endothelial cell numbers, though this loss was neither related to a narrowed angle nor to greater angle narrowing in response to implant surgery. This endothelial cell loss is comparable to that observed by others (1.7 - 9%).6
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Among the main limitations of our study is its short term follow up in relation to the mean lifetime of this lens, which could be between 10 and 20 years. In future studies, angle width modifications need to be assessed in the longer term. Also, we did not take measurements in the superior quadrant since this requires manipulation of the upper eyelid which could artifact the OCT images and neither can possible pigmentation effects be determined using this technique. It will also be interesting to examine angle changes produced after ICL placement in hyperopic patients. Indeed, these patients may be at a greater risk of angle closure and clinically relevant TIC. As far as we are aware, this study is the first to examine by FD-OCT, the angle effects of the implant of ICL V4c over 2 years of follow up. Our predictive model for postimplant iridocorneal angle could serve to avoid complications by carefully identifying suitable candidates for this type of surgery.
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In conclusion, our findings reveal considerable narrowing of the iridocorneal angle 1 month after ICL V4c implant, and no further narrowing at 2 years postimplant. Eight cases of trabecular-iris contact were attributed to surgery, but none had progressed at two years. We recommend the close follow up of these patients to check angle width and avoid longer term complications.
Acknowledgement section:
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a. Funding/support: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. b. Financial disclosures:
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JIFV, AMM, CFV, JAFV, LDPGL, CFP: No financial disclosures.
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JGF.: Financial support - Ivantis, Inc, (Irvine, CA); Transcend (Menlo Park, CA); Glaukos (Laguna Hills, CA); Innfocus (Miami, FL); Alcon (Fort Worth, TX).
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ACCEPTED MANUSCRIPT References 1. Sanders DR, Doney K, Poco M. United States Food and Drug Administration clinical trial of the implantable collamer lens (ICL) for moderate to high myopia: three-year follow-up. Ophthalmology 2004;111(9):1683–92.
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2. Sanders DR. Matched population comparison of the Visian implantable collamer lens and standard LASIK for myopia of -3.00 to -7.88 diopters. J Refract Surg 2007;23(6):537–53. 3. Huang D, Schallhorn SC, Sugar A, et al. Phakic intraocular lens implantation for the correction of myopia: a report by the American Academy of Ophthalmology. Ophthalmology 2009;116(11):2244–58.
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4. Jimenez-Alfaro I, Benitez del Castillo JM, Garcia-Feijoo J, et al. Safety of posterior chamber phakic intraocular lenses for the correction of high myopia: anterior segment changes after posterior chamber phakic intraocular lens implantation. Ophthalmology 2001;108(1):90–9.
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5. Igarashi A, Shimizu K, Kamiya K. Eight-year follow-up of posterior chamber phakic intraocular lens implantation for moderate to high myopia. Am J Ophthalmol 2014;157(3):532-9. 6. Packer M. Meta-analysis and review: effectiveness, safety, and central port design of the intraocular collamer lens. Clin Ophthalmol. 2016;10:1059-77.
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7. Huseynova T, Ozaki S, Ishizuka T, et al. Comparative study of 2 types of implantable collamer lenses, 1 with and 1 without a central artificial hole. Am J Ophthalmol 2014;157(6):1136-43. 8. Fernández-Vigo JI, Macarro-Merino A, Fernández-Francos J, et al. Computational study of aqueous humor dynamics assessing the vault and the pupil diameter in two posterior chamber phakic lenses. Invest Ophthalmol Vis Sci. 2016;57(11):4625-31.
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9. Fernandes P, Gonzalez-Meijome JM, Madrid-Costa D, et al. Implantable collamer posterior chamber intraocular lenses: a review of potential complications. J Refract Surg 2011;27(10):765-76. 10. Higueras-Esteban A, Ortiz-Gomariz A, Gutiérrez-Ortega R, et al. Intraocular pressure after implantation of the Visian Implantable Collamer Lens With CentraFLOW without iridotomy. Am J Ophthalmol 2013;156(4):800-5. 11. Alfonso JF, Lisa C, Fernández-Vega L, et al. Prevalence of cataract after collagen copolymer phakic intraocular lens implantation for myopia, hyperopia, and astigmatism. J Cataract Refract Surg 2015;41(4):800-5. 12. Schmidinger G, Lackner B, Pieh S, Skorpik C. Long-term changes in posterior chamber phakic intraocular collamer lens vaulting in myopic patients. Ophthalmology 2010;117(8):1506–11.
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ACCEPTED MANUSCRIPT 13. Lee H, Kang SY, Seo KY et al. Dynamic vaulting changes in V4c versus V4 posterior chamber phakic lenses under differing lighting conditions. Am J Ophthalmol 2014;158(6):1199-1204. 14. Maeng HS, Chung TY, Lee DH, Chung ES. Risk factor evaluation for cataract development in patients with low vaulting after phakic intraocular lens implantation. J Cataract Refract Surg 2011;37(5):881-5.
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15. Sanders DR. Anterior subcapsular opacities and cataracts 5 years after surgery in the Visian implantable collamer lens FDA trial. J Refract Surg 2008;24(6):566–70.
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16. García-Feijóo J, Hernández-Matamoros JL, Castillo-Gómez A, et al. Secondary glaucoma and severe endothelial damage after silicone phakic posterior chamber intraocular lens implantation. J Cataract Refract Surg 2004;30(8):1786-9.
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17. Abela-Formanek C, Kruger AJ, Dejaco-Ruhswurm I, et al. Gonioscopic changes after implantation of a posterior chamber lens in phakic myopic eyes. J Cataract Refract Surg 2001;27(12):1919-25. 18. Chun YS, Park IK, Lee HI, et al. Iris and trabecular meshwork pigment changes after posterior chamber phakic intraocular lens implantation. J Cataract Refract Surg 2006;32(9):1452–8.
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19. Chung TY, Park SC, Lee MO, et al. Changes in iridocorneal angle structure and trabecular pigmentation with STAAR implantable collamer lens during 2 years. J Refract Surg 2009;25(3):251–8. 20. Lim DH, Lee MG, Chung ES, Chung TY. Clinical results of posterior chamber phakic intraocular lens implantation in eyes with low anterior chamber depth. Am J Ophthalmol 2014;158(3):447-54.
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21. Eissa SA, Sadek SH, El-Deeb MW. Anterior Chamber Angle Evaluation following Phakic Posterior Chamber Collamer Lens with CentraFLOW and Its Correlation with ICL Vault and Intraocular Pressure. J Ophthalmol. 2016;2016:1383289.
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22. Fernández-Vigo JI, Macarro A, Fernández-Vigo C, et al. Effects of Implantable Collamer Lens V4c placement on iridocorneal angle measurements by Fourier domain optical coherence tomography. American Journal of Ophthalmology. 2016;162:43-52.e1. 23. Fernández-Vigo JI, De-Pablo-Gómez-De-Liaño L, Fernández-Vigo C, et al. Quantification of trabecular-iris contact and its prevalence by optical coherence tomography in a healthy Caucasian population. Eur J Ophthalmol. 2016;16:0. 24. Guber I, Mouvet V, Bergin C, et al. Clinical Outcomes and Cataract Formation Rates in Eyes 10 Years After Posterior Phakic Lens Implantation for Myopia. JAMA Ophthalmol. 2016. doi: 10.1001/jamaophthalmol.2016.0078.
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ACCEPTED MANUSCRIPT 25. Garcia-Feijóo J, Jimenez Alfaro I, Cuiña-Sardiña R, et al. Ultrasound biomicroscopy examination of posterior chamber phakic intraocular lens position. Ophthalmology 2003;110(1):163-72. 26. Fernández-Vigo JI, García-Feijóo J, Martínez-de-la-Casa JM, et al. Fourier domain optical coherence tomography to assess the iridocorneal angle and correlation study in a large Caucasian population. BMC Ophthalmol. 2016;18;16:42.
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27. Kojima T, Yokoyama S, Ito M, et al. Optimization of an implantable collamer lens sizing method using high-frequency ultrasound biomicroscopy. Am J Ophthalmol 2012;153(4):632-7.
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28. Alfonso JF, Fernández-Vega L, Lisa C, et al. Long-term evaluation of the central vault after phakic Collamer lens (ICL) implantation using OCT. Graefes Arch Clin Exp Ophthalmol 2012;250(12):1807-12.
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29. Foo LL, Nongpiur ME, Allen JC, et al. Determinants of angle width in Chinese Singaporeans. Ophthalmology. 2012;119(2):278-82.
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30. Wang YE, Li Y, Wang D, He M, Lin S. Comparison of factors associated with occludable angle between american Caucasians and ethnic Chinese. Invest Ophthalmol Vis Sci. 2013;54(12):7717-23.
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ACCEPTED MANUSCRIPT Figure captions: Figure 1. Implantable collamer lens position in the ciliary sulcus of the eye.
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Figure 2. Trabecular-iris angle measurements made by Fourier-domain optical coherence tomography before and after Visian implantable collamer lens V4c implantation. Upper row, baseline (left), and one month (middle left), three months (middle right) and two years (right) after surgery. Note that the narrowing produced after surgery (middle left) remained stable after two years (right). Lower row shows the angle measured as angle opening distance in another patient at the same time points (TIA= trabecular-iris angle measured by tracing a 500 µm line from the angle recess toward the Schwalbe's line and another line on the surface of the iris to the point crossing the first line. AOD= angle opening distance 500 µm from the scleral spur).
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Figure 3. Two examples of trabecular-iris contact (TIC) observed by Fourierdomain optical coherence tomography following Visian implantable collamer lens V4c implant. The first example (upper row: left=baseline, middle left= one month, middle= three months, middle right=one year, and right= two years after surgery) shows TIC (measured as trabecular-iris contact length, TICL) detected in a patient three months after surgery (middle). TIC diminished at one year and remained stable at two years of follow up. In the second example (lower row: left=baseline, middle left= one month, middle= three months, middle right=one year, and right= two years after surgery) TIC appeared at one month postimplant (middle left), and contact was most pronounced at 3 months (middle), diminishing at one year (middle right) and remaining stable at two years (right). It is possible to visualize the corneal incision made for surgical access.
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Figure 4. Anterior chamber angle assessed by Fourier-domain optical coherence tomography two years after Visian implantable collamer lens V4c implant. Angle closure associated with trabecular-iris contact was observed in the nasal quadrant (left) over the follow up period. However, the inferior (middle) and the temporal quadrants (right) remained open (TICL= trabecular-iris contact length; TIA= trabecular-iris angle).
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ACCEPTED MANUSCRIPT Preop.
1 month postop.
3 months postop.
1 year postop.
2 years postop.
Spherical error (D)
-8.48 ±4.03
0.10 ± 0.27
0.12 ±0.32
0.05 ±0.19
-0.02 ±0.44
(-21.0, -2.25)
(-0.50, 1)
(0, 1.5)
(0, 1)
(-0.5, 1)
-1.56 ±1.13
-0.30 ±0.58
-0.26 ±0.57
-0.10 ±0.39 (-1.75, 0)
-0.11 ± 0.37 (-1.5, 0)
(-5, 0)
(-2.25, 0)
(-1.75, 0)
1.45 ±0.27
0.05 ±0.09
0.05 ±0.11
0.02 ±0.11 (-0.1, 0.3)
0.02 ±0.10 (-0.1, 0.2)
(1, 1.7)
(-0.1, 0.4)
(-0.1, 0.3)
0.06 ±0.13
0.03 ±0.11
0.01 ±0.10
0.01 ± 0.09 (-0.2, 0.2)
0.01 ± 0.09 (-0.2, 0.2)
(-0.1, 0.4)
(-0.1, 0.3)
(-0.2, 0.2)
2637.9 ±255.6 (2097, 3268)
2609.5 ±241.1 (2063, 3084)
2596.9 ±217.1 (2083, 3026)
2568.3 ±227.9 (2056, 3045)
2480.8 ± 214.3 (2037, 2881)
16.6 ±3.0 (11, 21)
18.4 ±6.8 (9, 45)
Not applicable
589.7 ±279.8 (108, 1240)
BCVA (logMAR) ECC 2 (cells/mm ) IOP (mmHg) Lens vault (µm)
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UCVA (logMAR)
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Cylindrical error (D)
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Variable
15.5 ±2.7 (10, 21)
16.2 ±3.5 (8, 22)
15.5 ±2.5 (11, 21 )
557.5 ±276.7 (80, 1260)
505.6 ± 295.2 (51, 1270)
458.3 ± 258.4 (60, 1220)
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Table 1. Ocular variables recorded in the study population (54 eyes of 27 subjects) before, and 1 month, 3 months, 1 year and 2 years after ICL V4c implantation.
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D= diopters; UCVA= uncorrected visual acuity; BCVA= best-corrected visual acuity; logMAR= logarithm of the minimal angle of resolution; SD= standard deviation; ECC= endothelial cell count; IOP= intraocular pressure; µm= microns.
ACCEPTED MANUSCRIPT Table 2. Anterior chamber angle measurements made in the study population (54 eyes of 27 subjects) before, and 1 month, 3 months, 1 year and 2 years after ICL V4c implantation. Mean ± standard deviation, and range in parenthesis.
AOD500 nasal (µm)
1 year
2 years
P value
49.5 ±8.7
29.9 ±10.4
29.2 ±11.2
26.5 ± 8.8
27.3 ± 8.8
0.133
(27.4 – 67.7)
(10.2 – 55.9)
(0 – 57.9)
48.3 ±9.6
28.4 ±10.8
26.3 ±10.6
(23.3 – 66.3)
(5.4 – 53.4)
(5.7 – 46.5)
49.1 ±8.6
28.8 ±9.7
29.0 ±9.9
(31 – 63.8)
(13.4 – 49.5)
(12.7 – 52.3)
(11 – 40.3)
(12.2 – 39.9)
813.4 ± 237.6
384.2 ± 156.8
378.2 ± 169.9
376.3 ± 121.7
390.1 ± 166.5
(0 – 749)
(115 – 680)
(34 – 731 )
354.7 ± 173.4
335.4 ±163.2
354.1 ±151.9
(38 – 757)
(70 – 702)
328.6 ± 148.5
(120 – 697)
(397 – 1410)
AOD500 inferior (µm)
845.1 ± 305.4 (297 – 1260) 836.2 ± 236.4
400.6 ± 136.2
24.9 ± 9
26.8 ± 8.1
(4.2 – 41.8)
(5.3 – 40.8)
27.6 ± 6.5
28.9 ± 7
402 ± 125.3
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1.000
1.000
258 ± 203
307 ± 288
291 ± 195
225 ± 142
(81 – 588)
(85 – 843)
(98 – 529)
(77 – 495)
N= 8
N= 8
N= 8
1.000
(217 – 721)
TIA= trabecular-iris angle; AOD500= angle opening distance 500 microns from the scleral spur; TICL= Trabecular-iris contact length.
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1.000
(45 – 748)
(154 – 658)
N= 5
0.376
(41 – 680)
(117 – 906)
(188 – 761)
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Not applicable
(0 – 41.7)
387.3 ± 124.5
(453 – 1300) TICL (µm)
(0 – 41.4)
404.9 ± 154.2
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AOD500 temporal (µm)
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TIA inferior (degrees)
3 month postop
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TIA temporal (degrees)
1 month postop
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TIA nasal (degrees)
Preop
P value (level of significance): difference between 1 month and 2 years, adjusted with Generalized Estimating Equations.
0.159
ACCEPTED MANUSCRIPT Table 3: Multivariate analysis of variables affecting anterior chamber temporal angle 2 years after implantable collamer lens V4c implant in 54 eyes of 27 subjects B
95% CI
P value
Constant
23.33
-21.45, 68.11
.273
TIA preop. (degrees)
0.57
0.36, 0.78
.000
Age (years)
-0.874
-1.21, -0.53
Sex (female)
-11.07
-16.55, -5.59
Spherical error (diopters)
-0.40
-0.74, -0.06
Iris thickness (IT500) (µm)
-0.038
-0.06, -0.01
White-to-white distance (mm)
8.52
IOL size (mm)
-5.46
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Variable
.000
.001
.026
.007
5.23, 11.81
.000
-10.92, -0.01
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Multivariate linear stepwise regression model used to determine factors affecting postoperative TIA.
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TIA= trabecular-iris angle; ACD= anterior chamber depth; iris thickness (IT500) at the perpendicular point 500 µm to the scleral spur; IOL= Intraocular lens; 95% CI= confidence interval at 95%; B= unstandardized coefficient.
ACCEPTED MANUSCRIPT IOP
TIA preop.
ACD preop.
WTW preop.
TIA nasal 1 month postop.
-0.483 (p= .001)
0.060 (p= .500)
0.525 (p= .000)
0.229 (p= .240)
-0.041 (p= .750)
TIA temporal 1 month postop.
-0.535 (p= .001)
0.096 (p= .359)
0.437 (p= .001)
0.053 (p= .742)
-0.036 (p= .734)
TIA inferior 1 month postop.
-0.638 (p= .001)
0.002 (p= .399)
0.413 (p= .000)
0.047 (p= .719)
-0.130 (p= .238)
AOD500 nasal 1 month postop.
-0.493(p= .001)
0.126 (p= .699)
0.489 (p= .000)
0.169 (p= .346)
-0.122 (p= .426)
AOD500 temporal 1 month postop.
-0.554 (p= .001)
0.142 (p= .189)
0.437 (p= .000)
0.101 (p= .595)
-0.037 (p= .809)
AOD500 inferior 1 month postop.
-0.612 (p= .001)
-0.092 (p= .511)
0.422 (p= .000)
0.102 (p= .408)
-0.070 (p= .566)
TIA nasal 2 years postop.
-0.448 (p= .001)
-0.342 (p= .050)
0.549 (p= .000)
0.218 (p= .119)
-0.170 (p= .456)
TIA temporal 2 years postop.
-0.609 (p= .000)
-0.258 (p= .137)
0.499 (p= .000)
0.230 (p= .189)
-0.202 (p= .362)
TIA inferior 2 years postop.
-0.686 (p= .001)
-0.336 (p= .131)
0.528 (p= .000)
0.082 (p= .688)
-0.004 (p= .984)
AOD500 nasal 2 years postop.
-0.509 (p= .001)
-0.431 (p= .006)
0.526 (p= .000)
0.202 (p= .277)
-0.125 (p= .567)
AOD500 temporal 2 years postop.
-0.531 (p= .003)
-0.328 (p= .043)
0.462 (p= .002)
0.283 (p= .164)
-0.242 (p= .315)
AOD500 inferior 2 years postop.
-0.6037 (p= .001)
-0.349 (p= .110)
0.469 (p= .000)
0.084 (p= .609)
-0.014 (p= .932)
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Lens vault
a
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Table 4. Correlations between angle measurements and the ocular factors examined in the study population. Pearson correlation (R) was used for trabecular-iris angle (TIA), correcting for patient cluster. For the non-normally distributed AOD500 data, Spearman’s Rho was used. b
Lens vault= distance from posterior ICL surface to anterior crystalline lens surface; IOP= intraocular pressure; ACD= anterior chamber depth; WTW= white to white distance; TIA= trabecular-iris angle; AOD500= angle opening distance 500 microns from the scleral spur. c
Lens vault and IOP measurements were compared at one-month and threemonths of follow up as the time when the angle measurements were made. 1
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S0002-9394(17)30263-5
DOI:
10.1016/j.ajo.2017.06.018
Reference:
AJOPHT 10176
To appear in:
American Journal of Ophthalmology
Received Date: 6 April 2017 Revised Date:
14 June 2017
Accepted Date: 19 June 2017
Please cite this article as: Fernández-Vigo JI, Macarro-Merino A, Fernández-Vigo C, Fernández-Vigo JÁ, De-Pablo-Gómez-de-Liaño L, Fernández-Pérez C, García-Feijóo J, Impacts of implantable collamer lens V4c placement on angle measurements made by optical coherence tomography: two-year follow up, American Journal of Ophthalmology (2017), doi: 10.1016/j.ajo.2017.06.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT ABSTRACT Purpose: To determine iridocorneal angle changes produced after two years of implantable collamer lens® (ICL) V4c (STAAR Surgical AG) placement by Fourier-domain optical coherence tomography (FD-OCT). Design: Prospective interventional case series.
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Methods: In 54 eyes of 27 myopic subjects FD-OCT (RTVue®, Optovue Inc.) iridocorneal angle measurements were made before, and 1 month, 3 months, 1 year and 2 years after ICL implant. Trabecular-iris angle (TIA), angle opening distance 500 µm from the scleral spur (AOD500) and iridotrabecular contact length (TICL) were compared among these time points and the quadrants nasal, temporal and inferior.
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Results: Preoperative TIAs were 49.5 ±8.7, 48.3 ±9.6, and 49.1 ±8.6 degrees for the nasal, temporal and inferior quadrants (P<.001). Corresponding values were 29.9 ±10.4, 28.4 ±10.8 and 28.8 ±9.7 degrees at 1 month and 27.3 ±8.8, 26.8 ±8.1 and 28.9 ±7 degrees at 2 years of follow-up indicating angle narrowing of 39 to 45% and no further narrowing beyond 1 month in the nasal (P= .133), temporal (P= .376) and inferior (P= 1.000) quadrants. Trabecular-iris contact (TIC) was observed in 8 eyes of 8 subjects mostly only in the temporal quadrant. Mean TICL failed to vary during follow-up (307 ±288 µm at 3 months and 225 ±142 µm at 2 years, p= .159).
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Conclusions: In response to ICL V4c implant, considerable angle narrowing was detected at 1 month but this narrowing remained stable at 2 years. In the 8 cases of TIC, no progression of contact was observed beyond 3 months postimplant.
ACCEPTED MANUSCRIPT Title: Impacts of implantable collamer lens V4c placement on angle measurements made by optical coherence tomography: two-year follow up
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Authors: José Ignacio Fernández-Vigo,1,2 Ana Macarro-Merino,2 Cristina Fernández-Vigo,2 José Ángel Fernández-Vigo,2,3 Lucía De-Pablo-Gómez-deLiaño,2 Cristina Fernández-Pérez,4 Julián García-Feijóo.1
1. Department of Ophthalmology, Hospital Clínico San Carlos and Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain. 2. Centro Internacional de Oftalmología Avanzada, Madrid, Spain.
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3. Department of Ophthalmology, Universidad de Extremadura, Badajoz, Spain.
Corresponding author: José Ignacio Fernández-Vigo
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4. Department of Preventive Medicine, Hospital Clínico San Carlos and Instituto de Investigación sanitaria (IdISSC), Madrid, Spain.
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Centro Internacional de Oftalmología Avanzada c/Zurbano 71, 28010 Madrid, Spain email: [email protected]
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Short title: Two-year OCT angle changes after implantable collamer lens Financial support: None
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The authors declare no conflicts of interest
1
ACCEPTED MANUSCRIPT INTRODUCTION For the treatment of myopia, hyperopia and astigmatism, the phakic Visian implantable collamer lens® (ICL, STAAR Surgical AG) is rapidly gaining popularity. This option has several benefits over keratorefractive procedures including rapid visual recovery, and a better and more stable visual outcome.1-6
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ICL was designed as a precrystalline posterior chamber lens. The latest model V4c has a central hole or AquaPORT® to facilitate aqueous humor outflow and thus avoid the need for iridotomy.7-8 However, this new ICL model still has several drawbacks common to all posterior chamber lenses, and may induce complications such as raised intraocular pressure (IOP), pigment dispersion, abnormal pupil dynamics, cataract or endothelial abnormalities.6,9-11 There are two main concerns about posterior chamber lenses related to the final vault distance between the posterior ICL surface and the anterior crystalline surface.12-13 When this distance is insufficient, the risk of developing cataract is increased,11,14,15 while if there is excessive distance, angle closure, or pupillary block, is induced, possibly leading to glaucoma.16
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To date, only a few studies have examined anterior chamber angle modifications produced in response to ICL implantation. Early research efforts were based on gonioscopy examination17,18 with its shortcomings of subjectivity and patient discomfort. This was followed by studies based on ultrasound biomicroscopy (UBM) in which angle narrowing was observed by Chung et al.19 and, in patients with a shallow anterior chamber, by Lim et al.20 More recently, angle narrowing has been observed using a Scheimpflug device in response to the V4c ICL model.21 However, optical coherence tomography (OCT) offers improved resolution over both the UBM and Scheimpflug-based techniques.
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METHODS
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In a prior study,22 using Fourier-domain OCT (FD-OCT) we determined angle changes produced 3 months after ICL (V4c) implant. Given the results of this study clearly indicated angle narrowing, the present study sought to determine whether this narrowing would continue beyond this time point and to identify factors predictive of postimplant angle closure. A further objective was to follow patients who developed trabecular-iris contact (TIC) soon after implant surgery.
For this prospective interventional case series study, we recruited 27 patients (54 eyes) consecutively scheduled for ICL implant to treat myopia over the period June 2013 to February 2015 at the Centro Internacional de Oftalmología Avanzada, Madrid (Spain). Of these 27 patients, 19 were participants of our previous 3-month study.22 The study protocol adhered to the tenets of the Declaration of Helsinki and received IRB approval prospectively from the University of Extremadura (Badajoz, Spain). This observational study was registered in www.clinicaltrials.gov. Before implant surgery, written informed consent was obtained from each participant. Inclusion criteria were an age between 20 and 45 years, and a stable refractive state over the last 2 years. Subjects were excluded if they had an anterior 2
ACCEPTED MANUSCRIPT chamber depth < 2.8 mm, an endothelial cell count <2000 cells/mm2, hyperopia, a history of glaucoma or of ocular inflammation, or preexisting corneal disease.
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Examination procedures
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The characteristics of the V4c model ICLs implanted in these myopic patients have been described in our previous study.22 In each participant, the ICL was aligned with the 180º meridian and rotated a maximum of 5-10º (Figure 1). Lens rotation was assessed after pupil dilatation by biomicroscopy. All lens implant operations were conducted by the same surgeon (AMM). The surgical technique consists of a corneal paracentesis and intracamerular lidocaine 1%. The anterior chamber is filled with a hydroxypropyl methylcellulose solution as viscoelastic (OcuCoat, Bausch & Lomb, Rochester, New York, USA). Then, through a 3.2 mm clear corneal temporal incision, the ICL is inserted with an injector (STAAR Surgical Co.) and correctly positioned with the help of a hook. Once remnants of viscoelastic have been removed with saline, 1 mg of cefuroxime sodium is injected and incisions are hydrated to complete the surgical procedure. Postoperative treatment was 4 drops per day of moxifloxacin for 7 days and tobramycin and dexamethasone 0.1% 4 times daily and tapered over 30 days.
All patients underwent a standard examination before surgery consisting of general medical history, visual acuity, anterior slit-lamp biomicroscopy, posterior segment ophthalmoscopy, tonometry (Goldmann), and endothelial cell count (Tomey®, Nagoya, Japan).
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Pentacam® was used to measure anterior chamber depth (ACD) from the endothelium (Oculus Inc., Wetzlar, Germany). Axial length, white-to-white (WTW) distance and pupil diameter were measured using the IOL Master® (Carl Zeiss, Meditec, Dublin, CA, USA).
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Visual outcome was assessed by measuring uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) using the logMAR scale. After implant surgery, follow-up visits were conducted at 1 and 3 months, and 1 and 2 years. In each postsurgery visit, the following were recorded: UCVA, BCVA, refractive error, IOP, lens vault, endothelial cell count and FD-OCT iridocorneal angle measurements. Fourier-domain optical coherence tomography For iridocorneal angle measurements, we used RTVue® 100 (Optovue Inc., Fremont, CA, USA). This instrument has an 840 nm laser diode; scan speed is 26.000 A-scans per second, and axial resolution is 5 - 8 µm. Exams were performed with the CAM-L lens on the nasal, temporal and inferior quadrants (3, 6 and 9 o’clock) under mesopic conditions with the device’s software set to Angle mode. The area captured was 3 x 2.3 mm centered at the limbus. Images were obtained by a trained examiner (JIFV) with the patient looking at a fixed point inside the device. Each quadrant was scanned three times and the image showing the best quality and least noise selected for subsequent angle measurements. 3
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The measurements made were: trabecular-iris angle (TIA), tracing a 500 µm line from the angle recess toward the Schwalbe's line and another line on the surface of the iris to the point crossing the first line (Figure 2, upper row); angle opening distance 500 µm from the scleral spur (AOD500) as the distance at right angles from the trabecular meshwork 500 µm anteriorly from the scleral spur to the anterior iris surface (Figure 2, inferior row); iris thickness (IT500) at the perpendicular point 500 µm to the scleral spur (Figure 2, inferior row left); and trabecular-iris contact length (TICL) as the linear distance of contact between the trabecular meshwork and the iris (Figure 3 and 4).23 Only narrow angles show TIC such that TICL can only be measured in eyes with this characteristic feature. The vault was also measured manually in the FD-OCT images by tracing a line from the center of the anterior pole of the crystalline lens to the posterior pole of the ICL.
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Statistical analysis
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Statistical tests were performed using the software package SPSS® (Statistical Package for the Social Sciences, v18.0; SPSS Inc., Chicago, IL). Univariate correlations were identified through Pearson's correlation test, or Spearman’s Rho test in the case of non-normally distributed data (spherical error and AOD500). Generalized estimating equations were employed to control for intereye correlation, assessing postsurgery differences in measurements between follow-up sessions. Presurgery differences in angle measurements between quadrants were determined by ANOVA with Bonferroni correction. The sample size needed to detect a 30% (15 degrees approximately) difference between preoperative and postoperative TIA (for an alpha of 0.05 and beta of 0.10) was calculated at 24 eyes. The Friedman test was used to compare TIC data between the follow up sessions. To identify presurgery factors able to predict postoperative TIA by calculating R2, we constructed a multivariate mixed linear stepwise regression model adjusted for patient eye cluster using Stata software v12.0 (Stata Corp, College Station, TX, USA). To identify these preoperative factors affecting angle width following ICL implant, all the baseline variables studied that could be associated with angle changes: TIA, age, sex, spherical error, ACD, axial length, IT500, WTW, IOL power, type (spherical/toric) and size, were introduced in the multivariate regression model. This stepwise model chose predictive variables by an automatic procedure: in each step, a variable is considered for addition to or subtraction from the set of explanatory variables based on some prespecified criterion (p when entered in the model <0.05). Significance was set at P< 0.05. RESULTS
The study sample was comprised of 54 eyes of 27 patients of mean age 31.2 ±5.1 years (range 22 to 44); 67% were women. The ICL V4c lenses implanted were spherical in 28 eyes and toric in 26 eyes. Implanted ICL showed a mean size of 13.2 ±0.3 mm (range 12.1 to 13.7), mean spherical power of -11.1 ±3.3 diopters (range -18 to -3.5) and mean cylinder of 1.3 ±1.4 (range 0 to 5). ACD was 3.23 ±0.28 mm (range 2.80 – 3.97), axial length was 26.6 ±1.8 mm (range 23.6 - 31.5) and WTW distance was 12.1 ±0.3 mm (11.4 - 12.7). IT500 was 434.4 4
ACCEPTED MANUSCRIPT ± 65.7 µm (246 – 633). The remaining baseline characteristics of the study population are provided in Table 1.
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The TIA and AOD500 values recorded at baseline and at the four follow-up times (1 month, 3 months, 1 year and 2 years) are provided in Table 2. The main difference detected in TIA was an angle narrowing between baseline and 1 month postsurgery of 39 to 41% with no preoperative differences between quadrants (P= .844, ANOVA). Values fell from 49.5 ±8.7, 48.3 ±9.6, and 49.1 ±8.6 degrees to 29.9 ±10.4, 28.4 ±10.8 and 28.8 ±9.1 degrees at one month in the nasal, temporal and inferior quadrants respectively, with no differences emerging between quadrants (P= .879, ANOVA). At 2 years postsurgery, no differences were observed in TIA over those produced at 1 month: 27.3 ±8.8 degrees (P= .133, GEE) in the nasal quadrant, 26.8 ±8.1 degrees (P= .376) in the temporal quadrant and 28.9 ±7 degrees in the inferior quadrant (P= 1.000). At this time point, differences in TIA were found between the temporal and inferior quadrants (adjusted p= .001), and between the nasal and inferior quadrants (adjusted p= .016).
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AOD500 fell from its presurgery values of 813.4 ±237.6, 845.1 ±305.4 and 836.2 ±36.4 µm for the nasal, temporal and inferior quadrants respectively (P= .764) to corresponding values of 384.2 ±156.8, 354.7 ±173.4, and 400.6 ±136.2 µm at 1 month and to similar values of 390.1 ±166.5, 354.1 ±151.9, and 402 ±125.3 µm at 2 years (P= 1.000). Throughout follow up, the temporal quadrant was significantly narrower than the inferior quadrant (P≤ .022).
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According to whether the ICL implanted was spherical or toric, differences were produced in preoperative TIA (52.4 ± 8.2 and 46.6 ± 8.3 degrees respectively; P= .006, t test), and in preoperative cylinder (-0.7 ± 0.5 and -2.4 ± 1.0 diopters respectively; P< .001) but not in spherical error (-9.3 ± 4.9 and -7.7 ± 2.8 diopters respectively; P= .106). In both these groups, TIA narrowing was similar at one month (mean 18.78 to 19.82 degrees; P= .677), whereas at 2 years, a greater narrowing effect was noted in the spherical lens group (26.7 ± 8 degrees versus 20.8 ± 7.1 degrees; P= .024). No case of lens rotation was observed during follow up.
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TIC was observed after ICL implant in 8 eyes of 8 patients (14.8%); at one month in 5 eyes and at 3 months in 3 additional eyes (Figure 4, Table 2). In these patients, presurgery TIA varied widely (34 to 54.4 degrees). In all cases TIC persisted at 2 years but no new cases were detected at 1 or 2 years of follow-up. In all 8 eyes, TIC only affected a single quadrant, mostly the temporal (7/8); the nasal quadrant being affected in 1 case. Mean TICL was 307 ± 288 µm at three months, 291 ±195 µm at one year and 225 ± 142 µm at two years (P= .159, Friedman). To identify preoperative factors affecting angle width following ICL implant, the baseline factors TIA, age, sex, spherical error, ACD, axial length, IT500, WTW, IOL power, type (spherical/toric) and size were introduced into a multivariate linear regression model. After elimination by the multivariate linear regression model of ACD, axial length, IOL power and type (because their p values were ≥0.05), the 7 remaining variables showed an adjusted R2= 0.915 for the 5
ACCEPTED MANUSCRIPT temporal quadrant, R2= 0.839 for the nasal quadrant and R2= 0.805 for the inferior quadrant (P< .001).
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The following equation was able to explain 91.5% of the variation in angle width at 2 years postimplant: two-year postimplant temporal TIA= 23.33 + 0.57 x preimplant TIA – 11.08 x sex (woman) – 0.87 x age – 0.402 x spherical error – 5.47 x IOL size – 0.038 x IT500 + 8.52 x WTW (Table 3). Accordingly, the factors returning the higher coefficients in the multivariate model for TIA at two years were sex, WTW and IOL size.
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Lens vault fell significantly from 589.7 ±279.8 µm (range 108 to 1240) at 1 month postsurgery to 458.3 ±258.4 µm (range 60 to 1220) at two years (P< .001). Correlations with this variable were observed for TIA of R=-0.483 to R=0.638 (P≤0.046) at 1 month postimplant and of R=-0.448 to R=-0.686 at 2 years (P< .001). A vault larger than 750 µm was observed in 12 eyes (23.1%) at 1 month postsurgery with TIA varying widely from 10 to 28.6 degrees, and in eight eyes (14.8%) at two years postsurgery with TIA varying from 13 to 32 degrees. In this subgroup of eyes, correlation between vault and TIA was R= -0.692 (P= .004) at one month and R=-0.514 (P= .129) at two years. No correlation was observed between IOP and TIA at 1 month, while this correlation was negative at 2 years. Similar correlations were detected between 1-month and 2-year postimplant TIA and preoperative TIA (R= 0.549 to 0.413; P< .001). Only weak correlation was noted between TIA and ACD or WTW (Table 4).
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On average, endothelial cell counts fell by 5.9% from presurgery to 2 years postimplant (mean 157.2 cells/mm2; 95%CI 91.0 – 223.3 cells/mm2; P< .001) (Table 1). Endothelial cell loss was not associated with TIA at 2 years (R= 0.192; P= .336), and neither was this factor related to the angles of patients who experienced most narrowing (≥ 30 degrees) following implant surgery (R= 0.089; P= .225).
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Among the complications observed, high IOP (45 mmHg) was noted at 1 month postsurgery (confirmed absent at 1 week postsurgery) in one eye. This high pressure was likely a response to the corticosteroid eye drops prescribed and was quickly resolved after postoperative treatment ceased. We also recorded mild anterior subcapsular cataract in one eye but BCVA remained stable (0.1 logMar) at 2 years so the lens was not explanted. DISCUSSION
The main findings of our FD-OCT study was angle narrowing recorded as mean TIA reductions of 39 - 41% and 41- 45% produced from presurgery to 1 month and 2 years post ICL implant respectively. In the presence of the ICL in the posterior chamber, the angle opening distance AOD500 was also reduced by 52% - 58% at both 1 month and 2 years postsurgery. In our previous study,22 narrowing of the angle shortly after lens implant (1 month) remained stable at 3 months, and no further significant narrowing was observed here at 2 years. However, we should consider that these lenses will have a mean life of 10 or 6
ACCEPTED MANUSCRIPT even 20 years, and we have yet to elucidate their long term consequences on the iridocorneal angle.
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Another factor to consider is that candidates for this type of phakic lens are usually highly myopic patients. These patients feature a wide preoperative TIA such that 2 years after surgery, the mean TIA in our series of patients was between 26 and 29 degrees. In another study by our group in the same outpatient setting,26 mean TIA in emmetropic subjects was 35 degrees, and 22 degrees in highly hyperopic individuals. This highlights that even when there is a fair amount of narrowing, angles are only slightly smaller than in emmetropes, and still wider than in hyperopes.
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In response to ICL placement, there have been several reports of angle narrowing such as that by Chung et al.19 who detected by UBM a 31.7% TIA reduction (from 38.1 ±8.7 to 26.0 ±6.5 degrees) and 41.4% AOD500 decrease (from 517.2 ±180.2 to 302.8 ±90.2 µm) one month after surgery. These authors also noted slight further TIA reductions at 6 months, 1 year and 2 years though differences were not significant. This observation is consistent with our results, though TIA means indicated slight narrowing at 2 years but the angle difference lacked significance. The similar AOD data reported by Chung's group at one month (302.8 ±90.2 µm) and 2 years of follow up (327.7 ±177.8 µm) are also in line with our findings.
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As we previously described,22 despite the horizontal placement of the ICL in the ciliary sulcus,25,27,28 angle narrowing was similar in the horizontal and inferior quadrants at one month (P= .143, ANOVA). This is because the lens is convex on its anterior side and could displace all 360 degrees of the iris in the pupil region through a tenting effect. Chung et al.19 described similar angle reductions across all four quadrants. At 2 years, we observed no differences in angle narrowing between the horizontal quadrants, but did so between the horizontal and inferior quadrants. We speculate that progressive horizontal narrowing of the TIA as opposed to the stability of AOD, could be attributable to the position of the ICL lens footplate just behind the angle recess.25
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In another UBM study by Lim et al.20 decreases were observed in TIA and AOD500 values after ICL V4b implantation of 28.4% and 27.3% respectively in subjects with a shallow anterior chamber. In agreement with our findings, these authors reported no further angle changes during follow up. Recently, Eissa et al.21 also described angle narrowing in response to ICL V4c placement from 40.1 ± 5.5 degrees presurgery to 25.3 ± 5.3 at 1 month and remaining stable at 18 months. These authors employed a Scheimpflug imaging instrument, whose resolution of angle structures is far worse than that of FD-OCT. In our study participants, 14.8% of the eyes showed TIC at 3 months post-ICL implant. Most often this contact only occurred in the temporal quadrant (87.5%), so we propose it could be related to the surgical incision. Because of the remaining open angles in the other quadrants, there was no angular block that could give rise to ocular hypertension. Remarkably, the length of this contact, or TICL,23 did not progress in these eyes (P= .159), and in some this length diminished (figure 4). Also, no late onset TIC was produced. Nonetheless, due 7
ACCEPTED MANUSCRIPT to the persistence of the TIC, patients need to be closely followed as it is well known that goniosynechiae could appear in the long run.
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Our adjusted multivariate linear regression model was able to explain 91.5% of the variation produced in TIA two years after ICL implant. The factors included in the model were known determinants of angle width such as preoperative TIA, sex, age, spherical error, and WTW. However, unlike the findings of our prior study, IOL size and iris thickness (IT500) emerged here as predictors of this variable. Thus, a greater IT500 was related to a narrower postoperative angle at 2 years. Interestingly, iris thickness was included in a model consisting of 6 variables to best predict angle width described in a population based study by Foo et al.29 Moreover, Wang et al. also observed that a thicker iris was a significant predictor of occludable angles in Caucasians.30
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In our study, visual outcomes for the ICL V4c were excellent as also reported by others.6,10,20 With regards to complications, a small lens vault (<250 µm) has been linked to an increased risk of cataract.11,14,15,20 We only observed one crystalline opacity in the 54 eyes during the 2 years of follow up. This eye had an angle of 12 degrees but the vault was 60 µm. Several studies have shown wide variation in the incidence of cataract after ICL V4c implant from 0.6% to 5.2%.6,11,14,15 However, in a study by Guber et al.24, the mean vault fell from 426 µm immediately postsurgery to 213 µm at 10 years of follow up, and 54.8% of patients developed cataract.
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No effects of ICL V4c implant were observed here on IOP. However, we did note moderate negative correlation between IOP and postoperative angle width at 2 years. Higueras et al.10 similarly detected no IOP modifications produced in response to the implant of ICL V4b and V4c. Remarkably, in the study by Guber et al. there was no significant increase in IOP until the tenth year of follow up.24
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We detected a 5.9% drop in endothelial cell numbers, though this loss was neither related to a narrowed angle nor to greater angle narrowing in response to implant surgery. This endothelial cell loss is comparable to that observed by others (1.7 - 9%).6
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Among the main limitations of our study is its short term follow up in relation to the mean lifetime of this lens, which could be between 10 and 20 years. In future studies, angle width modifications need to be assessed in the longer term. Also, we did not take measurements in the superior quadrant since this requires manipulation of the upper eyelid which could artifact the OCT images and neither can possible pigmentation effects be determined using this technique. It will also be interesting to examine angle changes produced after ICL placement in hyperopic patients. Indeed, these patients may be at a greater risk of angle closure and clinically relevant TIC. As far as we are aware, this study is the first to examine by FD-OCT, the angle effects of the implant of ICL V4c over 2 years of follow up. Our predictive model for postimplant iridocorneal angle could serve to avoid complications by carefully identifying suitable candidates for this type of surgery.
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In conclusion, our findings reveal considerable narrowing of the iridocorneal angle 1 month after ICL V4c implant, and no further narrowing at 2 years postimplant. Eight cases of trabecular-iris contact were attributed to surgery, but none had progressed at two years. We recommend the close follow up of these patients to check angle width and avoid longer term complications.
Acknowledgement section:
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a. Funding/support: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. b. Financial disclosures:
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JIFV, AMM, CFV, JAFV, LDPGL, CFP: No financial disclosures.
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JGF.: Financial support - Ivantis, Inc, (Irvine, CA); Transcend (Menlo Park, CA); Glaukos (Laguna Hills, CA); Innfocus (Miami, FL); Alcon (Fort Worth, TX).
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ACCEPTED MANUSCRIPT References 1. Sanders DR, Doney K, Poco M. United States Food and Drug Administration clinical trial of the implantable collamer lens (ICL) for moderate to high myopia: three-year follow-up. Ophthalmology 2004;111(9):1683–92.
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2. Sanders DR. Matched population comparison of the Visian implantable collamer lens and standard LASIK for myopia of -3.00 to -7.88 diopters. J Refract Surg 2007;23(6):537–53. 3. Huang D, Schallhorn SC, Sugar A, et al. Phakic intraocular lens implantation for the correction of myopia: a report by the American Academy of Ophthalmology. Ophthalmology 2009;116(11):2244–58.
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4. Jimenez-Alfaro I, Benitez del Castillo JM, Garcia-Feijoo J, et al. Safety of posterior chamber phakic intraocular lenses for the correction of high myopia: anterior segment changes after posterior chamber phakic intraocular lens implantation. Ophthalmology 2001;108(1):90–9.
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5. Igarashi A, Shimizu K, Kamiya K. Eight-year follow-up of posterior chamber phakic intraocular lens implantation for moderate to high myopia. Am J Ophthalmol 2014;157(3):532-9. 6. Packer M. Meta-analysis and review: effectiveness, safety, and central port design of the intraocular collamer lens. Clin Ophthalmol. 2016;10:1059-77.
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7. Huseynova T, Ozaki S, Ishizuka T, et al. Comparative study of 2 types of implantable collamer lenses, 1 with and 1 without a central artificial hole. Am J Ophthalmol 2014;157(6):1136-43. 8. Fernández-Vigo JI, Macarro-Merino A, Fernández-Francos J, et al. Computational study of aqueous humor dynamics assessing the vault and the pupil diameter in two posterior chamber phakic lenses. Invest Ophthalmol Vis Sci. 2016;57(11):4625-31.
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9. Fernandes P, Gonzalez-Meijome JM, Madrid-Costa D, et al. Implantable collamer posterior chamber intraocular lenses: a review of potential complications. J Refract Surg 2011;27(10):765-76. 10. Higueras-Esteban A, Ortiz-Gomariz A, Gutiérrez-Ortega R, et al. Intraocular pressure after implantation of the Visian Implantable Collamer Lens With CentraFLOW without iridotomy. Am J Ophthalmol 2013;156(4):800-5. 11. Alfonso JF, Lisa C, Fernández-Vega L, et al. Prevalence of cataract after collagen copolymer phakic intraocular lens implantation for myopia, hyperopia, and astigmatism. J Cataract Refract Surg 2015;41(4):800-5. 12. Schmidinger G, Lackner B, Pieh S, Skorpik C. Long-term changes in posterior chamber phakic intraocular collamer lens vaulting in myopic patients. Ophthalmology 2010;117(8):1506–11.
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ACCEPTED MANUSCRIPT 13. Lee H, Kang SY, Seo KY et al. Dynamic vaulting changes in V4c versus V4 posterior chamber phakic lenses under differing lighting conditions. Am J Ophthalmol 2014;158(6):1199-1204. 14. Maeng HS, Chung TY, Lee DH, Chung ES. Risk factor evaluation for cataract development in patients with low vaulting after phakic intraocular lens implantation. J Cataract Refract Surg 2011;37(5):881-5.
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15. Sanders DR. Anterior subcapsular opacities and cataracts 5 years after surgery in the Visian implantable collamer lens FDA trial. J Refract Surg 2008;24(6):566–70.
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16. García-Feijóo J, Hernández-Matamoros JL, Castillo-Gómez A, et al. Secondary glaucoma and severe endothelial damage after silicone phakic posterior chamber intraocular lens implantation. J Cataract Refract Surg 2004;30(8):1786-9.
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17. Abela-Formanek C, Kruger AJ, Dejaco-Ruhswurm I, et al. Gonioscopic changes after implantation of a posterior chamber lens in phakic myopic eyes. J Cataract Refract Surg 2001;27(12):1919-25. 18. Chun YS, Park IK, Lee HI, et al. Iris and trabecular meshwork pigment changes after posterior chamber phakic intraocular lens implantation. J Cataract Refract Surg 2006;32(9):1452–8.
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19. Chung TY, Park SC, Lee MO, et al. Changes in iridocorneal angle structure and trabecular pigmentation with STAAR implantable collamer lens during 2 years. J Refract Surg 2009;25(3):251–8. 20. Lim DH, Lee MG, Chung ES, Chung TY. Clinical results of posterior chamber phakic intraocular lens implantation in eyes with low anterior chamber depth. Am J Ophthalmol 2014;158(3):447-54.
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21. Eissa SA, Sadek SH, El-Deeb MW. Anterior Chamber Angle Evaluation following Phakic Posterior Chamber Collamer Lens with CentraFLOW and Its Correlation with ICL Vault and Intraocular Pressure. J Ophthalmol. 2016;2016:1383289.
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22. Fernández-Vigo JI, Macarro A, Fernández-Vigo C, et al. Effects of Implantable Collamer Lens V4c placement on iridocorneal angle measurements by Fourier domain optical coherence tomography. American Journal of Ophthalmology. 2016;162:43-52.e1. 23. Fernández-Vigo JI, De-Pablo-Gómez-De-Liaño L, Fernández-Vigo C, et al. Quantification of trabecular-iris contact and its prevalence by optical coherence tomography in a healthy Caucasian population. Eur J Ophthalmol. 2016;16:0. 24. Guber I, Mouvet V, Bergin C, et al. Clinical Outcomes and Cataract Formation Rates in Eyes 10 Years After Posterior Phakic Lens Implantation for Myopia. JAMA Ophthalmol. 2016. doi: 10.1001/jamaophthalmol.2016.0078.
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ACCEPTED MANUSCRIPT 25. Garcia-Feijóo J, Jimenez Alfaro I, Cuiña-Sardiña R, et al. Ultrasound biomicroscopy examination of posterior chamber phakic intraocular lens position. Ophthalmology 2003;110(1):163-72. 26. Fernández-Vigo JI, García-Feijóo J, Martínez-de-la-Casa JM, et al. Fourier domain optical coherence tomography to assess the iridocorneal angle and correlation study in a large Caucasian population. BMC Ophthalmol. 2016;18;16:42.
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27. Kojima T, Yokoyama S, Ito M, et al. Optimization of an implantable collamer lens sizing method using high-frequency ultrasound biomicroscopy. Am J Ophthalmol 2012;153(4):632-7.
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28. Alfonso JF, Fernández-Vega L, Lisa C, et al. Long-term evaluation of the central vault after phakic Collamer lens (ICL) implantation using OCT. Graefes Arch Clin Exp Ophthalmol 2012;250(12):1807-12.
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29. Foo LL, Nongpiur ME, Allen JC, et al. Determinants of angle width in Chinese Singaporeans. Ophthalmology. 2012;119(2):278-82.
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30. Wang YE, Li Y, Wang D, He M, Lin S. Comparison of factors associated with occludable angle between american Caucasians and ethnic Chinese. Invest Ophthalmol Vis Sci. 2013;54(12):7717-23.
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ACCEPTED MANUSCRIPT Figure captions: Figure 1. Implantable collamer lens position in the ciliary sulcus of the eye.
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Figure 2. Trabecular-iris angle measurements made by Fourier-domain optical coherence tomography before and after Visian implantable collamer lens V4c implantation. Upper row, baseline (left), and one month (middle left), three months (middle right) and two years (right) after surgery. Note that the narrowing produced after surgery (middle left) remained stable after two years (right). Lower row shows the angle measured as angle opening distance in another patient at the same time points (TIA= trabecular-iris angle measured by tracing a 500 µm line from the angle recess toward the Schwalbe's line and another line on the surface of the iris to the point crossing the first line. AOD= angle opening distance 500 µm from the scleral spur).
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Figure 3. Two examples of trabecular-iris contact (TIC) observed by Fourierdomain optical coherence tomography following Visian implantable collamer lens V4c implant. The first example (upper row: left=baseline, middle left= one month, middle= three months, middle right=one year, and right= two years after surgery) shows TIC (measured as trabecular-iris contact length, TICL) detected in a patient three months after surgery (middle). TIC diminished at one year and remained stable at two years of follow up. In the second example (lower row: left=baseline, middle left= one month, middle= three months, middle right=one year, and right= two years after surgery) TIC appeared at one month postimplant (middle left), and contact was most pronounced at 3 months (middle), diminishing at one year (middle right) and remaining stable at two years (right). It is possible to visualize the corneal incision made for surgical access.
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Figure 4. Anterior chamber angle assessed by Fourier-domain optical coherence tomography two years after Visian implantable collamer lens V4c implant. Angle closure associated with trabecular-iris contact was observed in the nasal quadrant (left) over the follow up period. However, the inferior (middle) and the temporal quadrants (right) remained open (TICL= trabecular-iris contact length; TIA= trabecular-iris angle).
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ACCEPTED MANUSCRIPT Preop.
1 month postop.
3 months postop.
1 year postop.
2 years postop.
Spherical error (D)
-8.48 ±4.03
0.10 ± 0.27
0.12 ±0.32
0.05 ±0.19
-0.02 ±0.44
(-21.0, -2.25)
(-0.50, 1)
(0, 1.5)
(0, 1)
(-0.5, 1)
-1.56 ±1.13
-0.30 ±0.58
-0.26 ±0.57
-0.10 ±0.39 (-1.75, 0)
-0.11 ± 0.37 (-1.5, 0)
(-5, 0)
(-2.25, 0)
(-1.75, 0)
1.45 ±0.27
0.05 ±0.09
0.05 ±0.11
0.02 ±0.11 (-0.1, 0.3)
0.02 ±0.10 (-0.1, 0.2)
(1, 1.7)
(-0.1, 0.4)
(-0.1, 0.3)
0.06 ±0.13
0.03 ±0.11
0.01 ±0.10
0.01 ± 0.09 (-0.2, 0.2)
0.01 ± 0.09 (-0.2, 0.2)
(-0.1, 0.4)
(-0.1, 0.3)
(-0.2, 0.2)
2637.9 ±255.6 (2097, 3268)
2609.5 ±241.1 (2063, 3084)
2596.9 ±217.1 (2083, 3026)
2568.3 ±227.9 (2056, 3045)
2480.8 ± 214.3 (2037, 2881)
16.6 ±3.0 (11, 21)
18.4 ±6.8 (9, 45)
Not applicable
589.7 ±279.8 (108, 1240)
BCVA (logMAR) ECC 2 (cells/mm ) IOP (mmHg) Lens vault (µm)
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UCVA (logMAR)
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Cylindrical error (D)
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Variable
15.5 ±2.7 (10, 21)
16.2 ±3.5 (8, 22)
15.5 ±2.5 (11, 21 )
557.5 ±276.7 (80, 1260)
505.6 ± 295.2 (51, 1270)
458.3 ± 258.4 (60, 1220)
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Table 1. Ocular variables recorded in the study population (54 eyes of 27 subjects) before, and 1 month, 3 months, 1 year and 2 years after ICL V4c implantation.
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D= diopters; UCVA= uncorrected visual acuity; BCVA= best-corrected visual acuity; logMAR= logarithm of the minimal angle of resolution; SD= standard deviation; ECC= endothelial cell count; IOP= intraocular pressure; µm= microns.
ACCEPTED MANUSCRIPT Table 2. Anterior chamber angle measurements made in the study population (54 eyes of 27 subjects) before, and 1 month, 3 months, 1 year and 2 years after ICL V4c implantation. Mean ± standard deviation, and range in parenthesis.
AOD500 nasal (µm)
1 year
2 years
P value
49.5 ±8.7
29.9 ±10.4
29.2 ±11.2
26.5 ± 8.8
27.3 ± 8.8
0.133
(27.4 – 67.7)
(10.2 – 55.9)
(0 – 57.9)
48.3 ±9.6
28.4 ±10.8
26.3 ±10.6
(23.3 – 66.3)
(5.4 – 53.4)
(5.7 – 46.5)
49.1 ±8.6
28.8 ±9.7
29.0 ±9.9
(31 – 63.8)
(13.4 – 49.5)
(12.7 – 52.3)
(11 – 40.3)
(12.2 – 39.9)
813.4 ± 237.6
384.2 ± 156.8
378.2 ± 169.9
376.3 ± 121.7
390.1 ± 166.5
(0 – 749)
(115 – 680)
(34 – 731 )
354.7 ± 173.4
335.4 ±163.2
354.1 ±151.9
(38 – 757)
(70 – 702)
328.6 ± 148.5
(120 – 697)
(397 – 1410)
AOD500 inferior (µm)
845.1 ± 305.4 (297 – 1260) 836.2 ± 236.4
400.6 ± 136.2
24.9 ± 9
26.8 ± 8.1
(4.2 – 41.8)
(5.3 – 40.8)
27.6 ± 6.5
28.9 ± 7
402 ± 125.3
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1.000
1.000
258 ± 203
307 ± 288
291 ± 195
225 ± 142
(81 – 588)
(85 – 843)
(98 – 529)
(77 – 495)
N= 8
N= 8
N= 8
1.000
(217 – 721)
TIA= trabecular-iris angle; AOD500= angle opening distance 500 microns from the scleral spur; TICL= Trabecular-iris contact length.
b
1.000
(45 – 748)
(154 – 658)
N= 5
0.376
(41 – 680)
(117 – 906)
(188 – 761)
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a
Not applicable
(0 – 41.7)
387.3 ± 124.5
(453 – 1300) TICL (µm)
(0 – 41.4)
404.9 ± 154.2
TE D
AOD500 temporal (µm)
RI PT
TIA inferior (degrees)
3 month postop
SC
TIA temporal (degrees)
1 month postop
M AN U
TIA nasal (degrees)
Preop
P value (level of significance): difference between 1 month and 2 years, adjusted with Generalized Estimating Equations.
0.159
ACCEPTED MANUSCRIPT Table 3: Multivariate analysis of variables affecting anterior chamber temporal angle 2 years after implantable collamer lens V4c implant in 54 eyes of 27 subjects B
95% CI
P value
Constant
23.33
-21.45, 68.11
.273
TIA preop. (degrees)
0.57
0.36, 0.78
.000
Age (years)
-0.874
-1.21, -0.53
Sex (female)
-11.07
-16.55, -5.59
Spherical error (diopters)
-0.40
-0.74, -0.06
Iris thickness (IT500) (µm)
-0.038
-0.06, -0.01
White-to-white distance (mm)
8.52
IOL size (mm)
-5.46
SC
M AN U
a
RI PT
Variable
.000
.001
.026
.007
5.23, 11.81
.000
-10.92, -0.01
.045
Multivariate linear stepwise regression model used to determine factors affecting postoperative TIA.
b
AC C
EP
TE D
TIA= trabecular-iris angle; ACD= anterior chamber depth; iris thickness (IT500) at the perpendicular point 500 µm to the scleral spur; IOL= Intraocular lens; 95% CI= confidence interval at 95%; B= unstandardized coefficient.
ACCEPTED MANUSCRIPT IOP
TIA preop.
ACD preop.
WTW preop.
TIA nasal 1 month postop.
-0.483 (p= .001)
0.060 (p= .500)
0.525 (p= .000)
0.229 (p= .240)
-0.041 (p= .750)
TIA temporal 1 month postop.
-0.535 (p= .001)
0.096 (p= .359)
0.437 (p= .001)
0.053 (p= .742)
-0.036 (p= .734)
TIA inferior 1 month postop.
-0.638 (p= .001)
0.002 (p= .399)
0.413 (p= .000)
0.047 (p= .719)
-0.130 (p= .238)
AOD500 nasal 1 month postop.
-0.493(p= .001)
0.126 (p= .699)
0.489 (p= .000)
0.169 (p= .346)
-0.122 (p= .426)
AOD500 temporal 1 month postop.
-0.554 (p= .001)
0.142 (p= .189)
0.437 (p= .000)
0.101 (p= .595)
-0.037 (p= .809)
AOD500 inferior 1 month postop.
-0.612 (p= .001)
-0.092 (p= .511)
0.422 (p= .000)
0.102 (p= .408)
-0.070 (p= .566)
TIA nasal 2 years postop.
-0.448 (p= .001)
-0.342 (p= .050)
0.549 (p= .000)
0.218 (p= .119)
-0.170 (p= .456)
TIA temporal 2 years postop.
-0.609 (p= .000)
-0.258 (p= .137)
0.499 (p= .000)
0.230 (p= .189)
-0.202 (p= .362)
TIA inferior 2 years postop.
-0.686 (p= .001)
-0.336 (p= .131)
0.528 (p= .000)
0.082 (p= .688)
-0.004 (p= .984)
AOD500 nasal 2 years postop.
-0.509 (p= .001)
-0.431 (p= .006)
0.526 (p= .000)
0.202 (p= .277)
-0.125 (p= .567)
AOD500 temporal 2 years postop.
-0.531 (p= .003)
-0.328 (p= .043)
0.462 (p= .002)
0.283 (p= .164)
-0.242 (p= .315)
AOD500 inferior 2 years postop.
-0.6037 (p= .001)
-0.349 (p= .110)
0.469 (p= .000)
0.084 (p= .609)
-0.014 (p= .932)
EP
TE D
M AN U
SC
RI PT
Lens vault
a
AC C
Table 4. Correlations between angle measurements and the ocular factors examined in the study population. Pearson correlation (R) was used for trabecular-iris angle (TIA), correcting for patient cluster. For the non-normally distributed AOD500 data, Spearman’s Rho was used. b
Lens vault= distance from posterior ICL surface to anterior crystalline lens surface; IOP= intraocular pressure; ACD= anterior chamber depth; WTW= white to white distance; TIA= trabecular-iris angle; AOD500= angle opening distance 500 microns from the scleral spur. c
Lens vault and IOP measurements were compared at one-month and threemonths of follow up as the time when the angle measurements were made. 1
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT