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ORIGINAL ARTICLE Visual Outcomes and Safety of a Refractive Corneal Inlay for Presbyopia Using Femtosecond Laser Aliki N. Limnopoulou, MD, MSc; Dimitrios I. Bouzoukis, MD, FEBO; George D. Kymionis, MD, PhD; Sophia I. Panagopoulou, PhD; Sotiris Plainis, PhD; Aristophanes I. Pallikaris, MSc; Vladimir Feingold; Ioannis G. Pallikaris, MD, PhD ABSTRACT PURPOSE: To evaluate the outcomes and safety of a refractive inlay (Flexivue Micro-Lens, Presbia Coöperatief U.A.) for the corneal compensation of presbyopia. METHODS: This prospective, interventional clinical study comprised 47 emmetropic presbyopes with a mean age of 52⫾4 years (range: 45 to 60 years). The inlay was inserted, centered on the line of sight, inside a corneal pocket created in the patient’s nondominant eye, using a femtosecond laser. Follow-up was 12 months. Visual acuity, corneal topography, wavefront aberrometry, contrast sensitivity, structural corneal alterations, and questionnaires were evaluated. RESULTS: Twelve months after surgery, uncorrected near visual acuity was 20/32 or better in 75% of operated eyes, whereas mean uncorrected distance visual acuity (UDVA) of operated eyes was statistically significantly decreased from 0.06⫾0.09 logMAR (20/20) (range: ⫺0.08 to 0.26) preoperatively to 0.38⫾0.15 logMAR (20/50) (range: 0.12 to 0.8) (P⬍.001), and mean binocular UDVA was not significantly altered (P=.516). Seventeen patients lost one line of corrected distance visual acuity in the operated eye. No patient lost 2 lines in CDVA in the operated eye. Overall, higher order aberrations increased and contrast sensitivity decreased in the operated eye. No tissue alterations were found using corneal confocal microscopy. No intra- or postoperative complications occurred. CONCLUSIONS: Twelve months after implantation, the Flexivue Micro-Lens intracorneal refractive inlay seems to be an effective method for the corneal compensation of presbyopia in emmetropic presbyopes aged between 45 and 60 years old. [J Refract Surg. 2013;29(1):12-18.] D uring the past decade in the field of refractive surgery there has been an increasing interest in the use of corneal inlays for the treatment of presbyopia. These may be implanted using flaps created by microkeratomes1,2 or femtosecond lasers,3,4 or pockets created by microkeratomes5,6 or femtosecond lasers.7 It is believed that inlays have the advantage of being minimally invasive and easily reversible. In this study, we prospectively evaluated the efficacy and safety of a refractive intrastromal inlay (Flexivue Micro-Lens; Presbia Coöperatief U.A., Amsterdam, Netherlands) for the corneal compensation of presbyopia, using a femtosecond laser for creation of the pocket. PATIENTS AND METHODS This prospective, noncomparative, nonrandomized, interventional clinical study was performed at the Institute of Vision and Optics, University Hospital of Crete, Greece. Postoperative follow-up was scheduled at 1, 3, 6, 9, and 12 months. The study followed the tenets of the Declaration of Helsinki and permission was obtained from the ethics committee of the University Hospital of Crete. After receiving a detailed explanation of the study procedures, patient responsibilities, and possible complications, all patients signed informed consent. REFRACTIVE CORNEAL INLAY The Flexivue Micro-Lens is a transparent, hydrophilic concave-convex disc, manufactured from an optically clear copo- From the Department of Ophthalmology, Vardinoyannion Eye Institute of Crete (Limnopoulou, Bouzoukis, Kymionis, Panagopoulou, Plainis, A.I. Pallikaris, I.G. Pallikaris), Crete, Greece; and Presbia Coöperatief U.A., Amsterdam, Netherlands (Feingold). Supported by Presbia Coöperatief U.A. Medical Board. doi:10.3928/1081597X-20121210-01 Drs. Pallikaris and Feingold are employed by and have received funding from Presbia Coöperatief U.A. The remaining authors have no financial or proprietary interest in the materials presented herein. Correspondence: Aliki N. Limnopoulou, MD, MSc, Institute of Vision and Optics (IVO), University of Crete, Medical School, 71003 Heraklion, Crete, Greece. Tel: 30 2810 371800; Fax: 30 2810 39465; E-mail: [email protected] Received: May 7, 2012; Accepted: October 12, 2012 12 Copyright © SLACK Incorporated Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al Figure 1. Flexivue Micro-Lens intracorneal inlay. TABLE 1 Femtosecond-assisted Pocket Laser Parameters Femtosecond laser iFS 150 Treatment type inlay Channel width (mm) 4.20 Channel offset (mm) 0.00 Channel depth (µm) 280 Channel spot separation 2 Channel line separation 2 Channel energy (µJ) 0.75 Side cut radius (mm) 4.50 Side cut angle (°) 30 Side cut spot separation (µm)/ Side cut layer separation (µm) 3/3 Side cut energy (µJ) 1.20 (iFS 150; Abbott Medical Optics, Santa Ana, California) lymer of hydroxyethylmethacrylate and methylmethacrylate containing an ultraviolet blocker. The inlay has a 3-mm diameter and a thickness of approximately 15 to 20 μm, depending on the additional power, which acts by changing the refractive index of the cornea. The lens material refractive index is 1.4583 and has a light transmission ⬎95% at wavelengths above 410 nm. The central 1.8-mm diameter of the disc is plano in power and the peripheral zone has the appropriate addition power. The available inlay refractive power ranges from ⫹1.25 diopters (D) to ⫹3.50 D in 0.25-D increments. At the center of the disc, a 0.15-mm diameter hole facilitates the transfer of oxygen and nutrients into the cornea through the lens. Figure 1 depicts the design of the Flexivue Micro-Lens inlay and Figure 2 shows a representative patient after implantation. During far vision, rays passing through the central zone of the implant and the free peripheral corneal tissue without the lens added refractive effect will be Journal of Refractive Surgery • Vol. 29, No. 1, 2013 Figure 2. Patient 1 year after intracorneal inlay implantation showing clarity of the cornea and absence of interference with slit-lamp examination of the anterior segments of the globe. sharply focused on the retina, whereas rays that pass through the refractive peripheral zone of the inlay will be focused in front of the retina. During near vision, rays passing through the central zone of the implant will be out of focus behind the retina and rays passing through the peripheral clear cornea will be blocked by the pupil. The rays passing through the peripheral refractive zone of the inlay will be focused on the retina. SURGICAL TECHNIQUE The surgical procedure was performed under topical anesthesia using proxymetacaine hydrochloride 0.5% eye drops (Alcon Laboratories Inc, Ft Worth, Texas). The intracorneal pocket was created using a femtosecond laser (IntraLase 150; Abbott Medical Optics, Santa Ana, California). Using appropriate software, a full lamellar cut was created at a depth of 280-μm with a diameter of 9.00 mm and a line/spot separation of 2/2 μm. Table 1 shows the femtosecond laser parameters of the procedure. The tunnel was created from the temporal incision cut to the center of the cornea corresponding to the visual axis. A special injector (Presbia Coöperatief U.A.) was used to implant the inlay inside the tunnel at the line of sight. To determine the line of sight, the microscope and centration device of the excimer laser (Allegretto Wave 400; WaveLight Technologie AG, Erlangen, Germany)8 were used. Postoperatively, patients were treated with fluorometholone 0.1% (Falcon Pharmaceuticals, Ft Worth, Texas) four times daily tapering over 1 week, along with antibiotic drops (0.1% dexamethazone and 0.5% chloramphenicol) and artificial tears. PATIENT CRITERIA Inclusion criteria were patients aged between 45 and 60 years with uncorrected near visual acuity (UNVA) worse than 0.40 logMAR (20/50), uncorrected distance 13 Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al TABLE 2 Demographic Data Demographic Value (Mean⫾SD [Range]) No. of patients 47 Follow-up (mo) 12.6 (9 to 15) Males/females 20/27 Right/left eyes 19/28 Age (y) Implanted inlay (D) 51.55⫾4.11 (45 to 60) 2.48⫾0.22 (⫹1.75 to ⫹3.25) UDVA (Snellen equivalent) 20/25 or better (20/25 to 20/16) CDVA (Snellen equivalent) 20/20 or better (20/20 to 20/12) Spherical equivalent refraction (distance) (D) 0.66⫾0.35 (0.00 to ⫹1.25) UNVA (Snellen equivalent) 20/50 or worse (20/50 to 20/80) CNVA (Snellen equivalent) 20/25 or better (20/25 to 20/20) Spherical equivalent refraction (near) (D) 2.20⫾0.23 (1.75 to 2.90) Corneal thickness (µm) 546.5⫾22.4 (508 to 599) SD = standard deviation, UDVA = uncorrected distance visual acuity, CDVA = corrected distance visual acuity, UNVA = uncorrected near visual acuity, CNVA = corrected near visual acuity visual acuity (UDVA) of 0.20 logMAR (20/32) or better in either eye, and corrected near visual acuity (CNVA) and corrected distance visual acuity (CDVA) of 0.10 logMAR (20/25) or better, respectively. Cycloplegic sphere ranged between ⫺0.75 and ⫹0.75 diopters (D), astigmatism ⬍1.00 D, and stable refraction (within ⫾0.50 D) for a 1-year period prior to implantation. All patients wore reading glasses at least 1 year prior to the preoperative evaluation. Central corneal pachymetry ⬎500 μm and endothelial cell density ⬎2000 cells/ mm2 on specular microscopy was necessary in the eye to be operated. Exclusion criteria were irregular astigmatism, pupil diameter ⬍3 mm in photopic conditions, lens opacities that may affect vision, history of congenital or acquired anterior or posterior segment pathology or history of ocular surgery, and acute or chronic systemic disease or any kind of immunosuppressive disorder. CLINICAL EXAMINATION A complete ophthalmic examination was performed preoperatively and during each postoperative followup evaluation in all patients. Visual Acuity Testing. Distance visual acuity was tested using Early Diabetic Retinopathy Study (ETDRS) logMAR charts (Precision Vision, La Salle, Illinois) at 4 m distance. Near visual acuity was tested at 33 cm under a light source of 100 cd/m2 using the modified 14 ETDRS chart for European wide use (Precision Vision). All tests were performed monocularly and binocularly. The dominant eye was determined using a card with a central 1-inch hole test and confirmed with four dots test, and a monovision trial was performed for at least 30 minutes, adding half of the add power for near in the nondominant eye. Additionally, to evaluate the effect of the inlay on distance vision, postoperative UDVA was compared with preoperative distance visual acuity in which a lens of equal refractive power with the lens that was intended to be implanted was used. The wavefront aberration function of the eye was measured at scotopic condition with natural (undilated) pupils using the WASCA COAS Wavefront Analyzer (Carl Zeiss Meditec, Jena, Germany), which is based on the Shack-Hartmann principle. Corneal topography and corneal aberrations were measured using the Topolyzer topographic system (Wavelight Topolyzer, WaveLight Technologie AG). Aberration coefficients, aligned to the pupil center, were analyzed for 3- and 4-mm pupil diameters for the total eye, and for 3- and 6-mm pupil diameters for the cornea. Contrast sensitivity was measured using the Functional Acuity Contrast Test (Stereo Optical Co Inc, Chicago, Illinois) in photopic and mesopic conditions (with and without glare), binocularly, and monocularly. All measurements were performed in a room without windows, with the lights on for measurement under photopic conditions and off for measurement under mesopic conditions and the door sealed. Photopic and mesopic conditions were standardized by the machine at 200 lux for the photopic conditions and at 1 lux for the mesopic conditions. Corneal structure was evaluated using confocal microscopy with a modified confocal scanning laser ophthalmoscope (HRT II; Heidelberg Engineering, Heidelberg, Germany). Images of the various layers of the cornea were acquired at the optical center of the cornea and at the sites adjacent to or at the corneal inlay. Quantitative analysis of endothelial cell density was performed by counting cells from the confocal microscope. The automated counter was at a distant location, which was too far for every patient to attend to. Other evaluation tests included tonometry (Goldmann applanation tonometry) and central and peripheral ultrasound corneal pachymetry (50 MHz [Corneo-Gage Plus; Sonogage Inc, Cleveland, Ohio]). During the preoperative evaluation, a detailed discussion with each patient revealed his/her ideal distance of work, the amount of dependence on spectacles for near vision, as well as his/her overall satisfaction regarding vision throughout the day. Postoperatively, patients were asked to complete a satisfaction questionCopyright © SLACK Incorporated Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al Figure 3. Accuracy of the intended additional power in diopters needed for corrected near visual acuity after inlay implantation. Figure 4. Respective percentages of mean uncorrected near visual acuity (logMAR) of operated eyes in patients during follow-up. naire for the evaluation of UNVA, UDVA, frequency of eventual use of reading glasses, and for the presence or absence of halos or glare. STATISTICAL ANALYSIS Statistical analysis was performed using SPSS 16.0 statistical package (SPSS Inc, Chicago, Illinois). All values were monitored for normality with the Shapiro– Wilks test and because their frequency distribution was normal, variables were expressed as mean⫾standard deviation. A P value ⬍.05 was considered statistically significant. Paired Student t tests were performed to compare mean values of the variables described. Wavefront aberrations and contrast sensitivity were evaluated with the Wilcoxon signed ranks test, because their frequency distributions were not normal. RESULTS Patient demographics are depicted in Table 2. All patients attended scheduled 12-month postoperative follow-up examinations. VISUAL OUTCOMES Accuracy. Figure 3 shows a histogram of the accuracy of attempted correction for near vision based on postoperative add power. One year after treatment, additional power needed for CNVA was within ⫾0.50 D in 99% of operated eyes. Journal of Refractive Surgery • Vol. 29, No. 1, 2013 Efficacy and Stability. One year postoperatively, mean UNVA significantly improved from 0.68⫾0.03 logMAR (20/100) (range: 0.40 to 1.00 [20/50 to 20/200]) to 0.14⫾0.09 logMAR (20/25) (range: ⫺0.02 to 0.36 [20/12 to 20/50]) (P⬍.001) in operated eyes, and from 0.53⫾0.13 logMAR (20/60) (range: 0.34 to 0.73 [20/40 to 20/100]) preoperatively to 0.13⫾0.13 logMAR (20/25) (range: 0.00 to 0.38 [20/20 to 20/50]) binocularly (P⬍.001). Figure 4 shows a histogram with the cumulative results for the UNVA of the operated eyes achieved at each follow-up. Uncorrected near visual acuity of the operated eyes was 20/32 or better in 75% of patients 12 months after inlay implantation. Mean UDVA in operated eyes significantly decreased from 0.06⫾0.09 logMAR (20/25) (range: ⫺0.08 to 0.26 [20/16 to 20/40]) preoperatively to 0.38⫾0.15 logMAR (20/50) (range: 0.12 to 0.8 [20/25 to 20/125]) (P⬍.001), whereas binocularly it did not change significantly (P=.516). Mean UDVA of the operated eyes, achieved 1 year after implantation, was compared to the mean preoperative CDVA of the same eyes, which were corrected with a spherical lens power equal to the intended power of the inlay. It was demonstrated that distance vision was less influenced, as mean UDVA of the operated eyes was 0.38⫾0.15 logMAR (20/50) (range: 0.12 to 0.8), as opposed to 0.78⫾0.09 logMAR (20/125), which would be expected (P⬍.001). 15 Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al At last follow-up, mean spherical equivalent refraction of the operated eyes changed significantly from 0.66⫾0.35 D (range: 0 to ⫺1.25 D) preoperatively to ⫺1.95⫾1.32 D (range: ⫺3.88⫾0.25 D) (P⬍.001). Mean spherical equivalent refraction of the operated eyes was not statistically significant during the postoperative period. Twelve months after implantation, mean cylinder of the operated eyes was 0.72 D and was not significantly different from preoperatively (⫺0.25 D) (P=.07). SAFETY AND COMPLICATIONS At last follow-up, 37% (17) of patients had lost 1 line of CDVA (0.1 logMAR [20/25]) in the operated eye with a statistically significant decrease from 0.00⫾0.05 logMAR (20/20) (range: ⫺0.08 to 0.18 [20/16 to 20/30]) preoperatively to 0.10⫾0.05 logMAR (20/25) (range: ⫺0.06 to 0.20 [20/16 to 20/32]), whereas no significant decrease (P=.13) in CDVA was found binocularly. No patient lost ⬎2 lines in CDVA in the operated eye. Corrected near visual acuity of operated eyes, as well as binocularly, remained unchanged during follow-up (P=.8). Mean central corneal thickness of the operated eyes did not change significantly after implantation (546.5⫾22.4 μm preoperatively to 548.87⫾25.58 μm, P=.132). Change in mean intraocular pressure of the operated eyes was not statistically significant (P=.452). No intra- or postoperative complications were demonstrated and no removal or replacement of any refractive intracorneal inlay was performed. WAVEFRONT ANALYSIS, CONTRAST SENSITIVITY FUNCTION, AND TOPOGRAPHY The RMS of higher order ocular aberrations changed from 0.33⫾0.14 to 0.79⫾0.17 μm (P⬍.001) at 3-mm pupil diameter and from 0.52⫾0.20 to 1.15⫾0.29 μm (P⬍.001) at 4-mm pupil diameter 12 months after implantation. The RMS of spherical ocular aberration changed from 0.02⫾0.02 to 0.08⫾0.04 μm (P=.001) at 3-mm pupil diameter and from 0.05⫾0.04 to 0.19⫾0.06 μm (P⬍.001) at 4-mm pupil diameter. The Appendix (available as supplemental material in the PDF version of this article) shows the changes in all higher order aberration terms in RMS for the total eye at 3 and 4 mm preoperatively and 12 months postoperatively. The RMS of higher order corneal aberrations changed from 0.14⫾0.05 to 0.22⫾0.08 μm (P=.003) at 3-mm pupil diameter and from 0.34⫾0.10 to 0.55⫾0.20 μm (P⬍.001) at 6-mm pupil diameter. The RMS of spherical corneal aberration changed from 16 0.03⫾0.03 to 0.09⫾0.07 μm (P=.008) at 3-mm pupil diameter and from 0.10⫾0.05 to 0.13⫾0.09 μm (P=1.00) at 6-mm pupil diameter. The Appendix shows the changes in all higher order aberration terms in RMS for the cornea at 3 and 6 mm preoperatively and 12 months postoperatively. Corneal topographic astigmatism was ⫺0.72⫾0.33 D (range: ⫺0.12 to ⫺1.40 D) and changed to ⫺1.23⫾0.31 D (range: –0.70 to ⫺1.81 D) (P=.005). Mean surgically induced astigmatism was ⫺0.44⫾0.19 D (range: ⫺0.18 to ⫺0.83 D) at mean axis of 169°⫾22°. Change in contrast sensitivity of the operated eye 1 year postoperatively in mesopic conditions was statistically significant at 1.5 cycles per degree (cpd) (P=.009), 6 cpd (P=.012), and 12 cpd (P=.002), whereas in photopic conditions it was statistically significant at 6 cpd (P=.007), 12 cpd (P⬍.001), and 18 cpd (P⬍.001). Change in binocular contrast sensitivity in mesopic conditions was significant only at 1.5 cpd (P=.049) and in photopic conditions was not significantly different at any frequency from the preoperative values. ENDOTHELIAL CELL DENSITY AND CONFOCAL MICROSCOPY Normal epithelial cells, subepithelial nerve plexus, keratocyte scattering, and endothelial morphology were observed in all patients at depths below and above the inlay after 1 year. Endothelial cell counts in the operated eyes were not significantly changed (P=.776) 12 months after surgery, from preoperative measurement of 2536⫾225 cells/mm2 to 2442⫾269.84 postoperatively (range: 2104 to 2899 cells/mm2). PATIENT SATISFACTION QUESTIONNAIRE During the preoperative evaluation, patients answered questions about their profession, everyday needs, frequency of using a computer, and preferable distance of working. These questions assisted the surgeon in deciding on the ideal inlay power for each patient. A general complaint about their inability to function without spectacles for near vision, annoyance for constantly having to put them on and off, and satisfactory UDVA were noted. Twelve months after implantation, 81.25% of patients perceived their UNVA in the operated eye as excellent, whereas 93.75% were independent of their near spectacles, with 6.25% of patients using spectacles for near tasks for less than half of everyday use. No patient used spectacles for distance vision. During the last follow-up, 81.25% of patients perceived their binocular UDVA as excellent compared to 53.33% at 1 month postoperatively, and 18.75% described it as good. As for UDVA of the operated eye, 1 Copyright © SLACK Incorporated Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al year after surgery, 18.75% of patients perceived it as excellent and 81.25% as good. One year after the procedure, 12.5% of patients still experienced halos and 12.5% experienced glare. DISCUSSION In the present study, the outcomes of the use of a refractive corneal inlay (Flexivue Micro-Lens) in emmetropic presbyopes were evaluated. After implantation of the Flexivue Micro-Lens using a femtosecond laser for creation of the pocket, mean UNVA improved to 0.13 logMAR (20/25). Mean UDVA of the operated eyes decreased to 0.38 logMAR (~20/50), but this change was less than what would be expected if compared to the distance visual acuity tested preoperatively using a lens with a refractive power equal to that of the inlay. Corrected distance visual acuity decreased in 37% of patients, but no inlay removal was required as patients were satisfied with their binocular UNVA and UDVA. The change in CDVA may be attributed to the difficulty in performing manifest refraction over the inlay, because of its two separate focal points. Other types of corneal inlays have been used previously.1-7,9 The ACI-7000 (Acufocus Inc, Irvine, California) is a small quasi-opaque inlay placed in the stromal bed after creation of a conventional flap in the nondominant eye, which increases the depth of focus by incorporating a small central clear aperture 1.6 mm in diameter. Yilmaz et al1 reported that after implantation of the ACI-7000 using a microkeratome, 85.3% of patients recorded UNVA binocularly as J1 or better and Seyeddain et al3 reported that 2 years after implantation of the ACI-7000 using a femtosecond laser for the creation of the pocket, 96.9% of patients achieved J3 or better. The PresbyLens (ReVision Optics Inc, Lake Forest, California) is a different corneal inlay, which when placed under a 120-μm flap, induces steepening of the anterior curvature of the central cornea. Slade,8 who presented 6-month results of PresbyLens inlay implantation in natural and postoperative refractive emmetropic presbyopes, reported mean UNVA of 20/25 and no patient lost ⬎2 lines regarding distance vision. The Invue lens (Biovision AG, Brugs, Switzerland) is another corneal inlay implanted inside a corneal pocket of the nondominant eye using a microkeratome. Bouzoukis et al6 reported improved near visual acuity, with 98% of patients achieving UNVA of 20/32. In this study, total eye wavefront aberration analysis showed a statistically significant increase in total higher order aberrations as well as mean spherical aberration at 3- and 4-mm pupil diameter. Additionally, the RMS of the spherical aberration of the cornea was increased at 3-mm pupil diameter. The corneal inlay has a plano 1.8Journal of Refractive Surgery • Vol. 29, No. 1, 2013 mm diameter in the center, whereas the annular peripheral zone (from 1.8 to 3.0 mm) has the add power creating a myopic effect. It is expected that both the corneal and “total eye” higher order aberrations are influenced by the implanted lens. A potential reason for the increase in higher order aberrations is the decentration of the inlay (in combination with its refractive periphery). In practice, the surgeon attempts to align the inlay with the coaxially sighted corneal reflex, but it remains unclear whether another position would improve optical quality with respect to centration of the corneal reflex. In any case, an increase in the higher order aberrations in the nondominant eye possibly further extends its depth of focus. A similar increase was reported by Alió et al10 for correcting hyperopia with intracorneal hydrogel inlays after flap creation. Increased aberrations may influence distance visual performance, but could also positively contribute to near vision by increasing ocular depth of focus. Charman11 noted the main requirement in presbyopia is an extended depth of focus to assure adequate near and distance vision with good retinal contrast, rather than achieving the highest level of acuity and modulation transfer function at a single distance. As he suggested, an increase in the depth of focus could be accomplished by aiming at residual higher order aberrations. Similar increases were also reported for other inlays by Mulet et al2 using a corneal flap and Bouzoukis et al6 using a corneal pocket created by a microkeratome. The observed significant decrease in contrast sensitivity at high spatial frequencies (operated eyes) may be attributed to induced aberrations.12,13 Mean central corneal thickness was not statistically significantly different after implantation. This fact could be related either to the thinness of the inlay (15 to 20 μm), which is even thinner than the standard deviation of the measurements, or to the sound transmission change resulting in artifactual thickness evaluation. However, as the central corneal thickness and endothelial cell density were stable, along with the confocal findings of healthy keratocytes, the procedure appears safe in early follow-up. No evidence of biocompatibility problems was noted with this inlay. These results suggest that intrastromal inlay implantation may not lead to corneal thinning or corneal melting within the first 12 months. Patient satisfaction was high, as 81.25% of patients perceived their UNVA as excellent 1 year after the procedure. Twelve months after implantation, 93.75% of patients were independent of spectacles for all everyday near activity, compared to the fact that the majority of patients were depending on spectacles for all near activity prior to surgery. During the same time period, 81.25% of patients perceived their UDVA as excellent. 17 Refractive Corneal Inlay With a Femtosecond Laser-created Pocket/Limnopoulou et al The majority of patients reported the presence of glare and halos from the first postoperative month, which tended to become less intense during follow-up and did not interfere with activities such as driving at night. Homogeneity of the ocular structures affects retinal image quality. Light scattered from the edge of the inlay spreads at larger angles over the retina and possibly contributes to the observed increase in glare and halos. This would probably be more evident in cases where the inlay is slightly tilted. It is not expected to be remarkable when using a femtosecond laser to create the pocket, as was the case in our study. The depth of the implantation was selected to be 280 μm, as the posterior stroma of the cornea has reduced concentrations of keratocytes, which may improve tolerability of the inlay. Confocal images of the corneal stroma did not reveal signs of instability. Larrea et al14 considered depth of implantation at 3/5 of the corneal stroma, using computational methods, as optimal to facilitate nutrient flow and oxygen transport. Patients with thinner corneas should be evaluated after inlay implantation and a corneal pocket created by a femtosecond laser may be able to expand the inclusion criteria. Femtosecond laser technology has offered a new surgical approach in corneal refractive surgery.15 The creation of femtosecond laser–assisted pockets could improve the surgical procedure and increase the precision of the inlay position. Possible limitations to our study include the length of follow-up and the number of patients included. A larger number of patients with a longer observation period is needed to confirm the stability and long-term safety of the inlay implantation. Stereopsis evaluation is another suggestion for future studies. At 12 months postoperatively, implantation of the Flexivue Micro-Lens in a femtosecond laser–created pocket was a minimally invasive, effective surgical treatment for presbyopes aged between 45 and 60 years. AUTHOR CONTRIBUTIONS Study concept and design (D.I.B., S.P., A.I.P., V.F., I.G.P.); data collection (A.N.L., A.I.P.); analysis and interpretation of data (A.N.L., D.I.B., G.D.K., S.I.P., A.I.P., V.F., I.G.P.); drafting of the manuscript (A.N.L.); critical revision of the manuscript (D.I.B., G.D.K., S.I.P., S.P., A.I.P., V.F., I.G.P.); statistical expertise (A.N.L., S.I.P.); 18 obtained funding (I.G.P.); administrative, technical, or material support (A.I.P.); supervision (D.I.B., V.F., I.G.P.) REFERENCES 1. Yilmaz OF, Bayraktar S, Agca A, Yilmaz B, McDonald MB, van de Pol C Intracorneal inlay for the surgical correction of presbyopia. J Cataract Refract Surg. 2008;34(11):1921-1927. 2. Mulet ME, Alio JL, Knorz MC. 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Copyright © SLACK Incorporated APPENDIX Higher Order Aberrations Preoperatively and 12 Months Postoperatively Root-Mean-Square (µm) Zernike RMS Z-33 Z-13 Z31 Z33 Z-44 Z-24 Z40 Z42 Z44 HOAs Total Eye Pupil Diameter (mm) Preop Postop 3 0.03⫾0.02 0.05⫾0.03 4 0.07⫾0.05 3 0.02⫾0.02 4 3 Corneal Pupil Diameter (mm) Preop Postop P Value .381 3 0.05⫾0.04 0.08⫾0.09 1.000 0.09⫾0.06 .113 6 0.09⫾0.07 0.35⫾0.23 ⬍.001 0.06⫾0.04 .005 3 0.04⫾0.03 0.07⫾0.05 .213 0.05⫾0.03 0.11⫾0.07 .002 6 0.12⫾0.09 0.14⫾0.10 1.000 0.03⫾0.03 0.14⫾0.10 .001 3 0.04⫾0.03 0.05⫾0.04 1.000 4 0.06⫾0.06 0.29⫾0.13 ⬍.001 6 0.12⫾0.10 0.11⫾0.08 1.000 3 0.02⫾0.02 0.05⫾0.04 .001 3 0.06⫾0.04 0.07⫾0.06 1.000 4 0.04⫾0.03 0.12⫾0.09 .001 6 0.16⫾0.12 0.17⫾0.13 1.000 P Value 3 0.01⫾0.01 0.01⫾0.01 .055 3 0.03⫾0.02 0.04⫾0.03 .787 4 0.02⫾0.02 0.04⫾0.02 .003 6 0.05⫾0.04 0.07⫾0.06 1.000 3 0.01⫾0.003 0.03⫾0.02 .001 3 0.02⫾0.01 0.02⫾0.02 1.000 4 0.01⫾0.01 0.03⫾0.02 .007 6 0.03⫾0.03 0.03⫾0.03 1.000 3 0.02⫾0.02 0.08⫾0.04 .001 3 0.03⫾0.03 0.09⫾0.07 .008 4 0.05⫾0.04 0.19⫾0.06 ⬍.001 6 0.10⫾0.05 0.13⫾0.09 1.000 3 0.01⫾0.01 0.04⫾0.04 .004 3 0.03⫾0.05 0.04⫾0.03 1.000 4 0.02⫾0.02 0.03⫾0.03 .356 6 0.05⫾0.04 0.04⫾0.04 1.000 3 0.01⫾0.006 0.02⫾0.01 .068 3 0.04⫾0.03 0.06⫾0.04 .548 4 0.02⫾0.01 0.05⫾0.03 .006 6 0.04⫾0.04 0.17⫾0.11 ⬍.001 3 0.33⫾0.14 0.79⫾0.17 ⬍.001 3 0.14⫾0.05 0.22⫾0.08 .003 4 0.52⫾0.20 1.15⫾0.29 ⬍.001 6 0.34⫾0.10 0.55⫾0.20 ⬍.001 RMS = root-mean-square, HOAs = higher order aberrations