*Article* **Short-Term Efficacy and Safety of Cataract Surgery Combined with Iris-Fixated Phakic Intraocular Lens Explantation: A Multicentre Study**

**Miki Kamikawatoko Omoto 1, Hidemasa Torii 1, Sachiko Masui 1, Masahiko Ayaki 1, Ikuko Toda 2, Hiroyuki Arai 3,4, Tomoaki Nakamura 5, Kazuo Tsubota <sup>1</sup> and Kazuno Negishi 1,\***


**Abstract:** The purpose of this study was to evaluate the short-term efficacy and safety of cataract surgery for patients with iris-fixated phakic intraocular lenses (pIOLs). This study included 96 eyes of 91 patients. The changes in the logMAR uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), subjective spherical equivalent (SE), astigmatism, and endothelial cell density (ECD) were collected retrospectively. The intraoperative and postoperative complications also were investigated to assess the surgical safety. The preoperative UCVA and BCVA improved significantly at month 1 postoperatively, respectively (*p* < 0.001 for both comparisons). The efficacy and safety index at month 1 postoperatively were 1.02 ± 0.56 and 1.31 ± 0.64, respectively. The SE at month 1 postoperatively was significantly (*p* < 0.001) higher compared to preoperatively, whereas the subjective astigmatism did not differ significantly (*p* = 0.078). The ECD significantly decreased at month 1 (*p* < 0.001). The most common postoperative complication was intraocular pressure elevation exceeding 25 mmHg in 10.4% of eyes, which was controlled with medications in all cases until month 1 postoperatively. No intraoperative complications developed. Cataract surgeries for patients with iris-fixated pIOLs were performed safely with good visual outcomes.

**Keywords:** cataract; phakic intraocular lens; multicentre study

#### **1. Introduction**

Uncorrected refractive error is a major cause of visual impairment worldwide [1], and the prevalence of myopia is reported to be growing, especially in Asian countries [2–4]. Implantation of phakic intraocular lens (pIOL) is an option to correct myopia [5,6]. The reversibility when necessary should be an advantage of pIOL implantation compared to laser corneal refractive surgery, such as laser in situ keratomileusis (LASIK). Some studies have reported good long-term outcomes up to 10 years [7–9]. However, some cases need pIOL explantation due to cataract formation or decreased endothelial cell density (ECD) [10–12]. Some studies have reported the safety and efficacy of combined cataract surgery/pIOL explantation; however, small case series [13–17] or case reports of new surgical techniques [18,19], except for the study by Vargas et al., investigated 87 eyes of 55 patients [20]. Furthermore, including the study of Vargas et al., most of these studies focused on posterior-chamber pIOLs. Anterior-chamber pIOLs are associated with a lower rate of cataract formation and pigment dispersion compared to posterior-chamber pIOL [5,21]. However, few studies have investigated pIOL explantation and cataract

**Citation:** Omoto, M.K.; Torii, H.; Masui, S.; Ayaki, M.; Toda, I.; Arai, H.; Nakamura, T.; Tsubota, K.; Negishi, K. Short-Term Efficacy and Safety of Cataract Surgery Combined with Iris-Fixated Phakic Intraocular Lens Explantation:

A Multicentre Study. *J. Clin. Med.* **2021**, *10*, 3672. https://doi.org/ 10.3390/jcm10163672

Academic Editor: Bryan J. Winn

Received: 25 June 2021 Accepted: 17 August 2021 Published: 19 August 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

surgeries for eyes with iris-fixated pIOL. We report the short-term efficacy and safety of cataract surgery with iris-fixated pIOL explantation.

#### **2. Materials and Methods**

#### *2.1. Study Institutions and Institutional Review Board Approval*

This was a multicentre (Keio University Hospital, Minamiaoyama Eye Clinic, Minatomirai Eye Clinic, Queen's Eye Clinic, and Nagoya Eye Clinic), retrospective, observational study. The Research Ethics Committee of the Keio University School of Medicine (approval number: 20190278) approved the study, and the other eye clinics participating in the study were described as collaborators in the ethics committee document and were thus covered under the approval granted by the Keio University School of Medicine. This study was conducted according to the tenets of the Declaration of Helsinki. Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of our research.

#### *2.2. Participants*

One hundred and fifty-nine eyes of 139 patients were enrolled in the study; all had undergone pIOL explantation followed by phacoemulsification and IOL implantation at one of the five hospitals between December 2010 and April 2020. The inclusion criteria were eyes with an iris-fixated pIOL. The exclusion criteria were eyes with a vision-threatening disease except cataract, i.e., keratoconus, retinal detachment, central serous chorioretinopathy, macular edema, glaucoma, and choroidal neovascularization; or eyes that had undergone a previous ophthalmic surgery except pIOL implantation, i.e., LASIK, vitrectomy, and glaucoma surgeries. Therefore, 96 eyes of 91 patients were included in the final analysis.

#### *2.3. Surgical Technique*

Five surgeons performed all of the surgeries. A pIOL was explanted through a temporal or superior sclerocorneal incision (range, 2.4–7.0 mm), the size of which was determined based on the material from which the implanted pIOL was made, i.e., polymethyl methacrylate (PMMA) (Artisan® or Artisan Toric®, Ophtec BV, Groningen, The Netherlands) or silicone (Artiflex®, Ophtec BV). The nylon suture was set when the PMMA lens was explanted, which was left at the site until the end of the study period. Standard phacoemulsification and IOL implantation then were performed through a temporal or superior corneal incision (range, 2.3–2.4 mm). The surgeon chose the type of IOL based on the patient's request. The implanted IOLs are summarized in supplemental Table S1. The IOL power was calculated using Barrett Universal II Formula with the preoperative measurements of axial length, keratometry, and anterior chamber depth. The anterior chamber depth was manually measured and verified for accuracy because the participants had pI-OLs. A topical antibiotic (moxifloxacin hydrochloride) and a corticosteroid (betamethasone sodium phosphate) were administered 3 times daily for one week and a non-steroidal anti-inflammatory agent (diclofenac sodium) for 3 months postoperatively. Drug doses were tapered over the postoperative course.

#### *2.4. Ophthalmologic Examinations*

The uncorrected visual acuity (UCVA) was measured preoperatively and on day 1, week 1, and month 1 postoperatively. The best-corrected VA (BCVA) was measured at the same time points; however, in about half of the cases, this examination was omitted on postoperative day 1. These VAs were calculated in logarithm of the minimum angle of resolution (logMAR) units. The subjective spherical equivalent (SE) and astigmatism were also collected at the same time points. The safety and efficacy index were calculated as the month 1 postoperative BCVA/preoperative BCVA and postoperative UCVA/preoperative BCVA. We calculated these indices because the current surgeries reported in this study were performed on patients without visual impairment in many cases. The decimal VA was used only for these calculations. The ECD was measured preoperatively and month 1 postoperatively using a specular microscope (EM-3000 (TOMEY, Tokyo, Japan) and CellChek SL, Noncon Robo II, or XII (Konan Medical, Hyogo, Japan). The axial length was measured using the IOLMaster 500 or IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany).

#### *2.5. Statistical Analysis*

To reduce the possible bias of including both eyes of a patient, the values between the baseline and each time point were compared using a linear mixed model in which the random effect was the subjects. The linear mixed model adjusts for the hierarchical structure of the data, modeling in a way in which measurements are grouped within subjects [22,23]. This was followed by Dunnett's test for multiple comparisons when comparing the values between the baseline and each time point [24]. Statistical significance was set at 0.05. All analyses were performed using R 4.0.4 (R Foundation for Statistical Computing, Vienna, Austria).

#### **3. Results**

The mean ± standard deviation age of the patients at the time of cataract surgery was 55.0 ± 7.5 years. The duration between the cataract surgery and pIOL implantation was 9.7 ± 3.6 years. Fifty-three eyes received a PMMA phakic IOL and 43 eyes a silicone IOL. The UCVA and BCVA before the cataract surgery were 0.29 ± 0.34 and −0.01 ± 0.17 logMAR, respectively. The ECD was 1,986 ± 732 cells/mm2. The detailed information is summarized in Table 1.


**Table 1.** Demographic data of the study participants.

Values are expressed as the mean ± standard deviation. The date of previous pIOL implantation was unknown in seven eyes and the UCVA before the cataract surgery in one eye. The age at pIOL implantation and duration between the surgeries were calculated without these eyes and the UCVA without the one eye. pIOL, phakic intraocular lens; PMMA, polymethyl methacrylate; UCVA, uncorrected visual acuity; BCVA, best-corrected visual acuity; D, diopters.

> Figure 1A and Table 2 show the changes in the UCVA. The preoperative value significantly improved at day 1, week 1, and month 1 postoperatively (*p* < 0.001 for all comparisons by a linear mixed effect model followed by Dunnett's test). Similarly, the postoperative BCVA improved significantly at week 1 and month 1 (*p* < 0.001 for both comparisons) but not on day 1 (*p* = 1.0, Figure 1B, Table 2). The efficacy and safety indices on postoperative month 1 were 1.02 ± 0.56 and 1.31 ± 0.64, respectively.

> The subjective SE was significantly larger (closer to 0) at all time points (*p* < 0.001 for all comparisons) (Figure 1C, Table 2), whereas the subjective astigmatism was greater on day 1 (*p* = 0.0060) but did not differ significantly at week 1 and month (*p* = 1.0 and *p* = 0.078, respectively) (Figure 1D, Table 2). The preoperative subjective astigmatism was significantly different between the patients with PMMA pIOLs and those with silicone IOLs

(*p* = 0.022, supplemental Figure S1). However, this difference was not found postoperatively. The ECD significantly decreased at month 1 (*p* < 0.001) (Figure 1E, Table 2).

The most common postoperative complication was an intraocular pressure (IOP) elevation exceeding 25 mmHg, which occurred in 10.4% of cases on day 1. With the exception of one case, no elevations were observed at postoperative week 1. Including this case, the IOP of all cases were controlled with medications. Corneal edema was observed in 8.3% of cases on day 1, which were not observed on day 7. No intraoperative complications developed. Other postoperative complications are summarized in Table 3.

**Figure 1.** Box plots of each variable. (**A**) Changes in the uncorrected visual acuity (UCVA), (**B**) best-corrected visual acuity (BCVA), (**C**) spherical equivalent, (**D**) astigmatism, and (**E**) endothelial cell density. \* indicates a significant difference between baseline and each time point. N.S., not significant; D, diopters; logMAR, logarithm of the minimum angle of resolution.


**Table 2.** Changes in each variable.

The values are expressed as the mean ± standard deviation. \* Statistically significant difference between baseline and each time point. UCVA, uncorrected visual acuity; BCVA, best-corrected visual acuity; SE, spherical equivalent; ECD: endothelial cell density; D, diopters.


**Table 3.** Postoperative complications.

IOP, intraocular pressure.

#### **4. Discussion**

In the current study, the efficacy and safety of cataract surgery combined with pIOL explantation were investigated in 96 eyes of 91 patients with an iris-fixated pIOL. This study included the largest number of cataract surgeries with pIOL explantation and was the largest study investigating patients with a iris-fixated pIOL. In a previous study with fewer cases, de Vries et al. [14] reported that the BCVA improved from 0.21 ± 0.21 to 0.17 ± 0.18. In the current study, the BCVA improved significantly from −0.01 ± 0.17 to −0.09 ± 0.10. A simple comparison of the studies was not possible because the baseline values differed in the study of de Vries et al., which included eyes with vision-threatening diseases, such as retinal detachment or myopic degeneration of the posterior pole. We excluded vision-threatening diseases; however, the improvements in the UCVA and BCVA were significant, with favorable efficacy and safety indices (1.02 ± 0.56 and 1.31 ± 0.64, respectively) at postoperative month 1, in light of the refractive correction.

In the current study, 10.4% of cases had a postoperative IOP elevation, despite the exclusion of glaucomatous eyes. A recent study by Vargas et al. [20] that included 87 eyes did not report IOP elevations. Meire et al. reported that two of 38 cases had ocular hypertension [16], one of which with steroid-induced ocular hypertension resulted in the need for an additional trabeculectomy because the steroids could not be discontinued due to systemic oncologic treatment. This rate was relatively high compared to uncomplicated cataract surgeries [25–27]. The exact reason is unclear; however, more intense inflammation that resulted from iris manipulation to remove the pIOL may be a reason. In the current study, the IOPs of all the cases were controlled safely only with medications until postoperative month 1; however, surgeons must be alert to IOP elevation postoperatively.

The current study had some limitations, one of which was the absence of a control group. Considering the baseline ECD (1986 ± 732 cells/mm2) with an average patient age of 55.0 ± 7.5 years, the corneal endothelial damage was probably an important reason for the surgery. Therefore, other surgeries, such as standard cataract surgery or cataract surgeries for eyes with a posterior-chamber pIOL, were not considered as suitable controls because the indications differed. Despite this, we believe our data, comprised of the largest sample size of cataract surgery for eyes with pIOL, are valuable.

In the current study, the UCVA improved significantly from 0.29 ± 0.34 to 0.03 ± 0.19 at postoperative at month 1. The value at day 1 (0.11 ± 0.30) improved significantly from the preoperative level. However, the differences between the targeted and postoperative refractive errors were not assessed in this study. Although it was reported that the preoperative biometric measures were generally accurate [28], some miscalculations in the axial length were found along with the subsequent hyperopic change [29]. Furthermore, the types of inserted lens varied and included toric and multifocal IOLs because of the multicentre study. The targeted refractive error in most current cases was emmetropia or weak myopia (mean targeted refractive error, −0.17 ± 0.49) and the postoperative SE was −0.17 ± 0.84. Therefore, satisfactory outcomes were achieved in most cases; however, the specific analysis, such as the optimal IOL calculation formula to be used, will be addressed in our next study.

Our follow-up period was short. Although the recovery from the surgery was favorable despite this short follow-up period, the information about the clinical outcomes and safety with longer follow-up is essential for clinicians. In particular, the ECD significantly

decreased at 1 month after surgery. The explantation of pIOL was carefully performed through sclerocorneal incision in order to not touch the endothelium. This procedure specific to the surgery might have had an effect. However, the ordinary cataract surgery with phacoemulsification and IOL implantation is well known to have an effect on ECD. The ECD change in our study was, on average, 4.5%. This was comparable to the past study of ordinary cataract surgery [30,31]. Thus, the ECD change was relatively small, but the early endothelial cell change cannot be fully evaluated by ECD [32]. Although the number of cases will be limited due to the retrospective design, careful and longer follow-up is needed. This will be discussed in the near future.

In conclusion, cataract surgeries for patients with iris-fixated pIOL were performed safely with good visual outcomes. We believe this option may be considered for patients with a pIOL who have visual impairment and endothelial cell loss.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/10 .3390/jcm10163672/s1, Figure S1: Comparison of subjective astigmatism between the pIOL materials, Table S1: Intraocular lenses implanted during cataract surgery.

**Author Contributions:** Conceptualization, M.K.O., I.T., H.A., T.N. and K.N.; Data Curation, M.K.O., S.M., I.T., H.A., T.N. and K.N.; Formal analysis, M.K.O.; Investigation, M.K.O. and K.N.; Methodology, M.K.O. and K.N.; Profect administration, K.N.; Resources, H.T., S.M., I.T., T.N. and K.N.; Supervision, S.M., M.A., I.T., H.A., T.N., K.T. and K.N.; Visualization, M.K.O.; Writing—original draft, M.K.O.; Writing—review and editing, H.T., S.M., M.A., I.T., H.A., T.N., K.T. and K.N. All authors will be informed about each step of manuscript processing including submission, revision, revision reminder, etc. via emails from our system or assigned Assistant Editor. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Keio University (Protocol code; 20190278, date of approval; 2 February 2020).

**Informed Consent Statement:** All patients read and signed the written informed consent form at each institute before the surgery. Patient consent for participating in this study was waived and the opt-out approach was used according to the Ethical Guidelines for Medical and Health Research Involving Human Subjects presented by the Ministry of Education, Culture, Sports, Science and Technology in Japan.

**Data Availability Statement:** The data presented in this study are available on request from the corresponding author with the permission of the Keio University Ethics Committee. The data is stored, and it will be discarded after the approved period by Ethics Committee.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


### *Article* **The Effect of Ametropia on Glaucomatous Visual Field Loss**

**Eun Young Choi 1,2,3,†, Raymond C. S. Wong 1,2,†, Thuzar Thein 1,2, Louis R. Pasquale 4, Lucy Q. Shen 5, Mengyu Wang 1,2, Dian Li 1,2, Qingying Jin 1,6, Hui Wang 1,7, Neda Baniasadi 1, Michael V. Boland 8, Siamak Yousefi 9, Sarah R. Wellik 10, Carlos G. De Moraes 11, Jonathan S. Myers 12, Peter J. Bex <sup>13</sup> and Tobias Elze 1,2,\***


**Abstract:** Myopia has been discussed as a risk factor for glaucoma. In this study, we characterized the relationship between ametropia and patterns of visual field (VF) loss in glaucoma. Reliable automated VFs (SITA Standard 24-2) of 120,019 eyes from 70,495 patients were selected from five academic institutions. The pattern deviation (PD) at each VF location was modeled by linear regression with ametropia (defined as spherical equivalent (SE) starting from extreme high myopia), mean deviation (MD), and their interaction (SE × MD) as regressors. Myopia was associated with decreased PD at the paracentral and temporal VF locations, whereas hyperopia was associated with decreased PD at the Bjerrum and nasal step locations. The severity of VF loss modulated the effect of ametropia: with decreasing MD and SE, paracentral/nasal step regions became more depressed and Bjerrum/temporal regions less depressed. Increasing degree of myopia was positively correlated with VF depression at four central points, and the correlation became stronger with increasing VF loss severity. With worsening VF loss, myopes have increased VF depressions at the paracentral and nasal step regions, while hyperopes have increased depressions at the Bjerrum and temporal locations. Clinicians should be aware of these effects of ametropia when interpreting VF loss.

**Keywords:** glaucoma; ametropia; myopia; hyperopia; visual field; OCT; SITA standard 24-2; pattern deviation; mean deviation; spherical equivalent

#### **1. Introduction**

Glaucoma is an optic neuropathy characterized by progressive loss of retinal ganglion cells, resulting in optic nerve damage and eventual visual field (VF) loss. Since glaucoma

**Citation:** Choi, E.Y.; Wong, R.C.S.; Thein, T.; Pasquale, L.R.; Shen, L.Q.; Wang, M.; Li, D.; Jin, Q.; Wang, H.; Baniasadi, N.; et al. The Effect of Ametropia on Glaucomatous Visual Field Loss. *J. Clin. Med.* **2021**, *10*, 2796. https://doi.org/10.3390/jcm10132796

Academic Editor: Kazuno Negishi

Received: 1 June 2021 Accepted: 15 June 2021 Published: 25 June 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

tends to produce specific VF defects, the pattern deviation (PD) plot, which shows relative light sensitivity normalized by age-matched controls at each VF location, is crucial for the diagnosis of this optic neuropathy. Standard automated perimetry, particularly the Swedish interactive thresholding algorithm (SITA) standard 24-2 [1,2] is a widely used tool to characterize and monitor functional vision loss from glaucoma [3,4].

High myopia is considered a risk factor for glaucoma in several studies [5–7]. It is wellknown that refractive error is associated with ocular biometric features. In general, myopic eyes tend to have a longer axial length and are more prolate than emmetropic eyes, while hyperopic eyes tend to have a shorter axial length and are more oblate (Figure 1A) [8,9]. In addition, the superior and inferior arcuate retinal nerve fiber bundles lie closer to the fovea in myopes compared to emmetropes or hyperopes (Figure 1B), resulting in a thicker temporal peripapillary retinal nerve fiber layer (RNFL) in myopic eyes [10–13]. Previous studies have shown the association between the spherical equivalent (SE) of refractive error and various anatomical parameters of the optic nerve head (ONH), which serve as important diagnostic criteria for glaucoma [12,14,15]. For example, increasing myopia is associated with greater optic disc torsion and tilt [14,15]. Furthermore, we have previously shown that the central retinal vessel trunks (CRVT), where retinal vessels enter and exit the optic disc, are located more nasally in myopes compared to hyperopes [15]. The nasalization of CRVTs, in turn, has been correlated with a central pattern of VF loss [16–18]. These findings suggest that myopes and hyperopes, with their varying structural parameters, may also have different patterns of light sensitivity. Previous works show myopia to be a risk factor for paracentral VF defects in glaucomatous eyes [19–22], while others report a high incidence of temporal VF defects in highly myopic eyes without known glaucoma [23]. We sought to build upon these studies by systematically examining the interaction effect of the full range of ametropia and VF loss severity on global VF patterns. Our goal is to understand how functional vision is affected by ametropia in patients with glaucoma.

In this study, we investigate the relationship between ametropia and VF patterns utilizing a large VF dataset from 5 academic institutions. Furthermore, we study the role of VF loss severity in modulating this relationship. We hypothesize that (A) given the structural differences in the eye, ametropia is associated with distinct patterns of light sensitivity, regardless of glaucoma; (B) because myopes have retinal nerve fiber (RNF) bundles that lie closer to the fovea, there is an interaction effect between glaucoma severity and ametropia; and (C) because myopes have more nasalized CRVTs, they develop deeper central VF depression (Figure 1). Our study aims to help clinicians better identify and interpret glaucomatous VF loss patterns in myopic and hyperopic patients.

**Figure 1.** Schematic illustration of the three main hypotheses. (**A**) Ametropia is related to differences in eye length and shape, e.g., myopic eyes are longer, "curvier" (more prolate), and less regular. Therefore, we hypothesize relative differences of light sensitivity related to ametropia independent of glaucoma. (**B**) The two major retinal nerve fiber bundles, illustrated by dashed lines superimposed on the locations of a Humphrey 24-2 visual field (VF), are closer to the fovea for myopes (red lines) than for hyperopes (blue lines). Therefore, we hypothesize a center-periphery interaction effect between glaucoma severity and ametropia, schematically illustrated by the two different colors of the VF locations. (**C**) Myopia is correlated to a nasalization of the central retinal vessel trunk which, in turn, is related to glaucomatous central VF loss on the four central locations of the Humphrey 24-2 VF, illustrated in red. Therefore, we hypothesize deeper central VF depression for myopes, particularly for higher glaucoma severity.

#### **2. Methods**

The VFs used for this study were obtained through the Glaucoma Research Network, a multicenter consortium, which consists of Massachusetts Eye and Ear, Wilmer Eye Institute, New York Eye and Ear Infirmary, Wills Eye Hospital, and Bascom Palmer Eye Institute. The institutional review board of each participating institution approved this retrospective study. This study adheres to the Declaration of Helsinki and all federal and state laws.

#### *2.1. Participants and Data*

Our dataset consisted of SITA standard 24-2 VFs measured with the Humphrey Field Analyzer (HFA; Carl Zeiss Meditec, Dublin, CA, USA). The dataset used in this study consisted of all available VFs from the glaucoma services of Massachusetts Eye and Ear, Wilmer Eye Institute, New York Eye and Ear Infirmary, and Wills Eye Hospital, and the entire set of VF measurements from Bascom Palmer Eye Institute. The reliability criteria for VF selection were as follows: fixation losses ≤ 33%, false-negative rate ≤ 20%, and false-positive rate ≤ 20% [17,24–27]. If more than one measurement per eye fulfilled the reliability criteria, the most recent reliable VF was selected for each eye. VFs from the left eye were reflected along the vertical axis to match the orientation of the right eye, which is the standard orientation displayed in this paper. At testing time, the operator was required to enter the patient's distance refractive error into the HFA machine in order for the machine to determine the matching trial lens. These distance refractive error values were logged by the HFA and used in the present study. The HFA device automatically assigns a value of 0 to all participants wearing a contact lens; therefore, all eyes with a distance refractive error of 0 could not be distinguished whether they were naturally emmetropic, pseudophakic, and emmetropic due to successful cataract surgery, or corrected by contact lenses and thus were excluded from analysis. In our supplemental analyses, additional exclusion criteria were applied based on age, SE, and mean deviation (MD): patients younger than 18 years or older than 80 years, eyes with −1.5 D ≤ SE ≤ +1.0 D, and eyes with MD less than −18 dB were excluded.

#### *2.2. Statistical Analyses*

All statistical analyses were performed using the R platform [28]. For patients with minimal VF loss, defined as MD within ±1 dB, mean PD and their standard deviations were plotted against SE for each VF location on the Humphrey 24-2. Linear regression slopes of PD and SE were calculated and plotted for patients with MD within ±1 dB and for those with MD < −12 dB. Furthermore, PD values at each VF location were modeled by linear regression with SE, MD, and their interaction (SE × MD) as regressors, using the following equation: PD~SE + MD + (SE × MD). Finally, given our previous finding that CRVT nasalization was associated with VF loss in the central 4 VF locations [17], SE slopes were calculated for the 4 most central locations, as a function of the magnitude of MD. *p* values of the slopes were adjusted for multiple comparisons by the false discovery rate method [29]. A *p* value < 0.05 was considered statistically significant.

#### **3. Results**

A total of 120,019 VFs from 120,019 eyes of 70,495 patients met our inclusion criteria. Figure 2 summarizes the clinical and demographic information of the subjects.

In the analysis involving all eyes, MD had a weak but statistically significant correlation with SE (Pearson's r = 0.045, *<sup>p</sup>* < 2.2 × <sup>10</sup>−16). Figure <sup>3</sup> shows the mean PD values at each of the 52 VF locations, grouped by bins of SE (bin centers: −6, −4, −2, 0, 2, 4, and 6 Diopters (Ds), bin width: ±1 D), for individuals with minimal VF loss (MD within ±1 dB). The following general trend was observed: with increasing myopia (decreasing SE), PD values increased at the peripheral VF locations and decreased at the central VF locations; opposite effects were noted for hyperopia.

**Figure 2.** Demographic histograms of age, visual field mean deviation (MD), and spherical equivalent of refractive error (from top to bottom). Quartiles are denoted by vertical lines.

Given the generally monotonic pattern of correlation observed, linear regression of PD from SE was performed to quantify the relationship. The regression coefficients at each VF location are shown in Figure 4. For patients with minimal VF loss (MD within ±1 dB), positive coefficients were observed in the paracentral and temporal VFs, indicating that increased myopia was associated with decreased light sensitivity in these regions. Negative slopes were observed mostly in the Bjerrum and nasal step areas, indicating that increasing hyperopia was associated with lower light sensitivity in these regions (Figure 4A). These results were in line with the trend observed in Figure 3. The significant positive slopes ranged from 0.01 to 0.04, and significant negative slopes ranged from −0.01 to −0.11 (*p* < 0.05). This means that for individuals with at most mild glaucoma, high myopes (SE: −6 D) can have up to 0.48 dB lower and 1.3 dB higher PD values compared to high hyperopes (SE: +6 D) at individual VF locations.

**Figure 3.** Mean pattern deviations (PD), illustrated by filled circles, and corresponding standard deviations (whiskers) grouped by bins of spherical equivalent (SE) of refractive error (bin centers: −6, −4, −2, 0, 2, 4, and 6 Diopters) for each visual field (VF) location for patients with VF mean deviations within ±1 dB. Each SE bin contains SEs within ±1 Diopter of the respective bin center. The location of fixation is denoted by the central blue cross. The two VF locations closest to the blind spot are omitted.

For patients with severe VF depression (MD < −12 dB), the pattern was slightly different: positive slopes were observed mostly in the paracentral VF, and negative slopes were observed in the Bjerrum and temporal regions (Figure 4B). This implies that increasing myopia was associated with VF depression in the paracentral region, and increasing hyperopia was associated with depression in Bjerrum and temporal regions. The magnitudes of the slopes were greater for severe VF loss compared to mild VF loss: the significant positive slopes ranged from 0.01 to 0.19, and significant negative slopes ranged from −0.02 to −0.23 (*p* < 0.05). This means that for severe glaucoma, high myopes (SE: −6 D) can have up to 2.3 dB lower and 2.8 dB higher PD values than high hyperopes (SE: +6 D) at individual VF locations.

To further explore the relationship between SE and PD, and to understand the role of VF loss severity on this correlation, linear regression was carried out with SE, MD, and their interaction term (SE × MD) as regressors. Figure 5A shows the "pure" SE effect on PD: when MD was not taken into account, myopes had a significantly lower light sensitivity in the paracentral and temporal VFs, but greater light sensitivity in the Bjerrum and nasal step regions. When the interactive effect of MD and SE was examined, myopic VF depression became localized to the paracentral and nasal step regions while hyperopic VF depression became more pronounced at the Bjerrum and temporal areas (Figure 5B). The significant positive interaction coefficients ranged from 0.002 to 0.012, and significant negative coefficients ranged from −0.002 to −0.01 (*p* < 0.05). The detailed regression coefficients for SE, MD, and SE × MD at each of the 52 VF locations are provided

in Supplementary Materials Figure S1. As expected, the effect of MD alone on PD showed a highly significant correlation at every location.



**Figure 4.** Spherical equivalent regression coefficients of pattern deviations at each visual field (VF) location for (**A**) patients with (at most) minor VF depression (mean deviation (MD) within ±1 dB) vs. (**B**) patients with severe VF depression (MD < −12 dB). Non-significant coefficients are colored in black, significant positive coefficients in red, and significant negative coefficients in blue. In short, at red/blue locations, myopes have more/less VF depression.

**Figure 5.** (**A**) Impact of spherical equivalent (SE) on visual field pattern deviations that are not explained by glaucoma severity (mean deviation, MD) and (**B**) interaction effects between glaucoma severity (MD) and SE. Significant locations are denoted by filled squares, non-significant locations by small, open squares. In label (**A**), red/blue locations denote positive/negative coefficients, i.e., locations where myopes have more/less VF depression regardless of glaucoma severity. In label (**B**), red/blue locations denote negative/positive coefficients of the interaction term (SE × MD). In short, at red/blue locations, increasing glaucoma severity is related to more/less VF depression in myopes.

Example VFs of myopic and hyperopic patients seen at Mass. Eye and Ear displaying these VF loss patterns are shown in Figure 6. With worsening glaucoma, myopic individuals tend to develop deeper paracentral VF defects, while hyperopic individuals tend to develop greater VF depression in the Bjerrum and temporal regions.

Finally, we examined the effect of SE on PD at the 4 most central VF locations (marked by the red squares in Figure 1C) as a function of VF loss severity. Myopia was significantly correlated with decreasing PD values at the central 4 locations (*p* < 0.001), and the correlation became stronger with decreasing MD (Table 1).

**Figure 6.** Example visual fields (VFs) of myopic and hyperopic patients with glaucoma, and the progression of VFs over time. Total deviation (TD) plots are shown for each patient: the color plots represent the numerical TD values (dB) and the grayscale plots represent the probability plots. In myopic patients (left panel), VF defects tend to be located in the paracentral and nasal step regions, whereas in hyperopic patients (right panel), VF defects tend to be located in the Bjerrum and temporal regions.

**Table 1.** Spherical equivalent regression coefficients of pattern deviations for the central four visual field (VF) locations on SITA 24-2 by VF loss severity. Each mean deviation (MD) bin contains MDs within ±3 dB of the respective bin center given in the first column. *p* values are adjusted for multiple comparisons.


#### **4. Discussion**

In this study, we systematically investigated and quantified the effect of ametropia on retinal sensitivity at each VF location in the 24-2 pattern. While effects of myopia on specific VF defects have been reported [19–23], to our best knowledge, no prior work has examined this relationship in detail over the full range of ametropia and over the entire VF test locations. Additionally, we studied the interactive effect of ametropia and glaucoma severity on VF loss patterns. Our results show that while the effects of ametropia on individual PD values are small, there are distinct patterns of VF loss associated with myopia and hyperopia, and the relationship becomes stronger with increasing VF loss severity.

The Glaucoma Research Network dataset does not contain ophthalmic diagnoses, but given the origins of this large dataset, we may safely assume that VF loss occurring in these patients is mostly due to glaucoma. We first hypothesized that because of the structural variations in myopic and hyperopic eyes [8,9], there would be differences in light sensitivity depending on the degree of ametropia, regardless of the presence of VF loss. We demonstrate that in patients with minimal VF loss, patterns of light sensitivity differ among myopes and hyperopes, with myopes having relatively decreased sensitivity in the paracentral and temporal VF areas and hyperopes in the Bjerrum region and nasal step areas (Figure 4A). Notably, the different patterns in Figure 4A,B indicate a possibly independent effect of ametropia from that of nerve fiber anatomy associated with ametropia on VF loss. Therefore, we chose to statistically disentangle these two effects. Figure 5A shows the "pure SE effect", i.e., the effect without accounting for the variance explained by VF loss severity. As expected, a pattern similar to Figure 4A is seen, with myopes having decreased sensitivity in the paracentral, inferior Bjerrum, and temporal areas. These "pure SE effects" could originate from ocular anatomical parameters associated with (axial) ametropia, but could also result from lens related diseases (e.g., nuclear cataract) or even by trial lens related measurement artifacts. Without medical diagnoses, potentially confounding diseases could not be controlled for in the current study. In a previous work on high myopia, Ohno-Matsui et al. [23]. carefully controlled for diseases and excluded trial lens artifacts by applying soft contact lenses for perimetry. They studied 492 highly myopic eyes without known glaucoma: among the eyes with significant VF defects, temporal field defects were observed in 61.5% of the eyes with round discs, 75.0% of the eyes with vertically oval discs, and 68.2% of the eyes with obliquely oval discs. Consistent with their results, our study found the temporal field to be the dominant location of reduced sensitivity in myopia. While they focus only on extremely myopic patients, we examine the full range of ametropia and show that myopic and hyperopic individuals, regardless of VF loss severity, have distinct patterns of light sensitivity.

We also hypothesized that, given the anatomical differences in RNF bundle trajectories between myopic and hyperopic eyes, there would be an interaction effect of ametropia and glaucoma severity on VF patterns. As mentioned above, using linear modeling with the interaction term (SE × MD) as a regressor, we were able to disentangle the effect of SE from that of MD. Lens artifacts and diseases of the anterior segment such as cataracts are most likely additive to VF loss patterns but would not interact with glaucomatous VF loss severity. This means, the "pure SE effect" bundles all possibly artifactual lens effects and confounding diseases so that our SE × MD interaction results can likely be solely explained by retinal differences associated with ametropia, such as differences in nerve fiber anatomy. We demonstrate that with increasing severity of VF loss and degree of ametropia, myopes develop more profound paracentral and nasal step VF depressions, while hyperopes develop more depression in the Bjerrum and temporal VF points (Figures 4B and 5B). Furthermore, while myopia alone is associated with decreased sensitivity in the temporal sector and increased sensitivity in the nasal step sector, the pattern reverses when the interactive effect of ametropia and VF loss severity is examined. These distinct patterns indicate that different mechanisms are responsible for the effects of ametropia and glaucoma on VF loss.

We performed additional analyses after excluding subjects older than 80 years or younger than 18 years, as these patients might have a higher ratio of non-excluded pseudophakia (see Discussion) or not have age-matched controls, respectively. Similar effects on VF patterns were observed with or without the age exclusion criteria (Supplementary Materials Figure S2). Furthermore, we performed analyses after excluding eyes with

MD < −18 dB, because our dataset and others indicate that the pattern standard deviation and PD values begin to normalize at this degree of VF loss severity [30]. Again, similar effects were observed with this exclusion criterion (Supplementary Materials Figure S3), indicating that our results are not caused by potential non-linearities of the PD values. Finally, we re-analyzed the data after excluding eyes with lower absolute refractive error (−1.5 D ≤ SE ≤ +1.0 D) to exclude the vast majority of pseudophakics (see Discussion). Similar results were obtained with this exclusion criterion as well (Supplementary Materials Figure S4).

Given our findings, we further examined the effect of ametropia on light sensitivity at the 4 most central VF locations on the 24-2 plot representing macular function. This experimental design was inspired by our previous work [17] showing that CRVT nasalization was significantly correlated with VF depression only in the central sector (as defined by the annular scheme [17] and the Garway-Heath scheme [31]). In the current study, we demonstrate that myopia is significantly associated with VF loss in the central four locations and that the correlation becomes progressively stronger with increasing VF loss severity (Table 1). These results are consistent with our previous finding that myopes have more nasally located CRVTs [15], which in turn is associated with deeper central VF depression [16,17]. Although we cannot conclude any causal relationships, CRVT nasalization may explain the increased susceptibility of myopic eyes to central VF loss. We and others have speculated that CRVTs can act as stabilizing forces against glaucomatous deformation of the lamina cribrosa [17]. More nasally located CRVTs in myopic eyes can result in greater mechanical strain in the temporal area, making the macular region more susceptible to glaucomatous damage.

Our finding that myopic individuals are predisposed to central vision loss is consistent with previous studies showing an association between myopia and paracentral scotomas [19–22]. Mayama et al. focusing on the central 12 points on HFA 30-2 VFs of 313 glaucoma patients, reported that myopia is associated with damage in the lower cecocentral VF [19]. Myopia was also found to be a risk factor for VF progression in the upper paracentral subfield in 92 normal-tension glaucoma patients [20]. In a recent study, Dias et al. found myopia to be associated with the presence of parafoveal scotomas in 130 glaucomatous eyes with disc hemorrhage [21]. The current study agrees with these prior works and significantly expands upon them by analyzing a dataset of over 120,000 VFs pointwise, rather than focusing only on the presence of paracentral scotomas or a subset of VF locations. Using this systematic approach, we show that myopic VF depression not only affects the cecocentral and paracentral areas but also extends to the nasal step locations, forming an arcuate pattern that corresponds to the superior and inferior arcuate bundle trajectories. Our results support the recommendations from previous studies that myopic individuals, particularly those with high myopia, deserve closer monitoring for central field defects which are highly correlated with quality of life [32,33].

While our study does not provide direct mechanistic evidence, we briefly discuss potential physiologic explanations for the VF patterns observed. First, the effect of SE alone on VF light sensitivity is likely due to structural differences between myopic and hyperopic eyes. Myopia is associated with increased axial length, optic disc tilt, and torsion [8,9,12,15,34]. Furthermore, structural parameters such as optic disc torsion [35] and abrupt change in scleral curvature [23] have been associated with VF defects in myopic eyes. The stretching or bending of optic nerve fibers due to mechanical tension may explain the increased susceptibility of myopic eyes to develop VF loss at certain locations. On the other hand, the VF patterns seen from the interaction of ametropia and glaucoma suggest that differences in RNF anatomy are responsible for the effect. The major superotemporal and inferotemporal RNF bundles, i.e., the arcuate fibers, are particularly susceptible to damage and are preferentially lost in glaucoma [36,37]. These bundles lie closer to the fovea in myopic eyes, as shown as a schematic in Figure 1B [10–13]. The reciprocal patterns observed, in which myopic VF loss shifts centrally and nasally with worsening glaucoma and hyperopic VF loss occurs in the opposite direction, correspond well to the respective locations of the arcuate fiber trajectories in myopic and hyperopic eyes.

In the present study, ametropia was significantly correlated to VF loss severity, but the effect was weak (*r* = 0.045). This likely represents a clinically insignificant result, in line with our previous study of a smaller population (*n* = 438) showing no significant association between SE and MD [15]. Our recent studies have shown, however, that optic nerve related parameters associated with myopia have specific impacts on the abnormality patterns of RNFL thickness measured by optical coherence tomography (OCT) [13,38]. Consistent with these findings, the current study shows differences in the patterns of relative light sensitivity between myopes and hyperopes, resulting in an effect modification of glaucomatous VF loss. Indeed, the magnitude of ametropia's effect on individual PD values was small, and we would not expect ametropia alone to produce VF loss that mimics glaucoma. However, the overarching patterns of VF loss indicate that there are distinct zones of vulnerability in myopic and hyperopic eyes predisposing them to different patterns of VF loss. These patterns are exemplified in Figure 6 showing VF progression in myopic and hyperopic glaucoma patients.

There are several strengths of our study: first, we used a large sample size of over 120,000 eyes collected from multiple institutions to study the effect of ametropia on visual function. Second, we used a systematic and quantitative approach to examine the effect of the full spectrum of SE pointwise over the entire 24-2 VF, quantifying the effect of SE on PD values at each VF location. Finally, our study focuses on the interaction term (SE × MD) in the regression analysis, separating the effect of ametropia from that of VF loss severity. This specific study design addresses well-known challenges related to research on myopia and posterior eye diseases, as it filters out the various potential impacts of refractive error on the VF and allows to extract only those effects that are immediately relevant for glaucoma.

This study also has several limitations. First, because of the retrospective, crosssectional nature of our study, we could establish associations between ametropia and VF patterns, but not causal relationships. Second, because axial length was not recorded by the HFA device, we used SE as an alternative. Third, in the absence of diagnostic information in our dataset, patients with lens related conditions could not be excluded from analysis. This is of particular relevance for cases of pseudophakia due to cataract surgery, which is a confounder when investigating impacts of ametropia on posterior eye diseases. We addressed this potential problem in two ways. First, as the prevalence of cataracts strongly increases with age, in a supplemental analysis we recalculated our results with subjects older than 80 years excluded. Second, in another supplemental analysis, we excluded all eyes with relatively mild refractive errors (−1.5 D ≤ SE ≤ +1.0 D), which is a range into which the vast majority of eyes fall after cataract surgery [39]. For either of these two additional data analyses, the effects we found were similar to the original results and did not change any of our conclusions. Apart from pseudophakia, we would like to note again that our focus on the SE×MD interaction term would extract most lens related properties as those are likely additive to VF loss patterns but would not be expected to interact with glaucomatous VF loss severity. Fourth, this study was restricted to the 24-2 pattern test. The 10-2 VF test has higher sensitivity for central vision compared to the 24-2 [40] and may be better suited to examine the detailed pattern of central VF loss. Fifth, a linear association between SE and PD was observed at most, but not all, of the VF locations (Figure 3). Nonlinear regression may be used in future studies to better model the association. Finally, the current study focused on functional data (VFs) and not structural data (e.g., RNFL defects on OCT), so we could only speculate the anatomical basis of the observed VF patterns. Future work will focus on characterizing the structure-function relationship and the effect of ametropia on this relationship.

In conclusion, utilizing a large dataset of over 120,000 VFs, we characterized the effect of ametropia on the spatial pattern of VF loss as a function of glaucoma severity. We demonstrate that myopic and hyperopic individuals are predisposed to developing different patterns of VF loss. With worsening VF loss severity, individuals with myopia

have increased depressions at the paracentral and nasal step regions; conversely, hyperopes have increased depressions in the Bjerrum and temporal regions. Clinicians should be aware of these effects from ametropia and take them into account when interpreting VF loss, particularly in patients with severe VF depression.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/ 10.3390/jcm10132796/s1, Figure S1: Regression coefficients for each of the 52 visual field locations; Figure S2: Impact of spherical equivalent (SE) on visual field pattern deviations that is not explained by glaucoma severity (mean deviation, MD), excluding age larger than 80 years old; Figure S3: Impact of spherical equivalent (SE) on visual field pattern deviations that is not explained by glaucoma severity (mean deviation, MD), for MD less than −18 dB; Figure S4: Impact of spherical equivalent (SE) on visual field pattern deviations that is not explained by glaucoma severity (mean deviation, MD),excluding lower refractive error.

**Author Contributions:** E.Y.C. and T.E. designed the study. E.Y.C., R.C.S.W. and T.E. analyzed the data and wrote the paper. E.Y.C., R.C.S.W., T.T., L.R.P., L.Q.S., M.W., D.L., Q.J., H.W., N.B., M.V.B., S.Y., S.R.W., C.G.D.M., J.S.M., P.J.B., T.E. collected data from their associated institutions, discussed the results and commented on the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by NIH R21EY030142 (T.E., S.Y.), NIH R21EY030631 (T.E.), NIH R01EY030575 (T.E.), NIH R01EY015473 (L.R.P.), BrightFocus Foundation (M.W., T.E.), Lions Foundation (M.W., T.E.), Grimshaw-Gudewicz Foundation (M.W., T.E.), Research to Prevent Blindness (M.W., T.E.), NIH K99EY028631 (M.W.), Harvard Glaucoma Center of Excellence (M.W., T.E., L.Q.S.), the Eleanor and Miles Shore Fellowship (L.Q.S.), Departmental Grant from Research to Prevent Blindness (C.G.D.M.), NIH R01EY025253 (C.G.D.M.), the Alice Adler Fellowship (T.E.), and NIH NEI Core Grant P30EY003790 (E.Y.C., M.W., T.E., D.L., H.W., Q.J.).

**Institutional Review Board Statement:** The study was approved by the Mass. Eye and Ear Institutional Review Board (Protocol #: 2019P000936).

**Informed Consent Statement:** As only retrospective and fully de-identified data were used, the Mass. Eye and Ear Institutional Review Board waived the need for informed consent.

**Data Availability Statement:** The datasets and analysis programs are available from the corresponding author.

**Conflicts of Interest:** Tobias Elze: US patent PCT/US2014/052414. Tobias Elze and Mengyu Wang: US provisional patents 62/804,903, 62/909,386, 62/637,181. Nothing to report for any other author.

#### **References**


### *Article* **Multifocal Femto-PresbyLASIK in Pseudophakic Eyes**

**Bojan Pajic 1,2,3,4,5,\*, Horace Massa 3, Philipp B. Baenninger 6, Erika Eskina 7,8, Brigitte Pajic-Eggspuehler 1, Mirko Resan <sup>5</sup> and Zeljka Cvejic <sup>2</sup>**


**Abstract:** Background: Presbyopia treatment in pseudophakic patients with a monofocal IOL is challenging. This study investigates the refractive results of femto-PresbyLASIK and analyzes presbyopia treatment in pseudophakic eyes. Methods: 14 patients with 28 pseudophakic eyes were treated with femto-PresbyLASIK. The dominant eye was targeted at a distance and the non-dominant eye at −0.5 D. The presbyopic algorithm creates a steepness in the cornea center by using an excimer laser that leads to corneal multifocality. Results: 6 months after surgery a refraction of −0.11 ± 0.13 D (*p* = 0.001), an uncorrected distance visual acuity of 0.05 ± 1.0 logMAR (*p* < 0.001) and an uncorrected near visual acuity of 0.15 ± 0.89 logMAR (*p* = 0.001) were achieved in the dominant eye. For the non-dominant eye, the refraction was −0.28 ± 0.22 D (*p* = 0.002), the uncorrected distance of visual acuity was 0.1 ± 1.49 logMAR, and the uncorrected near visual acuity was 0.11 ± 0.80 logMAR (*p* < 0.001). Spherical aberrations (Z400) were reduced by 0.21–0.3 μm in 32% of eyes, and by 0.31–0.4 μm in 26% of eyes. Conclusion: By steepening the central cornea while maintaining spherical aberrations within acceptable limits, PresbyLASIK created a corneal multifocality that safely improved near vision in both eyes. Thus, femto-PresbyLASIK can be used to treat presbyopia in pseudophakic eyes without performing intraocular surgery.

**Keywords:** presbyLASIK; excimer laser; multifocality; pseudophakic

#### **1. Introduction**

While patients are increasingly aware of the possibility that they do not need to wear spectacles after cataract surgery, if they have a simultaneous multifocal intraocular lens (IOL) placed, few patients are benefiting from this advanced technology. Indeed, the vast majority of patients are choosing a monofocal IOL. Limitations to the wider use of multifocal IOL might be their high cost, the careful patient selection that is required for good outcomes, or the patients' fear of side effects. Monofocal IOL placement after cataract surgery allows perfect vision, but only at one focal distance. This monovision can lead to patient dissatisfaction, and a desire to regain multifocality without corrective lenses. Unfortunately, solutions to restore multifocality remain scarce and poorly explored.

There are different ways to reach multifocality. The goal is to achieve the best possible visual outcome while maintaining a low level of optical disturbance. There are only 3

**Citation:** Pajic, B.; Massa, H.; Baenninger, P.B.; Eskina, E.; Pajic-Eggspuehler, B.; Resan, M.; Cvejic, Z. Multifocal Femto-PresbyLASIK in Pseudophakic Eyes. *J. Clin. Med.* **2021**, *10*, 2282. https://doi.org/10.3390/jcm10112282

Academic Editor: Kazuno Negishi

Received: 11 April 2021 Accepted: 21 May 2021 Published: 25 May 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

surgical options to treat presbyopia [1]. One option is to exchange the monofocal lens with a multifocal one, but this remains challenging, as treated eyes might be weakened by the first surgery. Thus, this does not have a high level of safety [2]. A second option would be the implantation of a multifocal add-on IOL [3], but this has several limitations. The power calculations of lenses are not as precise as with a laser. Deposits in the interface between the IOL in the bag and the add-on IOL might also disturb the vision. The rubbing of the add-on IOL against the iris tissues might induce ocular inflammation [4], or a pigment dispersion syndrome that risks elevated intraocular pressure and glaucoma. Lastly, this is an intraocular procedure that poses a certain amount of complication risk. The third option is to obtain multifocality at the corneal level. The concept of multifocal PresbyLASIK is an attractive correction method, because the surgical technique is based on the LASIK method. In contrast to a multifocal IOL implantation, minimal invasive surgery is necessary, because the eye does not need to be opened up. PresbyLASIK involves two steps. The first step is to correct ametropia for distance vision, and the second step is to make an addition for near vision. In multifocality, the central part of the cornea is most often adjusted for proximity, and the middle periphery is corrected for distance [5–10].

A conventional PresbyLASIK always represents a compromise between distance and near vision, since it creates unwanted aberrations, especially spherical aberrations in the central pupillary region. To minimize unwanted aberrations, today's PresbyLASIK treatment algorithms are wavefront-guided. Compared to the well-established treatment of presbyopia with a multifocal IOL, PresbyLASIK is a newer surgical technique, but it has the advantage of being less invasive than implanting an IOL, because the eye does not need to be opened up. On the other hand, the use of PresbyLASIK is much more demanding. Patient selection and the interpretation of objective preoperative topographic and wavefront analyses are challenging. In particular, decisions based on the Zernike polynomial analysis of the cornea have a high influence on the surgical result.

It is not sufficient to use the general LASIK criteria for PresbyLASIK application. The lack of encouraging treatment results of PresbyLASIK to date is likely because the indication for surgery was on LASIK criteria, and corresponding refraction and other parameters from the wavefront analysis were not taken into account [11]. Moreover, even if wavefront analysis is done perfectly, it must be adapted to pupillary diameter in the mesopic condition [12].

The PresbyLASIK, in particular the Supracor algorithm, was already successfully used with presbyopic phakic eyes [11,13,14]. Therefore, in this retrospective study, we assessed refractive outcomes after PresbyLASIK in pseudophakic patients.

#### **2. Materials and Methods**

We included 14 patients with 28 pseudophakic eyes in this retrospective case series. The same surgeon performed all surgical procedures. The study was approved by the Ethics Committee in Novi Sad (34–08.18). This study was conducted in accordance with the Protocol, the Declaration of Helsinki, and all applicable regulatory requirements.

In the following Table 1, all significant preoperative PresbyLASIK data were listed of all 14 patients, such as mean age, UDVA, CDVA, UNVA, CNVA for the dominant and non-dominant eye, as well as the refraction preoperative levels for the dominant and nondominant eyes. The mean period between cataract surgery and presbyopia was 8.93 ± 3.82 (range 6–16) months (Table 1).


**Table 1.** Details regarding preoperative data prior to PresbyLASIK, inclusive preoperative refraction, visual acuity in logMAR, and time elapsed since cataract surgery in months.

Inclusion criteria were a dissatisfaction with myopic refraction obtained with a monofocal IOL with manifest refraction spherical equivalent (MRSE) between −0.5 and −4.0 diopters (D), astigmatism of 2.50 D or less, mean keratometry between 41.00 and 46.00 D, a central corneal thickness of 540 μm or more, a mesopic pupil diameter between 4 and 6 mm, and a kappa angle of less than 6◦. Exclusion criteria were the presence of ocular surface disease, clinically significant corneal opacity, posterior segment ocular pathologies, and abnormal corneal topography. All pseudophakic patients received the same IOL (Nidek NS 60YG, Nidek CO. LTD., Gamagori, Japan) during the cataract surgery.

All patients had a complete ophthalmologic examination prior to surgery, including manifest refraction, cycloplegic refraction, slit lamp microscopy of the anterior ocular segment, dilated fundoscopy and intraocular pressure measurement. The preoperative examination also included corneal topography with the Orbscan II system (Technolas Perfect Vision GmbH, Munich, Germany) and Pentacam (Oculus optical devices, Wetzlar, Germany). Wavefront aberrometry measurements were performed preoperatively with the Zywave II aberrometer (Technolas Perfect Vision GmbH) with undilated pupils and pupillometry. Eye dominance was determined by means of a "hole test". The measurement was carried out under scotopic conditions. The aberration analysis was carried out in a 6-mm zone.

Uncorrected near (UNVA) and distance (UDVA) visual acuity, and corrected near (CNVA) and distance (CDVA) visual acuity, were assessed using Snellen visual charts for distance vision and the Jaeger Scale for near vision, and then converted into a logarithm of the minimum angle of resolution (logMAR) notation. In all examinations, the eyes were not dilated. The examinations were performed at baseline, then postoperatively at 1 week, 1 month, 3 months and 6 months. Bilateral LASIK multifocal aspheric corneal ablation treatment was performed at least 6 months after cataract surgery.

The procedures were completed using the Supracor PresbyLASIK algorithm with a Teneo 317 excimer laser (Technolas Perfect Vision GmbH, Munich, Germany). The dominant eye of the patient was planned as plano for distance, while the non-dominant eye was slightly aimed at myopia of −0.5 D. However, we simulated the desired postoperative outcome before surgery using a contact lens. In the 14 patients included in the study, the distance setting was considered comfortable for the dominant eye. The LASIK incision was

performed using a femtosecond laser (Ziemer Ophthalmic Systems, LDV, Port, Switzerland) with a target flap thickness of 110 μm. The hinge was set superior in each case, with a flap diameter of 9.5 mm.

Our presbyLASIK protocol included a treatment algorithm with 2 phases. In the first phase, the dominant eye is treated for emmetropia and the non-dominant eye to aim for −0.5 diopters myopia with the excimer laser. The Munnerlyn formula [15] was used to determine the feasibility of the ablative process. In a second phase, but in the same treatment, a central steepness is achieved by ablation in a 3–6 mm zone and, in principle, is an addition for near vision. A multifocality is created in the cornea, which seamlessly represents a correction for near, intermediate and distance vision (Figure 1). Multifocality was created in both treated eyes during PresbyLASIK. To counteract the spherical aberration induced by this multifocal treatment, the laser applied additional wavefront-guided correction.

**Figure 1.** Topographical imaging showing a central steepness of the cornea created using the Supracor PresbyLASIK algorithm.

This wavefront-guided correction reduces higher-order aberrations (HOA), as shown by the point spread function (PSF). It can be qualitatively appreciated in a patient example of how the PSF was significantly reduced after wavefront-guided presbyLASIK (Figure 2). The focus was mainly on the correction of spherical aberration.

The postoperative topical regime was Tobradex (Alcon Laboratories, Inc., Fort Worth, TX, USA) 3 times daily for seven days, and topical hyaluronic acid 0.15% 3 times daily for a month.

Statistical analysis was performed using the IBM SPSS Statistics version 22.0 (IBM Corp., Armonk, NY, USA). The Kolmogorov–Smirnov and Shapiro–Wilk tests were used to test the data sets for normal distribution. If *p* > 0.05, the data set was considered normally distributed. If the data sets were parametric, they were calculated using the Pearson normality test, an unpaired t-test and ANOVA test. For the non-parametric data sets, the Friedmann test was used for further analysis. Significance was considered to be when *p* < 0.05.

**Figure 2.** Reduction of PSF after wavefront-guided presbyLASIK.

#### **3. Results**

A total of 28 eyes in 14 patients were treated, of which 9 (64%) were female and 5 (36%) were male. The mean age was 56 ± 13 years. Mean preoperative MRSE was −1.43 ± 1.03 D (range: −0.50 to −3.0 D), mean sphere −0.87 ± 0.81 D (range: −2.00 to 0.25 D) and mean cylinder −1.13 ± 0.73 D (range: 0.00 to −2.00 D). The mean preoperative monocular CDVA was 0.1 ± 0.85 logMAR (Snellen) and the CNVA, 0.19 ± 0.82 logMAR (Jaeger 5).

#### *3.1. Dominant Eye*

#### 3.1.1. Refraction

The mean preoperative refraction in the dominant eye was −1.63 ± 1.03 D. Distance adjustment was aimed for emmetropia. The mean postoperative refraction was −0.04 ± 0.29 D, 0.01 ± 0.28 D and −0.11 ± 0.13 D after 1, 3 and 6 months, respectively (Figure 3). Refraction significantly improved from preoperative testing to 1-month postoperative testing (*p* = 0.001), without further significant changes at later times (*p* = 0.37) and (*p* = 0.42).

**Figure 3.** Stability: Change in refraction over time in the dominant eye.

#### 3.1.2. Distance Vision

At the 1-week postoperative test, 93% of eyes had a UDVA better than 0.2 logMAR, while the remainder had better than 0.3 logMAR. At 1 month after surgery, 50% of eyes had a UDVA of 0.1 logMAR, 36% had a UDVA of 0.2 logMAR, and the remainder (14%) had a UDVA of 0.3 logMAR. These same percentages persisted at 3 months, postoperatively (50%, UDVA of 0.1 logMAR; 36%, 0.2 logMAR; 14%, 0.3 logMAR. At 6 months, postoperatively, 57% of eyes had UDVA of 0.0 logMAR and the remainder of eyes (43%) had a 0.1 logMAR (Figure 4). Preoperative UDVA was 0.42 ± 1.15 logMAR and increased to 0.14 ± 1.05 logMAR, 0.21 ± 1.10 logMAR, 0.07 ± 1.05 and 0.05 ± 1.00 logMAR 1 week, 1 month, 3 and 6 months postoperatively, respectively. Compared to the preoperative value, the increase to each postoperative value was significant (*p* < 0.001). Visual acuity significantly increased between the first postoperative week and the third postoperative month (*p* = 0.014) and from the first postoperative month to the third postoperative month (*p* = 0.017).

**Figure 4.** Uncorrected distance visual acuity percentage distribution.

The mean CDVA was 0.10 ± 0.89 logMAR preoperatively. CDVA fluctuated from 0.12 ± 0.83 logMAR at 1 week postoperatively, 0.14 ± 1.05 logMAR at 1 month postoperatively, 0.05 ± 1.0 logMAR at 3 months postoperatively, to 0.03 ± 1.05 logMAR at 6 months postoperatively. CDVA increased significantly from preoperative values to those obtained at 3 months (*p* = 0.027) and 6 months (*p* = 0.003), postoperatively. There was also a significant increase in CDVA from the first postoperative week to the third postoperative month (*p* = 0.003), and the sixth postoperative month (*p* < 0.001). CDVA also significantly increased from the first postoperative month to the third postoperative month (*p* < 0.001) and to the sixth postoperative month (*p* < 0.001). There was no significant change in CDVA after the third postoperative month.

CDVA was also assessed in terms of safety. At 1 week postoperatively, CDVA was unchanged in 71% of eyes, while 29% lost 1 line of CDVA. At 1 month postoperatively, CDVA was unchanged in 71% of eyes, but 14% lost 1 or 2 lines of CDVA, respectively. At 3 months postoperatively, CDVA was unchanged in 50% of eyes, while the other half gained 1 line. By 6 months, 21% of eyes had unchanged CDVA and 79% gained 1 line (Figure 5).

**Figure 5.** Safety: Changes in corrected distance visual acuity over time compared to preoperative values.

The cumulative CDVA at 1 week postoperatively was 0.3 logMAR or better in all eyes, 0.2 logMAR or better in 93%, 0.1 logMAR or better in 50%, and 0 logMAR or better in 7% of eyes. At 1 month postoperatively, CDVA was 0.3 logMAR or better in all eyes, 0.2 logMAR or better in 86% and 0.1 logMAR or better in 50%. At 3 months postoperatively, CDVA was already 0.1 logMAR or better in all eyes, and 29% had CDVA of 0 logMAR or better. At 6 months postoperatively, all eyes had a 0.1 logMAR or better and 57% had a CDVA of 0 logMAR or better (Figure 6).

**Figure 6.** Cumulative corrected distance visual acuity.

The cumulative UDVA at 1 week postoperatively was 0.3 logMAR or better in all eyes, 0.2 logMAR or better in 93% of eyes, and 0.1 logMAR or better in 50% of eyes. One month postoperatively, UDVA was 0.3 logMAR or better in all eyes, 0.2 logMAR or better in 93% of eyes and 0.1 logMAR or better in 7% of eyes. Three months postoperatively, UDVA was already 0.2 logMAR or better in all eyes, 93% of eyes had UDVA of 0.1 logMAR or better and 21% of eyes had UDVA of 0 logMAR. At 6 months postoperatively, all eyes had a 0.1 logMAR or better and 57% of eyes had a UDVA of 0 logMAR or better (Figure 7).

**Figure 7.** Cumulative uncorrected distance visual acuity.

#### 3.1.3. Near Vision

The mean preoperative UNVA was 0.46 ± 1.0 logMAR. At 1 week postoperatively UNVA increased to 0.13 ± 0.77 logMAR, 1 month postoperatively to 0.09 ± 0.89 log-MAR, 3 months postoperatively to 0.14 ± 0.89 logMAR and 6 months postoperatively to 0.15 ± 0.89 logMAR. The difference in UNVA was significant at each time point compared to preoperative values (*p* < 0.001).

The CNVA was 0.19 ± 0.80 logMAR preoperative. One week postoperatively, there was a slight visual improvement to 0.10 ± 0.89 logMAR, 1 month postoperatively to 0.08 ± 1.04 logMAR, 3 months postoperatively 0.10 ± 1.0 logMAR and 6 months postoperatively to 0.10 ± 0.96 logMAR. Visual acuity only increased significantly between the preoperative values and 1 month postoperatively (*p* = 0.007). Otherwise, there was no other significant improvement compared to preoperative values (*p* > 0.05).

#### *3.2. Non-Dominant Eye*

#### 3.2.1. Refraction

The refraction target value was set at −0.5 D. The mean preoperative refraction was −1.23 ± 1.03 D, −0.29 ± 0.35 D at 1 month postoperatively, −0.26 ± 0.32 D at 3 months postoperatively and −0.28 ± 0.22 D at 6 months postoperatively. Refraction significantly changed at 1 month (*p* = 0.001), 3 months (*p* = 0.004) and 6 months (*p* = 0.002), compared to preoperative values (Figure 8).

**Figure 8.** Stability: Change in refraction over time in the non-dominant eye.

#### 3.2.2. Distance Vision

At 1 week postoperatively, 7% of eyes had an uncorrected distance visual acuity (UDVA) of 0 logMAR, 21% of 0.1 logMAR, 50% of 0.2 logMAR and 21% of 0.3 logMAR, respectively. By 1 month after surgery, 14% of eyes had a UDVA of 0.1 logMAR and 86% had a UDVA of 0.2 logMAR. At 3 months postoperatively, 71% of eyes had a UDVA of 0.1 logMAR and 29% of 0.2 logMAR. Six months postoperatively, 14% had a UDVA of 0 logMAR and 86% of 0.1 logMAR (Figure 9). The mean UDVA was 0.33 ± 0.82 logMAR preoperatively, and increased to 0.17 ± 0.85 logMAR, 0.19 ± 1.30 logMAR, 0.12 ± 1.15 logMAR and 0.1 ± 1.40 logMAR at 1-week, 1-, 3- and 6-month postoperative examinations, respectively. Compared to preoperative values, there was a significant improvement in UDVA after 3 and 6 months postoperatively (*p* < 0.001). Between the first postoperative week and the third and sixth postoperative month, there was a significant improvement in UDVA (*p* = 0.031 and *p* = 0.004). Between the first and third postoperative months, there was an improvement in UDVA (*p* = 0.01). All other parameters were not significant.

**Figure 9.** Distribution of uncorrected distance visual acuity.

The mean CDVA was 0.11 ± 0.85 logMAR preoperatively, 0.13 ± 0.77 logMAR, 0.12 ± 1.10 logMAR, 0.08 ± 1.05 logMAR and 0.05 ± 1.0 logMAR at 1-week, 1-, 3- and 6-month postoperative examinations, respectively. A significant increase in CDVA was observed between preoperative tests and 6 months postoperatively (*p* = 0.02). From the first postoperative week to the third postoperative month (*p* = 0.01), and to the sixth postoperative month (*p* < 0.001), there was a significant increase in CDVA. Compared to the first postoperative month, CDVA significantly increased at the third postoperative month (*p* = 0.036), and at the sixth postoperative month (*p* = 0.002). All other tested parameters to CDVA did not vary significantly with time.

CDVA was assessed in terms of safety. At 1 week postoperatively, 43% of eyes were unchanged, 43% lost 1 line of CDVA, and 7% 2 lines. At 1 month postoperatively, 64% of eyes were unchanged. While 7% of eyes gained 1 line of CDVA, 29% lost 1 line of CDVA. At 3 months postoperatively, 64% of eyes were unchanged and 36% gained 1 line of CDVA. By 6 months, 50% of eyes were unchanged, 36% gained 1 line and 7% gained 2 lines of CDVA (Figure 10).

**Figure 10.** Safety: Changes of corrected distance visual acuity in percentage.

The cumulative CDVA at 1 week postoperatively was 0.4 logMAR or worse in 7% of eyes, 0.3 logMAR or better in 93%, 0.2 logMAR or better in 86%, 0.1 logMAR or better in 29% and 0 logMAR or better in 29%. At 1 month postoperatively, CDVA was 0.2 logMAR or better in all eyes and 0.1 logMAR or better in 64%. At 3 months postoperatively, CDVA was already 0.1 logMAR or better in all eyes, and 21% had CDVA of 0 logMAR or better. At 6 months postoperatively, all eyes had a 0.1 logMAR or better and 29% had a CDVA of 0 logMAR or better (Figure 11).

The cumulative UDVA at 1 week postoperatively was 0.3 logMAR or better in all eyes, 0.2 logMAR or better in 79% of eyes, 0.1 logMAR or better in 29%, and 0 logMAR or better in 7%. One month postoperatively, UDVA was 0.2 logMAR or better in all eyes, and 0.1 logMAR or better in 14% of eyes. Three months postoperatively, UDVA was already 0.2 logMAR or better in all eyes, and 71% of eyes had a UDVA of 0.1 logMAR or better. At 6 months postoperatively, all eyes had a 0.1 logMAR or better and 14% had a UDVA of 0 logMAR or better (Figure 12).

**Figure 12.** Cumulative uncorrected distance visual acuity.

#### 3.2.3. Near Vision

The mean UNVA was 0.54 ± 1.22 logMAR preoperatively. Postoperative examinations at 1 week, then at 1, 3, and 6 months, revealed that near vision increased to 0.10 ± 0.82 logMAR, 0.09 ± 0.89 logMAR, 0.1 ± 0.77 logMAR and 0.11 ± 0.80 logMAR, respectively. Compared to the preoperative values, postoperative visual acuity increased significantly at each time point (*p* < 0.001).

The mean preoperative CNVA was 0.19 ± 0.82 logMAR. It increased to 0.08 ± 1.05 logMAR 1 week post-operatively and remained stable at each time point until at least 6 months, the last time they were tested. Postoperative CNVA values were significantly better than preoperative values (*p* = 0.02).

#### *3.3. Higher-Order Aberrations*

The RMS of higher-order aberrations (RMS-HOA) (at 6 mm diameter) increases in mean by 0.07 ± 0.1 μm from preoperatively to 6 months postoperative values (*p* = 0.04), which is significant. Customized treatment decreased the spherical aberration (Z400) decrease in mean by 0.36 ± 0.12 μm (*p* < 0.001). Quatrefoil aberrations (Z440) decreased significantly at 6 months (*p* < 0.001), compared to the preoperative values in mean, by 0.29 ± 0.11 μm (*p* < 0.001). The total coma RMS did not significantly increase in mean, changing by 0.03 ± 0.07 μm (*p* = 0.35). The total trefoil RMS did not significantly decrease, changing by 0.02 ± 0.05 μm (*p* = 0.28).

#### **4. Discussion**

In our study, postoperative UDVA and UNVA were better than preoperative values for all our patients. All patients in the study could be considered as spectacles-free for driving or for reading in standard conditions.

Most ophthalmologists consider that having a residual accommodation is an advantage for near visual acuity [16], and for some, it might be considered a necessary capacity for good outcomes. Herein, it could be demonstrated that even without any residual accommodation—all of our patients were pseudophakic—it is possible to obtain a monocular UNVA of almost 0.1 logMAR and 0.15 logMAR with PresbyLASIK in non-dominant and dominant eyes, respectively. Indeed, the target refraction values of the dominant eye (set to plano) were achieved, as confirmed by the visual acuity of 0.1 logMAR or more at 6 months postoperatively. As expected, UNVA was slightly lower, averaging 0.14 logMAR at 6 months after surgery. In the non-dominant eye (set to −0.5 D), the target refraction

value of −0.5 D was not perfectly reached; we found a slight overcorrection with a mean postoperative refraction value of −0.27 D at 6 months postoperatively. This led to a rather high uncorrected distance vision of at least 0.1 logMAR. The uncorrected near vision was 0.11 logMAR due to the slight overcorrection, which was only slightly better than in the dominant eye. Satisfaction was high among all patients, because the patients were very well informed and knew what to expect. However, it must be taken into account that the situation could be somewhat different with a larger group of patients. In any case, patient information is eminently important, especially for PresbyLASIK.

Conventional femto-PresbyLASIK is always a compromise between distance and near correction, as it creates unwanted aberrations in the pupillary region, especially spherical aberrations. If not taken into account, spherical aberrations might lead to an unsatisfactory quality of vision. With the wavefront-guided treatment, however, spherical aberrations could decrease, giving improved visual outcomes. In our study, we attempted to account for the most clinically relevant aberrations, namely, spherical aberrations (Z400). The approach allowed us to significantly decrease Z400 aberrations, even in a multifocal treatment, which usually frequently induces spherical aberrations. The Z300 (i.e., coma and trefoil) aberrations are not usually affected during multifocal treatment, as long as it is centered on the corneal apex. Therefore, we excluded patients with a kappa angle over 6◦. Wavefront-guided treatments are also apparently effective in correcting the aberration induced not only by the cornea but also by the intraocular lens [17].

Similar studies have been made recently to determine the feasibility of presbyopia correction using LASIK technologies. A recent study used an aspheric ablation profile to increase spherical aberrations and enhance near vision associated with a micromonovision [18]. However, as expected, increasing spherical aberration was associated with a decrease in far vision (UDVA of 0.08 logMAR at 6 months), with a micro-monovision that was not well tolerated in 4% of patients.

If we compare our pseudophakic population to phakic patients having undergone a wavefront-guided presbyLASIK treatment, we obtain quite similar results in terms of UDVA and UNVA. In another study, a UDVA and a UNVA of 0.22 logMAR and 0.30 log-MAR, respectively, and a 0.1 logMAR Snellen equivalent in the non-dominant eye, were achieved [19].

Compared to the treatment of presbyopia with multifocal IOLs, which is considered to be already established, wavefront-guided PresbyLASIK is a newer surgical technique, with the advantage that it is less invasive than implanting an IOL, because the treatment is applied on the eye surface. On the other hand, the application of wavefront-guided PresbyLASIK is much more demanding regarding the indication and interpretation of the objective preoperative topographic and wavefront analyses, which have a high influence on the surgical result. Wavefront-guided femto-PresbyLASIK significantly alters the biomechanical and optical properties of the cornea, which have a major influence on the surgical outcome. It is not sufficient to apply the general LASIK criteria for the indication of wavefront-guided femto-PresbyLASIK. This is probably also the reason for the not universally encouraging treatment results, because the surgical indication was made on the basis of the LASIK criteria, and the corresponding refraction and other parameters from the wavefront analysis were not taken into account. In this sense, it can be assumed that not only the suitable patients received wavefront-guided femto-PresbyLASIK treatment [11].

Our study has a few limitations. First, there is a need for an adequately sized randomized trial, since our study was a retrospective analysis with a limited number of participants. However, it must be emphasized that all patients included in this study were in a pseudophakic state, and only later requested enhancement after cataract surgery had been performed. Indeed, an alternative would have been to perform a LASIK treatment with a so-called monovision LASIK (i.e., one eye for distance and the other for near vision). In this technique, the patient selection is less crucial [20], but the non-dominant eye has a drastic decrease in far vision, and stereoscopic vision is impacted [21]. Therefore, up to 15% of patients who undergo monovision LASIK may be dissatisfied [22]. Second, we

could not compare our patient population to patients who had multifocal lens implantation. Therefore, extrapolating our results to this population of patients is not possible.

The industry and researchers should focus on more accurate or innovative wavefrontguided PresbyLASIK protocols, especially addressing the needs of pseudophakic patients, as this problem affects a large number of people in their early sixties, and could substantially improve the quality of life for these patients. Even if our results are very encouraging, there is still some room for progress. It is conceivable that an entire eye-adapted treatment protocol could be developed for each patient, based on the spherical aberration of the cornea and the IOL.

Clinicians should be aware of more precise refractive outcomes after LASIK in patients with a monofocal IOL than a multifocal IOL [23]. If the patient is not carefully selected, the surgical outcome may be worse with a multifocal IOL due to the larger optical aberrations and reduced targeting accuracy compared to LASIK. Indeed, using a laser to adapt the size of the optic and transition zone might offer a more customized treatment profile [24].

Finally, clinicians should also manage patient expectations and anxiety. In our study, UDVA fluctuated a lot during the first six months. This is a natural phenomenon caused by corneal remodeling. Initially, the multifocal treatment plan leads to light myopization, and UDVA decreases. Then the corneal epithelium compensates for the irregular corneal shape induced by laser treatment by flattening the surface, which is associated with an emmetropic shift and a slight decrease in near visual acuity. Near-vision decrease was very low, at 6 months in the dominant eye, and insignificant in the non-dominant eye.

#### **5. Conclusions**

Steepening the central cornea with wavefront-guided PresbyLASIK creates a corneal multifocality, which improved near vision in both eyes. The procedure was safe, as postoperative spherical aberration was within acceptable limits. Wavefront-guided femto-PresbyLASIK offers the possibility of treating presbyopia in pseudophakic eyes without having to perform intraocular surgery.

**Author Contributions:** B.P. developed the study design, acquired clinical data, performed statistical calculations, and substantially contributed to writing the paper. H.M. developed the methodology and contributed substantially to writing the manuscript. P.B.B. substantially contributed by advising on the paper's contents. E.E. performed substantial data curation and contributed to the study design. B.P.-E. collected the study data and advised on the paper's contents. M.R. performed data analysis and substantially contributed the study design. Z.C. contributed substantially to the methodology and statistical calculations and substantially contributed to writing the paper. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Eye Center Vidar Orasis Swiss (protocol code 2018-34).

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** The data presented in this study are available on request from the authors; the datasets, in particular, are archived in the clinics treated. The data are not publicly available as they contain information that could compromise the privacy of the participants.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

