One-stage versus two-stage bilateral implantable collamer lens implantation: a comparison of efficacy and safety.

Implantable collamer lens implantation (ICL) represents a safe and effective treatment for myopia and myopic astigmatism. To compare the outcomes of a bilateral one-stage same day approach to a two-stage approach, the databases of the University Eye Hospital Munich, Ludwig Maximilians-University and Smile Eyes Linz, Austria were screened for eyes that had undergone ICL implantation. Two-stage surgery was performed at an interval of 1 day (17 patients), 2 days (19 patients) and 1 week (2 patients). Variables analyzed were preoperative, 1-day and last follow-up uncorrected distance (UDVA) and corrected distance visual acuity (CDVA), manifest refraction, refractive spherical equivalent (SEQ), astigmatism, age, endothelial cell count (ECD), intraocular pressure (IOP) and ICL vaulting. In total, 178 eyes (100 eyes one-stage, 78 eyes two-stage) of 89 patients were included in this study. Mean follow-up was 1.1 ± 0.8 and 1.3 ± 0.5 years. Mean preoperative SEQ was - 7.9 ± 2.6 diopters (D) in the one-stage and - 8.0 ± 1.7 D in the two-stage group (p = 0.63) and improved to 0.00 ± 0.40 and - 0.20 ± 0.40 D at end of follow-up, showing slightly better stability in the one-stage group (p = 0.004). There was no difference in the efficacy (1.1 vs. 1.2, p = 0.06) and the safety index (1.2 vs. 1.2, p = 0.60) between the two groups. No eye (0%) in either group lost 2 lines or more of UDVA (p > 0.99). Refraction within ± 0.50 D and ± 1.00 D around target was achieved comparably often (89 vs. 86%, p = 0.65; 99 vs. 99%, p > 0.99). Endothelial cell loss was slightly higher in the two-stage group (1.3 vs. 4.3%). Vaulting at the final follow up was higher in the one-stage group (373.8 ± 205.4 µm vs. 260.3 ± 153.5 µm, p = 0.00007). There were no serious intraoperative complications in either group. In conclusion, this study demonstrates that both the one- and two-stage approaches are equally effective, predictable and safe. Regarding endothelial cell loss, vaulting and SEQ stability, the one-stage group showed slightly better outcomes, but these results are clinically questionable because they are so small. Larger studies are needed to quantitatively evaluate a potential benefit.

Optimizing Refractive Outcomes of SMILE: Artificial Intelligence versus Conventional State-of-the-Art Nomograms.

PURPOSE: AI (artificial intelligence)-based methodologies have become established tools for researchers and physicians in the entire field of ophthalmology. However, the potential of AI to optimize the refractive outcome of keratorefractive surgery by means of machine learning (ML)-based nomograms has not been exhausted yet. In this study, we wanted to comprehensively compare state-of-the-art conventional nomograms for Small-Incision-Lenticule-Extraction (SMILE) with a novel ML-based nomogram regarding both their spherical and astigmatic predictability. METHODS: A total of 1,342 eyes were analyzed for creation of three different nomograms based on a linear model (LM), a generalized additive mixed model (GAMM) and an artificial-neuronal-network (ANN), respectively. A total of 16 patient- and treatment-related features were included. Each model was trained by 895 eyes and validated by the remaining 447 eyes. Predictability was assessed by the difference between attempted and achieved change in spherical equivalent (SE) and the difference between target induced astigmatism (TIA) and surgically induced astigmatism (SIA). The root mean squared error (RMSE) of each model was computed as a measure of overall model performance. RESULTS: The RMSE of LM, GAMM and ANN were 0.355, 0.348 and 0.367 for the prediction of SE and 0.279, 0.278 and 0.290 for the astigmatic correction, respectively. By applying the created models, the theoretical yield of eyes within ±0.50 D of SE from target refraction improved from 82 to 83% (LM), 84% (GAMM) and 83% (ANN), respectively. Astigmatic outcomes showed an improvement of eyes within ±0.50 D from TIA from 90 to 93% (LM), 93% (GAMM) and 92% (ANN), respectively. Subjective manifest refraction was the single most influential covariate in all models. CONCLUSION: Machine learning endorsed the validity of state-of-the-art linear and non-linear SMILE nomograms. However, improving the accuracy of subjective manifest refraction seems warranted for optimizing ±0.50 D SE predictability beyond an apparent methodological 90% limit.

Comparison of Visual and Refractive Outcome between Two Methods of Corneal Marking for Toric Implantable Collamer Lenses (TICL) in Phakic Eyes.

PURPOSE: To compare the efficacy of digital-assisted reference marking for toric implantable collamer lenses (Callisto Eye System) with manual marking technique using a slit lamp markeur. METHODS: This study included patients that underwent implantation of a toric implantable collamer lens (EVO Visian toric ICL, Staar Surgical). Patients were included if they had a myopia above -3 diopters (D) and regular corneal astigmatism of 0.75 diopters or higher. Between both groups a 1:2 matching regarding similar preoperative level of myopia and astigmatism was performed. Visual and refractive outcomes were evaluated. Vector analysis was performed to evaluate total astigmatic changes. RESULTS: This study comprised 57 eyes of 57 patients with 19 eyes in the digital group and 38 eyes in the manual marking group. Postoperatively there were no statistically significant differences between both groups in UDVA (p = 0.467), spherical equivalent (SE) (p = 0.864), sphere (p = 0.761) and cylinder (p = 0.878). Vector analysis showed a slightly more accurate postoperative refractive astigmatism in the manual group (0.26 D at 107° ± 0.50 D) compared to the digital marking group (0.31 D at 107° ± 0.45 D), nevertheless with no statistically significant differences between both groups. CONCLUSIONS: A digital tracking approach for toric ICL alignment was an efficient and safe method for toric marking with similar results regarding visual and refractive outcomes compared to a conventional corneal marking method. Nevertheless, image-guided surgery helped to streamline the workflow in refractive ICL surgery.

IOL Power Calculations and Cataract Surgery in Eyes with Previous Small Incision Lenticule Extraction.

Small incision lenticule extraction (SMILE), with over 5 million procedures globally performed, will challenge ophthalmologists in the foreseeable future with accurate intraocular lens power calculations in an ageing population. After more than one decade since the introduction of SMILE, only one case report of cataract surgery with IOL implantation after SMILE is present in the peer-reviewed literature. Hence, the scope of the present multicenter study was to compare the IOL power calculation accuracy in post-SMILE eyes between ray tracing and a range of empirically optimized formulae available in the ASCRS post-keratorefractive surgery IOL power online calculator. In our study of 11 post-SMILE eyes undergoing cataract surgery, ray tracing showed the smallest mean absolute error (0.40 D) and yielded the largest percentage of eyes within ±0.50/±1.00 D (82/91%). The next best conventional formula was the Potvin-Hill formula with a mean absolute error of 0.66 D and an ±0.50/±1.00 D accuracy of 45 and 73%, respectively. Analyzing this first cohort of post-SMILE eyes undergoing cataract surgery and IOL implantation, ray tracing showed superior predictability in IOL power calculation over empirically optimized IOL power calculation formulae that were originally intended for use after Excimer-based keratorefractive procedures.

Corneal Collagen Crosslinking (CXL) for Corneal Ectasia after Small Incision Lenticule Extraction (SMILE). / Korneales Kollagen-Crosslinking (CXL) bei Hornhautektasie nach SMILE (Small Incision Lenticule Extraction).

With an estimated incidence of 0.011%, the SMILE procedure seems to have the lowest risk of postoperative keratectasia among contemporary keratorefractive procedures. Nevertheless, due to the novelty of the procedure as well as the lack of data, no clear superiority over femto-LASIK or PRK can be stated at this time. In this respect, application of the identical tomographic screening criteria previously developed for excimer-based procedures is of paramount importance to minimize the risk of corneal ectasia. As an adjunct to conventional corneal tomography, newer imaging modalities such as OCT-based epithelial mapping should be used for preoperative screening before keratorefractive surgery. Corneal crosslinking is an established treatment modality for post-SMILE keratectasia, which promises high success rates especially in early stages. The present case report illustrates these diagnostic and therapeutic considerations.

Determinants of Subjective Quality of Vision After Phakic Intraocular Lens Implantation.

PURPOSE: To evaluate postoperative subjective quality of vision in patients who underwent Implantable Collamer Lens (ICL) (STAAR Surgical) implantation for correction of myopia and to identify potential predictive parameters. METHODS: In this single-center cross-sectional study, a total of 162 eyes of 81 patients (58 women, 23 men) who underwent ICL implantation were analyzed. The Quality of Vision (QOV) questionnaire was used to assess patient-reported outcomes. Baseline characteristics (eg, age), treatment parameters (eg, surgical corrected refraction), and refractive (eg, residual refraction) and visual (eg, uncorrected distance visual acuity) outcomes were analyzed regarding their effect on QOV. RESULTS: Mean age was 33.3 ± 7.0 years (range: 21 to 51 years) and mean preoperative spherical equivalent was -8.42 ± 2.49 diopters (D) (range: -3.25 to -14.38 D). After a mean postoperative follow-up period of 19 ± 14 months (range: 6 to 54 months), the safety index score was 1.23 ± 0.21 and the efficacy index score was 1.17 ± 0.22. The mean QOV scores were 35.5 ± 11.3, 32.2 ± 11.1, and 23.3 ± 16.1 for frequency, severity, and bothersomeness, respectively. The most frequently experienced symptoms were halos (90.1%) and glare (66.7%). Halos appeared in 66.7% of the patients "occasionally" and 5 of them (6.2%) experienced them "very often." Only 1 patient (1.2%) classified halos as "very bothersome." Patients older than 36 years reported visual symptoms more frequently (P < .05) and showed higher bothersomeness scores (P = .01). CONCLUSIONS: Halos are the most commonly perceived long-term visual disturbance after myopic ICL implantation with a central hole. Visual symptoms can persist more than 6 months postoperatively, causing only minor disturbances in most cases. Older patients seem more prone to experiencing these symptoms. [J Refract Surg. 2022;38(5):280-287.].

Femtosecond laser-assisted descemetorhexis for Descemet membrane endothelial keratoplasty: cell-based and tissue-based ex vivo analysis of precision and safety.

PURPOSE: To analyze precision and safety of femtosecond laser-assisted descemetorhexis and postoperative corneal wound healing in human ex vivo specimens. SETTING: Department of Ophthalmology, University Hospital, LMU Munich, Munich, Germany. DESIGN: Experimental ex vivo study. METHODS: 4 donor corneas underwent femtosecond laser-assisted descemetorhexis. The descemetorhexis was performed using the LDV Z8 femtosecond laser, followed by live/dead staining, phase contrast microscopy, and scanning electron microscopy. The descemetorhexis parameters were set using a modified optical coherence tomography image capturing of 8 segments within a focus of 100 µm at the posterior corneal stroma (reversed capsulotomy program). RESULTS: Live/dead sample staining analysis demonstrated that the femtosecond laser had minimal impact on the vitality of surrounding endothelial cells. Phase contrast microscopy and scanning electron microscopy evaluation showed that the laser produced precise, clear-cut edges, leaving no stromal tissue bridges. CONCLUSIONS: Femtosecond laser-assisted descemetorhexis could serve as a safe and precise technique with only minimal endothelial cell damage. To minimize stromal damage, further laser energy profile adjustments are necessary to optimize corneal treatment within different stages of corneal tissue swelling.

Impact of extreme (flat and steep) keratometry on the safety and efficacy of small incision lenticule extraction (SMILE).

Little is known about the connection between preoperative keratometry and postoperative results of myopic small-incision lenticule extraction (SMILE). To determine the influence of extreme (flat and steep) corneal keratometry on the safety and efficacy of SMILE, the databases of the Department of Ophthalmology, Ludwig-Maximilians-University Munich, Germany, and SMILE Eyes Linz, Austria, were screened for patients with steep and flat keratometry who had undergone SMILE. In this cross-sectional matched comparative cohort study, eyes with markedly flat (< 42.0 diopters; D) or steep (≥ 47.0D) preoperative corneal keratometry were matched to a cohort of eyes with regular keratometry (42.0-46.9D) by preoperative manifest refractive spherical equivalent and cylinder, age, corrected distance visual acuity and surgical SMILE parameters. The standardized graphs and terms for refractive surgery results were applied to compare the three groups. Changes in higher order aberrations (HOAs) were evaluated on Scheimpflug imaging. In total, 63 eyes (21 each) of 54 patients with a mean refractive spherical equivalent of - 5.21 ± 1.59 D were followed up for a mean of 9.2 ± 6.1 (minimum ≥ 3) months. Mean baseline keratometry was 41.3 ± 0.7D (flat), 45.5 ± 1.0D (regular) and 47.7 ± 0.6D (steep) (p < 0.0001). Compared to the regular group, the flat and the steep cornea group resulted in a non-inferior percentage of eyes within ± 0.50 D of target refraction (p = 0.20), uncorrected distance visual acuity (p = 0.95) and corrected distance visual acuity (p = 0.20). Flat corneas however experienced a stronger induction of spherical aberration (SA) compared to the steep group (p = 0.0005). In conclusion, non-inferior outcomes of SMILE can also be expected in eyes with steep (≥ 47D) or flat (< 42D) preoperative keratometry, while SMILE however induces more SA in eyes with a flat keratometry.

Corneal optical density in Fuchs endothelial dystrophy determined by anterior segment optical coherence tomography.

PURPOSE: In this study, we propose a method to grade corneal stromal opacity using optical density measurements by anterior segment optical coherence tomography (AS-OCT) and validate the approach in Fuchs endothelial corneal dystrophy (FECD). METHODS: A retrospective analysis of human corneal OCT scans was performed on 48 eyes of 32 patients with FECD and 33 control eyes of 21 patients using the Carl Zeiss Cirrus HD-OCT 5000. In addition, corneal edema in fresh rabbit cadaver eyes was artificially induced by distilled water and imaged with the Thorlabs TELESTO-II spectral domain OCT at different time points during saturation. The increase of opacity due to corneal edema was proposed to directly correlate with enhanced reflectivity sites in the OCT images, corresponding to higher optical density. The increase was determined as the image area above a statistically established gray-scale value using ImageJ and correlated with other disease characteristics. RESULTS: Optical densities in human corneas showed significant differences between FECD patients and the control group (p = 0.002). The increased optical densities determined in FECD corneas correlated well with other disease characteristics such as corneal pachymetry or visual acuity. Likewise, rabbit corneas showed a time dependent increase in thickness and in corneal optical density during soaking in distilled water. CONCLUSION: This study presents corneal optical density by AS-OCT as an objective value for corneal changes in FECD. Complementing other diagnostic tools in FECD the assessment of corneal optical density may identify progression of FECD, gauge novel therapeutic strategies and support risk and benefit analyses for corneal surgery.

[SMILE - Small Incision Lenticule Extraction]. / SMILE ­ Small Incision Lenticule Extraction.

Refractive lenticule extraction is a corneal surgical technique that uses a femtosecond laser exclusively to create an intrastromal refractive lenticule for the correction of myopia and myopic astigmatism. In small incision lenticule extraction (SMILE) the generated refractive lenticule is subsequently extracted through a small incision. The reported efficacy, predictability and safety of the flap-less SMILE procedure is similar to those of femtosecond laser in situ keratomileusis (LASIK). Advantages of SMILE over LASIK include less iatrogenic dry eye, fewer induced higher-order aberrations, and potentially less biomechanical weakening of the cornea. However, there is a steeper surgeon learning curve for SMILE as the procedure is technically more challenging than LASIK. Furthermore, the current SMILE laser platform cannot use cyclotorsion control or eye-tracking technology and retreatment options are more complex compared to LASIK. This review looks at patient selection, surgical method, possible complications, retreatment options, and postoperative outcome of the SMILE technique.

Penetrating keratoplasty after complicated small incision lenticule extraction a case report.

PURPOSE: We present an interesting case of a 26-year-old woman who underwent penetrating keratoplasty due to complete corneal scarring on the right eye after complicated myopic SMILE. OBSERVATIONS: The spherical equivalent before laser treatment was -4.38D on the right eye and -4.00D on the left eye and topography showed a with-the-rule astigmatism on both eyes. The documented laser procedure was uneventful but wrong separation of the lenticule made a complete extraction of the lenticule not possible. The postoperative spherical equivalent showed -4,125D with an irregular astigmatism due to corneal scarring throughout the complete corneal stroma documented in OCT measurements. Due to serious anatomical changes of the cornea an uneventful penetrating keratoplasty was performed. CONCLUSION AND IMPORTANCE: SMILE procedure should be carefully performed as especially the lenticule separation and extraction can be a surgical challenge. In doubt, separation of the lenticule should not be enforced as it may lead to devastating outcome as presented in this case.

Intraocular Lens Power Calculation after Small Incision Lenticule Extraction.

With more than 1.5 million Small Incision Lenticule Extraction (SMILE) procedures having already been performed worldwide in an ageing population, intraocular lens (IOL) power calculation in post-SMILE eyes will inevitably become a common challenge for ophthalmologists. Since no refractive outcomes of cataract surgery following SMILE have been published, there is a lack of empirical data for optimizing IOL power calculation. Using the ray tracing as the standard of reference - a purely physical method that obviates the need for any empirical optimization - we analyzed the agreement of various IOL power calculation formulas derived from the American Society of Cataract and Refractive Surgeons (ASCRS) post-keratorefractive surgery online calculator. In our study of 88 post-SMILE eyes, the Masket formula showed the smallest mean prediction error [-0.36 ± 0.32 diopters (D)] and median absolute error (0.33D) and yielded the largest percentage of eyes within ±0.50D (70%) in reference to ray tracing. Non-inferior refractive prediction errors and ±0.50D accuracies were achieved by the Barrett True K, Barrett True K No History and the Potvin-Hill formula. Use of these formulas in conjunction with ray tracing is recommended until sufficient data for empirical optimization of IOL power calculation after SMILE is available.

Corneal wavefront aberrations and subjective quality of vision after small incision lenticule extraction.

PURPOSE: To analyse in depth the associations between objectively measured corneal higher-order aberrations (HOAs) and subjectively perceived visual quality after small incision lenticule extraction (SMILE) as quantified with the standardized and clinically validated quality of vision (QOV) questionnaire. METHODS: This cross-sectional study included patients after bilateral simultaneous SMILE for the treatment of myopia and/or myopic astigmatism with plano target refraction. Scheimpflug imaging (Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany) was used to objectively quantify corneal HOAs. The standardized and validated QOV questionnaire was employed to gauge patients' subjectively perceived visual quality regarding frequency, severity and bothering effect of visual disturbances. RESULTS: A total of 394 eyes of 197 patients with a mean age of 32.4 ± 7.7 years and a mean postoperative follow-up of 24.3 ± 14.1 months were included. SMILE induced a statistically significant (p < 0.001) increase in spherical aberration (0.074 ± 0.131 µm), coma (0.142 ± 0.179 µm), trefoil (0.018 ± 0.067 µm) as well as in total HOAs (0.191 ± 0.176 µm). Surgically induced and postoperative levels of HOA showed no correlation with the three QOV scores representative of overall visual symptom frequency, severity and bothering effect (all R2 values ≤ 0.016). In addition, the associations between specific visual symptoms (e.g. starburst) and singular HOA terms (e.g. haloes) were very weak (all Rho values ≤ 0.164). CONCLUSIONS: Small incision lenticule extraction induced significant amounts of corneal HOAs that, however, showed no clear relationships to patient-reported QOV or specific long-term visual symptoms.

SMILE Versus Implantable Collamer Lens Implantation for High Myopia: A Matched Comparative Study.

PURPOSE: To compare the safety, efficacy, and patient-reported quality of vision of small incision lenticule extraction (SMILE) and implantable Collamer lens (ICL) implantation for the treatment of high myopia. METHODS: A database of 1,634 SMILE (Carl Zeiss Meditec AG, Jena, Germany) and 225 ICL implantation (STAAR Surgical, Monrovia, CA) procedures was screened for patients with a binocular preoperative manifest refraction spherical equivalent between -6.00 and -10.00 diopters (D) and plano target refraction. One-to-one matching was performed by preoperative manifest refraction spherical equivalent, age, and pupil size. All identified patients were then prospectively examined at their next regular postoperative follow-up visit and presented with the standardized and clinically validated Quality of Vision questionnaire to gauge patient-reported postoperative visual quality. RESULTS: A total of 80 eyes (40 patients) were eligible for 1:1 matching. Mean postoperative follow-up was 27.8 ± 14.3 months in the SMILE group and 26.6 ± 17.7 months in the ICL group (P = .44). Regarding the percentage of eyes within ±0.50 D of plano target, refractive predictability was better in eyes treated with ICL implantation (90%) than SMILE (72.5%) (P = .045). Mean UDVA was comparable (ICL: -0.09 ± 0.10 logMAR; SMILE: -0.06 ± 0.09 logMAR; P < .09), but the efficacy (1.28 vs 1.05; P < .001) and safety (1.31 ± 0.22 vs 1.10 ± 0.25; P < .001) indices were higher after ICL implantation. ICL implantation induced significantly fewer higher order aberrations (total higher order aberrations: SMILE 0.724 ± 0.174 µm vs ICL 0.436 ± 0.114 µm; P < .01). Regarding subjective quality of vision, patients who had ICL implantation were significantly less bothered by visual disturbances, which were mainly halos after ICL and starbursts and fluctuations of vision after SMILE (P < .05). CONCLUSIONS: In this refraction-matched comparative study, ICL implantation for high myopia yielded better refractive accuracy, better uncorrected distance visual acuity, fewer higher order aberrations, and better subjective quality of vision than SMILE. [J Refract Surg. 2020;36(3):150-159.].

Ex vivo excimer laser ablation of cornea guttata and ROCK inhibitor-aided endothelial recolonization of ablated central cornea.

PURPOSE: To determine whether excimer laser ablation of guttae is a viable strategy for removal of diseased tissue in Fuchs' endothelial corneal dystrophy (FECD) on excised human Descemet membranes and whether an excimer laser-created wound on healthy human corneas ex vivo is recolonized with corneal endothelial cells. METHODS: Descemet membranes of FECD patients and corneal endothelium of normal human corneas were ablated ex vivo using an excimer laser licensed for glaucoma surgery. Specimens were kept in cell culture medium supplemented with 10 µm of rho-kinase inhibitor ripasudil. Corneal endothelial cell regeneration was observed using light and electron scanning microscopy. Furthermore, the whole corneal samples were evaluated by haematoxylin/eosin staining and immunohistochemical analysis using antibodies against Na+ /K+ -ATPase. RESULTS: Guttae and corneal endothelium could be ablated with an excimer laser without total ultrastructural damage to the Descemet membrane or stroma. Nearly complete endothelial wound closure was accomplished after 26-38 days in treated corneas. Light and electron scanning microscopy suggested the establishment of a layer of flat endothelial cells. Additionally, Na+ /K+ -ATPase expression could only be observed on the inner side of the Descemet membrane. CONCLUSION: Our proof of concept study demonstrated that excimer lasers can be used to ablate diseased tissue from excised FECD Descemet membranes ex vivo. Additionally, corneal endothelial cells recolonize a previously ablated endothelial area in healthy human corneas ex vivo under treatment with ripasudil. Thus, our results are the first experimental basis to further investigate the feasibility of an excimer laser ablation as a graftless FECD treatment option.

Peroxiredoxin-1 regulates lipid peroxidation in corneal endothelial cells.

Corneal transparency is maintained by a monolayer of corneal endothelial cells. Defects in corneal endothelial cells (CEnCs) can be rectified surgically through transplantation. Fuchs' endothelial corneal dystrophy (FECD) is the foremost cause of endothelial dysfunction and the leading indication for transplantation. Increased sensitivity of CEnCs to oxidative stress is thought to contribute to the pathogenesis of FECD through increased apoptosis. In part, this is thought to be due to loss of NRF2 expression: a global regulator of oxidative stress. We demonstrate that expression of the redox sensor, peroxiredoxin 1 (PRDX1) is selectively lost from CEnCs in FECD patient samples. We reveal that expression of PRDX1 is necessary to control the response of CEnCs to agents that cause lipid peroxidation. Iron-dependent lipid peroxidation drives non-apoptotic cell death termed ferroptosis. We establish that the inhibitor of ferroptosis, ferrostatin-1 rescues lipid peroxidation and cell death in CEnCs. Furthermore, we provide evidence that the transcription factor NRF2 similarly regulates lipid peroxidation in CEnCs.