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Bojan Pajic,1–4 Iraklis Vastardis,1 Predrag Rajkovic,5 Brigitte Pajic-Eggspuehler,1 Daniel M Aebersold,6 Zeljka Cvejic2 1Eye Clinic ORASIS, Swiss Eye Research Foundation, Reinach AG, Switzerland; 2Department of Physics, Faculty of Sciences, University of Novi Sad, Novi Sad,3Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia; 4Division of Ophthalmology, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland; 5Department of Mathematics, Faculty of Mechanical Engineering, University of Niš, Niš, Serbia; 6Department of Radiation Oncology, Inselspital, Bern University Hospital, Bern, Switzerland Purpose: Pterygium is a common lesion affecting the population in countries with high levels of ultraviolet exposure. The final shape of a pterygium is the result of a growth pattern, which remains poorly understood. This manuscript provides a mathematical analysis as a tool to determine the shape of human pterygia.Materials and methods: Eighteen patients, all affected by nasal unilateral pterygia, were randomly selected from our patient database independently of sex, origin, or race. We included all primary or recurrent pterygia with signs of proliferation, dry eye, and induction of astigmatism. Pseudopterygia were excluded from this study. Pterygia were outlined and analyzed mathematically using a Cartesian coordinate system with two axes (X, Y) and five accurate landmarks of the pterygium.Results: In 13 patients (72%), the shape of the pterygia was hyperbolic and in five patients (28%), the shape was rather elliptical.Conclusion: This analysis gives a highly accurate mathematical description of the shape of human pterygia. This might help to better assess the clinical results and outcome of the great variety of therapeutic approaches concerning these lesions. Keywords: etiology, pterygium, limbal stem cells, stem cells dysfunction, mathematical shape analysis

Iraklis Vastardis,1 Brigitte Pajic-Eggspühler,1 Jörg Müller,1,2 Zeljka Cvejic,2 Bojan Pajic,1–4 1Swiss Eye Research Foundation, Orasis Eye Clinic, Aargau, Reinach, Switzerland; 2Faculty of Physics, University of Novi Sad, Novi Sad, Serbia; 3Department of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland; 4Medical Faculty, Military Medical Academy, University of Defence, Belgrade, Serbia Purpose: To report the visual outcomes of the femtosecond laser-assisted multifocal aspheric corneal ablation profile using a mini-monovision approach and to evaluate if corneal multifocality was effective, and to report the relative benefits of this approach.Patients and methods: Bilateral femtosecond laser-assisted in situ keratomileusis using a multifocal aspheric corneal ablation profile was performed on 19 hyperopic patients (38 eyes). They were divided into two groups based on eye dominance: dominant eye (DE) group targeting emmetropia and the nondominant eye (NDE) group targeting -0.5 D slight myopia. The uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), and retreatment rates were reported from baseline to 6 months.Results: The UNVA, UIVA, and UDVA improved significantly in both groups (Kruskal–Wallis test, DE and NDE: P

Mirko Resan,1,2 Miroslav Vukosavljevic,1,2 Danilo Vojvodic,2,3 Brigitte Pajic-Eggspuehler,4 Bojan Pajic2,4–6 1Eye Clinic, Military Medical Academy, Belgrade, Serbia; 2Faculty of Medicine of the Military Medical Academy, University of Defense, Belgrade, Serbia; 3Department for Clinical and Experimental Immunology, Institute for Medical Research, Military Medical Academy, Belgrade, Serbia; 4Eye Clinic ORASIS, Swiss Eye Research Foundation, Reinach AG, Switzerland; 5Department of Physics, Faculty of Science, University of Novi Sad, Novi Sad, Serbia; 6Division of Ophthalmology, Department of Clinical Neurosciences, University Hospitals of Geneva, Switzerland Purpose: To evaluate the participation of proinflammatory cytokines in the acute phase of corneal wound-healing response after excimer laser treatment. Methods: The study included 68 myopic eyes up to -3.0 diopters divided into two groups: 1) eyes treated with laser in situ keratomileusis (LASIK) (n=31) and 2) eyes treated with photorefractive keratectomy (PRK) (n=37). Each group was then divided into three subgroups based on tear sampling times: before (0 hours), 1 hour after, and 24 hours after treatment. The tear fluid was sampled from lower lateral tear meniscus using a cellulose microsurgical sponge. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 in tear fluid were determined by flow cytometry method. Results: Statistical significance was observed in the concentrations of TNF-α (P=0.0421) and IL-1β (P=0.0225) between samples collected 1 and 24 hours after PRK treatment in favor of samples collected 1 hour after treatment. IL-6 concentration changes showed a significant increase in the PRK group in both time intervals following treatment compared to pretreatment (0 hour/1 hour, P=0.0031; 0 hour/24 hours, P=0.0059). For IL-8 concentrations, significant differences were observed between control and experimental groups in samples collected 1 hour after LASIK and 1 hour after PRK treatment (P

Bojan Pajic,1–3 Iraklis Vastardis,1,2 Zisis Gatzioufas,1 Brigitte Pajic-Eggspuehler1 1Swiss Eye Research Foundation, Eye Clinic ORASIS, Reinach, Switzerland; 2Eye Hospital VIDAR-ORASIS Swiss, Department of Physics, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia; 3Medical Faculty, Military Medical Academy, University of Defense, Belgrade, Serbia Background: The purpose of this work is to report our experience using the new Z8 laser system for femtosecond laser-assisted cataract surgery (FLACS) and to provide a sample of the performance and safety results using this new technology. Methods: This prospective observational study was performed at the Swiss Eye Research Foundation, Eye Clinic ORASIS, Reinach, Switzerland. Fourteen patients were subjected to unilateral FLACS. Capsulotomy and lens fragmentation were performed with the aid of the LDV Z8 femtosecond laser system. Ease of phacoemulsification (on a 4-point scale), completeness of capsulotomy (on a 10-point scale), time for preparation of femtosecond laser (minutes), effective phacoemulsification time (seconds), total duration of surgery (minutes), and safety of the procedure were evaluated. Results: Ease of fragmentation and completeness of capsulotomy were estimated at 3.9 and 9.9, respectively. The preparation time for femtosecond was 3.6±0.7 minutes, effective phacoemulsification time was 2.5±3.1 seconds, and total duration of the FLACS procedure was 16.3±4.5 minutes. No major complications were observed. Approximately 42% of all patients (6/14) showed Descemet’s folds directly postoperatively. Conclusion: FLACS with the LDV Z8 system was characterized by complete capsulotomy and highly effective and reproducible lens fragmentation. The safety of the procedure was very good as perceived by the surgeon operating in this observational case series. The cost to benefit ratio should be further debated by assessing the results of a major prospective study, which is required for valid evaluation of the efficiency and safety of the LDV Z8 laser system and of FLACS in general. Keywords: femtosecond laser, cataract surgery, effective phacoemulsification time, complications

Bojan Pajic,1–3,5 Iraklis Vastardis,1,3 Brigitte Pajic-Eggspuehler,1 Zisis Gatzioufas,2 Farhad Hafezi2,4 1Swiss Eye Research Foundation, Eye Clinic ORASIS, Reinach, Switzerland; 2Division of Ophthalmology, Department of Clinical Neurosciences, University Hospital of Geneva, Geneva, Switzerland; 3Eye Hospital VIDAR-ORASIS Swiss, University of Novi Sad, Faculty of Physics, Novi Sad, Serbia; 4Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 5Military Medical Academy, University of Defense, Belgrade, SerbiaPurpose: To compare a femtosecond laser with a microkeratome for flap creation during laser in situ keratomileusis (LASIK) in terms of flap thickness predictability and visual outcomes.Patients and methods: This was a prospective, randomized, masked, paired-eye study. Forty-four patients (34 females) who received bilateral LASIK were included. Patients were stratified by ocular dominance, and they then underwent randomization of flap creation using the femtosecond laser on one eye and undergoing the microkeratome procedure on the other one. The visual outcome differences between the corrected distance visual acuity (CDVA) at baseline and the uncorrected distance visual acuity (UDVA) on the first day postoperatively were set as the efficiency index for both groups. All visual acuity outcome results and the deviation of flap thickness were evaluated. P-values

Background/Aim. Corneal cross-linking (CXL) treatment shows the best results in stabilizing the cornea and stopping the progress of the ectatic process. The aim of the study was to assess the impact of CXL on the keratoconus regarding higher-order aberrations (HOAs) and potential improvement of visual function. Methods. In 19 patients, a standard epithelium-off CXL was performed with an energy density of three mW/cm2 for half an hour. The cornea was examined by Pentacam topography before CXL and one and six months after CXL. Best-corrected visual acuity (BCVA), topographic data, and aberrations were collected. Results. A significant reduction in vertical coma was observed from preoperative -1.03 ± 1.89 to -0.74 ± 1.73 (p = 0.004) six months after CXL, and in spherical aberration from preoperative -0.22 ± 1.05 to -0.08 ± 1.13 (p = 0.002) six months after CXL. Root mean square (RMS) HOAs six months after CXL also significantly reduced from 2.31 ± 1.82 to 2.26 ± 1.84 six months after CXL (p = 0.001). BCVA improved from preoperative 0.43 ± 0.15 to 0.71 ± 0.19 six months after surgery (p < 0.001). Conclusion. CXL is a very potent treatment method for keratoconus, which significantly reduces certain corneal wavefront aberrations, especially vertical coma, spherical aberration, and RMS, and leads to a significant improvement in visual acuity.

Background/Aim. Immune response and consequent inflammatory process which originate on ocular surface after a trauma are mediated by cytokines. Photoablation of corneal stroma performed by excimer laser causes surgically induced trauma. Interleukin-6 (IL-6) is mostly known as a proinflammatory cytokine. However, it also has regenerative and anti-inflammatory effects. It is supposed that this cytokine is likely to play a significant role in the process of corneal wound healing response after photoablation of stroma carried out by laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) methods. The aim of this study was to determine and compare the levels of IL-6 in tears before and after treatment with LASIK and PRK methods. Methods. The study included 68 shortsighted eyes up to -3.0 diopter sphere, i.e. 198 samples of tears (per three samples taken from each of the eyes), divided into two groups according to the kind of excimer laser intervention performed: the group 1 - eyes treated by LASIK method (n = 31), and the group 2 - eyes treated by the PRK method (n = 37). The samples of tears were taken from each eye at the following time points: before excimer laser treatment (0 h, the control group), 1 h after the treatment (1 h) and 24 h after the treatment (24 h). The patients did not use anti-inflammatory therapy 24 h after the intervention. Tear samples were collected using microsurgical sponge. Level of IL-6 in tear fluid was determined by the flow cytometry method, applying a commercial test kit which allowed cytokine detection from a small sample volume. Results. The values of IL-6 were detectable in 16% of samples before LASIK treatment and in 30% of samples before PRK treatment. One h after the treatment IL-6 was detectable in 29% of samples for the LASIK group and 43% of samples for the PRK group, and 24 h after the treatment it was detectable in 19% of samples for the LASIK group and in 57% of samples for the PRK group. When we analyzed the dynamics of IL-6 production in particular groups, we noticed that both in the LASIK and PRK group the number of samples with increased values of IL-6 after 1 h, and after 24 h, was considerably larger than the number of samples with decreased values of IL-6 after the intervention. Analyzing the dynamics of IL-6 concentration changes in the 1 h samples vs 24 h samples there was a statistically significant increase in the number of samples with IL-6 concentration decline in the LASIK group, while at the same time no considerable changes occurred in the PRK group. Comparing average IL-6 values between the two treatment groups in all tear samples at 0 h, 1 h and 24 h after intervention a significantly higher level in the PRK group 24 h after procedure (p = 0.0031) was detected. Conclusion. IL-6 level in tears increases 1 h and 24 h after LASIK and PRK treatments. This increment is significantly larger 24 h after the treatment with the PRK method than with the LASIK method. Changes of IL-6 production levels in tears after excimer laser treatment indicate that this cytokine takes part in the corneal recovery process after stromal photoablation.

Background and Objectives : The purpose of this study was to compare two commercially available specular microscopes (Tomey EM-4000 and Nidek CEM-530) in a real-life clinical setting in terms of intra- and interdevice variability. The study was conducted on all patients seen in a clinical practice specializing in anterior segment pathologies, regardless of the purpose of their visit. Materials and Methods : In total, 112 eyes of 56 patients (age 23-85 years old) were included in the study. Each eye was measured three times with each device (for a total of six measurements), and results for central corneal thickness (CCT) and corneal endothelial cell density (ECD) were recorded. The results were then evaluated with the D'Agostino-Pearson normality test and compared with a Wilcoxon signed-rank test, t -test, ANOVA or Mann-Whitney test for intra- and interdevice variability. Results : Both specular microscopes produced very reliable reproducible intradevice results: The Tomey EM-4000 measured an ECD of 2390 ± 49.57 cells/mm 2 (mean ± standard error of mean); the range was 799-3010 cells/mm 2 . The determined CCT was 546 ± 5.104 µm (mean ± standard error of mean [SEM]); the range was 425-615 µm. The measurements with the Nidek CEM-530 revealed an ECD of 2417 ± 0.09 cells/mm 2 (mean ± SEM); the range was 505-3461 cells/mm 2 (mean ± SEM). The mean CCT detected was 546.3 ± 4.937 µm (mean ± SEM); the range was 431-621 µm. The interdevice differences were statistically significant for both parameters, ECD ( p = 0.0175) and CCT ( p = 0.0125) ( p < 0.05). Conclusions : The Nidek CEM-530 and the Tomey EM-4000 both produced reliable and reproducible results in terms of ECD and CCT. The absolute measurements were statistically significantly different for CCT and ECD for both devices; the Nidek produces slightly higher values.

Background and Objectives : Early diagnosis of the exudative form of age-related macular degeneration (AMD) is very important for a timely first treatment, which is directly related to the preservation of functional visual acuity over a long period. The goal of this paper was to examine the correlation between the double-layer sign (DLS) and the presence of non-exudative macular neovascularization (MNV). Materials and Methods : Our research included 60 patients with AMD, exudative in one eye and non-exudative in the other eye. We analyzed only the non-exudative form using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). The patients were classified into three groups, depending on the duration of the disease (<2 years, 2 to 5 years, >5 years). The onset of the disease was deemed the moment of establishing a diagnosis of exudative AMD in one eye. We defined the presence or absence of a DLS using OCT and the presence of non-exudative MNV using OCT-A, both on 3 × 3 mm and 6 × 6 mm sections. DLS was used as a projection biomarker for non-exudative MNV, with the aim of establishing a rapid diagnosis and achieving early treatment of the disease. Results : We found that there was a statistically significant correlation between the DLS diagnosed using OCT and non-exudative MNV diagnosed by OCT-A for both 3 × 3 mm ( p < 0.001) and 6 × 6 mm ( p < 0.001) imaging. There was a statistically significant difference between the frequencies of both DLS and MNV in Groups I and III on both 3 × 3 and 6 × 6 mm imaging. A statistically significant difference was also noted in the frequencies of DLS and MNV on 6 × 6 mm imaging, but not on 3 × 3 mm imaging, between Groups I and II. No differences were found between the frequencies of DLS and MNV between Groups II and III. Conclusions : The DLS on OCT can be used as a projection biomarker to assess the presence of a non-exudative MNV.

Background and Objectives: The aim of the research was to investigate the differences in the concentrations of IL-12, IL-4, IL-10, and IFN-γ in tears after LASIK and PRK procedures., Materials and Methods: The study included 68 myopic eyes up to -3.0 D refractive spherical equivalent, divided into two groups: Group 1 LASIK ( n = 31) and Group 2 PRK ( n = 37). Three tear samples were taken from each eye: immediately before the procedure (t 0 ), 1 h after the procedure (t 1 ), and 24 h after the procedure (t 2 ). The concentrations of IL-12p70, IL-4, IL-10, and IFN-γ in the tear samples were determined by flow cytometry. Participants were not taking anti-inflammatory therapy 24 h after the procedure., Results: IL-4 levels 1 h after treatment did not differ between LASIK and PRK ( p = 0.990), while 24 h after PRK there was a significant decrease in IL-4 levels ( p < 0.05), but not after LASIK ( p = 0.476). In both the LASIK ( p < 0.05) and PRK ( p < 0.05) groups, there is an increase in IL-10 concentrations 1 h after treatment, which persists 24 h after LASIK ( p < 0.05) but not after PRK ( p = 0.081). There is an increase in IL-12p70 concentration 1 h after treatment in both the LASIK ( p < 0.001) and PRK groups ( p < 0.001). There is also an increase in IL-12p70 concentration 24 h after PRK ( p < 0.005), but not after LASIK ( p = 0.775)., Conclusions: IL-4 concentration shows a significantly higher value in the LASIK group than in the PRK group after 24 h. IL-10 and IL-12p70 levels increase one hour after surgery in both groups. After 24 h, the IL-10 levels remain elevated in the LASIK group, and the IL-12p70 levels remain elevated in the PRK group. Thus, LASIK and PRK procedures show different inflammatory dynamics.

Oxidative stress (OS) is involved in the pathogenesis of retinal neurodegenerative diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) and an important target of therapeutic treatments. New therapeutics are tested in vivo despite limits in terms of transferability and ethical concerns. Retina cultures using human tissue can deliver critical information and significantly reduce the number of animal experiments along with increased transferability. We cultured up to 32 retina samples derived from one eye, analyzed the model's quality, induced OS, and tested the efficiency of antioxidative therapeutics. Bovine, porcine, rat, and human retinae were cultured in different experimental settings for 3-14 d. OS was induced by a high amount of glucose or hydrogen peroxide (H 2 O 2 ) and treated with scutellarin, pigment epithelium-derived factor (PEDF), and/or granulocyte macrophage colony-stimulating factor (GM-CSF). The tissue morphology, cell viability, inflammation, and glutathione level were determined. The retina samples showed only moderate necrosis (23.83 ± 5.05 increased to 27.00 ± 1.66 AU PI-staining over 14 d) after 14 days in culture. OS was successfully induced (reduced ATP content of 288.3 ± 59.9 vs. 435.7 ± 166.8 nM ATP in the controls) and the antioxidants reduced OS-induced apoptosis (from 124.20 ± 51.09 to 60.80 ± 319.66 cells/image after the scutellarin treatment). Enhanced mammalian animal and human retina cultures enable reliable, highly transferable research on OS-triggered age-related diseases and pre-clinical testing during drug development.

Planning astigmatic correction is a complex task. Biomechanical simulation models are useful for predicting the effects of the physical procedure on the cornea. Algorithms based on these models allow preoperative planning and simulate the outcome of patient-specific treatment. The objective of this study was to develop a customised optimisation algorithm and determine the predictability of astigmatism correction by femtosecond laser arcuate incisions. In this study, biomechanical models and Gaussian approximation curve calculations were used for surgical planning. Thirty-four eyes with mild astigmatism were included, and corneal topographies were evaluated before and after femtosecond laser-assisted cataract surgery with arcuate incisions. The follow-up time was up to 6 weeks. Retrospective data showed a significant reduction in postoperative astigmatism. A total of 79.4% showed a postoperative astigmatic value less than 1 D. Clinical refraction was significantly reduced from -1.39 ± 0.79 D preoperatively to -0.86 ± 0.67 D postoperatively ( p 0.02). A positive reduction in topographic astigmatism was also observed ( p < 0.00). The best-corrected visual acuity increased postoperatively ( p < 0.001). We can conclude that customised simulations based on corneal biomechanics are a valuable tool for correcting mild astigmatism with corneal incisions in cataract surgery to improve postoperative visual outcomes.

Purpose: To compare the performance of Tecnis Eyhance ICB00 with Tecnis PCB00 IOL for far, intermediate, and near vision, in patients after bilateral cataract surgery., Settings: This study was done at Geneva University Hospitals., Design: This is a retrospective study of 224 eyes that underwent cataract between May 2019 and June 2020., Methods: Visual acuity was assessed from month 1 to 12 after surgery for distance, intermediate and near visual acuity, by the same optometrist, which was blind regarding the type of IOL. The patients answered to a quality of life questionnaire. Patients were excluded for: monocular surgery, macular disease, other IOL type, or inability to reach 20/20 visual acuity in both eyes without correction., Results: One hundred and fifty-two eyes were excluded. Three groups were then analyzed: PCB00 group (38 eyes), ICB00 group (22 eyes), and mismatch group (12 eyes). Monocular visual acuities (CIVA, UNVA and CNVA, in logMAR) were higher in the ICB00 group than the PCB00 group (respectively 0.3 vs 0.4, p = 0.0033; 0.3 vs 0.4, p = 0.0408; 0.3 vs 0.4, p = 0.0039). Binocular visual acuities, CIVA and CNVA were higher in the ICB00 group than the PCB00 group (0.2 vs 0.4, p = 0.0061; 0.15 vs 0.3, p = 0.018). This mirrored the findings of the quality of life questionnaire. There was no significant difference between PCB00 and mismatch groups., Conclusions: the Tecnis Eyhance was more effective for intermediate and near vision. The central defocus of the lens might help patients achieve spectacle independence and better quality of life.

Neovascular age-related macular degeneration (nvAMD) is characterized by choroidal neovascularization (CNV), which leads to retinal pigment epithelial (RPE) cell and photoreceptor degeneration and blindness if untreated. Since blood vessel growth is mediated by endothelial cell growth factors, including vascular endothelial growth factor (VEGF), treatment consists of repeated, often monthly, intravitreal injections of anti-angiogenic biopharmaceuticals. Frequent injections are costly and present logistic difficulties; therefore, our laboratories are developing a cell-based gene therapy based on autologous RPE cells transfected ex vivo with the pigment epithelium derived factor (PEDF), which is the most potent natural antagonist of VEGF. Gene delivery and long-term expression of the transgene are enabled by the use of the non-viral Sleeping Beauty (SB100X) transposon system that is introduced into the cells by electroporation. The transposase may have a cytotoxic effect and a low risk of remobilization of the transposon if supplied in the form of DNA. Here, we investigated the use of the SB100X transposase delivered as mRNA and showed that ARPE-19 cells as well as primary human RPE cells were successfully transfected with the Venus or the PEDF gene, followed by stable transgene expression. In human RPE cells, secretion of recombinant PEDF could be detected in cell culture up to one year. Non-viral ex vivo transfection using SB100X-mRNA in combination with electroporation increases the biosafety of our gene therapeutic approach to treat nvAMD while ensuring high transfection efficiency and long-term transgene expression in RPE cells.

Background : The aim of the study was to compare macular thickness behavior and clinical outcomes after femtosecond laser-assisted cataract surgery (FLACS) versus phacoemulsification conventional surgery (PCS). Methods : Macular Optical Coherence Tomography OCT was analyzed in 42 patients preoperatively, 1 day, 12 days, 4 weeks and 6 weeks postoperatively according to the 9-field Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Clinical findings were collected in both the FLACS group and the PCS group. Results : There was no significant difference in macular thickness between the FLACS and PCS groups ( p > 0.05). However, from postoperative day 12 onwards, there was a significant increase in macular thickness observed in both groups ( p < 0.001). In the FLACS group, a significant increase in visual acuity was observed on the first postoperative day, as compared to the PCS group ( p = 0.006). Conclusions : The use of a low-energy high-frequency femtosecond laser has potentially no effect on postoperative macular thickness. In the FLACS group, visual rehabilitation was significantly faster as compared to the PCS group. No complications occurred intraoperatively in either group.

(1) Background: Mid-stromal isolated Bowman layer transplantation aims to reduce and stabilize corneal ectasia in patients with advanced, progressive keratoconus. The purpose of this review is to evaluate the effectiveness and safety of this new surgical technique. (2) Methods: Following the PRISMA statement and checklist, we searched Medline, the Cochrane Controlled Trials Register, and Embase and used a broad systematic search strategy according to the Cochrane Collaboration. (3) Results: Eight studies with a total number of 120 eyes of 106 patients met our inclusion criteria. One month after Bowman layer transplantation, patients with keratoconus showed a significant decrease in the measured simulated keratometry (-4.74 D [95% CI -6.79 to -2.69]) and the maximum keratometry (-7.41 D [95% CI -9.64 to -5.19]), which remained significant one year postoperatively (-2.91 D [95% CI -5.29 to -0.53] and -5.80 D [-8.49 to -3.12]). Intra- and postoperative complications were observed in 3% and 9% of the patients, respectively. An estimated success rate of 75% to 85% was achieved by experienced surgeons at 5 to 8 years postoperatively. (4) Conclusions: Bowman layer transplantation may be an effective and safe treatment option in patients with advanced, progressive keratoconus. Additional multicenter prospective interventional studies are needed to confirm these preliminary findings.

We aimed to find out whether thin (≤500 μm) or normal (>500 μm, control) corneal thickness would impact efficacy and safety outcomes of small-incision lenticule extraction (SMILE). We retrospectively analyzed medical records of adult patients who had undergone SMILE. A total of 57 eyes were included in the “thin corneas” group and 180 eyes in the “control” group. At one month after surgery, rates of patients with uncorrected distance visual activity (UDVA) ≥ 0.8 were significantly higher in patients from the control group compared to the “thin corneas” group (87 vs. 71%, respectively p < 0.01), though rates were comparable at 3 months (87 vs. 76%, respectively, p > 0.05). SMILE had comparable safety in patients with thin and normal corneas. Procedure result predictability was comparable between groups. Regression analysis demonstrated that cap thickness impacted posterior corneal biomechanics, and the volume of removed tissue had a higher influence in patients with thin corneas. Moreover, an increase in cap thickness was associated with better final BCVA. Further study is needed for the evaluation of the impact of thin corneas on SMILE outcomes and planning. Our study also indicates that patients with thin corneas might require a different approach to nomogram calculation.

A broad range of CE applications from our organization is reviewed to give a flavor of the use of CE within the field of vaccine analyses. Applicability of CE for viral vaccine characterization, and release and stability testing of seasonal influenza virosomal vaccines, universal subunit influenza vaccines, Sabin inactivated polio vaccines (sIPV), and adenovirus vector vaccines were demonstrated. Diverse CZE, CE-SDS, CGE, and cIEF methods were developed, validated, and applied for virus, protein, posttranslational modifications, DNA, and excipient concentration determinations, as well as for the integrity and composition verifications, and identity testing (e.g., CZE for intact virus particles, CE-SDS application for hemagglutinin quantification and influenza strain identification, chloride or bromide determination in process samples). Results were supported by other methods such as RP-HPLC, dynamic light scattering (DLS), and zeta potential measurements. Overall, 16 CE methods are presented that were developed and applied, comprising six adenovirus methods, five viral protein methods, and methods for antibodies determination of glycans, host cell-DNA, excipient chloride, and process impurity bromide. These methods were applied to support in-process control, release, stability, process- and product characterization and development, and critical reagent testing. Thirteen methods were validated. Intact virus particles were analyzed at concentrations as low as 0.8 pmol/L. Overall, CE took viral vaccine testing beyond what was previously possible, improved process and product understanding, and, in total, safety, efficacy, and quality., (© 2021 Janssen Vaccines & Prevention B.V. Electrophoresis published by Wiley-VCH GmbH.)

Purpose: To evaluate the outcomes and safety of a minimally invasive technique for sutured IOL scleral fixation in case of compromised capsular and iris support., Materials and Methods: In this retrospective study, we explain our mini-invasive technique and assess the outcomes in terms of visual acuity, pre- or postoperative complications, and IOL position (Sensar AR40e, AMO) in a case series of three patients., Results: The expected best corrected visual acuity could be achieved after one month. Surgeries were uneventful with a stable eye. No postoperative complications occurred except for one patient who had a conjunctival disinsertion. Neither postoperative hypotony nor raised IOP was found. Additionally, no patient experienced corneal edema at one week control, IOL dislocation, vitreous hemorrhage, or new pupil's irregularity., Conclusions: In conclusion, each scleral technique has its own advantages and its inherent postoperative complications. To date, there is no evidence of superiority of any single technique. By improving our scleral sutured lens techniques, we could improve peroperative ocular stability, potentially decrease postoperative complication rate, and offer a rapid recovery with a stable visual acuity within a month., Competing Interests: The authors have no conflicts of interest., (Copyright © 2021 Mateusz Kecik et al.)

Background: The aim of the study is to investigate whether the circadian IOP rhythm can be influenced by combined cataract surgery with high frequency deep sclerotomy (HFDS) and whether intraocular pressure (IOP) can be significantly reduced by HFDS., Methods: In our study 10 patients were included, in whom 24 h IOP monitoring was installed before and after HFDS/cataract surgery using a Triggerfish. HFDS is a minimally invasive glaucoma surgery (MIGS)., Results: After performed HFDS combined with cataract surgery, the IOP was reduced from 27.7 ± 2.11 mmHg to 14.4 ± 2.59 mmHg, which is highly significant ( p < 0.001). The contact lens sensor (CLS) cosinor analysis pre- and postoperatively showed that the circadian rhythm is not influenced by the surgery, i.e., the circadian IOP rhythm did not show significant differences before and after surgery., Conclusions: HFDS combined with cataract surgery is a potent surgical method that can significantly reduce the IOP. However, the circadian rhythm cannot be changed by the surgery. The acrophase remained during the night in all patients.

The power density of femtosecond lasers and exposure time to the tissue are crucial for a successful procedure in terms of safety and precision. The reduction of the pulse duration allows reducing the quantity of the energy to be delivered to the tissue for disruption with strongly diminished mechanical and thermal collateral damage. The cutting effect of ultra-short pulses is very precise, minimally traumatic, safe, and predictable. Future developments will lead to further energy reductions to achieve optical breakdowns. However, the pulse length cannot be shortened arbitrarily because below 100 fs nonlinear effects can change the process in an unfavorable way. Compared to manual-conventional cataract surgery, femtosecond laser-assisted cataract surgery (FLACS) shows many advantages in clinical application, especially with regard to precision and tissue protection. The femtosecond laser has become particularly important and has made the overall procedure safer when we deal with complex cataract cases such as subluxated lenses. We provide an overview of the evolution of femtosecond laser technology for use in refractive and cataract surgeries. This article describes the advantages of available laser platforms with ultrashort pulses and mainly focuses on the technical and physical backgrounds of ophthalmic surgery technologies.

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.

Phacoemulsification is a widely used surgical method in cataract surgery with a high energy ultrasound source. The viscoelastic is considered to be tissue protective. The aim of this study is to investigate during surgery the impact of using viscoelastic versus no viscoelastic on clinical outcomes, potential complications and effect on endothelial cell density. The study group included 64 patients, who were subjected to phacoemulsification using balanced salt solution (BSS). Control group consisted of 62 patients, who underwent phacoemulsification using Hyaloronic acid 1% Healon 1%. Student's t -test was applied for statistical analysis. The simulations of temperature changes during phacoemulsification were performed by COMSOL Multiphysics software. In the BSS group, a mean endothelial cell loss (ECL) of 4.5% was measured one month postoperatively, while in the Healon group ECL was 5.3%. Data analysis showed no significant difference in ECL between the groups (Student's t -test, p = 0.8). No significant difference was observed in endothelial cell morphology and IOP between the two groups pre- and postoperatively (all p > 0.05). The modeling of thermo fluid dynamics showed that the heating of the cornea is slightly less when Healon was used as irrigation fluid. The phacoemulsification technique can be performed by an experienced surgeon with viscoelastics or continuous anterior chamber (AC) irrigation on the same level of safety regarding endothelial cell damage, providing equally satisfying clinical outcomes.

Background: It is known that pterygia above a certain size cause astigmatism and other aberrations of the human cornea and thus impair the quality of vision. Exclusive Sr-/Ytt-90 beta irradiation is a highly effective treatment for primary pterygia. The aim of this retrospective study is to determine the extent to which higher order corneal aberrations are affected by this treatment., Methods: Evaluation of corneal topographies and wavefront aberration data of 20 primary pterygia patients generated before and at different points in time in the first year after irradiation. Additionally, the size of the pterygium was measured., Results: The study showed a significant increase in coma and triple leaf aberrations in pterygia with a horizontal length of 2 mm and more. It was also found that a pterygium size greater than 2 mm significantly induces astigmatism. Both phenomena reduce visual quality. In none of the patients could a pterygium recurrence be detected after irradiation., Conclusions: If the pterygium size is less than 2 mm, early exclusive Sr/Ytt-90 beta irradiation can be recommended. If the size is more than 2 mm, a pterygium excision 6 months after beta irradiation can be discussed.

Femtosecond laser-assisted cataract surgery has the potential to make critical steps of cataract surgery easier and safer, and reduce endothelial cell loss, thus, improving postoperative outcomes. This study compared FLACS with the conventional method in terms of endothelial cells behavior, clinical outcomes, and capsulotomy precision., Methods: In a single-center, randomized controlled study, 130 patients with cataracta senilis received FLACS or conventional cataract surgery., Results: A significant endothelial cell loss was observed postoperatively, compared to the preoperative values in both groups. The endothelial cell counts was significantly better in the FLACS group in cataract grade 2 ( p = 0.048) patients, compared to conventionally at 4 weeks. The effective phaco time was notably shorter in grade 2 of the FLACS group ( p = 0.007) compared to the conventional. However, no statistically significant differences were found for the whole sample, including all cataract grades, due to the overall cataract density in the FLACS group being significantly higher (2.60 ± 0.58, p < 0.001) as compared to conventional methods (2.23 ± 0.42)., Conclusions: Low energy FLACS provides a better result compared to endothelial cell loss, size, and shape variations, as well as in effective phaco time within certain cataract grade subgroups. A complete comparison between two groups was not possible because of the higher cataract grade in the FLACS. FLACS displayed a positive effect on endothelial cell preservation and was proven to be much more precise.

Vaccines against infectious diseases are urgently needed. Therefore, modern analytical method development should be as efficient as possible to speed up vaccine development. The objectives of the study were to identify critical method parameters (CMPs) and to establish a set of steps to efficiently develop and validate a CE-SDS method for vaccine protein analysis based on a commercially available gel buffer. The CMPs were obtained from reviewing the literature and testing the effects of gel buffer dilution. A four-step approach, including two multivariate DoE (design of experiments) steps, was proposed, based on CMPs and was verified by CE-SDS method development for: (i) the determination of influenza group 1 mini-hemagglutinin glycoprotein; and (ii) the determination of polio virus particle proteins from an inactivated polio vaccine (IPV). The CMPs for sample preparation were incubation temperature(s) and time(s), pH, and reagent(s) concentration(s), and the detection wavelength. The effects of gel buffer dilution revealed the CMPs for CE-SDS separation to be the effective length, the gel buffer concentration, and the capillary temperature. The four-step approach based on the CMPs was efficient for the development of the two CE methods. A four-step approach to efficiently develop capillary gel electrophoresis methods for viral vaccine protein analysis was successfully established., (© 2020 The Authors. Electrophoresis published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Before the advent of modern tomographic imaging and corneal cross-linking (CXL), diagnosis and treatment of ectatic disease were limited to disease severity where changes on the anterior corneal surface lead to visual complaints. Rigid contact lenses and/or penetrating keratoplasty addressed late stage disease, as identifying early or subclinical disease was not possible, or its need appreciated. The emergence of CXL as a viable treatment to alter the natural progression of keratoconus heightened the need for improved diagnostics.Several methods have been described in the literature to evaluate and document progression in keratoconus, but there has been no consistent definition of ectasia progression. Newer imaging techniques (ie, tomography) allowed the detection of earlier ectatic disease, before visual loss and subjective complaints. The Belin ABCD classification/staging system was introduced on a Scheimpflug imaging system [Pentacam, (Oculus GmbH, Wetzlar, Germany)] to address previous shortcomings. The ABCD system utilizes 4 parameters: Anterior ("A") and posterior ("B" for Back) radius of curvature taken from a 3.0 mm optical zone centered on the thinnest point, "C" is minimal Corneal thickness, and "D" best spectacle Distance visual acuity. The first 3 parameters (A, B, C) are machine-generated objective measurements that can be used to determine progressive change.The staging system is not limited to a specific commercial entity and can be incorporated in any tomographic imaging system. The ABCD Progression Display graphically displays each parameter and shows when statistical change above measurement noise is reached. This should allow the clinician the ability to diagnose progressive disease at a much earlier stage than was previously possible, with the confidence that earlier intervention could prevent visual loss.

Background: To determine the average amount of mechanical forces applied to the lids of keratoconus patients during eye rubbing., Methods: Fifty-seven patients (41 male, 16 female, average age 34.8 years) with a clinically and topographically diagnosed keratoconus and a history of eye rubbing were prospectively asked to perform their individual eye rubbing movement on a high-precision balance. The type of eye-rubbing movement and the force applied, represented in newtons (N), were recorded and analyzed., Results: We detected three different types of eye rubbing. Rubbing with the fingertip was most frequent (51%), followed by rubbing with the knuckle (44%) and rubbing with the fingernail (6%). Each type of eye rubbing showed different average forces, with knuckle type eye rubbing applying significantly more force (9.6 ± 6.3 N) on the lids than fingertip (4.3 ± 3.1 N) and fingernail (2.6 ± 3.3 N) types (p < 0,001 and p = 0,016, respectively)., Conclusions: There were major variations in the force exerted on the lids, depending on the type of eye rubbing employed. This data will help determine the forces that need to be applied in future experimental eye rubbing models.

Purpose: To determine surgical parameters for arcuate keratotomy by simulating the intervention with a patient-specific model., Setting: University Eye Clinic Salzburg, Paracelsus Medical University, Austria, and Institute for Surgical Technology and Biomechanics, University of Bern, Switzerland., Design: Computational modeling study., Methods: A new approach to plan arcuate keratotomy based on personalized finite element simulations was developed. Using this numeric tool, an optimization algorithm was implemented to determine the incision parameters that best met the surgeon's requirements while preserving the orientation of the astigmatism. Virtual surgeries were performed on patients to compare the performance of the simulation-based approach with results based on the Lindstrom and Donnenfeld nomograms and with intrastromal interventions., Results: Retrospective data on 28 patients showed that personalized simulation reproduced the surgically induced change in astigmatism (Pearson correlation = 0.8). Patient-specific simulation was used to examine strategies for arcuate interventions on 621 corneal topographies. The Lindstrom nomogram resulted in low postoperative astigmatism (mean 0.03 diopter [D] ± 0.3 [SD]) but frequent overcorrections (20%). The Donnenfeld nomogram and intrastromal incisions resulted in a small amount of overcorrection (1.5%) but a wider spread in astigmatism (mean 0.63 ± 0.35 D and 0.48 ± 0.50 D, respectively). In contrast, the new numeric parameter optimization approach led to postoperative astigmatism values (mean 0.40 ± 0.08 D, 0.20 ± 0.08 D, and 0.04 ± 0.13 D) that closely matched the target astigmatism (0.40 D, 0.20 D, and 0.00 D), respectively, while keeping the number of overcorrections low (<1.5%)., Conclusion: Using numeric modeling to optimize surgical parameters for arcuate keratotomy led to more reliable postoperative astigmatism, limiting the risk for overcorrection., (Copyright © 2019 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Today there are different options for correcting presbyopia by corneal laser procedure, but all of them have their benefits and compromises. The Monovision is a pseudoaccommodation procedure which works with an anisometropy of up to 2 D. The smaller the anisometropy is the faster a neuroadaptation will be achieved. There could be a decrease of binocularity. The monovision is not well supported by all patients, thus it is important to simulate this correction by contact lenses before surgery. The PresbyLASIK is a corneal multifocal solution for presbyopia correction for emmetropic, myopic and hyperopic eyes. It is a true presbyopia procedure where both eyes will be treated for far, intermediate and near. The disadvantage and compromise is that in some cases there could be a loss of uncorrected visual acuity. The corneal inlay is a solution for emmetropic, presbyopic patients who have a strong intention to read without glasses. The disadvantages could be some side effects as halo, glare, decrease of contrast and far vision. All procedures are potentially reversible in case the patient does not support the correction. An enhancement is possible for Monovision and PresbyLASIK., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: The introduction of corneal cross-linking (CXL) with ultraviolet-A (UVA) and Riboflavin photosensitizer (Vit B 2 ) from Seiler et al. , revolutionized the treatment of Keratoconus and other corneal ectatic diseases. Today, the commonly known epithelium off Dresden protocol is in clinical use for the last 15 years with great success and regarded by many as the golden standard., Methods: With several studies demonstrating its simplicity, efficacy and safety this revolutionary method, paved the way for new therapies and strategies in the treatment of corneal ectatic diseases and changed our understanding in corneal biomechanics. Recent scientific and technological advances enabled the creation of various modifications of the initial CXL protocol and the formation of new ones., Conclusion: This work highlights the recent advances of CXL, such as the role of oxygen, higher fluence and shorter irradiation times as well as the various clinical applications and updates of this method.

Background: The aim of our study was to investigate the safety and efficacy of the LDV Z8 femtosecond laser in cataract surgery compared to the conventional procedure., Methods: This prospective study was performed at the Swiss Eye Research Foundation, Eye Clinic ORASIS, Reinach, Switzerland. The study included 130 eyes from 130 patients: 68 treated with femtosecond laser-assisted cataract surgery (FLACS) using the FEMTO LDV Z8 and 62 treated with conventional phacoemulsification. Capsulotomy and lens fragmentation in the laser group were performed with the FEMTO LDV Z8 femtosecond laser system, which employs a new, low-energy, high repetition rate laser process for cataract surgery. In the conventional group, the capsulotomy was performed by a cystotome, and lens fragmentation was achieved by the stop-and-chop., Results: Ease of phacoemulsification (on a 4-point scale), the completeness of capsulotomy (on a 10-point scale), effective phacoemulsification time (seconds), uncorrected distance visual acuity (UCVA), best spectacle-corrected distance visual acuity (BSCVA), spherical equivalent (SE), and safety of the procedure were evaluated. The total follow-up time was three months., Conclusions: FLACS with the FEMTO LDV Z8 system was characterized by complete and reproducible capsulotomy and highly effective lens fragmentation. Postoperative visual outcomes were excellent, and the safety of the procedure was optimal., Competing Interests: The authors declare no conflict of interest.

Laser Assisted in Situ Keratomileusis (LASIK) is a proven treatment method for corneal refractive surgery. Surgically induced higher order optical aberrations were a major reason why the method was only rarely used to treat presbyopia, an age-related near-vision loss. In this study, a novel customization algorithm for designing multifocal ablation patterns, thereby minimizing induced optical aberrations, was used to treat 36 presbyopic subjects. Results showed that most candidates went from poor visual acuity to uncorrected 20/20 vision or better for near (78%), intermediate (92%), and for distance (86%) vision, six months after surgery. All subjects were at 20/25 or better for distance and intermediate vision, and a majority (94%) were also better for near vision. Even though further studies are necessary, our results suggest that the employed methodology is a safe, reliable, and predictable refractive surgical treatment for presbyopia., Competing Interests: All authors declare no conflict of interest.

A prospective comparative study assessing the importance of the intra-operative dynamic rotational tracking-especially in the treatment of astigmatisms in corneal refractive Excimer laser correction-concerning clinical outcomes is presented. The cyclotorsion from upright to supine position was measured using iris image comparison. The Group 1 of patients was additionally treated with cyclorotational control and Group 2 only with X-Y control. Significant differences were observed between the groups regarding the mean postoperative cylinder refraction ( p < 0.05). The mean cyclotorsion can be calculated to 3.75° with a standard deviation of 3.1°. The total range of torsion was from -14.9° to +12.6°. Re-treatment rate was 2.2% in Group 1 and 8.2% in Group 2, which is highly significant ( p < 0.01). The investigation confirms that the dynamic rotational tracking system used for LASIK results in highly predictable refraction quality with significantly less postoperative re-treatments., Competing Interests: The authors declare no conflict of interest.

Pterygium is a vascularized, invasive transformation on the anterior corneal surface that can be treated by Strontium-/Yttrium90 beta irradiation. Finite element modeling was used to analyze the biomechanical effects governing the treatment, and to help understand clinically observed changes in corneal astigmatism. Results suggested that irradiation-induced pulling forces on the anterior corneal surface can cause astigmatism, as well as central corneal flattening. Finite element modeling of corneal biomechanics closely predicted the postoperative corneal surface (astigmatism error -0.01D; central curvature error -0.16D), and can help in understanding beta irradiation treatment. Numerical simulations have the potential to preoperatively predict corneal shape and function changes, and help to improve corneal treatments.

Image-based modeling is a popular approach to perform patient-specific biomechanical simulations. One constraint of this technique is that the shape of soft tissues acquired in-vivo is deformed by the physiological loads. Accurate simulations require determining the existing stress in the tissues or their stress-free configurations. This process is time consuming, which is a limitation to the dissemination of numerical planning solutions to clinical practice. In this study, we propose a method to determine the stress-free configuration of soft tissues using a Gaussian process (GP) regression. The prediction relies on a database of pre-calculated results to enable real time predictions. The application of this technique to the human cornea showed a level of accuracy five to ten times higher than the accuracy of the topographic device used to obtain the patients' anatomy; results showed that for almost all optical indices, the predicted curvature error did not exceed 0.025 D, while the wavefront aberration percentage error did not overcome 5%. In this context, we believe that GP models are suitable for predicting the stress free configuration of the cornea and can be used in planning tools based on patient-specific finite element simulations. Due to the high level of accuracy required in ophthalmology, this approach is likely to be appropriate for other applications requiring the definition of the relaxed shape of soft tissues., (Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.)