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Mike P Holzer,1 Rudy MMA Nuijts,2 Soraya MR Jonker,2 Erik LJG Mertens,3 Asim Bozkurt Sener,4 Jorge AO Cazal,5 Antoni Salvador Playa,5 Ramon Ruiz Mesa,6 Bettina C Thomas1 1Universitäts-Augenklinik Heidelberg, Heidelberg, Germany; 2Academisch Ziekenhuis Maastricht, Maastricht, the Netherlands; 3Medipolis, Antwerp, Belgium; 4Acibadem Maslak Hospital, Istanbul, Turkey; 5Hospital Universitari Mútua Terrassa, Barcelona, Spain; 6Oftalvist CIO Jerez, Cádiz, SpainCorrespondence: Mike P HolzerAugenzentrum Prof. Dr. Holzer & Prof. Dr. Rabsilber, Bahnhofstrasse 18, Weinheim, 69469, GermanyTel + 49 0 6201 87 87 24Email info@augenzentrum-holzer.dePurpose: To evaluate the safety and efficacy of a new multi-segmented refractive multifocal intraocular lens (IOL) after phacoemulsification and refractive lens exchange (RLE).Patients and Methods: In this prospective, multicenter clinical trial, 63 presbyopic subjects who had cataract or where RLE candidates were bilaterally implanted with the Precizon Presbyopia IOL (Ophtec BV, Groningen, the Netherlands) after phacoemulsification. The study was conducted at 6 clinical centers in Germany, the Netherlands, Belgium, Turkey and Spain. Subjects were evaluated at baseline and at 1 day, 1 week, 1 and 3 months postoperatively for monocular and binocular uncorrected (UDVA) and corrected distance visual acuity (CDVA), uncorrected (UIVA) and distance-corrected intermediate visual acuity (DCIVA), uncorrected (UNVA), corrected (CNVA) and distance-corrected near visual acuity (DCNVA), contrast sensitivity and quality of vision.Results: Three months postoperatively, binocular UDVA and CDVA of ≥ 20/40 was achieved in 98.4% (60/61) and 100%, respectively. Binocular UIVA and DCIVA of ≥ 20/40 was achieved in 96.7% (59/61) and 93.4% (57/61) respectively. Binocular UNVA, CNVA and DCNVA of ≥ 20/40 was achieved in 93.4% (57/61), 98.4% (60/61) and 95% (57/60) subjects, respectively. Complete spectacle independence was achieved in 80% (49/61) patients; 93% of patients reported that they were quite or very satisfied with the outcomes of the procedure.Conclusion: Precizon Presbyopia IOL implantation is a safe and effective method to provide good visual acuity at all distances in presbyopic and cataract patients.Keywords: presbyopia-correcting IOL, refractive lens exchange, cataract surgery, multifocal IOL

In May 2023, a 36-year-old carpenter complained of a sudden decrease in visual acuity in both eyes after his fourth COVID-19 vaccination. He underwent extensive evaluation by ophthalmological, neurological, and internal medicine specialists elsewhere, which was unremarkable, except for a computed tomography scan of his brain showing minor occipital calcifications. In 2021, he had been diagnosed with anterior basement membrane dystrophy and treated with phototherapeutic keratectomy (PTK) of the left eye, leading to significant postoperative haze. On referral in July 2023, slitlamp examination showed significant anterior basement membrane dystrophy in the right eye, whereas the left eye had an extensive central scar in the anterior stroma, measuring up to 6 mm in width and 140 µm in depth (Figures 1-3JOURNAL/jcrs/04.03/02158034-202410000-00017/figure1/v/2024-09-18T130724Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202410000-00017/figure2/v/2024-09-18T130724Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202410000-00017/figure3/v/2024-09-18T130724Z/r/image-tiff). His corrected distance visual acuity was 20/80 in his right eye and 20/200 in his left eye, with a manifest refraction of -0.50 -3.75 × 170 and +0.00 -4.75 × 180, respectively. Corneal Scheimpflug topography showed regular corneal astigmatism of 3.3 diopters (D) and 5.5 D in the right and left eyes, respectively, with a corneal thickness of 550 and 566 µm (Figure 4JOURNAL/jcrs/04.03/02158034-202410000-00017/figure4/v/2024-09-18T130724Z/r/image-tiff). The Schirmer tear test was 20-20 mm. Fundoscopy, electrophysiological testing, and retinal optical coherence tomography (OCT) showed no abnormalities. The patient mentioned he had Crohn disease, managed with ustekinumab (a monoclonal antibody inhibitor of cytokines interleukin [IL]-12 and IL-23), but he had discontinued it because of the apparent remission of the disease. Attempts to improve visual acuity involved a soft bandage contact lens in the right eye, which was discontinued after 2 days because of the occurrence of a small corneal infiltrate that healed with a short course of topical antibiotics. Unfortunately, because of his vision, he cannot perform his tasks as a carpenter anymore. Which is your recommended treatment for both eyes?, (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Background: Epidemiological and toxicological studies indicate that increased exposure to air pollutants can lead to neurodegenerative diseases. To further confirm this relationship, we evaluated the association between exposure to ambient air pollutants and corneal nerve measures as a surrogate for neurodegeneration, using corneal confocal microscopy., Methods: We used population-based observational cross-sectional data from The Maastricht Study including N = 3635 participants (mean age 59.3 years, 51.6% were women, and 19.9% had type 2 diabetes) living in the Maastricht area. Using the Geoscience and hEalth Cohort COnsortium (GECCO) data we linked the yearly average exposure levels of ambient air pollutants at home address-level [particulate matter with diameters of ≤ 2.5 µm (PM2.5), and ≤ 10.0 µm (PM10), nitrogen dioxide (NO2), and elemental carbon (EC)]. We used linear regression analysis to study the associations between Z-score for ambient air pollutants concentrations (PM 2.5 , PM 10 , NO 2 , and EC) and Z-score for individual corneal nerve measures (corneal nerve bifurcation density, corneal nerve density, corneal nerve length, and fractal dimension)., Results: After adjustment for potential confounders (age, sex, level of education, glucose metabolism status, corneal confocal microscopy lag time, inclusion year of participants, smoking status, and alcohol consumption), higher Z-scores for PM 2.5 and PM 10 were associated with lower Z-scores for corneal nerve bifurcation density, nerve density, nerve length, and nerve fractal dimension [stβ (95% CI): PM 2.5 -0.10 (-0.14; -0.05), -0.04 (-0.09; 0.01), -0.11 (-0.16; -0.06), -0.20 (-0.24; -0.15); and PM 10 -0.08 (-0.13; -0.03), -0.04 (-0.09; 0.01), -0.08 (-0.13; -0.04), -0.17 (-0.21; -0.12)], respectively. No associations were found between NO 2 and EC and corneal nerve measures., Conclusions: Our population-based study demonstrated that exposure to higher levels of PM 2.5 and PM 10 are associated with higher levels of corneal neurodegeneration, estimated from lower corneal nerve measures. Our results suggest that air pollution may be a determinant for neurodegeneration assessed in the cornea and may impact the ocular surface health as well., (© 2024. The Author(s).)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Commonly used methods for both clinical diagnosis of SARS-CoV-2 infection and management of infected patients involve the detection of viral RNA, but the presence of infectious virus particles is unknown. Viability PCR (v-PCR) uses a photoreactive dye to bind non-infectious RNA, ideally resulting in the detection of RNA only from intact virions. This study aimed to develop and validate a rapid v-PCR assay for distinguishing intact and compromised SARS-CoV-2. Propidium monoazide (PMAxx) was used as a photoreactive dye. Mixtures with decreasing percentages of intact SARS-CoV-2 (from 100% to 0%) were prepared from SARS-CoV-2 virus stock and a clinical sample. Each sample was divided into a PMAxx-treated part and a non-PMAxx-treated part. Reverse transcription-PCR (RT-PCR) using an in-house developed SARS-CoV-2 viability assay was then applied to both sample sets. The difference in intact SARS-CoV-2 was determined by subtracting the cycle threshold ( Ct ) value of the PMAxx-treated sample from the non-PMAxx-treated sample. Mixtures with decreasing concentrations of intact SARS-CoV-2 showed increasingly lower delta Ct values as the percentage of intact SARS-CoV-2 decreased, as expected. This relationship was observed in both high and low viral load samples prepared from cultured SARS-CoV-2 virus stock, as well as for a clinical sample prepared directly from a SARS-CoV-2 positive nasopharyngeal swab. In this study, a rapid v-PCR assay has been validated that can distinguish intact from compromised SARS-CoV-2. The presence of intact virus particles, as determined by v-PCR, may indicate SARS-CoV-2 infectiousness., Importance: This study developed a novel method that can help determine whether someone who has been diagnosed with coronavirus disease 2019 (COVID-19) is still capable of spreading the virus to others. Current tests only detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, but cannot tell whether the particles are still intact and can thus infect cells. The researchers used a dye that selectively blocks the detection of damaged virions and free RNA. They showed that this viability PCR reliably distinguishes intact SARS-CoV-2 capable of infecting from damaged SARS-CoV-2 or free RNA in both cultured virus samples and a clinical sample. Being able to quickly assess contagiousness has important implications for contact tracing and safely ending isolation precautions. This viability PCR technique provides a simple way to obtain valuable information, beyond just positive or negative test results, about the actual risk someone poses of transmitting SARS-CoV-2 through the air or surfaces they come into contact with., Competing Interests: The authors declare no conflict of interest.

Purpose: To compare web-based, self-administered follow-up after cataract surgery to conventional face-to-face follow-up., Setting: Eye clinics in the Netherlands, Austria, and Germany., Design: Randomized controlled trial with an embedded method comparison study (ClinicalTrials.gov: NCT04809402)., Methods: Routine patients with cataract were randomized into 2 groups: The telemonitoring group undertook web-based vision self-assessments and questionnaires from home, while the usual care group received conventional care. All participants had a 4- to 6-week postoperative clinic visit for safety and validation purposes. Outcomes included, the web test's accuracy for assessing postoperative visual acuity (VA) and refractive error, adverse event rates, and patient-reported outcome measurements (PROMs)., Results: 94 participants (188 eyes) were enrolled. Web-based uncorrected distance VA testing demonstrated a negligible mean difference (-0.03 ± 0.14 logMAR) when compared with conventional Early Treatment Diabetic Retinopathy Study chart testing, with 95% limits of agreement ranging from -0.30 to 0.24 logMAR. The web-based refraction assessment overestimated the postoperative refractive error (mean difference in spherical equivalent 0.15 ± 0.67 diopters), resulting in a poorer corrected distance VA compared with subjective refraction (mean 0.1 vs -0.1 logMAR). Rates of adverse events and unscheduled consultations were minimal across both groups. Preoperative and postoperative PROM questionnaires had a 100% response rate. Visual functioning (Catquest-9SF and National Eye Institute Visual Function Questionnaire-25) improved postoperatively (mean improvement -0.80 and 16.70, respectively) and did not significantly differ between the 2 groups., Conclusions: The patients with cataract in this study effectively provided postoperative outcome data using a web interface. Both conventional and web-based follow-ups yielded similar PROMs and adverse event rates. Future developments should reduce the variability in the web-based VA test and yield representative refraction outcomes., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

Purpose: We describe a patient after customized crosslinking (CXL) for progressive keratoconus who developed corneal edema with spontaneous resolution., Observations: A 24-year-old male with progressive keratoconus of the left eye underwent a customized CXL procedure with a total energy of 10 J/cm 2 for 16.4 minutes. Preoperative corrected distance visual acuity (CDVA) was 20/30 with a maximum keratometry (K)-value of 58.6 diopter (D) and the thinnest point measured 414 μm. The preoperative endothelial cell density (ECD) was 2414 cells/mm 2 . During treatment, corneal thickness was 325 μm after epithelial debridement and 375 μm after the application of 0.1 % riboflavin containing HPMC. After the treatment, antibiotic and steroid drops were prescribed for 5 days and 3 weeks, respectively. At the 1-month post-CXL visit the patient had no complaints, visual acuity and clinical examination showed no irregularities. At the 4-months post-CXL visit the patient complained of blurry vision. The CDVA was 20/100 and slit-lamp examination showed microcystic corneal edema. The corneal thickness at the thinnest point measured 440 μm. One month later the edema had resolved spontaneously and CDVA had restored to 20/25. Corneal thickness at the thinnest point measured 415 μm, the ECD was 1514 cells/mm 2 and confocal microscopy showed normal structural changes in the anterior stroma after CXL, with the demarcation line located at a depth of 414 μm, just above the corneal endothelium., Conclusions and Importance: We report a case of corneal edema following customized CXL with endothelial cell loss that resolved spontaneously. We recommend either adhering to a minimal stromal thickness of 400 μm before administering UV-A irradiation, using a contact lens or adjusting the irradiation to prevent this complication., Competing Interests: M.M. Dickman: Carl-Zeiss: consultant. R.M.M.A. Nuijts: Alcon: consultant, research grant; 10.13039/100005565Johnson & Johnson: consultant; Théa Pharma: consultant; 10.13039/100007569Carl-Zeiss: consultant; Teleon: research grant The other authors have no financial disclosures or competing interests., (© 2024 The Authors.)

Purpose: To compare the prediction accuracy of toric intraocular lens calculations using estimated vs measured posterior corneal astigmatism (PCA)., Design: Retrospective case series., Methods: A total of 110 eyes of 110 patients with uncomplicated toric intraocular lens implantation were included in this study. Predicted postoperative refractive astigmatism was calculated with the Barrett Toric Calculator using the estimated PCA (E-PCA), the measured IOLMaster 700 PCA (I-PCA), and the measured Pentacam PCA (P-PCA). Refractive astigmatism prediction errors (RA-PEs), including their trimmed (tr-) centroid (mean vector), spread (precision), tr-mean absolute RA-PE (accuracy), and percentage within a certain threshold, were determined using vector analysis and compared between groups., Setting: University Eye Clinic, Maastricht University Medical Center+, the Netherlands., Results: The tr-centroid RA-PEs of the E-PCA (0.02 diopter [D] at 82.2°), the I-PCA (0.08 D at 35.5°), and the P-PCA (0.09 D at 69.1°) were significantly different from each other (P < .01), but not significantly different from zero (P = .75, P = .05, and P = .05, respectively). The E-PCA had the best precision (tr-mean 0.40 D), which was not significantly lower than the I-PCA (0.42 D, P = .53) and P-PCA (0.43 D, P = .06). The E-PCA also had the best accuracy (0.40 D), which was not significantly different from the I-PCA (0.42 D, P = .26) and significantly better than the P-PCA (0.44 D, P < .01). The precision and accuracy of the I-PCA did not significantly differ from those of the P-PCA. There were no statistically significant differences in the percentage of eyes within a certain absolute RA-PE threshold., Conclusions: The Barrett Toric Calculator using the E-PCA, I-PCA, or P-PCA showed a comparable prediction of postoperative refractive astigmatism in standard clinical practice., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To adapt the Quality of Vision Questionnaire (QoV) for measuring negative dysphotopsia and to validate the original and modified versions in the Dutch population., Methods: The QoV was translated into Dutch according to standardized methodology. Negative dysphotopsia items were constructed based on focus group interviews, literature review and clinical data. The questionnaire was completed by 404 subjects, including contact lens wearers, patients with cataract and after cataract surgery (95.5% with a monofocal, 4.5% with a multifocal intraocular lens). Rasch analysis was applied for evaluation of reliability and validity of the original QoV and modified version, Negative Dysphotopsia QoV (ND-QoV)., Results: The frequency, severity and bothersome scales of the QoV and ND-QoV demonstrated good measurement precision, good fit statistics for all but one item, but significant mistargeting of more than one logit. Item estimations were stable across the study groups and scales were unidimensional with more than 50% of variance explained by the measurements. There was a positive correlation between questionnaire scores and best corrected visual acuity (r = 0.3, p < 0.01). The quality of vision measured by all three scales was significantly poorer (p < 0.01) in patients with negative dysphotopsia compared to asymptomatic pseudophakic patients., Conclusion: The Dutch version of the QoV questionnaire has shown good psychometric properties comparable to the native version as well as good reliability and validity. The addition of negative dysphotopsia items is a valuable modification for the reliable assessment of quality of vision in pseudophakic patients., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Stevens-Johnson syndrome (SJS) is characterised as an immuno-inflammatory condition with potentially blinding ocular sequelae. Therefore, we have investigated the ocular surface immune cell profile and correlated it with secreted tear molecular factors and clinical ocular sequelae in SJS patients., Methods: 21 patients (42 eyes) with chronic ocular SJS and 16 healthy controls (20 eyes) were included in the study. Severity, types of keratopathies and ocular surface (OS) manifestations were determined. OS wash samples from study subjects were used to determine the status of 13 immune cell subsets using flow cytometry. Levels of 42 secreted immuno-inflammatory factors were measured by flow cytometry-based multiplex ELISA in tear samples., Results: Neutrophils (Total, activated), neutrophils/NK cells ratio, neutrophils/T cells ratio were significantly (p < 0.05) elevated in SJS, while, proportions of T cells and NKT cells were significantly lower in SJS patients. Positive association between neutrophils and chronic ocular surface complication score (COCS) was observed, whereas, a negative association was noted between NK cells and COCS. Tear fluid levels of IL-6, IL-8, IL-18, IFNα/β/γ, TNFα, LIF, IL-8, HGF, sTNFR-I, NGAL, Granzyme, Perforins, MMP9/TIMP1 ratio were significantly higher in SJS. Loss of Limbal niche correlated significantly with immune profile and clinical sequelae. Increased neutrophils, decreased NK cells and specific set of altered secreted immuno-inflammatory mediators including bFGF, and IL-8 were observed in SJS patients with different types of keratopathies compared to those without keratopathy., Conclusion: Distinct ocular surface immune profile variations were observed to correlate with clinical stages of chronic ocular SJS. Our findings uncover novel mechanisms and potential for targeted therapy in chronic ocular SJS patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The intraoperative optical coherence tomography (iOCT) is recently introduced in Descemet membrane endothelial keratoplasty (DMEK) surgery, which aims to increase clinical performance and surgery safety. However, the acquisition of this modality is a substantial investment. The objective of this paper is to report on the cost-effectiveness of an iOCT-protocol in DMEK surgery with the Advanced Visualization in Corneal Surgery Evaluation (ADVISE) trial. This cost-effectiveness analysis uses data 6 months postoperatively from the multicentre prospective randomized clinical ADVISE trial. Sixty-five patients were randomized to usual care (n = 33) or the iOCT-protocol (n = 32). Quality-Adjusted Life Years (EQ-5D-5L), Vision-related Quality of Life (NEI-VFQ-25) and self-administered resources questionnaires were administered. Main outcome is the incremental cost-effectiveness ratio (ICER) and sensitivity analyses. The iOCT protocol reports no statistical difference in ICER. For the usual care group compared with the iOCT protocol, respectively, the mean societal costs are €5027 compared with €4920 (Δ€107). The sensitivity analyses report the highest variability on time variables. This economic evaluation learned that there is no added value in quality of life or cost-effectiveness in using the iOCT protocol in DMEK surgery. The variability of cost variables depends on the characteristics of an eye clinic. The added value of iOCT could gain incrementally by increasing surgical efficiency, and aiding in surgical decision-making., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

A 28-year-old nurse had an aberration-free femto-laser in situ keratomileusis (LASIK) performed for her myopia of -6.25 -0.50 × 096 and -6.75 -0.50 × 175 in the right and left eye, respectively. Corrected distance visual acuity (CDVA) preoperatively was 20/16. Preoperatively, there were no abnormalities on Scheimpflug imaging, and a pachymetry of 585 μm was measured in both eyes. Flap thickness was 115 μm. The patient was quite nervous during the surgery. Since the surgery, her uncorrected distance visual acuity (UDVA) and CDVA are suboptimal at 20/30 and 20/20 in the right eye, and 20/20 and 20/16 in the left eye. 3 months postoperatively, there is a stable manifest refraction of +0.25 -1.25 × 030 and +0.25 -0.00 × 0. The keratometric astigmatism in the Scheimpflug imaging is 1.2 diopter (D) × 114 and 0.4 D × 78 in the right and left eyes, respectively (FIgures 1 and 2). Thinnest pachymetry is 505 μm and 464 μm in the right and left eye, respectively. Her wavefront analysis shows refraction in a 6 mm zone of -0.99 -1.22 × 32 and -0.91 -0.36 × 136. The cycloplegic refraction is 1.25 -1.00 × 023 and +1.00 -0.25 × 006 (Figures 3 and 4). What is the cause of the suboptimal visual outcome in this case? What would be your treatment strategy to improve visual outcome?, (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: To compare the accuracy of nine conventional and newer-generation formulae in calculating intraocular lens power in eyes with axial myopia., Setting: Tertiary eye care center, Bengaluru, India., Design: Retrospective cross-sectional, comparative study conducted in India., Methods: Patients undergoing uneventful phacoemulsification in eyes with axial length >26 mm were included. Preoperative biometry was done using Lenstar LS 900 (Haag-Streit AG, Switzerland). Single eye of patients undergoing bilateral implantation was randomly selected. Optimized lens constants were used to calculate the predicted postoperative refraction of each formula, which was then compared with the actual refractive outcomes to give the prediction errors, following which subgroup analysis was performed. The Kane formula, Barrett universal II, Emmetropia Verifying Optical (EVO) 2.0, Hill Radial Basis Function (Hill RBF) 3.0, Olsen formula, along with Wang Koch-adjusted four formulae, that is, Sanders Retzlaff Kraff/Theoretical (SRK/T), Holladay 1, Haigis, and Hoffer Q formula, were compared for intraocular lens power calculations., Results: One hundred and sixty-five eyes that fulfilled all the inclusion criteria were studied. Hill RBF 3.0 had the lowest mean and median absolute prediction errors (0.355 and 0.275, respectively) compared to all formulas. In subgroup analysis (26-28, >28-30, and >30 mm), significant difference was seen only in extremely long eyes (>30 mm). The Hill RBF 3.0 formula generated the maximum percentage of eyes with refractive errors within ±0.25, ±0.5, ±0.75, and ±1 D (46%, 76.2%, 89.9%, and 95.8%, respectively)., Conclusion: This is the first study evaluating all the formulas exclusively in the myopic eyes. Hill RBF 3 was found to be superior in accuracy to all other formulas., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Purpose: To assess the effect of change in ocular spherical aberration (SA) with adaptive optics on visual acuity (VA) at different defocus after implantation of extended depth-of-focus (EDOF) and enhanced monofocal intraocular lenses (IOLs)., Settings: Narayana Nethralaya Eye Hospital, Bangalore, India., Design: Prospective, longitudinal, observational., Methods: 80 eyes (40 patients) that had cataract surgery were included in the study. 40 eyes were implanted with Eyhance EDOF IOLs and the remaining with Vivity EDOF IOLs. Baseline ocular aberrations were measured with a visual adaptive optics aberrometer, then the optimal SA was determined by increasing it in steps of -0.01 μm up to -0.1 μm until the maximum improvement in near distance VA was observed for a given eye. Then the defocus curve for each eye was measured after modifying the ocular SA by magnitude equal to optimal SA., Results: Most of the eyes accepted a negative induced SA of -0.05 μm (Eyhance group: 67.6%; Vivity group, 45.2%). In the Eyhance group (dominant eyes), VA improved at -2 diopters (D) ( P < .02) only and degraded at 0 D, +0.5 D, and +1 D defocus ( P < .05). In the Vivity group, the VA remained unchanged at all defocus ( P > .05). In the Eyhance group (nondominant eyes), VA improved at -3.5 D defocus only and degraded at +1.5 D and +2 D defocus ( P < .05). In the Vivity group, VA improved at -2.5 D defocus ( P < .05) only., Conclusions: A negative induced SA of -0.05 μm in implanted eyes was optimal for a slight improvement in distance-corrected near and intermediate VA without any significant decrease in baseline distance-corrected VA., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: One of the many consequences of the COVID-19 pandemic was a worldwide lockdown of ophthalmic surgery procedures for several months in 2020. The present study aims to answer the following question: does an intermission of cataract surgery for two months cause an increase in complication rates?, Methods: In this retrospective clinical chart review, data was taken from Dutch cataract complication registration database that contains pre-, intra- and postoperative information of patients that underwent cataract surgery in the Netherlands. The amount as well as type of complications were extracted before and after the eight weeks surgical intermission period (SIP): six weeks before (SIP-6) and six weeks after this period (SIP+6) for the years 2016-2020., Results: A significant decrease in complication rates was found between SIP-6 and SIP+6 in 2020. When SIP+6 2020 is compared to SIP+6 2019, a significant reduction is found. Overall, a downward trend in complication rates was observed in the period 2016-2020., Conclusion: A two-months intermission of performing elective cataract surgery does not cause an increase in complications. In contrast, we observe a reduction of postoperative complications. This implicates that refraining from cataract surgery for two months might not compromise operative skills. The possible downward trend over the years can be partially explained by improved training, education and equipment, as well as an increased use of intracameral antibiotics during operation. Possible explanations for the reduction of complications after lockdown could be decreased time pressure as a consequence of a reduced number of operations at the restart of surgeries, and heightened awareness and cautiousness when resuming the operations., (© 2023. The Author(s).)

Introduction: Allogeneic serum from blood donors is starting to be used to treat patients with dry eye disease (DED). However, the optimal dose is not known. We therefore aimed to evaluate the clinical efficaciousness and user-friendliness of micro-sized versus conventional-sized allogeneic serum eye drops (SEDs)., Methods: In a randomized trial, patients with DED first receive micro-sized SEDs (7 µl/unit) for 1 month, followed by a 1-month washout, before receiving conventional-sized SEDs (50 µl/unit) for 1 month; or vice versa. The primary endpoint was the Ocular Surface Disease Index (OSDI) score. Secondary endpoints were tear break-up time (TBT), tear production (TP), and presence of corneal punctate lesions (CP). The user-friendliness of both application systems was also compared. A linear mixed model for cross-over design was applied to compare both treatments., Results: Forty-nine patients completed the trial. The mean OSDI score significantly improved from 52 ± 3 to 41 ± 3 for micro-sized SEDs, and from 54 ± 3 to 45 ± 3 for conventional-sized SEDs. Non-inferiority (margin = 6) of micro-sized SEDs was established. We demonstrate a significant improvement for TBT in case of conventional-sized SEDs and for CP in both treatment groups. TP trended towards an improvement in both treatment groups. The user-friendliness of the conventional drop system was significantly higher., Conclusions: For the first time, non-inferiority of micro-sized allogeneic SEDs was established. The beneficial effect of both SED volumes was similar as measured by the OSDI score. Although user-friendliness of the micro drop system was significantly lower, it is an attractive alternative as it saves valuable donor serum., Trial Registration: ClinicalTrials.gov (NCT03539159)., (© 2023. The Author(s).)

Purpose: Keratoconus is characterized by the progressive thinning of the cornea, which leads to a cone-like appearance of the eye over time. Although conventionally defined as a noninflammatory condition, a number of recent studies have associated keratoconus (KC) with allergic conjunctivitis (AC) based on clinical parameters. This study aimed to consolidate this association by performing a proteomic analysis of tear fluid from patients with keratoconus and/or allergic conjunctivitis., Methods: Of 51 patients, 17 were diagnosed with KC, 17 were diagnosed with AC, and 17 were diagnosed with both KC and AC (combined). Nine of 34 patients with KC had a progressive form of the disease. Tear fluid samples (n = 51, one eye per patient) were collected by the Schirmer's strips. Tear proteins were extracted from the Schirmer's strips. Proteomic profiling of 384 inflammatory proteins was assessed by a multiplex proximity extension assay (Olink Explore 384 Inflammation Panel I)., Results: A total of 384 inflammatory proteins were measured. Two hundred seventy-two of the 384 proteins passed stringent data cleaning and were compared among the patient groups. Compared to the 2 other groups, LGALS9 was upregulated uniquely in KC, whereas FGF19, PDGFB, HPCAL1, OSM, and FCAR were downregulated in KC. Similarly, TNFRSF4 and CCL13 were specifically upregulated in AC, whereas ectodysplasin A receptor (EDAR) was uniquely downregulated in AC., Conclusions: High-throughput proteomic profiling of tear fluid confirms the association between KC and AC on a molecular level and raise the importance of redefining KC as an inflammatory condition.

Purpose: To define the external scleral sulcus (ESS) on a Scheimpflug image and use it for a morphometric analysis of corneal diameter (CD)., Design: Retrospective, cross-sectional study of pediatric Asian-Indian eyes., Methods: One random eye of 353 subjects between 5 and 18 years underwent 25-scan Pentacam HR imaging. For all scans, densitometry values along the anterior corneal edge were recorded and differentiated. The peaks on the differentiated curve were chosen as the ESS points, and this distance between them was called CD. Vertical (vCD), maximum (maxCD), minimum (minCD) CD and their meridians were defined. Multiple regression models (MRMs) with CD and other Pentacam parameters were built to predict astigmatism and its axis, mean keratometry (Kmean), and Belin/Ambrósio enhanced ectasia display deviation (BAD-D). MRMs were validated using intraclass correlation coefficient (ICC). Estimated horizontal CD (hCD) was validated against digital caliper measurement using ICC., Results: The ICC (95% CI) between caliper and hCD was 0.96 (0.93, 0.97). MRM predictions (P < .001) used CD parameters, anterior chamber depth, corneal volume and distance from the corneal thinnest location to apex. These predictions achieved an ICC of 0.34 (0.18, 0.46), 0.82 (0.78, 0.86), 0.87 (0.84, 0.89), and 0.81 (0.76, 0.84), respectively. The astigmatism axis prediction depended on the minCD and maxCD meridians. Its within-subject SD (4.97°) was less than 2 consecutive Pentacam scan angles (7.2°)., Conclusions: The CD metric strongly correlated with the astigmatism axis, keratometry, and BAD-D. Its spatial description may be significant in corneal treatment planning and disease diagnoses., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to analyze real-world practice patterns and graft survival after corneal transplantation for infectious keratitis in the Netherlands., Methods: All consecutive keratoplasties for infectious keratitis registered in the Netherlands Organ Transplant Registry were included. Graft survival was analyzed using Kaplan-Meier survival curves with Cox regression to compare the 3 most common pathogens with subgroup analysis for type and reason of transplantation, sex, and graft size. Multivariable analysis was performed using the same explanatory factors., Results: Between 2007 and 2017, 1111 keratoplasties for infectious keratitis were registered in the Netherlands Organ Transplant Registry. The most common pathogens were viruses (n = 437), bacteria (n = 271), and Acanthamoeba (n = 121). Human leukocyte antigen (HLA) matching did not provide a significant survival benefit, whereas emergency procedures showed worse graft survival [hazard ratio (HR) = 0.40, P = 0.120; HR = 2.73, P < 0.001, respectively]. Graft size >8.5 mm was significantly worse than graft size 8.5 mm (HR = 2.062, P = 0.010). In therapeutic keratoplasty, graft survival was significantly worse for Acanthamoeba than viral keratitis (HR = 2.36, P = 0.008). In the multivariable model, adjusting for graft size, type, and reason for transplantation, viral and bacterial keratitis did not differ significantly in graft survival, and Acanthamoeba showed a significantly worse prognosis (vs. viral keratitis, HR = 2.30, P < 0.001; bacterial keratitis, HR = 2.65, P < 0.001)., Conclusions: Viral keratitis was the most common indication for transplantation, followed by bacterial and Acanthamoeba keratitis. HLA matching did not offer protection over elective non-HLA-matched procedures, whereas emergency procedures and grafts sized >8.5 mm showed poor survival. In optical keratoplasty, survival is high for all pathogens, whereas in therapeutic keratoplasty Acanthamoeba shows poor outcome., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims/hypothesis: To assess the associations between glucose metabolism status and a range of continuous measures of glycaemia with corneal nerve fibre measures, as assessed using corneal confocal microscopy., Methods: We used population-based observational cross-sectional data from the Maastricht Study of N=3471 participants (mean age 59.4 years, 48.4% men, 14.7% with prediabetes, 21.0% with type 2 diabetes) to study the associations, after adjustment for demographic, cardiovascular risk and lifestyle factors, between glucose metabolism status (prediabetes and type 2 diabetes vs normal glucose metabolism) plus measures of glycaemia (fasting plasma glucose, 2 h post-load glucose, HbA 1c , skin autofluorescence [SAF] and duration of diabetes) and composite Z-scores of corneal nerve fibre measures or individual corneal nerve fibre measures (corneal nerve bifurcation density, corneal nerve density, corneal nerve length and fractal dimension). We used linear regression analysis, and, for glucose metabolism status, performed a linear trend analysis., Results: After full adjustment, a more adverse glucose metabolism status was associated with a lower composite Z-score for corneal nerve fibre measures (β coefficients [95% CI], prediabetes vs normal glucose metabolism -0.08 [-0.17, 0.03], type 2 diabetes vs normal glucose metabolism -0.14 [-0.25, -0.04]; linear trend analysis showed a p value of 0.001), and higher levels of measures of glycaemia (fasting plasma glucose, 2 h post-load glucose, HbA 1c , SAF and duration of diabetes) were all significantly associated with a lower composite Z-score for corneal nerve fibre measures (per SD: -0.09 [-0.13, -0.05], -0.07 [-0.11, -0.03], -0.08 [-0.11, -0.04], -0.05 [-0.08, -0.01], -0.09 [-0.17, -0.001], respectively). In general, directionally similar associations were observed for individual corneal nerve fibre measures., Conclusions/interpretation: To our knowledge, this is the first population-based study to show that a more adverse glucose metabolism status and higher levels of glycaemic measures were all linearly associated with corneal neurodegeneration after adjustment for an extensive set of potential confounders. Our results indicate that glycaemia-associated corneal neurodegeneration is a continuous process that starts before the onset of type 2 diabetes. Further research is needed to investigate whether early reduction of hyperglycaemia can prevent corneal neurodegeneration., (© 2023. The Author(s).)

Purpose: To evaluate the performance of different probabilistic classifiers to predict posterior capsule rupture (PCR) prior to cataract surgery., Methods: Three probabilistic classifiers were constructed to estimate the probability of PCR: a Bayesian network (BN), logistic regression (LR) model, and multi-layer perceptron (MLP) network. The classifiers were trained on a sample of 2 853 376 surgeries reported to the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO) between 2008 and 2018. The performance of the classifiers was evaluated based on the area under the precision-recall curve (AUPRC) and compared to existing scoring models in the literature. Furthermore, direct risk factors for PCR were identified by analysing the independence structure of the BN., Results: The MLP network predicted PCR overall the best (AUPRC 13.1 ± 0.41%), followed by the BN (AUPRC 8.05 ± 0.39%) and the LR model (AUPRC 7.31 ± 0.15%). Direct risk factors for PCR include preoperative best-corrected visual acuity (BCVA), year of surgery, operation type, anaesthesia, target refraction, other ocular comorbidities, white cataract, and corneal opacities., Conclusions: Our results suggest that the MLP network performs better than existing scoring models in the literature, despite a relatively low precision at high recall. Consequently, implementing the MLP network in clinical practice can potentially decrease the PCR rate., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The aim of this study was to explore video-graded intraoperative risk factors for graft detachment (GD) and rebubbling in Descemet membrane endothelial keratoplasty surgery., Methods: A post hoc analysis of 65 eyes of 65 pseudophakic subjects with Fuchs endothelial dystrophy that underwent Descemet membrane endothelial keratoplasty surgery as part of the Advanced Visualization In Corneal Surgery Evaluation trial. All surgical recordings were assessed by 2 graders using a structured assessment form. A multinominal regression was performed to estimate the independent effect of video-graded intraoperative factors on the incidence of GD and rebubbling. Secondary outcomes are corrected distance visual acuity and endothelial cell density., Results: In total, 33 GDs were recorded, of which 17 required rebubbling. No significant predictors for GD or rebubbling were identified. However, the results revealed 2 clinically relevant patterns. An unfavorable graft configuration (ie, wrinkled, tight scroll, or taco-shaped) and a gas-bubble size smaller than the graft diameter were associated with an increased risk of GD [odds ratio (OR) 2.5 and OR 2.26, respectively] and rebubbling (OR 2.0 and OR 2.60, respectively). Inversely, a larger gas-bubble size was associated with a reduced risk of GD (OR 0.37) and rebubbling (OR 0.36). At 3 and 6 months postoperatively, corrected distance visual acuity was poorer in subjects requiring a rebubbling and endothelial cell density loss was higher in subjects with a partial GD., Conclusions: Our analysis revealed that the gas-bubble size and graft shape/geometry seem to be relevant clinical factors for GD and rebubbling, whereas descemetorhexis difficulty, degree of graft manipulation, graft overlap, and surgical iridectomy were not associated with an increased risk., Competing Interests: Conflicts of interest statement: The authors have no conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Alzheimer's disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive or expensive, and not available in each hospital, thus limiting their usage as a front-line screener. The TearAD study aims to use tear fluid as a potential source for AD biomarkers. In previous reports, we demonstrated that AD biomarkers amyloid-beta and tau, are measurable in tear fluid and are associated with disease severity and neurodegeration. This study aims to validate previous results in a larger cohort and evaluate the diagnostic accuracy of tear biomarkers to discriminate between individuals with and without neurodegeneration as determined by hippocampal atrophy., Methods: The TearAD study is an observational longitudinal multi-center study that will enroll 50 cognitively healthy controls, 50 patients with subjective cognitive decline, 50 patients with mild cognitive impairment and 50 patients with AD dementia from the memory clinic. Participants will be examined at baseline, after one year, and after two years follow-up. Study assessments include neuropsychological tests and ophthalmic examination. All participants will receive a MRI scan, and a subset of the study population will undergo cerebral spinal fluid collection and an amyloid PET scan. Tear fluid will be collected with Schirmer strips and levels of Aβ38, Aβ40, Aβ42, t-tau and p-tau in tear fluid will be determined using multiplex immunoassays. Blood samples will be collected from all participants. Images of the retina will be obtained with a standard, hyperspectral and ultra-wide field fundus camera. Additionally, macular pigment optical density will be measured with the macular pigment reflectometer, and cross-sectional images of the retina will be obtained through optical coherence tomography imaging., Discussion: The TearAD study will provide insight into the potential diagnostic use of tear biomarkers as a minimally invasive and low cost tool for the screening and diagnosis of AD., Trial Registration: Retrospectively registered at clinicaltrials.gov (NCT05655793)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: To present the results of a study investigating the 3-year effectiveness and safety of the Clareon single-piece intraocular lens (IOL)., Setting: 19 multinational sites., Design: Prospective multicenter single-arm study., Methods: Patients were bilaterally implanted with Clareon IOLs. Assessments included uncorrected distance visual acuity, corrected distance visual acuity (CDVA), manifest refraction, tilt, decentration, applanation tonometry, and fundus examination, including glistenings and posterior capsule opacification (PCO) evaluation. The primary outcomes for effectiveness and safety were evaluated at 1 year and compared with ISO historical safety and performance endpoint (SPE) rates. Patients were followed for up to 3 years after implantation., Results: 424 eyes of 215 patients were implanted (n = 215 first eye, n = 209 second eye), and 183 patients completed the trial at 3 years (with 364 binocular and 1 monocular patient). At 1 year, the cumulative and persistent adverse event rates were below SPE targets, and 99.5% of eyes achieved a monocular CDVA of ≤0.3 logMAR (vs the SPE target of 92.5%). At 3 years, the mean monocular CDVA was -0.032, with 93.4% (341/365) of eyes achieving a CDVA of 0.1 logMAR or better, 100% of eyes presented with grade 0 glistenings ≤25 MV/mm 2 , and 92.9% of eyes (394/424) had either no PCO or clinically nonsignificant PCO., Conclusions: This study supports the long-term safety and effectiveness of the Clareon IOL. The visual outcomes were excellent and stable over the 3-year study period, PCO rates were very low, and 100% of IOLs had grade 0 glistenings., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

Purpose: To develop a new virtual surgery simulation platform to predict postoperative corneal stiffness (Kc mean ) after laser vision correction (LVC) surgery., Setting: Narayana Nethralaya Eye Hospital and Sankara Nethralaya, India; Humanitas Clinical and Research Center, Italy., Design: Retrospective observational case series., Methods: 529 eyes from 529 patients from 3 eye centers and 10 post-small-incision lenticule extraction (SMILE) ectasia eyes were included. The software (called AcuSimX) derived the anisotropic, fibril, and extracellular matrix biomechanical properties (using finite element calculation) of the cornea using the preoperative Corvis-ST, Pentacam measurement, and inverse finite element method assuming published healthy collagen fibril orientations. Then, the software-computed postoperative Kc mean was adjusted with an artificial intelligence (AI) model (Orange AI) for measurement uncertainties. A decision tree was developed to classify ectasia from normal eyes using the software-computed and preoperative parameters., Results: In the training cohort (n = 371 eyes from 371 patients), the mean absolute error and intraclass correlation coefficient were 6.24 N/m and 0.84 (95% CI, 0.80-0.87), respectively. Similarly, in the test cohort (n = 158 eyes from 158 patients), these were 6.47 N/m and 0.84 (0.78-0.89), respectively. In the 10 ectasia eyes, the measured in vivo (74.01 [70.01-78.01]) and software-computed (74.1 [69.03-79.17]) Kc mean were not statistically different ( P = .96). Although no statistically significant differences in these values were observed between the stable and ectasia groups ( P ≥ .14), the decision tree classification had an area under the receiver operating characteristic curve of 1.0., Conclusions: The new software provided an easy-to-use virtual surgery simulation platform for post-LVC corneal stiffness prediction by clinicians and was assessed in post-SMILE ectasia eyes. Further assessments with ectasia after surgeries are required., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Background: Keratoconus is a degenerative disorder of the cornea leading to a protrusion and thinning with loss of visual acuity. The only treatment to halt the progression is corneal crosslinking (CXL), which uses riboflavin and UV-A light to stiffen the cornea. Recent ultra-structural examinations show that the disease is regional and does not affect the entire cornea. Treating only the affected zone with CXL could be as good as the standard CXL, that treats the entire cornea., Methods: We set up a multicentre non-inferiority randomized controlled clinical trial comparing standard CXL (sCXL) and customized CXL (cCXL). Patients between 16 and 45 years old with progressive keratoconus were included. Progression is based on one or more of the following changes within 12 months: 1 dioptre (D) increase in keratometry (Kmax, K1, K2); or 10% decrease of corneal thickness; or 1 D increase in myopia or refractive astigmatism, requiring corneal crosslinking., Discussion: The goal of this study is to evaluate whether the effectiveness of cCXL is non-inferior to sCXL in terms of flattening of the cornea and halting keratoconus progression. Treating only the affected zone could be beneficial for minimalizing the risk of damaging surrounding tissues and faster wound healing. Recent non-randomized studies suggest that a customized crosslinking protocol based on the tomography of the patient's cornea may stop the progression of keratoconus and result in flattening of the cornea., Trial Registration: This study was prospectively registered at ClinicalTrials.gov on August 31 st , 2020, the identifier of the study is NCT04532788., (© 2023. The Author(s).)

Purpose: To evaluate the cost-effectiveness of Descemet Membrane Endothelial Keratoplasy (DMEK) versus Ultrathin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK)., Methods: A cost-effectiveness analysis using data from a multicenter randomized clinical trial was performed. The time horizon was 12 months postoperatively. Patients with Fuchs' endothelial dystrophy were randomized to DMEK (n = 29) or UT-DSAEK (n = 24). Relevant resources from healthcare and societal perspectives were included in the cost analysis. Quality-Adjusted Life Years (QALYs) were determined using the Health Utilities Index Mark 3 (HUI3) and the EuroQol EQ-5D-5L questionnaires. The main outcome was the incremental cost-effectiveness ratio (ICER; incremental societal costs per QALY)., Results: Societal costs averaged €8851 (US$11 406) for DMEK and €8320 (US$10 722) for UT-DSAEK. Higher costs in the DMEK group were mainly caused by higher rebubbling and regraft rates (21% and 7%, vs. 4% and 0% in the UT-DSAEK group). HUI3 QALYs were 0.70 (DMEK) and 0.79 (UT-DSAEK). EQ-5D-5L QALYs were 0.83 (DMEK) and 0.86 (UT-DSAEK). The ICER indicated DMEK was dominated by UT-DSAEK in both analyses. The cost-effectiveness probability for DMEK ranged from 21% to 5% (HUI3 QALYs) and 27%-14% (EQ-5D-5L QALYs), assuming the maximum acceptable ICER ranged from €2500 to €80.000 (US$3222-US$103 093) per QALY., Conclusion: The base case cost-effectiveness analysis favoured UT-DSAEK over DMEK, as costs of DMEK were higher while QALYs were lower. Further studies are required to assess long-term rebubbling and regraft rates and graft survival., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The purpose of this study was to identify and analyze the clinical and ocular surface risk factors influencing the progression of keratoconus (KC) using an artificial intelligence (AI) model., Methods: This was a prospective analysis in which 450 KC patients were included. We used the random forest (RF) classifier model from our previous study (which evaluated longitudinal changes in tomographic parameters to predict "progression" and "no progression") to classify these patients. Clinical and ocular surface risk factors were determined through a questionnaire, which included presence of eye rubbing, duration of indoor activity, usage of lubricants and immunomodulator topical medications, duration of computer use, hormonal disturbances, use of hand sanitizers, immunoglobulin E (IgE), and vitamins D and B12 from blood investigations. An AI model was then built to assess whether these risk factors were linked to the future progression versus no progression of KC. The area under the curve (AUC) and other metrics were evaluated., Results: The tomographic AI model classified 322 eyes as progression and 128 eyes as no progression. Also, 76% of the cases that were classified as progression (from tomographic changes) were correctly predicted as progression and 67% of cases that were classified as no progression were predicted as no progression based on clinical risk factors at the first visit. IgE had the highest information gain, followed by presence of systemic allergies, vitamin D, and eye rubbing. The clinical risk factors AI model achieved an AUC of 0.812., Conclusion: This study demonstrated the importance of using AI for risk stratification and profiling of patients based on clinical risk factors, which could impact the progression in KC eyes and help manage them better., Competing Interests: None

Dry eye disease (DED) is a multifactorial chronic ocular surface inflammatory condition. Disease severity has been directly related to the immuno-inflammatory status of the ocular surface. Any perturbation in the orchestrated functional harmony between the ocular surface structural cells and immune cells, both resident and trafficking ones, can adversely affect ocular surface health. The diversity and contribution of ocular surface immune cells in DED have been of interest for over a couple of decades. As is true with any mucosal tissue, the ocular surface harbors a variety of immune cells of the innate-adaptive continuum and some of which are altered in DED. The current review curates and organizes the knowledge related to the ocular surface immune cell diversity in DED. Ten different major immune cell types and 21 immune cell subsets have been studied in the context of DED in human subjects and in animal models. The most pertinent observations are increased ocular surface proportions of neutrophils, dendritic cells, macrophages, and T cell subsets (CD4+; CD8+; Th17) along with a decrease in T regulatory cells. Some of these cells have demonstrated disease-causal association with ocular surface health parameters such as OSDI score, Schirmer's test-1, tear break-up time, and corneal staining. The review also summarizes various interventional strategies studied to modulate specific immune cell subsets and reduce DED severity. Further advancements would enable the use of ocular surface immune cell diversity, in patient stratification, i.e. DED-immunotypes, disease monitoring, and selective targeting to resolve the morbidity related to DED., Competing Interests: None

Purpose: Dry eye disease (DED) is characterized by altered ocular surface proinflammatory and antiinflammatory factors. Interferons (IFNs) are a class of pleiotropic cytokines well known for their antimicrobial, inflammatory, and immunomodulatory roles. Hence, this study investigates the ocular surface expression of different types of IFNs in patients with DED., Methods: The cross-sectional, observational study included patients with DED and normal subjects. Conjunctival impression cytology (CIC) samples were obtained from the study subjects (controls, n = 7; DED, n = 8). The mRNA expression levels of type 1 IFN (IFNα, IFNβ), type 2 IFN (IFNγ), and type 3 IFN (IFNλ1, IFNλ2, IFNλ3) were measured by quantitative PCR (polymerase chain reaction) in CIC samples. IFNα and IFNγ expression under hyperosmotic stress was also studied in human corneal epithelial cells (HCECs) in vitro., Results: The mRNA expression levels of IFNα and IFNβ were significantly lower and that of IFNγ was significantly higher in DED patients compared to healthy controls. The mRNA levels of IFNα, IFNβ, and IFNλ were significantly lower compared to IFNγ in DED patients. An inverse association between tonicity-responsive enhancer-binding protein (TonEBP; hyperosmotic stress maker) and IFNα or IFNβ expression and a positive association between TonEBP and IFNγ expression was observed in CIC samples. The expression of IFNα was lower than IFNγ in HCECs undergoing hyperosmotic stress compared to HCECs without the stress., Conclusion: The presence of an imbalance between type 1 and type 2 IFNs in DED patients suggests newer pathogenic processes in DED, plausible ocular surface infection susceptibility in DED patients, and potential therapeutic targets in the management of DED., Competing Interests: None

In a survey of ESCRS member cataract surgeons, 92% felt that operating room waste is excessive and should be reduced; 99% were concerned about global warming and climate change. Most respondents cited restrictions on reuse by manufacturers and regulatory bodies as major drivers of this waste. There was a strong desire to have more reusable options for instruments, devices, and supplies. In comparable percentages with an earlier survey of North American cataract surgeons using the identical questionnaire, there was a strong willingness to reuse many surgical supplies, as well as topical and intraocular medications. This was true even though ESCRS members were much more likely to practice in hospitals (68% vs 35%). The similarities of these results to the North American survey suggest that these attitudes toward sustainability are in fact global and universal. The strong concordance between the 2 surveys suggests that global collaboration is both possible and necessary., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Tear fluid forms a potential source for biomarker identification, and can be minimal invasively collected via Schirmer strips. The lack of knowledge on the processing of Schirmer strips however complicates the analysis and between-study comparisons. We studied two different pre-processing methods, specifically the use of punches of the strip versus elution of the strip in a buffer. Tear fluid filled Schirmer strips were collected from 5 healthy participants, and divided into two halves over the length of the strip. In either part, punches or eluates were obtained from 4 different locations, from the first part touching the eye (head) to the end, to assess the protein distribution along the strips. The levels of 92 inflammatory proteins were measured in the punches/eluates using proximity extension assays. The punch method yielded higher protein detectability compared to the elution method (76% vs 66%; p ≤ 0.001). Protein expression level was found to be slightly higher in the head of the strip, however, 3 out of 5 punches from the head failed quality control. Protein expression levels over the remaining parts of the strips were similar. Our study showed beneficial use of punches of any part of the strip except the head in future biomarker research., (© 2023. The Author(s).)

Purpose: To create a predictive model using artificial intelligence (AI) and assess if available data from patients' registration records can help in predicting definitive endpoints such as the probability of patients signing up for refractive surgery., Methods: This was a retrospective analysis. Electronic health records data of 423 patients presenting to the refractive surgery department were incorporated into models using multivariable logistic regression, decision trees classifier, and random forest (RF). Mean area under the receiver operating characteristic curve (ROC-AUC), sensitivity (Se), specificity (Sp), classification accuracy, precision, recall, and F1-score were calculated for each model to evaluate performance., Results: The RF classifier provided the best output among the various models, and the top variables identified in this study by the RF classifier excluding income were insurance, time spent in the clinic, age, occupation, residence, source of referral, and so on. About 93% of the cases that did undergo refractive surgery were correctly predicted as having undergone refractive surgery. The AI model achieved an ROC-AUC of 0.945 with an Se of 88% and Sp of 92.5%., Conclusion: This study demonstrated the importance of stratification and identifying various factors using an AI model which could impact patients' decisions while selecting a refractive surgery. Eye centers can build specialized prediction profiles across disease categories and may allow for the identification of prospective obstacles in the patient's decision-making process, as well as strategies for dealing with them., Competing Interests: None

Purpose: To compare the prediction accuracy of the Barrett True-K for keratoconus with standard formulas (SRK/T, Barrett Universal II, and Kane) and the Kane keratoconus formula., Setting: Shaare Zedek Medical Center, Jerusalem, Israel, and University Eye Clinic, Maastricht, the Netherlands., Design: Multicenter retrospective case series., Methods: Eyes with stable keratoconus undergoing cataract surgery were included. The predicted refractions were calculated for SRK/T, Barrett Universal II, Barrett True-K for keratoconus (predicted and measured), Kane, and Kane adjusted for keratoconus formulas. Primary outcomes were prediction error (PE), absolute error (AE), and percentage of eyes with PE ±0.25 diopters (D), ±0.50 D, and ±1.00 D. Subgroup analyses were performed based on the severity of the keratoconus., Results: 57 eyes were included in the study. The PE was not significantly different from zero for SRK/T, Barrett True-K (predicted and measured), and Kane keratoconus formulas (range 0.09 to 0.22 D, P > .05). The AE of Barrett True-K predicted (median 0.14 D) and Barrett True-K measured (median 0.10 D) were significantly lower from Barrett Universal II (median 0.47 D) and Kane (median 0.50 D), P < .001., Conclusions: The Barrett True-K formulas for keratoconus had higher prediction accuracy as compared with new generation formulas and a similar prediction accuracy as compared with the Kane keratoconus formula., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

A 27-year-old woman who wants to get rid of contact lenses and spectacles was seen at our clinic. She had strabismus surgery as a child and was patched for the right eye but now shows mild nondisturbing exophoria. Infrequently, she likes to box in the sports school. Her corrected distance visual acuity at presentation in the right eye was 20/16 with -3.75 -0.75 × 50 and in the left eye 20/16 with -3.75 -1.25 × 142. Her cycloplegic refraction in the right eye was -3.75 -0.75 × 44 and in the left eye was -3.25 -1.25 × 147. The left eye is the dominant eye. The tear break-up time was 8 seconds in both eyes, and the Schirmer tear test was 7 to 10 mm in right and left eyes, respectively. Pupil sizes under mesopic conditions were 6.62 mm and 6.68 mm. The anterior chamber depth (ACD) (measured from the epithelium) in the right eye was 3.89 mm and in the left eye was 3.87 mm. The corneal thickness was 503 μm and 493 μm of the right and left eye, respectively. Corneal endothelial cell density was on average 2700 cells/mm2 for both eyes. Slitlamp biomicroscopy showed clear corneas and a normal flat iris configuration. Supplemental Figures 1 to 4 (available at http://links.lww.com/JRS/A818, http://links.lww.com/JRS/A819, http://links.lww.com/JRS/A820, and http://links.lww.com/JRS/A821) show the corneal topography and Belin-Ambrósio deviation (BAD) maps at presentation of the right eye and left eye, respectively. Would you consider this patient a candidate for corneal refractive surgery (eg, laser-assisted subepithelial keratectomy, laser in situ keratomileusis [LASIK], or small-incision lenticule extraction [SMILE] procedure)? Has your opinion changed given the recent opinion of the U.S. Food and Drug Administration (FDA) regarding LASIK?1 The patient herself is slightly favoring an implantation of a phakic intraocular lens (pIOL), as she prefers something reversible. Would you implant a pIOL, and which type of IOL, for this level of myopia? What is your diagnosis or are additional diagnostic methodologies needed to establish a diagnosis? What is your treatment advice for this patient? REFERENCES 1. U.S. Food and Drug Administration, HHS. Laser-assisted in situ keratomileusis (LASIK) lasers-patient labeling recommendations; draft guidance for industry and food and drug administration staff; availability. July 28, 2022, Federal Register; 87 FR 45334. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/laser-assisted-situ-keratomileusis-lasik-lasers-patient-labeling-recommendations Accessed January 25, 2023., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: To validate the Easee web-based tool for the assessment of visual acuity in patients who underwent cataract surgery., Setting: University Eye Clinic Maastricht, Maastricht, the Netherlands., Design: Prospective method comparison study., Methods: Subjects aged between 18 and 69 years who underwent cataract surgery on 1 or both eyes at the Maastricht University Medical Center+ were eligible to participate in this study. The uncorrected (UDVA) and corrected distance visual acuity (CDVA) assessments were performed using the web-based tool (index test) and conventional ETDRS and Snellen charts (reference tests). The outcomes of the different tests were expressed in logMAR, and a difference of <0.15 logMAR was considered clinically acceptable., Results: 46 subjects with 75 operated eyes were included in this study. The difference of the UDVA between the web-based tool and ETDRS or Snellen was -0.05 ± 0.10 logMAR ( P < .001 [0.15; -0.26]) and -0.04 ± 0.15 logMAR ( P = .018 [0.24; -0.33]), respectively. For the CDVA, these differences were -0.04 ± 0.08 logMAR ( P < .001 [0.13; -0.21]) and -0.07 ± 0.10 logMAR ( P < .001 [0.13; -0.27]), respectively. The Pearson correlation coefficients between the web-based tool and ETDRS were maximally 0.94 and compared with Snellen 0.92. In total, 73% to 88% of the visual acuity measurement differences were within 0.15 logMAR., Conclusions: The web-based tool was validated for the assessment of visual acuity in patients who underwent cataract surgery and showed clinically acceptable outcomes in up to 88% of patients. Most of the participants had a positive attitude toward the web-based tool, which requires basic digital skills., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

Purpose: The purpose of this study was to investigate the predictive value of pachymetry mapping 1 day after Descemet membrane endothelial keratoplasty (DMEK) as a biomarker for early graft detachment., Methods: This was a post hoc analysis of 65 pseudophakic subjects with Fuchs endothelial dystrophy who underwent DMEK surgery between December 2018 and April 2021 as part of the Advanced Visualization In Corneal Surgery Evaluation international multicenter randomized controlled trial. One eye per patient was included. Preoperatively and 1 day postoperatively, patients underwent anterior segment optical coherence tomography imaging. Using a grid consisting of 25 zones (ie, pachymetry map), corneal thickness and presence of a graft detachment were mapped for each patient. Detachments of any size were considered, regardless of subsequent clinical interventions. Missing data were imputed and subsequently divided into a training and test set. Two prediction methods were evaluated: one model based on absolute corneal thickness and a regression model., Results: A total of 65 eyes were included for analysis of which 33 developed any form of graft detachment. Preoperatively, no significant differences were observed between the groups ( P = 0.221). Corneal thickness in the corneal zones with a detached graft was significantly increased compared with corneal zones with an attached graft ( P < 0.001). The regression prediction model had an area under the curve of 0.87 (sensitivity: 0.79 and specificity: 0.75), whereas the absolute thickness cutoff model only reached 0.65., Conclusions: Pachymetry mapping 1 day after DMEK was predictive for early graft detachment, and the prediction model had a good to excellent performance. This aids in identifying patients at risk for graft detachment and subsequent tailored postoperative care., Competing Interests: The authors have no funding or conflicts of interest to disclose. The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cataract surgery has become one of the most performed surgical procedures worldwide. Postoperative management consists of routine clinical examinations to assess post-operative visual function and detect possible adverse events. Due to the low incidence of complications, the majority of clinic visits after cataract surgery are uneventful. Nonetheless, valuable time and hospital resources are consumed. We hypothesize that remote post-operative follow-up involving teleconsultations and self-assessments of visual function and health status, could be a valid alternative to face-to-face clinical examinations in selected patient groups. The practice of remote follow-up after cataract surgery has not yet been evaluated. The aim of this study is to investigate the validity, safety and cost-effectiveness of remote cataract surgery follow-up, and to report on the patients' experiences with remotely self-assessing visual function., Methods: This study is a multicenter, open-label, randomized controlled trial. Patients planned for cataract surgery on both eyes, without ocular comorbidities, are eligible for participation. Participants will be allocated (1:1) into one of the two study groups: 'telemonitoring' or 'usual care'. Participants in the 'telemonitoring' group will perform in-home assessments after cataract surgery (remote web-based eye exams and digital questionnaires on their own devices). Participants in the 'usual care' group will have regular post-operative consultations, according to the study site's regular practice. Outcome measures include accuracy of the web-based eye exam for assessing visual acuity and refraction, patient-reported outcome measures (visual function and quality of life), adverse events, and cost aspects., Discussion: Investigating remote follow-up after cataract surgery fits the current trends of digitization of health care. We believe that remote self-care can be a promising avenue to comply with the increasing demands of cataract care. This randomized controlled trial provides scientific evidence on this unmet need and delivers the desired insights on (cost)effectiveness of remote follow-up after cataract surgery., Trial Registration: ClinicalTrials.gov: NCT04809402. Date of registration: March 22, 2021., (© 2023. The Author(s).)

Tear fluid is emerging as a source of non-invasive biomarkers, both for ocular and systemic conditions. Accurate quantification of tear proteins can be improved by standardizing methods to collect and process tear fluid. The aim of this study was to determine sample handling factors that may influence the tear protein biomarker profile. Tear fluid was collected using Schirmer's strips. Tear proteins were extracted by elution through centrifugation. Total protein content was determined using the bicinchoninic acid assay. Key concepts that apply to the entire sample processing cycle are tear sampling, tear storage, protein extraction and data normalization. Differences in wetting or migration length were observed between Schirmer's strips from different manufacturers, and between protein-free and protein-rich solutions. One unit of migration length (mm) did not correspond to one unit of volume (µL). A positive correlation (r = 0.6671, p < 0.0001) was observed between migration length and total tear protein content. The most beneficial storage conditions were strips that were not stored (+ 21.8%), or underwent 'wet' storage (+ 11.1%). Protein recovery was the highest in 400 µL extraction buffer and independent of protein molecular weight. This study helps to explain inter- and intra-variability that is often seen with tear biomarker research. This information is critical to ensure accuracy of test results, as tear biomarkers will be used for patient management and in clinical trials in the near future. This study also highlights the need for standardization of Schirmer's strip manufacturing, tear fluid processing and analyte concentration normalization., (© 2023. The Author(s).)

Objective: To evaluate if an intraoperative-OCT (iOCT) optimized surgical protocol without prolonged overpressure is non-inferior to a standard protocol during Descemet membrane endothelial keratoplasty (DMEK)., Methods: Sixty-five pseudophakic eyes of 65 patients with Fuchs endothelial dystrophy scheduled for routine DMEK were recruited in this prospective non-inferiority international multicenter randomized control trial. Subjects were randomized to the control arm (n=33) without iOCT-use and raising the intraocular pressure above normal physiological limits for 8 minutes (i.e., overpressure) or the intervention arm (n=32) with OCT-guidance to assess graft orientation and adherence, while refraining from prolonged overpressure. The primary outcome was the incidence of postoperative surgery-related adverse events (AE). The non-inferiority margin was set at a risk difference of 10%. Secondary outcomes included iOCT-aided surgical decision making, surgical times, and endothelial cell density (ECD) corrected distance visual acuity (CDVA) at 6 months follow-up., Results: In the intervention group, 12 subjects developed 13 AEs compared to 13 AEs in 10 subjects in the control group (P=0.644). The risk difference measured -0.32% (95%CI: -10.29 - 9.84). The ECD and CDVA did not differ between the two groups 3 and 6 months postoperatively (P=>0.05). Surgeons reported that iOCT aided surgical decision-making in 40% of cases. Surgery and graft unfolding time were, respectively, 13% and 27% shorter in the iOCT-group., Conclusions: iOCT-guided DMEK surgery with refraining from prolonged over-pressuring was non-inferior compared to conventional treatment. Surgery times were reduced considerably and iOCT aided surgical decision-making in 40% of cases. Refraining from prolonged overpressure did not affect postoperative ECD or CDVA., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03763721 (NCT03763721)., Competing Interests: RW is consultant for Carl Zeiss Meditec AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Muijzer, Delbeke, Dickman, Nuijts, Noordmans, Imhof and Wisse.)

Purpose of Review: The aim of this study was to present an overview of recent publications and opinions in the field of same-day bilateral cataract surgery., Recent Findings: A Cochrane review was published comparing immediate sequential bilateral cataract surgery (ISBCS) and delayed sequential bilateral cataract surgery (DSBCS) with regard to safety outcomes, costs and cost-effectiveness. In addition, several large database studies provided more information on incidences of rare complications such as unilateral and bilateral endophthalmitis rates., Summary: Recently available evidence showed that ISBCS is an effective and cost-effective alternative to DSBCS. Nonetheless, additional (randomized) registry studies, randomized controlled trials and cost-effectiveness studies are needed to evaluate bilateral endophthalmitis rates, refractive outcomes and cost-effectiveness of ISBCS compared with DSBCS., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To assess phase retardation and corneal sublayer thickness repeatability using ultrahigh-resolution polarization-sensitive optical coherence tomography (PS-OCT)., Setting: Narayana Nethralaya Eye Hospital, Bangalore., Design: Observational., Methods: In this study, all eyes were imaged using a custom-built ultrahigh-resolution PS-OCT and high-resolution hybrid OCT (MS-39). The repeatability of phase retardation en face maps and corneal sublayer thickness profiles was evaluated. The reflectivity and phase retardation were calculated from the 2 orthogonal polarization channels to generate en face maps of phase retardation and corneal sublayer thicknesses. 3 consecutive measurements of all participants were acquired for each eye. For each measurement, the participant was asked to sit back and was realigned again. The repeatability was assessed using the intraclass correlation coefficient (ICC)., Results: The study included 20 healthy eyes of 20 participants. The phase retardation en face maps showed preferential arrangement of collagen fibrils with least retardation in the apex and maximum retardation in the periphery. The phase retardation showed excellent repeatability (ICC >0.95) in all zones. The Bowman layer and stromal layer thicknesses were measured with excellent repeatability (ICC >0.93 and >0.99, respectively). Significant differences ( P < .05) in stromal layer thickness were observed between MS-39 and PS-OCT. The repeatability of epithelial thickness measurements was better with PS-OCT than MS-39., Conclusions: The combinational assessment of corneal birefringence and sublayer thicknesses shows the advanced potential of ultrahigh-resolution PS-OCT in routine clinical practice over current OCT devices., (Copyright © 2022 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)