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Background: In recent years, some lens manufacturers have committed to providing lens shape data for some of their lens models. The purpose of this study is to present a strategy for prediction of intraocular lens power and residual refraction based on a pseudophakic model eye containing 5 refractive surfaces and to show its applicability using worked examples. Methods: A pseudophakic model eye with a thin spectacle correction, a thick cornea (radius of curvatures for both surfaces and central thickness) and a thick IOL (either radius of curvatures RLa and RLp for front and back surface or equivalent power PL and Coddington factor CL; and either central thickness LT or edge thickness and optic diameter) was set up. Calculations were performed based on linear Gaussian optics (vergence formulae). Formulae were provided to derive the lens power/shape and the residual equivalent spectacle refraction SEQ. From the lens shape the location of the haptic plane HP, the image sided principal plane of the lens HL, and the ocular magnification OM were extracted. Results: The calculation of a thick intraocular lens and the prediction of residual refraction is presented with reference to 3 working examples: A) lens varied in PL and shifted with its haptic plane keeping the CL constant, B) lens varied in CL and shifted with its haptic plane keeping PL constant, and C) CL and PL of the lens varied keeping its haptic plane position in the eye constant. For each combination of parameters (PL, CL, or haptic plane shift) the parameters influencing SEQ, OM and HL-HP were analysed. Conclusion: Some modern optical biometers currently on the market provide the radii of curvature of both corneal surface and all relevant distances in the eye. With additional data on the lens shape, it would be possible to improve lens power calculations by switching from thin to thick lens models for the cornea and for the lens. This would overcome one of the major drawbacks of current lens power calculation methods.

Purpose: To implement a fully data driven strategy for identifying outliers in clinical datasets used for formula constant optimisation, in order to achieve proper formula predicted refraction after cataract surgery, and to assess the capabilities of this outlier detection method. Methods: 2 clinical datasets (DS1/DS2: N = 888/403) of eyes treated with a monofocal aspherical intraocular lens (Hoya XY1/Johnson&Johnson Vision Z9003) containing preoperative biometric data, power of the lens implant and postoperative spherical equivalent (SEQ) were transferred to us for formula constant optimisation. Original datasets were used to generate baseline formula constants. A random forest quantile regression algorithm was set up using bootstrap resampling with replacement. Quantile regression trees were grown and the 25% and 75% quantile, and the interquartile range were extracted from SEQ and formula predicted refraction REF for the SRKT, Haigis and Castrop formulae. Fences were defined from the quantiles and data points outside the fences were marked and removed as outliers before recalculating the formula constants. Results: NB = 1000 bootstrap samples were derived from both datasets, and random forest quantile regression trees were grown to model SEQ versus REF and to estimate the median and 25% and 75% quantiles. The fence boundaries were defined as being from 25% quantile - 1.5·IQR to 75% quantile + 1.5·IQR, with data points outside the fence being marked as outliers. In total, for DS1 and DS2, 25/27/32 and 4/5/4 data points were identified as outliers for the SRKT/Haigis/Castrop formulae respectively. The respective root mean squared formula prediction errors for the three formulae were slightly reduced from: 0.4370 dpt;0.4449 dpt/0.3625 dpt;0.4056 dpt/and 0.3376 dpt;0.3532 dpt to: 0.4271 dpt;0.4348 dpt/0.3528 dpt;0.3952 dpt/0.3277 dpt;0.3432 dpt for DS1;DS2. Conclusion: We were able to prove that with random forest quantile regression trees a fully data driven outlier identification strategy acting in the response space is achievable. In a real life scenario this strategy has to be complemented by an outlier identification method acting in the parameter space for a proper qualification of datasets prior to formula constant optimisation.

Abstract Objectives This retrospective analysis evaluates the treatment success of “Defocus Incorporated Multiple Segments” (DIMS) spectacle lenses in a real-life clinical setting in Germany. Materials and methods Axial length (AL) and objective refraction of 166 eyes treated with DIMS at baseline and 12-month follow-up were analyzed. Annual AL growth rate within the range of physiological growth rate was considered a successful treatment. Myopia progression of ≥ -0.5 D/yr accounted as treatment success. Differences in percentages of treatment success of subgroups depending on baseline AL and age against treatment success of the total population were investigated. Results Considering all eyes, treatment success regarding AL growth and myopia progression was achieved in 46% and 65%, respectively. Male eyes with moderate AL showed treatment success in a higher proportion (73%, p

PurposeRose Bengal Photodynamic Therapy (RB-PDT) offers dual therapeutic benefits by enhancing corneal stiffness and providing antibacterial activity, presenting significant potential for patients with keratoconus complicated by keratitis. Our purpose was to assess the effect of rose bengal photodynamic therapy (RB-PDT) on the expression of pro-inflammatory cytokines and chemokines, as well as on extracellular matrix (ECM)-related molecules, in lipopolysaccharide (LPS)-induced inflammation of keratoconus human corneal fibroblasts (KC-HCFs). Additionally, the involvement of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways which are downstream of the Toll-like receptor 4 (TLR4) pathway were examined.MethodsKC-HCFs were stimulated with varying concentrations of LPS (0-10 μg/ml), which was followed by RB-PDT. The expression levels of interleukin-1β (IL-1β), IL-6, IL-8, interferon alpha 2 (IFNA2), IFNB1, intercellular adhesion molecule 1 (ICAM-1), chemokine (C-C motif) ligand 4 (CCL-4), collagen I, collagen V, lysyl oxidase (LOX), transforming growth factor β 1(TGF-β1) were measured using qPCR, ELISA, or western blot. The activation of the NF-κB and MAPK pathways was assessed using qPCR and western blot.ResultsIn LPS-induced inflammation of KC-HCFs, the expression of IL-6 was further amplified by the treatment with RB-PDT (p = 0.001). However, the activation of the MAPK and NF-κB pathways did not increase following RB-PDT. Additionally, RB-PDT reduced the transcription of collagen I and collagen V (p≤0.03), while the transcription of LOX and TGF-β1 secretion remained unchanged in KC-HCFs exposed to LPS.ConclusionIn LPS-induced inflammation of KC-HCFs treated with RB-PDT, despite the increased expression of pro-inflammatory cytokines, the activation of the TLR4 signaling pathways is lacking. RB-PDT may have no adverse effects on corneal scar formation of keratoconus corneas in the short term.

PurposeTo investigate different measures for corneal astigmatism in the context of reconstructed corneal astigmatism (recCP) as required to correct the pseudophakic eye, and to derive prediction models to map measured corneal astigmatism to recCP.MethodsRetrospective single centre study of 509 eyes of 509 cataract patients with monofocal (MX60P) IOL. Corneal power measured with the IOLMaster 700 keratometry (IOLMK), and Galilei G4 keratometry (GK), total corneal power (TCP2), and Alpin's integrated front (CorT) and total corneal power (CorTTP). Feedforward shallow neural network (NET) and linear regression (REG) prediction models were derived to map the measured C0 and C45 power vector components to the respective recCP components.ResultsBoth the NET and REG models showed superior performance compared to a constant model correcting the centroid error. The mean squared prediction errors for the NET/REG models were: 0.21/0.33 dpt for IOLMK, 0.23/0.36 dpt for GK, 0.24/0.35 for TCP2, 0.23/0.39 dpt for CorT and 0.22/0.36 dpt for CorTTP respectively (training data) and 0.27/0.37 dpt for IOLMK, 0.26/0.37 dpt for GK, 0.38/0.42 dpt for TCP2, 0.35/0.36 dpt for CorT, and 0.44/0.45 dpt for CorTTP respectively on the test data. Crossvalidation with model optimisation on the training (and validation) data and performance check on the test data showed a slight overfitting especially with the NET models.ConclusionsMeasurement modalities for corneal astigmatism do not yield consistent results. On training data the NET models performed systematically better, but on the test data REG showed similar performance to NET with the advantage of easier implementation.

Acquired drug resistance to anticancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified1-4, the underlying molecular mechanisms shaping tumour evolution during treatment are incompletely understood. Genomic profiling of patient tumours has implicated apolipoprotein B messenger RNA editing catalytic polypeptide-like (APOBEC) cytidine deaminases in tumour evolution; however, their role during therapy and the development of acquired drug resistance is undefined. Here we report that lung cancer targeted therapies commonly used in the clinic can induce cytidine deaminase APOBEC3A (A3A), leading to sustained mutagenesis in drug-tolerant cancer cells persisting during therapy. Therapy-induced A3A promotes the formation of double-strand DNA breaks, increasing genomic instability in drug-tolerant persisters. Deletion of A3A reduces APOBEC mutations and structural variations in persister cells and delays the development of drug resistance. APOBEC mutational signatures are enriched in tumours from patients with lung cancer who progressed after extended responses to targeted therapies. This study shows that induction of A3A in response to targeted therapies drives evolution of drug-tolerant persister cells, suggesting that suppression of A3A expression or activity may represent a potential therapeutic strategy in the prevention or delay of acquired resistance to lung cancer targeted therapy.

Purpose: The number of presbyopia-correcting (premium) intraocular lenses (IOLs) is growing steadily as the desire for spectacle independence after cataract surgery increases. The aim of this laboratory study was to evaluate a newly launched hydrophobic, acrylic, polyfocal, refractive intraocular lens with a new optical design and geometry. This polyfocal IOL has three different zones (within the optic) with radially asymmetric design. Methods: We performed optical bench tests to calculate the optical characteristics of the sample. The optical performance and quality of IOLs based on ISO 11979-2 and 11979-9 requirements were analyzed with the NIMO TR0815 (Lambda-X). In addition, optical quality metrics were evaluated with the IOLA MFD device (Rotlex). Sphere, Add, modulation transfer function (MTF), the energy distribution between the modes and the MTF along the whole range from far to near were analyzed. Results: The power histogram showed that the tested IOL has the characteristics of a polyfocal IOL with a wide range of optical power between 20.5 and 24.5 diopters. Two distinct peaks were observed, indicating bifocal functionality. In the radial and axial power surface map, all three zones, stated by the company, could be detected. Larger apertures lead to a significant increase in MTF at the far peak, indicating better visual acuity for distant objects under low-light conditions. It was observed that in small aperture sizes, intermediate vision seems to be dominant. The energy distribution remained almost constant with increasing aperture size. Conclusions: This laboratory study was able to confirm the properties of the polyfocal lens stated by the company. Three optical zones could be identified. However, further optical bench tests should be performed to evaluate the new lens under tilted and decentered conditions. Clinical studies have to confirm that the presbyopia-correcting, polyfocal lens can achieve good clinical results with high patient satisfaction without disturbing side effects.