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Intraocular Lens Power Calculation—Comparing Big Data Approaches to Established Formulas

Purpose To evaluate the predictive performance of traditional intraocular lens (IOL) power calculation formulas (e.g., SRK/T, Haigis, Hoffer Q, and Holladay I) compared to advanced regression models, including classical linear models, regression splines, and random forest regression, in predicting postoperative refraction following cataract surgery. Design Retrospective, comparative analysis of IOL power calculations. Subjects The study included 886 eyes from 631 patients who underwent cataract surgery with monofocal aspherical IOL implantation. Methods Biometric measurements were obtained using optical biometry (IOLMaster 700), and postoperative refraction was assessed at least 4 weeks after surgery. Formula constants for 5 IOL formulas (SRK/T, Haigis, Hoffer Q, Holladay I and Castrop V1) were optimized using root mean squared error (RMSE). Regression models (classical linear model, regression splines, and random forest regression) were trained on 4 datasets categorized by axial length (AL); normal, short, long, and random. Model performance was assessed using mean absolute error (MAE), RMSE, and prediction error variance, for both in-sample and out-of-sample predictions. Main Outcome Measures The primary parameters measured were MAE, RMSE, and prediction error variance. Results Regression models outperformed traditional IOL formulas in in-sample prediction error. Overall, linear regression models performed similarly to traditional formulas with respect to out-of-sample prediction error. The lowest out-of-sample prediction error (MAE = 0.279, RMSE = 0.359) was achieved with a model where effects of some covariates (R2, AL, CCT) were modelled as nonlinear via regression splines. This model outperformed all traditional formulas, and the Castrop formula, which had the lowest errors among the formulas (MAE = 0.284, RMSE = 0.359). Random forest regression showed strong in-sample performance but poor out-of-sample generalizability due to overfitting. Conclusions Regression models which allow for nonlinear effects, e.g. based on regression splines, provide a promising alternative to traditional IOL formulas for predicting postoperative refraction. Linear regression and random forest regression models can reduce in-sample error, however, their clinical utility is currently limited by out-of-sample performance. Future work should focus on improving generalizability and integrating machine learning models into clinical practice to enhance refractive outcomes, especially for eyes with atypical anatomy

Role of fatty acid transporters in epidermis: Implications for health and disease

Skin epidermis is an active site of lipid synthesis. The intercellular lipids of human stratum corneum (SC) are unique in composition and quite different from the lipids found in most biological membranes. The three major lipids in the SC are free fatty acids, cholesterol and ceramides. Fatty acids can be synthesized by keratinocytes de novo and, in addition, need to be taken up from the circulation. The latter process has been shown to be protein mediated, and several fatty acid transporters are expressed in skin. Recent studies of transgenic and knockout animal models for fatty acid transporters and the identification of fatty acid transport protein 4 (FATP4 or SLC27A4) mutations as causative for Ichthyosis Prematurity Syndrome highlight the vital roles of fatty acid transport and metabolism in skin homeostasis. This review provides an overview of our current understanding of the role of fatty acids and their transporters in cutaneous biology, including their involvement in epidermal barrier generation and skin inflammation

An Inverse Relationship Between Ceramide Synthesis and Clinical Severity in Patients with Psoriasis

Ceramides play major roles in maintaining the epidermal barrier. It has been sus-pected that the depletion of ceramides, associated with disrupted barrier function in the epidermis, leads to the clinical manifestation of dryness and inflammation seen in patients with psoriasis. The aim of the present study was to determine the relation-ship between the level of ceramide synthesis in the epidermis and the clinical severity in patients with psoriasis. Samples from lesional and unlesional epidermis obtained from psoriasis patients were incubated with [14C]serine, an initiator of ceramide syn-thesis. otal ceramide was fractionated using high performance thin layer chromato-graphy, and the radioactivity was measured. The clinical severity of psoriasis was graded according to the psoriasis area and severity index scoring system. The level of ceramide synthesis in the lesional epidermis of patients was significantly lower than that in the unlesional epidermis and bore a negative correlation with the clinical severity of psoriasis. The present results suggest that the decreased level of ceramide synthesis in the epidermis contributes to the clinical severity of psoriasis

Non-invasive Approaches for the Diagnosis of Autoimmune/Autoinflammatory Skin Diseases—A Focus on Psoriasis and Lupus erythematosus

The traditional diagnostic gold standard for inflammatory skin lesions of unclear etiology is dermato-histopathology. As this approach requires an invasive skin biopsy, biopsy processing and analysis by specialized histologists, it is a resource intensive approach requiring trained healthcare professionals. In many health care settings access to this diagnostic approach can be difficult and outside emergency cases will usually take several weeks. This scenario leads to delayed or inappropriate treatment given to patients. With dramatically increased sensitivity of a range of analysis systems including mass spectrometry, high sensitivity, multiplex ELISA based systems and PCR approaches we are now able to “measure” samples with unprecedented sensitivity and accuracy. Other important developments include the long-term monitoring of parameters using microneedle approaches and the improvement in imaging systems such as optical coherence tomography. In this review we will focus on recent achievements regarding measurements from non-invasive sampling, in particular from plucked hair and skin tape-strips which seem well suited for the diagnosis of lupus erythematosus and psoriatic inflammation, respectively. While these approaches will not replace clinical observation—they can contribute to improved subgroup diagnosis, stratified therapeutic approaches and have great potential for providing molecular and mechanistic insight in to inflammatory skin diseases.With dramatically increased sensitivity of a range of analysis systems including mass spectrometry, high sensitivity, multiplex ELISA based systems and PCR approaches we are now able to “measure” samples with unprecedented sensitivity and accuracy. Other important developments include the long-term monitoring of parameters using microneedle approaches and the improvement in imaging systems such as optical coherence tomography. In this review we will focus on recent achievements regarding measurements from non-invasive sampling, in particular from plucked hair and skin tape-strips which seem well suited for the diagnosis of lupus erythematosus and psoriatic inflammation, respectively. While these approaches will not replace clinical observation – they can contribute to improved subgroup diagnosis, stratified therapeutic approaches and have great potential for providing molecular and mechanistic insight in to inflammatory skin disease