Tracking the evolution of CNS remyelinating lesion in mice with neutral red dye.

Animal models of central nervous system (CNS) demyelination, including toxin-induced focal demyelination and immune-mediated demyelination through experimental autoimmune encephalomyelitis (EAE), have provided valuable insights into the mechanisms of neuroinflammation and CNS remyelination. However, the ability to track changes in transcripts, proteins, and metabolites, as well as cellular populations during the evolution of a focal lesion, has remained challenging. Here, we developed a method to label CNS demyelinating lesions by the intraperitoneal injection of a vital dye, neutral red (NR), into mice before killing. We demonstrate that NR-labeled lesions can be easily identified on the intact spinal cord in both lysolecithin- and EAE-mediated demyelination models. Using fluorescence microscopy, we detected NR in activated macrophages/microglia and astrocytes, but not in oligodendrocytes present in lesions. Importantly, we successfully performed RT-qPCR, Western blot, flow cytometry, and mass spectrometry analysis of precisely dissected NR-labeled lesions at 5, 10, and 20 d postlesion (dpl) and found differential changes in transcripts, proteins, cell populations, and metabolites in lesions over the course of remyelination. Therefore, NR administration is a simple and powerful method to track and analyze the detailed molecular, cellular, and metabolic changes that occur within the lesion microenvironment over time following CNS injury. Furthermore, this method can be used to identify molecular and metabolic pathways that regulate neuroinflammation and remyelination and facilitate the development of therapies to promote repair in demyelinating disorders such as multiple sclerosis.

Correlational Analysis of the Effective Optical Zone with Myopia, Myopic Astigmatism, and Spherical Equivalent in LASIK, PRK, and SMILE.

Purpose: We assess the relationship between preoperative myopic sphere, astigmatism, and spherical equivalent and effective optical zone (EOZ) size, shape, and decentration within individual populations of post-LASIK, PRK, and SMILE patients. Patients and Methods: A retrospective chart review was conducted with 118 LASIK, 144 PRK, and 41 SMILE eyes from 179 total patients that underwent compound myopic ablation. One-year postoperative Pentacam tangential difference maps were used for EOZ data measurements. Correlational analysis between compound myopic measures [sphere, cylinder, manifest refractive spherical equivalent (MRSE)] and EOZ parameters was performed, and differences between groups of myopic sphere and cylinder within each surgery type were assessed. Results: An increase in absolute myopic sphere (and subsequent MRSE) is associated with a smaller EOZ area in SMILE (r=0.454, p=0.003) and a more circular EOZ shape in LASIK (r=0.396, p<0.001) and PRK (r=0.563, p<0.001). An increase in absolute myopic cylinder is associated with an increased EOZ area in all three surgery types [LASIK (r=-0.459, p<0.001), PRK (r=-0.716, p<0.001), SMILE (r=-0.429, p=0.005)] and a more elliptical EOZ in LASIK (r=-0.491, p<0.001) and PRK (r=-0.538, p<0.001). Conclusion: While astigmatism may be correlated to EOZ size within all three refractive surgery types, myopic sphere alone is insufficient to estimate EOZ size differences for procedures with a large blend zone of ablation like LASIK or PRK. Shape is just as important a factor as size to consider when examining corneal EOZ differences; reported correlative findings likely result from inherent differences in surgical technique and abruptness of planned surgical ablation borders.

Changes in Posterior Cornea and Posterior-To-Anterior Curvature Radii Ratio 1 Year After LASIK, PRK, and SMILE Treatment of Myopia.

PURPOSE: The purpose of this study was to compare changes in the posterior curvature and the posterior-anterior radii ratio of the cornea, 1 year postoperatively in laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and small incision lenticule extraction (SMILE). METHODS: This retrospective study was performed at a single surgical center. 199 eyes were included in the study from 119 patients with manifest refraction spherical equivalents from -7.61 to -2.54 D. 67 eyes underwent LASIK, 89 underwent PRK, and 43 underwent SMILE. Both preoperative and 1-year postoperative front and back sagittal keratometry were measured at 4- to 6-mm zones around the corneal vertex. Corneal asphericity (Q-value) was measured at an 8-mm zone around the corneal vertex. RESULTS: The average change in the posterior-anterior radii ratio after LASIK, PRK, and SMILE did not differ between surgery groups at 4 mm (LASIK: -0.075, PRK: -0.073, SMILE: -0.072, P = 0.720), 5 mm (LASIK: -0.072, PRK: -0.068, SMILE: -0.068, P = 0.531), or 6 mm (LASIK: -0.075, PRK: -0.071, SMILE: -0.072, P = 0.456) zones. Anterior Q-value significantly positively increased after all 3 surgeries ( P < 0.001). The posterior Q-value also significantly positively increased after LASIK ( P < 0.001) and SMILE ( P < 0.001), but not after PRK ( P = 0.227). Both anterior and posterior keratometric power decreased significantly after LASIK, PRK, and SMILE for all diameters. CONCLUSIONS: The change in the posterior-anterior radii ratio was not influenced by the type of refractive surgery performed, as indicated by statistically identical preoperative, postoperative, and delta values. In addition, the posterior cornea exhibited paracentral flattening after LASIK, SMILE, and PRK and increased oblateness after LASIK and SMILE.

Comparing Effective Optical Zones After Myopic Ablation Between LASIK, PRK, and SMILE With Correlation to Higher Order Aberrations.

PURPOSE: To explore size, decentration, and eccentricity of effective optical zones (EOZs) in laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and small incision lenticule extraction (SMILE) and correlate them to higher order aberrations (HOAs). METHODS: This was a retrospective chart review of 188 eyes that underwent refractive surgery for compound myopia (61 LASIK, 84 PRK, 43 SMILE). EOZ measurements were determined using 1-year postoperative Pentacam (Oculus Optikgeräte GmbH) tangential difference maps. HOA data were measured using Pentacam wavefront aberration Zernike polynomials. Correlations between EOZs and HOAs were analyzed. RESULTS: The EOZs of LASIK and PRK are smaller than SMILE at 19.54 ± 1.44, 19.39 ± 1.66, and 22.18 ± 2.61 mm2, respectively (P < .001). No difference existed in absolute decentration from corneal vertex (P = .078) or pupil center (P = .131), but horizontal and vertical components differed significantly (P < .001). Smaller EOZ areas were correlated with greater spherical aberration induction (rLASIK = -0.378, rPRK = -0.555, rSMILE = -0.501) and total HOA induction in all groups. Absolute decentration from corneal vertex positively correlated with total HOA (rLASIK = 0.396, rPRK = 0.463, rSMILE = 0.399) and directional vertical coma induction negatively correlated with vertical decentration from the corneal vertex (rLASIK = -0.776, rPRK = -0.665, rSMILE = -0.576) in all groups. CONCLUSIONS: SMILE results in a larger EOZ than LASIK and PRK, and absolute decentration remains comparable regardless of surgical reference center, despite horizontal/vertical differences. Surgical planning to ensure adequate EOZ size and centration may reduce induction of HOAs, including spherical aberrations and vertical coma. [J Refract Surg. 2023;39(11):741-750.].

Exploring Nomograms for Implantable Collamer Lens Size Selection in Myopia: A Literature-based Compilation.

Purpose: To provide a comprehensive guide of all implantable collamer lens (ICL) sizing nomograms and the respective preoperative diagnostic devices that are required. This guide would help clinicians in choosing the appropriate ICL size for myopic patients to optimize postoperative vault height. Methods: A literature search of peer-reviewed journals describing methods and postoperative outcomes of ICL sizing was conducted. Research articles containing ICL nomograms or formulas were identified from this search. Preoperative variables necessary for these nomograms and the required diagnostic devices to measure these parameters such as topography, biometry, or ultrasound biomicroscopy (UBM) were noted. An additional search was conducted to identify artificial intelligence (AI) or machine learning (ML)-derived nomograms. Results: Eighteen ICL sizing nomograms were identified through literature search. Five of these nomograms are available for use and require topography or biometry devices. Of these, four include the manufacturer's, optimized white-to-white (WTW), Kang, Kim, and Rocamora Nomograms. Eight of the 18 nomograms available for use require UBM. Eight of these include the Kojima, Nakamura, KS, ZZ, Dougherty, Parkhurst, Russo, and Reinstein Nomograms. Four of the 18 nomograms are ML-derived including Shen, Rocamora, Russo, and Kang Nomograms. Conclusion: ICL nomograms are a vital tool in helping clinicians select the right ICL size for myopic patients to optimize postoperative vault reducing risk of postoperative complications. Based on available diagnostic devices such as topography, biometry, or UBM clinicians can integrate specific nomograms into practice.

Prediction of Posterior-to-Anterior Corneal Curvature Radii Ratio in Myopic Patients after LASIK, SMILE, and PRK Using Multivariate Regression Analysis.

The ratio of posterior-to-anterior curvature radii of the cornea (P/A ratio) is an important element in determining corneal refractive power. P/A ratio has been well studied in patients prior to undergoing refractive surgery, but its postoperative value remains less so. We aimed to examine the value of preoperative characteristics of refractive surgery patients in predicting the 1-year postoperative P/A ratio in LASIK, PRK, and SMILE using both linear and multivariate regression analyses. This was a retrospective study that included patients with manifest refraction spherical equivalents (MRSE) from -7.71D to -0.25D. In total, 164 eyes underwent LASIK, 183 underwent PRK, and 46 underwent SMILE. All patients had preoperative and 1-year postoperative front sagittal and back sagittal keratometry measurements at 4, 5, and 6 mm around the corneal vertex. Postoperative P/A after LASIK, PRK, and SMILE was found to be significantly correlated with MRSE and preoperative P/A. Stepwise variable selection in multivariate regression revealed that spherical equivalent was the most significant predictor of postoperative P/A. When coupled with other preoperative characteristics, including P/A, age, asphericity, and keratometry, the multivariate regressions were able to produce models with high predictive value in LASIK (adjusted R2: 0.957), PRK (adjusted R2: 0.934), and SMILE (adjusted R2: 0.894).

Influence of Preoperative Parameters on the Ratio of Keratometric Change per Diopter of Attempted Spherical Equivalent (∆K/∆SEQ) for Myopic Correction Within LASIK, PRK, and SMILE.

Purpose: To compare 3 of the most common corneal refractive procedures; PRK, LASIK, and SMILE assessing ΔK/ΔSEQ ratio and its correlation with preoperative demographics including age, keratometry, pachymetry, cylinder value, and attempted myopic correction. The goal was to analyze the relative strength of each preoperative parameter in accounting for changes in ∆K/∆SEQ. Patients and Methods: A total of 370 eyes from 102 male and 97 female patients (173 eyes PRK, 153 LASIK, and 44 SMILE) with ages ranging from 20 to 51 underwent refractive surgery for myopia between -0.25 and -7.71 D manifest refraction spherical equivalent (MRSE). All surgeries were performed at a single surgery center in Draper, Utah. The Pentacam was used for all optical measurements and data were gathered pre-operatively and then again 1-year post-operatively. Only patients who achieved emmetropia at a visual acuity of 20/25 or better were included. Results: The mean ΔK/ΔSEQ ratio for LASIK (0.839 ± 0.020) was significantly greater than that of PRK (0.775 ± 0.022) and SMILE (0.709 ± 0.046). Age was found to negatively correlate with ΔK/ΔSEQ for both LASIK (r = -0.177) and SMILE (r = -0.451) procedures. Pre-op keratometry was found to negatively correlate with ΔK/ΔSEQ for LASIK (r = -0.202) but not for PRK or SMILE. Pre-op pachymetry was not correlated with ΔK/ΔSEQ for any of the procedures. Attempted myopic spherical equivalent (SEQ) correction was positively correlated with ΔK/ΔSEQ for LASIK (r = 0.236), PRK (r = 0.459), and SMILE (r = 0.304). Lastly, pre-op cylinder value was found to be correlated to ΔK/ΔSEQ in SMILE (r = -0.367), but not in LASIK or PRK. Conclusion: The ΔK/ΔSEQ ratio not only differs depending on the procedure being done but also by pre-operative factors such as age, keratometry, attempted correction, and cylinder value. Multiple linear regression analysis revealed that the attempted correction had the greatest effect on ∆K/∆SEQ out of all parameters in LASIK and PRK. For SMILE, age had the greatest predictive value of the change in ∆K/∆SEQ. While the exact effect of these parameters will vary by surgeon, all of these should be factored into a refractive surgeon's nomograms in order to achieve optimal visual outcomes for their patients.