Nevin Manimala

Vestn Oftalmol. 2026;142(1):60-69. doi: 10.17116/oftalma202614201160.

ABSTRACT

PURPOSE: This study aimed to investigate the morphological features of the lamina cribrosa (LC) of the scleral in terms of their potential role in optic nerve (ON) axonal injury.

MATERIAL AND METHODS: Longitudinal sections of the prelaminar, laminar, and postlaminar portions of the ON from human corneal donors were examined. Sections were stained with Masson’s trichrome and analyzed using the Bioscan AT+ software. Neurofilament (NF) expression was assessed immunohistochemically using the Neurofilament NE-14 antibody and quantified with ImageJ 1.54i. Statistical analysis included Pearson and Spearman correlation coefficients, as well as the Kruskal-Wallis, Mann-Whitney, and Kendall’s tau tests.

RESULTS: The ratio of connective tissue to neural components in the LC varied and correlated with age (χ²=21.09, p=0.0018). Based on these differences, three LC patterns were identified: mixed, elastic, and collagenous. The mixed LC pattern was most prevalent across all age groups; the elastic pattern predominated in younger individuals (<44 years); the collagenous pattern was most common in individuals older than 60 years. NF expression was lowest in the mixed type LC, increased significantly in the elastic type LC, and was highest in the >60-year age group with the collagenous type LC.

CONCLUSION: Remodelling of the LC of the sclera characterized by a predominance of collagenous tissue, primarily perivascularly, and accompanied by deformation of the anterior LC surface in individuals older than 60 years, together with a tendency toward increased deviation of ON axons passing through the LC, should be considered potential risk factors for ON axonal injury. The observed variability in the NF cytoskeleton, which preceded changes in axonal transport, may be used as an early marker of retinal ganglion cell damage.

PMID:41847809 | DOI:10.17116/oftalma202614201160

Vestn Oftalmol. 2026;142(1):14-20. doi: 10.17116/oftalma202614201114.

ABSTRACT

INTRODUCTION: The ability of the crystalline lens to change its shape is a key component of accommodation. As part of the lenticular theory of presbyopia, involutional changes in the lens substance itself are considered to be of primary importance. At the same time, the role of the capsule, which essentially serves as a structural, shape-modifying “framework” for the lens substance, remains insufficiently studied. Accordingly, one approach to clarification of the pathogenesis of presbyopia may involve investigating the relationship between potential changes in lens shape during accommodation and the biomechanical properties of its capsule.

PURPOSE: This study aimed to assess the potential relationship between accommodative stimulus-induced changes in the curvature of the anterior lens surface and the biomechanical parameters of the anterior capsule based on sequential clinical and experimental analysis.

MATERIAL AND METHODS: The study was conducted in a group of 11 patients (11 eyes, i.e., clinical observations) of presbyopic age scheduled for and undergoing standard phacoemulsification with intraocular lens implantation for uncomplicated cataract. Prior to surgery, the radius of curvature of the anterior lens surface was measured at baseline and under accommodative stimulus using the CASIA2 device (Tomey, Japan). Anterior lens capsule specimens with a diameter of 4.0-5.5 mm were obtained during surgery after continuous curvilinear capsulorhexis. The elastic modulus (Young’s modulus) of the specimens was determined using atomic force microscopy.

RESULTS: Correlation analysis involved the use of an integral parameter – the magnitude of change in the radius of curvature of the anterior lens surface induced by accommodative stimulus. A pronounced moderate positive correlation was identified between changes in the radius of curvature of the anterior lens surface and the elastic moduli of the outer and inner surfaces of the anterior capsule (r=0.560 and r=0.603, respectively). However, this relationship was statistically significant only for the inner surface of the capsule but not for the outer surface (p=0.050 and p=0.073, respectively).

CONCLUSION: This is the first study investigating the potential relationship between changes in the curvature of the anterior lens surface and the biomechanical properties of the anterior capsule using the same study object, which enabled sequential clinical (morphometric) and experimental (biomechanical) analyses. Based on the obtained results, age-related changes in the biomechanical properties of the lens capsule may be considered one of the factors within the lenticular theory of presbyopia development.

PMID:41847803 | DOI:10.17116/oftalma202614201114

Vestn Oftalmol. 2026;142(1):5-13. doi: 10.17116/oftalma20261420115.

ABSTRACT

INTRODUCTION: The structural approach to studying the mechanism of accommodation and its age-related changes focuses on analyzing morphometric parameters (size, shape, and position) of the crystalline lens as the key element responsible for changes in clinical refraction during accommodation. The latest-generation swept-source (SS) anterior segment optical coherence tomography (AS-OCT) device CASIA2 (Tomey, Japan) enables near-screening evaluation of lens shape and position both at baseline and under accommodative stimulus. In the latter case, the integrated optical system provides lens-induced accommodative stress directly in the examined eye.

PURPOSE: This study aimed to evaluate age-related changes in various morphometric parameters of the lens measured by CASIA2 OCT under accommodative stimulus.

MATERIAL AND METHODS: The study cohort comprised 74 healthy volunteers (123 eyes, i.e., clinical observations) aged 20-85 years. The exclusion criteria were clinically significant refractive errors and ocular diseases. Three groups were formed according to age: 20-30 years, 31-50 years, and >51 years (43, 33, and 47 clinical observations, respectively). Scanning was performed under conditions of relative accommodative rest and during accommodative stimulus. In the latter case, a lens-induced method of accommodative stimulus was used, employing a -5.0 D negative spherical lens and a fixation target in the form of a radial figure integrated into the optical system of the CASIA2 OCT device.

RESULTS: Analysis of the entire cohort (n=123) revealed significant changes in morphometric parameters of the lens under accommodative stimulus, including a decrease in the radius of curvature of the anterior (p=0.003) and posterior (p=0.045) lens surfaces, an increase in lens thickness (p=0.011) and nuclear thickness (p=0.007), as well as a reduction in lens diameter (p=0.026) and anterior chamber depth (p=0.033). The radius of curvature of the anterior lens surface under relative accommodative rest in Group 1 (20-30 years) was significantly higher (p=0.00) than in Groups 2 (31-50 years) and 3 (>51 years), with median values of 11.62, 9.47, and 9.25 mm, respectively. The magnitude of changes in lens curvature radius significantly decreased with increasing age for both the anterior and posterior surfaces. Baseline lens thickness and nuclear thickness increased significantly with age and also demonstrated an increase under accommodative stimulus across all age groups. A statistically significant correlation with age was found for the radius of curvature of the anterior surface (r=-0.371; p=0.00) and the posterior surface (r=-0.224; p=0.013), as well as for lens thickness (r=0.268; p=0.003).

CONCLUSION: Anterior segment OCT using the CASIA2 system is a highly informative method for assessing morphometric parameters of the crystalline lens under conditions of relative accommodative rest and lens-induced accommodative stress. Under accommodative stress, statistically significant changes included a decrease in the radius of curvature of the anterior and posterior lens surfaces, an increase in lens thickness and nuclear thickness, and a decrease in lens diameter and anterior chamber depth. Analysis of the magnitude of changes induced by accommodative stimulus and their correlation with age demonstrated statistically significant negative associations between age and the radius of curvature of the anterior and posterior lens surfaces, and a positive association with lens thickness.

PMID:41847802 | DOI:10.17116/oftalma20261420115

Wilderness Environ Med. 2026 Mar 18:10806032261426910. doi: 10.1177/10806032261426910. Online ahead of print.

ABSTRACT

IntroductionPharmaceutical stability is a key concern for space missions, where radiation, microgravity, and prelaunch repackaging may accelerate drug degradation. While prior studies examined medications in environmentally controlled spacecraft, data on vacuum exposure are limited. The Polaris Dawn mission provided an opportunity to evaluate drug content following depressurization of the Dragon spacecraft and exposure to the vacuum of space during extravehicular activity.MethodsNineteen medications (13 repackaged solid, 6 liquid) flew as part of the SpaceX medical kit and were analyzed with lot-matched terrestrial controls. All samples underwent ultra-performance liquid chromatography mass spectrometry analysis upon return. The primary outcome was the percent difference in active pharmaceutical ingredient (API) between vacuum exposure and ground controls. A secondary outcome was the absolute API content expressed as a percentage of labeled dosage.ResultsSeventeen of the 19 flown medications demonstrated a < 5% mean API difference between spaceflight and lot-matched terrestrial controls, remaining within the prespecified threshold for clinical significance. Seven medications showed statistically significant differences (p < 0.05) between the 2 groups, yet all but one medication remained within this 5% range. Against the narrow 95%-105% of labeled dosage criterion, 10 ground controls and 11 spaceflight-exposed medications fell outside this range. Expanding to the broader 80%-120% range, nearly all medications were within acceptable limits.ConclusionsShort-duration spaceflight with vacuum exposure resulted in modest differences in drug content between spaceflight and terrestrial samples. However, high concordance suggests no clinically meaningful degradation, supporting the feasibility of repackaged pharmaceuticals for commercial and exploratory missions.

PMID:41847800 | DOI:10.1177/10806032261426910

Biometrics. 2026 Jan 6;82(1):ujag043. doi: 10.1093/biomtc/ujag043.

ABSTRACT

Motivated by a multi-indication basket trial aiming to assess the efficacy of a novel biomarker-targeted therapy in gastric or gastroesophageal junction (G/GEJ), pancreatic, and other related cancers, we consider a statistical design and decision-making framework for such trials. Typically, the investigational therapy in the trial targets a biomarker that is present in multiple cancer indications, and patients with higher biomarker expression tend to exhibit higher response rates, assuming the targeting biomarkers are over-expressed in tumor cells. To enable information sharing across indications, the proposed SIMBA method introduces a Bayesian hierarchical model that defines positive and negative biomarker subgroups and identifies optimal go/no-go decisions. The operating characteristics of SIMBA are assessed via simulations and compared against existing methods in the literature. Overall, SIMBA is constructed to improve the identification of patient sub-populations who may benefit from biomarker-targeted therapeutics.

PMID:41847799 | DOI:10.1093/biomtc/ujag043

Int Health. 2026 Mar 18:ihag014. doi: 10.1093/inthealth/ihag014. Online ahead of print.

ABSTRACT

BACKGROUND: Implementing three months of once-weekly rifapentine and isoniazid (3HP) for tuberculosis preventive therapy among household contacts (HHCs) of bacteriologically confirmed pulmonary TB patients in India presents programmatic challenges requiring understanding from beneficiary and provider perspectives.

METHODS: From May 2023 to March 2024, nine focus group discussions were conducted across five rural and urban program settings: three with HHCs who received 3HP (n=28) and six with frontline healthcare providers (n=69) delivering the regimen within a multicentric implementation study. Descriptive thematic analysis explored experiences, perceptions, and implementation challenges.

RESULTS: Analysis of FGDs yielded four major themes: (i) perceptions and acceptance of 3HP; (ii) barriers to 3HP; (iii) advocacy and communication and social mobilization; and (iv) suggestions for improving 3HP. Participants appreciated the short, once-weekly regimen and family encouragement supporting adherence. However, reluctance to undergo testing without symptoms, fear of side effects, stigma, and access barriers limited uptake. Suggested solutions included transport support, mobile X-ray services, reminder tools, and family DOTS providers. Providers highlighted workforce shortages and the need for additional staff.

CONCLUSION: Both groups emphasized tailored counselling, strengthened community awareness, and media advocacy to improve uptake, adherence, and program sustainability of 3HP implementation at scale nationwide.

PMID:41847763 | DOI:10.1093/inthealth/ihag014

Stat Med. 2026 Mar;45(6-7):e70455. doi: 10.1002/sim.70455.

ABSTRACT

This commentary offers perspectives on delivering “rigorous causal inference on meaningful estimands” that differ from the opinions recently shared by Fleming et al. We (1) depict a more robust pathway for achieving this aim that incorporates clinical, causal and statistical reasoning, (2) suggest a tangibility criterion to judge the practical usefulness of an intercurrent event strategy, (3) illustrate the utility of causal inference methods in providing robust estimates when the clinical objective aligns with a hypothetical strategy, and (4) advocate for careful consideration of the tradeoffs between an estimand’s relevance and the required assumptions.

PMID:41847726 | DOI:10.1002/sim.70455

Diagn Interv Radiol. 2026 Mar 18. doi: 10.4274/dir.2026.263802. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the safety and efficacy of combined ethanol lavage and bleomycin sclerotherapy administered via a percutaneous pigtail catheter for the treatment of benign cervical cystic lesions.

METHODS: This retrospective study included 29 patients (mean age, 30 years; range, 4-60 years; male-to-female ratio, 16:13) who underwent bleomycin sclerotherapy following ethanol lavage via a pigtail catheter for benign cervical cystic lesions, including branchial cleft cysts, ranulas, thyroglossal duct cysts, lymphatic malformations, and epidermoid cysts, between March 2009 and September 2022. To explore potential predictors of treatment response, clinical diagnosis, baseline cyst size, and the total volume of injected sclerosant were evaluated. Statistical analyses included the paired t-test, chi-square test, and Mann-Whitney U test.

RESULTS: All patients were followed up for a mean duration of 18.2 months (range, 3-72 months) after the final treatment session. Complete cyst resolution was achieved in 17 of the 29 patients (59%), 8 patients (27%) demonstrated a volume reduction greater than 75%, and 2 patients (7%) exhibited a reduction of less than 75%; recurrence occurred in 2 patients (7%) despite repeated sclerotherapy. There were no significant differences between responders and nonresponders with respect to clinical diagnosis, baseline cyst volume, or total sclerosant dose. Minor procedure-related complications occurred in three patients (10.34%); no major complications were observed.

CONCLUSION: Combined ethanol lavage and bleomycin sclerotherapy administered via a percutaneous pigtail catheter is a safe and feasible treatment option for benign cervical cystic lesions.

CLINICAL SIGNIFICANCE: Combined ethanol and bleomycin sclerotherapy represents a safe, minimally invasive treatment option for benign cervical cystic lesions in routine clinical practice, with favorable outcomes and potential to reduce the need for surgical intervention.

PMID:41847722 | DOI:10.4274/dir.2026.263802

Stat Med. 2026 Mar;45(6-7):e70452. doi: 10.1002/sim.70452.

ABSTRACT

While the use of estimands in randomized trials is increasing, there is little guidance on which intercurrent event strategies should be used. The article by Fleming et al. seeks to address this gap. They argue that strategies such as hypothetical, principal stratum, and while-alive generally cannot be used to reliably inform decision making, and that treatment policy (and composite for mortality) strategies should be used instead. In this Commentary we argue that there are a variety of settings where strategies such as hypothetical, principal stratum, and while-alive can reliably inform decision-making and are preferable to a treatment policy strategy. We provide an alternative approach for selecting intercurrent event strategies, which systematically considers the trade-off between relevance (whether it addresses a useful question) and reliability (the ability to be estimated such that stakeholders can have confidence in the results) of each strategy in order to identify those that can be used to robustly inform decision-making. Our overall conclusion is that there is no single intercurrent event strategy that is appropriate in all settings; all strategies can be beneficial when used in appropriate settings, but harmful when used in inappropriate settings.

PMID:41847719 | DOI:10.1002/sim.70452

Stat Med. 2026 Mar;45(6-7):e70453. doi: 10.1002/sim.70453.

NO ABSTRACT

PMID:41847717 | DOI:10.1002/sim.70453