PURPOSE:To compare automated cyclotorsion compensation using the WaveLight® Topolyzer™ system with manual cyclotorsion alignment guided by the Callisto image-guided system in achieving accurate astigmatic correction during femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS:This retrospective, single-center study analyzed data from 159 eyes that underwent FS-LASIK with a 6-month postoperative follow-up. Group 1 (n = 113) received real-time automated cyclotorsion compensation using the WaveLight® Topolyzer™ system, whereas Group 2 (n = 46) underwent manual cyclotorsion alignment guided by the Callisto image-guided system when automated registration was not feasible. Postoperative uncorrected (UDVA) and corrected (CDVA) distance visual acuity, residual refractive astigmatism, and vector analysis parameters-including target-induced astigmatism (TIA), surgically induced astigmatism (SIA), correction index (CI), difference vector (DV), and index of success (IOS)-were evaluated at 1 and 6 months. RESULTS:Baseline cylindrical refractive error was comparable between the groups (p = 0.661). At 6 months, mean residual astigmatism was -0.28 ± 0.26 D in Group 1 and -0.19 ± 0.22 D in Group 2, although the between-group difference did not reach statistical significance (p = 0.051). Group 2 achieved significantly better UDVA at 6 months (0.01 ± 0.02 logMAR) compared with Group 1 (0.04 ± 0.07 logMAR; p = 0.019). Vector analysis demonstrated a lower difference vector and a slightly higher correction index in Group 2, indicating more precise long-term astigmatic alignment. CONCLUSIONS:Both automated and image-guided cyclotorsion control strategies produced excellent visual and refractive outcomes after FS-LASIK. However, image-guided manual alignment using the Callisto system was associated with superior uncorrected visual acuity and a more favorable vector profile, supporting its use as an effective alternative when automated cyclotorsion registration is limited.
PURPOSE:To determine whether growth differentiation factor 15 (GDF15) is detectable and elevated in tears of patients with primary open-angle glaucoma (POAG) and whether tear GDF15 levels correlate with aqueous humor (AH) GDF15 levels. METHODS:In a single-center cross-sectional study, we recruited 21 patients undergoing ocular surgery, including patients with moderate to severe POAG undergoing glaucoma or cataract surgery (n = 11) and controls without glaucoma undergoing cataract surgery (n = 10). Demographic data were obtained by chart review. Tear samples were obtained preoperatively using Schirmer strips, and AH samples were obtained from the initial limbal paracentesis during surgery. GDF15 concentrations were quantified using enzyme-linked immunosorbent assay. RESULTS:AH GDF15 levels were significantly elevated in POAG samples compared with controls (p = .0057), and this difference remained significant after normalization to total protein (p = .0193). GDF15 was detectable in nearly all tear samples and was significantly higher in POAG patients than in controls (p = .0003), remaining significant after normalization (p = .0022). Raw tear and AH GDF15 levels were not significantly correlated (p = .0736, R2 = 0.1588) but showed significant positive correlation after normalizing to total protein and removing two outliers (p = .0019, R2 = 0.4416). CONCLUSION:Tear GDF15 is detectable and significantly elevated in POAG patients. Tear GDF15 correlates with AH GDF15 after normalization to total protein. These findings suggest the potential of tear GDF15 as a noninvasive molecular biomarker of POAG and highlight the importance of larger studies to validate these findings.
PURPOSE:Retinal degeneration (RD) is the common ocular pathogenesis characterized by photoreceptor cell dysfunction. Increasing evidence has shown that the accumulation of 4-hydroxynonenal (4-HNE) is closely associated with RD. Ginkgo biloba special extract EGb 761 has been widely used to prevent and treat certain diseases. In this study, we investigated the effect of EGb 761 on photoreceptor cell damage in retinal degeneration and related mechanism. METHODS:Balb/c mice and 661w cells were used in vivo and in vitro. CCK8 was used to measure the cell viability after 4-HNE or EGb 761 treatment. Apoptosis was evaluated by TUNEL staining. Related gene expression was measured by qRT-PCR and Western blot. Autophagy was observed by TEM and autophagy flux. ROS production was measured using the DCFH-DA probe. RESULTS:Electroretinography and H&E staining showed that retinal function and morphology were impaired and the expression of LC3 and p62 was decreased or increased and the expressions of anti-oxidative stress-related genes Trx1, Sod2 and Glrx1 were reduced after light damage, EGb 761 treatment ameliorated these processes. After 4-HNE treatment in vitro, the fraction of apoptotic cells was increased and the expression of Bax was increased and Bcl2 was decreased. ROS generation was increased and the expression of Sod2 and Glrx1 was reduced. Furthermore, autophagy was dysregulated, the expression of p62 was increased, and the LC3II/LC3I level was decreased. TEM and autophagic flux showed that autophagosomes accumulated. EGb 761 treatment alleviated these impairments. However, apoptotic cells increased significantly, ROS generation increased and the expression of p-AMPK, p-ERK and Nrf2 was decreased after AMPK inhibitor Compound C treatment, compared with 4-HNE and EGb 761 alone treatment groups. CONCLUSION:EGb 761 exerts a protective effect on photoreceptor cell damage in retinal degeneration. This process was associated with a modification of the AMPK/ERK signaling pathway that regulates oxidative stress and autophagy.
PURPOSE:Diabetic retinopathy (DR) is the leading cause of preventable blindness among working-age adults. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), first-line treatments for diabetes mellitus (DM), have demonstrated efficacy in decelerating DR progression. However, the mechanisms remain unclear. This study investigates how canagliflozin (CANA), an SGLT2 inhibitor, exerts neuroprotective effects in DR by suppressing microglial proinflammatory cytokine release. MATERIALS AND METHODS:Using high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice and BV-2 microglial cells under high glucose (HG) conditions, we elucidate the mechanistic link between CANA and neuroinflammation suppression in DR. Retinal structure and function were assessed using optical coherence tomography and electroretinography. Protein was evaluated via Western blotting, immunostaining, and enzyme-linked immunosorbent assay. Cell viability was measured using the Cell Counting Kit-8 assay. RESULTS:CANA demonstrated significant neuroprotective effects in diabetic retinopathy (DR) by attenuating microglia-mediated neuroinflammation. In HFD and STZ-induced diabetic mice, the ganglion cell complex thickness and a-wave and b-wave amplitudes decreased (p < 0.05). CANA upregulated the ganglion cell complex thickness (p < 0.05) and TSPO expression (p < 0.05), and tended to increase a-wave and b-wave amplitudes (p > 0.05) in retinas in DM mice. In BV-2 cells, HG activated BV-2 cells, downregulated TSPO expression, and promoted proinflammatory cytokine release, toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) expression, and nuclear translocation of p65 and phosphorylated p65 (p < 0.05). CANA reduced BV-2 cell viability, upregulated TSPO, while suppressing proinflammatory cytokine release, TLR4 and NLRP3 expression, and nuclear translocation of p65 and phosphorylated p65 (p < 0.05). Notably, CANA inhibited the TLR4/NF-κB/NLRP3 pathway, evidenced by reduced TLR4/NLRP3 protein levels and diminished nuclear translocation of p65 and phosphorylated p65 in microglia. CONCLUSIONS:These findings identify CANA as a promising therapeutic candidate for DR, acting through TLR4/NF-κB/NLRP3-dependent modulation of microglial activation.
PURPOSE:Recent observational studies have revealed gut microbiota influences the development and progression of several retinal diseases. However, the causal relationship between gut microbiota and central serous chorioretinopathy (CSCR) are still not understood. METHODS:The data of gut microbiota and circulating immune cell traits were identifed from large‑scale genome‑wide association studies (GWAS) summary data, and the data of CSCR come from FinnGen database.Mendelian randomization (MR) was used to investigate the causal relationships between gut microbiota, circulating immune cells, and CSCR. Mendelian randomization methods included inverse variance weighting and Bayesian weighting. Cochran's Q, Egger intercept, and MR-PRESSO were used to evaluate heterogeneity, genetic pleiotropy, and horizontal pleiotropy. Sensitivity was evaluated using leave-one-out method.Finally, we explored whether immune cell act as a mediating factor in the pathway from gut microbiota to CSCR. RESULTS:12 gut microbiota traits were associated with increased genetic risk of CSCR, 2 were associated with decreased genetic risk of CSCR.Mediated mendelian randomization analysis identified 10 pathways through which gut microbiota affects the genetic prediction of CSCR through circulating immune cell mediation, with Demequinaceae via IgD-CD24-% lymphocyte (7.0%) and CD24 on sw mem (3.5%), Demequina via IgD-CD24-% lymphocyte (9.6%), GCA-900066575 sp900066385 via CD4 on CD28 + CD4+ (9.7%), Saccharofermentanaceae via CD45 on HLA DR+T cells (4.7%), CD80 on plasmacytoid DC (5.0%), and CD80 on CD62L + plasmacytoid DC (5.9%), UBA737 via HLA DR+CD8br AC (4.3%), CAG-1000 sp000434555 via Resting Treg% CD4 Treg (3.3%) affecting the genetic risk of CSCR. CONCLUSIONS:Our mediated mendelian randomization analysis provides genetic evidence suggesting that circulating immune cells may mediate the causal relationship between gut microbiota and CSCR. The identified associations and mediation effects offer new insights into potential therapeutic avenues for CSCR.
PURPOSE:To determine whether the presence of an epiretinal membrane (ERM) predicts treatment outcomes following intravitreal dexamethasone implant (DEX) in eyes with persistent diabetic macular edema (DME). METHODS:This is a retrospective cohort study of patients with persistent DME seen at a single academic center over a 10-year period from 2014-2025. Persistent DME was defined as retinal thickness greater than 300 microns despite anti-VEGF treatment for at least 6 months and three injections. Patients were excluded for non-diabetes causes of secondary ERM, vitreomacular adhesion or traction, prior steroid treatment or vitreoretinal surgery, or recent laser or other surgery. Forty-seven eyes from 41 patients met the inclusion criteria. Eyes were categorized based on ERM status, and outcomes were compared. The primary outcomes were changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to 3 and 6 months following DEX. RESULTS:Twenty-six of 47 (55%) eyes had an ERM. Demographics, treatment history, and baseline anatomic characteristics were similar between the ERM and non-ERM groups. Baseline BCVA was worse in the ERM group. Patients with an ERM trended toward greater improvement in visual acuity following DEX than patients with no ERM; however, this difference was not statistically significant. Similarly, improvements in CST, center maximum thickness, and retinal volume were greater in the ERM group but failed to reach statistical significance. CONCLUSIONS:The presence of an ERM was associated with directionally greater visual and anatomic improvements following DEX treatment, however this was not statistically significant after accounting for baseline CST, baseline BCVA, PDR, and prior PRP.
PURPOSE:To compare macular vessel density (VD) between Duane syndrome (DS) patients and healthy controls using optical coherence tomography angiography (OCTA). METHODS:In this prospective study, age- and sex-matched DS patients and healthy controls underwent OCTA using a Topcon DRI OCT-1 Triton device. VD was measured in the superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR), and choriocapillaris (CC) across five macular quadrants (central, nasal, temporal, superior, inferior). The Benjamini-Hochberg procedure was applied to control the false discovery rate (FDR) across 20 primary comparisons. Generalized estimating equations accounted for inter-eye correlations. RESULTS:The study included 114 eyes from 64 participants (29 DS patients, 43 eyes; 35 control subjects, 71 eyes). Groups were comparable in age, sex, axial length, and other baseline characteristics (all p > 0.05). Before correction, DS patients showed nominally higher central SCP VD (22.55 ± 5.9% vs. 21.8 ± 5.2%, p = 0.031) and nominally lower VD in the DCP inferior quadrant (45.81 ± 5.7% vs. 48.19 ± 2.6%, p = 0.011), CC temporal quadrant (53.32 ± 2.6% vs. 54.21 ± 1.9%, p = 0.037), and CC superior quadrant (51.09 ± 3.5% vs. 52.7 ± 2.5%, p = 0.010). After Benjamini-Hochberg FDR correction, none of these differences retained statistical significance (all q > 0.05). No differences were observed in the OR (all p > 0.05). CONCLUSION:In this clinical study, no statistically significant macular vascular differences were identified between DS patients and healthy controls after rigorous correction for multiple comparisons. However, observed trends toward central SCP hyperperfusion and regional DCP and CC hypoperfusion generate hypotheses regarding potential mechano-vascular effects of chronic extraocular muscle co-contraction in DS. These findings warrant confirmation in larger prospective cohorts with pre-specified primary outcomes.
PURPOSE:To investigate the effects of morning and evening narrowband blue light exposure on axial length, and to examine the short-term effect of morning blue light combined with myopic defocus on axial length. METHODS:For objective 1, 18 individuals underwent 60 minutes of narrowband blue light exposure (460 nm) in the morning (9:00-11:00 AM) and evening (5:00-7:00 PM) of the same day. The axial length values were normalized to the average of the morning and evening axial length values. For objective 2, 27 young adults were exposed to 60 minutes of narrowband blue light while wearing a + 3.00 D lens over the right eye. Broadband white light was the control condition in both experiments. Axial length was measured using Lenstar LS900. RESULTS:In the first objective, a significant reduction in axial length was observed after exposure to morning blue light compared to evening blue light (-10.0 ± 3.96 µm vs.-0.67 ± 3.30 µm; p = 0.02), whereas no such effect was observed with broadband white light exposure (0.0 ± 3.53 µm vs. -2.50 ± 4.23 µm, p = 0.70). While the broadband white light exposure did not alter the normal diurnal variation in axial length (+2.35 ± 1.82 µm vs.-6.25 ± 2.21 µm, p = 0.04), blue light diminished such a pattern (-4.12 ± 1.72 µm vs. -2.00 ± 2.00 µm, p = 0.48). In the second objective, the myopic defocus did not influence axial length under either narrowband blue or broadband white light conditions. CONCLUSION:The short-term narrowband blue light exposure led to a significant decrease in axial length in the morning than evening exposure, with a likely influence on the daily variation of the morning-evening difference in axial length. Morning blue light exposure with lens-induced myopic defocus did not provide additional short-term modulation of axial length.
There is a growing interest in identifying potential biomarkers that can objectively serve as tools for diagnosis, monitoring, and treatment of ocular chronic pain. Although pain is a biological warning signal absolutely necessary for our survival, when it lasts for 3 or more months it becomes chronic and then it is considered a disease by itself. Chronic pain is a very disabling condition/disease which highly impairs the quality of life of patients. Development of ocular chronic pain, persistent and of high intensity, is present in some patients with dry eye disease (DED), or it can be triggered by some pathological events or after surgical procedures. However, in many of these cases the ocular clinical examination is apparently normal, and the explanation of that pain is not obvious. This type of pain is also difficult to treat because its pathophysiological mechanisms are not completely understood yet, and there are no standard criteria for its diagnosis. Several tear fluid biomarkers have been presented for different ocular diseases, and also for non-ocular, systemic diseases. Different studies have addressed the analysis of tear molecular profiles, including proteins, cytokines and neuromediators such as IL-9, MIP-1α, IL-10, IL-8, TNF-α, IL-6, Fractalkine, IL-1RA, Substance P, CGRP, NPY, and NGF levels associated with the presence of chronic ocular pain. Additionally, the preoperative tear levels of CGRP have been shown as predictive risk factor for ocular pain development after refractive surgery. These specific molecular profiles might help to explain the differences in symptomatology and clinical parameters in patients suffering from ocular pain and to identify those subjects more prone to develop it. Understanding the molecular bases underlying ocular pain will help in the search for effective, selective, and personalized therapies.
PURPOSE:Understanding the mechanisms of dynamic accommodation is essential for improving the understanding and management of progressive myopia. This study compared dynamic and residual accommodation patterns between stable and progressive myopes. METHODS:Accommodative response, residual accommodation, microfluctuations, and response times were assessed in 18 myopic participants classified as stable (n = 10) or progressive (n = 8). Measurements were obtained in the relaxed state and during/after 1.00D, 2.45D, and 4.73D stimuli using a real-time Shack-Hartmann aberrometer. RESULTS:Progressive myopes showed higher residual accommodation after 2.45D (p = 0.014) and 4.73D (p = 0.008), a pattern not observed in stable myopes. They also exhibited greater accommodative instability, with significantly increased microfluctuations during 4.73D stimulus (p = 0.001). Regarding residual accommodation, microfluctuations increased after removal of the 1.00D and 2.45D stimuli in both stable (p = 0.008; p = 0.032) and progressive myopes (p = 0.002; p = 0.016), although values after 2.45D were significantly higher in progressive myopes than in stable myopes (p = 0.042). Progressive myopes also showed longer disaccommodative response time after the 2.45D stimulus (p = 0.032). CONCLUSIONS:Although accommodative responses during stimulation were similar between stable and progressive myopes, residual accommodation, microfluctuations, and disaccommodative response times differed between groups and may represent relevant factors in progressive myopia.
PURPOSE:To evaluate retinal microvascular alterations in patients with intermittent exotropia (IXT) using optical coherence tomography angiography (OCTA), with particular emphasis on differences between suppressed and non-suppressed eyes and their relationship with deviation magnitude. MATERIALS AND METHODS:In this prospective observational study, patients with IXT and age and sex matched healthy controls underwent macular OCTA imaging. Vessel densities of the superficial (SCP) and deep capillary plexuses (DCP), as well as the foveal avascular zone (FAZ) area, were quantified and analyzed across four quadrants (superior, inferior, nasal, and temporal). Intergroup comparisons were performed among suppressed, non-suppressed, and control eyes, and subgroup analyses were conducted based on deviation magnitude (<40 and ≥40 prism diopters). RESULTS:Among 57 patients with intermittent exotropia (114 eyes) and 57 healthy controls (57 eyes), no significant differences were found in SCP vessel densities across groups (p > 0.05). In contrast, DCP vessel density was significantly higher in the nasal (p = 0.001) and superior (p = 0.015) quadrants of both suppressed and non-suppressed eyes compared with controls, with no interocular differences between the two eye groups. The FAZ area likewise showed no significant variation among groups (p = 0.776). Subgroup analysis demonstrated that the increase in nasal DCP vessel density persisted in both small to moderate (<40 prism diopters) and large angle (≥40 prism diopters) exotropia. CONCLUSIONS:Patients with IXT exhibited quadrant-specific increases in DCP vessel density in both suppressed and non-suppressed eyes compared with healthy controls, whereas SCP vessel density and FAZ area remained unchanged. The absence of interocular differences in DCP vessel density suggests that the observed retinal microvascular alterations are associated with IXT regardless of suppression status.
PURPOSE:Isotretinoin reduces the production and spread of sebaceous glands in the skin but can also affect the sebaceous glands of the eyelids, the meibomian glands, leading to dry eye disease (DED). The purpose of this study is to systematically review the evidence regarding the effects of isotretinoin on ocular surface parameters and its association to DED. METHODS:A systematic search was conducted in MEDLINE (via Ovid), Embase, Scopus, and the Cochrane Central Register of Controlled Trials databases. Independent screening of titles, abstracts and full-text articles was performed by two authors. RESULTS:A total of 43 articles were included in this review. Across prospective studies evaluating ocular surface parameters, worsening of dry eye symptoms and objective signs of ocular surface disease was frequently reported, particularly for measures of meibomian gland structure and function. Six studies evaluated interventions intended to reduce isotretinoin-associated adverse effects, of which four reported improvements in symptoms or ocular surface parameters. CONCLUSION:Dry eye disease appears to be a common and potentially serious side effect of isotretinoin. The drug may cause persistent alterations to the sebaceous glands in some patients, although the long-term extent and clinical significance remain uncertain. Patients should be informed about potential ocular complications and screened for symptoms of DED before and during isotretinoin treatment.
PURPOSE:To establish an abnormal blinking murine model to serve as a reproducible platform for investigating mechanical force-induced ocular surface damage. METHODS:Abnormal blinking was induced in female C57BL/6J mice using a mini-reciprocating device at 10 or 40 blinks/min for 20 min/day over 3 days (AB-10 and AB-40 groups). Normal-blinking mice (BC group) and lacrimal gland ConA-injected mice served as controls. Tear film stability, tear secretion, and corneal fluorescein staining were evaluated longitudinally on days 7, 14, and 21. Subbasal nerve plexus (SNP) alterations, epithelial remodeling, and corneal ultrastructure were evaluated longitudinally up to day 21 via IVCM, histological, and TEM/SEM analyses. RESULTS:Both AB groups exhibited comprehensive disruptions of ocular surface homeostasis. These changes were by significantly increased corneal fluorescein staining (p < 0.001) and reduced TUBT and tear secretion from day 7 through day 21. IVCM and TEM/SEM revealed that subbasal nerve fibers largely disappeared by day 7, accompanied by prominent corneal stromal cell activation, acute corneal edema, and severe epithelial ultrastructural degradation (loss of microvilli, cell apoptosis, and shedding). Most of these acute alterations gradually resolved by day 21, with the AB-40 group exhibiting the most severe, prolonged damage and delayed homeostatic recovery. CONCLUSIONS:Abnormal blinking mice model establishes a stable, reproducible model of mechanical force-induced ocular surface homeostasis damage, the model may be a mixed effect of blinking-induced acute mechanical microtrauma and secondary tear film function impairment. This research provides a valuable in vivo tool for investigating the mechanisms of biomechanical action in ocular surface diseases.
PURPOSE:The loss of SOX2+GJA1- lens epithelial stem cells, along with a decrease in sphere-forming ability, was observed in the central zone of cataractous lenses. Nuclear localization of Yes-associated protein (YAP) has been associated with stemness in various tissues, and its conditional knockout was reported to develop cataract in mice. This study aims to investigate the expression of YAP and SOX2, along with other YAP signaling genes, in the anterior human lens epithelium of normal and cataractous lenses. METHODS:Whole mounts of human anterior lens epithelium from normal and cataract lenses were immunostained for SOX2, YAP, and α-SMA, followed by confocal microscopic analysis. Further, the expression of YAP signaling genes was analyzed by Western blot. RESULTS:Nuclear expression of SOX2 and YAP was identified in the central (7.25 ± 3.63% of cells) and equatorial (9.15 ± 6.09% of cells) zones of normal lens epithelium. Such cells were absent in cataractous lenses along with a significant reduction in nuclear YAP expression. Western blot analysis confirmed the increased pYAP/YAP ratio and decreased MST2 and LATS1 in cataractous lens compared to normal lens epithelium. Furthermore, α-SMA expression was elevated in cataractous lens epithelium, indicating its association with cataract development. CONCLUSION:The absence of SOX2+YAP+ cells in cataractous lenses indicated the possible association between stem cells and cataract development. Further studies are essential to elucidate the role of YAP signaling in the pathogenesis of cataract.
PURPOSE:Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability, hyperosmolarity, and inflammation. Although the exact etiology may vary between patients, inflammation remains a central pathogenic mechanism. Key inflammatory pathways in DED include T-cell activation and the upregulation of cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinases (MMPs). Cyclosporine A (CsA) is an immunomodulatory agent that reduces ocular surface inflammation by inhibiting calcineurin, thereby suppressing T-cell activation. METHODS:This narrative review summarizes the available evidence on the role of topical CsA 0.09% in DED, including its formulation characteristics, mechanism of action, efficacy, safety, and tolerability. Relevant preclinical and clinical studies of the aqueous nanomicellar formulation of CsA 0.09% (OTX-101 0.09%) were reviewed. RESULTS:Conventional ophthalmic preparations of CsA are oil-based or oil-in-water emulsions, which have several limitations, including poor ocular tolerability and a slow onset of efficacy. An aqueous nanomicellar formulation of CsA 0.09% (OTX-101 0.09%) has been approved by the US Food and Drug Administration and the European Medicines Agency. It is widely used for treating DED, enhancing ocular bioavailability while improving ocular tolerability. Clinical studies have demonstrated that nanomicellar CsA 0.09% therapy significantly improves both signs and symptoms of DED, supporting its utility as an effective and well-tolerated treatment option. CONCLUSION:Nanomicellar CsA 0.09% therapy significantly improves both signs and symptoms of DED, supporting its utility as an effective and well-tolerated treatment option.
PURPOSE:Optic neuritis (ON) is a common inflammatory disease of the optic nerve that usually precedes serious neurological disorders. The purpose of this study was to explore the causal relationship between immune cells and ON. METHODS:We adopted a bidirectional Mendelian randomization (MR) approach, analyzing genetic variants associated with 731 immune cells from a Sardinian cohort and ON data from the FinnGen consortium. Instrumental variables (IVs) for each phenotype were stringently selected based on linkage disequilibrium and genome-wide significance levels. Inverse-variance weighted (IVW) served as the primary analysis method, supplemented by sensitivity analyses to assess the robustness of findings. RESULTS:The study identified 2776 SNPs as IVs for 731 immune cells. The bidirectional MR analysis revealed that 11 immune cells were significantly associated with ON, with 9 positively correlated and 2 negatively correlated with ON risk. Among them, human leukocyte antigen receptor (HLA-DR)++ monocyte proportion showed the strongest association as a risk factor (OR = 1.828, 95% CI = 1.515-2.206, p = 3.13 × 10-10). The robustness of the findings was confirmed through heterogeneity and pleiotropy tests, and the relationship persisted even after adjusting for confounders using multivariate MR analysis. Only the HLA-DR++ monocyte remained a significant risk factor after multiple testing corrections. CONCLUSIONS:Specific immune cells, notably HLA-DR++ monocytes, critically influence ON pathogenesis, suggesting biomarkers and therapeutic targets. This MR study provides genetic insights into immune-mediated ON mechanisms.
Purpose: Tear film disorders, particularly dry eye disease (DED), are among the most common ocular surface conditions and arise from dysfunction of the lacrimal functional unit, including the lacrimal gland, meibomian glands, and conjunctival goblet cells.Despite the recent advancements in the management of the tear film disorders, the treatment still remains palliative. Hence there is a need for research focusing on regenerative approaches to restore the physiological functions and homeostasis of the tear film.Methods: A selective literature review was performed using PubMed, Google Scholar, and Medline. The review is based on 127 relevant publications published up to January 2026, with emphasis on experimental and translational approaches for restoring tear film homeostasis. In addition, the latest advances in lacrimal gland regeneration are described, including recent studies conducted by our research group.Results: This review aims to first give an overview about the underlying diseases which alters the tear film composition, secondly highlighting the current treatment methods and their limitation and finally analyze recent experimental strategies that promotes tear film regeneration including stem cell-based therapies, tissue engineering of the lacrimal gland, neurotrophic factor supplementation, gene therapy, and biomaterial-assisted delivery systems.Conclusion: Regenerative approaches for tear film disorders are evolving from symptomatic management toward restoration of functional tissue. Although most strategies remain in preclinical or early translational stages, advances in stem cell biology, biomaterials, secretome research, and tissue engineering provide a promising foundation for future therapies targeting the lacrimal functional unit and long-term tear film homeostasis. By summarizing current findings and identifying research gaps, this review can highlight promising approaches for translational research and potential clinical applications.
