Medical hypothesis discovery and innovation in ophthalmology

Background: Keratorefractive lenticule extraction (KLEx) has become a widely used corneal refractive surgery. Since its approval by the United States Food and Drug Administration (FDA), there are relatively few studies from the U.S. that have evaluated KLEx visual outcomes, often limited by their small sample size and short follow-up duration. To evaluate the one-year visual outcomes using KLEx for myopia and myopic astigmatism in a large U.S. cohort.
Methods: This was a retrospective study of 577 eyes from 314 patients who underwent KLEx between March 2017 and May 2024 at a single refractive surgery center. Inclusion criteria were myopia between -9.25 to -1.00 D, cylinder up to -3.00 D, and preoperative corrected distance visual acuity (CDVA) of 20/20 or better. The uncorrected distance visual acuity (UDVA), CDVA, manifest refraction, and complications were evaluated at 3 and 12 months postoperatively. Clinical outcomes were also compared to the U.S. FDA premarket trials and large international cohorts.
Results: Of 577 treated eyes, data were available at 3 months for 511 eyes (88.6% follow-up) and 12 months for 440 eyes (76.3% follow-up). The mean spherical equivalent (SEQ) improved from -5.35 ± 1.62 D (-9.63 to -1.38 D) to -0.04 ± 0.44 D (-1.88 to 1.88 D) (P < 0.001). Mean cylinder improved from -0.66 ± 0.66 D (-3.00 to 0.00 D) at baseline to -0.40 ± 0.32 D (-1.75 to 0.00 D) at 12 months (P < 0.001). Additionally, postoperative UDVA was 20/20 or better in 81% of eyes and 20/25 or better in 94% of eyes. Postoperative SEQ was within ±0.50 D in 85% of eyes and within ±1.00 D in 97% of eyes at 12 months. The SEQ remained stable across all postoperative visits, with a mean change of -0.03 ± 0.38 D from 3 to 12 months. There was a gain of one line of CDVA in 16% of eyes at 12 months, with no eyes losing two or more CDVA lines. Target-induced and surgically induced astigmatism were strongly correlated at both 3 and 12 months, with a mean undercorrection of 20% by one year (R² = 0.69).
Conclusions: KLEx demonstrates predictable and safe correction of myopia and myopic astigmatism over 12 months in a U.S. cohort. Visual outcomes meet or exceed the FDA benchmarks and are consistent with published literature, although a potential need for improved cylindrical correction remains.

Background: Glaucoma suspects (GS) exhibit risk factors such as elevated intraocular pressure (IOP), suspicious optic disc or retinal nerve fiber layer (RNFL) findings, or a positive family history, yet their risk of progression varies widely. Optical coherence tomography angiography (OCTA) and central corneal thickness (CCT) have emerged as important markers for detecting early structural and microvascular changes in GS patients. We aimed to estimate the predictive value of OCTA-derived metrics and CCT, and to assess their correlations in GS individuals.
Methods: This comparative cross-sectional study included eyes from GS patients and eyes from age- and sex-matched  healthy individuals as a comparison group. All participants underwent a detailed medical history and comprehensive ophthalmologic examination. Investigations included visual field perimetry; optical coherence tomography (OCT) to assess structural optic nerve head parameters, RNFL thickness, and ganglion cell layer (GCL) thickness; OCTA to measure papillary vascular density (PVD) and radial peripapillary capillary density (RPC); and non-contact specular microscopy to determine CCT.
Results: The GS group had a mean age of 36.9 years, with 52.4% male (n = 11). GS eyes showed significantly larger CDR values, reduced rim area, thinner RNFL and GCL, and lower CCT compared with healthy eyes (all P < 0.05). Mean RPC, quadrant-specific RPC values, and mean PVD were significantly reduced in GS individuals (all P < 0.05). CCT showed significant correlations with all vascular metrics and structural parameters (all P < 0.05), except disc area (P > 0.05). In univariate logistic regression all variables were associated with GS status. After multivariate adjustment, only CCT ? 506 µm remained an independent predictor. Receiver operating characteristic curve analysis showed good diagnostic performance for CCT (area under the curve [AUC] = 0.757) and mean RPC (AUC = 0.820) in identifying GS eyes.
Conclusions: Patients with GS revealed significantly lower structural parameters and vascular metrics compared with the healthy group, and only thin CCT remained an independent predictor of GS status. Both CCT and mean RPC demonstrated good diagnostic performance for identifying GS eyes.

Background: Exposure keratopathy is a common ocular complication in patients admitted to the intensive care unit (ICU) ward and may progress from superficial epithelial breakdown to corneal perforation, a vision-threatening emergency requiring timely management. Conventional treatments often necessitate urgent surgery, which is challenging in critically ill individuals who are unsuitable for surgical intervention. OmniLenz®, a customized bandage contact lens pre-lined with vacuum-dried Omnigen® amniotic membrane, offers a practical, non-surgical, bedside alternative for managing small corneal perforations. This study evaluates its clinical outcomes in ICU patients with a small corneal perforation secondary to exposure keratitis.
Methods: This prospective interventional case series included ICU patients with <1 mm corneal perforations secondary to exposure keratitis, recruited over a two-year interval. All patients underwent corneal scraping with culture and sensitivity testing, followed by targeted antimicrobial therapy. Under sterile conditions, a dehydrated amniotic membrane (Omnigen®) was applied beneath a customized bandage contact lens (OmniLenz®) at the bedside. Patients were examined daily using a portable slit-lamp and followed for one month. The primary outcome was perforation closure, defined by a negative Seidel test and anterior chamber reformation. Secondary outcomes included improvement in epithelial integrity, corneal infiltration, and ciliary injection.
Results: Five ICU patients, aged 18 to 70 years, with <1 mm corneal perforations secondary to exposure keratitis were included. All eyes demonstrated rapid tectonic recovery following Omnigen®/OmniLenz® device application. Anterior chamber reformation and a negative Seidel test were achieved by day 7 in four patients and by day 10 in one patient. Complete perforation closure occurred in all cases. Marked improvement in keratitis was observed, with full epithelial defect healing and resolution of corneal infiltrates in every patient, followed by stable grade 3 stromal scarring. No neovascularization, device-related adverse events, or treatment complications occurred during the one-month follow-up.
Conclusions: Omnigen®/OmniLenz® device provides a safe, effective, and non-invasive bedside treatment for small corneal perforations secondary to exposure keratitis in critically ill ICU patients. Its use enabled consistent tectonic restoration, rapid perforation closure, and resolution of infection-associated corneal pathology without procedure-related complications. This approach offers a practical alternative to urgent surgical intervention in patients unsuitable for operative care and may serve as a valuable addition to corneal perforation management protocols. Further studies with larger cohorts are needed to evaluate its safety and efficacy in larger perforations and to determine long-term outcomes, including corneal scarring and visual acuity.

Background: Glaucoma is a major cause of vision impairment and blindness, characterized by damage to retinal ganglion cells (RGC) at the optic nerve head (ONH). The pathomechanism underlying glaucoma is heterogeneous and theories explaining the pathomechanism can be categorized as mechanical, vascular, or immunological. This mini review explores the involvement of reactive oxygen species (ROS) and oxidative stress in these established mechanisms of glaucoma.
Methods: A review of literature was conducted using PubMed/MEDLINE, with the query including the following keywords: “antioxidants,” “glaucoma,” “glaucoma pathomechanism,” “immunological,” “intraocular pressure,” “mechanical,” “reactive oxygen species,” “ocular hypertension,” “oxidative stress,” and “vascular.” The date filter was set from January 2010 to September 2025. Papers that were relevant to ROS or oxidative stress in the glaucoma pathomechanism were thoroughly reviewed. Their reference lists were also reviewed for relevant papers, from which relevant papers of any date were included.
Results: Following a comprehensive literature search, 67 journal articles were selected for review. They revealed the role of ROS and oxidative stress in the mechanical, vascular, and immunological pathomechanism theories of glaucoma. In the mechanical theory, oxidative stress mediates RGC apoptosis and trabecular meshwork damage. In vascular processes, retinal causes oxidative stress and vice versa, thus causing RGC death and ONH damage. With the immunological theory, ROS is implicated in glial cell and inflammasome activity that causes RGC injury. Key players in the generation of oxidative stress including NADP oxidase 2, dynamin-related protein 1, mitofusin 2, nuclear factor (erythroid-derived 2)?like 2, and nitric oxide. Conversely, various antioxidant factors are also implicated in glaucoma, however in oxidative stress conditions their effects are outweighed by those of ROS.
Conclusions: ROS and oxidative stress are important mediators in the glaucoma pathomechanism. They contribute to and unify the existing theories of mechanical, vascular, and immunological injury in glaucoma. Investigating specific oxidative stress players in the pathomechanism may reveal new therapeutic targets in the treatment of glaucoma.

Background: Uveal melanoma (UM) is an aggressive intraocular malignancy with high metastatic potential to the liver and poor prognosis. The nuclear factor kappa B (NF-?B) pathway, comprising the canonical and noncanonical branches, has been involved in UM development, tumor-microenvironment communication, and drug resistance. This review consolidates the evidence for NF-?B involvement in UM pathogenesis and therapeutic target value.
Methods: A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane CENTRAL database was performed from inception to June 2025. Studies investigating NF-?B activation, functional dependencies, genetic or microenvironmental modulators, or therapeutic interventions in UM were eligible. Included designs comprised original observational or experimental research, including mechanistic in vitro studies, animal models, and human tissue–based prognostic or correlative studies. English-language articles and relevant review studies addressing the research question were considered. Exclusion criteria included editorials, commentaries, conference abstracts with insufficient data, case reports lacking mechanistic insights, non-UM cancers without validated UM models, studies mentioning inflammation or NF-?B targets without direct NF-?B readouts, and those using pleiotropic inhibitors without genetic validation or pathway-specific evidence. Appropriate design-specific tools were applied to assess risk of bias.
Results: Canonical NF-?B signaling is mechanistically related to UM cell survival, proliferation, and migration, as shown by pharmacologic inhibition like BAY11-7082, and niclosamide and genetic modulation like microRNA-9. Noncanonical signaling is associated with invasive, immune-replenished tumors and liver metastasis yet has limited direct functional data. Deficiency in BRCA1-associated protein-1 (BAP1) and tumor necrosis factor alpha-enriched microenvironments control NF-?B activity, but there is conflicting data on the function of BAP1. Therapeutic targeting of NF-?B consistently suppresses UM phenotypes in vitro and in vivo, but pleiotropic inhibitor effects require confirmation.
Conclusions: NF-?B signaling, particularly the canonical branch, is required for UM malignancy, while noncanonical signaling is linked with high-risk features. Branch-specific genetic manipulations and clinically relevant models should be employed in future research to maximize therapeutic strategies.

Background: Dry eye disease (DED) is one of the most prevalent and distressing ocular conditions worldwide, primarily resulting from alterations in the natural tear film that covers the ocular surface, often due to enhanced evaporation of its aqueous component. This process is frequently associated with dysfunction of meibomian glands (MGs), which are embedded within the tarsal plate of our eyelids and secrete the meibum, an oily mixture of proteins and lipids. Meibum forms the outermost layer of the tear film, playing a critical role in controlling water evaporation and stabilizing the tear film by lowering surface tension. Meibomian gland dysfunction (MGD) may result from structural abnormalities in the MGs, such as tortuosity, which impair the normal delivery of meibum. Increased laxity of the eyelid is also associated with development of MGD and DED, likely due to insufficient mechanical support for the glands, causing morphological changes.
Hypothesis: We designed and initiated the development of a non-invasive method to strengthen and stiffen the tarsal collagen containing the embedded MGs. By reducing tissue laxity, our aim is to halt further morphological deterioration of the glands and promote uniform and smooth delivery of meibum to the ocular surface. Our previous studies demonstrated that both mechanical tensile strength and rigidity (Young’s modulus) of tarsal collagen in animal and human eyelids were significantly enhanced by exposure to ultraviolet-A (UV-A) radiation with a wavelength of 365 nm in the presence of riboflavin as a photosensitizer.
Conclusions: We propose that applying this procedure at the initial manifestations of MGD and DED may prevent disease progression by restoring and preserving the normal morphology of the glands through reduced laxity, thereby ensuring proper secretion of the meibum into the tear film. The underlying principles and safety of the procedure were discussed in detail, and further pre-clinical evaluation steps were proposed and justified. Based on the proposed concept and the results of previous ex-vivo studies, in-vivo animal experiments and human clinical trials are currently in preparation.