Search Results (101)

Corneal transparency depends on quiescence of stromal cells derived from neural crest cells and a well-controlled extracellular matrix. Disruption of this homeostasis causes fibrotic scarring, a leading cause of blindness. Transforming growth factor-β/Smad3 signaling drives corneal fibrogenesis, but the distinct roles of Smad2 versus Smad3 remain unclear. Smad2 ablation in neural crest cells using Wnt1-Cre mice triggers spontaneous severe corneal opacification along with massive stromal hypercellularity and fibrosis. The fibrotic phenotype occurs in the absence of injury, indicating that Smad2 is essential for balancing Smad3 activity in driving fibrotic signaling. Single-cell RNA sequencing and virtual knockout of Smad2 reveal prominent activation of Smad3-Yes-associated protein (YAP)/TEAD2-transcriptional program in Smad2-null corneas. Biochemical assays confirm that Smad2 loss results in increased Smad3 phosphorylation and formation of nuclear Smad3–YAP–TEAD2 complex. This trimeric complex induces the expression of collagen I, connective tissue growth factor, and cyclin D1. Importantly, pharmacologic inhibition of YAP/TEAD interaction with verteporfin blocks stromal hyperplasia and corneal fibrosis by suppressing the expression of fibrotic and cell cycle genes, which lead to restoration of corneal transparency in Smad2-neural crest-deficient mice. Our findings reveal a unique convergence of YAP/TEAD and TGF-β/Smad3 signaling that can be targeted with verteporfin to prevent corneal scarring and blindness. Full article

Bullous keratopathy may lead to severe corneal opacity and impaired visualization of anterior segment structures, complicating surgical qualification for endothelial keratoplasty (EK). We report the case of a 67-year-old male with pseudophakic bullous keratopathy and Fuchs endothelial dystrophy presenting with clinically complete corneal opacity and visual acuity limited to hand motion. Slit-lamp examination and anterior segment optical coherence tomography demonstrated marked epithelial remodeling with a dense plaque-like surface lesion obscuring deeper corneal structures. A staged intraoperative approach was undertaken. Following mechanical epithelial debridement, partial restoration of corneal transparency allowed for an intraoperative reassessment of stromal clarity and subsequent Descemet Stripping Automated Endothelial Keratoplasty (DSAEK). Histopathological examination demonstrated reactive epithelial thickening with associated subepithelial fibrosis consistent with chronic bullous keratopathy. Postoperatively, corneal transparency was restored and best-corrected visual acuity improved to 0.7 Snellen (0.15 logMAR), remaining stable during follow-up without graft-related complications or recurrent epithelial abnormalities. This case highlights the importance of considering epithelial contributions to apparent corneal opacity in advanced bullous keratopathy and suggests that staged intraoperative reassessment may support individualized surgical decision-making in selected patients with inconclusive preoperative evaluation. Full article

Lipid keratopathy is an uncommon corneal disorder characterized by stromal lipid deposition that may cause progressive corneal opacity and visual impairment. We report a case of advanced bilateral lipid keratopathy with severe visual-axis involvement. At presentation, best-corrected visual acuity (BCVA) was counting fingers in the right eye and 0.1 Snellen (1.0 logMAR) in the left eye. Slit-lamp examination and anterior segment optical coherence tomography (AS-OCT) demonstrated dense stromal lipid deposits involving the visual axis in both eyes. The patient underwent staged bilateral penetrating keratoplasty, with procedures performed three months apart. Postoperatively, corneal transparency improved in both eyes. At 6 months, BCVA was 0.5 Snellen (0.3 logMAR) in the right eye and 0.7 Snellen (0.15 logMAR) in the left eye. Residual visual limitation was attributed mainly to coexisting cataract, and sequential cataract surgery was planned. Together, the clinical photographs and AS-OCT scans illustrate an uncommon presentation of visually disabling bilateral lipid keratopathy, characterized by dense central stromal lipid deposition involving both visual axes and profound preoperative visual loss. The case is clinically noteworthy because it combines severe bilateral disease, close clinical–tomographic correlation, and sequential penetrating keratoplasty performed as a staged visual rehabilitation strategy, resulting in restoration of graft clarity and meaningful visual improvement during postoperative follow-up. Full article

Corneal alkali burns represent one of the most severe forms of ocular surface injury and frequently result in persistent inflammation, corneal neovascularization, stromal remodeling, and permanent visual impairment. Current therapeutic approaches incompletely control the inflammatory mechanisms that sustain pathological angiogenesis and tissue disorganization. In this study, we evaluated the effects of a transglutaminase-binding fusion protein (FP) in a rat model of alkali-induced corneal injury. Following standardized alkali burns, animals were treated topically with FP, secretory leukocyte protease inhibitor (SLPI), or Buffer. Corneal epithelial healing, opacity, and neovascularization were assessed clinically and by digital image-based quantification, while histological and immunofluorescence analyses were used to evaluate stromal organization and vascular invasion. Molecular mechanisms were investigated by RT-qPCR and Western blot analysis of key inflammatory, angiogenic, and signaling mediators. FP treatment significantly accelerated corneal re-epithelialization, reduced corneal opacity, and markedly attenuated corneal neovascularization compared to SLPI and Buffer controls. These effects were associated with coordinated downregulation of pro-inflammatory cytokines and angiogenic mediators, including TNF-α, IL-17, VEGF, and cPLA₂. Notably, FP suppressed transglutaminase 2 expression and induced early and sustained downregulation of NF-κB pathway components, identifying modulation of an upstream inflammatory pathway central to corneal angiogenesis and stromal remodeling. Collectively, these findings demonstrate that FP effectively limits inflammation-driven corneal neovascularization and tissue remodeling following alkali injury, supporting its potential as a disease-modifying therapeutic strategy for inflammatory ocular surface disorders. Full article

Corneal fibrosis, clinically referred to as corneal scarring, disrupts the normal architecture and transparency of the cornea and remains a major cause of visual impairment worldwide. Although corneal transplantation can restore vision, its effectiveness is constrained by limited accessibility, donor tissue shortages, and the risk of allograft rejection. Treatments with human corneal stromal stem cells (hCSSCs) have demonstrated scarless healing in preclinical models of acute corneal injury. Here, we report that hCSSCs also modulated pre-existing corneal opacities. We established a reproducible in vivo model of chronic corneal opacity. Given that scar severity varies among corneas even after identical injuries, we developed a non-invasive, image-based method to quantify opacity volume longitudinally in individual corneas. Using this approach, we evaluated the scar-reducing potential of three hCSSC batches previously shown to inhibit acute scarring. Following cell treatment, the pre-existing opacity volumes gradually decreased. In vitro, hCSSCs exposed to pro-inflammatory stimulus exhibited increased metalloproteinase (MMP) activity relative to tissue inhibitor of metalloproteinase (TIMP), as indicated by an elevated MMP2/TIMP2 ratio. This shift may promote matrix remodeling and scar resolution. Overall, our findings provide proof-of-concept for hCSSC-based therapy as a strategy to reduce established corneal scarring and restore corneal transparency. Full article

Irreversible anterior segment blindness with preserved retinal integrity (e.g., dense corneal opacity) remains a major clinical challenge because effective sight-restoring options are limited. Here, we describe an intraocular micro-light-emitting diode (Micro-LED) epiretinal microdisplay intended to deliver patterned optical stimulation to intact photoreceptors by bypassing opaque anterior optics. The prototype was based on a color-capable VGA microdisplay (640 × 480 pixels) and operated at <30 mW under typical conditions. An ultra-thin flexible cable and a copper-mesh–reinforced polydimethylsiloxane (PDMS) encapsulation provided a compact, conformable intraocular package with high pixel density. We evaluated a monochromatic (green) prototype in a single beagle eye $(n=1)$ using a transscleral implantation approach and performed 7 days of postoperative follow-up with slit-lamp examination and multimodal imaging. Patterned stimulation via the implanted display elicited flash-evoked visual evoked potentials (VEPs) with consistent within-session waveform morphology, providing preliminary neurophysiological surrogate evidence of upstream visual pathway activation under the tested conditions in this single-animal pilot. The short-term postoperative course included transient hypotony and anterior segment inflammation, and implant rotation with associated inferior retinal detachment was observed by day 7, highlighting current biomechanical limitations. Beyond anterior segment opacity, the same intraocular optical interface could be explored as a modular light-delivery platform to pair with emerging retinal therapies (e.g., optogenetics), pending chronic safety and functional validation. This pilot large-animal study therefore provides a translationally relevant testbed while delineating key engineering constraints that must be addressed next. Full article

Canine visceral leishmaniasis (CVL), caused by Leishmania infantum, is a multisystemic disease in which ocular involvement is frequent but often underestimated. This study aimed to comprehensively evaluate the clinical, ophthalmological, parasitological, hematological, biochemical, and histopathological alterations in dogs naturally infected with L. infantum from an endemic area of northeastern Brazil, with special emphasis on the relationship between ocular manifestations and systemic disease. Twenty-five symptomatic dogs were evaluated through clinical and ophthalmological examinations, parasitological culture, PCR, laboratory analyses, and histopathology of ocular and periocular tissues. Ocular alterations were observed in 80% of the animals, predominantly bilateral and frequently associated with multiple concurrent lesions, including ocular discharge, conjunctivitis, blepharitis, uveitis, and corneal opacity. Functional ophthalmological tests revealed keratoconjunctivitis sicca and corneal ulcers in a substantial proportion of dogs. Hematological abnormalities were highly prevalent, particularly anemia and thrombocytopenia. Comparative analysis demonstrated that dogs with ocular involvement exhibited significantly higher leukocyte counts and segmented neutrophils, as well as increased AST levels, indicating an enhanced systemic inflammatory response. Histopathological examination revealed intense plasmacytic inflammatory infiltrates and the presence of amastigote forms in ocular and periocular tissues, indicating that both immune-mediated and parasite-driven mechanisms could be involved in disease pathogenesis. Collectively, these findings underscore ocular involvement as a clinically relevant manifestation of CVL and reinforce the importance of routine ophthalmological evaluation in clinical management. Full article

Background: Herpes simplex keratitis (HSK), caused by herpes simplex virus type 1 (HSV-1), is a major cause of infectious blindness. Macrophages are key antiviral effector cells, yet the metabolic mechanisms driving their protective responses remain poorly defined. This study aimed to determine whether interleukin-33 (IL-33) modulates macrophage metabolism and function to enhance antiviral protection in HSK. Methods: Bone marrow-derived macrophages (BMDMs) were stimulated with IL-33, followed by phenotypic and functional characterization using qRT-PCR, flow cytometry, and immunofluorescence. Integrated transcriptomic and non-targeted LC-MS metabolomic profiling was performed to uncover regulatory pathways. For in vivo validation, differently treated BMDMs were adoptively transferred subconjunctivally into a mouse HSK model. Clinical scoring, fluorescein staining, TCID₅₀ quantification of tear samples, and corneal viral gene detection were used to evaluate disease severity and viral burden. Results: IL-33 stimulation increased CD169 and MHC-II expression, expanded the CD169⁺ macrophage subset, and suppressed HSV-1 replication in vitro. Multi-omics integration identified 616 differentially expressed genes and 417 differentially expressed metabolites, revealing substantial remodeling of lipid and amino acid metabolism and suggesting a critical IL-33–lipoprotein lipase (LPL)–palmitoylcarnitine (L-PC) metabolic axis. In vivo, prophylactic adoptive transfer of IL-33-treated BMDMs significantly reduced corneal opacity, epithelial injury, tear viral titers, and virogene expression. LPL inhibition eliminated these benefits, whereas L-PC supplementation partially restored antiviral and clinical improvements. Conclusions: IL-33 reprograms macrophages toward a CD169⁺ antiviral phenotype through an LPL-dependent metabolic pathway, establishing an LPL–L-PC axis essential for enhanced antiviral function and protection against HSK. These findings highlight metabolic tuning of macrophages as a potential preventive immunomodulatory approach for HSV-1-induced ocular disease. Full article

Peters-Plus syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in the B3GLCT gene and characterized by multisystem involvement. Fewer than 100 cases have been reported to date, and only a limited number have been diagnosed prenatally. Prenatal identification is challenging due to the variable and non-specific nature of fetal findings and the frequent absence of detectable ocular anomalies during routine ultrasound. We report a prenatal diagnosis of Peters-Plus syndrome in a monochorionic diamniotic twin pregnancy, based on the progressive identification of early-onset intrauterine growth restriction, rhizomelic limb shortening, craniofacial dysmorphism, and mild central nervous system abnormalities. Standard cytogenetic and chromosomal microarray analyses were normal, prompting extended genetic testing. Prenatal exome sequencing identified a homozygous pathogenic splice-site variant (c.660+1G>A) in B3GLCT in both fetuses, confirming the diagnosis. This case highlights the importance of recognizing suggestive multisystem prenatal findings and the crucial role of advanced genetic testing in achieving an accurate prenatal diagnosis. Early molecular confirmation enables appropriate parental counseling regarding prognosis, recurrence risk, and future reproductive options. Full article

Background and Objectives: Corneal opacity is the fifth global cause of blindness and moderate-to-severe visual impairment due to scar tissue formation. The purpose of this study is to provide an integrated overview of the current state of corneal engineering strategies focused on the comparison with healthy corneas. It aims to identify engineering strategies that would result in functional corneas, providing real alternatives to donor corneal transplants. Materials and Methods: systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and according to the protocol with the ID: CRD420250654641 at the PROSPERO database. The focus question, prompted by considering the shortage of human corneal grafts, was: what is the performance of bioengineered corneal grafts in experimental animal models when compared with healthy eyes in the restoration of corneal anatomy and function? Results: Incorporating human corneal epithelial cells w/ or w/o human corneal stromal stem cells into a gelatin methacrylate and polyethylene glycol diacrylate matrix emerges as the leading option for epithelial layer regeneration. Human and bovine decellularized corneas, porcine corneal ECM in Gelatin methacrylate, dual layered collagen vitrigel and tissue-engineered human anterior hemi-corneas have shown promise for simultaneous regeneration of the corneal stromal and epithelial layers. Corneal stromal tissue regeneration could be positively impacted by transplantation with grafts derived from aligned self-lifting analogous tissue equivalents and collagen-based hydrogels. Finally, scaffolds of silk fibroin and human purified type I collagen represent promising approaches for corneal endothelial regeneration, though their effectiveness is contingent upon integration with endothelial cells. Conclusions: Collectively, these findings contribute to the growing body of evidence supporting the potential of tissue-engineered corneal substitutes as viable therapeutic options for corneal blindness and vision impairment. Assessing the optical and functional properties of the regenerated cornea should be a cornerstone in all studies aiming to evaluate their clinical effectiveness. Full article

Intraoperative optical coherence tomography (iOCT) has emerged as a pivotal technology in anterior segment surgery, particularly in cases limited by corneal opacity, edema, or altered anatomy. By providing real-time, cross-sectional imaging, iOCT enables surgeons to visualize otherwise hidden structures and to perform critical intraocular maneuvers with greater precision and safety. Its integration into the surgical microscope allows continuous monitoring of tissue–instrument interaction, transforming traditionally “blind” procedures into image-guided interventions. This review highlights the role of iOCT in endothelial keratoplasty, deep anterior lamellar keratoplasty (DALK), management of acute corneal hydrops, synechiolysis, glaucoma drainage device implantation, and ocular trauma. In endothelial procedures, iOCT helps confirm Descemet membrane removal, graft orientation, and resolution of interface fluid. In DALK, it facilitates accurate cannula placement, stromal depth assessment, and evaluation of leucoma extension to guide surgical strategy. During hydrops management, iOCT supports precise air/gas injection and compression suture placement. Additionally, it enhances safety in synechiolysis, shunt implantation, and repair of traumatic corneal injuries. Full article

Cuban sugarcane wax alcohol (policosanol) is a blend of eight characteristic aliphatic alcohols extracted from the Cuban sugarcane and widely recognized for its multifunctional applications and therapeutic properties. In the present study, the potency of policosanol (POL) was assessed for its ability to prevent metabolic stress and associated disorders posed by a high-cholesterol (HC) and high-galactose (HG) diet in zebrafish (Danio rerio). Adult zebrafish (n = 56/group) were fed either with an HC+HG diet (containing 4%, w/w cholesterol and 30%, w/w galactose), or an HC+HG amalgamated diet with POL (final 0.1% w/w or 0.5% w/w). Zebrafish in the specified groups were sacrificed post-30 weeks of feeding, and blood and organs (liver, brain, and eyes) were processed for biochemical, histological, and immunohistochemical (IHC) analysis. After 30 weeks of feeding, the highest mortality (12.5%) was noticed in the HC+HG supplement group, which was reduced to 4.5% with co-supplementation of POL (0.1% and 0.5%). In a dose-dependent manner, POL significantly reversed HC+HG elevated levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), glucose, and malondialdehyde (MDA), while substantially augmenting plasma high-density lipoprotein cholesterol (HDL-C), sulfhydryl content, ferric ion reduction ability (FRA), and paraoxonase (PON) activity. In addition, POL mitigated HC+HG-induced hepatomegaly, inflammation, and fatty liver changes. Consistently, POL minimizes ROS generation and cellular senescence in the brain and substantially improves HC+HG-induced cognitive changes (cessation of swimming ability and motion), with a marked ~5 times higher swimming distance. Notably, POL mitigated the HC+HG-induced corneal opacity and attenuated oxidative stress, apoptosis, 4-hydroxynonenal (4-HNE) accumulation, and myelin sheath degeneration in the retina. The findings underscore the therapeutic potential of policosanol in attenuating oxidative stress, metabolic changes, and various organ damage caused by prolonged exposure to the HC+HG diet. Full article

A herd of approximately 300 Spanish meat goats in central Alabama experienced sporadic ocular, respiratory, and reproductive diseases over two years, prompting diagnostic investigation at Auburn University’s JT Vaughan Large Animal Teaching Hospital. Five representative doelings exhibiting ocular lesions were examined. Clinical signs included conjunctivitis, corneal opacity, uveitis, and, in one severe case, systemic illness. Initial treatment with topical and systemic antibiotics provided incomplete resolution, raising suspicion of infectious keratoconjunctivitis of atypical etiology. Comprehensive diagnostic testing was performed, including aerobic and Mycoplasma cultures, Giemsa staining, and molecular assays. Moraxella bovoculi was cultured; however, Giemsa staining revealed Chlamydia elementary bodies, and a FRET-qPCR with DNA sequencing confirmed high Chlamydia pecorum loads (up to 1.1 × 10⁷ copies/swab). Mycoplasma testing was negative. Extended treatment with systemic and topical oxytetracycline led to gradual clinical improvement, with C. pecorum DNA declining over 22,000-fold and becoming undetectable after five weeks. This case represents the first documented report of C. pecorum–associated keratoconjunctivitis in goats in the United States. The findings underscore the diagnostic importance of molecular assays for detecting intracellular pathogens that may be missed by culture. The protracted treatment course highlights the therapeutic challenges posed by chlamydial infections due to their intracellular persistence. Additionally, the concurrent detection of M. bovoculi suggests the potential for mixed infections influencing disease severity. These results emphasize C. pecorum as an emerging pathogen of caprine ocular disease with implications for herd health and management. Full article

Cataracts cause vision loss in rabbits, often either spontaneously or as secondary to uveitis. This study considers the ophthalmic presentation, treatment, and outcome of phacoemulsification in seven pet rabbits: six presenting with lens cloudiness and one presenting with a white mass in the iris. Ophthalmic examinations revealed cataracts. The treatment plan was phacoemulsification. Encephalitozoon cuniculi was identified via an enzyme-linked immunosorbent assay technique performed on all rabbits. Ocular ultrasonography was performed to rule out retinal detachment. Phacoemulsification using the one-handed technique without intraocular lens implantation was performed in 8 of the eyes of the 7 rabbits. After surgery, the corneal wounds healed within 2 weeks. All rabbits were comfortable with opening their eyes and had a positive dazzle reflex and a clear visual axis, with no other severe complications (such as retinal detachment, intraocular hemorrhaging, or uncontrolled glaucoma) throughout the post-operative period. Postoperative complications consisted of corneal edema around the surgical wound (2 eyes; 25%); partial anterior synechiae (1 eye; 12.5%); partial posterior synechiae (5 eyes; 3 eyes before surgery and 2 eyes after surgery; 25%); posterior capsular opacities (3 eyes; 37.5%); and lens fiber overgrowths (2 eyes; 25%). In conclusion, successful phacoemulsification was achieved in the seven pet rabbits. Full article

To describe a technique for managing acute corneal hydrops in eyes with keratoconus using dome stromal drainage with intracameral air injection under real-time three-dimensional (3D) microscope-integrated optical coherence tomography (OCT) guidance. We describe a retrospective case series of six eyes from six patients with keratoconus who developed acute corneal hydrops. All eyes underwent intracameral air injection with controlled dome puncture for stromal fluid drainage, without the use of sutures. The procedure was performed using a 3D visualization system that enables integrated and simultaneous viewing of the surgical field and intraoperative OCT scan (a 3D digitally assisted visualization system that displayed a split-screen view of the surgical field and OCT cross-sections simultaneously). Postoperative resolution of edema and improvement in clarity were documented. The resolution of corneal edema allowed for subsequent mushroom-shaped penetrating keratoplasty performed with a femtosecond laser in four eyes of four patients. All six eyes showed significant resolution of corneal edema within 2 to 4 weeks. Stromal clefts collapsed rapidly after drainage. In each case, the thick edema was reduced to a confined leucoma. No intraoperative or postoperative complications were observed. All four eyes that underwent a femtosecond laser-assisted mushroom-shaped penetrating keratoplasty showed optimal anatomical and functional success. Air-assisted dome drainage, combined with simultaneous 3D and OCT visualization, is a safe and effective technique for treating acute corneal hydrops. This technology enables real-time decision-making and enhances surgical precision, opening the door to advanced procedures that are otherwise limited by corneal opacity. Full article