Corneal Tissue Research Articles

Far-Ultraviolet C Disinfection Reduces Oxidative Damage to the Cornea Compared to Povidone-Iodine Disinfection

Far-ultraviolet C (far-UVC) light shows promise for pathogen control but its safety and efficacy for corneal disinfection remain unclear. In this study, safe far-UVC dosages were investigated for corneal disinfection and its germicidal performance and oxidative damage potential to 5% povidone-iodine (PVP-I) were compared. Rat corneas were exposed to varying 222 nm far-UVC doses (3–60 mJ/cm2) and assessed for ocular damage, apoptosis, and oxidative stress to determine the safe dose of far-UVC. Far-UVC at 30 mJ/cm2 induced corneal apoptosis and oxidative damage, but 15 mJ/cm2 caused no apoptosis or oxidative damage. At this optimized dose (9 mJ/cm2), far-UVC achieved 90.5% sterilization, exceeding 5% PVP-I (80.8%), with significantly less oxidative damage and cell death in the cornea. In conclusion, our study demonstrates that the use of 5% povidone-iodine (PVP-I) for disinfection results in significant oxidative damage to the corneal tissue. However, a safe dosage of far-UVC light exhibited a promising disinfection effect without causing oxidative damage to the corneal tissue. Far-UVC offers a promising alternative for corneal disinfection but requires careful dosage control (≤30 mJ/cm2) to avoid ocular surface harm.

Advancements in Hydrogels for Corneal Healing and Tissue Engineering.

Hydrogels have garnered significant attention for their versatile applications across various fields, including biomedical engineering. This review delves into the fundamentals of hydrogels, exploring their definition, properties, and classification. Hydrogels, as three-dimensional networks of crosslinked polymers, possess tunable properties such as biocompatibility, mechanical strength, and hydrophilicity, making them ideal for medical applications. Uniquely, this article offers original insights into the application of hydrogels specifically for corneal tissue engineering, bridging a gap in current research. The review further examines the anatomical and functional complexities of the cornea, highlighting the challenges associated with corneal pathologies and the current reliance on donor corneas for transplantation. Considering the global shortage of donor corneas, this review discusses the potential of hydrogel-based materials in corneal tissue engineering. Emphasis is placed on the synthesis processes, including physical and chemical crosslinking, and the integration of bioactive molecules. Stimuli-responsive hydrogels, which react to environmental triggers, are identified as promising tools for drug delivery and tissue repair. Additionally, clinical applications of hydrogels in corneal pathologies are explored, showcasing their efficacy in various trials. Finally, the review addresses the challenges of regulatory approval and the need for further research to fully realize the potential of hydrogels in corneal tissue engineering, offering a promising outlook for future developments in this field.

Outcomes of sclerokeratoplasty in severe ocular surface disease

Sclerocorneal grafts are procedures considered in cases with extensive corneal and scleral tissue destruction. The study aims to describe sclerokeratoplasty outcomes in severely diseased eyes. We performed a retrospective review of clinical records. Demographic characteristics, medical history, surgical indications, aetiology of perforation, visual outcomes, complications associated with the surgical procedure, and ocular integrity at the end of the follow-up were obtained. Wilcoxon-signed rank tests and Mann-Whitney tests were used to compare complications between groups and outcomes at final follow-up. Survival analysis was performed to analyse vision preservation and global integrity and presented in Kaplan-Meier curves. 40 eyes from 40 patients with a mean age of 48.83 ± 18.85 years and a mean follow-up of 21.13 ± 33.92 months were included in the study. Median corrected visual acuity before and after the procedure remained at 2.8 logMAR. Twenty-seven eyes presented complications. The most common complications were a persistent epithelial defect in 11, hypertension in 10, and perforation in 8 eyes. More than half of the eyes (67.5%) presented with either one or more of all complications after corneoscleral graft. No significant differences were found regarding age, gender, or DM history. Concerning perforation, a significant difference was found between infectious and non-infectious only in the presentation of ocular hypertension (p = 0.048). Vision was preserved in 72.5% of the eyes, with a median survival probability of 4.12 years. Preservation of the ocular integrity was achieved in 85% of the eyes, with a median survival probability of 12 years. Sclerokeratoplasty despite being challenging and technically demanding followed by defiant complications, in some situations such as infectious keratitis and autoimmune diseases, is likely a procedure that salvages the eye and preserves vision.

Advancements in Polymer Biomaterials as Scaffolds for Corneal Endothelium Tissue Engineering

Corneal endothelial dysfunction is a leading cause of vision loss globally, frequently requiring corneal transplantation. However, the limited availability of donor tissues, particularly in developing countries, has spurred on the exploration of tissue engineering strategies, with a focus on polymer biomaterials as scaffolds for corneal endotlhelium regeneration. This review provides a comprehensive overview of the advancements in polymer biomaterials, focusing on their role in supporting the growth, differentiation, and functional maintenance of human corneal endothelial cells (CECs). Key properties of scaffold materials, including optical clarity, biocompatibility, biodegradability, mechanical stability, permeability, and surface wettability, are discussed in detail. The review also explores the latest innovations in micro- and nano-topological morphologies, fabrication techniques such as electrospinning and 3D/4D bioprinting, and the integration of drug delivery systems into scaffolds. Despite significant progress, challenges remain in translating these technologies to clinical applications. Future directions for research are highlighted, including the need for improved biomaterial combinations, a deeper understanding of CEC biology, and the development of scalable manufacturing processes. This review aims to serve as a resource for researchers and clinician–scientists seeking to advance the field of corneal endothelium tissue engineering.

Mechanical properties of stromal striae, and their impact on corneal tissue behavior

Cornea is an essential element of our eye. The refractive power of the cornea is closely related to its shape, which depends on the balance between its mechanical properties and the intraocular pressure. However, in keratoconus, the shape of the cornea is altered, and the mechanical properties (i.e., elastic modulus and viscosity) are reduced. These alterations have been associated with the development of striae within the cornea. Recently, such striae have been observed in healthy corneas as well, but with slightly different shapes. Our study investigated the mechanical role of these striae. To this end, we performed an inflation test under Optical Coherence Tomography: tomographic volumes were acquired in the central zone of eleven human corneas during an inflation test. Striae planes were extracted from the segmented images, and principal deformation maps were obtained by Digital Volume Correlation (DVC). We observe that the pattern of the striae does not change with pressure, even far above physiological pressure. Maximum principal strains are co-localized with the striae and are oriented perpendicular to the striae. We also observe that principal deformations on the striae increase with depth in the cornea. Our results show that striae lead to greater deformability in the direction perpendicular to the striae, especially in the posterior part of the cornea where they are the most visible. This supports the idea that the striae are undulations in the cornea collagenous microstructure, which are progressively unfolded under loading. They decrease the global stiffness of the cornea, in particular in the posterior part, and thus may help in accommodating deformations.

Effects of Eye Bank Donor Age Expansion on Corneal Endothelial Cell Density and Surgeon Tissue Acceptance

Effects of Eye Bank Donor Age Expansion on Corneal Endothelial Cell Density and Surgeon Tissue Acceptance

Multiphoton scaling of femtosecond laser-induced refractive index change (LIRIC) in hydrogels and rabbit cornea

To find optimal conditions for performing laser induced refractive index change (LIRIC) in living eyes with both safety and efficacy, we investigated multiphoton excitation scaling of this procedure in hydrogel and excised corneal tissue. Three distinct wavelength modalities were examined: high-repetition-rate (HRR) and low-repetition-rate (LRR) 405 nm systems, as well as 800 nm and 1035 nm systems, whose LIRIC-inducing properties are described for the first time. Of all the systems, LRR 405 nm-LIRIC was able to produce the highest phase shifts at the lowest average laser powers. Relative merits and drawbacks to each modality are discussed as they relate to future efforts towards LIRIC-based refractive error correction in humans.

Tissue engineering of Cornea via Type 1 Collagen Biomaterials – A perspective

Engineering corneal tissue has advanced significantly in recent years. Engineering a biocompatible, mechanically stable, and optically clear tissue presents significant engineering hurdles. Two fundamental strategies have been explored by scholars to address these issues: cell-based methods for controlling cells their own extracellular matrix and scaffold-based methods for supplying dense, transparent matrices for cell growth. Both approaches have had some level of success. Additionally, new developments in innervating a tissue-engineered construct have been developed. Future research must concentrate on enhancing the mechanical stability of engineered constructions and the host reaction to implantation. Type 1 Collagen Biomaterial has been used for the construction of scaffolds or implantation for the cornea repair. Various methods for fabrication of the scaffolds have been described and mentioned tissue engineering application for cornea repair and regeneration. Given this correspondence, the type 1 collagen was a potential biomaterial for tissue engineering scaffold fabrication for effective regeneration of cornea.

Fabrication and characterization of an electrospun silk fibroin/gelatin transparent graft material for corneal epithelial regeneration

The damaged corneal epithelial causing loss of vision can be restored by epithelial tissue regeneration through tissue engineering approach that provides an engineered corneal substitute with appropriate properties and nanofibrous architecture. This works reports a polymeric matrix that was derived from silk fibroin (SF) and gelatin (GE) natural polymer blend with optimized composition resembling the structure and function of the native epithelial tissue. SF/GE blend spinning solutions prepared with different volume ratios of SF/GE: 70/30, 50/50, and 30/70 were used to fabricate electrospun mats. The fabricated two-dimensional mats had nanofibrous porous architecture having interconnected pores with pore size range of 175–267 nm suitable for corneal epithelial regeneration and 891.2–558 nm fiber diameter range as revealed by scanning electron microscopic image analysis. The performed Fourier transform infrared spectra confirmed the presence of individual polymers in the scaffolds and the scaffolds are hydrophilic in nature. Among the scaffolds, SF/GE 70:30 and SF/GE 50:50 composition possess desired porosity range of 87–88%. The tensile strength was slightly decreased with increase in GE content and the strength obtained was in the range 2.74–2.26 Mpa. An enhanced transparency was obtained with increased GE concentration, the transparency range of 73–82% observed with SF/GE:50/50 matches with the transparency of natural corneal epithelium. The biocompatibility of the scaffolds was confirmed by cell attachment, cytotoxicity and ROS evaluation by culturing rabbit corneal fibroblast cells (SIRC) on the scaffolds. Among the scaffolds, SF/GE: 70/30 exhibited the highest cell viability, but with less transparency ranging 55–71%. Therefore, considering all the properties, SF/GE with 50:50 ratio scaffold may be a suitable substrate in the field of corneal tissue engineering.

304 (PB292): Effects of Nectin-4 targeted Bicycle Toxin Conjugate, zelenectide pevedotin (BT8009), and enfortumab vedotin on a human corneal tissue model

304 (PB292): Effects of Nectin-4 targeted Bicycle Toxin Conjugate, zelenectide pevedotin (BT8009), and enfortumab vedotin on a human corneal tissue model

Bufalin Regulates STAT3 Signaling Pathway to Inhibit Corneal Neovascularization and Fibrosis After Alkali Burn in Rats

Purpose Bufalin (BU) is a bioactive ingredient extracted from the skin and parotid venom glands of Bufo raddei, which can effectively inhibit angiogenesis. The aim of this study was to investigate whether BU could affect corneal neovascularization (CoNV). Methods A rat CoNV model (right eye) was constructed by administration of NaOH, and the left eye served as a control. Corneal damage scores of rats were detected. Hematoxylin & eosin, TUNEL, and Masson staining examined pathological changes, apoptosis, and fibrosis of corneal tissues. Immunohistochemistry and western blotting assessed the expression of proteins. Results BU intervention resulted in a significant reduction in corneal inflammatory cells, repair of corneal epithelial hyperplasia, significant reduction in stromal edema, and reduction in vascular proliferation. BU can inhibit corneal neovascularization. Conclusion This study demonstrated that BU inhibits CoNV, fibrosis, and inflammation by modulating the STAT3 signaling pathway, elucidating the intrinsic mechanism of its protective effect. BU has great potential in the treatment of CoNV caused by corneal alkali burns.

MUC1‑ND interacts with TRPV1 to promote corneal epithelial cell proliferation in diabetic dry eye mice by partly activating the AKT signaling pathway.

Although both mucin1 (MUC1) and transient receptor potential cation channel subfamily V member 1 (TRPV1) have been reported to be associated with dry eye (DE) disease, whether they interact and their regulatory roles in diabetic DE disease are unknown. Diabetic DE model mice were generated by streptozotocin induction and assessed by corneal fluorescein staining, tear ferning (TF) tests, phenol red thread tests, hematoxylin and eosin staining of corneal sections and periodic acid Schiff staining of conjunctival sections. Cell proliferation was measured by CCK8 assay. Western blotting was performed to measure protein expression. Primary mouse corneal epithelial cells (MCECs) were cultured after enzymatic digestion. Immunofluorescence staining of MCECs and frozen corneal sections was conducted to assess protein expression and colocalization. Coimmunoprecipitation was performed to detect protein‑protein interactions. It was found that, compared with control mice, diabetic DE mice exhibited increased corneal epithelial defects, reduced tear production, poorer TF pattern grades and impaired corneal and conjunctival tissues. In vivo and in vitro experiments showed that hyperglycemia impaired cell proliferation, accompanied by decreased levels of the MUC1 extracellular domain (MUC1‑ND) and TRPV1. Additionally, it was found that capsazepine (a TRPV1 antagonist) inhibited the proliferation of MCECs. Notably, MUC1‑ND was shown to interact with the TRPV1 protein in the control group but not in the diabetic DE group. It was also found that the AKT signaling pathway was attenuated in the diabetic DE mice and downstream of TRPV1. MUC1‑ND interacted with TRPV1, partly activating the AKT signaling pathway to promote MCEC proliferation. The present study found that the interaction of MUC1‑ND with TRPV1 promotes MCEC proliferation by partly activating the AKT signaling pathway, providing new insight into the pathogenesis of corneal epithelial dysfunction in diabetic DE disease.

Bio-spectroscopic analysis of corneal structural alterations in dry eye disease: A study of collagen, co-enzymes, lipids, and proteins with emphasis on phytotherapy intervention

Dry eye disease (DED) stands as a prevalent cause for ophthalmology consultations, securing the third position following refractive errors and cataracts. Moreover, the likelihood of experiencing DED escalates with advancing age. In this experimental study corneal tissue alterations due to DED were investigated over different periods by applying both infrared and synchronous fluorescence spectroscopy. The potential effects of instillation of pomegranate and green tea water extracts as green-friendly treatment modalities were also evaluated. The obtained results collectively indicate that DED affects the OH bearing constituents (collagen, glycosaminoglycans, and proteoglycans) of cornea leading to changes in protein secondary structure and the collagen fibrils. Additionally, enhanced dehydrated environment, and reduced energetic/metabolic state, as indicated by co-enzymes, was observed. Phyto-therapeutic administration can contain these alterations with enhanced energetic/metabolic state and increased hydration environment. In conclusion, instillation of green tea extract can protect/restore the collagen fibrils and its potential effects, in general, exceeds that of pomegranate extract.

Antibacterial and cytocompatible silver coating for titanium Boston Keratoprosthesis.

The Boston Keratoprosthesis (BKPro) serves as a medical solution for restoring vision in complex cases of corneal blindness. Comprising a front plate made of polymethylmethacrylate (PMMA) and a back plate of titanium (Ti), this device utilizes the beneficial biomaterial properties of Ti. While BKPro demonstrates promising retention rates, infection emerges as a significant concern that impacts its long-term efficacy. However, limited research exists on enhancement of BKPros through intrinsic infection-preventing mechanisms. In this regard, metal ions, especially the well-known Ag+ ions, are a promising alternative to obtain implants with innate antibacterial properties. However, little information is available about the effects of Ag in corneal tissue, especially within human corneal keratocytes (HCKs). In this work, an electrodeposition treatment using a constant pulse is proposed to attach Ag complexes onto rough Ti surfaces, thus providing antibacterial properties without inducing cytotoxicity. Complete physicochemical characterization and ion release studies were carried out with both control and Ag-treated samples. The possible cytotoxic effects in the short and long term were evaluated in vitro with HCKs. Moreover, the antibacterial properties of the silver-treated surfaces were tested against the gram-negative bacterial strain Pseudomonas aeruginosa and the gram-positive strain Staphylococcus epidermidis, that are common contributors to infections in BKPros. Physicochemical characterization confirmed the presence of silver, predominantly in oxide form, with low release of Ag+ ions. Ag-treated surfaces demonstrated no cytotoxicity and promoted long-term proliferation of HCKs. Furthermore, the silver-treated surfaces exhibited a potent antibacterial effect, causing a reduction in bacterial adhesion and evident damage to the bacterial cell walls of P. aeruginosa and S. epidermidis. The low release of Ag+ ions suggested reactive oxygen species (ROS)-mediated oxidative stress imbalance as the bactericidal mechanism of the silver deposits. In conclusion, the proposed electrodeposition technique confers antibacterial protection to the Ti backplate of BKPro, mitigating implant-threatening infections while ensuring non-cytotoxicity within the corneal tissue.

Epidemiological Study and Seropositivity in Viral Panel Testing Among Corneal Tissue Donors.

Corneal tissue is a critical component for vision restoration through transplantation, yet the availability of suitable corneal tissue is limited. This limitation results in long waiting lists and high demand, especially in countries with lower donation rates compared to global benchmarks. In Mexico, the corneal donation rate remains significantly behind other Latin American countries and leading nations such as Spain. Understanding the characteristics of corneal tissue donors is essential for improving donation practices and addressing the shortage of available tissues. This descriptive retrospective study analyzed electronic medical records of cadaveric corneal donors at the General Regional Hospital 1 of the Mexican Social Security Institute of Querétaro from January 2022 to December 2023. Donors were included based on criteria such as age (2-85 years) and known cause of death. Exclusion criteria included age outside the specified range, neoplastic diseases, active systemic infections, and prior ocular surgeries. Serological testing for human immunodeficiency virus (HIV), Venereal Disease Research Laboratory (VDRL), coronavirus disease 2019 (COVID-19), hepatitis B virus (HBV), and hepatitis C virus (HCV was performed to assess viral reactivity. Statistical analyses were conducted usingIBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States), summarizing data with descriptive statistics. The study included 185 corneal donors with a mean age of 56.34 years. The majority were male (109; 58.9%), and the leading causes of death were cardiogenic shock (34; 18.4%), hypovolemic shock (31; 16.8%), and acute respiratory failure (30; 16.2%). Exclusion due to positive serological tests included seven donors (3.8%) for HIV and seven (3.8%) for SARS-CoV-2. A total of 16 donors (8.6%) were excluded due to positive results in the viral serological panel. The most common comorbidities were chronic kidney disease (36; 19.5%), type 2 diabetes mellitus (28; 15.1%), and systemic hypertension (31; 16.8%). The study highlights a predominantly male donor profile with a mean age of 56.34 years and emphasizes cardiogenic shock as a leading cause of death. The notably higher seropositivity rate of 8.6% for various viral infections compared to international reports indicates a need for improved health interventions and screening processes. The focus on cardiovascular and respiratory causes of death underscores regional health issues affecting donation patterns. To address the organ and tissue donation shortfall, it is crucial to enhance coordination within donation teams and increase public awareness, given the significant gap in donation rates compared to leading countries.

Optimizing Corneal Transplant Safety: The Impact of Mandatory Prion Protein Testing on Iatrogenic Creutzfeldt-Jakob Disease Prevention in the Czech Republic.

The purpose of this study was to assess the effectiveness of legally mandated testing for pathogenic prion proteins in corneal tissue donors in the Czech Republic, considering its impact on safety, financial, and temporal costs. Between January 2007 and December 2023, standardized brain regions were collected from all corneal tissue donors in the Czech Republic. Tissue samples were tested for the presence of pathogenic prion proteins by the Czech Reference Laboratory for Human Prion Diseases. The testing used a Western blot analysis, using 2 distinct monoclonal anti-PrP antibodies. A total of 8030 donors were tested. Four tested samples were initially weakly positive. Subsequent testing conclusively determined these samples to be negative. The remaining 8026 tests yielded negative results confirming the safety of donor screening. We did not observe any cases of proven transmissible spongiform encephalopathies (TSEs). TSE testing has consistently confirmed that no patients with TSE have been selected into the corneal donor pool, solidifying the effectiveness of the active surveillance program and exclusion criteria. We propose that these mechanisms effectively prevent patients with TSEs from being included in the corneal tissue donor pool. However, the substantial financial costs and a 2-day delay in processing pose challenges, contributing to graft nonutilization and potential negative impacts on patients in acute need. Moreover, the unique requirement for pathogenic prion testing in the Czech Republic also makes importing any corneal grafts from other countries impossible, as those tissues do not fulfill Czech legal requirements.

Preparation, physico-biochemical characterization, and proteomic analysis of highly transparent corneal extracellular matrices for lamellar keratoplasty and tissue-engineered cornea construction

Corneal opacity and deformation, which often require corneal transplantation for treatment, are among the leading causes of monocular blindness. To restore corneal clarity and integrity, there is a need for an artificial stroma that not only matches the transparency of donated human cornea but also effectively integrates to the corneal tissue. In this study, a transparent decellularized cornea was successfully developed using the high hydrostatic pressure method with processing conditions optimized for corneal decellularization. Biochemical analyses demonstrated the effective removal of cellular components from the transparent decellularized corneas, while preserving collagen and glycosaminoglycans. Proteome analysis also revealed that core matrisome and matrisome-associated proteins remained following decellularization, similar to the composition observed in untreated corneas. The light transmittance of the transparent decellularized corneas was 86.4 ± 1.5 % in the visible region, comparable to that of donated human corneas. No complications, such as angiogenesis, were observed following interlamellar corneal transplantation in rabbits. The grafts were almost imperceptible immediately following surgery and achieved complete transparency within a few days, becoming indistinguishable even under a microscope. The transparent decellularized cornea presented here has promising potential as a material for application in lamellar keratoplasty.

Revealing regional variations in scleral shear modulus in a rabbit eye model using multi-directional ultrasound optical coherence elastography

The mechanical properties of the sclera play a critical role in supporting the ocular structure and maintaining its shape. However, non-invasive measurements to quantify scleral biomechanics remain challenging. Recently introduced multi-directional optical coherence elastography (OCE) combined with an air-coupled ultrasound transducer for excitation of elastic surface waves was used to estimate phase speed and shear modulus in ex vivo rabbit globes (n = 7). The scleral phase speed (12.1 ± 3.2 m/s) was directional-dependent and higher than for corneal tissue (5.9 ± 1.4 m/s). In the tested locations, the sclera proved to be more anisotropic than the cornea by a factor of 11 in the maximum of modified planar anisotropy coefficient. The scleral shear moduli, estimated using a modified Rayleigh-Lamb wave model, showed significantly higher values in the circumferential direction (65.4 ± 31.9 kPa) than in meridional (22.5 ± 7.2 kPa); and in the anterior zone (27.3 ± 9.3 kPa) than in the posterior zone (17.8 ± 7.4 kPa). The multi-directional scanning approach allowed both quantification and radial mapping of estimated parameters within a single measurement. The results indicate that multi-directional OCE provides a valuable non-invasive assessment of scleral tissue properties that may be useful in the development of improved ocular models, the evaluation of potential myopia treatment strategies, and disease characterization and monitoring.

Customized Corneal Cross-Linking with Microneedle-Mediated Riboflavin Delivery for Keratoconus Treatment.

In this study, a novel customized corneal cross-linking (CXL) treatment is explored that utilizes microneedles (MNs) for targeted riboflavin (RF) administration prior to the CXL procedure. Unlike the conventional "one-size-fits-all" approach, this protocol offers an option for more precise and efficacious treatment. To simulate a customized corneal crosslinking technique, four distinct microneedle (MN) molds designs, including circular, semi-circular, annular and butterfly shaped, are crafted for loading an optimized RF-hyaluronic acid solution and for the subsequent fabrication of MN arrays with varying morphologies. These MNs can gently puncture the corneal epithelium while preserving the integrity of the underlying stromal layer. Following the application of these microneedles, RF solution is replenished to enhance the RF content within the stroma through the punctures created by the MNs, resulting in exceptional customized corneal cross-linking effects that are comparable to the conventional epi-off CXL protocol. Additionally, it flattened the corneal curvature within the treated zone and facilitated rapid postoperative recovery of corneal tissue. These findings suggest that the integration of customized microneedle RF delivery with corneal crosslinking technology represents a potential novel treatment modality, holding promise for the tailored treatment of corneal pathologies, and offering a more precise and efficient alternative to traditional methods.

Color Doppler Imaging, Endothelin-1, Corneal Biomechanics and Scleral Rigidity in Asymmetric Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) presents a multifaceted etiopathogenesis involving ischemic, inflammatory, and genetic components. This study investigates the correlation between ocular hemodynamics, scleral rigidity (SR), and plasma endothelin-1 (ET1) levels in treatment-naive patients with asymmetrical AMD. This study included 20 treatment-naive patients (12 females and 8 males) with an average age of 76.4 ± 3.7 years, who presented with AMD with neovascular membrane formation (nAMD) in one eye, and intermediate grade 2 AMD (iAMD) in the other eye. The control group consisted of 20 healthy subjects (13 females and 7 males) with a mean age of 74.7 ± 3.9 years. All patients and healthy controls underwent color Doppler imaging (i) of the ophthalmic artery (OA), short posterior ciliary arteries (SPCAs), and central retinal artery (CRA); Plasma ET-1 levels were measured for all patients and healthy subjects. Corneal biomechanics were assessed using an Ocular Response Analyzer and two indices were obtained: corneal hysteresis (CH) and corneal resistance factor (CRF). Results showed reduced blood flow velocities and increased resistance indices in AMD eyes, particularly affecting the short posterior ciliary arteries. According to mechanical theory, ARMD eyes exhibited elevated scleral rigidity and corneal resistance factor compared to controls, with a notable rise in SR in neovascular AMD (nAMD) eyes. As per the chronic subacute inflammation theory, plasma ET-1 levels were significantly higher in AMD patients, correlating with abnormal SPCAs blood flow and increased resistance indices. Findings suggest a multifactorial etiology of AMD involving an increase of ET-1 plasma levels with biomechanic damages of corneal and scleral tissue in nAMD.