Smart materials dynamically sense and respond to physiological signals like reactive oxygen species (ROS), pH, and light, surpassing traditional materials such as poly(lactic-co-glycolic acid), which have high drug loss rates and limited spatiotemporal control. These innovative materials offer new strategies for ophthalmic treatments, with core advantages including targeted delivery via ROS-sensitive nanocarriers, precise regulation through microvalves, and multifunctional integration, such as glucose-responsive contact lenses that create a "sensing-treatment" loop. However, challenges remain, like pathological microenvironment interference with material response specificity, and the need to address long-term biocompatibility and energy dependence issues. This article systematically examines three key treatment barriers: the blood-ocular barrier, immune rejection, and physiological fluctuations, while reviewing innovative smart material design strategies. Future research should focus on biomimetic interface engineering, for example, cornea mimicking nanostructures, AI-driven dynamic optimization like causal network-regulated drug release, and multidisciplinary approaches combining gene editing with smart materials. These efforts aim to shift from structural replacement to physiological function simulation, enabling precise treatment of ophthalmic diseases. Clinical translation must balance innovation with safety, prioritizing clinical value to ensure reliable, widespread application of smart materials in ophthalmology.

The scarcity of human donor corneal graft tissue worldwide available for corneal transplantation necessitates the development of alternative therapeutic strategies for treating patients with corneal blindness. Corneal stromal stem cells (CSSCs) have the potential to address this global shortage by allowing a single donor cornea to treat multiple patients. To directly deliver CSSCs to corneal defects within an engineered biomatrix, we developed a UNIversal Orthogonal Network (UNION) collagen bioink that crosslinks in situ with a bioorthogonal, covalent chemistry. This cell-gel therapy is optically transparent, stable against contraction forces exerted by CSSCs, and permissive to the efficient growth of corneal epithelial cells. Furthermore, CSSCs remain viable within the UNION collagen gel precursor solution under standard storage and transportation conditions. This approach promoted corneal transparency and re-epithelialization in a rabbit anterior lamellar keratoplasty model, indicating that the UNION collagen bioink serves effectively as an in situ-forming, suture-free therapy for delivering CSSCs to corneal wounds.

MicroRNAs (miRNAs) are conserved, short, non-coding RNAs that play a crucial role in regulating gene expression. Emerging evidence suggests that miRNAs are closely involved in the pathophysiology of various corneal diseases, particularly in regulating corneal wound healing, inflammation and neovascularization. In this review, we summarized the recent progress of miRNAs in corneal diseases, especially focused on their application as diagnostic biomarkers, regulators of cell biology, and therapeutic targets. Recent advances in miRNA detection technology have made it possible to analyze minimal miRNAs in samples such as tears or exosomes, further enhancing the ability to identify disease-specific miRNA profiles and providing potential objective indicators for the early diagnosis of disease. Meanwhile, we summarized the mechanisms and pathways of multiple miRNAs in regulating various biological processes of corneal cells, as well as the advantages of studying miRNA compared to proteins or genes. Furthermore, we explore the potential of miRNAs-based therapies, especially introduce various miRNA delivery systems and challenges associated with clinical translation. This review highlights the need for further research to harness the full potential of miRNAs in treating various corneal diseases.

Diabetic keratopathy (DK) is a degenerative corneal disease occurring in more than 50 % of diabetic patients. DK is correlated with the hyperglycemic state causing morphological and functional changes in corneal layers. Currently, most studies on the cornea are performed on two-dimensional (2D) cultures in vitro or animal models. Although 2D culture models can provide large amounts of data at low cost, they poorly represent the complex pathophysiology of the human cornea and hardly predict in vivo responses that can be achieved with animal model studies. However, the use of the latter presents ethical problems. Therefore, it is necessary to identify new strategies and models that can integrate the information validly and effectively, to reduce the number of animals used. Here, we used human corneal epithelial cells (hCECs) derived from donor cornea differentiated into three-dimensional (3D)-organotypic air-liquid interface (ALI), which resemble the features of the corneal epithelium. The 3D-organotypic ALI corneal epithelium was subjected to high-glucose conditions to generate a model of diabetic epitheliopathy. Our model showed well-established molecular and cellular characteristics of this pathology, such as epithelial defects and inflammation, with increased expression of IL-1β, TNF-α, p-NF-kB, COX-2, MMP-2 and MMP-9. The data provided highlight the utility of 3D-organotypic corneal epithelium in modeling diabetic epitheliopathy, offering new avenues in drug screening, as well as in precision and personalized medicine.

Optical coherence elastography (OCE) is a non-invasive imaging technique that measures the biomechanical properties of materials and tissues. This systematic review focuses on the applications of OCE in the anterior segment of the eye, including the cornea, iris, and crystalline lens, and its clinical relevance in diagnosing and managing ocular diseases. A systematic literature review was conducted using the PRISMA framework to identify studies published between 2014 and 2024. The review included studies that reported intrinsic biomechanical properties of anterior segment tissues measured using OCE. Databases searched included Scopus, Pub Med, and IEEE Xplore. Twenty-five studies met the inclusion criteria. The review found that OCE has been used to measure intrinsic biomechanical parameters such as Young's modulus and shear modulus in ocular tissues. OCE has been utilised to assess corneal stiffness in keratoconus, lens elasticity in presbyopia and cataract formation, and iris biomechanical changes under different lighting conditions. The studies demonstrated that OCE could detect subtle biomechanical changes associated with ocular diseases and measure treatment efficacy, such as collagen crosslinking for keratoconus management. The findings highlight the potential of OCE to enhance clinical diagnostics and patient care by providing detailed insights into the biomechanical properties of ocular tissues. However, variability in measurement techniques, the complexity of the method and reliance on animal models limit the current clinical translation of OCE. Standardised measurement protocols and further development andin vivovalidation are needed to overcome these barriers. OCE shows promise as a valuable non-invasive tool for high-resolution assessments of tissue biomechanics, which can subsequently support the diagnosis and management of ocular diseases. Future research should focus on standardising OCE methods and integrating them into clinical practice to fully realise their potential in improving patient outcomes.

The therapeutic potential of silk fibroin (SF) and hyaluronic acid (HA) composite hydrogels for corneal epithelial wound healing was assessed, focusing on the molecular weight of SF related to outcomes. Initially, SF of varying molecular weights was analyzed, and a medium molecular weight (M-SF; 10-72 kDa, average 40 kDa) was identified as most effective in promoting cell proliferation, attachment, and migration in various assays. A hydrogel formulation, H-SF/HA gel@M-SF, was then developed by incorporating M-SF (10-72 kDa, average 40 kDa) into a base hydrogel composed of high molecular weight SF (H-SF; 18-100 kDa, average 60 kDa) and HA. The physicochemical properties of the hydrogels, including pH balance, extensibility, and swelling rate, were characterized. The biological functions of the hydrogels were evaluated by using human corneal epithelial (HCE-T) cells and a mouse corneal injury model. H-SF/HA gel@M-SF exhibited supported enhanced expression of key genes associated with corneal repair, such as NOTCH I, GSK3β, ACTG, and VCL when compared with a serum-free medium. In vivo studies using mice demonstrated that H-SF/HA gel@M-SF achieved complete wound closure within 48 h, outperforming the H-SF/HA gel. These results underscore the significance of the SF molecular weight and concentration in hydrogel design and highlight the potential of H-SF/HA gel@M-SF for ophthalmic applications.

Glaucoma surgery impacts corneal graft survival differently by procedure type, with GDDs being most effective at reducing intraocular pressure. However, graft survival rates are comparable across trabeculectomy, CPC, and GDDs. Trabeculectomy improves visual acuity best but often requires additional interventions.

To investigate the impact of different glaucoma procedures on corneal graft survival and corneal endothelium health.

We searched PubMed, Cochrane Library, Scopus, and Web of Science, to identify eligible studies. Studies were included based on predetermined criteria. The primary outcome was corneal graft survival, and secondary outcomes included intraocular pressure (IOP) control, visual acuity, antiglaucoma medications, additional glaucoma surgery, and postoperative complications. Meta-analyses were conducted using random-effects models, and heterogeneity was assessed using the ( I2 ) test.

Our results included 27 studies involving 905 patients were analyzed. However, there were no randomized comparative studies. The overall proportion of corneal graft survival at the last follow-up was 66.4%, with the 3 subgroups of trabeculectomy, cyclophotocoagulation (CPC), and Glaucoma drainage devices (GDD) showing similar survival rates of 66.6%, 64.8%, and 65.6%, respectively. Short-term graft survival (6 mo) was similar across groups; however, 2-year survival favored trabeculectomy. GDDs were the most effective in reducing IOP with an average reduction of 21.4 mmHg compared with 18.9 mmHg for trabeculectomy and 14.8 mmHg for CPC. CPC yielded the best improvement in visual acuity reported as BCVA. GDD required the fewest postoperative antiglaucoma medications. Trabeculectomy had the highest proportion of patients needing additional surgery for glaucoma. The most common complications were hypotony, uveitis, and tube obstruction.

There were no significant differences in corneal graft survival rates among various glaucoma surgical techniques, but these findings must be interpreted with caution due to the limitations of primary research. GDDs effectively reduced IOP and minimized the need for antiglaucoma medications. Trabeculectomy may be associated with the greatest visual acuity improvement but may carry a higher likelihood of requiring further glaucoma surgery.

Herpes Keratitis (HK) is a debilitating infection of the cornea that remains the leading cause of infectious blindness in developed countries. Caused primarily by herpes simplex virus type 1 (HSV-1), it is associated with recurrent inflammation, leading to corneal scarring. This study investigated the initial events during acute HSV-1 infection in the cornea by adapting our human anogenital mucosal explant model to a HSV-1 infected porcine corneal explant model. We infected these corneas topically via high-density microarray patches (HD-MAPs) dipped in GFP-labelled HSV-1. Virus infection and spread was detected by both GFP protein and RNAscope, adapted for HSV-1 DNA. The punctures were consistent, usually in the epithelium but some extended into the underlying stroma. However, HSV-1 was restricted to the corneal epithelium, without spread through the anterior limiting membrane (ALM) or Bowman's layer into the stroma nor to the uppermost epithelial layer. This layer expressed SPRR1A similarly to the stratum granulosum of skin which is refractory to HSV-1 infection. In corneas where infected epithelial cells extended to the ALM, SPRR1A was also observed in this layer, suggesting it may contribute to its barrier function. Such studies of HSV-1 infection and spread will help improve therapy for HK and vaccine design to prevent it.

The cornea is the outermost transparent layer of the eye, and the continuous renewal of the corneal epithelium is important for its transparency. This process is primarily facilitated by corneal stem cells, most of which are found at the limbus. However, any deterioration or damage in this region leads to corneal conjunctivalization and consequent limbal stem cell deficiency (LSCD), which compromises corneal transparency. LSCD is an important condition, especially in the pediatric population, as it can lead to corneal vascularization, opacity and ultimately loss of vision and subsequent amblyopia, unlike adults. Although pediatric LSCD is often due to chemical injuries, as in adults, it is also caused by conditions such as congenital aniridia, Steven Johnson Syndrome and various other immunological disorders. Appropriate and timely treatment in pediatric LSCD is of particular importance in preventing progression to amblyopia, unlike adults. Accurate staging of the disease is essential for the necessary medical and surgical treatment decision. While medical approaches are at the forefront to eliminate the causative agent and improve the ocular surface in reversible cases, it is essential to replace the limbal stem cells lost in advanced disease. For these replacement procedures, it is noteworthy that there is a tendency for minimally invasive methods compared to adults to avoid possible complications due to long life expectancy in children. In conclusion, although there are various reviews on limbal stem cell deficiency (LSCD) in adults, we believe that this review for childhood LSCD will make an important contribution to the literature, since the relevant literature currently reported for the pediatric population is limited.

To define the normative data of corneal sensitivity in the pediatric age group, which currently lacks existing literature.

The study included 122 children aged 5 to 18 years who had applied for a routine ophthalmological examination at the Ege University Department of Ophthalmology. A total of 122 right eyes were included in the study. The study excluded children with any ocular pathologies, any previous ocular surgery, a history of contact lens use, and systemic diseases such as diabetes mellitus. Corneal sensitivity values were determined by means of a Cochet-Bonnet esthesiometer, applied to five distinct regions of the cornea (central, superior, inferior, nasal, and temporal).

The mean age was 11.29 ± 4.6 years (range: 2 to 18 years), and the female/male ratio was 63/59. The mean corneal sensitivity values of the central cornea and four corneal regions (superior, inferior, temporal, and nasal) were 5.16 ± 0.47, 5.16 ± 0.48, 5.19 ± 0.47, 5.18 ± 0.46, and 5.18 ± 0.45 cm, respectively. A negative correlation was identified between age and corneal sensitivity. No statistically significant difference was observed in corneal sensitivity when comparing quadrants or genders (P > .05).

Data delineating the typical values have been identified in adults and have been demonstrated to serve as a valuable diagnostic instrument, particularly in the context of neuropathy in diabetes. Nevertheless, to date, no normative data have been published for the pediatric age group. Therefore, this study makes a significant contribution to the field by pioneering the establishment of normative data for the pediatric age group regarding corneal sensitivity, as detected with the Cochet-Bonnet esthesiometer. [J Pediatr Ophthalmol Strabismus. 20XX;XX(X):XXX-XXX.].

Fungal keratitis has a poor prognosis given deep penetration into the corneal stroma. While Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) is a promising adjunct treatment for refractory cases, poor penetration limits its effectiveness. This study explores the penetration depth of alternative photosensitizers to address this issue.

Thirty-five human corneas were soaked for 30 minutes in 0.0075% solution of Rose Bengal disodium (n = 5), Rose Bengal lactone (n = 5), Erythrosin B disodium (n = 5), Erythrosin B lactone (n = 5), Eosin Y disodium (n = 5), Methylene blue (n = 5), or NaCl (control, n = 5). Confocal microscopy was used to assess penetration depth.

All photosensitizers penetrated greater into the cornea as compared to control. There was no significant difference in penetration between Rose Bengal lactone and Rose Bengal disodium (RB lactone: 106  ± 11 µm vs RB disodium: 99 ± 13 µm, p > 0.05). The penetration depths of the alternative photosensitizers was significantly greater than either Rose Bengal formulation (Erythrosin Blactone: 192 ± 31 µm, Erythrosin B disodium: 163 ± 13 µm, Eosin Y disodium: 249 ± 31 µm, Methylene Blue: 355 ± 151 µm).

Alternative photosensitizers exhibit superior penetration compared to Rose Bengal. However, antimicrobial efficacy and corneal safety require more robust evaluation before clinical use.

Keratoprosthesis is an alternative treatment for visual impairment caused by corneal diseases. However, due to the recognized postoperative complications in available Kpros, there is an exigency to explore potential alternative skirt materials for corneal implants. This study aims to investigate the suitability of poly(2-methoxyethyl methacrylate-co-2-hydroxyethyl methacrylate) (15% MEMA: 85% HEMA), and poly(2-phenoxyethyl methacrylate-co-2-hydroxyethyl methacrylate) (15% PhEMA: 85% HEMA) copolymers as a corneal implant material by evaluating their ability to adhere human keratocytes. The effect of chemical and mechanical properties of copolymers on the keratocyte cell adhesion was investigated. These copolymers are thermally stable with a glass transition temperature between 75 and 80 °C, and thermogravimetric analysis showed that the copolymers do not degrade until 190 °C. Sum frequency generation spectroscopy (SFG) and atomic force microscopy (AFM) were employed to evaluate the surface chemical and mechanical properties of the polymer thin films. SFG spectra showed the contributions of methylene (CH2) and α-methyl (α-CH3) functional groups at the air/polymer interface. Moreover, the signature vibrational modes of methoxy (-OCH3) and phenoxy (-OPh) groups were detected at the 15% MEMA: 85% HEMA and 15% PhEMA: 85% HEMA copolymer surfaces that contribute to chemical composition surface analysis. Meanwhile, the analysis of the AFM topographical images showed that the 15% MEMA: 85% HEMA copolymer is relatively rougher with a root-mean-square value of 56 nm but was found to be more elastic than the 15% PhEMA: 85% HEMA copolymer with a Young's modulus value of 0.39 GPa. Fluorescence microscopy images showed visible F-actin filaments on stiffer substrates, demonstrating the ability to regulate cell adhesion and migration behavior based on the nanomechanical characteristics of implants. The results show that substrate stiffness can regulate keratocyte cell adhesion as keratocytes preferred to adhere on a stiffer 15% PhEMA: 85% HEMA copolymer surface than the 15% MEMA: 85% HEMA copolymer surface.

Corneal endothelial cell dysfunction is a common cause of corneal decompensation in elderly. We describe a non-guttata corneal endothelial dystrophy with correlation of the clinical features to the histopathological and ultrastructural characteristics in a cohort of Saudi patients. A retrospective study of all consecutive cases of primary corneal decompensation in phakic eyes due to endothelial attenuation, in the absence of guttata is conducted. Patients were treated by either penetrating keratoplasty (PKP) or Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) as a primary procedure between 2002 and 2016. Clinical and demographic data were obtained through chart review and the histopathological data were collected by reviewing Descemet's membrane (DM) in the corneal tissue samples of the affected eyes. We included 17 eyes from 17 patients (10 females and 7 males), with a mean age of 67.17 ± 8.98 years. All patients were phakic, and decreased vision was the patients' main complaint at presentation. The pre-operative endothelial cell count was obtained in 3 eyes with a mean of 531.7 ± 309.5/mm2. Histopathology of the 17 corneal specimens showed thick multi-laminated DM and attenuated endothelium. The success rate of the primary procedure was 70%. The cornea of the other eye remained clear in 12/17 patients. This is a type of corneal endothelial cell dysfunction with a late onset of presentation, spontaneous corneal decompensation in phakic eyes or a rapid onset of decompensation following uncomplicated surgery. It seems to be asymmetrically bilateral among our Saudi patients. Fellow eyes are at the same risk of decompensation. DM lacks the presence of guttata clinically and histopathologically.

Diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy. Intravitreal anti-VEGF injections offer effective treatment, but they carry a risk of corneal epithelial detachment, particularly in patients who have recently undergone cataract surgery.

A 63-year-old male developed bilateral DME following cataract surgery with intraocular lens implantation. His best-corrected visual acuity (BCVA) was 0.15 in the right eye and 0.5 in the left eye. The patient underwent bilateral intravitreal injections of the anti-VEGF agent conbercept. During preparation for the injection in the left eye, corneal epithelial bleb formation was observed. The patient received corneal patching therapy, with complete epithelial healing observed by day 10 post-injection. This case underscores the need for vigilant corneal monitoring during and after intravitreal injections in diabetic patients with prior cataract surgery.

Close observation of corneal epithelial healing is crucial in diabetic patients receiving intravitreal injections, especially those with a recent history of cataract surgery. Careful pre-injection assessment and vigilant post-injection management are essential to mitigate this potential complication.

To ascertain the homing of monocytes and neutrophils in the epithelium versus stroma of HSV-1 infected corneas at different stages of infection and functional significance of their anatomical location in virus-infected corneas.

The corneas of C57BL/6J mice were infected with HSV-1 McKrae. Mice were euthanized on different days post-infection. The epithelium and stroma were separated from the infected corneas, and flow cytometry was performed to characterize the myeloid cell subsets in the epithelium versus the stromal layers of an infected cornea. MACS columns were used to purify neutrophils or deplete myeloid cells from infected corneas. Corneal epithelial scratch assay was performed to ascertain the impact of neutrophils on epithelium wound healing.

Our results showed a biphasic influx of monocytes in the epithelial but not the stromal layer of HSV-1-infected corneas. Furthermore, we noted the predominance of monocytes over neutrophils in the epithelium and the stromal layer of the cornea during the pre-clinical stage of corneal HSV-1 infection. However, neutrophils were the major myeloid cell subset in the epithelium and stroma during the clinical disease period of infection. Removal of monocytes from the infected epithelial layer during the pre-clinical stage promotes the dissemination of the virus. Interestingly, neutrophils localized in the corneal epithelium inhibit corneal epithelial wound healing.

Together, our data suggest that differential kinetics of monocytes and neutrophils homing in the epithelial layer regulate viral dissemination and epithelial wound healing in HSV-1-infected corneas.

The cornea, the transparent part of the anterior eye, is vital for light refraction and vision. This review examines the intricate chemical and biochemical interactions essential for maintaining corneal transparency and highlights significant advancements in corneal biology. The cornea comprises five layers: the epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium, each contributing uniquely to its structure and function. The epithelium, maintained by limbal stem cells, serves as a barrier and interacts with the tear film to maintain ocular surface health. The stroma, abundant in organized collagen fibrils and regulated by proteoglycans, is crucial for corneal clarity and biomechanical integrity, whereas the endothelium regulates corneal hydration and nutrition. Recent imaging advances have improved visualization of these molecular structures, enhancing our understanding of collagen organization and cross-linking. Proteoglycans such as decorin and lumican regulate collagen spacing and hydration, directly influencing corneal clarity. Biochemical processes within the cornea involve signaling molecules, growth factors, and cytokines, which are essential for wound healing, inflammation, and injury response. Despite progress, questions remain regarding corneal wound healing mechanisms, the impact of oxidative stress, and the roles of microRNAs. This review synthesizes recent discoveries to advance our understanding of corneal physiology and biochemical functions.

Topical ophthalmic drug delivery targeting the posterior segment of the eye has become a key area of interest due to its non-invasive nature, safety, ease of application, patient compliance, and cost-effectiveness. However, achievement of effective drug bioavailability in the posterior ocular segment is a significant challenge due to unique ocular barriers, including precorneal factors and anatomical barriers, like the cornea, the conjunctiva, and the sclera. Successful ocular drug delivery systems require increased precorneal residence time and improved corneal penetration to enhance intraocular bioavailability. A promising strategy to overcome these barriers is incorporating drug penetration enhancers (DPEs) into formulations. These compounds facilitate drug delivery by improving permeability across otherwise impermeable or poorly permeable membranes. At the ocular level, they act through three primary mechanisms: breaking tear film stability by interfering with the mucous layer; disrupting membrane components such as phospholipids and proteins; and loosening epithelial cellular junctions. DPEs offer significant potential to improve bioavailability and therapeutic outcomes, particularly for drugs targeting the posterior segment of the eye. This review is focused on analyzing the current literature regarding the use of penetration enhancers in topical ocular drug delivery, highlighting their mechanisms of action and potential to revolutionize ophthalmic treatments.

Fuchs Endothelial Corneal Dystrophy (FECD) is a corneal endothelial disease that causes microenvironment alterations and endothelial cell loss, which leads to vision impairment. It has a high global prevalence, especially in elderly populations. FECD is also one of the leading indications of corneal transplantation globally. Currently, there is no clearly defined canonical pathway for this disease, and it has been proposed that the combinatorial effects of genetic mutations and exogenous factors cause FECD. Clinical studies and observations have provided valuable knowledge and understanding of FECD, while preclinical studies are essential for gaining insights into disease progression and mechanisms for the development and testing of regenerative medicine therapies. In this review, we first introduce the proposed genetic and molecular pathologies of FECD. Notably, we discuss the impact of abnormal extracellular matrix deposition (guttata), endothelial-to-mesenchymal transition, cell senescence, and oxidative stress on the pathology and etiology of FECD. We review and summarize the in vitro cell models, ex vivo tissues, and in vivo animal models used to study FECD. The benefits and challenges of each model are also discussed.

Corneal transplantation remains a critical treatment option for individuals with corneal disorders, but it faces challenges such as rejection, high associated medical costs, and donor scarcity. A promising alternative for corneal replacement involves fabricating artificial cornea from a patient's own cells. Our study aimed to leverage bioprinting to develop a corneal model using human corneal stromal cells embedded in a collagen-based bioink. We generated both cellular and acellular collagen I (COL I) constructs. Cellular constructs were cultured for up to 4 weeks, and gene expression analysis was performed to assess extracellular matrix (ECM) remodeling and fibrotic markers. Our results demonstrated a significant decrease in the expression of COL I, collagen III (COL III), vimentin (VIM), and vinculin (VCL), indicating a dynamic remodeling process towards a more physiologically relevant corneal ECM. Overall, our study provides a foundational framework for developing customizable, corneal replacements using bioprinting technology. Further research is necessary to optimize the bioink composition and evaluate the functional and biomechanical properties of these bioengineered corneas.

The distinctive benefits and drawbacks of various drug delivery strategies to supply corneal tissue improvement for sense organs have been the attention of studies worldwide in recent decades. Static and dynamic barriers of ocular tissue prevent foreign chemicals from entering and inhibit the active absorption of therapeutic medicines. The distribution of different medications to ocular tissue is one of the most appealing and demanding tasks for investigators in pharmacology, biomaterials, and ophthalmology, and it is critical for cornea wound healing due to the controlled release rate and increased drug bioavailability. It should be mentioned that the transport of various types of medications into the different sections of the eye, particularly the cornea, is exceedingly challenging because of its distinctive structure and various barriers throughout the eye. Nanoparticles are being studied to improve medicine delivery strategies for ocular disease. Repetitive corneal drug delivery using biodegradable nanocarriers allows a medicine to remain in different parts of the cornea for extended periods of time and thus improve administration route effectiveness. In this review, we discussed eye anatomy, ocular delivery barriers, as well as the emphasis on the biodegradable nanomaterials ranging from organic nanostructures, such as nanomicelles, polymers, liposomes, niosomes, nanowafers, nanoemulsions, nanosuspensions, nanocrystals, cubosomes, olaminosomes, hybridized NPs, dendrimers, bilosomes, solid lipid NPs, nanostructured lipid carriers, and nanofiber to organic nanomaterials like silver, gold, and mesoporous silica nanoparticles. In addition, we describe the nanotechnology-based ophthalmic medications that are presently on the market or in clinical studies. Finally, drawing on current trends and therapeutic approaches, we discuss the challenges that innovative optical drug delivery systems confront and propose future research routes. We hope that this review will serve as a source of motivation and inspiration for developing innovative ophthalmic formulations.

This study presents a numerical model investigating the thermal effects of laser exposure on the cornea and retina of the human eye, with a focus on the role of blood flow in thermoregulation. Both the anterior and posterior segments of the eye are analysed to provide guidance on whether to account for blood flow in simulations of laser-based eye surgeries. Argon Fluoride (ArF), Holmium:Yttrium-Aluminum-Garnet (Ho:YAG), Neodymium-Doped:Yttrium-Aluminum-Garnet (Nd:YAG), and Ruby lasers are applied to a three-dimensional eye model. The Pennes' bio-heat transfer equation is solved using the Finite Element Method (FEM) to assess temperature distributions and penetration depths, ensuring that target tissues remain within safe temperature limits. The simulation results show maximum temperatures of 259°C, 89.2°C, 136°C, and 67.4°C for ArF, Ho:YAG, Nd:YAG, and Ruby lasers, respectively. Additionally, the explicit method is employed to model the pupil axis and further investigate blood flow's impact on thermoregulation. The inclusion of blood flow results in lower temperatures across all laser conditions, demonstrating its crucial role in regulating excess heat, particularly in the retina, which has a denser blood vessel network compared to the avascular cornea. These findings emphasise the importance of incorporating blood flow in thermal simulations to improve the accuracy of predictions and ensure safer outcomes in laser-based eye surgeries. This study employs a comprehensive approach combining precise modelling, simulations, and numerical analysis to investigate the effects of lasers on both the cornea and retina. This offers a wide understanding of laser-tissue interactions and helps in optimizing treatment parameters for both types of ocular tissues. Finally, a comparison table is presented alongside existing studies to highlight the achieved temperatures and penetration depths in laser-tissue interactions.

To evaluate the effects of smoking on ocular surface through comprehensive analysis of corneal nerves, corneal epithelium, dendritic cells (DCs), and clinical assessments.

This cross-sectional study included 250 healthy smokers and 272 healthy non-smokers. Patients' smoking status and duration were recorded. In vivo confocal microscopy was performed to assess 7 quantitative corneal nerves parameters, 3 corneal neuroma parameters, 3 DCs parameters, and 3 epithelial parameters. Ocular surface evaluations included tear break-up time (TBUT), ocular surface and corneal staining, corneal sensitivity, and Schirmer test. Ocular Surface Disease Index questionnaire was used for symptom assessment.

Compared to non-smokers, smokers exhibited significantly lower corneal nerve fiber density (CNFD), nerve branch density, nerve fiber length, nerve total branch density, corneal nerve fiber area (CNFA), and corneal nerve fractal dimension (CFracDim; all p < 0.001). Smokers also presented with a significantly swollen corneal nerve fiber (p < 0.001). Longer smoking duration was significantly associated with lower CNFD (β = -0.04, P = 0.010), lower CNFA (β = -0.00002, P = 0.033), and lower CFracDim (β = -0.0008, P = 0.016). Additionally, a significantly larger neuroma total area (p = 0.040), size (p < 0.001) and perimeter (p < 0.001), as well as a significantly higher DCs density (p < 0.001), DCs count (p = 0.003), and lower DCs elongation which suggested higher DCs maturity (p < 0.001), were observed in the smoking group. Smokers demonstrated significantly higher ocular surface staining scores (p < 0.001) and reduced TBUT (p = 0.001). Corneal epithelial circularity was borderline higher in the smoking subjects (p = 0.059).

Smoking is associated with significant alterations in corneal nerve morphology and quantity, increased immunological cells, and compromised ocular surface integrity.

Affecting a large proportion of the population worldwide, corneal disorders constitute a concerning health hazard associated to compromised eyesight or blindness for most severe cases. In the last decades, mesenchymal stem/stromal cells (MSCs) demonstrated promising abilities in improving symptoms associated to corneal diseases or alleviating these affections, especially through their anti-inflammatory, immunomodulatory and pro-regenerative properties. More recently, MSC therapeutic potential was shown to be mediated by the molecules they release, and particularly by their extracellular vesicles (EVs; MSC-EVs). Consequently, using MSC-EVs emerged as a pioneering strategy to mitigate the risks related to cell therapy while providing MSC therapeutic benefits. Despite the promises given by MSC- and MSC-EV-based approaches, many improvements are considered to optimize the therapeutic significance of these therapies. This review aspires to provide a comprehensive and detailed overview of current knowledge on corneal therapies involving MSCs and MSC-EVs, the strategies currently under evaluation, and the gaps remaining to be addressed for clinical implementation. From encapsulating MSCs or their EVs into biomaterials to enhance the ocular retention time to loading MSC-EVs with therapeutic drugs, a wide range of ground-breaking strategies are currently contemplated to lead to the safest and most effective treatments. Promising research initiatives also include diverse gene therapies and the targeting of specific cell types through the modification of the EV surface, paving the way for future therapeutic innovations. As one of the most important challenges, MSC-EV large-scale production strategies are extensively investigated and offer a wide array of possibilities to meet the needs of clinical applications.

The cornea needs to be transparent to visible light and precisely curved to provide the correct refractive power. Both properties are governed by its structure. Corneal transparency arises from constructive interference of visible light due to the relatively ordered arrangement of collagen fibrils in the corneal stroma. The arrangement is controlled by the negatively charged proteoglycans surrounding the fibrils. Small changes in fibril organisation can be tolerated but larger changes cause light scattering. Corneal keratocytes do not scatter light because their refractive index matches that of the surrounding matrix. When activated, however, they become fibroblasts that have a lower refractive index. Modelling shows that this change in refractive index significantly increases light scatter. At the microscopic level, the corneal stroma has a lamellar structure, the parallel collagen fibrils within each lamella making a large angle with those of adjacent lamellae. X-ray scattering has shown that the lamellae have preferred orientations in the human cornea: inferior-superior and nasal-temporal in the central cornea and circumferential at the limbus. The directions at the centre of the cornea may help withstand the pull of the extraocular muscles whereas the pseudo-circular arrangement at the limbus supports the change in curvature between the cornea and sclera. Elastic fibres are also present; in the limbus they contain fibrillin microfibrils surrounding an elastin core, whereas at the centre of the cornea, they exist as thin bundles of fibrillin-rich microfibrils. We present a model based on the structure described above that may explain how the cornea withstands repeated pressure changes due to the ocular pulse.

Recent advancements in biomaterials have significantly impacted wearable health monitoring, creating opportunities for personalized and non-invasive health assessments. These developments address the growing demand for customized healthcare solutions. Durability is a critical factor for biomaterials in wearable applications, as they must withstand diverse wearing conditions effectively. Therefore, there is a heightened focus on developing biomaterials that maintain robust and stable functionalities, essential for advancing wearable sensing technologies. This review examines the biomaterials used in wearable sensors, specifically those interfaced with human skin and eyes, highlighting essential strategies for achieving long-lasting and stable performance. We specifically discuss three main categories of biomaterials-hydrogels, fibers, and hybrid materials-each offering distinct properties ideal for use in durable wearable health monitoring systems. Moreover, we delve into the latest advancements in biomaterial-based sensors, which hold the potential to facilitate early disease detection, preventative interventions, and tailored healthcare approaches. We also address ongoing challenges and suggest future directions for research on material-based wearable sensors to encourage continuous innovation in this dynamic field.

Background and Objectives: The cornea protects the eye from external influences and contributes to its refractive power. Corneas belong to the most frequently transplanted tissues, providing a last resort for preserving the patient's vision. There is a high demand for donor corneas worldwide, but almost 4% of these transplants are not eligible due to microbial contamination. The objective of this study is to ascertain the suitability of 222 nm Far-UVC irradiation for the decontamination of corneas without damaging corneal endothelial cells. Materials and Methods: To assess the destructive effect of irradiation and, thus, identify the applicable dose needed to decontaminate the cornea without interfering with its integrity, 141 porcine corneas were irradiated with 0, 60 or 150 mJ/cm2 at 222 nm. In the second step, a series of 13 human corneas were subjected to half-sided irradiation using 15 or 60 mJ/cm2 at 222 nm. After five days of in vitro culturing, the endothelial cell density of the non-irradiated area of each human cornea was compared to the irradiated area. Results: Irradiation with up to 60 mJ/cm2 had no detectably significant effect on the cell integrity of human corneas (p = 0.764), with only a minimal reduction in cell density of 3.7% observed. These findings were partially corroborated by tests on porcine corneas, wherein the variability between test groups was consistent, even at increased irradiation doses of up to 150 mJ/cm2, and no notable effects on the irradiated porcine endothelium were monitored. The efficacy of the antimicrobial treatment was evident in the disinfection tests conducted on corneas. Conclusions: These initial irradiation experiments demonstrated that 222 nm Far-UVC radiation has the potential to decontaminate the cornea without compromising sensitive endothelial cell viability.

Laser refractive surgeries are a safe option for low-to-moderate refractive corrections, providing excellent visual outcomes. Over the years, various procedures have been introduced into clinical practice, but the most performed today remain Photorefractive Keratectomy (PRK), Laser In-Situ Keratomileusis (LASIK), and Small Incision Lenticule Extraction (SMILE). Although laser refractive treatments are considered safe, clinicians have focused on the risk of post-surgical ectasia, a rare but serious complication. Ectasia is characterized by progressive corneal thinning and steepening, leading to vision distortion, irregular astigmatism, and in some cases, a reduction of visual acuity. It is still debated whether laser refractive surgeries can cause ectasia as an iatrogenic condition or merely accelerate the progression of an underlying corneal pathology, not detected during pre-surgical screening. The proposed work investigates the relationship among three laser refractive surgeries (PRK, LASIK and SMILE), currently performed in clinical practice, and ectasia onset and progression by means of an in silico analysis.

An average 3D finite-element corneal model is developed and a pathological area, characterized by reduced stiffness of varying severity grades, is defined to analyze its influence on ectasia development and progression in the pre-surgical state. Three laser treatments (PRK, LASIK and SMILE) are simulated on healthy and pathological models. Pre- and post-surgical conditions are compared to check whether any procedure worsens the pre-surgical pathological state. The optomechanical effect of each procedure on the cornea is analyzed at both healthy and pathological conditions and compared to establish which refractive procedure mostly affects corneal structure.

While the three refractive procedures showed different behaviors in terms of mechanical changes affecting the cornea, from an optical perspective, as the pathology severity worsened, none of the surgeries caused a worsening in the cone's severity with respect to pre-surgical pathological conditions. This result suggests that surgeries may have a limited role in causing post-surgical ectasia, as it seems more plausible that they accelerate the progression of an underlying pathological condition. Among the three procedures, PRK was found to be the least invasive treatment from a mechanical perspective, while SMILE showed the greatest impact on the posterior surface, suggesting a potential long-term risk for ectasia progression.

This review seeks to evaluate anterior segment optical coherence tomography (AS-OCT) in the diagnostic procedure and management of Descemet's membrane detachment (DMD) in cataract surgery. DMD may present diagnostic challenges, particularly in pronounced corneal edema where traditional methods such as slit lamp biomicroscopy may be inadequate in evaluating the corneal layers. The role of AS-OCT in providing high-resolution images in the preoperative, intraoperative, and postoperative phases of cataract surgery is analyzed with a focus on its role in the early diagnosis of DMD and in evaluating the extent, morphology, and topographic localization of DMD allowing for immediate intervention during surgery and precise pneumodescemetopexy procedures where conservative treatment has failed. This review explores the integration of AS-OCT into the standard perioperative diagnostic workflow, highlighting its potential role in the prevention, accurate diagnosis, and prompt management of DMD, a complication of cataract surgery that, while low in incidence, can be highly disruptive when it occurs. The emerging role of artificial intelligence (AI) in AS-OCT analysis of anterior segment conditions and surgical procedures is discussed, though refinement of AI algorithms is warranted.

The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases. DNA methylation can regulate gene expression, thereby affecting cell function and signal transduction. Ophthalmic diseases are a kind of complex diseases, and their pathogenesis involves many factors such as genetic, environmental and individual differences. In addition, inflammation, oxidative stress and lipid metabolism, which abnormal DNA methylation is closely related to, are also considered to be major factors in eye diseases. The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive. In addition to the simple suppression of gene expression by hypermethylation, factors such as hypomethylation or demethylation, DNA methylation in non-promoter regions, interactions with other epigenetic modifications, and dynamic changes in DNA methylation must also be considered. Interestingly, although some genes are at abnormal methylation levels, their expression is not significantly changed, which indirectly reflects the complexity of gene regulation. This review aims to summarize and compare some relevant studies, and provide with new ideas and methods for the prevention and treatment of different eye diseases, such as glaucoma, retinoblastoma, and diabetic retinopathy.

Background/Objectives: The evaluation of the differences in corneal epithelial thickness profiles in healthy eyes and eyes with mild and moderate stages of keratoconus, using optical coherence tomography (OCT). Methods: Fifty-two healthy eyes (group 0), forty-one eyes with mild keratoconus (group I), and thirty eyes with moderate keratoconus (group II) were included in this study. Only one of the patient's eyes was enrolled, and they were divided into groups using the Amsler-Krumeich (A-K) classification-stage I and II. All patients underwent a visual acuity assessment, slit-lamp examination, corneal tomography, and automatic mapping of corneal thickness and epithelial thickness on a diameter of 9 mm. Corneal tomography with a Placido/Scheimpflug instrument (Sirius, CSO, Florence, Italy) and OCT with a corneal adaptor module (Avanti RTVue XR, Optovue, Lombard, IL, USA) were used. Results: Minimum corneal epithelium thickness was 49.5, 43, and 40 µm in groups 0, I, and II, respectively (Kruskal-Wallis test, p < 0.001). A moderate correlation was found between minimum epithelial thickness and the apex curvature (Pearsons's coefficient r = -0.62, p < 0.001) and posterior radius of central corneal curvature (Pearsons's coefficient r = 0.62, p < 0.001). The difference between minimum and maximum epithelial thickness showed a high correlation (r = -0.770, p < 0.001). In groups I and II, on corneal epithelial thickness maps the thinnest sector, located inferiorly and temporally to the center, was surrounded by sectors with increased thickness. Conclusions: At the apex of the cone, the corneal epithelium becomes thinner, and a thicker ring forms around the cone. Although there is a moderate-to-strong correlation to parameters linked with the severity of keratoconus, and minimum epithelial thickness as well as the minimum-maximum difference, it is not possible to establish cut-off values for stages I and II in the Amsler-Krumeich (A-K) classification.

Transmucosal drug products, such as aerosols, films, semisolids, suppositories, and tablets, have been developed for the treatment of various human diseases and conditions. Transmucosal drug absorption is highly influenced by the biological structures of the mucosa and the physiological environment specific to the administration route (e.g., nasal, rectal, and vaginal). Over the last few decades, in vitro permeation testing (IVPT) using animal tissues or in vitro cell cultures have been utilized as a cost-effective and efficient tool for evaluating drug release and permeation behavior, assisting in formulation development and quality control of transmucosal drug delivery systems. This review summarizes the key mucosal permeation barriers associated with representative transmucosal administration routes, as well as considerations for IVPT method development. It highlights various IVPT methods, including vertical diffusion cell, flow-through diffusion cell, Ussing chamber, and transwell systems. Additionally, future perspectives are discussed, such as the use of optical methods to study in vitro drug permeation and the development of in vitro-in vivo correlation (IVIVC) for transmucosal drug development. The potential of IVPT as part of in vitro bioequivalence assessment strategies for locally acting transmucosal drug products is also highlighted.

The cornea is a transparent avascular tissue that serves as the first line of defense against opportunistic pathogens and provides a smooth refractive surface for vision. Due to its external location, the cornea is vulnerable to stress from the outer environment. This can lead to corneal epithelial breakdown and subsequent corneal disease. Extracellular vesicles (EVs) are nano-sized vesicles enclosed within a lipid bilayer that are secreted by all cells in the body and play a key role in cell-to-cell communication. Within the cornea field, EVs and exosomes, the latter of which represents a subpopulation of small EVs, have emerged as potential therapies for treating corneal diseases and have increased our understanding of the mechanisms by which EVs, and more specifically, exosomes released by stressed or unhealthy cells, leads to corneal dysfunction and disease.

We conducted a literature search using PubMed and Google Scholar using keywords relevant to exosomes, extracellular vesicles, and cornea. We reviewed the literature focusing on EV studies on corneal wound healing and therapy.

This review provides a comprehensive overview of the current state of exosome biology as it relates to corneal disease and wound healing. Studies to date provide compelling data indicating that EVs and exosomes may play an integral role in the maintenance of corneal homeostasis. EVs and exosomes also have exciting potential as therapeutics in corneal wound healing and disease; and their presence in tear fluid may serve as potential diagnostic biomarkers for ocular and systemic diseases.

While corneal exosome biology is still in its infancy state, continued progress in this area will improve our understanding of the functional capacity of these small vesicles in the human cornea and may lead to the development of novel regenerative therapies.

For all vertebrates, the anterior eye structures work together to protect and nourish the eye while ensuring that light entering the eye is correctly focused on the retina. However, the anterior eye structure can vary significantly among different vertebrates, reflecting how the structures of the anterior eye have evolved to meet the specific visual needs of different vertebrate species. Although conserved pathways regulate fundamental aspects of anterior eye development in vertebrates, there may also be species-specific differences underlying structural variation. Our knowledge of the cellular and molecular mechanisms underlying the development of structures of the anterior eye comes mainly from work in mammals, chicks, some amphibians, and small teleosts such as zebrafish. Our understanding of anterior eye development would benefit from comparative molecular studies in diverse vertebrates. A promising lizard model is the brown anole, Anolis sagrei, which is easily raised in the laboratory and for which genome editing techniques exist. Here, we provide a detailed histological analysis of the development of the anterior structures of the eye in A. sagrei, which include the cornea, iris, ciliary body, lens, trabecular meshwork, and scleral ossicles. The development of the anterior segment in anoles follows a pattern similar to other vertebrates. The lens forms first, followed by the cornea, iris, ciliary body, and tissues involved in the outflow of the aqueous humor. The development of the iris and ciliary body begins temporally and then proceeds nasally. Scleral ossicle development is generally comparable to that reported for chicks and turtles. Anoles have a remarkably thin cornea and a flat ciliary body compared to the eyes of mammals and birds. This study highlights several features in anoles and represents a deeper understanding of reptile eye development.

The cornea is the primary refracting surface of the eye, requiring precise curvature to ensure optimal vision. Any distortion in its shape may result in significant visual impairment. Corneal ectasias, such as keratoconus (KC), is characterized by gradual thinning and protrusion of the thinned area, due to biomechanical weakening of the tissue, leading to astigmatism and vision loss. KC affects approximately 1 in 2000 individuals globally. While corneal transplantation is the main treatment, limited donor availability and potential immunogenic reactions have spurred the search for alternatives. Stromal lenticule implantation using decellularized porcine corneas offers a promising solution, with reduced immunogenicity and risk of rejection. Additionally, combining this approach with riboflavin and UV radiation treatment post-surgery enhances collagen fibril cross-linking, promoting tissue integration and organization. This study evaluated the efficacy of heterologous transplantation of decellularized porcine lenticules into the corneal stroma of rabbits, followed by riboflavin application and UV radiation. Results demonstrated increased stromal thickness and no signs of tissue rejection, indicating minimal immunogenicity of the lenticules. The cross-linking technique successfully improved tissue organization, suggesting that xenographic lenticule implantation, combined with riboflavin and UV light, is a promising alternative for treating corneal ectasias like KC. Further research is necessary to confirm the long-term efficacy and safety of this method in human subjects.

The ability to "switch on" adhesion between a thin hydrogel and a biological tissue can be useful in biomedical applications such as surgery. One way to accomplish this is with an electric field, a phenomenon termed electroadhesion (EA). Here, it is shown that cationic gels can be adhered by EA to tissues across all of biology. This includes tissues from animals, including humans and other mammals; birds; fish; reptiles (e.g., lizards); amphibians (e.g., frogs), and invertebrates (e.g., shrimp, worms). Gels can also be adhered to soft tissues from plants, including fruit (e.g., plums) and vegetables (e.g; carrot). In all cases, EA is induced by a low electric field (DC, 10 V) applied for a short time (20 s). After the field is removed, the adhesion persists. The adhesion can also be reversed by applying the field with opposite polarity. In mammals, EA is strong for many tissues (e.g., arteries, muscles, and cornea), but not others (e.g., adipose, brain). Tissues with anisotropic structure show anisotropic adhesion strength by EA. The higher the concentration of anionic polymers in a tissue, the stronger its adhesion to cationic gels. This underscores that EA is mediated by the electrophoresis of chain segments across the gel-tissue interface.

Anterior eye disorders including dry eye syndrome, keratitis, chemical burns, and trauma have varying prevalence rates in the world. Classical dosage forms based-topical ophthalmic drugs are popular treatments for managing corneal diseases. However, current dosage forms of ocular drugs can be associated with major challenges such as the short retention time in the presence of ocular barriers. Developing alternative therapeutic methods is required to overcome drug bioavailability from ocular barriers. Nanocarriers are major platforms and promising candidates for the administration of ophthalmic drugs in an adjustable manner. This paper briefly introduces the advantages, disadvantages, and characteristics of delivery systems for the treatment of corneal diseases. Additionally, advanced technologies such as 3D printing are being considered to fabricate ocular drug carriers and determine drug dosages for personalized treatment. This comprehensive review is gathered through multiple databases such as Google Scholar, PubMed, and Web of Science. It explores information around "ocular drug delivery systems'', "nano-based drug delivery systems'', "engineered nanocarriers'', and "advanced technologies to fabricate personalized drug delivery systems''.

3D printing, also known as additive manufacturing, continues to reshape manufacturing paradigms in healthcare by providing customized on-demand object fabrication. However, stereolithography-based 3D printers encounter a conflict between optimizing printing parameters, requiring more time, and print efficiency, requiring less time. Moreover, commonly used metrics to assess shape fidelity of 3D printed hydrogel materials like 'circularity' and 'printability' are limited by the soft nature of hydrogels, that can cause irregularities in their boundary. To unlock the full potential of 3D printing of biomaterials, it is also necessary to understand correlation between printing parameters and ink properties. In this work, a method based on curing depth, overcuring (cumulative cure), and print thickness was developed, which enables a time-efficient and reliable determination of printing conditions for complex geometries using gelatin methacrylate hydrogel biomaterial ink. We also examined the impact of printing direction on the print quality in terms of object/print thickness and aspect ratio. Moreover, the effects of dye concentration, exposure time, and layer thickness on print quality were evaluated, with discussions focused on the correlation between print dimension to layer thickness. Further evaluation was achieved by successfully printing bioinspired corneal stroma-like scaffold and delicate structures like a contact lens and a model eyeball, substantially expanding the scope of this method in producing high-quality prints with intricate details. We also demonstrate the effectiveness of 'Feret ratio,' another measure of object shape, in assessing the shape fidelity of different prints. Overall, the results highlight the practical potential of this method in enhancing the speed and reliability of the 3D printing processes involving complex geometries using a low-cost 3D printers.

The challenge of treating corneal scarring through keratoplasties lies in the limited availability of donor tissue. Various studies have shown the therapeutic use of cultivated corneal stromal stem cells (CSSCs) to mitigate tissue inflammation and suppress fibrosis and scar tissue formation in preclinical corneal wound models. To develop CSSC therapy for clinical trials on patients with corneal scarring, it is necessary to generate clinical-grade CSSCs in compliant to Good Manufacturing Practice (GMP) regulations. This chapter elucidates human CSSC isolation, culture, and cryopreservation under GMP-compliant conditions. It underscores quality assessment encompassing morphological traits, expression of stemness markers, anti-inflammatory activity, and keratocyte differentiation potency.

The present avian anatomists have shown a renewed interest in looking at whether the structure of the avian eyelid is accommodated by the kinetic achievement for each eyelid. The current work utilised both histological and anatomical methods to explore the eyelid's structural association with their kinetic, utilising the hoopoe and cattle egret as natural models. The third lid moved only without implicating other lids. Wrinkles on the edge of the hoopoe's eyelid became less pronounced during the opening phase, in contrast to, the edge of the egret's eyelid. The elevator muscle was visible only in the hoopoe, while both birds possessed the retractor anguli oculi muscles. The two later muscles collaborate with the depressor muscle during the closure phase. Two types of collagen I and III were detected within the stroma of the eyelids of both bird species; the elastic fibres was observed; few were in the hoopoe's eyelids. The eyelid edge of the hoopoe has more of the elastic fibres than those in its eyelid skin. The hoopoe's eyelid's epithelial layers contained more cytokeratin (AE1/AE3) than the egret. In conclusion, the anatomical traits of the hoopoe eyelids contribute to its greater motion compared to the egret eyelids.

Background/Objectives: Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS) are neurodevelopmental disorders (NDDs) with overlapping symptoms, suggesting a partially shared genetic origin. This study investigates the prevalence of connective tissue-related conditions in individuals with ASD, ADHD, or TS. Methods: A questionnaire was administered to families of 120 individuals with ASD, ADHD, or TS, collecting sociodemographic data and examining 10 types of disorders affecting various organs and systems. Statistical analyses were performed using STATA 16.0, with the significance level set at 5%. Results: Among the 120 patients, 48 had ASD, 36 had ADHD, and 36 had TS. Flat feet were significantly more common in individuals with ASD (52.1%; OR 7.20; p < 0.001), ADHD (52.8%; OR 6.73; p = 0.001), and TS (38.9%; OR 3.70; p = 0.034) compared to controls (13.6%). Hypersensitivity was more frequent in individuals with ASD (56.3%; OR 5.90; p = 0.001), ADHD (50.0%; OR 4.11; p = 0.011), and TS (58.3%; OR 5.35; p = 0.003) compared to controls (18.2%). Myopia and ptosis were more common in ADHD (30.6%). There was a possible trend towards orthodontic device use in TS (OR 3.20; p = 0.076). Flat feet and hypersensitivity were also common in fathers (31.0% and 36.4%, respectively), mothers (31.0% and 15.2%), and patients (43.8% and 55%). Conclusions: The findings of this study highlight the significant associations between ASD, ADHD, and TS and specific physical symptoms, such as flat feet, sensory hypersensitivity, and other connective tissue-related manifestations. The familial prevalence of these symptoms suggests a potential genetic underpinning, further supporting the hypothesis of shared aetiological pathways. These insights underscore the need for interdisciplinary research to explore the mechanisms linking neurodevelopmental and connective tissue disorders, aiming to improve diagnosis and management strategies.

Human eyes have the most complex and advanced physiological defense barriers. Due to these barriers, efficient delivery of ocular drugs is a major challenge in the treatment of eye diseases and disorders. Posterior eye diseases such as retinopathy are the leading causes of impaired vision and blindness globally. The topical and systemic administration of drugs such as eye drops, ointments, intravitreal injections, intraocular implants, contact lenses, and emulsions are the perennial approaches employed to treat ocular diseases. However, these modalities are inefficient due to the low bioavailability of the active drug and the potential for drug-related cytotoxicity to the ocular tissue. In this review, the conventional approaches in ocular drug delivery systems (DDSs) are explored and the limitations associated with each technique are elucidated. A comparison between the different DDSs is presented, showing the most effective treatment techniques available to date. In addition, this review presents recent advances in the field of nanocarriers and microcarriers used in ocular drug delivery systems such as nanoparticles, nano-suspensions, nanofibers, nanogels, nano-liposomes, nano micelles, dendrimers, contact lens, microneedle, and implants. Further, this review identifies the utility of nano-carriers in enabling the development of new-generation ocular DDSs with low toxicity, high efficiency, and high stability of targeted drug delivery systems to overcome the limitations observed with conventional ocular DDSs. In addition, this manuscript sheds light on the incidence and unique landscape of ocular diseases in the United Arab Emirates (UAE), and the potential for employing novel ocular DDSs for targeted treatment of conditions such as diabetic retinopathy in the UAE. It also discusses the putative role genetic variants of the VEGF gene may play in predisposing the local population in the UAE to developing posterior eye segment diseases such as retinopathy.

After reporting the first known clinical case associating compound heterozygous single-nucleotide variants in Exon 2 of ZNF469 to aortic aneurysmal and iliac dissection, we began prospective surveillance in our vascular genetic practice for similar cases. Herein, we present nine (9) subjects from a total cohort of 135 with arterial aneurysms or dissections who revealed single-nucleotide variants in ZNF469 with no other alterations in a panel of 35 genes associated with aneurysmal and dissection disorders. Five out of nine (5/9) single-nucleotide variants were in Exon 1, and four out of nine (4/9) mutations were in Exon 2, both of which are principal coding exons for this gene. Eight out of nine (8/9) were ACMG variants of unknown significance (VUSs), and one out of nine (1/9) was an ACMG pathogenic mutation previously associated to brittle cornea syndrome (BCS). Of our nine subjects, four (44.4%) experienced clinically significant vascular dissection, and four (44.4%) had a family history of one or more first-degree relatives with aneurysmal or dissection diseases. This novel genetic case series significantly strengthens our initial discovery of ZNF469's potential association with arterial aneurysmal/dissection diseases through the study of this cohort of unrelated patients.

Annotation with widely used, well-structured ontologies, combined with the use of ontology-aware software tools, ensures data and analyses are Findable, Accessible, Interoperable and Reusable (FAIR). Standardized terms with synonyms support lexical search. Ontology structure supports biologically meaningful grouping of annotations (typically by location and type). However, there are significant barriers to the adoption and use of ontologies by researchers and resource developers. One barrier is complexity. Ontologies serving diverse communities are often more complex than needed for individual applications. It is common for atlases to attempt their own simplifications by manually constructing hierarchies of terms linked to ontologies, but these typically include relationship types that are not suitable for grouping annotations. Here, we present a suite of tools for validating user hierarchies against ontology structure, using them to generate graphical reports for discussion and ontology views tailored to the needs of the HuBMAP Human Reference Atlas, and the Human Developmental Cell Atlas. In both cases, validation is a source of corrections and content for both ontologies and user hierarchies.