Search Results (67)

Corneal sensitivity is an important indicator of corneal health and innervation. Corneal hypoesthesia may be an early indicator of corneal diseases such as neurotrophic keratopathy. Various instruments have been used to measure corneal sensitivity, the first being the Cochet–Bonnet aesthesiometer. Over the years, new devices employing different stimuli have been developed, such as the gas-based Belmonte aesthesiometer, the Swiss liquid-jet aesthesiometer, and the most recently released corneal Brill aesthesiometer. In this review, the progress and advancement of aesthesiometers since their introduction is described. The mechanism, advantages, and disadvantages of these aesthesiometers are discussed and compared. We also report the relationship between corneal sensitivity and corneal innervation in various conditions, including diabetes mellitus, Fuchs’ endothelial dystrophy, dry eye disease, glaucoma, keratoconus, herpes simplex keratitis, post-refractive surgery, and ocular graft-versus-host disease. Through this review, we aim to highlight the importance of the assessment of corneal sensitivity and innervation in the diagnosis, treatment, and monitoring of anterior and posterior segment ocular disorders. Full article

Oculomics is an emerging field that leverages ophthalmic imaging data to identify biomarkers of systemic disease, facilitating early diagnosis and risk stratification. Despite its growing recognition, gaps remain in the literature regarding the clinical applications of oculomics. Various systemic diseases—including metabolic disorders (e.g., diabetes mellitus), infectious diseases (e.g., COVID-19), neurodegenerative diseases (e.g., dementia), hematologic disorders (e.g., thalassemia), autoimmune conditions (e.g., rheumatoid arthritis), and genetic syndromes (e.g., Fabry disease)—exhibit ocular manifestations detectable through in vivo confocal microscopy and anterior segment optical coherence tomography, among other imaging modalities. Increasing evidence supports the role of corneal imaging in identifying systemic disease biomarkers, a process further enhanced by artificial intelligence-driven analyses. This review synthesizes the current findings on corneal biomarkers of systemic disease, their ophthalmic imaging correlates, and the expanding role of corneal oculomics in translational medicine. Additionally, we explore future directions for integrating oculomics into clinical practice and biomedical research. Full article

Background: Sirtuin-1 (SIRT1), a histone deacetylase enzyme expressed in ocular tissues with intracellular localization, plays a critical protective role against various degenerative ocular diseases. The link between reduced SIRT1 levels and diabetic retinopathy (DR) has prompted the exploration of natural therapeutic compounds that act as SIRT1 agonists. Curcumin (CUR), which has been shown to upregulate SIRT1 expression, is one such promising compound. However, effective delivery of CUR to the deeper ocular tissues, particularly the retina, remains a challenge due to its poor solubility and limited ocular penetration following topical administration. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for CUR topical ocular delivery represents a novel approach. Methods: In accordance with our prior research, optimized SNEDDS loaded with CUR were developed and characterized post-reconstitution with simulated tear fluid (STF) at a 1:10 ratio, showing suitable physicochemical and technological parameters for ocular delivery. Results: An entrapment efficiency (EE%) of approximately 99% and an absence of drug precipitation were noticed upon resuspension with STF. CUR-SNEDDS resulted in a better stability and release profile than free CUR under simulated ocular conditions. In vitro analysis of mucoadhesive properties revealed that CUR-SNEDDS, modified with a cationic lipid, demonstrated enhanced interactions with mucin, indicating the potential for improved ocular retention. Cytotoxicity tests demonstrated that CUR-SNEDDS did not affect the viability of human corneal epithelial (HCE) cells up to concentrations of 3 μM and displayed superior antioxidant activity compared to free CUR in an oxidative stress model using retinal pigment epithelial (ARPE-19) cells exposed to hydroquinone (HQ). Cell uptake studies confirmed an enhanced accumulation of CUR within the retinal cells following exposure to CUR-SNEDDS compared to neat CUR. CUR-SNEDDS, at lower concentrations, were found to effectively induce SIRT1 expression. Conclusions: The cytocompatibility, antioxidant properties, and enhanced cellular uptake suggest that these developed systems hold promise as formulations for the delivery of CUR to the retina. Full article

Ocular diseases affecting the anterior and posterior segments of the eye are major causes of global vision impairment. Curcumin, a natural polyphenol, exhibits anti-inflammatory, antioxidant, antibacterial, and neuroprotective properties, making it a promising candidate for ocular therapy. However, its clinical use is hindered by low aqueous solubility, poor bioavailability, and rapid systemic elimination. This review comprehensively highlights advances in curcumin delivery systems aimed at overcoming these challenges. Emerging platforms, including proniosomal gels, transferosomes, and cyclodextrin complexes, have improved solubility, permeability, and ocular retention. Nanoparticle-based carriers, such as hybrid hydrogels and biodegradable nanoparticles, enable sustained release and targeted delivery, supporting treatments for posterior segment diseases like diabetic retinopathy and age-related macular degeneration. For anterior segment conditions, including keratitis and dry eye syndrome, cyclodextrin-based complexes and mucoadhesive systems enhance corneal permeability and drug retention. Mechanistically, curcumin modulates key pathways, such as NF-κB and TLR4, reducing oxidative stress, angiogenesis, and apoptosis. Emerging strategies like photodynamic therapy and neuroprotective approaches broaden their application to eyelid conditions and neuroinflammatory ocular diseases. These advancements address curcumin’s pharmacokinetic limitations, supporting its clinical translation into ophthalmic therapies. This work underscores curcumin’s potential in ocular disease management and advocates clinical trials to validate its safety, efficacy, and therapeutic relevance. Full article

Neovascular glaucoma is a rare and serious condition typically associated with advanced ocular or systemic vascular diseases such as central retinal vein occlusion or diabetic retinopathy. This report describes a unique case of neovascular glaucoma presenting for the first time as an initial symptom of bilateral occlusive retinal vasculitis (ORV) in a generally healthy 4-year-old girl. The patient presented with symptoms of pain and redness in the left eye, accompanied by high intraocular pressure. These symptoms were particularly distressing and uncharacteristic for such a young child. Clinical examination revealed significant findings, including elevated intraocular pressure, corneal edema, and iris neovascularization in the left eye. Additional imaging studies, including fluorescein angiography, demonstrated extensive retinal ischemia with peripheral capillary nonperfusion, confirming the diagnosis of occlusive vasculitis. The management of this case was challenging due to the progressive and aggressive nature of the disease in a 4-year-old patient. This article aims to present the diagnostic and therapeutic strategies for the management of this condition. This report highlights a rare case of neovascular glaucoma as the first manifestation of bilateral ORV in a young child. The unusual presentation emphasizes the need for a high index of suspicion and comprehensive evaluation in cases of pediatric neovascular glaucoma. Early diagnosis and prompt, multimodal treatment are crucial in preventing irreversible vision loss in such cases. Full article

Background/Objectives: Diabetes is a well-recognised factor inducing a plethora of corneal alterations ranging from dry eye to reduced corneal sensibility, epithelial defects, and reduced cicatrisation. This cohort study aimed to assess the efficacy of a novel ophthalmic solution combining cross-linked hyaluronic acid (CHA), chondroitin sulfate (CS), and inositol (INS) in managing diabetes-induced corneal alterations. Specifically, it evaluated the solution’s impact on the tear breakup time (TBUT), the ocular surface disease index (OSDI), and corneal sensitivity after three months of treatment. Additionally, the solution’s potential to promote wound healing was examined. Methods: Two different populations were retrieved from the database; the first one was composed of 20 diabetic subjects treated for three months with the ophthalmic CAH-CS (OPHTAGON srl, Rome, Italy), while the second group was composed of 20 diabetic subjects who did not want to use any eye lubricant or other treatment. The outcome measures were the TBUT, the OSDI score, and the corneal sensitivity measured using a Cochet–Bonnet aesthesiometer. To investigate the wound-healing properties, in vitro tests were conducted using two cell lines, comparing the results of scratch tests with and without the solution. Results: The results indicate that CHA-CS significantly improved the tear film stability, as evidenced by an increased TBUT and a reduction in dry eye symptoms reflected by lower OSDI scores. Moreover, the solution was associated with an enhanced corneal sensitivity in treated patients. In wound-healing assays, CHA-CS promoted cell motility, suggesting a supportive role in tissue repair compared to untreated cells. Conclusions: Collectively, the results suggest that CHA-CS could serve as an innovative tool for the treatment of diabetic patients with corneal alterations and delayed corneal sensitivity. Clinical trial registration number: Clinical Trial.gov NCT06573606. Full article

Inflammatory bowel disease (IBD) is a complex, multisystemic disease and is associated with ocular pathology in 4–12% of patients. In general, ocular disease affects Crohn’s patients more frequently than those with ulcerative colitis. Episcleritis and uveitis are the most common presentations, with episcleritis often correlating with IBD flares, whereas uveitis presents independently of IBD activity and, in some cases, may even alert clinicians to a new diagnosis of IBD. Corneal EIMs encompass a range of pathologies, such as the common and benign keratoconjunctivitis sicca (dry eye disease), which nevertheless causes significant patient discomfort, and the rarer condition of peripheral ulcerative keratitis, which warrants urgent review due to the risk of corneal perforation. Alongside EIMs, clinicians should also be aware of the iatrogenic consequences to the eye following treatment of IBD. Corticosteroids may cause cataracts, glaucoma, and—indirectly via hyperglycaemia—diabetic retinopathy. Methotrexate is irritating to ocular tissues and may cause conjunctivitis and blepharitis. Biologic medications, such as anti-TNFα agents, overlap in their use as treatment of both IBD and uveitis, and yet in some patients may also increase the risk of acute uveitis flares, as well as opportunistic, sight-threatening infections. With integrated care between gastroenterology and ophthalmology, patient outcomes can be improved by facilitating earlier detection and management of ocular disease. This narrative review summarises the ocular extraintestinal manifestations of IBD, including pathophysiology, epidemiology, and current treatment strategies. Full article

Background: Internal ocular diseases, such as macular edema, uveitis, and diabetic macular edema require precise delivery of therapeutic agents to specific regions within the eye. However, the eye’s complex anatomical structure and physiological barriers present significant challenges to drug penetration and distribution. Traditional eye drops suffer from low bioavailability primarily due to rapid clearance mechanisms. Methods: The novel ocular drug delivery system developed in this study utilizes poly(lactic-co-glycolic acid) (PLGA) nanoparticles modified with cell-penetrating peptides (CPPs). In vitro drug release studies were conducted to evaluate the sustained-release properties of the nanoparticles. Ex vivo experiments using MDCK cells assessed corneal permeability and uptake efficiency. Additionally, in vivo studies were performed in rabbit eyes to determine the nanoparticles’ resistance to elimination by tears and their retention time in the aqueous humor. Results: In vitro drug release studies demonstrated superior sustained-release properties of the nanoparticles. Ex vivo experiments revealed enhanced corneal permeability and increased uptake efficiency by MDCK cells. In vivo studies in rabbit eyes confirmed the nanoparticles’ resistance to elimination by lacrimal fluid and their ability to extend retention time in the aqueous humor. CPP modification significantly improved ocular retention, corneal penetration, and cellular endocytosis efficiency. Conclusions: The CPP-modified PLGA nanoparticles provide an effective and innovative solution for ocular drug delivery, offering improved bioavailability, prolonged retention, and enhanced drug penetration, thereby overcoming the challenges of traditional intraocular drug administration methods. Full article

Background: Corneal degeneration is a form of progressive cell death caused by multiple factors, such as diabetic retinopathy. It is the most well-known neural degenerative disease caused by macular degeneration in the aged and those with retinitis pigmentosa. Myocardial infarction is becoming a more common burden, causing cardiomyocyte degeneration, ischemia, and heart tissue death. This study examined the preventive effects of rutin on isoproterenol (ISO)-induced oxidative damage (that is, inflammation) on rabbit corneal epithelial cells and mouse heart injuries. Methods: These investigations involved a cytotoxicity test, biochemical analysis, qRT-PCR, Western blotting, and mouse cardiac histopathology. Results: The results showed that rutin enhanced ADH7 and ALDH1A1, retinoic acid signaling components in SIRC1 rabbit corneal cell lines. The production of NO by ocular epithelial cells was significantly reduced. It reduced cTnT and cTnI, CK-MB, and LDH contents in mouse cardiac tissue. The nuclear expressions of Nrf2, Sirt, and HO-1 were all increased by rutin. Docking studies revealed a good interaction between rutin and the Keap protein, enhancing Nrf2 nuclear activity. Conclusions: This showed that rutin can potentially enhance ADH7 and ALDH1A1 corneal signaling components, preventing corneal degeneration and mitigating ISO-induced myocardial infarction (MI) via Keap/Nrf2 expressions. Full article

Penetrating keratoplasty (PK) is a corneal surgery that is employed to repair the full-thickness corneal lesion. This study aimed to survey the possible systemic risk factors of infectious keratitis after penetrating keratoplasty (PK) via the Taiwan National Health Insurance Research Database (NHIRD). A retrospective case–control study was conducted, and 327 patients who received the PK were enrolled after exclusion. The main outcome was the development of infectious keratitis, and people were divided into those with infectious keratitis and those without the outcome. Cox proportional hazard regression was conducted to produce adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of specific demographic indexes and systemic diseases on infectious keratitis. There were 68 patients who developed infectious keratitis after the whole follow-up period. The diabetes mellitus (DM) (aHR: 1.440, 95% CI: 1.122–2.874, p = 0.0310) and chronic ischemic heart disease (aHR: 1.534, 95% CI: 1.259–3.464, p = 0.0273) groups demonstrated a significant association with infectious keratitis. The DM group also revealed significant influence on infectious keratitis development in all the subgroups (all p < 0.05). Nevertheless, the effect of chronic ischemic heart disease on infectious keratitis was only significant on those aged older than 60 years (p = 0.0094) and both sexes (both p < 0.05). In conclusion, the presence of DM and chronic ischemic heart disease are associated with infectious keratitis after PK. However, local risk factors for infectious keratitis developed in those receiving PK had not been evaluated. Full article

This study aims to compare meibomian gland (MG) dropout and MG dysfunction (MGD) between patients with diabetes mellitus (DM) with moderate–severe non-proliferative diabetic retinopathy (NPDR) and patients with no diabetes (NDM). This prospective, transversal, age, and gender-matched case–control study included 98 DM and 106 NDM eyes. Dry eye disease (DED) and MGD evaluations were performed, including meibography (Keratograph 5M^®). The objective MG dropout percentage was obtained by analyzing meibography images with ImageJ software (v. 1.52o, National Institutes of Health, Bethesda, MD, USA) and was subsequently graded with Arita’s meiboscore. The DM duration was 18 ± 9 years. The mean meiboscore (3.8 ± 0.8 vs. 3.4 ± 1.0, p = 0.001), meiboscore severity (p = 0.016), and MG dropout (45.1 ± 0.1% vs. 39.0 ± 0.4%, p < 0.001) were greater in DM than in NDM. All patients showed MG dropout (meiboscore > 1). Lower eyelids showed greater MG dropout in both groups. A correlation with age (r = 0.178, p = 0.014) and no correlations with DM duration or gender (p > 0.005) were observed. Patients with diabetes showed greater corneal staining (1.7 ± 1.3 vs. 0.9 ± 1.1; p < 0.001), reduced corneal sensitivity (5.4 ± 1.1 vs. 5.9 ± 0.4; p < 0.001), lower MG expressibility (3. 9 ± 1.6 vs. 4.4 ± 2.1; p = 0.017), and worse meibum quality (1.9 ± 0.8 vs. 1.7 ± 0.5; p = 0.019). Tear breakup time, osmolarity, MMP-9, Schirmer, and the Ocular Surface Disease Index showed no significant differences. In conclusion, patients with DM with NPDR have greater MG dropout and meiboscore, as well as more severe MGD and DED parameters than persons with NDM. Full article

Background and Aim. To study the relationships of cardiovascular risk factors with cancer and cardiovascular mortality in a cohort of middle-aged men followed-up for 61 years. Materials and Methods. A rural cohort of 1611 cancer- and cardiovascular disease-free men aged 40–59 years was examined in 1960 within the Italian Section of the Seven Countries Study, and 28 risk factors measured at baseline were used to predict cancer (n = 459) and cardiovascular deaths (n = 678) that occurred during 61 years of follow-up until the extinction of the cohort with Cox proportional hazard models. Results. A model with 28 risk factors and cancer deaths as the end-point produced eight statistically significant coefficients for age, smoking habits, mother early death, corneal arcus, xanthelasma and diabetes directly related to events, and arm circumference and healthy diet inversely related. In the corresponding models for major cardiovascular diseases and their subgroups, only the coefficients of age and smoking habits were significant among those found for cancer deaths, to which healthy diet can be added if considering coronary heart disease alone. Following a competing risks analysis by the Fine–Gray method, risk factors significantly common to both conditions were only age, smoking, and xanthelasma. Conclusions. A sizeable number of traditional cardiovascular risk factors were not predictors of cancer death in a middle-aged male cohort followed-up until extinction. Full article

Diabetic retinopathy (DR) remains the leading cause of blindness in the working-age population. Its progression causes gradual damage to corneal nerves, resulting in decreased corneal sensitivity (CS) and disruption of anterior-eye-surface homeostasis, which is clinically manifested by increased ocular discomfort and dry eye disease (DED). This study included 52 DR patients and 52 sex- and age-matched controls. Ocular Surface Disease Index (OSDI) survey, tear film-related parameters, CS, and in vivo corneal confocal microscopy (IVCM) of the subbasal plexus were performed. Furthermore, all patients underwent tear sampling for neurotrophin and cytokine analysis. OSDI scores were greater in DR patients than in controls (p = 0.00020). No differences in the Schirmer test score, noninvasive tear film-break-up time (NIBUT), tear meniscus or interferometry values, bulbar redness, severity of blepharitis or meibomian gland loss were found. In the DR group, both the CS (p < 0.001), and the scotopic pupil diameter (p = 0.00008) decreased. IVCM revealed reduced corneal nerve parameters in DR patients. The stage of DR was positively correlated with the OSDI (Rs = +0.51, 95% CI: + 0.35–+0.64, p < 0.001) and negatively correlated with IVCM corneal nerve parameters and scotopic pupillometry (Rs = −0.26, 95% CI: −0.44–−0.06, p = 0.0097). We found negative correlations between the OSDI and IVCM corneal innervation parameters. The DR group showed lower tear film-brain-derived neurotrophic factor (BDNF) levels (p = 0.0001) and no differences in nerve growth factor (NGF)-β, neurotrophin (NT)-4, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-4, IL-5, IL-6, or IL-12 concentrations. Tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-10, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-γ levels were decreased among patients with DR. Corneal innervation defects have a direct impact on patients’ subjective feelings. The evolution of DR appears to be associated with corneal nerve alterations, emphasizing the importance of IVCM. Full article

Artificial intelligence (AI) has seen significant progress in medical diagnostics, particularly in image and video analysis. This review focuses on the application of AI in analyzing in vivo confocal microscopy (IVCM) images for corneal diseases. The cornea, as an exposed and delicate part of the body, necessitates the precise diagnoses of various conditions. Convolutional neural networks (CNNs), a key component of deep learning, are a powerful tool for image data analysis. This review highlights AI applications in diagnosing keratitis, dry eye disease, and diabetic corneal neuropathy. It discusses the potential of AI in detecting infectious agents, analyzing corneal nerve morphology, and identifying the subtle changes in nerve fiber characteristics in diabetic corneal neuropathy. However, challenges still remain, including limited datasets, overfitting, low-quality images, and unrepresentative training datasets. This review explores augmentation techniques and the importance of feature engineering to address these challenges. Despite the progress made, challenges are still present, such as the “black-box” nature of AI models and the need for explainable AI (XAI). Expanding datasets, fostering collaborative efforts, and developing user-friendly AI tools are crucial for enhancing the acceptance and integration of AI into clinical practice. Full article

Diabetes mellitus (DM) is one of the most prevalent diseases globally, and its prevalence is rapidly increasing. Most patients with a long-term history of DM present with some degree of keratopathy (DK). Despite its high incidence, the underlying inflammatory mechanism of DK has not been elucidated yet. For further insights into the underlying immunopathologic processes, we utilized streptozotocin-induced mice to model type 1 DM (T1D) and B6.Cg-Lepob/J mice to model type 2 DM (T2D). We evaluated the animals for the development of clinical manifestations of DK. Four weeks post-induction, the total frequencies of corneal CD45⁺CD11b⁺Ly-6G⁻ myeloid cells, with enhanced gene and protein expression levels for the proinflammatory cytokines TNF-α and IL-1β, were higher in both T1D and T2D animals. Additionally, the frequencies of myeloid cells/mm² in the sub-basal neural plexus (SBNP) were significantly higher in T1D and T2D compared to non-diabetic mice. DK clinical manifestations were observed four weeks post-induction, including significantly lower tear production, corneal sensitivity, and epitheliopathy. Nerve density in the SBNP and intraepithelial terminal endings per 40x field were lower in both models compared to the normal controls. The findings of this study indicate that DM alters the immune quiescent state of the cornea during disease onset, which may be associated with the progressive development of the clinical manifestations of DK. Full article