Search Results (101)

Background/Objectives: The purpose of this study was to clinically characterize the lacrimal functional unit (LFU) of patients with chronic ocular pain associated with dry eye disease (DED). Methods: Ninety-three participants were included in this cross-sectional study: 28 patients with chronic ocular pain associated with DED (pain-DED), 35 patients with DED but no pain (no pain-DED), and 30 subjects without DED or ocular pain (controls). The following examinations were performed: symptom questionnaires, visual function assessment, tear meniscus, ocular surface evaluation, meibography, corneal sensitivity, Schirmer test, and in vivo corneal confocal microscopy. Results: Both DED groups presented increased DED-related symptoms (p < 0.001), corneal staining (p < 0.001), Meibomian gland loss (p < 0.010), and dendritic cell density (p < 0.001) compared with controls. Comparing both DED groups, the pain-DED group showed higher DED-related symptoms (p < 0.002) and increased microneuroma density (p < 0.001). Additionally, significant positive correlations were observed between symptom questionnaires and corneal staining (vs. OSDI: r = 0.514, p < 0.001; vs. m-SIDEQ: r = 0.504, p < 0.001; vs. NRS: r = 0.361, p < 0.001; vs. WBFPRS: r = 0.317, p = 0.002), dendritic cell density (vs. OSDI: r = 0.429, p < 0.001; vs. m-SIDEQ: r = 0.440, p < 0.001), and microneuroma density (vs. NRS: r = 0.405, p < 0.001; vs. WBFPRS: r = 0.416, p < 0.001). Conclusions: Differences in the LFU, especially in the morphology of sub-basal corneal nerves, are related to the presence of DED and chronic ocular pain and, along with ocular clinical questionnaires, can help phenotype these patients. Full article

Background/Objectives: Painful diabetic peripheral neuropathy (pDPN) significantly impacts quality of life, yet its diagnosis remains challenging due to reliance on subjective pain reports and limited objective biomarkers. This meta-analysis evaluated corneal nerve morphology parameters; corneal nerve fibre length (CNFL), corneal nerve fibre density (CNFD), and corneal nerve branch density (CNBD), measured through in vivo confocal microscopy (IVCM), as potential tools for differentiating painful and painless forms of diabetic neuropathy. Methods: A systematic review was performed comparing corneal nerve morphology across four groups: painful diabetic neuropathy (pDPN), non-painful diabetic neuropathy (npDPN), diabetes without neuropathy (DPN-), and healthy controls. Literature search extended over MEDLINE, EMBASE, Web of Science, and Cochrane Library, focusing on studies published since 2000. Study quality was assessed using the Newcastle–Ottawa Scale, while evidence certainly followed GRADE guidelines. Random-effects meta-analyses calculated mean differences (MDs) with 95% confidence intervals (CIs) for CNFL, CNFD, and CNBD. Results: Seven observational studies comprising 803 participants (213 pDPN, 275 npDPN, 99 DPN-, and 216 controls) revealed no significant differences between pDPN and npDPN groups in CNFL (MD = 0.79, 95% CI −0.64 to 2.22), CNFD (MD = 1.67, 95% CI −0.14 to 3.47), or CNBD (MD = 1.84, 95% CI −4.31 to 7.98). However, all metrics were markedly reduced in pDPN compared to DPN- and healthy controls. Conclusions: While effective in identifying diabetic neuropathy, common corneal nerve morphology parameters cannot reliably distinguish pDPN from npDPN. This highlights the need for research into mechanisms like central sensitization, inflammation, and micro-neuromas, which could refine diagnostic and therapeutic approaches for pDPN. Full article

Background: Sjögren’s syndrome (SS) is a systemic autoimmune condition marked by significant dry eye disease (DED), leading to considerable corneal changes. These modifications, encompassing punctate epithelial erosions, chronic epithelial abnormalities, and corneal ulcers, significantly impact eyesight and quality of life. Progress in comprehending the corneal pathophysiology associated with SS has prompted innovative diagnostic and treatment approaches. Aim: This narrative review aims to examine developing trends in the pathogenesis, diagnostic methods, and treatment strategies for Sjögren’s syndrome-associated corneal changes. Methods: The study was based on a narrative review of the current literature available on PubMed and Cochrane from Jan 2000 to December 2024. Results: Corneal changes associated with Sjögren’s syndrome result from a multifactorial interaction of ocular surface inflammation, tear film instability, and epithelium degradation. Recent research underscores the significance of immune-mediated pathways, such as T-cell-induced inflammation and cytokine dysregulation, as crucial factors in corneal disease. Innovations in diagnostic instruments, including in vivo confocal microscopy and tear proteomics, provide earlier and more accurate identification of subclinical alterations in the corneal epithelium and stroma. Therapeutic developments concentrate on meeting the specific requirements of SS-related DED. Biological treatments, especially tailored inhibitors of interleukin-6 and tumor necrosis factor-alpha, show potential in mitigating inflammation and facilitating epithelial repair. Moreover, regenerative approaches, such as autologous serum tears and mesenchymal stem cell therapies, provide innovative methods to repair ocular surface integrity. Advanced drug delivery technologies, including nanoparticle-loaded eye drops, enhance bioavailability and therapeutic efficacy. Conclusion: Recent developments in comprehending SS-related corneal changes have transformed the management approach to precision medicine. The combination of improved diagnostics and innovative therapy approaches offers potential for reducing disease progression, maintaining corneal health, and enhancing patient outcomes. Subsequent investigations ought to concentrate on enhancing these tactics and examining their long-term safety and effectiveness. Clinicians and researchers must adopt these developments to successfully tackle the difficulties of SS-related corneal illness, providing hope for improved care and higher quality of life for those affected. Full article

Neurotrophic keratopathy (NK) is a rare degenerative disease caused by impairment of the trigeminal nerve, leading to corneal anesthesia, epithelial breakdown, and progressive vision loss. Conventional treatments primarily focus on symptom management and the prevention of complications, but they do not address the underlying nerve dysfunction. Corneal neurotization (NT) has emerged as a promising surgical intervention aimed at restoring corneal sensation and improving ocular surface homeostasis. This review evaluates the outcomes of corneal neurotization in patients with NK and compares the effectiveness of direct (DNT) and indirect (INT) techniques. Studies have reported significant improvements in corneal sensitivity, with success rates ranging from 60.7% to 100% (mean: 90%). Most patients experienced recovery of corneal sensation, as measured by the Cochet–Bonnet aesthesiometer, with no significant differences in outcomes between DNT and INT. Indirect neurotization using a sural nerve graft was the most commonly employed technique (63% of cases), while the use of acellular allografts demonstrated comparable efficacy and simplified the procedure. Postoperative corneal sensitivity increased significantly, from a preoperative average of 2.717 mm to 36.01 mm, with reinnervation typically occurring within 4–6 months and peaking at 12 months. In vivo confocal microscopy confirmed the presence of nerve regeneration. Neurotization was found to be safe, with minimal donor-site complications, which generally resolved within one year. Although the procedure improves corneal sensation and tear film stability, visual acuity outcomes remain variable due to pre-existing corneal damage. Early intervention is, therefore, recommended to prevent irreversible scarring. However, the number of patients undergoing the procedure remains limited, making it difficult to draw definitive conclusions. Most available studies consist of small case series. Further research with larger sample sizes is needed to refine surgical techniques and optimize patient selection, thereby improving outcomes in the management of NK. Full article

Background and Clinical Significance: Acanthamoeba keratitis (AK) is a rare but serious corneal infection that can lead to severe visual impairment or blindness if not promptly treated. The condition is primarily associated with contact lens use but can also occur due to ocular trauma or environmental contamination. The most frequently used treatment options include biguanides and diamidines, though dosing protocols remain empirical and vary widely among clinicians. Recent research has explored a new standardized protocol with 0.08% polihexanide (polyhexamethylene biguanide, PHMB) as a monotherapy for AK, offering improved efficacy and better corneal penetration. Case Presentation: This case report describes a 35-year-old female contact lens wearer who presented with redness, pain, photophobia, and vision loss in her right eye. Upon referral, a slit-lamp examination revealed stromal infiltrates and perineural involvement, with in vivo confocal microscopy (IVCM) confirming Acanthamoeba cysts. The patient was treated with a new standardized intensive regimen of polihexanide 0.08% monotherapy, leading to rapid clinical improvement. Corneal infiltrates were significantly reduced, and the best-corrected visual acuity (BCVA) improved from 0.4 logMAR to 0.15 logMAR. Resolution with only discrete stromal haze was achieved over the following months, without recurrence. Conclusions: This case highlights the potential of polihexanide 0.08% monotherapy as an effective treatment for AK in a new standardized treatment protocol. 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/Objectives: Blepharitis is a condition often caused by Demodex folliculorum infestations, resulting in significant ocular discomfort and surface damage. Current treatments offer only temporary relief and fail to eliminate mites effectively. This study evaluates nano-niclosamide (nano-NCL), a lipophilic nanosuspension designed to enhance solubility and permeability, for targeting Demodex folliculorum. Methods: Nano-NCL was characterized by particle size, zeta potential, transmission electron microscopy, pH measurement, bacterial culture, and HPLC. Viable Demodex mites were collected from patients’ eyelashes and assigned to six treatment groups: DDW, F127, 0.15% nano-NCL, 0.3% nano-NCL, 20% TTO, and Okra. Mite survival was analyzed using Kaplan–Meier curves. The ocular surface safety was assessed via slit-lamp examination, corneal fluorescein staining, and in vivo confocal microscopy. Results: The nano-NCL particles are uniformly rod-shaped, approximately 291 nm in size, and exhibit good stability, remaining suspended in various media for up to 20 days. The formulation has a stable pH of 6 and demonstrated no bacterial growth, indicating sterility and suitability for clinical use. In vitro, both 0.15% (w/v) and 0.30% (w/v) nano-NCL significantly reduced Demodex survival, with mortality rates ranging from 70.6% to 92.3% within 2 h. Safety evaluations showed minimal corneal staining and inflammation. Notably, 0.15% nano-NCL displayed efficacy comparable to that of 20% tea tree oil (TTO) and Okra, which are established anti-Demodex treatments. Conclusions: Nano-NCL, particularly at 0.15%, rapidly eliminates mites while maintaining excellent ocular tolerability, making it a promising treatment for Demodex-related ocular surface diseases. Full article

Background Despite many studies on polymer-incorporated nanocarriers for ophthalmic drug delivery, few have thoroughly explored the relationship between coating composition and performance. This study aimed to evaluate the effects of three commonly used cationic polymers—distearoyl phosphatidylethanolamine-polyethylene glycol 1000-poly(amidoamine) (DSPE-PEG1000-PAMAM), trimethyl chitosan (TMC), and (2,3-dioleoyloxypropyl) trimethylammonium chloride (DOTAP)—on the corneal behaviors and anti-cataract efficacy of diosmetin (DIO)-loaded micelles (D-M-P, D-M-T, and D-M-D, respectively). Methods The DIO-loaded micelles were prepared using the thin-film dispersion method and incorporated with the three polymers through hydrophobic interactions and electrostatic adsorption. Structural characterization was demonstrated by TEM imaging and particle size analyzer. In vitro release behavior was detected by the dialysis method. Cell viability of D-M-P, D-M-T, and D-M-D on L929 cells was detected by CCK-8 assays, with cellular uptake performed using coumarin 6 as the fluorescence indicator. Precorneal retention behaviors of these three vesicles were observed by In Vivo Imaging System. Transcorneal permeability was determined by modified Franz diffusion method and the permeation routes of the vesicles are investigated. Selenite-induced cataract model was established. The anti-cataract effects of three different DIO-loaded micelles were evaluated by the observation of lens opacity and antioxidant enzyme activities. Eye Irritation of the DIO in different preparations was estimated using the Draize test, along with H&E staining of the corneas. Results Structural characterization of DIO-loaded micelles revealed that the vesicles were spherical, with a uniform size distribution of around 28 nm, a similar surface potential of approximately 6.0 mV, and a high DIO entrapment efficiency of about 95%. Compared to the DIO suspension, all three formulations exhibited a significant sustained-release effect. They showed no signs of irritation and demonstrated increased IC50 values in L929 cells, indicating improved biocompatibility. Cellular uptake in human lens epithelial cells (HLECs) was assessed using confocal laser scanning microscopy. C-M-T displayed the highest fluorescence signals, with a cellular internalization 3.2 times greater than that of the solution group. Both C-M-T and C-M-P enhanced vesicle retention on the corneal surface by at least 47.8% compared to the Cou-6 solution. Furthermore, TMC facilitated the paracellular transport of vesicles into the deepest layers of the cornea and delivered DIO across the cornea, with a P_app value 3.11 times and 1.49 times those of D-M-D and D-M-P, respectively. In terms of therapeutic efficacy, D-M-T demonstrated the most significant attenuation of lens opacity, along with enhanced antioxidant enzyme activities and inhibition of lipid peroxidation. Conclusion The modification of micelle vesicles with different cationic polymers significantly influences their performance in ocular drug delivery. Among the tested formulations, D-M-T stands out due to its multiple advantages, including enhanced transcorneal drug delivery, therapeutic efficacy for DIO, and safety, making it the most promising candidate for ophthalmic applications. Full article

Background/Objectives: to report a novel KRT3 Meesmann corneal dystrophy (MECD) mutation and its clinical findings in a Spanish family, thus completing the international database. Case series study. Methods: Two generations of three family members were studied. The clinical ophthalmologic evaluation was made including best-corrected visual acuity (BCVA), biomicroscopy with and without fluorescein, fundoscopy, Schirmer test I, non-invasive break-up time (NiBUT), and esthesiometry. In vivo confocal microscopy (IVCM), anterior segment optical coherence tomography (AS-OCT) with an epithelial map, and genetic analysis were also performed. Results: A novel heterozygous mutation in the KRT3 gene c.1527G>T (p. Glu509Asp) was identified. Biomicroscopy revealed bilateral multiple corneal intraepithelial cysts. IVCM showed numerous and relatively small microcysts (12–32 µm), hyperreflective materials, subepithelial nerve and Bowman’s layer alterations. AS-OCT scan revealed diffuse hyperreflectivity and the epithelial map displayed thickening of the corneal epithelium in the interpalpebral zone (proband: 52–68 µm and father’s proband: 55–71 µm) with a slightly thinned cornea. Conclusions: We identified a new mutation in the KRT3 gene–c.1527G>T (p. Glu509Asp) in a Spanish family with MECD. A comprehensive characterization of the clinical signs, using different techniques, especially an epithelial map, could be useful to diagnose and monitor epithelial changes by quantitative measures. Epithelial map changes provide better understanding of MECD differential epithelial behavior and its progression changes. Larger studies will be necessary to better understand these specific patterns and clinically evaluate new therapies. Full article

Background/Objectives: In this study, we aim to evaluate in vivo confocal microscopy (IVCM) findings of corneal stromal dystrophies (CSDs) including granular, macular and lattice corneal dystrophy that can be used for differential diagnosis and monitoring recurrences after surgical interventions. Methods: Patients diagnosed with CSD who were followed-up in the cornea and ocular surface unit were included in this study. IVCM was performed using the Heidelberg Retina Tomograph 3, Rostock Cornea Module (Heidelberg Engineering, Germany) and anterior segment optical coherence tomography (AS-OCT) imaging was performed using the Spectralis OCT (Heidelberg Engineering, Germany). The morphological structure, size and location of deposits, epithelial involvement and presence of inflammatory and dentritic cells were compared among the three stromal dystrophies. Results: A total of 72 eyes from 36 participants were included in this study. Twelve patients (33.33%) had granular corneal dystrophy (GCD), ten (27.77%) had macular corneal dystrophy (MCD) and fourteen (38.88%) had lattice corneal dystrophy (LCD). In GCD, highly reflective deposits varying in size (20 µm–300 µm) were observed. In MCD, diffuse hyperreflective stroma with dark striae, dentritic cells around deposits and abnormal keratocytes were observed. In LCD, there were branching, lattice-like and granular deposits with epithelial cell disruption in some of the eyes. In MCD, the central corneal thickness was thinner (449.44 ± 65.45 µm) compared to GCD and LCD (565.16 ± 49.62 µm and 569.91 ± 39.32 µm p < 0.001). Recurrence was observed in five patients following penetrating keratoplasty. Conclusions: IVCM is a valuable tool for distinguishing CSD subtypes and monitoring recurrence following surgical interventions. Full article

Reflective confocal imaging systems often face challenges in achieving high resolution, imaging speed, and uniformity, particularly for reflective sample imaging. This study introduces a reflective multi-point confocal imaging system designed to improve imaging speed, expand the field of view, and optimize performance for reflective sample imaging using incoherent, telecentric light-emitting diode (LED) illumination. By integrating uniform illumination with microlens arrays and optimizing instantaneous structured illumination microscopy optical components, the system achieves a resolution of 1116 lp/mm (20×, 0.42), 100 fps imaging, and a 500 µm × 500 µm field of view while improving contrast. A comparative analysis of laser- and LED-based scanning demonstrates that incoherent illumination provides superior uniformity and reduces intensity variance in reflective imaging. Validation through photon-reassignment experiments, resolution target imaging, and 100 nm metal particle visualization confirmed the system’s enhanced resolution. Furthermore, ex vivo corneal imaging revealed cellular-level details, suggesting its potential for noncontact corneal diagnostics. Full article

Purpose: Our aim was to investigate risk factors, clinical characteristics, and antibiotic susceptibility patterns of cornea-isolated Streptococcus species collected at a tertiary hospital in China over 18 years. Methods: This retrospective study reviewed data from 350 patients diagnosed with Streptococcal keratitis at Beijing Tongren Hospital between January 2006 and December 2023, including demographics, risk factors, clinical signs, in vivo confocal microscopy (IVCM) imaging, and antibiotic susceptibility testing. Results: The predominant type was Streptococcus pneumoniae (n = 108, 29.8%), followed by Streptococcus mitis (n = 90, 24.9%) and Streptococcus oralis (n = 85, 23.5%). Main risk factors included previous ocular surface disease (24.6%), ocular surgery (21.4%), and trauma (16.3%). Significant differences in clinical characteristics were observed among S. pneumoniae, S. oralis, and S. mitis regarding infiltration location (p = 0.038) and size (p = 0.037), as well as hypopyon presence (p = 0.006). IVCM revealed deeper inflammatory cell distribution and structural disruption as the disease progressed. Resistance rates of aminoglycosides, β-lactams, and fluoroquinolones have increased, with significant differences among species for amikacin (p = 0.010), gentamicin (p = 0.007), and others. Poor outcomes correlated with disease duration over one month, central corneal ulcers, dense infiltrations, hypopyon, and scar tissue presence on IVCM. Conclusions:Streptococcal keratitis is a complex ocular infection with multiple risk factors. S. pneumoniae, S. mitis, and S. oralis are the primary causative agents, exhibiting varying clinical features and antibiotic resistance patterns. Key factors associated with poor outcomes include long disease duration, central corneal ulcers, and severe infiltration. Full article

Background: Diseases in humans caused by amphizoic amoebae that can result in visual impairment and even blindness, have recently been identified more frequently worldwide. Etiologically complex incidents of keratitis, including those connected with Acanthamoeba strains detected in Poland, were evaluated in this study. Methods: Corneal samples from cases resistant to antimicrobial therapy assessed for epidemiological, microbiological and parasitological aspects were investigated by phase-contrast microscope, slit lamp and by confocal microscopy. In vitro techniques were applied for detection of bacteria and fungi, and corneal isolates cultured under axenic condition using BSC medium—for detection of Acanthamoeba spp.; molecular techniques were applied for amoeba species identification. Results: Most etiologically complicated keratitis cases, detected in ~84% of incidents, was due to exposure of contact lenses to tap water or pool water; trophozoites and cysts of Acanthamoeba, concomitant bacteriae, e.g., Pseudomonas aeruginosa, fungi and microfilariae were identified in contact lens users. Conclusions: In samples from contact lens wearers where microbial keratitis is identified along with some connection with the patient’s exposure to contaminated water environments, a risk of Acanthamoeba spp. infections should be considered. Understanding the complicated relationship between Acanthamoeba spp., co-occurring pathogens including associated endosymbionts is needed. In vivo confocal microscopy and in vitro cultivation were necessary to identify potentially contagious concomitant factors affecting the complex course of the keratitis. Full article

Background/Objectives: The objective of this study was to examine the morphological corneal changes and outcomes following the implantation of an artificial endothelial layer (EndoArt) in patients with chronic corneal oedema. Methods: A systematic review of the literature was conducted alongside a detailed analysis of two clinical cases with chronic corneal oedema that were treated using EndoArt. Our experience with these two cases is included to provide practical insights and real-world outcomes. Results: Across the 24 cases reported (including the two presented here), an analysis was possible in 23 cases. Notably, 82% of patients had undergone at least one previous corneal transplant, with 39% having undergone three or more transplants. Additionally, 78% of cases had ocular comorbidities, with glaucoma surgery being the most prevalent (83%), which could have impacted visual outcomes. The follow-up period ranged from 3 to 17 months with a median of 3 months. After EndoArt implantation, the average reduction in the central corneal thickness (CCT) was 29%, and the rebubbling rate was 47.8%, with some cases requiring no rebubbling, while others required it up to 100% of the time. Visual acuity significantly improved from a mean best-corrected visual acuity (BCVA) value of 1.61 ± 0.5 logMAR to 1.07 ± 0.59 logMAR (p < 0.001). The CCT decreased from 771 ± 146 µm to 580 ± 134 µm (p < 0.001). These findings are consistent with our experience. Conclusions: EndoArt shows promise as an alternative treatment for chronic corneal oedema in complex cases where conventional corneal transplantation has failed or carries a high risk of failure. The morphological changes observed using anterior segment optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM) were similar to those reported after endothelial keratoplasty, with the notable exception of the absence of the hyper-reflective donor–host interface. Full article

The eye, and the cornea in particular, is a common site of chemotherapy induced toxicity, and ocular side effects of both traditional and novel agents have been reported. Corneal confocal microscopy (CCM) is an in vivo technique that allows for the study of all the corneal layers in an easy, non-invasive and reproducible way via the direct visualization of corneal cell morphologies as well as of sub-basal nerve plexus. Thus, it represents a useful way to identify and monitor chemotherapy induced corneal alterations. This work aims to review the use of CCM in identifying corneal toxicity secondary to chemotherapy treatment, as regards both corneal nerves alterations in the setting of chemotherapy induced peripheral neuropathy (CIPN) and other corneal structure changes, particularly involving the corneal epithelium. Full article