Search Results (59)

Objectives: To analyze changes in ocular dendritic cells and their correlation with signs of keratitis in patients with herpes simplex stromal keratitis (HSK) using in vivo confocal microscopy (IVCM). Methods: This was a retrospective, cross-sectional, controlled, single-center study. Fifty-nine eyes from 59 patients with HSK and 40 eyes from 40 control subjects were studied. Each patient underwent IVCM and slit-lamp examinations. The density, area, size, and number of dendritic cells (DCs) in the corneas of both groups were analyzed. The severity of HSK was assessed, and the morphology and density of DCs in the cornea in the HSK group, categorized by ocular parameter severity levels, were compared with those in the control group. Results: DC density was significantly greater in patients with HSK than in controls. The DC field and size and the number of branches were also significantly greater in the HSK group. Furthermore, the DC density increased and morphological changes were exacerbated with increasing degree of corneal edema. The DC density was significantly increased and morphological changes were significantly exacerbated in the HSK group compared to the control group, even in those with the mildest cases of HSK. Conclusions: DC density and morphological changes correlate with the degree of corneal edema in patients with HSK. Changes in DC density and morphology can be observed even in mild cases of HSK. IVCM may be a powerful tool for monitoring ocular surface immune responses in patients with HSK, aiding in the clinical diagnosis and management of this disease. Full article

Cytomegalovirus (CMV) infection of the anterior segment is increasingly recognized as an important cause of corneal endotheliitis and secondary glaucoma, even in immunocompetent individuals. CMV corneal endotheliitis typically presents with coin-shaped or linear keratic precipitates (KPs), corneal edema, mild anterior chamber inflammation, and recurrent intraocular pressure (IOP) elevation; persistent or episodic ocular hypertension may progress to glaucomatous optic neuropathy if inadequately treated. Definitive diagnosis relies on aqueous humor polymerase chain reaction (PCR) testing for CMV DNA, supported by adjunctive imaging including specular microscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). Management requires a comprehensive strategy integrating antiviral therapy, anti-inflammatory treatment, and appropriate IOP control. Topical or systemic ganciclovir remains the cornerstone, while refractory disease may necessitate surgical intervention. Older age and male sex, host immune status, prolonged or recurrent CMV infection, and pre-existing ocular conditions are major risk factors for progression and poor outcomes. The pathogenesis of secondary glaucoma is thought to involve both direct viral cytopathic effects and inflammation-mediated damage to the trabecular meshwork (TM), resulting in impaired aqueous outflow. Therefore, early recognition, accurate diagnosis, and effective treatment are essential to prevent corneal decompensation and permanent vision loss. Full article

Objectives: To assess diurnal changes, topographical differences, and day-to-day repeatability of ocular surface epithelial immune cell (EIC) density and morphology in dry eye disease (DED). Methods: Sixteen participants with moderate-to-severe DED (mean (SE) age 49.4 (4.2) years) underwent in vivo confocal microscopy at three timepoints (day-1 morning and evening and day-2 morning) at six locations: central cornea, inferior whorl, inferior cornea, and temporal cornea, limbus and conjunctiva. Diurnal and topographical variation in EIC density and morphology were analyzed using linear mixed-effects models with adjusted pairwise comparisons. Day-to-day repeatability was assessed using the coefficient of repeatability (CoR) for density and Cohen’s kappa for morphology. Results: EIC density and morphology varied by location (p < 0.001) but not by timepoint at any location (p = 0.59–0.90). Density was highest at the inferior cornea (model-estimated mean: 101.2 (SE: 21.7) cells/mm²) and temporal limbus (104.3 (22.7) cells/mm²), and lowest at the central cornea (26.8 [5.1] cells/mm² and inferior whorl (38.3 [8.2] cells/mm²; all pairwise, p < 0.001). EICs with large bodies were more frequent in conjunctiva (100%), inferior cornea (94%), and temporal cornea (87%), than in central cornea (34%) and whorl (19%) (all p ≤ 0.007). EICs with dendrites, and with long dendrites were similarly distributed (p < 0.001). Bland–Altman analysis showed low mean bias and EIC density was more repeatable at the central (CoR ± 23.8 cells/mm²) and temporal cornea (±27.5 cells/mm²) than the inferior cornea (±47.9 cells/mm²) or temporal conjunctiva (±42.3 cells/mm²). Morphology agreement was substantial to near-perfect (κ = 0.71–0.97). Conclusions: In DED, EIC density and morphology are diurnally stable and maintain topographic distribution patterns similar to healthy eyes. Day-to-day repeatability show location dependent patterns. The study provides feasibility data for using IVCM for EIC metrics in disease monitoring. Full article

Background/Objectives: During cataract surgery, topical anesthesia is routinely achieved through the instillation of topical anesthetic eye drops, while different agents may be applied to the corneal surface during the procedure to support lubrication and protection. The impact of these intraoperative strategies on corneal integrity and postoperative ocular surface recovery remains an area of clinical interest. This study aimed to compare the intraoperative and postoperative effects of applying a topical anesthetic gel (Ophtesic, Horus Pharma) on the corneal surface versus the use of balanced salt solution (BSS) during cataract surgery. Methods: In this longitudinal, observational prospective study, 24 eyes of 24 patients undergoing phacoemulsification received either topical anesthetic gel (n = 15) or BSS irrigation (n = 9). Central corneal thickness (CCT) and epithelial thickness were measured preoperatively and on postoperative days 1, 5, and 15 using anterior segment optical coherence tomography (AS-OCT). Basal epithelial cell (BEC) density was assessed by in vivo confocal microscopy (IVCM), while OSDI score, non-invasive breakup time (NI-BUT), and Schirmer test I values were evaluated preoperatively and on postoperative days 5 and 15. Patient and surgeon satisfaction were rated using a Likert-like scale. Results: Both groups showed increased CCT and epithelial thickness at day 1. In the gel group, CCT returned to baseline by day 15 (p = 0.361), and epithelial thickness normalized by day 5 (p = 0.066). In the BSS group, CCT remained elevated at day 15 (p < 0.05), and epithelial thickness decreased at day 5 (p < 0.05) before returning to baseline. BEC density normalized at day 15 in the gel group (p = 0.107) but remained altered in the BSS group (p < 0.05). NI-BUT Schirmer I, and OSDI showed a trend toward faster recovery in the gel group than in the BSS group. Conclusions: In this exploratory study, intraoperative application of a topical anesthetic gel appeared to support early normalization of corneal and tear film parameters while providing effective anesthesia. Further studies are warranted to confirm these observations and evaluate potential long-term benefits. Full article

Background: To assess longitudinal changes in the in vivo confocal microscopy (IVCM) features during Acanthamoeba keratitis (AK) treatment and develop a prognostic model. Methods: This retrospective study included 59 AK patients who underwent IVCM at baseline and 1 and 3 months. Fourteen morphological features covering pathogen-related characteristics, cyst arrangement patterns, and inflammatory markers were compared between good and poor prognosis groups, which were defined based on clinical outcomes including corneal perforation, the need for therapeutic keratoplasty, or final best-corrected visual acuity (BCVA) ≤ 0.05. Prognostic modeling was performed exclusively using baseline IVCM features and applied univariable and Firth-corrected multivariable logistic regression with collinearity assessment and clinical filtering, followed by 5-fold cross-validation. Results: Among 59 AK patients, 45 (76.3%) had a good prognosis and 14 (23.7%) had a poor prognosis. Poor prognosis eyes showed a higher prevalence of double-walled cysts, trophozoites, and clustered cysts, along with higher cyst density and deeper stromal invasion. In contrast, good-prognosis eyes had more target-like cysts, immature dendritic cells, and mature dendritic cells. Clustered cysts independently predicted poor prognosis (OR = 2.98), whereas target-like cysts (OR = 0.26) and mature dendritic cells (OR = 0.37) were protective (AUC = 0.883; all p < 0.05). Conclusions: IVCM provides a quantitative tool for early outcome prediction and individualized management. Higher cyst burden, clustered cysts, and persistent stromal involvement indicated poorer prognosis, whereas target-like cysts and mature dendritic cells indicated better prognosis. Full article

Artificial intelligence (AI) has been explored as a promising diagnostic aid for ocular surface diseases (OSDs). The spectrum of OSD ranges from highly prevalent benign conditions such as dry eye disease (DED) to rare but potentially dangerous disorders, including ocular surface squamous neoplasia (OSSN) and conjunctival melanoma. This review provides an overview of current applications of AI across the major categories of ocular surface pathology and specifically highlights anterior segment imaging modalities, including slit-lamp examination, optical coherence tomography (OCT), and in vivo confocal microscopy (IVCM). Meibography, tear film dynamics, biochemical profiling, and other DED-related measures are also examined. Across these domains, reported AI model performance matches or exceeds that of ophthalmologists, offering consistent, reproducible, and accurate approaches for guiding diagnosis. However, studies with limited external or prospective validation, variable labeling strategies, and small, device-specific datasets predominate in the current literature, thereby limiting generalizability. Large multicenter datasets, standardized diagnostic frameworks, multimodal integration, and prospective trials that assess human–AI cooperation in practical settings should be an emphasis in future research. By filling these gaps, AI systems could advance from experimental tools to clinically reliable applications that improve access and diagnostic accuracy in the care of ocular surface disease and tumors. Full article

Corneal nerves (CNs) are essential to maintain corneal epithelial integrity and ocular surface homeostasis. In vivo confocal microscopy (IVCM) enables the acquisition of high-resolution visualization of CNs, allowing visualization on a microscopic level. Traditionally, CN images must be analyzed by manual examination, which is time consuming and labor intensive. Artificial intelligence (AI) has facilitated reliable analysis of CN parameters, allowing for automatic and semiautomatic analysis of CNs. These include the identification, segmentation, and quantitative analysis of various CN parameters. This review summarizes the applications of AI-driven, automatic, and semiautomatic models in the CN analysis of IVCM images while also focusing on their diagnostic relevance in dry eye disease (DED) and neuropathic corneal pain (NCP). Recent advancements in AI have transformed IVCM image analysis by improving reproducibility and reducing operator dependency and time. The AI-based algorithm has been demonstrated to have good performance and sensitivity to identify and quantify the CN metrics. AI has also been utilized to improve the diagnostic accuracy of DED with IVCM scans, involving multiple portions of the CNs, such as the inferior whorl region. When employed with IVCM images of patients with NCP, AI-assisted identification of microneuromas and changes in CN metrics has provided an improvement in diagnostic accuracy. Despite promising advances and outcomes, the widespread implementation of these AI models in CN image analysis requires large-scale validation. Future integration of multimodal AI algorithms remains a promising endeavor to enhance diagnostic accuracy and disease stratification. Full article

Emerging evidence highlights the critical role of corneal nerves in the pathophysiology of dry eye disease (DED) and other related ocular surface disorders (OSDs). These conditions increasingly demonstrate neuropathic and neurotrophic components, wherein alterations in corneal nerve morphology and function contribute to symptomatology and disease progression. Recent advances in imaging and diagnostic modalities have enabled detailed, in vivo evaluation of corneal nerve architecture and sensory function, offering novel insights into underlying mechanisms and therapeutic responses. This review comprehensively examines current and emerging technologies for corneal nerve assessment, both structural and functional. The structural methods include in vivo confocal microscopy (IVCM), optical coherence tomography (OCT)-based nerve imaging (e.g., micro-OCT), and emerging technologies like multiphoton microscopy. The functional methods of corneal nerve assessment include advanced esthesiometers, quantitative sensory testing (QST), and functional magnetic resonance imaging (fMRI). The emerging technologies also include AI-driven analytical platforms that can be applied to both structural and functional methods. These various nerve assessment modalities can aid in delineating DED subtypes, selecting targeted treatments, monitoring nerve regeneration, and predicting treatment outcomes. By integrating structural and functional assessments, these technologies are reshaping the diagnosis, phenotyping, and management of DED and other related OSDs, paving the way for personalized therapeutic approaches. Full article

This study describes the clinical and genetic features of Meesmann epithelial corneal dystrophy (MECD) in two unrelated families and reports new genotype–phenotype associations. Ten patients from a Lebanese family (n = 4) (Family 1) and a Spanish family (n = 6) (Family 2) underwent ophthalmologic evaluation, in vivo confocal microscopy (IVCM), anterior segment optical coherence tomography (AS-OCT) with epithelial thickness mapping (ET-map), and targeted next-generation sequencing (NGS) using a custom-designed 133-gene panel associated with anterior segment dystrophies. In Family 1, a novel homozygous KRT12 c.1181T>C (p.Leu394Pro) variant was identified in the symptomatic proband and his clinically asymptomatic brother, while both parents, who were first cousins, were heterozygous for this nucleotide variant. The proband also carried the heterozygous KRT3 c.250C>T (p.Arg84Trp) variant, which has been previously reported but, to our knowledge, has not been described in co-occurrence until now. In addition, the proband showed a complex phenotype with signs of MECD and epithelial basal membrane alterations consistent with epithelial basement membrane dystrophy (EBMD). In Family 2, four affected members carried the KRT3 c.1492G>A (p.Glu498Lys) variant in heterozygosity, which has been previously described. The elderly members affected showed typical signs of MECD and EBMD. To our knowledge, these concomitant alterations have not been previously described with genetical confirmation. In conclusion, this study provides the first evidence that the co-occurrence of variants in two Meesmann corneal dystrophy-associated genes (KRT3 and KRT12) can jointly account for the disease phenotype. We also highlight the association of MECD with EBMD in both families. Characterization using IVCM and AS-OCT ET-Map provides a deeper understanding of the morphological changes and phenotypic variability in MECD, confirming the utility of this multimodal imaging approach for diagnosis and management. Full article

Background/Objectives: To develop and validate the DMEK Risk and Outcome Prediction (DROP) Score—a benchmarking model integrating patient, donor, surgical, and center-specific parameters for individualized risk assessment following DMEK. Methods: The DROP Score comprises four subscores, namely the Patient Risk Profile (PRP), Donor Tissue Quality (DTQ), Surgical Complexity Index (SCI), and Center Performance Factor (CPF), with literature-derived weights ($\alpha$ = 0.40, $\beta$ = 0.25, $\gamma$ = 0.20, $\delta$ = 0.15) validated by sensitivity analysis (K = 0.82–0.91). Clinical validation included 76 DMEK eyes and 89 controls (2019–2023). Machine learning models utilized EfficientNetV2B3 transfer learning with Random Forest classifiers and patient-level data partitioning. IVCM imaging comprised 6200 images. Results: The mean DROP Score was 39.35 ± 7.61 (Moderate: 92.1%; High: 7.9%). High-risk patients showed worse 12-month BCVA (0.50 vs. 0.31 logMAR) and higher poor prognosis rates (50.0% vs. 34.3%). The DROP Score showed significant correlations with BCVA (r = 0.305, p = 0.007) and ECD (r = −0.352, p = 0.002). Tissue classification accuracy reached 96.2%. Diabetes mellitus emerged as the strongest prognostic factor (OR: 4.34, p = 0.012), followed by hypertension (OR: 2.65, p = 0.078). Conclusions: The DROP Score provides transparent, individualized DMEK risk assessment. Diabetes mellitus and hypertension emerged as dominant systemic prognostic factors, while rebubbling showed no adverse impact on long-term outcomes. Complete four-domain validation requires ongoing prospective data collection. Full article

Dry eye disease (DED) is a multifactorial disorder of the ocular surface, characterised by tear film instability, hyperosmolarity, inflammation, and neurosensory abnormalities. Its clinical heterogeneity and the weak correlation between symptoms and signs complicate both diagnosis and management. Conventional assessments, such as patient-reported symptom questionnaires and basic clinical tests like the Schirmer test, are useful; however, their variability and limited sensitivity highlight the need for more reliable and objective diagnostic tools. This narrative review summarises and analyses current imaging approaches used for the diagnosis of DED. A comprehensive literature search was performed in the PubMed and Google Scholar databases to identify relevant studies published up to October 2025. In recent years, imaging technologies have revolutionised the approach to DED. Modalities such as in vivo confocal microscopy (IVCM), meibography, anterior segment optical coherence tomography (AS-OCT), interferometry, thermography, tear fluorescein clearance, impression cytology, and multifunctional imaging systems allow for non-invasive, high-resolution, and reproducible assessment of ocular surface structures and tear film dynamics. The integration of these techniques into clinical practice supports a more personalised management of DED. Future directions include further technological refinements and the application of artificial intelligence (AI) to imaging analysis, with the potential to enhance diagnostic precision and facilitate earlier intervention. While imaging cannot replace a thorough clinical examination, it has become an essential adjunct that significantly enriches the evaluation and management of patients with DED. Full article

Ocular surface lesions represent a diverse group of pathologies which may be challenging to diagnose clinically. Anterior segment imaging—including anterior segment optical coherence tomography (AS-OCT), optical coherence tomography angiography (OCTA), ultrasound biomicroscopy (UBM), and in vivo confocal microscopy (IVCM)—provides valuable adjunct information for the diagnosis, management, and monitoring of these lesions. The present review aims to provide an update on the principles, current clinical applications, advantages, limitations, and recent advancements in the imaging modalities used for the evaluation of ocular surface lesions. Notable recent advancements include the application of artificial intelligence in the interpretation of AS-OCT, intraoperative use of AS-OCT, the development of three-dimensional UBM, and expanded applications of each modality for a variety of ocular surface lesions. Full article

Background: Fungal keratitis remains a serious threat to vision, often progressing despite medical therapy and requiring surgical intervention. Therapeutic deep anterior lamellar keratoplasty (DALK) and therapeutic penetrating keratoplasty (TPK), are frequently required but carry risks of infection recurrence and graft rejection. As timely identification of the etiological agent is essential for improving the outcomes in infectious keratitis, in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) are instrumental in providing insights that can guide better therapeutic decision-making and improving outcomes in fungal keratitis. Case Description: We report the cases of two previously healthy patients (case one, 56-year-old woman; case two, 38-year-old man), who have presented in our service with unilateral infectious keratitis after ocular trauma with vegetable matter during outdoor activities, with a visual acuity of counting fingers and hand motion, respectively. Slit-lamp examination revealed unilateral extensive corneal infiltrates suggestive for fungal etiology in both cases. In vivo confocal microscopy (HRT-3, Heidelberg Retina Tomograph 3/Rostock Cornea Module, Heidelberg Engineering, Heidelberg, Germany) identified lesions suggestive for Candida Albicans and Acanthamoeba coinfection in case one and filamentous fungal keratitis in case two. Anterior segment optical coherence tomography (MS-39, CSO, Italy) was used to monitor the extent and morphology of the infiltrates. The patients underwent therapeutic DALK and TPK, respectively, with good results at the one-year follow-up. Conclusions: Our cases illustrate the advantages of incorporating IVCM and AS-OCT as complementary imaging techniques into clinical practice. IVCM and AS-OCT in fungal keratitis could lead to an earlier diagnosis, more accurate dynamic treatment response evaluation, and the identification of high-risk features for aggressive fungi for a more tailored medical and surgical management. Full article

Background: In vivo confocal microscopy (IVCM) provides high-resolution corneal imaging that may enhance preoperative and postoperative assessment in refractive surgery. This pilot study aimed to evaluate the diagnostic utility of IVCM in identifying subclinical corneal abnormalities that could influence surgical qualification and outcomes. Methods: A total of 7 patients (3 males, 4 females; mean age 48.8 ± 14.5 years) undergoing qualification or follow-up for refractive surgery were prospectively examined between May 2021 and March 2025. Each participant underwent a comprehensive ophthalmic evaluation, including slit-lamp biomicroscopy, corneal topography, anterior segment optical coherence tomography (AS-OCT), and IVCM using the Heidelberg Retina Tomograph II with Rostock Cornea Module. Patients with prior ocular surgery, active infection, or systemic corneal disease were excluded. Results: IVCM revealed subtle epithelial, stromal, and endothelial abnormalities undetectable by conventional methods. Findings such as Thygeson’s keratitis, pre-Descemet’s dystrophy, and subclinical herpes simplex keratitis led to modifications of surgical plans or disqualification in selected cases. The technique also aided postoperative evaluation of epithelial–stromal interface disorders. Conclusions: IVCM proved to be a valuable adjunct in detecting subclinical corneal pathology, refining patient selection, and improving safety in refractive surgery. Larger multicenter studies are warranted to validate its clinical role and define standardized indications for preoperative screening. Full article

Objectives: The aim of this study was to assess the accuracy of corneal in vivo confocal microscopy (IVCM) in the diagnostic process of small fibre neuropathy (SFN) compared to skin biopsy. Methods: This cross-sectional observational study was performed at the Eye Hospital and Institute of Neurophysiology, University Medical Centre Ljubljana, and included 35 patients with a clinical picture of SFN. All patients underwent a neurological exam that included an SFN questionnaire, standard skin biopsy, and ophthalmological assessment, including corneal IVCM. Results: Skin biopsy confirmed SFN in 14/35 patients (40%). These patients had a significantly shorter corneal nerve fibre length (CNFL) compared to those with negative biopsy (13.67 ± 2.99 mm/mm² vs. 16.27 ± 3.54 mm/mm², p = 0.030), as well as reduced corneal nerve branch density (CNBD) (36.68 ± 14.68 branches/mm² vs. 48.81 ± 17.83 branches/mm², p = 0.042). CNFL reduction below the 5th percentile was proven in 13/35 patients, yielding 64.3% sensitivity (95% CI: 35.1–87.2%) and 80.9% specificity (95% CI: 58.1–94.6%) compared to skin biopsy. In idiopathic SFN, negative IVCM results aligned with negative biopsies in 90% (95% CI: 55.5–99.8%) of cases. Meanwhile, in secondary SFN, positive IVCM results detected evidence of peripheral neurodegeneration in an additional 27.3% (95% CI: 6–61%) with negative skin biopsy. Conclusion: CNFL reduction in corneal IVCM demonstrated significant diagnostic value for SFN. Since skin biopsy findings do not always correspond with IVCM findings, corneal IVCM could be applied as a complementary tool to standard skin biopsy rather than as a replacement. It might be additionally useful for detecting patchy pattern presentations of SFN, excluding neuropathy in idiopathic SFN, and detecting neuropathy in biopsy-negative secondary SFN. In patients with positive IVCM, it could also be used as a primary tool for follow-up monitoring. Full article