Search Results (48)

Background/Objectives: Dry eye disease (DED) is a multifactorial condition with complex pathophysiology involving tear film instability, ocular surface inflammation, and nerve dysfunction. This review summarizes current evidence on the different available therapies targeting these mechanisms. Methods: A review of clinical studies evaluating treatment outcomes for therapies targeting aqueous tear deficiency, Meibomian gland dysfunction, ocular surface inflammation, and ocular pain was conducted, with an emphasis on randomized controlled trials and meta-analyses where available. Results: Artificial tears provide symptomatic relief with limited impact on tear film stability. Punctal plugs improve tear retention but show variable efficacy across studies. Treatments targeting MGD—such as lipid-based lubricants, eyelid hygiene, thermal pulsation (LipiFlow, iLux), and intense pulsed light (IPL)—demonstrate improvements in gland function, though outcomes vary. Anti-inflammatory agents including cyclosporine, lifitegrast, and short-term corticosteroids improve ocular surface signs, with mixed symptom relief. Biologic therapies like autologous serum tears and platelet-rich plasma show promise for both signs and symptoms, but data remain inconsistent. Nerve-targeted therapies, including oral neuromodulators (gabapentin, antidepressants), botulinum toxin, and transcutaneous nerve stimulation, have shown potential for managing neuropathic ocular pain, although randomized data are limited. Overall, variability in study designs, patient populations, and outcome measures highlights the need for more rigorous research. Conclusions: Personalized, mechanism-based treatment strategies are essential for optimizing outcomes in DED. Future research should prioritize well-designed, controlled studies to clarify the role of emerging therapies and guide the individualized management of this heterogeneous condition. Full article

Background: Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, and frequently severe allergic ocular condition predominantly impacting children and adolescents in tropical and subtropical areas. It profoundly affects patients’ quality of life owing to its chronic symptoms and possible vision-threatening effects. Notwithstanding progress in comprehending VKC, its ocular symptoms and therapeutic approaches necessitate ongoing assessment. Aims: This review summarizes the main factors to consider when diagnosing, treating, and managing patients with VKC based on the current literature in this field. Methods: This comprehensive review examined peer-reviewed literature from 2010 to 2024 obtained from PubMed. The selection criteria encompassed research addressing the clinical presentation, diagnostic difficulties, and therapy of visual symptoms in pediatric patients with VKC. The publications chosen were those focusing on those that elucidate the pathophysiology, consequences, and innovations in treatment methodologies. Results: The ocular manifestations of VKC are varied and characterized by prominent symptoms such as severe itching, photophobia, lacrimation, and a viscous mucoid discharge. Clinical manifestations range from conjunctival hyperemia and limbal thickening to severe consequences that jeopardize vision, including shield ulcers and keratoconus. Improvements in imaging techniques such as anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy have enhanced diagnostic accuracy. The pharmacological approach has transitioned to steroid-sparing techniques, prioritizing mast cell stabilizers, antihistamines, and immunomodulators such as cyclosporine. Novel therapies, including biologics that target interleukin pathways, demonstrate potential in refractory instances. Nonetheless, access to modern medicines is restricted in resource-limited environments. Conclusions: VKC poses considerable diagnostic and treatment difficulties due to its chronic nature and possible consequences. This review emphasizes the necessity for prompt diagnosis and customized management approaches to avert vision impairment. Despite considerable advancements in comprehending VKC’s etiology and therapy, inequalities in access to sophisticated care highlight the necessity for global activities to guarantee equitable treatment alternatives. Full article

Objectives: We aimed to investigate dry eye parameters as potential predisposing factors and estimate the prevalence of high-frequency topical eye drop usage. Methods: A total of 5594 dry eye patients treated between November 2015 and June 2022 were included. High users (n = 180) were those who applied at least one artificial tear drop per hour, whereas those who used artificial tears fewer than four times daily were classified as low users (n = 5414). Differences in self-reported symptoms (OSDI, SPEED questionnaires) and tear-related parameters, including severity of corneal staining (SPK), fluorescein tear-film break-up time (FTBUT), lipid layer thickness (LLT), number of expressible meibomian glands (MGE), meiboscale, and blink patterns, were assessed. Subsequent follow-up comprehensive dry eye assessments were performed at 3 months. Results: There was no difference in age or sex between high users and low users (p = 0.075 and 0.508, respectively). High users had significantly higher symptom scores (p < 0.001), more total blinks (p = 0.001), lower Schirmer scores (p < 0.001), higher SPK grades (p < 0.001), shorter FTBUT (p = 0.010), and higher limbal redness scores (p = 0.002). However, there were no differences in the LLT, MGE, or meiboscale. The compliance with follow-up examinations at 3 months was significantly greater for the high users (p < 0.001). Patients with OSDI scores > 40, SPEED scores > 12, Schirmer scores ≤ 3 mm, and higher compliance with follow-up examinations had odds ratios of 4.0, 3.3, 1.7, and 4.1, respectively, for being high users (95% confidence intervals = 2.8–5.8, 2.4–4.7, 1.2–2.3 and 2.7–5.2, respectively). Among the high users, reducing topical drops significantly decreased the SPEED and OSDI scores, except for the environmental trigger factor in the OSDI questionnaire. During long-term follow-up, 1.1% of low users and 15.4% of high users received cyclosporine treatment (odds ratio 16.4, p < 0.001). Conclusions: OSDI scores > 40, SPEED scores > 12, and Schirmer scores ≤ 3 mm were associated with high-frequency eye drop usage, which accounted for 3.2% of moderate to severe dry eye patients. Susceptibility to environmental triggers could represent hyperalgesia/allodynia in high users. High users have a higher need for cyclosporine treatment. Full article

Background/Objectives: We aimed to evaluate the effectiveness of a 0.1% cyclosporin A cationic emulsion (CsA-CE) for dry eye disease (DED) post-cataract surgery using the DED index measured with a Placido tear film analyzer. Methods: We retrospectively reviewed the medical records of patients who underwent simple cataract surgery. All patients used 0.5% moxifloxacin and 1% prednisolone acetate eye drops four times daily postoperatively. They were divided into the CsA-CE and control groups based on whether they had used CsA-CE 1 week after surgery. Subjective and objective assessments were performed at the baseline and 1 month postoperation. The non-invasive tear meniscus height, non-invasive tear break-up time, conjunctival redness, meibomian gland morphology, and lipid layer thickness were assessed using the Keratograph 5M (Oculus). Results: No differences were observed in the preoperative dry eye parameters between the groups. The ocular surface disease index decreased from 19.26 to 14.58 (p = 0.046) at 1 month postoperation for the CsA-CE group, and the average non-invasive tear break-up time significantly increased from 10.97 to 13.00 s (p = 0.002). No such differences were observed for the control group. Nasal bulbar conjunctival hyperemia increased (p < 0.001) for the control group. Nasal limbal hyperemia and overall limbal hyperemia increased for both groups (CsA-CE, p = 0.005, 0.017; control, p = 0.001, 0.012). The lipid layer thickness increased from 70.29 to 86.41 nm for the CsA-CE group (p < 0.001), whereas no significant change was noted for the control group. Conclusions: CsA-CE (0.1%) is effective for treating DED after cataract surgery and improves the tear lipid layer. Full article

Background: The aim of the present study was to establish a cut-off value of the Lipid Layer Pattern (LLP) between participants with different subtypes of Dry Eye Disease (DED) including Deficient Dry Eye (ADDE), Evaporative Dry Eye (EDE), and Mixed Dry Eye (MDE). Methods: 240 participants diagnosed with DED according to the Tear Film and Ocular Surface Society in the Dry Eye Workshop II guidelines were included in the study. Tear Meniscus Height (TMH) using the Tearscope illumination and Meibomian Gland Loss Area (MGLA) using the Keratograph 5M were assessed to categorize the participants into an ADDE group, EDE group, or MDE group. Then, the LLP was assessed using the Tearscope following the Guillon (LLP-G) and Colour (LLP-C) schemes. Results: Receiver Operating Characteristics (ROC) showed that both LLP-G and LLP-C have no diagnostic potential in distinguishing between ADDE and EDE participants (both p ≥ 0.724). However, to differentiate the ADDE participants from the MDE, ROC procedures showed a good diagnostic potential with cut-off values of Closed Meshwork-Wave (AUC ± SD = 0.609 ± 0.049, p = 0.038, sensitivity: 23.9%; specificity: 76.1%) and Grey-White (AUC ± SD = 0.611 ± 0.050, p = 0.034, sensitivity: 40.7%; specificity: 73.9%) for LLP-G and LLP-C, respectively. Also, a significant potential to distinguish between the EDE from MDE participants was found, with cut-off values of Closed Meshwork (AUC ± SD = 0.604 ± 0.049, p = 0.043, sensitivity: 40.8%; specificity: 76.1%) and Grey-White (AUC ± SD = 0.604 ± 0.051, p = 0.038, sensitivity: 44.7%; specificity: 73.9%) for LLP-G and LLP-C, respectively. Conclusions: Using the Tearscope, both LLP-G and LLP-C has diagnostic potential to distinguish MDE participants from the other subtypes of DED. Full article

Background: Metformin, a commonly prescribed medication for managing diabetes, has garnered increasing interest as a potential therapeutic option for combating cancer and aging. Methods: The current study investigated the effects of metformin treatment on human meibomian gland epithelial cells (hMGECs) at morphological, molecular, and electron microscopy levels. HMGECs were stimulated in vitro with 1 mM, 5 mM, and 10 mM metformin for 24, 48, and 72 h. The assessed outcomes were cell proliferation assays, lipid production, ultrastructural changes, levels of IGF-1, Nrf2, HO-1, apoptosis-inducing factor 1 (AIF1) at the protein level, and the expression of oxidative stress factors (matrix metallopeptidase 9, activating transcription factor 3, CYBB, or NADPH oxidase 2, xanthine dehydrogenase). Results: Morphological studies showed increased lipid production, the differentiation of hMGECs after stimulation with metformin, and the differentiation effects of undifferentiated hMGECs. Proliferation tests showed a reduction in cell proliferation with increasing concentrations over time. AIF1 apoptosis levels were not significantly regulated, but morphologically, the dying cells at a higher concentration of 5-10 mM showed a rupture and permeabilization of the plasma membrane, a swelling of the cytoplasm, and vacuolization after more than 48 h. The IGF-1 ELISA showed an irregular expression, which mostly decreased over time. Only at 72 h and 10 mM did we have a significant increase. Mitochondrial metabolic markers such as Nrf2 significantly increased over time, while HO-1 decreased partially. The RT-PCR showed a significant increase in MMP9, CYBB, XDH, and ATF with increasing time and metformin concentrations, indicating cell stress. Conclusions: Our results using a cell line suggest that metformin affects the cellular physiology of meibomian gland epithelial cells and induces cell stress in a dose- and duration-dependent manner, causing changes in their morphology and ultrastructure. Full article

Dry eye disease (DED) has become increasingly prevalent in the digital era, largely due to prolonged screen exposure. The excessive use of digital devices contributes to inappropriate blink frequency and dynamics, leading to ocular surface dryness and discomfort. Additionally, digital screen use has broader implications for systemic health, including visual strain, headaches, and disrupted circadian rhythms caused by blue light exposure. Previous studies have shown that prolonged screen time correlates with altered blink frequency and increased symptom severity in DED patients, exacerbating the imbalance in tear film production and evaporation. Blinking dynamics, particularly blink rate and completeness, are crucial in maintaining ocular surface moisture. Incomplete blinking impairs meibomian gland function, reducing lipid secretion, which is essential for preventing tear evaporation. Raising patient awareness through educational material, ergonomic adjustments, and blinking exercises has been shown to mitigate these effects. Digital tools that provide targeted educational interventions can be particularly effective in improving blink dynamics and overall ocular comfort. This study evaluates the efficacy of digital applications in optimizing blinking dynamics and enhancing tear film stability. The findings suggest that these innovations improve patient outcomes by encouraging healthier eye care practices. However, further research is needed to assess their long-term impact across diverse populations. Full article

Background: To determine the differences in the effects of intense pulsed light (IPL) treatment when including the upper and lower lid or lateral canthus area in patients with meibomian gland dysfunction (MGD). Methods: Patients who underwent three IPL treatment sessions at 3-week intervals were divided into three groups according to the treatment sites: group A, lower lid; group B, upper and lower lids; and group C, lower lid and lateral canthal area. Before and after the IPL treatment sessions, we obtained the lid abnormality score (LAS), meibum expressibility (ME), meibum quality (MQ), lipid layer thickness (LLT), type I Schirmer test (ST), tear break-up time (TBUT) test, corneal fluorescein staining scores (CFSs), and Ocular Surface Disease Index (OSDI). Results: IPL treatment significantly improved LASs, ME, MQ, TBUT, CFS, and OSDI values in all groups. Differences in LAS values before and after IPL treatment were significantly greater in groups B and C than those in group A. Conclusions: IPL treatment encompassing the upper lid and lateral canthus together with the lower lid elicited additional improvement in patients with MGD. The additional effect on treating the lateral canthus was similar to the effect observed on the additional treatment of the upper lid. Full article

Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in meibum composition lead to different ocular alterations like Meibomian Gland Dysfunction (MGD) and subsequent Evaporative Dry Eye (EDE). The aim of the present study was to investigate the composition and abundance of meibum lipids and their relationship with eyelid margin abnormalities, lipid layer patterns and MG status. The study utilizes a lipidomic approach to identify and quantify lipids in meibum samples using an Elute UHPLC system. This system considered all four dimensions (mass/charge, retention time, ion mobility and intensity) to provide the accurate identification of lipid species. Samples were categorized as healthy or low/no signs of alteration (group 1) or severe signs of alteration or EDE/MGD (group 2). The current investigation found differences in Variable Importance in Projection lipid abundance between both groups for the MGD signs studied. Changes in meibum composition occur and are related to higher scores in eyelid margin hyperaemia, eyelid margin irregularity, MG orifice plugging, MG loss and lipid layer pattern. Full article

Ophthalmic nanoemulsions that can treat the deficiencies of meibum (MGS) in Meibomian gland disease and restore its functionality in the tear film are greatly sought. The Rohto Dry Aid (RDA) formulation employs TEARSHIELD TECHNOLOGY^TM, which uses a multicomponent oil phase of polar and non-polar lipid-like molecules selected to mimic the profiles of healthy meibum. Thus, the interactions of RDA with “diseased” Meibomian (dMGS) films merit deeper analysis, as these interactions might offer important clues for both the development of new ocular formulations and the processes behind the therapeutic action of the nanoemulsions. Pseudobinary dMGS/RDA films were spread at the air–water surface of the Langmuir trough. Surface pressure-area isocycles and stress relaxations were used to access the layer’s response to blink-like cycling and dilatational viscoelasticity, respectively, while film morphology was recorded via Brewster angle microscopy. It was found that RDA is able to reverse the brittleness and to restore the stability of “diseased” MGS films and thus to revert the layer’s properties to the functionality of healthy Meibomian lipids. Therefore, in order to effectively treat dry eyes with MGS-oriented therapy, ophthalmic nanoemulsions warrant more research. Full article

While the involvement of thermosensitive transient receptor potential channels (TRPs) in dry eye disease (DED) has been known for years, their expression in the meibomian gland (MG) has never been investigated. This study aims to show their expression and involvement in the lipogenesis of the MG, providing a possible new drug target in the treatment of DED. Our RT-PCR, Western blot and immunofluorescence analysis showed the expression of TRPV1, TRPV3, TRPV4 and TRPM8 in the MG at the gene and the protein level. RT-PCR also showed gene expression of TRPV2 but not TRPA1. Calcium imaging and planar patch-clamping performed on an immortalized human meibomian gland epithelial cell line (hMGECs) demonstrated increasing whole-cell currents after the application of capsaicin (TRPV1) or icilin (TRPM8). Decreasing whole-cell currents could be registered after the application of AMG9810 (TRPV1) or AMTB (TRPM8). Oil red O staining on hMGECs showed an increase in lipid expression after TRPV1 activation and a decrease after TRPM8 activation. We conclude that thermo-TRPs are expressed at the gene and the protein level in MGs. Moreover, TRPV1 and TRPM8’s functional expression and their contribution to their lipid expression could be demonstrated. Therefore, TRPs are potential drug targets and their clinical relevance in the therapy of meibomian gland dysfunction requires further investigation. Full article

Meibomian gland dysfunction (MGD) is one of the main causes of dry eye disease. To better understand the physiological functions of human meibomian glands (MGs), the present study compared MGs with free sebaceous glands (SGs) and hair-associated SGs of humans using morphological, immunohistochemical, and liquid chromatography—mass spectrometry (LCMS)-based lipidomic approaches. Eyelids with MGs, nostrils, lips, and external auditory canals with free SGs, and scalp with hair-associated SGs of body donors were probed with antibodies against cytokeratins (CK) 1, 8, 10, and 14, stem cell markers keratin 15 and N-cadherin, cell–cell contact markers desmoglein 1 (Dsg1), desmocollin 3 (Dsc3), desmoplakin (Dp), plakoglobin (Pg), and E-cadherin, and the tight junction protein claudin 5. In addition, Oil Red O staining (ORO) was performed in cryosections. Secretions of MGs as well as of SGs of nostrils, external auditory canals, and scalps were collected from healthy volunteers, analyzed by LCMS, and the data were processed using various multivariate statistical analysis approaches. Serial sections of MGs, free SGs, and hair-associated SGs were 3D reconstructed and compared. CK1 was expressed differently in hair-associated SGs than in MGs and other free SGs. The expression levels of CK8, CK10, and CK14 in MGs were different from those in hair-associated SGs and other free SGs. KRT15 was expressed differently in hair-associated SGs, whereas N-cadherin was expressed equally in all types of glands. The cell–cell contact markers Dsg1, Dp, Dsc3, Pg, and E-cadherin revealed no differences. ORO staining showed that lipids in MGs were more highly dispersed and had larger lipid droplets than lipids in other free SGs. Hair-associated SGs had a smaller number of lipid droplets. LCMS revealed that the lipid composition of meibum was distinctively different from that of the sebum of the nostrils, external auditory canals, and scalp. The 3D reconstructions of the different glands revealed different morphologies of the SGs compared with MGs which are by far the largest type of glands. In humans, MGs differ in their morphology and secretory composition and show major differences from free and hair-associated SGs. The composition of meibum differs significantly from that of sebum from free SGs and from hair-associated SGs. Therefore, the MG can be considered as a highly specialized type of holocrine gland that exhibits all the histological characteristics of SGs, but is significantly different from them in terms of morphology and lipid composition. Full article

The main function of exocrine Meibomian glands (MGs) is to produce a lipid-rich secretion called meibum which plays a critical role in maintaining the ocular surface homeostasis of humans and most mammals. The chemical composition of meibum, and its quantity produced by MGs, largely determine whether it can fulfill its role successfully. Aging was frequently associated with the onset of various MG-related pathologies. The goal of this study was to determine how aging affects the chemical composition and quantity of meibum in mice, and identify possible molecular markers of aging. Unbiased, untargeted and targeted lipidomic evaluation of mouse MG lipids was conducted using liquid chromatography—high-resolution mass spectrometry, and the results were analyzed using Principal Component, Orthogonal Projections to Latent Structures Discriminant, and Partial Least Square Discriminant Analyses. We found that aging leads to dysregulation of lipid metabolism in MGs, changing the ratios of major classes of MG lipids (such as wax esters, triacylglycerols, and phospholipids) in a progressive manner. Several lipid species that belong to these groups of MG lipids are proposed as clear markers of aging in a mouse model. Full article

Posterior blepharitis and dry eye are common disorders with meibomian gland dysfunction (MGD), a principal driver of their pathophysiology. Meibomian gland dysfunction is increasingly prevalent in older populations with contributory hormonal imbalances. The abnormal meibum in MGD has been documented to have an excess of cholesterol with a resultant disruption of the lipid layer of the tear film. This leads to tear film instability due to the inadequate trapping of the aqueous portion of the tear film with resultant evaporative dry eye. Significant morbidity may follow MGD with ocular surface inflammation disrupting both social and work function. Rosacea is a common chronic inflammatory condition of the central face but can have ocular and systemic inflammatory associations. It is especially prevalent in North European populations and can have onset at any age, but commonly presents between thirty and fifty years of age. In ocular rosacea, MGD is a recognised manifestation as is dyslipidaemia. Ocular rosacea can predate cutaneous disease. As yet, there is no directly reported evidence of the efficacy of the early identification and treatment of ocular rosacea with associated dyslipidaemia and systemic inflammation. We posit that MGD in ocular rosacea sufferers may be a marker for dysregulated cholesterol synthesis and inflammation, and that statins maybe a potential therapy. This article introduces potential strategies to utilise ocular rosacea MGD as a possible marker for ophthalmologists, cardiologists, and primary healthcare physicians to treat rosacea-associated dyslipidaemia and systemic inflammation. This could aid in overall cardiovascular morbidity and mortality control for rosacea sufferers, potentially at an earlier age, while also addressing their tear film de-stabilisation through cholesterol lowering and inflammation reduction. Full article

Purpose: This study aims to compare dry eye parameters before and after COVID-19 infection in dry eye patients. Methods: We included 44 dry eye patients (88 eyes) from our existing dry eye cohort, with 22 belonging to the post-COVID-19 group due to a prior COVID-19 infection and the other 22 forming the non-COVID-19 group as they had no history of COVID-19. We examined and compared the dry eye parameters of the post-COVID-19 group, including the ocular surface disease index (OSDI), Schirmer’s test results (ST), non-invasive Keratography tear break-up time (NIKBUT), lipid layer thickness (LLT), Meibomian gland dysfunction (MGD), and the grading of papillae and follicles, both before and after the COVID-19 infection. We also compared the dry eye parameters difference of the post-COVID-19 group with the non-COVID-19 group. Results: The post-COVID-19 group was comprised of individuals with an average age of 38.36 ± 14.99 years, of which 82% were female. The time interval between the two tests was 16.92 ± 5.40 months, which did not differ significantly from the non-COVID-19 group. Compared to the pre-COVID-19 eyes, the post-COVID-19 eyes showed a significant decrease in the average LLT (52.86 ± 18.00 nm vs. 63.00 ± 22.40 nm, p < 0.001), as well as the maximum LLT (67.89 ± 20.81 nm vs. 78.48 ± 20.55 nm, p < 0.001). The MGD in both the upper (1.75 ± 0.84) and lower eyelids (1.43 ± 0.73) worsened after a COVID-19 infection. Additionally, the grading of papillae was worse following a COVID-19 infection (0.61 ± 0.69 vs. 0.16 ± 0.37, p < 0.001). The multivariate linear regression model revealed a negative association between COVID-19 infection and NIKBUT-average (β = −2.98, 95%CI: (−5.82, −0.15), p = 0.039), LLT-average (β = −14.12, 95%CI: (−22.66, −5.59), p = 0.001), and LLT max (β = −15.65, 95%CI: (−23.09, −8.20), p < 0.001). Conclusion: From preliminary results, we concluded that dry eye patients who have been infected with COVID-19 appear to have a more severe dry eye condition, as evidenced by lower LLT, worse papillae and MGD, and shorter NIKBUT. It is important to raise awareness of this potential long-term symptom of COVID-19, especially among existing dry eye patients. Full article