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Introduction: Dry eye disease (DED) is a multifactorial condition of the ocular surface (OS) characterized by loss of tear film homeostasis, ocular discomfort, and vision disturbances. Most available ocular lubricants target the aqueous deficiency of the tear, restoring only this layer, leaving the tear lipid stratum deficient, as occurs in most patients with evaporative DED. An innovative propylene glycol-hydroxypropyl guar enriched with a phospholipid nanoemulsion (PG-HPG-PH-N) is indicated to restore deficiencies in both the lipid and aqueous layers of the tear film, and its composition was designed to increase lubricant retention on the OS. The purpose of this study was to evaluate, through the Ocular Surface Disease Index (OSDI) and clinical assessment, the treatment of patients who had DED due to aqueous deficiency arising from mixed or evaporative DED subtypes with a PG-HPG-PH-N ocular lubricant at a reduced frequency of twice a day, in a prospective, multicenter, and single-arm study. Methods: Patients were screened from days − 7 to 0, and from day 1 (baseline and first day of treatment) to day 28 of treatment with this lubricant. After visit 1 (screening visit, days − 7 to 0), designed as pre-treatment OS assessment, patients returned to their research center on days 14 and 28 of treatment for a complete assessment, including anamnesis, the OSDI, corrected visual acuity, tear breakup time (TFBUT), OS staining evaluation, tolerability index, and environmental exposure questionnaire. Results: Seventy patients were enrolled in this study (60 women, 10 men), with a mean age of 45 (range 27–64) years. TFBUT results showed an improvement in tear film stability as vital dyes sodium fluorescein and lysamine green showed a decrease in corneal staining after 14 and 28 days of treatment. No significant adverse events were reported, demonstrating the good tolerability of the lubricant. Conclusions: The PG-HPG-PH-N nanoemulsion can be considered to be a safe and effective ocular lubricant for treating DED due to aqueous deficiency, both mixed and evaporative subtypes. Trial Registration: Brazilian National Research Ethics Commission (ReBEC registration number 16055). [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease (DED) is a frequently observed condition characterized by ocular discomfort and visual disturbance. It is highly prevalent and impairs patients' quality of life (QoL). This study assessed the benefit of a preservative-free bioprotectant eye drop formulation containing sodium hyaluronate and trehalose (SH-trehalose) with regards to DED, as well as patient satisfaction, through a large-scale real-life survey. Methods: In a multi-center, international, prospective observational study, subjects with DED received SH-trehalose for 84 days. Ocular Surface Disease Index (OSDI), Dry Eye Questionnaire-5 items (DEQ-5), and patient satisfaction were assessed at baseline, day 28, and day 84, and clinical evaluations included ocular surface staining, Schirmer test, tear film break-up time (TBUT), and conjunctival hyperemia at baseline and day 84. Results: A total of 312 patients were evaluated, of whom 82.4% were women. The mean age was 57.9 ± 15.2 years. The mean OSDI score at baseline was 41.7 ± 20.6. After 84 days, the mean OSDI score was 27.3 ± 19.8 (p < 0.001). The percentage of patients with a severe OSDI score decreased from 60.3 to 34.5%. The DEQ-5 score significantly (p < 0.001) improved after 28 and 84 days, as did patient satisfaction. Ocular surface staining, Schirmer test, TBUT, and conjunctival hyperemia scores improved significantly (all p < 0.001) for both eyes with SH-trehalose between baseline and day 84. Tolerance of SH-trehalose was good. Conclusions: SH-trehalose significantly improved the clinical signs and symptoms of DED after 84 days. Moreover, it significantly increased patient satisfaction and was well tolerated. Trial Registration: NCT04803240. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a leading cause of heart failure, disability and mortality worldwide. In this study, the effects of intramyocardial injection of human platelet lysate (HPL), bone marrow mesenchymal stem cells pretreated with HPL (PMSCs), and PMSC lysate (lys), alone and in combination were investigated on MI-induced by LAD ligation in male Wistar rats. The experiment was carried out on sham, vehicle (Veh), HPL, PMSCs, PMSC lysate (PMSC lys), HPL + PMSCs, and HPL + PMSC lys groups. SBP, DBP, and ± dp/dt max were monitored by the PowerLab physiograph. The MSC characteristics and CD31, NKX2.5, and cardiac troponin I (cTnI) contents were determined by flow cytometry, immunohistochemistry, and immunofluorescence, respectively. SBP, DBP, and ± dp/dt max that decreased in the MI group were recovered by HPL, PMSC, PMSC lys, HPL + PMSC, and HPL + PMSC lys treatments. CD31 density was higher in all treated groups compared to the Veh group. CD31 density in the HPL + PMSCs and HPL + PMSC lys groups was higher than in the PMSCs group. The number of Dil+/NKX2.5 + and Dil+/cTnI + cells was higher in the HPL + PMSCs group compared to the PMSCs group. The HPL and PMSCs mitigates heart injuries and cardiac dysfunction after MI. HPL provides an appropriate environment for cardiomyocyte differentiation from PMSCs. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a leading cause of heart failure, disability and mortality worldwide. In this study, the effects of intramyocardial injection of human platelet lysate (HPL), bone marrow mesenchymal stem cells pretreated with HPL (PMSCs), and PMSC lysate (lys), alone and in combination were investigated on MI-induced by LAD ligation in male Wistar rats. The experiment was carried out on sham, vehicle (Veh), HPL, PMSCs, PMSC lysate (PMSC lys), HPL + PMSCs, and HPL + PMSC lys groups. SBP, DBP, and ± dp/dt max were monitored by the PowerLab physiograph. The MSC characteristics and CD31, NKX2.5, and cardiac troponin I (cTnI) contents were determined by flow cytometry, immunohistochemistry, and immunofluorescence, respectively. SBP, DBP, and ± dp/dt max that decreased in the MI group were recovered by HPL, PMSC, PMSC lys, HPL + PMSC, and HPL + PMSC lys treatments. CD31 density was higher in all treated groups compared to the Veh group. CD31 density in the HPL + PMSCs and HPL + PMSC lys groups was higher than in the PMSCs group. The number of Dil+/NKX2.5 + and Dil+/cTnI + cells was higher in the HPL + PMSCs group compared to the PMSCs group. The HPL and PMSCs mitigates heart injuries and cardiac dysfunction after MI. HPL provides an appropriate environment for cardiomyocyte differentiation from PMSCs. [ABSTRACT FROM AUTHOR]

Evaporation profiles have a strong effect on tear film thinning and breakup (TBU), a key factor in dry eye disease (DED). In experiments, TBU is typically seen to occur in patterns that locally can be circular (spot), linear (streak), or intermediate to those states. We investigate a two-dimensional (2D) model of localized TBU using a Fourier spectral collocation method to observe how the evaporation distribution affects the resulting dynamics of tear film thickness and osmolarity, among other variables. We find that the dynamics are not simply an addition of individual 1D solutions of independent TBU events, and we show how the TBU quantities of interest vary continuously between spots and streaks in the shape of the evaporation distribution. We also find a significant speedup by using a proper orthogonal decomposition to reduce the dimension of the numerical system. The speedup will be especially useful for future applications of the model to inverse problems, allowing the clinical observation at scale of quantities that are thought to be important to DED but not directly measurable in vivo within TBU locales. [ABSTRACT FROM AUTHOR]

Introduction: Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM). Methods: The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project's webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis. Results: A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED. Conclusion: This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance. [ABSTRACT FROM AUTHOR]

Introduction: High-tech devices for the assessment of dry eye disease (DED) are increasingly available. However, the agreement between high- and low-tech parameters has been poorly explored to date. Trying to fill these gaps, we conducted a post hoc analysis on a recently published retrospective study on patients with DED receiving both low- and high-tech (Keratograph®) assessments, and treatment with different lubricating eyedrops. Methods: Six clinical questions were defined by the authors, considering literature gaps and their clinical experience, namely: (1) are NIKBUT-i and T-BUT interchangeable parameters? (2) What was the correlation between low- and high-tech parameters in untreated and treated patients with DED? (3) What was the correlation between signs and symptoms at baseline and during/after treatment? (4) Which parameters were better associated with symptoms? And with symptoms change over time? (5) What was the performance of NIKBUT-i and T-BUT in detecting clinically relevant changes? (6) What was the clinical advantage of adding other high- and low-tech parameters, respectively, to NIKBUT-i and T-BUT? Results: Low-tech measures were the best descriptors of the Ocular Surface Disease Index (OSDI) at baseline. In contrast, high-tech assessments demonstrate better performance in detecting changes over time. The distribution of NIKBUT-i data was more dispersed than TBUT both at baseline and follow-up. At a fixed specificity of 80%, the sensitivity in detecting clinically relevant ameliorations of symptoms was 42% for NIKBUT-i and 25% for T-BUT. A battery of high-tech tests could detect 90% of clinical amelioration, compared with 45% with low-tech tests (p < 0.001). Correlation between low- and high-tech parameters in both treated and untreated patients is lacking. Conclusions: Low-tech measures are adequate for diagnostic purposes in DED, whereas high-tech showed better performances at follow-up, particularly when different tests are combined. Overall, poor interchangeability among parameters and agreement with symptoms was reported both with high- and low-tech assessments. [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease (DED) is one of the most prevalent eye conditions worldwide, with artificial tears serving as a primary treatment option. Despite their wide availability on the European market, there is a lack of established classifications based on their physicochemical properties. The aim of our study was therefore (i) to develop an analytical method that measures the concentration and the molecular weight (MW) of the hyaluronic acid (HA) in commercialized products, and (ii) to propose an overview based on their various physicochemical parameters. Methods: The intrinsic viscosity and MW of the HA, as well as osmolarity, pH, rheological profile, and viscosity, were measured or determined. A specific method was developed to measure the average intrinsic viscosity and HA content using a liquid size-exclusion chromatography system. The MW was determined using the Mark–Houwink equation. Results: Thirty-seven products commercialized in Europe were analyzed, with 21 of them containing HA. The HA MW was lowest (300 kDa) for Thealose®, Thealoz Duo® Gel, and Hyabak®, and highest (1300 kDa) for Vismed® Multi, Vismed® Gel, and Neovis® Gel. The pH values varied between 5.94 for Treovis® and 8.06 for Systane® Ultra. Osmolarity ranged between 148 mOsm/L and 325 mOsm/L for Neovis® and Treovis®, respectively. Viscosity was highly variable, ranging from 0.38 mPas·s for Hylolipid® to 337.47 mPas·s for Thealoz® Duo Gel. Finally, rheological profile analysis revealed different shear-thinning behaviors. Conclusion: While the perfect eye drop does not exist, a multitude of options are available to choose from. This study improves our understanding of the major tear substitutes available on the European market based on several physicochemical properties. A better understanding and awareness of these parameters is crucial in order to offer the best treatment for patients with DED. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study is to assess the real-life efficacy and tolerance of a new preservative-free, surfactant-free latanoprost (PFSF-LAT) formulation. Methods: Retrospective, multicentre, non-comparative, observational study in patients with ocular hypertension or open angle glaucoma, naïve or non-naïve to previous intraocular pressure (IOP)-lowering treatment, and treated for at least 3 months with the study eye drop. IOP for worse eye, ocular signs and symptoms, and concomitant use of artificial tears were collected at study drug initiation and at last visit under treatment. Reasons for discontinuing the study eye drop (if relevant) and investigators' satisfaction were also assessed. Results: In the per protocol population (103 eyes; 63 naïve, 39 switched, 1 not classified because of missing data), IOP decreased significantly (p < 0.001) from 21.6 ± 5.0 mmHg at baseline to 16.1 ± 3.5 mmHg at the end of the study (mean reduction of − 5.5 ± 4.6 mmHg; − 25.5%). IOP in naïve patients was significantly improved, with a mean reduction of 7.1 mmHg (− 30.7%), which was within expected latanoprost IOP-lowering effect. Interestingly, in previously treated patients, switching to PFSF-LAT also allowed for a further 2.9 mmHg decrease in IOP (p < 0.001). The incidence of ocular side effects at study initiation was significantly (p < 0.001) reduced from 31.1% to 11.3% in the overall population, and from 65.0% to 7.5% in switched patients. This included conjunctival hyperaemia and superficial punctate keratitis (from 42.5% to 2.5% and from 37.5% to 2.5% in switched patients, respectively). According to investigators, tolerance and efficacy of the study eye drop were satisfactory or very satisfactory in 98.1% and 83.2% of patients, respectively. Conclusion: PFSF-LAT is an efficient treatment for patients with glaucoma with an improved tolerance profile. It can be considered as initial therapy in naïve patients or in patients with poor ocular tolerance to previous IOP-lowering eye drops. [ABSTRACT FROM AUTHOR]

Introduction: Patients with dry eye disease (DED) complain of a multitude of symptoms that affect their visual function and quality of life (QoL). This clinical investigation assessed the performance, tolerance, and safety of a novel preservative-free ophthalmic solution containing xanthan gum 0.2% and desonide sodium phosphate 0.025%. Methods: This was an observational, prospective, multicentric, and post-market clinical investigation to assess the effect of three times a day instillation of the study formulation in patients suffering from DED. The primary objective was to achieve a 50% reduction in conjunctival hyperemia index as assessed with the OCULUS Keratograph after 1 month of treatment compared to baseline values. The secondary objectives included patient-reported outcomes, clinical performance, and safety. Results: Thirty patients were enrolled (21 women, 9 men) with a mean age of 61.10 ± 14.53 years. The instillation of the study formulation was associated with a significant reduction in redness scores after 1 month of treatment compared to baseline (mean − 0.51 ± 0.51; p ≤ 0.0001). Although the primary endpoint was not completely met, a 50% reduction in the conjunctival hyperemia index was achieved in 23% of the participants, and 77% showed a reduction of 26% of the same index. In addition, the ophthalmic solution significantly increased tear film break-up time, and a significant reduction of corneal and conjunctival staining with fluorescein was achieved. It also reduced DED symptoms and had a very good safety profile. Conclusions: the study formulation produced a significant improvement in the signs, symptoms, and QoL of patients with mild to moderate DED with a good safety profile after 1 month of treatment. [ABSTRACT FROM AUTHOR]

To compare two types of lipid expression procedures to treat dry eye disease. Standardized treatment and evaluation methods were used in patients treated with either manual thermoelectric lipid expression (MiBoFlo) or automated lipid expression (Lipiflow) of the Meibomian glands. This was a contemporaneous, non-randomized study of both treatment methods. Treatment was per the manufacturers’ recommendation. The primary outcome included two types of dry eye questionnaires as well as objective analysis of ocular surface including tear break up time, Schirmer testing, Osmolarity, and fluorescein staining. Baseline characteristics analyzed included floppy lid, conjunctivochalasis and lagophthalmos. Statistical analysis was performed correcting for baseline factors such as age and co existing pathology using multivariable analysis. Both treatments improved the results of the OSDI and SPEED dry eye questionnaire results. Both treatments resulted in improvement of many objective findings including SPK, lissamine green staining and tear break up time with the MiBoFlo showing more improvement than Lipiflow. OSDI was more sensitive to improvement of symptoms than the SPEED questionnaire. Manual expression with MiBoFlo device resulted in statistically more improvement in questionnaire scores than did automated expression with Lipiflow. Negative prognostic factors for symptomatic improvement included blepharitis, autoimmune disease and ocular allergies. Thermal lid therapy along with mechanical expression of lipids from the meibomian glands successfully treats dry eye symptoms and signs. Manual therapy with MiBoFlo resulted in more subjective and objective improvement scores than automated therapy with the Lipiflow device. [ABSTRACT FROM AUTHOR]

One of the main roles of the lipid layer (LL) of the tear film (TF) is to help prevent evaporation of the aqueous layer (AL). The LL thickness, composition, and structure all contribute to its barrier function. It is believed that the lipid layer is primarily nonpolar with a layer of polar lipids at the LL/AL interface. There is evidence that the nonpolar region of the LL may have liquid crystalline characteristics. We investigate the structure and function of the LL via a model of the tear film with two layers, using extensional flow of a nematic liquid crystal for the LL and shear-dominated flow of a Newtonian AL. Evaporation is taken into account and is affected by the LL thickness, internal arrangement of its rod-like molecules, and external conditions. We conduct a detailed parameter study with a focus on the evaporative resistance parameter, the Marangoni number, and primary liquid crystal parameters including the Leslie viscosities and director angle. This new model responds similarly to previous Newtonian models in some respects; however, incorporating internal structure via the orientation of the liquid crystal molecules affects both evaporation and flow. As a result, we see new effects on TF dynamics and breakup. [ABSTRACT FROM AUTHOR]

Dry eye syndrome (DES) is a tear film disorder caused by increased tear evaporation or decreased production. The heavy workload on the eye and the increased usage of digital screens may decrease blink frequency, leading to an increased evaporation rate and an upsurge in the incidence and severity of DES. This study aims to assess the severity of DES symptoms and the risk factors among university students. A cross-sectional study was conducted at Umm AlQura University to evaluate the severity of DES among students and explore its potential association with digital screen use. Validated questionnaires were used to assess the severity of DES and digital screen usage. The study included 457 participants, of which 13% had symptoms suggestive of severe DES. Furthermore, multiple risk factors had a significant association with the severity of DES, including gender, use of monitor filters, monitor and room brightness, and smoking habits. DES symptoms were prevalent among university students, particularly female students. Although there was no significant association with the duration of screen usage and collage distribution. Other factors however, such as the usage of screen monitors and the brightness of both the monitor and the room, were significantly associated with the severity of DES symptoms. [ABSTRACT FROM AUTHOR]

Herpes zoster (HZ) is caused by reactivation of latent infection of varicella zoster virus (VZV) in sensory (cranial, dorsal root) ganglia. Major risk factors for HZ are increasing age and immunosuppression. HZ ophthalmicus (HZO) is a subset of HZ with involvement of the ophthalmic division of the fifth cranial trigeminal nerve. Approximately 4–20% of patients with HZ develop HZO. Approximately 50% of patients with HZO develop ocular disease, among whom up to 25% develop chronic or recurrent disease. Common manifestations of ocular disease include conjunctivitis, keratitis, and uveitis, whereas optic neuropathy and retinitis are uncommon. Due to the potential for vision impairment, ocular involvement requires urgent ophthalmic consultation. Early recognition and timely treatment with antivirals may prevent ocular complications. HZO is preventable by vaccination against HZ. Vaccine efficacy/effectiveness studies have been largely conducted for HZ with few studies assessing HZO. Both the recombinant adjuvanted vaccine (RZV) and live-attenuated vaccine (ZVL) significantly reduce the incidence of HZ and HZO in older adults. RZV is more effective than ZVL. Data on the effectiveness of vaccines for prevention of recurrent disease in patients with HZO are limited; however, vaccination is recommended. Despite recommendations to vaccinate individuals likely to benefit from an HZ vaccine, coverage for adults remains suboptimal. Barriers to vaccination include patient beliefs about HZ or HZ vaccines, and factors related to healthcare providers. In particular, the lack of a recommendation from their primary care physician is often cited by patients as a reason for remaining unvaccinated. By encouraging vaccination against HZ, physicians not only prevent HZ and HZO but also potential vision loss due to HZO. Graphical abstract available for this article. Plain Language Summary: Shingles, also known as herpes zoster, is a common and painful rash that develops when the virus that causes chickenpox in children reactivates, most often in adults. When shingles affects the eye or the area surrounding the eye, it is called herpes zoster ophthalmicus, or HZO for short. Up to one-fifth of people with shingles have HZO, and this risk increases with age and in people with other conditions that affect their immune system. Common signs and symptoms include a rash on the face, pain, fever, and headache, as well as symptoms in the eye, such as discomfort, redness, and discharge. HZO has the potential to cause permanent vision loss, and because of this, it is important that people with symptoms are referred to an eye doctor ("ophthalmologist") as soon as possible. Early diagnosis of HZO is essential for effective treatment and prevention of the more serious complications it can cause. Treatment within 3 days of the symptoms occurring, with medications known as antivirals, can shorten the duration of a shingles episode and help relieve the pain. To help prevent the risk of shingles and its subtypes like HZO, vaccination is recommended. Two vaccines are currently approved for the prevention of shingles in adults. Although these vaccinations are recommended, some people do not have them for various reasons, which include their own personal beliefs about vaccinations or that their doctor has not recommended it to them. It is important that vaccinations against shingles are recommended to all patients eligible to receive one. [ABSTRACT FROM AUTHOR]

Introduction: To assess the efficacy and safety of the combination of microblepharoexfoliation (MBE), intense pulse light (IPL) and meibomian gland expression (MGX) for treatment of meibomian gland dysfunction (MGD). Methods: This was a prospective, parallel-control trial conducted from April 2022 to January 2023. Participants were assigned to receive either three sessions of MBE-IPL-MGX treatment and home-based therapy (treatment group) or home-based therapy alone (control group). Outcome measures were assessed at baseline and after 2-month follow-up. Results: Seventy eyes of 70 patients were enrolled. MBE-IPL-MGX treatment achieved better improvements than home-based therapy in ocular surface disease index (OSDI) and symptom assessment in dry eye (SANDE) scores, noninvasive tear film break-up time (NIBUT), lipid layer grade (LLG), loss area meibomian gland (LAMG) and meibomian gland yielding secretion score (MGYSS). The mean differences between the two groups were as follows: OSDI (– 11.23 ± 4.68 points, P < 0.001), SANDE (– 24.63 ± 13.41 points, P < 0.001), NIBUT (1.3 ± 1.57 s, P = 0.033), LLG (0.4 ± 0.04 points, P = 0.003), LAMG (– 2.85 ± 1.69%, P = 0.023) and MGYSS (7.5 ± 2.32 points, P < 0.001). In addition, the increment (Δ) of MGYSS after MBE-IPL-MGX treatment was significantly higher in MGD grades 2 and 3 (all P < 0.001). Conclusions: MBE-IPL-MGX treatment is an effective and well-tolerated procedure that improves dry eye symptoms and signs as well as meibomian gland secretions in patients with MGD. In addition, this treatment is recommended for MGD grades 2 and 3. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of different pterygium surgery techniques on ocular surface (OS) in different follow-up periods. Methods: PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, and China Biology Medicine disc were searched for studies reporting pre- and post-operative OS parameters in pterygium. Results: A total of 33 articles were finally included. Three OS parameters showed relatively consistent changing trends after surgery including ocular surface disease index (OSDI), tear film break-up time (BUT), and score of corneal fluorescein staining (SCFS). They worsened significantly at 1w post-operation and then gradually improved: OSDI and BUT showed obvious improvement in 1 m post-operation (SMD = − 0.58, 95%CI = [− 1.04, − 0.13]; SMD = 0.42, 95%CI = [0.06, 0.78]); SCFS was restored to preoperative levels in 3 m after surgery (SMD = − 0.54, 95%CI = [− 1.16, 0.07]). Another parameter, Schirmer test without anesthesia (SIT), presented transient increase at 1w post-operation (SMD = 0.87, 95%CI = [0.27, 1.47]) and presented a relatively stable improvement after 1 m post-operation (SMD = 0.52, 95%CI = [0.16, 0.89]). All parameters in amniotic membrane graft (AMT) showed better improvement in early stage and they showed non-inferior improvements in the long term compared with conjunctival autograft (CAG). Limbal-conjunctival autograft (LCAG) made excellent improvement to OS in the long term while pterygium excision (PE) showed the worst OS. The type of pterygium (primary and secondary), diabetes mellitus (DM) status, and fixation method had certain effects on the results. Conclusions: OS of pterygium is deteriorated at 1w post-operation then gradually improved to preoperative levels after 1 m post-operation. Among various surgery techniques, LCAG had the best improvement to OS which especially displayed in the long-term outcomes. [ABSTRACT FROM AUTHOR]

Approximately 1% of all patients with Sjögren's syndrome (SS) are children. Unlike the adult form, in which sicca syndrome is the main presentation, in children, the most common clinical finding is recurrent enlargement of the salivary glands. In pediatric SS, extraglandular manifestations represent a significant feature and, among these, kidney manifestations are relevant. Kidney involvement is observed in 5–20.5% of children with SS, most frequently tubulointerstitial nephritis. This injury can lead to serious phenotypes, including distal kidney tubular acidosis with the development of severe hypokalemia, which can lead to ECG abnormalities, weakness, and hypokalemic periodic paralysis. Kidney implications in pediatric SS also include nephrolithiasis, nephrocalcinosis, and various types of glomerular damage, which often require immunosuppressive therapies. Laboratory findings are usually comparable to adults, including hyperglobulinemia and high rates of antinuclear antibodies (ANA, 63.6–96.2%), and anti-Ro/SSA (36.4–84.6%). The current classification criteria for SS are inaccurate for the pediatric population, and more specific criteria are needed to improve the diagnostic rate. Due to the rarity of the disease, strong recommendations for treatment are lacking, and several therapeutic strategies have been reported, mostly based on glucocorticoids and disease-modifying antirheumatic drugs, with different outcomes. The aim of this paper is to provide an overview of the kidney implications of pediatric SS based on the latest evidence of the medical literature. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the efficacy and safety of Quantum Molecular Resonance (QMR) treatment in patients with severe dry eye disease (DED), as well as its effects on aqueous-deficient (ADDE), evaporative (EDE), and mixed (MDE) dry eye. Methods: In this prospective, interventional study, 81 patients were randomly allocated to received four treatment sessions of QMR at 1-week intervals (Rexon-Eye®, Resono Ophthalmic, Trieste, Italy) (QRM group) or tear substitute four times daily, containing 0.15% sodium hyaluronate and 3% trehalose (Thealoz Duo®, Thea Pharma, France) (SH-TH group). Outcome measures included ocular surface disease index (OSDI) questionnaire, tear meniscus height (TMH), tear breakup time (TBUT), non-invasive breakup time (NIBUT), corneal fluorescein staining (CFS), lipid layer thickness (LLT), tear film osmolarity (OSM), and meibomian gland dysfunction (MGD) grade, which were assessed at baseline and 1-month and 3-month follow-up. Results: The QMR group achieved better improvements than the SH-TH group in OSDI and SANDE questionnaires, NIBUT, LLT, and CFS. The mean differences between the groups were as follows: OSDI (− 12.4 ± 0.25 points, P = 0.01), SANDE (10.6 ± 1.7 points, P = 0.01), NIBUT (2 ± 0.25 s, P = 0.01), LLT (18.7 ± 0.7 nm, P = 0.01), and CFS (1.2 ± 0.1 points, P = 0.02). In subgroups analysis, QMR treatment demonstrated a beneficial role to improve DED symptoms and signs in ADDE, EDE, and MDE. Conclusion: QMR is an effective and well-tolerated treatment that seems to improve DED symptoms and signs in patients with severe DED. However, further studies are needed to confirm this. Trial Registration: ClinicalTrials.gov identifier NCT06119386. [ABSTRACT FROM AUTHOR]

Introduction: The study aimed to evaluate multi-symptom relief of dry eye manifestations with the use of propylene glycol-hydroxypropyl-guar (PG-HPG) nanoemulsion lubricant eye drops, among subjects with dry eye disease (DED). Methods: This was a post-marketing, prospective, single-arm study conducted in the USA. Subjects aged ≥ 18 years, with tear breakup time (TBUT) ≤ 10 s for both eyes, dry eye questionnaire-5 (DEQ-5) "watery eyes" symptom score 1–4, symptoms of burning/stinging, sore and tired eyes as determined by impact of dry eye on everyday living—symptom bother (IDEEL-SB) questionnaire, and IDEEL-SB score 16–65 were included. Subjects were required to complete IDEEL-SB and DEQ-5 at days 0, 14 ± 2, and 28 ± 2, and self-administer one drop of PG-HPG four times daily for 28 ± 2 days. Primary endpoints were change from baseline at day 28 in symptoms of sore, stinging/burning, and tired eyes on IDEEL-SB; and symptom of watery eyes on DEQ-5. Other endpoints evaluated were corneal staining and TBUT at baseline and day 28 ± 2; symptom relief (5-point Likert scale) at day 28 ± 2, and safety. Results: Of 119 subjects enrolled, 95 completed the study (mean ± SD age 61.2 ± 13.0 years; female 69.5%). Mean IDEEL-SB scores reduced significantly from baseline at day 28 for symptoms of aching/sore eyes (change from baseline − 1.0 ± 1.1), burning/stinging eyes (change from baseline − 1.1 ± 0.9), and tired eyes (change from baseline − 1.1 ± 1.0) (all p < 0.0001). Mean DEQ-5 score for watery eye symptoms significantly reduced from baseline at day 28 (change from baseline − 0.9 ± 1.0, p < 0.0001). Corneal staining at day 28 was comparable to baseline. TBUT improved from baseline to day 28. On a Likert scale, more than 50% of subjects reported relief from symptoms of sore, stinging, and burning eyes. Three (3.1%) subjects reported treatment-emergent adverse events (non-ocular). Conclusions: PG-HPG nanoemulsion lubricant eye drops significantly improved multiple dry eye symptoms in subjects with DED over 28 days, with no new safety concerns. Trial Registration: ClinicalTrials.gov Identifier, NCT05056155. [ABSTRACT FROM AUTHOR]

Purpose: To explore the long-term course of patients with meibomian gland dysfunction (MGD), and to analyse potential factors affecting the recovery of meibomian gland (MG) dropout. Methods: Seventy-nine MGD patients (79 eyes) aged 36.03±15.78 years old who underwent more than one year of follow-up were enrolled in this retrospective study. Corneal fluorescein staining (CFS), tear meniscus height (TMH), noninvasive breakup time (NIBUT), and noncontact meibography at baseline and last visit were collected and analysed. Then an automatic MG analyzer was used to measure the morphological and functional parameters of MGs, including their area ratio (AR), tortuosity index (TI), and signal index (SI). The patients whose AR increased by more than 5% were defined as MG improvement, and AR decreased by more than 5% was MG worsening. Results: A total of 79 patients (79 eyes) were assessed with at least 1-year of follow-up. More than 1/3 of MGD patients (27 eyes, 34.2%) underwent MG improvement, and 30.4% of MGs became worsened. Age (P=0.002), gender (P<0.001), IPL treatment (P=0.013), the change of CFS (P=0.0015), and the recovery of SI (P=0.035) showed significant differences among different recovery groups. Age(P<0.001), female sex (P=0.003), ΔCFS (P<0.001), AR at baseline (P<0.001) were negative correlation with AR recovery, and the change of SI (P=0.003) and IPL treatment (P=0.003) had a positive correlation with it. Among them, age (P=0.038), the change of CFS (P=0.004), and AR at baseline (P=0.007) were confirmed as negatively correlated factors predicting the long-term change of the MG. Conclusion: Although the MGD treatment has continued for more than 1 year, only 34.2% of MGD patients were observed to undergo MG improvement. Younger patients and patients with better CFS recovery seem to have more opportunities to improve their MGs. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease (DED) is a common tear film disorder caused by decreased tear production or increased tear evaporation. The increased use of computers in the workplace has brought about the development of ocular health concerns, including dry eye disease. Therefore, this study was designed to determine the prevalence of DED associated with computer work and recommend preventing or reducing its development. This study investigated the prevalence of DED among IT students in Dera Ghazi Khan. Methods: A cross-sectional descriptive study was conducted among 327 undergraduate students of the IT department in the district of Dera Ghazi khan over 5 months from September 2021 to January 2022. DED was assessed subjectively with Ocular Surface Disease Index. Data were analysed using SPSS version 21. The quantitative analysis was presented as mean and standard deviation, and qualitative variables were introduced in frequency and percentages. The chi-square test (Fisher’s exact test) was used to study the significance of associations between dependent and independent variables. Results: The mean age of the participants was 20.25 ± 1.305 years (range 17–25). The prevalence of DED among computer programmers was 47.7%. This study showed that gender (p = 0.31), contact lens usage (p = 0.64), and duration of time spent on computer display units (p = 0.47) were not significant determinants of DED among computer programmers. Conclusion: DED is prevalent among IT students, along with different symptoms. However, further studies are required to adequately measure the prevalence of DED during longer exposure time to computer screens and explore environmental risk factors. [ABSTRACT FROM AUTHOR]

Purpose: To investigate dry eye disease (DED) in newly diagnosed patients with depressive disorder (MDD). Method: This observational study included 48 MDD patients in Group 1 and 20 healthy controls in Group 2. Psychiatric and ophthalmic examinations, Beck Depression Inventory (BDI), Ocular Surface Disease Index (OSDI), Schirmer's test, tear breakup time (TBUT), Meibomian gland dysfunction (MGD), and ocular staining were conducted. The results were statistically compared. Results: The participants, comprising 32 men and 36 women, had a mean age of 31.08 ± 11.7 years (18–64 years). Group 1 had a mean BDI score of 30.87 ± 8.56, while Group 2 had a score of 1.3 ± 1.3 (p < 0.001). In Group 1, 28 patients were diagnosed with DED, whereas in Group 2, six subjects were diagnosed with DED. The mean Schirmer's results in Group 1 and Group 2 were (mm/5 min) 10.87 ± 2.44 and 12.70 ± 2.3, respectively, and were significantly lower in Group 1 (p < 0.001). The mean OSDI scores in Group 1 (34.95 ± 15.8) were significantly higher compared to Group 2 (3.2 ± 3.1) (p < 0.001). There was no significant difference in mean TBUT between Group 1 (9.41 ± 2.6 s) and Group 2 (9.8 ± 0.61 s) (p > 0.05). Significant correlations were found between BDI scores and Schirmer's results as well as OSDI scores (p < 0.05, p = 0.02, respectively). No statistically significant correlations were found between BDI scores and TBUT or MGD (p > 0.05). Conclusion: DED was found to be more prevalent in the MDD group. The severity of MDD and DED, as indicated by BDI, OSDI, and Schirmer's results, was found to be correlated. It was observed that patients with higher depression scores had more severe dry eye. As a result, we recommend performing ophthalmic examinations in newly diagnosed MDD patients. [ABSTRACT FROM AUTHOR]

Purpose: Dry eye disease (DED) is a prevalent ocular surface disease that is conventionally characterized by tear film hyperosmolarity and instability. This review presents a summarized classification of DED, followed by a comprehensive discussion of the most recent topical and systemic medications and clinical recommendations for selecting the most appropriate option for each patient. Methods: An extensive literature search was conducted on electronic databases, such as PubMed, Scopus, and Web of Science, using keywords including “dry eye syndrome,” “ocular surface disease,” “medical management,” “artificial tears,” “topical immunomodulators,” and “meibomian gland dysfunction.” Results: The underlying reasons for DED can range from insufficient aqueous tear production to increased tear evaporation. Recent literature has provided a more in-depth understanding of the pathophysiology of DED by examining the tear film's lipid, aqueous, and mucin layers. However, despite these advancements, medical management of patients with symptomatic DED has not fully reflected this modernized knowledge of its pathophysiology. Conclusion: To develop a rationalized strategy for treating DED, it is crucial to have updated knowledge of therapeutic options, their mechanisms of actions, and indications based on the DED type and underlying causes. [ABSTRACT FROM AUTHOR]

Purpose: The present study aims to evaluate the optic nerve, macula, and choroidal changes in both rheumatoid arthritis (RA) and primary Sjögren’s syndrome (SjS) patients, and to compare these findings with age-matched healthy volunteers. Methods: This study included 46 RA patients, 33 primary SjS patients, and 37 age-matched healthy volunteers. All of the patients underwent a thorough ophthalmological examination, during which measurements of the retinal nerve fiber layer (RNFL), ganglion cell layer(GCL), and subfoveal choroidal thickness (CT) were taken using OCT (optical coherence tomography). The measurements taken from the right eye of each patient were used to compare among the groups. Results: RNFL thickness in superior quadrant was found to be statistically significantly thinner in the eyes with RA when compared to the control group (p = 0.022). In the nasal quadrant, the RNFL thickness was significantly thinner in patients with primary SjS compared to healthy individuals (p = 0.036). Also, the temporal quadrant RNFL was significantly thinner in RA patients than in the primary SjS patients (p = 0.033). GCL thickness was observed to be thinner in all quadrants of both RA and primary SjS groups compared to the control group. However, the difference was not found to be statistically significant. Subfoveal CT was observed to be thicker in RA and SjS groups compared to the control group, but this difference was also not statistically significant. Conclusion: Systemic autoimmune diseases like RA and primary SjS can lead to a decrease in RNLF and GCL thickness, which can impair visual acuity even in the absence of ocular symptoms. Therefore, monitoring changes in the optic nerve, retina, and choroid layer are crucial in these patients. [ABSTRACT FROM AUTHOR]

Dysregulation of oxidative stress serves as a pivotal predisposing or exacerbating factor in the intricate development of numerous pathological processes and diseases. In recent years, substantial evidence has illuminated the crucial role of reactive oxygen species (ROS) in many fundamental cellular functions, including proliferation, inflammation, apoptosis, and gene expression. Notably, producing free radicals within ROS profoundly impacts a wide range of biomolecules, such as proteins and DNA, instigating cellular damage and impairing vital cellular functions. Consequently, oxidative stress emerges as a closely intertwined factor across diverse disease spectra. Remarkably, the pathogenesis of several eye diseases, including age-related macular degeneration, glaucoma, and diabetic retinopathy, manifests an intrinsic association with oxidative stress. In this comprehensive review, we briefly summarize the recent progress in elucidating the intricate role of oxidative stress in the development of ophthalmic diseases, shedding light on potential therapeutic avenues and future research directions. [ABSTRACT FROM AUTHOR]

Introduction: An innovative eye drops formulation containing 0.2% hyaluronic acid and a low concentration of hydrocortisone (0.001%; hereafter HALH) has been recently placed on the market (Idroflog®, Alfa Intes, Italy) to manage the dysregulated parainflammation in patients with dry eye disease (DED). In the present paper, the effectiveness of HALH on the signs and symptoms of DED was retrospectively evaluated and compared with that one obtained using standard tear substitutes (STS) by means of low- and high-tech (Keratograph®) assessments. Methods: This was a multicenter retrospective study carried out between February and April 2023, involving adult patients with DED diagnosis owing to post-cataract surgery, meibomian gland dysfunction, allergy, or glaucoma medications. The primary aim was to compare the changes induced by different therapies on Keratograph® parameters (noninvasive Keratograph tear breakup time [NIKBUT], tear meniscus height [TMH], eyelid meibography, conjunctival hyperemia, and conjunctivochalasis) or collected by traditional low-tech measures (tear breakup time [TBUT], Schirmer test, Efron score, and epithelial alterations) and the Ocular Surface Disease Index score. Results: Data from 155 patients were analyzed. The effectiveness of HALH and STS was reported by both high- and low-tech measures. NIKBUT-first showed a significant improvement in the HALH group versus the STS one at 15 days (6.4 ± 3.6 vs 5.4 ± 3.7 s, p = 0.02), whereas this difference was latent with low-tech TBUT until 45 days (6.8 ± 2.6 vs 5.6 ± 2.3 s, p = 0.03). Patients with DED occurring after cataract surgery reported an enhanced activity of HALH versus STS, particularly for NIKBUT-first, TMH, Schirmer test, and hyperemia stage. Conclusion: These findings highlighted the effectiveness of HALH in all DED subtypes, especially in patients with post-cataract surgery, as well as its superiority versus STS in terms of tear film stability improvement. We recommend longer observation (i.e., 3–6 months) to fully ascertain whether the early improvement detected by high-tech measures will be confirmed in subsequent time points even using low-tech tests. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to compare the ocular surface temperature in keratoconus eyes with that in normal eyes. Methods: A total of 27 participants were enrolled, with 10 and 17 participants in the keratoconus and control groups, respectively. Participants in the control group underwent an ophthalmic slit lamp examination and ocular thermography, while an additional corneal tomography was performed for those in the keratoconus group. Results: For patients with keratoconus, the mean upper eyelid temperature (UET) was 32.36 ± 1.02 °C, inner canthus temperature (ICT) was 34.25 ± 0.83 °C, outer canthus temperature (OCT) was 33.62 ± 0.96 °C, initial central corneal temperature (initial CCT) was 33.04 ± 1.03 °C, sixth-second CCT (6 s-CCT) was 32.67 ± 1.19 °C, and the mean change in CCT measured within 6 s (change in CCT within 6 s) was 0.36 ± 0.26 °C. For controls, the values for UET, ICT, OCT, initial CCT, 6 s-CCT, and change in CCT within 6 s were 32.35 ± 1.13 °C, 34.14 ± 0.91 °C, 33.51 ± 1.02 °C, 33.22 ± 1.01 °C, 32.99 ± 1.01 °C, and 0.22 ± 0.17 °C, respectively. Except for the change in CCT within 6 s (p = 0.022), no significant differences were observed in UET (p = 0.973), ICT (p = 0.659), OCT (p = 0.697), initial CCT (p = 0.556) or 6 s-CCT (p = 0.310) between the two groups. Conclusion: The keratoconus eyes showed faster changes in CCT and evaporation of tear film after opening the eyes. Therefore, the keratoconus eyes had a higher incidence of dry eye conditions. [ABSTRACT FROM AUTHOR]

Topical glaucoma medications are effective and safe, but they have numerous well-documented limitations that diminish their long-term utility and sustainability. These limitations can include high rates of nonadherence (with associated glaucoma progression), concerning side effects, inconsistent circadian intraocular pressure (IOP) control, complex dosing regimens, difficulty with self-administration, costs, and decreased quality of life. Despite these limitations, topical medications traditionally have been first-line in the glaucoma treatment algorithm, as no other minimally invasive treatment alternatives existed. In recent years, however, novel interventional therapies—including sustained-release drug-delivery platforms, selective laser trabeculoplasty, and micro-invasive glaucoma surgery procedures—have made it possible to intervene earlier without relying on topical medications. As a result, the topical medication-first treatment approach is being reevaluated in an overall shift toward earlier more proactive interventions. [ABSTRACT FROM AUTHOR]

We compared the efficacy and safety of autologous-serum (AS) and platelet-rich plasma (PRP) eye drops for dry eye (DE) treatment in primary Sjögren's syndrome (SS). This prospective, randomized, double-blinded clinical study included patients diagnosed with primary SS DE. Thirty-eight participants were randomly assigned to the AS or PRP groups. Corneal and conjunctival staining scores, Schirmer I test, tear film break-up time (TBUT), and ocular surface disease index (OSDI) scores were evaluated at 4 and 12 weeks. Conjunctival impression cytology (CIC) metaplasia grade and goblet cell density grade at 12 weeks were compared with those at baseline. Corneal and conjunctival staining scores and TBUT significantly improved at 4 and 12 weeks in both groups (all p < 0.005). No significant difference between the AS and PRP groups was observed at 4 and 12 weeks. The Schirmer I values, OSDI scores, CIC metaplasia grade, and goblet cell density grade did not significantly change at 4 and 12 weeks in either group. Both AS and PRP eye drops are effective for primary SS DE without a significant difference. Considering that the preparation time of PRP is shorter than that of AS, PRP can be a good alternative treatment for primary SS DE. [ABSTRACT FROM AUTHOR]

Purpose: Our study aimed to make a bibliometric analysis on Sjögren's syndrome-related dry eye disease (SS-DED), explore its potential research hotspots, and provide critical information for future research interest and undeveloped topics in this field, which can benefit clinicians and researchers. Methods: We extracted all publications relating to SS-DED from 2003 to 2022 from the Web of Science Core Collection database. Original articles and reviews in English were included. The contributions of different countries, institutions, journals, and authors were compared, and the research hotspots were visualized for network analysis through GraphPad Prism, CiteSpace, and VOSviewer. Results: We enrolled a total of 987 publications. The United States contributed the most publications (281, 28.5%), followed by China (157, 15.9%) and Japan (80, 8.11%). Publications from the United States were cited more frequently (13,060 citations), with the highest H-index of 57. China ranked second in the total number of publications, the papers were not cited frequently (3790 citations), and the H-index ranked second (H-index = 31). PLoS One (32, 3.24%) published the most papers, and the University of California system had the highest number of publications (45, 4.56%). Bootsma H from the Netherlands published the most papers. The trend of research hotspots evolved mainly from the basic manifestation to pathogenesis and treatment of SS-DED and paid more attention to distinguishing SS-DED from that dry eye disease without SS. Conclusions: Based on the bibliometric, co-citation, and network analyses in this study, we obtained the annual publications and citations, the growth trends of publications, the productivity of countries, organizations, journals, and authors, high-quality publications, and the emerging hotspots of SS-DED, which may open new doors for promising research directions. [ABSTRACT FROM AUTHOR]

Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs' metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis. [ABSTRACT FROM AUTHOR]

Many candidate drugs for dry eye disease (DED) have been assessed over the years in pursuit of demonstrating efficacy in both signs and symptoms. However, patients with DED have very limited treatment options for management of both signs and symptoms of DED. There are several potential reasons behind this including the placebo or vehicle response, which is a frequent issue observed in DED trials. A high magnitude of vehicle response interferes with the estimation of a drug's treatment effect and may lead to failure of a clinical trial. To address these concerns, Tear Film and Ocular Surface Society International Dry Eye Workshop II taskforce has recommended a few study design strategies to minimize vehicle response observed in DED trials. This review briefly describes the factors that lead to placebo/vehicle response in DED trials and focuses on the aspects of clinical trial design that can be improved to mitigate vehicle response. In addition, it presents the observations from a recent ECF843 phase 2b study, wherein the study design approach consisted of a vehicle run-in phase, withdrawal phase, and masked treatment transition, and led to consistent data for DED signs and symptoms and reduced vehicle response post randomization. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the applicability of lower lid margin thickness (LLMT) measurements in adults with and without meibomian gland dysfunction (MGD) by optical coherence tomography (OCT) and keratograph. Methods: This is a cross-sectional, observational study. A hundred and eight volunteers aged 20 to 79, including 68 MGD patients and 40 normal subjects, were recruited. Using OCT and keratograph to measure the LLMT from the posterior lash line to anterior edge or outer edge of the tear meniscus was separately performed two times by the same person. Results: The mean age of normal and MGD subjects was 50.5 ± 14.2 years and 55.8 ± 15.5 years, respectively. The LLMT with OCT and keratograph in MGD patients was significantly greater than that in normal subjects (1.06 ± 0.27 and 1.03 ± 0.25 mm vs. 0.90 ± 0.20 and 0.86 ± 0.16 mm, respectively). In both normal and MGD subjects, the tear meniscus height and LLMT with OCT were both greater than that with keratograph (P < 0.05), and intraclass correlation coefficient (ICC) demonstrated a good agreement in the LLMT measurements between two devices (ICC = 0.83 and 0.79, respectively). Additionally, the LLMT in MGD patients was appeared to be positively correlated with meiboscore (rs = 0.37, P = 0.002). Conclusions: The OCT and keratograph were two reliable tools in the LLMT measurements, which may have potential applications for diagnosis and evaluation of MGD. Furthermore, we found that the LLMT measured by OCT was greater than that measured by keratograph. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a challenge in ophthalmology. Rat models represent valuable tools to study the pathophysiology and to develop novel treatments. A major challenge in DED research is detecting multiple biomarkers in a low tear volume sample. Multiplex immunoassays for DED rat research are missing. We have developed a multiplex electrochemiluminescence immunoassay (ECLIA) to detect three biomarkers for DED: MMP-9, IL-17 and ICAM-1. Tears, used as matrix, were collected from six healthy Wistar rats. Assays were run based on the U-Plex Meso Scale Diagnostics (MSD) platform, by two independent operators according to the EMA guideline on bioanalytical method validation. Linear mixed, regression models were fit to perform the statistical analysis on the range of concentrations for the chosen analytes. During optimization, it has observed that incubation time, temperature and agitation affected the robustness of the protocol. ECLIA optimum conditions include the use of antibodies at 0.5 µg/ml concentration and 1 h incubation at room temperature with shaking. Precision met the acceptance criteria in the chosen range: 1062–133 pg/ml for ICAM-1, 275–34.4 pg/ml for IL-17, 1750–219 pg/ml for MMP-9. Accuracy and linearity were acceptable for a broader range. This is the first report of a validated ECLIA that allows measurements of three relevant DED biomarkers in rat tear fluids. [ABSTRACT FROM AUTHOR]

Inflammation is a key factor in the pathogenesis of dry eye disease (DED). We aimed to investigate the role of microRNA-146a (miR-146a) in regulating corneal inflammation in a mouse model of benzalkonium chloride (BAC)-induced dry eye and the TNF-α-induced NF-κB signaling pathway in human corneal epithelial cells (HCECs). A mouse model of dry eye was established by administering with BAC to BALB/c mice, and the expression of TNF-α, IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) in the corneas of dry eye model mice was significantly increased; this was accompanied by the upregulation of miR-146a and activation of the NF-κB pathway. In vitro, TNF-α induced miR-146a expression in HCECs, while the NF-κB inhibitor SC-514 reduced the expression of miR-146a. Overexpression of miR-146a decreased the expression of IRAK1 and TRAF6, which have been identified as targets of miR-146a. Furthermore, overexpression of miR-146a suppressed NF-κB p65 translocation from the cytoplasm to the nucleus. Moreover, overexpression of miR-146a attenuated the TNF-α-induced expression of IL-6, IL-8, COX2 and intercellular adhesion molecule 1 (ICAM1), while inhibition of miR-146a exerted the opposite effect. Our results suggest that miR-146a mediates the inflammatory response in DED. MiR-146a negatively regulates inflammation in HCECs through the IRAK1/TRAF6/NF-κB pathway, and this may serve as a potential therapeutic approach for the treatment of DED. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease (DED), Meibomian gland dysfunction (MGD), and Sjögren's syndrome dry eye disease (SS-DED) are eye dryness conditions that show significant overlap in various symptoms of ocular discomfort. The aim of this study was to qualitatively explore the patient experience and evaluate content validity of the newly developed Dry Eye Disease Questionnaire (DED-Q). Methods: Semi-structured interviews were conducted with 61 US adults who reported experiencing ocular symptoms due to their physician-confirmed primary diagnosis of DED (n = 21), MGD (n = 20), or SS-DED (n = 20). The open-ended concept-elicitation phase was followed by cognitive debriefing (CD) of the DED-Q to evaluate participants' understanding and relevance of the instructions, items, response options, and recall periods. Interviews were also conducted with eight specialist healthcare professionals to assess clinical relevance of the concepts included. Verbatim interview transcripts were analyzed using thematic analysis in ATLAS.ti v8 software. Results: A total of 29 symptoms and 14 impacts on quality of life were reported across participant interviews. Primary ocular symptoms reported included eye dryness (n = 61/61; 100%), eye irritation (n = 55/61; 90%), eye itch (n = 54/61; 89%), burning sensation (n = 52/61; 85%), and foreign body sensation (n = 51/61; 84%). The most impacted aspects of daily life were using digital screens (n = 46/61; 75%), driving (n = 45/61; 74%), working (n = 39/61; 64%), and reading (n = 37/61; 61%). CD findings showed most participants had good understanding of DED-Q items and confirmed most concepts were relevant to the lived experience of their condition. Aside from few minor changes to the items and examples to facilitate more accurate interpretation, the proposed instruction wording was modified for various symptom and impact modules to encourage participants to focus only on dry eye vision problems. Conclusions: This research identified multiple prevalent symptoms and impacts of DED, MGD, and SS-DED, most of which were similar across the conditions. The DED-Q was confirmed to be a content-valid PRO measure suitable for use in clinical studies to assess the patient experience of DED, MGD, and SS-DED. Future work will focus on evaluating the psychometric properties of the DED-Q for use as an efficacy endpoint in clinical trials. Plain English summary: Dry Eye Disease (DED), Meibomian Gland Dysfunction (MGD), and Sjögren's Syndrome Dry Eye Disease (SS-DED) are conditions related to dryness of the eye. There is no suitable patient-reported outcome (PRO) measure available for use across the three conditions. Interviews were conducted with 61 participants with any of the three conditions to understand the symptoms they experience and their impact on daily life. The findings were used to refine the content of a new PRO measure, the Dry Eye Disease Questionnaire (DED-Q). To evaluate the suitability of the DED-Q, participants were also asked to complete each item of the DED-Q during the interview and share their understanding of the item wording, response options and the recall period. Interviews were also conducted with eight healthcare professionals (HCPs). The main symptoms reported by the patients across three conditions were eye dryness, eye irritation, eye itch, burning sensation, and foreign body sensation. The symptoms caused difficulties in performing activities such as using digital screens, driving, working, and reading. Almost all participants demonstrated good understanding of the items on the DED-Q and found them to be relevant to their experience of their condition. The HCPs also confirmed that the concepts covered in the DED-Q were relevant to assess the participant experience across these conditions. Next steps will involve a more detailed analysis of the measurement properties of the DED-Q to confirm its usefulness in supporting primary or secondary endpoints in clinical trials. [ABSTRACT FROM AUTHOR]

In the recent years, multiscale fibres have gained widespread attention for use in diverse biomedical applications. With the technological advancements in electrospinning technique, the dimensions of the multiscale fibres can be tailored to match the desired requirements of the target tissues and organs. These fibres combining the unique properties of nano- and microfibres can be fabricated several techniques. The engineered multiscale fibrous scaffolds are being utilised to deliver growth factors and cells of interest, thereby, aid in tissue regeneration. The elastic modulus of the multiscale fibrous scaffolds can be enhanced by introducing biomaterials like multilayer carbon nanotubes (MCNT), nanoclay, nanohydroxyapatite (n-HAp), and graphene oxide (GO). Moreover, studies on bone, cartilage, cardiovascular and liver tissue engineering have revealed that the multiscale fibrous scaffolds are capable of restoring the microarchitecture of the extracellular matrix (ECM). The current chapter focuses on some of the fabrication techniques which include coaxial, emulsion & co-electrospinning, edge electrospinning, gap electrospinning, 3D jet writing, and caged collector electrospinning & moving spinneret. Further, the application of multiscale fibrous scaffolds with respect to bone, cartilage, cardiovascular, liver, neural, skin and tendon tissue engineering has been discussed. [ABSTRACT FROM AUTHOR]

On the other hand, Giannaccare et al. [[192]] conducted a study on patients with MGD having subjective symptoms (OSDI>= 13) and at least one clinical sign of MGD, such as terminal ductal obstruction, plugging of the meibomian glands, turbid secretions, inflammation and swelling of the eyelid margins, or poor meibum secretions. One RCT [[423]] and two observational studies [[429]] assessed improvements in meibomian gland orifices and surrounding findings and report that minocycline oral administration can improve meibomian gland orifices and surrounding findings in patients with MGD and meibomitis. Additionally, Ibrahim et al. [[279]] show that meibomian gland acinar density, shortest and longest acinar diameter, and inflammatory cell density were significantly associated with BUT, fluorescein staining score, Rose Bengal staining, decreased lipid expression from the meibomian gland orifices, meibomian gland dropout, and ocular surface tear evaporation rate. In 22 patients without atrophy of the meibomian gland, after treatment with the cleansing agent, meibography indicated significant improvements in the meibomian gland orifices/surrounding findings (eyelid margin vascularity), quality of meibum, and BUT. [Extracted from the article]

Purpose: Dry eye can cause an increased risk of ocular infection due to loss of corneal epithelial integrity and changes to tear film homeostasis. Polymeric nanofibers with unique physicochemical and biological properties have attracted a lot of attention due to the improved in vivo performance of their conventional ocular formulations. The purpose of this present exposition was to assess the in vitro and in vivo efficacy of gatifloxacin (GAF)-loaded polyacrylonitrile (PAN) nanofiber in dry eye conditions. Methods: The nanofibers were characterized for morphology, drug entrapment, swelling behavior, drug release, oxygen permeability, biodegradability, antimicrobial potential, and sterility. Draize test, in vivo antibacterial activity, corneal healing characteristics, and tear quality profiles were also used to determine in vivo safety and efficacy. Results: Experimental findings suggested that electrospinning at defined conditions (applied voltage of 18 kV, flow rate of 0.5 mL/h, and tip to collector distance of 10 cm) produced smooth and continuous nanofibers with an average diameter of 480 nm. High drug entrapment of 95% combined with swelling indices of around 180% increased the controlled drug delivery capability of the prepared formulation. A slow degradation rate of 3±0.75% ensured a long-term cumulative drug release of 90% within 16 days. The inhibition diameter of the optimized formulation was found to be 15 ± 0.31 mm for E. coli and 13 ± 0.26 mm for S. aureus. Furthermore, after 3 days in an experimental dry eye animal model, the drug-loaded nanofiber showed better antibacterial activity, corneal healing, and tear film stability than the commercial eye drop. Conclusion: Overall, the study concluded that the GAF-loaded PAN nanofiber has good application prospects in the treatment of dry eye due to its safety and controlled drug release profile. [ABSTRACT FROM AUTHOR]

Introduction: The symptoms associated with Sjögren's disease (Sjögren's) are well-documented from the physician's perspective. However, from the patient's perspective, there is limited information on symptoms and their impact on health-related quality of life (HRQoL). This study aimed to provide an expanded understanding of patients' experience of Sjögren's and how symptoms impact HRQoL using a novel multi-method social media listening (SML) approach. Methods: A total of 26,950 social media posts with relevant content on Sjögren's posted by social media users from the USA, Canada, Australia, UK, France, Germany, Italy, Spain and China were analysed using an artificial intelligence natural language processing tool to explore patient conversations. Symptoms by level of impact on patients were characterised based on 'commonness' and 'bothersomeness'. Applied concept association analysis was used to assess relationships between symptom domains and impact domains. A qualitative framework was applied to explore words and phrases patients use to describe symptoms and their impacts. Results: Five of the identified symptom domains were very impactful: Pain; Dry Mouth and Throat; Fatigue, Energy and Sleep; Emotional Balance; and Dry Eye. The symptom domains Pain and Dry Mouth and Throat were the most common, while those of Emotional Balance and Fatigue, Energy and Sleep were the most bothersome. Symptom domains most closely associated with four HRQoL impact domains were Fatigue, Energy and Sleep, Dry Mouth and Throat and Dry Eye with Daily Functioning; Fatigue, Energy and Sleep with Financial Health; Emotional Balance with Psychological Wellbeing and Gynaecological Issues with Social Wellbeing. Conclusion: The results of this SML study show that Sjögren's affects diverse aspects of patients' lives, with symptoms extending beyond dry eyes and mouth and impacting daily living and functioning. Because symptoms may affect patients differently, these results highlight the importance of measuring impact on HRQoL to assess patient outcomes and treatment options in routine clinical practice and clinical trials. [ABSTRACT FROM AUTHOR]

Meibomian gland dysfunction (MGD) is highly prevalent and is the leading cause of evaporative dry eye disease (DED). MGD is characterized by a reduction in meibum secretion and/or a change in meibum composition that results in the disruption of the tear film lipid layer and an increase in the tear film evaporation rate. Excessive evaporation causes tear film instability, desiccation, tear hyperosmolarity, inflammation, and apoptosis of ocular surface cells, resulting in a continuous cycle of DED. The primary treatment goal for DED associated with MGD is to restore the tear film lipid layer and decrease evaporation, thereby reducing ocular signs and symptoms. The management of MGD includes home care options (eyelid hygiene, warming eye masks, ocular lubricants) and office-based treatments (manual expression, microblepharoexfoliation, thermal pulsation, intense pulsed light, intraductal probing). Topical ophthalmic prescription medications attempt to alter various factors that may contribute to DED (e.g., inflammation, bacterial growth, inadequate tear production). In this review, clinical evidence regarding available treatments and emerging therapies from randomized studies in patients with DED associated with MGD is summarized. Although some treatment modalities have been evaluated specifically for DED patients with MGD, large-scale randomized controlled trials are needed to confirm efficacy and safety in this patient population. Currently, there are no approved prescription pharmacologic treatments specifically indicated for DED associated with MGD, and those medications approved for the treatment of DED do not target the key driver of the disease (i.e., excessive evaporation). NOV03 (perfluorohexyloctane; under review with the US Food and Drug Administration) is the most advanced emerging therapy for DED associated with MGD and has demonstrated statistically significant improvements in both signs and symptoms in randomized controlled trials. Development of novel pharmacotherapies will improve therapeutic options and allow for a more individualized approach for patients with DED associated with MGD. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors are the target of more than 30% of all FDA-approved drug therapies. Though the purinergic P2 receptors have been an attractive target for therapeutic intervention with successes such as the P2Y12 receptor antagonist, clopidogrel, P2Y2 receptor (P2Y2R) antagonism remains relatively unexplored as a therapeutic strategy. Due to a lack of selective antagonists to modify P2Y2R activity, studies using primarily genetic manipulation have revealed roles for P2Y2R in a multitude of diseases. These include inflammatory and autoimmune diseases, fibrotic diseases, renal diseases, cancer, and pathogenic infections. With the advent of AR-C118925, a selective and potent P2Y2R antagonist that became commercially available only a few years ago, new opportunities exist to gain a more robust understanding of P2Y2R function and assess therapeutic effects of P2Y2R antagonism. This review discusses the characteristics of P2Y2R that make it unique among P2 receptors, namely its involvement in five distinct signaling pathways including canonical Gαq protein signaling. We also discuss the effects of other P2Y2R antagonists and the pivotal development of AR-C118925. The remainder of this review concerns the mounting evidence implicating P2Y2Rs in disease pathogenesis, focusing on those studies that have evaluated AR-C118925 in pre-clinical disease models. [ABSTRACT FROM AUTHOR]

Organ-on-a-chip (OOC) is an emerging interdisciplinary technology that reconstitutes the structure, function, and physiology of human tissues as an alternative to conventional preclinical models for drug screening. Over the last decade, substantial progress has been made in mimicking tissue- and organ-level functions on chips through technical advances in biomaterials, stem cell engineering, microengineering, and microfluidic technologies. Structural and engineering constituents, as well as biological components, are critical factors to be considered to reconstitute the tissue function and microenvironment on chips. In this review, we highlight critical engineering technologies for reconstructing the tissue microarchitecture and dynamic spatiotemporal microenvironment in OOCs. We review the technological advances in the field of OOCs for a range of applications, including systemic analysis tools that can be integrated with OOCs, multiorgan-on-chips, and large-scale manufacturing. We then discuss the challenges and future directions for the development of advanced end-user-friendly OOC systems for a wide range of applications. [ABSTRACT FROM AUTHOR]

Purpose: To assess the tear film layers and Meibomian glands by a noninvasive ocular surface analyzer in patients with and without type 1 diabetes mellitus (T1DM). Methods: Eighty-eight participants were enrolled in this study: 44 patients with T1DM without diabetic retinopathy, and 44 patients as a control group, between 18 and 49 years old. Limbal and bulbar redness classification, lipid layer thickness (LLT), tear meniscus height (TMH), first and mean noninvasive tear break-up time (FNIBUT and MNIBUT, respectively), and Meibomian glands loss (MGL) were assessment through the ICP Ocular Surface Analyzer (OSA). Schirmer's I test (SIT), the fluorescein tear break-up time test (TFBUT), OSDI and SPEED questionnaires, and percentage of glycosylated hemoglobin (HbA1c) were also tested. Results: The T1DM group showed higher limbal and bulbar redness (p = 0.010) and lower LLT (p < 0.001), TMH (p < 0.001), FNIBUT (p < 0.001), MNIBUT (p < 0.001), SIT (p = 0.001), and TFBUT (p < 0.001) than the control group. A higher percentage of MGL was found in the T1DM group in the upper (p = 0.097) and lower (p < 0.001) eyelids. No significant differences were found in dry eye symptoms across the OSDI and SPEED questionnaires between the two groups. Conclusion: Patients with T1DM without signs of retinopathy showed involvement of the mucoaqueous and lipid layers of the tear film, as well as a higher percentage of MGL, using a noninvasive analyzer. Dry eye disease in people with T1DM cannot be ruled out by anamnesis and subjective symptom questionnaires alone; therefore, these patients should undergo regular anterior pole examinations. [ABSTRACT FROM AUTHOR]

The use of artificial intelligence (AI) in the diagnosis of dry eye disease (DED) remains limited due to the lack of standardized image formats and analysis models. To overcome these issues, we used the Smart Eye Camera (SEC), a video-recordable slit-lamp device, and collected videos of the anterior segment of the eye. This study aimed to evaluate the accuracy of the AI algorithm in estimating the tear film breakup time and apply this model for the diagnosis of DED according to the Asia Dry Eye Society (ADES) DED diagnostic criteria. Using the retrospectively corrected DED videos of 158 eyes from 79 patients, 22,172 frames were annotated by the DED specialist to label whether or not the frame had breakup. The AI algorithm was developed using the training dataset and machine learning. The DED criteria of the ADES was used to determine the diagnostic performance. The accuracy of tear film breakup time estimation was 0.789 (95% confidence interval (CI) 0.769–0.809), and the area under the receiver operating characteristic curve of this AI model was 0.877 (95% CI 0.861–0.893). The sensitivity and specificity of this AI model for the diagnosis of DED was 0.778 (95% CI 0.572–0.912) and 0.857 (95% CI 0.564–0.866), respectively. We successfully developed a novel AI-based diagnostic model for DED. Our diagnostic model has the potential to enable ophthalmology examination outside hospitals and clinics. [ABSTRACT FROM AUTHOR]

Background: To assess the impacts of prolonged protective face masks (PFM) wear on ocular surface symptoms among healthcare professionals (HCPs), and how these symptoms affected PFM wear. Methods: Thirty-question survey forms were distributed via social media platform to 396 HCPs (110 doctors, 164 nurses, and 122 health technicians) between September 8 and 30, 2021. Participants who could not be reached via social media were given a face-to-face questionnaire. Aside from sociodemographic data, the questionnaire inquired about PFM wear, PFM types, ocular surface symptoms, and how PFM wear has changed during the COVID-19 pandemic. Results: A total of 74.5% of HCPs reported wearing PFMs, mostly surgical ones (76.8%), for half a day at work but not at home, with redness (29.3%) being the most frequently encountered ocular surface symptom, followed by burning (15.7%), pain (14.1%), tingling (10.9%), and rash (6.6%). The presence of associated restrictions in conjunction with PFM-related ocular symptoms was more likely in dry and hot environments. There was no significant relationship between PFM type, PFM-wearing duration, and HCPs' daily activities (p > 0.05). Despite the lack of a significant relationship between PFM types and ocular surface symptoms (p > 0.05), there was a significant relationship between PFM-wearing duration and ocular pain (p < 0.05). Conclusions: PFM-related ocular surface symptoms can be alleviated by properly wearing PFMs, reducing wear time, and using long-acting topical lubricants. This could improve PFM wear compliance, prevent disease transmission, and ultimately help with COVID-19 protection. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate the efficacy and safety of LipiFlow® thermal pulsation treatment system compared with lid massage combined warm compress in Chinese patients with meibomian gland dysfunction (MGD). Methods: Patients (n = 100 eyes, 50 subjects) diagnosed with MGD were recruited for this prospective, randomized, 3-month clinical trial. In Lipiflow group, patients (n = 50 eyes) received a single LipiFlow® thermal pulsation system treatment. In warm compress group, patients (n = 50 eyes) underwent warm compress daily for two weeks after an initial manual lid massage. Patients' symptoms were evaluated using Standard Patient Evaluation for Eye Dryness (SPEED) questionnaire. Safety parameters included best-corrected visual acuity (BCVA), intraocular pressure (IOP) and objective parameters including meibomian glands yielding lipid secretion (MGYLS) number, meibomian glands secretion (MGS) score, lipid layer thickness (LLT), tear-film breakup time (TBUT), corneal fluorescein staining (CFS) were measured and presented from baseline and to 3 months post-treatment. Results: Baseline parameters in both groups were comparable (p > 0.05). SPEED score and TBUT improved in two groups from baseline to 3 months. MGYLS number, MGS score, LLT improved in LipiFlow group and these improvements were maintained with no significant regression at 3 months. CFS showed significant improvement in warm compress group at 1 month compared with LipiFlow group. Moreover, the correlation analysis indicated LLT was positively correlated with TBUT, MGS score, and MGYLS number. Conclusion: A single 12-min LipiFlow treatment is an effective therapy for MGD patients and can achieve improvements in symptoms alleviation and meibomian gland lipid secretion function lasting for at least 3 months. [ABSTRACT FROM AUTHOR]