Search Results (149)

Background: Chronic kidney disease (CKD) is characterized by persistent inflammation, metabolic dysregulation, and mineral and bone disorder (CKD-MBD), all of which may affect ocular tissues. While retinal manifestations of CKD have been increasingly investigated, data regarding clinical anterior segment modifications and their relationship with systemic biochemical parameters remain limited. Methods: We performed a cross-sectional study including 130 participants: 53 non-CKD subjects, 29 patients undergoing maintenance hemodialysis (HD), and 48 kidney transplant recipients (KTRs). All participants underwent comprehensive ophthalmic examination, including best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement using Goldmann applanation tonometry, Schirmer I test, tear break-up time (TBUT) and assessment of cataract and blepharitis prevalence. Serum creatinine estimated glomerular filtration rate (eGFR), calcium, phosphate, parathyroid hormone (PTH), magnesium, 25-hydroxyvitamin D, and Activin A were recorded. Associations between ocular and systemic parameters were evaluated using correlation and regression analyses. Results: TBUT, Schirmer I and IOP did not differ significantly among groups (all p > 0.05). After adjustment for age, sex, BMI and diabetes mellitus (DM), HD patients showed worse visual acuity than the non-CKD reference group, reflected by higher logMAR BCVA values (adjusted B = +0.128, p = 0.024). In KTRs, higher corrected calcium was independently associated with reduced tear film parameters, correlating with both shorter TBUT (B = −0.903, p = 0.037) and lower Schirmer I values (B = −5.947, p = 0.008). Circulating Activin A increased progressively from controls to KTR to HD patients (median 189.5 vs. 273.0 vs. 314.0 pg/mL, p < 0.001) but showed no independent association with any anterior segment parameter; it was instead associated with cumulative glucocorticoid exposure (B = +1.602, p = 0.024). Conclusions: In CKD, clinical anterior segment and ocular surface differences were largely explained by age, sex, and comorbidity rather than renal replacement modality, with visual acuity deficit persisting in HD after adjusting for these covariates. At the individual level, corrected calcium was the parameter most consistently associated with tear film parameters in KTRs, whereas elevated Activin A was not independently associated with ocular involvement and likely reflects systemic disease activity. Full article

Background/Objectives: Fibromyalgia (FM) is a multifactorial disorder characterized by chronic pain, fatigue, asthenia, and sleep disturbances. FM may have effects on the eyes, such as dry eye disease (DED) and retinal changes. The aim of this study is to evaluate these ocular changes in FM patients. Methods: It is a single-center prospective study. Forty-two female patients with FM (Group 1) and 37 healthy controls (Group 2) participated in the study. Study participants underwent screening tests for DED and the retinal nerve fiber layer (RNFL) thickness. Results: According to the Schirmer test, Group 1 had lower scores with a significant difference (8.2 ± 4.36 mm vs. 17.51 ± 2.41 mm). When the tear film breakup time (TBUT) test values were analyzed, there was a significant difference between groups; Group 1 had lower scores (4.95 ± 2.26 s vs. 9.86 ± 1.64 s). When the RNFL thickness values were analyzed by quadrants, our results in Group 1 FM patients were lower in the superior temporal quadrant (117.98 ± 13.98 µm vs. 124.35 ± 13.71 µm). Conclusions: These findings indicate that patients with fibromyalgia may have increased dry eye findings and localized RNFL thinning, suggesting that fibromyalgia may be associated with both anterior and posterior segment ocular alterations. However, these parameters should be interpreted as ocular manifestations rather than diagnostic markers. Further studies are needed to determine their clinical relevance and potential biomarker value. Full article

Background/Objectives: Metabolic syndrome (MetS) and dry eye disease (DED) share inflammatory mechanisms, yet few studies have examined objective tear function and serum inflammatory markers together in this population. The aim of this study was to compare tear function tests and a panel of systemic inflammatory indices between patients with MetS who did and did not have DED. Methods: This observational comparative study enrolled 104 adults with MetS (52 MetS-DED and 52 MetS-nonDED), with group-level comparability for age and sex. All participants underwent ophthalmologic evaluation, including the Ocular Surface Disease Index (OSDI), the Schirmer I test, and fluorescein tear break-up time (TBUT). DED was defined by a mean Schirmer I value of ≤5 mm/5 min. Routine blood tests were used to derive the neutrophil-, platelet-, monocyte-, and eosinophil-to-lymphocyte ratios (NLR, PLR, MLR, ELR), the neutrophil–lymphocyte–platelet ratio (NLPR), the C-reactive protein (CRP)-to-albumin ratio, and the monocyte-to-high density lipoprotein cholesterol (HDL) ratio. Between-group comparisons, receiver operating characteristic (ROC) analysis with Youden’s index, and age- and sex-adjusted binary logistic regression were performed. Results: TBUT and Schirmer I values were significantly lower in the MetS-DED group, whereas OSDI scores did not differ between the groups. NLR, MLR, NLPR, CRP, and the CRP-to-albumin ratio were significantly higher in MetS-DED patients (all p < 0.05), while classic metabolic parameters were comparable. ROC analysis revealed statistically significant but weak-to-modest discriminatory ability (areas under the curve (AUCs) 0.617–0.652). In age- and sex-adjusted models, MLR (odds ratio (OR) = 1.072 per 0.01 unit, p = 0.046), the CRP-to-albumin ratio (OR = 1.062 per 0.01 unit, p = 0.011), and NLPR (OR = 1.123 per 0.001 unit, p = 0.038) remained significantly associated with MetS-DED. Conclusions: Among individuals with MetS, the presence of DED was accompanied by impaired tear function and a more pronounced systemic inflammatory profile despite similar metabolic parameters. However, the modest discriminatory performance and borderline adjusted associations indicate that these findings should be regarded as preliminary signals rather than evidence supporting the clinical use of these markers for screening or risk identification. Full article

Background: Dry Eye Disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability and inflammation. Cyclosporine A, an immunomodulator, and Diquafosol sodium, a mucin secretagogue, represent two distinct therapeutic pathways. However, current evidence directly comparing their clinical efficacy is inconsistent. This meta-analysis aimed to compare treatment outcomes and efficacy between 0.05% Cyclosporine A and 3% Diquafosol sodium in patients with moderate-to-severe DED. Methods: In January 2026, we conducted a systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library for randomized controlled trials directly comparing 0.05% Cyclosporine A to 3% Diquafosol sodium in adult patients with moderate-to-severe DED. For the meta-analysis, we used R 4.5.0 with R Studio 2024.12.1+563. Results: We included six RCTs with a total of 859 patients. No significant differences were found between Cyclosporine A and Diquafosol sodium in Tear Break-Up Time (TBUT) at 4, 8, or 12 weeks. Cyclosporine A showed a suggestive greater improvement in Schirmer test scores at 4 weeks (SMD = 0.35, 95% CI 0.07 to 0.63). A modest benefit in symptom scores favoring Diquafosol sodium was observed at 12 weeks (SMD = 0.23, 95% CI 0.06 to 0.41). Subgroup analysis suggested this symptomatic benefit may be more pronounced in patients with severe disease, although subgroup interaction tests were not statistically significant. There were no significant differences in corneal or conjunctival staining at any time point. The risk of adverse events did not differ significantly between treatments. Conclusions: Early improvement in tear production showed a potential benefit for Cyclosporine A, while longer-term symptomatic relief showed a potential benefit for Diquafosol sodium, with suggestive evidence in severe disease. However, these findings should be interpreted cautiously, given the methodological limitations and inconclusive TSA evidence for several outcomes. Future large-scale, standardized trials with extended follow-up are warranted to confirm these findings. Full article

Purpose: To evaluate the clinical efficacy and safety of eye drops containing lyophilized amniotic membrane (AM) in the treatment of dry eye disease (DED), with a focus on tear film stabilization and epithelial–immune balance. Methods: In this prospective cohort study, 40 patients (80 eyes) with DED were followed over six visits. The primary outcome was tear break-up time (TBUT). Secondary outcomes included corneal and conjunctival staining graded by the Oxford scale, meibomian gland parameters, corneal sensitivity (Cochet–Bonnet esthesiometry), best-corrected visual acuity, intraocular pressure (IOP), and Schirmer I test. Continuous variables were analyzed using repeated-measures ANOVA with Greenhouse–Geisser correction and Bonferroni post hoc testing; ordinal outcomes were analyzed using the Friedman test with Dunn–Bonferroni correction. Results: TBUT increased significantly in both eyes (OD: +5.3 s; OS: +4.9 s; both p < 0.001; ηp² ≈ 0.33). Corneal and conjunctival staining scores decreased (p < 0.001), meibomian gland quality and expressibility improved (p < 0.001), and corneal sensitivity increased (p < 0.001), while visual acuity and IOP remained stable. Schirmer I values showed no significant change. The combined pattern of changes (TBUT ↑, staining ↓, meibum/expressibility ↑, sensitivity ↑) indicates tear film stabilization and ocular surface improvement with a preserved safety profile. Conclusions: Lyophilized AM eye drops significantly prolong TBUT and improve clinical signs of DED, presumably by restoring the extracellular matrix (ECM) niche and the heavy-chain hyaluronan/pentraxin 3 (HC-HA/PTX3) complex, reducing proteolytic burden, and promoting a pro-resolving immune balance, with potential neurotrophic effects. These findings support the adjunctive use of AM-derived eye drops within contemporary TFOS DEWS II-based management algorithms for dry eye disease. Full article

Background/Objectives: To explore potential dry eye-related ocular surface functional alterations in women at the time of first diagnosis of endometriosis or adenomyosis in a real-world clinical setting. Methods: This was a cross-sectional case–control study. Patients were evaluated at the time of initial diagnosis, prior to initiation of any hormonal therapy, to reflect real-world clinical conditions. Participants underwent a standardized ocular surface assessment comprising the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer test, and multimodal TearCheck^® analysis, including Non-Invasive Break-Up Time (NIBUT), Tear Film Stability Evaluation (TFSE), Meibography, and Abortive Blinking^®. Results: A total of 71 women were included: 41 with endometriosis or adenomyosis and 30 without known gynecological disease. Patients reported significantly higher OSDI scores than controls (p < 0.05). Objective testing demonstrated lower Schirmer values, reduced tear film stability, and more pronounced Meibomian gland dropout in the patient group (all p < 0.05). Differences were consistently observed across both subjective and objective parameters. Conclusions: Women with endometriosis and/or adenomyosis exhibited significantly altered ocular surface parameters compared with women without known gynecological disease. These findings suggest a possible association between gynecological disease and ocular surface dysfunction. Greater awareness of potential ocular involvement may encourage closer collaboration between gynecology and ophthalmology in the care of affected patients. Full article

Background: Dry eye disease (DED) is a multifactorial disease. Numerous risk factors might cause DED, including indoor air pollution, such as incense. Incense (Bakhoor) is widely used in many cultures, including Saudi Arabia, although its smoke contains toxic chemicals that pose serious health hazards. This research investigates the link between the Schirmer II test and tear fluid proteins in DED patients. The study focuses on identifying the ocular examinations, hypothesizing that incense smoke, particularly from synthetic types, exacerbates DED. Methods: This pilot cross-sectional study was conducted at King Abdulaziz Medical City (KAMC) in Jeddah, Saudi Arabia. Participants were recruited from the Cornea and Ophthalmology Clinics. Eye assessments analyzed tear protein concentrations, including tear collection using Schirmer II test strips and tear break-up time (TBUT). The study included DED patients who used incense. Tear fluid from the Schirmer test of 20 randomly selected patients was used for protein analysis of total protein, lactoferrin, and Immunoglobulin E. Inclusion criteria were male and female subjects aged 18 years or older, diagnosed with DED, and using incense. The sample size was 55 participants, selected via convenience sampling. Subjective data were collected through questionnaires, as well as objective data from the tear test and the sample and analyzed with SPSS. Descriptive and inferential statistics were used, with statistical significance set at p-value < 0.05. Results: The Ocular Comfort Index (OCI) categories showed that 21.8% had no symptoms, 40.0% had low symptoms, 30.9% had moderate symptoms, and 7.3% reported high symptoms. TBUT values and Schirmer test scores decreased with increasing OCI severity, with no statistical significance. The mean (SD) of total protein in the right and left eyes for high OCI was 7.19 (1.39) and 7.42 (0.91), respectively, with no statistical significance. The immunoglobulin E levels in the right and left eyes for high OCI were 301.71 (55.97) and 301.71 (47.14), respectively, with no statistical significance. The mean (SD) of lactoferrin in the right and left eyes for high OCI was 163.77 (10.42) and 159.43 (1.68), respectively, with no statistical significance. Conclusions: The study findings demonstrate alignment in incense-using patients between subjective OCI symptom scores and objective clinical diagnostic measures. Specifically, higher OCI scores are associated with lower TBUT and Schirmer II test values, as well as changes in tear biomarkers such as IgE and lactoferrin. These findings emphasize the potential of using simple screening methods combined with bioanalytical markers for early detection of ocular surface disease. This highlights the potential health risks associated with incense exposure, particularly for individuals predisposed to DED. The urgency for further research to explore the long-term effects of incense on ocular health and to raise awareness about its potential impact on populations with high incense usage cannot be overstated. Full article

Background/Objectives: This study aimed to evaluate the relationship between cumulative occupational exposure and ocular surface alterations in Colombian tomato farm workers, using data collected through a cross-sectional survey. In addition, the study sought to explore how occupational exposure duration may support risk stratification and targeted preventive strategies in this vulnerable population. Methods: A cross-sectional observational study was conducted involving 72 tomato farm workers in Colombia. Participants were grouped according to duration of agricultural work experience (<15 years vs. ≥15 years). Clinical assessments included slit lamp examination, tear film break-up time (BUT), Schirmer test, and fluorescein staining. Subjective symptoms were evaluated using the McMonnies Dry Eye Questionnaire. Ocular surface alterations, including conjunctival changes and Meibomian gland dysfunction, were documented and statistically analyzed between groups. Results: Workers with ≥15 years of experience reported significantly higher dry eye symptom scores (McMonnies mean = 8.19 ± 2.54) than those with <15 years (mean = 6.59 ± 2.61; p = 0.006). Schirmer test scores were lower in the experienced group (16.30 ± 11.48 mm vs. 22.71 ± 11.20 mm; p = 0.018), indicating reduced tear production. Bulbar conjunctival alterations and Meibomian gland obstruction were significantly more frequent in the experienced group (p = 0.002 and p = 0.013, respectively). No significant differences were found in BUT or eyelid findings. Conclusions: Long-term agricultural work was associated with increased dry eye-related symptoms and clinical signs of ocular surface compromise among Colombian tomato farm workers. From a personalized medicine perspective, occupational exposure duration may represent a useful risk-stratification factor to identify workers who could benefit from targeted screening, preventive counseling, protective interventions, and individualized follow-up. These findings support the implementation of tailored occupational eye health strategies to reduce cumulative ocular surface damage in vulnerable rural populations. Full article

Background/Objectives: Lipid layer thickness (LLT) is widely used to assess tear film status in dry eye disease (DED), but single-point measurements may not adequately reflect spatial lipid distribution driven by tear film dynamics. This study evaluated whether the combined assessment of inferior and superior corneal LLT provides additional clinical relevance for interpreting DED subtypes. Methods: This cross-sectional study included 614 eyes of 614 patients with DED. Inferior corneal LLT (LLT_inf) was measured using a tear interferometer, and superior corneal LLT (LLT_sup) was graded using an LED-based slit-lamp assessment. DED parameters, including meibomian gland expressibility (MGE), meibum quality, tear meniscus height, Schirmer I test, and fluorescein tear break-up patterns, were analyzed. Results: Low LLT_inf showed worse meibomian gland function, with higher MGE scores than in the high LLT_inf group (1.9 ± 0.8 vs. 1.2 ± 0.9, p < 0.001). Higher LLT_inf was associated with lower aqueous parameters, and aqueous deficiency was observed in 57.4% of the high LLT_inf group increasing to 83.0% when LLT_sup was low. Combined LLT_inf–LLT_sup assessment improved the prediction of aqueous deficiency compared with LLT_inf alone (AUC, 0.719 vs. 0.559). Improvement for moderate-to-severe MGD was smaller (AUC 0.731 vs. 0.653). Conclusions: LLT reflects not only lipid secretion, but also aqueous-driven distribution. The combined assessment of LLT_inf and LLT_sup may improve the interpretation of LLT findings and provide additional insight into tear film dynamics in DED. However, its predictive performance remains moderate, suggesting that this approach is considered a complementary interpretive framework rather than a standalone diagnostic tool. Full article

Background: To evaluate the effects of a preservative-free artificial tear formulation containing trehalose, sodium hyaluronate, and N-acetyl-aspartyl-glutamate (NAAGA) on ocular surface parameters and quality of life in patients with primary open-angle glaucoma (POAG) treated with preserved versus preservative-free prostaglandin analogues. Methods: For this prospective, observational clinical study, thirty-eight patients (76 eyes) with POAG receiving stable topical prostaglandin therapy were enrolled and divided into two groups: preserved prostaglandins (Group 1, n = 44) and preservative-free prostaglandins (Group 2, n = 32). All patients received adjunctive preservative-free artificial tears (trehalose, sodium hyaluronate, NAAGA) three times daily for one month. Assessments at baseline (T0) and 1 month (T1) included best-corrected visual acuity (BCVA), intraocular pressure (IOP), contrast sensitivity, Schirmer test, tear break-up time (BUT), Efron grading scale, Ocular Surface Disease Index (OSDI), visual field (VF) indices (Mean Deviation (MD), Pattern Standard Deviation (PSD), Visual Field Index (VFI)), and quality of life (QoL) measured using Visual Analogue Scales (VAS). Results: After 1 month, both groups demonstrated significant improvement in ocular surface parameters. Schirmer test increased by approximately 4–5 mm (p = 0.001 in both groups), and BUT improved by 5 s (p = 0.001 in both groups). OSDI scores significantly decreased (Group 1: –18.5; Group 2: –23; p = 0.001 for both), and Efron grading significantly improved (p = 0.001 in both groups). Artificial tears-related QoL markedly increased in both groups (p = 0.001), while pathology-related QoL remained unchanged. IOP showed a modest but significant reduction in both groups (Group 1 p = 0.011; Group 2 p = 0.003), without intergroup differences. VFI significantly improved in both groups from T0 to T1 (Group 1 p = 0.013; Group 2 p = 0.04). Group 1 also showed an improvement in terms of PSD (p = 0.025). Conclusions: Adjunctive treatment with preservative-free artificial tears containing trehalose, sodium hyaluronate, and NAAGA significantly improved tear film stability VF indexes, ocular surface signs and symptoms, and patient-reported QoL in POAG patients treated with prostaglandins, regardless of preservative status. Routine ocular surface optimization should be considered an integral component of comprehensive glaucoma management. Full article

Background/Objectives: To evaluate the relationships between meibomian gland dysfunction (MGD), ocular surface parameters, and matrix metalloproteinase-9 (MMP-9)-mediated inflammation in glaucoma patients, we specifically assessed the impact of prostaglandin analogue use, preservative exposure, and number of medications. Methods: This retrospective cross-sectional study included patients treated with topical antiglaucoma medications for at least six months. Meibomian gland expressibility, meibum quality, and MGD grade were assessed along with tear film break-up time (TBUT), Schirmer I test, and Oxford staining score. Tear MMP-9 levels were measured using a Point-of-Care immunoassay (InflammaDry^®) and graded on a 0 to 4 scale. Results: Elevated MMP-9 grades were significantly correlated with worsening meibum expressibility, meibum quality, and MGD grade (all p < 0.001), whereas no significant associations were found with traditional parameters such as TBUT and Schirmer I test. Prostaglandin analogue use was associated with worse meibomian gland parameters and higher MMP-9 levels compared to non-use. Patients receiving preservative-containing medications exhibited poorer meibomian gland parameters and MMP-9 levels, as well as worse corneal staining scores. An increased number of medications was associated with a stepwise deterioration in meibomian gland function and elevated MMP-9 levels. Conclusions: Prostaglandin analogue use, preservative exposure, and increased number of medications are significant factors associated with the exacerbation of MGD and ocular surface inflammation. Semi-quantitative grading of tear MMP-9 revealed a stepwise association with meibomian gland dysfunction severity that was not detected by conventional dry eye metrics, indicating that MMP-9 may be considered a potential indicator of subclinical ocular surface inflammation in glaucoma patients. Full article

Dry eye disease (DED) is a complex, multifactorial, progressive disease that has consequences both for individuals and society. Symptoms reported by patients include discomfort in the eye and periodic blurred vision, while in the broader perspective, the disease is associated with economic burdens and challenges for healthcare systems. Globally, dry eye disease remains a growing problem observed in many countries. It is estimated that symptoms of dry eye syndrome occur in approximately 10 to 20 per cent of people over the age of 40. This prevalence is on the rise, which is associated with both the aging population and increased incidence among younger adults. In this group, factors such as contact lens wear and prolonged use of digital devices are considered to be contributing factors. Further epidemiological studies, conducted in different regions of the world, covering diverse populations and a wide range of age groups, with a particular focus on younger cohorts, may contribute to a more accurate understanding of the prevalence of dry eye disease. There are more and more methods of diagnosing DED. In addition to well-known procedures like the Schirmer test or tear break-up time, there are also methods that focus on the evaluation of the tear film or imaging of the ocular surface. Moreover, usage of artificial intelligence is also playing a significant role in it. However, the key issue in individual cases is introducing the most effective treatment based on combining available substances, including corticosteroids, antibiotics and supplements, which leads to a reduction in inflammation and improvement in visual comfort. Full article

Feline conjunctivitis is a common ocular disorder; however, the molecular composition of feline tear fluid and its alterations during ocular surface inflammation remain poorly characterized. This pilot study aimed to explore the tear proteome of cats with conjunctivitis using matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI–TOF/TOF MS) and to compare findings with those from clinically healthy cats. Tear samples were collected using Schirmer tear test strips from healthy cats and cats diagnosed with conjunctivitis. Total protein concentration was measured by ultraviolet absorbance spectrophotometry, and tear proteins were separated by SDS–polyacrylamide gel electrophoresis, followed by in-gel trypsin digestion and MALDI–TOF/TOF MS analysis. Nine distinct tear proteins were identified, including antimicrobial and immune-related components such as lactoperoxidase, lactotransferrin, albumin, and immunoglobulin A constant region. Lactoperoxidase and SBP1 were identified in feline tear fluid for the first time. No proteins uniquely associated with conjunctivitis were detected. The mean total tear protein concentration was numerically higher in cats with conjunctivitis (13.06 ± 0.75 mg/mL) than in healthy cats (9.69 ± 0.67 mg/mL); however, this difference did not reach statistical significance (p = 0.095) and should be interpreted cautiously given the limited sample size. This pilot study provides preliminary insights into tear protein profiles in cats with conjunctivitis and highlights the need for larger quantitative investigations. These findings provide a preliminary framework for future studies aimed at further characterizing molecular alterations associated with feline ocular surface disorders. Full article

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

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR–EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41–75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose–response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit. Full article