Dry Eye Symptoms Research Articles

Sjogren's syndrome due to immune checkpoint inhibitors (ICIs): Insights from a single-institution series and systematic review of the literature.

Careful adverse event assessment and management are important when prescribing immune checkpoint inhibitors (ICIs) to cancer patients. Iatrogenic Sjogren's syndrome is a relatively rare immune-related adverse event (irAEs) that affects the moisture-producing glands. We describe a series of four patients who developed Sjogren's syndrome while being treated with ICIs at a community cancer center in Southern California, USA (1/1/2017-12/31/2023). Patient, drug and disease-related data were collected by retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases in the literature (1/1/2016-12/31//2023). Of 224 cancer patients at our center treated with ICIs, four (1.8%) developed iatrogenic Sjogren's syndrome. All of our patients were male; three received PD-1 inhibitors (nivolumab, pembrolizumab) and one received the PD-L1 inhibitor atezolizumab. The median time to development of Sjogren's syndrome was 24 weeks (range, 8-36 weeks); dry mouth symptoms were more prominent than dry eye symptoms. None of the patients had elevated SS-A, SS-B or antinuclear antibodies. One patient developed multiple tooth cavities and had several extractions, due to severe xerostomia. Management of all patients was primarily symptomatic. Two cases were irreversible; one was reversible and the 4th case is undermined as he is still on ICI therapy. Our systematic review of the literature identified 80 cases in five articles. Incidence of xerostomia was twice of that of xerophthalmia. The male/female ratio was 1.5:1. SS-A, SS-B, or antinuclear antibodies were found in only 9% of patients. Steroids were reported to have had only a limited role in management. The incidence of Sjogren's syndrome due to ICIs in our center was 1.8%. Details of clinical course and management in these patients are presented. Caring for patients with ICI-related Sjogren's syndrome is facilitated by a multidisciplinary effort including oncologists, otolaryngologists, dentists, ophthalmologists and rheumatologists. Expanding the knowledge base pertaining to iatrogenic Sjogren's syndrome in patients on ICIs will be helpful in promoting early detection and treatment, and improving outcomes.

Effect of low-level light therapy in individuals with dry eye disease.

Low-level light therapy (LLLT) or photobiomodulation, the application of red light to the eye, is used for the treatment of dry eye. Limited studies have investigated the efficacy of LLLT as a stand-alone treatment. The investigation aimed to evaluate the effect of LLLT on signs and symptoms of dry eye. Participants with mild to moderate dry eye were recruited for this three-visit study. Visits were 7 (±3) days apart and all participants received 633 nm LLLT (eye-light®) for 15 min at each visit. Clinical measures including first and average non-invasive keratograph tear break-up time (NIKBUT), tear meniscus height (TMH), meibomian gland (MG) loss for upper and lower eyelids, ocular surface disease index (OSDI) score, tear film lipid layer thickness, meibum quality score, Schirmer's test, corneal fluorescein staining and eyelid temperature for external upper (EUL) and external lower (ELL) eyelids were measured from the right eye of participants before and after treatment. Thirty participants (mean [SD] age: 31.1 [9.5] years) completed the study. Treatment with LLLT resulted in significant differences in first and average NIKBUT, TMH, tear film lipid layer thickness, OSDI score, Schirmer's test, meibum quality score and eyelid temperature over time (all p < 0.05). Compared to baseline, TMH, tear film lipid layer thickness and eyelid temperature significantly increased by 0.06 mm (95% CI: 0.01-0.11), 12.9 nm (95% CI: 1.18-24.55), and 7.0°C, respectively,for both EUL (95% CI: 6.17-7.84) and ELL (95% CI: 6.17-7.73). The respective decrease in the OSDI score and Schirmer's test was 10.2 (95% CI: -15.15 to -5.26) and 4.4 mm (95% CI: -7.31 to -1.42; all p < 0.05). There was no significant difference in corneal fluorescein staining and MG loss after LLLT. Low-level light therapy treatment significantly improved signs and symptoms of dry eye in the early phases of treatment, suggesting its efficacy for dry eye management.

Effect of the use of biological therapy on dry eye parameters in patients with Sjögren’s syndrome

Abstract Purpose: To compare dry eye symptoms and signs in a group of patients with Sjögren’s syndrome (SS), before and after the start of biological therapy for active systemic disease. Methods: Observational longitudinal retrospective study, including adult patients with a previous diagnosis of primary or secondary SS. Ocular Surface Disease Index (OSDI) test, tear breakup time (TBUT), and Schirmer test where registered before and after at least 1 year of use of biological therapy. Results: One hundred and nineteen patients were included, 83 (69.7%) females and 36 (30.3%) males, average age was 62.2 years, and the average time of use of biologics was 3.6 years. The main biologic agents used were adalimumab (22.7%), infliximab (20.2%), rituximab (16.0%), etanercept (13.4%), and abatacept (7.6%). After the implementation of biologic therapy, the percentage of patients with deficient and severely deficient Schirmer’s test decreased from 64.7% to 60.5% and from 18.5% to 11.8%, respectively, whereas adequate test increased from 16.8% to 27.7%. Deficient TBUT decreased from 74.8% to 63.0%. In OSDI evaluation, the percentage of asymptomatic patients increased from 3.4% to 18.5%, and severe symptoms decreased from 26.9% to 9.2%. Individual therapy analysis failed to find significative changes in terms of percentage variation and Cohen’s kappa for objective variables; however, substantial changes were observed in the OSDI test, particularly in patients treated with infliximab, rituximab, and abatacept. Conclusion: Use of biologics in SS remains restricted to patients with systemic active disease; however, a possible effect on dry eye symptoms arises as a secondary outcome, which could positively impact quality of life.

Effectiveness of 0.3% Hyaluronic Acid Eye Drops for Benign Essential Blepharospasm and Hemifacial Spasm with Botulinum Toxin-induced Dry Eye.

This study evaluates the effectiveness of 0.3% hyaluronic acid (HA) eye drops in patients receiving concurrent botulinum toxin (BoNT) injections for benign essential blepharospasm (BEB) or hemifacial spasm (HFS). This randomized controlled cross-over trial study involved 14 patients with BEB and 33 patients with HFS randomized into two groups (early treatment and deferred treatment) for 3 months of treatment with 0.3% HA eye drops. Data collected at baseline, 3 months, and 6 months included Blepharospasm Severity Scale (BSS) score in patients with BEB; Samsung Medical Class Grading Scale score in patients with HFS; and dry eye symptoms, lower eyelid tear meniscus height (TMH), tear breakup time (TBUT), and corneal fluorescein staining in both groups. After 3 months of 0.3% HA instillation, patients with BEB in both groups showed significant improvement in BSS, TMH, TBUT, and the amelioration of subjective dry eye symptoms and corneal staining (P < 0.05). However, discontinuation of 0.3% HA eye drops worsened BSS, TMH, and TBUT. Patients with HFS also experienced significant improvement in Samsung Medical Class score, subjective dry eye symptoms, and objective corneal findings (P < 0.05). Treatment with 0.3% HA eye drops led to significant improvement in spasm severity, and dry eye parameters, after 3 months of instillation in patients with BEB or HFS during concurrent treatment with BoNT injections. The 0.3% HA eye drops were safe and might serve as an add-on treatment for symptom improvement.

Effects and Safety of 5% Lifitegrast Ophthalmic Solution in Patients With Dry Eye Disease Associated With Ocular Graft-Versus-Host Disease.

Introduction Graft-versus-host disease (GVHD) is a common sequela of hematopoietic stem cell transplant (HSCT). While HSCT is often curative for certain hematologic malignancies, acute and chronic GVHD remains an important cause of morbidity and mortality in post-transplant patients. Ocular involvement is one manifestation of chronic GVHD that can present similarly to chronic dry eye with tear film abnormalities, aqueous deficiency, and corneal epithelial defects through melting and perforation. Current management includes frequent use of artificial tears and oral or topical glucocorticoids as tolerated. There is a need for long-term, steroid-sparing therapeutics in the management of ocular GVHD (oGVHD). Lifitegrast is approved for the treatment of chronic dry eye and may have therapeutic potential in the treatment of oGVHD. The aim of this study was to investigate the efficacy and safety of topical lifitegrast in the management of oGVHD. Methodology A prospective randomized clinical trial (NCT04792580) was performed on 32 enrolled patients with diagnosed oGVHD. Subjects underwent a two-week washout period consisting of preservative-free artificial tears dosed twice a day, after which they were randomized to the treatment arm (5% lifitegrast ophthalmic solution) or placebo arm (vehicle solution) for four weeks. Endpoints included Symptom Assessment iN Dry Eye (SANDE) score, unanesthetized Schirmer score, Ocular Surface Disease Index questionnaire score, fluorescein staining, tear film breakup time, meibum quantity, and turbidity. Safety endpoints included intraocular pressure, visual acuity, and rate of treatment-related adverse effects. Statistical analysis was done with a t-test or Wilcoxon rank-sum test. Results The primary and secondary efficacy endpoints were met, with statistically significant reductions in mean SANDEand unanesthetized Schirmer score observed at four weeks post-randomization. No serious adverse events related to the use of either lifitegrast or vehicle were observed, and no worsening of visual acuity or intraocular pressure occurred in the intention-to-treat analysis. However, further inference was limited due to insufficient statistical power owing to significant washout and a 50% dropout rate from the all-enrolled analysis set. The most common causes of study dropout were worsening of unrelated medical conditions (not GVHD) and improvement of SANDE score or Schirmer score outside of the inclusion criteria range during the washout period. Conclusions Lifitegrast may be a useful steroid-sparing agent in the long-term management of oGVHD. This study provides further support for the clinical evidence of lifitegrast in the management of dry eye signs and symptoms, although further sufficiently powered clinical trials are warranted to better understand its efficacy in the oGVHD population. Personalized treatment options targeting distinct manifestations of oGVHD in the cornea, tear film, lid margin, and conjunctiva are needed in the effective management of this multifaceted and complex disease.

Prevalence of symptomatic dry eye disease (DED) among a population of contact lens wearers in Jordan

Prevalence of symptomatic dry eye disease (DED) among a population of contact lens wearers in Jordan

Dry eye disease as an occupational risk factor in operating room nurses

ABSTRACT Clinical relevance Knowing occupational risks in a multifactorial disease such as dry eye disease is important for disease diagnosis and treatment. Background Dry eye disease (DED) is a multifactorial disease of the ocular surface characterised by tear film instability, adversely affecting visual function and quality of life. The operating room environment has many risk factors for DED such as air conditioning, constant humidity, constant room temperature, intense lighting, surgical smoke, anaesthetic gases and irritating chemicals, and prolonged mask use. This study investigates the ocular surface findings and blink patterns of operating room nurses at risk of DED. Methods A total of 68 nurses (operating room, n = 34; outpatient clinic, n = 34) were included in this study. The diagnosis of DED was assessed using a questionnaire, best-corrected visual acuity, tear break-up time, corneal fluorescein staining, meibomian gland assessment, Schirmer I test. All the tests were conducted in the same area. Results According to the ocular surface disease index, the rate of dry eye symptoms was significantly higher among operating room nurses than among outpatient nurses (70.5% vs 41.1%). Severe dry eye symptoms were more common in the operating room group. The meibomian gland score was higher in the operating room group (29.4% vs 5.9%). The numbers of blinks (30.91 ± 12.81 vs 21.05 ± 7.77) and incomplete blinks (8.76 ± 4.68 vs 5.76 ± 3.20) at rest were higher in operating room nurses. Conclusion The occupational risk for DED was high among operating room staff. National and international standards for the prevention and management of DED in personnel involved in health care services are needed.

The Near‐Infrared Light Emitted by LiScO2:Cr3+ Phosphor Used to Induce Gland Secretion for Sjogren's Syndrome

AbstractPhotobiomodulation is promisingly used as a noninvasive new weapon against Sjogren's syndrome, which is a disorder of immune system with two main symptoms of dry eyes and a dry mouth. This work reports a new NIR LED device made from LiScO2:Cr3+ phosphor for the application. The absorbance, internal, and external quantum efficiency of the optimal Li(Sc0.98Cr0.02)O2 phosphor reach 40.9%, 34.5%, and 14.1%, respectively; and the output power and energy conversion efficiency of the LED device packaged using the phosphor driven under 20 mA are 4.23 mW, respectively. The emission spectrum of the LED device can well cover the action spectrum of oxidized CuA in cytochrome c oxidase molecules. Both the pathological changes of mice submandibular gland and the expression of human submandibular gland epithelial cells (HSG) in AQP5, M3R andEGR1 confirm that the NIR light has great potential application for treating Sjogren's syndrome. Moreover, study with mice approved that the therapy using the NIR light is more efficient than the conventional medicine treatment using hydroxychloroquine sulfate.

Comparing signs and symptoms of dry eye treated with organic versus conventional lubricant eye drops

Purpose: This study aimed to investigate and compare changes in symptoms, signs, and clinical tests between two different lubricant eye drop treatments in patients with dry eye secondary to Meibomian gland dysfunction (MGD). Methods: This prospective clinical study included 20 symptomatic patients with MGD-induced dry eye. Participants who were diagnosed with dry eye were treated with either a certified organic artificial tear (AT) (O group) or a non-organic AT (C group) for 4 weeks and re-evaluated. Both treatments consisted of the same active ingredient, glycerin. The findings from the first and second visit were assessed. Differences between the effect of each treatment on signs and symptoms were analyzed. Dry eye symptoms, subjective wellness, tear break-up time (TBUT), tear osmolarity, and lid margin assessment were the variables evaluated. Results: Both treatment groups demonstrated improvements in objective tests, symptoms, and wellness. A larger percentage of patients in the C group reported symptomatic improvement, which was greater than in the O group. The O group exhibited a higher average improvement in wellness as well as greater improvement in TBUT and tear osmolarity than the C group. Conclusion: Conventional and organic lubricant eye drops both achieved clinical improvements in the signs and symptoms of MGD-induced Evaporative dry eye (EDE). Organic eye drops demonstrated a greater effect on overall wellness, TBUT, and tear osmolarity.

Effect of Periodontitis on Dry Eye Disease Signs and Symptoms: A Cross-sectional Study.

Gingivitis and periodontitis are oral disorders characterised by chronic inflammation, impacting the supportive structures around teeth due to bacterial accumulation. While the role of inflammation in both periodontitis and dry eye disease (DED) has been established individually, their potential association remains unclear. This study aimed to investigate the association between periodontitis and the manifestation of signs and symptoms related to DED in patients aged 18-40. A cross-sectional study was conducted involving healthy controls, DED patients with or without periodontitis, and patients with periodontitis without DED. Ophthalmic and oral examinations were performed, and demographic, ocular, and systemic disease data were collected. Statistical analysis was conducted using ANOVA and chi-squared tests. A total of 684 participants were included in the study. Significant elevations in tear osmolarity levels, increased Ocular Surface Disease Index scores (OSDI), and decreased tear break-up time (TBUT) and Schirmer (ST-I) values were observed in DED patients with periodontitis compared to individuals with DED but without periodontitis, as well as control and periodontitis groups. Furthermore, higher neutrophil-to-lymphocyte ratios (NLR) were found in DED patients with periodontitis. The findings suggest an association between periodontitis and the severity of signs and symptoms related to DED. The study highlights the importance of interdisciplinary approaches in understanding the systemic implications of periodontal disease and its potential impact on ocular health.

Ocular surface in patients with different degrees of myopia.

To investigate the clinical features of the ocular surface in patients with different degrees of myopia. A cross-sectional study was conducted involving 122 participants with myopia in Beijing Tongren Hospital from February to June, 2023. After completing the Ocular Surface Disease Index (OSDI) score scale, measurements were taken for refraction, biometric parameters and ocular surface parameters. The prevalence, severity and related parameters of the dry eye among different groups based on axial length (AL) were compared. Correlation analysis was performed between ocular surface parameters and refraction/biometric measurement parameters. Statistically significant differences were observed in refractive error, corneal thickness, anterior chamber depth, and subfoveal choroidal thickness among the groups (all P<0.05). With the increase in AL, the incidence and severity of dry eye increased significantly (P<0.05). Moreover, the tear film break-up time (BUT) shortened (P<0.05), and the corneal fluorescein staining (CFS) points increased significantly (P<0.05). OSDI scores were positively correlated with AL and spherical equivalent (SE; both P<0.05); BUT was negatively correlated with AL, SE, and corneal astigmatism (AST; all P<0.05); Schirmer I test (SIT) results were negatively correlated with AL and SE (both P<0.05). AL elongation is a risk factor for dry eye onset in myopic participants. The longer the AL, the more severe the dry eye is, with the increased CFS spots and tear film instability. Additionally, SE and AST exhibit negative correlations with dry eye symptom scores and ocular surface parameters.

Recombinant human nerve growth factor (cenegermin) for moderate-to-severe dry eye: phase II, randomized, vehicle-controlled, dose-ranging trial

BackgroundDry eye disease (DED) includes neurosensory abnormalities as part of its multifactorial etiology. Nerve growth factor is important for maintaining corneal nerve integrity and wound healing. Cenegermin (recombinant human nerve growth factor) is a topical biologic that promotes corneal healing in patients with neurotrophic keratitis. The purpose of this study was to evaluate efficacy and safety of cenegermin in moderate-to-severe DED and identify an optimal dosing strategy.MethodsThis was a phase II, multicenter, randomized, double-masked, vehicle-controlled, dose-ranging clinical trial in patients with moderate-to-severe DED, including Sjögren’s DED (NCT03982368). Patients received 1 drop of cenegermin 3 times daily (t.i.d.; 20 mcg/mL), cenegermin 2 times daily (b.i.d.; 20 mcg/mL) and vehicle once daily, or vehicle t.i.d. for 4 weeks. Follow-up continued for 12 additional weeks. The primary endpoint was change in Schirmer I score from baseline to week 4. Other key endpoints included rate of responders (Schirmer I test > 10 mm/5 min) after treatment and change in Symptoms Assessment iN Dry Eye (SANDE) scores from baseline to end of follow-up. A 1-sided test (α = 0.025) was used to evaluate statistical significance.ResultsAt week 4, mean changes in Schirmer I scores were not statistically significantly different in either cenegermin group versus vehicle (cenegermin vs vehicle [treatment difference; 95% CI]: t.i.d., 2.60 mm and b.i.d., 3.99 mm vs 1.68 mm [t.i.d.: 0.93; −1.47 to 3.32, P = 0.078; b.i.d.: 2.31; −0.08 to 4.70, P = 0.066]). More patients responded to treatment with cenegermin t.i.d. and b.i.d. versus vehicle (t.i.d.: 25.9% [21/81, P = 0.028]; b.i.d.: 29.3% [24/82, P = 0.007] vs 11.9% [10/84]), with statistical significance (set at P < 0.025) observed in the b.i.d. group. Only cenegermin t.i.d. yielded statistically significant (P < 0.025) reductions in SANDE scores versus vehicle, which were sustained up to the end of follow-up (P value range, 0.002–0.008). Eye pain, primarily mild and transient, was the most frequently observed treatment-emergent adverse event with cenegermin. Similar results were observed in patients with Sjögren’s DED.ConclusionsCenegermin was well tolerated and although this study did not meet its primary endpoint, significant improvement in patient-reported symptoms of dry eye was observed through follow-up. Larger studies evaluating cenegermin in patients with DED are warranted.Trial registrationNCT03982368; registered May 23, 2019.

Reticulated Retinoic Acid Synthesis is Implicated in the Pathogenesis of Dry Eye in Aqp5 Deficiency Mice.

Abnormalities in aquaporins are implicated in the pathological progression of dry eye syndrome. Retinoic acid (RA) regulates cellular proliferation, differentiation, and apoptosis in the cornea, thereby being associated with dry eye disease (DED). The objective of this study is to explore the underlying mechanisms responsible for RA metabolic abnormalities in corneas lacking aquaporin 5 (AQP5). Dry eye (DE) models were induced via subcutaneous scopolamine hydrobromide. Aqp5 knockout (Aqp5-/-) mice and DE mice were utilized to assess corneal epithelial alterations. Tear secretion, goblet cell counts, and corneal punctate defects were evaluated. The impact of Aqp5 on RA-related enzymes and receptors was investigated using pharmacological RA or SR (A JunB inhibitor), a transcription factor JunB inhibitor, treatment in mouse corneal epithelial cells (CECs), or human corneal epithelial cells (HCECs). The HCECs and NaCl-treated HCECs underwent quantitative real-time PCR (qRT-PCR), immunofluorescent, Western blot, and TUNEL assays. The regulation of transcription factor JunB on Aldh1a1 was explored via ChIP-PCR. Aqp5 and Aldh1a1 were reduced in both CECs of DE mice and NaCl-induced HCECs. Aqp5-/- mice exhibited DE phenotype and reduced Aldh1a1. RA treatment reduced apoptosis, promoted proliferation, and improved the DE phenotype in Aqp5-/- mice. JunB enrichment in the Aldh1a1 promoter was identified by ChIP-PCR. SR significantly increased Aldh1a1 expression, Ki67, and ΔNp63-positive cells, and decreased TUNEL-positive cells in CECs and HCECs. Our findings demonstrated the downregulation of Aqp5 expression and aberrant RA metabolism in DE conditions. Knockout of Aqp5 resulted in reduced production of RA through activation of JunB, subsequently leading to the manifestation of DE symptoms.

Body mass index, diet, and outdoor activity linked with meibomian gland abnormalities in children.

Dry eye disease is frequently underdiagnosed in pediatric patients. Meibomian gland morphology abnormalities (atrophy and tortuosity) may be associated with dry eye. This study examined risk factors for gland morphology abnormalities in children. This study aimed to characterize meibomian gland morphological abnormalities (atrophy and tortuosity) and identify risk factors for the same in children. A total of 160 children, primarily African American and Hispanic, aged 5 to <18 years underwent a comprehensive eye exam including slit-lamp examination to evaluate the meibomian glands, conjunctival papillae, and tear film. Infrared photography was performed including assessment of noninvasive tear film breakup time and tear meniscus height. Meibomian gland atrophy and tortuosity were assessed. A modified Ocular Surface Disease Index survey was administered along with surveys on screen time, diet, and outdoor activity. Linear multiple regression was performed to determine risk factors for meibomian gland abnormalities. The average age of participants (76 male, 84 female) was 10.9 ± 3.0 years. Severe meibomian gland atrophy (score ≥2) was found in 31.0% of participants in at least one eyelid. Severe meibomian gland tortuosity (score ≥2) was found in 84.0% of participants in at least one eyelid. The median symptom score was 9.8 (range, 0 to 71), with 16.9, 8.8, and 12.5% of the children having mild, moderate, and severe dry eye symptoms, respectively. Elevated body mass index (p<0.001), reduced outdoor activity (p=0.02), and unhealthy diet (p=0.01) were found to be risk factors for meibomian gland abnormalities. Screen time, symptom score, age, gender, and race/ethnicity were not associated with gland abnormalities (all p values >0.05). This study determined that meibomian gland morphological abnormalities were commonly found in children aged 5 to <18 years. Risk factors for these abnormalities include elevated body mass index, an unhealthy diet, and reduced outdoor activity.

Case Series: Severe meibomian gland loss in polycystic ovarian syndrome patients on estrogen-progesterone therapy: A case series

Purpose: To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Methods: Case series. Results: Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Conclusions: Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.

Tear Fluid Progranulin as a Noninvasive Biomarker for the Monitoring of Corneal Innervation Changes in Patients With Type 2 Diabetes Mellitus.

This study aimed to investigate the expression levels of progranulin (PGRN) in the tears of patients with diabetic retinopathy (DR) versus healthy controls. Additionally, we sought to explore the correlation between PGRN levels and the severity of ocular surface complications in patients with diabetes. In this prospective, single-visit, cross-sectional study, patients with DR (n = 48) and age-matched healthy controls (n = 22) were included and underwent dry eye examinations. Tear fluid was collected, and its components were analyzed using the Luminex assay. The subbasal nerve plexus of all participants was evaluated by in vivo confocal microscopy. Patients with DR exhibited more severe dry eye symptoms, along with a reduction in nerve fiber density, length, and branch density within the subbasal nerve plexus, accompanied by an increase in the number of dendritic cells. Tear PGRN levels were also significantly lower in patients with diabetes than in normal controls, and the levels of some inflammatory factors (TNF-α, IL-6, and MMP-9) were higher in patients with DR. Remarkably, the PGRN level significantly correlated with nerve fiber density (R = 0.48, P < 0.001), nerve fiber length (R = 0.65, P < 0.001), and nerve branch density (R = 0.69, P < 0.001). Tear PGRN levels might reflect morphological changes in the corneal nerve plexus under diabetic conditions, suggesting that PGRN itself is a reliable indicator for predicting the advancement of neurotrophic keratopathy in patients with diabetes. PGRN insufficiency on the ocular surface under diabetic conditions was found to be closely associated with nerve impairment, providing a novel perspective to discover the pathogenesis of diabetic complications, which could help in developing innovative therapeutic strategies.

A highly selective inhibitor of discoidin domain receptor-1 (DDR1-IN-1) protects corneal epithelial cells from YAP/ACSL4-mediated ferroptosis in dry eye.

This study investigated the involvement of discoidin domain receptor (DDR) in dry eye and assessed the potential of specific DDR inhibitors as a therapeutic strategy for dry eye by exploring the underlying mechanism. Dry eye was induced in Wistar rats by applying 0.2% benzalkonium chloride (BAC), after which rats were treated topically for 7 days with DDR1-IN-1, a selective inhibitor of DDR1. Clinical manifestations of dry eye were assessed on Day-7 post-treatment. Histological evaluation of corneal damage was performed using haematoxylin and eosin (H&E) staining. In vitro, immortalized human corneal epithelial cells (HCECs) exposed to hyperosmotic stress (HS) were treated with varying doses of DDR1-IN-1 for 24 h. The levels of lipid peroxidation in dry eye corneas or HS-stimulated HCECs were assessed. Protein levels of DDR1/DDR2 and related pathways were detected by western blotting. The cellular distribution of acyl-CoA synthetase long chain family member 4 (ACSL4) and Yes-associated protein (YAP) was evaluated using immunohistochemistry or immunofluorescent staining. In dry eye corneas, only DDR1 expression was significantly up-regulated compared with normal controls. DDR1-IN-1 treatment significantly alleviated dry eye symptoms in vivo. The treatment remarkably reduced lipid hydroperoxide (LPO) levels and suppressed the expression of ferroptosis markers, particularly ACSL4. Overexpression or reactivation of YAP diminished the protective effects of DDR1-IN-1, indicating the involvement of the Hippo/YAP pathway in DDR1-targeted therapeutic effects. This study confirms the significance of DDR1 in dry eye and highlights the potential of selective DDR1 inhibitor(s) for dry eye treatment.

Value of Anterior Segment Ocular Coherence Tomography (AS-OCT) in Dryness Evaluation in Vitiligo

Abstract Background Vitiligo is an acquired depigmentation disorder of the skin and mucous membranes with an autoimmune proposed pathogenesis. The concurrence of vitiligo and ocular abnormalities has been investigated in different studies, some of which have focused on ocular surface and dry eye evaluation in vitiligo. Aim of the Work Our study aimed at evaluating the tear film changes in patients with vitiligo using clinical assessment, severity indices and AS-OCT, and comparing these findings with healthy matching controls. Patients and Methods A case control observational study that included 60 eyes (the right eye of 30 patients with vitiligo and the right eye of 30 healthy age and sex matched controls). For every patient full dermatological assessment was done and drug history taken. Every study subject was evaluated regarding their dry eye symptomatology using the (OSDI) score questionnaire, clinical effect of dry eye in various tests (Schirmer’s test, TBUT, CFS using Oxford scheme), and using the AS OCT in measuring tear film height. Results We found that vitiligo patients had a lower tear film height when compared with controls (but statistically insignificant). Patients with vitiligo were more symptomatic regarding their dry eye symptoms assessed by OSDI score, they had a shorter tear breakup time than the control group, and a higher CFS grade using Oxford scheme indicating tear film instability. Conclusion Our study revealed lower, but statistically insignificant TFH as compared to the control group. TBUT was shorter, CFS was more evident and Schirmer’s test (although did not reach statistical significance) was shorter in vitiligo patients which revealed a tendency for dry eye syndrome. Supporting these findings, the OSDI score was higher in vitiligo patients. These results indicated worse symptomatology of dry eye in vitiligo patients and lack of stability of their tear film. The findings were supported by multiple previous studies mentioned earlier.

The severity of dry eye symptoms and risk factors among university students in Saudi Arabia: a cross-sectional study

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.

Closing Eyes with Artificial Tears: A Simple and Effective Strategy to Combat Screen-Related Asthenopia and Dry Eye Symptoms

BackgroundThe widespread use of various video display terminals (VDTs) always had a detrimental impact on ocular health. Prolonged use of smartphones has been one of the leading causes of dry eye (DE) and asthenopia. Therefore, the purpose of this study is to find a simple and effective strategy to combat screen-related DE and asthenopia. MethodsA group of healthy participants aged 18 and above were randomly assigned to three groups and tasked with a 2-hour smartphone reading task. After 1 hour of usage, each group adopted different methods of rest: no rest (Group A), a 10-minute eye-closed rest (Group B), or a 10-minute eye-closed joint artificial tears rest (Group C). Ophthalmological examinations and questionnaires were administered to all participants before and after the 2-hour reading task. Results90 qualified volunteers, including 29 males and 61 females, were randomly assigned to three groups. Group A demonstrated a significant increase in the severity of DE and asthenopia as evidenced by all the evaluated indices. On the other hand, Group C did not exhibit any notable change in DE and asthenopia symptoms, with an improvement in corneal fluorescein staining (CFS) results (p > 0.05) when compared to the pre-reading values. Group B showed a significant increase in ocular surface disease index (OSDI) (p ≤ 0.05) and a decrease in critical flicker frequency (CFF) (p ≤ 0.05). ConclusionsClose-eye rest with artificial tears may be a convenient and effective prevention strategy for screen-related DE and asthenopia.