The effect of hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer eyedrops on inflammatory cytokine expression in tears of patients with computer vision syndrome

The effect of hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer eyedrops on inflammatory cytokine expression in tears of patients with computer vision syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The effect of hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer eyedrops on inflammatory cytokine expression in tears of patients with computer vision syndrome Shikha Pawaiya, Divya Singh, Vinod Sharma, Bhavya Mehta, Rahul Bhargava, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6953604/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: To examine the impact of hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer eyedrops on inflammatory cytokines in the tears of individuals experiencing computer vision syndrome. Methods : A randomized, double-masked, multi-center interventional study was conducted. One hundred sixteen computer users with symptoms (using computers over 3 hours daily for at least 1 year) were randomized into two groups; 56 patients recei ved HPG-HA eyedrops, and 60 patients received preserved saline drops, both twice daily for duration of 3 months. The primary outcome was the reduction of inflammatory cytokines (IL-1β, IL2, IL4, IL5, IL6, IL8, IL10, IF-γ, TNF-α) in conjunctiva and tears of computer users. Secondary outcomes encompassed alterations in dry eye symptom scores, Schirmer test results, TBUT values, and Nelson grade at the 3-month mark. Results : At baseline, tear inflammatory cytokines and tear film parameters were similar in both the supplement and placebo groups. Tear inflammatory cytokine levels showed no significant changes from baseline at three months post-intervention in the tear supplement group, despite numerical reduction. However, the tear supplement group demonstrated a notable improvement in dry eye symptoms (P < 0.001), Schirmer test scores (P < 0.001), and TBUT scores (P < 0.001); however, there was no significant alteration in goblet cell counts or morphology og conjunctival epithelial cells. Conclusion : Treatment with hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer eyedrops for 3 months does alleviates dry eye symptoms and decreases tear evaporation rate in patients with computer vision syndrome. However, it does not alter tear inflammatory cytokines nor increase conjunctival goblet cell density. Computer vision syndrome dry eye tear cytokines goblet cell density Figures Figure 1 Figure 2 Introduction Several factors can affect ocular surface health, such as contact lens wear, refractive surgical procedures, and extended computer use. Post-COVID-19, personal computer use has skyrocketed in schools, offices, and homes. People of all ages-children, students, professionals, and seniors-spend 2 to 12 hours daily on computers, with mobile phone usage adding to this load. Individuals with computer vision syndrome may exhibit symptoms like eye strain, fatigue, headache, dryness of eyes, redness, foreign body sensation, blurred vision, and occasionally backache and neck pain. Computer vision syndrome is a public health issue that adversely impacts quality of life related to vision [ 1 ]. A study by Hagan et al [ 2 ]. found that the prevalence of dry eye symptoms in men and women using computers ranged from 68–73%. Prolonged use of computers and the resulting tear film instability can lead to tear hyperosmolarity, damage to the ocular surface epithelium, and an increase in inflammatory mediators such as interleukins and cytokines [ 3 – 5 ]. A significantly elevated IL-6 levels in their tears of patients with ocular surface disorders as compared to controls were revealed in a recent meta-analysis [ 6 ]. Eye drops containing lubricants do offer temporary relief from dry eye symptoms caused by computer vision syndrome [ 7 ]. It remains unclear whether there is any change in inflammatory tear cytokines/chemokines or alterations in conjunctival goblet cell density after treatment with these supplements. The aim of this randomized double-masked study was to assess whether tear supplements containing hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer reduce inflammatory cytokines/chemokines in tears and enhance limbal cytology and morphology (via impression cytology), in symptomatic computer users compared to a placebo (preserved saline drops). Methods At three eye centres in the subcontinent, a multi-centre, randomized, double-masked study was conducted. The trial received approval from the ethics boards, and all patients provided written informed consent as per the tenets of the declaration of Helsinki. The trial was registered with the clinical trial registry (UMIN); trial ID UMIN0000360042. Criteria for inclusion Computer users with symptoms (using computers for over 3 hours a day for at least 1 year) were selected for the trial. Enrolment was based on the Indian dry eye questionnaire (Dry Eye Scoring System, DESS©) [ 8 ]. Criteria for Exclusion Patients suffering from ocular infections, prior LASIK surgery, allergic conjunctivitis, contact lens use, herpetic eye disease, diabetes, or liver diseases were excluded. Patients having fluorescein allergy were also excluded. Drugs (tetracyclines, corticosteroids, omega-3 fatty acids), and topical treatments affecting tear film profile were stopped before the intervention. Patients also avoided rehydrating eye drops for 12 hours before testing. Outcome measures Patients were assessed initially and again 3 months after beginning treatment. The main outcome measured was the decrease in inflammatory markers in the tears and conjunctiva of computer users after 3 months compared to baseline levels. The cytokines/chemokines measured included IL-1β, IL2, IL4, IL5, IL6, IL8, IL10, IF-γ, and TNF-α. Secondary outcomes at 3 months included changes in dry eye symptom scores, production of tears (Schirmer test), stability of tear film (TBUT), and conjunctival epithelial cell morphology and goblet cell counts. Dry eye symptoms were scored from 0 to 3 for ocular fatigue, vision blurring, itching or burning, sandy or gritty sensation, and redness (DESS©). Scores: absent (0), sometimes present (1), frequently present (2), always present (3). Dry eye severity: mild (0–6), moderate (6.1–12), severe (12.1–18) (Fig. 1 ). Ocular Examination and measurements Participants visited the dry eye clinic between 10 AM and 12 PM. One eye per patient was selected randomly for examination. Participants were assessed at 22 ± 1.4°C with 48 ± 10% relative humidity. An independent investigator thoroughly examined the eyes, noting visual acuity and inspecting the lid margins, eyelashes, and meibomian gland openings for blockages. Tear film tests Tear film evaluations were conducted before tear collection and patients completed the Indian dry eye questionnaire (DESS). The investigator conducting all clinical evaluations was masked to the treatment group of participants. The Tear Breakup Time (TBUT) was measured initially to avoid the influence of eyelid manipulation on the results. A fluorescein strip wetted with saline was placed over the lower conjunctiva. Patients were instructed to blink to evenly distribute the fluorescein, and the tear film was subsequently examined using a cobalt blue filter on a slit lamp. The time between the last blink and the first dry spot on the cornea was recorded, averaging three readings. A TBUT under 10 seconds suggests dry eye syndrome. After a 30-minute interval, a Schirmer test was conducted using 0.4% oxybuprocaine with the eyes closed. A result of less than 6 mm wetting also confirmed a diagnosis of dry eye syndrome. Tear collection A tear sample (non-stimulated) was collected using a 5-mL microcapillary from the lower lid's marginal tear strip near the lateral canthus, ensuring avoidance of contact with neighbouring structures (conjunctiva, cornea, or lid margin). Tears (20 µL) were collected from one eye and stored at -70°C in microtubes. The samples were diluted tenfold using assay diluent for the experiment. A volume of 100 µL per sample was utilized to measure IL-1𝛽, IL2, IL4, IL5, IL6, IL8, IL10, IF-γ, and TNF-𝛼. Tear cytokines Tear cytokine levels were quantified utilizing a Quansys Biosciences 10-plex assay kit, capable of detecting IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, and TNFα. Following the manufacturer's guidelines, serum samples were thawed, centrifuged, and analyzed. Cytokine levels in 100 µL samples were measured using ELISA-based chemiluminescence. Absorbance was measured using Q-View Imager and QView™ Software. The ranges for detecting cytokines were IL‑1β (29–218 pg/mL), IL‑2 (2.13–5000 pg/mL), IL‑4 (1.37–4500 pg/mL), IL‑5 (1.55–4500 pg/mL), IL‑6 (0.02–3000 pg/mL), IL‑8 (0.16–2800 pg/mL), IL‑10 (0.25–3300 pg/mL), IF-γ(1.8–3800 pg/mL), and TNF‑α (1.02–4000 pg/mL). Conjunctival impression cytology An examiner conducted CIC using a standard technique as described previously [ 9 – 10 ]. Slides were viewed first under a light microscope at 100X magnification and then at 400X magnification to analyse cells. A minimum of 10 high-power fields (HPFs) were analyzed to assess the presence of goblet and epithelial cells. The number of goblet cells per HPF was counted, and the goblet cell density (GCD) was estimated by dividing the goblet cells per HPF by the sampling area in square millimetres. Using Nelson's criteria, grades 0 and 1 were considered normal, and grades 2 and 3 were deemed abnormal. Both computer user groups (n = 5 each) were examined for IL-1β, IL-6, IL-8, and TNF-α mRNA expression in impression cytology specimens using QuantiTect SYBR Green real-time PCR (Qiagen) to determine the inflammatory cytokine source. Sample size calculation, randomization, and masking In order to determine the sample size required for comparing the mean difference in IL-6 levels between two groups, an initial pilot study was conducted with 10 subjects. The mean decrease in IL-6 score in tear supplement group (Group 1) was 0.83 and in placebo group (Group 2) 0.69, respectively. The standard deviation was 0.47. With 1:1 randomization, 90% power (alpha = 0.05), and a precision error of 5% to detect a difference of 20% or more in IL-6 between the groups, the estimated sample size for each group was calculated to be 46. A total of 116 eligible participants were recruited, surpassing the minimum sample size needed to attain the intended study power. Allocation codes were generated through software within our community medicine department. Stratification was conducted based on clinical center, employing a permuted-block method with variable block sizes. Patients were randomly assigned to two groups using parallel assignment. Healthcare personnel not involved in patient care opened sealed RED envelopes containing the allocation codes. Group 1 was administered an artificial tear solution comprising hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer (Systane hydration, Alcon Singapore Pvt Ltd, South Avenue, Singapore 637313) eye drops twice daily over a period of three months. Conversely, the placebo group received preserved saline drops (Rinsol, Gaymed Labs pvt Ltd, Delhi, India) with identical frequency. Both participants and investigators were blinded to the treatment allocations. The bottles for both types of eye drops were designed to appear similar. Non-care health staff evaluated patient compliance. At each monthly visit, subjects returned bottles, measured remaining eye drops, and received new packs. Subjects were told to keep a standard diet and avoid extra supplements. Statistics The IBM SPSS Statistics version 29 statistical software was used for data analysis. Independent t-tests verified baseline group similarities. Chi-square tests were applied to proportions. Normally distributed data were reported as mean ± standard deviation (SD). The data that was not normally distributed underwent a box-cox transformation. Linear regression with a robust variance estimator compared mea n changes in continuous variables between groups. A one-way repeated-measures ANOVA assessed mean test value differences over 3 months (tear supplement vs. placebo). Mauchly's test indicated sphericity violation, χ2(2) = 6.27, p = .043, requiring a Greenhouse-Geisser correction (ε = 0.648). A post hoc Tukey test with Bonferroni correction identified differences. P-value below 0.005 was considered to indicate statistical significance. Results Out of 134 patients, 18 were lost to follow-up. Group 1 (tear supplement group) had 56 subjects, and Group 2 (placebo) had 60 subjects. 104 patients completed the 3-month follow-up, with cost constraints causing 12 dropouts. The study included 46 males and 58 females. Table 1 indicates that the baseline test values for IL‑1β, IL‑2, IL‑4, IL‑5, IL‑6, IL‑8, IL‑10, IF-γ, and TNFα, as well as tear film parameters such as Schirmer, TBUT, Nelson grade, and GCD, were comparable between the groups receiving the tear substitute and those receiving the placebo. On impression cytology, the mRNA expression levels of IL-1 β, IL-6, IL-8, and TNF-α exhibited an increase ranging from 1.4 to 2-fold at baseline. At baseline, 36% of patients in the tear substitute group showed abnormal Schirmer tests, compared to 34% in the placebo group. Abnormal TBUT was seen in 58% of the tear substitute group versus 56% in the placebo group. Thirty-six percent of the tear substitute group had abnormal cytology, compared to 34% in the placebo group. WITHIN GROUP COMPARISONS Repeated-measures ANOVA showed no significant difference in mean cytokine levels or GCD from baseline at 3 months after-intervention in Group 1. A Bonferroni-adjusted post hoc analysis confirmed that tear cytokines and GCD did not significantly change from baseline to 1 month or from baseline to 3 months after intervention (Table 2). Notably, there was a significant improvement in dry eye symptoms, Schirmer’s test scores, and TBUT after three months. In the placebo group, repeated-measures ANOVA showed no significant change in mean cytokine levels or GCD from baseline at 3 months post-intervention. Bonferroni-adjusted post hoc analysis also indicated no significant changes in tear cytokines and GCD from baseline to 1 month or 3 months after intervention (Table 3). Dry eye symptoms and TBUT improved after 3 months in the placebo group as well. BETWEEN GROUP COMPARISONS Table 4 compares mean test values between Group 1 and Group 2 after 3 months of intervention. No significant differences were observed in tear cytokines and GCD. However, Group 1 showed significant improvements in dry eye symptoms, Schirmer test score, and TBUT (P<0.001). The placebo group also experienced better dry eye symptoms. Goblet cell density After 3 months, Group 1 showed no significant increase in goblet cell density or nuclear-cytoplasmic ratio of conjunctival epithelial cells. (Figure 2a and 2b). The placebo group also showed no significant changes in these two parameters. Discussion This placebo-controlled, randomized, double-masked study examined whether treatment with HPG-HA tear supplements for 3 months alter inflammatory cytokines/chemokines in patients suffering from computer vision syndrome. This study found that computer users with symptoms had higher baseline tear cytokine levels. Additionally, using HPG-HA tear supplements did not significantly change inflammatory cytokine or chemokine levels in their tears. After 3 months of intervention, there was improvement in dry eye symptoms, tear production and tear film stability; however, no changes were observed morphologically in conjunctival epithelial cells (nuclear-cytoplasmic ratio) or goblet cell counts. Prolonged computer use is known to cause ocular surface inflammation; this is evidenced by presence of mediators like prostaglandins (PGE2), interleukins (IL-1), and leukotrienes in tears [ 11 ]. Additionally, chronic inflammation of the ocular surface may lead to alteration of epithelial cell morphology and reduction conjunctival goblet cell count [ 12 – 13 ]. Numerous artificial tear formulations, differing in composition and viscosity, are available in various forms including gels, ointments, and drops. They help maintain the tear film by supplementing its layers, reducing evaporation, stabilizing it, and lubricating the eyes to prevent complications [ 14 – 15 ]. However, they do not modify tear cytokines, increase nuclear cytoplasmic ratio (reverse metaplastic changes) in conjunctival epithelial cells, or increase goblet cell counts [ 16 – 17 ]. A study conducted by Duan et al observed decreased mRNA expression of MUC1, MUC16, and MUC20 in the conjunctival impression cytology (CIC) specimens of symptomatic VDT users, compared to VDT users who did not meet the criteria for DED [ 18 ]. Changes in inflammatory cytokines after topical and dietary interventions have not been studied in the tears of symptomatic computer users. Research have shown that presence of elevated levels of IL-1, IL-6, IL-8, IFN-γ, and TNF-α in the conjunctival epithelium is linked to dry eye. These studies have primarily concentrated on Sjogren syndrome with aqueous deficient dry eye [ 19 – 20 ]. Only a few studies have documented alteration in cytokines in the tears of people suffering from computer vision syndrome. A study conducted by Ribelles et al found that older women who work on computers for extended hours exhibit significantly higher levels of IL-1β and IL-6 compared to those who do not engage in computer work [ 21 ]. This indicated an appropriate inflammatory response in the tears of these patients who frequently use computers. Women taking antioxidants and omega-3 fatty acids showed significantly lower levels of inflammatory cytokines. A study by Bhargava et al reported that oral administration of anti-inflammatory omega-3 fatty acids can reduce dry eye symptoms, lower tear evaporation rate, and improve Nelson grade in young individuals who use computers for more than 3 hours per day for at least 1 year [ 22 ]. The study suggested that ocular surface inflammation might be a key factor in computer vision syndrome-related dry eye, but did not evaluate tear cytokines and chemokines due to cost constraints. Our study had limitations and strengths. The patients were not evaluated in controlled conditions; the impact of environmental confounding variables could not be excluded. A randomized controlled study design was our strength. This study is the first to evaluate in inflammatory cytokine expression in computer vision syndrome patients following intervention (Medline Search). Due to cost constraints, not all inflammatory cytokines/chemokines could be analyzed. In conclusion, treatment with HPG-HA dual-polymer eyedrops for 3 months did not change tear inflammatory cytokines or increase conjunctival goblet cell density in patients suffering from computer vision syndrome. Declarations Source of Support : Nil Conflict of interest : None Acknowledgements : We thank for statistical analysis References Jaiswal S, Asper L, Long J, Lee A, Harrison K, Golebiowski B (2019). Ocular and visual discomfort associated with smartphones, tablets and computers: what we do and do not know. Clin Exp Optom. 10:463-477. Hagan S, Lory B (1998). Prevalence of dry eye among computer users. Optom Vis Sci. 75:712-3. Massingale ML, Li X, Vallabhajosyula M, Chen D, Wei Y, Asbell PA (2009). Analysis of inflammatory cytokines in the tears of dry eye patients. Cornea. 28:1023-7. Cardona G, Argilés M, Pérez-Cabré E (2023). Loss of Blink Regularity, and Its Impact on Ocular Surface Exposure. Diagnostics (Basel). 13:2362. Schlote T, Kadner G, Freudenthaler N (2004). Marked reduction and distinct patterns of eye blinking in patients with moderately dry eyes during video display terminal use. Graefes Arch Clin Exp Ophthalmol 242:306-12. Ulhaq ZS, Soraya GV, Budu, Wulandari LR (2020). The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis. Sci Rep. 2020; 10:17453. Craig JP, Muntz A, Wang MTM, Luensmann D, Tan J, Trave Huarte S, et al (2021). Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial. Ocul Surf. 20:62-69. Bhargava R, Kumar P (2015). Oral omega-3 fatty acid treatment for dry eye in contact lens wearers. Cornea. 34:413-20. Bhargava R, Pandey K, Ranjan S, Mehta B, Malik A (2023). Omega-3 fatty acids supplements for dry eye - Are they effective or ineffective? Indian J Ophthalmol. 71:1619-1625. Bhargava R, Rajpoot M, Arora Y, Sharma SK, Sharma S (2017). Dietary Omega-3 Fatty Acids Supplements for Dry Eye in Psoriasis: Are they Effective? J Clin of Diagn Res. 11(11):NC01-NC05. The definition and classification of dry eye disease (2007): Report of the definition and classification subcommittee of the international dry eye workshop. Ocul Surf 5:75–92. Apostol S, Filip M, Dragne C, Filip A (2003). Dry eye syndrome. Etiological and therapeutic aspects. Oftalmologia. 2003; 59:28-31. Jones L, Downie LE, Korb D, Dana R, Deng S, Dong P, et al (2017). TFOS DEWS II Management and Therapy Report. Ocul Surf 15:575–628. Pucker AD, Ng SM, Nichols JJ (2016). Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev :CD009729. Kumar P, Bhargava R, Kumar M, Ranjan S, Kumar M, Verma P (2014). The correlation of routine tear function tests and conjunctival impression cytology in dry eye syndrome. Korean J Ophthalmol 28:122–129. Maity M, Galor A, Basu S, Singh S (2024). Tear Film Dynamics in Visual Display Terminal Users: A Review of Impact on Goblet Cells, Lacrimal and Meibomian Gland Function. Semin Ophthalmol:1-14. Duan H, Yang T, Zhou Y, Ma B, Zhao L, Chen J, Qi H (2023). Comparison of mucin levels at the ocular surface of visual display terminal users with and without dry eye disease. BMC Ophthalmol. 23:189. Massingale ML, Li X, Vallabhajosyula M, Chen D, Wei Y, Asbell PA (2009). Analysis of inflammatory cytokines in the tears of dry eye patients. Cornea.28(9):1023-7. Pflugfelder SC, Jones D, Ji Z, Afonso A, Monroy D (1999). Altered cytokine balance in the tear fluid and conjunctiva of patients with Sjögren's syndrome keratoconjunctivitis sicca. Curr Eye Res 19:201-11. Solomon A, Dursun D, Liu Z, Xie Y, Macri A, Pflugfelder SC (2001). Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. Invest Ophthalmol Vis Sci.42:2283-92. Ribelles A, Galbis-Estrada C, Parras MA, Vivar-Llopis B, Marco-Ramírez C, Diaz-Llopis M (2015). Ocular Surface and Tear Film Changes in Older Women Working with Computers. Biomed Res Int. 2015:467039. Bhargava R, Kumar P, Phogat H, Kaur A, Kumar M (2015). Oral omega-3 fatty acids treatment in computer vision syndrome related dry eye. Cont Lens Anterior Eye 38:206-10. Tables Table 1. Key characteristics (baseline) *Measure Group 1(tear supplement) Group 2 (Placebo) t-test P value Age (years) 23.1±1.7 23.8±1.9 0.057 IL1β 523±47.5 522.3±47 0.943 IL2 131.6±5.1 134±5.5 0.056 IL4 364.6±7.3 366.4±18 0.064 IL5 264.8±13 266.3±14 0.083 IL6 1404±4.6 1400±4.8 0.078 IL8 473±30 474.8±34 0.069 IL10 452±13.5 458±44 0.146 IF γ 320±16.8 322±16 0.666 TNFα 344±32 346±44 0.234 DESS Score 7.6±1.6 7.4±1.5 0.539 Schirmer 17.3±1.8 17.5±1.9 0.548 TBUT 11.8±2 12.1±2.3 0.467 Nelson Grade 1.2±0.28 1.25±0.29 0.303 GCD (cells/mm2) 780±21 783±20.5 0.344 The data is presented as mean ± standard deviation, TBUT (tear film break up time) and GCD (Goblet cell density, cells/mm²). Table 2. Group 1 mean test values at 6 months post-intervention *Measure Baseline 6 months post intervention t-test P value IL1β 523±47.5 518±51.2 0.632 IL2 131.6±5.1 129±5.9 0.093 IL4 364.6±7.3 361±11.1 0.173 IL5 264.8±4 262±9.6 0.105 IL6 1404±4.6 1401±9.7 0.125 IL8 473±3.0 470±9.7 0.116 IL10 452±13.5 450±18 0.437 IF γ 320±16.8 316±16.7 0.266 TNFα 344±8.7 342±8.6 0.175 DESS Score 7.6±1.6 1.2±1 0.001 Schirmer 17.3±1.8 19.9±1.4 0.001 TBUT 11.8±2 15.4±2.1 0.001 Nelson Grade 1.2±0.28 1.16±0.3 0.503 GCD (cells/mm2) 780±21 774±26.6 0.281 * The data is presented as mean ± standard deviation, TBUT (tear film break up time) and GCD (Goblet cell density, cells/mm²). Table 3 . Mean test values at 3 months after intervention (Group 2) *Measure Baseline 3 months post intervention t-test P value IL1β 522.3±47 524±45.7 0.836 IL2 134±5.5 135±5.3 0.362 IL4 366.4±18 365±5.2 0.526 IL5 266±4.7 264±4.4 0.072 IL6 1400±4.8 1399±6.4 0.058 IL8 474.8±34 473.5±3.7 0.101 IL10 458±4.4 456±4.7 0.839 IF γ 322±16 319±14.2 0.789 TNFα 346±4.4 344±4.3 0.654 DESS Score 7.4±1.5 5.2±1.5 0.001 Schirmer 17.5±1.9 17.8±1.8 0.357 TBUT 12.1±2.3 13.8±2.4 0.049 Nelson Grade 1.25±0.29 1.2±0.27 0.282 GCD (cells/mm2) 783±20.5 780±21.8 0.469 * The data is presented as mean ± standard deviation, TBUT (tear film break up time) and GCD (Goblet cell density, cells/mm²). Table 4. Mean test values at 3 months post-intervention *Parameter Group 1(tear supplement) Group 2 (Placebo) P value (independent t -test) IL1β 518±51.2 524±45.7 0.533 IL2 129±5.9 135±5.3 0.131 IL4 361±11.1 365±5.2 0.261 IL5 262±9.6 264±4.4 0.057 IL6 1401±9.7 1399±6.4 0.238 IL8 470±9.7 473.5±3.7 0.068 IL10 450±18 456±4.7 0.090 IF γ 316±16.7 319±14.2 0.268 TNFα 342±8.6 344±6.3 0.136 DESS Score 3.8±0.52 5.2±1.5 0.001 Schirmer 19.9±1.4 17.8±1.8 0.001 TBUT 15.4±2.1 13.8±2.4 0.001 Nelson Grade 1.16±0.3 1.2±0.27 0.242 GCD (cells/mm2) 774±26.6 780±21.8 0.099 *Expressed as mean ± standard deviation, TBUT (tear film break up time), GCD (Goblet cell density (cells/mm2). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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10:20:06","extension":"html","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":122378,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-6953604/v1/b459169afc927f759b4163d0.html"},{"id":91846674,"identity":"8e843bda-4f29-4812-a3b5-d95524ba1cbc","added_by":"auto","created_at":"2025-09-22 10:20:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":101538,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6953604/v1/b7931500e75ecdd7196f3d7f.png"},{"id":91847812,"identity":"88dfb21f-8945-4fc4-a520-11a5d31f821c","added_by":"auto","created_at":"2025-09-22 10:28:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":598849,"visible":true,"origin":"","legend":"\u003cp\u003ea. Baseline photomicrograph of impression cytology specimen stained with periodic acid-Schiff and hematoxylin-eosin at X 400 showing squamous metaplasia (SM). Red arrow indicates a normal cell (NC) and black arrow indicates reduced nuclear–cytoplasmic ratio (SM).\u003c/p\u003e\n\u003cp\u003eb. Photomicrographs of impression cytology specimens, stained with periodic acid-Schiff and hematoxylin-eosin at X 400 magnification, showing persistent squamous metaplasia and decreased goblet cell density three months post-intervention.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6953604/v1/e0c80dbea2a8d92f29f2bec4.png"},{"id":92060289,"identity":"28203844-7a7b-403a-86db-0695af926116","added_by":"auto","created_at":"2025-09-24 08:02:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1616750,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6953604/v1/45ff66d9-d3cd-41ee-94a2-0103c061a12a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The effect of hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer eyedrops on inflammatory cytokine expression in tears of patients with computer vision syndrome","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSeveral factors can affect ocular surface health, such as contact lens wear, refractive surgical procedures, and extended computer use. Post-COVID-19, personal computer use has skyrocketed in schools, offices, and homes. People of all ages-children, students, professionals, and seniors-spend 2 to 12 hours daily on computers, with mobile phone usage adding to this load.\u003c/p\u003e\u003cp\u003eIndividuals with computer vision syndrome may exhibit symptoms like eye strain, fatigue, headache, dryness of eyes, redness, foreign body sensation, blurred vision, and occasionally backache and neck pain. Computer vision syndrome is a public health issue that adversely impacts quality of life related to vision [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eA study by Hagan et al [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. found that the prevalence of dry eye symptoms in men and women using computers ranged from 68\u0026ndash;73%. Prolonged use of computers and the resulting tear film instability can lead to tear hyperosmolarity, damage to the ocular surface epithelium, and an increase in inflammatory mediators such as interleukins and cytokines [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eA significantly elevated IL-6 levels in their tears of patients with ocular surface disorders as compared to controls were revealed in a recent meta-analysis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eEye drops containing lubricants do offer temporary relief from dry eye symptoms caused by computer vision syndrome [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. It remains unclear whether there is any change in inflammatory tear cytokines/chemokines or alterations in conjunctival goblet cell density after treatment with these supplements.\u003c/p\u003e\u003cp\u003eThe aim of this randomized double-masked study was to assess whether tear supplements containing hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer reduce inflammatory cytokines/chemokines in tears and enhance limbal cytology and morphology (via impression cytology), in symptomatic computer users compared to a placebo (preserved saline drops).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eAt three eye centres in the subcontinent, a multi-centre, randomized, double-masked study was conducted. The trial received approval from the ethics boards, and all patients provided written informed consent as per the tenets of the declaration of Helsinki. The trial was registered with the clinical trial registry (UMIN); trial ID UMIN0000360042.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eCriteria for inclusion\u003c/h2\u003e\u003cp\u003eComputer users with symptoms (using computers for over 3 hours a day for at least 1 year) were selected for the trial. Enrolment was based on the Indian dry eye questionnaire (Dry Eye Scoring System, DESS\u0026copy;) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eCriteria for Exclusion\u003c/h3\u003e\n\u003cp\u003ePatients suffering from ocular infections, prior LASIK surgery, allergic conjunctivitis, contact lens use, herpetic eye disease, diabetes, or liver diseases were excluded. Patients having fluorescein allergy were also excluded. Drugs (tetracyclines, corticosteroids, omega-3 fatty acids), and topical treatments affecting tear film profile were stopped before the intervention. Patients also avoided rehydrating eye drops for 12 hours before testing.\u003c/p\u003e\n\u003ch3\u003eOutcome measures\u003c/h3\u003e\n\u003cp\u003ePatients were assessed initially and again 3 months after beginning treatment. The main outcome measured was the decrease in inflammatory markers in the tears and conjunctiva of computer users after 3 months compared to baseline levels. The cytokines/chemokines measured included IL-1β, IL2, IL4, IL5, IL6, IL8, IL10, IF-γ, and TNF-α.\u003c/p\u003e\u003cp\u003eSecondary outcomes at 3 months included changes in dry eye symptom scores, production of tears (Schirmer test), stability of tear film (TBUT), and conjunctival epithelial cell morphology and goblet cell counts.\u003c/p\u003e\u003cp\u003eDry eye symptoms were scored from 0 to 3 for ocular fatigue, vision blurring, itching or burning, sandy or gritty sensation, and redness (DESS\u0026copy;). Scores: absent (0), sometimes present (1), frequently present (2), always present (3). Dry eye severity: mild (0\u0026ndash;6), moderate (6.1\u0026ndash;12), severe (12.1\u0026ndash;18) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eOcular Examination and measurements\u003c/h3\u003e\n\u003cp\u003eParticipants visited the dry eye clinic between 10 AM and 12 PM. One eye per patient was selected randomly for examination. Participants were assessed at 22\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u0026deg;C with 48\u0026thinsp;\u0026plusmn;\u0026thinsp;10% relative humidity.\u003c/p\u003e\u003cp\u003eAn independent investigator thoroughly examined the eyes, noting visual acuity and inspecting the lid margins, eyelashes, and meibomian gland openings for blockages.\u003c/p\u003e\n\u003ch3\u003eTear film tests\u003c/h3\u003e\n\u003cp\u003eTear film evaluations were conducted before tear collection and patients completed the Indian dry eye questionnaire (DESS). The investigator conducting all clinical evaluations was masked to the treatment group of participants. The Tear Breakup Time (TBUT) was measured initially to avoid the influence of eyelid manipulation on the results. A fluorescein strip wetted with saline was placed over the lower conjunctiva. Patients were instructed to blink to evenly distribute the fluorescein, and the tear film was subsequently examined using a cobalt blue filter on a slit lamp. The time between the last blink and the first dry spot on the cornea was recorded, averaging three readings. A TBUT under 10 seconds suggests dry eye syndrome.\u003c/p\u003e\u003cp\u003eAfter a 30-minute interval, a Schirmer test was conducted using 0.4% oxybuprocaine with the eyes closed. A result of less than 6 mm wetting also confirmed a diagnosis of dry eye syndrome.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eTear collection\u003c/h2\u003e\u003cp\u003eA tear sample (non-stimulated) was collected using a 5-mL microcapillary from the lower lid's marginal tear strip near the lateral canthus, ensuring avoidance of contact with neighbouring structures (conjunctiva, cornea, or lid margin). Tears (20 \u0026micro;L) were collected from one eye and stored at -70\u0026deg;C in microtubes.\u003c/p\u003e\u003cp\u003eThe samples were diluted tenfold using assay diluent for the experiment. A volume of 100 \u0026micro;L per sample was utilized to measure IL-1\u0026#120573;, IL2, IL4, IL5, IL6, IL8, IL10, IF-γ, and TNF-\u0026#120572;.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eTear cytokines\u003c/h3\u003e\n\u003cp\u003eTear cytokine levels were quantified utilizing a Quansys Biosciences 10-plex assay kit, capable of detecting IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, and TNFα. Following the manufacturer's guidelines, serum samples were thawed, centrifuged, and analyzed. Cytokine levels in 100 \u0026micro;L samples were measured using ELISA-based chemiluminescence. Absorbance was measured using Q-View Imager and QView\u0026trade; Software.\u003c/p\u003e\u003cp\u003eThe ranges for detecting cytokines were IL‑1β (29\u0026ndash;218 pg/mL), IL‑2 (2.13\u0026ndash;5000 pg/mL), IL‑4 (1.37\u0026ndash;4500 pg/mL), IL‑5 (1.55\u0026ndash;4500 pg/mL), IL‑6 (0.02\u0026ndash;3000 pg/mL), IL‑8 (0.16\u0026ndash;2800 pg/mL), IL‑10 (0.25\u0026ndash;3300 pg/mL), IF-γ(1.8\u0026ndash;3800 pg/mL), and TNF‑α (1.02\u0026ndash;4000 pg/mL).\u003c/p\u003e\n\u003ch3\u003eConjunctival impression cytology\u003c/h3\u003e\n\u003cp\u003eAn examiner conducted CIC using a standard technique as described previously [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Slides were viewed first under a light microscope at 100X magnification and then at 400X magnification to analyse cells.\u003c/p\u003e\u003cp\u003eA minimum of 10 high-power fields (HPFs) were analyzed to assess the presence of goblet and epithelial cells. The number of goblet cells per HPF was counted, and the goblet cell density (GCD) was estimated by dividing the goblet cells per HPF by the sampling area in square millimetres. Using Nelson's criteria, grades 0 and 1 were considered normal, and grades 2 and 3 were deemed abnormal.\u003c/p\u003e\u003cp\u003eBoth computer user groups (n\u0026thinsp;=\u0026thinsp;5 each) were examined for IL-1β, IL-6, IL-8, and TNF-α mRNA expression in impression cytology specimens using QuantiTect SYBR Green real-time PCR (Qiagen) to determine the inflammatory cytokine source.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eSample size calculation, randomization, and masking\u003c/h2\u003e\u003cp\u003eIn order to determine the sample size required for comparing the mean difference in IL-6 levels between two groups, an initial pilot study was conducted with 10 subjects. The mean decrease in IL-6 score in tear supplement group (Group 1) was 0.83 and in placebo group (Group 2) 0.69, respectively. The standard deviation was 0.47. With 1:1 randomization, 90% power (alpha\u0026thinsp;=\u0026thinsp;0.05), and a precision error of 5% to detect a difference of 20% or more in IL-6 between the groups, the estimated sample size for each group was calculated to be 46. A total of 116 eligible participants were recruited, surpassing the minimum sample size needed to attain the intended study power.\u003c/p\u003e\u003cp\u003eAllocation codes were generated through software within our community medicine department. Stratification was conducted based on clinical center, employing a permuted-block method with variable block sizes. Patients were randomly assigned to two groups using parallel assignment. Healthcare personnel not involved in patient care opened sealed RED envelopes containing the allocation codes.\u003c/p\u003e\u003cp\u003eGroup 1 was administered an artificial tear solution comprising hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer (Systane hydration, Alcon Singapore Pvt Ltd, South Avenue, Singapore 637313) eye drops twice daily over a period of three months. Conversely, the placebo group received preserved saline drops (Rinsol, Gaymed Labs pvt Ltd, Delhi, India) with identical frequency. Both participants and investigators were blinded to the treatment allocations. The bottles for both types of eye drops were designed to appear similar. Non-care health staff evaluated patient compliance. At each monthly visit, subjects returned bottles, measured remaining eye drops, and received new packs. Subjects were told to keep a standard diet and avoid extra supplements.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eStatistics\u003c/h2\u003e\u003cp\u003eThe IBM SPSS Statistics version 29 statistical software was used for data analysis. Independent t-tests verified baseline group similarities. Chi-square tests were applied to proportions. Normally distributed data were reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). The data that was not normally distributed underwent a box-cox transformation. Linear regression with a robust variance estimator compared mea\u003cem\u003en\u003c/em\u003e changes in continuous variables between groups. A one-way repeated-measures ANOVA assessed mean test value differences over 3 months (tear supplement vs. placebo). Mauchly's test indicated sphericity violation, χ2(2)\u0026thinsp;=\u0026thinsp;6.27, p\u0026thinsp;=\u0026thinsp;.043, requiring a Greenhouse-Geisser correction (ε\u0026thinsp;=\u0026thinsp;0.648). A post hoc Tukey test with Bonferroni correction identified differences. P-value below 0.005 was considered to indicate statistical significance.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOut of 134 patients, 18 were lost to follow-up. Group 1 (tear supplement group) had 56 subjects, and Group 2 (placebo) had 60 subjects. 104 patients completed the 3-month follow-up, with cost constraints causing 12 dropouts. The study included 46 males and 58 females.\u003c/p\u003e\n\u003cp\u003eTable 1 indicates that the baseline test values for IL‑1β, IL‑2, IL‑4, IL‑5, IL‑6, IL‑8, IL‑10, IF-γ, and TNFα, as well as tear film parameters such as Schirmer, TBUT, Nelson grade, and GCD, were comparable between the groups receiving the tear substitute and those receiving the placebo.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOn impression cytology, the mRNA expression levels of IL-1 β, IL-6, IL-8, and TNF-α exhibited an increase ranging from 1.4 to 2-fold at baseline.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt baseline, 36% of patients in the tear substitute group showed abnormal Schirmer tests, compared to 34% in the placebo group. Abnormal TBUT was seen in 58% of the tear substitute group versus 56% in the placebo group. Thirty-six percent of the tear substitute group had abnormal cytology, compared to 34% in the placebo group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWITHIN GROUP COMPARISONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRepeated-measures ANOVA showed no significant difference in mean cytokine levels or GCD from baseline at 3 months after-intervention in Group 1. A Bonferroni-adjusted post hoc analysis confirmed that tear cytokines and GCD did not significantly change from baseline to 1 month or from baseline to 3 months after intervention (Table 2). Notably, there was a significant improvement in dry eye symptoms, Schirmer’s test scores, and TBUT after three months.\u003c/p\u003e\n\u003cp\u003eIn the placebo group, repeated-measures ANOVA showed no significant change in mean cytokine levels or GCD from baseline at 3 months post-intervention. Bonferroni-adjusted post hoc analysis also indicated no significant changes in tear cytokines and GCD from baseline to 1 month or 3 months after intervention (Table 3). Dry eye symptoms and TBUT improved after 3 months in the placebo group as well.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBETWEEN GROUP COMPARISONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4 compares mean test values between Group 1 and Group 2 after 3 months of intervention. No significant differences were observed in tear cytokines and GCD. However, Group 1 showed significant improvements in dry eye symptoms, Schirmer test score, and TBUT (P\u0026lt;0.001). The placebo group also experienced better dry eye symptoms.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGoblet cell density\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter 3 months, Group 1 showed no significant increase in goblet cell density or nuclear-cytoplasmic ratio of conjunctival epithelial cells. (Figure 2a and 2b). The placebo group also showed no significant changes in these two parameters.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis placebo-controlled, randomized, double-masked study examined whether treatment with HPG-HA tear supplements for 3 months alter inflammatory cytokines/chemokines in patients suffering from computer vision syndrome.\u003c/p\u003e\u003cp\u003eThis study found that computer users with symptoms had higher baseline tear cytokine levels. Additionally, using HPG-HA tear supplements did not significantly change inflammatory cytokine or chemokine levels in their tears. After 3 months of intervention, there was improvement in dry eye symptoms, tear production and tear film stability; however, no changes were observed morphologically in conjunctival epithelial cells (nuclear-cytoplasmic ratio) or goblet cell counts.\u003c/p\u003e\u003cp\u003eProlonged computer use is known to cause ocular surface inflammation; this is evidenced by presence of mediators like prostaglandins (PGE2), interleukins (IL-1), and leukotrienes in tears [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Additionally, chronic inflammation of the ocular surface may lead to alteration of epithelial cell morphology and reduction conjunctival goblet cell count [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNumerous artificial tear formulations, differing in composition and viscosity, are available in various forms including gels, ointments, and drops. They help maintain the tear film by supplementing its layers, reducing evaporation, stabilizing it, and lubricating the eyes to prevent complications [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, they do not modify tear cytokines, increase nuclear cytoplasmic ratio (reverse metaplastic changes) in conjunctival epithelial cells, or increase goblet cell counts [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eA study conducted by Duan et al observed decreased mRNA expression of MUC1, MUC16, and MUC20 in the conjunctival impression cytology (CIC) specimens of symptomatic VDT users, compared to VDT users who did not meet the criteria for DED [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Changes in inflammatory cytokines after topical and dietary interventions have not been studied in the tears of symptomatic computer users.\u003c/p\u003e\u003cp\u003eResearch have shown that presence of elevated levels of IL-1, IL-6, IL-8, IFN-γ, and TNF-α in the conjunctival epithelium is linked to dry eye. These studies have primarily concentrated on Sjogren syndrome with aqueous deficient dry eye [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOnly a few studies have documented alteration in cytokines in the tears of people suffering from computer vision syndrome.\u003c/p\u003e\u003cp\u003eA study conducted by Ribelles et al found that older women who work on computers for extended hours exhibit significantly higher levels of IL-1β and IL-6 compared to those who do not engage in computer work [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. This indicated an appropriate inflammatory response in the tears of these patients who frequently use computers. Women taking antioxidants and omega-3 fatty acids showed significantly lower levels of inflammatory cytokines.\u003c/p\u003e\u003cp\u003eA study by Bhargava et al reported that oral administration of anti-inflammatory omega-3 fatty acids can reduce dry eye symptoms, lower tear evaporation rate, and improve Nelson grade in young individuals who use computers for more than 3 hours per day for at least 1 year [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The study suggested that ocular surface inflammation might be a key factor in computer vision syndrome-related dry eye, but did not evaluate tear cytokines and chemokines due to cost constraints.\u003c/p\u003e\u003cp\u003eOur study had limitations and strengths. The patients were not evaluated in controlled conditions; the impact of environmental confounding variables could not be excluded. A randomized controlled study design was our strength. This study is the first to evaluate in inflammatory cytokine expression in computer vision syndrome patients following intervention (Medline Search). Due to cost constraints, not all inflammatory cytokines/chemokines could be analyzed.\u003c/p\u003e\u003cp\u003eIn conclusion, treatment with HPG-HA dual-polymer eyedrops for 3 months did not change tear inflammatory cytokines or increase conjunctival goblet cell density in patients suffering from computer vision syndrome.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eSource of Support\u003c/strong\u003e: Nil\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: We thank \u0026lt;www.indianmedicalstats.com\u0026gt; for statistical analysis\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eJaiswal S, Asper L, Long J, Lee A, Harrison K, Golebiowski B (2019). Ocular and visual discomfort associated with smartphones, tablets and computers: what we do and do not know. Clin Exp Optom. 10:463-477.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHagan S, Lory B (1998). Prevalence of dry eye among computer users. Optom Vis Sci. 75:712-3.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMassingale ML, Li X, Vallabhajosyula M, Chen D, Wei Y, Asbell PA (2009). Analysis of inflammatory cytokines in the tears of dry eye patients. Cornea. 28:1023-7.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCardona G, Argil\u0026eacute;s M, P\u0026eacute;rez-Cabr\u0026eacute; E (2023). Loss of Blink Regularity, and Its Impact on Ocular Surface Exposure. Diagnostics (Basel). 13:2362.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSchlote T, Kadner G, Freudenthaler N (2004). Marked reduction and distinct patterns of eye blinking in patients with moderately dry eyes during video display terminal use. Graefes Arch Clin Exp Ophthalmol 242:306-12.\u003c/li\u003e\n \u003cli\u003eUlhaq ZS, Soraya GV, Budu, Wulandari LR (2020). The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis. Sci Rep. 2020; 10:17453.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCraig JP, Muntz A, Wang MTM, Luensmann D, Tan J, Trave Huarte S, et al (2021). Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial. Ocul Surf. 20:62-69.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBhargava R, Kumar P (2015). Oral omega-3 fatty acid treatment for dry eye in contact lens wearers. Cornea. 34:413-20.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBhargava R, Pandey K, Ranjan S, Mehta B, Malik A (2023). Omega-3 fatty acids supplements for dry eye - Are they effective or ineffective? Indian J Ophthalmol. 71:1619-1625.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBhargava R, Rajpoot M, Arora Y, Sharma SK, Sharma S (2017). Dietary Omega-3 Fatty Acids Supplements for Dry Eye in Psoriasis: Are they Effective? J Clin of Diagn Res.\u0026nbsp;11(11):NC01-NC05.\u003c/li\u003e\n \u003cli\u003eThe definition and classification of dry eye disease (2007): Report of the definition and classification subcommittee of the international dry eye workshop. Ocul Surf 5:75\u0026ndash;92.\u003c/li\u003e\n \u003cli\u003eApostol S, Filip M, Dragne C, Filip A (2003). Dry eye syndrome. Etiological and therapeutic aspects. Oftalmologia. 2003; 59:28-31.\u003c/li\u003e\n \u003cli\u003eJones L, Downie LE, Korb D, Dana R, Deng S, Dong P, et al (2017). TFOS DEWS II Management and Therapy Report. \u003cem\u003eOcul Surf\u003c/em\u003e 15:575\u0026ndash;628.\u003c/li\u003e\n \u003cli\u003ePucker AD, Ng SM, Nichols JJ (2016). Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev :CD009729.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKumar P, Bhargava R, Kumar M, Ranjan S, Kumar M, Verma P (2014). The correlation of routine tear function tests and conjunctival impression cytology in dry eye syndrome. Korean J Ophthalmol 28:122\u0026ndash;129.\u003c/li\u003e\n \u003cli\u003eMaity M, Galor A, Basu S, Singh S (2024). Tear Film Dynamics in Visual Display Terminal Users: A Review of Impact on Goblet Cells, Lacrimal and Meibomian Gland Function. Semin Ophthalmol:1-14.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDuan H, Yang T, Zhou Y, Ma B, Zhao L, Chen J, Qi H (2023). Comparison of mucin levels at the ocular surface of visual display terminal users with and without dry eye disease. BMC Ophthalmol. 23:189.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMassingale ML, Li X, Vallabhajosyula M, Chen D, Wei Y, Asbell PA (2009). Analysis of inflammatory cytokines in the tears of dry eye patients. Cornea.28(9):1023-7.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePflugfelder SC, Jones D, Ji Z, Afonso A, Monroy D (1999). Altered cytokine balance in the tear fluid and conjunctiva of patients with Sj\u0026ouml;gren\u0026apos;s syndrome keratoconjunctivitis sicca. Curr Eye Res 19:201-11.\u003c/li\u003e\n \u003cli\u003eSolomon A, Dursun D, Liu Z, Xie Y, Macri A, Pflugfelder SC (2001). Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease. Invest Ophthalmol Vis Sci.42:2283-92.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRibelles A, Galbis-Estrada C, Parras MA, Vivar-Llopis B, Marco-Ram\u0026iacute;rez C, Diaz-Llopis M (2015). Ocular Surface and Tear Film Changes in Older Women Working with Computers. Biomed Res Int. 2015:467039.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBhargava R, Kumar P, Phogat H, Kaur A, Kumar M (2015). Oral omega-3 fatty acids treatment in computer vision syndrome related dry eye. Cont Lens Anterior Eye 38:206-10.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eKey characteristics\u0026nbsp;(baseline)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e*Measure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 1(tear supplement)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 2 (Placebo)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u003cstrong\u003et-test P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e23.1\u0026plusmn;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e23.8\u0026plusmn;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eIL1\u0026beta;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e523\u0026plusmn;47.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e522.3\u0026plusmn;47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.943\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eIL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e131.6\u0026plusmn;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e134\u0026plusmn;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eIL4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e364.6\u0026plusmn;7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e366.4\u0026plusmn;18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eIL5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e264.8\u0026plusmn;13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e266.3\u0026plusmn;14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eIL6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e1404\u0026plusmn;4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e1400\u0026plusmn;4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eIL8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e473\u0026plusmn;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e474.8\u0026plusmn;34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.069\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eIL10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e452\u0026plusmn;13.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e458\u0026plusmn;44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.146\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eIF \u0026gamma;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e320\u0026plusmn;16.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e322\u0026plusmn;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.666\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eTNF\u0026alpha;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e344\u0026plusmn;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e346\u0026plusmn;44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.234\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eDESS Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e7.6\u0026plusmn;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e7.4\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.539\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eSchirmer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e17.3\u0026plusmn;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e17.5\u0026plusmn;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.548\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eTBUT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e11.8\u0026plusmn;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e12.1\u0026plusmn;2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.467\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNelson Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e1.2\u0026plusmn;0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e1.25\u0026plusmn;0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.303\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eGCD (cells/mm2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e780\u0026plusmn;21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e783\u0026plusmn;20.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.344\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe data is presented as mean \u0026plusmn; standard deviation, TBUT (tear film break up time) and GCD (Goblet cell density, cells/mm\u0026sup2;).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eGroup 1 mean test values at 6 months post-intervention\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e*Measure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6 months post intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u003cstrong\u003et-test P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eIL1\u0026beta;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e523\u0026plusmn;47.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e518\u0026plusmn;51.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.632\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eIL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e131.6\u0026plusmn;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e129\u0026plusmn;5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.093\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eIL4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e364.6\u0026plusmn;7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e361\u0026plusmn;11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.173\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eIL5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e264.8\u0026plusmn;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e262\u0026plusmn;9.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.105\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eIL6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e1404\u0026plusmn;4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e1401\u0026plusmn;9.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eIL8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e473\u0026plusmn;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e470\u0026plusmn;9.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eIL10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e452\u0026plusmn;13.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e450\u0026plusmn;18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.437\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eIF \u0026gamma;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e320\u0026plusmn;16.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e316\u0026plusmn;16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.266\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eTNF\u0026alpha;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e344\u0026plusmn;8.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e342\u0026plusmn;8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.175\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eDESS Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e7.6\u0026plusmn;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e1.2\u0026plusmn;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eSchirmer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e17.3\u0026plusmn;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e19.9\u0026plusmn;1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eTBUT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e11.8\u0026plusmn;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e15.4\u0026plusmn;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eNelson Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e1.2\u0026plusmn;0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e1.16\u0026plusmn;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.503\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eGCD (cells/mm2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e780\u0026plusmn;21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e774\u0026plusmn;26.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.281\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* The data is presented as mean \u0026plusmn; standard deviation, TBUT (tear film break up time) and GCD (Goblet cell density, cells/mm\u0026sup2;).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. \u003cstrong\u003eMean test values at 3 months after intervention (Group 2)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e*Measure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3 months post intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u003cstrong\u003et-test P value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eIL1\u0026beta;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e522.3\u0026plusmn;47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e524\u0026plusmn;45.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.836\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eIL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e134\u0026plusmn;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e135\u0026plusmn;5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.362\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eIL4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e366.4\u0026plusmn;18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e365\u0026plusmn;5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.526\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eIL5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e266\u0026plusmn;4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e264\u0026plusmn;4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eIL6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1400\u0026plusmn;4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e1399\u0026plusmn;6.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eIL8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e474.8\u0026plusmn;34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e473.5\u0026plusmn;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eIL10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e458\u0026plusmn;4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e456\u0026plusmn;4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.839\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eIF \u0026gamma;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e322\u0026plusmn;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e319\u0026plusmn;14.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.789\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTNF\u0026alpha;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e346\u0026plusmn;4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e344\u0026plusmn;4.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.654\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eDESS Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e7.4\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e5.2\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eSchirmer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e17.5\u0026plusmn;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e17.8\u0026plusmn;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTBUT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e12.1\u0026plusmn;2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e13.8\u0026plusmn;2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eNelson Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.25\u0026plusmn;0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e1.2\u0026plusmn;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.282\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eGCD (cells/mm2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e783\u0026plusmn;20.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003e780\u0026plusmn;21.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* The data is presented as mean \u0026plusmn; standard deviation, TBUT (tear film break up time) and GCD (Goblet cell density, cells/mm\u0026sup2;).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Mean test values at 3 months post-intervention\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e*Parameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 1(tear supplement)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 2 (Placebo)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value (independent t -test)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eIL1\u0026beta;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e518\u0026plusmn;51.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e524\u0026plusmn;45.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.533\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eIL2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e129\u0026plusmn;5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e135\u0026plusmn;5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.131\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eIL4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e361\u0026plusmn;11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e365\u0026plusmn;5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.261\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eIL5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e262\u0026plusmn;9.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e264\u0026plusmn;4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eIL6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1401\u0026plusmn;9.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e1399\u0026plusmn;6.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.238\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eIL8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e470\u0026plusmn;9.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e473.5\u0026plusmn;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.068\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eIL10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e450\u0026plusmn;18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e456\u0026plusmn;4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.090\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eIF \u0026gamma;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e316\u0026plusmn;16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e319\u0026plusmn;14.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.268\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eTNF\u0026alpha;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e342\u0026plusmn;8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e344\u0026plusmn;6.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.136\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eDESS Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e3.8\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e5.2\u0026plusmn;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eSchirmer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e19.9\u0026plusmn;1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e17.8\u0026plusmn;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eTBUT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e15.4\u0026plusmn;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e13.8\u0026plusmn;2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNelson Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e1.16\u0026plusmn;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e1.2\u0026plusmn;0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.242\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eGCD (cells/mm2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e774\u0026plusmn;26.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e780\u0026plusmn;21.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 186px;\"\u003e\n \u003cp\u003e0.099\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Expressed as mean \u0026plusmn; standard deviation, TBUT (tear film break up time), GCD (Goblet cell density (cells/mm2).\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Computer vision syndrome, dry eye, tear cytokines, goblet cell density","lastPublishedDoi":"10.21203/rs.3.rs-6953604/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6953604/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eTo examine the impact of hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer eyedrops on inflammatory cytokines in the tears of individuals experiencing computer vision syndrome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A randomized, double-masked, multi-center interventional study was conducted. One hundred sixteen computer users with symptoms (using computers over 3 hours daily for at least 1 year) were randomized into two groups; 56 patients recei ved HPG-HA eyedrops, and 60 patients received preserved saline drops, both twice daily for duration of 3 months. The primary outcome was the reduction of inflammatory cytokines (IL-1β, IL2, IL4, IL5, IL6, IL8, IL10, IF-γ, TNF-α) in conjunctiva and tears of computer users. Secondary outcomes encompassed alterations in dry eye symptom scores, Schirmer test results, TBUT values, and Nelson grade at the 3-month mark.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: At baseline, tear inflammatory cytokines and tear film parameters were similar in both the supplement and placebo groups. Tear inflammatory cytokine levels showed no significant changes from baseline at three months post-intervention in the tear supplement group, despite numerical reduction. However, the tear supplement group demonstrated a notable improvement in dry eye symptoms (P \u0026lt; 0.001), Schirmer test scores (P \u0026lt; 0.001), and TBUT scores (P \u0026lt; 0.001); however, there was no significant alteration in goblet cell counts or morphology og conjunctival epithelial cells.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Treatment with hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer eyedrops for 3 months does alleviates dry eye symptoms and decreases tear evaporation rate in patients with computer vision syndrome. However, it does not alter tear inflammatory cytokines nor increase conjunctival goblet cell density.\u003c/p\u003e","manuscriptTitle":"The effect of hydroxypropyl guar-hyaluronic acid (HPG-HA) dual-polymer eyedrops on inflammatory cytokine expression in tears of patients with computer vision syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-22 10:20:01","doi":"10.21203/rs.3.rs-6953604/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4f260fff-9eb6-4bc9-9616-208cc776376c","owner":[],"postedDate":"September 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-24T07:54:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-22 10:20:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6953604","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6953604","identity":"rs-6953604","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}