European Journal of Cardiovascular Medicine

Dry eye disease (DED) is a chronic, multifactorial condition of the ocular surface characterised by loss of tear film homeostasis, accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.¹ The global prevalence of DED ranges from 5% to over 50% depending on the diagnostic criteria employed, the population studied, and the geographic region, making it one of the most common eye conditions encountered in clinical practice.²

The pathophysiology of DED involves a self-perpetuating vicious cycle of tear film instability, hyperosmolarity, and inflammation. Inflammatory mediators, including pro-inflammatory cytokines and matrix metalloproteinases (MMPs), particularly MMP-9, play a central role in perpetuating ocular surface damage and epithelial barrier disruption.³ MMP-9 has emerged as a useful point-of-care biomarker for detecting underlying inflammation in DED and has been shown to correlate with clinical severity.⁴

Several validated instruments have been developed to grade DED severity. The Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) report in 2017 established a standardised framework for DED diagnosis and severity classification incorporating subjective symptom questionnaires and objective clinical tests.⁵ Among symptom questionnaires, the Ocular Surface Disease Index (OSDI) is widely used and validated for capturing patient-perceived disease severity. It comprises 12 items across three subscales — ocular symptoms, vision-related function, and environmental triggers — generating a score from 0 to 100.⁶

The impact of DED on visual function and health-related quality of life (QoL) is substantial. Studies have documented reductions in reading speed, driving ability, and overall visual acuity, as well as increased rates of anxiety, depression, and work productivity loss.⁷ The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) is a well-validated instrument that captures the functional impact of ocular disease on daily activities and emotional wellbeing.⁸

Despite the known burden of DED, there remains a gap in comprehensive studies from South Asian populations examining the relationship between multi-parameter clinical severity scores and patient-reported QoL outcomes across the DED severity spectrum. Many prior studies have relied on single clinical measures or have not simultaneously evaluated objective tear film parameters alongside inflammatory biomarkers and QoL instruments.⁹

Meibomian gland dysfunction (MGD) is the most prevalent form of evaporative dry eye and contributes significantly to tear film lipid layer deficiency. The prevalence of MGD increases with age and is exacerbated by digital screen use, contact lens wear, and systemic diseases such as Sjogren's syndrome and rheumatoid arthritis.¹⁰ Understanding how MGD prevalence changes across severity grades is important for tailoring treatment strategies.

Identifying the degree to which DED severity — as measured by a battery of clinical and patient-reported tools — impairs QoL is essential for clinical decision-making, resource allocation, and health economics research. The present study was therefore conducted to systematically characterise DED severity across mild, moderate, and severe grades in a tertiary ophthalmology centre in India, using both objective parameters and patient-reported outcomes, and to quantify the correlation between clinical severity and QoL.¹¹

2.1 Study Design and Setting This was a hospital-based, cross-sectional, observational study conducted at the outpatient ophthalmology department of a tertiary care centre in Hyderabad, India, over a period of 18 months (January 2018 to June 2019). Institutional ethics committee approval was obtained and all procedures adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants. 2.2 Study Population A total of 200 patients aged 18 years or older with a confirmed diagnosis of DED based on TFOS DEWS II criteria were enrolled. Exclusion criteria included: active ocular infection or inflammation unrelated to DED, prior ocular surgery within 12 months, use of systemic medications known to affect tear production (e.g., antihistamines, antidepressants) within three months, contact lens use on the day of examination, pregnancy, and inability to complete questionnaires due to cognitive or language barriers. 2.3 Clinical Severity Assessment DED severity grading was performed using four standardised clinical parameters. Tear film break-up time (TBUT) was measured as the average of three consecutive measurements using fluorescein strips; values <5s, 5–10s, and >10s corresponded to severe, moderate, and mild instability, respectively. Schirmer's test without anaesthesia (5-minute strip wetting: <5mm severe, 5–10mm moderate, >10mm mild) was used to assess aqueous production. Corneal fluorescein staining was graded on the National Eye Institute (NEI) scale (0–15). Meibomian gland function was evaluated using the meibum quality and expressibility grading system. Tear MMP-9 was measured using a validated lateral flow immunoassay (InflammaDry; Quidel Corporation) and quantified in ng/mL. 2.4 Patient-Reported Outcome Measures The OSDI questionnaire was administered to assess symptom severity (score 0–100; mild: 13–22, moderate: 23–32, severe: ≥33). The NEI-VFQ-25 was used to assess vision-related QoL across seven domains: general vision, ocular pain, near activities, distance activities, social functioning, mental health, and role difficulties. Each domain scored 0–100; higher scores indicate better function. 2.5 Statistical Analysis Patients were stratified into mild (n=62), moderate (n=78), and severe (n=60) DED groups based on composite clinical criteria. Descriptive statistics (mean ± SD, frequency, percentage) were computed for all variables. One-way ANOVA with post-hoc Tukey HSD test was used to compare continuous variables across groups. Pearson correlation coefficients were calculated between key clinical parameters and QoL scores. A p-value of <0.05 was considered statistically significant. All analyses were performed using SPSS version 26 (IBM Corp.).

3.1 Demographic Characteristics (Table 1)

A total of 200 participants were enrolled: 62 with mild, 78 with moderate, and 60 with severe DED. The mean age was highest in the severe group (51.3 ± 13.5 years) compared to mild (38.4 ± 11.2 years) and moderate (44.7 ± 12.8 years) groups, reflecting an age-related increase in disease severity. Females comprised approximately 67–70% across all groups. Duration of symptoms increased markedly with severity (mild: 8.3 ± 4.1 months; severe: 34.2 ± 11.8 months). Systemic comorbidities and meibomian gland dysfunction were most prevalent in the severe group.

Table 1: Demographic and baseline characteristics across DED severity groups.

SD = Standard deviation; DED = Dry eye disease

3.2 Clinical Parameters by Severity Group (Table 2)

All objective clinical parameters showed a significant stepwise worsening with increasing severity (p<0.001 for all). TBUT decreased from 9.2 ± 1.8 s in the mild group to 2.9 ± 0.9 s in the severe group. Schirmer's test values similarly declined from 12.4 ± 3.2 mm to 3.6 ± 1.4 mm. Corneal staining scores escalated from 1.2 ± 0.6 (mild) to 8.6 ± 1.9 (severe). MMP-9 levels rose from 18.3 ± 6.4 ng/mL to 67.4 ± 14.8 ng/mL, confirming progressive inflammation. OSDI scores correspondingly climbed from 18.4 ± 5.2 to 68.9 ± 11.4. Meibomian gland dysfunction was present in only 19.4% of mild patients compared to 78.3% of severe patients.

Table 2: Clinical severity parameters across DED groups (mean ± SD).

TBUT = Tear film break-up time; OSDI = Ocular Surface Disease Index; NEI = National Eye Institute; MMP-9 = Matrix metalloproteinase-9

3.3 Quality of Life Outcomes (Table 3)

NEI-VFQ-25 scores declined progressively across all seven domains as DED severity increased. The composite QoL score fell from 78.0 ± 8.1 in mild DED to 59.6 ± 9.7 in moderate and 40.4 ± 11.2 in severe DED (p<0.001). Ocular pain and mental health subscales were most severely affected, with severe DED patients recording scores of 31.8 ± 10.4 and 36.2 ± 13.4 respectively, reflecting significant pain burden and psychosocial impact. Social function and distance activities were relatively better preserved but still significantly impaired in severe DED patients.

Table 3: NEI-VFQ-25 domain scores across DED severity groups (mean ± SD; higher scores = better function).

NEI-VFQ-25 = National Eye Institute Visual Function Questionnaire-25; QoL = Quality of life

3.4 Correlation Analysis (Table 4)

Pearson correlation analysis demonstrated strong associations between clinical severity parameters and QoL scores. OSDI score showed the strongest negative correlation with NEI-VFQ-25 composite score (r = -0.81, 95% CI: -0.87 to -0.74, p<0.001). TBUT and Schirmer's test values correlated positively with QoL composite scores (r = +0.74 and +0.68, respectively). MMP-9 level correlated strongly with OSDI score (r = +0.76), confirming the role of inflammation in driving subjective symptom burden. Corneal staining correlated negatively with QoL (r = -0.72), while disease duration showed a moderate positive correlation with OSDI (r = +0.63).

CI = Confidence interval; OSDI = Ocular Surface Disease Index; TBUT = Tear film break-up time; MMP-9 = Matrix metalloproteinase-9; NEI-VFQ-25 = National Eye Institute Visual Function Questionnaire-25

Table 4: Pearson correlation coefficients between clinical parameters and QoL outcomes.

Our study provides a comprehensive multi-parameter characterisation of DED severity and its relationship to QoL in a tertiary care South Asian population. The findings corroborate and extend prior research demonstrating that DED severity — whether measured objectively or through patient-reported outcomes — is strongly associated with diminished visual function and broader health-related QoL.12

The progressive decline in TBUT, Schirmer's values, and the parallel rise in corneal staining and MMP-9 with increasing severity grade is consistent with the pathophysiological model described by the TFOS DEWS II report.5 The stepwise increase in MMP-9 levels across severity groups reinforces the central role of inflammation in DED pathogenesis and highlights its utility as a point-of-care biomarker. Villani et al. previously demonstrated that elevated MMP-9 correlates with clinical severity and helps distinguish between aqueous-deficient and evaporative subtypes.4

The strong negative correlation between OSDI scores and NEI-VFQ-25 composite scores (r = -0.81) observed in this study is aligned with earlier work by Schiffman et al.,6 who demonstrated that the OSDI is a reliable and sensitive measure of DED severity that tracks closely with functional visual impairment. Sullivan et al.7 also showed that DED patients report significant impairments in reading, computer use, and driving, all of which are captured by NEI-VFQ-25 subscales and reflected in our results.

The mental health and ocular pain subscales showed the steepest decline with increasing severity in our cohort, suggesting that psychosocial burden is a prominent but underappreciated dimension of DED. This aligns with studies linking chronic DED to anxiety, depression, and reduced work productivity.13 McDonald et al.9 found that QoL impairment in severe DED was comparable to that seen in moderate angina or dialysis-dependent renal failure, underlining the magnitude of the problem.

Meibomian gland dysfunction, present in 78.3% of our severe DED patients, is the most common subtype globally and is frequently underdiagnosed.10 Its strong association with increasing severity and declining QoL in our cohort reinforces the need for routine meibography and targeted lipid layer therapies, such as intense pulsed light and thermal pulsation, in severe-grade patients.

The finding that symptom duration correlated positively with OSDI score (r = +0.63) is clinically relevant. Patients with prolonged, undertreated DED appear to develop a higher subjective symptom burden, potentially driven by neuropathic sensitisation and central sensitisation mechanisms described by Belmonte et al.14 This argues for early aggressive intervention before symptom chronicity sets in.

Our study has several strengths, including a well-defined population, simultaneous use of multiple validated outcome measures, and inclusion of an inflammatory biomarker. Limitations include the cross-sectional design, which precludes causal inference, the tertiary care setting which may introduce referral bias, and the absence of meibography for structural gland assessment. Future longitudinal studies incorporating treatment intervention arms are warranted to determine whether improvement in clinical severity translates to measurable QoL gains.15

This study demonstrates a clear, progressive, and statistically significant relationship between DED severity — assessed using a comprehensive battery of objective clinical tests and patient-reported outcome measures — and deteriorating visual function and quality of life. Patients with severe DED experience substantial ocular pain, emotional distress, and functional impairment that parallel the decline in tear film parameters and the rise in inflammatory biomarkers such as MMP-9. The strong correlation between OSDI and NEI-VFQ-25 underscores the importance of integrating symptom assessment into routine clinical severity grading. Clinicians should adopt a multi-dimensional approach to DED evaluation that encompasses both objective tear film metrics and validated QoL instruments to guide treatment intensity and monitor therapeutic response. Early detection and staged management aligned with severity grading remain imperative to preventing QoL deterioration in this prevalent and often underestimated chronic ocular condition.

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