Dry eye symptoms and impact on vision-related function across International Task Force guidelines severity levels in the United States

Dry eye is a multifactorial disease of the ocular surface resulting in discomfort, visual disturbance, and instability of the tear film [1]. In the early 2000s, it was estimated that dry eye affected over 7 million people over the age of 40 years in the United States [2, 3]. Prevalence has likely increased significantly over the past 10 years with the escalation of risk factors such as an aging population, a greater number of refractive laser surgeries, and more frequent use of contact lenses, computers, smartphones, and tablets [2–5]. Additionally, women are known to experience dry eye more frequently than men, potentially owing to hormone fluctuations during the menstrual cycle or menopause, and from use of oral contraceptives or hormone replacement therapy [6].

The symptoms that commonly compel patients with dry eye to seek treatment from ophthalmologists and optometrists include ocular discomfort and irritation, burning, itching, and blurred vision [7, 8]. In addition to blurring of vision, other changes in visual function noted in dry eye patients include reductions in functional visual acuity [9] and contrast sensitivity [10], optical aberration due to tear film irregularity [11], and degradation of retinal image quality [12]. Dry eye disease significantly affects patients’ visual function and greatly impacts social and physical functioning, workplace productivity, and quality of life [13, 14]. For example, ocular discomfort and dryness are often reported as the primary reason for discontinuation of contact lens wear [15–18], negatively affecting patients’ quality of life. In one study conducted in the United Kingdom using utility assessment (Time Trade-Off and Standard Gamble methods) to quantify and understand the impact of a given health condition relative to other diseases, severe dry eye utilities were similar to those associated with dialysis or severe angina [19].

Symptomatic dry eye disease can present without evidence of ocular surface damage or changes in tear flow [13, 14, 20]. Poor correlation has been found between symptoms and clinical measures of dry eye disease [21–24], and patient-reported dry eye symptoms have been demonstrated to be more reproducible from visit to visit than many of the clinical signs used to diagnose and monitor dry eye [25]. Consequently, quality of life or patient-reported outcomes (PRO) evaluations have been used to provide clinicians with valuable information on the impact of dry eye disease and the effectiveness of treatment [26, 27]. The Ocular Surface Disease Index (OSDI) is a validated PRO instrument that provides a measure of the ocular symptoms and disability associated with dry eye [20, 28]. The OSDI was developed as a brief, self-administered questionnaire to provide rapid evaluation of the range and frequency of ocular symptoms associated with dry eye disease, and their impact on patients’ visual functioning. The questionnaire includes 3 subscales, which cover ocular discomfort, limitations in performance of daily activities affected by dry eye, and the susceptibility of dry eye symptoms to environmental factors. As an instrument, OSDI shows internal consistency, with good to excellent test-retest reliability and excellent discriminant validity for measuring dry eye symptoms [28].

The International Task Force (ITF) guidelines for diagnosis and treatment of dry eye were established by an expert panel that considered dry eye disease severity to be the most important factor in making treatment decisions [29]. The ITF panel established a 4-level dry eye severity grading scheme based on signs and symptoms [29]. A study evaluating the implementation of this scheme by clinicians found these guidelines to be simple and efficient for assessing dry eye severity and for supporting treatment decisions [30]. Notably, use of the ITF guidelines led clinicians to focus on patient symptoms and initiating early treatment rather than relying on dry eye diagnostic tests [30].

As standard clinical measures of dry eye provide only a partial picture of the disease experience, it is difficult to appreciate how dry eye is perceived by the patient. The current study was conducted to quantify the frequency of dry eye symptoms and their impact on vision-dependent functioning across different ITF levels, using the OSDI questionnaire. Patients were prescription treatment-naïve (received no prescription therapy for dry eye disease) presenting to their clinicians with complaints of dry eye. Although studies have assessed symptoms in patients with dry eye [7, 13, 14, 20], to date no real-world, clinic-based studies assessing dry eye symptoms and the impact of disease based on ITF severity categories have been reported in the published literature.

Variation in diagnostic criteria and clinical measures of dry eye disease and its severity have been reported [25], and poor correlation between clinical signs and patient-reported symptoms has been documented in previously published literature [21–23]. Discordance between ocular surface findings and symptoms of dry eye may occur in the early stages of disease where symptoms can exist without clinical signs of dry eye [32]. Some investigators have hypothesized that chronic dry eye symptoms occurring in the absence of clinical signs of dry eye might be of neuropathic origin, arising as a result of central sensitization and manifesting as neuropathic ocular pain [33, 34]. The ITF guidelines were developed from expert consensus to establish severity criteria and treatment recommendations for dry eye [29], and formed a foundation for the 2007 International Dry Eye Workshop management and therapy of dry eye guidelines [35]. To date, there are no studies that have evaluated the impact of disease, in particular its functional impact, in prescription-naïve dry eye patients across ITF severity levels in a real-world, clinic-based setting.

In this observational study of patients with symptomatic dry eye, no significant overall differences were observed in patient demographics, concomitant non-dry eye-related ocular conditions, and comorbidities (other than hypertension) across the 3 dry eye patient cohorts based on ITF severity level (ITF level 1, ITF level 2, and ITF level 3/4 combined). Almost one-third of the patients enrolled in the study had cataracts and less than 10% had glaucoma. Very few (3%) patients enrolled in this study had Sjögren’s syndrome, an autoimmune condition associated with severe dry eye. Of the 30 patients enrolled who presented with central corneal staining, 29 were in ITF severity level 3/4. This, together with the higher prevalence of cataract in ITF severity level 3/4, may have contributed to the greater proportion (≥2 times) of patients in the ITF level 3/4 cohort who reported poorer visual acuity (20/40 to 20/60+) in both eyes compared with the lower ITF severity level 1 and 2 cohorts.

The study demonstrated that all OSDI subscale scores, including those for Visual Function and Environmental Triggers, were significantly worse in higher ITF severity level cohorts. This would indicate that the observed deterioration in OSDI overall score with increasing ITF severity was not driven solely by worsening dry eye symptoms. Pairwise tests demonstrated that overall and subscale domain OSDI scores were significantly higher in the ITF level 3/4 cohort compared with ITF level 1 and ITF level 2 cohorts, except for the Environmental Triggers domain score, which was not significantly different between ITF level 3/4 and ITF level 2 cohorts. In addition, analysis of individual OSDI questions demonstrated that a higher percentage of ITF level 3/4 patients experienced not only more frequent symptoms of dry eye, but also more frequent disruption of daily tasks and more frequent symptoms from environmental triggers of dry eye. Assessed against the published OSDI guideline categories of mild (13–22), moderate (23–32), and severe (≥33) ocular surface disease [31], patients in this study generally had frequent ocular disability, as reflected in overall mean OSDI scores of 26.5, 33.8, and 44.9 in ITF level 1, 2, and 3/4 cohorts, respectively, although intracohort variation in overall OSDI score was appreciable (based on standard deviation values in Table 3). Observed differences from the published guidelines may be associated with a different anchor (such as Global Clinician’s Assessment versus ITF guidelines) that was used to establish disease severity [31].

Our study results, obtained from a sample of prescription treatment-naïve patients presenting with symptomatic dry eye in the real-world setting, are consistent with previously reported clinical study findings that OSDI overall scores increase as levels of dry eye severity worsen. In a study by Schiffman et al. [28], patients’ severity of dry eye was categorized using 2 evaluations: physician assessment and a composite score that combined traditional clinical measures (Schirmer’s test and lissamine green staining) and a symptoms-based measure (patients’ perception of ocular symptoms, as assessed using the McMonnies Dry Eye Questionnaire [36] and the National Eye Institute Visual Functioning Questionnaire [NEI VFQ-25] [37]). Overall mean OSDI scores grouped into “normal”, “mild/moderate”, and “severe” categories were 9.6, 20.8, and 36.3 based on physician assessment, respectively, and 4.5, 18.1, and 36.3 based on patients’ composite score, respectively [28]. In another study by Sullivan et al. [38], a composite score of dry eye severity was established by converting clinical measures (tear osmolarity, Schirmer’s test, TBUT, Meibomian score, corneal and conjunctival staining) and symptoms (from the OSDI) into a common unit system, whereby 0 represented least evidence of the disease and 1 represented most evidence of disease. Based on the composite score, overall mean OSDI scores in patient groups categorized as having “normal”, “mild/moderate”, or “severe” disease were 5.5, 21.0, and 41.2, respectively [38]. Compared with both the Schiffman [28] and Sullivan [38] studies, patients in our study categorized in ITF level 1 had higher overall OSDI scores, and patients in ITF level 2 had similar OSDI scores to patients categorized as having “severe disease” in the study by Schiffman et al. [28]. This suggests that mild-to-moderate dry eye as defined by the ITF guidelines may be associated with a relatively high level of ocular disability compared to other composite signs- and symptoms-based measures of dry eye severity.

Our study is limited by the cross-sectional survey design and lack of patient follow-up. Clinicians were not intentionally masked to patients’ previous dry eye diagnoses and treatments, and hence their assessments of dry eye severity (ITF grading) were subject to possible bias. In addition, no specific method for assessment of conjunctival and corneal staining was stipulated for use at the various study sites, other than clinicians’ standard of care. While the absence of formal grading definitions may have resulted in greater variability, the results are likely to be more reflective of a real-world, clinic-based setting. Despite the inherent variability based on this aspect of the study design, statistical significance was still obtained. On the other hand, as a result of restricting study participation to patients seeking medical consultation for their dry eye symptoms, demonstration of statistical significance may have been facilitated by a selection bias toward homogeneity of the patient sample. Accordingly, the generalizability of our study findings remains to be established using a randomly drawn sample from an unselected dry eye population. Prospective studies with follow-up after initiation of treatment will help further define patients’ perceptions of the impact of dry eye on their overall quality of life.

Dry eye disease is frequently undertreated [32, 39, 40]. Barriers to appropriate treatment include the time required to adequately diagnose and determine appropriate treatment based on the patient’s severity level, the perception by clinicians that the condition has minor impact on patient well-being, the perception by patients that the disease is normal or less important than other conditions that require treatment, lack of understanding of the disease process [41], and a perceived paucity of therapeutic options [42, 43]. Supplemental artificial tears and eyelid hygiene are common treatment modalities for dry eye disease, yet many patients continue to experience significant disruption to their daily lives. Our findings suggest that dry eye symptoms are frequently troublesome to the patient at all levels of disease severity, and require attention and adequate treatment. A complete and comprehensive medical and ocular history conducted by clinicians should help correctly identify patients who may have ambiguous symptoms without clinical signs or vice versa, and allow proper treatment and management of dry eye disease.