Cheng-Wei Lin1†
I-Chan Lin- 1School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- 2Department of Ophthalmology, Taipei Medical University, Shuang Ho Hospital, New Taipei City, Taiwan
- 3Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- 4Department of Ophthalmology, Hualien Tzu Chi Hospital, Hualien, Taiwan
- 5Department of Ophthalmology, Taipei Medical University Hospital, Taipei, Taiwan
- 6Department of Ophthalmology, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan
Dry eye disease (DED) is a common multifactorial disease affecting a substantial proportion of the population worldwide. Objective tests and subjective symptoms evaluation are necessary to assess DED. Although various treatments have been introduced, accurately evaluating the efficacy of those treatments is difficult because of the disparity between diagnostic tests and patient-reported symptoms. We reviewed the questionnaires used to evaluate DED and the improvements of quality of life with various treatments. In addition, we highlighted the importance of patient-reported outcomes (PRO) assessments for evaluating the effect of DED treatments. Given that the assessment of DED treatment effectiveness substantially relies on individual ocular experiences, acquiring qualitative PRO data is essential for comprehensive evaluation and optimal treatment management. Clinicians should not only focus on improving objective symptoms but also prioritize the well-being of patients in clinical management.
Introduction
Dry eye disease (DED) is a common ocular surface disease that affects a substantial proportion of the population worldwide. The prevalence of DED varies across different regions, ranging from 4.6% in North America to 47.9% in Africa (1). In Asian countries, approximately 20.1% of individuals develop DED (2). Moreover, in some industrialized Asian countries, such as Taiwan (3), Korea (4), and Japan (5), over a quarter of the population is affected.
DED is a multifactorial disease characterized by an imbalance between insufficient aqueous production (6) and excessive tear evaporation (7). Decreased tear production by the lacrimal gland results in less eye surface lubrication, and decreased oil secretion by the meibomian gland leads to excessive tear evaporation (8). The decreased wettability type of DED is characterized by a short tear film break-up time (TBUT), normal tear production, and minimal or no staining. This type results from the deficiency or abnormality of membrane-associated mucin, causing impaired corneal surface wettability (9). The most common risk factors with the strongest contribution for DED include female sex, contact lens usage, prolonged computer use, thyroid abnormalities, hypertension, antidepressant use, and antihistamine use (2). Other risk factors include Asian ethnicity (10), hormonal dysfunction and replacement therapy (11), Sjögren’s syndrome (12, 13), lifestyle factors (14), aging (2, 15, 16), medication usage, and cataract surgery (17, 18). These factors contribute to tear film instability, hyperosmolarity, ocular surface inflammation, and subsequent ocular discomfort (19).
Previously, DED was mainly attributed to aqueous insufficiency and ocular surface inflammation. Recent research has indicated meibomian gland dysfunction (MGD) as the leading cause of DED, particularly evaporative DED, and aqueous-deficient dry eye may be caused by MGD (5, 7). Thus, new diagnostic assessments and therapeutic interventions have been developed to address MGD (5, 20, 21) and restore the homeostasis of the tear film.
Objective tests and subjective symptom examination are mandatory for the accurate diagnosis of DED. However, disparities between diagnostic tests and patient-reported symptoms have been reported because of varied etiologies and clinical presentations (22–24). By evaluating patients’ symptoms and quality of life (QoL), the effect of the disease on individuals can be determined. Currently, no single test is available that can precisely predict and evaluate an individual’s response to treatment. Therefore, a standardized classification system that combines objective measurements with subjective symptom assessment and functional lifestyle evaluation through the use of well-designed questionnaires has been recommended to guide treatment strategies (19, 24, 25).
Various questionnaires have been developed to examine patient-reported outcomes (PROs) and the subjective symptoms of DED. Herein, we review the efficacy of conventional and advanced therapies as well as procedures (punctual occlusion, thermal pulsation, and intense pulsed light) in alleviating clinical signs and patient-reported symptoms. In addition, we evaluated questionnaires used to examine subjective ocular symptoms and QoL.
In this review, we evaluated the literature on the effect of current DED treatments on subjective outcomes. Given that subjective symptoms do not consistently correlate with objective clinical advancements, we focused on investigating the effects of treatments on the basis of patients’ self-reported improvements, encompassing self-reported symptoms, and satisfaction levels and by using validated questionnaires. By examining patients’ subjective responses to various treatment modalities, we intended to provide practitioners with valuable references for making informed treatment decisions. In our data search for clinical-trial-based articles, we initially employed specific commercial products or ingredients as primary search terms. Subsequently, we complemented our search by including the terms “dry eye” and “subjective” to refine and identify targeted search results. We comprehensively searched reputable databases, such as PubMed, Medline, and Web of Science, for relevant published studies related to DED treatments and their subjective impact. All articles meeting our search criteria that were published between 2000 and November 2022 (n = 9,050) were meticulously analyzed to identify clinical-trial-based publications focusing on assessment of QoL and subjective outcomes in human (in vivo) studies. With careful consideration, relevant articles investigating DED treatments and subjective assessments were selected, and their full contents were thoroughly evaluated (n = 255). The subsequent sections elucidate specific treatments for DED, including a detailed evaluation of their effects on QoL and patient satisfaction. We included not only original research papers but also other types of papers, such as trials and reviews, examining treatments for DED and questionnaires used to evaluate the QoL of patients with DED. We review studies on questionnaires and assessment tools for DED, and discuss the treatment options for DED. In addition, we discuss the advantages and disadvantages of possible treatment options for DED through comparative analysis.
Review on DED treatments and subjective assessments
Questionnaires and assessment tools for DED and ocular symptoms
PROs are highly valuable references because they directly capture the patient’s perspective without any interpretation from clinicians or third parties (26). Quantitative measurements alone may not always provide a definitive diagnosis of DED (27). Therefore, well-designed PRO instruments can provide complementary information and a more comprehensive understanding of patients’ condition (28). In addition to investigating the effect of DED or the effectiveness of its treatment, evaluating treatment satisfaction on the basis of direct patient feedback is essential. This evaluation can determine the effectiveness of treatment in alleviating symptoms as well as its convenience and accessibility.
Our review revealed various questionnaires and assessment tools that have been employed to differentiate patients with DED from those with normal ocular health and to capture subjective treatment outcomes. We categorized these questionnaires into two groups on the basis of their intended purpose: subjective ocular symptom measurement and QoL assessment. Because both groups of questionnaires rely on the subjective responses of individual patients, we compiled a table to differentiate the characteristics and purposes of each questionnaire (Table 1).
Table 1. Questionnaires and assessment tools for DED and ocular symptoms.
DED treatments
AT and ointments are commonly used as first-line therapy 1 (55, 56). They are available in various formulations with different active ingredients, electrolyte compositions, osmolarity, and viscosities (57). These formulations may contain viscosity-enhancing agents, electrolytes, osmoprotectants, oily compounds, antioxidants, and preservatives. Oily agents and surfactants supplement the tear film lipid layer. Antioxidants, such as vitamin A and vitamin E, are integrated to address oxidative stress associated with DED (58, 59).
Tear supplements: active ingredients
Polymeric composites are commonly incorporated into artificial tears due to their hygroscopic and mucoadhesive properties. One advantage is the enhancement of tear viscosity, which prolongs the duration of tear retention on the ocular surface and maintains smooth tear distribution (60). Among the listed ophthalmic demulcents, carbomer, also known as polyacrylic acid, is an earlier additive used to increase the viscosity of artificial tears; its capacity to prolong ocular hydration has been reported (61). Enhancing the tear remnant improves TBUT and fluorescein test results, reduces subjective symptoms (62, 63), and improves patients’ QoL (64, 65). Since then, polymeric composites have been used to alleviate the symptoms of DED (Table 2).
Table 2. Tear supplement: active ingredients.
Osmoprotectants
The hyperosmolarity of the tear film enhances inflammatory responses, leading to the morphological damage of ocular surface cells such as apoptosis of cells of the conjunctiva and cornea. The hyperosmolarity also triggers inflammatory cascades that contribute to further cell death, including loss of mucin-producing goblet cells. These reactions exacerbate DED symptoms (112). Conventional methods for addressing hyperosmolarity in DED involve the use of hypotonic tear substitutes, which exhibit a relatively brief duration for 1-2 minutes. Recently, new formulations of artificial tears have been created, incorporating one or more osmoprotectants. Table 3 contains the types of osmoprotectants that have been utilized.
Table 3. Types of osmoprotectants (OsPrs).
Topical secretagogues
Topical immunomodulators
Topical immunomodulators have been used because of their ability to disrupt the inflammation pathway (Table 4) (140). Although topical corticosteroids can effectively disrupt the inflammatory and immune response cycle of DED, their long-term use can cause complications, such as ocular hypertension and opportunistic infections (141, 142). Tetracyclines are broad-spectrum antibiotics that possess anti-inflammatory properties. They are occasionally prescribed to treat disorders associated with DED. However, the long-term risks and safety of their use are still not well understood (141). Table 5 lists the effective topical immunomodulators, which had been applied clinically.
Table 4. Topical secretagogues.
Table 5. Topical immunomodulators.
Biological tear substitutes
Blood-derived topical products were first used to treat ocular surface disease by Ralph et al. in 1979 (159). Since then, serum eye tears have been used to treat DED in clinical practice (Table 6).
Table 6. Biological tear substitutes.
Nutritional intervention
Previous studies have explored the use of nutritional strategies to improve DED. A novel botanical combination of lutein ester; zeaxanthin; and extracts from blackcurrant, chrysanthemum, and goji berry was designed to treat adults with eye fatigue. This formula ameliorated eye soreness, blurred vision, dry eye, foreign body sensation, and increased tearing, resulting in enhanced scores on questionnaires used to evaluate dry eye conditions (178).
Procedures
Punctal occlusion can reduce the drainage of tears into the lacrimal ducts, thereby conserving tears, providing lubrication, and alleviating dry eye symptoms (179). Many types of plugs, including those made of silicone and collagen, have been investigated. Improvements in irritative symptoms, as well as reductions in central, superior, nasal, and temporal corneal staining were noted DED patients with bilateral punctal plug insertion (Table 7).
Table 7. Procedure options for DED.
Botulinum toxin type A injection in the medial part of the lower eyelid is considered an alternative method of punctal occlusion to reduce lacrimal drainage (239). Botulin toxin type-A (BTX-A) can demonstrate less lacrimal clearance by denervating lacrimal part of orbicularis oculi muscle. This procedure can be done by injecting BTX-A into upper or lower eyelids. Injection in the lower eyelid alone showed better improvements than injection in both the upper and lower eyelids. However, the effect cannot last long in most patient with a range of 3 months (240).
Vector thermal pulsation (VTP) can provide warm compress to the eyelids and meibomian gland (241). Thermal pulsation has many advantages, with potentially the longest-lasting per-treatment effect for MGD (206). Intense pulsed lighting involves the application of highly intensified pulses of polychromatic light across a broad wavelength range (515–1,200 nm) for eliminating superficial capillary vessels in the periocular region, reducing the release of tear inflammatory cytokines, and improving the outflow of the meibomian gland (211). However, because of the paucity of high-quality research, the effectiveness and safety of long-term intense pulsed lighting treatment for MGD remain uncertain, necessitating further research (242).
Salivary gland transplantation should be considered to treat severe DED. Submandibular gland transplantation (SMGT) and minor salivary gland transplantation (MSGT) are the most commonly used procedure, while parotid gland was proved to be non-beneficial for severe DED (227, 228). Previous studies demonstrated autologous microvascular SMGT improved objective signs and subjective symptoms of severe DED (229, 230, 243). Su et al. conducted a prospective study and revealed that the significant improvement of life quality and satisfaction of DED patients after SMGT (231). Although SMGT and MSGT provided benefits for severe DED patients, SMGT should be recommended to treat end-stage refractory DED (232). Table 8 compiles a summary of various treatment options for DED, encompassing tear supplements, osmoprotectants, secretagogues, immunomodulators, biological tear substitutes, and procedures.
Table 8. Treatment options for DED.
Conclusion
In our investigation of various treatments and questionnaires for DED, we found multiple validated questionnaires designed to collect PROs. Although inconsistencies exist between questionnaires and clinical findings, they provide valuable information in the initial evaluation and monitoring of DED treatments. However, the lack of standardized measures and intergroup conversion causes difficulty in cross-comparison.
The initial therapy of DED involves the use of artificial tears. Over-the-counter formulations containing ingredients, such as CMC and HA, and osmoprotectants, such as trehalose, aim to restore hydration and lubrication, thereby alleviating dry eye symptoms (69, 244). However, in advanced cases of moderate-to-severe dry eyes, artificial tears might not be effective (245). Liposomal tear drops are beneficial for both evaporative and non-evaporative DED (94), and secretagogue drops can improve the QoL of patients with short TBUT or aqueous deficient-type DED (113).
Immunomodulators provide rapid symptom relief, and most patients with DED report the effectiveness and high satisfaction rate of cyclosporine A (CsA) and lifitegrast (246–248). However, trials have consistently reported adverse events, such as irritation or pain at the instillation site, which may affect patient compliance and therapy efficacy (249, 250).
Patients who received autologous serum (AS) treatments reported high satisfaction and expressed eagerness to continue the therapy (251). However, well-established production and storage protocols are still needed for their clinical use (160, 161). Punctual occlusion has been performed to either temporarily or permanently block tear drainage from the lacrimal punctum. However, this procedure is associated with a higher complication rate (even up to 60%) (252), making it a less favorable option for treating DED (239). BTX-A serving as a temporary solution for DED, it can significantly improve symptoms within 3 months by reducing lacrimal drainage (240).
VTP is a novel therapy option, particularly for DED caused by MGD (195, 253). VTP offers a convenient solution for individuals with MGD-related dry eye, representing an alternative treatment option for patients with modern busy lifestyles (254). Intense pulsed light(IPL) also has proven to be effective for treating evaporative dry eye caused by MGD (255), with 93% of patients reporting posttreatment satisfaction without any severe adverse effects. Multiple studies have confirmed the efficacy of combining IPL treatment with meibomian gland manipulation (256).
In severe DED cases, SMGT offers a promising approach for tear film restoration (243). Previous studies demonstrated autologous SMGT has a high success rate, and it significantly improved quality of life and satisfaction (231).
Overall, patient satisfaction and QoL evaluations often improved after different DED treatment modalities. This review highlights the importance of PRO assessments for evaluating the effect of DED treatments on subjective symptoms and QoL. Given that the assessment of DED treatment effectiveness substantially relies on individual ocular experiences, acquiring qualitative PRO data is essential for comprehensive evaluation and optimal treatment management. Clinicians should not only focus on improving objective symptoms but also prioritize the well-being of patients in clinical settings.
Author contributions
C-WL: Investigation, Writing – original draft. M-YL: Conceptualization, Formal analysis, Supervision, Visualization, Writing – review & editing. J-WH: Conceptualization, Formal analysis, Methodology, Resources, Writing – review & editing. T-JW: Writing – original draft, Investigation, Methodology, Project administration, Visualization. I-CL: Methodology, Supervision, Writing – review & editing.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported in part by a grant from Taipei Medical University (TMU112-AE1-B04).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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Keywords: dry eye diseases, quality of life, patient-reported outcomes, treatment, impact
Citation: Lin C-W, Lin M-Y, Huang J-W, Wang T-J and Lin I-C (2024) Impact of dry eye disease treatment on patient quality of life. Front. Med. 11:1305579. doi: 10.3389/fmed.2024.1305579
Edited by:
Yonathan Garfias, National Autonomous University of Mexico, MexicoReviewed by:
Angel Nava-Castañeda, Instituto de Oftalmología Fundación de Asistencia Privada Conde de Valenciana, IAP, MexicoGuang-yan Yu, Peking University Hospital of Stomatology, China
Copyright © 2024 Lin, Lin, Huang, Wang and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: I-Chan Lin, aWNoYW5saW5AZ21haWwuY29t
†These authors have contributed equally to this work