Special Issue "Dry Eye Syndrome: New Insights on Epidemiology and Management"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Ophthalmology".

Deadline for manuscript submissions: closed (30 October 2019).

Special Issue Editor

Dr. Anat Galor
Website
Guest Editor
Miami VA, Veterans Affairs Medical Center, Miami, FL, USA; Bascom Palmer Eye Institute, Miller School of Medicine at the University of Miami, Miami, FL, USA
Interests: dry eye disease, dry eye, aqueous tear deficiency, evaporative deficiency, ocular surface inflammation, tear osmolarity, epidemiology
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Special Issue Information

Dear Colleagues,

Dry eye (DE) is a common, multifactorial condition that imparts significant morbidity to patients. The term DE is an umbrella term that incorporates many different disease sub-types including immune related (Sjögrens and Graft versus Host disease), in the setting of skin conditions (rosacea), and due to aging changes of the lacrimal and meibomian glands. Each DE sub-type has its own clinical manifestations, pathophysiology, and treatment algorithms. Overall, DE manifests with a combination of symptoms and/or signs. Symptoms include ocular discomfort and pain, characterized as spontaneous and evoked “dryness”, “burning”, “aching”, to name a few descriptors, and visual complaints, such as poor and fluctuating vision. Signs of DE are diverse and include tear and ocular surface abnormalities. This special issue "Dry Eye Syndrome: New Insights on Epidemiology and Management” will highlight new insights on the various DE sub-types, with a focus on epidemiology, pathophysiology, and new treatment approaches.

Dr. Anat Galor
Guest Editor

Manuscript Submission Information

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Keywords

  • Dry eye
  • Aqueous tear deficiency
  • Evaporative deficiency
  • Epidemiology
  • Pathophysiology
  • Treatment

Published Papers (12 papers)

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Editorial

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Open AccessEditorial
Why Internists Should Care About Dry Eye Disease
J. Clin. Med. 2020, 9(2), 532; https://doi.org/10.3390/jcm9020532 - 15 Feb 2020
Abstract
Dry eye disease (DED) has been diagnosed and managed under the purview of the eye care professional, with internists typically not paying much attention to the condition [...] Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)

Research

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Open AccessArticle
Total Tear IgE Levels Correlate with Allergenic and Irritating Environmental Exposures in Individuals with Dry Eye
J. Clin. Med. 2019, 8(10), 1627; https://doi.org/10.3390/jcm8101627 - 04 Oct 2019
Cited by 1
Abstract
Dry eye (DE) and allergic conjunctivitis may present similarly, and it remains unclear whether some individuals have an underlying allergic component to their DE. To better understand this relationship, we performed a cross-sectional study in 75 individuals with DE symptoms and/or signs. Immunoglobulin [...] Read more.
Dry eye (DE) and allergic conjunctivitis may present similarly, and it remains unclear whether some individuals have an underlying allergic component to their DE. To better understand this relationship, we performed a cross-sectional study in 75 individuals with DE symptoms and/or signs. Immunoglobulin E (IgE) levels in tear samples were quantified and home environmental exposures assessed via standardized survey. Tears were collected by Schirmer strip, and total tear IgE levels were quantified using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using descriptive statistics and linear and logistic regressions. The main outcome measures were total tear IgE levels and their association with environmental exposures. The mean age of the subjects was 66.2 ± 7.8 years. Sixty-two individuals had dry eye symptoms (Dry Eye Questionnaire-5 ≥ 6), and 75 had one or more signs of DE. Detectable total tear IgE levels were observed in 76% of subjects, and 17.3% had high levels (>1 ng/mL). Individuals with exposure to pet(s) (odds ratio (OR) 11.5, p = 0.002) and smoke (OR 38.6, p = 0.008) at home were more likely to have high IgE levels compared to those not exposed. Individuals with tears collected during spring or summer were 3.9 times (p = 0.028) more likely to have high IgE compared to those sampled at other times of year. Subjects born in the US were 3.45 times (p = 0.010) more likely to have high IgE compared to individuals born outside the US. To conclude, a majority of individuals with DE symptoms and/or signs had detectable IgE levels in their tears. High tear IgE levels were correlated with allergy season and exposures in the home linked with allergy. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
Open AccessArticle
Pregabalin Failed to Prevent Dry Eye Symptoms after Laser-Assisted in Situ Keratomileusis (LASIK) in a Randomized Pilot Study
J. Clin. Med. 2019, 8(9), 1355; https://doi.org/10.3390/jcm8091355 - 01 Sep 2019
Cited by 2
Abstract
Purpose: Perioperative pregabalin administration has been found to reduce the risk of persistent pain after a variety of surgical procedures. However, this approach has not been tested in relation to eye surgery. As such, the purpose of this study was to evaluate whether [...] Read more.
Purpose: Perioperative pregabalin administration has been found to reduce the risk of persistent pain after a variety of surgical procedures. However, this approach has not been tested in relation to eye surgery. As such, the purpose of this study was to evaluate whether perioperative pregabalin can reduce the presence of dry eye (DE) symptoms, including eye pain, six months after laser-assisted in situ keratomileusis (LASIK). Methods: Prospective, masked, randomized single-center pilot study. Patients were treated with either pregabalin (oral solution of pregabalin 150 mg twice daily, first dose prior to surgery, continued for a total of 28 doses over 14 days) or placebo solution. The primary outcome was dry eye symptoms as measured by the Dry Eye Questionnaire 5 (DEQ-5). Secondary outcome measures included pain-related eye symptoms. Results: In total, 43 individuals were enrolled in the study and randomized to pregabalin (n = 21) or placebo (n = 22). Of those, 42 individuals completed the final visit after six months of follow-up. Some differences were noted between the two groups at baseline, including a higher frequency of females in the pregabalin group. At 6-months, there were no significant differences in the percentage of patients with DE symptoms (DEQ5 ≥ 6, 57% vs. 33%, p = 0.14), DE symptom severity (DEQ5, 6.6 ± 5.0 vs. 4.5 ± 4.2, p = 0.14), ocular pain intensity (numerical rating scale, 1.10 ± 1.48 vs. 0.38 ± 0.97, p = 0.08), or neuropathic pain complaints (Neuropathic Pain Symptom Inventory-Eye, 2.81 ± 4.07 vs. 3.14 ± 5.85, p = 0.83) between the pregabalin and control groups. Ocular signs were likewise similar between the groups, and of note, did not correlate with DE symptoms. The strongest predictor of DE symptoms six months post-surgery was the presence of DE symptoms prior to surgery. Conclusions: Perioperative pregabalin did not reduce the frequency or severity of DE symptoms at a six month follow-up after LASIK in this small pilot study. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
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Open AccessArticle
Treatment Trends in Dry Eye Disease and Factors Associated with Ophthalmic Follow-up Discontinuation in Japan
J. Clin. Med. 2019, 8(8), 1120; https://doi.org/10.3390/jcm8081120 - 28 Jul 2019
Abstract
Despite the importance of dry eye disease (DED) treatment, the rate of DED treatment discontinuation, especially discontinuation of ophthalmic follow-up, remains unknown. This study aimed to assess the prevalence and risk factors of ophthalmic follow-up discontinuation for DED. A cross-sectional survey of 1030 [...] Read more.
Despite the importance of dry eye disease (DED) treatment, the rate of DED treatment discontinuation, especially discontinuation of ophthalmic follow-up, remains unknown. This study aimed to assess the prevalence and risk factors of ophthalmic follow-up discontinuation for DED. A cross-sectional survey of 1030 participants was conducted using a self-administered web-survey instrument. We collected lifestyle information, history of DED diagnosis, types of treatment, frequency of eye-drop usage, symptoms, and the reasons for discontinuing treatment. Statistical analyses including logistic regression were used to evaluate the risk factors of discontinuing ophthalmic follow-up for DED. A past history of clinical DED diagnosis was reported by 155 (15.0%) subjects. Of those, 130 had persistent DED, and 88 (67.7%) of the subjects reported discontinuation of ophthalmic follow-up for DED. The most prevalent reasons for ophthalmic follow-up discontinuation were time restrictions, followed by dissatisfaction with the DED treatment. Duration after DED diagnosis was the only significant risk factor for discontinuing ophthalmic follow-up after adjusting for age and sex (odds ratio = 1.09, 95% confidence interval = 1.02–1.17, p = 0.009). In conclusion, longer DED duration after diagnosis was a significant risk factor for discontinuing ophthalmic follow-up for DED. This study showed that DED ophthalmic follow-up discontinuation involves both medical and non-medical reasons. Clinicians need to be aware of them, and preventative effort is needed to avoid discontinuation. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
Open AccessArticle
Dry Eye Symptoms and Ocular Pain in Veterans with Glaucoma
J. Clin. Med. 2019, 8(7), 1076; https://doi.org/10.3390/jcm8071076 - 22 Jul 2019
Cited by 1
Abstract
Dry eye and glaucoma are two frequently encountered ocular conditions, which can lead to substantial morbidity and decreased quality of life. Patients on topical glaucoma medications are known to be at greater risk for ocular surface symptoms. Veterans seen in the eye clinics [...] Read more.
Dry eye and glaucoma are two frequently encountered ocular conditions, which can lead to substantial morbidity and decreased quality of life. Patients on topical glaucoma medications are known to be at greater risk for ocular surface symptoms. Veterans seen in the eye clinics at the Miami Veterans Affairs Hospital from January to July 2016 completed surveys assessing dry eye and ocular pain symptoms, including the five item Dry Eye Questionnaire (DEQ5). A total of 62 patients with glaucoma completed the survey. Of those, 52 were on glaucoma medications at the time of the survey, with the majority requiring more than one medication to control intraocular pressure. The frequency of mild or greater dry eye symptoms (defined as DEQ5 >6) tended to increase with increasing medication burden, and patients on brimonidine were more likely to report a DEQ5 >6. Patients on three or more glaucoma medications were more likely to report symptoms of shooting pain, dryness, and itchiness. Patients using timolol were more likely to report throbbing and pain by light, while those on latanoprost reported stinging. Our data support an association between increasing number of glaucoma medications and worsening of dry eye symptoms. Patient and medication-associated symptoms can be used to tailor individual medication regimens. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
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Open AccessArticle
Dysfunctional Coping Mechanisms Contribute to Dry Eye Symptoms
J. Clin. Med. 2019, 8(6), 901; https://doi.org/10.3390/jcm8060901 - 24 Jun 2019
Cited by 3
Abstract
Dysfunctional coping behaviors, such as catastrophizing, have been implicated in pain severity and chronicity across several pain disorders. However, the impact of dysfunctional coping has not been examined under the context of dry eye (DE). This study evaluates relationships between catastrophizing and measures [...] Read more.
Dysfunctional coping behaviors, such as catastrophizing, have been implicated in pain severity and chronicity across several pain disorders. However, the impact of dysfunctional coping has not been examined under the context of dry eye (DE). This study evaluates relationships between catastrophizing and measures of DE, including pain severity and pain-related daily interference. The population consisted of patients seen at Miami Veterans Affairs eye clinic between April 2016 and October 2017. Patients filled out standardized questionnaires assessing symptoms of DE and eye pain, non-ocular pain, mental health, coping behaviors (Pain Catastrophizing Scale, PCS), and pain-related daily interference as a perceived impact on quality of life (Multidimensional Pain Inventory, Interference Subscale, MPI-Interference), and all patients underwent an ocular surface examination. In total, 194 patients participated, with a mean age of 58.8 ± 9.6 years, the majority being male, non-Hispanic, and black. PCS (catastrophizing) was correlated with DE symptom severity, including Dry-Eye Questionnaire 5 (DEQ5; r = 0.41, p < 0.0005), Ocular Surface Disease Index (OSDI; r = 0.40, p < 0.0005), and neuropathic-like eye pain (Neuropathic Pain Symptom Inventory-Eye (NPSI-Eye; r = 0.48, p < 0.0005). Most tear metrics, on the other hand, did not correlate with PCS. Linear regressions showed that PCS, non-ocular pain intensity, and number of pain conditions were significant predictors of DEQ5 (overall DE symptoms), while PCS and non-ocular pain intensity were predictors of NPSI-Eye scores, as were insomnia scores and analgesic use. In a separate analysis, PCS and DE symptoms (OSDI) associated with pain-related interference (MPI-Interference) along with non-ocular pain intensity, post-traumatic stress disorder (PTSD), number of pain conditions, and non-Hispanic ethnicity. These findings suggest that catastrophizing is not significantly related to signs of DE, but is strongly associated to pain-related symptoms of DE and daily interference due to pain. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
Open AccessArticle
Characteristics of Individuals with Dry Eye Symptoms without Clinical Diagnosis: Analysis of a Web-Based Survey
J. Clin. Med. 2019, 8(5), 721; https://doi.org/10.3390/jcm8050721 - 21 May 2019
Cited by 2
Abstract
Currently, the available treatment for dry eye disease (DED) varies. The present study aimed to investigate the characteristics of undiagnosed DED and patient-based self-care management for DED based on a web-based survey performed for Tear’s Day in Japan; 1030 participants (301 women) responded; [...] Read more.
Currently, the available treatment for dry eye disease (DED) varies. The present study aimed to investigate the characteristics of undiagnosed DED and patient-based self-care management for DED based on a web-based survey performed for Tear’s Day in Japan; 1030 participants (301 women) responded; 155 participants (72 women) had a clinical diagnosis of DED. We defined undiagnosed DED (n = 116; 54 women) as those with DED symptoms, as evaluated by a frequently used questionnaire despite not having a clinical diagnosis. A multivariate adjusted model indicated that younger age (odds ratio (OR), 0.97 for each one-year decrease; 95% confidence interval (CI), 0.95–0.99), female sex (OR, 2.12; 95% CI, 1.28–3.50), and prolonged visual display terminal usage (OR, 1.12; 95% CI, 1.04–1.21) were risk factors for undiagnosed DED. To investigate the efficacy of self-care management for DED, a sub-analysis was conducted. The number of self-care methods used was significantly higher among women than men. For undiagnosed DED, those with less than three self-care methods had a significantly worse Dry Eye-related Quality-of-Life Score compared with those with diagnosed DED. This study revealed risk factors for undiagnosed DED; individuals with those risk factors need to be clinically assessed and should not rely solely on self-care. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
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Open AccessArticle
Discrepancies in Persistent Dry Eye Signs and Symptoms in Bilateral Pseudophakic Patients
J. Clin. Med. 2019, 8(2), 211; https://doi.org/10.3390/jcm8020211 - 07 Feb 2019
Cited by 2
Abstract
Despite the increased awareness of early prophylaxis and treatment for dry eye disease (DED) during the first few weeks after cataract surgery, the chronic effect of cataract surgery on the risk of ocular surface abnormalities has not been fully explored. This study was [...] Read more.
Despite the increased awareness of early prophylaxis and treatment for dry eye disease (DED) during the first few weeks after cataract surgery, the chronic effect of cataract surgery on the risk of ocular surface abnormalities has not been fully explored. This study was to assess the prevalence of DE subjective symptoms and clinical tests according to the cataract surgery. A total of 172 patients who underwent bilateral cataract surgeries at least 5 months before the recruitment date and 1225 controls with no cataracts were evaluated for their subjective DE symptoms (dry sensation, foreign-body sensation, ocular pain, ocular fatigue, sensitivity to bright light, and blurred vision) and ophthalmic parameters (tear break-up time, keratoconjunctival staining scores, and maximum blinking interval). The presence of subjective DE symptoms was generally inversely associated with cataract surgeries, whereas abnormal clinical tests were more pronounced among postsurgical cataract patients than among controls. Pseudophakic patients showed a 57% increased prevalence of severe keratoconjunctivitis, compared to controls (P = 0.02). In contrast, among subjective DE symptoms, significantly lower odds of sensitivity to bright light were detected among cases than controls; the multivariable-adjusted odds ratio (95% confidence interval) comparing pseudophakic patients with noncataract patients was 0.56 (0.34–0.92) (P = 0.02). In conclusion, persistent tear instability and corneal epitheliopathy were found even at several months or more after cataract surgery. This study demonstrates the importance of evaluating ocular surface conditions in pseudophakic patients, even if they lack DE symptoms. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
Open AccessArticle
Gout as a Risk Factor for Dry Eye Disease: A Population-Based Cohort Study
J. Clin. Med. 2019, 8(1), 62; https://doi.org/10.3390/jcm8010062 - 09 Jan 2019
Cited by 2
Abstract
This study evaluated the effect of gout on the risk of dry eye disease (DED) by using the National Health Insurance Research Database (NHIRD). Data for 30,192 gout patients (21,081 men and 9111 women) and 30,192 non-gout patients (21,005 men and 9187 women) [...] Read more.
This study evaluated the effect of gout on the risk of dry eye disease (DED) by using the National Health Insurance Research Database (NHIRD). Data for 30,192 gout patients (21,081 men and 9111 women) and 30,192 non-gout patients (21,005 men and 9187 women) were analyzed. Approximately 1 million patients were randomly sampled from the NHIRD registry. After applying exclusion criteria, patients diagnosed with gout were enrolled in the study group. Thereafter, each individual in the study group underwent the matching process via the propensity score with another non-gout individual, which constituted the control group. The main outcome was defined as the development of DED in accordance with the corresponding International Classification of Diseases, Ninth Revision. In addition to DED, other risk factors including age, sex, and urbanization, and several co-morbidities were included in the multivariate model. The incidence of DED with the adjusted hazard ratio (aHR) and cumulative probability were evaluated in the gout and non-gout patients. A total of 2913 DED events were observed in the study group, whereas 2631 DED events were observed in the control group. A higher incidence rate ratio was found in the study group after adjustment (aHR: 1.065). Moreover, the cumulative probability indicated a significantly increased risk of DED in the study group (p = 0.001). The other potential risk factors of DED according to the multivariate analysis include older age, female gender, higher degree of urbanization, keratopathy, age-related macular degeneration, glaucoma, cataract, ischemic heart disease, hyperlipidemia, peripheral vascular disease, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, liver disease, and malignancy. In conclusion, gout increased the risk of DED after adjustment, and the risk is positively correlated to a longer disease period. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
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Review

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Open AccessReview
Blood-Based Treatments for Severe Dry Eye Disease: The Need of a Consensus
J. Clin. Med. 2019, 8(9), 1478; https://doi.org/10.3390/jcm8091478 - 17 Sep 2019
Cited by 2
Abstract
The use of blood-based eye drops as therapy for various diseases of the ocular surface has become increasingly popular in ophthalmic practice during recent years. The rationale for their use is based on the promotion of cellular proliferation and migration thanks to the [...] Read more.
The use of blood-based eye drops as therapy for various diseases of the ocular surface has become increasingly popular in ophthalmic practice during recent years. The rationale for their use is based on the promotion of cellular proliferation and migration thanks to the supply of metabolically active substances, in particular growth factors. Blood-derived eye drops have been used for the treatment of several ocular surface disorders, such as dry eye disease, corneal ulcer, persistent epithelial defect, neurotrophic keratitis, ocular surface burn, recurrent corneal erosion, and limbal stem-cell deficiency. Both autologous (from patients themselves) and heterologous (from adult donors or from cord blood sampled at birth)-derived products exist, and each source has specific pros and cons. Despite an extensive literature, several issues are still under debate and the aim of this manuscript is to review the indications, preparation methods and storage, characterization of content, rationale for clinical outcomes, patient stratification, length of treatment, and rationale for repeated treatments at disease relapse. A rationale based on a “5 Ws and 2 Hs” protocol is proposed as a way of thinking, with the attempt to clarify Who, Why, When, Where, What, and How to use these treatment options. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
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Open AccessReview
Dry Eye Disease: Emerging Approaches to Disease Analysis and Therapy
J. Clin. Med. 2019, 8(9), 1439; https://doi.org/10.3390/jcm8091439 - 11 Sep 2019
Cited by 2
Abstract
Dry eye disease (DED) is among the most common ocular disorders affecting tens of millions of individuals worldwide; however, the condition remains incompletely understood and treated. Valuable insights have emerged from multidisciplinary approaches, including immunometabolic analyses, microbiome analyses, and bioengineering. Furthermore, we have [...] Read more.
Dry eye disease (DED) is among the most common ocular disorders affecting tens of millions of individuals worldwide; however, the condition remains incompletely understood and treated. Valuable insights have emerged from multidisciplinary approaches, including immunometabolic analyses, microbiome analyses, and bioengineering. Furthermore, we have seen new developments in clinical assessment approaches and treatment strategies in the recent past. Here, we review the emerging frontiers in the pathobiology and clinical management of DED. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
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Open AccessReview
Dry Eye Disease: A Review of Epidemiology in Taiwan, and its Clinical Treatment and Merits
J. Clin. Med. 2019, 8(8), 1227; https://doi.org/10.3390/jcm8081227 - 15 Aug 2019
Cited by 2
Abstract
Dry eye disease (DED) has become common on a global scale in recent years. There is a wide prevalence of DED in different countries based on various ethnicities and environment. DED is a multifactorial ocular disorder. In addition to advanced age and gender, [...] Read more.
Dry eye disease (DED) has become common on a global scale in recent years. There is a wide prevalence of DED in different countries based on various ethnicities and environment. DED is a multifactorial ocular disorder. In addition to advanced age and gender, such factors as living at high altitude, smoking, pterygium, prolonged use of consumer electronics or overingesting of caffeine or multivitamins are considered to be the major risk factors of DED. We report the DED epidemiology in Taiwan firstly in this article. According to the pathophysiological factors and changes inthe composition of the tear film in DED, it can be categorized into several subtypes, including lipid anomaly dry eye, aqueous tear deficiency, allergic and toxic dry eye among others. Each subtype has its own cause and disease management; therefore, it is important for ophthalmologists to identify the type through literature review and investigation. The management of DED, relies not only on traditional medications such as artificial tears, gels and ointments, but also newer treatment options such as acupuncture, SYL1001, and nanomedicine therapy. We also conducted a comprehensive literature review including common subtypes and treatment of DED. Clearly, more clinical trials are needed to assess the efficacy and safety of the various treatments and common subtypes of DED. Full article
(This article belongs to the Special Issue Dry Eye Syndrome: New Insights on Epidemiology and Management)
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