Cutting-Edge Topics in Dry Eye Disease

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

Deadline for manuscript submissions: closed (1 December 2020) | Viewed by 32640

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Special Issue Editor

Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea
Interests: corneal and external eye disease; cataract and refractive surgery; tear film and dry eye disease; ocular pharmacology and therapeutics; aging and anti-oxidants

Special Issue Information

Dear Colleagues,

Diagnosis and treatment of dry eye disease is certainly one of the fastest evolving fields of modern ophthalmology. In recent years, multiple novel diagnosis and treatment approaches regarding dry eye disese and Meibomian gland dysfunction as well as related medical therapy have been introduced. It is not surprising that these approaches help to address clinical problems better than before, but also led to many additional questions that need to be addressed, such as biomarkers, neuropathic corneal pain, efficacy of anti-oxidative agents, and so on.

It is the aim of this Special Issue to provide an update regarding current and upcoming diagnostic and therapeutic options in the field of dry eye. Therefore, we would like to invite original research, state-of-the-art reviews, and viewpoints. In particular, we would like to encourage the submission of manuscripts covering important items regarding therapeutic agents or devices needed for an optimal long-term outcome of dry eye.

We look forward to your submissions!

Prof. Dr. Kyung Chul Yoon
Guest Editor

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Keywords

  • Tear film
  • Lacrimal gland
  • Ocular surface inflammation
  • Dry eye disease
  • Meibomian gland dysfunction
  • Neurosensoary abnormality
  • Biomarker
  • Therapeutic agent or device

Published Papers (11 papers)

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16 pages, 545 KiB  
Article
Relation of Dietary Fatty Acids and Vitamin D to the Prevalence of Meibomian Gland Dysfunction in Japanese Adults: The Hirado–Takushima Study
J. Clin. Med. 2021, 10(2), 350; https://doi.org/10.3390/jcm10020350 - 18 Jan 2021
Cited by 8 | Viewed by 2635
Abstract
Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated [...] Read more.
Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated the relation of MGD prevalence to dietary intake of fatty acids (FAs) and vitamin D among a Japanese population. Subjects comprised 300 adults aged 20 to 92 years residing on Takushima Island. MGD was diagnosed on the basis of subjective symptoms, lid margin abnormalities, and meibomian gland obstruction. Dietary FA and vitamin D intake was estimated with a brief-type self-administered diet history questionnaire. MGD prevalence was 35.3%. Multivariate adjusted odds ratios (95% confidence intervals) between extreme quintiles of intake for MGD prevalence were 0.40 (0.16–0.97) for total fat, 0.40 (0.17–0.97) for saturated FAs, 0.40 (0.17–0.97) for oleic acid, 0.52 (0.23–1.18) for n-3 PUFAs, 0.63 (0.27–1.49) for n-6 PUFAs, 1.32 (0.59–2.95) for the n-6/n-3 PUFA ratio, and 0.38 (0.17–0.87) for vitamin D. Total fat, saturated FA, oleic acid, and vitamin D intake may thus be negatively associated with MGD prevalence in the Japanese. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)
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10 pages, 620 KiB  
Article
Proposed Algorithm for Management of Meibomian Gland Dysfunction Based on Noninvasive Meibography
J. Clin. Med. 2021, 10(1), 65; https://doi.org/10.3390/jcm10010065 - 27 Dec 2020
Cited by 12 | Viewed by 3162
Abstract
Although the pathophysiology of meibomian gland dysfunction (MGD) remains incompletely understood, many treatment options have recently become available. According to an international workshop report, treatment selection for MGD should be based on a comprehensive stage classification dependent on ocular symptoms, lid margin abnormalities, [...] Read more.
Although the pathophysiology of meibomian gland dysfunction (MGD) remains incompletely understood, many treatment options have recently become available. According to an international workshop report, treatment selection for MGD should be based on a comprehensive stage classification dependent on ocular symptoms, lid margin abnormalities, meibum grade, and ocular surface staining. However, it is often difficult to evaluate all parameters required for such classification in routine clinical practice. We have now retrospectively evaluated therapeutic efficacy in MGD patients who received five types of treatment in the clinic setting: (1) meibocare (application of a warm compress and practice of lid hygiene), (2) meibum expression plus meibocare, (3) azithromycin eyedrops plus meibocare, (4) thermal pulsation therapy plus meibocare, or (5) intense pulsed light (IPL) therapy plus meibocare. Patients in each treatment group were classified into three subsets according to the meiboscore determined by noncontact meibography at baseline. Eyes in the IPL group showed improvement even if the meiboscore was high (5 or 6), whereas meibocare tended to be effective only if the meiboscore was low (1 or 2). The meiboscore may thus serve to guide selection of the most appropriate treatment in MGD patients. Prospective studies are warranted to confirm these outcomes. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)
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14 pages, 1124 KiB  
Article
Efficacy and Safety of Houttuynia Eye Drops Atomization Treatment for Meibomian Gland Dysfunction-Related Dry Eye Disease: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial
J. Clin. Med. 2020, 9(12), 4022; https://doi.org/10.3390/jcm9124022 - 12 Dec 2020
Cited by 8 | Viewed by 2458
Abstract
Purpose: To evaluate the efficacy and safety of Houttuynia eye drops (a Chinese traditional medicine) atomization treatment in meibomian gland dysfunction (MGD)-related dry eye disease (DED) patients. Methods: A total of 240 eligible patients diagnosed with MGD-related DED were assigned either Houttuynia eye [...] Read more.
Purpose: To evaluate the efficacy and safety of Houttuynia eye drops (a Chinese traditional medicine) atomization treatment in meibomian gland dysfunction (MGD)-related dry eye disease (DED) patients. Methods: A total of 240 eligible patients diagnosed with MGD-related DED were assigned either Houttuynia eye drops or placebo for atomization once daily for four weeks in a multi-center, randomized, double-blind, placebo-controlled clinical study. Primary outcome evaluations used included eye symptom score (using the Chinese Dry Eye Questionnaire), meibum quality, and tear break-up time (TBUT), while safety evaluations included adverse events (AEs), visual acuity, and intraocular pressure monitoring. Indicators were measured at baseline as well as one week, two weeks, and four weeks after treatment. Results: Primary outcome measures of the Houttuynia group were improved compared with their placebo counterparts following four-week treatment. Eye symptom scores were significantly reduced relative to the baseline in the Houttuynia group (mean ± standard error of the mean, 9.00 ± 0.61) compared with the placebo group (6.29 ± 0.55; p = 0.0018). Reduction in meibum quality score in the Houttuynia group (0.91 ± 0.10) was also significantly higher compared with the placebo group (0.57 ± 0.10; p = 0.0091), while TBUT in the treatment group (6.30 ± 0.22) was also longer than in the latter (5.60 ± 0.24; p = 0.0192). No medication-related adverse events were observed. Conclusions: Atomization treatment with Houttuynia eye drops is both clinically and statistically effective for the treatment of mild to moderate MGD-related DED patients. This approach is generally safe and was tolerated well by patients. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)
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13 pages, 11615 KiB  
Article
High Molecular Weight Hyaluronan Promotes Corneal Nerve Growth in Severe Dry Eyes
J. Clin. Med. 2020, 9(12), 3799; https://doi.org/10.3390/jcm9123799 - 24 Nov 2020
Cited by 6 | Viewed by 3655
Abstract
The purpose of this study was to investigate the effect of high molecular weight hyaluronan (HMWHA) eye drops on subbasal corneal nerves in patients suffering from severe dry eye disease (DED) and to evaluate the damage of subbasal corneal nerves associated with severe [...] Read more.
The purpose of this study was to investigate the effect of high molecular weight hyaluronan (HMWHA) eye drops on subbasal corneal nerves in patients suffering from severe dry eye disease (DED) and to evaluate the damage of subbasal corneal nerves associated with severe DED. Designed as an international, multicenter study, 16 patients with symptoms of at least an Ocular Surface Disease Index (OSDI) score of 33, and corneal fluorescein staining (CFS) of at least Oxford grade 3, were included and randomized into two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the baseline visit, and after eight weeks, the subbasal nerve plexus of 16 patients were assessed by confocal laser scanning microscopy (CSLM). The images were submitted to a masked reading center for evaluation. Results showed a significant increase of total nerve fiber lengths (CNFL) in the HMWHA group (p = 0.030) when compared to the control group, where the total subbasal CNFL did not significantly change from baseline to week 8. We concluded that in severe DED patients, HMWHA from topically applied eye drops could cross the epithelial barrier and reach the subbasal nerve plexus, where it exercised a trophic effect. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)
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9 pages, 334 KiB  
Article
Treatment Response to Gabapentin in Neuropathic Ocular Pain Associated with Dry Eye
J. Clin. Med. 2020, 9(11), 3765; https://doi.org/10.3390/jcm9113765 - 22 Nov 2020
Cited by 11 | Viewed by 3010
Abstract
Purpose: To investigate the response to gabapentin treatment in patients with dry eye (DE) accompanied by features of neuropathic ocular pain (NOP), and to analyze the differences between clinical manifestations of the groups according to treatment response. Methods: We retrospectively reviewed the records [...] Read more.
Purpose: To investigate the response to gabapentin treatment in patients with dry eye (DE) accompanied by features of neuropathic ocular pain (NOP), and to analyze the differences between clinical manifestations of the groups according to treatment response. Methods: We retrospectively reviewed the records of 35 patients with DE accompanied by NOP features and obtained information on their medical history and previous ocular history. The patients underwent clinical examinations of the tear film, ocular surface, and meibomian gland and completed the Ocular Pain Assessment Survey (OPAS). One month after treatment with topical eye drops, add-on of gabapentin treatment was determined according to the Wong–Baker FACES Pain Rating Scale (WBFPS). A reduction of 2 points or more on the WBFPS was considered a positive treatment response. Enrolled patients were divided into three groups according to the treatment response: topical treatment response group (group 1, n = 11); gabapentin response group (group 2, n = 13); and gabapentin non-response group (group 3, n = 11). The medical history, clinical parameters, and OPAS scores were compared between groups. Results: The incidence of systemic comorbidities was higher in group 2 than in other groups. The corneal staining scores were lower in groups 2 and 3 than in group 1. Among the treatment response groups, group 2 showed improvements in OPAS scores of ocular pain severity, pain other than eyes, and quality of life, while group 1 showed improved OPAS scores of ocular pain severity and ocular associated factors. Group 2 exhibited lower scores of pains aggravated by mechanical and chemical stimuli than group 3. Conclusions: Gabapentin could be effective in patients who have systemic comorbidity and less pain evoked by mechanical and chemical stimuli for the treatment of DE patients with NOP, which is refractory to topical treatment. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)
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25 pages, 2279 KiB  
Article
The HYLAN M Study: Efficacy of 0.15% High Molecular Weight Hyaluronan Fluid in the Treatment of Severe Dry Eye Disease in a Multicenter Randomized Trial
J. Clin. Med. 2020, 9(11), 3536; https://doi.org/10.3390/jcm9113536 - 02 Nov 2020
Cited by 11 | Viewed by 4057
Abstract
The aim of the HYLAN M study was to investigate if symptoms and/or signs of patients suffering from severe dry eye disease (DED) can be improved by substituting individually optimized artificial tear therapy by high molecular weight hyaluronan (HMWHA) eye drops. In this [...] Read more.
The aim of the HYLAN M study was to investigate if symptoms and/or signs of patients suffering from severe dry eye disease (DED) can be improved by substituting individually optimized artificial tear therapy by high molecular weight hyaluronan (HMWHA) eye drops. In this international, multicenter study, patients with symptoms of at least ocular surface disease index (OSDI) 33 and corneal fluorescein staining (CFS) of at least Oxford grade 3 were included. A total of 84 per-protocol patients were randomized in two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the week 8 visit, the average OSDI of the verum group had improved by 13.5 as compared to the control group (p = 0.001). The best corrected visual acuity (BCVA) had improved by 0.04 logMAR (p = 0.033). CFS, tear film break-up time (TBUT), Schirmer I, lid wiper epitheliopathy (LWE), mucocutaneous junction (Yamaguchi score), and tear osmolarity were not significantly different between the verum and control groups (p > 0.050). We conclude that for most patients with severe DED, 0.15% HMWHA eye drops provide excellent improvement of symptoms without impairment of dry eye signs. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)
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13 pages, 723 KiB  
Article
Multicenter Study of Intense Pulsed Light for Patients with Refractory Aqueous-Deficient Dry Eye Accompanied by Mild Meibomian Gland Dysfunction
J. Clin. Med. 2020, 9(11), 3467; https://doi.org/10.3390/jcm9113467 - 28 Oct 2020
Cited by 12 | Viewed by 2659
Abstract
Aqueous-deficient dry eye (ADDE) and meibomian gland dysfunction (MGD) can be refractory to therapy. Intense pulsed light (IPL) was recently introduced as an effective treatment for MGD. We here evaluated the efficacy of IPL combined with MG expression (MGX) compared with MGX alone [...] Read more.
Aqueous-deficient dry eye (ADDE) and meibomian gland dysfunction (MGD) can be refractory to therapy. Intense pulsed light (IPL) was recently introduced as an effective treatment for MGD. We here evaluated the efficacy of IPL combined with MG expression (MGX) compared with MGX alone (n = 23 and 20, respectively) for patients with refractory ADDE with mild MGD at three sites. Symptom score, visual acuity (VA), noninvasive breakup time (NIBUT) and lipid layer thickness (LLT) of the tear film, lid margin abnormalities, fluorescein BUT (FBUT), fluorescein staining, tear meniscus height (TMH), meibum grade, meiboscore, and Schirmer’s test value were assessed at baseline and 1 and 3 months after treatment. LLT, plugging, vascularity, FBUT and NIBUT were improved only in the IPL-MGX group at three months compared with baseline. All parameters with the exception of VA, meiboscore, TMH, Schirmer’s test value were also improved in the IPL-MGX group compared with the control group at three months, as was VA in patients with central corneal epitheliopathy. Although IPL-MGX does not affect aqueous layer, the induced improvement in quality and quantity of the lipid layer may increase tear film stability and ameliorate symptoms not only for evaporative dry eye but for ADDE. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)
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8 pages, 867 KiB  
Article
Evaluation of Strip Meniscometry and Association with Clinical and Demographic Variables in a Community Eye Study (in Bangladesh)
J. Clin. Med. 2020, 9(10), 3366; https://doi.org/10.3390/jcm9103366 - 20 Oct 2020
Cited by 5 | Viewed by 2363
Abstract
Strip meniscometry (SM) is a relatively new technique for evaluating inferior tear meniscus. We described SM in an epidemiology study and its potential associations with clinical and tear parameters. This cross-sectional study involved 1050 factory garment workers in Gazipur, Bangladesh. The Ocular Surface [...] Read more.
Strip meniscometry (SM) is a relatively new technique for evaluating inferior tear meniscus. We described SM in an epidemiology study and its potential associations with clinical and tear parameters. This cross-sectional study involved 1050 factory garment workers in Gazipur, Bangladesh. The Ocular Surface Disease Index (OSDI) questionnaire and a standard examination for dry eye and meibomian gland dysfunction (MGD), including the five-second SM, were performed by a single ophthalmologist. The participants’ ages were 35.56 ± 12.12 years (range 18–59), with 53.8% women. The overall SM was 7.7 ± 3.6 mm, with skewness of 0.126 and kurtosis of 1.84 in frequency distribution. SM values were significantly lower in men than women, and significantly correlated with schirmers (r = 0.71) and tear break up time (TBUT) (r = 0.89). A lower SM value was associated with higher OSDI, lower Schirmer test, increased MG severity and lower TBUT. In multivariable analysis, when adjusted by age, SM values remained associated with schirmers and TBUT, and inversely associated with OSDI. In a separate regression model, higher SM was associated with increasing age, reduced severity of MGD grading, and increased TBUT. To conclude, SM is a rapid clinical test associated with dry eye symptoms and signs, with findings affected by both tear secretion and tear stability. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)
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12 pages, 1269 KiB  
Article
Investigation of Meibomian Gland Function and Dry Eye Disease in Patients with Graves’ Ophthalmopathy
J. Clin. Med. 2020, 9(9), 2814; https://doi.org/10.3390/jcm9092814 - 31 Aug 2020
Cited by 15 | Viewed by 2746
Abstract
We prospectively evaluated the relationship between meibomian gland dysfunction (MGD) and Graves’ ophthalmopathy (GO) in 19 patients (38 eyes) with subjective dry eye symptoms, compared to 14 age-matched normal participants (14 eyes). Extraocular muscle and lacrimal gland enlargement were evaluated by magnetic resonance [...] Read more.
We prospectively evaluated the relationship between meibomian gland dysfunction (MGD) and Graves’ ophthalmopathy (GO) in 19 patients (38 eyes) with subjective dry eye symptoms, compared to 14 age-matched normal participants (14 eyes). Extraocular muscle and lacrimal gland enlargement were evaluated by magnetic resonance imaging (MRI). Ocular surface examinations included fluorescein staining for keratoconjunctival epithelial damage, tear breakup time (TBUT) evaluation, and Schirmer’s test. Dry eye symptoms were evaluated with the Dry Eye-related Quality-of-Life Score (DEQS) questionnaire. Lid-margin abnormalities, meibum grade, and meiboscores were assessed using meibography. Clinical activity scores and T2 signal intensity ratios were used to define GO activity. All GO patients had obstructive MGD and 79% exhibited levator muscle enlargement. Ocular surface parameters of TBUT (p = 0.000), meibum score (p = 0.000), eyelid vasculitis (p = 0.000), meiboscore of the upper lid (p = 0.002), total meiboscores (p = 0.001), and DEQS (p = 0.000) significantly differed between GO patients and normal subjects. In addition, GO patients had significantly more abnormalities of the central region of the upper eyelid than normal subjects (p = 0.000). Thus, MGD might be related to eye discomfort and deterioration of the ocular surface in GO patients. Inflammation and morphological meibomian gland changes might be characteristic of GO. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)
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12 pages, 246 KiB  
Article
Association of Systemic Comorbidities with Dry Eye Disease
J. Clin. Med. 2020, 9(7), 2040; https://doi.org/10.3390/jcm9072040 - 29 Jun 2020
Cited by 12 | Viewed by 2190
Abstract
We investigated the association between dry eye disease and systemic comorbidities, including dry eye subtype, quality of life (QOL) and health utility among patients with dry eye disease. This cross-sectional, observational study enrolled 449 patients with dry eye disease (386 females; mean age, [...] Read more.
We investigated the association between dry eye disease and systemic comorbidities, including dry eye subtype, quality of life (QOL) and health utility among patients with dry eye disease. This cross-sectional, observational study enrolled 449 patients with dry eye disease (386 females; mean age, 62.6 ± 15.7 [range, 21–90] years). Ophthalmic examination findings included tear film break-up time (TBUT), Schirmer I value and keratoconjunctival staining score. QOL and health utility were evaluated using the Dry Eye-Related Quality-of-Life Score (DEQS) and Human Utility Index Mark 3 (HUI-3), respectively. Background information, including systemic comorbidities, was obtained. Prevalence of systemic comorbidities was 48.8% (219/449). No significant difference occurred between DEQS and systemic comorbidity. However, patients with dry eye disease and systemic comorbidities (depression and insomnia) exhibited significantly worse ocular surface parameters, particularly regarding TBUT, than those without. Dry eye disease with insomnia or depression comorbidity significantly correlated with friction-related diseases (including conjunctivochalasis or lid wiper epitheliopathy). A high prevalence of several systemic comorbidities occurred in patients with dry eye disease. This study shows an association between ocular signs and systemic comorbidities, particularly depression and insomnia. Ophthalmologists should be aware of patients’ systemic comorbidities in the diagnosis and management of dry eye disease. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)

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7 pages, 656 KiB  
Brief Report
Topical TRPM8 Agonist for Relieving Neuropathic Ocular Pain in Patients with Dry Eye: A Pilot Study
J. Clin. Med. 2021, 10(2), 250; https://doi.org/10.3390/jcm10020250 - 12 Jan 2021
Cited by 20 | Viewed by 2431
Abstract
Background: Activation of TRPM8, a cold-sensing receptor located on the cornea and eyelid, has the potential to relieve the neuropathic ocular pain (NOP) in dry eye (DE) by inhibiting other aberrant nociceptive inputs. We aimed to investigate the effect of a topical TRPM8 [...] Read more.
Background: Activation of TRPM8, a cold-sensing receptor located on the cornea and eyelid, has the potential to relieve the neuropathic ocular pain (NOP) in dry eye (DE) by inhibiting other aberrant nociceptive inputs. We aimed to investigate the effect of a topical TRPM8 agonist, cryosim-3 (C3), on relieving DE-associated NOP. Methods: We conducted a prospective pilot study of 15 patients with DE-associated NOP. These patients applied topical C3 to their eyelid, 4 times/day for 1 month. The patients underwent clinical examinations. They also completed the Ocular Pain Assessment Survey (OPAS), which is a validated questionnaire for NOP, at baseline, 1 week, and 1 month after treatment. Result: At 1 week, the OPAS scores of eye pain intensity, quality of life (driving/watching TV, general activity, sleep, and enjoying life/relations with other people), and associated factors (burning sensation, light sensitivity, and tearing) improved. The total OPAS scores of eye pain intensity, quality of life, and associated factors remained improved at 1 month. The Schirmer test scores also improved at 1 month. Conclusion: TRPM8 agonist (C3) could be a novel agent for treating patients with DE-associated NOP who are unresponsive to conventional treatments. Full article
(This article belongs to the Special Issue Cutting-Edge Topics in Dry Eye Disease)
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