Dry Eye Disease: An Update in 2022 Hakim, Farida E; Farooq, Asim V
JAMA : the journal of the American Medical Association,
2022-Feb-01, Letnik:
327, Številka:
5
Journal Article
Purpose: Dry eye syndrome (DES) is a global issue occurring due to tear deficiency or excessive tear evaporation. It is associated with a variety of symptoms causing ocular discomfort. The purpose of ...the study was to evaluate causative factors, treatment modalities, quality of life, and preservatives used in eye drops. Methods: This prospective, follow-up study was conducted in the ophthalmology outpatient department of a tertiary care teaching hospital. Patients older than 18 years of age of either sex diagnosed with DES and willing to give written informed consent were included. The patients were subjected to the Ocular surface disease index Questionnaire (OSDI Questionnaire) twice; at the time of the first visit and at 15 days follow-up. Results: A male preponderance was observed with a 1.86:1 male-to-female ratio. The mean age of the study population was 29.15 ± 10.07 years. The most common presenting complaints were symptoms related to dryness of the eyes followed by refractive error. Exposure to TV/computer screen for more than 6 hours is the most common causative factor. There was a statistically significant improvement in overall quality of life (QoL) in patients of DES on treatment. However, no significant difference was seen in the improvement of quality of life in comparison with different preservatives used in prescribed eye drops for the treatment of DES. Conclusion: DES can adversely affect the quality of life of patients. Prompt treatment of this condition can significantly improve the patient's QoL. Physicians should be encouraged to perform quality of life evaluations for patients with DES to guide them in treatment with more individual-specific treatment options.
The purpose of this article is to review the evidence for the hypothesis that the core mechanism of dry eye disease (DED) is inflammation, including evidence from recent basic, clinical, and ...translational research involving human patients, animal models, and cell cultures.
Using the key words "dry eye + inflammation," the authors conducted a comprehensive search of the PubMed and Web of Science databases for scientific articles published in English between January 1, 1900 and August 30, 2013 on the role of inflammation in DED in cell cultures, animal models, and humans. The resulting articles were then categorized and reviewed.
The literature search revealed a total of 458 publications, almost all published after 1992. The percentages of original studies and review articles are 77.29% (354) and 22.71% (104), respectively. Among the original studies, the number of reports on human DED is 200 (43.7%), on animal models is 115 (25.1%), and cell cultures is 39 (8.5%). A yearly distributing plot revealed that 76% were published from 2003 to 2011, 53% from 2008 to 2012, and 11% during the first 9 months of 2013. This distribution signifies a rapidly growing awareness of the importance of inflammation in DED pathogenesis.
Inflammation plays a key role in the pathogenesis of DED as evidenced by research using tissue culture, animal models, and subjects with DED. Developing biomarkers for inflammation of the ocular surface will provide improved understanding of the mechanisms leading to DED, classification of the severity of DED, and objective metrics for outcome measures of treatment. The chronicity of the disease suggests that dysregulation of immune mechanisms leads to a cycle of continued inflammation, accompanied by alterations in both innate and adaptive immune responses. Given the underlying mechanism for DED, developing effective and safe anti-inflammatory treatments is likely to be beneficial for patients with DED.
We examined symptoms, tear stability, visual function, and conjunctival cytology in eyes with an unstable tear film (UTF), expressed as a short tear film breakup time without epithelial damage or low ...tear secretion, and compared the results with those from eyes with aqueous deficiency (AD) associated with epithelial damage, and healthy eyes.
We divided the patients with ocular discomfort into 2 groups according to the breakup time, Schirmer value, and epithelial staining score: UTF group (≤5 seconds, >5 mm, and <3 points; 21 eyes of 21 patients) and AD group (≤5 seconds, ≤5 mm, and ≥3 points; 21 eyes of 21 patients). We examined all patients and 17 healthy subjects for symptoms, tear functions, tear film stability by tear film lipid layer interferometry and tear film analysis system, and functional visual acuity. Conjunctival impression cytology was performed to investigate changes in goblet cell density, squamous metaplasia, and messenger RNA expression of MUC5AC and MUC16.
The symptom scores, tear film analysis system index, and functional visual acuity testing were significantly worse in the UTF and AD groups compared with those in the control group (P < 0.05). The messenger RNA expression levels of MUC5AC and MUC16 were significantly lower in UTF and AD eyes compared with those in the control eyes (P < 0.0001).
An UTF itself can cause dry eye symptoms and visual disturbance comparable with those of AD dry eyes.
Neuroinflammation plays an important role in the pathogenesis of ocular surface disease, including dry eye disease (DED), but little is known about the contribution of substance P (SP) to DED. In ...this study, we investigated the expression of SP at the ocular surface and evaluated its effect on maturation of antigen-presenting cells (APCs), the key cell component involved in the induction of type 17 helper T-cell (Th17) response in DED. The effect of topical blockade of SP signaling was further investigated using neurokinin-1 receptor (NK1R) inhibitors on APC maturation, Th17 cell activation, and disease severity in a mouse model of DED. The results demonstrate that SP is constitutively expressed at the ocular surface, and trigeminal ganglion neurons are the major source of SP in DED. SP derived from trigeminal ganglion enhanced the expression of major histocompatibility complex class II maturation marker by bone marrow–derived dendritic cells, an effect that is abrogated by blockade of SP signaling using NK1R antagonist spantide. Finally, using a well-established murine model of DED, topical treatment of DED mice with NK1R antagonists CP-99,994 and L-733,060 suppressed APC acquisition of major histocompatibility complex class II, reduced Th17 cell activity, and ameliorated DED severity. These findings are of translational value, as they suggest that antagonizing NK1R-mediated SP signaling may be an effective strategy in suppressing Th17-mediated ocular surface disease.
In 2014, the overall rate of smartphone use in Korea was 83 and 89.8 % in children and adolescents. The rate of smartphone use differs according to region (urban vs. rural) and age (younger grade vs. ...older grade). We investigated risk and protective factors associated with pediatric dry eye disease (DED) in relation to smartphone use rate according to region and age.
We enrolled 916 children and performed an ocular exam that included slit lamp exam and tear break-up time. A questionnaire administered to children and their families consisted of video display terminal (VDT) use, outdoor activity, learning, and modified ocular surface disease index (OSDI) score. DED was defined based on the International Dry Eye Workshop guidelines (Objective signs: punctate epithelial erosion or short tear break-up time; subjective symptoms: modified OSDI score) We performed statistical analysis of risk factors and protective factors in children divided into groups as follows: DED vs. control, urban vs. rural, younger grade (1st to 3rd) vs. older grade (4th to 6th).
A total of 6.6 % of children were included in the DED group, and 8.3 % of children in the urban group were diagnosed with DED compared to 2.8 % in the rural group (P = 0.03). The rate of smartphone use was 61.3 % in the urban group and 51.0 % in the rural group (P = 0.04). In total, 9.1 % of children in the older-grade group were diagnosed with DED compared to 4 % in the younger-grade group (P = 0.03). The rate of smartphone use was 65.1 % in older-grade children and 50.9 % in younger-grade children (P < 0.001). The mean daily duration of smartphone use was longer in the DED group than controls (logistic regression analysis, P < 0.001, OR = 13.07), and the mean daily duration of outdoor activities was shorter in the DED group than controls (logistic regression analysis, P < 0.01, OR = 0.33). After cessation of smartphone use for 4 weeks in the DED group, both subjective symptoms and objective signs had improved.
Smartphone use in children was strongly associated with pediatric DED; however, outdoor activity appeared to be protective against pediatric DED. Older-grade students in urban environments had DED risk factors (long duration of smartphone use), and a short duration of outdoor activity time. Therefore, close observation and caution are needed when older children in urban areas use smartphones.
Primary Sjögren’s syndrome and the eye Bjordal, Oddbjørn; Norheim, Katrine Brække; Rødahl, Eyvind ...
Survey of ophthalmology,
March-April 2020, 2020 Mar - Apr, 2020-03-00, 20200301, Letnik:
65, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Primary Sjögren syndrome is an autoimmune disease that mainly affects exocrine glands such as the salivary and lacrimal glands. In addition, systemic involvement is common. Primary Sjögren syndrome ...is of particular interest to ophthalmologists as it constitutes an important differential diagnosis in conditions with dry eye disease. In addition, ocular tests for more precisely diagnosing and monitoring primary Sjögren syndrome have become increasingly important, and new therapeutics for local and systemic treatment evolve as a result of increased understanding of immunological mechanisms and molecular pathways in the pathogenesis of primary Sjögren syndrome. We provide an update of interest to ophthalmologists regarding pathogenesis, diagnosis, investigative procedures, and treatment options.
The aim of this study is to demonstrate the prevalence of self-reported mask-associated dry eye (MADE) in health-care professionals and the possible risk factors that give rise to MADE.
A ...self-administered questionnaire consisting of 12 questions about MADE and possible risk factors that give rise to MADE was created on web-based "google forms" application, and was then sent to 437 healthcare professionals working in a coronavirus-19 (COVID-19) pandemic hospital, using common telecommunication devices.
Three hundred and thirty-three of the 437 health-care professionals, who answered the questionnaire, were included in the study. The prevalence of self-reported MADE among these health-care professionals was found to be 70% (n = 233). Having at least one of the symptoms of dry eye while not having a mask on and advanced age were determined as the possible risk factors for MADE (p = .02 and p < .001, respectively). The clinical examinations of the 195 participants, who had self-reported MADE and accepted the invitation to undergo a clinical evaluation with respect to the symptoms of MADE, revealed that only 60 (30.7%) of these participants had aqueous-type dryness with staining on the ocular surface with fluorescein.
The high prevalence of self-reported MADE among health-care professionals can be attributed to the prolonged use of masks associated with longer working hours. Therefore, it is important that the ocular complaints of professionals are addressed by ophthalmology consultants/ophthalmologists during these difficult times.
Background
Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti‐inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA eyedrops have been ...approved by US Food and Drug Administration for managing dry eye: Restasis (CsA 0.05%, Allergan Inc, Irvine, CA, USA), approved in 2002, and Cequa (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA), approved in 2018. Numerous clinical trials have been performed to assess the effectiveness and safety of CsA for dry eye; however, there is no universal consensus with regard to its effect.
Objectives
To assess the effectiveness and safety of topical CsA in the treatment of dry eye.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 16 February 2018.
Selection criteria
We included randomized controlled trials (RCTs) of people with dry eye regardless of age, sex, severity, etiology, or classification of dry eye. We included RCTs in which different concentrations of topical CsA were compared with one another or with artificial tears, placebo, or vehicle. We also included RCTs in which CsA in combination with artificial tears was compared to artificial tears alone.
Data collection and analysis
We followed the standard Cochrane methodology and assessed the certainty of the evidence using GRADE.
Main results
We included 30 RCTs (4009 participants) with follow‐up periods ranging from 6 weeks to 12 months. We studied dry eye of various severity and underlying causes. The interventions investigated also varied across RCTs: CsA versus artificial tears; CsA with artificial tears versus artificial tears alone; and in some studies, more than one concentration of CsA. Artificial tears were used as adjunctive to study medication in all but five trials. Almost all trials had deficiencies in the reporting of results (e.g. reporting P values or direction only), precluding the calculation of between‐group estimates of effect or meta‐analysis.
Eighteen trials compared topical CsA 0.05% plus artificial tears versus vehicle plus artificial tears or artificial tears alone. One trial reported subjective symptoms of dry eye at 6 months and the results were in favor of CsA (mean difference (MD) ‐4.80, 95% confidence interval (CI) ‐6.41 to ‐3.19; low‐certainty evidence). Two trials reported MD in ocular surface dye staining at 6 months, but the results were inconsistent in these two trials (MD −0.35, 95% CI −0.69 to −0.01 in one and MD 0.58, 95% CI 0.06 to 1.10 in the other; low‐certainty evidence). Four trials reported MD in Schirmer test scores at 6 months and the estimates ranged from ‐4.05 (95% CI ‐6.67 to ‐1.73) to 3.26 (95% CI ‐1.52 to 5.00) (low‐certainty evidence). Three trials reported risk ratio (RR) of improved Schirmer test scores at 6 months; estimates ranged from 0.98 (95% CI 0.83 to 1.17) to 3.50 (95% CI 2.09 to 5.85) (low‐certainty evidence). Four trials reported MD in tear film stability measured by tear break‐up time at 6 months and the estimates ranged from ‐1.98 (95% CI ‐3.59 to ‐0.37) to 1.90 (95% CI 1.44 to 2.36) (low‐certainty evidence). Three trials reported RR of improved tear break‐up time at 6 months and the estimates ranged from 0.90 (95% CI 0.77 to 1.04) to 4.00 (95% CI 2.25 to 7.12) (low‐certainty evidence). Three trials reported frequency of artificial tear usage at 6 months without providing any estimates of effect; the direction of effect seem to be in favor of CsA (low‐certainty evidence). Because of incomplete reporting of the results data or considerable statistical heterogeneity, we were only able to perform a meta‐analysis on mean conjunctival goblet cell density. Mean conjunctival goblet cell density in the CsA treated group may be greater than that in the control group at the end of follow‐up at four and 12 months (MD 22.5 cells per unit, 95% CI 16.3 to 28.8; low‐certainty evidence). All but two trials reported adverse events that included burning and stinging. Participants treated with CsA may be more likely to have treatment‐related adverse events than those who treated with vehicle (RR 1.33, 95% CI 1.00 to 1.78; low‐certainty evidence).
Other comparisons evaluated were CsA 0.05% plus artificial tears versus higher concentrations of CsA plus artificial tears (4 trials); CsA 0.05% versus placebo or vehicle (4 trials); CsA 0.1% plus artificial tears versus placebo or vehicle plus artificial tears (2 trials);
CsA 0.1% cationic emulsion plus artificial tears versus vehicle plus artificial tears (2 trials); CsA 1% plus artificial tears versus placebo plus artificial tears (3 trials); and CsA 2% plus artificial tears versus placebo plus artificial tears (3 trials). Almost all of these trials reported P value or direction of effect only (mostly in favor of CsA), precluding calculation of between‐group effect estimates or meta‐analyses.
Authors' conclusions
Despite the widespread use of topical CsA to treat dry eye, we found that evidence on the effect of CsA on ocular discomfort and ocular surface and tear film parameters such as corneal fluorescein staining, Schirmer's test, and TBUT is inconsistent and sometimes may not be different from vehicle or artificial tears for the time periods reported in the trials. There may be an increase in non‐serious, treatment‐related adverse effects (particularly burning) in the CsA group. Topical CsA may increase the number of conjunctival goblet cells. However, current evidence does not support that improvements in conjunctival mucus production (through increased conjunctival goblet cells) translate to improved symptoms or ocular surface and tear film parameters. All published trials were short term and did not assess whether CsA has longer‐term disease‐modifying effects. Well‐planned, long‐term, large clinical trials are needed to better assess CsA on long‐term dry eye‐modifying effects. A core outcome set, which ideally includes both biomarkers and patient‐reported outcomes in the field of dry eye, is needed.
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