Purpose To present evidence from the literature and scientific meetings to support fundamental changes in concepts regarding the prevalence, pathogenesis, definition, diagnosis, management of dry eye ...disease (DED) and the prospects for the development of new therapies. Design Analysis and clinical perspective of the literature and recent presentations. Methods Review and interpretation of literature. Results The tear film and ocular surface form an integrated physiologic unit linking the surface epithelia and secretory glands via a neural network. This sensory-driven network regulates secretory activity in quantity and composition, supporting the homeostasis of the system. The tear film forms a metastable covering between blinks, subserving clear vision, and maintains the health and turnover of the ocular surface cells. Disturbance of intrinsic factors such as increasing age; hormonal balance; systemic or local autoimmune disease, or both; systemic drugs or extrinsic factors including topical medications; environmental stress; contact lens wear; or refractive surgery result in a final common pathway of events at the tear film and ocular surface, resulting in DED. Diagnosis of DED and the design of clinical trials for new drugs have been hampered by a lack of correlation between signs and symptoms and flawed endpoints; successful new drug applications likely will require new approaches, such as the use of objective biomarkers for disease severity. Conclusions Recent advances in our knowledge of the causation of DED open opportunities for improving diagnosis and disease management and for developing new, more effective therapies to manage this widely prevalent and debilitating disease state.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A prospective, multisite clinical study (10 sites in the European Union and the United States) evaluated the clinical utility of commonly used tests and tear osmolarity for assessing dry eye disease ...severity.
Three hundred fourteen consecutive subjects between the ages of 18 and 82 years were recruited from the general patient population, 299 of which qualified with complete datasets. Osmolarity testing, Schirmer test without anesthesia, tear film breakup time (TBUT), corneal staining, meibomian dysfunction assessment, and conjunctival staining were performed bilaterally. A symptom questionnaire, the Ocular Surface Disease Index (OSDI), was also administered to each patient. Distributions of clinical signs and symptoms against a continuous composite severity index were evaluated.
Osmolarity was found to have the highest correlation coefficient to disease severity (r(2) = 0.55), followed by conjunctival staining (r(2) = 0.47), corneal staining (r(2) = 0.43), OSDI (r(2) = 0.41), meibomian score (r(2) = 0.37), TBUT (r(2) = 0.30), and Schirmer result (r(2) = 0.17). A comparison of standard threshold-based classification with the composite severity index revealed significant overlap between the disease severities of prospectively defined normal and dry eye groups. Fully 63% of the subjects were found to be poorly classified by combinations of clinical thresholds.
Tear film osmolarity was found to be the single best marker of disease severity across normal, mild/moderate, and severe categories. Other tests were found to be informative in the more severe forms of disease; thus, clinical judgment remains an important element in the clinical assessment of dry eye severity. The results also indicate that the initiation and progression of dry eye is multifactorial and supports the rationale for redefining severity on the basis of a continuum of clinical signs. (ClinicalTrials.gov number, NCT00848198.).
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Purpose: To evaluate the relationship between signs and symptoms of dry eye disease (DED) in a clinic‐based population.
Methods: In a retrospective analysis, clinical signs and symptoms were ...evaluated for 344 subjects (n = 82, normal; n = 263, dry eye), across 11 sites from the EU and United States. Pearson correlations between signs and symptoms (r2) and an independent components analysis (ICA) mixing matrix were derived from the data set. Similar analysis was performed on an independent data set from 200 subjects in a previous study in Munich, Germany.
Results: No correlations above r2 = 0.17 were found between any signs and symptoms, except for corneal and conjunctival staining, which reported an r2 = 0.36. In the multisite study, the average r2 for osmolarity (0.07), tear breakup time (0.12), Schirmer test (0.09), corneal (0.16) and conjunctival staining (0.17), meibomian grading (0.11) and Ocular Surface Disease Index® (0.11) were consistently low. Among patients who showed evidence of DED by consensus of clinical signs, only 57% reported symptoms consistent with a diagnosis of DED. Similar results were observed in the Munich‐based study data set. Each component of the ICA mixing matrix exhibited minimal residual information.
Conclusions: No consistent relationship was found between common signs and symptoms of DED. Each type of measurement provides distinct information about the condition of the ocular surface. These results also demonstrate that symptoms alone are insufficient for the diagnosis and management of DED and argue for a consensus of clinical signs that better reflect all aspects of the disease.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Purpose To evaluate the use of tear osmolarity in the diagnosis of dry eye disease. Design A prospective, observational case series to determine the clinical usefulness of tear osmolarity and ...commonly used objective tests to diagnose dry eye disease. Methods A multicenter, 10-site study consisting of 314 consecutive subjects between 18 and 82 years of age. Bilateral tear osmolarity, tear film break-up time (TBUT), corneal staining, conjunctival staining, Schirmer test, and meibomian gland grading were performed. Diagnostic performance was measured against a composite index of objective measurements that classified subjects as having normal, mild or moderate, or severe dry eye. The main outcome measures were sensitivity, specificity, area under the receiver operating characteristic curve, and intereye variability. Results Of the 6 tests, tear osmolarity was found to have superior diagnostic performance. The most sensitive threshold between normal and mild or moderate subjects was found to be 308 mOsms/L, whereas the most specific was found at 315 mOsms/L. At a cutoff of 312 mOsms/L, tear hyperosmolarity exhibited 73% sensitivity and 92% specificity. By contrast, the other common tests exhibited either poor sensitivity (corneal staining, 54%; conjunctival staining, 60%; meibomian gland grading, 61%) or poor specificity (tear film break-up time, 45%; Schirmer test, 51%). Tear osmolarity also had the highest area under the receiver operating characteristic curve (0.89). Intereye differences in osmolarity were found to correlate with increasing disease severity ( r2 = 0.32). Conclusions Tear osmolarity is the best single metric both to diagnose and classify dry eye disease. Intereye variability is a characteristic of dry eye not seen in normal subjects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Purpose To provide a consensus clinical guideline for management of dry eye disease associated with Sjögren disease by evaluating published treatments and recommending management options. ...Design Consensus panel evaluation of reported treatments for dry eye disease. Methods Using the 2007 Report of the International Workshop on Dry Eye (DEWS) as a starting point, a panel of eye care providers and consultants evaluated peer-reviewed publications and developed recommendations for evaluation and management of dry eye disease associated with Sjögren disease. Publications were graded according to the American Academy of Ophthalmology Preferred Practice Pattern guidelines for level of evidence. Strength of recommendation was according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Results The recommendations of the panel are briefly summarized herein. Evaluation should include symptoms of both discomfort and visual disturbance as well as determination of the relative contribution of aqueous production deficiency and evaporative loss of tear volume. Objective parameters of tear film stability, tear osmolarity, degree of lid margin disease, and ocular surface damage should be used to stage severity of dry eye disease to assist in selecting appropriate treatment options. Patient education with regard to the nature of the problem, aggravating factors, and goals of treatment is critical to successful management. Tear supplementation and stabilization, control of inflammation of the lacrimal glands and ocular surface, and possible stimulation of tear production are treatment options that are used according to the character and severity of dry eye disease. Summary Management guidelines for dry eye associated with Sjögren’s disease are presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Like dry eye disease 15 years ago, blepharitis today is a poorly defined condition about which there is considerable misunderstanding. For a variety of reasons, there is little good data on ...either the prevalence of blepharitis or how eyecare practitioners currently treat it. The work reported herein consists of two recent studies: a telephone survey of a representative sample of the adult US population (n = 5,000) whose purpose was to discover the frequency of common ocular surface symptoms associated with blepharitis; and a study that queried a selected group of ophthalmologists (n = 120) and a similarly selected group of optometrists (n = 84) about the frequency of blepharitis in their practices, the existence comorbid conditions, and their management strategies. This data suggests that blepharitis symptoms are very common in the US population, with younger individuals reporting more, and more frequent, symptoms than older people, contrary to clinical dogma. Ophthalmologists and optometrists report that blepharitis is commonly seen in clinical practice in 37% and 47% of their patients, respectively, and it is widely agreed that meibomian gland dysfunction (MGD) is the most common cause of evaporative dry eye disease In addition, management paradigms are shifting away from more traditional management with antibiotic ointment and warm compress therapy to prescription therapy for anterior and posterior blepharitis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PURPOSE:To evaluate in a general clinic-based cohort of patients with dry eye disease (DED) the distribution of patients with aqueous-deficient or evaporative subtype of DED.
METHODS:Schirmer tests ...and meibomian gland dysfunction (MGD) (Foulks–Bron scoring) were evaluated in both eyes of 299 normal subjects and DED patients (218 women and 81 men) across 10 sites in the European Union and the United States. Using the more severe measurement of the 2 eyes, subjects were considered to have pure aqueous-deficient dry eye (ADDE) with Schirmer values of <7 mm and MGD grades of ≤5. Patients were classified as purely evaporative dry eye with MGD grades of >5 and Schirmer values of ≥7 mm. Subjects were placed into the mixed (hybrid) category if they exhibited both a low Schirmer value of <7 and evidence of MGD with a grade >5.
RESULTS:Of the 224 subjects classified with DED using an objective, composite, disease severity scale, 159 were classified into 1 of 3 categories79 were classified with only MGD, whereas only 23 were classified as purely aqueous deficient, and 57 showed evidence of both MGD and aqueous deficiency. Overall, 86% of these qualified DED patients demonstrated signs of MGD. The remaining 65 patients showed evidence of DED through other clinical signs, without overt evidence of MGD or ADDE, possibly because of the inherent variability of these signs.
CONCLUSIONS:The proportion of subjects exhibiting signs of evaporative dry eye resulting from MGD far outweighs that of subjects with pure ADDE in a general clinic-based patient cohort.
Management of dry eye disease Lemp, Michael A
The American journal of managed care
14, Issue:
3 Suppl
Journal Article
Peer reviewed
The management of dry eye disease (DED) encompasses both pharmacologic and nonpharmacologic approaches, including avoidance of exacerbating factors, eyelid hygiene, tear supplementation, tear ...retention, tear stimulation, and anti-inflammatory agents. Artificial tears are the mainstay of DED therapy but, although they improve symptoms and objective findings, there is no evidence that they can resolve the underlying inflammation in DED. Topical corticosteroids are effective anti-inflammatory agents, but are not recommended for long-term use because of their adverse-effect profiles. Topical cyclosporine--currently the only pharmacologic treatment approved by the US Food and Drug Administration specifically for DED--is safe for long-term use and is disease-modifying rather than merely palliative. Treatment selection is guided primarily by DED severity. Recently published guidelines propose a severity classification based on clinical signs and symptoms, with treatment recommendations according to severity level.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PURPOSETo evaluate the safety and effectiveness of the LipiFlow System compared to the iHeat Warm Compress (WC) for adults with meibomian gland dysfunction (MGD).
METHODSThis was a non-significant ...risk, prospective, open-label, randomized, crossover multicenter clinical trial. One hundred thirty-nine subjects were randomized between LipiFlow (n=69) and WC control (n=70). Subjects in the LipiFlow group received a 12-minute LipiFlow treatment and were reexamined at 1 day, 2 weeks and 4 weeks. Control subjects received a 5-minute iHeat treatment with instructions to perform the same treatment daily for 2 weeks. At 2 weeks, they crossed over (LipiFlow Crossover) and received the LipiFlow treatment. Effectiveness parametersmeibomian gland (MG) assessment, tear break-up time (TBUT) and dry eye symptoms. Safety parametersadverse events, ocular health exam, ocular surface staining, intraocular pressure, visual acuity and discomfort.
RESULTSLipiFlow resulted in significant improvement (P < 0.05) in MG secretion at 2 and 4 weeks (mean ± standard deviation at baseline = 6.3 ± 3.5; 2 weeks = 14.3 ± 8.7; 4 weeks = 16.7 ± 8.7); and TBUT at 2 and 4 weeks(at baseline = 5.5 ± 2.9; 2 weeks = 6.9 ± 5.0; 4 weeks = 7.4 ± 5.5). There was no significant change in MG secretion or TBUT in the control group. LipiFlow resulted in a greater significant reduction in dry eye symptoms than the iHeat WC. The crossover group demonstrated similar significant improvement 2 weeks post-treatment with the LipiFlow. There was no significant difference between groups in the incidence of non-serious, device-related adverse events.
CONCLUSIONThe LipiFlow System was significantly more effective than iHeat WC. These results support its safety and effectiveness in the treatment of MGD and dry eye symptoms.
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