Quantitative Assessment of Lid Margin Vascularity Using Swept-Source Optical Coherence Tomography Angiography.

Purpose: To evaluate the ability of swept-source optical coherence tomography angiography (SS-OCTA) to assess lid margin vascularity. Methods: This prospective, cross-sectional trial enrolled 125 participants, including 15 control subjects and 110 meibomian gland dysfunction (MGD) patients. Lid margin blood flow density (LMBFD) was obtained using SS-OCTA. LMBFD was assessed for repeatability in 54 of 125 participants and for reproducibility in 23 of 125 participants. The efficacy of LMBFD was validated in the 125 participants, who were divided into mild (n = 46), moderate (n = 42), and severe groups (n = 37) according to the lid margin vascularity severity shown in the slit-lamp photographs. Correlations between LMBFD and MG-related parameters, such as ocular surface disease index (OSDI), fluorescein tear break-up time (FTBUT), cornea fluorescein staining (CFS), lid margin score (LMS), and meibomian gland expressibility (ME), were analyzed in all 125 participants. Results: Repeatability and reproducibility coefficients were satisfactorily high in the scan mode with a scan area of 6 mm × 6 mm (intraclass correlation coefficient [ICC] repeatability = 0.905; ICC reproducibility = 0.986) and a scan area of 9 mm × 9 mm (ICC repeatability = 0.888; ICC reproducibility = 0.988). The LMBFD gradually increased in the mild, moderate, and severe groups (P < 0.001). LMBFD was significant correlated with OSDI (r = 0.290, P = 0.001), FTBUT (r = -0.195, P = 0.030), CFS (r = 0.352, P < 0.001), ME (r = 0.191, P = 0.033), and LMS (r = 0.370, P < 0.001). Conclusions: LMBFD may be a noninvasive, repeatable, reproducible, and efficient index for the quantitative evaluation of eyelid margin vascularity in the future. Translational Relevance: We demonstrated that SS-OCTA has the potential to evaluate the eyelid margin vascularity in MGD patients and guide future treatment strategies in clinics.

Development and content validity assessment of the Dry Eye Disease Questionnaire in patients with dry eye disease, meibomian gland dysfunction, and Sjögren's syndrome dry eye disease.

BACKGROUND: Dry eye disease (DED), Meibomian gland dysfunction (MGD), and Sjögren's syndrome dry eye disease (SS-DED) are eye dryness conditions that show significant overlap in various symptoms of ocular discomfort. The aim of this study was to qualitatively explore the patient experience and evaluate content validity of the newly developed Dry Eye Disease Questionnaire (DED-Q). METHODS: Semi-structured interviews were conducted with 61 US adults who reported experiencing ocular symptoms due to their physician-confirmed primary diagnosis of DED (n = 21), MGD (n = 20), or SS-DED (n = 20). The open-ended concept-elicitation phase was followed by cognitive debriefing (CD) of the DED-Q to evaluate participants' understanding and relevance of the instructions, items, response options, and recall periods. Interviews were also conducted with eight specialist healthcare professionals to assess clinical relevance of the concepts included. Verbatim interview transcripts were analyzed using thematic analysis in ATLAS.ti v8 software. RESULTS: A total of 29 symptoms and 14 impacts on quality of life were reported across participant interviews. Primary ocular symptoms reported included eye dryness (n = 61/61; 100%), eye irritation (n = 55/61; 90%), eye itch (n = 54/61; 89%), burning sensation (n = 52/61; 85%), and foreign body sensation (n = 51/61; 84%). The most impacted aspects of daily life were using digital screens (n = 46/61; 75%), driving (n = 45/61; 74%), working (n = 39/61; 64%), and reading (n = 37/61; 61%). CD findings showed most participants had good understanding of DED-Q items and confirmed most concepts were relevant to the lived experience of their condition. Aside from few minor changes to the items and examples to facilitate more accurate interpretation, the proposed instruction wording was modified for various symptom and impact modules to encourage participants to focus only on dry eye vision problems. CONCLUSIONS: This research identified multiple prevalent symptoms and impacts of DED, MGD, and SS-DED, most of which were similar across the conditions. The DED-Q was confirmed to be a content-valid PRO measure suitable for use in clinical studies to assess the patient experience of DED, MGD, and SS-DED. Future work will focus on evaluating the psychometric properties of the DED-Q for use as an efficacy endpoint in clinical trials.

Dry Eye Disease (DED), Meibomian Gland Dysfunction (MGD), and Sjögren's Syndrome Dry Eye Disease (SS-DED) are conditions related to dryness of the eye. There is no suitable patient-reported outcome (PRO) measure available for use across the three conditions. Interviews were conducted with 61 participants with any of the three conditions to understand the symptoms they experience and their impact on daily life. The findings were used to refine the content of a new PRO measure, the Dry Eye Disease Questionnaire (DED-Q). To evaluate the suitability of the DED-Q, participants were also asked to complete each item of the DED-Q during the interview and share their understanding of the item wording, response options and the recall period. Interviews were also conducted with eight healthcare professionals (HCPs). The main symptoms reported by the patients across three conditions were eye dryness, eye irritation, eye itch, burning sensation, and foreign body sensation. The symptoms caused difficulties in performing activities such as using digital screens, driving, working, and reading. Almost all participants demonstrated good understanding of the items on the DED-Q and found them to be relevant to their experience of their condition. The HCPs also confirmed that the concepts covered in the DED-Q were relevant to assess the participant experience across these conditions. Next steps will involve a more detailed analysis of the measurement properties of the DED-Q to confirm its usefulness in supporting primary or secondary endpoints in clinical trials.

Intraobserver Repeatability Assessment of the S390L Firefly WDR Slitlamp in Patients With Dry Eye Disease: Objective, Automated, and Noninvasive Measures.

OBJECTIVES: To assess the intraobserver repeatability of automated, objective, and noninvasive measures obtained with the S390L Firefly WDR slitlamp. METHODS: This cross-sectional study included 50 eyes of patients with dry eye disease with a mean age of 55.06±12.96 years. Three consecutively repeated measures of the following variables were obtained: first noninvasive break-up time (F-NIBUT), average noninvasive break-up time (A-NIBUT), tear meniscus height, tear meniscus area (TMA), nasal ciliary hyperemia (NCIH), temporal ciliary hyperemia (TCIH), nasal conjunctival hyperemia (NCOH), temporal conjunctival hyperemia (TCOH), upper loss area meibomian gland (U-LAMG), lower loss area meibomian gland (L-LAMG), upper meibomian gland dysfunction grade (U-MGD grade), and lower meibomian gland dysfunction grade (L-MGD grade). Intraobserver repeatability was estimated with coefficient of variation (CoV), intrasubject standard deviation (SD) (S w ), and Bland-Altman plots. RESULTS: All variables showed no statistically significant differences in the repeated-measures analysis except for L-MGD grade ( P =0.045). F-NIBUT and A-NIBUT obtained the highest CoV with an average value of 0.48±0.41 [0.02-1.00] and 0.34±0.25 [0.02-1.00], respectively. The remaining variables showed CoVs between 0.04±0.11 [0.00-0.43] and 0.18±0.16 [0.00-0.75]. A-NIBUT, TMA, NCOH, and L-LAMG obtained an S w of 2.78s, 0.21 mm 2 , <0.001, and 4.11%, respectively. Bland-Altman plots showed a high level of agreement between pairs of repeated measures. CONCLUSION: The S390L Firefly WDR slitlamp has moderate intraobserver repeatability for F-NIBUT and A-NIBUT, which suggests that F-NIBUT and A-NIBUT are tests with high variability. The remaining variables show satisfactory intraobserver repeatability.

Morphological and functional assessment of the tear film and meibomian glands in keratoconus.

PURPOSE: To evaluate morphological and functional state of the meibomian glands (MG) in keratoconus patients. METHODS: One hundred eyes of 100 keratoconus patients and 100 eyes of 100 age-matched control subjects were included into this study. Ocular Surface Disease Index (OSDI) scores, non-invasive break up time (NIBUT), findings of meibography, staining with fluorescein of the ocular surface, tear film break-up time (TBUT), and Schirmer I test were documented in all patients' eyes and control eyes and were compared between the groups . RESULTS: The mean TBUT and NIBUT were significantly lower, corneal staining and OSDI scores were statistically greater in the keratoconus group (p < 0.05). The mean meiboscore, partial gland, gland dropout and gland thickening scores for upper/lower eyelids were significantly greater in keratoconus patients than controls (p < 0.05). The NIBUT measurements significantly correlated with MG loss in upper/lower eyelids (p < 0.05). The severity of keratoconus seemed to correlate with meiboscore, partial gland, gland thickening scores in upper/lower eyelids. CONCLUSION: Our data suggests that corneal ectasia in keratoconus is related with alterations in ocular surface, tear film function and MG morphology. Early screening and treatment of MG dysfunction may improve ocular surface quality and allow better disease management in keratoconus patients.

Role of instrumental factors in Meibomian gland contrast assessment.

PURPOSE: Meibomian gland contrast has been suggested as a potential biomarker in Meibomian gland dysfunction. This study analysed the instrumental factors related to contrast. The objectives were to determine whether the mathematical equations used to compute gland contrast (e.g., Michelson or Yeh and Lin), impact the ability to identify abnormal individuals, to ascertain whether contrast between the gland and the background could be an effective biomarker and to assess whether using contrast-enhancement on the gland image improves its diagnostic efficacy. METHODS: A total of 240 meibography images from 40 participants (20 controls and 20 having Meibomian gland dysfunction or blepharitis), were included. The Oculus Keratograph 5M was used to capture images from the upper and lower eyelids of each eye. The contrast of unprocessed images and those pre-processed with contrast-enhancement algorithms were analysed. Contrast was measured on the eight central glands. Two equations for contrast computation were used, and the contrast both between glands and within a gland were calculated. RESULTS: Significant differences were found between the groups for inter-gland area in the upper (p = 0.01) and lower eyelids (p = 0.001) for contrast measured with the Michelson formula. Similar effects were observed when using the Yeh and Lin method in the upper (p = 0.01) and lower eyelids (p = 0.04). These results were obtained for images enhanced with the Keratograph 5M algorithm. CONCLUSIONS: Meibomian gland contrast is a useful biomarker of disease related to the Meibomian glands. Contrast measurement should be determined using contrast-enhanced images in the inter-gland area. However, the method used to compute contrast did not influence the results.

Dry Eye Subtypes in the Dry Eye Assessment and Management (DREAM) Study: A Latent Profile Analysis.

Purpose: Dry eye disease (DED) is a heterogeneous condition with poorly characterized subtypes. The DREAM study was a large multicenter randomized clinical trial that did not find omega-3 to be more effective than placebo in treating symptomatic DED. We performed secondary analysis of DREAM data to characterize DED subtypes and their omega-3 response. Methods: A total of 535 patients with moderate-to-severe DED were randomized to omega-3 or placebo treatment for one year. We used latent profile analysis to identify subtypes based on baseline Ocular Surface Disease Index, tear break-up time (TBUT), anesthetized Schirmer's test, corneal and conjunctival staining, and meibomian gland dysfunction (MGD). We evaluated omega-3's effect for each subtype using generalized linear regression. Results: Five clinically meaningful DED subtypes were identified. They differed significantly in sex (P < 0.001) and race (P = 0.02). Subtype 1 had the most severe DED signs yet milder symptoms and was associated with more Sjögren's syndrome (21%, P < 0.001). Subtype 2 had the mildest DED signs except MGD. Subtype 3 had the most severe symptoms, out of proportion to DED signs. Subtype 4 had relatively milder symptoms and MGD. Subtype 5 had severe MGD and TBUT and was associated with rosacea (29%, P = 0.04). Omega-3 was not significantly more beneficial than placebo for any subtype. Conclusions: Five clinically meaningful DED subtypes differed significantly in demographics, symptoms, signs, and systemic disease associations. Omega-3 was not significantly more effective than placebo for any subtype. Translational Relevance: T3 translational research identifying subtypes in the DREAM study can improve DED clinical classification and targeted management.

Assessment and Management of Dry Eye Disease and Meibomian Gland Dysfunction: Providing a Singapore Framework.

ABSTRACT: The purpose of this article is to provide a framework for general ophthalmologists in Singapore to manage dry eye. This framework considers the evidence in the literature as well as recommendations from expert panels such as the Tear Film & Ocular Surface Society Dry Eye Workshop II and the Asia Cornea Society Workgroup.This article covers the assessment of patient medical history and ask triage questions to identify local and systemic causes of dry eye disease (DED), excluding other possible causes, as well as the risk factors for DED and ocular surface inflammation. Evaluation of clinical signs to establish the diagnosis of DED and differentiation from other causes of irritable, red eyes are described. Tests for understanding the underlying disease processes and severity of DED are also presented.Management of dry eye should involve patient education and engagement. Information about the natural history and chronic nature of DED should be provided to improve long-term management of the disease and enhance compliance. Aggravating factors should be removed or lessened.We provide a guide to determine the most appropriate treatment (or combination of treatments) based on the severity and cause(s) of the disease, as well as the patient's needs and preferences. The aim of the management is to relieve ocular discomfort and prevent worsening of symptoms and signs, as well as to optimize visual function and minimize structural ocular damage. We also discuss the systematic follow-up and assessment of treatment response, as well as monitoring side effects of treatment, bearing in mind continuous support and reassurance to patients.

Assessment of tear film lipid layer thickness in patients with Meibomian gland dysfunction at different ages.

BACKGROUND: To evaluate the correlations between lipid layer thickness (LLT) and morphology and function of the meibomian glands in patients who were diagnosed as meibomian gland dysfunction (MGD) in different age groups. METHODS: Patients who have diagnosed as obstructive MGD were included in this prospective, cross-sectional study. Patients were divided into three groups: young (ages 20-39 years), middle-aged (ages 40-59 years), and older (aged ≥60 years). All patients completed an Ocular Surface Disease Index (OSDI) questionnaire and were evaluated for LLT, tear meniscus height (TMH), noninvasive tear film break-up time (NI-BUT) measurement, invasive TBUT (ITBUT), corneal fluoresceinstaining (CFS) score, eyelid margin abnormalities, Schirmer I test, and MG function and morphology, by using the Keratograph 5 and LipiView interferometer. RESULTS: Two hundred and nine patients (209 eyes) were included. The median LLT of all patient was 57 nm (IQR, 36.5 nm), and the LLT values were significantly different among the young group (median, 51 nm; IQR, 23.5 nm), middle-aged group (median, 59.5 nm; IQR 46.5 nm) and older group (median, 62 nm; IQR, 42.5 nm) (P = 0.033, Kruskal-Wallis test). In regression analyses controlling for confounder factors sex and MG loss, the LLT was positively correlated with age (ß = 5.539, P = 0.001). There was a negative correlation between LLT and MG dropout in the all (r = - 0.527, P < 0.001), young (r = - 0.536, P < 0.001), middle-aged (r = - 0.576, P < 0.001), and older (r = - 0.501, P < 0.001) groups. LLT was positively correlated with the MG expressibility in the all (r = 0.202, P = 0.003), middle-aged (r = 0.280, P = 0.044) and older (r = 0.452, p < 0.001) groups, but it was no statistical significance in the young group (r = 0.007, P = 0.949). CONCLUSIONS: The thickness of LLT was increased with age and significantly correlated with both MG secretion and morphology in middle-aged and older patients with obstructive MGD. LLT measurement is a useful screening tool for detecting obstructive MGD and age as an influential factor should be accounted for when interpreting the meaning of the LLT value. TRIAL REGISTRATION: NCT02481167 ; Registered 25 June, 2015.

Preliminary Assessment of Intense Pulsed Light Treatment on the Upper Eyelids for Meibomian Gland Dysfunction.

Objective: To conduct a preliminary assessment of the intense pulsed light (IPL) treatment on the upper eyelid. Background: IPL therapy is an effective therapy for meibomian gland dysfunction (MGD). The normal treatment region includes the skin below the lower eyelids and both temporal parts, but not the upper eyelid. Methods: Thirty patients with mid-to-severe dry eye disease caused by MGD were selected and randomly divided into two groups. Fifteen controls in group A received normal IPL treatment. Fifteen patients in Group B underwent additional IPL treatment on the upper eyelid. The change in noninvasive tear breakup time (BUT), Ocular Surface Disease Index (OSDI) questionnaire, patient satisfaction, and adverse events were measured and recorded at each visit, before each treatment. Results: The dry eye symptoms of the patients in both groups improved. The patients in group B had better recovery than those in group A: BUT (right eye: 11.6 ± 3.67 sec vs. 7.73 ± 1.99 sec; left eye: 12.73 ± 4.19 sec vs. 7.73 ± 1.40 sec), OSDI (8.87 ± 4.31 vs. 14.93 ± 3.47); patient satisfaction in group B remained good, but decreased in group A with prolonged treatment duration. No serious skin and eye complications were found in any patient. Conclusions: This study showed the patients who received IPL treatment on the upper eyelid experienced improved symptoms of MGD. A further long-term study should be conducted to increase our understanding of the effect of expanded IPL treatment.

Intense Pulsed Light for Meibomian Gland Disease: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the literature on the efficacy of intense pulsed light (IPL) on the eyelids in the management of meibomian gland disease (MGD) and meibomian gland-related ocular surface disease. METHODS: A literature search was last conducted on May 15, 2019, in the PubMed and Cochrane Library databases for English-language original research that assessed the effect of IPL on MGD in adult patients. Thirty-three articles were identified, and 12 studies were determined to be relevant to the criteria outlined for assessment. The panel methodologist (V.K.A.) assigned a level of evidence rating to each study; 4 studies were rated level II, and 8 studies were rated level III. Five studies had potential conflicts of interest and design limitations that affected interpretation of results. RESULTS: All studies documented improvement in clinically meaningful metrics, including tear breakup time (TBUT), corneal staining and eyelid margin measurements, meibum quality, meibomian gland expressability, ocular surface disease index (OSDI), and standard patient evaluation of eye dryness (SPEED) questionnaire scores. Side effects were relatively uncommon but included discomfort, cutaneous erythema, blistering, eyelash loss, and floaters; these were uniformly self-limited. CONCLUSIONS: Although methodological limitations and potential conflicts of interest in some studies raised concern, the existing body of literature demonstrates improvements in the signs and symptoms of MGD after IPL therapy.

Functional and Morphological Evaluation of Meibomian Glands in the Assessment of Meibomian Gland Dysfunction Subtype and Severity.

PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. STUDY POPULATION: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P = 0.006, P = 0.016) and obstructive MGD (P = 0.008, P = 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P < 0.01 and P < 0.006, respectively). CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss.

Assessment of Tear Functions in Patients with Acne Rosacea without Meibomian Gland Dysfunction.

Purpose: To evaluate the results of tear functions in acne rosacea. Methods: This prospective study includes 64 eyes of 32 acne rosacea patients without blepharitis and meibomian gland dysfunction and 90 eyes of 45 patients as control group. Tear functions of all were evaluated with ocular surface disease index (OSDI) questionnaire, and measurements of tear osmolarity were performed by using TearLab, Schirmer I tests without anesthesia and fluorescein tear break-up time (TBUT). Results: The mean Schirmer test result was 12.53 ± 6.54 in study group and 16.21 + 7.52 mm/5 min in control group (p = 0.28). The mean TBUT in study group was 8.21 ± 4.01 and in control group was 18.03 ± 6.45 s (p = 0.02). Mean tear osmolarity in study group was 304.77 ± 15.59and in control group was 275.23 + 28.52 mOsms/L (p = 0.03). Mean OSDI score in study group was 27.51 ± 16.73 and was 18.15 ± 7.05 in control group (p = 0.38). Conclusions: Our study demonstrated lower dry eye tests before the appearance of clinical signs of meibomian gland disease in acne rosacea.