Sutureless Dehydrated Amniotic Membrane (Omnigen) Application Using a Specialised Bandage Contact Lens (OmniLenz) for the Treatment of Dry Eye Disease: A 6-Month Randomised Control Trial.

Background and Objectives: Dry Eye Disease (DED) is a chronic condition characterised by tear film instability and ocular surface disruption, significantly impacting patients' quality of life. This study aimed to provide top-level clinical evidence for the long-term efficacy of dehydrated amniotic membrane (dAM, Omnigen®) delivered via a specialised bandage contact lens (sBCL, OmniLenz) for managing moderate-to-severe DED. Materials and Methods: This randomised controlled trial (NCT04553432) involved 93 participants with moderate-to-severe DED, randomised to receive a 1-week bilateral treatment of either dAM (17 mm diameter with 6 mm central 'window') applied under a sBCL or sBCL alone. Participants were assessed at baseline and followed up at 1, 3, and 6 months post-treatment. Outcomes included changes in symptomatology, tear film and ocular surface measurements, and in vivo confocal microscopy imaging of corneal nerve parameters and corneal dendritic cell (CDC) counts. Results: The dAM-sBCL group demonstrated a 65% reduction in OSDI scores at 6 months (p < 0.001), with 88% of participants showing improvement at 1 month. Corneal staining was significantly reduced in both groups. dAM-sBCL provided significant improvements in corneal nerve parameters at 1 month, with sustained positive trends at 3 months. Additionally, dAM-sBCL significantly reduced mature CDC counts, suggesting an anti-inflammatory effect. Conclusions: Treatment with dAM-sBCL for just 1 week significantly and rapidly improved dry eye symptoms as well as ocular surface signs for at least 3 months. It also enhanced corneal nerve health while reducing activated/mature corneal inflammatory cell numbers, presenting a safe and promising new treatment for moderate-to-severe DED.

Appropriateness of Questionnaires for the Diagnosis and Monitoring Treatment of Dry Eye Disease.

Objectives: If questionnaires contributing to the diagnosis of dry eye disease are to be recommended as alternatives to existing questionnaires, they must be comparable, with similar repeatability and treatment sensitivity. Comparability was thus examined for three common dry eye questionnaires along with identifying the individual questions that most strongly predicted overall scores. Methods: Anonymised data (n = 329) collected via the Ocular Surface Disease Index (OSDI), 5-item Dry Eye Questionnaire (DEQ-5) and Symptom Assessment in Dry Eye (SANDE) questionnaires (including responses to individual questions) from consenting patients were drawn from real-world dry eye clinics/registries in the United Kingdom, Australia and New Zealand; at follow-up, normalised changes were evaluated in 54 of these patients. Treatment data were also analysed from a 6-month, randomised controlled trial assessing artificial tear supplement treatments with 43 responders and 13 non-responders to treatment identified. The questions extracted from the OSDI which form the abbreviated 6-item OSDI were also analysed. Results: The agreement between the questionnaires ranged from r = 0.577 to 0.754 (all p < 0.001). For the OSDI, three questions accounted for 89.1% of the variability in the total score. The correlation between the OSDI and OSDI-6 was r = 0.939, p < 0.001. For the DEQ-5, two questions accounted for 88.5% of the variance in the total score. Normalised treatment changes were also only moderately correlated between the questionnaires (r = 0.441 to 0.595, p < 0.01). For non-responders, variability was 7.4% with both OSDI and OSDI-6, 9.7% with DEQ-5, 12.1% with SANDE-frequency and 11.9% with SANDE-severity scale. For responders, improvement with drops was detected with a 19.1% change in OSDI, 20.2% in OSDI-6, 20.9% in DEQ-5, and 27.5%/23.6% in SANDE-frequency/severity scales. Conclusions: Existing commonly used dry eye questionnaire scores do not show high levels of correlation. The OSDI was the least variable of the questionnaires and while displaying a slightly lower treatment effect than either the DEQ or SANDE, it was more sensitive to detection of a treatment effect. The quicker-to-complete OSDI-6 exhibited essentially the same outcome as the OSDI, with similar variability and treatment sensitivity.

Bilateral Sutureless Application of Human Dehydrated Amniotic Membrane with a Specialised Bandage Contact Lens for Moderate-to-Severe Dry Eye Disease: A Prospective Study with 1-Month Follow-Up.

Purpose: To assess changes in symptoms and ocular surface signs following a bilateral sutureless treatment of dehydrated amniotic membrane (dAM) under a specialised bandage contact lens (sBCL) in patients with moderate-to-severe dry eye disease (DED). Patients and Methods: In this prospective pre-post interventional study, 35 patients diagnosed with moderate-to-severe DED, with an Ocular Surface Disease Index (OSDI) score >30 on current treatment, were enrolled. Assessments were conducted at baseline (day -30), after 30 days run-in with no additional treatment (day 0 - control), and 30 days post sBCL+dAM treatment (day 30 - treatment). Intervention involved two successive bilateral 4-5 day sutureless applications of dAM (17mm diameter, with a 6 mm central aperture, Omnigen® VIEW) under an 18mm sBCL (OmniLenz®). Symptomatology and ocular signs were measured using OSDI, Dry Eye Questionnaire-5 (DEQ-5), Symptom Assessment iN Dry Eye (SANDE), and other ocular surface health indicators including non-invasive breakup time, corneal and conjunctival staining, and lid wiper epitheliopathy length and width (LWE). Results: While symptomatology remained stable during the 30-day no-treatment run-in, 1-month post-dAM treatment, there was a significant reduction in OSDI scores (from 55.8 to 32.3, p<0.001), DEQ-5 (from 14.6 to 10.0, p<0.001), SANDE frequency (from 65.2 to 43.6, p<0.001), and SANDE severity (from 59.8 to 41.1, p<0.001). Additionally, there was a notable decrease in the width of LWE staining, from grade 2 (50-75% of the lid wiper) to grade 1 (25-50% of the lid wiper) (p=0.011). Conclusion: A bilateral 8-10-day treatment duration with dAM applied with sBCL demonstrated a 31 to 42% improvement in symptomatology and a decrease in ocular surface signs of mechanical stress. This innovative bilateral treatment approach offers a promising treatment modality for patients with refractory moderate-to-severe DED.

Optimising subjective grading of corneal staining in Sjögren's syndrome dry eye disease.

AIM: To assess whether smaller increment and regionalised subjective grading improves the repeatability of corneal fluorescein staining assessment, and to determine the neurological approach adopted for subjective grading by practitioners. METHODS: Experienced eye-care practitioners (n = 28, aged 45 ± 12 years), graded 20 full corneal staining images of patients with mild to severe Sjögren's syndrome with the Oxford grading scheme (both in 0.5 and 1.0 increments, globally and in 5 regions), expanded National Eye Institute (NEI) and SICCA Ocular Staining Score (OSS) grading scales in randomised order. This was repeated after 7-10 days. The digital images were also analysed objectively to determine staining dots, area, intensity and location (using ImageJ) for comparison. RESULTS: The Oxford grading scheme was similar with whole and half unit grading (2.77vs2.81,p = 0.145), but the variability was reduced (0.14vs0.12,p < 0.001). Regional grade was lower (p < 0.001) and more variable (p < 0.001) than global image grading (1.86 ± 0.44 for whole increment grading and 1.90 ± 0.39 for half unit increments). The correlation with global grading was high for both whole (r = 0.928,p < 0.001) and half increment (r = 0.934,p < 0.001) grading. Average grading across participants was associated with particle number and vertical position, with 74.4-80.4% of the linear variance accounted for by the digital image analysis. CONCLUSIONS: Using half unit increments with the Oxford grading scheme improve its sensitivity and repeatability in recording corneal staining. Regional grading doesn't give a comparable score and increased variability. The key neurally extracted features in assigning a subjective staining grade by clinicians were identified as the number of discrete staining locations (particles) and how close to the vertical centre was their spread, across all three scales.

Effect of meibomian gland morphology on functionality with applied treatment.

PURPOSE: To determine how Meibomian gland (MG) morphology affects MG function by means of gland expression with the effect of treatment. METHODS: Fifteen patients (aged 31.6 ± 13.1 years) from a dry eye clinic diagnosed with MG dysfunction had their 365 lower lid MGs visualised with a slit-lamp biomicroscopy. Using infrared meibography (Oculus K5m), MG length, width and tortuosity were objectively measured. Each MG was expressed and the meibum graded (0=clear fluid, 1=cloudy fluid, 2= particulate fluid, 3=inspissated, or 4 = no expression) to determine its functionality. Participants had functionality repeated each time following a sequence of a warm compress, debridement, and forcible expression after 5 min. RESULTS: Just over 10 % of complete length MGs gave clear expression, while about 5% did not express at all, with most expressed meibum being particulate in nature. In contrast, the majority of partial length glands gave inspissated expression (38 %), with 32 % not expressing at all. No MG of <10 % length expressed. MG gland length was correlated with gland expression (r=-0.507, p < 0.001) and MG tortuosity (r=-0.129, p < 0.001), but not MG width (r=-0.090, p = 0.167). Regardless of MG length, warm compress increased the quality of expression (p < 0.002). Debridement further improved expression in partial MGs (p = 0.003), but not forcible expression (p = 0.529). CONCLUSIONS: Length is the key functional morphology metric of lower lid MGs. Warm compress and massage increase the quality of expression in all, but the shortest glands and patients with partial length glands also benefit from debridement.

Clinical practice patterns in the management of dry eye disease: A TFOS international survey.

PURPOSE: To examine clinical management and prescribing patterns for dry eye disease (DED), in relation to severity and subtype, by eye care practitioners across the globe. METHODS: An online, anonymous cross-sectional survey (on Qualtrics) translated into 14 languages was distributed to eye care practitioners across the globe. The survey included six questions around the management of DED, in relation to severity and subtype. RESULT: The survey was completed by 1139 eyecare professionals (37% ophthalmologists and 58% optometrists) from 51 countries. Management varied significantly by continent and country (p < 0.01). The most commonly recommended management approaches, internationally, included general advice (87%), low (85%) and high (80%) viscosity-enhancing unpreserved lubricants and lid wipes/scrubs (81%). Some treatments were prescribed largely independently of severity (e.g. artificial tears and nutritional supplements) while oral antibiotics, punctal occlusion, topical anti-inflammatory/immunosuppressants, secretagogues, biologics, therapeutic contact lenses and surgical approaches were prescribed by more practitioners as severity increased. Essential fatty acids, lipid sprays/drops, lid hygiene, warm compresses, intense pulsed light therapy and antibiotics (topical or oral) were more commonly recommended for evaporative DED, while punctal occlusion, therapeutic contact lenses, secretagogues and biologics were more commonly recommended for aqueous deficient DED. CONCLUSIONS: DED management differs across continents and countries. A wide range of management strategies are utilised at each severity level and between subtypes. The survey results enable clinicians to benchmark their practice to that of their peers, indicate where further research is required to optimise patient management and inform industry on how best to target product development.

Effect of Eye Spray Phospholipid Concentration on the Tear Film and Ocular Comfort.

OBJECTIVES: To evaluate the effect of eye spray phospholipid concentration on symptoms and tear film stability. METHODS: High-concentration (Tears Again, Optima Pharma GmbH, Hallbergmoos, Germany) and low-concentration (Ocuvers, Innomedis AG, Germany) phospholipid eye sprays were sprayed onto the closed eyelids of 30 subjects (33.2±1.8 years; 20 women) in a multicentered, prospective, crossover study. Ocular comfort (visual analog scale) and noninvasive tear film stability (NIBUT) of each eye were evaluated before application (along with the Ocular Surface Disease Index), 10 min after application, and 30 min after application. RESULTS: Comfort (high concentration: 68.5±16.4 vs. low concentration: 70.7±14.5 phospholipid) and NIBUT (high concentration: 11.5±4.6 sec vs. low concentration: 11.2±6.0 sec phospholipid) were not different (P>0.3) between sprays before application, but comfort (by 12 points, P=0.001) and NIBUT (by 5 sec, P=0.016) were significantly better with a high-concentration phospholipid spray at both 10 min and 30 min time points than those with the low-concentration phospholipid spray. CONCLUSIONS: The liposomal eye spray with higher concentration of phospholipids significantly improved ocular comfort and tear film stability in contrast to the eye spray with lower concentration of phospholipids, hence practitioners need to choose an appropriate eye spray to maximize the patient benefit.

Dry eye disease is associated with retinal microvascular dysfunction and possible risk for cardiovascular disease.

PURPOSE: To explore the presence of microvascular endothelial dysfunction as a measure for early cardiovascular disease in individuals diagnosed with dry eye disease (DED) as compared to age-matched normal controls. METHODS: Systemic blood pressure, Body Mass Index, intraocular pressure, blood levels of glucose (GLUC), triglycerides, cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] as well as retinal and peripheral microvascular function were assessed in twenty-five 35-50 year olds with diagnosed with DEDa (using the TFOS DEWS II criteria) and 25 age and sex-matched controls. RESULTS: After controlling all the influential covariates, individuals diagnosed with DED exhibited significant lower retinal artery baseline (p = 0.027), artery maximum diameter (p = 0.027), minimum constriction (p = 0.039) and dilation amplitude (p = 0.029) than controls. In addition, the time to reach the vein maximum diameter was significantly longer in the DED patients than in normal controls (p = 0.0052). Only in individuals diagnosed with DED, artery maximum constriction correlated statistically significantly and positively with HDL-C blood levels (p = 0.006). Similarly, artery slopeAD correlated positively with T-CHOL and LDL-C (p = 0.006 & 0.011 respectively). Additionally, artery baseline diameter and maximum constriction were significantly and negatively correlated to T-CHOL/HDL-C ratio (p = 0.032 and p = 0.013 respectively) in DED individuals only. CONCLUSIONS: Individuals with positive diagnosis of DED exhibit abnormal retinal microvascular function and possible higher risk for CVD.

Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial.

PURPOSE: To assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED). METHODS: Ninety-nine participants fulfilling the TFOS DEWS II diagnostic criteria for DED (64% females; mean ± SD age, 44 ± 16 years) were enrolled in a prospective, multicentre, double-masked, parallel group, randomised controlled trial. Participants instilled lipid-based nanoemulsion drops or non-lipid-based aqueous drops for six months, at least four times daily. Symptomology, tear film and ocular surface characteristics were assessed at Days 0, 30, 60, 90, 120, 150 and 180. RESULTS: Sustained reductions in OSDI, DEQ-5, and SANDE symptom scores from baseline were observed from Day 30 onwards in both groups (all p < 0.05) and decreased superior lid wiper epitheliopathy grades from Day 60 onwards (all p ≤ 0.01). Improvements in non-invasive tear film breakup time, and sodium fluorescein and lissamine green staining scores followed from Day 120 onwards in both groups (all p < 0.05). Tear lipid layer grades increased from Day 90 onwards only with the lipid-based drops, and with significantly greater improvement in those with suboptimal lipid layer thickness at baseline (grade ≤3; p = 0.02). By Day 180, 19% of participants no longer fulfilled the diagnostic criteria for DED. CONCLUSIONS: Over a six-month treatment period, improvements in dry eye symptomology preceded tear film and ocular surface changes with regular use of both lipid and non-lipid-based artificial tear supplements. Both formulations addressed most mild-to-moderate forms of aqueous deficient and evaporative DED, while evaporative cases benefitted preferentially from lipid-based supplementation. This represents a first step towards mapping DED therapeutic strategies according to disease subtype and severity.

Efficacy of a novel water propelled, heating eye mask massager on tear film and ocular adnexa.

PURPOSE: To determine the effectiveness of the Aurai water propelled, heating Eye Massager (AEM) in managing dry eye disease and its effects on the ocular adnexa. METHODS: This prospective, randomised cross-over study enrolled 15 participants (aged 25.8 ± 5.45 years, 5 male). Participants wore a smart watch 24 h a day to track their sleeping cycle and heart rate for 4 weeks, using the AEM twice a day for 2 of those weeks. A cycle of 6 min of a controlled heat and vibration pattern in the morning and another cycle in the evening were applied with the AEM. Primary outcomes of symptomatology (Ocular Surface Disease Index (OSDI) and Symptom Assessment iN Dry Eye (SANDE)), tear film and ocular surface homeostasis markers (osmolarity, non-invasive breakup time (NIKBUT), tear meniscus height (TMH), lipid layer thickness and ocular staining) and safety measures (ocular redness and intraocular pressure), were assessed at baseline, after 2 weeks of AEM use and after 2 weeks of no treatment (in random-sequence). Sleeping tracking (ST) and heart rate/blood oxygen detection over these periods was also assessed. RESULTS: There was a significant change in OSDI score from 34.3 ± 19.5 at baseline to 18.8 ± 17.5 after treatment (p = 0.001) and also for the SANDE (5.7 ± 2.4 vs 3.7 ± 2.1; p = 0.001). Heart rate was not affected by treatment (p = 0.956), nor sleep pattern (p = 0.529), but this varied by day (p = 0.001). Tear film and ocular surface homeostasis, the ocular adnexia and safety measures were not affected by treatment (p > 0.05). CONCLUSION: The Aurai water propelled Eye Massager may reduce the severity of symptoms of dry eye, but there were no detectable effects on tear stability and ocular surface disease from two weeks use.