Evaporative Dry Eye Disease Research Articles

The effect of thermo-mechanical device (Tixel) treatment on evaporative dry eye disease – A pilot prospective clinical trial

PurposeTo examine the effects of treatment with a thermomechanical skin device to the eyelid area on the clinical signs and symptoms of patients who suffer from dry eye disease (DED) secondary to meibomian gland dysfunction (MGD). MethodsForty patients aged 45 years or older with DED due to MGD were recruited. Both eyes (n = 80) of each patient received three treatments with the Tixel device (Novoxel®, Israel), with each treatment separated by a 2-week period. Treatment was applied across the upper and lower eyelids, with the same intensity, tip protrusion distance, and contact duration. Two additional follow-up visits were performed at 2-week intervals after treatment cessation. DED status was evaluated during each visit via SPEED II questionnaire, tear break-up time (TBUT), corneal staining score (CSS), MGD score, and frequency of lubricant use. Visual acuity (VA) was recorded during first and last visits. ResultsMean age was 64.3 ± 12.4 years and 72.5 % (n = 29) were female. 45 % (n = 18) had a history of blepharitis, 12.5 % (n = 5) had chalazia, and 17.5 % (n = 7) suffered from allergic conjunctivitis. Mean follow-up time was 2.1 ± 0.6 months. Comparing the first and last visits, all parameters showed significant improvement after Tixel treatment: mean SPEED II scores (16.5 ± 5.9 to 11.8 ± 6.7, p < 0.001), CSS (2.0 ± 1.3 to 0.5 ± 0.9, p < 0.001), TBUT (2.7 ± 0.8 s to 6.5 ± 2.2 s, p < 0.001), MGD score (2.7 ± 0.5 to 1.2 ± 0.4, p < 0.001), and rate of lubricant use (3.4 ± 2.4 per day to 1.9 ± 2.0, p < 0.001). VA also improved (0.10 ± 0.11 logMAR to 0.08 ± 0.10 logMAR, p < 0.05). No major side effects were observed. ConclusionsIn this pilot study Tixel treatment induced significant improvement of signs and symptoms among patients with DED due to MGD. Benefits persisted for at least one month. Further randomized controlled double-blinded studies are needed.

Autologous Platelet-Rich Plasma Drops for Evaporative Dry Eye Disease from Meibomian Gland Dysfunction: A Pilot Study.

PurposeTo evaluate the effects of autologous platelet‐rich plasma (PRP) drops for evaporative dry eye (EDE) disease from meibomian gland dysfunction (MGD).MethodsThis is a retrospective, consecutive case series of 20 eyes of 10 patients with EDE from MGD treated with PRP drops from November 2020 to November 2021 at a single outpatient clinic in Ontario, Canada. PRP drops were prepared from whole blood using a two-step centrifugation method. Patients were instructed to instill these drops six times daily for 4 weeks. The Canadian Dry Eye Assessment (CDEA) questionnaire score, patient subjective assessment (PSA) score, first and average non-invasive break-up times (f/a NIBUT), tear meniscus height (TMH), bulbar redness (BR), and meibograph grade (MG) were measured before and after the treatment course.ResultsSignificant improvements in dry eye symptoms and tear film parameters were observed. Dry eye symptoms significantly improved as per the CDEA (mean difference (MD) = −5.45, 95% confidence interval (CI) = [−7.9, −3.1], p<0.001) and PSA (MD = −2.6, 95% CI = [−3.9, −1.2], p<0.001). There were significant improvements in tear film parameters including fNIBUT (MD = 3.85s, 95% CI = [1.2, 6.8], p=0.006), aNIBUT (MD = −6.81s, 95% CI = [5.7, 11.1], p<0.001) and TMH (MD = 0.08, 95% CI = [0.003, 0.2], p=0.045). There was an improvement in conjunctival injection as measured by BR (MD = −0.36, 95% CI = [−0.4, −0.15], p=0.373). Five eyes experienced a one-grade improvement in MG (p=0.453), and none experienced worsening in MG with treatment. No temporary or permanent adverse effects were noted.ConclusionFour weeks of PRP therapy resulted in significant functional improvements in dry eye symptoms and tear film quality and quantity. Improvements in conjunctival injection and microstructural improvements in meibomian glands were also observed in some eyes. Overall, PRP is a promising treatment option for patients with EDE from MGD refractory to conventional treatments.

Prolactin Inducible Protein, but Not Prolactin, Is Present in Human Tears, Is Involved in Tear Film Quality, and Influences Evaporative Dry Eye Disease.

PurposeDecreased production of the aqueous component of the tear film is an important cause of the development of dry eye disease (DED). Tear production is influenced by hormones and hormone-like factors. Prolactin (PLR), a multifunctional pituitary gland hormone, is regularly present in the lacrimal gland of rats and rabbits. In humans, serum PLR concentration correlates with tear quality. To gain deeper insights of possible effects of PRL, prolactin receptor (PRLR) and prolactin inducible protein (PIP), we analyzed the three proteins in the human lacrimal apparatus and in reflex tears of healthy volunteers as well as patients suffering from DED.MethodsGene expression of PRLR and PIP was analyzed by RT-PCR in cadaveric human lacrimal gland and ocular surface tissues, immortalized human corneal epithelial cells (HCE and hTEPI) and human Meibomian gland epithelial cells (HMGECs). At the protein level, the expression and localization of PRL, PRLR and PIP in formalin-fixed paraffin sections of the lacrimal apparatus were studied by immunohistochemistry. In addition, tear fluid from DED patients and healthy volunteers was analyzed by ELISA to determine the concentration of PRL and PIP.ResultsRT-PCR analyses revealed gene expression of PRLR and PIP in human tissue samples of cornea, lacrimal glands, and eyelids, whereas only PIP, but not PRLR, was detectable in immortalized corneal epithelial cells. Immunohistochemistry revealed for the first time the expression and localization of PRL, PRLR, and PIP in human tissues of the lacrimal apparatus and at the ocular surface. PRL and PRLR were detectable in corneal epithelium, lacrimal glands, and Meibomian glands. Reflex tears from DED patients revealed significantly increased PIP concentrations, whereas PRL was undetectable in tears of DED patients and healthy volunteers.ConclusionPRL, PRLR, and PIP are found in the lacrimal apparatus and on the ocular surface. PIP, but not PRL, is present in human tears and appears to be involved in the physiology of tear film quality. Our clinical data revealed that PIP may affect tear quality, but further functional analyses are needed to fully elucidate the effects of PRL and PIP-associated factors in tear secretion as well as in the connection of DED.

Latest developments on meibomian gland dysfunction: Diagnosis, treatment and management

Background: Meibomian gland dysfunction (MGD) is one of the leading causes of evaporative dry eye disease and one of the most common ophthalmic conditions found in clinical practice. Meibomian gland dysfunction tends to be overlooked because its signs and symptoms do not cause blindness. Meibomian gland dysfunction is characterised by the obstruction of the meibomian gland terminal ducts resulting in tear film instability.Aim: The purpose of this article was to provide an update on MGD’s diagnosis and treatment.Method: A literature review was conducted using search engines such as Google Scholar, Medline and ScienceDirect databases. Keywords such as MGD diagnosis and management and treatment of MGD were used to search the databases.Results: A total of 44 relevant papers were reviewed. These papers were then curated to include only those concerning diagnosis of meibomian gland dysfunction, treatment of meibomian gland dysfunction and management options of meibomian gland dysfunction. The references of individual papers from the curated results were checked to yield a further 13 papers.Conclusion: Meibomian gland dysfunction is not a single entity but is multifactorial in origin; however, our understanding of the condition is evolving rapidly because of newer imaging technology. There is no gold standard treatment option for MGD, but many options are available that include medications and other procedures.

The effect of day-long mask wearing on non-invasive break-up time

PurposeThis study aimed to investigate the effect of day-long face mask wearing on non-invasive tear break-up time (NI-BUT) in health care staff due to working schedules.MethodsSeventy-four right eyes of 74 participants were included in the study. Participants completed the Ocular Surface Disease Index (OSDI) questionnaire, and NI-BUT measurements were performed between 08.30–09.00 and 16.30–17.00 h. Participants with an initial NI-BUT measurement below 17 s were classified as group-1, and those over 17 s were classified as group-2. NI-BUT changes during the day and correlation to age, gender, and OSDI results were evaluated.ResultsThirty-eight women and 36 men, with a mean age of 30.9 ± 8.5 years, were included in the study. The mean OSDI score of the participants was 28.6 ± 17.1. NI-BUT means of group-1 at baseline and 8th hour were 11.4 ± 3.3 and 7.9 ± 3.6 s, respectively, and the mean NI-BUT at the 8th hour was statistically significantly lower than the baseline (p < 0.0001). Also, 24.2% (8 people) of those in group-2 had the 8th-hour NI-BUT value fallen into the measurable range (below 17 s). No significant correlation was found between the decrease in NI-BUT value and age, gender, and OSDI (p = 0.08, p = 0.3, and p = 0.2, respectively).ConclusionThe use of face masks throughout the day leads to a significant reduction in NI-BUT, regardless of age, gender, and OSDI score. Prolonged use of face masks should be considered as a risk factor for evaporative dry eye disease.

A Water-Free Omega-3 Fatty Acid Eye Drop Formulation for the Treatment of Evaporative Dry Eye Disease: A Prospective, Multicenter Noninterventional Study.

Purpose: NovaTears®+Omega-3 is a water-free eye drop solution with non-animal-derived omega-3 fatty acids. It allows to supplement omega-3 fatty acids directly in the tear film of patients with dry eye disease (DED). This post-market clinical follow-up (PMCF) study evaluated for the first time the effects on clinical signs and patient symptoms of DED, and safety and tolerability of NovaTears+Omega-3 (0.2%) eye drops, when used in accordance with its approved label. Methods: A prospective, multicenter, single-arm, uncontrolled, open-label observational cohort study was performed in patients suffering from symptoms of evaporative DED. Patients were treated 4 times daily bilaterally according to the instructions for use for 8 weeks, and standard of care clinical end points were assessed at baseline and follow-up. The trial was conducted at 2 investigational sites in Germany, Europe. Results: Thirty-six patients were included and 33 completed the study. NovaTears+Omega-3 (0.2%) showed clinically and statistically significant improvements in various clinical signs, such as total corneal staining, tear film break-up time, and Meibomian gland dysfunction (MGD) score, as well as in symptoms measured by Ocular Surface Disease Index (OSDI©) and visual analog scales over the 8-week treatment period with change from baseline P values all <0.0001. No worsening of any safety parameter (intraocular pressure, slit-lamp examination, visual acuity) was observed, and no adverse event was reported throughout the study. Conclusions: In this observational PMCF study, NovaTears+Omega-3 was safe and well tolerated. Treatment over an 8-week period resulted in significantly improved clinical signs and subjective symptoms in patients with evaporative dry eye. The study was registered at www.clinicaltrials.gov (NCT04521465).

The Efficacy of Clinical Tests to Diagnose Evaporative Dry Eye Disease Related to Meibomian Gland Dysfunction.

Objectives To determine the efficacy of widely available subtype clinical tests to characterize evaporative dry eye disease (EDED) related to meibomian gland dysfunction (MGD) compared to normal and to validate those clinical cut points in an independent sample. Methods A diagnostic accuracy study (52 subjects), an investigator-masked study, was followed by a larger independent sample (364 subjects) analysis to confirm efficacy in normal and EDED subjects. All subjects were 18 years of age and older and were classified using a battery of clinical tests for dry eye that included symptoms, tear meniscus height, tear stability, ocular staining, evaporative-specific tests, and the Schirmer I test. Results Normal (nondry eye; n = 26) and EDED (n = 26) subjects completed the efficacy study. The global tests of tear breakup time, staining, and symptoms all produced AUCs ≥ 0.70, representing acceptable discrimination. EDED-specific tests of eyelid marginal signs, gland secretion quality, and gland loss did not demonstrate acceptable test efficacy or differences between normal and EDED subjects. In a larger, independent sample of normal and EDED subjects, gland secretion quality and eyelid marginal score achieved acceptable diagnostic levels: AUCs of 0.789 (CI: 0.734–0.844) and 0.729 (CI: 0.648–0.810), respectively, but not lipid interferometry grade or lower eyelid gland dropout estimated using meiboscopy. Conclusions Meibomian gland secretion quality is an efficient and useful functional indicator in EDED and should be incorporated into core outcome sets for this dry eye subtype.

Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction

Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3β-hydroxyl-steroid dehydrogenase (3β-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3β-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3β-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3β-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction.

Once-Daily Topical Phosphosulindac Is Efficacious in the Treatment of Dry Eye Disease: Studies in Rabbit Models of Its Main Clinical Subtypes.

Purpose: Dry eye disease (DED) is classified as aqueous deficient, evaporative, or mixed. We investigated the therapeutic effect of the novel anti-inflammatory drug phosphosulindac (PS) in rabbit models of DED encompassing its pathogenesis, and its transition to chronicity.Methods: We treated three rabbit models of DED with PS (hydrogel formulation) or vehicle topically applied 1 × /day. We induced aqueous-deficient DED (acute and chronic) by injecting Concanavalin A into lacrimal glands; evaporative DED by injecting into the upper eyelid inactivated Mycobacterium tuberculosis in complete Freund's adjuvant; and mixed DED through desiccative stress, induced by holding open the eye for 3 h. We determined corneal sensitivity, tear break-up time (TBUT), Schirmer's tear test (STT), tear osmolality, and fluorescein staining of the ocular surface.Results: PS reversed all abnormal DED parameters. In acute DED, PS dose dependently normalized corneal sensitivity and tear osmolality; and improved TBUT, STT, and fluorescein staining. PS normalized corneal sensitivity and improved all other parameters in chronic aqueous-deficient DED. In evaporative DED, PS normalized corneal sensitivity and improved TBUT and fluorescein staining (osmolality and STT were not significantly changed in this model). In the desiccative stress model, PS improved TBUT and fluorescein staining but had no effect on STT or tear osmolality.Conclusions: PS rapidly reversed almost all DED parameters in its three subtypes. The normalization of the suppressed corneal sensitivity suggests the possibility of marked symptomatic relief by PS. The hydrogel formulation allows once-daily dosing. PS merits further development as a potential treatment for DED.

Review of the Literature on Existing Management of Dry Eye Disease

Dry eye disease (DED) is a multifactorial disease in which the tear film’s homeostasis is lost, along with other ocular symptoms such as tear film instability and high osmolarity, neurosensory abnormalities, and ocular surface inflammation and damage. DED is a condition of lacrimal apparatus which is responsible for tear production. The tear film is a mixture of mucin, aqueous (water and solutes like NacI, sugar, urea, proteins,), lipids secreted by goblet cells, lacrimal glands, and meibomian glands, respectively. It keeps the eye moist, provides oxygen to the cornea, and has antibacterial properties. The lipid layer prevents the evaporation of the aqueous. DED is categorized into (i)Aqueous-tear deficiency, characterized by a deficiency of lacrimal glands to secrete tears, (ii)Evaporative DED, associated with increased tear loss by evaporation because there is a deficiency of the meibomian glands. The mechanism of DED might be loss of tear through evaporation or insufficient aqueous production or a combination of the two. DED is a widespread eye problem, which is often left untreated. It causes irritation, itching, dryness, foreign body sensation, and discomfort; severe case causes conjunctival congestion, keratinization, erosion of the corneal epithelium, and plaque formation. If left Univision- threatening vision-threatening, leading to complications like corneal ulceration and perforation. Various clinical tests are used to diose DED, including tear breakup time, tear osmolarity, Schirmer test, Rose Bengal staining, and expression of inflammatory markers. There is no cure for DED at present. The following modalities are used for its treatment:&#x0D; &#x0D; use of punctual and canalicular plugs,&#x0D; artificial tear products like polyethylene glycol/propylene glycol with guar HP,&#x0D; consuming food rich in omega-three fatty acids, antioxidants zeaxanthin, and lutein,&#x0D; Use of anti-inflammatory drugs, mucolytics, secretagogues.&#x0D; Reducing or avoiding mild risk factors like prolonged reading, prolonged use of contact lenses, excessive screen time, etc.&#x0D; Treatment of causative disease.&#x0D; &#x0D; Appropriate management and establishing reasonable patient expectations are necessary to ensure patient satisfaction and adherence to the treatment.

Clinical and Molecular Outcomes After Combined Intense Pulsed Light Therapy With Low-Level Light Therapy in Recalcitrant Evaporative Dry Eye Disease With Meibomian Gland Dysfunction.

Dry eye disease (DED) is a leading cause of ocular morbidity worldwide. This study evaluates the effects of combined light therapy [intense pulsed light (IPL) and low-level light therapy (LLLT)] on clinical and molecular outcomes in evaporative DED with meibomian gland dysfunction (MGD). This prospective study evaluated 94 eyes (47 subjects) with chronic MGD treated with combined light therapy. Patients underwent a detailed evaluation of MGD and DED using the Ocular Surface Disease Index, dry eye tests-tear breakup time and Schirmer test, ocular surface staining, meibomian gland expressibility scoring, and meibography. Patients underwent a single session of combined light therapy (IPL + LLLT treatment) using the Eye-light device. All these tests were repeated at 3 and 6 months after treatment. Tear fluid and ocular surface wash samples were collected from a subset of patients before and after treatment for cellular and secreted immune factor profiling by flow cytometry. Combined light therapy (IPL + LLLT) demonstrated a marked improvement in the clinical metrics studied. Three months after treatment, Ocular Surface Disease Index showed a significant reduction in 95.6% ( P < 0.0001), tear breakup time increased in 72.3% ( P < 0.0001), and meibomian gland expressibility scoring increased in 80.8% ( P < 0.0001) of the eyes. These effects were observed to be sustained during the 6-month follow-up visit. Significant ( P < 0.05) reduction in tear fluid levels of interleukin-1β, interleukin-17F, and MMP9; MMP9/TIMP1 ratio; and ocular surface B-cell proportions was observed. Combined light therapy shows promising results in patients with chronic MGD and DED, even in recalcitrant cases. Clinical and molecular factor alterations support the improved symptomatology and reduced inflammation.

Periplocin ameliorates mouse age-related meibomian gland dysfunction through up-regulation of Na/K-ATPase via SRC pathway

Age-related meibomian gland dysfunction (MGD) is the main cause of evaporative dry eye disease in an aging population. Decreased meibocyte cell renewal and lipid synthesis are associated with age-related MGD. Here, we found an obvious decline of Ki67, ΔNp63, and Na+/K+ ATPase expression in aged meibomian glands. Potential Na+/K+ ATPase agonist periplocin, a naturally occurring compound extracted from the traditional herbal medicine cortex periplocae, could promote the proliferation and stem cell activity of meibocyte cells in vitro. Moreover, we observed that periplocin treatment effectively increased the expression of Na+ /K+ ATPase, accompanied with the enhanced expression of Ki67 and ΔNp63 in aged meibomian glands, indicating that periplocin may accelerate meibocyte cell renewal in aged mice. LipidTox staining showed increased lipid accumulation after periplocin treatment in cultured meibomian gland cells and aged meibomian glands. Furthermore, we demonstrated that the SRC pathway was inhibited in aged meibomian glands; however, it was activated by periplocin. Accordingly, the inhibition of the SRC signaling pathway by saracatinib blocked periplocin-induced proliferation and lipid accumulation in meibomian gland cells. In sum, we suggest periplocin-ameliorated meibocyte cell renewal and lipid synthesis in aged meibomian glands via the SRC pathway, which could be a promising candidate for age-related MGD.

Deciphering the Action of Perfluorohexyloctane Eye Drops to Reduce Ocular Discomfort and Pain.

Perfluorohexyloctane (F6H8) eyedrops have been recently introduced in Europe as a product to treat dry eye disease, based on its ability to reduce tear film instability in Meibomian gland dysfunction and evaporative dry eye disease, although its mechanism of action is still unknown. In the present pilot study, we evaluated the effects of the ocular instillation of a single drop of commercial F6H8 eyedrops in 20 healthy humans (9 women/11 men), measuring: (a) Corneal surface temperature (CST) from infrared video images; (b) tear volume using phenol red threads; (c) blinking frequency; and (d) ocular surface sensations (cold, dryness, pricking, foreign body, burning, itching, gritty, eye fatigue, watering eyes, and light-evoked discomfort sensations; scored using 10 cm Visual Analog Scales), before and 5–60 min after F6H8 or saline treatment. CST decreased and tearing and blinking frequency increased significantly after F6H8 but not after saline solution. When applied unilaterally, CST decreased only in the F6H8-treated eye. No sensations were evoked after F6H8 or saline. The corneal surface temperature reduction produced by topical F6H8 does not evoke conscious ocular sensations but is sufficient to increase the activity of corneal cold thermoreceptors, leading to an increased reflex lacrimation and blinking that may relieve dry eye condition thus reducing ocular discomfort and pain.

Comparative of meibomian gland morphology in patients with evaporative dry eye disease versus non-dry eye disease

Many recent studies have showed that morphological changes are one of the key signs of meibomian gland disease (MGD). These changes can be seen even before symptom onset, potentially underestimating the prevalence of MGD; however, until now, there is no conclusive information about the impact of meibomian gland (MG) morphology in tear film physiology and disease. This study aimed to investigate the prevalence of anatomical and morphological MG alterations between patients with evaporative dry eye disease (DED) and healthy controls. Retrospective chart review of seventy-five patients with evaporative DED and healthy individuals who had dry eye assessments included Ocular Surface Disease Index questionnaire, meibum quality, meibum expressibility, lid margin abnormality, ocular staining, non-invasive tear film break-up time, and meibography. We did not find significant differences in MG alterations in the upper lid between healthy and DED subjects. Patients with evaporative DED presented MG alterations in the lower lid more frequently than healthy subjects (54.8 vs. 30.3%; p = 0.03). The presence of shortened glands was the only MG alteration that was more prevalent in the lower lid in dry-eye patients than in healthy subjects (p < 0.05). Subjects with evaporative DED presented more alterations in the lower lid than healthy subjects.

Focused ultrasound stimulation on meibomian glands for the treatment of evaporative dry eye.

Current treatments for meibomian gland dysfunction have several limitations, creating a necessity for other advanced treatment options. The purpose of this study is to determine the effectiveness of focused ultrasound stimulation for the treatment of dry eye disease caused by meibomian gland dysfunction. An in vivo study of nine Dutch Belted rabbits was conducted with focused ultrasound stimulation of the meibomian glands. A customized line-focused ultrasonic transducer was designed for treatment. Fluorescein imaging, Schirmer's test, and Lipiview II ocular interferometer were used to quantify outcomes from three aspects: safety, tear production, and lipid layer thickness. Both tear secretion and lipid layer thickness improved following ultrasound treatment. Five to 10 min after the ultrasound treatment, the mean values of lipid layer thickness increased from 55.33 ± 11.15 nm to 95.67 ± 22.77 nm (p < 0.05), while the mean values measured with the Schirmer's test increased from 2.0 ± 2.3 to 7.2 ± 4.3 (p < 0.05). Positive effects lasted more than three weeks. Adverse events such as redness, swelling, and mild burn, occurred in two rabbits in preliminary experiments when the eyelids sustained a temperature higher than 42°C. No serious adverse events were found. The results suggest that ultrasound stimulation of meibomian glands can improve both tear production and lipid secretion. Ultimately, ultrasound stimulation has the potential to be an option for the treatment of evaporative dry eye disease caused by meibomian gland dysfunction.

Novel Lipids of the Rabbit Harderian Gland Improve Tear Stability in an Animal Model of Dry Eye Disease.

Purpose: Instability of the tear film leads to evaporative dry eye disease (EDED), but the Harderian gland in some terrestrial vertebrates may produce novel lipids that stabilize the tear film and protect against dry eye. Here, the nonpolar lipids in the Harderian gland and tears of the rabbit but absent in human tears were identified and tested in preclinical studies to determine whether they could treat severe EDED. Methods: Lipids were identified primarily by atmospheric pressure chemical ionization mass spectrometry (MS) and fragmentation MS/MS. An identified lipid was synthesized and formulated as an emulsion and as a cyclodextrin (CD) clathrate. Following doses with test agents and controls, tear film breakup time (TBUT), tear production, corneal fluorescein staining, macrophage infiltration, and goblet cell survival were measured using standard tests at 0, 2 and 4 weeks in an animal model of EDED. Results: The lipid emulsion increased TBUT (P < 0.01) and tear production (P < 0.05), while it decreased corneal staining (P < 0.01) compared to controls. The lipid CD formulation increased TBUT (P < 0.05) and tear production (P < 0.05) but had no significant effect on the remaining test parameters. There were no differences in macrophage infiltration and conjunctival impression cytology scores between the formulations and their vehicle controls. Conclusions: Lipids in the rabbit Harderian gland and tears differ from those identified in human meibum and tears. These unique rabbit lipids may confer a protective effect against EDED and, as supplements to human tears, fulfill a similar role.

Efficacy of five-flash intense pulsed light therapy technique in patients with meibomian gland dysfunction

ABSTRACT Clinical relevance Meibomian gland dysfunction is the main cause of evaporative dry eye disease and can lead to ocular discomfort and ocular surface damage. Early diagnosis and management of this condition can prevent its impact on patients ‘visual health and quality of life. Background In the last decade, intense pulsed light therapy (IPL) has been introduced as a therapeutic option for patients with meibomian gland dysfunction (MGD). Various treatment modalities and protocols have been reported to increase the efficacy of this technique. This study aimed to assess the efficacy of a novel five-flash IPL technique in combination with home-based therapy and to compare it with conventional home care alone in patients with MGD. Methods In a randomised controlled trial, 100 symptomatic MGD patients were enrolled. The treatment group underwent three sessions of a five-flash IPL therapy. For all participants, eyelid warming, lid hygiene and lubricant therapy was prescribed. Ocular surface parameters were compared for control and treatment groups. Results Ocular Surface Disease Index (OSDI), non-invasive keratograph tear break up time (NIKBUT), fluorescein TBUT, MG expressibility, meibum quality and tear osmolarity were improved at follow up visits in both groups (p < 0.05). On day 75, NIKBUT was significantly higher in the IPL group (p = 0.045). The IPL treatment effect was not statistically significant (p > 0.05), except for bulbar and limbal hyperaemia (p = 0.02 and p = 0.02). In both groups, younger patients showed more improvement in NIKBUT (p = 0.02, r = −0.32; p < 0.001, r = −0.52). Conclusion IPL therapy combined with conventional home-based therapy, and home care alone are both effective for patients with MGD. IPL may have an additional role in the improvement of ocular hyperaemia.

Screening Evaporative Dry Eyes Severity Using an Infrared Image.

Background Dry eye disease (DED) is a multifactorial and one of the most common problems treated in an ophthalmic outpatient clinic. Due to the variability in presentation, diagnosis of DED consists of a combination of subjective and objective clinical tests. The purpose of this study was to assess the effectiveness of a handheld smartphone-based infrared thermal (IRT) camera for screening symptomatic evaporative DED. Methods This observational sex-matched control study assessed IRT images of 184 right eyes (46 normal and 138 DED) of 184 participants. Evaporative DED was assessed using noninvasive tear breakup time, fluorescein staining, and the Chinese version of the ocular surface disease index (C-OSDI) questionnaire and categorized into their respective dry eye symptomology group (none, mild, moderate, or severe). The ocular surface temperature (OST) at 8 anatomical regions of interest (ROI) (nasal conjunctiva, nasal limbus, nasal cornea, central cornea, inferior cornea, temporal limbus, temporal cornea, and temporal conjunctiva) were measured and compared using a handheld smartphone-based IRT camera. The effectiveness of these 8 ROIs OST in detecting varying severity of DED was evaluated in terms of correlations with severity of DED and their area under the curve (AUC). Results OST at the 8 anatomical ROI was significantly higher in DED participants than in the non-DED group (p < 0.05) except for inferior cornea, temporal limbus, and temporal conjunctival regions (>0.05). Analyzing 8 anatomical ROIs revealed that the nasal limbus had the highest Pearson correlation with the severity of DED (0.64, p < 0.001). Additionally, the nasal limbus ROI achieved the highest AUC of 0.79 (CI: 0.73–0.85; p < 0.05), sensitivity, and specificity (0.96 and 0.91) when comparing its ability to discriminated DED vs. non-DED eyes. Conclusions Rather than a diagnostic tool, handheld smartphone-based IRT images can be considered as a rapid, noninvasive, and hygienic screening tool in discriminating DED and non-DED and potentially alleviating inconvenience experienced during conventional tests.

Alterations in corneal nerves in different subtypes of dry eye disease: An in vivo confocal microscopy study

PurposeTo evaluate corneal subbasal nerve alterations in evaporative and aqueous-deficient dry eye disease (DED) as compared to controls. MethodsIn this retrospective, cross-sectional, controlled study, eyes with a tear break-up time of less than 10 s were classified as DED. Those with an anesthetized Schirmer's strip of less than 5 mm were classified as aqueous-deficient DED. Three representative in vivo confocal microscopy images were graded for each subject for total, main, and branch nerve density and numbers. ResultsCompared to 42 healthy subjects (42 eyes), the 70 patients with DED (139 eyes) showed lower total (18,579.0 ± 687.7 μm/mm2 vs. 21,014.7 ± 706.5, p = 0.026) and main (7,718.9 ± 273.9 vs. 9,561.4 ± 369.8, p < 0.001) nerve density, as well as lower total (15.5 ± 0.7/frame vs. 20.5 ± 1.3, p = 0.001), main (3.0 ± 0.1 vs. 3.8 ± 0.2, p = 0.001) and branch (12.5 ± 0.7 vs. 16.5 ± 1.2, p = 0.004) nerve numbers. Compared to the evaporative DED group, the aqueous-deficient DED group showed reduced total nerve density (19,969.9 ± 830.7 vs. 15,942.2 ± 1,135.7, p = 0.006), branch nerve density (11,964.9 ± 749.8 vs. 8,765.9 ± 798.5, p = 0.006), total nerves number (16.9 ± 0.8/frame vs. 13.0 ± 1.2, p = 0.002), and branch nerve number (13.8 ± 0.8 vs. 10.2 ± 1.1, p = 0.002). ConclusionsPatients with DED demonstrate compromised corneal subbasal nerves, which is more pronounced in aqueous-deficient DED. This suggests a role for neurosensory abnormalities in the pathophysiology of DED.

Meibomian Gland Dysfunction: Intense Pulsed Light Therapy in Combination with Low-Level Light Therapy as Rescue Treatment.

Background and Objectives: Evaporative dry eye disease is frequently associated with meibomian gland dysfunction. Patients are often unhappy because of daily drops, care burden, and suboptimal conventional treatments. In this study, we assessed the efficacy of a novel device, the Eye-light®, a combination of intense pulsed light therapy and low-level light therapy, as a novel treatment for meibomian gland dysfunction and dry eye disease. Materials and Methods: This was a retrospective, single-center study carried out over a 6-week period, in which 22 eyes from 11 patients were included. Each patient received four combined light therapy treatment sessions, once weekly over 4 weeks. Patients underwent a clinical examination and filled out a standardized questionnaire to evaluate symptoms one week prior to treatment, and one week after the fourth session. Results: Combined light therapy improved several ocular surface outcome measures in our patients. This study demonstrates that this adjunctive treatment significantly improves the ocular surface and quality of life of patients with dry eye disease and meibomian gland dysfunction. Conclusions: Combined light therapy may be included in meibomian gland dysfunction treatment protocols as an adjunctive rescue treatment.