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Jonathan Lilley,1 Erin C O’Neil,1 Vatinee Y Bunya,1 Kennedy Johnson,1 Gui-Shuang Ying,2 Peiying Hua,2 Mina Massaro-Giordano1 1Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; 2Center for Preventive Ophthalmology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Mina Massaro-GiordanoDepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA, 19104, USATel +1 215-662-9393Email mina@pennmedicine.upenn.eduPurpose: To assess the efficacy and safety of an intranasal tear neurostimulator (ITN) device in Sjögren syndrome (SS) patients.Methods: This was a two-visit prospective, randomized, controlled, same-day crossover study in participants with SS. Inclusion criteria were assessed at a baseline screening visit and included an Ocular Surface Disease Index (OSDI) score ≥ 13, and a Schirmer with anesthesia ≤ 10 mm/5 min (in at least one eye), with a cotton swab stimulation induced increase of ≥ 4 mm in the same eye. Participants returned for the application visit, where they received intranasal and extranasal applications of the ITN in random sequence, separated by at least 60 min. Schirmer scores were measured in both eyes after each application and compared to baseline values. Generalized linear models were performed to compare the change in Schirmer scores from baseline, and generalized estimating equations were used to account for correlations from repeated measurements in the same eye and measurements from two eyes of the same patient.Results: Fifty-five participants were screened and 35 were enrolled (all female), ranging in age from 31 to 72 years (mean, 57 years). The baseline OSDI score ranged from 14 to 91 (mean, 50.5), and the baseline Schirmer score had a mean (SD) of 6.4 (3.5) ranging from 0 to 20 (mm/5min). Improvement in Schirmer scores was significantly greater for intranasal device application (13.5 mm/5min, 95% CI: 10.4, 16.5) compared to extranasal device application (0.8mm/5min, 95% CI: − 0.9, 2.4) (p< 0.0001). The effects of the intranasal device application were significant regardless of the participant’s baseline Schirmer score and systemic SS medication usage (p< 0.05).Conclusion: Intranasal application of the ITN device significantly increased tear production in a subset of SS patients compared to baseline and was more effective than extranasal application. While production of the ITN device was recently discontinued, our findings suggest that other therapies that neurostimulate the lacrimal function unit may be effective in a subset of SS patients.Keywords: Sjögren syndrome, intranasal tear neurostimulation, tear production

Abstract: The corneal epithelium, supplied by thousands of nerve endings, plays a substantial role in absorbing and distributing nutrients along the ocular surface. Many studies have explored the influence of various modalities in regulating tear production to manage corneal disorders and dry eye disease. These findings have highlighted the advantages of enhancing corneal nerve function and regeneration through neurostimulation, neural signaling, immunomodulation, topical medication application, and surgical reconstruction. The purpose of this narrative review article was to provide an overview of the current state of knowledge on this topic based on a PubMed database literature search for relevant animal and human studies investigating the modification of the trigeminal pathway to restore corneal nerve function and improve overall ocular health. Further investigation into this area of research is important to help guide new therapeutic targets for the prevention and development of treatments of corneal degeneration., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

This article examines the impact of eyelid margin diseases on tear film composition and associated ocular surface disorders. It highlights the prevalence of blepharitis and meibomian gland dysfunction, discussing risk factors and diagnostic considerations. Various therapeutic approaches, including eyelid hygiene, antibiotics, and innovative treatments, are explored. Emphasizing the chronic nature of these conditions, the article underscores the need for patient compliance. Overall, it provides a concise overview of eyelid-related issues and potential management strategies. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study is to evaluate the use of a varenicline solution nasal spray (VNS) for reducing the signs and symptoms of dry eye following laser in situ keratomileusis (LASIK). Methods: Subjects electing to undergo LASIK were randomized to VNS (study group) or placebo/vehicle (control group) and initiated treatment with the nasal spray twice daily 28 days prior to surgery with continued treatment for 84 days following LASIK. After initiation of treatment, subjects were seen on the day of surgery and postoperatively on Days 1, 7, 28, 84 (3 months) and 168 (6 months). The primary outcome measure was the mean change in NEI-VFQ-25, a 25-item dry eye questionnaire, from baseline to 3 months. The second primary outcome measure was the mean change in corneal fluorescein staining. Secondary outcome measures included evaluation of tear break-up time, Schirmer testing, tear osmolarity and eye dryness score (EDS). Results: Twenty subjects were enrolled in each group and successfully underwent LASIK. Both groups demonstrated an improvement in the National Eye Institute Visual Function Questionnaire (NEI-VFQ) at 3 months. The study group demonstrated improved corneal staining scores at months 1 and 3. Similarly, the study group demonstrated improvement in tear osmolarity scores versus the placebo group at the same time points. Although the study group was numerically greater than placebo for each time point for both corneal staining and tear osmolarity, the differences were not statistically significant for any primary or secondary outcome measures. Conclusion: VNS is a dry eye treatment option for patients following LASIK and may have potential benefit for patients hoping to avoid additional topical medications. The results were not statistically significant compared to placebo in this trial, and further investigation of the use of VNS following LASIK in a larger trial would be beneficial. Plain Language Summary: Laser in situ keratomileusis (LASIK) is a very successful refractive surgery option for patients hoping to reduce or eliminate their need for spectacles. Signs and symptoms of dry eye disease are very common after LASIK owing to the transection of corneal nerves that occurs during the procedure, and many patients are advised to manage it with frequent instillation of artificial tears. This study evaluated the use of a varenicline solution nasal spray, a recently introduced pharmacologic option that stimulates natural tear production through activation of the trigeminal nerve pathway. This is the first study to evaluate the use of the varenicline solution nasal spray in patients after refractive surgery and demonstrates that it could represent a favorable, ocular surface-sparing option for patients to minimize the signs and symptoms of dry eye following LASIK, a procedure known to trigger symptoms of dry eye disease. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this trial was to evaluate the safety and efficacy of OC-01 (varenicline solution), a nicotinic acetylcholine receptor agonist nasal spray, on signs and symptoms of dry eye disease., Methods: A phase 2b, multicenter, randomized, double-masked, vehicle-controlled trial (ONSET-1; NCT03636061) was performed. Patients were aged 22 years or older with a physician's diagnosis of dry eye disease and previous use of artificial tears were randomized 1:1:1:1 to control (vehicle nasal spray twice daily [BID]), OC-01 0.006 mg BID, OC-01 0.03 mg BID, and OC-01 0.06 mg BID. The primary end point was the change in the anesthetized Schirmer test score from baseline to day 28 in the study eye. The secondary end points included the change in the eye dryness score from baseline to day 28., Results: One hundred eighty-two patients were randomized. After 28 days, patients who received OC-01 0.03 or 0.06 mg showed a statistically significant improvement in tear film production relative to vehicle, with least squares mean differences from vehicle of 7.7 mm [95% confidence interval, 3.8-11.7; P < 0.001] with OC-01 0.03 mg and 7.5 mm (95% confidence interval, 3.4-11.6; P < 0.001) with OC-01 0.06 mg. Patients receiving OC-01 0.03 mg showed a significant reduction in the eye dryness score by day 28 versus vehicle (P = 0.021); those receiving the OC-01 0.06 mg dose showed a nonsignificant reduction versus vehicle. OC-01 administration was associated with sneezing (62%-84%) and cough (9%-25%); these were transient and predominantly mild in severity., Conclusions: OC-01 nasal spray administered BID at 0.03 and 0.06 mg resulted in significant improvements in signs and symptoms of dry eye disease, was well tolerated, and warrants further clinical investigation., Competing Interests: D. Wirta and G. L. Torkildsen have received research grant support from Oyster Point Pharma, Inc. D. A. Hollander is an employee of Ora, Inc. E. Bendert was an employee at Statistics Collaborative, Inc at the time the study was conducted. L. Zeng is a current employee at Statistics Collaborative, Inc. M. Ackermann is a board member at Oyster Point Pharma, Inc. J. Nau is an employee at and shareholder of Oyster Point Pharma, Inc. The remaining author has no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: To review the neuroanatomy and physiology of the basal and reflex tearing and present the available and developing therapies using the concept of neurostimulation in dry eye disease (DED)., Recent Findings: The most prevalent current DED treatments seek to supplement low tear volume and tear components or reduce inflammation. Neurostimulation is a unique approach gaining momentum in recent years, geared toward increasing the production of all basal tear components by stimulating the nerves responsible for producing the various tear components. The neuroanatomy of the lacrimal unit provides several possible access points to stimulate tear production through two arms of the sensory trigeminal nerves. Modes of stimulation include chemical or energy in electrical or magnetic form. Research thus far has shown that neurostimulation can achieve lacrimal, goblet cell, and meibomian gland stimulation. Subjectively it improves symptoms of DED. Clinically, neurostimulation has improved the signs and symptoms of DED by increasing basal tear production and tear volume., Summary: Neurostimulation using electrical, mechanical, or chemical means is a novel concept to increase tear production and was demonstrated to be an effective, safe, and well-tolerated method for managing DED., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to investigate the efficacy and safety of trigeminal parasympathetic pathway (TPP) stimulation in the treatment of dry eye. A comprehensive search for randomized clinical trials was performed in seven databases (MEDLINE, Embase, CENTRAL, etc.) up to 28 February 2023. After screening the suitable studies, the data were extracted and transformed as necessary. Data synthesis and analysis were performed using Review Manager 5.4, and the risk of bias and quality of evidence were evaluated with the recommended tools. Fourteen studies enrolling 1714 patients with two methods (electrical and chemical) of TPP stimulation were included. Overall findings indicate that TPP stimulation was effective in reducing subjective symptom score (standardized mean difference [SMD], -0.45; 95% confidence interval [CI], -0.63 to -0.28), corneal fluorescence staining (mean difference [MD], -0.78; 95% CI, -1.39 to -0.18), goblet cell area (MD, -32.10; 95% CI, -54.58 to -9.62) and perimeter (MD, -5.90; 95% CI, -10.27 to -1.53), and increasing Schirmer's test score (SMD, 0.98; 95% CI, 0.65 to 1.31) and tear film break-up time (SMD, 0.57; 95% CI, 0.19 to 0.95). Compared to inactive or low-activity stimulation controls, it has a higher incidence of adverse events. Therefore, TPP stimulation may be an effective treatment for dry eye, whether electrical or chemical. Adverse events are relatively mild and tolerable. Due to the high heterogeneity and low level of evidence, the current conclusions require to be further verified. [ABSTRACT FROM AUTHOR]

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Nasal implants have emerged as a pioneering technology for nasal drug delivery systems. These are breakthrough options made of biocompatible materials that are temporarily inserted into the nasal passages for both functional and cosmetic purposes. Drug-eluting nasal implants are beneficial for improving patient compliance, reducing the need for repeated drug administration, and achieving controlled release of therapeutic agents. This article offers a comprehensive insight into nasal implants and their applications, and addresses a patent perspective in the same context. Important considerations for clinically approved implants, such as Propel, Sinuva, Sinu-Foam, and Relieva Stratus, have also been discussed. [ABSTRACT FROM AUTHOR]

ENGLISH SUMMARY: Dry eye disease (DED) is characterized by ocular dryness, irritation and blurred vision and has a significant impact on the patient's quality of life. This condition can be particularly severe in patients with aqueous deficient dry eye disease (ADDE) due to Sjögren's syndrome (SS), an autoimmune disease that affects the lacrimal and salivary glands. Current treatments for ADDE are often limited to symptomatic relief. A literature review was conducted to explore the current surgical interventions used or tested in humans with ADDE (I). These interventions include procedures involving the eyelids and tear ducts, transplantation of amniotic membrane or salivary glands, injections around the tear ducts and cell‐based injections into the lacrimal gland (LG). Each treatment has its advantages and disadvantages; however, treating dry eyes in patients with SS presents a particular challenge due to the systemic nature of the disease. Moreover, there is a need for new therapeutic options. Mesenchymal stem cells (MSCs) are a type of stem cell that have shown promise in regenerating damaged tissue and reducing inflammation in various diseases. Previous studies in animal models have suggested that MSCs could be effective in treating ADDE. Thus, this thesis aims to investigate the safety and efficacy of injecting MSCs into the LG as a treatment option for patients with ADDE secondary to SS. The study also aims to see this treatment in light of existing and novel investigational treatment options. The clinical studies conducted for this thesis are the first of their kind in humans. MSCs derived from healthy donors' adipose tissue (ASCs) were cultured in a laboratory, frozen and thawed ready for use. In the safety study, we performed the first human trial involving the administration of a single injection of ASCs into the LG of one eye in seven patients suffering from severe ADDE (II). The primary objective was to test the safety of this treatment, while the secondary objective was to assess improvements in subjective and objective signs of dry eye. The results of the trial showed no serious side effects within 4 months of follow‐up after treatment. On average, there was a 40% reduction in dry eye symptoms assessed with the Ocular Surface Disease Index (OSDI) questionnaire. Additionally, in the treated eye, there was a significant decrease in tear osmolarity, an increase in tear film stability and an increase in tear production. To further investigate the efficacy of this treatment, our research group performed a clinical, randomized study aiming to compare the ASC injection into the LG with the injection of a vehicle (the excipient in which the ASCs are dissolved) and observation (no intervention) (III). The study involved 20 subjects receiving ASC injection, 20 subjects receiving vehicle injection and 14 patients being observed without intervention. The subjects were examined to assess the outcomes with a 12‐month follow‐up after treatment. Both intervention groups showed a significant reduction in subjective dry eye symptoms of approximately 40%. This improvement was evident at the 1‐week follow‐up and persisted until the 12‐month follow‐up. The observation group did not experience any change in OSDI score. The ASCs group exhibited a significant mean increase in non‐invasive tear break‐up time (NIKBUT) of 6.48 s (149%) at the four‐week follow‐up, which was significantly higher than that in the vehicle group (p = 0.04). Moreover, the ASCs group showed a significant increase in NIKBUT compared to that in the observation group at the 12‐month follow‐up (p = 0.004). In both the ASCs and vehicle group, a significant increase in Schirmer test scores at the 4‐month follow‐up and the 12‐month follow‐up was observed. In conclusion, this thesis contributes valuable findings with a new treatment option for patients with dry eye disease. Injection of ASCs into the LG was shown to be safe and to improve subjective dry eye symptoms and specifically the tear film stability in patients with ADDE due to SS. Compared to other treatment modalities of ADDE, this treatment has greater potential, as ASCs could potentially be used as an anti‐inflammatory therapeutic option for managing DED of other causes as well. RESUMÉ (DANISH SUMMARY): Tørre øjne, karakteriseret ved tørhedsfornemmelse og irritation af øjnene samt sløret syn, har en betydelig indvirkning på patientens livskvalitet. Denne tilstand kan være særligt alvorlig hos patienter med nedsat tåreproduktion (ADDE) som følge af Sjögrens syndrom (SS), en autoimmun sygdom, der påvirker tårekirtlerne og spytkirtlerne. Nuværende behandlinger for ADDE er ofte begrænset til symptomlindring. Vi gennemførte en litteraturgennemgang for at undersøge, hvilke nuværende kirurgiske behandlingsmetoder, der anvendes eller testes hos patienter med ADDE (I). Disse interventioner inkluderer procedurer, der involverer øjenlåg og tårekanaler, transplantation af amnionhinde eller spytkirtler, injektioner omkring tårekanalerne samt cellebaserede injektioner i tårekirtlen. Hver behandling har sine fordele og ulemper, men behandling af tørre øjne hos patienter med SS udgør en særlig udfordring på grund af sygdommens systemiske udbredning, og der er behov for nye behandlingsmuligheder. Mesenkymale stamceller (MSCs) er en type stamcelle, der har vist lovende resultater med hensyn til at regenerere beskadiget væv og reducere inflammation i forskellige sygdomme. Tidligere undersøgelser i dyremodeller har indikeret, at MSCs kan være en effektiv behandling af ADDE. Denne afhandling har til formål at undersøge sikkerheden og effekten af injektion af MSCs i tårekirtlen som en mulig behandling til patienter med ADDE som følge af SS. Afhandlingen sigter også mod at sammenligne denne behandling med andre eksisterende, kirurgiske behandlingsmuligheder af ADDE. Som led i dette projekt udførte vi de første kliniske forsøg af sin art i mennesker. MSCs fra raske donorers fedtvæv (ASCs) blev dyrket i et laboratorium, frosset ned og er optøet klar til brug. Det første mål var at teste sikkerheden ved denne behandling og sekundært at undersøge behandlingens effekt. For at undersøge dette modtog syv forsøgspersoner med svær ADDE én injektion med ASCs i tårekirtlen på det ene øje (II). Resultaterne af forsøget viste ingen alvorlige bivirkninger inden for fire måneders opfølgning efter behandlingen. I gennemsnit fandt vi yderligere en 40% reduktion i symptomer på tørre øjne vurderet med et spørgeskema, og en markant stigning i tåreproduktionen og af tårefilmens stabilitet i det behandlede øje. For yderligere at undersøge effekten af denne behandling udførte vi et klinisk, randomiseret forsøg med det formål at sammenligne injektion af ASCs i tårekirtlen med injektion af en kontrolopløsning (væsken, hvor stamcellerne var opløst) og observation (ingen intervention) (III). Studiet omfattede 20 forsøgspersoner, der modtog ASC‐injektion, 20 forsøgspersoner, der modtog injektion af kontrolopløsningen, og 14 forsøgspersoner i observationsgruppen. Forsøgspersonerne blev undersøgt med en opfølgningstid på 12 måneder efter behandling. Begge interventionsgrupper viste en betydelig reduktion på ca. 40% i subjektive symptomer på tørre øjne. Denne forbedring var betydelig allerede ved opfølgning efter en uge og varede ved 12 måneder efter behandling. Observationsgruppen oplevede ingen betydelig ændring i symptomer. ASCs gruppen viste desuden en signifikant stigning i tårefilmsstabiliteten (NIKBUT) på 6,48 sekunder (149%) ved opfølgning efter fire uger, hvilket var markant højere end efter injektion af kontrolopløsning (p = 0,04). Desuden viste ASCs gruppen en betydelig stigning i NIKBUT sammenlignet med observationsgruppen ved opfølgning efter 12 måneder (p = 0,004). Både injektion af ASCs og kontrolopløsning medførte en betydelig stigning i tåreproduktionen ved opfølgning fire måneder og 12 måneder efter behandling. Denne afhandling bidrager med vigtige resultater inden for en ny behandlingsmulighed af tørre øjne. Injektion af ASCs i tårekirtlen viste sig at være sikker, forbedrede subjektive symptomer på tørre øjne og øgede særligt tårfilmens stabilitet hos patienter med ADDE på grund af SS. Sammenlignet med andre behandlingsmuligheder for ADDE har denne behandling vist et stort potentiale. ASCs kan muligvis også bruges som en anti‐inflammatorisk behandling af tørre øjne af andre årsager i fremtiden. [ABSTRACT FROM AUTHOR]

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and extremely serious drug-induced dermatological disorders. The ocular surface condition at the early stage has been little studied and should contribute to novel perspectives in early and effective topical therapy of these diseases. The objectives of the study were to evaluate the acute phase of ocular surface involvement and histopathologic changes in patients with acute SJS/TEN. Methods: Ten patients with acute phase of SJS/TEN onset and eleven age- and sex-matched healthy volunteers were recruited. Ocular surface symptoms and signs, conjunctival impression cytology, and tear multi-cytokine were assessed. Results: Ocular surface objective signs were normal at the acute stage of SJS/TEN, while most patients have abnormal ocular surface subjective symptoms and meibomian gland secretion. Conjunctival impression cytology showed a significant decrease in goblet cell density and severe ocular surface squamous metaplasia in acute SJS/TEN patients. Tear multi-cytokine analysis showed all 21 pro- and anti-inflammatory cytokines all sharply elevated. Goblet cell density was significantly negatively correlated with tear C-X3-C motif chemokine ligand 1 (CX3CL1) and interleukin 13. Conclusions: Severe pathologic squamous metaplasia and inflammation onset in the ocular surface at the acute stage of the SJS/TEN, even if the ocular surface condition seemed basically normal with adequate systemic immunosuppressant and general supportive treatment. Early topical anti-inflammatory therapy should be carried out actively. [ABSTRACT FROM AUTHOR]

Objective: To characterize diagnostic findings, test-retest repeatability, and correlations among lacrimal tests in dogs of diverse cephalic conformations., Animal Studied: Fifty healthy dogs (25 brachycephalic, 25 nonbrachycephalic)., Procedures: A series of diagnostics were performed in each dog, allowing for a 10-minute interval between tests and repeating each test 24 hours later under similar conditions: corneal tactile sensation (CTS), strip meniscometry test (SMT), phenol red thread test (PRTT), endodontic absorbent paper point tear test (EAPPTT), Schirmer tear test-1 without (STT-1) or with nasolacrimal stimulation (NL-STT1), and Schirmer tear test-2 (STT-2)., Results: Mean ± SD test values were lower in brachycephalic vs. nonbrachycephalic dogs (except for SMT; 7.4 ± 2.0 mm/5 seconds vs 7.3 ± 2.4 mm/5 seconds), with statistically significant differences noted for CTS (1.8 ± 0.5 cm vs 3.4 ± 0.8 cm), PRTT (37.2 ± 4.0 mm/15 seconds vs 41.1 ± 5.5 mm/15 seconds), STT-1 (20.1 ± 3.4 mm/min vs 23.3 ± 5.7 mm/min), STT-2 (13.0 ± 3.4 mm/min vs 16.9 ± 3.9 mm/min), and NL-STT1 (23.2 ± 3.6 mm/min vs 27.1 ± 5.4 mm/min), and nonsignificant differences for EAPPTT (16.6 ± 2.7 mm/15 seconds vs 17.5 ± 2.9 mm/15 seconds). Nasolacrimal stimulation increased STT-1 values by 18% on average. Correlations among tests were generally weak to moderate (r < .70) except for a strong correlation between STT-1 and NL-STT1 (r = .83, P < .001). Test reliability was good although test-retest repeatability was generally poor to moderate, as depicted by low intraclass correlation coefficients (ICC ≤ 0.75) and wide 95% limits of agreement, except for CTS (ICC = 0.91)., Conclusions: Corneal sensitivity and aqueous tear secretion are lower in brachycephalic dogs. A comprehensive assessment of the ocular surface requires the combination of several diagnostic tests. The nasolacrimal reflex may provide a useful diagnostic and therapeutic tool in dogs., (© 2020 American College of Veterinary Ophthalmologists.)

Dry eye disease (DED) is a widespread, multifactorial, and chronic disorder of the ocular surface with disruption of tear film homeostasis as its core trait. Conjunctival goblet cells (CGCs) are specialised secretory cells found in the conjunctival epithelium that participate in tear film formation by secreting mucin. Changes in both the structure and function of CGCs are hallmarks of DED, and imaging assessment of CGCs is important for the diagnosis, classification, and severity evaluation of DED. Existing imaging methods include conjunctival biopsy, conjunctival impression cytology and in vivo confocal microscopy, which can be used to assess the morphology, distribution, and density of the CGCs. Recently, moxifloxacin-based fluorescence microscopy has emerged as a novel technique that enables efficient, non-invasive and in vivo imaging of CGCs. This article presents a comprehensive overview of both the structure and function of CGCs and their alterations in the context of DED, as well as current methods of CGCs imaging assessment. Additionally, potential directions for the visual evaluation of CGCs are discussed., (© 2024 Royal Australian and New Zealand College of Ophthalmologists.)

Dry eye disease (DED) is a complex multifactorial condition caused by loss of ocular surface homeostasis from quantitative and/or qualitative tear film deficiency. Schirmer tear test (STT) is often the only diagnostic test used to assess for DED in veterinary practice. STT is invaluable in the diagnosis and monitoring of quantitative tear film deficiency (i.e., keratoconjunctivitis sicca); however, it is not sufficient to optimize therapy and fully recognize other contributing factors for the disturbance in ocular surface homeostasis. The present work reviews diagnostic tests for assessing aqueous tear production in veterinary medicine, as well as the quality of tears, corneal epithelial barrier integrity, and the lacrimal functional unit. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a broad term that includes a diverse group of clinical disorders. Aqueous‑deficient dry eye (ADDE), a subtype of DED, is characterized by decreased tear production by the lacrimal gland. It can be seen in up to one‑third of individuals with DED and can be comorbid with a systemic autoimmune process or occur secondary to an environmental insult. Since ADDE can be a source of long‑term suffering and severe visual impairment, early identification and adequate treatment are imperative. Multiple etiologies can underlie ADDE, and it is critical to identify the underlying cause to not only improve the ocular health but also to improve the overall quality of life and well‑being of affected individuals. This review discusses the various etiologies of ADDE, highlights a pathophysiology‑based approach for evaluating underlying contributors, outlines various diagnostic tests, and reviews treatment options. We present the current standards and discuss ongoing research in this field. Through this review, we propose a treatment algorithm that would be useful for an ophthalmologist in diagnosing and managing individuals with ADD. [ABSTRACT FROM AUTHOR]

Dry eye disease is a prevalent, multifactorial disease characterized by loss of tear film homeostasis. A myriad of ocular therapeutics is commercially available and in development for personalized management of dry eyes. Recently, Varenicline solution nasal spray (VNS) received approval from the US Food and Drug Administration for the treatment of dry eyes. This review explores the current mainstay treatments for dry eyes and the role of VNS in addressing unmet needs in the treatment of dry eye disease. A PubMed and MEDLINE keyword search on Tyrvaya and Varenicline nasal solution spray was performed as a part of the inclusion criteria. Varenicline solution nasal spray has been shown to be well tolerated and demonstrated to provide clinically significant improvement in patients with dry eyes Treatment of dry eye disease with VNS may be most beneficial in patients with limited upper-body mobility, dexterity issues, tremors, and glaucoma. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a widespread and frequently reported multifactorial ocular disease that not only causes ocular discomfort but also damages the cornea and conjunctiva. At present, topical administration is the most common treatment modality for DED. Due to the existence of multiple biological barriers, instilled drugs generally exhibit short action times and poor penetration on the ocular surface. To resolve these issues, several advanced drug delivery systems have been proposed. This review discusses new dosage forms of drugs for the treatment of DED in terms of their characteristics and advantages. Innovative formulations that are currently available in the market and under clinical investigation are elaborated. Meanwhile, their deficiencies are discussed. It is envisioned that the flourishing of advanced drug delivery systems will lead to improved management of DED in the near future. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a multifactorial chronic condition with a broad spectrum of symptoms that can affect daily activities and quality of life. New treatment approaches that target more systematically distinct parts of the pathophysiology would present new potential to effectively regulate signs and symptoms of DED. In this review, a comprehensive list of device-based treatments has been provided, according to their mechanism of action. Given the variability and complexity of DED, adjuvant treatments should be considered as a boost for patients who do not respond to first-line therapy. Most of those devices primarily target meibomian glands, using heat or mechanical energy to restore normal meibum flow. Although several treatments have been discussed in this review, further studies are needed to identify new options, evaluate current therapies in randomized clinical trials more extensively, and identify which subtypes of DED could benefit from any given therapy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to demonstrate the effectiveness of Systane iLux, a thermal pulsation device, in patients with MGD, over 12 months post-single treatment. Methods: This is a post-hoc analysis of a previous prospective, assessor-masked, parallel-group, multicenter study (NCT03956225) that compared the effectiveness and safety of iLux with LipiFlow in subjects with MGD. The original study included subjects with meibomian gland score (MGS) ≤ 12 in lower eyelids, Impact of Dry Eye on Everyday Life-Symptom Bother (IDEEL-SB) module score > 16, and non-invasive tear break-up time (NITBUT) < 10 seconds. Subjects were randomized (1:1) to receive a single bilateral treatment of iLux or LipiFlow. In this post-hoc analysis, mean changes in MGS, NITBUT (first break-up; seconds), IDEEL-SB module score, and corneal staining, from baseline to 12 months were analyzed post-single treatment with iLux. Results: Data from 119 patients (n=238 eyes) treated with iLux were analyzed. The mean±SD age of the subjects was 58.4± 13.4 years, with majority being female (79.0%). MGS (mean±SD) for both eyes improved significantly from baseline to 12 months (OD [baseline: 6.9± 3.69; month 12: 22.8± 11.31; change: 15.9± 11.57, p< 0.0001]; OS [baseline: 6.4± 3.66; month 12: 23.0± 11.33; change: 16.7± 11.40, p< 0.0001]). Similarly, significant improvements were observed in NITBUT (OD [baseline: 5.2± 1.97; month 12: 7.0± 3.68; change: 1.9± 3.69, p< 0.0001]; OS [baseline: 5.6± 1.96; month 12: 7.9± 4.58; change: 2.3± 4.59, p< 0.0001]) and IDEEL-SB score (p< 0.0001). Corneal staining reduced significantly from baseline to 12 months (OD [baseline: 2.1± 2.96; month 12: 0.7± 1.56; change: − 1.4± 2.65, p< 0.0001]; OS [baseline: 2.1± 2.94; month 12: 0.7± 1.44; change: − 1.4± 2.75, p< 0.0001]). Improvements in MGS, NITBUT, IDEEL-SB module score, and corneal staining were seen as early as week 2, and at months 1, 3, 6, and 9 (all p< 0.001). Conclusion: A single treatment with iLux significantly improved clinical parameters of MGS, NITBUT, and corneal staining, and patient-reported symptom assessment with IDEEL-SB in patients with MGD over 12 months. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate OC-01 [varenicline solution nasal spray (VNS)] tear production and symptom outcomes in patients with dry eye disease by age, gender, race, ethnicity, and artificial tear use status. Patients and Methods: Adults ≥ 22 years of age diagnosed with dry eye disease, with Ocular Surface Disease Index score ≥ 23, corneal fluorescein staining score ≥ 2 in ≥ 1 region or ≥ 4 for all regions, and baseline Schirmer Test Score (STS) ≤ 10 mm, with no restrictions on eye dryness score (EDS). Efficacy was assessed using integrated data from ONSET-1 and ONSET-2 [vehicle control (VC), n=294; OC-01 VNS 0.03 mg, n=308]. Subgroups included age (≤ 55, 56− 65, > 65 years), gender (male, female), race (White, Black or African American), ethnicity (Hispanic or Latino, Not Hispanic or Latino), and artificial tear use (yes, no). Analysis of covariance models, with the covariates treatment, study site, and baseline severity measures, were used to calculate treatment−VC differences. Consistency of effect among subgroups was evaluated by conducting interaction tests. Results: Consistency of treatment effect across subgroups was observed for all endpoints, with P value for all treatment−subgroup interaction terms > 0.05. For % of patients with ≥ 10mm improvement in STS and least squares (LS) mean change from baseline in STS and EDS, there was improvement in tear production across demographic group categories. Artificial tear use did not change STS or EDS outcomes with OC-01 VNS. Conclusion: OC-01 VNS improved tear production and patient-reported symptom outcomes across a broad range of patients by age, gender, race, and ethnicity, and regardless of artificial tear use status at baseline. OC-01 VNS demonstrated a consistent benefit across an extensive range of patients with dry eye disease. [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease is characterized by a persistently unstable or deficient tear film causing discomfort or visual impairment. Varenicline is a small-molecule nicotinic acetylcholine receptor agonist recently approved for use as a preservative-free nasal spray (OC-01 [varenicline solution] nasal spray [OC-01 VNS]) to treat signs and symptoms of dry eye disease, but its effect on conjunctival goblet cells has not been studied. Methods: In this phase 2, single-center, vehicle-controlled study, patients aged 18 years or more with a diagnosis of dry eye disease and Ocular Surface Disease Index© score of at least 23 were randomized 2:1 to receive a 50-µL single dose of OC-01 0.06 mg VNS or vehicle nasal spray in each nostril. Image assessments for area and perimeter were performed pre and 10 min post treatment for goblet cells by in vivo confocal microscopy and for meibomian glands by infrared meibography. Non-parametric Wilcoxon signed-rank test compared pre- and post-treatment measurements for each treatment group. Treatment-emergent adverse events (TEAEs) were assessed. Results: The study randomized 18 patients (mean age 61 years); 6 received vehicle (3/6 [50%] female) and 12 patients received OC-01 VNS (11/12 [92%] female). OC-01 VNS treatment decreased mean goblet cell area (pre-treatment, 106.4 µm2; post-treatment, 67.6 µm2; p = 0.02) and perimeter (pre-treatment, 38.9 µm; post-treatment, 31.2 µm; p = 0.03) but not vehicle did not (p = 0.25). There were no significant changes in mean meibomian gland area with either treatment (p ≥ 0.05). All TEAEs were non-ocular, non-serious, and mild. Conclusions: This study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced conjunctival goblet cell area and perimeter, suggesting goblet cell degranulation and associated release of lubricating mucin. By activating the natural tear film, OC-01 VNS may provide benefits over topical medications. Trial Registration: ClinicalTrials.gov, NCT03688802. [ABSTRACT FROM AUTHOR]

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Dry eye disease (DED) affects up to one-third of the global population. Traditional therapies, including topical lubricants, have been employed with variable success in the treatment of DED. Recently, neurostimulation of the lacrimal functional unit (LFU) has emerged as a promising alternative therapy for DED. In this review, we describe the neuroanatomical and pathophysiological considerations of DED and the LFU that make neurostimulation a viable therapeutic alternative. We further detail the various neurostimulatory approaches taken thus far—from implanted stimulators to external devices to chemical neurostimulation. Existing studies reveal the strengths of the neurostimulatory approach in increasing tear volume and improving dry eye symptoms, but further studies are needed to elucidate its true potential in treatment of DED. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prevalence of meibomian gland dysfunction (MGD) among ophthalmic healthcare workers. Setting: A tertiary ophthalmic center. Design: Prospective, observational study. Methods: Forty-four volunteer ophthalmologists and ophthalmic nurses were recruited. Information including demographics, contact lens wear, history of refractive surgery and symptom score based on Standardized Patient Evaluation of Eye Dryness (SPEED) II Questionnaire for Dry Eye Disease/Ocular Surface Disease were recorded. Lipid layer thickness (LLT), meibomian glands dropout and dilation grades, and proportion of partial blinking were evaluated using an ocular surface interferometer with dynamic meibomian imaging (LipiView, Johnson & Johnson). Based on the chance of MGD, meibomian gland dropout and dilation, selected subjects also underwent treatment with a thermal pulsation system (LipiFlow, Johnson & Johnson) in one or both eyes. Results: Eighty-eight eyes of 44 volunteers were evaluated during the study period. The mean LLT was 60.0nm. Twenty-seven (61.4%) subjects had a 90% or high chance of MGD and their mean lower lid meibomian gland dropout and dilation grades were 1.2 and 1.7, respectively. Twenty-eight eyes of 16 volunteers received treatment with the thermal pulsation system. Following treatment, the mean LLT improved from 50.3nm to 61.0nm (Wilcoxon's signed rank test, p=0.001). Conclusion: Despite being more knowledgeable to MGD and more accessible to treatment, MGD is a highly prevalent condition among ophthalmic healthcare workers, with a 61.4% prevalence among the recruited subjects. This is similar to reported prevalence in Asian populations of up to 74.5%. Targeted therapy based on dynamic meibomian imaging is effective in improving both objective and subjective measures of MGD. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the effect of one TrueTear session on change in tear volume and symptoms of dryness and ocular pain. Methods Retrospective interventional case series of patients seen in a dry eye clinic. Seventy-five individuals underwent an ocular surface examination and one session of neurostimulation. Outcome measures included objective change in tear volume measured via phenol red test, and subjective change in sensations of dryness and ocular pain measured on a 0-10 Numerical Rating Scale. Results The mean age of the 75 individuals was 59±13 years, and the majority were male (73%). Intranasal neurostimulation increased tear volume (mean 13.40 ±8.00 mm, p<0.0005) and reduced intensities of dryness (mean -2.85±2.79, p<0.0005) and ocular pain (mean -1.48±2.41, p<0.0005 for both). However, these effects were independent of one another as change in symptom report did not correlate with change in tear volume (r=-0.13, p=0.25 for dryness; r=0.07, p=0.56 for pain). In a multivariable model, the strongest predictors for increased tear volume were lower baseline tear volume (standardised beta (β)=-0.50, p<0.0005) and absence of an autoimmune disease (β=-0.36, p=0.001) (R2=0.30). The strongest predictors for reduced dryness and pain scores were lower baseline dryness and ocular pain scores. No complications related to neurostimulation were noted. Conclusion Intranasal neurostimulation increased tear volume and reduced intensities of dryness and ocular pain, independently of one another. [ABSTRACT FROM AUTHOR]

Meibomian gland dysfunction (MGD) is frequently encountered by eye care practitioners. It is characterised by obstruction of the Meibomian glands and/or alterations in the consistency of glandular secretions. At present, no definitive treatment exists for this condition. The present meta-analysis was performed to assess the efficacy of intense pulsed light (IPL) therapy in the management of MGD. Databases including EMBASE, PubMed, Cochrane Central, MEDLINE and Google Scholar were systematically searched to identify clinical trials that assessed the efficacy of IPL in the treatment of MGD. Outcome measures were described as the standardized mean difference (SMD). The fixed- or random-effects model was selected for analysis based on the Cochrane I2 values representing heterogeneity. Publication bias was visually inspected using Begg's funnel plot. Data were synthesized from four randomized controlled trials (RCTs) comprising 122 subjects in the IPL group and 120 subjects in the control group. Pooled analysis indicated no statistically significant difference in the Standard Patient Evaluation of Eye Dryness (SPEED) scores between the two groups [SMD -0.16 (95% CI, -0.41 to 0.10)] but a significant increase in Non-Invasive Tear Break-Up Time (NIBUT) scores in the IPL group (SMD, 0.90; 95% CI, 0.40-1.40). To conclude, the results of the present study did not provide any conclusive evidence for the efficacy of IPL therapy in the management of MGD. The analysis indicated that IPL therapy may result in an improvement of objective NIBUT scores but has no effect on subjective SPEED scores. Given the limited number of studies performed to date, there is a requirement for more well-designed prospective RCTs with a larger sample size to provide further evidence on the efficacy of IPL therapy. [ABSTRACT FROM AUTHOR]