Dry Eye Disease Associated with Meibomian Gland Dysfunction: Focus on Tear Film Characteristics and the Therapeutic Landscape

Abstract

Meibomian gland dysfunction (MGD) is highly prevalent and is the leading cause of evaporative dry eye disease (DED). MGD is characterized by a reduction in meibum secretion and/or a change in meibum composition that results in the disruption of the tear film lipid layer and an increase in the tear film evaporation rate. Excessive evaporation causes tear film instability, desiccation, tear hyperosmolarity, inflammation, and apoptosis of ocular surface cells, resulting in a continuous cycle of DED. The primary treatment goal for DED associated with MGD is to restore the tear film lipid layer and decrease evaporation, thereby reducing ocular signs and symptoms. The management of MGD includes home care options (eyelid hygiene, warming eye masks, ocular lubricants) and office-based treatments (manual expression, microblepharoexfoliation, thermal pulsation, intense pulsed light, intraductal probing).Topical ophthalmic prescription medications attempt to alter various factors that may contribute to DED (e.g., inflammation, bacterial growth, inadequate tear production). In this review, clinical evidence regarding available treatments and emerging therapies from randomized studies in patients with DED associated with MGD is summarized. Although some treatment modalities have been evaluated specifically for DED patients with MGD, largescale randomized controlled trials are needed to confirm efficacy and safety in this patient population. Currently, there are no approved prescription pharmacologic treatments specifically indicated for DED associated with MGD, and those medications approved for the treatment of DED do not target the key driver of the disease (i.e., excessive evaporation). NOV03 (perfluorohexyloctane; under review with the US Food and Drug Administration) is the most advanced emerging therapy for DED associated with MGD and has demonstrated statistically significant improvements in both signs and symptoms in randomized controlled trials. Development of novel pharmacotherapies will improve therapeutic options and allow for a more individualized approach for patients with DED associated with MGD.

Early-Stage Development of an Anti-Evaporative Liposomal Formulation for the Potential Treatment of Dry Eyes

“…DED remains a considerable public health concern, which affects a large portion of the global population . There are currently no curing treatments on the market for DED and leading ophthalmologists have proclaimed that there is an immediate demand for new types of DED-treatments that successfully target the tear film instability and excessive tear evaporation defects caused by the disorder . In this work, we set out to develop a new treatment strategy that is capable of targeting the main defects caused by DED.…”

“…While aqueous ocular lubricants are the most widely used treatments, they are unable to successfully target the tear film instability and excessive tear evaporation defect (present in >80% of DED-cases). − Thus, they offer only a brief alleviation of symptoms even upon frequent application. Anti-inflammatory agents, on the other hand, are associated with several adverse effects (e.g., ocular hypertension and cataracts) in long-term use, which poses a challenge when the chronic nature of some instances of DED is considered. − Therefore, the expert ophthalmologists have called for the immediate development of improved DED treatments capable of successfully targeting the tear film instability and excessive tear evaporation defects associated with the disease . Within the scientific community, there is a growing consensus that strategies focusing on the tear film lipid layer (TFLL) hold significant potential for improving the treatment outcomes.…”

“…15−17 Therefore, the expert ophthalmologists have called for the immediate development of improved DED treatments capable of successfully targeting the tear film instability and excessive tear evaporation defects associated with the disease. 18 Within the scientific community, there is a growing consensus that strategies focusing on the tear film lipid layer (TFLL) hold significant potential for improving the treatment outcomes. This is because the TFLL in healthy eyes is responsible for the upkeep of tear film stability and an optimal tear evaporation rate, 19 features that are compromised in dry eye patients because of structural/functional defects.…”

Potential applications of artificial intelligence in image analysis in cornea diseases: a review

“…It was found that blink videos with 30 FPS have higher accuracy in detecting incomplete blinking which was a sensitive indicator of DED [ 59 ]. Another important predictive factor of DED is meibomian gland dysfunction (MGD) which results in the disruption of the tear film lipid layer and increases the tear film evaporation rate [ 60 ]. A mask region based convolutional neural network (RCNN) algorithm has been explored in achieving automatic identification of MGD by applying it on analyses of 1878 non-invasive infrared meibography images [ 61 ].…”

Human Tear Protein Analysis Using a Quantitative Microfluidic System: A Pilot Study

“…Tear proteins can be classified according to their abundance. 3 The bulk of the tear protein concentration is made up of a few high abundance lacrimal proteins (mg/mL to mg/mL): lysozyme, lipocalin, lactoferrin, secretory immunoglobulin A (IgA), plasma-derived albumin, and lipophilin. 4,5 Proteins secreted by the ocular tissue or cell signaling molecules tend to be of moderate abundance (mg/mL to ng/mL) and cytokines and growth factors in low abundance (ng/mL to pg/ mL).…”