Examining treatment strategies for xanthelasma palpebrarum: a comprehensive literature review of contemporary modalities.

Xanthelasma palpebrarum (XP) is the predominant form of cutaneous xanthoma, as it accounts for greater than 95% of cases. It is characterized by the presence of foam cell clusters containing a large amount of low-density lipoprotein (LDL), which are located in the connective tissue of skin, tendons, and fascia. XP lesions commonly present as distinctive yellow-orange macules, papules, or nodules, and are primarily on the upper eyelids as well as the inner canthus. Women are affected twice as often as men, with lesions typically emerging between the ages of 35 and 55. The pathophysiology of XP involves abnormal lipid metabolism and is often associated with hyperlipidemic states like Type II and IV hyperlipidemia, hypothyroidism, weight gain, and fatty diet. Despite the availability of various treatment methods, current XP management lacks standardization, particularly due to limited comparative research. To address this gap, we conducted an extensive literature review of 45 studies published between 2012 to 2023, which provides an updated overview of current XP treatment modalities. This comprehensive analysis will inform researchers and clinicians on the evolving landscape of XP management.

Isolation and Culture of Human Meibomian Gland Ductal Cells.

Purpose: Hyperkeratinization of meibomian gland (MG) ducts is currently recognized as the primary pathologic mechanism of meibomian gland dysfunction (MGD). This research figured out a method to isolate the MG ducts and established a novel system to culture the human meibomian gland ductal cells (HMGDCs) for investigating the process of MGD. Methods: The MG ducts were obtained from the eyelids of recently deceased donors and subjected to enzymatic digestion. The acini were then removed to isolate independent ducts. These MG ducts were subsequently cultivated on Matrigel-coated wells and covered with a glass plate to obtain HMGDCs. The HMGDCs were further cultivated until passage 2, and when they reached 60% confluence, they were treated with IL-1ß and rosiglitazone for a duration of 48 hours. Immunofluorescence staining and Western blot techniques were employed to identify ductal cells and analyze the effects of IL-1ß on HMGDCs in an in vitro setting. Results: Ophthalmic micro-forceps and insulin needles can be employed for the purpose of isolating ducts. Within this particular culture system, the rapid expansion of HMGDCs occurred in close proximity to the duct tissue. MG ducts specifically expressed keratin 6 (Krt6) and hardly synthesized lipids. Furthermore, the expression of Krt6 was significantly higher (P < 0.0001) in HMGDCs compared to human meibomian gland cells. Upon treatment with IL-1ß, HMGDCs exhibited an overexpression of keratin 1, which was effectively blocked by the administration of rosiglitazone. Conclusions: The present study successfully isolated human MG ducts and cultured HMGDCs, providing a valuable in vitro model for investigating the mechanism of MGD. Additionally, the potential therapeutic efficacy of rosiglitazone in treating hyperkeratinization of ducts in patients with MGD was identified.

Meibomian Gland Dysfunction Is Associated with Low Levels of Immunoglobulin Chains and Cystatin-SN.

Meibomian gland dysfunction (MGD) is a highly prevalent condition and the most common cause of evaporative dry eye disease. Studying the proteome of MGD can result in important advances in the management of the condition. Here, we collected tear film samples from treatment naïve patients with MGD (n = 10) and age-matched controls (n = 11) with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography-tandem mass spectrometry. The proteins were considered differentially expressed if p < 0.05. A total of 88 proteins were significantly regulated. The largest change was observed in cystatin-SN, which was downregulated in MGD and correlated negatively with tear meniscus height. The downregulation of cystatin-SN was confirmed with targeted mass spectrometry by single reaction monitoring (SRM). Eighteen immunoglobulin components involved in B cell activation, phagocytosis, and complement activation were downregulated in MGD including Ig alpha-1 chain C region, immunoglobulin J chain, immunoglobulin heavy variable 3-15, and Ig mu chain C region. The changes in cystatin-SN and immunoglobulin chains are likely to result from the inflammatory changes related to tear film evaporation, and future studies may assess their association with the meibum quality.

Transitory alkali exposure on meibomian gland orifices induces meibomian gland dysfunction.

PURPOSE: To determine pathological changes of meibomian glands (MGs) after transient exposure of the rat eyelid margin to alkali solution. METHODS: Filter paper infiltrated with 1 N sodium hydroxide solution was applied to the eyelid margin of Sprague-Dawley rats for 30 s under general anesthesia, without touching the conjunctiva, after which the ocular surface and eyelid margin were examined by slit-lamp microscopy. In vivo confocal microscopy and stereomicroscopy were subsequently applied to observe MG morphology on day 5, day 10 and day 30 post alkali injury. Eyelid cross-sections were processed for H&E staining, Oil red O staining and immunofluorescent staining. RESULTS: After alkali injury, there was marked plugging of MG orifices, telangiectasia and hypertrophy of the eyelid margin, while corneal epithelium was intact at post-injury days 5 and 10. However, 30 days after alkali injury, mild corneal epithelial damage was observed. Degeneration of MG acini was observed at days 5 and became aggravated at days 10 and 30, along with MG duct dilation and acini loss. Oil red O staining showed lipid accumulation in the dilated duct. Inflammatory cell infiltration and the presence of apoptotic cells was seen in the MG loci 5 days post injury, but diminished at days 10 and 30. Cytokeratin 10 expression was increased in dilated duct, while cytokeratin 14, PPAR-γ, Ki67 and LRIG1 expression were decreased in the acini of injured loci. CONCLUSIONS: Transitory alkali exposure of the rat eyelid margin obstructs the MG orifice and induces pathological changes of MG dysfunction.

Meibomian gland development: Where, when and how?

The Meibomian gland (MG) is an indispensable adnexal structure of eye that produces meibum, an important defensive component for maintaining ocular homeostasis. Normal development and maintenance of the MGs is required for ocular health since atrophic MGs and disturbances in composition and/or secretion of meibum result in major ocular pathologies, collectively termed as Meibomian gland dysfunction (MGD). Currently available therapies for MGD merely provide symptomatic relief and do not treat the underlying deficiency of the MGs. Hence, a thorough understanding of the timeline of MG development, maturation and aging is required for regenerative purposes along with signaling molecules & pathways controlling proper differentiation of MG lineage in mammalian eye. Understanding the factors that contribute to the development of MGs, developmental abnormalities of MGs, and changes in the quality & quantity of meibum with developing phases of MGs are essential for developing potential treatments for MGD. In this review, we compiled a timeline of events and the factors involved in the structural and functional development of MGs and the associated developmental defects of MGs during development, maturation and aging.

The correlation between Demodex infestation and meibomian gland dysfunction at different ages.

BACKGROUND: This study aimed to explore the associations between Demodex infestation and the ocular surface characteristics of meibomian gland dysfunction (MGD) in different age groups, to further understand the effect of Demodex on MGD. METHODS: A total of 202 consecutive MGD patients aged 18 to 70 years were randomly recruited. All patients were divided into two groups based on their age: young patients (18-40 years) and elderly patients (41-70 years). The main observations were the different relationship between Demodex infestation and ocular surface and meibomian gland (MG) parameters in two age groups. We also compared ocular surface and MG parameters between the young and the elderly groups. Demodex infestation was diagnosed based on expert consensus in China. RESULTS: Our results indicated significant differences among young Demodex-positive, suspicious-positive, and negative patients in MG dropout (P = 0.000), plugging of MG orifices (P = 0.000), lid margin abnormality (P = 0.000), and meibum quality (P = 0.000). In elderly patients, there were significant differences among the Demodex-positive, suspicious-positive, and negative groups in terms of ocular surface disease index (OSDI) (P = 0.037), fluorescein tear film break-up time (FBUT) (P = 0.002), corneal fluorescein staining (CFS) (P = 0.036), MG dropout (P = 0.000), plugging of MG orifices (P = 0.008), lid margin abnormality (P = 0.000), and MG expression (P = 0.037). The mean number of mites in elderly Demodex-positive patients (10.64 ± 7.50) was greater than that of in young patients (7.60 ± 4.71) (P = 0.014). MG dropout (P = 0.000), plugging of MG orifices (P = 0.006), lid margin abnormality (P = 0.000), MG expression(P = 0.001), and meibum quality (P = 0.032) were more severe in elderly Demodex-positive patients. Additionally, FBUT (P = 0.005) was lower and tear film lipid layer thickness (LLT) (P = 0.001) was higher in the elderly. CONCLUSION: The effect of Demodex infestation on the ocular surface and MG parameters of MGD was different in patients of different ages. It is necessary to pay more attention to the diagnosis and treatment of Demodex infestation in MGD.

In-office thermal systems for the treatment of dry eye disease.

Dry eye disease affects millions of people worldwide, causing pain, vision disturbance, and reduced productivity. Meibomian gland dysfunction, a major cause of dry eye, is characterized by chronic glandular inflammation, thickening of the meibum, obstruction of terminal ducts, and glandular atrophy. Treatment of meibomian gland dysfunction can utilize heat and pressure applied to the meibomian glands, increasing meibum expression. With self-treatments, however, not all patients achieve lasting improvement, and compliance is often low. In-office thermal systems offer a second line of treatment and could be a much-needed addition for patients who do not respond to conventional treatment. We critically evaluated the efficacy and safety of LipiFlow, iLux, and TearCare based on existing literature. While the studies found a single in-office thermal treatment to be safe and effective in improving short-term signs and symptoms in patients with dry eye, long-term efficacy needs to be further evaluated. Thus, well-controlled, long-term efficacy studies are warranted to draw clear conclusions. The treatment seemed to provide rapid relief of symptoms that may last up to 1 year, but at a considerably higher cost than the at-home treatments. The choice of treatment depends on cost, compliance with at-home treatment, and personal preference.

Ocular surface alterations and changes of meibomian glands with meibography in type 1 diabetic children.

PURPOSE: To observe the changes of the ocular surface and meibomian glands by non-contact meibography in patients with type 1 diabetic children. METHODS: A total of forty-three patients with type 1 diabetic children and 43 age-matched healthy subjects were included in the study. The ocular surface disease index (OSDI) questionnaire, invasive tear film break-up time (TF-BUT), fluorescein staining of the ocular surface and Schirmer II test were performed for all participants. Ocular surface and lid margins were evaluated by slit lamp. Non-contact meibography was performed with the Phoenix-Meibography module in Sirius corneal topographic device. RESULTS: Both groups consisted of 25 (58.1%) female and 18 (41.9%) male children and the mean age was 14.4 ± 2.5 years. In the T1DM group, the mean disease duration was 6.8 ± 3.1 years. The mean TF-BUT (p = 0.002) and Schirmer II test (p = 0.007) measurements were lower in the diabetic group than those of in controls. Total eyelid score (p = 0.027) and meibomian gland (MG) secretion score (p = 0.007) were significantly high in diabetic children. MG area loss was also significantly high in both lower and upper eyelid (p < 0.001). In morphological analyses of meibomian glands thinning, shortening and presence of ghost areas (p = 0.05, p = 0.027 and p = 0.000, respectively) were more common in the diabetic group. There was no correlation between both lower and upper eyelid meiboscores and disease duration (p = 0.51 and p = 0.61), BMI (p = 0.08 and p = 0.51), serum HbA1c level (p = 0.06 and p = 0.49) and IGF-1 SDS (p = 0.38 and p = 0.68). CONCLUSION: The study revealed that the MG loss area increases and morphological alterations of meibomian glands occur in type 1 diabetic children. Disease duration and metabolic control of diabetes do not affect meibography measurements. CLINICAL TRIALS REGISTRATION: The study was organized in accordance with the ethical standards settled by the Ethics Committee of Faculty of Medicine, Afyonkarahisar Health Sciences University. TRIAL REGISTRATION NUMBER: 2011-KAEK-2, 2021/106. TRIAL REGISTRATION DATE: 02.05.2021.

The Ocular Surface Characteristics in Prostate Cancer Patients Treated with Androgen Deprivation Therapy.

BACKGROUND: To investigate the association of long-term androgen deprivation therapy (ADT) with ocular surface characteristics in prostate cancer patients. METHODS: A total of 30 male prostate cancer patients who received ADT were selected. All candidates were scored using the Ocular Surface Disease Index (OSDI) and subsequently divided into two groups containing 9 symptomatic patients (scores >12) and 21 asymptomatic patients (scores ≤ 12). Another 20 healthy age-matched males were selected as the control group. Each candidate was assessed with respect to eyelid margin abnormality, tear film break-up time (NI-BUT), tear meniscus height (TMH), meiboscore, meibum expressibility, and demodex infection. RESULTS: The NI-BUT in the ADT group was significantly shorter than that in the control group. The scores for OSDI, eyelid margin abnormality, meibum expressibility, and meiboscores were significantly higher in the ADT group (P < 0.05). Moreover, the NI-BUT in the symptomatic ADT group was significantly shorter than that in the asymptomatic ADT group (P < 0.05). The meiboscores and meibum expressibility score in the symptomatic ADT group were significantly higher than those in the asymptomatic ADT group (P < 0.05). The presence of demodex in the symptomatic ADT group was also higher than that in the asymptomatic ADT group (P < 0.05).The length of time that patients had been taking ADT was positively correlated with meiboscores and negatively correlated with NI-BUT. CONCLUSION: Androgen levels were associated with significant changes in relative meibomian gland function. Subjective symptoms, such as dryness and foreign body sensation, were more obvious in prostate cancer patients receiving ADT, which may be caused by MGD and demodex infection. It's recommended that more attention be paid to the ocular surface in prostate cancer patients taking ADT by performing examination of NI-BUT and meibomian gland morphology and function with a view to providing more comprehensive prevention and treatment protocols.

A spectroscopic approach to measuring meibum lipid composition and conformation in donors with SjÓ§gren's syndrome.

Patients with SjÓ§gren's syndrome (SS) have dry eye associated with meibomian gland dysfunction (MGD). The meibum from donors with dry eye due to MGD but without SS (MMGD) presents with lower levels of cholesteryl ester, less straight chains, and more ordered hydrocarbon chains compared with meibum from donors without MGD (Mn). The aim of the current study was to compare the composition and hydrocarbon chain conformation of meibum from donors with Sjögren's syndrome (Mss) to Mn and MMGD. Meibum was expressed from patients with SS using an ILUX instrument (Alcon Inc., Fort Worth TX). All of the nine meibum donors with SS were female. Meibum composition was characterized using 1H-NMR and meibum hydrocarbon chain conformation was measured using fourier transform infrared spectroscopy. Meibum from every donor with SS measured contained a significantly (P < 0.01) higher cholesteryl ester/wax ester ratio and more straight chains compared with donors without SS or dry eye. None of the nine phase transitional parameters were significantly different, P > 0.05, for Mss compared with Mn. Nor was the CH3/CH2 band height ratio used to estimate the number of hydrocarbon CH3 and CH2 moieties different, P = 0.22, for Mss compared with Mn. In conclusion, the compositional differences between Mss compared with Mn did not result in differences in any of the nine meibum lipid phase transitional parameters measured. The compositional differences observed between Mss and Mn could be markers for or contribute to SS as the differences could lead to tear film lipid packing differences other than conformational differences.

Lipidomic analysis of meibomian glands from type-1 diabetes mouse model and preliminary studies of potential mechanism.

Diabetes is a significant risk factor for meibomian gland dysfunction (MGD), but its mechanism is poorly understood. The main function of the meibomian glands (MGs) is to synthesize, store, and secrete lipids. In this study, we found that the amount of lipids in the meibomian acini in STZ-induced type 1 diabetic mice decreased, and the lipid droplets became larger and irregular. In all, 31 lipid subclasses were identified in the mouse MGs, which contained 1378 lipid species in total through lipidomics analysis based on LC-MS/MS. Diabetes caused a significant increase in the content of ceramides (Cer) in the MGs but a significant decrease in the ration of sphingomyelin to ceramides (SM/Cer). The quantity of meibocytes in diabetic mice was dramatically decreased, and the proliferation activity was alleviated, which may be associated with cell cycle arrest caused by diabetes-induced abnormal Cer metabolism in MGs. We found an increase in macrophage and neutrophils infiltration in the diabetic MGs, which may be related to the significant reduction of AcCa in diabetic MGs. Taken together, the results of the present study demonstrated that diabetes induced disruption of lipid homeostasis in MGs, which may mediate the decreased cell proliferation and increased inflammation caused by diabetes in MGs.

Prostaglandin F2α agonists induced enhancement in collagen1 expression is involved in the pathogenesis of the deepening of upper eyelid sulcus.

Previous our study reported that three-dimension (3D) cultures of human orbital fibroblasts (HOFs) replicated the etiology of deepening of the upper eyelid sulcus (DUES) caused by prostaglandin F2α analogues (PGF2α-ags). To examine this further, the effects of PGF2α-ags on HOFs were characterized by (1) lipid staining (2D; two-dimension, 3D), (2) comparison of the 3D organoid sizes of preadipocytes (DIF-) or adipocytes (DIF+) that had been treated with various concentrations of several PGF2α-ags, (3) physical stiffness (3D), and (4) the mRNA expression of adipogenic related genes, extracellular matrix (ECM), tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) (3D). PGF2α-ags caused a dramatic down-sizing of the 3D DIF+ organoids and this reduction was concentration dependent. The effects caused by PGF2α-ags were also observed in 3D preadipocytes. Micro-squeezer analysis clearly indicated that PGF2α-ags induced an increase in their physical solidity. The size of each organoid under several conditions was inversely correlated with the mRNA expression profile of collagen1 (COL1), TIMP2, and MMP2 and 9. These findings indicate that PGF2α-ags affect the expression of COL1, TIMP2, and MMP2 and 9 which, in turn, modulate the 3D ECM network within the organoids, thus resulting in their downsizing.

Comprehensive profiling of Asian and Caucasian meibomian gland secretions reveals similar lipidomic signatures regardless of ethnicity.

Meibum-a lipid secretion that is produced by Meibomian glands (MG) in a process termed meibogenesis-plays a critical role in ocular surface physiology. Abnormalities in the chemical composition of meibum were linked to widespread ocular pathologies-dry eye syndrome (DES) and MG dysfunction (MGD). Importantly, in epidemiologic studies the Asian population was shown to be prone to these pathologies more than the Caucasian one, which was tied to differences in their meibomian lipids. However, biochemical data to support these observations and conclusions are limited. To determine if non-DES/non-MGD Asian meibum was significantly different from that of Caucasians, individual samples of meibum collected from ethnic Asian population living in Japan were compared with those of Caucasians living in the USA. These experiments revealed that composition of major lipid classes, such as wax esters (WE), cholesteryl esters (CE), triacylglycerols, (O)-acylated ω-hydroxy fatty acids (OAHFA), cholesteryl sulfate, cholesteryl esters of OAHFA, and diacylated α,ω-dihydroxy fatty alcohols remained invariable in both races, barring a minor (< 10%; p < 0.01) increase in the Asian CE/WE ratio. Considering the natural variability range for most meibomian lipids (app. ± 15% of the Mean), these differences in meibogenesis were deemed to be minimal and unlikely to have a measurable physiological impact.

Effects of collagen crosslinking on porcine and human tarsal plate.

BACKGROUND: Floppy eyelid syndrome is a disorder in which the tarsal plate is easily distensible and is currently treated with conservative or surgical measures. Human tarsal plate contains type I collagen, which is crosslinked in corneal tissue as a treatment for keratoconus. We hypothesized that collagen crosslinking would similarly stiffen tarsal plate tissue and investigated this in porcine and human tarsal plate specimens. METHODS: Riboflavin-sensitized porcine and human tarsus samples were irradiated with ultraviolet-A light. Porcine experiments were analyzed with gross photographs, anterior segment optical computed tomography (AS-OCT) imaging, and tensile testing. A prospective study of human tarsus was performed on samples from patients undergoing wedge resection for floppy eyelid syndrome and was analyzed with AS-OCT and tensile testing. RESULTS: 73 porcine adnexa and 9 patients (16 eyelids) who underwent wedge excision were included in the study. Grossly, greater stiffness was observed in crosslinked porcine tissue. AS-OCT imaging in porcine tissue showed a distinct hyperreflective band in crosslinked specimens whose area and intensity increased with longer treatment time (P = 0.003); this band was also visible in crosslinked human specimens. Tensile testing was performed, but results were not statistically significant. CONCLUSIONS: AS-OCT imaging, which has not been previously described for tarsal plate, showed a characteristic change in crosslinked porcine and human specimens. Tissue stiffness was increased grossly, but changes in tensile properties were not statistically significant. Further study is warranted to determine relevance as a potential treatment for floppy eyelid syndrome.

Endometriosis of the Eyelid, an Extraordinary Extra-abdominal Location Highlighting the Spectrum of Disease.

Cutaneous endometriosis is an uncommon dermatologic disorder predominantly seen in young women. Most commonly, it presents within a region of a previous surgical scar, often in relation to a gynecologic procedure on the abdomen or in close proximity to the umbilicus. The typical clinical presentation is that of papules or nodules with monthly cyclical pain and size variation. Histologically, the lesions are composed of endometrial stroma and glands. The pathophysiology is not well understood but is believed to be due to metastasis or seeding of endometrial cells. When this uncommon disorder occurs outside of the most typical clinical setting, it may cause some diagnostic difficulty. In this report, we present the first known case of cutaneous endometriosis on the eyelid.

Distribution and Characteristics of Meibomian Gland Dysfunction Subtypes: A Multicenter Study in South Korea.

PURPOSE: We sought to evaluate the distribution and characteristics of meibomian gland dysfunction (MGD) and the treatment patterns for symptomatic MGD patients in South Korea. METHODS: One hundred ninety-six right eyes of 196 MGD patients were enrolled. For each patient, meibum expressibility in the central eight glands in both the upper and lower eyelids was examined. Each upper and lower eyelid was separately classified into one of the following three subtypes: nonobvious obstructive (low-delivery without lid margin abnormality), obvious obstructive (low-delivery with lid margin abnormality), and hypersecretory (high-delivery with lid margin abnormality). All treatment plans were also recorded. RESULTS: The mean number of expressible glands of the central eight glands in the upper eyelids (3.9 ± 2.6) was significantly higher than that in the lower eyelids (2.2 ± 2.4, p < 0.001). Obvious obstructive MGD was the most common subtype, followed by the hypersecretory and nonobvious obstructive subtypes in both the upper and lower eyelids. Of the 196 subjects, 38 (19.4%) had upper and lower eyelids that were assigned to different categories. Eyelid hygiene was the most prescribed treatment (74.5%), followed by lubricant eye drop usage (71.5%). Physicians tended to determine treatment plans based on the subtype of the upper eyelid rather than that of the lower eyelid. CONCLUSIONS: The majority of subjects were classified as having the obvious obstructive subtype of MGD, and 19.4% had upper and lower eyelids that were different subtypes. Eyelid hygiene was the most prescribed treatment for MGD patients, and treatment patterns were mostly determined based on the subtype of the upper eyelids.

Efficacy of azithromycin 1.5% eyedrops vs oral doxycycline in meibomian gland dysfunction: a randomized trial.

PURPOSE: To determine the efficacy of azithromycin 1.5% eyedrops compared with oral doxycycline in patients with moderate to severe meibomian gland dysfunction (MGD). METHODS: This prospective randomized trial included 169 participants with newly diagnosed moderate to severe MGD. Participants were randomly assigned to treatment with azithromycin 1.5% eyedrops (n = 85) twice daily for 2 days then once daily until 4 weeks or oral doxycycline (n = 84) 100 mg twice daily for 4 weeks. Signs and symptoms of MGD were evaluated at baseline and 4 weeks later. The percentages of participants with improvement in meibum quality were assessed as a primary outcome. Secondary outcomes were MGD-related symptoms, meibum expressibility, Oxford ocular surface staining score, tear film break up time (TBUT), and drug side effects. RESULTS: Although there were significant improvements in all outcomes in both groups, there was no between-group differences in the percentages of participants with improved meibum quality (P = 0.80), MGD-related symptoms (P > 0.05), meibum expressibility (P = 0.92), Oxford ocular surface staining score (P = 0.59), and TBUT (P = 0.99). Five (5.88%) participants in azithromycin group and four (4.76%) participants in doxycycline group discontinued medications due to drug side effects (P = 0.75). CONCLUSIONS: Both azithromycin 1.5% eyedrops and oral doxycycline significantly improved signs and symptoms in patients with moderate to severe MGD. Both azithromycin 1.5% eyedrops and oral doxycycline showed no difference in term of improved signs and symptoms of MGD as well as drug side effects that lead to discontinuation of medication.

Advances in dry eye disease treatment.

PURPOSE OF REVIEW: The prevalence and burden of dry eye disease continues to grow at a rapid pace, creating an increased need for new therapies. In a sector once limited to only a handful of treatments, clinicians now have multiple options available for patients who fail traditional therapies. This review summarizes the various treatment options available to clinicians treating complex dry eye disease patients. RECENT FINDINGS: As we better understand the multifactorial mechanisms leading to dry eye disease, treatments increasingly focus on the amelioration of the underlying deficiencies and inflammation, rather than on transient symptomatic relief alone. Most topical medications seek to replace deficient growth factors and/or decrease inflammation on the ocular surface. The majority of new devices and procedures seek to treat meibomian gland dysfunction, with one new device stimulating tear production through utilizing the nasolacrimal reflex pathway. SUMMARY: Clinicians have more options at their disposal in the treatment of dry eye disease than ever before, including topical medications and devices.

The quantitative measuring method of meibomian gland vagueness and diagnostic efficacy of meibomian gland index combination.

PURPOSE: To propose and to evaluate a quantitative measuring method of meibomian gland (MG) vagueness. METHODS: A total of 47 patients (32 female and 15 male, 39.21 ± 11.07 years) with meibomian gland dysfunction (MGD) were recruited to the MGD group, and 47 healthy volunteers were recruited to the control group matched in age and gender. The clinical examinations included ocular surface evaluation, MG function indexes and MG morphological indexes (including MG vagueness value). Reliability and efficacy of MG vagueness value, correlation between vagueness value and relevant variables, and diagnostic efficacy of combining vagueness value with efficacious indexes were all evaluated. RESULTS: The MG vagueness value of the MGD group (19.78 ± 13.17) was significantly lower than that of the control group (31.90 ± 13.15). The vagueness value possessed good between-reader reliability (intraclass correlation coefficient = 0.928 > 0.9), and was correlated with age (r = -0.356), most clinical indexes and the acinar shortest diameter (r = -0.278). The area under the curve (AUC) in the receiver operating characteristic (ROC) curve of vagueness value was 0.766 [95% confidence interval (CI): 0.668-0.864] with sufficient diagnostic efficacy, and the cutoff value was <21. The AUC improved to 0.956 (95% CI: 0.938-0.999), after efficacious indexes (vagueness value, meiboscore and tear breakup time) were combined. CONCLUSION: Meibomian gland (MG) vagueness is quantifiable. The MG vagueness value proposed in this study has good reliability, a close relationship with MGD clinical features and sufficient diagnostic efficacy. Combining this new index with other indexes commonly used offers an exciting prospect in MGD diagnosis.