Evaluation of the effect of Muller muscle-conjunctival resection on meibomian glands by meibography

ABSTRACT Purpose: To evaluate the effect of upper eyelid ptosis repairwith Muller muscle-conjunctival resection on meibomian gland function and ocular surface parameters. Methods: Thirty-eight patients who underwent ptosis repair with Muller muscle-conjunctival resection were retrospectively reviewed. Meibomian gland loss, Ocular Surface Disease Index OXFORD score, meiboscore, and noninvasive keratograph break-up time were measured preoperatively and at 1st, 3rd, and 6th months postoperatively. Results: Noninvasive keratograph break-up time values decreased significantly at 1st and 3rd months postoperatively compared to the preoperative level, but were similar to the preoperative level at 6th months postoperatively (p<0.001 and p=0.628, respectively). Ocular surface disease index, OXFORD score, meibomian gland loss, and meiboscore values increased significantly in the 1st and 3rd postoperative months compared to the preoperative period, but these values decreased to preoperative levels in the 6th postoperative month (p<0.001 and p>0.05, respectively). Conclusion: There is a transient deterioration in meibography findings and OSDI score in the early postoperative period afterMuller muscle-conjunctival resection. Patients undergoing Muller muscle-conjunctival resection may require topical lubricants, especially in the first 3 postoperative months.

Effect of Heating and Massaging of Meibomian Glands on Their Imaging.

Background and Objectives: Infrared light is used to image the Meibomian glands through their thermal profile. This study aimed to investigate the effects of a combination of heating and an eyelid massage on Meibomian gland visibility and tear film parameters. Materials and Methods: Twenty-four participants (26 ± 6.9 years) were enrolled in this prospective study, which involved imaging the Meibomian glands of both the lower and upper eyelid and assessing the non-invasive breakup time (NIBUT), tear meniscus height (TMH), and blink rate (using the CA-800, Topcon) at baseline after five minutes of eyelid warming followed by a five-minute eyelid massage. The second session, which was randomised in sequence, repeated the same measurements but without the inclusion of any eyelid warming or massage as the control condition. Results: While there was no change in lower lid Meibomian gland appearance as a result of eyelid heating, eyelid massage, or multiple lid eversion (median 2.0, range 0.0 to 4.0; p = 0.782), there was a change in upper lid appearance 5 min after heating and lid massage (p = 0.025), but again, multiple lid eversion had no effect (p > 0.05). The NIBUT decreased on second lid eversion (p = 0.049), although this was not evident on the third lid eversion (p = 0.090). The effect on NIBUT was also apparent with heating (p = 0.034 immediately after) but was sustained with 5 min of eyelid massage (p = 0.031). The TMH increased with heating (p < 0.001), and this effect was sustained with 5 min of eyelid massage (p = 0.011), but there was no lid eversion effect (p > 0.05). The blink rate was unaffected by heating, eyelid massage, or multiple eversions of the eyelids (median 24 blinks/min, range 8 to 59 blinks/min; p = 0.61). Conclusions: Eyelid warming can increase the visibility of the Meibomian glands, although this effect was only observed with upper lid imaging and the effect dissipated after 5 min of eyelid massage. Warming and massage also disrupt the tear film, as does multiple lid eversion, emphasising the need to use the least invasive tear film assessment techniques first.

Meibomian gland dropout of upper eyelids as a novel biomarker for early diagnosis of primary Sjögren's syndrome: a pilot study.

Background: Early diagnosis of primary Sjögren's syndrome (pSS) remains difficult due to its insidious onset. Objectives: To identify whether meibomian gland dropout (MGD) is a sensitive and noninvasive predictor of pSS by studying its association with histopathology in labial salivary gland biopsy in patients with clinically suspected pSS. Design: Prospective, randomized, multicenter, comparative effectiveness study. Methods: The study was conducted from July 2022 to July 2023. In all, 56 eligible participants with clinically suspected pSS were recruited from three combined ophthalmology medicine/rheumatology SS clinics. All participants with suspected pSS were evaluated and diagnosed by ophthalmology and rheumatology consultants and underwent infrared imaging of the meibomian glands using Keratograph 5M and histopathological evaluation of labial salivary gland biopsies. The length, width, and tortuosity of the meibomian glands were measured; the dropout rate in the nasal, temporal, and total eyelids was analyzed; and the dropout score was calculated using meibography grading scales. Results: Among the 56 participants, 34 were identified with pSS, and 22 were diagnosed with non-SS dry eye (NSSDE) and served as the control group. We recorded significant differences in the temporal and total MGD rates of the upper eyelids between the pSS and NSSDE groups (all p < 0.01). Improved prediction accuracy was achieved with the temporal and total MGD rates in the upper eyelids, with area under the curve values of 0.94 and 0.91, and optimal cutoff points of 0.78 and 0.75, respectively. Conclusion: MGD in the upper eyelids, especially in the temporal portion, is strongly associated with the histopathological outcome of labial salivary gland biopsy in pSS and is proposed as a highly predictive and noninvasive biomarker for the early diagnosis of pSS. Trial registration: ClinicalTrials.gov identifier: ChiCTR2000038911.

Evaluating the role of Demodex infestation and meibomian gland dysfunction in recurrent corneal erosion syndrome.

This investigation aims to observe the effects of demodex infection and meibomian gland function in recurrent corneal erosion syndrome (RCES), as well as the efficacy of intense pulsed light (IPL) in treating RCES. The study enrolled thirty patients diagnosed with RCES (30 eyes) alongside a control group of thirty-one individuals (31 eyes). Both cohorts underwent a series of diagnostic evaluations, including eyelash sampling, Demodex mite enumeration, infrared imaging of the meibomian glands, and blepharolipin scoring. The RCES subjects were further categorized into two subgroups upon stabilization for comparative analysis of treatment outcomes: the RCES-A subgroup received IPL therapy (16 patients), and the RCES-B subgroup was administered medication treatment (14 patients). Post-treatment, all participants were re-evaluated using the initial diagnostic procedures to monitor for recurrence. Preliminary findings indicated significant differences between the RCES and control groups in terms of meibomian gland scores (4 [3.0, 4.0] vs. 2 [1.0, 3.0]), blepharolipin scores (15.5 [11.0, 16.8] vs. 8.0 [5.5, 10.0]), and lid margin scores (3.0 [2.8, 3.0] vs. 2.0 [1.0, 3.0]), with P < 0.01 for all comparisons. Additionally, the Demodex count was significantly higher in the RCES group (8.0 [4.0,9.0]) compared to the control (0 [0, 2]) (Z = - 4.13, P = 0.00), with a Demodex positivity rate of 83.3% in the RCES group versus 38.7% in the control group (χ2 = 7.60, P < 0.01). Post-treatment, the RCES-A subgroup exhibited significant improvements in meibomian gland loss scores, blepharolipin scores, lid margin abnormality scores, and a reduction in Demodex counts (P < 0.01), with a post-treatment Demodex positivity rate of 56.3% (P = 0.11). During the follow-up, the RCES-A subgroup experienced a lower relapse rate compared to the RCES-B subgroup (1 vs. 6 patients). The findings suggest a correlation between meibomian gland dysfunction and Demodex infestation with the incidence of RCES. The application of IPL therapy in combination with meibomian gland massage demonstrates significant potential in enhancing meibomian gland functionality, reducing Demodex counts, and effectively mitigating the recurrence of RCES. Clinical trial registration: https://www.chictr.org.cn/ ChiCTR2000039494 (30/10/2020).

Topical anti-glaucoma medications effects on meibomian glands: Systematic review and meta-analysis.

Meibomian gland (MG) dysfunction and glaucoma are very prevalent ocular conditions that significantly impact patients' quality of life. A growing number of clinical and experimental studies have reported an association between the use of topical eye drops to reduce intraocular pressure and the development or exacerbation of MG dysfunction. Studies investigating the impact of glaucoma eyedrops on MG diagnostic parameters have shown variable results, particularly regarding the morphology and function of MG and tear film instability. Herein, we corroborated the findings of greater changes in morphological and functional variables related to MG in patients treated with antiglaucoma eye drops through a systematic review and meta-analysis.

Evaluation of Meibomian Gland Structure and Function in Patients with Vernal Keratoconjunctivitis Using Non Contact Meibography and Lipid Layer Interferometry.

PURPOSE: This study evaluated the structural and functional impact of vernal keratoconjunctivitis (VKC) on meibomian glands (MGs) using a combination of noncontact meibography and lipid layer interferometry. METHODS: In this observational study 50 patients with moderate persistent or severe VKC and 50 age-matched controls underwent MG imaging and lipid layer thickness (LLT) measurements with Lipiview II. Image J software was used to assess MG loss (meibograde) in both lids. All patients underwent dry eye evaluation comprising tear break-up time (TBUT), ocular surface staining (OSS), Schirmer I scoring, and meiboscoring (expressibility and quality of meibum secreted). RESULTS: Meibograde, OSS score, and meiboscore was higher in cases (2.68 ± 0.96, 0.580 ± 1.07, and 0.56 ± 0.95 respectively) than controls (1.80 ± 0.67, 0.00 ± 0.00, 0.22 ± 0.47 respectively) (p < 0.001, 0.001, 0.025 respectively). LLT and TBUT was lower in cases (54.58 ± 9.43 nm and 4.92 ± 3.09 sec respectively) than controls (70.14 ± 22.50 nm and 12.02 ± 2.73 sec respectively) (both p's = 0.001). Both groups had comparable Schirmer I scores. CONCLUSION: Children with VKC have significant MG dropouts, deterioration in meibum quality and a thinner and less stable tear film. VKC patients are thus prone to a vicious cycle of inflammation attributable both to the allergic component and to deterioration in MG structure and function. Co-management of MG dysfunction warrants as much attention as the allergic component itself.

Tear film assessment before and after phacoemulsification in patients with age-related cataracts.

BACKGROUND: The study aims to assess the tear film before and after phacoemulsification in patients with age-related cataracts. METHODS: A prospective observational study of 41 age-related cataract patients undergoing phacoemulsification procedure. Tear Film Break-Up Time (TBUT), Tear Film Meniscus Height (TMH), Meibomian glands (MG), and Lipid Layer Thickness (LLT) were assessed by a non-invasive Dry Eye Diagnostic System. All measurements were taken preoperatively, one week, one month, and three months postoperatively. The Marginal homogeneity and The Cochran Q tests were used in the statistical analysis. RESULTS: The value of Non-Invasive Break-Up Time (NITBUT) was statistically significantly lower at one week (7.15 ± 3.31), one month (7.61 ± 3.41), and three months (7.66 ± 3.36) postoperatively than preoperatively (10.71 ± 2.71), p < 0.001. The Non- Invasive Tear Meniscus Height (NITMH) was significantly lower at one week (0.18 ± 0.0), one month (0.20 ± 0.09), and three months (0.20 ± 0.09) postoperatively than preoperatively (0.30 ± 0.113) p < 0.001. By the first month, both (NITBUT) and (NITMH) improved significantly compared to the first post-operative week. There was no statistically significant difference between one month and three months. The (NITMH) improved to a healthy level of ≥ 0.2 mm by the first month through the third month. Both (NITBUT) and (NITMH) did not reach the baseline by the third month. The meibomian glands and the lipid layer thickness had the same preoperative grade distribution without changes. CONCLUSION: Phacoemulsification surgery can cause post-operative deterioration in the tear film, which starts within a week of the procedure, followed by gradual recovery over the next weeks and months. The phacoemulsification procedure mainly affects the tear break-up time and tear meniscus height. Both the lipid layer and meibomian glands are not affected.

Management of Glaucoma-Related Dry Eye Disease with Intense Pulsed Light: A Randomized Control Study.

Purpose: The objective of this study was to assess the effectiveness of intense pulsed light (IPL) therapy in individuals diagnosed with glaucoma and dry eye disease (DED). Methods: This randomized control study recruited 22 individuals diagnosed with glaucoma, ranging in age from 33 to 82 years. These participants were undergoing treatment with hypotensive eyedrops and had clinical indications and subjective complaints associated with dry eye. Each patient underwent three sessions of IPL therapy in one eye, while the contralateral eye served as the control eye (CT). The following parameters were assessed at three time points: baseline, week-2, and week-4. These parameters include non-invasive breakup time (NITBUT), tear meniscus height (TMH), conjunctivocorneal epithelial staining score (CS), tear film lipid layer (TFLL), meibomian gland expressibility score (MGEx), Schirmer I test, ocular bulbar redness score (OBRS), and ocular surface disease index (OSDI). Intraocular pressure (IOP), best-corrected visual acuity (BCVA), and corneal endothelial cell count (ECC) were assessed for safety. The clinical trial was registered on 25/12/2023 at ClinicalTrials.gov website (NCT06158984). Results: Comparing baseline and 4-week measurements revealed that the IPL group found significant improvements in NITBUT (IPL: 8.74±2.60 sec. vs CT: 5.76±1.75 sec. p<0.01), TMH (IPL: 0.23±0.05mm vs CT: 0.19±0.06mm, p=0.011), C.S. (IPL: 1.14±0.56 vs CT: 1.95±1.17, p=0.005), TFLL (IPL: 2.91±2.91 vs CT:3.36±0.58, p=0.047), MGEx score (IPL: 1.14±0.35 vs CT: 1.45±0.51, p=0.020) and OSDI scores (IPL: 31.77±15.59 vs 50.59±21.55, p=0.002) significantly improved. Conversely, other parameters showed no significant improvements (p>0.05). Conclusion: The progression of ocular surface disease in individuals using topical anti-glaucoma medication may worsen if the condition is not addressed. Nevertheless, IPL therapy has the potential to result in significant improvements in both objective and subjective measures of dry eye. Best-corrected visual acuity, endothelial cell count, and intraocular pressure were determined to be within the permitted limits. No adverse events were reported during the course of the study.

The results show that people who use topical medicines to treat glaucoma may get worse eye surface disease if they do not treat the problem. IPL treatment, on the other hand, can make a big difference in both objective and subjective dry eye tests. The vision, endothelial cell count, and the pressure inside the eye were all found to be within normal limits after the IPL treatment. Even though the people in our study had glaucoma and had been taking glaucoma medicine for it for a year and the fact that the symptoms last for a long time may also change the results. Also, DED caused by glaucoma medication is complicated, with a lot of different symptoms and signs, even in the same stage. Also, subjective complaints may not match up with clinical signs. The type, amount, and length of anti-glaucoma drugs may have affected the results.

Factors affecting meibomian gland area loss in symptomatic adults.

AIM: To characterize the distribution of meibomian gland (MG) area loss (MGL) and its relationship with demographic characteristics, mites, and symptoms. METHODS: This retrospective observational study included patients who visited the Dry Eye Clinic of Shenzhen Eye Hospital between June 2020 and August 2021. General patient characteristics, ocular symptoms, Demodex test results of the eyelid edges, and the results of a comprehensive ocular surface analysis were collected. MGL was analyzed using Image J software. RESULTS: This study enrolled 1204 outpatients aged 20-80 (40.70±13.44)y, including 357 males (29.65%) and 847 females (70.35%). The patients were classified into mild (n=155; 12.87%), moderate (n=795; 66.03%), severe (n=206; 17.11%), and extremely severe (n=48; 3.99%) MGL groups. MGL was significantly larger in female than in male (P=0.006). The degree of MGL also significantly differed in age (P<0.001) and the more numbers of mites with severity (P<0.001). Multivariate disordered multinomial logistic regression analysis identified that female sex, older age, secretory symptoms, and a large number of mites were risk factors for MGL (P<0.05). CONCLUSION: Patients with MGL are more likely to be older, female, more numbers of mites, and increased secretion.

Meibomian glands segmentation in infrared images with limited annotation.

AIM: To investigate a pioneering framework for the segmentation of meibomian glands (MGs), using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis. METHODS: Totally 203 infrared meibomian images from 138 patients with dry eye disease, accompanied by corresponding annotations, were gathered for the study. A rectified scribble-supervised gland segmentation (RSSGS) model, incorporating temporal ensemble prediction, uncertainty estimation, and a transformation equivariance constraint, was introduced to address constraints imposed by limited supervision information inherent in scribble annotations. The viability and efficacy of the proposed model were assessed based on accuracy, intersection over union (IoU), and dice coefficient. RESULTS: Using manual labels as the gold standard, RSSGS demonstrated outcomes with an accuracy of 93.54%, a dice coefficient of 78.02%, and an IoU of 64.18%. Notably, these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%, 2.06%, and 2.69%, respectively. Furthermore, despite achieving a substantial 80% reduction in annotation costs, it only lags behind fully annotated methods by 0.72%, 1.51%, and 2.04%. CONCLUSION: An innovative automatic segmentation model is developed for MGs in infrared eyelid images, using scribble annotation for training. This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs. It holds substantial utility for calculating clinical parameters, thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

Temporal variations in meibomian gland structure-A pilot study.

PURPOSE: To investigate whether there is a measurable change in meibomian gland morphological characteristics over the course of a day (12 h) and over a month. METHODS: The study enrolled 15 participants who attended a total of 11 study visits spanning a 5-week period. To assess diurnal changes in meibomian glands, seven visits were conducted on a single day, each 2 h apart. For monthly assessment, participants attended an additional visit at the same time of the day every week for three consecutive weeks. Meibography using the LipiView® II system was performed at each visit, and meibomian gland morphological parameters were calculated using custom semi-automated software. Specifically, six central glands were analysed for gland length ratio, gland width, gland area, gland intensity and gland tortuosity. RESULTS: The average meibomian gland morphological metrics did not exhibit significant changes during the course of a day or over a month. Nonetheless, certain individual gland metrics demonstrated notable variation over time, both diurnally and monthly. Specifically, meibomian gland length ratio, area, width and tortuosity exhibited significant changes both diurnally and monthly when assessed on a gland-by-gland basis. CONCLUSIONS: Meibomian glands demonstrated measurable structural change over short periods of time (hours and days). These results have implications for innovation in gland imaging and for developing precision monitoring of gland structure to assess meibomian gland health more accurately.

A CXCR3-Activating Peptide Increases Tear Break Up Time and Corrects Corneal haze in a Rabbit Model of Environmental Dry Eye.

Purpose: Environmentally-triggered dry eye disease (DED) or keratoconjunctivitis sicca (KCS), which constitutes the majority of DED cases, currently is palliatively treated with aqueous replacement solutions that do not target the dysfunction of the mucin and lipid components of tears. We tested whether a peptide that increased goblet cell numbers in a model of scleral chemical injury would also improve tear quality in environmental DED. Methods: Environmental DED was established by exposing New Zealand white rabbits (8 per group, female) to 20% humidity with rapid air replacement and b.i.d. atropine sulfate eyedrops for 3 weeks prior to test article administration; this continued for the subsequent 3 weeks of testing. Animals were dosed by (A) saline, (B) b.i.d. eyedrop of peptide in saline, (C) b.i.d. eyedrop of peptide in coacervate, or (D) weekly subconjunctival injection of peptide. In vitro, human conjunctival epithelial cells (HCjE) were exposed to TNFα in the presence or absence of peptide to determine inflammatory responsiveness. Results: The environmental DED was established with both Schirmer and TBUT being reduced at the start of test article; these levels were maintained as low through the testing period. All three treatment regimens increased TBUT approximately 3x to levels greater than prior to desiccation (P < 0.01), with little effect on Schirmer. Corneal haze was present in all eyes after induction, and completely reversed in 36 of 48 eyes across the treatments (P < 0.05). Co-treatment of HCjE with peptide reduced the production of TNFα in response to an inflammatory stimulus. Conclusions: The treatment of environmental DED/KCS with a peptide that activates CXCR3 improved tear quality and reversed corneal pathology by promoting tear stability and likely dampening the corneal inflammation, while not affecting aqueous volume of the tears.

Comparative Characterization of Human Meibomian Glands, Free Sebaceous Glands, and Hair-Associated Sebaceous Glands Based on Biomarkers, Analysis of Secretion Composition, and Gland Morphology.

Meibomian gland dysfunction (MGD) is one of the main causes of dry eye disease. To better understand the physiological functions of human meibomian glands (MGs), the present study compared MGs with free sebaceous glands (SGs) and hair-associated SGs of humans using morphological, immunohistochemical, and liquid chromatography-mass spectrometry (LCMS)-based lipidomic approaches. Eyelids with MGs, nostrils, lips, and external auditory canals with free SGs, and scalp with hair-associated SGs of body donors were probed with antibodies against cytokeratins (CK) 1, 8, 10, and 14, stem cell markers keratin 15 and N-cadherin, cell-cell contact markers desmoglein 1 (Dsg1), desmocollin 3 (Dsc3), desmoplakin (Dp), plakoglobin (Pg), and E-cadherin, and the tight junction protein claudin 5. In addition, Oil Red O staining (ORO) was performed in cryosections. Secretions of MGs as well as of SGs of nostrils, external auditory canals, and scalps were collected from healthy volunteers, analyzed by LCMS, and the data were processed using various multivariate statistical analysis approaches. Serial sections of MGs, free SGs, and hair-associated SGs were 3D reconstructed and compared. CK1 was expressed differently in hair-associated SGs than in MGs and other free SGs. The expression levels of CK8, CK10, and CK14 in MGs were different from those in hair-associated SGs and other free SGs. KRT15 was expressed differently in hair-associated SGs, whereas N-cadherin was expressed equally in all types of glands. The cell-cell contact markers Dsg1, Dp, Dsc3, Pg, and E-cadherin revealed no differences. ORO staining showed that lipids in MGs were more highly dispersed and had larger lipid droplets than lipids in other free SGs. Hair-associated SGs had a smaller number of lipid droplets. LCMS revealed that the lipid composition of meibum was distinctively different from that of the sebum of the nostrils, external auditory canals, and scalp. The 3D reconstructions of the different glands revealed different morphologies of the SGs compared with MGs which are by far the largest type of glands. In humans, MGs differ in their morphology and secretory composition and show major differences from free and hair-associated SGs. The composition of meibum differs significantly from that of sebum from free SGs and from hair-associated SGs. Therefore, the MG can be considered as a highly specialized type of holocrine gland that exhibits all the histological characteristics of SGs, but is significantly different from them in terms of morphology and lipid composition.

Quantitative evaluation of morphological and functional changes in meibomian glands and lipid layer thickness in patients with and without keratoconus.

PURPOSE: To quantitatively evaluate the morphological parameters of meibomian glands (MGs) and lipid layer thickness (LLT) in patients with keratoconus (KC). METHODS: In this prospective, cross-sectional study, 164 eyes of 164 keratoconus patients and 64 eyes of 64 age-matched control subjects were included. An advanced automatic MG analyzer was used to quantitatively measure the morphological and functional parameters of MGs. Morphological and functional parameters of MGs, LLT, and other ocular surface parameters were compared between the control and KC groups. RESULTS: The mean meibomian gland diameter, length, square, and gland area ratio (GA) were all significantly decreased in the KC group (all P < 0.05), while no significant difference was observed in the gland tortuosity index (TI) and gland signal index (SI) between the KC and control groups (all P > 0.05). There was no significant difference in the number of total and incomplete blinking among patients with different stages of keratoconus (all P > 0.05). The gland diameter, square, and TI were all negatively associated with KC severity (all P < 0.05), while no significant difference was observed among all stages of KC in gland length, GA, and SI (all P > 0.05). Moreover, the LLTs were positively correlated with the gland diameter, square, GA, and TI and negatively correlated with anterior corneal curvature or KC severity (all P < 0.05). CONCLUSIONS: Atrophic morphological changes in the meibomian glands were closely correlated with the severity of keratoconus. Gland diameter may be a sensitive functional morphology metric of meibomian glands in patients with keratoconus.

Absent meibomian glands and cone dystrophy in ADULT syndrome: identification by whole exome sequencing of pathogenic variants in two causal genes TP63 and CNGB3.

BACKGROUND: Ectrodactyly is a rare congenital limb malformation characterized by a deep median cleft of the hand and/or foot due to the absence of central rays. It could be isolated or depicts a part of diverse syndromic forms. Heterozygous pathogenic variants in the TP63 gene are responsible for at least four rare syndromic human disorders associated with ectrodactyly. Among them, ADULT (Acro-Dermato-Ungual-Lacrimal-Tooth) syndrome is characterized by ectodermal dysplasia, excessive freckling, nail dysplasia, and lacrimal duct obstruction, in addition to ectrodactyly and/or syndactyly. Ophthalmic findings are very common in TP63-related disorders, consisting mainly of lacrimal duct hypoplasia. Absent meibomian glands have also been well documented in EEC3 (Ectrodactyly Ectodermal dysplasia Cleft lip/palate) syndrome but not in ADULT syndrome. METHODS: We report a case of syndromic ectrodactyly consistent with ADULT syndrome, with an additional ophthalmic manifestation of agenesis of meibomian glands. The proband, as well as her elder sister, presented with congenital cone dystrophy.The molecular investigation was performed in the proband using Whole Exome Sequencing. Family segregation of the identified variants was confirmed by Sanger sequencing. RESULTS: Two clinically relevant variants were found in the proband: the novel de novo heterozygous missense c.931A > G (p.Ser311Gly) in the TP63 gene classified as pathogenic, and the homozygous nonsense pathogenic c.1810C > T (p.Arg604Ter) in the CNGB3 gene. The same homozygous CNGB3 variation was also found in the sister, explaining the cone dystrophy in both cases. CONCLUSIONS: Whole Exome Sequencing allowed dual molecular diagnoses: de novo TP63-related syndromic ectrodactyly and familial CNGB3-related congenital cone dystrophy.

Contact lens wear and follow-up and its association with signs and symptoms of meibomian gland dysfunction.

INTRODUCTION: This study investigated the equivocal association between contact lens (CL) wear and meibomian gland dysfunction (MGD) by comparing the morphological, functional and subjective outcomes of CL wearers versus control, non-CL wearers. CL wearers were examined as two cohorts based on the annual attendance of follow-up visits (FLU-attended these visits, whereas non-FLU did not). METHODS: Habitual logMAR visual acuity, invasive and non-invasive tear break-up time, Schirmer test, Efron grading scales, meibum quality score (MQS), meibum expressibility score (MES), meibomian gland (MG) loss, lid margin abnormalities and subjective dry eye (DE) symptoms were assessed. RESULTS: Of the 128 participants, 31 were in the FLU cohort, 43 were in the non-FLU cohort and 54 were controls (mean ages: 22.2 ± 3.1, 23.0 ± 4.6 and 22.3 ± 3.5, respectively). Non-FLU CL wearers had more symptoms than controls (3.7 ± 2.4 vs. 2.3 ± 2.1, p < 0.01). Morphologically, FLU (16.9 ± 8.8%, p = 0.02) and non-FLU (18.6 ± 11.3%, p = 0.001) had more MG loss than controls (11.2 ± 6.8%). Functionally, FLU (0.6 ± 0.7, p = 0.01) and non-FLU (0.8 ± 0.9, p = 0.001) had worse MES than controls (0.2 ± 0.5). FLU and non-FLU were both associated with corneal staining (odds ratio [OR] = 3.42, 95% CI: 1.16-10.11, p = 0.03 and OR = 5.23, 95% CI: 1.89-14.48, p = 0.001, respectively) and MG loss (OR = 10.47, 95% CI: 1.14-96.29, p = 0.04 and OR = 16.63, 95% CI: 1.96-140.86, p = 0.01, respectively). Non-FLU CL wear was also associated with abnormal MQS (OR = 12.87, 95% CI: 1.12-148.41, p = 0.04), conjunctival staining (OR = 12.18, 95% CI: 3.66-40.51, p < 0.001) and lid margin telangiectasia (OR = 3.78, 95% CI: 1.55-9.21, p = 0.003). MGD was three times more prevalent in CL wearers (12%) than in controls (4%). CONCLUSIONS: Both CL-wearing cohorts demonstrated significantly more MG abnormalities than controls though the difference was not clinically significant. Non-FLU CL wearers had more DE symptoms. Non-FLU CL wear is an independent predictor for more abnormalities than FLU CL wear, emphasising the importance of follow-ups.

Instability of tear film and loss of meibomian glands in patients with acne vulgaris / Instabilidade do filme lacrimal e perda de glândulas meibomianas em pacientes com acne vulgaris

ABSTRACT Purpose: In this prospective study, we compared ocular clinical variables in patients with acne vulgaris with those of healthy controls. These variables included tear film break-up time, meibomian gland dropout rate, and anterior chamber parameters. Methods: Our sample comprised 73 eyes from 73 patients with acne vulgaris and 67 eyes from 67 healthy controls. All participants underwent a non-invasive first tear film break-up time test and the average tear film break-up time was evaluated. Meibography was used to identify any meibomian gland dropout. The parameters of the cornea and anterior chamber were measured using Scheimpflug topography imaging. Finally, the ocular surface disease index questionnaire was administered to score each participant on their subjective experience of ocular complaints. Results: The noninvasive first tear film break-up time values of the acne vulgaris Group and the control Group were 4.7 ± 2.8 and 6.4 ± 3.5 sec, respectively. There was a significant difference between the groups (p=0.016). The number of eyes with tear break-up at any time during the measurement period was also significantly higher in the acne Group (p=0.018). In the acne vulgaris Group, the mean meibomian gland dropout rates were 33.21 ± 15.5% in the upper lids and 45.4 ± 14.5% in the lower lids. In the control group, these rates were 15.7 ± 6.9% and 21 ± 9.7% respectively. Dropout was significantly higher in the acne group for both the upper and lower lids (p=0.000). Conclusion: We found impaired tear stability in patients with acne vulgaris and a high rate of meibomian gland dropout. These glands play a key role in tear stability and their dropout is likely to result in evaporative dry eye. Measurement of the variables in this study allows objective diagnosis of this condition using a non-invasive, dye-free methodology, with minimum contact.

RESUMO Objetivo: Neste estudo prospectivo, pacientes com acne vulgaris e indivíduos saudáveis do grupo controle foram comparados em relação ao tempo de ruptura do filme lacrimal, taxa de abandono de glândulas meibomianas e parâmetros da câmara anterior, usando o tempo de ruptura do filme lacrimal topográfico não invasivo, meibografia não invasiva e fotografia de Scheimpflug, respectivamente. Métodos: Setenta e três olhos de 73 pacientes com acne vulgaris e 67 olhos de 67 indivíduos saudáveis foram incluídos. Todos os participantes submetidos ao primeiro tempo de ruptura do filme lacrimal não-invasivo e ao tempo médio de ruptura do filme lacrimal não-invasivo foram avaliados pelo uso do tempo de ruptura do filme lacrimal; perda de glândulas meibomianas foram avaliadas por meibografia; os parâmetros da córnea e da câmara anterior foram medidos por fotografia de Scheimpflug; e, finalmente, as queixas oculares subjetivas foram pontuadas com o uso do questionário do Indice de doenças de superfície ocular. Resultados: Os valores do tempo de ruptura do primeiro filme lacrimal não-invasivo do Grupo com acne vulgaris e do Grupo controle foram 4,7 ± 2,8 e 6,4 ± 3,5 segundos, respectivamente, refererindo-se a uma diferença significativa entre os valores dos grupos (p=0,016). Qualitativamente, o número de olhos com ruptura lacrimal a qualquer momento durante o período de medição foi significativamente maior no grupo de pacientes. (p=0,018). No Grupo com acne vulgaris, a perda de glândulas meibomianas nas pálpebras superiores foi de 33,21 ± 15,5% e nas pálpebras inferiores foi de 45,4 ± 14,5%; por outro lado, no Grupo controle foi de 15,7 ± 6,9% e 21 ± 9,7% respectivamente; ambos os casos referem-se a uma diferença significativa entre os grupos (p=0,000). Conclusão: Encontramos estabilidade comprometida do filme lacrimal em pacientes com acne vulgaris. No entanto, o comprometimento foi de grau muito menor, em comparação com a taxa de perda das glândulas meibomianas que desempenham um papel fundamental na estabilidade do filme lacrimal. Esta condição pode ser documentada de forma objetiva - uma metodologia parcialmente sem contato, totalmente não-invasiva e livre de corantes.

Evaluation of Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum

ABSTRACT Purpose: To assess Meibomian gland dysfunction using meibography in patients with xeroderma pigmentosum and correlate with ocular surface changes. Methods: This cross-sectional study evaluated patients with xeroderma pigmentosum. All patients underwent a comprehensive and standardized interview. The best-corrected visual acuity of each eye was determined. Detailed ophthalmic examination was conducted, including biomicroscopy examination of the ocular surface, Schirmer test type I, and meibography, and fundus examination was also performed when possible. Meibomian gland dysfunction was assessed by non-contact meibography using Oculus Keratograph® 5M (OCULUS Inc., Arlington, WA, USA). Saliva samples were collected using the Oragene DNA Self-collection kit (DNA Genotek Inc., Ottawa, Canada), and DNA was extracted as recommended by the manufacturer. Factors associated with abnormal meiboscores were assessed using generalized estimating equation models. Results: A total of 42 participants were enrolled, and 27 patients underwent meibography. The meiboscore was abnormal in the upper eyelid in 8 (29.6%) patients and in the lower eyelid in 17 (62.9%). The likelihood of having abnormal meiboscores in the lower eyelid was 16.3 times greater than that in the upper eyelid. In the final multivariate model, age (p=0.001), mutation profile (p=0.006), and presence of ocular surface malignant tumor (OSMT) (p=0.014) remained significant for abnormal meiboscores. For a 1-year increase in age, the likelihood of abnormal meiboscores increased by 12%. Eyes with OSMT were 58.8 times more likely to have abnormal meiboscores than eyes without ocular surface malignant tumor. Conclusion: In the final model, age, xeroderma pigmentosum profile, previous cancer, and clinical alterations on the eyelid correlated with a meiboscore of ≥2. Meibomian gland dysfunction was common in patients with xeroderma pigmentosum, mainly in the lower eyelid. The severity of Meibomian gland dysfunction increases with age and is associated with severe eyelid changes.

Dupilumab-Associated Blepharoconjunctivitis: Clinical and Morphological Aspects.

PURPOSE: To describe the clinical and morphologic changes in the ocular surface microstructure of patients affected with moderate-to-severe Atopic Dermatitis (AD) before and during Dupilumab treatment. METHODS: This is a monocentric observational study on thirty-three patients affected with AD before and during Dupilumab treatment. All patients underwent a slit-lamp examination: complete clinical assessment, Break Up Time test (BUT), Schirmer test, and corneal staining grading (Oxford scale) were performed. Meibomian Glands Dysfunction (MGD) evaluation (Meibography), Non-invasive Keratograph Break Up Time test (NIKBUT), Tear Meniscus Height (TMH), and ocular Redness Score (RS) have been investigated using an OCULUS Keratograph. In vivo images of the conjunctiva, cornea, and meibomian glands have been acquired by confocal microscopy. RESULTS: Sixty-six eyes were included in our study: twenty-two eyes of 11 naive patients with indication for treatment but not in therapy yet (Group 1) and forty-four eyes of 22 patients treated with Dupilumab for at least 4 months (subcutaneous administration of 300 mg every 2 weeks) (Group 2). Either patients treated with Dupilumab or naive patients with moderate-to-severe forms of AD had a tear film instability (TBUT and NIKBUT reduced), whereas the quantity of the tear film was overall normal (Schirmer test and TMH), without statistically significant differences between the two groups. When Meibography was performed with the Keratograph, the difference between Group 1 and Group 2 was statistically significant in terms of Meiboscore (p = 0.0043 and p = 0.0242, respectively), as well as the difference in terms of mean RS. These results paired well with the confocal microscopy results in which we found a decrease in the goblet cell population in the conjunctival epithelium in the treated group (5.2 cells/mm), along with inflammatory cells that were more concentrated around the adenoid lumina of the meibomian glands. CONCLUSIONS: In recent years, the use of Dupilumab has been increasing, but mild-to-severe conjunctivitis is a common side effect. Our major results demonstrate a loss of meibomian glands at the Keratograph examination: we can assume a reduced meibum secretion and an evaporative dry eye with MGD. We suggest that the inflammation of the ocular surface may involve not only the cornea and the conjunctiva, but also the meibomian glands, and Dupilumab may play a role. However, the frequency of clear conjunctivitis is not as common as reported in the literature.

A Deep Learning Approach for Meibomian Gland Appearance Evaluation.

Purpose: To develop and evaluate a deep learning algorithm for Meibomian gland characteristics calculation. Design: Evaluation of diagnostic technology. Subjects: A total of 1616 meibography images of both the upper (697) and lower (919) eyelids from a total of 282 individuals. Methods: Images were collected using the LipiView II device. All the provided data were split into 3 sets: the training, validation, and test sets. Data partitions used proportions of 70/10/20% and included data from 2 optometry settings. Each set was separately partitioned with these proportions, resulting in a balanced distribution of data from both settings. The images were divided based on patient identifiers, such that all images collected for one participant could end up only in one set. The labeled images were used to train a deep learning model, which was subsequently used for Meibomian gland segmentation. The model was then applied to calculate individual Meibomian gland metrics. Interreader agreement and agreement between manual and automated methods for Meibomian gland segmentation were also carried out to assess the accuracy of the automated approach. Main Outcome Measures: Meibomian gland metrics, including length ratio, area, tortuosity, intensity, and width, were measured. Additionally, the performance of the automated algorithms was evaluated using the aggregated Jaccard index. Results: The proposed semantic segmentation-based approach achieved average aggregated Jaccard index of mean 0.4718 (95% confidence interval [CI], 0.4680-0.4771) for the 'gland' class and a mean of 0.8470 (95% CI, 0.8432-0.8508) for the 'eyelid' class. The result for object detection-based approach was a mean of 0.4476 (95% CI, 0.4426-0.4533). Both artificial intelligence-based algorithms underestimated area, length ratio, tortuosity, widthmean, widthmedian, width10th, and width90th. Meibomian gland intensity was overestimated by both algorithms compared with the manual approach. The object detection-based algorithm seems to be as reliable as the manual approach only for Meibomian gland width10th calculation. Conclusions: The proposed approach can successfully segment Meibomian glands; however, to overcome problems with gland overlap and lack of image sharpness, the proposed method requires further development. The study presents another approach to utilizing automated, artificial intelligence-based methods in Meibomian gland health assessment that may assist clinicians in the diagnosis, treatment, and management of Meibomian gland dysfunction. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.