Hepatocyte-macrophage crosstalk via the PGRN-EGFR axis modulates ADAR1-mediated immunity in the liver.

ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss. Ifih1;Adar double KO (dKO) hepatocytes accumulate endogenous dsRNAs, leading to aberrant transition to a highly inflammatory state and recruitment of macrophages into dKO livers. Mechanistically, progranulin (PGRN) appears to mediate ADAR1 deficiency-induced liver pathology, promoting interferon signaling and attracting epidermal growth factor receptor (EGFR)+ macrophages into dKO liver, exacerbating hepatic inflammation. Notably, the PGRN-EGFR crosstalk communication and consequent immune responses are significantly repressed in ADAR1high tumors, revealing that pre-neoplastic or neoplastic cells can exploit ADAR1-dependent immune tolerance to facilitate immune evasion.

Epidemiology of thyroid-stimulating immunoglobulin in recent-onset symptomatic thyroid eye disease.

Purpose: This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients. Methods: A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI. Results: A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60-0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP. Conclusion: TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

Investigation of lacrimal gland and extraocular muscle in thyroid eye disease patients with severe subjective dry eye disease: a multiparametric magnetic resonance imaging study.

PURPOSE: To analyze the radiological features of the lacrimal gland (LG) and extraocular muscle (EOM) in thyroid eye disease (TED) patients with severe subjective dry eye disease (DED) using magnetic resonance imaging (MRI) measurements. METHODS: In this cross-sectional study, mechanical ocular exposure, dry eye assessment and MRI data were collected. Patients were classified into non-severe subjective DED group with ocular surface disease index (OSDI) < 33 and severe subjective DED group with OSDI ≥ 33. Linear regression model was applied for comparing the OSDI < 33 and OSDI ≥ 33 group in TED patients. The predictive performance of MRI parameters and models was assessed by receiver operating characteristic curve (ROC) analysis. RESULTS: Consecutive 88 TED patients (176 eyes) were included in this study. In the OSDI < 33 group, 52 TED patients (104 eyes) with a mean clinical activity score (CAS) of 0.63 ± 0.75. In the OSDI ≥ 33 group, there are 36 TED patients (72 eyes), with a mean CAS of 1.50 ± 1.54. The age and sex of the patients were matched between the two groups. The OSDI ≥ 33 group had shorter tear break-up time, larger levator palpebrae superioris / superior rectus (LPS/SR), inferior rectus and lateral rectus, smaller LG, more inflammatory LPS/SR and inferior rectus than OSDI < 33 DED group (P < 0.05). In the linear regression analysis, compare to the OSDI < 33 DED group, the OSDI ≥ 33 group had larger medial rectus cross-sectional area (ß = 0.06, 95%CI: (0.02, 0.10), P = 0.008), larger inferior rectus cross-sectional area (ß = 0.06, 95%CI: (0.00, 0.12), P = 0.048), smaller LG cross-sectional area (ß = -0.14, 95%CI: (-0.25, -0.04), P = 0.008). In the ROC analysis, the area under curve of medial rectus, inferior rectus, LG, and combined model are 0.625, 0.640, 0.661 and 0.716, respectively. CONCLUSION: Multiparametric MRI parameters of the LG and EOM in TED patients with severe subjective DED were significantly altered. Novel models combining the cross-sectional area of LG, medial rectus and inferior rectus showed good predictive performance in TED patients with severe subjective DED.

Ocular surface and meibomian gland evaluation in euthyroid Graves' ophthalmopathy.

PURPOSE: Euthyroid Graves' ophthalmology (EGO) refers to the subgroup of thyroid eye disease patients with distinct clinical presentations. This study evaluated the ocular surface and meibomian gland changes in EGO patients. METHODS: A cross-sectional study was conducted at The Chinese University of Hong Kong including 34 EGO patients and 34 age-and sex- matched healthy controls. Outcome measures include anterior segment examination, keratographic and meibographic imaging. RESULTS: Between 34 EGO patients and 34 age and sex-matched healthy controls, EGO was associated with a higher ocular surface disease index (P < 0.01), higher severity of meibomian gland dropout (upper: P < 0.001, lower: P < 0.00001) and higher percentage of partial blinking (P = 0.0036). The worse affected eyes of the EGO patients were associated with corneal staining (P = 0.0019), eyelid telangiectasia (P = 0.0009), eyelid thickening (P = 0.0013), eyelid irregularity (P = 0.0054), meibomian gland plugging (P < 0.00001), expressibility (P < 0.00001), and meibum quality (P < 0.00001). When the two eyes of the same EGO patient were compared, the degree of meibomian gland dropout was higher among the worse affected eyes (upper: P < 0.00001, and lower: P < 0.00001). Tear meniscus height, lipid layer thickness, and noninvasive break-up time were comparable between the two eyes of EGO patients and also between EGO patients and healthy controls. TMH was positively correlated with the degree of exophthalmos (r = 0.383, P < 0.05). CONCLUSION: EGO patients have more ocular surface complications and meibomian gland dropouts than healthy controls. Almost 60% of them had dry eye symptoms, but aqueous deficiency was not apparent. Further studies are warranted to clarify the mechanism of dry eye in EGO. (249 words).

Euthyroid graves' ophthalmopathy in a Chinese population: A cross-sectional follow-up study.

OBJECTIVES: A subtype of patients with thyroid eye disease (TED) were found to be euthyroid without prior thyroid dysfunction or treatment, known as Euthyroid Graves' Ophthalmopathy (EGO). We report the prevalence, clinical and serological phenotypes of EGO in a Chinese population. METHODS: A cross-sectional follow-up study. Ethnic Chinese TED patients were managed at the Thyroid Eye Clinic(TEC), Prince of Wales Hospital and TEC, the Chinese University of Hong Kong between September 2007 and July 2021. RESULTS: A total of 66 (5%) patients among the 1266 ethnic Han Chinese TED cohort were diagnosed as EGO, and 6 (9%)of them become dysthyroid over an average of 74-month follow-up. EGO patients were associated with a longer duration between onset of the symptoms to our first consultation (P < 0.0001), a higher male-to-female ratio (P = 0.0045) and a higher age of disease onset (P = 0.0092). Family history of thyroid disease was more common in TED patients (P = 0.0216) than in EGO patients. EGO patients were more likely to present unilaterally (P < 0.0001), and they have a larger difference in MRD1 (P < 0.0001), and extraocular motility (P < 0.0001) between the 2 eyes when compared to the TED patients. Notably, the extraocular motility restriction of the worst eye was more affected in EGO patients (P = 0.0113). The percentages of patients who received IVMP, ORT and emergency or elective surgeries(decompression or squint operation) between EGO and TED were similar. CONCLUSIONS: Understanding the important clinical phenotypes of EGO may help the clinician to make the correct diagnosis. Further study to compare EGO and TED is warranted.

An essential protease, FtsH, influences daptomycin resistance acquisition in Enterococcus faecalis.

Daptomycin is a last-line antibiotic commonly used to treat vancomycin-resistant Enterococci, but resistance evolves rapidly and further restricts already limited treatment options. While genetic determinants associated with clinical daptomycin resistance (DAPR) have been described, information on factors affecting the speed of DAPR acquisition is limited. The multiple peptide resistance factor (MprF), a phosphatidylglycerol-modifying enzyme involved in cationic antimicrobial resistance, is linked to DAPR in pathogens such as methicillin-resistant Staphylococcus aureus. Since Enterococcus faecalis encodes two paralogs of mprF and clinical DAPR mutations do not map to mprF, we hypothesized that functional redundancy between the paralogs prevents mprF-mediated resistance and masks other evolutionary pathways to DAPR. Here, we performed in vitro evolution to DAPR in mprF mutant background. We discovered that the absence of mprF results in slowed DAPR evolution and is associated with inactivating mutations in ftsH, resulting in the depletion of the chaperone repressor HrcA. We also report that ftsH is essential in the parental, but not in the ΔmprF, strain where FtsH depletion results in growth impairment in the parental strain, a phenotype associated with reduced extracellular acidification and reduced ability for metabolic reduction. This presents FtsH and HrcA as enticing targets for developing anti-resistance strategies.

Unsupervised spatially embedded deep representation of spatial transcriptomics.

Optimal integration of transcriptomics data and associated spatial information is essential towards fully exploiting spatial transcriptomics to dissect tissue heterogeneity and map out inter-cellular communications. We present SEDR, which uses a deep autoencoder coupled with a masked self-supervised learning mechanism to construct a low-dimensional latent representation of gene expression, which is then simultaneously embedded with the corresponding spatial information through a variational graph autoencoder. SEDR achieved higher clustering performance on manually annotated 10 × Visium datasets and better scalability on high-resolution spatial transcriptomics datasets than existing methods. Additionally, we show SEDR's ability to impute and denoise gene expression (URL: https://github.com/JinmiaoChenLab/SEDR/ ).

Purine and carbohydrate availability drive Enterococcus faecalis fitness during wound and urinary tract infections.

IMPORTANCE: Although E. faecalis is a common wound pathogen, its pathogenic mechanisms during wound infection are unexplored. Here, combining a mouse wound infection model with in vivo transposon and RNA sequencing approaches, we identified the E. faecalis purine biosynthetic pathway and galactose/mannose MptABCD phosphotransferase system as essential for E. faecalis acute replication and persistence during wound infection, respectively. The essentiality of purine biosynthesis and the MptABCD PTS is driven by the consumption of purine metabolites by E. faecalis during acute replication and changing carbohydrate availability during the course of wound infection. Overall, our findings reveal the importance of the wound microenvironment in E. faecalis wound pathogenesis and how these metabolic pathways can be targeted to better control wound infections.

Systemic Involvement in Immunoglobulin G4-Related Ophthalmic Disease.

BACKGROUND: Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) poses clinical challenges due to its heterogeneous ocular and systemic manifestations. We aim to report the systemic involvement and the clinical, serological and radiological associations of a cohort of Chinese patients. METHODS: A territory-wide, biopsy-proven, Chinese cohort. A retrospective, masked chart review of medical records, orbital images, and histopathology reports. RESULTS: A total of 122 (65 male) patients with a follow-up of 81 ± 49 (24 to 84) months were reviewed. Ninety (74%) patients presented bilaterally. Subacute upper eyelid swelling was the commonest presentation (82/122, 67%). During follow-up, 91/122 patients (75%) underwent extra-orbital imaging including computer tomography (692 films), ultrasonography (182 films), magnetic resonance imaging (76 films) and whole body FDG-PET scan (33 films). Eighty-six (95%) of these 91 patients had extra-orbital involvement radiologically (2.7 ± 1.6 regions, range: 0 to 9). Lymph node was the most prevalent (N = 60,66%), followed by salivary gland (N = 51,56%), lung (N = 49,54%), kidney (N = 22, 24%), hepatobiliary tree (N = 18, 20%) and pancreas (N = 17, 19%). Other organs include thyroid, aorta, meninges/brain and skin. Twenty-eight (23%) patients had allergic diseases (19 asthma, 16 allergic rhinitis, and 6 eczemas). Fifty-seven (48%) patients had paranasal sinusitis. Serum eosinophilia was associated with a higher number (3.24 versus 2.52, P = 0.0304) of organ involvement. Patients with deep organ involvement was associated with a higher age of IgG4-ROD onset (70 ± 12 versus 56 ± 13, P < 0.0001). CONCLUSIONS: 95% of the patients who underwent systemic imaging in our cohort had systemic organ involvement. An early physicians' assessment and radiological imaging are recommended after the diagnosis of IgG4-ROD.

Diagnostic methods for dysthyroid optic neuropathy: A systematic review and analysis.

Diagnosis of dysthyroid optic neuropathy (DON) typically relies on a set of diagnostic clinical features, including decreased visual acuity, impaired color vision, presence of relative afferent pupillary defect, optic disc swelling and ancillary tests including visual field (VF), pattern visual evoked potential (pVEP), and apical crowding or optic nerve stretching on neuroimaging. We summarize various diagnostic methods to establish or rule out DON. A total of 95 studies (involving 4619 DON eyes) met the inclusion criteria. All of the studies considered clinical features as evidence of DON, while most of the studies confirmed DON diagnosis by combining clinical features with ancillary tests. Forty studies (42.1%) used at least 2 out of the 3 tests (VF, pVEP and neuroimaging) and 13 studies (13.7%) used all 3 tests to diagnose DON. In 64 % of the published studies regarding DON, the diagnostic methods of DON were not specified. It is important to note the limitations of relying solely on clinical features for diagnosing DON. On the other hand, since some eyes with optic neuropathy can be normal in one ancillary test, but abnormal in another, using more than one ancillary test to aid diagnosis is crucial and should be interpreted in correlation with clinical features. We found that the diagnostic methods of DON in most studies involved using a combination of specific clinical features and at least 2 ancillary tests.

Enterococcus faecalis suppresses Staphylococcus aureus-induced NETosis and promotes bacterial survival in polymicrobial infections.

Enterococcus faecalis is an opportunistic pathogen that is frequently co-isolated with other microbes in wound infections. While E. faecalis can subvert the host immune response and promote the survival of other microbes via interbacterial synergy, little is known about the impact of E. faecalis-mediated immune suppression on co-infecting microbes. We hypothesized that E. faecalis can attenuate neutrophil-mediated responses in mixed-species infection to promote survival of the co-infecting species. We found that neutrophils control E. faecalis infection via phagocytosis, ROS production, and degranulation of azurophilic granules, but it does not trigger neutrophil extracellular trap formation (NETosis). However, E. faecalis attenuates Staphylococcus aureus-induced NETosis in polymicrobial infection by interfering with citrullination of histone, suggesting E. faecalis can actively suppress NETosis in neutrophils. Residual S. aureus-induced NETs that remain during co-infection do not impact E. faecalis, further suggesting that E. faecalis possess mechanisms to evade or survive NET-associated killing mechanisms. E. faecalis-driven reduction of NETosis corresponds with higher S. aureus survival, indicating that this immunomodulating effect could be a risk factor in promoting the virulence polymicrobial infection. These findings highlight the complexity of the immune response to polymicrobial infections and suggest that attenuated pathogen-specific immune responses contribute to pathogenesis in the mammalian host.

A Bacterial Quorum Sensing Regulated Protease Inhibits Host Immune Responses by Cleaving Death Domains of Innate Immune Adaptors.

Innate immune adaptor proteins are critical components of the innate immune system that propagate pro-inflammatory responses from their upstream receptors, and lead to pathogen clearance from the host. Bacterial pathogens have developed strategies to survive inside host cells without triggering the innate immune surveillance in ways that are still not fully understood. Here, it is reported that Pseudomonas aeruginosa induces its quorum sensing mechanism after macrophage engulfment. Further investigation of its secretome identified a quorum sensing regulated product, LasB, is responsible for innate immune suppression depending on the MyD88-mediated signaling. Moreover, it is showed that this specific type of pathogen-mediated innate immune suppression is due to the enzymatic digestion of the death domains of the innate immune adaptors, mainly MyD88, and attributed to LasB's large substrate binding groove. Lastly, it is demonstrated that the secretion of LasB from P. aeruginosa directly contributed to MyD88 degradation within macrophages. Hence, it is discovered an example of bacterial quorum sensing-regulated cellular innate immune suppression by direct cleavage of immune adaptors.

Ocular Surface Evaluation in Immunoglobulin G4-Related Ophthalmic Disease.

PURPOSE: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. DESIGN: Cross-sectional, matched case-control comparison study. METHODS: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. RESULTS: A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = -0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = -0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). CONCLUSIONS: IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

Magnetic resonance imaging parameters on lacrimal gland in thyroid eye disease: a systematic review and meta-analysis.

BACKGROUND: Thyroid eye disease is an extrathyroidal manifestation of Graves' disease and is associated with dry eye disease. This is the first systematic review and meta-analysis to evaluate the role of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease diagnosis, activity grading, and therapeutic responses prediction. METHODS: Up to 23 August, 2022, 504 studies from PubMed and Cochrane Library were analyzed. After removing duplicates and imposing selection criteria, nine eligible studies were included. Risk of bias assessment was done. Meta-analyses were performed using random-effect model if heterogeneity was significant. Otherwise, fixed-effect model was used. Main outcome measures include seven structural magnetic resonance imaging parameters (lacrimal gland herniation, maximum axial area, maximum coronal area, maximum axial length, maximum coronal length, maximum axial width, maximum coronal width), and three functional magnetic resonance imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-apparent diffusion coefficient or mean diffusivity, diffusion-weighted imaging-apparent diffusion coefficient). RESULTS: Thyroid eye disease showed larger maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width, diffusion tensor imaging-apparent diffusion coefficient/ mean diffusivity, and lower diffusion tensor imaging-fractional anisotropy than controls. Active thyroid eye disease showed larger lacrimal gland herniation, maximum coronal area, diffusion-weighted imaging-apparent diffusion coefficient than inactive. Lacrimal gland dimensional (maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width) and functional parameters (diffusion tensor imaging-apparent diffusion coefficient, diffusion tensor imaging-apparent diffusion coefficient) could be used for diagnosing thyroid eye disease; lacrimal gland herniation, maximum coronal area, and diffusion-weighted imaging-apparent diffusion coefficient for differentiating active from inactive thyroid eye disease; diffusion tensor imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-mean diffusivity) and lacrimal gland herniation for helping grading and therapeutic responses prediction respectively. CONCLUSIONS: Magnetic resonance imaging lacrimal gland parameters can detect active thyroid eye disease and differentiate thyroid eye disease from controls. Maximum coronal area is the most effective indicator for thyroid eye disease diagnosis and activity grading. There are inconclusive results showing whether structural or functional lacrimal gland parameters have diagnostic superiority. Future studies are warranted to determine the use of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease.

Burnishing of exposed porous polyethylene orbital implant: is it useful?

OBJECTIVE: To describe and report the surgical outcomes of the burnishing technique for exposed porous polyethylene (PP) orbital implants. METHODS: A retrospective review of consecutive patients who underwent repair of an exposed PP orbital implant at Hong Kong Eye Hospital and Queen Elizabeth Hospital, Hong Kong, between January 2002 and April 2022 was conducted. Exposed PP orbital implants were burnished with an electric drill. The exposed area was then covered by a donor scleral graft followed by conjunctival wound closure. Patients with a shallow lower eyelid fornix would undergo additional fornix deepening procedures that mobilize the conjunctiva and provide adequate coverage of the implant. RESULTS: Six patients who had exposed PP orbital implants following enucleation (n = 4) and evisceration (n = 2) underwent repair. Five of the six patients did not experience any recurrence at an average follow-up of 25 months (range, 7-42 months). One patient who suffered from endophthalmitis experienced orbital implant re-exposure 16 months after the revision was managed by reimplantation of an acrylic implant and wrapping with both donor scleral graft and dermis fat graft. CONCLUSION: In conclusion, we described a burnishing technique for repairing exposed PP orbital implants. Our technique is effective in preventing implant re-exposure and is easy to perform.

Investigating the Impact of COVID-19 Infection on Dry Eye Parameters.

PURPOSE: This study aims to compare dry eye parameters before and after COVID-19 infection in dry eye patients. METHODS: We included 44 dry eye patients (88 eyes) from our existing dry eye cohort, with 22 belonging to the post-COVID-19 group due to a prior COVID-19 infection and the other 22 forming the non-COVID-19 group as they had no history of COVID-19. We examined and compared the dry eye parameters of the post-COVID-19 group, including the ocular surface disease index (OSDI), Schirmer's test results (ST), non-invasive Keratography tear break-up time (NIKBUT), lipid layer thickness (LLT), Meibomian gland dysfunction (MGD), and the grading of papillae and follicles, both before and after the COVID-19 infection. We also compared the dry eye parameters difference of the post-COVID-19 group with the non-COVID-19 group. RESULTS: The post-COVID-19 group was comprised of individuals with an average age of 38.36 ± 14.99 years, of which 82% were female. The time interval between the two tests was 16.92 ± 5.40 months, which did not differ significantly from the non-COVID-19 group. Compared to the pre-COVID-19 eyes, the post-COVID-19 eyes showed a significant decrease in the average LLT (52.86 ± 18.00 nm vs. 63.00 ± 22.40 nm, p < 0.001), as well as the maximum LLT (67.89 ± 20.81 nm vs. 78.48 ± 20.55 nm, p < 0.001). The MGD in both the upper (1.75 ± 0.84) and lower eyelids (1.43 ± 0.73) worsened after a COVID-19 infection. Additionally, the grading of papillae was worse following a COVID-19 infection (0.61 ± 0.69 vs. 0.16 ± 0.37, p < 0.001). The multivariate linear regression model revealed a negative association between COVID-19 infection and NIKBUT-average (ß = -2.98, 95%CI: (-5.82, -0.15), p = 0.039), LLT-average (ß = -14.12, 95%CI: (-22.66, -5.59), p = 0.001), and LLT max (ß = -15.65, 95%CI: (-23.09, -8.20), p < 0.001). CONCLUSION: From preliminary results, we concluded that dry eye patients who have been infected with COVID-19 appear to have a more severe dry eye condition, as evidenced by lower LLT, worse papillae and MGD, and shorter NIKBUT. It is important to raise awareness of this potential long-term symptom of COVID-19, especially among existing dry eye patients.

Ocular Surface Changes in Treatment-Naive Thyroid Eye Disease.

OBJECTIVE: To investigate the association of meibomian gland dysfunction (MGD) and ocular surface exposure with tear film instability in untreated thyroid eye disease (TED) patients. METHODS: A cross-sectional study of TED patients from September 2020 to September 2022 was conducted. Ocular surface parameters included ocular surface disease index (OSDI), tear meniscus height (TMH), non-invasive tear break-up time (NITBUT), partial blinking rate, lipid layer thickness (LLT), meibomian gland dropout (meiboscore), Schirmer's test, and corneal punctate epithelial erosions (PEE). Ocular surface exposure was assessed by the margin reflex distances of the upper and lower eyelid (MRD1 and MRD2), the amount of exophthalmos, lateral flare, and lagophthalmos. RESULTS: In total, 152 eyes from 76 TED patients (64 females and 12 males, age 42.99 ± 12.28 years) and 93 eyes from 61 healthy controls (51 females and 10 males, age 43.52 ± 17.93 years) were examined. Compared with control eyes, TED eyes had higher OSDI, TMH, LLT, and PEE; shorter NITBUT; and worse meiboscore (all p < 0.05). They also had larger amounts of exophthalmos, longer MRD1, more lateral flare, and lagophthalmos. Multivariate analysis identified an association of the tear film instability with lagophthalmos (ß = -1.13, 95%CI: -2.08, -0.18) and severe MGD in the lower eyelid (ß = -5.01, 95%CI = -7.59, -2.43). CONCLUSIONS: Dry eye in TED is mainly manifested as evaporative dry eye disease. Severe lower eyelid MGD and worse lagophthalmos were significantly associated with tear film instability in treatment-naive TED patients.