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CD4+ cytotoxic T lymphocytes (CTLs) were recently implicated in immune-mediated inflammation and fibrosis progression of Graves' orbitopathy (GO). However, little is known about therapeutic targeting CD4+ CTLs. Herein, we studied the effect of rapamycin, an approved mammalian target of rapamycin complex 1(mTORC1) inhibitor, in GO mouse model, in vitro and in refractory GO patients. In the adenovirus-induced model, rapamycin significantly decreased the incidence of GO. This was accompanied by reduction of both CD4+ CTLs, as well as reduction of orbital inflammation, adipogenesis and fibrosis. CD4+CTLs from active GO patients showed upregulation of mTOR pathway, while rapamycin decreased their proportions and cytotoxic function. Low-dose rapamycin treatment substantially improved diplopia and clinical activity score in steroid-refractory GO patients. Single-cell RNA sequencing revealed that eye motility improvement was closely related to suppression of inflammation and chemotaxis in CD4+ CTLs. In conclusion, rapamycin is a promising treatment for CD4+ CTL-mediated inflammation and fibrosis in GO.

Purpose Verruca Vulgaris is a common benign cutaneous lesion which only reported occasionally to have malignant potential. Our purpose is to report a rare case of verruca vulgaris involving the eyelid and subsequently transformed into the combination of squamous cell carcinoma and basal cell carcinoma. Observations We reported a case of a 97-year-old female with a chronic biopsy proven verruca vulgaris involving the left lateral canthus. She presented with pain and swelling 5 years after the biopsy. Physical examination showed a painful warty crushed growth mass surrounded by erythematous skin changes, sized 40 × 40mm. Excisional biopsy showed squamous cell carcinoma and a microscopic focus of basal cell carcinoma. Conclusions and importance Our case demonstrates the oncogenic potential of verruca vulgaris into the combination of squamous cell carcinoma and basal cell carcinoma within one lesion. Size, chronicity and UV radiation may increase the risk of malignancy. Early surgical excision should be considered in eyelid involving chronic verruca vulgaris.

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BackgroundOral corticosteroid remains the first-line treatment of IgG4-related ophthalmic disease, but steroid-dependence is common and serious. Factors associated with steroid dependence and relapse have to be further explored.Study populationA city-wide, biopsy-proven, Chinese cohort.MethodsRetrospective, masked review of medical records, orbital images and histopathology reports.ResultsThere were 101 patients with at least 24-month follow-up. Up to 82% (82/101) received oral corticosteroid as first-line treatments, and 7 of them received also concomitant steroid-sparing agents (SSA)/biological agents as primary treatment. There was 61% (50/82) of patients required long-term corticosteroid (alone=23, with SSA=27) after 1.9±0.7 (range 1–5) relapses. When compared with the 21% (17/82) of patients who tapered corticosteroid successfully for 24 months, steroid dependence was associated with elevated baseline serum IgG4 level (94% vs 65%, p<0.01) and Mikulicz syndrome (46% vs 18%, p<0.05). Up to 13% (11/82) of patients tolerated residual disease after tapering off corticosteroid. There was 17% (17/101) of patients did not require any medications after biopsies. They were more likely to have debulking surgeries (71% vs 40%, p<0.05), discrete orbital lesions (65% vs 26%, p<0.05), normal baseline serum IgG4 level (24% vs 6%, p<0.05) and no Mikulicz syndrome (94% vs 61%, p<0.05).ConclusionIn this cohort, 60% of patients required long-term maintenance oral corticosteroid. Elevated pretreatment serum IgG4 level and Mikulicz syndrome were associated with steroid dependence. Debulking surgery is an alternative for a subgroup of patients with discrete orbital lesions, normal baseline IgG4 level and no Mikulicz syndrome.

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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 (β = −1.13, 95%CI: −2.08, −0.18) and severe MGD in the lower eyelid (β = −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.

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