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Graves disease represents a systemic autoimmune process targeting the thyroid, orbit, and pretibial skin. The thyroid dysfunction is treatable, but no consistently effective medical therapy has yet been described for the orbital manifestations of Graves disease, also known as thyroid-associated ophthalmopathy or thyroid eye disease. Several autoantigens are potentially relevant to the pathogenesis of thyroid eye disease. Activating antibodies generated against the thyrotropin receptor can be detected in a majority of patients, and these drive hyperthyroidism. However, stimulating antibodies against the insulin-like growth factor-1 receptor (IGF-1R) may also play a role in the extra-thyroid manifestations of GD. IGF-1R is over-expressed by orbital fibroblasts derived from patients with TED, while IGF-1R + T and IGF-1R + B cells are considerably more frequent in GD. Actions of several cytokines and the molecular interplay peculiar to the orbit appear to provoke the inflammation, fat expansion, and deposition of excessive extracellular matrix molecules in thyroid eye disease. Based upon these new insights, several therapeutic strategies can now be proposed that, for the first time, might specifically interrupt its pathogenesis.

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Corneal epithelial stem cells residing within the annular limbal crypts regulate adult tissue homeostasis. Autologous limbal grafts and tissue engineered corneal epithelial cell sheets have been widely used in the treatment of various ocular surface defects. In case of bilateral limbal defects, pluripotent stem cell (PSC) derived corneal epithelial cells are now being explored as an alternative to allogeneic limbal grafts. We report here an efficient method to generate complex three dimensional corneal organoids from human PSCs. The eye field primordial (EFP) clusters that emerged from differentiating PSCs developed into whole eye ball-like, self-organized, three dimensional, miniature structures consisting of retinal primordia (RP), corneal primordia (CP), primitive eye lid-like outer covering and ciliary margin zone-like adnexal tissues in a step-wise maturation process within 15 weeks. These minicorneal organoids recapitulate the early developmental events in vitro and displayed similar anatomical features and marker expression profiles as that of adult corneal tissues and offers an alternative tissue source for regenerating different layers of the cornea and eliminates the need for complicated cell enrichment procedures.

Acute dacryocystitis comprises 2.4% of all patients presenting with lacrimal system disorders. Fistula formation is a sequel more commonly seen with spontaneous rupture of a lacrimal abscess. The long-term outcomes in patients presenting with acute dacryocystitis are good with a surgical success rate of 94.3%.

PurposeDry eye syndrome is a multifactorial chronic disabling disease mainly caused by the functional disruptions in the lacrimal gland. The treatment involves palliation like ocular surface lubrication and rehydration. Cell therapy involving replacement of the gland is a promising alternative for providing long-term relief to patients. This study aimed to establish functionally competent lacrimal gland cultures in–vitro and explore the presence of stem cells in the native gland and the established in-vitro cultures.MethodsFresh human lacrimal gland from patients undergoing exenteration was harvested for cultures after IRB approval. The freshly isolated cells were evaluated by flow cytometry for expression of stem cell markers ABCG2, high ALDH1 levels and c-kit. Cultures were established on Matrigel, collagen and HAM and the cultured cells evaluated for the presence of stem cell markers and differentiating markers of epithelial (E-cadherin, EpCAM), mesenchymal (Vimentin, CD90) and myofibroblastic (α-SMA, S-100) origin by flow cytometry and immunocytochemistry. The conditioned media was tested for secretory proteins (scIgA, lactoferrin, lysozyme) post carbachol (100 µM) stimulation by ELISA.ResultsNative human lacrimal gland expressed ABCG2 (mean±SEM: 3.1±0.61%), high ALDH1 (3.8±1.26%) and c-kit (6.7±2.0%). Lacrimal gland cultures formed a monolayer, in order of preference on Matrigel, collagen and HAM within 15–20 days, containing a heterogeneous population of stem-like and differentiated cells. The epithelial cells formed ‘spherules’ with duct like connections, suggestive of ductal origin. The levels of scIgA (47.43 to 61.56 ng/ml), lysozyme (24.36 to 144.74 ng/ml) and lactoferrin (32.45 to 40.31 ng/ml) in the conditioned media were significantly higher than the negative controls (p<0.05 for all comparisons).ConclusionThe study reports the novel finding of establishing functionally competent human lacrimal gland cultures in-vitro. It also provides preliminary data on the presence of stem cells and duct-like cells in the fresh and in-vitro cultured human lacrimal gland. These significant findings could pave way for cell therapy in future.

Purpose To study the clinical and histopathological features of eyelid sebaceous gland carcinoma (SGC) and to evaluate the prognosis in the Asian-Indian population. Methods This is a retrospective study of 191 patients with SGC. Results The mean age at presentation of eyelid SGC was 57 years (median, 56 years). The tumor epicenter was most commonly located in the upper eyelid (n = 125, 65%). The mean tumor basal diameter was 15 mm (median, 10 mm). There was evidence of tumor extension into the orbit (n = 30, 16%), paranasal sinuses (n = 3, 2%), and brain (n = 1, 1%). Wide excision biopsy (n = 146, 78%) was the most common treatment modality. Tumor recurrence was noted in 42 (24%) patients over a mean follow-up period of 29 months (median, 20 months). On the basis of the Kaplan-Meier estimate, lymph node metastasis occurred in 18%, systemic metastasis was detected in 10%, and death occurred in 2% of patients at 10 years. On multivariate analysis, the factors predicting locoregional lymph node and systemic metastasis were medial canthal involvement (P = 0.004; P = 0.013), lateral canthal involvement (P = 0.013; P = 0.025), tumor basal diameter 410 mm (P = 0.002; P = 0.002), and perivascular invasion (P = 0.043; Po0.001), respectively. The factors predicting death due to metastasis on multivariate analysis were medial canthal involvement (P = 0.012) and tumor basal diameter 410 mm (P = 0.001). Conclusion Advanced eyelid SGC is a tumor associated with poor prognosis. In this study, canthal involvement, larger tumor diameter, and perivascular invasion were poor prognostic factors.

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