Graves’ ophthalmopathy (GO), or thyroid eye disease (TED), is the most frequent extrathyroidal manifestation of Graves’ disease (GD). Inflammation and subsequent aberrant tissue remodeling with fibrosis are important pathogenesis. There are many proposed mechanisms and molecular pathways contributing to tissue remodeling and fibrosis in GO, including adipogenesis, fibroblast proliferation and myofibroblasts differentiation, oxidative stress, endoplasmic reticulum (ER) stress, hyaluronan (HA) and glycosaminoglycans (GAGs) accumulation in the extracellular matrix (ECM) and new concepts of epigenetics modification, such as histone modification, DNA methylation, non-coding RNAs, and gut microbiome. This review summarizes the current understanding of ECM proteins and associated tissue remodeling in the pathogenesis and potential mediators for the treatment of GO.

Aims To determine long-term outcomes and risk factors for failure after mitomycin C (MMC)-augmented initial trabeculectomy (IT) in Taiwanese patients. Methods We reviewed medical records of patients with glaucoma undergoing IT during December 2006–December 2016. We defined complete success as an intraocular pressure (IOP) of >5 or ≤21 mm Hg or IOP reduction of ≥20% from baseline without supplemental medications and qualified success as the aforementioned IOP levels with or without supplemental medications. Kaplan-Meier survival and Cox proportional analyses evaluated success rates and risk factors for failure, respectively. Results We enrolled 190 patients (237 eyes; mean age: 54.0±15.3 years; mean postoperative follow-up period: 68.4±35.1 months). Mean IOP and glaucoma medications decreased from 22.2±10.8 to 14.4±5.2 mm Hg (p70 years had higher complete success rates than did those aged ≤70 years. Five cases (2.11%) exhibited bleb-associated complications. Conclusion Despite satisfactory long-term success rates, most eyes needed medication for IOP control, supporting the notion of predisposed scarring vitality in patients of Chinese ethnicity following MMC-augmented trabeculectomy.

Amniotic membrane (AM) has anti-inflammation, anti-fibrotic, and regenerative effects. Sutureless cryopreserved AM transplantation, ProKera^® (Bio-Tissue, Inc., Miami, FL, USA), is easily applied by ophthalmologists in the treatment of ocular surface diseases. This retrospective study included patients with ocular surface diseases who received ProKera^® between January 2022 and May 2023. Six patients (9 eyes) with a mean age of 56.8 ± 20.8 years old (range 25–74) and a mean follow-up period of 7.8 ± 4.1 months (range 1–12) were included, including 2 of recurrent conjunctival tumors with limbal and corneal involvement (cases 1–2), 1 of pterygium with marked astigmatism (case 3) and 3 of Stevens–Johnson syndrome (SJS, cases 4–6). ProKera^® was inserted after the lesion excision and deep keratectomy in cases 1–3, and no recurrence or corneal complication was noted. Cases 4–5 were discharged from the intensive care unit and presented with severe chronic SJS. Most ocular manifestations improved significantly after symblepharon release and ProKera^® insertion, except for corneal conjunctivalization in 1 eye (case 5). Case 6 involved early ProKera^® use at the bedside during acute SJS, resulting in complete resolution. We concluded that the adjunctive application of ProKera^® can be effective for ocular surface reconstruction and provides options to intervene earlier for outpatients or patients unstable for invasive surgical intervention.

Objectives: To unveil the candidate susceptibility genes in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy using whole exome sequencing (WES) and genome-wide association study (GWAS). Methods: Patients with a diagnosis of CQ/HCQ retinopathy based on the comprehensive demographic and ocular examination were included. The peripheral blood was extracted for WES and GWAS analyses. The Chinese Han Southern database from 1000 genomes was used as control group to compare the affected percentage. Multivariate logistic regression analysis adjusted for age, HCQ dose, duration and renal disease were used to analyze the correlation between genetic variants and visual outcome. A poor vision outcome was defined as visual acuity <6/12. An abnormal anatomical outcome was defined as disruption of ellipsoid zone in the fovea. Results: Twenty-nine patients with an average age of 60.9 ± 13.4 years, treatment duration of 12.1 ± 6.2 years, daily dose of 8.5 ± 4.1 mg/kg, and the cumulative dose of 1637.5 ± 772.5 g, were genotyped. Several candidate genes associated with CQ/HCQ retinopathy were found, including RP1L1, RPGR and RPE65, with a difference of affected percentage over 50% in mutation between the case and control groups. New foci in CCDC66: rs56616026 (OR = 63.43, p = 1.63 × 10⁻⁸) and rs56616023 (OR = 104.7, p = 5.02 × 10^-10) were identified significantly associated with HCQ retinopathy. Multivariate analysis revealed increased genetic variants were significantly associated with poor functional (OR = 1.600, p = 0.004) and structural outcome (OR = 1.318, p = 0.043). Conclusions: Several candidate susceptibility genes including RP1L1, RPGR, RPE65 and CCDC66 were identified to be associated with CQ/HCQ retinopathy. In addition to disease susceptibility, patients with increased genetic variants are more vulnerable to poor visual outcomes.

Aim: There remain limited therapies to treat thyroid eye disease (TED) orbital fibrosis, highlighting the urgency to develop novel targets. Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts are important pathogenetic factor of TED. Endoplasmic reticulum (ER) stress may play a role in TED pathogenesis since it has been linked to liver, kidney, heart and lung fibrotic remodelling. We would evaluate the role of thioredoxin domain containing 5 (TXNDC5), a fibroblast-enriched ER protein, in TGF-β1-induced myofibroblast transdifferentiation from TED orbital fibroblasts. Methods: Orbital fibroblasts from patients with TED were treated with TGF-β1 to investigate ER stress-relative gene expression especially for TXNDC5. To determine if TXNDC5 is involved in TGF-β1-induced fibrosis, we transfected TED orbital fibroblasts by lentivirus with a small hairpin RNA of pLKO-TXNDC5 gene (shTXNDC5) to knockdown TXNDC5 protein expression levels. After transfection of shTXNDC5 in TED orbital fibroblast followed by TGF-β1 treatment, we analysed TGF-β1-induced fibrosis protein expression. Results: We measured increased TXNDC5 gene and protein expression in primary TED orbital fibroblasts. TXNDC5 protein levels were increased in TED orbital fibroblasts under TGF-β1 stimulation (2.5, 5, 10 and 20 ng/mL). Moreover, TXNDC5 knockdown of attenuated TGFβ1 (5 ng/mL)-induced myofibroblast transdifferentiation and extracellular matrix protein upregulation whereas increasing TXNDC5 expression by a recombinant protein of TXNDC5 (rhTXNDC5) addition increased alpha smooth muscle actin, fibronectin and connective tissue growth factor protein expression. Conclusion: In conclusion, targeting TXNDC5 may be a novel therapeutic approach against TGF-β1-induced myofibroblast transdifferentiation in TED orbital fibroblasts.