The Role of Fibrogenesis and Extracellular Matrix Proteins in the Pathogenesis of Graves' Ophthalmopathy.

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.

Role of BMI and age in predicting pathologic vertebral fractures in newly diagnosed multiple myeloma patients: A retrospective cohort study.

Vertebral fractures affect approximately 30% of myeloma patients and lead to a poor impact on survival and life quality. In general, age and body mass index (BMI) are reported to have an important role in vertebral fractures. However, the triangle relationship among age, BMI, and vertebral fractures is still unclear in newly diagnosed multiple myeloma (NDMM) patients. This study recruited consecutive 394 patients with NDMM at Taipei Veterans General Hospital between January 1, 2005 and December 31, 2015. Risk factors for vertebral fractures in NDMM patients were collected and analyzed. The survival curves were demonstrated using Kaplan-Meier estimate. In total, 301 (76.4%) NDMM patients were enrolled in the cohort. In the median follow-up period of 18.0 months, the median survival duration in those with vertebral fractures ≥ 2 was shorter than those with vertebral fracture < 2 (59.3 vs 28.6 months; P = 0.017). In multivariate Poisson regression, BMI < 18.5 kg/m2 declared increased vertebral fractures compared with BMI ≥ 24.0 kg/m2 (adjusted RR, 2.79; 95% CI, 1.44-5.43). In multivariable logistic regression, BMI < 18.5 kg/m2 was an independent risk factor for vertebral fractures ≥ 2 compared with BMI ≥ 24.0 kg/m2 (adjusted OR, 6.05; 95% CI, 2.43-15.08). Among age stratifications, patients with both old age and low BMI were at a greater risk suffering from increased vertebral fractures, especially in patients > 75 years and BMI < 18.5 kg/m2 (adjusted RR, 12.22; 95% CI, 3.02-49.40). This is the first study that demonstrated that age had a significant impact on vertebral fractures in NDMM patients with low BMI. Elder patients with low BMI should consider to routinely receive spinal radiographic examinations and regular follow-up.

Risk Factors for Developing Neovascular Glaucoma in Central Retinal Vein Occlusion: Two-Year Real-World Study.

PURPOSE: To explore potential risk factors for the development of neovascular glaucoma (NVG) in central retinal vein occlusion (CRVO) over a two-year intensive follow-up period. METHODS: This study reviewed 1545 patients with CRVO between 2005 and 2019 at Taipei Veterans General Hospital. Inclusion was restricted to (1) patients with acute CRVO within 3 months; (2) patients with ocular neovascularization at initial presentation (3) patients had not received any treatment at the time of CRVO; (4) at least bimonthly follow-up schedule over the course of 2 years. The included patients were screened for potential risk factors for developing NVG and assessed with Kaplan-Meier survival analysis and Cox regression model. RESULTS: Among the included 123 patients, the cumulative probability of developing NVG was 26.8% (33/123 cases) in overall follow-up period. The mean interval between the onset of CRVO and NVG was 507 days. Neither macular edema nor central macular thickness at baseline was correlated with the development of NVG (p =.104 and .25, respectively). Patients with diabetes mellitus (DM), older age, and poor vision independently played significant risk factors for developing NVG after controlling other covariates. (p =.034, .001, and .013, respectively). CONCLUSIONS: Patients presenting with CRVO who have comorbidities such as DM, older age, and worse VA warrant closer attention and intensive follow-up for the development of NVG. Additionally, the statistical analysis indicated that the presence of macular edema, increased central macular thickness, CV events, history of glaucoma, and early PRP within 3 months had no significant impact on the likelihood of developing NVG.

Exome sequencing and genome-wide association analyses unveils the genetic predisposition in hydroxychloroquine retinopathy.

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.

Self-Retained, Sutureless Amniotic Membrane Transplantation for the Management of Ocular Surface Diseases.

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.

Outcomes and risk factors for failure after trabeculectomy in Taiwanese patients: medical chart reviews from 2006 to 2017.

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 (p<0.001) and 3.0±0.7 to 1.8±1.2 (p=0.015), respectively, at the last visit. Cumulative qualified success rates were 93.9%, 93.0%, 86.5% and 67.1% at the 1, 2, 5 and 10 years follow-up, respectively; however, only 7.7% of the eyes reached complete success at the last visit. Eyes with poor preoperative visual acuity were associated with low qualified success rates (HR=1.689, p=0.027); patients aged >70 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.

Temporal fluctuations of cardiovascular parameters after intravitreal injections.

BACKGROUND: Despite the effectiveness of intravitreal injection (IVI) of anti-vascular endothelial growth factor in treating retinal diseases, there remains a paucity of evidence on potential systemic risks associated with this procedure. This study aims to investigate cardiovascular parameters and the risk of hypertensive urgency after IVIs. METHODS: Patients who received IVIs for retinal/macular diseases were enrolled retrospectively. Patients who received cataract surgeries were enrolled as controls. Systolic and diastolic blood pressure (BP) and heart rate were measured 10 minutes before, immediately after, and more than 30 minutes after IVIs and cataract surgery. Multivariate analysis was performed to evaluate risk factors for hypertensive urgency. RESULTS: Seventy patients who received IVIs and 95 patients who received cataract surgeries were enrolled. A higher preoperative systolic BP was found in the IVI groups than in the control group (147.0 ± 22.9 vs 136.3 ± 21.8 mmHg, respectively). The patients who received IVIs had a higher increase in perioperative systolic BP immediately after the procedure than the controls (17.43 ± 20.53 mmHg vs 9.11 ± 18.92 mmHg, p = 0.009). The IVI procedure (odds ratio [OR] 4.84, p = 0.008), preoperative systolic BP ≥160 mmHg (OR 17.891, p = 0.001, compared to preoperative systolic BP <140 mmHg), and underlying hypertension (OR 3.305, p = 0.041) were risk factors for hypertensive urgency immediately after the IVIs. CONCLUSION: We found a transient increase in BP after IVIs, which may have been associated with hypertensive urgency and related cardiovascular disorders in older patients and in those with relevant comorbidities. Clinicians should pay more attention to these patients before performing IVIs.