Impact of ibrutinib on inflammation in a mouse model of Graves' orbitopathy.

Introduction: Bruton's tyrosine kinase (BTK) and interleukin (IL)-2 Inducible T-cell Kinase (ITK) inhibitors have anti-inflammatory properties. We investigated the therapeutic effect of ibrutinib, an orally bioavailable BTK/ITK inhibitor, in a mouse model of Graves' orbitopathy (GO). Methods: Genetic immunization was performed through intramuscular administration of the recombinant plasmid, pCMV6-hTSHR cDNA, to 8-week-old female BALB/c mice. Serum levels of T3, T4, and thyroid-stimulating hormone receptor (TSHR) antibodies (TRAbs) were quantified using enzyme-linked immunosorbent assay. Histopathological changes in orbital tissues were examined using immunohistochemistry (IHC) staining for TSHR and various inflammatory markers. Following successful genetic immunization, ibrutinib was orally administered daily for 2 weeks in the GO model mice. After treatment, the mRNA and protein expression levels of BTK, ITK, IL-1ß, and IL-6 in orbital tissues were evaluated using real-time PCR and Western blotting. Results: In total, 20 mice were sacrificed to confirm successful genetic immunization. The GO mouse group exhibited significantly increased serum T3, T4, and TRAb levels. IHC revealed increased expression of TSHR, IL-1ß, IL-6, transforming growth factor-ß1, interferon-γ, CD40, CD4, BTK, and ITK in the GO mouse model. The orbital inflammation was significantly attenuated in ibrutinib-treated mice. The mRNA and protein expression levels of BTK, ITK, IL-1ß, and IL-6 in orbital tissue were lower in ibrutinib-treated GO mouse group compared to the phosphate-buffered saline-treated GO mouse group. Conclusion: The GO mouse model demonstrated enhanced BTK and ITK expression. Ibrutinib, a BTK/ITK inhibitor, suppressed the inflammatory cytokine production. These findings highlight the potential involvement of BTK/ITK in the inflammatory pathogenesis of GO, suggesting its role as a novel therapeutic target.

Improvement of photovoltaic properties by addition of a perylene compound in P3HT:PCBM BHJ system.

The synthesized n-type perylene derivative, N,N'-bis-(4-bromophenyl)-1,6,7,12-tetrakis(4-n-butoxy-phenoxy)-3,4,9,10-perylene tetracarboxdiimide (PIBr), was applied as an additive to polymer solar cells (PSCs) with P3HT [poly(3-hexylthiophene)]:PCBM [[6,6]-phenyl C61-butyric acid methyl ester] blend films. Without post thermal annealing, a considerable improvement of about 98% in power conversion efficiency was achieved by the addition of 1 wt% PIBr into a P3HT:PCBM layer, when compared with that of reference cell without the additive. The results, in combination with relevant data from UV-Vis. absorption, photoluminescence, X-ray measurements and carrier mobility studies, revealed that the addition of the perylene compound within active layer contributed to more effective charge transfer and enhanced electron mobility.

Clinical Outcomes of Cataract Surgery in Patients with Sjögren's Syndrome.

This study compared the biometric accuracy and refractive outcomes, and ocular surface changes after cataract surgery in patients with Sjögren's syndrome (SS, S group), non-SS dry eye patients (D group), and healthy controls (C group). The medical records of patients who underwent cataract surgery and met certain inclusion criteria were reviewed. In total, 167 eyes of 87 patients were enrolled. Refractive parameters were analyzed via optical biometry and combined ultrasound biometry and automated refractokeratometry. The mean absolute errors (MAEs), the uncorrected distance visual acuities (UDVAs), changes in the ocular staining score (OSS), and anterior chamber cell grades were compared for 12 months postoperatively. The S group evidenced more severe and persistent OSS exacerbation after cataract surgery; the OSS returned to baseline by 3 months postoperatively. The mean keratometric values showed a significant linear correlation. There was no significant intergroup difference in either the MAEs (p > 0.530) or anterior chamber inflammation (p > 0.436). The postoperative UDVA of the S group was poorer than that of the C group from 3 months postoperatively (p < 0.047) but not different from that of the D group (p > 0.311). With preoperative ocular surface optimization and optimal postoperative treatment of superficial keratitis, the refractive outcomes of SS patients were comparable to those of other groups and the postoperative UDVA was not inferior to that of non-SS dry eye patients.

Update on the surgical management of Graves' orbitopathy.

Graves' orbitopathy (GO) is a complex autoimmune disorder of the orbit that causes the eye to appear disfigured. GO is typically associated with Graves' disease, an inflammatory autoimmune condition that is caused by thyrotropin receptor autoantibodies. Although our knowledge of the pathophysiology of GO has improved, its exact pathogenesis remains unclear. Some patients suffer from disfigurement, double vision, and even vision loss rather than hyperthyroidism. The disease severity and activity prompt different treatments, as the signs of GO are heterogeneous, so their management can be very complex. Despite medical advances, the first-line treatment for moderate-to-severe active GO is still glucocorticoids, while surgery can be critical for the treatment of chronic inactive GO. Surgery is sometimes required in the acute phase of the disease when there is an immediate risk to vision, such as in dysthyroid optic neuropathy. Most surgeries for GO are rehabilitative and subdivided into three categories: decompression, strabismus repair, and lid surgery. This review is a basic overview of the field, with up-to-date knowledge of the surgical techniques for GO. We review and summarize recent literature on the advances in surgery for GO to provide up-to-date insights on the optimal surgical treatment for GO.

MicroRNA-155 acts as an anti-inflammatory factor in orbital fibroblasts from Graves' orbitopathy by repressing interleukin-2-inducible T-cell kinase.

To investigate the role of microRNA (miR)-155 in inflammation in an in-vitro model of Graves' orbitopathy (GO). The expression levels of miR-155 were compared between GO and non-GO orbital tissues. The effects of inflammatory stimulation of interleukin (IL)-1ß and tumour necrosis factor alpha (TNF-α) on miR-155 expression on GO and non-GO orbital fibroblasts (OFs) were investigated. The effects of miR-155 mimics and inhibitors of inflammatory proteins and IL-2-inducible T-cell kinase (ITK) expression were examined, along with those related to the knockdown of ITK with siITK transfection on inflammatory proteins. We also examined how ITK inhibitors affect miR-155 expression in GO and non-GO OFs. The expression levels of miR-155 were higher in GO orbital tissues than in non-GO tissue. The overexpression of miR-155 was induced by IL-1ß and TNF-α in OFs from GO and non-GO patients. IL-1ß-induced IL-6 (ICAM1) protein production was significantly reduced (increased) by miR-155 mimics and inhibitors. The mRNA and protein levels of ITK were downregulated by overexpressed miR-155 via miR-155 mimics. Knockdown of ITK via siITK transfection induced a decrease in the expression levels of ITK, IL-17, IL-6, IL-1ß, and TNF-α protein. The expression of miR-155 was significantly downregulated by treatment with ITK inhibitors and Bruton's tyrosine kinase (BTK)/ITK dual inhibitors in a time-dependent manner. Our results indicated a potential relationship between miR-155 and ITK in the context of GO OFs. The overexpression of miR-155 repressed ITK expression and relieved inflammation. Thus, miR-155 appears to have anti-inflammatory effects in GO OFs. This discovery provides a new concept for developing GO treatment therapeutics.

Combined Vitrectomy With Macular Buckling In High Myopic Eyes With Macular Hole Retinal Detachment: A Pilot Study Of A Novel Snail-Tipped Exoplant.

PURPOSE: To evaluate the efficacy of a novel snail-tipped exoplant for macular buckling combined with vitrectomy in high myopic eyes with macular hole retinal detachment. PATIENT AND METHODS: A novel exoplant was simply prepared with a 5 × 3 mm silicone sponge strengthened in the center with a malleable titanium plate. One end was bent to make a rolled tip like a snail shell to be placed under the macula. Combined vitrectomy with macular buckling using this exoplant was performed in eight consecutive cases. The long arm of the exoplant was manipulated manually to fit the curvature of the eyeball and the length was trimmed appropriately after scleral suturing of the exoplant. RESULTS: Retinal reattachment was achieved in all cases (100%) and macular hole closure was confirmed in 6 eyes (75%). The mean best-corrected visual acuity improved from 1.53 ± 0.73 LogMAR preoperatively to 1.14 ± 0.59 LogMAR to postoperatively (p = 0.063). The mean pre- and postoperative AL was 28.44 ± 1.86 mm and 27.60 ± 1.83 mm, respectively (p = 0.016). The mean follow-up period was 15.4 months and no buckle-related complications such as diplopia, infection or exposure of the exoplant were noticed during the period. CONCLUSION: This exoplant could easily be prepared with readily available materials in the operating room and it was well tolerated with favorable anatomic results in high myopic eyes. Further studies of increased number of patients with long-term follow-up will be necessary.