tacrolimus and Conjunctival-Diseases

To evaluate the safety and efficacy of topical tacrolimus 0.05% versus topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD).. Phase 1/2 prospective, randomized, double-masked clinical trial.. Eighty eyes of 40 patients diagnosed with chronic ocular GVHD were enrolled.. Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients were treated with topical methylprednisolone 0.5% twice daily for 10 weeks, in addition to continuing their baseline treatment regimen.. Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subject reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy end points were corneal fluorescein staining (CFS), tear film break-up time (TBUT), Schirmer test results, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI).. After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the 2 groups (P = 0.06). However, burning sensation was more pronounced with tacrolimus (P = 0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P = 0.01) and achieved significant improvement in TBUT when compared with baseline (P < 0.001). Reduction in OSDI score achieved statistical significance with tacrolimus (27% reduction; P = 0.02), but was marginal with methylprednisolone (32% reduction; P = 0.06). Expression of ICAM-1 by ocular surface epithelium decreased significantly in both groups (tacrolimus, P = 0.003; methylprednisolone, P = 0.008), whereas HLA-DR expression decreased significantly only in the tacrolimus group (P = 0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P = 0.04).. Topical tacrolimus 0.05% is safe, generally well tolerated, and effective for the treatment of ocular GVHD without the hypertensive effects of topical corticosteroids.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Conjunctival Diseases; Corneal Diseases; Double-Blind Method; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Methylprednisolone; Middle Aged; Prospective Studies; Tacrolimus

Ocular graft-versus-host disease (GVHD) is one of the most severe complications of hematopoietic stem cell transplantation. It manifests as an impairment of the ocular surface, such as severe dry eye disease, and deteriorates the recipient's visual function and quality of life. We encountered an "overlap syndrome" of ocular GVHD, which is characterized by the presence of both acute and chronic GVHD symptoms. In this report, we present the treatment progress of the overlap syndrome in a case with ocular GVHD.. A 57-year-old man with acute myeloblastic leukemia underwent hematopoietic stem cell transplantation. Six weeks after the treatment, the recipient complained of eye pain and discharge. He was diagnosed with the overlap syndrome due to low tear volume, severe corneal epithelitis, hyperemia, and a pseudomembrane on the conjunctiva. Immune cells infiltration, fibrinoid degeneration, fibroblastic and spindle-shaped cells, and fibrosis were observed in the pathology of the pseudomembrane. The recipient was treated with topical immunosuppression and pseudomembrane removal. One week after the initial treatment, ocular GVHD improved. Twelve weeks after the treatment, the topical steroid was discontinued due to the elevation of intraocular pressure.. The assessment of conjunctival pseudomembrane in ocular GVHD is important to determine the stage of the case and to assess systemic GVHD. Furthermore, prompt removal of the pseudomembrane after diagnosis is an appropriate management to reduce the symptoms of ocular GVHD. The combination of topical steroids and immunosuppressive agents is suggested to be an effective treatment in management of overlap syndrome.

Topics: Acute Disease; Betamethasone; Chronic Disease; Conjunctival Diseases; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Intestinal Diseases; Leukemia, Myeloid, Acute; Male; Middle Aged; Ophthalmologic Surgical Procedures; Skin Diseases; Tacrolimus

To find safer and more effective drugs than mitomycin C to prevent conjunctival fibrosis in a rabbit model.. Twenty-four rabbits were involved and randomly divided into four groups. Limbus-based peritomy was performed at the superior cornea, and normal saline (NS group), mitomycin C (MMC group), SR (SR group), or TC (TC group)-coated silicone plate was inserted at the sub-Tenon's space in each group. Conjunctival congestion was evaluated at 1 and 4 weeks postoperatively. At 4 weeks, the numbers of inflammatory cells, fibroblasts, myofibroblasts, blood vessels, and goblet cells were counted in the conjunctiva and Tenon's capsule around the silicone plate.. At 4 weeks, conjunctival congestion was significantly less than that observed at 1 week in the SR and TC groups (p < 0.05), whereas the number of myofibroblasts was significantly lower in the MMC and TC groups (p < 0.05). The conjunctiva was significantly less congested in the TC group versus the other groups at 1 week and 4 weeks (p < 0.05). The TC group had the lowest number of inflammatory cells and MMC group had the lowest number of goblet cells among all groups (p < 0.05).. The TC-coated silicone plate was more effective in inhibiting inflammation and fibrosis versus the MMC-coated silicone plate and was associated with fewer adverse effects in the rabbit model.

Topics: Animals; Conjunctiva; Conjunctival Diseases; Cornea; Disease Models, Animal; Fibroblasts; Fibrosis; Goblet Cells; Male; Mitomycin; Rabbits; Silicones; Tacrolimus; Tenon Capsule

Topics: Aged; Antithrombins; Atrial Fibrillation; Conjunctival Diseases; Dabigatran; Drug Interactions; Drug Substitution; Eye Hemorrhage; Female; Humans; Immunosuppressive Agents; International Normalized Ratio; Liver Transplantation; Renal Insufficiency; Tacrolimus; Treatment Outcome

The purposes of this study were to investigate the effects of topically administrated Tacrolimus and Octreotide on modulation of postoperative scarring in experimental glaucoma filtration surgery and to compare the antifibrotic properties of these agents with mitomycin-C (MMC).. A total of 28 New Zealand rabbits weighing 2.5-3 kg were randomly divided into a surgical control (SC) group and three experimental groups. Standard filtration surgeries were performed on the right eyes of all the rabbits. The rabbits in the SC group received only vehicle after the surgeries, whereas the rabbits in the three experimental groups were treated either with 0.4 mg/mL MMC during the surgery (MMC group) or with 0.3 mg/mL Tacrolimus drop four times a day (TT group) or with 10 µg/mL Octreotide drop three times a day (OT group) for 14 days. The animals were killed on day 14, eyes were enucleated and histologically and immunohistochemically analyzed.. In SC group mean fibroblast, mononuclear cell number and fibroblast growth factor-β (FGF-β), transforming growth factor-β (TGF-β) immunostaining intensity was higher than all treatment groups. In OT group mean fibroblast number was lesser than MMC (p < 0.01) and TT (p < 0.05) group. In TT group mean fibroblast number was lesser than MMC group (p < 0.05). Mean mononuclear cell number was similar between MMC, OT and TT groups (p > 0.05). In MMC, OT and TT groups mean TGF-β and FGF-β immunostaining intensity was similar (p > 0.05).. Topically administration of Tacrolimus and Octreotide effectively reduced the subconjuntival scarring response 2 weeks after experimental glaucoma filtration surgery.

Topics: Administration, Topical; Alkylating Agents; Animals; Cicatrix; Conjunctival Diseases; Disease Models, Animal; Fibroblast Growth Factor 2; Fibroblasts; Fibrosis; Filtering Surgery; Glaucoma; Immunoenzyme Techniques; Immunosuppressive Agents; Leukocyte Count; Mitomycin; Octreotide; Ophthalmic Solutions; Postoperative Complications; Rabbits; Tacrolimus; Transforming Growth Factor beta