tacrolimus and Glaucoma

To report outcomes of tacrolimus immunosuppression after penetrating keratoplasty (PK) in very young children.. Retrospective, consecutive, cohort study of children undergoing PK at a tertiary children's hospital between 2005 and 2016. Oral tacrolimus immunosuppression was given for 2 years, followed by topical tacrolimus.. Fourteen children (20 eyes) had 24 PKs; nineteen eyes had primary PKs, five eyes had repeat PKs. Mean age at primary graft was 95 days (3.1 months) for anterior segment dysgenesis (ASD), 430 days (14.3 months) for non-ASD children. Eleven children (15 eyes) had ASD. Three children (five eyes) had non-ASD: two children (three eyes) had glaucoma-related corneal opacity and one child (two eyes) had congenital hereditary endothelial dystrophy (CHED). One-year rejection-free survival rates following primary PK was 80% for ASD (n = 15) and 100% for non-ASD (n = 4). At final review, 5/15 of primary grafts for ASD were clear. 10/15 failed after a mean of 19 months, specifically attributable to infection (n = 2), rejection (n = 2) and glaucoma (n = 2). 4/4 primary non-ASD grafts are clear at final review (mean follow-up = 77 months). All repeat grafts (n = 5), failed after a mean of 38.25 months. Considering all grafts, 15/24 (62.5%) failed: 5/15 due to infection, 2/15 due to rejection, 8/15 due to glaucoma, phthisis, perforation or vascularised with no rejection. At last review (mean = 58.1 months, range 28-84), overall cohort survival is 37.5%. Final visual acuities range between 0.86 and 2.4 LogMAR.. We compare our results to published literature: 1-year graft survival was higher than previously reported, with lower failure due to rejection. Overall infection rates did not increase, however, proportionally, severe infections were higher. Overall graft survival is at least comparable to reported literature.

Topics: Child; Child, Preschool; Cohort Studies; Follow-Up Studies; Glaucoma; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Infant; Infant, Newborn; Keratoplasty, Penetrating; Retrospective Studies; Tacrolimus

To determine whether topical tacrolimus can lessen steroid-induced intraocular pressure (IOP) elevation.. Open cohort post hoc analysis study.. Five hundred eleven patients with vernal keratoconjunctivitis or atopic keratoconjunctivitis (mean age 17.0 ± 9.2 years) were studied. All 511 patients were treated with topical tacrolimus with or without topical steroids, and the changes in IOP were measured monthly for 3 months. The elevation in IOP induced by use of topical steroids was calculated using mixed linear regression analyses. The relationship between the elevation in IOP within 4 weeks and the use or nonuse of tacrolimus reported in published data was analyzed using metaregression analysis to estimate the effects of tacrolimus on the IOP in eyes treated with topical steroids.. The mean topical steroid-induced IOP elevation in tacrolimus-treated eyes was lower, by 5.2 mmHg (P = 0.04), than that in earlier published data without tacrolimus as the control. In the tacrolimus-treated eyes, the mean betamethasone-induced IOP elevation was 1.3 mmHg without discontinuation of the steroid. Metaregression analysis indicated that glaucoma history and younger age had significant effects on topical steroid-induced IOP elevation, by 4.0 mmHg (P = 0.002) and 3.9 mmHg (P = 0.01), respectively. In tacrolimus-treated eyes, the most significant effect on the IOP was associated with glaucoma history or medication; however, its effect on the IOP was limited to 1.7 mmHg elevation (P = 0.006).. Topical tacrolimus may lessen the steroid-induced elevation in IOP in younger individuals and may be a good adjunctive therapy to avoid IOP elevation in refractory cases.

Topics: Adolescent; Betamethasone; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Tacrolimus; Tonometry, Ocular

To investigate the effect of tacrolimus on the proliferation of fibroblasts after glaucoma surgery.. Biopsy was applied in this study. Under aseptic conditions, tissues were collected from rabbits, cut into small pieces and cultured. Morphology of fibroblasts was observed under a microscope. Features of fibroblasts were identified via immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Western blotting and RT-PCR were performed to detect the expressions of related proteins after treatment. Flow cytometry and cell counting kit-8 (CCK-8) assay were employed to examine the proliferation of human Tenon's capsule fibroblasts (HTFs) after tacrolimus treatment.. Tacrolimus decreased the levels of survivin and α-smooth muscle actin (α-SMA) after transforming growth factor-β (TGF-β) treatment. Besides, it inhibited proliferation and induced apoptosis of HTFs.. Tacrolimus reduces proliferation and promotes apoptosis of HTFs by inhibiting the expression of survivin, which may be a strategy for treating hypertrophic scar after glaucoma surgery.

Topics: Actins; Animals; Apoptosis; Cell Proliferation; Cells, Cultured; Cicatrix; Fibroblasts; Glaucoma; Humans; In Vitro Techniques; Rabbits; Survivin; Tacrolimus; Tenon Capsule; Transforming Growth Factor beta

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

The purpose of this study was to investigate ocular complications among a group of patients on long-term, high-dose immunosuppression and corticosteroids for the maintenance of orthotopic heart transplants. Additionally, we provided information pertinent for the early diagnosis and treatment of eye diseases. In this study, we retrospectively assessed the clinical data of 138 patients with orthotopic heart transplantations from May 2000 to October 2005, including assessment of ophthalmic symptoms and signs, as well as the general condition, treatment, and prognosis. Of 138 transplant recipients examined (276 eyes), 47 eyes (17.0%) showed ocular surface diseases. Sixty-four (23.2%) had a posterior subcapsular cataract, and 16 (5.8%) corticosteroid glaucoma. Fifteen (5.6%) had ocular fundus diseases. Various ocular complications related to immunosuppression and corticosteroids appear among heart transplant patients. Cardiac surgeons and ophthalmologists must closely evaluate ocular symptoms in the posttransplantation period.

Topics: Asian People; Cataract; China; Eye Diseases; Female; Follow-Up Studies; Glaucoma; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Retrospective Studies; Tacrolimus

To evaluate the long-term efficacy and side effects of off-label topical tacrolimus 0.03% ointment (Protopic; Fujisawa Health, Deerfield, IL) as a sole second-line immunosuppressive agent in the management of high-risk corneal grafts.. Four consecutive patients underwent high-risk penetrating keratoplasty (4 grafts) with a prior diagnosis of corneal scar secondary to herpetic keratitis, keratoconus, acanthamoeba keratitis, and Fuchs endothelial dystrophy, respectively. All 4 patients developed steroid-induced glaucoma and failed traditional immunosuppressant therapy. Patients were started on topical tacrolimus ointment 0.03%, twice daily, which was tapered to the lowest possible therapeutic dose that maintained its antirejection efficacy. Patients were monitored for adverse treatment effects. The mean follow-up was 33 months (range, 26-48 months), and the mean treatment duration was 22.6 months (range, 13-32 months).. All 4 high-risk corneal transplant patients experienced episodes of acute rejection that was successfully reversed with topical tacrolimus treatment. During tacrolimus treatment, there were no further episodes of graft rejection and no incidents of herpes simplex virus infection or reactivation, with the longest follow-up being 4 years. Two patients have been successfully tapered off tacrolimus, and 2 patients are currently on once-daily dosing. No adverse effects were observed.. Topical tacrolimus 0.03% ointment seems to be a promising second-line immunosuppressant in management of high-risk grafts.

Topics: Administration, Topical; Female; Follow-Up Studies; Glaucoma; Glucocorticoids; Graft Rejection; Humans; Immunosuppressive Agents; Keratoplasty, Penetrating; Male; Middle Aged; Ointments; Retrospective Studies; Risk Factors; Tacrolimus; Treatment Outcome

Increased intraocular pressure (IOP) leads, by an unknown mechanism, to apoptotic retinal ganglion cell (RGC) death in glaucoma. We now report cleavage of the autoinhibitory domain of the protein phosphatase calcineurin (CaN) in two rodent models of increased IOP. Cleaved CaN was not detected in rat or mouse eyes with normal IOP. In in vitro systems, this constitutively active cleaved form of CaN has been reported to lead to apoptosis via dephosphorylation of the proapoptotic Bcl-2 family member, Bad. In a rat model of glaucoma, we similarly detect increased Bad dephosphorylation, increased cytoplasmic cytochrome c (cyt c), and RGC death. Oral treatment of rats with increased IOP with the CaN inhibitor FK506 led to a reduction in Bad dephosphorylation and cyt c release. In accord with these biochemical results, we observed a marked increase in both RGC survival and optic nerve preservation. These data are consistent with a CaN-mediated mechanism of increased IOP toxicity. CaN cleavage was not observed at any time after optic nerve crush, suggesting that axon damage alone is insufficient to trigger cleavage. These findings implicate this mechanism of CaN activation in a chronic neurodegenerative disease. These data demonstrate that increased IOP leads to the initiation of a CaN-mediated mitochondrial apoptotic pathway in glaucoma and support neuroprotective strategies for this blinding disease.

Topics: Analysis of Variance; Animals; Apoptosis; bcl-Associated Death Protein; Blotting, Western; Calcineurin; Calcineurin Inhibitors; Cytochromes c; Female; Glaucoma; Intraocular Pressure; Male; Mice; Mice, Inbred DBA; Mitochondria; Optic Nerve; Phosphorylation; Rats; Rats, Inbred BN; Retinal Ganglion Cells; Tacrolimus