tacrolimus and Keratoconjunctivitis-Sicca

Human T-cell lymphotropic virus (HTLV) is the first discovered retrovirus causing malignancy in human. HTLV infection affects host's ocular tolerance and causes various diseases in the eye. Here we discuss the manifestations, mechanisms, treatments, and future directions of HTLV-related ocular diseases. RECENT FININGS: Recent serological researches showed that the number of HTLV-1 carriers in metropolitan area was increasing, although seroprevalence of HTLV-1 in general population was decreased after screening serological tests in blood donors started. The most common clinical entity of uveitis was still HTLV-1 uveitis in HTLV-1 highly endemic area, but prevalence of HTLV-1 uveitis varies in different parts of the world. As for treatment of inflammation, tacrolimus and 5-azacytidine were reported to be effective for autoimmune manifestations in HTLV-1-related overlap syndrome (deratomyositis/Sjogren's syndrome) and HTLV-1-related myelodysplastic syndrome. Interleukin-2 receptor targeted therapies improved scleritis in patients with adult T-cell leukemia/lymphoma caused by HTLV-1. Basic researches identified that HTLV-1 tax and HTLV-1 basic leucine zipper factor play critical roles in the HTLV-1-related disease and are now being investigated as targeted therapies.. Development of modern molecular biology makes it possible to reveal deep insights of HTLV-1-related ocular diseases. Although effective therapies based on basic researches have been reported, further endeavor is necessary to establish much more specific treatments of the ocular diseases.

Topics: Azacitidine; Enzyme Inhibitors; Human T-lymphotropic virus 1; Humans; Immunosuppressive Agents; Keratoconjunctivitis Sicca; Leukemia-Lymphoma, Adult T-Cell; Tacrolimus; Uveitis

To assess the clinical safety and efficacy of adjunctive therapy using Vizoovet to ameliorate clinical signs of keratoconjunctivitis sicca (KCS) in dogs.. Twenty client-owned dogs.. Canine patients diagnosed with KCS were enrolled in this prospective study. Patients were randomly selected to receive either Vizoovet or GenTeal drops twice daily in addition to twice daily tacrolimus 0.03% solution. Data were collected from only one eye of each patient and included STT-1, IOP, TFBUT, and results of objective clinical scoring performed by pet owners. Statistical significance was set at P ≤ .05.. In all, 20 dogs (20 eyes) were enrolled in this prospective randomized study. Females (n = 12; 60%) outnumbered males (n = 8; 40%) and all dogs were spayed/neutered. Mean age of all dogs was 10.6 ± 3.79 years. In both treatment groups, the improvement in STT-1 values over the course of the study was significant (P = .002). When comparing the STT-1 improvements between groups, no significance was found (P = .78). In both groups, the improvement in TFBUT was significant (P = .0018). When comparing the TFBUT improvements between groups, no significance was found (P = .14). Squinting, rubbing, ocular discharge, and medication administration scores all significantly improved throughout the course of the study; however, they did not differ significantly between groups. Throughout the study, no adverse side effects were noted clinically or by the pet owner in either group.. Adjunctive treatment with Vizoovet was as safe and effective as GenTeal drops at improving clinical signs of dry eye in dogs.

Topics: Animals; Dog Diseases; Dogs; Drug Therapy, Combination; Female; Immunosuppressive Agents; Keratoconjunctivitis Sicca; Male; Ophthalmic Solutions; Pedigree; Pilot Projects; Prospective Studies; Tacrolimus; Treatment Outcome

To assess the efficacy of 0.1% oclacitinib as a single agent, and in combination with tacrolimus 0.01%, for the control of ophthalmic signs of keratoconjunctivitis sicca (KCS) in dogs.. Thirty-two dogs (57 eyes) diagnosed with idiopathic KCS were included. Inclusion criteria were Schirmer Tear Test 1 (STT-1) values <15 mm/min and concurrent clinical signs such as ocular hyperemia and discharge.. The animals were submitted to a randomized, open-label, 5-week study and divided into 3 treatment groups treated with the following ophthalmic solutions: (a) 0.1% oclacitinib, (b) 0.1% oclacitinib +0.01% tacrolimus, and (c) 0.01% tacrolimus. Eye drops were instilled twice daily (12-hour intervals). At each follow-up examination, STT-1, clinical signs, and potential drug side effects were assessed.. Oclacitinib did not significantly improve STT-1 values or clinical scores. Tacrolimus alone and in combination with oclacitinib increased mean STT-1 values by 11.84 ± 5.2 and 12.46 ± 5.3 mm/min, respectively (P = 0.0001). Clinical scores of ocular discharge and hyperemia also improved significantly in both groups receiving treatment with tacrolimus (P < 0.05). However, addition of oclacitinib to tacrolimus provided no additional improvement over tacrolimus alone.. Topical 0.1% oclacitinib twice daily is not effective in controlling the ocular signs of KCS in dogs. 0.01% tacrolimus increased STT-1 values significantly and could potentially be used as a treatment for mild-to-moderate cases of KCS. Synergism between drugs did not occur, and therefore the use of oclacitinib is not justified in cases of canine KCS.

Topics: Animals; Calcineurin Inhibitors; Dog Diseases; Dogs; Female; Janus Kinase 1; Keratoconjunctivitis Sicca; Male; Ophthalmic Solutions; Protein Kinase Inhibitors; Pyrimidines; Sulfonamides; Tacrolimus

The aim of this study was to evaluate the efficacy of tacrolimus eye drops in alleviating the clinical symptoms of canine keratoconjunctivitis sicca (KCS) and to compare this efficacy with that of cyclosporine. The clinical study was conducted on 40 dogs diagnosed with idiopathic KCS. The dogs were divided into two groups of 20 animals each. In Group I, 0.75% cyclosporine eye drops were administered three times a day, while in Group II 0.02% tacrolimus eye drops were given twice daily. In addition, each group was subdivided into three subgroups based on the results of Schirmer tear test I (STT I). Clinical and ophthalmologic examinations were performed prior to the treatment as well as after one and two months of therapy. The application of both tacrolimus and cyclosporine resulted in a significant reduction of neovascularisation after the first and second month of treatment (P < 0.05, P < 0.001); however, in moderate and advanced stages, the observed efficacy of tacrolimus was higher. Across all patients, a significant increase in STT I values was observed after both the first and second month of treatment with tacrolimus (P < 0.01), as well as after two months of treatment with cyclosporine (P < 0.05). In both groups, some patients were observed to exhibit inhibited development of pigmentation, but an analysis of particular clinical cases and statistical data revealed no statistically significant discrepancies in the course of the study. In cases of advanced canine KCS, the efficacy of tacrolimus may be higher than that of cyclosporine.

Topics: Administration, Topical; Animals; Cyclosporine; Dog Diseases; Dogs; Female; Immunosuppressive Agents; Keratoconjunctivitis Sicca; Male; Ophthalmic Solutions; Tacrolimus

The aim of this study was to evaluate the efficacy of pimecrolimus oil-based eye drops in alleviating the clinical signs of keratoconjunctivitis sicca (KCS) in dogs and to compare the efficacy with that of cyclosporine A (CsA) ointment. An open-label, multicenter study enrolling 44 dogs previously untreated with CsA was conducted. Dogs were randomly assigned to a treatment group and medicated twice daily for 8 weeks. After that time the mean increase (+/-SEM) in the Schirmer tear test was 9.2+/-1.6 mm/min in the pimecrolimus group and 5.8+/-1.1 mm/min in the CsA group (P=0.085). The improvement in clinical signs of inflammation in eyes treated with pimecrolimus was significantly greater than in eyes treated with CsA (P=0.02). The results show that 1% pimecrolimus oily eye drops are as safe as and more effective than CsA ointment in controlling KCS in dogs.

Topics: Administration, Topical; Animals; Cyclosporine; Dog Diseases; Dogs; Female; Immunosuppressive Agents; Keratoconjunctivitis Sicca; Male; Ophthalmic Solutions; Tacrolimus; Treatment Outcome

The purpose of this study was to assess the condition of cells in the conjunctiva and corneal epithelium prior to and during cyclosporine- or tacrolimusbased treatment of keratoconjunctivitis sicca (KCS). The study was performed on 40 dogs with KCS. The dogs were divided into two groups of 20 animals each. In Group I, 0.75% cyclosporine eye drops were administered three times a day, while in Group II 0.02% tacrolimus eye drops were administered twice daily. Additionally, each group was subdivided into three subgroups based on the results of the Schirmer I tear test (STT I). Evaluation of cellular metaplasia in the cornea and the palpebral and bulbar conjunctiva based on the Nelson-Adams scale was performed by impression cytology using Millipore round filters (Millipore VSWP 01300 DA) of 25 μm pore diameter applied to the studied area. Ophthalmological and cytological examinations were performed prior to the treatment as well as after one and two months of therapy. In both groups, a decrease in Nelson-Adams values was observed, corresponding to the increasing STT values [R

Topics: Administration, Topical; Animals; Conjunctiva; Cornea; Cyclosporine; Dog Diseases; Dogs; Female; Immunosuppressive Agents; Keratoconjunctivitis Sicca; Male; Metaplasia; Ophthalmic Solutions; Tacrolimus

Poor corneal penetration and short residence time on the ocular surface are two major bottlenecks for conventional ophthalmic formulations. To overcome the foregoing dilemmas, we prepared two novel formulations of pimecrolimus nanomicelles (PNM) with particle size of 37.85 ± 1.21 nm and thermosensitive hydrogel (PTH) for treating Keratoconjunctivitis Sicca (KCS). PNM were investigated by transmission electron microscopy (TEM), Malvern laser particle size analyzer, X-ray diffraction (XRD) system, and the content of drug in PNM was measured by high-performance liquid chromatography (HPLC). The drug loading and encapsulation efficiency reached to 7.57% ± 0.10% and 97.9% ± 1.26%, respectively. PTH displayed special gel-sol transition behavior with temperature increasing from 4 °C to 37 °C. The in vitro release profile demonstrated that PNM and PTH exhibited sustained-release behavior compared with free pimecrolimus oil-based eye drop (FPO). In addition, we established a mouse model of KCS induced by benzalkonium chloride to evaluate the therapeutic outcome of different pimecrolimus formulations. The production of tear, fluorescein staining scores and histopathologic examinations of the cornea were assessed in detail. The results confirmed that PNM had the best therapeutic effect among all formulations based on its higher drug encapsulation capability, favourable permeability and sustained release. All these indicated that PNM could serve as a potent ophthalmologic agent for KCS.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid; Drug Liberation; Keratoconjunctivitis Sicca; Mice; Micelles; Microscopy, Electron, Transmission; Nanoparticles; Particle Size; Phase Transition; Tacrolimus; Transition Temperature; X-Ray Diffraction