tacrolimus and Dry-Eye-Syndromes

To compare the effect of topical application of tacrolimus 0.03% eyedrops versus cyclosporine 0.05% in Sjogren syndrome subjects with severe dry eyes.. A prospective single-blinded simply randomized controlled study.. 60 Sjogren patients were randomized intoGroup A: 30 patients were instructed to put tacrolimus 0.03% eyedrops in one eye for 6 months and placebo eyedrops in the other eye, (. Upon comparing both eyedrops, the mean value of OSDI decrease was 38.25 ± 18.29% versus 31.69 ± 18.57% (. Both tacrolimus and cyclosporine significantly improved patient symptoms, frequency of artificial tears use and ocular surface staining compared to placebo-controlled eyes. However, no significant difference regarding the efficacy of both eyedrops at the end of 6 months treatment of severe dry eyes of Sjögren syndrome patients.. ClinicalTrials.gov. Identifier: NCT03865888.

Topics: Cyclosporine; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Ophthalmic Solutions; Prospective Studies; Sjogren's Syndrome; Tacrolimus; Tears

To describe the clinical efficacy of the treatment of Sjögren's syndrome dry eye using 0.03% tacrolimus eye drop.. Prospective double-blind randomized study.. Institutional outpatient clinic.. Forty-eight eyes of twenty-four patients with dry eye related to Sjögren syndrome were enrolled in this study. The patients were randomized in 2 groups: tacrolimus (n=14) and vehicle (n=10) group.. The tacrolimus group received a vial containing tacrolimus 0.03% (almond oil as vehicle) and the other group received the almond oil vehicle. All patients were instructed to use the eye drops every 12h in the lower conjunctival sac.. Schirmer I test, break-up-time (BUT), corneal fluorescein and Rose Bengal staining scores were evaluated in all patients one day before the treatment (baseline), 7, 14, 28 and 90 days after treatment with the eye drops.. The average fluorescein and Rose Bengal scores improved statistically after 7 days of treatment and even more after 90 days. The average Schirmer I and BUT values were unchanged after 7, 14 and 21 days but did show an improvement relative to baseline after 28 days of treatment. Schirmer I, BUT, fluorescein and Rose Bengal did not show any statistical significance in the vehicle group.. Topical 0.03% tacrolimus eye drop improved tear stability and ocular surface status in cases of inflammatory or SS-related dry eye.. ClinicalTrials.gov Identifier: NCT01850979.

Topics: Administration, Ophthalmic; Double-Blind Method; Dry Eye Syndromes; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Sjogren's Syndrome; Tacrolimus; Tears; Treatment Outcome

The off-label use of topical tacrolimus (Protopic) for inflammatory external eye diseases is gaining popularity. However, there are no reports on the safety profile of this new treatment option.. We treated six patients with different inflammatory eye diseases with topical tacrolimus (Protopic 0.03 %) as off-label use in addition to the conventional anti-inflammatory treatment. Patients were interviewed for side effects and serum drug concentrations were measured under steady state conditions one hour after topical application of tacrolimus ointment.. Two patients reported a slight burning sensation immediately after application, in one patient we found a slight worsening of the dry eye problems. No patient abandoned the treatment due to side effects. Serum drug concentrations remained below the analytical threshold in all cases (< 1.5 ng/ml).. Tacrolimus for the topical treatment of anterior segment inflammatory eye diseases is well tolerated without detectable systemic drug resorption.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dry Eye Syndromes; Humans; Immunosuppressive Agents; Keratitis; Middle Aged; Tacrolimus; Young Adult

Topics: Dry Eye Syndromes; Hair Diseases; Humans; Patients; Sjogren's Syndrome; Tacrolimus

The present work aimed to evaluate the efficacy of topical tacrolimus (0.01%) loaded propylene glycol (PG) modified nano-vesicles (Proglycosomes Nano-vesicles, PNVs) for the treatment of experimental dry eye syndrome (DES) in rabbits. DES was induced by topical application of atropine (1.0%) and benzalkonium chloride (0.1%) aqueous solution. PNVs treatment (PNV group) was compared with tacrolimus solution 0.01% (TAC group) and untreated group and healthy group were used as controls. PNV treated animals showed improved clinical performance with marked increase in tear production and tear break-up time (TBUT). Further, PNVs also subside ocular inflammation as evident from absence of matrix metalloprotenaise-9 and normal ocular surface temperature (32.3 ± 0.34 °C). Additionally, PNVs have positive effect on ocular and epithelial damage observed through low ocular surface staining score and improved globlet cell density. The PNV treatment was found to more effectively compared to TAC solution and most of the parameters were close to those of healthy animals. In conclusion, tacrolimus PNV formulation (0.01%) could be a potential therapy for treatment of dry eye syndrome.

Topics: Animals; Dry Eye Syndromes; Inflammation; Propylene Glycol; Rabbits; Tacrolimus; Tears

The present study aimed at the development and evaluation of tacrolimus gellan gum nanoparticles (TGNPs) for the effective management of dry eye disease (DED) following topical application. TGNPs were developed by ionotropic gelation between gellan gum and aluminum chloride. Developed TGNPs were nanosized (274.46 ± 8.90 nm) with high % encapsulation efficiency (74.2 ± 2.4%) and loading capacity (36.14 ± 1.7%). The nanosize and spherical morphology of TGNPs was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Fourier transform infrared spectroscopy (FTIR) revealed no interaction between drug and GG. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirms the conversion of crystalline tacrolimus to amorphous post encapsulation in the nanoparticle. TGNPs showed prolonged drug release throughout 12 h and higher pre-corneal retention compared to tacrolimus solution. HET-CAM studies, histopathological evaluation, and Draize test confirmed the safety of the formulation for ocular use. Further, the pharmacodynamic studies using experimental DED in rabbits showed that TGNPs are effective in treating symptoms of DED. In conclusion, topical delivery of TGNPs could hold potential for efficient management of DED.

Topics: Animals; Calorimetry, Differential Scanning; Dry Eye Syndromes; Nanoparticles; Particle Size; Polysaccharides, Bacterial; Rabbits; Spectroscopy, Fourier Transform Infrared; Tacrolimus

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases and has aesthetic, physical, and emotional-social sequelae when left untreated.. To classify the most common adverse reactions associated with dupilumab treatment in patients with AD.. The United States Food and Drug Administration Adverse Event Reporting (FAERS) database was analyzed for common adverse reactions associated with dupilumab, topical pimecrolimus, and topical tacrolimus. Phase III clinical trial data were used to compare the rate of herpes infections between the treatment group and placebo group.. The most common adverse reaction associated with dupilumab was ocular complications. Herpes infections were extremely rare in the patients with AD being treated with dupilumab.. Prescribing information for dupilumab, topical pimecrolimus, and topical tacrolimus is not available. Adverse effects are reported by patients, health care providers, and pharmaceutical companies, they have not been corroborated.. Ocular complications are the most common complication associated with dupilumab. The rate of herpes infection is low in patients being treated with dupilumab, topical pimecrolimus, and topical tacrolimus. There is no significant difference for the rate of herpes infection between, placebo, dupilumab, topical pimecrolimus, and the topical tacrolimus treatment group, suggesting that dupilumab does not affect herpes infection rates.

Topics: Antibodies, Monoclonal, Humanized; Blepharitis; Clinical Trials as Topic; Conjunctivitis; Dermatitis, Atopic; Dry Eye Syndromes; Eye Diseases; Herpesviridae Infections; Humans; Hyperemia; Interleukin-13; Interleukin-4; Retrospective Studies; Tacrolimus; United States; United States Food and Drug Administration; Virus Activation

The sealed anatomical features of the eye and its physiological activity that rapidly removes drugs are called anatomical and physiological barriers, which are the cause of more than 90% of drug loss. This aspect remains a critical issue in eye surface medication. Thus, promoting tissue permeability of drugs as well as prolonging their retention on the eye surface can improve their bioavailability and enhance their therapeutic effects. Thanks to the existence of a negatively charged mucin layer on the eye surface, several peptide-decorated polymeric micelles were prepared to enhance the interaction between the micelle and eye surface, thus prolonging the drug retention on the eye surface and promoting its tissue permeability. Tacrolimus (also known as FK506) is a hydrophobic macrolide immunosuppressant used to treat dry eye syndrome and other eye diseases. However, its hydrophobic nature makes its delivery as a topical eye surface medication difficult, with the risk of side effects due to overdoses. Therefore, the aim of this work is to evaluate the ability of FK506 micelles in promoting their permeability on the eye surface. Our results showed that the positively charged nanomicelles could significantly prolong FK506 retention on the eye surface and enhance its corneal permeability in ex vivo and in vivo conditions. FK506 nanomicelles exhibited superior curing effects against dry eye diseases than the FK506 suspension and a commercial FK506 formula. It exerted better inhibitory effects on eye surface inflammation and corneal epithelium apoptosis when examined by a slip lamp and a transferase-mediated dUTP nick end labeling assay, respectively. Further assays revealed the higher suppressive effects on the expression of several inflammation-related factors at an mRNA and protein level. Hence, our results suggested that these positively charged nanomicelles might be a good drug delivery system for ocular surface medication.

Topics: Administration, Topical; Animals; Cornea; Dry Eye Syndromes; Micelles; Ophthalmic Solutions; Peptides; Permeability; Rabbits; Tacrolimus

To investigate the effect of FK-506 eye drops on Botulinum toxin B (BTX-B)-induced mouse dry eye.. Forty-five CBA/J mice were followed up for 4 weeks after treatment with 0.025% FK-506, vehicle or 0.9% saline eye drops 3 days after intralacrimal glands injection with 20 milliunits BTX-B. Tear production, corneal fluorescein staining, the mRNA, and protein expression of cytokines were measured. The activation of nuclear factor-κB (NF-κB) was detected by Western blotting. The infiltration of inflammatory cells was examined by immunohistochemistry.. After treated with FK-506 eye drops, aqueous tear production in the mice began to recover at week 1, and then increased to the levels of pre-BTX-B injection at week 4 (2.21 ± 0.43 vs. 2.52 ± 0.71 mm, t = 0.84, P > 0.05). The severity of corneal epithelial defects was alleviated at week 2 and further improved at week 4 when compared with those in the vehicle- and saline-treated groups. The gene expression of IL-1β and TNF-α in the FK-506 and vehicle-treated groups were 47.01% and 45.56%, 85.91% and 115.83% of that in the saline-treated group in the ocular surface, while in the lacrimal glands 49.16% and 67.60%, 94.91% and 95.77% of that in the saline-treated group, respectively. The ratio of phosphorylated IκB-α to total IκB-α in the keratoconjunctival tissues was lower in the FK-506-treated group than in the vehicle- and saline-treated groups (both P < 0.05). No inflammatory cells were detected in all groups.. Topical application of FK-506 can inhibit NF-κB activation and related inflammatory response and alleviate the signs of dry eye.

Topics: Animals; Botulinum Toxins, Type A; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Dry Eye Syndromes; Epithelium, Corneal; Female; Follow-Up Studies; Immunosuppressive Agents; Lacrimal Apparatus; Mice; Mice, Inbred CBA; Ophthalmic Solutions; Tacrolimus

We investigate the efficacy of 0.03% topical tacrolimus eyedrops for the treatment of dry eye in graft versus host disease (GVHD) patients resistant/intolerant to 0.05% topical cyclosporine.. Forty-three patients were enrolled in this prospective study. After completing a 1-year run-in period of using artificial tears, 50% autologous serum eyedrops, and punctal plug occlusion, all the symptomatic patients (n=29) were treated with 0.05% topical cyclosporine (Restasis(®); Allergan, Inc.). After 1 month, the patients who presented topical or systemic intolerance to cyclosporine were instructed to instill 0.03% topical tacrolimus once a day for 3 months (n=14). All the patients were allowed to continue with their basal dry eye treatment. Visual acuity, fluorescein staining, Schirmer test, fluorescein tear break-up time, and tear meniscus height measurement were evaluated fortnightly (minimum 3 months). Subjective assessments of symptoms were also reported at the beginning and at the end of the study.. Dry eye symptoms and signs improved statistically (P<0.05) and significantly with tacrolimus and cyclosporine topical treatment. No significant differences were observed between both the groups. The mean follow-up time was 12.14±2.69 months (range 10-18 months).. The findings of this prospective pilot study suggest that cyclosporine-intolerant patients with dry eye associated with GVHD can be effectively treated with topical tacrolimus.

Topics: Administration, Ophthalmic; Adult; Bone Marrow Transplantation; Drug Administration Schedule; Dry Eye Syndromes; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Middle Aged; Ophthalmic Solutions; Pilot Projects; Prospective Studies; Tacrolimus; Treatment Outcome

Topics: Administration, Cutaneous; Adolescent; Chronic Disease; Dry Eye Syndromes; Graft vs Host Disease; Humans; Inflammation; Male; Ointments; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tacrolimus; Treatment Outcome

Tacrolimus is an immunosuppressive medication in the class of calcineurin inhibitors that acts by inhibiting T-cell and interleukin-2 activity, and is commonly used after allogeneic organ transplant. We present a patient who used tacrolimus after cadaveric kidney transplant and experienced blurry vision. Ocular examination and patient's course subsequently revealed aqueous tear deficiency as a dose-dependent adverse effect of oral tacrolimus.

Topics: Dry Eye Syndromes; Glomerulonephritis, IGA; Humans; Hypertension; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lacrimal Apparatus Diseases; Male; Middle Aged; Ophthalmic Solutions; Tacrolimus; Vision Disorders; Visual Acuity

Topics: Adult; Chronic Disease; Dry Eye Syndromes; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Tacrolimus; Tears; Treatment Outcome

We present two cases of severe dry eye in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (SCT) who were successfully treated by the systemic administration of FK506 and corticosteroids.. A 29-year-old man with chronic myelogenous leukemia underwent SCT. Oral and lung CGVHD developed on approximately day 130, and dry eye associated with CGVHD was diagnosed on day 168. The patient began receiving cyclosporin A (150 mg/d) for the treatment of oral and lung CGVHD. Treatment with prednisolone (1 mg/kg/d) began on approximately day 300. Oral and lung GVHD improved slightly, but worsened again although systemic administration of cyclosporin A and prednisolone were continued. Cyclosporin A was discontinued, and systemic administration of FK506 was started on day 376. Forty-four days later, marked improvement in the ocular surface and other organs was observed. However, the dry eye worsened while tapering FK506, with no flare of other affected organs. A 43-year-old woman with myelodysplastic syndrome underwent SCT. She received FK506 for prophylaxis of CGVHD. She had mild dry eye before SCT. Oral and intestinal CGVHD developed, and the dry eye worsened significantly on approximately day 150 while tapering FK506. Treatment with prednisolone (1 mg/kg/d) began, and the dose of FK506 was increased. By day 240, the symptoms of dry eye and the findings of the ocular surface markedly improved, and CGVHD in other organs was completely resolved. However, the improvement in the dry eye was lost when FK506 was tapered for the second time.. Systemic administration of FK506 with corticosteroids is an effective treatment of severe dry eye in patients with CGVHD, but long-term administration may be required to achieve a lasting response. These cases also suggest that further investigation into the use of topical FK506 and prednisolone as a maintenance therapy should be pursued.

Topics: Adult; Chronic Disease; Drug Therapy, Combination; Dry Eye Syndromes; Female; Glucocorticoids; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Myelodysplastic Syndromes; Prednisolone; Tacrolimus