tacrolimus and Keratitis

The objective of this study was to assess the treatment of chronic superficial keratitis (CSK) in dogs with the use of tacrolimus and DMSO. The study was conducted on 16 dogs - 7 males and 9 females, aged 3 to 11 years, diagnosed with CSK. The disease was treated with ophthalmic drops containing 0.02% tacrolimus and 50% DMSO, administered to the ocular surface three times a day. Prior to the treatment and after 5 weeks of therapy, the corneal neovascularisation, pigmentation, and also the redness and depigmentation of the third eyelid margin were assessed. The percentage of the corneal surface afflicted with inflammatory processes was calculated on the basis of photographs taken with the use of IsoCalc.com's Get Area software for Corel DRAW 12. It was found that the application of tacrolimus and DMSO caused a reduction of inflammatory process and neovascularisation in the cornea. The mean corneal surface afflicted with inflammatory processes was statistically significantly reduced from 69.9% to 43.9% (p < or = 0.01)--in case of the right corneas, and from 58.9% to 38.6% in case of the left corneas. Of 32 corneas diagnosed with the pigmentation, the reduction of the pigmentation was observed in 14, while in 16 the pigmentation increased. The treatment of CSK with the use of tacrolimus and DMSO causes the reduction in terms of inflammatory processes and neovascularisation, but in many cases does not inhibit the progress of the pigmentation.

Topics: Animals; Chronic Disease; Dimethyl Sulfoxide; Dog Diseases; Dogs; Female; Free Radical Scavengers; Immunosuppressive Agents; Keratitis; Male; Tacrolimus

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

Corneal nerve fibers provide sensation and maintain the epithelial renewal process. Insufficient corneal innervation can cause neurotrophic keratopathy. Here, topically delivered tacrolimus is evaluated for its therapeutic potential to promote corneal reinnervation in rats.. A compartmentalized neuronal cell culture was used to determine the effect of locally delivered tacrolimus on sensory axon regeneration in vitro. The regenerating axons but not the cell bodies were exposed to tacrolimus (50 ng/mL), nerve growth factor (50 ng/mL), or a vehicle control. Axon area and length were measured after 48 hours. Then, a biodegradable nanofiber drug delivery system was fabricated via electrospinning of a tacrolimus-loaded polycarbonate-urethane polymer. Biocompatibility, degradation, drug biodistribution, and therapeutic effectiveness were tested in a rat model of neurotrophic keratopathy induced by stereotactic trigeminal nerve ablation.. Sensory neurons whose axons were exposed to tacrolimus regenerated significantly more and longer axons compared to vehicle-treated cultures. Trigeminal nerve ablation in rats reliably induced corneal denervation. Four weeks after denervation, rats that had received tacrolimus topically showed similar limbal innervation but a significantly higher nerve fiber density in the center of the cornea compared to the non-treated control. Topically applied tacrolimus was detectable in the ipsilateral vitreal body, the plasma, and the ipsilateral trigeminal ganglion but not in their contralateral counterparts and vital organs after 4 weeks of topical release.. Locally delivered tacrolimus promotes axonal regeneration in vitro and corneal reinnervation in vivo with minimal systemic drug exposure.. Topically applied tacrolimus may provide a readily translatable approach to promote corneal reinnervation.

Topics: Animals; Axons; Cornea; Corneal Dystrophies, Hereditary; Delayed-Action Preparations; Drug Delivery Systems; Keratitis; Nerve Regeneration; Rats; Tacrolimus; Tissue Distribution; Trigeminal Nerve Diseases

We report 3 cases of patients with chronic ocular surface inflammatory disease who developed cytomegalovirus (CMV) corneal endotheliitis during immunosuppressant and steroid treatment.. This is a retrospective observational study analyzing the clinical characteristics and outcomes of 3 patients with ocular surface inflammatory diseases (2 with Mooren ulcer and 1 with idiopathic scleritis) who developed CMV corneal endotheliitis. All patients developed CMV corneal endotheliitis between 8 and 14 months of starting steroid and immunosuppressant treatment, including topical 0.1% tacrolimus. Decimal visual acuity, endothelial counts, and intraocular pressure were analyzed.. All patients received topical 0.5% ganciclovir after the diagnosis of CMV corneal endotheliitis, which improved endothelial inflammation. However, all patients developed irreversible mydriasis and required additional surgeries, including endothelial keratoplasty, cataract surgery, and glaucoma surgery. At the final follow-up (14-46 months post-CMV corneal endotheliitis onset), fair outcomes were achieved, as demonstrated by a mean decimal best-corrected visual acuity of 0.3 and a well-controlled intraocular pressure.. Topical steroids and immunosuppressants can induce fulminant CMV corneal endotheliitis with cataract progression and irreversible mydriasis. In these cases, early diagnosis and treatment, including topical 0.5% ganciclovir, glaucoma surgery, cataract surgery, and endothelial keratoplasty, are necessary for preserving the patient's vision.

Topics: Aged; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Drug Therapy, Combination; Endothelium, Corneal; Eye Infections, Viral; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Keratitis; Male; Retrospective Studies; Tacrolimus

A consecutive case series of patients with dupilumab-associated ocular surface disease (DAOSD) that describes common ocular symptoms and signs, proposes a symptom disease severity grading system, and describes treatment strategies of DAOSD patients was evaluated.. A retrospective chart review of patients with concomitant dupilumab-treated atopic dermatitis and DAOSD with ophthalmic evaluation between January 2014 and May 2019 was conducted.. Twenty-nine patients (mean age 46 years, M/F: 12/17) with 57 ophthalmic exams were identified. The most common ocular symptoms included irritation/pain (n = 28, 97%), redness (n = 24, 83%), pruritus (n = 18, 62%), discharge (n = 18, 62%), and light sensitivity (n = 6, 21%). The most frequent signs included conjunctival injection (n = 18, 62%), superficial punctate keratitis (n = 16, 55%), and papillary reaction (n = 8, 28%). Topical corticosteroids (TCS) (n = 23, 79%), tacrolimus (n = 6, 21%), and artificial tears (n = 7, 24%) were the most commonly used therapies. Of those with follow-up documentation (n = 21), 20 were noted to have partial or complete response with TCS based on symptoms and reduction of signs. Using our proposed symptom-based grading scale, scaled 1 to 5 based on the presence of common symptoms listed above, 66% (n = 19) requiring topical immunomodulating therapy were found in the 'severe' group (≥3 symptoms) and 17% (n = 5) were found in the 'mild' group (≤2 symptoms).. This study provides insight into the commonly presenting ocular signs and symptoms associated with DAOSD and highlights the efficacy of TCS and other immunomodulators in improving symptoms associated with DAOSD. Based on our findings, we propose a symptom-based grading system that can guide nonophthalmic physicians regarding ophthalmology consult.

Topics: Adolescent; Adult; Aged; Anti-Allergic Agents; Antibodies, Monoclonal, Humanized; Child; Conjunctivitis; Dermatitis, Atopic; Eye Pain; Female; Follow-Up Studies; Glucocorticoids; Humans; Keratitis; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Tacrolimus; Treatment Outcome

To evaluate the efficacy of topical tacrolimus 0.02% eye drops in the treatment of patients with Thygeson superficial punctate keratitis.. Ten consecutive patients with Thygeson superficial punctate keratitis were included retrospectively. Seven patients were unresponsive to topical steroids and/or lubricants. Diagnosis was made based on the history and clinical findings. All patients were treated with topical tacrolimus 0.02% solution twice daily. Outcome measures included improvement in symptoms of tearing and photophobia, whereas improvement in signs included decrease in the number of the lesions, resolution of the lesions, flattening of the lesions, and decrease in stain of the lesions.. There were 3 male and 7 female patients with an age range of 3 to 51 years (mean 17 years). All patients had bilateral ocular involvement. Duration of treatment ranged from 1 to 42 weeks (mean 10 weeks). All patients had subjective improvement in symptoms of tearing and photophobia and resolution of the superficial punctate keratitis. The response to treatment was noted 72 hours after initiation of therapy in all patients. Topical tacrolimus was well tolerated in all patients.. Topical tacrolimus 0.02% is safe and effective in reducing ocular surface inflammation in patients with Thygeson superficial punctate keratitis who are not responsive to conventional therapy. Tacrolimus is helpful as a steroid-sparing agent to avoid vision-threatening complications.

Topics: Administration, Topical; Adolescent; Adult; Child; Child, Preschool; Cornea; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Keratitis; Male; Middle Aged; Ophthalmic Solutions; Retrospective Studies; Tacrolimus; Treatment Outcome; Young Adult

A 33-year-old man presented with a four-day history of redness and blurring of vision of the right eye. A clinical diagnosis of adenoviral keratitis was made with a differential of microsporidia epithelial keratitis. The patient subsequently developed nummular keratitis which was resistant to topical steroids. He continued to develop multiple recurrences of the condition. Treatment with tacrolimus ointment was started as the patient had an elevated intraocular pressure due to prolonged steroid use. Tacrolimus ointment showed a favourable outcome in the management of recurrent nummular keratitis.

Topics: Adenoviridae Infections; Adult; Humans; Immunosuppressive Agents; Keratitis; Male; Ointments; Steroids; Tacrolimus; Treatment Outcome

To investigate the expression and roles of type I and II interferons (IFNs) in fungal keratitis, as well as the therapeutic effects of tacrolimus (FK506) and voriconazole on this condition.. After zymosan stimulation of mouse neutrophils, lymphocytes, macrophages, and A6(1) cells, the IFN mRNA and protein expression levels were markedly increased until 24 h, peaking at 8 h (p<0.001). The mRNA and protein expression levels of inflammatory cytokines (IL-1α, IL-6, IL-12, and IL-17) were also upregulated after zymosan stimulation. Moreover, type I (IFN-α/β) and type II (IFN-γ) IFN expression levels were increased and positively correlated with the progression of fungal keratitis in vivo. FK506 administered with voriconazole reduced the pathological infiltration of inflammatory cells into the cornea and downregulated the expression levels of IFNs and related inflammatory cytokines.. In conclusion, this study demonstrated that type I and II IFN levels were markedly increased in fungal keratitis and that FK506 combined with voriconazole decreased the severity of fungal keratitis by suppressing type I and II IFNs and their related inflammatory responses.

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Cornea; Disease Models, Animal; Drug Combinations; Drug Synergism; Epithelial Cells; Eye Infections, Fungal; Female; Gene Expression Regulation; Interferons; Interleukins; Keratitis; Lymphocytes; Macrophages; Mice; Mice, Inbred C57BL; Neutrophils; Severity of Illness Index; Tacrolimus; Voriconazole; Zymosan

Topics: Adult; Cyclosporine; Eye Infections, Fungal; Female; Glucocorticoids; Graft Rejection; Humans; Immunosuppressive Agents; Intraocular Pressure; Keratitis; Keratoplasty, Penetrating; Male; Middle Aged; Ophthalmic Solutions; Postoperative Period; Recurrence; Retrospective Studies; Risk Factors; Tacrolimus; Treatment Outcome

Lipopolysaccharide (LPS)‑induced keratitis is a progressive infectious ocular disease in which innate inflammatory responses often cause clinical tissue damage and vision loss. The present study aimed to investigate the effects of tacrolimus, an effective immunomodulator, on LPS‑induced innate immune responses. The effects of tacrolimus on the apoptotic rate and viability of human corneal epithelial cells (HCECs), polymorphonuclear neutrophils (PMNs) and monocytes (THP‑1 cells) were examined using flow cytome-try and MTT assays. Subsequently, the role of tacrolimus on LPS‑induced inflammation in HCECs, PMNs and THP‑1 cells was evaluated by detecting the expression levels of pro‑inflammatory cytokines, including interleukin (IL)‑1β, IL‑6 and matrix metallopeptidase 9; anti‑inflammatory cytokines, including IL‑10 and transforming growth factor‑β; and proangiogenic factors, including vascular endothelial growth factor and tumor necrosis factor‑α using quantitative polymerase chain reaction. The results demonstrated that tacrolimus had good biocompatibility with HCECs, while promoting apoptosis and decreasing the viability of PMNs and THP‑1 cells. Furthermore, tacrolimus effectively reduced the expression levels of pro‑inflammatory cytokines and increased anti‑inflammatory cytokines in LPS‑induced keratitis in vitro. Notably, tacrolimus decreased the levels of proangiogenic factors, which are highly increased following LPS stimulation. Conclusively, tacrolimus appears to be a safe and effective treatment to suppress neutrophil and monocyte activity, modulate the balance of pro‑/anti‑inflammatory cytokines, and reduce the inflammatory response and angiogenic activity in LPS‑induced bacterial keratitis.

Topics: Adult; Anti-Inflammatory Agents; Cytokines; Female; Gene Expression Regulation; Humans; Immunity, Innate; Inflammation; Keratitis; Lipopolysaccharides; Male; Middle Aged; Monocytes; Neutrophils; Tacrolimus

To evaluate the efficacy of topical tacrloimus eye drops in the treatment of keratitis associated with autoimmune polyglandular syndrome (APS)-1.. This is a retrospective review of 10 patients with APS-1. The patients were treated with topical tacrolimus 0.01% solution at The Eye Center, between 1 March 2012 and 30 April 2016. The outcome measures included improvement in visual acuity, photophobia and keratitis following treatment. Clinical assessment was carried out before, during and on the last visit following initiation of therapy.. A total of 10 patients were included. There were five male and five female patients. The mean age was 11 years with age range of 3-42 years. The mean duration of treatment with topical tacrolimus was 26 months (range 8-46 months). There was improvement of photophobia in 7 out of 10 patients following therapy with topical tacrolimus. In three patients, the photophobia was persistent. There was no clinically detectable improvement in the severity of keratitis in all patients. The mean best corrected visual acuity was 0.1 before and following therapy.. Topical tacrolimus is effective in reducing the photophobia in patients with APS-1-associated keratitis, but showed no effects on the severity of keratitis.

Topics: Administration, Topical; Adolescent; Adult; Child; Child, Preschool; Female; Humans; Immunosuppressive Agents; Keratitis; Male; Ophthalmic Solutions; Photophobia; Polyendocrinopathies, Autoimmune; Retrospective Studies; Tacrolimus; Treatment Outcome; Visual Acuity

To report our findings in a case of childhood refractory interstitial keratitis successfully treated with 0.1% topical tacrolimus.. A 12-year-old boy presented with a 3-year history of interstitial keratitis. For the recurrent interstitial keratitis he had been treated with topical and systemic acyclovir, steroids, and topical cyclosporine for 3 years. Our examinations revealed severe stromal infiltrates and neovascularization. Treatment was changed from topical 0.5% cyclosporine to topical 0.1% tacrolimus combined with topical acyclovir and betamethasone.. After 2 weeks of treatment with topical tacrolimus, the degree of stromal infiltrates decreased. Although the improvements were slow, the stromal infiltrates resolved somewhat, and neovascularization and topical acyclovir and betamethasone were tapered and stopped in 18 months. Since then, the patient has not shown any recurrence for 9 months without medication.. Our findings indicate that topical tacrolimus should be considered for treating refractory interstitial keratitis in children.

Topics: Acyclovir; Administration, Topical; Betamethasone; Child; Cyclosporine; Drug Substitution; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Keratitis; Male; Recurrence; Tacrolimus; Treatment Outcome

To investigate the efficacy and safety of long-term maintenance treatment with tacrolimus ointment in chronic ocular graft-vs-host disease (GVHD) with ocular surface inflammation.. A retrospective interventional consecutive case series.. Long-term maintenance treatment (≥6 months) with topical 0.02% tacrolimus ointment was applied to patients with chronic ocular GVHD with ocular surface inflammation (at least grade 2 inflammatory score). We evaluated the inflammatory score, steroid score and steroid use period of total duration, and numbers of inflammatory aggravations before and after tacrolimus treatment. The clinical outcomes were assessed by symptom score, ocular surface staining, Schirmer I test, tear break-up time (TBUT), and classification of chronic GVHD conjunctivitis at the initial and final examinations.. Thirteen patients (24 eyes) were treated with tacrolimus ointment for up to 20 months (average 12.2 months). The ocular surface inflammatory score decreased from 2.8 to 0.6 (P = .001) within 2-8 weeks after starting tacrolimus ointment treatment. The numbers of inflammatory aggravation and the need for steroid treatment also decreased after initiating tacrolimus treatment. At the final follow-up, all patients reported improvement in clinical outcomes, compared to initial findings. Except for blurred vision or mild burning sensation, there were no reported side effects.. Considering the chronic course of GVHD, long-term maintenance treatment with tacrolimus ointment could be useful and safe to locally treat ocular surface inflammation in chronic ocular GVHD.

Topics: Adolescent; Adult; Child, Preschool; Chronic Disease; Conjunctivitis; Female; Follow-Up Studies; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Keratitis; Leukemia; Male; Middle Aged; Ointments; Retrospective Studies; Tacrolimus; Treatment Outcome; Visual Acuity; Young Adult

To evaluate topical tacrolimus ointment for treating Thygeson's superficial punctate keratitis (Thygeson SPK).. Retrospective interventional case series.. setting: Institutional practice.. The medical records of 14 patients (9 women; age range, 9-65 years) with Thygeson SPK were reviewed retrospectively. Diagnosis was based on the history and clinical examination.. Patients were treated with tacrolimus 0.03% eye ointment instilled into the lower fornix twice daily for the first 2 weeks, followed by nocturnal application. The clinical signs and symptoms were assessed after 1 month of treatment. The drug was tapered with disease improvement.. Treatment efficacy and side effects.. All patients had bilateral disease (average duration, 6 years). All patients, except 2 who used the medication irregularly, had improved visual acuity (VA), symptoms, and signs as long as the medication was applied. Before treatment 28.57% of patients had VA between 20/30 and 20/50, with improvement after treatment to 20/25 or 20/20. Attempts to withdraw the medication resulted in recurrent disease, and, therefore, treatment was not curative during the study period. No significant local medication side effects were reported.. Tacrolimus eye ointment 0.03% was effective for controlling Thygeson SPK for a long period with good patient tolerance and no noticeable local or systemic side effects. During the average 6-year follow-up, treatment was not curative. Randomized studies are difficult to conduct because of the disease rarity.

Topics: Administration, Topical; Adolescent; Adult; Aged; Child; Female; Humans; Immunosuppressive Agents; Keratitis; Male; Middle Aged; Ointments; Ophthalmic Solutions; Retrospective Studies; Tacrolimus; Visual Acuity; Young Adult

The response to treatment with four topical preparations was evaluated in an 11-year-old Morgan horse mare with histologically confirmed quadrilateral cannon hyperkeratosis. Each limb was treated for 30 days with 0.1% tacrolimus ointment, 0.1% adapalene gel, 0.2% phytosphingosine spray or a water-based emollient. Response to treatment was evaluated both histologically and visually. A water-based emollient and 0.1% tacrolimus ointment produced encouraging clinical responses. Pre-treatment histopathology identified marked, mostly compact, hyperkeratosis and follicular hyperkeratosis, most prominent in the infundibular area. Following treatment, histopathology identified a mild reduction in follicular keratin production and stratum corneum thickness.

Topics: Adapalene; Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Horse Diseases; Horses; Immunosuppressive Agents; Keratitis; Naphthalenes; Sphingosine; Tacrolimus

Ocular involvement in cicatricial pemphigoid often occurs from the onset. Certain forms are seen only in this condition.. A 31-year-old woman presented highly inflammatory conjunctivitis for several months associated with bilateral symblepharons and superficial punctuate keratitis around the left eye refractory to treatment. The patient had a history of mouth ulcers and sores on the scalp. Examination showed scalp lesions with crusts. Histological examination of these lesions revealed dermal-epidermal cleavage. Direct immunofluorescence showed sub-membrane deposits. Anti-basal membrane antibodies were positive. Immunotransfer confirmed the presence of circulating antibodies. This condition was controlled following administration of three courses of cyclophosphamide as a bolus. However, the symblepharons persisted in both eyes. Improvement lasted 4 years. The patient again consulted for inflammatory conjunctivitis and superficial punctate keratitis resulting in invalidating loss of visual acuity, associated with hypereosinophilia. Cortisone eye drops alone resulted in no improvement. Treatment was initiated with topical tacrolimus (Protopic) 0.03% comprising once-daily application to the conjunctiva in the evening. This therapy was well tolerated, and 2 daily applications could be given, followed by a dosage of 0.1%. Improvement was rapid and spectacular, with frank amelioration of visual acuity and resolution of the patient's keratitis. Treatment was continued for 4 months and gradually reduced to the 0.03% dosage level, with increasingly wide intervals between applications. There has been no relapse within the 12 months following the end of treatment.. Standard treatment of pharmacological cicatricial pemphigoid involves systemic immunosuppression since topical anti-inflammatories are ineffective. The mortality associated with this disease is due to iatrogenic complications. Tacrolimus exhibits extremely good penetration of the conjunctiva. Following administration at a concentration of 0.06% 3 times daily in 15 patients with inflammatory disease of the conjunctiva or the cornea, improvement was seen in 10 of these patients at 26 weeks. Tacrolimus appears to act through immunomodulatory and anti-inflammatory mechanisms. It induces local inhibition of T lymphocyte activation and reduces production of pro-inflammatory lymphokines. Oral tacrolimus cannot be used to control cicatricial pemphigoid refractory to standard immunomodulators. However, 3 three other cases involving topical treatment of cicatricial pemphigoid showed marked efficacy of treatment given for 2 to 6 months, with complete tolerability. Thus, topical tacrolimus appears to constitute an interesting alternative treatment in cicatricial pemphigoid.

Topics: Administration, Topical; Adult; Conjunctivitis; Cyclophosphamide; Eye Diseases; Female; Humans; Immunosuppressive Agents; Injections, Intravenous; Keratitis; Lymphocyte Activation; Pemphigoid, Bullous; T-Lymphocytes; Tacrolimus; Time Factors; Tissue Adhesions; Treatment Outcome; Visual Acuity

Topical corticosteroids are the only effective measure in serious inflammatory corneal and conjunctival diseases. Although results obtained with topical cyclosporin A are encuraging it is not effective in all patients. The mode of action of Fk506 is similar to that of cyclosporin A, i.e. it exerts an inhibitory effect on transcription of interleukin 2 in T lymphocytes. The immunosuppressive potential of Fk506, however, is much larger. Furthermore, it penetrates more easily into cornea and conjunctiva. To find out whether the theoretical advantages of topical Fk506 can be translated into clinical practice, a selected group of patients refractory to conventional therapy was treated in this pilot study.. Fk506 0.06 % was administered initially three times daily in 15 patients with atopic blepharokeratoconjunctivitis, Mooren's ulcer, ocular pemphigoid, Thygeson's superficial punctate keratitis, nummular adenoviral keratitis, graft-versus-host reaction of the conjunctiva and steroid response glaucoma after penetrating keratoplasty.. Within a follow-up of 26 +/- 15 weeks improvement was recorded in 5/15 patients and stabilization in 5/15 patients. In two patients progression of the disease was noted (one patient with progression of ocular pemphigoid, another patient with suspected automutilation). Premature withdrawal the drug was judged to be necessary in two patients with ocular surface disorders and in one patient with non-compliance.. Topical Fk506 seems to be a promising new immunosuppressive drug for patients with atopic blepharokeratoconjunctivitis, Thygeson's superficial punctate keratitis and nummular adenoviral keratitis. Exact efficacy in these and other corneal and conjunctival inflammatory diseases has to be determined in randomised clinical studies. Before these studies may start the risk of side-effects must be reduced via an improvement of the drops.

Topics: Adult; Aged; Aged, 80 and over; Conjunctivitis; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Interleukin-2; Keratitis; Male; Middle Aged; Ophthalmic Solutions; Pilot Projects; Tacrolimus; Treatment Outcome

We evaluated the efficacy of topical cyclodextrin-encapsulated FK-506 in the prevention of experimental corneal allograft rejection. Two weeks after inducing corneal inflammation and neovascularization with 8-0 silk sutures, 23 albino rabbits received a unilateral 8-mm diameter central penetrating corneal allograft from pigmented donors. Rabbits were randomly assigned to no treatment (eight eyes), topical cyclodextrin four times daily for 28 days (seven eyes), or topical FK-506 0.3 mg/ml in a cyclodextrin suspension (eight eyes) four times daily for 28 days. Grafts were examined daily for degree of inflammation, neovascularization, edema, and signs of rejection for up to 100 days. Seven of eight (88%) untreated grafts and five of seven (71%) cyclodextrin-treated grafts rejected at a median of 3 weeks after transplantation, whereas only two (25%) of eight FK-506-treated grafts rejected and did so at a significantly longer interval (p < 0.005). Topical FK-506 prevents or delays corneal allograft rejection after experimental corneal transplantation.

Topics: Administration, Topical; Animals; Corneal Neovascularization; Cyclodextrins; Disease Models, Animal; Drug Carriers; Graft Rejection; Graft Survival; Keratitis; Keratoplasty, Penetrating; Ophthalmic Solutions; Rabbits; Random Allocation; Tacrolimus; Transplantation, Homologous

Topics: Female; Humans; Inflammation; Keratitis; Middle Aged; Syndrome; Tacrolimus; Vasculitis; Vestibular Diseases