Tacrolimus Eye Drops Research Articles

Clinical Effectiveness, Safety, and Compliance of Two Compounded Formulations of Tacrolimus Eye Drops: An Open-Label, Sequential Prospective Study.

Ophthalmic tacrolimus compounded formulations are usually made from the commercial intravenous presentation, which contains ethanol as a solubilizer due to the low solubility of tacrolimus. The use of cyclodextrins is presented as an alternative to ethanol, an ocular irritant excipient, to avoid its long-term irritant effects. Open-label, sequential, prospective study to compare effectiveness, safety, and adherence of a new formulation of 0.015% tacrolimus with cyclodextrins (TCD) versus 0.03% tacrolimus with ethanol (TE). The ocular evaluation was assessed by ocular signs, corneal staining, subjective questionnaires as Visual Function Questionnaire (VFQ-25) and Visual Analogue Scale (VAS) of symptoms, lacrimal stability, ocular redness, and intraocular pressure. Compliance was assessed by VAS of adherence and empirically (difference between theoretical and actual consumption). Clinical ocular signs and corneal staining score remained stable for most patients 3 months after switching formulations. The TCD formulation did not modify the tear stability and intraocular pressure of the treated patients compared to the TE formulation. TCD eye drops significantly decreased the subjective pain values on VFQ-25 scale and burning sensation on the VAS symptom scale in comparison to TE formulation after 3 months after the change to TCD formulation. The novel tacrolimus in cyclodextrins formulation is a promising alternative for treating inflammatory ocular pathologies refractory to first-line treatments.

The outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome: case series

PurposeTo summarize the outcomes of corneal sight rehabilitating surgery in Stevens-Johnson syndrome (SJS).MethodsThis is a retrospective analysis of a consecutive case series. Twenty-four eyes of 18 SJS patients were included in this study. The ocular parameters, surgical procedures, postoperative complications, and additional treatments of the cases were reviewed.ResultsA total of 29 corneal sight rehabilitating surgeries, which consists of 9 keratoplasties, 8 Keratolimbal allograft (KLAL) and 12 combined surgeries (keratoplasty and KLAL simultaneously) were performed on the 24 eyes. All patients were treated with glucocorticoid eyedrops and tacrolimus eyedrops for anti-rejection treatment without combining systemic immunosuppression, except two patients who were prescribed prednisone tablets for the management of systemic conditions. The mean follow-up period was 50.6 ± 28.1 months. The optimal visual acuity (VA) (0.74 ± 0.60 logarithm of the minimum angle of resolution [logMAR]) and endpoint VA (1.06 ± 0.82 logMAR) were both significantly better than the preoperative VA (1.96 ± 0.43 logMAR) (95% CI, p = 0.000). 57.1% patients (8/14) were no longer in the low vision spectrum, and 88.9% patients (8/9) were no longer blind. The mean epithelialization time was 7.1 ± 7.6 weeks. The success rate was 86.7%. Additional treatments for improving epithelialization included administration of serum eyedrops (n = 10), contact lens (n = 15), amniotic membrane transplantation (n = 6), and tarsorrhaphy (n = 8). Complications included delayed epithelialization (n = 4, over 12 weeks), glaucoma (n = 11), and severe allograft opacity (n = 4). Only one graft rejection was observed.ConclusionsKeratoplasty and KLAL can remarkably enhance VA and improve low vision or even eliminate blindness for ocular complications of SJS. The outcome of the surgeries was correlated with the preoperative ocular situation and choice of operative methods.

Efficacy of tacrolimus capsules in patients undergoing high-risk keratoplasty

Purpose: To evaluate the efficacy of tacrolimus capsules in patients undergoing high-risk keratoplasty.
 Methods: 40 high-risk patients who underwent penetrating keratoplasty at The Third Hospital of Hebei Medical University, China between January 2016 and December 2021 were included in this study. These patients were divided into two groups based on the specific immunosuppressant administered post-surgery. Twenty patients were administered oral tacrolimus capsules in conjunction with 0.1 % tacrolimus eye drops, constituting the combination with systemic treatment group (group 1), while another twenty patients were solely administered 0.1 % tacrolimus eye drops, forming the topical treatment group (group 2). The occurrence of rejection, corneal neovascularization, corneal graft edema and visual acuity were documented in both groups.
 Results: In comparison to patients in group 2, patients in group 1 exhibited a significant reduction in rejection rate (p < 0.05). Additionally, the average time of neovascularization in group 1 was delayed and the number of cases was lower (p < 0.05). Furthermore, a smaller proportion of patients in group 1 experienced corneal graft edema (25 vs 60 %, p < 0.05), while a higher percentage of patients in group 1 demonstrated improved visual acuity (90 vs 60 %, p < 0.05).
 Conclusion: Concurrent administration of tacrolimus eye drops and capsules orally effectively mitigates anti-rejection reactions, regulation of neovascularization, management of graft edema and enhancement of visual acuity in high-risk keratoplasty patients when compared to the use of tacrolimus eye drops as a standalone treatment. These results have the potential to stimulate novel avenues of investigation in future clinical research.

Efficacy evaluation of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in the treatment of severe dry eye associated with chronic graft-versus-host disease

Objective: To evaluate the effectiveness and safety of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in treating severe dry eye associated with chronic graft-versus-host disease (cGVHD). Methods: This non-randomized concurrent control trial enrolled 83 eyes from 83 patients with cGVHD-associated severe dry eye. The treatment had two phases. During the initial shock treatment period (0-3 months), 44 patients received 0.05% cyclosporine A eye drops (4 times/day; group A) and 39 patients received 0.1% tacrolimus eye drops (twice/day; group B) alongside basic treatment. In the maintenance treatment period (3-6 months), both groups used 0.05% cyclosporine A eye drops (twice/day) and sodium hyaluronate. Examinations were conducted at 1, 3, and 6 months after treatment initiation, assessing the Ocular Surface Disease Index (OSDI), corneal fluorescein staining (CFS) score, and fluorescein tear break-up time (BUT) for efficacy. visual acuity and intraocular pressure (IOP) were evaluated for safety, and patients' post-medication irritation symptoms were recorded. Results: The study included 52 males and 31 females, aged (28.57±15.67) years. After 1 month of treatment, the CFS score in group A significantly decreased from 10.0 (6.0, 14.0) to 5.0 (3.0, 8.5) (P<0.001). in group B, the CFS score also significantly decreased from 10.0 (6.0, 15.0) to 6.0 (2.0, 10.0), and the BUT increased from 2.0 (1.0, 2.0) s to 2.0 (1.8, 3.3) s (P<0.001). No significant OSDI decrease was observed in either group. No significant differences were found in OSDI, CFS score, and BUT between the two groups. After 3 months, group A showed significant improvement in OSDI, CFS score, and BUT (P<0.05), while group B only demonstrated significant CFS score decrease (P<0.05). OSDI was significantly lower in group A than group B (P<0.05). No significant differences were noted in CFS score and BUT between groups. After 6 months, OSDI, CFS score, and BUT were 18.9 (9.3, 34.2), 7.0 (3.0, 8.5), and 2.0 (1.0, 3.0) s in group A, and 10.9 (3.6, 35.4), 5.5 (2.8, 10.0), and 2.0 (1.0, 10.0) s in group B. In both groups, CFS scores significantly decreased and BUT increased (P<0.05). Visual acuity improved significantly in group A at 1, 3, and 6 months (P<0.05), while no significant changes were seen in group B. Irritation symptoms were transient and self-resolving in both groups. Conclusions: Both 0.05% cyclosporine A and 0.1% tacrolimus eye drops, when combined with local glucocorticoids, exhibited significant anti-inflammatory effects, effectively and safely treating severe dry eye in cGVHD patients. Although the onset of 0.05% cyclosporine A was slower than 0.1% tacrolimus, it offered more stable long-term effects and better symptom improvement.

Treatment of corneal dermoid with lenticules from small incision lenticule extraction surgery: a surgery assisted by fibrin glue.

To observe the clinical efficacy of the combined use of small incision lenticule extraction (SMILE)-derived lenticule patches in corneal dermoid excision, with fixation of the lenticule patches assisted by fibrin glue. Seventeen eyes of 17 patients with corneal dermoid were treated with dermoid removal combined with SMILE-derived lenticule transplantation. All lenticule patches were fixed by fibrin glue. Ocular changes were assessed using slit lamp microscopy and anterior-segmental optical coherence tomography. The best-corrected visual acuity (BCVA) and ocular dioptric variations were examined preoperatively and postoperatively. Intraocular pressure (IOP) was also monitored in all visited time. Totally, 18 lenticule patches were used on 17 eyes of 17 cornea dermoid patients. The mean follow-up time was 11.47±5.28mo. All lenticule patches were successfully glued, kept on its location and maintained transparent during the follow-up time, with a consecutive epithelial cover for 1wk. Nine of the patients could coordinate visual and optometry exam well. Their preoperative BCVA is 0.60±0.35 in decimal, significantly improved to 0.80±0.26 in decimal at 6mo postoperatively (Z=-2.392, P=0.017), but the changes of their corneal astigmatism diopters showed no significance, with 2.22±1.91 D preoperatively, and 2.28±1.31 D at 6mo postoperatively (Z=-0.135, P=0.893). Limbal pannus formation occurred in 4 (23.52%) cases and decreased with the application of tacrolimus eyedrops. IOP increased in 2 (11.76%) cases, but well decreased by timolol maleate eyedrops. All the adult patients or guardians of minor patients were satisfied with the cosmetic improvement. Dermoid excision combined with transplantation of SMILE-derived lenticule patches using fibrin glue is a safe and effective novel tectonic keratoplasty procedure for corneal dermoid.

Vernal keratoconjunctivitis: Breaking the shield

Abstract A 17-year-old male patient presented with complaints of redness, pain and photophobia in the right eye for a week and itching in both eyes for a year. He was previously diagnosed as vernal keratoconjunctivitis (VKC) a year ago and had discontinued treatment. He was diagnosed as Both eyes VKC, with right eye shield ulcer. He was started on a combination of topical steroids, Tacrolimus and olopatadine eye drops. He started responding to treatment in a weeks’ time and in a month the ulcer healed completely with a vision of 6/6.

IL-33-induced keratoconjunctivitis is mediated by group 2 innate lymphoid cells in mice

BackgroundInterleukin-33 (IL-33) is involved in type 2 innate immunity by inducing type 2 cytokines, such as IL-5 and IL-13, through the activation of group 2 innate lymphoid cells (ILC2s) or T helper 2 (Th2) cells. We previously reported that mice overexpressing IL-33 (IL-33Tg) in the cornea and conjunctiva spontaneously develop atopic keratoconjunctivitis-like inflammation. Despite previous studies, it is not fully understood what types of immune cells contribute to the disease process of IL-33-induced keratoconjunctivitis. MethodsTo defect Th2 cells, IL-33Tg mice were crossed with Rag2KO mice. To defect ILC2s, IL-33Tg mice received bone marrow transplantations from B6.C3(Cg)-Rorasg/J mice that lacked ILC2. Immunostaining techniques were used to determine where ILC2 is distributed in the cornea and conjunctiva. We analyzed the transcriptomes of ILC2 from the conjunctiva by using single-cell RNA-seq analysis. To investigate whether tacrolimus reduces type 2 cytokine production by ILC2, ILC2 was cultured with tacrolimus, and the percentage of cytokine-producing ILC2 was examined. To investigate whether tacrolimus can inhibit IL-33-induced keratoconjunctivitis in vivo, IL-33Tg mice were treated with tacrolimus eye drops. ResultsILC2 infiltrated the conjunctival epithelium and subepithelial tissue. Keratoconjunctivitis developed spontaneously in Rag2KO/IL-33Tg mice, but keratoconjunctivitis was abolished in IL-33Tg mice lacking ILC2. ILC2 was not a uniform cluster but a heterogeneous cluster. Tacrolimus inhibited cytokine production from ILC2s in vitro, and tacrolimus eye drops inhibited keratoconjunctivitis in IL-33Tg mice in vivo. ConclusionsILC2 plays a pivotal role in IL-33-induced keratoconjunctivitis in mice.

Incremental Concentrations of Tacrolimus Eye Drops as a Strategy for the Management of Severe Vernal Keratoconjunctivitis.

Purpose: To assess the effect of different concentrations of tacrolimus eye suspension on the epithelium and stromal keratocytes of human corneas and investigate whether it can be safely used for severe cases of vernal keratoconjunctivitis (VKC). Methods: Tacrolimus eye suspension was prepared in a range of concentrations of 0.005%, 0.01%, 0.05%, 0.1%, and 0.2%. Molecular analysis was performed ex vivo on human corneas (n = 18), obtained from the eye bank. Transparency and thickness of each cornea were measured while live/dead staining was performed using a triple labeling assay. An incremental concentration approach was then tested on three severe cases of VKC. Results: All tested tacrolimus concentrations showed no significant changes in corneal thickness or transparency. In corneas treated with 0.1%, rare scattered dead cells were observed, while the folds of corneal surfaces were mostly viable, unlike concentrations higher than 0.1% and lower than 0.05%. Stromal cell densities were highest in the 0.1% tacrolimus treatment condition. Incremental concentrations of tacrolimus suspension were shown to significantly improve VKC cases, where the concentration used for each case depended on the severity of the case. Conclusions: Topical administration of tacrolimus was not toxic to human corneal cells at all tested concentrations, and the 0.1% concentration has shown the best viability of the corneal tissue. Tacrolimus eye suspension was shown to be safe and effective for use in severe VKC and is proposed as a topical ocular immunosuppressant drug enabling clinicians to incrementally increase the drug concentration according to the clinical severity of the disease to achieve the optimal therapeutic response.

Topical pharmacologic interventions versus placebo for epidemic keratoconjunctivitis.

Topical pharmacologic interventions versus placebo for epidemic keratoconjunctivitis.

Pseudopterygium in a Rabbit - Treatment with Tracolinus

Background: Pseudopterygium, also known as aberrant conjunctival growth, is poorly described in the literature, although it is known that this abnormality is uncommon and affects dwarf rabbits and their crossbreeds. The etiology of this disease is unknown, but there are hypotheses that the conjunctival growth cause may have its origins in immunological factors, inflammation, traumatic conditions, or cartilage dysplasias. Thus, this study reports the treatment efficacy applied in a rabbit, through the continuous use of tracolimus eye drops, after surgical procedure of conjunctival fold resection, as a way of controlling the pseudopterygium in rabbits.Case: This case report discusses the positive results from the surgical and therapeutic conduct of a clinical case attended by the Ophthalmology and Microsurgical Veterinary Service at the Hospital Veterinário Universitário (HVU) of the UFSM. The patient was a male rabbit, sterilized cunicle, approximately 2-year-old, crossed with a dwarf rabbit. The owner's main complaint was the change in the aspect of the left eye, with progressive worsening in the previous four weeks. In the ophthalmological examination, the animal did not present impaired vision or discomfort, however, a vascularized pink membrane was noted, which consisted of a fold of the bulbar conjunctiva, that grew centripetally and covered 90% of the cornea in 360 degrees. The diagnosis was confirmed through visual inspection and the patient's history. The eye alteration had a characteristic aspect, described as proliferation of the bulbar conjunctiva over the cornea, in a centripetal manner and without signs of inflammation. In addition, other ophthalmological alterations were ruled out during the patient's physical and specific examination. The patient was referred for anesthetic evaluation and, in addition, pre-surgical blood tests were performed, which were normal, according to the expected ranges for the species. Subsequently, the animal was submitted to surgical treatment, which consisted of dividing the exuberant conjunctiva, followed by three radial incisions in equal portions. Next, the conjunctival fold was completely incised to the edge of the limbus, without the need of sutures. Anterior lamellar keratectomy was performed on the portion where the membrane was attached to the cornea. For home care, tobramycin-based eye drops (QID, for 7 days) and 0.02% aqueous tacrolimus eye drops (BID - continuous use) were prescribed. The animal was reevaluated 7, 14, 30, 60, 120 and 180 days after surgical correction, and no recurrence of pseudopterygium was observed during the follow-up period. The prognosis of patients with pseudopterygium is reserved, as it is known that the disease may recur after surgical treatment. Therefore, the continuous use of the chosen immunomodulating eye drops was recommended as well as periodic follow-up of the patient.Discussion: In the current study, it was not possible to increase knowledge regarding about the pseudopterygium etiology. Although the condition is not serious, it can cause partial impairment of vision and chronic discomfort. However, the vision field described in the rabbit in this current case remained unchanged, in accordance with other cases described in the literature. Furthermore, no signs of patient discomfort were detected. Some surgical techniques described in the literature for correction of pseudopterygium, shows membrane’s growth recurrence. The use of immunomodulatory drugs is suggested for relapses controlling. In this study, the tracolimus eye drops efficacy was tested, and presented good results in the patient's evaluations for a long period after surgery. The use of immunomodulators is an option for adjuvant topical treatment for controlling pseudopterygium growth, which, associated with corrective surgical treatment, has shown positive results.Keywords: conjunctiva, aberrant, immunomodulator, treatment, bunny.Título: Pseudopterígio em coelho - tratamento com tracolimusDescritores: conjuntiva, aberrante, imunomodulador, tratamento, coelho.

Combination of 0.05% Azelastine and 0.1% Tacrolimus Eye Drops in Children With Vernal Keratoconjunctivitis: A Prospective Study.

Aims: To compare the efficacy of the combination of 0. 05% azelastine and 0.1% tacrolimus eye drops with 0.1% tacrolimus monotherapy in pediatric patients with vernal keratoconjunctivitis (VKC).Methods: Prospective study. Seventy-six patients with VKC were randomized 1:1 into monotherapy group with 0.1% tacrolimus or combination therapy group with 0.1% tacrolimus and 0.05% azelastine. The Ocular Surface Disease Index (OSDI) scores and the signs of conjunctival hyperemia, corneal involvement, and palpebral conjunctiva papillae were assessed at baseline and at 1, 2, and 6 weeks after treatment.Results: Two groups were comparable in age, sex, duration of VKC, OSDI, and clinical signs of VKC at baseline. Significant improvements in OSDI score and clinical signs were observed in both groups at all follow-up visits (all p < 0.001), compared with baseline. The combination therapy group showed a larger decrease in OSDI score from baseline (10.30 ± 0.9) compared with monotherapy group (7.30 ± 0.7, p =0.0085) at 1 week. Greater improvements in conjunctival hyperemia and conjunctival papillae were identified in the combination therapy group, compared with in the monotherapy group, at all follow-up visits (all p < 0.05). The corneal involvement scores in the combination group is significantly lower than the monotherapy group at 2 weeks after the treatment (p = 0.0488). No severe adverse effect was found in either group during the study.Conclusions: Compared with a monotherapy of 0.1% tacrolimus, the combination of 0.05% azelastine and 0.1% tacrolimus eye drops lead to faster and greater improvements in clinical signs and symptoms of vernal keratoconjunctivitis in pediatric patients.

Efficacy of Topical Tacrolimus 0.05% Suspension in Steroid-Resistant and Steroid-Dependent Vernal Keratoconjunctivitis

Objective: The purpose of this study was to investigate the safety and effectiveness of topical tacrolimus 0.05% suspension in the management of prolonged steroid-dependent and -resistant vernal keratoconjunctivitis (VKC). Materials and methods: The present interventional prospective case series were conducted on the research units suffering from refractory VKC between 2017, April and 2020, December. Despite routine drug treatment, consisting of topical steroids (steroid-resistant group), all subjects exhibited active symptomatic illness or were dependent on topical steroids (steroid-dependent group). After discontinuation of all medications for at least 1 week, the patients received eye drop (topical tacrolimus 0.05%) minimally for six months. Objective and subjective signs and symptoms were examined for alterations after one week, and one and six months of treatment. Analyses were continued for probable systemic and ocular adverse effects. Results: The study included 28 eyes of 14 participants (including 4 females and 10 males), with the mean age of 22 ± 8 years (between 11 and 38 years), and the mean VKC duration of 12 ± 6 years (between 5 and 23 years), as well as follow up period of 10±2 months (between 6 and 12 months). The results showed an improvement (P&lt;0.001) in the symptoms such as mucus discharge, foreign body sensation, photosensitivity, redness, burning and itching. The initial sign was conjunctival hyperemia, which improved one week after treatment. Other objective signs including, conjunctival and limbal papillary hypertrophy, corneal pannus and corneal punctate epithelial erosions improved at least one month after treatment. No changes were observed in corneal opacity during follow-up (p&gt; 0.05). There were no systemic or ocular adverse effects. Conclusion: This is the first time that tacrolimus suspension drops 0.05%, are used in these cases. Topical tacrolimus 0.05% was shown to be an effectiveness and safe agent to treat the refractory VKC. This drug is recommended to be prescribed prior to the appearance of side effects such as corneal opacity, irreversible deficiency in limbal stem cell, and steroid side effects. Keywords: Vernal keratoconjunctivitis, Tacrolimus eye drop, Refractory

Long-term outcomes of 0.1% tacrolimus eye drops in eyes with severe allergic conjunctival diseases

BackgroundBecause atopic dermatitis does not heal completely, associated severe atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) often require long-term treatment. This study aims to evaluate the long-term outcomes of using 0.1% tacrolimus eye drops to treat these severe allergic conjunctival diseases.MethodsTwo-hundred-and-seventy eyes of 135 patients diagnosed with AKC or VKC from April 2004 to April 2014 were screened retrospectively. Patient demographics and objective signs were extracted from the electronic medical records. The severity of 10 objective signs, related to the palpebral and bulbar conjunctiva, limbus, and cornea, and intraocular pressure (IOP) were observed at baseline, at 2 weeks, 1, 2, 3, 6, and 12 months after starting treatment, and every 1 year thereafter (average use period: 8.4 ± 2.9 years). Safety was evaluated based on the incidence and severity of adverse events.Results12 patients (AKC; 7 cases, VKC; 5 cases) who were treated with 0.1% tacrolimus eye drops were enrolled in this study. The total score of clinical signs significantly decreased after 2 weeks and remained effective thereafter. Tacrolimus eye drops elicited a statistically significant difference in the mean total clinical scores and IOP over the course of treatment (P < 0.001). Elevated IOP was observed in 2 cases and corneal infection in 1 case; these effects were completely controlled with medication.ConclusionsTopical tacrolimus may provide effective and long-term improvement in clinical signs of severe AKC and VKC cases that refractory to standard conventional treatment.Trial registration: University Hospital Medical Information Network (UMIN) 000034460.

Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop.

Uveitis is a vision inflammatory disorder with a high prevalence in developing countries. Currently, marketed treatments remain limited and reformulation is usually performed to obtain a tacrolimus eye drop as a therapeutic alternative in corticosteroid-refractory eye disease. The aim of this work was to develop a mucoadhesive, non-toxic and stable topical ophthalmic formulation that can be safely prepared in hospital pharmacy departments. Four different ophthalmic formulations were prepared based on the tacrolimus/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes’ formation. Phase solubility diagrams, Nuclear Magnetic Resonance (NMR) and molecular modeling studies showed the formation of 1:1 and 1:2 tacrolimus/HPβCD inclusion complexes, being possible to obtain a 0.02% (w/v) tacrolimus concentration by using 40% (w/v) HPβCD aqueous solutions. Formulations also showed good ophthalmic properties in terms of pH, osmolality and safety. Stability studies proved these formulations to be stable for at least 3 months in refrigeration. Ex vivo bioadhesion and in vivo ocular permanence showed good mucoadhesive properties with higher ocular permanence compared to the reference pharmacy compounding used in clinical settings (t1/2 of 86.2 min for the eyedrop elaborated with 40% (w/v) HPβCD and Liquifilm® versus 46.3 min for the reference formulation). Thus, these novel eye drops present high potential as a safe alternative for uveitis treatment, as well as a versatile composition to include new drugs intended for topical ophthalmic administration.

Tacrolimus dye drop treatment for the management of early post-operative intraocular inflammation after therapeutic keratoplasty for severe infectious keratitis.

The current study investigated the anti-inflammatory effect of 0.1% tacrolimus eye drops for the treatment of therapeutic penetrating keratoplasty (TPK) for severe infectious keratitis during early disease stages and reported the long-term clinical outcomes. The present retrospective study included 20 eyes from patients diagnosed with severe keratitis who underwent TPK surgery. Patients were followed-up for up to 12-18 months. Tacrolimus eye drops were administered 4 times/day starting on the first day post-surgery. Glucocorticoid eye drops were subsequently added to treatment plans one-month post-surgery. All patients were followed-up for the first 3 post-operative days, then examined once a week thereafter for the first month. In early post-operative stages, the states of the grafts (ΔS) and the absorption of intraocular inflammation (S) were observed. ΔS was defined as the difference between the states of the grafts on the first post-operative day (SS1d) and those at one month post-surgery (SS1m). S was calculated as the difference between the inflammation score mean one day post-surgery (T1d) and the mean one-month post-surgery (T1m). For long term clinical outcomes, graft failure rates and complications were recorded. Among the 20 eyes analyzed, the mean T1d, T1m and S were 7.4±2.06, 2.0±2.47 and 5.4±2.13 (P<0.01), respectively. The mean SS1d, SS1m and ΔS were 5.3±1.56, 3.8±1.24 and 1.5±1.5 (P<0.01), respectively. During follow-up, there were 6 cases of corneal graft failure, 4 of which were due to immune rejection and 2 of which were due to complications. The current study concluded that tacrolimus eye drops facilitated the absorption of intraocular inflammation in the early post-operative period of TPK and may extend long term survival of grafts in cases of severe infectious keratitis.

Carboxymethyl Cellulose-Coated Tacrolimus Nonspherical Microcrystals for Improved Therapeutic Efficacy of Dry Eye.

Dry eye (DE) is a highly prevalent ocular surface disease which affects the quality of life and results in low working efficiency. Frequent instillation is required due to low bioavailability of conventional eye drops. The aim of this study is to develop a novel formulation of tacrolimus (TAC), routinely prescribed for DE, by combination of the microcrystal technology and layer-by-layer assembly. First, nonspherical tacrolimus microcrystals (TAC MCs) are synthesized by antisolvent-induced precipitation. These TAC MCs are modified by alternate deposition of poly(allylamine hydrochloride) (PAH) and carboxymethyl cellulose (CMC) subsequently to obtain CMC-coated TAC MCs (TAC-(PAH/CMC)3 ). The resultant formulations are evaluated in vivo in a mouse DE model induced by an intelligently controlled environmental system. Compared with commercially available TAC eye drops and the TAC MCs counterpart, TAC-(PAH/CMC)3 exhibits superior therapeutic performance with reduced drug instillation frequency, which is attributed to the nonspherical geometry of MCs, the lubricant, mucoadhesive effect of CMC, and the anti-inflammatory function of TAC. Therefore, TAC-(PAH/CMC)3 represents a better option for the management of DE.

Experience With 0.1% Tacrolimus Eye Drop for Noninfectious, Non-necrotizing Anterior Scleritis.

To report experience with 0.1% tacrolimus eye drops in the treatment of noninfectious, non-necrotizing anterior scleritis. This prospective, single-arm study included nine patients (4 men and 5 women; mean age=59.4 years, SD=10.5) with anterior scleritis. All patients were first treated with steroids for 1 month and then switched to tacrolimus eye drops alone. We defined baseline as the initiation of tacrolimus eye drops. Hyperemia and pain were scored before each treatment, at 1 and 2 weeks, and at 1 month after initiation of each treatment using 5 grades (0=none; 1+=mild; 2+=moderate; 3+=severe; 4+=extremely severe). Intraocular pressure (IOP) was also measured during treatment with each drug. Safety was assessed based on the severity and the incidence of adverse events. The scores of hyperemia and pain had significantly decreased from baseline by 1 week after initiating tacrolimus eye drops (both P<0.05). No significant reduction was observed with steroid treatment throughout the 1-month period in both scores. Tacrolimus eye drops elicited statistically significant differences in mean IOP over the course of treatment (P=0.02). No additional medications were required to provide relief in any of the patients receiving tacrolimus treatment. No patient demonstrated infectious adverse events after initiation of tacrolimus treatment. Topical tacrolimus may effectively and immediately reduce clinical signs and symptoms of noninfectious, non-necrotizing anterior scleritis in cases unresponsive to a course of topical steroid.

Preliminary In Vivo Safety Evaluation of a Tacrolimus Eye Drop Formulation Using Hydroxypropyl Beta Cyclodextrin After Ocular Administration in NZW Rabbits.

AimTacrolimus is an immunosuppressive drug with higher potency compared to cyclosporine A (as a useful immunosuppressant). We prepared an ophthalmic solution formulation of Tacrolimus using hydroxypropyl beta cyclodextrin (HP-ßCD). In the present study, safety of this formulation was investigated in rabbits.Materials and MethodsFormulation containing HP-ßCD, Tacrolimus, Polyvinyl alcohol (PVA) and Benzalkonium Chloride in PBS 7.4 was prepared. Tacrolimus concentration in ophthalmic preparation was 0.05% w/v. Ten male New Zealand white rabbits were housed in clean separated cages. One drop of Tacrolimus prepared formulation and a placebo formulation were applied every 12 hrs in the right and left eyes respectively, for 28 days.ResultsThis new aqueous formulation of Tacrolimus could improve Tacrolimus solubility about 42 times. Clinical examinations on the 1st, 3rd, 7th, 14th and 28th days of study showed transient redness and conjunctivitis in some cases of both control and intervention groups that was not persistent. At the end of the study, there were no statistical differences between the two groups in corneal epithelial defect, redness or pathological evaluations.ConclusionThe results of this study suggest that eye drop formulation of CD-Tacrolimus is safe in preliminary evaluations and can be useful for further studies.

角膜移植术后使用他克莫司滴眼液、环孢素滴眼液对角膜厚度影响的分析

角膜移植术后使用他克莫司滴眼液、环孢素滴眼液对角膜厚度影响的分析

角膜移植术后使用他克莫司眼液与1%环孢素A眼液眼表疾病评分指数的变化

角膜移植术后使用他克莫司眼液与1%环孢素A眼液眼表疾病评分指数的变化