Topical tacrolimus for high-risk corneal transplantation: a randomized, clinical trial.

BACKGROUND: The prevalence of rejection is 10-30% in penetrating keratoplasty (PKP) case, and the rate is higher in cases of high-risk patients. Although using topical corticosteroids is a standard method for management the rejection of post-PKP patients, it may not be sufficiently potent in high-risk patients. Topical administration of tacrolimus (TAC) may be effective in suppression rejection after corneal transplantation. This study aimed to investigate the efficacy and safety of topical TAC in high-risk PKP patients in Japan. METHODS: This study was a single centre, single-blinded, randomized controlled trial. Patients with a history of PKP, graft rejection, atopic dermatitis, or deep corneal neovascularisation who underwent PKP were enrolled. They were randomly assigned to receive 0.1% TAC ophthalmic suspension or artificial tear (AT) up to week 52 after surgery. All participants received 0.1% betamethasone up to week 13 after surgery then they received 0.1% fluorometholone up to week 52. The incidence of immunological rejection during the observation period was the main outcome measure in this study. RESULTS: Thirty patients were enrolled in this study, and 12 eyes in the TAC group and 13 eyes in the AT group completed the study, respectively. Five out of 30 patients discontinued participation after providing informed consent. No serious adverse effects were developed in patients who received 0.1% TAC ophthalmic suspension. No rejection episodes occurred in the TAC group, while one eye in the AT group had rejection. Graft clarity, best spectacle-corrected visual acuity, intraocular pressure, and corneal endothelial cell density were not significantly different between the TAC and AT groups. CONCLUSION: Our results demonstrated that good tolerability of 0.1% TAC ophthalmic suspension. However, we failed to demonstrate its efficacy in preventing immunological rejection in high-risk patients undergoing PKP. TRIAL REGISTRATION: This study was first registered in the University Hospital Medical Information Network (UMIN000029669, Date of registration: November 1, 2017). With the enforcement of the Clinical Trial Act in Japan, the study re-registered in the Japan Registry of Clinical Trials (jRCTs031180342, Date of registration: March 18, 2019).

Efficacy and safety of topical azithromycin therapy in patients with blepharitis and meibomian gland dysfunction.

PURPOSE: To assess the effects of 1% azithromycin ophthalmic solution (AZM) in patients with bacterial blepharitis accompanied by meibomian gland dysfunction (MGD). STUDY DESIGN: A multicenter, single arm, prospective interventional study. METHODS: AZM was administered to the affected eyes twice daily for the first 2 days and once daily for the subsequent 12 days. Lid margin hyperaemia/redness, collarette at the root of the eyelashes, conjunctival hyperaemia, foreign body sensation, and epiphora were assessed on Days 1, 14, and 28. The Dry Eye-related Quality of Life Score (DEQS) and objectives related to MGD, including lid vascularity, lid margin irregularity, foaming, lid plugging, keratoconjunctival disorders, Marx line, meibum grade, and tear breakup time, were also assessed. Bacterial culture of the conjunctival sac and meibum was performed on Days 1 and 14. RESULTS: Twenty-four eyes of 24 patients (10 men/14 women, mean age 72.3 ± 13.2) were included. On Days 14 and 28, the total score, lid vascularity, lid plugging, and meibum grade showed significant improvement (p < 0.05). On Day 1, 71 strains were isolated from 22 of the 24 eyes (91.7%). Cutibacterium acnes, Corynebacterium spp., and Staphylococci were detected at high frequencies. The overall disappearance rates of the bacteria in the conjunctival sac and meibum at the end of treatment were 65.7% and 58.3%, respectively. No serious ocular or systemic adverse events were observed. CONCLUSION: Fourteen-day treatment with AZM was effective in patients with blepharitis accompanied by MGD, and the efficacy of AZM persisted for a period after the treatment.

Therapeutic Aqueous Humor Concentrations of Latanoprost Attained in Rats by Administration in a Very-High-Molecular-Weight Hyaluronic Acid Eye Drop.

The temporal change in concentration of a novel medicine, Latanoprost (LP), was evaluated in the aqueous humor of rats (6-8-week-old Jcl:Wister rats) when delivered in a very-high-molecular-weight hyaluronic acid (vHiHA) eye drop. Animals were randomly assigned to three treatment groups (LP + vHiHA (LPvHiHA), commercial LP (cLP), and diluted LP (dLP)) and after instilling the eye drops, the aqueous humor (AH) was collected at 0.5, 1, 2, 4, and 6 h to measure the LP concentration using an enzyme-linked immunosorbent assay (ELISA). Although the LP concentration in the LPvHiHA eye drop formulation was 3.57 times lower than in the commercial eye drops used (cLP), the LP concentration in the AH following LPvHiHA administration reached a value close to that of cLP. The cLP was diluted to the same concentration of LP as in the LPvHiHA eye drops for the dLP group, but the LP concentration in the AH of these animals was lower than that of the LPvHiHA rats at all time points. The higher LP concentration in the AH of the LPvHiHA rats suggests that vHiHA may aid the transport of LP across the ocular surface epithelium.

Deep learning model for extensive smartphone-based diagnosis and triage of cataracts and multiple corneal diseases.

AIM: To develop an artificial intelligence (AI) algorithm that diagnoses cataracts/corneal diseases from multiple conditions using smartphone images. METHODS: This study included 6442 images that were captured using a slit-lamp microscope (6106 images) and smartphone (336 images). An AI algorithm was developed based on slit-lamp images to differentiate 36 major diseases (cataracts and corneal diseases) into 9 categories. To validate the AI model, smartphone images were used for the testing dataset. We evaluated AI performance that included sensitivity, specificity and receiver operating characteristic (ROC) curve for the diagnosis and triage of the diseases. RESULTS: The AI algorithm achieved an area under the ROC curve of 0.998 (95% CI, 0.992 to 0.999) for normal eyes, 0.986 (95% CI, 0.978 to 0.997) for infectious keratitis, 0.960 (95% CI, 0.925 to 0.994) for immunological keratitis, 0.987 (95% CI, 0.978 to 0.996) for cornea scars, 0.997 (95% CI, 0.992 to 1.000) for ocular surface tumours, 0.993 (95% CI, 0.984 to 1.000) for corneal deposits, 1.000 (95% CI, 1.000 to 1.000) for acute angle-closure glaucoma, 0.992 (95% CI, 0.985 to 0.999) for cataracts and 0.993 (95% CI, 0.985 to 1.000) for bullous keratopathy. The triage of referral suggestion using the smartphone images exhibited high performance, in which the sensitivity and specificity were 1.00 (95% CI, 0.478 to 1.00) and 1.00 (95% CI, 0.976 to 1.000) for 'urgent', 0.867 (95% CI, 0.683 to 0.962) and 1.00 (95% CI, 0.971 to 1.000) for 'semi-urgent', 0.853 (95% CI, 0.689 to 0.950) and 0.983 (95% CI, 0.942 to 0.998) for 'routine' and 1.00 (95% CI, 0.958 to 1.00) and 0.896 (95% CI, 0.797 to 0.957) for 'observation', respectively. CONCLUSIONS: The AI system achieved promising performance in the diagnosis of cataracts and corneal diseases.