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Background Neurotrophic keratopathy (NK) is a rare degenerative corneal disease caused by damage to the trigeminal nerve. We hereby describe a severe case with bilateral corneal perforation due to leprosy (Hansen’s disease)-associated NK. Case presentation An 89-year-old man with a history of leprosy treated 40 years previously in our sanatorium developed bilateral corneal perforation due to NK. He had a history of bilateral persistent epithelial defects and bacterial keratitis. Although epithelialization was obtained with the use of autologous serum eye drops, progressive corneal thinning concomitant with stromalysis led to bilateral perforation. Over one month treatment with topical antibiotics, anti-inflammatory and lubricants resulted in healing of the epithelial defects and corneal perforations. A Cochet-Bonnet esthesiometer demonstrated a total absence of corneal sensation in both eyes. Conclusions The present case indicated the irreversible nerve damage due to leprosy that had been cured 23 years ago, which can progress over the years and cause bilateral corneal perforations.

To identify the factors associated with the surgical outcomes of Baerveldt glaucoma implant (BGI) for open-angle glaucoma (OAG), the medical records of 51 consecutive OAG patients (age, 43–91 years) who underwent BGI were retrospectively reviewed (median follow-up, 21.7 months). Surgical success was defined as the following postoperative intraocular pressures (IOPs, mmHg): (A) 6 ≤ IOP ≤ 21; (B) 6 ≤ IOP ≤ 18; and (C) 6 ≤ IOP ≤ 15 without loss of light perception or additional glaucoma surgery. Univariate analysis showed that age (all criteria), glaucoma type (criterion C), and preoperative IOP (criteria A and B) were the candidate factors (P P = 0.047) and C (P = 0.02), and the postoperative IOP was lower in the older group 1-year post-surgery (P = 0.002). Furthermore, the multivariate Cox proportional hazards model revealed that older age was independently associated with surgical success for criteria B (relative risk [RR], 0.94; P = 0.02) and C (RR, 0.94; P = 0.01). In conclusion, older age is a factor associated with the surgical success of BGI for OAG.

Transforming growth factor-beta 2 (TGF-β2) is highly concentrated in the aqueous humor of primary open-angle glaucoma patients. TGF-β2 causes fibrosis of outflow tissues, such as the trabecular meshwork (TM), and increases intraocular pressure by increasing resistance to aqueous humor outflow. Recently, histone deacetylase (HDAC) activity was investigated in fibrosis in various tissues, revealing that HDAC inhibitors suppress tissue fibrosis. However, the effect of HDAC inhibitors on fibrosis in the eye was not determined. Here, we investigated the effect of suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, on TGF-β2-induced increased resistance to aqueous humor outflow. We found that SAHA suppressed TGF-β2-induced outflow resistance in perfused porcine eyes. Moreover, SAHA cotreatment suppressed TGF-β2-induced ocular hypertension in rabbits. The permeability of monkey TM (MTM) and Schlemm's canal (MSC) cell monolayers was decreased by TGF-β2 treatment. SAHA inhibited the effects of TGF-β2 on the permeability of these cells. TGF-β2 also increased the expression of extracellular matrix proteins (fibronectin and collagen type I or IV) in MTM, MSC, and human TM (HTM) cells, while SAHA inhibited TGF-β2-induced extracellular matrix protein expression in these cells. SAHA also inhibited TGF-β2-induced phosphorylation of Akt and ERK, but did not inhibit Smad2/3 phosphorylation, the canonical pathway of TGF-β signaling. Moreover, SAHA induced the expression of phosphatase and tensin homolog, a PI3K/Akt signaling factor, as well as bone morphogenetic protein 7, an endogenous antagonist of TGF-β. These results imply that SAHA prevents TGF-β2-induced increases in outflow resistance and regulates the non-Smad pathway of TGF-β signaling in TM and MSC cells.

Satoshi Iraha,1–5Yasuhiko Hirami,1,2 Sachiko Ota,1,2 Genshiro A Sunagawa,3 Michiko Mandai,1–3 Hidenobu Tanihara,5 Masayo Takahashi,1–4 Yasuo Kurimoto1,2 1Department of Ophthalmology, Institute of Biomedical Research andInnovation Hospital, 2Department of Ophthalmology, Kobe City Medical Center General Hospital, 3Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, Kobe, 4Application Biology and Regenerative Medicine, Graduate School of Medicine, KyotoUniversity, Kyoto, 5Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan Purpose: The purpose of this study was to examine the efficacy and safety of valproic acid (VPA) use in patients with retinitis pigmentosa (RP).Patients and methods: This was a prospective, interventional, noncomparative case study. In total, 29 eyes from 29 patients with RP whose best-corrected visual acuities (BCVAs) in logarithm of the minimum angle of resolution (logMAR) ranged from 1.0 to 0.16 with visual fields (VFs) of ≤10° (measured using Goldmann perimeter with I4) were recruited. The patients received oral supplementation with 400mg of VPA daily for 6months and were followed for an additional 6months. BCVAs, VFs (measured with the Humphrey field analyzer central 10-2 program), and subjective questionnaires were examined before, during, and after the cessation of VPA supplementation.Results: The changes in BCVA and VF showed statistically significant differences during the internal use of VPA, compared with after cessation (P=0.001). With VPA intake, BCVA in logMAR significantly improved from baseline to 6months (P=0.006). The mean deviation value of the VF significantly improved from baseline to 1month (P=0.001), 3months (P=0.004), and 6months (P=0.004). These efficacies, however, were reversed to the baseline levels after the cessation of VPA intake. There were no significant relations between the mean blood VPA concentrations of each patient and the changes in BCVA and VF. During the internal use of VPA, 15 of 29 patients answered “easier to see”, whereas blurred vision was registered in 21 of 29 patients on cessation. No systemic drug-related adverse events were observed.Conclusion: While in use, oral intake of VPA indicated a short-term benefit to patients with RP. It is necessary to examine the effect of a longer VPA supplementation in a controlled study design. Keywords: retinitis pigmentosa, valproic acid, clinical trial, retina