Yi-Ning Chen

Long-term follow-up of initial trabeculectomy with mitomycin C for primary open-angle glaucoma in Japanese patients.

PurposeTo determine the long-term intraocular pressure (IOP) control and postoperative complications after initial trabeculectomy with use of mitomycin C (MMC) in patients with primary open-angle glaucoma (POAG). Patients and MethodsA retrospective review was conducted of a consecutive series of 123 eyes (87 patients) with POAG who underwent initial trabeculectomy with MMC and had at least 4 years of follow-up. All patients underwent standard trabeculectomy with 0.04% MMC applied intraoperatively for 3 minutes. The long-term outcomes (IOP control and bleb leak, long-standing hypotony, bleb-related infections) were analyzed with the Kaplan-Meier life-table method on the basis of three definitions of successful IOP control (defined as IOP <18 mmHg (definition 1), IOP <16 mmHg (definition 2), and IOP decrease of by ≥30% and <21 mmHg (definition 3)). ResultsThe mean follow-up time was 6.8±1.4 (mean±SD) years. The cumulative survival rates were 67.0±4.6%, 44.5±5.4%, and 74.1±4.2%, respectively, based on definitions 1, 2, and 3, 8 years postoperatively by life-table analysis. At 8 years, bleb leak occurred in 7.9±2.6% of eyes, long-standing hypotony in 8.3±2.5%, and bleb-related infections in 5.9±2.4%. ConclusionLong-term outcome after initial trabeculectomy with MMC in Japanese POAG patients is comparable with that reported in other populations and with that after trabeculectomy with 5-fluorouracil.

Morphological changes in the visual pathway induced by experimental glaucoma in Japanese monkeys

Glaucoma, an optic neuropathy, is the leading cause of world blindness. In this condition, the damage extends from the retina to the visual center in the brain, although the primary region of damage is thought to be the optic nerve head (ONH), with the lateral geniculate nucleus (LGN) being secondarily affected. We investigated time-dependent alterations in the ONH, the optic nerve (ON), and the LGN after intraocular pressure (IOP) elevation in Japanese monkeys (a species more similar to humans than other macaque species). Nine Japanese monkeys, each with an experimental glaucomatous left eye, and two naive monkeys were studied. Ocular-testing sessions (including IOP measurement and fundus photography) were held weekly. Eyes and brains were enucleated at 2-48 weeks after IOP elevation, and alterations in ONs and LGN were evaluated. The IOP of the treated eyes was monitored periodically and found to be elevated continuously throughout the observation period in each monkey. The ONH of the glaucomatous eyes exhibited time-dependent deep cupping and thinning of the rim area from 2 weeks after the IOP elevation. Loss of axons and a decrease in the area of ON were first observed at 4 and 28 weeks, respectively. Neuronal loss was first observed at 2 weeks in layers 1 and 2 of LGN [magnocellular (M)-layer] and at 12 weeks in layers 3-6 of LGN [parvocellular (P)-layer]. Neuronal shrinkage was first observed at 2 weeks in all layers in LGN. These findings indicate that in Japanese monkeys, damage to neurons in LGN can be detected in the early phase (first few weeks) after an IOP elevation, as can damage to ONH.

Neuroprotective effect of calcium channel blocker against retinal ganglion cell damage under hypoxia

The purpose of this study was to determine whether iganidipine, nimodipine and lomerizine, potentially useful calcium channel blockers for ophthalmic treatment, have direct retinal neuroprotective effects against hypoxic damage in experimental in vitro model. We used purified retinal ganglion cells (RGCs) from newborn rats. RGCs were incubated in controlled-atmosphere incubator in which oxygen levels were reduced to 5% normal partial pressure and cell viability was assessed. We also examined the effect of calcium channel blockers on the calcium ion concentration in RGC under hypoxic stress by calcium imaging. Iganidipine, nimodipine and lomerizine (0.01-1 microM) increased the RGC viability. Increase in intra-RGC calcium ion concentration by hypoxic damage was reduced by these calcium channel blockers. In conclusion, iganidipine, nimodipine and lomerizine were effective against hypoxic RGC damage in vitro. This neuroprotective effect was thought to be mediated by blocking calcium ion influx into RGC. These findings suggest that iganidipine, nimodipine and lomerizine have a direct neuroprotective effect against RGC damage related to hypoxia.

Imaging Mouse Retinal Ganglion Cells and Their Loss In Vivo by a Fundus Camera in the Normal and Ischemia-Reperfusion Model

PURPOSE To visualize retinal ganglion cells (RGCs) and their gradual loss in the living mouse. METHODS With the use of B6.Cg-Tg(Thy1-CFP)23Jrs/J mice, which express cyan fluorescent protein (CFP) in RGCs, and a commercially available mydriatic retinal camera attached with a 5 million-pixel digital camera to visualize RGCs in vivo, the authors recorded fundus photographs longitudinally in the ischemia reperfusion model group and the untreated group to evaluate longitudinal changes in the number of RGCs in experimental models. Moreover, RGCs expressing CFP were evaluated histologically by a retrograde-labeling method and retinal whole mount or sections. RESULTS The authors devised an in vivo imaging technique using a conventional retinal camera and visualized RGCs at the single-cell level. In the ischemia reperfusion model, a longitudinal reduction in the number of RGCs was demonstrated in each mouse eye. The number of RGCs and the fluorescence intensity of the nerve fiber decreased considerably during the first week. The percentages of RGCs decreased to 34.2% +/- 7.5%, 24.1% +/- 9.1%, 23.0% +/- 9.3%, and 22.2% +/- 8.4% (mean +/- SD, n = 5) of the percentages before injury at 1, 2, 3, and 4 weeks after injury, respectively (P < 0.001). In this transgenic mouse, 97% of CFP-expressing cells were RGCs and 73% of RGCs expressed CFP. CONCLUSIONS This in vivo technique allows noninvasive, repeated, and longitudinal evaluation of RGCs for investigation of retinal neurodegenerative diseases and new therapeutic modalities for them.