Masamitsu Takeuchi

The second eye of Japanese patients with unilateral exudative age related macular degeneration

AIM To clarify the incidence of choroidal neovascularisation (CNV) and predisposing findings for development of CNV in the second eye of Japanese patients with unilateral exudative age related macular degeneration (AMD). METHODS The second eyes of unilaterally affected patients with exudative (neovascular) AMD treated in our clinic during the past 10 years (1988–97) were carefully followed up for more than a year. Evidence of CNV was confirmed by fluorescein and indocyanine green angiography. Macular lesions in patients, in whom CNV developed in the second eye, were retrospectively evaluated from patient records. RESULTS 170 patients met the criteria. The average follow up period was 47 months (range 12–108 months). All patients were Japanese. CNV developed in the second eye in 12 (7%) of 170 patients, 30.3 months on average after the first examination. Cumulative incidence of developing CNV in the second eye using Kaplan–Meier life table analysis was: 0.6% by 1 year, 5.6% by 3 years, and 12.3% by 5 years, and was relatively low compared with that in white patients. CNV developed most frequently from serous pigment epithelial detachment (PED) in the macula (58%). Soft drusen were not prevalent and risk of developing CNV was not very high (18%). CONCLUSION It was confirmed that there were some differences in the incidence and predisposing findings for CNV developing in AMD among Japanese and other Asian patients compared with those in white people. It is important to recognise these differences between the two populations to understand the pathogenesis and epidemiology of AMD.

Apoptosis of photoreceptor cells in ornithine-induced retinopathy

Abstract • Background: The intravitreal injection of ornithine produces selective damage to the retinal pigment epithelium (RPE) and results in a loss of RPE, choriocapillaris and photoreceptor cells. To elucidate the mechanism of secondary retinal atrophy, we investigated the presence of apoptotic cells in a rat model of ornithine-induced retinopathy. • Methods: At 6 and 12 h and 1, 2, 4, 7, 14 and 28 days after an intravitreal injection of L-ornithine hydrochloride in rat eyes, we removed the eyes and subjected them to histopathological examination. We detected apoptotic cells by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate digoxigenin nick end labeling (TUNEL) assay, which stains the 3′-OH ends of fragmented DNA. We used electron microscopy to detect the apoptotic cells morphologically. • Results: RPE cells were selectively damaged immediately after ornithine administration. TUNEL-positive photoreceptor cells appeared exclusively in the photoreceptor cell layer 12 h after ornithine administration. The number of TUNEL-positive cells increased throughout the 2 days following the injection, then decreased markedly. TUNEL-positive cells remained until 28 days, when the photoreceptor cells had disappeared. The ganglion cell layer, inner nuclear layer and damaged RPE cells were negative for TUNEL staining during all stages. The electron microscopic study also revealed the pyknotic nuclei of apoptotic photoreceptor cells. • Conclusion: An intravitreal injection of ornithine caused primary damage to the RPE, and subsequently some of the photoreceptor cells revealed apoptosis by TUNEL assay. These findings suggest the dysfunction of the RPE causes photoreceptor cell death according to the intrinsic program of an apoptotic mechanism.

Ciliochoroidal detachment following scleral buckling surgery for rhegmatogenous retinal detachment

Purpose and Methods: We observed the peripheral choroid, ciliary body, and depth of the anterior chamber by ultrasound biomicroscopy (UBM) in 31 eyes with rhegmatogenous retinal detachment before and after scleral buckling surgery. Scleral encircling was performed in 11 eyes and segmental scleral buckling in 20 eyes.Results: With UBM, ciliochoroidal detachment was detected in all eyes (100%) following scleral encircling and in 8 eyes (40.0%) following segmental scleral buckling. After scleral encircling procedure, the eyes with preoperatively bullous and wide retinal detachment showed a severe ciliochoroidal detachment and edema of the ciliary body. Shallowing of the anterior camber occurred in all 11 eyes (100%) after scleral encircling and in 12 of 20 eyes (60.0%) after segmental scleral buckling. Marked shallowing with closure of the angle and elevated intraocular pressure occurred in 2 eyes.Conclusion: The results showed that careful postoperative examinations for the anterior segments, chamber angle, and intraocular pressure are necessary with slit-lamp examination and applanation tonometry after scleral buckling surgery.

[Ornithine induced retinopathy in the rat--1. Histopathological study on the retinal pigment epithelium].

An intravitreal injection of a small amount of 1-ornithine hydrochloride damages the retinal pigment epithelium (RPE) selectively in monkey eyes. In this paper, we examined the rat eye and observed similar results. Clinically, retinal edema appeared immediately after injection and showed hyperfluorescence on a fluorescein angiograph after 3 days. Histopathologically, RPE showed marked swelling 3 hours after injection, then became necrotic and disappeared gradually. One month after injection, retinal structure was maintained in the area where RPE regenerated to cover Bruchs membrane, but in the area where RPE cells disappeared, the photoreceptor cells and choriocapillaris degenerated and finally disappeared. In the eyes injected intravitreally with NaCl solution of equivalent osmosis microvacuoles were seen but no necrotic change in RPE. Thus, a small amount of ornithine damaged RPE selectively, and induced disappearance of the photoreceptors and choriocapillaris secondarily.

Selective damage on retinal pigment epithelium causes photoreceptor cell death by apoptosis

The retinal pigment epithelium (RPE) has a major role in maintaining the homeostasis and visual activity of the retina. Various pharmacological agents are known to affect the pigment epithelial cells primarily1,2 or to affect the neurosensory retina and damage the RPE secondarily3–5. When the physiological functions of the pigment epithelium are altered the overlying retina is also affected, resulting in a decrease of visual function.

[Ornithine induced retinopathy in rat--2. Process of disappearance of choriocapillaris].

We observed the process of disappearance of the choriocapillaris after loss of the retinal pigment epithelium (RPE) induced by intravitreal injection or ornithine. Three hours after administration of ornithine, the RPE cells swelled remarkably in the posterior pole, but, the endothelial cells of the choriocapillaris remained intact. At 3 days, the RPE cells became necrotic, but the choriocapillaris still preserved its in normal appearance. At 7 days, RPE disappeared completely in the posterior pole and the choriocapillaris displayed evidence of atrophy; the swollen lumen of the choriocapillaris became narrow the cytoplasm of the endothelium was swollen, and the number of fenestrae was reduced. On the other hand, these changes were not seen where the RPE remained. At 14 days, in the posterior pole, the lumen of the choriocapillaris occluded by the swollen endothelial cells. At 28 days, the choriocapillaris completely disappeared and the large choroidal vessel was directly in contact with Bruchs membrane. These results showed that the RPE is correlated with the presence of the choriocapillaris.