Yoshitaka Ohnishi

Formation of Drusen in the Human Eye

Light and electron microscopy of drusen formation in the human eye showed yellow-white spots in the fundus with two morphologic patterns: that of typical drusen and a nodular accumulation of cellular components beneath the retinal pigment epithelial cells. By electron microscopy, the progression of drusen formation could be classified into four stages. Stage I showed budding or evagination of retinal pigment epithelial cells into the subpigment epithelial space. This evaginated portion was connected to the retinal pigment epithelial cell cytoplasm and was surrounded by its basement membrane. In Stage II the evaginated portion of the cell was completely separate from the cytoplasm of its parent retinal pigment epithelial cell. In Stage III, the evaginated portion showed degeneration and disintegration. Finally, in Stage IV, an accumulation of vesicular, granular, tubular, and linear material was seen free within the nodular space beneath the retinal pigment epithelial cell.

Histologic Findings and Prognosis of Uveal Malignant Melanoma in Japanese Patients

PURPOSEnTo determine factors of uveal malignant melanoma that would help to predict prognosis in Japanese patients.nnnMETHODSnFrom 1969 to 1994, 23 eyes with uveal malignant melanoma were enucleated from 23 Japanese patients, and 16 of these patients were studied. In the 16 patients, enucleated eyes were evaluated for tumor characteristics, including cell type and microvascular architecture. Patient records were reviewed for follow-up therapy and outcome. Mortality rate was evaluated four years after enucleation.nnnRESULTSnIn Japanese patients with uveal malignant melanoma, the average tumor size was larger (average largest diameter, 11.36 mm; average increase, 6.25 mm) and the average patient age was younger (55.2 years old) than previously reported for white populations. Patients with spindle cell type melanoma tended to have a better prognosis than those with epithelioid cell type (four-year mortality rates: spindle cell type, 0%; mixed cell type, 43%; epithelioid cell type, 66%). Microvascular architecture patterns interpreted as either network or closed loop patterns were associated with a poorer prognosis (network pattern, P = .03; closed loop pattern, P = .005).nnnCONCLUSIONSnThe prognosis for Japanese patients with uveal malignant melanoma is poorer, and epithelioid cell-type melanoma is more common, than has been reported in white populations. Mitotic figures are well correlated with poor prognosis, as are two microvascular patterns, the network pattern and the closed loop pattern.

Capillary Blood Flow Velocity Measurements in Cystoid Macular Edema With the Scanning Laser Ophthalmoscope

Using a scanning laser ophthalmoscope, we calculated the velocity of retinal blood flow in a juxta-foveolar capillary during the course of cystoid macular edema after partial central retinal vein occlusion in a 53-year-old woman. The mean velocity of the fluorescent dots in the macular capillary of the right eye with cystoid macular edema was 1.59 +/- 0.08 mm/sec at the initial examination. Despite the systemic administration of indomethacin (75 mg/day for three weeks), best-corrected visual acuity decreased from 20/30 to 20/70, and the velocity became 0.82 +/- 0.13 mm/sec. Prednisolone (30 mg/day orally for one week) improved the cystoid macular edema, and the velocity was 0.96 +/- 0.06 mm/sec 12 days after initiation of the drug. The velocity gradually improved; one year later it was 1.65 +/- 0.17 mm/sec and visual acuity was 20/22. Velocity in the left eye, which did not have cystoid macular edema, was 2.16 +/- 0.16 mm/sec. Thus, scanning laser ophthalmoscopy proved useful for measuring the velocity of retinal blood flow.

Fluorescein gonioangiography in diabetic neovascularisation.

Fluorescein angiography of the angle with the Goldmann gonioscopy lens was used to examine eyes of 100 Japanese patients with diabetes mellitus. Ocular tension was 21 mmHg or over in 31 of these 100 patients. Gonioscopy revealed angle neovascularisation in the eyes of 30 patients; however, fluorescein gonioangiography showed evidence of angle neovascularisation in 56 of the 100 patients. Angle neovascularisation was first seen 20.3 ± 4.1s after injection of fluorescein dye. Of the newly formed vessels, the branching small vessels showed more prominent leakage than the larger vessels at the root. With progression of the retinopathy, angle neovascularisation became more severe. Following panretinal photocoagulation in 26 of the patients with neovascular glaucoma, angle neovascularisation remarkably regressed in 12 and moderately regressed in 7 patients. Ocular tension became normal in 13 patients. Two of 31 patients with ocular hypertension were considered as cases of primary open-angle glaucoma as there was glaucomatous cupping, visual field defects and no evidence of newly formed vessels in the angle, as observed using fluorescein gonioangiography. Thus, fluorescein gonioangiography may be helpful in the diagnosis and clinical management of neovascular glaucoma.

Cytopathology of early cellular reaction on implant lenses in monkeys A transmission electron microscopic study

We carried out extracapsular lens extraction with the implantation of a modified C-loop posterior chamber lens in eight monkey eyes. The animals were killed after varying survival of up to 14 days. The intraocular lenses (IOLs) were removed and examined by transmission electron microscopy. Three different types of cells, namely, polymorphonuclear leukocytes, macrophages, and multinucleated giant cells, were observed on the surface of the IOLs. A thin, membrane-like structure composed of finely granular material covered the lens surface. These cell components were not attached directly to the lens surface but, rather, were located on the membrane-like structure.

The Histogenesis of Retinoblastoma

: The histogenesis of retinoblastoma has long been a constantly debatable problem since the last century. Rosettes of retinoblastoma have been studied by electron microscopy using 15 eyes as speciments. The evidences suggest that the rosette is at least composed of visual cells and glial (possibly Muller) cells, providing characteristics of the primitive retina. Therefore, it has been concluded that retinoblastoma does not arise from either of the developing neuronal or glial cells, but from the multipotential embryonic retinal cell which is capable of being differentiated into either of these two cellular systems.

Glial-, neuronal- and photoreceptor-specific cell markers in rosettes of retinoblastoma and retinal dysplasia

Previous studies have shown that a rosette formation represents an attempt to form embryonic retinal tissue, primarily rods and cones. To test the theories as to the origin and characteristics of retinoblastoma cells, we compared the characteristics of tumor rosettes with those of dysplastic rosettes seen in retinal dysplasia using the glial, neuronal and photoreceptor markers. Forty-four retinoblastoma and one retinal dysplasia specimens were analyzed by indirect immunohistochemistry, using specific antibodies against glial fibrillary acidic protein, S-100 protein, myelin basic protein, neuron-specific enolase, neurofilament, retinal S-antigen and retinal pigment epithelial antigen. In human retinoblastoma, all the glial, neuronal, retinal pigment epithelial, and photoreceptor cell markers, except for the neurofilament, were present in parts of rosette-forming tumor cells. However, their localization was different for each antigen and it was not clear whether each tumor cell possesses several antigens. These immuno-positive tumor cells were cytologically indistinguishable from other rosette-forming cells at the light microscopic level. In retinal dysplasia, neuron specific enolase and retinal S-antigen were diffusely expressed in the dysplastic rosettes, however, other antigen were not seen in those rosettes. The staining pattern by immunocytochemistry is totally different in tumor rosettes from dysplastic ones. We found varying localizations of different immunoreactivities within tumor rosettes. These results led us to suggest that tumor cells in the rosettes of retinoblastoma may have the ability to differentiate into neural and glial cells. To prove the theory that retinoblastoma cells may have originated from a primitive neuroectodermal cell capable of multipotentiality, further investigation is needed.

Effects of pilocarpine and paracentesis on occluding junctions between the nonpigmented ciliary epithelial cells

The occluding junctions between the nonpigmented ciliary epithelial cells in the Rhesus monkey have been studied with the electron microscope using horseradish peroxidase as a tracer and the freeze-fracture technique. These junctions can be divided into two distinct classes: one type is made of parallel strands, while the other type consists of a net-like meshwork of junctional strands. The occluding junctions in the pars planar and the valley of the ciliary process are mainly of the parallel type which is composed of between three and 15 strands. After pilocarpine instillation, the straight and parallel strands in these portions became wavy but remained intact. This finding suggests that during accomodation the blood-aqueous barrier is maintained by changing the shape of the occulding junctions so as to resist the contraction of the ciliary muscle. The second type of junctional strands, made up of from five to 18 ridges and grooves, is mainly seen in the crest of the ciliary process. Following repeated paracentesis, every ciliary process of almost all the experimental monkeys developed cysts in the ciliary processes but only at their most anterior portion. The cyst walls were ruptured at several locations. The cysts, the intercellular spaces and the posterior chamber contained fibrin. In freeze-fractured replicas of these specimens, the occluding junctions at the anteriormost portion of the pars plicata were normally composed of from one to five strands of the parallel type, and which were often fragmented after paracentesis. This observation indicates that the occluding junctions in this portion of the ciliary process may be responsible for the leakage of the serum protein into the posterior chamber that is observed after paracentesis.

Cellular reaction on the surface of intraocular lenses removed from human eyes

ABSTRACT We studied four angle‐supported anterior chamber lenses whose optics and haptics were made of poly(methyl methacrylate). All four lenses had been removed from human eyes because of bullous keratopathy. Using light and electron microscopy, we compared the cellular reaction on the optics, which had been in the anterior chamber, with that on the haptics, which had been in touch with the iris stroma. A typical foreign body granuloma was seen around the haptics, while the optics were free of foreign body reaction.

The origin of amyloid in gelatinous drop-like corneal dystrophy

The origin of amyloid in gelatinous drop-like corneal dystrophy, one of the primary corneal amyloidoses, was studied by light and electron microscopy. Milky-white granules over the corneal surface are the first clinical findings. In the initial stage, the amyloid substance exists between the basal cell of the corneal epithelium and the basal lamina of the cell. The basal lamina, Bowmans membrane and the stroma remained intact. Numerous filaments, about 7nm in width, were seen in the normal basal cells. In addition, many fibrils, about 10nm in width, were observed in the damaged basal cells. With progressing of the disease, the amyloid increased in amount and Bowmans membrane disappeared. Our results suggest that the basal cell of the corneal epithelium may produce and secreted the amyloid substance and gelatinous drop-like corneal dystrophy occurred.