Yoko Kazato

Pathological Findings of Multifocal Choroiditis with Panuveitis and Punctate Inner Choroidopathy

PurposeTo compare the pathological findings between multifocal choroiditis with panuveitis (MCP) and punctate inner choroidopathy (PIC).MethodsFourteen eyes of 14 patients clinically diagnosed as having MCP or PIC who underwent surgical excision of choroidal neovascularization (CNV) were studied. Immunohistochemical findings of the excised CNV in MCP (eight eyes) and PIC (six eyes) cases were compared. Antibodies against vascular endothelial growth factor (VEGF), CD68, CD3, and CD20 were used as primary antibodies.ResultsExpression of VEGF and CD68 in the CNV was observed in all MCF and PIC cases. In three of eight eyes with MCP, intraocular inflammatory findings were found clinically, while immunohistochemical study demonstrated infiltration of CD20-positive B lymphocytes in the CNV. No B lymphocyte infiltration was found in the six eyes with PIC. No differences in pathological findings were found between the five MCP eyes without intraocular inflammation and the six PIC eyes, with all eyes showing no B lymphocyte infiltration.ConclusionsIn MPC cases showing clinical inflammatory findings, infiltration of B lymphocytes was also observed histopathologically, suggesting that the presence of inflammatory cells in the anterior chamber or vitreous body clinically is an indicator of active inflammatory CNV. However, this study clarifies that MCP eyes without intraocular inflammation and PIC eyes are not different in histopathological findings.

Distribution of Retinal Responses Evoked by Transscleral Electrical Stimulation Detected by Intrinsic Signal Imaging in Macaque Monkeys

PURPOSE The distribution of the electrical current over the retina when electrical pulses are delivered transsclerally has not been clearly determined objectively and quantitatively in humans. The purpose of this study was to determine the pattern of electrically evoked neural activity in the monkey retina by using intrinsic signal imaging. METHODS The intrinsic signals of monkey retinas were recorded as changes in the reflectance of infrared light from the retina after transscleral electrical stimulation by DTL electrodes. The effects of changing the stimulus parameters (e.g., intensity, duration, and frequency) of the electrical current, were investigated. RESULTS Electrical stimulation evoked a uniform change in the reflectivity across the posterior pole of the retina; that is, the intrinsic signals changed uniformly. A peak of the intrinsic signal was not observed at the fovea. The threshold of the intrinsic signal was not significantly different for the macula, perimacula, and optic disc, and the threshold did not differ under dark- and light-adapted conditions. The strength of the signals increased with longer stimulus durations, and the maximum signals were obtained when the stimulus frequency was between 15 and 20 Hz. CONCLUSIONS Intrinsic signals of the monkey retina evoked by transscleral electrical stimulation are elicited uniformly across the posterior pole of the fundus and most likely arise from activation of the inner or middle layers of the retina. These functional measurements could serve as a diagnostic tool for mapping the inner retinal activity, by which the site of a lesion can be noninvasively imaged.

Evaluating Neural Activity of Retinal Ganglion Cells by Flash-Evoked Intrinsic Signal Imaging in Macaque Retina

PURPOSE Intrinsic signal imaging (ISI) detects light-induced microstructural or metabolic changes in retinal tissues. Thus, activities of the rod and cone systems could be mapped topographically. However, no direct evidence indicates the cellular origin of the signals. The purpose of this study was to determine whether and how retinal ganglion cells (RGCs) contribute to ISI. METHODS In anesthetized macaque monkeys, the properties of intrinsic signals were investigated by simultaneous measurement of the retina and the primary visual cortex (V1) with different wavelengths of observation light, measurement of the flash-induced blood flow changes by laser Doppler flowmetry, and intravitreal injection of tetrodotoxin (TTX). RESULTS Slow components of ISI correspond well to the flash-induced blood flow increase. Intrinsic signals of the posterior retina are partially decreased, and the signal of the optic disc is completely abolished by intravitreal injection of TTX at a concentration that should reduce the neural activities of RGCs. The intrinsic signal at the fovea did not change significantly after TTX injection. CONCLUSIONS Photoreceptors in the outer retina and RGCs in the inner retina are major contributors to the intrinsic signals, and the activity of the RGCs can be mapped by using fast and slow components of the signal in the posterior retina. The functional organization of the RGC layer has not been objectively mapped; results presented here indicate that the ISI has the potential to do this.

Origins of retinal intrinsic signals: A series of experiments on retinas of macaque monkeys

Diffuse flash stimuli applied to the ocular fundus evoke light reflectance decreases of the fundus illuminated with infrared observation light. This phenomenon, which is independent of the photopigment bleaching observed as an increase in the reflectance of visible light, is called intrinsic signals. Intrinsic signals, in general, are stimulus-evoked light reflectance changes of neural tissues due to metabolic changes, and they have been extensively investigated in the cerebral cortex. This noninvasive objective technique of functional imaging has good potential as a tool for the early detection of retinal dysfunction. Once the signal properties were studied in detail, however, it became apparent that the intrinsic signals observed in the retina have uniquely interesting properties of their own due to the characteristic layered structure of the retina. Experiments on anesthetized macaque monkeys are reviewed, and the possible origins of the intrinsic signals of the retina are discussed.

Mycobacterium abscessus Corneal Ulcer Following Sutured Clear Corneal Cataract Incision

nodefi ciency or increased susceptibility to infection. Corneal lesion caused by NTM infection is characterized by specifi c spherical infi ltration and growth in the stroma, with a radial spread described as “cracked windshield” and accompanied by satellite lesions. The condition is very rare and often misdiagnosed as keratomycosis, which presents similar corneal fi ndings. According to the Runyon classifi cation, NTM are broadly divided into slow growing and rapidly growing mycobacteria. Infectious keratitis is caused by rapidly growing mycobacteria, that is, M. chelonei, M. fortuitum, M. peregrinum, or M. abscessus, and the fi rst two account for most cases. There is as yet no report of corneal ulcers due to M. abscessus infection caused by sutured clear corneal cataract incision. We report the case of a patient who regained good visual acuity as a result of rapid diagnosis and treatment.

Functional Topography of Rod and Cone Photoreceptors in Macaque Retina Determined by Retinal Densitometry

PURPOSE The purpose of this study is to determine the topography of bleaching in rods, middle/long-wavelength (M/L) and short-wavelength (S) cones in the macaque retina by using a modified retinal densitometry technique. METHODS A modified commercial digital fundus camera system was used to measure continuously the intensity of the light reflectance during bleaching with band pass lights in the ocular fundus of three adult Rhesus monkeys (Macaca mulatta) under general anesthesia. The topography of bleaching in rods, M/L-, and S-cones was obtained separately by considering the characteristic time course of the reflectance changes, depending on the wavelengths of light and retinal locations. RESULTS The distribution of M/L-cones response had a steep peak at the foveal center and was elongated horizontally. The distribution of rod responses was minimum at the foveal center and maximum along a circular region at the eccentricity of the optic disc. The distribution of S-cone responses was highest at the fovea and was excavated centrally. There was a circular region with the maximal responses at 0.38 to 1.0 degrees from the foveal center. CONCLUSIONS With the current imaging technique, not only the steep peak of the M/L-cone responses at the fovea, but the ring-shaped distribution of rod responses in the periphery and the central reduction of S-cone response could be determined with good resolution.

Novel Snapshot Imaging of Photoreceptor Bleaching in Macaque and Human Retinas

PurposeVarious methods have been used to obtain a topographic map of bleached photopigments in human retinas in the past. The purpose of this study was to determine whether the bleaching topography of the photoreceptors could be obtained by snapshot imaging reflectometry.MethodsFour to five fundus photographs of one rhesus monkey and three healthy human subjects were taken by white flashes at intervals of 4 s, with a commercial fundus camera with minimal modifications. The flash-induced reflectance increases (bleaching) were calculated by dividing the reflectance of the first image into the subsequent images, pixel by pixel.ResultsThe topography of the bleached macula corresponded well with the anatomical distribution of the cones. The ratio of reflectance changes in the center to that in the surrounding tissue was high for red and low for green and blue images. These results indicate that the reflectivity changes were not artifacts but were derived from changes in the photopigment density in the cones and rods.ConclusionsThe topography of bleached photoreceptors obtained with a commercial fundus camera from one monkey and three healthy human subjects showed that this technique has potential as a new clinical method for examining photoreceptor function in both normal and diseased retinas.

Immunohistochemical findings of a Bruch’s membrane defect and active choroidal neovascularization in angioid streaks

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