Satoko Nakagawa

Punctate hyperfluorescent spots associated with central serous chorioretinopathy as seen on indocyanine green angiography.

Purpose: The purpose of this study was to examine indocyanine green angiography of eyes with central serous chorioretinopathy (CSC). Methods: We retrospectively studied the medical records of 39 patients (41 eyes) with active CSC who were <50 years of age. All patients had undergone fluorescein angiography and indocyanine green angiography using a confocal laser scanning system. Results: On indocyanine green angiography, most patients showed choroidal abnormalities, such as filling delay, venous dilation, subretinal leakage, or focal areas of hyperfluorescence, that were attributed to choroidal vascular hyperpermeability. In addition, punctate hyperfluorescent spots were seen in 38 of 41 eyes (93%) with active CSC and in 29 of 37 fellow eyes (78%); these spots were seen in the macular area and outside the vascular arcade or in peripapillary locations, and they often appeared as clusters of distinct spots. A cluster of punctate hyperfluorescent spots was seen on midphase indocyanine green angiography, and focal areas of hyperfluorescence often appeared to expand with time from these punctate hyperfluorescent spots. Conclusion: Focal areas of hyperpermeability in CSC may be derived from the leakage of tiny punctate spots in the inner choroid. Hyperpermeability of these lesions may be involved in the development of serous retinal detachment associated with CSC.

Wide-Field Fundus Autofluorescence Imaging of Retinitis Pigmentosa

PURPOSE To evaluate the clinical usefulness of wide-field fundus autofluorescence (FAF) imaging in patients with retinitis pigmentosa (RP). DESIGN Cross-sectional case series. PARTICIPANTS Seventy-five eyes of 75 patients with RP. METHODS We examined the eyes of the RP patients using the Optos 200Tx imaging system (Optos PLC, Dunfermline, United Kingdom) and identified abnormal FAF patterns such as ring hyperautofluorescence and patchy hypoautofluorescent areas. Patients with hyperautofluorescent rings or foveal hyperautofluorescence were compared with those without such findings. We determined the percentage area occupied by the FAF abnormalities within a defined region of the eye and examined the relationship between the percentage area of these abnormalities and the visual field area. Moreover, we categorized the patients into 3 different groups based on the presence of a patchy hypoautofluorescent lesion larger than 1 disc diameter: Group A consisted of those with patchy lesions smaller than 1 disc diameter, group B consisted of those with patchy lesions larger than 1 disc diameter but present in only 1 quadrant, and group C consisted of those with patchy lesions larger than 1 disc diameter and present in more than 1 quadrant. In addition, various clinical characteristics were compared among these 3 groups. MAIN OUTCOME MEASURES Predicting the visual field size and duration of the disease in RP patients based on FAF patterns. RESULTS Patients without hyperautofluorescent rings or foveal hyperautofluorescence had better visual acuity or mean deviation measured with a Humphrey perimeter. The total area of the abnormal FAF image correlated with the visual field area measured with a Goldmann perimeter (R = -0.64, P<0.001). The individuals with the large patchy hypofluorescent areas (i.e., larger than 1 disc diameter) were older than those with small patchy hypofluorescent areas (group A vs. groups B and C, P = 0.002 and P<0.001, respectively) and had experienced the symptoms for longer durations (group A vs. groups B and C, P<0.05 and P<0.001, respectively). CONCLUSIONS We can estimate the visual field in patients with RP using the objective measurements from wide-field FAF. The presence of patchy hypofluorescent lesions can be used an indicator of the duration of RP. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Granulocyte colony-stimulating factor attenuates oxidative stress-induced apoptosis in vascular endothelial cells and exhibits functional and morphologic protective effect in oxygen-induced retinopathy

Granulocyte colony-stimulating factor (G-CSF) is a known hematopoietic glycoprotein, and recent studies have revealed that G-CSF possesses other interesting properties. Oxidative stress is involved in many diseases, such as atherosclerosis, heart failure, myocardial infarction, Alzheimer disease, and diabetic retinopathy. This study was designed to examine whether G-CSF has a protective effect on endothelial cells against oxidative stress and to investigate whether G-CSF has a therapeutic role in ischemic vascular diseases. Expression of G-CSF (P < .01) and G-CSF receptor (P < .05) mRNA in human retinal endothelial cells (HRECs) was significantly up-regulated by oxidative stress. Treatment with 100 ng/mL G-CSF significantly reduced H(2)O(2)-induced apoptosis in HRECs from 61.7% to 41.4% (P < .05). Akt was phosphorylated in HRECs by G-CSF addition, and LY294002, a PI3K inhibitor, significantly attenuated the antiapoptotic effect of G-CSF (by 44.1%, P < .05). The rescue effect was also observed in human umbilical vein endothelial cells. In mouse oxygen-induced retinopathy model, G-CSF significantly reduced vascular obliteration (P < .01) and neovascular tuft formation (P < .01). G-CSF treatment also clearly rescued the functional and morphologic deterioration of the neural retina. A possibility of a novel therapeutic strategy for ischemic diseases through attenuating vascular regression using G-CSF was proposed.

Knockout of ccr2 alleviates photoreceptor cell death in a model of retinitis pigmentosa.

Neuroinflammation involving CC chemokines such as monocyte chemoattractant protein-1 (MCP-1) has been demonstrated in the pathological process of retinitis pigmentosa (RP), an inherited degenerative retinal disease. However, the mechanism of MCP-1 and its receptor CCR2 involvement in the disease remains unclear. To investigate the role of MCP1/CCR2 in RP pathogenesis, ccr2 mutant RP mice (ccr2(-/-) rd10) were created and analyzed. The expression of MCP-1, RANTES, stromal cell-derived factor (SDF-1), and tumor necrosis factor-α (TNF-α) in the retinas of wild-type, rd10, and ccr2(-/-) rd10 mice was analyzed using quantitative RT-PCR. Photoreceptor apoptosis (TUNEL staining) and the number of microglia (positive for the F4/80 antibody) in the retina were examined. Retinal function was assessed using electroretinograms, and the structure of the whole retina was analyzed from images obtained using optical coherence tomography (OCT) and by histological examination. The expression levels of MCP-1, RANTES, and SDF-1 increased with time in the rd10 mice but not in the wild-type mice. Rearing the mice in the dark prevented degeneration and resulted in thicker photoreceptor layers at each time point. In those mice, the peaks of chemokine expression shifted to a later time with degeneration, suggesting that the expression of these chemokines was induced during the progression of degeneration. Although the difference was not so obvious, the retina in the ccr2(-/-) rd10 mice was consistently and significantly thicker than that in the rd10 (ccr2(+/+) rd10) mice at all time points. Rhodopsin gene expression was also higher in the ccr2(-/-) rd10 mice than in rd10 (ccr2(+/+) rd10) mice, suggesting photoreceptor survival in the former. Retinal function was also better preserved in the ccr2(-/-) rd10 mice than in the rd10 mice. The number of microglia in the retinas of the ccr2(-/-) rd10 mice was significantly lower than that in the retinas of the rd10 mice. Interestingly, the MCP-1 induction that was observed in the retinas of the rd10 mice was diminished in the retinas of the ccr2(-/-) rd10 mice. Our results suggest that the MCP-1/CCR2 system plays a role in retinal degeneration in rd mouse retinas. Retinal MCP-1 expression in the rd mouse retina may be partially controlled by ccr2-positive circulating cells.

Outer retinal circular structures in patients with Bietti crystalline retinopathy

Background Bietti crystalline retinopathy (BCR) is a distinct retinal degenerative disease characterised by retinal degeneration with many yellow–white crystals located mainly at the posterior pole area. Using spectral domain-optical coherence tomography (SD-OCT), the structural change in retina was investigated. Methods Patients diagnosed with BCR (n=12), retinitis pigmentosa (RP, n=292) and cone dystrophy (n=16) were included in this study. The authors mainly examined fundus photographs and SD-OCT, infrared and fundus autofluorescence images of these patients. Results Crystalline deposits were detected in portions of the retinal pigment epithelium that lacked patchy degenerated lesions. SD-OCT revealed that most of the observed crystalline deposits were located adjacent to the inner side of retinal pigment epithelium layer. The change most frequently observed was circular hyper-refractive structures in the outer nuclear layer. Although the structures were considered to be previously reported “tubular formation” or “tubular degeneration”, we determined that many of these circular structures were slices of spherical structures and were typically noted in areas suspected of ongoing active degeneration. Conclusion BCR has characteristic structures in the outer nuclear layer. Although the incidence of the structure varies, it may be characteristic of retinal degeneration and can be found in many retinal degenerative diseases.

Macular Cone Abnormalities in Retinitis Pigmentosa with Preserved Central Vision Using Adaptive Optics Scanning Laser Ophthalmoscopy

Purpose To assess macular photoreceptor abnormalities in eyes with retinitis pigmentosa (RP) with preserved central vision using adaptive optics scanning laser ophthalmoscopy (AO-SLO). Methods Fourteen eyes of 14 patients with RP (best-corrected visual acuity 20/20 or better) and 12 eyes of 12 volunteers underwent a full ophthalmologic examination, fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), and imaging with a prototype AO-SLO system. Cone density and spatial organization of the cone mosaic were assessed using AO-SLO images. Results In 3 eyes with RP and preserved central vision, cones formed a mostly regular mosaic pattern with small patchy dark areas, and in 10 eyes, the cone mosaic patterns were less regular, and large dark regions with missing cones were apparent. Only one eye with RP demonstrated a normal, regular cone mosaic pattern. In eyes with RP, cone density was significantly lower at 0.5 mm and 1.0 mm from the center of the fovea compared to normal eyes (P<0.001 and 0.021, respectively). At 0.5 mm and 1.0 mm from the center of the fovea, a decreased number of cones had 6 neighbors in eyes with RP (P = 0.002 for both). Greater decrease in cone density was related to disruption of the photoreceptor inner segment (IS) ellipsoid band on SD-OCT images (P = 0.044); however, dark regions were seen on AO-SLO even in areas of continuous IS ellipsoid on SD-OCT. Decreased cone density correlated thinner outer nuclear layer (P = 0.029) and thinner inner segment and outer segment thickness (P = 0.011) on SD-OCT. Conclusions Cone density is decreased and the regularity of the cone mosaic spatial arrangement is disrupted in eyes with RP, even when visual acuity and foveal sensitivity are good. AO-SLO imaging is a sensitive quantitative tool for detecting photoreceptor abnormalities in eyes with RP.

Prevalence and spatial distribution of cystoid spaces in retinitis pigmentosa: investigation with spectral domain optical coherence tomography.

Purpose: To investigate the prevalence and spatial distribution of cystoid spaces (CS) in retinitis pigmentosa patients with spectral domain optical coherence tomography. Methods: A total of 529 eyes of 275 patients with retinitis pigmentosa were examined with spectral domain optical coherence tomography. The presence or absence of CS was judged for each eye. Retinal layer and outer retinal status where the CS existed were also investigated. Statistical analysis was performed using 1 eye per 1 patient. Results: Cystoid spaces were present in 119 of 529 eyes (22.5%) of 74 of 275 patients (26.9%). There were no significant differences between the cases with and without CS except for central foveal thickness (P < 0.001). Cystoid spaces were noted in the inner nuclear layer in almost all eyes (98.6%), and outer nuclear layer/outer plexiform layer was also involved in many eyes (27.8%). Cystoid spaces were sometimes seen in ganglion cell layer (6.9%). Cystoid spaces were predominantly (78.9%) distributed in the relatively preserved retina where external limiting membrane was retained. The presence of epiretinal membrane or posterior vitreous adhesion was associated with the presence of CS (P < 0.001) but showed no relationship with the spatial location of CS (P = 1.000). Conclusion: The prevalence of CS in patients with retinitis pigmentosa was 26.9% and contrary to previous reports, most CS were present in inner nuclear layer. In addition, most CS were observed in relatively retained retina, which is compatible to the prevailing notion. Epiretinal membrane or posterior vitreous adhesion was also associated with the development of CS. The distribution of CS in inner and preserved retina may provide insight for the pathogenesis of CS in retinitis pigmentosa.

The time course changes of choroidal neovascularization in angioid streaks.

Purpose: To assess the clinical course of choroidal neovascularization (CNV) in patients with angioid streaks using optical coherence tomography and fluorescein angiography/indocyanine green angiography. Methods: We examined a consecutive series of 88 eyes of 44 patients with angioid streaks using color fundus photography, optical coherence tomography, and fluorescein angiography/indocyanine green angiography. Results: At the initial visit, 33 eyes exhibited no CNV, 2 exhibited polypoidal choroidal vasculopathy, 8 exhibited Type 1 CNV, 32 exhibited active Type 2 CNV, and 13 exhibited a fibrotic scar. In addition to the 2 eyes that exhibited macular polypoidal choroidal vasculopathy at the initial visit, 3 exhibited peripapillary polypoidal lesions, and 2 exhibited polypoidal lesions at the edge of the preexisting Type 2 CNV/fibrosis. During the follow-up, Type 2 CNV developed in 4 eyes on the basis of Type 1 CNV. Visual acuity was worse in eyes with Type 2 CNV and fibrosis than in those with Type 1 CNV, while polypoidal choroidal vasculopathy did not affect the visual acuity. Conclusion: Eyes with angioid streaks can develop any form of CNV including polypoidal choroidal vasculopathy. Considering the worse visual acuity in eyes with Type 2 CNV and fibrosis, patients should be carefully observed so as to treat them promptly when Type 2 CNV occurred beneath the fovea.

Clinical and immunological characterization of paraneoplastic retinopathy.

PURPOSE To report the clinical and immunological characterization of paraneoplastic retinopathy (PR) and to investigate the association between spectral-domain optical coherence tomography (SDOCT) findings and the targets of autoantibodies in PR. METHODS We retrospectively enrolled eight patients (age range, 57-85 years; four men and four women) suspected of having PR. All patients underwent comprehensive ophthalmic examinations, including best-corrected visual acuity (BCVA) measurement, slitlamp examinations, kinetic visual field testing with Goldmann perimetry, electroretinography (ERG), fundus photography, fluorescein angiography, fundus autofluorescence (FAF), SDOCT, and serum sample tests (Western blot analysis and immunohistochemistry [IHC]). RESULTS Three patients had a history of malignant tumors, and four patients were newly diagnosed as having neoplastic tumors (small cell lung carcinoma [SCLC], thymoma, pancreatic neuroendocrine neoplasm, and colon cancer). Another de novo malignancy (SCLC) was detected in a patient with a history of malignancy (bladder cancer and liposarcoma). The BCVA in these patients ranged from hand motion to 1.5. Goldmann perimetry revealed island, ring-shaped, concentric, or central scotoma. All patients showed nonrecordable or reduced amplitude results on ERG. Fluorescein leakage was detected in five patients. Hyperautofluorescence and/or hypoautofluorescence on FAF was detected in six patients. The serum sample tests identified anti-retinal antibodies in all patients. Patients whose serum contained anti-photoreceptor or anti-retinal pigment epithelium antibody on IHC showed damage of the outer retina on SDOCT. CONCLUSIONS In this case series, PR was associated with a variety of neoplasms and autoantibodies. Spectral-domain OCT can be used to characterize morphologic changes, and the changes were associated with the targets of autoantibodies.

Transconjunctival sutureless intrascleral intraocular lens fixation using intrascleral tunnels guided with catheter and 30-gauge needles

We invented a new method for fixing an intraocular lens (IOL) in the scleral tunnel without using a wide conjunctival incision. Modified bent catheter needles were used to penetrate the IOL haptics through the sclerotomy sites. The IOL haptics were inserted into 30-guage (G) scleral tunnels guided by double 30-G needles piercing the sclera. All procedures were performed through the conjunctiva without wide incision. The procedure does not require special forceps, trocars or fibrin glue, only catheter and 30-G needles. The aid of an assistant was not required to support the IOL haptic. The procedures were easily learnt based on our previous method. As with other transconjunctival sutureless surgeries, patients feel less discomfort and the conjunctiva can be conserved for future glaucoma surgery. Complications included two cases of vitreous haemorrhage (16.7%), and one case each of postoperative hypotony, and iris capture (8.3%). Astigmatism induced by intraocular aberration was the same as we reported previously. Our method for fixing the IOL into the scleral tunnel is innovative, less expensive, less invasive and quick. This modified method is a good alternative for fixing IOL haptics into the sclera.