Tsuyoshi Agawa

Profile of intraocular immune mediators in patients with age-related macular degeneration and the effect of intravitreal bevacizumab injection.

Purpose: To measure intraocular cytokine levels in patients with exudative age-related macular degeneration and analyze changes in the cytokine profile 2 days after intravitreal bevacizumab injection. Methods: This prospective case–control study enrolled 37 patients (37 eyes) with age-related macular degeneration including polypoidal choroidal vasculopathy. Twenty-eight age-matched patients (28 eyes) who underwent cataract surgery were used as controls. Undiluted aqueous humor samples were collected after intravitreal bevacizumab injection. Two days after intravitreal bevacizumab injection, cataract surgery was performed and undiluted aqueous humor samples were collected at the beginning of surgery (10 eyes). Twenty-three cytokines were measured using flow cytometry. P values were corrected in multiple comparisons using the conservative Bonferroni–Holm method. The level of significance was set at 0.0022 (0.05/23). Results: At baseline, aqueous humor levels of vascular endothelial growth factor, angiogenin, interferon gamma-inducible protein (IP)-10, macrophage inflammatory protein (MIP)-1&bgr;, monokine induced by interferon &ggr; (Mig), and monocyte chemotactic protein (MCP)-1 were significantly higher in the age-related macular degeneration group than in the control group (P < 0.0022). The result of exploratory multivariate analysis showed that elevated angiogenin level was an important factor that discriminates the two groups (P = 0.0004). Two days after intravitreal bevacizumab injection, vascular endothelial growth factor levels tended to be reduced (P = 0.049), whereas interleukin (IL)-6 and IL-8 levels increased significantly (P < 0.0022). Conclusion: Vascular endothelial growth factor and also angiogenin, IP-10, MCP-1, MIP-1&bgr;, and Mig may be related to the pathogenesis of age-related macular degeneration. Intravitreal bevacizumab injection increases inflammatory cytokine levels, suggesting the induction of an inflammatory process.

Correlation between high-resolution optical coherence tomography (OCT) images and histopathology in an iodoacetic acid-induced model of retinal degeneration in rabbits

Background Recent research on macular disease has prompted investigation into the condition of the intersection of the inner and outer segments (IS/OS) and its relationship with retinal photoreceptor abnormalities. Because the relationship between optical coherence tomography (OCT) images and histopathology is unclear, we compared these in an iodoacetic acid (IAA)-induced model of photoreceptor degeneration in rabbits. Methods IAA (20 mg/kg), which is toxic to photoreceptors, was injected into six coloured rabbits. After IAA administration, nine retinas were used for histopathological study: three from rabbits surviving for 1 day and six from rabbits surviving for 4 months. Four healthy rabbit retinas served as controls. OCT images were taken before euthanasia. Results In the controls, OCT images revealed the IS/OS as a clear, straight line. In rabbits surviving for 1 day, the structure of the photoreceptor IS/OS was destroyed and the IS/OS boundary was not visible. In rabbits surviving for 4 months, the IS was still preserved, but the structure of the OS was destroyed or partially disorganised, and the IS/OS was observed as a wavy, broken line on the OCT images. Conclusion The IS/OS on the OCT images reflected the histopathology of the inner and outer segments in a photoreceptor degeneration model.

Biological activity is the likely origin of the intersection between the photoreceptor inner and outer segments of the rat retina as determined by optical coherence tomography

Background Recent research on macular diseases has prompted investigations into the condition of the intersection between the photoreceptor inner and outer segments (IS/OS) and the relationship with retinal photoreceptor abnormalities. Although the origin of the IS/OS in optical coherence tomography (OCT) images is unclear, it may be related to either the cellular activity of the photoreceptors or the structure of the OS disks. To address this question, we compared the IS/OS status in OCT images of rat retinas before and after euthanasia. Methods OCT images were taken before and after euthanasia in four eyes of two Brown Norway rats. After the OCT images were taken, the rats were used for histopathological studies to confirm that retinal structures were intact. Results Before euthanasia, the IS/OS and external limiting membrane (ELM) line were clearly identifiable on the OCT images. However, after euthanasia, neither the IS/OS nor the ELM line was evident in three out of four eyes, and a faint IS/OS and an ELM line were identified in one eye. Histopathological analysis did not show any abnormalities in the retina in any of the four eyes. Conclusion The origin of the IS/OS identified in OCT images is likely related to the biological activities of the photoreceptor cells.

Correlation between high-resolution optical coherence tomography (OCT) images and histopathology in an N-methyl-N-nitrosourea-induced retinal degeneration rat model.

Background Recent research on macular diseases has prompted investigations into the condition of the intersection between the inner and outer segments (IS/OS), and its relationship with retinal photoreceptor abnormalities. Because the correlation between optical coherence tomography (OCT) images and histopathology is unclear, the authors compared them in an N-methyl-N-nitrosourea (MNU)-induced photoreceptor degeneration rat model. Methods MNU (60 mg/kg), which is toxic to photoreceptors, was injected in 12 Brown Norway rats. After MNU administration, three rats were used per histopathological study 3 h, 6 h, 24 h and 1 week after the injections. Two healthy rats served as controls. OCT images were taken before euthanisation. Results 3 h after the MNU injections, the IS and OS were oedematous, but the IS/OS borderline was recognised histopathologically, and the IS/OS was depicted on the OCT images. Six hours after injections, the OS were preserved, but the IS structures were destroyed or partially disorganised histopathologically, and the IS/OS was not observed on the OCT images. Twenty-four hours after the injections, the IS and OS were totally disorganised histopathologically, and the IS/OS was not depicted on the OCT images. Conclusion The IS structure might be the origin of the IS/OS on OCT images.

Successful closure of large blunt macular chorioretinal rupture: a case report

The authors present a rare case of large chorioretinal rupture caused by blunt traumatic injury of the globe. A 22-year-old woman sustained a blunt injury to her left eye. The best-corrected Snellen visual acuity was 2/20 in her left eye, and hyphema and vitreous hemorrhage were noted. The day after the injury occurred the vitreous hemorrhage had disappeared. Fundus examination revealed a crescent-shaped retinal rupture three disc diameters in size near the macula, and a choroidal rupture six disc diameters in size that was over the vascular arcade. Three days after the injury, vitrectomy with internal limiting membrane peeling was performed. Postoperative prone positioning was maintained for 4 days. Five days postoperatively, closure of the ruptured retina was confirmed. The visual acuity improved to 16/20 4 months after surgery and this was maintained over a 48-month period. In conclusion, early vitrectomy with internal limiting membrane peeling after injury was effective for a case involving severe blunt chorioretinal rupture with closed globe injury.

Aqueous immune mediators in malignant uveal melanomas in comparison to benign pigmented intraocular tumors.

BackgroundTo examine the usefulness of measuring immune mediators in aqueous humor samples for differentiating malignant uveal melanoma from benign pigmented intraocular tumors.MethodsThirteen eyes of 13 patients with uveal melanoma were studied, and 13 eyes of 13 patients with benign pigmented intraocular tumors served as controls. Undiluted samples of aqueous humor were collected, and a cytometric bead array was used to determine the aqueous humor concentrations of 35 immune mediators comprising 14 interleukins (IL), interferon-γ, interferon-γ-inducible protein-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated on activation normal T cell expressed and secreted, monokine induced by interferon-γ, basic fibroblast growth factor, Fas ligand, granzyme A, granzyme B, eotaxin, interferon-inducible T-cell alpha chemoattractant, fractalkine, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, vascular endothelial growth factor, angiogenin, tumor necrosis factor-α, lymphotoxin-α, and CD40L.ResultsAqueous humor levels of angiogenin, IL-8, and MCP-1 were significantly higher in eyes with malignant melanoma than in those with benign tumors (p < 0.05).ConclusionsAngiogenin, IL-8, and MCP-1 levels in aqueous humor may be potential markers for distinguishing malignant uveal melanoma from benign pigmented intraocular tumors, and may be a useful adjunct to histomorphology, diagnostic imaging, and other biomarkers for the diagnosis and appropriate clinical management of malignant uveal melanoma.