Akiko Okubo

Clinicopathological correlation of polypoidal choroidal vasculopathy revealed by ultrastructural study

Aims: To describe the clinical and histopathological findings in a patient with polypoidal choroidal vasculopathy. Methods: A 76 year old Japanese man had a discrete, orange-red lesion of 1 disc diameter in the macula, with the fluorescein and indocyanine green angiographic and optical coherence tomographic findings compatible with polypoidal choroidal vasculopathy. He underwent a surgical removal of the macular lesion, followed by light and electron microscopic examinations. Results: The histopathological examination revealed that the specimen consisted of degenerated retinal pigment epithelium-Bruch’s membrane-choriocapillaris complex and inner choroid. A tortuous, unusually dilated venule was present adjacent to an arteriole with marked sclerotic changes, appearing to form arteriovenous crossing. These vessels seemed to represent native inner choroidal vessels, and had haemorrhage per diapedesis. Blood cells and fibrin filled the lumina of the vessels and accumulated in the extravascular spaces, indicating vascular stasis. Conclusion: Hyperpermeability and haemorrhage due to stasis of a dilated venule and an arteriole involved by sclerosis at the site where they cross in the inner choroid might cause oedema and degeneration of the tissue. Voluminous accumulation of blood cells and fibrin might generate elevation of tissue pressure sufficient to displace the weakened lesion anteriorly. The result suggests that the polypoidal vessels in this case represent abnormality in the inner choroidal vasculature.

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

High-mobility group box 1 (HMGB1) protein is a multifunctional protein, which is mainly present in the nucleus and is released extracellularly by dying cells and/or activated immune cells. Although extracellular HMGB1 is thought to be a typical danger signal of tissue damage and is implicated in diverse diseases, its relevance to ocular diseases is mostly unknown. To determine whether HMGB1 contributes to the pathogenesis of retinal detachment (RD), which involves photoreceptor degeneration, we investigated the expression and release of HMGB1 both in a retinal cell death induced by excessive oxidative stress in vitro and in a rat model of RD-induced photoreceptor degeneration in vivo. In addition, we assessed the vitreous concentrations of HMGB1 and monocyte chemoattractant protein 1 (MCP-1) in human eyes with RD. We also explored the chemotactic activity of recombinant HMGB1 in a human retinal pigment epithelial (RPE) cell line. The results show that the nuclear HMGB1 in the retinal cell is augmented by death stress and upregulation appears to be required for cell survival, whereas extracellular release of HMGB1 is evident not only in retinal cell death in vitro but also in the rat model of RD in vivo. Furthermore, the vitreous level of HMGB1 is significantly increased and is correlated with that of MCP-1 in human eyes with RD. Recombinant HMGB1 induced RPE cell migration through an extracellular signal-regulated kinase-dependent mechanism in vitro. Our findings suggest that HMGB1 is a crucial nuclear protein and is released as a danger signal of retinal tissue damage. Extracellular HMGB1 might be an important mediator in RD, potentially acting as a chemotactic factor for RPE cell migration that would lead to an ocular pathological wound-healing response.

Age-related maculopathy and sunlight exposure evaluated by objective measurement

Aim: To study the relationship between age-related maculopathy (ARM) and exposure to sunlight using an objective method. Methods: In a case–control study of Japanese men aged ⩾50 years (67 controls without ophthalmic disease and 148 with ARM), those with ARM were separated into groups of early (n = 75) and late (n = 73) ARM. Facial wrinkle length and area of hyperpigmentation, which are considered to be associated with exposure to sun, were measured using imaging with computer-based image analysis. Skin tone was also measured on the upper inner arm, which is not exposed to sun. Early and late ARM association with skin measurements was then evaluated. Results: Significantly more facial wrinkling (p = 0.047, odds ratio 3.8; 95% CI 1.01 to 13.97) and less facial hyperpigmentation (p = 0.035, odds ratio 0.3; 95% CI 0.08 to 0.92) was present in late ARM cases. The relationship between skin tone and ARM risk was not statistically significant. Conclusions: This objective method showed that lifetime exposure to sunlight is an important factor in the progression of late ARM. An individual’s reaction to sunlight exposure may have a role in ARM progression in addition to total lifetime exposure to sunlight.

Responsiveness of eyes with polypoidal choroidal vasculopathy with choroidal hyperpermeability to intravitreal ranibizumab

BackgroundTo determine the role played by vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) based on an interventional immunology theory.MethodsEyes with PCV were divided in a masked fashion into those with choroidal hyperpermeability (HP group) and those with normal choroidal permeability (NP group) based on the indocyanine green angiograms. The inter-rater agreement rate was evaluated using Fleiss’ kappa. Patients were treated by intravitreal ranibizumab (IVB). The central choroidal thickness and central foveal thickness (CFT) at the baseline and 7 days after the treatment were measured by optical coherence tomography.ResultsAmong the 57 consecutive eyes diagnosed with PCV, 42 eyes of 42 patients met the inclusion criteria (21 eyes/HP group vs 21 eyes /NP group). Central choroidal thickness in HP group was significantly thicker than that in the NP group (P < .001, Mann–Whitney U test). The inter-rater agreement was high with a Fleiss’ kappa = 0.95, P < .0001. The percentage reduction in the CFT in HP group (14.0%) was significantly less than that in NP group (20.4%; P = .013, Mann–Whitney U test).ConclusionsEyes with PCV that are associated with choroidal hyper-permeability may not be strongly associated with VEGF-related pathology, and may not respond favorably to anti-VEGF monotherapy.

Plasticity of polypoidal lesions in polypoidal choroidal vasculopathy.

PurposeThe aim of this study was to describe the clinical course in a patient with polypoidal choroidal vasculopathy (PCV).MethodsA 68-year-old man with PCV in the left eye was followed up by means of routine examinations including fluorescein angiography and indocyanine green angiography for over 60 months.ResultsThroughout the follow-up period, the patient experienced repeated lesions in the macula, such as serosanguineous detachment of the retinal pigment epithelium and neurosensory retina, but retained good visual acuity. Indocyanine green angiography disclosed spontaneous regression of polypoidal vessels followed by significant changes in the choroidal circulation: a group of polypoidal structures disappeared, and after several months a small choroidal vessel became apparent that was distant from the previously observed polypoidal structure rather than representing an extension of the original lesion.ConclusionThe clinical observation suggests that in some cases of PCV the choroidal vasculature may be altered with time, in that some vessels in the inner choroid and even the choriocapillaris may close and collateral vessels and/or new vessels may develop to form complex such as that described here.

Predictable signs of benign course of polypoidal choroidal vasculopathy: based upon the long-term observation of non-treated eyes

Purpose:  To find predictable signs of benign polypoidal choroidal vasculopathy (PCV).

Ultracytochemical demonstration of glycogen in cone, but not in rod, photoreceptor cells in the rat retina

The presence of native glycogen in photoreceptor cells of the rat retina has not been identified in the literature. We have studied this ultracytochemically. After perfusion with glutaraldehyde fixative, the eyes were enucleated, and the retinal tissues, postfixed with OsO4, were embedded in epoxy resin. Some tissues were treated with saliva before postfixation. Ultrathin sections, stained by the periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) method or with uranyl acetate and lead citrate, were examined by electron microscopy. On routinely stained sections, glycogen particles seemed to be absent in the cytoplasmic matrix of the photoreceptor cells because they were indistinguishable from the numerous ribosomes. This was due to a similarity in size and electron density. After PA-TCH-SP staining, fine electron-dense reaction products appeared on small cytoplasmic particles (but not on ribosomes) in the inner segments, perikarya and synaptic terminals of a subpopulation of photoreceptor cells. These particles, 15-25 nm in diameter, were identified as beta-particles of glycogen because of their susceptibility to enzyme digestion. The glycogen-rich photoreceptor cells were thought to be cone cells by reasons of their morphological features, such as synaptic terminals, nuclei and outer segments. These results suggest that the cone, but not the rod, photoreceptor cells in the rat contain abundant glycogen.

Intravitreal Triamcinolone Acetonide for Exudative Age-Related Macular Degeneration among Japanese Patients

Aim: To study the results of intravitreal triamcinolone acetonide (TA) for exudative age-related macular degeneration (AMD) among Japanese patients. Methods: 13 eyes of 12 Japanese patients (9 males and 3 females) with subfoveal choroidal neovascularization (CNV) of exudative AMD received intravitreal TA (8 mg). Visual acuity, size of CNV and serous retinal detachment, and complications related to treatment were evaluated for 6 months or longer. Results: Postoperative maximum visual acuity significantly improved (p < 0.05). Postoperative eyes had a greater probability of a reduced size of CNV and/or retinal detachment compared to preoperative eyes. Seven eyes showed increased intraocular pressure (21 mm Hg or over), which was controlled well by medication. Cataract development and advancement were observed in 90% of phakic eyes. No other serious complications were found. Conclusions: Intravitreal TA might be an effective treatment for subfoveal CNV of exudative AMD among Japanese as well as Caucasian patients for a comparatively short period.

Early structural changes during spontaneous closure of idiopathic full-thickness macular hole determined by optical coherence tomography: a case report

BackgroundSpontaneous closure of an idiopathic full-thickness macular hole has been reported to occasionally occur. However, the cells involved in plugging the macular hole have not been determined conclusively. We aimed to report the early structural changes that occur during a spontaneous closure of an idiopathic full-thickness macular hole determined by spectral-domain optical coherence tomography.Case presentationA 71-year-old Japanese man with an idiopathic full-thickness macular hole and subclinical posterior vitreous detachment in the left eye was followed. Three weeks after the identification of the macular hole, optical coherence tomography showed tissue that protruded from the interior wall of the macular hole at the level of the external limiting membrane toward the center of the macular hole. Five months after the first examination, he returned with improvements of his visual symptoms, and the macular hole was closed by a thin retinal tissue which included the restored external limiting membrane that bridged across the macular hole. However, the inner segment/outer segment junction line was not intact and the fovea was detached. Two months later, optical coherence tomography showed an almost normal foveal configuration with an essentially restored inner segment/outer segment junction line and foveal reattachment.ConclusionOur results suggest that Müller cells proliferate and/or extend at the level of the end of the external limiting membrane to form a tissue bridge across the macular hole associated with the external limiting membrane restoration first of all. This leads to the adhesion of other retinal layers and resolution of the foveal detachment.

Hyperreflective dots surrounding the central retinal artery and vein in optic disc melanocytoma revealed by spectral domain optical coherence tomography

PurposeTo report findings of optic disc melanocytoma (ODM) obtained using spectral domain optical coherence tomography (SD OCT), with special reference to the central retinal artery and vein surrounded by hyperreflective dots.MethodsRetrospective review of five eyes of five patients with ODM. Demographic information, ophthalmic examination including best-corrected visual acuity, dilated funduscopic examination, and SD OCT images were evaluated.ResultsDome-shaped, darkly pigmented tumors were seen ophthalmoscopically in the optic discs of all eyes. On OCT, the first branches of the central retinal artery and/or vein were well defined as oblique sections of tubular structures with a perivascular distribution of hyperreflective dots in the elevated retina (nerve fiber layer) over the tumor. The portions where these vessels turn toward the retina were displaced more anteriorly than those of eyes without ODM. Hyperreflective dots of various sizes were also observed in elevated retinas over the tumors, which shadowed and obscured the subjacent tissue in all eyes.ConclusionsSD OCT provides higher definition images of ODM relating to the branches of the central retinal artery/vein, revealing anterior displacement of vessels and perivascular distribution of hyperreflective dots that suggest melanophages and/or tumor cells or proteins and/or lipid deposits.