Yu Sawada

Structure and function of the interphotoreceptor matrix surrounding retinal photoreceptor cells

The interphotoreceptor matrix (IPM) is a highly organized structure with interconnected domains surrounding cone and rod photoreceptor cells and extends throughout the subretinal space. Based on known roles of the extracellular matrix in other tissues, the IPM is thought to have several prominent functions including serving as a receptor for growth factors, regulating retinoid transport, participating in cytoskeletal organization in surrounding cells, and regulation of oxygen and nutrient transport. In addition, a number of studies suggest that the IPM also may play a significant role in the etiology of retinal degenerative disorders. In this review, we describe the present knowledge concerning the structure and function of the IPM under physiological and pathological conditions.

Future Therapies of Wet Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and the prevalence of the disease increases exponentially with every decade after the age of 50 years. While VEGF inhibitors are promising drugs for treating patients with ocular neovascularization, there are limitations to their potential for improving vision in AMD patients. Thus, future therapies are required to have the potential to improve visual outcomes. This paper will summarize the future strategies and therapeutic targets that are aimed at enhancing the efficacy and duration of effect of antiangiogenic strategies.

Lamina Cribrosa Depth Variation Measured by Spectral-Domain Optical Coherence Tomography Within and Between Four Glaucomatous Optic Disc Phenotypes.

PURPOSE To study lamina cribrosa (LC) depth variation measured by spectral-domain optical coherence tomography (SD-OCT) in four glaucomatous optic disc phenotypes. METHODS In this cross-sectional study, 59 normal eyes and 180 open-angle glaucoma (OAG) eyes were grouped into 56 focally injured discs (FI), 30 generalized enlargement of the optic cup discs (GE), 69 myopic glaucomatous discs (MY), and 25 senile sclerotic discs (SS). They were imaged by enhanced depth imaging SD-OCT, obtaining multiple horizontal and vertical optic disc B-scans. Mean and maximum LC depths were measured relative to Bruchs membrane opening (BMO) and the anterior sclera (AS) reference planes. Lamina cribrosa depths were compared between and among the normal and OAG group disc phenotypes. Lamina cribrosa depth differences within groups were examined as well as the overlap between them. RESULTS Mean and maximum LC depths relative to the BMO and AS reference planes were greater in the OAG group than in the normal group (P < 0.0001). Among glaucomatous phenotypes, the GE group had the greatest (P < 0.001) and the SS group had the smallest (P < 0.05) mean and maximum LC depths. There was a wide range of LC depth overlap between the normal and SS groups, and a high proportion of SS eyes had LC depths within the 95% confidence interval of the normal group. CONCLUSIONS The LC was displaced posteriorly in OAG group compared to the normal group. The LC depth was significantly different among four glaucomatous disc phenotypes. The LC depth of the SS group was similar to the normal group.

Risk factors for primary open-angle glaucoma in Japanese subjects attending community health screenings

Background/aims To describe risk factors associated with primary open-angle glaucoma (POAG) in Japanese subjects who participated in community health screenings. Methods Residents of Akita, Japan, participating in a community health checkup were selected to undergo a comprehensive ophthalmic examination. Glaucoma was diagnosed based on optic disk appearance, perimetric results, and other ocular findings. Systemic blood pressure and intraocular pressure were measured and ocular perfusion pressure was calculated. Logistic regression analysis was performed to determine risk factors for POAG patients. Results and conclusion Of the 710 subjects examined, 26 had POAG. The estimated prevalence of POAG was 3.7%. After adjusting for age, the prevalence of POAG was similar to that found in the Tajimi Study of Japanese subjects. Multivariate logistic regression analysis demonstrated that older age (≥60 years, odds ratio [OR]: 3.49), lower diastolic blood pressure (≤58 mmHg, OR: 2.11), higher intraocular pressure (≥19 mmHg, OR: 4.12), and lower ocular perfusion pressure (≤34 mmHg, OR: 5.78) were associated with increased risk of having POAG. These findings may be relevant for identifying high risk groups.

Association of Myopic Optic Disc Deformation with Visual Field Defects in Paired Eyes with Open-Angle Glaucoma: A Cross-Sectional Study

Purpose To examine the association of myopia with the visual field (VF) defects in open-angle glaucoma (OAG) using paired eyes to eliminate the effect of unknown confounding factors that are diverse among individuals. Methods One hundred eighteen eyes of 59 subjects with myopia (spherical equivalent [SE] ≥ -2 diopter [D] and axial length ≥ 24.0 mm) whose intra-ocular pressure between paired eyes was similar and the mean deviation (MD) of the Humphrey VF test differed by more than 6 dB were included. Refractive errors (SE, axial length) and parameters associated with the papillary and parapapillary myopic deformation (tilt ratio, torsion angle, and β-zone parapapillary atrophy [PPA] area without Bruch’s membrane) were measured in each eye. The paired eyes were divided into worse and better eyes according to the MD of the VF, and parameters were compared between them. Further, multiple linear regression analysis was performed to examine the correlation of the difference in various parameters with the MD difference between paired eyes. Results The SE of all eyes was -6.39 ± 2.15 D (mean ± standard deviation) and axial length was 26.42 ± 1.07 mm. MD of the worse and better VF eyes were -13.56 ± 6.65 dB and -4.87 ± 5.32 dB, respectively. Eyes with worse VFs had significantly greater SE, axial length, tilt ratio, and PPA area without Bruch’s membrane than those with better VFs (all P < 0.05). In multiple linear regression analysis, the difference of the MD between paired eyes was significantly correlated with the difference in the tilt ratio and PPA area without Bruch’s membrane. Conclusion The myopic papillary and parapapillary deformations, but not refractive error itself, were related to the worse VF in paired eyes with OAG. This suggests that myopia influences the severity of the glaucomatous VF defects via structural deformation.

Association of Myopic Deformation of Optic Disc with Visual Field Progression in Paired Eyes with Open-Angle Glaucoma.

Purpose The influence of myopia on glaucoma progression remains unknown, possibly because of the multifactorial nature of glaucoma and difficulty in assessing a solo contribution of myopia. The purpose of this study is to investigate the association of myopia with visual field (VF) progression in glaucoma using a paired-eye design to minimize the influence of confounding systemic factors that are diverse among individuals. Methods This retrospective study evaluated 144 eyes of 72 subjects with open-angle glaucoma, with similar intra-ocular pressure between paired eyes, spherical equivalent (SE) ≤ -2 diopter (D), and axial length ≥ 24 mm. Paired eyes with faster and slower VF progression were grouped separately, according to the global VF progression rate assessed by automated pointwise linear regression analysis. The SE, axial length, tilt ratio and torsion angle of optic discs, Bruch’s membrane (BM) opening area, and gamma zone parapapillary atrophy (PPA) width were compared between the two groups. Factors associated with faster VF progression were determined by logistic regression analysis. Results The mean follow-up duration was 8.9 ± 4.4 years. The mean value of SE and axial length were -6.31 ± 1.88 D and 26.05 ± 1.12 mm, respectively. The mean global visual field progression rate was -0.32 ± 0.38 dB/y. Tilt ratio, BM opening area, and gamma zone PPA width were significantly greater in the eyes with faster VF progression than those with slower progression. In multivariate analysis, these factors were significantly associated with faster VF progression (all P < 0.05), while SE and axial length were not associated with it. Conclusion In myopic glaucoma subjects, tilt of the optic disc and temporal shifting and enlargement of the BM opening were associated with faster rate of VF progression between paired eyes. This suggests that myopia influences VF progression in glaucomatous eyes via optic disc deformations rather than via refractive error itself.

Optic nerve head morphology assessed by laser scanning tomography in normal Japanese subjects.

PurposeTo study the optic disc characteristics using the Heidelberg Retina Tomograph (HRT) II in normal Japanese subjects. MethodsA total of 1060 eyes of 530 normal subjects with reliable HRT images, who participated in the community health checkup in the city of Akita, Japan, were included in the study. Optic disc parameters were obtained using the HRT II. Sex, age, height, weight, blood pressure, ocular perfusion pressure, hemoglobin A1c status, intraocular pressure, and disc area with HRT parameters were assessed using correlation and multiple regression analysis. ResultsDisc area and cup area averaged 2.04±0.44 mm2 (mean±standard deviation) and 0.51±0.34 mm2, respectively. There were no significant differences in parameters between right and left eyes. Males had significantly greater cup area, cup volume, cup/disc ratio than females (P<0.001) and smaller rim area and rim volume. Disc area was strongly correlated with all HRT parameters. Age had moderate correlations with several tomographic parameters in multiple regression analysis, whereas blood pressure, ocular perfusion pressure, intraocular pressure, hemoglobin A1c, height, and weight had weak or no correlations. ConclusionsThis study provided a range of normal HRT II optic disc parameters for Japanese subjects. Compared with data from studies on other races, the mean disc area and cup area of Japanese subjects were between that of African Americans and white subjects. Given the significant differences between males and females, a normative database of HRT II variables should be established by sex.

Structural changes in the lacrimal sac epithelium and associated lymphoid tissue during experimental dacryocystitis

Purpose To examine structural changes in the lacrimal sac epithelium and associated lymphoid tissue of rabbits with experimentally induced dacryocystitis. Methods Experimental dacryocystitis was induced by an inoculation of Staphylococcus aureus into the lacrimal sac. The histological changes of the inflamed lacrimal sac epithelium and associated lymphoid tissue were studied by light and electron microscopy. Results After 1 month, numerous inflammatory cells (CD20-positive B lymphocytes, CD3-positive T lymphocytes, IgA-positive plasma cells, and polymorphonuclear leukocytes) infiltrated the lamina propria and the epithelium overlying the diffuse lymphoid tissue. Three months later, the density of the infiltrated leukocytes was markedly decreased. The epithelial lining overlying the diffuse lymphoid tissue became thicker with numerous secretory granules in the supranuclear regions. Conclusion The lacrimal sac epithelium and associated lymphoid tissue play a major role in the defense mechanism during inflammation. Overproduction of secretory granules after bacterial inoculation could enhance the antimicrobial defense.

Optic Disc Margin Anatomic Features in Myopic Eyes with Glaucoma with Spectral-Domain OCT

PURPOSE To investigate optic disc margin anatomic features in myopic eyes with open-angle glaucoma (OAG) using spectral-domain (SD) OCT. DESIGN Cross-sectional study. PARTICIPANTS Two hundred four eyes of 102 participants with OAG and 106 eyes of 53 participants without glaucoma with axial length of 24 mm or more. METHODS Radial SD OCT B-scans centered on the optic discs were acquired in each eye, and the SD OCT data were colocalized with the optic disc stereophotographs. Optic disc margin anatomic features were evaluated as (1) SD OCT structure coinciding with the disc margin identified in the stereophotograph, (2) border tissue configuration, and (3) presence of Bruchs membrane overhang, and their frequency was computed in each clock-hour position. Further, paired eyes of myopic participants with OAG were divided into eyes with better or worse visual field defect (VFD), according to the mean deviation of the Humphrey visual field test, and associated factors were compared. MAIN OUTCOME MEASURES Spectral-domain OCT structures coinciding with the visible optic disc margin in stereophotographs. RESULTS In myopic eyes with OAG, mean axial length was 25.96±1.07 mm and mean deviation was -8.87±7.78 dB. In approximately 90% of the participants, anterior scleral opening (ASO) coincided with the temporal disc margin and Bruchs membrane opening (BMO) with the nasal disc margin. Border tissue configuration was externally oblique in the temporal region and internally oblique in the nasal region of the optic disc. Bruchs membrane overhang was observed in a relatively small percentage of eyes. The same pattern of disc margin anatomic features was observed in the myopic eyes without glaucoma. The myopic optic disc was shaped by the temporal shifting of the BMO from the ASO, and the extent of shifting was expressed as the width of γ zone parapapillary atrophy (PPA). The greater γ zone PPA width was associated significantly with the worse VFD between paired eyes. CONCLUSIONS The myopic eyes with OAG exhibited characteristic optic disc margin anatomic features that was considered to be derived from myopic deformation of the eye. The greater γ zone PPA width may increase susceptibility to the glaucomatous stress.