Kyoko Ohno-Matsui

International Photographic Classification and Grading System for Myopic Maculopathy

PURPOSEnTo develop a classification and grading system for myopic maculopathy.nnnDESIGNnDevelopment and evaluation of a classification system for myopic maculopathy based on observational case series.nnnMETHODSnA comprehensive set of myopic macular lesions was defined via literature review and through consensus meetings among retinal specialists and clinician scientists. A classification of myopic maculopathy was formulated based on fundus photographs and a modified Delphi process and consensus. Inter- and intraobserver reproducibility, assessed as agreement (%) and weighted kappa values, were evaluated. One hundred retinal photographs with myopia and myopic macular lesions were selected from case series at the High Myopia Clinic of the Tokyo Medical and Dental University, Tokyo, Japan.nnnRESULTSnWe defined 5 categories of myopic maculopathy including no myopic retinal degenerative lesion (Category 0), tessellated fundus (Category 1), diffuse chorioretinal atrophy (Category 2), patchy chorioretinal atrophy (Category 3), and macular atrophy (Category 4). Three additional features to supplement these categories were defined as plus lesions, namely, lacquer cracks, myopic choroidal neovascularization, and Fuchs spot. Posterior staphyloma was considered as a further, important sign of myopic retinopathy. The intraobserver agreement was ≥85% and the corresponding weighted kappa statistic was ≥0.6 between observations. After a brief training session, interobserver kappa statistics reached the predefined satisfactory level (≥0.4), considered as above moderate agreement.nnnCONCLUSIONSnWe propose a classification system for myopic maculopathy that was found to be reproducible. Applying a uniform classification in different studies will facilitate communication and comparison of findings from clinical trials and epidemiologic studies.

Current and predicted demographics of high myopia and an update of its associated pathological changes

Excessive axial elongation of the eye in high myopia can cause biomechanical stretching leading to various ocular complications. The purpose of this review is to provide an update on various pathologic changes, especially in the chorio‐retina and sclera that have been reported recently using advanced ophthalmic bio‐imaging modalities such as optical coherence tomography, magnetic resonance imaging and fundus photography.

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axial length (rs10453441, Pmeta=3.9 × 10(-13)) and corneal curvature (Pmeta=2.9 × 10(-40)) and confirm the previously reported association between GJD2 and myopia. WNT7B significantly associates with extreme myopia in a case-control study with 1,478 Asian patients and 4,689 controls (odds ratio (OR)meta=1.13, Pmeta=0.011). We also find in a mouse model of myopia downregulation of WNT7B expression in the cornea and upregulation in the retina, suggesting its possible role in the development of myopia.

Retinal pigment epithelium cell density in relationship to axial length in human eyes.

To assess associations between axial length and density of retinal pigment epithelium (RPE) cells in various ocular regions.

Glaucomatous-Type Optic Discs in High Myopia

Purpose To assess the prevalence of glaucoma in patients with high myopia defined as myopic refractive error of >-8 diopters or axial length ≥26.5 mm. Methods The hospital-based observational study included 172 patients (336 eyes) with a mean age of 61.9±12.3 years and mean axial length of 30.1±2.3 mm (range: 24.7–39.1mm). Glaucomatous-type optic discs were defined by glaucomatous optic disc appearance. Glaucoma was defined by glaucomatous optic disc appearance and glaucomatous Goldmann visual field defects not corresponding with myopic macular changes. Results Larger disc area (mean: 3.18±1.94 mm2) was associated with longer axial length (P<0.001; standardized correlation coefficient: 0.45). Glaucoma was detected in 94 (28%; 95% Confidence intervals: 23%, 33%) eyes. In multivariate analysis, glaucoma prevalence was 3.2 times higher (P<0.001) in megalodiscs (>3.79 mm2) than in normal-sized discs or small discs (<1.51 mm2) after adjusting for older age. Axial length was not significantly (P = 0.38) associated with glaucoma prevalence in that model. Glaucoma prevalence increased by a factor of 1.39 for each increase in optic disc area by one mm2. Again, axial length was not significantly (P = 0.38) associated with glaucoma prevalence when added to this multivariate model. Conclusion Within highly myopic individuals, glaucoma prevalence increased with larger optic disc size beyond a disc area of 3.8 mm2. Highly myopic megalodiscs as compared to normal sized discs or small discs had a 3.2 times higher risk for glaucomatous optic nerve neuropathy. The increased glaucoma prevalence in axial high myopia was primarily associated with axial myopia associated disc enlargement and not with axial elongation itself.

Peripapillary Diffuse Chorioretinal Atrophy in Children as a Sign of Eventual Pathologic Myopia in Adults

PURPOSEnTo search for a morphologic biomarker to differentiate between pathologic myopia and simple childhood myopia.nnnDESIGNnRetrospective case series.nnnPARTICIPANTSnThe study included children (age ≤15 years) with high myopia (as defined by the Japanese Ministry of Health and Welfare) who attended the High Myopia Clinic between April 1982 and March 1994, had undergone fundus photography, and had a follow-up of 20 years or more.nnnMETHODSnFundus photographs obtained in childhood and adulthood were examined for presence of pathologic myopia, defined by high myopia (myopic refractive error >8 diopters or axial length ≥26.5 mm) and the presence of stage 2 or higher myopic maculopathy.nnnMAIN OUTCOME MEASURESnMyopic maculopathy in childhood.nnnRESULTSnThe study included 56 eyes of 29 patients with a mean age of 10.2±3.6 years at the initial visit and an age of 36.0±7.6 years at the last visit. Mean axial length was 27.0±1.4 mm at baseline and 29.7±2.0 mm at the last visit. At the last visit, 19 eyes (34%) had tessellated fundus alone, 31 eyes (55%) had diffuse chorioretinal atrophy, 3 eyes (5%) showed patchy chorioretinal atrophy, and 1 eye (2%) had macular atrophy. Thus, 35 eyes (63%) had pathologic myopia in adulthood. Among the 35 eyes, 29 (83%) already had diffuse chorioretinal atrophy at the initial visit in childhood and the remaining 6 eyes (17%) showed tessellated fundus in childhood. The diffuse chorioretinal atrophy seen in childhood was restricted to the area temporal to the peripapillary region.nnnCONCLUSIONSnThe presence of peripapillary diffuse chorioretinal atrophy in children with high axial myopia may be an indicator for the eventual development of advanced myopic chorioretinal atrophy in later life. These features in children may be helpful for differentiating simple childhood myopia from eventual pathologic myopia.

Extreme Thinning or Loss of Inner Neural Retina Along the Staphyloma Edge in Eyes With Pathologic Myopia

PURPOSEnTo investigate the morphologic changes along the edge of posterior staphyloma in highly myopic eyes with patchy chorioretinal atrophy and to identify the relationship between retinal thinning and the visual field (VF) defects found in these eyes.nnnDESIGNnRetrospective, observational case series.nnnMETHODSnTwenty eyes (17 patients) with pathologic myopia (myopic refractive error ≥ 8 diopters or an axial length ≥ 26.5xa0mm) and patchy atrophy along the staphyloma edge were analyzed retrospectively. The VFs were obtained by Goldmann kinetic perimetry.nnnRESULTSnIn the area of patchy atrophy, the inner retinal tissue was very thin or completely absent. Any remnants of the retinal tissue appeared to be adherent to the layer of large choroidal vessels or to the sclera. The mean thickness of the retina at its thinnest point in the area was 51.6 ± 29.0xa0μm in 20 eyes. The retina was thinner than 50xa0μm at its thinnest point in 12 (60.0%) of the 20 eyes, and the mean retinal thickness at its thinnest point in these 12 eyes was 32.1 ± 16.0xa0μm (range, 4 to 49xa0μm). Nineteen eyes (VF of 1 eye was not determined) had very similar VF findings by Goldmann perimetry, that is, a defect of the sector corresponding to the course of retinal nerve fiber over the patchy atrophy.nnnCONCLUSIONSnThe results show that the thickness of not only the outer retina, but also of most of the inner retina, including the nerve fiber layer, is significantly thinner at the staphyloma edge. Such damage to the inner retina along the staphyloma edge causes the VF defects in highly myopic eyes.

FEATURES OF POSTERIOR STAPHYLOMAS ANALYZED IN WIDE-FIELD FUNDUS IMAGES IN PATIENTS WITH UNILATERAL AND BILATERAL PATHOLOGIC MYOPIA.

Purpose: Pigmentary alterations along the presumed edge of staphyloma in wide-field fundus images have been reported to be highly correlated with the eye shape in three-dimensional magnetic resonance images. The purpose of this study was to analyze Optos images in a large series of highly myopic patients to determine the prevalence, types, and features of staphylomas. Methods: One thousand and sixty eyes of 541 patients with high myopia (axial length ≥ 26.5 mm) in at least one eye were retrospectively analyzed in Japan and Spain. To determine the presence and types of staphyloma, the authors focused on pigmentary abnormalities along the presumed edge of staphylomas with at least one positive finding in fundus images, autofluorescent images, and infrared images by Optos. Results: Posterior staphyloma was detected in 552 of 1,060 eyes (55%) in Optos images. Wide macular type was the most common (79%), followed by narrow macular (15%), then peripapillary (3%), inferior, and finally nasal. In the 60 non-highly myopic eyes of patients with unilateral high myopia, staphyloma was detected in 40%, suggesting that unilateral high myopia might be a bilateral disorder with marked differences in the degree of staphyloma between the two eyes. Combined staphylomas such as the peripapillary type within the wide macular type were also found. Conclusion: Posterior staphyloma was found in 55% of 1,060 eyes with bilateral or unilateral pathologic myopia. Wide macular was the most common type, although there were much more variations in the shape of staphylomas than that had been previously believed.

Glaucoma in high myopia and parapapillary delta zone

Purpose To examine the prevalence of glaucomatous optic neuropathy (GON) in a medium myopic to highly myopic group of patients and its association with parapapillary gamma zone and parapapillary delta zone. Methods The retrospective observational hospital-based study included patients who had attended the Tokyo High Myopia Clinics within January 2012 and December 2012 and for whom fundus photographs were available. GON was defined based on the appearance of the optic nerve head on the fundus photographs. Results The study included 519 eyes (262 individuals) with a mean age of 62.0±14.3 years (range:13–89 years) and mean axial length of 29.5±2.2 mm (range:23.2–35.3mm). GON was present in 141 (27.2%; 95% confidence intervals (CI): 23.3, 31.0%) eyes. Prevalence of GON increased from 12.2% (1.7, 22.7) in eyes with an axial length of <26.5mm to 28.5% (24.4, 32.5) in eyes with an axial length of ≥26.5mm, to 32.6% (27.9, 37.2) in eyes with an axial length of ≥28mm, to 36.0% (30.5, 41.4) in eyes with an axial length of ≥29mm, and GON prevalence increased to 42.1% (35.5, 48.8) in eyes with an axial length of ≥30mm. In multivariate analysis, higher GON prevalence was associated (Nagelkerke r2: 0.28) with larger parapapillary delta zone diameter (P<0.001; odds ratio (OR):1.86;95%CI:1.33,2.61), longer axial length (P<0.001;OR:1.45;95%CI:1.26,1.67) and older age (P = 0.01;OR:1.03;95%CI:1.01,1.05). If parapapillary delta zone width was replaced by the vertical disc diameter, higher GON prevalence was associated (r2:0.24) with larger vertical optic disc diameter (P = 0.04;OR:1.70;95%CI:1.03,2.81), after adjusting for longer axial length (P<0.001;OR:1.44;95%CI:1.26,1.64) and older age (P<0.001;OR:1.04;95%CI:1.02,1.06). Conclusions Axial elongation associated increase in GON prevalence (mean: 28.1% in a medium to highly myopic study population) was associated with parapapillary delta zone as surrogate for an elongated peripapillary scleral flange and with larger optic disc size.

Optic Nerve Head Histopathology in High Axial Myopia

Purpose: To describe particularities of the optic nerve head of axially highly myopic eyes. Methods: Measurements were obtained from enucleated globes and from population-based studies. Results: Morphologic optic disc particularities in high axial myopia included enlarged disc size (secondary macrodisc), widening and temporal translocation of the papillary Bruch’s membrane (BM) opening, parapapillary gamma and delta zone, elongation and thinning of lamina cribrosa and peripapillary scleral flange, steeper translamina cribrosa pressure gradient, decreased peripapillary choroid thickness, longer distance between peripapillary arterial circle and optic disc, optic cup flattening, presumably a stretching of the lamina cribrosa pores, and peripapillary intrachoroidal cavitations. These changes may be explained by growth of new BM in the retroequatorial region in the process of emmetropization or myopization as “overshooting” of the emmetropization process. Conclusions: The intrapapillary and parapapillary changes in the highly myopic optic nerve head may be reason for the increased susceptibility for glaucomatous optic nerve damage in high axial myopia. The widening of the papillary BM opening and the potential shift of the optic nerve head’s 3 layer into temporal direction, both potentially leading to the development of parapapillary gamma zone may be of interest for elucidating the process of emmetropization/myopization.