Heritability of the morphology of optic nerve head and surrounding structures: The Healthy Twin Study

Abstract

Background: Optic nerve head (ONH) and surrounding structures such as β-zone peripapillary atrophy (PPA) are important structures in glaucomatous pathogenesis. Thus, for understanding genetic components in glaucoma pathogenesis, it is necessary to evaluate the heritability of ONH and surrounding structures. The present study investigated the genetic influences on ONH and surrounding structures such as β-zone PPA and retinal vessels.

Methods: A total of 1,205 adult twins and their family members (362 monozygotic (MZ) twin subjects (181 pairs), 64 dizygotic (DZ) twin subjects (32 pairs), and 779 singletons from 261 families), were part of the Korean Healthy Twin Study. ONH parameters including the vertical cup-to-disc ratio, the presence, the area and the location of β-zone PPA and the angular location of retinal vein were measured. The genetic influences on the structures were evaluated using variance-component methods.

Results: The intraclass correlation coefficient (ICC) values of axial length were highest among the parameters. The ICCs of the area and location of PPA were similar to those of vertical cup-to-disc ratio. However, retinal vessel angular locations showed low ICC values even in MZ twins. After age and sex adjustment, for axial length, vertical cup-to-disc ratio, the presence, area and location of PPA, the estimated narrow-sense heritability was 0.85, 0.48, 0.76, 0.50 and 0.65 in the right eye and 0.84, 0.47, 0.72, 0.46 and 0.72 in the left eye, respectively. The estimated narrow-sense heritability of angular location of the superior and inferior vein was 0.17 and 0.12 in the right eye and 0.13 and 0.05 in the left eye, respectively.

Conclusions: ONH and surrounding structures such as vertical cup-to-disc ratio and the presence, the area and the location of β-zone PPA seemed to be determined by the substantial genetic influence, whereas the venous angular location did not.

Fig 1. Parameter measurements in the present study.

(A) Fovea-to-disc center distance connected the foveal center and optic disc center and was defined as the reference value (white line). The β-zone PPA was defined as the region of chorioretinal atrophy containing both visible sclera and choroidal vessels adjacent to the optic disc (dotted white line). Disc area was defined as the region in the inner margin of scleral ring around optic disc. PPA-to-disc area ratio was used as the modified PPA area in order to compensate for the magnification effect due to AL. The location of β-zone PPA was defined as the angle of the point of maximal radial extent from the reference line (yellow line). The point of maximum radial extent was the point on the temporal β-zone PPA margin where the radial extent of the β-zone PPA was maximal (yellow arrow). (B) The vein angular location was defined as the angle between the fovea-to-disc center (reference) and the largest temporal vein. To define the location of the vein, a circle with a radius half the distance of the fovea-to-disc center was drawn (dotted white line). The point at which the circle meets the vein was regarded as the location of vein (each end of the superior and inferior white lines). The angle between the location of superior vein and the reference was defined as the angular location of the superior vein (angle α). The angle between the location of the inferior vein and the reference was defined as the angular location of the inferior vein (angle β). The ratio of the superior vein angle and the inferior vein angle was defined as the vein angular location ratio.

Fig 2. Classification of the location of β-zone PPA.

(A) When the location of β-zone PPA was greater than 15 degrees superior, it was classified as superior. (B) When the location of β-zone PPA was less than 15 degrees, it was classified as temporal. (C) When the location of β-zone PPA was greater than 15 degrees inferior, it was classified as inferior. (D) When the β-zone PPA was located circumferentially, it was regarded as circumferential.

Fig 3. Correlations between axial length (AL) and peripapillary atrophy (PPA)-to-disc ratio and angular location of retinal vein.

(A), (B) Positively linear correlations were shown between AL and PPA-to-disc ratio. (C-F) Negatively linear correlations were shown between AL and angular locations of retinal vessels, but the correlations seemed weak.

Fig 4. Representative cases.

(A, B) Monozygote (MZ) twins with axial length (AL) > 24 mm. (C, D) MZ twins with AL < 24 mm. The areas and the locations of PPA are similar between MZ twins. Though the PPA area was shown to be correlated with AL, there were some exceptions that are thought to be associated with familial inheritance. MZ twin eyes with shorter AL (D) show greater PPA areas compared to the other MZ twin eyes with longer AL (A). The angular locations of retinal veins show various values even between MZ twins.