Study: Ganglion Cell, Inner Plexiform Layer Thickness Influenced by Genetics

Light micrograph of multiple layers of different cells in eyeball tissue,40x,hematoxylin and eosin staining
Researchers investigated heritability factors that may influence changes to macular ganglion cell inner plexiform layer thickness.

According to researchers, genetic factors significantly influence macular ganglion cell inner plexiform layer (GCIPL) thickness. Heritability ranges from moderate to high in all subfields, which are defined by the Early Treatment Diabetic Retinopathy Study (ETDRS). These findings may be relevant in the early detection of glaucoma, according to the investigators

By using optical coherence tomography (OCT) images, the authors of the study published in The British Journal of Ophthalmology could analyze the thickness of GCIPL. 

“Many studies using OCT revealed changes in GCIPL thickness in various diseases and conditions, such as age-related macular degeneration, diabetic macular edema, glaucoma, and after epiretinal membrane peeling and panretinal photocoagulation,” according to the researchers. 

It’s also noted that the change in GCIPL thickness could “provide discrimination between normal eyes and eyes with early glaucoma.” Patients with early glaucoma could present with a GCIPL thickness change before any visual field defects are detected, the report shows. 

To investigate how significantly genetic factors influence macular GCIPL, researchers evaluated 361 participants who were part of the Healthy Twin Study in Korea. The study is a “nationwide, prospective cohort study that recruited adult Korean twins and their family members to investigate genetic and environmental determinants of a wide range of traits.” All participants (133 men, 228 women, 102 monozygotic twins, 8 dizygotic twins, 122 parents and siblings from 89 families) underwent macular volumetric OCT scans as part of the Healthy Twin Study from May through December 2012.

A self-administered questionnaire was also used to gather information about participants’ current treatments for hypertension, diabetes mellitus and smoking habits. 

To estimate the heritability of macular GCIPL thickness, researchers “fitted a variance decomposition model and partitioned the total phenotypic variation of macular GCIPL thickness measures into additive genetic (бa2), shared environmental component within a family (бc2) and individual-specific unique environmental components (бe2).”

They write, “The key assumption of this model is that the effects of shared environmental factors are common to the members of a family and that the three factors (бa2, бc2 and бe2) have independent and additive effects on the trait variance.”

Essentially, intraclass correlation coefficients (ICC) of GCIPL thickness by various configurations of family relationships were estimated to evaluate intrafamilial resemblance. That data was then used to estimate heritability of GCIPL thickness.

The researchers found that “monozygotic twin pairs showed significantly higherICC of GCIPL thickness in all subfields compared to those in parent-offspring pairs and sibling pairs. GCIPL thickness showed moderate to high heritability in all subfields, and the heritability of average GCIPL thickness was 0.82. Heritability of GCIPL thickness in outer subfields was 0.69, 0.67, 0.72 and 0.68 for superior, inferior, temporal and nasal fields, respectively. Heritability of GCIPL thickness in inner subfields was 0.55, 0.56, 0.75 and 0.50 for superior, inferior, temporal and nasal subfields, respectively.”

Since this study reveals strong genetic influence on GCIPL thickness, it’s suggested that practitioners consider these findings to detect early glaucoma in patients. 


Kong M, Hwang S, Ko H, et al. Heritability of macular ganglion cell inner plexiform layer thickness as determined by optical coherence tomography: the Healthy Twin Study. Br J Ophthalmol. Updated August 26, 2020. Accessed September 30, 2020. doi:10.1136/bjophthalmol-2020-316512