Oculocutaneous Albinism Carrier Identifiable With OCT, Regardless of Disease Activity

Carriers of the gene associated with oculocutaneous albinism (OCA), whether they have active disease or not, portray subtle, but consistent foveal abnormalities, according to a study published in the British Journal of Ophthalmology. The finding raises the possibility that mild or isolated foveal hypoplasia could act as a biomarker for OCA carrier status, investigators suggest. 

The cross-sectional study examined the parents of 16 patients with OCA who were recruited at Leicester Royal Infirmary in the UK (n=28, mean age 40.43±8.07), as well as 28 age- and refraction-matched volunteers as a control group. Participants underwent spectral domain ocular coherence tomography (SD-OCT), as well as qualitative and quantitative foveal analysis from April 2017 to December 2019.

“Examining and subsequently identifying subtle carrier signs in parents increases the index of suspicion for the child to have albinism and adds to the diagnostic accuracy,” the investigation explains. Of the gene carriers, 32.14% displayed grade 1a or 1b foveal hypoplasia. Mothers and fathers in the case group showed significantly greater total retinal layer (TRL) thickness (P =.009) and inner retinal layer (IRL) thickness in the central fovea region (P <.001) compared with control individuals. No difference was found between carriers and noncarriers for outer retinal layer (ORL) thickness (P =.432).

In contrast, best-corrected visual acuity (BCVA) did not meaningfully differ between case parents and those in the control group (P =.83). However, 2 parents with grade 1b hypoplasia had less sharp BCVA than those with grade 1a or no hypoplasia. Researchers speculate that genetic carriers successfully develop cone photoreceptor specialization, thus enabling satisfactory acuity. Also, since hypoplasia in carriers was limited to grade 1, genetic variants may have affected their retinal development later in the process of specialization.

In the temporal parafoveal region, the case set exhibited a thinner TRL compared with control participants, due to IRL thinning in this area — specifically, thinning of the temporal ganglion cell-inner plexiform layer complex (P <.001). Carriers also showed significant thinning at the perifoveal nasal TRL, a product of nasal IRL thinning (P =.02). No important differences were found between cohorts for ORL thickness in parafoveal and perifoveal regions.

Variants found in parent genotyping included OCA2, SLC45A2, tyrosinase gene (TYR), along with heterozygous TYR haplotype. Sequence analysis was conducted for 75% of case offspring, and genotyping performed for 57.1% of their parents. The partial genetic data represents a study limitation.

Prior findings reveal persistence of the IRL in carriers of ocular albinism, thus the current work on OCA contributes to clinical knowledge, especially in cases when phenotype information is incomplete. In new patients, mild structural irregularities are perplexing, and “it is possible that some cases with mild (grade 1) ‘idiopathic foveal hypoplasia’ could be a manifestation of carrier status for albinism,” the investigation added.

The study was limited in that researchers had incomplete genetic data, which prevented them from being able to fully characterize the genotype-phenotype relationships of the carriers. Also, the number of participants was small, although the sample size calculation power was sufficient. 

Reference

Kuht HJ, Thomas MG, McLean RJ, et al. Abnormal foveal morphology in carriers of oculocutaneous albinism. Br J Ophthalmol. Published online April 4, 2022. doi:10.1136/bjophthalmol-2020-318192