Discussion

Zika virus is a single-stranded RNA arbovirus of the Flaviviridae family that is generally transmitted by the Aedes aegypti mosquito. In adults, ZKV infection is typically asymptomatic, but when symptoms occur, patients report flu-like symptoms such as fever, headache, conjunctivitis, rash, and joint pain lasting days to weeks.^{1 - 5} Vertical transmission to a fetus is reported and confirmed to occur when a mother is exposed to ZKV during the pregnancy. Children infected in utero, especially within the first or second trimester, tend to have a much more serious presentation. In early intrauterine infections, more first- and early second-trimester developmental processes, like neuronal migration, neuronal differentiation, sulcation/gyration, and myelination processes, may be impacted, eventually resulting in more severe brain malformations. Manifestations of congenital infection include severe microcephaly, joint contractures, hearing impairments, hypertonia, and ocular findings like chorioretinal atrophy, retinal pigment epithelium mottling, optic nerve hypoplasia or atrophy, iris coloboma, microphthalmia, and lens subluxation.^{1 - 6} This constellation of abnormal central nervous system (CNS) and optic findings is known as congenital Zika syndrome (CZS).

The difference in presentation between adults and children is likely due to the ZKV’s tropism for undifferentiated neurons over differentiated neurons.^{1 - 3} Intrauterine infection, especially in early pregnancy, can have devastating effects on the fetus, resulting in an overall decrease in neurons and consequently a number of brain abnormalities.^{1, 3} Studies have also revealed that cells lining the blood–retinal barrier, retinal endothelium, and retinal pigment epithelium have an increased susceptibility to ZKV-induced cell death.^{1, 3} As a result, extensive research has been conducted to investigate ocular manifestations (in addition to the CNS findings) in individuals with ZKV infection. These studies have demonstrated that ocular abnormalities, especially macular atrophy, occur so frequently in CZS that they may serve as valuable diagnostic indicators for ZKV infection, even in the absence of microcephaly.^{1 - 3} Recent efforts have also given clinicians ways to differentiate ZKV from other similarly presenting pathologies like rubella and toxoplasmosis.¹ Chorioretinal colobomas however are a much more rare presentation with only a few cases reported in the current literature.^{1, 3, 5, 6} To understand how chorioretinal colobomas occur in CZS, it is essential to discuss what colobomas are, as well as how and when they form.

Colobomas are focal discontinuities or areas of missing tissue in the eye’s structure.⁷ They occur when the embryonic choroidal fissure fails to completely close during weeks 5-7 of fetal life.^{7, 8} They can present anteriorly in the iris or ciliary body, or more rarely, posteriorly in the choroid, retina, or optic nerve.⁷ Those diagnosed with posterior colobomas tend to be older in age.^{7, 8} Patients with chorioretinal colobomas have a significantly increased risk for retinal detachment, with an incidence reported as high as 42%.⁸ Given the emergency of this complication, prompt diagnosis and patient education of red-flag symptoms are key. This is especially important in patients with diseases such as CHARGE (Coloboma, Heart defects, Atresia choanae, Retardation of growth, Genital abnormalities, and Ear abnormalities) syndrome, VATER (Vertebrae, Anus, Trachea, Esophagus, and Renal) syndrome, MPPC (Microcornea, Posterior megalolenticonus, Persistent fetal vasculature, and Chorioretinal coloboma) syndrome, and DiGeorge syndrome where chorioretinal colobomas can occur.^{7, 8}

ZKV’s neurotropism for undifferentiated neurons, in conjunction with our knowledge of posterior coloboma formation and presentation, allows us to form a reasonable hypothesis for why chorioretinal colobomas are so rare in ZKV patients. First, to develop a coloboma, fetal exposure to ZKV must occur early in the first trimester as colobomas typically form within weeks 5-7.⁷ Second, to find a chorioretinal or optic nerve coloboma, a patient must undergo a thorough ophthalmologic evaluation, likely with neuroimaging included. Given this knowledge, it is crucial for newborns suspected of early intrauterine ZKV infection to be promptly screened for orbit abnormalities via comprehensive ophthalmologic and neuroimaging evaluations. In cases of severe microcephaly, radiologists specifically should place special emphasis on studying the eyes in addition to the brain to prevent these ophthalmologic findings from being missed.