Fig 2 - uploaded by João Rafael de Oliveira Dias
Content may be subject to copyright.
A. A fundus image shows gross pigment mottling and hypopigmented areas in the paramacular location of the left eye. B. Swept source OCT of the retina reveals normal retina layers and choroid without abnormalities (horizontan B-scan, blue and green arrows).
Source publication
Background/purpose:
To describe the ocular findings of two infants with congenital Zika syndrome born in São Paulo state, Brazil, outside the primary outbreak region.
Methods:
Two female infants with congenital Zika syndrome were submitted to a complete screening for infectious diseases, as well as ocular examination, fundus photography, and opt...
Contexts in source publication
Context 1
... child had normal anterior segment structures. The infant presented clustered bone-spicule pigmentary clumping in the paramacular location of both eyes, surrounded by hypopigmented areas (Figure 2A). Periph- ery was normal in both eyes. ...
Citations
... Four articles shown in Table 5 investigated OCT results in congenital ZIKV cases. 28,31,37,38 Severe damage of the neurosensory retina and choroid were reported. OCT in 13 neonates with congenital Zika virus infection showed tomographic abnormalities in almost all cases. ...
... Immunohistochemical studies demonstrated Zika virus antigen expression in the retina, choroid, and optic nerve. 28,31,37,38 Clinical features, OCT analysis, and histopathological studies highlight both the neurotropism of ZKV and the devastating effect of this virus on retinal tissue and the optic nerve. ...
Objective:
To assess fetal and neonatal eyes abnormalities and their progression during the last ZIKV outbreak and summarize learned lessons.
Methods:
A systematic review and meta-analysis was conducted by a team of obstetricians and ophthalmologists.
Results:
Studies reporting ocular abnormalities during the prenatal (n = 5) and postnatal (n = 24) periods were included in the analysis. In the prenatal period, the most common ocular findings were intraocular calcification cases (4/6, 66.6%) and microphthalmia (3/6, 50%). Postnatal ocular abnormalities of congenital ZIKV infection were described after birth in 479 cases. Among them microphthalmia was reported in 13 cases (13/479, 2.7%). Posterior segment (retina and optic nerve) was the most affected structure, consisting of pigmentary changes (229/479, 47.8%), macular chorioretinal atrophy (216/479, 45%), optic nerve atrophy (181/479, 37.8%), increased cup-to-disk ratio (190/479, 39.6.%), optic nerve hypoplasia (93/479,19.4%), vascular changes (26/479, 5.4%), and retinal coloboma (20/479, 4.1%). The anterior segment was involved in 4.6% (22/479) of cases, including cataract (9/479, 1.8%), lens subluxation (1/479, 0.2%), iris coloboma (5/479, 1%), and congenital glaucoma (7/479, 1.4%). These ocular anomalies were isolated in one case (1/479, 0.2%) and multiple anomalies were found in the other cases. Long-term visual disorders have been described, with no possible improvement and even a worsening of some of the ocular anomalies previously observed. No reactivation of ocular lesions was observed.
Conclusion:
This review highlights the severe ocular abnormalities associated with congenital ZIKV infections. The importance of multidisciplinary communication between the obstetrician, the maternal-fetal medicine specialist, and the ophthalmologist is emphasized.
Protocol registration:
This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration440 188.
... [133][134][135][136] Other changes included pigmentary clumping, coloboma, subretinal hemorrhages, vascular tortuosity, and abnormal retinal vessels with focal vascular dilation. [137][138][139][140] Iris colobomas, microcornea, microphthalmia, lens subluxation, cataracts, intraocular calcification, congenital glaucoma, strabismus, and nystagmus were also seen in some infants. [141][142][143][144][145] The eye findings in CZS were not progressive. ...
... Additional studies in different regions in Brazil confirmed these findings later on in 2017 by de Oliveira and Zin [86,92]. However, Zin et al. reported the presence of retinal hemorrhage, which was not previously mentioned. ...
Zika virus (ZIKV) is mosquito-borne flavivirus that caused a significant public health concern in French Polynesia and South America. The two major complications that gained the most media attention during the ZIKV outbreak were Guillain–Barré syndrome (GBS) and microcephaly in newborn infants. The two modes of ZIKV transmission are the vector-borne and non-vector borne modes of transmission. Aedes aegypti and Aedes albopictus are the most important vectors of ZIKV. ZIKV binds to surface receptors on permissive cells that support infection and replication, such as neural progenitor cells, dendritic cells, dermal fibroblasts, retinal pigment epithelial cells, endothelial cells, macrophages, epidermal keratinocytes, and trophoblasts to cause infection. The innate immune response to ZIKV infection is mediated by interferons and natural killer cells, whereas the adaptive immune response is mediated by CD8+T cells, Th1 cells, and neutralizing antibodies. The non-structural proteins of ZIKV, such as non-structural protein 5, are involved in the evasion of the host’s immune defense mechanisms. Ocular manifestations of ZIKV arise from the virus’ ability to cross both the blood–brain barrier and blood-retinal barrier, as well as the blood-aqueous barrier. Most notably, this results in the development of GBS, a rare neurological complication in acute ZIKV infection. This can yield ocular symptoms and signs. Additionally, infants to whom ZIKV is transmitted congenitally develop congenital Zika syndrome (CZS). The ocular manifestations are widely variable, and include nonpurulent conjunctivitis, anterior uveitis, keratitis, trabeculitis, congenital glaucoma, microphthalmia, hypoplastic optic disc, and optic nerve pallor. There are currently no FDA approved therapeutic agents for treating ZIKV infections and, as such, a meticulous ocular examination is an important aspect of the diagnosis. This review utilized several published articles regarding the ocular findings of ZIKV, antiviral immune responses to ZIKV infection, and the pathogenesis of ocular manifestations in individuals with ZIKV infection. This review summarizes the current knowledge on the viral immunology of ZIKV, interactions between ZIKV and the host’s immune defense mechanism, pathological mechanisms, as well as anterior and posterior segment findings associated with ZIKV infection.
... RNA virus epidemics continue to threaten human health, with epidemics caused by Zika virus (ZIKV), Ebola virus (EBOV), Dengue virus (DENV), Chikungunya virus (CHIKV), and more recently the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic [1][2][3][4]. We previously reported ocular complications due to flaviviruses [5], especially those caused by ZIKV [6][7][8]. ...
Several RNA viruses, including SARS-CoV-2, can infect or use the eye as an entry portal to cause ocular or systemic diseases. Povidone-Iodine (PVP-I) is routinely used during ocular surgeries and eye banking as a cost-effective disinfectant due to its broad-spectrum antimicrobial activity, including against viruses. However, whether PVP-I can exert antiviral activities in virus-infected cells remains elusive. In this study, using Zika (ZIKV) and Chikungunya (CHIKV) virus infection of human corneal and retinal pigment epithelial cells, we report antiviral mechanisms of PVP-I. Our data showed that PVP-I, even at the lowest concentration (0.01%), drastically reduced viral replication in corneal and retinal cells without causing cellular toxicity. Antiviral effects of PVP-I against ZIKV and CHIKV were mediated by direct viral inactivation, thus attenuating the ability of the virus to infect host cells. Moreover, one-minute PVP-I exposure of infected ocular cells drastically reduced viral replication and the production of infectious progeny virions. Furthermore, viral-induced (CHIKV) expression of inflammatory genes (TNF-α, IL-6, IL-8, and IL1β) were markedly reduced in PVP-I treated corneal epithelial cells. Together, our results demonstrate potent antiviral effects of PVP-I against ZIKV and CHIKV infection of ocular cells. Thus, a low dose of PVP-I can be used during tissue harvesting for corneal transplants to prevent potential transmission of RNA viruses via infected cells.
... Because NHPs are evolutionarily close to humans, it is not surprising that these animals and their reproductive tract are anatomically and physiologically more similar to humans than other models such as mice; thus, NHPs are often considered to be one of the most relevant animal models [85,86]. Unlike mice, immunocompetent NHPs are more suitable to study ZIKV infections, although the extent to which disease is mimicked is difficult to assess and varies with NHP species. ...
... The main OCT findings in the affected eyes included disruption of the ellipsoid zone and hyperreflectivity underlying the retinal pigment epithelium, thinning of the retina and choroid, and a colobomatous excavation [84]. Oliveira et al. described that the OCT results show a wide range of retinal damage caused by congenital ZIKV infection, and reinforced the findings compatible with chorioretinal atrophy [85]. Campos et al. described a case report with similar findings that correspond to retina thinning with atrophy of the external retina, including the outer nuclear layer and the ellipsoid zone, associated with hyperreflectivity of the RPE and increased OCT penetration into deeper layers of the choroid and sclera (Figure 4) [86]. ...
Zika is an arboviral disease that has caused a significant impact, especially in the Americas after the epidemics in 2015 and 2016. The World Health Organization (WHO) declared it as a Public Health Emergency of International Concern (PHEIC) in 2016, linking it with the Guillain-Barré syndrome and especially the microcephaly and the Congenital Zika Syndrome. The multiple consequences, especially in the central and peripheral nervous system in the short and long term, are still to be better defined. Therefore research on Zika is crucial. This book presents an update of the significant epidemiological and clinical research of Zika over the last years in many aspects and from a multinational perspective.
... The main OCT findings in the affected eyes included disruption of the ellipsoid zone and hyperreflectivity underlying the retinal pigment epithelium, thinning of the retina and choroid, and a colobomatous excavation [84]. Oliveira et al. described that the OCT results show a wide range of retinal damage caused by congenital ZIKV infection, and reinforced the findings compatible with chorioretinal atrophy [85]. Campos et al. described a case report with similar findings that correspond to retina thinning with atrophy of the external retina, including the outer nuclear layer and the ellipsoid zone, associated with hyperreflectivity of the RPE and increased OCT penetration into deeper layers of the choroid and sclera (Figure 4) [86] . ...
Ocular involvement in Zika virus (ZIKV) infection can be present both in adults and infants as acquired and congenital diseases respectively. Through experimental studies, there has been clarified important mechanisms of ocular pathogenesis that allow the establishment of potential objectives for antiviral drugs development. The spread of the virus at the ocular level could be hematogenous or axonal, however the hematogenous route through the choroid is suggested as the most important initial mechanism for infection. Ocular manifestations vary according to the age of presentation, being mild and self-limited in adults and potentially devastating in children, related to congenital Zika syndrome (CZS). Ocular diagnosis is made based in clinical features and contact/travel history to countries of epidemiological importance; fundoscopy, optical coherence tomography, fluoresceinic/green indocianine angiography, cultures, serological and molecular tests are useful diagnostic tools. Ocular management is focused according to the clinical context of each patient. Prevention is carried out in a comprehensive manner and further research is directed to vaccine development and specific antiviral treatment. Proper attention requires a multidisciplinary team in order to reach complete visual evaluation and early rehabilitation.
... A number of clinical studies have reported ocular anomalies, specifically in the retina and choroid, of infants with congenital ZIKV infection. [195][196][197][198][199] ZIKV invasion of ophthalmic tissues resulted in adverse illnesses, which include optic neutitis, chorioretinal atrophy, circumscribed pigment, iris colobomas, and lens subluxation, and blindness in neonates, and conjunctivitis and uveitis in adults, 56,200 have been reported. In addition, AXL expression has been observed in the outer margin of the neural retina and in cells of the ciliary marginal zone adjacent to neural retina, 180,201 suggesting a possible underlying mechanism for macular atrophy (leading to blindness) in babies born to ZIKV-infected mothers. ...
Although the World Health Organization declared an end to the recent Zika virus (ZIKV) outbreak and its association with adverse fetal and pediatric outcome, on November 18, 2016, the virus still remains a severe public health threat. Laboratory experiments thus far supported the suspicions that ZIKV is a teratogenic agent. Evidence indicated that ZIKV infection cripples the host cells’ innate immune responses, allowing productive replication and potential dissemination of the virus. In addition, studies suggest potential transplacental passage of the virus and subsequent selective targeting of neural progenitor cells (NPCs). Depletion of NPCs by ZIKV is associated with restricted brain growth. And while microcephaly can result from infection at any gestational stages, the risk is greater during the first trimester. Although a number of recent studies revealed some of specific molecular and cellular roles of ZIKV proteins of this mosquito-borne flavivirus, the mechanisms by which it produces it suspected pathophysiological effects are not completely understood. Thus, this review highlights the cellular and molecular evidence that implicate ZIKV in fetal and pediatric neuropathologies.
... The constellation of abnormalities associated with the virus is described as congenital Zika syndrome (CZS). Reports in the literature have described vision-limiting retina and optic nerve abnormalities such as atrophic retina, pigmentary changes, and optic nerve pallor in infants [4][5][6][7][8]. ...
... Multiple studies from Brazil, Colombia, and Venezuela have described ophthalmic findings associated with CZS. The most commonly reported findings affect the posterior segment and include circumscribed macular chorioretinal atrophy, RPE mottling, and optic nerve abnormalities including hypoplasia, increased cup:disk ratio, atrophy, and pallor [6][7][8]22]. The majority of findings are bilateral [7]. ...
Background:
As the number of children with Zika virus-related complications grows, the long-term developmental trajectory and its effects on families are unknown. We present the first known case of congenital Zika syndrome seen at our institution with significant fundus findings.
Case presentation:
A 3-day-old Hispanic baby girl presented with severe microcephaly of 24 cm and temperature instability at birth. Her mother had traveled to Honduras early in pregnancy and testing of amniotic fluid was positive for Zika virus via polymerase chain reaction. A dilated fundus examination was significant for bilateral severe colobomatous chorioretinal atrophy of the macula and pigmentary changes. Neonatal magnetic resonance imaging revealed diffuse lissencephaly with decreased brain volume, atrophic corpus callosum and brainstem, periventricular calcifications, and ventriculomegaly of the lateral ventricles.
Conclusions:
Our patient, who presented with the first known case of congenital Zika syndrome in Northern Florida, demonstrated profound bilateral colobomatous chorioretinal atrophy of the macula. The ophthalmologic findings along with severe microcephaly emphasize the neurotropism of the Zika virus, and ultimately are indicative of poor developmental and visual prognosis for affected infants. With the increased prevalence of Zika virus, ophthalmologists should be aware of the associated findings and the importance of an eye-screening examination with a dilated fundus examination within 1 month of life of infants in which congenital Zika syndrome is suspected. A multidisciplinary care approach is essential for the care of affected infants and their families.
... OCT findings in children with CZS were described in children from Recife (Ventura et al., 2016f;Campos et al., 2016) and São Paulo (de Oliveira Dias et al., 2017) cities, Brazil. A study in Recife described for the first time the OCT findings in infants with positive retinal findings and CZS (Ventura et al., 2016f). ...
... The OCT images revealed a discontinuation of the ellipsoid zone and hyperreflectivity underlying the retinal pigment epithelium, retinal thinning, choroidal thinning, and a colobomatouslike appearance. In addition, in subsequent reports, de Oliveira Dias et al 23 and Campos et al 24 described similar OCT findings in infants with CZS that corroborated the initial OCT study. The importance of these 2 studies is that they indicated how severely ZIKV affects the fetal eye, causing severe and irreversible retinal and choroidal damage. ...
Vision plays an important role in the development of communication, social interaction, spatial awareness, and the motor skills needed to explore the environment. In the past 2 years, researchers have described the broad spectrum of clinical features that comprise congenital Zika syndrome (CZS). The ocular manifestations are considered 1 important pillar of this new entity. The most characteristic ophthalmic findings include chorioretinal scars and focal pigmentary changes seen in the macular region. Since these findings were first reported, other researchers have validated and extended them, leading to a more complete picture of the spectrum of ocular manifestations related to CZS. In this article, we summarize the current knowledge on the ocular implications of CZS and emphasize the importance of early rehabilitation to enhance visual performance in affected children.
