Table Info

Table 3.

Ophthalmic manifestations in CZS

Study	Demographics	Findings
Costa and Freitas 2022 [22] Cross-sectional case series study	• Cohort of 56 infants with CZS and microcephaly • Mean age 5.25 months ± 3.65 months • Females (n = 27), males (n = 29)	• Affected retina (79.2%, n = 19) and affected optic nerve (66.7%, n = 16) • Gross retinal pigmentation (45.8%, n = 11) • Macular chorioretinal atrophy/scarring (45.8%, n = 11) • Optic nerve hypoplasia (4.2%, n = 1) • Optic nerve increased cup-to-disk ratio (8.3%, n = 2) • Optic nerve pallor (58.3%, n = 14)
Ventura et al. 2017 [23] Cross-sectional case series study	• Cohort of 32 infants with CZS • Age range 4 months to 7 months • Females (n = 15), males (n = 18)	• Microcephaly (n = 29) • Exotropia (34.4%, n = 11) • Esotropia (31.3%, n = 10) • Strabismus (9.4%, n = 3) • Nystagmus (28.1%, n = 9) • Astigmatism (45.3%, 29 of 64 eyes), Hyperopia (40.6%, 26 of 64 eyes), myopia (7.8%, 5 of 64 eyes) • Optic nerve hypoplasia (7.8%, 5 of 64 eyes) • Pallor (7.8%, 5 of 64 eyes) • Chorioretinal scar (17.2%, 11 of 64 eyes) • Pigment mottling (28.1%, n = 9) • Bilateral hypopigmented lesion (3.1%, n = 1) • Retinal vessel attenuation (3.1%, 2 eyes)
de Paula Freitas et al. 2017 [24] Cross-sectional case series study	• Cohort of 29 infants with CZS • Age range 1 month to 6 months • Females (n = 18), males (n = 11)	• Microcephaly (34.5%, n = 10) • Ocular abnormalities (n = 10) • Ophthalmoscopic abnormalities (17 of 20 eyes in 10 children) • Ocular lesions (70%, n = 7) • Chorioretinal atrophy (64.7%, 11 of 17 eyes) • Severe chorioretinal atrophy in the macula (3 of 17 eyes), nasal retina (3 of 17 eyes), paramacular area (5 of 17 eyes) • Optic nerve abnormalities (47.1%, 8 of 17 eyes) • Bilateral iris coloboma (11.8%, 2 eyes of the same patient) • Lens subluxation (5.9%, 1 of 17 eyes)
Ventura et al. 2016 [25] Case series	• 3 neonates born at 37 weeks to 38 weeks gestation with microcephaly and cerebral calcifications, presumed intrauterine Zika infection • Females (n = 2), males (n = 1)	• Gross macular pigment mottling (n = 3) • Foveal reflex loss (n = 3) • Macular neuroretinal atrophy (n = 1) • Fundoscopic alterations in the macular region (n = 3)

Study

Demographics

Findings

Costa and Freitas 2022 [22]

Cross-sectional case series study

• Cohort of 56 infants with CZS and microcephaly

• Mean age 5.25 months ± 3.65 months

• Females (n = 27), males (n = 29)

• Affected retina (79.2%, n = 19) and affected optic nerve (66.7%, n = 16)

• Gross retinal pigmentation (45.8%, n = 11)

• Macular chorioretinal atrophy/scarring (45.8%, n = 11)

• Optic nerve hypoplasia (4.2%, n = 1)

• Optic nerve increased cup-to-disk ratio (8.3%, n = 2)

• Optic nerve pallor (58.3%, n = 14)

Ventura et al. 2017 [23]

Cross-sectional case series study

• Cohort of 32 infants with CZS

• Age range 4 months to 7 months

• Females (n = 15), males (n = 18)

• Microcephaly (n = 29)

• Exotropia (34.4%, n = 11)

• Esotropia (31.3%, n = 10)

• Strabismus (9.4%, n = 3)

• Nystagmus (28.1%, n = 9)

• Astigmatism (45.3%, 29 of 64 eyes), Hyperopia (40.6%, 26 of 64 eyes), myopia (7.8%, 5 of 64 eyes)

• Optic nerve hypoplasia (7.8%, 5 of 64 eyes)

• Pallor (7.8%, 5 of 64 eyes)

• Chorioretinal scar (17.2%, 11 of 64 eyes)

• Pigment mottling (28.1%, n = 9)

• Bilateral hypopigmented lesion (3.1%, n = 1)

• Retinal vessel attenuation (3.1%, 2 eyes)

de Paula Freitas et al. 2017 [24]

Cross-sectional case series study

• Cohort of 29 infants with CZS

• Age range 1 month to 6 months

• Females (n = 18), males (n = 11)

• Microcephaly (34.5%, n = 10)

• Ocular abnormalities (n = 10)

• Ophthalmoscopic abnormalities (17 of 20 eyes in 10 children)

• Ocular lesions (70%, n = 7)

• Chorioretinal atrophy (64.7%, 11 of 17 eyes)

• Severe chorioretinal atrophy in the macula (3 of 17 eyes), nasal retina (3 of 17 eyes), paramacular area (5 of 17 eyes)

• Optic nerve abnormalities (47.1%, 8 of 17 eyes)

• Bilateral iris coloboma (11.8%, 2 eyes of the same patient)

• Lens subluxation (5.9%, 1 of 17 eyes)

Ventura et al. 2016 [25]

Case series

• 3 neonates born at 37 weeks to 38 weeks gestation with microcephaly and cerebral calcifications, presumed intrauterine Zika infection

• Females (n = 2), males (n = 1)

• Gross macular pigment mottling (n = 3)

• Foveal reflex loss (n = 3)

• Macular neuroretinal atrophy (n = 1)

• Fundoscopic alterations in the macular region (n = 3)

Declarations

Acknowledgments

We are grateful for the support of Dr. Branka Filipovic, head of research, at the Saint James School of Medicine, for her early input in designing this study. We thank Mr. Oscar Andrade, chief librarian, at the Saint James School of Medicine, as well as the Kean University Library Nancy Thompson Learning Commons for assistance with accessing the full-text, peer-reviewed articles that were needed to conduct this review.

Author contributions

Dhaara S and Dhairavi S: Conceptualization, Methodology, Investigation, Writing—original draft, Writing—review & editing. OM: Conceptualization, Methodology, Investigation, Writing—original draft. RZ: Conceptualization, Methodology, Investigation, Writing—review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

The data and materials obtained for this systematic review were obtained online using search engines and the research databases mentioned in the methodology. The articles referenced in this paper can be accessed freely by searching for them on PubMed, PMC, Ovid, Cochrane, or Google Scholar.

Funding

This research was supported by Kean University Office of Research and Sponsored Programs (ORSP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Zika virus [Internet]. Geneva: World Health Organization; c2024 [cited 2023 Dec 31]. Available from: https://www.who.int/news-room/fact-sheets/detail/Zika-virus

Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects — reviewing the evidence for causality. N Engl J Med. 2016;374:1981–7. [DOI] [PubMed]

Microcephaly & other birth defects [Internet]. U.S. Department of Health and Human Services; [cited 2023 Jul 18]. Available from: https://www.cdc.gov/Zika/healtheffects/birth_defects.html

Moore CA, Staples JE, Dobyns WB, Pessoa A, Ventura CV, Fonseca EB, et al. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr. 2017;171:288–95. [DOI] [PubMed] [PMC]

McAllister JC, Porcelli M, Medina JM, Delorey MJ, Connelly CR, Godsey MS, et al. Mosquito control activities during local transmission of Zika virus, Miami-Dade County, Florida, USA, 2016. Emerg Infect Dis. 2020;26:881–90. [DOI] [PubMed] [PMC]

Salmeron ACA, Bezerra WP, de Souza RLL, Pereira LC, do Nascimento LM, Branco ACCC, et al. Immunological imbalance in microcephalic children with congenital Zika virus syndrome. Med Microbiol Immunol. 2022;211:219–35. [DOI] [PubMed]

Rua EC, de Oliveira SA, de Oliveira Vianna RA, Dalcastel LAB, de Castro Sarmet Dos Santos TC, Cardoso CAA, et al. Two-year follow-up of children with congenital Zika syndrome: the evolution of clinical patterns. Eur J Pediatr. 2022;181:991–9. [DOI] [PubMed]

Nunes ML, Esper NB, Franco AR, Radaelli G, Soder RB, Bomfim R, et al. Epilepsy after congenital Zika virus infection: EEG and neuroimaging features. Seizure. 2021;84:14–22. [DOI] [PubMed]

Nascimento-Carvalho GC, Nascimento-Carvalho EC, Ramos CL, Vilas-Boas AL, Moreno-Carvalho OA, Vinhaes CL, et al. Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid. Sci Rep. 2021;11:8474. [DOI] [PubMed] [PMC]

10.

Cavalcante TB, Ribeiro MRC, Sousa PDS, Costa EPF, Alves MTSSBE, Simões VMF, et al. Congenital Zika syndrome: growth, clinical, and motor development outcomes up to 36 months of age and differences according to microcephaly at birth. Int J Infect Dis. 2021;105:399–408. [DOI] [PubMed]

11.

Štrafela P, Vizjak A, Mraz J, Mlakar J, Pižem J, Tul N, et al. Zika virus–associated micrencephaly: a thorough description of neuropathologic findings in the fetal central nervous system. Arch Pathol Lab Med. 2017;141:73–81. [DOI] [PubMed]

12.

Driggers RW, Ho CY, Korhonen EM, Kuivanen S, Jääskeläinen AJ, Smura T, et al. Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med. 2016;374:2142–51. [DOI] [PubMed]

13.

Mlakar J, Korva M, Tul N, Popović M, Poljšak-Prijatelj M, Mraz J, et al. Zika virus associated with microcephaly. N Engl J Med. 2016;374:951–8. [DOI] [PubMed]

14.

Cavalheiro S, Lopez A, Serra S, Da Cunha A, da Costa MDS, Moron A, et al. Microcephaly and Zika virus: neonatal neuroradiological aspects. Childs Nerv Syst. 2016;32:1057–60. [DOI] [PubMed] [PMC]

15.

Sarno M, Sacramento GA, Khouri R, do Rosário MS, Costa F, Archanjo G, et al. Zika virus infection and stillbirths: a case of hydrops fetalis, hydranencephaly and fetal demise. PLoS Negl Trop Dis. 2016;10:e0004517. [DOI] [PubMed] [PMC]

16.

Magalhães AF, Caldas C, de Lucca VI. Hip dysplasia in congenital Zika syndrome: a 5 year follow-up. Int J Pediatr Res. 2023;9:103. [DOI]

17.

da Fonseca JO, de Oliveira Vianna RA, Carvalho FR, Velarde LGC, de Oliveira SA, Cardoso CAA, et al. The hip of children with congenital Zika syndrome: a prospective observational study. J Pediatr. 2023;256:27–32. [DOI] [PubMed]

18.

Matos MA, Nascimento MAST, Merriman JW. Orthopaedic approach to the congenital Zika syndrome. Int Orthop. 2021;45:559–64. [DOI] [PubMed]

19.

Contreras-Capetillo SN, Palma-Baquedano JR, Valadéz-González N, Manrique-Saide P, Barrera-Pérez HA, Pinto-Escalante D, et al. Case report: congenital arthrogryposis and unilateral absences of distal arm in congenital Zika syndrome. Front Med (Laussane). 2021;8:499016. [DOI] [PubMed] [PMC]

20.

Tavares JS, Gama GL, Dias Borges MC, de Sousa Santos AC, Tavares JS, Amorim MMR, et al. Classification of congenital Zika syndrome: muscle tone, motor type, body segments affected, and gross motor function. Dev Neurorehabil. 2021;24:296–302. [DOI] [PubMed]

21.

van der Linden H, Silveira-Moriyama L, van der Linden V, Pessoa A, Valente K, Mink J, et al. Movement disorders in children with congenital Zika virus syndrome. Brain Dev. 2020;42:720–9. [DOI] [PubMed]

22.

Costa CBDC, Freitas D. Ocular findings of congenital Zika virus infection with microcephaly. Int Ophthalmol. 2022;42:3117–27. [DOI] [PubMed]

23.

Ventura LO, Ventura CV, Lawrence L, van der Linden V, van der Linden A, Gois AL, et al. Visual impairment in children with congenital Zika syndrome. J AAPOS. 2017;21:295–9.e2. [DOI] [PubMed]

24.

de Paula Freitas B, de Oliveira Dias JR, Prazeres J, Sacramento GA, Ko AI, Maia M, et al. Ocular findings in infants with microcephaly associated with presumed Zika virus congenital infection in Salvador, Brazil. JAMA Ophthalmol. 2016;134:529–35. [DOI] [PubMed] [PMC]

25.

Ventura CV, Maia M, Bravo-Filho V, Góis AL, Belfort R Jr. Zika virus in Brazil and macular atrophy in a child with microcephaly. Lancet. 2016;387:228. [DOI] [PubMed]

26.

Muniz LF, Maciel RJF, Ramos DS, Albuquerque KMG, Leão ÂC, Van Der Linden V, et al. Audiological follow-up of children with congenital Zika syndrome. Heliyon. 2022;8:e08720. [DOI] [PubMed] [PMC]

27.

Díaz C, Aragón N, Lopez-Medina E, Arango MC, Dávalos D, Contreras-Rengifo A. Craniofacial and dental features in children aged 3–5 years with congenital Zika syndrome. Clin Oral Investig. 2023;27:5181–8. [DOI] [PubMed] [PMC]

28.

da Costa CCG, Dias VO, Martelli DRB, Marques NCT, Coletta RD, Júnior HM. First cases of oligodontia as a manifestation of the Zika virus congenital syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol. 2022;134:e261–6. [DOI] [PubMed]

29.

Gomes PN, do Amaral BA, Azevedo ID, de Medeiros Maia HC, Arrais NMR, de Lima KC. Association of congenital Zika syndrome with dental alterations in children with microcephaly. PLoS One. 2022;17:e0276931. [DOI] [PubMed] [PMC]

30.

de Oliveira AMM, de Melo EGM, Mendes MLT, Dos Santos Oliveira SJG, Tavares CSS, Vaez AC, et al. Oral and maxillofacial conditions, dietary aspects, and nutritional status of children with congenital Zika syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol. 2020;130:71–7. [DOI] [PubMed]

31.

Carvalho IF, Alencar PNB, Carvalho de Andrade MD, Silva PGB, Carvalho EDF, Araújo LS, et al. Clinical and x-ray oral evaluation in patients with congenital Zika virus. J Appl Oral Sci. 2019;27:e20180276. [DOI] [PubMed] [PMC]

32.

Silva LVO, Hermont AP, Magnani IQ, Martins CC, Borges-Oliveira AC. Oral alterations in children with microcephaly associated to congenital Zika syndrome: a systematic review and meta-analyses. Spec Care Dentist. 2023;43:184–98. [DOI] [PubMed]

33.

Paixao ES, Cardim LL, Costa MCN, Brickley EB, de Carvalho-Sauer RCO, Carmo EH, et al. Mortality from congenital Zika syndrome — nationwide cohort study in Brazil. N Engl J Med. 2022;386:757–67. [DOI] [PubMed] [PMC]

34.

Komarasamy TV, Adnan NA, James W, Balasubramaniam VR. Zika virus neuropathogenesis: the different brain cells, host factors and mechanisms involved. Front Immunol. 2022;13:773191. [DOI] [PubMed] [PMC]

35.

Polonio CM, de Freitas CL, Zanluqui NG, Peron JPS. Zika virus congenital syndrome: experimental models and clinical aspects. J Venom Anim Toxins Incl Trop Dis. 2017;23:41. [DOI] [PubMed] [PMC]

36.

Ventura CV, Maia M, Travassos SB, Martins TT, Patriota F, Nunes ME, et al. Risk factors associated with the ophthalmoscopic findings identified in infants with presumed Zika virus congenital infection. JAMA Ophthalmol. 2016;134:912–8. [DOI] [PubMed]

37.

Ficenec SC, Schieffelin JS, Emmett SD. A review of hearing loss associated with Zika, Ebola, and Lassa fever. Am J Trop Med Hyg. 2019;101:484–90. [DOI] [PubMed] [PMC]

38.

Aguiar RS, Pohl F, Morais GL, Nogueira FCS, Carvalho JB, Guida L, et al. Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome. Sci Signal. 2020;13:eaay6736. [DOI] [PubMed]

39.

Cobourne MT, Sharpe PT. Tooth and jaw: molecular mechanisms of patterning in the first branchial arch. Arch Oral Biol. 2003;48:1–14. [DOI] [PubMed]