Restricted accessResearch articleFirst published online 2025
Cortical Visual Impairment Across a Range of Neurodevelopmental Disorders: Clinical Characterization,Diagnostic Tool Evaluation,and Association with Developmental Outcomes
Cortical visual impairment is particularly relevant in children with neurodevelopmental disorders yet remains underdiagnosed. This study assessed the prevalence and severity of cortical visual impairment in 4 neurogenetic conditions: STXBP1, SLC6A1, Ring 14, and 8p-related disorders. We also evaluated the CDKL5-Clinical Severity Assessment–Clinician vision subdomain as a diagnostic tool and examined the association between cortical visual impairment and developmental outcomes. A retrospective chart review of 85 patients found cortical visual impairment in 44%, most commonly in 8p (54%) and STXBP1 (50%); no cases were seen in SLC6A1. The CDKL5-Clinical Severity Assessment–Clinician vision subdomain effectively distinguished cortical visual impairment cases (mean score 25.9 vs 2.6, P < .0001). A cutoff score ≥11 showed high specificity (95.9%) and positive predictive value (94.3%). Cortical visual impairment was significantly associated with greater developmental impairment, with higher overall CDKL5-Clinical Severity Assessment–Clinician scores and lower Vineland Adaptive Behavioral Scales–Third Edition scores. Early identification of cortical visual impairment is critical for ensuring access to appropriate therapies and therefore should be more systematically evaluated for in neurogenetic conditions.
KranBSLawrenceLMayerDLHeidaryG. Cerebral/cortical visual impairment: a need to reassess current definitions of visual impairment and blindness. Semin Pediatr Neurol. 2019;31:25‐29. doi:https://doi.org/10.1016/j.spen.2019.05.005
2.
WilliamsCPeaseAWarnesP, et al.Cerebral visual impairment-related vision problems in primary school children: a cross-sectional survey. Dev Med Child Neurol. 2021;63(6):683‐689. doi:https://doi.org/10.1111/dmcn.14819
3.
Sandfeld NielsenLSkovLJensenH. Visual dysfunctions and ocular disorders in children with developmental delay, I: prevalence, diagnoses and aetiology of visual impairment. Acta Ophthalmol Scand.2007;85(2):149‐156. doi:https://doi.org/10.1111/j.1600-0420.2006.00867.x
4.
ChangMYMerabetLB. Special commentary: cerebral/cortical visual impairment working definition: a report from the National Institutes of Health CVI Workshop. Ophthalmology. 2024;131(12):1359‐1365. doi:https://doi.org/10.1016/j.ophtha.2024.09.017
5.
Roman-LantzyC. Cortical Visual Impairment: An Approach to Assessment and Intervention. American Foundation for the Blind; 2007.
6.
McConnellELSaundersKJLittleJA. What assessments are currently used to investigate and diagnose cerebral visual impairment (CVI) in children? A systematic review. Ophthalmic Physiol Opt. 2021;41(2):224‐244. doi:https://doi.org/10.1111/opo.12776
7.
ChoiSAKimYO. West syndrome with hyperkinesia and cortical visual impairment: a case report of GRIN1 encephalopathy. J Genet Med. 2021;18(1):55‐59. doi:https://doi.org/10.5734/JGM.2021.18.1.55
8.
BoschDGMBoonstraFNde LeeuwN, et al.Novel genetic causes for cerebral visual impairment. Eur J Hum Genet.2016;24(5):660‐665. doi:https://doi.org/10.1038/ejhg.2015.186
9.
MorelliFAprileGMartoliniC, et al.Visual function and neuropsychological profile in children with cerebral visual impairment. Children (Basel). 2022;9(6):921. doi:https://doi.org/10.3390/children9060921
10.
BenkeTADemarestSAngioneK, et al.CDKL5 deficiency disorder. GeneReviews®[Internet]. 2024.
11.
BrockDFidellAThomasJJuarez-ColungaEBenkeTADemarestS. Cerebral visual impairment in CDKL5 deficiency disorder correlates with developmental achievement. J Child Neurol. 2021;36(11):974‐980. doi:https://doi.org/10.1177/08830738211019284
12.
LehmanSSYinLChangMY. Diagnosis and care of children with cerebral/cortical visual impairment: clinical report. Pediatrics. 2024;154(6):e2024068465.
13.
HuoRBurdenSKHoytCSGoodWV. Chronic cortical visual impairment in children: aetiology, prognosis, and associated neurological deficits. Br J Ophthalmol. 1999;83(6):670‐675. doi:https://doi.org/10.1136/bjo.83.6.670
14.
BoonstraFNBoschDGGeldofCJStellingwerfCPorroG. The multidisciplinary guidelines for diagnosis and referral in cerebral visual impairment. Front Hum Neurosci.2022;16:727565.
OkurVHammLKavusH, et al.Clinical and genomic characterization of 8p cytogenomic disorders. Genet Med. 2021;23(12):2342‐2351. doi:https://doi.org/10.1038/s41436-021-01270-2
17.
SaldarisJWeisenbergJPestana-KnightE, et al.Content validation of clinician-reported items for a severity measure for CDKL5 deficiency disorder. J Child Neurol. 2021;36(11):998‐1006. doi:https://doi.org/10.1177/08830738211019576
18.
SaldarisJMJacobyPDownsJ, et al.Psychometric evaluation of clinician- and caregiver-reported clinical severity assessments for individuals with CDKL5 deficiency disorder. Epilepsia. 2024;65(10):3064‐3075. doi:https://doi.org/10.1111/epi.18094
HarrisPATaylorRMinorBL, et al.The REDCap consortium: building an international community of software platform partners. J Biomed Inform.2019;95:103208. doi:https://doi.org/10.1016/j.jbi.2019.103208
21.
HarrisPATaylorRThielkeRPayneJGonzalezNCondeJG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform.2009;42(2):377‐381. doi:https://doi.org/10.1016/j.jbi.2008.08.010
22.
UnalI. Defining an optimal cut-point value in ROC analysis: an alternative approach. Comput Math Methods Med. 2017;2017:3762651. doi:https://doi.org/10.1155/2017/3762651
23.
BoschDGBoonstraFNde LeeuwN, et al.Novel genetic causes for cerebral visual impairment. Eur J Hum Genet. 2016;24(5):660‐665. doi:https://doi.org/10.1038/ejhg.2015.186
24.
SonksenPMDaleN. Visual impairment in infancy: impact on neurodevelopmental and neurobiological processes. Dev Med Child Neurol. 2002;44(11):782‐791. doi:https://doi.org/10.1017/s0012162201002936
25.
ChadhaRKSubramanianA. The effect of visual impairment on quality of life of children aged 3-16 years. Br J Ophthalmol. 2011;95(5):642‐645. doi:https://doi.org/10.1136/bjo.2010.182386
26.
MatsubaCAJanJE. Long-term outcome of children with cortical visual impairment. Dev Med Child Neurol. 2006;48(6):508‐512. doi:https://doi.org/10.1017/s0012162206001071
27.
LehmanSSYinLChangMY; Section on Ophthalmology; Council on Children With Disabilities; American Association for Pediatric Ophthalmology and Strabismus, American Academy of Ophthalmology; American Association of Certified Orthoptists.Diagnosis and care of children with cerebral/cortical visual impairment: clinical report. Pediatrics. 2024;154(6):e2024068465. doi:https://doi.org/10.1542/peds.2024-068465
28.
RehRKDiasBGNelson 3rdCA, et al.Critical period regulation across multiple timescales. Proc Natl Acad Sci U S A.2020;117(38):23242‐23251. doi:https://doi.org/10.1073/pnas.1820836117
29.
ChangMYBorchertMS. Advances in the evaluation and management of cortical/cerebral visual impairment in children. Surv Ophthalmol. 2020;65(6):708‐724. doi:https://doi.org/10.1016/j.survophthal.2020.03.001
30.
van GenderenMDekkerMPilonFBalsI. Diagnosing cerebral visual impairment in children with good visual acuity. Strabismus. 2012;20(2):78‐83. doi:https://doi.org/10.3109/09273972.2012.680232
31.
MancusoMHouldenHMolnarMJ, et al.How to approach a neurogenetics diagnosis in different European countries: the European Academy of Neurology Neurogenetics Panel survey. Eur J Neurol. 2022;29(7):1885‐1891. doi:https://doi.org/10.1111/ene.15320
