Early-onset high myopia and underlying disease

Paper title: Aetiology, characteristics and workup of early onset high myopia

Authors: Son H-S (1,2), Zeng A (3), Jacobsen VP (4), Welk G (4), Niknahad A (5), VandeLune J (4), Bragg TL (4), Zhao L (5), Ruggeri ML (2,6), Drack AV (4), Dumitrescu AV (4), Doyle JJ (7,3)

1. University Eye Clinic Heidelberg, Heidelberg, Germany 
2. Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA 
3. Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA 
4. Ophthalmology and Visual Sciences, University of Iowa Health Care, Iowa City, Iowa, USA 
5. Johns Hopkins School of Medicine, Baltimore, Maryland, USA 
6. Gabriele d’Annunzio University of Chieti and Pescara, Chieti, Abruzzo, Italy 
7. Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA 

Date: Published online February 26, 2026

Reference: Son HS, Zeng A, Jacobsen VP, Welk G, Niknahad A, VandeLune J, Bragg TL, Zhao L, Ruggeri ML, Drack AV, Dumitrescu AV, Doyle JJ. Aetiology, characteristics and workup of early onset high myopia. Br J Ophthalmol. 2026 Feb 26:bjo-2025-329097

[Link to abstract]

Early-onset high myopia (eoHM) is often associated with underlying ocular and systemic disease. Associated conditions can include inherited retinal disorders, connective tissue diseases, chromosomal anomalies, and ocular developmental abnormalities. However, the relative prevalence and clinical characteristics of these conditions in real-world practice are not well defined. Distinguishing associated from isolated eoHM in clinical practice can also be challenging, particularly in young children with limited history or symptoms.

This retrospective cohort study analysed 407 patients with eoHM seen at two tertiary eye centres in the United States between 2012 and 2022. eoHM was defined as myopia requiring correction at ≤2 years of age or ≤−6.00D by 6 years. Patients underwent varying levels of ocular, systemic and genetic workup to identify associated conditions and assess the usefulness of different tests for identifying underlying conditions.

Key points were as follows.

• Of 407 patients with eoHM, 60% had an associated disorder (39% ocular, 21% systemic), while 40% were classified as isolated; associated cases more often presented earlier with features such as nystagmus and reduced visual acuity. 
• Children presenting before age 1 were five times more likely to have associated disorders; nystagmus increased likelihood fivefold
• Connective tissue disorders and inherited retinal disorders were associated with more severe (≤−9.00D) and symmetric myopia, while retinopathy of prematurity and glaucoma showed greater asymmetry. 
• Electroretinography (ERG) was abnormal in 97% of inherited retinal disorder cases, often detecting disease even when OCT findings were normal, while genetic testing identified pathogenic variants in 78% of tested cases. 
• In isolated eoHM, imaging abnormalities were uncommon and largely related to myopic structural changes such as posterior staphyloma.

This study shows that early-onset high myopia (at least 6D of myopia before age 6) is not, in a majority of cases, due to a simple refractive cause. It also highlights that many cases are associated with underlying ocular or systemic disease, and that key clinical features can help guide when further investigation or referral is needed. 

Children presenting with high myopia in the first year of life, or before age 3, are more likely to have an associated condition. The presence of nystagmus, reduced visual acuity, or atypical visual behaviour should prompt further investigation. Symmetry and severity of myopia can also provide useful clues. Very high (greater than 9D) and symmetrical myopia may suggest inherited retinal or connective tissue disorders, while marked asymmetry may point towards local ocular pathology.

Importantly, routine examination alone may not detect all underlying causes. Electroretinography (ERG) is particularly useful for identifying inherited retinal disorders such as congenital stationary night blindness, where retinal structure (such as macular OCT) may appear normal despite significant functional abnormality. In these cases, genetic testing can help confirm the diagnosis, guide prognosis and support appropriate counselling.

In practice, this supports a lower threshold for referral or further investigation in young children with high myopia, particularly when red flags are present. Early diagnosis can guide clinical decisions, enable genetic assessment for the patient and their family, and ensure best-practice ocular and systemic health management management.

This study provides valuable real-world data, but several limitations should be considered. As a retrospective analysis from two tertiary centres, the cohort likely includes more complex or atypical cases, which may overestimate the prevalence of associated disorders compared to primary care settings. Variation in clinician-led workup also means that not all patients underwent the same investigations, particularly electroretinography and genetic testing, which may have led to underdiagnosis in those classified as isolated.

The findings also highlight gaps in current diagnostic pathways. Many widely used investigations, such as OCT, showed limited sensitivity for detecting underlying genetic or retinal conditions. In contrast, electroretinography and genetic testing were more useful for identifying these conditions, although access to these tests remains variable across different healthcare settings.

Further prospective studies are needed to define more consistent workup approaches and to evaluate cost-effectiveness in different clinical contexts. There is also a need for research into management strategies, including the role and effectiveness of myopia control interventions in children with associated ocular or systemic conditions, and whether slowing myopia progression alters visual or ocular health prognosis in these complex cases. 

Background: Early-onset high myopia (eoHM) associates with multiple ocular and systemic disorders. This study evaluates the repertoire and relative prevalence of these disorders in a tertiary care setting, parses them by eoHM and other characteristics and evaluates the utility of diagnostic workup.

Methods: We performed a retrospective analysis of eoHM cases seen at two US eye centres from 2012 to 2022. eoHM was defined as a myopic refraction requiring glasses when ≤2 years of age and/or a refraction greater than -6D by 6 years of age. We reviewed the extent and outcome of workup, including ocular examination, imaging, electrophysiology, systemic evaluation and genetic testing.

Result: Of 407 patients with eoHM, 39% had an associated ocular disorder, 21% had a systemic disorder and 40% had apparently isolated eoHM (ie, no associated condition). Patients with associated disorders often reported typical presenting complaints but were more likely to be seen earlier in life, to possess severe, symmetric or very asymmetric eoHM and to display other stigmata of visual dysfunction. Patients with connective tissue disorders and select inherited retinal disorders had the most severe and symmetric eoHM compared with other conditions or isolated cases. Electroretinography and genetic testing were critical workup components.

Conclusions: eoHM frequently associates with a wide array of ocular and systemic disorders and may display distinct clinical characteristics depending on the associated condition. Awareness of the range of disorders that present with eoHM, key distinguishing characteristics, the role of timely and targeted workup and the importance of an accurate diagnosis are key considerations.

[Link to abstract]