Myopia and amblyopia are among the most common conditions in pediatric ophthalmology practice. While the diagnoses are relatively easy and the conditions are treatable, knowing when to suspect an underlying cause or a genetic disorder contributing to myopia or masquerading as amblyopia is less clear. Here, I’ll discuss some of the signs and clues for cases where myopia and amblyopia are manifestations of a more severe condition.

Myopia

We know that myopia can result from an elongated axial eye length, an abnormal intraocular lens, an abnormal corneal curvature or a combination. Usual symptoms are decreased distance vision, squinting—or adopting a head position for distance viewing—for pinhole purposes. Some children can be asymptomatic, and the suspicion arises during vision screening. 

The final diagnosis is made with an eye exam and cycloplegic refraction. The treatment is glasses or contact lenses. Most children will tolerate the correction and will have normal visual acuity with correction. A certain degree of progression of the myopic correction is expected in most children, and using diluted atropine drops, glasses with peripheral defocus, and special contact lenses (orthoK) can mitigate myopia progression in most patients. 

Amblyopia

Amblyopia represents decreased vision in one or both eyes due to abnormal vision development in infancy or childhood. The most common cause of amblyopia is uncorrected refractive error in one or both eyes, resulting in poor development of the visual function in the affected eye(s). Another common cause is strabismus or eye misalignment, in which the two eyes aren’t used simultaneously. Rarely, a structural anomaly that impairs vision, such as visually significant eyelid ptosis, media opacity, cataract or corneal scar, is the cause of amblyopia. 

In all these situations, addressing the cause of amblyopia (with glasses and/or surgery) and using the penalization of the better-seeing eye (with patching or atropine) or binocular stimulation treatments (NovaSight or Luminopia) improves vision. Each treatment modality has its indications and limitations but is effective when applied correctly. (To learn more about binocular stimulation treatments, check out “New Ways to Address Amblyopia” from the February issue of Review.)

Going Beyond the Surface

Myopia and amblyopia can sometimes be associated with ocular or systemic conditions or be symptoms of an underlying condition. Rapid myopia progression, i.e., progression greater than 1 D per year in older children or 2 D or more per year in younger children, raises a red flag. It’s common to recheck vision and refraction in one year for older children and in six months for younger children. If there’s progression of 1 D or more in those six months, progression is considered rapid.

Be on guard for amblyopia cases in which the patient’s vision is out of proportion to expectations for amblyopia. Examples include four or more lines of difference in vision for a minimum of anisometropia (0.5 D) or a patient with intermittent exotropia or monofixation syndrome. If no other signs are present, standard treatment is recommended first. If the patient fails to improve as expected (i.e., vision improves with glasses and/or patching or atropine), additional work-up should be considered for an underlying condition.

When your suspicion is raised, consider these conditions:

• Retinopathy of prematurity. Especially when requiring laser therapy, ROP is commonly associated with developing progressive high myopia with debut in infancy. The prevalence of myopia seems to vary with the severity of ROP, reported in 0 percent to 16 percent of preterm infants with no ROP and up to 21 percent to 100 percent for children whose ROP was treated with laser photocoagulation.¹

Retinopathy of prematurity is often associated with the development of progressive high myopia. Photo: Science Source.

• Juvenile and congenital glaucoma. These are both associated with childhood myopia. In patients with primary congenital glaucoma, myopia correlates with IOP and cup-to-disc ratio.² Approximately 70 to 80 percent of patients with juvenile primary open-angle glaucoma are myopic at presentation, and myopia less than -1 D correlates with disease progression.³

• Inherited retinal dystrophies. Dystrophies like congenital stationary night blindness (CSNB) present with early childhood myopia with rapid progression with a normal fundus exam and a normal optical coherence tomography. Children will usually not complain of night blindness (because they have no comparison). Parents may not recognize that children have difficulties with dark adaptation unless pointed out or asked specific questions. In some cases, a history of improved or resolved early childhood nystagmus can be elicited from parents.

• Connective tissue disorders. Disorders such as Stickler Syndrome, Marfan, Knobloch, Wagner syndrome, etc., can present with early onset progressive high myopia and/or subluxation of the intraocular lenses before other systemic symptoms are noted.

• Other retinal dystrophies. Dystrophies like Leber congenital amaurosis associated with RPE65, X-linked retinitis pigmentosa associated with RPGR variants, and many others can be associated with progressive high myopia. Retinal dystrophies affecting bipolar cells and cones seem to be more commonly associated with early-onset progressive myopia.⁴

• Chromosomal abnormalities. Like Down syndrome, other chromosomal issues can be associated with high myopia.

The diagnostic workup differs with the condition, however, and might include full-field electroretinogram (pathognomonic for retinal dystrophies), macula optical coherence tomography (retinal dystrophy, foveal hypoplasia), and ultimately genetic testing with pre- and post-test counseling.

Consequences

In the majority of these cases, the myopic refractive error starts early in childhood and tends to progress, resulting in high myopia in childhood. Depending on the underlying condition and the magnitude of myopia, there’s an increased risk of retinal detachment primarily associated with trauma but also nontraumatic.⁵ It’s unclear if the mechanism of myopia development is the same in these conditions as in “regular myopia” and if the same progression mitigation methods are effective. The studies that show the efficacy of diluted atropine and peripheral defocus lenses didn’t include (or analyzed separately) children with high myopia associated with an underlying condition.

Conditions like optic pathway gliomas associated with neurofibromatosis type I, slow-growing intracranial or orbital tumors, unilateral or asymmetric optic nerve hypoplasia, inherited optic neuropathies (Leber hereditary optic neuropathy or Dominant optic atrophy), or retinal conditions with onset in later childhood (like Stargardt disease) can present with asymmetric decreased vision and strabismus that can be diagnosed as amblyopia when clinical findings are subtle or absent. Bilateral amblyopia secondary to high refractive errors or deprivation is possible, but vision should improve with timely and correct treatment.

When an underlying condition is present, visual loss tends to be progressive or doesn’t respond to treatment as expected. Failure to improve or worsening vision in the amblyopic eye with reported good compliance with treatment should raise concerns. Some children develop new symptoms like acquired nystagmus, behavioral abnormalities, headaches or seizures that can be missed while focusing on the eye exam, glasses prescription and amblyopia treatment.

The diagnostic workup differs for each condition; however, it might include brain and orbit MRI, optic nerve and/or macula OCT and genetic testing. Family history, review of systems, complete physical and ocular exam, and a high index of suspicion and awareness can help initiate the workup and diagnose an underlying condition associated with myopia or masquerading as amblyopia. A complete and correct diagnosis may change the treatment and the visual and overall prognosis for patients and families.

The Bottom Line

While most childhood myopia cases are considered “simple myopia” and have a relatively benign course, certain features may suggest an underlying genetic disorder:

• Early onset. Myopia that presents in early childhood, particularly requiring correction before age 6, may indicate a genetic disorder.

• High myopia. Severe myopia with high refractive values at onset or rapidly progressive early in life may also be associated with underlying genetic disorders.

As with myopia, certain features of amblyopia may suggest an underlying genetic disorder:

• Severe. Amblyopia that is more severe than expected for the risk factor may indicate an underlying disorder.

• Refractive to treatment. Amblyopia that’s not responding as expected to adequate therapy may indicate an underlying disorder.

• Bilateral. Bilateral amblyopia may suggest there’s an underlying genetic disorder causing the high refractive error or the deprivation, driving inadequate response to therapy. Examples include oculocutaneous albinism associated with high hyperopia or myopia, and congenital cataracts associated with systemic conditions (e.g., PAX6-related disorders).

Dr. Collinge is an assistant professor in the Department of Pediatrics of the University of Connecticut School of Medicine. 
She can be reached at jcollinge@connecticutchildrens.org. She has no financial interest in any of the products discussed in the article. Dr. Dumitrescu is an associate professor of ophthalmology and pediatrics at Carver College of Medicine in Iowa City and the chair of the genetic eye disorder committee of AAPOS. She has no related financial disclosures. 

^{1. Quinn GE, Johnson L, Abbasi S. Onset of retinopathy of prematurity as related to postnatal and postconceptional age. Br J Ophthalmol 1992;76:5:284-8.} 

^{2. Sihota R, Sidhu T, Agarwal R, Sharma A, Gupta A, Sethi A, et al. Evaluating target intraocular pressures in primary congenital glaucoma. Indian J Ophthalmol 2021;69:8:2082-7.}

^{3. Gupta S, Singh A, Mahalingam K, Selvan H, Gupta P, Pandey S, et al. Myopia and glaucoma progression among patients with juvenile onset open angle glaucoma: A retrospective follow up study. Ophthalmic Physiol Opt 2021;41:3:475-85.} 

^{4. Hendriks M, Verhoeven VJM, Buitendijk GHS, Polling JR, Meester-Smoor MA, Hofman A, et al. Development of refractive errors: What can we learn from inherited retinal dystrophies? Am J Ophthalmol 2017;182:81-9.} 

^{5. Cheung N, Lee SY, Wong TY. Will the myopia epidemic lead to a retinal detachment epidemic in the future? JAMA Ophthalmol 2021;139:1:93-4.}