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Getting to the Cause of Unexplained Vision Loss in Children

By Michael J. Wan, MD, FRCSC

Vision loss is a common reason for children to present to both pediatric and comprehensive ophthalmologists. While the majority of cases are due to benign conditions, several blinding and even life-threatening diseases can initially present with unexplained vision loss. In order to efficiently diagnose and manage unexplained vision loss in children, it is important to have a thorough understanding of potential causes and a structured approach to the assessment. This issue of Ophthalmology Rounds summarizes the most common etiologies and methods for identifying them.

 

When a child presents with unexplained vision loss, it is crucial to have a systematic approach to guide the assessment. The majority of cases are due to benign and treatable conditions, such as refractive error, amblyopia, and functional vision loss. However, serious disorders of the retina, optic nerve, and central nervous system can present with similar signs and symptoms.

 

History

Obtaining a history for a child with vision loss often requires the integration of 2 stories: the patient’s and the caregiver’s. In older children, ask about the visual changes they have noticed and if there is something they think might help; eg, children who report vision loss because they want glasses will tell you if you ask. In younger children, it is helpful to have a mental framework of how poor vision will manifest at different ages.[1,2] It is also important to obtain a detailed birth history and family history. If the birth history is significant for prematurity, ask about screening and treatment for retinopathy of prematurity (ROP) which can be associated with subtle structural abnormalities.[3,4] A positive family history of vision loss increases the likelihood of a genetic disorder and the pattern of inheritance can help to narrow the differential diagnosis.

 

Examination

Checking vision

Although it may sound obvious, the first step in the assessment of a child with reported visual loss is to confirm that there truly is vision loss. To obtain an accurate measurement of visual acuity (VA), the testing method has to be appropriate for the child’s age and stage of visual and cognitive development (Table 1).[5] Otherwise, there is a significant risk of making an unjustified diagnosis of vision loss.[6] As a general rule, vision is best checked using the most advanced testing method the child can perform confidently. However, using an overly advanced testing method will be frustrating and may cause the vision to appear to be worse than it actually is.

Table 1: Visual acuity testing method by age

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

In addition to testing VA, it is also useful to look for signs of poor vision. Signs in infants include roving eye movements, nystagmus, and eye rubbing (oculodigital sign).[7,8] In young children, signs of poor vision may manifest differently depending on whether the vision loss is central or peripheral. Loss of peripheral vision can lead to apparently poor coordination, with the child tripping and running into things. Loss of central vision may manifest as the child getting extremely close to objects of interest. Keep in mind that these behavioural signs are often present to varying degrees in children with normal visual function.

 

Pupils

Checking pupils is relatively straightforward in children and can provide crucial information in certain cases of unexplained vision loss. In patients with severe vision loss due to congenital retinal or optic nerve disorders, the pupils are generally sluggish or poorly reactive. In contrast, the pupillary light reflex is usually normal in patients with cortical visual impairment. A paradoxical pupillary reaction (ie, initial constriction of pupils to darkness) is a specific sign that is associated with congenital causes of poor vision, most notably achromatopsia and congenital stationary night blindness (CSNB).[9] However, detecting a paradoxical pupillary reaction in an infant can be challenging in a typical clinical setting. The presence of a relative afferent pupillary defect is a highly sensitive test for unilateral (or asymmetric) optic nerve disease. Conditions such as optic nerve hypoplasia may be surprisingly difficult to see on fundus examination, while other conditions such as optic neuritis may have no abnormal fundus findings. Therefore, the pupils should always be checked prior to dilation in children with unexplained vision loss.

 

Sensorimotor examination

An assessment of both motor and sensory function in children is an indispensable part of the investigation of unexplained vision loss. The motor examination involves testing ocular alignment and extraocular motility in all cardinal positions of gaze. It is important to check alignment at both distance and near, as a deviation may be present in one and not the other. For instance, convergence insufficiency is an exo-deviation only at near that causes visual blurring with reading. The presence of strabismus, or any motility disorder, greatly increases the likelihood of vision loss due to underlying amblyopia. However, while strabismus is a common cause of vision loss, it can also be caused by vision loss (ie, sensory esotropia or exotropia). Strabismus that is acquired later in childhood generally causes diplopia, but this may also present as “vision loss” as children often have difficulty describing double vision.

 

The sensory examination tests the state of the binocular visual system. The Worth 4 Dot test for fusion and the Titmus test for stereoacuity are widely available and easily performed. These tests can also be very useful in uncovering functional vision loss.

 

Refraction

Cycloplegic refraction is essential in all children with vision loss as refractive error and amblyopia are, by far, the most common causes of visual impairment in children.10 Cycloplegia can be achieved in the majority of children with 1% cyclopentolate, but 1% atropine may be required in dark irises (eg. given twice daily for 3 days prior to the appointment). If the patient reports blurriness only at near, measure accommodative amplitude (eg. with dynamic refraction) prior to cycloplegia to check for accommodative insufficiency.

 

Ancillary testing

 

Depending on the examination findings, ancillary testing is often useful in determining the underlying etiology. The most used tests for vision loss in children include:

  • Visual field testing: important in any case of suspected intracranial disease or retinal dystrophy

  • Electroretinogram (ERG): diagnostic in cases of inherited retinal dystrophy

  • Visual evoked potentials (VEP): can detect optic nerve disease and test for visual potential in cortical visual impairment

  • Optical coherence tomography (OCT): useful in detecting structural abnormalities of the optic nerve and macula

 

Amblyopia/Refractive Error

On a population level, refractive error and amblyopia make up over 90% of visual impairment in children.[10] Amblyopia is defined as a loss of vision due to an abnormal visual experience early in life and is characterized by the loss of best-corrected VA in a structurally normal eye (or if there is underlying disease, vision loss that is out of keeping with the pathology). Amblyopia is the most common cause of monocular vision loss in children and affects 2%–4% of the population overall.[11,12]

 

Due to the high incidence of refractive error and amblyopia, a cycloplegic refraction (and manifest refraction if possible) should always be performed in a child with vision loss. Any significant refractive error should be corrected with glasses and the vision rechecked after a trial of full-time glasses wear. Bilateral high refractive error can cause amblyopia, although the degree of ametropia required to cause amblyopia is uncertain and probably varies between individuals. The American Academy of Ophthalmology provides guidelines of hyperopia >5 diopters, myopia >6 diopters, or astigmatism >2 diopters as risk factors for amblyopia.[13] In practice, it is advisable to correct smaller amounts of refractive error if the child’s vision is subnormal and no other cause is identified.

 

Anisometropia (asymmetric refraction between the eyes) is a common cause of monocular vision loss due to amblyopia. Similar to ametropia, the exact amount of anisometropia required to cause amblyopia is not ­definitively known. In practice, even small differences in refraction warrant full-time refractive correction if there is associated vision loss. If the amblyopia is not severe (ie, vision >20/100 in the affected eye), it is reasonable to start with full-time glasses wear for a few months before commencing with further amblyopia therapy, as approximately 27% of moderate amblyopia cases will completely resolve with refractive correction alone.[14]

 

In rare cases, a child may be found to have consistently decreased vision with no pathology and no amblyogenic risk factors. In these cases, it is possible that a ­transient amblyogenic factor early in life caused amblyopia and then resolved (eg, lid swelling, vitreous hemorrhage). This is strictly a diagnosis of exclusion once all other potential causes have been ruled out. These patients should be started on standard amblyopia therapy as their vision may improve. It is also important to continue to follow in case there is an underlying condition which manifests later in life.[15,16]

 

Retinal Diseases

Several retinal disorders can present as unexplained vision loss in children. Infants with signs of significant vision loss despite a normal ocular structural examination and no neurological disease (eg, cerebral palsy) should be strongly suspected of having an inherited retinal dystrophy.

 

Leber congenital amaurosis (LCA) is an autosomal-recessive severe retinal dystrophy which usually presents in the first year of life with roving eye movements, nystagmus, poor pupillary responses, and a characteristic oculodigital sign (eye poking, pressing, and rubbing).[8] The fundus appears normal initially, but affected individuals often develop pigmentary retinopathy later in life. Other congenital retinal dystrophies can also present with unexplained vision loss, although the degree of vision loss is typically less severe. Retinal dystrophies that primarily affect the cone system (eg, achromatopsia) present with nystagmus, photophobia, poor colour vision, and reduced VA.[17] Retinal dystrophies that primarily affect the rod system (eg. CSNB) present with nystagmus, nyctalopia, poor peripheral vision, and mildly reduced VA with normal colour vision. In general, inherited retinal dystrophies are diagnosed by obtaining an ERG. With the continued evolution of genetic testing, many of the responsible genes are now identifiable. While not mandatory, genetic testing can provide important prognostic information for the patient, allow for genetic counselling for the parents, and facilitate enrolment in ongoing gene therapy trials.

 

Stargardt disease is the most common inherited dystrophy affecting the central retina, usually presenting later in childhood with unexplained vision loss.[18] Typical findings include yellow pisciform flecks, which change over time, and retinal pigment epithelium (RPE) changes in the macula. During the course of the disease, affected patients typically develop bull’s eye maculopathy and atrophic macular degeneration (Figure 1A). However, in the early stages of the disease, the retinal findings are subtle and easily missed. While fluorescein angiography may show the classic silent choroid (due to accumulation of lipofuscin), fundus autofluorescence (FAF) can also show early changes in Stargardt disease and is easier to perform in children. With FAF, active flecks have increased autofluorescence and RPE atrophy within the macula appears as an area of decreased autofluorescence (Figure 1B). Full-field ERG is usually normal in Stargardt disease, but a multifocal ERG and genetic testing can be confirmatory.

Figure 1
A: Fundus photo of Stargardt disease showing early signs of atrophic maculopathy.
B: Fundus autofluorescence showing decreased autofluorescence in the macula.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Other uncommon retinal disorders are also diagnostic considerations in a child with unexplained vision loss. Autoimmune retinopathy presents with retinal thinning on OCT, ERG abnormalities and positive antiretinal antibodies.[19] Acute macular neuroretinopathy is a post-viral condition that causes mildly reduced VA and subtle reddish-brown perimacular retinal lesions on examination.[20] Isolated foveal hypoplasia may be subtle on fundus examination (Figure 2A) but has a characteristic appearance on OCT (Figure 2B).[21]

 

 

Figure 2

A: Fundus photo showing the subtle lack normal foveal architecture and no foveal reflex.

B: Optical coherence tomography (OCT) clearly showing foveal hypoplasia.

 

 

 

 

 

 

 

 

Optic Nerve

A number of inherited and acquired optic nerve diseases can present as unexplained vision loss in childhood. The most common congenital optic nerve disorder is optic nerve hypoplasia. This condition is characterized by a small optic nerve surrounded by a hypopigmented scleral ring, known as the “double ring” sign (Figure 3).[22] However, on fundus examination, the outer scleral ring can look like the border of a normal optic nerve with the small hypoplastic nerve appearing to be the optic cup (Figure 3). Predilation pupillary examination can be hugely helpful in these cases. Optic nerve hypoplasia will generally cause sluggish pupils when bilateral and a relative afferent pupillary defect when unilateral, alerting the examiner to the presence of pathology. It is crucial to diagnose optic nerve hypoplasia as early as possible because associated endocrine and neurological abnormalities can cause severe cognitive delay or even death if not recognized and treated at an early age. Therefore, all patients with optic nerve hypoplasia (bilateral or unilateral) require neuroimaging and an endocrinology workup.

Figure 3: Fundus photos showing a right hypoplastic optic nerve with the “double ring” sign, and a normal left optic nerve.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hereditary optic neuropathies are another important cause of unexplained vision loss in childhood. Dominant optic atrophy is the most common hereditary optic neuropathy and presents with insidious vision loss during the first decade of life.22 VA ranges widely from near-normal to legally blind.[23] Almost all patients have a colour vision deficiency, central scotoma on visual field testing, and characteristic (but not patho­gnomonic) focal or wedge-shaped temporal pallor of the optic nerves (Figure 4). Given the autosomal dominant inheritance pattern, family history and examination of the parents can be useful. OCT is also valuable in demonstrating thinning of the retinal nerve fibre layer, particularly temporally.[24] The ­diagnosis can usually be confirmed by genetic testing as a mutation in the OPA1 gene is responsible for 75% of cases.[25]

 

Figure 4: Fundus photos showing a wedge of temporal optic nerve pallor in a patient with dominant optic atrophy. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Another common hereditary optic neuropathy is Leber hereditary optic neuropathy (LHON). Patients with LHON usually present between the ages of 15–35 years with subacute, painless, central vision loss in one eye, followed by the fellow eye weeks to months later. Within a year of onset, >95% of affected patients have bilateral involvement with vision loss progressing to ≤20/200.[26] A triad of signs on fundus examination are characteristic of LHON: peripapillary telangiectatic vessels, swelling of the nerve fibre layer around the disc (pseudopapilledema), and absence of leakage on fluorescein angiography.[27] LHON is caused by mutations in mitochondrial deoxyribonucleic acid (mtDNA) and all affected females pass the mutation to their offspring. For unknown reasons, there is incomplete penetrance and 80%–90% of affected individuals are male.[28] In >90% of cases, genetic testing shows 1 of 3 point mutations in mtDNA: 11778 (70%), 14484 (14%), or 3460 (13%).[26] Spontaneous recovery is uncommon and, although there is no proven benefit, it has become common practice to recommend avoidance of substances that might stress ­mitochondrial energy production, such as tobacco and alcohol.

 

In older children with sudden unexplained vision loss, optic neuritis is high on the differential diagnosis. Children with optic neuritis are less likely than adults to have pain with eye movements and more likely to have bilateral involvement and optic nerve edema.[29] As with any optic nerve disease, the pupillary examination is key, as patients with unilateral or asymmetric optic neuritis will have a relative afferent pupillary defect. An urgent MRI should be ordered to confirm the diagnosis and to detect any associated demyelinating lesions, which may indicate a diagnosis of multiple sclerosis. Unlike adults, in whom treatment is elective, treatment with intravenous systemic steroids is considered the standard of care in children.

 

Central Nervous System

In developed countries, damage to the central nervous system is becoming one of the most common causes of long-term visual impairment.[30] Most children with cortical visual impairment (CVI) will have a known neurological insult such as hypoxic ischemic encephalopathy, cerebral vascular event, or meningitis.[31] The majority of children with CVI also have associated neurological findings such as cerebral palsy, seizures, or hemiparesis. However, some seemingly healthy children with unexplained vision loss are ultimately diagnosed with CVI.[32] Neuroimaging is required to establish the diagnosis, but a VEP can also be helpful in measuring reduced visual potential in a patient with a structurally normal ocular examination. After the diagnosis is made, an etiological factor such as sepsis or prolonged apnea is often identified retrospectively. This emphasizes the importance of a thorough history at presentation to identify potential neurological insults that could suggest an underlying diagnosis of CVI.

 

Although uncommon, intracranial tumours are a potentially life-threatening cause of unexplained vision loss. Suprasellar tumours such as gliomas, craniopharyngiomas, and pituitary adenomas can initially present with nonspecific visual symptoms.[33-35] On history, it is important to be attentive for associated signs and symptoms of a suprasellar tumour, such as severe headaches, short stature, or diabetes insipidus. In addition, any child with a known diagnosis of neurofibromatosis-1 or suggestive findings (eg, Lisch nodules) should be suspected of harbouring an optic pathway glioma. On examination, visual fields that demonstrate a homonymous or bitemporal hemianopsia should raise suspicion of an intracranial process. Band atrophy of the optic nerve is another ominous sign. However, children are often unable to perform formal visual field testing and may have no objective signs of pathology at presentation, so young children with unexplained vision loss should always be followed.

 

Functional Vision Loss

One of the most common causes of unexplained vision loss in children is functional vision loss (also known as psychogenic or nonorganic vision loss).[36] While many parents are relieved by a diagnosis of functional vision loss, others are confused or even angered by the suggestion that their child is “faking” it. For the physician, the diagnosis can be disconcerting because serious diseases can be missed in the early stages, and patients with proven functional vision loss can subsequently develop organic disease, which may lead parents to blame the physician for “missing” the diagnosis. Despite the challenges, every comprehensive and pediatric ophthalmologist will encounter functional vision loss in a child, and therefore needs to have an approach.

 

Children with functional vision typically present around the age of 9–11 years and there is a strong female preponderance.[37] It is important to note that, unlike adults, children with functional vision loss are usually not malingering (intentionally faking for secondary gain). These children are often preoccupied with their vision and genuinely believe that the symptoms are due to underlying disease. In some cases, children under psychological stress may present with vision loss due to a conversion disorder, which is the unconscious loss of vision for an unconscious secondary gain (eg, avoiding bullying at school).38 Finally, there is a group of patients who present with functional vision loss in association with organic disease. These patients have true vision loss but exaggerate the severity.[36]

 

The approach to functional vision loss requires 3 steps:

 

  1. Rule out organic causes of vision loss
     

  2. Demonstrate that the child’s vision is significantly better than reported
     

  3. Discuss the diagnosis with the patient and parents

 

During the assessment, there are often hints that the vision loss is functional. For instance, the child may seem excessively concerned with subtle visual changes or apathetic about seemingly severe vision loss. Parents may be overly invested in the visual disability or aggressive about the need for specific tests or treatments. During the examination, VA will often fluctuate dramatically between appointments. In addition, the child will often read hesitantly with exaggerated signs of effort, even when the letters are easily within the range of reported vision.

 

When functional vision loss is suspected, many methods are available to try to prove that the vision is better than reported. For severe monocular vision loss, the Worth 4 Dot is useful as very few children will deduce that the right eye should see 2 red lights and the left eye should see 3 green lights. Stereoacuity can be helpful as children with 40 arcsec of stereoacuity (9/9 circles on the Titmus stereoacuity test) have vision of ≥20/40 in both eyes.[39] It can be helpful to “trick” the child into demonstrating normal vision on the distance letter acuity chart. One effective method is to put up the phoropter with plano lenses, turn the room lights down to remove external cues, start from the smallest letters (20/10) and move up the chart very slowly.36 Compared to the 20/10 letters, the 20/20 or 20/25 letters look so large that the child will often read these letters without difficulty. If the parents are in the room and trying to read the letters themselves, they will usually realize that the vision is much better than reported.

 

The management of functional vision loss is, to a great extent, a matter of personal preference. As a general rule, it is important to reassure the parents and child that the visual system is structurally normal. A follow up in a few months is advisable to ensure that the vision has indeed improved and no signs of organic disease have developed. Fortunately, with reassurance, most children will spontaneously recover over time. One notable exception is patients with unconscious secondary gain (conversion disorder) in whom the chance of recovery is much worse.[38] These patients may benefit from a referral to psychiatry, although the prognosis for visual recovery remains guarded.

 

Conclusion

Unexplained vision loss is a common and challenging issue for every ophthalmologist who sees children. It is crucial to be aware of the signs of vision loss and to be comfortable with vision testing methods for children of different ages. The differential diagnosis includes common conditions such as amblyopia and uncommon but serious disorders of the retina, optic nerve, and central nervous system. While assessing children can be challenging, using a structured approach with an understanding of the potential causes can help make vision loss in children a much less stressful, perhaps even enjoyable, condition to diagnose and treat.

 

Dr. Wan is an Assistant Professor, Department of Ophthalmology and Vision Sciences, University of Toronto, and a Pediatric Ophthalmologist, Sick Kids Hospital, Toronto, Ontario.

 

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Disclosure Statement: Dr. Wan has stated that he has no disclosures to report in association with the contents of this issue.

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