At the recently held 5th World Congress of Paediatric Ophthalmology & Strabismus (WCPOS V 2024) in Kuala Lumpur, Malaysia, delegates were treated to a session on ocular signs in pediatric patients that may indicate serious underlying systemic diseases.
The Ocular Signs that Saves Lives symposium was a melting pot of insights, with global experts delving into the complexities of systemic disorders and their ocular manifestations. Through engaging case studies and in-depth discussions, the speakers shared their expertise on the intricacies of detecting these conditions, emphasizing the critical role of family history, genetic testing and retinal imaging.
Small eyes, big problems
Dr. Brenda Bohnsack (USA) was first to take the podium with a comprehensive presentation on the microphthalmia-anophthalmia-coloboma (MAC) spectrum and its life-threatening associations.
“A lot of the time [MAC] findings have systemic associations,” Dr. Bohnsack explained, citing examples like neurologic abnormalities, congenital heart diseases, and genitourinary anomalies caused by genetic disorders, congenital infections and vitamin deficiency.
She stressed the significance of a thorough medical history and the potential necessity for genetic testing. “As ophthalmologists, we may be some of the first people these babies see,” Dr. Bohnsack reminded the audience, urging them to consider systemic associations and make appropriate referrals, underscoring the crucial role ophthalmologists play in early detection of serious diseases.
Metabolic crystals
Next, Dr. Susmito Biswas (United Kingdom) explored how signs in the anterior segment of the eye can signal bigger health issues. He explained that about one-third of inherited metabolic diseases have ocular features, with 30% showing anterior segment signs and 50% affecting the posterior segment.
In his lecture, Dr. Biswas shared detailed case studies, discussing the underlying diseases, their ocular signs, and treatments. One notable case involved a child with Wolman disease, caused by biallelic variants in the LIPA gene. This disease is characterized by crystals in the peripheral cornea and changes in the posterior lens capsule, along with adrenal calcification. “If left untreated, it can cause death,” Dr. Biswas cautioned.
He emphasized the importance of considering the overall health and family history of the infant or child, which should prompt clinicians to refer for metabolic workups and potentially life-saving treatments. Whole genome sequencing, if available, can also provide additional definitive diagnoses.
Flipping the script
Hannah Scanga, MS (United Kingdom) took over the podium next and delivered her lecture on ocular signs of two genetic diseases: multisystemic smooth muscle dysfunction syndrome (MSMDS) and thoracic aortic aneurysm dissection (TAAD).
MSMDS, an autosomal dominant disorder, presents ocularly as congenital mydriasis. Ms. Scanga explained, “The hotspot within the ACTA2 gene causes this exact phenotype, affecting smooth muscle cells and, specifically, the pupillary sphincter.”
Similarly, iris flocculi, associated with ACTA2 and MYH11 genes, can indicate TAAD. Like the speakers before her, Ms. Scanga stressed the importance of genetic testing and comprehensive evaluations for those at risk, noting, “It may seem like the family history is negative, but actually there just wasn’t anybody expressing it enough from a vascular standpoint.”
Ms. Scanga then posed an intriguing question. If families who have TAAD are found to have iris flocculi, “Can we use it as a predictor to say, “Is somebody [in the family] going to be at risk for these conditions as well?’”
Ms. Scanga has begun an exploration of this line of thought. Her team’s research found that all three children with congenital mydriasis in their study had MSMDS, with two testing positive for ACTA2 mutation. However, no children with iris flocculi showed variations from the ACTA2 gene.1
Despite these findings in children with iris flocculi, Dr. Scanga continues to recommend genetic testing. “The benefit-to-risk ratio from doing a genetic test for one or two genes outweighs the risk of missing this when the family history looks negative.”
Genetic counseling and risk assessment are crucial for identifying at-risk relatives. “So it’ll help us make sure that we’re taking care of not just our patients, but the family,” Ms. Scanga concluded.
From eyes to colon
Dr. Amgad Eldib (Egypt) shifted the spotlight to congenital hypertrophy of the retinal pigment epithelium (CHRPE) and its link to colorectal cancer.
CHRPEs, which are lesions at the retinal pigment epithelial level, are relatively common. “Some studies estimate them to be present in about one third of the population,” noted Dr. Eldib.
The concern lies in the correlation between CHRPE and familial adenomatous polyposis (FAP), an autosomal dominant condition that almost always leads to colorectal cancer if untreated.
Identifying risk in children can be tricky. Dr. Eldib emphasized paying attention to multiple, bilateral lesions, which are more strongly associated with FAP. He reassured that typical, well-circumscribed lesions and discrete “bear track” lesions are generally not linked to the APC gene associated with FAP. Additionally, the absence of CHRPE does not rule out FAP, complicating risk identification.
For a more accurate diagnosis, Dr. Eldib recommended getting a detailed family history, as well as combining fundus exams with genetic testing for APC gene mutations. He noted, “This approach may yield a higher accuracy in identifying patients at risk for FAP,” before opening the floor for questions.
Fields of gold
Next, Dr. Naomi Tan (United Kingdom) explored the impact of brain injuries on ganglion cells. When the brain is damaged, the axons of the ganglion cells can atrophy—a process known as transsynaptic axonal degeneration.
Dr. Tan highlighted the importance of optical coherence tomography (OCT) in identifying these changes. “On OCT, you can see the filling of the ganglion cell layer. We know this because experiments in primates have shown that removing the visual cortex leads to ganglion cell loss in the retina. We also know that peroneal brain injuries can cause optic disc atrophy and disc changes,” he said.
She emphasized that spotting these changes requires careful segmentation of the macular ganglion cell layer, which takes only about 60 seconds. Dr. Tan described the appearance as a “donut ring of golden color,” which she dubbed “fields of gold.”
To illustrate, Dr. Tan shared a case from her practice involving a 17-year-old treated for a high-grade glioma. The patient had a homonymous hemianopia and complained of tunnel vision and reading difficulties. Although his macula and retinal nerve fiber layer appeared normal, the segmented OCT images revealed a “hemi donut” pattern in the ganglion cell layer, indicating a significant visual field defect.
The “hemi donut” pattern in the ganglion cell layer on segmented OCT images.
For young patients, Dr. Tan stressed the importance of recognizing these signs on OCT in the absence of a visual field test—an examination easily performed on adults, but much more challenging with children. Ending her lecture, however, she cautioned, “This is not a sensitive test for brain tumors. While helpful to recognize it if you see it, do further investigation even in the presence of a normal ganglion cell layer.”
8 signs in 8 minutes
Dr. Karthikeyan Arcot Sadagopan (India) rounded out the symposium with a quick rundown of eight ocular signs in eight minutes. In the spirit of keeping things short and sweet, here’s a snapshot of what he covered:
- Renal coloboma disc may indicate papillorenal syndrome.
- Jaundice, posterior embryotoxon and optic disc drusen are symptoms of Alagille syndrome.
- Malignant hypertension might be due to pheochromocytoma.
- Pigmentary retinal degeneration and dystonia could indicate pantothenate kinase-associated neurodegeneration (PKAN).
- Heterogeneous pigmentation of hair, skin and iris is highly correlated with Hermansky-Pudlak Syndrome (HPS).
- Ocular ptosis and presence of lisch nodules is linked to Horner syndrome.
- Increasing esophoria for distance could be an early sign of sixth nerve palsy.
- Presence of angioid streaks is associated with higher incidence of pseudoxanthoma elasticum (PXE) and Paget’s disease of bone.
Dr. Sadagopan wrapped up his talk with a thought-provoking remark: “The eye only sees what the mind knows.” Ophthalmologists can only identify underlying conditions if they’re aware of the link to ocular signs, know what to look for and perform the necessary diagnostic tests.
Reference
- Taubenslag KJ, Scanga HL, Huey J, et al. Iris anomalies and the incidence of ACTA2 mutation. Br J Ophthalmol. 2019;103(4):499-503.
Editor’s Note: Reporting for this article occurred at the 5th World Congress of Paediatric Ophthalmology & Strabismus (WCPOS V 2024) from 11-13 July in Kuala Lumpur, Malaysia.
