New Retinal Disorder Linked to Vision Loss in Children

A multicenter study led by researchers from the State Key Laboratory of Ophthalmology in China has identified a previously unrecognized retinal disorder in children following a febrile illness. The condition, termed Hyperacute Outer Retinal Dysfunction (HORD), is characterized by sudden bilateral vision loss, photoreceptor disruption, and variable recovery.

Key Findings: Sudden Vision Loss After Febrile Illness

The study, published in JAMA Ophthalmology, examined eight pediatric patients (16 eyes) between the ages of 3 and 7, all of whom experienced severe, sudden-onset vision loss approximately two weeks after a febrile illness.

Despite initial profound vision impairment, most patients demonstrated significant central vision recovery over the course of a year. However, retinal imaging and electrophysiological testing revealed persistent photoreceptor dysfunction, raising concerns about long-term visual outcomes.

Clinical Characteristics of HORD

• Symptoms at Onset:

• Severe bilateral vision loss

• Nyctalopia (night blindness)

• Visual field constriction

• Dyschromatopsia (color vision deficiency)

• Retinal Imaging Findings:

• Optical coherence tomography (OCT): Diffuse ellipsoid zone (EZ) and external limiting membrane (ELM) loss

• Early fundus examination: Largely unremarkable

• Macular Recovery: 75% and 88% of eyes showed EZ and ELM integrity restoration by one year

• Electroretinography (ERG) Results:

• Extinguished rod and cone responses, even in patients with improved visual acuity

Long-Term Outcomes and Recovery

• By Week 4:

• Early signs of macular recovery emerged.

• At One Year:

• 88% of patients (7 of 8) regained visual acuity of 20/40 or better, with 50% (4 of 8) achieving 20/25 or better.

• However, extrafoveal retinal regions remained affected in many cases.

Investigating the Cause: Immune-Mediated Mechanisms?

Comprehensive systemic evaluations did not identify any clear infectious or autoimmune triggers. However, two patients tested positive for specific antiretinal antibodies (anti-PKC γ and anti-Ri), raising the possibility of an immune-mediated pathology.

• Treatments Administered:

• Corticosteroids

• Intravenous immunoglobulin (IVIG)

• Methotrexate (in select cases)

• Despite treatment, the definitive therapeutic effect remained unclear.

How HORD Differs from Other Retinal Disorders

A commentary titled "Hyperacute Outer Retinal Dysfunction—A Retina on Fire" by Timothy Boyce and Ian Han from the University of Iowa suggests that HORD may represent a novel inflammatory-mediated retinal disorder, potentially involving an autoimmune encephalitis-like mechanism.

Comparisons with known retinal diseases:

• Unlike multiple evanescent white dot syndrome (MEWDS) or acute zonal occult outer retinopathy (AZOOR), HORD presents with:

• Severe bilateral involvement

• Only partial visual recovery

• While some features overlap with nonparaneoplastic autoimmune retinopathy (np-AIR), the pediatric onset and hyperacute progression make HORD distinct.

Future Directions: Research and Clinical Implications

Further studies are needed to:

• Determine the underlying cause of HORD

• Identify optimal treatment strategies

• Understand long-term visual prognosis

• Explore potential biomarkers, including novel antiretinal antibodies

This study introduces HORD as a potential new retinal disease entity, highlighting the need for further research into immune-mediated retinal dysfunctions in pediatric patients.

References:

Yizhe Cheng et al, Hyperacute Outer Retinal Dysfunction, JAMA Ophthalmology (2025). DOI: 10.1001/jamaophthalmol.2024.6372

Timothy M. Boyce et al, Hyperacute Outer Retinal Dysfunction—A Retina on Fire, JAMA Ophthalmology (2025). DOI: 10.1001/jamaophthalmol.2024.6488