Optic papillitis

Optic papillitis is inflammation of the optic nerve head, the intraocular segment visible on fundoscopy, and it is a subtype of optic neuritis in which disc swelling accompanies the acute attack, in contrast to retrobulbar neuritis, where the disc looks normal at onset.

It accounts for about 1 to 5 cases of optic neuritis per 100,000 person-years, peaks at 20 to 40 years of age with a female predominance, and about half of adults with a first demyelinating episode develop multiple sclerosis within 15 years.

Terminology and classification

• Optic papillitis is inflammation of the optic nerve head, the intraocular portion of the optic nerve that is visible on fundoscopy.
• It is a subtype of optic neuritis and is distinguished from retrobulbar neuritis, in which the inflammation lies behind the globe and the disc initially looks normal.
• The older terms intraocular optic neuritis and orbital optic neuritis describe the same anatomical distinction.
• Papillitis must not be confused with papilloedema, which is disc swelling caused by raised intracranial pressure rather than by inflammation of the nerve.
• ICD-10 codes the condition within the optic neuritis category H46, and the MONDO concept MONDO:0006879 and the DOID identifier DOID:10175 provide cross-database mapping.
• Some authors reserve the term papillitis for cases with visible disc swelling, and the term is used inconsistently in the literature.
• Paediatric papillitis is often post-infectious and may be bilateral, whereas adult papillitis is usually unilateral and linked to demyelinating disease.

History

• Clinical description became possible after Helmholtz invented the ophthalmoscope in 1851, which allowed direct visualisation of the optic disc.
• Nineteenth-century observers distinguished disc swelling from optic nerve atrophy, and the term papillitis was used for inflammatory swelling.
• In the early twentieth century retrobulbar neuritis was separated from papillitis, largely on the basis of a normal-appearing disc.
• The association between optic neuritis and multiple sclerosis was documented in the 1930s and confirmed by large cohort studies in the 1980s.
• The Optic Neuritis Treatment Trial, published in 1992, randomised 448 patients and established the standard use of intravenous methylprednisolone.
• In the 1990s Bartonella henselae was recognised as a cause of neuroretinitis and papillitis in children with cat contact.
• The discovery of aquaporin-4 antibodies in 2004 and myelin oligodendrocyte glycoprotein antibodies in the 2010s separated neuromyelitis optica and MOG antibody disease from multiple sclerosis.

Epidemiology

• Optic neuritis has an incidence of about 1 to 5 per 100,000 person-years, and papillitis accounts for the subset in which the disc is swollen.
• The peak age is 20 to 40 years in adults, with a female to male ratio of about 2 to 1.
• In children the mean age is around 10 years, papillitis is more common than retrobulbar disease, and bilateral involvement occurs in up to half of cases.
• About 50 percent of adults with a first episode of optic neuritis develop multiple sclerosis within 15 years, and the risk is higher when brain magnetic resonance imaging shows demyelinating lesions.
• The incidence increases with latitude, and the condition is more common in northern Europe and North America than in tropical regions.
• Bilateral simultaneous optic neuritis should prompt testing for neuromyelitis optica spectrum disorder, MOG antibody disease or a toxic and nutritional cause.
• Most epidemiological data come from the Optic Neuritis Treatment Trial, national registries and neuromyelitis optica cohorts, and paediatric estimates remain imprecise.

• Paediatric optic neuritis has an annual incidence of about 0.2 per 100,000 children in North American and European series, and papillitis accounts for a larger share of cases than in adults.

Pathophysiology

• Optic neuritis is an immune-mediated demyelinating disorder of the optic nerve in which T cells and antibodies target myelin and oligodendrocytes.
• In papillitis the inflammatory focus lies at the lamina cribrosa, and impaired axonal transport produces disc oedema and hyperaemia.
• In retrobulbar disease demyelination occurs behind the globe, so the disc is normal at onset and may later show pallor.
• Aquaporin-4 antibodies in neuromyelitis optica bind astrocytic water channels and cause complement-mediated damage that extends beyond myelin.
• MOG antibodies in MOG antibody disease target myelin oligodendrocyte glycoprotein and produce severe, often bilateral, optic neuritis with disc swelling.
• Bartonella henselae causes neuroretinitis through a combination of vasculitic and inflammatory mechanisms, often with a macular star.
• Axonal loss continues after the acute attack, and retinal nerve fibre layer thinning on optical coherence tomography correlates with persistent visual deficit.

Clinical features

• Visual loss develops over hours to days, is usually unilateral in adults and is often described as a central blur or fog.
• Pain on eye movement is characteristic, particularly in retrobulbar disease, and it precedes or accompanies the visual loss.
• Colour vision is disproportionately affected, and patients report that red appears washed out or grey.
• A central or centrocaecal scotoma is typical, and visual field testing may show a nerve fibre bundle defect.
• The disc is swollen, hyperaemic and has blurred margins in papillitis, sometimes with peripapillary haemorrhage or exudate.
• A relative afferent pupillary defect, the Marcus Gunn pupil, is expected in unilateral disease and helps distinguish papillitis from papilloedema.
• Vision worsens with heat or exercise in the Uhthoff phenomenon, and many patients report glare and reduced contrast sensitivity.

Diagnosis

• Diagnosis is based on the clinical picture and fundoscopy, supported by formal visual acuity, colour vision and visual field testing.
• Pupillary testing for a relative afferent pupillary defect should be performed in every suspected case.
• Optical coherence tomography shows thickening of the retinal nerve fibre layer acutely and thinning after recovery, and it is increasingly used as an outcome measure.
• Magnetic resonance imaging of the orbits with fat suppression shows nerve enlargement and enhancement, and brain imaging identifies demyelinating lesions that predict multiple sclerosis.
• Lumbar puncture and cerebrospinal fluid analysis may show pleocytosis, raised protein or oligoclonal bands and help exclude infection.
• Serological testing should be guided by the history and may include Bartonella henselae, aquaporin-4, MOG, syphilis and Borrelia burgdorferi.
• Differential diagnosis includes papilloedema from raised intracranial pressure, non-arteritic and arteritic anterior ischaemic optic neuropathy, Leber hereditary optic neuropathy, toxic and nutritional optic neuropathy, compressive lesions and central serous chorioretinopathy.

Management

• The Optic Neuritis Treatment Trial showed that intravenous methylprednisolone, 1 gram daily for three days followed by an oral taper, speeds visual recovery but does not change final visual outcome.
• Oral prednisone alone at the doses used in that trial increased the risk of recurrent optic neuritis and should not be used as monotherapy.
• Underlying infection is treated specifically, with azithromycin or doxycycline for Bartonella henselae and appropriate antimicrobial therapy for syphilis or Lyme disease.
• Neuromyelitis optica and MOG antibody disease are treated with high-dose intravenous steroids, and plasma exchange is used when steroids fail.
• Long-term immunosuppression with azathioprine, mycophenolate, rituximab or eculizumab is used in neuromyelitis optica to prevent relapses and blindness.
• Patients with a first demyelinating event and magnetic resonance imaging lesions may be offered disease-modifying therapy for multiple sclerosis after specialist assessment.
• Supportive care includes pain management, low vision aids and counselling about the usually favourable prognosis, since most patients recover to 20/40 or better.

• For aquaporin-4-positive neuromyelitis optica, eculizumab was approved by the United States Food and Drug Administration in 2019, and satralizumab and inebilizumab were approved in 2020 to reduce relapse-related blindness.

Research and controversies

• The role of steroids in optic neuritis remains debated, because the Optic Neuritis Treatment Trial found faster recovery without a long-term visual benefit.
• The dose, route and taper of corticosteroids vary widely between centres, and no trial has established the optimal regimen.
• Testing for aquaporin-4 and MOG antibodies has changed management, but access and turn-around time remain barriers in many settings.
• Optical coherence tomography and visual evoked potentials are being evaluated as surrogate endpoints for neuroprotection trials.
• Neuroprotective strategies, including phenytoin, erythropoietin and neurofilament light chain monitoring, have shown promise in early trials but not consistent benefit.
• Paediatric optic neuritis lacks large randomised trials, and treatment protocols are largely extrapolated from adult studies.
• Misdiagnosis as papilloedema or as functional visual loss delays appropriate treatment, and educational efforts to improve disc assessment are needed.