Neuroretinitis: A Comprehensive Review

Neuroretinitis is characterized by optic disc edema with macular exudates in a star pattern, often unilateral, resulting from primary optic disc inflammation with secondary macular involvement.
Key clinical findings: Optic disc edema, macular star (lipid-rich exudates in Henle’s layer), subretinal fluid, and sometimes chorioretinal white spots or vitreous cells.
Subretinal fluid may precede macular star formation, caused by fluid passing through the external limiting membrane into the subretinal space.
Fundus autofluorescence: Macular star appears hypoautofluorescent due to blockage of retinal pigment epithelium by exudates.
Optical coherence tomography (OCT): Shows neurosensory retinal thickening, subretinal fluid, macular exudates, and flattening of the foveal contour. Spectral-domain OCT may reveal epipapillary infiltrates.

Neuroretinitis is a descriptive term, not tied to a single cause, with etiologies divided into infectious, inflammatory, autoimmune, and mimickers (optic disc edema with macular star, ODEMS).
Most common cause: Bartonella henselae (cat scratch disease, CSD), responsible for the majority of cases.
Other infectious causes: Tuberculosis, syphilis, toxoplasmosis, Lyme disease, and viral infections (e.g., herpes viruses).
Inflammatory causes: Sarcoidosis, Behçet’s disease, and idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome.
Autoimmune causes: Associated with immune checkpoint inhibitors, post-COVID-19 vaccination, paraneoplastic syndromes, and myelin oligodendrocyte glycoprotein-associated disease (MOGAD).
Mimickers (ODEMS): Hypertensive retinopathy, papilledema, anterior ischemic optic neuropathy (AION), epipapillary vitreous traction, optic disc tumors, and toxic optic neuropathies (e.g., from chemotherapy agents like bis-chlorethyl-nitrosourea).

Epidemiology: Incidence of CSD is 3–4 per 100,000 in the U.S., with 60% of cases in individuals under 18 years, highest risk in children aged 5–10.
Transmission: Primarily via cat scratches or bites, with cat fleas (Ctenocephalides felis) as the main vector. Other vectors include ticks, biting flies, and possibly dogs.
Pathogenesis: B. henselae is a fastidious, gram-negative, haemotropic bacillus that establishes intra-erythrocytic bacteremia. It uses type IV secretion systems to invade host cells, avoiding lysosomal degradation, and promotes angiogenesis via vascular endothelial growth factors.
Ocular manifestations (5–10% of CSD cases):
- Most common: Optic disc edema (88% of cases), with 64% presenting with a macular star, 15% developing it later, and 21% without a macular star (cat scratch optic neuropathy, CSON).
- Other findings: Parinaud oculoglandular syndrome (follicular conjunctivitis with regional lymphadenopathy), focal/multifocal retinitis, choroiditis, uveitis, retinal vascular occlusions, and bacillary angiomatosis (more common in immunocompromised patients).
Systemic symptoms (70% of neuroretinitis cases): Flu-like illness (67%), fever (28%), headaches (23%), and ocular pain (11%).
Immunocompromised patients: More severe ocular findings (e.g., retinal bacillary angiomatosis, subretinal vascular masses) and systemic manifestations (e.g., culture-negative endocarditis, bacillary peliosis).

History is critical: Inquire about cat exposure (especially kittens), recent travel, tick exposure, sexual history, and systemic symptoms (e.g., fever, lymphadenopathy, joint pain).
Intravenous fluorescein angiography (IVFA): Shows late leakage from the optic disc vasculature, confirming proteinaceous leakage as the cause of macular exudates.
OCT: Essential for documenting central macular thickness, retinal thickness, and subretinal fluid height, aiding in monitoring disease progression.
Laboratory tests for B. henselae: Serology (IgM/IgG), polymerase chain reaction (PCR), or enzyme-linked immunosorbent assay (ELISA) to confirm CSD.
Neuroimaging (MRI): May show optic nerve enhancement in B. henselae-associated neuroretinitis, helping differentiate it from other optic neuropathies.

Hypertensive retinopathy: Bilateral, with cotton-wool spots, hemorrhages, and arteriolar attenuation.
Papilledema: Bilateral, associated with enlarged blind spot and MRI findings of raised intracranial pressure.
AION: Unilateral, with a small “disc-at-risk” in the fellow eye and systemic risk factors (e.g., hypertension, diabetes).
Multiple sclerosis (MS): Unlikely to cause neuroretinitis, as MS targets the myelin sheath, not optic disc vasculature. Acute papillitis with a macular star is rare in MS.

B. henselae-associated neuroretinitis:
- Often self-limited in immunocompetent patients, resolving over weeks to months.
- Antibiotics (controversial benefit): Doxycycline (100 mg BID for 4–6 weeks) or azithromycin (500 mg on day 1, then 250 mg daily for 4 days) may be considered, especially in severe cases or immunocompromised patients.
- Corticosteroids: May be used adjunctively in severe cases with significant vision loss, but evidence is limited.
Idiopathic recurrent neuroretinitis:
- Characterized by recurrent episodes with no identifiable cause.
- Treatment: Immunosuppressive therapy (e.g., corticosteroids, azathioprine) to reduce recurrence and preserve vision.
Mimickers: Treat underlying cause (e.g., blood pressure control for hypertensive retinopathy, intracranial pressure management for papilledema).

Immunocompetent patients: Generally benign, with most ocular manifestations resolving spontaneously.
Immunocompromised patients: Higher risk of severe, vision-threatening complications requiring aggressive treatment.
Recurrent idiopathic neuroretinitis: May lead to progressive visual loss due to repeated episodes.