Neuroretinitis refers to inflammation of the optic disc that spreads to the macula via retinal nerve fibers. It is a general term for a syndrome presenting with optic disc edema and retinal inflammation due to idiopathic causes or infection by various pathogens.
In 1916, Leber first described it as “stellate maculopathy.” In 1977, Gass showed that disc edema precedes macular exudates and proposed the term “neuroretinitis.”
It can occur at any age, but the average age is around 25 years. The male-to-female ratio is 1:1.8, with a slight female predominance. In about 50% of cases, no cause is identified, and they are classified as idiopathic8).
Neuroretinitis is classified into the following three types:
Importantly, a diagnosis of neuroretinitis is not considered a risk factor for future development of multiple sclerosis (MS).
Neuroretinitis is different from demyelinating optic neuritis and is not considered a risk factor for developing multiple sclerosis. The presence of a macular star is a useful finding to rule out MS 8).
The initial symptom is blurred vision, which is usually painless. In less than 10% of cases, eye pain may also occur.
Most cases are unilateral. A relative afferent pupillary defect (RAPD) is often positive but not as prominent as in demyelinating optic neuritis. This is thought to be because the visual loss is due not only to optic nerve involvement but also to retinal (macular) involvement.
Optic disc edema is the earliest finding, and a macular star appears 1 to 2 weeks after the onset of visual loss 8). Before the macular star appears, only optic disc edema may be observed. Vitreous cells are present in about 90% of cases 7).
Acute Phase
Optic disc edema: The earliest finding. Fluorescein angiography shows diffuse leakage.
Peripapillary serous retinal detachment: Exudative serous detachment associated with disc edema.
Vitreous cells: Present in about 90% of cases. May be accompanied by anterior chamber cells and flare.
Macular edema: Appears 9–12 days after onset. Subsequently, hard exudates arrange in a star-shaped pattern.
Recovery phase
Resolution of macular star: Exudates become ill-defined and gradually disappear.
Resolution of optic disc edema: Disappears in 8–12 weeks, leaving a normal or pale optic disc.
Retinal pigment epithelial changes: Only RPE defects may remain.
Optic disc pallor: May lead to optic atrophy in chronic or recurrent cases.
Fluorescein angiography (FA) shows diffuse leakage from the optic disc, but no abnormalities in the retinal vessels themselves. This finding is “an ocular fundus finding easily mistaken for retinal disease,” but FA can confirm that leakage is only from the optic disc.
Optical coherence tomography (OCT) can detect retinal thickening, subretinal fluid, and exudates within the outer plexiform layer (Henle layer). It is also useful for early detection of serous retinal detachment before macular star formation.
That is correct. Optic disc edema precedes, and the macular star forms 1–2 weeks later 8). In cases with only disc edema at the initial visit, re-examination within 2 weeks should confirm the appearance of the star. In recurrent cases, the star may not show a typical pattern.
The causes of neuroretinitis are diverse. They are broadly divided into infectious and non-infectious.
| Category | Main causes |
|---|---|
| Bacterial | B. henselae, syphilis, tuberculosis, Lyme disease |
| Parasites and protozoa | Toxoplasma, Toxocara, Gnathostoma |
| Viruses | HSV, cytomegalovirus, EBV, measles, mumps |
The most common cause is cat scratch disease (CSD) caused by Bartonella henselae, which accounts for the majority of infectious neuroretinitis. More than 40% of patients have a history of owning a cat (especially a kitten), and papules or vesicles appear at the site of injury within a few days.
Other infectious causes include the following:
IRVAN syndrome (idiopathic retinal vasculitis, aneurysms, and neuroretinitis) is a rare clinical syndrome that includes neuroretinitis as one of its components6).
Risk factors are related to exposure to each pathogen. They include immunocompromised status, contact with animals (especially kittens), travel to endemic areas, and preference for raw food.
Cat scratch disease, the most common cause of neuroretinitis, is transmitted from cats (especially kittens) carrying Bartonella henselae. More than 40% of patients own cats. However, neuroretinitis due to B. henselae has also been reported in patients without cat contact5).
The combination of optic disc edema and macular star is a diagnostic clue. However, the macular star appears 1–2 weeks after onset, so only disc edema may be present at the initial visit8). It is important to take a history of animal contact, travel history, sexual activity, and preference for raw meat.
Basic examination items include visual acuity testing, color vision testing, pupillary evaluation (checking for RAPD), visual field testing (detection of central scotoma), and dilated fundus examination.
| Test | Main Findings |
|---|---|
| FA | Diffuse fluorescein leakage from the optic disc |
| OCT | Retinal thickening, subretinal fluid, OPL exudates |
| MRI | Usually normal (some cases show enhancement of intraocular optic nerve) |
The following tests are performed to differentiate infectious causes:
PCR testing of intraocular fluid is useful in atypical cases where serological tests are inconclusive. In a report by Alafaleq et al. (2025), Bartonella quintana was identified by PCR of vitreous fluid in a case of chronic uveitis that was not diagnosed by serology5).
Diseases presenting with macular star include hypertensive retinopathy, papilledema (increased intracranial pressure), anterior ischemic optic neuropathy (AION), and diabetic papillopathy. While many of these are bilateral, neuroretinitis is usually unilateral, which is useful for differentiation.
Treatment of neuroretinitis is directed at the underlying disease.
Cat Scratch Disease (CSD)
First-line: Rifampicin (10 mg/kg) + Sulfamethoxazole/Trimethoprim (TMP-SMX) for 3 weeks5)
Alternative: Ciprofloxacin 250 mg twice daily + Azithromycin 250 mg twice daily (for sulfa allergy)5)
Children: Azithromycin (due to contraindication of quinolones)5)
Spontaneous recovery: After treatment, 93% achieve final visual acuity of 0.5 or better.
Other Infections
Toxoplasma: SMX-TMP twice daily + Prednisolone. For persistent cases, intravitreal clindamycin 1 mg injection7)
Cytomegalovirus (immunocompromised): Intravitreal foscarnet 2.4 mg + Valganciclovir 900 mg twice daily2)
Syphilis: Penicillin G intravenous
Gnathostoma: Surgical removal of the worm + Albendazole 400 mg twice daily for 21 days4)
In the treatment of neuroretinitis due to cat scratch disease, the choice of antibiotics should be individualized based on age, allergy history, and severity5). Azithromycin has high intraocular penetration and is an effective option for both children and adults5).
There is no established treatment for idiopathic neuroretinitis1). Many cases show good visual recovery regardless of intervention.
Mizera et al. (2023) reported a case of recurrent idiopathic neuroretinitis in which maintenance therapy with mycophenolate mofetil 2 g/day plus prednisolone 10 mg/day led to a stable course without recurrence1). In this case, anti-MOG antibodies were weakly positive, but the clinical picture was atypical for MOGAD, and it was ultimately judged to be idiopathic.
Severe macular edema associated with neuroretinitis is rare but can be a major cause of central vision loss.
Aminuddin et al. (2024) reported a case of severe macular edema associated with neuroretinitis due to dual infection with Toxoplasma and HSV-1. They administered a single intravitreal injection of ranibizumab in addition to antibiotics, antivirals, and oral steroids, and observed a marked reduction in subretinal fluid within two weeks3).
Most cases of idiopathic neuroretinitis recover spontaneously. In 90% of reported cases, final visual acuity recovers to 0.5 or better. However, in cases with recurrent episodes, optic atrophy may progress, leading to insufficient recovery of visual acuity and visual field1). For recurrent cases, long-term immunosuppressive therapy is considered.
The essence of neuroretinitis is inflammation of the optic disc vasculature and fluid exudation into the peripapillary retina. The mechanism is as follows:
In infectious neuroretinitis, the pathogen either directly invades the optic nerve or activates autoimmunity against the optic nerve, triggering vasculitis. Bartonella species have the ability to invade vascular endothelial cells, and this property is thought to cause various ocular findings such as peripapillary vasculitis, retinitis, and choroiditis5).
In idiopathic cases, an autoimmune reaction following viral infection is presumed. The fact that more than 50% of cases are preceded by influenza-like prodromal symptoms supports this hypothesis.
In neuroretinitis caused by Gnathostoma, it is inferred that larvae enter the eye via the ciliary circulation and cause fibrous proliferation and hemorrhage around the optic disc4).
PCR testing of intraocular fluid is gaining attention as a powerful diagnostic approach for atypical cases that are difficult to diagnose with conventional serological tests.
Alafaleq et al. (2025) analyzed 5 Bartonella-positive cases among 1854 uveitis patients and identified Bartonella quintana DNA by LightCycler PCR of vitreous fluid in a 71-year-old chronic posterior uveitis case with negative serology5). PCR testing was reported to be particularly useful in atypical ocular bartonellosis and cases where the cause is obscured by steroid treatment.
Multiple reports have described the efficacy of intravitreal drug administration for refractory cases.
Hsu et al. (2022) reported that in a case of toxoplasmic neuroretinitis unresponsive to SMX-TMP plus oral steroids, an additional intravitreal injection of clindamycin 1 mg resulted in complete recovery of visual acuity to 20/20 within one month 7).
In Case 3 of Alafaleq et al. (2025), for bilateral posterior uveitis resistant to steroid therapy for six months, an intravitreal injection of gentamicin 1 mg was administered, and in combination with systemic antibiotics, resolution of microaneurysms and exudates was observed 5). However, final visual acuity remained at 20/63 (right eye) and 20/200 (left eye).
Aminuddin et al. (2024) reported the efficacy of intravitreal ranibizumab for severe macular edema associated with dual infection, but the efficacy of anti-VEGF agents for neuroretinitis has not been established 3).
