Acute Idiopathic Maculopathy

Key points at a glance

Key Points at a Glance

• Acute Idiopathic Maculopathy (AIM) is an acute macular disease that suddenly occurs in young healthy individuals.
• It presents with acute severe vision loss (sometimes to 20/200 or worse) after flu-like prodromal symptoms.
• Coxsackievirus (hand-foot-and-mouth disease) is the most common causative virus; cases after COVID-19 infection or vaccination have also been reported.
• OCT shows BALAD (bacillary layer detachment) as a characteristic finding.
• Most cases recover spontaneously within weeks to months, but rarely complications such as choroidal neovascularization or macular hole may occur.
• The efficacy of steroid treatment is not established; the basic approach is observation and continuous OCT monitoring.

1. What is Acute Idiopathic Maculopathy?

Acute Idiopathic Maculopathy (AIM) is an acute macular disease that suddenly occurs in young to middle-aged healthy individuals. It was first reported in 1991 by Yannuzzi et al. as “Unilateral Acute Idiopathic Maculopathy (UAIM).” Subsequently, bilateral cases were reported, and in 1996 Freund reported bilateral cases, leading to the renaming to AIM.

Epidemiologically, it is more common in young to middle-aged Caucasians, with no clear gender difference. It is often preceded by flu-like prodromal symptoms such as fever, sore throat, and rash.

In a review of 90 cases by Jia et al. (2024), 78% had flu-like prodromal symptoms, 43% had fever, 22% had sore throat, and 12% had rash ²⁾. On the other hand, about 30% had no prodromal symptoms and were negative for viral antibodies ²⁾.

The main site of pathology is thought to be inflammatory occlusion of the choriocapillaris and damage to the RPE (retinal pigment epithelium). [See Section 6 for details on the pathogenesis.]

Q What is the difference between AIM and UAIM?

A

Initially, Yannuzzi et al. reported only unilateral cases and called it “UAIM (Unilateral AIM).” Later, bilateral cases were reported, and in 1996 it was renamed to “AIM.” Currently, both unilateral and bilateral cases are called AIM.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

• Acute vision loss: Often unilateral, can be severe with visual acuity of 20/200 or worse.
• Central scotoma: A subjective symptom directly reflecting macular pathology.
• Metamorphopsia: Visual distortion due to RPE/photoreceptor damage.
• Photopsia: Seen in some cases.
• Eye pain: Usually absent.

Clinical Findings

Findings differ significantly between the acute and recovery phases. The changes are shown below.

Phase	Fundus Findings	OCT Findings
Acute phase	Macular exudative detachment + RPE thickening	BALAD + subretinal fluid
Recovery phase	Bull’s eye pattern	EZ recovery + RPE degeneration

In the acute phase, irregular exudative neurosensory retinal detachment in the macula, gray-white to gray-yellow thickening at the RPE level, and subretinal deposits are observed. Rarely, intraretinal hemorrhage or papillitis may be present.

In the convalescent phase, a bull’s eye pattern may remain in the lesion area. RPE atrophy and depigmentation may persist permanently.

Jia et al. (2024) reported a case of highly symmetric simultaneous bilateral onset ²⁾.

3. Causes and Risk Factors

The causes of AIM are diverse. They are broadly divided into infection-related and non-infection-related categories.

Infection-related

Coxsackievirus: The most commonly reported association is with hand, foot, and mouth disease (HFMD). Cases of unilateral acute vision loss after adult HFMD have been reported. ⁵⁾

COVID-19-related: Onset after COVID-19 infection and after vaccination has been reported. ¹⁾⁴⁾ In a case that developed the day after the second dose of the Pfizer vaccine, molecular mimicry between the spike protein and RPE components has been proposed as a mechanism. ⁴⁾

Other viruses: Associations with yellow fever, West Nile virus, and Zika virus have also been reported. ¹⁾

Bacterial infection: An association with streptococcal pharyngitis has also been reported. ¹⁾

Non-infection-related / Idiopathic

Autoimmune mechanism: About 30% of cases show no prodromal symptoms or elevated viral antibodies, suggesting an autoimmune mechanism. ²⁾

Pregnancy-related: Cases have been reported in the first trimester and postpartum.

Coagulation abnormalities: Cases with elevated CRP (172.63 mg/L) and abnormal coagulation parameters have been reported, suggesting an association with inflammatory hypercoagulability. ²⁾

Unknown cause: About 30% resolve spontaneously without an identified cause. ²⁾

When to See a Doctor

If you experience sudden vision loss in one eye, see an ophthalmologist immediately. If vision loss occurs after flu-like symptoms or hand, foot, and mouth disease, this condition may be suspected. Visual symptoms after COVID-19 vaccination also require attention.

Q What is the relationship between hand, foot, and mouth disease and AIM?

A

Coxsackievirus, which causes hand, foot, and mouth disease (HFMD), is the most commonly reported cause of AIM. ⁵⁾ When adults contract HFMD, they may develop acute vision loss within a few days of onset. Direct infection of RPE cells by coxsackievirus is suggested to be involved in the pathogenesis.

4. Diagnosis and Examination Methods

The diagnosis of AIM is made by a combination of multimodal imaging. Each modality shows characteristic findings.

Optical Examinations

OCT: In the acute phase, RPE thickening, BALAD (bacillary layer detachment), and subretinal fluid are observed. ¹⁾⁵⁾ BALAD is a transient finding that disappears within 5–10 days of onset. ⁵⁾ In the recovery phase, recovery of the ellipsoid zone (EZ) is seen. ¹⁾

OCTA: Detects flow deficits in the choriocapillaris. ¹⁾²⁾⁵⁾ In the recovery phase, restoration of blood flow can be confirmed.

Retro-mode SLO: A non-invasive modality using near-infrared light (790 nm). It detects central white plaques, perifoveal granular changes, and choroidal structural abnormalities. ³⁾

Fluorescein Angiography Examinations

FA (Fluorescein Angiography): Shows hypofluorescence in the early phase and hyperfluorescence in the late phase (fluorescence reversal phenomenon). ⁵⁾ In the late phase, dye pooling in the BALAD area is observed.

ICGA (Indocyanine Green Angiography): Shows hypofluorescence throughout all phases, reflecting impaired choriocapillaris circulation. ¹⁾⁵⁾ The hypofluorescent area on ICGA is larger than the lesion area on FA. ⁵⁾

Fundus Autofluorescence (FAF): Shows hyperautofluorescence in the acute phase. ¹⁾³⁾ In the recovery phase, it changes to hypoautofluorescence.

The temporal changes of each imaging finding are shown below.

Test	Acute phase findings	Recovery phase findings
FA	Early hypofluorescence → late hyperfluorescence	Window defect
ICGA	Hypofluorescence in all phases	Reduction of hypofluorescent area
Fundus autofluorescence	Hyperautofluorescence	Hypoautofluorescence

Blood tests measure Coxsackie virus antibody titer, CRP, and coagulation parameters. They are useful for excluding infectious diseases and assessing inflammation.

Differential diagnosis

• Central serous chorioretinopathy (CSR): AIM shows irregular early hypofluorescence. This differs from the jet-type and diffuse-type leakage of CSR.
• Acute posterior multifocal placoid pigment epitheliopathy (APMPPE): Similar to AIM, but APMPPE is bilateral and characterized by multiple placoid lesions in the posterior pole.
• Vogt-Koyanagi-Harada disease (VKH): Characterized by fluorescein leakage from the optic disc and bilateral serous detachment.
• Choroidal neovascularization (CNV): Can be differentiated by ICGA.
• Acute retinal pigment epitheliitis (Krill disease): OCT shows main lesions in the interdigitation zone. ³⁾

Q How to differentiate AIM from APMPPE?

A

Both diseases occur after flu-like prodromal symptoms, and FA findings are similar. ¹⁾ However, AIM is usually unilateral and macular-limited, while APMPPE is bilateral with multiple placoid lesions in the posterior pole. The formation of a bull’s eye pattern during the recovery phase of AIM is also useful for differentiation. Recently, it has been suggested that AIM may belong to the same spectrum as APMPPE. ¹⁾

5. Standard Treatment

AIM is essentially a self-limiting disease, and observation is the standard management. Most cases recover spontaneously within weeks to months.

Observation

Continuous monitoring with OCT (every 4–6 weeks) is recommended. Indicators include EZ recovery, BALAD disappearance, and visual improvement.

Steroid Therapy

Opinions on steroid administration vary among reports.

In the case by Fan et al. (2024), all three episodes over 3 years showed rapid improvement with oral prednisone 60 mg ¹⁾. On the other hand, a retrospective analysis of 17 cases by Rosar et al. (2021) found no significant difference in visual prognosis between steroid-treated and untreated groups ²⁾.

Oral steroids may be considered when exudative findings are prominent, but since the disease is self-limiting, evaluating their true effect is difficult.

Other Treatments

• NSAIDs: Some cases have reported improvement with topical NSAIDs. ²⁾
• Anti-VEGF therapy: Indicated only when choroidal neovascularization is present. ²⁾

Complications to be aware of

AIM resolves spontaneously in most cases, but rarely complications such as choroidal neovascularization, macular hole, and subretinal fibrosis may occur, leading to poor visual prognosis. ²⁾ If secondary visual decline occurs, prompt evaluation for complications is necessary.

Q Is steroid treatment effective?

A

No conclusion has been reached. In the case by Fan et al., all three recurrences responded well to oral steroids. ¹⁾ However, in a retrospective analysis of 17 cases by Rosar et al., there was no difference in visual prognosis between the steroid-treated group and the natural course group. ²⁾ Since this disease resolves spontaneously, it is difficult to distinguish the true effect of steroids from the natural course.

6. Pathophysiology and detailed pathogenesis

Three hypotheses have been proposed for the pathogenesis of AIM.

Hypothesis 1: Primary choriocapillaritis

This hypothesis suggests that inflammatory occlusion of the choriocapillaris occurs primarily, leading to secondary RPE damage.

Anjou et al. (2022) reported that hypofluorescence on ICGA at all phases and blood flow defects on OCTA suggested inflammatory occlusion of the choriocapillaris. ⁵⁾ Fan et al. (2024) also showed that hypofluorescence on ICGA and blood flow defects on OCTA had the same distribution, supporting that choroidal ischemia is the cause of BALAD. ¹⁾

The proposed pathway is: choroidal circulation disorder → secondary RPE damage → breakdown of the outer blood-retinal barrier → subretinal fluid accumulation.

Hypothesis 2: Direct viral infection of RPE

This hypothesis suggests that coxsackievirus directly infects RPE cells (Huemer 1996), causing phagocytic dysfunction of photoreceptor outer segments, leading to exudative changes.

Hypothesis 3: Immune-mediated RPE damage

This theory assumes autoimmune RPE damage due to viral infection or molecular mimicry.

Hasegawa et al. (2022) proposed molecular mimicry between spike protein and RPE components, and an enhanced immune response after the second vaccination as the pathogenesis in AIM cases following COVID-19 vaccination. ⁴⁾ It has also been suggested that inflammatory cytokine release associated with viral infection induces RPE damage via endothelial injury and hypercoagulability. ²⁾

Mechanism of BALAD

BALAD is a transient finding that resolves within 5–10 days of onset. ⁵⁾ The following mechanisms have been proposed.

• Choroidal ischemia theory: Choroidal ischemia → photoreceptor stress → splitting at the inner segment myoid layer (Kohli hypothesis). ⁵⁾
• Fibrin adhesion theory: Inflammatory fibrin enhances adhesion between the RPE and interdigitation zone, causing separation at the weakest point (bacillary layer). ⁵⁾

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7. Latest Research and Future Perspectives (Investigational Reports)

For patients: Please read this

The following content is currently under investigation or in clinical trials and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

Relationship between AIM and the acute posterior multifocal placoid pigment epitheliopathy-serpiginous choroiditis spectrum

Fan et al. (2024) suggested that AIM may be part of the same spectrum as acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis. ¹⁾ They reported for the first time three episodes of recurrence over three years and asynchronous bilateral onset in the same patient, indicating that AIM can be a recurrent and bilateral disease. ¹⁾

New diagnostic approach using retro-mode SLO

Hande et al. (2026) reported the first application of retro-mode SLO to AIM. ³⁾ They showed that retro-mode SLO can depict persistent choroidal structural changes even after OCT normalization, suggesting that residual disease pathology undetectable by conventional modalities may be visualized. ³⁾

New findings on peripheral retinal vascular occlusion

Jia et al. (2024) reported a case of AIM complicated by peripheral retinal vascular occlusion. ²⁾ It was suggested that high CRP (172.63 mg/L) and coagulation parameter abnormalities may be involved in peripheral vascular occlusion, indicating that AIM can develop in the context of systemic inflammation and coagulation abnormalities. ²⁾

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8. References

1. Fan Y, Kroeger ZA, Flaxel CJ. Bilateral asynchronous acute idiopathic maculopathy with disease recurrence. Am J Ophthalmol Case Rep. 2024;36:102187.
2. Jia Y, Zhang H, Kang L, et al. A case of acute idiopathic maculopathy in both eyes with peripheral vascular occlusion. BMC Ophthalmol. 2024;24:498.
3. Hande P, Mishra S, Tendulkar K, et al. Multimodal Imaging in Acute Idiopathic Maculopathy: Insights from Retro-Mode Scanning Laser Ophthalmoscopy. J VitreoRetinal Dis. 2026.
4. Hasegawa T, Sannomiya Y, Toyoda M, et al. Acute idiopathic maculopathy after COVID-19 vaccination. Am J Ophthalmol Case Rep. 2022;26:101479.
5. Anjou M, Fajnkuchen F, Nabholz N, et al. Multimodal Imaging of Unilateral Acute Maculopathy Associated with Hand, Foot, and Mouth Disease: A Case Series. Case Rep Ophthalmol. 2022;13:617-625.