Bilateral asynchronous acute idiopathic maculopathy with disease recurrence

Abstract

Purpose

Acute idiopathic maculopathy (AIM) is a posterior segment disorder that involves the neurosensory retina, retinal pigment epithelium, and choroidal circulation. When first described, the disease was classified as unilateral, but subsequent reports have found bilateral presentations. There is growing evidence to suggest the coxsackie virus as the etiology, however, other pro-inflammatory conditions have also been temporally linked to fundoscopic findings. We report on a young male without viral prodrome and without known contact with viral illnesses who experienced bilateral recurrent acute idiopathic maculopathy.

Observations

A 35-year-old male presented with retinal whitening within the macula of the right eye. Multimodal imaging demonstrated a bacillary layer detachment, late leakage, and disruption of the choriocapillaris. Laboratory workup for inflammatory and infectious etiologies was negative. A diagnosis of AIM was made. The findings resolved with a steroid course. Nine months after initial presentation, the patient developed similar symptoms, fundoscopic, and imaging findings in the left eye, which again resolved with a steroid course. Three years after initial presentation, he developed symptoms in the right eye. Fundoscopy and imaging demonstrated a larger affected area compared to the prior episode. At his last follow up, the visual acuity, fundoscopy, and imaging findings had returned to baseline with no residual acuity deficit.

Conclusions and importance

The patient presented has recurrent, bilateral AIM. Bilateral presentations and recurrent presentations have previously been reported, but this case is unique as it meets both criteria. Based on multimodal imaging throughout each episode, we hypothesize that AIM may be on the white dot disease spectrum.

1. Introduction

Acute idiopathic maculopathy (AIM) is an exudative maculopathy characterized by acute onset, central vision loss. AIM was first described as unilateral acute idiopathic maculopathy (UAIM) by Yannuzzi et al in 1991, in a case series of 9 young adult patients (average age 32 years) with severe unilateral central vision loss, many with a documented prodromal flu-like illness. Characteristic exam findings of affected eyes in this case series included irregular exudative macular detachment overlying an area of sub-retinal thickening at the level of the retinal pigment epithelium (RPE). In most cases, patients achieved spontaneous and rapid improvement in visual acuity to 20/25 or better with associated resolution of the exudative changes.¹ A subsequent larger case series of UAIM patients expanded on this clinical spectrum, finding cases associated with eccentric macular lesions sparing the fovea (with generally better presenting visual acuity), papillitis, bilaterality, and subretinal exudation associated with a grayish to fluffy white appearance.² Therefore, the initialism of UAIM was dropped in favor of AIM. Recent case reports have further expanded the clinical spectrum to include episodes of recurrence.^3,4

The underlying etiology of AIM remains unknown, yet the term “Coxsackie Retinitis/Retinopathy” due to the presence of IgM or IgG titers present at the time of diagnosis has been used.⁵ However, no causal link has been established. In fact, AIM has also been associated with other viral and bacterial illnesses, such as yellow fever,⁶ SARS-CoV-2,⁷ COVID-19 vaccination,^8,9 streptococcal pharyngitis,¹⁰, and West Nile virus.¹¹

Here we present a case of an otherwise healthy male presenting with both bilateral and recurrent AIM, features that have been described independently. A literature review in February 2024 utilizing PubMed and Google Scholar using the key words “acute idiopathic maculopathy”, “bilateral”, and “recurrent” did not return any results of cases where a single patient met both criteria of bilateral and recurrent disease.

2. Case report

A 35-year-old healthy male presented with two weeks of blurred vision, progressive paracentral scotomata, and photopsias in the right eye. On exam, visual acuity was 20/20 OU, with no relative afferent pupillary defect, and slit lamp exam was unremarkable. Fundoscopic examination revealed mild temporal peripapillary retinal thickening and whitening extending to the fovea OD; OS was unremarkable (Fig. 1). Multimodal diagnostic imaging was performed. Fundus autofluorscence (FAF) showed hyperautofluorescence in the area of retinal whitening (Fig. 2). Fluorescein angiography (FA) revealed early hypofluorescence and late frames of hyperfluorescence, consistent with pooling subfoveally and staining in the nasal macular distribution previously noted (Fig. 3). The same area on indocyanine green angiography (ICG) showed hypocyanescence in all frames; OCT-Angiography (OCT-A) demonstrated choriocapillaris flow deficit in the area of hypocyanescence (Fig. 4). Ocular coherence tomography (OCT) demonstrated presence of intraretinal fluid at the level of the inner segments of the photoreceptors consistent with a bacillary layer detachment (BALAD),¹, minimal subretinal fluid, and a thick choroid OD (Fig. 5). B-scan ultrasound noted mild thickening of the macula.

Fig. 1.

OCT OD with a bacillary layer detachment (white arrowhead), minimal subretinal fluid (arrow), shaggy appearance of photoreceptors in the nasal macula (green arrowheads), and a thickened choroid. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2.

Fundus photography at initial presentation. OD (left) shows deep retina whitening and thickening of the nasal macula; OS (right) is normal.

Fig. 3.

FAF OD (left) with temporal peripapillary hyperautofluorescence; OS (right) is normal.

Fig. 4.

Early FA OD (left) with hypofluorescence in the nasal macula. Late frame (right) demonstrating staining in nasal macula with pooling within the foveal bacillary layer detachment.

Fig. 5.

ICG angiography OD with hypocyanescence in both early (left) and late (middle) frames. 6mm En face OCT-A segmented to the choriocapillaris (right) with reduced flow signal in nasal macula, corresponding to the same area as noted on ICG.

One week later, follow-up examination revealed worsening central visual acuity (20/60 uncorrected), with increased subretinal fluid and perifoveal hyperautofluorescence. Workup included unremarkable complete blood count and chest radiograph, and negative Quantiferon and Rapid Plama Reagin (RPR) and fluorescent treponemal antigen absorption test (FTA) serum testing. Coxsackie immunoglobulin titers were not obtained. Given further involvement of the fovea and worsening central vision, the decision was made to start oral prednisone 60mg for the patient's placoid-like white dot appearance.

Two weeks after initiation of prednisone, the patient's exam improved, including improved visual acuity (20/40-1) and reduced retinal whitening. OCT showed resolution of subretinal fluid. A slow prednisone taper was undertaken. At the 2-month follow-up visit (one week off prednisone), visual acuity was 20/25 + 2 OD with nearly resolved retinal whitening and corresponding normalization of autofluorescence. OCT further demonstrated reconstitution of the ellipsoid zone. Similar findings were noted at the 4 month follow up appointment (Fig. 6). The imaging findings remained resolved for seven months after the initial episode in the right eye.

Fig. 6.

Right eye imaging four months after initial presentation, off steroids. Multimodal imaging demonstrated resolution of pathology.

Nine months after initial presentation of OD symptoms, the patient returned with complaints of decreased visual acuity in his left eye. On exam, visual acuity was 20/25 + 2 OD and 20/20 OS. There was no relative afferent pupillary defect and slit lamp exam was unremarkable. Fundoscopic examination revealed mild whitening in the nasal macula near the nerve OS. OCT showed loss of the ellipsoid layer and disruption of the interdigitation zone OS, with RPE loss in the nasal macula, and a thickened choroid (Fig. 7). Combined FA/ICG OS showed a new area of hyperfluorescence consistent late staining perifoveally extending to the nasal macula (Fig. 9) with hypocyanescence in the same distribution (Fig. 10). Choriocapillaris flow deficit in the choriocapillaris on OCT-A corroborated the ICG findings (Fig. 11). For the asymptomatic right eye, imaging remained stable without recurrence of the disease (Fig. 8).

Fig. 7.

Left eye imaging at initial symptom onset. Color fundus photo (top left) with thickening and whitening of the nasal macula. FAF (top right) with hyperautofluorescence. Corresponding central OCT (bottom) shows a band-like hyperreflectivity of outer retinal layers (red arrowhead) in addition to the disruption of the outer segments (green arrowhead). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 9.

FA OS with early hypofluorescence (left) and late frames with staining (right) in the nasal macula.

Fig. 10.

Early (left) and late (middle) frame ICG OS with hypocyanescence. 6mm en face OCT-A segmented to the choriocapillaris (right) with corresponding reduced flow signal.

Fig. 11.

Multimodal imaging of the left eye one month after symptom onset. Color fundus photo (top left) with resolution of retinal whitening. FAF (top right) with minimal hyperautofluorescence. OCT (bottom left) with improving outer segments morphology (green arrowheads). 6mm en face OCT-A of the choriocapillaris (bottom right) with improved flow signal in the nasal macula. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 8.

Multimodal imaging of the right eye at the presentation of symptom onset of the left eye. Color fundus photo (top left), FAF (top right), OCT (bottom left), and FA late frame (bottom right) without change from last visit. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

At this stage, changes in the nasal macula OS appeared consistent with the initial OD changes. A differential of Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) versus Ampiginous Choroiditis (Relentless Placoid Choriorentitis) were considered and the patient was restarted on oral prednisone 60mg. Since a recent complete work-up had been done, a repeat work-up was not considered at this time.

A week later, follow up revealed improved autofluorescence with stable visual acuity. Steroid taper was started. 1 month after initial presentation of OS symptoms, whitening resolved on fundoscopic examination and OCTA demonstrated reconstitution of the choriocapillaris to normal; this was corroborated by ICG findings. Steroid taper was continued with maintained visual acuity and improvement of subjective distortion OS over a total of 6 weeks.

More than three years after the patient's initial OD presentation, he returned with complaints of OD visual disturbance with central distortion. On exam, VA was 20/40 OD, 20/20 OS. Fundoscopic examination and multimodal imaging revealed findings similar to three years prior: nasal and central whitening OD with a small serous detachment. OCT showed recurrent but more extensive BALAD, now involving the fovea (Fig. 12). FA demonstrated similar hyperfluorescence; ICG demonstrated hypocyanescence with a larger area than the first episode. Given involvement of the fovea, patient's worse presentation, and quick resolution when previously treated with oral steroids, he was started on prednisone 60mg daily.

Fig. 12.

Right eye imaging at symptom onset of recurrent episode. OCT (left) with recurrent bacillary layer detachment (white arrowhead). The nasal outer segments are elongated (green arrowheads). The choroid is thick. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

One week after taking prednisone, the patient returned with stable visual acuity of 20/40 + 1 OD. OCT demonstrated significant improvement with near resolution of the subretinal fluid, with patchy outer retinal attenuation nasally OD. Thus, a prednisone taper was initiated.

One month after initial presentation, VA improved to 20/15 OU with improvement of imaging findings. Steroid taper was continued and at 2 month follow up, VA was stable, with evidence of continued outer retinal reconstitution on OCT (Fig. 13).

Fig. 13.

OCT OD with reconstitution of the ellipsoid zone, which remains slightly attenuated (green arrowheads) approximately six weeks after symptom onset. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

3. Discussion

AIM is a rare cause of acute, typically unilateral, vision loss in otherwise healthy, young patients. Since its original description by Yannuzzi and colleagues in 1991, several case reports and series have helped to define the typical clinical characteristics of the disease. At the time of presentation, most patients show irregular areas of gray-white retinal macular discoloration with associated sub-retinal thickening at the level of the RPE and exudative retinal detachment, which can occur with or without foveal involvement.^1,2,12 Ocular coherence tomography (OCT) in patients confirmed subfoveal retinal detachment and photoreceptor IS/OS junction disruption, which in some instances were reversible and associated with improvement in visual acuity.^12,13. ICG angiography has previously demonstrated abnormalities in choroidal vasculature, suggesting active choroidal inflammation in the etiology of AIM.¹²

Differential diagnosis considerations include choroidal neovascularization, central serous chorioretinopathy, Vogt-Koyanagi-Harada disease, syphilitic retinitis, ampiginous choroidopathy, serpiginous choroidopathy, and APMPPE.^1,13

This patient initially presented with unilateral disease without a viral prodrome, however, it became bilateral within one year, and ultimately consisted of three distinct episodes between both eyes over the course of three years. Previous case reports on AIM have demonstrated same-site recurrence (within 1 year) or contralateral recurrence in the initially unaffected eye (after 3 years).^3,4

The FA and ICG findings of early hypofluorescence and later hyperfluorescence with hypocyanescence seen in the patient are well described in other reports of AIM.^14,15 The OCT-A findings demonstrating choriocapillaris flow deficit in the same distribution of the ICG hypocyanescence have also previously been reported.¹¹ Interestingly, APMPPE, serpiginous choroidopathy, and ampiginous choroiditis all share the OCT, FA, ICG, and OCT-A findings as listed above. The description of bacillary layer detachment can be seen in numerous posterior segment inflammatory diseases, including those on the APMPPE spectrum and AIM.¹⁶

With the advantage of 3-year long-term follow up involving multimodal imaging of FA, ICG, OCT, OCTA, and autofluorescence, we were able to correlate imaging findings, as well as capture two episodes of recurrence. In the first and second presentations, the ellipsoid zone was reconstituted within two months and one month in the right eye and left eye, respectively, with putative response to oral steroids. While we cannot appoint a causal relationship, the timing of treatment and resolution seems to suggest a strong response to steroid therapy. The relatively short timeframe between episodes (seven months) and the lack of viral prodrome would not be consistent with typical coxsackie infections. The third presentation, which occurred after a 2-year gap of no visual complaints, appeared to be a recurrence of AIM in the right eye. Recurrence of both AIM and APMPPE is rare but typically has been reported with worse prognosis.^4,17 RPE damage indeed increased in size during recurrence of the right eye, consistent with prior reports, however, the repeated recurrence beyond six months is more characteristic of relentless placoid chorioretinitis. Yet, the fairly limited involvement and interval resolution between each presentation is unlike classic relentless placoid.¹⁸

This case study, which shows both bilateral and recurrent episodes within the same patient, provides support for AIM being on a clinical spectrum of APMPPE and serpiginous choroiditis.

Indeed, it has been hypothesized that APMPPE and serpiginous choroiditis may represent a disease spectrum, as opposed to discrete diseases, hence the term “ampiginous” for relentless placoid chorioretinitis. It is theorized that AIM may be on the spectrum, given their similar clinical presentations, clinical course, and exam findings consistent with disruption of choriocapillaris blood flow. ICG angiography findings in this case study are consistent with choroidal ischemia localizing with the area of bacillary detachment, which has been described previously using OCTA imaging,¹⁶ but not using ICG to our knowledge. While AIM is reported to improve spontaneously and generally no treatment is recommended, this case reports highlights rapid improvement in three episodes when taking oral steroids. The single report of recurrent AIM noted decreased visual acuity after the third episode,⁴, yet this report is suggestive that early diagnosis and treatment may help to spare vision, which is consistent with other inflammatory conditions, such as those on the APMPPE spectrum.

4. Conclusion

Acute idiopathic maculopathy has characteristic findings on multimodal imaging that mimic the diseases on the APMPPE spectrum. This case highlights that prompt treatment with oral steroids yields excellent visual acuity results in the setting of recurrent disease.

CRediT authorship contribution statement

Yichen Fan: Writing – original draft, Data curation. Zachary A. Kroeger: Writing – review & editing, Writing – original draft, Formal analysis, Data curation. Christina J. Flaxel: Writing – review & editing, Supervision, Conceptualization.

Patient consult

Consent to publish the case report was not obtained. This report does not contain any personal information that could lead to the identification of the patient.

Authorship

All authors attest that they meet the current ICMJE criteria for Authorship.

Claims of priority

After conducting a literature review in February 12, 2024 utilizing PubMed and Google Scholar using the key words “acute idiopathic maculopathy”, “bilateral”, and “recurrent” we did not find any prior reports of a single patient with both recurrent and bilateral acute idiopathic maculopathy.

Proprietary interests

None.

Funding

Unrestricted grant from Research to Prevent Blindness to Casey Eye Institute EY01010572.

Financial support

None.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.