Acute posterior multifocal placoid pigment epitheliopathy presenting with granulomatous panuveitis

Abstract

Purpose

To describe a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) presenting with granulomatous panuveitis and to highlight multimodal ocular imaging findings useful for diagnosis.

Observations

A 20-year-old Japanese man presented with acute vision loss in the left eye. Best-corrected visual acuity was 20/20 in the right eye and 20/250 in the left eye. Slit-lamp examination revealed bilateral mutton-fat keratic precipitates with anterior chamber cells and anterior vitreous cells. Fundus examination showed multiple confluent yellowish-white placoid lesions bilaterally. Angiographic and OCT findings were characteristic of APMPPE. These included the angiographic reversal phenomenon on fluorescein angiography, persistent hypofluorescence on indocyanine green angiography, and the angular sign of Henle fiber layer hyperreflectivity on optical coherence tomography. Systemic evaluation, including syphilis serology, an interferon-gamma release assay for tuberculosis, serum angiotensin-converting enzyme and soluble interleukin-2 receptor levels, viral serology, and chest radiography, did not identify an associated infectious or inflammatory disease. Bilateral sub-Tenon triamcinolone acetonide injections, oral prednisolone, and topical corticosteroids led to rapid resolution of inflammation and recovery of visual acuity. The patient remained free of recurrence for 13 months after presentation, including more than seven months after cessation of therapy.

Conclusions and importance

APMPPE should remain in the differential diagnosis of granulomatous panuveitis when placoid fundus lesions are present. Careful ocular imaging and systemic evaluation are useful for distinguishing APMPPE from VKH disease, sarcoidosis, and infectious uveitis.

1. Introduction

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an inflammatory chorioretinopathy characterized by the acute onset of bilateral yellowish-white placoid lesions.¹ It typically affects otherwise healthy young adults and is often preceded by a viral prodrome. The condition has been reported in association with infectious diseases, including tuberculosis² and Lyme disease,³ and with systemic inflammatory disorders, such as sarcoidosis⁴ and granulomatosis with polyangiitis.⁵ Rare cases have been reported after vaccination.⁶ These observations suggest that immune-mediated mechanisms may contribute to its pathogenesis.

Angiographic and optical coherence tomography (OCT) findings provide important clues to choriocapillaris involvement and associated outer retinal changes.^6,7 Fluorescein angiography (FA) typically shows early hypofluorescence followed by late staining, the so-called “reversal phenomenon,” while OCT may demonstrate acute-phase changes such as transient choroidal thickening and outer retinal disruption.6, 7, 8.

The diagnosis can become challenging when granulomatous anterior segment inflammation is present. Mutton-fat keratic precipitates (KPs) are uncommon in APMPPE and may instead suggest Vogt–Koyanagi–Harada (VKH) disease, sarcoidosis, or other granulomatous uveitic entities. We report a case of APMPPE presenting with bilateral granulomatous panuveitis. Angiographic and OCT features helped establish the diagnosis despite atypical anterior segment findings.

2. Case presentation

A 20-year-old Japanese man presented with sudden painless vision loss in the left eye for several days. He had no recent febrile illness, vaccination, or systemic disease. Best-corrected visual acuity (BCVA) was 20/20 in the right eye and 20/250 in the left eye. Intraocular pressure was 11 mmHg in both eyes. Slit-lamp examination disclosed bilateral mutton-fat KPs (Fig. 1a), 1+ anterior chamber cells, and 1+ anterior vitreous cells. Fundus examination showed multiple ill-defined yellowish-white placoid lesions in both eyes (Fig. 1b). The lesions extended from the posterior pole to the midperiphery, showed partial confluence, and were more numerous than in typical APMPPE. There was no optic disc edema or retinal vasculitis.

Fig. 1.

Anterior and posterior segment findings at initial presentation.

(a) Anterior segment photograph of the left eye showing mutton-fat keratic precipitates.

(b) Ultrawide-field color scanning laser ophthalmoscopy (SLO) images (Mirante, Nidek Co., Ltd., Gamagori, Japan) of the right (left panel) and left (right panel) eyes, demonstrating multiple, ill-defined, yellowish-white placoid lesions with partial confluence extending from the posterior pole to the midperiphery.

(c, d) Vertical spectral-domain optical coherence tomography (SD-OCT) scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany) of the left (c) and right (d) eyes. Both eyes show diffuse choroidal thickening and hyperreflective disruption of the outer retinal layers, extending from the outer plexiform layer to the retinal pigment epithelium (RPE). Although the interocular difference is subtle, hyperreflective disruption of the outer retinal layers involves the foveola in the symptomatic left eye, whereas the foveolar outer retinal architecture is relatively preserved in the asymptomatic right eye. Scattered hyporeflective areas are observed within the choriocapillaris layer (arrow), where normal vascular structures are indistinct, indicating patchy hypoperfusion. In the macular region, the characteristic angular sign of Henle fiber layer hyperreflectivity (ASHH) is also observed (arrowheads); in the right eye, the ASHH is located slightly eccentric to the foveola.

(e, f) Fundus autofluorescence (FAF) images (Spectralis, Heidelberg Engineering, Heidelberg, Germany) of the left (e) and right (f) eyes showing central hypoautofluorescence with surrounding hyperautofluorescent margins in the placoid lesions. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

OCT revealed diffuse choroidal thickening in both eyes, with subfoveal choroidal thickness (SFCT) of 552 μm in the left eye and 550 μm in the right eye (Fig. 1c and d, respectively). Scattered hyporeflective areas were observed within the superficial choroidal layer corresponding to the choriocapillaris, where normal vascular structures were indistinct, indicating patchy hypoperfusion. Corresponding to the placoid lesions, hyperreflectivity and disruption of the outer retinal layers extended from the outer plexiform layer to the retinal pigment epithelium. Although these findings were present bilaterally and the interocular difference was subtle, the degree of foveolar outer retinal involvement differed between the eyes. In the symptomatic left eye, outer retinal disruption involved the foveola, whereas the foveolar outer retinal architecture was relatively preserved in the asymptomatic right eye. In the macular region, the angular sign of Henle fiber layer hyperreflectivity (ASHH) was also observed; in the right eye, this finding was located slightly eccentric to the foveola.

Fundus autofluorescence (FAF) showed bilateral placoid lesions with central hypoautofluorescence and hyperautofluorescent margins, without marked interocular asymmetry (Fig. 1e and f). FA demonstrated the classic reversal phenomenon, with early hypofluorescence (Fig. 2a) followed by late hyperfluorescence (Fig. 2b). There was no multifocal pinpoint leakage, optic disc staining, or vascular leakage suggestive of VKH disease. Indocyanine green angiography (ICGA) revealed multiple areas of persistent hypofluorescence from the early to late phases, indicating widespread choriocapillaris hypoperfusion (Fig. 2c and d).

Fig. 2.

Angiographic findings of the right eye at initial presentation.

(a) Early-phase fluorescein angiography (FA) demonstrating multiple hypofluorescent areas corresponding to the placoid lesions.

(b) Late-phase FA showing the characteristic “reversal phenomenon,” with progressive late hyperfluorescence (staining) of the lesions.

(c) Early-phase indocyanine green angiography (ICGA) revealing widespread hypofluorescent areas corresponding to the placoid lesions.

(d) Late-phase ICGA confirming persistent hypofluorescence of the lesions, indicating sustained choriocapillaris hypoperfusion.

The patient had no extraocular symptoms. Systemic evaluation did not identify findings suggestive of an associated infectious or inflammatory disorder. C-reactive protein, angiotensin-converting enzyme, and soluble interleukin-2 receptor levels were unremarkable. Rapid plasma reagin and Treponema pallidum antibody tests were negative, as was an interferon-gamma release assay for tuberculosis. Serologic testing showed no evidence of acute varicella-zoster virus, herpes simplex virus, or cytomegalovirus infection. A mild microcytic hypochromic anemia was noted, but other blood cell counts and renal and hepatic function tests were normal. Chest radiography performed before initiation of systemic corticosteroid therapy showed no significant abnormalities. Chest computed tomography was not performed because the clinical, laboratory, and chest radiographic findings did not strongly suggest sarcoidosis.

Despite the atypical granulomatous panuveitis, the characteristic angiographic and OCT findings supported a diagnosis of APMPPE. Corticosteroid therapy was selected because of foveal involvement, marked vision loss in the left eye, and clinically evident panuveitis. A sub-Tenon injection of triamcinolone acetonide (40 mg) was administered first to the left eye, followed three days later by injection into the right eye. Oral prednisolone 30 mg/day (approximately 0.5 mg/kg/day) was initiated, and topical betamethasone 0.1% six times daily was started in both eyes. Inflammation resolved rapidly, BCVA in the left eye improved to 20/20 within three weeks, and the placoid lesions gradually regressed. Topical corticosteroids were tapered and discontinued by day 51, and oral prednisolone was tapered off over 170 days.

At 13 months after presentation, including more than seven months after cessation of therapy, the patient remained asymptomatic with BCVA of 20/20 in both eyes and no recurrence. No extraocular manifestations suggestive of sarcoidosis, VKH disease, or other systemic inflammatory disorders developed. Fundus examination showed only a few faint residual whitish lesions (Fig. 3a). OCT confirmed resolution of choroidal thickening, with subfoveal choroidal thickness reduced to 422 μm in the left eye and 427 μm in the right eye, although slight irregularity of the interdigitation zone (IZ) persisted in areas corresponding to resolved lesions (Fig. 3b).

Fig. 3.

Post-treatment follow-up imaging 13 months after initial presentation.

(a) Ultrawide-field color scanning laser ophthalmoscopy (SLO) images (Mirante, Nidek Co., Ltd., Gamagori, Japan) of the right (left panel) and left (right panel) eyes, demonstrating resolution of the acute placoid lesions with only a few faint residual whitish spots.

(b) Vertical spectral-domain optical coherence tomography (SD-OCT) scan (Spectralis, Heidelberg Engineering, Heidelberg, Germany) of the left eye demonstrating normalization of choroidal thickness. The outer retinal architecture is largely restored, although slight irregularity of the interdigitation zone (IZ) persists in areas corresponding to the resolved lesions (arrowheads). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

3. Discussion

This case shows that APMPPE may present with granulomatous panuveitis and mutton-fat KPs, which are unusual for this disorder. Despite these atypical anterior segment findings, the placoid lesions and characteristic angiographic and OCT features supported the diagnosis. The subsequent monophasic course without recurrence was also consistent with APMPPE.

Another important feature of this case was the clinically asymptomatic but affected right eye. Although the patient reported symptoms only in the left eye, the right eye showed placoid lesions, choroidal thickening, and choriocapillaris-level abnormalities on imaging, indicating subclinical fellow-eye involvement. Comparative OCT provided a plausible anatomical correlate for the inter-eye difference in symptoms, although the interocular difference was subtle: in the symptomatic left eye, outer retinal disruption involved the foveola, whereas the foveolar outer retinal architecture was relatively preserved in the asymptomatic right eye, with the angular sign of Henle fiber layer hyperreflectivity located slightly eccentric to the foveola. This observation does not establish a predictive imaging marker, but it emphasizes that careful assessment of the asymptomatic fellow eye may be clinically informative in APMPPE.

Only a few cases of APMPPE with granulomatous uveitis have been reported (Table 1).^5,9, 10, 11 In these cases, granulomatous inflammation was present either at the initial presentation, as in the present case, or developed after the appearance of placoid lesions. This temporal variability is clinically relevant. Granulomatous anterior segment findings at presentation may lead clinicians to prioritize VKH disease, sarcoidosis, or other granulomatous uveitic entities over APMPPE. Unlike earlier reports that predated the widespread use of OCT, the present case documents this atypical presentation using contemporary ocular imaging, including OCT, FA, ICGA, and FAF. Two previously reported cases were associated with a systemic inflammatory condition or trigger, namely granulomatosis with polyangiitis and influenza vaccination.^5,11 Even when angiographic and OCT features are characteristic of APMPPE, a thorough systemic workup remains warranted when granulomatous inflammation is present.

Table 1.

Clinical and imaging features relevant to diagnosis in reported cases of APMPPE with granulomatous uveitis.

	Alvi & Fishman (1995)9	Chiquet et al. (1999)5	Alpay et al. (2012)10	Gonome et al. (2016)11	Present Case
Age/Sex	30/Male	43/Male	43/Male	30s/Female	20/Male
Granulomatous Anterior Segment Signs	Mutton-fat KPs, Koeppe nodules	Mutton-fat KPs	Mutton-fat KPs	Iris and angle nodules	Mutton-fat KPs
Timing of Granulomatous Inflammation	At initial presentation	At initial presentation	4 days after placoid lesions	1 month after placoid lesions	At initial presentation
Systemic Association or Trigger	None reported	GPA	None reported	Influenza vaccination; flu-like symptoms ∼10 days before ocular onset	None identified
OCT Findings Relevant to Diagnosis	Not available (pre-OCT era)	Not available (pre-OCT era)	Not reported	RPE swelling	Outer retinal disruption; ASHH; acute-phase choroidal thickening; hyporeflective areas in the superficial choroid
Angiographic Findings Relevant to Diagnosis	FA reversal phenomenon; mild bilateral optic disc leakage	FA reversal phenomenon; ICGA hypofluorescent lesions	FA reversal phenomenon	FA reversal phenomenon; ICGA hypofluorescent lesions; left optic disc leakage	FA reversal phenomenon; persistent ICGA hypofluorescence; no optic disc staining, vascular leakage, or multifocal pinpoint leakage
Posterior Segment Inflammatory Findings	1+ vitreous cells; bilateral placoid lesions	Mild vitreous haze; bilateral placoid subretinal lesions	3+ vitreous cells; bilateral placoid lesions	Anterior vitreous cells; bilateral placoid lesions; left macular edema; left optic disc edema	1+ anterior vitreous cells; bilateral placoid lesions; no optic disc edema or retinal vasculitis

APMPPE: acute posterior multifocal placoid pigment epitheliopathy; KPs: keratic precipitates; GPA: granulomatosis with polyangiitis; OCT: optical coherence tomography; RPE: retinal pigment epithelium; ASHH: angular sign of Henle fiber layer hyperreflectivity; FA: fluorescein angiography; ICGA: indocyanine green angiography.

The main diagnostic challenge is distinguishing APMPPE from other granulomatous uveitic entities, particularly VKH disease and sarcoidosis. Among these entities, VKH disease warrants detailed imaging-based comparison because it can share bilateral choroidal inflammation and transient choroidal thickening with acute APMPPE. Recent imaging studies have also emphasized that transient choroidal thickening is not specific to VKH disease and may be seen in acute APMPPE.^7,8,12,13 However, the angiographic and OCT patterns differ between the two entities.

In VKH disease, FA typically shows multiple punctate areas of subretinal leakage, pooling of subretinal dye, and optic disc staining or leakage.^14,15 OCT commonly demonstrates serous retinal detachment, marked choroidal thickening, and diffuse obscuration of the choroidal vascular architecture, reflecting stromal choroidal inflammation.^15,16 ICGA may show numerous hypofluorescent dark dots corresponding to stromal choroidal lesions.^15,17 By contrast, APMPPE is characterized by placoid lesions with the FA reversal phenomenon, persistent ICGA hypofluorescence corresponding to choriocapillaris hypoperfusion, and outer retinal OCT abnormalities, including the angular sign of Henle fiber layer hyperreflectivity and outer retinal disruption.6, 7, 8^,18 In the present case, the FA reversal phenomenon, persistent ICGA hypofluorescence, and outer retinal OCT abnormalities, including the angular sign of Henle fiber layer hyperreflectivity, supported the diagnosis of APMPPE. The superficial choroidal hyporeflective areas corresponding to persistent ICGA hypofluorescence further supported choriocapillaris-level involvement. In contrast, the absence of VKH-typical findings, including multifocal pinpoint leakage, subretinal dye pooling, optic disc staining or leakage, and serous retinal detachment, made VKH disease less likely.

The mechanism linking APMPPE and granulomatous anterior inflammation remains uncertain. APMPPE is thought to involve a T-cell-mediated delayed hypersensitivity reaction,⁶ and histopathological reports of severe APMPPE complicated by cerebral vasculitis have shown granulomatous inflammation involving the meninges and choroid.^19,20 Granulomatous panuveitis may therefore represent an uncommon expression of the same inflammatory process.

This case serves as a diagnostic reminder that APMPPE should remain in the differential diagnosis of granulomatous panuveitis with mutton-fat KPs when placoid fundus lesions are present. Careful ocular imaging and systemic evaluation can help distinguish APMPPE from VKH disease, sarcoidosis, and infectious uveitis.

Authorship

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

Patient consent

Written informed consent was obtained from the patient for publication of this case report and the accompanying clinical images.

Ethics statement

This study was approved by the Institutional Review Board of Yokohama City University Hospital (Approval No. 2025-071) and was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Declaration of generative AI and AI-assisted technologies in the manuscript preparation process

The authors declare that no generative AI or AI-assisted technologies were used in the preparation of this manuscript.

Funding

No funding or grant support.

CRediT authorship contribution statement

Shun Kanasashi: Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Validation, Visualization, Writing – original draft. Jutaro Nakamura: Conceptualization, Investigation, Methodology, Resources, Supervision, Validation, Writing – review & editing. Nobuhisa Mizuki: Conceptualization, Investigation, Methodology, Resources, Supervision, Validation, Writing – review & editing.

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.