Acute Posterior Multifocal Placoid Pigment Epitheliopathy
|Acute Posterior Multifocal Placoid Pigment Epitheliopathy|
|Classification and external resources|
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an inflammatory chorioretinopathy which was first described by Gass in 1968. It is classified as a White Dot Syndrome. APMPPE is usually bilateral, affects women and men equally, has a tendency to occur between the 2nd to 4th decades, and can have associated systemic conditions. The most common complaint is blurred vision with central or paracentral scotomas. Cases are often self-limited and visual symptoms resolve by 4 to 8 weeks. There is no consensus on treatment, however steroids have been attempted to hasten visual recovery especially in cases with macular involvement.
In 1968, Gass first described acute posterior multifocal placoid pigment epithelium (APMPPE) by presenting the clinical and flouroscein angiography findings in three young females with bilateral central vision loss.
The exact etiology of APMPPE is unknown, however some believe that it is secondary to a delayed-type hypersensitivity-induced occlusive vasculitis. Its suggested immune driven nature is due to its association with HLA-B7 and HLA-DR2 genetic haplotypes.
Approximately 33% of patients report a preceding viral or flu-like illness prior to APMPPE symptom onset. APMPPE has been described in cases of thyroiditis, erythema nodosum, granulomatosis with polyangiitis, polyarteritis nodosa, nephritis, sarcoidosis, scleritis, ulcerative colitis, central nervous system (CNS) vasculitis, and post-vaccination. Other infectious associations include group A streptococcus, adenovirus-5, influenza, hepatitis B, Lyme disease, mumps, and tuberculosis. Genetics may play a role in an individual’s risk for APMPPE as several associations have been reported including HLA-B7 and HLA-DR2 genetic haplotypes. Recurrence is rare, but typically has been reported with worse prognosis.
The exact pathogenesis is controversial but is believed to be due to inflammation at the level of the choriocapillaris resulting in hypoperfusion and ischemia of the RPE and photoreceptors. In later stages, the inflamed choroid and retina manifests with RPE atrophy and hyperpigmentation.
There are no recognized preventative measures.
Diagnosis is made via clinical presentation and fundoscopic examination. Fluorescein angiography is helpful in confirming the diagnosis.
Patients typically notice a rapid onset of blurred vision associated with central and paracentral scotomas. Photopsias have been reported prior to vision loss. Symptoms are usually bilateral, asymmetric and can occur several days apart. Visual acuity can range from 20/40 to count-fingers depending on the extent of foveal involvement. Headache and other neurological symptoms may be noted and may appear months after the ocular involvement.
Anterior segment exam is usually normal, though anterior uveitis can be present. There may be mild vitritis present in 50% of cases. Fundoscopic examination typically shows multiple bilateral yellow-white placoid lesions at the level of RPE and choroid 1-2 disc diameters throughout the fundus, posterior to the equator. The lesions gradually fade over the course of 1-2 weeks. New lesions may appear in the periphery up to 3 weeks following onset (radially or linearly). Papillitis may occur, but cystoid macular edema is uncommon.
Older lesions are replaced with RPE atrophy or hyperpigmentation. There are reports of associated retinal vasculitis, vein occlusion, subhyaloid hemorrhage, retinal neovascularization, exudative retinal detachment, and rare choroidal neovascular membrane formation.
No specific laboratory tests exist to confirm the diagnosis. Fluorescein angiography and Indocyanine Green angiography are typically performed. Optical coherence tomography and fundus autoflourescense may also have a role in diagnoses. Characteristic findings of these diagnostic procedures include:
- Fluorescein Angiogram (FA): Early hypofluorescence (blockage) corresponding to the placoid lesions followed by late, irregular hyperfluorecent staining.
- Indocyanine Green (ICG) Angiogram: Early and late hypofluorescence corresponding to the placoid lesions.
- Fundus autoflourescense (FAF): Early and late hypoautoflourescence corresponding to the placoid lesions. Hypoautoflourescence may persist at borders after lesion resolution.
- Optical coherence tomography (OCT): Hyperreflectivity from the outer plexiform layer to the RPE with normal retinal thickness in acute lesions. Hyperreflectivity of outer layers resolve along with resolution of the lesion.
Other White-Dot syndromes can resemble APMPPE. These include, but are not limited to:
- Multiple evanescent white dot syndrome- unilateral, smaller lesions, disc edema present, foveal granularity
- Serpiginous choroiditis (especially in chronic, recurrent cases)- important differential and tuberuculosis needs to be ruled out.
- Relentless placoid choroiditis
- Multifocal choroiditis and panuveitis
- Punctate inner choroidopathy
- Birdshot chorioretinopathy
- Vogt Koyanagi Harada syndrome- The APMPPE and VKH may lie in a spectrum of disease, and atypical APMPPE may present unilaterally with subretinal fluid, papillitis, retinal vasculitis which respond well to systemic steroid.
Other infectious uveitis (tuberculosis, fungal disease, syphilis), choroidal metastases, and lymphoma may present with placoid lesions as well and should be ruled out with appropriate tests if clinical suspicion high.
Prognosis and General Management
APMPEE is self-limiting with a generally good prognosis with the majority of affected patients achieving a visual acuity of 20/40 or better. However, an aggressive variant (relentless placoid choroioretintis/ampiginous choroiditis) has also been described which has characterestics of both APMPPE and serpiginous choroiditis, It has high recurrence rate, longer period of disease activity, and numerous multifocal lesions (>50) scattered throughout the fundus. The relapses of this disease may be controlled with immunomodulatory therapy.
Visual recovery typically takes 4 weeks, but can extend to 6 months in some patients. A recent review by Fiore T el al. analyzed 183 articles related to APMPPE and concluded that 25% of patients had a visual acuity of 20/50 or worse. Foveal involvement confers a worse visual prognosis. There is no current consensus on treatment although steroids have been utilized and reported to be beneficial in cases of foveal involvement and associated CNS vasculitis. Future studies are needed to evaluate dosage, duration, and effects of steroid treatment. All patients with a new diagnosis of APMPPE should receive a full neurologic and systemic work-up to evaluate for CNS vasculitis and other associated systemic conditions.
- American Academy of Ophthalmology. Uveitis: Acute posterior multifocal placoid pigment epitheliopathy Practicing Ophthalmologists Learning System, 2017 - 2019 San Francisco: American Academy of Ophthalmology, 2017.
Burés-Jelstrup A, Adán A, Casaroli-Marano R. Acute posterior multifocal placoid pigment epitheliopathy. A study of 16 cases. Arch Soc Esp Oftalmol. 2007 May;82(5):291-7
Hsu CT, Harlan JB, Goldberg MF, Dunn JP. Acute posterior multifocal placoid pigment epitheliopathy associated with a systemic necrotizing vasculitis. Retina. 2003 Feb;23(1):64-8.
Quillen DA et al. The white dot syndromes. Am J Ophthalmol. 2004 Mar;137(3):538-50
Comu S, Verstraeten T, Rinkoff JS, Busis NA. Neurological manifestation of acute posterior multifocal placoid pigment epitheliopathy. Stroke. 1996 May;27(5):996-1001
O’Halloran HS et al. Acute multifocal placoid pigment epitheliopathy and central nervous system involvement: nine new cases and a review of the literature. Ophthalmology. 2001 May;108(5):861-8
Fiore T el al. Acute posterior multifocal placoid pigment epitheliopathy: outcome and visual prognosis. Retina. 2009 Jul-Aug;29(7):994-1001
Retina and Vitreous, Section 12. Basic and Clinical Science Course, AAO, 2009-10.
Gass JD. Acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol. 1968 Aug;80(2):177-85
Jones NP. Acute posterior multifocal placoid pigment epithliopathy. Br J Ophthalmol. 1995 Apr;79(4):384-9
Steiner S, Goldstein D. Imaging in the Diagnosis and Management of APMPPE. International Ophthalmology Clinics. 2012;52(4):211-219.
Mirza G, Jampol L. Acute posterior multifocal placoid pigment epitheliopathy. In Ryan SJ. Retina, 5th Edition. Elsevier, 2013: 1341-1346.
- Vedantham V, Ramasamy K. Atypical manifestations of acute posterior multifocal placoid pigment epitheliopathy. Indian J Ophthalmol. 2006 Mar;54(1):49-52. PubMed PMID: 16531674.