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Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)

Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)

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First described by Gass in 1968, acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an acquired inflammatory disorder affecting the retina, retinal pigment epithelium, and choroid of otherwise young healthy adults. [1] The disease is self-limited and is characterized by multiple yellow-white placoid subretinal lesions of the posterior pole, as shown below. The lesions are frequently bilateral and in various stages of evolution, typically resolving in weeks to months and leaving circumscribed areas of retinal pigment epithelial disturbance.

Visual acuity may be affected significantly if the macula is involved, but recovery is the rule with or without systemic therapy, with 80% of those eyes affected achieving a visual acuity of 20/40 or better. The cause is unknown but believed to be a hypersensitivity-induced vasculitis involving not only terminal choroidal lobules but also diffuse systemic large and small vessels.

The pathophysiology of APMPPE is somewhat speculative.

Two major theories concerning the pathogenesis of APMPPE have been proposed based on clinical and diagnostic findings. No histopathological evidence is available on acute or subacute stages of the disease.

The first suggests that inflammation of the retinal pigment epithelium (RPE) and outer retina manifests as placoid lesions during the acute phase. [1]

The second theory, which is more convincing, suggests that choroidal vasculitis leads to partial occlusion of the choriocapillaris in these eyes. In turn, disruption of choroidal blood flow causes secondary ischemia of the overlying RPE and outer retina, manifesting as placoid lesions. [2]

Other findings suggestive of vasculitis include episcleritis, erythema nodosum, microvascular nephropathy, thyroiditis, optic neuritis, labyrinthitis, hearing loss, and cerebral angiitis. Meningoencephalitis occasionally has been observed.

United States

The incidence and prevalence of APMPPE is unknown. However, since the landmark description of Gass, APMPPE has been reported frequently and widely from ophthalmic centers, primarily in the United States and Western Europe. Most US patients reported in the literature reside in the northern and midwestern states.

International

Reports in the international literature have included patients from northwestern European countries, such as England, Scotland, France, Belgium, the Netherlands, and Denmark. Several reports have originated from Japan. Reports from other geographic areas have been sparse.

APMPPE usually affects healthy adults, and, other than ocular involvement, systemic manifestations are relatively uncommon. When they do occur, many systemic manifestations are usually mild and transient in nature; however, the presence of cerebral vasculitis has been associated with permanent neurologic sequelae, such as hemiparesis and even death from intracerebral edema and brain herniation in rare instances.

Almost 80% of the recorded cases include whites, with the remainder being Japanese, African American, Nepalese, and from the Indian subcontinent. Whether this racial distribution represents a predilection of APMPPE for whites or a reporting bias is unclear.

Earlier reports of APMPPE suggested a slight preponderance of women with this disease, but more recent publications suggest no sexual predilection, with equal frequency between both men and women.

The mean age of onset is approximately 27 years. The documented age range of onset is 7-66 years. The most frequent age range of occurrence of APMPPE is in those patients aged 16-40 years, representing approximately 85% of cases. About 50% of patients present in the third decade of life.

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Yeh S, Forooghian F, Wong WT, Faia LJ, Cukras C, Lew JC, et al. Fundus autofluorescence imaging of the white dot syndromes. Arch Ophthalmol. 2010 Jan. 128(1):46-56. [Medline]. [Full Text].

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Cheung CM, Yeo IY, Koh A. Photoreceptor changes in acute and resolved acute posterior multifocal placoid pigment epitheliopathy documented by spectral-domain optical coherence tomography. Arch Ophthalmol. 2010 May. 128(5):644-6. [Medline].

Goldenberg D, Habot-Wilner Z, Loewenstein A, Goldstein M. Spectral domain optical coherence tomography classification of acute posterior multifocal placoid pigment epitheliopathy. Retina. 2012 Jul. 32 (7):1403-10. [Medline]. [Full Text].

Mrejen S, Gallego-Pinazo R, Wald KJ, Freund KB. Acute posterior multifocal placoid pigment epitheliopathy as a choroidopathy: what we learned from adaptive optics imaging. JAMA Ophthalmol. 2013 Oct. 131 (10):1363-4. [Medline]. [Full Text].

Michael A. Klufas, MD , Nopasak Phasukkijwatana, MD , Nicholas A. Iafe, BA , et al. Optical Coherence Tomography Angiography Reveals Choriocapillaris Flow Reduction in Placoid Chorioretinitis. Ophthalmology Retina. January–February 2017. Volume 1, Issue 1:77–91. [Full Text].

Hirooka K, Saito W, Saito M, Hashimoto Y, Mori S, Noda K, et al. Increased choroidal blood flow velocity with regression of acute posterior multifocal placoid pigment epitheliopathy. Jpn J Ophthalmol. 2016 May. 60 (3):172-8. [Medline].

Mrejen S, Sarraf D, Chexal S, Wald K, Freund KB. Choroidal Involvement in Acute Posterior Multifocal Placoid Pigment Epitheliopathy. Ophthalmic Surg Lasers Imaging Retina. 2016 Jan. 47 (1):20-6. [Medline].

Mavrakanas N, Mendrinos E, Tabatabay C, Pournaras CJ. Intravitreal ranibizumab for choroidal neovascularization secondary to acute multifocal posterior placoid pigment epitheliopathy. Acta Ophthalmol. 2010 Mar. 88 (2):e54-5. [Medline].

Fiore T, Iaccheri B, Androudi S, Papadaki TG, Anzaar F, Brazitikos P, et al. Acute posterior multifocal placoid pigment epitheliopathy: outcome and visual prognosis. Retina. 2009 Jul-Aug. 29 (7):994-1001. [Medline].

Bugnone AN, Hartker F, Shapiro M, Pineless HS, Velez G. Acute and chronic brain infarcts on MR imaging in a 20-year-old woman with acute posterior multifocal placoid pigment epitheliopathy. AJNR Am J Neuroradiol. 2006 Jan. 27(1):67-9. [Medline]. [Full Text].

Di Crecchio L, Parodi MB, Saviano S, Ravalico G. Acute posterior multifocal placoid pigment epitheliopathy and ulcerative colitis: a possible association. Acta Ophthalmol Scand. 2001 Jun. 79(3):319-21. [Medline].

Howe LJ, Woon H, Graham EM, Fitzke F, Bhandari A, Marshall J. Choroidal hypoperfusion in acute posterior multifocal placoid pigment epitheliopathy. An indocyanine green angiography study. Ophthalmology. 1995 May. 102(5):790-8. [Medline].

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. [Medline].

Lim LL, Watzke RC, Lauer AK, Smith JR. Ocular coherence tomography in acute posterior multifocal placoid pigment epitheliopathy. Clin Experiment Ophthalmol. 2006 Nov. 34(8):810-2. [Medline].

Lofoco G, Ciucci F, Bardocci A, Quercioli P, Steigerwalt RD Jr, De Gaetano C. Optical coherence tomography findings in a case of acute multifocal posterior placoid pigment epitheliopathy (AMPPPE). Eur J Ophthalmol. 2005 Jan-Feb. 15(1):143-7. [Medline].

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O’Halloran HS, Berger JR, Lee WB, Robertson DM, Giovannini JA, Krohel GB, 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. [Medline].

Parmeggiani F, Costagliola C, D’Angelo S, Incorvaia C, Perri P, Sebastiani A. Clear cell renal cell carcinoma associated with bilateral atypical acute posterior multifocal placoid pigment epitheliopathy. Oncology. 2004. 66(6):502-9. [Medline].

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Uthman I, Najjar DM, Kanj SS, Bashshur Z. Anticardiolipin antibodies in acute multifocal posterior placoid pigment epitheliopathy. Ann Rheum Dis. 2003 Jul. 62(7):687-8. [Medline].

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El-Markaby HS, Mohammed TH, El-Raggal TM. Acute posterior multifocal placoid pigment epitheliopathy: role of TNF blocker in severe cases. Retina. 2012 Nov-Dec. 32 (10):2102-7. [Medline].

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Lakshmana M Kooragayala, MD Vitreo-retinal Surgeon, Marietta Eye Clinic

Lakshmana M Kooragayala, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

R Christopher Walton, MD Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, University of Tennessee College of Medicine

R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Retina Society, American College of Healthcare Executives, American Uveitis Society

Disclosure: Nothing to disclose.

C Stephen Foster, MD, FACS, FACR, FAAO, FARVO Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution

C Stephen Foster, MD, FACS, FACR, FAAO, FARVO is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Association of Immunologists, American College of Rheumatology, American College of Surgeons, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, American Uveitis Society, Association for Research in Vision and Ophthalmology, Massachusetts Medical Society, Royal Society of Medicine, Sigma Xi

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Aldeyra Therapeutics (Lexington, MA); Bausch & Lomb Surgical, Inc (Rancho Cucamonga, CA); Eyegate Pharma (Waltham, MA); Novartis (Cambridge, MA); pSivida (Watertown, MA); Xoma (Berkeley, CA)<br/>Received research grant from: Alcon; Aldeyra Therapeutics; Allakos Pharmaceuticals; Allergan; Bausch & Lomb; Clearside Biomedical; Dompé pharmaceutical; Eyegate Pharma; Mallinckrodt pharmaceuticals; Novartis; pSivida; Santen.

Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous coauthor, James P Ganley, MD, PharmD, DrPH, to the development and writing of this article.

Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)

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