Acute Multifocal Placoid Pigment Epitheliopathy Clinical Presentation
- Author: Lakshmana M Kooragayala, MD; Chief Editor: Hampton Roy, Sr, MD more...
Prodromal symptoms may include the following:
Prior viral or flulike syndrome - Occurs in approximately one third of patients; symptoms include fever, cough, swollen lymph glands, nausea, vomiting, myalgia, malaise, muscle and joint tenderness
Neurologic symptoms (rare) - Transient aphasia, numbness and weakness of extremities, feelings of clumsiness
Early-stage symptoms may include the following:
Acute decrease in visual acuity
Conjunctival injection/episcleritis (rare)
Late-stage symptoms may include the following:
Mild visual impairment (20/25 to 20/40), common
Significant visual loss (20/200), rare
Patients should have a complete eye examination, including visual acuity, pupillary reactions, slit lamp examination, and dilated indirect ophthalmoscopy.
Visual acuity may be normal; if the macula is involved, vision can decrease to 20/200 within days after onset.
Extraocular muscle function is normal unless cerebral vasculitis develops.
No relative afferent pupillary defect is present.
Conjunctivitis or episcleritis is rarely present.
If present, anterior chamber reaction usually is mild, although fibrinous inflammation has been noted.
Vitreous cells may be found in up to 50% of eyes that are affected, but it is usually mild if present.
Retinal findings are the main feature of the disease.
Multiple subretinal placoid yellow-white lesions are seen in both eyes. In some cases, the lesions are unilateral with involvement of the second eye either within a short period of time or after an extended period. New lesions may occur in the affected eye as old lesions begin their resolution.
Rarely, a well-demarcated serous retinal detachment may develop in the posterior retina and rarely located anterior to the equator.
Optic nerve involvement
Blurring of disc margins, hyperemia, edema, and superficial hemorrhages may be found.
Papillitis and optic neuritis are a less frequent occurrence.
Venous compression within the optic nerve may lead to retinal vein distension and, rarely, to central retinal vein occlusion.
Individual placoid lesions resolve over several weeks as a natural course, along with other signs of inflammation.
Resolution of the placoid lesions is characterized by well-demarcated areas of retinal pigment epithelial loss with presence of diffuse fine foci of hyperplasia, along with similar choroidal findings.
Long-term retinal pigment epithelium (RPE) changes may continue to develop long after recovery.
In most instances, the visual acuity returns to 20/30 or better; initial visual recovery is rapid, but final recovery may take up to 6 months.
APMPPE tends to occur bilaterally, although both eyes may not be affected at the same time.
Long-term follow-up studies suggest that recurrences may develop in up to 50% of patients.
Systemic manifestations, believed to result from diffuse multisystem vasculitis, may include the following:
Neurologic manifestations include cerebral vasculitis, transient ischemic attacks, fixed neurologic deficits, transient or permanent low-tone hearing loss, vertigo, labyrinthitis, and meningoencephalitis.
Rare ocular manifestations
These may include the following:
Perilimbal corneal stromal infiltrates
Serous retinal detachment
Retinal venous dilation and tortuosity
Limbal corneal neovascularization
Limbal corneal thinning
Anterior and posterior synechiae
Relative afferent pupillary defect
APMPPE has been known to occur after different conditions or in conjunction with a broad variety of disorders, as follows:
Hepatitis B vaccination
Group A streptococcal infection
Swine flu vaccination
Tuberculin skin testing
Adenovirus 5 infection
Use of oral contraceptives
Use of hormone replacements
Clear cell renal cell carcinoma
Systemic necrotizing vasculitis
Meningococcal C conjugate vaccine 
Influenza vaccination 
Varicella vaccination 
The actual cause of APMPPE is not known. Approximately one third of patients in some series have a history of recent viral illness with a flulike syndrome, upper respiratory infection, or other systemic illness several days to a few weeks before appearance of the ocular lesions. Fever, headache, malaise, gastrointestinal, or upper respiratory symptoms may be preceding symptoms.
Since APMPPE seems to occur after diverse infectious diseases and other stimuli, many investigators believe that it is likely an immune disorder. A higher frequency of human leukocyte antigen B7 (HLA-B7) and human leukocyte antigen DR2 (HLA-DR2) have been reported, suggesting an inherited tendency for the disorder, and that several infectious agents and or other triggers may be the stimulus of APMPPE in susceptible individuals. The general consensus is that the systemic and ocular causes of APMPPE may be a generalized vasculitis leading to choroidal lobular nonperfusion.
Choroidal neovascularization can develop in areas of previously healed lesions associated with bleeding and/or subretinal fluid. If the lesion is close to or under the foveal system, patients can experience sudden vision decrease.
Gass JD. Acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol. 1968 Aug. 80(2):177-85. [Medline].
Yang DS, Hilford DJ, Conrad D. Acute posterior multifocal placoid pigment epitheliopathy after meningococcal C conjugate vaccine. Clin Experiment Ophthalmol. 2005 Apr. 33(2):219-21. [Medline].
Mendrinos E, Baglivo E. Acute posterior multifocal placoid pigment epitheliopathy following influenza vaccination. Eye (Lond). 2010 Jan. 24(1):180-1. [Medline].
Fine HF, Kim E, Flynn TE, Gomes NL, Chang S. Acute posterior multifocal placoid pigment epitheliopathy following varicella vaccination. Br J Ophthalmol. 2010 Mar. 94(3):282-3, 363. [Medline].
Baxter KR, Opremcak EM. Panretinal acute multifocal placoid pigment epitheliopathy: a novel posterior uveitis syndrome with HLA-A3 and HLA-C7 association. J Ophthalmic Inflamm Infect. 2013 Feb 4. 3(1):29. [Medline]. [Full Text].
Grkovic D, Oros A, Karadžic J, Bedov T, Gvozdenovic L, Jovanovic S. Acute posterior multifocal placoid pigment epitheliopathy-retinal "white dot syndrome". Med Glas (Zenica). 2013 Feb. 10(1):194-6. [Medline].
Aoyagi R, Hayashi T, Gekka T, Kozaki K, Tsuneoka H. Multifocal electroretinographic evaluation of macular function in acute posterior multifocal placoid pigment epitheliopathy. Doc Ophthalmol. 2013 Jun. 126(3):253-8. [Medline].
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].
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].
Lowder CY, Foster RE, Gordon SM, Gutman FA. Acute posterior multifocal placoid pigment epitheliopathy after acute group A streptococcal infection. Am J Ophthalmol. 1996 Jul. 122(1):115-7. [Medline].
Mensah E, Vafidis GC. Acute posterior multifocal placoid pigment epitheliopathy in a 7-year-old girl. J Pediatr Ophthalmol Strabismus. 2002 Jul-Aug. 39(4):239-41. [Medline].
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].
Ryan SJ, Maumenee AE. Acute posterior multifocal placoid pigment epitheliopathy. Am J Ophthalmol. 1972 Dec. 74(6):1066-74. [Medline].
Scheufele TA, Witkin AJ, Schocket LS, Rogers AH, Schuman JS, Ko TH, et al. Photoreceptor atrophy in acute posterior multifocal placoid pigment epitheliopathy demonstrated by optical coherence tomography. Retina. 2005 Dec. 25(8):1109-12. [Medline]. [Full Text].
Smith CH, Savino PJ, Beck RW, Schatz NJ, Sergott RC. Acute posterior multifocal placoid pigment epitheliopathy and cerebral vasculitis. Arch Neurol. 1983 Jan. 40(1):48-50. [Medline].
Thomson SP, Roxburgh ST. Acute posterior multifocal placoid pigment epitheliopathy associated with adenovirus infection. Eye. 2003 May. 17(4):542-4. [Medline].
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].
Wolf MD, Folk JC, Panknen CA, Goeken NE. HLA-B7 and HLA-DR2 antigens and acute posterior multifocal placoid pigment epitheliopathy. Arch Ophthalmol. 1990 May. 108(5):698-700. [Medline].
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].