eMedicine Specialties > Ophthalmology > Retina

Acute Multifocal Placoid Pigment Epitheliopathy

Author: Lakshmana M Kooragayala, MD, Vitreo-retinal Surgeon, Marietta Eye Clinic
Contributor Information and Disclosures

Updated: May 26, 2009

Introduction

Background

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. 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.

Pathophysiology

The pathophysiology of APMPPE is somewhat speculative, but the basic underlying mechanism is believed to be an obstructive vasculitis, causing nonperfusion of the terminal choroidal lobules in the posterior pole of the eye and inducing secondary ischemic injury of the overlying retinal pigment epithelium and neuroreceptors, which may be partially transient in nature with variable recovery of function.

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.

Frequency

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.

Mortality/Morbidity

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.

Race

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.

Sex

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.

Age

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.

Clinical

History

• Prodromal symptoms
  • 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
  • Moderate-to-severe headache
  • Neurologic symptoms (rare) - Transient aphasia, numbness and weakness of extremities, feelings of clumsiness
• Early stage
  • Acute decrease in visual acuity
  • Blotchy scotomata
  • Photopsia
  • Metamorphopsia/micropsia
  • Photophobia
  • Conjunctival injection/episcleritis (rare)
• Late stage
  • Mild visual impairment (20/25 to 20/40), common
  • Significant visual loss (20/200), rare

Physical

Patients should have a complete eye examination, including visual acuity, pupillary reactions, slit lamp examination, and dilated indirect ophthalmoscopy.

• Early stage
  • 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.
• Late stage
  • 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.
• Recurrences
  • 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)
  • Erythema nodosum
  • Thyroiditis
  • Microvascular nephropathy
  • 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
  • Perilimbal corneal stromal infiltrates
  • Serous retinal detachment
  • Retinal periphlebitis
  • Retinal venous dilation and tortuosity
  • Ciliary flush
  • Corneal edema
  • Limbal corneal neovascularization
  • Limbal corneal thinning
  • Anterior and posterior synechiae
  • Koeppe nodules
  • Relative afferent pupillary defect

Causes

• APMPPE has been known to occur after different conditions or in conjunction with a broad variety of disorders, as follows:
  • Tuberculosis exposure
  • Sarcoidosis
  • Mumps
  • Lyme disease
  • Nephritis
  • Hepatitis B vaccination
  • Group A streptococcal infection
  • Swine flu vaccination
  • Tuberculin skin testing
  • Penicillin therapy
  • Thyroiditis
  • Erythromycin therapy
  • Toxoplasmosis
  • Adenovirus 5 infection
  • Use of oral contraceptives
  • Use of hormone replacements
  • Clear cell renal cell carcinoma
  • Systemic necrotizing vasculitis
  • Ulcerative colitis
  • Meningococcal C conjugate vaccine
  • Adenovirus infection
• 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.

• Search for CME/CE on This Topic »

• White Dot Syndromes (Ophthalmology)