Extensive Macular Atrophy with Pseudodrusen-like Appearance (EMAP)
Posted inInteresting Papers

Extensive Macular Atrophy with Pseudodrusen-like Appearance (EMAP)

Ophthalmology Board Exam MCQs on EMAP

Ophthalmology Board Exam Practice: EMAP (Extensive Macular Atrophy with Pseudodrusen-like Appearance)

Select one answer per question. Feedback appears immediately after selection.

Question 1: What is the characteristic appearance of macular atrophy in EMAP on short-wavelength autofluorescence?
Correct: C. The document introduces the term “moderately decreased autofluorescence” (MDAF) for EMAP atrophy — a grayish signal darker than surrounding retina but brighter than retinal vessels/optic disc.
Question 2: Which genetic variant has been significantly associated with EMAP?
Correct: C. The C3 rs2230199 variant increases EMAP risk by ~50% and is the only AMD-associated variant significantly linked to EMAP.
Question 3: What is the typical age range for onset of first visual symptoms in EMAP?
Correct: C. Symptom onset is typically between 45 and 60 years (mean presentation age ~62 years).
Question 4: Which OCT finding is considered the hallmark precursor of macular atrophy in EMAP?
Correct: B. Diffuse, relatively hyporeflective RPE–BM separation is the earliest and most consistent precursor lesion in EMAP.
Question 5: What is the typical full-field ERG pattern in most EMAP patients?
Correct: C. EMAP shows generalized photoreceptor dysfunction, predominantly rod, with dramatic recovery of rod responses after prolonged dark adaptation — a key differentiating feature from AMD.
Question 6: Which test best distinguishes EMAP from diffuse-trickling geographic atrophy (DTGA) in AMD?
Correct: B. ERG is nearly always abnormal in EMAP (rod > cone) and normal in AMD-related GA, including DTGA.
Question 7: Which inherited retinal disease shows the strongest phenotypic overlap with EMAP (sub-RPE deposits, temporal involvement, late onset)?
Correct: B. L-ORD (C1QTNF5) is the closest mimic: late onset, sub-RPE deposits, multilobular atrophy, and striking temporal macular involvement (complementary to temporal sparing in EMAP).
Question 8: What is the mean square-root-transformed macular atrophy growth rate in EMAP (pooled Italian + French data)?
Correct: B. Pooled cohort square-root growth rate = 0.447 mm/year — faster than typical AMD GA but comparable to AMD with pseudodrusen.
Question 9: According to the proposed diagnostic criteria, which feature is NOT mandatory for diagnosing EMAP?
Correct: C. Paving stone-like degeneration is highly suggestive but not mandatory (requires UWF imaging and may be absent in some patients).
Question 10: What is the approximate incidence of macular neovascularization in EMAP eyes?
Correct: B. MNV occurs in ~9–15% of EMAP eyes (mostly type 2, subfoveal/juxtafoveal); lower than in DTGA but still clinically significant.

EMAP is a symmetric, rapidly progressive macular atrophy affecting middle-aged individuals (typically onset between 45-60 years), characterized by a clinical triad: vertically oriented macular atrophy (MA) with multilobular borders, pseudodrusen-like deposits across the posterior pole and mid-periphery, and peripheral paving stone degeneration. It is stage-dependent, with novel hallmarks including diffuse separation between Bruch’s membrane (BM) and retinal pigment epithelium (RPE), sparing of the temporal macula, and photoreceptor dysfunction. The review draws on unpublished data from large cohorts (79 Italian and 89 French patients) to describe EMAP as a severely blinding disease with diffuse chorioretinal atrophy. It proposes diagnostic criteria and compares EMAP to age-related macular degeneration (AMD) and inherited retinal diseases (IRDs) to explore pathogenesis. EMAP is often misdiagnosed as AMD, especially in older patients.

Environmental and Genetic Risk Factors

EMAP may involve chronic inflammation and complement pathway abnormalities, with occupational exposure to toxins, family history of glaucoma/AMD, elevated C3 levels, and reduced classical complement activity as potential risks. The C3 rs2230199 variant increases risk by 50%. No AMD risk factors (e.g., smoking, hypertension) are associated. Cases cluster regionally (e.g., post-WWII in France, 1955-1965 in Italy), possibly due to selection bias or environmental factors. Global cases (e.g., Brazil linked to rheumatic fever, Japan as “progressive trickle-like macular degeneration”) suggest autoimmune or toxic etiologies. Prospective studies and pangenomic analyses are recommended.

Clinical Presentation

Symptoms include photophobia, night blindness (nyctalopia), dyschromatopsia, or scotoma, but not metamorphopsia (unlike AMD). Best-corrected visual acuity (BCVA) varies widely (20/20 to light perception) based on foveal involvement. Associated with myopia (77% in French cohort). Mean age at presentation is 62.2 years, with a normal distribution (56-69 years peak). Late presentations risk AMD misdiagnosis; no strict age threshold differentiates them.

Hallmarks on Multimodal Retinal Imaging

  • Macular Atrophy (MA): Bilateral, symmetric, starts superior parafoveal, enlarges vertically, becomes “leaf-shaped” with temporal sparing. On short-wavelength autofluorescence (SW-AF), shows “moderately decreased autofluorescence” (MDAF, “grayish” signal). Near-infrared autofluorescence (NIR-AF) shows diffuse loss; quantitative autofluorescence (qAF) unexplored but promising. Infrared reflectance highlights hyper-reflective atrophy; MultiColor aids pseudodrusen detection.
  • RPE-BM Separation: Hallmark precursor to MA; thick hyporeflective material on optical coherence tomography (OCT), possibly basal laminar deposits (BLamD). Transitions to complete RPE and outer retinal atrophy (cRORA).
  • Pseudodrusen-like Deposits: Reticular yellowish lesions; on OCT, hyperreflective above RPE. Includes subretinal drusenoid deposits (SDDs) in macula (“dot” and “ribbon” types).
  • Paving Stone-like Degeneration: Peripheral atrophy, infero-temporal, symmetric; progresses independently of MA. Visible on ultra-widefield (UWF) imaging.
  • Other Findings: Subretinal fibrosis (up to 2/3 eyes), BM ruptures (linear streaks), hyperreflective pyramidal structures (HPS, calcified debris), choroidal thinning/caverns.
  • Neovascular Complications: Macular neovascularization (MNV) in 9-15% eyes (mostly type 2, subfoveal); 4-year incidence 15.2%. Fluorescein/ICG angiography shows hyperfluorescence in atrophy; OCT angiography (OCTA) reveals choriocapillaris deficits.

Natural History

  • Visual Acuity: Declines ~7.5 ETDRS letters/year; 50% reach ≤20/200 within 4 years post-diagnosis.
  • Visual Field: Kinetic perimetry monitors peripheral defects and temporal sparing islands.
  • MA Growth Rate: Median baseline area 12.61 mm²; square root transformed growth ~0.447 mm/year (faster than AMD GA, similar to diffuse-trickling GA [DTGA]).

Retinal Function

  • Full-Field ERG: Generalized photoreceptor dysfunction (80-90% rod attenuation, milder cone); rod recovery after prolonged dark adaptation suggests visual cycle slowdown.
  • Microperimetry: Mesopic sensitivity decreases with stage; severe rod impairment in early stages.

Phenotypic Overlap with AMD

EMAP resembles DTGA (aggressive AMD GA subtype): MDAF on SW-AF, RPE-BM separation, fast growth (~3 mm²/year), pseudodrusen. Differences: EMAP lacks drusen, has earlier onset, rod dysfunction on ERG (normal in AMD), lower MNV (9-15% vs. 25-33%). Reticular pseudodrusen (RPD/SDDs) in AMD link to rod impairment, mirroring EMAP; may share pathways but EMAP not age-dependent.

Phenotypic Overlap with IRDs

EMAP mimics IRDs with visual cycle impairments (e.g., fundus albipunctatus [RDH5], retinitis punctata albescens [RLBP1]: SDDs, rod dysfunction) and BM diseases (Sorsby fundus dystrophy [SFD, TIMP3]: sub-RPE deposits, MNV; late-onset retinal degeneration [L-ORD, C1QTNF5]: temporal atrophy, deposits; pseudoxanthoma elasticum [PXE, ABCC6]: BM ruptures, temporal sparing). Sub-RPE deposits hinder retinoid transport, causing secondary visual cycle slowdown. Genetic testing excludes IRDs.

A Novel Retinopathy and Diagnostic Criteria

EMAP is panretinal, not just macular. Key messages: Bilateral MDAF MA without drusen prompts investigation; ERG differentiates from AMD. Proposed criteria (bilateral):

  1. Diffuse SDDs/pseudodrusen-like deposits.
  2. Macular findings: RPE-BM separation (pre-atrophic), MDAF MA with separation, or typical “leaf-shaped” MA with temporal sparing.
  3. Negative IRD genetic testing. Paving stone degeneration/ERG alterations supportive but not mandatory.

Therapeutic Implications and Conclusions

No treatments; complement inhibitors (e.g., pegcetacoplan) for AMD GA may apply if EMAP patients were included in trials (C3 link). Future: Histopathology, etiology studies, trials. EMAP is under-recognized, blinding, with potential AMD/IRD overlap.

Citation: Antropoli, Alessio, et al. “Extensive macular atrophy with pseudodrusen-like appearance (EMAP) clinical characteristics, diagnostic criteria, and insights from allied inherited retinal diseases and age-related macular degeneration.” Prog. Retin. Eye Res., vol. 104:101320., Jan. 2025, doi:10.1016/j.preteyeres.2024.101320.

0 0 votes
Article Rating
Subscribe
Notify of
0 Comments
Inline Feedbacks
View all comments