Objective:
To highlight the role of retinal pigment epithelium (RPE) dysfunction in MELAS with retinopathy and emphasize the clinical utility of fundus autofluorescence (FAF) for early detection and monitoring.
Background:
MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a multisystem disorder associated with <25% also exhibiting progressive retinal degeneration. The RPE is highly vulnerable to mitochondrial dysfunction, causing impaired metabolism, defective phagocytosis, and structural instability preceding photoreceptor degeneration and visual decline.MELAS patients appear visually spared because the retina’s mixed energy metabolism, low ocular heteroplasmy, and slow degenerative trajectory mask disease activity until later in disease progression. Fundus photography and optical coherence tomography (OCT) may underestimate early disease, whereas FAF provides a sensitive measure of metabolic stress within the RPE. Abnormal autofluorescence identifies regions at risk for atrophy and functional loss, making FAF a valuable clinical tool.
Design/Methods:
A retrospective case review on patient with genetically confirmed MELAS (MT-TL1 m.3243A>G, 25% heteroplasmy) with cardiomyopathy, seizures, migraine, hearing loss, and diabetes presented with progressively decreasing acuity bilaterally. Ophthalmic examination included fundus photography, OCT, and FAF was performed.
Results:
Fundus photography revealed mild bilateral pigmentary retinopathy. OCT showed ellipsoid zone attenuation, outer retinal thinning, and focal RPE disruption. FAF demonstrated patchy hyper- and hypo-fluorescence corresponding to metabolically stressed and nonfunctional RPE, capturing disease activity not fully appreciated on OCT or photography.
Conclusions:
MELAS retinopathy reflects primary mitochondrial RPE dysfunction that progresses before vision loss is clinically evident. FAF serves as a noninvasive “retinal window” into mitochondrial health, allowing early detection of RPE compromise and monitoring of progression. Early identification of RPE stress may guide patient counseling as well as future therapeutic strategies to preserve RPE function and slow visual decline.Integrating FAF into routine care may help maintain vision and optimize clinical management in MELAS patients.
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