What is the management approach for a patient presenting with acute symptoms of Chronic Progressive External Ophthalmoplegia (CPEO)?

Management of Acute Symptoms in Chronic Progressive External Ophthalmoplegia (CPEO)

Patients presenting with acute symptoms of Chronic Progressive External Ophthalmoplegia (CPEO) should be treated as a medical emergency and referred immediately to an emergency department or stroke center for neurological evaluation due to the high risk of concurrent cerebrovascular events.

Initial Assessment and Urgent Management

• CPEO patients presenting with acute symptoms require prompt evaluation as they may represent an important clinical indicator of an embolic, inflammatory, or other process requiring urgent systemic medical evaluation 1
• Acute symptoms in CPEO patients may mask underlying cerebrovascular events, as demonstrated in case reports where patients with baseline ophthalmoplegia experienced strokes without typical ocular manifestations 2
• Diffusion-weighted MRI should be performed urgently (within 24 hours) as silent brain infarction is frequently present in patients with acute ocular symptoms 1

Diagnostic Workup for Acute Presentations

• Evaluate for signs of giant cell arteritis (GCA) in patients over 50 years of age, including temporal tenderness, jaw claudication, weight loss, proximal myalgia, or fever 1
• Order C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) tests, which are typically elevated in GCA 1
• Perform comprehensive neurovascular assessment, as up to 24% of patients with acute ocular symptoms may have concurrent cerebrovascular accidents on diffusion-weighted MRI 1
• Consider genetic testing for mitochondrial DNA mutations in patients with unclear etiology of symptoms, as multiple genes (POLG, RRM2B, ANT1, PEO1/TWNK) are implicated in CPEO 2, 3

Treatment Approach

For Suspected Vascular Etiology:

• If GCA is suspected, initiate prompt systemic corticosteroid therapy to prevent vision loss in the fellow eye or vascular occlusion elsewhere 1
• Refer for stroke center evaluation within 24 hours of symptom onset, as the risk of stroke is highest within the first 7 days and remains elevated for 30 days 1
• Consider hyperbaric oxygen therapy (100% oxygen over 9 hours) which has demonstrated efficacy over observation alone in several small randomized trials for retinal artery occlusions 1

For Mitochondrial Disease Management:

• Address ptosis symptoms which are often the first and most disabling manifestation of CPEO 4, 5
• Consider frontalis suspension surgery using monofilament synthetic material for ptosis correction, adjusted to provide linkage between eyebrow and eyelid while allowing eyelid closure when frontalis muscle is relaxed 5, 6
• Avoid conventional ptosis surgery which may induce lagophthalmos and exposure keratitis in CPEO patients 5

Follow-up Care

• Monitor for development of iris or retinal neovascularization; if present, consider panretinal photocoagulation (PRP) with or without anti-vascular endothelial growth factor (anti-VEGF) therapy 1
• Identify and optimize control of chronic systemic diseases (e.g., diabetes, hypertension, lipid disorders) which are common comorbidities in CPEO patients 1, 3
• Establish effective communication with the patient's primary care physician about the status of the ocular disease and its relation to systemic disease 1

Important Considerations and Pitfalls

• Diplopia may be more frequent in CPEO than previously assumed, and should be carefully assessed 4
• Ptosis in CPEO may initially be unilateral or asymmetric, leading to delayed diagnosis; consider CPEO in the differential diagnosis of etiologically unclear acquired ptosis 4, 6
• Intraoperative abnormal observations during ptosis surgery and postoperative motility problems may be signs of previously undiagnosed CPEO 6
• A new significant systemic cardiovascular condition (typically clinically significant carotid stenosis) is discovered in up to 70% of patients with symptomatic acute ocular vascular events 1