Clinical Differentiation of Painful Ophthalmoplegia: A Comparative Analysis of Diagnostic Groups

Objective: Painful ophthalmoplegia (PO) is a clinical syndrome with diverse etiologies, often presenting with overlapping features that complicate diagnosis. Early differentiation is essential to guide appropriate investigations and management. To identify clinical examination findings that differentiate the underlying etiologies of PO and to determine features that may aid in clinical decision-making. Methods: This retrospective observational study included patients with PO evaluated at a tertiary neuro-ophthalmology center between January 2014 and January 2024. Clinical, demographic, and laboratory data were collected. Patients were classified into diagnostic groups based on etiology. Comparative analyses and binary logistic regression were used to identify clinical predictors that distinguish cavernous sinus-orbital apex (CS-OA) inflammatory syndrome from other causes. Results: A total of 94 patients were included. CS-OA (28.7%) and carotid-cavernous fistula (CCF) (26.6%) were the most common etiologies. Ptosis was more frequent in CS-OA and was identified as an independent predictor (p=0.031). Chemosis and vision loss were more common in non-CS-OA etiologies and were independently associated with these conditions (p=0.041 and p=0.018, respectively). Chemosis was observed in 88% of CCF cases. Vision loss was most frequent in infectious etiologies, particularly invasive fungal sinusitis. Facial hypoesthesia showed a trend toward an association with CS-OA (p=0.073). Conclusion: Specific clinical findings, particularly ptosis, chemosis, and vision loss, may help differentiate the underlying etiologies of PO. Careful clinical evaluation can provide valuable guidance for diagnostic decision-making, especially in settings with limited access to advanced investigations.