This prospective, single-center case-control study aimed to investigate the association between pseudoexfoliation syndrome (PES) and carpal tunnel syndrome (CTS) using biochemical markers. A total of 159 participants aged 50-80 years were categorized into PES, CTS, and control groups. Diagnoses were confirmed by slit-lamp biomicroscopy for PES and electrophysiological evaluation (EMG) for CTS. Serum biomarkers, including homocysteine, methylmalonic acid, paraoxonase-1 (PON1), homocysteine thiolactonase (HTLase), and matrix metalloproteinases (MMP-2 and MMP-9), were measured. Group comparisons, diagnostic performance (ROC analysis), and independent associations (multinomial logistic regression) were evaluated. Comorbidities were recorded and analyzed in subgroup analyses.

Pseudoexfoliation syndrome (PES) is a systemic disorder characterized by the accumulation of extracellular fibrillar material in ocular and extraocular tissues. It has been associated with extracellular matrix dysregulation, oxidative stress, and vascular dysfunction, and may involve systemic manifestations beyond the eye. Previous studies have suggested links between PES and several systemic conditions, including cardiovascular disease, metabolic disorders, and neurodegenerative processes.

Carpal tunnel syndrome (CTS), the most common entrapment neuropathy, results from compression of the median nerve at the wrist and is influenced by both local mechanical factors and systemic conditions such as obesity, diabetes mellitus, and metabolic syndrome. Emerging evidence suggests that metabolic and inflammatory mechanisms, including dyslipidemia and oxidative stress, may contribute to peripheral nerve dysfunction.

Although both PES and CTS have been associated with systemic and metabolic disturbances, the extent to which they share common pathophysiological mechanisms remains unclear. In particular, alterations in homocysteine metabolism, oxidative stress pathways, and extracellular matrix remodeling may represent overlapping biological processes.

This prospective, case-control study was designed to evaluate the association between PES and CTS by comparing three groups: patients with PES, patients with CTS, and control subjects. Serum biomarkers related to homocysteine metabolism (homocysteine, methylmalonic acid), enzymatic activity (paraoxonase-1 and homocysteine thiolactonase), and extracellular matrix turnover (MMP-2 and MMP-9) were analyzed. The study also aimed to assess the coexistence of PES and CTS and to explore potential shared systemic mechanisms underlying both conditions.

Inclusion Criteria:

• Being between the ages of 50-80
• Having been diagnosed with PES during routine eye examination

Exclusion Criteria:

• History of major hand-wrist trauma or surgical intervention
• Acromegaly
• Presence of any structural abnormality in bone structure
• Pregnancy
• Gout
• Rheumatoid arthritis
• Connective tissue disease
• Acromegaly
• Thoracic outlet syndrome
• Brachial plexopathy
• Cervical disc herniation
• Presence of cardiac pacemaker
• Steroid users
• Repetitive hand operations

Case group participants will be selected from patients diagnosed with PES during eye examination. After informed consent, EMG will be performed to evaluate for CTS. Boston CTS Questionnaire will assess symptom severity in CTS-positive patients. Demographics, comorbidities, EMG and questionnaire results will be recorded. Control group will consist of age/gender-matched patients with mechanical back, knee, or hip pain without CTS symptoms. They will also undergo EMG after consent. All demographic data, comorbidities, and EMG results will be documented for both groups.

The collected individual patient data contains sensitive personal health information protected by privacy regulations. Due to ethical considerations and patient confidentiality requirements specified in our informed consent protocol, we are unable to share the raw individual patient data with other researchers. However, aggregated and anonymized statistical results will be made available through scientific publication.