This research explores the potential of retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs), as biomarkers for predicting response to transcranial magnetic stimulation (TMS) in treatment-resistant depression (TRD). We also aim to assess the impact of TMS treatment on RGCs and ipRGCs in TRD patients, investigating associations with clinical improvements and cognitive status. A clinical trial involving 44 patients with treatment-resistant depression (TRD) will be conducted. All participants will receive rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Data will be collected pre- and post-intervention, as well as at a 2-month follow-up, using multiple outcome measures, including the post-illumination pupil response (PIPR). The project seeks to confirm the effectiveness of TMS and the potential of RGCs/ipRGCs as predictors of treatment response, thereby facilitating the development of personalized treatment strategies for TRD patients undergoing rTMS therapy.
Diagnosis of MDD, confirmed via the structured clinical interview;
TRD type;
Age between 18-65 years;
Visual acuity of 20/32 or better.
Prior rTMS treatment;
Contraindications for TMS;
Psychiatric disorders other than MDD;
Systemic diseases affecting the eyes (e.g., diabetes mellitus);
Single group
Repetitive transcranial magnetic stimulation (rTMS)
DeviceEach participant's resting motor threshold (RMT) will be determined by visual observation in accordance with standard clinical practice. Intermittent theta-burst stimulation (iTBS) will be delivered over the left dorsolateral prefrontal cortex (DLPFC) using these parameters: stimulation intensity 120% RMT; bursts at 50 Hz; 2 s on and 8 s off; 600 pulses per session; total stimulation time approximately 3 minutes per session. Stimulation will be delivered using a MagPro X100 stimulator with MagOption, equipped with a B70 butterfly-shaped coil with static cooling (MagVenture, Denmark). Treatment will comprise 20 sessions, delivered once daily on weekdays.
Chromatic pupillometry
To extract post-illumination pupil response (PIPR) derived from ipRGCs
Optical Coherence Tomography (OCT)
To extract central retinal thickness and thicknesses of retina neuronal layers (GCL-IPL and RNFL)
Pattern Electroretinogram (PERG)
To extract PERG N95 wave related to RGC function.
Contrast sensitivity test
To measure contrast sensitivity
Montgomery-Åsberg Depression Rating Scale (MADRS)
To evaluate treatment response. Scores range from 0 to 60, with higher scores indicating more severe depressive symptoms.
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Polytechnic Institute of Porto
Lead sponsor
Hospital de Sao Joao, Porto
Collaborator
