Targeting Macular Pigment in Intermediate Age-Related Macular Degeneration: Oral Supplementation Versus Transscleral Iontophoresis in a Prospective Pilot Study

Background/Objectives: Macular pigment optical density (MPOD) represents a biomarker of retinal antioxidant status in intermediate age-related macular degeneration (iAMD). Strategies aimed at increasing macular carotenoid availability may contribute to disease stabilization. This study evaluated the effects of oral supplementation and transscleral iontophoresis on MPOD and retinal parameters in iAMD. Methods: This prospective, non-randomized pilot study included 60 eyes of 60 patients with intermediate AMD enrolled at the Eye Clinic of the University of Naples Federico II between July 2024 and May 2025 (ClinicalTrials.gov NCT06465342). Patients received either oral carotenoid supplementation (n = 30) or transscleral iontophoresis (n = 30). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and MPOD measured by one-wavelength reflectometry ( Visucam 200; Carl Zeiss Meditec, Jena, Germany) were assessed at baseline and 6 months. Results: BCVA remained stable in both groups without significant changes (p > 0.05). MPOD significantly increased in the iontophoresis group (0.40 ± 0.11 to 0.49 ± 0.12, p < 0.001) with no statistically significant difference between them (p = 0.09). CMT showed a mild, non-significant increase in both groups (p > 0.05). No adverse events were observed. Conclusions: Both oral supplementation and transscleral iontophoresis were associated with a significant increase in MPOD while preserving visual acuity in intermediate AMD. Within the limitations of this non-randomized pilot study, transscleral iontophoresis produced MPOD changes comparable to those observed with oral supplementation. These findings are exploratory and support further investigation of localized delivery strategies in larger, randomized trials.