Retinal vein occlusion (RVO), a common retinal vascular disease, is frequently treated with anti-vascular endothelial growth factor (anti-VEGF) agents as first-line therapy. However, anti-VEGF monotherapy lacks neuroprotective effects, primarily targets vascular leakage and neovascularization, and requires frequent long-term injections that impose substantial economic burdens. Combined therapeutic strategies addressing both vascular pathology and neural damage are therefore being explored.
This article describes the protocol for a randomized, outcome-blinded, placebo-controlled clinical trial evaluating mecobalamin (a widely used neuroprotective drug) in combination with anti-VEGF for the treatment of macular edema (ME). A total of 120 eligible RVO patients will be enrolled from the First Affiliated Hospital of Chongqing Medical University. Participants will be randomly assigned (1:1) to an experimental group and a control group. The experimental group will receive conventional anti-VEGF therapy plus oral mecobalamin capsules for 6 months, while the control group will receive the same anti-VEGF treatment plus a placebo for 6 months. All patients will undergo one year of follow-up after initial treatment, with visits at 1, 3, 6, 9, and 12 months.
The primary outcome is the change in central subfield thickness (CST) from baseline to one year post-initial treatment. Secondary outcomes include:
* Change in best-corrected visual acuity (BCVA) from baseline over time, * Capillary density, * Cone photoreceptor distribution characteristics, * Mean light sensitivity and fixation stability, * Serum vitamin B12 levels, * Number of anti-VEGF treatments, * Injection frequency (times per year), * Treatment interval, * Incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
This trial evaluates a novel "neuroprotection + vascular intervention" strategy combining mecobalamin with anti-VEGF therapy. The trial aims to provide high-level evidence for synergistic RVO treatment, with the potential to reduce recurrence rates and improve long-term visual function prognosis.
None
None
Parallel
Anti-VEGF drug
Drugconventional anti-VEGF therapy (intravitreal injections of conbercept 0.5 mg initially once a month for 3 months, followed by on-demand therapy which based on recurrence criteria)
Mecobalamin 5 MG
Drugoral mecobalamin capsules 0.5 mg three times daily for 6 months
Placebo
Drugplacebo capsule with a similar appearance and odor to the mecobalamin capsules three times daily for 6 months
Anatomical indicators-central foveal thickness
the changes in central foveal thickness from baseline to 1 year post initial treatment.The primary outcome is the change in central subfield thickness (CST), measured via spectral-domain optical coherence tomography (SD-OCT), from baseline to 12 months post-initial treatment. CST will be defined as the mean retinal thickness within the central 1-mm diameter subfield of the ETDRS grid (Early Treatment Diabetic Retinopathy Study), automatically segmented and calculated using device software (e.g., Heidelberg Spectralis® or equivalent). All OCT scans will be performed by certified technicians following standardized protocols, including quality control for signal strength (\>7/10), proper centering, and absence of artifacts. Measurements will be verified by masked graders at a central reading center.
Change in best-corrected visual acuity (BCVA)
Change in best-corrected visual acuity (BCVA) from baseline over time (months 1,3,6,9,12), assessed using ETDRS charts at 4 meters under standardized luminance (85-120 cd/m²). BCVA will be quantified as letters read (0-100 scale) following manifest refraction, with scoring adherence to ETDRS standards. All measurements will be performed by masked examiners with central reading center quality control.
capillary density
Changes in capillary density, assessed as vessel density (%) in the superficial and deep retinal capillary plexuses using optical coherence tomography angiography (OCTA). Scans will be acquired with a standardized 3×3 mm or 6×6 mm pattern centered on the fovea, processed with projection artifact removal, and quantified within ETDRS grid subfields. All analyses will undergo quality control and centralized grading.
Cone photoreceptor distribution characteristics
3.The changes in cone photoreceptor mosaic metrics including density (cones/mm2), inter-cone distance (µm), and hexagonal packing (%) will be assessed using AO ophthalmoscopy centered at the fovea. Images will be processed with semi-automated cone identification algorithms and compared against normative databases.
Mean light sensitivity and fixation stability
The changes in mean light sensitivity (dB) and fixation stability (% P1, BCEA 63%) will be assessed using microperimetry (68-point central 10°grid, 4-2 staircase strategy) under standardized conditions. Testing requires pupil dilation ≥6 mm, with validity criteria including \<15% false-positive rate and \<20% fixation losses. All analyses will undergo central reading center verification.
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