Acute Effects of Cervical Manual Therapy on Eye Blood Flow

Overview

This study evaluates the acute effects of cervical manual therapy on retinal and choroidal microvascular perfusion using optical coherence tomography angiography (OCTA). In this prospective randomized sham-controlled trial, 100 patients with chronic mechanical neck pain were randomly assigned to receive either cervical high-velocity low-amplitude manipulation combined with Maitland mobilization (manual therapy group) or sham treatment. Bilateral OCTA examinations were performed at baseline and at 15, 30, 60, and 120 minutes after intervention. The primary outcome is whole-image density Secondary outcomes include whole-image and parafoveal vessel density, radial peripapillary capillary (RPC) density, subfoveal choroidal thickness, foveal avascular zone parameters, retinal nerve fiber layer thickness, ganglion cell complex thickness, and macular thickness. The study aims to determine whether cervical manual therapy produces a significant augmentation of retinal and choroidal perfusion compared with sham treatment, with peak effects expected at 60 minutes post-intervention.

Background and Rationale Cervical musculoskeletal disorders, including mechanical neck pain and cervicogenic headache, affect an estimated 30-50% of the general population. Manual therapy encompassing spinal manipulation and mobilization techniques targeting the cervical spine has demonstrated efficacy in reducing pain intensity and improving functional outcomes. However, beyond its established biomechanical and neurophysiological effects, growing interest has emerged in elucidating the potential vascular and autonomic consequences of cervical manual therapy, particularly with respect to ocular circulation. The eye is uniquely positioned as a window into systemic and regional vascular status. The retinal and choroidal vasculature are regulated by a complex interplay of local autoregulatory mechanisms, systemic blood pressure, intraocular pressure, and autonomic nervous system tone. The cervical sympathetic chain, lying in close anatomical proximity to the cervical vertebrae and the carotid artery, provides preganglionic and postganglionic sympathetic innervation to the ocular structures. Mechanical stimulation of the cervical spine may therefore modulate ocular perfusion through sympathetic pathways, alterations in vertebral artery blood flow, or changes in intracranial pressure dynamics. Optical coherence tomography angiography (OCTA) has emerged as a non-invasive, high-resolution imaging modality capable of quantifying retinal and choroidal microvasculature with unprecedented detail. Quantitative metrics derived from OCTA, including vessel density, foveal avascular zone area, and choroidal thickness, provide sensitive and reproducible indices of microvascular status. To date, the effects of cervical manual therapy on ocular circulation have been investigated only sporadically and with methodological limitations, including small sample sizes, absence of bilateral assessment, lack of temporal resolution, and absence of sham or no-treatment control arms. No prior study has employed OCTA to comprehensively evaluate the acute, time-resolved effects of cervical manual therapy across multiple retinal and choroidal vascular compartments in both eyes simultaneously using a sham-controlled design. Objectives The primary objective is to evaluate the acute effects of a single session of cervical manual therapy on retinal and choroidal microvascular perfusion as measured by OCTA in patients with chronic mechanical neck pain. The secondary objectives are: To assess changes in parafoveal vessel density To assess changes in radial peripapillary capillary density To assess changes in subfoveal choroidal thickness To assess changes in foveal avascular zone parameters To assess changes in retinal nerve fiber layer thickness To assess changes in ganglion cell complex thickness To assess changes in macular thickness To evaluate the temporal profile of vascular responses (at 15, 30, 60, and 120 minutes post-intervention) To compare vascular responses between active manual therapy and sham treatment Hypothesis Cervical manual therapy will produce a significantly greater augmentation of retinal and choroidal perfusion compared with sham treatment, with peak between-group differences at 60 minutes post-intervention, followed by convergence toward baseline by 120 minutes. Study Design This is a prospective, single-center, parallel-group randomized sham-controlled trial. Participants are randomly assigned (1:1) to receive either cervical high-velocity low-amplitude manipulation combined with Maitland mobilization (manual therapy group) or sham treatment. Bilateral OCTA examinations are performed at baseline and at 15, 30, 60, and 120 minutes after intervention. Setting The study is conducted at SBU Van Training and Research Hospital, Van, Turkey. Participant Timeline Screening and enrollment: February 2026 Intervention and follow-up: Single session with 120-minute post-intervention observation Final data collection: May 2026 Sample Size Based on published OCTA test-retest data (intraday coefficient of variation \~2.5% for SCP whole-image density; within-subject standard deviation \~1.2 percentage points), a minimum detectable between-group difference of ≥2 percentage points, α=0.05 (two-tailed), and 1-β=0.80, a minimum of 42 participants per group is required. The enrolled sample of 50 per group provides ≥85% power and accommodates an estimated 15% dropout rate. Interventions Manual therapy group: A single, standardized session consisting of cervical HVLA thrust manipulation targeting C1-C2 and C3-C4 bilaterally, supplemented by sustained Maitland grade III-IV mobilization of the mid-cervical spine. Total session duration: 15-20 minutes. Audible cavitation is documented as a quality indicator. Sham control group: Light, non-therapeutic manual contact at the same anatomical sites without joint movement, traction, or thrust (\<5 N contact force). Session duration identical to active intervention. Both groups remain seated throughout the observation window to control for postural effects on choroidal thickness. Outcome Measures Primary outcome: "Primary outcome was right-eye SCP whole-image density Secondary outcomes: whole-image and parafoveal vessel density Radial peripapillary capillary optic disc density Subfoveal choroidal thickness (μm) Foveal avascular zone area, perimeter, and circularity Retinal nerve fiber layer global thickness Ganglion cell complex thickness Macular center thickness Signal strength index Data Collection OCTA imaging is performed with a spectral-domain OCT device (Optovue Solix, Visionix / Optovue, Inc., Fremont, CA, USA) at T0, T15, T30, T60, and T120 minutes post-intervention by the same blinded technician. Protocols include 6×6 mm foveal-centered and 4.5×4.5 mm optic disc-centered scans. Only images with SSI ≥6 are included. To mitigate repeated-scan artifacts, the same automated segmentation algorithm is applied uniformly across all time points, and all segmentations are manually verified by a masked grader. Participants undergo a 2-minute dark adaptation prior to each scan, and the built-in eye-tracking system is activated. Scan registration across time points is performed using the device's automated follow-up mode. Statistical Analysis Statistical analyses use Python 3.11 (SciPy 1.11, pandas 2.1, pingouin 0.5.4, statsmodels 0.14). Normality is assessed using the Shapiro-Wilk test. Within-group temporal changes are analyzed using the Friedman test; post-hoc Wilcoxon signed-rank tests with Bonferroni correction are applied. Between-group differences are analyzed using linear mixed-effects models with random intercept for subject and random slope for time, including fixed effects for group, time, and group×time interaction. Benjamini-Hochberg FDR correction is applied across all secondary outcomes. Analysis is performed on both intention-to-treat (ITT) and per-protocol (PP) basis. Adverse Event Monitoring All participants are monitored for adverse events throughout the study period (from randomization through 24 hours post-intervention). Participants are asked at T15, T30, T60, T120, and via telephone at 24 hours about the occurrence of: neck pain worsening, dizziness, headache, nausea, visual symptoms (blurred vision, floaters, photopsia), or any other unusual symptom. All events are recorded and graded for severity and relationship to intervention.