Association of optic disc drusen and small scleral canals - A systematic review and meta-analysis.

The pathophysiology of optic disc drusen (ODD) has long been discussed. According to one leading theory, they develop from calcified mitochondria extruded from axons compressed by an unusually small scleral canal. To examine this hypothesis, we conducted a systematic review and meta-analysis evaluating the scleral canal size in patients with ODD (PO) in comparison to healthy subjects (HS). We searched MEDLINE, Cochrane Central, EMBASE and gray literature to identify relevant articles. A subgroup analysis compared patients with buried ODD (PO_b) and patients with visible ODD (PO_v). The study was registered with the International Prospective Register of Systematic Reviews on December 9th, 2022 (Registration: CRD42022375110). We included fifteen articles in the review and fourteen in the meta-analysis. The mean diameter of the scleral canal computed using both fundus photography (D_F) and spectral-domain with enhanced depth imaging optical coherence tomography (D_O-EDI) was significantly smaller in PO compared to HS (standardized mean difference -1.21 [-1.85 to -0.56] and -0.66 [-0.94 to -0.37] respectively). D_O-EDI, but not D_F, was higher in PO_v as compared to PO_b. When including all-generation OCT in the analysis, the difference between PO_v and PO_b, but not between PO and HS, remained. Several intertwined hypotheses can explain these subgroup and sensitivity results: an enlargement of the canal as the ODD grow, an enlargement with time, or a measurement bias (artefactual enlargement of the canal due to a posterior shadow on OCT). In conclusion, this review and meta-analysis further supports the role of a small scleral canal in the development of ODD.