Posterior microphthalmia related to PRSS56 variants in a Saudi cohort: a longitudinal study of visual function

To report clinical, multimodal imaging, electrophysiologic, and genetic findings in a cohort of patients with posterior microphthalmia (PM), with emphasis on long-term visual function, a feature rarely addressed in current literature.

This retrospective, longitudinal case series was conducted at King Fahd Armed Forces Hospital, Jeddah, Saudi. Arabia. Six patients from 4 consanguineous Saudi families were followed for 2-16 years (median, 10); 2 more patients had only single visits. All underwent comprehensive ophthalmologic evaluations, including best-corrected visual acuity (BCVA), in logMAR, cycloplegic refraction, intraocular pressure, quantitative color vision testing, fundus examination, multimodal imaging (OCT, fundus autofluorescence, photography), and full-field electroretinography (ffERG). Genetic testing was performed clinically using next-generation sequencing.

All patients showed hallmark PM features: high hyperopia (+12.00 D to +17.75 D), short axial length (12.2-16.4 mm), papillomacular folds, foveoschisis, and EZ disruption. OCT consistently revealed structural anomalies; ffERG responses varied by age. Color vision was preserved, and only mild visual field depression was observed in some patients. BCVA remained relatively stable over time, with limited improvement after age 5. Genetic testing identified pathogenic homozygous PRSS56 variants, including c.1066dup, c.388T>G, and a novel nonsense variant c.1405G>T p.(Glu469∗).

This PM case series highlights the role of early diagnosis and genetic testing in managing PM, especially in consanguineous populations.