AIM: To clinically differentiate nanophthalmos (NO) and posterior microphthalmos (PM) and to explore the mechanisms related to papillomacular folds (PMF). METHODS: Medical records of 34 unrelated patients with microphthalmos (54 eyes) from April 2009 to October 2017 were retrospectively reviewed. RESULTS: Fourteen eyes of 7 unrelated patients with NO and PM were included in the study. The presenting age of the NO cohort was significantly higher compared with the PM cohort (NO: 27±16y; PM: 3.7±0.6y). PMF was more likely to occur in cases with PM than in NO (25% in NO, 100% in PM). The anatomic features of PMF from optical coherence tomography (OCT) included: ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer and outer nuclear layer. In eyes without an apparent PMF (these were all NO eyes), rudimentary fovea without a foveal pit was noted. Four eyes that were NO developed angle closure glaucoma. Three NO eyes developed exudative retinal detachment and were successfully treated with lamellar sclerectomy. CONCLUSION: Posterior segment changes are pervasive both in PM and NO. Complications like angle closure glaucoma and exudative retinal detachment are likely to occur in eyes with NO but not with PM. Detailed OCT analysis found that PMF was partially a neural retinal issue, suggesting that redundancy of retinal issues involved only inner retinal layers.