Purpose:To investigate possible underlying etiologies of the development of peripheral graft hypertrophic subepithelial opacities (PGHSO) and to evaluate the effects of these opacities on visual outcomes after deep anterior lamellar keratoplasty (DALK).Methods:This prospective, interventional case series enrolled 29 eyes with keratoconus that underwent DALK and developed PGHSO (group 1). The control group consisted of 32 eyes with keratoconus that underwent DALK during the same period and had a clear graft at the final examination (group 2). Possible underlying risk factors for the development of PGHSO were investigated, and postoperative refractive and topographic outcomes were compared between the 2 study groups.Results:Eyes of group 1 had well-defined elevated peripheral subepithelial opacities of the corneal graft, originating from the donor-recipient junction. The central 4-mm area of the graft was clear in all eyes of this group. Compared with the controls, group 1 had flatter grafts at postoperative month 1 and a longer time interval from surgery to initial suture removal. The 2 study groups were comparable in other investigated factors, including the severity of keratoconus, surgical technique, duration of topical steroid use, and donor quality. No significant differences were observed between the case and control groups in postoperative visual acuity and graft surface regularity.Conclusions:Graft flattening during the early postoperative period and prolonged time interval from surgery to initial suture removal might be factors predisposing to the development of PGHSO. This complication did not affect postoperative visual outcomes when the central 4-mm area of the graft remained clear.