Histologic Findings after Amniotic Membrane Graft in the Human Cornea Oscar Gris, MD, 1,2 Charlotte Wolley-Dod, MD, 2 Jose´ L. Gu¨ell, MD, 1 Francesc Tresserra, MD, 3 Enrique Lerma, MD, 4 Borja Corcostegui, MD, 1 Alfredo Ada´n, MD 1,2 Objective: To describe the histopathologic findings in the human cornea several months after a stromal amniotic membrane graft. To show the clinicopathologic correlation after the graft in two cases with different follow-up times. Design: Two interventional case reports with clinicopathologic correlation. Participants: Two patients with neurotrophic corneal ulcer unresponsive to medical treatment(one with stromalvascularization and the other without stromal vascularization). Intervention: Amniotic membrane graft was performed in both patients to treat the neurotrophic ulcer. Th and 7 months afteramniotic membrane grafting, a penetrating keratoplasty was needed, and the removed corneas were analyzed. Main Outcome Measures: Clinical and histopathologic examinations, including routine histopathologic and immunohistochemical studies. Results: Complete epithelialization was observed on histologic examination over the basement membran of the amniotic membrane graft. The amniotic membrane was slowly reabsorbed in the cornea without strom vascularization with no inflammatory reaction produced. In the cornea thathad stromalvascularization the amniotic membrane was rapidly reabsorbed because of the presence ofabundantinflammatory cells. Once reabsorbed, the amniotic membrane was replaced by new fibrotic stroma, that was different from that found the rest of the cornea but that helped to maintain corneal thickness. Conclusions: The amniotic membrane graft allows for correctepithelialization in cases of neurotrophic cornealulcer. Once the amniotic membrane is reabsorbed, it is replaced by a new fibrotic stroma, which can reduce corneal transparency. In corneas that have no stromal vascularization, the graft may remain in the st for many months, compromising corneal transparency during this period. Ophthalmology 2002;109:508 –512 © 2002 by the American Academy of Ophthalmology. In recent years the amniotic membrane has been proposed as a useful treatment option for a variety of ocular surface diseases, 1–7 and its clinical use has increased enormously around the world. Its important properties include the ability to favor epithelialization, 1,5,8 and its antiinflammatory and healingeffects. 6,7,9 Theamnioticmembranegrafthas proven to be an effective treatment for noninfectious cor- nealulcers otherwise unresponsive to medical therapy. In these cases the amniotic membrane acts as a basement membrane, favoring an overlying epithelialization, thereby achieving healing with an increase in corneal thickness in areas where thinning has occurred. 1–3 However, we do not know how the amniotic membrane behaves several mont after implantation within the human stroma on a histolog level.We report on the histologic findings in two human corneas, which required penetrating keratoplasty several months after an amniotic membrane graft for the treatm of a neurotrophic corneal ulcer. In the first case there wa stromal vascularization of the cornea, which was remove months after an amniotic membrane graft. In the second case the cornea had considerable stromal vascularization and was removed 7 months after amniotic membrane gra ing. As far as we are aware, there have been no previous reported histologic studies that analyze amniotic membr behavior in the human cornea. Case Reports Patient 1 A 51-year-old man with a single eye was referred to us in Sep- tember 1999 with a total retinal detachment with multiple bre four quadrants. Surgery was performed with the placement of a 4-mm silicone band, pars plana vitrectomy with lensectomy, en- dolaserphotocoagulation, and intraocular silicone oilinjection. Although the retina was attached after surgery, 4 weeks later an Originally received: May 21, 2001. Accepted: August 14, 2001. Manuscript no. 210339. 1 Instituto de Microcirugı ´a Ocular (IMO), Universitat Auto`noma de Bar- celona, Barcelona, Spain. 2 Hospital de la Santa Creu i SantPau,Department of Ophthalmology, Universitat Auto`noma de Barcelona, Barcelona, Spain. 3 Institut Dexeus, Department of Pathology, Barcelona, Spain. 4 Hospital de la Santa Creu i Sant Pau, Department of Pathology, Univer- sitat Auto`noma de Barcelona, Barcelona, Spain. The authors have no proprietary interest in the material presented in this article. Reprintrequests to OscarGris,MD, Instituto de Microcirugı ´a Ocular (IMO),Munner, 10,08022 Barcelona, Spain. 508 © 2002 by the American Academy of Ophthalmology ISSN 0161-6420/02/$–see front matter Published by Elsevier Science Inc. PII S0161-6420(01)00969-1