Aniridia, a rare congenital disease, is often characterized by a progressive, pronounced limbal insufficiency and ocular surface pathology termed aniridia-associated keratopathy (AAK). Due to the characteristics of AAK and its bilateral nature, clinical management is challenging and complicated by the multiple coexisting ocular and systemic morbidities in aniridia. Although it is primarily assumed that AAK originates from a congenital limbal stem cell deficiency, in recent years AAK and its pathogenesis has been questioned in the light of new evidence and a refined understanding of ocular development and the biology of limbal stem cells (LSCs) and their niche. Here, by consolidating and comparing the latest clinical and preclinical evidence, we discuss key unanswered questions regarding ocular developmental aspects crucial to AAK. We also highlight hypotheses on the potential role of LSCs and the ocular surface microenvironment in AAK. The insights thus gained lead to a greater appreciation for the role of developmental and cellular processes in the emergence of AAK. They also highlight areas for future research to enable a deeper understanding of aniridia, and thereby the potential to develop new treatments for this rare but blinding ocular surface disease.

无虹膜症是一种罕见的先天性疾病，通常以进行性、明显的角膜缘功能不全和眼表病变为特征，称为无虹膜症相关角膜病变 (AAK)。由于 AAK 的特征及其双侧性质，临床管理具有挑战性和复杂性，因为无虹膜症中存在多种眼部和全身并发症。尽管主要假设 AAK 起源于先天性角膜缘干细胞缺乏症，但近年来，鉴于新证据和对眼部发育和角膜缘干细胞 (LSCs) 生物学的深入了解，AAK 及其发病机制受到质疑。他们的利基市场。在这里，通过巩固和比较最新的临床和临床前证据，我们讨论了有关对 AAK 至关重要的眼部发育方面的关键未回答问题。我们还强调了关于 LSC 和眼表微环境在 AAK 中的潜在作用的假设。因此获得的见解导致对发育和细胞过程在 AAK 出现中的作用有了更大的认识。他们还强调了未来研究的领域，以便更深入地了解无虹膜，从而有可能为这种罕见但致盲的眼表疾病开发新的治疗方法。