6 - From Darkness to Light: The History of Retinopathy of Prematurity

Publication Number: 2005.6

Arnav S. Muralidhar, DeBakey High School for Health Professions, Bellaire, TX, United States; Amit R. Bhatt, Baylor College of Medicine, Houston, TX, United States; Ramesh Vidavalur, Weill Cornell Medicine, Ithaca, NY, United States

Background: Retinopathy of Prematurity (ROP) is a vasoproliferative retinal disease of premature infants that emerged as a leading cause of childhood blindness with the advent of neonatal intensive care and improved survival of very low birth weight infants.

Objective: To review the historical evolution of ROP and highlight key discoveries, missteps, and innovations that have shaped modern prevention and treatment strategies.

Design/Methods: Electronic databases (PubMed, MEDLINE, EMBASE, and Google Scholar) were searched for landmark studies, clinical trials, and historical reports related to the pathogenesis, classification, and management of ROP.

Results: ROP was first described by Theodore Terry in 1942 as retrolental fibroplasia (Figure 1). The first epidemic (1940s-1950s) was linked to unrestricted oxygen therapy (Figure 2), a connection identified by Kate Campbell in 1951 (Figure 1), leading to regulated oxygen use. The second epidemic (1970s-1990s) followed advances in neonatal care and improved survival of extremely preterm infants despite cautious oxygen administration. The International Classification of Retinopathy of Prematurity (ICROP; 1984, 1987, 2005) standardized staging, with ICROP 2021 refining severity definitions and treatment criteria. The Cryo-ROP trial (1988) established cryotherapy efficacy, while the LIGHT-ROP trial (1996) introduced laser photocoagulation as a safer alternative. Pierce's 1995 discovery of vascular endothelial growth factor (VEGF) elucidated the molecular basis of neovascularization and led to anti-VEGF therapy. The ETROP trial (2003) redefined treatment thresholds ("type 1" and "type 2" ROP), and the BEAT-ROP trial (2011) validated intravitreal bevacizumab as effective therapy. The SUPPORT (2010) and BOOST II (2013) trials underscored the delicate oxygen balance recognizing lower targets reduced ROP but increased mortality, prompting adoption of intermediate oxygen ranges. A third epidemic, since the early 2000s, now affects low- and middle-income countries where improved preterm survival has outpaced access to screening and treatment.

Conclusion(s): The history of ROP (Table 1) illustrates how therapeutic missteps have driven progress and refined our understanding of the balance between survival and vision. Advances in anti-VEGF therapy, laser photocoagulation, and digital imaging reflect decades of learning from past errors. Looking ahead, telemedicine, artificial intelligence, and predictive analytics promise to transform ROP care from reactive management to proactive prevention, ensuring equitable and sight-preserving neonatal outcomes worldwide.

Table 1. Seminal studies and investigations that have led to discovery, prevention, monitoring, and treatment of ROP.


Figure 1. Portraits of Dr. Campbell and Dr. Terry


Figure 2. An oxygen tent from 1930s