FLORetina 2025: New horizons in research and risk management for ROP

Retinopathy of prematurity (ROP) remains among the most challenging vasoproliferative retinal diseases to manage in pediatric ophthalmology, particularly as advances in neonatal care push the limits of viability and reshape the patient population. This was on display at the FLORetina 2025 Congress, the 13th International Congress on OCT and OCT Angiography (ICOOR), held from December 4-7, in Florence, Italy.

At the meeting, Mary Elizabeth Hartnett, MD, the Michael F. Marmor Professor in Retinal Science and Diseases at Stanford University, delivered a guest lecture titled “The Future: ROP Treatment,” exploring the emerging frontiers in ROP therapy and the evolving ethical, clinical, and technological considerations.

In a conversation with Ophthalmology Times Europe, Hartnett discussed novel approaches in early-phase angiogenic regulation, including small-molecule anti-VEGF agents, IGF-1 modulation, and beta-3 adrenergic receptor pathways. She also highlighted key distinctions in treatment timing and systemic impact, especially when comparing laser therapy with anti-VEGF agents in vulnerable, developmentally immature infants. Importantly, she emphasizes the need for long-term safety studies, particularly in light of VEGF’s role in neural and systemic organ development. Through a clinician-researcher lens, Hartnett provided critical insights into the translational path from experimental findings to safe, effective, and individualized care for infants with ROP.

Editor's note: Transcript edited for clarity and length.

What novel therapies are showing promise for advanced ROP?

Mary Elizabeth Hartnett, MD: A novel and exciting area involves regulating the VEGF pathways to prevent ROP by ordering developmental angiogenesis. This may involve the use of short-acting small agents that are delivered earlier. The design of a study requires some thought since many less severe forms of ROP regress naturally. Also, the premise must be carefully considered and studied before adopting it for safety. There are other potential treatments—prolyl hydroxylase inhibitors, IGF-1, and influencing the beta 3 adrenoceptors.

These treatments may tie into VEGF signaling as well as have independent effects, but appear to be dependent on the phase of ROP when delivered. Nutritional studies, including prenatal ones, may offer promise in the future. We are studying approaches to carefully target the VEGF receptor with the goal of a future treatment that is phase-independent. All these require careful research for safety as well as efficacy.

How do anti-VEGF treatments compare to laser therapy in long-term outcomes?

Hartnett: Studies are suggesting that short half-life anti-VEGF agents may be as safe as laser in the short term as they are to the overall health and neural development of the developing child. However, long-term studies are warranted for the retina and the child.

The studies associating neurocognitive dysfunction with anti-VEGF compared to laser were retrospective analyses from neonatal networks in Canada and the US. Although strong in numbers of infants, they may have had bias, as the sickest infants might have been the ones treated with anti-VEGF. There may be less myopia in anti-VEGF-treated patients as well. The clinical trials support anti-VEGF in the most immature eyes: zone I or posterior zone II. For peripheral zone II eyes, laser and anti-VEGF had similar efficacy for forms of severe ROP.

What are the ethical considerations in using systemic agents for ROP?

Hartnett: The premature infant has organ systems that are not mature—the lung, kidney, gut, and brain, most notably. These systems require vascular support. Intravitreal anti-VEGF agents can enter the bloodstream and potentially be detrimental to the vascular beds of developing organs. VEGF is also a survival factor for neurons and glia as well as vessels. Therefore, there is a concern that injections in the eye may affect the developing premature infant. This concern can also exist for other systemic treatments.

How might gene therapy or regenerative approaches reshape ROP management?

Hartnett: We used gene therapy approaches experimentally as proof of concept, but did not intend that gene therapy would be used in the premature infant. There are risks with the delivery of agents in these very young eyes. There also may not be the need for long-term treatment in ROP, as there appears to be in age-related diseases, such as age-related macular degeneration.

What gaps in evidence remain for current treatment protocols?

Hartnett: I think the most challenging is that ROP continues to evolve as the limits of viability of premature infants are extended. The needs of the extremely low gestational age premature infant and of the developing organ systems likely differ from what we learned from earlier clinical trials when survival of such premature infants was not as common.

There are regional differences worldwide in ROP presentation, also potentially based on genetic differences and resources available for optimized prenatal and newborn care. We are learning that inflammation is an important factor in the extremely low gestational age infant, and other factors may be involved as well.

How do you envision personalized medicine influencing ROP care?

Hartnett: Personalized medicine is an important goal that brings with it much hope. Research is needed into understanding the pathophysiologic factors associated with ROP, including as it evolves, and from the basic laboratory that enables us to study mechanisms of disease. In addition, features from OCT and MRI imaging associated with ROP can be important in learning about the risk of ROP on vision and neural development.

Through analysis with machine learning methods, the prediction of the risk of outcomes may become possible. This would help us with managing screening examinations and potentially provide avenues for testing new treatments.

REFERENCE:

1. Harnett ME. The Future: ROP Treatment. Presented at: FLORetina 2025–International Congress on OCT and OCT Angiography (ICOOR); December 4-7, 2025; Florence, Italy.