Relentless innovation, global collaboration and dedicated specialists are driving a promising future for pediatric retina care, bringing solutions once thought impossible within reach. However, ensuring equitable access and bridging the gap between innovation and implementation remain crucial for realizing this potential for every child.
The parents of a three-month old baby girl had all but given up hope for her left eye. Born with a condition called persistent fetal vasculature (PFV), the vessels within her eye, which typically vanish at birth, remained stubbornly intact, forming a dense white membrane that obscured her vision. To complicate matters, her eye was unusually small, leading even seasoned ophthalmologists to deem it unsalvageable.
In a last-ditch effort, the child’s parents sought help from Prof. Wai-Ching Lam, a pediatric retina specialist from Canada. While hope for the child’s eye was dim, Prof. Lam saw a glimmer of possibility, thanks to recent technological advancements.
“Ultrasound biomicroscopy (UBM) allows us to scan the anterior part of the eye, including the iris and immediately behind it,” Prof. Lam explained. “This is critical in cases like this one because the retina can sometimes develop in aberrant positions. When we go in to clean it up, we might inadvertently create a retinal tear leading to retinal detachment.”
With careful planning and the precision afforded by proper assessment, Prof. Lam was able to identify the areas at risk and successfully remove the obstructive membrane.
“Now, the child is patched and fitted with a contact lens to get some vision in that eye,” he shared. While the restored sight isn’t perfect, it’s functional—providing the small patient with a future her parents never thought possible. “Otherwise, the eye would have been lost, and maybe it would end up having to be removed,” Prof. Lam said.
This case highlights the intricate balance between innovation and expertise in pediatric retina care—a field fraught with unique challenges. For patients like this baby, early and accurate diagnosis is critical, yet it remains one of the most formidable hurdles in managing pediatric retinal conditions.
Diagnosis in a blink
Diagnosing retinal conditions in young children can feel like grueling detective work, especially with squirming little ones. But thanks to advancements in wide-field imaging technology, things have become a bit easier. Clinicians can now capture high-quality retinal images in just a quarter of a second—faster than the blink of an eye.
This leap in technology has also opened doors to early detection. “Retinal screening for neonates can pick up serious conditions like tumors or optic nerve defects that were difficult to pick up before,” Prof. Lam explained.
Artificial intelligence (AI) is now revolutionizing this process further, adding speed and precision to neonatal screening. By integrating AI into diagnostic workflows, images of a child’s retina can be uploaded to the cloud, where the AI system swiftly analyzes them and provides an almost instant assessment.
“AI nails down the diagnosis, and the patient can be referred in a timely fashion with less delays,” noted Prof. Lam. Parents, too, benefit as they no longer endure prolonged periods of uncertainty.
In resource-limited settings, these advancements are particularly transformative. Telemedicine platforms combined with portable fundus cameras enable technicians in rural areas to photograph a baby’s retina and send the images to experts miles away. “They allow us to document changes and share information much more efficiently,” Prof. Lam said. “Before, we had to rely on hand-drawn illustrations, which were quite inaccurate a lot of times.”
Swift and accurate diagnosis lays the groundwork for timely intervention, a critical factor in preventing vision loss in young patients. Early detection means clinicians can choose from an expanding array of treatment options, tailoring care to the child’s unique needs and the specific condition.
From gold standard to game changers
Treating retinal conditions in children is a delicate dance between established techniques and groundbreaking innovations. Today’s clinicians have an expanding arsenal, from tried-and-true therapies like laser photocoagulation for retinopathy of prematurity (ROP) to emerging therapies that push the boundaries of possibility.
Laser photocoagulation, which ablates the peripheral avascular retina, remains the gold standard for managing ROP, halting abnormal blood vessel growth, and preserving vision in preterm infants. However, “children can get quite stressed with lasers and they can go into cardiac arrest,” said Prof. Lam. “About 15 years ago, people started using the anti-vascular endothelial growth factor (anti-VEGF) injections as an alternative treatment to retinopathy and found very successful management.”1
Anti-VEGF drugs like ranibizumab (Lucentis®; Genentech; California, USA) have demonstrated effectiveness in managing aggressive ROP and other vascular conditions. It is less invasive than laser treatment and spares more peripheral retina, which is crucial for a child’s developing vision.
That said, these treatments come with challenges, such as the potential for systemic absorption, which could impact overall development in children. As a result, careful monitoring of patients after treatment is essential to ensure safety and efficacy.1
Surgical interventions for retinal detachment in children have also evolved, driven by innovations in tools and techniques. Pediatric eyes, with their smaller size and developing structures, present unique challenges that traditional instruments cannot address.
“Imagine using the large-sized instruments designed for adults on very small eyes. Your treatment and your efficiency are limited.” Prof. Lam explained. Instruments like 27-gauge vitrectomy tools, compared to traditional 20-gauge ones, allow for precise maneuvers in the smallest of eyes, reducing trauma during surgery and enabling safer, more effective outcomes.2
For complex cases, such as retinal detachment involving proliferative vitreoretinopathy (PVR), surgeons can now employ advanced techniques like scleral buckling combined with pars plana vitrectomy (PPV). These procedures are more refined and tailored to pediatric anatomy, improving the success rates of retinal reattachment in children.3
Beyond surgical and pharmacologic solutions, gene therapy is transforming the landscape of pediatric retina care. This cutting-edge treatment offers the potential for curing inherited retinal diseases (IRDs), not just managing them. “Until five years ago, there wasn’t any treatment for those individuals,” Prof. Lam noted. “Now we can actually replace defective genes and even reverse damage.”
Luxturna® (voretigene neparvovec; Spark Therapeutics, Inc., Pennsylvania, USA), the first FDA approved gene therapy for retinal conditions, targets RP65 mutations associated with Leber congenital amaurosis (LCA). According to Prof. Lam, its approval has opened a floodgate, propagating therapies for other IRDs.
Innovations that inspire
What made Luxturna so revolutionary wasn’t just its ability to treat LCA, but the innovative use of adeno associated virus (AAV) as a delivery system. AAV, known for its ability to infect retinal cells with minimal immune response, opened the door to a wave of new therapies targeting a wider array of genetic retinal conditions.4
AAV vectors are now being explored in clinical trials for a variety of pediatric retinal diseases, such as Stargardt disease and X-linked retinoschisis. Researchers have discovered that AAV2 can effectively reach the inner retina, while AAV8 has shown promise in transducing photoreceptors when delivered subretinally. This ability to target specific retinal cells makes AAV an ideal vehicle for gene therapy, particularly for conditions like retinitis pigmentosa (RP), achromatopsia, and choroideremia.4
One promising development is botaretigene sparoparvovec (botavec; Janssen Pharmaceuticals; Beerse, Belgium), an investigational gene therapy designed to tackle X-linked RP. This treatment delivers functional copies of the RPGR gene to the retina, aiming to restore a stable gene sequence in both rod and cone photoreceptors.5
Recognizing botaretigene sparoparvovec’s transformative potential, regulatory bodies have granted the therapy prestigious designations, including Fast Track and Orphan Drug status from the US Food and Drug Administration (FDA), as well as Advanced Therapy Medicinal Product and Orphan designations by the European Medicines Agency (EMA). Botaretigene sparoparvovec is currently being evaluated in the Phase 3 LUMEOS trial.
In addition to AAV gene therapies, other cutting-edge technologies like clustered regularly interspaced short palindromic repeats (CRISPR) are being explored to repair defective genes directly within the retina. This gene-editing approach has the potential to fix the root cause of genetic retinal diseases at the DNA level.6
Meanwhile, another area of advancement involves gene therapies designed to deliver anti-VEGF treatments. Instead of repeated injections, a single gene therapy like 4D-150 (4D Molecular Therapeutics; California, USA) could enable the eye to produce its own therapeutic agents, effectively transforming it into a self-sustaining ‘drug factory.’7
In other anti-VEGF news, novel agents and delivery methods aim to enhance both efficacy and safety. Long acting anti-VEGF formulations like Eylea® HD (Regeneron Pharmaceuticals; New York, USA) and sustained release implants are in development to reduce the frequency of treatments, a critical advancement for pediatric patients where frequent injections pose risks.
Stem cell therapies are another beacon of hope, aiming to regenerate damaged or degenerated retinal tissue. Induced pluripotent stem cells (iPSCs) and retinal progenitor cells are being explored for their ability to replace lost photoreceptors or support retinal health by restoring retinal pigment epithelial (RPE) cells.8
Clinical trials are underway to test the safety and efficacy of these therapies in conditions like RP and Stargardt disease. Although largely experimental, early results suggest that stem cells could not only halt disease progression but potentially reverse damage in certain cases.9,10
Retinal implants, sometimes referred to as ‘bionic eyes,’ are offering a glimpse into a future where even severe vision loss can be partially restored. These devices, such as the Argus II (Second Sight Medical Products; California, USA) retinal prosthesis system, work by translating visual information into electrical signals that stimulate the remaining retinal cells.
While current implants are limited to providing basic visual functions, like distinguishing light and dark or detecting motion, advancements in microelectronics and bioengineering aim to deliver more detailed visual experiences in the coming years.11
The fight for equity
As science pushes the boundaries of possibility, novel therapies are becoming more accessible, sparking hope in families worldwide. But an unsettling question lingers: Are they truly reaching all children who need them?
For all the groundbreaking progress, the uneven patchwork of global healthcare infrastructure often leaves those in resource-limited settings waiting in the shadows, unable to access these life-changing treatments.
This inequity is starkly evident in the burden of pediatric retinal conditions in developing countries. Here, ROP, trauma-induced retinal damage and untreated congenital disorders cast long shadows over the futures of countless children. These challenges are not merely medical—they are stories of interrupted potential and deferred dreams, underscoring the urgency of delivering solutions to the places where they’re needed most.
“Retinopathy of prematurity is probably one of the more common eye conditions affecting children, particularly causing preventable blindness,” said Prof. Lam. He explained how improving healthcare in low- and middle-income countries has led to what is known as the ‘third epidemic of ROP.’
“These countries were able to keep more premature babies alive, but they didn’t have experience managing this condition before, as they previously didn’t have children surviving,” Prof. Lam noted.
International collaborations are pivotal in addressing these challenges. Organizations like FOCUS Inc. (Illinois, USA) provide training programs and fellowships to empower local specialists. However, sustaining these efforts requires more than just education. Equipment, infrastructure and ongoing support are crucial to creating long-term impact.
“Training somebody is one thing. Supporting them and providing them with the necessary equipment is another,” Prof. Lam highlighted. “In a country where the GDP is low, the question is: How can resources be adequately distributed? Even for well-funded countries, keeping up with the cost of new equipment and advancements is a challenge.”
The global community must also grapple with the broader implications of emerging treatments like gene therapy. “Luxturna, for instance, costs about one million [USD] per dose,” said Prof. Lam. While its potential is transformative, he acknowledged the risk of creating greater inequities. “The excitement of gene therapy is there, but I worry that it will create a greater separation between the haves and have-nots,” he cautioned.
Bridging the gap between innovation and implementation
The future of pediatric retina care is one of promise and perseverance—a journey fueled by relentless innovation, global collaboration and the unwavering commitment of specialists like Prof. Lam. Each breakthrough, whether in advanced imaging, portable diagnostic tools, or gene therapy, edges us closer to a world where no child’s sight is written off as a lost cause.
But the road ahead demands more than scientific triumphs. It calls for equitable access, creative solutions in resource-limited settings and a collective effort to bridge the chasm between innovation and implementation. The stakes are high, but so is the
reward: A child’s ability to see the world, and with it, the limitless possibilities that vision brings.
Editor’s Note: A version of this article was first published in PIE magazine Issue 33.
References
- Wu KY, Wang XC, Anderson M, et al. Innovative use of nanomaterials in treating retinopathy of prematurity. Pharmaceuticals. 2024:17(10);1377.
- Khan MA, Kuley A, Riemann CD, et al. Long-term visual outcomes and safety profile of 27-gauge pars plana vitrectomy for posterior segment disease. Ophthalmology. 2018;125(3):423-431.
- Topcu H, Erdogan G, Alagoz C, et al. The effect of combining scleral buckle surgery with pars plana vitrectomy for treatment of recurrent retinal detachment secondary to proliferative vitreoretinopathy. Beyoglu Eye J. 2023;8(2):91-96.
- Ghoraba HH, Akhavanrezayat A, Karaca I, et al. Ocular gene therapy: A literature review with special focus on immune and inflammatory responses. Clin Ophthalmol. 2022;16:1753-1771.
- Sladen PE, Naeem A, Adefila-Ideozu T, et al. AAV-RPGR gene therapy rescues opsin mislocalisation in a human retinal organoid model of RPGR-associated X-linked retinities pigmentosa. Int J Mol Sci. 2024;25(3):1839.
- Abdelnour SA, Xie L, Hassanin AA, et al. The potential of CRISPR/Cas9 gene editing as a treatment strategy for inherited diseases. Front Cell Dev Biol. 2021;9:699597.
- She K, Su J, Wang Q, et al. Delivery of nVEGFi using AAV8 for the treatment of neovascular age-related macular degeneration. Mol Ther Methods Clin Dev. 2022;24:210-221.
- Radu M, Brănișteanu DC, Pirvulescu RA, et al. Exploring stem-cell-based therapies for retinal regeneration. Life (Basel). 2024;14(6):668.
- Park SS, Bauer G, Fury B, et al. Phase I study of intravitreal injection of autologous CD34+ stem cells from bone marrow in eyes with vision loss from retinitis pigmentosa. Ophthalmol Sci. 2024;5(1):100589.
- Moghadam Fard A, Mirshahi R, Naseripour M, et al. Stem cell therapy in Stargardt disease: A systematic review. J Ophthalmic Vis Res. 2023;18(3):318-327.
- Chuang AT, Margo CE, Greenberg PB. Retinal implants: A systematic review. Br J Ophthalmol. 2014;98(7):852-856.
