Rare Disease Day: An abundance of research Is underway to address rare eye diseases

February 28 is Rare Disease Day, but that name actually is probably a misnomer. According to the National Organization for Rare Disorders (NORD) “One out of every 10 Americans is living with a rare disease. Worldwide, there are more than 300 million people with rare diseases.”¹

In Canada, inherited retinal diseases (IRDs) are estimated to affect 22,000 Canadians.²

Despitethe frequency of these diseases, the affected patients and families are under the radar. According to NORD they are isolated and not receiving answers to their medical questions.¹

Organizations such as Fighting Blindness Canada and NORD are shedding light on this patient population.

Rare eye disease research

Here is some of what is ongoing in this arena. All of this research follows the approval of Luxturna in 2017 used to address IRDs associated with the RPE65 gene.³

• The University of California-Davis received a $3.6 million grant for eye gene therapy research from the NEI.³The researchers are evaluating a less invasive way to inject gene therapy by injecting treatment into the suprachoroidal space, according to a press release issued in August 2025. The research will begin in non-human primates.
• BGTF-027 (Adverum Biotechnologies, licensed to Bluegen Therapeutics Foundation) is a gene therapy injected intravitreally to address blue cone monochromacy, a severe rare, inherited vision disorder linked to the X chromosome that occurs in boys. ³ BGTF-027 is an intravitreal gene therapy solution designed to deliver a functional copy of human L-opsin gene to the cone photoreceptors cells.⁴
• HORA-PDE6b (eyeDNA Therapeutics), delivers a full-length non-mutated copy of the functional human PDE6b gene into the subretinal space. It is being evaluated in a phase 1/2 trial for retinitis pigmentosa (RP). HORA-PDE6b has demonstrated clinically meaningful benefits in visual function and a good safety profile in patients with PDE6b at the 24-month follow-up from the ongoing phase 1/2 trial.⁵
• MCO-010 (Nanoscope Therapeutics) demonstrated durable 3-year clinically meaningful vision improvements in the REMAIN Study for treating RP. REMAIN results showed sustained, three-line visual gains vs baseline through 152 weeks for MCO-010 in patients having severe vision loss from RP, and a favorable safety profile,⁶ according to the company press release.
• OCU410ST (Ocugen) is a possible treatment of ABCA4-associated retinopathies, including Stargardt disease, an inherited macular degeneration. It uses an adeno-associated virus (AAV) delivery platform for the retinal delivery and is in a phase 2/3 trial. Ocugen and Kwangdong Pharmaceutical have entered a licensing agreement for OCU400, targeting RP in Korea. According to the company press release, OCU400 may be a one-time therapy for life to treat RP.⁷ In 2025, Ocugen announced a positive 2-year safety and efficacy update for the phase 1/2 OCU400 clinical trial to treat early to advanced RP in children and adults. According to the company, OCU400 demonstrated meaningful improvement, ie, a two-line gain (10 letters on the ETDRS chart), in low-luminance visual acuity in treated eyes when compared to untreated fellow eyes.⁷
• Encelto (revakinagene taroretcel-lwey, Neurotech Pharmaceuticals) was approved on March 5-6, 2025, to treat macular telangiectasia type 2, a rare neurodegenerative disease that causes irreversible vision loss. Encelto uses a small, semi-permeable capsule implanted in the eye that contains allogeneic retinal pigment epithelium cells genetically engineered to produce specific therapeutic proteins for targeted disease treatment.⁸
• VG801 (VeonGen Therapeutics, formerly ViGeneron) is a dual-AAV gene therapy developed to treat Stargardt disease. The therapy is under investigation in a phase 1/2 clinical trial. VG801 received FDA Rare Pediatric Disease Designation and is progressing in a first-in-human phase 1/2 trial for Stargardt disease, with functional endpoint development underway through the FDA’s Rare Disease Endpoint Advancementprogram.^9,10
• AAVB-039 (AAVantgarde Bio), an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Stargardt disease, has received orphan drug designation from the FDA and clearance of a clinical trial application (CTA) from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).¹¹ AAVB-039, which is currently being evaluated in the first-in-human, phase ½ CELESTE clinical trial (NCT07161544) in the US, is intended to deliver a functional copy of the disease-targeted ABCA4 gene. The gene therapy product uses a dual AAV vector, as ABCA4 is too large to be transported by a standard AAV vector. The therapy previously received FDA fast track designation in August 2025.¹¹
• SB-007 (SpliceBio), a protein splicing therapy, is being evaluated in the phase 1/2 ASTRA clinical trial for patients with Stargardt disease caused by the ABCA4 mutation. ASTRA is the first FDA-authorized clinical trial for a protein splicing therapy.¹²
• NPI-001 (Nacuity Pharmaceuticals, Inc.), an oral therapy for RP associated with Usher syndrome, achieved more than a 50% reduction in photoreceptor loss caused by RP associated with Usher syndrome over 2 years. NPI-001 was well tolerated, with no persistent drug-related adverse events, according to the company press release on September 11, 2025.¹³

AI and rare eye diseases

Artificial intelligence (AI) provides big plusses in the research into rare eye disorders by enhancing diagnostic accuracy in ophthalmology, which surpasses human capabilities in detecting conditions like glaucoma and diabetic retinopathy. In addition, personalized treatment strategies are optimized by AI, predicting patient responses and improving outcomes in conditions like age-related macular degeneration.¹⁴

AI currently is at the forefront of ophthalmologists’ minds. When asked about technologic advances in 2025, a recent survey found that ophthalmologists identified AI as by far the “most transformative trend in ophthalmology.”¹⁴ The survey found AI to be the clear frontrunner among available technologies, cited by 78% of respondents compared with the next cited trend, at a distance 11%, age-related macular degeneration/geographic atrophy treatments in the pipeline.

A study¹⁵ reported at the 2025 Association for Research in Vision and Ophthalmology annual meeting focused on the diagnosis of rare retinal diseases on fundus imaging because so few studies had undertaken that task.

The investigators conducted an observational case-control study to support the creation of a dataset of color fundus images to train and test an AI model. True color fundus imaging of the posterior pole was performed using a confocal fundus scanner. The AI model consisted of two deep neural networks.

The dataset including images obtained from 220 patients with RP, 101 with Stargardt disease, 162 healthy controls. The patients were divided into a was split in a training set of 196 RP cases, 77 Stargardt cases, 114 healthy controls to train the AI model and test set of 24 RP cases, 24 Stargardt cases, and 48 healthy controls). They reported, “The AI model achieved an overall accuracy of 97.9%. The sensitivity and specificity rates for RP sere 100% and 96%, respectively, and the sensitivity and specificity rates for STGD were 96% and 96%, respectively. Among the correctly classified RP patients, cases with small pigmentary changes were included, and among the correctly classified Stargardt patients, cases with mild macular degeneration were included.”

They concluded that the study introduced a robust and reliable AI model based on color fundus imaging that can significantly enhance the diagnostic process for rare retinal diseases, particularly, RP and Stargardt disease. Further research to develop more challenging classification tasks, eg, other rare retinal disease, and testing other devices, eg, handheld fundus camera, are being carried out by their group.

References

1. National Organization for Rare Disorders. Show your stripes for rare disease day with NORD. 2026; https://rarediseases.org/rare-disease-day/

2. Fighting Blindness Canada. Rare Disease Day: An update on inherited retinal disease research. 2025; published February 10. https://www.fightingblindness.ca/news/rare-disease-day-an-update-on-inherited-retinal-disease-research/

3. Myshko D. UC Davis receives $3.6 million grant for eye gene therapy research. Managed Healthcare Executive. 2025, August 15. https://www.managedhealthcareexecutive.com/view/uc-davis-receives-3-6-million-grant-for-eye-gene-therapy-research

4. Bluegen Therapeutics Foundation. https://bluegen.org/pipeline/#:~:text=BGTF%2D027%20is%20an%20intravitreal%20(IVT),to%20the%20cone%20photoreceptors%20cells

5. EyeDNA receives rare pediatric disease designation for gene therapy. Ophthalmology Management. December 17, 2024

6. Nanoscope Therapeutics announces durable 3-year vision improvements from REMAIN Study of MCO-010 in retinitis pigmentosa. 2025; October 22. https://www.prnewswire.com/news-releases/nanoscope-therapeutics-announces-durable-3-year-vision-improvements-from-remain-study-of-mco-010-in-retinitis-pigmentosa-302590734.html#:~:text=REMAIN%20results%20showed%20sustained%2C%203,profile%20maintained%20through%20three%20years.

7. Harp MD. Ocugen and Kwangdong complete licensing agreement for OCU400 gene therapy in Korea. Ophthalmology Times. 2025; September 15. https://www.ophthalmologytimes.com/view/ocugen-and-kwangdong-complete-licensing-agreement-for-ocu400-gene-therapy-in-korea

8. Flinn R. FDA Approves First-Ever Cell Therapy Treatment for Rare Progressive Eye Disease. Managed Healthcare Executive. March 20, 2025. https://www.managedhealthcareexecutive.com/view/fda-approves-first-ever-cell-therapy-treatment-for-rare-progressive-eye-disease

9. Young A. VG801 receives regenerative medicine advanced therapy designation for Stargardt disease. Ocular Surgery News. 2025, August 25. https://www.healio.com/news/ophthalmology/20250825/vg801-receives-regenerative-medicine-advanced-therapy-designation-for-stargardt-disease#:~:text=Key%20takeaways:,could%20potentially%20address%20unmet%20needs.

10. Gene therapy for Stargardt advances to trial. Retinal Physician. June 5, 2025. https://retinalphysician.com/news/2025/gene-therapy-for-stargardt-advances-to-trial/#:~:text=VeonGen%20announces%20new%20name%20and,and%20central%20nervous%20system%20diseases

11. Stansfield N. AAVantgarde’s Stargardt gene therapy AAVB-039 garners FDA orphan drug designation, cleared for trial in UK. CGTLive. October 21, 2025. https://www.cgtlive.com/view/aavantgarde-stargardt-gene-therapy-aavb-039-garners-fda-orphan-drug-designation-cleared-trial-uk#:~:text=October%2021%2C%202025-,AAVantgarde's%20Stargardt%20Gene%20Therapy%20AAVB%2D039%20Garners%20FDA%20Orphan%20Drug,products%20Regulatory%20Agency%20(MHRA).

12. Stargardt disease research advances. Foundation Fighting Blindness. 2025, October 24. Fightingblindness.org/news/stargardt-disease-research-advances-862#:~:text=SpliceBio%2C%20a%20genetic%20medicines%20company,for%20a%20protein%20splicing%20therapy.

13. Nacuity Pharmaceuticals announces positive data from clinical trial evaluating NPI-001to treat retinitis pigmentosa associated with Usher syndrome. September 11, 2025. https://www.nacuity.com/news/nacuity-pharmaceuticals-announces-positive-data-from-clinical-trial-evaluating-npi-001-to-treat-retinitis-pigmentosa-associated-with-usher-syndrome/#:~:text=Nacuity%20Pharmaceuticals%20Announces%20Positive%20Data,plan%20to%20initiate%20in%202026.

14. Charters L. How AI is reshaping ophthalmology in 2025 and beyond. Ophthalmology Times. Published June 2025. https://www.ophthalmologytimes.com/view/how-ai-is-reshaping-ophthalmology-in-2025-and-beyond#:~:text=Some%20key%20developments%20include%20the,the%20forefront%20of%20ophthalmologists'%20minds.

15. Boccia R, Pagnano ME, Melillo P, et al. Artificial intelligence to support diagnosis of rare retinal diseases based on fundus imaging. Invest Ophthalmol Vis Sci. 2025;66:5443