Thomas A. Ciulla, M.D.

07/02/2026

A newly published review on an area of research that may matter to anyone living with wet age-related macular degeneration.

For the past two decades, the standard treatment for wet AMD has been anti-VEGF injections into the eye. They work well, but they have to be repeated, often for years, and keeping up with the visits is hard for many patients. Missed treatments can mean lost vision.

Researchers are now studying gene therapy as a possible alternative: a single treatment that may reduce, or one day remove, the need for repeated injections. Several of these therapies are in late-stage clinical trials. They are not yet approved or available, and important questions about long-term safety and durability are still being studied. But the progress is real, and it is worth understanding.

The review looks at where this research stands today. It is written for physicians and scientists, though patients who want a look at what may lie ahead are welcome to read it.

If you or a loved one is being treated for macular degeneration, the most important step remains the same: keep your appointments and stay in close contact with your retina specialist. Please bring any questions about new or future treatments to your own eye doctor, who knows your case.

Retina Specialist focuses on the latest advances in the diagnosis, medical management and surgical treatment of diseases of the retina, along with practical, real-world advice from leading clinicians and other experts on managing the successful retina practice.

06/04/2026

Proud to share our new paper in Med by Cell Press, the high impact flagship medicine journal from the publisher of Cell: https://authors.elsevier.com/a/1nDDm9UKeTtQIA
"Gene therapy and cost-effectiveness analysis: Current issues and future research.

GeneTherapy is changing what is possible in medicine. A single treatment can correct the root cause of a disease that once meant a lifetime of treatments and slow, managed decline. For patients and families, that is not an incremental gain. It can be the difference between losing independence and keeping it, between losing sight and holding onto it.

The problem is that our tools for measuring value were built for chronic, pay-as-you-go medicine. When all of the cost arrives upfront and the benefit unfolds over decades, standard cost-effectiveness analysis can understate what these therapies are worth to patients and to society. Our review maps where current methods fall short and where the field is heading: outcomes-based payment, value frameworks that look beyond the traditional QALY, and better ways to model long-term durability.

This is not an academic exercise. How we choose to value one-time therapies will decide which ones reach patients at all.

The science is arriving. The economics need to keep pace.

05/17/2026

Numerous presentations, including this one on gene therapy for AMD/macular degeneration, during two weeks at ARVO (Denver) + American Society of Gene & Cell Therapy (Boston).

04/23/2026

Pleased to share our newly published review in Genes: "Gene-Agnostic Therapeutic Strategies for Inherited Retinal Diseases: Neuroprotection and Immunomodulation." https://www.mdpi.com/2073-4425/17/4/392

More than 280 genes cause inherited retinal disease, making a gene-by-gene therapeutic approach impractical. Luxturna's landmark approval validated AAV-based gene replacement for biallelic RPE65-mediated disease, but the vast majority remain without approved options.

This review examines gene-agnostic strategies that target common downstream pathways across IRD genotypes. Neuroprotection, via neurotrophic factors such as PEDF, CNTF, RdCVF, BDNF, FGFs, GDNF, and proinsulin, has demonstrated photoreceptor preservation across multiple preclinical models regardless of the underlying mutation.

Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxtur...

03/31/2026

Since its publication, our manuscript "Gene Therapy for Non-Hereditary Retinal Disease: Age-Related Macular Degeneration, Diabetic Retinopathy, and Beyond" has been cited 30 times and viewed by 11,495 readers...

Gene therapy holds promise as a transformative approach in the treatment landscape of age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), aiming to address the challenges of frequent intravitreal anti-vascular endothelial growth factor (VEGF) injectio...

03/11/2026

🧬 Could dual-pathway gene therapy transform geographic atrophy treatment?

Thomas A. Ciulla, MD, MBA explores a strategy combining neuroprotection and complement modulation to address multiple GA disease mechanisms.

👉 Read: https://ow.ly/Iag650Yp5QE

03/02/2026

Pleased to share my article in the March/April issue of Retinal Physician: "Dual-Pathway Gene Therapy for Geographic Atrophy."

Geographic atrophy is the advanced stage of dry age-related macular degeneration, affecting approximately 5 million people worldwide and causing progressive, irreversible vision loss. While the recent approval of complement inhibitors was an important step, these treatments offer modest benefits with significant treatment burden. Notably, the European Medicines Agency refused marketing authorization for one agent and rendered an unfavorable opinion on the other, citing a lack of meaningful improvement in vision or everyday functioning.

In this article, I discuss the rationale for a new approach: combining neuroprotection and complement modulation through gene therapy. Rather than targeting a single pathway, this strategy restores two naturally occurring protective proteins that become depleted as the disease progresses — potentially offering greater benefit from a single treatment.

Some key developments in this space:
—The FDA's approval of Encelto in 2025 validated neuroprotection as an approvable approach for macular degenerative disease, a meaningful milestone for the field
—Preclinical research shows that combining neuroprotective and anti-inflammatory mechanisms produces synergistic effects beyond what either achieves alone
—Gene therapy delivery may overcome the limitations of proteins with very short half-lives that make repeated injections impractical

As a retina specialist, I find this an exciting time in our field. The science is advancing rapidly, and I'm grateful to be involved in research aimed at developing better options for patients with geographic atrophy and other retinal degenerative diseases.

https://res.cloudinary.com/broadcastmed/image/fetch/e_unsharp_mask:70,q_auto,c_fill,f_auto,w_170,h_230/dpr_auto/https://retinalphysician.com/media/4tbpmbe0/010926-omd-web-covers-staff.jpg

01/22/2026

Deeply grateful to receive the 2026 Castle Connolly Top Doctor recognition, now 15 consecutive years. This distinction, awarded to just 7% of U.S. physicians annually, reflects the trust and support of my peers in the medical community. It fuels my ongoing commitment to advancing healthcare, medical research, and new therapies for unmet need.

https://www.castleconnolly.com/top-doctors/thomas-ciulla-ophthalmology-108cc001280

11/19/2025

Thomas A. Ciulla, MD, MBA, discusses best practices for clinical research site collaboration. Read more: https://ow.ly/F6b850XpU6y

11/11/2025

Honored to share insights on clinical research excellence in this month's Retinal Physician, drawing from my experience as both a clinical investigator and biotech executive.

After reviewing FDA warning letters, including three issued to ophthalmologists, clear patterns emerge that every clinical research site should understand:
—Protocol adherence requires personal supervision of critical decisions
—IND requirements remain a knowledge gap in ophthalmology, particularly for combination products
—Informed consent in retinal research demands special attention given vision loss's emotional impact
—Data integrity and contemporaneous documentation are non-negotiable
—Quality consistently trumps quantity in site-sponsor relationships

The commitments in FDA Form 1572 are not bureaucratic obstacles—they are patient safety imperatives that define us as clinical investigators.

Having worked on FDA approved therapies, including , , and , I have witnessed how rigorous site practices accelerate therapeutic development. The most successful sites build systematic approaches spanning multiple studies over years.

As we advance transformative therapies—from for inherited retinal diseases to novel delivery systems for and —our research practices must be worthy of patient trust.

Excellence in clinical research is a choice we make with every study.

An examination of 12 randomly selected FDA warning letters, including 3 directed at ophthalmologists, serves as a sobering reminder of what happens when investigators fail to uphold these standards. The commitments in Form 1572 are not burdens imposed by regulatory bureaucracy—they are professiona...