Thomas A. Ciulla, M.D.

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...

10/30/2025

Presenting at the Real-World Data Ophthalmology Summit. https://realworlddatasummit.com/

I have published real-world data analyses demonstrating high unmet need in common causes of vision loss, including , and . I am currently working with a company to develop a dual-pathway for that builds on complement pathways and adds neuroprotection, targeting functional benefit.

"The Real World Data in Ophthalmology Summit addresses the methodology of real-world studies, highlight sources for these studies to be completed, and to demonstrate best practices that both researchers, physicians, and pharmaceutical companies can achieve."

09/25/2025

In the current issue, Thomas A. Ciulla, MD, reviews how suprachoroidal injections provide a targeted route for various therapies. Read more: https://ow.ly/gglJ50WYHn8

09/23/2025

Honored to speak at the 6th Gene Therapy for Ophthalmic Disorders Summit this December in Raleigh, NC:

I will present "Developing Dual-Acting Gene Therapy to Combat Geographic Atrophy & Prevent AMD Progression", sharing research on a first-in-class bicistronic platform.

This is a novel approach combining neuroprotection and complement modulation to address the significant unmet need in , with potential gene-agnostic extension to . This dual-pathway strategy offers potential advantages over current single-target therapies.

This summit brings together the leading voices working to restore vision through genetic medicine, from regulatory strategy to clinical translation.

Looking forward to sharing our learnings and connecting with fellow innovators advancing this transformative field.

Check out the full agenda: https://lnkd.in/gWw-tMdv

09/18/2025

Excited to share this latest publication reviewing the remarkable evolution of suprachoroidal in this month’s Retinal Physician.

As one who helped develop ® - the first FDA-approved therapy - & other suprachoroidal therapies in clinical trials, it is gratifying to see how this innovative approach has catalyzed an entire platform of promising new treatments.

What began as a novel concept for delivering medications to the has blossomed into multiple clinical programs targeting major causes of loss.

The suprachoroidal space is now being investigated for:
—Next-generation for
—Plasma Kallikrein Inhibitor for macular edema
— for &
—Virus-like drug conjugates for choroidal melanoma

This global adoption & continued reaffirms that persistence & scientific collaboration can open entirely new therapeutic frontiers. Most importantly, this technology is helping patients across continents, validating years of R & D that made suprachoroidal delivery a clinical reality.

Grateful to all researchers, clinicians & industry partners who have helped advance this field. The future of ocular drug delivery looks brighter than ever!

Clinical data support this targeted route for small molecules, gene therapy, and oncologic agents, with a good safety profile and potential to reduce treatment burden.