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John Kitchens, MD, and Scott Krzywonos take stock of the biggest retina data readouts of 2026 — from a superiority study from Ocular Therapeutix to a Kodiak comeback and a gene therapy from Beacon that could be the first approval for an inherited retinal disease since Luxturna in 2017. Also discussed: topline data for remigromig (Merck/EyeBio) and Duravyu (EyePoint).

The conversation covers what each dataset means in clinical terms, which presentations at AAO are must-attends, and what happens when all these new mechanisms — TKIs, ABC polymers, Wnt pathway agonists, IL-6 inhibitors, and gene therapy — arrive in clinic around the same time.

The episode closes with a broader question: are we entering an era of retina that looks more like oncology, where doctors match individual patients to specific treatments rather than relying on trial and error?

Hosts: John Kitchens, MD, Scott Krzywonos

Topics Covered

Axpaxli / SOL-1 (Ocular Therapeutix)

A superiority study — rare in retina. Primary endpoint at month 9: Axpaxli patients maintained vision at a significantly higher rate than those treated with a single injection of aflibercept.

Study design selected for highly responsive patients, which may have produced a stronger-than-expected control arm response. More than half of aflibercept control patients went six months before needing rescue treatment.

Axpaxli holds a Special Protocol Assessment from the FDA, which should support a cleaner approval pathway. NDA filing planned for 2026.

Darius M. Moshfeghi, MD, presents SOL-1 results at AAO Subspecialty Day, Friday, October 9, 4:35 PM.

Duravyu / LUGANO (EyePoint Pharmaceuticals)

Phase 3 non-inferiority study for wet AMD. Nine patients in the treatment arm drove the primary endpoint miss.

The LUCIA companion study remains the decisive dataset; if positive, expect an NDA submission in 1H 2027.

Carl D. Regillo, MD, FACS, presents LUGANO results at AAO Subspecialty Day, Friday, October 9, 4:30 PM.

Zenkuda / DAYBREAK (Kodiak Sciences)

Phase 3 wet AMD study; three arms — Zenkuda (four monthly loading doses, then PRN with zero-fluid-tolerance AI retreatment criteria), tabirafusp-ted (four monthly loading doses, then every-other-month proactively), and aflibercept (three monthly loading doses, then every eight weeks).

Zenkuda: 7.2-letter vision gain vs. 7.6 for aflibercept. 54% of patients reached 6-month dosing at year 1 under strict treat-to-dryness criteria. 0% intraocular inflammation.

The key modification from KSI-301: Zenkuda includes 20% free drug for immediate drying effect, with 80% ABC-conjugated drug providing the approximately 20-day half-life and durability.

Tabirafusp-ted also met its primary endpoint, but added no additional vision gains vs. aflibercept. IL-6 inhibition may have a stronger case in DME and uveitic macular edema; ALTO Phase 3 in DME is actively enrolling. Kodiak plans a Q4 2026 three-indication BLA for Zenkuda (wet AMD, diabetic retinopathy, RVO).

Charles C. Wykoff, MD, PhD, presents DAYBREAK results at AAO Subspecialty Day, Friday, October 9, 4:40 PM.

Remigromig / BRUNELLO (Merck)

Phase 2b/3 non-inferiority study for DME. Both doses (0.5 mg and 0.8 mg) demonstrated non-inferiority to monthly ranibizumab 0.5 mg at week 52.

A Wnt pathway agonist — not an anti-VEGF. Targets endothelial cell tight junctions in the retinal vasculature. Higher rates of PDR and vitreous hemorrhage in the remigromig arms vs. control; full data not yet seen beyond the press release.

John’s read: likely an add-on to anti-VEGF, not a replacement. Anti-VEGF co-therapy should mitigate the proliferative signal. Target population: the roughly 40% of DME patients with persistent edema despite treatment (per DRCR Protocol I and Protocol T). Monthly dosing is a practical disadvantage vs. Ozurdex; absence of cataract and IOP risk is the advantage. BAROLO companion study expected Q1–Q2 2027.

Donald J. D’Amico, MD, presents BRUNELLO results at AAO Subspecialty Day, Saturday, October 10, 5:10 PM.

Laru-zova / VISTA (Beacon Therapeutics)

Pivotal Phase 3 gene therapy for X-linked retinitis pigmentosa — the first XLRP trial to meet its primary endpoint, and the first potential gene therapy approval in retina since Luxturna in 2017.

Primary endpoint: low luminance visual acuity responder rate (gain of 15+ letters at month 12). High-dose arm: 31%. Low-dose arm: 24%. Untreated control: 0%.

XLRP is more prevalent than RPE65-mediated LCA and has a characteristic inheritance pattern that may make family-based identification more tractable. Enrollment required VA of 20/32 or better — earlier diagnosis and genetic testing are prerequisites for treatment.

Robert A. Sisk, MD, FACS, FASRS, presents VISTA first-time results at AAO Subspecialty Day, Saturday, October 10, 4:13 PM.

The Bigger Picture: Precision Retina?

The arrival of multiple new mechanisms in close succession raises a question Charles C. Wykoff, MD, PhD, floated on the Kodiak investor call: is retina approaching an oncology-style era where specific patients are matched to specific treatments?

John’s view: we’re not there yet. The DRCR Retina Network is well-positioned to run the head-to-head comparison studies that would generate that evidence. AI may eventually help identify disease phenotypes that predict response to one mechanism vs. another — but the data to train it on don’t exist yet.

Key Takeaways

Five major Phase 3 datasets in one year — SOL-1, LUGANO, DAYBREAK, BRUNELLO, and VISTA — each with different mechanisms, endpoints, and implications. Friday and Saturday afternoon at AAO Subspecialty Day are the sessions to be in the room for.

TKIs and Zenkuda are both targeting durability in wet AMD but via different mechanisms; real-world data will tell us whether the trial results hold outside controlled conditions.

Remigromig’s safety signal in BRUNELLO will be the central topic at Dr. Don D’Amico’s Saturday talk; the full data, not just the press release, will determine how seriously practices take the PDR risk.

VISTA represents a potential turning point for inherited retinal disease — and a reminder that the stakes in retina extend well beyond market dynamics.

John Kitchens, MD, and Scott Krzywonos break down the AAO 2026 annual meeting in New Orleans (October 9–12) — whether it still matters, what to catch at Subspecialty Day, and which late-breaking Phase 3 data presentations could move the field. Each host shares their top four talks, and the Vitreoretinal View covers the surgical program.

A quick correction from the prior episode: the SOL-1 primary endpoint was at month 9, not month 6, as stated in our previous episode. Corrections welcome at info@retinup.com.

Hosts: John Kitchens, MD, Scott Krzywonos

Topics Covered

AAO 2026: Does It Still Matter?

In-person attendance may be down post-COVID, but virtual access has expanded the meeting's reach significantly. Still a premier venue for late-breaking Phase 3 data and surgical education. New Orleans in October doesn't hurt.

John is on the podium in two places: the 2026 Debate Session (Friday, 2:45 PM — No Flap for Macular Hole) and a vitrectomy for floaters talk at Refractive Subspecialty Day. Plus, John pays tribute to Kirk Packo, MD — the legendary AAO debater — and his famous 2006 New Orleans talk calling out industry over Avastin access.

John's Top Four Talks

No. 4 — Friday, 5:10 PM: Ehsan Rahimy, MD, presents 36-month safety data from the PRIMA photovoltaic retinal implant trial in geographic atrophy. A European device that has hit mainstream news; risk of accelerating atrophy and debate over whether VA gains reflect true restoration or magnification make this one to watch.

No. 3 — Friday, 5:05 PM: Raj K. Maturi, MD, presents 12-month topline results from the Phase 2 ArMaDa trial of OCU-410, a modifier gene therapy for GA. Back-to-back with PRIMA; gene therapy for GA is the right target given the need for sustained delivery.

No. 2 — Saturday, 4:56 PM: Arshad M. Khanani, MD, MA, presents Phase 2 ELAAVATE data for RGX-314 (Regenxbio), a subretinal gene therapy for center-involved DME. Subretinal and suprachoroidal delivery routes both in development; data could signal what gene therapy for DME looks like before the Phase 3 wave hits.

No. 1 — Saturday, 5:10 PM: Donald J. D'Amico, MD, presents the BRUNELLO pivotal trial results for Remigromig (MK-3000, Merck) in DME — a Wnt pathway inhibitor that targets endothelial cell tight junctions rather than VEGF. A genuinely new mechanism; if it wins on VA and drying, it could be additive to anti-VEGF. Monthly ranibizumab as the comparator is defensible given the ride/rise data and Protocol T all-comers results. Merck's second program, tuspetinib (Tie2 activator, ANG1 pathway), is next up in the pipeline.

Scott's Top Four Talks

No. 4 — Friday, 8:30 AM: Jason Hsu, MD (Wills Eye Hospital), Top Journal Articles That Influenced My Practice. Not a single dataset — a real-world appraisal of what actually breaks through into practice.

No. 3 — Saturday, 4:37 PM: Nisha Acharya, MD, presents week 52 MEERKAT and SANDCAT data for vamikibart in uveitic macular edema. Week 16 data were presented at AAO 2025 and ARVO 2026; the 1-year read will be more definitive. Interesting wrinkle: higher dose won in MEERKAT, lower dose in SANDCAT.

No. 2 — Friday, 4:40 PM: Charles C. Wykoff, MD, PhD, presents the DAYBREAK Phase 3 trial for Kodiak Sciences — a three-arm study comparing KSI-301 (ABC anti-VEGF), KSI-501 (ABC anti-VEGF + anti-IL-6), and aflibercept. First time (we think) a sponsor has run two of their own candidates head-to-head against a control.

No. 1 — Saturday, 4:13 PM: Robert A. Sisk, MD, presents first-time pivotal VISTA trial results for laru-zova gene therapy (Beacon Therapeutics) for X-linked RP. Could be the second gene therapy approved in retina, and the first since Spark in 2017. Larger treatable population than RPE65-mediated LCA; safety around subretinal delivery in a pigmented retina will be key.

Vitreoretinal View: Surgical Talks at Subspecialty Day

Friday, 8:16 AM — Ninel Z. Gregori, MD: Subretinal administration of photoreceptor precursor cells in RP (Surgical Videos: Cool Cases and Complications). Subretinal photoreceptor delivery is distinct from gene therapy; anatomic and functional outcomes to watch.

Friday, 11:04 AM — Aleksandra V. Rachitskaya, MD: When to Worry and When Not to Worry About Retinoschisis. Schisis-related detachments are technically demanding with high PVR risk; looking for pearls on when to operate, laser options, tamponade choice.

Friday, 11:11 AM — Colin A. McCannel, MD: A Decade of 27-Gauge Vitrectomy Surgery. Less than 5% of US surgeons use 27-gauge; Alcon Unity system is optimizing flow and stiffness. Does 25-gauge still do everything 27 can without the compromises?

Saturday, 3:45 PM — Omesh P. Gupta, MD: Gore-Tex Scleral-Fixated IOL Technique (How Do I Do It).

Saturday, 3:52 PM — Murtaza K. Adam, MD: Yamane Technique IOL Placement (How Do I Do It).

Saturday, 4:06 PM — Glenn C. Yiu, MD, PhD: Suprachoroidal Injection Tips and Tricks. Increasingly relevant as suprachoroidal gene therapy delivery (RGX-314) advances and approved suprachoroidal steroid delivery matures.

Key Takeaways

AAO 2026 features an unusually dense late-breaking data slate: BRUNELLO, DAYBREAK, VISTA, MEERKAT/SANDCAT, PRIMA, and ArMaDa all read out at the same meeting.

BRUNELLO is the most mechanistically novel: a Wnt pathway inhibitor for DME that could eventually combine with anti-VEGF. VISTA is the most consequential for the inherited retinal disease field if positive.

Suprachoroidal delivery and 27-gauge vitrectomy are two surgical trends worth watching across multiple talks.

Correction: the SOL-1 primary endpoint was at month 9, not month 6, as stated on our previous episode.

Sponsors

This episode is made possible by Genentech, maker of Vabysmo (faricimab-svoa). Hear peer perspectives and case studies in the Purple Chair series, including Dr. David A. Eichenbaum on a real-world DME patient, at Vabysmo-HCP.com.

This episode is brought to you by Alcon, a global leader in eye care, including Unity VCS. Learn more at unityvcs.com.

Credits
Production & Marketing: Laura Brown | Business Operations: Liz Hogan

🎧 Listen at RetinUp.com | Apple Podcasts | Spotify | YouTube

John Kitchens, MD, and Scott Krzywonos take stock of the three biggest retina news stories of 2026 — the SOL-1 superiority data for Axpaxli (Ocular Therapeutix), the FDA approval of Lytenava (Outlook Therapeutics), and the LUGANO Phase 3 (near) miss for Duravyu (EyePoint Pharmaceuticals) — and look ahead to three imminent late-phase readouts that could reshape the field before year's end: DAYBREAK for Zenkuda (Kodiak), BRUNELLO for Restoret (Merck/EyeBio), and ARCHER 2 for vonaprument (Annexon). 

Carl J. Danzig, MD, then joins for a candid conversation about leaving a solo retina practice after 14 years, navigating a non-compete, commuting across Alligator Alley, and what it actually costs — personally and professionally — to make a major mid-career professional transition. He recently joined Fort Lauderdale Eye Institute as one of four retina specialists, beginning to see patients there on August 24, 2026. 

Hosts: John Kitchens, MD, Scott Krzywonos

Topics Covered

2026 Pipeline Check-In: Catching Our Breath 

Axpaxli / SOL-1 (Ocular Therapeutix): first superiority study in retina; at week 36, 74% of Axpaxli patients maintained vision vs. 56% on a single aflibercept injection; at 1 year, 66% of Axpaxli patients had not lost 10 letters; NDA filing planned for 2026.

Lytenava (Outlook Therapeutics): FDA-approved July 2026 for wet AMD — the first FDA-approved ophthalmic formulation of bevacizumab; measured commercial rollout planned for Q4 2026; full commercialization early 2027. Key unresolved question: impact on compounded bevacizumab access, particularly for non-wet AMD indications including DME, CRVO, BRVO, and myopic CNV.

Duravyu / LUGANO (EyePoint Therapeutics): primary non-inferiority endpoint missed in the full dataset; attributed to nine outlier patients in the treatment arm with vision loss unrelated to wet AMD; ad hoc analysis excluding those patients showed non-inferiority; LUCIA companion study topline data expected Q4 2026.

2026 Pipeline Check-In: What's Coming

Kodiak Sciences — DAYBREAK (Zenkuda / KSI-501): Phase 3 non-inferiority study for wet AMD; two investigational arms vs. aflibercept; topline data expected September 2026. Kodiak's prior KSI-301 missed its primary endpoint; lessons learned informed DAYBREAK's design.

Merck — BRUNELLO (Restoret / MK-3000): Wnt pathway agonist antibody acquired via EyeBio; Phase 3 non-inferiority trial for DME; data expected within 4 to 6 weeks of recording; a second Merck program — an ang-1 upregulator and VEGF inhibitor designed to activate the Tie2 receptor rather than merely inhibiting ang-2 — follows behind.

Annexon — ARCHER 2 (vanoprument / ANX007): C1q complement inhibitor for GA; distinct mechanism from C3 (pegcetacoplan) and C5 (avacincaptad pegol) inhibitors; Phase 2 showed a visual acuity benefit without slowing lesion growth; hypothesis: C1q inhibition protects photoreceptors upstream of RPE loss, with atrophy reduction expected to emerge over 12–24 months; Phase 3 primary endpoint is vision preservation, not lesion growth.

Carl J. Danzig, MD, on Switching Practices at Mid-Career

Background: Temple University medical school, Wills Eye tumor research, residency at Charles Drew (transferred to SUNY Downstate after program closure), fellowship at UT Southwestern; joined Rand Eye Institute as the practice's first and only retina specialist in 2012.

Solo practice realities: PI on 59 clinical trials as a solo retina specialist in an anterior segment practice; required extensive coverage arrangements and leveraged a full network of South Florida retina colleagues; elected to Retina Society.

Why he left: felt like "salmon swimming against the current" in an anterior segment culture; outgrowing his role; needed partners, shared call, and a practice aligned with his research identity and professional goals.

The transition year: geographic restriction meant commuting from Fort Lauderdale to Bonita Springs (Advanced Retina Institute) — across Alligator Alley — Tuesday through Thursday most weeks; often away five to six nights at a time including commercial speaking and international meetings.

The real costs: income went to zero during the gap; anxiety about the non-compete timeline; mental load of solo parenting for his wife; being a diminished version of himself at home after long stretches away. "Phil Rosenfeld, MD, told me I jumped out of an airplane holding my family's hand and no one had a parachute."

Fort Lauderdale Eye Institute: one of four retina specialists; seven minutes from home; active clinical trial program; practice aligned with his values. First patient day: August 24, 2026.

Advice to anyone considering a mid-career move: know your worth, don't undervalue yourself, move sooner rather than later if the fit is wrong, and build your network before you need it.

Key Takeaways

The three biggest retina stories of 2026 — SOL-1, Lytenava, and LUGANO — set up a fall season with multiple Phase 3 readouts that could further reshape the treatment landscape.

Annexon's ARCHER 2 is the most mechanistically distinct GA program in Phase 3 — a C1q inhibitor targeting photoreceptors upstream of RPE loss. 

Leaving a practice at mid-career is a financial, legal, logistical, and deeply personal decision — Carl Danzig's year-long transition is a useful blueprint for anyone considering it.

Network-building early in training is the single most durable investment a retina specialist can make.

Sponsors

This episode is made possible by Genentech, maker of Vabysmo (faricimab-svoa). Hear peer perspectives and case studies in the Purple Chair series at Vabysmo-HCP.com.

This episode is brought to you by Ocular Therapeutix, a biopharmaceutical company working to redefine the retina experience across drug development, treatment, and outcomes. Learn more at OCUTX.com.

Credits
Production & Marketing: Laura Brown | Business Operations: Liz Hogan

🎧 Listen at RetinUp.com | Apple Podcasts | Spotify | YouTube