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Three days after EyePoint Pharmaceuticals released topline LUGANO Phase 3 data, Jay S. Duker, MD, President & CEO, joins John Kitchens, MD, and Scott Krzywonos to break down what the results actually mean.
Three days after EyePoint Pharmaceuticals released LUGANO Phase 3 topline data, Jay S. Duker, MD, President & CEO, joins John Kitchens, MD, and Scott Krzywonos to explain what actually happened. Duravyu (vorolanib, Durasert E sustained-release insert) missed its primary non-inferiority endpoint in the full dataset — driven by nine patients in the treatment arm who lost 15+ letters for reasons unrelated to wet AMD control. Dr. Duker walks through the mechanism, the outlier analysis, and why he remains optimistic heading into LUCIA.
The Vitreoretinal View features Miles Harper, independent ophthalmology consultant, who uses two case studies — the collapse of Bionics' VR surgical headset and the slow adoption of heads-up 3D visualization — to examine why promising OR technologies fail to reach commercial success. The conversation closes with a grounded look at where AI and robotics are actually headed in the surgical suite.
Hosts: John Kitchens, MD, Scott Krzywonos
Topics Covered
Jay S. Duker, MD, on the LUGANO Data
Duravyu mechanism: small molecule TKI with pan-VEGF receptor activity (intracellular), plus PDGF (antifibrotic) and JAK1 (anti-inflammatory via IL-6) activity; delivered as a 2.7 mg bioerodible intravitreal insert every six months; systemic absorption at picogram levels only.
Study design: randomized, double-masked non-inferiority trial; aflibercept 2mg loading phase for all patients; 75% treatment-naive, 25% previously treated — the first wet AMD Phase 3 to enroll previously treated patients; primary endpoint averaged BCVA change at weeks 52 and 56.
Primary endpoint miss: control arm lost only 0.5% of patients to 15+ letter vision loss vs. historical ~4% for aflibercept 2mg — an unexpectedly strong comparator performance. Nine Duravyu patients lost 15+ letters for non-AMD reasons: six due to GA, two due to glaucoma, one due to repaired retinal detachment with resulting cataract.
Re-randomization analysis: CMO Ramiro Ribeiro, MD, PhD, re-randomized all 15+ letter losers across both arms ten times; every simulation produced non-inferiority with a mean letter difference of -1.3 to -2.0 — well within the margin.
Secondary data: 42% reduction in treatment burden vs. aflibercept (~2 fewer injections/year); 76% supplement-free at week 32; 54% supplement-free at week 56; four-micron OCT difference vs. control; supplement-free subgroup alone was non-inferior with a three-micron OCT difference.
GA data: Duravyu arm showed lower GA rates at end of trial (24%) vs. aflibercept arm (29%); no evidence drug causes or accelerates GA.
Regulatory path: LUCIA topline data expected Q4 2026; NDA submission planned 1H 2027 if positive. Precedents for one missed/one positive Phase 3 in retina: pegcetacoplan (DERBY/OAKS) and Lytenava.
Vitreoretinal View: OR Technology, Adoption & AI (Miles Harper)
Bionics case study: Israeli company developed a VR surgical headset with gesture-based controls — too disruptive to workflow, unclear value proposition vs. the analog microscope, and priced beyond what the marginal benefit could justify. First-mover disadvantage: arrived before the use case was fully defined.
Heads-up 3D visualization: similar adoption ceiling — compelling technology, real ergonomic benefits, but incremental rather than transformative improvement over the standard microscope; declining surgical reimbursements raise the break-even bar for surgical centers. Multiple entrants (Alcon, Zeiss, Heidelberg, Bausch, others) will drive prices down; generational familiarity with screens will drive adoption up.
AI and robotics: autonomous robotic surgery is coming — already deployed outside ophthalmology — but surgeon oversight will remain essential. Near-term AI value in the OR: image reading, fluid monitoring, cell counting, vitreous sensing — marginal, non-intrusive efficiencies that integrate without disrupting workflow. Contrast with AI as Skynet: the most useful applications will feel like spell check, not science fiction.
Key Takeaways
LUGANO missed its primary endpoint, but the secondary data and re-randomization analysis give EyePoint a credible argument that nine atypical patients — not drug failure — drove the results.
A positive LUCIA trial may be sufficient for NDA approval; precedent in retina for one missed and one positive Phase 3 exists.
OR technology adoption fails when it disrupts workflow without sufficient value exchange — the lesson from Bionics applies equally to heads-up 3D and will apply to AI and robotics.
The near-term AI opportunity in the OR is incremental efficiency, not autonomy.
Sponsors
This episode is made possible by Genentech, maker of Vabysmo (faricimab-svoa). Hear peer perspectives and case studies — including Dr. David A. Eichenbaum, MD, unpacking what drying looked like in a real-world DME patient — in the Purple Chair series at Vabysmo-HCP.com.
This episode is brought to you by Alcon, a global leader in eye care with an industry-leading breadth of surgical products and solutions, 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
Breaking news: EyePoint Pharmaceuticals announced LUGANO Phase 3 topline data this morning. Duravyu, an investigational sustained-release TKI for wet AMD, did not meet its primary non-inferiority endpoint in the full dataset — confounded by nine patients in what EyePoint is calling an asymmetric cohort. John Kitchens, MD, and Scott Krzywonos break down what it means, what comes next, and why TKIs still win as a class.
Breaking news: EyePoint Pharmaceuticals announced topline data from LUGANO, the first of two pivotal Phase 3 trials evaluating Duravyu (vorolanib) for wet AMD, on the morning of August 17, 2026.
The primary non-inferiority endpoint was not met in the full dataset. EyePoint attributes this to an asymmetric cohort of nine patients in the treatment arm whose outcomes significantly skewed the results. In an unplanned ad hoc analysis excluding those nine patients, Duravyu was non-inferior to aflibercept 2 mg. Safety was clean, treatment-free intervals were compelling, and the companion LUCIA study remains on track for Q4 2026 topline data.
John Kitchens, MD, and Scott Krzywonos recorded this episode before the market opened to break down the study design, the ad hoc analysis question, and what the FDA is likely to do with these data. Plus, they examine why TKIs as a class — and some other companies — may be the real winners from this morning's news.
Hosts: John Kitchens, MD, Scott Krzywonos
Topics Covered
LUGANO Topline Data: What Happened
Study design: randomized, double-masked, non-inferiority trial; Duravyu 2.7 mg every six months vs. aflibercept 2 mg every other month (EOM); 211 patients in the treatment arm; a significant percentage of patients were previously treated — an unusual and real-world-reflective design feature; primary endpoint assessed at weeks 52 and 56.
Primary endpoint: not met in the full dataset; control arm performed exceptionally well — no patients lost three or more lines of vision in the first six months, compared to approximately 5% in historical wet AMD Phase 3 comparators.
The asymmetric cohort: nine patients in the treatment arm drove the primary endpoint miss; EyePoint characterizes these as an atypical subgroup. In an unplanned ad hoc analysis excluding these nine patients, Duravyu was non-inferior to the control arm.
Ad hoc analysis: not a pre-specified endpoint; FDA may consider it but likely will not base approval on it alone. The key question is whether LUCIA — the companion trial — delivers a clean positive result. John's view: LUCIA will need to be positive for any approval pathway; the FDA has approved products on one pivotal trial before (e.g., pegcetacoplan in DERBY/OAKS), so a strong LUCIA result may be sufficient.
Treatment-free intervals: approximately 42% reduction in treatment burden vs. aflibercept; roughly consistent with data from SOL-1 — validating the TKI mechanism as durable. At week 32, 76% of
Duravyu patients were supplement free.
Safety: clean; no ocular inflammation, vasculitis, or unexpected safety signals; consistent with prior TKI studies and anti-VEGF experience.
What It Means for the Field
TKIs win as a class: treatment-free interval data confirm durability and mechanism; the question is not whether TKIs work but how they will be positioned alongside next-generation anti-VEGFs.
Second-generation anti-VEGFs as potential beneficiaries: aflibercept 8 mg and faricimab approximate extended intervals with approved labeling; a delayed or complicated TKI approval pathway could strengthen their near-term positioning.
Study design implications: John raises the question of whether future TKI trials will exclude patients with geographic atrophy or other confounders; enrollment criteria may tighten, potentially slowing trial timelines.
AI and enrollment: Scott raises the possibility that AI-assisted health record analysis could better identify appropriate candidates in real time — particularly relevant as trials increasingly enroll previously treated patients.
What's Next
LUCIA topline data: expected Q4 2026; if positive, EyePoint plans NDA submission in 1H 2027.
Upcoming RetinUp episode: John and Scott plan to speak with someone from EyePoint Pharmaceuticals to go deeper on the data; additional subgroup analyses will be presented at the Retina Society Annual Meeting, September 23–26, 2026.
Key Takeaways
LUGANO missed its primary endpoint, but EyePoint argues the result was driven by nine atypical patients — not a failure of the drug.
The ad hoc analysis showing non-inferiority is hypothesis-generating, not approval-enabling; LUCIA must be positive for an NDA to proceed.
TKIs work: treatment-free interval data from LUGANO are consistent with SOL-1, reinforcing the class mechanism.
All eyes are on LUCIA in Q4 2026.
Credits
Production & Marketing: Laura Brown | Business Operations: Liz Hogan
🎧 Listen at RetinUp.com | Apple Podcasts | Spotify | YouTube
John and Scott take stock of 2026's biggest retina news — SOL-1 study data assessing Axpaxli (Ocular Therapeutix), FDA approval of Lytenava (Outlook Therapeutics), and the LUGANO study (near) miss for Duravyu (EyePoint Pharmaceuticals) — then look ahead to three imminent late-phase study readouts: Kodiak's DAYBREAK, Merck's BRUNELLO, and Annexon's ARCHER 2. Then Carl J. Danzig, MD, shares what it really costs to leave a practice at mid-career and build something new.
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