Redefining the possible: MCO-010’s 3-year retinal data

Optogenetic gene therapy is emerging as a transformative approach for patients with advanced retinitis pigmentosa (RP) and other inherited retinal degenerations, conditions that have historically offered little more than the promise of managed decline. Nanoscope Therapeutics’ MCO-010, a gene-agnostic intravitreal optogenetic therapy that has been assessed in the phase 2 RESTORE trial (NCT04945772) as well as the follow-up REMAIN study (NCT06162585), has now demonstrated sustained meaningful visual gains through 3 years of follow-up, along with contralateral eye findings that may inform patient selection and the therapy’s long-term clinical role.

In this exclusive Q&A, Modern Retina spoke with Vinit Mahajan, MD, PhD, professor, vitreoretinal surgeon, and scientist in the Department of Ophthalmology and director of the Molecular Surgery and Omics Laboratory at Stanford University, and Sai Chavala, MD, retina specialist, surgeon, and owner of Retina of North Texas and professor at Texas Christian University and the University of Texas Health Science Center. The pair were investigators in the clinical development of the therapy, with Mahajan presenting data recently at the 2026 Association for Research in Vision and Ophthalmology Annual Meeting, held from May 3 to 7, in Denver, Colorado. Together, they discuss what the durability data mean for the field, how MCO-010 fits within a rapidly evolving treatment landscape, and which patients stand to benefit most from this novel restorative approach.

Note: This transcript has been edited for length and clarity.

Modern Retina: What does that gain trajectory from week 52 to week 152 suggest to you about the durability of MCO-010 and/or optogenetic expression in bipolar cells over time?

Vinit Mahajan, MD, PhD: In contrast to the expected 1-line vision loss at 3 years by natural history, the approximate 3-line gain in MCO-010–dosed patients at 3 years and counting speaks to the lasting effect of targeting terminally differentiated bipolar cells. This level of vision gain and durability is a first for patients with advanced retinal degenerations.

MR: Based on the contralateral eye findings, how confident are you about the mechanism of action for this approach, and does that change how you might think about dosing strategy? How meaningful do you feel the safety profile is for retinal specialists following these trials?

Mahajan: Very confident about the mechanism of action. The contralateral findings via neural pathways with MCO-010, and historically with other intraocular gene therapies, are consistent with a retinal transduction approach. With the current data, it doesn’t really change the way I think about dosing. Providers and their patients must discuss which eye to treat first, and then the right timing to treat the second eye as needed.

With no serious adverse events and intraocular inflammation that was easily controllable, safety has been excellent for the MCO-010 program. Considering the very severe vision loss these patients are experiencing and that no other treatments available, the benefit-risk ratio is very much in the patients’ favor.

MR: How do you see MCO-010 fitting into that broader treatment tool kit? Is this a bridge while regenerative therapies mature, a complement to them, or something that stands on its own in the long term?

Sai Chavala, MD: I see MCO-010 as a therapy that can stand on its own in the long term. Its disease- and gene-agnostic mechanism of action allows it to address vision loss in settings where many other approaches may fall short. RP, the lead indication for MCO-010, can be caused by mutations in more than 100 different genes. It is simply not feasible to develop separate gene augmentation therapies for every causative mutation. Luxturna [voretigene neparvovec; Spark Therapeutics], for example, is an important breakthrough, but it addresses only a small subset of inherited retinal degeneration. MCO-010 has the potential to address not only many forms of RP, but other inherited retinal diseases and retinal degenerations as well.

The key point is that MCO-010 is not trying to correct the underlying gene defect. Instead, it targets downstream retinal neurons—specifically bipolar cells—to restore light sensitivity and reinitiate visual signaling after photoreceptors have degenerated. In that sense, it may be relevant across multiple diseases where photoreceptor loss is the final common pathway.

It is also important to recognize that many current or emerging treatments for degenerative retinal disease, including approved therapies such as Syfovre and Izervay, are designed to slow progression rather than restore lost vision. Even if those therapies are successful, patients may still progress to a stage where they need a restorative treatment. That is where an optogenetic approach such as MCO-010 could play a very important role.

MR: Based on what you’ve learned about this treatment to date, where does MCO-010 fit in the emerging RP treatment landscape, and do you see it as complementary to mutation-specific therapies?

Mahajan: Optogenetic therapy could revolutionize treatment of patients with RP who have advanced, severe vision loss who have lost photoreceptors, and especially for those where we don’t know the causative gene, since MCO-010 is gene agnostic. It can complement traditional gene replacement therapy or future neuroprotective modalities that protect against structural retinal damageand slow disease progression. But when the disease is so advanced due to cellular degeneration, optogenetics may be the best option.

MR: The contralateral eye findings somewhat reframe MCO-010 from a unilateral to a potentially bilateral therapy from a single injection. How do you think that changes the patient conversation, and could it shift how you think about which eye to inject first?

Chavala: The contralateral eye findings are very interesting, particularly when considered alongside nonhuman primate ocular gene therapy data from other groups suggesting that intravitreal—but likely not subretinal—gene delivery may reach the fellow eye through the optic nerve and chiasm. This is also consistent with what we know from unilateral intravitreal anti-VEGF therapy, where systemic exposure and, in some cases, biologic effects in the fellow eye have been observed. That said, I do not think these findings materially change the doctor-patient conversation at this point. Similar to anti-VEGF therapy, treatment decisions with MCO-010 should still be made eye by eye, based on factors such as baseline vision, disease severity, ocular comorbidities, and the patient’s functional goals. The possibility of a contralateral effect is scientifically important, but I would not yet use it as the primary basis for deciding which eye to inject first.

What is remarkable is that we are now having this conversation at all. For patients with severe inherited retinal degeneration, who historically have faced a life sentence of progressive vision loss with very limited options, the possibility of discussing meaningful visual improvement, not just halting progression, is extraordinary.

MR: Based on the available data, is there a patient profile where you think the therapy is most likely to deliver meaningful real-world benefit, or perhaps one where you’d currently counsel against it as an option?

Chavala: MCO-010 has been evaluated in patients with severe vision loss, including patients with vision as poor as hand motion or light perception. Despite that advanced disease, patients have experienced meaningful visualgains—on average, approximately the equivalent of 3 lines of vision but some with 6 lines or more.

The real-world functional reports are especially compelling. Patients have described navigating unfamiliar environments with more confidence, seeing loved ones’ faces, and recognizing objects on a table, such as a glass, so they can avoid knocking it over. These may sound like small gains to someone with normal vision, but for patients who have not seen those things in 15 or 20 years, they can be life-changing.

The available data suggest that better baseline vision may be associated with better outcomes, and future studies are expected to evaluate MCO-010 in patients with better starting vision. However, there may be a theoretical ceiling to the level of visual acuity that can be achieved through bipolar cell stimulation. For that reason, at this stage, I would generally think about this therapy for patients with severe functional vision loss or legal blindness, rather than patients who still have relatively preserved central vision.