Research papers

The research behind the news.

Papers we often share with patients in clinic, each with a short summary in plain language. Click a title to read the full paper.

Genes and what to expect.

A genotype-phenotype correlation matrix for ABCA4 disease based on long-term prognostic outcomes

Lee W, Zernant J, Su PY, Nagasaki T, Tsang SH, Allikmets R. JCI Insight, 2022.

We often print this in clinic
Keyword: Winston

In plain language: Stargardt disease and other ABCA4 diseases can be very mild or very severe, depending partly on which two ABCA4 gene changes a person has. The team studied 112 people aged 50 or older, so they could see how each person's disease looked after many years. They sorted people into four groups, from milder disease limited to the center of the retina to severe disease across the whole retina, and linked common gene changes to each group. Some changes, such as G1961E and a group of 'mild' changes, usually lead to milder disease no matter what the other change is.
What it means for patients: If you know your two ABCA4 changes, this study can help your doctor estimate how your disease may progress over the long term. It gives likelihoods, not certainties: people with the same changes can still differ. Bring your genetic test report and ask your doctor what your changes suggest.

DOI: 10.1172/jci.insight.156154

Gene therapy.

Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR

Cehajic-Kapetanovic J, Xue K, Martinez-Fernandez de la Camara C, et al. Nature Medicine, 2020.

We often print this in clinic
Keyword: MacLaren

In plain language: The first study in people of a gene therapy for X-linked RP caused by changes in the RPGR gene. Eighteen men had surgery to place a healthy copy of RPGR under the retina. The treatment was generally safe at lower doses, and some people's side vision improved over 6 months.
What it means for patients: It showed that gene therapy for RPGR is possible. Later, larger studies of this treatment did not meet their main goal, and other RPGR gene therapies are still being tested. Ask your doctor about current RPGR studies.

DOI: 10.1038/s41591-020-0763-1

New CRISPR tools to correct pathogenic mutations in Usher syndrome

Major L, McClements ME, MacLaren RE. International Journal of Molecular Sciences (review), 2022.

We often print this in clinic

In plain language: A review from the University of Oxford. The USH2A gene, the most common cause of Usher syndrome type 2, is about three times too big to fit in the virus (AAV) used for most eye gene therapies, so a healthy copy cannot simply be added. The authors explain how newer, smaller CRISPR gene-editing tools, such as base editors and prime editors, could fix the specific spelling mistake in a person's own USH2A gene instead.
What it means for patients: This explains why USH2A gene therapy is harder than for genes like RPE65, and what researchers are working on. When the review was written, these editing tools were still being developed in the lab. A different approach, an RNA therapy for changes in exon 13 of USH2A (ultevursen), is being tested in people; see our trials page.

DOI: 10.3390/ijms231911669

Treatments for any gene.

CRISPR editing of anti-anemia drug target rescues independent preclinical models of retinitis pigmentosa

Nolan ND, Cui X, Robbings BM, et al., Hurley JB, Tsang SH. Cell Reports Medicine, 2024.

We often print this in clinic
Keyword: Nolan

In plain language: Rods use energy in an unusual way. In mice with two different kinds of RP, turning off an enzyme called PHD shifted how rods use energy and helped the retina survive longer. Medicines that block PHD are already approved for anemia, and gene editing worked even better than the medicines.
What it means for patients: This is lab research in mice. It points to a way to treat RP regardless of the gene, but it has not been tested in people. Please do not take anemia medicines for your eyes; they can have serious side effects.

DOI: 10.1016/j.xcrm.2024.101459

Cell and stem cell therapy.

Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies

Schwartz SD, Regillo CD, Lam BL, et al., Del Priore LV. Lancet, 2015.

We often print this in clinic
Keyword: Astellas

In plain language: Eighteen people, nine with Stargardt disease and nine with dry age-related macular degeneration, had support cells (RPE) grown from embryonic stem cells placed under the retina. They were followed for about two years. The cells caused no tumors and no rejection, and most problems came from the surgery and the immune-suppressing medicines. Some treated eyes read more letters on the eye chart, and the untreated eyes did not show the same change.
What it means for patients: It was the first good evidence that cells made from stem cells can be placed in the eye safely over the medium to long term. It was a small safety study and was not designed to prove that vision improves. This program is now run by Astellas, which is testing a newer cell product (ASP2020) for Stargardt-type macular dystrophies.

DOI: 10.1016/S0140-6736(14)61376-3

Transplantation of human embryonic stem cell-derived retinal pigment epithelial cells in macular degeneration

Mehat MS, Sundaram V, Ripamonti C, et al. Ophthalmology, 2018.

Keyword: Astellas

In plain language: The UK arm of the same stem cell program. Twelve people with advanced Stargardt disease received up to 200,000 stem cell-derived RPE cells under the retina. Dark patches that may be the new cells appeared in every person and lasted. Detailed tests of the treated area showed no benefit to vision at 12 months, and in one person at the highest dose the treated area became thinner and less sensitive.
What it means for patients: It shows why careful testing of the treated spot matters, not just the eye chart. The cells were safe overall, but they did not help vision in advanced disease. The authors advise caution about treating earlier stages until more is known.

DOI: 10.1016/j.ophtha.2018.04.037

Retinal pigment epithelium and microglia transplantation in age-related macular degeneration

Surawatsatien N, Solanky RM, van de Werken RP, Kong M, Diaconita V, Tsang SH. American Journal of Ophthalmology, 2026.

We often print this in clinic
Keyword: Max Kong

In plain language: A review from our group of how stem cells might rebuild the back of the eye in advanced macular degeneration. It compares ways of making and placing support cells (RPE), from single-cell injections to thin cell patches, and the risks of each. It also covers transplanting microglia, the retina's immune cells, and gene editing the cells so the body does not reject them or so they lose a genetic risk factor.
What it means for patients: This summarizes research that is still mostly in the lab or in early safety studies. It focuses on age-related macular degeneration, but the same cell approaches are being tested for inherited conditions such as Stargardt disease. No stem cell treatment for the retina is approved yet; be cautious of clinics that sell unproven stem cell injections.

DOI: 10.1016/j.ajo.2026.07.036

Everyday health.

Aerobic exercise protects retinal function and structure from light-induced retinal degeneration

Lawson EC, Han MK, Sellers JT, Chrenek MA, Hanif A, Gogniat MA, Boatright JH, Pardue MT. Journal of Neuroscience, 2014.

We often print this in clinic
Keyword: exercise

In plain language: Mice that ran on a treadmill for an hour a day, 5 days a week, kept about twice as many light-sensing cells and twice as much retinal function after a damaging dose of bright light as mice that did not exercise. Exercise raised the level of BDNF, a natural protein that helps nerve cells survive; blocking BDNF removed the benefit. Later studies from the same group and others saw similar protection in mice with inherited retinal degeneration.
What it means for patients: This is mouse research, and exercise has not yet been tested as a treatment for inherited retinal disease in people. Regular exercise is good for your overall health, so it is a reasonable habit if your doctor agrees. Choose activities that are safe for your vision, such as walking with a partner, a stationary bike or swimming.

DOI: 10.1523/JNEUROSCI.2062-13.2014

A single study rarely settles a question. Many of these papers describe early or animal research. Please talk with your retina specialist before making any decision about treatment.