EURETINA 2026: Uveitis or retinitis pigmentosa? Ester Carreño, MD, PhD, on mimics

Distinguishing retinitis pigmentosa (RP) from inflammatory disease can be difficult when an inherited retinal dystrophy presents with features that suggest uveitis or when an inflammatory process leaves behind an RP-like phenotype. Ester Carreño, MD, PhD, a consultant ophthalmologist specialising in uveitis at University Hospital La Paz in Madrid, Spain, explored this overlap on 2 October at EURETINA 2026 in Vienna, Austria. Her presentation, "Is it really retinitis pigmentosa?" was part of the symposium, "Survival guide for the retina specialist: when retinal diseases pretend to be something else,” Carreño, who leads clinical research for the hospital's uveitis and ocular inflammation programme, first encountered this diagnostic challenge during her medical retina and uveitis fellowship at Moorfields Eye Hospital in London, where patients with nearly identical presentations could receive different diagnoses depending on whether they attended the genetics or uveitis clinic.

In conjunction with her presentation, Carreño answered questions from Ophthalmology Times Europe about the overlap between inherited and inflammatory retinal disease. In the following Q&A, Carreño discusses why this differential belongs in a survival guide for retina specialists, the clinical and imaging features that separate inflammation from inherited retinal dystrophy, what drives the misdiagnosis of inherited disease as uveitis and its consequences for patients, the treatable or clinically important mimics to rule out before diagnosing RP and how expanding gene-based therapies have raised the stakes for genetic confirmation.

This Q&A has been lightly edited for length and clarity.

Ophthalmology Times Europe (OTE): What prompted the focus on the overlap between uveitis and retinitis pigmentosa for this session, and why does this differential deserve a place in a survival guide for retina specialists?

Ester Carreño, MD, PhD: I guess the first time I really encountered the difficulty of this differential diagnosis was during my fellowship at Moorfields Eye Hospital. I was surprised to see what seemed to be exactly the same patient suddenly being diagnosed with unilateral retinitis pigmentosa (RP) if we were in the genetics clinic, or with acute zonal occult outer retinopathy (AZOOR) if we were in the uveitis clinic.

I think we still don’t have all the answers. The unilateral RP-like phenotype remains a matter of debate: can a genetic disease really manifest in only one eye, or are we sometimes dealing with an inflammatory condition that is mimicking an inherited retinal dystrophy? On the other hand, we know that asymmetric or unilateral presentations can occur in some genetic diseases, such as Best disease.

That uncertainty is precisely why I think this differential deserves a place in a survival guide for retina specialists. These patients can move between the uveitis and inherited retinal disease clinics, and reaching the right diagnosis can be challenging but can be crucial for both management and prognosis.

Furthermore, in many patients with RP, we see some degree of inflammation, which we usually assume is secondary to the underlying retinal degeneration. However, in cases with late-onset disease and non-informative genetic testing, there is always the question of whether we are dealing with a purely genetic disease or whether there is an immune-mediated ocular disease contributing to the picture.

This is particularly important because the diagnostic distinction has direct implications for treatment. If there is an inflammatory component that we can identify and treat, we may have a therapeutic opportunity that we would otherwise miss.

And this also raises another question: why should a genetic disease necessarily be progressive, with an initially normal-looking ellipsoid zone gradually disappearing over time? Could the immune system actually be playing a role in this progression? I think these are questions that we still need to answer.

OTE: Across the cases selected for the presentation, what clinical, imaging, or history features ultimately separated an inflammatory process from an inherited retinal dystrophy? What red flags should prompt a retina specialist to question an existing diagnosis of retinitis pigmentosa or uveitis?

Carreño: In my opinion, one of the main clues is symmetry. Bilateral and highly symmetric disease should make us think about an inherited retinal disorder. Wide-field fundus autofluorescence is particularly useful for assessing symmetry, and it can give us a lot of information about the underlying diagnosis.

There are also a couple of conditions where the overlap between inherited retinal disease and inflammation is particularly relevant. One is CRB1-associated retinal dystrophy. In these patients, we commonly see a very disorganized retina, with increased retinal thickness (in contrast to the thinning that we see in most forms of RP) as well as macular oedema. The clues are the early onset, the non-inflammatory appearance of the macular oedema (for example the absence of subfoveal subretinal fluid) and the increased thickness and disorganization of the retinal layers even in areas without macular oedema.

Another important example is birdshot chorioretinitis. In late-stage disease, there can be significant loss of the ellipsoid zone, which can mimic an RP phenotype. In addition to HLA-A29 positivity, indocyanine green angiography can be particularly helpful, because it reveals the characteristic choroidal involvement, with multiple round or oval hypofluorescent lesions.

So, in ambiguous cases, I think we should always step back and look at the overall phenotype rather than relying on a single finding.

OTE: In cases where an inherited retinal dystrophy is initially managed as uveitis, what tends to drive that misdiagnosis, and what are the consequences for the patient?

Carreño: I think the main thing that drives this misdiagnosis is the presence of macular oedema. It can easily be interpreted as an inflammatory manifestation. This is particularly relevant in conditions such as CRB1-associated retinal dystrophy, where macular oedema can be quite prominent. In these patients, the oedema may lead us to start corticosteroids or other immunosuppressive treatments, even though the underlying disease is genetic. One of the clues that should make us question the diagnosis is an unexpected or inconsistent response to treatment. In many of these cases, the patient shows little or no response, which should prompt us to go back and reassess the phenotype and the diagnosis.

The consequences can be significant. The patient may be exposed to unnecessary immunosuppressive treatment without addressing the underlying disease. More importantly, the correct diagnosis may be delayed, including genetic confirmation and genetic counselling. And this is becoming increasingly relevant as access to clinical trials and potentially gene-specific therapies depends on having an accurate diagnosis.

OTE: Which treatable or clinically important conditions are most important to rule out before a diagnosis of retinitis pigmentosa is made, and how should the workup be approached when the presentation is ambiguous?

Carreño: I guess the real challenge is autoimmune retinopathy (AIR), and particularly cancer-associated retinopathy (CAR).

In AIR, it is true that many treatments have limited success in preventing the progressive loss of retinal function. But in CAR, there is an additional and very important issue: we need to look for an underlying malignancy. Identifying a previously unknown cancer can be crucial for the patient, and in some cases the ocular presentation may actually be the first sign of the disease.

Another major challenge is how we assess treatment response. It is very difficult to evaluate the effect of a treatment in a disease where we do not fully understand the natural history, in particular, whether the disease is actually progressing and, if so, how quickly. Without knowing the expected rate of progression, it becomes very difficult to determine whether a treatment is truly modifying the course of the disease or whether we are simply observing its natural variability.

So, in ambiguous cases, I think the workup needs to be comprehensive and multidisciplinary, and we need to be particularly careful not to label a patient as having RP before excluding potentially treatable or clinically important mimics.

OTE: With gene-based therapies and clinical trials expanding for inherited retinal diseases, how has the importance of an accurate diagnosis and genetic confirmation changed?

Carreño: Genetic confirmation is essential when we are considering a treatment that targets a specific mutation. In those cases, we need to know exactly which genetic defect is responsible for the disease in order to determine whether the patient is eligible for a particular therapy or clinical trial.

But genetic confirmation is also becoming increasingly relevant for mutation-agnostic treatments. Even when the treatment does not target a specific mutation, confirming the underlying genetic diagnosis is important because these therapies can be associated with a significant inflammatory response, and this may potentially be more problematic in patients with an underlying inflammatory or immune-mediated component.

So, I think that, with the expansion of gene-based therapies and clinical trials, we have moved from asking simply, “Does this patient look like RP?” to asking, “What exactly is the disease, what is causing it, and can we confirm it genetically?” An accurate diagnosis is becoming increasingly important not only for prognosis, but also for treatment selection, clinical trial eligibility, and patient counselling.