Streaming Evidence

Real patients, real patterns, real insights. Real-world evidence is here to show how treatments actually play out in the clinic. From massive registries to daily practice patterns, discover how RWE is giving ophthalmologists the insights RCTs can’t.

In a world where Netflix knows your next binge before you do and Spotify can predict your mood with a playlist, it feels a little old-fashioned that medicine still leans so heavily on tightly controlled clinical trials…especially when those studies often leave out the kinds of patients ophthalmologists actually see every day.

Just as streaming platforms reshaped how we consume entertainment by tapping into real-world user data, real-world evidence (RWE) is now set to reshape how we practice ophthalmology. But should it?

Let’s take a closer look at the realm of real-world evidence in eye care, where the rubber of research meets the road of clinical reality.

So, what exactly is real-world evidence?

Before we can decide if real-world evidence deserves a starring role in ophthalmology, it helps to know exactly what we’re talking about. RWE refers to clinical evidence gathered from analyzing real-world data (RWD). In other words, information collected outside the structured environment of randomized controlled trials (RCTs).

“A couple of years ago, we started a real-world registry in Germany,” said Prof. Nicole Eter (Germany) at her EURETINA 2025 lecture.¹ “It’s not only about the retina, it comprises ophthalmology in all the different fields.”

According to Prof. Eter, that registry, named Oregis, now holds data from over two million patients, offering a treasure trove of insight with some jaw-dropping numbers:¹

12.3 million visual acuity assessments
2.6 million procedures
9.5 million prescribed medications
7.2 million diagnoses
13.8 million consultations

This real-world data comes from an array of everyday sources: electronic health records (EHRs), disease registries, insurance claims, patient-reported outcomes, wearable devices, smartphone apps and even social media platforms.¹

The key takeaway? Unlike clinical trials, which operate in controlled conditions, this data reflects what’s actually happening in real clinics, with real patients, in the beautifully messy world of real life.

Why everyone’s talking about real-world evidence

Traditional RCTs may be the gold standard of research, but let’s be honest, they don’t always sparkle in real life. They’re precise, polished and painstakingly controlled…and that control comes at a cost. Enter RWE, stepping into the scene to fill in the gaps that RCTs can’t quite cover.

Here’s why RWE is gaining traction:²

Limited generalizability. RCTs tend to exclude the kinds of patients ophthalmologists actually see in clinic: those with comorbidities, older adults, pregnant women and others who don’t fit the textbook profile.
Cost and time efficiency. Running an RCT can take years (and a small fortune). RWE, on the other hand, can be gathered faster and far more affordably.
Practical clinical insights. Real-world data show treatments hold up when life gets out of hand: when patients skip doses, miss follow-ups or juggle multiple conditions.
Long-term outcomes. RWE can follow patients over extended periods, painting a more complete picture of how treatments perform over time.
Rare conditions. For uncommon ophthalmic diseases, where it’s nearly impossible to recruit enough participants for a traditional trial, RWE can be the key to unlocking new understanding.

“We are just in the beginning of analyzing our data, and this data grows every day as we have more centers to contribute,” Prof. Eter pointed out. “Comparing your own data to the rest of the registry data may enable you to preserve or change your treatment regimen and then, of course, get better.”

In short, RWE isn’t here to replace traditional trials. It’s here to make them smarter, faster and a whole lot more reflective of the real world.

Real-world evidence in action

So, what happens when all this data actually hits the clinic? According to Prof. Eter, Oregis offers a glimpse into how RWE is changing the ophthalmic game, starting with neovascular age-related macular degeneration (nAMD).

In its first year of tracking treatment patterns, the registry found that patients attended an average of 9.4 appointments, effectively addressing long-standing concerns about undertreatment back in the early days of intravitreal injections.¹

The data also shed light on real-world treatment intervals. “The interval between the intravitreal injections [is] basically 28 days. So this load up of monthly injections appears to be really efficient in the real world,” Prof. Eter noted. “And then there is an average of 42 days for the next three injections.”

And Germany isn’t the only country getting in on the RWE action. Around the world, ophthalmology registries are showing just how powerful real-world data can be:

The IRIS Registry. The American Academy of Ophthalmology’s IRIS (Intelligent Research in Sight) Registry has mined RWE to explore everything from cataract surgery outcomes to rare diseases, like identifying 27,339 eyes with giant cell arteritis to determine whether the condition’s incidence varied by season (spoiler: it didn’t).³
IIH Registries. For idiopathic intracranial hypertension, multiple registries have helped reveal prognostic factors, track disease behavior across patient subgroups and assess the safety of medications during pregnancy.⁴
MSBase Registry. This international database provided valuable real-world insights, showing that acute treatment improved visual outcomes and reduced the risk of progression to MS in patients with acute optic neuritis.⁵

The streaming service approach

If Netflix has taught us anything, it’s that one size definitely doesn’t fit all. Just as the platform tailors recommendations to your viewing habits (true crime binge, anyone?), RWE reminds us that not every patient with the same diagnosis should receive the exact same treatment.

The German registry data on AMD treatment switching drives that point home. “Here you can see the total number of patients who underwent a switch of intravitreal agents,” Prof. Eter noted. “So that was over 6,000, and more than 1,000 patients switched two times.”

That’s not just an interesting statistic. It’s a window into how real-world practice actually unfolds. In the regimented world of traditional clinical trials, switching therapies midstream is often a no-go. But in real life? It happens all the time. And RWE captures those nuances beautifully, showing clinicians what truly works for individual patients, not just the average one.

When the algorithm glitches

Before we toss our beloved RCTs out the window and declare RWE the new ruler of research, let’s remember: even Netflix occasionally suggests a show we’d never watch. RWE, for all its promise, comes with its own set of quirks and complications.

Here are some of the main challenges that can throw off the algorithm:²

Data quality and standardization. RWD isn’t collected under the same tightly controlled conditions as RCTs. That means inconsistent entries and messy datasets can sometimes muddy the picture.
Selection bias and confounding factors. Without randomization, results can easily be skewed by who gets included and who doesn’t.
Missing data. Incomplete records are the bane of RWE. Some variables just aren’t consistently tracked across every patient.
Privacy concerns. Patient data is powerful, but protecting it requires airtight security and ethical oversight.
Interoperability issues. Integrating data from different systems and formats can feel a bit like trying to get Spotify and Apple Music to share playlists.

As Kodra et al.⁶ puts it, “The quality of data in rare disease registries may be compromised by several factors, including the low prevalence of disease which can limit statistical power and reliability of the data, and variability in data collection influencing the accuracy of the information gathered.”

So, while RWE gives us a bigger, more dynamic picture of clinical life, it’s not without its fuzzy pixels.

Finding the right balance

It doesn’t have to be a cage match between RWE and RCTs. In fact, most experts agree the smartest approach is to use both…kind of like checking both Netflix’s “Top Picks for You” and the critics’ reviews before committing to a two-hour movie.

“We should use all the tools in our tool chest and use knowledge from all sources in an iterative and synergetic fashion,” Johnson & Johnson Chief Medical Officer Joanne Waldstreicher said in Examining the Impact of Real-World Evidence on Medical Product Development.⁷

So what does this partnership actually look like in practice? Think of it as research teamwork:⁸

RWE to inspire, RCTs to confirm. Use RWD to generate hypotheses that can later be tested in controlled trials.
RCTs for proof, RWE for perspective. Let RCTs establish efficacy, turn to RWE to see how those results hold up in broader, messier real-life populations.
Long-term safety checks. After a treatment wins approval through RCTs, RWE can keep tabs on how it performs over time.
When RCTs can’t cut it. For rare conditions or emergency settings where traditional trials aren’t feasible, RWE can fill critical knowledge gaps.

In the end, it’s not about choosing sides, it’s about blending the precision of RCTs with the practicality of RWE to create a clearer, more complete picture of patient care.

Regulatory perspectives

Regulatory bodies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are starting to give RWE a serious seat at the table. While RCTs remain the gold standard for proving efficacy, regulators increasingly recognize that RWE offers invaluable complementary insights, especially when it comes to safety monitoring and understanding how treatments perform outside the tidy world of clinical trials.⁹

Regulatory acceptance of RWE is steadily evolving, with some agencies now leveraging it to:⁹

Accelerate approval for certain treatments
Extend approved indications to broader patient populations
Add safety information to drug labels
Monitor post-marketing safety and outcomes

Implementing RWE in your practice

For eye care professionals interested in incorporating RWE into their practice, here are some practical steps:⁸

Participate in registries. Contributing to initiatives like IRIS doesn’t just help researchers. It helps build the evidence base that will guide future practice.
Compare your outcomes. As Prof. Eter noted, looking at your own data alongside registry results can highlight patterns in your treatment approach and reveal opportunities for improvement.
Stay informed. Keep up with publications and studies that use RWE in your specialty area. Knowledge is power, after all.
Combine evidence sources. Don’t ditch RCTs. They provide essential efficacy data. Instead, let RWE complement RCT findings for a fuller picture of patient care.
Discuss with patients. Sharing relevant RWE with patients can make your consultations more personalized, especially when RWD better reflects their individual circumstances than traditional trials.

Just as streaming services haven’t completely replaced traditional television—but have definitely changed how we consume content—real-world evidence won’t replace RCTs, but it will transform how we generate and apply evidence in ophthalmology.

The real question isn’t whether RWE should influence our practice, but rather how to blend it with other forms of evidence to deliver the best patient care. As registries like Oregis show, RWE offers insights that complement and extend what RCTs teach us.

The goal isn’t to pick sides between trial types. Instead, it’s about using all available data, from tightly controlled studies to messy, real-world practice, to make smarter, patient-centered decisions. Just like consulting both critics’ reviews and viewer ratings before choosing your next binge-worthy show, combining RCTs and RWE gives clinicians the clearest picture for clinical decision-making.

The data is out there – it’s up to us to stream it wisely.

Editor’s Note: Prof. Nicole Eter’s insights in this article are based on her Day 3 presentation at EURETINA 2025 Paris, titled “Recent Advances in the Management of AMD That Are Changing Our Clinical Practice.” This content is intended exclusively for healthcare professionals. It is not intended for the general public. Products or therapies discussed may not be registered or approved in all jurisdictions, including Singapore. A version of this article was first published in PIE Issue 37.

References

Eter N. Should Real-World Evidence Change Our Practice? Lecture at EURETINA 2025. Paris, France. September 6, 2025.
Costa V, Custodio MG, Gefen E, Fregni F. The relevance of the real-world evidence in research, clinical and regulatory decision making. Front Public Health. 2025;13:1512429.
Wladis EJ, Ata A, Li C, et al. The impact of month and season on the incidence of giant cell arteritis: an Intelligent Research in Sight (IRIS) Registry analysis. Graefes Arch Clin Exp Ophthalmol. 2024;262(2):609-614.
Thaller M, Homer V, Mollan SP, Sinclair AJ. Disease course and long-term outcomes in pregnant women with idiopathic intracranial hypertension: The IHH Prospective Maternal Health Study. Neurology. 2023;100(15):e1598-e1610.
Kenney R, Liu M, Patil S, et al; MSBase Study Group. Long-term outcomes in patients presenting with optic neuritis: Analyses of the MSBase registry. J Neurol Sci. 2021;430:118067.
Kodra Y, de la Paz MP, Coi A, et al. Data quality in rare disease registries. Adv Exp Med Biol. 2017;1031:149-164.
National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press.
Blonde L, Khunti K, Harris SB, Meizinger C, Skolnik NS. Interpretation and impact of real-world clinical data for the practicing clinician. Adv Ther. 2018;35(11):1763-1774.
Alipour-Haris G, Liu X, Acha V, Winterstein AG, Burcu M. Real-world evidence to support regulatory submissions: A landscape review and assessment of use cases. Clin Transl Sci. 2024;17(8):e13903.