This Week in Ophthalmology — May 28, 2026

Welcome to This Week in Ophthalmology. This week we're covering nine notable papers spanning the management of chronic retinal disease, new insights in cataract and cornea, and innovative approaches to diagnostics and future therapies. Let's dive in.

Medical Retina

We begin in medical retina, where the management of chronic, exudative diseases continues to evolve. A major focus remains on reducing treatment burden for patients with neovascular age-related macular degeneration, or nAMD. A new study in Retina provides real-world data on switching previously treated patients to high-dose aflibercept 8 milligrams [1]. This retrospective study looked at 654 eyes that were in a plateau phase, having already received an average of 35 prior anti-VEGF injections. The switch appeared to improve anatomical outcomes. At the time of the switch, 55% of maculae were dry. This figure jumped to 76% at 3 months and remained significantly improved at 69% by the 12-month mark. The switch also allowed for significant treatment interval extension. The proportion of eyes needing injections every 3 to 5 weeks dropped from 46% to just 18%, while the proportion on 9 to 12-week intervals tripled from 11% to 34%. The mean treatment interval increased by nearly two weeks. However, there's a crucial note of caution: best-corrected visual acuity showed a small but statistically significant decline of about one letter over the year. Even in eyes that were dry at the time of the switch, vision decreased by an average of nearly two letters. The authors conclude that while high-dose aflibercept improves anatomy and reduces treatment frequency, the slight decline in vision warrants careful long-term follow-up.

While we seek to optimize treatment schedules, predicting which patients will respond well in the first place remains a key challenge, particularly in diabetic macular edema, or DME. A scoping review in the Survey of Ophthalmology systematically examined OCT biomarkers for predicting anti-VEGF treatment outcomes [2]. The review, which included 13 studies and over 1,100 eyes, found two predictors to be consistently associated with poorer visual outcomes: disorganization of the retinal inner layers, known as DRIL, and disruption of the retinal outer layers, or DROL, which includes the ellipsoid zone and external limiting membrane. The presence of these biomarkers at baseline was a strong negative prognostic indicator, with reported odds ratios for poor outcomes ranging from nearly three to almost nine. Conversely, the resolution of DRIL and DROL during treatment correlated with visual recovery. This review reinforces the clinical utility of carefully evaluating these OCT features to help set realistic expectations for patients with DME starting anti-VEGF therapy.

Moving from treatment response to long-term prognosis, a study in JAMA Ophthalmology explores how the physical shape of the eye influences outcomes in high myopia [3]. This was a 15-year prospective cohort study from China that used high-resolution MRI to classify highly myopic eyes into six 3D shapes. They found that globe morphology was a powerful predictor of progression. Eyes with spheroidal shapes had the slowest rate of axial elongation, while eyes classified as 'nasally distorted' had the fastest. After adjusting for other factors, nasally distorted eyes elongated significantly faster and had a nearly six-fold higher odds of rapid elongation. Furthermore, eyes with any type of 'deformed' shape—including conical, nasally distorted, temporally distorted, or barrel-shaped—had a seven-fold higher risk of developing macular choroidal thinning. The nasally distorted and conical shapes carried the greatest risks for both choroidal thinning and progression of myopic macular degeneration. These findings suggest that baseline 3D eye shape could be a valuable tool for risk stratification and personalized management in patients with high myopia.

Rounding out our retina section, the Multimodal Imaging in Uveitis, or MUV, Taskforce has published new evidence- and consensus-based guidelines on imaging in Vogt-Koyanagi-Harada disease, or VKH [4]. Published in Ophthalmology Retina, the report emphasizes the critical role of multimodal imaging beyond just clinical examination. The experts reached consensus that for diagnosis of active, early-stage VKH, key findings include bilateral serous retinal detachments on OCT and characteristic round-to-oval hypofluorescent dots on indocyanine green angiography, or ICGA. For monitoring disease, both OCT and ICGA were deemed highly sensitive for detecting disease activity, including subclinical reactivation that might be missed on exam alone. Fluorescein angiography remains useful for identifying pinpoint leakage and optic nerve staining. Interestingly, the taskforce considered fundus autofluorescence to be of limited utility for diagnosis. The guidelines provide a structured framework for using these tools to improve diagnostic accuracy and detect vision-threatening complications like choroidal neovascularization earlier.

Cataract and Cornea

Now, we turn to the anterior segment, starting with a common challenge in cataract surgery: IOL power calculation in extremely long eyes. A study in the American Journal of Ophthalmology evaluated the accuracy of eight modern formulas in 330 Asian eyes with an axial length of 32 millimeters or greater [5].

The Study Investigators retrospectively analyzed outcomes, splitting the cohort into a 'Main Group' with axial lengths between 32 and 35 millimeters, and a small 'Ultra-Long Group' with axial lengths over 35 millimeters. The formulas assessed were the Barrett Universal II, Cooke K6, EVO 2.0, Hill-RBF 3.0, Kane, Pearl-DGS, Hoffer QST, and Zhu-Lu.

Results In the main group, no single formula was superior on all metrics. The Zhu-Lu formula had the lowest root mean square absolute error, while the Cooke K6 had the lowest median absolute error. The Pearl-DGS formula had the highest percentage of eyes within a half diopter of target. In contrast, the Hoffer QST formula performed the worst across the board, showing the largest errors and a significant hyperopic drift with increasing axial length. In the small ultra-long group, Zhu-Lu and Cooke K6 also performed very well. The authors conclude that for these exceptionally long eyes, clinicians should favor formulas like the Cooke K6, EVO, Pearl-DGS, and Zhu-Lu, while the Hoffer QST should likely be avoided.

Staying in the anterior segment, a paper in Ophthalmology addresses the difficult task of predicting disease progression in Fuchs Endothelial Corneal Dystrophy, or FECD [6]. Currently, it's hard to know which patients will eventually require keratoplasty. This study demonstrates that a genomic risk profile, which combines the patient's CTG18.1 expansion status with a disease-specific polygenic risk score, can effectively predict the risk of needing surgery. The findings were validated across independent patient cohorts, suggesting that this type of genetic profiling could soon play a role in counseling patients and planning for potential future intervention.

Diagnostics, Systems, and Future Therapies

Our final section looks at innovations in diagnostics, healthcare delivery, and therapeutics. First, a paper from the American Journal of Ophthalmology tackles a common logistical problem in neuro-ophthalmology: how to get urgent neuroimaging for patients with optic disc edema without sending everyone to the emergency department [7]. The investigators at the Wilmer Eye Institute analyzed their dedicated outpatient STAT neuroimaging pathway and compared its cost and efficiency to the traditional ED-based route. Using a detailed time-driven activity-based costing method, they found the outpatient STAT pathway was significantly better on both fronts. The median cost per patient was 20% lower—$285 versus $355—driven by savings in personnel and facility costs. Even more striking was the time savings: the median visit duration was 70% shorter in the outpatient pathway, taking just under 2 hours compared to nearly 6.5 hours in the ED. This study provides a strong economic and efficiency argument for establishing similar outpatient pathways to reduce healthcare costs and alleviate the burden on busy emergency departments.

Broadening our view of patient assessment, another paper in JAMA Ophthalmology seeks to establish a clinically relevant threshold for impaired contrast sensitivity in older adults [8]. While we routinely measure visual acuity, contrast sensitivity is a critical, often-overlooked aspect of functional vision. Using data from the National Health and Aging Trends Study, a large, nationally representative cohort of United States Medicare beneficiaries, researchers linked binocular contrast sensitivity to self-reported visual disability, such as difficulty recognizing faces or reading a newspaper. They found that each 0.1-unit decrease in log contrast sensitivity was associated with a 12% higher odds of developing visual disability within one year. Using ROC curve analysis, they identified an optimal threshold of 1.60 logCS. This value best discriminated between those with and without functional visual problems, though with moderate sensitivity and specificity. This functionally anchored cutoff provides clinicians with a benchmark for interpreting contrast sensitivity measures and identifying patients who may be struggling with daily visual tasks despite having good acuity.

Finally, we look to the future of treatment with a paper in Science Translational Medicine on controllable gene editing [9]. A major safety concern with CRISPR-Cas systems is the risk of off-target edits. This research introduces a new system called PRINCE, which makes both the nuclease and the guide RNA inducible by small-molecule drugs. In essence, it creates an 'on-switch' for gene editing, allowing for precise temporal control. The team developed a compact version called 'Little Prince' that can be delivered in a single adeno-associated virus vector. In a humanized mouse model of neovascular AMD, administration of the drug inducer activated the system, leading to a significant reduction in lesion size and leakage. Importantly, this controlled system showed a marked reduction in off-target activity compared to constitutive, or 'always-on', editors. This work represents a significant step towards safer in vivo therapeutic gene editing for ocular diseases like nAMD.

Editor's Pick

If you only have time for one paper this week, make it the real-world study on switching to aflibercept 8 milligrams in Retina [1]. This paper provides immediate, practical insights for any clinician managing nAMD, balancing the anatomical benefits and extended intervals of the new formulation against a cautionary signal of a slight decline in visual acuity at one year.

Clinical Bottom Line

Here are the key takeaways from this week in Ophthalmology.

First: When switching nAMD patients to high-dose aflibercept, you can expect drier maculas and longer treatment intervals, but be sure to monitor vision closely, as a small decline was observed in this real-world cohort at 12 months [1].

Second: In patients with diabetic macular edema, the presence of DRIL or DROL on a baseline OCT is a strong predictor of poorer visual outcomes with anti-VEGF therapy and can help in counseling patients [2].

Third: For cataract surgery in eyes with an axial length over 32 millimeters, modern IOL formulas like Cooke K6, EVO, Pearl-DGS, and Zhu-Lu are preferable, while the Hoffer QST formula should be avoided due to significant hyperopic errors [5].

Fourth: For medically stable patients with optic disc edema, an outpatient STAT MRI pathway is a significantly faster and more cost-effective alternative to an emergency department visit for neuroimaging [7].

And finally: In older adults, a contrast sensitivity value below 1.60 logCS may represent a functional threshold for visual disability, providing a useful benchmark for clinical assessment [8].

That's your roundup for This Week in Ophthalmology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.