Audio link: 

https://open.spotify.com/episode/6SRO6nppcTdCE3FvzpT2Z7?si=2C2cwAleTDuc9DCR1sCGgw 

In this week’s issue

• Ocular point-of-care ultrasound performed by emergency department physicians does not significantly reduce the number of ophthalmology consults for eye-related chief complaints.
• Routine glaucoma follow-up appointments may be delayed up to 60 days among patients with mild, stable disease. Those with moderate or severe disease may have greater odds of progression. 
• Both the SII and INFLA-scores for systemic inflammation demonstrated significant, dose-dependent relationships with increased incidence of cataract formation, POAG, AMD, and DR, and were associated with retinal thinning on OCT.
• Intravitreal injections of KIO-301, a photoswitch molecule designed to make surviving retinal ganglion cells responsive to light in retinitis pigmentosa, demonstrate a favorable safety profile and early signs of functional vision improvement regardless of underlying gene mutation in the ABACUS-1 trial. 

Ophthalmology

Does ocular POCUS in the ED decrease ophthalmology consults?

Emergency department ocular ultrasound may not be worth the trouble. At institutions across the country, emergency department physicians have been encouraged to perform ocular point-of-care ultrasound (POCUS) for patients presenting with undifferentiated ocular injuries prior to placing an ophthalmology consult. The idea behind these efforts is that POCUS may reduce the number of ophthalmology consults placed while still providing high-quality care for patients. New evidence from a group of Vanderbilt researchers, however, suggests this is unlikely. In this retrospective, cross-sectional study, researchers analyzed records from 282 patients presenting to the ED between 2021 and 2024. All patients had an eye-related chief complaint, and all received both ocular POCUS in the ED and an ED or outpatient ophthalmology consultation. This study found that 91.5% of patients who received ED POCUS were referred to ophthalmology, including 82.6% with unremarkable POCUS results. There was only moderate agreement between the diagnosis made by POCUS and that made by consulting ophthalmologists. Point-of-care ultrasound had high sensitivity (sn) for detecting vitreoretinal pathology, such as retinal detachments (sn = 93.8%) and vitreous hemorrhages (sn = 73.0%). Several vision-threatening conditions were not diagnosed by POCUS. These data suggest that ED ocular POCUS does not significantly reduce ophthalmology consults and does not achieve satisfactory diagnostic accuracy in the majority of cases.

JAMA Ophthalmology 

Comparing the diagnostic accuracy of retinal birefringence and traditional autorefractor devices

Tried, tested, and true. The detection of preventable vision loss in children has traditionally used autorefractors to identify amblyopia risk factors; however, prior studies have shown variable sensitivity and specificity, leading to over-referral of patients. Retinal birefringence scanning devices, including the Blinq vision scanner, were developed to directly detect amblyopia by identifying differences in binocular foveation. The authors conducted a prospective, masked diagnostic accuracy study at a single institution comparing the retinal birefringence scanner with a traditional autorefraction photoscreening device in pediatric patients. Of 195 enrolled participants, 139 completed screening with both devices. The traditional autorefraction device demonstrated significantly higher sensitivity than the retinal birefringence scanner for detecting amblyopia (90% vs 62%) and visually significant refractive error (95% vs 54%), with no significant difference identified for strabismus detection. Specificity was comparable between devices. Furthermore, the area under the receiver operating characteristic curve was greater for the autorefraction device across all vision disorders, particularly amblyopia. These findings demonstrate that traditional autorefraction devices offer greater sensitivity and comparable specificity to retinal birefringence scanners, suggesting their reliability for pediatric vision screening.

American Journal of Ophthalmology 

Could some glaucoma patients safely go longer between visits?

Keeping a close eye on glaucoma is important, but maybe not for every patient. Glaucoma management relies on close monitoring, with frequent follow-up visits to detect progression early. Concerns about delayed detection of progression have led many clinicians to schedule frequent examinations for nearly all glaucoma patients, potentially increasing the burden on both patients and ophthalmology clinics. This retrospective study investigated whether delayed follow-up appointments are associated with disease progression in patients with open-angle glaucoma or glaucoma suspects. Researchers analyzed 1121 eyes (600 patients) who underwent at least 5 Humphrey Visual Field tests between 2014 and 2023 at a tertiary academic center. The mean recommended follow-up interval was approximately 166.8 days, and 53.4% of the visits occurred after the provider-recommended timeframe. Delayed follow-up was not associated with visual field progression in the overall cohort or among glaucoma suspects or patients with mild glaucoma. However, among patients with moderate or severe disease, delays exceeding 60 days were associated with significantly greater odds of progression than delays of less than 30 days. Extended follow-up intervals may be appropriate for many glaucoma patients, particularly those with stable, mild disease, but close monitoring remains critical for more advanced cases.

Investigative Ophthalmology and Visual Science  

Can systemic inflammatory markers predict ocular aging?

The eye may be immune-privileged, but systemic inflammation may still find a way in. Systemic inflammation has long been implicated in many chronic diseases, although its role in ocular disease is less clear due to the eye’s immune-privileged state. Recent evidence suggests that low-grade systemic inflammation may contribute to the development of several age-related eye diseases. In this population-based prospective cohort study, researchers used data from 415,599 participants in the UK Biobank to investigate whether systemic immune-inflammatory biomarkers were associated with cataract formation, primary open-angle glaucoma (POAG), age-related macular degeneration (AMD), and diabetic retinopathy (DR). Inflammatory burden was assessed using the systemic immune-inflammation index (SII) and low-grade inflammation score (INFLA-score), based on hematologic and inflammatory serum markers. Both SII and INFLA-scores demonstrated significant, dose-dependent relationships with increased incidence of cataract formation, POAG, AMD, and DR. Cataract and POAG exhibited J-shaped relationships, whereas AMD and DR demonstrated linear relationships. Elevated inflammatory markers were also associated with thinner retinal layers on OCT. These findings suggest that systemic inflammation may play a broader role in age-related ocular disease than previously appreciated and raise the possibility of anti-inflammatory therapies to slow progression. 

Nature Medicine

A light switch for blindness? Photoswitch therapy shows early promise in retinitis pigmentosa

Turns out retinal ganglion cells might just need a little “light switch” to get back in the game. Retinitis pigmentosa (RP) is a progressive inherited retinal disease that leads to severe vision loss due to photoreceptor degeneration. Because RP is caused by hundreds of different mutations, there is growing interest in “gene-agnostic” therapies that target surviving inner retinal cells regardless of the underlying genetic defect. ABACUS-1 is a phase 1, open-label, non-randomized, dose-escalation trial that administered intravitreal injections of KIO-301, a photoswitch molecule designed to make surviving retinal ganglion cells responsive to light, into 12 eyes of 6 participants with advanced RP. The primary safety endpoint of this trial was successfully met, with KIO-301 demonstrating a favorable safety profile with no serious adverse events, dose-limiting toxicities, or intraocular inflammation. Exploratory testing captured transient improvements in light perception, functional vision, and visually evoked cortical activation in a subset of participants. Functional vision improvements in tasks such as walking direction peaked near day 15, while functional MRI scans showed stimulus-associated visual cortex activation within 2-3 days of dosing. Although limited by its open-label design and small cohort, this study establishes the feasibility of intravitreal photoswitch therapy and provides a foundation for future trials to evaluate clinical efficacy.

IL-6 inhibition in uveitic macular edema: insights from the DOVETAIL trial

UME may be entering its low-cortisol era. Uveitic macular edema (UME) is a leading cause of vision loss in patients with uveitis and remains challenging to manage with corticosteroids alone. Current therapies, including intravitreal corticosteroid injections, are limited by complications such as cataract formation, elevated intraocular pressure, and the need for repeated treatment. Although biologic therapies have emerged as steroid-sparing options, the only approved biologic for noninfectious uveitis, adalimumab, requires chronic systemic administration, has limited efficacy in refractory UME, and carries the risk of systemic adverse effects. The DOVETAIL trial is a phase 1 multicenter, nonrandomized, multiple-ascending-dose study investigating intravitreal Vamikibart, a novel IL-6 inhibitor, for UME secondary to noninfectious uveitis. Thirty-seven patients were enrolled across three dose cohorts (0.25 mg, 1 mg, and 2.5 mg). At week 12, patients demonstrated a mean improvement in best-corrected visual acuity of +9.9 letters and a mean reduction in central subfield thickness of 161.5 μm. Vamikibart demonstrated a favorable safety profile with no major dose-limiting toxicities, supporting IL-6 inhibition as a promising future steroid-sparing therapeutic strategy for noninfectious UME.

The Lancet Digital Health

Can AI predict who will benefit from anti-VEGF for wet AMD?

Treatment response in neovascular age-related macular degeneration (nAMD) can be difficult to predict, even though repeated injections carry major financial and procedural burden. In this prospective multicenter study across 18 tertiary hospitals in China, investigators developed the KongMing Model, a lesion-aware transformer-based deep learning system trained on pretreatment optical coherence tomography (OCT) images to predict both functional and anatomic response to anti-vascular endothelial growth factor (anti-VEGF) therapy under a 3+PRN regimen. The model generated three clinically relevant forecasts: response after a single injection, after the initial three loading injections, and at 1 year. KongMing showed excellent performance for predicting best-corrected visual acuity (BCVA) change, with AUCs of 0.948, 0.972, and 0.989 in the internal test set and 0.941, 0.964, and 0.979 in the external test set across those same timepoints, while also outperforming ophthalmologists in head-to-head comparison. The model also predicted post-treatment BCVA values with low mean absolute error (~0.05) and generated post-treatment OCT images that closely resembled true scans. Overall, this study suggests AI may help personalize anti-VEGF counseling and treatment planning in nAMD by forecasting both visual and structural outcomes before therapy begins. 

Tolerating Subretinal Fluid (FLUID)

Might perfect be the enemy of good…when it comes to subretinal fluid retention. In the 2019 FLUID Study, visual acuity was assessed in patients with neovascular age-related macular degeneration (nAMD) previously randomized to treatment with monthly ranibizumab 0.5mg until resolution of intraretinal fluid (IRF) only (tolerating 200 microns of SRF) (n=175) versus complete resolution of both IRF and subretinal fluid (SRF) (n=174) before extending treatment intervals.

Key Points:  

• Of the 279 (79.9%) patients completing 24-month follow-up, there was no statistical difference in visual acuity outcomes between the two groups (P=0.99)
• Participants in group that allowed residual SRF received fewer ranibizumab injections over 24 months (P = 0.001) and significantly more participants with residual SRF extended to and maintained 12-week treatment intervals (P = 0.005)

Overall, the FLUID study is a landmark study because it showed that incomplete subretinal fluid resolution did not create significant differences in long-term visual acuity in patients with nAMD and demonstrated the need for fewer injections with longer maintenance intervals in its treatment.