In this week’s issue

• Multicenter study shows anterior chamber liquid biopsy is highly safe for molecular diagnostics in pediatric retinoblastoma patients.
• Higher dietary nitrate intake was linked to lower progression risk of late AMD, but associations disappeared after adjusting for Mediterranean diet patterns.
• Virulent, nonsurface commensal pathogens in postprocedure endophthalmitis are linked to worse visual outcomes and higher complication rates than less virulent organisms.
• Hyperspectral autofluorescence imaging identified a novel emission spectrum specific to drusen and sub-RPE deposits in AMD donor eyes.

Spotify Link:

https://open.spotify.com/episode/5eO5pWnueB3tcHu20MbHrp?si=BO6LLb4vQ0WoepnHOOvxdQ

Ophthalmology 

Safety of aqueous humor liquid biopsy in retinoblastoma

Safe diagnostic procedure or risky jab? Aqueous humor (AH) liquid biopsy can provide invaluable information regarding the molecular profile of a child’s tumor in cases of suspected pediatric retinoblastoma. However, many clinicians are reluctant to perform this procedure due to a perceived risk of tumor seeding. This study retrospectively reviewed over 1,200 anterior chamber paracenteses performed as part of aqueous humor (AH) liquid biopsy in children with retinoblastoma across multiple centers to evaluate the safety and tolerability of obtaining AH for molecular analysis. AH liquid biopsy via anterior chamber paracentesis was generally safe and well-tolerated with a low rate (0.08%) of significant complications, supporting its use as a minimally invasive diagnostic and monitoring tool in retinoblastoma care. This large cohort provides real-world evidence that AH liquid biopsy can be implemented safely in pediatric patients with intraocular tumors, potentially aiding precision oncology and management decisions without substantially increasing procedural risk.

JAMA Ophthalmology

Can leafy greens protect against macular degeneration?

Spinach for sight? Age-related macular degeneration (AMD) is a leading cause of vision loss, and lifestyle factors such as diet may influence how quickly the disease progresses. Nitrates, found in leafy green vegetables, can increase nitric oxide levels and affect vascular and inflammatory pathways in the retina, raising the question of whether nitrate intake might help slow AMD progression. This cohort study analyzed data from the AREDS and AREDS2 trials, including 7,788 participants followed for a median of ~10 years. Researchers estimated dietary nitrate intake using food frequency questionnaires and examined whether higher intake was associated with progression to late AMD, geographic atrophy (GA), or neovascular AMD. Participants with the highest nitrate intake had a lower risk of progression to late AMD (HR ~0.77) and reduced risks of GA and neovascular AMD compared with those with the lowest intake. However, nitrate intake strongly correlated with adherence to a Mediterranean-style diet and after adjusting for this dietary pattern, the protective association disappeared. While higher nitrate intake seemed beneficial at first glance, the effect likely reflects overall healthy, plant-rich diets rather than nitrate alone. For clinicians and patients, the message remains simple: encouraging vegetable-rich dietary patterns may be more meaningful than focusing on a single nutrient.

American Journal of Ophthalmology (AJO)

Impact of causal organism on visual outcomes in endophthalmitis 

How bad is it, doc? Well, it depends. Endophthalmitis is the feared complication of intraocular procedures, particularly cataract surgery and intravitreal injections. It causes severe vision loss or blindness in 30-50% of cases. Depending on visual acuity at presentation, patients undergo either a tap and injection of antibiotics or pars plana vitrectomy. This multicenter study offers a potential new method to risk stratify endophthalmitis patients by causal organism rather than by presenting visual acuity. A total of 240 patients with acute endophthalmitis were studied, and causal bacteria were stratified by their status as commensal bacteria (coagulase-negative Staphylococcus species) versus nonsurface commensals (Streptococcus spp, Enterococcus spp, and other less common species) to serve as a proxy for virulence. Nonsurface commensals caused significantly worse final visual outcomes compared to surface commensals. Highly virulent organisms were also independently associated with higher rates of a third surgical intervention, phthisis, and need for enucleation/evisceration. These findings together highlight the significant difference in outcomes of this devastating complication based on causal organisms and the potential to more accurately prognosticate using crucial culture data. 

Investigative Ophthalmology & Visual Science (IOVS) 

Can “color fingerprints” of the retina reveal early AMD risk?

Turns out drusen might have unique spectral signatures hiding in plain sight. Age-related macular degeneration (AMD) is characterized by the accumulation of drusen, lipid- and protein-rich deposits beneath the retinal pigment epithelium. Clinically, drusen size and morphology are used to stage disease risk, but these features may not capture the underlying biochemical differences that drive AMD progression. Hyperspectral imaging (HSI), which captures detailed spectral information across many wavelengths, offers a potential way to identify subtle molecular variations in retinal deposits. Understanding whether drusen have distinct spectral profiles could improve early detection and classification of AMD. Researchers applied hyperspectral imaging to retinal tissue containing drusen, analyzing spectral signatures across multiple wavelengths and using computational classification methods to differentiate drusen types and surrounding retinal structures. Drusen displayed distinct hyperspectral signatures that differed from surrounding retinal tissues, allowing automated classification based on spectral characteristics. Spectral variability among drusen suggested compositional differences that are not detectable using standard fundus imaging, indicating that HSI can identify biochemical heterogeneity within AMD lesions. Hyperspectral imaging may provide a powerful new tool for noninvasively characterizing drusen composition and improving AMD risk stratification, potentially enabling earlier detection of disease changes before structural damage becomes apparent.

Ophthalmology Glaucoma

Corneal transplantation risk after glaucoma surgery: Tubes vs. trabs

How does glaucoma surgery type affect long-term corneal health? This IRIS Registry study evaluated 246,521 eyes undergoing traditional incisional glaucoma surgery. Corneal transplant occurred in 0.8% of trabeculectomy eyes, 3.0% of tube shunt eyes, and 5.0% of eyes receiving both. The mean time to transplant was shorter after tube shunt (2.5 years) vs. trabeculectomy (3.8 years). Adjusted analyses showed 4-6 times higher likelihood of corneal transplantation after tube shunts or combined surgery vs. trabeculectomy alone. Eyes with pre-existing corneal disease (bullous keratopathy, Fuchs dystrophy) or pseudophakia were at higher risk for corneal transplantation, whereas cataract surgery performed after glaucoma surgery was associated with a lower risk. Findings highlight potential chronic corneal compromise from tube shunts and the importance of corneal health in surgical planning.

Ophthalmology Retina

Dye-free angiography? AI generates UWF-FA from fundus photos

Ultra-widefield fluorescein angiography (UWF-FA) improves detection of diabetic retinopathy (DR) lesions but requires IV dye and carries potential adverse effects. In this cross-sectional study, investigators trained a modified pix2pixHD generative adversarial network using paired ultra-widefield color fundus photographs (UWF-CFP) and angiograms from 1,263 patients with DR to generate early-, mid-, and late-phase UWF-FA images. Incorporating AI-generated UWF-FA images into DR grading significantly improved performance, increasing AUROC from 0.869 with CFP alone to 0.904 when all generated FA phases were included. Ophthalmologists also mistook generated images for real angiograms in up to 76% of cases, suggesting high realism. These findings highlight the potential of generative AI to enable noninvasive angiography and improve DR screening workflows. 

Central Vein Occlusion Study (CVOS) - 1995

Does prophylactic photocoagulation help central retinal vein occlusion (CRVO) outcomes? This phase 3 randomized control trial in 1995 analyzed patients who had CRVO within the last year and split them into Group N (181 patients with nonperfused CRVO with no neovascularization) and Group M (151 patients with 20/50 or worse visual acuity and macular edema secondary to CRVO). The primary outcome for Group N was regression of the development of neovascularization after prophylactic pan-retinal photocoagulation (PRP). The primary outcome for Group M was visual acuity after macular grid laser therapy at 3 years.

Key Points

• Group N: Prophylactic PRP reduced proportion of patients who developed iris or angle neovascularization, but this difference was not statistically significant (35% vs. 20%, OR 0.6, P = 0.17) after adjusting for baseline characteristics
• Group N: Iris and angle neovascularization was more successfully treated by PRP in patients who had not had prophylactic PRP (56% vs. 22%, OR 4.5, P = 0.02)
• Group M: There was no statistically significant difference in visual acuity in those who received grid laser versus those who received no treatment at 3 years.

Overall, the CVOS study is a landmark study because it did not support prophylactic photocoagulation being utilized for the treatment of CRVO. While treatment regimens have changed since the development of Anti-VEGF agents and improved clinical imaging (OCT), the CVOS remains one of the important foundational studies in the field.