Current Issue

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In this week’s issue

• GLP-1 agonists and SGLT-2 inhibitors, commonly used for weight loss and type 2 diabetes treatment, may be associated with increased risk of developing NAION.
• Radiomics analysis of OCT imaging with machine learning demonstrates accuracy in identifying corneal features in the early stages of keratoconus.
• Glaucoma patients who sleep with 2 pillows at night may have increased nocturnal IOP, worse IOP fluctuations, and lower ocular perfusion pressure.

Spotify Link:

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

JAMA Ophthalmology

New onset NAION in US veterans with type 2 diabetes

Weight loss at a cost. Glucagon-like peptide-1 receptor agonists (GLP1RAs) are generally safe when used for weight loss and type 2 diabetes treatment, but new evidence suggests there may be an association between the use of GLP1RAs and new-onset non-arteritic ischemic optic neuropathy (NAION). This observational study used data from the Veteran’s Association (VA) from 2018 to 2025 to emulate heterogeneous data sources. The goal was to determine the incidence of NAION in patients initiating a GLP1RA (semaglutide) and an SGLT2 inhibitor, the most common second-line therapy for type 2 diabetes. A total of 102,361 veterans met inclusion criteria for the study. Of these, 11,478 veterans initiated semaglutide and 90,883 initiated an SGLT2 inhibitor. Over the course of the study, 173 NAION events occurred. Semaglutide was found to have a 2-fold increased risk of leading to NAION over SGLT2 inhibitors. Though the risk is low, clinicians should counsel patients on the risk of developing NAION upon initiation of semaglutide.

American Journal of Ophthalmology (AJO)

Detection of forme fruste keratoconus using OCT radiomics

Can machine learning detect subclinical keratoconus before we can? Forme fruste keratoconus (FFKC), the earliest subclinical stage of the disease, is challenging to diagnose because it lacks obvious topographic abnormalities or clinical manifestations. Conventional diagnostic methods cannot fully capture subtle microstructural alterations in stromal collagen architecture. Optical coherence tomography (OCT) is a widely available, non-invasive modality that can identify these structural features. This cross-sectional study evaluated an OCT-based radiomics approach that quantified texture features extracted from OCT images and applied machine learning models to differentiate FFKC from normal corneas. A total of 307 eyes (234 normal, 73 FFKC) were analyzed using Random Forest, C5.0, and XGBoost machine learning classifiers. Of the 3,752 identified features per eye, 41 were retained to optimize prediction accuracy. All machine learning models showed strong diagnostic performance (AUC > 0.92), with XGBoost achieving the highest performance (AUC 0.93, sensitivity 85.7%, specificity 97.8%, and accuracy 95%). Most of the discriminative features were localized to the inferotemporal cornea. Radiomics analysis of corneal OCT images combined with machine learning may serve as a potential imaging biomarker for accurate detection of FFKC using a single imaging device.

British Journal of Ophthalmology

Does sleeping with two pillows raise IOP in glaucoma?

Can a common bedtime habit influence nocturnal IOP? Body posture is known to affect intraocular pressure (IOP), and positional modification has been proposed as a simple adjunct to glaucoma management. In this prospective study of 144 patients with glaucoma undergoing 24-hour IOP monitoring, investigators assessed the effect of supine position with a “high-pillow” posture (head elevation 20-35° using two regular pillows) on IOP. Contrary to the hypothesis that head elevation might reduce IOP, the high-pillow position was associated with significantly higher nocturnal IOP (+1.61 ± 1.31 mm Hg), greater 24-hour IOP fluctuation, and reduced ocular perfusion pressure. Nearly two-thirds of patients demonstrated IOP elevation in the high-pillow position. Greater postural IOP changes were observed in younger patients and in those with primary open-angle glaucoma (POAG), with thicker central corneal thickness and POAG independently predicting larger IOP shifts. Complementary ultrasonography in healthy volunteers demonstrated significant compression of the internal and external jugular veins in the high-pillow position, suggesting there may be a mechanistic link between neck flexion, impaired venous outflow, and subsequently elevated IOP. This study demonstrates that the commonly adopted high-pillow sleeping position may adversely affect nocturnal IOP control and instead glaucoma patients should be counseled to avoid neck-flexed positions for long-term IOP management.

Translational Vision Sciences and Technology

Assessment of anterior uveitis through AS-OCT and AI

AI to detect inflammation. Anterior uveitis is the most common form of intraocular inflammation and a major contributor to vision loss through complications such as cataract, glaucoma, and macular edema. Accurate assessment of inflammatory activity is essential for guiding treatment, yet current clinical grading systems (e.g., SUN criteria) rely on subjective slit-lamp examination and are prone to inter-observer variability, even among experienced uveitis specialists. This prospective study investigated the use of artificial intelligence-assisted anterior-segment optical coherence tomography (AS-OCT) to objectively quantify inflammation in anterior uveitis among 32 eyes of 19 patients. The authors developed an automated image analysis pipeline that segmented the anterior chamber and identified hyper-reflective particles corresponding to inflammatory cells. The AI-based particle counts showed strong agreement with expert clinical SUN grading (Spearman ρ = 0.7077) and manual cell counts (Pearson's r = 0.9948) demonstrating high correlation with SUN anterior chamber cell scores. AI-based image analysis demonstrates high diagnostic accuracy and an opportunity for objective assessment independent of clinician experience to detect longitudinal changes over time.

Journal: American Journal of Ophthalmology

Clinical and systemic risk factors predict early progression in NAION

Who gets worse after NAION? Predicting early progression in acute nonarteritic anterior ischemic optic neuropathy (NAION) represents a significant clinical challenge. In this secondary analysis of 589 placebo-treated eyes from the multicenter QRK207 trial, the investigators assessed whether structured clinical and systemic variables alone could predict early visual decline using machine-learning models. Visual worsening was defined as ≥10- or ≥15-letter ETDRS loss or deterioration in visual field average total deviation, with performance evaluated across logistic regression and tree-based classifiers. Model discrimination was modest (AUROC 0.59-0.77), suggesting that routinely collected clinical features provide limited predictive power. Early progression was associated with fellow-eye NAION, obstructive sleep apnea, and higher diastolic blood pressure, whereas later decline reflected markers of metabolic and vascular stress, including elevated LDH, triglycerides, BMI, and blood pressure. Preserved RNFL thickness, normal renal indices, and diabetes medication use were linked to lower risk. While clinical variables identify biologically plausible risk patterns, meaningful improvement in prediction will likely require richer ophthalmic biomarkers and longitudinal, multimodal modeling approaches.

The Glaucoma Laser Trial (GLT) - 1990

Nowadays we can’t imagine a world without lasers in glaucoma! Published in 1990, the Glaucoma Laser Trial (GLT) sought to determine the safety and efficacy of Argon Laser Trabeculoplasty (ALT) compared to topical medications (timolol drops) as first-line treatment of primary open-angle glaucoma (POAG). In this multicenter RCT from the early 1990s, 271 patients were included, and the two eyes of each patient were randomized into two groups: ALT first (LF, n = 271) or timolol maleate 5% first (MF, n = 271).

Key Points

• Compared to MF eyes, LF eyes resulted in lower IOP and less reliance on ocular antihypertensive medications at 2-year follow-up
• Visual acuity and visual fields were stable at 2-year follow-up in both groups
• A 3.5-year follow-up study found slightly less deterioration in visual fields of LF eyes than in MF eyes

GLT is a landmark study that challenged the traditional paradigm of maximizing medical therapy before utilizing laser treatment. This study found ALT to be effective and safe in patients with POAG and comparable to medical therapy overall. However, despite these findings, ALT was rarely used as a first-line therapy due to the adoption of more effective glaucoma medications (prostaglandin analogues) and due its risk of trabecular meshwork scarring over multiple treatments. ALT paved the way for the introduction of newer forms of laser trabeculoplasty, such as selective laser trabeculoplasty (SLT).