Current Issue

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In this week’s issue

• The incidence of sports-related orbital fractures in the U.S. has remained stable over the past decade, with baseball, cycling, and softball as leading causes.
• GLP-1 receptor agonist use in non-diabetic patients who are overweight or obese reduces risk of developing dry AMD.
• Changes in cup-to-disc ratio alone are unreliable for predicting glaucoma progression.
• Metformin protects against developing primary open-angle glaucoma in adults aged 40 years and older with diabetes

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https://open.spotify.com/episode/4xP705A080rmz02ERM6ZC5?si=-Pt20_HlRhy-c0tfZAIe3Q

 Ophthalmology

Epidemiology of sports-related orbital fractures in the United States

Protect your orbit or get a fastball to fracture. Orbital fractures are common injuries in sports-related trauma and can cause significant ocular morbidity related to cosmetic deficits and possible long-term visual impairment. This retrospective cohort study included 1468 patients with sports-related orbital fractures from the National Electronic Injury Surveillance System (NEISS) from 2014 to 2023, corresponding to a nationwide estimate of 49,765 cases (95% CI, 47,219-52,311). Primary outcome measures included the nationwide incidence and mechanism of sports-related orbital fractures, including sport type, fracture site, and other associated ocular injuries. The mean age was 27.1 years old and 79% of the patients were male. Baseball (28.6%), cycling (23.1%), and softball (6.7%) were the most common sports-related causes of orbital trauma, with the orbital floor fractured in nearly 60% of cases. 14% of patients also developed non-fracture injuries such as eyelid lacerations, corneal abrasions, or hyphema. The incidence of sports-related orbital trauma has remained stable over the past decade, indicating that advances in safety have done little to limit risk of injury. This study highlights the vulnerability of the orbit to trauma and a further need for preventative measures for eye safety in sports.

American Journal of Ophthalmology (AJO)

Unreliability of cup to disc ratio in glaucoma progression

Just using cup to disc? Tsk tsk… Glaucoma is an optic neuropathy that is a leading cause of irreversible blindness worldwide. Glaucoma progression is monitored by assessing both functional damage with Standard Automated Perimetry (SAP) and structural damage with Optical Coherence Tomography (OCT). While cup-to-disc ratio (CDR) is a widely documented structural metric for glaucoma diagnosis, its utility in tracking disease progression is unclear. This retrospective cohort study whether longitudinal change in CDR could predict glaucomatous progression detected on concurrent OCT or SAP. The results demonstrated that longitudinal CDR changes had minimal accuracy in predicting glaucoma progression, with the predictive accuracy of longitudinal change in CDR being similar to random selection. The AUC of CDR was 0.55 for identifying OCT progressors and 0.53 for identifying SAP progressors. Given the weak predictive value of CDR, the study highlights the need for ophthalmologists to rely on a combination of modalities, including optic nerve head examination and with ancillary testing like OCT and SAP, to effectively assess glaucomatous progression. 

JAMA Ophthalmology

Do GLP-1 weight-loss drugs protect against macular degeneration?

Weight-loss meds helping the macula? Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in older adults, with inflammation and metabolic dysfunction contributing to disease risk. GLP-1 receptor agonists (GLP-1RAs) like semaglutide are increasingly prescribed for weight loss, but their retinal effects, especially in non-diabetic populations, remain unclear. In this large retrospective cohort study of the TriNetX network, investigators evaluated whether GLP-1RAs reduce the risk of developing AMD in individuals diagnosed with overweight or obesity but without diabetes. After propensity matching, 45,704 patients prescribed semaglutide or liraglutide were compared with an equally sized cohort prescribed other weight-loss medications. GLP-1RA use was linked to a significantly lower risk of developing nonexudative AMD (83.5% lower at 5 years, 86.7% lower at 7 years, and 91.3% lower at 10 years). However, among patients who already had early AMD, GLP-1 drugs did not reduce progression to the more serious exudative form. These findings suggest GLP-1RAs may help protect against AMD onset in nondiabetic patients using these drugs for weight loss, supporting further trials investigating whether they could play a role in AMD prevention.

Investigative Ophthalmology & Visual Science (IOVS)  

Could a transcription factor hold the key to healing chemically injured corneas?

ZEB1: the cornea’s secret weapon against chemical assault. Mustard gas and related agents, such as nitrogen mustard (NM), can cause devastating corneal keratopathy marked by epithelial loss, inflammation, and scarring. While therapies like steroids or anti-VEGF agents help prevent corneal decompensation caused by this form of chemical injury, they carry side effects and do not address the underlying etiology of injury. In this in vivo laboratory study, researchers exposed murine corneas to NM in wild-type and ZEB1 heterozygous knockout mice. Corneal damage, cell death, proliferation, and stem cell activity were tracked using fluorescein staining, immunohistochemistry, TUNEL assays, and gene expression analysis. Wild-type mice experienced more acute corneal injury and faster recovery, with ZEB1 promoting epithelial proliferation and maturation. ZEB1 knockdown delayed repair, reduced stem-like cell viability, and impaired epithelial regeneration. Targeting the ZEB1 pathway may open new therapeutic strategies for mustard gas keratopathy and severe ocular surface injuries.

Glacoma

BMJ Open Ophthalmology

Metformin and glaucoma: Can a diabetes drug protect vision?

Can metformin reduce the risk of developing primary open-angle glaucoma (POAG)? Using data from the All of Us Research Program, this retrospective cohort study evaluated 18,440 adults aged 40 years and older with diabetes and no prior diagnosis of POAG. Participants who used metformin had significantly lower odds of developing POAG (OR 0.33, 95% CI 0.21-0.50) and a reduced hazard over time (HR 0.38, 95% CI 0.29-0.51). Conversely, use of other diabetic medications was associated with higher odds of POAG (OR 2.39, 95% CI 1.48-3.90). The authors suggest that metformin may help protect the optic nerve by improving blood flow or supporting cell health through AMPK-related pathways. However, a cause-and-effect relationship cannot be determined because this was an observational study without details on dose, duration, or eye exam findings. Nevertheless, the study’s large and diverse cohort supports the observed association and highlights metformin as a promising target for future glaucoma research.

Journal: Ophthalmology

In-context learning for data-efficient DR detection via multimodal foundation models

This study explored whether multimodal foundation models can perform diabetic retinopathy (DR) detection using in-context learning (ICL), a method that allows models to adapt to new tasks from examples rather than retraining. Researchers evaluated Google Gemini 1.5 Pro using ICL on 516 color fundus photographs from the Indian Diabetic Retinopathy Image Dataset (IDRiD) and compared its performance to RETFound, a domain-specific model fine-tuned for retinal imaging. Gemini 1.5 Pro achieved an accuracy of 0.841 (95% CI: 0.803-0.879), F1 score of 0.877 (95% CI: 0.844-0.909), and an expected calibration error (ECE) of 0.129 (95% CI: 0.107-0.152) using optimized prompts and k-nearest-neighbor few-shot prompting. RETFound performed similarly, with an accuracy of 0.849 (95% CI: 0.813-0.885), F1 score of 0.883 (95% CI: 0.852-0.915), and lower ECE of 0.081 (95% CI: 0.066-0.097), indicating better calibration but no significant difference in accuracy or F1 score (P > 0.3). Both models demonstrated strong agreement (Cohen’s κ = 0.70). These results suggest that with well-engineered prompts and a small number of reference examples, multimodal models like Gemini can match the diagnostic performance of specialized models without retraining or large annotated datasets.

The Infant Aphakic Treatment Study (IATS) - 2014

Peekaboo! Eye See You! The Infant Aphakic Treatment Study (IATS) sought to assess visual outcomes in infants aged 1-6 months with a unilateral congenital cataract following cataract extraction surgery and either intraocular lens (IOL) implantation or left aphakic with contact lens usage. Patients received the same patching therapy and were followed up for up to 5 years.

Key Points

• Average visual acuity was not different between the two treatment groups.
• Risk of adverse events was higher in the IOL group (81%) than the contact lens group (56%).
• Need for additional intraoperative procedures was higher in the IOL group (72%) than the contact lens group (12%).
• The percentage of participants included in the adherence analyses did not differ by treatment group.

The IATS demonstrated the benefit of leaving babies aged 1-6 months with congenital cataract aphakic with a contact lens rather than pseudophakic. Many possible reasons may account for the observed benefits, including a less traumatic surgery with fewer reoperations and a better fitted IOL. Still, it is worthy to consider lOL placement to avoid amblyopia, especially in babies for whom placing contact lenses may be difficult.