Audio link: 

https://open.spotify.com/episode/2NFOOlNw7iVW9YMkAFmrnd?si=8938JWLZQfG_NFtXQ8zj4w

In this week’s issue

• Large language models perform well on ophthalmic knowledge-based assessments but are not ready for patient-facing care alone
• FOXC1 duplications play an exciting new role in understanding the genetics of JOAG
• Children with ROP requiring treatment may face an increased long-term risk of development of strabismus and benefit from increased ophthalmic surveillance
• A new study suggests the E2–ERβ–MMP2 signaling axis links estrogen imbalance to corneal collagen remodeling and biomechanical weakening in keratoconus pathology
• Intracanalicular dexamethasone inserts hold the potential to change pediatric post-operative care in ophthalmology 

Ophthalmology

Does AI actually know ophthalmology, or does it just sound like it does?

Confidence isn’t competence, and in ophthalmology, that distinction matters. Large language models (LLMs) are becoming increasingly accessible to both patients and clinicians, but their reliability in specialty medicine remains unclear. While prior studies have quantitatively evaluated LLM performance on ophthalmology knowledge-based questions, few have examined the quality of their free-text clinical reasoning, which is commonly how these tools are utilized in practice. In this cross-sectional study, researchers presented 120 AAO Basic and Clinical Science Course questions spanning 10 ophthalmic subspecialties to ChatGPT-4 and Gemini Pro 1.5. Three board-certified ophthalmologists then evaluated 50 prose responses from each model using a standardized rubric. ChatGPT-4 answered 82.5% of the multiple-choice questions correctly, outperforming the average physician score of 73% and Gemini's 49.2%. Incorrect reasoning was identified in 43% of ChatGPT-4 responses and 58% of Gemini responses. More than one-third of responses from both models also contained inaccuracies that could pose a risk of patient harm, including misdiagnoses that could lead to inappropriate surgery or delayed treatment of serious conditions. Although LLMs may perform well on knowledge-based assessments, physician oversight remains essential at this stage in the use of this technology in patient care.

JAMA Ophthalmology 

A “rare" gene duplication may play a underappreciated role in juvenile glaucoma 

Sometimes the missing diagnosis isn't a mutation—it's an extra copy. Juvenile open-angle glaucoma (JOAG) is a severe, early-onset form of glaucoma with a strong genetic basis. FOXC1 mutations and deletions are known causes of glaucoma, but the role of FOXC1 duplications remains unclear. Identifying overlooked genetic causes of JOAG could improve diagnostic yield and family screening guidance. In this retrospective genetic study, investigators analyzed two glaucoma cohorts from Australia/New Zealand and the United States and identified 20 affected individuals from 10 families carrying FOXC1 duplications. FOXC1 duplications accounted for 13.5% of genetically diagnosed JOAG cases in the Australian/New Zealand cohort and 9.5% in the US cohort, making this duplication one of the most common monogenic causes of JOAG. All genetically tested carriers in this study developed glaucoma, demonstrating a remarkably high disease penetrance. These findings potentially support the inclusion of routine copy-number FOXC1 variant testing in patients undergoing genetic evaluation for JOAG.

American Journal of Ophthalmology 

How does ROP severity relate to development of strabismus?

The consequences of retinopathy of prematurity may extend beyond the retina, with strabismus emerging as a common long-term complication. Retinopathy of prematurity (ROP) remains a major cause of childhood visual morbidity, yet its long-term effects on ocular alignment are not fully understood. In this large retrospective cohort study utilizing the TriNetX database, researchers evaluated the cumulative incidence of strabismus among children diagnosed with ROP and examined factors associated with the development of strabismus. The study included 27,720 children with ROP: 973 underwent treatment with laser photocoagulation and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, while 26,747 received no treatment. Using survival analysis and hazard models, investigators assessed the risk of strabismus over time. The cumulative incidence of strabismus was consistently higher among ROP-treated patients, reaching 34.78% at 5 years compared with 22.14% in untreated patients. Esodeviations were the most common subtype, occurring in 22.35% of ROP-treated patients and 11.87% of untreated patients. Treatment exposure was independently associated with an increased hazard of developing strabismus (adjusted hazard ratio [aHR] 1.58), while amblyopia (aHR 2.58) and nystagmus (aHR 1.76) were also independently associated with increased risk. These findings suggest that children with ROP requiring treatment face an increased long-term risk of development of strabismus and may benefit from ongoing ophthalmic surveillance to facilitate early detection and management of ocular misalignment.

Investigative Ophthalmology & Visual Science

Could estrogen be weakening the cornea in keratoconus?

Your hormones may be doing more than causing acne. Keratoconus (KC) is a progressive corneal ectasia characterized by stromal thinning, irregular astigmatism, and visual decline, but the biological factors underlying its age- and sex-associated patterns remain incompletely understood. In this study, researchers evaluated the role of sex hormones in 15 treatment-naïve KC patients and 12 matched controls, performed mechanistic experiments in human corneal stromal cells, and developed a high-estrogen rat model. KC patients exhibited significantly elevated plasma and tear estradiol levels, and tear estradiol correlated with steeper corneas, thinner corneal pachymetry, decreased visual acuity, and higher MMP2 levels. Further, high-estrogen exposure increased collagen-degrading MMP2 activity, reduced type I collagen expression, and weakened corneal biomechanics through an ERβ-dependent pathway. In vivo, estrogen-treated rats also developed thinner corneas, disrupted stromal collagen organization, and reduced corneal stiffness; mirroring key features of keratoconus. These findings identify an E2–ERβ–MMP2 signaling axis linking estrogen imbalance to corneal collagen remodeling and biomechanical weakening. This suggests that hormonal regulation may contribute to KC progression and could represent a future therapeutic target.

JAAPOS

Less drops, more recovery: Intracanalicular steroids in children following intraocular surgery

What if postoperative steroid drops weren't the default? Management of postoperative inflammation following intraocular surgery in both pediatric and adult patients often involves topical corticosteroid eye drops. However, adherence to these treatments can be challenging in children due to poor cooperation. Intracanalicular dexamethasone inserts have been studied in adult populations and offer a sustained-release alternative to traditional eyedrops; however, data regarding their efficacy in pediatric patients remains sparse. This retrospective chart review was conducted on pediatric patients who received a 0.4 mg dexamethasone intracanalicular insert following intraocular surgery. A total of 97 eyes received this insert following cataract extraction (n=68), secondary intraocular lens (IOL) implantation (n=27), and secondary membrane removal procedures (n=2). Following cataract surgery, 77% of eyes demonstrated no postoperative inflammation at 1 month, and rescue anti-inflammatory drops were required in 22% of cases. Additionally, following secondary IOL implantation, 92% of eyes demonstrated no postoperative inflammation at 1 month, and rescue anti-inflammatory drops were required in 20% of cases. This study showed that sustained-release intracanalicular dexamethasone inserts were associated with effective postoperative inflammation control and a favorable safety profile in pediatric patients. This technique may decrease dependence on postoperative eye drops and simplify perioperative care for children and their caregivers following intraocular surgery.

Eye

Can AI write the eye note for you? Not so fast.

Clinic notes may be tedious, but even the smallest mistake in documentation can have a big cost. Large language model-based scribing tools are increasingly marketed as a way to reduce documentation burden, but their performance in ophthalmology has remained unclear. In this cross-sectional comparative study, investigators tested six proprietary AI scribing tools using seven simulated ophthalmic encounters covering common conditions such as AMD, cataract, diabetic retinopathy, glaucoma, and retinal detachment. Consultant ophthalmologists graded the generated SOAP notes using the PDQI-9 framework and also assessed safety by identifying omissions, inaccuracies, and hallucinated content. Heidi AI achieved the highest overall documentation quality score (PDQI-9 38.5), with Whisper GPT-4o ranking second, but all six tools made clinically meaningful errors, most commonly omissions of disease severity, coexisting ocular disease, systemic comorbidities, and management details. Heidi AI also led on several automated text-generation metrics, but no tool was error-free. Overall, these results suggest AI scribes may help streamline ophthalmic documentation, yet human review remains essential before clinical implementation given the persistent risk of incomplete or inaccurate notes.

DRCR-S: PRP vs Ranibizumab for PDR - 2015

Can ranibizumab pull its weight? How does the monoclonal antibody compare to PRP? In the 2015 DRCR S study, patients with proliferative diabetic retinopathy were randomized to treatment with PRP (n = 191 eyes) and ranibizumab (n = 203 eyes) to determine if anti-VEGF therapy was a reasonable alternative to PRP.

Key Points:  

• Ranibizumab was non-inferior to PRP treatment for best corrected visual acuity at two-year follow-up (+2.8 letters vs. +0.2 letters, P = .11)
• Patients in the PRP group had more peripheral visual field loss than the Ranibizumab group (P < .001)
• Patients in the PRP group had more vitrectomies than patients in the Ranibizumab group (15% vs. 4%, P < .001)

Overall, the DRCR S study is a landmark study because it showed that ranibizumab was theoretically non-inferior to PRP for the treatment of PDR. In fact, the study showed that it might have superior visual outcomes (visual acuity and visual field measurements at 2 years). It is important to note that a key concern for long-term anti-VEGF therapy instead of PRP is that it requires high patient compliance and repeated interventions. As such, while the clinical study showed non-inferiority, clinicians must be wary about how these factors would impact the care of their patients and cost of care.