Audio link: 

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

In this week’s issue

• Acoltremon, a selective TRPM8 (cold-sensing receptor) agonist, increased natural tear production in patients with moderate-to-severe dry eye disease in two phase 3 trials (COMET-2 and COMET-3).
• Handheld OCT appears to be less stressful than traditional binocular indirect ophthalmoscopy for infants undergoing ROP screening. 
• In a retrospective analysis of patients with optic disc edema, researchers found that outpatient stat MRI pathways reduced cost and visit duration compared to emergency-room-based stat MRI pathways.  
• In a retrospective TriNetX cohort study, researchers found that calcium channel blockers were associated with a higher risk of progression of primary open-angle glaucoma. 

Ophthalmology

A “cool” new way to treat dry eye

Can a “cooling” signal help dry-eye patients produce more tears? Dry eye disease (DED) is common, burdensome, and often difficult to treat. TRPM8, the cold-sensing receptor pathway associated with the cooling sensation of menthol, helps regulate basal tear production through corneal cold thermoreceptors. Acoltremon is a selective TRPM8 agonist that stimulates this pathway and increases natural tear production. In the phase 3 COMET-2 and COMET-3 trials, 931 adults with moderate-to-severe DED were randomized to acoltremon or vehicle twice daily for 90 days. Acoltremon met the primary endpoint in both studies, with significantly more patients achieving a ≥10-mm increase in Schirmer score by day 14. Tear production improved as early as day 1 and persisted through day 90, with accompanying improvements in ocular staining. Symptoms generally improved as well. The main adverse event reported was mild burning or stinging with drop use. These findings suggest that acoltremon may add a new treatment approach for DED via tear stimulation.

JAMA Ophthalmology 

Infant stress during handheld OCTs vs. contact fundus photography 

The kids are stressing out! The number of infants needing retinopathy of prematurity (ROP) exams in the US grows each year. Traditional exams include contact fundus photography using binocular indirect ophthalmoscopy (BIO), which can cause significant discomfort in infants. Handheld optical coherence tomography (OCT) is thought to be less stressful, but no studies have directly compared behavioral and physiological responses between handheld and conventional OCT. A prospective cohort study was done with 59 infants over 399 imaging sessions. Compared with fundus photography, OCT shows less change in cry score, facial expression score, and heart rate from baseline through imaging and into the post-imaging period. Additionally, of the 32 total adverse events, 26 occurred during or after fundus photography, including tachycardia, bradycardia, hypoxia, and emesis. These results suggest that handheld OCT was less stressful for infants and resulted in fewer adverse events than BIO. The role of handheld OCTs in ROP exams warrants further investigation to establish their feasibility.

American Journal of Ophthalmology 

Cutting costs without cutting corners: rethinking MRI pathways for optic disc edema

Can urgent neuroimaging be faster and cheaper without compromising care? Optic disc edema refers to swelling of the optic nerve head. It serves as one of the most important "red flags" in ophthalmology because it can signal life-threatening intracranial pathology. Clinicians rely on timely neuroimaging as an essential part of the workup for many cases of optic disc edema. In this retrospective analysis of 129 patients with optic disc edema, researchers used a time-driven activity-based costing (TDABC) approach to map workflows and calculate costs across all personnel, facilities, equipment, and consumables. Patients underwent imaging in the emergency department (ED) or via an outpatient STAT pathway between November 2018 and February 2024. Primary outcomes included total cost and visit duration. The STAT MRI pathway significantly reduced costs and improved efficiency compared with conventional ED-based neuroimaging, resulting in a 20% cost reduction and a 70% shorter visit duration. The outpatient STAT pathway offers a cost- and time-efficient alternative to ED-based neuroimaging for select patients with optic disc edema, while also alleviating ED burden.

Investigative Ophthalmology and Visual Science  

Could calcium channel blockers raise the risk of glaucoma progression? 

A common blood pressure medication class may put glaucoma care under a little more pressure. Calcium channel blockers (CCBs) are commonly prescribed for hypertension, angina, and coronary artery disease, but their relationship with glaucoma progression remains uncertain. CCBs are broadly divided into dihydropyridine CCBs (dCCBs), which primarily act as peripheral vasodilators, and nondihydropyridine CCBs (ndCCBs), which more strongly affect cardiac conduction. This study investigated whether either subclass was associated with progression from mild-to-moderate primary open-angle glaucoma (POAG) to severe disease. In this retrospective TriNetX cohort study, researchers compared patients with mild-to-moderate POAG taking dCCBs or ndCCBs with propensity-matched controls not taking CCBs, using progression to severe POAG as the primary outcome. After propensity matching, both dCCB and ndCCB use were associated with increased risk of progression to severe POAG compared with matched controls, with a stronger association seen among ndCCB users. Progression occurred in 3.5% of dCCB users versus 2.1% of matched controls, and 6.9% of ndCCB users versus 1.9% of matched controls. Although causality cannot be established, these findings suggest that patients with POAG taking CCBs may benefit from closer monitoring for early signs of progression.

AJO International

Saving sight in sickle cell disease 

Sub-Saharan Africa faces the greatest global burden of sickle cell disease. The HbSC variant is most often associated with sickle cell retinopathy. However, research on proliferative SCR (PSCR) among adults with the HbSC variant remains limited. This cross-sectional study included 184 patients with sickle cell disease (SCD) recruited from an outpatient clinic and a sickle cell registry at the main tertiary hospital in Kumasi, Ghana, from June 2023 to March 2024. In this cohort, 45.8% of HbSC and 19% of HbSS participants were diagnosed with PSCR, and 10.6% of HbSC participants received prophylactic laser treatment. The HbSC variant (OR=3.12) and age greater than 25 years (OR=2.73) were associated with increased odds of PSCR. Although this study examined patients already diagnosed and receiving specialized care, it highlights the need for early detection through newborn and school screenings, as well as for more research to improve understanding of PSCR management. 

Nature Medicine

The eye is the window to the systemic disease 

Can retina AI be used to detect systemic disease? Noninvasive low-cost approaches, such as retinal image-based detection, could improve access and reduce healthcare inequities. Investigators developed Reti-Pioneer, a machine learning model, and trained it on 107,730 color fundus photos from 53,865 individuals in hospital and community-based cohorts across China, the UK, and Singapore. Reti-Pioneer accurately detected six systemic diseases, as measured by the Area Under the Receiver Operating Characteristic Curve (AUROC), where values range from 0 to 1, with 1 indicating perfect discrimination. Performance was highest for type 2 diabetes (0.833) and gout (0.832), followed by osteoporosis (0.787), hypertension (0.740), hyperlipidemia (0.736), and thyroid disease (0.699). Reti-Pioneer improved the diagnostic accuracy of experienced retinal specialists in a real-world blinded reader study, improving diagnostic accuracy by 7 to 28 percentage points. Retinal image screening may very well streamline clinical workflows and expand healthcare access in low-resource settings.

The Baltimore Eye Study (1991)

The Baltimore eye study determined the need for more screening methods to detect glaucoma. In the 1991 Baltimore eye study, researchers found that tonometry, optic nerve assessments, and medical history did not provide a reasonable balance of sensitivity and specificity to adequately screen a person for glaucoma.  

Key Points:  

• IOP is one of the strongest known risk factors for open-angle glaucoma, but the use of IOP as a referral criterion for glaucoma had little sensitivity 
• Measuring cup-to-disc ratios and neuroretinal rim width was also limited in its usefulness for screening glaucoma, showing a poor balance of sensitivity and specificity 

Overall, the Baltimore eye study is a landmark study because it showed that population-based glaucoma screening programs could not rely on tonometry alone to determine a person’s disease status. The effectiveness of past techniques was limited and new approaches to glaucoma screenings were encouraged.