Current Issue

---

Join The Lens!

Are you interested in being part of The Lens team? Applications are now open and will be due on January 23, 2026 at 11:59 EST. Please click this link to learn more about how you can contribute to The Lens and to apply by the deadline!

In this week’s issue

• In preterm infants, early postnatal increases in FGF-21 were associated with a higher risk of severe retinopathy of prematurity
• Immune checkpoint inhibitor therapy in cancer patients is associated with a reduced risk of developing non-neovascular AMD
• AI-based OCT fluid quantification (IRF/SRF) predicts 12-month visual outcomes in treatment-naïve DME treated with dexamethasone implants
• Automated ultra-widefield imaging hemorrhage analysis helps predict progression of NPDR to PDR

Spotify Link:

https://open.spotify.com/episode/2tIhrzALQ2ZWx6oBmOnBCH?si=50UvDQ3gSjuUji-MZDiHQQ

JAMA Ophthalmology

Proteomic profiles and ROP in extremely premature infants

This is not the food pyramid you’re thinking about. Retinopathy of prematurity (ROP) manifests after a preterm infant experiences metabolic and/or environmental stressors during the first weeks of life. ROP development is primarily influenced by the degree of prematurity, but can also be affected by suboptimal nutritional support, fluctuating oxygen levels, neonatal complications, and poor post-natal growth. In the Mega Donna Mega (MDM) trial, infants were given supplementation with arachidonic acid and docosahexaenoic acid. This showed a decrease in the incidence of ROP by 50%. In this post hoc analysis of the MDM trial, the longitudinal blood protein profiles of 177 preterm infants born before 28 weeks gestation, and their association with ROP, were examined. Half of the infants received enteral supplementation with AA/DHA (100/50 mg/kg per day) in addition to standard nutrition, from birth until their term-equivalent age. Blood samples were collected throughout the first month of life and examined for protein profiles. Of the 177 preterm infants, 50 developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life are associated with severe ROP. The most pronounced hormone with the development of ROP was fibroblast growth factor 21 (FGF-21), a metabolic stress-induced hormone. This study suggests that early nutritional intervention can prevent the development of severe ROP.

American Journal of Ophthalmology (AJO)

Can immune checkpoint inhibitors influence risk of AMD?

Cancer immunotherapy may do more than fight tumors. Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults and is recognized as a progressive disease influenced by chronic inflammation and immune dysregulation. While immune checkpoint inhibitors (ICIs) are widely used in oncology to promote T-cell activity, their long-term retinal effects remain poorly understood. Given growing evidence implicating adaptive immunity in AMD pathogenesis, there is a need to evaluate whether ICI therapy influences AMD risk or progression. This retrospective cohort study compared adults aged ≥60 years with cancer treated with ICIs to matched cancer controls without ICIs using the TriNetX Global Collaborative Network, with up to 5 years of follow-up (36,037 patients per group). ICI-treated patients had a significantly lower risk of developing non-neovascular AMD, with a hazard ratio (HR) of 0.77. This protective association was strongest for early AMD (HR 0.7) and early-intermediate AMD (HR 0.75). No significant association was observed between ICI use and neovascular AMD. Study limitations include the retrospective design and the potential for unmeasured confounders despite propensity score matching. ICI therapy was associated with a reduced incidence of non-neovascular AMD in older adults with cancer, which highlights potential new avenues for immunologic research in AMD.

British Journal of Ophthalmology

Can AI predict visual outcomes in DME treated with steroids?

Turning OCT images into prognostic insight. For patients with diabetic macular edema (DME), central retinal thickness has long been the mainstay anatomical marker guiding treatment decisions. Advances in artificial intelligence (AI) allow quantitative assessment of retinal fluid compartments, offering the potential for more meaningful prognostication. In this multicenter, retrospective study using a national DME dataset with associated optical coherence tomography (OCT) images, 101 treatment-naïve DME eyes treated with dexamethasone implants underwent AI-based quantification of intraretinal fluid (IRF) and subretinal fluid (SRF) from baseline OCT scans, with outcomes assessed over 12 months. Higher baseline SRF volume was associated with worse visual acuity at 12 months (-12.5 letters), while persistent IRF, particularly at 3 months, was associated with poorer visual outcomes at 12 months (-13.7 letters). Notably, each 100nL reduction in IRF at 3 months was associated with a 1.54 letter gain in VA, however, at 12 months, no fluid compartment showed significant association. These findings suggest that AI-driven fluid quantification can potentially identify prognostically meaningful biomarkers beyond retinal thickness, supporting earlier, more personalized treatment strategies in DME managed with dexamethasone implants.

Eye

AI-based prediction of progression to PDR

Can AI see the future of diabetic retinopathy progression? Progression from non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) remains a major cause of vision loss worldwide. Traditional grading for diabetic retinopathy severity relies on manual assessment of lesions within limited retinal fields, which is time-intensive and poorly scalable. Thus, automated approaches, such as ultra-widefield (UWF) imaging and AI-based lesion detection, may facilitate disease progression. This retrospective study analyzed 63 eyes with NPDR using UWF pseudocolor images at baseline and one-year follow-up. Retinal hemorrhages were quantified manually by expert graders and automatically using the EyeRead deep-learning algorithm. Hemorrhage number, area, and distance from the optic nerve head were measured. Automated measurements detected fewer hemorrhages than manual grading but showed strong correlations (r = 0.5-0.96). Both methods found that larger hemorrhage distance from the optic nerve independently predicted progression to PDR. Despite under-detecting lesion burden, automated hemorrhage quantification proves to be an evolving approach to help identify NPDR patients at higher risk of progression to PDR.

Ophthalmic Plastic and Reconstructive Surgery

Does short-term periocular triamcinolone 0.025% elevate IOP?

Can brief periocular steroid use increase intraocular pressure? Steroids are notoriously known for elevating intraocular pressure (IOP), raising concern even when used just around the eye. A retrospective review at a single specialty oculoplastic practice was conducted to evaluate short-term periocular steroid use and the risk of developing elevated IOPs. 62 patients (120 eyes) with baseline and follow-up IOP measurements were included in the study with analysis including associations with age, dosing frequency, procedure type, application site, and concomitant steroid or 5-fluorouracil use. Mean IOP remained unchanged overall (14.35 vs 14.32 mmHg), with no significant increases across most variables. Bilateral upper eyelid application was associated with a small but statistically significant increase of 1.7 mmHg, which remained within normal limits. Overall, short-term periocular 0.025% triamcinolone was not associated with clinically meaningful IOP elevation, supporting its safety in oculoplastic care.

Early Treatment Diabetic Retinopathy Study (ETDRS) - 1991

Ever wonder where those famous “EDTRS letters” come from? The Early Treatment Diabetic Retinopathy Study (ETDRS) explored the role of focal laser coagulation, panretinal photocoagulation (PRP), and aspirin use for the treatment of non-proliferative diabetic retinopathy (NPDR) and early proliferative diabetic retinopathy (PDR). A total of 3,711 patients were included in ETDRS and randomized into two cohorts according to aspirin use (aspirin, 650 mg/day, n = 1,856; placebo, n = 1855). For each patient, each eye was assigned to early or deferred photocoagulation. The cohort of early photocoagulation eyes was further subdivided according to timing of focal and panretinal/scatter photocoagulation. Photocoagulation in deferred eyes was initiated upon detection of high-risk PDR.

Key Points

• Defined grading criteria for NPDR (see linked study with images)
• Early focal photocoagulation reduced the risk of vision loss from diabetic macular edema (ETDRS Report Number 1, 9)
• PRP decreased the risk of severe vision loss in patients with proliferative or severe non-proliferative diabetic retinopathy, but should be withheld in those with moderate or mild non-proliferative diabetic retinopathy due to adverse effects on visual field and acuity (ETDRS Report Number 9)
• Aspirin did not alter the disease course of diabetic retinopathy. Furthermore, aspirin use was not associated with adverse ocular events, including vitreous or preretinal hemorrhage. (ETDRS Report Number 8, 19, 20)

Overall, the ETDRS demonstrated that early focal photocoagulation can avert vision loss related to diabetic macular edema. PRP is beneficial for patients with PDR or severe NPDR, but the risks outweigh the benefits for patients with mild or moderate NPDR. This study further laid the groundwork for many future Diabetic Retinopathy and other retina studies.