In this week’s issue

• Both high and low levels of HDL were associated with increased risk of AMD, though the mechanism for this remains unclear.
• A majority of ophthalmic subspecialists practice in urban areas, and this trend has increased over the last decade.
• Study compares 5 modern toric IOL formulas for cataract patients with astigmatism
• Systemic GLP-1 inhibitor treatment was found to reduce size and leakage of CNVM lesions in mouse models.

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Ophthalmology
High-density lipoproteins associated with AMD

Does "good" cholesterol have a dark side? While there is a growing body of literature implicating lipids in the pathogenesis of age-related macular degeneration (AMD), the association remains inconsistent. In this retrospective cross-sectional study, using data from 7,356 patients (2,328 with AMD and 5,028 healthy controls) in the NIH's All of Us research program, Chen et al. examined the association between clinical and genetically based factors of lipoprotein metabolism related to risk for AMD. On multivariable logistic regression, a U-shaped relationship was identified between HDL and AMD risk, where both low and high HDL levels were associated with increased risk (OR, 1.28 and 1.28, respectively). Statin use (OR 1.36) and HDL-related single-nucleotide polymorphisms (SNPs) were also associated with risk for AMD, with the novel SNP LPA (Lipoprotein[a]) (OR 1.37) emerging as a new potential genetic risk factor. This study sets the stage for future therapeutic approaches for lipid metabolism in AMD by identifying the pathogenic mechanism and implicating novel genetic risk factors.

JAMA Ophthalmology

Who’s doing eye surgery in rural America—and who isn’t?

Access to advanced eye care might just depend on your zip code. As America’s population continues to age, the need for general ophthalmic and also subspecialty care continues to rise. However, there’s a growing disparity of ophthalmologists located in urban counties compared to rural counties. This retrospective, cross-sectional study analyzed Medicare Fee-For-Service ophthalmological subspecialty surgical claims from 2012-2022 in patients 65 years and older to elucidate the geographic distribution of subspecialists. The study included a total of 13,526 ophthalmic subspecialists, comprising 2,540 cornea, 3,676 glaucoma, 1,951 oculoplastic, 4,123 retina, and 1,236 strabismus. Results showed that across all subspecialties, most surgeons practice in urban settings than rural settings (cornea difference, 87.0%; glaucoma difference, 81.4%; oculoplastics difference, 84.3%; retina difference, 86.0%; and strabismus difference 90.4%). A greater proportion of patients were located rurally compared with the proportion of surgeons practicing rurally. Of note, recent medical graduates within the last 10 years and females were also significantly less likely to practice rurally. This study reveals a growing rural-urban divide in access to subspecialized ophthalmic care, and underscores the need to develop incentives to increase rural subspecialty practice numbers.

American Journal of Ophthalmology
Which toric IOL formula cracks the code for astigmatism correction?

When it comes to correcting astigmatism, not all formulas are created equal! Astigmatism affects up to 40% of cataract patients; thus, accurate astigmatism correction drives advancements in toric intraocular lenses (IOL). Advanced toric IOL calculation formulas (Barrett, Emmetropia Verifying OPtical (EVO), Naeser/Savini combined with Hoffer QST, Kane, and Abulafia-Koch combined with Hill RBF) use data such as posterior corneal astigmatism and lens position estimation to improve refractive accuracy. This study aimed to directly compare the clinical outcomes of these 5 commonly used formulas to improve predictability in refractive results. This was a retrospective study of 146 cataract patients implanted with toric IOL using the Lenstar LS900 that evaluated mean absolute prediction error (MAE), centroid error, and proportion of eyes within a prediction error of ±0.50D and ±0.75 D, with subgroup analyses for with-the-rule, against-the-rule (ATR), and oblique astigmatism. All 5 calculation formulas showed comparable MAE; the proportion of eyes with prediction error <±0.50D was highest for EVO. In ATR astigmatism, Abulafia Koch combined with Hill RBF, EVO, and Naeser/Savini combined with Hoffer QST had lower MAEs than Barrett. All formulas showed excellent overall accuracy, with the EVO formula performing slightly better in ATR astigmatism, highlighting the importance of personalized formula selection based on clinical context.

Investigative Ophthalmology & Visual Science (IOVS)

Ozempic for the eyes? This study explored whether GLP-1 receptor (GLP-1R) agonist stimulation could suppress choroidal neovascularization (CNV) by reducing intraocular inflammation in a mouse model of neovascular AMD. CNV was induced via laser photocoagulation in C57BL/6J mice, followed by daily systemic liraglutide treatment. Treated mice showed significantly reduced CNV lesion size and vascular leakage on OCT and fluorescein angiography. To investigate the mechanism, researchers measured expression of inflammatory cytokines and quantified retinal immune cells. Liraglutide suppressed Il-1β, Ccl2, and Icam1 expression, and markedly reduced recruitment of Iba1-positive microglia/macrophages. These immune cells are known to drive retinal inflammation and neovascularization. The results suggest GLP-1R agonists, already approved for systemic use, may offer a new therapeutic approach for wet AMD by targeting both inflammation and angiogenesis.

Eye

Are intraocular lenses (IOLs) weighing down the planet?

Rethinking IOL packaging may help towards sustainable healthcare. Cataract surgery is the most frequently performed ophthalmic procedure worldwide, with associated waste products contributing to hospitals’ overall environmental footprint. This study intended to evaluate the packaging and manufacturing of various intraocular lenses (IOLs) to identify opportunities for more sustainable practices. 13,894 IOLs from 62 different models implanted at Rothschild Foundation Hospital in 2023 were analyzed in this study. Packaging weight and transport emissions of IOLs were measured via the EcoTransIT calculator. Carbon dioxide emissions from the transport of IOLs ranged from 1.05 to 12.72 kg per 1,000 units, and packaging volumes ranged from 135 to 917 cm³. The disparities in emission rates are due to the variability between different models, underscoring the need to minimize and standardize IOL packaging to reduce the environmental impact. The authors suggest decreasing packaging and using reusable injectors to reduce carbon emissions and stock volume, which may also improve patient access to premium IOLs. 

Cornea

Can a drop of the future go the distance in dry eye disease?

Turns out, water isn’t always the solution, even when it comes to eye drops. A year-long extension of the ESSENCE-2 trial evaluated the safety and efficacy of a novel water-free 0.1% cyclosporine ophthalmic solution (VEVYE) in patients with moderate to severe dry eye disease (DED). The solution uses a formulation that enhances corneal penetration and mitigates common tolerability concerns, including delayed efficacy, the use of preservatives, and installation site reactions. In this open label study, 200 patients applied the treatment twice daily for 52 weeks. Safety assessments tracked ocular and systemic adverse events, while efficacy was measured through corneal staining, tear production, and symptom scores. Over 52 weeks, 80% of patients showed sustained improvements in corneal staining, tear production nearly doubled, and symptoms such as dryness and blurred vision significantly improved. The most common reported adverse events being mild instillation site pain reported in 6.5% of patients. These results build on prior studies by extending the evidence of cyclosporine’s long-term benefit, supporting its role as a well-tolerated, effective option in chronic DED management. The findings are relevant for patients struggling with adherence to older formulations due to delayed onset or discomfort.

Ophthalmology Science

Can AI improve cataract surgery training?

CatSkill, the AI tool not the mountains. The aging population makes cataract surgery training a key feature of ophthalmology residencies. The study team developed an AI-powered video analysis system, called CatSkill, and used the system to develop cataract surgery assessment metrics (CSAMs) for 430 cataract surgeries (of which attendings conducted 254 and residents conducted 176). The CatSkill system involved preprocessing of recorded videos, deep-learning segmentation, detection, and compensation of limbus obstruction, and computation of a number of CSAMs involving (1) the distance between the limbus center and the Purkinje 1 image (anterior surface of the cornea), (2) the distance between the limbus center and the center of the video frame, and (3) the focus level of the limbus region. CatSkill achieved a high Dice coefficient of 94.0% and a high area under the curve of 0.865 in predicting the skill level (attending or resident) of the surgeon. It identified that residents faced more challenges than attendings with stability (eye neutrality, centration, and focus level) during multiple stages of the surgery. This study demonstrates that CatSkill may be a reliable and effective way to assess how residents are progressing through their cataract surgery training.

Collaborative Ocular Melanoma Study (COMS)

Now that you see it, what do you do with it? The COMS was a prospective multicenter trial organized by the National Eye Institute in 1985 to examine mortality outcomes of different treatment options for uveal melanoma. They also examined cancer free survival, metastasis free survival, and years of functional vision. There were three main arms of the study, which differentiated melanomas based upon tumor size. It is important to note that this study does not apply to melanomas of the ciliary body or peripapillary choroid.

Small tumor trial (height <3mm and diameter 5-16mm)

• Objective: do these patients need treatment?
• Methods: observational study with a smaller (N = 188)
• Result: mortality is low for small melanomas, tumor grows slowly
• Takeaway: small choroidal melanomas can be observed safely

Medium tumor trial (height 2.5-10mm and diameter <16mm)

• Objective: do these eyes need enucleation?
• Methods: randomized to enucleation (N = 660) vs. plaque brachytherapy with i125 (N = 657)
• Result: no difference in mortality outcomes at 5 years (enucleation = 81%, plaque = 82%, p = 0.48) so both are options
• Takeaway: plaque brachytherapy is a viable option for medium sized melanomas, long-term data for brachytherapy survival is still pending

Large tumor trial (height > 8mm and/or diameter > 16mm)

• Objective: does radiation improve mortality?
• Methods: randomized to enucleation alone (N = 506) vs. external beam radiation therapy (20 Gy) followed by enucleation (N = 497)
• Result: no difference in mortality outcomes at 5 years (57% enucleation, 62% EBRT then enucleation) or 10 years (40% enucleation, 45% EBRT then enucleation)
• Takeaway: pre-enucleation radiotherapy is no longer used as it is ineffective

The COMS is a landmark study because it helped guide physicians on when and how to treat ocular melanomas, which are the most common primary eye tumors in adults. Although nonmalignant choroidal nevi are more common than choroidal melanomas, all nevi should be evaluated for features concerning for melanoma as choroidal melanomas have high mortality rates.