VanderBeek BL, Yu Y, Cardillo S, Hubbard R. Ophthalmology. 2025 Jan 30:S0161-6420(25)00076-4. doi: 10.1016/j.ophtha.2025.01.022.

Question

How have the rates of diabetic retinal disease and its vision-threatening components, diabetic macular edema and proliferative diabetic retinopathy, changed over the past 20 years?

Background/Summary of Findings

Over the past 20 years, there have been significant improvements made in the delivery of care for patients with diabetes. These developments include new classes of medications, advancements in technology for insulin delivery and glucose monitoring, improved healthcare access with the Affordable Care Act, and promotion of diabetic eye examinations and telemedicine screenings. Counteracting these advancements, however, is an increasing incidence of patients being diagnosed with diabetes who have risk for visual complications from the disease.

Data were abstracted from a database containing healthy claims for members of large commercial and Medicare Advantage health plans. The population is geographically diverse and spans all 50 states. Of the 6 155 025 patients with diabetes during the study period, 1 041 613 received a diagnosis of diabetic retinal disease, an overall prevalence of 16.9%.

Diabetic retinal disease prevalence initially decreased from 13.6% in 2001 to 10.9% in 2007, then increased every year to reach 20.8% in 2021. The prevalence of diabetic macular edema peaked in 2016 but decreased by roughly 10% the subsequent 5 years. Proliferative diabetic retinopathy has been stable among patients with prevalence between 3.2% and 4.0% throughout the 20-year observation period.

Despite an increase in diabetic retinal disease, incident rates of diabetic macular edema and proliferative diabetic retinopathy have improved significantly over the past 20 years.

Clinical Value/Implications

Over the 20-year observation period, although more and more individuals are being diagnosed with diabetes and are, consequently, at risk for vision-threatening diabetic retinal disease, it does not seem to have impacted the incidence of those conditions. Some possible explanations for this phenomenon may be improved medications such as glucagon-like peptide-1 receptor agonists, the rise of anti–vascular endothelial growth factor agents, promotion of diabetic eye examinations, and broadening use of telemedicine. Although the underlying causes for the rise in diabetes still need to be addressed, the silver lining is that current treatments and management strategies have been effective in curbing the rates of diabetic visual complications. It is important to be diligent and persistent about patient education, to make timely diagnoses, and to promptly refer as needed to ensure patients have access to these treatments and programs.

Incidence of Acute Cystoid Macular Edema After Starting a Prostaglandin Analog Compared With Other Classes of Glaucoma Medications

Zhou Y, Bicket AK, Marwah S, Stein JD, Kishor KS; SOURCE Consortium. Ophthalmol Glaucoma. 2025 Jan-Feb;8(1):4-11. doi: 10.1016/j.ogla.2024.07.010.

Question

Do prostaglandin analogs predispose patients with glaucoma to develop acute cystoid macular edema compared with other glaucoma medication classes?

Background/Summary of Findings

Cystoid macular edema has been reported in conjunction with prostaglandin analog treatment in glaucoma patients with history of ocular surgery, lens subluxation, aphakia, as other conditions that may compromise the blood-retina barrier. Some studies have suggested that phakic patients with a normally functioning blood-retina barrier have lower risk for macular edema development secondary to prostaglandin analog treatment.

Participants for this database study were pulled from 10 health systems. A total of 39 948 patients were newly prescribed glaucoma medications. The demographic breakdown of the patient population was 63% White, 24% Black, and 4% Asian American. There were more women (60%) than men (40%) in the study. Patients with preexisting documentation of macular edema secondary to other ocular disease (diabetes, epiretinal membrane, uveitis, vein occlusion), history of uveitis, and intraocular surgery were excluded. Incidence of cystoid macular edema within 3 months of initiating therapy was measured.

Overall, 139 patients (0.35%) developed cystoid macular edema. For users of prostaglandin analogs, beta blockers, alpha agonists, and carbonic anhydrase inhibitors, the incidence of cystoid macular edema was 0.13%, 0.65%, 0.55%, and 1.76%. Users of topical beta blockers, alpha agonists, and carbonic anhydrase inhibitors had higher odds of developing macular edema compared with prostaglandin analogs. Similar to previous studies, pseudophakia itself had higher odds for cystoid macular edema development in the study analysis.

Clinical Value/Implications

The overall risk of cystoid macular edema after initiation of glaucoma medications was quite low. When considering glaucoma treatment, clinicians should reconsider the notion that prostaglandin analogs carry a higher risk for cystoid macular edema compared with other glaucoma medications. Although further studies still need to be conducted, the findings of this database study suggest that clinicians can feel more comfortable prescribing prostaglandin analogs to their glaucoma patients without fear of increased risk for cystoid macular edema development.

Vitreopapillary Findings in Nonarteritic Ischemic Optic Neuropathy Versus Healthy Eyes: A Clinical and OCT Comparison

Hondur AM, Moazami G, Hondur G, Tezel TH. Ophthalmology. 2025 Mar;132(3):327-334. doi: 10.1016/j.ophtha.2024.09.008.

Question

Does the vitreopapillary interface play a role in optic nerve perfusion defects in nonarteritic ischemic optic neuropathy?

Background/Summary of Findings

Crowded optic discs with small cup-to-disk ratio (≤0.20) have been found to be associated with nonarteritic ischemic optic neuropathy. However, crowding of nerve fibers cannot directly lead to ischemia or vascular occlusion, the presumed underlying pathology of this disease. The understanding of various features of nonarteritic ischemic optic neuropathy remains incomplete, including the relationship to a crowded disc and preference for superior involvement with lower altitudinal visual field defect. The potential role of the vitreous in nonarteritic ischemic optic neuropathy was investigated in this study.

The vitreopapillary surface was evaluated using optical coherence tomography scans in 3 groups:

  1. 32 eyes with nonarteritic ischemic optic neuropathy (study group)

  2. 31 healthy individuals with crowded discs (control group 1)

  3. 32 healthy individuals with noncrowded optic discs (control group 2)

The rate of posterior vitreous detachment over the macula was similar between the 3 groups (between 61.3% and 65.6%). However, the posterior hyaloid remained attached to both groups with crowded discs at a significantly higher rate with 81.2% in the nonarteritic ischemic optic neuropathy group and 83.9% in the non–nonarteritic ischemic optic neuropathy group. In contrast, only 43.7% of patients in the healthy noncrowded optic disc group had persistent hyaloid attachment to the disc.

Furthermore, focal vitreopapillary attachments, apart from the vitreous attachments to the disc edges, were noted in more eyes with nonarteritic ischemic optic neuropathy and healthy eyes with crowded discs. Vitreovascular attachments to major vessels over the optic discs were more frequent in eyes with nonarteritic ischemic optic neuropathy (68.8%) compared with healthy eyes with crowded discs (3.2%) and noncrowded discs (6.3%).

After posterior vitreous detachment at the macula, there are increased vitreous forces and traction at the optic nerve because the vitreous is relatively more mobile. The stronger adhesion noted in crowded discs may also explain the predilection for superior involvement of the optic nerve as gravitational forces would be transmitted at a greater extent there compared with the inferior portion of the disc.

Clinical Value/Implications

Crowded discs may have stronger vitreopapillary attachments and a lower rate of complete posterior vitreous detachment. In patients with crowded discs, these persistent attachments with the optic nerve vessels may lead to tractional forces after macular posterior vitreous detachment and potentially contort vessel walls and disrupt blood flow. This mechanism may act as a contributory factor in eyes that already have altered blood flow or vascular insufficiency to the development of nonarteritic ischemic optic neuropathy.

A Multitrait Open-Angle Glaucoma Polygenic Risk Score Stratifies Risk of Glaucoma Diagnosis and Severity in Eyes With Pseudoexfoliation

Kolovos A, Qassim A, Hassall MM, Marshall HN, Schmidt J, Nguyen TT, He W, Mullany S, Hollitt GL, Berry EC, Tang V, Zhou T, Lake S, Mills R, Landers J, Casson RJ, Galanopoulos A, Graham SL, Schulz A, Healey PR, Mitchell P, Goldberg I, Grigg J, Ruddle J, Mackey DA, Burdon KP, Hewitt AW, Seviiri M, Gharahkhani P, Souzeau E, Siggs OM, MacGregor S, Craig JE. Ophthalmology. 2025 Feb 24:S0161-6420(25)00134-4. doi: 10.1016/j.ophtha.2025.02.013. Epub ahead of print. PMID: 40010646.

Question

Can polygenic risk scores built from variants collectively associated with open-angle glaucoma, intraocular pressure, and vertical cup-to-disc ratio stratify individuals with pseudoexfoliation syndrome for their risk of developing pseudoexfoliation glaucoma?

Background/Summary of Findings

Pseudoexfoliation syndrome is a systemic disorder of the extracellular matrix and a strong risk factor for pseudoexfoliation glaucoma. Genetic variants within 15 lead genes are associated with the development of pseudoexfoliation syndrome across multiple populations. LOXL-1 gene is most strongly associated, but variants in LOXL-1 do not stratify glaucoma status in a pseudoexfoliation cohort, nor is the genetic architecture of pseudoexfoliation glaucoma fully understood. Clinically, although pseudoexfoliation glaucoma can evolve from pseudoexfoliation syndrome and demonstrate an aggressive and often blinding disease course, many patients with pseudoexfoliation syndrome never develop glaucoma. Identifying which patients with pseudoexfoliation syndrome are at greatest risk of developing glaucoma and those who are not would greatly impact the ability to individualize management. Previously, a multitrait open-angle glaucoma polygenic risk score was validated and shown to aid in risk stratification. Applying this polygenic risk score within a pseudoexfoliation cohort could prove its value beyond primary open-angle glaucoma and provide a valuable tool to aid in customizing the care of patients with pseudoexfoliation syndrome.

This retrospective cross-sectional multicohort study examined whether 3 polygenic risk scores (glaucoma, intraocular pressure, and vertical cup-to-disc ratio) stratified participants with pseudoexfoliation syndrome by glaucoma status. It secondarily examined whether the glaucoma-polygenic risk score could predict clinically relevant glaucoma outcomes and compared the glaucoma-polygenic risk score distribution of a pseudoexfoliation glaucoma cohort to a primary open-angle glaucoma cohort. Participants of European ancestry with a clinician-reported diagnosis of pseudoexfoliation syndrome and available genotypes were drawn from 3 separate cohort studies. Participants were classified as pseudoexfoliation glaucoma, pseudoexfoliation glaucoma suspects, and pseudoexfoliation without glaucoma. The main outcome measures were the odds of pseudoexfoliation glaucoma and the odds of clinically relevant outcomes.

The results were that participants in the top tertile of the glaucoma-polygenic risk score had greater odds of pseudoexfoliative glaucoma diagnosis (adjusted odds ratio, 4.22; 95% CI, 2.62-6.88; P < .001), greater odds of bilateral central vision loss (adjusted odds ratio, 3.43; 95% CI, 1.49-8.99; P = .007), and greater odds of bilateral incisional surgery (adjusted odds ratio, 3.35; 95% CI, 1.33-10.24; p = .018). Age of pseudoexfoliative glaucoma diagnosis was 1-year younger with each increasing glaucoma-polygenic risk score decile (1.06 years; 95% CI, 0.59-1.53; P < .001). Manifest glaucoma participants with pseudoexfoliation had a comparatively lower glaucoma-polygenic risk score than primary open-angle glaucoma counterparts. Ultimately the authors concluded that polygenic risk scores for open-angle glaucoma, intraocular pressure, and vertical cup-to-disc ratio stratify risk of glaucoma development and disease severity among individuals with pseudoexfoliation syndrome.

Clinical Value/Implications

Pseudoexfoliation can be an extremely aggressive disease with high risk of visual morbidity. This study demonstrated that polygenic risk scores can provide risk stratification for secondary glaucoma in patients with pseudoexfoliation syndrome. Future application of polygenic risk scores in concert with traditional risk factors may help us better surveil patients at risk of poor outcomes and reduce the burden for patients found to be at low risk.

Associations Between School-Based Vision Program Outcomes and School Characteristics in 410 Schools

Kallem M, Guo X, Dai X, Ambrosino C, Nguyen A, Friedman DS, Repka MX, Kourgialis N, Collins M. Ophthalmology. 2025 Apr;132(4):452-460. doi: 10.1016/j.ophtha.2024.11.012.

Question

What are the associations between the outcomes of school-based vision programs and school-level characteristics?

Background/Summary of Findings

Vision health is a critical component of child development and academic success. Vision impairment not adjudicated in childhood is associated with continued vision impairment as an adult and can limit an individual’s employment opportunities, decrease their access to multiple resources that require reading, increase their chances of decreased physical and mental health, and hinder their communication skills. In school, health care services can combat some of the above concerns, but these services are not always available, with communities of lower socioeconomic status most likely to suffer from disparities in access to care.

In a retrospective cross-sectional data analysis between 2016 and 2022 including 410 public schools (mix of elementary, middle, and high schools) in the Northeast with a school-based vision program, Kallem et al assessed rates of vision screening failure, prescriptions for eyeglasses, and community care referrals. Individual student data were aggregated to characterize each school’s particular school-based vision program outcomes and were analyzed with schools’ publicly available socioeconomic and demographic data (student body race and ethnicity composition, proportion of students qualifying for free and reduced-price meals, and proportion of English language learners).

The group analyzed 151 elementary, 155 middle, and 104 high schools with a median proportion of students qualifying for free and reduced-price meals of 87.4% and a plurality of Hispanic students in 61% of those schools. Median rates of vision screening failure, eyeglass prescription, and referral were 38.4%, 25.2%, and 5.4%, respectively. When compared with elementary schools, high schools were associated with a higher rate of screening failures and eyeglass prescriptions and a lower rate of referral. Each 10% increase in the proportion of students qualifying for free or reduced-price meals was associated with a 2.6% increase in screening failure, a 1.8% increase in eyeglass prescription given, and a 0.86% increase in referral rates.

The authors concluded that there is a significant vision care demand in public schools, and that demand is even greater in schools attended by students of lower socioeconomic status. School-based vision programs are important in improving access, and the results of this study showed that there exist opportunities to allocate resources based on individual school needs that may maximize their impact.

Clinical Value/Implications

School-based vision programs are successful and have an impact in the schools and communities they serve. Understanding school-level characteristics, especially socioeconomic status, may provide an opportunity to target where to invest in developing new or expanding current school-based vision programs. Although the current concentration of school-based vision programs is in elementary and middle school, this study highlighted that there should be an increased attention to high school–aged students who are likely currently underserved while still maintaining service to current younger school-aged children.

Association Between Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Study

Chou CC, Pan SY, Sheen YJ, Lin JF, Lin CH, Lin HJ, Wang IJ, Weng CH. Ophthalmology. 2025 Apr;132(4):381-388. doi: 10.1016/j.ophtha.2024.10.030.

Question

Does semaglutide increase the risk of nonarteritic anterior ischemic optic neuropathy in the general population?

Background/Summary of Findings

Several medications have, in the past, been shown to increase the risk of nonarteritic anterior ischemic optic neuropathy, and recently, a single-center cohort study suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may need to be added to that list, as they found in a retrospective single-center study that glucagon-like peptide-1 receptor agonists were associated with a higher risk of nonarteritic anterior ischemic optic neuropathy. Glucagon-like peptide-1 receptor agonists have been shown to be effective in the treatment of diabetes and obesity as well as in protecting cardiovascular health, and as a result, this class of medications is being prescribed much more frequently and public awareness of these agents is significant. Therefore, it is important to know whether the previously reported association between glucagon-like peptide-1 receptor agonists and nonarteritic anterior ischemic optic neuropathy extends beyond the single center that initially highlighted the relationship between the two.

Chou et al, employing a retrospective cohort study design, used a deidentified global electronic medical records database including patient data from 160 health care organizations across 21 countries to study the relationship between semaglutide and nonarteritic anterior ischemic optic neuropathy. The data comprised individuals with type 2 diabetes mellitus or obesity, and individuals were further placed into several subgroups: type 2 diabetes mellitus only, obesity only, and type 2 diabetes mellitus with obesity. The effects of semaglutide were compared against those of glucose-lowering or weight-loss medications other than glucagon-like peptide receptor agonists, and outcomes, defined as the occurrence of nonarteritic anterior ischemic optic neuropathy, were evaluated at 1, 2, and 3 years of follow-up.

The final analysis included 37 314 participants with type 2 diabetes mellitus only, 129 690 participants with obesity only, and 130 216 participants with both type 2 diabetes mellitus and obesity. The results indicated that the administration of semaglutide was not associated with the development of nonarteritic anterior ischemic optic neuropathy in the type 2 diabetes mellitus-only group (1-year follow-up: HR, 2.32; 95% CI, 0.60-8.97; 2 years: HR, 2.31; 95% CI, 0.86-6.17; 3 years: HR, 1.51; 95% CI, 0.71-3.25), the obesity-only group (1-year follow-up: HR, 0.41; 95% CI, 0.08-2.09; 2 years: HR, 0.67; 95% CI, 0.20-2.24; 3 years: HR, 0.72; 95% CI, 0.24-2.16), and the type 2 diabetes mellitus with obesity group (1-year follow-up: HR, 0.81; 95% CI, 0.42-1.57; 2 years: HR, 1.2; 95% CI, 0.74-1.94; 3 years: HR, 1.19; 95% CI, 0.78-1.82).

The authors concluded that the findings suggest that semaglutide may not be associated with an increased risk of nonarteritic anterior ischemic optic neuropathy in the general population and that avoidance of semaglutide based on the potential risk of nonarteritic anterior ischemic optic neuropathy is likely not warranted.

Clinical Value/Implications

Withholding semaglutide from a patient who could benefit from improved blood sugar control, weight loss, and cardio-protection because of a previous single-center study is likely an inappropriate risk calculation according to these study results. As more patients are eligible for glucagon-like peptide-1 receptor agonists, they should be apprised of the available research and be allowed to make an informed decision on their care until more conclusive evidence is gathered.