Crump C, Sundquist J, Sieh W, Sundquist K. Risk of Alzheimer’s Disease and Related Dementias in Persons with Glaucoma: A National Cohort Study. Ophthalmology. 2024;131(3):302-309. doi:10.1016/j.ophtha.2023.10.014

Question

Is there an association between glaucoma and dementia?

Background/Summary of Findings

A link between glaucoma and dementia has previously been speculated, although attempts to study a link have provided conflicting results. This study used available nationwide data for 3.5 million people in Sweden (the Swedish Hospital and Outpatient Registers) to assess a possible link. Medical record analysis of people in this registry who were diagnosed with glaucoma (with no preceding diagnosis of dementia) from 1995 to 2017 was undertaken. Each patient with glaucoma was matched against 10 controls from the nonglaucoma general population of the same birth month and year. Rates of the diagnoses of Alzheimer disease, vascular dementia, and all-cause dementia were compared among the groups.

Clinical Value/Implications

Analysis of the data showed higher rates of dementia in the glaucoma group. Patients with glaucoma had 35% greater risk of Alzheimer disease, 65% higher risk of vascular dementia, and 55% higher risk of all-cause dementia compared with controls. Increasing age of glaucoma diagnosis was associated with increased risk of dementia, and different forms of glaucoma carried different risk of type of dementia. This information can be used in counseling patients with glaucoma and their primary care physicians.

Association of Sociodemographic Characteristics with Pediatric Vision Screening and Eye Care: An Analysis of the 2021 National Survey of Children’s Health

Antonio-Aguirre B, Block SS, Asare AO, et al. Association of Sociodemographic Characteristics with Pediatric Vision Screening and Eye Care: An Analysis of the 2021 National Survey of Children’s Health. Ophthalmology. 2024;131(5):611-621. doi:10.1016/j.ophtha.2023.12.005

Question

What are the associations between sociodemographic and health characteristics and the receipt of eye care among children aged 17 years and younger in the United States?

Background/Summary of Findings

Vision screening and routine eye examinations can help identify and subsequently treat ocular conditions with the potential to result in irreversible vision impairment. It is especially important to detect refractive errors in the school-age population given the association between uncorrected refractive error and its negative impact on academic performance. Presently, 33 states mandate vision screening for preschool-age children, and 41 states require screenings in the school-age population. Notably, children who are uninsured, as well as racial and ethnic minority populations, are more likely to have unmet vision needs and face barriers to accessing timely care.

Using a cross-sectional study design, data from the National Survey of Children’s Health (NSCH) were used to investigate the associations between sociodemographic and health characteristics and the receipt of eyecare among children in the United States aged 17 years and younger. The NSCH is a nationally representative and population-based survey of randomly sampled households. The main outcome measures were caregiver-reported vision screenings, referral to an eye doctor after vision screening, eye doctor visits, and prescription of corrective lenses. To measure these outcomes, weighted prevalence calculations were applied and logistic regression was performed to explore associations between reported eyecare and demographic, health, and parent-related variables.

Caregivers reported that 53.2% of children had a vision screening at least once (if younger than 5 years of age) or within the past 2 years (if older than 5 years of age). Of those screened, 26.9% were referred to an eye doctor. Overall, 38.6% of all children had a previous eye doctor visit, and among them, 55.4% were prescribed corrective lenses during the visit. Factors associated with decreased odds of vision screening included younger age, lack of health care visits, no insurance coverage, parent education high school or less, and lower household income. Non-White ethnicities, households with a non-English primary language, and lower incomes were more likely to be referred to an eye doctor after vision screening. Lower rates of eye doctor visits were associated with younger age, lack of insurance coverage, and primary household languages other than English.

Clinical Value/Implications

This study highlights that there remains a substantial gap in screening and treating children for common vision disorders. This gap is especially prevalent in children from disadvantaged backgrounds. Continued efforts need to be put forth to raise overall awareness of the criticality of vision and eye health in pediatric development, with a particular concentration on underserved populations.

Khanani AM, Kotecha A, Chang A, et al. TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2. Ophthalmology. Published online February 19, 2024. doi:10.1016/j.ophtha.2024.02.014

Question

What is the 2-year efficacy, durability, and safety of the bispecific antibody faricimab in treatment-naive patients with neovascular age-related macular degeneration aged 50 years and older?

Background/Summary of Findings

Intravitreal anti−vascular endothelial growth factor therapy has significantly reduced the likelihood of severe vision loss in patients with neovascular age-related macular degeneration. Real-world outcomes are, however, not always as successful as those found in well-controlled prospective clinical trials. The treatment burden associated with the frequent injections is one of the likely contributors to these worsened real-world outcomes, owing to undertreatment. More durable treatments, requiring less frequent injections and subsequent reduced patient burden, have the potential to further improve neovascular age-related macular degeneration care.

Faricimab is a bispecific antibody that independently binds and neutralizes angiopoietin-2 and vascular endothelial growth factor A, and it has been proposed that this simultaneous inhibition may, through vascular stabilization, result in more durable efficacy than standalone vascular endothelial growth factor inhibition.

TENAYA (NCT03823287) and LUCERNE (NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials across sites worldwide. Patients with neovascular age-related macular degeneration who were aged 50 years and older and naive to treatment were randomized 1:1 to either intravitreal faricimab 6.0 mg up to every 16 weeks (after 4 initial doses given every 4 weeks) or aflibercept 2.0 mg every 8 weeks (after 3 initial doses given every 4 weeks). Faricimab patients had fixed dosing of every 16, 12, or 8 weeks based on protocol-defined disease activity at weeks 20 and 24 up to week 60 and were then followed up to week 108 by a treat and extend–based personalized treatment interval regimen.

A total of 83.9% of patients meeting eligibility criteria and enrolled completed the study (n = 555 faricimab and n = 558 aflibercept). Best-corrected visual acuity change from baseline at 2 years was comparable between faricimab and aflibercept in TENAYA (+3.7 letters [+2.1 to +5.4] and +3.3 letters [+1.7 to +4.9], respectively) and in LUCERNE (+5.0 letters [+3.4 to +6.6] and +5.2 [+3.6 to +6.8], respectively). At week 112 in TENAYA and LUCERNE, respectively, 59.0% and 66.9% achieved every-16-weeks faricimab dosing, increasing from year 1, and 74.1% and 81.2% achieved greater than or equal to every-12-weeks dosing. In both trials, the majority of ocular adverse events were mild or moderate in severity and consistent with what would be expected within a neovascular age-related macular degeneration population treated with intravitreal injections. The proportion of patients with serious ocular adverse events in the study eye through week 112 were low and comparable between TENAYA (faricimab [4.2%]; aflibercept [3.9%]) and LUCERNE (faricimab [4.5%]; aflibercept [4.9%]).

Clinical Value/Implications

Both LUCERNE and TENAYA showed that the vast majority of patients achieved comparable structural and functional results with faricimab 6.0 mg when compared with aflibercept 2.0 mg with less frequent dosing. The treatment intervals successfully applied in this study may reflect a more tolerable treatment burden for our patients and have the potential to improve real-world outcomes.

The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08% (Polihexanide) and Placebo versus PHMB 0.02% and Propamidine 0.1%

Dart JKG, Papa V, Rama P, et al. The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08% (Polihexanide) and Placebo versus PHMB 0.02% and Propamidine 0.1. Ophthalmology. 2024;131(3):277-287. doi:10.1016/j.ophtha.2023.09.031

Question

Is polyhexanide 0.08% as effective as traditional dual therapy of polyhexanide 0.02% and propamidine 0.1% in the treatment of Acanthamoeba keratitis?

Background/Summary of Findings

Acanthamoeba keratitis is a severe form of microbial keratitis that disproportionately leads to surgical outcomes compared with other types of microbial keratitis. Although polyhexanide 0.02% to 0.04% and chlorhexidine 0.02% to 0.04% are often compounded for topical use in the management of Acanthamoeba keratitis and propamidine isethionate 0.1% (Brolene)—a general topical disinfectant—is available over the counter in certain parts of the world, there are no commercially available topical eye drops that are approved for the treatment of Acanthamoeba keratitis in the United States or Europe. The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial—an orphan drug review—compares the efficacy of polyhexanide 0.08% plus placebo with conventional therapy of polyhexanide 0.02% and propamidine 0.1% in the medical management of Acanthamoeba keratitis. Patients were grouped by disease staging (stage I-III) and were then randomized to receive one of the 2 therapies described above. They were double blinded and observed over a year. The primary endpoint was medical cure rate by 12 months.

Clinical Value/Implications

Although the authors initially speculated that polyhexanide 0.08% would provide superior results to the comparator, this was not borne out, and the 2 regimens were found to be approximately equivalent in medical cure rate. Secondary outcomes of mean and median visual outcomes, treatment failures, and quality-of-life scores were also similar among the 2 strategies. Polyhexanide 0.08% appears to be noninferior to conventional comparator dual therapy. Although this study was performed in Europe, as its focus is on an orphan drug, it set the stage for further study and eventual commercial availability in the United States. That said, conventional dual therapy of compounded polyhexanide 0.02% plus Brolene remains as effective.

An additional interesting finding was the comparison of culture positivity versus polymerase chain reaction positivity (all eyes were confocal positive). Although polymerase chain reaction outperformed culture (52% to 29%), neither was particularly sensitive when compared with confocal (a positive confocal was an inclusion criterion for the study). As polymerase chain reaction is gaining attention in the management of microbial keratitis, its strengths and limitations compared with conventional strategies are worth paying attention to.

Prevalence and Cause of Loss of Visual Acuity and Visual Field in Highly Myopic Eyes: The Beijing Eye Study

Jonas JB, Jonas RA, Xu J, Wang YX. Prevalence and Cause of Loss of Visual Acuity and Visual Field in Highly Myopic Eyes: The Beijing Eye Study. Ophthalmology. 2024;131(1):58-65. doi:10.1016/j.ophtha.2023.08.026

Question

What is the prevalence of and what are the causes of loss of visual acuity and visual field in highly myopic eyes?

Background/Summary of Findings

Past studies have shown that myopic macular degeneration is one of the most common causes of irreversible vision impairment and blindness worldwide and that the risk of visual acuity loss nonlinearly increases with longer axial length. However, most of these studies did not assess its specific prevalence in myopic or highly myopic groups, examine the presence and extent of visual defects in these specific groups, or consider a concomitant high myopia–associated optic neuropathy.

In this population-based study, 4439 participants underwent ophthalmological and systemic examinations including frequency doubling perimetry with a determination of the prevalence of vision impairment causes being the main outcome. High myopia was defined as a refractive error of 6 diopters (D) or axial length greater than 26.0 mm. Two hundred twelve eyes from 154 participants met the criteria for high myopia and had a mean refractive error of -9.87 ± 3.70 D and a mean axial length of 27.2 ± 1.3 mm. Moderate to severe vision impairment was found in 40 eyes. The primary causes of moderate and severe vision impairment and blindness were myopic macular degeneration in 58%, age-related macular degeneration in 2%, and branch macular vein occlusion in 2%. The secondary causes were myopic macular degeneration in 8% and optic atrophy in 28% (further differentiated into nonglaucomatous [18%] and glaucomatous [10%]). Myopic macular degeneration prevalence increased significantly with each subsequent diopter greater than -6.00. The prevalence of myopic macular degeneration was 1.6% in the -6 to -7 D group and increased to 64% in the less than -15 D group. Progressively higher refractive error increased the likelihood of concomitant optic neuropathy and that optic neuropathy causing vision impairment.

Clinical Value/Implications

Optic neuropathy of both glaucomatous and nonglaucomatous types contributes to loss of visual acuity and visual field in highly myopic eyes. Understanding the prevalence of these conditions should help raise physician awareness when examining patients with refractive errors more susceptible to myopic-associated optic neuropathies.