Loss to Follow-Up in Patients With Proliferative Diabetic Retinopathy Treated With Anti–Vascular Endothelial Growth Factor Therapy and/or Panretinal Photocoagulation in the United States

Khurana RN, Wang JC, Zhang S, Li C, Lum F. Ophthalmol Retina. 2024;8(10):953-961. doi:10.1016/j.oret.2024.04.016

Question

In patients with a history of proliferative diabetic retinopathy treated with panretinal photocoagulation and/or anti–vascular endothelial growth factor therapy, what is the rate of being lost to follow-up? Which groups should be targeted as far as optimizing adherence and compliance to treatment and follow-up?

Background/Summary of Findings

The American Academy of Ophthalmology Intelligent Research in Sight Registry data were used for this retrospective cohort study, which included 73 595 eyes of 56 590 patients with proliferative diabetic retinopathy. Loss to follow-up was defined as no follow-up within 12 months from the last treatment. The rate of loss to follow-up was found to be between 10% and 12% among patients with proliferative diabetic retinopathy treated with anti–vascular endothelial growth factor injections and/or panretinal photocoagulation. Risk factors included Black or African American race and ethnicity, Hispanic ethnicity, baseline vision worse than 20/40, private insurance, residing in the Southern United States, and unilateral disease. Compared with patients not lost to follow-up, patients who were lost to follow-up had a higher percentage of visual acuity worse than 20/200 and a lower percentage of patients with vision better than 20/400. Similarly, patients who were not lost to follow-up had lower rates of iris neovascularization, vitreous hemorrhage, and tractional retinal detachment compared with patients who were lost to follow-up. There was no significant difference between loss to follow-up rates for individuals treated with panretinal photocoagulation and anti–vascular endothelial growth factor injections, a somewhat surprising finding given panretinal photocoagulation is usually considered for patients with compliance concerns given fewer treatments are needed vs anti–vascular endothelial growth factor injections. Better adherence was associated with impending bilateral vision loss with bilateral proliferative diabetic retinopathy or new proliferative diabetic retinopathy complications, good vision at baseline, and visual improvement.

Clinical Value/Implications

Adherence to treatment and the recommended follow-up schedule is of paramount importance to preserving sight, particularly in patients who are at high risk for permanent vision loss due to proliferative diabetic retinopathy. Good vision in these patients can be seen as a double-edged sword: although these patients had good results from proliferative diabetic retinopathy treatment, having good vision may have given them a false sense of security and they were more likely to be lost to follow-up in this study. This underscores the importance of potentially emphasizing and providing additional education regarding the importance of follow-up to these individuals to maintain their current vision and prevent worsening of their condition. Patients who had a poor visual outcome were also found to be at higher risk for being lost to follow-up. These individuals may have decreased adherence to the follow-up schedule because they believed the treatment did not help their vision and were less motivated to return for further care. Patients with private insurance and higher out-of-pocket expenses may also be more likely to be lost to follow-up. Individuals from the Southern United States have been found to have higher rates of severe vision loss that were associated with poverty. In this study, individuals from the Southern United States were similarly more likely to be lost to follow-up than those in the Midwest and Western regions. Furthermore, ethnicity is known to influence adherence in medical care due to language barriers, cultural beliefs, socioeconomic status, and trust in the health care system. Social determinants of health affect adherence in management of diabetic retinopathy. Clinicians should be aware of these risk factors and design ways to coordinate care and target those at higher risk for being lost to follow-up after treatment for proliferative diabetic retinopathy.

Long-Term Systemic Use of Calcium Channel Blockers and Incidence of Primary Open-Angle Glaucoma

Tavakoli K, Sidhu S, Radha Saseendrakumar B, Weinreb RN, Baxter SL. Ophthalmol Glaucoma. 2024;7(5):491-498. doi:10.1016/j.ogla.2024.06.003

Question

Is there an association between calcium channel blocker use and primary open-angle glaucoma?

Background/Summary of Findings

The National Institutes of Health All of Us dataset, considered to be a demographically, geographically, and medically diverse cohort, was used for the analyses. The database consisted of 213 424 individuals aged 40 years and older and included historically underrepresented populations with 31.1% identifying themselves as Black or African American and 15.3% as Hispanic. Individuals with a diagnosis of glaucoma prior to starting any class of blood pressure medication were excluded. Within the cohort, 2772 participants (1.3%) developed glaucoma with a mean age of 73 years. Participants who developed glaucoma were more likely to be Black or African American compared with those who did not develop primary open-angle glaucoma. Use of dihydropyridine calcium channel blockers was associated with a significantly higher risk of developing glaucoma after adjusting for demographic factors, medical conditions, and other blood pressure medications.

Clinical Value/Implications

When managing patients, in particular glaucoma suspects, it is important to have a medication list for each patient to properly assess potential risk factors for glaucoma development. Given that hypertension and glaucoma both affect the aging population, at times simultaneously, further research is needed to find a balance between treating hypertension without significantly and negatively affecting glaucoma outcomes.

Rapid Retinal Nerve Fiber Layer Thinning in the Unaffected Contralateral Eyes of Patients With Unilateral Normal-Tension Glaucoma: A Retrospective Observational Study

Song JE, Lee EJ, Kim TW. Ophthalmol Glaucoma. 2024;7(5):431-439. doi:10.1016/j.ogla.2024.04.009

Question

In patients with unilateral normal tension glaucoma, how does the contralateral unaffected eye’s rate of retinal nerve fiber layer thinning compare with that of healthy subjects over time?

Background/Summary of Findings

A total of 95 patients with unilateral normal tension glaucoma and 61 healthy controls were followed over a minimum of 4 years. Each patient had at least 5 reliable retinal nerve fiber layer thickness measurements with optical coherence tomography. Control subjects had bilateral healthy eyes with intraocular pressure less than 21 mm Hg, normal visual field, and normal healthy optic nerve appearance as determined by 2 glaucoma specialists. The unaffected eyes of patients with unilateral normal tension glaucoma experienced significantly faster retinal nerve fiber layer thinning compared with the healthy eyes, specifically in the inferior/temporal sector. The rate of retinal nerve fiber layer thinning in the unaffected eyes of patients with normal tension glaucoma was significantly associated with higher baseline retinal nerve fiber layer thickness and worse baseline visual field mean deviation. The rate of retinal nerve fiber layer thinning in the unaffected eyes in cases of unilateral normal tension glaucoma was comparable to that of affected and treated contralateral eyes with normal tension glaucoma. Overall, only 20% of the unaffected eyes showed glaucoma conversion in the present study over 4 years of follow-up. It is possible that over a longer period of observation, the rate of conversion to glaucoma would be higher. Study findings may indicate that progressive structural damage is already occurring in the unaffected fellow eyes despite the absence of glaucomatous damage.

Clinical Value/Implications

During long-term follow-up, the contralateral normal eyes of patients with unilateral glaucoma eventually progress to bilateral glaucoma in many cases. Consistent with the typical sequence of neuroretinal rim loss, the inferior/temporal rim in this study was the area of most rapid retinal nerve fiber layer thinning in the unaffected eyes of patients with unilateral normal tension glaucoma. This area of the optic nerve needs more careful monitoring for early glaucomatous changes. The findings in this study suggest that in patients with unilateral normal tension glaucoma, prophylactic treatment of the contralateral/unaffected eye could be considered when there is a risk for developing glaucoma.

Agrón E, Domalpally A, Chen Q, et al. Ophthalmology. 2024;131(10):1164-1174. doi:10.1016/j.ophtha.2024.04.011

Question

What is the 5-year rate of progression to late age-related macular degeneration using an updated simplified severity scale (levels 0 to 4) when the risk of progression is updated to factor in the presence or absence of reticular pseudodrusen and when noncentral geographic atrophy is included as an outcome, rather than a risk factor?

Background/Summary of Findings

Longitudinal data from the Age-Related Eye Disease Study have been previously used to develop the Age-Related Eye Disease Study 9-step severity scale, the advanced age-related macular degeneration risk calculator and the Age-Related Eye Disease Study simplified severity scale. These risk calculators have different utilities, with the simplified severity scale being the most applicable to clinical practice. All of the previous calculators are based on the traditional macular features of soft drusen and pigmentary abnormalities and consider noncentral geographic atrophy as a risk factor, not an end point on its own. Modern technology has, however, elucidated the presence of reticular pseudodrusen (also known as subretinal drusenoid deposits) as a new feature that increases the risk of progression in excess of the traditional macular findings. Accordingly, any risk calculator neglecting to include reticular pseudodrusen is likely suboptimal. Additionally, the presence of any form of geographic atrophy is currently considered to be indicative of late age-related macular degeneration, not just central atrophy. The purpose of this study was to modernize the Age-Related Eye Disease Study simplified severity scale to include reticular pseudodrusen in the risk calculation and noncentral geographic atrophy as an outcome, to report the 5-year risks of progression to late age-related macular degeneration at the person level, and to perform external validation of the updated scale using the Age-Related Eye Disease Study 2 dataset. As color fundus photography was the only available imaging technology in the original study, to detect the presence of reticular pseudodrusen using the Age-Related Eye Disease Study dataset, a deep learning algorithm was implemented and automated the grading of reticular pseudodrusen on the color fundus photographs.

Compared with the original simplified severity scale, the inclusion of noncentral geographic atrophy increased the rate of severity at all levels. The additional inclusion of reticular pseudodrusen as a risk factor resulted in a substantially increased risk of progression across all levels when compared with patients without reticular pseudodrusen. Specifically, the 5-year progression rates for levels 0 to 4 were 0.3%, 4.3%, 11.6%, 26.7%, and 50.0%, respectively, for participants without reticular pseudodrusen at baseline and 2.8%, 8.0%, 29.0%, 58.7%, and 72.2%, respectively, for participants with reticular pseudodrusen at baseline. In external validation on the Age-Related Eye Disease Study 2, for levels 2 to 4, the progression rates were similar: 15.0%, 27.7%, and 45.7% (reticular pseudodrusen absent) and 26.2%, 46.0%, and 73.0% (reticular pseudodrusen present), respectively.

Clinical Value/Implications

The updated Age-Related Eye Disease Study severity scale remains simple to use, more closely reflects modern clinical practice and definitions of geographic atrophy, and highlights how critical it is that we recognize reticular pseudodrusen/subretinal drusenoid deposits in our patients with suspected age-related macular degeneration, as their presence greatly increases the risk of developing late age-related macular degeneration and vision loss.

Repeated Low-Level Red Light Therapy for Myopia Control in High Myopia Children and Adolescents: A Randomized Clinical Trial

Xu Y, Cui L, Kong M, et al. Ophthalmology. 2024;131(11):1314-1323. doi:10.1016/j.ophtha.2024.05.023

Question

What is the safety and effectiveness of repeated low-level red light, which is a newly available treatment for myopia control in children and adolescents with high myopia?

Background/Summary of Findings

Despite the growing prevalence and potential vision-threatening complications of myopia, there remains a gap in evidence-based strategies for its effective control and management. Repeated low-level red light therapy has emerged as a potential strategy for myopia control. Currently, a portable desktop device allows repeated low-level red light treatment to be done at home, making this a convenient treatment option.

Using a multicenter, randomized, parallel-group, single-blind clinical trial design, 192 children aged 6 to 16 years were enrolled. Each child had at least 1 eye with myopia of cycloplegic spherical equivalent refraction at least -4.0 D, astigmatism of ≤ 2.0 D, anisometropia of ≤ 3.0 D, and best-corrected visual acuity of 0.2 logarithm of the minimum angle of resolution or better. Follow-up was completed by April 2023. Patients were assigned randomly at a 1:1 ratio to intervention (repeated low-level red light treatment plus single-vision spectacles) or control (single-vision spectacles) groups. The repeated low-level red light treatment was administered for 3 minutes per session, twice daily with a minimum interval between sessions of 4 hours, 7 days per week until the 12-month follow-up. The primary and key secondary outcomes were changes in axial length and cycloplegic spherical equivalent measured at baseline and the 12-month follow-up visit. Participants who had at least 1 postrandomization follow-up visit were analyzed for treatment efficacy.

After 12 months, the adjusted mean change in axial length was -0.06 mm (95% CI, -0.10 to -0.02 mm) and +0.34 mm (95% CI, 0.30-0.39 mm) in the intervention and control groups, respectively. A total of 48 participants (53.3%) in the intervention group were still experiencing axial shortening greater than 0.05 mm at the 12-month follow-up. The mean spherical equivalent change after 12 months was 0.11 D (95% CI, 0.02-0.19 D) and -0.75 D (95% CI, e0.88-e0.62 D) in the intervention and control groups, respectively. No serious adverse effects developed during the trial.

Clinical Value/Implications

The authors concluded that repeated low-level red light therapy demonstrated stronger treatment efficacy among those with high myopia, with 53.3% experiencing substantial axial shortening. Repeated red light therapy appears to be an additional viable treatment method to help reduce myopia progression. Further study is needed to understand whether the 12-month treatment effect persists or regresses after discontinuing therapy and to additionally clarify what the position is of repeated low-level red light within the myopia control landscape.

Nationwide Prevalence and Geographic Variation of Idiopathic Intracranial Hypertension Among Women in the United States

Fraz MA, Kim BM, Chen JJ, et al. Ophthalmology. Published online November 5, 2024. doi:10.1016/j.ophtha.2024.10.031

Question

What is the nationwide prevalence and geographic distribution of idiopathic intracranial hypertension among women in the United States?

Background/Summary of Findings

Obesity is the primary risk factor for idiopathic intracranial hypertension. With obesity on the rise, idiopathic intracranial hypertension may also be on the rise. Past epidemiological studies on idiopathic intracranial hypertension have been limited to individual health systems, counties, or states and as a result lack generalizability. Examining whether there is geographic variation by assessing the entire United States may help to clarify the overall burden of idiopathic intracranial hypertension, examine disparities in health care access, and as a result inform future research on multiple facets of this condition.

The authors combined Medicaid, electronic health record registry, and US Census Bureau data to estimate the nationwide and state-specific prevalence of idiopathic intracranial hypertension among women in the United States. Included were female Medicaid beneficiaries aged 18 to 55 years with idiopathic intracranial hypertension diagnoses and prescriptions for acetazolamide or methazolamide in 2018. The total number of patients with idiopathic intracranial hypertension in the United States and respective states was calculated by dividing the total Medicaid beneficiaries with idiopathic intracranial hypertension by the proportion of patients with idiopathic intracranial hypertension insured by Medicaid. Census data were then used to calculate prevalence. The main outcome measure was to compare the geographic distribution of idiopathic intracranial hypertension to obesity prevalence data. This outcome measure was externally validated.

A total of 13 959 female Medicaid beneficiaries with idiopathic intracranial hypertension in 2018 were identified, of whom 6828 had a qualifying prescription for acetazolamide or methazolamide. In  the Intelligent Research in Sight Registry and Sight Outcomes and Research Collaborative, the pooled proportion of patients with idiopathic intracranial hypertension with Medicaid insurance was 25% (95% CI: 16%-33%) (figure 2), suggesting that there were 27 312 women aged 18 to 55 years with idiopathic intracranial hypertension taking acetazolamide or methazolamide in the United States in 2018 (6828/0.25 = 27 312). Dividing this by the total female population aged 18 to 55 years yielded an estimated prevalence of 3.44 per 10 000. There was significant geographic variation in idiopathic intracranial hypertension with higher prevalence in states where obesity was also more common and the top 2 states (Kentucky and Louisiana) having a prevalence 3 times greater than nationwide averages.

Clinical Value/Implications

The authors state that prevalence data are a better indicator of disease burden and can be useful for determining how resources should be allocated to combat disease. Although the geographic pattern of idiopathic intracranial hypertension in this study generally mirrored the state-level pattern of obesity, this finding was not universal and might speak to additional unique factors such as access to care and availability of certain specialty care providers. Understanding that there are state and regional variations may provide future opportunities to target efforts aimed at preventing idiopathic intracranial hypertension and its burden when detected.