Most-talked-about journal articles bring ‘awareness’ to AMD


Two of the top 10 “most-talked-about” articles in JAMA Ophthalmology are about age-related macular degeneration (AMD). One of the current top 5 “most-read” articles in the American Journal of Ophthalmology is also about AMD. Here are a brief synopsis of those three papers.

By Michelle Dalton, ELS

Two of the top 10 “most-talked-about” articles in JAMA Ophthalmology are about age-related macular degeneration (AMD). One of the current top 5 “most-read” articles in the American Journal of Ophthalmology is also about AMD.

Here, a brief synopsis of those three papers:

From JAMA Ophthalmology

The first of the two papers, “Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care,” by David C. Neely, MD, et al.,1used a large sample of older adults, judged to have normal macular health in both eyes by their ophthalmologist or optometrist based on a dilated eye examination to determine how many eyes had gone undiagnosed.

The authors found 320 of 1,288 eyes had AMD, despite no diagnosis of AMD in the primary eye care medical record, including 30% with undiagnosed large drusen, long considered a hallmark of the disease.

In this cross-sectional study, participants consisted of 644 adults 60 years or older enrolled in the Alabama Study on Early Age-Related Macular Degeneration (ALSTAR) from May 1, 2009, through Dec. 31, 2011, and seen by 31 primary eye care ophthalmologists or optometrists.

The sample consisted of 1,288 eyes from 644 participants: 231 male (35.9%), 413 (64.1%) female; mean age, 69.4 ± 6.1 years. The overwhelming majority (n = 611, 94.9%) were Caucasian. The majority of participants were in their 60s (59%), followed by people in their 70s (35.1%). However, 38 participants (5.9%) were in their 80s.



 Those likely undiagnosed

Older people, men, those with worse visual acuity, and those with less than a high school education were likely to be undiagnosed for AMD, as were those who were pseudophakic or who had hypertension. Those with better mental status were also likely to have undiagnosed AMD.

However, smoking status, family history of AMD, and other medical comorbidities had little effect on whether or not an eye was diagnosed.

“We found that 25% of eyes with no diagnosis of AMD in the medical record or notations about AMD characteristics in the fundus examination actually had AMD according to a clinical classification staging system,” the authors wrote.

About 30% of the undiagnosed eyes had large drusen, an indicator that those patients could have been candidates for nutritional supplements (the Age-Related Eye Disease Study [AREDS] formulation), but only 3 of the 99 eyes (3%) with intermediate AMD were on an AREDS nutritional supplementation regimen.

The authors noted both ophthalmologists and optometrists “could benefit from better training in identifying AMD in the dilated fundus exam.”

Finally, “as treatments for the earliest stages of AMD are developed in the coming years, correct identification of AMD in primary eye care will be critical for routing patients to treatment as soon as possible so that the disease can be treated in its earliest phases and central vision loss avoided.”



Second JAMA Ophthalmology paper

In the second JAMA Ophthalmology paper, “Generational Differences in the 5-year Incidence of Age-Related Macular Degeneration,” Karen J. Cruickshanks, PhD, et al.2 found that aging “Baby Boomers” may have better retinal health in their older age than generations before them did.

The authors evaluated data from the longitudinal cohort Beaver Dam Eye Study (March 1, 1988, through Sept. 15, 1990, and March 1, 1993, through June 15, 1995) and a companion study, the Beaver Dam Offspring Study (June 8, 2005, through Aug. 4, 2008, and July 12, 2010, through March 21, 2013)

Among the 4,819 participants, the mean baseline age of the cohort was 54 ± 11 years. Fewer than half the participants were male (2,117, 43.9%). The 5-year age- and sex-adjusted incidence of AMD was 8.8% in the Greatest Generation (born between 1901-1924), 3.0% in the Silent Generation (born between 1925-1945), 1.0% in the Baby Boomer Generation (born between 1946-1964), and 0.3% in Generation X (born between 1965-1984).

The authors did not have an explanation for the decline, but noted the pattern was consistent with reported declines in risks for cardiovascular disease and dementia.



From the AJO

In “Estimating Public and Patient Savings from Basic Research-A Study of Optical Coherence Tomography (OCT) in Managing Anti-angiogenic Therapy,” Matthew A. Windsor, MD, et al.3 found the use of OCT yielded substantial savings by government agencies. In fact, from 2008 to 2015, the U.S. Government and neovascular AMD patients have accrued an estimated savings of $9 billion and $2.2 billion, respectively, from the use of OCT to guide personalized anti-vascular endothelial growth factor (anti-VEGF) treatment.

The authors sought to compare patient and Medicare savings from the use of OCT in guiding therapy for neovascular AMD to the research investments made in developing OCT by the National Institutes of Health (NIH) and the National Science Foundation (NSF). As the arrival of the anti-VEGF biologics replaced other treatments, ophthalmologists and other eye care professionals began adopting OCT technologies to efficiently use the effective (but expensive) intravitreal injections.

Within the treating ophthalmic community, there remains some controversy over which treatment regimens are most effective for AMD - PRN, monthly, or treat-and-extend. The authors noted “most studies have shown noninferiority for these maintenance protocols,” and hypothesized that implementing OCT technologies has been a key factor.

“Without the high-resolution, noninvasive macular imaging by OCT, these personalized regimens would be significantly more difficult to accomplish because physicians would have to treat according to the fixed-dosing regimen used in the pivotal trials, or possibly rely on more invasive and expensive angiography to direct therapy,” the authors wrote.



Cost-saving analysis

In their study, they compared cost savings between patients on Medicare who had OCT-enabled, personalized-treatment protocols and those on a fixed- treatment schedule.

The group performed a meta-analysis of the literature to determine the number of injections per year an average AMD patient would receive on the PRN or treat-and-extend treatment protocols during the maintenance phase of his or her therapy.

(For the purposes of their analysis, the group defined “maintenance phase” as the period after the induction phase, when newly diagnosed patients receive a series of 1 to 3 monthly anti-VEGF injections to bring the disease under control.)

Using those parameters, the group calculated personalized-regimen spending by Medicare to be $9.3 billion, $2 billion, and $2.8 billion for ranibizumab, bevacizumab, and aflibercept, respectively. To the fixed-regimen spending totals, OCT-guided, personalized-treatment regimens enabled Medicare to save $10.3 billion on anti-VEGF therapy costs for AMD from 2008 to 2015. Fewer injections of ranibizumab are responsible for 83% of the calculated savings, the authors wrote.

Actual Medicare spending was $6.5 billion for ranibizumab, $1.1 billion for bevacizumab, and $2.4 billion for aflibercept (for a total of $10 billion). In other words, the actual spend from Medicare was $4.1 billion (29%) less than the authors’ calculated personalized-regimen spending total. They concluded by noting investments in research “continues to yield billions of dollars in healthcare savings for patients and insurers. “


 1. Neely DC, Bray KJ, Huisingh CE, Clark ME, McGwin G, Owsley C. Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care. JAMA Ophthalmol. 2017;135(6):570-575. doi:10.1001/jamaophthalmol.2017.0830

2. Cruickshanks KJ, Nondahl DM, Johnson LJ, Dalton DS, Fisher ME, Huang G, Klein BE, Klein R, Schubert CR. Generational Differences in the 5-Year Incidence of Age-Related Macular Degeneration. JAMA Ophthalmol.2017;135(12):1417-1423. doi:10.1001/jamaophthalmol.2017.5001

3. Windsor MA, Sun SJJ, Frick KD, Swanson EA, Rosenfeld PJ, Huang D. Estimating Public and Patient Savings From Basic Research-A Study of Optical Coherence Tomography (OCT) in Managing Antiangiogenic Therapy. Am J Ophthalmol 2018;185:115-122.

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