Does age affect retinal drusen, pigmentary abnormalities, and overall macular degeneration? In the Beaver Dam Eye study, 4926 patients from age 43 to 68 were studied using stereoscopic color fundus photography to answer this question.
Overall, the Beaver Dam Eye study is a landmark trial because it demonstrated the association between AMD and age, and was one of the first large scale prevalence studies for the disease. This association was deemed a “substantial public health problem” that previously had not been realized.
In a world before anti-VEGF, what could we do for wet AMD? Prior to the use of anti-VEGF injections, treatment options for wet AMD were very limited. The TAP study sought to evaluate the efficacy of Verteporfin Photodynamic Therapy (PDT) in reducing vision loss in patients with subfoveal choroidal neovascularization (CNV) caused by AMD. Across two studies, 609 patients were randomized to treatment with verteporfin (n= 402) and placebo (n= 207) followed by laser light at 689 nm delivering 50 J/cm2.
Overall, the TAP trial is a landmark study that showed the efficacy and safety of PDT with verteporfin for treatment of CNV in classic wet AMD. And while this treatment is rarely used today due to the use of anti-VEGF medications that improve vision – not just slow vision loss – the TAP trial provided valuable information that impacted the practice of ophthalmology.
Take your vitamins every day, free of advanced AMD you’ll stay. The Age-Related Eye Diseases Study (AREDS) was designed to study the clinical course of age-related macular degeneration (AMD) and age-related cataract. It included two double-masked, placebo-controlled, randomized clinical trials to test the effect of a vitamin formulation (500 mg vitamin C, 400 IU vitamin E, 15 mg β-carotene, with or without 80 mg zinc and 2mg copper) on the progression of these two conditions. AREDS enrolled 4,757 people aged 55-80 years to the long-term multicenter study, following them for an average of 6.3 years.
AREDS was a landmark study because it confirmed the effectiveness of this popular antioxidant formulation in decreasing the progression of severe AMD in the high-risk elderly population. It also left more to follow with AREDS2.
If at first you don’t “fully” succeed, try, try again. While AREDS1 showed that an oral supplement decreased the risk of developing advanced AMD in 5 years by 25%, observational data suggested that other nutrients may offer an additional protective benefit. AREDS2 aimed to evaluate the safety and efficacy of adding the antioxidant carotenoids lutein and zeaxanthin (L+Z) and/or omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) in decreasing the risk of progressing to advanced AMD. The study also sought to determine the effect of reducing the amount of zinc in the AREDS oral supplement and omitting beta-carotene completely.
Together with AREDS1, which showed a 25% decrease in progression to advanced AMD, AREDS2 fine-tuned the notable vitamin formula by adding lutein and zeaxanthin and removing beta-carotene.
“I ran” to the MARINA to fight the wet AMD. The MARINA trial to sought to determine the treatability of neovascular age-related macular degeneration (nAMD) with ranibizumab, an anti-VEGF antibody. This trial selected 716 nAMD patients with minimally classic or occult choroidal neovascularization. Patients were randomized to three groups: sham injection (n= 238), intravitreal injection of 0.3 mg ranibizumab (n=238), and intravitreal injection of 0.5 mg ranibizumab (n=240); Verteporfin photodynamic therapy was allowed if the choroidal neovascularization in the study eye became predominantly classic.
Overall, the MARINA trial was a landmark study because it identified a biologic, ranibizumab, that could prevent vision loss and improve visual acuity for NAMD. In the larger context, the MARINA trial in conjunction with the ANCHOR trial were landmark studies which showed ranibizumab to be effective for different types of neovascularization in AMD. Not only did this trial prove efficacious treatment for nAMD, which had not previously had very successful options, but it also jumpstarted the potential use of anti-VEGF treatment for many other disorders.
Anchors aweigh! Say farewell to verteporfin and ahoy to ranibizumab. In this double-masked phase III clinical trial, ranibizumab, an anti-VEGF antibody, was compared with the standard of care of the time - verteporfin photodynamic therapy (PDT). 423 patients with age-related macular degeneration (AMD) with predominantly classic neovascularization (CNV) were randomized to receive either verteporfin PDT, or monthly intravitreal ranibizumab (0.3 mg or 0.5 mg) for 2 years.
Results of the ANCHOR trial confirmed the clinical benefit of ranibizumab found in the landmark MARINA study, and demonstrated that ranibizumab outperformed verteporfin PDT in all measures evaluated in AMD patients with predominantly classical CNV lesions. Together they were instrumental in altering clinical practice and providing new hope in patients with numerous retinal conditions.
An anti-VEGF a month keeps the ophthalmologist away, but which one? The CATT trials looked assess the relative safety and efficacy of two treatments for subfoveal neovascular Age-Related Macular Degeneration (AMD). Most AMD-related blindness is attributable to choroidal neovascularization and therefore anti-VEGF therapy treatment was a crucial development in the fight to improve visual outcomes. In the CATT trial, patients with AMD (n=1185) were randomized to receive either intraocular injections of ranibizumab or bevacizumab (a cheaper, off-label alternative) at either a monthly or as needed regimen. Those patients in the monthly arm of the trial were equally divided again after 1 year to either remain monthly or switch to as needed.
The CATT was the first multicenter and largest trial to compare bevacizumab to ranibizumab (the more expensive, yet standard of the time). This study was crucial to establish the differences and similarities of the two drugs, primarily the non-inferiority of bevacizumab on similar treatment frequencies.
Might perfect be the enemy of good…when it comes to subretinal fluid retention. In the 2019 FLUID Study, visual acuity was assessed in patients with neovascular age-related macular degeneration (nAMD) previously randomized to treatment with monthly ranibizumab 0.5mg until resolution of intraretinal fluid (IRF) only (tolerating 200 microns of SRF) (n=175) versus complete resolution of both IRF and subretinal fluid (SRF) (n=174) before extending treatment intervals.
Overall, the FLUID study is a landmark study because it showed that incomplete subretinal fluid resolution did not create significant differences in long-term visual acuity in patients with nAMD and demonstrated the need for fewer injections with longer maintenance intervals in its treatment.
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