Retina - AMD

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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. 

Key Points:

• Smoking and hypertension were found to be associated with AMD and suggest modifiable factors that could reduce the risk of AMD progression.
• Long-term treatment with AREDS supplements reduced the risk of progression from moderate to advanced AMD by 25%, and reduced odds of severe vision loss by 27%
• Among participants with no AMD or only early-stage AMD, there was no measurable benefit
• AREDS vitamin supplements did not reduce the development of lens opacities 

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. 

Key Points:

• No statistically significant reduction in disease progression was found in the groups assigned to take L+Z and/or omega-3 LCPUFAs in addition to the AREDS supplement
• No statistically significant reduction in disease progression was found with differing doses or zinc or with omission of beta-carotene.
• Significantly more cases of lung cancer occurred in patients who had history of smoking cigarettes and were taking beta-carotene (2%) versus those not taking beta carotene (0.9%); substituting beta-carotene for L+Z is appropriate

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.

Trick or treat? While eyeball injections and lasers give off haunted house vibes, patients may be in for a treat! The DRCR I evaluated the safety and efficacy of intravitreal ranibizumab with prompt or deferred laser and intravitreal triamcinolone with laser as compared to laser alone for the treatment of diabetic macular edema over 1 year.

Key Points:

• Regardless of laser timeline, ranibizumab treatment led to significantly improved visual acuity
• Treatment with either ranibizumab or triamcinolone in addition to laser led to a decrease in mean central subfield thickness on OCT compared to laser alone
• While ranibizumab may uncommonly lead to retinal detachments or endophthalmitis secondary to injection, it is an overall safe treatment option  

DRCR I demonstrated that treating patients with intravitreal ranibizumab + prompt or deferred laser is a safe and efficacious option to improve visual acuity and decrease central subfield thickness in patients with diabetic macular edema. This study introduced anti-VEGF agents as a leading option for the treatment of diabetic macular edema.

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. 

Key Points:  

• Ranibizumab and bevacizumab had similar effects on visual acuity (mean increase in letters of visual acuity from baseline was 8.8 in the ranibizumab-monthly group, 7.8 in the bevacizumab-monthly group, 6.7 in the ranibizumab-as-needed group, and 5.0 in the bevacizumab-as-needed group)
• Switching to as-needed treatment after one year of monthly treatment yielded outcomes nearly equal to those obtained with as-needed treatment for the full two years, with the mean number of injections was 5.0 for ranibizumab-treated patients and 5.8 for bevacizumab-treated patients
• There were no differences between the two drugs in rates of death or arteriothrombotic events, which are sometimes associated with systemic anti-VEGF treatment for cancer

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.