Perelman School of Medicine at the University of Pennsylvania

Center for Preventive Ophthalmology and Biostatistics (CPOB)

Comparison of Age-Related Macular Degeneration Treatments Trials (CATT)

CATT logoClick here for a link to CATT Publications
Click here to link to CATT Slide sets and CATT Manual of Procedures (MOP)
Click here for a link to CATT Data Export Site

The Comparisons of Age-Related Macular Degeneration Treatments Trials (CATT) was a multi-centered randomized clinical trial to assess the relative safety and efficacy of two treatments for subfoveal neovascular Age-Related Macular Degeneration (AMD), a disease that usually causes severe irreversible vision loss. CATT was conducted in 44 clinical centers and was funded by the National Eye Institute.

The CPOB is home to both the CATT Coordinating Center and the Fundus Photograph Reading Center. The other resource centers are the Office of the Study Chair at Emory University and the Optical Coherence Tomography (OCT) Reading Center at Duke University.

Click here for additional information regarding the CATT Study from the website.

Click here for additional information regarding the CATT Study from the NEI website.


Age related macular degeneration (AMD) is the leading cause of severe vision loss in people over the age of 65 in the United States and other Western countries (Tielsch, 1994; Sommer, 1991; Leibowitz, 1980; Klein, 1992; Sorsby, 1966; Buch, 2001). More than 1.6 million people in the US currently have one or both eyes affected by the advanced stage of AMD (Friedman, 2002) and it is estimated that there are another 7 million individuals “at risk” (The Eye Diseases Prevalence Research Group 2004). Once advanced AMD occurs in one eye, the risk for developing advanced AMD in the second eye over a 5 year period is 43% (AREDS, 2001) and the impact is substantial; more than 230,000 people in the United States are believed to be legally blind due to AMD (Tielsch, 1994). In the US alone, the direct cost of illness associated with AMD is conservatively estimated at $10 billion annually. Because the incidence of AMD rises sharply with age, these numbers will multiply as the American population over the age of 65 increases. Projections by the US Census Bureau indicate the US population aged 65 years and older will increase 54% from 2000 to 2020 (US Census Bureau, 2002).

Most AMD-related blindness is attributable to neovascular form of the disease, known as choroidal neovascularization (CNV), which occurs when new, abnormal blood vessels develop in the macula. (The macula is responsible for central vision.) Treatments target these new vessels and try to prevent their development.

The CATT study was designed to evaluate the relative safety and efficacy of two drugs used to treat neovascular AMD on visual acuity and to evaluate how frequently the drugs should be administered.

In addition to determining which drug and treatment schedule is better in treating AMD, another important aspect of the CATT concerns the cost of these treatments. Using conservative estimates, the price differential between the treatments could be $26,800 per patient annually, yielding a savings to Medicare of up to $3 billion per year ($8.2 million per day)!

Treatments for Neovascular AMD Prior to CATT

The latest treatments for neovascular AMD are designed to stop the growth of and leakage from abnormal blood vessels. These drugs are referred to anti-angiogenic drugs. (The word “angiogenesis” means the development of new blood vessels.) Drug treatment can help slow down vision loss from AMD and in some cases improve sight. These drugs are injected into the vitreous of the eye, usually every 4-6 weeks.

Ranibizumab (Lucentis®) was the first anti-VEGF drug for treating neovascular AMD approved by the FDA in June 2006. The regime used in the clinical trials showing the effectiveness of ranibizumab was an intravitreal injection every month. Before ranibizumab was approved and widely available, many ophthalmologists began using an almost identical drug, known as bevacizumab, to treat neovascular AMD. Bevacizumab (Avastin®) is another anti-angiogenic drug that is approved by the FDA to treat certain cancers. This “off-label” use of bevacizumab appeared to offer promising results similar to that of ranibizumab, but there had not been a large, carefully controlled clinical trial to evaluate its effectiveness and safety for neovascular AMD.

The approval and availability of ranibizumab to treat neovascular AMD did not stop interest in bevacizumab because there are considerable cost differences in the two therapies. A ranibizumab treatment costs approximately $2,000 per dose while bevacizumab treatment for AMD costs approximately $50-$100. Considering that both drugs require multiple treatments, this cost differential is substantial.

In addition to the differences and similarities of the two drugs, the issue of dosing schedule was also of great interest. Widespread implementation of a fixed, every 4 week dosing schedule has obvious practical limitations and the cost of such repeated injections is considerable. Before CATT, no studies had addressed the question of whether a reduced dosing schedule is as effective as a fixed schedule of monthly injections. CATT was designed to do so.

Study Aims

CATT’s primary outcome measure was change in visual acuity at one year. Secondary outcomes include

  • Number of treatments
  • 3-line change in visual acuity (15 letters on ETDRS chart)
  • Change in subretinal and intraretinal fluid on OCT
  • Change in lesion size on fluorescein angiography
  • Incidence of complications of treatment (endophthalmitis, retinal detachment, cataract, uveitis)
  • Cost of treatment

CATT Study Design

CATT Participants:

Between February 2008 through December 2009, CATT enrolled 1208 participants at 44 clinical centers. To be eligible, subjects must have been aged 50 and older with subfoveal CNV secondary to AMD in at least one eye and visual acuity between 20/40 and 20/320, inclusive. The study eye must not have had any previous treatment for AMD. Click here to see complete eligibility requirements.

All participants were assigned randomly to one of four treatment groups and completed monthly visits for 24 months.

  1. 0.50 mg. ranibizumab every 28 days (ranibizumab monthly) for 1 year; at 1 year, re-randomization to ranibizumab every 4 weeks or to variable dosing.
  2. 1.25 mg. bevacizumab every 28 days (bevacizumab monthly) for 1 year; at 1 year, re-randomization to ranibizumab every 4 weeks or to variable dosing.
  3. 0.50 mg. ranibizumab only when signs of active neovascularization were present (ranibizumab as needed)
  4. 1.25 mg. bevacizumab only when signs of active neovascularization were present (bevacizumab as needed).

Study Visits

All CATT participants received a study treatment at their initial visit and had monthly study visits thereafter for two years. Those assigned to the fixed monthly dosing groups received treatment at every visit. Those assigned to variable dosing groups were evaluated for treatment at every visit. If lesion activity was present, the participant received a study treatment.

Study visit procedures included established tests of visual acuity conducted by examiners masked to the treatment assignment, an examination by a CATT ophthalmologist, and retinal photographs and OCTs that were assessed by masked graders in centralized reading centers. The images provided a clinical picture of the severity of AMD.. Click here to view all procedures that occurred during study visits.

CATT One-Year Results

In April, 2011, the one-year results were published in the New England Journal of Medicine. After one year, ranibizumab and bevacizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. The proportion of participants who did not have a decrease in visual acuity of at least 15 letters was the same in all groups, as were the proportion of those who gained at least 15 letters. For more details on the one-year results, click here.

CATT Two-Year Results

In 2012, the two-year CATT results were published in the journal Ophthalmology. After 2 years, ranibizumab and bevacizumab had similar effects on visual acuity. At two years, visual acuity with monthly treatment was slightly better (by about half of a line on an eye chart) than with as-needed dosing, regardless of the drug. 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. 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.

Serious adverse events (SAEs) occurred at a 40% for patients receiving bevacizumab and a 32% rate for patients receiving ranibizumab. Although this group had a higher rate of SAEs, they were distributed across many different conditions, most of which are not associated with bevacizumab when evaluated in cancer clinical trials, in which the drug was administered at 500 times the dose used for AMD. Fewer doses were associated with a higher rate of SAEs, which is not a typical dose-response relationship. For more details on results at 2-years, click here.  For additional information on serious adverse events associated with bevacizumab or ranibizumab for AMD, click here.

CATT Follow-Up Study

In 2013, the National Eye Institute awarded funds to the CATT Study group to invite all living CATT participants to return to the CATT Clinical Centers for an additional visit. Returning participants underwent a dilated eye examination, refraction and VA measurement, and imaging, which followed the same protocols used during the original CATT trial. Participants signed a medical records release if they had received care for AMD from outside the CATT clinical center and were interviewed about treatment to either eye, visits to ophthalmologists and serious medical events since their last visit in the clinical trial.

In 2016, the journal Ophthalmology published the results of the CATT Follow-up Study. Among the 914 living patients, visual acuity was obtained on 647 patients (71%), with an average follow-up of 5.5 years. The vision gains obtained during the first 2 years of the trial were not maintained at 5 years; mean visual acuity declined to 3 letters worse than at baseline and 11 letters worse than at 2 years. However, half the eyes had visual acuity 20/40 or better, confirming the benefit of anti-VEGF treatment for neovascular AMD. In 36% of eyes, there was an abnormally thin retina at the foveal center. Between 2 and 5 years, the group originally assigned to ranibizumab for 2 years lost more visual than the bevacizumab group (−4 letters; p=0.008). Otherwise, there were no statistically significant differences in VA or morphological outcomes between drug or regimen groups. For more information, click here.

CATT Publications

The CATT trial has resulted in 41 papers and 10 editorials/commentaries published in major medical journals. An additional paper is in press and work proceeds on 10 more. Click here for a list of CATT Study publications.

CPOB’s Role in CATT

CPOB staff members support both the Coordinating Center and the Photograph Reading Center for the CATT study. Click on the links to learn more about the services of the Coordinating Center and the Scheie Image Reading Center.

References Cited

Age-Related Eye Disease Study Research Group. A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss: AREDS Report No. 8. Arch Ophthalmol 2001;119:1417-1436.

Buch H, Vinding T, Nielsen NV. Prevalence and causes of visual impairment according to World Health Organization and United States criteria in an aged, urban Scandinavian population: the Copenhagen City Eye Study. Ophthalmology. 2001; 108:2347-57.

Friedman DS: Vision Problems in the U.S. Prevalence of Adult Vision Impairment and Age-Related Eye Disease in America. Prevent Blindness America, Schaumburg, IL:2002.

Klein R, Klein BEK, Linton KLP: Prevalence of age-related maculopathy: The Beaver Dam Eye Study. Ophthalmology 1992; 99:933-945.

Leibowitz HM, Krueger DE, Maunder LR, et al: The Framingham Eye Study Monograph. Survey Ophthalmol 1980; 24:335-610.

Sommer A, Tielsch JM, Katz J, et al: Racial differences in the cause-specific prevalence of blindness in East Baltimore. N Engl J Med 1991; 14:1412-1417.

Sorsby A: Reports on public health and medical subjects. No. 114. London: Her Majesty's Stationery Office, 1966.

The Eye Disease Prevalence Research Group. Prevalence of Age-related Macular Degeneration in the United States. Arch Ophthalmol 2004; 122:564-572.

Tielsch JM: Vision Problems in the U.S. Prevent Blindness America, Schaumburg, IL:1994.

United States Census Bureau. Projections of the Total Resident Population by 5-year Age Groups and Sex with Special Age Categories: Middle Series, 1999 to 2020 and 2016 to 2020. Click here for link to US Census Bureau.

CATT Slide sets and Manual of Procedures

Click here to link to Baseline predictors of visual acuity outcomes, Ying, et al.

Click here to link to Incidence of CNV in the Fellow Eye, Maguire, et al.

Click here to link to Macular Morphology and Visual Acuity in CATT, Jaffe, et al.

Click here to link to Pharmacogenetics of Anti-VEGFs in CATT, Hagstrom, et al.

Click here to link to CATT Manual of Procedures