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Vision-Related Function in Patients with Age-Related Macular Degeneration


Ivan J. Suñer, MD
Retina Associates of Florida
Tampa, FL


doctorNeovascular (wet) age-related macular degeneration (AMD) typically affects central vision. As a result, it poses a threat to patients' ability to function independently and pursue the activities they enjoy. Specifically, neovascular AMD threatens the ability to drive, read, pay bills, and recognize faces. Traditionally, the primary outcome measure in clinical trials evaluating treatments for neovascular AMD is best-corrected visual acuity in the study eye. While this parameter provides a measurable, objective outcome, it does not always correlate with the patient's visual function. We sometimes have difficulty understanding how our patients "can't see" even though their vision has improved to 20/25 after treatment; conversely, we may struggle to explain how patients are "seeing much better" despite measuring 20/100 before and after treatment. These scenarios illustrate that measures of visual acuity do not always fully capture the entirety of visual function. While several studies have demonstrated that visual acuity is correlated with patient-reported vision-related function,1,2 the results of these assessments are not always interchangeable. Rather, they should be viewed as complementary assessments of vision.


Another critical distinction is that while visual acuity is an objective assessment of monocular function, measures of vision-related function are inherently subjective assessments of binocular function. As a result, several studies have demonstrated that vision-related function is generally driven by the better-seeing eye.3


The National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) was developed to measure a patient's subjective assessment of vision-related function.4 It has been validated for multiple eye diseases including AMD, cataracts, diabetic retinopathy, primary open-angle glaucoma. The NEI VFQ-25 is the best-studied vision-related function instrument in AMD.5 It is scored as an overall or composite score, as well as twelve subscales. The most relevant subscales in AMD are the near activity, distance activity, and driving scales, as these pertain to central vision function. The NEI VFQ-25 also includes other subscales that pertain directly to vision function such as general vision, color vision, peripheral vision, and ocular pain. Furthermore, it includes general function subscales such as dependency, general health, role difficulties, mental health, and social functioning.


Vision-Related Function in Clinical Trials
The ANCHOR and MARINA trials were the first large, randomized, masked, controlled clinical trials to demonstrate improvement in vision-related function with pharmacologic treatment. The ANCHOR trial compared monthly intravitreal injections of ranibizumab to another active treatment, namely photodynamic therapy with verteporfin, while the MARINA trial compared monthly intravitreal injections of ranibizumab to sham injections.6,7


In ANCHOR, at 12 months, patients treated with ranibizumab (0.5 mg) had a mean improvement in composite scores of 8.1 as compared to a mean improvement of 2.2 in the verteporfin group (p < 0.001).8 There was also a significant difference in the prespecified subscales of near activities, distance activities, and vision-specific dependency. Interestingly, both groups showed improvement in NEI-VFQ scores despite a disparity in the visual acuity results (mean visual acuity increased by 11.3 letters in the ranibizumab group, and decreased by 9.5 letters in the verteporfin group).6 We can speculate whether this was a treatment effect or a biologic effect. Perhaps verteporfin provides "better quality" of vision despite a loss in measured visual acuity as a result of drying the macula, thereby reducing metamorphopsia or other visually-disturbing effects of active leakage.


In MARINA, at 12 months, patients treated with ranibizumab (0.5 mg) had a mean improvement in NEI VFQ-25 composite scores of 5.6 versus a mean decrease of 2.8 in the sham-injection group (p < 0.001).9 The prespecified subscales also demonstrated a similar trend. In MARINA, the ranibizumab group had a mean increase in visual acuity of 7.2 letters as compared with a mean decrease of 10.4 letters in the sham-injection group.7


These are remarkable results in the context that there was significant improvement in vision-related function even though the majority of the patients were being treated in their worse-seeing eye (75% in ANCHOR, 54% in MARINA).8,9


Vision-related function is a complementary assessment to visual acuity. While visual acuity provides an objective assessment of the treated eye, instruments such as the NEI VFQ-25 provides information about the individual's overall binocular visual function. While there is a general correlation of improvement in NEI VFQ-25 scores with improvement in visual acuity, the NEI VFQ-25 provides an assessment of the quality of patients' overall visual function as it pertains to patients' visual needs and expectations. It also gives us tangible information regarding the overall impact of therapies for AMD on the vision-specific quality of life and function of our patients with AMD.



    1. Miskala PH, Bass EB, Bressler NM, et al. Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: quality of life findings: SST report No. 12. Ophthalmology. 2004;111:1981-1992.
    2. Cahill MT, Stinnett SS, Banks AD, et al. Quality of life after macular translocation with 360 degrees peripheral retinectomy for age-related macular degeneration. Ophthalmology. 2005;112:144-151.
    3. Linder M, Chang TS, Scott IU, et al. Validity of the visual function index (VF-14) in patients with retinal disease. Arch Ophthalmol. 1999;117:1611-1616.
    4. Mangione CM, Lee PP, Gutierrez PR, et al. Development of the 25-item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol. 2001;119:1050-1058.
    5. Suñer IJ, Matchar D, Lee PP. Measuring Quality of Life for Patients with Age-Related Macular Degeneration. Medicare Coverage Advisory Committee Technology Assessment. 2006..
    6. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-1444.
    7. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419-1431.
    8. Bressler NM, Chang TS, Fine JT, Dolan CM, Ward J. Quality of life outcomes improved more often with ranibizumab than photodynamic therapy in a randomized clinical trial. Arch Ophthalmol. 2009;127:13-21.
    9. Chang TS, Bressler NM, Fine JT, Dolan CM, Ward J, Klesert TR. Improved vision-related function after ranibizumab treatment of neovascular AMD: results of a randomized clinical trial. Arch Ophthalmol. 2007;125:1460-1469.


Ingrid U. Scott, MD, MPH,  Editor

Professor of Ophthalmology and
Public Health Sciences,
Penn State College of Medicine


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