November 2013, Issue 63

Microperimetry and Retinal Sensitivity in the Management of Age-Related Macular Degeneration

Matthew Shulman, BA Yasir Jamal Sepah, MBBS Quan Dong Nguyen, MD, MSc Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center Omaha, Nebraska

Imaging technologies have become a key component in the management of age-related macular degeneration (AMD), documenting pathologies seen on clinical examination and illuminating often subtle changes in the morphology of the macula lutea and fovea. Optical coherence tomography (OCT), for example, can allow visualization of drusen between the retinal pigment epithelium and Bruch's membrane, which are associated with the "dry" (non-neovascular) form of AMD. Fluorescein angiography (FA) can image the choroidal and retinal vasculature, helping to identify the neovascularization and intraretinal or subretinal fluid accumulation that characterize the neovascular or "wet" form of AMD.¹

As a disease of progressive deterioration of the dense collection of photoreceptors in the macula and fovea, AMD involves not only the loss of photopic vision and visual acuity, but also the loss of retinal sensitivity.¹ To this effect, several recent studies have indicated that along with considering changes in structure, measuring and analyzing retinal sensitivity may be an important addition to the established set of imaging tools employed in the management of AMD. With the continued adoption of microperimetry (MP) devices in hospital-based clinics and private practices, incorporating retinal sensitivity may offer clinically important advantages for AMD management.

MP measures macular sensitivity while accounting for fixation pattern and stability, providing near-exact correlation between fundus disease and its associated functional defects.^2,3 The two commercially available MP devices include the Spectral OCT/SLO (OPKO/OTI, Miami, U.S.A), which combines both spectral-domain OCT and microperimetric imaging modalities, and the MP-1 Microperimeter (Nidek, Padua, Italy), which is solely an MP device. Because the technology does not permit oculomotor interference, it can provide a highly accurate topographic map of areas of retinal sensitivity loss, known as scotoma, correcting for any adaptive strategies that may align the eyeball such that images land on functional eccentric retinal areas rather than the damaged central field.⁴ Such "true" scotoma size, which refers to the physical area of reduced retinal sensitivity to light, measured with MP was found to be significantly larger than the "effective" scotoma size, the area of perceived visual field deficit, as measured with the macular grid test with automated perimetry.⁴

MP scores appear to correlate well with disruptions in the inner segment-outer segment (IS-OS) junctional layer. Because of this, MP may offer a more robust and sensitive assessment of central macular function in dry and wet AMD than measuring visual acuity, and may even be useful in early detection of macular dysfunction before significant visual acuity loss occurs.⁵ After analyzing 17 patients with dry AMD (23 eyes) and 26 patients with wet AMD (32 eyes), Rosen and colleagues found both mean retinal sensitivity and best-corrected visual acuity (BCVA) to be correlated strongly with IS-OS junctional layer integrity in the central fovea for both conditions; a lower MP score meant a greater likelihood of having an IS-OS junctional layer disruption at a given tested retinal location.⁵

While many patients with dry and wet AMD can maintain a BCVA of 20/40 or better for some time — even with near-total IS-OS junctional layer destruction (90% to 100%) — mean MP scores will remain high until IS-OS junctional layer disruption reaches only 60% to 70%, at which point retinal sensitivity declines sharply as indicated by lower mean scores.⁵ The clinician may take advantage of this predictive indicator by being able to detect earlier the loss of photoreceptors and macular function before the loss of visual acuity, which may suggest a specific treatment or monitoring regimen.

Employing MP along with OCT and visual acuity testing during follow-up visits for patients with wet AMD treated with therapies such as anti-vascular endothelial growth factor agents may be useful for assessing patients' progress. According to a retrospective study by Parravano and colleagues, patients treated with three injections of 0.5 mg ranibizumab one month apart experienced visual acuity improvements that leveled off after 6 months, while retinal sensitivity measured by MP improved until 24 months, suggesting gains in macular function that would not have been recognized with visual acuity and retinal thickness measurements alone.⁶

Because geographic atrophy (GA) lesions associated with dry AMD may progress during the course of treatment, it may be helpful to track changes in retinal sensitivity or fixation quality over time using MP. In a recent study by Meleth et al., microperimetric analysis was performed on the central 20° of the macula of eyes with GA every 6 months over 24 months. The investigators found that MP could detect an increase in the number of scotomatous (non-responding) points, which corresponded with GA lesion expansion from baseline.⁵ Further, the authors note that the mean sensitivity of macular areas outside the GA lesion declined as a function of time, and that perilesional points demonstrated a greater—and more rapid—decline in sensitivity than extralesional points further from the GA lesion border.⁵ MP was also used to measure time-dependent decline in fixation stability, which decreased by 11.9% within the central 2° circle, and 11.7% within the central 4° circle.⁵

Incorporating MP in the management of both dry and wet AMD — before a diagnosis is made, during the initial assessment, and throughout the course of treatment — may be an important addition to the armamentarium of the retina specialist. Retinal sensitivity measurements can offer a more complete and thorough assessment and complement an ophthalmologist's understanding of the functional changes that accompany the degeneration of the macula and fovea.

References:
1. Hageman GS, Gehrs K, Johnson LV, Anderson D, in Kolb H, Fernandez E, Nelson R, editors. Webvision: The Organization of the Retina and Visual System [Internet]. Age-Related Macular Degeneration (AMD). Salt Lake City: University of Utah Health Sciences Center; 1995-. 2008 Jan 01.
2. Carpineto P, Ciancaglini M, Di Antonio L, Gavalas C, Mastropasqua L. - Fundus microperimetry patterns of fixation in type 2 diabetic patients with diffuse macular edema. Retina. 2007 Jan;27(1):21-9.
3. Toonen F, Remky A, Janssen V, Wolf S, Reim M. Microperimetry in patients with central serous retinopathy. Ger J Ophthalmol. 1995 Sep;4(5):311-4.
4. Markowitz, SN. Scotoma size reduction as an adaptive strategy in age-related macular degeneration. Can J Ophthalmol. 2010 May;45(4):393-398.
5. Landa G, Su E, Garcia PM, Seiple WH, Rosen RB. Inner segment-outer segment junctional layer integrity and corresponding retinal sensitivity in dry and wet forms of age-related macular degeneration. Retina. 2011 Feb;31(2):364-70.
6. Parravano M, Oddone F, Tedeschi M, Schiano Lomoriello D, Chiaravalloti A, Perillo L, Boccassini B, Varano M. Retinal functional changes measured by microperimetry in neovascular age-related macular degeneration patients treated with ranibizumab: 24-month results. Retina. 2010 Jul-Aug;30(7):1017-24.
7. Meleth et al. Changes in retinal sensitivity in geographic atrophy progression as measured by microperimetry. Invest Ophthalmol Vis Sci. 2011 Feb 28;52(2): 1119-26.