Spectral-domain optical coherence tomography (OCT) has come a long way toward bringing invivo histological diagnosis into the clinic. Physicians can readily distinguish all the of layers of the retina and determine which ones are involved in a particular clinical presentation of macular disease. Despite this exquisite power, there is occasionally discrepancy between the microanatomy and visual function as observed by the physician and experienced by the patient. Visual acuity, the gold standard for judging clinical efficacy, measures only the retina's ability to resolve details with 100% contrast at fixation and often does not accurately reflect how the patient perceives vision in the real world. As a result, patients often report visual impressions that are at odds with the acuities measured in the exam lane.

The Spectral OCT/SLO system (Opko, Miami, FL) combines OCT and scanning laser ophthalmoscopy (SLO) to deliver microperimetry that tests visual sensitivity at the level of the retina, evaluating an area of the visual space broader than just fixation. It assesses the threshold sensitivities (in dB) across the expanse of the macula and thus provides a better picture of the subject's visual world. Taking advantage of one-to-one correspondence between the retinal surface localization captured by SLO and the in-depth detail of the OCT, the instrument can test specific areas of the macula, study their histologic appearance and evaluate how they change over time.

CASE 1: PARALLEL IMPROVEMENTS
A 75-year-old man receiving treatment with bevacizumab (Avastin, Genentech, Inc.) was imaged with the Spectral OCT/SLO. Visual acuity at month 16 was 20/150 and at month 17 was 20/80-2. Average central thickness in the OCT topographic map changed from 153 µm at month 16 to 137 µm in month 17 (Figure 1). When the different topography exams are compared by overlay and subtraction, there is a central area that shows mild reduction in retinal thickness. The microperimetry maps are compared and their overlay subtraction map is shown in Figure 2. Note the improvement in central sensitivity in the region corresponding to the retinal thickness decrease on the topography difference map (Figure 3).

CASE 2: PARALLEL DECOMPENSATION
A 77-year-old man receiving treatment with bevacizumab was imaged with the Spectral OCT/SLO. Visual acuity at month 15 was 20/50 and at month 19 was 20/70. Central thickness on the OCT topography maps changed from 258 µm at month 15 to 332 µm at month 19 (Figure 4). When the OCT topographic maps are compared by overlay and subtraction the average central area shows an increase in thickness (Figure 5). Note the decrease in central sensitivity in the region corresponding to the thickness increase on the topography map. Some of the thickness increase appears to be due to subretinal fluid accumulation, which may explain the susceptibility to change with treatment.

Microperimetry testing integrated within the OCT/SLO imaging system adds dimension to the description of the complex changes in retinal structure and function that occur with progression of disease. While additional factors such as vascularity and metabolic integrity are currently outside the scope of the technology, the ability to accurately test the visual integrity of the microanatomy advances the clinician one step further toward the understanding of macular changes and the impact of therapies.

CASE EXAMPLE 3: MIXED CHANGES
A 60-year-old man recovering slowly from epiretinal membrane stripping 1 year earlier was imaged with Spectral OCT/SLO. Visual acuity at month 15 was 20/60-2 and at month 8 was 20/40-2. Average central thickness on the topography map changes from 289 µm in month 15 to 312 µm at month 18 (Figure 7). When the topographic maps are compared by overlay and subtraction, there is a central area that shows reduction in thickness (Figure 8). Note the improvement in central sensitivity in the region corresponding to the thickness decrease on the topography map (Figure 9).

CONCLUSION
Utilizing the high-contrast imaging of the SLO and its high-speed tracking capabilities, serial testing is both reliable and reproducible. The enhanced speed and reproducibility of this technology has led to increasing consistency between anatomic form, as reflected in retinal thickness maps, and retinal function, as revealed by visual sensitivity maps of the microperimetry exam.

When disparities between thickness and function occur, examination of the OCT cross-sections for evidence of loss of layers due to vascular pathologies, atropic changes, or toxic effects of drugs such chloroquine, usually explains the source of the problem. Alternatively, the presence or resolution of subretinal fluid or the accumulation of fibrinous material or excess lipofuscin under the retina may explain unexpected visual loss with normal or minimally increased OCT thickness maps.

Richard Rosen, MD, is Director of Resident Training in at the New York Eye and Ear Infirmary in Manhattan. Dr. Rosen states that he is a member of the scientific advisory board of Opko/OTI. He can be reached via e-mail at rrosen@nyee.edu.