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Will OCT Replace FA in AMD?
A discussion into managing patients with CNV.
RISHI SINGH, M.D. AND PETER K. KAISER, M.D.

The advent of optical coherence tomography (OCT) has heralded a new era in diagnosis and treatment of retinal disease. Optical coherence tomography is a noncontact, noninvasive, high-resolution imaging device that shines a low coherence laser onto the retina and detects backscattered light. This is converted into micron-resolution, cross-sectional images of the retina within seconds and further analysis can be conducted in the computer to create 3D retinal maps and retinal thickness measurements. It has already shown its benefits in the detection of retinal edema in diabetic and uveitis patients.1-3

A new and exciting use for OCT is the diagnosis and management of wet AMD. Choroidal neovascularization (CNV) in AMD is the leading cause of visual loss in Western nations. Numerous studies have recently emerged on the use of OCT in this category of patients both in the detection and classification of lesion and in the guidelines for follow-up and retreatment of patients.4-6 The purpose of this article is to review the current literature on OCT use in AMD and to address whether OCT could conceivably replace fluorescein angiography (FA) in the diagnosis and management of AMD.

Initial Evaluation and Lesion Classification

The evolution of classification of neovascular AMD began in the Macular Photocoagulation Study (MPS) for choroidal neovascular membranes.7,8 In the MPS, the classification of neovascular AMD with CNV was based strictly on FA. During these trials, the terms classic and occult CNV were defined. The protocol stipulated that the CNV lesion had to be well demarcated (classic). A classic CNV is an area of bright, often well-demarcated, hyperfluorescence in the early phase of the angiogram, with progressive leakage of dye in the overlying subsensory retinal space during the late phases of the angiogram that obscure the margins. Occult neovascularization consists of CNV that has indistinct and often poorly defined boundaries on FA with less early leakage and irregular or stippled hyperfluorescence in late views of the angiogram. It can also have only late leakage of undetermined origins. Subsequent trials such as the Treatment in Age Related Macular Degeneration (TAP) and the Verteporfin in Photodynamic study (VIP) also examined the lesion leakage pattern, size and location for treatment.

Initial work with OCT has suggested that it was possible to separate classic from occult lesions. Classic membranes are often discrete subretinal lesions in the majority of cases while occult membranes were not.9 Recently, Sandhu and colleagues assessed the diagnostic accuracy of OCT with and without color photograph in predicting FA.10 Age-related macular degeneration lesions were classified as classic, occult, serious pigment epithelial detachments, and no neovascular complex seen based on specific OCT findings. The study found that OCT alone carried a sensitivity of 96.4%, but a specificity of 66.0%. When stereo fundus images were added, the sensitivity was 94% and the specificity improved to 89.4%. When detecting classic neovascular complexes with OCT alone, sensitivity and specificity were only 78.6% and 82.7%, respectively. Optical coherence tomography proved effective in detecting the presence of a potentially treatable lesion, but it failed at identifying the exact components. An OCT alone would have resulted in far too many not receiving appropriate treatments and far too many patients receiving treatments when it was unnecessary and thus OCT cannot supplant FA in this regard. However, OCT did show promise in the screening and prioritization of AMD patients for FA.

Follow-up and Retreatment

The decision for retreatment after photodynamic therapy (PDT) is based upon fluorescein angiogram findings detailed in the TAP study. However, recent studies have highlighted the significant variability amongst observers in interpretation of angiograms after PDT treatment.11 Adding to the confusion, fibrovascular tissue after treatment can remain hyperfluorescent in late frames allowing for misinterpretation. Furthermore, true retinal leakage cannot be quantified on angiography to compare one visit to the next.

The use of OCT in guiding retreatment has met with significant success. Salinas-Alaman and colleagues confirmed that OCT had good sensitivity in determining activity (95.65%), but moderate specificity (59.01%). Optical coherence tomography reliably documented decreases in macular thickness in response to therapy.4 In a similar study, Krebs and colleagues found that retreatments were reduced when activity of the membranes was diagnosed with angiogram and OCT vs. angiography alone (2.4 vs. 4.0 treatments).12 As PDT and antiantigenic therapies are quite expensive, costs of total treatment could be reduced because less retreatments would be necessary.

However, recent studies have highlighted the significant drawbacks of OCT evaluation of AMD. Eter and colleagues highlighted some patients that had angiographic leakage with no attributable OCT changes.13 Optical coherence tomography also had difficulty in defining the neovascular membrane when located underneath serous pigment epithelial detachments.4 Significant controversy in the literature still exists regarding whether OCT characteristics, such as the presence of cystoid edema can define active disease.13 Furthermore, the imaging of neovascular membranes is still limited by the penetration and poor spatial resolution of this evolving technology. Therefore, angiography in conjunction with OCT will likely result in the greatest sensitivity and specificity when determining which patients to retreat with PDT.

In contrast to PDT, the recent advent of antiangiogenesis drugs such as pegaptanib sodium and bevacizumab occurred during the era of OCT use. Given the injection frequency of every 4 to 6 weeks and the side effects and time needed for angiography, many clinicians have adopted the use of OCT for the interval evaluations. Macular thickness, the presence of CME, intraretinal and subretinal fluid and sub-RPE fluid can all be used as an indirect measurement of CNV activity and can be followed reliably with low interobserver variability.12 However, it is important to remember that the clinical studies did not use OCT for retreatment decisions and all patients were retreated irrespective of clinical picture.14 Only with additional studies will the utility of using OCT in follow-up evaluations of antiangiogenic drugs be determined. Until then, angiography is still vital for evaluating new progression of disease when on therapy or for the final evaluation before terminating treatment.

Conclusions

The use of optical coherence tomography in the evaluation and treatment of AMD has skyrocketed over the past few years. Numerous studies have been undertaken to determine if this modality will eventually usurp fluorescein angiography in the management of AMD. The current literature suggests that OCT can serve as a useful adjunctive test to FA especially in cases where lesion activity is questioned. Further randomized trials are needed to retrofit the treatment and retreatment criteria established in the TAP trial to include OCT evaluation in the future.

Peter K. Kaiser, M.D., is director, Digital Optical Coherence Tomography Reading Center (DOCTR), Cole Eye Institute. He can be reached at pkkaiser@aol.com.

Rishi P. Singh, M.D., is a Vitreo-retinal Fellow, Retina Service, Cole Eye Institute. He can be reached at drrishisingh@yahoo.com. Neither author has financial interest in the information contained in this article.

References

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