Realizing the Potential of OCT
Where does optical coherence tomography fit into AMD treatment decision-making and outcomes assessment? A clinical investigator weighs in.
PETER K. KAISER, MD

Optical coherence tomography (OCT), now used as an adjunct to fluorescein angiography (FA), has the potential to become an important imaging resource for evaluating and treating age-related macular degeneration (AMD). There are no published studies on using OCT alone or as the main imaging modality in AMD treatment. However, its inclusion in several large-scale clinical trials of photodynamic therapy (PDT) and anti-angiogenesis drugs affords us the opportunity to gather evidence of its utility.

The Cole Eye Institute of the Cleveland Clinic where I practice has served as a site for several large-scale, randomized clinical trials and also as an OCT reading center for several ongoing AMD clinical trials. Our experience has revealed the limitations of FA in quantifying AMD-related retinal neovascular changes. Moreover, it shows how OCT may serve as an important adjunct for the diagnosis, treatment and follow-up of this debilitating condition.

As a clinical investigator and supervisor of an image-reading center in clinical trials of new therapies, I've drawn on my experience to supplement the published literature and discuss the most likely future direction for OCT in the management of AMD.

This patient's fluorescein angiogram shows questionable leakage; but OCT reveals no subretinal fluid.

OCT VERSUS FA

Fluorescein angiography is the gold standard diagnostic imaging modality to detect the presence of choroidal neovascularization (CNV) in AMD. It is necessary for any laser-based AMD treatment, such as PDT or photocoagulation, as it will show precisely where to apply the laser to treat the leaking vessels. FA can define the location and lesion characteristics and can guide therapy, whereas OCT cannot.

However, most recent clinical studies of AMD include the use of OCT in the clinical protocols to quantify the effects of therapy on the CNV lesion and the retina in ways that FA cannot. It's important to note that these studies have not used OCT as the basis for treatment decisions; thus, we can't use OCT as a replacement for FA.

In the clinical trials of verteporfin (Visudyne) for PDT, researchers assessed treatment outcome primarily by FA.^1,2 We soon learned from those trials that often it was difficult to use FA to determine if treated neovascular membranes were leaking, staining, active or nonactive. Moreover, FA tells us whether or not a choroidal neovascular membrane is leaking, but it doesn't tell us how this leakage may be affecting the retina. Because of this, PDT treatments often were performed when leakage was equivocal on FA, based on the idea that no harm was being done. However, this approach may not be optimal, as some unrecognized damage to retinal structures could conceivably be occurring from repeated PDT. Minimizing treatments is usually best for the patient, and OCT may help determine which treated eyes have signs of persistent fluid, intra- or subretinal swelling or cystic formations that indicate active CNV requiring further treatment. We can detect these things on OCT.^3­5

OCT can help quantify the amount of leakage to evaluate for treatment. FA does not. In clinical practice, eyes that have questionable CNV leakage on FA are examined more closely using OCT to identify or rule out retinal thickening that would support the need for additional treatment of the CNV. Patients who show signs of leakage on OCT, for example, would likely derive additional benefit from PDT treatment. Patients who showed no signs of leakage on OCT likely would not benefit.

A retrospective study by Puliafito and coworkers⁵ established a grading system for using OCT to evaluate results of eyes treated for AMD with PDT, and demonstrated that OCT was a valuable supplement to the diagnostic information obtained by FA. Studies have shown that the findings of OCT can correlate with the results of PDT, lending support to this approach.^5,6

NEW AMD THERAPIES

New-generation AMD therapies that target the angiogenesis pathway will likely benefit from the diagnostic information provided by OCT. Anti-angiogenesis drugs, like the anti-VEGF inhibitors ranibizumab (Lucentis) and pegaptanib sodium (Macugen), have been shown to not only minimize CNV formation but also decrease blood vessel permeability and retinal swelling in animals and humans.^7,8

Again, the amount of fluid leakage cannot be quantified meaningfully using FA, but OCT very precisely measures macular volume and reliably tracks changes in retinal thickness over time.⁹ Even dramatic changes in retinal architecture sometimes go undetected by FA or other imaging modalities. OCT, on the other hand, can detect reductions in retinal thickness as small as 10 µm.¹⁰ Ultra high-resolution devices are being developed that can measure down to 3 µm.¹¹

With the arrival of anti-angiogenesis therapies for AMD, the categorization of CNV as classic or occult based on FA could become outdated. The only reason FA may be required is to ascertain that a CNV is present. These new drugs are injected intravitreally or, in the case of another anti-angiogenic drug, the steroid derivative anecortave acetate (Retaane), as a depot in posterior juxtascleral tissue, so the location and size of leaking vessels are not relevant to successful treatment. It's more important to accurately assess whether neovascular membranes are present and if so, whether they're being reduced after treatment. The type and location may not be as relevant as it was in the past when laser-based therapies were used. OCT gives us this information, and it does so in a noninvasive manner.

Intravenous fluorescein injection causes complications in 5% to 10% of patients, and these can potentially be serious.¹² OCT can be performed with no risk to the patient, and it also takes less time.

THE PRESENT AND FUTURE

Although I don't see OCT replacing FA, I believe it will soon become a standard imaging procedure for AMD patients. Currently, I use OCT to supplement FA interpretation, especially in making decisions about treatment with PDT. I see OCT taking a primary role in the future as we move away from laser-based, location-dependent treatments. The integration of simultaneous OCT and scanning laser ophthalmoscopy is also under investigation. The potential to both quantify and locate retinal pathology using a single instrument promises great benefits.

In the meantime, the lack of published data on OCT from randomized clinical trials of AMD treatment leaves practitioners without clear guidance on the benefits of this imaging modality. This should change in the near future with the completion of trials of new drugs, as well as continuing studies of PDT where OCT data is being collected and analyzed. When this data becomes available, our clinical impressions of OCT's value can be objectively validated.

Dr. Kaiser is an associate staff member at Cole Eye Institute, Cleveland Clinic Foundation in Cleveland

REFERENCES

1. Blinder KJ, Bradley S, Bressler NM, et al. Treatment of Age-related Macular Degeneration with Photodynamic Therapy study group; Verteporfin in Photodynamic Therapy study group. Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1. Am J Ophthalmol. 2003;136:407­418.

2. Barbazetto I, Burdan A, Bressler NM, et al; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study Group; Verteporfin in Photodynamic Therapy Study Group. Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin: fluorescein angiographic guidelines for evaluation and treatment -- TAP and VIP report No. 2. Arch Ophthalmol. 2003;121:1253­1268.

3. Hee MR, Izatt JA, Swanson EA, et al. Optical coherence tomography of the human retina. Arch Ophthalmol. 1995;113:325­332.

4. Schuman JS, Puliafito CA, Fujimoto JG, eds. Optical Coherence Tomography of Ocular Diseases, 2nd ed. Thorofare, NJ: Slack Incorporated; 2004.

5. Puliafito CA, Hee MR, Lin CP, et al. Imaging of macular diseases with optical coherence tomography. Ophthalmology. 1995;102:217­229.

6. Taban M, Boyer DS, Thomas EL, Taban M. Chronic central serous chorioretinopathy: photodynamic therapy. Am J Ophthalmol. 2004;137:1073­1080.

7. Heier JS. The VEGF antibody approach: the rhuFab Collaborative Trial. rhuFab V2 for the treatment of wet AMD. Paper presented at: Annual Meeting of the American Academy of Ophthalmology; November 17, 2003; Anaheim, CA.

8. Kaiser PK. Posterior juxtascleral depot of anecortave acetate for subfoveal CNV in AMD: 24-month outcomes. Paper presented at: Annual Meeting of the American Academy of Ophthalmology; November 17, 2003; Anaheim, CA.

9. Browning DJ. Interobserver variability in optical coherence tomography for macular edema. Am J Ophthalmol. 2004;137:1116­1117.

10. Voo I, Mavrofrides EC, Puliafito CA. Clinical applications of optical coherence tomography for the diagnosis and management of macular diseases. Ophthalmol Clin North Am. 2004;17:21­31.

11. Drexler W, Sattmann H, Hermann B, et al. Enhanced visualization of macular pathology with the use of ultrahigh-resolution optical coherence tomography. Arch Ophthalmol. 2003;121:695­706.

12. PDR for Ophthalmology. Montvale, NJ: Medical Economics Company, 2001; pp. 215-216.