12.3  Use of OCT When Compared with Photography: Beyond Diagnostic Accuracy

Summary for the Clinician

■Clinician suspecting CSME requiring treatment can use Stratus central subfield thickness values below 250 mm to rule out CSME, and values above 300 mm to rule in CSME. Thickness values between 250 and 300 mm still suggest CSME, but treatment decision should be based, even more than usual, on patient’s symptoms and preferences as well as on other clinical features that an ophthalmologist may use to decide on the potential treatment outcome.

12.2.4  Do We Expect Any Differences in Retinal Thickness Thresholds Adopted to Define­

CSME Using Spectral-Domain Compared with Time-Domain OCTs?

An upward adjustment of the thresholds suggested earlier, obtained with the Stratus OCT, may prove necessary for Cirrus and possibly other spectral-domain OCTs. In fact, Wolf-Schnurrbusc et al. [19] found that six spectraldomain OCTs yielded central retinal thickness measurements of 32–77 mm larger when compared with the Stratus OCT in 20 normal subjects, and Forooghian et al. [20] found that central subfield measurements with the Cirrus OCT were larger by 53 mm than the Stratus OCT in 33 patients with DME. Other published research on patients with various retinal conditions suggested similar differences between Stratus and Cirrus OCTs [21–23]. Given the published research, 50 mm should be added to the thresholds suggested earlier to rule in/out CSME when using a spectral-domain OCT, i.e., values below 300 mm would suggest the absence of CSME and values above 350 mm presence of CSME using spectral-domain devices, but confirmatory research is needed for each device. On comparing Stratus and Cirrus OCTs in 25 normal and 25 diabetic subjects, we found that such an overestimate was a function of retinal thickness (unpublished data): a 50 mm was found in normal subjects when compared with no estimated difference at about 550 mm thickness in CSME patients using a linear regression model.

Summary for the Clinician

■Add 50 mm to the thresholds suggested earlier when using Cirrus (and possibly other spectral domain) OCT (no CSME: below 300 mm; CSME: above 350 mm); confirmatory research is needed on this correction factor for each spectral-domain device.

12.3  Use of OCT When Compared with

Photography: Beyond Diagnostic Accuracy

12.3.1  Establishing a Baseline Measure

to Monitor Response in People who

Are Treated for CSME Rather than Simply Assessing its Presence or Absence

Given that OCT is effective to diagnose CSME, its adoption to monitor treatment response seems straightforward. The fact that OCT provides a continuous measure of thickness makes the difference with respect to FP/FB for this purpose. However, while the ETDRS study gave guidance on decision about further photocoagulation based on the presence or absence of CSME, such information is limited regarding the value of, say, a reduction from 400 to 300 mm in a person with diabetic macular thickening a few weeks after antiVEGF injection, to decide about retreatment, which is an issue in ongoing research. Good-quality research on diagnosis–treatment interaction is far less common than that on accuracy, and large multicenter randomized controlled studies designed to compare the diagnostic strategies as a guide to treatment are needed, as summarized in a recently published methodological article [24].

Three aspects should be considered to move beyond diagnostic accuracy. First, a change in measurement well above the instrument reliability should be considered (see Appendix), but this is no longer a problem given the highly reliable OCTs. Second, we should use the diagnostic predictive research based on relatively small (<100 patients), single center cohort studies investigating several predictors of prognosis or treatment outcome, with caution. The results of these studies might not be generalizable to our clinics and would better need confirmation from independent studies. Furthermore, several predictors are typically tested against change in vision in such studies, and there is a high risk of chance findings, especially close to the conventional limits of statistical significance of (p-value 0.05 to 0.01). A few of such studies will be briefly presented in the last paragraph.

Lastly, until research from large multicenter studies will clarify the predictive/prognostic role of OCT in patients with DME, especially regarding treatment response and monitoring, in the following chapter, we review some leading research on the relationship between change in OCT and visual acuity, research conducted by the Diabetic Retinopathy Clinical Research Network [25, 26].

12.3.2  Potential Validity of OCT for Monitoring

Treatment Response

A benefit in diagnosing the presence or absence of CSME exists because this has been linked to prognosis (about

30% risk of visual loss in 3 years) and the benefit obtained with laser photocoagulation. Both these types of information were obtained from ETDRS studies conducted many years ago [5, 27].

12  Construct validity of OCT, specifically its cross-sec- tional and longitudinal association with visual acuity, has been investigated by the Diabetic Retinopathy Clinical Research Network in patients with CSME included in a randomized study on laser techniques [25]. They found that the cross-sectional correlation of OCT retinal thickness with visual acuity was moderate (correlation coefficient = 0.52), such that the center point thickness alone explains about 27% of the variance of visual acuity. They also found that the longitudinal correlation was modest, as the change in the center point retinal thickness correlation with change in visual acuity at 12 months was 0.40. The authors also provided reference to other studies that obtained similar conclusions. About 7% of patients with retinal thickening gained vision and 26% lost vision despite the fact that thickness decreased at 12 months. Furthermore, the authors could not demonstrate whether considering a lag in this association could improve the correlation, because it did not increase using change in the thickness that occurred months before. This means that OCT retinal thickness still remains the strongest known predictor of visual acuity in patients with DME, but it is not all we need and cannot be a substitute for visual acuity measurement [25].

A follow-up paper on the same cohort re-assessed the correlation of thickness and visual acuity comparing OCT with FP using a seven step ETDRS photographic severity scale of DME [26]. They found a substantial correlation between OCT and FP at baseline (0.67), and a moderate correlation (about 0.5) both cross-sectionally at 12 months and longitudinally (thickness change). Regarding the correlation with visual acuity, OCT did slightly better than FP at baseline (0.57 vs. 0.47, respectively), but FP did worse both at 12 months and considering change (0.53–0.48 vs. 0.29–0.27, respectively). This confirms the expectation that OCT is better than FP to monitor thickness change in DME, although vision is related to factors other than retinal thickness alone.

Summary for the Clinician

■Retinal-thickness measurement should not be a surrogate for visual acuity measurement in patients with DMO.

12.3.3  Candidate Predictors of Visual Outcome

Using OCT in Patients with DME

Many other findings are available using OCT in patients with DMO. The diagnostic and predictive role of these features has been mainly studied in case series, and should be considered with caution. The following is a brief description of a series of examples found by inspecting 383 titles retrieved using the key words DME and OCT on PubMed in May 2009.

■The integrity of the photoreceptors’ inner and outer layers was associated with visual improvement after vitrectomy for DME in 37 eyes [28].

■The diffuse retinal thickening OCT pattern was associated with a greater reduction in retinal thickening and better visual acuity improvement than the cystoids macular edema or vitreomacular interface abnormalities patterns (see Fig. 12.1) in 70 eyes of 45 patients with CSME, receiving photocoagulation [29].

■Subclinical macular edema, i.e., thickening detected with OCT but not with FP/FB, progressed to CSME in 31% of 153 patients, but OCT thickness increased in 13% of cases and decreased in 11% of cases [30]; according to us, this may be partly due to variability of judgment using FP/FB.

Other candidate features have been investigated within randomized clinical trials, such as:

■Posterior vitreous detachment (PVD) is more common after intravitreal triamcinolone than laser treatment for diffuse DME in 88 consecutive patients in 1 year; eyes with PVD had thinner retina but not better vision [31].

Summary for the Clinician

■OCT-based predictors of outcome after photocoagulation, vitrectomy, and intravitreal triamcinolone have been proposed and the prognosis of cases with subclinical macular edema (i.e., thickening found using OCT, but not found using FP/FB) have been studied mainly in case series and need further investigation.