Current Research

6 Normal - retinal thicknessThe core research of EQUATΘR is to combine quantitative analysis with modern ocular imaging technologies to provide reliable measures of the activity of the disease and any cumulative damage. We are applying the principles of the techniques to all the major signs of inflammation within the eye.

A clear example of the value of this technique is in the measurement of vitreous haze. Vitreous haze (cloudiness of the central gel of the eye) is a valuable sign of inflammation, but the clinical score (the NEI Vitreous Haze Score)1 has a number of major problems. This limits its usefulness and reliability in both clinical practice and as an outcome measure for clinical trials.2

First Use of OCT to Measure Vitreous Haze – A Case Example

Screen Shot 2015-06-21 at 08.00.51In our proof-of-concept study we presented data from 60 patients comprising groups with uveitis with varying degrees of vitreous haze, uveitis with no vitreous haze, and non-uveitic patients.3 Among other parameters, the presence and severity of vitreous haze was classified according to the NIE Vitreous Haze Score. SD-OCT images (Spectralis, Heidelberg) were taken on a standard macula-focussed setting, and analyzed using custom software (OCTOR). This software provided an “absolute” measurement of vitreous signal intensity, which was then compared to that of the retinal pigment epithelium (RPE), generating an optical density ratio with arbitrary units (“VIT/RPE-Relative Intensity”).

In this study we found that the VIT/RPE-Relative Intensity was significantly higher in uveitic eyes with known vitreous haze (0.150) than in uveitic eyes without haze or in healthy controls (0.0767, p=0.0001). Importantly VIT/RPE-Relative intensity positively correlated with clinical vitreous haze scores (r=0.566, p=0.0001). Other ocular characteristics of inflammation also correlated with VIT/RPE-Relative Intensity including AC cells (r=0.613, p=0.0001) and AC flare (r=0.385, p=0.003). Importantly in the context of developing a tool that is objective and reliable, measurement of VIT/RPE-Relative Intensity showed a good degree of inter-grader reproducibility (95% limits of agreement: -0.019 to 0.016).

Screen Shot 2015-06-21 at 08.01.20

Why It Matters

This study was the first to demonstrate proof-of-concept that OCT-derived measurements of vitreous signal intensity may be useful as an outcome measure in patients with uveitis. This is an exciting advance since these measures may serve as an objective, quantitative disease activity endpoint, with the potential to improve the “signal:noise” ratio of clinical trials in this area. This would enable smaller studies for the same level of statistical power, with cost and feasibility benefits. The implications for clinical practice may be similarly profound.

We have gone on to develop a pilot automated system that can achieve these measurements in a matter of seconds.3 Incorporation of automated vitreous analysis in commercial OCT systems would greatly facilitate monitoring and retreatment of patients with uveitis in clinical practice.

The Future

Since this initial study we are continuing to build on this work through the establishment of the EQUATΘR consortium. EQUATΘR is an exciting partnership which brings together leading UK, European and US centres with expertise in both ocular imaging and trial endpoint design, with new applications to the complex field of uveitis. Although most uveitis specialists primarily use the OCT for detecting and measuring macular oedema, we believe that in the next few years its applications will rapidly diversify enabling us to have similar precise objective quantification of a number of key indicators of disease activity in uveitis.

 

References

  1. Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardizationof vitreal inflammatory activity in intermediate and posterior uveitis. Ophthalmology 1985;92(4):467-71.
  2. Hornbeak DM, Payal A, Pistilli M, et al . Interobserver agreement in clinical grading of vitreous haze using alternative grading scales. Ophthalmology. 2014 Aug;121(8):1643-8. doi: 10.1016/j.ophtha.2014.02.018. Epub 2014 Mar 31. PubMed PMID: 24697913.
  3. Keane PA, Karampelas M, Sim DA et al. Objective Measurement of Vitreous Inflammation Using Optical Coherence Tomography. Ophthalmology. 2014 May15. pii: S0161-6420(14)00230-9. doi: 10.1016/j.ophtha.2014.03.006. [Epub ahead of print] PubMed PMID: 24835759.
  4. Keane PA, Balasakas K, Sim DA, Aman K, Denniston AK, Aslam T for the EQUATOR study group. Automated analysis of vitreous inflammation using SD-OCT. TVST. 2015 (in press)