CRT, Vision Loss Have Complex Relationship

A retrospective analysis of data from 6 clinical trials using injectable anti-vascular endothelial growth factor (anti-VEGF) ranibizumab (Lucentis/Genentech) has shown that the relationship between some measurements may be more complex than believed.

Although relationships between best-corrected visual acuity (BSVA) and centralized retinal thickness (CRT) measured by spectral domain optical coherence tomography (SD-OCT) exist to some degree in age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), the relationships show a wide variance and may be complicated by other disease factors.

The data showed that CRT may not be the best indicator of disease progression or visual acuity in AMD or RVO. Led by William C. Ou, MD, FACS, with Retina Consultants of Houston, collected data investigating ranibizumab and dosing regimens for AMD, DME, and RVO. The 6 studies included a total of 387 eyes from 345 patients who received ranibizumab treatment in dosages ranging from 0.3 mg to 2.0 mg/ 0.05 mL and underwent BCVA testing and SD-OCCT testing scans at baseline and 12 months.

The study data suggests that AMD, RVO, and DME each have a different relationship to CRT when it comes to visual losses or gains. Although anti-VEGF treatments such as ranibizumab have been proven effective in treating all 3 diseases, there seems to be a more complex relationship, according to Ou, “between structure and visual function” necessitating more study into that relationship, including any comorbidities and/or confounding factors for each disease.

Individual analysis and analysis pooled by disease type, with a specific focus on “change in BCVA as the dependent variable and change in CRT from baseline, baseline BCVA, baseline CRT,” and other independent demographic variables such as age, gender, and comorbidity status (ex. diabetes or hypertension) were examined.

Ou and colleagues discovered that at baseline pooled data from AMD studies showed a “significant but small negative correlation” between BCVA and CRT (r= -0.24, P= .017). Pooled data on BCVA and CRT among DME patients showed “significant medium negative correlations (r = -.042, P < .001). Data from RVO trials showed no significant correlation or relationship between BCVA and CRT (r = -0.11, P = .635).

Data also showed that changes in BCVA in relation to CRT reduction (per 100 μm) “was highest for DME patients, ranging from 2.64 to 3.50 letters. Changes in BCVA in relation to CRT in AMD patients and RVO patients was lower, (+1.18 to +1.84 letters: AMD; -1.48 to +2.70 letters: RVO). Analysis of the 12-month data revealed that AMD patients saw a negligible negative correlation between BCVA and CRT change (4= -0.04, P = 718), RVO and DME patients saw a “significant negative medium correlation” (r= -0.35, P = 0.43: RVO; r= -0.45, P < .001: DME).

Ou and colleagues remarked that there may be no true relationship between BCVA and retinal thickness in AMD, but that “given the multifactorial nature of AMD, it is not unexpected that retinal thickness appears to be an inadequate isolated predictor of visual function.”

For patients with RVO, there was only a “modest correlation” between BCVA and CRT, but Ou suggested that “the lack of a significant correlation between BCVA and CRT in the present context may be at least partly attributable to the detrimental effects of ischemia” on BCVA in RVO, a factor that cannot be “captured by CRT measurements alone.” Ou stated that in comparison to the lack of correlative data on AMD and RVO, there appears to be highly significant correlations between BCVA and CRT for patients with DME.

This data suggests that assessment of retinal disease progression should factor in the relationships each of these retinal diseases has with BCVA and CRT, and avoid assumptions of commonalities among the 3 diseases. CRT, Ou suggests, may “account for only a modest portion of variability in VA among” the 3 diseases, other factors such as atrophy and ischemia may play a greater role in AMD and RVO.

The study appeared in the American Journal of Ophthalmology.