Assessment of differential pharmacodynamic effects using optical coherence tomography in neovascular age-related macular degeneration

Abstract

Purpose: To use novel OCT parameters in assessing the differential pharmacodynamic effects of bevacizumab (Avastin; Genentech, South San Francisco, CA), pegaptanib (Macugen; OSI Pharmaceuticals, New York, NY), and verteporfin photodynamic therapy (PDT; Novartis, Basel, Switzerland) in a recently completed phase III/IV clinical trial.

Methods: Data from 122 patients participating in the Avastin (Bevacizumab) for Choroidal Neovascularization (ABC) trial, were evaluated. OCT scans were analyzed with custom software. Changes in the volume of the neurosensory retina, amount of subretinal fluid (SRF), pigment epithelium detachment (PED), and subretinal tissue (SRT), were calculated over the 54-week trial period.

Results: Reductions in retinal edema were more than twice as great from bevacizumab as from pegaptanib (-0.82 mm³ vs. -0.31 mm³), whereas SRF reduction was more than three times greater (-0.54 mm³ vs. -0.15 mm³. Both bevacizumab and pegaptanib led to rapid reductions in SRT; however, in those receiving pegaptanib, these improvements were not maintained (at week 54, -0.22 mm³ vs. +0.18 mm³). Acute increases in SRF were seen 1 week after PDT (+0.36 mm³) and, across all treatment groups, PED volume tended to remain unchanged or to regress only slowly.

Conclusions: In clinical trials, quantitative OCT subanalysis increases the amount of clinically useful information that can be obtained from OCT images. In the emerging era of neovascular AMD therapeutics, the capacity of OCT to provide such detailed pharmacodynamic information in a noninvasive manner is likely to attain increased importance. In future comparative studies, evaluation of SRT may highlight differential effects on vascular proliferation, whereas measurement of PED volume may be useful for the estimation of retinal and subretinal pigment epithelium (RPE) therapeutic penetration. (ClinicalTrials.gov number, ISRCTN83325075.).

Figure 1.

(A, C) Optical coherence tomography (OCT) B-scans of eyes demonstrating SRF, SRT, and FVPED. (B, D) The clinically relevant boundaries are graded using OCTOR (computer-assisted manual grading) software, which then computes the volumes of the spaces (retina, SRF, SRT, and FVPED) defined by these boundaries.

Figure 2.

(A) Mean change from baseline in total volume of the neurosensory retina in those receiving bevacizumab versus those receiving standard therapy (photodynamic therapy with verteporfin, or pegaptanib). (B) Mean change from baseline in total volume of SRF in those receiving bevacizumab versus those receiving standard therapy (photodynamic therapy with verteporfin or pegaptanib).

Figure 3.

(A) Mean change from baseline in total volume of SRT in those receiving bevacizumab versus those receiving standard therapy (PDT with verteporfin or pegaptanib). (B) Mean change from baseline in total volume of PED in those receiving bevacizumab versus those receiving standard therapy (photodynamic therapy with verteporfin or pegaptanib).

Figure 4.

(A) Mean change from baseline in total volume of the neurosensory retina in those receiving bevacizumab (Avastin; Genentech) versus those receiving PDT with verteporfin (Novartis) for classic (PC) or classic (C) lesions. (B) Mean change from baseline in total volume of the neurosensory retina in those receiving bevacizumab versus those receiving pegaptanib (Macugen; OSI Pharmaceuticals) for minimally classic (MC) or occult (O) lesions. (C) Mean change from baseline in total volume of SRF in those receiving bevacizumab versus those receiving PDT with verteporfin (PC/C lesions). (D) Mean change from baseline in total volume of SRF in those receiving bevacizumab versus those receiving pegaptanib (MC/O lesions).

Figure 5.

(A) Mean change from baseline in total volume of SRT in those receiving bevacizumab (Avastin; Genentech) versus those receiving photodynamic therapy (PDT) with verteporfin for predominantly classic (PC) or classic (C) lesions. (B) Mean change from baseline in total volume of SRT in those receiving bevacizumab versus those receiving pegaptanib (Macugen; OSI Pharmaceuticals) for minimally classic (MC) or occult (O) lesions. (C) Mean change from baseline in total volume of PED in those receiving bevacizumab versus those receiving PDT with verteporfin for PC/C lesions. (D) Mean change from baseline in total volume of PED in those receiving bevacizumab versus those receiving pegaptanib for MC/O lesions.