Functional outcomes after multiple treatments with ranibizumab in neovascular age-related macular degeneration beyond visual acuity

Abstract

Purpose: To evaluate neuroretinal function and anatomical outcomes in patients with neovascular age-related macular degeneration (AMD) after three treatments with ranibizumab.

Design: Observational case reports.

Methods: We investigated visual function in three patients, one female (80 years) and two male (77 and 74 years) with neovascular AMD. Twenty healthy participants served as control group. We measured visual acuity (Bailey-Lovie charts), contrast sensitivity (Pelli-Robson) and neuroretinal function using the multifocal electroretinogram (mfERG). Central macular thickness was evaluated using optical coherence tomography (OCT). Main outcome measures were central and peripheral mfERG peak to trough (N1P1) response density amplitudes and peak (P1) implicit times. All tests were performed before the first treatment (baseline) and after each of the three treatments with intravitreal 0.3 mg ranibizumab.

Results: Visual acuity and contrast sensitivity remained stable or improved. Central macular thickness decreased after three treatments in all three patients. We found no significant change in central and peripheral neuroretinal function in the AMD patients between pre- and post-treatments 2 and 3. Although the mfERG amplitudes in the AMD patients were not significantly reduced compared with the age-similar group at baseline, there was a statistically significant reduction in central and peripheral mfERG amplitudes after three treatments

Conclusion: Anatomical outcomes and central visual function improved or remained stable in the three AMD patients in concordance with past reports. Further investigations of possible adverse effects of ranibizumab on the central and peripheral neuroretina in large prospective clinical trials are suggested.

Keywords: OCT; age-related macular degeneration; multifocal ERG; multifocal electroretinogram; optical coherence tomography; ranibizumab.

Figure 1

The mfERG uses black and white hexagons presented on a monitor (left) that flicker according to a pseudorandom m-sequence. Each waveform represents the electrical response from a hexagon which stimulates a focal retinal area. The waveforms can be plotted as a trace array (middle) or as a three dimensional response density (amplitudes per unit retinal area) plot (right). The latter reflects the distribution of the cone-mediated (photoreceptor and bipolar) cellular responses.

Figure 2

The stimulus array (right) and how the waveform responses were averaged into a central (1) and peripheral (2) area are shown. We analyzed N1P1 trough to peak amplitude response densities and P1 peak implicit times (arrows).

Figure 3

The N1P1 amplitudes ± SD (A) and peak implicit times ± SD (B) for the central and peripheral rings for each ARM patient are shown compared with a healthy control group. While P1 implicit times remained stable, N1P1 amplitudes were significantly reduced after the third treatment.

Figure 4

The mfERG and OCT results for the AMD 1 (A), AMD 2 (B) and AMD 3 (C) are demonstrated. The mfERG central and peripheral area waveform averages (a) and OCT images (b) before and after three treatments are shown for each patient. In c. the three dimensional response density plots of each patient compared with the age-similar control group (n = 20) are outlined before and after three treatments with ranibizumab. Note that darker gray scales indicate poorer response densities which were evident in all patients after the third treatment. These were not only reduced in the central area but throughout the whole field up to 25° (see also waveform averages in a).