SEARCH

SEARCH BY CITATION

Keywords:

  • intravitreal bevacizumab;
  • Avastin;
  • exudative age-related macular degeneration;
  • intraocular antiangiogenesis

Abstract.

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

Purpose:  To examine an association between the subfoveal neovascular membrane type and visual acuity change after intravitreal bevacizumab injection for exudative age-related macular degeneration (AMD).

Methods:  We carried out a clinical, retrospective, interventional case-series study including 66 consecutive patients (67 eyes) with exudative AMD who received an intravitreal injection of 1.5 mg bevacizumab. Study subgroups included the occult type without or with minimally classic subfoveal neovascularization (n = 28 eyes, 42%), predominantly or purely classic subfoveal neovascularization (n = 22 eyes, 33%), and eyes with retinal pigment epithelium detachment (n = 17 eyes, 25%). Follow-up was ≥ 2 months.

Results:  The maximal visual acuity (VA) gain (mean ± standard deviation − 0.07 ± 0.30 logMAR, 0.5 ± 2.9 Snellen lines; p = 0.87), and VA gain at 1 month (p = 0.10), 2 months (p = 0.77) and 3 months (p = 0.35) after the injection did not vary significantly between the three study subgroups. Correspondingly, a multivariate analysis did not reveal a statistically significant (p = 0.57) influence of subfoveal lesion type on gain in VA.

Conclusions:  Visual improvement after intravitreal bevacizumab does not differ markedly between various types of subfoveal neovascularization in AMD.


Introduction

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

The emergence of a new paradigm which considers the vitreous cavity as a drug reservoir has led to a profound change in the treatment of exudative age-related macular degeneration (AMD), whereby antiangiogenic substances are injected into the vitreous cavity. The first substance to be used on a large scale was triamcinolone acetonide, followed by the non-steroidal drugs pegaptanib, ranibizumab and bevacizumab (Spaide et al. 2003;Penfold et al. 1995; Gragoudas et al. 2004; Rosenfeld et al. 2005; Augustin & Schmidt-Erfuhrt 2006; Avery et al. 2006; Heier et al. 2006; Spaide et al. 2006). Since the first report by Rosenfeld et al. (2005), intravitreal bevacizumab has been applied to exponentially increasing numbers of eyes for the treatment of AMD (Avery et al. 2006; Spaide et al. 2006). However, so far it has remained unclear whether the effect of intravitreal bevacizumab on visual function depends on the type of subfoveal membrane. It was therefore the purpose of the present study to examine whether the type of subfoveal neovascular membrane influences the change in visual acuity (VA) after intravitreal injection of bevacizumab as treatment for exudative AMD.

Materials and Methods

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

This clinical interventional case-series study included 66 consecutive patients (67 eyes) with exudative AMD who received an intravitreal injection of 1.5 mg bevacizumab. The subjects' mean age was 78 ± 8 years (range 51–97 years). The patients were fully informed of the experimental character of the treatment and signed informed consent. According to the appearance of the subfoveal neovascular membrane in fluorescein angiograms, the whole study group was divided into occult type without or with minimally classic subfoveal neovascularization (with a < 50% classic component; n = 28 eyes, 42%), predominantly or purely classic type (with a > 50% classic component; n = 22 eyes, 33%), and eyes with detachment of the retinal pigment epithelium (n = 17 eyes, 25%). Follow-up periods were ≥ 2 months. The injections were carried out in the operating theatre under the same conditions as any other intraocular intervention. The patients received 1.5 mg bevacizumab. During the follow-up, no additional ocular surgery including cataract surgery was carried out. At baseline, all patients underwent an ophthalmological examination including refractometry and measurement of VA, applanation tonometry and fluorescence angiography. Study patients were then re-examined at approximately monthly intervals. Visual acuity was determined in a standardized fashion by unmasked observers performing best corrected refractometry. Statistical analyses were performed using spss for Windows, Version 13.0 (SPSS, Chicago, IL, USA).

Results

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

The maximal gain in VA (mean ± standard deviation [SD]− 0.07 ± 0.30 logMAR [0.5 ± 2.9 Snellen lines]; p = 0.87; analysis of variance) and the gain in VA at 1 month (− 0.08 ± 0.22 logMAR [0.8 ± 2.2 Snellen lines]; p = 0.10), 2 months (− 0.07 ± 0.24 logMAR [0.8 ± 2.4 Snellen lines]; p = 0.77) and 3 months (− 0.02 ± 0.29 logMAR [0.4 ± 2.7 Snellen lines]; p = 0.35) after the injection did not vary significantly between the three study subgroups (Fig. 1). Correspondingly, a multivariate analysis with age, type of subfoveal lesion and baseline VA as independent variables and maximal VA gain as a dependent variable revealed that age (p = 0.42; 95% confidence interval [CI]− 0.13 to 0.06), baseline VA (p = 0.78; 95% CI − 0.23 to 0.17) and type of subfoveal membrane (p = 0.57; 95% CI − 0.68 to 1.23) were not statistically significantly associated. Similar results for the association between type of subfoveal neovascular membrane and VA were obtained in examinations at 1 month after the injection (p = 0.32; 95% CI − 0.60 to 1.78), 2 months after the injection (p = 0.27, 95% CI − 0.55 to 1.86), and 3 months after the injection (p = 0.19, 95% CI − 0.55 to 2.59).

image

Figure 1.  Boxplots showing the distribution of the maximal gain in visual acuity during follow-up of ≥ 2 months after intravitreal injection of 1.5 mg bevacizumab for treatment of exudative age-related macular degeneration in 67 eyes. The difference in gain between patients with the occult or minimally classic type of subfoveal neovascular membrane (n = 28), patients with the predominantly or purely classic type of subfoveal neovascular membrane (n = 22), and patients with retinal pigment epithelium detachment (n = 17) was not statistically significant (p = 0.87).

Download figure to PowerPoint

Discussion

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

Since the year 2000, intravitreal injections, namely intraocular triamcinolone acetonide applications, have been used increasingly for the treatment of intraocular oedematous and neovascular diseases, such as central and branch retinal vein occlusion, diffuse diabetic macular oedema, proliferative diabetic retinopathy, neovascular glaucoma without or with cataract surgery, proliferative vitreoretinopathy, chronic prephthisical ocular hypotony, chronic uveitis, persistent pseudophakic cystoid macular oedema, and exudative AMD, particularly if combined with photodynamic therapy (Wingate & Beaumont 1999; Danis et al. 2000; Jonas et al. 2002; Jonas 2005). In recent months, however, intravitreal triamcinolone acetonide has been largely replaced by intravitreal bevacizumab for therapy of exudative AMD (Rosenfeld et al. 2005; Avery et al. 2006; Spaide et al. 2006). Correspondingly, a recent study showed a significantly better visual outcome after intravitreal bevacizumab than after intravitreal triamcinolone for exudative AMD (Jonas JB, unpublished data). As exudative AMD can be divided into several subtypes, it was the purpose of the present study to assess whether visual outcomes after intravitreal bevacizumab differ between these subtypes.

The results of the study suggest that VA gain after intravitreal bevacizumab does not markedly differ between the various types of subfoveal neovascularization in AMD. These results run parallel to those of previous studies on the intravitreal use of pegabtanib and ranibizumab, in which the change in VA after the injection was found to be mostly independent of the type of subfoveal neovascular membrane (Gragoudas et al. 2004; Heier et al. 2006). Given that the improvement in VA was similar in classic subfoveal neovascularization to that in other subgroups, future studies might address whether intravitreal bevacizumab should be used as a first-line treatment for classic subfoveal membrane in AMD.

There are limitations to the present study. The most important concerns its design as a case-series study without a control group. However, as it was not the purpose of the investigation to assess the efficacy of the treatment but to compare the clinical outcome between patients with various types of the disease, a randomized controlled study design might not have added markedly more information on the issue in question. The relatively small number of patients included in the study represents another limiting factor: further investigations may have to be awaited for additional data on the topic.

In conclusion, the data from the present comparative study suggest that bevacizumab at a dosage of 1.5 mg leads to an increase in VA within the first 2 months after an intravitreal injection, independently of the type of subfoveal neovascularization. More recent data on the safety and full-thickness retinal penetration of bevacizumab (Maturi et al. 2006; Shahar et al. 2006) and on the experimental and clinical use of bevacizumab (Bashshur et al. 2006; Luke et al. 2006; Rich et al. 2006; Spaide et al. 2006; Spitzer et al. 2006) may imply that the data presented in the present study point towards the application of intravitreal bevacizumab in the treatment of all types of exudative age-related macular degeneration.

References

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References