Purpose
To evaluate the therapeutic effect of intravitreal bevacizumab injection for symptomatic retinal arterial macroaneurysm.
Design
Retrospective interventional case series.
Methods
The study included 23 patients (23 eyes) with symptomatic retinal arterial macroaneurysm. They were categorized according to treatment method into 2 groups: an intravitreal bevacizumab–treated group (11 eyes) and an untreated group (12 eyes). Bevacizumab was injected at the initial visit, followed by as-needed monthly reinjection. Best-corrected visual acuity (BCVA) and central macular thickness were documented and analyzed between groups.
Results
The mean follow-up period for all subjects was 10.83 ± 4.6 months. The mean number of injections for the treated group was 1.42 ± 0.69. The mean logarithm of the minimal angle of resolution (logMAR) of BCVA improved from baseline at the last follow-up by 0.26 in the bevacizumab-treated group ( P = .02) and by 0.34 in the untreated group ( P = .005). Average central macular thickness decreased from 384.4 ± 150.1 μm to 265 ± 112.5 μm in the bevacizumab-treated group ( P = .0002) and from 413.2 ± 155.2 μm to 236.3 ± 103.5 μm in the untreated group ( P = .008). The BCVA was significantly improved from baseline after 1 month in the bevacizumab-treated group ( P = .02) and after 3 months in the untreated group ( P = .01). However, there was no statistically significant difference in BCVA improvement or central macular thickness improvement achieved at the final visit.
Conclusions
Intravitreal bevacizumab injection likely hastens resolution of macular edema and hemorrhage secondary to retinal arterial macroaneurysm. Intravitreal bevacizumab injection could be an effective treatment option for symptomatic retinal arterial macroaneurysm.
Retinal arterial macroaneurysm is an acquired large arteriolar dilation that usually occurs within the first 3 orders of the retinal arterial vasculature bifurcations, typically in the macular or postequatorial regions. Retinal arterial macroaneurysms most commonly develop in hypertensive women aged between 50 and 80. This condition may lead to visual loss secondary to macular edema or hemorrhage in 1 or all retinal layers.
The treatment of retinal arterial macroaneurysm with macular edema or hemorrhage is controversial. Some authors have reported a good visual outcome simply with observation. Even though there is no consensus about the management of retinal arterial macroaneurysm, treatment is advised in cases of exudative manifestations involving the fovea with visual acuity deterioration.
Therapeutic interventions for eyes with retinal arterial macroaneurysm include direct photocoagulation to the aneurysm itself, pneumatic displacement with tissue plasminogen activator for submacular hemorrhage secondary to retinal arterial macroaneurysm, surgical removal of associated hemorrhage with pars plana vitrectomy, and photodisruption of the internal limiting membrane (ILM) or the posterior hyaloid using neodymium:yttrium-aluminum-garnet (Nd:YAG) or argon laser to release the hemorrhage.
Recently, intravitreal injections of anti–vascular endothelial growth factor (VEGF) drugs have been considered as a treatment option for retinal arterial macroaneurysm. Several case reports have shown encouraging results of intravitreal anti-VEGF agents for retinal macroaneurysms. However, there have not been sufficient reports about anti-VEGF treatment for retinal arterial macroaneurysm. We hypothesized that intravitreal bevacizumab administration may be effective in treating retinal arterial macroaneurysm with macular edema and/or hemorrhage. The purpose of the current study was to evaluate the efficacy of intravitreal bevacizumab in treating eyes with retinal arterial macroaneurysm.
Methods
We retrospectively reviewed the medical records of 58 consecutive patients with retinal arterial macroaneurysm who were treated at the Retina Center of Kim’s Eye Hospital in Konyang University College of Medicine from June 2008 through February 2012. This study was approved by the Institutional Review Board of Kim’s Eye Hospital, Konyang University College of Medicine. Clinical research in this study followed the tenets of the Declaration of Helsinki.
Inclusion and Exclusion Criteria
Records for patients who met the following criteria were included in this study: (1) diagnosis of symptomatic retinal arterial macroaneurysm (defined as retinal arterial macroaneurysm with exudative foveal manifestations [including subretinal/intraretinal fluid, hard exudates, and/or hemorrhages]); (2) vision loss attributable to macular exudates or hemorrhage; (3) retinal arterial macroaneurysm confirmed by fluorescein angiography (FA) and indocyanine green angiography (ICGA), performed using a confocal laser scanning system (HRA-2; Heidelberg Engineering, Dossenheim, Germany) at the first visit; (4) treatment naiveté; and (5) a minimum follow-up period of 6 months. No limits on visual acuity were set for either inclusion or exclusion criteria.
Exclusion criteria included the following: (1) no edema or hemorrhage involving the macula despite definite retinal arterial macroaneurysm; (2) any other treatment except intravitreal bevacizumab injection; (3) cases complicated by thick vitreous hemorrhage requiring vitrectomy; (4) other ocular diseases that could affect visual acuity; and (5) previous vitreoretinal surgery.
Patients were divided into 2 groups according to the treatment method: (1) the bevacizumab-treated group, in which intravitreal bevacizumab injection was performed; and (2) the untreated group, in which patients were observed but not treated.
Outcome Measures
The primary outcome was the mean change from baseline in best-corrected visual acuity (BCVA) at 1, 3, and 6 months and at the final visit. The secondary outcome was the mean change from baseline for central macular thickness (as measured by spectral-domain optical coherence tomography [SD-OCT, Spectral OCT/SLO; OTI Ophthalmic Technologies Inc, Miami, Florida, USA]) at 1, 3, and 6 months and at the final visit. The percentage of patients gaining or losing more than 3 lines of vision, as measured from baseline, was also examined.
BCVA was assessed using the Snellen chart at baseline and at each monthly follow-up visit after intravitreal bevacizumab injection treatment. For statistical analysis, the Snellen BCVA was converted to logarithm of the minimal angle of resolution (logMAR) values.
Central macular thickness was assessed by measurement of retinal thickness of the 1-mm central retina, which was obtained by a macular scan. Only well-centered scans without overt algorithm failure messages were selected for analysis.
Intravitreal Bevacizumab Injection Treatment
The off-label nature of the treatment and its potential risks and benefits were discussed in detail with patients. Informed consent was obtained from all patients before intravitreal injection of bevacizumab. Patients were chosen for intravitreal bevacizumab injection if they declined other treatment methods such as laser photocoagulation or vitrectomy. Cases were also included if it was not possible to perform direct laser photocoagulation to the aneurysm because of thick preretinal hemorrhage or if patients were unable to keep the required face-down position after expansive gas injection for submacular hemorrhage. Intravitreal bevacizumab (1.25 mg/0.05 mL; Avastin; Genentech Inc, South San Francisco, California, USA) injections were performed for all patients with the same treatment and retreatment protocols. After the first injection, patients were retreated if any of the following were observed: (1) evidence of persistent fluid or hemorrhage involving the macula on OCT at least 1 month after the previous injection; (2) visual deterioration of more than 2 lines; or (3) evidence of an active retinal arterial macroaneurysm lesion, as found on fundus examination, FA, ICGA, or OCT.
Statistical Analysis
SPSS software version 13.0 (SPSS Inc, Chicago, Illinois, USA) was used for all analyses. Frequencies were compared between treatment groups using Fisher exact test. Comparative statistics were determined using unpaired 2-sided t tests. For the nonparametric data, the Mann-Whitney U test and the Kruskal-Wallis test were used. A P value of less than .05 was considered statistically significant.
Results
Out of the 58 patient records examined, 23 eyes (23 patients) were included in analysis and 35 eyes (35 patients) were excluded from analysis. Eleven eyes had no macular hemorrhage or exudates, 12 required vitrectomy because of a thick vitreous hemorrhage, and 12 were treated using laser photocoagulation or a combination of intravitreal anti-VEGF and laser photocoagulation. Table 1 summarizes patient characteristics and their treatment results. The mean age of the subjects was 70.3 ± 9.5 years (range, 59-83 years). The mean BCVA of all the subjects at baseline was 0.85 ± 0.32 logMAR units and the mean central macular thickness at baseline was 398.8 ± 144.2. The mean follow-up period was 10.83 ± 4.6 months (range, 6-23 months).
| Patient | Age/Sex | Complication Type | Duration of Symptoms (d) | Foveal Condition at Presentation | Treatment | Initial BCVA | Final BCVA | Initial CMT (μm) | Final CMT (μm) | Follow-up Period (mo) |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 77/F | Hemorrhagic | 14 | SRD, intraretinal edema | IVB #1 | 20/50 | 20/25 | 437 | 252 | 23 |
| 2 | 73/F | Hemorrhagic | 4 | Sub-ILM hemorrhage, preretinal hemorrhage | IVB #1 | 10/200 | 20/100 | 411 | 207 | 10 |
| 3 | 81/F | Hemorrhagic | 15 | SRD, intraretinal edema | IVB #1 | 10/200 | 20/50 | 661 | 302 | 10 |
| 4 | 62/F | Hemorrhagic | 10 | SRD, intraretinal edema | None | 20/30 | 20/30 | 256 | 197 | 12 |
| 5 | 73/F | Hemorrhagic | 14 | SRD | None | 20/30 | 20/25 | 247 | 212 | 18 |
| 6 | 64/F | Hemorrhagic | 1 | Sub-ILM hemorrhage, preretinal hemorrhage | None | 10/200 | 20/100 | 482 | 286 | 8 |
| 7 | 63/M | Exudative | 30 | SRD | IVB #1 | 20/100 | 20/25 | 284 | 184 | 8 |
| 8 | 70/F | Exudative | 20 | Intraretinal edema | None | 20/70 | 20/40 | 256 | 221 | 20 |
| 9 | 73/F | Exudative | 28 | SRD | IVB #1 | 20/70 | 20/40 | 448 | 273 | 12 |
| 10 | 82/F | Hemorrhagic | 21 | SMH | None | 20/200 | 10/200 | 321 | 225 | 6 |
| 11 | 76/F | Hemorrhagic | 2 | Sub-ILM hemorrhage, preretinal hemorrhage | None | HM | 20/25 | 586 | 311 | 10 |
| 12 | 59/F | Hemorrhagic | 3 | SMH | IVB #3 | 20/70 | CF | 642 | 146 | 7 |
| 13 | 60/F | Exudative | 2 | SRD, intraretinal edema | IVB #2 | 20/25 | 20/20 | 445 | 176 | 17 |
| 14 | 74/F | Hemorrhagic | 7 | SMH, preretinal hemorrhage | None | CF | 10/200 | 288 | 224 | 9 |
| 15 | 75/M | Hemorrhagic | 2 | Sub-ILM hemorrhage, preretinal hemorrhage | None | CF | 20/100 | 467 | 237 | 7 |
| 16 | 64/F | Hemorrhagic | 2 | Sub-IL M hemorrhage, preretinal hemorrhage | None | CF | 20/30 | 334 | 205 | 6 |
| 17 | 78/M | Hemorrhagic | 5 | Sub-ILM hemorrhage, preretinal hemorrhage | IVB #2 | CF | 20/50 | 552 | 206 | 9 |
| 18 | 83/F | Exudative | 3 | Intraretinal edema | None | CF | 20/40 | 356 | 188 | 7 |
| 19 | 68/F | Hemorrhagic | 1 | SMH, sub-ILM hemorrhage | IVB #1 | 20/100 | 20/40 | 552 | 221 | 10 |
| 20 | 62/M | Hemorrhagic | 4 | SRD | IVB #2 | 20/50 | 20/30 | 256 | 195 | 6 |
| 21 | 79/F | Hemorrhagic | 2 | Sub-ILM hemorrhage, preretinal hemorrhage | None | CF | 20/200 | 412 | 224 | 10 |
| 22 | 72/F | Hemorrhagic | 10 | Sub-ILM hemorrhage, preretinal hemorrhage | None | 5/200 | 20/50 | 399 | 212 | 13 |
| 23 | 64/F | Exudative | 1 | SRD, intraretinal edema | IVB #1 | 5/200 | 20/50 | 446 | 233 | 11 |
The bevacizumab-treated group contained 11 eyes of 11 patients, and the untreated group contained 12 eyes of 12 patients. Both groups had similar baseline characteristics for age, sex, duration of symptoms, baseline BCVA, baseline central macular thickness, and complication type ( Table 2 ).
| Bevacizumab-Treated Group (11 Eyes of 11 Patients) | Untreated Group (12 Eyes of 12 Patients) | P | |
|---|---|---|---|
| Age (y) | 62.6 ± 10.42 | 72.8 ± 6.88 | .24 a |
| Sex | |||
| Male | 2 (18.2%) | 2 (16.7%) | |
| Female | 9 (81.8%) | 10 (83.3%) | .73 b |
| Duration of symptoms (d ± SD) | 10.3 ± 9.5 | 8.7 ± 7.5 | .53 a |
| Baseline BCVA (logMAR) | 0.76 ± 0.38 | 0.93 ± 0.42 | .28 a |
| Baseline CMT ± SD (μm) | 384.4 ± 150.1 | 413.2 ± 155.2 | .22 a |
| Complication type | |||
| Hemorrhagic | 7 (63.6%) | 9 (75.0%) | |
| Exudative | 4 (36.4%) | 3 (25.0%) | .66 b |
At baseline, the mean logMAR of BCVA in the bevacizumab-treated group and the untreated group was 0.76 ± 0.38 (Snellen equivalent: 20/115) and 0.93 ± 0.42 (Snellen equivalent: 20/170), respectively. With follow-up, the mean logMAR BCVA significantly decreased over time in both groups ( Figure 1 ). At the final visit, the mean logMAR BCVA in both groups had significantly decreased to 0.50 ± 0.32 (Snellen equivalent: 20/63) ( P = .002) and 0.59 ± 0.38 (Snellen equivalent: 20/77) ( P = .0005), respectively.
The mean central macular thickness at baseline in the bevacizumab-treated group and untreated group was 384.4 ± 150.1 μm and 413.2 ± 155.2 μm, respectively. With follow-up, the mean central macular thickness significantly decreased over time in both groups ( Figure 2 ). At the final visit, the central macular thickness of both the bevacizumab-treated group and the untreated group had significantly decreased to 265.6 ± 112.5 μm ( P = .0002) and 236.3 ± 103.5 μm ( P = .008), respectively. Both groups showed improvement in central macular thickness from baseline with follow-up.
