Purpose
To investigate near-infrared autofluorescence (IR-AF) patterns and related changes in patients with idiopathic choroidal neovascularization (CNV) treated with intravitreal bevacizumab (IVB).
Design
Retrospective observational consecutive case series.
Methods
Bevacizumab was intravitreally injected into 12 eyes of 12 patients with idiopathic CNV as the primary treatment. Color fundus photographs, optical coherence tomography (OCT), fluorescein angiography and indocyanine green angiography (ICGA), and autofluorescence imaging short-wavelength and near-infrared autofluorescence (SW-AF and IR-AF) were performed at baseline. Changes in the autofluorescence patterns were evaluated after IVB.
Results
All 12 eyes had classic CNV on fluorescein angiography at baseline. OCT showed CNV above the retinal pigment epithelium (RPE) in all eyes. After treatment, the final best-corrected visual acuity improved significantly ( P < .001) compared with baseline. IR-AF showed ring-shaped hyperautofluorescence surrounding the CNV corresponding to the dark rim on ICGA in 6 of the 12 eyes on IR-AF at baseline. During the follow-up period after IVB, all 12 eyes had ring-shaped hyperautofluorescence. The intensity of the ring-shaped autofluorescence and its contrast increased as the CNV regressed. The contrast of the ring-shaped autofluorescence partially decreased in all 3 eyes with a recurrence.
Conclusions
Ring-shaped hyperautofluorescence on IR-AF in the eyes with idiopathic CNV may indicate an involutional process of CNV enveloped by the RPE because its area corresponded to the dark rim on ICGA that reflects regression of idiopathic CNV. IR-AF can be a useful noninvasive adjunctive examination to evaluate the involution of CNV.
Submacular Choroidal Neovascularization (CNV) can develop in patients younger than 50 years in association with the presumed ocular histoplasmosis syndrome (POHS), high myopia, angioid streaks, and traumatic choroidal rupture, among others. When CNV develops in the macula with no predisposing abnormalities, it is called idiopathic CNV. Idiopathic CNV rather than POHS, a leading cause of neovascular maculopathy in young adults in Japan, appears as type 2 CNV, as proposed by Gass, and is diagnosed by findings on fluorescein angiography (FA) and optical coherence tomography (OCT). Idiopathic CNV often shows spontaneous regression. However, some studies have reported that about 20% to 30% of patients have poor visual outcomes during the natural course of the disease. Recent studies have shown that bevacizumab (Avastin; Genentech, San Francisco, California, USA) is effective for treating CNV secondary to age-related macular degeneration (AMD), pathologic myopia, angioid streaks, or POHS. Some studies also have reported that bevacizumab is effective for treating idiopathic CNV.
Although near-infrared autofluorescence (IR-AF) was reported in 1990s, the origin has been unknown. Recently several reports revealed the nature of near-infrared autofluorescence. Keilhauer and associates reported that near-infrared autofluorescence images using a confocal scanning laser ophthalmoscope (SLO) was originated from melanin in the retinal pigment epithelium (RPE) and choroid. In addition, the patterns of IR-AF in AMD and central serous chorioretinopathy (CSC) have been reported. IR-AF imaging may help us understand the pathologic changes in the RPE and choroid that develop in patients with idiopathic CNV. We evaluated the IR-AF images from eyes with idiopathic CNV that had been treated with intravitreal bevacizumab (IVB) injections as an initial treatment.
Methods
We reviewed retrospectively 12 eyes of 12 consecutive patients (4 men, 8 women) with treatment-naïve idiopathic CNV who sought care at Fukushima Medical University Hospital from April 12, 2006 to January 4, 2010. All patients were treated with IVB and followed for 6 to 41 months (mean, 21.7 months). All patients provided written informed consent before IVB. The inclusion criteria were age 50 years or younger, axial length below 26.5 mm, and previously untreated subfoveal or juxtafoveal idiopathic CNV. Patients with angioid streaks, ocular trauma, hereditary diseases, POHS, uveitis, and AMD or pregnant women were excluded. All patients underwent a standardized examination including slit-lamp biomicroscopy with a contact lens, fundus color photography, FA, indocyanine green angiography (ICGA) with a fundus camera (TRC-50 FA/ICGA/IMAGEnet H1024 system, Topcon, Tokyo, Japan) and/or a confocal SLO (Heidelberg Retina Angiograph 2 [HRA2]; Heidelberg Engineering, Heidelberg, Germany), and spectral-domain OCT (3D-OCT; Topcon, Tokyo, Japan; Spectralis-OCT, Heidelberg Engineering). FA and OCT was performed to determine the location and activity of the CNV. A clinical diagnosis of idiopathic CNV was established based on the clinical features, FA, ICGA, and OCT findings (CNV protruding through the RPE). IR-AF and short-wavelength autofluorescence (SW-AF) were performed using the HRA2. The pairs of excitation laser and detection filters were 488 and 500 nm in SW-AF and 787 and 800 nm in IR-AF. The imaging field was 30 × 30 degrees (768 × 768 pixels). AF images were obtained after maximum pupillary dilation was achieved with instillation of 0.5% tropicamide and 0.5% phenylephrine. Focusing was achieved at 815 nm, and reflectance images were taken. After switching to 787-nm excitation (indocyanine green mode), the sensitivity was increased until the vessels and the disc were recognized. Averaging images were obtained using the ART module that is equipped with an HRA2 system to gain image contrast. SW-AF images were acquired in the same manner as the IR-AF images. SW-AF images were obtained after sufficient light exposure (>40 seconds) before taking angiography, because the intensity of SW-AF changes with the light exposure.
Patients underwent a comprehensive baseline ophthalmic examination including measurement of the best-corrected visual acuity (BCVA) with a Japanese standard decimal VA chart and central retinal thickness (CRT) assessed by OCT. These tests were performed at each visit before and after the initial treatment with a 1.25-mg IVB injection. Additional IVB injections were administered when the criteria of decreased BCVA or increased CRT (more than 20%) compared with the previous visit were met. The BCVA was converted to the logarithm of the minimal angle of resolution (logMAR) to facilitate a visual comparison and statistical analysis. The BCVA values are expressed as the decimal acuity converted from logMAR in this study. Statistical analysis was performed using the paired t test to compare the baseline BCVA to that at each visit.
Results
The patient profiles and the main outcomes are shown in the Table . The patient ages at diagnosis ranged from 27 to 44 years (mean, 36.1 years). Seven eyes received 1 injection during the follow-up period; 3 eyes received 2 injections; 1 eye received 3 serial injections monthly; 1 eye received 5 serial injections monthly because of a persistent serous retinal detachment (SRD). One eye with extensive retinal atrophy surrounding the CNV (Patient 11) had poor VA at the first visit. The mean BCVA significantly ( P < .001) increased from 0.48 ± 0.24 at baseline to 1.07 ± 0.53 at the final visit. The logMAR of the BCVA improved in all eyes by more than 0.2 at the final visit compared with baseline.
| Patient No. | Age at Diagnosis (Years) | Sex | Location of CNV | BCVA | No. of IVB Injections | Recurrence of CNV | Dark Rim on ICGA | Ring-Shaped Hyper-AF on IR-AF | Ring-Shaped Hyper-AFon SW-AF At Final | Follow-up (Months) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline | Final | At Diagnosis | At Final | At Diagnosis | After IVB | At Recurrence | At Final | ||||||||
| 1 | 37 | Male | Juxtafovea | 0.4 | 0.8 | 2 | Yes | No | Yes | No | Yes | Uncleared | Yes | No | 28 |
| 2 | 33 | Male | Juxtafovea | 0.8 | 2.0 | 3 | No | No | Yes | Yes | Yes | / | Yes | Yes | 38 |
| 3 | 44 | Female | Juxtafovea | 0.7 | 1.2 | 2 | Yes | No | Yes | No | Yes | Uncleared | Yes | Yes | 41 |
| 4 | 43 | Female | Juxtafovea | 0.6 | 1.0 | 1 | No | No | Yes | No | Yes | / | Yes | Yes | 6 |
| 5 | 43 | Female | Juxtafovea | 0.4 | 0.7 | 1 | No | Yes | Yes | Yes | Yes | / | Yes | Yes | 26 |
| 6 | 27 | Male | Juxtafovea | 0.5 | 2.0 | 2 | Yes | No | Yes | No | Yes | Uncleared | No | No | 27 |
| 7 | 41 | Female | Juxtafovea | 0.5 | 0.8 | 1 | No | Yes | Yes | Yes | Yes | / | Yes | Yes | 16 |
| 8 | 35 | Female | Subfovea | 0.4 | 0.9 | 1 | No | No | Yes | No | Yes | / | Yes | Yes | 6 |
| 9 | 27 | Female | Subfovea | 0.7 | 1.2 | 1 | No | Yes | Yes | Yes | Yes | / | Yes | Yes | 12 |
| 10 | 34 | Male | Juxtafovea | 0.7 | 1.2 | 5 | No | Yes | Yes | Yes | Yes | / | Yes | Yes | 31 |
| 11 | 36 | Female | Subfovea | 0.01 | 0.05 | 1 | No | No | Yes | Yes | Yes | / | Yes | Yes | 23 |
| 12 | 33 | Female | Juxtafovea | 0.1 | 1.0 | 1 | No | No | NA | No | Yes | / | Yes | Yes | 6 |
| Mean | 36.1 | 0.48 | 1.07 | 1.8 | 21.7 | ||||||||||
| SD | 5.8 | 0.24 | 0.53 | 1.2 | 12.4 | ||||||||||
OCT showed a highly or moderately reflective mass arising from the RPE in 10 of 12 eyes at the first examination. Some lesions were covered with a layer of protruding RPE, at which tissue with moderate signal intensity attached to the undersurface of the RPE appeared in 8 of the 12 eyes on OCT ( Figure 1 ) . OCT showed cystoid macular edema in 1 eye. After the IVB injection, the CRT decreased in 10 eyes and the SRD resolved in all eyes at the final visit ( Figure 2 ) . The mean CRT decreased significantly ( P = .002) from 265.7 ± 84.3 μm at baseline to 160.5 ± 7.4 μm at the final visit.
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