Purpose
To test whether oxygen saturation is affected in retinal blood vessels in patients with central retinal vein occlusion (CRVO).
Design
Prospective observational case series.
Methods
Oxygen saturation of hemoglobin was measured in retinal blood vessels in 10 patients with unilateral CRVO. The duration of CRVO before measurement was from 1 day to about 6 months. Two patients were excluded because of poor quality of oximetry images. The spectrophotometric retinal oximeter is based on a fundus camera. It simultaneously captures images of the retina at 605 nm and 586 nm and calculates optical density (absorbance) of retinal vessels at both wavelengths. The ratio of the 2 optical densities is approximately linearly related to hemoglobin oxygen saturation. Mean oxygen saturation was calculated for first- and second-degree arterioles and venules in both eyes of each patient.
Results
The mean oxygen saturation of hemoglobin in retinal venules was 49% ± 12% (mean ± SD, n = 8) in eyes affected by CRVO and 65% ± 6% in unaffected fellow eyes ( P = .003). The mean arteriolar oxygen saturation was 99% ± 3% in CRVO eyes and 99% ± 6% in the fellow eyes. Venular oxygen saturation was variable within and between CRVO eyes.
Conclusions
Oxygen saturation in retinal venules is lower in eyes with CRVO than in fellow eyes and there is considerable variability within and between CRVO eyes. Arteriolar saturation is the same in CRVO and fellow eyes. Retinal oxygenation is disturbed in CRVO.
Central retinal vein occlusion (CRVO) disturbs retinal blood circulation and is associated with a variable degree of capillary nonperfusion on fluorescein angiography. CRVO can therefore be expected to cause hypoxia in the inner retina. Two studies have suggested disturbed retinal oxygenation in CRVO. Yoneya and associates studied oxygenation of the retina with an imaging device. They reported a semi-quantitative association between decreased tissue oxygen saturation and fluorescein angiography findings in patients with ischemic CRVO. Williamson and associates recently measured partial pressure of oxygen (PO 2 ) with intravitreal oxygen probes during vitrectomy. They found lower preretinal PO 2 in patients with CRVO, when compared with patients undergoing vitrectomy for either a macular hole or epiretinal membrane removal.
Retinal hypoxia may play a key role in CRVO. On one hand, it may be a reliable measure of the severity of the occlusion. On the other hand, hypoxic induction of cytokines, such as vascular endothelial growth factor, may be central in the consequences of CRVO, such as retinal edema and iris neovascularization.
In the current study we use a novel noninvasive retinal oximeter to measure oxygen saturation in retinal vessels in patients with CRVO.
Methods
Patients
The study was a prospective observational case series. Oxygen saturation measurements were made in 10 consecutive patients with unilateral CRVO before any treatment, except for successful treatment of acute glaucoma in 1 patient. Data from 2 patients were excluded because of poor quality of oximetry images. The age of the included patients was 61 ± 12 years (mean ± SD, n = 8). One patient was amblyopic on the affected eye and 1 was amblyopic on the fellow eye.
Retinal Oximetry
The retinal oximeter (Oxymap ehf, Reykjavik, Iceland) has been described previously. It is based on a fundus camera (Canon CR6-45NM; Canon Inc, Tokyo, Japan), which is coupled with a beam splitter (MultiSpec Patho-Imager; Optical Insights, Tucson, Arizona, USA) and a digital camera (SBIG ST-7E; Santa Barbara Instrument Group, Santa Barbara, California, USA). It yields fundus images with 4 wavelengths of light simultaneously. Specialized software automatically selects measurement points on the oximetry images and calculates the optical density (absorbance) of retinal vessels at 2 wavelengths, 605 nm and 586 nm. Optical density is sensitive to oxygen saturation at 605 nm but not at the reference wavelength, 586 nm. The ratio of these optical densities is approximately linearly related to hemoglobin oxygen saturation and the oximeter yields relative oxygen saturation values.
Infrared light was used to align the fundus camera (oximeter) and the images were taken in a dark room. The time between images (flashes) of the same eye was on average about 1 minute. Pupils were dilated with 1% tropicamide (Mydriacyl, S.A. Alcon-Couvreur N.V., Puurs, Belgium), which was in some cases supplemented with 10% phenylephrine hydrochloride (AK-Dilate; Akorn Inc, Lake Forest, Illinois, USA). The fellow eye was not dilated in 3 cases (adequate dilation of pupil in darkness).
Oxygen saturation was measured in first- and second-degree retinal arterioles and venules in both eyes. Mean oxygen saturation in arterioles and mean saturation in venules was calculated for each eye. Each mean saturation value is constructed from the same ratio of temporal/nasal vessels as the mean in the other eye in the same patient. In order to achieve this matching, in some cases, 2 vessel segments (temporal or nasal) were averaged and entered as 1 for calculation of the mean for the eye.
The oximeter estimates light absorbance by measuring light intensity outside and inside retinal vessels. Extravascular hemorrhages may therefore interfere with measurements. Care was taken to avoid measuring vessel segments with adjacent hemorrhages to reduce possible artifacts.
Statistical analysis was performed with Prism, version 5 (GraphPad Software Inc, LaJolla, California, USA) and paired t tests were used for comparisons of means.
Results
The Table and Figure 1 show decreased venular oxygen saturation, 49% ± 12%, in eyes with CRVO when compared with healthy fellow eyes, 65% ± 6%, in the same patients (mean ± SD, n = 8, P = .003, paired t test). The Table shows mean and standard deviation of oxygen saturation measurements in several vessels in each eye of patients with CRVO. The standard deviations reflect the degree of topographic variability within each eye.
| Patient No. | Affected Eye a | Fellow Eye a | Duration of Occlusion | ||
|---|---|---|---|---|---|
| Arterioles | Venules | Arterioles | Venules | ||
| 1 | 95 ± 4 (2) | 53 ± 2 (3) | 94 ± 3 (2) | 59 ± 1 (3) | 1 day. Fellow eye amblyopic. |
| 2 | 99 ± 4 (4) | 50 ± 12 (4) | 96 ± 3 (3) | 62 ± 7 (3) | 1–2 days. |
| 3 | 101 ± 1 (2) | 30 ± 25 (5) | 103 ± 10 (2) | 67 ± 11 (4) | 2 days. |
| 4 | 101 (1) | 54 ± 17 (3) | 92 (1) | 68 ± 3 (3) | About 1 month. |
| 5 | 96 ± 0.5 (3) | 39 ± 10 (5) | 96 ± 0.6 (3) | 60 ± 9 (5) | About 3 months. |
| 6 | 100 ± 5 (2) | 72 ± 7 (5) | 98 ± 3 (2) | 76 ± 5 (5) | About 3 months. |
| 7 | 102 ± 2 (2) | 50 ± 10 (6) | 108 ± 2 (2) | 64 ± 7 (4) | About 3 months. Acute glaucoma treated 2 months earlier. |
| 8 | 103 (1) | 47 ± 13 (4) | 105 (1) | 66 ± 4 (4) | About 6 months. Affected eye amblyopic. |
| Patients 1–8 (Mean ± SD) | 99 ± 3 | 49 ± 12% b | 99 ± 6 | 65 ± 6 b | |
a Mean ± SD (number of measured vessels in each eye in parentheses).
b Affected venules have significantly lower saturation than venules in fellow eye, P = .003.
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