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From the Indiana University School of Medicine, Indianapolis.
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Abstract |
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METHODS. Eleven subjects with occult subfoveal CNVM due to AMD were assessed in a masked fashion by color Doppler imaging (CDI) within 24 hours before, 24 hours after, and 1 month after undergoing TTT.
RESULTS. In the posterior ciliary arteries (PCAs), there were no statistically significant changes observed in the peak systolic velocity (PSV), end diastolic velocity (EDV), or resistive index (RI) at 24 hours. At 1 month, the mean EDV decreased 36% (P = 0.0105) and the mean RI increased 3.8% (P = 0.0305) in the nasal PCA. Although there was a similar trend in the temporal PCA, the differences did not reach statistical significance. In the central retinal artery (CRA), the mean PSV decreased 16% (P = 0.0137), and the mean EDV decreased 21% (P = 0.0222) at 24 hours after treatment. There were no statistically significant differences in the CRA blood flow indices at 1 month after treatment. In the ophthalmic artery, there were no statistically significant differences observed in the mean PSV, EDV, or RI at 24 hours or 1 month after treatment.
CONCLUSIONS. TTT is associated with transiently decreased volumetric blood flow in the retinal circulation 24 hours after treatment. In the posterior ciliary arteries that supply the choroid, there were no changes observed at 24 hours, but at 1 month, there was a decrease in the mean EDV and an increase in the RI in the nasal and temporal PCAs, reaching statistical significance in the nasal PCA only. This study suggests that TTT could lead to alterations in choroidal blood flow, as assessed by CDI. Further study is warranted.
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Introduction |
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In this study, we evaluated the ocular blood flow in subjects before and after they underwent TTT to descriptively analyze the effect of TTT on ocular perfusion. Eleven subjects with occult subfoveal CNVM were assessed by color Doppler imaging (CDI) within 24 hours before, 24 hours after, and 1 month after undergoing TTT. This ocular perfusion assessment before and after TTT has not been performed previously. It should be noted that this study was not designed to assess the efficacy of TTT; this is under evaluation in a large, prospective, randomized trial, as discussed earlier.
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Methods |
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Subjects were deemed ineligible if they had a history of diabetic retinopathy, ophthalmic or retinal artery occlusion, retinal vein occlusions, hypertensive retinopathy, choroidopathy, or known history of significant carotid stenosis. In addition, no subjects were using warfarin at the time of the study and no subject had a history of vasculitis. Additional exclusion criteria for both study and control subjects included glaucoma, optic neuropathy, macular dystrophies, ocular inflammatory disease, retinal detachment, or media opacity sufficient to preclude examination and follow-up. In addition, subjects were excluded if they were unable to give informed consent or had a history of allergy to fluorescein, radiographic dyes, shellfish, or iodine.
Eligible subjects were asked to sign an informed consent before undergoing angiography, CDI, and TTT. Each subject was evaluated before and after TTT to compare pretreatment with posttreatment CDI measurements to evaluate the short-term longitudinal effect on ocular perfusion. In particular, 11 subjects with occult subfoveal CNVM were assessed by CDI within 24 hours before, 24 hours after, and 1 month after undergoing TTT. The pretreatment CDI measurements therefore functioned as a baseline control, with which the posttreatment CDI measurements were compared in a longitudinal fashion.
Color Doppler Imaging
A CDI system (Quantum 2000; Siemens Quantum, Inc., Issaquah, WA)
with a 7.5-MHz linear probe was used to perform all measurements. This
system analyzes a sample of pulsed Doppler signal from within a small
sample volume (1.2 x 1.2 mm) to calculate blood flow velocities.
Ultrasonographic evaluation was performed by an experienced
ultrasonographer who was masked to each subject’s treatment status.
The evaluation was initiated with a CDI of the optic nerve, which provides the most useful landmark for the identification of the several retrobulbar vessels. The ophthalmic artery (OA) is situated either above or below the optic nerve in the posterior orbit, before passing forward in the nasal orbit in a horizontal plane slightly superior to that of the optic nerve. This vessel was examined approximately 25 mm behind the globe in the straighter portion of the vessel in the nasal orbit where the most reliable results are obtained. The central retinal artery (CRA) is detectable within the retrolaminar portion of the optic nerve for approximately 10 mm. In this region the vessel maintains a straight course and angle-of-incidence corrections may readily be applied. Together with the central retinal vein, the artery yields a band of blue and red pixels within the optic nerve shadow, at an angle approximately 15° to the anteroposterior meridian. This technique was consistently applied to both the control and study subjects to evaluate these vessels. The short posterior ciliary arteries (PCAs) commence as trunks approximately 10 to 20 mm behind the globe. It is at this point, before these vessels form multiple branches surrounding the optic nerve in its retrobulbar portion, that operator detection is most reproducible, and this area was consequently chosen as a CDI study locus. It is possible to identify and reliably assess the nasal and temporal posterior ciliary vessels, and these vessels were therefore studied in all subjects.
In each vessel, PSV and EDV were calculated from the Doppler signal. PSV refers to the highest blood flow velocity achieved during systole and is calculated from the frequency of the peak in the Doppler-shifted waveform. EDV refers to the lowest velocity occurring during diastole and is calculated for the frequency of the trough in the waveform. In addition, the Pourcelot resistance index (RI), a measure of peripheral vascular resistance, was calculated for each vessel. RI is calculated as: RI = (PSV - EDV)/PSV. Paired t-tests were used to compare PSV, EDV, and RI in each vessel before and after treatment.
Transpupillary Thermotherapy
TTT was delivered through a slit lamp using an infrared (810 nm)
diode laser photocoagulator with a beam diameter adjustable from 0.5 to
3.0 mm (IRIS Medical OcuLight SLx; Iridex Corp, Mountain View, CA).
A standard Goldmann-type fundus contact lens, antireflective
(AR)-coated for use with the diode laser, was placed on the
eye after topical anesthesia with 0.5% proparacaine. Continuous
observation through the slit lamp was maintained to ensure fixation and
the absence of ophthalmoscopically apparent chorioretinal change during
treatment.
Treatment was initiated with one 3.0-mm diameter spot for a 60-second duration and a power setting of 800 mW. If a retinal color change was observed, treatment was immediately stopped and restarted at a reduced power setting (20% decrements) to complete the full 60-second treatment. In general, there was no color change seen as a treatment endpoint, or there was a barely detectable light-gray appearance to the lesion.
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Results |
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In the CRA, the mean PSV measured 9.208 ± 1.974 cm/sec 24 hours before treatment and 7.689 ± 1.418 cm/sec 24 hours after treatment, yielding a 16% decrease, which was statistically significant (P = 0.0137). The mean EDV in the CRA measured 2.117 ± 0.690 cm/sec before treatment compared with 1.681 ± 0.477 cm/sec at 24 hours after treatment, yielding a 21% decrease (P = 0.0222). There was no statistically significant difference in the CRA RI at 24 hours after treatment. Consequently, this concurrent decrease in the PSV and EDV at a constant RI implies decreased volumetric blood flow in the CRA at 24 hours after treatment. This decrease was not sustained, however; there were no statistically significant differences in the CRA blood flow indices at 1 month after treatment.
In the ophthalmic artery, there were no statistically significant differences observed in the mean PSV, EDV, or RI at 24 hours or 1 month after treatment.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The present study revealed statistically significant differences in the retrobulbar blood flow indices in the CRA at 24 hours and in the nasal PCA at 1 month. In the CRA, there was a concurrent decrease in the PSV and EDV at a constant RI, implying decreased volumetric blood flow in the CRA at 24 hours after treatment. This decrease was not sustained, however, at 1 month after treatment. As noted, the infrared wavelength of TTT is absorbed maximally by the deep choroidal tissues and minimally by the retina. Consequently, it is unclear whether this transient alteration in retinal blood flow represents an unanticipated direct effect on the retinal circulation or a secondary autoregulatory process by the retinal circulation.
In the posterior ciliary arteries, which supply the choroid, there were no changes observed at 24 hours, but at 1 month, there was a decrease in the mean EDV and an increase in the RI in the nasal and temporal PCA, reaching statistical significance in the nasal PCA only. It is possible that a larger sample size would have led to statistical significance in the temporal PCA as well. Alternatively, it is possible that there is regulatory shunting of blood from the nasal to the temporal choroid in response to TTT, leading to preferential alterations in the nasal choroidal circulation.
The mechanism by which TTT leads to alterations in choroidal blood flow is unclear. However, if TTT leads to complete or partial occlusion of occult CNVM, choriocapillaris, or both, then an increase in the RI would be expected. Unfortunately, it is difficult to accurately assess blood flow through the CNVM, before and after TTT, for several reasons. In particular, it is very difficult to quantify choroidal blood flow angiographically, given the overlying retinal and multilayered choroidal circulations that complicate analysis. In addition, the limited sample size of this study prevents meaningful analysis of the angiograms with respect to perfusion of the occult CNVM and choriocapillaris. Although this study suggests that TTT can lead to alterations in choroidal blood flow, which may be consistent with complete or partial occlusion of occult subfoveal CNVM as suggested by other investigators,1 further study is warranted.
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Footnotes |
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Submitted for publication January 16, 2001; revised June 19, 2001; accepted August 6, 2001.
Commercial relationships policy: N.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be marked
"advertisement" in accordance with 18 U.S.C. 
1734
solely to indicate this fact.
Corresponding author: Thomas A. Ciulla, Retina Service, Department of Ophthalmology, 702 Rotary Circle, Indiana University School of Medicine, Indianapolis, IN 46260. tciulla{at}iupui.edu
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References |
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