Thursday 27 September 2012

Combined Fluorescein, Indocyanine angiography and Optical coherent tomography using Spectralis By Manish Nagpal,MS., DO., FRCS (UK); Navneet Mehrotra,DNB



Editor                                  
Dr Sudhir Singh
 
Advisors
Prof. P.K Mathur
Dr  Pavan Shorey
 
Editorial Board
Dr Anshoo Choudhary
Dr Arun Kshetrapal
Dr L S Jhala
Dr Mayank Agrawal
Dr Mukesh Sharma
Dr Sandeep Arora
Dr Sonu Goel
Dr Subodh Saraf
Dr Sukesh Tandon
Dr Sunil Gupta
Dr Suresh Kumar Pandey
Dr Swati Tomar
Dr Virendra Agrawal
 


Combined Fluorescein, Indocyanine angiography and Optical coherent tomography using Spectralis 
Manish Nagpal,MS., DO., FRCS (UK); Navneet Mehrotra,DNB
Corresponding Author
Dr  Manish Nagpal,
MS., DO., FRCS (UK) 
Retina Foundation
 Near Shahibag Underbridge
 Shahibag, Ahmedabad - 4
 Gujarat, India
drmanishnagpal@yahoo.com 
Article Code RJO20110101
Introduction
Fluorescein angiography remains, since its inception, nearly mandatory for diagnosis and management of a large number of retinal disorders. It abets in visualization of the retinal and choroidal vasculature. FA is valuable in accurate imaging of the retinal circulation. Furthermore, it allows identification of the leakage sites of the small fluorescein molecule in pathological states affecting the retinal vasculature. However, it’s obvious inherent limitations towards imaging of the choroidal circulation led to the development of infrared angiography using indocyanine green (ICG) dye, which was introduced in 1980’s.
 ICG delineates the choroidal circulation in the better way. The dye absorbs and emits light in the near – infrared spectrum, allowing better penetration through the retinal pigment epithelium and extraneous absorbing material such as exudates and hemorrhages. Secondly, the molecule is larger (molecular weight 775 D versus 332 D for fluorescein) and more protein bound in the plasma, so it does not leak from the choriocapillaris as sodium fluorescein dye normally does.
Optical Coherence Tomography (OCT) is a non-contact imaging technology in which reflected light is used to produce detailed cross-sectional and 3D images of the eye.
An early version of this technology, time-domain OCT (TD-OCT), uses a moving reference mirror for measuring the time it takes for light to be reflected. This relatively slow, mechanical process limits both the amount of data that can be captured as well as image quality. TD-OCT data is acquired at approximately 400 axial scans, or A-scans, per second. The newer Spectral (or Fourier)-domain OCT (SD-OCT) uses a significantly faster, non-mechanical technology. The SD-OCT simultaneously measures multiple wavelengths of reflected light across a spectrum, hence the name spectral-domain. The SPECTRALIS system is 100 times faster than TD-OCT and acquires 40,000 A-scans per second. The increased speed and number of scans translates into higher resolution and a better chance of observing disease.
Scanning laser ophthalmoscopy is a retinal imaging technique that is based on the standard scanning laser microscope. Scanning laser ophthalmoscopes, when equipped with a confocal aperture, offer fundamentally better performance than conventional imaging instruments. The confocal SLO generates high contrast images and can do optical slicing through weakly scattering media making it ideal for imaging the multilayered retina.
Mechanism of  angiogram with CSLO
The laser sources are focused onto the retina. Oscillating mirrors provide horizontal and vertical beam scanning. Spherical aberrations are compensated in the range of +/-12D.the system uses a 3mm illumination beam aperture and the full aperture of the dilated or undilated eye to collect the emitted fluorescence light. The size of the square scan field can be set to 10x10 degrees, 20x20 degrees, and 30x30 degrees.
By using a diode laser for ICG-A, as well as suitable filters for detecting fluorescence emission, the HRA can be use to acquire FA images, ICG-An images, OCT images or simultaneous fluorescein and ICG-An images and with OCT images. In the simultaneous angiography mode, image pairs are acquired at the same time, and both live images are displayed side by side on the monitor. Two laser light sources with three wavelengths for scanning fundus illumination are used. Maximal retinal irradiation at 30 degrees is 1.6mW/cm2, well below the limits established by American National Standard Institute and the other international standards. Two scanning mirrors provide the horizontal and vertical scanning directions. The illumination beam has a diameter of 3 mm, and the full aperture of the dilated or undilated eye is used to collect light from the posterior pole. The field of view can be variable. The confocal detection unit employs a small (400µ) pinhole aperture to suppress light originating from below or above the focal plane.
For simultaneous FA and ICG-A, the laser radiation is deflected by means of a resonant scanner so that the two are done quasi-simultaneously. The infrared laser is guided onto each line scan, and the blue radiation is applied during the return movement of the scanning mirror. Images are digitized upto the rate of 20 frames per second with the time separation between corresponding lines of two angiograms being in the order of 0.1ms. Each frame contains 256 pixels vertically, 256 pixels horizontally and 8 bit per pixel intensity quantitation. During examination, both FA and ICG A  angiograms are displayed simultaneously on the monitor. The images are stored digitally in the RAM of the computer during acquisitionand subsequently transferred to the hard disk. Dynamic high speed angiography is used for real timeimaging where the maximum frame rate of 50 frames/ sec is possible. This allows temporal resolution of of the choroidal transit, which has a duration of less than 2 seconds. This is especially important in the early stages of FA and ICG-A and enables better detection of CNV characteristics such as feeder vessels. Infrared images can also be acquired simultaneously with either FA or ICG A. Exceptionally high quality late stage image scan be obtained without a second landmark injection, which is necessary when using a standard fundus camera. Composite images (upto 120 degrees) can be easily produced in a few seconds by automatically combining multiple images taken of the posterior pole and the periphery.
The light intensity during simultaneous FA and ICG A is balanced by independently adjusting detector sensitivity for fluorescein fluorescence and laser power for indusing ICG fluorescence. The laser used for ICG A is working at upto 2mW radiation power, whereas the laser power for FA is fixed at 300 µW.In simultaneous acquisition , every horizontal scan line is illuminated with the two lasers one after the other, while the same detector electronics is used for both lines. The light detecting unit is Avalanche photo diode (APD), which is approximately three times more sensitive to 788nm compared to 488nm. Because of the increased light power for the ICG and the higher sensitivity of the detector system, ICG A pictures are brighter than FA images. TO acquire both the with proper brightness, the detector sensitivity is adjusted to the FA images, whereas the brightness of the ICGimages is adjusted by diminishing the laser power for ICG.
Simultaneous angiograms and OCT
It is known that both studies are needed for diagnosis and localization of difficult cases. Single combined intravenous injection of fluorescein and ICG dyes can be used to get both images.. It needs a special system with both FA and ICG excitation systems, which is possible with Heidelberg retinal angiograph (HRA) (Heidelberg Engineering Inc., Heidelberg, Germany)
 The most obvious advantage of truly simultaneous imaging is the negation of the possibility that one of the angiogram is of the higher quality as compared to the other, which may lead to differences in visualization of the pathological states. The potential reasons that one study might be of better or of differing quality than the other include differences in centering, patient movement, continuous eye movements, focus, exposure and blinking. These factors decrease the significance of the relative differences between the two films. An exact overlap of the transit of the two dyes despite the ever variable external factors is only possible if the images are acquired simultaneously.
 The other significant advantage of the simultaneous angiography technique is the time sequence correlation. Both the dyes are injected and, therefore, imaged simultaneously. Therefore, the physiological differences in their distribution and circulation through the eye are easily discernible. Furthermore, the differences in response to the pathological states of the retinal and choroidal circulation are made obvious and are readily compararble. Thus, the relative value of each type of dye in normal physiology and different disease processes becomes apparent, which is relevant for both clinical and research purposes.
 Lastly the time required to perform the entire study is considerably shorter. Patient compliance and investigator‘s ease are noteworthy.
HRA has an added advantage of simultaneously carrying out the OCT with FA or ICG. It gives an additional information of the pathology. The ability to scan images at 40 kHz helps reduce eye movement artifacts and increases patient comfort, providing cleaner images. TruTrack image alignment technology provides eye tracking and guiding of the SD-OCT. This feature aligns images in the same exam and finds the same location in subsequent exams to track subtle changes over timeVarious pathologies in which  simultaneous angiograms with OCT may be of benefit have been discussed.
 Age related macular degeneration
ICG angiography is an important adjunctive study to FA in the detection of CNV. The medium and larger proliferating choroidal vessels may be better imaged by ICG angiography. If more than one well-defined areas of occult CNV is seen, this is termed as multifocal. FA may image well-defined CNV better than ICG angiography in some cases; however, in many patients ICG angiography can convert occult CNV shown by FA into classic CNV. It appears that the best imaging strategy for detecting CNV is to perform both FA and ICG angiography.ICG videoangiography can successfully guide laser photocoagulation of occult CNV.
With today’s trend towards pharmacologic therapy for exudative CNVM, accurate angiographic classification of CNVM is not essential in determining treatment. However, response to pharmacologic therapy is not uniform among patients, and various studies suggest classic and occult CNVMs may have different prognosis and natural course. Simultaneous FA or ICG with OCT may help to determine whether a correlation exists between the growth pattern and morphologic changes associated with CNVM and response to pharmacologic therapy. 
Figure 1: Choroidal vessels better imaged by ICG than FA
Figure 2 : Occult CNVM on fluorescein angiography
Figure 3 : Simultaneous FA and OCT
Idiopathic polypoidal choroidal vasculopathy

IPCV is often seen in middle-aged women of Asian-African ancestry and is also known as the posterior uveal bleeding syndrome. It is a primary abnormality of the choroidal circulation in which a network of vessels terminate in polypoidal or aneurysmal excrescences at the level of the choroid. This is visible clinically as a reddish orange mass.
ICG angiography is sensitive and specific in the accurate detection and characterization of this abnormality. The initial phase reveals a distinct network of vessels within the choroid that start to fill before the retinal vessels, fill more slowly than the retinal vessels, but this area is hypofluorescent as compared to the surrounding choroid. The hyperfluorescent "polyps" that become visible within the choroid correspond to the clinically visible reddish orange choroidal excrescences
High-resolution OCT images demonstrate that polypoidal structures exist beneath RPE and attach at the back surface of RPE.
Simultaneous ICG and OCT revealed  that the leakage from the polypoidal lesions detaches the RPE, and the polypoidal lesion resides beneath the PED.
Figure 4 : Polyp like growth seen in ICG

Figure 5 : Simultaneous ICG and OCT
CSR
On combined FA and ICG A, ICG A tends to reveal a much larger area of pathology in the choriocapillary pigment epithelium region as compared to the FA.
Figure 6 : Pigmentary changes seen more in ICG than FA
 
Figure 7 : Simultaneous FA and ICG
Figure 8 : Simultaneous FA and OCT showing PED
Figure 9 : Simulataneous FA and OCT showing hyperreflectivity in the subsensory space
The development of OCT has provided a better understandingof the mechanism in CSC, especially the abnormalities in the RPE layer. We observed RPE abnormalities in
95% of eyes with acute CSC and clearly visualized a minute defect of the RPE within the PED, which seemed to correspond precisely to the leakage point on FA. When the retina detached, the appearance of the outer retinal layer changed; the external limiting membrane persisted, although the IS/OS could not be detected in all eyes, as recently reported by Ojima et al. In the acute phase, the thickness of the probable photoreceptor outer segment increased in the entire area of the detached retina. The increased thickness of the photoreceptor outer segment in the detached retina then gradually decreased, and the outer segment’s appearance changed to granular until the reattachment.
 CHOROIDITIS
ICGA images have been helpful to know  histopathology  for some of the diseases such as the primary stromal choroiditides Vogt-Koyanagi-Harada disease, sympathetic ophthalmia and birdshot chorioretinopathy  Indocyanine green angiography showed occult choroidal lesions not shown by fundoscopy and/or fluorescein angiography
Indocyanine Green angiography is useful for identification and staging of new active lesions of serpiginous like choroiditis. The area of choroidal nonperfusion seen by ICG during the acute stage is generally larger than the corresponding clinically observed retinal lesions. The ICG is also useful in detecting subclinical or persistent choroidal nonperfusion even when the signs of retinal activity have disappeared.
Figure 10 : Area of choroidal non perfusion more on ICG than FA
Figure 11 : Simultaneous FA and ICG in a case of serpigenous  like choroiditis showing pigmentary changes
Figure 12 : FA ICG in a case of serpiginous like choroiditis
Figure 13 : Large choroidal vessels seen in ICG in a case of serpiginous like choroiditis
 ICG in VKH disease showed (1) early choroidal stromal vessel hyperfluorescence and leakage, (2) hypofluorescent dark dots, (3) fuzzy vascular pattern of large stromal vessels and (4) disc hyperfluorescence (5) pin point hyperfluorescent dots
Figure 14: Hypofluorescent dark dots in ICG
 
Figure 15: Leakage from choroidal vessels seen in ICG
OCT in cases of VKH showed serous retinal detachments which corresponded with leakage in fluorescein and ICG angiography. Other findings include focal atrophic areas, subretinal fibrosis and  cystoid macular edema.
Figure 16: Simultaneous FA and OCT in a case of VKH
Figure 17: Simultaneous ICG and OCT
In patients with granulomas FA shows leakage with granular hyperfluorescence at the same phase as ICG shows hypofluorescence. OCT showed subsensory fluid and thickening at the level of choroid.
Figure 18: Simultaneous FA and OCT in a case of choroiditis
 
The Rajasthan Journal Of Ophthalmology An Official Publication Of TheRajasthan Ophthalmological Society
 
 
Chief Web Editor Dr Sudhir Singh
All Rights Are Reserved To Rajasthan Ophthalmological Society

No comments:

Post a Comment