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ORIGINAL ARTICLE
Year : 2015  |  Volume : 28  |  Issue : 4  |  Page : 902-907

Correlation of optical coherence tomography and fluorescein angiography imaging in neovascular age-related macular degeneration


Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission06-Sep-2014
Date of Acceptance11-Jan-2015
Date of Web Publication12-Jan-2016

Correspondence Address:
Asmaa Z Fadel
Gamal Abd-El-Naser, Shibin El-Kom, Menoufia, 32512
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.173611

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  Abstract 

Objectives
The aim of this work was to study the role of fundus fluorescein angiography and spectral domain optical coherence tomography (SDOCT) in the diagnosis of wet age-related macular degeneration (AMD).
Background
AMD is the leading cause of severe visual impairment in elderly people. Various imaging methods are available for the diagnosis and the classification of AMD. Fluorescein angiography (FA) is the gold standard for the differential diagnosis of neovascular AMD and determination of lesion characteristics. SDOCT is used for the diagnosis and the follow-up of patients with neovascular AMD undergoing antivascular endothelial growth factor therapy, by providing high-resolution cross-sectional images of retinal pathology.
Participants and methods
This study included 30 patients divided into three groups: group Me, patients with dry AMD; group II, patients with wet AMD divided into classic choroidal neovascularization (CNV) and occult CNV; group III, patients with geographic atrophy. All participants underwent a full ophthalmologic evaluation, including dilated fundus examination by binocular indirect ophthalmoscope. Slit-lamp biomicroscopy was performed using the Goldman three mirror lens and Volk 78 lens; also, the best-corrected visual acuity was measured with the Landolt chart and converted to the logarithm of the minimum angle of resolution (logMAR) units, and fundus fluorescein angiography and then optical coherence tomography (OCT) were performed.
Results
Using SDOCT imaging to delineate the lesion morphology, early AMD was detected by the presence of a normal foveal contour and minimal alteration in the macular area, classic CNV by the presence of a well-defined lesion with steep margins and a crater like configuration, and occult CNV by the presence of an ill-defined, flat lesion with a convex surface. FA-OCT overlay images provided a significant correlation between FA patterns and OCT features such as retinal pigment epithelium (RPE) complex changes. The sensitivity of cases with dry AMD in FA to cases with undulation in OCT was 100%, the specificity was 92%, the accuracy was 93%, the positive predictive value (PPV) was 75%, and the negative predictive value (NPV) was 100%. The sensitivity of cases with wet AMD in FA to cases with thickening in OCT was 96%, the specificity was 20%, the accuracy was 83%, the PPV was 86%, and the NPV was 50%. The sensitivity of cases with geographic atrophy of AMD in FA to cases with thinning in OCT was 100%, the specificity was 97%, the accuracy was 97%, the PPV was 50%, and the NPV was 100%.
Conclusion
SDOCT is highly sensitive for identifying AMD, CNV, and CNV activity, but cannot fully replace FA in the diagnosis of AMD.

Keywords: choroidal neovascularization, fluorescein angiography, spectral domain optical coherence tomography


How to cite this article:
El-Sadany AKI, Marey HM, El-Sawy MF, Fadel AZ. Correlation of optical coherence tomography and fluorescein angiography imaging in neovascular age-related macular degeneration. Menoufia Med J 2015;28:902-7

How to cite this URL:
El-Sadany AKI, Marey HM, El-Sawy MF, Fadel AZ. Correlation of optical coherence tomography and fluorescein angiography imaging in neovascular age-related macular degeneration. Menoufia Med J [serial online] 2015 [cited 2024 Mar 28];28:902-7. Available from: http://www.mmj.eg.net/text.asp?2015/28/4/902/173611


  Introduction Top


Age-related macular degeneration (AMD) is the leading cause of severe visual impairment in elderly people in industrialized countries [1],[2] . Epidemiologically, the disease is gaining importance, as the life expectancy of the elderly population is increasing continuously [3],[4] .

Fluorescein angiography (FA) is the gold standard for the differential diagnosis of neovascular AMD and the determination of lesion characteristics. On the basis of FA, neovascular AMD is classified according to the form into predominantly classic, minimally classic, and occult [5] .

FA evaluation is less informative as occult components may not be clearly detected and delineated, and the intensity and the extent of the active leakage cannot be measured precisely. Moreover, optical coherence tomography (OCT) easily differentiates between leakage and staining as the hyperfluorescence induced by the latter represents visualization of fibrotic tissue and not edema, which appears as a thickening of the hyper-reflective RPE band on OCT [5].

This study aimed to determine the correlation of OCT and FA imaging in neovascular AMD.


  Participants and methods Top


This study included cases of neovascular AMD. They were enrolled from the ophthalmic outpatient clinic of the Faculty of Medicine, Menoufia University, between April 2013 and May 2014. The local ethical committee at Menoufia University Hospital approved the study protocol, and an informed consent was obtained from all participants before commencing the study.

A total of 30 patients of 22 men and eight women with a mean age 68.26 years (±8.84 SD) were included in this study and divided into three groups:

Group I: dry AMD;

Group II: wet AMD;

Group III: geographic atrophy (GA) of AMD.

All patients underwent a full ophthalmologic evaluation including dilated fundus examination by binocular indirect ophthalmoscopy.

Slit-lamp biomicroscopy was performed using Goldman three mirror lens, Volk 78 lens; also, the best-corrected visual acuity was measured with the Landolt chart and was converted to the logarithm of the minimum angle of resolution (logMAR) units for statistical analysis, and fundus fluorescein angiography (FFA) and then OCT were performed.

Optical coherence tomography technique

Spectral domain optical coherence tomography (SDOCT) (Heidelberg engineering) was used for all patients.

The Spectralis SDOCT (Heidelberg Engineering, Heidelberg, Germany) simultaneously measures multiple wavelengths of reflected light across a spectrum, and 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.

Fluorescein angiography technique

An intravenous injection of 5 ml 10% sodium fluorescein was injected rapidly into an anticubital vein.

A digital retinal camera system (Topcon TRC-50 EX with volt 120.220.240 V and power normal 150 VA, maximum TRC-50 EX/FREQ.50/60 Hz; Tokyo, Japan) was used for FA examination after pupil dilatation.

Statistical analysis

Results were collected, tabulated, statistically analyzed by an IBM personal computer and the statistical package SPSS version 20 (SPSS Inc., Chicago, Illinois, USA). Two types of statistics were performed.

  1. Descriptive statistics: for example, percentage (%), range, mean, and SD.
  2. Analytical statistics:
    1. Fisher's exact test: It was used to compare two or more groups regarding one qualitative variable in a 2 × 2 contingency table when the count of any of the cells was less than 5.
    2. Sensitivity or the true positive rate = true positive/(true positive+false negative).
    3. Specificity or the true negative rate=true negative/(true negative + false positive) = 1−false positive rate.
    4. Accuracy = (true positive) + (true negative)/(positive+negative).
    5. Positive predictive value (PPV): True positive/(true positive+false positive).
    6. Negative predictive value (NPV): True negative/(true negative+false negative).



  Results Top


In this group study, sensitivity was defined as the percent of cases with hyperfluorescent drusen with FFA to cases with undulation in OCT, which was 100%; specificity was defined as the percent of cases with absent hyperfluorescent drusen with FFA to cases with absent undulation in OCT, which was 92%; the PPV was 75%, and the NPV was 100%. Also, there were six cases of true-positive and no false-negative results ([Table 1]).
Table 1 Validity of fluorescein angiography (early age-related macular degeneration) according to optical coherence tomography results (undulation)


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In group II, the sensitivity of wet AMD in FA regarding the thickening in the OCT was 96%, whereas the specificity was 20%, the accuracy was 83%, the PPV was 86%, and the NPV was 50% ([Table 2]).
Table 2 Validity of fluorescein angiography (wet age-related macular degeneration) according to optical coherence tomography results (thickening)


Click here to view


Also, the percent of cases with classic choroidal neovascularization (CNV) was 83.3%, the percent of cases with occult CNV was 16.7%, and the P value was 1.0 ([Table 3]).
Table 3 Fluorescein angiography (wet age-related macular degeneration) according to optical coherence tomography results (thickening)


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With respect to this study, in group III, the sensitivity of GA was 100%, which was defined as the percent of cases with GA of AMD (window defect) with FFA to the number of cases with thinning in the OCT, whereas the specificity, defined as the percent of cases with absent GA of AMD with FFA to cases with absent thinning in OCT, was 97%, the accuracy was 97%, the PPV was 50%, and the NPV was 100% ([Table 4]).
Table 4 Validity of fluorescein angiography (geographic atrophy in age-related macular degeneration) according to optical coherence tomography results (thinning)


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  Discussion Top


AMD was considered as the leading cause of severe visual loss and blindness in the developed world among people over the age of 50 years. Various imaging methods are available for the diagnosis and the classification of AMD [6] .

SDOCT is increasingly used in clinical trials and in clinical practice for the diagnosis and the follow-up of patients with neovascular AMD undergoing antivascular endothelial growth factor therapy. As a noninvasive imaging tool, it provides high-resolution cross-sectional images of the retinal pathology, allowing one to analyze qualitatively and quantitatively various parameters relevant for (re-) treatment decisions [7] .

FA is commonly used as the gold standard for evaluating CNV lesions. On the basis of FA, CNV lesion components are categorized as classic or occult CNV leakage or staining scar tissue that may develop over time and indicate longstanding disease with poor visual function [8] .

In a study conducted by Nils and colleagues, 75 eyes were diagnosed with AMD on the basis of fundus photography (FP). Signs of AMD were detected on FA in 77 eyes with a sensitivity of 92% (69 out of 75) and a specificity of 82% (in eight cases, AMD was noted on FA, but not on color fundus photographs).

On SDOCT, AMD was considered present, with a sensitivity of 78% (53 out of 68 eyes) for the detection of CNV and a specificity of 100%. SDOCT images showed signs of CNV in 64 out of the 68 cases (94%), and the specificity for detecting CNV was 98% (in one case, CNV was diagnosed on the basis of SDOCT, but not on FA) [9] .

This study approved that SDOCT, FA, and FP imaging provide complementary information about pathological changes in chorioretinal disease, and SDOCT is highly sensitive to identify CNV and CNV activity; however, it cannot fully replace FA in the management of patients with CNV [9] .

However, in our study, the number of cases with early AMD in FA and undulation in OCT was six (true positive), the number of cases with early AMD in FA but no undulation in OCT was two (false positive), and the number of cases with absent early AMD in FA or undulation in OCT was 22, and so, early AMD is a good negative test.

The sensitivity of wet AMD, defined as the percent of cases with wet AMD with FA to the cases with OCT, was 96%, the specificity, defined as the percent of cases without wet AMD in FFA to cases without wet AMD in OCT, was 20%, and the accuracy was 83%.

In our study, 20 cases with classic CNV was demonstrated with FA and OCT, at 83.3%, and the number of cases with occult AMD was four in both FA and OCT, at 16.7%.

In our study, we correlated FA and SDOCT in the diagnosis of wet AMD and dry AMD, whereas the study conducted by Nils and colleagues compared FP, FA, and SDOCT for the detection of AMD, CNV, and CNV activity.

Occult CNV on FA is believed to correspond histologically to type 1 CNV, located between the RPE and Bruch's membrane [10] . In accordance with this, eyes with occult CNV demonstrated a pigment epithelium detachment on SDOCT in the study conducted by Nils and colleagues, and these results are in agreement with our study.

In contrast, classic CNV lesion components on FA histologically correspond to type 2 CNV, positioned in the subretinal space [10] . Thus, type 2 CNV lesion components are demonstrated as hyper-reflective material in the subretinal space on OCT in the study conducted by Nils and colleagues, and these results are in agreement with our study.

Nils et al. [9] approved the fact that FA is used to obtain information about the perfusion and the growth of new vessels and the integrity of the blood retinal barrier; thus, fluorescein leakage over time can be seen during angiography.

This information is missing in OCT images. Thus, OCT provides detailed information about pathological changes such as the presence of cystoids spaces; however, it is not possible to detect whether they are caused by fluid accumulation from acute leakage from pathological vessels [9] , and this is in agreement with our study.

Also, the study conducted by Panagiotis et al. [5] evaluated the ability of three-dimensional SDOCT imaging to distinguish among the characteristic types of AMD, even from early changes in the neovascular disease, and to define lesion characteristics on the basis of lesion components and correlated with those of conventional FA, and this was in agreement with our study.

In the study conducted by Panagiotis et al. [5] , the standard methods practiced to evaluate CNV-related disease remain FA, indocyanine green angiography, and OCT.

In the study conducted by Malamos and colleagues, the instrument used was high-definition OCT, whereas in our study, it was spectral-domain OCT. Also, in our study, the subgroups included dry AMD and wet AMD, which is divided into classic, occult, and GA of AMD, whereas in the study conducted by Malamos and colleagues, the subgroups included early AMD and wet AMD, which were divided into predominantly classic, minimally classic, and occult CNV; also, the retinal thickness was measured in their study, whereas in our study, the retinal thickness not measured [11] .

In the study conducted Tomi [12] , AMD in general was discussed, whereas our study mainly discussed cases of neovascular AMD.

FA highlights the features of classic and occult lesion components and extravasation originating from leaky neovascular channels in a qualitative way. In contrast, OCT offers the complementary ability of imaging the retinal structures and the level of retinal involvement by the CNV [13] .

In GA, there is increased FA from window defect, and SDOCT has shown central choroidal hyper-reflectivity from absent RPE blockage [14],[15],[16] .

In our study, GA appeared in FA as a window defect due to RPE atrophy, whereas in OCT, it appeared as retinal thinning, and this agrees with the study conducted by Raimondo et al. [17] in which a digital retinal camera and an SDOCT system combined with a multimodal cSLO topographic imaging system was used to obtain color fundus photographs and simultaneous recordings of cross-sectional SDOCT and cSLO images, to correlate FA, near-infrared reflectance, fundus autofluorescence (FAF), and near-infrared autofluorescence images and to understand the clinical significance of near-infrared reflectance, FAF, and near-infrared autofluorescence in dry AMD, whereas in this study, only FA and OCT results were correlated together for the diagnosis of dry AMD and neovascular AMD.

With respect to our study, the number of cases with GA of AMD in FA and in OCT was one (true positive), the number of cases with GA of AMD in FA and absent in OCT was one (false positive), and the number of cases with absent GA in both FA and OCT was 28 (good negative test).

The sensitivity of FA regarding OCT was 100%, the specificity was 97%, and the accuracy was 97%.

In our study, SDOCT is highly sensitive for the detection of AMD and CNV; however, it cannot fully replace FA. This finding was in agreement with the study conducted by Nils et al. [9] ([Figure 1], [Figure 2], [Figure 3]).
Figure 1 (a) A fundus photograph showed a central pale yellow macular lesion with macular drusen temporarily. Fluorescein angiography (FA) revealed a picture of wet age-related macular degeneration (AMD) of the classic type with hyperfluorescent drusen. (b) Optical coherence tomography (OCT) examination showed increased thickness and hyper-reflectivity of the RPE complex, with diffuse macular edema and loss of foveal contour.

Click here to view
Figure 2 (a) Fundus photograph showed central pale yellow macular lesion with FA revealed a picture of wet AMD of classic type. (b) Optical coherence tomography (OCT) examination showed increased thickness and hyper-reflectivity of the RPE complex, with diffuse and cystoid macular edema and loss of foveal contour.

Click here to view
Figure 3 (a) A fundus photograph showing the area of RPE atrophy at the macular region. Fluorescein angiography (FA) revealed a picture of dry age-related macular degeneration (AMD) [geographic atrophy (GA)] with hyperfluorescent drusen. (b) Optical coherence tomography (OCT) examination showed thinning of the hyper-reflective RPE complex and loss of foveal contour.

Click here to view



  Conclusion Top


AMD is the leading cause of vision loss. Early detection and treatment is required. AMD is diagnosed by fundus examination, FA, and OCT. SDOCT and FA imaging provide complementary information about pathological changes in chorioretinal diseases. SDOCT is highly sensitive for identifying AMD, CNV, and CNV activity; however, it cannot fully replace FA in the diagnosis of AMD.


  Acknowledgements Top


Conflicts of interest

None declared.

 
  References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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