Ophthalmic Surgery, Lasers and Imaging Retina

Instruments/Devices/Technology 

Vascular Features of Full-Thickness Macular Hole by OCT Angiography

Stanislao Rizzo, MD; Alfonso Savastano, MD; Daniela Bacherini, MD; Maria Cristina Savastano, MD, PhD

Abstract

BACKGROUND AND OBJECTIVE:

To compare the features of cystoid cavities associated with full-thickness macular hole (FTMH) imaged with optical coherence tomography angiography (OCTA) and en face OCT.

PATIENTS AND METHODS:

Prospective, observational, cross-sectional study. Clinical practice and observation. Thirteen patients (13 eyes) with FTMH were evaluated before vitrectomy. All eyes underwent OCTA or en face OCT imaging.

RESULTS:

There was a statistically significant positive correlation between groups for the total cavity area in both inner nuclear layer (P < .001; r2 = 0.82) and outer plexiform and Henle fiber layer complex (P < .001; r2 = 0.84).

CONCLUSIONS:

OCTA and en face image of cystoid cavities show very similar features and are complementary for the evaluation of the disease. The OCTA images show “vascular sliding” at the border of the cystoid cavities in FTMH, suggesting preservation of microvasculature surrounding the cystoid spaces during the disease process.

[Ophthalmic Surg Lasers Imaging Retina. 2017;48:62–68.]

Abstract

BACKGROUND AND OBJECTIVE:

To compare the features of cystoid cavities associated with full-thickness macular hole (FTMH) imaged with optical coherence tomography angiography (OCTA) and en face OCT.

PATIENTS AND METHODS:

Prospective, observational, cross-sectional study. Clinical practice and observation. Thirteen patients (13 eyes) with FTMH were evaluated before vitrectomy. All eyes underwent OCTA or en face OCT imaging.

RESULTS:

There was a statistically significant positive correlation between groups for the total cavity area in both inner nuclear layer (P < .001; r2 = 0.82) and outer plexiform and Henle fiber layer complex (P < .001; r2 = 0.84).

CONCLUSIONS:

OCTA and en face image of cystoid cavities show very similar features and are complementary for the evaluation of the disease. The OCTA images show “vascular sliding” at the border of the cystoid cavities in FTMH, suggesting preservation of microvasculature surrounding the cystoid spaces during the disease process.

[Ophthalmic Surg Lasers Imaging Retina. 2017;48:62–68.]

Introduction

The introduction of structural optical coherence tomography (OCT) more than two decades ago has led to significant changes in the understanding and detection of chorioretinal disease. Additionally, structural OCT is becoming the gold standard for the diagnosis and management of vitreoretinal disorders.1 Recently, a new vitreomacular disease classification has been introduced based on the features of structural OCT.2

Recent advances in OCT technology such as coronal scans (transverse scanning, en-face) have allowed detailed evaluation of the retinal pigment epithelium.3

Matet et al. used en face OCT imaging to evaluate the anatomical differences between cystoid cavities in the inner nuclear layer (INL), the outer plexiform (OPL), and the Henle fiber layer (HFL) complex.4 They reported differing cavity patterns based on the retinal layer. These differences were partially attributed to the distribution of Muller cells in the retina.4

The recent introduction of OCT angiography (OCTA)5 allows the noninvasive evaluation of retinal vasculature in different chorioretinal diseases. However, Spaide et al.6 described some potential artifacts of this new imaging modality. Thorough ophthalmic evaluation and comprehensive interpretation of the images can mitigate the potential for misdiagnosis based on OCTA images. Additionally, optical engineering algorithms are generating faster image acquisition techniques with fewer artifacts and easier interpretation of the data.

Currently, OCTA is most commonly used to evaluate neovascular disease,7,8 occlusive diseases,9,10 or the diabetic retina.11 However OCTA can be used for vitreomacular pathologies to evaluate the effect of macular surgery on retinal microvasculature. Investigators and clinicians can evaluate the superficial and deep vascular plexus in vitreoretinal disease using OCTA.12,13 Currently, there are several commercially available optical coherence tomographers. Many of these tomographers performs OCTA with distinct technical features, such as measurement wavelength, segmentation algorithms, size of the image area, normative databases, and measurement reproducibility.14

In clinical application, enface OCT scan allows detailed evaluation of the morphology of tissue involvement, whereas OCTA presents the vascular impairment due to the disease.

The aim of this study was to compare the area of cystoid cavities surrounding full-thickness macular hole (FTMH) with en face and OCTA images using OCTA technology.

Patients and Methods

This prospective, observational, cross-sectional study evaluated 13 eyes of 13 patients with FTMH who were evaluated with OCTA. This study compared the clinical features and cystoid cavity area in OCTA (OCTA group) and en face OCT (en face group) images. This study adhered to the tenets of the current version of the Declaration of Helsinki (52nd WMA General Assembly, Edinburgh, Scotland, October 2000), and written informed consent was obtained from all patients prior to participation in the study. Institutional review board /ethics committee approval was obtained.

Patients were included in the study if they had a FTMH with cystoid cavities organized in INL and the OPL + HFL complex detected with B-scan OCT, were cooperative, and if the images were of adequate quality to define the location of the cystoid cavities. Exclusion criteria were media opacity and concomitant diseases such as diabetic retinopathy, vein or artery occlusion, and glaucoma.

All patients underwent a baseline ophthalmic examination, including medical and ocular history, family medical history, measurement of best-corrected visual acuity (BCVA), slit-lamp examination of the anterior and posterior segments, measurement of intraocular pressure, dilated fundus examination, and axial length measurement with noncontact partial coherence laser interferometry (IOL Master, version 3.01; Carl Zeiss Meditec, Jena, Germany).

The RS-3000 Advance spectral-domain OCT (Nidek; Gamagori, Japan) was used to acquire OCTA and en face images in all eyes. This device uses an 880-nm wavelength and with a scanning speed of 53,000 A-scans/second. A 3 mm × 3 mm (256 × 256 scan points) scanning pattern was performed. All scans were centered on the fovea based on a live scanning laser ophthalmoscopy (SLO) image. All B-scans were performed twice and averaged. A real-time SLO-based active eye tracker was used to compensate for vertical and horizontal movements and cyclotorsion during image acquisition. The mean acquisition time was 96.4 seconds ± 28.2 seconds (range: 57 seconds to 145 seconds). In all cases, the SLO image was captured prior to OCTA analysis.

Scan Selection for Analysis

As the hyporeflective cavities surrounding the FTMH were concentrated within the INL and the OPL + HFL complex, en face OCT scans from these two regions were retained for analysis (Figure 1). For each layer, the scan with the highest quality was selected among those located centrally in the stack. This scan was used to measure the area of the hyporeflective spaces in the frontal plane.


Spectral-domain optical coherence tomography B-scan of a full-thickness macular hole. Manual outline of retinal layers indicates the location of the perifoveal cystoid cavities in the inner nuclear layer (blue) and in the complex consisting of the outer plexiform layer and Henle fiber layer (red).

Figure 1.

Spectral-domain optical coherence tomography B-scan of a full-thickness macular hole. Manual outline of retinal layers indicates the location of the perifoveal cystoid cavities in the inner nuclear layer (blue) and in the complex consisting of the outer plexiform layer and Henle fiber layer (red).

Measurement of Intraretinal Cavity Area

To ensure image comparability between modalities, a 3 mm × 3 mm .jpg image centered on the fovea was extracted from the en face and the OCTA scans. All the images were analyzed using Image J software (Version 1.49v; National Institutes of Health, Bethesda, MD) as previously described.4 Briefly, after conversion to 8-bit images, hyporeflective spaces were identified by the “adjust threshold” function with intensity threshold set from 0 to 45 for en face images and from 0 to 15 for OCTA images.

The resulting binary images identified hyporeflective spaces as a red area that was automatically calculated by particle analysis function and included for the statistical analysis. The area (mm2) of the cystoid cavities in the INL and OPL+ HFL with both en face and OCTA were considered for statistical analyses. The data were analyzed by GraphPad PRISM Software (Version 6.0; GraphPad, La Jolla, CA). The association between the total cavity areas between groups was evaluated with the Pearson coefficient correlation for the area within the INL and, the area within the OPL + HNL complex. The area within each layer for each group was also analyzed for an association to macular hole diameter. P values less than .05 were considered statistically significant.

Results

The mean age of the study sample was 59.2 years ± 3.7 years. The mean baseline BCVA was 26.8 ETDRS letters ± 9.7 letters. Figure 2 presents OCTA of a healthy eye and an eye with FTMH. The INL contains small, circular hyporeflective spaces surrounding the FTMH, and the OPL + HFL complex contains elongated radial hyporeflective cavities arranged in a stellate pattern (Figure 2).


Optical coherence tomography angiography of a healthy eye and an eye with macular hole. The retinal vascular differences between the healthy and pathologic eye correspond mainly to the deep network of vessels. Small, circular, hyporeflective spaces are present surrounding the macular hole in the inner nuclear layer, whereas elongated radial hyporeflective cavities forming a stellar pattern are observed in the outer plexiform/Henle fiber layers complex.

Figure 2.

Optical coherence tomography angiography of a healthy eye and an eye with macular hole. The retinal vascular differences between the healthy and pathologic eye correspond mainly to the deep network of vessels. Small, circular, hyporeflective spaces are present surrounding the macular hole in the inner nuclear layer, whereas elongated radial hyporeflective cavities forming a stellar pattern are observed in the outer plexiform/Henle fiber layers complex.

In all eyes, the cystoid cavities were small and rounded in the INL and were an elongated, stellate pattern in the OPL+HFL. The cystoid cavities had better definition within the INL using en face imaging compared to OCTA. The appearance of the cystoid cavities was very similar within the OPL + HFL complex between groups (Figure 3).


An eye with full-thickness macular hole eye analyzed with 1) optical coherence tomography angiography of the deep retinal vascular network; 2) en face scan of the outer nuclear layer slab. The sliding of the deep retinal vascular network has an overlapped representation in the enface scan in the same segmentation of the slab corresponding to the outer plexiform and Henle fiber layers.

Figure 3.

An eye with full-thickness macular hole eye analyzed with 1) optical coherence tomography angiography of the deep retinal vascular network; 2) en face scan of the outer nuclear layer slab. The sliding of the deep retinal vascular network has an overlapped representation in the enface scan in the same segmentation of the slab corresponding to the outer plexiform and Henle fiber layers.

Table 1 presents the clinical characteristics, patient demographics, and the area of the cystoid cavities in both groups. The mean axial length was 23.31 mm ± 0.69 mm. There were four eyes with stage 3 FTMH and nine eyes with stage 4 FTMH. The mean macular hole diameter was 567.06 µm ± 153.66 µm. There were nine eyes with macular adhesion or traction. Using en face images, the total cavity area in the INL and OPL + HFL was 0.86 mm2 ± 0.46 mm2 and 1.65 mm2 ± 0.88 mm2, respectively. With OCTA images, the total cavity area in INL and OPL + HFL was 0.95 mm2 ± 0.47 mm2 and 1.66 mm2 ± 0.87 mm2, respectively.

Figure 4 presents the outcomes of automated identification of the hyporeflective spaces in the INL and in the OPL + HFL complex with en face and OCTA images. The cystoid cavities were identified by the Image J algorithm.


Automated identification of hyporeflective spaces in the inner nuclear layer (INL) and in the complex formed by the outer plexiform layer (OPL) and Henle fiber layer (HFL) on en face scan and optical coherence tomography angiography (OCTA). (Top row) OCT B-scan displaying the outline of the plane of the en face section (Blue: INL; Red: OPL + HFL). (Second row) En face OCT showing the distinct patterns of hyporeflective spaces in the INL and the complex of the OPL and HFL. (Third row) Automated detection of the cavity area from the en face images (in red) by Image J software. (Fourth row) OCTA showing the distinct patterns of hyporeflective spaces in the INL and the complex of the OPL and HFL. (Last row) Automated detection of the cavity area from the OCTA images (in red) by Image J software.

Figure 4.

Automated identification of hyporeflective spaces in the inner nuclear layer (INL) and in the complex formed by the outer plexiform layer (OPL) and Henle fiber layer (HFL) on en face scan and optical coherence tomography angiography (OCTA). (Top row) OCT B-scan displaying the outline of the plane of the en face section (Blue: INL; Red: OPL + HFL). (Second row) En face OCT showing the distinct patterns of hyporeflective spaces in the INL and the complex of the OPL and HFL. (Third row) Automated detection of the cavity area from the en face images (in red) by Image J software. (Fourth row) OCTA showing the distinct patterns of hyporeflective spaces in the INL and the complex of the OPL and HFL. (Last row) Automated detection of the cavity area from the OCTA images (in red) by Image J software.

There was a statistically significant positive correlation in the area of the cystoid cavities within the INL between groups (P < .001; r2 = 0.82) (Figure 5). There was a statistically significant positive correlation in the area of the cystoid cavities within the OPL + HFL complex between groups (P < .001; r2= 0.84) (Figure 6).


Scatterplot of the statistically significant positive correlation (P < .001; r2= 0.82) between optical coherence angiography and enface scan of the automated cavity area calculation by the Image J algorithm for the inner nuclear layer.

Figure 5.

Scatterplot of the statistically significant positive correlation (P < .001; r2= 0.82) between optical coherence angiography and enface scan of the automated cavity area calculation by the Image J algorithm for the inner nuclear layer.


Scatterplot of the statistically significant positive correlation (P < .001; r2= 0.84) between optical coherence angiography and en face scan of the automated cavity area calculation by the Image J algorithm for the outer plexiform layer and Henle fiber layer complex.

Figure 6.

Scatterplot of the statistically significant positive correlation (P < .001; r2= 0.84) between optical coherence angiography and en face scan of the automated cavity area calculation by the Image J algorithm for the outer plexiform layer and Henle fiber layer complex.

There was no correlation between the macular hole diameter and the total intraretinal area of the cystoid cavity for the en face group (P = .71; r2= 0.12). The macular hole diameter and the total intraretinal area of the cystoid cavity for the OCTA group were not correlated (P = 0.49; r2= 0.04) (Figure 7). There was also no correlation between cystoid cavities in the INL or the OPL + HFL complex and macular adhesion or traction (P > .01).


Overlapped scatterplots indicating no statistically significant correlation (P = .71 and r2= 0.12; P= .49 and r2= 0.04), respectively, of the enface cavity area and optical coherence tomography angiography in the total area of the inner nuclear layer, outer plexiform layer, and Henle fiber layer complex correlated to hole dimension.

Figure 7.

Overlapped scatterplots indicating no statistically significant correlation (P = .71 and r2= 0.12; P= .49 and r2= 0.04), respectively, of the enface cavity area and optical coherence tomography angiography in the total area of the inner nuclear layer, outer plexiform layer, and Henle fiber layer complex correlated to hole dimension.

Discussion

This comparison of en face and OCTA images for perifoveal cystoid cavities associated to FTMH found statistically significant correlations between the imaging modalities. For example, the cavity areas in the INL were statistically correlated between groups. Similar outcomes were found for cystoid cavities in the OPL+HFL complex in the current study. Matet et al.4 reported that en face OCT of a macular hole has a unique presentation in the INL and the OPL+HFL complex. Evaluating only en face images, they4 described small, somewhat spherical hyporeflective cystoid spaces in the INL surrounding the macular hole and elongated radial cavities forming a stellate pattern in the OPL+HFL complex. Our outcomes from both en face and OCTA imaging concur with Matet et al. observations.4 To our knowledge, this is the first comparison of en face and OCTA for cystoid cavities associated to FTMH in English peer-reviewed literature (search terms in Google, Google Scholar, PubMed, and SCOPUS: en face, ocular optical coherence tomography, OCT, OCTA, OCTA, ophthalmic optical coherence tomography angiography, cystoid cavities, cystoid spaces). Additionally, this is the first comparison of these imaging modalities with the RS 3000 Advance tomographer. The outcomes in the current study are consistent with outcomes from tomographers used in Matet et al. study.4

The intraretinal distribution of cystoid cavities presented in the current study is related to the distribution of Müller cells.4,15 The unique Z-shape course of the Müller cells within the retinal layers is responsible for the structural changes that cause cystoid cavities.16

We observed comparable structural alterations in OCTA analysis in the superficial and deep vascular network. For example, the mean cavity areas in superficial and deep vascular networks were statistically significantly correlated between OCTA and en face images. This observation implies that the retina surrounding the cystoid spaces preserves circulation as shown by OCTA. The overlap of images observed in en face and OCTA indicates that OCTA can detect the flow between one cystoid space and another. The residual flow suggests nonischemic tissue and “vascular sliding” at the border of the cavities. This phenomenon can generate changes to the vascular structure causing retinal tissue damage. Future analysis is warranted to assess the long-term effects changes in retinal vasculature after vitreoretinal surgery. Additionally, it would be interesting to determine whether the morphological changes can influence the choice and the timing of surgery.

Although several hypotheses have been postulated, the pathogenesis of FTMH remains unknown. Studies have proposed anterior-posterior vitreomacular traction and posterior vitreous detachment as potentiating factors with the vitreomacular interface playing a fundamental role in development of FTMH.4,17 In the current study, nine eyes had macular adhesion or traction (Table 1). Although we found no statistically significant correlations between cystoid spaces in the INL or OPL + HFL and macular adhesion or traction, severe anterior-posterior retinal traction can generate significant intraretinal fluid.18 Notably, we found the diameter of the macular hole was not correlated to the cystoid cavities in OCTA although a positive trend can be observed (Figure 7). This outcome concurs with the International Vitreomacular Traction Study Group that reported intraretinal cystic spaces are not related to the stage of the macular hole.19

In this study, we compared OCTA to en face OCT scans to characterize and quantify the retinal vasculature “sliding” around the cystoid spaces associate to FTMH. This phenomenon can result in abnormal vascular structure and consequently functional retinal damage. A very interesting finding has been recently reported by Romano et al., who described a significant correlation between the inner area of the epiretinal traction and BCVA. Probably the retinal stress induced by epiretinal traction can be implicated as prognostic factor in ERM result.20 In addition, the presence of excessive fluid in the intercellular spaces or within the cells can result in dysfunctional regulation of Müller cells that may remain altered after resolution of the FTMH.

This study has some limitations, including a limited number of eyes and the lack of documentation of the changes of pathologic features over time. However, we have shown that perifoveal cystoid cavities can be detected by OCTA. Additionally, analyzing OCTA and en face images from the same tomographer allowed us to reduced variability involved with using multiple units.

In conclusion, OCTA of the foveal region in FTMH was well-correlated with en face OCT scans due to the distribution of the Müller cells in the macula. Additional details, such as the absence of vascular flow due to the intraretinal cystoid cavities, are visible in OCTA. OCTA analysis in FMTH and the assessment of vascular involvement should be an important tool to identify changes in microcirculation after vitreoretinal surgery.

Additional multicenter studies enrolling larger sample sizes, with different OCTA devices are warranted to verify the preliminary findings reported here.

References

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Authors

From the Department of Neural-Skeletal-Muscles and Sensory Organs Diseases, Eye Clinic, Careggi University, Florence, Italy (SR, AS, DB); and Catholic University, “A. Gemelli” Foundation, Rome (MCS).

The authors report no relevant financial disclosures.

The authors thank Bruno Lumbroso for his pioneering work in optical coherence tomography angiography and his thoughtful teachings. This research was not supported by any grant or other economical funds.

Address correspondence to Maria Cristina Savastano MD, PhD, Catholic University. Largo “A. Gemelli,” 00198 Rome, Italy; email: mariacristina.savastano@gmail.com

Received: August 11, 2016
Accepted: November 29, 2016

10.3928/23258160-20161219-09

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