High-Resolution Imaging of the Photoreceptor Layer in Epiretinal Membrane Using Adaptive Optics Scanning Laser Ophthalmoscopy

doi:10.1016/j.ophtha.2010.08.032

Ophthalmology

Volume 118, Issue 5, May 2011, Pages 873-881

Presented at: the 2009 Joint Meeting of the American Academy of Ophthalmology and Pan-American Association of Ophthalmology (PO605), October 2009, San Francisco, California.

https://doi.org/10.1016/j.ophtha.2010.08.032 Get rights and content

Objective

To compare, in eyes with an idiopathic epiretinal membrane (ERM), photoreceptor cell structural abnormalities identified on high-resolution images obtained by adaptive optics scanning laser ophthalmoscopy (AO-SLO) with the severity of metamorphopsia and anatomic findings on spectral-domain optical coherence tomography (SD-OCT).

Design

Observational case series.

Participants

Twenty-five eyes of 24 patients with idiopathic ERM and 20 normal eyes of 20 volunteer subjects.

Methods

All participants underwent a full ophthalmologic examination, SD-OCT, and imaging with an original prototype AO-SLO system that incorporated liquid crystal-on-silicon technology. In eyes with ERM, M-CHARTS results were used to quantify metamorphopsia.

Main Outcome Measures

Cone mosaic patterns on AO-SLO images and metamorphopsia severity.

Results

In normal eyes, AO-SLO images showed a regular photoreceptor mosaic pattern. In 24 (96%) of 25 eyes with ERM, “microfolds” (multiple thin, straight, hyporeflective lines in the photoreceptor layer) were identified on AO-SLO images; microfolds were not seen in normal eyes. Individual microfolds were approximately 5 to 20 μm wide, which is narrower than retinal folds seen in fundus photographs (>50 μm). Amsler charts revealed metamorphopsia around the fixation point in 12 of 13 eyes with microfolds in the fovea on AO-SLO but in none of 5 eyes without microfolds in the fovea (P < 0.001). Compared with eyes without foveal microfolds, eyes with foveal microfolds had more severe metamorphopsia (M-CHARTS distortion) in both horizontal and vertical lines (P < 0.001 for both) and greater average foveal thickness detected by SD-OCT (P=0.010). Voronoi analysis revealed that smaller numbers of cones in eyes with ERM had 6 neighbors, compared with normal eyes (P < 0.001). In eyes with ERM, average foveal thickness measured by SD-OCT correlated with visual acuity (P=0.001) and metamorphopsia scores, both horizontal (P=0.002) and vertical (P < 0.001), but visual acuity, metamorphopsia scores, and average foveal thickness were not related to SD-OCT findings of disruption in the photoreceptor inner and outer segment junction.

Conclusions

Adaptive optics scanning laser ophthalmoscopy images in eyes with ERM showed abnormal cone mosaic patterns, described as microfolds in the foveal photoreceptor layer. The presence of microfolds was associated with metamorphopsia, suggesting that microfolds may be involved in the formation of metamorphopsia.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Materials and Methods

All investigations adhered to the tenets of the Declaration of Helsinki, and the study was approved by the institutional review board and the ethics committee at Kyoto University Graduate School of Medicine. The nature of the study and its possible consequences were explained to study candidates, after which written informed consent was obtained from all who participated.

Results

On AO-SLO images in 24 (96%) of the 25 eyes with ERM, many thin, straight hyporeflective lines in the cone mosaic were observed (Figs 2 and 3 [available at http://aaojournal.org]; Fig 4). These lines, which we describe as “microfolds,” were not seen in any normal eyes (Fig 1).

The microfolds appeared in localized clusters, with the microfolds in each cluster aligned almost in parallel. Each microfold was approximately 5 to 20 μm wide, which was narrower than the 50-μm or wider retinal folds seen

Discussion

Although vision changes due to metamorphopsia are a major symptom in patients with ERM, the structural abnormalities that underlie the vision disturbance remain unknown. A previous study using binocular correspondence perimetry⁸ attributed the vision changes to retinal or photoreceptor displacement, whereas other studies suggested that vision changes could be due to clinical findings, such as folds of the internal limiting membrane or the ERM, displacement of vessels toward the fovea, abnormal

Acknowledgments

The authors thank the imaging specialists of Kyoto University OCT Reading Center (Mayumi Yoshida and Akiko Hirata) for evaluating AO-SLO images.

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To investigate cellular-level morphological alterations in the retinal neuroglia in eyes with epiretinal membrane (ERM).
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We included 41 eyes with unilateral idiopathic ERM and 33 healthy eyes of healthy volunteers.
We examined the foveal microstructures in all eyes using adaptive optics OCT (AO-OCT) with axial and lateral resolutions of 3.4 and 3.0 μm, respectively. Adaptive optics OCT images were acquired for a 2.5° (728 μm) area at the foveal center.
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Adaptive optics OCT imaging of healthy eyes and eyes with ERM revealed sharp hyperreflective lines of the external limiting membrane (ELM), accompanied by hyporeflective gaps, individual nuclei of the foveal cone photoreceptors, and Müller cell bodies. The arrangement of Müller cell bodies was more vertical in eyes with ERM than in normal eyes. Epiretinal membranes adhered to foveal Müller cells via the internal limiting membrane (ILM), exerting vertical traction that pulled the foveal cones anteriorly. Adaptive optics OCT also enabled visualization of outer segment (OS) discs. Hyperreflective changes in the OS discs were observed beneath the vertically thickened ellipsoid zone (EZ) in 15 eyes (36.6%) with ERM. For eyes with ERM, multiple regression analysis showed that the length from ILM to the inner border of the outer nuclear layer and the EZ thickness were significantly associated with BCVA (β = 5.3 × 10^-4 and 82.7 × 10^-4, respectively), with associated 95% confidence intervals of 1.3 × 10^-4 to 9.3 × 10^-4 (P = 0.011) and 39.0 × 10^-4 to 126.5 × 10^-4 (P < 0.001), respectively. The EZ thickness was significantly and positively associated with the length from ELM to the retinal pigment epithelium (β = 23.9 × 10^-2, 95% confidence interval: 4.8 × 10^-2 to 42.9 × 10^-2; P = 0.015).
Cellular imaging of retinal neuroglia by AO-OCT may suggest possible mechanisms associated with visual impairment in patients with ERM, which could potentially contribute to the growing body of knowledge on its pathophysiology. However, these insights require further validation through extensive studies to fully ascertain their significance.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Tractional deformations of the fovea mainly arise from an anomalous posterior vitreous detachment and contraction of epiretinal membranes, and also occur in eyes with cystoid macular edema or high myopia. Traction to the fovea may cause partial- and full-thickness macular defects. Partial-thickness defects are foveal pseudocysts, macular pseudoholes, and tractional, degenerative, and outer lamellar holes. The morphology of the foveal defects can be partly explained by the shape of Müller cells and the location of tissue layer interfaces of low mechanical stability. Because Müller cells and astrocytes provide the structural scaffold of the fovea, they are active players in mediating tractional alterations of the fovea, in protecting the fovea from such alterations, and in the regeneration of the foveal structure. Tractional and degenerative lamellar holes are characterized by a disruption of the Müller cell cone in the foveola. After detachment or disruption of the cone, Müller cells of the foveal walls support the structural stability of the foveal center. After tractional elevation of the inner layers of the foveal walls, possibly resulting in foveoschisis, Müller cells transmit tractional forces from the inner to the outer retina leading to central photoreceptor layer defects and a detachment of the neuroretina from the retinal pigment epithelium. This mechanism plays a role in the widening of outer lameller and full-thickness macular holes, and contributes to visual impairment in eyes with macular disorders caused by conractile epiretinal membranes. Müller cells of the foveal walls may seal holes in the outer fovea and mediate the regeneration of the fovea after closure of full-thickness holes. The latter is mediated by the formation of temporary glial scars whereas persistent glial scars impede regular foveal regeneration. Further research is required to improve our understanding of the roles of glial cells in the pathogenesis and healing of tractional macular disorders.
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Many eyes with macular pucker are characterized by a centripetal displacement of the inner foveal layers which may result in a disappearance of the foveal pit. In this retrospective case series of 90 eyes with macular pucker of 90 patients, we describe using spectral-domain optical coherence tomography different foveal configurations with ectopic inner foveal layers, document the relationship between posterior vitreous detachment (PVD) and idiopathic epiretinal membrane (ERM) formation and spontaneous and postoperative morphological alterations of the fovea, and propose an active role of Müller cells in the development of foveal herniation. We found that ERM were formed during or after partial perifoveal PVD, or after foveal deformations caused by tissue edema. The ERM-mediated centripetal displacement of the inner foveal layers and in various eyes anterior hyaloidal traction caused a disappearance of the foveal pit and an anterior stretching of the foveola with a thickening of the central outer nuclear layer (ONL). After the edges of the thickened inner layers of the foveal walls moved together, continuous centripetal displacement of the inner foveal layers generated a bulge of the fovea towards the vitreous (foveal herniation). Macular pseudoholes with a herniation of the inner foveal layers show that the outer layer of the protruding foveal walls is the outer plexiform layer (OPL). If the ERM covered the foveal walls and parafova, but not the foveola, the inner layers of the foveal walls were not fully centripetally displaced and the foveal pit was present. The visual acuity of eyes with ectopic inner foveal layers was inversely correlated with the thickness of the foveal center. Spontaneous morphological alterations after disappearance of the foveal pit may include the development of cystoid macular edema or additional thickening of the foveal tissue and foveal herniation. The foveal configuration with ectopic inner layers of the foveal walls and a thick central ONL persisted over longer postoperative time periods. The data show that the centripetal displacement of the inner foveal layers in eyes with macular pucker, which results in a disappearance of the foveal pit, may also generate foveal herniation which is suggested to be caused by contraction of Müller cell processes in the OPL. The centripetal displacement of the inner foveal layers and the formation of foveal herniation are suggested to reverse the foveal pit formation during development.
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: Manuscript no. 2010-124.

: Financial Disclosure(s): The author(s) have made the following disclosure(s): Masanori Hangai and Nagahisa Yoshimura are paid members of the advisory boards of Topcon and NIDEK. Susumu Oshima is an employee of NIDEK. Takashi Inoue is an employee of Hamamatsu Photonics.

: Supported in part by the New Energy and Industrial Technology Development Organization (NEDO; P05002), Kawasaki, Japan.

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Original articleHigh-Resolution Imaging of the Photoreceptor Layer in Epiretinal Membrane Using Adaptive Optics Scanning Laser Ophthalmoscopy

Objective

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Financial Disclosure(s)

Section snippets

Materials and Methods

Results

Discussion

Acknowledgments

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Quantification of metamorphopsia in patients with epiretinal membranes

Invest Ophthalmol Vis Sci

Retinal contraction and metamorphopsia scores in eyes with idiopathic epiretinal membrane

Invest Ophthalmol Vis Sci

Function and morphology of macula before and after removal of idiopathic epiretinal membrane

Invest Ophthalmol Vis Sci

Objective signs of photoreceptor displacement by binocular correspondence perimetry: a study of epiretinal membranes

Invest Ophthalmol Vis Sci

Morphologically functional correlations of macular pathology connected with epiretinal membrane formation in spectral optical coherence tomography (SOCT)

Graefes Arch Clin Exp Ophthalmol

Correlation of visual recovery with presence of photoreceptor inner/outer segment junction in optical coherence images after epiretinal membrane surgery

Br J Ophthalmol

Correlation between thickening of the inner and outer retina and visual acuity in patients with epiretinal membrane

Retina

Associations between macular findings by optical coherence tomography and visual outcomes after epiretinal membrane removal

Am J Ophthalmol

Supernormal vision and high-resolution retinal imaging through adaptive optics

J Opt Soc Am A Opt Image Sci Vis

The arrangement of the three cone classes in the living human eye

Nature

Original article
High-Resolution Imaging of the Photoreceptor Layer in Epiretinal Membrane Using Adaptive Optics Scanning Laser Ophthalmoscopy