Imaging of naive myopic choroidal neovascularization by spectral-domain optical coherence tomography.

Original Paper

Ophthalmologica

Ophthalmologica 2014;232:28–36 DOI: 10.1159/000357980

Received: November 6, 2013 Accepted after revision: December 10, 2013 Published online: April 16, 2014

Imaging of Naive Myopic Choroidal Neovascularization by Spectral-Domain Optical Coherence Tomography Paolo Milani a Alfredo Pece b Luisa Pierro c Fulvio Bergamini a a

Istituto Auxologico Italiano, b Fondazione Retina 3000, and c Ospedale San Raffaele, Milan, Italy

Key Words Myopia · Pathologic myopia · Optical coherence tomography · Spectral-domain optical coherence tomography · Choroidal neovascularization · Myopic choroidal neovascularization

ly hyperreflective, causes thickening of the corresponding retina and mainly involves the external retinal segments. Retinal fluid is infrequent. © 2014 S. Karger AG, Basel

Abstract Purpose: To assess the tomographic features of myopic choroidal neovascularization by spectral-domain optical coherence tomography. Methods: We consecutively reviewed the charts of patients with pathologic myopia, recent visual acuity deterioration and active macular neovascularization. Specific tomographic changes were studied in 25 eyes by two authors independently. Results: The mean age of patients eligible for the study was 63.4 (±18.2) years. Main tomographic outcomes were the hyperreflectivity of the lesion in 88% of cases (95% CI 0.74–1.02), absence of the external limiting membrane in 88% (95% CI 0.84–1.02), and retinal thickening in 83% (95% CI 0.67–0.99). The internal plexiform layer remained discernible in 83% (95% CI 0.67–0.99) of cases, the inner nuclear layer in 62% (95% CI 0.37–0.80), the external plexiform layer in 48% (95% CI 0.27–0.69). Retinal edema was noted in 48% (95% CI 0.26–0.70) of patients. Conclusions: Myopic choroidal neovascularization appears predominant-

© 2014 S. Karger AG, Basel 0030–3755/14/2321–0028$39.50/0 E-Mail [email protected] www.karger.com/oph

Optical coherence tomography (OCT) is widely used for the diagnosis and study of vitreoretinal pathologies, and retinal details can now be defined better with spectral-domain (SD) technology [1]. Pathologic myopia, characterized by high myopic refraction (more than –6 diopters), areas of chorioretinal atrophy, chorioretinal thinning and staphyloma, is frequently complicated by myopic choroidal neovascularization (mCNV) [2], which has its own particular patterns and reportedly responds well to intravitreal anti-VEGF agents [3, 4]. The tomographic aspects of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) have been amply described [5, 6], but mCNV has been studied less by SD-OCT, although these forms are among the main causes of vision loss in developed countries, estimated to occur in 5–10% of patients with high myopia [7–10]. Paolo Milani Via Stefini 10 IT–20125 Milan (Italy) E-Mail dottpaolomilani @ hotmail.com

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Introduction

Materials and Methods We retrospectively reviewed the charts of patients who presented consecutively in our institution between April 2011 and April 2012. Inclusion criteria were: refractive error more than –6 diopters, visual acuity deterioration and metamorphopsia dating back less than 1 month, FA documentation of macular CNV, tomographic evidence of retinal profile changes in correspondence to the lesion. The multimodal imaging system that combines scanning laser ophthalmoscopy angiography, IR reflectance and SD-OCT (‘Spectralis’, Heidelberg Engineering, Germany) was used in all cases. Up to 40,000 A scans/s can be taken, and an axial digital resolution of 3.9 μm in tissue and transversal digital resolution of up to 15 μm (high-resolution mode) are possible with a superluminescence diode at 870 nm central wavelength. We considered only eyes with: (1) documentation of initial (0–45 s), middle (1–2 min) and late (more than 4 min) phases of the lesion hyperfluorescence after injection of 2.5 ml of fluorescein; (2) volume scans of the entire macular area and with additional horizontal and vertical linear scans positioned by the examiner in the center of the lesion as assessed by FA and OCT. The software provided has an ‘automatic realtime’ function to reduce noise and improve image quality. In our clinic every examiner follows usually a standard protocol of acquisition: with automatic real-time activated, macular volume scans averaged at 9 multiple frames (B scan) are taken along with linear scans averaged at 100 frames positioned manually by the operator over the mCNV. IR imaging of the CNV was then identified with the function that matches the lesion by the pointer provided by the software. The predominant appearance (white or black) was recorded. Areas of macular chorioretinal atrophy were identified at autofluorescence. Exclusion criteria were: cataract that made fundus visualization impossible; images of bad quality; signs of AMD such as drusen; generally, patients with pathologies of the vitreomacular interface such as macular hole, glaucoma, optic nerve inflammation or patients who did not meet the above-mentioned criteria. Similarly, cases were excluded that were treated by intravitreal therapies, photodynamic therapy or vitreoretinal surgery. FA experts (P.M., A.P.) examined the angiographic findings, noting the characteristics of the mCNV. Since it is often hard to identify the limits of the anatomic fovea in pathologic myopia, the mCNV was considered foveal-juxtafoveal if positioned 1–199 μm from the center of the typical area of foveal depression as shown by the OCT scan, or extrafoveal if positioned at 200 or more micrometers. Focal or diffuse area(s) of choriocapillary-retinal pigment epithelium (RPE) atrophy in the macula were noted, as well as the contiguity of the lesion to an atrophic area. mCNV extension was measured by Spectralis software that circumscribes the lesion, then calculates the area in square millimeters. The boundaries were identified by one of the authors assessing the lesion in the early phase of FA, and then overlaid with the mouse. The size was also assessed clinically, considering a CNV as ‘big’ only when the diam-

SD-OCT Details of mCNV

eter of the lesion was larger than a maximum papillary diameter, as ‘small’ if smaller. Specific tomographic changes were then studied indipendently by 2 retinal experts (P.M., L.P.) with broad experience in OCT. They peculiarly examined the aspect of the neovascular complex as assessable by every volume and linear scan conducted inside the lesion. Using a grading scale (yes/no/doubtful) they had to establish the presence or absence of the following inside the lesion: Bruch’s membrane, RPE layer band persistence, RPE layer focal interruption, RPE detachment, inner-outer segment (IS/OS) junction (adjacent and inside the lesion), external limiting membrane (ELM), outer and inner nuclear layers (ONL, INL), internal and external plexiform layers, retinal edema, hyperreflectivity of the lesion at SD-OCT, retinal thickening (i.e. increased retinal thickness in correspondence to the lesion), hyperreflective dots, epiretinal membrane, shadowing effect towards the choroid. Hyperreflectivity (yes/no/doubtful) was defined when the signal of the OCT appeared whitish in the tomograms. In figure 1, there is an example of the adopted grading system. Retinal edema was defined as spaces (possibly cysts) that presented at OCT with no or low reflectivity inside the retinal profile. Statistical Analysis Statistical analyses were carried out using SAS 9.2. software. After an initial estimate of the mean behavior of each variable, correlations between each pair were analyzed by the two-tailed Pearson test. General linear model (GLM) and multivariate multiple regression analysis were then done to check correlations and linear relations among variables.

Results

Twenty-five eyes of 25 patients were eligible for the study; 15 were women, 10 men. Mean age (±SD) was 63.4 (±18.2) years, 95% confidence interval 55–70. Mean spherical equivalent was –10.24 diopters. Out of the 13 pseudophakic patients the preoperating refractive error was considered for analysis. Table 1 summarizes the patients’ main demographic details and their FA and OCT findings. Most of the mCNV were in the foveal-juxtafoveal area (92%), small (80%), and not close to an area of atrophy (68%). The average mCNV area was 0.84 ± 0.63 mm2, with a maximum of 2.1 mm2. Three eyes had two distinct but contiguous areas of leakage, suggesting a multishaped mCNV. The 2 examiners agreed fully on the FA features, and the level of disagreement on the interpretation of the SDOCT findings was 3.08%, with a 95% confidence interval of 1.20–4.96%. Thus the 2 examiners completely agreed on the OCT interpretation in more than 95% of cases. Table 2 presents the means, standard deviation and 95% confidence interval for the variables considered. Besides the impossibility of identifying Bruch’s membrane and the IS/OS junction in all the cases, the main tomoOphthalmologica 2014;232:28–36 DOI: 10.1159/000357980

29


This study provides a morphological description of the tomographic appearance of mCNV assessed by SD-OCT. Scanning laser ophthalmoscopy-fluorescein angiography (FA) and infrared (IR) findings were also investigated.

Color version available online

Fig. 1. Patient 6, left eye. IR imaging (a),

a

c

graphic finding was the hyperreflectivity of the CNV in 88%, absence of the ELM in 88%, and retinal thickening in 83% of patients. The ONL and the external plexiform layer were unrecognizable in 79 and 52% of cases, respectively, but the INL and the internal plexiform layer remained discernible inside the lesion complex in 62 and 83%. A shadowing effect was definitely noted in 86% of patients, but the investigators had some doubt about it in 12%. Twelve patients (48%) presented hyperreflective dots and 10 (40%) had epiretinal membrane (fig. 1, 2). Table 3 shows the variables which were significantly correlated (p < 0.05). The strongest linear correlations were between shadowing effect and ONL absence (ρ 0.84, p < 0.0001), ELM absence (ρ 0.61, p < 0.01) and retinal thickening (ρ 0.53, p < 0.01). Areas measured by the software and clinically by the examiner were strongly directly correlated (ρ 0.86, p < 0.0001) and the lesions appeared larger when near an atrophic area (ρ 0.73, p < 0.0001). The area of the lesion tended to increase with age (ρ 0.42, p < 0.05) but only slightly. 30

b


Higher correlations (between two sets of measures) are not shown since none were significant. The only significant multiple relation was between the area and either the dimension of the mCNV and age (GLM, p < 0.001, R2 = 0.79) or the dimension of the mCNV and IR appearance (GLM, p < 0.001, R2 = 0.85).

Discussion

The morphology of mCNV has still not been amply studied by OCT. Baba et al. [11] used time-domain OCT to investigate the morphologic changes in 11 eyes with active mCNV and detected a highly reflective, dome-like elevation above the RPE, without subretinal fluid. Using more recent SD techniques, Introini et al. [12] proved mCNV to appear as a hyperreflective lesion with fuzzy borders and a more highly reflective core above the RPE, associated with thickening of the overlying retina in 95.5% of the eyes investigated. However, it must be taken Milani /Pece /Pierro /Bergamini


late-phase angiography with SD-OCT scanning (b) and SD-OCT details of the lesion (c). (Colors refer to the online version only.) The red arrow shows the position of the mCNV that appears mainly white in the IR images with a black halo (a) and presents leakage at angiography (b) where the thin green arrow indicates the position of the scan. In c the mCNV appears like a dome-shaped elevation of the RPE in the center of the image (red arrow). The following layers are indicated adjacent to the lesion: ELM (*), ONL (△), external plexiform layer (§), INL (○), internal plexiform layer (#). Only the last feature was considered recognizable by both the examiners in the portion of the retina involved by the lesion. The mCNV caused thickening of the corresponding retina and hyperreflectivity. Some hyperreflective dots are also recognizable (white arrow) as well as a shadowing effect toward the choroid (black arrow).

M 81 M 79

M F F F

Patient

3 4 5 6

Age

M M F M F F

F M F F

F M F F F M F

9 10 11 12 13 14

15 16 17 18

19 20 21 22 23 24 25


Eye

Re Le Re Re Le Le Le

Le Re Re Le

Le Le Le Le Re Le

Re Re

Re Le Le Le

Le Re

Spherical equivalent

–9 –12 –10 –18 –7 –8 pseudo –8

–7 pseudo –8 pseudo –16 pseudo –12 pseudo

–12 –6 pseudo –9 pseudo –9 pseudo –13 pseudo –7 pseudo

–14 –9

–12 pseudo –18 –7 pseudo –10

–6 –9 pseudo

Foveal-juxtafoveal Y Y Y Y Y Y Y

Y Y Y Y

N Y Y Y N Y

Y Y

Y Y Y Y

Y Y

Macular chorioretinal atrophy Y Y Y N N N N

N N Y N

N N Y Y Y N

Y N

Y N N N

N N

Near atrophic area Y Y N N N N N

N Y N N

N N Y N Y N

Y N

Y N N N

N Y

white white, black halo black white white white, black halo white black, white halo white white white white IND white, black halo white black black white and black IND black black IND white white white and black S S S S S, 2 branches S S

S B S S

S, tapered S, tapered B, 2 branches S S S

B S, tapered

B S S S

S B

Area 0.2 1.27 0.67 0.15 0.61 0.6 0.43

0.37 2.18 0.94 1.07

0.19 0.14 1.62 0.4 0.29 0.43

1.92 1.18

1.68 0.43 0.72 0.88

0.53 2.15

Persistent IS/OS junction-BM presence N N N N N N N

N N N N

N N N N N N

N N

N N N N

N N

Persistent RPE layer N Y Y Y Y N Y

N Y Y Y

Y Y Y D Y Y

N N

N Y Y Y

D Y

Adjacent persistent IS/ OS junction N N N Y Y Y Y

Y N Y Y

Y Y N Y N N

N N

N Y N N

Y Y

RPE detachment N N N N N N N

N N N N

N N N N N N

N N

N N N N

N N

RPE focal interruption Y Y N N N Y N

Y N N Y

N Y N Y Y N

Y Y

Y N N YN

Y N

Persistent ELM N N N N N N N

N Y N N

N Y N N N N

N N

N N Y N

N N

Retinal fluid N N Y N Y Y N

YN Y N Y

N YN Y Y N Y

N Y

N N N N

Y Y

Persistent ONL N N Y N N N N

N N YN N

N Y N N N N

N N

Y N Y N

N Y

Persistent EXT plexiform Y N Y N N N N

N Y Y Y

Y Y N N Y N

N Y

N N Y N

Y Y

Persistent INL Y YN Y, cysts N Y Y Y

N Y Y Y, cysts

Y Y N N Y N

N Y

N N Y N

Y, cysts Y, cysts

Persistent INT plexiform Y YN Y Y Y Y N

Y Y Y Y

Y Y N N Y Y

Y Y

Y N Y Y

Y Y

Lesion hyperreflectivity Y Y D Y Y Y Y

Y Y D Y

D Y Y Y Y Y

Y Y

Y Y Y Y

Y Y

Retinal thickening Y Y Y YN Y N Y

Y Y Y Y

Y N Y N Y Y

Y Y

Y Y N Y

Y Y

Hyperreflective dots N Y N N Y N N

Y Y N Y

N Y Y N Y Y

N N

N N N Y

Y Y

Y Y N Y

N Y N Y N Y N

N Y Y N

N N N Y N Y

Y Y D Y D Y Y

Y Y D Y

Y N Y Y Y YN

Y Y Y Y

N Y N N

N Y N Y

ERM Shadow

31


RE = Right eye; LE = left eye; Y = yes; N = no; YN = disagreement between the examiners; D = doubtful; IND=indeterminable; S = small, i.e. diameter of the lesion smaller than a papillary diameter; B = big, i.e. diameter of the lesion larger than a papillary diameter; BM = Bruch’s membrane; ext. = external; int. = internal; ERM = epiretinal membrane.

44 66 54 20 40 81 75

63 76 85 88

43 44 71 45 82 82

F 52 M 68

7 8

80 45 52 71

Sex

1 2

IR appearance

Table 1. Demographics of the patients, with FA and OCT features

CNV dimension

SD-OCT Details of mCNV

Table 2. Means and standard deviations of the variables examined, with the lower and upper limits of the 95%

confidence interval (CI) in the last two columns Variable

Mean

Standard deviation

Lower limit mean 95% CI

Upper limit mean 95% CI

Age Foveal/juxtafoveal Macular chorioretinal atrophy IR appearance (white) Near an atrophic area CNV small (lesion smaller than a papillary diameter) Area (measured by software), mm2 Persistent RPE layer RPE focal interruption Persistent ELM Edema Persistent ONL Persistent external plexiform layer Persistent INL Persistent internal plexiform layer Lesion hyperreflectivity Retinal thickening Hyperreflective dots Epiretinal membrane Shadow

63.48 0.92 0.36 0.70 0.32 0.80 0.84 0.74 0.50 0.12 0.48 0.17 0.48 0.62 0.83 0.88 0.83 0.48 0.40 0.86

18.22 0.28 0.49 0.47 0.48 0.40 0.63 0.45 0.51 0.33 0.51 0.38 0.51 0.50 0.38 0.33 0.38 0.51 0.50 0.35

55.96 0.81 0.16 0.48 0.12 0.63 0.58 0.54 0.28 –0.02 0.26 0.01 0.27 0.37 0.67 0.74 0.67 0.27 0.19 0.71

71.00 1.03 0.56 0.92 0.52 0.97 1.10 0.93 0.72 0.26 0.70 0.33 0.69 0.80 0.99 1.02 0.99 0.69 0.61 1.00

Most of the mCNV cases studied are foveal-juxtafoveal (92%), and besides the impossibility of identifying Bruch’s membrane and the IS/OS junction in all the patients, the main tomographic finding is the hyperreflectivity of the mCNV in 88%, absence of the ELM in 88%, and retinal thickening in 83% of cases. A shadowing effect is definitely noted in 86% of patients. The external retinal layers such as the ONL and the external plexiform appear more involved by the lesion complex than the internal retina.

Table 3. Pairs of significant (95%) variables with Pearson’s correlation coefficient ρ and the corresponding p values

Variable 1

Variable 2

Area Shadow Near an atrophic area Persistent INL Focal interruption Near an atrophic area Shadow Near an atrophic area Shadow Retinal thickening Persistent ONL Persistent int. plexiform layer Area

CNV small persistent ONL CNV small persistent ext. plexiform layer persistent RPE layer area persistent ELM macular chorioretinal atrophy retinal thickening persistent ELM persistent ELM persistent ext. plexiform layer age

ρ

p value

–0.86 –0.84 –0.73 0.68 –0.67 0.64 –0.61 0.55 0.53 –0.51 0.51 0.45 0.42

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