Optical coherence tomography and pathological myopia

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Aug 10, 2015 - progression. OCT and .... mation, or asymmetry in staphyloma progression have .... microfolds and intraretinal cyst or lamellar holes [27,. 28].

Int Ophthalmol DOI 10.1007/s10792-015-0118-y


Optical coherence tomography and pathological myopia: an update of the literature Maria Vittoria Cicinelli . Luisa Pierro . Marco Gagliardi . Francesco Bandello

Received: 23 April 2015 / Accepted: 10 August 2015  Springer Science+Business Media Dordrecht 2015

Abstract The purpose of this paper is to give an updated review of the last clinical entities in pathological myopia proposed by means of new generation optical coherence tomography (OCT), including enhanced depth imaging (EDI-OCT) and swept source OCT (SS-OCT). PubMed and Google engine search were carried out using the terms ‘‘pathological myopia’’ associated with ‘‘coherence tomography,’’ ‘‘enhanced depth imaging,’’ and ‘‘swept source OCT.’’ Latest publications up to Jan 2015 about myopiarelated complications, including open-angle chronic glaucoma, peripapillary retinal changes, acquired macular diseases, and choroidal neovascularization, have been reviewed. New OCT technologies have led to a greater insight in pathophysiology of high-grade myopia. However, further investigation is needed in order to prevent irreversible visual loss and optic nerve damage.

Pathological myopia (PM) is defined as a refractive error greater than 6 D or an axial length greater than 26.5 mm. PM is one of the major causes of legal blindness in developed countries, as its complication, including myopic macular degeneration, choroidal neovascularization (CNV), retinal detachment, and chronic open-angle glaucoma, may irreversibly threaten visual acuity. Thanks to the development of new optical coherence tomography (OCT) technologies, such as enhanced depth imaging (EDI-OCT) and swept source (SS-OCT), deeper insights in PM pathogenesis have been achieved. Nowadays, OCT has become fundamental in the diagnosis and management of PMrelated complications. The purpose of this paper is to give an updated review of new clinical entities in PM proposed by means of OCT.

Keywords Pathologic myopia  Optical coherence tomography  Myopic CNV  Dome-shaped macula  Myopic macular hole

Myopia and glaucoma

M. V. Cicinelli (&)  L. Pierro  M. Gagliardi  F. Bandello Department of Ophthalmology, San Raffaele Scientific Institute, Vita-Salute University, Via Olgettina, 60, 20132 Milan, Italy e-mail: [email protected]

PM and glaucoma have been demonstrated to be significantly associated [1], even though optic disk changes in PM, such as greater peripapillary atrophy (PPA), secondary acquired macrodisk, deeper excavation, and reduced neural rim, lead to high rate of false positive in the diagnosis of glaucoma. Moreover, retinal nerve fiber layer (RNFL), whose reduction supports diagnosis of glaucoma, may be thinner in highly myopic patients [2] and its accurate segmentation on OCT may be affected by tilted insertion of the disk.


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A recent OCT study has correlated the horizontal insertion angle of the optic disk with the refractive error (r = -1.53 per each diopter), and the vertical angle with the risk to develop glaucoma (r = 6.56) (P \ 0.001) [3]. PPA can be divided into three regions: alpha zone, the most peripheral; beta zone, characterized by retinal pigment epithelium (RPE) and scleral atrophy, but conserved Bruch membrane; and gamma zone, the innermost, where also Bruch membrane disappears. Beta zone is positively related to glaucomatous damage but not to axial length; gamma zone, on the contrary, is related to axial length but not to neuronal damage [4]; therefore, OCT helps in beta zone recognition and in indirect assessment of glaucoma progression.

OCT and peripapillary area Histomorphological analyses of peripapillary area in highly myopic eyes showed three elements recognizable: the scleral flange, between the optic nerve margin and dura mater; the dura mater, on the external border of the scleral flange; and an enlarged subarachnoid space (SAS) between the dura and the pia mater [5]. Ohno-Matsui et al. identified SAS on SS-OCT in 124 of 133 myopic eyes (93 %), appearing as a hyporeflective triangle containing weakly hyperreflective arachnoid trabeculae, with the base toward the eye and the apex toward the optic nerve [6]. Expanded SAS means an expanded area of optic nerve exposed to cerebrospinal pressure, and this, along with thinning of the posterior eye wall that increases the pressure load on the peripapillary sclera, may potentially increase susceptibility to glaucoma and visual field (VF) defects in these patients. In fact, VF defects, defined as a decrease of C10 % of the outermost V4 isopter, not explained by retinal lesion on ophthalmoscopy, are not uncommon in highly myopic eyes [7] and morphofunctional OCT studies have been addressed to peripapillary area in order to justify these functional defects. For example, 71 % of myopic eyes with peripapillary intrachoroidal cavitation (ICC) showed glaucomatous VF defects. ICC, formerly defined as ‘‘peripapillary detachment of pathologic myopia’’ [8], is a yellow–orange elevated lesion inferior to optic nerve, corresponding


on OCT to hyporeflective cavity under the RPE (Fig. 1). Sometimes, a triangular thickening near the border of the optic nerve is recognizable and has been interpreted as residual of tissue of Jacoby. The prevalence of ICC in PM is around 4.9 and 9.4 %; in one patient, it was associated with a macular neuroretinal detachment. Pathophysiology of ICC is not clear, but it is thought to be the result of destruction of tissue connecting the choroid and the lamina cribrosa, known as tissue of Elschnig, secondary to staphyloma progression. However, using EDI-OCT and SS-OCT, Spaide and Ohno-Matsui hypothesized that in eyes with full-thickness retinal defects over the lesion, where a direct connection between vitreous and choroid is established, ICC is the result of vitreal fluid dissection [9]. OCT helps in distinguishing between ICC and acquired optic nerve and myopic conus pits; acquired pits prevalence in a SS-OCT study was 32 (11 optic pit and 22 conus pit) on 198 eyes (16.2 %) [10]. Optic pits are triangle-shaped nerve fiber invagination (up to [1000 l) in the superior or inferior border of the optic disk. Their pathogenesis is connected to optic disk enlargement: stretching forces break the connections between lamina cribrosa and scleral flange, particularly at the superior and inferior poles, causing an interruption and herniation of nerve fibers over these defects. In fact, they are generally associated with higher refractive error and axial length and with larger optic disk (7.2 ± 2.1 mm2) and conus areas. Conus pits are less frequent than optic nerve pits, are found mostly in type IX staphyloma as per Curtin, and involve nerve fibers, neuroretina, and choroid in the myopic conus (Fig. 2). They often correspond to entrance point of short posterior ciliary arteries through the sclera, where its wall is weaker; in certain cases, indeed, a scleral schisis can be recognizable under the pit.

OCT and CNV PM is the first cause of macular CNV in patients younger than 50 years old [11], and myopic CNV are one of the first causes of irreversible visual loss in myopic patients. Its prevalence is 10–15 % but about 15–20 % of patients with CNV in one eye will develop a CNV in the fellow one. However, visual prognosis and post-treatment outcome is generally better than

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Fig. 1 a Color figure of an intrachoroidal cavitation (ICC) in the inferior part of the myopic conus. b Optical coherence tomography of the peripapillary region shows a hyporeflective cavity under the retinal pigment epithelium (star)

Fig. 2 Fundus image (a) and optical coherence tomography scan (b) of an acquired myopic conus pit

other types of CNV, especially those of age-related maculopathy (ARM). Chorioretinal atrophy at the posterior pole and lacquer cracks are considered risk factors for CNV development [12]. Gold standard for diagnosis is fluorescein angiography (FA); some authors have reported a poor correlation between FA and OCT at baseline and during follow-up of these lesions [13]. Leveziel et al. have reported that active CNV was associated with exudative features on FA in 82 % of cases, and on SDOCT in only 48.6 % of cases. Moreover, among the eyes affected, diagnosis of CNV was made by FA alone in 60 % of cases, by OCT alone in 28.9 % of cases, and by both OCT and FA in 11.1 % of cases [14]. OCT remains a helpful tool in differential diagnosis in case of macular hemorrhage between CNV and lacquer cracks, and in case of subretinal fluid between CNV and dome-shaped macula (DSM).

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) have shown promising results, and are currently considered the first-line therapy for subfoveal and juxtafoveal myopic CNV. Clinical history of myopic CNV is divided into three phases: active, scar, and atrophy. Introini et al. have demonstrated that active CNV is associated with a hyperreflective lesion with fuzzy borders above the RPE (type 2 CNV), ‘absent or altered’ IS/OS junction on SD-OCT, and minimal subretinal or intraretinal exudation [15]. On the contrary, disappearance of fuzzy area and thickening of the RPE after intravitreal treatment suggests a shifting toward the phase of scar. In the atrophic phase, CNV fibrosis becomes flat and surrounded by an area of choriocapillary atrophy; patients have higher risk to develop macular hole (14 %) on the edge of fibrosis.


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OCT and DSM Diagnosis of DSM has been first reported by Gaucher and associates [16]. DSM is a forward macular bulging within the posterior staphyloma in highly myopic eyes and its prevalence is estimated to be 10.7 % by an European study and 9.3 % by a Japanese study. Caillaux and associates classified DSM into 3 subtypes using EDI-OCT: the horizontally oriented oval-shaped dome (62.5 %), the vertically oriented oval-shaped dome (16.7 %), and the round dome (20.8 %), equal on both axis of the staphyloma [17]. DSM is often associated with serous retinal detachment (SRD), and whose symptoms are similar to those of CNV, including central scotoma and metamorphopsia: differential diagnosis between these two entities may be challenging. The exact pathophysiology of DSM is still unclear: local choroidal and scleral thickening, ocular hypotony, tangential vitreomacular traction, resistance to staphylomatous deformation, or asymmetry in staphyloma progression have been proposed. Since areas of thickened sclera have been found, the term ‘‘scleral compression maculopathy’’ has been proposed instead of DSM, because of compressive changes on the choroid and choriocapillaris and resultant secondary subretinal fluid collection and atrophic RPE damages [18, 19]. There is no agreement on the treatment of DSM-associated serous detachment: Tamura et al. reported a case of bilateral DSM healed with no therapy [20]; encouraging results come from anti-mineralocorticoid receptor inhibitors and half-dose PDT. Argon laser photocoagulation and anti-VEGF intravitreal injection have been not effective strategies.

OCT and vitreomacular disorders Early vitreous degeneration is an important risk factor for posterior vitreous detachment (PVD), vitreomacular traction, foveoschisis, epiretinal membrane (ERM), and lamellar macular holes. Therefore, study of the vitreous by means of OCT has become of primary interest. Thanks to SS-OCT, the first in vivo visualization of the posterior precortical vitreous pocket (PPVP) has been achieved [21]. PPVP is a boat-shaped lacunae in the macular area that had been described before only on postmortem preparations or during vitreo-retinal surgery after triamcinolone


staining. Its formation is connected to vitreal liquefaction: OCT showed that complete myopic PVD is often preceded by partial PVD starting at the PPVP site. Moreover, in cases of PVD, OCT identifies vitreal cortex remnants on retinal surface that seem to play a primary role in premacular idiopathic fibrosis and myopic macular hole formation [22, 23]. Full thickness myopic macular holes (MMH) are found in 6–7 % of highly myopic patients, and their prevalence is positively correlated with refractive error [24]. The pathogenesis of myopic MH is poorly understood, unlike idiopathic or post-traumatic MMH; vitreous anterior–posterior traction, oblique or tangential traction by posterior hyaloid, ERM, internal limiting membrane or retinal vessels, posterior outward traction from the staphyloma are possible mechanisms involved in MH formation. Myopic foveoschisis (MF) is believed to be one of the main causes of MMH formation in highly myopic eyes. The term MF was introduced in 1999 by Takano and Kishi to describe the splitting of the inner macular layers, usually at the outer plexiform layer, in highgrade posterior staphyloma. Its prevalence ranges from 9 to 34 % and it is more common in Asian and in women between 50 and 60 years old. On OCT, MF appears as a collection of intraretinal cyst separating the retina into a thinner outer layer and a thicker inner layer, with hyperreflective bridging columns. Moreover, OCT is essential for early recognition, prevention, and treatment of MF-associated complications: 76 % of MF is associated with internal limiting membrane detachment, MMH or macular hole retinal detachment (MHRD), spontaneously or after vitrectomy, that make the surgical retinal reattachment more difficult and worsen the post-treatment visual prognosis. The evolution from MF to MMH was classified into two OCT patterns, according to where the first retinal defect develops [25]. Pattern 1 starts with an OLMH and a small retinal detachment in the outer retina, that becomes a MMH when the roof of the OLMH opens in the vitreous. Pattern 2 starts with a foveal pseudocyst in the inner retina; the cyst progresses splitting posteriorly until it reaches RPE. Progression time toward a complete MMH is 11 and 9 months, respectively. Recently, Lin et al. has described four different pathways of MMH formation, other than MH from MF, based on OCT macular feature [26]:

Int Ophthalmol Fig. 3 Four different pathways of myopic macular hole (MMH) formation, before (left) and after (right) MMH development. a Type 1: normal foveal depression with abnormal vitreo-retinal traction; b Type 2: macular schisis without macular detachment; c Type 3: macular schisis with concomitant or subsequent macular detachment; d Type 4: macular atrophy with underlying or adjacent submacular CNV scar

• •

Type 1: Normal foveal depression with an abnormal vitreo-retinal relationship (vitreo-foveal traction or tangential premacular traction from ERM). Type 2: Macular schisis without macular detachment; all these cases are preceded by a lamellar macular hole. Type 3: Macular schisis with concomitant or subsequent macular detachment. Type 4: Macular atrophy with underlying or adjacent submacular CNV scar (Fig. 3).

Success rate in MMH repairing surgery is lower than that of non-myopic macular holes (60 % of closure cases versus 90 %) with MMH associated with foveal detachment of neuroepithelium having worse prognosis that lesion without detachment.

like changes rather than cystoid spaces or lamellar holes. Shimada et al. reported that patients with paravascular cyst have higher myopic error, longer axial length, and more severe grade of staphyloma compared to patients without cysts. PIRD are often accompanied by a functional abnormality on VF. Detection of PIRD, and in particular of paravascular lamellar holes, seems to be a risk factor for macular foveoschisis; it has been postulated that glial cells, as astrocytes, that are abundant in the paravascular area, migrate through retinal solution and proliferate over its surface, leading to collagen deposition and ILM thickening. Increased thickness and rigidity of ILM impairs retinal stretching following staphyloma progression and causes an antero-posterior retinal traction important in MF pathogenesis.

Paravascular inner retinal defect OCT is a very useful tool not only in the diagnosis of peripapillary or macular pathologies (MF, MHRD, and MMH), but also of more peripheral lesions. Paravascular inner retinal defects (PIRD) are spindleshaped or caterpillar-shaped dark retinal defects along the major retinal vessels. PIRD include paravascular microfolds and intraretinal cyst or lamellar holes [27, 28]. On transverse OCT sections, they appear as cystoid or fissure-like spaces; however, longitudinal OCT sections along the major retinal vessels reveal that most PIRDs were actually broader retinoschisis-

Conclusions New OCT technologies have led to greater insight in pathophysiology of high-grade myopia and its complications that can cause severe and irreversible reduction of visual acuity. Treatment of these complications, including antiVEGF intravitreal injection and surgery, has dramatically changed visual prognosis of myopic patients; however, further investigation is needed in order to prevent staphyloma progression and optic nerve damage.


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Compliance with ethical standards Conflict of interest The authors have no conflict of interest in the materials used in this study.

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