Understanding Pathologic Myopia

Fundus complications due to pathologic myopia are a major cause of visual impairment and blindness worldwide, especially in East Asian countries. The patients with pathologic myopia develop loss of the best-corrected vision due to various lesions occurring in the macula and the optic nerve. In the META-PM (meta analyses of pathologic myopia) study classification, pathologic myopia has been defined by the presence of myopic chorioretinal atrophy equal to or more serious than diffuse atrophy and/or the presence of posterior staphyloma. In addition, the advent of new imaging technologies, such as optical coherence tomography (OCT), ultra wide-field OCT, and three-dimensional magnetic resonance imaging (3D MRI) has enabled the detailed observation of various pathologies specific to pathologic myopia. In addition, new pathology such as dome-shaped macula has been clarified. Therapeutic approaches such as intravitreal injections of anti-vascular endothelial growth factor agents and the vitreoretinal surgeries for myopic macular retinoschisis have greatly improved the prognosis of patients with pathologic myopia. In the future, therapies targeting staphylomas are expected.


Introduction
Pathologic myopia (PM) is a major cause of blindness in the world, especially in East Asian countries [1][2][3][4][5]. The cause of blindness in patients with PM includes myopic maculopathy with or without posterior staphyloma, myopic macular retinoschisis, and glaucoma or glaucoma-like optic neuropathy. In this chapter, the lesions of myopic fundus complications including posterior staphylomas are described.

Definition of Pathologic Myopia
The terms "pathologic myopia," "high myopia," and "axial myopia" have long been used in a parallel manner in the literature. According to recent discussions, the term "high myopia" simply describes the status of a "high degree of myopia" and should be defined by a cut-off value of myopic refractive error. The term "axial myopia" may be used to describe the situation with an axial elongation as cause for the myopic refractive error. It is in contrast to the term refractive myopia, which is used for eyes with an abnormally high refractive power of their optical media. The term "pathologic myopia" describes the situation of pathologic consequences of a myopic axial elongation. According to a recent consensus article by Ohno-Matsui et al. [6], pathologic myopia was defined by myopic chorioretinal atrophy equal to or more serious than diffuse atrophy (by META-PM study group classification [7]) and/or the presence of posterior staphylomas.

Posterior Staphyloma
Posterior staphyloma has been considered a hallmark lesion of pathologic myopia. While axial elongation may primarily start in the equatorial and retro-equatorial region with secondary changes taking place at the posterior fundus, posterior staphylomas occur in the posterior segment of the eye and can be associated with, or lead to, vision-threatening complications in the macula as part of a myopic maculopathy [7][8][9][10][11] and myopic optic neuropathy/glaucoma [12,13]. (Fig. 9.

1)
A posterior staphyloma is an outpouching of a circumscribed area of the posterior fundus, where the radius of curvature is less than the curvature radius of the surrounding eye wall [14].

Detection of Posterior Staphyloma
Moriyama et al. recently applied three-dimensional magnetic resonance imaging (3D-MRI) to analyze the shape of the entire eye from the corneal surface to the posterior pole including even large posterior staphylomas ( Fig. 9.2) [15][16][17]. The technique allowed visualizing a staphyloma from any angle. The advantage of 3D-MRI of visualizing the shape of the whole eye including the anterior ocular segment is combined with its disadvantage of not being feasible as a screening technique. Instead, a new prototype of a wide-field swept-source optical coherence tomographic (OCT) system has been developed, which uses not only one but multiple scan lines and which generates scan maps allowing a three-dimensional reconstruction of posterior staphylomas in a region of interest of 23 × 20 mm with a depth of 5 mm. Applying a wide-field OCT (WF-OCT), Shinohara et al. [18] showed that WF-OCT could provide tomographic images of posterior staphylomas in a resolution and size unachievable up to that time, and that WF-OCT might replace 3D-MRI in examining posterior staphylomas. Upon WF-OCT, the edges of the staphylomas showed consistent features, consisting of a gradual thinning of the choroid from the periphery toward the staphyloma edge and a gradual rethickening of the choroid from the staphyloma edge in direction to the posterior pole ( Fig. 9.3). An additional advantage of the swept-source WF-OCT technology was the relatively large depth of focus so that structures from the posterior vitreous to the sclera could be imaged in the same image. It allowed the analysis of relationships between vitreoretinal abnormalities and other lesions in the inner retinal layers, such as myopic macular retinoschisis and posterior staphylomas as reported by Shinohara et al. [19] (Fig. 9.4). Fig. 9.

3)
Based upon and modifying Curtin's [20] classical categorization of posterior staphylomas, with Types I-V as primary staphylomas and Types VI-X as compound staphylomas, Ohno-Matsui [17] used 3D-MRI and wide-field fundus  imaging to reclassify staphylomas into six types: the wide macular type, the narrow macular type, the peripapillary type, the nasal type, the inferior type, and others ( Fig. 9.5). Table 9.1)

Myopic Chorioretinal Atrophy (META-PM Study,
In the META-PM classification [7], myopic maculopathy lesions have been categorized into five categories from "no myopic retinal lesions" (Category 0), "tessellated fundus only" (Category 1; Fig. 9.6a), "diffuse chorioretinal atrophy" (Category 2; Fig. 9.6b), "patchy chorioretinal atrophy" (Category 3; Fig. 9.6c), to "macular atrophy" (Category 4; Fig. 9.6d). These categories were defined based on long-term clinical observations that showed the progression patterns and associated factors of the development of myopic choroidal neovascularization (CNV) for each stage. Three additional features were added to these categories and were included as "plus signs": (1) lacquer cracks ( Fig. 9.6e) and (2) myopic CNV ( Fig. 9.6f) ( Table 9.1). Since a Fuchs' spot represented a scarred form of myopic CNV, Fuchs' spots were categorized under the term of myopic CNV. The reason for separately listing the "plus signs" was that all three lesions have been shown to be strongly associated with central vision loss; however, they did not fit into any particular category and might develop from, or coexist, in eyes with any wide, macular Type I  T ype II  Type III  Type IV  Type V inferior O thers narrow, macular peripapillary nasal Fig. 9.5 Classification staphyloma (cited from [17] with permission). New classification of posterior staphyloma according to its location and extent. The staphyloma type is renamed according to its location and distribution. Type I → wide, macular staphyloma, Type II → narrow, macular staphyloma, Type III → peripapillary staphyloma, Type IV → nasal staphyloma, Type V → inferior staphyloma, others → staphylomas other than Types I-V  of the myopic maculopathy categories described above. Based on this classification, pathologic myopia has now been defined as myopic maculopathy Category 2 or above, or the presence of "plus" sign or posterior staphyloma [7,21].

Diffuse Chorioretinal Atrophy (Category 2)
Diffuse chorioretinal atrophy is characterized by a yellowish white appearance of the posterior pole. The region of the diffuse atrophy may extend from a restricted area around the optic disc and a part of the macula to the entire posterior pole. The atrophy generally first appears around the optic disc, often increases with age, and finally covers the entire area within a staphyloma if a staphyloma is present. Both older age and longer axial length have been described as risk factors for the development of diffuse atrophy [9]. Marked thinning of the choroidal layer in the area of diffuse atrophy can be detected upon OCT, with occasional large choroidal vessels remaining.

Patchy Chorioretinal Atrophy (Category 3)
Patchy chorioretinal atrophy appears as well-defined, grayish white lesion(s) in the macular area or around the optic disc. Upon OCT, the area of patchy atrophy is characterized by the absence of the entire choroid and the RPE as well as of the outer retina. Hyper-transmission through the underlying sclera can be seen upon OCT. Using swept-source OCT, Ohno-Matsui et al. [22] showed that patchy atrophy was not simply a chorioretinal atrophy but was combined with a defect in Bruch's membrane (BM).

Lacquer Cracks (Plus Sign)
Lacquer cracks appear as yellowish linear lesions in the macula. Lacquer cracks have been considered to represent breaks in BM [9,[23][24][25]. Progression patterns of lacquer cracks include an increased number, elongation, and progression to patchy atrophy [8,26]. Detection of lacquer cracks can sometimes be difficult especially in eyes with diffuse atrophy. Assessments of hyper-fluorescence by fluorescein angiography and hypo-fluorescence upon indocyanine green angiography have been useful for the diagnosis. Other linear lesions due to pathologic myopia with a similar hypofluorescence upon by indocyanine green angiography, such as myopic stretch lines, have to be differentiated [27].
Due to their small width, linear defects in BM as the base of lacquer cracks are difficult to be directly detected. Instead, hyper-reflective lines of the choroidal and scleral tissue layers on the OCT images indirectly indicate the linear BM defect by an optical window effect ( Fig. 9.7). The recently developed imaging technique of OCT angiography may be useful for detecting a rupture of the choriocapillaris in the area of lacquer cracks, again indirectly indicating a defect in BM [28]. Since a subretinal bleeding can often be observed at the onset of the development of lacquer cracks [29][30][31] (Fig. 9.8), it is important to exclude the presence of a myopic CNV in cases of subretinal bleeding in the region of lacquer cracks.

Myopic CNV and CNV-Related Macular Atrophy
Myopic CNV is a major sight threatening complication of pathologic myopia. It is the most common cause of CNV in individuals younger than 50 years, and it is the second most common cause of CNV overall [25,32]. Myopic CNV is a Type II CNV and shows a clear hyper-fluorescence by fluorescein angiography. Anti-VEGF therapy is the first-line treatment for myopic CNV, as shown by the RADIANCE study [33] and the MYRROR study [34]. In the long-term, both in treated eyes and in eyes exposed to the natural course of the disorder, macular atrophy develops around the scarred CNV and impairs central vision ( Fig. 9.9). Swept-source OCT showed that CNV-related macular atrophy was not simply a chorioretinal atrophy but was BM hole [35], like patchy chorioretinal atrophy.
As shown upon OCT-angiography, the CNV maintains its blood flow even when the CNV transforms into the scar phase, including the area of CNV-related macular atrophy (Fig. 9.10). Louzada et al. [36] and Giuffre et al. [37] reported that blood vessels originating from the sclera were found at the site of myopic CNVs. Recently Ishida et al. [38] reported that the blood vessels of myopic CNVs were continuous to scleral branches of short posterior ciliary arteries ( Fig. 9.11).

Myopic Macular Retinoschisis
Using optical coherence tomography, Takano and Kishi first demonstrated a foveal retinal detachment and retinoschisis in severely myopic eyes with posterior staphylomas [39]. Panozzo and Mercanti proposed the term "myopic traction maculopathy (MTM)" to encompass various findings characterized by a traction as visualized by OCT in highly myopic eyes [40]. Myopic traction maculopathy, also called foveal retinoschisis [39], macular retinoschisis [41], or myopic foveoschisis [42], includes the features of schisis-like inner retinal fluid, schisis-like outer retina fluid, foveal detachment, lamellar or full-thickness macular hole, and/or macular detachment [43]. These features can best be detected by OCT as an indispensable tool to diagnose MTM. Additional examination techniques are a retro-mode imaging which uses an infrared laser in the confocal scanning laser ophthalmoscope and which can produce a pseudo-three-dimensional image showing the details of deep retinal structures ( Fig. 9.12). Applying retro-mode imaging, a characteristic fingerprint and firework pattern at the corresponding area of a macular retinoschisis have been detected in the region of a macula retinoschisis [44,45]. Shimada et al. have classified myopic traction maculopathy according to its location and extent from S0 through S4: S0: no retinoschisis; S1: extrafoveal; S2: foveal; S3: both foveal and extrafoveal but not the entire macula; and S4: entire macula [46].

Dome-Shaped Macula (DSM)
A dome-shaped macula (DSM) is an inward protrusion of the macula as visualized by OCT ( Fig. 9.13) [47][48][49]. Imamura et al. reported that a DSM was associated with, and caused by, a local thickening of the subfoveal sclera [50]. It was postulated that the local thickening of the subfoveal sclera was an adaptive or g h The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.