Prof. (Dr.) Atul Kumar
Chief, Dr RP Centre for
Ophthalmic Sciences, AIIMS,
New Delhi
Dr. Srikant Padhy
Senior Resident, Vitreous – Retina Services
Dr RP Centre for Ophthalmic Sciences,
aiims, new delhi
Dr. Twinkle Parekh
Junior Resident, Vitreous – Retina Services
Dr RP Centre for Ophthalmic Sciences,
AIIMS, New Delhi
Introduction
Myopia is the most common refractive error affecting significant proportion of population. The incidence of myopia is constantly on rise. High myopia is defined as a refractive error with spherical equivalent more than –6 dioptres (D) and/or the axial length longer than 26.5 mm.1,2 Pathological myopia (PM) or degenerative myopia denotes to axial myopia with characteristic pathological changes at the posterior pole.
Complications from pathological myopia are the major causes of blindness and visual impairment. Visual loss in pathological myopia can be attributed by pathologies in either macula or peripheral retina or optic disc or in combination. Early recognition of such pathologies can prevent socioeconomic burden of the disease by timely intervention. In last two decades, the new-fangled modalities of investigation like ocular coherence tomography (OCT), OCT angiography (OCTA), widefield imaging, fundus autofluorescence (FAF) imaging has enhanced the early recognition of these pathologies. More so these modern technologies help the ophthalmologist in understanding of the disease process and progression. Novel treatment technologies such as anti-angiogenesis therapy and small gauge vitrectomy have also boosted the treatment outcomes of some complications associated with high myopia. This article will throw light on our current understanding of the various macular complications in high myopia as well as current modalities in managing these conditions.
Myopic Maculopathy
Curtin and Karlin in 1970 first proposed a definition of myopic maculopathy which included the features of chorioretinal atrophy, central pigment spot, lacquer cracks, posterior staphyloma and optic disc changes.3 Later, Tokororestructured the classification into four categories:
(1) Tessellated Fundus
(2) Diffuse Chorioretinal Atrophy
(3) Patchy Chorioretinal Atrophy
(4) Macular Hemorrhage
Afterwards, Avila et al.designed a classification which classified myopic retinopathy according to severity,from “M0-
normal-appearing posterior pole; M1: – choroidal pallor and tessellation; M2: – M1 + posterior staphyloma; M3: – M2 + lacquer cracks; M4: – M3 + focal areas of deep choroidal atrophy; to the most severe grade M5: – M4 + large geographic areas of deep chorioretinal atrophy and bare sclera”.4 Regardless of the efforts from Curtin and Avila,
the definition of myopic maculopathy has not been unswerving across studies.
META-PM study
Of late an international panel of researchers proposed a simplified, uniform classification system for pathologic myopia.5 In this simplified system (META-PM classification), myopic maculopathy lesions are categorized into 5 categories from “no myopic retinal lesions” (Category 0), “tessellated fundus only” (Category 1), “diffuse chorioretinal atrophy” (Category 2), “patchy chorioretinal atrophy” (category 3), to “macular atrophy” (Category 4). These categories were defined on the basis of long-term clinical observations on the progression patterns and risk of
myopic CNV development for each stage. Three additional features were added to these categories and were designated as “plus signs”: (1) lacquer cracks, (2) myopic CNV, and (3) Fuchs spot. The motive for separately defining these “plus signs” is that these 3 lesions have been shown to be strongly associated with central vision loss, but they do not fit into any particular category and may develop from, or coexist, in eyes with any of the myopic maculopathy categories described above. Based on this new classification, pathologic myopia is defined as myopic maculopathy category 2 or above, or presence of “plus” sign, or the presence of posterior staphyloma. It is anticipated that future clinical trials and epidemiological studies will espouse this uniform classification to facilitate communication and comparison of findings.
Macular Chorioretinal Atrophy
Chorioretinal atrophy occurs due to progressive thinning of the choroid, disappearance of choroidal vessels, and loss of RPE and photoreceptors.6 The cause behind atrophy is probably choroidal vascular occlusion and abiotrophic degeneration. Chorioretinal atrophy is of two types diffuse atrophy and patchy atrophy
Diffuse chorioretinal atrophy
(category 2) is yellowish white in appearance, mostly located in the posterior pole. Its extent may diverge from a small restricted area around the optic disc and a part of the macula to the entire posterior pole. It generally first appears around the disc, often increasing with age and lastly covering the whole area within the staphyloma. On FFA, it displays mild hyperfluorescence in the late phase due to tissue staining where as a marked decrease of the choroidal capillary and medium and large-sized choroidal vessels is reported on ICGA. OCT revealsmarked thinning of the choroidal layer in the area of diffuse atrophy.7
Patchy Chorioretinal atrophy
(Category 3) appears as well-defined, greyish white lesion(s) in the macular area or around the optic disc. Patchy chorioretinal atrophy is characterized by a complete loss of choriocapillaris and can progress to an absence of outer retina and retinal pigment epithelium. Large choroidal vessels can be seen to course within the area of patchy atrophy. In advanced cases, the posterior fundus shows a “bare sclera” appearance. Pigment clumping is observed generally along the margin of the atrophy or along the large choroidal vessels. The lesion appears hypofluorescent on FA and ICGA due to choroidal filling defect. The overlying RPE is lost, leading to hypoautofluorescence usually with
distinct borders. On OCT, the area of patchy atrophy is characterized by absence of the entire thickness of the choroid and the RPE as well as outer retina. Hyper-transmission through the underlying sclera can be seen. The frequencies of chorioretinal atrophy progression and the risk of CNV development are significantly higher in eyes with patchy chorioretinal atrophy, compared to those with diffuse chorioretinal atrophy. Macular retinoschisis and retinal detachment secondary to posterior paravascular linear retinal breaks have been reported to occur preferably in areas of patchy atrophy. It is possible that adhesion between the inner retina and sclera in these areas are weakened.
Lacquer cracks (Plus sign)
Lacquer cracks appear as yellowish linear lesions in the macula. These are believed to epitomizemechanical breaks of the Bruch’s membrane. They may appear as linear horizontal or vertical cracks or exhibit a crisscrossing (stellate) pattern. Its frequency in patients with pathologic myopia fall between 4.3 and 15.7%. Generally, lacquer cracks develop at a relatively early age.9 However, the frequency increases with age. Detection of lacquer cracks with conventional examination methods is tough. ICGA is considered as the best method for detecting lacquer cracks, which characteristically appear as linear hypofluorescence in the late phase.10 FA, on the other hand, is less useful in demonstrating lacquer cracks, particularly during the early stages of rupture. The reason is thought to be due to leakage from the surrounding normal choriocapillaris, which may obscure it, and the lack of atrophy of the overlying retinal pigment epithelium during the early stages of lacquer crack formation. FAF imaging appear as linear hypo-autofluorescence. OCT shows discontinuities of the RPE and increased hyper-transmission into the deeper tissue beyond the RPE. However, detection rate is low because the lesions are often very narrow and hardly visible on OCT. Reduction in macular choroidal thickness is also noted on OCT. A study reported that a subfoveal choroidal thickness cut-off value of 58.93μm may be useful for screening eyes for the presence of lacquer cracks. OCTA demonstrates tracks with lack of a decorrelation signal at the level of choriocapillaris due to disruption of flow.
Subretinal bleeding is frequently observed at the onset of lacquer cracks. This subretinal bleeding is usually absorbed spontaneously with good visual recovery and has therefore been called simple hemorrhage. However, in eyes in which the bleeding was thick and penetrated into the inner retina beyond the external limiting membrane, a defect in the ellipsoid zone may persist, leaving permanent vision loss. It is important to exclude the presence of a myopic CNV in cases of subretinal bleeding. Progression of lacquer cracks is reported to be more frequent in eyes with posterior staphyloma. This may appear as elongation from the tip of an existing lacquer crack, at the side of an existing lacquer crack in a branching pattern, or remote from an existing lacquer crack and connecting later in a bridging pattern. Lacquer crack is one of the important risk factors in the formation of myopic CNV.1
Förster Fuchs’ Spot
These are raised, pigmented, round, or elliptical dark colored lesion but can have various colors likegray, yellow, red, or green hue. It is nothing but proliferation of RPE associated with choroidal hemorrhage
Figure 1: Myopic CNVM seen on SS-OCT, FFA, OCTA.
Myopic CNV (Plus sign)
Myopic CNV is the most common sight threatening complication of pathologic myopia.13 It is the commonest cause of CNV in individuals aged below 50 years, and the second commonest cause of CNV overall. “Plus” sign has been assigned to it in the proposed international classification for myopic maculopathy, in view of its major bearing on vision. Myopic CNV develops in 10% of high myopes and 30% myopes eventually develop CNV in the other eye as well.7 The risk factors for development of myopic CNV includes focal chorioretinal atrophy, steeper posterior staphyloma, and lacquer cracks. The natural history of myopic CNV is generally poor without treatment.14 Development of chorioretinal atrophy around the regressed CNV is the main reason for the poor visual prognosis in eyes with myopic CNV. Suspicion of myopic CNV should arise when a patient of high myopia develops sudden onset metamorphopsia and central scotoma.
On clinical examination, myopic CNV typically appears as a flat, small, greyish subretinal lesion beneath or in close proximity to the fovea with or without hemorrhage. The diagnosis of myopic CNV can be established by FA and OCT. FA in myopic CNV exhibits well-defined hyperfluorescence in the early phase with leakage in the late phase in a classic CNV pattern of leakage. OCT has the benefit of being non-invasive and fast to perform. Therefore,OCT is routinely employed to differentiate myopic CNV from other macular conditions in high myopia such as myopic foveoschisis and myopic macular hole, and for monitoring of the myopic CNV treatment response.15 In our clinical practice, we prefer to do both FA and OCT while planning for management of such cases. Active myopic CNV in OCT appears as a dome-shaped hyperreflective elevation above the RPE as most myopic CNV are type 2 CNV. Subretinal hyperreflective exudation on OCT has also been proposed to be a feature of active myopic CNV. Other OCT features of myopic CNV include absence of Bruch’s membrane and photoreceptor ellipsoid zone, absence of external limiting membrane (ELM) and retinal thickening. A recent study evaluated the correspondence of FA and SD-OCT findings in myopic CNV eyes receiving intravitreal bevacizumab treatment and found that absence of ELM was a more reliable parameter for assessing myopic CNV than intra- or sub-retinal fluid.16 With the use of enhanceddepth imaging OCT, patients with myopic CNV have been found to have thinner choroidal thickness compared with normal control eyes. Other imaging techniques which might provide adjunctive information in the assessment of myopic CNV include ICGA and FAF. ICGA is particularly useful in the assessment of lacquer crack formation associated with myopic CNV. FAF findings in myopic CNV may include hyperautofluorescent or patchy FAF pattern, and eyes with hyperautofluorescent pattern have been found to have greater extent of visual acuity improvement and fewer atrophic changes after intravitreal ranibizumab treatment for myopic CNV. OCTA, a novel non-invasive technique successfully detects up to 94.1% of myopic CNV.17 CNV related submacular hemorrhage can be differentiated from those caused due to lacquer cracks using this technique. OCTA features of active CNV includes typical lacy wheel pattern, numerous tiny capillaries, widely anastomosed network, and perilesional hypointense halo. Quiescent CNV are characterized by long filamentous linear large mature looking vessels, rare anastomosis and a dead tree appearance.
Several treatment choices including thermal laser photocoagulation, macular surgery and verteporfin photodynamic
therapy have previously been tried for the treatment of myopic CNV but the results of these treatment modalities are generally poor with no significant visual improvement and high risk of recurrence. Since the introduction of anti-VEGF agents in ophthalmology, anti-angiogenesis treatment with intravitreal anti-VEGF therapy has become the standard-of-care firstline treatment for myopic CNV.18 Similar to CNV in other macular diseases, increased level of VEGF has been found to be associated with myopic CNV and therefore anti-VEGF therapy is useful in myopic CNV.
The RADIANCE (The Ranibizumab and PDT [verteporfin] evaluation in myopic choroidal neovascularization) study was a 12-month, randomized clinical trial which randomized 275 patients to two regimens of intravitreal 0.5mg ranibizumab (guided by visual acuity stabilization or by disease activity) versus PDT for the treatment of myopic CNV.19 In the MYRROR study, the use of intravitreal 2mg aflibercept was compared with a sham control group for the treatment of myopic CNV. The primary outcome measure was assessed at 6 months and it was shown that intravitreal aflibercept resulted in significantly better BCVA improvement compared with sham control group, with a gain of 12.1 letters in the aflibercept group and a loss of 2 letters in the sham group. Patient with anti VEGF treatment should be kept under regular follow up to retreat in case of recurrence.
The ideal current management of patients with myopic CNV is to diagnose the myopic CNV accurately and timely so that the eye with myopic CNV can be treated with intravitreal anti-VEGF therapy as soon as possible. The main limitation of the current treatment of myopic CNV is the development of chorioretinal atrophy around the myopic CNV, thus limiting the visual improvement potential of the patients. Low vision aidsare useful for the patients with bilateral advanced vision loss.
Dome-shaped Macula
First described by Gaucher et al. in eyes with myopic posterior staphyloma. It appears as an inward bulge inside the chorioretinal posterior concavity of the eye in the macular area, which is very difficult to diagnose using fundus biomicroscopy. However, horizontal ridges connecting the optic disc and the fovea may be observed on fundus examination and these may act as an important clue to suspect. B-scan ultrasonography and OCT can effectively detect the bulge confined within the surrounding staphyloma. OCT (Vertical OCT scans in particular) is of great help in the diagnosis, typically exhibiting a convex, curved, elevated profile within the concavity of the staphyloma. The bulge is generally associated with a local thickening of subfoveal sclera. The probable causes comprise tangential vitreomacular traction, localized choroidal or scleral thickening, hypotony, and retinal resistance to scleral deformation.
Most series reported DSM in patients with mean age of 50 years or above and bilateral DSM was reported in 50% to 78% of patients.20 Visual impairment and metamorphopsia is very common in eyes with DSM. Several complications resulting in visual loss in DSM have been described, including atrophic changes in the RPE, foveal serous retinal detachment and CNV.
Macular Hole The prevalence of MH has been reported to be 8.4% in 214 eyes with pathologic myopia using OCT. Retinal detachment associated with MH (MHRD) accounts for less than 1% of all cases, although some studies from Asian population reported 9% and 21%. MHRD can either be localised at the posterior pole or extend to total rhegmatogenous RD.21 OCT is irreplaceable in differentiating between a full-thickness MH, lamellar hole, MHRD, and macular retinoschisis. Gass theorized that tangential traction of vitreous was an important factor in the pathogenesis of macular hole. The pathogenesis of MH and MHRD in high myopia is distinct from idiopathic MH, which includes anteroposterior vitreous traction on the posterior pole due to axial elongation or posterior staphyloma, tangential traction on the macula from the contraction of the cortical vitreous and epiretinal membrane; and reduced chorioretinal adhesion due to RPE atrophy. Compared to idiopathic MH, myopic MH is mostly seen in young patients. Degree of myopia and axial length has an inverse relationship with the age of onset of macular hole.
Vitrectomy is the standard procedure to treat idiopathic MH as well as MH in high myopia. ILM peeling can remove premacular tractional elements, such as vitreous cortex, epiretinal membrane; removes caffold for cellular proliferation, and increase flexibility of the retina to facilitate closure the hole. Studies of MH in high myopia with ILM peeling showed higher successful closure rate (ranging from 87 to 100%) than without ILM peeling (ranging from 60 to 77%). Inverted ILM flap technique has been reported with initial closure rate of 83.3% for treating MH in high myopia. Vitrectomy in combination with ILM peeling and a short- or long-acting gas tamponade is commonly used to treat MHRD. The retinal reattachment rate following vitrectomy for MHRD has been reported to vary widely from approximately 40% to 93%. However, MH closure rate following vitrectomy for MHRD are usually not as high as MH closure rate for MH alone in high myopia. In addition, post-operative MH enlargement has been reported due to the imbalance between the retina and choroid-sclera complex. Macular buckle, a relatively new procedure, is used by few surgeons to treat MHRD with posterior staphyloma
Figure 3: Preoperative and post operative SS-OCT showing myopic macular hole treated with pars planavitrectomy + ILM peeling.
Myopic traction maculopathy
In 1958 Phillips first reported a retinal detachment, without hole, localized to the area of a posterior staphyloma in a highly myopic eye (-20D). Forty years later, Takano and Kishi first demonstrated foveal retinal detachment and retinoschisis in severely myopic eyes with posterior staphyloma using OCT. Panozzo and Mercanticoined the term “myopic traction maculopathy (MTM)”.23 MTM, also called foveal retinoschisis, macular retinoschisis, or myopic foveoschisis, encompassesschisislike inner retinal fluid, schisis-like outer retina fluid, foveal detachment, lamellar or full-thickness macular hole and/or macular detachment.24 Myopic macular retinoschisis is reported to occur in 9% of highly myopic eyes with posterior staphyloma.25 The pathogenesis behind MTM is splitting of retina over time due to relative rigidity and noncompliance of the inner retina compared with outer retina within the posterior staphyloma. The split generally occurs at the level of the external limiting membrane. Based on the finding from OCT and surgical reports, several mechanisms have been proposed, including vitreomacular traction from partial posterior vitreous detachment, remnant cortical vitreous layer after posterior vitreous detachment, epiretinal membrane, intrinsic internal limiting membrane noncompliance, and retinal arteriolar stiffness. Therefore, MTM can be regarded as a split between the flexible outer retina and the inflexible inner retina.26-32 Visual complaints are negligible and progress slowly. To start with patients may complain of blurring of vision or metamorphopsia. Vision loss initiates with outer lamellar hole formation or early foveal detachment. OCT is an indispensable tool to diagnose MTM. Shimada et al.34 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 (Shimada et al., 2013). Although some eyes with MTM showed spontaneously resolution, several studies reported progression during its natural course from MTM to more serious complications such as foveal detachment, ranging from 3.4% to 37.5% or full-thickness MH, ranging from 0.9% to 33%. Shimada et al. further defined the progression as an increase of the extent or height of retinoschisis (more than 100 μm) or the development of an inner lamellar macula hole, foveal detachment, or full-thickness macula hole.
Figure 4: Myopic traction maculopathy with SS-OCT showing myopic retinoschisis.
Surgical techniques to treat MTM Shimada et al. showed that the progression from MTM to foveal detachment passed through four stages based on the OCT images. In stage 1, focal irregularity of the thickness of the external retina; stage 2, an outer lamellar hole and a small retinal detachment developed
stage 3, column-like structures overlying the holes separated horizontally and enlarged vertically;
stage 4, the upper edge of the external retina was further elevated and attached to the upper part of the retinoschisis layer by further enlargement of the detachment.
They recommended considering surgical treatment between stage 3 and 4. Surgery is also recommended if visual acuity decreases or additional pathology develops. Due to the possible mechanisms involved in the pathogenesis of MTM, vitrectomy is the most common treatment to release all retinal tractions, which include cortical vitreous
and epiretinal membrane. Internal limiting membrane peeling remains controversial in MTM. Although it is thought that ILM peeling is a definitive method of removing all overlying residual vitreous cortex, epiretinal membrane and cellular constituents, several studies reported full-thickness macular hole formation after vitrectomy for MTM. Gao
et al. investigated the risk factors for development of full-thickness macular holes after vitrectomy for MTM, and found that pre-operative ellipsoid zone (inner segment/outer segment) defect can be a risk factor for the development of macular hole.
In general, full-thickness macular hole or MHRD are the most common post-vitrectomy complications, which may result in unsatisfactory visual outcomes. Persistent MHs are more frequent in eyes with concomitant retinoschisis, and this seems to represent a possible risk factor for late retinal detachment in the case of unsuccessful vitreous surgery. There were some different characteristics in highly myopic eyes compared with emmetropic eyes, which include
longer axial length (AL); presence of staphyloma; presence of premacular tractional elements, such as vitreous cortex, epi-retinal membrane, and increased rigidity of internal limiting membrane (ILM); thinner sclera, choroid and retina; and presence of diffuse or patchy chorioretinal atrophy. These characteristics lead to more technically challenging surgery and are associated with lower anatomical successful rate and functional visual outcome. Using
regular instruments, surgeons may have difficulty in inducing posterior vitreous detachment, reaching the surface of the retina, removing premacular tractional elements, and doing membrane peeling, especially in eye with higher axial length (>30 mm) and the presence of posterior staphyloma. Complications may occur easily, such as iatrogenic retinal breaks while attempting to elevate or re-grasp the ILM with unmatched intraocular forceps. The thinner and fragile sclera may result in unstable intraocular pressure during the surgery which may easily cause choroidal detachment or
even suprachoroidal hemorrhage.36 Presence of diffuse or patchy chorioretinal atrophy is associated with thinner and vulnerable choroid and retina, which usually need dye to enhance contrast of the membrane and facilitate membrane peeling during the surgery. Although new technology enables visualization of microstructure and provides more information to understand the pathogenesis of myopic macular traction, the surgical and visual outcomes are still not very satisfactory. Photoreceptor layer defects and chorioretinal degeneration persist despite surgery and is the cause of unsatisfactory results
Figure 5: Preoperative and 1 month postoperative SSOCT in fovea sparing myopic traction maculopathy. The patient underwent pars planavitrectomy with ERM and fovea sparing ILM peeling. The preoperative and post-operative best corrected visual acuity were 6/36 and 6/18 respectively.
Conclusion
The prevalence of myopia is on a continuous rise. In spite of the advancements in imaging technologies and surgical
instrumentation, dealing with macular complications secondary to myopia and the resulting irreversible visual loss continues to remain a challenge. The inability to prevent the complications or slow down the progression of the
underlying pathology makes it more imperative that the ophthalmological community stays up to date about the advances in the field. This will ensure that early diagnosis and prompt and appropriate treatment is being instituted, which is the only way for us to tackle myopia at present. Special surgical instrumentation for myopic eyes, the use of intraoperative OCT, the use of upcoming diagnostic modalities like OCTA and the focus on the basic science research for preventing myopia is definitely the way forward.
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