Adrienne W. Scott,
Pathologic, or degenerative myopia, has been defined as refractive error more negative than ?6 D, and is a leading cause of blindness in Asian countries. It is a multifactorial disorder with genetic, environmental, and socioeconomic etiologies. The pathogenesis of pathologic myopia is not known. Defective collagen fibril formation results in biomechanically weak sclera and progressive globe elongation. Numerous complications, such as posterior vitreous detachment (PVD) and abnormal vitreoretinal interface, retinal detachment (RD), posterior staphyloma, macular hole, lacquer cracks (spontaneous breaks in Bruch's membrane), subretinal hemorrhage, lead to visual disability. The most common visually threatening complication of pathologic myopia is choroidal neovascularization (CNV).
Myopia-related CNV lesions are usually self-limited, and are smaller and less exudative than CNV observed in age-related macular degeneration (AMD). Argon laser has been used to treat extrafoveal CNV with a high rate of posttreatment recurrence. Photodynamic therapy (PDT) has been established as a treatment to preserve visual acuity for subfoveal myopic CNV. Antiangiogenic therapy is a promising treatment option. Surgical treatments to displace the myopic CNV have also been utilized in attempts to salvage remaining visual acuity in these eyes.
Anticholinergic therapy is being studied as a way to slow myopic degeneration. As yet, there is no proven method to prevent the axial elongation and the myriad resulting posterior segment complications described in pathologic myopia.
Myopia, or nearsightedness, is the most common ocular condition. Myopia occurs when an object image is formed anterior to the retinal surface, due to an excessively steep corneal curvature, an abnormally spherical lens, an increase in lenticular index of refraction as in nuclear sclerosis, or more commonly, as a result of increased axial length.
Pathologic, myopia occurs when progressive increase in axial length causes excessive thinning of the sclera, retina, retinal pigment epithelium (RPE) and choroid, resulting in varying degrees of visual disability. Pathologic myopia has been assigned varying definitions in the ophthalmic literature. Duke-Elder defined pathologic myopia as myopia accompanied by degenerative posterior segment changes.[2,3] Pathologic myopia has also been defined as high myopia accompanied by visual dysfunction.[3,4] The American Academy of Ophthalmology Basic Clinical Science Course defines pathologic myopia as refractive error greater than ?6 D, with axial length in excess of 26.5 mm.
Myopia is the most common refractive error and affects ~25% of adults in the United States. Various demographic characteristics have been shown to be associated with high myopia. Female gender, younger age, earlier onset of myopia, and family history are all risk factors found to be associated with an increased likelihood of progressive myopia. Increased income and educational level have been associated with high levels of myopia, likely due to their correlation with increased levels of near work.
Myopia prevalence varies among racial demographics. One study estimated prevalence of myopia in African-Americans in the United States at 13%. Recently, the Los Angeles Latino Eye Study estimated an overall prevalence of myopia in adult Latinos in one community at 16.8%, with estimated prevalence of high myopia in this community at 2.4%. A very high prevalence of myopia has been reported among Asians. Fredrick reported the overall prevalence of myopia to be as high as 70-90% in Asian populations. While 0.2-0.4% of the US population was found to have refractive error greater than ?7.9 D, the prevalence of pathologic myopia in Asian countries has been reported to be as high as 1%.
It is well accepted that pathologic myopia is characterized by progressive scleral thinning with localized ectasia. The exact pathogenesis of pathologic myopia, however, is not entirely understood. It is postulated that myopic sclera is biomechanically weak and has been demonstrated to alter its composition and rigidity in response to environmental and visual stimuli. Remodeling of extracellular matrix by matrix metalloproteinases and their tissue inhibitors leads to abnormalities in collagen fiber bundles and a reduction in the size of individual collagen fibers in myopic eyes. Myopia has been induced in animal models by defocusing the retinal image, triggering a cascade of events that leads to axial elongation. Cholinergic pathways have been studied as mediators of scleral elongation associated with myopia. Other neurotransmitters such as dopamine, vasoactive intestinal peptide, and glucagon have also been implicated as possible mediators of scleral growth.
A variety of ocular morbidities such as low-tension glaucoma, amblyopia, strabismus, early cataract formation, image minification, decreased contrast sensitivity, and visual field defects have all been associated to occur in association with pathologic myopia. Stickler syndrome, Wagner syndrome, Ehlers-Danlos syndrome, and Marfan's syndrome are hereditary conditions that have been associated with axial high myopia.
The fundus changes observed in conjunction with pathologic myopia most notably lead to visual deterioration and blindness in highly myopic individuals. A trademark of the myopic posterior segment clinical examination is the tessellated, or tigroid fundus, in which choroidal vessels are evident below the thinned, atrophic retina and RPE (Fig. 154.1). This and other abnormal posterior segment findings in pathologic myopia were described in a large, retrospective, histopathologic examination of enucleated eyes with degenerative myopia by Grossniklaus and Green. Myopic configuration of the optic nerve head was the most frequently associated finding, present in 37.7% of eyes. Posterior staphyloma and vitreous degeneration were the next most frequently observed findings.
FIGURE 154.1 Typical fundus appearance of pathologic myopia. This patient has 20/60 vision with ?20 D correction. Note tilted optic nerve with peripapillary crescent, tigroid fundus appearance, attenuated vessels, and chorioretinal atrophy.
Pathologic myopic retinopathy is particularly visually devastating, as it is irreversible, often bilateral, and affects individuals at younger ages during their productive years. The major visually threatening complications of myopic retinopathy are discussed below.
POSTERIOR VITREOUS DETACHMENT
Highly myopic eyes are characterized by premature posterior vitreous detachment (PVD). The incidence of PVD in highly myopic patients has been strongly correlated with increased axial length, age, and degree of myopia compared to controls. A PVD is often preceded by vitreous syneresis, and the formation of fluid pockets within the vitreous gel. Acute PVD may produce photopsia and a symptomatic 'floater', in which shadows are cast on the retinal surface as a result of vitreous condensation and opacification. Detachment of the posterior vitreous may also cause acute vitreous hemorrhage if retinal vessels are avulsed at the time of posterior vitreous separation. A PVD may cause retinal traction and lead to a retinal break as well as the most common surgical complication of high myopia-rhegmatogenous retinal detachment (RRD).
A break in the retina causes liquified vitreous fluid to travel underneath the retina into the subretinal space, detaching the retina. RRD may result from a retinal tear, retinal dialysis, macular hole, or as a result of acute PVD as described previously. In the general population, the retinal detachment incidence is less than 1%, RRD occurs more frequently in eyes with increased axial length. This increased likelihood of RRD in high myopes is due to peripheral retinal abnormalities such as lattice degeneration, increased frequency of PVD, and an abnormal vitreoretinal interface caused by increased axial length.
RRD as a result of macular hole formation is more likely to occur in eyes with pathologic myopia (Fig. 154.2). One study reported 6.3% of highly myopic eyes to develop an asymptomatic macular hole, confirmed by ocular coherence tomography (OCT).
FIGURE 154.2 RD resulting from a macular hole (black arrow) in a patient with pathologic myopia.
High myopia also predisposes eyes to RRD after cataract surgery. Highly myopic eyes undergoing cataract surgery are more likely to develop a postoperative retinal detachment when compared to controls. Pars plana vitrectomy (PPV) with or without scleral buckling, with or without gas or silicone oil tamponade may be used to repair RRD.
Globe elongation leads to characteristic optic nerve changes. The tilted optic nerve is often seen in eyes with pathologic myopia. Thinning of the retina and RPE leads to the peripapillary temporal crescent observed to surround the optic nerve head (Fig. 154.1). A recently described optic nerve finding is peripapillary detachment. Freund and colleagues reported peripapillary detachment as an elevated, yellow-orange lesion inferior to the optic disk seen in highly myopic eyes. OCT demonstrated a localized retinal pigment epithelial detachment corresponding to the lesion. Peripapillary detachment was not observed to be visually significant. In another study, peripapillary detachment was present in as many as 4.9% of highly myopic eyes and was associated with glaucomatous optic nerve defects in 71% of eyes.
Localized, progressive globe elongation and resulting scleral ectasia leads to the development of a posterior staphyloma, another hallmark of degenerative myopia (Fig. 154.3). The prevalence of staphyloma formation correlates with axial length. Posterior staphyloma may cause visual field deficits, and central visual acuity may be affected if the staphyloma involves the macula. Increased likelihood of retinal detachment and formation of macular hole have been associated with posterior staphyloma formation in a study by Oie and colleagues.
FIGURE 154.3 OCT in a patient with pathologic myopia. Visual acuity is 20/200 with a spherical equivalent of ?22 D. Note the posterior staphyloma, and the hyperreflectivity of the tissues underlying the atrophic retina. A partial PVD overlies the macula.
Excessive tissue stress in pathologic myopia may also result in lacquer crack formation - focal, linear breaks in Bruch's membrane. Lacquer cracks may cause spontaneous subretinal hemorrhage (Fig. 154.4) at the time of formation, and may produce symptoms of acute photopsia, metamorphopsia, or scotoma. A later complication of lacquer crack formation is the development of secondary CNV.
FIGURE 154.4 Subretinal hemorrhage in a myopic eye. This ?11.5 D myopic patient experienced a decrease in vision to 20/80 from submacular hemorrhage.
Macular CNV occurs in 5-10% of eyes that are highly myopic[21,22] and is the most common visually threatening complication of pathologic myopia.[3,23-25] In its later stages, CNV due to pathologic myopia may be called a Fuchs spot. Foerster also described hemorrhagic lesions in myopic eyes which may describe a different stage in myopic CNV formation.[26,27] It has been observed that CNV in persons younger than 50 is seen most often in conjunction with pathologic myopia.
NATURAL HISTORY OF MYOPIC CNV
The natural history of myopic CNV is variable. Yoshida and colleagues reported a generally poor prognosis for these untreated eyes with vision decreasing to worse than 20/200 at 10-year follow-up. The same group also reported favorable characteristics of highly myopic eyes with CNV, which include younger age at onset, smaller CNV lesion size, and juxtafoveal location. Degree of myopia did not appear to influence prognosis in this study. Myopic CNV appears to be a self-limited process with low activity and rapid absorption. It is, however, the development of chorioretinal atrophy around the myopic CNV that has been observed to enlarge, involve the fovea in some cases, and cause a further decrease in visual acuity.[24,31]
MEDICAL TREATMENTS OF MYOPIC CNV
Treatment modalities aimed toward treating CNV related to age-related macular degeneration (AMD) have been applied to the treatment of CNV in myopic eyes. CNV does, however, differ between these two groups in that most CNV lesions in association with pathologic myopia are classic, less exudative, and smaller as compared to CNV lesions in AMD. Laser photocoagulation was the primary available treatment option for myopia-associated CNV prior to the 1990s.[3,19,32-36] Laser photocoagulation has shown short-term efficacy in limiting the extension of the extrafoveal or juxtafoveal CNV. A long-term study comparing the natural history of myopic CNV with laser treatment found that the visual acuity was preserved only after the first 2 years of follow-up. At 5-year follow-up, there was no significant difference in visual acuity between treated and untreated eyes. The CNV is subject to recur along the border of the laser scar in treated eyes, with recurrence rates reported as high as 31-72%.[3,26-30,32-35] In addition to the immediate scotoma formation caused by laser treatment, further loss of central visual acuity may result in laser-treated myopic eyes with laser scar expansion, a process known as 'atrophic creep'.
Photodynamic therapy (PDT) with verteporfin has been a major treatment option in eyes with myopia-related subfoveal CNV. PDT involves the administration of an intravenous photosensitive verteporfin dye which selectively accumulates in the CNV lesion. Diode laser is then used to activate the accumulated dye and cause occlusion of the choroidal neovascular vessels. Two-year data from the Verteporfin in Photodynamic (VIP) Therapy Study Group showed maintained visual benefit of the PDT-treated group as compared to the placebo therapy group at 2-year follow-up. Other studies have corroborated the VIP data, observing that PDT can increase the chance of visual stabilization or improvement compared with placebo. Intravitreal corticosteroids are also being considered in myopic CNV therapy in conjunction with PDT. Though PDT has been shown to have a treatment benefit in highly myopic CNV lesions, as with thermal laser treatment, the potential exists for posttreatment RPE damage, and posttreatment laser expansion of chorioretinal atrophy in the myopic eye after PDT treatment.
Angiogenic growth factors such as vascular endothelial growth factor (VEGF) are implicated in the pathogenesis of ocular neovascularization in the human eye.[40,41] As in the case of neovascular AMD, VEGF inhibition is being studied as a treatment modality in myopia-related CNV. Clinical trials are currently underway to evaluate anti-VEGF therapy in pathologic myopia.
SURGICAL TREATMENTS FOR MYOPIC CNV
Surgical removal of CNV in pathologic myopia has been performed.[43,44] No significant improvement in visual acuity has been reported, and surgical extraction of myopic CNV has been associated with high recurrence rates and postsurgical RPE atrophy.[3,43-46]
Another surgical intervention, macular translocation, is a complex surgical procedure first described as a treatment for macular degeneration by Machemer and Steinhorst.[3,46] Macular translocation involves moving the overlying sensory retina from the subfoveal CNV bed to a new location overlying healthy RPE.
Proliferative vitreoretinopathy has been a frequent postoperative complication. Further study is needed to establish the role of macular translocation in the treatment of myopic CNV.
The treatments mentioned previously are all dedicated to mitigating the visual disability due to complications of pathologic myopia. There is no known cure for the globe elongation responsible for the complications experienced by those with pathologic myopia. Prevention of myopic degeneration has been attempted with anticholinergic agents, such as atropine[47,48] and pirenzipine, that have been studied as possible therapeutic agents to slow scleral growth in humans.
Scleral reinforcement surgery has been attempted to arrest the axial globe elongation which occurs in pathologic myopia.[1,50] The clinical benefit of these procedures has as yet been unproven in a randomized, controlled clinical trial.
Refractive surgery procedures, such as laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and radial keratotomy (RK), have achieved emmetropia in high myopes through alterations of corneal architecture. Phakic refractive lenses and cataract surgery have also been utilized to minimize myopic refractive error. These procedures, however, do not eliminate the myriad posterior segment complications that threaten the visual acuity of high myopes.
High myopia is a multifactorial disorder, with environmental, socioeconomic, and genetic factors playing a role in myopic degeneration. An X-linked form of pathologic myopia has been described, and Young and associates have identified a chromosomal locus for autosomal dominant high myopia. Discovery of other genes involved in high myopia may make gene therapy a potential area for future treatment.
Treatment Options for Myopic CNV
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