Pathologic myopia (myopic degeneration)

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Pathologic myopia (myopic degeneration)
Classification and external resources
DiseasesDB 32401


Disease Entity

Pathologic Myopia (Myopic Macular Degeneration)

Disease

Pathologic myopia represents a subgroup of myopia and affects up to 3% of the world population.[1]  Vision loss related to pathologic myopia is of great clinical significance as it can be progressive, irreversible and affects individuals during their most productive years.  High myopia is defined as refractive error of at least -6.00D or an axial length of 26.5mm or more[1].  Pathologic or degenerative myopia is defined as high myopia with any posterior myopia-specific pathology from axial elongation."[1][2] The overall global prevalence is estimated to be 0.9-3.1% with regional variability.  The prevalence of pathologic myopia-related visual impairment has been reported as 0.1%-0.5% in European studies and 0.2% to 1.4% in Asian studies.[3]

Etiology

Biomechanical forces related to axial elongation of the eye result in stretching of the ocular layers and progressive thinning of the retina, choroid and sclera.[1]

Risk Factors

Primary risk factors for pathologic myopia include greater axial length and age.  Additional possible risk factors such as female gender, larger optic disc area and family history of myopia have been suggested by additional studies.[1][2][3]

History

Patients may describe needing to wear thick glasses as a child or slowly progressive vision loss.  They may endorse new metamorphopsia or scotoma when vision-limiting macular complications develop.

Physical examination

Assessment of visual acuity, intraocular pressure, pupillary reaction and dilated fundus exam are essential.  A thorough macular examination and peripheral depressed examination are key to detecting complications related to pathologic myopia. In particular, lacquer cracks, myopic schisis, or choroidal neovascularization in the macula area and holes or tears in the periphery of the retina. Assessment of visual fields and Amsler grid testing may be beneficial.

Signs

Progressive retinal pigment epithelial (RPE) thinning and attenuation develops in various clinical changes throughout the fundus.  A tessellated appearance corresponding to irregular distribution of RPE atrophy and variable light reflection may be appreciated even in young patients with high myopia.  When RPE attenuation surrounds the optic disc, this hypo-pigmented finding is described as peri-papillary atrophy.

Commonly the optic disc has an oval appearance en-face and is referred as a tilted disc.  The optic nerve appears to insert into the elongated globe at an angle.  The tilted appearance is characterized by temporal flattening of the disc due in part to peri-papillary scleral expansion. As a result, a hypo-pigmented myopic crescent or a myopic cone is seen where sclera is directly visible.  In intermediate disease, choroidal vessels will be seen beneath atrophic RPE however with progressive disease the choroid itself also atrophies and the choroidal vessels may become less noticeable.

Lacquer cracks are irregular yellow-appearing bands often seen in the posterior pole and are present in 4.2% of eyes with an axial length of at least 26.5mm.[1]  These represent breaks in Bruch’s membrane and may be foci of future choroidal neovascularization (CNV). Over time these breaks can expand and stretch and in late stages may resemble the appearance of geographic atrophy similar to that seen in advanced non-neovascular Age-related Macular Degeneration (AMD)

Fuchs spots (also referred to as Forster-Fuchs spots) are areas of RPE hyperplasia suspected to be the response of the RPE to previous regressed CNV. 

Staphyloma development, characterized by outpouching of scleral tissue, typically involving the optic disc or the macula, is a common occurrence, estimated in 35% of eyes with high myopia.[4]  This can be difficult to appreciate with bio-microscopy but is evident on Optical Coherence Tomography (OCT) or B scan ophthalmic ultrasound.  Staphylomata are commonly associated with lacquer cracks, RPE attenuation, epiretinal membrane and macular or foveal schisis

Symptoms

Patients may be asymptomatic during the slowly progressive attenuations of the RPE and choroid.  In the cases where central CNV or foveal schisis develop, the patient may note a focal area of blurring, metamorphopsia or scotoma that can rapidly cause serious decline in central vision.  Peripheral CNV may go undetected. 

Clinical diagnosis

Diagnosis is based on fundus examination with identification of characteristic features, lack of more plausible cause for the degeneration and diagnostic testing as described below.

Diagnostic procedures

Fluorescein Angiography is useful for evaluating myopic patients for development of CNV.  Early images may show transmission defect in patches or areas of RPE atrophy at the macula and/or around the optic disc.  Angiography can identify lacquer cracks in early and transit phases by linear distribution of transmission defect.  

In pathologic myopia, the development of CNV tends to be smaller and less exudative compared to CNV seen in AMD.   Myopic CNV may appear as a focus of hyperfluourescence with a rim of hypoflourescence corresponding to hyperpigmentation at the border of the lesion.  Any associated hemorrhage will result in blocked fluorescence.  Leakage is seen in late images with or without blurring of the pigmented rim.  The leakage present with myopic CNV is more subtle leakage that with CNV related to AMD and it is common that the CNV leakage may be partially or completely obscured by overlying subretinal hemorrhage.     Indocyanine green angiography (ICG) may be more sensitive for detecting CNV as the vascular leakage in pathologic myopia is typically less prominent than for AMD-related pathology and can be more easily missed on fluorescein angiography.  Despite subtler findings on imaging studies with myopic CNV compared to those AMD related CNV, patients often note that these smaller lesions alter the visual perception significantly.

Presently, spectral domain OCT (SD-OCT) is the preferred method of following myopic CNV over time.  Although FA or ICG is more sensitive for detection, SD-OCT is a non-invasive, quantifiable and widely available method for monitoring CNV.  The CNV will be visible as a subretinal hyper-reflective lesion with or without intraretinal fluid, subretinal fluid or pigment epithelial detachment.   The physical topography of staphyloma and thinned retinal layers pose challenges to interpreting OCT in the myopic patient however the resolution is appropriate for most patients. The role of OCT angiography in pathologic myopia is being investigated at present.

Spectral Domain OCT also allows for detection of myopic or foveoschisis or macular hole formation.  For this reason, evaluating patients with SD-OCT permits better demonstration of the macular anatomy compared to a bimoscosopic examination.[2]

Management

Patients with stable high myopia may be followed annually for visual acuity, refraction and general ophthalmic health.  In the case of development of CNV or other complication patients are followed more closely, as directed by their treatment regimen. 

Medical therapy

There is no topical, local or systemic pharmacotherapy or surgery that is known to alter effectively the increase in axial length and the thinning of scleral choroid and retina of pathologic myopia. There are, however, treatments available for CNV, a major complication of pathologic myopia. 

The first widely adopted therapy for CNV in pathologic myopia was photothermal laser ablation of the new vessels.  This treatment was complicated by a high rate of recurrence and the tendency of the photocoagulation scars to expand over time and significantly risked central vision as the border of the laser scar encroached or expaned into the fovea.[2]

Photodynamic therapy (PDT) replaced thermal laser in the later 1990s, supported by evidence in the Verteporforin in Photodynamic Therapy (VIP) study.  The advantage of PDT was the potential to selectively target neovascular vessels with lesser collateral damage to the retina, RPE and choroid and to limit the development of large scars seen in photothermal laser treatment.  The VIP study showed that PDT was better than placebo in reducing moderate vision loss at 12 months however by 24 months there was no statistically significant difference between treatment arms.[1]  Photodynamic Therapy has been limited by the observation that up to 13% still have moderate vision losses despite treatment and up to 57% with persistent leakage at one year.  

Anti-VEGF therapy is now considered first line intervention in patients with myopic CNV.[2]  The initial evidence was based primarily on retrospective studies and clinician experience.  Anti-VEGF is currently used off-label for the treatment of myopic CNV.  A growing number of prospective and randomized trials have been published or are currently underway.  One such trial was RADIANCE (A Randomized Controlled Study of Ranibizumab in Patients with Choroidal Neovascularization Secondary to Pathologic Myopia), a multi-center, randomized controlled trial comparing intravitreal ranibizumab to PDT in the treatment of myopic CNV.  This study reported improved visual acuity at 12 months in the ranibizumab treatment arm.[5]   More studies are needed to evaluate the long-term effects of anti-angiogenic therapy in this setting.  Current data indicate that patients are more likely to have clinical response and resolution of CNV within 1-3 injections as compared to long-term monthly injections in macular degeneration complicated by CNV.[5]

Surgery

Patients with decreased vision in the setting of maculoschisis or foveoschisis may benefit from vitrectomy to relieve traction on the fovea and prevent formation of macular holes or macular retinal detachment.  This is further discussed in the article myopic traction maculopathy. Patients with maculoschisis complicated by macular holes or significant chorioretinal atrophy have a worse visual prognosis however overall 80% of those with foveal detachment and 50% of those with retinoschisis may have improved vision following surgery.[1]  Gas or silicon tamponade is essential in cases of macular hole with or without detachment as this encourages re-apposition of retinal layers. Internal limiting membrane peeling, likewise, is seen as an important asset for relief of traction and improved macular hole closure rates.

Retinal detachments may develop however if confined to the area of staphyloma these may be monitored without intervention.  Prompt surgery is indicated if any progression is identified.  The use of a macular buckle to treat the staphyloma as well as ongoing vitreous traction or detachment is reported to have higher foveal reattachment rates than vitrectomy alone in cases of recurrent detachment.  Direct macular buckling even without vitrectomy has had good rates or retinal re-attachments, likely because of alteration of distribution of vector forces allowing for improved contact of RPE with neurosensory retina, however this approach is generally considered second-line due to post-operative complications such as metamorphopsia and alteration of choroidal circulation. The role of macular buckling is still controversial.

Complications

Complications associated with visual morbidity in pathologic myopia include progressive thinning and atrophy resulting in photoreceptor loss, development of choroidal neovascular membranes, pigment epithelial detachments and macular or foveal detachments.  Ninety-percent of patients with CNV are expected to have atrophy surrounding any previously regressed CNV.[1]  Peripheral retinal detachment is another complication.

Prognosis

Progressive visual decline in the form of progressive chorioretinal thinning, atrophy and stretching of existing scars is expected in about 40% of patients with pathologic myopia. [1]

Additional Resources

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 Ryan et al.  Retina. 2013
  2. 2.0 2.1 2.2 2.3 2.4 Adatia FA, Luong M, Munro M et al. The Other CNV: A review of myopic choroidal neovascularization treatment in the age of anti-vascular endothelial growth factor agents.” Survey of Ophthalmology. 2015 60; 204-215. Epub 2014 Nov 5
  3. 3.0 3.1 Wong TY,  Ferreira A, Hughes R et al.  Epidemiology and Disease Burden of Patholoic Myopia and Myopic Choroidal Neovascularization: An Evidence Based Systemic Review.  American Journal of Ophthalmology. 2014; 15:9-25.
  4. Raecker ME, Park DW, Lauer AK.  “Diagnosis and Treatment of CNV in Myopic Macular Degeneration.” Eyenet 2015; 4:35-37.
  5. 5.0 5.1 Wolf et al. RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia.”  Ophthalmology. 2014 Mar;121(3):682-92.  Epub 2013 Dec 8.