Pathologic myopia (myopic degeneration)

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Pathologic myopia (myopic degeneration)
Pathologic myopia with tilted disc and peripapillary atrophy of RPE and choroid.
Pathologic myopia with tilted disc and peripapillary atrophy of RPE and choroid.

© 2020 American Academy of Ophthalmology.[1]


Disease Entity

Pathologic Myopia (Myopic Macular Degeneration)

Disease

Pathologic myopia represents a subgroup of myopia and affects up to 3% of the world population.[2]  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[2].  The definition of pathologic myopia in early studies has been inconsistent and mostly revolved around a combination of refractive error and axial length, which may simply reflect a high degree of myopia. Additionally, there was no clear evidence for the cutoff values chosen. In recent years, the definition of pathologic myopia has shifted to "the presence of myopic maculopathy equal to or more severe than diffuse chorioretinal atrophy."[3] Myopic maculopathy includes diffuse chorioretinal atrophy, patchy chorioretinal atrophy, lacquer cracks, myopic choroidal neovascularization (myopic CNV), and CNV-related macular atrophy.

Epidemiology

The overall global prevalence is estimated to be 0.2-3.8% with regional variability, but varying definitions of pathologic myopia used in early epidemiological studies may limit the comparability of findings.[4] 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.[5]

Pathophysiology

The main factors proposed for driving the development of pathologic myopia are elongation of the axial length and posterior staphyloma.[6] 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.[2]

Risk Factors

Both environmental and genetic factors play a role in the development of myopia, which is further discussed in the corresponding article. Currently, the roles of known myopia-associated genetic variants have not been well established in the development of pathologic myopia.[7] Primary risk factors for pathologic myopia include older age, greater axial length, and higher myopic spherical equivalent.[4]  Additional possible risk factors such as female gender, larger optic disc area and family history of myopia have been suggested.[2][8][5] The role of education level in the development of pathologic myopia is currently unclear.[4][9]

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.

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. 

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.[2]  These represent breaks in Bruch’s membrane and may be foci of future choroidal neovascularization (CNV). It has been reported that among patients with lacquer cracks, 29.4% eventually develop CNV. [10] 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 spot (also referred to as Forster-Fuchs spots) is an area of RPE hyperplasia suspected to be the response of the RPE to previous regressed CNV. Myopic CNV is the most common cause of vision loss in high myopia and has been reported in 5% to 10% of cases of pathologic myopia.[10][11] 

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.[12]  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

Classification

Given the lack of centralized definition and terminology for pathologic myopia, an international group of experts in high myopia developed a simplified, systematic classification based on a meta-analysis of pathologic myopia (META-PM).[13] Myopic maculopathy was classified into five different categories based on atrophic change.

  • Category 0: no macula degenerative lesion
  • Category 1: tessellated fundus only
  • Category 2: diffuse chorioretinal atrophy
  • Category 3: patchy chorioretinal atrophy
  • Category 4: macular atrophy


Recently, it has been noted that many patients with macular changes from pathologic myopia are not sufficiently represented by a atrophy-centred classification system. A newly proposed ATN classification system for myopic maculopathy includes atrophic (A), tractional (T) and neovascular (N) components.[6]

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.  

Spectral domain OCT (SD-OCT) has been 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. 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.[8] The role of OCT angiography in pathologic myopia is being investigated at present.

Recently, swept source and ultra-widefield (UWF) OCT have been implemented in evaluating various tissues affected by pathologic myopia. Swept-source OCT uses a wavelength-sweeping laser as the light source and has less sensitivity roll-off with tissue depth than conventional spectral-domain OCT. Using a longer central wavelength, penetration into deeper tissues and evaluations of the choroid and sclera are potentially possible. UWF-OCT is similar to swept source OCT but uses multiple scan lines to generate scan maps, which has been utilized to visualize posterior staphylomas, myopic macular retinoschisis, and dome shaped macula. The data provided by these newer imaging techniques may help in understanding the pathophysiology of pathologic myopia as well as new therapeutic approaches.[14]

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. Animal and in-vitro studies have shown some promise in scleral collagen crosslinking to arrest the progression of pathologic myopia but further research is needed to elucidate these effects.[15] 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 expanded into the fovea.[8]

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.[2]  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.[8]  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.[16]   The REPAIR study (Prospective, Multi-center Trial of ranibizumab in Choroidal Neovascularization due to Pathological Myopia) also demonstrated the efficacy and safety of ranibizumab in myopic CNV.[17] Meanwhile, the MYRROR study (Intravitreal Aflibercept Injection in Patients with Myopic Choroidal Neovascularization) found aflibercept to be efficacious and safe in myopic CNV of an Asian population.[18] 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.[16]

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.[2]  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. It has also been suggested that concomitant resolution of foveoschisis, retinal reattachment, and macular hole closure has been achieved more frequently with macular buckle than with vitrectomy.[15] However, 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, macular hole, pigment epithelial detachments and macular or foveal detachments.  Ninety-percent of patients with CNV are expected to have atrophy surrounding any previously regressed CNV.[2]  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. [2] In one study over a 6-year period, 1.2% of myopic eyes developed pathologic myopia and 17% with existing pathologic myopia experienced progression. Baseline myopia severity and axial length were strong predictors of worsening prognosis, and these factors were associated with poorer visual acuity and vision-related quality of life.[19]

References

  1. American Academy of Ophthalmology. Pathologic myopia with tilted disc and peripapillary atrophy of RPE and choroid. https://www.aao.org/image/pathologic-myopia-with-tilted-disc-peripapillary-a-2 Accessed May 19, 2020.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Ryan et al.  Retina. 2013
  3. Ohno-Matsui K. Pathologic myopia. Asia Pac J Ophthalmol 2016;5: 415–423.
  4. 4.0 4.1 4.2 Wong YL, Sabanayagam C, Ding Y et al. Prevalence, Risk Factors, and Impact of Myopic Macular Degeneration on Visual Impairment and Functioning Among Adults in Singapore. Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4603-4613.
  5. 5.0 5.1 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.
  6. 6.0 6.1 Ruiz-Medrano J, Montero JA, Flores-Moreno I, et al. Myopic maculopathy: current status and proposal for a new classification and grading system (ATN). Prog Retin Eye Res. 2019 Mar;69:80-115
  7. Wong YL, Hysi P, Cheung G, Tedja M, Hoang QV, Tompson SWJ, et al. (2019) Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium. PLoS ONE 14(8): e0220143.
  8. 8.0 8.1 8.2 8.3 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
  9. Liu HH, Xu L, Wang YX, Wang S, You QS, Jonas JB. Prevalence and progression of myopic retinopathy in Chinese adults: the Beijing Eye Study. Ophthalmology. 2010;117:1763–1768.
  10. 10.0 10.1 Spaide et al. Pathologic Myopia. 2014
  11. Neelam K, Cheung CM, Ohno-Matsui K, Lai TY, Wong TY. Choroidal neovascularization in pathological myopia. Prog Retin Eye Res. 2012;31(5):495–525. PubMed PMID: 22569156.
  12. Raecker ME, Park DW, Lauer AK.  “Diagnosis and Treatment of CNV in Myopic Macular Degeneration.” Eyenet 2015; 4:35-37.
  13. Ohno-Matsui K, Kawasaki R, Jonas JB et al. International photographic classification and grading system for myopic maculopathy. Am J Ophthalmol. 2015 May;159(5):877-83.e7. Epub 2015 Jan 26.
  14. Ohno-Matsui K et al. Imaging of pathologic myopia. Asia Pac J Ophthalmol (Phila) 2019;8:172–177
  15. 15.0 15.1 Saw SM, Matsumura S, and Hoang QV. Prevention and Management of Myopia and Myopic Pathology. Invest Ophthalmol Vis Sci. 2019 Feb 1;60(2):488-499.
  16. 16.0 16.1 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.
  17. Tufail A, Narendran N, Patel PJ et al. Ranibizumab in myopic choroidal neovascularization: the 12-month results from the REPAIR study. Ophthalmology. 2013 Sep;120(9):1944-5.e1.
  18. Ikuno Y, Ohno-Matsui K, Wong TY et al. Intravitreal Aflibercept Injection in Patients with Myopic Choroidal Neovascularization: The MYRROR Study. Ophthalmology. 2015 Jun;122(6):1220-7. Epub 2015 Mar 4.
  19. Wong YL, Sabanayagam C, Wong CW et al. Six-Year Changes in Myopic Macular Degeneration in Adults of the Singapore Epidemiology of Eye Diseases Study. Invest Ophthalmol Vis Sci. 2020;61(4):14.