Continuing Education Activity

Pathological myopia is a group of conditions related to high myopia. It results from excessive growth in the length of the eye leading to biomechanical stretching of the retina, choroid, and sclera. This activity outlines the presentation and management of the various manifestations of pathological myopia.

Objectives:

• Describe the pathophysiology of pathological myopia.
• Describe the typical imaging findings associated with myopic choroidal neovascularization.
• Outline the treatment of myopic choroidal neovascularization.
• Explain the common physical exam findings in pathological myopia.

Introduction

Myopia, colloquially referred to as shortsightedness or nearsightedness, is one of the most common global eye diseases. It occurs when the optical power of the eye is too high for the corresponding axial length of the eye, resulting in images of distant objects being focused in front of the retina. Myopia can be corrected by wearing glasses, contact lenses, or refractive surgery. However, pathologic myopia (PM) refers to a subset of ocular conditions associated with high myopia. The exact diagnostic criteria of PM have not been established. Some have defined PM based on an absolute cutoff value of refractive power (-6 to -8D) or axial length (26.5mm), while others have based it on the presence of myopic maculopathy.[1][2]

Etiology

Myopia is attributable to a complex interaction between genetics and the environment. Familial clustering in myopia is evident in twin studies and high sibling risk ratios.[3] Several genetic variants have been associated with the development of myopia. For the syndromic myopias, which include Marfans and Sticklers syndrome, the implicated genes are involved in the extracellular matrix of the sclera. Gene studies have identified 25 different genetic loci in association with non-syndromic myopia. The pathogenicity of genetic mutations is difficult to identify due to variable gene expression and interactions.[4]

There is some evidence to suggest that spending more time outdoors is protective against the development of myopia.[5] Likewise, a shift towards urbanization and higher education is thought to be a significant driver of the increasing prevalence of myopia among schoolchildren.[6] The predominating theory is that the increased time spent accommodating during near reading promotes signals for eye growth. Animal studies have also found the placement of both positive and negative lenses that defocus images on the retina can promote or inhibit eye growth.[7][8]

Epidemiology

The prevalence of myopia varies according to ethnicity and geography. The prevalence of myopia is highest in regions of East Asia (47%) and Southeast Asia (39%) as compared to Central Europe (27%) and Central Africa (7%).[9] There are also observed differences in the prevalence of myopia between urban and rural areas, which is attributed to the socio-economic and educational systems in place.[8] The prevalence of pathologic myopia is reportedly from 0.9% to 3.1%.[10]

Pathophysiology

Myopia develops in the early to middle childhood years and continues to early adulthood. Most children are born hyperopic. Then, closer to the age of 5-8, they experience a shift in their refraction through a process termed emmetropisation. After this process, the cornea stabilizes but increases in axial length lead to progressive myopia.[11] In addition to longer axial lengths, individuals with pathological myopia typically manifest different ocular shapes with irregular protrusions, termed staphylomas. Excessive axial elongation stretches and thins the retina, choroid, and sclera, which results in various pathological findings.

History and Physical

A complete history should take place focusing on specific ocular and systemic associations of high myopia. A review of systems focused on joint, hearing, and heart problems should be conducted to screen for an underlying connective tissue disorder. Family history and previous ocular surgery should also be elicited, paying attention to any previous retinal detachments, corrective lens wear, or refractive surgery. New complaints of metamorphopsia, scotoma, flashes, and onset of new floaters suggest retinal pathology.

Physical examination should begin with measuring visual acuity, intraocular pressure, and assessing pupillary reaction. Next, a dilated fundal examination focused on the macula, optic disc, and peripheral retina should be performed. Finally, an assessment of visual fields can be requested if glaucoma is suspected.

 In 2015, a universal classification system for pathological myopia was developed by a specialist panel of researchers.

Proposed Classification of Myopic Maculopathy. Proposed by Meta-analysis for Pathologic Myopia (META-PM) Study Group.[2] 

Findings

• Staphyloma is an outpouching of the wall of the eye. Posterior staphyloma is unique to pathological myopia. Posterior staphylomas associated with pathological myopia have been classified into ten different types based on shape and location.[12] 
• Lacquer cracks are irregular yellow linear lesions in the macula. They represent mechanical linear breaks in Bruch’s membrane and serve as potential foci for choroidal neovascularisation. Newly formed lacquer cracks may be associated with hemorrhage.
• Myopic choroidal neovascular membrane (CNV) is a common cause of visual impairment in patients with pathological myopia. The incidence of myopic CNV is estimated to be 10%, but it is even higher (35%) if the fellow eye was previously affected. Myopic CNV typically appears as a small, gray subretinal lesion beneath or near the fovea, and it may be associated with subretinal fluid or hemorrhage. Fuchs spots are pigmented gray scars that correspond to sites of regressed myopic CNV.
• Myopic tractional maculopathy results from vitreoretinal traction with manifestations that include retinoschisis, foveal retinal detachment, and lamellar or full-thickness macular hole.
• A dome-shaped macula is an inward bulge around the foveal region associated with scleral thickening. It is present in 20% of eyes with high myopia.[13]
• Structural anomalies and atrophy around the optic nerve fibers and optic disc pits can result in visual field loss.[14]
• Peripheral retinal holes or breaks.

Evaluation

Spectral-domain optical coherence topography (OCT) is non-invasive, quick, and widely available. It is suitable for diagnosing and monitoring retinal pigment epithelium atrophy, myopic CNV, and myopic tractional maculopathy. OCT provides a regular measurement of retinal and choroidal thickness, plus the presence of subretinal or intraretinal fluid. It also highlights the presence of macular holes, retinoschisis, or detachments. Dome-shaped maculopathy is best visualized on radial or vertical OCT slices.

Fluorescein angiography (FA) provides detailed information about the type and activity of myopic CNV and helps plan treatment. Myopic CNV resembles the appearance of type 2 or classic CNV on FA, demonstrating early hyperfluorescence that increases in size and intensity through to the late phase. It can help differentiate between hemorrhage from a myopic CNV versus a lacquer crack, with the latter displaying blocked fluorescence instead of increasing hyperfluorescence.

Other tests such as OCT angiography, ultrasonography, magnetic resonance imaging, and Indocyanine Green Angiography may be useful at evaluating the shape and perfusion of the retina and choroid. However, these tests are rarely utilized in a clinical setting.[15][16][17]

Treatment / Management

Simple myopia can be satisfactorily corrected using various refractive lenses (contact lenses, spectacles) or refractive surgery. Incentives to encourage outdoor play among children may help prevent myopia progression. Other methods include specialized contact lenses and low-dose topical atropine.[18] However, no proven therapy can reverse or halt the progressive retinal atrophy associated with pathological myopia.

The mainstay treatment of myopic CNV is anti-vascular endothelial growth factors (anti-VEGF) intravitreal injections. Large, randomized control trials have demonstrated superior visual and anatomical outcomes with anti-VEGF therapy compared to photodynamic therapy or control.[19][20] Fewer treatments with anti-VEGF therapy are needed for disease control compared with other subtypes of CNV (age-related macular degeneration).[19]

The management for myopic tractional maculopathy remains debatable and depends on specific OCT findings.[21] Some practitioners favor a conservative approach as some cases will remain stable or resolve following the release of retinal traction. However, those with pre-existing extensive macular retinoschisis may be more likely to progress and require intervention.[22] The surgical approaches consist of pars plana vitrectomy +/- internal limiting membrane peel versus a macular buckle procedure.

Differential Diagnosis

• Age-related macular degeneration
• Choroidal rupture or angioid streaks may be mistaken for lacquer cracks
• Retinal pigment epithelial changes from previous central serous chorioretinopathy
• Ocular histoplasmosis
• Pattern dystrophies (examples: reticular dystrophy, Doyne honeycomb retinal dystrophy)

Other associated systemic disorders.[23][24]

• Developmental delay
• Prematurity
• Marfans syndrome
• Stickler syndrome
• Ehlers-Danlos syndrome
• Homocystinuria
• Down syndrome
• Noonan syndrome

Pertinent Studies and Ongoing Trials

RADIANCE (A Randomized Controlled Study of Ranibizumab in Patients with Choroidal Neovascularization (CNV) Secondary to Pathologic Myopia) (n=277)

A multi-center, randomized controlled trial compared intravitreal Ranibizumab 0.5mg to Verteporfin photodynamic therapy to treat myopic CNV. The ranibizumab treatment group experienced a superior visual gain (14 letters vs. 9 letters) at 12 months. Patients received a median of 2 treatments during the 12 month study period as guided by disease activity.[19]

MYRROR study (Intravitreal Aflibercept Injection in Patients with Myopic Choroidal Neovascularization) (n=122)

A multi-center, randomized control trial compared intravitreal Aflibercept 0.5mg versus sham injection to treat myopic CNV. Additional injections were administered if there were signs of CNV activity during monthly visits. At week 24, the treatment group experienced superior visual gains (+12 letters vs. -2 letters). Patients in the treatment group received a median of 2 injections in weeks 0–8 and 0 injections in weeks 8 to 32.[20]

Both trials demonstrated that anti-VEGF therapy was effective for the treatment of myopic CNV, with good visual and anatomic benefits achieved with a limited number of injections.

Treatment Planning

The treatment regimen for a myopic choroidal neovascular membrane typically consists of intravitreal anti-VEGF injections.   Often, one or two treatments spaced approximately four weeks apart are given, followed by monitoring and further treatment as needed if signs of choroidal neovascular activity such as subretinal fluid, hemorrhage, or leakage.

Typical Anti-VEGF agents and dosing:

• Bevacuzimab 1.25mg/0.05ml
• Aflibercept 2mg/0.05ml
• Ranibizumab 0.5mg/0.05ml

Prognosis

Pathologic myopia is a significant cause of vision loss worldwide. The prevalence of visual impairment secondary to pathological myopia reaches as high as 0.5% in European studies and 1.4% in Asian studies.[10] Long-term follow-up studies of patients diagnosed with myopic CNV report a mean decline in visual acuity, even despite adequate disease control on anti-VEGF therapy.[25]

Complications

Patients with pathological myopia may experience a marked drop in visual acuity secondary to a subretinal hemorrhage or myopic choroidal neovascular membrane. Despite prompt therapy, they can develop scarring and atrophy in the macula that results in a permanent central scotoma. They also face an increased risk of early cataract formation, glaucoma, and retinal detachments, which can also lead to visual impairment.[26]

Deterrence and Patient Education

Patients should be advised to attend their regular eye appointments to ensure their disease remains optimally controlled on the available treatments. Any sudden changes to vision, including metamorphopsia, scotoma, flashes, floaters, or blurry vision, should prompt an urgent assessment by an eye care professional. Patients should be advised to check each eye with an Amsler grid regularly.

Enhancing Healthcare Team Outcomes

Despite the lack of formal guidelines, a collaborative care approach towards myopia prevention, detection, and management is required. Given the rising prevalence of myopia, which develops from childhood, public health needs to advocate for policies that encourage outdoor activity. Screening for myopia in schools or other forums requires a team of individuals such as trained technicians or nurses and a system in place for referral to an eye care provider for evaluation. Ophthalmologists optometrists manage treatment decisions such as the initiation of pharmacological or optical therapy to halt myopic progression.

Additionally, optometrists and ophthalmologists play an important role in screening for pathological myopia and its associated complications. Collaboration between glaucoma, vitreoretinal and medical retinal specialists ensures patients receive specialized care when necessary. Occupational therapists and optometrists specializing in low vision play an important role in visual rehabilitation, helping individuals maintain an independent living and maximize their vision when it is limited due to their disease.