Degenerative Myopia

Etiology

Myopia is attributable to a complex interaction between genetics and the environment. Familial clustering in myopia is evident in results from 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 Marfan and Stickler syndrome, the implicated genes are involved in the extracellular matrix of the sclera. Gene studies have identified 25 different genetic loci in association with nonsyndromic 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 study results 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 socioeconomic 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 and continues to early adulthood. Most children are born hyperopic. Then, closer to the age of 5 to 8, they experience a shift in their refraction through emmetropisation. After this process, the cornea stabilizes but increases in axial length, leading 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 (see Image. Grade 3 Pathological Myopia With Diffuse Chorioretinal Atrophy).

History and Physical

A complete history should focus 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 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 and intraocular pressure and assessing pupillary reaction. Next, a dilated fundal examination should be performed on the macula, optic disc, and peripheral retina. Finally, if glaucoma is suspected, an assessment of visual fields can be requested. In 2015, a specialist panel of researchers developed a universal classification system for pathological myopia (see Table. Pathological Myopia Categories). The Proposed Classification of Myopic Maculopathy was submitted by the Meta-Analysis for Pathologic Myopia Study Group.[2] 

Table. Pathological Myopia Categories

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 10 types based on shape and location.[12] 
• Lacquer cracks are irregular yellow linear lesions in the macula. They represent mechanical linear breaks in Bruch membrane and are potential foci for choroidal neovascularisation. Newly formed lacquer cracks may be associated with bleeding.
• 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 (see Image. Dome-Shaped Maculopathy With Subretinal Fluid). Fuchs spots are pigmented gray scars corresponding to regressed myopic CNV sites.
• Myopic tractional maculopathy results from vitreoretinal traction and its manifestations 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; this 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 are more possible findings.

Evaluation

Spectral-domain optical coherence tomography (OCT) scanning is noninvasive, quick, and widely available. This scan 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 and subretinal or intraretinal fluid and also highlights the presence of macular holes, retinoschisis, or detachments. Dome-shaped maculopathy is best visualized on radial or vertical OCT slices (see Image. Dome-Shaped Maculopathy on Vertical Optical Coherence Tomography Scan).

Fluorescein angiography 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 fluorescein angiography, demonstrating early hyperfluorescence that increases in size and intensity through to the late phase. This can help differentiate between hemorrhage from a myopic CNV versus a lacquer crack, with the latter displaying blocked fluorescence instead of increasing hyperfluorescence (see Image. Fluorescein Angiogram Demonstrating Myopic Choroidal Neovascular Membrane). Other tests, such as OCT angiography, ultrasonography, magnetic resonance imaging, and Indocyanine Green Angiography, may be useful for evaluating the shape and perfusion of the retina and choroid. However, these tests are rarely used in a clinical setting.[15][16][17]

Treatment / Management

Simple myopia can be satisfactorily corrected using 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 (VEGF) intravitreal injections. Results from 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](A1)

The management of myopic tractional maculopathy remains debatable and depends on specific OCT findings.[21] Some clinicians favor a conservative approach as some cases 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 (see Image. Myopic Macular Schisis).(B2)

Differential Diagnosis

The differential diagnoses for degenerative myopia include the following:

• 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 (eg, reticular dystrophy, Doyne honeycomb retinal dystrophy)

Other associated systemic disorders include:

• Developmental delay
• Prematurity
• Marfan syndrome
• Stickler syndrome
• Ehlers-Danlos syndrome
• Homocystinuria
• Down syndrome
• Noonan syndrome [23][24]

Pertinent Studies and Ongoing Trials

The following 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:

RADIANCE

RADIANCE is a multicenter, randomized controlled study of ranibizumab in patients with secondary to pathologic myopia (n= 277). This study compared intravitreal ranibizumab 0.5 mg 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

MYRROR is a multicenter, randomized control trial of intravitreal aflibercept injection in patients with myopic CNV (n= 122). This study compared intravitreal aflibercept 0.5 mg versus placebo 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]

Treatment Planning

The treatment regimen for a myopic choroidal neovascular membrane typically consists of intravitreal anti-VEGF injections. Often, 1 or 2 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 is as follows:

• Bevacuzimab (1.25 mg/0.05 mL)
• Aflibercept (2 mg/0.05 Ll)
• Ranibizumab (0.5 mg/0.05 mL)

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%, as seen in European and 1.4% in Asian study results.[10] Long-term follow-up results from 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]