Myopic Choroidal Neovascularization

Key points of this disease

• Myopic choroidal neovascularization (myopic CNV) is a choroid-derived new blood vessel that develops in the macula of eyes with pathologic myopia. Internationally, the term is shifting from CNV to MNV (myopic neovascularization). ⁶⁾
• It occurs in 5–11% of eyes with high myopia and is the leading cause of choroidal neovascularization in individuals aged 50 years or younger.
• Main symptoms include metamorphopsia, central scotoma, and decreased visual acuity. Because it is type 2 CNV, subjective symptoms appear early and progress rapidly.
• Without treatment, 89% of eyes have a corrected visual acuity of 0.1 or worse at 5 years, indicating a poor prognosis.
• First-line treatment is intravitreal injection of anti-VEGF drugs, with a standard regimen of one injection followed by retreatment as needed (1+PRN). ^{1), 6)}
• Fluorescein angiography (FA) is the most important diagnostic tool and is essential for differentiating from simple macular hemorrhage. ⁶⁾
• In the long term, enlargement of myopic MNV-related macular atrophy determines visual prognosis.

1. What is myopic choroidal neovascularization?

Myopic choroidal neovascularization (myopic CNV) is a choroid-derived new blood vessel that develops in the posterior pole of eyes with pathologic myopia. In recent years, the term “myopic MNV (myopic neovascularization)” has been used internationally to include not only choroid-derived but also retinal vessel-derived new vessels. ⁶⁾

It is the second most common cause of choroidal neovascularization after age-related macular degeneration and the leading cause in individuals aged 50 years or younger. It occurs in about 10% of all patients with pathologic myopia. ⁷⁾

High myopia is defined as a spherical equivalent of −6.0 D or less, or an axial length of 26.5 mm or more. Pathologic myopia is defined as eyes with atrophic changes at least as severe as diffuse atrophy in the fundus, or with posterior staphyloma (META-PM classification, 2015). ¹⁰⁾

Myopic MNV is almost always type 2 CNV (CNV located above the RPE) according to the Gass classification. It is often relatively small and exudative changes are usually mild.

Epidemiology

• Myopic MNV occurs in 5–11% of eyes with high myopia
• Over 8 years of follow-up, about 6% of patients with pathologic myopia without a history of MNV develop it
• In patients with a history of MNV in one eye, approximately 35% develop it in the fellow eye.
• In patients under 50 years of age, about 60% of MNV cases are myopic MNV⁷⁾.
• Pathologic myopia accounts for 13% of visual impairment with corrected visual acuity of 0.1 or less, and is the second leading cause of blindness after glaucoma.

Q At what age does myopic choroidal neovascularization typically develop?

A

Unlike age-related macular degeneration, myopic CNV can develop from a young age (teens). It is the most common cause of choroidal neovascularization in individuals aged 50 years or younger, and is an important disease that impairs central vision in both eyes during the working-age years. Early detection and treatment greatly influence prognosis.

2. Main Symptoms and Clinical Findings

OCTA image of myopic choroidal neovascularization

Sawai Y, et al. Usefulness of Denoising Process to Depict Myopic Choroidal Neovascularisation Using a Single Optical Coherence Tomography Angiography Image. Sci Rep. 2020. Figure 3. PMCID: PMC7148361. License: CC BY.

Representative image of the right eye of a 76-year-old woman with myopic choroidal neovascularization, showing the foreground within the yellow line and the background within the red line used to calculate CNR. This corresponds to the choroidal neovascularization discussed in the section “2. Main Symptoms and Clinical Findings.”

Subjective Symptoms

When myopic MNV involves the fovea, the following symptoms occur. Because it is type 2 CNV, exudation directly affects the outer retina, causing symptoms to appear early and progress rapidly. ⁶⁾

• Metamorphopsia: Straight lines appear distorted. New onset of metamorphopsia in a myopic patient is an important sign suggestive of myopic MNV. In cases complicated by myopic traction maculopathy, worsening of distortion may be difficult to notice. ⁶⁾
• Central scotoma: A dark spot appears in the center of the visual field.
• Visual acuity loss: Progresses rapidly when the lesion extends to the fovea. Even if the CNV regresses, if a scar remains at the fovea, irreversible visual loss occurs.

If located outside the macular area, it may be asymptomatic. Careful attention to the patient’s subjective symptoms is important. ⁶⁾

Clinical Findings

Myopic MNV is classified into three stages: active, scar, and atrophic.

Active stage

Gray-white subretinal lesion: Appears as a small lesion with pigmented borders. Smaller than MNV in age-related macular degeneration. ⁶⁾

Subretinal hemorrhage: Often seen around the CNV.

OCT findings: Dome-shaped hyperreflective elevation above the RPE. May be accompanied by subretinal fluid, subretinal hemorrhage, cystoid macular edema, or fibrin exudation, but serous changes are not prominent. ⁶⁾

Scar and atrophic stages

Fuchs spot: After MNV regression, a scar lesion with pigmentation forms due to hyperplasia of the RPE and basement membrane.

Myopic MNV-related macular atrophy: Expands relatively rapidly over the long term, leading to severe visual impairment. Observed as enlargement of Bruch’s membrane rupture and atrophy of the pigment epithelium, choriocapillaris, and outer retina. Corrected visual acuity ≤0.1 in 88.9% after 5 years and 96.3% after 10 years. ¹²⁾

On OCT angiography, the active stage shows a “lace-like network, broad anastomoses, and a low-intensity halo around the lesion,” while the quiescent stage shows “long linear mature vessels and rare anastomoses (dead tree appearance).” Internal blood flow is frequently maintained even outside the active stage (active 100%, scar ~80%, atrophic ~90%). However, OCTA is not suitable for assessing MNV activity. ⁶⁾

Differential diagnosis from age-related macular degeneration

Myopic MNV differs from age-related macular degeneration in the following ways: exudative changes are mild, and drusen or RPE detachment are absent. Most are type 2 CNV (classic CNV). It occurs predominantly in younger individuals, and the number of required anti-VEGF injections is generally lower.

3. Causes and risk factors

The development of myopic MNV is thought to involve two mechanisms: mechanical rupture of Bruch’s membrane and choroidal circulatory disturbance.

Pathogenesis

Progressive elongation of the axial length leads to stretching and thinning of the choroid and retina.

• Bruch’s membrane ruptures (lacquer cracks): The mechanical rupture site serves as a scaffold for connective tissue with MNV.
• Choroidal circulatory disturbance: Occlusion and loss of the choriocapillaris promote VEGF production.
• Patchy atrophy and lacquer cracks are predictors of MNV development ⁷⁾.

Risk Factors

• Localized chorioretinal atrophy: Especially atrophy within 1 disc diameter around the fovea.
• Lacquer cracks: Linear cracks in Bruch’s membrane. Odds ratio for CNV development: 2.56.
• Dome-shaped macula (DSM): High odds ratio of 4.95 for CNV development ⁵⁾.
• Posterior staphyloma: High myopia itself is a risk factor.
• Long axial length: Risk factor for progression of myopic maculopathy.
• Female: Prevalence of myopic chorioretinal atrophy lesions is 3.29 times higher (odds ratio).

Prevention and Daily Care

• If you have high myopia, have regular eye examinations. Especially if you notice metamorphopsia (distorted vision) or scotomas, see an ophthalmologist immediately.
• If you have a history of myopic MNV in one eye, the fellow eye may also develop it, so perform self-checks using an Amsler chart, etc.

Q Does high myopia always lead to choroidal neovascularization?

A

Not all highly myopic eyes develop myopic MNV. The incidence is about 5–11%, and the risk is particularly high in eyes with lacquer cracks or patchy atrophy. ⁷⁾ Regular eye examinations are important for early detection.

4. Diagnosis and Examination Methods

Diagnosis of myopic MNV requires confirmation of fundus changes associated with pathologic myopia and the presence of MNV. ⁶⁾ Differentiation from simple macular hemorrhage is most important, and anti-VEGF therapy is not recommended for cases where MNV cannot be confirmed. ⁶⁾

Fluorescein Fundus Angiography (FA)

This is the most emphasized examination in the guidelines. ⁶⁾

• Myopic MNV shows clear hyperfluorescence from the early phase of FA, and active MNV exhibits dye leakage from the mid to late phase.
• It can detect lesions that are unclear on ophthalmoscopy or OCT.
• In simple macular hemorrhage, only fluorescence blockage (hypofluorescence) is observed without hyperfluorescence → decisive for differentiation.
• If diagnosis is uncertain, FA should be actively performed. ⁶⁾

Optical Coherence Tomography (OCT)

• Active phase: Dome-shaped hyperreflective elevation on the RPE, with surrounding subretinal fluid and fibrin exudation. ⁶⁾
• Scar phase: Hyperreflective line of encapsulation by the RPE. The clarity of encapsulation is very useful for assessing MNV activity. ⁶⁾
• Recurrence: The line becomes unclear (comparison with previous OCT images is important). ⁶⁾
• Differentiation from simple macular hemorrhage: On OCT, it is observed as hyperreflectivity along the Henle fiber layer. ⁶⁾
• If differentiation is difficult with OCT alone, FA is essential. ⁶⁾

OCT Angiography (OCTA)

• Non-invasively evaluates blood flow presence ⁶⁾
• Useful for identifying MNV (differentiation from simple macular hemorrhage) ⁶⁾
• Reported sensitivity 90.48%, specificity 93.75% ³⁾
• Angio-B mode enables detection of early MNV that is difficult to detect with structural OCT ³⁾
• Not suitable for activity assessment (because blood flow signals may persist in scar/atrophic stages) ^{6), 14)}

IA (Indocyanine Green Angiography)

• Myopic MNV does not always show hyperfluorescence on IA ⁶⁾
• FA is preferred for assessing MNV activity ⁶⁾
• High detection performance for lacquer cracks, appearing as linear hypofluorescence in late-phase IA ⁶⁾

FAF (Fundus Autofluorescence)

• Macular atrophy is clearly visualized as hypofluorescence, making FAF useful for diagnosis and assessment of enlargement ⁶⁾
• Recommended for follow-up after MNV stabilization ⁶⁾

Differential Diagnosis

Diseases that require differentiation from myopic MNV are listed below.

Differential Disease	Key Points for Differentiation
Simple macular hemorrhage	No fluorescein leakage on FA (only fluorescence blockage). OCT shows hyperreflectivity along the Henle fiber layer. Hemorrhage resolves spontaneously within 2–3 months 6), 15)
Age-related macular degeneration	Associated with drusen and RPE detachment. MNV is large with prominent exudative changes
Punctate inner choroidopathy (PIC)	Common in young myopic women. Multiple small (<500 μm), well-defined yellowish-white lesions at the posterior pole. Choroidal thickening due to inflammation 6)
Multifocal choroiditis (MFC)	Related disease to PIC 6)
MNV associated with dome-shaped macula	OCT shows inward convex protrusion of the macula. Exudative changes may occur even without MNV 6)
Tilted disc syndrome (inferior staphyloma)	MNV may develop at the edge of inferior staphyloma 6)

Q What is the difference between simple macular hemorrhage and myopic choroidal neovascularization?

A

Simple macular hemorrhage is caused by damage to the choriocapillaris during lacquer crack formation, resolves spontaneously within 2–3 months, and does not require treatment. On OCT, it appears as hyperreflectivity along the Henle fiber layer. In contrast, myopic MNV is hemorrhage associated with MNV and shows hyperfluorescence (fluorescein leakage) on FA, allowing differentiation. If differentiation is difficult with OCT alone, FA examination is essential. ⁶⁾

5. Standard treatment

Intravitreal injection of anti-VEGF agents (first-line)

This is the only treatment whose efficacy has been proven in multicenter prospective randomized controlled trials. ⁶⁾

Approved drugs in Japan as of August 2024: ranibizumab (Lucentis®) and its biosimilars, aflibercept (Eylea®). ⁶⁾

In a network meta-analysis by Glachs et al. (2024) of 34 studies (2,098 eyes), anti-VEGF agents showed visual acuity improvement of +14.1 letters (95% CI 10.8–17.4) compared to no treatment and +12.1 letters (95% CI 8.3–15.8) compared to PDT within 6 months (both p<0.0001). ¹⁾

Dosing regimen:

• Standard: one initial dose followed by PRN (1+PRN) ^{6), 11)}
• No significant difference in visual improvement compared to 3+PRN. The 1+PRN group had fewer injections (1.8 vs. 3.2 at 12 months) ¹⁾

Cheung 2017 International Consensus treatment principles: ¹¹⁾

1. Initiate anti-VEGF therapy promptly for myopic MNV
2. Consider PDT if anti-VEGF therapy is not possible (similar visual prognosis cannot be expected)
3. One initial dose followed by PRN
4. Consider retreatment if OCT shows subretinal fluid, visual decline, or FA shows leakage
5. Extend interval up to 3 months once MNV is stable ¹¹⁾

Key clinical trials:

• MYRROR trial: Multicenter RCT of aflibercept, demonstrating significant visual improvement. ⁸⁾
• RADIANCE trial: Multicenter RCT of ranibizumab. Demonstrated efficacy. ⁹⁾

Comparison between drugs:

No significant difference in visual improvement among bevacizumab, ranibizumab, and aflibercept. ¹⁾ Aflibercept shows greater reduction in central retinal thickness, but no difference in visual outcome. ¹⁾

Other treatments

• Photodynamic therapy (PDT): Inferior visual improvement compared to anti-VEGF drugs. ¹⁾ Possible worsening of macular atrophy in the long term. Not covered by insurance. ⁶⁾
• Intravitreal triamcinolone acetonide: Inferior to anti-VEGF drugs, with risks of increased intraocular pressure and cataract progression. ¹⁾
• Laser photocoagulation: May induce MNV recurrence due to the run-off phenomenon. Currently not recommended.

Follow-up

• For active MNV, perform OCT and fundus examination every 1–3 months. ⁶⁾
• After MNV stabilization, follow up at intervals of several months to 1 year. ⁶⁾
• Recurrence detection is primarily based on OCT. If MNV enlargement or new MNV is suspected, perform OCTA. ⁶⁾
• FA is useful for activity assessment but is invasive; consider examination intervals and systemic condition. ⁶⁾
• FAF is useful for evaluating macular atrophy. ⁶⁾
• In young patients and those with small MNV, scar formation is minimal and prognosis is good. Early active intervention as soon as possible after onset is important. ⁶⁾

Precautions in treatment

• Myopic MNV often resolves with a single injection, but recurrence is possible. Even if encapsulation is observed, recurrence can occur, so long-term OCT follow-up is necessary. ⁶⁾
• When combined with myopic traction maculopathy (macular retinoschisis), anti-VEGF injections may worsen retinal detachment. ²⁾
• Rare complications of macular hole development or enlargement after anti-VEGF injection have been reported. ⁴⁾
• In some cases, macular atrophy progresses over the long term, leading to vision loss. Regular assessment of atrophy using FAF is important.

Q How many injections are needed for treatment of myopic choroidal neovascularization?

A

The standard regimen is one injection followed by retreatment as needed (1+PRN), with an average of 1.8 injections over 12 months reported. ¹⁾ The number of required injections is generally lower than for age-related macular degeneration. However, long-term follow-up for recurrence and atrophy progression is essential, and early retreatment is recommended. ⁶⁾

6. Pathophysiology and Detailed Pathogenesis

Bruch’s Membrane Rupture and Wound Healing Response

Choroidal atrophy and decreased elastic fibers in Bruch’s membrane due to axial elongation cause mechanical rupture of Bruch’s membrane, leading to lacquer cracks. Using these rupture sites as a scaffold, connective tissue with MNV proliferates under the retina as a wound healing response. Patchy atrophy and lacquer cracks are predictors of MNV development. ⁷⁾

Choroidal Circulation Disorder and VEGF

In pathologic myopia, the choriocapillaris and vascular layers are almost absent, and only large choroidal vessels may remain. Studies using EDI-OCT have reported that the choroid is significantly thinner in highly myopic eyes with MNV. Circulatory disturbance in the thinned choroidal tissue promotes VEGF production, leading to the formation of abnormal vascular networks.

CNV-Derived Vessels (Short Posterior Ciliary Arteries)

Using swept-source OCT and ICGA, findings of short posterior ciliary arteries penetrating the sclera near myopic MNV and adjacent to the MNV were confirmed in 75.0% of cases. Cases where vessels derived from the short posterior ciliary arteries are thought to perfuse the MNV are frequent: 100% in the active stage, 87.9% in the scar stage, and 73.8% in the atrophic stage.

Combination with Myopic Traction Maculopathy

The combination of myopic MNV and myopic foveoschisis (MF) is rare but has important clinical significance.

Sayanagi et al. (2023) reported three cases of MF associated with myopic MNV. ²⁾ In all cases, macular retinal detachment worsened during follow-up. It has been suggested that subretinal fluid from MNV may disrupt the centripetal and centrifugal traction balance, promoting the progression of MF.

Pereira et al. (2023) reported a case in which MNV occurring in a pathologic myopic eye with myopic foveoschisis caused a full-thickness macular hole. ⁴⁾ It is inferred that mechanical elevation due to MNV exudation applied stress to the Müller cells of the weakened fovea, leading to hole formation.

7. Latest Research and Future Perspectives (Investigational Reports)

For Patients: Please Read Carefully

The following content is currently under investigation or in clinical trials and is not standard treatment available at general hospitals. It is reference information for professionals regarding future medical developments.

Long-Term Natural History of Myopic Maculopathy

Carlà et al. (2025) reported in a long-term study of a European cohort of 1,228 eyes that 57% of myopic maculopathy progressed during follow-up of more than 10 years. ⁵⁾ 47% of eyes with patchy atrophy progressed to macular atrophy (OR 4.21), and active MNV developed in 15% of eyes at a mean of 4.5 years. MNV development was significantly correlated with visual acuity decline (p=0.001) and progression to macular atrophy (OR 5.81).

Long-Term Challenges of Anti-VEGF Therapy

Although anti-VEGF therapy provides good short-term visual improvement, long-term outcomes over 5 years are inferior to short-term results. In the natural untreated course, 89% at 5 years and 96% at 10 years have decimal visual acuity of 0.1 or worse. ¹²⁾ A 5-year study of ranibizumab reported utility in maintaining vision. ¹³⁾ Developing treatments to suppress the progression of atrophy is a future challenge.

Potential for Early Diagnosis with OCTA

OCT-A Angio-B mode may detect early MNV that is difficult to detect with structural OCT or fluorescein angiography. ³⁾ As a non-invasive and highly sensitive examination method, its application to screening for high myopia is expected.

8. References

1. Glachs L, Embacher S, Berghold A, et al. Treatment of myopic choroidal neovascularization: a network meta-analysis and review. Graefes Arch Clin Exp Ophthalmol. 2024;262:1693-1722.
2. Sayanagi K, Hara C, Fukushima Y, et al. Three cases of macular retinal detachment exacerbated during follow-up with myopic foveoschisis around myopic choroidal neovascularization. Am J Ophthalmol Case Rep. 2023;32:101899.
3. Rico S, Sher I, Lavinkfy F, et al. Optical coherence tomography Angio-B mode for early detection of myopic choroidal neovascularization and treatment with Bevacizumab. Am J Ophthalmol Case Rep. 2024;34:102041.
4. Pereira A, Ballios BG, Sarraf D, Yan P. Full-thickness macular hole due to choroidal neovascularization in the setting of pathologic myopia. J VitreoRetinal Dis. 2023;7(1):65-69.
5. Carlà MM, Boselli F, Giannuzzi F, et al. Longitudinal Progression of Myopic Maculopathy in a Long-Term Follow-Up of a European Cohort: Imaging Features and Visual Outcomes. Ophthalmol Retina. 2025;9(8):774-786. doi:10.1016/j.oret.2025.02.015. PMID:40010496.
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8. Ikuno Y, Ohno-Matsui K, Wong TY, et al; MYRROR Investigators. Intravitreal aflibercept injection in patients with myopic choroidal neovascularization: the MYRROR Study. Ophthalmology. 2015;122:1220-1227.
9. Wolf S, Balciuniene VJ, Laganovska G, et al; RADIANCE Study Group. RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology. 2014;121:682-692.
10. Ohno-Matsui K, Kawasaki R, Jonas JB, et al; META-PM Study Group. International photographic classification and grading system for myopic maculopathy. Am J Ophthalmol. 2015;159:877-883.
11. Cheung CMG, Arnold JJ, Holz FG, et al. Myopic choroidal neovascularization: review, guidance, and consensus statement on management. Ophthalmology. 2017;124:1690-1711.
12. Yoshida T, Ohno-Matsui K, Yasuzumi K, et al. Myopic choroidal neovascularization: a 10-year follow-up. Ophthalmology. 2003;110:1297-1305.
13. Onishi Y, Yokoi T, Kasahara K, et al. Five-year outcomes of intravitreal ranibizumab for choroidal neovascularization in patients with pathologic myopia. Retina. 2019;39:1289-1298.
14. Miyata M, Ooto S, Hata M, et al. Detection of myopic choroidal neovascularization using optical coherence tomography angiography. Am J Ophthalmol. 2016;165:108-114.
15. Goto S, Sayanagi K, Ikuno Y, et al. Comparison of visual prognosis between natural course of simple hemorrhage and choroidal neovascularization treated with intravitreal bevacizumab in highly myopic eyes: a 1-year follow-up. Retina. 2015;35:429-434.