RyR1 Structural Alterations Explain Statin-Associated Muscle Dysfunction
December 16, 2025
Background
Macular Telangiectasia Type 2 (MacTel) is a gradually progressing condition that affects the macula. Initially thought to be primarily a vascular disorder, recent studies indicate that it may have a neurodegenerative origin, particularly involving Muller cells. In advanced stages, retinal pigment epithelium (RPE) hyperplasia and subretinal neovascularization (SNV) are major contributors to significant vision loss.
Epidemiology
Macular Telangiectasia Type 2 (MacTel) is a bilateral, asymmetric condition that primarily affects individuals over the age of 40, with a higher prevalence in women. The Beaver Dam Eye Study found a prevalence of 0.1% in 4,790 people aged 43 to 86 years, while the Melbourne Collaborative Cohort reported a much lower prevalence of 0.0045% in 22,415 participants. The condition occurs globally with no significant racial predisposition.
Anatomy
Pathophysiology
Macular Telangiectasia Type 2 (MacTel Type 2) is a rare, progressive retinal condition that primarily affects the macula, the central part of the retina responsible for sharp, detailed vision. The pathophysiology of MacTel Type 2 involves abnormalities in the retinal vasculature, particularly in the capillaries of the macula. It is characterized by the formation of abnormal blood vessels, or telangiectatic vessels, that leak fluid and cause retinal damage. These vessels are often prone to dilation and leakage, leading to retinal edema, hemorrhages, and eventually macular atrophy. Over time, the retinal pigment epithelium (RPE) may become damaged, which disrupts the integrity of the outer retina and the blood-retina barrier. This leads to progressive vision loss, initially affecting central vision. The exact cause of the condition remains unclear, though genetic factors, including mutations in the EFEMP1 gene, have been implicated, and environmental factors may play a role in its progression.
Etiology
The etiology of Macular Telangiectasia Type 2 (MacTel Type 2) is not fully understood, but it is believed to have a genetic component, with mutations in the EFEMP1 gene being strongly associated with the condition. Environmental factors, such as age, may also contribute to its development.
Genetics
Prognostic Factors
Prognostic factors include the extent of macular involvement, the degree of retinal vascular leakage, and the presence of retinal atrophy. Early-stage disease, particularly when confined to one eye, tends to have a better prognosis, while advanced disease with significant retinal damage and atrophy can lead to more severe vision loss. Regular monitoring and early intervention are key to managing the condition and slowing its progression.
Clinical History
Age group
Macular Telangiectasia Type 2 (MacTel Type 2) typically affects individuals in middle to late adulthood, usually between the ages of 50 and 70 years. It is relatively rare in younger populations, and its prevalence increases with age. The condition is more commonly seen in individuals of European descent.
Physical Examination
Visual Acuity
Fundoscopy/Retinal Examination
Telangiectatic Vessels
Macular Edema
Pigmentary Changes
Cystoid Macular Edema
Retinal Hemorrhages
Amsler Grid Test
Fluorescein Angiography
OCT (Optical Coherence Tomography)
Age group
Associated comorbidity
Diabetes
Other Retinal Conditions
Familial Tendencies
Smoking
Dietary Factors
Associated activity
Acuity of presentation
The acuity of presentation in Macular Telangiectasia Type 2 (MacTel Type 2) varies, but it often develops slowly and subtly. Early symptoms typically include blurry or distorted central vision, with patients noticing difficulty reading or recognizing faces. In the initial stages, the condition may not cause significant pain or noticeable changes, leading to gradual vision loss over time. As the disease progresses, more pronounced visual impairment may occur due to macular edema, atrophy, and the formation of abnormal blood vessels. Central vision is usually the most affected, while peripheral vision often remains relatively intact.
Differential Diagnoses
Age–Related Macular Degeneration (AMD)
Diabetic Retinopathy
Myopic Maculopathy (High Myopia)
Central Serous Chorioretinopathy (CSC)
Retinal Vein Occlusion
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Observation and Monitoring:
In early stages with minimal vision loss, close monitoring with regular eye exams, fluorescein angiography, and OCT is recommended to detect progression, such as increased vascular leakage or macular atrophy.
Anti-VEGF Therapy:
Anti-VEGF agents like ranibizumab (Lucentis) or aflibercept (Eylea) are used to treat macular edema and abnormal blood vessels. Injections are given intravitreally to reduce leakage and swelling, with treatment frequency varying based on disease progression.
Laser Photocoagulation:
Focal laser therapy may be used for localized, telangiectatic vessels to coagulate abnormal blood vessels and prevent further leakage, though anti-VEGF therapy is now preferred due to better vision preservation.
Photodynamic Therapy (PDT):
For patients with subretinal neovascularization or significant leakage unresponsive to anti-VEGF therapy, PDT uses a photosensitizing drug activated by laser light to target abnormal vessels.
Steroid Injections:
Intravitreal corticosteroids may be used for persistent macular edema when anti-VEGF therapy is ineffective or contraindicated, but they carry risks of increased intraocular pressure and cataracts.
Genetic Counseling:
Genetic counseling can be useful for those with a family history of MacTel Type 2, and genetic testing may offer insights into inheritance patterns.
Low Vision Aids:
For patients with significant central vision loss, low vision aids like magnifiers, special lenses, or electronic devices can help improve daily function.
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
modification-of-environment
For individuals with significant vision loss from MacTel Type 2, environmental modifications can enhance safety and independence. This may include improving lighting, reducing glare, using high-contrast colors for better visibility, and organizing spaces to minimize obstacles. Additionally, using large-print materials, screen readers, and voice-activated devices can assist with daily tasks and improve quality of life.
Role of Anti-VEGF Agents
Role of Corticosteroids
role-of-surgical-approach-in-treating-macular-telangiectasia-type-2
Pars Plana Vitrectomy (PPV):
This procedure involves the removal of the vitreous humor, the gel-like substance inside the eye, to provide access to the macula for further treatment.
Internal Limiting Membrane (ILM) Peeling:
ILM peeling entails the removal of a thin layer of the retina to assist in closing a macular hole.
Inverted ILM Flap Technique:
This technique is utilized for challenging cases of macular holes that do not respond to ILM peeling alone, where the ILM is flipped back to help seal the hole.
Gas Tamponade:
In some instances, a gas bubble is introduced into the eye to help maintain retinal shape and promote the closure of the macular hole.
role-of-surgical-outcomes-in-mactel-2
Success Rates:
The success rate of macular hole surgery in patients with MacTel Type 2 tends to be lower compared to those with idiopathic macular holes, as the hole may not always close or could reopen post-surgery.
Factors Affecting Success:
The presence of macular atrophy and the specific characteristics of the macular hole seen on optical coherence tomography (OCT) can impact the likelihood of a successful outcome.
Potential for Improvement:
While surgery may not always fully resolve the problem, it can lead to some improvement in visual acuity and may help reduce the risk of further vision deterioration.
phases-of-management
Early Phase (Observation and Monitoring):
Active Phase (Therapeutic Intervention):
Chronic Phase (Ongoing Monitoring and Support):
Medication
Future Trends
Macular Telangiectasia Type 2 (MacTel) is a gradually progressing condition that affects the macula. Initially thought to be primarily a vascular disorder, recent studies indicate that it may have a neurodegenerative origin, particularly involving Muller cells. In advanced stages, retinal pigment epithelium (RPE) hyperplasia and subretinal neovascularization (SNV) are major contributors to significant vision loss.
Macular Telangiectasia Type 2 (MacTel) is a bilateral, asymmetric condition that primarily affects individuals over the age of 40, with a higher prevalence in women. The Beaver Dam Eye Study found a prevalence of 0.1% in 4,790 people aged 43 to 86 years, while the Melbourne Collaborative Cohort reported a much lower prevalence of 0.0045% in 22,415 participants. The condition occurs globally with no significant racial predisposition.
Macular Telangiectasia Type 2 (MacTel Type 2) is a rare, progressive retinal condition that primarily affects the macula, the central part of the retina responsible for sharp, detailed vision. The pathophysiology of MacTel Type 2 involves abnormalities in the retinal vasculature, particularly in the capillaries of the macula. It is characterized by the formation of abnormal blood vessels, or telangiectatic vessels, that leak fluid and cause retinal damage. These vessels are often prone to dilation and leakage, leading to retinal edema, hemorrhages, and eventually macular atrophy. Over time, the retinal pigment epithelium (RPE) may become damaged, which disrupts the integrity of the outer retina and the blood-retina barrier. This leads to progressive vision loss, initially affecting central vision. The exact cause of the condition remains unclear, though genetic factors, including mutations in the EFEMP1 gene, have been implicated, and environmental factors may play a role in its progression.
The etiology of Macular Telangiectasia Type 2 (MacTel Type 2) is not fully understood, but it is believed to have a genetic component, with mutations in the EFEMP1 gene being strongly associated with the condition. Environmental factors, such as age, may also contribute to its development.
Prognostic factors include the extent of macular involvement, the degree of retinal vascular leakage, and the presence of retinal atrophy. Early-stage disease, particularly when confined to one eye, tends to have a better prognosis, while advanced disease with significant retinal damage and atrophy can lead to more severe vision loss. Regular monitoring and early intervention are key to managing the condition and slowing its progression.
Age group
Macular Telangiectasia Type 2 (MacTel Type 2) typically affects individuals in middle to late adulthood, usually between the ages of 50 and 70 years. It is relatively rare in younger populations, and its prevalence increases with age. The condition is more commonly seen in individuals of European descent.
Visual Acuity
Fundoscopy/Retinal Examination
Telangiectatic Vessels
Macular Edema
Pigmentary Changes
Cystoid Macular Edema
Retinal Hemorrhages
Amsler Grid Test
Fluorescein Angiography
OCT (Optical Coherence Tomography)
Diabetes
Other Retinal Conditions
Familial Tendencies
Smoking
Dietary Factors
The acuity of presentation in Macular Telangiectasia Type 2 (MacTel Type 2) varies, but it often develops slowly and subtly. Early symptoms typically include blurry or distorted central vision, with patients noticing difficulty reading or recognizing faces. In the initial stages, the condition may not cause significant pain or noticeable changes, leading to gradual vision loss over time. As the disease progresses, more pronounced visual impairment may occur due to macular edema, atrophy, and the formation of abnormal blood vessels. Central vision is usually the most affected, while peripheral vision often remains relatively intact.
Age–Related Macular Degeneration (AMD)
Diabetic Retinopathy
Myopic Maculopathy (High Myopia)
Central Serous Chorioretinopathy (CSC)
Retinal Vein Occlusion
Observation and Monitoring:
In early stages with minimal vision loss, close monitoring with regular eye exams, fluorescein angiography, and OCT is recommended to detect progression, such as increased vascular leakage or macular atrophy.
Anti-VEGF Therapy:
Anti-VEGF agents like ranibizumab (Lucentis) or aflibercept (Eylea) are used to treat macular edema and abnormal blood vessels. Injections are given intravitreally to reduce leakage and swelling, with treatment frequency varying based on disease progression.
Laser Photocoagulation:
Focal laser therapy may be used for localized, telangiectatic vessels to coagulate abnormal blood vessels and prevent further leakage, though anti-VEGF therapy is now preferred due to better vision preservation.
Photodynamic Therapy (PDT):
For patients with subretinal neovascularization or significant leakage unresponsive to anti-VEGF therapy, PDT uses a photosensitizing drug activated by laser light to target abnormal vessels.
Steroid Injections:
Intravitreal corticosteroids may be used for persistent macular edema when anti-VEGF therapy is ineffective or contraindicated, but they carry risks of increased intraocular pressure and cataracts.
Genetic Counseling:
Genetic counseling can be useful for those with a family history of MacTel Type 2, and genetic testing may offer insights into inheritance patterns.
Low Vision Aids:
For patients with significant central vision loss, low vision aids like magnifiers, special lenses, or electronic devices can help improve daily function.
Ophthalmology
For individuals with significant vision loss from MacTel Type 2, environmental modifications can enhance safety and independence. This may include improving lighting, reducing glare, using high-contrast colors for better visibility, and organizing spaces to minimize obstacles. Additionally, using large-print materials, screen readers, and voice-activated devices can assist with daily tasks and improve quality of life.
Ophthalmology
Ophthalmology
Ophthalmology
Pars Plana Vitrectomy (PPV):
This procedure involves the removal of the vitreous humor, the gel-like substance inside the eye, to provide access to the macula for further treatment.
Internal Limiting Membrane (ILM) Peeling:
ILM peeling entails the removal of a thin layer of the retina to assist in closing a macular hole.
Inverted ILM Flap Technique:
This technique is utilized for challenging cases of macular holes that do not respond to ILM peeling alone, where the ILM is flipped back to help seal the hole.
Gas Tamponade:
In some instances, a gas bubble is introduced into the eye to help maintain retinal shape and promote the closure of the macular hole.
Ophthalmology
Success Rates:
The success rate of macular hole surgery in patients with MacTel Type 2 tends to be lower compared to those with idiopathic macular holes, as the hole may not always close or could reopen post-surgery.
Factors Affecting Success:
The presence of macular atrophy and the specific characteristics of the macular hole seen on optical coherence tomography (OCT) can impact the likelihood of a successful outcome.
Potential for Improvement:
While surgery may not always fully resolve the problem, it can lead to some improvement in visual acuity and may help reduce the risk of further vision deterioration.
Ophthalmology
Early Phase (Observation and Monitoring):
Active Phase (Therapeutic Intervention):
Chronic Phase (Ongoing Monitoring and Support):
Macular Telangiectasia Type 2 (MacTel) is a gradually progressing condition that affects the macula. Initially thought to be primarily a vascular disorder, recent studies indicate that it may have a neurodegenerative origin, particularly involving Muller cells. In advanced stages, retinal pigment epithelium (RPE) hyperplasia and subretinal neovascularization (SNV) are major contributors to significant vision loss.
Macular Telangiectasia Type 2 (MacTel) is a bilateral, asymmetric condition that primarily affects individuals over the age of 40, with a higher prevalence in women. The Beaver Dam Eye Study found a prevalence of 0.1% in 4,790 people aged 43 to 86 years, while the Melbourne Collaborative Cohort reported a much lower prevalence of 0.0045% in 22,415 participants. The condition occurs globally with no significant racial predisposition.
Macular Telangiectasia Type 2 (MacTel Type 2) is a rare, progressive retinal condition that primarily affects the macula, the central part of the retina responsible for sharp, detailed vision. The pathophysiology of MacTel Type 2 involves abnormalities in the retinal vasculature, particularly in the capillaries of the macula. It is characterized by the formation of abnormal blood vessels, or telangiectatic vessels, that leak fluid and cause retinal damage. These vessels are often prone to dilation and leakage, leading to retinal edema, hemorrhages, and eventually macular atrophy. Over time, the retinal pigment epithelium (RPE) may become damaged, which disrupts the integrity of the outer retina and the blood-retina barrier. This leads to progressive vision loss, initially affecting central vision. The exact cause of the condition remains unclear, though genetic factors, including mutations in the EFEMP1 gene, have been implicated, and environmental factors may play a role in its progression.
The etiology of Macular Telangiectasia Type 2 (MacTel Type 2) is not fully understood, but it is believed to have a genetic component, with mutations in the EFEMP1 gene being strongly associated with the condition. Environmental factors, such as age, may also contribute to its development.
Prognostic factors include the extent of macular involvement, the degree of retinal vascular leakage, and the presence of retinal atrophy. Early-stage disease, particularly when confined to one eye, tends to have a better prognosis, while advanced disease with significant retinal damage and atrophy can lead to more severe vision loss. Regular monitoring and early intervention are key to managing the condition and slowing its progression.
Age group
Macular Telangiectasia Type 2 (MacTel Type 2) typically affects individuals in middle to late adulthood, usually between the ages of 50 and 70 years. It is relatively rare in younger populations, and its prevalence increases with age. The condition is more commonly seen in individuals of European descent.
Visual Acuity
Fundoscopy/Retinal Examination
Telangiectatic Vessels
Macular Edema
Pigmentary Changes
Cystoid Macular Edema
Retinal Hemorrhages
Amsler Grid Test
Fluorescein Angiography
OCT (Optical Coherence Tomography)
Diabetes
Other Retinal Conditions
Familial Tendencies
Smoking
Dietary Factors
The acuity of presentation in Macular Telangiectasia Type 2 (MacTel Type 2) varies, but it often develops slowly and subtly. Early symptoms typically include blurry or distorted central vision, with patients noticing difficulty reading or recognizing faces. In the initial stages, the condition may not cause significant pain or noticeable changes, leading to gradual vision loss over time. As the disease progresses, more pronounced visual impairment may occur due to macular edema, atrophy, and the formation of abnormal blood vessels. Central vision is usually the most affected, while peripheral vision often remains relatively intact.
Age–Related Macular Degeneration (AMD)
Diabetic Retinopathy
Myopic Maculopathy (High Myopia)
Central Serous Chorioretinopathy (CSC)
Retinal Vein Occlusion
Observation and Monitoring:
In early stages with minimal vision loss, close monitoring with regular eye exams, fluorescein angiography, and OCT is recommended to detect progression, such as increased vascular leakage or macular atrophy.
Anti-VEGF Therapy:
Anti-VEGF agents like ranibizumab (Lucentis) or aflibercept (Eylea) are used to treat macular edema and abnormal blood vessels. Injections are given intravitreally to reduce leakage and swelling, with treatment frequency varying based on disease progression.
Laser Photocoagulation:
Focal laser therapy may be used for localized, telangiectatic vessels to coagulate abnormal blood vessels and prevent further leakage, though anti-VEGF therapy is now preferred due to better vision preservation.
Photodynamic Therapy (PDT):
For patients with subretinal neovascularization or significant leakage unresponsive to anti-VEGF therapy, PDT uses a photosensitizing drug activated by laser light to target abnormal vessels.
Steroid Injections:
Intravitreal corticosteroids may be used for persistent macular edema when anti-VEGF therapy is ineffective or contraindicated, but they carry risks of increased intraocular pressure and cataracts.
Genetic Counseling:
Genetic counseling can be useful for those with a family history of MacTel Type 2, and genetic testing may offer insights into inheritance patterns.
Low Vision Aids:
For patients with significant central vision loss, low vision aids like magnifiers, special lenses, or electronic devices can help improve daily function.
Ophthalmology
For individuals with significant vision loss from MacTel Type 2, environmental modifications can enhance safety and independence. This may include improving lighting, reducing glare, using high-contrast colors for better visibility, and organizing spaces to minimize obstacles. Additionally, using large-print materials, screen readers, and voice-activated devices can assist with daily tasks and improve quality of life.
Ophthalmology
Ophthalmology
Ophthalmology
Pars Plana Vitrectomy (PPV):
This procedure involves the removal of the vitreous humor, the gel-like substance inside the eye, to provide access to the macula for further treatment.
Internal Limiting Membrane (ILM) Peeling:
ILM peeling entails the removal of a thin layer of the retina to assist in closing a macular hole.
Inverted ILM Flap Technique:
This technique is utilized for challenging cases of macular holes that do not respond to ILM peeling alone, where the ILM is flipped back to help seal the hole.
Gas Tamponade:
In some instances, a gas bubble is introduced into the eye to help maintain retinal shape and promote the closure of the macular hole.
Ophthalmology
Success Rates:
The success rate of macular hole surgery in patients with MacTel Type 2 tends to be lower compared to those with idiopathic macular holes, as the hole may not always close or could reopen post-surgery.
Factors Affecting Success:
The presence of macular atrophy and the specific characteristics of the macular hole seen on optical coherence tomography (OCT) can impact the likelihood of a successful outcome.
Potential for Improvement:
While surgery may not always fully resolve the problem, it can lead to some improvement in visual acuity and may help reduce the risk of further vision deterioration.
Ophthalmology
Early Phase (Observation and Monitoring):
Active Phase (Therapeutic Intervention):
Chronic Phase (Ongoing Monitoring and Support):

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