加齢性黄斑変性（AMD）は、先進国の50歳以上の成人における失明原因の第1位となっており、世界中の患者数は3000万人を超えると言われています。その最大の特徴は、鮮明な画像を認識する機能を持つ黄斑が徐々に劣化することによる中心視野の喪失です。AMDは読書、運転、顔の認識、テレビを見る、階段の上り下りなど、日常生活を困難にします。
AMDは痛みを伴わず、発生は片目のみの場合と両目の場合があり、進行のスピードも様々です。
AMDが緩やかに進行する場合、初期の段階では脳が歪みを修正するため、症状に気付きにくい場合があります。一方、急速に進行する場合にはすぐに失明へと至る可能性もあります。進行のスピードに関わらず、AMDを治療せずに放置すると、失明の原因となる進行期のAMDに移行する可能性があります。

AMDには委縮性と滲出性の2タイプがあります。

委縮性AMDは一番多く見られるタイプで、初期・中期の委縮性AMDがAMD全患者の90%を占めると言われています。疾患の初期段階では、ドルーゼンという黄白色斑が眼底に蓄積し、それに伴い黄斑の機能が低下します。ドルーゼンの発生自体は加齢に伴う自然な現象とされています。委縮性AMDの初期段階では、小型のドルーゼンが多く発生するか、中型のドルーゼンがいくつか発生し視力低下は伴いません。小型のドルーゼンが増加したり、大型のドルーゼンが発生したりすると中期へと移行します。この頃になると、中心視野のゆがみや視界のぼやけ、文字を読む事が困難になるといった症状が現れます。
中間期の委縮性AMDは進行期に移行するか、場合によっては滲出性AMDへと移行します。委縮性AMDの進行期においては、ドルーゼンの数や大きさの増加に伴い、地図状委縮と呼ばれる黄斑の光検出器や周辺組織の劣化が起こります。地図状委縮は中心視野の暗点の発生やコントラスト感度の低下、明るい場所から暗い場所へと移動した際の調整能力の低下、小さな文字を読むことができなくなるなど、より重大で不可逆的な視力低下を起こします。
委縮型AMDは片目で発生する場合と両目に発生する場合があります。片目で発生した場合、健康な方の目が疾患を抱える目の機能低下を補うため、より発見が困難になります。そのため、定期的に両目の視力検査を行う事が特に大切となります。

滲出性AMDは加齢黄斑変性の中で最も深刻で重大な状態であり、疾患の進行期のみに発生します。滲出性AMDはすべて委縮性AMDから移行して発生しますが、実際に滲出性AMDへと移行する委縮性AMD患者は全体の10%から15%程度に限られます。滲出性AMDは、黄斑下部における毛細血管の異常な発生と漏れに特徴付けられます。
ゆるやかに段階を踏んで進行する委縮型AMDとは異なり、滲出性AMDは黄斑を急速に損傷し、短期間のうちに中心視野が失われることがあります。したがって、滲出性AMDへと進行する危険性のある患者は定期健診を受ける事が非常に重要です。

滲出性AMDの場合、血管新生と呼ばれるプロセスによって、黄斑下部の毛細血管が異常に成長します。この異常な血管から体液や血液が漏出すると、黄斑下部に水膨れ状のポケットが発生し、視界のゆがみやまっすぐな線が歪んで見える原因となります。また、黄斑下部に体液が溜まる事で、中心視野のあらゆる所に暗点があらわれる様になります。

滲出性AMDを治療せずに放置すると、出血により瘢痕組織が形成され、不可逆的な視力低下を招きます。しかし、幸いな事に滲出性AMDに対する有効な治療法がいくつか存在します。これらの治療法は症状を安定させ、瘢痕組織が形成される前であれば、視力を回復させる事が出来る場合もあります。

以下はAMDの発生を促進する主な要因です。

• 加齢が一番の危険因子です。特に60歳以上の方はAMD発生のリスクが最も高く、注意が必要です。
• 近親者にAMDと診断された方がいらっしゃる場合にはAMD発生のリスクが高まります。
• すでに片目にAMDを患っている場合、もう片方の目にも発生するリスクが高まります。
• 喫煙者は非喫煙者と比べ、AMD発生のリスクが2倍から3倍高くなります。喫煙すればするほどリスクは高くなりますが、禁煙によってAMD発生のリスクを減らす事ができます。
• AMDは男性と比べ、女性に多く発生します。
• AMDはアフリカ系の人々に比べ、白人に多く発生します
• 肥満は初中期のAMDから進行期へ移行するリスクを高めます。
• コントロール不良の高血圧症はAMD発生のリスクを高めます。

リスクを減らす方法
 

• 喫煙しない
• 正常な体重を維持する
• 血圧をコントロールする
• 緑黄色野菜やフルーツが豊富な食生活はAMDのリスクを低下させます。日常的に魚を食べ、脂肪分を避ける事もリスク低下に有効です。これらの食品は抗酸化物質や異常な血管新生を自然に防ぐ成分を豊富に含んでいます。
   
  
• 運動の習慣もリスクを低下させる可能性があります。

(English) Diabetic macular edema (DME) is a form of diabetic retinopathy and a leading cause of vision loss in patients with DR.^{26, 27} It is characterized by swelling or thickening of the retina and the leaking of fluid, specifically in the macula,²⁸ a small area in the back of the eye that focuses and sharpens vision.¹⁵

Prevalence
Globally, 21 million people are estimated to live with DME.²⁰ Over 20% of people living with type 1 diabetes and 14-25% of people with type 2 diabetes (depending on their use of insulin) will develop DME within ten years.^{29, 30}

Development of DME
DME is caused when fluid accumulates in the macula. It can develop without symptoms at any of the four stages of diabetic retinopathy, though it typically occurs in the more advanced forms. It is found in almost 50% of people with proliferative retinopathy, the advanced stage of DR.¹⁵

As was described in the development of diabetic retinopathy, high levels of blood glucose in diabetes patients cause damage to retinal blood vessels. This may deprive the retina of needed oxygen (a condition called hypoxia), which prompts an increase, or upregulation, in the glycoprotein VEGF (vascular endothelial growth factor). High levels of VEGF weaken the vessel wall and increase vascular permeability, which contributes to blood vessels becoming leaky.

As the vessels leak fluid and blood into the retina and, ultimately, the macula, the macula swells and thickens, resulting in macular edema.¹⁵

Swelling of the macula reduces visual acuity,³¹ the clarity or sharpness of vision at a distance, and blurs sight. If left untreated, DME can lead to severe and even permanent vision loss. When DME is treated in its early stages, vision loss can be delayed, stopped or, in some cases, even reversed.¹³

DME: TWO TYPES

There are two types of diabetic macular edema: focal and diffuse. However, there is no clear, consistent definition for these two types, and the classification and use of these terms has been inconsistent.³² It can be helpful to distinguish between focal and diffuse forms of DME because they may have different pathological processes, which would affect prognosis and predicting treatment outcomes²⁴ for some therapies.

Focal
Focal macular edema is the most common and less severe form of DME.³² It is caused by changes in the structure of the retinal blood vessels, such as microaneurysms³³ or dilated capilleries,^{32, 34} that leak fluid into a smaller area of the macula and do not involve the center of the macula.³² Because edema is limited, visual acuity does not decrease as much as it does in the diffuse form.

Diffuse
Diffuse macular edema is a less common but more severe form of DME that can be difficult to manage.²⁴ It occurs when small capillaries in and around the macula leak fluid throughout most of the macula,³⁴ including its center.³² As a result, most of the macula is thickened and visual acuity is more greatly reduced.³² The risk of developing diffuse macular edema increases with the severity of diabetic retinopathy.²⁸

(English) A risk factor is anything that affects your chances of getting a disease. Research has focused on risk factors for diabetic retinopathy so there has been little examination of risk factors specific to DME.²⁴ However, diabetic retinopathy and DME both develop as a complication of diabetes and have similar risk factors.

Addressing the risk factors is the best way to slow or halt progression of either disease, which may occur without any changes to vision until it is too late to treat the condition. Diabetic retinopathy and DME rarely have visual symptoms in their early development and vision loss can occur very suddenly, so it is important to get regular screenings before symptoms appear.¹³

(English)

WARNING: Diabetic retinopathy & DME develop with NO symptoms!

Diabetic retinopathy develops without early symptoms or causing pain.¹⁵ Even in the advanced stages, proliferative retinopathy may not cause symptoms.¹⁵ Macular edema can develop at any stage of diabetic retinopathy without affecting vision.¹⁵ It is important not to wait for symptoms. Get tested before any issues with vision occur.

Up to 50% of diabetes patients do not get their eyes examined or are diagnosed when it is too late for treatment to be effective.⁵⁴

If blood vessels bleed into the eye, you may see blind spots in your vision. The spots may clear temporarily, but bleeding may reoccur and damage vision if the condition is left untreated. You may also experience blurry vision, or colors may look “washed out” or faded.⁵⁵ Go see an eye care professional at the first sign of any of these symptoms.

In its early stages, diabetic retinopathy can be treated and vision can be preserved.¹⁹ If you do not receive treatment, diabetic retinopathy may progress into the proliferative form. Macular edema can also develop without symptoms and, if timely treatment is not obtained, DME may result in severe vision loss.

Early detection and timely treatment can save your vision. Learn How:

What You Can Do

As a person with diabetes, regular maintenance and regulation of your condition should be an integral part of daily life. There are steps that you can take to prevent or delay vision loss, and manage your condition and treatment:⁵⁶

• Regular Screening:
  Get a comprehensive dilated eye exam at least once a year.

   

  It is recommended that people aged ten years or older with type 1 diabetes have a comprehensive eye exam within five years of the diagnosis, and that people with type 2 diabetes get a comprehensive eye exam as soon as they are diagnosed. Both type 1 and 2 diabetes patients should continue to receive subsequent eye exams on an annual basis.^15,16 Less frequent exams may be an option after successful completion of one or more normal eye exams. If diabetic retinopathy is progressing, exams may be more frequent.¹⁶
   

  Work with your eye care specialist to assess the best frequency of exams in order to manage your condition and prevent, or slow down, disease progression.

 

• Control Blood Glucose:
  HbA1c levels are a long-term measure of blood glucose control. HbA1c is a molecule that is formed when hemoglobin, a protein in red blood cells, connects to glucose.³⁷ If there is more glucose in the blood to connect with hemoglobin, then more HbA1c will form.

   

  Keep your blood glucose levels as close to normal as you can.¹ Hyperglycemia initiates many other risk factors, so controlling blood glucose can prevent other diabetic complications and slows down or even prevents the development of retinopathy.¹⁵

   

  Discuss with your doctor about how best to control blood glucose levels.

 

• Control Blood Pressure:
  Studies have demonstrated that keeping your blood pressure as close to normal as possible reduces the risk of complications in the microvascular system by roughly 33%.¹
   
  Typically, the goal is to maintain a consistent blood pressure < 130/80 or below the 90th percentile for age, sex, and height (whichever number is lower).¹⁶
   
  You can find more information on healthy blood pressure levels specific to age, sex and height at: www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.pdf

 

• Control Blood Lipids:
  Keeping your cholesterol levels as close to normal as possible reduces risk of complications.¹ High levels of total cholesterol or triglycerides can increase the risk of developing DME by two- or three-fold.⁵⁷

(English) If you have type 1 or type 2 diabetes, you should get a comprehensive eye exam at least once a year to screen for diabetic retinopathy and diabetic macular edema.
 
An ophthalmologist or optometrist who is experienced in diagnosing, managing and treating DR and DME is best suited to conduct these exams.¹⁶
 
A comprehensive eye exam typically includes a dilated eye exam, visual acuity test and tonometry. These tests can detect early signs of DR or DME, such as:¹⁵

• Retinal blood vessels that leak
• Damage or any change to the blood vessels
• Swelling or thickening of the retina

 
Types of Tests
A comprehensive eye exam includes:
 
1. Dilated Eye Exam
During a dilated eye exam, you will receive eye drops that dilate your pupils. This allows your eye specialist to see what is happening inside your eyes. Using a magnifying lens, your eye specialist will assess your retina and optic nerve to find any potential problems. If you have diabetes, it is important to receive this test at least once a year.¹⁵
 
2. Visual Acuity Test
This test uses an eye chart to measure your vision at various distances.¹⁵
 
3. Tonometry
This test measures the pressure in your eye(s) and may use numbing drops.¹⁵
 
4. Fluorescein angiogram (FA)
This test is taken when presence of DME is suspected. A certain type of dye will be injected into your arm and will pass through your blood vessels. This dye allows pictures to be taken of the retinal blood vessels so your eye care professional can detect any vessels that leak. If DME is found, work with your eye care specialist to determine the best treatment.¹⁵
 
5. Optical Coherence Tomography (OCT)
OCT is another tool that tests for DME. It is a certain type of camera that photographs and measures the thickness of your retina. It is also effective at detecting any swelling and fluid in the retina.⁵⁸ The benefit of OCT is that it is non-invasive. Also, it makes it possible to evaluate treatment response more objectively.³³
 
When to Get Tested¹⁶
 
Type 1 Diabetes
Patients with type 1 diabetes aged ten years or older should have their first comprehensive dilated eye exam within 5 years of developing diabetes.
 
Type 2 Diabetes
Patients with type 2 diabetes should have their first comprehensive dilated eye exam as soon as their diabetes is diagnosed.
 
Both type 1 and 2 diabetes patients should continue to receive subsequent eye exams on an annual basis. Less frequent exams may be an option after successful completion of one or more normal eye exams. Exams will be more frequent if retinopathy is progressing. Work with your ophthalmologist or optometrist to identify the best frequency of testing for you.
 
If you are diagnosed with severe nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, or DME, go see an eye specialist experienced in treating and managing these conditions.

(English) What Is VEGF?
The vascular endothelial growth factor (VEGF) is a glycoprotein that has been found to contribute significantly to the development of diabetic macular edema. VEGF plays an important role in many processes in the body, but excessively high levels of VEGF can have harmful effects.

VEGF & DME
Excessively high levels of VEGF have been found in retinopathy⁵⁹ and DME.⁶¹ When retinal blood vessels become weak or blocked in diabetic retinopathy, the retina cannot receive enough blood or oxygen (hypoxia) and sends signals to the body for nourishment. VEGF is then released in the retina at abnormally high levels, which increases vascular permeability. This contributes to the rupture of the blood vessel wall and consequential swelling of the vessels,^{33, 60} resulting in damaged vessels that leak³³ fluid into the central retina. As fluid accumulates in the macula, the macula swells and thickens, resulting in swelling of the macula and, ultimately, DME.
 
Research has shown that over-expression of VEGF plays a significant role in DME⁶¹ and is an important target for treating the condition.

(English)

The Angiogenesis Foundation has published a new Webinar Series on Vascular Stabilization in Retina Health and Disease to provide the vision community and clinicians treating retinal vascular eye diseases with an up to date overview of the Angiopoietin-Tie Pathway, and how this pathway is involved in retinal health and disease.

Webinar speakers include: Max Gomez, PhD, Charles Wykoff MD, PhD, David Eichenbaum, MD, and Ramin Tadayoni, MD, PhD. Watch now: https://www.scienceofang2.org/webinar