EYE DISEASE_Draft

What is Corneal Dystrophy?

Corneal dystrophy is a leading hereditary eye disease that can lead to vision impairment and blindness due to the accumulation of various types of light gray proteins in the cornea during the recovery process following corneal damage, resulting in loss of corneal transparency.

Causes

Various genes, including TGFBI(Transforming Growth Factor Beta-Induced), are known to contribute to the
development of corneal dystrophy.

Among these, five types of mutations in the TGFBI gene (R555W, R124H, R124C, R124L, R555Q) are most frequently reported. These five mutations in the TGFBI gene are the primary contributors to the development of Granular Corneal Dystrophy Type 1 (GCD1), Granular Corneal Dystrophy Type 2 (GCD2), Lattice Corneal Dystrophy Type 1 (LCD1), Reis-Bucklers Corneal Dystrophy (RBCD), and Thiel-Behnke Corneal Dystrophy (TBCD), respectively.

Symptoms

Normal Eye

Generally, corneal dystrophy tends to appear
during childhood or early adulthood, but
symptoms may also manifest in the late 30s
due to genetic or environmental differences.
Moreover, within families carrying genetic
mutations, the onset age can vary significantly.

Eye with
Corneal Dystrophy

It is important for patients with corneal
dystrophy gene mutations to undergo genetic
testing in advance because undergoing
refractive surgeries such as LASIK, LASEK, or
SMILE LASIK can rapidly exacerbate symptoms.

Five Types of TGFBI Corneal Dystrophy

: According to the IC3D classification, these five types classified as TGFBI Corneal Dystrophy
are conditions that arise from mutations in the TGFBI (Transforming Growth Factor-Beta
Induced) gene, which commonly express the keratoepithelin protein.

Granular Corneal
Dystrophy Type 1(GCD1)

Granular Corneal Dystrophy Type 1 is an autosomal dominant inherited disorder caused by the Arg555Trp mutation of the TGFBI gene located on chromosome 5q31.

Characteristics

The disease manifests in the central area of the corneal stroma's anterior layer, progressing in small particles or breadcrumb-like shapes.
Lesions typically begin in adolescence, but in some cases, they may start as early as age three. Initial symptoms often include discomfort from bright light, a phenomenon known as photophobia, usually beginning before the teenage years. The progressive disease leads to vision loss, with corneal opacity worsening with age. Recurrent corneal erosions are common, and symptoms can be more severe in homozygous individuals.
It differs slightly from the opacification pattern of Granular Corneal Dystrophy Type 2 and, unlike Type 2, does not involve ‘amyloid’ deposition.

Prevalence

The prevalence of Granular Corneal Dystrophy Type 1 is not precisely known but is frequently reported in European regions.

Causative Gene

TGFBI R555W

Granular Corneal
Dystrophy Type 2(GCD2)

Granular Corneal Dystrophy Type 2(GCD II) is an autosomal dominant mutation associated with the transforming growth factor (TGF)-beta. It arises from a mutation in exon 4, codon 124 of the transforming growth factor, beta-induced (BIGH3) gene, where arginine is substituted by histidine.

Characteristics

Heterozygous patients of Granular Corneal Dystrophy Type 2 experience progressive corneal opacification over time, which can be categorized into three stages.
Initially, small, well-defined granular deposits form under the corneal epithelium and anterior stroma. Over time, these deposits increase in size and number, evolving into linear or star-shaped formations. In advanced stages, the opacification progresses to involve the mid and posterior stroma, leading to general stromal opacity.
Despite advancing age, heterozygous individuals may maintain good vision until the late stages, when overall corneal opacification between the granular deposits leads to vision impairment.

Prevalence

This form of corneal dystrophy is most commonly reported in Vietnam, Japan, and Korea, with an estimated prevalence of 1/870 in Korea.

Causative Gene

TGFBI R124H

Reis–Bücklers Corneal
Dystrophy (RBCD)

Also known as Granular Corneal Dystrophy Type 3, Reis-Bücklers Corneal Dystrophy predominantly affects the central part of the Bowman’s layer of the cornea. It is an autosomal dominant genetic disorder characterized by uniformly distributed, cloud-like, greyish deposits throughout the cornea.

Characteristics

The disease typically manifests around 4-5 years old, with irregular ring-shaped lesions, discontinuous spots, and lines extending as high as the corneal epithelial cells. It is known for causing rapid vision loss.
Before the onset of severe symptoms such as epithelial erosions, intense eye redness, pain, and light sensitivity, Reis-Bücklers Corneal Dystrophy often remains latent with no significant symptoms. Progressive epithelial opacification leads to vision loss, usually between the ages of 20 and 30.
Compared to other types of granular corneal dystrophy, Reis-Bücklers tend to appear earlier and are associated with a higher frequency of corneal erosions.
It is clinically similar to Thiel-Behnke Corneal Dystrophy but generally presents more severe symptoms.

Prevalence

The exact prevalence of Reis-Bücklers Corneal Dystrophy is currently unknown.

TGFBI R124L

Thiel–Behnke Corneal
Dystrophy (TBCD)

Thiel-Behnke Corneal Dystrophy is an autosomal dominant genetic disorder characterized by honeycomb-shaped deposits forming under the epithelial basal lamina and Bowman’s layer, leading to progressive visual impairment.

Characteristics

Corneal erosions begin to appear in the teenage or early twenties, often accompanied by discomfort and pain in the eye. These erosions are recurrent and progressively lead to continuous vision loss. Histologically, Thiel-Behnke Corneal Dystrophy is characterized by varying thicknesses of corneal epithelial cells. The epithelial basal lamina and Bowman's layer exhibit diverse degenerative changes, and atypical collagen tissue can be found in the subepithelial layer.
Thiel-Behnke Corneal Dystrophy has clinical similarities to Reis-Bücklers Corneal Dystrophy but is generally known to be less severe.

Prevalence

The exact prevalence of Thiel-Behnke Corneal Dystrophy is not known, although cases have been reported in Germany, the United States, and several other countries.

Causative Gene

TGFBI R555Q

Lattice Corneal Dystrophy,
type 1 (LCD1)

Lattice Corneal Dystrophy, Type 1, is an autosomal dominant genetic disease characterized by amyloid deposition in the corneal stroma, leading to vision impairment and sometimes recurrent corneal erosions.

Characteristics

The disease starts with linear opacifications in the central Bowman's layer, spreading to the periphery and stroma. The opacities intersect to form a lattice pattern and appear similar to the spread of nerves. Recurrent corneal erosions can precede the opacification, causing episodes of intense pain. It often begins to manifest in late adolescence, although onset can be delayed in some cases.
Lattice Corneal Dystrophy, Type 1, progresses very slowly but leads to vision impairment from an early stage, usually resulting in significant discomfort and vision problems before the age of 60. Corneal sensory loss may occur, but no systemic diseases are associated.

Prevalence

The exact prevalence of Lattice Corneal Dystrophy, Type 1, is not reported. Although it is generally more common in Western regions, the disease has been reported globally.

Causative Gene

TGFBI R124C

Why is Corneal Dystrophy Dangerous?

Once corneal dystrophy begins to develop, there is currently no way to treat it.
Therefore, delaying the onset and progression of the disease is the best course of action.

Prevalence of Corneal Dystrophy

South Korea

: 1 in 0 people

United States

: 1 in 0 people

China

: 1 in 0 people

(Based on Type 2 Granular Corneal Dystrophy – Avellino Corneal Dystrophy in South Korea)

Distribution of Corneal Dystrophy Gene Mutation by Region

Avellino Lab Universal Test

Testing Five Main Corneal Dystrophies

Avellino Lab Universal Test examines five main TGFBI corneal dystrophy gene mutations, which account for the majority of cases involving corneal dystrophy gene mutation.

Management of Corneal Dystrophy in Daily Life

For individuals with corneal dystrophy gene mutations,
exposure to specific environmental factors can accelerate the progression of the disease.
These environmental factors include:

1. UV exposure

2. Physical damage to the cornea

(e.g., LASIK, LASEK, SMILE LASIK surgery, etc.)

It is important for individuals with corneal dystrophy gene mutations to minimize UV
exposure in their daily lives and avoid refractive surgeries such as LASIK, LASEK, and
SMILE LASIK, which can directly damage the cornea.

What is Corneal Dystrophy?

Causes

Various genes, including TGFBI(Transforming Growth Factor Beta-Induced), are known to contribute to the development of corneal dystrophy.

Symptoms

Five Types of TGFBI Corneal Dystrophy

: According to the IC3D classification, these five types classified as TGFBI Corneal Dystrophy are conditions that arise from mutations in the TGFBI (Transforming Growth Factor-Beta Induced) gene, which commonly express the keratoepithelin protein.

Granular Corneal Dystrophy Type 1(GCD1)

Characteristics

Prevalence

Causative Gene

Granular Corneal Dystrophy Type 2(GCD2)

Characteristics

Prevalence

Causative Gene

Reis–Bücklers Corneal Dystrophy (RBCD)

Characteristics

Prevalence

TGFBI R124L

Thiel–Behnke Corneal Dystrophy (TBCD)

Characteristics

Prevalence

Causative Gene

Lattice Corneal Dystrophy, type 1 (LCD1)

Characteristics

Prevalence

Causative Gene

Why is Corneal Dystrophy Dangerous?

Once corneal dystrophy begins to develop, there is currently no way to treat it. Therefore, delaying the onset and progression of the disease is the best course of action.

Prevalence of Corneal Dystrophy

South Korea

United States

China

Distribution of Corneal Dystrophy Gene Mutation by Region

Avellino Lab Universal Test

Management of Corneal Dystrophy in Daily Life

For individuals with corneal dystrophy gene mutations, exposure to specific environmental factors can accelerate the progression of the disease. These environmental factors include:

1. UV exposure

2. Physical damage to the cornea

It is important for individuals with corneal dystrophy gene mutations to minimize UV exposure in their daily lives and avoid refractive surgeries such as LASIK, LASEK, and SMILE LASIK, which can directly damage the cornea.

Various genes, including TGFBI(Transforming Growth Factor Beta-Induced), are known to contribute to the
development of corneal dystrophy.

: According to the IC3D classification, these five types classified as TGFBI Corneal Dystrophy
are conditions that arise from mutations in the TGFBI (Transforming Growth Factor-Beta
Induced) gene, which commonly express the keratoepithelin protein.

Granular Corneal
Dystrophy Type 1(GCD1)

Granular Corneal
Dystrophy Type 2(GCD2)

Reis–Bücklers Corneal
Dystrophy (RBCD)

Thiel–Behnke Corneal
Dystrophy (TBCD)

Lattice Corneal Dystrophy,
type 1 (LCD1)

Once corneal dystrophy begins to develop, there is currently no way to treat it.
Therefore, delaying the onset and progression of the disease is the best course of action.

For individuals with corneal dystrophy gene mutations,
exposure to specific environmental factors can accelerate the progression of the disease.
These environmental factors include:

It is important for individuals with corneal dystrophy gene mutations to minimize UV
exposure in their daily lives and avoid refractive surgeries such as LASIK, LASEK, and
SMILE LASIK, which can directly damage the cornea.