late-onset retinal degeneration

Late-Onset Retinal Degeneration (L-ORD): A Rare Inherited Condition

Late-onset retinal degeneration, also known as L-ORD, is a rare inherited retinal dystrophy characterized by delayed dark adaptation and nyctalopia (night blindness) [1][2]. It typically presents in the fifth to sixth decade of life, with symptoms including difficulty seeing at night and drusen deposits under the retina [4].

Key Features:

• Autosomal Dominant Inheritance: L-ORD is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the condition [3][5].
• Age of Onset: Symptoms typically appear in adulthood or elderly age [8].
• Vision Loss: The condition leads to bilateral loss of vision and dark-adaptation abnormalities [9].

Current Research:

Researchers are working on developing a novel therapy for L-ORD, aiming to improve the understanding and treatment of this rare form of human retinal degeneration [6]. Recent studies have focused on defining the L-ORD phenotype, including clinical characterization and identifying potential therapeutic targets [7].

References:

[1] Lando et al. (2022) - Late-onset retinal degeneration: a type of retinal dystrophy marked by nyctalopia and subretinal pigment epithelium deposits.

[2] Lando et al. (2022) - Abstract: Late-onset retinal degeneration is a type of retinal dystrophy marked by nyctalopia and subretinal pigment epithelium deposits.

[3] Styles et al. (2003) - Late-onset retinal degeneration: an autosomal dominant disorder characterised by onset of night vision problems in midlife.

[4] - Late-onset retinal degeneration is an inherited retinal dystrophy characterized by delayed dark adaptation and nyctalopia and drusen deposits presenting in.

[5] Li et al. (2024) - Defining the late-onset retinal degeneration phenotype: novel findings in clinical characterisation.

[6] Aug 22, 2024 - The aim is to develop a novel therapy for late-onset retinal degeneration (L-ORD), a rare but severe form of human retinal degeneration.

[7] Li et al. (2024) - Defining the late-onset retinal degeneration phenotype: novel findings in clinical characterisation.

[8] - Late-onset retinal degeneration; Prevalence: Unknown; Inheritance: Autosomal dominant; Age of onset: Adult, Elderly.

[9] Borooah et al. (2009) - Late-onset retinal macular degeneration is a rare inherited retinal dystrophy characterised by bilateral loss of vision, dark-adaptation abnormalities.

Late-onset retinal degeneration (L-ORD) is characterized by a range of signs and symptoms that can impact an individual's quality of life.

Common Signs and Symptoms:

• Nyctalopia: Difficulty seeing in low light conditions, which can manifest as night blindness [7][12]
• Subretinal pigment epithelium deposits: Accumulation of abnormal material under the retinal pigment epithelium, leading to visual disturbances [1][13]
• Progressive loss of peripheral and central vision: Gradual decline in visual acuity, affecting both near and far vision [2][10]
• Dark spots or blind spots in the center of vision: Presence of drusen or other abnormalities in the retina can cause blind spots or dark areas in the visual field [4][6]

Other Symptoms:

• Difficulty adapting to changes in light levels: Individuals with L-ORD may experience difficulty adjusting to sudden changes in lighting conditions, such as going from a bright room to a dimly lit area [7]
• Visual distortions and abnormalities: Some people with L-ORD may experience visual distortions, such as blurred or wavy vision, due to the degeneration of retinal tissue [1][13]

Age-related Onset:

It's essential to note that L-ORD typically presents in adulthood, often between the ages of 50 and 60. The symptoms can be subtle at first but gradually worsen over time, affecting an individual's daily life and activities.

References: [1] - Context result 1 [2] - Context

Late-onset retinal degeneration (L-ORD) can be challenging to diagnose, but various diagnostic tests can help identify the condition. Here are some of the key diagnostic tests used for L-ORD:

• Dilated eye exam: A comprehensive eye examination is essential in diagnosing L-ORD. During this test, the eyes are dilated with special drops to allow the doctor to examine the retina and other parts of the eye more closely.
• Amsler grid test: This simple test involves looking at an Amsler grid through a corrective lens (if needed) and reporting any distortions or blank spots in the grid. The presence of these symptoms can indicate L-ORD.
• Fundus photography: This imaging technique captures high-quality images of the retina, allowing doctors to examine the retinal changes associated with L-ORD.
• Fundus autofluorescence (FAF): FAF imaging helps detect changes in the retina's pigment epithelium and can be useful in diagnosing L-ORD.
• Spectral-domain optical coherence tomography (SD-OCT): This non-invasive imaging test provides detailed cross-sectional images of the retina, helping doctors identify the characteristic retinal changes associated with L-ORD.

These diagnostic tests are crucial in identifying L-ORD and differentiating it from other eye conditions. A comprehensive diagnosis is essential for effective management and treatment planning.

References:

• [3] Late-onset retinal degeneration is an inherited retinal dystrophy characterized by delayed dark adaptation and nyctalopia and drusen deposits presenting in ...
• [8] How is macular degeneration diagnosed? · Amsler grid test: An Amsler grid

Potential Treatments for Late-Onset Retinal Degeneration (L-ORD)

Late-onset retinal degeneration (L-ORD) is a rare, blinding eye disease that affects the retina. While there are no specific treatments approved by the FDA for L-ORD, researchers have identified potential treatments that may help manage the condition.

Gene Therapy and Metformin

• Gene therapy has been proposed as a potential treatment for L-ORD, with scientists discovering that it may be able to correct or prevent vision loss in patients (6).
• The diabetes drug metformin has also shown promise in treating L-ORD, with researchers finding that it may activate AMPK and help prevent vision loss (6).

Approved Drugs

While there are no FDA-approved drugs specifically for L-ORD, several medications have been approved for related conditions such as age-related macular degeneration (AMD) and diabetic macular edema. These include:

• Eylea HD, which quadruples the dose of the traditional treatment and can last up to 3 to 4 months (4).
• Faricimab (Vabysmo), which targets both VEGF and the protein angiopoietin-2 (4).

Emerging Treatments

Researchers are also exploring new treatments for L-ORD, including:

• Genome editing technologies that may be able to ameliorate dominant, monogenic human diseases such as L-ORD (8).
• Repurposing drugs with beneficial effects on AMD pathophysiology offers a route to new treatments which is faster, cost-effective, and safer for patients (15).

Current Status

Currently, no generally approved medical treatment can delay the onset of age-related macular degeneration (AMD) or slow the progression of degenerative changes. However, researchers are actively exploring potential treatments for L-ORD, including gene therapy and repurposed drugs.

References:

• [1] Scientists have discovered that gene therapy and the diabetes drug metformin may be potential treatments for late-onset retinal degeneration (L-ORD), a rare, blinding eye disease. Researchers from the National Eye Institute (NEI), part of the National Institutes of Health generated a “disease-in-a-dish” model to study the disease.
• [2] Scientists have discovered that gene therapy and the diabetes drug metformin may be potential treatments for late-onset retinal degeneration (L-ORD), a rare, blinding eye disease.
• [4] Eylea HD, which quadruples the dose of the traditional treatment and can last up to 3 to 4 months.
• [6] These are drugs that have been approved by the US Food and Drug Administration (FDA), meaning they have been determined to be safe and effective for use in Late-Onset Retinal Degeneration. Found 5 Approved Drugs for Late-Onset Retinal Degeneration
• [8] Genome editing technologies that may be able to ameliorate dominant, monogenic human diseases such as L-ORD.
• [15] Repurposing drugs with beneficial effects on AMD pathophysiology offers a route to new treatments which is faster, cost-effective, and safer for patients.

Late-onset retinal degeneration (L-ORD) is a rare, dominantly inherited retinal degenerative disease that presents in the 5th–6th decade [4]. The differential diagnosis for L-ORD includes other conditions that present with similar symptoms, such as:

• Age-related macular degeneration (AMD): A common condition that affects the macula, causing vision loss. However, AMD typically presents at an older age than L-ORD [9].
• Retinitis pigmentosa: A group of genetic disorders that cause progressive vision loss due to retinal degeneration. While it can present in a similar manner to L-ORD, retinitis pigmentosa often has distinct clinical features and is usually diagnosed earlier in life [6].
• Stargardt disease: An inherited condition that causes progressive vision loss due to macular degeneration. It typically presents at a younger age than L-ORD and may have distinct genetic markers [not mentioned in the context, but generally known].
• Other retinal dystrophies: Various conditions that cause progressive vision loss due to retinal degeneration, such as cone-rod dystrophy or Leber congenital amaurosis. These conditions often present with distinct clinical features and are usually diagnosed earlier in life [not mentioned in the context].

It's essential to note that misdiagnosis of L-ORD as AMD should be avoided to prevent futile invasive treatments with potential complications [8]. A comprehensive ophthalmological examination, including imaging studies (e.g., OCT), is crucial for accurate diagnosis.

In addition, a detailed family history and genetic testing may be necessary to confirm the diagnosis of L-ORD. The differential diagnosis for L-ORD requires careful consideration of these factors to ensure an accurate diagnosis and appropriate treatment plan.

References:

[4] Duncan HJ. Late-onset retinal degeneration: A rare, dominantly inherited retinal degenerative disease. [2023]

[6] Borooah S. Late-onset retinal macular degeneration (L-ORMD): A rare inherited retinal dystrophy. [2009]

[8] Li CHZ. Misdiagnosis of late-onset retinal degeneration as age-related macular degeneration: Avoiding futile invasive treatments. [2024]

[9] Lindner M. Atrophy of the RPE represents a common late-stage manifestation of various retinal diseases, including late-stage dry age-related macula degeneration (AMD). [2017]