Hereditary Retinal Dystrophies

Hereditary retinal dystrophies (HRD) encompass a group of diseases that affect the anatomy or function of the retina. Their main characteristic is the progressive loss of photoreceptors, leading to vision loss. In fact, they are the leading cause of hereditary blindness worldwide.

Depending on the affected area, two types of HRD are distinguished:

• Macular dystrophies: affect the central area of the retina (macula), responsible for sharp visual acuity.
• Peripheral dystrophies: begin with deterioration of the peripheral visual field, mainly affecting the rods, and progress to damage the central vision.

Among the most common hereditary retinal dystrophies are:

• Retinitis pigmentosa: a progressive degeneration of the retina due to the progressive degeneration of photoreceptors, initially and especially the rods.
• Leber's congenital amaurosis: a congenital or very early onset condition, where photoreceptors in the retina neurodegenerate and gradually deteriorate.
• Choroideremia: gradual degradation of the choroid (the middle layer of the eye), retina, and retinal pigment epithelium.
• Stargardt disease: accumulation of lipofuscin (a brown pigment) in the retinal epithelial tissue, mainly affecting central vision and leading to vision loss (visual acuity); also associated with photophobia.
• Viteliform macular dystrophy or Best disease: accumulation of fat in the macula.
• Retinoschisis: separation of the inner layers of the retina, leading to the formation of cysts or spaces between them.
• Wagner-Stickler disease: the central vitreous is empty and peripheral abnormalities occur.
• Familial exudative vitreoretinopathy: lack of blood vessel formation at the retinal borders, leading to poor circulation.

Hereditary retinal dystrophies are considered rare diseases, affecting approximately one in every 3,000 to 4,000 people. The prognosis varies depending on the type of pathology. Fortunately, treatments have been developed to slow the progression of most of them.

Symptoms

The symptoms of hereditary retinal dystrophy vary widely, although some are common across many types. The most frequent include:

• Blurred vision.
• Floaters: opaque spots or webs in vision.
• Metamorphopsia: straight lines appear wavy.
• Changes in the visual field: alterations in central or peripheral vision.
• Altered color perception.
• Night blindness or poor adaptation to darkness.
• Intolerance to intense light.

Other extraocular or syndromic DR symptoms:

In 15-20% of cases, in addition to ocular alterations, other symptoms may appear, such as hearing problems (Usher syndrome), obesity or polydactyly (Bardet-Biedl syndrome), renal issues (Senior-Loken syndrome), or neurological problems (Joubert syndrome and others).

Causes

Although environmental factors sometimes play a role, genetics is the primary cause of HRD, which are transmitted from one generation to the next in various ways:

• Dominant inheritance: carriers of the genetic mutation exhibit the disease, so it appears in all generations.
• Recessive inheritance: only individuals with two abnormal genes develop the condition, so it usually appears in a single generation.
• X-linked inheritance: only men suffer from the disease, although women can be carriers.

Some of the genes responsible for hereditary retinal dystrophies include ABCA4 (Stargardt disease), USH2A (Non-syndromic Retinitis Pigmentosa or Usher syndrome), RHO, PRPF31 (Retinitis Pigmentosa), RPE65, CRB1 (Early-onset Retinitis Pigmentosa or Leber’s Congenital Amaurosis), FZD4, LRP5, and NFP (familial exudative vitreoretinopathy), RS1 (retinoschisis), CSPG2 and VCAN (Wagner-Stickler disease), and BEST (viteliform macular dystrophy).

Risk Factors

The most significant risk factor is having a family history, as this is a hereditary disease. Other factors that influence the condition include aging, smoking, obesity, and diabetes.

Complications

Hereditary retinal dystrophies are associated with:

• Cataracts.
• Retinal detachment.
• Macular edema (fluid accumulation in the macula).
• Macular subretinal neovascularization (growth of blood vessels beneath the retina).
• Blindness.

Prevention

HRD cannot be prevented, as they are caused by genetic alterations.

What Doctor Treats Hereditary Retinal Dystrophy?

Ophthalmologists and geneticists are involved in diagnosing and treating HRD. In syndromic cases, other specialists may also be involved. Additionally, optometrists and low vision specialists can play a useful role.