Retinal dystrophy

In this article:

• Treatment
• Gene therapy
• Stem cell therapy
• Retinal prostheses
• Brain-Machine Interfaces to Assist the Blind
• Light avoidance
• Antioxidants
• No smoking
• Lifestyle and home remedies
• References

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Treatment

Currently, retinal dystrophies cannot be cured. However, supportive treatment can improve the quality of life. Major advances are gene therapy and stem cell therapy. The options to improve quality of life is vision aids and refraction/cataract surgery when indicated. Patients with cystoid macular edema benefit from topical or systemic carbonic anhydrase inhibitors.

Patients with night vision problems benefit from night vision aid counselling to prevent falls. People with cone dystrophies with photosensitivity benefit from tinted orange or red lenses, since rod photoreceptors are less sensitive to orange and red lights. Red tinted soft contact lenses can be worn as an alternative to glasses. Genetic testing and counselling is important for the families with affected children.

A team approach to treatment of the children with retinal dystrophy should involve multiple specialists to help the family, such as:

• Pediatrician
• Geneticist
• Developmental specialist
• Pediatric ophthalmologist
• Retina specialist

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Gene therapy

Retina is a good target for gene therapy due to its nature:

• target cells (photoreceptors) are easily accessible for surgery and monitoring,
• the blood-retinal barrier provides an ocular immune privilege,
• the visual cells are static (do not divide), which requires a small amount of therapeutics to be administered.

Subretinal injection deliver gene therapy agents. Compared to intravitreal injections, the immunological response is well controlled. Several clinical trials are ongoing. In 2017, the US FDA approved subretinal injection of voretigene neparvovec for RPE65 associated Leber congenital amaurosis.

One randomized, open-label, phase III trial (Study 301, N = 31) evaluated the efficacy and safety of sequential subretinal injections of voretigene neparvovec to each eye in patients diagnosed with leber congenital amaurosis (LCA) due to RPE65 mutations.

Voretigene neparvovec demonstrated a statistically significant improvement in functional vision under low light conditions as measured by multi-luminance mobility testing (MLMT) at one year post-treatment compared with best supportive care (change from baseline in bilateral MLMT between-groups difference. This improvement in functional vision would likely be considered meaningful to patients. Voretigene neparvovec also resulted in a statistically significant improvement in full-field sensitivity threshold (FST) one year post-treatment.

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Stem cell therapy

Human pluripotent stem cells were first cultured in 1998 and were seen to have the potential to differentiate into endodermal, mesodermal, and ectodermal lineages. For reasons similar to gene therapy, the retina is a good target for stem cell therapy.

Moreover, the limited size of the retina requires smaller quantities of therapeutic tissue compared to other organs. Several trials are ongoing which mostly focus on diseases like age-related macular degeneration, Stargardt disease, glaucoma, and retinitis pigmentosa.

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Retinal prostheses

These are devices that replace phototransduction within the eyes of individuals lacking photoreceptors in diseases such as retinitis pigmentosa. Normally photoreceptors contain light-sensitive pigments that trigger phototransduction, which generate neuronal signals in presence of light stimuli.

These signals are processed by the middle layers of the retina before they reach ganglion cells. These retinal ganglion cells, that form the optic nerve, then transmit these signals to the visual cortex. In cases where the outer retinal layer/ photoreceptors are lost, retinal prosthesis transmits the signals to inner layers for the phototransduction pathway to be completed.

In 2013, USFDA approved Argus II retinal prosthesis for late-stage retinitis pigmentosa. Currently, many other retinal prostheses are under trial worldwide with an aim at exploring use in conditions like severe age-related macular degeneration, cone-rod dystrophy, choroideremia.

Argus II is composed of 60 electrodes that are implanted. External components include a video camera mounted on a pair of glasses, a visual processing unit, and a coil attached to the sidearm of glasses. Internal components are an internal coil, internal processing unit which is within a casing which is sutured to the sclera.

Currently, it is indicated in cases of retinitis pigmentosa who are > 25 years of age, with light perception or worse vision and a previous history of useful form vision. Patients must also be highly motivated for post-op clinic follow up and rehabilitation. Complications reported include retinal detachment, choroidal effusion, hypotony, endophthalmitis, and implant dislocation.

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Brain-Machine Interfaces to Assist the Blind

The loss or absence of vision is probably one of the most incapacitating events that can befall a human being. The importance of vision for humans is also reflected in brain anatomy as approximately one third of the human brain is devoted to vision. It is therefore unsurprising that throughout history many attempts have been undertaken to develop devices aiming at substituting for a missing visual capacity. In this review, we present two concepts that have been prevalent over the last two decades.

The first concept is sensory substitution, which refers to the use of another sensory modality to perform a task that is normally primarily sub-served by the lost sense. The second concept is cross-modal plasticity, which occurs when loss of input in one sensory modality leads to reorganization in brain representation of other sensory modalities. Both phenomena are training-dependent.

With the advent of brain imaging, it has become possible to peer into the neural substrates of sensory substitution and highlight the magnitude of the plastic processes that lead to a rewired brain. Finally, we will address the important question of the value and practicality of the available technologies and future directions.

Light avoidance

Direct light can be damaging to the retina cells. Cone photoreceptors are the sensors of bright light and different wavelengths of light in the retina. They are sensitive in photopic (bright light) conditions and come in several types according to the structure of the visual pigments or opsins in their outer segment regions.

Antioxidants

As with any genetic defects, there is no cure with natural treatments, but it is important to supply the body with the best building blocks such as essential amino acids, fatty acids, minerals and vitamins.

The most widely recommended treatment for many years has been supplementation with vitamin A, which some studies have shown to slow the rate of retinal deterioration. However, a recent Cochrane review found no significant benefit to vitamin A for RP. When individual patients are supplemented with high dose vitamin A, liver function tests should be monitored.

The brain and eye are highly enriched with omega-3 fatty acids, which accumulate in these tissues during late fetal and early neonatal life. Some studies in preterm and term human infants have suggested that a dietary supply of omega-3 fatty acids is essential for optimal visual development. Several basic science studies support the hypothesis that omega-3 fatty acids may be useful therapeutic agents for pathologies of the retina and lens.

No smoking

Smoking affects an ability of cells to regenerates and reduces cell oxygenation. It is important to have the healthy lifestyle to prevent fast progression of the eye disease.

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Lifestyle and home remedies

The cure for retinal dystrophy does not exist right now. But there is a big hope for genetic therapies in the future.

Blindness has a profound effect on the lifestyle and functioning of a child and adult affected.

As new therapies continue to be discovered, there is an ever-increasing need for the clinicians to recognize the clinical characteristics to determine whether the patients may benefit from a certain treatment.

All patients must be offered a referral to support services. This is particularly important when dealing with issues like vocational rehabilitation training and schooling of a visually impaired child.

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References

Brain-Machine Interfaces to Assist the Blind. Ptito M, Bleau M, Djerourou I, Paré S, Schneider FC, Chebat DR.Front Hum Neurosci. 2021 Feb 9;15:638887. doi: 10.3389/fnhum.2021.638887. eCollection 2021.PMID: 33633557 Free PMC article. Review.

Neural correlates of virtual route recognition in congenital blindness. Kupers R, Chebat DR, Madsen KH, Paulson OB, Ptito M.Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12716-21. doi: 10.1073/pnas.1006199107. Epub 2010 Jun 28.PMID: 20616025 Free PMC article.

Clinical Review Report: Voretigene Neparvovec (Luxturna): (Novartis Pharmaceuticals Canada Inc.): Indication: Vision loss, inherited retinaldystrophy. [No authors listed]Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2021 Jan.PMID: 33780202 Free Books & Documents. Review.

Effects of omega-3 fatty acids on eye health. Hodge W, Barnes D, Schachter HM, Pan Y, Lowcock EC, Zhang L, Sampson M, Morrison A, Tran K, Miguelez M, Lewin G.Evid Rep Technol Assess (Summ). 2005 Jul;(117):1-6.PMID: 16111433 Free PMC article. Review. 

Achromatopsia. Kohl S, Jägle H, Wissinger B, Zobor D.2004 Jun 24 [updated 2018 Sep 20]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2020.PMID: 20301591 Free Books & Documents. Review.

Choroideremia. MacDonald IM, Hume S, Zhai Y, Xu M.2003 Feb 21 [updated 2021 Mar 4]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021.PMID: 20301511 Free Books & Documents. Review.

Introduction to Visual Prostheses. Fernandez E, Normann R.2016 Mar 9. In: Kolb H, Fernandez E, Nelson R, editors. Webvision: The Organization of the Retina and Visual System [Internet]. Salt Lake City (UT): University of Utah Health Sciences Center; 1995–.PMID: 27809426 Free Books & Documents. Review.