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Congenital blindness

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Human eye anatomy

Congenital blindness refers to blindness present at birth.[1] Congenital blindness is sometimes used interchangeably with "Childhood Blindness." However, current literature has various definitions of both terms. Childhood blindness encompasses multiple diseases and conditions present in ages up to 16 years old, which can result in permanent blindness or severe visual impairment over time.[2] Congenital blindness is a hereditary disease and can be treated by gene therapy. Visual loss in children or infants can occur either at the prenatal stage (during the time of conception or intrauterine period) or postnatal stage (immediately after birth).[3] There are multiple possible causes of congenital blindness. In general, 60% of congenital blindness cases are contributed from prenatal stage and 40% are contributed from inherited disease.[4] However, most of the congenital blindness cases show that it can be avoidable or preventable with early treatment.[5]

Signs and symptoms

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Coloboma in the right eye of a 10-month-old child

There are two categories in which the signs of congenital blindness can be classified. The first category pertains to consistently poor vision, such as not displaying preferential looking when presented with high-contrast visual stimuli.[6] The second category encompasses severe ocular anomalies,[6] such as Anophthalmos (born with only one eye or lost both eyes), Microphthalmos (underdevelopment of one or both eyes), and Coloboma (a portion of tissue missing in the eye(s)).[7]

Causes

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Prenatal

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Retinopathy of prematurity

Mutations

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Gene alterations leading to retinal dystrophies or congenital malformations may cause congenital and childhood blindness.[7] Examples of these include:

  • Microphthalmia[7]
  • Anophthalmia[7]
  • Coloboma[7]
  • Leber's congenital amaurosis (LCA) is a collection of inherited, degenerative eye disorders that can reduce the strength of visual clarity or sharpness in infants and can cause childhood blindness.[14][15] These eye disorders are mostly autosomal recessive diseases, and diagnoses of LCA are linked to multiple gene variants, including the Retinal pigment epithelium-specific 65 kDa (RPE65) gene.[14][16] The RPE65 protein is essential in the process of vision, as it contributes to the regeneration process of the visual pigment rhodopsin.[17] During the normal visual cycle, all-trans-retinyl palmitate, a stored form of vitamin A, binds and activates retinoid isomerohydrolase.[17] This enzyme converts all-trans-retinyl palmitate into 11-cis-retinol, which is further oxidized into 11-cis-retinal.[17] This compound binds with apo-rhodopsin to become rhodopsin, concluding the visual cycle.[17] Biochemical studies suggest that the RPE65 protein binds with all-trans-retinyl palmitate and helps bring it to isomerohydrolase.[17][16] RPE65-associated LCA is characterized by dysfunctional isomerization activity and early-onset blindness.[17][16]
RPE65
  • Retinoblastoma is the most common intraocular malignancy present in children younger than 5 years old. The eye cancer can be passed down genetically as an autosomal dominant condition.[18][19]

Postnatal

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Screening

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As per the CDC recommendations, newborns should undergo an eye examination while they are still in the hospital nursery. It is equally important for caregivers to continue monitoring their eyes and vision system throughout their childhood and adolescence.[21]

Screening test: Snellen Chart

The following methods are used to test infant's vision:

Type of visual impairment Screening tests
Visual acuity (Being able to tell and recognize the sharp and well-defined visual information when there is a noticeable contrast between light and dark areas)[22]
  • HOTV eye test
  • Picture identification tests
  • Tumbling E
  • Snellen
Strabismus (Squint;[23] eyes are not looking in the same direction)
  • Hirschberg test (corneal light reflex test)
  • Cover-uncover test (cross cover test)
  • Bruckner test (red reflex test)
Anisometropia (Two eyes have varying refractive power)[24]
  • Stereo Smile
  • Random Dot E
  • TNO
Refractive errors
  • Photorefraction
  • Autorefractive screening

Diagnosis

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Pediatric nurses, medical officers and pediatricians trained in eye screening could detect small or large eyeballs, nystagmus, strabismus, “white pupils” and birth defects like coloboma and aniridia.[2] People that are pregnant from families with a history of congenital blindness will be closely monitored and need to carry out genetic testing in order to identify whether there is a mutation or not.

Red reflex testing is done in neonates, infants, and children to assess eye and vision function.[26] Red reflex testing is a low-cost preventative examination that should be completed at birth before discharge.[26] According to the American Academy of Ophthalmology, neonates found with eye abnormalities should be seen by a pediatric ophthalmologist immediately.[27]

Epidemiology

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Of all the children in the world, about 19 million of them are estimated to be visually impaired or blind.[28] There is evidence that the prevalence of visual impairment or blindness in children is much higher as many studies use data that are at risk bias and miss many children who fall under multiple categories of disadvantage (i.e. female, rural areas).[6] Many of the cases occurring in low-income countries in the previous two decades were a result of low socioeconomic status and its association with disease and nutritional deficiencies, such as vitamin A deficiency.[29] However, recent studies have shown that most cases of visually impaired children are a result of causes such as cerebral visual impairment and optic nerve anomalies.[29] This is due to a decrease in preventable or avoidable causes of blindness with the improvement and focus on maternal and neonatal healthcare worldwide.[6]

There is limited knowledge on how childhood blindness affects long-term quality of life as there have not been many studies done to assess overall outcomes.[30] However, there is data that supports the functional burden of blindness for both individuals that later affect society, such as education and employment.[6] Some potential questionnaires for gathering and assessing quality of life have been tested but not developed nor fully implemented in the healthcare system.[31][32] Treatments currently available for those who are diagnosed are not readily accessible in developing countries due to financial and institutional limitations.[33]

Research

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Leber congenital amaurosis (LCA) has been a major focus in the development of gene therapy for treatment of the disease, as it is the most severe form of congenital blindness and accounts for 5% of all inherited retinal diseases cases.[34][35] Research on gene therapy is aimed at slowing retinal degeneration and improving visual function.[36] Genetic testing is used to supplement clinical diagnosis and identify eligibility for future gene therapy use.[35] LCA diagnosis occurs at birth or within the first few months of birth, with all cases following similar signs, but some genotypes present with a more severe form of the disease.[36] There has since been a push for further research to investigate the role of gene therapy in the treatment of inherited retinal dystrophy.[37] In 2017, the U.S. Food and Drug Administration approved Voretigene neparvovec (Luxturna), a gene therapy medication used for the treatment of retinal dystrophy.[35]

Gene therapy treatment is done in the outpatient setting. Patients come to the hospital for the treatment, then return home. Patients do not need to be strictly monitored or stay in the hospital. The gene therapy treatment is in vivo which involves the use of a delivery vector to transmit the therapeutic gene into the targeted cells. People with congenital amaurosis will present with reduced or absent levels of retinal pigment epithelium 65 kDa protein (RPE65).[38] Luxturna works by delivering a normal copy of the RPE65 gene.[38] The delivery vector uses a recombinant adeno-associated virus (AAV) carrying the RPE65 gene (AAV2-hRPE65v2).[39] The procedure is a single injection of the AAV2-hRPE65v2 therapeutic gene into the unilateral subretinal of the eye.[39] People must meet the following requirements to be eligible for Luxturna gene therapy: biallelic disease-causing RPE65 mutation, older than one year in age, no surgical contraindications, detectable photoreceptors and RPE, and measurable vision.[38] Luxturna has now become the standard of care for the treatment of inherited retinal dystrophy.[38] Due to the nature and rareness of inherited retinal disease, Luxturna was granted orphan drug designation by the FDA, which incentivizes pharmaceutical companies to continue innovating because tax credits are granted for qualified clinical trials.[40]

References

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  1. ^ "Congenital blindness (Concept Id: C0005754) - MedGen - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-07-27.
  2. ^ a b c Khandekar R (July 2008). "Visual disabilities in children including childhood blindness". Middle East African Journal of Ophthalmology. 15 (3): 129–134. doi:10.4103/0974-9233.51988. PMC 3040917. PMID 21369469.
  3. ^ "WHO Technical Consultation on Postpartum Care", WHO Technical Consultation on Postpartum and Postnatal Care, World Health Organization, 2010, retrieved 2023-08-01
  4. ^ "Genetic Eye Disorders & Blindness Causes | Cleveland Clinic: Health Library". Cleveland Clinic. Retrieved 2019-04-14.
  5. ^ "Blindness (Vision Impairment): Types, Causes and Treatment". Cleveland Clinic. Retrieved 2023-08-01.
  6. ^ a b c d e Solebo AL, Teoh L, Rahi J (August 2017). "Epidemiology of blindness in children". Archives of Disease in Childhood. 102 (9): 853–857. doi:10.1136/archdischild-2016-310532. PMID 28465303. S2CID 22904590.
  7. ^ a b c d e Basinski BW, Balikov DA, Aksu M, Li Q, Rao RC (February 2021). "Ubiquitous Chromatin Modifiers in Congenital Retinal Diseases: Implications for Disease Modeling and Regenerative Medicine". Trends in Molecular Medicine. 27 (4): 365–378. doi:10.1016/j.molmed.2021.01.001. PMC 8034778. PMID 33573910.
  8. ^ a b Gilbert C, Muhit M (September 2008). "Twenty years of childhood blindness: what have we learnt?". Community Eye Health. 21 (67): 46–47. PMC 2580065. PMID 19030129.
  9. ^ Taylan Şekeroğlu H, Utine GE (April 2021). "Congenital Cataract and Its Genetics: The Era of Next-Generation Sequencing". Turkish Journal of Ophthalmology. 51 (2): 107–113. doi:10.4274/tjo.galenos.2020.08377. PMC 8109038. PMID 33951899.
  10. ^ Kim SJ, Port AD, Swan R, Campbell JP, Chan RV, Chiang MF (September 2018). "Retinopathy of prematurity: a review of risk factors and their clinical significance". Survey of Ophthalmology. 63 (5): 618–637. doi:10.1016/j.survophthal.2018.04.002. PMC 6089661. PMID 29679617.
  11. ^ Lim HW, Pershing S, Moshfeghi DM, Heo H, Haque ME, Lambert SR (April 2023). "Causes of Childhood Blindness in the United States using the IRIS® Registry (Intelligent Research in Sight)". Ophthalmology. 130 (9): 907–913. doi:10.1016/j.ophtha.2023.04.004. PMC 10524509. PMID 37037315.
  12. ^ Tomita T, Guevara RB, Shah LM, Afrifa AY, Weiss LM (September 2021). "Secreted Effectors Modulating Immune Responses to Toxoplasma gondii". Life. 11 (9): 988. Bibcode:2021Life...11..988T. doi:10.3390/life11090988. PMC 8467511. PMID 34575137.
  13. ^ Fowler KB, Boppana SB (April 2018). "Congenital cytomegalovirus infection". Seminars in Perinatology. 42 (3): 149–154. doi:10.1053/j.semperi.2018.02.002. PMID 29503048.
  14. ^ a b Wang X, Yu C, Tzekov RT, Zhu Y, Li W (February 2020). "The effect of human gene therapy for RPE65-associated Leber's congenital amaurosis on visual function: a systematic review and meta-analysis". Orphanet Journal of Rare Diseases. 15 (1): 49. doi:10.1186/s13023-020-1304-1. PMC 7023818. PMID 32059734.
  15. ^ Allikmets R (June 2004). "Leber congenital amaurosis: a genetic paradigm". Ophthalmic Genetics. 25 (2): 67–79. doi:10.1080/13816810490514261. PMID 15370538. S2CID 40629207.
  16. ^ a b c Redmond TM, Poliakov E, Yu S, Tsai JY, Lu Z, Gentleman S (September 2005). "Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycle". Proceedings of the National Academy of Sciences of the United States of America. 102 (38): 13658–13663. Bibcode:2005PNAS..10213658R. doi:10.1073/pnas.0504167102. PMC 1224626. PMID 16150724.
  17. ^ a b c d e f Wolf G (March 2005). "Function of the protein RPE65 in the visual cycle". Nutrition Reviews. 63 (3): 97–100. doi:10.1111/j.1753-4887.2005.tb00127.x. PMID 15825812.
  18. ^ Wong ES, Choy RW, Zhang Y, Chu WK, Chen LJ, Pang CP, Yam JC (March 2022). "Global retinoblastoma survival and globe preservation: a systematic review and meta-analysis of associations with socioeconomic and health-care factors". The Lancet. Global Health. 10 (3): e380–e389. doi:10.1016/s2214-109x(21)00555-6. PMID 35093202.
  19. ^ "Retinoblastoma". National Eye Institute. U.S. Department of Health and Human Services. 2022. Retrieved 2023-07-30.
  20. ^ Kapoor VS, Evans JR, Vedula SS, et al. (Cochrane Eyes and Vision Group) (September 2020). "Interventions for preventing ophthalmia neonatorum". The Cochrane Database of Systematic Reviews. 2020 (9): CD001862. doi:10.1002/14651858.CD001862.pub4. PMC 8524318. PMID 32959365.
  21. ^ Jullien S (September 2021). "Vision screening in newborns and early childhood". BMC Pediatrics. 21 (Suppl 1): 306. doi:10.1186/s12887-021-02606-2. PMC 8424784. PMID 34496780.
  22. ^ Hamilton R, Bach M, Heinrich SP, Hoffmann MB, Odom JV, McCulloch DL, Thompson DA (February 2021). "VEP estimation of visual acuity: a systematic review". Documenta Ophthalmologica. Advances in Ophthalmology. 142 (1): 25–74. doi:10.1007/s10633-020-09770-3. PMC 7907051. PMID 32488810.
  23. ^ Gunton KB, Wasserman BN, DeBenedictis C (September 2015). "Strabismus". Primary Care. 42 (3): 393–407. doi:10.1016/j.pop.2015.05.006. PMID 26319345.
  24. ^ Barrett BT, Bradley A, Candy TR (September 2013). "The relationship between anisometropia and amblyopia". Progress in Retinal and Eye Research. 36: 120–158. doi:10.1016/j.preteyeres.2013.05.001. PMC 3773531. PMID 23773832.
  25. ^ Schiefer U, Kraus C, Baumbach P, Ungewiß J, Michels R (October 2016). "Refractive errors". Deutsches Ärzteblatt International. 113 (41): 693–702. doi:10.3238/arztebl.2016.0693. PMC 5143802. PMID 27839543.
  26. ^ a b Taksande A, Jameel PZ, Taksande B, Meshram R (August 2021). "Red reflex test screening for neonates: A systematic review and meta analysis". Indian Journal of Ophthalmology. 69 (8): 1994–2003. doi:10.4103/ijo.IJO_3632_20. PMC 8482932. PMID 34304165.
  27. ^ Donahue SP, Nixon CN, et al. (Section on Ophthalmology, American Academy of Pediatrics; Committee on Practice and Ambulatory Medicine, American Academy of Pediatrics; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus; American Association of Certified Orthoptists) (January 2016). "Visual System Assessment in Infants, Children, and Young Adults by Pediatricians". Pediatrics. 137 (1): 28–30. doi:10.1542/peds.2015-3596. PMID 29756730.
  28. ^ Jauregui R, Cho GY, Takahashi VK, Takiuti JT, Bassuk AG, Mahajan VB, Tsang SH (May 2018). "Caring for Hereditary Childhood Retinal Blindness". Asia-Pacific Journal of Ophthalmology. 7 (3): 183–191. doi:10.22608/APO.201851. PMID 29536675.
  29. ^ a b Ozturk T, Er D, Yaman A, Berk AT (February 2016). "Changing trends over the last decade in the aetiology of childhood blindness: a study from a tertiary referral centre". The British Journal of Ophthalmology. 100 (2): 166–171. doi:10.1136/bjophthalmol-2015-306737. PMID 26159454.
  30. ^ Rahi JS (October 2007). "Childhood blindness: a UK epidemiological perspective". Eye. 21 (10): 1249–1253. doi:10.1038/sj.eye.6702837. PMID 17914426.
  31. ^ Tadić V, Cooper A, Cumberland P, Lewando-Hundt G, Rahi JS (December 2013). "Development of the functional vision questionnaire for children and young people with visual impairment: the FVQ_CYP". Ophthalmology. 120 (12): 2725–2732. doi:10.1016/j.ophtha.2013.07.055. PMID 24120327.
  32. ^ Rahi JS, Tadić V, Keeley S, Lewando-Hundt G (May 2011). "Capturing children and young people's perspectives to identify the content for a novel vision-related quality of life instrument". Ophthalmology. 118 (5): 819–824. doi:10.1016/j.ophtha.2010.08.034. PMID 21126769.
  33. ^ Vinluan ML, Olveda RM, Olveda DU, Chy D, Ross AG (April 2015). "Access to essential paediatric eye surgery in the developing world: a case of congenital cataracts left untreated". BMJ Case Reports. 2015: bcr2014208197. doi:10.1136/bcr-2014-208197. PMC 4420824. PMID 25903202.
  34. ^ Koenekoop RK (2004). "An overview of Leber congenital amaurosis: a model to understand human retinal development". Survey of Ophthalmology. 49 (4): 379–398. doi:10.1016/j.survophthal.2004.04.003. PMID 15231395.
  35. ^ a b c Kondkar AA, Abu-Amero KK (December 2019). "Leber congenital amaurosis: Current genetic basis, scope for genetic testing and personalized medicine". Experimental Eye Research. 189: 107834. doi:10.1016/j.exer.2019.107834. PMID 31639339.
  36. ^ a b Kumaran N, Moore AT, Weleber RG, Michaelides M (September 2017). "Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions". The British Journal of Ophthalmology. 101 (9): 1147–1154. doi:10.1136/bjophthalmol-2016-309975. PMC 5574398. PMID 28689169.
  37. ^ Tuohy GP, Megaw R (May 2021). "A Systematic Review and Meta-Analyses of Interventional Clinical Trial Studies for Gene Therapies for the Inherited Retinal Degenerations (IRDs)". Biomolecules. 11 (5): 760. doi:10.3390/biom11050760. PMC 8160708. PMID 34069580.
  38. ^ a b c d Maguire AM, Bennett J, Aleman EM, Leroy BP, Aleman TS (February 2021). "Clinical Perspective: Treating RPE65-Associated Retinal Dystrophy". Molecular Therapy. 29 (2): 442–463. doi:10.1016/j.ymthe.2020.11.029. PMC 7854308. PMID 33278565.
  39. ^ a b Bennett J, Ashtari M, Wellman J, Marshall KA, Cyckowski LL, Chung DC, et al. (February 2012). "AAV2 gene therapy readministration in three adults with congenital blindness". Science Translational Medicine. 4 (120): 120ra15. doi:10.1126/scitranslmed.3002865. PMC 4169122. PMID 22323828.
  40. ^ Papaioannou I, Owen JS, Yáñez-Muñoz RJ (August 2023). "Clinical applications of gene therapy for rare diseases: A review". International Journal of Experimental Pathology. 104 (4): 154–176. doi:10.1111/iep.12478. PMC 10349259. PMID 37177842.
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