X-linked retinitis pigmentosa: clinical manifestations and diagnosis

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Abstract

X-linked retinitis pigmentosa (XLRP) is considered one of the most severe forms of retinitis pigmentosa (RP). It accounts for 6–20% of all disease cases. Nowadays, mutations in three genes (RP2, RPGR, and OFD1) have been identified to cause XLRP. Early symptoms are impaired night vision and/or visual field loss. The subsequent damage to the cones results in decreased visual acuity, photophobia and color vision disorders may also be observed. Ophthalmoscopy shows waxy optic disc pallor, vasoconstriction, foci of hypopigmentation and/or hyperpigmentation, sometimes in form of bone-spicule in the peripheral retina. Gradual reduction in amplitudes of light-adapted and dark-adapted electroretinograms (ERG) is specific for RP. Microperimetry reveals reduced average light sensitivity and paracentral ring scotoma despite normal or slightly decreased visual acuity. Optical coherence tomography (OCT) demonstrates destructed outer retinal layers, short-wavelength autofluorescence imaging shows a Robson-Holder ring. X-linked RP in females is almost always associated with notable variability in severity from asymptomatic cases to severe ones as in male patients. Night blindness is reported in 50% of female carriers of X-linked RP, visual acuity and amplitude of light-adapted and dark-adapted ERG are reduced in most cases. Fundus changes are observed in 87% of female carriers. A tapetal reflex is the most common. Foci of hypo- and hyperpigmentation, bone-spicule-like pigment clumping, extensive retinal pigment epithelial and choroidal atrophy are also reported. In the vast majority (63–79%) of female carriers of X-linked RP, short-wavelength autofluorescence images show radial patterns.

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About the authors

Elena N. Demchenko

Helmholtz National Medical Research Center of Eye Diseases

Author for correspondence.
Email: ddddemchenko@yandex.ru
ORCID iD: 0000-0001-6523-5191

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

References

  1. Tsang SH, Sharma T. X-linked retinitis pigmentosa. Adv Exp Med Biol. 2018;1085:31–35. doi: 10.1007/978-3-319-95046-4_8
  2. Raghupathy RK, McCulloch DL, Akhtar S, et al. Zebrafish model for the genetic basis of X-linked retinitis pigmentosа. Zebrafish. 2013;10(1):62–69. doi: 10.1089/zeb.2012.0761
  3. Martinez-Fernandez De La Camara C, Nanda A, Salvetti AP, et al. Gene therapy for the treatment of X-linked retinitis pigmentosa. Exp Opin Orphan Drugs. 2018;6(3):167–177. doi: 10.1080/21678707.2018.1444476
  4. Fahim AT, Daiger SP, Weleber RG, et al. Nonsyndromic retinitis pigmentosa overview. Seattle (WA): University of Washington, Seattle; 1993.
  5. Lyraki R, Megaw R, Hurd T. Disease mechanisms of X-linked retinitis pigmentosa due to RP2 and RPGR mutations. Biochem Soc Trans. 2016;44(5):1235–1244. doi: 10.1042/BST20160148
  6. Hereditary and congenital diseases of the retina and optic nerve: a guide for doctors. Ed. by A.M. Shamshinova. Moscow: Meditsina; 2001. 528 р. (In Russ.)
  7. Padnick-Silver L, Kang Derwent JJ, Giuliano E, et al. Retinal oxygenation and oxygen metabolism in Abissinian with a hereditary retinal degeneration. Invest Ophtalmol Vis Sci. 2006;47(8):3683–3689. doi: 10.1167/iovs.05-1284
  8. Li L, Rao KN, Zheng-Le Y, et al. Loss of retinitis pigmentosa 2 (RP2) protein predominantly affects cone photoreceptor sensory cilium elongation in mice. Cytoskeleton (Hoboken). 2015;72(9):447–454. doi: 10.1002/cm.21255
  9. Li L, Khan N, Hurd T, et al. Ablation of the X-linked retinitis pigmentosa 2 (Rp2) gene in mice results in opsin mislocalization and photoreceptor degeneration. Invest Ophthalmol Vis Sci. 2013;54(7):4503–4511. doi: 10.1167/iovs.13-12140
  10. Georgiou M, Robson AG, Jovanovic K, et al. RP2-associated X-linked retinopathy: clinical findings, molecular genetics, and natural history. Ophthalmology. 2023;130(4):413–422. doi: 10.1016/j.ophtha.2022.11.015
  11. Tzu JH, Arguello T, Berrocal AM, et al. Clinical and electrophysiologic characteristics of a large kindred with x-linked retinitis pigmentosa associated with the RPGR locus. Ophthalmic Genet. 2015;36(4):321–326. doi: 10.3109/13816810.2014.886267
  12. Milash SV, Zolnikova IV, Kadyshev VV. Multimodal imaging of hereditary retinal dystrophies (a series of clinical cases). Russian Ophihalmological Journal. 2020;13(4):75–82. EDN: IMQTHJ doi: 10.21516/2072-0076-2020-13-4-75-82
  13. Kurata K, Hosono K, Hayashi T, et al. X-linked retinitis pigmentosa in Japan: clinical and genetic findings in male patients and female carriers. Int J Mol Sci. 2019;20(6):1518. doi: 10.3390/ijms20061518
  14. Sharon D, Sandberg MA, Rabe VW, et al. RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa. Am J Hum Genet. 2003;73(5):1131–1146. doi: 10.1086/379379
  15. Jayasundera T, Branham KE, Othman M, et al. RP2 phenotype and pathogenetic correlations in X-linked retinitis pigmentosa. Arch Ophthalmol. 2010;128(7):915–923. doi: 10.1001/archophthalmol.2010.122
  16. Talib M, van Schooneveld MJ, Thiadens AA, et al. Clinical and genetic characteristics of male patients with RPGR-associated retinal dystrophies: a long-term follow-up study. Retina. 2019;39(6):1186–1199. doi: 10.1097/IAE.0000000000002125
  17. Cehajic-Kapetanovic J, Xue K, Martinez-Fernandez de la Camara C, et al. Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nat Med. 2020;26(3):354–359. doi: 10.1038/s41591-020-0763-1
  18. Menghini M, Cehajic-Kapetanovic J, MacLaren RE. Monitoring progression of retinitis pigmentosa: current recommendations and recent advances. Expert Opin Orphan Drugs. 2020;8(2-3):67–78. doi: 10.1080/21678707.2020.1735352
  19. Buckley TM, Jolly JK, Josan AS, et al. Clinical applications of microperimetry in RPGR-related retinitis pigmentosa: a review. Acta Ophthalmol. 2021;99(8):819–825. doi: 10.1111/aos.14816
  20. Von Krusenstiern L, Liu J, Liao E, et al. Changes in retinal sensitivity associated with cotoretigene toliparvovec in X-linked retinitis pigmentosa with RPGR gene variations. JAMA Ophthalmol. 2023;141(3):275–283. doi: 10.1001/jamaophthalmol.2022.6254
  21. Hood DC, Lazow MA, Locke KG, et al. The transition zone between healthy and diseased retina in patients with retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2011;52(1):101–108. doi: 10.1167/iovs.10-5799
  22. Tee JL, Carroll J, Webster AR, Michaelides M. Quantitative analysis of retinal structure using spectral-domain optical coherence tomography in RPGR-associated retinopathy. Am J Ophthalmol. 2017;178:18–26. doi: 10.1016/j.ajo.2017.03.012
  23. Tang PH, Jauregui R, Tsang SH, et al. Optical coherence tomography angiography of RPGR-associated retinitis pigmentosa suggests foveal avascular zone is a biomarker for vision loss. Ophthalmic Surg Lasers Imaging Retina. 2019;50(2):e44–e48. doi: 10.3928/23258160-20190129-18
  24. Robson AG, El-Amir A, Bailey C, et al. Pattern ERG correlates of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Invest Ophthalmol Vis Sci. 2003;44(8):3544–3550. doi: 10.1167/iovs.02-1278
  25. Lima LH, Cella W, Greenstein VC, et al. Structural assessment of hyperautofluorescent ring in patients with retinitis pigmentosa. Retina. 2009;29(7):1025–1031. doi: 10.1097/iae.0b013e3181ac2418
  26. Oishi A, Ogino K, Makiyama Y, et al. Wide-field fundus autofluorescence imaging of retinitis pigmentosa. Ophthalmology. 2013;120(9):1827–1834. doi: 10.1016/j.ophtha.2013.01.050
  27. Lam BL, Davis JL, Gregori NZ. Choroideremia gene therapy. Int Ophthalmol Clin. 2021;61(4):185–193. doi: 10.1097/IIO.0000000000000385
  28. Fishman GA, Weinberg AB, McMahon TT. X-linked recessive retinitis pigmentosa. Clinical characteristics of carriers. Arch Ophthalmol. 1986;104(9):1329–1335. doi: 10.1001/archopht.1986.01050210083030
  29. Comander J, Weigel-DiFranco C, Sandberg MA, Berson EL. Visual function in carriers of X-linked retinitis pigmentosa. Ophthalmology. 2015;122(9):1899–1906. doi: 10.1016/j.ophtha.2015.05.039
  30. Acton JH, Greenberg JP, Greenstein VC, et al. Evaluation of multimodal imaging in carriers of X-linked retinitis pigmentosa. Exp Eye Res. 2013;113:41–48. doi: 10.1016/j.exer.2013.05.003
  31. Jacobson SG, Buraczynska M, Milam AH, et al. Disease expression in X-linked retinitis pigmentosa caused by a putative null mutation in the RPGR gene. Invest Ophthalmol Vis Sci. 1997;38(10):1983–1997.
  32. Vingolo EM, Livani ML, Domanico D, et al. Optical coherence tomography and electro-oculogram abnormalities in X-linked retinitis pigmentosa. Doc Ophthalmol. 2006;113(1):5–10. doi: 10.1007/s10633-006-9007-z
  33. Grover S, Fishman GA, Anderson RJ, Lindeman M. A longitudinal study of visual function in carriers of X-linked recessive retinitis pigmentosa. Ophthalmology. 2000;107(2):386–396. doi: 10.1016/s0161-6420(99)00045-7
  34. Wegscheider E, Preising MN, Lorenz B. Fundus autofluorescence in carriers of X-linked recessive retinitis pigmentosa associated with mutations in RPGR, and correlation with electrophysiological and psychophysical data. Graefes Arch Clin Exp Ophthalmol. 2004;242(6):501–511. doi: 10.1007/s00417-004-0891-1
  35. Ogino K, Oishi M, Oishi A, et al. Radial fundus autofluorescence in the periphery in patients with X-linked retinitis pigmentosa. Clin Ophthalmol. 2015;9:1467–1474. doi: 10.2147/OPTH.S89371

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Fundus (a) and optical coherence tomography (b) images of a patient with X-linked retinitis pigmentosa. ORF15 mutation, corrected visual acuity 0.3: a — Foci of hypo- and hyperpigmentation, b — Destructed outer retinal layers, ellipsoid zone is observed only in the foveal and parafoveal regions

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3. Fig. 2. Fundus tapetal reflex in a female carrier of X-linked retinitis pigmentosa (by S.V. Milash)

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4. Fig. 3. Fundus (a) and optical coherence tomography (b) images of the mother of the patient with X-linked retinitis pigmentosa; ORF15 mutation; visual acuity: hand motion

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5. Fig. 4. Radial pattern on short-wavelength autofluorescence images of a female carrier of X-linked retinitis pigmentosa (by S.V. Milash)

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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