Multimodal Imaging and Electrophysiological Features of Genetically Confirmed Inherited Retinal Dystrophies

Year 2026, Volume: 15 Issue: 1 , 155 - 164 , 28.02.2026

Gozde Sahın Vural , Hamıde Betul Gerik Celebi , Hilmi Bolat

https://doi.org/10.53424/balikesirsbd.1757960

https://izlik.org/JA23BW96BZ

Abstract

Objective: This study aimed to evaluate the relationship between ophthalmic features and genetic causes of inherited retinal disorders (IRDs). Materials and Methods: The patients who were diagnosed as IRDs were included, and divided into two groups: central and peripheral retinal dystrophy. The optic coherence tomography-angiography (OCT-A), and optic nerve head angiography were completed. The patients were referred to the Department of Genetics for a targeted exome sequencing. Results: The study included 56 eyes of 28 patients with IRDs with a mean age of 34.17±17.88 years. There was central retinal dystrophy in 50% of cases; while, peripheral retinal dystrophy was in 50% of cases. The most frequently detected gene mutation was ABCA4 (28.5%), followed by CRB1 (10.7%) and MFSD8, RPE65, and USH2A (each 7.1%). Other mutations included BEST1, LYST, MERTK, PDE, PROM1, RDH12, RHO (OPN2), RP9, and SPATA7 (each 3.5%). Electrophysiology supported functional characterization; however, ERG responses were frequently nonrecordable in advanced peripheral dystrophy, limiting quantitative comparisons between groups. In OCT-A, the macular superficial vessel density was significant (central 18.0±10.7µ, peripheral 43.0±10.3µ; p=0.003); while, there was no difference in optic nerve head angiography (p>0.05 in all quadrants). Conclusion: Although the patients with IRDs occur in the similar phenotype, they may have dissimilar genetic properties and ophtalmic findings.

Keywords

Electroretinography , Genetic Counceling , Retinal Dystrophies

Ethical Statement

Institution: Balikesir University Ethics Committee Date: 08.12.2021 Approval no: 2021/268.

Supporting Institution

The authors have no funding to declare.

Thanks

The authors would like to extend their sincere thanks to anyone who contributed to this study.

Genetik Olarak Doğrulanmış Kalıtsal Retina Distrofilerinin Multimodal Görüntüleme ve Elektrofizyolojik Özellikleri

https://izlik.org/JA23BW96BZ

Abstract

Amaç: Bu çalışma, kalıtsal retina distrofi (KRD) tanısı olan hastalarda oftalmik özellikler ile genetik etiyoloji arasındaki ilişkiyi değerlendirmeyi amaçlamaktadır. Gereç ve Yöntem: KRD tanısı alan hastalar çalışmaya dahil edildi ve iki gruba ayrıldı: santral retina distrofileri ve periferik retina distrofileri. Tüm hastalara optik koherens tomografi anjiyografi (OCT-A) ve optik sinir başı anjiyografisi uygulandı. Genetik nedenlerin belirlenmesi amacıyla Tıbbi Genetik Anabilim Dalı tarafından hedefe yönelik ekzom dizileme yapıldı. Bulgular: Toplamda 28 hastaya ait 56 göz (ortalama yaş: 34.17±17.88 yıl) çalışmaya dahil edildi. Hastaların %50’sinde santral, %50’sinde periferik retina distrofisi saptandı. En sık tespit edilen gen mutasyonu ABCA4 (%28.5) idi; bunu CRB1 (%10.7), MFSD8, RPE65 ve USH2A (her biri %7.1) takip etti. Diğer mutasyonlar arasında BEST1, LYST, MERTK, PDE, PROM1, RDH12, RHO (OPN2), RP9 ve SPATA7 (her biri %3.5) yer aldı. Elektrofizyoloji fonksiyonel karakterizasyonu destekledi; ancak, ileri periferik distrofide ERG yanıtları sıklıkla kaydedilemedi, bu da gruplar arasında niceliksel karşılaştırmaları sınırladı. OCT-A analizinde, santral retina distrofisi grubunda maküler yüzeyel damar yoğunluğu periferik gruba göre anlamlı derecede daha düşüktü (18.0±10.7 µm vs. 43.0±10.3 µm; p = 0.003). Optik sinir başı perfüzyonunda ise gruplar arasında anlamlı bir fark izlenmedi (tüm kadranlarda p > 0.05). Sonuç: KRD’li hastalar benzer klinik fenotiplerle başvursalar da, farklı genetik altyapılara ve oftalmik görüntüleme bulgularına sahip olabilirler.

Keywords

Elektroretinografi , Genetik Danışmanlık , Retina Distrofileri

Ethical Statement

Kurum: Balıkesir Üniversitesi Etik Kurulu Tarih: 08.12.2021 Onay numarası: 2021/268.

Supporting Institution

Yazarların beyan edecekleri herhangi bir finansal destek bulunmamaktadır.

Thanks

Yazarlar, bu çalışmaya katkıda bulunan herkese içten teşekkürlerini sunar.

References

• Acland, G. M., Aguirre, G. D., Ray, J., Zhang, Q., Aleman, T. S., Cideciyan, A. V., Pearce-Kelling, S. E., Anand, V., Zeng, Y., Maguire, A. M., Jacobson, S. G., Hauswirth, W. W. & Bennett, J. (2001). Gene therapy restores vision in a canine model of childhood blindness. Nature Genetics, 28(1), 92–95. https://doi.org/10.1038/NG0501-92
• Berson, E. L. (2007). Long-term visual prognoses in patients with retinitis pigmentosa: the Ludwig von Sallmann lecture. Experimental Eye Research, 85(1), 7–14. https://doi.org/10.1016/J.EXER.2007.03.001
• Campochiaro, P. A. & Mir, T. A. (2018). The mechanism of cone cell death in Retinitis Pigmentosa. Progress in Retinal and Eye Research, 62, 24–37. https://doi.org/10.1016/J.PRETEYERES.2017.08.004
• Cehajic-Kapetanovic, J., Xue, K., Martinez-Fernandez de la Camara, C., Nanda, A., Davies, A., Wood, L. J., Salvetti, A. P., Fischer, M. D., Aylward, J. W., Barnard, A. R., Jolly, J. K., Luo, E., Lujan, B. J., Ong, T., Girach, A., Black, G. C. M., Gregori, N. Z., Davis, J. L., Rosa, P. R., … MacLaren, R. E. (2020). Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nature Medicine, 26(3), 354–359. https://doi.org/10.1038/S41591-020-0763-1
• Diaconita, V., Kassotis, A. & Ngo, W. K. (2023). Optical Coherence Tomography Angiography (OCTA) Findings in Retinitis Pigmentosa. Methods in Molecular Biology (Clifton, N.J.), 2560, 101–109. https://doi.org/10.1007/978-1-0716-2651-1_9
• Fahim, A. (2018). Retinitis pigmentosa: recent advances and future directions in diagnosis and management. Current Opinion in Pediatrics, 30(6), 725–733. https://doi.org/10.1097/MOP.0000000000000690
• Fahim, A. T., Daiger, S. P. & Weleber, R. G. (2017). Nonsyndromic Retinitis Pigmentosa Overview. GeneReviews®. https://www.ncbi.nlm.nih.gov/books/NBK1417/
• Galan, A., Chizzolini, M., Milan, E., Sebastiani, A., Costagliola, C. & Parmeggiani, F. (2011). Good epidemiologic practice in retinitis pigmentosa: from phenotyping to biobanking. Current Genomics, 12(4), 260–266. https://doi.org/10.2174/138920211795860071
• Ganesh, A. & Keep, R. B. (2011). Genetic testing in retinal dystrophies. Oman Journal of Ophthalmology, 4(3), 105. https://doi.org/10.4103/0974-620X.91264
• Gersch, J., Hufendiek, K., Delarocque, J., Framme, C., Jacobsen, C., Stöhr, H., Kellner, U. & Hufendiek, K. (2022). Investigation of Structural Alterations in Inherited Retinal Diseases: A Quantitative SD-OCT-Analysis of Retinal Layer Thicknesses in Light of Underlying Genetic Mutations. International Journal of Molecular Sciences, 23(24). https://doi.org/10.3390/IJMS232416007/S1
• Giansanti, F., Vicini, G., Sodi, A., Nicolosi, C., Bellari, L., Virgili, G., Rizzo, S. & Bacherini, D. (2022). Optical Coherence Tomography Angiography for the Evaluation of Retinal and Choroidal Vasculature in Retinitis Pigmentosa: A Monocentric Experience. Diagnostics, 12(5). https://doi.org/10.3390/DIAGNOSTICS12051020
• Hamel, C. (2006). Retinitis pigmentosa. Orphanet Journal of Rare Diseases, 1(1), 1–12. https://doi.org/10.1186/1750-1172-1-40/FIGURES/3 Hanany, M., Rivolta, C. & Sharon, D. (2020). Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases. Proceedings of the National Academy of Sciences of the United States of America, 117(5), 2710–2716. https://doi.org/10.1073/PNAS.1913179117
• Hartong, D. T., Berson, E. L. & Dryja, T. P. (2006). Retinitis pigmentosa. Lancet (London, England), 368(9549), 1795–1809. https://doi.org/10.1016/S0140-6736(06)69740-7
• HH, S., JC, Z., SL, Y., JD, S., YS, W., JC, W., F, G. & L, C. (2022). A novel mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa. International Journal of Ophthalmology, 15(9), 1423–1430. https://doi.org/10.18240/IJO.2022.09.03
• Jacobson, S. G., Roman, A. J., Aleman, T. S., Sumaroka, A., Herrera, W., Windsor, E. A. M., Atkinson, L. A., Schwartz, S. B., Steinberg, J. D. & Cideciyan, A. V. (2010). Normal Central Retinal Function and Structure Preserved in Retinitis Pigmentosa. Investigative Ophthalmology & Visual Science, 51(2), 1079–1085. https://doi.org/10.1167/IOVS.09-4372
• Koenekoop, R. K. (2004). An overview of leber congenital amaurosis: A model to understand human retinal development. Survey of Ophthalmology, 49(4), 379–398. https://doi.org/10.1016/j.survophthal.2004.04.003
• Lubiński, W., Palacz, O. & Karczewicz, D. (2006). Electrophysiological tests in early and differential diagnosis of some hereditary retinal and optic nerve diseases. Klinika Oczna / Acta Ophthalmologica Polonica, 108(1), 93–98.
• Mata, N. L., Weng, J. & Travis, G. H. (2000). Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration. Proceedings of the National Academy of Sciences of the United States of America, 97(13), 7154–7159. https://doi.org/10.1073/PNAS.130110497/ASSET/8EFAD1AD-F3B4-4382-BA3E-E060B9622C38/ASSETS/GRAPHIC/PQ1301104005.JPEG
• Reddy, Rr., Venkateshwaramma, B., Babu, B. & Hymavathi, C. (2011). Silvery hair syndrome in two cousins: Chediak-Higashi syndrome vs Griscelli syndrome, with rare associations. International Journal of Trichology, 3(2), 107. https://doi.org/10.4103/0974-7753.90825
• Rezaei, K. A., Zhang, Q., Chen, C. L., Chao, J. & Wang, R. K. (2017). Retinal and choroidal vascular features in patients with retinitis pigmentosa imaged by OCT based microangiography. Graefe’s Archive for Clinical and Experimental Ophthalmology = Albrecht von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie, 255(7), 1287–1295. https://doi.org/10.1007/S00417-017-3633-X
• Shen, C., Li, Y., Wang, Q., Chen, Y. N., Li, W. & Wei, W. Bin. (2020). Choroidal vascular changes in retinitis pigmentosa patients detected by optical coherence tomography angiography. BMC Ophthalmology, 20(1), 1–8. https://doi.org/10.1186/S12886-020-01640-5/TABLES/4
• Skorczyk-Werner, A., Sowińska-Seidler, A., Wawrocka, A., Walczak-Sztulpa, J. & Krawczyński, M. R. (2023). Molecular background of Leber congenital amaurosis in a Polish cohort of patients-novel variants discovered by NGS. Journal of Applied Genetics, 64(1). https://doi.org/10.1007/S13353-022-00733-9
• Talib, M. & Boon, C. J. F. (2020). Retinal dystrophies and the road to treatment: Clinical requirements and considerations. Asia-Pacific Journal of Ophthalmology, 9(3), 159–179. https://doi.org/10.1097/APO.0000000000000290
• Tatour, Y. & Ben-Yosef, T. (2020). Syndromic Inherited Retinal Diseases: Genetic, Clinical and Diagnostic Aspects. Diagnostics 2020, Vol. 10, Page 779, 10(10), 779. https://doi.org/10.3390/DIAGNOSTICS10100779
• Tee, J. J. L., Smith, A. J., Hardcastle, A. J. & Michaelides, M. (n.d.). Title: RPGR-associated Retinopathy-Clinical Features, Molecular Genetics, Animal Models and Therapeutic Options.
• Verbakel, S. K., van Huet, R. A. C., Boon, C. J. F., den Hollander, A. I., Collin, R. W. J., Klaver, C. C. W., Hoyng, C. B., Roepman, R. & Klevering, B. J. (2018). Non-syndromic retinitis pigmentosa. Progress in Retinal and Eye Research, 66, 157–186. https://doi.org/10.1016/J.PRETEYERES.2018.03.005