Stargardt Disease. Literature review
https://doi.org/10.18008/1816-5095-2026-1-7-13
Abstract
This literature review is devoted to the most common hereditary disease of the retina, called Stargardt disease. The work provides information on the epidemiology, molecular genetics, and pathophysiology of this disease. Clinical forms of Stargardt disease are described in details. Special attention is paid to a multimodal approach using modern visualization methods, such as retinal optical coherence tomography, autofluorescence study, which allow differential diagnostics with diseases such as retinal pattern dystrophies, autosomal dominant Stargardt-like macular dystrophies STGD3 and STGD4, neuronal ceroid lipofuscinosis. The article presents information on potential treatment methods for patients with Stargardt disease aimed at either reducing lipofuscin accumulation in retinal pigment epithelium cells or delivering the normal ABCA4 gene to the eye.
About the Authors
R. S. Zhazybaev
The Khabarovsk Branch of the S. Fyodorov Eye Microsurgery Federal State Institution
Russian Federation
Russian Federation
Zhazybaev Ruslan S., ophthalmologist of the Consultative and Diagnostic Department
Tikhookeanskaya str., 211, Khabarovsk, 680033
A. L. Zhirov
The Khabarovsk Branch of the S. Fyodorov Eye Microsurgery Federal State Institution
Russian Federation
Russian Federation
Zhirov Arkadiy L., Head of the Consultative and Diagnostic Department, ophthalmologist
Tikhookeanskaya str., 211, Khabarovsk, 680033
References
1. Stargardt K. Über familliäre, progressive Degeneration in der Maculagegend des Auges. Graefes Arch Clin Exp Ophthalmol. 1909;71:534–550. doi: 10.1007/BF01961301.
2. Tanna P, Strauss RW, Fujinami K, Michaelides M. Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options. Br J Ophthalmol. 2017;101(1):25–30. doi: 10.1136/bjophthalmol‑2016‑308823.
3. Zol’nikova IV, Ivanova ME, Strel’nikov VV, Levina DV, Demenkova ON, Tanas AS, Rogatina EV, Egorova IV, Rogova SYu, Prikazyuk EYu. The spectrum of mutations in the patients presenting with ABCA4‑associated stargardt’s disease in a Russian population. Russian pediatric ophthalmology. 2016;11(1):14–22 (In Russ.). doi: 10.18821/1993‑1859‑2016‑11‑1‑14‑22.
4. Cremers FPM, Lee W, Collin RWJ, Allikmets R. Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations. Prog Retin Eye Res. 2020;79:100861. doi: 10.1016/j.preteyeres.2020.100861.
5. Klevering BJ, Deutman AF, Maugeri A, Cremers FP, Hoyng CB. The spectrum of retinal phenotypes caused by mutations in the ABCA4 gene. Graefes Arch Clin Exp Ophthalmol. 2005;243(2):90–100. doi: 10.1007/s00417‑004‑1079‑4.
6. Sparrow JR, Gregory‑Roberts E, Yamamoto K, Blonska A, Ghosh SK, Ueda K, Zhou J. The bisretinoids of retinal pigment epithelium. Prog Retin Eye Res. 2012;31(2):121–135. doi: 10.1016/j.preteyeres.2011.12.001.
7. Delori FC, Dorey CK, Staurenghi G, Arend O, Goger DG, Weiter JJ. In vivo fl orescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci. 1995;36(3):718–729.
8. Charbel Issa P, Barnard AR, Singh MS, Carter E, Jiang Z, Radu RA, Schraermeyer U, MacLaren RE. Fundus autofluorescence in the Abca4(‑/‑) mouse model of Stargardt disease correlation with accumulation of A2E, retinal function, and histology. Invest Ophthalmol Vis Sci. 2013;54(8):5602–5612. doi: 10.1167/iovs.13‑11688.
9. Franceschetti A. A special form of tapetoretinal degeneration: fundus fl avimaculatus. Trans Am Acad Opthalmol Otolaryngol. 1965;69(6):1048–1053.
10. Fujinami K, Zernant J, Chana RK, Wright GA, Tsunoda K, Ozawa Y, Tsubota K, Robson AG, Holder GE, Allikmets R, Michaelides M, Moore AT. Clinical and molecular characteristics of childhood‑onset Stargardt disease. Ophthalmology. 2015;122(2):326–334. doi: 10.1016/j.ophtha.2014.08.012.
11. Lee W, Nõupuu K, Oll M, Duncker T, Burke T, Zernant J, Bearelly S, Tsang SH, Sparrow JR, Allikmets R. The external limiting membrane in early‑onset Stargardt disease. Invest Ophthalmol Vis Sci. 2014;55(10):6139–6149. doi: 10.1167/iovs.14‑15126.
12. Nõupuu K, Lee W, Zernant J, Tsang SH, Allikmets R. Structural and genetic assessment of the ABCA4‑associated optical gap phenotype. Invest Ophthalmol Vis Sci. 2014;55(11):7217–7226. doi: 10.1167/iovs.14‑14674.
13. Fujinami K, Sergouniotis PI, Davidson AE, Wright G, Chana RK, Tsunoda K, Tsubota K, Egan CA, Robson AG, Moore AT, Holder GE, Michaelides M, Webster AR. Clinical and molecular analysis of Stargardt disease with preserved foveal structure and function. Am J Ophthalmol. 2013;156(3):487–501.e1. doi: 10.1016/j.ajo.2013.05.003.
14. Rotenstreich Y, Fishman GA, Anderson RJ. Visual acuity loss and clinical observations in a large series of patients with Stargardt disease. Ophthalmology. 2003;110(6):1151–1158. doi: 10.1016/S0161‑6420(03)00333‑6.
15. Schönbach EM, Wolfson Y, Strauss RW, Ibrahim MA, Kong X, Muñoz B, Birch DG, Cideciyan AV, Hahn GA, Nittala M, Sunness JS, Sadda SR, West SK, Scholl HPN; ProgStar Study Group. Macular Sensitivity Measured With Microperimetry in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 7. JAMA Ophthalmol. 2017;135(7):696–703. doi: 10.1001/jamaophthalmol.2017.1162.
16. Schroeder M, Kjellström U. Full‑field ERG as a predictor of the natural course of ABCA4‑associated retinal degenerations. Mol Vis. 2018;24:1–16.
17. Lambertus S, van Huet RA, Bax NM, Hoefsloot LH, Cremers FP, Boon CJ, Klevering BJ, Hoyng CB. Early‑onset stargardt disease: phenotypic and genotypic characteristics. Ophthalmology. 2015;122(2):335–344. doi: 10.1016/j.ophtha.2014.08.032.
18. Fishman GA. Fundus flavimaculatus. A clinical classification. Arch Ophthalmol. 1976;94(12):2061–2067. doi: 10.1001/archopht.1976.03910040721003.
19. Noble KG, Carr RE. Stargardt’s disease and fundus flavimaculatus. Arch Ophthalmol. 1979;97(7):1281–1285. doi: 10.1001/archopht.1979.01020020023005.
20. Arrigo A, Grazioli A, Romano F, Aragona E, Bordato A, di Nunzio C, Sperti A, Bandello F, Battaglia Parodi M. Choroidal Patterns in Stargardt Disease: Correlations with Visual Acuity and Disease Progression. J Clin Med. 2019;8(9):1388. doi: 10.3390/jcm8091388.
21. Fujinami K, Lois N, Mukherjee R, McBain VA, Tsunoda K, Tsubota K, Stone EM, Fitzke FW, Bunce C, Moore AT, Webster AR, Michaelides M. A longitudinal study of Stargardt disease: quantitative assessment of fundus autofluorescence, progression, and genotype correlations. Invest Ophthalmol Vis Sci. 2013;54(13):8181– 8190. doi: 10.1167/iovs.13‑12104.
22. Kuehlewein L, Hariri AH, Ho A, Dustin L, Wolfson Y, Strauss RW, Scholl HP, Sadda SR. Comparison of manual and semiautomated fundus autofluorescence analysis of macular atrophy in Stargardt disease phenotype. Retina. 2016;36(6):1216– 1221. doi: 10.1097/IAE.0000000000000870.
23. Strauss RW, Muñoz B, Ho A, Jha A, Michaelides M, Mohand‑Said S, Cideciyan AV, Birch D, Hariri AH, Nittala MG, Sadda S, Scholl HPN; ProgStar Study Group. Incidence of Atrophic Lesions in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 5. JAMA Ophthalmol. 2017;135(7):687–695. doi: 10.1001/jamaophthalmol.2017.1121.
24. Klufas MA, Tsui I, Sadda SR, Hosseini H, Schwartz SD. Ultrawidefield autofl oresence in ABCA4 Stargardt disease. Retina. 2018;38(2):403–415. doi: 10.1097/IAE.0000000000001567.
25. Delori F, Greenberg JP, Woods RL, Fischer J, Duncker T, Sparrow J, Smith RT. Quantitative measurements of autofluorescence with the scanning laser ophthalmoscope. Invest Ophthalmol Vis Sci. 2011;52(13):9379–9390. doi: 10.1167/iovs.11‑8319.
26. Sheremet NL, Ronzina IA, Zhorzholadze NV, Strel’nikov VV. Relationship between structural and functional changes in retina in Stargardt disease. Russian Annals of Ophthalmology. 2016;132(3):42–48 (In Russ.). doi: 10.17116/oftalma2016132342‑48.
27. Khan KN, Kasilian M, Mahroo OAR, Tanna P, Kalitzeos A, Robson AG, Tsunoda K, Iwata T, Moore AT, Fujinami K, Michaelides M. Early Patterns of Macular Degeneration in ABCA4‑Associated Retinopathy. Ophthalmology. 2018;125(5):735–746. doi: 10.1016/j.ophtha.2017.11.020.
28. Querques G, Leveziel N, Benhamou N, Voigt M, Soubrane G, Souied EH. Analysis of retinal flecks in fundus flavimaculatus using optical coherence tomography. Br J Ophthalmol. 2006;90(9):1157–1162. doi: 10.1136/bjo.2006.094136.
29. Cai CX, Light JG, Handa JT. Quantifying the Rate of Ellipsoid Zone Loss in Stargardt Disease. Am J Ophthalmol. 2018;186:1–9. doi: 10.1016/j.ajo.2017.10.032.
30. Pang CE, Suqin Y, Sherman J, Freund KB. New insights into Stargardt disease with multimodal imaging. Ophthalmic Surg Lasers Imaging Retina. 2015;46(2):2579– 2561. doi: 10.3928/23258160‑20150213‑09.
31. Piri N, Nesmith BL, Schaal S. Choroidal hyperreflective foci in Stargardt disease shown by spectral‑domain optical coherence tomography imaging: correlation with disease severity. JAMA Ophthalmol. 2015;133(4):398–405. doi: 10.1001/jamaophthalmol.2014.5604.
32. Gomes NL, Greenstein VC, Carlson JN, Tsang SH, Smith RT, Carr RE, Hood DC, Chang S. A comparison of fundus autofluorescence and retinal structure in patients with Stargardt disease. Invest Ophthalmol Vis Sci. 2009;50(8):3953–3959. doi: 10.1167/iovs.08‑2657.
33. Van Huet RA, Bax NM, Westeneng‑Van Haaften SC, Muhamad M, ZonneveldVrieling MN, Hoefsloot LH, Cremers FP, Boon CJ, Klevering BJ, Hoyng CB. Foveal sparing in Stargardt disease. Invest Ophthalmol Vis Sci. 2014;55(11):7467–7478. doi: 10.1167/iovs.13‑13825.
34. Lois N, Holder GE, Bunce C, Fitzke FW, Bird AC. Phenotypic subtypes of Stargardt macular dystrophy‑fundus flavimaculatus. Arch Ophthalmol. 2001;119(3):359– 369. doi: 10.1001/archopht.119.3.359.
35. Jayasundera T, Rhoades W, Branham K, Niziol LM, Musch DC, Heckenlively JR. Peripapillary dark choroid ring as a helpful diagnostic sign in advanced stargardt disease. Am J Ophthalmol. 2010;149(4):656–660.e2. doi: 10.1016/j.ajo.2009.11.005.
36. Marmor MF, Byers B. Pattern dystrophy of the pigment epithelium. Am J Ophthalmol. 1977;84(1):32–44. doi: 10.1016/0002‑9394(77)90320‑8.
37. Francis PJ, Schultz DW, Gregory AM, Schain MB, Barra R, Majewski J, Ott J, Acott T, Weleber RG, Klein ML. Genetic and phenotypic heterogeneity in pattern dystrophy. Br J Ophthalmol. 2005;89(9):1115–1119. doi: 10.1136/bjo.2004.062695.
38. Cibis GW, Morey M, Harris DJ. Dominantly inherited macular dystrophy with flecks (Stargardt). Arch Ophthalmol. 1980;98(10):1785–1789. doi: 10.1001/archopht.1980.01020040637010.
39. Kniazeva MF, Chiang MF, Cutting GR, Zack DJ, Han M, Zhang K. Clinical and genetic studies of an autosomal dominant cone‑rod dystrophy with features of Stargardt disease. Ophthalmic Genet. 1999;20(2):71–81. doi: 10.1076/opge.20.2.71.2287.
40. Palejwala NV, Gale MJ, Clark RF, Schlechter C, Weleber RG, Pennesi ME. Insights into autosomal dominant Stargardt‑like macular dystrophy through multimodality diagnostic imaging. Retina. 2016;36(1):119–130. doi: 10.1097 IAE.0000000000000659.
41. Kraeva LS, Koroleva ES, Alifirova VM, Kuzmina AV. A clinical case of neuronal ceroid lipofuscinosis type 2. Bulletin of Siberian Medicine. 2019;18(4):244–248 (In Russ.). doi: 10.20538/1682‑0363‑2019‑4‑244‑248.
42. Westeneng‑van Haaften SC, Boon CJ, Cremers FP, Hoefsloot LH, den Hollander AI, Hoyng CB. Clinical and genetic characteristics of late‑onset Stargardt’s disease. Ophthalmology. 2012;119(6):1199–1210. doi: 10.1016/j.ophtha.2012.01.005.
43. Zhorzholadze NV, Sheremet NL, Tanas AS, Strelnikov VV. New possibilities in the treatment of Stargardt disease. Russian Annals of Ophthalmology. 2020;136(4):333– 343 (In Russ.). doi: 10.17116/oftalma2020136042333.
44. Federspiel CA, Bertelsen M, Kessel L. Vitamin A in Stargardt disease‑an evidence‑based update. Ophthalmic Genet. 2018;39(5):555–559. doi: 10.1080/13816810.2018.1488174.
45. Battaglia Parodi M, Munk MR, Iacono P, Bandello F. Ranibizumab for subfoveal choroidal neovascularisation associated with Stargardt disease. Br J Ophthalmol. 2015;99(9):1268–1270. doi: 10.1136/bjophthalmol‑2014‑305783.
46. Baibarin KA, Katargina LA. Electronic video magnifiers as a low‑vision aid for patients with Stargardt disease. Russian Pediatric Ophthalmology. 2022;17(1):25–31 (In Russ.). doi: 10.17816/rpoj91130.
47. Huang D, Heath Jeffery RC, Aung‑Htut MT, McLenachan S, Fletcher S, Wilton SD, Chen FK. Stargardt disease and progress in therapeutic strategies. Ophthalmic Genet. 2022;43(1):1–26. doi: 10.1080/13816810.2021.1966053.
48. Trapani I, Toriello E, de Simone S, Colella P, Iodice C, Polishchuk EV, Sommella A, Colecchi L, Rossi S, Simonelli F, Giunti M, Bacci ML, Polishchuk RS, Auricchio A. Improved dual AAV vectors with reduced expression of truncated proteins are safe and effective in the retina of a mouse model of Stargardt disease. Hum Mol Genet. 2015;24(23):6811–6825. doi: 10.1093/hmg/ddv386.
49. Grandinetti AA, Portella E, Arana J, Iskorostenski NT. Subretinal fibrosis in Stargardt’s disease: case report. Arq Bras Oftalmol. 2011;74(6):449–451. doi: 10.1590/s0004‑27492011000600015.
50. Volodin PL, Pedanova EK, Matyaeva AD, Poroshina MA. Inactive macular neovascularization in Stargardt’s disease. Ophthalmology Reports. 2023;16(3):83–88 (In Russ.). doi: 10.17816/OV321387.
Review
For citations:
Zhazybaev R.S., Zhirov A.L. Stargardt Disease. Literature review. Ophthalmology in Russia. 2026;23(1):7-13. (In Russ.) https://doi.org/10.18008/1816-5095-2026-1-7-13
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