Sorsby's fundus dystrophy: a systematic review_Chinese Journal of Ocular Fundus Diseases

Authors：

Gu Qiumei ¹ , Chen Zhengju ² , Xiao Lin ³ , Yang Zhibo ⁴ ,  Liu Longqian ¹

1. Department of Optometry & Visual Science, West China Hospital of Sichuan University, Chengdu 610041, China;
2. Huaxi MR Research Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China;
3. Department of pathology Institute of Clinical Pathology, West China Hospital, Sichuan University, Chengdu 610000, China;
4. Department of Evidence Based Nursing Center, West China Hospital of Sichuan University, Chengdu 610041, China;

Corresponding author：

Liu Longqian, Email: b.q15651@hotmail.com

Keywords：

Sorsby fundus dystrophy; Choroidal neovascularization gene; Angiogenesis inhibitors; Genes; Mutation; TIMP3 gene

DOI：

10.3760/cma.j.cn511434-20220614-00359

Video：

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Objective To conduct a systematic review of clinical manifestations, treatment, and associated genotyping of Sorsby fundus dystrophy (SFD). Methods An evidence-based medicine study. Sorsby fundus dystrophy, anti-vascular endothelial growth factor therapy, choroidal neovascularization, macular neovascularization, and TIMP3 gene were hereby used as search terms. Relevant literature was searched in CNKI, Wanfang, PubMed of the National Library of Medicine, and Embase of the Netherlands. The time span for literature searching ranged from the establishment of the database to April 2022, and two reviewers independently screened the literature and extracted relevant data, with duplicates, incomplete or irrelevant articles, and review articles excluded. SPSS26.0 software was used for analysis. The 95% confidence interval (CI) was used as an estimate of the effect size. The clinical manifestations, treatment and related pathogenic genes of SFD were counted and recorded. Results According to the search strategy, 157 pieces of literature were initially retrieved, and 49 eyes of 35 patients from 16 articles were finally included for analysis, among which, 17 patients were male, 13 patients were female, and 5 patients were unknown gender; 16 involved left eyes, 19 involved right eyes, and 14 involved unidentified eyes. The age of the disease onset was 42.33±2.19 years (28-59) years old. There were 19 cases with a positive family history, and the total positive rate was 54.3% (19/35, 95%CI 36%-72%). There were 31 cases of gene mutation, all of which were TIMP3. In the included literature, there were 2 and 2 cases with no mutation and unreported loci, respectively, with a total positive rate of 93.9% (31/33, 95%CI 85%-100%). Among the 31 cases with gene mutation, 22, 4, 1, and 4 cases were in the UK, Germany, Switzerland, and Chinese, respectively, and the detection rates were all 100% (22/22, 4/4, 1/1, 4/4). The clinical manifestations of SFD were mainly yellow-white deposits in the fundus and choroidal neovascularization (CNV) in the macula, thereby leading to a decrease in central vision, followed by the expansion of the deposits to the periphery, the further development of CNV, and a severe decline in vision caused by peripheral retinal and choroidal atrophy. The treatment methods for SFD include photodymatic therapy, anti-VEGF drugs, glucocorticoids, vitamin A, etc., among which, anti-VEGF drugs were considered the first-line treatment, and the combined treatment was provided with a better prognosis than a single treatment. Conclusions Variations in the TIMP3 gene cause SFD, the fundus characteristic manifestations of which, are yellowish-white deposits and CNV, which develop from the center to the periphery, thus resulting in progressive decline of visual acuity. Current studies have shown that combined therapy presents a better prognosis than monotherapy.

Citation： Gu Qiumei, Chen Zhengju, Xiao Lin, Yang Zhibo, Liu Longqian. Sorsby's fundus dystrophy: a systematic review. Chinese Journal of Ocular Fundus Diseases, 2022, 38(11): 925-930. doi: 10.3760/cma.j.cn511434-20220614-00359 Copy

1.	Capon MR, Polkinghorne PJ, Fitzke FW, et al. Sorsby's pseudoinflammatory macula dystrophy: Sorsby's fundus dystrophies[J]. Eye, 1988, 2(Pt 1): 114-122. DOI: 10.1038/eye.1988.23.
2.	郭丽莉, 黎晓新, 梁建宏. Sorsby眼底营养不良[J]. 国际眼科纵览, 2006, 30(3): 156-158. DOI: 10.3760/cma.j.issn.1673-5803.2006.03.004.Guo LL, Li XX, Liang JH. Sorsby's fundus dystrophy[J]. Int Rev Ophthalmol, 2006, 30(3): 156-158. DOI: 10.3760/cma.j.issn.1673-5803.2006.03.004.
3.	Jacobson SG, Cideciyan AV, Bennett J, et al. Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy[J]. Arch Ophthalmol, 2002, 120(3): 376-379. DOI: 10.1001/archopht.120.3.376.
4.	Sivaprasad S, Webster AR, Egan C, et al. Clinical course and treatment outcomes of Sorsby fundus dystrophy[J]. Am J Ophthalmol, 2008, 146(2): 228-234. DOI: 10.1016/j.ajo.2008.03.024.
5.	尹小芳, 叶祖科, 汤秀容, 等. Sorsby眼底营养不良一家系[J]. 中华眼底病杂志, 2018, 34(6): 546-551. DOI: 10.3760/cma.j.issn.1005-1015.2018.06.005.Yin XF, Ye ZK, Tang XR, et al. A pedigree of Sorsby fundus dystrophy with mutation in TIMP3 gene[J]. Chin J Ocul Fundus Dis, 2018, 34(6): 546-551. DOI: 10.3760/cma.j.issn.1005-1015.2018.06.005.
6.	Rahman N, Georgiou M, Khan KN, et al. Macular dystrophies: clinical and imaging features, molecular genetics and therapeutic options[J]. Br J Ophthalmol, 2020, 104(4): 451-460. DOI: 10.1136/bjophthalmol-2019-315086.
7.	Fung AT, Stöhr H, Weber BHF, et al. Atypical sorsby fundus dystrophy with a novel Tyr159cys Timp-3 mutation[J]. Retin Cases Brief Rep, 2013, 7(1): 71-74. DOI: 10.1097/ICB.0b013e318267101e.
8.	Gliem M, Müller PL, Mangold E, et al. Sorsby fundus dystrophy: novel mutations, novel phenotypic characteristics, and treatment outcomes[J]. Invest Ophthalmol Vis Sci, 2015, 56(4): 2664-2676. DOI: 10.1167/iovs.14-15733.
9.	Jacobson SG, Cideciyan AV, Regunath G, et al. Night blindness in Sorsby's fundus dystrophy reversed by vitamin A[J]. Nat Genet, 1995, 11(1): 27-32. DOI: 10.1038/ng0995-27.
10.	Weber BH, Vogt G, Wolz W, et al. Sorsby's fundus dystrophy is genetically linked to chromosome 22q13-qter[J]. Nature Genet, 1994, 7(2): 158-161. DOI: 10.1038/ng0694-158.
11.	Christensen DRG, Brown FE, Cree AJ, et al. Sorsby fundus dystrophy-a review of pathology and disease mechanisms[J]. Exp Eye Res, 2017, 165: 35-46. DOI: 10.1016/j.exer.2017.08.014.
12.	Felbor U, Stöhr H, Amann T, et al. A novel Ser156Cys mutation in the tissue inhibitor of metalloproteinases-3 (TIMP3) in Sorsby's fundus dystrophy with unusual clinical features[J]. Hum Mol Genet, 1995, 4(12): 2415-2416. DOI: 10.1093/hmg/4.12.2415.
13.	Carrero-Valenzuela RD, Klein ML, Weleber RG, et al. Sorsby fundus dystrophy. A family with the Ser181Cys mutation of the tissue inhibitor of metalloproteinases 3[J]. Arch Ophthalmol, 1996, 114(6): 737-738. DOI: 10.1001/archopht.1996.01100130729016.
14.	Felbor U, Stöhr H, Amann T, et al. A second independent Tyr168Cys mutation in the tissue inhibitor of metalloproteinases-3(TIMP3) in Sorsby's fundus dystrophy[J]. J Med Genet, 1996, 33(3): 233-236. DOI: 10.1136/jmg.33.3.233.
15.	Bakall B, Sohn EH, Riley J, et al. Novel mutations and change ofnomenclature for pathogen icvariants in the TIMP3 gene causing Sorsby fundus dystrophy[J/OL]. Invest Ophthalmol Vis Sci, 2014, 55: 3290[2014-04-01]. https://iovs.arvojournals.org/article.aspx?articleid=2268700.
16.	Schoenberger SD, Agarwal A. A novel mutation at the N-terminaldomain of the TIMP3 gene in Sorsby fundus dystrophy[J]. Retina, 2013, 33(2): 429-435. DOI: 10.1097/IAE.0b013e318263d3b4.
17.	Saihan Z, Li Z, Rice J, et al. Clinical and biochemical effects of the E139K missense mutation in the TIMP3 gene, associated with Sorsby fundus dystrophy[J]. Mol Vis, 2009, 15: 1218-1230.
18.	Langton KP, McKie N, Curtis A, et al. A novel tissue inhibitor of metalloproteinases-3 mutation reveals a common molecular phenotype in Sorsby's fundus dystrophy[J]. J Biol Chem, 2000, 275(35): 27027-27031. DOI: 10.1074/jbc.M909677199.
19.	Barbazetto IA, Hayashi M, Klais CM, et al. A novel TIMP3 mutation associated with Sorsby fundus dystrophy[J]. Arch Ophthalmol, 2005, 123(4): 542-543. DOI: 10.1001/archopht.123.4.542.
20.	Baston A, Gerhardt C, Zandi S, et al. Visual outcome after Intravitreal anti-VEGF therapy for macular neovascularisation secondary to Sorsby's fundus dystrophy: a systematic review[J/OL]. J Clin Med, 2021, 10(11): 2433[2021-05-30]. https://pubmed.ncbi.nlm.nih.gov/34070857/. DOI: 10.3390/jcm10112433.
21.	Gemenetzi MK, Luff AJ, Lotery AJ. Successful treatment of choroidal neovascularization secondary to Sorsby fundus dystrophy with intravitreal Bevacizumab[J]. Retin Cases Brief Rep, 2011, 5(2): 132-135. DOI: 10.1097/ICB.0b013e3181cc216b.
22.	Gray TL, Wong HC, Raymond GL. Choroidal neovascularization secondary to Sorsby fundus dystrophy treated with intravitreal Bevacizumab[J]. Retin Cases Brief Rep, 2012, 6(2): 193-196. DOI: 10.1097/ICB.0b013e31822476fd.
23.	Balaskas K, Hovan M, Mahmood S, et al. Ranibizumab for the management of Sorsby fundus dystrophy[J]. Eye, 2013, 27(1): 101-102. DOI: 10.1038/eye.2012.221.
24.	Copete-Piqueras S, Cava-Valenciano C, Flores-Moreno I, et al. Tratamiento antiangiogénico en fondo de distrofia de Sorsby sin mutación en gen de TIMP-3[J]. Arch Soc Españ ola Oftalmol, 2013, 88(6): 240-243. DOI: 10.1016/j.oftal.2011.12.005.
25.	Kapoor KG, Bakri SJ. Intravitreal anti-vascular endothelial growth factor therapy for choroidal neovascularization due to Sorsby macular dystrophy[J]. J Ocul Pharmacol Ther, 2013, 29(4): 444-447. DOI: 10.1089/jop.2011.0206.
26.	Keller J, Giralt J, Alforja S, et al. Altering the clinical course of Sorsby fundus dystrophy with the use of anti-vascular endothelial growth factor intraocular therapy[J]. Retin Cases Brief Rep, 2015, 9(2): 104-105. DOI: 10.1097/ICB.0000000000000103.
27.	Mohla A, Khan K, Kasilian M, et al. OCT angiography in the management of choroidal neovascular membrane secondary to Sorsby fundus dystrophy[J/OL]. BMJ Case Rep, 2016, 2016: bcr2016216453[2016-09-01]. https://casereports.bmj.com/content/2016/bcr-2016-216453.long. DOI: 10.1136/bcr-2016-216453.
28.	Menassa N, Burgula S, Empeslidis T, et al. Bilateral choroidal neovascular membrane in a young patient with Sorsby fundus dystrophy: the value of prompt treatment[J/OL]. BMJ Case Rep, 2017, 2017: bcr2017220488[2017-08-03]. https://pubmed.ncbi.nlm.nih.gov/28775088/. DOI: 10.1136/bcr-2017-220488.
29.	Tsokolas G, Almuhtaseb H, Lotery A. Evaluation of Pro-re-Nata (PRN) and treat and extend Bevacizumab treatment protocols in Sorsby fundus dystrophy[J]. Eur J Ophthalmol, 2018, 30(1): 26-33.
30.	Kaye R, Lotery A. Long-term outcome of Bevacizumab therapy in Sorsby fundus dystrophy, a case series[J]. Investig Ophthalmol Vis Sci, 2017, 58: 229.
31.	Sanz GF, Alonso-Gonzalez R, Keane P, et al. Treatment with intravitreal an-ti-VEGF for choroidal neovascular membrane secondary to Sorsby's fundus dystrophy: a 24-month analysis[J/OL]. Invest Ophthal Vis Sci, 2013, 54: 3863[2013-06-01]. https://iovs.arvojournals.org/article.aspx?articleid=2148681.
32.	Hoskin A, Sehmi K, Bird AC. Sorsby's pseudoinflammatory macular dystrophy[J]. Brit J Ophthal, 1981, 65(12): 859-865. DOI: 10.1136/bjo.65.12.859.
33.	Klenotic PA, Munier FL, Marmorstein LY, et al. Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of epithelial growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1). Implications for macular degenerations[J]. J Biol Chem, 2004, 279(29): 30469-30473. DOI: 10.1074/jbc.M403026200.

1. Capon MR, Polkinghorne PJ, Fitzke FW, et al. Sorsby's pseudoinflammatory macula dystrophy: Sorsby's fundus dystrophies[J]. Eye, 1988, 2(Pt 1): 114-122. DOI: 10.1038/eye.1988.23.
2. 郭丽莉, 黎晓新, 梁建宏. Sorsby眼底营养不良[J]. 国际眼科纵览, 2006, 30(3): 156-158. DOI: 10.3760/cma.j.issn.1673-5803.2006.03.004.Guo LL, Li XX, Liang JH. Sorsby's fundus dystrophy[J]. Int Rev Ophthalmol, 2006, 30(3): 156-158. DOI: 10.3760/cma.j.issn.1673-5803.2006.03.004.
3. Jacobson SG, Cideciyan AV, Bennett J, et al. Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy[J]. Arch Ophthalmol, 2002, 120(3): 376-379. DOI: 10.1001/archopht.120.3.376.
4. Sivaprasad S, Webster AR, Egan C, et al. Clinical course and treatment outcomes of Sorsby fundus dystrophy[J]. Am J Ophthalmol, 2008, 146(2): 228-234. DOI: 10.1016/j.ajo.2008.03.024.
5. 尹小芳, 叶祖科, 汤秀容, 等. Sorsby眼底营养不良一家系[J]. 中华眼底病杂志, 2018, 34(6): 546-551. DOI: 10.3760/cma.j.issn.1005-1015.2018.06.005.Yin XF, Ye ZK, Tang XR, et al. A pedigree of Sorsby fundus dystrophy with mutation in TIMP3 gene[J]. Chin J Ocul Fundus Dis, 2018, 34(6): 546-551. DOI: 10.3760/cma.j.issn.1005-1015.2018.06.005.
6. Rahman N, Georgiou M, Khan KN, et al. Macular dystrophies: clinical and imaging features, molecular genetics and therapeutic options[J]. Br J Ophthalmol, 2020, 104(4): 451-460. DOI: 10.1136/bjophthalmol-2019-315086.
7. Fung AT, Stöhr H, Weber BHF, et al. Atypical sorsby fundus dystrophy with a novel Tyr159cys Timp-3 mutation[J]. Retin Cases Brief Rep, 2013, 7(1): 71-74. DOI: 10.1097/ICB.0b013e318267101e.
8. Gliem M, Müller PL, Mangold E, et al. Sorsby fundus dystrophy: novel mutations, novel phenotypic characteristics, and treatment outcomes[J]. Invest Ophthalmol Vis Sci, 2015, 56(4): 2664-2676. DOI: 10.1167/iovs.14-15733.
9. Jacobson SG, Cideciyan AV, Regunath G, et al. Night blindness in Sorsby's fundus dystrophy reversed by vitamin A[J]. Nat Genet, 1995, 11(1): 27-32. DOI: 10.1038/ng0995-27.
10. Weber BH, Vogt G, Wolz W, et al. Sorsby's fundus dystrophy is genetically linked to chromosome 22q13-qter[J]. Nature Genet, 1994, 7(2): 158-161. DOI: 10.1038/ng0694-158.
11. Christensen DRG, Brown FE, Cree AJ, et al. Sorsby fundus dystrophy-a review of pathology and disease mechanisms[J]. Exp Eye Res, 2017, 165: 35-46. DOI: 10.1016/j.exer.2017.08.014.
12. Felbor U, Stöhr H, Amann T, et al. A novel Ser156Cys mutation in the tissue inhibitor of metalloproteinases-3 (TIMP3) in Sorsby's fundus dystrophy with unusual clinical features[J]. Hum Mol Genet, 1995, 4(12): 2415-2416. DOI: 10.1093/hmg/4.12.2415.
13. Carrero-Valenzuela RD, Klein ML, Weleber RG, et al. Sorsby fundus dystrophy. A family with the Ser181Cys mutation of the tissue inhibitor of metalloproteinases 3[J]. Arch Ophthalmol, 1996, 114(6): 737-738. DOI: 10.1001/archopht.1996.01100130729016.
14. Felbor U, Stöhr H, Amann T, et al. A second independent Tyr168Cys mutation in the tissue inhibitor of metalloproteinases-3(TIMP3) in Sorsby's fundus dystrophy[J]. J Med Genet, 1996, 33(3): 233-236. DOI: 10.1136/jmg.33.3.233.
15. Bakall B, Sohn EH, Riley J, et al. Novel mutations and change ofnomenclature for pathogen icvariants in the TIMP3 gene causing Sorsby fundus dystrophy[J/OL]. Invest Ophthalmol Vis Sci, 2014, 55: 3290[2014-04-01]. https://iovs.arvojournals.org/article.aspx?articleid=2268700.
16. Schoenberger SD, Agarwal A. A novel mutation at the N-terminaldomain of the TIMP3 gene in Sorsby fundus dystrophy[J]. Retina, 2013, 33(2): 429-435. DOI: 10.1097/IAE.0b013e318263d3b4.
17. Saihan Z, Li Z, Rice J, et al. Clinical and biochemical effects of the E139K missense mutation in the TIMP3 gene, associated with Sorsby fundus dystrophy[J]. Mol Vis, 2009, 15: 1218-1230.
18. Langton KP, McKie N, Curtis A, et al. A novel tissue inhibitor of metalloproteinases-3 mutation reveals a common molecular phenotype in Sorsby's fundus dystrophy[J]. J Biol Chem, 2000, 275(35): 27027-27031. DOI: 10.1074/jbc.M909677199.
19. Barbazetto IA, Hayashi M, Klais CM, et al. A novel TIMP3 mutation associated with Sorsby fundus dystrophy[J]. Arch Ophthalmol, 2005, 123(4): 542-543. DOI: 10.1001/archopht.123.4.542.
20. Baston A, Gerhardt C, Zandi S, et al. Visual outcome after Intravitreal anti-VEGF therapy for macular neovascularisation secondary to Sorsby's fundus dystrophy: a systematic review[J/OL]. J Clin Med, 2021, 10(11): 2433[2021-05-30]. https://pubmed.ncbi.nlm.nih.gov/34070857/. DOI: 10.3390/jcm10112433.
21. Gemenetzi MK, Luff AJ, Lotery AJ. Successful treatment of choroidal neovascularization secondary to Sorsby fundus dystrophy with intravitreal Bevacizumab[J]. Retin Cases Brief Rep, 2011, 5(2): 132-135. DOI: 10.1097/ICB.0b013e3181cc216b.
22. Gray TL, Wong HC, Raymond GL. Choroidal neovascularization secondary to Sorsby fundus dystrophy treated with intravitreal Bevacizumab[J]. Retin Cases Brief Rep, 2012, 6(2): 193-196. DOI: 10.1097/ICB.0b013e31822476fd.
23. Balaskas K, Hovan M, Mahmood S, et al. Ranibizumab for the management of Sorsby fundus dystrophy[J]. Eye, 2013, 27(1): 101-102. DOI: 10.1038/eye.2012.221.
24. Copete-Piqueras S, Cava-Valenciano C, Flores-Moreno I, et al. Tratamiento antiangiogénico en fondo de distrofia de Sorsby sin mutación en gen de TIMP-3[J]. Arch Soc Españ ola Oftalmol, 2013, 88(6): 240-243. DOI: 10.1016/j.oftal.2011.12.005.
25. Kapoor KG, Bakri SJ. Intravitreal anti-vascular endothelial growth factor therapy for choroidal neovascularization due to Sorsby macular dystrophy[J]. J Ocul Pharmacol Ther, 2013, 29(4): 444-447. DOI: 10.1089/jop.2011.0206.
26. Keller J, Giralt J, Alforja S, et al. Altering the clinical course of Sorsby fundus dystrophy with the use of anti-vascular endothelial growth factor intraocular therapy[J]. Retin Cases Brief Rep, 2015, 9(2): 104-105. DOI: 10.1097/ICB.0000000000000103.
27. Mohla A, Khan K, Kasilian M, et al. OCT angiography in the management of choroidal neovascular membrane secondary to Sorsby fundus dystrophy[J/OL]. BMJ Case Rep, 2016, 2016: bcr2016216453[2016-09-01]. https://casereports.bmj.com/content/2016/bcr-2016-216453.long. DOI: 10.1136/bcr-2016-216453.
28. Menassa N, Burgula S, Empeslidis T, et al. Bilateral choroidal neovascular membrane in a young patient with Sorsby fundus dystrophy: the value of prompt treatment[J/OL]. BMJ Case Rep, 2017, 2017: bcr2017220488[2017-08-03]. https://pubmed.ncbi.nlm.nih.gov/28775088/. DOI: 10.1136/bcr-2017-220488.
29. Tsokolas G, Almuhtaseb H, Lotery A. Evaluation of Pro-re-Nata (PRN) and treat and extend Bevacizumab treatment protocols in Sorsby fundus dystrophy[J]. Eur J Ophthalmol, 2018, 30(1): 26-33.
30. Kaye R, Lotery A. Long-term outcome of Bevacizumab therapy in Sorsby fundus dystrophy, a case series[J]. Investig Ophthalmol Vis Sci, 2017, 58: 229.
31. Sanz GF, Alonso-Gonzalez R, Keane P, et al. Treatment with intravitreal an-ti-VEGF for choroidal neovascular membrane secondary to Sorsby's fundus dystrophy: a 24-month analysis[J/OL]. Invest Ophthal Vis Sci, 2013, 54: 3863[2013-06-01]. https://iovs.arvojournals.org/article.aspx?articleid=2148681.
32. Hoskin A, Sehmi K, Bird AC. Sorsby's pseudoinflammatory macular dystrophy[J]. Brit J Ophthal, 1981, 65(12): 859-865. DOI: 10.1136/bjo.65.12.859.
33. Klenotic PA, Munier FL, Marmorstein LY, et al. Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of epithelial growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1). Implications for macular degenerations[J]. J Biol Chem, 2004, 279(29): 30469-30473. DOI: 10.1074/jbc.M403026200.

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Sorsby's fundus dystrophy: a systematic review

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