Skip to main content

Advertisement

SpringerLink
Log in

Anterior segment phenotypic changes in late-onset retinal degeneration with Ser163Arg mutation in CTRP5/C1QTNF5

  • Retinal Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Late-onset retinal degeneration (L-ORD) is a rare retinal dystrophy with anterior segment (AS) abnormalities, including long anterior zonules (LAZ) and iris atrophy. This investigation evaluates AS changes in a L-ORD cohort.

Methods

Prospective, longitudinal study including L-ORD individuals (Ser163Arg) with ocular exam and standard slit-lamp photographs between 2011 and 2022. AS images were merged and assessed for LAZ number and zonule-free zone (ZFZ) radius. Further clinical findings such as iris atrophy patterns were reported descriptively.

Results

Twelve eyes of 6 patients (4 males, median age = 60.5 years) were included, showing a median of 160 (11–372) LAZs, mainly localized superiorly (39%) and inferiorly (24%). There was a high inter-ocular correlation (rs = 0.94, p < 0.01), no difference in LAZ count between eyes (p = 0.82), and an inverse relationship between LAZ and age (r =  − 0.82; p < 0.05). The ZFZ had median 2.1 mm (1.3–5.4), with no inter-ocular difference (p = 0.31). Iris transillumination defects occurred in 11/12 eyes, with 4 major patterns identified: pupillary ruff rarefaction (10/12), patchy atrophy (6/12), notched defects (6/12), and radial streaks (2/12). In a short-term follow-up of 5.9 years, 4 eyes showed a reduction in LAZ count to median 139.5 (67–169) (p = 0.50) and a concomitant increase in ZFZ measurement to median 2.2 (1.7–2.6) (p = 0.17).

Conclusion

This study confirms symmetric LAZs count and ZFZ in L-ORD, with ZFZ measurements smaller than in previous cohorts. A reduction in LAZs count and an increase in ZFZ with age were suggested longitudinally, yet findings need further evaluation as follow-up was limited to two cases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

AL:

Axial length

AMD:

Age-related macular degeneration

AS:

Anterior segment

hPD:

Horizontal pupil diameter

LAZ:

Long anterior zonules

L-ORD:

Late-onset retinal degeneration

RPE:

Retinal pigment epithelium

SE:

Spherical equivalent

ZFZ:

Zonule-free zone

References

  1. Hayward C, Shu X, Cideciyan AV, Lennon A, Barran P, Zareparsi S, Sawyer L, Hendry G, Dhillon B, Milam AH, Luthert PJ, Swaroop A, Hastie ND, Jacobson SG, Wright AF (2003) Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration. Hum Mol Genet 12:2657–2667. https://doi.org/10.1093/hmg/ddg289

    Article  CAS  PubMed  Google Scholar 

  2. Ayyagari R, Mandal MNA, Karoukis AJ, Chen L, McLaren NC, Lichter M, Wong DT, Hitchcock PF, Caruso RC, Moroi SE, Maumenee IH, Sieving PA (2005) Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation. Invest Ophthalmol Vis Sci 46:3363–3371. https://doi.org/10.1167/iovs.05-0159

    Article  PubMed  Google Scholar 

  3. Mandal MN, Vasireddy V, Reddy GB, Wang X, Moroi SE, Pattnaik BR, Hughes BA, Heckenlively JR, Hitchcock PF, Jablonski MM, Ayyagari R (2006) CTRP5 is a membrane-associated and secretory protein in the RPE and ciliary body and the S163R mutation of CTRP5 impairs its secretion. Invest Ophthalmol Vis Sci 47:5505–5513. https://doi.org/10.1167/iovs.06-0312

    Article  PubMed  Google Scholar 

  4. Lando L, Borooah S (2022) Late-onset retinal degeneration: clinical perspectives. Clin Ophthalmol 16:3225–3246. https://doi.org/10.2147/opth.S362691

    Article  PubMed  PubMed Central  Google Scholar 

  5. Milam AH, Curcio CA, Cideciyan AV, Saxena S, John SK, Kruth HS, Malek G, Heckenlively JR, Weleber RG, Jacobson SG (2000) Dominant late-onset retinal degeneration with regional variation of sub-retinal pigment epithelium deposits, retinal function, and photoreceptor degeneration. Ophthalmology 107:2256–2266. https://doi.org/10.1016/s0161-6420(00)00419-x

    Article  CAS  PubMed  Google Scholar 

  6. Jacobson SG, Cideciyan AV, Wright E, Wright AF (2001) Phenotypic marker for early disease detection in dominant late-onset retinal degeneration. Invest Ophthalmol Vis Sci 42:1882–1890

    CAS  PubMed  Google Scholar 

  7. Subrayan V, Morris B, Armbrecht AM, Wright AF, Dhillon B (2005) Long anterior lens zonules in late-onset retinal degeneration (L-ORD). Am J Ophthalmol 140:1127–1129. https://doi.org/10.1016/j.ajo.2005.06.023

    Article  PubMed  Google Scholar 

  8. Vincent A, Munier FL, Vandenhoven CC, Wright T, Westall CA, Héon E (2012) The characterization of retinal phenotype in a family with C1QTNF5-related late-onset retinal degeneration. Retina 32:1643–1651. https://doi.org/10.1097/IAE.0b013e318240a574

    Article  PubMed  Google Scholar 

  9. Soumplis V, Sergouniotis PI, Robson AG, Michaelides M, Moore AT, Holder GE, Webster AR (2013) Phenotypic findings in C1QTNF5 retinopathy (late-onset retinal degeneration). Acta Ophthalmol 91:e191-195. https://doi.org/10.1111/aos.12010

    Article  CAS  PubMed  Google Scholar 

  10. Jacobson SG, Cideciyan AV, Sumaroka A, Roman AJ, Wright AF (2014) Late-onset retinal degeneration caused by C1QTNF5 mutation: sub-retinal pigment epithelium deposits and visual consequences. JAMA Ophthalmol 132:1252–1255. https://doi.org/10.1001/jamaophthalmol.2014.2059

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cukras C, Flamendorf J, Wong WT, Ayyagari R, Cunningham D, Sieving PA (2016) Longitudinal structural changes in late-onset retinal degeneration. Retina 36:2348–2356. https://doi.org/10.1097/iae.0000000000001113

    Article  PubMed  PubMed Central  Google Scholar 

  12. Papastavrou VT, O’Brien JM, Regan AJ, Aftab AM, Browning AC (2020) The progression of macular structural and functional changes in late-onset retinal degeneration. Retin Cases Brief Rep. https://doi.org/10.1097/icb.0000000000001067

    Article  Google Scholar 

  13. Borooah S, Papastavrou V, Lando L, Han J, Lin JH, Ayyagari R, Dhillon B, Browning AC (2021) Reticular pseudodrusen in late-onset retinal degeneration. Ophthalmol Retina 5:1043–1051. https://doi.org/10.1016/j.oret.2020.12.012

    Article  PubMed  Google Scholar 

  14. Borooah S, Papastavrou VT, Lando L, Moghimi S, Lin T, Dans K, Motevasseli T, Cameron JR, Freeman WR, Dhillon B, Browning AC (2021) Characterizing the natural history of foveal-sparing atrophic late-onset retinal degeneration. Retina 41:1329–1337. https://doi.org/10.1097/iae.0000000000003017

    Article  CAS  PubMed  Google Scholar 

  15. De Zaeytijd J, Coppieters F, De Bruyne M, Van Royen J, Roels D, Six R, Van Cauwenbergh C, De Baere E, Leroy BP (2021) Longitudinal phenotypic study of late-onset retinal degeneration due to a founder variant c.562C>A p. (Pro188Thr) in the C1QTNF5 gene. Ophthalmic Genet 42:521–532. https://doi.org/10.1080/13816810.2021.1923041

    Article  CAS  PubMed  Google Scholar 

  16. Vanderford EK, De Silva T, Noriega D, Arango M, Cunningham D, Cukras CA (2021) Quantitative analysis of longitudinal changes in multimodal imaging of late-onset retinal degeneration. Retina 41:1701–1708. https://doi.org/10.1097/iae.0000000000003082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ayyagari R, Griesinger IB, Bingham E, Lark KK, Moroi SE, Sieving PA (2000) Autosomal dominant hemorrhagic macular dystrophy not associated with the TIMP3 gene. Arch Ophthalmol 118:85–92. https://doi.org/10.1001/archopht.118.1.85

    Article  CAS  PubMed  Google Scholar 

  18. Papastavrou VT, Borooah S, O’Brien JM, Ray-Chaudhuri N, Dhillon B, Vieira RV, Browning AC (2017) Cataract surgery in patients with late-onset retinal degeneration. J Cataract Refract Surg 43:1036–1043. https://doi.org/10.1016/j.jcrs.2017.05.041

    Article  PubMed  Google Scholar 

  19. Borooah S, Collins C, Wright A, Dhillon B (2009) Late-onset retinal macular degeneration: clinical insights into an inherited retinal degeneration. Br J Ophthalmol 93:284–289. https://doi.org/10.1136/bjo.2008.150151

    Article  CAS  PubMed  Google Scholar 

  20. Lando L, Nguyen AX-L, Li R, Megaw R, Dhillon B, Borooah S (2022) Quantification of long anterior zonules in late-onset retinal degeneration. Invest Ophthalmol Vis Sci 63:4408 – F0087–4408 – F0087

  21. Roberts DK, Wilensky J (2012) Long anterior lens zonules. Clin Exp Ophthalmol 40:764–766. https://doi.org/10.1111/j.1442-9071.2012.02787.x

    Article  PubMed  Google Scholar 

  22. Roberts DK, Yang Y, Morettin CE, Doan T, Newman TL, Wilensky JT (2015) Quantification of long anterior lens zonules and their resulting zonule-free zone sizes. Clin Exp Ophthalmol 43:773–775. https://doi.org/10.1111/ceo.12554

    Article  PubMed  PubMed Central  Google Scholar 

  23. Roberts DK, Yang Y, Morettin CE, Newman TL, Roberts MF, Wilensky JT (2017) Morphologic patterns formed by the anomalous fibers occurring along the anterior capsule of the crystalline lens in people with the long anterior zonule trait. Anat Rec (Hoboken) 300:1336–1347. https://doi.org/10.1002/ar.23570

    Article  PubMed  Google Scholar 

  24. Christen R, Pache M, Teuchner B, Meyer P, Prünte C, Flammer J (2003) Iris transillumination defects in patients with primary open angle glaucoma. Eur J Ophthalmol 13:365–369. https://doi.org/10.1177/112067210301300406

    Article  CAS  PubMed  Google Scholar 

  25. Fingert JH, Burden JH, Wang K, Kwon YH, Alward WL, Anderson MG (2013) Circumferential iris transillumination defects in exfoliation syndrome. J Glaucoma 22:555–558. https://doi.org/10.1097/IJG.0b013e318255da16

    Article  PubMed  PubMed Central  Google Scholar 

  26. Armstrong RA (2013) Statistical guidelines for the analysis of data obtained from one or both eyes. Ophthalmic Physiol Opt 33:7–14. https://doi.org/10.1111/opo.12009

    Article  PubMed  Google Scholar 

  27. Karakosta A, Vassilaki M, Plainis S, Elfadl NH, Tsilimbaris M, Moschandreas J (2012) Choice of analytic approach for eye-specific outcomes: one eye or two? Am J Ophthalmol 153:571-579.e571. https://doi.org/10.1016/j.ajo.2011.08.032

    Article  PubMed  Google Scholar 

  28. Mackey DA, Wilkinson CH, Kearns LS, Hewitt AW (2011) Classification of iris colour: review and refinement of a classification schema. Clin Experiment Ophthalmol 39:462–471. https://doi.org/10.1111/j.1442-9071.2010.02487.x

    Article  PubMed  Google Scholar 

  29. Bassnett S (2021) Zinn’s zonule. Prog Retin Eye Res 82:100902. https://doi.org/10.1016/j.preteyeres.2020.100902

  30. Roberts DK, Wilensky JT (2012) Persistent pupillary membranes and long anterior zonules. Invest Ophthalmol Vis Sci 53:5059–5059

    Google Scholar 

  31. Roberts DK, Newman TL, Roberts MF, Wilensky JT (2014) Remnants of the anterior tunica vasculosa lentis and long anterior lens zonules. J Glaucoma 23:441–445. https://doi.org/10.1097/IJG.0b013e3182946522

    Article  PubMed  PubMed Central  Google Scholar 

  32. Rieger G (1981) Radial retroiridal linear pigmentation. Br J Ophthalmol 65:760–761. https://doi.org/10.1136/bjo.65.11.760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Roberts DK, Ayyagari R, McCarthy B, Xie H, Davis F, Wilensky JT (2013) Investigating ocular dimensions in African Americans with long anterior zonules. J Glaucoma 22:393–397. https://doi.org/10.1097/IJG.0b013e3182447d6c

    Article  PubMed  PubMed Central  Google Scholar 

  34. Sturrock GD, Tripathi RC (1976) Pigmented lens striae. Br J Ophthalmol 60:287–293. https://doi.org/10.1136/bjo.60.4.287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Roberts DK, Ayyagari R, Moroi SE (2008) Possible association between long anterior lens zonules and plateau iris configuration. J Glaucoma 17:393–396. https://doi.org/10.1097/IJG.0b013e31815c3b04

    Article  PubMed  Google Scholar 

  36. Roberts DK, Newman TL, Roberts MF, Teitelbaum BA, Winters JE (2018) Long anterior lens zonules and intraocular pressure. Invest Ophthalmol Vis Sci 59:2015–2023. https://doi.org/10.1167/iovs.17-23705

    Article  PubMed  PubMed Central  Google Scholar 

  37. Roberts DK, Yang Y, Wilensky JT (2014) Cataract surgery in African Americans with long anterior lens zonules. Clin Exp Ophthalmol 42:898–900. https://doi.org/10.1111/ceo.12341

    Article  PubMed  Google Scholar 

  38. Moroi SE, Lark KK, Sieving PA, Nouri-Mahdavi K, Schlötzer-Schrehardt U, Katz GJ, Ritch R (2003) Long anterior zonules and pigment dispersion. Am J Ophthalmol 136:1176–1178. https://doi.org/10.1016/s0002-9394(03)00657-3

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the photography department at the Princess Alexandra Eye Pavilion, Edinburgh, UK.

Funding

Leonardo Lando is supported by the Sear Scholarship, Pan-American Association of Ophthalmology (PAAO), awarded in 2019. Randa Tsz Ha Li is supported by the LifeArc Philanthropic Fund towards a therapy for late-onset retinal degeneration (L-ORD), awarded in June 2020. Roly Megaw is supported by the Wellcome Trust (grant n. 219607/Z/19/Z). Shyamanga Borooah is supported in part by the University of California San Diego Vision Research Center Core Grant P30EY022589 and an unrestricted grant from Research to Prevent Blindness, NY, Foundation fighting Blindness Career development award and the Nixon Visions foundation. The funding organizations had no role in the design or conduct of this research.

Author information

Authors and Affiliations

  1. Shiley Eye Institute, University of California San Diego, La Jolla, CA, 92093, USA

    Leonardo Lando & Shyamanga Borooah

  2. Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada

    Leonardo Lando

  3. Faculty of Medicine, McGill University, Montreal, Canada

    Anne Xuan-Lan Nguyen

  4. Centre for Clinical Brain Sciences, School of Clinical Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, Scotland, UK

    Randa Tsz Ha Li & Baljean Dhillon

  5. Princess Alexandra Eye Pavilion, NHS Lothian, Edinburgh, Scotland, UK

    Randa Tsz Ha Li, Roly Megaw & Baljean Dhillon

  6. MRC Human Genetics Unit, University of Edinburgh, Edinburgh, Scotland, UK

    Roly Megaw

Authors
  1. Leonardo Lando
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Xuan-Lan Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Randa Tsz Ha Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roly Megaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Baljean Dhillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shyamanga Borooah
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LL: research design; data acquisition; research execution; data analysis; results interpretation; manuscript writing; manuscript review. AXLN: research design; data acquisition; data analysis; manuscript review. RTHL: data acquisition; research execution; manuscript review. RM: research design; data analysis; results interpretation; manuscript review. BD: research design; data analysis; results interpretation; manuscript review. SB: research design; data acquisition; research execution; data analysis; results interpretation; manuscript writing; manuscript review.

Corresponding author

Correspondence to Shyamanga Borooah.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the research committee at Newcastle University (11/NE/0199) and abided by the tenets of the Declaration of Helsinki and the National Health Service Trust hospitals. Full informed consent was obtained from all participants enrolled in this prospective cohort.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lando, L., Nguyen, A.XL., Li, R.T.H. et al. Anterior segment phenotypic changes in late-onset retinal degeneration with Ser163Arg mutation in CTRP5/C1QTNF5. Graefes Arch Clin Exp Ophthalmol 261, 2507–2516 (2023). https://doi.org/10.1007/s00417-023-06041-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-023-06041-0

Keywords

Search

Navigation