Structural and microvascular retinal changes in keratoconus: an OCT and OCT angiography study
Medical hypothesis, discovery & innovation in optometry,
Vol. 6 No. 3 (2025),
21 November 2025
,
Page 104-111
https://doi.org/10.51329/mehdioptometry229
Abstract
Background: Keratoconus is increasingly recognized as a condition that may affect not only corneal structure but also posterior segment parameters. This study aimed to evaluate alterations in central macular, choroidal, and peripapillary retinal nerve fiber layer thicknesses, as well as peripapillary vessel densities (VDs), in eyes with keratoconus using optical coherence tomography (OCT) and OCT angiography (OCTA).Methods: This cross-sectional study included eyes with keratoconus and healthy control eyes. Participants underwent Scheimpflug corneal tomography (Pentacam HR) to assess central corneal thickness (CCT) and keratometry; spectral-domain OCT (SD-OCT) for central macular thickness (CMT), choroidal thickness, and peripapillary retinal nerve fiber layer thickness (RNFLT) measurements; and swept-source OCT angiography (SS-OCTA) to quantify peripapillary VD centrally and across four quadrants at the superficial and deep capillary plexuses (pSCP, pDCP), the peripapillary choriocapillaris (pCC), and the global radial peripapillary capillary plexus (nRPCP).
Results: Eighty-six eyes with keratoconus and 86 age-, sex-, axial-length-, and laterality-matched healthy controls (all P > 0.05) were analyzed. The keratoconus group showed significantly higher spherical equivalent, higher keratometry parameters, higher astigmatism, and lower CCT, along with worse best-corrected distance visual acuity (all P < 0.001). Mean choroidal thickness was significantly greater in eyes with keratoconus (P < 0.001), whereas CMT, global RNFLT, and most quadrant RNFLT measures were comparable (all P > 0.05), except for a thinner inferonasal RNFLT (P < 0.05). Central VD in the pSCP, pDCP, pCC, and global nRPCP were significantly reduced (all P < 0.05). Eyes with keratoconus additionally demonstrated a non-significant (all P > 0.05) but characteristic pattern of regional VD alterations across peripapillary sectors.
Conclusions: Keratoconus was associated with significant microvascular and structural alterations extending beyond the cornea, including reduced VDs in central peripapillary plexuses, localized thinning of inferonasal RNFL, and increased choroidal thickness. These findings support a broader pathophysiologic framework in which keratoconus involves not only anterior corneal remodeling but also measurable changes in blood supply within the macular and lamina cribrosa regions. The characteristic, though nonsignificant, regional VD patterns further underscore potential sectoral vulnerability. Future longitudinal and multimodal imaging studies are warranted to clarify the temporal evolution, clinical relevance, and prognostic utility of these microvascular changes in keratoconus.
Keywords:
- choriocapillaris
- choroids
- retina
- macula luteas
- optical coherence tomography
- optical coherence tomography angiography
- optic nerves
- peripapillary retinal nerve fiber layer
- retinal nerve fiber layer
- keratoconus
References
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9. Wyl?ga?a A, Szkodny D, Fiolka R, Wyl?ga?a E. Assessment of the Retinal Vessels in Keratoconus: An OCT Angiography Study. J Clin Med. 2022 May 24;11(11):2960. doi: 10.3390/jcm11112960. PMID: 35683349; PMCID: PMC9181444.
10. Akkaya S. Macular and Peripapillary Choroidal Thickness in Patients With Keratoconus. Ophthalmic Surg Lasers Imaging Retina. 2018 Sep 1;49(9):664-673. doi: 10.3928/23258160-20180831-03. PMID: 30222800.
11. Bilgin B, Karadag AS. Choroidal thickness in keratoconus. Int Ophthalmol. 2020 Jan;40(1):135-140. doi: 10.1007/s10792-019-01156-y. Epub 2019 Aug 20. PMID: 31432355.
12. Gutierrez-Bonet R, Ruiz-Medrano J, Peña-Garcia P, Catanese M, Sadeghi Y, Hashemi K, Gabison E, Ruiz-Moreno JM. Macular Choroidal Thickening in Keratoconus Patients: Swept-Source Optical Coherence Tomography Study. Transl Vis Sci Technol. 2018 Jun 7;7(3):15. doi: 10.1167/tvst.7.3.15. PMID: 29888113; PMCID: PMC5991807.
13. Pinheiro-Costa J, Viana Pinto J, Perestrelo S, Beato JN, Torrão L, Brandão E, Carneiro Â, Madeira MD, Falcão-Reis F. Increased Choroidal Thickness in Keratoconus Patients: Perspectives in the Disease Pathophysiology. J Ophthalmol. 2019 Dec 3;2019:2453931. doi: 10.1155/2019/2453931. PMID: 31871781; PMCID: PMC6913161.
14. Pinheiro-Costa J, Correia PJ, Pinto JV, Alves H, Torrão L, Moreira R, Falcão M, Carneiro Â, Madeira MD, Falcão-Reis F. Increased choroidal thickness is not a disease progression marker in keratoconus. Sci Rep. 2020 Nov 17;10(1):19938. doi: 10.1038/s41598-020-77122-x. PMID: 33203915; PMCID: PMC7673983.
15. Gutierrez-Bonet R, Ruiz-Medrano J, Biarnés M, Rasheed MA, Vupparaboina KK, Chhablani J, Ruiz-Moreno JM. Analysis of Choroidal Vascularity Index in Keratoconus Patients Using Swept-Source Optical Coherence Tomography-Based Binarization Techniques. J Ophthalmol. 2020 Jan 8;2020:1682463. doi: 10.1155/2020/1682463. PMID: 32025344; PMCID: PMC6984744.
16. Akkaya S, Küçük B. Lamina Cribrosa Thickness in Patients With Keratoconus. Cornea. 2017 Dec;36(12):1509-1513. doi: 10.1097/ICO.0000000000001379. PMID: 28922330.
17. Dogan B, Bozdogan YC, Gedik B, Erol MK, Bulut M, Duman F. Optic disc and retinal vessel densities assessment by optical coherence tomography angiography in patients with keratoconus. Photodiagnosis Photodyn Ther. 2023 Mar;41:103218. doi: 10.1016/j.pdpdt.2022.103218. Epub 2022 Nov 30. PMID: 36462703.
18. Vahedi H, Abdollahi M, Moshfeghinia R, Emami S, Sobhi N, Sorkhabi R, Jafarizadeh A. Retinal thickness and vascular density changes in Keratoconus: A systematic review and meta-analysis. Heliyon. 2025 Jan 18;11(2):e42099. doi: 10.1016/j.heliyon.2025.e42099. PMID: 39925350; PMCID: PMC11804566.
19. Gomes JA, Tan D, Rapuano CJ, Belin MW, Ambrósio R Jr, Guell JL, Malecaze F, Nishida K, Sangwan VS; Group of Panelists for the Global Delphi Panel of Keratoconus and Ectatic Diseases. Global consensus on keratoconus and ectatic diseases. Cornea. 2015 Apr;34(4):359-69. doi: 10.1097/ICO.0000000000000408. PMID: 25738235.
20. Bayat K, Pooyan P, Feizi S, Ahmadieh H, Hafezi F, Pourhoseingholi MA, Fekri S, Sarraf D. Structural alterations in the retina and choroid of keratoconus patients detected by optical coherence tomography: A systematic review and meta-analysis. Surv Ophthalmol. 2025 Nov 4:S0039-6257(25)00195-X. doi: 10.1016/j.survophthal.2025.11.004. Epub ahead of print. PMID: 41197878.
21. Y?ld?z MB, Bolaç R. Is Keratoconus More Than Just a Corneal Disease? Cornea. 2024 Mar 1;43(3):360-364. doi: 10.1097/ICO.0000000000003366. Epub 2023 Aug 22. PMID: 37607306.
2. Kalkan Akcay E, Akcay M, Uysal BS, Kosekahya P, Aslan AN, Caglayan M, Koseoglu C, Yulek F, Cagil N. Impaired corneal biomechanical properties and the prevalence of keratoconus in mitral valve prolapse. J Ophthalmol. 2014;2014:402193. doi: 10.1155/2014/402193. Epub 2014 Apr 17. PMID: 24864193; PMCID: PMC4016888.
3. Ponsioen TL, van Luyn MJ, van der Worp RJ, van Meurs JC, Hooymans JM, Los LI. Collagen distribution in the human vitreoretinal interface. Invest Ophthalmol Vis Sci. 2008 Sep;49(9):4089-95. doi: 10.1167/iovs.07-1456. Epub 2008 Apr 30. PMID: 18450587.
4. McBrien NA, Gentle A. Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res. 2003 May;22(3):307-38. doi: 10.1016/s1350-9462(02)00063-0. PMID: 12852489.
5. Chaerkady R, Shao H, Scott SG, Pandey A, Jun AS, Chakravarti S. The keratoconus corneal proteome: loss of epithelial integrity and stromal degeneration. J Proteomics. 2013 Jul 11;87:122-31. doi: 10.1016/j.jprot.2013.05.023. Epub 2013 May 29. PMID: 23727491; PMCID: PMC3721369.
6. Ihanamäki T, Pelliniemi LJ, Vuorio E. Collagens and collagen-related matrix components in the human and mouse eye. Prog Retin Eye Res. 2004 Jul;23(4):403-34. doi: 10.1016/j.preteyeres.2004.04.002. PMID: 15219875.
7. Hashemi H, Heirani M, Ambrósio R Jr, Hafezi F, Naroo SA, Khorrami-Nejad M. The link between Keratoconus and posterior segment parameters: An updated, comprehensive review. Ocul Surf. 2022 Jan;23:116-122. doi: 10.1016/j.jtos.2021.12.004. Epub 2021 Dec 8. PMID: 34890805.
8. Pierro L, Bianco L, Bertuzzi F, Arrigo A, Saladino A, Distefano A, Berni A, Knutsson KA, Rama P, Bandello F. New Findings in Early-Stage Keratoconus: Lamina Cribrosa Curvature, Retinal Nerve Fiber Layer Thickness, and Vascular Perfusion. Am J Ophthalmol. 2023 Feb;246:122-129. doi: 10.1016/j.ajo.2022.10.012. Epub 2022 Oct 30. PMID: 36323392.
9. Wyl?ga?a A, Szkodny D, Fiolka R, Wyl?ga?a E. Assessment of the Retinal Vessels in Keratoconus: An OCT Angiography Study. J Clin Med. 2022 May 24;11(11):2960. doi: 10.3390/jcm11112960. PMID: 35683349; PMCID: PMC9181444.
10. Akkaya S. Macular and Peripapillary Choroidal Thickness in Patients With Keratoconus. Ophthalmic Surg Lasers Imaging Retina. 2018 Sep 1;49(9):664-673. doi: 10.3928/23258160-20180831-03. PMID: 30222800.
11. Bilgin B, Karadag AS. Choroidal thickness in keratoconus. Int Ophthalmol. 2020 Jan;40(1):135-140. doi: 10.1007/s10792-019-01156-y. Epub 2019 Aug 20. PMID: 31432355.
12. Gutierrez-Bonet R, Ruiz-Medrano J, Peña-Garcia P, Catanese M, Sadeghi Y, Hashemi K, Gabison E, Ruiz-Moreno JM. Macular Choroidal Thickening in Keratoconus Patients: Swept-Source Optical Coherence Tomography Study. Transl Vis Sci Technol. 2018 Jun 7;7(3):15. doi: 10.1167/tvst.7.3.15. PMID: 29888113; PMCID: PMC5991807.
13. Pinheiro-Costa J, Viana Pinto J, Perestrelo S, Beato JN, Torrão L, Brandão E, Carneiro Â, Madeira MD, Falcão-Reis F. Increased Choroidal Thickness in Keratoconus Patients: Perspectives in the Disease Pathophysiology. J Ophthalmol. 2019 Dec 3;2019:2453931. doi: 10.1155/2019/2453931. PMID: 31871781; PMCID: PMC6913161.
14. Pinheiro-Costa J, Correia PJ, Pinto JV, Alves H, Torrão L, Moreira R, Falcão M, Carneiro Â, Madeira MD, Falcão-Reis F. Increased choroidal thickness is not a disease progression marker in keratoconus. Sci Rep. 2020 Nov 17;10(1):19938. doi: 10.1038/s41598-020-77122-x. PMID: 33203915; PMCID: PMC7673983.
15. Gutierrez-Bonet R, Ruiz-Medrano J, Biarnés M, Rasheed MA, Vupparaboina KK, Chhablani J, Ruiz-Moreno JM. Analysis of Choroidal Vascularity Index in Keratoconus Patients Using Swept-Source Optical Coherence Tomography-Based Binarization Techniques. J Ophthalmol. 2020 Jan 8;2020:1682463. doi: 10.1155/2020/1682463. PMID: 32025344; PMCID: PMC6984744.
16. Akkaya S, Küçük B. Lamina Cribrosa Thickness in Patients With Keratoconus. Cornea. 2017 Dec;36(12):1509-1513. doi: 10.1097/ICO.0000000000001379. PMID: 28922330.
17. Dogan B, Bozdogan YC, Gedik B, Erol MK, Bulut M, Duman F. Optic disc and retinal vessel densities assessment by optical coherence tomography angiography in patients with keratoconus. Photodiagnosis Photodyn Ther. 2023 Mar;41:103218. doi: 10.1016/j.pdpdt.2022.103218. Epub 2022 Nov 30. PMID: 36462703.
18. Vahedi H, Abdollahi M, Moshfeghinia R, Emami S, Sobhi N, Sorkhabi R, Jafarizadeh A. Retinal thickness and vascular density changes in Keratoconus: A systematic review and meta-analysis. Heliyon. 2025 Jan 18;11(2):e42099. doi: 10.1016/j.heliyon.2025.e42099. PMID: 39925350; PMCID: PMC11804566.
19. Gomes JA, Tan D, Rapuano CJ, Belin MW, Ambrósio R Jr, Guell JL, Malecaze F, Nishida K, Sangwan VS; Group of Panelists for the Global Delphi Panel of Keratoconus and Ectatic Diseases. Global consensus on keratoconus and ectatic diseases. Cornea. 2015 Apr;34(4):359-69. doi: 10.1097/ICO.0000000000000408. PMID: 25738235.
20. Bayat K, Pooyan P, Feizi S, Ahmadieh H, Hafezi F, Pourhoseingholi MA, Fekri S, Sarraf D. Structural alterations in the retina and choroid of keratoconus patients detected by optical coherence tomography: A systematic review and meta-analysis. Surv Ophthalmol. 2025 Nov 4:S0039-6257(25)00195-X. doi: 10.1016/j.survophthal.2025.11.004. Epub ahead of print. PMID: 41197878.
21. Y?ld?z MB, Bolaç R. Is Keratoconus More Than Just a Corneal Disease? Cornea. 2024 Mar 1;43(3):360-364. doi: 10.1097/ICO.0000000000003366. Epub 2023 Aug 22. PMID: 37607306.
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