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Choroidal and retinal alteration after long-term use of tadalafil: a prospective non-randomized clinical trial

  • Luca D’Andrea , Gianluigi Califano , Marco Abate EMAIL logo , Marco Capece , Claudia Collà Ruvolo , Felice Crocetto , Maria Laura Passaro , Gilda Cennamo and Ciro Costagliola
Published/Copyright: November 13, 2024

Abstract

Objectives

The purpose of this study is to investigate choroidal and retinal vascular features in patients taking PDE5is by measuring dynamic vascular alterations and neurostructural features of the retina before and after oral tadalafil administration.

Methods

The current clinical research involved 22 patients treated with tadalafil 20 mg on alternate days (OAD) after nerve-sparing robotic radical prostatectomy (NS-RARP) for prostate cancer. Patients underwent SD-OCT to assess ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), and subfoveal choroidal thickness (SFCT), as well as OCTA to assess superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), foveal avascular zone (FAZ), and radial peripapillary capillary thickness (RPC). All patients were evaluated at baseline (t0), and 3 (t1) and 6 (t2) months after the use of oral tadalafil.

Results

A statistically significant reduction in DCP and CC vessel density was found at t2 compared to baseline. According to the SFCT parameter, a statistically significant increase was observed from t0 to t1, and from t1 to t2. GCC parameter increased at t2 compared to baseline in a statistically significant way. No statistically significant differences were recorded between t0, t1 and t2 for the SCP, RPC, FAZ area, RNFL parameter.

Conclusions

Retinal and optic disc toxicity may be detected using modifications of capillary vessel density. Further studies are needed to detect the possible progression or regression of ocular or systemic vascular complications in long-term follow-up.


Corresponding author: Marco Abate, Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples “Federico II”, Via Sergio Pansini n°5, 80138, Naples, Italy, E-mail:

  1. Research ethics: The local Institutional Review Board deemed the study exempt from review.

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interests: Authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Not applicable.

References

1. Cappelleri, JC, Tseng, LJ, Stecher, V, Goldstein, I. Enriching the interpretation of the erectile dysfunction inventory of treatment satisfaction: characterizing success in treatment satisfaction. J Sex Med 2018;15:732–40. https://doi.org/10.1016/j.jsxm.2018.03.078.Search in Google Scholar PubMed

2. Vlachopoulos, C, Ioakeimidis, N, Aznaouridis, K, Terentes-Printzios, D, Rokkas, K, Aggelis, A, et al.. Prediction of cardiovascular events with aortic stiffness in patients with erectile dysfunction. Hypertension 2014;64:672–8. https://doi.org/10.1161/HYPERTENSIONAHA.114.03369.Search in Google Scholar PubMed

3. Moschos, MM, Nitoda, E. Pathophysiology of visual disorders induced by phosphodiesterase inhibitors in the treatment of erectile dysfunction. Drug Des Dev Ther 2016;8:3407–13. https://doi.org/10.2147/DDDT.S118015.Search in Google Scholar PubMed PubMed Central

4. Diederen, RM, La Heij, EC, Markerink-van Ittersum, M, Kijlstra, A, Hendrikse, F, de Vente, J. Selective blockade of phosphodiesterase types 2, 5 and 9 results in cyclic 3’5’ guanosine monophosphate accumulation in retinal pigment epithelium cells. Br J Ophthalmol 2007;91:379–84. https://doi.org/10.1136/bjo.2006.100628.Search in Google Scholar PubMed PubMed Central

5. Marmor, MF, Kessler, R. Sildenafil (viagra) and ophthalmology. Surv Ophthalmol 1999;44:153–62. https://doi.org/10.1016/s0039-6257(99)00079-x.Search in Google Scholar PubMed

6. Gedik, S, Yilmaz, G, Akova, YA. Sildenafil-associated consecutive nonarteritic anterior ischaemic optic neuropathy, cilioretinal artery occlusion, and central retinal vein occlusion in a haemodialysis patient. Eye 2007;21:129–30. https://doi.org/10.1038/sj.eye.6702445.Search in Google Scholar PubMed

7. Kim, DY, Silverman, RH, Chan, RVP, Khanifar, AA, Rondeau, M, Lloyd, H, et al.. Measurement of choroidal perfusion and thickness following systemic sildenafil. Viagra(R) Acta Ophthalmol. 2013;91:183–8. https://doi.org/10.1111/j.1755-3768.2011.02305.x.Search in Google Scholar PubMed PubMed Central

8. Vance, SK, Imamura, Y, Freund, KB. The effects of sildenafil citrate on choroidal thickness as determined by enhanced depth imaging optical coherence tomography. Retina 2011;31:332–5. https://doi.org/10.1097/IAE.0b013e3181eef0ae.Search in Google Scholar PubMed

9. Pache, M, Peter, M, Christian, P, Selim, O, Ines, N, Josef, F. Sildenafil induces retinal vasodilatation in healthy subjects. Br J Ophthalmol 2002;86:156–8. https://doi.org/10.1136/bjo.86.2.156.Search in Google Scholar PubMed PubMed Central

10. Montorio, D, D’Andrea, L, Cennamo, G. Retinal vascular features in ocular blunt trauma by optical coherence tomography angiography. J Clin Med 2020;9:3329. https://doi.org/10.3390/jcm9103329.Search in Google Scholar PubMed PubMed Central

11. Wang, J, Jiang, J, Zhang, Y, Qian, YW, Zhang, JF, Wang, ZL. Retinal and choroidal vascular changes in coronary heart disease: an optical coherence tomography angiography study. Biomed Opt Express 2019;10:1532. https://doi.org/10.1364/boe.10.001532.Search in Google Scholar PubMed PubMed Central

12. Chiosi, F, Rinaldi, M, Campagna, G, Manzi, G, De Angelis, V, Calabrò, F, et al.. Effect of a fixed combination of curcumin, artemisia, bromelain, and black pepper oral administration on optical coherence tomography angiography indices in patients with diabetic macular edema. Nutrients 2022;14:1520. https://doi.org/10.3390/nu14071520.Search in Google Scholar PubMed PubMed Central

13. Mónica, FZ, De Nucci, G. Tadalafil for the treatment of benign prostatic hyperplasia. Expert Opin Pharmacother 2019;20:929–37. https://doi.org/10.1080/14656566.2019.1589452.Search in Google Scholar PubMed

14. Coscas, F, Coscas, G, Zucchiatti, I, Bandello, F, Soubrane, G, Souïed, E. Optical coherence tomography in tadalafil-associated retinal toxicity. Eur J Ophthalmol 2012;22:853–6. https://doi.org/10.5301/ejo.5000127.Search in Google Scholar PubMed

15. Cennamo, G, Montorio, D, D’Alessandro, A, Napolitano, P, D’Andrea, L, Tranfa, F. Prospective study of vessel density by optical coherence tomography angiography after intravitreal bevacizumab in exudative age-related macular degeneration. Ophthalmol Ther 2020;9:77–85. https://doi.org/10.1007/s40123-019-00221-0.Search in Google Scholar PubMed PubMed Central

16. Jia, Y, Tan, O, Tokayer, J, Potsaid, B, Wang, Y, Liu, JJ, et al.. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express 2012;20:4710. https://doi.org/10.1364/oe.20.004710.Search in Google Scholar PubMed PubMed Central

17. Huang, D, Jia, Y, Gao, SS, Lumbroso, B, Rispoli, M. Optical coherence tomography angiography using the Optovue device. Dev Ophthalmol 2016;56:6–12. https://doi.org/10.1159/000442770.Search in Google Scholar PubMed

18. Moein, HR, Novais, EA, Rebhun, CB, Cole, ED, Louzada, RN, Witkin, AJ, et al.. Optical coherence tomography angiography to detect macular capillary ischemia in patients with inner retinal changes after resolved diabetic macular edema. Retina 2018;38:2277–84. https://doi.org/10.1097/iae.0000000000001902.Search in Google Scholar PubMed

19. Rao, HL, Pradhan, ZS, Weinreb, RN, Reddy, HB, Riyazuddin, M, Dasari, S, et al.. Regional comparisons of optical coherence tomography angiography vessel density in primary open-angle glaucoma. Am J Ophthalmol 2016;171:75–83. https://doi.org/10.1016/j.ajo.2016.08.030.Search in Google Scholar PubMed

20. Zhang, M, Hwang, TS, Campbell, JP, Bailey, ST, Wilson, DJ, Huang, D, et al.. Projection-resolved optical coherence tomographic angiography. Biomed Opt Express 2016;7:816–28. https://doi.org/10.1364/boe.7.000816.Search in Google Scholar

21. Wang, J, Zhang, M, Hwang, TS, Bailey, ST, Huang, D, Wilson, DJ, et al.. Reflectance-based projection-resolved optical coherence tomography angiography [Invited]. Biomed Opt Express 2017;8:1536–48. https://doi.org/10.1364/boe.8.001536.Search in Google Scholar

22. Montorio, D, D’Andrea, L, Mirto, N, Cennamo, G. The role of optical coherence tomography angiography in reticular pseudodrusen. Photodiagnosis Photodyn Ther 2021;33:102094. https://doi.org/10.1016/j.pdpdt.2020.102094.Search in Google Scholar PubMed

23. Marmor, MF, Kessler, R. Sildenafil (viagra) and ophthalmology. Surv Ophthalmol 1999;44:153–62. https://doi.org/10.1016/S0039-6257(99)00079-X.Search in Google Scholar

24. Liu, B, Zhu, L, Zhong, J, Zeng, G, Deng, T. The association between phosphodiesterase type 5 inhibitor use and risk of non-arteritic anterior ischemic optic neuropathy: a systematic review and meta-analysis. Sex. Med 2018;6:185–92. https://doi.org/10.1016/j.esxm.2018.03.001.Search in Google Scholar PubMed PubMed Central

25. Li, AS, Pomeranz, HD. Food and drug administration adverse event reports of retinal vascular occlusions associated with phosphodiesterase type 5 inhibitor use. J Neuro Ophthalmol 2016;36:480–1. https://doi.org/10.1097/WNO.0000000000000450.Search in Google Scholar PubMed

26. Vance, SK, Imamura, Y, Freund, KB. The effects of sildenafil citrate on choroidal thickness as determined by enhanced depth imaging optical coherence tomography. Retina 2011;31:332–5. https://doi.org/10.1097/IAE.0b013e3181eef0ae.Search in Google Scholar PubMed

27. Yiu, G, Vuong, VS, Tran, S, Migacz, J, Cunefare, D, Farsiu, S, et al.. Vascular response to sildenafil citrate in aging and age-related macular degeneration. Sci Rep 2019;9:5049. https://doi.org/10.1038/s41598-019-41509-2.Search in Google Scholar PubMed PubMed Central

28. Aslan, F, Topcuoğlu, M, Öktem, ÇĞ, Akkoç, A, Uçar, M. Can subfoveal choroidal thickness replace subjective tests in pa-tients using tadalafil to treat erectile dysfunction? Andrologia 2020;52:332–5. https://doi.org/10.1111/and.13580.Search in Google Scholar PubMed

29. Capece, M, Montorio, D, Comune, C, Aveta, A, Melchionna, A, Celentano, G, et al.. Retinal and optic disc vascular changes in patients using long-term tadalafil: a prospective non-randomized matched-pair study. Diagnostics 2021;11:802. https://doi.org/10.3390/diagnostics11050802.Search in Google Scholar PubMed PubMed Central

30. Lee, WJ, Seong, M. Sildenafil citrate and choroidal thickness. Retina 2011;31:1742. https://doi.org/10.1097/IAE.0b013e3182246e46.Search in Google Scholar PubMed

31. Harris, A, Kagemann, L, Ehrlich, R, Ehrlich, Y, Lopez, CR, Purvin, V. The effect of sildenafil on ocular blood flow. Br J Ophthalmol 2008;92:469–73. https://doi.org/10.1136/bjo.2007.131789.Search in Google Scholar PubMed

32. Pomeranz, HD. Erectile dysfunction agents and nonarteritic anterior ischemic optic neuropathy. Neurol Clin 2017;35:17–27. https://doi.org/10.1016/j.ncl.2016.08.007.Search in Google Scholar PubMed

33. Sabaner, MC, Dogan, M, Akdogan, M, Karadag, S, Onur, IU, Tasci, Aİ, et al.. Evaluation of retinal and choroidal microcirculation alterations after a single dose of oral 5-mg tadalafil: a prospective pilot optical coherence tomography angiography study. J Ocul Pharmacol Ther 2021;37:421–9. https://doi.org/10.1089/jop.2020.0124.Search in Google Scholar PubMed

Received: 2024-09-09
Accepted: 2024-10-10
Published Online: 2024-11-13

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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