Research Article
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Choroidal Thickness in Patients Using Hydroxychloroquine Without Retinal Toxicity

Year 2020, Volume: 2 Issue: 3, 73 - 78, 29.10.2019

Abstract

Objective: Hydroxychloroquine is a well-known antirheumatic drug that may cause irreversible retinal damage if not detected earlier. However, to date, there has been no study investigating the effects of hydroxychloroquine on the choroid. In this study, we evaluated the submacular choroidal thickness in patients using hydroxychloroquine without retinal toxicity in comparison to healthy controls.

Material and Method: Thirty patients using hydroxychloroquine, and thirty-nine healthy controls were included in this study. Only the right eyes of the patients and the control subjects were used in the analysis. The demographic features of the patients and control subjects were recorded. Each subject underwent ophthalmological examinations including refraction, visual acuity, intraocular pressure, 10/2 visual field testing, slit-lamp biomicroscopy, and fundus examination. As the last step submacular choroid was imaged by enhanced depth imaging optical coherence tomography (EDI-OCT), and measured manually at five regions (subfoveal, nasal 500, nasal 1500, temporal 500 and temporal 1500).

Results: There were no significant differences between patients and controls regarding age, gender, intraocular pressure, best-corrected visual acuity (p>0,05). Choroidal thickness values at all regions were statistically higher in patients than controls (subfoveal; p < 0.05, nasal 500; p < 0.01, nasal 1500; p < 0.01, temporal 500; p < 0.01,temporal 1500; p < 0.01). The mean of the subfoveal choroidal thickness is 319.2 ± 79.4 in patients and 270.3 ± 102.4 in controls. It is 314.3 ± 84.7 vs 253.7 ± 94.8 for nasal 500, 288 ± 90.1 vs 219.8 ± 84.4 for nasal 1500, 313.9 ± 76.1 vs 254.4 ± 90.9 for temporal 500 and 288.6 ± 61.3 vs 240.9 ± 90.7 for temporal 1500.


Conclusion:
Thickening in submacular choroid could be due to the accumulation of these drugs in the choroidal melanocytes and reactions from the surrounding tissues.

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Thanks

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References

  • Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF, Lum F. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016. doi:10.1016/j.ophtha.2016.01.058
  • Marmor MF, Kellner U, Lai TYY, Lyons JS, Mieler WF. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011;118(2):415-422. doi:10.1016/j.ophtha.2010.11.017
  • Korthagen NM, Bastiaans J, van Meurs JC, van Bilsen K, van Hagen PM, Dik WA. Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015. doi:10.1002/jbt.21696
  • Pikkel J, Chassid O, Sharabi-Nov A, Beiran I. A retrospective evaluation of the effect of hydroxyquinine on RPE thickness. Graefe’s Arch Clin Exp Ophthalmol. 2013. doi:10.1007/s00417-012-2256-5
  • Lee MG, Kim SJ, Ham D Il, et al. Macular retinal ganglion cell–inner plexiform layer thickness in patients on hydroxychloroquine therapy. Investig Ophthalmol Vis Sci. 2015. doi:10.1167/iovs.14-15138
  • De Sisternes L, Hu J, Rubin DL, Marmor MF. Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: Inner versus outer retina, parafovea versus peripheral fovea. Investig Ophthalmol Vis Sci. 2015. doi:10.1167/iovs.14-16345
  • Marmor MF. Comparison of screening procedures in hydroxychloroquine toxicity. Arch Ophthalmol. 2012. doi:10.1001/archophthalmol.2011.371
  • Eibl O, Schultheiss S, Blitgen-Heinecke P, Schraermeyer U. Quantitative chemical analysis of ocular melanosomes in the TEM. Micron. 2006. doi:10.1016/j.micron.2005.08.006
  • Schroeder RL, Gerber JP. Chloroquine and hydroxychloroquine binding to melanin: Some possible consequences for pathologies. Toxicol Reports. 2014;1:963-968. doi:10.1016/j.toxrep.2014.10.019
  • Seo S, Lee CE, Jeong JH, Park KH, Kim DM, Jeoung JW. Ganglion cell-inner plexiform layer and retinal nerve fiber layer thickness according to myopia and optic disc area: A quantitative and three-dimensional analysis. BMC Ophthalmol. 2017;17(1):1-8. doi:10.1186/s12886-017-0419-1
  • Marneros AG, Fan J, Yokoyama Y, et al. Vascular endothelial growth factor expression in the retinal pigment epithelium is essential for choriocapillaris development and visual function. Am J Pathol. 2005. doi:10.1016/S0002-9440(10)61231-X
  • Ahn SJ, Ryu SJ, Joung JY, Lee BR. Choroidal Thinning Associated With Hydroxychloroquine Retinopathy. Am J Ophthalmol. 2017;183:56-64. doi:10.1016/j.ajo.2017.08.022
  • Tsang AC, Ahmadi Pirshahid S, Virgili G, Gottlieb CC, Hamilton J, Coupland SG. Hydroxychloroquine and chloroquine retinopathy: A systematic review evaluating the multifocal electroretinogram as a screening test. Ophthalmology. 2015. doi:10.1016/j.ophtha.2015.02.011
  • Marmor MF, Melles RB. Disparity between visual fields and optical coherence tomography in hydroxychloroquine retinopathy. Ophthalmology. 2014. doi:10.1016/j.ophtha.2013.12.002
  • Read SA, Collins MJ, Vincent SJ, Alonso-Caneiro D. Choroidal thickness in childhood. Invest Ophthalmol Vis Sci. 2013. doi:10.1167/iovs.13-11732
  • Hirata M, Tsujikawa A, Matsumoto A, et al. Macular choroidal thickness and volume in normal subjects measured by swept-source optical coherence tomography. Investig Ophthalmol Vis Sci. 2011. doi:10.1167/iovs.11-7729
  • Manjunath V, Taha M, Fujimoto JG, Duker JS. Choroidal thickness in normal eyes measured using cirrus HD optical coherence tomography. Am J Ophthalmol. 2010. doi:10.1016/j.ajo.2010.04.018
  • Margolis R, Spaide RF. A Pilot Study of Enhanced Depth Imaging Optical Coherence Tomography of the Choroid in Normal Eyes. Am J Ophthalmol. 2009. doi:10.1016/j.ajo.2008.12.008
  • Ahn SJ, Joung J, Lee BR. En Face Optical Coherence Tomography Imaging of the Photoreceptor Layers in Hydroxychloroquine Retinopathy. Am J Ophthalmol. 2019;199:71-81. doi:10.1016/j.ajo.2018.11.003
  • Bardak Y, Cekic O. Sistemik Hidroksiklorokin Kullan ı m ı ve Erken Evre Maküla Fonksiyon De ğ i ş imleri. Retina-Vitreus. 2007;15:111-114.
  • Ferreira CS, Beato J, Falcão MS, Brandão E, Falcão-Reis F, Carneiro ÂM. Choroidal thickness in multisystemic autoimmune diseases without ophthalmologic manifestations. In: Retina. ; 2017. doi:10.1097/IAE.0000000000001193
  • Karti O, Ayhan Z, Zengin MO, Kaya M, Kusbeci T. Choroidal Thickness Changes in Rheumatoid Arthritis and the Effects of Short-term Hydroxychloroquine Treatment. Ocul Immunol Inflamm. 2018;26(5):770-775. doi:10.1080/09273948.2017.1278777
  • Gökmen O, Yeşilırmak N, Akman A, et al. Corneal, scleral, choroidal, and foveal thickness in patients with rheumatoid arthritis. Turkish J Ophthalmol. 2017;47(6):315-319. doi:10.4274/tjo.58712

Hidroksiklorokin Kullanan Retinal Toksisite Gelişmemiş Hastalarda Koroid Kalınlığı

Year 2020, Volume: 2 Issue: 3, 73 - 78, 29.10.2019

Abstract

Amaç: Hidroksiklorokin erken dönemde tespit edilmezse kalıcı retinal hasara sebep olabilen, iyi bilinen, antiromatizmal bir ilaçtır. Buna rağmen koroid tabakasına etkisini araştıran herhangi bir çalışma bulunmamaktadır. Bu çalışmada biz hidroksiklorokinin submaküler koroid kalınlığına etkisini değerlendirmeyi amaçladık.


Gereç ve Yöntem:
Otuz hidroksiklorokin kullanan hasta ve otuz dokuz sağlıklı kontrol çalışmaya dahil edildi. Analizlerde yalnızca sağ gözler kullanıldı. Hasta ve kontrollerin demografik verileri kayıt edildi. Tüm hastaların refraksiyon, görme keskinliği, göz içi basıncı, 10-2 görme alanı testi, biyomikroskopi ve fundoskopik muayenelerini içeren oftalmolojik muayene bulguları kayıt edildi. Son olarak ise submaküler koroid kalınlığı arttırılmış derinlik görüntüleme-optik koherens tomografi (EDI-OKT) yöntemi ile 5 noktadan (subfoveal, nazal500, nazal1500, temporal500 ve temporal1500) ölçüldü.

Bulgular: Yaş, cinsiyet, göz içi basıncı ve görme keskinliği açısından gruplar arası anlamlı fark yoktu (P > 0,05). Ölçüm yapılan tüm noktalarda koroid kalınlığı hidroksiklorokin kullananlarda kontrollere göre istatiksel daha kalın idi (subfoveal; p < 0,05, nazal 500; p < 0,01, nazal 1500; p < 0,01, temporal 500; p < 0,01,temporal 1500; p < 0,01). Hasta grubunda subfoveal ortalama koroid kalınlığı 319,2 ± 79,4 idi, kontrol grubunda ise 270.3 ± 102.4 idi. Nazal 500 noktasında 314,3 ± 84,7’a karşılık 253,7 ± 94,8, nazal 1500 noktasında 288 ± 90,1’a karşılık 219,8 ± 84,4, temporal 500 noktasında 313,9 ± 76,1’a karşılık 254,4 ± 90,9 ve temporal 1500 noktasında 288,6 ± 61,3’a karşılık 240,9 ± 90,7 idi.


Sonuç:
Submaküler koroidin kalınlaşması hidroksiklorokinin koroidal melanositlerde birikmesine ve çevre dokudaki reksiyona bağlı olabilir. Bu hipotezin doğrulanabilmesi için deneysel çalışmalar gerekmektedir.

Project Number

-

References

  • Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF, Lum F. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016. doi:10.1016/j.ophtha.2016.01.058
  • Marmor MF, Kellner U, Lai TYY, Lyons JS, Mieler WF. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011;118(2):415-422. doi:10.1016/j.ophtha.2010.11.017
  • Korthagen NM, Bastiaans J, van Meurs JC, van Bilsen K, van Hagen PM, Dik WA. Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015. doi:10.1002/jbt.21696
  • Pikkel J, Chassid O, Sharabi-Nov A, Beiran I. A retrospective evaluation of the effect of hydroxyquinine on RPE thickness. Graefe’s Arch Clin Exp Ophthalmol. 2013. doi:10.1007/s00417-012-2256-5
  • Lee MG, Kim SJ, Ham D Il, et al. Macular retinal ganglion cell–inner plexiform layer thickness in patients on hydroxychloroquine therapy. Investig Ophthalmol Vis Sci. 2015. doi:10.1167/iovs.14-15138
  • De Sisternes L, Hu J, Rubin DL, Marmor MF. Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: Inner versus outer retina, parafovea versus peripheral fovea. Investig Ophthalmol Vis Sci. 2015. doi:10.1167/iovs.14-16345
  • Marmor MF. Comparison of screening procedures in hydroxychloroquine toxicity. Arch Ophthalmol. 2012. doi:10.1001/archophthalmol.2011.371
  • Eibl O, Schultheiss S, Blitgen-Heinecke P, Schraermeyer U. Quantitative chemical analysis of ocular melanosomes in the TEM. Micron. 2006. doi:10.1016/j.micron.2005.08.006
  • Schroeder RL, Gerber JP. Chloroquine and hydroxychloroquine binding to melanin: Some possible consequences for pathologies. Toxicol Reports. 2014;1:963-968. doi:10.1016/j.toxrep.2014.10.019
  • Seo S, Lee CE, Jeong JH, Park KH, Kim DM, Jeoung JW. Ganglion cell-inner plexiform layer and retinal nerve fiber layer thickness according to myopia and optic disc area: A quantitative and three-dimensional analysis. BMC Ophthalmol. 2017;17(1):1-8. doi:10.1186/s12886-017-0419-1
  • Marneros AG, Fan J, Yokoyama Y, et al. Vascular endothelial growth factor expression in the retinal pigment epithelium is essential for choriocapillaris development and visual function. Am J Pathol. 2005. doi:10.1016/S0002-9440(10)61231-X
  • Ahn SJ, Ryu SJ, Joung JY, Lee BR. Choroidal Thinning Associated With Hydroxychloroquine Retinopathy. Am J Ophthalmol. 2017;183:56-64. doi:10.1016/j.ajo.2017.08.022
  • Tsang AC, Ahmadi Pirshahid S, Virgili G, Gottlieb CC, Hamilton J, Coupland SG. Hydroxychloroquine and chloroquine retinopathy: A systematic review evaluating the multifocal electroretinogram as a screening test. Ophthalmology. 2015. doi:10.1016/j.ophtha.2015.02.011
  • Marmor MF, Melles RB. Disparity between visual fields and optical coherence tomography in hydroxychloroquine retinopathy. Ophthalmology. 2014. doi:10.1016/j.ophtha.2013.12.002
  • Read SA, Collins MJ, Vincent SJ, Alonso-Caneiro D. Choroidal thickness in childhood. Invest Ophthalmol Vis Sci. 2013. doi:10.1167/iovs.13-11732
  • Hirata M, Tsujikawa A, Matsumoto A, et al. Macular choroidal thickness and volume in normal subjects measured by swept-source optical coherence tomography. Investig Ophthalmol Vis Sci. 2011. doi:10.1167/iovs.11-7729
  • Manjunath V, Taha M, Fujimoto JG, Duker JS. Choroidal thickness in normal eyes measured using cirrus HD optical coherence tomography. Am J Ophthalmol. 2010. doi:10.1016/j.ajo.2010.04.018
  • Margolis R, Spaide RF. A Pilot Study of Enhanced Depth Imaging Optical Coherence Tomography of the Choroid in Normal Eyes. Am J Ophthalmol. 2009. doi:10.1016/j.ajo.2008.12.008
  • Ahn SJ, Joung J, Lee BR. En Face Optical Coherence Tomography Imaging of the Photoreceptor Layers in Hydroxychloroquine Retinopathy. Am J Ophthalmol. 2019;199:71-81. doi:10.1016/j.ajo.2018.11.003
  • Bardak Y, Cekic O. Sistemik Hidroksiklorokin Kullan ı m ı ve Erken Evre Maküla Fonksiyon De ğ i ş imleri. Retina-Vitreus. 2007;15:111-114.
  • Ferreira CS, Beato J, Falcão MS, Brandão E, Falcão-Reis F, Carneiro ÂM. Choroidal thickness in multisystemic autoimmune diseases without ophthalmologic manifestations. In: Retina. ; 2017. doi:10.1097/IAE.0000000000001193
  • Karti O, Ayhan Z, Zengin MO, Kaya M, Kusbeci T. Choroidal Thickness Changes in Rheumatoid Arthritis and the Effects of Short-term Hydroxychloroquine Treatment. Ocul Immunol Inflamm. 2018;26(5):770-775. doi:10.1080/09273948.2017.1278777
  • Gökmen O, Yeşilırmak N, Akman A, et al. Corneal, scleral, choroidal, and foveal thickness in patients with rheumatoid arthritis. Turkish J Ophthalmol. 2017;47(6):315-319. doi:10.4274/tjo.58712
There are 23 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Articles
Authors

Hayati Yılmaz 0000-0001-5051-5713

Dorukcan Akıncıoğlu This is me 0000-0001-6409-9802

Murat Küçükevcilioğlu 0000-0001-7776-2183

Gökhan Özge 0000-0003-0943-8917

Ali Durukan This is me 0000-0001-6571-6155

Fm Mutlu 0000-0002-7796-6511

Project Number -
Publication Date October 29, 2019
Submission Date September 17, 2020
Acceptance Date October 20, 2020
Published in Issue Year 2020 Volume: 2 Issue: 3

Cite

AMA Yılmaz H, Akıncıoğlu D, Küçükevcilioğlu M, Özge G, Durukan A, Mutlu F. Choroidal Thickness in Patients Using Hydroxychloroquine Without Retinal Toxicity. Hitit Medical Journal. October 2019;2(3):73-78.