HİDROKSİKLOROKİN KULLANIMININ RETİNA VE KOROİD ÜZERİNE ETKİLERİNİN DEĞERLENDİRİLMESİ: RETROSPEKTİF OCT ÇALIŞMASI

Öz

Amaç: Bu çalışmada hidroksiklorokin (HK) tedavisi gören ve belirgin retinal toksisitesi olmayan hastalarda retina, koroid ve koroid vaskülaritesinde etkilenme olup olmadığı araştırılmıştır. Gereç ve Yöntemler: Çalışmamız, HK tedavisi gören 51 hasta ve 24 sağlıklı gönüllü olmak üzere toplam 75 kişinin dâhil edildiği retrospektif vaka kontrol çalışmasıdır. Hasta grup, 5 yıldan az HK kullananlar (grup 1, 30 hasta) ile 5 yıl ve daha fazla HK kullananlar (grup 2, 21 hasta) olmak üzere iki grupta incelendi. Tüm katılımcıların oftalmolojik muayene raporları ve optik koherens tomografi (OKT) görüntüleri tarandı. HK’ye bağlı belirgin retinal toksisitesi bulunan hastalar çalışmaya dâhil edilmedi. OKT görüntülerinden alınan; peripapiller, foveal ve parafoveal retina tabakaları kalınlıkları, subfoveal koroid kalınlıkları ile koroid vaskülarite indeksi (KVİ) ölçümleri hesaplanarak kaydedildi. Bulgular: HK kullanan hastalarda subfoveal koroid kalınlığı her 2 grupta kontrol grubuna kıyasla anlamlı şekilde azalmıştır (sırasıyla p=0,035 ve p=0,014). Makular alanda 1-3 mm zonda inferior ve nazal parafoveal retina sinir lifi tabakası (RSLT), temporal parafoveal gangliyon hücre tabakası ve iç pleksiform tabaka kalınlıkları azalırken, temporal parafoveal retina pigment epitel tabakası kalınlıkları artmıştır. Peripapiller-RSLT ve KVİ ölçümlerinde gruplar arasında anlamlı bir farklılık görülmemiştir (p>0,05). Sonuç:Çalışmamız, HK kullanan ve belirgin bir retinal toksisitesi olmayan hastaların, retina ve koroid kalınlık ölçümlerinde bazı değişiklikler olduğunu göstermiştir. Gelecekte yapılacak daha geniş kapsamlı ve uzunlamasına klinik çalışmalar ile bu değişikliklerin, HK kullanan hastaların takibinde, retinopatinin erken tanısı için klinik belirteçler olarak kullanılabileceğini düşünmekteyiz.

Anahtar Kelimeler

• Hidroksiklorokin
• retina
• koroid
• retina sinir lifi tabakası
• optik koherans tomografi

Evaluation of the Effects of Hydroxychloroquine Use on Retina and Choroid: A Retrospective OCT Study

Öz

Objective: In this study we investigated whether retinal, choroidal and choroidal vascularity were affected in patients treated with hydroxychloroquine (HC) without significant retinal toxicity. Material and Methods: Our study was a retrospective case-control study in which 51 patients and 24 healthy volunteers were included. The patient group was divided into two groups: those who used HC for less than 5 years (group 1, 30 patients) and those who used HC for 5 years or more (group 2, 21 patients). Ophthalmologic examination reports and optical coherence tomography (OCT) images of all participants were scanned. Patients with significant retinal toxicity due to HC were excluded from the study. Peripapillary, foveal and parafoveal retinal layer thickness, subfoveal choroidal thickness and choroidal vascularity index (CVI) measurements were calculated and recorded from OCT images. Results: Subfoveal choroidal thickness was significantly reduced in both groups compared to the control group in HC groups (p=0.035 and p=0.014, respectively). In the macular area, inferior and nasal parafoveal retinal nerve fiber layer (RNFL), temporal parafoveal ganglion cell layer and inner plexiform layer thicknesses decreased, while temporal parafoveal retinal pigment epithelial layer thickness increased in the 1-3 mm zone. There was no significant difference between the groups in peripapillary-RNFL and CVI measurements (p>0.05). Conclusion:Our study showed that there were some changes in retinal and choroidal thickness measurements in patients who used HC without any significant retinal toxicity. With further clinical studies, we think that these changes can be used as clinical markers for the early diagnosis of retinopathy in the follow-up of patients using HC.

Anahtar Kelimeler

• Hydroxychloroquine
• retina
• choroid
• retinal nerve fiber layer
• optical coherence tomography

Kaynakça

1. Marmor MF, Carr RE, Easterbrook M, et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: A report by the American Academy of Ophthalmology. Ophthalmology. 2002;109:1377-1382.
2. Marmor MF, Kellner U, Lai TY, et al. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011;118:415-422.
3. Marmor MF, Kellner U, Lai TY, et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123:1386-1394.
4. Lally DR, Heier JS, Baumal C, et al. Expanded spectral domain-OCT findings in the early detection of hydroxychloroquine retinopathy and changes following drug cessation. Int. J. Retina Vitreous. 2016;2:18.
5. Mititelu M, Wong BJ, Brenner M, Bryar PJ, Jampol LM, Fawzi AA. Progression of hydroxychloroquine toxic effects after drug therapy cessation: New evidence from multimodal imaging. JAMA Ophthalmol. 2013;131(9):1187-1197
6. Marmor MF, Hu J. Effect of disease stage on progression of hydroxychloroquine retinopathy. JAMA Ophthalmol. 2014;132(9):1105-1112.
7. Bulut M, Erol MK, Toslak D, Akidan M, Kaya Başar E, Çay HF. A new objective parameter in hydroxychloroquine-induced retinal toxicity screening test: Macular retinal ganglion cell-inner plexiform layer thickness. Arch Rheumatol. 2017;33(1):52-58.
8. de Sisternes L, Hu J, Rubin DL, Marmor MF. Analysis of inner and outer retinal thickness in patients using hydroxychloroquine prior to development of retinopathy. JAMA Ophthalmol. 2016;134(5):511-519

9. Modi YS, Au A, Parikh VS, Ehlers JP, Schachat AP, Singh RP. Volumetric single-layer inner retinal analysis in patients with hydroxychloroquine toxicity, Retina. 2016;36(10):1941-1950.
10. Agrawal R, Gupta P, Tan KA, Cheung CM, Wong TY, Cheng CY. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study. Sci Rep. 2016;6:21090.
11. Cay HF, Erol MK, Çoban DT, et al. Retinotoxicity of hydroxychloroquine: Is it possible to demonstrate by spectral domain optical coherence tomography before development? A cross sectional investigation. Arch. Rheumatol. 2014;29(3):178-185.
12. Yulek F, Ugurlu N, Akcay E, et al. Early retinal and retinal nerve fiber layer effects of hydroxychloroquine: A follow up study by sdOCT. Cutan. Ocul. Toxicol. 2013;32(3):204-209.
13. Allam RS, Abd-Elmohsen MN, Khafagy MM, Raafat KA, Sheta SM. Spectral-domain optical coherence tomography of preclinical chloroquine maculopathy in egyptian rheumatoid arthritis patients. J Ophthalmol. 2015;2015:292357.
14. Antunes Dde A, Cavalcanti HD, Leal D, et al. Retinal nerve fiber layer alteration in chronic users of chloroquine. Arq. Bras. Oftalmol. 2005;68(2):195-197.
15. Arana LA, Arana J, Hasimoto AR, et al. Optical coherence tomography to evaluate peripapillary retinal nerve fiber layer in chloroquine patients. Arq. Bras. Oftalmol. 2010;73(1):28-32.
16. Bonanomi MT, Dantas NC, Medeiros FA. Retinal nerve fibre layer thickness measurements in patients using chloroquine. Clin. Exp. Ophthalmol. 2006;34(2):130-136.
17. Pasadhika S, Fishman GA. Effects of chronic exposure to hydroxychloroquine or chloroquine on inner retinal structures. Eye. 2010;24(2):340-346.
18. Lee MG, Kim SJ, Ham DI, et al. Macular retinal ganglion cell-inner plexiform layer thickness in patients on hydroxychloroquine therapy. Invest. Ophthalmol. Vis. Sci. 2014;56(1):396-402.
19. Pasadhika S, Fishman GA, Choi D, Shahidi M. Selective thinning of the perifoveal inner retina as an early sign of hydroxychloroquine retinal toxicity, Eye. 2010;24(5):756-762.
20. Kan E, Yakar K, Demirag MD, Gok M. Macular ganglion cell-inner plexiform layer thickness for detection of early retinal toxicity of hydroxychloroquine. Int. Ophthalmol. 2018;38(4):1635-1640.
21. Yoshida T, Fukatsu R, Tsuzuki K, et al. Amyloid precursor protein, Aβ and amyloid-associated proteins involved in chloroquine retinopathy in rats-immunopathological studies. Brain Res. 1997;764(1-2):283-288.
22. Pikkel J, Chassid O, Sharabi-Nov A, Beiran I. A retrospective evaluation of the effect of hydroxyquinine on RPE thickness. Graef’s Arch. Clin. Exp. 2013;251(7):1687-1690.
23. Uslu H, Gurler B, Yildirim A, et al. Effect of hydroxychloroquine on the retinal layers: A quantitative evaluation with spectral-domain optical coherence tomography, J. Ophthalmol. 2016;8643174.
24. Martín-Iglesias D, Artaraz J, Fonollosa A, Ugarte A, Arteagabeitia A, Ruiz-Irastorza G. Evolution of retinal changes measured by optical coherence tomography in the assessment of hydroxychloroquine ocular safety in patients with systemic lupus erythematosus. Lupus. 2019;28(4):555-559.
25. Mahon GJ, Anderson HR, Gardiner TA, McFarlane S, Archer DB, Stitt AW. Chloroquine causes lysosomal dysfunction in neural retina and RPE: Implications for retinopathy, Curr. Eye Res. 2004;28(4):277-284.
26. Ahn SJ, Ryu SJ, Joung JY, Lee BR. Choroidal thinning associated with hydroxychloroquine retinopathy, Am. J. Ophthalmol. 2017;183:56-64.