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Retinitis pigmentozalı hastalarda trombositten zengin plazma enjeksiyon uygulamaları

Year 2022, Volume: 15 Issue: 1, 29 - 37, 30.04.2022
https://doi.org/10.26559/mersinsbd.967974

Abstract

Amaç: Retinitis Pigmentozalı (RP) hastalarda subtenon otolog trombositten zengin plazma (PRP) enjeksiyonun görme keskinliği, görme alanı ve görmeye bağlı yaşam kalitesine (YK) etkisini değerlendirmektir. Yöntem: Bu retrospektif çalışmada, 2019-2021 tarihleri arasında 31 RP’li hastanın 60 gözüne iki haftalık aralıklarla üç defa subtenon otolog PRP enjeksiyonu uygulandı. PRP öncesi ve PRP enjeksiyonlarından bir ay sonra en iyi düzeltilmiş görme keskinlikleri (EİDGK) ve görme alanı değerleri [(mean deviation (MD) ve pattern standard deviation (PSD)] karşılaştırıldı. Bu hastalardan takiplerine devam eden 19’unun 36 gözüne son enjeksiyondan altı ay sonra ilave enjeksiyon uygulandı. Bu grupta PRP öncesi ve ilave enjeksiyon sonrası EİDGK, görme alanı değerleri ve görmeye bağlı YK puanları karşılaştırıldı. Bulgular: Ortanca (Q1-Q3) değerleri EİDGK için, PRP’den önce 0.80 (0.52-1.30) logMAR, sonra 0.80 (0.50-1.28) logMAR, MD için, önce -30.26 (-31.10 – -28.56), sonra -29.79 (-31.13 – -28.61) , PSD için, önce 6.27 (4.78 – 8.15) , sonra 6.59 (4.90 – 8.06) idi. EİDGK ve MD değerleri için aradaki fark istatistiksel olarak anlamlı idi (p<0.001, p=0.037, sırayla). İlave enjeksiyon yapılan grupta ilk PRP enjeksiyonu öncesi ve ilave enjeksiyon sonrası EİDGK ve görmeye bağlı YK için aradaki fark istatistiksel olarak anlamlı , MD için anlamlı değildi (p<0.005;p<0.001; p=0.393;sırayla). Uygulamayla ilişkili oftalmolojik ve sistemik bir komplikasyon görülmedi. Sonuç: Subtenon otolog PRP enjeksiyonunun, Retinitis pigmentozalı hastalarda görsel fonksiyonlar ve yaşam kalitesi üzerinde olumlu etkisi olabilir. Ancak tedavinin etkililiği ve uygulama sıklığının belirlenmesi için daha geniş katılımlı ve daha uzun takip süreli çalışmalara ihtiyaç vardır.

References

  • Bird AC. Retinal photoreceptor dystrophies LI. Edward Jackson Memorial Lecture. Am J Ophthalmol. 1995;119(5):543-562. doi:10.1016/s0002-9394(14)70212-0.
  • Sainohira M, Yamashita T, Terasaki H, Sonoda S, Miyata K, Murakami Y et al. Quantitative analyses of factors related to anxiety and depression in patients with retinitis pigmentosa. PLoS One. 2018;13(4):e0195983. doi:10.1371/journal.pone.0195983.
  • Li Y, Wu WH, Hsu CW, Nguyen HV, Tsai YT, Chan L et al. Gene therapy in patient-specific stem cell lines and a preclinical model of retinitis pigmentosa with membrane frizzled-related protein defects. Mol Ther. 2014;22(9):1688-1697. doi:10.1038/mt.2014.100.
  • Yoshida T, Ozawa Y, Suzuki K, Yuki K, Ohyama M, Akamatsu W et al. The use of induced pluripotent stem cells to reveal pathogenic gene mutations and explore treatments for retinitis pigmentosa. Mol Brain. 2014;7:45. doi: 10.1186/1756-6606-7-45.
  • Tran BK, Wolfensberger TJ. Retina-Implant Interaction after 16 Months Follow-up in a Patient with an Argus II Prosthesis. Klin Monbl Augenheilkd. 2017;234(4):538-540. doi: 10.1055/s-0042-121660.
  • Arslan U, Özmert E, Demirel S, Örnek F, Şermet F. Effects of subtenon-injected autologous platelet-rich plasma on visual functions in eyes with retinitis pigmentosa: preliminary clinical results. Graefes Arch Clin Exp Ophthalmol. 2018;256(5):893-908. doi: 10.1007/s00417-018-3953-5.
  • Kahraman NS, Oner A. Subtenon Injection of Autologous Platelet-Rich Plasma in Retinitis Pigmentosa: Is It a New Therapeutic Option? Open Journal of Ophthalmology. 2020;10(01):77-88. doi:10.4236/ojoph.2020.101010.
  • Seo JH, Yu HG, Lee BJ. Assessment of functional vision score and vision-specific quality of life in individuals with retinitis pigmentosa. Korean J Ophthalmol. 2009 Sep;23(3):164-168. doi:10.3341/kjo.2009.23.3.164.
  • Levinson JD, Joseph E, Ward LA, Nocera JR, Pardue MT, Bruce BB et al. Physical Activity and Quality of Life in Retinitis Pigmentosa. J Ophthalmol. 2017;2017:6950642. doi: 10.1155/2017/6950642.
  • Choi SU, Chun YS, Lee JK, Kim JT, Jeong JH, Moon NJ. Comparison of vision-related quality of life and mental health between congenital and acquired low-vision patients. Eye (Lond). 2019;33(10):1540-1546. doi: 10.1038/s41433-019-0439-6.
  • Sugawara T, Hagiwara A, Hiramatsu A, Ogata K, Mitamura Y, Yamamoto S. Relationship between peripheral visual field loss and vision-related quality of life in patients with retinitis pigmentosa. Eye (Lond). 2010;24(4):535-539. doi: 10.1038/eye.2009.176.
  • Hahm BJ, Shin YW, Shim EJ, Jeon HJ, Seo JM, Chung H et al. Depression and the vision-related quality of life in patients with retinitis pigmentosa. Br J Ophthalmol. 2008;92(5):650-654. doi: 10.1136/bjo.2007.127092.
  • Chaumet-Riffaud AE, Chaumet-Riffaud P, Cariou A, Devisme C, Audo I, Sahel JA et al. Impact of Retinitis Pigmentosa on Quality of Life, Mental Health, and Employment Among Young Adults. Am J Ophthalmol. 2017;177:169-174. doi: 10.1016/j.ajo.2017.02.016.
  • Campochiaro PA, Mir TA. The mechanism of cone cell death in Retinitis Pigmentosa. Prog Retin Eye Res. 2018;62:24-37. doi: 10.1016/j.preteyeres.2017.08.004.
  • Newton F, Megaw R. Mechanisms of Photoreceptor Death in Retinitis Pigmentosa. Genes (Basel). 2020 Sep 24;11(10):1120. doi:10.3390/genes11101120.
  • Wang W, Lee SJ, Scott PA, Lu X, Emery D, Liu Y et al. Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa. Cell Rep.2016;15(2):372-385. doi:10.1016/j.celrep.2016.03.022.
  • Wong F, Kwok SY. The Survival of Cone Photoreceptors in Retinitis Pigmentosa. JAMA Ophthalmol. 2016;134(3):249-250. doi: 10.1001/jamaophthalmol.2015.5490.
  • Lee JH, Kim MJ, Ha SW, Kim HK. Autologous Platelet-rich Plasma Eye Drops in the Treatment of Recurrent Corneal Erosions. Korean J Ophthalmol. 2016;30(2):101-107. doi:10.3341/kjo.2016.30.2.101.
  • Anitua E, Muruzabal F, de la Fuente M, Merayo J, Durán J, Orive G. Plasma Rich in Growth Factors for the Treatment of Ocular Surface Diseases. Curr Eye Res. 2016;41(7):875-882. doi:10.3109/02713683.2015.1104362.
  • Di Pierdomenico J, Scholz R, Valiente-Soriano FJ, Sánchez-Migallón MC, Vidal-Sanz M, Langmann T et al. Neuroprotective Effects of FGF2 and Minocycline in Two Animal Models of Inherited Retinal Degeneration. Invest Ophthalmol Vis Sci. 2018;59(11):4392-4403. doi:10.1167/iovs.18-24621.
  • Toprak AB, Eser E, Güler C, Baser FE, Mayali H. Cross-validation of the Turkish Version of the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ 25),Ophthalmic Epidemiol. 2005;12(4):259-269. doi: 10.1080/09286580590967763.
  • Sahli E, Arslan U, Özmert E, İdil A. Evaluation of the effect of subtenon autologous platelet-rich plasma injections on visual functions in patients with retinitis pigmentosa. Regen Med. 2021;16(2):131-143. doi: 10.2217/rme-2020-0075.
  • Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int J Mol Sci.2020;21(20):7794. doi:10.3390/ijms21207794.
  • Sahel JA, Léveillard T, Picaud S, Dalkara D, Marazova K, Safran A et al. Functional rescue of cone photoreceptors in retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol. 2013;251(7):1669-1677. doi: 10.1007/s00417-013-2314-7.
  • Koenekoop RK. Why some photoreceptors die, while others remain dormant: lessons from RPE65 and LRAT associated retinal dystrophies. Ophthalmic Genet.2011;32(2):126-128. doi:10.3109/13816810.2010.544361.
  • Amable PR, Carias RB, Teixeira MV, da Cruz Pacheco I, Corrêa do Amaral RJ, Granjeiro JM et al. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. 2013;4(3):67. doi: 10.1186/scrt218.
  • Hersant B, Sid-Ahmed M, Braud L, Jourdan M, Baba-Amer Y, Meningaud JP et al. Platelet-Rich Plasma Improves the Wound Healing Potential of Mesenchymal Stem Cells through Paracrine and Metabolism Alterations. Stem Cells Int. 2019;2019:1234263. doi:10.1155/2019/1234263.
  • Mangione CM, Lee PP, Pitts J, Gutierrez P, Berry S, Hays RD. Psychometric properties of the National Eye Institute Visual Function Questionnaire (NEI-VFQ). NEI-VFQ Field Test Investigators. Arch Ophthalmol. 1998;116(11):1496-1504. doi:10.1001/archopht.116.11.1496.
  • Sugawara T, Sato E, Baba T, Hagiwara A, Tawada A, Yamamoto S. Relationship between vision-related quality of life and microperimetry-determined macular sensitivity in patients with retinitis pigmentosa. Jpn J Ophthalmol. 2011;55(6):643-646. doi: 10.1007/s10384-011-0080-9.
  • Markowitz SN. Principles Of Modern Low Vision Rehabilitation. Can J Ophthalmol. 2006;41(3): 289-312. doi: 10.1139/I06-027.
  • Giacomelli G, Virgili G, Giansanti F, Sato G, Cappello E, Cruciani F et al. Clinical and microperimetric predictors of reading speed in low vision patients: a structural equation modeling approach. Invest Ophthalmol Vis Sci. 2013;54 (6):4403–4408. doi: 10.1167/iovs.12-10734.

Platelet-rich plasma ınjection applications in patients with retinitis pigmentosa

Year 2022, Volume: 15 Issue: 1, 29 - 37, 30.04.2022
https://doi.org/10.26559/mersinsbd.967974

Abstract

Aim: To evaluate the effect of subtenon autologous platelet-rich plasma (PRP) injection on visual acuity, visual field and vision-related quality of life (QoL) in patients with Retinitis Pigmentosa (RP). Method: In this retrospective study, subtenon autologous PRP injections were applied to 60 eyes of 31 RP patients three times at two-week intervals between 2019- 2021. Best-corrected visual acuity (BCVA) and visual field values [(mean deviation (MD)) and pattern standard deviation (PSD)] were compared before and one month after PRP injections. An additional injection was applied to 36 eyes of 19 of these patients who were followed up six months after the last injection. In this group, BCVA, visual field values and vision-related QoL scores were compared before and after PRP. Results: Median (Q1- Q3) values for BCVA 0.80 (0.52- 1.30) before PRP, then 0.80 (0.50- 1.28) logMAR, for MD, first -30.26 (-31.10 – -28.56), then -29.79 (-31.13 – -28.61), for PSD, it was 6.27 (4.78 – 8.15), then 6.59 (4.90 – 8.06). The difference between BCVA and MD values was statistically significant (p <0.001, p = 0.037, respectively). The difference between BCVA and visual QoL before and after the first PRP injection in the group that received additional injections was statistically significant, but not significant for MD (p <0.005; p <0.001; p = 0.393; respectively). There were no ophthalmologic/systemic complications associated with the application. Conclusion: Subtenon autologous PRP injection may have a positive effect on visual functions and quality of life in patients with retinitis pigmentosa. However, studies with larger participation and longer follow-up periods are needed to determine the effectiveness of the treatment and the frequency of application

References

  • Bird AC. Retinal photoreceptor dystrophies LI. Edward Jackson Memorial Lecture. Am J Ophthalmol. 1995;119(5):543-562. doi:10.1016/s0002-9394(14)70212-0.
  • Sainohira M, Yamashita T, Terasaki H, Sonoda S, Miyata K, Murakami Y et al. Quantitative analyses of factors related to anxiety and depression in patients with retinitis pigmentosa. PLoS One. 2018;13(4):e0195983. doi:10.1371/journal.pone.0195983.
  • Li Y, Wu WH, Hsu CW, Nguyen HV, Tsai YT, Chan L et al. Gene therapy in patient-specific stem cell lines and a preclinical model of retinitis pigmentosa with membrane frizzled-related protein defects. Mol Ther. 2014;22(9):1688-1697. doi:10.1038/mt.2014.100.
  • Yoshida T, Ozawa Y, Suzuki K, Yuki K, Ohyama M, Akamatsu W et al. The use of induced pluripotent stem cells to reveal pathogenic gene mutations and explore treatments for retinitis pigmentosa. Mol Brain. 2014;7:45. doi: 10.1186/1756-6606-7-45.
  • Tran BK, Wolfensberger TJ. Retina-Implant Interaction after 16 Months Follow-up in a Patient with an Argus II Prosthesis. Klin Monbl Augenheilkd. 2017;234(4):538-540. doi: 10.1055/s-0042-121660.
  • Arslan U, Özmert E, Demirel S, Örnek F, Şermet F. Effects of subtenon-injected autologous platelet-rich plasma on visual functions in eyes with retinitis pigmentosa: preliminary clinical results. Graefes Arch Clin Exp Ophthalmol. 2018;256(5):893-908. doi: 10.1007/s00417-018-3953-5.
  • Kahraman NS, Oner A. Subtenon Injection of Autologous Platelet-Rich Plasma in Retinitis Pigmentosa: Is It a New Therapeutic Option? Open Journal of Ophthalmology. 2020;10(01):77-88. doi:10.4236/ojoph.2020.101010.
  • Seo JH, Yu HG, Lee BJ. Assessment of functional vision score and vision-specific quality of life in individuals with retinitis pigmentosa. Korean J Ophthalmol. 2009 Sep;23(3):164-168. doi:10.3341/kjo.2009.23.3.164.
  • Levinson JD, Joseph E, Ward LA, Nocera JR, Pardue MT, Bruce BB et al. Physical Activity and Quality of Life in Retinitis Pigmentosa. J Ophthalmol. 2017;2017:6950642. doi: 10.1155/2017/6950642.
  • Choi SU, Chun YS, Lee JK, Kim JT, Jeong JH, Moon NJ. Comparison of vision-related quality of life and mental health between congenital and acquired low-vision patients. Eye (Lond). 2019;33(10):1540-1546. doi: 10.1038/s41433-019-0439-6.
  • Sugawara T, Hagiwara A, Hiramatsu A, Ogata K, Mitamura Y, Yamamoto S. Relationship between peripheral visual field loss and vision-related quality of life in patients with retinitis pigmentosa. Eye (Lond). 2010;24(4):535-539. doi: 10.1038/eye.2009.176.
  • Hahm BJ, Shin YW, Shim EJ, Jeon HJ, Seo JM, Chung H et al. Depression and the vision-related quality of life in patients with retinitis pigmentosa. Br J Ophthalmol. 2008;92(5):650-654. doi: 10.1136/bjo.2007.127092.
  • Chaumet-Riffaud AE, Chaumet-Riffaud P, Cariou A, Devisme C, Audo I, Sahel JA et al. Impact of Retinitis Pigmentosa on Quality of Life, Mental Health, and Employment Among Young Adults. Am J Ophthalmol. 2017;177:169-174. doi: 10.1016/j.ajo.2017.02.016.
  • Campochiaro PA, Mir TA. The mechanism of cone cell death in Retinitis Pigmentosa. Prog Retin Eye Res. 2018;62:24-37. doi: 10.1016/j.preteyeres.2017.08.004.
  • Newton F, Megaw R. Mechanisms of Photoreceptor Death in Retinitis Pigmentosa. Genes (Basel). 2020 Sep 24;11(10):1120. doi:10.3390/genes11101120.
  • Wang W, Lee SJ, Scott PA, Lu X, Emery D, Liu Y et al. Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa. Cell Rep.2016;15(2):372-385. doi:10.1016/j.celrep.2016.03.022.
  • Wong F, Kwok SY. The Survival of Cone Photoreceptors in Retinitis Pigmentosa. JAMA Ophthalmol. 2016;134(3):249-250. doi: 10.1001/jamaophthalmol.2015.5490.
  • Lee JH, Kim MJ, Ha SW, Kim HK. Autologous Platelet-rich Plasma Eye Drops in the Treatment of Recurrent Corneal Erosions. Korean J Ophthalmol. 2016;30(2):101-107. doi:10.3341/kjo.2016.30.2.101.
  • Anitua E, Muruzabal F, de la Fuente M, Merayo J, Durán J, Orive G. Plasma Rich in Growth Factors for the Treatment of Ocular Surface Diseases. Curr Eye Res. 2016;41(7):875-882. doi:10.3109/02713683.2015.1104362.
  • Di Pierdomenico J, Scholz R, Valiente-Soriano FJ, Sánchez-Migallón MC, Vidal-Sanz M, Langmann T et al. Neuroprotective Effects of FGF2 and Minocycline in Two Animal Models of Inherited Retinal Degeneration. Invest Ophthalmol Vis Sci. 2018;59(11):4392-4403. doi:10.1167/iovs.18-24621.
  • Toprak AB, Eser E, Güler C, Baser FE, Mayali H. Cross-validation of the Turkish Version of the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ 25),Ophthalmic Epidemiol. 2005;12(4):259-269. doi: 10.1080/09286580590967763.
  • Sahli E, Arslan U, Özmert E, İdil A. Evaluation of the effect of subtenon autologous platelet-rich plasma injections on visual functions in patients with retinitis pigmentosa. Regen Med. 2021;16(2):131-143. doi: 10.2217/rme-2020-0075.
  • Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int J Mol Sci.2020;21(20):7794. doi:10.3390/ijms21207794.
  • Sahel JA, Léveillard T, Picaud S, Dalkara D, Marazova K, Safran A et al. Functional rescue of cone photoreceptors in retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol. 2013;251(7):1669-1677. doi: 10.1007/s00417-013-2314-7.
  • Koenekoop RK. Why some photoreceptors die, while others remain dormant: lessons from RPE65 and LRAT associated retinal dystrophies. Ophthalmic Genet.2011;32(2):126-128. doi:10.3109/13816810.2010.544361.
  • Amable PR, Carias RB, Teixeira MV, da Cruz Pacheco I, Corrêa do Amaral RJ, Granjeiro JM et al. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. 2013;4(3):67. doi: 10.1186/scrt218.
  • Hersant B, Sid-Ahmed M, Braud L, Jourdan M, Baba-Amer Y, Meningaud JP et al. Platelet-Rich Plasma Improves the Wound Healing Potential of Mesenchymal Stem Cells through Paracrine and Metabolism Alterations. Stem Cells Int. 2019;2019:1234263. doi:10.1155/2019/1234263.
  • Mangione CM, Lee PP, Pitts J, Gutierrez P, Berry S, Hays RD. Psychometric properties of the National Eye Institute Visual Function Questionnaire (NEI-VFQ). NEI-VFQ Field Test Investigators. Arch Ophthalmol. 1998;116(11):1496-1504. doi:10.1001/archopht.116.11.1496.
  • Sugawara T, Sato E, Baba T, Hagiwara A, Tawada A, Yamamoto S. Relationship between vision-related quality of life and microperimetry-determined macular sensitivity in patients with retinitis pigmentosa. Jpn J Ophthalmol. 2011;55(6):643-646. doi: 10.1007/s10384-011-0080-9.
  • Markowitz SN. Principles Of Modern Low Vision Rehabilitation. Can J Ophthalmol. 2006;41(3): 289-312. doi: 10.1139/I06-027.
  • Giacomelli G, Virgili G, Giansanti F, Sato G, Cappello E, Cruciani F et al. Clinical and microperimetric predictors of reading speed in low vision patients: a structural equation modeling approach. Invest Ophthalmol Vis Sci. 2013;54 (6):4403–4408. doi: 10.1167/iovs.12-10734.
There are 31 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Articles
Authors

Deniz Altınbay 0000-0002-3976-4361

İbrahim Taşkın This is me 0000-0002-4479-0396

Publication Date April 30, 2022
Submission Date July 9, 2021
Acceptance Date August 26, 2021
Published in Issue Year 2022 Volume: 15 Issue: 1

Cite

APA Altınbay, D., & Taşkın, İ. (2022). Retinitis pigmentozalı hastalarda trombositten zengin plazma enjeksiyon uygulamaları. Mersin Üniversitesi Sağlık Bilimleri Dergisi, 15(1), 29-37. https://doi.org/10.26559/mersinsbd.967974
AMA Altınbay D, Taşkın İ. Retinitis pigmentozalı hastalarda trombositten zengin plazma enjeksiyon uygulamaları. Mersin Univ Saglık Bilim derg. April 2022;15(1):29-37. doi:10.26559/mersinsbd.967974
Chicago Altınbay, Deniz, and İbrahim Taşkın. “Retinitis Pigmentozalı Hastalarda Trombositten Zengin Plazma Enjeksiyon Uygulamaları”. Mersin Üniversitesi Sağlık Bilimleri Dergisi 15, no. 1 (April 2022): 29-37. https://doi.org/10.26559/mersinsbd.967974.
EndNote Altınbay D, Taşkın İ (April 1, 2022) Retinitis pigmentozalı hastalarda trombositten zengin plazma enjeksiyon uygulamaları. Mersin Üniversitesi Sağlık Bilimleri Dergisi 15 1 29–37.
IEEE D. Altınbay and İ. Taşkın, “Retinitis pigmentozalı hastalarda trombositten zengin plazma enjeksiyon uygulamaları”, Mersin Univ Saglık Bilim derg, vol. 15, no. 1, pp. 29–37, 2022, doi: 10.26559/mersinsbd.967974.
ISNAD Altınbay, Deniz - Taşkın, İbrahim. “Retinitis Pigmentozalı Hastalarda Trombositten Zengin Plazma Enjeksiyon Uygulamaları”. Mersin Üniversitesi Sağlık Bilimleri Dergisi 15/1 (April 2022), 29-37. https://doi.org/10.26559/mersinsbd.967974.
JAMA Altınbay D, Taşkın İ. Retinitis pigmentozalı hastalarda trombositten zengin plazma enjeksiyon uygulamaları. Mersin Univ Saglık Bilim derg. 2022;15:29–37.
MLA Altınbay, Deniz and İbrahim Taşkın. “Retinitis Pigmentozalı Hastalarda Trombositten Zengin Plazma Enjeksiyon Uygulamaları”. Mersin Üniversitesi Sağlık Bilimleri Dergisi, vol. 15, no. 1, 2022, pp. 29-37, doi:10.26559/mersinsbd.967974.
Vancouver Altınbay D, Taşkın İ. Retinitis pigmentozalı hastalarda trombositten zengin plazma enjeksiyon uygulamaları. Mersin Univ Saglık Bilim derg. 2022;15(1):29-37.

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