Integrated Assessment of OCT, Multimodal Imaging, and Cytokine Markers for Predicting Treatment Responses in Retinal Vein Occlusion Associated Macular Edema: A Comparative Review of Anti-VEGF and Steroid Therapies
Abstract
:1. Introduction
Treatment | Studies | Methods | Results |
---|---|---|---|
Laser Therapy: | |||
Focal laser photocoagulation | BVOS (1984) [8] | BRVO ME patients with VA ≤ 20/40: grid pattern laser vs. observation | - VA gain in ≥ 2 lines in 65% vs. 37% of untreated - no VA gain for CRVO (CVOS study) |
Anti-VEGF agents: | |||
- Ranibizumab | BRAVO [16] (BRVO) CRUISE [16] (CRVO) | 0.3 mg vs. 0.5 mg vs. sham 0.3 mg vs. 0.5 mg vs. sham | at 6 months: +16.6 vs. +18.3 vs. +7.3 significant letter gain at 6 months: +12.7 vs. +14.9 vs. +0.8 significant letter gain |
- Aflibercept | VIBRANT [12] (BRVO) COPERNICUS [18] (CRVO) GALILEO [19] (CRVO) | 2.0 mg vs. grid laser 2.0 mg vs. sham 2.0 mg vs. sham | at week 24: +17.0 vs. +6.9 significant letter gain at week 24: +17.3 vs. −4.0 significant letter gain at week 52: +16.9 vs. +3.8 significant letter gain |
- Faricimab | BALATON [17] (BRVO) COMINO [17] (CRVO) | 6.0 mg vs. 2.0 mg aflibercept 6.0 mg vs. 2.0 mg aflibercept | at week 24: +16.9 vs. +17.5 noninferior letter change at week 24: +16.9 vs. +17.3 noninferior letter change |
- Bevacizumab | Off-label use | ||
Steroids | |||
- TA | SCORE [37] | 1 mg vs. 4 mg vs. standard of care (grid laser/observation) | at 12 months: for BRVO (grid laser) +5.7 vs. +4.0 vs. +4.2 no significant letter gain for CRVO (observation) −1.2 vs. −1.2 vs. −12.1 signifcant letter change higher cataract formation and IOP in TA groups (4 mg > 1 mg) |
- DEX | GENEVA [38] | 0.7 mg vs. 0.35 mg vs. sham | - time to ≥15-letter gain shorter in DEX implant groups vs. sham (p < 0.001) - no significant difference in cataract incidence or IOP increase by day 180 |
2. Method
3. Results
3.1. Inflammation as a Crucial Pathomechanism of ME in RVO
3.2. Cytokines Involved in RVO and RVO-Associated ME
3.2.1. Interleukin (IL)-6
3.2.2. Interleukin (IL)-8
3.2.3. Interleukin-12 (IL-12) and Interleukin-13 (IL-13)
3.3. Growth Factors
3.3.1. Vascular Endothelial Growth Factor (VEGF)
3.3.2. Platelet-Derived Growth Factor (PDGF)
3.3.3. Monocyte Chemoattractant Protein (MCP-1)
3.3.4. Intercellular Adhesion Molecule 1 (ICAM-1)
3.3.5. Interferon-Inducible 10-kDa Protein (IP-10)
3.3.6. Pentraxin 3 (PTX 3)
3.3.7. Erythropoetin (EPO)
3.3.8. Angiopoietin-2 (ANG2)
3.4. Imaging Biomarkers in RVO-Associated ME
3.4.1. Cardinal Features in Spectral Domain (SD) Optical Coherence Tomography (OCT)
3.4.2. Features in Optical Coherence Tomography (OCT)–Angiography (OCT-A)
3.4.3. Features on Fluorescein Angiography (FA)
3.4.4. Aqueous Flare
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Song, P.; Xu, Y.; Zha, M.; Zhang, Y.; Rudan, I. Global epidemiology of retinal vein occlusion: A systematic review and meta-analysis of prevalence, incidence, and risk factors. J. Glob. Health 2019, 9, 010427. [Google Scholar] [CrossRef] [PubMed]
- Ramin, S.; Rostami, F.; Ahmadieh, H.; Daftarian, N.; Nourinia, R.; Abbasi, A.; Kheiri, B.; Sabbaghi, H.; Sheibani, K. Vision-related quality of life in patients with retinal vein occlusion. Int. Ophthalmol. 2024, 44, 114. [Google Scholar] [CrossRef] [PubMed]
- McIntosh, R.L.; Rogers, S.L.; Lim, L.; Cheung, N.; Wang, J.J.; Mitchell, P.; Kowalski, J.W.; Nguyen, H.P.; Wong, T.Y. Natural history of central retinal vein occlusion: An evidence-based systematic review. Ophthalmology 2010, 117, 1113–1123.e15. [Google Scholar] [CrossRef]
- Rogers, S.L.; McIntosh, R.L.; Lim, L.; Mitchell, P.; Cheung, N.; Kowalski, J.W.; Nguyen, H.P.; Wang, J.J.; Wong, T.Y. Natural history of branch retinal vein occlusion: An evidence-based systematic review. Ophthalmology 2010, 117, 1094–1101.e1095. [Google Scholar] [CrossRef]
- Zhang, M.; Liu, Y.; Song, M.; Yu, Y.; Ruan, S.; Zheng, K.; Wang, F.; Sun, X. Intravitreal Dexamethasone Implant Has Better Retinal Perfusion than Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema Secondary to Retinal Vein Occlusion: A Five-Year Real-World Study. Ophthalmic Res. 2023, 66, 247–258. [Google Scholar] [CrossRef]
- Gale, R.; Gill, C.; Pikoula, M.; Lee, A.Y.; Hanson, R.L.W.; Denaxas, S.; Egan, C.; Tufail, A.; Taylor, P.; Group, U.E.D.U. Multicentre study of 4626 patients assesses the effectiveness, safety and burden of two categories of treatments for central retinal vein occlusion: Intravitreal anti-vascular endothelial growth factor injections and intravitreal Ozurdex injections. Br. J. Ophthalmol. 2021, 105, 1571–1576. [Google Scholar] [CrossRef] [PubMed]
- Hayreh, S.S. Ocular vascular occlusive disorders: Natural history of visual outcome. Prog. Retin. Eye Res. 2014, 41, 1–25. [Google Scholar] [CrossRef]
- Argon laser photocoagulation for macular edema in branch vein occlusion. The Branch Vein Occlusion Study Group. Am. J. Ophthalmol. 1984, 98, 271–282. [CrossRef]
- Koss, M.J.; Pfister, M.; Rothweiler, F.; Michaelis, M.; Cinatl, J.; Schubert, R.; Koch, F.H. Comparison of cytokine levels from undiluted vitreous of untreated patients with retinal vein occlusion. Acta Ophthalmol. 2012, 90, e98–e103. [Google Scholar] [CrossRef]
- Green, W.R.; Chan, C.C.; Hutchins, G.M.; Terry, J.M. Central retinal vein occlusion: A prospective histopathologic study of 29 eyes in 28 cases. Trans. Am. Ophthalmol. Soc. 1981, 79, 371–422. [Google Scholar] [CrossRef]
- Baseline and early natural history report. The Central Vein Occlusion Study. Arch. Ophthalmol. 1993, 111, 1087–1095. [CrossRef] [PubMed]
- Campochiaro, P.A.; Clark, W.L.; Boyer, D.S.; Heier, J.S.; Brown, D.M.; Vitti, R.; Kazmi, H.; Berliner, A.J.; Erickson, K.; Chu, K.W.; et al. Intravitreal aflibercept for macular edema following branch retinal vein occlusion: The 24-week results of the VIBRANT study. Ophthalmology 2015, 122, 538–544. [Google Scholar] [CrossRef] [PubMed]
- Campa, C.; Alivernini, G.; Bolletta, E.; Parodi, M.B.; Perri, P. Anti-VEGF Therapy for Retinal Vein Occlusions. Curr. Drug Targets 2016, 17, 328–336. [Google Scholar] [CrossRef]
- Iliev, M.E.; Domig, D.; Wolf-Schnurrbursch, U.; Wolf, S.; Sarra, G.M. Intravitreal bevacizumab (Avastin) in the treatment of neovascular glaucoma. Am. J. Ophthalmol. 2006, 142, 1054–1056. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Paulus, Y.M.; Shuai, Y.; Fang, W.; Liu, Q.; Yuan, S. New Developments in the Classification, Pathogenesis, Risk Factors, Natural History, and Treatment of Branch Retinal Vein Occlusion. J. Ophthalmol. 2017, 2017, 4936924. [Google Scholar] [CrossRef]
- Campochiaro, P.A.; Heier, J.S.; Feiner, L.; Gray, S.; Saroj, N.; Rundle, A.C.; Murahashi, W.Y.; Rubio, R.G.; Investigators, B. Ranibizumab for macular edema following branch retinal vein occlusion: Six-month primary end point results of a phase III study. Ophthalmology 2010, 117, 1102–1112.e1. [Google Scholar] [CrossRef]
- Hattenbach, L.O.; Abreu, F.; Arrisi, P.; Basu, K.; Danzig, C.J.; Guymer, R.; Haskova, Z.; Heier, J.S.; Kotecha, A.; Liu, Y.; et al. BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale. Ophthalmol. Sci. 2023, 3, 100302. [Google Scholar] [CrossRef]
- Brown, D.M.; Heier, J.S.; Clark, W.L.; Boyer, D.S.; Vitti, R.; Berliner, A.J.; Zeitz, O.; Sandbrink, R.; Zhu, X.; Haller, J.A. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am. J. Ophthalmol. 2013, 155, 429–437.e427. [Google Scholar] [CrossRef]
- Korobelnik, J.F.; Holz, F.G.; Roider, J.; Ogura, Y.; Simader, C.; Schmidt-Erfurth, U.; Lorenz, K.; Honda, M.; Vitti, R.; Berliner, A.J.; et al. Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study. Ophthalmology 2014, 121, 202–208. [Google Scholar] [CrossRef]
- Tadayoni, R.; Waldstein, S.M.; Boscia, F.; Gerding, H.; Gekkieva, M.; Barnes, E.; Das Gupta, A.; Wenzel, A.; Pearce, I.; Group, B.S. Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study. Ophthalmology 2017, 124, 1778–1787. [Google Scholar] [CrossRef]
- Campochiaro, P.A.; Sophie, R.; Pearlman, J.; Brown, D.M.; Boyer, D.S.; Heier, J.S.; Marcus, D.M.; Feiner, L.; Patel, A.; Group, R.S. Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: The RETAIN study. Ophthalmology 2014, 121, 209–219. [Google Scholar] [CrossRef]
- Menke, M.N.; Ebneter, A.; Zinkernagel, M.S.; Wolf, S. Differentiation between Good and Low-Responders to Intravitreal Ranibizumab for Macular Edema Secondary to Retinal Vein Occlusion. J. Ophthalmol. 2016, 2016, 9875741. [Google Scholar] [CrossRef]
- Noma, H.; Mimura, T.; Shimada, K. Role of inflammation in previously untreated macular edema with branch retinal vein occlusion. BMC Ophthalmol. 2014, 14, 67. [Google Scholar] [CrossRef] [PubMed]
- Noma, H.; Yasuda, K.; Shimura, M. Cytokines and Pathogenesis of Central Retinal Vein Occlusion. J. Clin. Med. 2020, 9, 3457. [Google Scholar] [CrossRef] [PubMed]
- Noma, H.; Funatsu, H.; Mimura, T.; Harino, S.; Hori, S. Vitreous levels of interleukin-6 and vascular endothelial growth factor in macular edema with central retinal vein occlusion. Ophthalmology 2009, 116, 87–93. [Google Scholar] [CrossRef] [PubMed]
- Wang, B.; Zhang, X.; Chen, H.; Koh, A.; Zhao, C.; Chen, Y. A Review of Intraocular Biomolecules in Retinal Vein Occlusion: Toward Potential Biomarkers for Companion Diagnostics. Front. Pharmacol. 2022, 13, 859951. [Google Scholar] [CrossRef] [PubMed]
- Matsushima, R.; Noma, H.; Yasuda, K.; Goto, H.; Shimura, M. Role of Cytokines in Ranibizumab Therapy for Macular Edema in Patients with Central Retinal Vein Occlusion. J. Ocul. Pharmacol. Ther. 2019, 35, 407–412. [Google Scholar] [CrossRef]
- Karia, N. Retinal vein occlusion: Pathophysiology and treatment options. Clin. Ophthalmol. 2010, 4, 809–816. [Google Scholar] [CrossRef]
- Kent, D.; Vinores, S.A.; Campochiaro, P.A. Macular oedema: The role of soluble mediators. Br. J. Ophthalmol. 2000, 84, 542–545. [Google Scholar] [CrossRef]
- Campochiaro, P.A.; Hafiz, G.; Mir, T.A.; Scott, A.W.; Sophie, R.; Shah, S.M.; Ying, H.S.; Lu, L.; Chen, C.; Campbell, J.P.; et al. Pro-Permeability Factors After Dexamethasone Implant in Retinal Vein Occlusion; the Ozurdex for Retinal Vein Occlusion (ORVO) Study. Am. J. Ophthalmol. 2015, 160, 313–321.e19. [Google Scholar] [CrossRef]
- Distler, C.; Dreher, Z. Glia cells of the monkey retina--II. Müller cells. Vis. Res. 1996, 36, 2381–2394. [Google Scholar] [CrossRef] [PubMed]
- Reichenbach, A.; Bringmann, A. Glia of the human retina. Glia 2020, 68, 768–796. [Google Scholar] [CrossRef]
- Köferl, P.; Hollborn, M.; Rehak, J.; Iandiev, I.; Dukic-Stefanovic, S.; Wiedemann, P.; Kohen, L.; Bringmann, A.; Rehak, M. Effects of arteriolar constriction on retinal gene expression and Müller cell responses in a rat model of branch retinal vein occlusion. Graefes Arch. Clin. Exp. Ophthalmol. 2014, 252, 257–265. [Google Scholar] [CrossRef] [PubMed]
- Bek, T. Capillary closure secondary to retinal vein occlusion. A morphological, histopathological, and immunohistochemical study. Acta Ophthalmol. Scand. 1998, 76, 643–648. [Google Scholar] [CrossRef] [PubMed]
- Xin, X.; Rodrigues, M.; Umapathi, M.; Kashiwabuchi, F.; Ma, T.; Babapoor-Farrokhran, S.; Wang, S.; Hu, J.; Bhutto, I.; Welsbie, D.S.; et al. Hypoxic retinal Muller cells promote vascular permeability by HIF-1-dependent up-regulation of angiopoietin-like 4. Proc. Natl. Acad. Sci. USA 2013, 110, E3425–E3434. [Google Scholar] [CrossRef] [PubMed]
- Schmidt-Erfurth, U.; Garcia-Arumi, J.; Gerendas, B.S.; Midena, E.; Sivaprasad, S.; Tadayoni, R.; Wolf, S.; Loewenstein, A. Guidelines for the Management of Retinal Vein Occlusion by the European Society of Retina Specialists (EURETINA). Ophthalmologica 2019, 242, 123–162. [Google Scholar] [CrossRef] [PubMed]
- Scott, I.U.; Ip, M.S.; VanVeldhuisen, P.C.; Oden, N.L.; Blodi, B.A.; Fisher, M.; Chan, C.K.; Gonzalez, V.H.; Singerman, L.J.; Tolentino, M.; et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular Edema secondary to branch retinal vein occlusion: The Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6. Arch. Ophthalmol. 2009, 127, 1115–1128. [Google Scholar] [CrossRef]
- Haller, J.A.; Bandello, F.; Belfort, R., Jr.; Blumenkranz, M.S.; Gillies, M.; Heier, J.; Loewenstein, A.; Yoon, Y.H.; Jacques, M.L.; Jiao, J.; et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010, 117, 1134–1146.e3. [Google Scholar] [CrossRef]
- Li, X.; Wang, N.; Liang, X.; Xu, G.; Li, X.Y.; Jiao, J.; Lou, J.; Hashad, Y. Safety and efficacy of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusion in Chinese patients: Randomized, sham-controlled, multicenter study. Graefes Arch. Clin. Exp. Ophthalmol. 2018, 256, 59–69. [Google Scholar] [CrossRef]
- Hattenbach, L.O.; Feltgen, N.; Bertelmann, T.; Schmitz-Valckenberg, S.; Berk, H.; Eter, N.; Lang, G.E.; Rehak, M.; Taylor, S.R.; Wolf, A.; et al. Head-to-head comparison of ranibizumab PRN versus single-dose dexamethasone for branch retinal vein occlusion (COMRADE-B). Acta Ophthalmol. 2018, 96, e10–e18. [Google Scholar] [CrossRef]
- Hoerauf, H.; Feltgen, N.; Weiss, C.; Paulus, E.M.; Schmitz-Valckenberg, S.; Pielen, A.; Puri, P.; Berk, H.; Eter, N.; Wiedemann, P.; et al. Clinical Efficacy and Safety of Ranibizumab Versus Dexamethasone for Central Retinal Vein Occlusion (COMRADE C): A European Label Study. Am. J. Ophthalmol. 2016, 169, 258–267. [Google Scholar] [CrossRef] [PubMed]
- Chatziralli, I.; Theodossiadis, G.; Kabanarou, S.A.; Theodossiadis, P. Ranibizumab versus dexamethasone implant for central retinal vein occlusion: Special remarks of the RANIDEX study. Graefes Arch. Clin. Exp. Ophthalmol. 2017, 255, 2077–2078. [Google Scholar] [CrossRef]
- Gu, X.; Yu, X.; Song, S.; Dai, H. Intravitreal Dexamethasone Implant versus Intravitreal Ranibizumab for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion in a Chinese Population. Ophthalmic Res. 2017, 58, 8–14. [Google Scholar] [CrossRef]
- Ozkok, A.; Saleh, O.A.; Sigford, D.K.; Heroman, J.W.; Schaal, S. THE OMAR STUDY: Comparison of Ozurdex and Triamcinolone Acetonide for Refractory Cystoid Macular Edema in Retinal Vein Occlusion. Retina 2015, 35, 1393–1400. [Google Scholar] [CrossRef] [PubMed]
- Eibenberger, K.; Schmetterer, L.; Rezar-Dreindl, S.; Wozniak, P.; Told, R.; Mylonas, G.; Krall, C.; Schmidt-Erfurth, U.; Sacu, S. Effects of Intravitreal Dexamethasone Implants on Retinal Oxygen Saturation, Vessel Diameter, and Retrobulbar Blood Flow Velocity in ME Secondary to RVO. Investig. Ophthalmol. Vis. Sci. 2017, 58, 5022–5029. [Google Scholar] [CrossRef]
- Chen, Y.; Xia, Q.; Zeng, Y.; Zhang, Y.; Zhang, M. Regulations of Retinal Inflammation: Focusing on Müller Glia. Front. Cell Dev. Biol. 2022, 10, 898652. [Google Scholar] [CrossRef]
- Noma, H.; Mimura, T.; Tatsugawa, M.; Shimada, K. Aqueous flare and inflammatory factors in macular edema with central retinal vein occlusion: A case series. BMC Ophthalmol. 2013, 13, 78. [Google Scholar] [CrossRef]
- Funk, M.; Kriechbaum, K.; Prager, F.; Benesch, T.; Georgopoulos, M.; Zlabinger, G.J.; Schmidt-Erfurth, U. Intraocular concentrations of growth factors and cytokines in retinal vein occlusion and the effect of therapy with bevacizumab. Investig. Ophthalmol. Vis. Sci. 2009, 50, 1025–1032. [Google Scholar] [CrossRef] [PubMed]
- Noma, H.; Funatsu, H.; Harino, S.; Mimura, T.; Eguchi, S.; Hori, S. Vitreous inflammatory factors in macular edema with central retinal vein occlusion. Jpn. J. Ophthalmol. 2011, 55, 248–255. [Google Scholar] [CrossRef]
- Noma, H.; Mimura, T.; Masahara, H.; Shimada, K. Pentraxin 3 and other inflammatory factors in central retinal vein occlusion and macular edema. Retina 2014, 34, 352–359. [Google Scholar] [CrossRef]
- Suzuki, Y.; Nakazawa, M.; Suzuki, K.; Yamazaki, H.; Miyagawa, Y. Expression profiles of cytokines and chemokines in vitreous fluid in diabetic retinopathy and central retinal vein occlusion. Jpn. J. Ophthalmol. 2011, 55, 256–263. [Google Scholar] [CrossRef] [PubMed]
- Rezar-Dreindl, S.; Eibenberger, K.; Pollreisz, A.; Buhl, W.; Georgopoulos, M.; Krall, C.; Dunavolgyi, R.; Weigert, G.; Kroh, M.E.; Schmidt-Erfurth, U.; et al. Effect of intravitreal dexamethasone implant on intra-ocular cytokines and chemokines in eyes with retinal vein occlusion. Acta Ophthalmol. 2017, 95, e119–e127. [Google Scholar] [CrossRef]
- Jung, S.H.; Kim, K.A.; Sohn, S.W.; Yang, S.J. Association of aqueous humor cytokines with the development of retinal ischemia and recurrent macular edema in retinal vein occlusion. Investig. Ophthalmol. Vis. Sci. 2014, 55, 2290–2296. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, T.; Narazaki, M.; Kishimoto, T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol. 2014, 6, a016295. [Google Scholar] [CrossRef] [PubMed]
- Echevarria, F.D.; Rickman, A.E.; Sappington, R.M. Interleukin-6: A Constitutive Modulator of Glycoprotein 130, Neuroinflammatory and Cell Survival Signaling in Retina. J. Clin. Cell Immunol. 2016, 7, 439. [Google Scholar] [CrossRef]
- Pearlstein, D.P.; Ali, M.H.; Mungai, P.T.; Hynes, K.L.; Gewertz, B.L.; Schumacker, P.T. Role of mitochondrial oxidant generation in endothelial cell responses to hypoxia. Arterioscler. Thromb. Vasc. Biol. 2002, 22, 566–573. [Google Scholar] [CrossRef] [PubMed]
- Kaneda, S.; Miyazaki, D.; Sasaki, S.; Yakura, K.; Terasaka, Y.; Miyake, K.; Ikeda, Y.; Funakoshi, T.; Baba, T.; Yamasaki, A.; et al. Multivariate analyses of inflammatory cytokines in eyes with branch retinal vein occlusion: Relationships to bevacizumab treatment. Investig. Ophthalmol. Vis. Sci. 2011, 52, 2982–2988. [Google Scholar] [CrossRef]
- Mashima, A.; Noma, H.; Yasuda, K.; Goto, H.; Shimura, M. Anti-vascular endothelial growth factor agent reduces inflammation in macular edema with central retinal vein occlusion. J. Inflamm. 2019, 16, 9. [Google Scholar] [CrossRef]
- Yong, H.; Qi, H.; Yan, H.; Wu, Q.; Zuo, L. The correlation between cytokine levels in the aqueous humor and the prognostic value of anti-vascular endothelial growth factor therapy for treating macular edema resulting from retinal vein occlusion. Graefes Arch. Clin. Exp. Ophthalmol. 2021, 259, 3243–3250. [Google Scholar] [CrossRef]
- Shono, T.; Ono, M.; Izumi, H.; Jimi, S.I.; Matsushima, K.; Okamoto, T.; Kohno, K.; Kuwano, M. Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. Mol. Cell Biol. 1996, 16, 4231–4239. [Google Scholar] [CrossRef]
- Taub, D.D.; Anver, M.; Oppenheim, J.J.; Longo, D.L.; Murphy, W.J. T lymphocyte recruitment by interleukin-8 (IL-8). IL-8-induced degranulation of neutrophils releases potent chemoattractants for human T lymphocytes both in vitro and in vivo. J. Clin. Investig. 1996, 97, 1931–1941. [Google Scholar] [CrossRef] [PubMed]
- Flaxel, C.J.; Adelman, R.A.; Bailey, S.T.; Fawzi, A.; Lim, J.I.; Vemulakonda, G.A.; Ying, G.S. Retinal Vein Occlusions Preferred Practice Pattern(R). Ophthalmology 2020, 127, P288–P320. [Google Scholar] [CrossRef]
- Hao, Q.; Wang, L.; Tang, H. Vascular endothelial growth factor induces protein kinase D-dependent production of proinflammatory cytokines in endothelial cells. Am. J. Physiol. Cell Physiol. 2009, 296, C821–C827. [Google Scholar] [CrossRef] [PubMed]
- Noma, H.; Yasuda, K.; Shimura, M. Change of cytokines after intravitreal ranibizumab in patients with recurrent branch retinal vein occlusion and macular edema. Eur. J. Ophthalmol. 2021, 31, 204–210. [Google Scholar] [CrossRef] [PubMed]
- Shchuko, A.G.; Zlobin, I.V.; Iureva, T.N.; Ostanin, A.A.; Chernykh, E.R.; Mikhalevich, I.M. Intraocular cytokines in retinal vein occlusion and its relation to the efficiency of anti-vascular endothelial growth factor therapy. Indian J. Ophthalmol. 2015, 63, 905–911. [Google Scholar] [CrossRef] [PubMed]
- Noma, H.; Mimura, T.; Yasuda, K.; Shimura, M. Cytokine Kinetics after Monthly Intravitreal Bevacizumab for Retinal Vein Occlusion Associated with Macular Oedema. Ophthalmic Res. 2016, 56, 207–214. [Google Scholar] [CrossRef]
- Okunuki, Y.; Usui, Y.; Katai, N.; Kezuka, T.; Takeuchi, M.; Goto, H.; Wakabayashi, Y. Relation of intraocular concentrations of inflammatory factors and improvement of macular edema after vitrectomy in branch retinal vein occlusion. Am. J. Ophthalmol. 2011, 151, 610–616.e1. [Google Scholar] [CrossRef]
- Li, M.; Li, J.; Chen, K.; Wang, J.; Sheng, M.; Li, B. Association between Inflammatory Factors in the Aqueous Humor and Hyperreflective Foci in Patients with Intractable Macular Edema Treated with Antivascular Endothelial Growth Factor. Dis. Markers 2021, 2021, 5552824. [Google Scholar] [CrossRef]
- Noma, H.; Mimura, T.; Yasuda, K.; Shimura, M. Role of soluble vascular endothelial growth factor receptors-1 and -2, their ligands, and other factors in branch retinal vein occlusion with macular edema. Investig. Ophthalmol. Vis. Sci. 2014, 55, 3878–3885. [Google Scholar] [CrossRef]
- Noma, H.; Funatsu, H.; Mimura, T.; Eguchi, S.; Shimada, K. Role of soluble vascular endothelial growth factor receptor-2 in macular oedema with central retinal vein occlusion. Br. J. Ophthalmol. 2011, 95, 788–792. [Google Scholar] [CrossRef]
- Noma, H.; Mimura, T.; Yasuda, K.; Shimura, M. Functional-morphological parameters, aqueous flare and cytokines in macular oedema with branch retinal vein occlusion after ranibizumab. Br. J. Ophthalmol. 2017, 101, 180–185. [Google Scholar] [CrossRef] [PubMed]
- Martin, G.; Conrad, D.; Cakir, B.; Schlunck, G.; Agostini, H.T. Gene expression profiling in a mouse model of retinal vein occlusion induced by laser treatment reveals a predominant inflammatory and tissue damage response. PLoS ONE 2018, 13, e0191338. [Google Scholar] [CrossRef] [PubMed]
- Noma, H.; Funatsu, H.; Mimura, T.; Tatsugawa, M.; Shimada, K.; Eguchi, S. Vitreous inflammatory factors and serous macular detachment in branch retinal vein occlusion. Retina 2012, 32, 86–91. [Google Scholar] [CrossRef]
- Miyamoto, K.; Khosrof, S.; Bursell, S.E.; Moromizato, Y.; Aiello, L.P.; Ogura, Y.; Adamis, A.P. Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability is mediated by intercellular adhesion molecule-1 (ICAM-1). Am. J. Pathol. 2000, 156, 1733–1739. [Google Scholar] [CrossRef]
- Noma, H.; Funatsu, H.; Yamasaki, M.; Tsukamoto, H.; Mimura, T.; Sone, T.; Jian, K.; Sakamoto, I.; Nakano, K.; Yamashita, H.; et al. Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6. Am. J. Ophthalmol. 2005, 140, 256–261. [Google Scholar] [CrossRef]
- Nitta, K.; Nishinaka, A.; Hida, Y.; Nakamura, S.; Shimazawa, M.; Hara, H. Oral and ocular administration of crocetin prevents retinal edema in a murine retinal vein occlusion model. Mol. Vis. 2019, 25, 859–868. [Google Scholar]
- Rodrigues, G.B.; Abe, R.Y.; Zangalli, C.; Sodre, S.L.; Donini, F.A.; Costa, D.C.; Leite, A.; Felix, J.P.; Torigoe, M.; Diniz-Filho, A.; et al. Neovascular glaucoma: A review. Int. J. Retin. Vitr. 2016, 2, 26. [Google Scholar] [CrossRef] [PubMed]
- Oshida, E.; Arai, K.; Sakai, M.; Chikuda, M. Study of free radicals in aqueous humor in glaucoma and cataracts: Differences in presence or absence of diabetes mellitus and neovascular glaucoma. Nippon Ganka Gakkai Zasshi 2014, 118, 759–767. [Google Scholar]
- Park, S.P.; Ahn, J.K.; Mun, G.H. Aqueous vascular endothelial growth factor levels are associated with serous macular detachment secondary to branch retinal vein occlusion. Retina 2010, 30, 281–286. [Google Scholar] [CrossRef]
- Fujikawa, M.; Sawada, O.; Miyake, T.; Kakinoki, M.; Sawada, T.; Kawamura, H.; Ohji, M. Correlation between vascular endothelial growth factor and nonperfused areas in macular edema secondary to branch retinal vein occlusion. Clin. Ophthalmol. 2013, 7, 1497–1501. [Google Scholar] [CrossRef]
- Martin, A.; Abraham, J.R.; Wykoff, C.C.; Lunasco, L.; Arepalli, S.; Srivastava, S.K.; Mugnaini, C.J.; Hu, M.; Reese, J.; Brown, D.M.; et al. Correlation of Intraocular Cytokine Expression with Quantitative Ultra-widefield Fluorescein Angiographic Features in the IMAGINE Retinal Vein Occlusion Study. Investig. Ophthalmol. Vis. Sci. 2021, 62, 2169. [Google Scholar]
- Edqvist, P.H.; Niklasson, M.; Vidal-Sanz, M.; Hallböök, F.; Forsberg-Nilsson, K. Platelet-derived growth factor over-expression in retinal progenitors results in abnormal retinal vessel formation. PLoS ONE 2012, 7, e42488. [Google Scholar] [CrossRef] [PubMed]
- Fruttiger, M.; Calver, A.R.; Richardson, W.D. Platelet-derived growth factor is constitutively secreted from neuronal cell bodies but not from axons. Curr. Biol. 2000, 10, 1283–1286. [Google Scholar] [CrossRef] [PubMed]
- Reneker, L.W.; Overbeek, P.A. Lens-specific expression of PDGF-A in transgenic mice results in retinal astrocytic hamartomas. Investig. Ophthalmol. Vis. Sci. 1996, 37, 2455–2466. [Google Scholar]
- Mudhar, H.S.; Pollock, R.A.; Wang, C.; Stiles, C.D.; Richardson, W.D. PDGF and its receptors in the developing rodent retina and optic nerve. Development 1993, 118, 539–552. [Google Scholar] [CrossRef] [PubMed]
- Lindahl, P.; Johansson, B.R.; Levéen, P.; Betsholtz, C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 1997, 277, 242–245. [Google Scholar] [CrossRef] [PubMed]
- Dong, A.; Seidel, C.; Snell, D.; Ekawardhani, S.; Ahlskog, J.K.; Baumann, M.; Shen, J.; Iwase, T.; Tian, J.; Stevens, R.; et al. Antagonism of PDGF-BB suppresses subretinal neovascularization and enhances the effects of blocking VEGF-A. Angiogenesis 2014, 17, 553–562. [Google Scholar] [CrossRef]
- Noma, H.; Mimura, T.; Yasuda, K.; Shimura, M. Role of soluble vascular endothelial growth factor receptor signaling and other factors or cytokines in central retinal vein occlusion with macular edema. Investig. Ophthalmol. Vis. Sci. 2015, 56, 1122–1128. [Google Scholar] [CrossRef]
- Klein, R.; Moss, S.E.; Meuer, S.M.; Klein, B.E. The 15-year cumulative incidence of retinal vein occlusion: The Beaver Dam Eye Study. Arch. Ophthalmol. 2008, 126, 513–518. [Google Scholar] [CrossRef]
- Horiuchi, T.; Weller, P.F. Expression of vascular endothelial growth factor by human eosinophils: Upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5. Am. J. Respir. Cell Mol. Biol. 1997, 17, 70–77. [Google Scholar] [CrossRef]
- Noma, H.; Mimura, T.; Yasuda, K.; Shimura, M. Possible Molecular Basis of Bevacizumab Therapy for Macular Edema in Branch Retinal Vein Occlusion. Retina 2016, 36, 1718–1725. [Google Scholar] [CrossRef]
- Feldman, E.D.; Weinreich, D.M.; Carroll, N.M.; Burness, M.L.; Feldman, A.L.; Turner, E.; Xu, H.; Alexander, H.R., Jr. Interferon gamma-inducible protein 10 selectively inhibits proliferation and induces apoptosis in endothelial cells. Ann. Surg. Oncol. 2006, 13, 125–133. [Google Scholar] [CrossRef]
- Bodnar, R.J.; Yates, C.C.; Wells, A. IP-10 blocks vascular endothelial growth factor-induced endothelial cell motility and tube formation via inhibition of calpain. Circ. Res. 2006, 98, 617–625. [Google Scholar] [CrossRef]
- Woo, J.M.; Kwon, M.Y.; Shin, D.Y.; Kang, Y.H.; Hwang, N.; Chung, S.W. Human retinal pigment epithelial cells express the long pentraxin PTX3. Mol. Vis. 2013, 19, 303–310. [Google Scholar]
- Park, K.S.; Kim, J.W.; An, J.H.; Woo, J.M. Elevated plasma pentraxin 3 and its association with retinal vein occlusion. Korean J. Ophthalmol. 2014, 28, 460–465. [Google Scholar] [CrossRef] [PubMed]
- Bocker-Meffert, S.; Rosenstiel, P.; Rohl, C.; Warneke, N.; Held-Feindt, J.; Sievers, J.; Lucius, R. Erythropoietin and VEGF promote neural outgrowth from retinal explants in postnatal rats. Investig. Ophthalmol. Vis. Sci. 2002, 43, 2021–2026. [Google Scholar]
- Shin, H.J.; Kim, H.C.; Moon, J.W. Aqueous levels of erythropoietin in acute retinal vein occlusion with macular edema. Int. J. Ophthalmol. 2014, 7, 501–506. [Google Scholar] [CrossRef] [PubMed]
- Hernández, C.; Simó, R. Erythropoietin produced by the retina: Its role in physiology and diabetic retinopathy. Endocrine 2012, 41, 220–226. [Google Scholar] [CrossRef] [PubMed]
- Stahl, A.; Buchwald, A.; Martin, G.; Junker, B.; Chen, J.; Hansen, L.L.; Agostini, H.T.; Smith, L.E.; Feltgen, N. Vitreal levels of erythropoietin are increased in patients with retinal vein occlusion and correlate with vitreal VEGF and the extent of macular edema. Retina 2010, 30, 1524–1529. [Google Scholar] [CrossRef]
- Regula, J.T.; Lundh von Leithner, P.; Foxton, R.; Barathi, V.A.; Chui Ming, G.C.; Tun, S.B.B.; Wey, Y.S.; Iwata, D.; Dostalek, M.; Moelleken, J.; et al. Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. EMBO Mol. Med. 2019, 11, e10666. [Google Scholar] [CrossRef]
- Lip, P.L.; Chatterjee, S.; Caine, G.J.; Hope-Ross, M.; Gibson, J.; Blann, A.D.; Lip, G.Y. Plasma vascular endothelial growth factor, angiopoietin-2, and soluble angiopoietin receptor tie-2 in diabetic retinopathy: Effects of laser photocoagulation and angiotensin receptor blockade. Br. J. Ophthalmol. 2004, 88, 1543–1546. [Google Scholar] [CrossRef] [PubMed]
- Ng, D.S.; Yip, Y.W.; Bakthavatsalam, M.; Chen, L.J.; Ng, T.K.; Lai, T.Y.; Pang, C.P.; Brelen, M.E. Elevated angiopoietin 2 in aqueous of patients with neovascular age related macular degeneration correlates with disease severity at presentation. Sci. Rep. 2017, 7, 45081. [Google Scholar] [CrossRef] [PubMed]
- Sagong, M.; Noh, D.; Lee, J.; Choi, N.; Kim, I.; Hemert, J.; Son, J.; KIM, Y.Y.; Cha, S. Difference of aqueous cytokines according to distribution of ischemia assessed by ultra-widefield fluorescein angiography in macular edema secondary to retinal vein occlusion. Investig. Ophthalmol. Vis. Sci. 2018, 59, 5432. [Google Scholar]
- Georgalas, L.; Tservakis, I.; Kiskira, E.E.; Petrou, P.; Papaconstantinou, D.; Kanakis, M. Efficacy and safety of dexamethasone intravitreal implant in patients with retinal vein occlusion resistant to anti-VEGF therapy: A 12-month prospective study. Cutan. Ocul. Toxicol. 2019, 38, 330–337. [Google Scholar] [CrossRef] [PubMed]
- Pielen, A.; Buhler, A.D.; Heinzelmann, S.U.; Bohringer, D.; Ness, T.; Junker, B. Switch of Intravitreal Therapy for Macular Edema Secondary to Retinal Vein Occlusion from Anti-VEGF to Dexamethasone Implant and Vice Versa. J. Ophthalmol. 2017, 2017, 5831682. [Google Scholar] [CrossRef]
- Yoo, J.H.; Ahn, J.; Oh, J.; Cha, J.; Kim, S.W. Risk factors of recurrence of macular oedema associated with branch retinal vein occlusion after intravitreal bevacizumab injection. Br. J. Ophthalmol. 2017, 101, 1334–1339. [Google Scholar] [CrossRef]
- Huang, P.W.; Lai, C.C.; Hwang, Y.S.; Wu, W.C.; Wu, C.H.; Huang, J.C.; Chen, Y.P.; Liu, L.; Chen, K.J.; Yeung, L. Treatment responses for branch retinal vein occlusion predicted by semi-automated fluorescein angiography quantification. BMC Ophthalmol. 2022, 22, 50. [Google Scholar] [CrossRef]
- Son, W.; Jeong, W.J.; Park, J.M.; Kim, J.Y.; Ji, Y.S.; Sagong, M. Predictors of treatment outcomes following treat-and-extend regimen with aflibercept for branch retinal vein occlusion: Post-hoc analysis of the PLATON trial. Sci. Rep. 2023, 13, 11730. [Google Scholar] [CrossRef]
- Chatziralli, I.; Kazantzis, D.; Kroupis, C.; Machairoudia, G.; Dimitriou, E.; Theodossiadis, G.; Theodossiadis, P.; Sergentanis, T.N. The impact of laboratory findings and optical coherence tomography biomarkers on response to intravitreal anti-VEGF treatment in patients with retinal vein occlusion. Int. Ophthalmol. 2022, 42, 3449–3457. [Google Scholar] [CrossRef]
- Choi, Y.J.; Jee, D.; Kwon, J.W. Characteristics of major and macular branch retinal vein occlusion. Sci. Rep. 2022, 12, 14103. [Google Scholar] [CrossRef]
- Battaglia Parodi, M.; Iacono, P.; Scaramuzzi, M.; Bandello, F. Outer Retinal Layer Changes after Dexamethasone Implant for Central Retinal Vein Occlusion. Retina 2017, 37, 1888–1895. [Google Scholar] [CrossRef] [PubMed]
- Tilgner, E.; Dalcegio Favretto, M.; Tuisl, M.; Wiedemann, P.; Rehak, M. Macular cystic changes as predictive factor for the recurrence of macular oedema in branch retinal vein occlusion. Acta Ophthalmol. 2017, 95, e592–e596. [Google Scholar] [CrossRef] [PubMed]
- Markan, A.; Agarwal, A.; Arora, A.; Bazgain, K.; Rana, V.; Gupta, V. Novel imaging biomarkers in diabetic retinopathy and diabetic macular edema. Ther. Adv. Ophthalmol. 2020, 12, 2515841420950513. [Google Scholar] [CrossRef] [PubMed]
- Ding, X.; Hu, Y.; Yu, H.; Li, Q. Changes of Optical Coherence Tomography Biomarkers in Macular Edema Secondary to Retinal Vein Occlusion After Anti-VEGF and Anti-Inflammatory Therapies. Drug Des. Dev. Ther. 2022, 16, 717–725. [Google Scholar] [CrossRef]
- Do, J.R.; Park, S.J.; Shin, J.P.; Park, D.H. Assessment of Hyperreflective Foci after Bevacizumab or Dexamethasone Treatment According to Duration of Macular Edema in Patients with Branch Retinal Vein Occlusion. Retina 2021, 41, 355–365. [Google Scholar] [CrossRef]
- Zur, D.; Iglicki, M.; Busch, C.; Invernizzi, A.; Mariussi, M.; Loewenstein, A.; International Retina, G. OCT Biomarkers as Functional Outcome Predictors in Diabetic Macular Edema Treated with Dexamethasone Implant. Ophthalmology 2018, 125, 267–275. [Google Scholar] [CrossRef]
- Kim, K.T.; Kim, D.Y.; Chae, J.B. Association between Hyperreflective Foci on Spectral-Domain Optical Coherence Tomography and Early Recurrence of Diabetic Macular Edema after Intravitreal Dexamethasone Implantation. J. Ophthalmol. 2019, 2019, 3459164. [Google Scholar] [CrossRef]
- Aljundi, W.; Gradinger, F.; Langenbucher, A.; Sideroudi, H.; Seitz, B.; Abdin, A.D. Choroidal thickness as a possible predictor of non-response to intravitreal bevacizumab for macular edema after retinal vein occlusion. Sci. Rep. 2023, 13, 451. [Google Scholar] [CrossRef]
- Castro-Navarro, V.; Monferrer-Adsuara, C.; Navarro-Palop, C.; Montero-Hernandez, J.; Cervera-Taulet, E. Optical coherence tomography biomarkers in patients with macular edema secondary to retinal vein occlusion treated with dexamethasone implant. BMC Ophthalmol. 2022, 22, 191. [Google Scholar] [CrossRef]
- Mimouni, M.; Segev, O.; Dori, D.; Geffen, N.; Flores, V.; Segal, O. Disorganization of the Retinal Inner Layers as a Predictor of Visual Acuity in Eyes With Macular Edema Secondary to Vein Occlusion. Am. J. Ophthalmol. 2017, 182, 160–167. [Google Scholar] [CrossRef]
- Babiuch, A.S.; Han, M.; Conti, F.F.; Wai, K.; Silva, F.Q.; Singh, R.P. Association of Disorganization of Retinal Inner Layers With Visual Acuity Response to Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema Secondary to Retinal Vein Occlusion. JAMA Ophthalmol. 2019, 137, 38–46. [Google Scholar] [CrossRef] [PubMed]
- Ko, J.; Kwon, O.W.; Byeon, S.H. Optical coherence tomography predicts visual outcome in acute central retinal vein occlusion. Retina 2014, 34, 1132–1141. [Google Scholar] [CrossRef]
- Banaee, T.; Singh, R.P.; Champ, K.; Conti, F.F.; Wai, K.; Bena, J.; Beven, L.; Ehlers, J.P. Ellipsoid Zone Mapping Parameters In Retinal Venous Occlusive Disease With Associated Macular Edema. Ophthalmol. Retina 2018, 2, 836–841. [Google Scholar] [CrossRef] [PubMed]
- Sasajima, H.; Zako, M.; Murotani, K.; Ishida, H.; Ueta, Y.; Tachi, N.; Suzuki, T.; Watanabe, Y.; Hashimoto, Y. Visual Prognostic Factors in Eyes with Subretinal Fluid Associated with Branch Retinal Vein Occlusion. J. Clin. Med. 2023, 12, 2909. [Google Scholar] [CrossRef]
- Narayanan, R.; Stewart, M.W.; Chhablani, J.; Panchal, B.; Pappuru, R.R.; Das, T.; Jalali, S.; Ali, M.H. Baseline morphological characteristics as predictors of final visual acuity in patients with branch retinal vein occlusions: MARVEL report no. 3. Indian J. Ophthalmol. 2018, 66, 1291–1294. [Google Scholar] [CrossRef] [PubMed]
- Onishi, A.C.; Ashraf, M.; Soetikno, B.T.; Fawzi, A.A. Multilevel Ischemia in Disorganization of the Retinal Inner Layers on Projection-Resolved Optical Coherence Tomography Angiography. Retina 2019, 39, 1588–1594. [Google Scholar] [CrossRef]
- Farinha, C.; Marques, J.P.; Almeida, E.; Baltar, A.; Santos, A.R.; Melo, P.; Costa, M.; Figueira, J.; Cachulo, M.L.; Pires, I.; et al. Treatment of Retinal Vein Occlusion with Ranibizumab in Clinical Practice: Longer-Term Results and Predictive Factors of Functional Outcome. Ophthalmic Res. 2015, 55, 10–18. [Google Scholar] [CrossRef]
- Sophie, R.; Hafiz, G.; Scott, A.W.; Zimmer-Galler, I.; Nguyen, Q.D.; Ying, H.; Do, D.V.; Solomon, S.; Sodhi, A.; Gehlbach, P.; et al. Long-term outcomes in ranibizumab-treated patients with retinal vein occlusion; the role of progression of retinal nonperfusion. Am. J. Ophthalmol. 2013, 156, 693–705. [Google Scholar] [CrossRef]
- Chatziralli, I.; Theodossiadis, G.; Parikakis, E.; Mitropoulos, P.G.; Theodossiadis, P. Long-Term Anatomical and Functional Outcomes in Patients with Ischemic Central Retinal Vein Occlusion Treated with Anti-Vascular Endothelial Growth Factor Agents. Ophthalmic Res. 2017, 58, 203–208. [Google Scholar] [CrossRef]
- Larsen, M.; Waldstein, S.M.; Priglinger, S.; Hykin, P.; Barnes, E.; Gekkieva, M.; Das Gupta, A.; Wenzel, A.; Mones, J.; Group, C.S. Sustained Benefits from Ranibizumab for Central Retinal Vein Occlusion with Macular Edema: 24-Month Results of the CRYSTAL Study. Ophthalmol. Retina 2018, 2, 134–142. [Google Scholar] [CrossRef]
- Berry, D.; Thomas, A.S.; Fekrat, S.; Grewal, D.S. Association of Disorganization of Retinal Inner Layers with Ischemic Index and Visual Acuity in Central Retinal Vein Occlusion. Ophthalmol. Retina 2018, 2, 1125–1132. [Google Scholar] [CrossRef] [PubMed]
- Ding, X.; Li, J.; Hu, X.; Yu, S.; Pan, J.; Tang, S. Prospective study of intravitreal triamcinolone acetonide versus bevacizumab for macular edema secondary to central retinal vein occlusion. Retina 2011, 31, 838–845. [Google Scholar] [CrossRef]
- Ehrlich, R.; Ciulla, T.A.; Moss, A.M.; Harris, A. Combined treatment of intravitreal bevacizumab and intravitreal triamcinolone in patients with retinal vein occlusion: 6 months of follow-up. Graefes Arch. Clin. Exp. Ophthalmol. 2010, 248, 375–380. [Google Scholar] [CrossRef]
- Wang, H.Y.; Li, X.; Wang, Y.S.; Zhang, Z.F.; Li, M.H.; Su, X.N.; Zhu, J.T. Intravitreal injection of bevacizumab alone or with triamcinolone acetonide for treatment of macular edema caused by central retinal vein occlusion. Int. J. Ophthalmol. 2011, 4, 89–94. [Google Scholar] [CrossRef]
- Fan, C.; Wang, Y.; Ji, Q.; Zhao, B.; Xie, J. Comparison of clinical efficacy of intravitreal ranibizumab with and without triamcinolone acetonide in macular edema secondary to central retinal vein occlusion. Curr. Eye Res. 2014, 39, 938–943. [Google Scholar] [CrossRef]
- Spaide, R.F. Volume-Rendered Optical Coherence Tomography of Diabetic Retinopathy Pilot Study. Am. J. Ophthalmol. 2015, 160, 1200–1210. [Google Scholar] [CrossRef]
- Nicholson, L.; Ramu, J.; Triantafyllopoulou, I.; Patrao, N.V.; Comyn, O.; Hykin, P.; Sivaprasad, S. Diagnostic accuracy of disorganization of the retinal inner layers in detecting macular capillary non-perfusion in diabetic retinopathy. Clin. Exp. Ophthalmol. 2015, 43, 735–741. [Google Scholar] [CrossRef] [PubMed]
- Dodo, Y.; Murakami, T.; Uji, A.; Yoshitake, S.; Yoshimura, N. Disorganized retinal lamellar structures in nonperfused areas of diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 2015, 56, 2012–2020. [Google Scholar] [CrossRef]
- Balaratnasingam, C.; Inoue, M.; Ahn, S.; McCann, J.; Dhrami-Gavazi, E.; Yannuzzi, L.A.; Freund, K.B. Visual Acuity Is Correlated with the Area of the Foveal Avascular Zone in Diabetic Retinopathy and Retinal Vein Occlusion. Ophthalmology 2016, 123, 2352–2367. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Z.; Meng, Y.; Kozak, I.; Xie, M.; Liang, Y.; Yan, B.; Zhou, L.; Ouyang, P.; Yao, X.; Luo, J. Microvascular Structure Changes After Intravitreal Ranibizumab Injection in Retinal Vein Occlusion Patients With and Without Macular Ischemia. Front. Med. 2021, 8, 737537. [Google Scholar] [CrossRef]
- Sun, J.K.; Lin, M.M.; Lammer, J.; Prager, S.; Sarangi, R.; Silva, P.S.; Aiello, L.P. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014, 132, 1309–1316. [Google Scholar] [CrossRef] [PubMed]
- Grewal, D.S.; O’Sullivan, M.L.; Kron, M.; Jaffe, G.J. Association of Disorganization of Retinal Inner Layers With Visual Acuity In Eyes With Uveitic Cystoid Macular Edema. Am. J. Ophthalmol. 2017, 177, 116–125. [Google Scholar] [CrossRef] [PubMed]
- Santos, A.R.; Costa, M.A.; Schwartz, C.; Alves, D.; Figueira, J.; Silva, R.; Cunha-Vaz, J.G. Optical coherence tomography baseline predictors for initial best-corrected visual acuity response to intravitreal anti-vascular endothelial growth factor treatment in eyes with diabetic macular edema: The chartres Study. Retina 2018, 38, 1110–1119. [Google Scholar] [CrossRef] [PubMed]
- Narnaware, S.H.; Bawankule, P.K.; Raje, D. Short-term outcomes of intravitreal dexamethasone in relation to biomarkers in diabetic macular edema. Eur. J. Ophthalmol. 2021, 31, 1185–1191. [Google Scholar] [CrossRef] [PubMed]
- Chu, Y.K.; Hong, Y.T.; Byeon, S.H.; Kwon, O.W. In vivo detection of acute ischemic damages in retinal arterial occlusion with optical coherence tomography: A “prominent middle limiting membrane sign”. Retina 2013, 33, 2110–2117. [Google Scholar] [CrossRef]
- Abtahi, S.H.; Nourinia, R.; Mazloumi, M.; Nouri, H.; Arevalo, J.F.; Ahmadieh, H. Retinal ischemic cascade: New insights into the pathophysiology and imaging findings. Surv. Ophthalmol. 2023, 68, 380–387. [Google Scholar] [CrossRef]
- Yu, S.; Pang, C.E.; Gong, Y.; Freund, K.B.; Yannuzzi, L.A.; Rahimy, E.; Lujan, B.J.; Tabandeh, H.; Cooney, M.J.; Sarraf, D. The spectrum of superficial and deep capillary ischemia in retinal artery occlusion. Am. J. Ophthalmol. 2015, 159, e51–e52. [Google Scholar] [CrossRef]
- Burnasheva, M.A.; Maltsev, D.S.; Kulikov, A.N.; Sherbakova, K.A.; Barsukov, A.V. Association of Chronic Paracentral Acute Middle Maculopathy Lesions with Hypertension. Ophthalmol. Retina 2020, 4, 504–509. [Google Scholar] [CrossRef] [PubMed]
- Nourinia, R.; Mashhadi, S.M.; Abtahi, S.H.; Nouri, H. Are inner nuclear layer ischemic lesions hidden indicators of retinal vein occlusion risk? A case-control study. Int. J. Retin. Vitr. 2023, 9, 39. [Google Scholar] [CrossRef]
- Browning, D.J.; Punjabi, O.S.; Lee, C. Assessment of ischemia in acute central retinal vein occlusion from inner retinal reflectivity on spectral domain optical coherence tomography. Clin. Ophthalmol. 2017, 11, 71–79. [Google Scholar] [CrossRef]
- Itoh, Y.; Vasanji, A.; Ehlers, J.P. Volumetric ellipsoid zone mapping for enhanced visualisation of outer retinal integrity with optical coherence tomography. Br. J. Ophthalmol. 2016, 100, 295–299. [Google Scholar] [CrossRef]
- Etheridge, T.; Dobson, E.T.A.; Wiedenmann, M.; Oden, N.; VanVeldhuisen, P.; Scott, I.U.; Ip, M.S.; Eliceiri, K.W.; Blodi, B.A.; Domalpally, A. Ellipsoid Zone Defects in Retinal Vein Occlusion Correlates With Visual Acuity Prognosis: SCORE2 Report 14. Transl. Vis. Sci. Technol. 2021, 10, 31. [Google Scholar] [CrossRef] [PubMed]
- Chatziralli, I.; Theodossiadis, G.; Chatzirallis, A.; Parikakis, E.; Mitropoulos, P.; Theodossiadis, P. RANIBIZUMAB FOR RETINAL VEIN OCCLUSION: Predictive Factors and Long-Term Outcomes in Real-Life Data. Retina 2018, 38, 559–568. [Google Scholar] [CrossRef] [PubMed]
- Ciulla, T.A.; Kapik, B.; Grewal, D.S.; Ip, M.S. Visual Acuity in Retinal Vein Occlusion, Diabetic, and Uveitic Macular Edema: Central Subfield Thickness and Ellipsoid Zone Analysis. Ophthalmol. Retina 2021, 5, 633–647. [Google Scholar] [CrossRef]
- Ceklic, L.; Huf, W.; Ebneter, A.; Wolf, S.; Zinkernagel, M.S.; Munk, M.R. The impact of ganglion cell layer cysts in diabetic macular oedema treated with anti-vascular endothelial growth factor. Acta Ophthalmol. 2019, 97, e1041–e1047. [Google Scholar] [CrossRef]
- Munk, M.R.; Kiss, C.G.; Huf, W.; Montuoro, A.; Sulzbacher, F.; Kroh, M.; Larsen, M.; Schmidt-Erfurth, U. Visual acuity and microperimetric mapping of lesion area in eyes with inflammatory cystoid macular oedema. Acta Ophthalmol. 2014, 92, 332–338. [Google Scholar] [CrossRef]
- Ogino, K.; Murakami, T.; Tsujikawa, A.; Miyamoto, K.; Sakamoto, A.; Ota, M.; Yoshimura, N. Characteristics of optical coherence tomographic hyperreflective foci in retinal vein occlusion. Retina 2012, 32, 77–85. [Google Scholar] [CrossRef]
- Mo, B.; Zhou, H.Y.; Jiao, X.; Zhang, F. Evaluation of hyperreflective foci as a prognostic factor of visual outcome in retinal vein occlusion. Int. J. Ophthalmol. 2017, 10, 605–612. [Google Scholar] [CrossRef] [PubMed]
- Chatziralli, I.P.; Sergentanis, T.N.; Sivaprasad, S. Hyperreflective Foci as an Independent Visual Outcome Predictor in Macular Edema Due to Retinal Vascular Diseases Treated with Intravitreal Dexamethasone or Ranibizumab. Retina 2016, 36, 2319–2328. [Google Scholar] [CrossRef]
- Abraham, J.R.; Wykoff, C.C.; Arepalli, S.; Lunasco, L.; Yu, H.J.; Hu, M.; Reese, J.; Srivastava, S.K.; Brown, D.M.; Ehlers, J.P. Aqueous Cytokine Expression and Higher Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study. Am. J. Ophthalmol. 2021, 222, 328–339. [Google Scholar] [CrossRef]
- Kazantzis, D.; Sergentanis, T.N.; Machairoudia, G.; Dimitriou, E.; Kroupis, C.; Theodossiadis, G.; Theodossiadis, P.; Chatziralli, I. Correlation Between Imaging Morphological Findings and Laboratory Biomarkers in Patients with Retinal Vein Occlusion. Ophthalmol. Ther. 2023, 12, 1239–1249. [Google Scholar] [CrossRef] [PubMed]
- Agarwal, R.; Aurora, R.G.; Siswanto, B.B.; Muliawan, H.S. The prognostic value of neutrophil-to-lymphocyte ratio across all stages of coronary artery disease. Coron. Artery Dis. 2022, 33, 137–143. [Google Scholar] [CrossRef] [PubMed]
- Ilhan, N.; Daglioglu, M.C.; Ilhan, O.; Coskun, M.; Tuzcu, E.A.; Kahraman, H.; Keskin, U. Assessment of Neutrophil/Lymphocyte Ratio in Patients with Age-related Macular Degeneration. Ocul. Immunol. Inflamm. 2015, 23, 287–290. [Google Scholar] [CrossRef]
- Ulu, S.M.; Dogan, M.; Ahsen, A.; Altug, A.; Demir, K.; Acarturk, G.; Inan, S. Neutrophil-to-lymphocyte ratio as a quick and reliable predictive marker to diagnose the severity of diabetic retinopathy. Diabetes Technol. Ther. 2013, 15, 942–947. [Google Scholar] [CrossRef] [PubMed]
- Dursun, A.; Ozturk, S.; Yucel, H.; Ozec, A.V.; Dursun, F.G.; Toker, M.I.; Erdogan, H.; Arici, M.K.; Topalkara, A. Association of neutrophil/lymphocyte ratio and retinal vein occlusion. Eur. J. Ophthalmol. 2015, 25, 343–346. [Google Scholar] [CrossRef]
- Sahin, M.; Elbey, B.; Sahin, A.; Yuksel, H.; Turkcu, F.M.; Caca, I. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in retinal vein occlusion. Clin. Exp. Optom. 2020, 103, 490–494. [Google Scholar] [CrossRef]
- Zhu, D.D.; Liu, X. Neutrophil/Lymphocyte Ratio and Platelet/Lymphocyte Ratio in Branch Retinal Vein Occlusion. J. Ophthalmol. 2019, 2019, 6043612. [Google Scholar] [CrossRef]
- Dysli, M.; Ruckert, R.; Munk, M.R. Differentiation of Underlying Pathologies of Macular Edema Using Spectral Domain Optical Coherence Tomography (SD-OCT). Ocul. Immunol. Inflamm. 2019, 27, 474–483. [Google Scholar] [CrossRef] [PubMed]
- Munk, M.R.; Bolz, M.; Huf, W.; Sulzbacher, F.; Roberts, P.; Simader, C.; Ruckert, R.; Kiss, C.G. Morphologic and functional evaluations during development, resolution, and relapse of uveitis-associated cystoid macular edema. Retina 2013, 33, 1673–1683. [Google Scholar] [CrossRef]
- Noma, H.; Funatsu, H.; Mimura, T.; Shimada, K. Visual function and serous retinal detachment in patients with branch retinal vein occlusion and macular edema: A case series. BMC Ophthalmol. 2011, 11, 29. [Google Scholar] [CrossRef]
- Munk, M.R.; Kiss, C.G.; Steiner, I.; Sulzbacher, F.; Roberts, P.; Kroh, M.; Montuoro, A.; Simader, C.; Schmidt-Erfurth, U. Systematic correlation of morphologic alterations and retinal function in eyes with uveitis-associated cystoid macular oedema during development, resolution and relapse. Br. J. Ophthalmol. 2013, 97, 1289–1296. [Google Scholar] [CrossRef]
- Terao, N.; Koizumi, H.; Kojima, K.; Yamagishi, T.; Nagata, K.; Kitazawa, K.; Yamamoto, Y.; Yoshii, K.; Hiraga, A.; Toda, M.; et al. Association of Upregulated Angiogenic Cytokines With Choroidal Abnormalities in Chronic Central Serous Chorioretinopathy. Investig. Ophthalmol. Vis. Sci. 2018, 59, 5924–5931. [Google Scholar] [CrossRef] [PubMed]
- Baba, T.; Koyama, A.; Uotani, R.; Miyake, H.; Inata, K.; Sasaki, S.I.; Shimizu, Y.; Inoue, Y.; Adachi, K.; Nanba, E.; et al. Association of IL-4 with pachychoroid neovasculopathy. Sci. Rep. 2023, 13, 1152. [Google Scholar] [CrossRef] [PubMed]
- Kim, K.M.; Lee, M.W.; Lim, H.B.; Koo, H.M.; Shin, Y.I.; Kim, J.Y. Repeatability of measuring the vessel density in patients with retinal vein occlusion: An optical coherence tomography angiography study. PLoS ONE 2020, 15, e0234933. [Google Scholar] [CrossRef]
- Coscas, F.; Glacet-Bernard, A.; Miere, A.; Caillaux, V.; Uzzan, J.; Lupidi, M.; Coscas, G.; Souied, E.H. Optical Coherence Tomography Angiography in Retinal Vein Occlusion: Evaluation of Superficial and Deep Capillary Plexa. Am. J. Ophthalmol. 2016, 161, 160–171.e2. [Google Scholar] [CrossRef]
- Cabral, D.; Coscas, F.; Glacet-Bernard, A.; Pereira, T.; Geraldes, C.; Cachado, F.; Papoila, A.; Coscas, G.; Souied, E. Biomarkers of Peripheral Nonperfusion in Retinal Venous Occlusions Using Optical Coherence Tomography Angiography. Transl. Vis. Sci. Technol. 2019, 8, 7. [Google Scholar] [CrossRef]
- Adhi, M.; Filho, M.A.; Louzada, R.N.; Kuehlewein, L.; de Carlo, T.E.; Baumal, C.R.; Witkin, A.J.; Sadda, S.R.; Sarraf, D.; Reichel, E.; et al. Retinal Capillary Network and Foveal Avascular Zone in Eyes with Vein Occlusion and Fellow Eyes Analyzed With Optical Coherence Tomography Angiography. Investig. Ophthalmol. Vis. Sci. 2016, 57, OCT486–OCT494. [Google Scholar] [CrossRef]
- Ouederni, M.; Khalifa, M.B.H.; Sassi, H.; Nefaa, F.; Ayed, O.; Cheour, M. Quantitative Analysis of Microvascular Network with Optical Coherence Tomography Angiography and its Correlation with Visual Acuity in Retinal Vein Occlusion. J. Curr. Ophthalmol. 2021, 33, 453–460. [Google Scholar] [CrossRef] [PubMed]
- Seknazi, D.; Coscas, F.; Sellam, A.; Rouimi, F.; Coscas, G.; Souied, E.H.; Glacet-Bernard, A. OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN RETINAL VEIN OCCLUSION: Correlations Between Macular Vascular Density, Visual Acuity, and Peripheral Nonperfusion Area on Fluorescein Angiography. Retina 2018, 38, 1562–1570. [Google Scholar] [CrossRef]
- Wakabayashi, T.; Sato, T.; Hara-Ueno, C.; Fukushima, Y.; Sayanagi, K.; Shiraki, N.; Sawa, M.; Ikuno, Y.; Sakaguchi, H.; Nishida, K. Retinal Microvasculature and Visual Acuity in Eyes With Branch Retinal Vein Occlusion: Imaging Analysis by Optical Coherence Tomography Angiography. Investig. Ophthalmol. Vis. Sci. 2017, 58, 2087–2094. [Google Scholar] [CrossRef]
- Winegarner, A.; Wakabayashi, T.; Hara-Ueno, C.; Sato, T.; Busch, C.; Fukushima, Y.; Sayanagi, K.; Nishida, K.; Sakaguchi, H.; Nishida, K. RETINAL MICROVASCULATURE AND VISUAL ACUITY AFTER INTRAVITREAL AFLIBERCEPT IN EYES WITH CENTRAL RETINAL VEIN OCCLUSION: An Optical Coherence Tomography Angiography Study. Retina 2018, 38, 2067–2072. [Google Scholar] [CrossRef] [PubMed]
- Hasegawa, T.; Takahashi, Y.; Maruko, I.; Kogure, A.; Iida, T. Macular vessel reduction as predictor for recurrence of macular oedema requiring repeat intravitreal ranibizumab injection in eyes with branch retinal vein occlusion. Br. J. Ophthalmol. 2019, 103, 1367–1372. [Google Scholar] [CrossRef] [PubMed]
- Tsuboi, K.; Ishida, Y.; Kamei, M. Gap in Capillary Perfusion on Optical Coherence Tomography Angiography Associated With Persistent Macular Edema in Branch Retinal Vein Occlusion. Investig. Ophthalmol. Vis. Sci. 2017, 58, 2038–2043. [Google Scholar] [CrossRef]
- Tomita, R.; Iwase, T.; Goto, K.; Yamamoto, K.; Ra, E.; Terasaki, H. Correlation between macular vessel density and number of intravitreal anti-VEGF agents for macular edema associated with branch retinal vein occlusion. Sci. Rep. 2019, 9, 16388. [Google Scholar] [CrossRef]
- Sakimoto, S.; Kamei, M.; Suzuki, M.; Yano, S.; Matsumura, N.; Sakaguchi, H.; Gomi, F.; Nishida, K. Relationship between grades of macular perfusion and foveal thickness in branch retinal vein occlusion. Clin. Ophthalmol. 2013, 7, 39–45. [Google Scholar] [CrossRef] [PubMed]
- Lim, H.B.; Kim, M.S.; Jo, Y.J.; Kim, J.Y. Prediction of Retinal Ischemia in Branch Retinal Vein Occlusion: Spectral-Domain Optical Coherence Tomography Study. Investig. Ophthalmol. Vis. Sci. 2015, 56, 6622–6629. [Google Scholar] [CrossRef]
- Schmid, H.; Renner, M.; Dick, H.B.; Joachim, S.C. Loss of inner retinal neurons after retinal ischemia in rats. Investig. Ophthalmol. Vis. Sci. 2014, 55, 2777–2787. [Google Scholar] [CrossRef]
- Suzuki, N.; Hirano, Y.; Yoshida, M.; Tomiyasu, T.; Uemura, A.; Yasukawa, T.; Ogura, Y. Microvascular Abnormalities on Optical Coherence Tomography Angiography in Macular Edema Associated With Branch Retinal Vein Occlusion. Am. J. Ophthalmol. 2016, 161, 126–132.e121. [Google Scholar] [CrossRef]
- Samara, W.A.; Shahlaee, A.; Sridhar, J.; Khan, M.A.; Ho, A.C.; Hsu, J. Quantitative Optical Coherence Tomography Angiography Features and Visual Function in Eyes With Branch Retinal Vein Occlusion. Am. J. Ophthalmol. 2016, 166, 76–83. [Google Scholar] [CrossRef]
- Choi, K.E.; Yun, C.; Cha, J.; Kim, S.W. OCT angiography features associated with macular edema recurrence after intravitreal bevacizumab treatment in branch retinal vein occlusion. Sci. Rep. 2019, 9, 14153. [Google Scholar] [CrossRef]
- Suzuki, N.; Hirano, Y.; Tomiyasu, T.; Esaki, Y.; Uemura, A.; Yasukawa, T.; Yoshida, M.; Ogura, Y. Retinal Hemodynamics Seen on Optical Coherence Tomography Angiography Before and After Treatment of Retinal Vein Occlusion. Investig. Ophthalmol. Vis. Sci. 2016, 57, 5681–5687. [Google Scholar] [CrossRef] [PubMed]
- Vujosevic, S.; Toma, C.; Villani, E.; Muraca, A.; Torti, E.; Florimbi, G.; Leporati, F.; Brambilla, M.; Nucci, P.; De Cilla, S. Diabetic macular edema with neuroretinal detachment: OCT and OCT-angiography biomarkers of treatment response to anti-VEGF and steroids. Acta Diabetol. 2020, 57, 287–296. [Google Scholar] [CrossRef] [PubMed]
- Zhao, X.Y.; Zhao, Q.; Wang, C.T.; Meng, L.H.; Cheng, S.Y.; Gu, X.W.; Sadda, S.R.; Chen, Y.X. Central and Peripheral Changes in Retinal Vein Occlusion and Fellow Eyes in Ultra-Widefield Optical Coherence Tomography Angiography. Investig. Ophthalmol. Vis. Sci. 2024, 65, 6. [Google Scholar] [CrossRef]
- Casselholmde Salles, M.; Kvanta, A.; Amren, U.; Epstein, D. Optical Coherence Tomography Angiography in Central Retinal Vein Occlusion: Correlation Between the Foveal Avascular Zone and Visual Acuity. Investig. Ophthalmol. Vis. Sci. 2016, 57, OCT242–OCT246. [Google Scholar] [CrossRef] [PubMed]
- Fan, L.; Zhu, Y.; Liao, R. Evaluation of macular microvasculature and foveal avascular zone in patients with retinal vein occlusion using optical coherence tomography angiography. Int. Ophthalmol. 2022, 42, 211–218. [Google Scholar] [CrossRef] [PubMed]
- Ghasemi Falavarjani, K.; Iafe, N.A.; Hubschman, J.P.; Tsui, I.; Sadda, S.R.; Sarraf, D. Optical Coherence Tomography Angiography Analysis of the Foveal Avascular Zone and Macular Vessel Density After Anti-VEGF Therapy in Eyes With Diabetic Macular Edema and Retinal Vein Occlusion. Investig. Ophthalmol. Vis. Sci. 2017, 58, 30–34. [Google Scholar] [CrossRef]
- Kwan, C.C.; Fawzi, A.A. Imaging and Biomarkers in Diabetic Macular Edema and Diabetic Retinopathy. Curr. Diabetes Rep. 2019, 19, 95. [Google Scholar] [CrossRef]
- Noma, H.; Yasuda, K.; Shimura, M. Cytokines and the Pathogenesis of Macular Edema in Branch Retinal Vein Occlusion. J. Ophthalmol. 2019, 2019, 5185128. [Google Scholar] [CrossRef]
- Priglinger, S.G.; Wolf, A.H.; Kreutzer, T.C.; Kook, D.; Hofer, A.; Strauss, R.W.; Alge, C.S.; Kunze, C.; Haritoglou, C.; Kampik, A. Intravitreal bevacizumab injections for treatment of central retinal vein occlusion: Six-month results of a prospective trial. Retina 2007, 27, 1004–1012. [Google Scholar] [CrossRef]
- Noma, H.; Mimura, T.; Yasuda, K.; Nakagawa, H.; Motohashi, R.; Kotake, O.; Shimura, M. Intravitreal Ranibizumab and Aqueous Humor Factors/Cytokines in Major and Macular Branch Retinal Vein Occlusion. Ophthalmologica 2016, 235, 203–207. [Google Scholar] [CrossRef]
- Bhisitkul, R.B.; Campochiaro, P.A.; Shapiro, H.; Rubio, R.G. Predictive value in retinal vein occlusions of early versus late or incomplete ranibizumab response defined by optical coherence tomography. Ophthalmology 2013, 120, 1057–1063. [Google Scholar] [CrossRef] [PubMed]
Predictive Biomarkers | Predictor of Good Response to Anti-VEGF | Predictor of Good Response to Steroids | References |
---|---|---|---|
Thicker (>570 µm) CRT at baseline and/or at follow up | NO | YES | [104,105,106,107] |
p-MLM sign | no data, may indicate high treatment need for anti-VEGF | no data | [108] |
Loss of EZ integrity | NO | no data | [5,109,110,111] |
Presence of intraretinal cysts | NO | no data | [112] |
HRF | NO | YES | [109,113,114,115,116,117] |
Persistent SRF | NO | YES | [113] |
Choroidal thickness >300 micrometers | NO | no data | [118] |
Extensive FA leakage within the macula | NO | no data | [107] |
Higher levels of VEGF and EPO | YES | NO | [24,52,59,64,97,99] |
Higher aqueous levels of IL-6, IL-12, IL-13, MCP-1, ICAM-1, IP-10, PTX 3 | NO | YES | [27,30,49,52,57,58,59,65,69,70,71] |
Prognostic Biomarkers for Poor Visual Outcome | References |
---|---|
Greater extent of DRIL (greater later in the course of treatment) | [119,120,121] |
Presence of p-MLM sign | [122] |
Loss of EZ | [123,124] |
Presence of intraretinal cysts (especially in the GCL) | [112,125] |
Presence of HRF | [126] |
Macular non-perfusion on FA | [127,128,129] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Munk, M.R.; Ceklic, L.; Stillenmunkes, R.; Chaudhary, V.; Waheed, N.; Chhablani, J.; de Smet, M.D.; Tillmann, A. Integrated Assessment of OCT, Multimodal Imaging, and Cytokine Markers for Predicting Treatment Responses in Retinal Vein Occlusion Associated Macular Edema: A Comparative Review of Anti-VEGF and Steroid Therapies. Diagnostics 2024, 14, 1983. https://doi.org/10.3390/diagnostics14171983
Munk MR, Ceklic L, Stillenmunkes R, Chaudhary V, Waheed N, Chhablani J, de Smet MD, Tillmann A. Integrated Assessment of OCT, Multimodal Imaging, and Cytokine Markers for Predicting Treatment Responses in Retinal Vein Occlusion Associated Macular Edema: A Comparative Review of Anti-VEGF and Steroid Therapies. Diagnostics. 2024; 14(17):1983. https://doi.org/10.3390/diagnostics14171983
Chicago/Turabian StyleMunk, Marion R., Lala Ceklic, Richard Stillenmunkes, Varun Chaudhary, Nadia Waheed, Jay Chhablani, Marc D. de Smet, and Anne Tillmann. 2024. "Integrated Assessment of OCT, Multimodal Imaging, and Cytokine Markers for Predicting Treatment Responses in Retinal Vein Occlusion Associated Macular Edema: A Comparative Review of Anti-VEGF and Steroid Therapies" Diagnostics 14, no. 17: 1983. https://doi.org/10.3390/diagnostics14171983