Effect of mitochondrial haplogroups on ranibizumab response in neovascular age‐related macular degeneration patients: a pilot study

Abstract

322 AE 95 lm at baseline. A reduction of 52 lm became apparent within the first year and remained at 250 AE 102 lm on average in year 5 ( Fig. 1E).We report on a representative number of eyes complicated by nAMD and treated with a personalized PRN regimen for at least 5 years without discontinuation. Moderate visual decline was achieved through an individualized monitoring and retreatment scheme based on empiric variable intervals for each patient. Advantages of this strategy imply a direct response to activity independent of an early or late stage disease while reducing expenses of anti-VEGF treatment and maximizing safety. Our adopted methodthough reactive in treatment modalityis somewhat between monthly PRN and proactive treat and extend. Only a few comparative reviews have been published until today with short-term efficacy outcomes (Chin-Yee et al. 2016; Danyliv et al. 2017).In conclusion, our real-world data confirm the potential benefit of a personalized PRN regimen. It combines a fairly low injection rate with an acceptable clinical effort. Ethical ApprovalAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. ReferencesBrown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T; ANCHOR Study Group (2009): Ranibizumab versus verteporfin photodynamic therapy for neovascular agerelated macular degeneration: two-year results of the ANCHOR study. Ophthalmology 116: 57-65.e5. Chin-Yee D, Eck T, Fowler S, Hardi A & Apte RS (2016): A systematic review of as needed versus treat and extend ranibizumab or bevacizumab treatment regimens for neovascular age-related macular degeneration. Br J Ophthalmol 100: 914-917. Danyliv A, Glanville J, McCool R, Ferreira A, Skelly A & Jacob RP (2017): The clinical effectiveness of ranibizumab treat and extend regimen in nAMD: systematic review and network meta-analysis. Adv Ther 34:

Oxidative phosphorylation inducers fight pathological angiogenesis

“…For example, as discussed earlier, OXPHOS capability was lower in cybrids from the JT haplogroup [57] and OXPHOS electron transport rate was higher in cybrids from the U haplogroup [58]. Interestingly, the JT haplogroup appears to be a susceptibility factor for nAMD [59], and individuals from this haplogroup showed a worse response to nAMD intravitreal ranibizumab therapy [3]. By contrast, the U haplogroup appears to be a resistance factor for proliferative diabetic retinopathy [60,61], and individuals from this haplogroup showed a better response to nAMD intravitreal ranibizumab therapy [3].…”

“…Interestingly, the JT haplogroup appears to be a susceptibility factor for nAMD [59], and individuals from this haplogroup showed a worse response to nAMD intravitreal ranibizumab therapy [3]. By contrast, the U haplogroup appears to be a resistance factor for proliferative diabetic retinopathy [60,61], and individuals from this haplogroup showed a better response to nAMD intravitreal ranibizumab therapy [3]. In RA, radiographic erosions were significantly associated with the JT haplogroup [62] and, in early RA, an association was reported between erosions and increased intraarticular blood flow [63].…”

“…If this is the case, the increased injection number might reflect refractory cases that respond poorly to ranibizumab. In patients with nAMD, the mitochondrial DNA (mtDNA) genetic background or haplogroup also modifies the response to intravitreal ranibizumab therapy [3]. At 4 months, in all haplogroups, best corrected visual acuity and central foveal thickness (CFT) values were higher and lower than basal values, respectively.…”

The Role of Mitochondrial DNA Variation in Drug Response: A Systematic Review

“…The remaining six articles spanned the areas of age-related macular degeneration, migraines, schizophrenia, thromboembolic disease, hepatitis C infection and menopausal symptoms (4.2% each). Gender distribution across studies tended to skew toward a male majority with the exception of seven studies (Di Lorenzo et al, 2009;Kampira et al, 2013a,b;Subiabre et al, 2015;Esteban et al, 2019;Wang et al, 2019;Abedi et al, 2020), one of which was concerned with the management of menopausal symptoms and thus enrolled female participants exclusively (Wang et al, 2019). In terms of study design, with the exception of six studies that used in cytoplasmic hybrid (cybrid) in vitro models, the remaining 18 articles examined drug responses across patient cohorts.…”

“…In comparison, seven articles included black or African-American subjects (29.2%), three articles included Latino or Hispanic subjects (12.5%), three articles included Asian subjects (12.5%) and one article included those of Amerindian descent (4.2%). In the case of two publications, the ethnic origins of the study participants were not clearly stated (Sun et al, 2015;Esteban et al, 2019).…”