title: Photodynamic therapy in VEGF inhibition non-responders-Pharmacogenetic study in age-related macular degeneration assessed with swept-source optical coherence tomography.
abstract: BACKGROUND
  Treatment of neovascular age-related macular degeneration (nAMD) remains a major challenge in ophthalmology. It is essential to determine which of VEGF inhibition non-responders can benefit from photodynamic therapy (PDT). As AMD is strongly related to gene polymorphisms, genetic factors can modify efficacy of treatment. Swept-source optical coherence tomography (SS-OCT) gives exceptional insight into the retina and choroid. SS-OCT usefulness needs to be evaluated in nAMD patients.
  
  
  METHODS
  Prospective 6-month study included consecutive 110 patients (110 eyes) with predominantly classic neovascular AMD treated with photodynamic therapy. Only non-responders to anti-VEGF were included in the study. Greatest linear dimension (GLD) of the lesion, best corrected visual acuity (BCVA), central subfield macular thickness (CSMT) and central choroidal thickness were assessed and compared between CFH and ARMS2 genotype groups. Success rate was the main endpoint. It was defined as not active CNV in the center of the fovea and no worsening in BCVA. Multiple regression was used to assess gene polymorphisms influence on PDT results. Wilcoxon tests were performed to determine significance of changes from baseline values.
  
  
  RESULTS
  Following genotype frequencies were obtained-CFH CC 35 patients (31.8%), CT 52 (47.3%), TT 23 (20.9%); ARMS2 TT 28 patients (25.4%), GT 43 (39.1%), GG 39 (35.4%) success rate in CC/CT/TT CFH and TT/GT/GG ARMS2 groups were as follows respectively: 22.9%, 28.8%, 30.4% and 28.6%, 25.6%, 28.2%. The differences were not significant with highest odds ratio TT vs. CC CFH 1.57 (95% CI 0.48-5.2, p=0.4). Significant increase in GLD was observed only in CC CFH group. Overall mean following measured parameters were obtained at baseline/day 7/month 3/month 6 (significant changes from baseline are marked with asterisk): GLD-3825±1301μm/3901±1579μm/3861±1463μm/3925±1523μm; CSMT-405±203μm/434±257μm*/321±163μm*/295±157*μm; CCT-235±103μm/278±157*μm/211±113μm*/201±107*μm; BCVA-49.3±12.5/43.2±14.2*/49.6±11.6/48.7±12.2 letters on ETDRS charts. In all patients classic component of the lesion was assessed with SS-OCT with no need to be reaffirmed in FA. Thus FA was used mainly for lesion size calculation.
  
  
  CONCLUSIONS
  Common genetic factors seem not to influence PDT effectiveness in VEGF inhibitors non-responders. SS-OCT is a valuable tool of nAMD monitoring, especially for choroid assessment. Deterioration of retinal structure and function is observed one week after PDT. It is related to increase in both retinal and choroidal thickness and is accompanied by mild temporary BCVA decrease.
authors.affiliation: Clinical Department of Ophthalmology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Ul. Panewnicka 65, 40-760 Katowice, Poland; Department of Ophthalmology, District Railway Hospital in Katowice, Ul. Panewnicka 65, 40-760 Katowice, Poland. Electronic address: slawomir.teper@sum.edu.pl.
authors.forename: Slawomir J
authors.initials: SJ
authors.lastname: Teper
authors.affiliation: Clinical Department of Ophthalmology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Ul. Panewnicka 65, 40-760 Katowice, Poland; Department of Ophthalmology, District Railway Hospital in Katowice, Ul. Panewnicka 65, 40-760 Katowice, Poland. Electronic address: atrum2@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Nowinska
authors.affiliation: Department of Ophthalmology, District Railway Hospital in Katowice, Ul. Panewnicka 65, 40-760 Katowice, Poland. Electronic address: jaroslaw.pilat6@gmail.com.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Pilat
authors.affiliation: Clinical Department of Ophthalmology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Ul. Panewnicka 65, 40-760 Katowice, Poland; Department of Ophthalmology, District Railway Hospital in Katowice, Ul. Panewnicka 65, 40-760 Katowice, Poland. Electronic address: wylegala@gmail.com.
authors.forename: Edward
authors.initials: E
authors.lastname: Wylegala
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008268:Macular Degeneration / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D000071185:Pharmacogenomic Testing; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D041623:Tomography, Optical Coherence / Q000379:methods*; D017211:Treatment Failure; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: C514392:ARMS2 protein, human; D020533:Angiogenesis Inhibitors; C493495:CFH protein, human; D017319:Photosensitizing Agents; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A; D017242:Complement Factor H
keywords: ARMS2; Age-related macular degeneration; CFH; Pharmacogenetics; Photodynamic therapy; Swept-source optical coherence tomography