title: Topical Dorzolamide-Timolol With Intravitreous Anti-Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration.
abstract: OBJECTIVE
  There is a subset of eyes with neovascular age-related macular degeneration (AMD) that have persistent exudation despite fixed-interval intravitreous anti-vascular endothelial growth factor (VEGF) injections.
  
  
  OBJECTIVE
  To evaluate the effect of topical dorzolamide hydrochloride-timolol maleate on anatomic and functional outcomes in eyes with neovascular AMD and incomplete response to anti-VEGF therapy.
  
  
  METHODS
  An exploratory, prospective single-arm interventional study at a tertiary referral academic private practice. Patients with neovascular AMD and persistent macular edema despite fixed-interval intravitreous anti-VEGF therapy were enrolled. Baseline spectral-domain optical coherence tomography and clinical data, including visual acuity and intraocular pressure, were obtained at enrollment and from one visit before enrollment. The study was performed at the Retina Service of Wills Eye Hospital and the offices of Mid Atlantic Retina from February 1, 2015, through September 30, 2015. Patients were followed up for at least 2 visits after enrollment. Central subfield thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height from spectral-domain optical coherence tomography were recorded at each visit.
  
  
  METHODS
  Enrolled eyes received a regimen of topical dorzolamide-timolol twice daily and continued to receive the same intravitreous anti-VEGF therapy at the same interval as received before enrollment for the duration of the study.
  
  
  METHODS
  Change in central subfield thickness was the primary outcome measure. Changes in maximum subretinal fluid height, maximum pigment epithelial detachment height, and visual acuity were the secondary outcome measures.
  
  
  RESULTS
  Ten patients (10 eyes) completed the study. The mean age of the patients was 78.2 years (age range, 65-91 years), and 6 were male. Eight eyes received intravitreous aflibercept, and 2 eyes received intravitreous ranibizumab. All study eyes had been receiving long-term anti-VEGF therapy with the same medication before study enrollment for a mean of 21.9 injections. The mean central subfield thickness decreased from 419.7 μm at enrollment to 334.1 μm at the final visit (P = .01). The mean maximum subretinal fluid height decreased from 126.6 μm at enrollment to 49.5 μm at the final visit (P = .02). The mean maximum pigment epithelial detachment height decreased from 277.4 μm at enrollment to 239.9 μm at the final visit (P = .12). The mean logMAR visual acuity were 0.54 at enrollment and 0.48 at the final visit (P = .60).
  
  
  CONCLUSIONS
  These data suggest that topical dorzolamide-timolol may reduce central subfield thickness and subretinal fluid in eyes with persistent exudation despite consistent, fixed-interval intravitreous anti-VEGF treatment for neovascular AMD.
authors.affiliation: Retina Service, Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Jayanth
authors.initials: J
authors.lastname: Sridhar
authors.affiliation: Retina Service, Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Jason
authors.initials: J
authors.lastname: Hsu
authors.affiliation: Retina Service, Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Abtin
authors.initials: A
authors.lastname: Shahlaee
authors.affiliation: Retina Service, Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Sunir J
authors.initials: SJ
authors.lastname: Garg
authors.affiliation: Retina Service, Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Spirn
authors.affiliation: Retina Service, Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Fineman
authors.affiliation: Retina Service, Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: James
authors.initials: J
authors.lastname: Vander
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D011446:Prospective Studies; D000069579:Ranibizumab / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D018570:Risk Assessment; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D013999:Timolol / Q000627:therapeutic use*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*
chemical_list: D004338:Drug Combinations; D011993:Recombinant Fusion Proteins; D013449:Sulfonamides; D013876:Thiophenes; D042461:Vascular Endothelial Growth Factor A; C479140:dorzolamide-timolol combination; C533178:aflibercept; D013999:Timolol; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab