Managing Neovascular Age-Related Macular Degeneration: Is More Research Needed to Improve Real-world Practice?

Abstract

Population-based data from registries of blind people confirm that antiangiogenic therapy has had a substantial role in reducing the burden of vision loss in patients with neovascular age-related macular degeneration (AMD).1 These data are also affirmed by results obtainedfromrandomizedclinical trials (RCTs). However, in contrast to RCTs, patientrelevantoutcomes fromobservational studies indicate that the initial gain in visual acuity (VA) is not maintained after a few years in thesepatient populations.A comprehensive analysis2 of real-world ranibizumab study data confirmed that patientrelevant outcomes are considerably poorer in observational studies than those reported in RCTs using fixed or as-needed (PRN) regimens, meaning that patients with neovascular AMD are often undertreated and undermonitored in many settings. Obviously, thebest strategy tomaximize the treatment effectof intravitreal antiangiogenicdrugs is fixed treatmentwith frequent injections, suchasmonthly ranibizumab. InPRNregimens, frequent (preferably monthly) monitoring is mandatory for themost effective treatmentoutcome. In clinical practice, extended follow-up intervalsmaybea threat to sustained VA, especially in patientswithdisease recurrence after an initially good response. In addition, the extent to which variation of care may hamper timely neovascular AMD diagnosis and their referral to retinal specialists is unknown. Published research3 suggests that social deprivation also acts as a potential barrier in accessinghealth care in patientswith this blinding condition. Therefore, health care policymakers should be aware of this medical issue. An early self-diagnosis test may possibly help patients becomeaware of the early signs of neovascularAMDor its recurrenceafter intravitreal treatment.Assessments of home-monitoring devices have been conducted, some of which provided encouraging results.4 Asystematic review5basedonhead-to-headstudiesofPRN comparedwithmonthly treatment found that PRN regimens, withmonthlymonitoring to guide retreatment, result in similar positive outcomes comparedwithmonthly treatment. The difference in VA was only 1.9 letters, favoring monthly treatment (95% CI, 0.5-3.3 letters), which is statistically significant but not clinically meaningful. This finding is important for physicians because indirect evidence fromRCTs suggests that patients in PRN studies with less strict monitoring, such as theSAILORstudy,or fixedquarterly injections, suchasPIER, did notmaintain average vision improvement after the first 3 monthly injections.2 In this issue of JAMA Ophthalmology, Stoller et al6 retrospectively analyze the data from HARBOR (Study of RanibizumabAdministeredMonthly or on anAs-neededBasis in Patients With Subfoveal Neovascular Age-related Macular Degeneration) anddescribe thecharacteristics ofpatientswho gained at least 15EarlyTreatmentDiabeticRetinopathy Study letters at 3monthsor later in the first year. Thesepatientswere respectively defined as early (within 3 months) or delayed (3 to 12months) responders andwere 25.2% and 13.7%of all patients, respectively. Thus, overall, 37.9%of patients gained 15 ormore letters at 12months.HARBORalso found that only approximately 5%ofpatients lost 15ormore letters at 12months. Therefore, the final VA of approximately 55% of patients was within±15 letters of baselineVAat 12months. They found that smaller lesionswith thicker retina and lowerVAatbaseline are found in early responders, whereas late responders more oftenhavepigment epithelial detachment. These findings in relation to early and late responders might be useful because identifyingpredictorsofdelayedVAgaincouldencouragephysicians to continue intensive treatment in an attempt tomaximizethepatient’sbenefit, rather thanswitchtoadifferentdrug. The limitation of these analyses is that they are restricted to a subgroup of responders and do not exploit the whole inRelated article page 545 Visual and Anatomical Response to Ranibizumab Original Investigation Research