Recurrence of ROP after Anti-VEGF Therapy: How Many, Which Ones, When, What, Where

Transcription

1 Recurrence of ROP after Anti-VEGF Therapy: How Many, Which Ones, When, What, Where Helen Mintz-Hittner, M.D. Department of Ophthalmology and Visual Science University of Texas-Health Science Center-Houston McGovern Medical School AAPOS-2016-Vancouver April 8th, 2016 I have no relevant financial relationships to disclose nor conflicts of interest to resolve. Helen Mintz Hittner, MD 1

2 Screening and Treatment with Anti-VEGF Screening: initial and follow-up: according to usual guidelines for active ROP. Treatment: at ETROP Type 1 (appropriate if Classical Stages or APROP is present): NOT BEFORE VEGF levels must be definitely increased must allow normal vascularization. NOT AFTER VEGF levels will eventually decrease contraction of substantial membrane formation will cause retinal detachment. Normal Inner Retinal Vascularization is Related to Gestational Age Precursors of inner retinal vessels arise from the optic disc at 14 weeks GA and reach the temporal ora serrata at 27 weeks GA. Anticipate avascular retina to be from 3 to 5 DD if <27 weeks GA. Laser of the undifferentiated peripheral avascular retina is unnecessary even if avascular retina is more than 2 DD (normal for term infants) increased DD of avascular retina is related to decreased GA. Helen Mintz Hittner, MD 2

3 20 wk 25 wk 30 wk 35 wk 40 wk Best Outcomes with Bevacizumab Monotherapy: 1. Larger visual fields because no peripheral retinal destruction; 2. Less myopia because AC growth factors not destroyed in peripheral retina. Worst Outcomes with Bevacizumab Monotherapy: Recurrence: **** Helen Mintz Hittner, MD 3

4 Factors Related to Recurrence Drug Selection Larger molecules will stay longer in the eye and in the blood (? in vulnerable tissues) with decreased # of recurrences. Smaller molecules may not stay long enough to allow completion of retinal vascularization) with increased # of recurrences. Factors Related to Recurrence Dose selection Higher dose may be associated with longer time before recurrences occur with decreased # of recurrences. Lower dose may be associated with shorter time before recurrences occur with increased # of recurrences. Helen Mintz Hittner, MD 4

5 Observations Regarding Recurrence Intravitreal bevacizumab monotherapy, especially in zone I, is beneficial; however, recurrences can cause adverse outcomes: How Many: Incidence is 8% infants; 7% eyes. Which Ones: Risk Factors are: 1) APROP; 2) Increased duration of hospital stay (cumulative adverse events); 3) Decreased birth weight When: Risk Period is from 45 to 55 wks AA ( 94%). Helen Mintz Hittner, MD 5

6 What: Characteristics of Recurrence: 1. Plus disease returns and does not go away (not similar to after the first treatment) 2. Intravitreal Neovascularization returns but will go away (similar to after the first treatment) Where: 2 sites: 1. Advancing Edge 2. Former Ridge and EFP Complex Rate of Growth of Advancing Edge is Important Recurrence: Advancing edge grows at a rate of 0.11 DD/wk [usually resulting in a retinal vascularization length of 1.76 DD beyond its location at the time of 1 st injection ]. No Recurrence: Advancing edge grows at a rate of 0.23 DD/wk [usually resulting in retinal vascularization length of 4.48 DD beyond its location at the time of 1 st injection]. Helen Mintz Hittner, MD 6

7 Stage 3+: At time of 2 nd Injection: At 2 Locations: Both the Advancing Edge And the Former Ridge and EFP Complex (Distance traveled from 1 st Rx to 2 nd Rx DD/wk) Initial Treatment: 35.1 wk AA (470 gm BW; 24 wk GA) Recurrence FA: 52.7 wk AA APROP: At time of 2 nd Injection: At 1 Location: Only the Advancing Edge (Distance traveled from 1 st Rx to 2 nd Rx DD/wk) Initial Treatment: 34.0 wk AA (450 gm BW; 23 wk GA) Recurrence FA: 48.9 wk AA Helen Mintz Hittner, MD 7

8 Stage 3+: 1 Injection (Distance traveled from 1 st Rx to 2 nd Rx DD/wk) Initial Treatment: 35.6 wk AA (495 gm BW; 23 wk GA) Final Appearance: 79.6 wk AA XX XX APROP: 1 Injection (Distance traveled from 1 st Rx to 2 nd Rx DD/wk) Initial Treatment: 32.9 wk AA (470 gm BW; 23 wk GA) Final Appearance: 83.3 wk AA XX XX Helen Mintz Hittner, MD 8