Retinopathy of Prematurity. Objectives. Normal Retina Development. ROP Pathogenesis 6/8/2018. Thomas W. Hejkal, MD, PhD Eye Consultants, PC

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Retinopathy of Prematurity Thomas W. Hejkal, MD, PhD Eye Consultants, PC Chair Emeritus Department of Ophthalmology UNMC drhejkal@eyeconsultantspc.

1 Retinopathy of Prematurity Thomas W. Hejkal, MD, PhD Eye Consultants, PC Chair Emeritus Department of Ophthalmology UNMC (No commercial interests) Objectives Identify risk factors and preventive strategies List current screening recommendations Discuss levels of severity of ROP Compare efficacy and risks of current treatment options Present current information to parents Normal Retina Development 16 weeks gestation Capillaries begin growth outward from the optic nerve weeks Vessels reach nasal ora serrata weeks Vessels reach temporal ora (mature) ROP Pathogenesis 1. Oxygen and nutrient supply to retina become insufficient 2. Inner retina becomes hypoxic Increased Vascular Endothelial Growth Factor (VEGF) 3. Abnormal blood vessels grow Bleeding and fibrosis 4. Retinal traction and detachment 1

2 Risk Factors Low birth weight Extreme prematurity (Low birth EGA) High oxygen levels Poor post natal weight gain Formula vs. breast milk Oxygen Level Lower vs. Higher O 2 Saturation Target (88-92%) vs. (91-95%) Significant decrease in severe ROP! Significant increase in mortality!! (Manley, et al. 2016, J Ped.; Fang JL, et al. 2016, Pediatrics) Weight Gain Low weight gain correlated with risk of severe ROP Models for screening based on Birth EGA Birth weight Weight gain per day / week Cao JH, et al. J AAOPS. 2016; 20(3):220-5 Importance of good nutrition Formula vs. Breast Milk Human milk feeding substantially decreases risk of ROP The higher percentage the better Exclusive human milk may lower risk of severe ROP by as much as 90% Zhou J, et al. Pediatrics. 2015;136(6):e Ginovart G, et al. J Maternal Fetal Neonatal Med. 2016;29(23):

3 Other Potential Risk Factors Classification of ROP Unstable hospital course Intraventricular hemorrhage Pneumothorax Sepsis Chronic lung disease (Light exposure not a risk factor) Zone Stage Dilated, tortuous blood vessels ( PLUS disease) Three Zones of ROP Stages Zone I: 60 degrees centered on the optic nerve (worst prognosis) Zone II: To the nasal ora serrata Zone III: Temporal crescent (best prognosis) Stage Number Characteristic 1 Demarcation line 2 Ridge 3 Neovascularization 4 Partial Retinal Detachment 5 Total Retinal Detachment Higher stage indicates greater severity Stage 0 = immature retina without retinopathy 3

4 Stage 1 Stage 2 Distinct line An elevated ridge Stage 3 Stage 4 Neovascularization Partial retinal detachment Goal #1: Prevent this! 4

Total retinal detachment Goal #2: PREVENT THIS!

disease Plus Disease Who To Examine When To Examine 30 weeks or less birth EGA Less

EGA Every 1-3 weeks until retina is mature Pediatrics. 2006;117:572-576 Pediatrics.

5 Total retinal detachment Goal #2: PREVENT THIS! Stage 5 Dilated retinal venules Tortuous retinal arterioles Indicates more severe disease Plus Disease Who To Examine When To Examine 30 weeks or less birth EGA Less than1500 grams Extend criteria if severely ill 4-6 weeks after birth or weeks EGA Every 1-3 weeks until retina is mature Pediatrics. 2006;117: Pediatrics. 2006;118(3):errata Need for treatment 37 weeks - average age to reach threshold 90% reach threshold weeks EGA 5

6 When to Stop Long-Term Risks 1. Full vascularization (Mature) 2. Zone III is reached with no previous ROP 3. EGA of weeks and no severe ROP 4. ROP regressed Rules (Except #1) don t apply with Avastin Tx Late recurrence possible Follow until mature; may be many months Mild or no ROP Higher risk of strabismus and refractive errors F/U in 6 months Treated ROP High risk of high myopia with laser Geloneck MM, et al. JAMA Ophthalmol. 2014;132(11): High risk of strabismus ETROP Group. JAAPOS. 2011;15(6): Regular f/u by pediatric ophthalmologist Historical Guideline Threshold Disease Current Treatment Recs Based on ETROP Study Threshold Stage 3 (neovascularization) in Zone 1 or 2 at least 5 contiguous or 8 non-contiguous clock hours Plus disease Untreated threshold ROP progresses to retinal detachment in 50% of cases Cryotherapy used at time of this study Type 1 ROP Zone II Stage 2 or Stage 3 with Plus disease Zone I Stage 1 or Stage 2 with Plus disease Stage 3 with or without Plus disease (ETROP Group. Arch Ophthalmol. 2003;121(12): ) 6

(Off-label) BEAT-ROP study (Mintz-Hittner HA, et al. N Eng J Med.

7 ROP Laser Treatment ROP Laser Treatment ROP LaserTreatment Risks Cataract Anterior ischemia Progression in spite of treatment High myopia Loss of peripheral vision Bevacizumab (Avastin) Intravitreal injection (Off-label) BEAT-ROP study (Mintz-Hittner HA, et al. N Eng J Med. 2011;364(7): ) Recurrence equal to laser for Zone II Recurrence less than laser for Zone I Outcome measure was recurrence at 54 weeks PMA 7

8 Avastin May recur much later than with laser Mean 16 ( + 4.6) wks for Avastin Mean 6.2 (+ 5.7) wks for laser Study too small to assess safety Neurodevelopmental problems? Morin J, et al. Pediatrics. 2016;137(4) Counseling Parents Serious disease but good treatment options Severe vision loss (worse than 20/200) is uncommon Treatment works Over 95% success rate here Breast milk may lower risk by 90% Counseling Parents Hope even if bad outcome Services for visually impaired and other support services Let them know they are not alone Happy and successful people with low vision Research hopes 8

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

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