Overview of retinopathy of prematurity

1. RETINOPATHY OF
PREMATURITY
DR KM PARAKRAMA
REGISTRAR IN
PAEDIATRICS
NICU THK

2. INTRODUCTION
• ABNORMAL RETINAL BLOOD VESSEL DEVELOPMENT,
• MAY PROGRESS TO BLINDNESS
• ACUTE ROP DEVELOPS APPROXIMATELY 6–12 WEEKS POSTNATALLY.
• ‘WINDOW’ FOR TREATMENT IS NARROW,

3. • FIRST DESCRIBED IN 1942.
• EPIDEMIC OF BLINDNESS DUE TO ROP OCCURRED DURING THE 1940S AND
EARLY 1950S
• CAUSED BY THE USE OF UNRESTRICTED OXYGEN
• SECOND ‘EPIDEMIC’ OF ROP EMERGED DURING THE 1970S
• IMPROVED SURVIVAL OF VERY-LOW-BIRTHWEIGHT INFANTS

4. RETINAL BLOOD VESSEL DEVELOPMENT
• DEVELOP FROM CORDS OF MESENCHYMAL SPINDLE-SHAPED CELLS
• GROW OUT FROM THE OPTIC DISC,
• AT 15 WEEKS’ GESTATION
• DEVELOPMENT OF RETINAL BLOOD VESSELS IS DEPENDENT ON ANGIOGENESIS.
• PHYSIOLOGICAL HYPOXIA IN TISSUES ANTERIOR TO THE DEVELOPING BLOOD
• VESSELS LEADS TO HYPOXIA-INDUCIBLE FACTOR (HIF)-
• VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) BY GLIAL CELLS

5. • NASAL ORA SERRATA IS VASCULARISED BY ABOUT 34–36 WEEKS’ GESTATION
• TEMPORAL ORA SERRATA BY 36–40 WEEKS’ GESTATION

6. INTERNATIONAL CLASSIFICATION OF ROP
• RETINAL ZONES-
• EVIDENT AT THE JUNCTION OF VASCULARISED AND AVASCULAR RETINA.
• ZONE 1 RETINA IS DEFINED AS A CIRCLE,
• CENTRED ON THE CENTRE OF THE OPTIC DISC,
• WITH A RADIUS OF TWICE THE DISTANCE FROM THE OPTIC DISC TO THE CENTRE
OF THE MACULA
• ROP IN THIS ZONE PROGRESSES IN AN ESPECIALLY AGGRESSIVE MANNER

7. • ZONE 2 RETINA IS DEFINED AS THE CIRCLE OF RETINA, CENTRED ON THE
CENTRE OF THE OPTIC DISC THAT LIES ANTERIOR TO ZONE 1,
• AS FAR ANTERIORLY AS THE NASAL ORA SERRATA
• NASAL ORA SERRATA IS CLOSER TO THE OPTIC DISC THAN THE TEMPORAL ORA
SERRATA,
• A PERIPHERAL CRESCENT OF RETINA LIES ANTERIOR TO ZONE 2 ON THE
TEMPORAL SIDE OF THE RETINA,
• THIS IS TERMED ZONE 3 RETINA.
• ROP CONFINED TO ZONE 3 CARRIES A GOOD PROGNOSIS.

13. STAGES OF ROP
• APPEARANCE OF ACUTE ROP DISEASE AT THE JUNCTION OF VASCULARISED AND
AVASCULAR RETINA IS DESCRIBED IN STAGES
• STAGE 1 ROP A FLAT LINE DELINEATES THE JUNCTION OF VASCULARISED AND
AVASCULAR RETINA
• STAGE 2 ROP REFERS TO THE DEVELOPMENT OF AN ELEVATED RIDGE OF TISSUE
• STAGE 3 ROP, EXTRA RETINAL ANGIOGENESIS IS PRESENT
• MORE SEVERE

14. • POTENTIALLY POOR PROGNOSIS IF NOT TREATED.
• ABNORMAL EXTRA RETINAL BLOOD VESSELS MAY PROLIFERATE FURTHER,
• ASSOCIATED GLIAL TISSUE MAY LATER CONTRACT.
• – TRACTION RETINAL DETACHMENT STAGE 4 ROP.
• RETINA MAY BECOME COMPLETELY DETACHED – STAGE 5 ROP
• CAUSES COMPLETE, UNTREATABLE BLINDNESS.
• PLUS DISEASE
• ABNORMALITIES OF THE POSTERIOR RETINAL BLOOD VESSELS, AND THE IRIS
BLOOD VESSELS
• BLOOD VESSELS BECOME DILATED AND TORTUOUS.
• IN PART DUE TO HIGH LEVELS OF VEGF IN THE VITREOUS.

15. • ITS PRESENCE IS THE MAIN DETERMINANT OF THE NEED FOR INTERVENTIONAL
THERAPY
• STAGE 1 ROP.

22. PATHOGENESIS
• PREMATURE BIRTH INTERRUPTS NORMAL RETINAL BLOOD VESSEL
DEVELOPMENT.
• O2 REDUCES THE PHYSIOLOGICAL HYPOXIA DRIVE OF NORMAL RETINAL
ANGIOGENESIS.
• REDUCED HIF-CONTROLLED PRODUCTION OF VEGF
• REDUCED ENDOTHELIAL CELL PROLIFERATION AND MIGRATION
• REDUCED POSTNATAL IGF-1RESULT IN REDUCED RETINAL ENDOTHELIAL CELL
GROWTH
• INADEQUATELY VASCULARISED RETINA AT 6–10 WEEKS POSTNATALLY

23. • HIGH LEVELS OF TISSUE VEGF ARE PRODUCED AN ABNORMAL ANGIOGENESIS
RESPONSE OCCURS

24. RISK FACTORS FOR THE DEVELOPMENT OF
ROP
• EARLY GESTATION AND LOW BIRTHWEIGHT REMAIN THE STRONGEST RISK
FACTORS.
• O2
• OPTIMAL TREATMENT LEVELS HAVE NOT BEEN DEFINED.
• NUTRITION AND GROWTH
• SMALL-FOR-GESTATIONAL-AGE INFANTS ARE AT HIGHER RISK OF DEVELOPING
ROP
• REDUCED POSTNATAL GROWTH VELOCITY IS AN INDEPENDENT RISK FACTOR

25. • LOW LEVELS OF SERUM IGF-1 IN THE EARLY POSTNATAL PERIOD MAY PREDICT
THE DEVELOPMENT OF ROP.
• NUTRITIONAL THERAPIES THAT RESULT IN SATISFACTORY EARLY WEIGHT GAIN
MAY PROVE TO BE IMPORTANT
• BLOOD TRANSFUSIONS AND ERYTHROPOIETIN
• INCREASED TISSUE DELIVERY OF OXYGEN.

26. SCREENING

27. • EYE DROPS ARE INSTILLED 30 MINUTES PRIOR TO RETINAL EXAMINATION
• EYELID SPECULUM IS USED TO HOLD THE EYELIDS OPEN.
• EAMINATION IS PERFORMED WITH A BINOCULAR INDIRECT OPHTHALMOSCOPE,
OR A DIGITAL CAMERA THAT COMES INTO CONTACT WITH THE CORNEA
(RETCAM)

28. SRI LANKAN GUIDELINES
• IX-
• POG <32 WEEKS
• B.WT <1500G
• ANY SICK OR PRETERM NEONATE ON CLINICAL JUDGEMENT
• ANY BABY WITH CYANOTIC CHD

29. • TIME OF SCREENING-
• POG<28 WEEKS AT 2 WEEKS POSTNATAL AGE
• ALL OTHERS AT 4 WEEKS POSTNATAL AGE
• PLACE OF SCREENING-
• NICU/SCBU UNTIL DISCHARGED
• OUT-PATIENT AT EYE CLINIC
• DILATORS-
• ONE DROP TROPICAMIDE 0.4% PHENYLEPHRINE 2.5% COMBINED REPEATED
TWICE 10MIN APART

30. • IF NO ROP R/V EVERY 2 WEEKS UNTIL 42 WEEKS.

31. TREATMENT
• ROP IN ZONE 1 RETINA THAT HAS REACHED STAGE 3,
• OR IS ACCOMPANIED BY PLUS DISEASE, SHOULD BE TREATED.
• ROP IN ZONE 2 THAT HAS REACHED STAGE 2 OR 3,
• AND IS ACCOMPANIED BY PLUS DISEASE, SHOULD BE TREATED.
• PRESENCE OR ABSENCE OF PLUS DISEASE IS CRITICAL TO TREATMENT
DECISIONS.
• TREATMENT SHOULD BE PERFORMED WITHIN 48–72 HOURS.

32. • TREATMENT CURRENTLY CONSISTS OF LASER ABLATION OF PERIPHERAL
AVASCULAR, ISCHAEMIC RETINA.
• LASER IS DELIVERED TO THE RETINA ANTERIOR TO THE ROP RIDGE.
• RETINA IS ISCHAEMIC, AND ABLATION LEADS TO REDUCED VEGF PRODUCTION,
RESOLUTION OF ROP
• POTENTIAL COMPLICATIONS INCLUDE INTRAOCULAR BLEEDING, IRITIS AND
CATARACT DEVELOPMENT
• STEROID EYE DROPS AND PUPIL-DILATING EYE DROPS SHOULD BE GIVEN FOR 1
WEEK AFTER TREATMENT TO PREVENT IRITIS AND
• DEVELOPMENT OF ADHESIONS BETWEEN THE LENS AND IRIS.
• VITREORETINAL SURGERY MAY THEN BECOME NECESSARY IN A MINORIRITY.

34. • INTRAVITREAL BEVACIZUMAB/RANIBIZUMAB, WHEN USED AS MONOTHERAPY,
REDUCES THE RISK OF REFRACTIVE ERRORS DURING CHILDHOOD
• DOES NOT REDUCE THE RISK OF RETINAL DETACHMENT OR RECURRENCE OF
ROP IN INFANTS WITH TYPE 1 ROP
• MIGHT REDUCE THE RISK OF RECURRENCE OF ROP IN INFANTS WITH ZONE I ROP
• POTENTIALLY RESULT IN HIGHER RISK OF RECURRENCE REQUIRING
RETREATMENT IN THOSE WITH ZONE II ROP
• CONCLUSION
• FURTHER STUDIES ARE NEEDED TO EVALUATE THE EFFECT OF ANTI‐VEGF
AGENTS ON STRUCTURAL AND FUNCTIONAL OUTCOMES IN CHILDHOOD AND
DELAYED SYSTEMIC EFFECTS INCLUDING ADVERSE NEURODEVELOPMENTAL
OUTCOMES.

35. •THANK YOU!