retinopathy of prematurity

1. Retinopathy Of PrematurityRetinopathy Of Prematurity
Dr. samarth mishraDr. samarth mishra

2. IntroductionIntroduction
 Retinopathy of prematurity (ROP) was formerly knownRetinopathy of prematurity (ROP) was formerly known
as retrolental fibroplasia (RLF).as retrolental fibroplasia (RLF).
 It is a developmental proliferative retinopathy thatIt is a developmental proliferative retinopathy that
occurs in the premature infants due to incompleteoccurs in the premature infants due to incomplete
vasculogenesis of the retina at the time of birth.vasculogenesis of the retina at the time of birth.
 ““Vision 2020 program”- important cause of blindness inVision 2020 program”- important cause of blindness in
children.children.

3. IncidenceIncidence
 Overall incidence: 16-17% for all premature infants.Overall incidence: 16-17% for all premature infants.
 68% ROP in BW < 1250 g68% ROP in BW < 1250 g
 98% among those having BW < 750 g98% among those having BW < 750 g

4. Risk FactorsRisk Factors

5. PathogenesisPathogenesis
Normal Retinal Vascular DevelopmentNormal Retinal Vascular Development
Nasal side Temporal side
8 months

7. Stage 1 Vasculogenesis
Formation of primitive Vascular tube
Stage 2 Angiogenesis

8. Newly develop hypoxic
Neural retina
Secreted VEGF

9. From birth to postmenstrual age
30-32 wks
Relatively hyperoxic condition
(supplemental O2) suppresses VEGF
mRNA & normal VEGF driven growth
Apoptosis of vascular endothelial cells &
Vaso-obliteration
Begins around 32-34 weeks
Post-menstrual age
Nonvascularized retina becomes
Metabolically active due to continued
Development of retinal neural cells
Hypoxia which stimulate over
Production of VEGF

10. Increased level of VEGF with IGF
uncontrolled neovascularization
Vascular growth into vitreous & finally RD

12. Classification of ROPClassification of ROP
International Classification of ROPInternational Classification of ROP –– 19841984
1.1.ZZoneone
2.2.ExtentExtent
3.3.SStagetage
4.4.PPlus diseaselus disease

13. Zone:Zone:
Zone 1:Zone 1: circle centered on disc with radius = 2 x “circle centered on disc with radius = 2 x “disc to foveadisc to fovea””
distancedistance
Zone 2:Zone 2: circle centered on disc with radius = “disc to nasal ora”circle centered on disc with radius = “disc to nasal ora”
distance (nasal ora to temporal equator) but outside Zone 1distance (nasal ora to temporal equator) but outside Zone 1
Zone 3Zone 3: remaining temporal crescent beyond Zone 2: remaining temporal crescent beyond Zone 2
Extent:Extent:
 Divide the retinal surface into 12 segments (clock hours).Divide the retinal surface into 12 segments (clock hours).
Stage of retinopathy can vary among segments.Stage of retinopathy can vary among segments.

15. Stages ( 1-5)Stages ( 1-5)
 Stage 1:Stage 1:
 Demarcation lineDemarcation line -a flat, thin, whitish, clear-cut-a flat, thin, whitish, clear-cut
demarcation between vascularised and avascular retina.demarcation between vascularised and avascular retina.

16.  Stage 2:Stage 2:
 Elevated ridgeElevated ridge -- demarcation line has ”3D” appearnce &demarcation line has ”3D” appearnce &
extends anteriorly from the retinal plane as a ridge into theextends anteriorly from the retinal plane as a ridge into the
vitreous.vitreous.

17.  Stage 3:Stage 3:
 NeovascularisationNeovascularisation - Extraretinal fibrovascular tissue begins- Extraretinal fibrovascular tissue begins
to grow on the top of the ridge or posterior to the ridge andto grow on the top of the ridge or posterior to the ridge and
extends into the vitreous.extends into the vitreous.
 ““Pop-corn lesion”Pop-corn lesion”

18.  Stage 4:Stage 4: Partial RDPartial RD
1.1. 4A: Extra-Foveal4A: Extra-Foveal
2.2. 4B: Foveal4B: Foveal
 Stage 5:Stage 5: Total RDTotal RD
1.1. Open-Open funnelOpen-Open funnel
2.2. Open-Narrow funnelOpen-Narrow funnel
3.3. Narrow-open funnelNarrow-open funnel
4.4. Narrow-Narrow funnelNarrow-Narrow funnel

19. Plus DiseasePlus Disease
 Venous dilatation or arteriolar tortuosity in at least two quadrantsVenous dilatation or arteriolar tortuosity in at least two quadrants
 poor pupil dilatationpoor pupil dilatation
 vitreous hazevitreous haze
 vascular engorgement of the iris with extension onto anterior lens surfacevascular engorgement of the iris with extension onto anterior lens surface
k/a tunica vasculosa lentis.k/a tunica vasculosa lentis.
 HHallmark of rapidly progressive ROP & noted by adding aallmark of rapidly progressive ROP & noted by adding a ““++”” sign after thesign after the
number of ROP stage.number of ROP stage.

20. ICROP Revisited 2005ICROP Revisited 2005
1.1. Aggressive posterior ROP (APROP)Aggressive posterior ROP (APROP)
2.2. Pre-plus DiseasePre-plus Disease
3.3. Clinical pearl for clarification of the extent of Zone 1Clinical pearl for clarification of the extent of Zone 1

21. Aggressive posterior ROP (APROP)Aggressive posterior ROP (APROP)
 Ill defined ROP with plus Ds in Zone 1 or sometimes posteriorIll defined ROP with plus Ds in Zone 1 or sometimes posterior
Zone 2Zone 2
 Posterior pole vessels show increased dilatation & tortuosityPosterior pole vessels show increased dilatation & tortuosity
in all 4 quadrants out of proportion to peripheryin all 4 quadrants out of proportion to periphery
 Direct AV shuntingDirect AV shunting
 Doesn’t progress through classic stages 1 to 3Doesn’t progress through classic stages 1 to 3
 Neovascularization may be flat, featurelessNeovascularization may be flat, featureless
 Typically extends circumferentially & is often accompanied byTypically extends circumferentially & is often accompanied by
a circumferential vessel.a circumferential vessel.
 Observed in smallest premature infants & requires promptObserved in smallest premature infants & requires prompt
laser T/tlaser T/t
 Previously called “Rush Ds”.Previously called “Rush Ds”.

22. APROPAPROP
zone 1
zone 2
shunt vessel
avascular retina

23. Pre-Plus DsPre-Plus Ds
 More arterial tortuosity & more venous dilation ofMore arterial tortuosity & more venous dilation of
posterior pole that are insufficient for Dx of Plus Ds.posterior pole that are insufficient for Dx of Plus Ds.
 Dx of Pre-plus Ds has prognostic value.Dx of Pre-plus Ds has prognostic value.

24. Clarification of the extent of Zone 1Clarification of the extent of Zone 1

25. Spontaneously regressed ROPSpontaneously regressed ROP
 Peripheral changes:Peripheral changes:
1.1. Telangiectatic retinal vesselsTelangiectatic retinal vessels
2.2. Pigmentary changesPigmentary changes
3.3. Lattice like degenerationLattice like degeneration
4.4. Vitreous membraneVitreous membrane
5.5. Localized tractional detachmentLocalized tractional detachment
 Posterior pole changes:Posterior pole changes:
1.1. Tortuous vesselsTortuous vessels
2.2. Narrow temporal arcadeNarrow temporal arcade
3.3. Disk dragDisk drag
4.4. Macular heterotopiaMacular heterotopia
5.5. Falciform foldFalciform fold
regressed stage

26. Differential DiagnosisDifferential Diagnosis

27. SCREENING GUIDELINESSCREENING GUIDELINES
Recommendations based on review of data from the CRYO-Recommendations based on review of data from the CRYO-
ROP and LIGHT-ROP studiesROP and LIGHT-ROP studies
 Screening methodScreening method
1.1. IDO with a 20 or 28 D lens.IDO with a 20 or 28 D lens.
2.2. Eye speculumEye speculum
3.3. Scleral indenterScleral indenter
 Whom to screenWhom to screen
1.1. BW < 1500 g orBW < 1500 g or
2.2. Gestational age < 30 weeks orGestational age < 30 weeks or
3.3. Infants with an unstable clinical course who are at high riskInfants with an unstable clinical course who are at high risk
(as determined by paediatrician)(as determined by paediatrician)

29. In Indian ScenarioIn Indian Scenario
 BW < 2000 gBW < 2000 g
 GA < 34-35 weeksGA < 34-35 weeks
 Initial screening recommended between 20-30 days ofInitial screening recommended between 20-30 days of
life.life.
 Early screening (i.e. < 20 days of life) is stronglyEarly screening (i.e. < 20 days of life) is strongly
recommended for babies < 30 weeks of GA.recommended for babies < 30 weeks of GA.

30. Indications of treatmentIndications of treatment
 CRYO-ROP StudyCRYO-ROP Study:: Treat “Threshold disease” of ROPTreat “Threshold disease” of ROP
1.1. Stage 3 ROP in zone 1, or zone 2Stage 3 ROP in zone 1, or zone 2
2.2. Involving 5 or more contiguous or 8 cumulative clockInvolving 5 or more contiguous or 8 cumulative clock
hourshours
3.3. presence of plus diseasepresence of plus disease
 With threshold disease there is a 50% predicted risk ofWith threshold disease there is a 50% predicted risk of
blindness.blindness.

31. 8 Noncontiguous or 5 Contiguous Clockhours of NV (Stage 3)8 Noncontiguous or 5 Contiguous Clockhours of NV (Stage 3)

32. ETROP studyETROP study
 Type 1/ High risk Pre-threshold ROP:Type 1/ High risk Pre-threshold ROP:
1.1. Zone 1 ROP, any stage with plus diseaseZone 1 ROP, any stage with plus disease
2.2. Zone 1 ROP, stage 3 without plus disease orZone 1 ROP, stage 3 without plus disease or
3.3. Zone 2 ROP, stage 2 or 3 with plus diseaseZone 2 ROP, stage 2 or 3 with plus disease
 Type 2/ Low risk Pre-threshold ROP:Type 2/ Low risk Pre-threshold ROP:
1.1. Zone 1, stage 1 or 2 without plus DsZone 1, stage 1 or 2 without plus Ds
2.2. Zone 2, stage 3 without plus DsZone 2, stage 3 without plus Ds
 Type 1 ROP should be treated promptly within 72 hrs of DxType 1 ROP should be treated promptly within 72 hrs of Dx

33. Treatment ModalityTreatment Modality
 Principle:Principle: To remove the stimulus (VEGF) for growth ofTo remove the stimulus (VEGF) for growth of
new blood vessels by ablating the peripheral avascularnew blood vessels by ablating the peripheral avascular
retina.retina.
1.1. CryotherapyCryotherapy
2.2. Laser photocoagulation – standard treatmentLaser photocoagulation – standard treatment
3.3. Surgical interventionsSurgical interventions
A.A. Scleral bucklingScleral buckling
B.B. VitrectomyVitrectomy

34. CryotherapyCryotherapy
Trans-scleral or TransconjunctivalTrans-scleral or Transconjunctival
Complication:Complication:
1.1.IOHIOH
2.2.Eyelid edemaEyelid edema
3.3.Conjunctival hematomaConjunctival hematoma
4.4.Conjuntival lacerationConjuntival laceration
5.5.BradycardiaBradycardia
6.6.Respiratory distressRespiratory distress

35. Laser PhotocoagulationLaser Photocoagulation
 less invasiveless invasive
 less traumatic to the eyeless traumatic to the eye
 causes less discomfort to the infantcauses less discomfort to the infant
 Easy to apply in posteriorly located disease.Easy to apply in posteriorly located disease.
 Both Argon green and Diode red wavelengths laser can be deliveredBoth Argon green and Diode red wavelengths laser can be delivered
through an indirect ophthalmoscope.through an indirect ophthalmoscope.
 Aim:Aim: near-confluent ablation of peripheral avascular retinanear-confluent ablation of peripheral avascular retina with burnswith burns
spaced one half burn-width apart, from ora serrata upto the ridge for 360spaced one half burn-width apart, from ora serrata upto the ridge for 360
degree.degree.
 Complication: corneal burn, hazy, Iris burn, cataract, burns of tunicaComplication: corneal burn, hazy, Iris burn, cataract, burns of tunica
vasculosa lentis causing IOH.vasculosa lentis causing IOH.

36. Before laser therapy After laser therapy

37. SurgicalSurgical
 Scleral buckling or lens sparing vitrectomy are indicated forScleral buckling or lens sparing vitrectomy are indicated for
stage 4 ROPstage 4 ROP
 Lens sacrificing vitrectomy for stage 5 ROPLens sacrificing vitrectomy for stage 5 ROP

38. Current Trends in ROP TreatmentCurrent Trends in ROP Treatment

39. BEAT-ROP (Bevacizumab Eliminates the Angiogenic Threat inBEAT-ROP (Bevacizumab Eliminates the Angiogenic Threat in
ROP) 2011ROP) 2011
 RCT (150 infants, 300 eyes)RCT (150 infants, 300 eyes)
 SStudy:tudy: Stage 3, plus, Stage 3, plus, Zone 1 and posterior Zone 2Zone 1 and posterior Zone 2
 CCompare:ompare: Intravitreal Bevacizumab (Intravitreal Bevacizumab (0.625 mg / 0.025ml, 2.5 mm post0.625 mg / 0.025ml, 2.5 mm post
limbus)limbus) vs.vs. Peripheral Laser (ETROP)Peripheral Laser (ETROP)
 Results:Results:
1. Bevacizumab reduced recurrence of ROP1. Bevacizumab reduced recurrence of ROP
 Bevacizumab recurrence: 6 of 140 eyes (Bevacizumab recurrence: 6 of 140 eyes (4%4%))
 Laser recurrrence: 32 of 146 eyes (Laser recurrrence: 32 of 146 eyes (22%22%))
2. Bevacizumab benefit over laser in Zone 12. Bevacizumab benefit over laser in Zone 1
3. Bevacizumab allowed continued peripheral vascularization into3. Bevacizumab allowed continued peripheral vascularization into
avascular retinaavascular retina

41. Cons & Pros of Anti VEGFCons & Pros of Anti VEGF
Anti-VEGF agents are being used in ROP treatment asAnti-VEGF agents are being used in ROP treatment as
1. Monotherapy1. Monotherapy
Becoming less desirable if periphery not perfusedBecoming less desirable if periphery not perfused
Concern for late retinal detachmentsConcern for late retinal detachments
2. Adjunctive therapy with laser (or cryotherapy)2. Adjunctive therapy with laser (or cryotherapy)
3. Perioperative therapy to induce NV regression3. Perioperative therapy to induce NV regression
Dosing, schedule, and ROP recurrence patterns are still uncertainDosing, schedule, and ROP recurrence patterns are still uncertain
Retinal detachments after anti-VEGF have occurredRetinal detachments after anti-VEGF have occurred
Long term safety data still uncertainLong term safety data still uncertain
Extended follow up is required for anti-VEGF treated ROP eyes withExtended follow up is required for anti-VEGF treated ROP eyes with
incomplete vascularizationincomplete vascularization
Screening ~ every 1-2 weeksScreening ~ every 1-2 weeks

42.  Recombinant human erythropoietin (rhEPO) has beenRecombinant human erythropoietin (rhEPO) has been
tried.tried.

43. Long Term Complications of ROPLong Term Complications of ROP
 70% became myopic due to macular heterotopia (temporal70% became myopic due to macular heterotopia (temporal
macular drag) & straightened blood vessels.macular drag) & straightened blood vessels.
 Curvature myopiaCurvature myopia
 Astigmatism >2D, if uncorrected leads to amblyopia.Astigmatism >2D, if uncorrected leads to amblyopia.
 Strabismus 20.3%Strabismus 20.3%
 Late onset RD 25.6%Late onset RD 25.6%
 Cataract 83.7%Cataract 83.7%
 GlaucomaGlaucoma
 Exudative retinopathyExudative retinopathy
Retinal
Dragging and
Folds
Strabismus

44. AdvancesAdvances

45. Computer-assisted Quantification of Plus DsComputer-assisted Quantification of Plus Ds

46. TelescreeningTelescreening
Important in areas with limited access to ophthalmic careImportant in areas with limited access to ophthalmic care
Take the picture of immature fundus using RetCam by trainedTake the picture of immature fundus using RetCam by trained
nurse or technician.nurse or technician.
Multiple image telemedicine perform to determine the stagesMultiple image telemedicine perform to determine the stages
n early initiation of treatment n follow up.n early initiation of treatment n follow up.

47. ConclusionConclusion
 Ultimate prevention = prevent premature births.Ultimate prevention = prevent premature births.
 The role of VEGF and IGF-1 may lead to pharmacologicThe role of VEGF and IGF-1 may lead to pharmacologic
interventions in preventing progression.interventions in preventing progression.
 Evidence based data reshape our understanding of who toEvidence based data reshape our understanding of who to
screen and determines the critical timing of treatment.screen and determines the critical timing of treatment.
 Surgical intervention preserves vision in ROP-related retinalSurgical intervention preserves vision in ROP-related retinal
detachment esp. before macular detachment.detachment esp. before macular detachment.

48. THANK YOU….!THANK YOU….!