retinopathy of prematurity diagnosis and treatment

1. Dr. Lakshmi.K.S
Moderator: Dr. Devika.P
1

2. 25/9/2013
On Examination Right Left
(Torchlight)
 Eye Lids N N
 External structures N N
 Eye malalignment - -
 Nystagmus - -
 Sclera yellowish
yellowish
 Cornea clear clear
 Iris N N
 Lens clear clear
2

3. Direct ophthalmoscope R
L
 Red reflex + +
Indirect ophthalmoscope
 Dilated fundus examination
3

4. Dilated fundus on 25/9/2013
4

5. 5

6. Dilated fundus on 3/10/13
6

7. 7

8. Dilated fundus on 6/10/13(post
laser left eye)
8

9. 9

10. Rx:
 Tobramycin Dexamethasone Eye
Drops
QID * 1 week
 Review after 3 days
10

11. Dilated Fundus on 10/10/13
11
Laser Marks seen, plus regressedAll Zones Vascularized

12. Discussion: Diagnosis
 Early diagnosis and secondary prevention
of visual loss must
 International Classification of ROP
(ICROP) is used:
• For documentation of the deterioration or
regression of ROP
• For therapeutic interventions
*The International Classification of Retinopathy of Prematurity revisited. Arch
Ophthalmol
2005;123:991-9
12

13. CLASSIFICATION- ICROP
 ZONE/ LOCATION
 SEVERITY
 EXTENT
 PLUS DISEASE
 PREPLUS DISEASE
13

14. Zone
1. Location
 Zone I
Circle with optic nerve at
center and a radius of
twice the distance from
optic nerve to macula
 Zone II
A concentric circle From
edge of Zone I to the
nasal ora serrata
 Zone III
Lateral most crescent
shaped area from Zone
II to ora-serrata
temporally
14

15. ZONES
15

16. SEVERITY
16

17. Stage 1
 Presence of thin
white demarcation
line
 separating the
vascular from
avascular retina
17

18. Stage 2
 The line becomes
prominent because
of lifting of retina to
form a ridge having
height and width
18

19. Stage 3
 Presence of extra
retinal fibro-
vascular
proliferation with
abnormal vessels
and
fibrous tissue arising
from the ridge and
extending into
vitreous
19

20. Stage 4
 Partial retinal detachment; not involving
macula (4A) or involving macula (4B)
20

21. 21
STAGE IV a STAGE
IV b

22. Stage 5
 Complete retinal detachment
22
Open open, open narrow, narrow open, narrow narrow

23. Extent
Extent of involvement of the retina
expressed as clock hours (30 degree
sectors)
 8+ cumulative clock hour sectors
 5+ continuous clock hour sectors
24

24. Plus disease
 Presence of
dilatation and
tortuosity of posterior
retinal vessels of at
least 2 quadrants.
 Associated with
vitreous
haze, pupillary
rigidity
 Arises gradually or
very rapidly.
 Due to AV shunting
mainly in ridge tissue
 Severity indicator
25

25.  Often associated with
-Iris vessel
engorgement
-Miosis
-Resistance to dilating
medications
-Vitreous haze
-Tunica vasculosa
lentis
26

26. Pre-plus disease
 Vascular
abnormalities of the
posterior pole that
are insufficient for
the diagnosis of plus
disease but that
demonstrate more
arterial tortuosity and
more venous
dilatation than
normal
 serves as a warning
27

27. CLINICALLY SIGNIFICANT
TERMS
 Threshold ROP: CRYO ROP study
Zone I stage III with Plus
Zone II Stage III with Plus
( 5 contigous or total 8 clock
hours)
*Cryotherapy for Retinopathy of Prematurity Cooperative G. Multicenter Trial
of Cryotherapy for Retinopathy of Prematurity: preliminary results. Arch
28

28.  Prethreshold ROP: ETROP study*
High risk Prethreshold
Zone I , any stage with plus
Zone 1, Stage 3 without plus
Zone II Stage 2 and 3 with plus
Perepheral retinal ablation indicated
*Early Treatment For Retinopathy Of Prematurity Cooperative G. Revised
indications for the treatment of retinopathy of prematurity: results of the
early treatment for retinopathy of prematurity randomized trial. Arch
Ophthalmol 2003;121:1684-94
29

29. AP-ROP: aggressive posterior
ROP
-Earlier known as
‘RUSH Disease’
-posterior location,
-rapidly evolving
preplus and plus
disease
neovascularization that
may be subtle or even
intraretinal in nature.
-Progress to stage IV &
V in 2-3 weeks without
passing through
characteristic stages II
and III
- requires laser
treatment more than
once
30

30. Which babies should be
screened?
 Babies with birth weight <1500 g
 Babies born at ≤ 32 weeks of gestation
 Selected preterm infants with a birth weight
between 1500 and 2000 g or gestational age
of more than 32 weeks with sickness like
 need of cardiorespiratory support,
 prolonged oxygen therapy,
 apnea of prematurity,
 anemia needing blood transfusion
 neonatal sepsis
*Azad R, Chandra P, Patwardhan SD, Gupta A. Importance of the 'third criterion' for
retinopathy of prematurity screening in developing countries. J Pediatr Ophthalmol Strabismus
2009;46:332-4
31

31. When to screen?
 First
screening
examination
should be
carried out at
31 weeks of
gestation or 4
weeks of
age, whicheve
r is later
32
Gestational
age at birth
Postmenstrual
age (examination)
Chronological
age (examination)
22 31 9
23 31 8
24 31 7
25 31 6
26 31 5
27 31 4
28 32 4
29 33 4
30 34 4
31 35 4
32 36 4

32. Follow-up examinations
Findings that suggest further
examinations are not needed include:
 Zone III retinal vascularization attained
without previous Zone I or II ROP
 Full retinal vascularization
 Postmenstrual age of 45 weeks and
no prethreshold disease
 Regression of ROP
33

33. 2- to 3-week follow-up
 Immature vascularization: Zone II—no
ROP
 Stage 1 or 2 ROP: Zone III
 Regressing ROP: Zone III
34

34. 2-week follow-up
 Stage 1 ROP: Zone II
 Regressing ROP: Zone II
 Immature vascularization: Zone I—no
ROP
 Stage 2 ROP: Zone II
 Regressing ROP: Zone I
35
1-2-week follow-up

35. 1-week or less follow-up
 Stage 1 or 2 ROP: Zone I
 Stage 3 ROP: Zone II
36

36. Where to examine the baby?
 Neonates are best examined in the
neonatal unit itself under supervision
of attending pediatrician.
 ROP screening examinations can
have short-term effects on blood
pressure, heart rate and respiratory
function in the premature baby
*Sun X, Lemyre B, Barrowman N, O'Connor M. Pain management during eye examinations
for retinopathy of prematurity in preterm infants: a systematic review. Acta Paediatr 2009
37

37. How to dilate the pupils?
 One drop of Tropicamide 0.5% is
instilled every 10-15 minutes for 4
times starting 1 hour before the
scheduled time for examination.
 Phenylephrine 2.5%, one drop just
before examination.
38

38. Examination
 Instilling a topical anesthetic drop like
Proparacaine 0.5%
 Wire speculum is inserted to keep the
eye-lids apart
 Indirect ophthalmoscopy using 20 D
or 28/30 D lens
Anterior segment: vasculosa
lentis, vessels on iris, pupillary
dilatation, lens opacities
Fundus examination-
zone, severity, extent, plus, preplus 39

39. Documentation
 Retinopathy of
Prematurity
Screening
Examination
Record Sheet
40

40. What precautions are taken
during examination?
 Administering oral sucrose just before
examination,
 Pretreatment of the eyes with a topical
proparacaine and swaddling the baby.
 Baby should not have been fed just
before examination to avoid vomiting and
aspiration.
 Hand washing should be done
 Asepsis maintained
*Sun X, Lemyre B, Barrowman N, O'Connor M. Pain management during eye examinations
for retinopathy of prematurity in preterm infants: a systematic review. Acta Paediatr 2009
41

41. Use of wide-field digital camera
(RetCam) for screening
 Alternative to indirect ophthalmoscopy for
screening
 130 degree field of view of retina seen
 Useful adjunct to conventional bedside ROP
screening by indirect ophthalmoscopy to
document the stage.
 Useful for telemedicine purposes
 Trained certified graders could provide timely
and cost-effective input into ROP
management, identifying infants requiring on-
site examination or treatment
*Kemper AR, Wallace DK, Quinn GE. Systematic review of digital imaging screening
strategies for retinopathy of prematurity. Pediatrics 2008;122:825-30.
42

42. 43

43. Future use of retcam
 Wallace et al
 Chang et al
 Efforts made to quantify diagnosis of retinal
vessel dilatation and tortuosity more
consistently and accurately in an objective
way
 Johnson et al- vessel map software uses
retcam images to quantify retinal vessel
diameter
 Wallace et al- ROP tool software to quantify
retinal vessel tortuosity
 These studies suggest digital imaging may
offer an objective way to diagnose disease
and might be the only way used in near future
44
Inter observer variation exists in the
diagnosis of plus and pre plus disease

44. TREATMENT
For initial vasoproliferative disease
 PEREPHERAL RETINAL ABLATION
◦ Cryotherapy
◦ LASER
• Intravitreal injection of bevacizumab
For late cicatricial manifestations
 VITRECTOMY- for retinal detachment
◦ LENS SPARING
◦ With LENSECTOMY
 SCLERAL BUCKLING- for retinal detachment
45

45. Cryo ROP study*
 Treatment given for a threshold of
severity of stage 3 involving 5
continuous clock hours or 8
cumulative clock hours in zone 1 or
11.
*Cryotherapy for Retinopathy of Prematurity Cooperative G.
Multicenter Trial of Cryotherapy for Retinopathy of Prematurity:
preliminary results. Arch Ophthalmol. 1988;106:471–9
46

46. Cryotherapy
 Under GA
 Distance from ridge to limbus noted
 Applied to the anterior avascular area wherever ridge
is present
 Ridge avoided
 SPOTS – Preferrably Transconjunctival
Contiguous
15 – 30
End point – creamy white
Copious irrigation
*Cryotherapy for Retinopathy of Prematurity Cooperative G. Multicenter Trial
of Cryotherapy for Retinopathy of Prematurity: preliminary results. Arch
Ophthalmol. 1988;106:471–9
47

47. Advantage of Diode LASER
over Cryotherapy
 Easier to perform and better tolerated by the
infants and equally efficacious
 Less pain and bradycardia during the
procedure
 Sedation without endotracheal intubation
works well in most cases
 More ease of reaching posterior retina i.e.
zone 1
 Less associated with post op lid swelling and
chemosis when compared with cryotherapy
 Exudative retinal detachment rarer when
compared to cryotherapy
 Less incidence of myopia 48

48. Early Treatment of Retinopathy
of Prematurity (ETROP) trial
Two new terminologies have been suggested
Type 1 ROP: prethreshold
 Zone I, any stage ROP with plus disease
 Zone I, stage 3 ROP with or without plus
disease
 Zone II, stage 2 or 3 ROP with plus disease
Peripheral retinal ablation should be carried out
for all cases with type 1 ROP
Type 2 ROP: prethreshold
 Zone I, stage 1 or 2 ROP without plus
disease
 Zone II, stage 3 ROP without plus disease
continued serial examinations are advised for
type 2 ROP 49
*Early Treatment For Retinopathy Of Prematurity Cooperative G. Revised indications for the
treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity
randomized trial. Arch Ophthalmol 2003;121:1684-94

49. Preparation for laser ablative
therapy
 Take consent
 Ensure good pupillary dilatation
 Nil by mouth 3 h prior to procedure
 Start on intravenous fluids
 Put on vital sign monitor/pulse
oximeter
 Warmer for maintaining temperature
 Arrange equipment and check
functioning thereof
50

50.  Intubation equipment
 Endotracheal tubes No. 2.5, 3, 3.5
 Resuscitation bag & face masks
 Oxygen delivery system
 Syringes
 Infusion pumps
 Ventilator
 Arrange drugs, fill syringes in advance
with drugs in appropriate dilution and
label them :
morphine, midazolam, normal saline
10% dextrose, adrenalin
51

51.  Topical anesthesia
 Adequate sedation and analgesia
 Can be done in OT or NICU with a
pediatrician standby
52

52.  Delivered through INDIRECT OPHTHALMOSCOPE + 20D
 Ridge Avoided
 SPOTS
Size =100 microns
Half burn width apart
End point – grade II gray burn
53

53. 54

54. Monitoring after laser therapy
 First examination should take place 5-7
days after treatment
 Should be continued at least weekly for
signs of decreasing activity and
regression.
 Re-treatment should be performed
usually 10-14 days after initial treatment
when there has been a failure of the
ROP to regress or if any untreated/skip
areas of avascularity seen
 All babies with stage 3 ROP in which
ROP resolved spontaneously, and
babies requiring treatment of
ROP, require ophthalmic review at least 55

55. Post-operative care
 If condition permits, oral feeds can be
started shortly after the procedure.
 Premature babies, especially those with
chronic lung disease may have increase
or re-appearance of apneic episodes or
an increase in oxygen requirement.
Therefore they should be carefully
monitored for 48-72 hours after the
procedure.
 Antibiotic steroid drops should be
instilled 6-8 hourly for 2-3 days.
56

56. After LASER treatment
 zone 2 ROP
◦ generally regresses after a single treatment session.
 APROP*
◦ may regresses but can reactivate with return of plus
disease
◦ progressive posterior hyaloidal contraction, and
progression to tractional posterior retinal detachment
◦ Post-treatment vigilance is necessary
Treatment in 2 Steps
Ist – upto Flat Neovascular Fronds
IInd – after regression of Fronds
*Vinekar A, Trese MT, Capone A., Jr Evolution of retinal detachment in posterior
retinopathy of prematurity: impact on treatment approach. Am J
Ophthalmol. 2008;145(3):548–55
57

57. Intravitreal Avastin injections
 Non FDA approved
 Bevacizumab (Avastin) is a monoclonal
antibody fragment that binds all isoforms
of VEGF.
 Indications:
-failure of retinal ablation
-hazy media due to vitreous hemorrhage
pre laser or intra laser procedure.
-Undilating Pupil
-very severe proliferative vitreoretinopathy
58

58.  Several studies have reported cases of
ROP treated with intravitreal
bevacizumab with good reports.
 However, there has been a report of
adverse contraction of proliferative
membranes after bevacizumab injection
leading to retinal detachment
 Currently underway in the United States
is a multicenter prospective phase I
safety trial of intravitreal bevacizumab for
zone I ROP.
59

59. Treatment of stage 4 and 5
ROP
 Despite timely and thorough laser as
performed in the ETROP study, almost 1 in
10 infants treated with laser for ROP will
develop unfavorable structural outcomes like
retinal detachment
 The key to successful outcome is to operate
after the neovascular activity and plus
disease have completely or almost
completely resolved
 The operative technique most commonly
utilized for tractional stage 4 ROP is 2-
port, lens-sparing vitrectomy (LSV) with or
without scleral buckling
60

60. VITRECTOMY
Necessary in advanced cases
Lensectomy avoided
Peeling of membranes
Relieve of traction
No attempt to drain Sub Retinal Fluid
AIM : Ambulatory vision i.e. being able to
see objects and move around a room
without stumbling or bumping into
obstacles.
61

61. Adjuncts to vitrectomy
1. use of intravitreal triamcinolone (2.0
mg/0.05 ml) injected at the end of the
vitrectomy procedure*
 Drug has the ability to cause resolution
of plus disease and involution of
neovascularization
2. use of autologous plasmin for stage 5
ROP**
 Plasmin is known to cleave laminin and
fibronectin and can assist in separating
cortical vitreous from the surface of the
retina
62
*Lakhanpal RR, Fortun JA, Chan-Kai B, Holz ER. Lensectomy and vitrectomy with and without intravitreal
triamcinolone acetonide for vascularly active stage 5 retinal detachments in retinopathy of
prematurity. Retina. 2006;26(7):736–40
**Tsukahara Y, Honda S, Imai H, et al. Autologous plasmin-assisted vitrectomy for stage 5 retinopathy of
prematurity: a preliminary trial. Am J Ophthalmol. 2007;144(1):139–41

62. Scleral buckling
Can be done along with
vitrectomy
Under GA
-Peritomy
-2.5 mm encircling band
passed beneath 4 Recti
-One anchoring
mattress suture applied
in all quadrants
-Removal after 3-6
months
63

63. Take home message
 Preventive strategies
 Early diagnosis by effective screening
program
 Proper follow up
 Early treatment to prevent stage 4 and
5 ROP

64. References
 Yanoff & Duker: Ophthalmology, 3rd
ed.
 Retinopathy of prematurity, AIIMS-
NICU protocols 2010
 Jack J Kanski and Brad
Bowling, clinical ophthalmology
 Surgical Management of Retinopathy
of Prematurity; G. Baker Hubbard, III;
Curr Opin Ophthalmol. 2008
September; 19(5): 384–390. 69

65. 70