Retinopathy in elbw babies

1. Retinopathy of Prematurity
PRESENTED BY -ADITYA RAHANE
GUIDE-Dr. RIZWAN AHMED

4. NORMAL RETINAL
DEVELOPMENT

5. NORMAL RETINAL
DEVELOPMENT
• Sclera  Choroid  Retina
• Retinal layers: Nerve fibers, ganglion cells,
photoreceptors migrate from center of optic
disc to the periphery
• By 28 weeks: The photoreceptors migrate 80%
of the distance towards ora-serrata
• Before the retinal vessels develop the avascular
retina receives oxygen by diffusion from the
choroid vessels

6. NORMAL RETINAL
DEVELOPMENT
• 16 weeks  Retinal vessels arise from hyaloid vessels
at optic disc and begin to migrate outwards
• 36 weeks  Migration is complete on nasal side
• 40 weeks  Migration is complete on temporal
side

7. • ROP is fibro vascular proliferative disorder, that affects the developing
peripheral retinal vasculature of premature infants.
• ROP is unique in that it affects an immature , incompletely vascularised
retina.
• First described by Terry in 1942 as retrolental fibroplasia.
• Approximately 65% of infants with a birth weight <1,250gm and
80% of those with a birth weight <1,000gm will develop some
degree of ROP.
DEFINATION

8. RISK FACTOR
Among the crucial risk factors of ROP are
1. Low Birth weight
2. Gestational age
3. Number of days oxygen Administered.
4. Other risk factors Include
• RDS
• Sepsis
• IVH
• IUGR

9. • Vit E deficiency
• Anaemia
• Blood transfusion
• Seizures
• High ambient light
• Hypoxia
• Acidosis
• Ventilatory support
RISK FACTOR

10. PATHOGENESIS
Stage I
• Hyperoxia mediated
vasocontriction
Stage I
• Vasoconstriction and decreased blood flow to
developing retina
• Arrest of vascular development
Stage I
• Hyperoxia causes down regulation of VEGF
and EPO that is essential for normal
development of retinal vessels
ACUTE STAGE-hyperoxia mediated
vasocessation

11. PATHOGENESIS
Stage II
• Stage of Neovascularization
• Hypoxic avascular retina  upregulates VEGF/EPO
Stage II
• Aberrant retinal vessels growth in to retina and
vitreous
• More permeable  Hemorrhage and edema
Stage II
• Extensive extraretinal fribrovascular proliferation
 Retinal detachment and abnormal retinal function
• Most infants its mild and regresses spontaneously
CHRONIC STAGE-hypoxia
mediated vasoproliferation

12. Pathogenesis

13. CLASSIFICATION – ICROP
WHAT IS ?
• ZONE
• STAGE
• EXTENT
• THRESHOLD ROP
• PRE-THRESHOLD ROP
• PLUS/PRE-PLUS DISEASE
• AGGRESIVE POSTERIOR POLE ABNORMALITIES

14. CLASSIFICATION – ICROP
I-ANTERIOR-POSTERIOR LOCATION
• ZONE I:
▫ Centre: Optic disc
▫ Radius: 2 x Disc-foveal distance
▫ Boundaries: Completely surrounded by Zone II
• ZONE II:
▫ Centre: Optic disc
▫ Radius: Distance from optic disc to nasal ora-serrata and anatomic
equator temporally
▫ Boundaries: Inner-Zone I, Outer-Zone-III temporally
• ZONE III:
▫ a crescent-shaped retinal area extending beyond zone-II to the
temporal ora-serrata

16. CLASSIFICATION – ICROP
II -SEVERITY – STAGING OF ROP
• STAGE-1:
▫ a thin, sharp line of demarcation between vascularized
central retina and more peripheral avascular retina
• STAGE-2:
▫ an intraretinal elevation (ridge of fibrovascular tissue)
at the junction between vascularized and avascular retina
• STAGE-3:
▫ a ridge with extra-retinal fibrovascular extension
into the vitreous

17. CLASSIFICATION – ICROP
• STAGE-4: Partial retinal detachment (fibrovascular
tissue pulls the retina)
▫ 4A: does not involve the fovea (better vision)
▫ 4B: involves the fovea (poor vision)
• STAGE-5: Total retinal detachment (funnel shaped retina)
III-EXTENT
▫ Number of clock hours of ROP along the circumference of
the vascularized retina
▫ No longer used for treatment decisions

22. CLASSIFICATION – ICROP
IV-POSTERIOR POLE VASCULAR ABNORMALITIES
▫ PLUS DISEASE: Presence of dilated and tortuous vessels of the
posterior pole present in ≥2 quadrants
▫ PRE-PLUS DISEASE: Abnormal vascular dilation and tortuosity
that is insufficient for diagnosis of plus disease
• Aggressive posterior ROP recognized by:
▫ Marked dilation and tortuosity of posterior pole vessels(plus disease
out of proportion)
▫ Difficulty in documenting the stage of ROP at junction
between vascularized and avascular retina
▫ Occurs in zone I or posterior zone II
▫ Stage 3 with APROP can progress to stage 5 directly

25. CLASSIFICATION – ICROP
• Threshold ROP:
▫ ≥ 5 contiguous or 8 cumulative clock hours (30- degree
sectors) of stage 3
▫ with plus disease in either zone 1 or 2.
▫ This is the level of ROP at which the risk of blindness is
predicted to be at least 50% and it demands therapeutic
intervention

26. CLASSIFICATION – ICROP
• Pre-Threshold ROP:
▫ Type 1
🞄In zone 1, any ROP and plus disease or stage 3 with or
without plus disease
🞄In zone 2, stage 2 or 3 ROP with plus disease
▫ Type 2
🞄In zone 1, stage 1 or 2 ROP, without plus disease
🞄In zone 2, stage 3 ROP without plus disease

27. CLASSIFICATION – ICROP
Severity of ROP is determined by-
• Highest stage
▫ Mild to moderate – Stage I & II
▫ More serious - Stage III
▫ Emergency – Stage IV & V
• Lowest zone
▫ Mild – Zone III
▫ Most severe – Zone I & Posterior Zone II
▫ Most common – Zone II
• Plus disease - more serious
• Additional serious signs – Vitreous haze, iris vascular
engorgement, pupillary rigidity

28. Screening strategies
1.When to screen??
• The development of ROP Correlates According to infants Post mentrual age
(GA+ postnatal age) Rather than chronological age.
• As per AAP Initial examination is to be done by
, until the retina is vascularized to the
ora serrata
• Easy to remember as 1st examination at 1st month of life.

29. • AS PER NNF - initial examination to be performed
of life in infant >28weeks of gestational age
• Infants birth weight may develop early aggressive
posterior (AP)-ROP and should be
of age

30. 2.Whom to screen ??
• American guidelines given by the American Academy of Pediatrics states-
• Infants with a or less
• Selected infants with a birth weight between 1500 and 2000 g or gestational
age of more than 30 wk with an unstable clinical course, should be screened
for ROP.

31. • AS PER NNF -
• A birth weight may be used as a
cut-off for ROP screening.
• Bigger babies with a gestational age of 34 to 36 wk gestation or a birth weight
between 1750 and 2000 g should also be screened if child has a stormy
neonatal course.

32. 3.HOW TO SCREEN ??
PRECAUTIONS AND PROCEDURE FOR SCREENING
• Best performed in the presence of neonatologist
• Step-down room of NICU is ideal
• Incubator dependant babies can be screened (and even treated)
within the incubator itself through the slanting wall without
disturbing the equilibrium of the infant.
• Swaddle the baby with warm linen wraps
• Last feed approximately 1 our prior to examination
• Pupillary dilatation: Phenylephrine 2.5% and Cyclopentolate 0.5%
combination ; tropicamide 0.5-1% can be used

33. PRECAUTIONS AND PROCEDURE FOR SCREENING
• One drop in each eye, 2-3 times, 15 min apart
• Atropine should not be used for dilatation.
• Wipe off excess drops from the cheeks
• Poor dilatation may be an indicator of severe disease
• DONOT over administer eye drops, wait for
ophthalmologist to opine
• Procedure: Indirect ophthalmoscopy using a 20 D or 28 D lens or
with RETCAM imaging

34. PRECAUTIONS AND PROCEDURE FOR
SCREENING
• Peripheral scleral depression with an infant depressor and a
infant wire speculum are required
• Failure to depress may risk missing peripheral disease
• Monitor for apnea and bradycardia
• For analgesia 24% sucrose can be used
• A resuscitation kit must be accessible and functional
• Recordings of the findings should be done in the Chart or card
using standard notations.
• The date of subsequent follow-up should be clearly stated, and
the neonatologist and parent counseled about the same.

35. 4.HOW OFTEN TO SCREEN?
Zone of retinal findings Stage of retinal findings Follow-up interval
Zone 1 Immature vascularization 1-2 weeks
Stage 1 or 2 1 week or less
Regressing ROP 1-2 weeks
Zone 2 Immature vascularization 2-3 weeks
Stage 1 2 weeks
Stage 2 1-2 weeks
Stage 3 1 week or less
Regressing ROP 1-2 weeks
Zone 3 Stage 1 or 2 2-3 weeks
Regresssing ROP 2-3 weeks

36. 5.When should Retinal Screening be Terminated?
• Retinal screening is terminated based on the post- menstural
age or retinal findings:
• Full retinal vascularization; usually occurs at about the 40th
week of postmenstrual age and completes by 45 weeks.
• If Regression of ROP is noted.

37. PREVENTION STRATERGIES
DO’S AND DON’TS TO PREVENT ROP
• Avoid iatrogenic premature births
• Stringent regulated use of oxygen
-it should be used in lowest ambient conc. to treat hypoxia
-therapy should be withdrawn immediately when there is no valid
indication to administer oxygen
-Oxygen therapy should be closely monitored to
maintain PaO, between 50 and 70 mm Hg and SaO between 90 and
93%

38. PREVENTION OF ROP
• Newborn babies should not be exposed to bright light.
• Blood transfusion should be given only when absolutely indicated.
• Arterial blood gases and acid-base parameters should be
maintained within the narrow range of normality by vigilant
monitoring and prompt therapeutic interventions.
• Feeding with human milk should be promoted as it reduces the
risk of ROP.

39. PREVENTION OF ROP
• Nutrition
▫ Poor postnatal weight gain is a risk factor for ROP
▫ Start enteral feeds early or as soon as baby is
hemodynamically stable
• Avoid Hypotension
▫ Target Mean BP as per norms for GA
Prevent Late Onset Sepsis

40. PREVENTION OF ROP - STUDIES
• Lower or more tightly controlled oxygen saturation limits
early in the neonatal course reduce severity of ROP without any
adverse effects on mortality, BPD & neurological sequelae.
• Antenatal Steroids & Surfactant: Decrease RDS and hence may
decrease serious ROP
• Prophylactic Vitamin E: Till now no benefit was shown in the
trials but further research is warranted
• Reduction in light exposure: No clear benefit
• Administration of penicillamine: No clear benefit

41. PREVENTION OF ROP - STUDIES
• In some studies Insulin-like growth factor-1 (IGF-1) was
deficient in premature infants almost immediately after birth,
and they observed that children who were slow to recover to
normal serum levels of IGF-1 were more likely to
develop ROP (Hellstrom et al, 2001).
• In several careful follow-up studies, these investigators
demonstrated that determining the rate of weight gain,
essentially a noninvasive surrogate for growth hormone level,
was effective in stratifying the risk of developing serious ROP
even before the retinopathy is manifest

42. TIMING OF TREATMENT
• Current recommendations are to consider treatment for eyes with
type 1 prethreshold ROP based on the Early Treatment for ROP
(ETROP) randomized trial that showed a significant benefit for
treatment of eyes with type 1 ROP
• Close observation is currently recommended for
type 2 prethreshold ROP
• Treatment should be considered for an eye with type 2 ROP when
progression to type 1 status or threshold ROP occurs. Approximately
15% of type 2 eyes progress to type 1 ROP.

45. TREATMENT
1. LASER PHOTOCOAGULATION THERAPY
▫ Preferred initial treatment in most centers.
▫ Delivered through an indirect ophthalmoscope and is applied to the
avascular retina anterior to the ridge of extraretinal fibrovascular
proliferation for 360 degrees.
▫ An average of 1,000 spots are placed in each eye, but the number may
range from a few hundred to approximately 2,000.
▫ Both argon and diode laser photocoagulation have been
successfully used in infants with severe ROP

46. TREATMENT
1. LASER PHOTOCOAGULATION THERAPY
▫ Performed in the NICU and usually can be performed with local
anesthesia and sedation
▫ Laser therapy is as effective as cryotherapy in achieving
favorable visual outcomes
▫ Adverse effects: cataracts, glaucoma, or anterior
segment ischemia
▫Laser treatment, using the ETROP guidelines, has a
greater than 90% successful outcome.

47. Post LASER recommendation:
• The child can be fed after about 30 minutes following completion of the
procedure.
• Vital signs must be monitored. It is preferable that the child be under the
supervision of the neonatologist or an anesthesiologist for at least 2-3 hours
following the procedure.
• Post-treatment hypothermia and hypoglycemia are common and must be
prevented.
• Mild conjunctival chemosis and hyperemia following the procedure may last
for a few days and the parents must be counseled regarding this.

48. Post LASER recommendation:
• Follow-up visits recommendation: This may be typically scheduled
after week 1, 2, 4 and 12 following treatment based on the findings
recorded by the treating ophthalmologist.
• Long-term follow up for development of visual problems is also
essential.

50. TREATMENT
2. CRYOTHERAPY
▫ Indications: special cases, such as when there is poor pupillary dilation or
vitreous hemorrhage, which prevent adequate delivery of laser therapy
▫ Procedure: A cryoprobe is applied to the external surface of the sclera, and areas
peripheral to the ridge of the ROP are frozen until the entire anterior avascular
retina has been treated.
▫ Approximately 35 - 75 applications are made in each eye
▫ Usually done under general anesthesia.
▫ Cryotherapy causes more inflammation and requires
more analgesia than laser therapy
▫ Adverse effects: cataracts, glaucoma, or anterior segment ischemia

51. TREATMENT
3. ANTI-VEGF THERAPY
▫ Intravitreal injection of VEGF inhibitors(Bevacizumab) has been offered for ROP
treatment in many centers, particularly for cases of zone 1 or aggressive
posterior ROP, as salvage treatment after laser therapy or in
conjunction with vitreoretinal surgery
▫ Although use of these agents for ROP treatment is off- label, at least two
randomized trials and multiple small case series have shown the efficacy of
this treatment
▫ However, some concerns remain about dosing and safety because systemic
absorption may result in reduced VEGF and vascularization of other organ
systems.

52. TREATMENT
3. ANTI-VEGF THERAPY
▫ The ocular safety profile is reasonably good, although
endophthalmitis is a rare but potentially devastating complication
▫ Advantages:
🞄potentially less stress for the infant (because the procedure time is short and
only requires topical anesthesia);
🞄less destruction of the retina (because laser and
cryotherapy are ablative procedures); and
🞄longterm, lower rates of very severe myopia

53. TREATMENT
4. RETINAL REATTACHMENT
▫ Once the macula detaches in stage 4B or 5 ROP, retinal surgery may be
performed in an attempt to reattach the retina.
▫ Vitrectomy with or without lensectomy, and membrane peeling if
necessary, is performed to remove tractional forces causing the retinal
detachment.
▫ A scleral buckling procedure may be useful for more peripheral
detachments, with drainage of subretinal fluid for effusional
detachments.

54. TREATMENT
4. RETINAL REATTACHMENT
▫ Repeat operations for redetachment of the retina are common
▫ Even if the retina can be successfully attached, with rare exception, the
visual outcome is in the range of legal blindness.
▫ Despite the measurement of low visual acuity, children find any amount of
vision useful, and untreated stage 5 ROP eventually leads to no light
perception vision.
▫ The achievement of even minimal vision can result in a large difference in
a child's overall quality of life

55. PROGNOSIS – SHORT TERM
• Most infants with stage 1 or 2 ROP will experience
spontaneous regression.
• If prethreshold ROP develops
• ▫ 77% of type 2 eyes regress
• ▫ 32% of type 1 eyes regress

56. PROGNOSIS – SHORT TERM
• In ETROP, early treatment for type 1 ROP reduced unfavorable
visual outcomes from 33% to 25%.
• Unfortunately, only 35% of patients maintained visual acuity at
6 years of age of 20/40 or better, suggesting more work to
prevent development of ROP is needed.
• Any zone 3 disease has an excellent prognosis for
complete recovery

57. PROGNOSIS - LONG TERM
• Infants with significant ROP have an increased risk of
▫ Myopia
▫ Anisometropia
▫ Astigmatism
▫ Strabismus
▫ Amblyopia
▫ Late retinal detachment
▫ Glaucoma.
• Cicatricial disease refers to residual scarring in the retina and may be
associated with retinal detachment years later

58. PROGNOSIS - LONG TERM
• Stage 4 ROP : prognosis depends on the involvement of the
macula; the chance for good vision is greater when the
macula is not involved.
• Retinal detachment(stage 5) : the prognosis for good vision is
poor even with surgical reattachment, although some useful
vision may be preserved.

59. REFERENCES
• NNF GUIDELINES
• AAP GUIDELINES
• AVERY’S 9th EDITION
• MEHERBAN SINGH
• NELSON

60. THANK YOU