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1. RETINOPATHY OF PREMATURITY
- Dr. LOKANADHA REDDY
Fellow in Neonatology
OVUM Hospitals
Bangalore

2. DEFINITION
• Retinopathy of prematurity (ROP) is a
multifactorial vasoproliferative retinal
disorder that increases in incidence with
decreasing gestational age
• It’s a disease of developing retinal
vasculature

3. DEFINITION
• Retinopathy  Affects retinal vasculature
• Prematurity  typically in <30 weeks or
<1500gm
Prevalence:
• 65% of newborns with B.wt <1,250g and
• 80% of newborns with a B.wt <1,000 g will
develop some degree of ROP

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. PATHOGENESIS
Stage I
• Hyperoxia, Hypoxia
• Hypotension
Stage I
• Vasoconstriction and decreased blood flow to
developing retina
• Arrest of vascular development
Stage I
• Hyperoxia causes down regulation of VEGF
that is essential for normal development of retinal
vessels

8. PATHOGENESIS
Stage II
• Stage of Neovascularization
• Hypoxic avascular retina  upregulates VEGF
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

9. CLASSIFICATION – ICROP 2005
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
▫ Boundaries: Inner-Zone I, Outer-Zone-III temporally
• ZONE III:
▫ a crescent-shaped retinal area extending beyond
zone-II to the temporal ora-serrata

11. CLASSIFICATION – ICROP 2005
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

12. CLASSIFICATION – ICROP 2005
• 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

14. CLASSIFICATION – ICROP 2005
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

15. CLASSIFICATION – ICROP 2005
• 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 at
which the CRYO-ROP study showed that the risk
of blindness could be reduced to approximately
25% with appropriate treatment.

16. CLASSIFICATION – ICROP 2005
• 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

17. CLASSIFICATION – ICROP 2005
Status 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

18. NATURAL HISTORY
▫ Begins at 31-33 weeks GA
▫ Progresses over next 2-5 weeks
▫ Spontaneous regression – Stage I&II and Early
stage III
▫ Blindness or severe visual impairment – Retinal
detachment or severe distortion of posterior retina

19. RISK FACTORS
Low gestational age – single most
important risk factor
Low birth weight
Poor postnatal weight gain/delay in
return to B.wt in 14 days
Mechanical ventilation
Lability in oxygen
requirement(hypoxia-hyperoxia)
Prolonged oxygen exposure
Hypercarbia
Males>Females IVH
Anemia
Blood transfusion(HbA-> more
oxygen delivery)
Exposure to light
Unstable clinical course
Late onset sepsis/Candida sepsis
Hypotension
Acidosis
Vitamin E defeciency

20. PREVENTION OF ROP
DO’S AND DON’TS TO PREVENT ROP
• Avoid iatrogenic premature births
• Stringent regulated use of oxygen
▫ Use a pulse-oximeter
🞄Soon after the birth
🞄During resuscitation
🞄Transport to NICU
🞄Transport to another facility
🞄 During NICU stay

21. PREVENTION OF ROP
▫ Attach pulse-oximeter preferably to RUL after birth
▫ Remember SpO2 takes 3-5 minutes to increase after
birth. Avoid oxygen administration if baby has good
respiratory efforts
▫ FiO2 recommendation for resuscitation of preterm
infants: 30-90% only
▫ If using BMV for PPV remove reservoir and
ventilate. This will ensure FiO2 < 40%
▫ If using Neopuff for PPV use oxygen-air blender and
start with 30% FiO2. Adjust based on SPO2 readings

22. PREVENTION OF ROP
▫ Target SPO2 of 88-92%
always(resuscitation/NICU/transport)
▫ Avoid large changes in FiO2 during desaturation
episodes n NICU. Increase or decrease by 5% at a
time and evaluate each time
▫ Have a display of Oxygen saturation
recommendation on a wall in NICU
▫ Remember: Sicker the baby, higher is the risk of
developing ROP

23. PREVENTION OF ROP
• Aggressive Nutrition
▫ Poor postnatal weight gain is a risk factor for ROP
▫ Use TPN for all babies <31 weeks / <1250gm
▫ Start enteral feeds early or as soon as baby is
hemodynamically stable
• Avoid Hypotension
▫ Target Mean BP as per norms for GA

24. PREVENTION OF ROP
• Prevent Late Onset Sepsis
▫ Strict asepsis precautions
▫ Contact isolation for all babies
▫ Strict sterile precautions while preparing and
starting IVF. Two health care professionals should
prepare the fluids ideally. Discard any leftover IVF
bottle 24 hours after it is opened
▫ Avoid interrupting IV infusion lines once initiated

25. 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

26. 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

27. SCREENING OF ROP (KIDROP)
• WHOM TO SCREEN?
▫ All preterm infants with B.Wt <1750 gm
(mandatory) or <2000gm(preferred)
▫ GA <34 weeks
▫ Up to 36 weeks with risk factors
▫ Do not exclude any baby based on the absence of
risk factors if they are eligible by weight or
prematurity
▫ Remember even if you don’t give an ounce of
oxygen, ROP can still develop
▫ Screening to continue till 44 weeks of GA

28. SCREENING OF ROP (KIDROP)
• WHEN TO SCREEN?
▫ Before 30 days of life
▫ Best practice: Between 3rd&4th week of life irrespective
of GA
▫ Between 2nd&3rd week of life for babies <1200gm or
<28 weeks
▫ 2 weeks for <28 weekers and 3 weeks for >28 weekers
▫ Initiating timely screening is the responsibility of the
neonatologist
▫ Delay in screening is liable to medico legal scrutiny
▫ A sick child is more likely to develop ROP. Don’t delay

29. SCREENING OF ROP (KIDROP)
• PRECAUTIONS AND PROCEDURE FOR SCREENING
▫ Best performed in the presence of neonatologist
▫ Step-down room of NICU is ideal
▫ Last feed approximately 1 our prior to examination
▫ Pupillary dilatation: Phenylephrine 2.5% and
Cyclopentolate 0.5% (Auropent plus eye drops)
▫ One drop in each eye, 2-3 times, 15 min apart
▫ Wipe off excess drops from the cheeks, blocking punctum
also advisable
▫ Poor dilatation may be an indicator of severe disease
▫ DONOT over administer eye drops, wait for
ophthalmologist to opine

30. SCREENING OF ROP (KIDROP)
• PRECAUTIONS AND PROCEDURE FOR
SCREENING
▫ Swaddle the baby with warm linen wraps
▫ Procedure: Indirect ophthalmoscopy using a 20 D or 28
D lens or with RETCAM imaging
▫ 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 10%Dextrose/24% sucrose can be used
▫ A resuscitation kit must be accessible and functional

31. SCREENING OF ROP (KIDROP)
• SCHEDULE AND DOCUMENTATION
▫ Maintain a fixed day, fixed time each week
▫ Avoid ROP screening on ad-hoc basis
▫ Details of dilatation, schedule and list of babies to
screen must be printed and displayed in NICU
▫ Documentation should be according to ICROP
classification
▫ Parents should be given a card with diagnosis and
follow up date
▫ Counseling the parents about the disease and need for
follow up is the key to improve compliance

32. SCREENING OF ROP (KIDROP)
• SCHEDULE AND DOCUMENTATION
▫ Inform the neonatologist about the baby status
▫ If your hospital has no ROP specialist, arrange for
the nearest doctor to visit your facility
▫ Photo-documentation on wide-field digital
imaging is better for documentation, medico-legal
evidence and does not miss even peripheral and
minimal disease
▫ Baby can have multiple retinal findings besides
ROP. Digital imaging is best for this

33. TELEMEDICINE
• KIDROP-KARNATAKA INTERNET ASSISTED
DIAGNOSIS OF ROP
• Started by Narayana Nethralaya in 2008 in
Karnataka
• Uses RETCAM shuttle – widefield digital imaging
technology to send images to be analyzed by the
experts at the centre
• Triple T philosophy
▫ T: Tele ROP
▫ T: Training of peripheral ophthalmologists and
ophthalmic assistants
▫ T: Talking to neonatologist

34. 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.

35. 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

36. TREATMENT
1. LASER PHOTOCOAGULATION THERAPY
▫ Performed in the NICU and usually can be
performed with local anesthesia and sedation
▫ Laser therapy is at least as effective as
cryotherapy in achieving favorable visual
outcomes
▫ Adverse effects: cataracts, glaucoma, or
anterior segment ischemia

37. 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

38. 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.

39. 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

40. 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.

41. 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

42. PROGNOSIS – SHORT TERM
Risk factors for ROP requiring treatment include
▫ posterior location (zone 1 or posterior zone 2)
▫ presence of ROP on the first examination
▫ increasing severity of stage
▫ circumferential involvement
▫ plus disease & rapid progression
• 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

43. 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

44. 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

45. 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.

46. PROGNOSIS - LONG TERM
• All premature infants who meet screening
criteria regardless of the diagnosis of ROP are at
risk for long-term vision problems, from
either ocular or neurologic abnormalities
• A follow-up evaluation is recommended by an
ophthalmologist with expertise in neonatal
sequelae at approximately 1 year of age or
sooner if ocular or visual abnormalities have
been noted

47. REFERENCES
• AVERY’S 9TH EDITION
• CLOHERTY 8TH EDITION
• KIDROP-KARNATAKA INTERNET ASSISTED
DIAGNOSIS OF ROP