Ophthalmology, retinopathy of prematurity

1. PRESENTER- DR. SHILPA HEDAOO
DNB OPHTHALMOLOGY
CIVIL HOSPITAL FARIDABAD
Retionopathy of prematurity

2. DEFINITION
• Retinopathy of prematurity (ROP) of developing retinal
vasculature is multifactorial vasoproliferative retinal
disorder is a disorder of premature,LBW infants featuring
abnormal proliferation of developing blood vessels at the
junction of vascular and the avascular retina
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

3. NORMALRETINALVASCULATUREDEVELOPMENT
• The first blood supply to the inner retina appears as “spindle cells
from the adventitia of the hyaloids artery at about 16wks of GA.
Spindle cells canalize and metamorphose into mature vessels.
and reach the nasal ora serrata
• 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
• Before the retinal vessels develop the avascular retina receives
oxygen by diffusion from the choroid vessels.It achieves the adult
pattern by the 5th month after birth.

4. Nasal
Temporal

5. PATHOphysiology of rop
1. The classical theory- proposed by arthon and patz
2. Spindle cell theory-proposed by Kretzer et al
3. The current theory/recent theory-experimental and clinical
evidence suggest that disease proceeds in 2
phasesfluctuations in retinal oxynation.
PHASE 1 of ROP begins from birth (before approx. 31wks of
GA)
PHASE 2 of ROP begins over the ensuing weeks (by 32-
34wks of GA)

6. Stage I
• Hypoxia
• Hypotension
Stage I
• Vasoconstriction and decreased blood flow to
developing retina
• Arrest of vascular development
Stage I
• Hypoxia causes down regulation of
harmones /growth factor(VEGF) cessation
of VEGF driven vessel growth and vaso- obliteration
of parts of retinal vasculature by vascular
endothelial cells apoptosis and excessive capillary
regression with retinal ischemia
IN PHASE 1 ROP

7. Stage II
• Stage of Neovascularization
• Hypoxic avascular retina  upregulates
VEGF/IGF-1
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
IN PHASE 2 ROP which is hypoxic driven

8. RECENT ADVANCES IN PATHOphysiology-
1. ROLE OF OXYGEN FREE RADICALS IN ROP-The balance
between the production and catabolism of oxygen metabolites is
essential in maintaining normal physiological conditions-
Increased level of superoxide in the retina under hyperoxic
conditions.
2. Insulin like Growth Factor – lack of insulin-like growth factor I
(IGF-I) in knockout mice prevents normal retinal vascular
growth
3. Granulocyte Colony–Stimulating Factor
4. Jun Kinases (Jnk) Inhibitors

9. CLASSIFICATION– ICROP
 The International Classification of Retinopathy of Prematurity
(ICROP1) was published in 1984 under the leadership of John
Flynn later expanded in 1987.
 ICROP was revised in 2005 (ICROP2)by adding:
1) The concept of a more virulent form of retinopathy –
APROP (Aggressive posterior Retinopathy of
Prematurity).
2) Description of an intermediate level of vascular dilatation and
tortuosity of posterior pole vessels that are insufficient for the
diagnosis of plus disease(i.e.Pre-plus disease)

10. MOST RECENTLY IN 2021( ICROP3)
retains current definition such as ZONE,STAGE and CIRCUMFERENTIAL
EXTENT OF DISEASE
Major updates in ICROP3 include refined classification metric
1. Posterior zone II
2. Notch
3. Subcategarization of stage 5(5A, 5B, 5C)
4. Recognition that a continuous spectrum of vascular abnormalities exists
from normal to plus disease
5. Replace AP-ROP to Aggressive ROP(may occurs beyond the posterior
retina
6. Detail description of ROP Regression and Reactivation
7. Description of long term sequelae

11. The original ICROP requires 4 defining concepts for ROP
1. ANTERIOR-POSTERIOR LOCATION or ZONE of involvement
2. EXTENT of disease(measured in clock hours0
3. SEVERITY or STAGING OF ROP
4. Presence or absence of PLUS DISEASE(dilatation and tortuosity
of vessels in ZONE 1)

12. CLASSIFICATION – ICROP
I-ANTERIOR-POSTERIOR LOCATION/ZONE
• 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

14. ICROP3 UPDATE
POSTERIOR ZONE II-ICROP3 defined a region that
begins at the margin between Zone I and Zone II for 2
disc diameters peripheral to zone border.Indicates
more worrisome disease than ROP
NOTCH-an incursion by the ROP lesion of 1-2clock
hours along the horizontal meridian into the more
posterior zone(e.g “zone I secondary to Notch”)

16. III-EXTENT
 Number of clock hours of ROP along the circumference of the
vascularized retina(from 1-12)
 No longer used for treatment decisions

17. II SEVERITY – STAGING OF ROP
STAGE-0 :Immature retinal vasculature without pathological changes
STAGE-1: DEMARCATION LINE: a flat, thin, white demarcation line
between the vascularized and the avascular retina. The vessels end abruptly
at the demarcation line with no vessels extending beyond it

18. STAGE 2- a demarcation line with height,width, and
volume(RIDGE); small, isolated tufts of neovascular tissue lying
on the surface of the retina commonly called popcorn may be
seen posterior to ridge.

19. STAGE 3 –
• External fibrovascular proliferation
or neovascularization that extends
from the ridge into the vitreous.
The severity of the lesion can be
subdivided into-
1. Mild- presence of only limited
amount of vascular tissue.
2. Moderate: Significance amount
tissue infiltrating into the vitreous.
3. Severe: massive infiltration of
tissue surrounding the ridge is
seen.

20. STAGE 4- a partial retinal detachment
• 4a – Extra foveal partial retinal detachment (RD)
• 4b – Partial RD involving the fovea

21. STAGE -5 – Total retinal detachment –currently classified by
configuration of the funnel(ICROP3)
• Open-Open(a)
• Open-closed(b)
• Closed-open(C)
• Closed-closed(d)

22. STAGE -5 – Total retinal detachment
Subcategarised into 3 configuration
A. Optic nerve head is visible by
ophthalmoscopy(open funnel
detachment).
B. Optic nerve head is not visible by
ophthalmoscopy due to retrolental
fibrosis or (closed funnel
detachment).
C. 5B with anterior segment
abnormalities (e.g.Anterior les
displacement, marked AC
shallowing, central CO,iridocapsular
adhesion, capsule-endothelial
adhesion).

23. Icrop3update
Stage of Acute Disease(Stage1-3)- is defined by the
appearance of the structure at the vascular and avascular
junction as Stage1(demarcation line), Stage2 (Ridge),
and Stage3 (Extraretinal neovascular proliferation or flat
neovascularisation)
•Retinal detachment (Stages 4 and 5)
•Subcategarization of stage 5(5A, 5B, 5C)

25. • PLUS DISEASE:used to indicate abnormal vascular
dilatation(venous) and tortuosity(arteriolar) of posterior pole
vessels in at least 2 quadrants (usually 6 or more clock hours)
of the eye;iris vascular dilatation and vitreous haze may be
present.
• PRE-PLUS DISEASE:recent classification uses thus term to
describe eyes Abnormal vascular dilation and tortuosity that is
insufficient for diagnosis of plus disease
IV-POSTERIOR POLE VASCULAR
ABNORMALITIES

26. AGGRESSIVE ROP
Earlier known as ‘RUSH Disease’ and ‘(AP-ROP)
Aggressive posterior ROP’
A rapidly progressive, severe form of ROP often but not
always Posterior location
• Rapidly evolving pre-plus and plus disease
neovascularization that may be subtle or even
intraretinal in nature, sometimes iris rubeosis:
the peripheral retinopathymay be ill defined
• Progress to stage IV & V in 2-3 weeks without passing
through characteristic stages II and III

27. PLUS DISEASE AP-ROP

28. • Threshold ROP:
▫ ≥ 5 contiguous clock-hour Or 8 cumulative clock hours (30-
degree sectors) of extraretinal neovascularization location at
Zone 1 Or 2 with plus disease
• Pre-Threshold ROP:
▫ Type 1
• 🞄
zone I, any ROP and plus disease or
• Zone I, stage 3 without plus disease or
• 🞄
zone II, 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
As an extension of these concepts further classify ROP can help
to optimize management and treatment.

29. RISKFACTORS
• Low birth weight/Prematurity/Small for gestational age
• Respiratory distress syndrome/ surfactant therapy/ oxygen
therapy > 24 hours
• Multiple blood transfusions
• Pneumothorax
• Documented necrotising enterocolitis
• Severe intraventicular haemorrhage
• Patent ductus arteriosus requiring pharmacological or
surgical closure
• Hypotension requiring vasopressor therapy
• Delivery room resuscitation requiring chest
compression/medications
• Sepsis

30. • The procedure is performed at NICU by pediatric
opthalmologist , under the supervision of neonatologist so
that complication can be handled.
• The pupil are dilated with a mixture of phenyl phrine 2.5%
and tropicamide 0.4 % or cyclopentolate 0.5% instilled 3
times at 10min intervals before the scheduled examination.
• Topical anesthetic and lid speculum should be used to
reduce discomfort.
• Indirect opthalmoscopy is performed with 20D / 30D lens
using fresh sterile instruments.
• Scleral depression is done to stabalize the eye , rotate it ,
indent it.
• RETCAM can be used to provide real time video display of
images
SCREENINGPROCEDURE

31. SCREENING OF ROP(KIDROP)
The need for a ROP screening program arises from the fact that
• ROP is a blinding disease
• Identification of all babies is essential who are at risk or likely to get severe
ROP
• Timely and early detection prevents undesirable sequel and
progression to advanced stages
Current guidelines for screening- by American Academy of
Ophthalmology
1. Infants with birth weight of less than 1500g or GA of 32Wks or less
2. Infants with birth weight between 1500g to 2000g /GA > 32Wks with
unstable clinical course, including those requiring cardio-respiratory
support.

32. • Wide angle digital paediatric
retinal imaging system
• Mobile, self contained system for
use in nursery, ICU, O.T
• Easily used by technicians or
nurses
• Provide retinal images at 130
degree
• Avoids stress & expertise of I/O
examination & indentation, but as
specific and sensitive as I/O
• Useful for diagnosis,
telemedicine &
documentation

33. SCREENINGINTERVAL
A) FOLLOW-UP IN 1-WEEK OR LESS
•Immature vascularisation: zone I—no ROP
•Immature retina extends into posterior zone II, near the boundary of
zone I
•Stage 1 or 2 ROP in zone I
•Stage 3 ROP in zone II
• the presence or suspected presence of aggressive posterior ROP
B) FOLLOW-UP IN 1- TO 2-WEEK
•Immature vascularisation; posterior zone II
•Stage 2 ROP in zone II,
•Unequivocally regressing ROP in zone I

34. C) FOLLOW-UP IN 2-WEEK
•Stage 1 ROP in zone II,
•Immature vascularisation: zone II—no ROP,
•Unequivocally regressing ROP in zone II
D) FOLLOW-UP IN 2- TO 3-WEEK
• Stage 1 or 2 ROP in zone III,
• Regressing ROP in zone III

35. • COMPLETE VASCULARIZATION
• VASCULARIZATION in ZONE III (till 1 DD of temporal
ora) – if no previous ROP in zone I & II
• REGRESSED ROP ( b/w 40 -44 weeks PCA)– no active
disease left
• 45 weeks PCA with less than pre threshold disease
TERMINATIONOF SCREENING

36. • RETINALABLATION
– CRYO
– LASER
• ANTI-VEGF
• SCLERAL BUCKLING
• VITRECTOMY
– LENS SPARING
– With LENSECTOMY
TREATMENT

38. (Continued..)

39. • Mostly outdated
• Firstly used by hindle and leyton
• Rationale- elimination of production of vasoproliferative
factor
produced by avascular retina
• Indications-
CRYOTHERAPY

40. LASER PHOTOCOAGULATION THERAPY
According to ETROP study, current indications for laser
treatment are high risk ROP-
1) Zone I, stages 1-3 ROP with plus disease
2) Zone I, stage 3 ROP without plus disease
3) Zone II, stage 2 or 3 ROP with plus disease
• In the past decade, laser photoablation has almost
supplanted cryotherapy as the standard treatment for ROP.
• Procedure of choice,less invasive, less traumatic and causes
less discomfort to the infant.
• Compared to cryotherapy, laser photoablation better structural
and visual outcomes, fewer post-operative complications and
less myopia.
▫

41. • Laser treatment is delivered through an indirect
opthalmoscope .
• It can be performed in NICU and under local
anesthesia
• Easy to treat posterior located lesion.
• Argon green and Diode red LASER has been used
• An average of 1000 to 2000 spots of 100 mm size 1½ burn
width apart can be placed in each eye.
• Entire avascular retina till ora, avoid the ridge.
• End point – grade II gray burn

42. • ⦿ Monotherapy
• Single injections
• Multiple injections for recurrence
• Less desirable if periphery not perfused
• ⦿Adjunctive therapy
• Injections to allow regression beyond Zone 1
• Laser for recurrent ROP
• Anti-VEGF as a Bridge to laser peripherally
• Treatment after laser / cryotherapy failure
• ⦿ Perioperative therapy before surgery
• Reduce bleeding
• Promote regression of neovascularization
• Vitrectomy and scleral buckles
ANTIVEGF

43. • GOAL- increase likelihood and vision of each patient
• Pathophysiologically – proliferation of epiretinalglial cells in stage
4/5 ROP,the membranes exert traction and lead to retinal
detachment
• Once the macula detaches in stage 4b or 5 ROP retinal
reattachment is done.
SURGERY

45. SCLERAL BUCKLE
• done for progressive stage 4a and 4b
• It is done under GA
• Peritomy 2.5 mm encircling band passed beneath 4 recti
• One anchoring mattress 4-0 ethibond suture applied in all
quadrants, final knot in temporal quadrant( easy removal)
• Removal after 3-6 months

46. VITRECTOMY
• INDICATIONS- detachment in stage 4b/5 too severe to be
relieved by scleral buckling alone, recent rapid progression
to detachment, extensive total RD
• Treat pupillary block glaucoma and corneal edema
before sx
• GOAL- complete release of preretinal tissue with
release of traction
• Approach- closed and open sky

47. TECHNIQUE
• Peritomy, infusion canula 1-1.5 mm from limbus
• Standrad pars ciliaris entry to avoid subretinal entry of
instruments
• Lensectomy done only when required
• Multiple radial incisions made in retrolental plane
towards equitorial area, creating stellate appearance
• Delamination and peeling of membranes- cut as closely
as possible to retina
• SRF drainge- usually not necessary (
non rhegmatogenous)
COMPLICATIONS-
• Iatrogenic retinal breaks, haemmorhage, corneal clouding

48. Icrop3update
Regression- Definition of ROP regression and its sequelae,
whether spontaneous or after laser or Anti-VEGF treatment.
Regression can be complete or incomplete. Location and extend
of peripheral avascular retina (PAR) should be documented
Reactivation- Definition and description of ROP reactivation after
Treatment include new ROP lesions and vascular changes.When it
Occurs, the modifier reactivated(e.g., “reactivation Stage2) is
Recommended.

49. LONGTERM sequelae
Emphasized beyond previous version of ICROP,including such
as
• Late retinal detachment
• Retinoschisis
• PAR (persistant avascular retina)-prone to retinal
thinning,holes,lattice like changes
• Macular Anomalies-small FAZ, blurring/absence of foveal
depression
• Retinal vascular changes-persistent tortuosity,
straightening of vascular arcade with macular dragging and
falciform retinal fold. Vitreous haemorrhage may occur.
• Glaucoma-secondary angle closure glaucoma

50. THANKYOU