- Vasoproliferative retinopathy of prematurity (ROP) is a leading cause of childhood blindness. It affects premature infants, with risk increasing in those born under 1250g or less than 32 weeks gestation. Hyperoxia exposure and other clinical factors can also increase risk. ROP progresses through defined stages based on location and severity, with late-stage disease potentially leading to retinal detachment. Treatment involves laser photocoagulation or anti-VEGF injections to ablate peripheral retinal tissue and halt progression once pre-threshold or threshold disease is reached. Surgery may be needed for more advanced cases involving retinal detachment. With screening and timely treatment, vision loss from ROP can often be prevented.

1. DR.PRAKRITI
YAGNAM.K

2. DEFINITION :
- Vasoproliferative retinopathy of premature infants
INCIDENCE :
- 50% of preterm infants weighing <1250 gm. show
evidence of ROP and 10% of infants develop severe
ROP
- In only few severe cases RD occurs most cases
regress spontaneously

3. RISK FACTORS :
- Low birth weight and premature infants
- High oxygen exposure
- Repeated hypoxic and hyperoxic episodes
- Apnea treated by BMV
- Prolonged parenteral nutrition
- Repeated blood trasnfusions
- Episodes of hypoxemia , hypercarbia and hypocarbia

4. NORMAL RETINAL VASCULATURE DEVELOPMENT :
Vasculogenesis –
Precursor mesenchymal cells capillary network
- Begins at 16 weeks of GA
- Mature vessels reach nasal ora by 36 weeks of GA
temporal ora by 39 – 41 weeks of GA
- Full retinal vascular development occurs in utero where
relatively hypoxic environment is present (PaO2: 25-35%)

5. - Retinal vasculature is also exposed to placental and
maternal cytokines and growth factors
- And also VEGF signaling pathway , Insulin like
growth factor – 1,Wnt signaling pathway
Pathogenesis :
- Multifactorial
- Developmental , genetic and
environmental factors play role

6. premature birth and exutero hyperoxic environment
hyperoxia induced endothelial cell damage
delay in physiological retinal vascular development
vasoattenuation
Immature vessels peripheral retina continues to develop
relative hypoxia

7. secretion of proangiogenic factors
retinal neovascularization
Genetic factors :
- Missense mutation in NDP ( Norries Disease gene )
- NDP gene norrin ligand activating signal
transduction pathway
early retinal development
and
vasculogenesis

9. Classification :
- International Classification of ROP
- Clinical assessment of ROP is mainly based on
1. Extent - clock hours
2. Location - zones
3. Severity - stages

10. Zone 1 :
- Circle
- Centre – at optic disc , radius – twice the distance of disc
to fovea
Zone 2 :
- Doughnut shaped region
- Anterior border of zone 1 to one disc diameter of ora
nasally and anatomical equator temporally

11. Zone 3 :
- Residual temporal retina

12. Stage 1 :
- Thin flat white structure at junction of vascularized
retina posteriorly and avascular retina anteriorly –
demarcation line

13. Stage 2 :
- Line develops into pink or white elevation of thickened
tissue – ridge
- Small tufts of vessels are present posterior to ridge
Stage 3 :
Vessel growth into and above the ridge
extraretinal fibrovascular proliferation
into vitreous preretinal or vitreous h’age

15. Stage 3

16. Stage 4 :
contraction of fibrovascular proliferation
Traction on retina
partial retinal detachment
without foveal with foveal
involvement involvement
4a 4b

18. Stage 5 :
Funnel shaped RD
Total RD
anterior posterior
Open closed open closed
- Also called retrolental fibroplasia

19. Stage 5

21. acute / neovascular phase
progressive vascular disease
Increasing dilatation and tortuisity of peripheral retinal
vessels,engorgement of iris vessels,pupillary rigidity
A-V shunting at the ridge
Presence of marked venous dilatation and arterial
tortuosity in posterior pole PLUS DISEASE

23. Studies related to ROP :
1.CRYO – ROP study – Cryotherapy for ROP study
2. ET – ROP study – Early Treatment for ROP study
3.BEAT – ROP study – Bevacizumab Eliminates Angiogenic
Threat for ROP study

24. According to CRYO – ROP study
- Plus disease is significant dilatation and tortuosity of
vessels in all four quadrants
According to STOP – ROP and ET – ROP study
- Dilatation and tortuosity in at least two quadrants

25. Pre – Plus disease :
- Increased dilatation and / or tortuosity of retinal
arteries and / or veins in at least two quadrants of
insufficient severity for diagnosis of plus disease
progressively increasing neovascular activity at ridge
Arborization and tortuosity of blood vessels
requires laser treatment

27. Aggressive Posterior ROP ( AP-ROP )
- Also called rush disease
- In extremely premature babies (23-26 GA)
- Extremely posterior / zone 1 disease
- Neovascular fronts present – flat neovascularization
- Absence of ridge tissue
- Dilated tortuous vessels in a syncytial pattern
- Progresses rapidly to stage 4 and stage 5
- Very poor prognosis

29. Threshold ROP :
According to CRYO – ROP study
- Severity of ROP for which there is equal chance of
spontaneous regression or progression to unfavorable
outcomes
1. Stage 3 or more in zone 1 or 2 occupying atleast five
contiguous clock hours or eight non contiguous clock
hours
2. Presence of plus disease

30. Pre threshold ROP :
According to ET ROP study – before threshold disease
Type 1
- High risk
- Zone 1 – Any stage with plus disease
- Zone 1 – Stage 3 with or without plus disease
- Zone 2 – Stage 2/3 with plus disease
- Treated within 2 – 3 days of diagnosis
- Laser ablation of peripheral vascular retina

31. Type 2 :
- Low risk
- Zone 1 – Stage 1 /2 without plus disease
- Zone 2 – Stage 3 ROP without plus disease
- Observed weekly or twice weekly

32. Diagnosis :
- Examination of anterior segment – iris , lens and
tunica vasculosa lentis
- Fundus – IO with 28 D or 30 D lenses
- First PP observed without depression for plus disease
- Then scleral depression done
- Temporal retina observed first then nasal retina

33. Screening :
- All babies less than 32 weeks of GA or 1500gm.birth
weight
- Babies with unstable clinical course
- At least two examinations done
- First 4– 6 weeks of postnatal age or between 31 and
33 weeks of post menstrual age whoever is later
- Weekly examinations done when
vessels end in zone 1 / posterior zone 2
there is plus / pre plus disease
stage 3 in any zone

35. - Every other cases at two weeks interval
Devices used :
- Historical gold standard – bedside examination with
binocular IO
- Now – remote digital fundus imaging

37. DD :
- Familial exudative vitreoretinopathy
- Incontinenti pigmenti
- Stage 5 – leukocoria – Retinoblastoma
Persistent Hyperplastic Primary Vitreous
ERD ( Coats disease )
Endogenous endophthalmitis
Toxocariasis
Toxoplasmosis
Coloboma of OD , choroid
cataract
Genetic-Trisomy 13 , Norries disease , Warburg syndrome

38. Pathology :
- Ridge – anterior collection of spindle shaped cells in
NFL ( vanguard mesenchymal tissue )-precursor of
astrocytes and small posterior vascularised rearguard
- Demarcation line – hyperplasia of spindle cells
- Stage 2 – further hyperplasia plus proliferation of
endothelial cells of rearguard mesenchymal cells
- Stage 3 – proliferation of endothelial cells and small
thin walled vessels – abnormal angiogenesis

39. Treatment :
- Goal – Abolishment of angiogenic response derived
from avascular retina
- Modes
1. Cryotherapy
2. Laser photocoagulation
3. Anti VEGFs
4. Surgical Mx for cicatricial ROP

40. 1. Cryotherapy :
Indications :
Poor fundus visibility
Laser inavaibility
Physician Infamilarity
Complications :
lid edema
Laceration of conjunctiva
preretinal / vitreous h’age
bradycardia
cyanosis
respiratory depression

41. 2. Laser photocoagulation :
- 810nm. Diode laser / argon laser to prevent uptake of
laser energy by tunica vasculosa lentis or hemorrhage
of ridge vessels
End point : near confluent ablation with burns spaced
one half burn width apart from ora serrata up to ridge
360 degrees
Advantages : ease of treatment
portability
fewer systemic complications

42. Complications :
- Anterior segment ischemia
- Cataract
- High myopia
- Burns of cornea
- Damage to iris or tunica vasculosa lentis
Limitations :
- Irreversible and extensive destruction of peripheral
retina
- Laborious nature of treatment

43. - Concomitant nature in visual fields
- High level of training
Reexamination :
1 week for skip areas

45. Laser application :
- In three stages
- Typical laser treatment which is effective for most
ROP at threshold with zone 2 stage 3 disease
- Primary application of laser posterior to ridge used
when there is a high ridge along with anterior retinal
ablation
Treats ischemic retina and helps in resolution of ROP
and prevents macular drag due to fibrotic sequalae of
ROP

46. - Posterior ridge rescue treatment
To treat macular drag after primary anterior peripheral
photocoagulation with resolution of ROP but tractional
changes at ridge leading to the drag
3. Anti VEGFs :
- BEAT – ROP study showed higher recurrences in zone
1 disease with conventional laser therapy compared
with bevacizumab
- Has a role in acute zone 1 ROP

47. - 0.625mg./0.025mL delivery dose which is 1,00,000
times anti VEGF Ab as VEGF present in infants with
ROP
- Dose 0.031mg. to 0.06mg. is also shown to be effective
- RAINBOW study – Ranibizumab 0.2 / 0.1mg.
Indications :
- Treatment naïve eyes with vascular congestion of
anterior segment precluding adequate visualization
for laser treatment
- Primary monotherapy for eyes with posterior or
aggressive disease
- Infants unable to tolerate GA for laser treatment

48. Difference between Laser and Anti VEGFs
Laser Anti VEGFs
- BV become less tortuous - BV less tortuous with
But fibrovascular ridge will resolution of FVP later
be persistent causing RD progression to stage 3 & RD
- Permanent destruction - Continued vessel growth
of vessels and area treated
- VF restriction - No field changes
- Myopia more - Myopia less

49. Surgery :
- For retinal detachment
- May also progress at 41 weeks of PMA after laser
ablation
- Tractional RD – originating at ridge is a
circumferential purse string pattern draws the retina
anteriorly and centrally
- Stage 4a goal – undistorted or minimally distorted PP
Total retinal reattachment
Preservation of lens and central
fixation of vision

50. - Lens preserving vitrectomy interrupts progression
from stage 4a to 4b or 5 by addressing transvitreal
traction resulting from fibrous proliferation
Stage 4b goal – minimize retinal distortion
prevent total detachment
Functional goal – ambulatory vision
Surgery – scleral buckling + vitrectomy

51. Disadv : Dramatic anisometropia
Myopia
Second intervention for transection / removal of
buckle so that eye can grow
- Lens aspiration done in children with flat or shallow
anterior chamber due to cicatricial ROP
To prevent secondary glaucoma due to anterior pulling of
iris lens diaphragm

52. Late complications of ROP :
- Amblyopia
- Myopia
- Strabismus
- Early nuclear sclerotic cataract
- Glaucoma – acute angle closure in cicatricial ROP
- Retinal Detachment

53. Common retinal finding of regressed ROP :
- Perivascular straightening
- Pigmentary changes
- Peripheral cicatricial changes
- Vascularisation over a regressed ridge tissue
- Lattice degeneration
- Abnormal vitreoretinal interface at posterior border of
vitreous base – High retinal complications after
cataract surgery and failure rates after RD / retinal
breaks

54. Prevention :
- Judicial O2 therapy – Oxygen is a drug and it should
be administered in a quantity that is absolutely
necessary
- If a preterm neonate < 32 weeks GA needs
resuscitation FiO2 should be titrated to prevent
hyperoxia and achieve gradual increase in oxygen
saturation
- Judicious blood transfusion – Adult RBCs are rich in
2,3 DPG and adult Hb binds less firmly to O2 thus
releasing excess O2 to retinal tissue
- Daily 15 -25 IU of Vit E to LBW neonates

55. Follow up :
Post screening :
- All preterm infants – Throughout first year
- Children treated for ROP – Till preschool year
- With threshold ROP – adequate treatment + fully
regressed disease – at 3 months
- cycloplegic refraction – at 6
months