DR.

BHARTI AHUJA
INTRODUCTION
 Proliferativeretinopathy affecting premature infants of low
birth weight and young gestational age(Terry,1942).
 Term was coined by HEATH(1951).

CRUCIAL RISK FACTORS

 BIRTHWEIGHT
 GESTATIONAL AGE
 OXYGEN SUPPLEMENTATION
Risk factors(associated)
 Prematurity
 Hyper/hypoxia
 Hypotension
 Acidosis
 Blood transfusions
 Sepsis
 Antioxidant deficiency
 Apnoea
 PDA
 Vitamin E deficiency
 JOURNAL OF AAPOS,AUG 2009,VOL 13 ISSUE 4, pg 370-73
RONALD G.W.TEED,RICHARD A. SAUNDERS
Retinopathy of prematurity in extremely premature infants

Introduction
The incidence and severity of retinopathy of prematurity (ROP) in
extremely premature infants have not been reported since publication of
the Early Treatment of ROP study results. The survival rate of these
infants continues to increase. We sought to determine the characteristics
of ROP in a group of surviving infants <25 weeks estimated gestational
age (EGA) at birth compared to a group 25 to 27 weeks EGA at birth.

Methods

Retrospective review of infants born prior to 27 weeks EGA between

January 2003 and July 2007 at a level-3 nursery at a regional academic
medical center.
Results
 A total of 231 medical records were reviewed and found to
have analyzable data. Of 79 infants <25 weeks EGA, 69
(87%) developed ROP, compared to 95 of 152 (62%)
infants 25 to 27 weeks EGA. Type 1 ROP developed in
23% of infants in the <25 weeks EGA group, compared to
9% of infants in the 25 to 27 weeks EGA group. There was
no difference in mean postmenstrual age when type 1 ROP
was diagnosed. Lower birth weight predicted increased risk
of type 1 ROP in the 25 to 27 weeks EGA group, but not in
the <25 weeks EGA group.

Conclusions
 Extremely premature infants are more likely to develop
ROP and type 1 ROP, but the incidence may be lower than
previously reported. Birth weight may not influence the
incidence of type 1 ROP in this group of infants. Type 1
ROP does not develop at an earlier postmenstrual age in
the extremely premature infant
Pathogenesis of ROP
PHASE I
 True vasculogenesis
 Occurs at 8-21 wks of
gestation.
 Not Under the control of
VEGF.
 Mesenchymal cells
differentiate into
capillaries,subsequently
develop into arterioles and
venules.
PHASE II
 Angiogenesis
(Physiologic and pathologic)
 22-40 wks of gestation.
 VEGF controls this phase.
 Proliferating endothelial
cells migrate from existing
bld vessels to form new
capillaries.
Spindle cell theory(kretzer
etal,1984) Preterm newborn
Term newborn

Relatively higher hyperoxic envt

Thin,avascular retina
Relatively less hyperoxic Spindle cells(defective )
environment
Spindle cells(normal antioxidative
property)
Gap junctions
Angiogenic factor(VEGF)

Normal migration and canalization Migration and canalization halt

Neovascularization at shunt site

Mature vessels formation Myofibroblasts REGRESSIO

from stem cells N
Contractile sheet
ROP
CURRENT
CLASSIFICATION,ICROP,198
7
PLUS DISEASE
SEVERITY
AREA OF
RETINA
INVOLVED

STAGE 1-5
EXTENT IN
LOCATION
CLOCK
ZONES I-III
HOURS
ICROP STAGING
ROP: STAGES DESCRIPTION
STAGE 1
STAGE 2 Demarcation line
STAGE 3 MILD/MODERATE/ Ridge
SEVERE
Ridge with extraretinal
STAGE4 fibrovascular
A proliferation
B Subtotal retinal
STAGE 5 detachment
A.Not involving macula
B.Involving macula
Total retinal detachment
STAGE 1
STAGE 3
 STAGE 4B
STAGE 4A
Funnel shaped
RD(STAGE 5)

Open opeop
Retrolental fibroplasia

Leukocoria resuting from fibrovascular

proliferation and advanced Retinal
detachment.
Classification based on
location/clock hours
Plus disease
Aggressive posterior(AP-
ROP)/RUSH Disease

Rapid progression through the three

stages of ROP, with plus disease
 THRESHOLD ROP
STAGE 3 + ROP IN ZONES 1 / 2 OCCUPYING ATLEAST FIVE
CONTIGUOUS OR EIGHT NON CONTIGUOUS CLOCK HOURSOF RETINA
Early treatment of retinopathy of
prematurity(ETROP)Cooperative group
classification(Arch,ophthalmology2003-04)
TYPE 1 PRETHRESHOLD TYPE 2 PRETHRESHOLD

 Zone I ROP(any stage)+  Zone I stage 1/2 -

 Zone I stage 3  Zone II stage 3-
 Zone II stage 2/3 +

 High risk  low risk

 Immediate treatment  Observation,treat when
progresses to threshold
ROP.
Screening for ROP
 To detect the babies with treatable disease
in time for treatment to be effective.

Which and when to

screen???????

 At 31 wks post conceptional

age(gestational age+post natal age) or 4-5
wks after birth whichever is later.
Which children to
screen??
 Screen all premature infants less than 1500 g
birth weight.
 Screen all babies born at less than or equal to
32wks of gestational age(postmenstrual age).
 Selected preterm infants,birth wt between
1500-2000g or gestational age of more than
32 wks with an unstable clinical
course(including those requiring
cardiorespiratory support, who are believed to
be at a higher risk (SICKNESS CRITERIA)
STANDARD SCREENING
PROTOCOL
 Inform neonatology unit nurse regarding time of
examination.
 Instruct nurse regarding pupillary dilatation of eyes.
 Avoid feeding of infants until 60 mins after examination.
 Attending neonatologist should be there, especially in
cases which are unstable.
 Maintain asepsis.
 Low light of indirect ophthalmoscope(+20D/
+28Dlens),look for plus disease.
 First screen nasal retina.
 Draw retinal chart.
BRITISH JOURNAL OF OPHTHALMOLOGY, MARCH
2009,VOL.93,
ISSUE 3;pg355-59

C Dhaliwal,E Wright, C Graham,N Mcintosh,B W Fleck

Wide-field digital retinal imaging versus binocular
indirect ophthalmoscopy for retinopathy of
prematurity screening: a two-observer prospective,
randomised
Aim: comparison
To compare the diagnostic accuracy of wide-field digital retinal
imaging (WFDRI) with the current “gold standard” of binocular
indirect ophthalmoscopy (BIO) for retinopathy of prematurity (ROP)
screening examinations.
Methods:
A consecutive series of premature infants undergoing ROP screening
at Edinburgh Royal Infirmary were eligible for recruitment into this
prospective, randomised, comparative study. Infants were screened
using both WFDRI (Retcam II with neonatal lens) and BIO by two
paediatric ophthalmologists who were randomised to the
examination technique. Both examiners documented their clinical
findings and management plans in a masked fashion. WFDRI eye
findings were compared with those of BIO.
 Results: A total of 81 infants were recruited, and information
from 245 eye examinations was analysed. The sensitivity of
WFDRI in detecting any stage of ROP, stage 3 ROP and “plus”
disease was 60%, 57% and 80%, respectively, and specificity
91%, 98% and 98%, respectively. The proportional agreement
between WFDRI and BIO was 0.96 for detecting stage 3 disease
and 0.97 for detecting “plus” disease. There was very good
agreement on management decisions (kappa 0.85).

Conclusion:
When used in a routine ROP screening setting, a
randomised comparison of WFDRI and BIO, WFDRI showed
relatively poor sensitivity in detecting mild forms of ROP in
the retinal periphery. This resulted in difficulty in making
decisions to discharge infants from the screening
programme. Sensitivity was better for more severe forms
of ROP, but at present WFDRI should be regarded as an
adjunct to, rather than a replacement for, BIO in routine
ROP screening.
 AMERICAN JOURNAL OF OPHTHALMOLOGY JULY 2009, VOL 148,ISSUE
1,pg 136
SPEED OF TELEMEDICINE VS OPHTHALMOSCOPY FOR DIAGNOSIS OF RO

AIM: To compare the speed of retinopathy of prematurity (ROP)

diagnosis using standard indirect ophthalmoscopy with that of
telemedicine.
METHODS:
Three study examiners (2 pediatric retinal specialists [R.V.P.C., T.C.L.]
and 1 pediatric ophthalmologist [M.F.C.]) conducted ROP diagnosis via
standard indirect ophthalmoscopy and telemedicine. Each examiner
performed: 1) standard ophthalmoscopy on 72 to 150 consecutive
infants at his respective institution and 2) telemedical diagnosis on 125
consecutive deidentified retinal image sets from infants from an at-risk
population. Time for ophthalmoscopic diagnosis was measured in 2
ways: 1) time spent by the examiner at the infant's bedside and 2)
mean total time commitment per infant. Time for telemedicine
diagnosis was recorded by computer time stamps in the web-based
system. For each examiner, nonparametric statistical analysis (Mann–
Whitney U test) was used to compare the distribution of times for
examination by ophthalmoscopy vs telemedicine
 RESULTS:
Mean (± standard deviation [SD]) times for ophthalmoscopic
diagnosis ranged from 4.17 (± 1.34) minutes to 6.63 (± 2.28)
minutes per infant. Mean (± SD) times for telemedicine diagnosis
ranged from 1.02 (± 0.27) minutes to 1.75 (± 0.80) minutes per
infant. Telemedicine was significantly faster than ophthalmoscopy
(P < .0001). The total time commitment by ophthalmologists
performing bedside ophthalmoscopy for ROP diagnosis, including
travel and communication with families and hospital staff, was
10.08 (± 2.53) minutes to 14.42 (± 2.64) minutes per infant

CONCLUSION:
The ophthalmologist time requirement for telemedical ROP diagnosis
is significantly less than that for ophthalmoscopic diagnosis.
Additional time requirements associated with bedside ROP diagnosis
increased this disparity. Telemedicine has potential to alleviate the
time commitment for ophthalmologists who manage ROP
Treatment
options(available)
 Ablative therapy(cryotherapy and laser)
 Scleral buckling surgery
 Lens sparing vitrectomy
 Lensectomy +vitrectomy
 Open sky vitrectomy
 Anti VEGF injections(controversial)
Guidelines for treatment of
ROP(Ablative therapy)
 Stage 1 or 2 ,progressing to stage 3
 All stage 4a cases
 Extraretinal fibrovascular proliferation
present in more than 3contiguous or 5
cumulative clock hours in zone 1/2
 Presence of plus disease
Comparison of ablative
therapy
Cryotherapy Laser

 Transscleral  Direct ablation

 Very painful  Less painful
 Require ventilation during procedure  No need for ventilation
 Substantial lid swelling and  Less local complications
conjunctival edema.  Posterior retina can be reached more
 Posterior retina difficult to reach. readily.
 In small pupil ,easy to do.  Difficult.
 Myopia and retinal detachments are  less common.
problems.  Possible risk
 No risk of damage to iris,and  Expensive
cataractformation during the  More precise
procedure.

 Longer time
Low cost
 Diffuse treatment
 Shorter time.
Fundus showing multiple white cryo burns (black
arrows) in avascular retina anterior to ridge (white
arrow).
 JOURNAL OF EYE(ONLINE),APRIL, 2009

Long-term visual outcomes of laser-treated threshold retinopathy of

prematurity: a study of refractive status at 7 years

Yang CS, Wang AG, Sung CS, Hsu WM, Lee FL, Lee SM.

Purpose
To assess the long-term visual outcomes and refractive status in patients
with diode laser-treated threshold retinopathy of prematurity (ROP), and to
investigate the causes of impaired visual function

Method
A total of 60 eyes of 30 consecutive patients with diode laser-treated
threshold ROP were recalled for assessment at the age of 7 years or more.
Results
There were 38 eyes (65.5%) achieving 6/12 or better vision, however, an
unfavourable visual outcome (6/60 or worse) occurred in four eyes (6.9%). One
eye (1.7%) had unfavourable structural outcome. Of these 60 laser-treated eyes,
46 eyes (77.0%) were myopic, the overall mean spherical equivalent was -3.87
D. Anisometropia (>/=1.5 D) was also noted in 14 patients (46.7%). Strabismus
was present in nine patients (30.0%). Perinatal neurological events of
intraventricular haemorrhage (IVH) were identified in eight children (26.7%),
periventricular leucomalacia (PVL) in eight children (26.7%), and cerebral palsy
(CP) in four children (13.3%). There was a statistically significant association of
the presence of strabismus with PVL (P=0.002). The presence of anisometropia
was a significant risk factor associated with poor visual outcome of 6/15 or worse
in laser-treated ROP (P=0.002)

Conclusion
The majority of patients with diode laser-treated threshold ROP had favourable
anatomical and visual outcomes. However, anisometropia, advanced refractive
error, strabismus, and perinatal neurological events remain important causes of
impaired visual function. Long-term follow-up is very important for early
detection and timely treatment of these ocular morbidities.
Indian J Ophthalmol. 2009 Jul-Aug;57(4):267-71

Functional and anatomical outcomes after primary lens-sparing

pars plana vitrectomy for Stage 4 retinopathy of prematurity.

Bhende P, Gopal L, Sharma T, Verma A, Biswas RK

To assess the functional and visual outcomes after primary lens-sparing pars
plana vitrectomy for Stage 4 ROP.

MATERIALS AND METHODS: In a retrospective, interventional,

consecutive case series, the records of 39 eyes of 31 patients presenting
with Stage 4 retinal detachment secondary to ROP who underwent primary
two or three-port lens-sparing vitrectomy from January 2000 to October
2006 were evaluated. The outcomes studied at the final follow-up visit
were the retinal status, lens and medial clarity and visual acuity . Favorable
anatomical outcome was defined as the retinal reattachment of the
posterior pole at two months after the surgery; and favorable functional
outcome was defined as a central, steady and maintained fixation, with the
child following light.
 RESULTS: At mean follow-up of 15 months, 74% of the eyes had a
favorable anatomical outcome with single procedure. The visual status was
favorable in 63% . The lens remained clear in all the eyes at the last follow-
up, and the media clarity was maintained in 87%. Intraoperative
complications included vitreous hemorrhage, pre-retinal hemorrhage and
retinal break formation.

CONCLUSION
Lens-sparing vitrectomy helps to achieve a favorable anatomical and
functional outcome in selected cases of Stage 4 ROP.
ONLINE JOURNAL OF
OPHTHALMOLOGY,2009,OCTOBER

Effect of Early Vitreous Surgery for Aggressive Posterior Retinopathy of

Prematurity Detected by Fundus Fluorescein Angiography

Nishina S, Yokoi T, Yokoi T, Kobayashi Y, Hiraoka M, Azuma N.

OBJECTIVE: To assess the effect of early vitrectomy for aggressive

posterior retinopathy of prematurity (APROP) using fundus fluorescein
angiography.

METHODS: All eyes underwent vitrectomy with lensectomy that removed

the vitreous gel around the fibrovascular proliferative tissue, but not the
proliferative tissue when fibrovascular proliferation and retinal detachment
occurred despite retinal photocoagulation. Fundus fluorescein angiography
was performed before and after the early vitreous surgery.
RESULTS: Nine eyes had severe dye leakage from the fibrovascular tissue
and 2 eyes had moderate leakage seen by preoperative fluorescein
angiography. Severe dilation and tortuosity of the retinal vessels were
detected in 10 eyes and shunt vessels in 7 eyes. Six to 12 days after
successful surgery, the retina reattached and dilation and tortuosity of the
retinal vessels decreased substantially. Dye leakage diminished markedly in
all eyes, resolved completely in 7 eyes, and was still apparent slightly in 4.
At the final examination, fibrovascular proliferation and retinal detachment
did not progress in any eyes; however, 2 eyes had a dragged or folded
retina. Follow-up ranged from 6 to 19 months (mean,9.2)

CONCLUSIONS:
Early vitrectomy that removes vitreous gel from around the proliferative
tissue promptly reduces vascular activity and may limit progression of
retinal detachment in APROP.
 BRITISH JOURNAL OF OPHTHALMOLOGY,92, 2008,PG 1450-55

Efficacy of intravitreal injection of bevacizumab for severe retinopathy of

prematurity: a pilot study
S Kusaka, C Shima, K Wada, H Arahori, H Shimojyo, T Sato, T Fujikado

To evaluate the short-term efficacy of intravitreal injections of bevacizumab for

severe retinopathy of prematurity (ROP).

Methods: A retrospective chart review was conducted of 23 consecutive eyes

(stage 3, three eyes; 4A, 18 eyes; 4B, two eyes) of 14 patients with vascularly
active ROP considered at high risk for progression or development of tractional
retinal detachment despite conventional laser ablation therapy. Patients
received an intravitreal injection of bevacizumab (0.5 mg), either as the initial
treatment (15 eyes) or at the end of vitrectomy (eight eyes)
Results: After injection of bevacizumab as the initial treatment, reduced
neovascular activity was seen on fluorescein angiography in 14 of 15
eyes. In three eyes, a tractional retinal detachment developed or
progressed after bevacizumab injection. No other ocular or systemic
adverse effects were identified. Vitrectomy was performed in 20 eyes
and the retina was reattached after one surgery in 18 eyes. Multiple
surgeries were necessary in two eyes, resulting in retinal reattachment.

Conclusion: There results suggest that intravitreal injection of

bevacizumab seems to be associated with reduced neovascularisation
without apparent ocular or systemic adverse effects, and is thus beneficial
for treating severe ROP that is refractory to conventional laser therapy.
Differential diagnosis
 Retinoblastoma
 Familialexudative vitreoretinopathy
 Coats’ disease
 Toxocariasis/toxoplasmosis
 Persistent primary hyperplastic vitreous
 Congenital X-linked retinoschisis
 Incontinentia pigmenti
COMPARISON RETINOBLASTOMA
ROP

 Usually negative.
 History of prematurity, low birth
 Positive(25-30%cases,bilateral)
wt ,oxygen usage.
 Usual time of presentation is 6-
 Family history negative.
18 mths.
 Leukocoria may be detected  Unilateral usually.
after 6-8 wks.
 Heterogenous mass with
 Clinical findings bilateral.
haemorrhages,many vessels on
 Leukocoria-fibrotic look,a ridge surface.
with cicatricial vessels in  Calcification(large% of cases)
periphery.
 Origin of mass from underlying
 No significant lesion on X-ray.
retina.
 B-scan-complex pattern of  Calcification within the mass.
detachment.
 CTscan-no specific pattern
Sequelae of ROP
 Spontaneous regression
 MYOPIA
 STRABISMUS
 AMBLYOPIA
 CATARACT
 GLAUCOMA
 RETINAL BREAKS/DETACHMENT
AMERICAN JOURNAL OF OPHTHALMOLOGY APR 2009,VOL 147,
,ISSUE 4 pg-661-66

Kondo H, Arita N, Osato M, Hayashi H, Oshima K, Uchio E.

Late recurrence of retinal detachment following
successful vitreous surgery for stages 4B and 5
retinopathy of prematurity.
PURPOSE: To determine the incidence and possible causes of a late
recurrence of a retinal detachment (RD) in eyes with stages 4B and 5
retinopathy of prematurity (ROP), in which the retina was once
reattached by lensectomy and vitrectomy
METHODS: The medical records of 124 eyes of 99 infants and
children <2 years of age at the time of initial vitrectomy, in which
the retina had been reattached for at least 1 year, were
reviewed. The incidence of a recurrence of the RD >1 year after
the initial surgery for eyes at stage 4B ROP (42 eyes) was
compared with that in eyes at stage 5 ROP (82 eyes). The onset
and symptoms were evaluated.
 RESULTS: A recurrent RD occurred in 2 eyes (5%) at stage 4B
ROP and 18 eyes (22%) at stage 5 ROP (P = .01). The recurrence
developed at 2 to 10 years of age (median, 4 years). Prior to the
recurrence, clear signs of traction on the peripheral retina were
detected in 10 eyes (50%): localized residual RDs in 8 eyes, and
peripheral retinal breaks in 2 eyes. Dense vitreous hemorrhage
was present in 5 eyes (25%) at the time of the recurrence.

CONCLUSION:
The retina of eyes at stage 5 ROP is more vulnerable to a recurrence
of the RD than in eyes at stage 4B after being attached by vitrectomy.
The time of recurrence varies widely, and the presence of traction on
the peripheral retina may be a sign of a recurrence.
PREVENTION OF ROP
 Judicious oxygen therapy
 Judicious use of blood transfusions
 Strict clinical and electronic monitoring
 Vitamin E supplementation
 Prenatal steroids
PROGNOSIS
 Predicted by the stage of retinopathy of
prematurity.
 Patients who did not progress
beyond stage I or stage II have a good
prognosis.
 Patients with posterior zone I disease or
stage III, IV, or V have a guarded
prognosis for their vision.
 !!
y ou
a n k
Th