retinopathy of prematurity

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Information about retinopathy of prematurity

Published on March 2, 2014

Author: RohitRao2



retinopathy of prematurity

Presented by Dr Rohit Rao

1. Hs Niranjan & Et Al,Retinopathy Of Prematurity –Promising Newer Modalities Of Treatment, Indian Pediatrics 139 Volume 49,February 16, 2012. 2. Clinical Practice Guidelines Of Retinopathy Of Prematurity, December 2005 Moh/P/Pak103.05 (Gu) 3. AIOS CME series on Retinopathy Of Prematurity no. 12. 4. Ranjan Kumar Pejaver & et al Retinopathy of Prematurity, NNF Clinical Practice Guidelines Page | 253 5. Deepak Chawla & et al, Retinopathy of prematurity, AIIMS- NICU protocols 2010 6. Retinopathy of Prematurity by Tapas Ranjan Padhi

 1942- Terry first identified ROP as ‘retro lental fibroplasia” in 6 month premature infant.  1951 - Heath suggested term “Retinopathy of Prematurity”  Campbell: relationship of intensive oxygen therapy & subsequent development of ROP.  Kinsey: ROP was inversely proportional to birth weight.

 It is a developmental vascular proliferative disorder that occurs in the incompletely vascularized retina of primarily premature infants.  ROP is one of the most common causes of blindness in children

      Choroid vascularises at 6 weeks Retinal vascularisation starts at optic nerve head at 16 weeks gestation Proceeds outward to the periphery Vascularisation is almost complete by term Vasculogenesis: primitive plexus formed from precursor cells, not VEGF dependant Angiogenesis: new vessels from pre existing vasculature, VEGF dependant

 Classical theory Arthon & Patz  O2  Vasoconstriction-vasoocclusion-endothelial cell proliferation-neovascularization   Spindle   cell theory Kretzer Spindle cell exposure to hyperoxic environmentspindle cell insult- spindle cell stops to migration & canalization

Premature delivery interrupts normal vascular growth  Phase 1 : delayed retinal vascularisation (birth31/32 weeks) Developing retina exposed to hyperoxic environment (ambient and supplemental)  Reduces angiogenic factors delaying retinal vascularisation   Phase 2 : neovascularisation  Neuroretina continues to develop causing hypoxia with overproduction of angiogenic factors especially VEGF  Causes uncontrolled retinal blood vessel growth

Hypotension, hypoxia, or hyperoxia, with free radical formation, injures newly developing blood vessels and disrupts normal angiogenesis  neovascularization retinal edema, hemorrhage and abnormal fibrovascular tissue development.

 ICROP  Zone, Stage, Extent, Plus  ICROP    (1984 & 1987 ) revisited APROP Pre plus Practical clinical tool for extent of Zone I

 Four     features are evaluated: Zone (1-3) Extent Stage (1-5) Presence or absence of plus disease

 Zone I: retinal area within a circle centered on the disk and with a radius of twice the estimated disk-foveal distance  Zone II: retinal area extending from the edge of zone I to a circle with a radius from the disk to the nasal ora serrata  Zone III: a crescent-shaped retinal area extending beyond zone II to the temporal ora serrata

 The extent of disease is described by dividing the retinal surface into 30º sectors, similar to the hours of a clock.  As many as 12 clock hours can be affected, and the stage of retinopathy can vary among sectors.

 Four     features are evaluated: Zone (1-3) Stage (1-5) Extent Presence or absence of plus disease

 Stage 5: Total tractional funnel shaped RD of one of the 4 different configurations     Anterior Open, Posterior Open Anterior Open, Posterior Narrow Anterior Narrow Posterior open Anterior Narrow posterior narrow

 Four     features are evaluated: Zone (1-3) Stage (1-5) Extent Presence or absence of plus disease

 Plus disease: Presence of dilated and tortuous vessels of the posterior pole present in two or more quadrants

 Preplus disease: Abnormal vascular dilation and tortuosity that is insufficient for diagnosis of plus disease present in two or more quadrants

Aggressive posterior ROP recognized by: 1. marked dilation and tortuosity of posterior pole vessels 2. difficulty in documenting the stage of ROP at junction between vascularized and avascular retina 3. occurs in zone I or zone II

ROP is defined as five contiguous clock hours or eight total clock hours of stage 3 and plus disease in zone 1 or 2.

Defined as one of the following:  ROP at any stage less than threshold in zone 1  Stage 2 and plus disease in zone 2  Stage 3 without plus disease in zone 2  Stage 3 with plus disease in zone 2 but with fewer clock hours of stage 3 than required to meet threshold

 Grade 0 None visible  Grade 1 Minimal to mild (view of underlying retina not significantly reduced)  Grade 2 Moderate to marked (view of underlying retina significantly obscured)

The most important risk factor for developing ROP is prematurity.  More than 50 separate risk factors have been identified.  On multivariate analysis, low birth weight, low gestational age, assisted ventilation for longer than one week, surfactant therapy, high blood transfusion volume, and cumulative illness severity were independently associated with higher rates of ROP 

 Myopia occurs in about 80% of infants with ROP  Strabismus and amblyopia are also common residual findings.  23% to 47% in infants with ROP  RD  seen in 22% patients. Can occur as early as 6 months up to 31 years from the time of diagnosis  Acute angle closure glaucoma can be seen in cicatricial ROP

    Screening of at risk babies Diagnosis Decision to treat or not Treatment  Tt. of ROP itself ...     Cryotherapy ( mostly outdated) Laser treatment (gold standard) Anti-VEGF (adjuvant) before laser and surgery Surgery Correction of systemic factors  Rx of ROP related complications    Post treatment follow up Rehabilitation

 Should be performed in all preterm neonates who are < 34 weeks gestation and / or < 1750 grams birth weight.  34 to 36 weeks gestational age or a birth weight between 1750 and 2000 grams with risk factors.  First screen should be performed not later than 4 weeks of age or 30 days of life in infants ≥ 28 weeks of gestational age.  Infants <28 weeks or <1200 grams birth weight should be screened early at 2-3 weeks of age, for early diagnosis of AP-ROP. 

 Retinal   examinations may be terminated if Full retinal vascularization; occurs at 40th week of postmenstrual age and completes by 45th week Regression of ROP noted

 To dilate pupil: 2.5%Phenylepherine +1% Tropicamide, twice, 10 minutes apart.  Watch the pulse and respiration.  Screening & Tt. can be done in minor OR/OPD/NICU.  Under topical anesthesia without any sedation  Indirect ophthalmoscope and a 20 D or 28 D lens.  Record the findings

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


 Mature  Vessels reached with in 1DD of both nasal and temporal ora  Immature   Vessels not reached with in 1DD of nasal or temporal ora Immature I,II,III(depending on zones)  ROP

 Cryotherapy ( mostly outdated)  Laser treatment (gold standard)  Anti-VEGF (adjuvant) before laser and surgery  Surgery

 Based on results of ETROP two new terminologies have been suggested:  Type 1 ROP: Zone I, any stage ROP with plus disease  Zone I, stage 3 ROP with or without plus disease  Zone II, stage 2 or 3 ROP with plus disease   Type 2 ROP: Zone I, stage 1 or 2 ROP without plus disease  Zone II, stage 3 ROP without plus disease   Peripheral retinal ablation should be carried out for all cases with type 1 ROP and continued serial examinations are advised for type 2 ROP

 Cryotherapy significantly improves the outcome of severe ROP  Superceded by laser photocoagulation  Cryotherapy applications are applied contiguously. Probe placed trans-sclerally anterior to ridge in avascular zone. End point of cryotherapy is the appearance of mild whitening. 360 degrees circumference, under direct visualization avoid the ridge.     Complications of cryotherapy  Eyelid edema, laceration of the conjunctiva, and pre-retinal and vitreous haemorrhage as well as systemic complications like bradycardia, cyanosis and respiratory depression

Procedure of choice, being less invasive, less traumatic and causes less discomfort to the infant.  Easy to treat posterior located lesion.  Argon green and Diode red  1500 to 1800 spots, 100 mm size 1½ burn width apart.  Entire avascular retina till ora, avoid the ridge.  Complications of laser therapy   Burns in cornea and iris. Other complications include cataract, and retinal and vitreous haemorrhage.

 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

Interventions to prevent or limit the progression of ROP have been unsuccessful, further evaluation may be needed. Antioxidant therapies, such as vitamin E D-penicillamine limited exposure to light, have been tested. Supplemental oxygen therapy Insulin-like growth factor-1(IGF-1)

RCT (172 infants)  Peripheral Cryotherapy vs. Observation  “Threshold Disease”   Stage 3 (neovascularization)  5 contiguous, 8 noncontiguous clock hours Zone I or II  Plus Disease   Cryotherapy superior to Observation: Reduced unfavorable outcomes  Related improved visual acuity results 

 RCT (n=317 bilateral; n=84 asymmetric unilateral infants)  Early peripheral laser vs conventional treatment  “High Risk Prethreshold” ROP disease – Type 1 or Type 2  Type 1 ROP   Zone II: Stage 2 or 3, plus   Zone I: Any Stage, plus / Stage 3, no plus Finding: Early Peripheral laser superior to conventional treatment Type 2 ROP   Zone II: Stage 3, no plus   Zone I: Stage 1 or 2, no plus Finding: Observation advised until Type 1 or Regression Peripheral laser better than conventional treatment for Type 1:  Reduced unfavorable anatomic outcome from 15.6% to 9.1%  Reduced unfavorable visual acuity grating from 19.5% to 14.5%

      “Bevacizumab Eliminates the Angiogenic Threat in ROP” RCT (150 infants, 300 eyes) Stage 3, plus Zone 1 and posterior Zone 2 Comparison : Intravitreal Bevacizumab v/s Peripheral Laser (ETROP) Summary    Bevacizumab reduced recurrence of ROP Bevacizumab benefit over laser in Zone 1 Bevacizumab allowed continued peripheral vascularization into avascular retina

 152 eyes with Zone 1, posterior Zone 2 ROP Stage 3, plus disease  Group 1 (68 eyes)    Group 2 (84 eyes)     Pegaptanib (0.3 mg) with laser Follow up 19.3 months Laser / cryotherapy Follow up 21.5 months Primary Outcome: absence of recurrent Stage 3+ ROP Results   Group 1 89.7% regression; 85.4% no recurrence Group 2 60.8% regression; 50% no recurrence



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