retinopathy of prematurity: laser, anti-vegf,surgery & others dr. mangat r. dogra professor of...

Retinopathy of Prematurity: Laser, Retinopathy of Prematurity: Laser, Anti-VEGF,Surgery & Others Anti-VEGF,Surgery & Others

Dr. Mangat R. Dogra

Professor of Ophthalmology

Advanced Eye Centre

PGIMER, Chandigarh

No financial disclosure

IntroductionIntroduction Retinopathy of prematurity (ROP) is the leading cause of

childhood blindness worldwide.

Becoming a major public health concern in developing countries like India. (New and emerging cause of blindness)

Blindness due to ROP is potentially preventable.

A large number of babies in our country are presenting late with bilateral, irreversible blindness due to absence or delayed screening.

Predicting ROP blindness according to Infant mortality rates.Gilbert C. Early Hum Dev 2008;84 (2):77-82.

ROP in IndiaROP in India Incidence of ROP: 38% – 47. 3 % in low birth weight

infants.– Charan R, Dogra MR, Gupta A, Narang A. Indian J Ophthalmol 1995; 43:123-26. – Gopal L et al. Indian J Ophthalmol 1995; 43:50-61.

Live births: 26 million /year Incidence of Low birth weight (< 2000g)- 8.7% 2 million newborns are at risk for developing ROP.

National Neonatalogy Forum of India. National Neonatal Perinatal Database. Report New Delhi 2005

Indian scenario of ROP Indian scenario of ROP

1995 : Charan R ,Dogra MR et al IJO 43:123-126;1995 first prospective study (<1700g)

incidence of 47.27% 1995 : Gopal etal ; (<2000g) 38% 1996 : Rekha etal ; (<1500g) 47.3% 1996 : Maheshwari etal; (<1500g) 20% 2001 : Varughese etal; (<1500g) 51.89% 2009 : Chaudhari etal; (<1500g) 22.30% 2012 : Hungi B etal; (<2000g) 41.5%

Implications for screeningImplications for screening

The American screening guidelines

Babies ≤ 1500 g birth weight or ≤ 30 weeks gestational age

Selected infants with a birth weight 1500 -2000 g or gestational age > 30 weeks be screened at the discretion of the attending neonatologist.

Pediatrics 2013;131(2)

Indian Screening guidelines

Infants weighing < 1750 grams or < 34 weeks of gestation.

Heavier (1750-2000g) or older babies (34-36 weeks) may be screened depending upon the attending risk factors like mechanical ventilation, prolonged oxygen therapy, hemodynamic instability or adverse respiratory or cardiac disease profile.

National neonatology forum. Clinical practice guidelines 2010.

Why screen for ROP Why screen for ROP

Premature child is not born with ROPScreening aims to identify treatable stage Narrow window for screening and treatmentDelay cause blindness or visual impairmentMedico-legal implicationsEconomic and social burden of childhood

blindness is immense

Aggressive Posterior ROP Aggressive Posterior ROP

The keys to diagnosis: Identification of plus

disease Location in zone 1 or

posterior zone 2 Subtle neovascular

findings at the junction without any stages of ROP

ICROP revisited:ICROP revisited:Arch Ophthalmol.2005;1239:991-99Arch Ophthalmol.2005;1239:991-99

These cases progress rapidly and directly to retinal detachment .

Jalali S, Kesarwani S, Hussain A.Outcomes of a protocol-based management for zone 1 retinopathy of prematurity: the Indian Twin Cities ROP Screening Program report number 2.Am J Ophthalmol. 2011 Apr;151(4):719-724

Sanghi G, Dogra MR et al.Aggressive posterior retinopathy of prematurity in Asian Indian babies:Spectrum of Disease and Outcome After Laser Treatment. Retina 2009:29;1335-39

Shah PK, Narendran V, Kalpana N Aggressive posterior retinopathy of prematurity in large preterm babies in South India. Arch Dis Child Fetal Neonatal Ed. 2012 Sep;97(5):F371-5.

AuthorAuthor yearyear CountryCountry Mean Birth Mean Birth weight (g)weight (g)

Mean gestational Mean gestational age (wk)age (wk)

Jalali et alJalali et al 20112011 IndiaIndia 12281228 29.6329.63

Drenser et alDrenser et al 20102010 USAUSA 627627 24.324.3

Sanghi et alSanghi et al 20092009 IndiaIndia 12591259 29.7529.75

Azuma et alAzuma et al 20062006 JapanJapan 773773 2525

Shah et alShah et al 20122012 IndiaIndia 15721572 31.731.7

The mean birth weight and The mean birth weight and gestational age in APROPgestational age in APROP

Current treatments of ROPCurrent treatments of ROP

Peripheral retinal ablation with laser delivered through laser indirect ophthalmoscope (LIO) is a gold standard in ROP treatment

Anti-VEGF is emerging therapy for selective cases of ROP

Vitreoretinal surgery is required in stage 4 and 5 ROP

Rationale for laser treatmentRationale for laser treatment

VEGF is stimulus for abnormal vessels which comes from avascular retina

Ablate the avascular retina between ora and ridge to reduce VEGF

Laser Treatment of ROPLaser Treatment of ROP

Laser treatment earlier than threshold ROP has shown better results & outcome

after ETROP Study

Arch Ophthalmol.121:1684-1696; 2003

ETROP RecommendationsETROP Recommendations

Stage 1 Follow

Stage 2 Follow

Stage 3 Treat

Stage 1 Treat

Stage 2 Treat

Stage 3 Treat

Stage 1 Follow

Stage 2 Follow

Stage 3 Follow

Stage 1 Follow

Stage 2 Treat

Stage 3 Treat

Zone 1

Zone 2

No Plus

Plus

No Plus

Plus

Arch Ophthalmol. 121:1684-96;2003

Plus diseasePlus disease

If pupil does not dilate suspect tunica vasculosa lentils and plus disease.

Plus diseasePlus disease

Plus disease means at least 2 quadrants of dilation and tortuosity of the posterior retinal blood vessels

Preplus & Plus diseasePreplus & Plus disease

Laser treatmentLaser treatmentDelivered in

confluent pattern (less than half burn width apart)

Around 90% attain favourable outcome

Laser treatment for ROP: evolution in treatment technique over 15years Hurley et al. Retina 26: S16-7; 2006

Laser treatmentLaser treatment

Possible inside the incubator through the slopping transparent wall in

extremely unstable premature infants

Dogra etal Ophthalmic Surg Lasers Imaging 39:350-352;2008

Frequency doubled Nd: YAG Frequency doubled Nd: YAG (532 nm green) versus diode laser (810 (532 nm green) versus diode laser (810

nm) in treatment of ROPnm) in treatment of ROP

Favorable outcome in 97% with 532 nm laser versus 96.9% in diode laser group.

Treatment possible in eyes with TVL, vitreous or preretinal hemorrhage and without inducing any cataract, anterior segment ischemia or hyphema .

Sanghi G, Dogra MR, Vinekar A,Gupta A. Frequency doubled Nd: YAG (532 nm green) vs diode laser(810 nm ) in treatment of retinopathy of prematurity

Br J Ophthalmol 94;1265-1265 : 2010

Laser treatment Laser treatment of APROPof APROP

Delivered through LIO in confluent pattern (less than half burn width apart) with in 24-48 hours of diagnosis

Around 55% to 84% attain favourable outcome in reported series

Sanghi G, Dogra M R et al. Aggressive posterior retinopathy of prematurity in Asian Indian babies:Spectrum of Disease and Outcome After Laser Treatment.Retina 2009:29;1335-39

APROP in posterior zone 1 with mat like proliferation

Unfavourable outcome after laser

Risk factors for RD after laser Risk factors for RD after laser treatment of APROPtreatment of APROP

Gestational age less than 29 weeksPosterior zone 1 APROPPre-retinal hemorrhagesNeed for repeat laser treatmentNew onset fibrovascular proliferation after

laser treatmentSanghi G, Dogra M R et al.Aggressive posterior retinopathy of prematurity: risk factors for RD despite confluent laser photocoagulation. Am J Ophthalmol. 2013: Jan;155(1):159-164

Indications for ROP surgeryIndications for ROP surgery

Progression despite laser treatment Delayed or no screening Stage 4A, 4b and stage 5 ROP Bilateral cases

Current surgical Current surgical approaches in ROP approaches in ROP

Scleral buckle is rarely performed Lens sparing vitrectomyLensectomy & vitrectomy

Management of stage 4A and Management of stage 4A and 4B ROP4B ROP

? Observation if < 4 clock hrs of elevation

Lens sparing vitrectomy has shown reattachment in 60 % to 85% eyes

Bende P, Gopal L et al. Indian J Ophthalmol 57:267-271;2009

Lakhanpal et al. Arch Ophthalmol 124: 675-679;2006

Capone A Jr, Trese MT. Ophthalmology 108:2068-2070;2001

Lens sparing vitrectomy Lens sparing vitrectomy (LSV)(LSV)

Most important recent innovationIdeal for stage 4A and 4B ROPBoth 2 or 3 port LSV is possible23G and 25G LSV are preferred at present

ROP stage 5 : Total retinal detachment

Management of stage 5 ROPManagement of stage 5 ROP Lensectomy and vitrectomy in these cases Reattachment in some eyes (< 1/3) Functional results extremly poor and dismal

ETROP Study results: Arch Ophthalmol 124;24-30:2006 Arch Ophthalmol 129;1175-1179:2011 Shah et al. Eye 23;176-180:2009 Gopal et al. IJO 48:101-106; 2000

Bevacizumab monotherapyBevacizumab monotherapy

Avastin monotherapy showed a significant benefit for zone 1 but not for zone 2 ROP as compared to conventional laser therapy.

Trial was too small to assess safety issue.

Mintz-Hittner et al. N Engl J Med 2011; 364:603-15

Avastin in ROPAvastin in ROP

Caution is warranted for routine use at this time due to safety issues.

0.625mg in 0.025ml of intravitreal avastin is usually given.

Mostly used as rescue therapy in zone 1 ROP along with laser

Increasing ROP blindness in Increasing ROP blindness in IndiaIndia

High rate of preterm birthNeonatal care not optimalROP screening and treatment programs not

in placeInadequate treatment and follow upIncreasing numbers of NICUs and SNCUs

SNCUsSNCUs

Sick Newborn Care UnitsDistrict levelProvide newborn care to decrease mortalityPotential sources for ROP in the coming

years

ROP Stage 5

86.4% of infants presenting with stage 5 ROP were never screened

74.2% were picked up by the parents when they noticed that child is not seeing.

Pediatricians referred none 25.8% referred by an ophthalmologist.

– Sanghi G, Dogra MR, Katoch D, Gupta A. Demographic profile of infants with stage 5 retinopathy of prematurity in North India: implications for screening. Ophthalmic Epidemiol 2011;18(2):72-4.

Prevailing clinical practices among pediatricians

Only 14.5% were following the recommendations for ROP referral.

– Patwardhan SD, Azad R, Gogia V, Chandra P, Gupta S. Prevailing clinical practices regarding screening for retinopathy of prematurity among pediatricians in India: a pilot survey. Indian J Ophthalmol 2011;59(6):427-30.

Role of neonatologist and / or Role of neonatologist and / or pediatricianpediatrician

Prevention of ROPROP screeningDuring ROP treatment / surgeryFollow up of cases

Prevention of ROPPrevention of ROPPrevention of prematurityGood antenatal and obstetrics care

1.Use of antenatal steroids

2.Trained personal in delivery room to avoid asphyxia

Judicious use of oxygen therapy and ventilation

Reduce morbidity of premature infants

ROP screeningROP screening

Single nodal person to be identifiedCommunicate with parents and ophthalmologistIdentify babies and decide time for screeningCombine ROP screening visit with follow up for

neonatal problemsRecord keeping is most important

During laser therapyDuring laser therapy

Monitoring during therapyCounselingResuscitation

What should be doneWhat should be done

Wall chart regarding whom to screen, when to screen and how to dilate should be pasted in NICU and Nursery

What should be doneWhat should be done

Any one weighing the new born infant should paste a bold sticker on card / file for ROP screening in babies < 1750gms at birth in 3 to 4 weeks.

Responsibility is of Obstetrician / Pediatrician / nurses to get ROP screening done from Ophthalmologist at appropriate time

A novel, low-cost method of enrolling infants at risk for Retinopathy of Prematurity in centers with no screening program: the REDROP study.Vinekar A, Avadhani K, Dogra M, Sharma P, Gilbert C, Braganza S, Shetty B.Ophthalmic Epidemiol. 2012 Oct;19(5):317-21

Goals of an ROP workshopGoals of an ROP workshop

Define criteria for identification of babies at risk with birth weight and gestational age

Develop programs for prevention, detection and treatment of ROP

Develop teams at NICUs with no programPrepare action plan for prevention of ROPStimulate government participation

Conclusions Conclusions Lack of awareness about ROP in IndiaNeonatal care and screening program are

variable not optimalMore mature and higher birth weight babies are

developing ROPDelayed or no screening responsible for

increasing rates of childhood blindness due to ROP in India

ConclusionsConclusionsTreat ROP as per ETROP Study

recommendations & with APROP promptly with confluent laser

Use anti-VEGF as rescue therapy.Lens sparing vitrectomy is the most important

recent exciting innovation for stage 4A and 4B.Lensectomy and vitrectomy in complex cases

usually results in poor outcome.ROP prevention, screening and management is a

team effort

THANK YOUTHANK YOU

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