Retinopathy Of Prematurity Sigal Peter-Wohl MD Mark Kadrofske MD PhD

Retinopathy Of PrematurityRetinopathy Of Prematurity

Sigal Peter-Wohl MDSigal Peter-Wohl MD

Mark Kadrofske MD PhDMark Kadrofske MD PhD

ROPROP

Definition - Vasoproliferative disorder of the retina Definition - Vasoproliferative disorder of the retina which occurs principally in the preterm infant.which occurs principally in the preterm infant.

Specifically, occurs in the incompletely vascularized Specifically, occurs in the incompletely vascularized retina.retina.

A vascular problem.A vascular problem.

ROPROP

•Originally described as “retrolental fibroplasia” in theOriginally described as “retrolental fibroplasia” in the early 1940s, owing to (overly?) aggressive oxygen use.early 1940s, owing to (overly?) aggressive oxygen use.

•Nearly disappeared between 1954-1970, when oxygen Nearly disappeared between 1954-1970, when oxygen use severely restricted.use severely restricted.

•But now, has returned, secondary to improved neonatal But now, has returned, secondary to improved neonatal practice of VLBW infants. practice of VLBW infants.

•Est. 400 infants blinded each yr; 4300 with serious Est. 400 infants blinded each yr; 4300 with serious retinal scars.retinal scars.

ROP Incidence: MHMC NICU 1997-2001ROP Incidence: MHMC NICU 1997-2001

BW(g)BW(g) %ROP (all) GA (wks) %ROP (all) %ROP (all) GA (wks) %ROP (all)

0-5000-500 11 11 0-230-23 2222

501-750 45501-750 45 24-2524-25 4545

751-1000 42751-1000 42 26-2726-27 4545

1001-1250 121001-1250 12 28-2928-29 2020

1251-1500 41251-1500 4 30-3130-31 6 6

1501-1750 0.81501-1750 0.8 32-3332-33 1 1

1751-2000 0.41751-2000 0.4 34-3534-35 0.20.2

>2000>2000 0 0 >35>35 0 0

ROP - Pathogenesis

•ROP can occur when the retinal vessels have not yetROP can occur when the retinal vessels have not yet

completed their centrifugal growth from the optic disccompleted their centrifugal growth from the optic disc

to the ora serratia. to the ora serratia.

•Primitive endothelial cells (“spindle cells”) form cordsPrimitive endothelial cells (“spindle cells”) form cords

that canulize into capillaries and further differentiatethat canulize into capillaries and further differentiate

into arterioles and venules.into arterioles and venules.

ROP - PathogenesisROP - Pathogenesis

16 weeks of gestation - 16 weeks of gestation - primitive spindle cells primitive spindle cells gradually grow out over the gradually grow out over the surface of the retina. surface of the retina.

29 weeks -reached ora 29 weeks -reached ora serrata. At this time these serrata. At this time these spindle cells start to form spindle cells start to form blood vessels. blood vessels.

The vessels reach the anterior The vessels reach the anterior edge of the retina and stop edge of the retina and stop their progression at about the their progression at about the time of birth.time of birth.


During vasculogenesis if the retina is exposed to toxic During vasculogenesis if the retina is exposed to toxic substance or other insult normal (e.g., hypoxia, increased substance or other insult normal (e.g., hypoxia, increased oxygen, shock, preterm delivery) vasculogenesis is oxygen, shock, preterm delivery) vasculogenesis is interrupted. A sharp demarcation line appears between inner interrupted. A sharp demarcation line appears between inner vascular and outer avascular zone.vascular and outer avascular zone.

After the “injury,” vessel growth can resume normally (no After the “injury,” vessel growth can resume normally (no ROP), or (for unknown reasons), the primitive vessels pile-up ROP), or (for unknown reasons), the primitive vessels pile-up within the retina, growing without forward progress and within the retina, growing without forward progress and forming a ridge of tissue.forming a ridge of tissue.


The retina anterior to this line does not have an adequate The retina anterior to this line does not have an adequate oxygen supply, and probably exudes chemical signals that oxygen supply, and probably exudes chemical signals that stimulate new vessel growth. As more new vessels grow in stimulate new vessel growth. As more new vessels grow in response to the chemical signals, they form arterio-venous response to the chemical signals, they form arterio-venous shunts at the location of the barrier on the surface of the shunts at the location of the barrier on the surface of the retina. This shunt gradually enlarges, becoming thicker and retina. This shunt gradually enlarges, becoming thicker and more elevated. The new vessels are accompanied by more elevated. The new vessels are accompanied by fibroblasts, which produce fibrous scar tissue. fibroblasts, which produce fibrous scar tissue.

When this scar tissue contracts, it pulls on the retina and When this scar tissue contracts, it pulls on the retina and produces a traction retinal detachmentproduces a traction retinal detachment..


Until completely vascularized, vasculogenesis is highly Until completely vascularized, vasculogenesis is highly

vulnerable to any sort of insult or stress, including vulnerable to any sort of insult or stress, including

medications, high levels of oxygen, and variations in medications, high levels of oxygen, and variations in

light and temperature.light and temperature.

ROP - Risk FactorsROP - Risk Factors

Gestational age and low birth weightGestational age and low birth weight

Supplemental oxygenSupplemental oxygen

Vitamin E deficiencyVitamin E deficiency

Race (increased in Caucasians)Race (increased in Caucasians)

SurfactantSurfactant

Light levelsLight levels

Multiple birthsMultiple births

Transport after deliveryTransport after delivery

ROP - Risk FactorsROP - Risk Factors

OTHER OTHER IndomethacinIndomethacinElevated blood carbon dioxide levels Elevated blood carbon dioxide levels Anemia Anemia Blood transfusions Blood transfusions IVHIVHRDS RDS Chronic hypoxia in utero Chronic hypoxia in utero Multiple spells of apnea or bradycardia Multiple spells of apnea or bradycardia Mechanical ventilation Mechanical ventilation Seizures Seizures

ROP - ClassificationROP - Classification

1984 and 1987 International Classification of ROP:1984 and 1987 International Classification of ROP:

•3 Zones (location)3 Zones (location)

•Clock hours (extent)Clock hours (extent)

•Stages 1 through 5Stages 1 through 5

•Plus DiseasePlus Disease

IIII

IIIIIIIIII

MaculaMacula

Optic discOptic disc

33 99

1212 1212

33

6666

99

Right eyeRight eye Left eyeLeft eye

Ora Ora serrataserrata


IIIIII IIIIII


Stage 1Stage 1 - demarcation line - demarcation linebetween the normal retinabetween the normal retinanearer the optic nerve (onnearer the optic nerve (onthe left), and the non-the left), and the non-vascularizedvascularized retina (on the retina (on theright).right).

Multiple small abnormallyMultiple small abnormallybranching vessels canbranching vessels cansometimes be seen leadingsometimes be seen leadinginto the demarcation line.into the demarcation line.

Stage 1Stage 1. Demarcation line. Demarcation linebetween the normal retina between the normal retina (left) and the non-vascularized(left) and the non-vascularizedretina (right). retina (right).

Multiple small abnormallyMultiple small abnormallybraching vessels can sometimesbraching vessels can sometimesbe seen leading into the be seen leading into the demarcation line.demarcation line.


Stage 2Stage 2 - ridge (R) of scar - ridge (R) of scar tissue and new vessels in tissue and new vessels in place of the demarcation line. place of the demarcation line. The white line now has width The white line now has width and height, and occupies and height, and occupies some volume. some volume.

Small tufts of new vessels Small tufts of new vessels ("popcorn vessels") may ("popcorn vessels") may appear posterior to the ridge appear posterior to the ridge (arrowhead).(arrowhead).


Stage 3Stage 3 - Increased size of - Increased size of the vascular ridge (between the vascular ridge (between the arrowheads), with the arrowheads), with growth of fibrovascular growth of fibrovascular tissue on the ridge and tissue on the ridge and extending out into the extending out into the vitreous. vitreous.

Fibrous scar tissue is Fibrous scar tissue is beginning to form in this beginning to form in this stage, with attachments stage, with attachments between the vitreous gel and between the vitreous gel and the ridge.the ridge.


Stage 4Stage 4 - Partial retinal detachment. - Partial retinal detachment.

Stage 4A - detachment does not include the macula, Stage 4A - detachment does not include the macula, and the vision may be good. and the vision may be good.

In Stage 4B - macula is detached, and the visual In Stage 4B - macula is detached, and the visual potential is markedly decreased.potential is markedly decreased.

Stage 5Stage 5 - Complete retinal detachment. - Complete retinal detachment.


Plus diseasePlus disease - engorgement and - engorgement and tortuosity of the blood vessels tortuosity of the blood vessels near the optic nerve. near the optic nerve.

Also includes growth and dilation Also includes growth and dilation of abnormal blood vessels on the of abnormal blood vessels on the surface of the iris, rigidity of the surface of the iris, rigidity of the iris, and vitreous haze (exudate iris, and vitreous haze (exudate along the retinal vessels). along the retinal vessels).

Can accompany any stage, but Can accompany any stage, but indicates greater likelihood of indicates greater likelihood of progression to Stage 3 (or progression to Stage 3 (or greater).greater).


Rush DiseaseRush Disease::

Plus disease + Zone I ROPPlus disease + Zone I ROP

Progression occuring in days, rather than weeks.Progression occuring in days, rather than weeks.

Increased likelihood of progression to retinal detachmentIncreased likelihood of progression to retinal detachmentif left untreated>if left untreated>

•Zone I, any stageZone I, any stage

•Zone II, “plus disease” with stage 1, 2Zone II, “plus disease” with stage 1, 2

Pre-threshold ROPPre-threshold ROP

Threshold ROPThreshold ROP

ROP with 50% likelihood of progression to retinalROP with 50% likelihood of progression to retinaldetachement if left untreated>detachement if left untreated>

•Stage 3 with 5 continuous clock hours orStage 3 with 5 continuous clock hours or 8 cumulative clock hours with plus disease8 cumulative clock hours with plus disease

ROP - ManagementROP - Management

PREVENTION - PREVENTION - Prevent preterm labor.Prevent preterm labor.

(Optimal) minimum use of oxygen.(Optimal) minimum use of oxygen.

Prevention of complications.Prevention of complications.


Screening: In our NICU, all infants Screening: In our NICU, all infants <34 wks gestational age AND <1800 g <34 wks gestational age AND <1800 g birthweight are screened between 4-6 birthweight are screened between 4-6 weeks of age.weeks of age.


CRYOTHERAPY CRYOTHERAPY

For threshold ROP (stage 3 in at least 5 clock hours with plus For threshold ROP (stage 3 in at least 5 clock hours with plus disease)disease)

Freezing the sclera with cold probe. Freezing the sclera with cold probe.

Multiple applications are done to the entire avascular area Multiple applications are done to the entire avascular area anterior to the neovascular ridge. anterior to the neovascular ridge.

Treatment of the ridge itself is avoided, since the ridge tends to Treatment of the ridge itself is avoided, since the ridge tends to bleed and cause vitreous hemorrhage if frozen.bleed and cause vitreous hemorrhage if frozen.

Procedure is painful and done under general anesthesia.Procedure is painful and done under general anesthesia.

Complications: anesthesia problems; eyelid and conjunctivae Complications: anesthesia problems; eyelid and conjunctivae edemaedema


LASER PHOTOCOAGULATIONLASER PHOTOCOAGULATION Laser treatment for ROP is similar to cryotherapy. The laser Laser treatment for ROP is similar to cryotherapy. The laser

spot size is smaller than a spot of cryotherapy. Usually 600-spot size is smaller than a spot of cryotherapy. Usually 600-1000 spots of laser as compared to 30-50 spots of cryotherapy 1000 spots of laser as compared to 30-50 spots of cryotherapy needed. needed.

Laser is a direct treatment of the retina and its underlying Laser is a direct treatment of the retina and its underlying tissue instead of the entire thickness of the eye wall like in tissue instead of the entire thickness of the eye wall like in cryotherapy. cryotherapy.

Most ophthalmologists treating ROP are now using laser.Most ophthalmologists treating ROP are now using laser.


SCLERAL BUCKLESCLERAL BUCKLEFor shallow retinal detachment - placing a silicone band around For shallow retinal detachment - placing a silicone band around the equator of the eye to relieves the traction of the vitreous gel.the equator of the eye to relieves the traction of the vitreous gel.

VITRECTOMYVITRECTOMYFor complete retinal detachment -several small incisions into the For complete retinal detachment -several small incisions into the eye with removal and replacement of the vitreous gel with a saline eye with removal and replacement of the vitreous gel with a saline solution. After the vitreous has been removed, the scar tissue on solution. After the vitreous has been removed, the scar tissue on the retina can be peeled or cut away, allowing the retina to relax the retina can be peeled or cut away, allowing the retina to relax and lay back down against the eye wall and to re-attached. The and lay back down against the eye wall and to re-attached. The success rate ranges from 25% to 50% of patients undergoing success rate ranges from 25% to 50% of patients undergoing surgery. The functional success rate is significantly lower.surgery. The functional success rate is significantly lower.

ROP - ComplicationsROP - Complications

RETINAL DRAGGING AND FOLDS -RETINAL DRAGGING AND FOLDS -Neovascular tissue may heal, but a high risk that it will Neovascular tissue may heal, but a high risk that it will contract and form a scar (“cicatrix”) that pulls and contract and form a scar (“cicatrix”) that pulls and distorts the retina. distorts the retina.

The traction may drag the retina over the inside wall The traction may drag the retina over the inside wall of the eye.of the eye.

May result in markedly decreased vision.May result in markedly decreased vision.

ROP - ComplicationsROP - Complications

DraggingDragging - yellow/white - yellow/white optic nerve head in the optic nerve head in the center. The retinal vessels center. The retinal vessels coming from the optic nerve coming from the optic nerve are dragged in the direction are dragged in the direction of the arrow by scar tissue of the arrow by scar tissue (out of picture on the right (out of picture on the right side). The macula, which side). The macula, which should be off the left edge of should be off the left edge of this photograph, is visible as a this photograph, is visible as a subtle dark area about one subtle dark area about one disc diameter to the left of the disc diameter to the left of the disc.disc.

Clinical CourseClinical Course

•Most commonly, onset in Zone 2, slower progression; partial Most commonly, onset in Zone 2, slower progression; partial cicatrix; if onset in Zone 3, good prognosis for full recovery.cicatrix; if onset in Zone 3, good prognosis for full recovery.

•May take up to one year to stabilize, usually outcome May take up to one year to stabilize, usually outcome apparent by 3 months of age.apparent by 3 months of age.

•Mild ROP (Stage 1 or 2 without plus) and heals withoutMild ROP (Stage 1 or 2 without plus) and heals without a residual cicatrix (retinal scar)> may have higher incidencea residual cicatrix (retinal scar)> may have higher incidence of myopia, strabismus, amblyopiaof myopia, strabismus, amblyopia

•Threshold ROP with residual cicatrix> severe myopia, Threshold ROP with residual cicatrix> severe myopia, strabismus, amblyopia, retinal detachments as adultsstrabismus, amblyopia, retinal detachments as adults

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Retinopathy Of Prematurity Sigal Peter-Wohl MD Mark Kadrofske MD PhD