Bilateral Bilateral Eviscerations-Eviscerations-Retinopathy of Retinopathy of PrematurityPrematurity

Dr Caroline GrahamDr Caroline Graham

Stoke Mandeville HospitalStoke Mandeville Hospital

Aylesbury Aylesbury

Clinical HistoryClinical History

24 year old female24 year old female Traveller-limited history availableTraveller-limited history available Born 15 weeks prematurelyBorn 15 weeks prematurely Blind since birthBlind since birth

Clinical SummaryClinical Summary

Small eyeballs Small eyeballs EnophthalmosEnophthalmos HypotoniaHypotonia Corneal scarring with band Corneal scarring with band

keratopathy and neovascularisation keratopathy and neovascularisation Bilateral, painful, phthisical eyes Bilateral, painful, phthisical eyes

therefore bilateral eviscerationstherefore bilateral eviscerations Non-functioning pituitary adenoma;no Non-functioning pituitary adenoma;no

treatmenttreatment

Macroscopic Macroscopic appearanceappearance LeftLeft:cornea 15 mm diameter with :cornea 15 mm diameter with

central opacity and some white central opacity and some white tissue 15 mm diametertissue 15 mm diameter

Right:Right: cornea 15 x 11 mm with a cornea 15 x 11 mm with a central and peripheral opacity central and peripheral opacity and some firm haemmorhagic and some firm haemmorhagic tissue, apparently calcified, 12 tissue, apparently calcified, 12 mm in diameter.mm in diameter.

Left eyeLeft eye

Left eyeLeft eye

Left eyeLeft eye

Left eyeLeft eye

Left eyeLeft eye

Left eyeLeft eye

Left eyeLeft eye

Right eyeRight eye

Right eyeRight eye

Right eyeRight eye

Right eyeRight eye

Right eyeRight eye

Summary of histologySummary of histology

LeftLeft Cornea-irregular thickness, Cornea-irregular thickness,

neovascularisation, amyloidneovascularisation, amyloid Lens-calcified, wrinkled capsuleLens-calcified, wrinkled capsule Massive gliosis and calcificationMassive gliosis and calcification DrusenDrusen

Summary of histologySummary of histology

RightRight Cornea-irregular thickness, band Cornea-irregular thickness, band

keratopathy, neovascularisationkeratopathy, neovascularisation Lens-calcified and ossified with Lens-calcified and ossified with

wrinkled capsulewrinkled capsule Gliosis, calcification, ossificationGliosis, calcification, ossification

SummarySummary

Mostly non-specific changes of Mostly non-specific changes of phthisis bulbi but in keeping with phthisis bulbi but in keeping with ROP ie no normal surviving retina, ROP ie no normal surviving retina, gliosis, drusengliosis, drusen

Amyloid is of interest-I think Amyloid is of interest-I think secondary to damaged eye but secondary to damaged eye but amyloid can be associated with ROP. amyloid can be associated with ROP.

Any ideas from the floor?Any ideas from the floor?

Retinopathy of Retinopathy of PrematurityPrematurity Vasoproliferative retinopathyVasoproliferative retinopathy Occurs in infants with an Occurs in infants with an

immature, incompletely immature, incompletely vascularised retinavascularised retina

Ranges from minimal sequelae Ranges from minimal sequelae which do not affect vision to which do not affect vision to bilateral, irreversible blindnessbilateral, irreversible blindness

Retinal vascularisationRetinal vascularisation

Retinal vascularisation begins at about Retinal vascularisation begins at about the 4the 4thth month of gestation with a month of gestation with a vasculogenic wavevasculogenic wave

Vascularisation reaches the nasal Vascularisation reaches the nasal periphery by the 8periphery by the 8thth month of gestation month of gestation and the temporal periphery by about 1 and the temporal periphery by about 1 month post-termmonth post-term

ROP develops at the interface between ROP develops at the interface between the vascularised retina and non-the vascularised retina and non-vascularised peripheryvascularised periphery

Risk factors for ROPRisk factors for ROP

Low birthweight Low birthweight ROP develops in 32% of infants ROP develops in 32% of infants

with a birthweight of 1000 grams with a birthweight of 1000 grams or less.or less.

Incidence falls to 7% if the Incidence falls to 7% if the birthweight is between 1001 and birthweight is between 1001 and 1500 grams1500 grams

Risk factors for ROPRisk factors for ROP

Retinal maturityRetinal maturity The less well developed the retinal vasculature The less well developed the retinal vasculature

the more severe is the ROPthe more severe is the ROPOxygen and angiogenic growth factorsOxygen and angiogenic growth factors Oxygen tension causes capillary obliteration and Oxygen tension causes capillary obliteration and

vascular endothelial death in the immature vascular endothelial death in the immature retinaretina

Severity of ROP is related to the duration and Severity of ROP is related to the duration and amount of oxygen exposureamount of oxygen exposure

Subsequent exposure to normal levels of oxygen Subsequent exposure to normal levels of oxygen results in opening of the vascular network and results in opening of the vascular network and the hypoxic retina produces GFs the hypoxic retina produces GFs

Risk factors for ROPRisk factors for ROP

ROP can occur in infants who are full ROP can occur in infants who are full term or who have not received oxygen term or who have not received oxygen therapy therapy

?in utero injury to the genetic factors ?in utero injury to the genetic factors controlling vascularisation controlling vascularisation

Can occur in full term infants because Can occur in full term infants because temporal retina not fully vascularised temporal retina not fully vascularised until 8 weeks after birth and therefore until 8 weeks after birth and therefore susceptible to damagesusceptible to damage

Stages of ROPStages of ROP

Stage 1 Demarcation lineStage 1 Demarcation line A thin, tortuous grey-white line A thin, tortuous grey-white line

develops between the develops between the vascularised and avascular retinavascularised and avascular retina

Stages of ROPStages of ROP

Stage 2 Ridge Stage 2 Ridge The demarcation lines becomes The demarcation lines becomes

an elevated ridge of tissuean elevated ridge of tissue Appears pink because of the Appears pink because of the

formation of capillaries seen as formation of capillaries seen as abnormally branched vascular abnormally branched vascular tuftstufts

Stages of ROPStages of ROP

Stage 3 Ridge with extraretinal fibrovascular Stage 3 Ridge with extraretinal fibrovascular proliferationproliferation

Proliferating fibrovascular tissue breaks Proliferating fibrovascular tissue breaks through the ILM and erupts onto the through the ILM and erupts onto the retinal surface and vitreousretinal surface and vitreous

Retinal blood vessels posterior to the Retinal blood vessels posterior to the demarcation line become dilated and demarcation line become dilated and tortuous and there are retinal and vitreous tortuous and there are retinal and vitreous haemorrhageshaemorrhages

Mild, moderate and severe formsMild, moderate and severe forms

Stages of ROPStages of ROP

Stage 4 Subtotal retinal Stage 4 Subtotal retinal detachmentdetachment

Extraretinal proliferation causes Extraretinal proliferation causes tractional retinal detachmenttractional retinal detachment

Starts at periphery and spreads Starts at periphery and spreads centrallycentrally

Stages of ROPStages of ROP

Stage 5 Total retinal detachmentStage 5 Total retinal detachment In extreme cases the retina is totally In extreme cases the retina is totally

detached and pulled into folds detached and pulled into folds Together with the extraretinal tissue Together with the extraretinal tissue

is drawn forward to lie against the is drawn forward to lie against the lens (retrolental fibroplasia)lens (retrolental fibroplasia)

Clinical CourseClinical Course

ROP usually undergoes complete ROP usually undergoes complete regression if the stage is less than 2+regression if the stage is less than 2+

Sign of regression is the growth of vessels Sign of regression is the growth of vessels peripheral to the ridgeperipheral to the ridge

Later stages associated with abnormal Later stages associated with abnormal ocular growth; myopia; retinal ocular growth; myopia; retinal pigmentation; dragging of the retina; pigmentation; dragging of the retina; retinal holes, folds, detachment; retinal holes, folds, detachment; glaucoma; synechiae; haemorrhage; glaucoma; synechiae; haemorrhage; scarring; fibrosis; phthisis bulbi scarring; fibrosis; phthisis bulbi

PreventionPrevention

Titration of oxygen levels to level Titration of oxygen levels to level at which systemic complications at which systemic complications caused by hypoxia and ocular caused by hypoxia and ocular complications caused by complications caused by hyperoxia might be avoidedhyperoxia might be avoided

TreatmentTreatment

LaserLaser Vitrectomy for removal of Vitrectomy for removal of

retrolental massretrolental mass

Molecular stuffMolecular stuff

VEGF – it’s complicatedVEGF – it’s complicated Insulin growth factor I (IGF-I). Insulin growth factor I (IGF-I).

Hellstrom hypothesized that IGF-I Hellstrom hypothesized that IGF-I plays a role in ROPplays a role in ROP

Thank you Thank you

Miss Ramona KhooshabehMiss Ramona Khooshabeh Luciane & RichardLuciane & Richard