Bilateral Eviscerations-Retinopathy of Prematurity Dr Caroline Graham Stoke Mandeville Hospital Aylesbury

Clinical History 24 year old female Traveller-limited history available Born 15 weeks prematurely Blind since birth

Clinical Summary Small eyeballs Enophthalmos Hypotonia Corneal scarring with band keratopathy and neovascularisation Bilateral, painful, phthisical eyes therefore bilateral eviscerations Non-functioning pituitary adenoma;no treatment

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

Left eye

Left eye

Left eye

Left eye

Left eye

Left eye

Left eye

Right eye

Right eye

Right eye

Right eye

Right eye

Summary of histology Left Cornea-irregular thickness, neovascularisation, amyloid Lens-calcified, wrinkled capsule Massive gliosis and calcification Drusen

Summary of histology Right Cornea-irregular thickness, band keratopathy, neovascularisation Lens-calcified and ossified with wrinkled capsule Gliosis, calcification, ossification

Summary Mostly non-specific changes of phthisis bulbi but in keeping with ROP ie no normal surviving retina, gliosis, drusen Amyloid is of interest-I think secondary to damaged eye but amyloid can be associated with ROP. Any ideas from the floor?

Retinopathy of Prematurity Vasoproliferative retinopathy Occurs in infants with an immature, incompletely vascularised retina Ranges from minimal sequelae which do not affect vision to bilateral, irreversible blindness

Retinal vascularisation Retinal vascularisation begins at about the 4th month of gestation with a vasculogenic wave Vascularisation reaches the nasal periphery by the 8th month of gestation and the temporal periphery by about 1 month post-term ROP develops at the interface between the vascularised retina and non-vascularised periphery

Risk factors for ROP Low birthweight ROP develops in 32% of infants with a birthweight of 1000 grams or less. Incidence falls to 7% if the birthweight is between 1001 and 1500 grams

Risk factors for ROP Retinal maturity The less well developed the retinal vasculature the more severe is the ROP Oxygen and angiogenic growth factors Oxygen tension causes capillary obliteration and vascular endothelial death in the immature retina Severity of ROP is related to the duration and amount of oxygen exposure Subsequent exposure to normal levels of oxygen results in opening of the vascular network and the hypoxic retina produces GFs

Risk factors for ROP ROP can occur in infants who are full term or who have not received oxygen therapy ?in utero injury to the genetic factors controlling vascularisation Can occur in full term infants because temporal retina not fully vascularised until 8 weeks after birth and therefore susceptible to damage

Stages of ROP Stage 1 Demarcation line A thin, tortuous grey-white line develops between the vascularised and avascular retina

Stages of ROP Stage 2 Ridge The demarcation lines becomes an elevated ridge of tissue Appears pink because of the formation of capillaries seen as abnormally branched vascular tufts

Stages of ROP Stage 3 Ridge with extraretinal fibrovascular proliferation Proliferating fibrovascular tissue breaks through the ILM and erupts onto the retinal surface and vitreous Retinal blood vessels posterior to the demarcation line become dilated and tortuous and there are retinal and vitreous haemorrhages Mild, moderate and severe forms

Stages of ROP Stage 4 Subtotal retinal detachment Extraretinal proliferation causes tractional retinal detachment Starts at periphery and spreads centrally

Stages of ROP Stage 5 Total retinal detachment In extreme cases the retina is totally detached and pulled into folds Together with the extraretinal tissue is drawn forward to lie against the lens (retrolental fibroplasia)

Clinical Course ROP usually undergoes complete regression if the stage is less than 2+ Sign of regression is the growth of vessels peripheral to the ridge Later stages associated with abnormal ocular growth; myopia; retinal pigmentation; dragging of the retina; retinal holes, folds, detachment; glaucoma; synechiae; haemorrhage; scarring; fibrosis; phthisis bulbi

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

Treatment Laser Vitrectomy for removal of retrolental mass

Molecular stuff VEGF – it’s complicated Insulin growth factor I (IGF-I). Hellstrom hypothesized that IGF-I plays a role in ROP

Thank you Miss Ramona Khooshabeh Luciane & Richard