This ppt explains about the various pediatric ocular diseases of retina and vitreous:
1.Retinoblastoma
2.Persistent hyperplastic primary vitreous (PHPV)
3.Best disease
4.Coats disease
5.Retinopathy of prematurity
6.Stargardts disease
7.Juvenile retinoschisis
8.Familial exudative vitreoretinopathy
3. RETINOBLASTOMA
Rare condition
Most common primary intraocular tumor in children.
Abnormal red reflex
Life- threatening disorders
Incidence of 1: 18,000-30,000 live births
Common in both genders
No race predilection
Unilateral/bilateral
4. ETIOLOGY
Retinoblastoma tumors can be either heritable and associated with a germline mutation of the
RB1 gene, or non-heritable.
Heritable mutations typically present in the 1st year of life with bilateral disease.
Non-heritable form typically presents slightly later and is primarily unilateral.
5.
6. Reese Ellsworth’s classification
Group A Solitary tumor, <4 disc diameters in size, at or posterior to the equator of the eye
Multiple tumors, none >4 disc diameters in size, all at or behind the equator.
Group B Solitary tumor, 4 to 10 disc diameters in size, at or behind the equator.
Multiple tumors, 4 to 10 disc diameters in size, behind the equator
Group C Any lesion anterior to the equator.
Solitary tumors >10 disc diameters behind the equator.
Group D Multiple tumors, some >10 disc diameters in size.
Any lesion extending anteriorly to the ora serrata (the serrated junction between the retina
and the ciliary body).
Group E Massive tumors involving over half the retina.
Vitreous seeding.
7. CLINICAL FEATURES
Symptoms:
Usually, no symptoms occur; however, redness and irritation of the eye and eyelids may occur
in advanced cases.
Vision may be decreased
8. Signs:
Leukocoria
Exotropia or esotropia
White dome-shaped mass that is endophytic (grows from the retina into the vitreous cavity),
exophytic (grows from the retina into the subretinal space), or diffusely infiltrating
Dilated and tortuous retinal arteries and veins feeding the tumor
Vitreous seeds
Iris nodules
Clear lens
11. MANAGEMENT
Small tumors - laser treatment, cryotherapy, and radioactive plaque treatment, combined with
chemotherapy in some cases, may restore vision or save the eye.
Orbital extension - radiation therapy and chemotherapy
Distant metastases - prognosis is worse but chemotherapy and radiation therapy have a
significant success rate.
Advanced ocular tumors - removal of the eye (enucleation) is performed.
12. PERSISTENT HYPERPLASTIC PRIMARY
VITREOUS (PHPV)
PHPV is a congenital anomaly in which the primary vitreous fails to regress in utero
High vascular mesenchymal tissues nurtures the developing lens during intrauterine life
In PHPV the mesenchymal tissues forms a mass behind the lens
13. PATHOPHYSIOLOGY
During the period of embryonic development of the eye the compartment between the retina
and crystalline lens contains vascular system (hyaloid artery) that provides nutrient are
supposed to regress in the 3rd trimester
Failure of fetal vascular to regress over due to somatic mutation
15. DIAGNOSIS
B-SCAN ,MRI, a cone shape retinolental density is a characteristic finding on PHPV on imaging
studies
Fluorescein angiography with silt lamp shows location of abnormal vasculature the brittle star
configuration
Peripheral retinal capillary non perfusion may also be noted in ROP
16. COMPLICATION
Untreated PHPV results in glaucoma and phthisis bulbi
Recurrent hyphema in angle-Glaucoma
PHPV eyes with myopia have less media opacity, normal corneal diameters are detected late
and have good visual prognosis
18. BEST DISEASE
AD
Mutation of BEST1-Bestrophin 1 (transmembrane protein)
Located predominantly at the basolateral membrane of the RPE
Characteristic presentation is by bilateral fundus changes of egg-yolk appearance
RPE is primarily affected
Symptomless in early stages-gradual decrease in advance stages
19. PATHOPHYSIOLOGY
There is deposition of lipofuscin within the RPE, the subretinal space, and the photoreceptor
zone
A break/disturbance in the RPE/Bruch's membrane results in a late complication of a choroidal
neovascular membrane (CNVM)
20. STAGES
Normal
Pre Vitelli form stage- yellowish dot at fovea
Vitelli form stage- blister on your macula
area which looks similar to an egg yolk, fluid cyst
Psuedohypopyon- yellow matter which causes the egg yolk- like blister can
breakthrough a layer under your retina.
Vitellirupture- lesion begins to break up and can cause damage to some of
the cells in the layers of your retina.
Atrophic stage- yellow material withdraw and disappear, scarring, CNVM
21.
22.
23. EOG
The Arden ratio (light–dark ratio) is typically less than 1.5 and often near 1.1
24. COATS DISEASE
Unilateral 90%
Young boys <20
Peak incidence at 6 to 8 years
No racial,genetic or familial predisposition
1st described by George coats in 1908
Leaking telangiectatic and aneurysmal vessels with intraretinal and subretinal exudation
25. ETIOLOGY
Unknown
If a female with unilateral coats disease gave birth to a son with norrie disease
Somatic mutation in NPD gene
Deficiency of norrin
Abnormal retinal vasulogenesis
26. PATHOPHYSIOLOGY
Degeneration of abnormal endothelial cells
Telangiectesia – saccular or fusiform aneurysm
Loss of blood retinal barrier – exudation ( rich in cholesterol, macrophages, few erythrocytes and min
hemosiderin)
Massive exudation – exudative RD
Fibrous submacular nodules (50%) – proliferation and metaplasia in RPE
33. MANAGEMENT
AIM – Eliminate abnormal retinal vessels
To know about the severity and stages of disease and location of lesion
1.Laser photocoagulation
2.Cryotherapy
Surgery
Pars plana vitrectomy – removal of tractional / epiretinal membrane
34. RETINOPATHY OF PREMATURITY (ROP)
Affects premature low birth weight infants (<37 weeks or 8.5 months)
Early exposure to high ambient oxygen concentrations – key risk
In-complete development of retinal circulation, leading to growth of abnormal new blood
vessels
NORMAL RETINAL DEVELOPMENT
Retina has no blood
vessels until the
fourth month of
gestation
Where vascular
complexes grow from
optic disc hyaloid
vessels towards the
periphery
Nasal retina –after 8
months of gestation
and temporal
periphery at or by 1
month after delivery
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38. STAGES OF ROP – based on severity of
disease
Stage 1: Demarcation line
Stage 2: Ridge present
Stage 3: Fibro vascular proliferation
Stage 4: Partial retinal detachment
Stage 5: Total retinal detachment
Plus disease refers to presence of tortuous dilated vessels at posterior pole with any stage of ROP.
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40. PLUS DISEASE
‘Plus’ disease - dilatation and
tortuosity of blood vessels involving at
least two quadrants of the posterior
fundus with any stage of ROP.
Other features include failure of the
pupil to dilate and vitreous haze
Iris neovascularisation
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41. TREATMENT
Objectives:ablation of avascular retina to
• ↓ O2 demand
• ↓ production of VEGF
• induce a regression of the ROP
CRYO-THERAPY & PHOTOCOAGULATION (LASER)
ANTI VEGF TREATMENT (Bevacizumab- Avastin)
INSULIN GROWTH FACTOR-1 (IGF-1)- enable child growth
POLYUNSATURATED FATTY ACIDS –nutritional supplements
PROPRANOLOL-prevent heart disease, HTN
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42. SURGICAL TREATMENT
Stage 1 and 2: Since spontaneous regression of disease occurs in 80 to 90% of cases, so only a
weekly examination is recommended.
Stage 3: Should be treated by cryo or laser to prevent progression and to achieve regression.
Stage 4: Scleral buckling is recommended in addition to cryo or laser therapy.
Stage 5: Vitrectomy needs to be carried out in this stage. Prognosis is poor.
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43. STARGARDTS DISEASE
Inherited disorder of retina.
Vision loss during childhood or adolescence.
AUTOSOMAL RECESSIVE disease.
Progressive damage/degeneration of macula.
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45. PATHOPHYSIOLOGY
Stargardt’s diseases the most inherited macular dystrophy in both adults and children's.
STGD1 has an autosomal recessive mode of inheritance associated with disease causing
mutation in the ABCA4 gene.
It is both clinically and genetically highly heterogeneous.
The disease is associated with accumulation of fluorescent lipofuscin pigments in cells of the
RPE.
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47. SYMPTOMS SIGNS
Slow loss of central vision in both eyes The fundus shows bull’s eye pattern
Gray black or hazy spots in central of their
vision
With or without yellowish flecks (fundus
flavimaculatus)
Takes longer time to adjust when moving light
to dark environment
On fundus autofluorescence (FAF), newer
flecks appear hyper autofluoresent
Sensitive to bright Fluorescein angiography may show dark
choroid
Color vision defect
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49. INVESTIGATIONS
FAF and OCT findings :Fundus
autofluorescence photograph
shows mottled areas of
hyperautofluorescence and
hypofluorescence,corresponding to
areas of lipofusin accumulation and
RPE atrophy.
SDOCT: Horizontal and vertical
sections through the fovea reveal
parafoveal disruption of outer
retinal layers.
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51. 10/24/2023
TANNA, P., STRAUSS, R. W., FUJINAMI, K., & MICHAELIDES, M. (2017). STARGARDT DISEASE:
CLINICAL FEATURES, MOLECULAR GENETICS, ANIMAL MODELS AND THERAPEUTIC OPTIONS. THE
BRITISH JOURNAL OF OPHTHALMOLOGY, 101(1), 25–30.
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52. TREATMENT
Dark glasses and hats when out in bright light to reduce the buildup of lipofuscin.
Cigarette smoking should be avoided.
Gene therapy provides hope for future treatment options.
10/24/2023
HTTPS://WWW.NEI.NIH.GOV/LEARN-ABOUT-EYE-HEALTH/EYE-CONDITIONS-AND-
DISEASES/STARGARDT-DISEASE
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53. JUVENILE RETINOSCHISIS
X-linked Retinoschisis, or X-Linked Juvenile Retinoschisis
Rare congenital disease of the retina caused by mutations in the RS1 gene, which encodes
retinoschisin, a protein involved in intercellular adhesion and likely retinal cellular organization.
X-linked retinoschisis has also been referred to as: juvenile retinoschisis, congenital
retinoschisis, juvenile macular degeneration/dystrophy, degenerative retinoschisis, and vitreous
veils of the retina.
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54. PATHOPHYSIOLOGY
X-linked retinoschisis is linked to mutations in RS1. The gene encodes a 224-amino acid protein
called retinoschisin, which is secreted by photoreceptors.
This protein is found throughout the retina, and is thought to be involved in cell-cell adhesion
and intercellular matrix retinal architecture development through interactions with αβ crystallin
and β2-laminin.
On histopathological examination, the splitting in X-linked retinoschisis occurs predominantly in
the nerve fiber layer.
Splitting of neurosensory retina
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55. SIGNS AND SYMPTOMS
Gradual decrease in vision
Poor vision due to foveal schisis
Peripheral schisis will cause RD and vitreous hemorrhage
Non-leaking fovea with cyst
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56. INVESTIGATIONS
Digital fundus photography: may help with examination of a child
Red-free illumination: may help to highlight the area of foveal schisis
Fundus autofluorescence: increased fundus autofluorescence helps to highlight areas of foveal
schisis
OCT: schisis in the superficial neural retina and thinning of the retina. Small cystic-like spaces
FFA: can differentiate foveoschisis from CME, which can show petaloid macular leakage
ffERG: reduced b-wave with preserved a-wave, “negative waveform”. the a-wave may be
reduced as the disease progresses.
10/24/2023
HTTPS://EYEWIKI.AAO.ORG/X-LINKED_RETINOSCHISIS
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59. TREATMENT
For those <10 years old: Annual evaluation by a pediatric ophthalmologist or retina specialist.
Patient education: Avoid head trauma and high-contact/impact sports due to the increased risk
of retinal detachment/Vitreous hemmorhage
Amblyopia
Genetic counseling: Female carriers have a 50% chance of passing the mutation. Male patients
should be counseled that they will pass the mutation to all daughters
For those with low vision: low vision aids
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60. FAMILIAL EXUDATIVE
VITREORETINOPATHY (FEVR)
Inherited vitreoretinal disorder characterized by incomplete or anomalous vascularization of
the peripheral retina
It is usually inherited as an autosomal dominant trait, but X-linked transmission also occurs
HISTORY: Unlike ROP, there is usually a family history of the disorder patients lack a history of
prematurity or oxygen supplementation
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61. PATHOPHYSIOLOGY
10/24/2023
FAMILIAL EXUDATIVE VITREORETINOPATHY - AMERICAN ACADEMY OF OPHTHALMOLOGY-
OPHTHALMIC PEARLS
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In normal development,
vasculogenesis begins
Angiogenesis Occurs
This process is mediated
by VEGF
Most genes associated
with FEVR affect
pathways - retinal
vasculature via
angiogenesis
The gene mutations in
FEVR lead to incomplete
or anomalous vascu-
larization of the
peripheral retina
66. TREATMENT
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Stage 1 can be managed with observation for signs of neovascularization
Stage 2 to 5, the goal is to prevent the progression and sequelae of neovascularization. Laser
photocoagulation and/or cryotherapy to address neovascularization are indicated in stage 2.
Anti-VEGF therapy may decrease hemorrhage and exudation
Surgical techniques include pars plana vitrectomy, scleral buckling, or a combination of both
with or without lensectomy for RD
Leucocoria – occur due to dense retrolenticular membrane or cataractous lens
Strabismus – present at birth or develop shortly
VA near normal
PHPV unilateral
Occasionally RD
A secondary glaucoma can also be produced from recurrent hyphema, which scars the outflow passageways in the angle. By removing the PHPV membrane and reducing the tractional forces applied to the ciliary body by the membrane, one can lessen the possibility of phthisis
With rehab useful vision can be obtained in the majority of patients with both anterior and posterior persistent fetal vasculature
Effective management of the anisometropic amblyopia requires motivated patient to ensure compliance with occulusive therapy as well as parents willing to attennumerous visit to eye specialists
Fundus fluorescein angiogram (FFA)- FFA is crucial to rule out choroidal neovascular membrane (CNVM) which shows fluorescence that increases in size and intensity with time
Shields et.al 2001 for selecting treatment and predicting outcome.
The retina has no blood vessels until the fourth month of gestation, when vascular complexes grow from optic disc hyaloid vessels towards the periphery. The nasal retina is normally fully vascularized after 8 months of gestation, the temporal periphery at or by 1 month after delivery.
Vascular endothelial growth factor (VEGF) is believed to play an important role in the vascularization process
Severity of ROP can be graded based on the location of vasculature.
Ora serrata is the junction between the choroid and ciliary body
Zone I is bounded by an imaginary circle, the radius of which is twice the distance from the disc to the centre of the macula.
• Zone II extends concentrically from the edge of zone I; its radius extends from the centre of the disc to the nasal ora serrata.
• Zone III consists of a residual temporal crescent anterior to zone II
Stage 1 (demarcation line) is a thin, flat, tortuous, grey-white line running roughly parallel with the ora serrata. It is more prominent in the temporal periphery. There is abnormal branching or ‘arcading’ of vessels leading up to the line
Stage 2 (ridge) arises in the region of the demarcation line. Blood vessels enter the ridge and small isolated neovascular tufts may be seen posterior to it
Stage 3 (extraretinal fibrovascular proliferation) extends from the ridge into the vitreous. The severity of stage 3 can be subdivided into mild, moderate and severe depending on the extent of extraretinal fibrous tissue infiltrating the vitreous.
Stage 4 (partial retinal detachment) The detachment is generally concave and circumferentially orientated. In progressive cases the fibrous tissue continues to contract and the detachment increases in height and extends anteriorly and posteriorly
Stage 5 refers to total retinal detachment
‘Plus’ disease signifies a tendency to progression and is characterized by dilatation and tortuosity of blood vessels involving at least two quadrants of the posterior fundus with any stage of ROP.
Whom to screen?
By gestational age: < 30 weeks
Birth weight: < 1500 g
1500 – 2000 g if unstable clinical course
Laser ablation of avascular peripheral retina (Fig. 13.52) has largely replaced cryotherapy because visual and anatomical outcomes are superior.
• Intravitreal anti-VEGF agents. Bevacizumab has been used for the treatment of ROP, but an optimal regimen is yet to be established.
Zone I disease is more likely to respond than zone II. Allowing retinal development to proceed normally without the destruction integral to laser treatment is a potential advantage. However, systemic complications and long-term effects in this age group are undetermined.
• Pars plana vitrectomy for tractional retinal detachment not involving the macula (stage 4A) can be performed successfully with respect to anatomical (90% success) and visual outcome. The visual outcome in stages 4B (e.g. 60%) and 5 (e.g. 20%) is typically disappointing even with successful anatomical reattachment
The OCT findings of patients with stargardts disease include decreased thickness of the retina, most notably in the foveolar. The OCT also reveals photoreceptor loss and extranuclear layer changes, as well as abnormalities in the RPE.
Silent choroid, Central ovoid area of dystrophy is seen as hyperfluorescent because of the transmission defects. “Silent choroids” is due to the presence of abnormal Lipofuscin like material, which gets deposited in the RPE layer in these patients
OCT: After adolescence, the cystic spaces may not be as evident because of flattening of cysts with increasing age. These cystic spaces occur predominantly in the nerve fiber layer although splitting can occur between other retinal layers as well. OCT can reveal areas of schisis that may not be visible on fundus examination.
Full-field electroretinogram (ffERG): electronegative (reduced b-wave with preserved a-wave, "negative waveform"). This is not diagnostic as the differential for electronegative ERG includes several other retinal disorders, the a-wave may be reduced as the disease progresses, and some affected individuals can have a technically normal ERG.
Genetic testing for mutations in the RS1 gene can confirm the diagnosis. Over 200 disease-causing mutations in the RS1 gene have been identified.
FFA:Non leaking schitic spaces, OCT: schsis
Amblyopia: Treat amblyopia, especially in cases of severe retinoschisis, hypermetropia, or following surgery for vitreous hemorrhage or retinal detachment.
Genetic counseling: male patients should be counseled that they will pass the mutation to all daughters (who will most likely be asymptomatic heterozygote carriers), but will not pass the mutation to sons. Female carriers have a 50% chance of passing the mutation - all sons who inherit the mutation will be affected, and daughters who inherit the mutation will most likely be asymptomatic carriers.
For those with low vision: Low vision aids (large-print textbooks), preferential seating in the front of the classroom, handouts with high contrast
Familial exudative vitreoretinopathy (FEVR) is an inherited vitreoretinal disorder characterized by incomplete or anomalous vascularization of the peripheral retina. The avascular peripheral retina leads to various degrees of retinal ischemia, which can cause neovascularization, vascular dragging, radial retinal folds, retinal exudates, vitreous hemorrhages, and tractional retinal detachments (RDs). About half of FEVR cases are associated with known genetic mutations, and the etiology is unknown in the remainder.
Incomplete vascularization of peripheral retina in FEVR is the result of developmental abnormalities.
In normal development, vasculogenesis begins when spindle-shaped mesenchymal precursor cells, migrating to the retina through the optic disc, differentiate into endothelial cells, which aggregate to form patent vessels that expand centrifugally. Next, angiogenesis occurs when sprouts of blood vessels emanate from the preexisting vascular framework, increasing the vascular density of the immature plexus and extending it peripherally. This process is mediated by vascular endothelial growth factor (VEGF) expressed by astrocytes in response to localized retinal hypoxia, which highlights the importance of VEGF in ocular vascularization.5
X-linked FEVR are associated with mutations in the NDP gene, which produces the norrin protein
Most genes associated with FEVR affect pathways regulating the development of the secondary embryonic retinal vasculature via angiogenesis. Thus, the gene mutations in FEVR lead to incomplete or anomalous vascularization of the peripheral retina. In normal development, hyaloid vasculature forms and then regresses prior to retinal vascular development, but persistent hyaloid vasculature due to failure of regression is sometimes seen in FEVR.
Vision loss may also occur as a result of abnormal leaking blood vessels (exudation), and a progressive shutdown of the finest blood vessels in the eye (capillary dropout) critical for the delivery of oxygen to the retinal cells.