The document provides an overview of various vitreous and retinal conditions, including retinoblastoma, PHPV, Best disease, Coats disease, retinopathy of prematurity, Stargardt's disease, juvenile retinoschisis, and familial exudative vitreoretinopathy. It details the clinical features, pathophysiology, diagnostics, and management strategies for these disorders, highlighting their genetic and developmental aspects. The document serves as a comprehensive guide for understanding these complex eye conditions, particularly in pediatric patients.

1. VITREOUS AND RETINA

2. OVERVIEW
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
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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.

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

9. DIFFERENTIAL DIAGNOSIS

10. INVESTIGATIONS
 Fundus Fluorescein Angiography
 B Scan
 MRI
 CT-Scan
 Genetic counselling
 Complete blood count

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

14. CLINICAL FEATURES
 Strabismus
 Nystagmus
 Amblyopia
 Leukocoria
 Posterior polar Cataract
 RD

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

17. MANAGEMENT
 Visual rehabilitation – aphakia contact lens and amblyopia therapy
 Lensectomy
 Anterior or total vitrectomy

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

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

27. CLASSIFICATION
Stage 1
Retinal telangiectasia only
Stage 2
Telangiectasia and exudation
1.Extrafoveal exudation
2.Foveal exudation

28. Stage 3
Exudative RD
1.Subtotal detachment
a. extrafoveal
b. foveal
2.Total retinal detachment

29. Stage 4
Total retinal detachment and glaucoma
Stage 5
Advanced end stage disease

30. DIAGNOSIS
 Birth history
 Medical history ROP, Retinoblastoma
 Family history
 Slit lamp examination – congenital cataract , PHPV
 Characteristics ophthalmoscopic feature
 Fluorescein angiography
 CT
 MRI

31. Secondary complications
1.Rubeosis iridis
2.Neovascular glaucoma
3.Cataract
4.Uveitis

32. Differential diagnosis
1.Retinoblastoma
2.PHPV
3.ROP
4.Congenital cataract
5.Norrie’s disease

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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35. PATHOPHYSIOLOGY
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36. SYMPTOMS AND SIGNS
Nystagmus
White
reflex -
leukocoria
Strabismus Amblyopia
Not
responding
to light
Severe
myopia
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37. ZONES
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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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44. RISK FACTORS
 Toxic agents
• Injury
• Infection
• Exposure
Unprotected prolonged exposure to light
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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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50. FFA
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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.
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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.
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ERG – Negative
waveform in combined
response

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
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FAMILIAL EXUDATIVE VITREORETINOPATHY - AMERICAN ACADEMY OF OPHTHALMOLOGY-
OPHTHALMIC PEARLS
61
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

62. SYMPTOMS
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HTTPS://WWW.ASRS.ORG/PATIENTS/RETINAL-DISEASES/15/FAMILIAL-EXUDATIVE-
VITREORETINOPATHY
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Retinal
detachment
Vision
loss/blindness
leukocoria
Strabismus,
Amblyopia

63. SIGNS
STAGES
Peripheral
vascularity
Peripheral
vascular
tortuosity and
telangiectasia
Tractional/rhe
gmatogenous
macula
sparing RD
With or
without
exudation
Macular
involving
bilateral
Macular
involving
bilateral, often
asymmetric
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64. CLASSIFICATION
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FAMILIAL EXUDATIVE VITREORETINOPATHY - AMERICAN ACADEMY OF OPHTHALMOLOGY-
OPHTHALMIC PEARLS 64

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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

67. THANK YOU
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