Congenital Retinal Anomalies

EmbryologyNeural ectodermal cells first month of developmentGanglion cell layer first sixth week of gestationCones 5 monthsRods 7 monthsGrowth after birth too RBVitreous develops in 3 stages First 2-3 monthSecond and Tertiary 3-4 monthSupply from Hyaloid artery

EpidemiologyRare anomaliesDiseases With Specific Retinal Findings That Suggest a Diagnosis

Egg yolkBest disease LacunaeAicardi syndrome Cherry-red spotmetabolic diseases Retinal necrosis and hemorrhageCytomegalovirus Astrocytic hamartomaTuberous sclerosis

PathogenesisCongenital defects (e.g., coloboma), Vascular abnormalities (e.g., retinopathy of prematurity [ROP]),InfectionsTumors,Trauma, and Metabolic diseases

Clinical PresentationUnilateral abnormalities may be difficult to detect, because the children function well if the vision is good in the other eye. The vision loss may not be noticed until the child has a vision test or if the child occludes the normal eye Strabismus may develop in eyes with unilateral vision lossIn some lesions, such as retinoblastoma or large colobomas, an abnormality of the red reflex may be noted. If the vision loss is bilateral, decreased vision will usually be evident. In infants, significant bilateral vision loss initially manifests as nystagmus that develops within the first 2 to 3 months of life.

CONGENITALColobomaincomplete closure of the embryonic fissureinferonasal quadrant white defects, because the sclera is directly visible due to the absence of normal retina and retinal pigment epitheliumPrognosis Foveal involovementIsolated or may withsystemic disorders, such as CHARGE (Coloboma, Heart defects, Atresia choanae, Retardation of growth, Genitourinary anomalies, and Ear anomalies) syndrome. Not progressive. Difficult to treat.

Congenital Retinal FoldRare anomalies A fold of retinal tissue extends from the optic nerve to the retinal periphery, usually in the inferotemporal portion of the eyeMay be inherited in an autosomal dominant associated with marked vision loss, and are not amenable to treatment.

Persistent Fetal Vasculatureincomplete regression of the hyaloid blood vessel during embryological development

Aicardi SyndromeX-linked Distinctive retinal changes.Femalesmaternal spontaneous abortionsSystemic findings absence of the corpus callosum, developmental delay, and seizures. Retinal findingsmultiple round depigmented areas (lacunae), primarily in the posterior portion of the retina

AlbinismDecreased pigment (oculocutaneous albinism [OCA])Isolated to the eye (ocular albinism).Neonatal period with decreased vision and nystagmus. Decreased skin and hair pigment.Transillumination defects of the irisDecreased peripheral retinal pigmentation,Hypoplasia of the foveaVA Range : 20/100 - 20/200

Foveal HypoplasiaThe normal foveal reflex is missing and the retinal blood vessels are not organized around the fovea.The abnormal foveal anatomy causes decreased vision in patients with foveal hypoplasia. AlbinismAniridiaMay be suspected of having amblyopia or factitious visual loss unless the retina is carefully examined.

ABNORMALITIES OFVASCULAR DEVELOPMENT

Retinopathy of PrematurityAbnormal neovascular tissue develops. This tissue may proliferate and cause bleeding and traction, which can progress to retinal detachment. Major cause of morbidity in premature infants. The risk increases with decreasing birth weight and gestational age, occurring almost exclusively in infants born at 30 weeks gestation or less.

The presence of plus disease is a key indicator of risk. Plus disease describes increased tortuosity and dilation of the posterior blood vessels which reflects the abnormal retinal vascular development.

Stages1 - Demarcation line2 Elevated ridge at border of demarcation3 Elevated Ridge with abnormal blood vessels4 Partial Tractional Retinal Detachment5 Total Retinal Detachment ( closed funnel)

Treatment of ROP

Prevent retinal distortion and detachment by stopping the abnormal vascular activityThe presence of any plus disease or stage 3 disease in zone 1, or the presence of stages 2 or 3 and plus disease in zone 2The peripheral retina in patients with ROP produces vascular endothelial growth factor (VEGF), which stimulates the growth of abnormal vessels. Treatmentlaser or cryotherapy The goal is to decrease production of VEGF and induce regression of the abnormal vessels.Develop scars in the fovea after treatment, which may impair visual acuity If patients develop progressive retinal detachments, retinal surgery (such as vitrectomy) may be indicated. Visual Prognosis Poor

intraventricular hemorrhage

Other Disorders of PeripheralRetinal VascularizationNorrie disease. An X-linked disorder characterized by the retinal abnormalities, hearing loss, and developmental delay.

Familial exudative vitreoretinopathy (FEVR). An autosomal dominant disorder caused by mutation of the FEVR1 gene on chromosome 11

Incontinentia pigmenti. An X-linked disorder that is usually lethal in males. Affected patients develop bullous erythematous skin lesions in the neonatal period, followed by verrucous changes, and subsequently hyperpigmented macules. Developmental delay and dental changes occur in some patients. Approximately one-third of patients develop retinal changes similar to ROP. Many patients also develop cataracts.

Coats disease. An idiopathic disorder of retinal vasculature that occurs in older children.Unilateral. Peripheral abnormal telangiectatic retinal blood vessels proliferate and leak exudative fluid produce large collections of yellow subretinal fluid and retinal detachments

Von-Hippel-Lindau disease (VHL). An autosomal dominant disorder in which patients develop vascular tumors of the retina and central nervous system. Systemic manifestations include renal cell carcinoma, pheochromocytoma, and lesions in multiple other organs

Peripheral retinalangiomas

Sickle cell disease.Develop peripheral retinal abnormalities secondary to decreased vascular perfusion. Caused by arteriolar occlusion induced by sickling of the abnormal red blood cells. Patients with hemoglobin SC disease and sickle thalassemia have the highest risk of retinal complications. If untreated, this may progress and cause vitreous hemorrhage and retinal detachments.Laser treatment is used to treat these lesions

INFECTIOUS DISEASESHerpes Simplex VirusCongenital HSV is usually acquired during passage through the birth canal. systemic involvement, including the skin, central nervous, liver, lungs, and eyes. Ocular findings include conjunctivitis and keratitis. If the retina is involved, patients may develop massive retinal necrosis with marked visual loss. Treatment includes systemic medication, such as acyclovir.

Cytomegaloviruscommon congenital infection in humans.Asymptomatic. Systemic manifestations liver, hematological, hearing, and central nervous system abnormalities.Ophthalmic manifestations retinochoroiditis, which is characterized by focal areas of retinal necrosis and hemorrhages. Infants with systemic involvement and older immunocompromised children with CMV are usually treated with ganciclovir.

SyphilisCongenital syphilis may cause a wide variety of systemic and ocular problems. Ocular abnormalities may develop in infancy or later in childhood. Retinal involvement consists of chorioretinitis, which may appear similar to retinitis pigmentosa.

ToxoplasmosisToxoplasma gondii, an obligate intracellular parasite. Exposure to cats or through contaminated meat or drinking water. Congenital infections are associated with liver, spleen, central nervous system, and ocular involvement.

Characterized by inactive circumscribed pigmented retinal scars. If the lesions reactivate, focal areas of retinitis with inflammation and overlying vitritis are seenselflimited, but reactivation may occur.Treatment is generally reserved for active lesions that may impair vision, such as those in the fovea.combination of antimicrobials for the infection and corticosteroids to decrease inflammation.

Inactive scarActive scar with inflammationAdjacent to scar

RubellaSystemic involvement includes cardiac, hearing, and central nervous system abnormalities. Ocular findings include cataracts and glaucoma.Retinal manifestations include pigmentary changes that may mimic retinitis pigmentosa.The spotty areas of pigmentation are sometimes described as salt-and-pepper retinopathy

Lymphocytic Choriomeningitis VirusTransmitted by exposure to rodents. Systemic manifestations primarily involve the central nervous system, including hydrocephalus, microcephaly, calcifications, and developmental delay. Ocular manifestations consist of chorioretinal scars, primarily in the posterior retina. The appearance of these scars may be similar to those seen in toxoplasmosis and Aicardi syndrome.

ToxocariasisToxocara canis, a parasite - exposure to dog or cat feces or unclean food. Systemic involvement includes visceral larval migrans, usually in infants and toddlers. It may present with flulike symptoms. Ocular involvement - focal retinal granulomas, associated with inflammation and bands of traction tissue. Treatment is indicated if the vision is threatened.

Bacterial EndophthalmitisRare and potentially devastating infection of the vitreous and retina. commonly occurs as a result of penetrating ocular injury or as a complication of ophthalmic surgery. Rarely, endogenous endophthalmitis may develop in patients with endocarditis or other systemic disease. marked ocular inflammation with hypopyon.Prompt treatment with systemic and intravitreal antibiotics is usually necessary if vision is to be preserved.

INHERITED DISORDERS OFRETINAL FUNCTIONRetinitis PigmentosaCharacterized by dysfunction of the retinal photoreceptors (rods and cones).Patients with RP typically develop pigmentary changes in the retina, with clumps of hyperpigmented tissue that appear like bone spicules.

Leber Congenital AmaurosisA congenital form of RP - an autosomal recessive fashionIt presents within the first few months of life with poor or absent visual fixation and nystagmus. Poorly reactive pupils and marked farsightedness are usually present. The retina initially appears normal, but most patients develop pigmentary changes with age.

Systemic Disorders Associated with Retinitis PigmentosaBardet-Biedl syndrome is associated with developmental delay, extra digits on the hands and feet, obesity, and hypogonadism. Usher syndrome is associated with sensorineural hearing loss.

Stargardt Disease (Juvenile Macular Degeneration)Autosomal recessiveUnexplained vision loss, usually during the second decade. Caused by a mutation of the retina-specific ATP-binding transporter protein (ABCR). The retina often initially appears normal, and the child may be suspected of malingering.beaten metal appearance of the maculaSome patients have a characteristic dark appearance of the choroid on fluorescein angiography of the retina.

Neuronal Ceroid Lipofuscinosis (Batten Disease)Autosomal recessive - abnormal deposits develop in neuronal lysosomes.Present with decreased vision, developmental delay, and seizures.Ophthalmic findings include optic nerve atrophy and pigmentary deposits within the retina

Disorders Associated With Cherry-red SpotsTay-Sachs, Niemann-Pick,Sialidosis, andSandhoff disease.The appearance is due to accumulation of abnormal material in the ganglion cells surrounding the fovea

Other Inherited Disordersof Retinal FunctionBest vitelliform dystrophy. An autosomal dominant - mutation of the vitelliform macular dystrophy gene. Yellow cystic structure in the macula that may look like an egg yolk. The diagnosis is established by an abnormal electrooculogram, which reflects dysfunction of the retinal pigment epithelium.

Achromatopsia (rod monochromatism). Characterized by absent cone function.Infants present in a similar fashion to LCA, with minimal fixation and nystagmus in early infancy. Usually photophobic. Absence of cone responses - ERG

Congenital stationary night blindness. Less severe form of congenital RP.Infants typically present with nystagmus in the first few months of life, but visual function is not markedly impaired. Diagnosis - ERG

Juvenile retinoschisisAn X-linked disorder - inner layers of the retina separate. Initially fovea and Older develop peripheral retinal detachmentsProgressive vision loss. A characteristic ERG abnormality (a decreased scotopic b-wave with preserved a-wave) is diagnostic.

Joubert syndrome. maldevelopment of the cerebellar vermis, Imaging - molar tooth sign. It frequently presents with abnormal breathing in infancy. Other systemic features include hypotonia, ataxia, and developmental delay.Some patients with Joubert syndrome have a congenital form of retinal dystrophy that presents with poor visual responses and nystagmus in infancy.Ocular motor apraxia is a common feature.

RetinoblastomaMost common intraocular malignancy of infancy and childhood

Autosomal dominant inheritance

Affects 1:20,000 live births

Mean age of presentation is 18 months (unilateral at 24 months, bilateral at 13 months)

13q14 chromosome defect

Unilateral or bilateral (70% unilateral)

Genetics of RB

Clinical DescriptionLeukocoriaStrabismusRubeosisHypopyonHyphemaBuphthalmiaOrbital cellulitis

Clinical DiagnosisFundoscopyUltrasound imagingMagnetic resonance imagingComputed tomography

Ultrasound of RB

Grouping of Retinoblastoma

Group A

small tumors with round configuration.

tumors greater than 3 mm from fovea and greater than 1.5 mm from optic disc.

No intraocular tumor dissemination

Group BTumors still discrete but larger or closer to critical structures than group A.

Subretinal fluid extending no further than 5 mm from tumor base.

No intraocular tumor dissemination

Group CTumors that have progressed through group A and B.

Tumor dissemination located near the originating site.

Focal, fine, localized vitreous or subretinal seeding.

Group DMore extensive dissemination of intraocular tumor than in group C.SRF occupying more than one quadrant of retina.Upto total RD.Massive and / or diffuse vitreous seeding extending at distance from tumor

Group E

Tumors include any or all characteristics of group A through D.

Tumor features of effects associated with irreversible ocular morbidity

Choice of treatment depends on

Tumor sizeLocation LateralityPresence of vitreous or subretinal seedingPotential visual acuityTolerance of child for various therapiesRisk for second cancers

Current therapies for retinoblastomaEnucleationExternal beam radiotherapyBrachy therapyTranspupillary thermotherapyChemotherapy (local and systemic)Laser photocoagulationCryotherapyObservation (for spontaneously regressed tumors)

Regression patterns in RetinoblastomaType 0 regression with no tumor remnantType 1 regression with completely calcified remnantType 2 regression with noncalcified remnant

Regression patterns in RetinoblastomaType 4 - regression with flat chorioretinal scarType 3 regression with partially calcified tumor remnant

RETINAL HEMORRHAGEParturition-related HemorrhageMost common following vacuum-assisted delivery, occasionally following caesarean section. Vary from scattered posterior hemorrhages to diffuse bleeding in all quadrants of the eye. Usually resolve without sequela during the first few weeks of life.

Nonaccidental TraumaChild abuse,Often associated with intracranial hemorrhages and other signs of abuse. The hemorrhages may occur in any layer of the retina and vitreous hemorrhage may also occur.The presence of retinal hemorrhages is an important finding in the evaluation of patients suspected of abuse. Diffuse multilayered retinal hemorrhages, particularly in the absence of external signs of trauma, are highly suspicious for nonaccidental injury In severe cases of shaking injury the layers of the retina may split (retinoschisis). This produces a dome-shaped elevation overlying the macula, often with folds of retinal tissue bordering the lesion Blood layering may occur within this cavity, with the position of the blood dependent on how the patients head is positioned. This finding has been very rarely reported in infants with severe crush head injuries. In the absence of such a history and associated findings, retinoschisis cavities are essentially pathognomonic for nonaccidental injuries.

Retinoschisis with premacular folds

OTHER SYSTEMIC DISEASESASSOCIATED WITH SPECIFICRETINAL ABNORMALITIESTuberous Sclerosis (Bourneville disease)An autosomal dominant phakomatosis. Most cases represent new mutations. Systemic abnormalities include developmental delay, seizures, and tumors of the central nervous system, kidney, and heart. Characteristic skin lesions include ash-leaf spots, adenoma sebaceum, and subungual fibromas. Approximately one-third to one-half of patients with TS have retinal astrocytic hamartomas. In young patients these are typically smooth, elevated grayish nodules that are found in the posterior retina.

Adenoma sebaceumAsh-leaf spot

Tuberous sclerosis. Retinal astrocytic hamartomas(arrows), with appearance similar to retinoblastoma

Retinal astrocytic hamartoma with lobulated appearance, more commonly seen in older affected children.

Neurofi bromatosis Type 2Less common than neurofi bromatosis type 1 An autosomal dominant fashion. Patients uniformly develop acoustic neuromas.They do not have iris Lisch nodules. Posterior subcapsular cataracts may occur.A specific retinal abnormality associated with NF2 is an epiretinal membrane. These arise on the inner retinal surface and may cause a wrinkled appearance of the retina when they contract.Epiretinal membranes occur relatively commonly in adults, particularly the elderly.

Chronic Granulomatous DiseaseA disorder of phagocytosis - An X-linked fashion. Patients develop severe recurrent infections in multiple organ systems. Patients may develop idiopathic retinal pigment epithelial scarring along the course of the retinal blood vessels

Pigmentedperivascular lesions

Familial Adenomatous Polyposis (Gardner Syndrome)An autosomal dominant disorder in which affected individuals develop polyps in the colon with a high potential for malignant conversion. Congenital hypertrophy of the retinal pigmented epithelium is a fairly common retinal finding in normal individuals, characterized by circular areas of dark retinal pigmentation. Patients with Gardner syndrome develop similar lesions, but they are increased in number and have an ovoid appearanceThis retinal finding may be useful in identifying patients in families with Gardner syndrome who are at risk for the development of colon cancer.

areas of congenital hypertrophy of the retinal pigment epithelium

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