Retina and Vitreous

 

Macular Diseases:

 

Central Serous Retinopathy

Age-related Macular Degeneration (AMD)
Non-Neovascular, Neovascular

Non-neovascular AMD

Neovascular AMD

 

Ocular Histoplasmosis

 

Idiopathic CNV

 

Angioid Streaks

 

Pathologic Myopia

 

Epiretinal Membrane

 

Vitreomacular Traction Syndrome

 

Macular Hole

 

Valsalva Retinopathy

 

Purtscher’s Retinopathy

 

Terson’s Syndrome

Diabetic Retinopathy

 

Diabetic Retinopathy: Pathogenesis

 

Diabetic Retinopathy: Epidemiology

 

Diabetic Retinopathy:   Macular Edema

 

Grading Non-proliferative Diabetic Retinopathy (NPDR)

 

Proliferative Diabetic Retinopathy (PDR)

Systemic diseases effect on Diabetic Retinopathy

Metabolic Factors in Diabetic Retinopathy

Aldose reductase catalizes the conversion of glucose to sorbitol. This could be a theoretical cause damage to retina by causing an alteration in cellular metabolism and thickening of basement membranes.

Clinical Trials in Diabetic Retinopathy

 

Diabetic Retinopathy Study (DRS)

 

Early Treatment Diabetic Retinopathy Study (ETDRS)

 

Diabetic Retinopathy Vitrectomy Study (DRVS)

 

Sorbinil Retinopathy Trial

 

Diabetes Control and Complications Trial (DCCT)

 

Focal laser in clinically significant diabetic macular edema (CSDME)

Panretinal Photocoagulation for Proliferative Diabetic Retinopathy

Cataract Surgery in Diabetic retinopathy

 

Iris Neovascularization in Diabetes

 

Diabetic Examination Timetables

 

Vitrectomy in Diabetic Retinopathy

Retinal Vascular Disease

 

Systemic Hypertension

 

Sickle Cell Retinopathy

Differential Diagnosis of Peripherial Retinal Neovascularization

Retinopathy of Prematurity (ROP)

Retinopathy of Prematurity- Epidemiology

ROP- Pathogenesis

ROP- Location

ROP- Extent

ROP- Staging (Severity)

ROP- Screening

ROP- Treatment

  • O2 identified as factor in 1950's, curtailing use of oxygen ended epidemic of infant blindness (but increased mortality from RDS)
  • Cryotherapy of avascular retina in threshold disease reduces cicatirix and retinal detachment from 47% to 25% at 1 year.
  • 5% of patients undergoing cryotherapy develop cardiopulmary arrest (consult peds prior)
  • most now use scatter PRP of avascular retina which is felt to be less traumatic, equal if not better outcomes.
  • Scleral buckle or vitrectomy in stage 4 or 5: 30% initial reattachment rate, but only 10% of these have ambulatory vision long term.

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    Branch Retinal Vein Occlusion (BRVO)

     

    Central Retinal Vein Occlusion (CRVO)

     

    Nerve Fiber Layer Infarction (NFL) a.k.a. cotton wool spot

     

    Branch Retinal Artery Occlusion (BRAO)

     

    Central Retinal Artery Occlusion (CRAO)

    Ocular Ischemic Syndrome (OIS)

  • Ocular Symptoms occur after >90% carotid artery obstruction
  • aching pain, slow decrease in vision over weeks, slow recovery after bright light
  • age >50, unilateral 80%
    •
  • Signs:
  • Iris neovasculariztion (66%)
  • Decreased IOP 2° to ciliary body ischemia
  • Anterior chamber cell (20%)narrow ret arteries
  • Dilated retinal veins (not tortuous), hemorrhage, microaneurysms, disc and retinal neovasculariztion
  • FFA delayed choroidal filling (60%), delayed AV transit (85%)
  • ERG decreased a and b waves (outer and inner retinal ischemia).
    •
  • 50% also have coronoary artery disease,
  • 25% stroke, 20% perepherial vascular disease requiring surgery
  • 5-year mortality 40% (coronoary artery disease)
  • If iris neovascularization present, 90% decrease vision to <20/200 by 1 year (PRP effective in 35%)
  • Treatment: Carotid endarterectomy if >70% occlusion.
  • Decreases risk of stroke to 9% vs 26%
  • Watch for increased  IOP after surgery (ciliary body reperfusion)
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    •  

    Vasculitis

    Eales Disease

    Cystoid Macular Edema (CME)

  • Honeycomb-like intraretinal spaces
  • Flourscein angiography shows: early multiple small focal leaks of the perifoveal capillaries, late pooling in cystoid spaces leads to the flower petal pattern (pooling in Henle's layer)
  • Severe cases can have vitreous cell and optic nerve head edema
  • Etiology: Diabetic Retinopathy, CRVO, BRVO, uveitis, Retinitis Pigmentosa, Intraocular surgery, CNVM all result in abnormal permeablility of retinal capillaries
  • Rare causes: juvenile retinoschesis, Goldmann-Favre, nicotinic acid
  • Irvine-Gass syndrome:
  • Post Cataract surgery 60% post ICCE, less common with posterior capsule intact
  • Peak incidence 6-10 weeks post-op.
  • Spontaneous resolution 95% usually within 6 months.
  • Usually worse with vitreous loss, inflammation, iris prolapse.
    •
  • More severe or chronic CME can lead to permanent visual loss
  • More commonly associated with hypertension, diabetes, age >60, uveitis
  • Treatment:
  • Effect of any treatment is difficult to evaluate given 95% rate of spontaneous resolution
  • Most use topical, periocular and/or systemic corticosteroids, NSAIDS/ prostaglandin inhibitors, Carbonic anhydrase inhibitors.
    •
  • Prophylaxis: topical and systemic Indocin has been shown to be effective.
  • If any vitreous adhesions to the iris or corneal wounds, Nd:Yag laser vitreolysis or automated vitrectomy may be helpful.

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    Coat's Disease

  • Multiple vascular anomalies: telangectasias, venous dilation, microaneurysms, fusiform capillary dilation
  • lipid deposition, hard exudates in macula
  • Associated with exudative retinal detachments and capillary nonperfusion (although neovascularization is rare)
  • Occasionaly a macular disciform scar is the presenting lesion
  • Abnomal vessels are incompetent and lead to retinal or subretinal accumulation of serum and blood products
  • Not hereditary and no systemic vascular abnormalities
  • More common in males 85%
  • Gradually progressive, worse if age <4
  • Treatment: laser or cryotherapy will halt progression, multiple retreatments might be required,
  • Severe cases might require retinal reattachment surgery
    •
  • Differential diagnosis:
  • Familial exudative vitreoretinopathy
  • facioscapulohumeral muscular distrophy
  • retinopathy of prematurity
  • branch retinal vein occlusion
  • juxtafoveal retinal telangiectasis
  • radiation retinopathy
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    •  

    Juxtafoveal Retinal Telangiectasis

  • Capillary incompitence and exudation leading to decrease vision
  • Group 1:
  • unilateral parafoveal telangiectasis, more common in males
  • Congenital or acquired
  • Appears as a variant of Coats disease with a Circinate type exudate,
  • Treatment:  laser photocoagulation
    •
  • Group 2:
  • bilateral parafoveal retinal thickenin more thick temporally,
  • RPE hyperplasia often present with subsequent CNVM
  • Vision loss ranges from mild to severe
  • 33% have abnormal glucose tolerance
  • Does not respond to laser treatment
    •
  • Group 3:
  • Bilateral progressive perifoveal obliteration of the capillaries
  • Does not respond to laser treatment
    •
  • Ddx: BRVO, diabetic retinopathy, radiation retinopathy, carotid artery occlusive disease

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    Retinal Arterial Macroaneurysm (RAMA)

  • Acquired retinal vascular abnormalities
  • Hypertension associated in 2/3rds
  • Bilateral in 10%, often multiple lesions
  • Hemorrhages are sub-internal limiting membrane, intraretinal and subretinal, vitreous hemorrhage also possible
  • Sclerosis and spontaneous closure often occur
  • Retinal edema may occur. Laser photocoagulation if it threatens macula.
  • Laser can cause distal vascular thrombosis

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    Retinal AVM's (Racemose)

  • Unilateral and not inherited
  • No leakage on FFA
  • Ipsilateral artero-venous malformation of face, orbit, or brain is Wyburn-Mason
    •

    Wyburn-Mason syndrome

     

    Cavernous Hemangiomas

  • Grapelike cluster of vessels that fill slowly on FFA
  • No leakage or SRF
  • Usually no symptoms or treatment necessary
  • Most are sporadic
  • Some autosomal dominant and associated with skin and CNS lesions.
  • A syndrome of disseminated cavernous hemangiomatosis results in death in infancy
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    Choroidal Hemangioma

  • Acquired
  • Isolated mass causing exudative fluid production and secondary macular dysfunction
  • Red-orange, distinct border, transilluminates
  • Can be confused with amelanotic choroidal melanoma
  • Usually in the posterior pole
  • Overlying cystic retinal changes or neurosensory retinal detachment
  • FFA: large choroidal vessels visible unless interference from RPE changes
  • Ultrasound: high internal reflectivity
  • Treatment: photocoagulation may be beneficial to decrease exudation
    •
  • Congenital
  • Diffuse hemangioma: "Tomato catsup fundus"
  • Associated with Sturge-weber syndrome
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    •  

    Choroidal Ischemia

  • Result of atherosclerosis, malignant hypertension or embolism.
  • Symptoms depend on degree and location of ischemia. Eg. underling optic nerve or macula
  • Permanent sequellae: Elshnig spots and Siegrist streaks

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    Uveal Effusion Syndrome

  • Abnormal uveoscleral outflow 2º to nanophthalmos, scleritis, idiopathic uveal effusion, or other states that cause abnormal scleral composition or thickness
  • Ocular findings:
  • Vision fluctuation
  • hyperopia common
  • glaucoma common
  • Exudative retinal detachment
  • Ciliochoroidal detachment
  • Abnormal episcleral vessels
    •

    • Congenital and Hereditary Diseases

     

    Diffuse Retinal Dystrophies

     

    Congenital color deficiency

     

    Goldman-Favre (Enhanced S-Cone syndrome)

     

    Congenital Stationary Night Blindness (CSNB)

     

    Nictalopia with Abnormal Fundus

     

    Fundus Albipunctatus

     

    Ogushi Dz

     

    Retinitis Pigmentosa (Rod-Cone Dystrophy)

     

    Leber congenital amaurosis (LCA): Autosomal Recessive

     

    Cone-Rod Dystrophies

  • Not as well studied as Retinitis Pigmentosa (Rod-Cone)
  • Central Va loss and poor color Va., photophobia
  • Often Bull's eye fundus with accumulation of yellow material in RPE
  • Loss of cone function on ERG (photopic)
  • Difficult prognosis: because some benign and others legally blind in childhood
  • Difficult to manage: education, Low Vision, refraction, amsler, communication with teachers

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    Macular Dystrophies

     

    Stargardt's Disease (Fundus Flavimaculatus)

  • Signs:
  • Pisciform flecks: discreet yellow drumsticks in RPE
  • May have bull's eye macular appearance
  • Only posterior pole involved is called Stargardt's disease
  • Flecks throughout fundus is called fundus flavimaculatus
  • Lots of flecks outside the macula is a poor prognostic sign
    •
  • May progress to nonspecific atrophy of macula with a beaten bronze appearance
  • Vision usually 20/50 - 20/200
  • Presentation: 33% 1st decade of life, 33% 2nd decade and 33% other
    •
  • Genetics:
  • ABCA4 gene (ATP Binding Cassette): catalyzes movement of visual cycle
  • 40% have mutation
    •
  • Ddx: Cone dystrophy, ceroid lipofuscinosis, pattern dystrophy
  • ERG helps determine prognosis and helps make diagnosis but is not specific. Any ERG finding possible but the poorer the ERG the worse the prognosis
  • Get FFA to look for "dark choroid" phenomonon
  • bright ret vessels on black background. Absence of FFA changes does not rule out the disease.
    •
  • Autoflourescent areas with peripapillary sparing on ICG photography
  • Low vision referral helpful.

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    Best Disease (vitelliform dystrophy)

  • Signs:
  • Yolk-like (vitelliform) yellow macular lesion which breaks down and scars like geographic atrophy
  • Classic stages are really different phenotypes
  • Rarely onset in adult life, usually starts in childhood or young adulthood
  • Vision often preserved in at least one eye well into adulthood
  • late stages have nonspecific atrophy making the diagnosis difficult
  • Occasional choroidal neovascularization
  • ERG usually normal;
  • EOG Abnormal (Arden ratio<1:1.5, often <1:1.1 (dark:light))
  • EOG always abnormal and can be a marker of carriers
  • EOG is recorded in millivolts and represents changes in RPE electrical potential
  • Healthy RPE potential changes 2 fold in light
  • Genetic test much easier to do
    •
  • Autosomal Dominant, variable expression
  • Bestrophin gene mutation on Chromosome 11
  • All 36 mutations are in the same coding region
  • 25% don't have a family history
    •
  • Lipofuscin-like deposits in RPE and sub-RPE
  • Ddx: vitelliform lesions in adults and normal EOG (or negative genetic testing for bestrophin mutation):
  • foveomacular dystrophy (similar course to pattern dystrophy) appears in adults without dominant family history
  • coalescence of drusen
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    Malattia Leventinese (diffuse drusen, dominant drusen, Doyne's honeycomb dystrophy, guttate choroiditis)

  • Age <50, drusen extends outside arcades, usually in nasal retina
  • No known inheritance pattern (not Autosomal Dominant)
  • Cuticular drusen / basal laminar drusen - myriad tiny dots
  • Va good if lesions outside fovea and are discrete
  • Lesions may coalesce to vitelliform macular lesions although vision can remain good unless RPE atrophies
  • Mechanism of drusen formation is unknown but might be related in defects in basement membrane function. Some hereditary retinal disorders that affect basement membranes such as Alport syndrome and membranoproliferative glomerulonephritis type II have drusen-like deposits

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    Pattern Dystrophy

  • A group of diseases
  • Good vision under age 50
  • Granular or reticular RPE pigmentation and no drusen
  • Sjogren reticular dystrophy:
  • Autosomal Recessive
  • Network of pigmented lines in the macula extending to the perephery
    •
  • Butterfly dystrophy:
  • Autosomal Dominant
  • Pigment radiates from fovea in a pattern resembling a butterfly's wings
    •
  • Usually present with mild decreased vision or metamorphopsia
  • Normal functional and ERG testing except for a borderline or mildly reduced EOG
  • Prognosis usually good except risk of geographic atrophy age >60 causing decreased vision
  • Associated with ABCA4, peripherin/RDS mutations (different mutations in the same gene cause Retinitis Pigmentosa)

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    Sorsby Macular Dystrophy

  • Autosomal Dominant,
  • Bilateral subfoveal choroidal neovascularization around age 40.
  • Nictalopia, ERG mimics vitamin A deficiency
  • Early numerous fine drusen or confluent plaque
  • MMP inhibatory gene: matrix metalloproteinase

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    North Carolina Dystrophy

     

    Choroidal / Peripheral Dystrophies

     

    Choroideremia

  • X-Linked, Xp21.2 mutation in the cell membrane anchor component of a Rab geranylgeranyl transferase protein
  • Late stage total absence of choroid, choriocapillaris, and RPE
  • Nictalopia age <20
  • Va <20/200 by age 50.
  • Early pigment mottling near the equator leads to atrophic areas that spread
  • ERG abnormal early, absent late
  • Female carriers have mottled fundus and no symptoms
  • Ddx: Gyrate atrophy, Retinitis Pigmentosa

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    Gyrate Atrophy

  • Autosomal Recessive, mutation in enzyme ornithine aminotransferase
  • Nictalopia age <10, progressive visual field loss
  • Va <20/200 by age 40.
  • Fundus: large peripherial areas of atrophy, coalesce to a scalloped border
  • Pathogenesis relates to decreased serum ornithine
  • Dietary restriction of arginine very difficult
  • Vitamin B6 supplimentation works in some

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    X-linked juvenile retinoschisis

  • A diffuse retinal disease
  • All cases have some degree of  foveal schisis which appears as subtle cysts with starlike radiating fine folds
  • No leaks on FFA from fovea
  • Vision is only mildly reduced
  • Peripherial splitting in severe cases of the NFL (senile retinoschesis has split in outer plexiform layer)
  • Primary defect is in the mueller cells
  • May develop Retinal detachment or vitreous hemorrhage
  • ERG loss of b-wave (diffuse split of inner and outer retina)

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    Systemic Diseases affecting the Retina

     

    Multi-system diseases with Retinal Involvement

     

    Infantile syndromes

  • See: Syndromes page
  • Aicardi syndrome
  • Joubert syndrome
  • Neuronal ceroid lipofuscinosis
  • Alstrom syndrome
  • Zellweger syndrome
  • Ophthalmic manifestations overlap with Leber's congenital amaurosis, which has NO systemic associations
    •
  • Any infant with abnormal ERG should be screened for congenital syndromes and metabolic disease before a diagnosis of leber's is made

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    Bardet-Biedl

  • Autosomal Recessive, chromosome 16, mulitsystem involvement
  • Obesity, polydactyly, hypogonadism, mental retardation
  • Pigmentary retinopathy: macular mottling, peripherial atrophy, no bony spicules.
  • ERG nonrecordable
  • Laurence-Moon syndrome: spastic paresis, choroidal atrophy, no obesity, no polydactyly
  • Alstrom syndrome: add Diabetes mellitus and deafness

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    Usher's syndrome

  • Most common cause of combined deafness/blindness in US
  • Autosomal Recessive, heterogeneous group
  • Myosin gene (axonemes in cilia, photoreceptors)
  • Type I: profound sensorineural hearing loss, unintelligible speech, absent vestibular fxn.
  • Progressive Retinitis Pigmentosa in teens, severe visual impairment
  • ERG nonrecordable
    •
  • Type II: mod sensorineural hearing loss, normal vestib fxn.
  • Retinitis Pigmentosa onset age 20, reasonable vision into adulthood
  • ERG attenuated but recordable.
    •
  • Best distinction between type I and II early on is vestibular function (have patient walk a line)
  • Ddx: Alstrom, Leber congential amaurosis, Bardet-Biedl, retinal-renal, Refsum, mitochondrial myopathies, congenital  rubella, mucopolysaccharidoses

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    Neuromuscular Disorders

  • Spinocerebellar degenerations (Friedreich's ataxia): pigmentary retinal degeneration
  • Olivopontocerebellar atrophies:
  • Autosomal Dominant or mitochondrial
  • developmental delay, ataxia, poor vision
  • diminished ERG.
  • Infants or adults can be affected
    •
  • Myotonic dystrophy:
  • fundus similar to pattern dystrophy
  • variable expression
  • little visual significance
  • hypotony
    •
  • Duchenne muscular dystrophy:
  • usually no visual symptoms, but striking negative waveform on ERG (like CSNB)
    •
  • Kearn-Sayre syndrome (mitochondrial):
  • progressive externernal ophthalmoplegia: see: CPEO
  • pigmentary retinopathy
  • cardiac conduction abnormalities
  • if full blown systemic KS, may have nonrecordable ERG.
    •
  • NARP syndrome (mitochondrial myopathy): Neurogenic weakness, Ataxia, Retinitis Pigmentosa.

    •  

    Retinal-Renal Dysplasia

  • aka Juvenile nephronophthisis
  • Autosomal Recessive, juvenile onset renal failure, sectoral pigmentary degeneration
  • Others: Alport, MPGN II, Alstrom, Bardet-Biedl

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    Other Organ system diseases with Retinal involvement

  • GI:
  • Gardner syndrome (familial adenomatous polyposis): CHRPE lesions (small multiple, bilateral)
    •
  • Dermatologic:
  • Ichthyosis: Refsum and Sjogren-Larsson;
  • Incontinentia pigmenti:
  • females, brown whorls on trunk
  • retinal pigmentary changes
    •
  • Pseudoxanthoma elasticum associated with angioid streaks, peau d'orange fundus
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    Cancer-Associated retinopathy

  • paraneoplastic/immunologic
  • any cancer can be associated but often lung or breast
  • rapid onset of vision and visual field loss
  • fundus appearance: arterial narrowing, no pigmentary changes
  • ERG is severely reduced
  • high serum titer of recoverin (an enzyme in visual pathway)
  • any late onset rapidly progressive visual loss should raise suspicion of an occult malignancy

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    Metabolic/CNS Defects with retinal involvement

     

    Albinism

     

    Albinism- General Characteristics

  • See syndrome description in syndrome index
  • A group of inherited conditions involving the melanin system of the eye and/or skin
  • Most common forms: oculocutaneous albinism (tyrosinase + and -) and X-linked ocular albinism
  • congenitally decreased vision, nystagmus, iris transillumination defects, hypopigmented fundus especially perepherial to the posterior pole
  • true albinism has hypoplastic fovea, no foveal reflex, no foveal pit on histopathology
  • abnormal retinogeniculostriate projections (temporal fibers decussate rather than going to ipsilateral Lateral Geniculate Nucleus) leads to strabismus and precludes stereopsis. Seen with asymmetric visually evoked cortical potentials
  • Vision ranges from 20/40 to 20/200
  • Nystagmus can begin as early as 2-3 months of life
  • Direct correlation between degree of hypopigmentation and visual acuity
    •
  • Hair bulb test: rarely used today
  • Most are tyrosinase positive, not very helpful
  • Molecular genetic testing is becoming more available and better to determine type by testing mutations in the TYR and P genes
  • Sensioneural deafness reported with both Oculocutaneous and Ocular types
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    Ocular Albinism: only eyes involvoed

  • X-linked
  • decreased number of melanosomes or macromelanosomes present on skin biopsy
  • Female carriers have patchy fundus hypopigmentation ("mud-splattered") from lyonization
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    Oculocutaneous albinism: eyes and skin,

  • Autosomal Recessive
  • OCA1A: Two TYR gene mutations (11q14-q21) causing no tyrosinase to be produced; no melanin
  • OCA1B: Two TYR gene mutations causing at least one copy of a partially active tyrosinase enzyme: less melanin
  • OCA2: P gene mutation (15q11-q13) hair pigmented but not skin, some iris pigment
  • Near the region associated with Prader-Willi and Angelman syndromes (1% association between OCA2 and those two syndromes)
    •
  • OCA3: TYRP1 gene mutation (9q23) described in those of african descent
  • OCA4: MAPT gene mutation (5p) one human case
  • decreased amount of 1º melanin in each melanosome, tyrosinase (melanin synthesis)
    •

     

    Two lethal subtypes of Oculocutaneous Albinism:

  • Chediak-Higashi:
  • Autosomal recessive, chromosome 1
  • Decreased immune function, often bone marrow transplant is needed
  • Giant peroxidase-positive lysosomal granules in granulocytes
  • Hypopigmentation is variable
  • Die at a younger age than the following suptype
    •
  • Hermansky-Pudlak
  • Autosomal recessive, 4 different mutations described (HPS1-4)
  • Puerto-Rican and Swiss families
  • Extremely variable phenotype (severe OCA to normally pigmentation)
  • Easy brusing/variable bleeding diathesis: deficency of storage granules in platelets
  • ceroid storage disease affecting the lung and gut primarily
  • Death occurs from intersitial lung disease or colitis, rarely from hemorrhage
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    •

    Albinism- Diagnosis:

  • Identify classic characteristics
  • Multichannel flash VEP can demonstrate asymmetric decussations
  • Molecular analysis of the TYR and P genes if available
  • For Ocular albinism: Examine mother of affected males, skin biopsy can confirm diagnosis if macromelanosomes found.  Macromelanosomes is not specific for OA. (seen in Chediak-Higashi, Hermansky-Pudlak, neurofibromatosis, xeroderma pigmentosum, nevus spillus and others)
  • Look for associated findings: brusing, bleeding, infections, hearing problems
    •

     

    Albinism-Treatment:

  • Correct refractive error
  • Tinted lenses: Corning 511 or 527 may reduce photophobia
  • Low vision aids
  • Strabismus surgery
  • Avoid sun exposure (high rate of squamous and basal cell carcinomas), sunscreen in excess of 32 spf in addition to long sleeves and hat
  • Group support: National Orginization for Albinism and Hypopigmentation (NOAH)
    •

     

    Albinoidism:

     

    Neuronal ceroid lipofuscinosis (NCL)

     

    Peroxisomal Disorders

  • Autosomal Recessive, defective oxidation, accumulation of long chain fatty acids
  • Zellweger syndrome:
  • infantile retinal degeneration, hypotonia, psychomotor retardation, seizures, characteristic facies, renal cysts, hepatic interstitial fibrosis. Death in infancy
    •
  • Adrenoleukodystrophy (ALD): similar to Zellweger syndrome but live to age 7-10
    •

     

    Refsum disease

     

    Mucopolysaccharidoses (MPS)

  • defects in catabolic lysosomal exoenzymes
  • precursors accumulate: mucopolysaccharides, keratan/dermatan/heparan sulfate
  • only heparan sulfate causes eye disease
  • MPS I-H (Hurler's), and MPS I-S (Scheie): Autosomal Recessive, coarse facies, mental retardation, corneal clouding, retinal degeneration, abnormal ERG
  • MPS II (Hunter): X-Linked, same as MPS I but dwarfed, no corneal clouding
  • MPS III (Sanfilipino): milder somatic disease but severe pigmentary retinopathy

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    Other Storage Diseases

  • Tay-Sachs (GM2 gangliosidosis type I): most common, deficent subunit A of hexosaminidase A. Glycolipid accumulation in brain and retina. Death by age 2-5. Cherry red spot.
  • Gaucher: no cerebral involvement. Accumulation of glucosylceramide in liver, spleen, and skin, Gaucher cells in marrow. Some with cherry red spot others have white subretinal midperepherial fundus lesions
  • Niemann-Pick: lack of different sphingomyelinase isoenzymes.
  • Type A (acute): cherry red spot 50%
  • Type B (chronic): milder, no CNS involvement, pathologic macular halo (also called sea-blue histiocyte syndrome)
    •
  • Fabry's: X-linked, ceramide trihexoside accumulation in smooth muscle of vessels and kidneys, skin, GI, CNS, heart and reticuloendothelial system. Burning paresthesias. Corneal whorls (verticillata), tortuous conjunctival vessels, dilated & tortuous retinal vessels, lens changes.
  • Cherry Red spot also seen in sialidoses and galactosialidoses: Sandhoff (GM2 gangliosidosis type II), Generalized gangliosidosis (GM1 type I), Goldberg Cotlier (GM1 type IV), sialidoses, galactosialidoses, muclipidosis I, cherry-red spot-myoclonus syndrome.
  • Mucolidiosis IV: causes a diffuse retinal degeneration

    •  

    Cystinosis

  • Autosomal Recessive, intralysosomal cystine accumulation,
  • Three types: nephropathic, late-onset, benign
  • All have accumulation in the cornea, only nephropathic type has retinopathy
  • Onset age 8-15 mo: chronic renal failure, growth retardation, renal rickets, hypothyroid.
  • Retinopathy: patchy depigmentation of RPE alternating with randomly distrubuted pigment clumps
  • No significant visual disturbance
  • Treatment with cysteamine allows cystine to leave lysosome

    •  

    Systemic Drug Toxicity

     

    Chloroquine derivatives

  • Used to treat collagen vascular diseases and as malaria prophylaxis
  • Symptoms of toxicity: blurred vision. color vision loss, difficulty with dark adaptation
  • Fundus: Bull's eye macular depigmentation and atrophy
  • Paracentral scotomas, corneal verticillata
  • Rare if total dose <300 g or daily dose <250 mg
  • Hydroxychloroquine is safer (400 mg QD)
  • Early detection is key but no accepted standard: have baseline exam upon initiating treatment, with photos, color vision, visual fields (10-2 white target)
  • Follow-up Q 6-12 mo.
  • Consider discontinuing drug at first sign of toxicity, however symptoms may progress despite stopping

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    Phenothiazines

  • Concentrated in uveal tissue and RPE
  • Chlorpromazine (Thorazine):abnormal pigmentation of eyelids, conjunctiva, cornea, posterior and anterior subcapsular cataracts. Retinopathy rare
  • Thioridazine (Mellaril): severe retinopathy can develop in a few weeks or months. Rare at <800 mg/day.
  • Fundus: coarse PRE stippling progresses to widespread patchy atrophy.
  • Late in the disease the fundus looks like choroideremia, with nictalopia and visual field loss
    •

     

    Tamoxifen

     

    Canthaxanthine

     

    Methoxyfluorane

     

    Accutane (isotretinoin)

     

    Digitalis

     

    Viagra (sienafil)

     

    Retinal Detachment / Retinal breaks

     

    Retinal Breaks- definitions

     

    Posterior Vitreous Detachment (PVD)

     

    Traumatic Retinal Breaks

     

    Lesions that predispose to Retinal Detachment

     

    Lesions that do not predispose to Retinal Detachment

     

    Retinal Detachment Prophylaxis

     

    Rhegmatogenous Retinal Detachment (RRD)

    Tractional RD

  • Vitreous membrane 2º to penetrating injury or proliferative retinopathy (e.g. Diabetic retinopathy)
  • Usually smooth and immobile membrane visulaized with a contact lens
  • Concave anteriorly and rarely extends to ora
  • Membrane can cause 2º rhegematous retinal detachment if retina tears
  • Treatment: pars plana vitrectomy to release traction

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    Exudative RD

  • Critical to recognize because treatment is not surgical
  • Damage to vessels and RPE cause fluid accumulation in the subretinal space
  • Neoplasm and inflammation are leading causes
  • Shifting fluid is highly suggestive

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    Retinoschisis (senile)

  • 50%-80% bilateral, inferotemporal, and associate with hyperopia
  • Typical peripheral cystoid degeneration: present in nearly all adults from ora to 3 mm posterior, bubbly retinal appearance. This lesion progresses to senile retinoschisis
  • Split in outer plexiform layer
  • Schisis is smooth domed, no tobacco dust, absolute scotoma, no shifting fluid as apposed to true retinal detachment
  • Not to be confused with X-linked juvenile retinoschisis

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    Reticular peripheral cystoid degeneration:

     

    Vitreous Diseases

     

    Tunica Vasculosa Lentis

  • Mittendorf's dot - remnant of hyaloid system, small white round inferonasal on posterior lens
  • Bergmeister's papilla - posterior remnant at margin of optic nerve head
  • Prepapillary Vascular Loops - normal vessels that grow into Bergmeister's papilla, usuually <5mm high. 95% arterial, 5% venous.  Can rarely have BRAO, amaurosis fugax, or vitreous hemorrhage as a result of this malformation
  • Entire hyaloid artery may persist
  • These abnormalities are not usually visually significant

    •  

    Persistant Hyperplastic Primary Vitreous (PHPV)

  • 90% unilateral, In the differential of  leukocoria
  • Not only does the hyloid system fail to regress, it undergoes hyperplasia
  • Unilateral, associated with microphthalmos and secondary pupillary block
  • Anterior PHPV
  • Hyaloid artery remains, white fibrovascular membrane behind lens
  • Retrolental plaque may contain fibrous tissue, adipose, smooth muscle or cartilage and may put traction on zonules
  • Associated with microphthalmos, shallow anterior chamber, POAG, and dehiscence of posteror capsule with lens swelling, cataract, acute angle closure glaucoma
  • Poor visual outcome is common even with surgery to remove membrane
    •
  • Posterior PHPV
  • stalk of tissue at optic nerve, fans out anterior to the retina
  • microphthalmos, normal AC and lens
    •
  • Progressive posterior cataract and elongated ciliary processes
  • can be associated with anterior PHPV or isolated
    •
  • Ddx: ROP, toxocara, familial exudative vitreoretinopathy, medulloepithelioma (very rare)

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    Optically Empty Vitreous

  • Vitreous liquefaction with thin cortical layer at lens
  • Associated with lattice and abnormal ERG
  • Ocular syndromes: Jansen's (risk of RD), Wagner's (no RD), both autosomal dominant, myopia, cararact, strabismus
  • Systemic syndromes: dwarfism, marfanoid, Stickler, Weill-Marchesani

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    Stickler's Syndrome

     

    Familial Exudative Vitreoretinopathy (FEVR)

     

    Asteroid Hyalosis

  • Multiple white opacities that consist of calcium phospholipids
  • Associated with Diabetes
  • Overall incidence 1:200
  • Average Age 50
  • Unilateral in 75%
  • Usually normal vision

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    Cholesterolosis

  • Multiple yellowish white, gold, multicolored cholesterol crystals
  • In vitreous and anterior chamber
  • Only seen in eyes that have had repeated and severe trauma or surgery with vitreous hemorrhage
  • Synchysis scintillans - crystals are highly refractive
  • Usually with posterior vitreous detachment, crystals settle inferiorly

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    Amyloidosis

  • Bilateral vitreous opacities, Autosomal Dominant or isolated
  • Retina: hemorrhage, exudates, cotton-wool spots, neovascularization
  • Can deposit in: orbital tissues, muscles, eyelids, conjunctiva, cornea, iris
  • Systemic deposition: polyneuropathy, CNS, heart, skin, GI, etc.
  • Extracellular vitreous opacities appear adjacent to retinal vessels starting posteriorly then progressing anteriorly
  • The early deposits appear like granular whispy fringes that enlarge
  • The vitreous looks like glass wool late
  • Can appear similar to chronic vitreous hemorrhage

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    Vitreous Hemorrhage

  • Causes:
  • Diabetic retinopathy 50%,
  • Retinal break 15%
  • PVD 10%
  • Rhegmatogenous retinal detachment 5%
  • Neovascularization from a retinal vascular occlusion 5%
  • Blunt trauma: damage to vessels, ciliary body, retina, choroid
    •
  • Other rare causes: congenital retinoschisis, pars planitis, trauma (child abuse)
  • Echography if no view
  • Can prescribe 2 days bed rest with head of bed elevated and reexamine if echo not available

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    Trauma of the Posterior Segment

     

    Evaluation

  • History: Time and mechanism, work related, early treatment (antibiotics, tetanus), other injuries, last oral intake, eye status prior, risk of intraocular foreign body, wearing glasses, force of injury
  • Examination: if open globe keep exam to minimum.  Vision and RAPD could give prognostic information
  • Sympathetic Ophthalmia
  • Consider enucleation if no hope of visual recovery
  • Always initially close the wound and retain the eye if at all possible
  • Explore with vitrectomy approach to determine anatomic potential
  • Enucleate within 2 weeks to reduce risk of sympathetic ophthalmia
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    Blunt Trauma

     

    Commotio Retinae

  • Damage to outer retinal layers by shock wave
  • Retinal whitening hours after, usually posterior pole (Berlin's edema)
  • Mechanism unknown: cellular edema, glial sewelling, photoreceptor damage
  • Vision may decrease to 20/200, but good prognosis for recovery
  • Clears in 3-4 weeks
  • No specific treatment necessary
    •

     

    Choroidal Rupture

  • Choroid compressed in anterior-posterior axis and stretched in horizontal axis
  • Bruch's membrane and RPE are inelastic and can cause tear in choriocapillaris that is seen as subretinal hemorrhage
  • May be multiple and concentric to the optic disc, if they extend through the macula, permanent vision loss possible
  • No immediate treatment
  • Rarely choroidal neovascularization may occur as a late complicton
  • Rollow amsler grid if rupture is near the macula
  • Usually choroidal neovascularization near the macula is not as severe as that with age-related macular degeneration. Laser treatment may not be necessary in these cases
    •

     

    Scleral Rupture

  • Ruptures at weak points:  limbus or posteror to the muscle insertions
  • Signs: decreased ductions, chemosis, hemorrhage, deepened anteroir chamber, severe vitreous hemorrhage, decreased intraocular pressure
  • Rule out intraocular foreign body in all cases

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    Penetrating Injury

  • Prognosis is related to location and extent of injury and associated damage
  • Must explore posterior extent of any laceration if possible
  • 360º peritomy may be helpful if suspected posterior rupture
  • Meticulous closure with reposited or excised uvea
  • Commonly for corneal repair 10-0 nylon is used, for sclera 7-0 or 6-0 non-absorbable suture
  • Small posterior wounds that cannot be reached can be allowed to heal spontaneously 2º to risk of vitreous extrusion with manipulation
  • Late complications: tractional retinal detachment, cyclitic membrane, phthisis bulbi
  • To avoid late complications: remove vitreous scaffold to prevent fibrous proliferation
  • the timing debated, usually 4-14 days is enough time to allow spontaneous posterior vitreous detachment and decrease risk of hemorrhage in an inflamed eye
    •

    •  

    Perforating Injury

  • By definition there is an entrance and exit wound
  • Fibrous proliferation grows on vitreous scaffold between the two wounds
  • By day 7, wounds close by fibrosis
  • Consider vitrectomy after day seven to prevent late complications: tractional retinal detachment, cyclitic membrane and phthisis bulbi.

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    Intraocular Foreign Body

  • Suspect in any metal on metal (hammering, machinery, etc.)
  • CT scan to locate (MRI contraindicated if metallic)
  • Ultrasound if nonradiopaque
  • Pars Plana Vitrectomy
  • Pars Plana magnetic extraction if small, easily seen
  • Rorceps removal if large, opaque media
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  • Materials
  • Inert: stone, sand, glass, porcelain, plastic, platinum, silver, gold, procelain
  • Copper: chalcosis, esp. toxic, acute with severe inflam
  • prompt removal required or loss of eye
  • if >85% copper, non-infectious suppurative endophthalmitis
  • poorly responsive to steroids
  • prompt removal allows cure
    •
  • if <85%, Chronic Chalcosis: copper alloy (brass, bronze) - basement membrane deposits
  • deposits in membranes, greenish aqueous and iris particles, sunflower cataract, copper on Decemet's membrane (Kayser-Fleisher ring), retinal degeneration
    •
  • Iron (Steel): siderosis, deposits in epithelial and neuroepithelial tissues (iris, lens, ciliary body and RPE)
  • Infection uncommon
  • Damage depends upon amount of oxidation, amount of Fe++(ferrous) oxidizing to Fe+++(ferric)
  • Haber-Weiss reaction: hydroxyl radicals and peroxide
  • Cell membrane damage, especially photoreceptors leading to nictalopia, reduced visual fields and blindness
  • Rust colored corneal ring, iris heterochromia, mydriasis, cataract, brown trabecular meshwork vitreous opacity, glaucoma, retinal pigmentation and degeneration
    •
  • Mercury, aluminum, nickle, zinc, lead- variable amounts of inflammation
  • Vegetable matter- higher chance of infection, severe granulomatous reaction
    •

    •  

    Post-traumatic Endophthalmitis

  • Appears in approximately 5% of penetrating injuries, higher with IOFB
  • Progresses rapidly, with fibrin, hypopyon, retinal phlebitis
  • Reduced risk with prompt wound closure, subconjunctival antibiotics and frequent follow-up
  • Bacilus Cereus 25% of posttraumatic endophthalmitis
  • rapid and severe, often with loss of the eye
  • soil contaminated injuries with IOFB
    •
  • Initial Treatment: anterior chamber and vitreous tap and inject antibiotics
  • Vancomycin 1mg or clindamycin 200 µg intravitreal
  • Ceftazidime to cover gram negatives
    •
  • Pars plana vitrecomy is important to consider early in the course of the infection
    •

     

    Shaken Baby Impact Syndrome

  • Bradycardia, apnea, lethargy, hypotonia, bulging fontanelles
  • Retinal hemorrhages, cotton wool spots, retinal folds, schisis cavities
  • Resembles Terson's syndrome, Purtscher's, CRVO

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    Avulsion of the Optic Disc

     

    Radiation Retinopathy

  • Delayed onset and progressive, microangiopathic changes like diabetic retinopathy
  • Onset can range from 4 months to 3 years from external beam or plaque
  • 30-35 Gy (reported at 15 Gy)
  • Cotton wool spots, hemorrhages, neovascularization, microaneurisms, also CRAO, CRVO, retinal detachment
  • Visual function related to macular involvement

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    Photic Damage

  • Mechanical injury: intense laser irradiance produces vapor and acoustic wave (e.g. YAG laser)
  • Thermal injury: light absorbed to heat (e.g. pan retinal photocoagulation)
  • Photochemical injury: less severe but chronic degeneration, mechanism not understood (e.g. microscope burns)
  • Yellow-white lesion progresses to zone of mottled RPE
  • Hyperfluorescent on angiogram.

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    Solar Retinopathy

  • Gazing directly at sun (or arc welding)
  • Central scotoma, dyschromatopsia, metmorphopsia, headache
  • Vision 20/25- 20/200, recovers in 3-6 months to 20/25- 20/40.
  • Yellow-white spot in fovea, progresses to red dot with pigment halo and in 2 weeks a lamellar hole
  • No Treatment indicated

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    Photocoagulation

    Electroretinogram (ERG)

  • Mass evoked response from the entire retina
  • Entire response <150 msec
  • Uses a corneal contact lens with patient in a perimeter bowl to illuminate entire retina
  • A-wave:
  • negative form
  • rods and cones membrane potentials
  • measured baseline to trough
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  • B-wave:
  • positive form
  • Muller and bipolar membrane potentials
  • Measured trough of a-wave to peak of b-wave.
    •
  • Implicit time
  • time from stimulus to peak of b-wave or
  • time from stimulus to trough of a-wave
    •
  • 5 Common Tests:
  • Scotopic (rod response):
  • dark-adapt the for >20 minutes
  • stimulus is a dim flash, below the cone threshold (rod 1000x more sensitive).
  • No detectable a-wave, prominent b-wave.
    •
  • Photopic (cone response):
  • maintain light-adapted state (to suppress the rods),
  • stimulus is a bright flash.
  • a-wave present, less prominent b-wave.
    •
  • Maximal Combined response:
  • dark-adapt for >20 min,
  • stimulus is a bright flash.
  • Gives maximal response of rods and cones.
    •
  • Oscillatory Potentials:
  • superimposed on the ascending b-wave of a maximal combined response
  • can be filtered out by computer software
  • Represents feedback interactions in the retina.
    •
  • Flicker:
  • Stimulus rate 30 Hz.
  • Rods are suppressed because they can only respond up to 20 Hz (clinically only 8 Hz).
    •
  • Specialized ERG tests:
  • Early Receptor Potential (ERP):
  • A small spike with no latency after intense flash.
  • Correlated partly to the changes in cell membrane potential when lumirhodopsin is converted to metarhodopsin. Primarily a reasearch tool
    •
  • C-wave: late positive spike 2-4 seconds after a stimulus, generated by the RPE
  • Focal and macular ERG:
  • Suppress the rods with bright light and present a rapidly flickering stimulus to create a summated response.
  • A Topographic map can be generated
    •
  • Bright-flash ERG: for opaque media
  • Pattern ERG (PERG): checkerboard stimulus.
  • Measures an average of hundreds of responses.
  • Correlated to Optic nerve/ganglion cell function (eg glaucoma).
  • Test limited by poor reproducibility, degredation by blurred vision, cataract and maculopathy
    •
  • Applications of Full-field ERG:
  • A poor test of macular function.
  • 90% of the total number of cones are outside the macula (even though concentration highest in the fovea). So loss of the entire macula only lowers the cone ERG by 10%.
    •
  • Affected by stimulus intensity, pupil size, area of retina exposed, refractive error (decreased  in high myopia), age (decreased in elderly and newborns until 3-4 months). anesthesia can slightly decrease amplitudes
  • Not affected by cataract or media opacity (brighter flash if dense blood)
  • ERG can distinguish focal disease (better prognosis) and diffuse disease (poorer prognosis).
  • Can be used on family members in hereditary disease to identify carriers (choroideremia)
  • Helpful also in damage from trauma or drug toxicity
  • Chronic retinal capillary loss or vascular insufficency causes abnormalities of the b-wave and oscillatory potentials.