retina & systemic Flashcards
CAR (cancer-associated retinopathy)
Affects which cells?
Rods < cones
DFE: Arterial narrowing without significant RPE pigmentary alterations. ON can also become atrophic.
Symptoms? Photopsias/nyctalopia/impaired dark adaptation Ring scotoma Central VF loss and VA loss Rapid progression
ERG?
Decreased a=b waves (decreased amplitude)
Antibodies to? (AUTOIMMUNE response to RETINAL ANTIGENS)
Recovern, a-enolase, arrestin,
TULP-1, HSP70
Most common cancers?
Lung (50% small cell), ovarian, colon
Treatment: immunosuppression
Hydroxy/chloroquine
Plaquenil >6.5mg/kg/day
Chloroquine >3mg/kg/day
Increased toxicity w/ age, obesity, liver or renal dx
Findings? Decreased color (red) vision Paracentral scotomas Bull’s eye maculopathy RP-like changes late
Diagnosis? Red 10-2 HVF SD-OCT (loss of IS/OS jn) Multifocal ERG FAF
VA loss may progress even after cessation of the medication.
2011 AAO: s/p baseline evaluation, annual exam starting at 5 years due to the very low risk of developing any toxicity with < 5 years of use (in the absence of other risk factors or unusually high dosages).
Obesity, per se, is not a risk factor for (HCQ) retinal toxicity. However, obese patients are at higher risk of being OVERdosed if the dosage is determined by the weight alone. Instead, the patient should be dosed based on their height and hence “ideal body weight”.
AAO no longer recommends Amsler grid testing due to its poor sensitivity. (aimed at detecting these drug toxicities sooner since by the time they are seen ophthalmoscopically, vision loss has already occurred
Cystinosis
Cornea/conj crystals and retinopathy (patchy).
AR.
ONLY THE NEPHROPATHIC FORM DEMONSTRATES THE retinopathy.
.
Lysosomes cannot excrete cystine Accumulation of intralysosomal cystine)
• Crystals in cornea, iris, lens, retina
– Nephropathic form= Fanconi syndrome= GR, rickets, renal failure, salt and pepper retinopathy
• Tx: cysteamine (systemic for renal, topical for corneal
crystals)
Sickle cell
SS = serious systemic
SS disease results in more serious systemic complications while SC and SThal result in more significant ocular problems.
Remember the “S” in PEPSI’s angoid streaks
Low-intensity photocoagulation to the peripheral ischemic retina may cause regression of the NV and decrease the chance of recurring VH.
DO NOT LASER THE feeder vessels b/c may cause retinal breaks, breaks in Bruch’s membrane, and possible CNV.
Anti-VEGF is not currently the accepted modality
Albinoidism - 2 life threatening conditions (tyrosinase positive; AR) and X-linked ocular albinism
Chediak-Higashi = recurrent infections.
Hermansky-Pudlak syndrome=P: Platelets problems (thrombocytopenia), P: more common in patients of Puerto Rican descent, P = pulmonary fibrosis (major cause of death)
X-linked ocular albinism. Carrier females can be ID by identifying MACROMELANOSOMES on skin Bx. Ocular fundus often shows pigmentary mosaicism in the periphery.
Dietary restriction &/or vitamin supplementation for gyrate atrophy
arginine restriction for gyrate atrophy
(elevated arginine and ornithine levels)
Onset: late childhood. legal blindness if untreated
Gyrate atrophy = ocular crystalline dystrophy
– AR
• DFE: Peripheral paving-stone RPE atrophy coalesce to form scalloped border
• Enzyme defect?
– Ornithine aminotransferase (OAT)
• Elevated serum level?
– ornithine (pathognomonic)
• Symptoms? – Night blindness, progressive VF loss, VA loss • ERG? Decreased • Treatment? – Vit B6, restrict arginine
Can’t gyRAte without your OATs. Can’t stay out late (night blindness) without your vitamin B6, hold the arginine.
Characteristics
(1) the gyrate retinal and choroidal lesions
(2) posterior subcapsular cataracts
(3) high myopia with high astigmatism (e.g. -6 to -10 diopters of myopia)
(4) autosomal recessive pattern
(5) hyperornithinemia (if ornithine levels are normal, another diagnosis should be entertained)
Visual acuity is usually normal in these patients until the age of 10 years.
ILM cells
internal limiting membrane (ILM) = innermost structure of the retina and is made up of footplates of the Muller’s cells (whose nuclei are located in the inner nuclear layer along with bipolar cells, horizontal cells, and amacrine cells).
MAR
Affects which cells?
Bipolar cells
Si: RPE irregularity, retinal arteriolar attentuation, ON pallor
Symptoms?
Photopsias
Night blindness
Peripheral VF loss early
ERG?
classic ERG = “negative ERG” with a near normal A-wave but a markedly diminished B-wave. (also see in CSNB and retinoschisis)
Antibodies to?
Bipolar cells, transducin
vast majority of MAR patients have a known history of melanoma at onset. OCT is generally normal in MAR.
At least some cases of MAR are due to antibodies to the TRPM1 cation transduction channel on bipolar cells.
Treatment: immunosuppression
Negative ERG
negative ERG is seen with congenital stationary night blindness and retinoschisis, MAR, CAR
negative ERG: with a near normal A-wave but a markedly diminished B-wave
Angoid streaks and PXE
Angioid streaks =dark red to brown bands that radiate from the optic nerve = breaks or irregularities in Bruch’s membrane and can lead to: (1) spontaneous SRH that are not necessarily related to choroidal neovascularization (CNV). These subretinal hemorrhages can resolve spontaneously without any evidence of CNV; and (2) CNV – which is the major cause of permanent vision loss in this disorder.
MC systemic condition associated with angioid streaks is pseudoxanthoma elasticum (PXE) (aka Gronblad-Strandberg syndrome!). Other associated conditions include beta-thalassemia, Paget disease of bone, sickle cell anemia, and Ehlers-Danlos syndrome. The mnemonic, “P-E-P-S-I”, can be used to remember some of these associated diseases (the “I” standing for “idiopathic”).
RP + deafness + obesity + endocrine dx?
Alstrom Syndrome (DM, hypertriglceridemia, etc)
AR; ALMS1 gene
Cone-rod dystrophy or RP (like Bardet-Biedl
syndrome)
Si/Sx: tapetoretinal degeneration,
obesity, diabetes, hearing loss, renal failure, and dilated cardiomyopathy. short stature
Unlike the other pigmentary retinopathies, central vision is LOST EARLY in Alström syndrome.
Unlike BBS, there is no polydactyly, hypogonadism, or mental retardation in these patients.
Mnemonic: Alstron is Bardet Biedl’s short fat buddy (both AR also). Has a big heart (dilated cardiomyopathy). Also has diabetes and renal issues given that he is fat.
degenerative retinoschisis
OCT: splits in the middle of the retina
- present in ~4% of normal patients > 40 yo
-usually found in the inferotemporal quadrant in HYPEROPES and occurs bilaterally in 50-80% of affected patients.
Typical and reticular subtype:
1)typical subtype = retinal splitting in the outer plexiform layer (OPL)
2) reticular subtype has splitting in the nerve fiber layer (NFL). RD and posterior extension is more common in the reticular form. Retinoschisis must have both inner and outer holes for a secondary retinal detachment to occur.
2ndary RD Rx options (observation or):
o. Barrier laser retinopexy is appropriate when the retinoschisis is either threatening the macula or is associated with a secondary retinal detachment.
If 2ndary RD and Sx pt: consider
o. SB with cryotherapy would be an appropriate option if a secondary retinal detachment were present and the patient was symptomatic.
o. PPV w/EL and gas tamponade would be an option if a secondary retinal detachment were present and the patient was symptomatic.
- Arises from peripheral cystoid degeneration
- Risk of progression to RD = 3%
Peripheral bone spicules DDx
Bone spicules 2/2 dispersion of pigment in the RPE layer which –> formation of clumps that look similar to the microscopic appearance of bone formation.
DDx:
RP
and other diseases w/diffuse RPE destruction:
old trauma, DUSN, syphilis
BDUMP
Lung Prostate Ovarian Uterine ca –> bilateral Diffuse Uveal Melanocytic Proliferation
Si/Sx: bilateral diffuse thickening of the choroid, serous RD, and cataracts.
choroidal thickening may resemble large choroidal nevi distributed throughout the fundus
Mnemonic: LP OU –> bi DUMP
retinal racemose angioma (aka congenital retinal arteriovenous malformation)
retinal AV malformations, commonly result in poor vision, NO LEAKAGE ON FA, and can be associated with other AVMs of the face and CNS (may be retinal, optic nerve, or brain-related)
abnormally-dilated retinal vessels with abnormal arteriovenous communications (at risk for obstruction and subsequent neovascularization)
developmental malformation by which there is NO INTERVENING capillary bed between some retinal arteries and vein (therefore, RAPID venous filling)
unilateral, sporadic
retinal AV malformations (AVMs) can occur in an isolated fashion, with vascular facial skin lesions (among other areas like the orbit, nasal passages, and mandible),
When facial and/or CNS AVMs also occur= “Wyburn-Mason syndrome” or “Bonnet-Dechaume-Blanc syndrome” or “congenital retinocephalic vascular malformation syndrome” (CRC syndrome).
Racemose angiomatosis: 2/2 dilated arteries and veins, often in all four quadrants, without evidence of vascular leakage.
Intraocular causes of VA loss:
glaucoma 2/2 increased vascular outflow pressure
NV 2/2 ischemic events to the retina, retinal, preretinal and vitreous hemorrhage, as well as sequelae from venous occlusive disease.
DDx = Wyburn Mason. Differentiate by MRI
With an aSx pt and that only a small minority of patients with racemose angiomatosis have Wyburn-Mason syndrome, it is unlikely that neuroimaging would reveal an ipsilateral arteriovenous malformation. However, should do it anyways to R/O.
Encephalotrigeminal angiomatosis
Sturge-Weber syndrome = characteristic fundus lesion is the diffuse choroidal hemangioma. This lesion can give the fundus an increased hyperemic appearance (compared to the fundus of the fellow eye), thus leading to a “tomato catsup” appearance.
OR: “Encephalofacial cavernous hemangiomatosis”
choroidal osteomas
DFE = juxtapapillary, yellow-white lesion with a hint of pigment-clumping and relatively well-defined borders.
-benign tumors typically arising from juxtapapillary choroid
-first seen in adolescent or young adult patients with a slight female predilection
-relatively-flat, lightly pigmented with well-defined or scalloped borders
Sometimes cause CNV -
Various Rx modalities: laser, PDT, anti-VEGF agents to treat CNVMs associated with choroidal osteomas.
Most important Dx characteristic = U/S appearance.
lesion = HIGH reflectivity with shadowing of the orbital contents posterior to it ( “pseudo”-optic nerve)
If you turn the gain down on the ultrasound, this lesion’s reflectivity will persist, while that of the other ocular structures will dissipate.
FA = the dye slowly penetrates the osteoma, and conversely, has difficulty exiting the tumor. Thus, the FA pattern of a choroidal osteoma is typically “SLOW AND LATE”
Serial observation for asymptomatic lesions.
DDx = choroidal hemangioma, choroidal metastasis, amelanotic choroidal melanoma, and choroidal granuloma.
CRVO Dx and Rx
-retinal veins are moderately DILATED and TORTUOUS, while the retinal arteries appear moderately attenuated (consistent with HTN retinopathy)
- IV anti-VEGF therapy can be an appropriate Rx for macular edema and/or retinal/iris neovascularization secondary to a CRVO.
- PRP only if retinal/iris neovascularization PRESENT 2/2 CRVO. DO NOT do if NVE/NVI absent.
Observation = best if no active retinal process (macular edema, neovascularization, etc.) requiring treatment.
congenital hypertrophy of the retinal pigment epithelium (CHRPE) and systemic concern
congenital
typically flat with areas of depigmentation within the lesion (LACUNAE) and/or surrounding the lesion (HALOS).
benign, generally in the peripheral retina, and when typical-appearing can be managed with annual photographs
virtually no potential for conversion to malignant melanoma.
Multiple (often bilateral) smaller “atypical CHRPE” can occur in assoc/w/familial colorectal polyposis as part of Gardner’s syndrome. Gardner’s syndrome would be a legitimate concern in a child or adolescent patient.
DDx: Malignant melanomas (MMs) =typically larger, elevated, do not possess focal regions of depigmentation, and may have associated overlying orange-pigment or sub-retinal fluid. When large, MMs can break through Bruch’s membrane leading to a characteristic “mushroom” shape with the head of the mushroom being the portion of the tumor that has broken through Bruch’s membrane. Choroidal melanomas virtually always arise from the choroid. A choroidal melanoma arising as a metastasis from a skin melanoma is EXCEEDINGLY rare.
Purtscher vs Terson
Purtscher retinopathy: originally described in trauma patients who suffered COMPRESSION injuries to the head and thorax
characterized by LARGE CWS, IRH, and retinal edema usually located around the ON
vision loss may be unilateral or bilateral and may be severe (e.g. worse than 20/200).
no proven Rx
similar DFE = “Purtscher-like retinopathy” (non-trauma) = acute pancreatitis, chronic renal failure, collagen vascular diseases like lupus, and amniotic fluid embolism.
DFE thought to be 2/2 complement activation which results in granulocyte aggregation and leukoembolization.
Main condition confused with this = Terson syndrome = presence of vitreous / sub-ILM / subhyaloid hemorrhage as a result of intracranial hemorrhage (e.g. subarachnoid hemorrhage).
~ 1/3 of patients with subarachnoid or subdural hemorrhage will have Terson syndrome.
Mnemonic: “Tearing” of blood vessels –> intraocular hemorrhage while “Pressure” (e.g. compressive injuries) or “Pancreatitis” would result in Purtscher retinopathy.
Niacin (B3) CME
For the vast majority of causes of CME, a petaloid pattern of leakage would be found on FA.
Nicotinic acid (aka niacin or vitamin B3)= occasionally used as a cholesterol-lowering medication. (shown to inhibit hepatic production of VLDL and its metabolite LDL, and also to increase HDL levels) SE: facial flushing, pruritis, nausea, and paresthesias. Many of these side effects are prostaglandin-mediated and can be minimized by pre-treatment with an oral NSAID.
Nicotinic acid maculopathy: characteristic macular appearance with CME, but NO leakage on FA.
-cystic spaces in the outer plexiform and inner nuclear layers.
The CME in NAM resolves spontaneously over a few weeks with the discontinuation of niacin. Thus, topical NSAIDs and/or steroids are not necessary.
acute macular neuroretinopathy
exceedingly rare disease with only about 60 cases reported in the literature since being initially described in 1975.
females (approximately 85%) in their reproductive years (mean age 27).
Unknown etiology, possible assoc/w/OCP, preceding viral illness, and recent use of stimulants such as epinephrine or ephedrine.
clinical diagnosis marked by the presence of one or more reddish-brown perifoveal round or “wedge shaped” lesions that correlate precisely to the location of the patients’ paracentral relative scotomas.
majority of patients with AMN will recover vision over weeks or months, although there are exceptions
(SD-OCT) and infrared fundus photographs = small fundus lesions are much easier to see & lesions correlate to focal regions of IS/OS disruption and external limiting membrane.
Note that these SD-OCT findings are NOT pathognomonic for AMN and can be seen in many other white dot syndromes and retinal disorders. When combined with the fundus findings and clinical history in this case, however, SD-OCT is helpful to further support the diagnosis of AMN.
Reproductive age female presents with progressive confusion, bilateral subjective visual blurring, and evidence of small vessel arteriolar leakage on FA
3 features of the Susac triad:
- mental status changes (encephalopathy = can manifest with headache [often confused with migraine], confusion, memory problems, ataxia, and personality changes)
- hearing loss (typically bilateral, asymmetric, and sensorineural; can vary from mild/insidious to severe/acute and is typically permanent)
- vision loss from BRAO (can occur at any time during dz; often in small far periphery vessels)
-majority of patients with the syndrome do not exhibit all three features of the triad at the time of presentation.
Susac syndrome is a rare disorder with a female to male predilection of 3 to 1.
typical age at Dx is 20-40 years old.
Hypothesis: immune-mediated injury involving the endothelium of the retina, cochlea and cerebral vasculature.
- retinal arteriole LEAKAGE on FA without retinal infarction (ONLY be seen with FA)
- small or large vessel branch retinal artery occlusions
- Yellowish-white retinal wall “Gass plaques” are virtually pathognomonic in this disease and unlike Hollenhorst plaques DO NOT tend to occur at arteriolar bifurcations.
WIDE ANGLE FA is the preferred screening test for any patient with features suggestive of Susac syndrome.
any patient presenting with subacute hearing loss and retinal arteriole leakage / occlusion probably has Susac syndrome.
MRI of the brain = multifocal T2-hyperintense lesions concentrated in the corpus callosum although present elsewhere throughout the white and grey matter. Much more suggestive of Susac syndrome than MS.
Rx: IV methylprednisolone. Other Rx s/p 1 mo PO pred.
Lupus vasculitis
underlying vasculitis: retinal hemorrhages and cotton wool spots OU
SLE-associated retinal vasculitis occurs in 23% of SLE patients during the initial onset of Sx
increases to 29% during periods of SLE activity after onset
SLE Ab target the antigenic components of MEDIUM-sized blood vessels =pauci-cellular vasculopathy with gradual deposition of HYALINE within the vessel walls.
Unlike GCA, SLE-associated retinal vasculitis does not result in a hypercellular inflammatory reaction with rapid vessel occlusion by endothelial activation, vasospasm and secondary thrombus formation, which can directly occlude large-sized vessels like the central retinal artery. Therefore, SLE-associated retinal vasculitis alone does not account for the development of a CRAO.
However, when antiphospholipid antibodies such as the lupus anticoagulant or anticardiolipin antibodies are present, a hypercoagulable state develops and the retinal circulation becomes predisposed to large-sized vessel thrombus formation. Antiphospholipid antibodies are found in 30% of SLE patients and in 84% of all cases of idiopathic retinal thrombosis. When antiphospholipid antibodies, SLE and retinal thromboses occur together, this entity becomes known as Hughes syndrome.
The historical clue of multiple later-term fetal loss in this case is suggestive for the possibility of antiphospholipid syndrome.
Laser colors
Summary of “preferred” lasers for different retinal pathologies:
Match the colors…
Presence of vitreous hemorrhage: red
Macular edema due to diabetes or vein occlusion: green or yellow
Choroidal neovascularization (general): green or red (especially if blood present)
Coats disease: yellow
In which of the following quadrants are retinal dialyses most often found following blunt trauma?
Blunt trauma may result in a variety of retinal breaks including retinal dialyses, macular holes, giant retinal tears, horseshoe retinal tears, operculated retinal tears, and large, necrotic, sometimes posterior retinal breaks often associated with chorioretinitis sclopetaria.
MC retinal breaks s/p blunt trauma = Retinal dialyses, most often found in the inferotemporal and superonasal quadrants.
All patients with a history of blunt trauma need scleral depression to look for retinal breaks.
Which of the following is the most-commonly administered therapy for cytomegaloviral retinitis?
Oral valganciclovir is currently the most-commonly administered therapy for CMV retinitis.
Less-commonly used therapies include intravitreal ganciclovir, intravitreal foscarnet, and intravenous cidofovir.
What is the presumed etiology of venous obstruction in BRVO?
Systemic HTN –> hardening of the retinal arterioles. At the point where the retinal arteriole and venule cross, they are connected by a common adventitial sheath, which binds them together.
sclerotic arteriole –> deformation of the venule’s lumen, resulting in turbulent blood flow and a blood clot.
retinal cavernous hemangioma FA findings
shows the thin-walled, dilated vascular channels typical of a retinal cavernous hemangioma. Unlike either Coat’s disease or a retinal capillary hemangioma, these lesions do not usually leak on FA. Instead, FA shows a characteristic slow filling of the lesion with pooling of the dye in the upper part of the vascular space. (POOLING)
Mnemonic: what do you have in a big cave? Pooling
FA pattern choroidal hemangioma
large choroidal vessels seen in the arterial phase and late staining of the lesion (LATE STAINING)
Mnemonic: older ppl/late/stains
Remember: DIFFUSE hemangiomas = assoc/w/Sturge Weber syndrome vs. circumscribed ones are NOT. Both types assoc/w/serous RD of retina.
Capillary hemangioma
aka retinal hemangioblastoma
AD or sporadic
rapid arteriovenous phase with massive leakage of dye into the tumor (LEAKAGE)
Mnemonic: young/eager/leaks
reddish-orange vascular tumor fed by a dilated, tortuous retinal artery and drained by an engorged vein.
von Hippel lesions if only in eye, but if CNS and GI involved = von Hippel disease.
VA loss 2/2 serous RD, exudate underneath macula , VH, RD
primary cause of death = cerebellar hemangioblastomas and renal cell carcinoma
phenothiazines
Chlorpromazine (Thorazine) and thioridazine (Mellaril).
Phenothiazines
Chlorpromazine (rare)
Thioridazine >800mg/day
Binds to melanin
Findings?
Pigmentary retinopathy
Lid & conj pigmentation
Stellate anterior capsular cataract
Another cause of stellate ant caps cataract?
Amiodarone
Absorbed in the blood stream –> aqueous. From the aqueous they absorb into the posterior cornea and anterior lens capsule and result in pigment deposition.
In the retina, chlorpromazine rarely causes damage. At doses normally used (<800 mg/day) thioridazine rarely causes retinopathy. But THIORIDAZINE can result in severe retinopathy with high doses. Initially there is RPE stippling in the posterior pole. It then progresses to RPE loss in a nummular (coin-shaped) pattern. Immediate cessation of the drug is indicated when retinopathy is detected.
pseudoxanthoma elasticum (PXE) (aka ?)
Gronblad-Strandberg syndrome!
Hughes syndrome
When antiphospholipid antibodies, SLE and retinal thromboses occur together, this entity becomes known as Hughes syndrome.
Mnemonic - Pretty in pink = John Hughes syndrome = lupus invited to the party (phospholipid antibodies) - clots everywhere
Wyburn-Mason syndrome
sporadic condition characterized by ipsilateral AVM involving the brain (especially the midbrain), retina, and occasionally facial skin
rare condition, with a recent review finding only 52 reported cases
Racemose angiomatosis must be distinguished from Wyburn-Mason syndrome, which is best done with MRI imaging or cerebral angiography.
or “Bonnet-Dechaume-Blanc syndrome” or “congenital retinocephalic vascular malformation syndrome” (CRC syndrome).
Retinitis pigmentosa
Retinitis Pigmentosa (RP) ERG = most critical measure b/c it documents the diffuse photoreceptor damage that defines RP
2 types?
type 1 rod-cone; type 2 cone-rod
Si/Sx: Early onset nyctalopia, midperipheral scotomas (eventually becomes ring scotoma)
Most RP patients have mild tritan (blue-yellow) color deficiency
Clinical Findings?
Triad: waxy ON pallor, peripheral bone spicules, narrowed arterioles
Also:
pigmentation is variable
many patients have few/or no bone spicules
Pigmented vitreous cell
Macular edema w/o leakage on FA
PSC
Associated with myopia (unlike LCA associated with hyperopia)
HVF: mid-peripheral scotomas, eventually becomes ring scotoma
Late finding in RP: small tubular fields. NOT pathogomic
ERG?
Decreased amplitude (A & B waves)
Increased implicit time
ERG decreases 50% every 7yrs (w/o treatment)
Associated with myopia (unlike LCA associated with hyperopia)
Dietary restriction &/or vitamin supplementation for homocystinuria
methionine restriction / high cysteine / vitamin B6 supplementation for homocystinuria
Dietary restriction &/or vitamin supplementation for abetalipoproteinemia (Bassen Kornzweig)
RP + hereditary abetalipoproteinemia
AR
Deficiency in fat soluble vitamins (ADEK)
Eyes: Atypical RP (sine pigmento), Bitot’s spot on
conjunctiva, xerophthalmia, coagulopathy
Systemic: Poor vitamin A absorption & steatorrhea
Also: ataxia, acanthocytosis
• Other causes of treatable RP due to vit A def: chronic
pancreatitis, cirrhosis, bowel resection
Treatment?
Low fat diet, vitamin A + E supplement
Dietary restriction &/or vitamin supplementation for Refsum disease
RP + phytanic acid oxidase deficiency (w/elevated phytanic acid) RAIN = RP Ataxia Ichthyosis Neuropathy
Inheritance: AR (7q21-22; PEX1), long chain fatty acid metabolism
Labs: High phytanic acid, copper & ceruloplasmin
– Atypical RP (sine pigmento); enlarged K nerves
Also:deafness, anosmia, cardiomyopathy, symmetric short 4th toes
– Dx: Increased serum copper and ceruloplasmin
– Tx: phytanic acid restriction therefore dietary restrictions of animal fats, milk products, leafy green vegetables
Tyrosinase negative
AR, decreased melanin
Oculocutaneous
• Tyrosinase negative (no pigmentation)
– Ocular: iris tranilluminations, foveal hypoplasia, hypopigmented fundus, nystagmus, photophobia, high myopia; cutenous: white hair, pink skin
salt and pepper fundus DDx
rubella leber congenital amaurosis Congenital syphilis CPEO • Carriers: – Albinism – Choroideremia – RP
Congenital problems: rubella, syphilis, leber’s. CPEO.
Carriers: CRAP: choroideremia retinitis (albnism) pigmentosa
Other names for Wyburn-Mason syndrome
When facial and/or CNS AVMs occur with retinal racemose angioma= “Wyburn-Mason syndrome” or “Bonnet-Dechaume-Blanc syndrome” or “congenital retinocephalic vascular malformation syndrome” (CRC syndrome).
DDx for shunt vessels
vein occlusion
optic nerve gliomas and meningiomas
chronic papilledema
glaucoma (?)
usually takes 6-12 months before shunt vessels form after a CRVO.
Retinitis Pigmentosa
with systemic associations
Bardet-Biedl
Usher syndrome
Kearns-Sayre
Bassen-Kornzweig (abetalipoproteinemia)
Refsum’s disease (elevated phytanic acid)
Gyrate atrophy (elevated arginine and ornithine levels)
Bardet-Biedl
RP + polydactyly + obesity (Bardet-Biedl)
RP + spastic paresis (Laurence-Moon)
Both: short stature, hypogonadism, mental retardation, urethral reflux / pyelonephritis
Inheritance: AR (Ch 16); likely multigenic
– salt & pepper retinopathy
– Flat/decreased ERG
Usher syndrome
RP + deafness
AR (Ch 1q41; USH2A); Cilia defect (photoreceptors & hair cells)
– Sensorineural hearing loss, variable vestibular
dysfunction, Also: ataxia, MR, low phosphate (rickets)
– differential in an infant/child suspected of rubella
– Tx: cochlear implants
RP + deafness + obesity + endocrine dx? Alstrom Syndrome (DM, hypertriglceridemia, etc.)
CPEO / Kearns-Sayre
RP + CPEO (EOM limitations + ptosis)
Mitochondrial myopathy
– CPEO - symmetric ophthalmoplegia and ptosis (no
diplopia)
Also: heart block (Kearns-Sayre)
Path findings: ragged red fibers on muscle bx
Treatment?
Coenzyme Q10
Congenital Stationary Night Blindness
CSNB
Prolonged recovery of normal rhodopsin levels after light exposure
• Night blindness for several hours to dark adapt
• Paradoxical pupil
– Pupil constricts in dark after exposure to light
• ERG?
– Rod ERG decreased but normalizes after prolonged dark adaption
– Negative ERG
• Fundus albipunctatus
• Oguchi disease Fundus findings?
• Mizuo-Nakamura phenomenon
• Mizuo-Nakamura phenomenon
– Yellow sheen fundus appears normal after dark adaptation
-seen in Oguchi disease
Fundus albipunctatus
form of CSNB • AR • Nyctalopia • Good acuity/color, but slow prolonged dark adaptation • deep yellow-white spots spare macula
– Differentiate from Retinitis punctata albescens (RP variant has narrowed vessels and ERG does not improve
with dark adaptation)
Also differentiate from Alports
Alports syndrome
– AD, retinal appearance similar to fundus albipunctatus
– kidney failure with deafness
– anterior lentoconus and ant polar cataract
Retinitis punctata albescens
RP variant • Looks like fundus albipunctatus • BUT narrowed vessels • Depressed ERG with loss of rods – Does not renormalize with dark adaptation
Oguchi disease
Prevent rhodopsin from being stimulated
• Mutation in recoverin protein
• Mizuo-Nakamura phenomenon
– Golden brown fundus (yellow/gray sheen) in
light adapted state normal colored fundus
in dark adapted state
Crystalline Dystrophies (Systemic)
–Primary hereditary hyperoxaluria
– Cystinosis
– Secondary oxalosis
– Sjögren-Larsson syndrome (type of ichthyosis)
Crystalline Dystrophies -Drug Induced
– Tamoxifen – Canthaxanthin – Talc – Nitrofurantoin – Secondary oxalosis • Methoxyflurane anesthesia • Ethylene glycol ingestion
Crystalline Dystrophies - Ocular
– Beitti crystaline dyst.
– Calcific drusen
– Gyrate atrophy
– Retinal (juxtafoveal) telengectasia
Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHAD)
•d/o mitochondrial fatty acid betaoxidation
• Normal at birth, later chorioretinal atrophy and occlusion of choroidal vessels
• Tx: low-fat, high carbohydrate diet with carnitine
supplementations
• Prognosis: fatal by 2 yrs of age (hepatic or cardiorespiratory failure) unless dietary treatment
is started
• How to distinguish from retinoschisis RD?
In retinoschisis (a splitting of the neurosensory retina)
- Absolute scotoma (vs. relative in RD)
- Blanches with laser (+rxn)
- Associated with hyperopia
- Smooth, bullous, dome-shaped appearance
- rare/no Shafer sign/VH
- inferotemporal location
- absence of shifting fluid and absence of corrugation.
combined hamartoma of the retina and RPE
rare usually unilateral congenital malformation of the retina and RPE
predominantly affects males
elevated grey-brown mass
no vitritis
on FA can see pinpoint leakage
elevated hyperreflective mass in retina with underlying attenuation of the outer retina and photoreceptor layers
underlying retina appeared to be disorganized and thick lwith loss of normal foveal contour
location is usually peri-papillary along arcades
DDx choroidal malingant melanoma choroidal nevus CHRPE choroidal osteoma
Torpedo maculoapthy
congenital abnormality of RPE clinically manifesting as an asymptomatic well-circumscribed hypopigmented macular lesion temporal to the fovea with a torpedo-like tip directed towards the foveola
originally thought to be nevus, but now shown to be persistent defect in the development of the RPE
2010 - Shields stated it could represent a persistent defect in the development of the RPE in the fetal temporal bulge
CLasically, torpedo shape with tip pointing to the center
hyperluorescence on FA 2/2 window defect
Cleft with a thin abnormal RPE signal
abnormal material on the back of a thin retina with degenerated photoreceptors and loss of outer segments
hyporeflective space and increased signal transmission into the choroid
solar retinopathy
Risk factors
(a) younger age; (b) clearer lenses; and (c) drugs that photosensitize the eye like psoralen or tetracycline.
Psoralen may be taken orally in the treatment of extensive vitiligo or other skin disorders. Psoralen may be used in conjuction with UVA phototherapy (PUVA-Psoralen UVA) for some skin conditions.
Protective: darker fundus pigmentation and high refractive errors.
initial DFE =no signs or yellow-white dot (retinal edema)
After a few days: reddish dot - may evolve into a lamellar hole or depression.
FA: demonstrate a window defect which corresponds to this thinned area.
Tay Sachs
seizure disorder, mental retardation, poor swallowing ability, and an increased startle reflex to noise
cherry-red spot 2/2 accumulation of ganglioside GM2 in the ganglion cells surrounding the fovea
defect in the hexosaminidase A enzyme.
Laurence-Moon syndrome (LMS) vs Bardet-Biedhl
There is some overlap between BBS and some authors consider them to be on the continuum of the same syndrome. Classically however, LMS features spastic paraplegia and does NOT have polydactyly.
Laurence Moon is Bardet Biedhl’s brother with paraplegia - polydactyly
Familial amyloidosis
MC 2/2 transthyretin mutation
peripheral neuropathy, autonomic neuropathy (e.g. gastrointestinal symptoms like diarrhea), and cardiomyopathy.
vitreous infiltration by amyloidosis is frequently VISUALLY significant (unlike asteroid hyalosis)
Familal amyloidosis, caused by transthyretin mutations, also commonly presents with increased intraocular pressure.
sectorial retinal degeneration
sharp demarcation between affected and unaffected retina. The trait that distinguishes this entity, sectorial retinitis pigmentosa, from other causes of retinal hyperpigmentation (e.g. trauma, past inflammation) is its presence in both eyes.
Evidence that this sectorial loss is caused by light toxicity in individuals with rhodopsin mutations. Therefore, UV-protection and antioxidants are often recommended.
retinitis pigmentosa sine pigmentum
While unusual, RP can occur without bone spicule formation
Bone spicules result from dispersion of pigment in the retinal pigment epithelial layer which leads to the formation of clumps that look similar to bone under the microscope.
Usually these cases of RP sine pigmentum have other fundus findings typical of RP including waxy pallor of the optic nerve and attenuated arterioles.
Also, bone spicules can occur in many other disease causing destruction of the retina (e.g., old trauma, DUSN, syphilis, etc).
CMV retinitis vs. HIV retinopathy
Unless there is obvious signs of CMV retinitis (e.g. large area of necrosis with overying hemorrhage), its differentiation from HIV retinopathy requires determining whether any enlargement of the retinal lesions has occurred. This is typically achieved with serial fundus photographs.
It also is helpful to obtain a CD4 count to stratify the patient’s risk for developing this opportunistic infection. Obtaining CMV serologies is not helpful since most people in the general population are CMV positive.
CWS > 750 um likely early CMV retinitis in unknown CD4 count (look at lesions over 1-2 weeks if unsure)
CMV spreads along vessels (perivascular), endothelium
bilateral retinal neovascularization DDx
diabetes mellitus, branch retinal vein occlusion (BRVO), sickle-cell retinopathy, Eales’ disease, or from inflammatory conditions such as sarcoidosis, tuberculosis (TB), Behcet’s disease, peripheral uveitis, or systemic lupus erythematosus (SLE).
Workup should be directed toward these diagnoses and should include a serum glucose and/or glucose tolerance test, fluorescein angiography (for BRVO), hemoglobin electrophoresis (for sickle-cell retinopathy), chest xray (for TB, sarcoid), ACE titer (for sarcoid), ANA titer (for SLE), HLA-B5 (for Behcet’s disease), and a tuberculin skin test with anergy panel (for TB and sarcoid).
DDx of sub hyaloid/sub ILM hemorrhage
Terson Valsalva high altitude diseases causing NV Leukemia
ERG for RP
Decreased amplitude (A & B waves)
Increased implicit time
ERG decreases 50% every 7yrs (w/o treatment)
Spielmeyer-Vogt-Batten-Mayou
RP + neuronal ceroid lipofuscinosis
Lipofuscin accumulates in lysosomes
Also: seizure, dementia, ataxia, vacuolization of peripheral lymphocytes
Inheritance: AR, usu. Jewish girls
Idiopathic Polypoidal Choroidal Vasculopathy (IPCV or PCV)
Multifocal, recurrent serous PEDs
Saccular choroidal outpouchings
More common in?
African-Caribbeans & Asians (accounts for >30% of exudative maculopathy in Asian populations)
FA?
Early hyperfluorescent polyps and hypofluorescent halos
Polyps better seen on ICG
Treatment?
Anti-VEGF, PDT, or combined
Only disease in SUMMIT trial to have improved response to combined anti-VEGF + PDT
Sickle Cell Hemoglobinopathy?
SC worst ocular Sx (SC>Sthal>SS>SA)
SS worst systemic Sx
Gene defect?
Val sub for glu acid at 6th position on B-polypeptide chain
Avoid carbonic anhydrase inhibitors
Other Eye findings?
Angioid streaks
Comma sign (segmented conj vessels)
Sickle Cell nonproliferative
Nonproliferative Salmon patch Intraretinal hemorrhage after arteriolar occlusion Iridescent spots Old resorbed heme Black sunburst RPE hypertrophy, hyperplasia
Sickle Cell Treatment?
Treatment?
Scatter laser to ischemic retina
PPV precautions (avoid encircling SB or taking down EOMs, avoid epi in local anesthetic, ensure O2 & hydration)
Sickle Cell Proliferative?
Stage 1: peripheral arteriolar occlusion Stage 2: peripheral AV anastomoses Stage 3: preretinal sea fan NV (posterior border of nonperfusion; may autoinfarct and turn white) Stage 4: Vitreous hemorrhage Stage 5: Tractional RD
RP Inheritance and treatment?
AR (most common) -70%
most recessive RP has not been genetically defined.
Sporadic
10% AD (least severe; rhodopsin– Ch3, most common mutation P23H; RDS/peripherin). rhodopsin gene abnml in only ~30% of dominant RP
10%XR (least common, earliest onset, fastest progression, worse prognosis)
Treatment?
Vitamin A, NOT vitamin E, lutein, DHA, oily fish
Sector RP
RP in part of retina (usu. Inferotemporal)
RP sine pigmento?
RP without RPE changes
Retinitis punctata albescens
RP + white spots
Inverse RP
RP in macula
Spielmeyer-Vogt-Batten-Mayou
RP + neuronal ceroid lipofuscinosis
Lipofuscin accumulates in lysosomes
Also: seizure, dementia, ataxia, vacuolization of peripheral lymphocytes
Inheritance: AR, usu. Jewish girls
Cone dystrophy
Inheritance: variable
Onset usually in teens
Symptoms?
Progressive central VA loss
Hemeralopia (day blindness)
Photophobia
Fundus findings? Bull’s eye maculopathy Optic pallor Vessels NOT attenuated; unlike rod dystrophies like RP May involve rods later in life
Goldmann-Favre Syndrome
No rods, cones doubled (92% S-cones)
Similar to RP + juvenile retinoschisis
Clinical features? Night blindness & blue light sensitivity Nummular yellow lesions along arcades (not pigment spicules like RP) Macular schisis (no leakage on FA) ON pallor & attenuated vessels Optically-empty vitreous
Inheritance?
- AR (defect in NR2E3 transcription factor)
How to distinguish from X-linked retinoschisis?
Both ERG/EOG abnormal
(EOG normal in X-linked retinoschisis)
Tamoxifen/Xanthines
Tamoxifen >200mg/day
Canthaxanthine (rare)
(carotenoid for tanning)
Talc
Secondary oxalosis
Ethylene glycol
Methoxyflurane
Findings?
Crystalline retinopathy
Outer retinal defect
Except tamoxifen, others usually reversible when drug is stopped
Desferoxamine toxicity
Ring scotoma
Pigmentary retinopathy
Decreased ERG
Isotretinoin toxicity
Nyctalopia
Decreased ERG
Reversible
Rifabutin toxicity
Anterior & posterior uveitis
Gentamicin toxicity
Macular atrophy
Occurs with intracameral use after phaco in post-PPV pts
Sildenafil SE
Blue vision
ERG changes
Reversible
Digitalis SE
Yellow vision (xanthopsia)
Pericentral scotoma
Decreased acuity, color vision
Reversible
Bietti crystalline dystrophy
Inheritance: AR (CYP4V2) Marginal corneal dystrophy Crystalline retinopathy Choroidal sclerosis Progressive night blindness VF constriction
