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.
