Title: Optic Atrophy
Author: Sean Collon, MSIV, Vanderbilt University School of Medicine
Photographer: James Gilman, CRA, FOPS
Keywords/Main Subjects: Optic atrophy; glaucoma; optic neuropathy; hereditary optic neuropathy
CORE Category: Med Student Outline; Anatomical Approach to Eye Disease; Optic Nerve; Optic Atrophy
Optic atrophy is a term that describes the finding of a pale optic nerve head, indicating the death of retinal ganglion cells due to injury at some point along their course from the retina to the lateral geniculate nucleus. It represents the end stage of an underlying pathologic process, typically developing 4-6 weeks after onset of symptoms in most optic neuropathies, even after recovery of some or all vision. Because there is currently no way of regenerating retinal ganglion cells in humans, vision loss due to optic atrophy is permanent.
Optic atrophy is diagnosed by the visualization of a pale optic disc on fundoscopic evaluation and may be accompanied by findings suggestive of the underlying etiology, such as cupping or papilledema. On the other hand, the classic triad of vision loss, relative afferent pupillary defect, and pale disc yields a vast differential that includes:
- Inflammation/Infiltrative process: sarcoid, lupus, multiple sclerosis, lymphoma/leukemia
- Infection: herpes, TB, syphilis
- Ischemia: arteritic versus non-arteritic ischemic optic neuropathy, diabetes
- Intraocular: glaucoma
- Intraorbital: tumor, optic nerve glioma, thyroid eye disease
- Extraorbital: meningioma or some other intracranial tumor or mass
- Toxic/Metabolic Causes: B12 deficiency, medications (e.g. ethambutol, amiodarone), methanol ingestion, heavy metals
- Trauma: traumatic optic neuropathy
- Hereditary Causes: Autosomal dominant optic atrophy, Leber’s hereditary optic neuropathy
The workup for a patient with optic atrophy has two primary goals: to assess the extent of damage/ remaining visual potential and to identify and remove the underlying etiology to preserve remaining vision.
Optic nerve function can be assessed with visual acuity, color vision testing, and quantitative perimetry. Optical coherence tomography (OCT) can be used to establish and monitor retinal nerve fiber layer (RNFL) thickness, but can be confounding in cases of optic atrophy due to papilledema, where RNFL thinning may mimic resolution of papilledema. Finally, fundus photography can be helpful in documenting the extent of atrophy and monitor changes in the pattern of atrophy over time.
Patients will often present with signs or symptoms that suggest a specific etiology, and testing should be tailored accordingly. For the patient with otherwise undifferentiated optic atrophy, initial workup should include MRI of the brain and orbits with gadolinium contrast, blood work including CBC, CMP, folate, B12, heavy metals and inflammatory markers such as ESR, CRP in the elderly. If no cause is identified and the patient remains stable symptomatically, observation may be reasonable. However, if symptoms worsen or recur, further workup is indicated.
Images or video:
Summary of the Case: Optic atrophy is the finding of a pale optic nerve head, which indicates the death of retinal ganglion cells from any of a number of causes, including inflammation, infection, ischemia, compression, toxicity, trauma, or hereditary conditions. Management consists of identifying and treating the cause of optic nerve damage and preserving what vision remains.
- Osaguona VB. Differential diagnoses of the pale/white/atrophic disc. Community Eye Health. 2016;29(96):71-74.
- Girkin CA. 2016-2017 Basic Clinical Science Course, Section 05, Neuro-Ophalmology. San Francisco, CA: American Academy of Ophthalmology, 2017. Web. 17 Aug 2018.
Faculty Approval by: Griffin Jardine, MD
Copyright Sean Collon, ©2018. For further information regarding the rights to this collection, please visit: http://morancore.utah.edu/terms-of-use/
Title: Light-Near Dissociation
Author: Robert Henseler, 4th Year Medical Student, Rutgers University – New Jersey Medical School
PERRLA or Pupils Equal, Round, Reactive to Light and Accommodation might be the most common acronym to be seen in medical records on the physical exam. Unfortunately, many physicians do not properly asses all aspects of the acronym, so it is very possible to miss subtle changes in the pupils. To discuss light-near dissociation it is important to first have a discussion on the pupil itself and why it constricts. There are two main reasons for constriction, the first is due to stimulation by light (pupillary light response) and the second is due to accommodation or when a patient focuses on a near object.
Anatomy and Pathways:
For the pupillary light response, increased light on the retina leads to miosis or constriction of the pupil and less light leads to mydriasis or dilation of the pupil. The sensory input travels through the optic nerve (CN2) to the pretectal nucleus where it then travels to both Edinger-Westphal nuclei. It then travels to the oculomotor nerves (CN3) and to the ciliary sphincters where it constricts both pupils. This is what leads to direct (stimulated) and consensual (contralateral) pupil constriction.
Accommodation is slightly more complicated and actually consists of three actions. The pupil constricts (due to a similar pathway as above including the Edinger-Westphal nuclei), the lens shortens allowing the eyes to focus (due to relaxation of the zonular fibers due to action of muscles within the ciliary bodies), and the eyes converge on the object (meaning turn in via contraction of the medial rectus muscles).
During the physical exam it is important to do a thorough pupillary exam as abnormal responses can be diagnostic clues to potentially serious pathology. In a dark room observe the size of the pupils. Holding a pen light at a slight angle below the face allows for easy visualization of the pupils without the light hitting the retina and causing constriction of the pupils. The first step is to check the light reflex. Shine light individually into each eye twice. First watching for the direct response (constriction of the ipsilateral pupil) and next looking for the consensual response (constriction of the contralateral pupil). Reflexes should be brisk. A swinging light test, shining light from one pupil to the next can then be done to check for a relative afferent pupillary defect (RAPD). RAPD and its causes is described in more detail in another section. Following the light response, the physician should check that the pupils constrict on accommodation. In a dimly lit room have the patient look at your finger from 3-4 feet away and then move your finger towards their nose as the patient follows your finger observing the convergence of the eyes and the constriction of the pupils.
In light-near dissociation there is slow or incomplete pupillary light reflex, but the pupil will still constrict during accommodation.
So what does light-near dissociation mean clinically and what should be done diagnostically? There are a few entities to consider. Historically speaking this was very commonly seen with neurosyphilis. Hence the origin of the politically incorrect term, “prostitute’s pupil”. This specific diagnostic term is Argyll Robertson Pupil. In the developed world this has become extremely rare due to increased access to care, advancements in blood testing, and the use of antibiotics to treat syphilis in its early stages before it progresses to neurosyphilis. Regardless, a patient with a light-near dissociation should be worked up for syphilis, with appropriate history, physical exam, and bloodwork.
Adie’s or Tonic pupil is probably the most common cause of light-near dissociation. It is a disorder in which one, (or possibly both) pupils are abnormally dilated. The light response is slowed. It is due to injury to the parasympathetic oculomotor nerve. In the acute stages the reaction to accommodation can be delayed as well, but chronically light near dissociation is common. Also, chronically the pupil tends to get smaller in size due to regeneration of nerve fibers to the iris sphincter. Adie’s pupil is generally considered a benign condition and might not require further workup. Interestingly, Adie’s pupil is associated with hyporeflexia, especially of the knee and ankle reflexes (Adie’s Syndrome). Adies pupil can also be seen in diabetes, Sjogrens syndrome and other autonomic disorders.
Lastly, a more rare cause of light near dissociation is Parinaud Syndrome. This syndrome is characterized by paralysis of upward gaze, light-near dissociation, eyelid retraction, and convergence retraction nystagmus. If these signs are seen it is important to work up the patient for Parinaud Syndrome and its multiple causes, which are all connected in that they involve direct or indirect injury to the structures involved in the pathway including the Edinger-Westphal nucleus in the midbrain of the brainstem. Pineal tumors leading to compression of nearby structures are the most common cause of Parinaud Syndrome so appropriate brain imaging should be done. Multiple sclerosis (MS) is another cause, so anyone suspected of MS should have a full workup. Lastly, stroke can cause direct injury to the midbrain.
Light-near dissociation detection requires a thorough pupillary exam by a physician. While rare, it can be a sign of serious pathologic conditions and more work-up and testing should be performed for anyone found to have this pupillary finding.
Author: Kaitlin Smith, 4th Year Medical Student, University of Missouri School of Medicine
Anisocoria is defined as unequal pupil sizes—occasionally first noticed by a clinician but more commonly detected by the patient and brought to the clinician’s attention. The difference in size between two pupils should not typically be greater than 0.4 mm, therefore most any change that the patient or clinician notices would be abnormal—whether due to a benign or malignant etiology. Some of the associated causes of anisocoria have life-threatening implications. Thus, we hope to layout a framework and approach to assist in the triage and management of these patients.
Pertinent questions should include:
- Timing of Onset: Ask the patient for photos that precede the suspected date of onset as anisocoria can be noticed suddenly but may truly be longstanding or even congenital.
- History of trauma: Inquire about trauma specifically to the eye, head or neck.
- Social history: Determine if the patient has factors that would predispose them to lung pathology such as smoking.
- Medical history: Ask about strokes, sexually transmitted diseases (Syphilis), glaucoma or rheumatologic conditions.
- Current medications: Inquire specifically about medications with autonomic effects (e.g. scopolamine patch).
The pupils should be examined for shape, position, symmetry, reactivity, and size. Size is most easily determined with the help of a measurement tool that includes millimeter increments, included in many near acuity cards (Figure 1). Size of the pupil should be recorded in both light and dark conditions with the patient focusing on a target in the distance to avoid pupillary constriction associated with viewing targets at near (accommodation and the near triad). The pupillary response should also be observed at near to determine if the patient has a light-near dissociation. A halogen light is typically used to determine both direct response (the constriction of the pupil the light is being shone into) and consensual response (the constriction of the contralateral pupil when light is shone into the ipsilateral eye). The healthy pupil constricts to 2-4 mm in size when exposed to light and will dilate up to 4-8 mm in the dark.
The key to the pupillary exam in anisocoria is identifying whether the anisocoria is greater in light or dark conditions—this clues you in to which part of the autonomic system is affected. The sympathetic system dilates the pupil while the parasympathetic system constricts the pupil. Image 1 demonstrates one example of how to test and evaluate anisocoria.
Acute Angle Closure Glaucoma
A fixed mid-dilated pupil associated with significant eye pain and redness suggests acute angle closure glaucoma. Checking the intraocular pressure (IOP) via a portable handheld pressure reading device, such as a Tono-pen®, would rule this in or out.
Sudden Onset 3rd Nerve Palsy
Anisocoria greater in light suggests an abnormally large pupil with impaired constriction or disrupted parasympathetic innervation. The parasympathetic fibers innervating the pupil travel with the 3rd cranial nerve, or oculomotor nerve. A sudden-onset dilated pupil associated with a droopy eyelid (ptosis) and abnormal eye position (strabismus – typically down and out) is highly suggestive of an acute 3rd cranial nerve (oculomotor) palsy. This could be caused by a potentially life-threatening posterior communicating artery aneurysm or impending uncal herniation. This presentation warrants immediately sending the patient to the emergency room for neuro-imaging and evaluation.
Sudden Onset Horner’s Syndrome
A Horner’s syndrome is characterized by anisocoria greater in dark, meaning an abnormally small pupil with impaired dilation or disrupted sympathetic innervation. It is often, though not always, part of a triad of signs, the other two being an ipsilateral droopy eyelid (ptosis), and lack of sweating (anhidrosis). The diagnostic challenge of a Horner’s Syndrome is that the lesion can be located anywhere along the sympathetic pathway. The most urgent and life-threatening etiology is a carotid artery dissection, but other serious causes may include a malignant lung tumor or spinal cord injury. Patients with an acute-onset Horner’s Syndrome need urgent imaging of the head, neck and upper lung that would include a study capable of detecting a carotid artery dissection, such as an MRA or CTA. Timely identification and treatment of a carotid artery dissection—including anticoagulation—can prevent a potential embolic stroke.
Over 20% of cases of anisocoria are the same in light and dark conditions and are benign, thus deemed, “physiologic anisocoria.” This condition typically presents with intermittent pupillary differences of less than 1 mm that are unchanged from light to dark and may be sporadic. It is thought to be caused by unequal inhibition of the parasympathetic pathway.
Anisocoria is an important exam finding that can be detected by an astute clinician who performs a careful and methodical pupillary exam. It is crucial for providers to be aware of the diagnostic steps to narrow a differential for anisocoria, as it can be a harbinger of treatable but life-threatening conditions. Below are two tables that include a broader differential for anisocoria.
Table 1: Anisocoria caused by parasympathetic defects
|Adie’s tonic pupil||Idiopathic decrease in parasympathetic stimulation||Usually benign. Routine follow up in clinic with an ophthalmologist.|
|Trauma||Injury to the dilating muscles of the iris||If there is concern for head trauma, ruptured globe, hyphema or orbital fracture; consider obtaining CT and consulting ophthalmology.|
|Oculomotor nerve palsy||The parasympathetic fibers run on the outer portion of the nerve and thus are the first to be damaged in any compressive injury to the nerve.||CT and MRI should be obtained to rule out posterior communicating artery aneurysm, uncal herniation or an intracranial tumor. Urgent consultation and referral to neurology is typically warranted.|
|Pharmacologic Dilation||Agents such as scopolamine patches, inhaled ipratropium, nasal vasoconstrictors, and Jimson weed inhibit parasympathetics or activate sympathetics.||Non-urgent. Can typically be managed without referral. Determined by thorough history. Stop offending agent if causing light sensitivity and non-essential medication.|
Table 2: Anisocoria caused by sympathetic defects
|Horner’s syndrome||Lesion along the sympathetic pathway from hypothalamus to lung to carotids. Common signs: constricted pupil & slight eyelid droop unilaterally. Less common signs: Lack of sweating and erythema unilaterally.||Urgent to determine location of the lesion with imaging along the sympathetic pathway or referral to an ophthalmologist as the cause can be life threatening.|
|Argyll-Robertson pupil||Bilateral pupils that constrict when viewing an object at near, but not with light stimulus typically due to tertiary syphilis||Obtain testing for syphilis (FTA-ABS). Would likely warrant admission for IV antibiotics to treat neurosyphilis.|
|Iritis||Inflammation in the eye can lead to adhesions from the pupil to the lens, causing impaired dilation.||Warrants urgent follow up in clinic with an ophthalmologist unless there are signs of acute angle closure glaucoma.|
|Pharmacologic Constriction||Agents such as pilocarpine, prostaglandins, opioids, clonidine, and organophosphate insecticides inhibit sympathetics or activate parasympathetics.||Non-urgent. Can typically be managed without referral. Determined by thorough history. Stop offending agent if bothersome to patient.|
- Demyelinating Optic Neuritis – EyeWiki. http://eyewiki.aao.org/Anisocoria. Published February 13, 2016. Accessed July 16, 2018.
- Gross JR, Mcclelland CM, Lee MS. An approach to anisocoria. Current Opinion in Ophthalmology. 2016;27(6):486-492. doi:10.1097/icu.0000000000000316.
- Ronquillo N. Anisocoria. Moran Eye Center Resident Lectures. June 2018.
- DonRaphael W. Pupils – Approach and Cases. Moran Eye Center Resident Lectures 2017. June 2018.
- Foroozan R, Vaphiades M. The pupil. In: Kline’s Neuroophthalmology Review Manual . 8th ed. NJ: SLACK Incoporated; 2018:129-142.
Topic: Orbital Rhabdomyosarcoma
Author: Colton McCoy, MBA, Texas Tech University Health Sciences Center School of Medicine
Ocular RMS is a broad term that describes RMS occurring in the orbit, conjunctiva, anterior uveal tract, or eyelid. RMS can occur in many places throughout the body and comprises 4% of pediatric malignancies, with 10% of all RMS cases occurring within the orbit . Around 250 new cases of RMS occur each year . Rhabdomyosarcoma (RMS) is the most common primary malignant tumor of the orbit in children with a mean age of onset of 5-7 years old . Although most cases of orbital RMS occur early in childhood, the disease has been reported from birth into the eighth decade of life. This is a life-threatening tumor and as such requires prompt diagnosis and treatment.
Orbital RMS can arise within the orbit (primary), can occur from direct extension from adjacent areas such as the nasopharynx (secondary), or after spread to the orbit from distant organs (metastatic). Primary orbital RMS was initially posited to originate from striated skeletal muscle of the orbit. However, it is now known that among the different histologic variants of RMS, the majority of cases find origin in pluripotent mesenchymal cells which retain the ability to differentiate into striated muscle . This most common type of orbital RMS is referred to as embryonal RMS and is what will occupy the majority of this review.
Most cases of orbital RMS are located in the superonasal orbit. Thus, the hallmark presentation of orbital RMS is a rapidly occurring proptosis (80-100%) with inferotemporal displacement of the globe (70%) due to mass effect . Patients may also present with blepharoptosis (30-50%), conjunctival and eyelid swelling (60%), palpable mass (25%), pain (10%), vision loss, or signs of sinusitis . Rarely, orbital RMS can metastasize hematogenously to other organs (bone, bone marrow, lungs) or invade locally.
- Orbital Cellulitis
- Idiopathic orbital inflammation
- Dermoid cyst
- Langerhans cell histiocytosis
- Other sarcomas
- Metastatic neuroblastoma
A thorough medical and ocular history, as well as imaging studies (especially CT or MRI) are prudent steps in the workup of suspected orbital RMS. CT imaging usually reveals a well-circumscribed, homogenous, round to ovoid mass which is isodense to muscle . Similarly, on T-1 weighted MRI imaging, an orbital RMS will usually appear as a round or ovoid mass which is isointense compared to extraocular muscles and hypointense with respect to orbital fat. On T-2 weighted images the mass appears hyperintense to both extraocular muscles and orbital fat. Orbital RMS generally enhances markedly with gadolinium contrast. If orbital RMS is suspected on the basis of clinical and radiologic findings, prompt biopsy of the lesion should be performed. Histopathology, immunohistochemistry, and electron microscopy establish a definitive diagnosis of RMS. Tissue samples should be obtained by excisional biopsy or incisional biopsy with fine needle aspiration biopsy (FNAB) occasionally being performed.
There have been significant improvements in the early diagnosis and management of orbital RMS over the past 30 years. As recently as the early 1970s, the mortality rate associated with orbital RMS was 70%. Up until the 1960s, the treatment of choice for this condition was orbital exenteration. Nowadays, orbital RMS requires some combination of surgery, irradiation, and chemotherapy, depending on the intergroup rhabdomyosarcoma study group (ISRG) stage, with orbital exenteration being reserved for very severe cases. For these reasons, it is important that the pediatric oncologist becomes involved as early as possible. For embryonal RMS, the 5-year survival is as high as 94% with modern therapy . Factors endowing patients with a more favorable prognosis include embryonal RMS, more favorable anatomic location, earlier stage, and patient age. Close follow-up is important to monitor for disease recurrence.
- Karcioglu Z, Hadjistilianou D, Rozans M, et al. Orbital Rhabdomyosarcoma. Cancer Control2004;11:328-33.
- Kodet R, Newton WA Jr, Hamoudi AB, et al: Orbital rhabdomyosarcomas and related tumors in childhood: relation- ship of morphology to prognosis—an Intergroup Rhabdomyosarcoma study. Med Pediatric Oncol 29:51–60, 1997
- Shields J.A., Shields C.L. Rhabdomyosarcoma: review for the ophthalmologist. Surv Ophthalmol. 2003;48:39–57.
- Shields C, Shields J, Honavar S, et al. Clinical Spectrum of Primary Ophthalmic Rhabdomyosarcoma. Ophthalmology2001;108:2284-2292.
- Wharam M, Beltangady M, Hays D, et al. Localized orbital rhabdomyosarcoma. An interim report of the Intergroup Rhabdomyosarcoma Study Committee. Ophthalmology1987;94:251-4
Title: Ocular Adverse Effects of Systemic Medications: Aminoquinolines
Author: Benjamin West, 4th Year Medical Student, Loma Linda University School of Medicine
LOCATION: Med Student Outline > II. Anatomical Approach to Eye Disease > Ocular Adverse Effects of Systemic Medications > 4. Aminoquinolines
Photographer: James Gilman, CRA, FOPS
Aminoquinolines are a class of drug that includes chloroquine, primaquine and hydroxychloroquine. While chloroquine and primaquine are used primarily in the prophylaxis and treatment of malarial infections, hydroxychloroquine is more commonly prescribed for rheumatologic and dermatologic conditions. Aminoquinolines can have serious ocular side effects, and referral to an ophthalmologist for close clinical follow up is recommended for all patients initiating long term therapy.
The most common and serious side effect of chronic aminoquinoline use is damage to the central part of the retina. The aminoquinoline binds to melanin in the retinal pigment epithelium and causes direct toxicity to the surrounding cells. On examination this presents as a spectrum of findings that depend on the degree of drug accumulation. Early disease causes a premaculopathy characterized by decreased foveal light reflex and retinal pigment stippling, but with no visual changes. More advanced disease shows the characteristic alternating rings of retinal hyperpigmentation and hypopigmentation surrounding the fovea that give this condition a “bull’s eye” appearance. These later macular changes are accompanied by irreversible vision loss.
Another side effect that has been associated with aminoquinoline use is a type of corneal change called vortex keratopathy (cornea verticillata). The drug deposits in the epithelial layer of the cornea and presents as a whorled or linear opacity. These changes can cause the patient to see halos around lights, but are reversible with discontinuation of therapy.
Two other rare ocular side effects of aminoquinolines include ciliary body dysfunction, presenting with impaired ability to focus on objects, as well as visually insignificant cataracts caused by drug accumulation in the cortex of the lens.
The greatest risks for toxicity include increased dose, older age, renal or hepatic dysfunction and obesity. Upon initiation of aminoquinoline therapy patients should undergo a baseline eye exam including visual acuity testing, visual field testing, slit lamp examination, indirect ophthalmoscopy and at least one specialized objective test such as fundus autoflourescence, optical coherence tomography or a multifocal electroretinogram. After 5 years of exposure patients should then receive annual eye exams. In patients who develop toxicity, drug therapy should be discontinued in order to prevent progression of retinopathy.
Slit lamp photo of cornea verticillata
- Yam J, Kwok A. Ocular toxicity of hydroxychloroquine. Hong Kong Medical Journal. 2006 Aug;12(4):294-304.
- Hansen M, Schuman S. Hydroxychloroquine-induced retinal toxicity. AAO.org, June 2011; Available from https://www.aao.org/eyenet/article/hydroxychloroquine-induced-retinal-toxicity
- Bowling, Brad. Kanski’s Clinical Ophthalmology. New York, NY: Elsevier Inc., 2016. Print.
- Marmor M, Kellner U, Lai T, Melles R, Mieler W. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology, 2016 Jun;123(6):1386-94.
Title: Amaurosis Fugax
Author: Alexzandra Douglass, MSII, University of Utah School of Medicine
Amaurosis fugax (AF), stemming from Greek amaurosis meaning dark and latin fugax meaning fleeting, refers to the transient loss of vision in one or both eyes.1,2 AF is defined as a sudden, transient visual loss or transient blurring or obscuration of vision with normal recovery after the episode. AF is considered a transient ischemic attack (TIA) and must be considered an ophthalmologic emergency.1–5
Patients typically present to the physician after the episode has resolved, in which case ophthalmologic and neurologic exams are normal. Reliance is then placed on the patient’s description of the transient visual loss (TVL). Important distinctions include monocular or binocular localization, onset, duration, description of the visual symptoms, associated features, and precipitating factors.1–5 Relevant medical and family history may also provide essential information for the diagnosis.
AF can cause monocular or binocular TVL. Generally, monocular lesions localize anterior to the optic chiasm, affecting the optic nerve or structures within the eye. Binocular lesions suggest a more posterior process, localizing to the optic chiasm, optic tract, optic radiations or to visual cortex.2,4,5 The onset is typically sudden and painless and lasts 1-15 minutes. 1–5 Painful vision loss suggests a different entity than AF. TVL from any etiology can be described as mild blurring to complete blackness, which involves part or all of the visual field. One specific description to note is the “altitudinal” pattern, resembling a curtain or shade ascending or descending over the patient’s visual field. This type of TVL is considered to be strongly suggestive of a vascular etiology.1–3
TVL, whether monocular or binocular, represents a heterogeneous group of disorders ranging from benign conditions to those with serious ophthalmologic and neurologic sequelae. Giant cell arteritis and severe carotid stenosis are among two of the disorders with grave consequences and should not be missed. A few of the most common underlying conditions are described below:
- Carotid artery disease: consider in a patient with vascular risk factors that describes an abrupt onset of monocular altitudinal TVL that affects the entire visual field of one eye. This type of TVL is most commonly due to small emboli from a severely stenosed (greater than 70%) ipsilateral internal carotid artery. Emboli from any vascular origin can cause transient impaction of any vessel in the ophthalmic circulation.2,3,5
- Giant cell arteritis: consider in an elderly patient that presents with accompanying symptoms of jaw claudication, scalp tenderness, headache and muscle weakness. TVL is not a common presentation of giant cell arteritis; however, when present is a grave prognostic factor.
- Ocular Migraine or Migraine with Aura: should be considered in patients of any age describing monocular or binocular TVL with or without positive visual symptoms that last for a relatively longer duration of time, such as greater than 20 minutes.2–4
- Retinal vasospasm and/or retinal migraine: consider retinal vasospasm in a young patient with positive visual symptoms such as scintillation, that have several episodes in one day.1,2
- Optic neuritis (multiple sclerosis): suspect this in patients describing transient loss of vision or blurring of vision associated with elevated body temperature after a hot shower or exercise (Uhthoff’s symptom). Uhthoff’s symptom is classically associated with multiple sclerosis and should prompt a corresponding workup, including an MRI of the brain with and without contrast.1,2 Optic neuritis also is typically accompanied by pain with eye movements.
- Papilledema: TVL is a relatively uncommon presenting symptom of papilledema and is suspected to be due to fluctuations of optic nerve head perfusion associated with changes in position or posture; thus a detailed funduscopic exam is critical. Papilledema can cause monocular or binocular TVL.1–3
- Cardiogenic embolism: emboli from the heart may lodge in the ophthalmic circulation and cause TVL; however, is more likely to cause a cerebral TIA.2,3
- Vertebro-basilar ischemia: consider in patients experiencing homonymous TVL. The vision loss may be isolated or accompanied by brainstem symptoms such as dysarthria, dysphagia, diplopia or cerebral symptoms such as hemiparesis, hemi-sensory loss or aphasia.2,3,5 This can cause monocular or binocular TVL.
Diagnostic workup should be tailored to the most likely underlying condition based on the patient’s age, pertinent medical history, description of the TVL and the physical examination. To minimize the possibility of missing potential diagnoses with serious sequelae, certain diagnostic procedures should be performed on most patients over 50 years old with vascular risk factors. These procedures include a careful dilated eye exam, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to rule out giant cell arteritis and carotid imaging to assess for carotid artery disease.1,2,4,5 The diagnostic workup can be more selective in young patients without vascular risk factors with a normal physical and ophthalmologic examinations or symptoms of migraine. However, the more that symptoms deviate from classic migraine, the broader the workup should become. 1,2,4,5 Below is an outline of indication for each diagnostic test:
- Ophthalmologic evaluation: all patients should receive a detailed, dilated eye exam.
- ESR and CRP: should be performed on all patients older than 50 years old and any time giant cell arteritis is suspected.
- Carotid imaging: should be performed on all patients older than 50 years old and younger patients with vascular risk factors.
- Cardiac evaluation: baseline ECG should consider in patients older than 50 years old if giant cell arteritis and carotid artery disease have been excluded.
- Brain MRI: Diffusion-weighted imaging (DWI) should be consider in patients over 50 years old with binocular symptoms to rule out vertebro-basilar ischemia or if multiple sclerosis is the suspected underlying etiology.
- Hypercoagulable testing: should be performed in patients with personal or family histories suggestive of hypercoagulable disorders and an otherwise negative workup.
Treatment for TVL is determined by the underlying cause. Two notable diagnoses to discuss include critical carotid artery stenosis (greater than 70%) and giant cell arteritis. Investigators recommend carotid endarterectomy (CEA) be performed on patients with internal carotid artery stenosis greater than 70%.2,3,5 Referral to neurosurgery or vascular surgery would be indicated at this time. If an elderly patient presents with jaw claudication, TVL and temporal tenderness and giant cell arteritis is suspected, start high dose corticosteroid therapy immediately, do not await inflammatory marker results. Patients with giant cell arteritis are at high risk of permanent vision loss and thus time to corticosteroid treatment should be minimized.2,3,5 These patients are then scheduled for an outpatient temporal artery biopsy to confirm the diagnosis.
- Lavalle PC, Cabrejo L, Labreuche J, et al. Spectrum of transient visual symptoms in a transient ischemic attack cohort. Stroke. 2013;44(12):3312-3317.
- Petzold A, Islam N, Hu HH, Plant GT. Embolic and Nonembolic Transient Monocular Visual Field Loss: A Clinicopathologic Review. Surv Ophthalmol. 2013;58(1):42-62.
- Hayreh SS, Bridget Zimmerman M. Amaurosis fugax in ocular vascular occlusive disorders: Prevalence and pathogeneses. Retina. 2014;34(1):115-122.
- Petzold A, Islam N, Plant GT. Patterns of non-embolic transient monocular visual field loss. J Neurol. 2013;260(7):1889-1900.
- Kvickström P, Lindblom B, Bergström G, Zetterberg M. Amaurosis fugax: Risk factors and prevalence of significant carotid stenosis. Clin Ophthalmol. 2016;10:2165-2170.
Author: Xavier Mortensen, MSIII, University of Utah School of Medicine
The image above demonstrates the course of visual information arriving from the right and left visual fields as they travel back to the occipital cortex. The light from the left visual field crosses and inverts through the lens and is detected by the right half of each retina. Likewise, light from the right visual field crosses and inverts through the lens and is detected by the left half of each retina. In other words, the image that projects onto our retina is upside down and backwards from what we are actually seeing.
The neuronal axons from the temporal half of the retina travel through the optic nerve to the optic chiasm but do not cross the chiasm and remain ipsilateral through the optic tract and to the occipital cortex. The neuronal axons from the nasal retina travel to the optic chiasm and cross to join the temporal fibers from the opposite eye. Thus, the right optic tract is composed of the left half of the visual field from each eye, or the nasal fibers from the left eye and the temporal fibers from the right eye. These fibers synapse at the lateral geniculate nucleus and in the Edinger-Westphal nucleus for the pupillary reflex. From there, the upper visual field information courses through the temporal lobe (Meyer’s loop) and the lower visual field travels through the parietal lobe. These optic projections finally synapse in the visual cortex within the occipital lobe where the visual information processed by the brain.
Below is an explanation of each of the visual field deficits depicted in the image above.
- Right Monocular Blindness: This occurs when the lesion is anterior to or in front of the optic chiasm. This has a broad differential, including everything from corneal disease or cataract to optic neuritis. If the location of the insult is the optic nerve, these patients typically will have a relative afferent pupillary defect.
- Bitemporal Homonymous Hemianopia: This occurs when the lesion is at the optic chiasm, compressing the decussating fibers. It is most often caused by abnormal growth of the pituitary gland, which lies just inferior to the optic chiasm. The nerve fibers that receive input from the nasal retina (temporal vision) are the only fibers that cross to the other side of the brain, resulting in loss of vision to the temporal visual fields only. In addition to bitemporal visual loss, patients often present with hormonal changes associated with a functioning pituitary adenoma due to an increased production of any of the following hormones: LH, FSH, TSH, ACTH, GH, prolactin, vasopressin, oxytocin, and alpha-MSH.
- Left Homonymous Hemianopia: This results from lesions to the optic tract in route towards the lateral geniculate body of the thalamus (location 3) as well as lesions right after the radiating fibers leave the lateral geniculate body (location 5). These lesions are often caused by strokes or neoplasms. Because the descending corticospinal motor tracts are nearby, they are often involved as well, which results in contralateral hemiparesis as an associated finding with homonymous hemianopia.
- Left Superior Homonymous Quadrantanopia: This visual defect is often referred to as pie in the sky. This visual defect happens when the inferior optic radiating fibers (Meyer’s loop) are damaged in the temporal lobe of the brain. Strokes involving the middle cerebral artery (MCA) can result in this presentation. Lesions to the temporal lobe produce other neurologic manifestations including aphasia, memory deficits (if dominant hemisphere), seizures, and auditory and visual hallucinations.
- Left Homonymous Hemianopia: See explanation of number 3 above.
- Left Inferior Homonymous Hemianopia: Damage to the more superior fibers of the optic radiations in the parietal lobe result in this visual defect. Since the parietal lobe is the principal sensory area of the cerebral cortex, these lesions often produce sensory deficits. Gerstmann’s syndrome (finger agnosia, agraphia, acalculia, and right-left disorientation) may accompany this visual defect if the dominant angular gyrus lobe is involved. Contralateral hemineglect is also seen in parietal lobe lesions of the non-dominant hemisphere, which can be difficult to distinguish from this visual field defect.
- Left Homonymous Hemianopia with Macular Sparing: Lesions of the occipital lobe will often result in this visual defect. The maculae are the central portion of the retina and are responsible for central high-resolution color vision. The very tips of the occipital cortices are where input of macular vision is received. This area has dual blood supply by both the MCA and posterior cerebral artery (PCA) and thus forms a watershed zone, protecting macular vision when only one of the major cerebral vessel distributions is affected.
- Biousse, Valerie, Sachin Kedar and Nancy Newman. UpToDate: Homonymous hemianopia. 21 June 2017. 27 January 2018. <https://www.uptodate.com/contents/homonymous-hemianopia#H18>.
- Brown, Thomas A and Sonali J Shah. USMLE Step 1 Secrets. 3rd Edition. Philadelphia: Elsevier Inc., 2013.
- Levin LA. Topical diagnosis of chiasmal and retrochiasmal disorders. In: Walsh and Hoyt Clinical
- Neuro-ophthalmology, 6th, Miller NR, Newman NJ, Biousse V, Kerrison JB (Eds), Williams
- & Wilkins, Baltimore 2005. p.503.
- Trobe JD. Visual fields. In: The Neurology of Vision, Trobe JD (Ed), Oxford, Oxford 2001. p.109.
- Liu GT, Volpe NJ, Galetta SL. Retrochiasmal disorders. In: Neuro-ophthalmology: Diagnosis and
- Management, Liu GT, Volpe NJ, Galetta SL (Eds), W.B. Saunders, Philadelphia 2001. p.296.
Title: Ocular Side-Effects of Corticosteroids
Author(s): Sahil Aggarwal, MS4, University of California, Irvine School of Medicine; Brian Ta, MS4, University of Utah School of Medicine
Photographer: James Gilman, CRA, FOPS, Moran Eye Center Date: 07/2018
CORE Category: Medical Student Education Outline > II. Anatomical Approach to Eye Disease > Ocular Adverse Effects of Systemic Medications > 1. Oral/topical/injected/inhaled Steroids
From local skin reactions to systemic autoimmune disorders, corticosteroids are an essential treatment modality for a wide spectrum of disease processes. However, as efficacious as they are therapeutically, they are heavily polluted with side effects. Patients chronically taking steroids often exhibit signs of metabolic syndrome, with elevated blood sugar, hypertension, and rapid weight gain. Additional adverse effects include easy bruising, osteoporosis, and emotional disturbances.1
In ophthalmology, steroids are predominantly used for treating inflammatory, autoimmune, and infectious diseases. They are often the first-line therapy in otherwise blinding conditions such as uveitis (inflammation of the uvea, or the pigmented layer of the eye including the iris, ciliary body and choroid) and giant cell arteritis.
There are several ocular side effects that are important to consider when prescribing steroids.2 It is important to note that all methods of steroid administration, including oral, topical, and inhalation, increase the risk for ocular side effects.3 Because of these risks, steroids must be used with caution and only when necessary.
MECHANISM OF ACTION
Corticosteroids exert their efficacy by altering the way genes are expressed throughout the body. In particular, gene products that are involved in inflammatory pathways are down-regulated, reducing the activity of inflammatory cells.4 Specific cascades affected by steroids include cytokine production and the arachidonic acid pathway, reducing the body’s ability to regulate inflammation.4 While inhibition of inflammatory cascades is vital to steroids’ treatment efficacy, the down-regulation of the immune system can lead to increased risk of infection.
OCULAR SIDE EFFECTS
There are four important ocular side effects of corticosteroids: steroid-induced glaucoma, cataract formation, delayed wound healing, and increased susceptibility to infection.
Glaucoma is a condition in which there is damage to the optic nerve, often related to elevated intraocular pressure (IOP). The result of this damage is a progressive, permanent vision loss. Steroid use can cause an increase in IOP by increasing the expression of ocular extracellular matrix proteins, thus increasing resistance to the outflow of aqueous from the eye.5 The risk of steroid-induced glaucoma depends on the duration of use and potency of the steroids themselves as well as the individual’s baseline risk for glaucoma.6-8 The risks factors that have been identified to place someone at risk for a steroid-induced increase in IOP include: pre-existing primary open angle glaucoma, a history of increased IOP with previous steroid administration, a diagnosis of Type 1 diabetes, or those who are very young or very old.9 Patients who are taking steroids long-term should be regularly evaluated by ophthalmology for IOP changes, and consideration for non-steroid medications should always be made.
Cataracts are a common finding in aging adults and are safely removed and replaced with an artificial lens during cataract surgery. Long-term steroid use is associated with an accelerated development of cataracts. While the mechanism of cataract development in this setting is not well understood, it is thought to involve steroid-induced changes in gene transcription within lens epithelial cells.10 Classically, the type of cataract associated with steroid use is called a posterior subcapsular cataract, which forms in the back of the lens (Figure 1).11 Patients on steroids who are experiencing reduced vision should be evaluated by an ophthalmologist.
Delayed Wound Healing and Risk of Infection
Steroids are often used in conjunction with topical antibiotics in ocular infections such as corneal ulcers. However, previous research has identified that steroids inhibit growth factors critical in wound healing.12 Similarly, without co-treatment with antibiotics, local ocular infections that are treated with steroids may become worse, especially viral infections such as herpetic keratitis.12 While local steroid therapy is valuable in infections of the eye, owing to their ability to reduce inflammation and scarring, these benefits must be weighed against the risk of recurrent infection and poor wound healing and require the close monitoring of an eye specialist.
Corticosteroids are vitally important in treating several systemic and local inflammatory or autoimmune conditions. While therapy is associated with side effects, including steroid-induced glaucoma, cataracts, poor wound healing, and progressing infections, these effects can be mitigated with attentive monitoring.13 Non-ophthalmologists should strongly consider referring any patient on prolonged systemic steroids to an eye-care specialist for monitoring for glaucoma and cataracts. The decision to prescribe topical steroids can be complex and should involve an ophthalmologist.
1. Buchman AL. Side effects of corticosteroid therapy. J Clin Gastroenterol 2001;33:289–94.
2. Renfro L, Snow JS. Ocular effects of topical and systemic steroids. Dermatol Clin
3. Daniel BS, Orchard D. Ocular side-effects of topical corticosteroids: what a dermatologist
needs to know. Australas J Dermatol 2015;56:164–9.
4. Comstock TL, DeCory HH. Advances in Corticosteroid Therapy for Ocular Inflammation:
Loteprednol Etabonate. Int J Inflam 2012;2012.
5. Phulke S, Kaushik S, Kaur S, et al. Steroid-induced Glaucoma: An Avoidable Irreversible
Blindness. J Curr Glaucoma Pract 2017;11:67–72.
6. Francois J. Cortisone et tension oculaire. Ann D’Oculist 1954; 187: 805.
7. Cantrill HL, Palmberg, Zink HA, Waltman SR, Podos SM, Becker B. Comparison of in
vitro potency of corticosteroids with ability to raise intraocular pressure. Am J
Ophthalmol 1975; 79: 1012–1017.
8. Francois J. Corticosteroid glaucoma. Ann Ophthalmol 1977; 9: 1075–1080.
9. Goñi FJ, Stalmans I, Denis P, et al. Elevated Intraocular Pressure After Intravitreal Steroid
Injection in Diabetic Macular Edema: Monitoring and Management. Ophthalmol Ther
10. James ER. The etiology of steroid cataract. J Ocul Pharmacol Ther 2007;23:403–20.
11. Moran CORE | Cataracts. http://morancore.utah.edu/medical-student-education-
outline/cataracts/ (accessed 28 Jul 2018).
12. Srinivasan M, Mascarenhas J, Rajaraman R, et al. The Steroids for Corneal Ulcers Trial.
Arch Ophthalmol 2012;130.
13. Abelson MB, Butrus S. Corticosteroids in ophthalmic practice. Chapter 23. In: Albert DM et
al., eds. Albert & Jakobiec’s Principles and Practice of Ophthalmology, 3rd ed.
Philadelphia: Saunders Elsevier; 2008.
Author: Nicholas Henrie, 1st Year Medical Student, University of Utah School of Medicine
Figure 1. Bottom: Labeled diagram of the eye. The anterior part of the eye is highlighted in the top left and top right. Top-Right: In healthy patients, the ciliary processes of the ciliary body secrete the aqueous humor into the posterior chamber. The fluid then flows up through the pupil into the anterior chamber maintaining pressure in both chambers. The fluid drains out of the anterior chamber through trabecular meshwork and into the canal of Schlemm.
Top-Left: Ciliochoroidal effusion alters this pathway through a series of steps: 1. Ciliary body edema occurs (caused by topiramate) 2. The lens thickens due to zonular fiber relaxation, inducing a myopic shift 3. The ciliary sulcus narrows 4. The iris and lens-iris diaphragm is anteriorly displaced 5. The forward displacement of the iris narrows the angle, blocking drainage of the aqueous humor. Blocked drainage leads to increased pressure and eventually acute angle closure glaucoma.2
Topiramate is an anticonvulsant drug that has FDA approval for the treatment of epilepsy and migraine headaches. Off-label uses include treatment of antipsychotic induced weight gain, bulimia nervosa, essential tremor, and alcohol dependence. Topiramate is available as a generic medication and is available as Qudexy XR, Topamax, Topamax Sprinkle, Topiragen and Trokendi XR.
Topiramate is a sulfamate derivative3 originally derived as an analog of fructose-1,6-diphosphate. As such, when taken orally topiramate is rapidly absorbed. Physiologically, topiramate affects sodium ion channels, GABA receptors, AMPA/kainate receptors, high voltage-activated calcium ion channels, and carbonic anhydrase isozymes.
Mechanism of Toxicity:
Topiramate’s ocular side effects include myopic shift, increased central cornea thickness, and most notably vision loss due to acute angle closure glaucoma. The mechanism of topiramate’s toxicity is induced edema of the ciliary body which in turn causes the ciliary processes to rotate anteriorly. 1,2,4 The ciliary body edema leads to relaxation of the zonular fibers and subsequent thickening of the lens, resulting in a myopic shift in vision (making the patient more near-sighted). The ciliary sulcus narrows, contributing to the forward displacement of the iris. The lens-iris diaphragm is anteriorly displaced, leading to a peripheral shallowing of the anterior chamber where the iris moves closer to the cornea and blocks the angle of the eye (see diagram). This can block the trabecular meshwork and canal of Schlemm, preventing drainage of the aqueous humor. Blocked aqueous humor drainage combined with the thickening of the lens leads to acute angle closure glaucoma or crisis.
Simultaneous bilateral acute angle closure glaucoma—especially with a myopic shift—warrants a careful medication review for the recent or semi-recent initiation of topiramate. It is also worth reviewing the past medical history for conditions that would be treated by topiramate.1
Treatment of topiramate2 induced angle closure glaucoma involves, most importantly, cessation of the topiramate. In addition to stopping the medication, starting a cycloplegic eye drop such as atropine or cyclopentolate will dilate the pupil and stimulate posteriorization of the lens-iris diaphragm. Depending on the degree of resultant inflammation, topical steroids can be added. Refracting the patient helps identify the myopic shift which aids in making the diagnosis but the refractive change is reversible so there is no utility in prescribing new glasses.
- Hesami O., Simindokht Hosseini S., Kazemi N, Hosseini-Zijoud SM., Moghaddam NB., Assarzadegan F., et al. Evaluation of Ocular Side Effects in the Patients on Topiramate Therapy for Control of Migrainous Headache. Journal of Clinical and Diagnostic Research, 2016; 10(3); NC01
- Aminlari A, East M, Wei W, Quillen D. Topiramate Induced Acute Angle Closure Glaucoma. Open Ophthalmol J. 2008; 2: 46–47.
- Ah-kee Elliott Yann, Egong, E., Shafi, A., Lim, L. T., & Yim, J. L. (2015). A review of drug-induced acute angle closure glaucoma for non-ophthalmologists. Qatar Medical Journal, 2015(1), 6.
- Ikeda N, Ikeda T, Nagata M, Mimura O. Ciliochoroidal Effusion Syndrome Induced by Sulfa Derivatives. Arch Ophthalmol. 2002;120(12):1775.
Title: Acute Angle Closure Glaucoma
Author (s): Troy Teeples, 4th year medical student, University of Utah School of Medicine; Griffin Jardine, MD
Image Designer: Troy Teeples, MSIV University of Utah School of Medicine
Keywords/Main Subjects: Acute Angle Closure Glaucoma, painful eye, red eye, pupillary block, halos
Acute Angle Closure Glaucoma
What is it?
Angle-closure glaucoma is a group of diseases in which the angle of the anterior-chamber (the fluid-filled space between the iris and the cornea) closes, which can occur both acutely and chronically. Acute angle-closure glaucoma (AACG) is an ophthalmologic emergency where the intraocular pressure (IOP) rises rapidly due to a sudden blockage of the trabecular meshwork, which normally functions to drain the aqueous humor of the eye. AACG can subsequently be divided into pupillary block versus non-pupillary block. Pupillary block is where a mid-dilated iris in an already crowded eye makes contact with the lens in a way that impedes aqueous flow through the pupil. This causes a pressure buildup behind the iris, shifting it anteriorly which further closes the angle and creating a closed fluid system with no outflow, thus rapidly increasing IOP.
Chronic angle closure can cause permanent vision loss over time due to a chronically elevated IOP but typically does not cause pain because of the eye’s ability to adapt to the gradual change in IOP over time.
In AACG, patients present with severe eye pain, redness, nausea, vomiting, blurred vision, headache, and may complain of seeing halos around lights. Risk factors for AACG include age (older than 50), being Asian, female or far-sighted (hyperopic). The crisis can be triggered by events that cause pupillary dilation, such as darkened movie theaters, stress or certain medications/drugs. Examination will reveal an elevated IOP, a reddened eye with a steamy cornea (corneal edema) and a moderately dilated pupil that is not reactive to light. Again, a slow, steady rise in IOP over weeks to months—such as in chronic angle closure—is painless and asymptomatic until either detected by a clinician or the patient has substantial and often irreversible optic nerve damage and vision loss.
AACG warrants an emergent ophthalmology consult. Untreated patients can develop permanent vision loss within hours of symptom onset. Initial treatment is targeted to relieve the acute symptoms and reduce the IOP, which is primarily done by drops and oral medicine. Medical therapy works via suppression of aqueous humor production and includes:
- Oral or topical carbonic anhydrase inhibitors (acetazolamide, dorzolamide)
- Topical beta-blockers (timolol)
- Topical alpha-2 adrenergic agonists (brimonidine)
Once the pressure is stabilized, surgical intervention can be employed to reduce the risk of future events, such as a laser peripheral iridotomy (LPI). LPI is the more definitive treatment of primary AACG and should be performed 24-48 hours following resolution of an acute attack in order to prevent future attacks. LPI corrects a pupillary block by using a laser to create an opening in the iris, thereby allowing aqueous fluid to bypass the pupil.
Khazaeni B, Khazaeni L. Glaucoma, Acute Closed Angle. [Updated 2017 Apr 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430857/. Accessed 5/18/2018.
Weinreb RN, Aung T., Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311:1901–1911.
Faculty Approval by: Griffin Jardine, MD
Copyright statement: Copyright Author Name, ©2018. For further information regarding the rights to this collection, please visit: http://morancore.utah.edu/terms-of-use/