A Case of Bilateral Internuclear Ophthalmoplegia (INO)

 

Resident Pearl by Dr. Saly Halawa 

iFMEM PGY2

Dalhousie University

Reviewed by Dr. B Ramrattan

Copy Edited by Dr. J Vonkeman

Pdf Download: EMSJ Bilateral INO SHalawa

 


Case Presentation

A 42yo male presents to the Emergency Department with abrupt onset right-sided facial numbness and double vision. His facial numbness quickly improved but he continued to have diplopia and gait ataxia. He denied headache, nausea or photophonophobia. The patient had a history of sickle cell disease and diabetes. His medications included hydroxyurea and insulin. On physical examination, he was unable to adduct his eyes bilaterally on lateral gaze with abducting nystagmus. His power, tone, reflex, and sensation were all normal.


Internuclear Ophthalmoplegia (INO)

Internuclear ophthalmoplegia (INO) is a neurologic condition characterized by impaired control of conjugate eye movements (1). It is caused by a lesion of the medial longitudinal fasciculus (MLF) in the brainstem. The MLF is the pathway containing internuclear neurons connecting cranial nerve nuclei that control conjugate eye movements. These include the nucleus of the abducens nerve (CN VI) in the pons and the contralateral nucleus of the oculomotor nerve (CN III) in the midbrain supplying the medial rectus (1). Together CNIII and CN VI allow for adduction and abduction of the eye, respectively. For instance, interneurons of CNVI on one side project across the midline to the contralateral MLF which ascends to CNIII to control the medial rectus on that side, allowing the lateral and medial rectus to move the eyes together (1). In this way, the MLF coordinates eye movements between both eyes allowing for conjugate gaze. Patients with INO have an adduction deficit on the ipsilateral side with associated contralateral nystagmus of the abducting eye.

INO is named with respect to the side of the adduction deficit, which is the side of the MLF lesion. A R sided INO is due to a lesion of the R MLF. Patients may also present with bilateral INO as in the case presented here.

 

Figure 1: Adduction Defects produced by Internuclear Ophthalmoplegia (1)

Patients with INO often experience horizontal diplopia due to dysconjugate gaze or they may report vertical-oblique diplopia due to associated skew deviation (1). Patients may also present with difficulty in tracking fast-moving objects as a result of a mismatch in saccadic movements between the eyes.


Differential

The differential diagnosis for INO is broad (1). The most common causes of bilateral INO include multiple sclerosis in younger patients, often younger than 50 yrs old, or due to brainstem infarction in older patients. Other causes of INO include infection, toxicity to medications including amitriptyline, benzodiazepines or ethanol, chiari malformations or trauma. In the present case, bilateral INO was the first presentation of MS due to demyelination of the MLF.


Prognosis

Prognostically, INO symptoms do improve over time, often resolving spontaneously after an average of 2 months, but up to 12 months (2). Associated neurologic symptoms such as vertigo, ataxia, sensory or speech deficits are poor prognosticating factors. Those with cerebrovascular etiology have less favorable recovery as well.

Figure 2: Internuclear Ophthalmoplegia caused by lesion at the Medial Longitudinal Fasciculus (4)

Video link: https://www.youtube.com/watch?v=eL3_6yYJdUA&ab_channel=MoranCORE

 


Case Conclusion

CT angiography of the brain demonstrated no evidence of acute infarction. MRI showed periventricular white matter hyperintensities which was also seen in the corpus callosum, suspicious for multiple sclerosis. He was given a five-day trial of methylprednisolone.


Bottom Line

Though uncommon, internuclear ophthalmoplegia points to a brainstem lesion with a wide variety of causes. Multiple sclerosis should be suspected in a young patient presenting with bilateral INO.


References

  1. Toral M, Haugsdal J, Wall M. Internuclear Ophthalmoplegia. EyeRounds.org. posted June 8, 2017; Available from: http://EyeRounds.org/cases/252-internuclear-ophthalmoplegia.htm
  2. Eggenberger E, et al. Prognosis of ischemic internuclear ophthalmoplegia. Ophthalmology. 2002; 109(9):1676-8.
  3.  https://www.youtube.com/watch?v=eL3_6yYJdUA&ab_channel=MoranCORE
  4. https://sketchymedicine.com/2013/12/internuclear-opthalmoplegia/

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Drop it like it’s Hot – Tetracaine eye drops following corneal abrasion?

Drop it like it’s Hot- A case presentation and critical appraisal on the use of tetracaine eye drops following corneal abrasion: A Medical Student Pearl

Claudia Cullinan

DMNB, Med 3

Reviewed by Dr. Kavish Chandra


Case:

It’s a sunny July afternoon and you are just starting your shift in the ED when a 25-year-old male presents with sudden onset of severe right eye pain. You bring him into the exam room, and he explains he ran into a tree branch. He is reluctant to open his eye due to the pain and his eye is watering uncontrollably. He also keeps his sunglasses on while you talk because his eye is now extremely sensitive to the bright ED lights.

The patient is visibly in a lot of distress, so you do a quick penlight exam and attempt to assess visual acuity to confirm there is no evidence of penetrating trauma.

At this point you suspect a corneal abrasion, so you move onto a slit lamp and fluorescein examination and add a tetracaine 0.5% (topical anesthetic) to the affected eye. The patient appears more comfortable within seconds. You are able to complete the exam with the patient sitting comfortably in the exam chair. There is no evidence of Seidel sign (streaming fluorescein caused by leaking aqueous humor) and no visible foreign body in the eye. You can visualise a linear yellow lesion along the lateral cornea when viewed with fluorescein under cobalt blue light and you are confident this is a simple corneal abrasion.


Figure 1. Corneal abrasion viewed with cobalt blue light after fluorescein staining. Accessed from DFOptometrists.com


You explain to the patient that he has a corneal abrasion, prescribe him erythromycin 0.5% ophthalmic ointment to be inserted into the affected eye QID for 5 days and encourage him to avoid rubbing his eyes. He can also take PRN ibuprofen if needed. He asks “That one eye drop made my eye feel so much better, can I have a bottle of that to bring home?”

You know he is talking about Tetracaine, and you remember learning about the controversy of using topical anesthetics for the outpatient treatment of corneal abrasions….what do you tell him?


Critical Appraisal : Short-term topical tetracaine is highly efficacious for the treatment of pain caused by corneal abrasions: a double-blind, randomized clinical trial. (2020)

Background:

Corneal abrasions are among the most common ophthalmic presentations to the emergency department (ED). They occur when the corneal epithermal becomes disrupted, such as when tiny foreign bodies land in your eye or when your new puppy accidentally scratches the surface of your eye.  Although corneal abrasions typically heal rapidly with minimal risk of complication, they are often VERY painful and can be extremely debilitating. There has been controversy on whether patients should be discharged home with topical anesthetics for short term management of corneal abrasions because of previously described safety concerns regarding toxicity. However, recent literature is beginning to surface suggesting there may be a role for short term topical analgesia following simple corneal abrasion, with appropriate follow up.

Figure 2. Anatomy of the cornea. Accessed form AAFP.org

Clinical Question:

How effective is the home use of topical tetracaine every 30 minutes PRN pain for 24 hours following corneal abrasion?

Reference

Shipman, S., Painter, K., Keuchel, M., & Bogie, C. (2021). Short-Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial. Annals of Emergency Medicine, 77(3), 338–344.       https://doi.org/10.1016/j.annemergmed.2020.08.036


Study Overview:

Population: Patients 18-80 years old presenting to an urban ED in Oklahoma City with suspected acute corneal abrasion.

Intervention: 2mL bottle of Tetracaine 0.5% one drop applied q30 minutes PRN pain for a maximum of 24 hours + antibiotic ophthalmic solution (polymyxin B sulfate/ trimethoprim sulfate) 2 drops to affected eye q4h.

Control: 4 separate 0.5mL ampules of artificial tears (Systane) one drop applied q30 minutes PRN pain for a maximum of 24 hours + antibiotic ophthalmic solution (polymyxin B sulfate/ trimethoprim sulfate) 2 drops to affected eye q4h.

Outcome: Pain rating at 24-48h follow up.

Methods:

  • Prospective, double blind, randomised control trial of topical tetracaine vs control (artificial tears) in the ED following diagnosis of corneal abrasion in the ED.
  • Took place in an urban Oklahoma ED from 2015 to 2017.
  • One hundred and eleven patients were included and were randomly assigned to the treatment or control group.
  • The patients in both groups had similar baseline characteristics and baseline numeric rating scale (NRS) pain scores (0-10, 10 being the most pain).

Inclusion criteria:

Patients 18 to 80 years old, presenting to the ED with suspected acute corneal abrasion, and gave written informed consent.

Exclusion criteria:

Contact lens wearers, previous corneal surgery or transplant in the affected eye, presented more than 36 hours after their injury, had a grossly contaminated foreign body, had coexisting ocular infection, currently pregnant, retained foreign body, penetrating eye injury, receiving immunosuppression, allergy to study medication, unable to attend follow-up, unable to fluently read and speak English or Spanish, and any injury requiring urgent ophthalmologic evaluation.

Results:

Main outcomes at the 24-48hr follow up appointment:

  • The overall numeric rating scale (NRS) pain score was significantly lower in the tetracaine group compared to the control group (1 versus 8, P<0.001).
  • The number of patients found to have a small residual corneal abrasion on their follow up slit-lamp examination was similar between groups (18% in the tetracaine group and 11% in the control group).
  • There were only two complications in the tetracaine group (versus 6 in the control group), with similar rates of worsening corneal abrasions in both groups. All patients had normal healing after 10 days. No serious adverse outcomes were encountered.

Table 1. Patient baseline demographics and 24-48hr follow up data points.

Group Tetracaine (n=59) Control (n=59)
Age, y 35 (28-43) 38 (27-47)
Male patients, No. (%) 36 (61) 34 (58)
Baseline pain rating 7 (6-7.5) 7 (6-8)
24-48hr pain rating 1 (1-2) 8 (7-8)
No. of hydrocodone tablets recorded 1 7
Adverse Events, No (%) 2 (3.6) 6 (11)

Limitations and suggestions for future studies:

  • Although this was a double-blind study, there are two things that could have made patients aware of their treatment group. First, the control was packaged in 4 ampules and the treatment was packaged in a single bottle. Second, Tetracaine burns when administered to the eye and Systane (control) does not.
  • The study was slightly underpowered for the primary outcome of efficacy and certainly not powered to determine safety for rare adverse events associated with topical anesthetics. That being said, there are more patients in this trial demonstrating short term safety than previous care reports and series demonstrating tetracaine harm.
  • There was an extensive exclusion criterion, including patients who wear contacts (which are a common cause of corneal abrasions). By broadening the inclusion criteria, the results could be applied to a greater number of patients.
  • Patients were required to return for follow up at which time they were required to return their “study drops” so the drops cannot be abused. It would be more feasible to limit the amount of eye drops in the bottle so the patient does not have to return to the ED for bottle disposal.

Our conclusions:

Short term topical tetracaine is an efficacious analgesic for acute corneal abrasions, is associated with less hydrocodone use compared to control, and appears to be safe.

 


Case

Back to our original question…what do we tell our patient?

Provide him with a limited number of tetracaine drops and administer one drop in affected eye q30 minutes PRN pain for a maximum of 24 hours. Advise him to return to ED if his symptoms persist beyond 48 hours or get worse.


References

McGee, H. T., & Fraunfelder, F. (2007). Toxicities of topical ophthalmic anesthetics. Expert Opinion    on Drug Safety, 6(6), 637–640. https://doi.org/10.1517/14740338.6.6.637

Shipman, S., Painter, K., Keuchel, M., & Bogie, C. (2021). Short-Term Topical Tetracaine Is Highly        Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized             Clinical Trial. Annals of Emergency Medicine, 77(3), 338–344.       https://doi.org/10.1016/j.annemergmed.2020.08.036

Wipperman, J. L., & Dorsch, J. N. (2013). Evaluation and management of corneal abrasions.    American Family Physician, 87(2), 114–120.

Yu, C. W., Kirubarajan, A., Yau, M., Armstrong, D., & Johnson, D. E. (2021). Topical pain control for     corneal abrasions: A systematic review and meta-analysis. Academic Emergency Medicine, 28(8), 890–908. https://doi.org/10.1111/acem.14222

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A case of Herpetiform Keratitis- Clinical evaluation and important considerations.

A case of Herpetiform Keratitis- Clinical evaluation and important considerations: A Resident Clinical Pearl

Bonnie He, PGY1

Ophthalmology, Dalhousie University

Reviewed by: Dr. Cherie Adams

Copyedited by: Dr. Mandy Peach

Case

A 68-year-old female presented to SJRH Emergency Department with a three-day history of atraumatic worsening of right eye pain, photophobia, and decreased vision. She denied any experience of flashing lights or “curtain falling”. She reported a long-standing history of glaucoma for which she was previously prescribed brimonidine (alpha-agonist) ophthalmic drops and was prescribed travoprost (prostaglandin) ophthalmic drops approximately one week prior to presentation. Additional ophthalmologic history revealed used of glasses, but not contact lenses, and bilateral cataract surgery two years previously. Of particular note, she recounted an episode of “sores from her upper lip along the side of her nose to right lower eyelid” in the past for which she was treated with oral valacyclovir. Further history positive for hypertension, for which she is prescribed ramipril, and type 2 diabetes mellitus, for which is is prescribed metformin. She is a retired schoolteacher, non-smoker, social drinker and denies any recreational drug use.
Visual acuity from 20 feet with spectacle correction revealed was 20/100 on the right (OD) and 20/30+1 on the left (OS). Her intraocular pressures were OD 17 and OS 19. Examination revealed mild upper and lower eyelid edema and moderate conjunctival injection. Fluorescein staining of the right cornea revealed four small dendritic epithelial defects (Figure 1) at about the 6 o’clock position. External and slit lamp examination of the left eye was normal. Fundoscopic examination to check the optic disc, macula, retinal vessels, and periphery were deferred.

Figure 1A: 4 small dendritic epithelial lesions can be seen at the 6’oclock position.

 

Figure 1B: Classic dendritic corneal epithelial lesions 17.

OPHTHALMOLGIC ASSSESSMENT:

Ocular complaints are common in emergency care settings. Yet, the quantity and quality of ophthalmology education varies significantly across Canada, with both medical students and residents report receiving insufficient ophthalmic medical education from medical education curricula.1-3
Proper history and physical examination taking skills are crucial to the appropriate management of patients with a red eye. The American Academy of Ophthalmology recommends the 8-point physical exam as a systematic approach to any eye problems:

  1. Visual acuity
    • Position the patient 20ft or 6m away from the Snellen chart to test for distance vision
    • Document whether it is their best corrected visual acuity, (ie. did they have their glasses or contact lens on at the time of the exam)
  2. Pupils
    • In dim room light, check for:
      1. Direct response by looking for pupil constriction in the eye being shined
      2. Consensual response by looking for pupil constriction in the other eye (eye that is not being shined)
  • Rapid Afferent Pupillary Defect (RAPD) with the swinging light test by shining light back and front between eyes
  1. Extraocular motility and alignment
    • Conduct a “H test” to test for the 9 cardinal positions of gaze by tracing out the letter “H” in the air while monitor their eyes for 3 S’s: speed, smoothness, and symmetry
    • Ask patient to follow your finger with their eyes while keeping their head still in the center and note for any double vision at certain gazes
  2. Intraocular pressure
    • The Icare tonometer requires no local anesthetic
    • Insert probe into tonometer and anchor the tonometer to the seated patient’s eyebrow.
    • Slowly bring tonometer probe towards patient light until the light turns green – now you’re ready to press the button that will automatically measure the patient’s intraocular pressure
  3. Confrontation visual fields
    • At about 1 arm’s-length away, test each eye individually by holding up 1 or 2 fingers and ask patient how many fingers they see
    • Ask patient to close their OS and fixate on your nose. Close your OS to assess with your open OD.
    • To check OS, ask the patient to close their OD and fixate on your nose. Close your OD to assess with your open OS.
  4. External examination
    • Assess for any obvious globe rupture, ecchymoses, deformities or lesions around the eye
    • Check to see if there’s any ptosis (lid drooping)
  5. Slit lamp examination (watch this video to learn how to perform a slit lamp exam: https://www.youtube.com/watch?v=gHW5OYj1Gf8
    • Assess for the following structures
    • Lids/lashes/lacrimal system: edema, erythema, lesions
    • Conjunctiva/sclera: injection, subconjunctival hemorrhage
    • Cornea: foreign body, fluorescein stain + cobalt blue light to assess corneal integrity (ie. corneal abrasions, herpetic dendrites), Seidel test (leakage of aqueous humour)
    • Iris: round (normal) vs. peaked (abnormal)
    • Anterior chamber: any hyphema, hypopyon, cells, flare
    • Lens: opacity
  6. Fundoscopic examination
    • In the emergency department, fundoscopy is typically undertaken in the undilated eye.
    • May consider dilating the eye with tropicamide (dilating drop) to visualize the back of the eye with the slit lamp or direct ophthalmoscope
    • Assess for the following structures:
      1. Optic nerve: cup-to-disc ratio, pallor, symmetry between eyes
      2. Macula: foveal light reflex
  • Vessels: Arteriovenous (AV) nicking, silver or copper wiring,
  1. Periphery: bleeding

DISCUSSION:

Given the patient’s endorsed history suggestive of ipsilateral V2 herpes zoster and classic dendritic corneal lesions, the leading differential diagnosis for her acute on chronic ocular pain in this case would be zoster keratitis, though herpes keratitis should also be considered, particularly in patients with identified history and recent episode of orolabial cutaneous HSV. Interestingly, she was started on travoprost for her glaucoma a week prior to her presentation. Topical ocular hypotensive agents, including travoprost, are known to have a myriad local and systemic side effects including: superficial punctate keratitis, corneal erosion, bradycardia, hypotension, and bronchoconstriction, are common.4,5 However, of particular interest in this case,  multiple clinical and animal studies have reported that topical prostaglandins for ocular hypertension are culprits  associated with herpes simplex virus (HSV) keratitis or varicella-zoster virus (VZV) keratitis.6-13 It is thought that prostaglandin analogues such as travaprost may induce the reactivation of HSV keratitis by releasing endogenous prostaglandins in the iris and ciliary muscles.9,14-16 Therefore it could also be very well possible that she may have developed HSV keratitis.

 

Irrespective of which differential was truly causing this patient’s symptoms the antiviral treatment for zoster ophthalmicus and HSV keratitis are the same: valocylcovir 1g TID PO x 7 days (or acyclovir 800mg po five times daily if cost of valcyclovir is prohibitive) and arrangements were made for next-day ophthalmologist consultation.

 

BOTTOM LINE:

Always take a thorough ophthalmologic history for patients with ocular complaints, including complete medication history.

Always ask about contact lens use in a history in any patient with a painful red eye.

Always conduct a complete physical exam for patients with ophthalmologic complaints using the AAO 8-point framework described above.


REFERENCES

  1. Sim D, Hussain A, Tebbal A, Daly S, Pringle E, Ionides A. National survey of the management of eye emergencies in the accident and emergency departments by senior house officers: 10 years on—has anything changed? Emerg Med J. 2008;25(2):76-77. http://emj.bmj.com/content/25/2/76.abstract. doi:10.1136/emj.2007.049999.
  2. Noble J, Somal K, Gill HS, Lam W. An analysis of undergraduate ophthalmology training in Canada. Canadian Journal of Ophthalmology. 2009;44(5):513-518. http://www.sciencedirect.com/science/article/pii/S0008418209801130. doi:https://doi.org/10.3129/i09-127.
  3. Gostimir M, Sharma RA, Bhatti A. Status of Canadian undergraduate medical education in ophthalmology. Canadian Journal of Ophthalmology. 2018;53(5):474-479. http://www.sciencedirect.com.ezproxy.library.ubc.ca/science/article/pii/S0008418216309553. doi:https://doi-org.ezproxy.library.ubc.ca/10.1016/j.jcjo.2017.11.015.
  4. Inoue K. Managing adverse effects of glaucoma medications. Clinical ophthalmology (Auckland, N.Z.). 2014;8:903-913. https://pubmed.ncbi.nlm.nih.gov/24872675 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025938/. doi:10.2147/OPTH.S44708.
  5. Anwar Z, Wellik SR, Galor A. Glaucoma therapy and ocular surface disease: current literature and recommendations. Curr Opin Ophthalmol. 2013;24(2):136-143. doi:10.1097/ICU.0b013e32835c8aba [doi].
  6. Kroll DM, Schuman JS. Reactivation of herpes simplex virus keratitis after initiating bimatoprost treatment for glaucoma. Am J Ophthalmol. 2002;133(3):401-403. doi:S0002939401013605 [pii].
  7. Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes simplex keratitis. Am J Ophthalmol. 1999;127(5):602-604. doi:S0002939499000501 [pii].
  8. Alm A, Grierson I, Shields MB. Side effects associated with prostaglandin analog therapy. Surv Ophthalmol. 2008;53 Suppl1:93. doi:10.1016/j.survophthal.2008.08.004 [doi].
  9. Soomro MZ, Moin M, Attaulla I. Latanoprost and Herpetic Keratitis. Pakistan Journal of Ophthalmology. 2011;27(4).
  10. Kothari MT, Mehta BK, Asher NS, Kothari KJ. Recurrence of bilateral herpes simplex virus keratitis following bimatoprost use. Indian J Ophthalmol. 2006;54(1):47-48. doi:10.4103/0301-4738.21617 [doi].
  11. Ekatomatis P. Herpes simplex dendritic keratitis after treatment with latanoprost for primary open angle glaucoma. Br J Ophthalmol. 2001;85(8):1008-1009. doi:10.1136/bjo.85.8.1007a [doi].
  12. Morales J, Shihab ZM, Brown SM, Hodges MR. Herpes simplex virus dermatitis in patients using latanoprost. Am J Ophthalmol. 2001;132(1):114-116. doi:S0002939401010121 [pii].
  13. Villegas VM, Diaz L, Izquierdo NJ. Herpetic keratitis in a patient who used two different prostaglandin analogue ophthalmic solutions: a case report. P R Health Sci J. 2008;27:348+. https://link.gale.com/apps/doc/A189052227/HRCA?u=anon~6a050068&sid=googleScholar&xid=2c140d29.
  14. Dios Castro E, Maquet Dusart JA. Latanoprost-associated recurrent herpes simplex keratitis. Arch Soc Esp Oftalmol. 2000;75(11):775-778.
  15. Gordon YJ, Yates KA, Mah FS, Romanowski EG. The effects of Xalatan on the recovery of ocular herpes simplex virus type 1 (HSV-1) in the induced reactivation and spontaneous shedding rabbit models. J Ocul Pharmacol Ther. 2003;19(3):233-245. doi:10.1089/108076803321908356 [doi].
  16. Kaufman HE, Varnell ED, Toshida H, Kanai A, Thompson HW, Bazan NG. Effects of topical unoprostone and latanoprost on acute and recurrent herpetic keratitis in the rabbit. Am J Ophthalmol. 2001;131(5):643-646. doi:S0002939400009107 [pii].
  17. Yu, Hubert (2019) Canadiem Medical Concepts: Approach to Corneal Disorders in the ED

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