Marine Mammal Ophthalmology

Question 1

Describe the uniqe anatomy of the cetacean eye.

Do they have a nasolacrimal system?

Describe teh shape of the cornea?

How does the eye accomodate?

What does the retina look like?

Answer 1

Cetaceans

• Anatomy
  
  • Lack nasolacrimal system
  • Hemispherical globe (shorter in vertical axis)
  • Cornea
    
    • Thicker cornea at periphery, flattened
    • 5 layers to cornea: epithelium, Bowman’s layer, stroma, descemet’s membrane, endothelium
    • Bowman’s layer absent in pygmy sperm whale
    • Doesn’t contribute to refraction (lens does)
  • Emmetropic underwater (near and far)
  • Robust iris musculature, vestigial or lacking ciliary body musculature→ Little accommodative ability of lens
  • Hypothesis for accomodation: retrobulbar muscles pull globe in → inc IOP → lens moves forward
  • Retina
    
    • Holangiotic w/ sparse large ganglion cells; pigment only at periphery
    • Fibrous tapetum lucidum covering majority of fundus
  • Encapsulated sensory corpuscles in anterior uvea, sclera surrounding anterior uvea, trabecular meshwork, or combo of these

Question 2

Describe the unique physiology of the cetacean eye.

What are the tear layers in marine mammals? How does this compare to terrestrial mammals?

Which layer is the thickest and most important?

Answer 2

• Physiology
  
  • Precorneal tear film - lubricates, protects
    
    • Affected by health and environment
    • Terrestrial mammal tears have 3 layers: glycocalyx + mucus, aqueous, lipid
    • Cetaceans: mucus layer is most copious, aqueous second most copious, lack lipid component (no meibomian glands)
    • Most important layer: similar to glycocalyx, high viscosity, high carbohydrate
    • Mucus layer: resistance to infection
    • Conjunctival cells release GFs important in paracrine signaling
  • Harderian gland present in all species evaluated
  • Salinity of pool and temp of water account for significant tear pH variation

Question 3

Describe corneal disease in cetaceans.

Compare medial, axial, horizontal, and temporal keratopathies.

Which of these are the most common?

What are some common predisposing factors?

How do these animals present?

Answer 3

• Cornea
  
  • Most common structure affected
  • Medial keratopathy
    
    • Most common (50% of eyes and 54% of animals surveyed)
    • Usually bilateral
    • UV exposure, others
    • Gradually progressive, begins medial conjunctiva pigmentation → limbus → cornea
      
      • Vascularization and opacities, Edema, fibrosis
  • Axial keratopathy
    
    • Second most common corneal lesion
    • Water quality, UV, others
    • Begin as pinpoint opacity→ round, oval opacity to stromal depth
    • NOT clinically painful unless infected
  • Horizontal keratopathy
    
    • Third most common
    • Oxidative stressors (water quality, UV, oral fluoroquinolones, others)
    • Unilateral or bilateral
    • Transient initially, then permanent
    • Any age
    • Painful
    • Can have coppery green rust color
  • Temporal keratopathy
    
    • Less common than medial, but similar
    • UV not a factor (affects indoor and outdoor)
  • Predisposing factors? Water quality, inc UV index, → acute corneal edema or horizontal keratopathy
  • C/S: blepharospasm, blepharedema, worsening corneal edema, corneal ulceration, cellular infiltrates, abscess formation
  • Trauma, ulcers
    
    • Need aggressive treatment
    • Pseudomonas aeruginosa is most common organism to cause rapid stromal malacia

Question 4

Describe the treatment of corneal disease in cetaceans.

When the eye is closed what systemic antibiotics should be used?

Are ointments or drops preferrred? Why?

What ophthalmic antibiotics are preferred?

What immunomodulatory agents can be of use?

Answer 4

• Treatment:
  
  • Antimicrobials
    
    • Topical ointments not recommended due to thick tear film
    • Suspensions drops are preferred
    • 3% acetylcysteine prior to medication or mixed in appears to help the drug enter the tear film
    • Oral doxycycline and quinolone when severe blepharospasm is present
      
      • Extended fluoroquinolones can cause horizontal keratopathy and photophobia
        
        • Discontinue once the eye is open and topicals can be applied
      • Doxy promotes corneal wound healing, inhibits matrix metalloproteinase-9 and inflammation; supports ocular surface integrity; stabilizes stroma
    • Neomycin-polymyxin B - gramcidin generally will address the coliforms present
    • Tobramycin or gentamicin topical are good for pseudomonas, e. Coli, and kelbsiella
    • Ofloxacin commonly used, doesnt sting like cipro
    • Cytology and Culture important ;complicated by contamination
    • Topical antifungals: natamycin, vorizonazole (more cost effective; have to compound)
    • Oral antifungals: fluconazole, voriconazole, terbinafine
  • Immunomodulatory therapy
    
    • Calcineurin inhibitors, cyclosporine and tacrolimus
    • Cyclosporine: inhibits IL2 (halts T cell activation), enhances tear film production, increases goblet cell density
    • Tacrolimus: macrolide antibiotic; more potent than cyclosporine but similar MOA

Question 5

How prevalent are cataracts in cetaceans? How often do they affect vision?

What is normal IOP in cetaceans? How does sternal recumbency affect IOP?

What fundic diseases have been observed in cetaceans?

Answer 5

• Lens
  
  • Cataracts - 16% in recent survey; likely higher
  • Usually don’t progress to cause loss of vision like in pinnipeds
  • Lens subluxation in one case
• Glaucoma
  
  • Not diagnosed in dolphins
  • Can raise IOP really high during diving
  • 28-40mmHg normally
  • Sternal recumbency can increase IOP (60-80mmHg)
• Fundus
  
  • No issues diagnosed clinically but have been found histologically
    
    • Retinal detachment (older dolphins)
    • Retinal atrophy and pigment lipofuscinosis in a beluga

Question 6

Describe the unique anatomy & physiology of pinnipeds?

What is their corneal shape like? What does that accomplish?

What is their pupil shape?

How do they accomodate?

What does the fundus look like?

What is their tear film like? How does this compare with terrestrial mammals and cetaceans?

Answer 6

Pinnipeds

• Anatomy
  
  • Cornea: thick, thicker peripherally, thin Descemet’s membrane and endothelium
    
    • Flat plateau (reduces aerial myopia; oval in phocids, round in otariids & walrus
      
      • Phocids spend more time in water..?
  • Iris: pupil is tear drop shaped when relaxed
    
    • Thick circumferential muscle - accommodation function
  • Spherical lens
  • Ciliary body and muscle similar to terrestrial carnivores except that there is a thin transverse circumferential smooth muscle that subtends the pars plicata
  • Thick cellular tapetum lucidum; covers almost all of fundus
  • Prominent vascular plexus posterior to the globe surrounded optic nerve - temperature and oxygenation
• Physiology
  
  • No nasolacrimal system
  • TEL gland (not a harderian gland)
  • Main lacrimal gland beneath superior eyelid temporally
  • Tear film - have mucus and aqueous components but no lipid component (no meibomian glands!)
    
    • They do have sebaceous glands in outer eyelid skin and eyelid margin but they don’t contribute to tear film
    • Thick mucus layer (not as thick as cetaceans)
      
      • Secreted by goblet cells in conjunctiva

Question 7

Describe the progression of pinniped keratopathy.

What is the staging system?

What clinical signs are apparent?

What secondary infections can occur?

Answer 7

• Pinniped Keratopathy
  
  • Usually bilateral
  • 3 stages
    
    • Stage 1: perilimbal edema, pigment from conjunctiva to limbus, pinpoint gray corneal opacities +/- ulceration at dorsotemporal paraxial location. Variably painful. Epiphora, crusting, blepharospasm. Pinpoint opacities are like indolent ulcers (can do burr keratotomy to improve healing). If infected…
    • Stage 2: perilimbal edema, pigmentation more apparent, limbal hyperemia, vessels, 10-20% corneal opacity +/- ulceration/abscess formation, edema, bullae; indolent ulcers w/ stromal loss. Very painful when active. Opportunistic infections common (Psuedomonas, Enterococcus, E coli, Aspergillus, Candida). Can become quiescent.
    • Stage 3: 20-100% corneal opacity, ulceration , abscess, diffuse edema with stromal loss, pain, infection. Can progress to descemetoceles or perforated corneas. Can become quiescent. Size determines if a quiescent lesion is stage 2 or 3.
    • Amyloid deposition can occur over time

Question 8

Describe juvenile keratopathy in California sea lions.

What is its relationship to pinniped keratopathy.

Answer 8

• Juvenile CSL keratopathy
  
  • Variant of pinniped keratopathy @ 2-3yo
  • Mostly along pacific coast
  • Rapid onset, severe, diffuse edema, bullae
  • Tx: abx, NSAIDs, tramadol
  • Can predispose to pinniped keratopathy; may be delayed by using cyclosporine or tacrolimus
  • May have viral etiology

Question 9

Describe phocid and odobenid keratapathy.

What species are most severely affected?

What are common risk factors?

Answer 9

• Phocid Keratopathy
  
  • Harbor seals - acute corneal edema, blepharospasm, elevated nictitating membranes, secondary infections
    
    • Abrupt changes in water quality, UV exposure
  • Gray seals (Halicoerus grypus) - most aggressive keratopathy.
    
    • 3 stages
      
      • 1: <10% corneal, limbal hyperemia
      • 2: 10-20%, corneal vascularization
      • 3: dispersed pigment, edema, vascularization, White chalky superficial infiltrate (not identified)
  • Hawaiian monk seals (severe due to UV index in hawaii), harp seals
• Walrus Keratopathy
  
  • More similar to phocids than otariids.
  • 3 stages
    
    • 1: mild perilimbal an axial edema, pigment migration
    • 2: more diffuse opacity
    • 3: >20% cornea, diffuse edema, stormal loss, can progress to perf

Question 10

Describe treatment strategies for pinniped keratopathy.

How does UV exposure cause damage to the eyes? How can this be mitigated?

What is a general treatment approach to treating these eyes.

What other strategies can be implemented for control?

Answer 10

• Therapeutic strategies
  
  • Topical and oral abx
    
    • Shoudl address psuedomonas, coliform infections
    • Aminoglycosides (tobramycin or gentamicin), triple ointment, chloramphenicol, quinolones
    • Oral doxycycline
  • Palpebral lavage
  • NSAIDs - can slow epithelialization of corneal ulcers
  • Tramadol
  • Ulcer debridement
  • Decrease UV exposure
    
    • UV upregulates MMPs 2 and 9. Loss of keratocytes, stromal thinning, corneal vascularization/fibrosis and perforation
    • To inhibit MMP9 - oral doxy, tumeric, oral antioxidants like grapeseed, lutein, moega 3s, alha lipoic acid
• Basic treatment protocol
  
  • Acute mild to moderate blepharospasm + corneal edema + negative stain w/o obvious infection
    
    • Topical or oral NSAID
      
      • Ketorolac, nepafenac
      • Carprofen, meloxicam
    • If not improving in 2-3d, start topical and oral abx
  • Suspected secondary bacterial infection
    
    • Topical tobramycin and triple + oral doxycycline
    • Oral NSAIDs
    • Oral Tramadol
    • Enrofloxacin or cipro if not opening eye
• Control
  
  • Topical cyclosporine or tacrolimus → less intense flare ups and/or longer intervals between them
    
    • Implant

Question 11

What are risk factors associated with cataracts in pinnipeds?

What are some complications that can occur post-op?

What is typical IOP for pinnipeds?

How can glaucoma be treated in them?

Answer 11

• Lens
  
  • Cataracts, Instability
  • Factors: age, fighitng history, ocular dz, less shade (10x more likely if no shade)
  • Cataract tx
    
    • Surgery
      
      • Lensectomy and phacoemulsification
      • Ideal patient - progressive cataracts that have not luxated anteriorly
      • Complications: endophthalmitis, retinal detachment, concurrent corneal ulceration
      • Harbor seals seem to be predisposed to lipid keratopathy post op
      • Medial strabismus in CSLs w/ progressive cataracts
      • Lens capsules should be entirely removed due to aggressive anterior and posterior capsular opacification
    • Training for medications
    • Used to being dry docked
• Glaucoma
  
  • Usually secondary
  • Normal IOP 24-39mmHg; depends on temperament and demeanor
  • c/s: diffuse corneal edema and slight to moderate dilation of pupil in ambient light
  • Topical and oral carbonic anhydrase inhibitors + anti-inflammatory
    
    • Ex. dorzolamide, methazolamide
  • Topical prostagalndin analogs
• Fundus
  
  • Retinal detachment w/ chronic cataracts
    
    • Primarily in younger sea lions
  • Metastatic lymphoma in one case

Question 12

Describe the anesthesia of marine mammals for ophthalmic surgeries.

What neurmuscular blockage drugs can be used?

What is the vasovagal reflex?

How can this be prevented?

Answer 12

Anesthesia for Ophthalmic Surgery

• Sternal recumbency, slightly tilted, or lateral recumbency, head turned to position the eye
• Alpha 2’s problematic, esp w/ geriatric ophtho patients
  
  • Bradycardia, peripheral vasoconstriction, increased afterload
  • Reduce renal blood flow
  • Interferes w/ glucose homeostasis
  • Perioperative intraocular hemorrhage, high neg outcome (unpub data)
• Neuromuscular block
  
  • Needed to centralize and immobilize the eye
  • Delphinids lack plasma cholinesterase → depolarizing neuromuscular blocker, succinylcholine, was not recommended
  • Atracurium (undergoes simple Hofmann degradation (elimination)) used successfully in phocids, otariids, odobenids, and delphinids
    
    • Antagonist = edrophonium
      
      • Should be given slowly due to bradycardia
      • Future options: suggamadex + rocuronium
    • Assess w/ nerve stimulators (imprecise)
• Vasovagal reflex
  
  • Trigeminocardiac reflex - oculocardiac reflex
  • Cardiac arrest
  • Traction on extraocular muscles, exaggerated in presence of hypoventilation, hypoxemia and acidosis
  • Prevented by retrobulbar local block or parasympatholytic drugs

Question 13

What nutraceuticals may help prevent cataract formation in marine mammals?

Answer 13

Prophylaxis: Nutraceutical Antioxidants

• Lutein, zeathanthin, lycopene, astaxanthin are non-provitamin A carotenoids in plants, algae, vegetables and photosynthetic bacteria important in ocular health
• Accumulate in lens and retina- natural ocular cunblock
• Vitamin levels degraded in frozen fish that ate plants/algae when alive
• Lipid peroxidation during thawing making polyunsaturated FAs unstable
• Omega-3’s can help
• Vit E - highly concentrated in rod outer segments and retinal pigment epithelium; can protect vitA from degradation
• Rancidity - vit E consumption
• Grape seed extract and alpha lipoic acid → potentiate effects of vit C, E. inhibit cataract formation in animal models