A retrospective survey of the ocular histopathology of the pinniped eye with emphasis on corneal disease Sarah Miller,* Carmen M. H. Colitz,† Judy St. Leger‡ and Richard Dubielzig* *School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA; †Aquatic Animal Eye Care, Jupiter, FL 33458, USA; and ‡Director of Pathology Sea World, San Diego, CA 92109, USA Address communications to: S. Miller Tel.: +602 380 3087 Fax: +608 262 9150 e-mail: sarahmiller588@gmail. com Abstract Objective A retrospective review of globes from 70 pinnipeds submitted to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) describing the type and frequency of ocular disease. Animals studied The study included 50 California sea lions, four animals listed only as ‘sea lion’, nine Northern elephant seals, five harbor seals, 1 Northern fur seal, and 1 Hooded seal. Procedures Globes were classified by microscopic findings. Categories were not mutually exclusive. Results The largest category was corneal disease (63 globes from 40 pinnipeds). The second largest was cataractous changes (35 globes from 23 pinnipeds). Additional ocular diseases included traumatic ocular injuries (nine globes from eight animals), phthisis bulbi (nine globes from eight pinnipeds), neoplasia (nine globes from six adult California sea lions), amyloid deposition in the corneal stroma, ciliary body, or both locations (five globes from four pinnipeds), and fungal disease (three globes from two pinnipeds). Pinnipeds with corneal disease were further categorized: stromal pathology (39 globes from 27 pinnipeds); epithelial pathology (37 globes from 27 pinnipeds); Descemet’s pathology (11 globes from eight pinnipeds); endothelial attenuation or absence (33 globes from 22 pinnipeds); presence of retrocorneal membranes (15 globes from 10 pinnipeds); anterior synechia (eight globes from six animals), and keratitis (seven globes from five pinnipeds). Conclusions This is the first report of ocular amyloid in pinniped eyes. All cases of neoplasia were in a pattern suggesting metastatic disease. In this study, there was a higher prevalence of ocular disease in captive pinnipeds, particularly in the posterior cornea. Key Words: amyloid, cataract, corneal disease, ocular pathology, pinniped, sea lion INTRODUCTION Pinnipeds are one of the few mammalian species with the ability to see well above and below water and also to maintain useful vision in the dim light environment of deep dives. Adaptations include a flattened cornea to reduce aerial refraction; a round, dense lens to provide adequate refraction; and a highly developed cellular tape- tum lucidum to allow adequate light for vision at depth combined with a pupil capable of extreme constriction to protect the retina in aerial daylight. Pinnipeds develop a significant amount of ocular disease in both captivity and the wild. 1–5 Suspected factors contributing to ocular lesions in captive pinnipeds are age, history of fighting, history of ocular dis- ease, and lack of shade. 6,7 Inadequate shade, which was found to increase the likelihood of ocular disease by ten-fold in a study by Colitz et al., 6 is thought to be the largest factor. Although less common because of newer recommendations, another possible reason for consistent ocular issues in pinni- peds under human care includes housing in freshwater pools. 1,8 Common ocular pathology found in captive pinnipeds includes corneal lacerations, corneal edema or other opaci- ties, keratitis, cataractous changes, and lens luxations. 1,3,6,7,9 Ocular trauma and cataractous changes are commonly found Ó 2012 American College of Veterinary Ophthalmologists Veterinary Ophthalmology (2012) 1–11 DOI:10.1111/j.1463-5224.2012.01040.x
Transcript
A retrospective survey of the ocular histopathology of the pinnipedeye with emphasis on corneal disease
Sarah Miller,* Carmen M. H. Colitz,† Judy St. Leger‡ and Richard Dubielzig**School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA; †Aquatic Animal Eye Care, Jupiter, FL 33458, USA; and ‡Director
of Pathology Sea World, San Diego, CA 92109, USA
Address communications to:
S. Miller
Tel.: +602 380 3087
Fax: +608 262 9150
e-mail: sarahmiller588@gmail.
com
AbstractObjective A retrospective review of globes from 70 pinnipeds submitted to theComparative Ocular Pathology Laboratory of Wisconsin (COPLOW) describing the
type and frequency of ocular disease.Animals studied The study included 50 California sea lions, four animals listed only as
‘sea lion’, nine Northern elephant seals, five harbor seals, 1 Northern fur seal, and 1Hooded seal.
Procedures Globes were classified by microscopic findings. Categories were notmutually exclusive.
Results The largest category was corneal disease (63 globes from 40 pinnipeds). Thesecond largest was cataractous changes (35 globes from 23 pinnipeds). Additionalocular diseases included traumatic ocular injuries (nine globes from eight animals),
phthisis bulbi (nine globes from eight pinnipeds), neoplasia (nine globes from sixadult California sea lions), amyloid deposition in the corneal stroma, ciliary body, or
both locations (five globes from four pinnipeds), and fungal disease (three globes fromtwo pinnipeds). Pinnipeds with corneal disease were further categorized: stromal
pathology (39 globes from 27 pinnipeds); epithelial pathology (37 globes from 27pinnipeds); Descemet’s pathology (11 globes from eight pinnipeds); endothelial
attenuation or absence (33 globes from 22 pinnipeds); presence of retrocornealmembranes (15 globes from 10 pinnipeds); anterior synechia (eight globes from sixanimals), and keratitis (seven globes from five pinnipeds).
Conclusions This is the first report of ocular amyloid in pinniped eyes. All cases ofneoplasia were in a pattern suggesting metastatic disease. In this study, there was a
higher prevalence of ocular disease in captive pinnipeds, particularly in the posteriorcornea.
Pinnipeds are one of the few mammalian species with theability to see well above and below water and also tomaintain useful vision in the dim light environment ofdeep dives. Adaptations include a flattened cornea toreduce aerial refraction; a round, dense lens to provideadequate refraction; and a highly developed cellular tape-tum lucidum to allow adequate light for vision at depthcombined with a pupil capable of extreme constriction toprotect the retina in aerial daylight. Pinnipeds develop asignificant amount of ocular disease in both captivity andthe wild.1–5
Suspected factors contributing to ocular lesions in captivepinnipeds are age, history of fighting, history of ocular dis-ease, and lack of shade.6,7 Inadequate shade, which wasfound to increase the likelihood of ocular disease by ten-foldin a study by Colitz et al.,6 is thought to be the largest factor.Although less common because of newer recommendations,another possible reason for consistent ocular issues in pinni-peds under human care includes housing in freshwaterpools.1,8
Common ocular pathology found in captive pinnipedsincludes corneal lacerations, corneal edema or other opaci-ties, keratitis, cataractous changes, and lens luxations.1,3,6,7,9
Ocular trauma and cataractous changes are commonly found
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ocular pathologies noted in wild pinnipeds.4,8 Wild North-ern fur seals (Callorhinus ursinus) were found to have cornealscars, prominent cataractous change in the area of the lenssutures, cataracts, and iris depigmentation but not cornealedema or active ulceration or inflammation.10
This study catalogues ocular pathology, with an emphasison corneal disease, in captive and wild pinniped eyes submit-ted to the Comparative Ocular Pathology Lab of Wisconsinover the past 20 years.
MATERIAL AND METHODS
Globes from 70 pinnipeds submitted to and archived at theComparative Ocular Pathology Laboratory of Wisconsin(COPLOW) were analyzed to determine the ocular diseasespresent. The study included 50 California sea lions (Zalophuscalifornianus), four animals listed only as ‘sea lion’, nineNorthern elephant seals (Mirounga angustirostris), five har-bor seals (Phoca vitulina), 1 Northern fur seal (Callorhinusursinus), and 1 Hooded seal (Cystophora cristata). Animalswere submitted with both numerical age values (captive ani-mals) and age categories: pup, juvenile, adult. Animals sub-mitted with a numerical age were divided into similarcategories: ‘pup’ consisting of all animals labeled as pups oras 1 year or less in their history, ‘juvenile’ consisting of allanimals labeled as juvenile or as 2–7 years old in their his-tory, and ‘adult’ which consisted of all animals listed as adultor >7 years old in their history. One animal listed as ‘youngadult’ was also put into the ‘adult’ category. These agegroups were chosen because the onset of puberty variesbetween 2 and 7 years in pinnipeds.11 Animals were alsodivided according to their sex and whether their historylabeled them as ‘captive’ or ‘wild’ animals. The historicaldata given to us do not clarify whether animals listed as ‘cap-tive’ were born in captivity or born in the wild and trans-ferred into captivity later in life. Age, sex, and captive/wildstatus are noted in Tables 1–4.
Eyes were examined microscopically using paraffin-embedded ocular tissue sections stained with hematoxylinand eosin. Globes were sectioned primarily in the dorsoven-tral plane. Five globes were sectioned in the oblique orlateromedial planes. Five globes from three animals weresectioned horizontally. Globes with glassy collagen charac-teristic of amyloid were additionally stained with CongoRed and viewed under cross-polarized light.
Lesions were divided into eight generalized categories:normal, fungal disease, corneal disease, cataract, neoplasia,trauma, phthisis bulbi, and the presence of amyloid material.Animals were placed into multiple categories when appro-priate.
RESULTS
Forty-seven globes from 30 pinnipeds were classified asnormal. Among the 24 pinnipeds where we received botheyes, seven had unilateral ocular disease. The most
common disease contralateral to a normal eye was cornealdisease without inflammation See Table 1 for furtherbreakdown.
Pathology was noted in 79 globes from 47 animals. Abreakdown of the types of ocular disease found is detailed inTable 2 and summarized in Table 3. The largest categorywas corneal disease with 63 globes from 40 animals (Fig. 1).The types of corneal disease are listed in Table 4. The sec-ond largest category, presence of cataract, included 35globes from 23 animals. Captive animals were overrepre-sented with comparison to wild animals (16 and 6, respec-tively). In pinnipeds where we received both globes withinterpretable lenses, bilateral cataracts were twice as com-mon (12 and 6 cases, respectively). In 3 of the 21 animalswhere we received both globes, the lens was uninterpretablein one globe. Including these three animals, there were atotal of 16 globes from 12 animals with lenses that were notevaluated because of inadequate sectioning. See Table 5 forfurther breakdown of pinnipeds with lens pathology. Addi-tional ocular diseases found, summarized in Table 3 anddetailed in Table 2, include nine globes from eight animalswith lesions interpreted as traumatic ocular injuries, nineglobes from eight pinnipeds with phthisis bulbi, nine globesfrom six pinnipeds with neoplasia, five globes from four ani-mals with amyloid deposition, and three globes from twopinnipeds with fungal disease (Fig. 2, 3).
All six pinnipeds with neoplasia were adult California sealions. There were two metastatic adenocarcinomas and onemetastatic epithelial neoplasia in three captive females.There was one case of lymphoma in a captive male and onemetastatic round cell neoplasia in a wild female (Fig. 4).
There were four cases of amyloid deposition, three malesand 1 female. All cases were captive adult California sealions. Both eyes were received in all cases, but amyloid depo-sition was only bilateral in one animal. Amyloid material waslocated in either the corneal stroma, ciliary body, or bothlocations (Fig. 5).
Corneal diseaseCorneal disease was broken down into seven categories:keratitis (inflammatory corneal disease), epithelial pathol-ogy, stromal pathology, endothelial pathology, Descemet’smembrane pathology, retrocorneal membranes, and ante-rior synechia. Disease related to extensive trauma, such asperforation or phthisis bulbi, was omitted from this cate-gory. Globes were placed in every related category.Results are summarized in Table 6 and detailed inTable 4. The largest category was stromal pathology with39 globes from 27 animals. The next largest categorieswere epithelial and endothelial pathology with 37 globesfrom 27 animals and 33 globes from 22 animals, respec-tively. There were 15 globes from 10 animals with retro-corneal membranes, 11 globes from eight animals withDescemet’s pathology, eight globes from six animalswith anterior synechia, and seven globes from five animalswith keratitis.
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A relative comparison of corneal disease between captiveand wild pinnipeds is shown in Fig. 6. Anterior corneal dis-ease (epithelial and stromal disease) was the predominantocular disease in wild pinnipeds. Epithelial pathology aloneaccounted for nearly half of all ocular pathology docu-mented. Keratitis and Descemet’s membrane pathology wasnot found in wild pinnipeds. There was a more balancedratio to the diseases in captive pinnipeds, with a slight preva-lence to posterior corneal disease (endothelial and Desc-emet’s membrane disease and the presence of retrocornealmembranes or anterior synechia).
Stromal diseases included hypercellularity, remodeling,edema, fibrovascularization, collagenolysis, and full-thick-ness corneal rupture (Fig. 7). Hypercellularity was charac-terized by increased numbers of spindle cells in the stroma.Remodeling was characterized by a qualitative change in thecollagen of the stroma and loss of the normal lamellar struc-ture of the corneal stroma. Stromal edema was characterizedby a thickened stroma with a washed out appearance or byswelling of epithelial cells or extracellular vacuoles in theepithelium. Fibrovascularization was characterized by acombination of remodeling and blood vessel proliferation inthe stroma. Collagenolysis was characterized by liquefiedstromal collagen with potential corneal rupture. There wasalso one case with melanin pigment deposition and one case
with stromal thinning Table 7. Summarizes the types of cor-neal disease found in this study.
Epithelial pathology included separation, disorganization,downgrowth, thickening, thinning, absence, reattachment,nonattachment, ulcers with, and one without, re-epithelial-ization (Fig. 8). Separation was characterized by the forma-tion of a cavitation anywhere within the epithelium.Disorganization was characterized by abnormal clusters ofcells, formation of squamous eddy, inappropriate keratiniza-tion, or dysplastic nuclear features. Downgrowth was char-acterized by epithelial tissue extending into the cornealstroma. Thickening was characterized by acanthosis orhyperkeratosis. Reattachment was characterized by markedthickening of the basal lamina, newly formed stroma, or theformation of a facet lesion. Ulceration was characterized bya defect in the anterior stroma but not covered by epithe-lium. Reepithelialized ulcers were characterized by a stromaldefect which has been covered again by epithelium oftenwith an indentation or sometimes with the epithelial compo-nent reforming a smooth surface. See Table 7 for summary.
The normal corneal endothelium is thinner and populatedby attenuated cells when compared with what is seen in mostmammals (Fig. 9). Endothelial pathology included attenua-tion and absence (Fig. 10). Descemet’s membrane pathologyincluded wrinkling, disruption, doubling, and one case with
Table 1. Normal globes
Species Age Sex Normal globes Abnormal globe
California sea lion W A F X OUCalifornia sea lion W A F I OUCalifornia sea lion W A F I OUCalifornia sea lion W A F I OD OS-corneaCalifornia sea lion W A F I OUCalifornia sea lion W A F I OUCalifornia sea lion W A F I OUCalifornia sea lion W A F I OUCalifornia sea lion W A F I OD OS-corneaCalifornia sea lion W J F I OUCalifornia sea lion W J M X OS OD-cataractCalifornia sea lion W X F X OSCalifornia sea lion W X F X XCalifornia sea lion W X F X XCalifornia sea lion W X F X OUCalifornia sea lion W X F X OUCalifornia sea lion W X F X OUCalifornia sea lion W X M X XCalifornia sea lion W X X X OD OS-corneaCalifornia sea lion C J M N OUCalifornia sea lion C J M I OUCalifornia sea lion X J F I OS OD-corneaSea lion C A M I OSSea lion X A M I OD OS-corneaNorthern elephant seal W A M X OD OS-corneaNorthern elephant seal W J F X OUNorthern elephant seal W P F X OUNorthern elephant seal X P F X OUNorthern elephant seal W X X X OUNorthern fur seal X X X X X
W, wild; C, captive; A, adult; J, juvenile; P, pup; I, intact; N, neutered; X, unknown (in ‘normal globe’, X = 1 globe, unknown whether OS or OD).
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thickening. The presence of retrocorneal membranes andanterior synechia was also noted. See Table 7 for summary.
DISCUSSION
Neoplasia is found significantly more frequently in Califor-nia sea lions than in other pinnipeds.1,4,12,13 Bowen et al.14
attributed this to the presence of certain class II MHCgenes. Other authors have suggested that the frequency andmortality rate because of neoplasia in California sea lions
may be exacerbated by inbreeding and the accumulation oforganochlorides, specifically polychlorinates biphenyls(PCBs).15,16 The neoplasm most often reported in Califor-nia sea lions is of transitional cell origin and speculated to berelated to Otarine Herpesvirus-1.4,17–19 Newman and Smith(2006) summarized the type and location of neoplasia inmarine mammals reported by previous studies. Neoplasiahas been found in nearly every organ of California sea lions,often with widespread metastasis.12 The ocular neoplasiafound in our study was only in adult California sea lions. In
Table 2. Abnormal globes, detailed
Species Age Sex OS OD X
California sea lion C A F I Co, ca Co, caCalifornia sea lion C A F I tr, ne, co, ca ne, co, caCalifornia sea lion C A F I – co, caCalifornia sea lion C A F X co, ca ne, co, caCalifornia sea lion C A F I co, ca co, caCalifornia sea lion C A F I ph, f, co, ca –California sea lion C A F X ne amCalifornia sea lion C A M I am, ph, co, ca coCalifornia sea lion C A M I co am, coCalifornia sea lion C A M N co coCalifornia sea lion C A M N co, ca co, caCalifornia sea lion C A M N co co, caCalifornia sea lion C A M I co co, caCalifornia sea lion C A M I am, co, ca am, co, caCalifornia sea lion C A M I co, ca co, caCalifornia sea lion C A M I co coCalifornia sea lion C A M I ph, tr, co, ca ph, trCalifornia sea lion C A M I ca, co ca, co trCalifornia sea lion C A M N ne neCalifornia sea lion W A F I co nCalifornia sea lion W A F I ne ne, caCalifornia sea lion W A F X co coCalifornia sea lion W A F I co nCalifornia sea lion W A F I co coCalifornia sea lion W A F I co coCalifornia sea lion W X F I co ph, trCalifornia sea lion W J M I ph, co coCalifornia sea lion W J M I ca caCalifornia sea lion W J M X n caCalifornia sea lion W X M I ph, tr, co ne, co, caCalifornia sea lion W X X X co nCalifornia sea lion X J F I n coCalifornia sea lion X X X X – – coHarbor seal C A F I co, ca co, caHarbor seal C A M I f, co, ca f, coHarbor seal C A M I tr, co –Harbor seal W P F I ph, tr –Harbor seal X A m X ca co, caHooded seal X X X X – – coNorthern elephant seal W J F X – coNorthern elephant seal W A M X co nNorthern elephant seal W J M X co –Northern elephant seal W P M X ph, tr, co, ca coNorthern elephant seal W X M X ca caSea lion C X X X – – coSea lion C X X X co coSea lion X A M I co n
W, wild; C, captive; A, adult; J, juvenile; P, pup; I, intact; N, neutered; co, corneal disease; ca, cataract; neo, neoplasia; tr, trauma; ph, phthisisbulbi; am, amyloid; f, fungal; N, normal (only included if the opposing eye had disease); X, unknown.
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all cases, the neoplasia was in a pattern suggesting that it wasmetastatic; however, aside from one case of lymphoma, theexact tumor type was not apparent from the ocular samples.
Amyloid, a fibrillar misfolding of protein where the pep-tides bond in the form of a beta pleated sheet, is a complexphenomenon that can be found in many tissues of the body.Although there are many unrelated proteins that fall underthe category of amyloid, they all share certain characteris-tics; they stain with Congo red and display a green birefrin-gence in polarized light. By electron microscopy, amyloidhas characteristic 75–100A thick filaments, and the polypep-tide chains in these filaments run transversely (beta pleated-sheet pattern). The histological appearance of amyloid is aneosinophilic hyaline material. Solid forms of amyloid appear
to cause little to no damage and do not initiate an immuneresponse.20 Amyloid deposition can occur as a ‘primary’ dis-ease or ‘secondary’ to another illness, typically chronic
Table 3. Summary of Tables 1 and 2
Globes Animals
Total included in study 126 70No pathology 47 30Corneal pathology 63 40Cataract changes 35 23Traumatic injury 9 8Phthisis bulbi 9 8Neoplasia 9 6Amyloid deposition 5 4Fungal disease 3 2
Table 4. Corneal disease, detailed
Species
Corneal Dz
Additional DzAge Sex Eye OS OD X
California sea lion C A F I OU ep, en ep, en st CataractCalifornia sea lion C A F I OD ep, st, de, me CataractCalifornia sea lion W J M I OU st en PhthisisCalifornia sea lion C A F X OU ke, st, en, me, sy ke, st, en, de, me, sy Neo/cataractCalifornia sea lion W X M I OU ep, st, sy st, en Phthisis/trauma/neo/cataractCalifornia sea lion W X F I OU ep Phthisis/traumaCalifornia sea lion W X X X OU ep NormalCalifornia sea lion C A M I OU sy ep, st Amyloid/cataract/phthisisCalifornia sea lion C A M I OU ep, en ep, en CataractCalifornia sea lion C A M I OU ep, st Phthisis/cataract/traumaCalifornia sea lion W A F X OU st, en st, en, meCalifornia sea lion C A M I OU ep, st, en, me ep, de, me AmyloidCalifornia sea lion W A F I OU ep NormalCalifornia sea lion W A F I OU ep, st NormalCalifornia sea lion W A F I OU ep epCalifornia sea lion W A F I OU ep epCalifornia sea lion C A M I OU ep, st ep, st Amyloid/cataractCalifornia sea lion C A M I OU ep, st, en, de st, en, de, me CataractCalifornia sea lion C A M N OU ep, st, en ep, en CataractCalifornia sea lion X J F I OU st NormalCalifornia sea lion C A M I OU ep, st, en, de, me ep, st, en, de, meCalifornia sea lion C A F I OU en en CataractCalifornia sea lion C A M N OU ke, st, en, de, me ke, st, en, de, me CataractCalifornia sea lion C A F I OU ep en Neo/trauma/cataractCalifornia sea lion C A M I OU st st en Trauma/cataractCalifornia sea lion C A F I OS ke, sy Fungal/phthisis/cataractCalifornia sea lion C A M N OU st stCalifornia sea lion X X X X X ep, enHarbor seal C A F I OU ep, st, en ep, st, en de, me CataractHarbor seal C A M I OS st, sy TraumaHarbor seal C A M I OU ep, st, en, me, sy ep, st, en, me, sy Fungal/cataractHarbor seal X A M X OU en CataractHooded seal X X X X X ke, stNorthern elephant seal W J F X OD enNorthern elephant seal W A M X OU ep NormalNorthern elephant seal W J M X OS ep, st, enNorthern elephant seal W P M X OU st ep Phthisis/trauma/cataractSea lion C X X X X ep, st, enSea lion C X X OU st st ep, en, de, meSea lion X A M I OU ke, ep, st Normal
C, captive; W, wild; A, adult; F, Female; M, Male; I, intact; N, neutered; st, stromal pathology; ep, epithelial pathology; en, endothelial pathol-ogy; me, retrocorneal membranes present; de, Descemet’s membrane disease; sy, anterior synechia; X, unknown, when OS, OD, and X are filledin, globes were labeled as only 1 & 2 so all unilateral disease was placed in the X column.
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inflammation or neoplasia. Primary and secondary amyloidsappear identical under light microscopy, and additionaldiagnostics are required to differentiate between them.
Amyloid deposition can also be classified as either systemicor localized.21
Secondary systemic amyloidosis has been noted in Cali-fornia sea lions by previous studies. These studies foundamyloid deposition in kidneys, small and medium arterioles,thyroid glands, liver, vaginal Bartholin glands, spleen, andgastric and intestinal mucosa.22,23 There is no mention ofamyloid deposition in the eye in either study; however,globes were not consistently sampled in the study by Cole-grove et al. (personal communication with Dr. Colegrove).Similar to this study, all California sea lions with amyloidpresent were adults; however, the study by Colegrove et al.22
only included stranded wild pinnipeds, whereas this studyonly found amyloid material in captive California sea lions.
(a) (b)
Figure 2. Gross images of globes sectioned in the sagittal plane from
two animals with phthisis bulbi showing atrophy and collapse of ocular
tissues associated with long standing severe disease.
Table 5. Cataractous changes
Species Age Sex Eyes received Lens pathology Additional category(s)
California sea lion C A M I OU OS Amyloid/corneaCalifornia sea lion C A M I OU OU Amyloid/corneaCalifornia sea lion W J M I OU OUCalifornia sea lion C A F I OU OU CorneaCalifornia sea lion C A F I OU OU CorneaCalifornia sea lion C A F I OD OD CorneaCalifornia sea lion C A M I OU OD CorneaCalifornia sea lion C A M I OU OU CorneaCalifornia sea lion C A M N OU OU CorneaCalifornia sea lion C A F X OU OU Neo/corneaCalifornia sea lion C A F I OU OU Neo/cornea/traumaCalifornia sea lion W X M I OU OD Phthisis/trauma/corneaCalifornia sea lion C A F I OS OS Fungal/phthisisCalifornia sea lion W J M X OU OD NormalCalifornia sea lion W A F I OU OD NeoCalifornia sea lion C A M I OU OU (as per gross) Trauma/corneaHarbor seal C A F I OU OU CorneaHarbor seal X A M X OU OU CorneaNorthern elephant seal W X M X OU OUNorthern elephant seal W P M X OU OS Phthisis/trauma/corneaCalifornia sea lion C A M N OU OD* CorneaCalifornia sea lion C A M I OU OS* Phthisis/corneaHarbor seal C A M I OU OS* Fungal/cornea
*The alternate globe in these cases was not sectioned appropriately for evaluation.W, wild; C, captive; A, adult; J, juvenile; P, pup; I, intact; N, neutered; X, unknown.
(a) (b)
(c) (d)
Figure 1. Gross photographs showing the cornea from four animals:
(a) Gross image of the cornea showing diffuse but variable grey-white
opacity and pigment (arrow). (b) Gross image of the cornea showing
regional grey-white opacity and pigment (arrow). (c) Gross image of
cornea showing a more profound opacity and pigment (arrow). (d)
Gross image of the globe sectioned in the sagittal plane showing axial
corneal stromal opacity.
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In addition, this study does not have adequate history todetermine whether the amyloidosis present is localized tothe cornea or systemic.
In this study, animals with the presence of amyloid mate-rial are all captive adult California sea lions. The amyloidmaterial was present within the corneal stroma and the cili-ary body. The bilateral case had amyloid material presentonly in the cornea. The female had amyloid material presentonly in the ciliary body, and the other two cases had amyloidmaterial in both. In all cases, the amyloid material stains redwith Congo red and shows green birefringence under polar-ized light (Fig. 5). Additional diagnostics to determinewhether the amyloid present was primary or secondary wasnot done.
Amyloid-like deposition in the ciliary body of the horsehas been found in association with Equine Recurrent Uve-itis.24 Primary localized corneal stromal amyloid depositionis found in human disorders such as hereditary lattice cor-neal dystrophy, polymorphic amyloid degeneration, andgelatinous drop-like corneal dystrophy.25–30 Corneal amy-loid deposition is also seen in association with climatic drop-let keratopathy in humans.31 Secondary corneal amyloidosisis found associated with interstitial keratitis and may be anonspecific finding in corneal with chronic disease.25,30,32
To remain clear, the cornea needs to maintain a delicatebalance of dehydration/deturgescence, largely controlled by
the endothelium and epithelium. Damage to either structurecan lead to edema and loss of vision because of cornealclouding. In humans, ultraviolet radiation exposure has beenshown to cause chronic diseases, such as climatic dropletkeratopy, pterygium, and endothelial dystrophy.33–35 Pinni-peds are exposed to excessive amounts of ultraviolet radia-tion both from their inadequately shaded, outdoor habitat aswell as from reflection of water. Most facilities have lightlycolored pool walls and surfaces around the pools to show-case the animals better. However, this color of paint does
(a) (b)
(c) (d)
Figure 3. Montage images of the same case with mycotic infection
and secondary inflammation: (a) Gross image of the sectioned globe
showing collapse of the lens secondary to hypermature cataract and
uveal and retinal thickening due to inflammation (box). (b) Photomicro-
graph showing the retinal area within the box of [A]. Mixed inflamma-
tion extends into the vitreous (Arrow). Bar = 60 l (c) Photomicrograph
showing pyogranulomatous inflammation within the box in [b]
Bar = 25 l. Numerous multinucleate giant cells (arrows) are seen along
with neutrophils. (d) Photomicrograph of silver stained tissue from [c]
showing mycotic hyphae. Bar = 15 l.
(a) (b)
(c) (d)
Figure 4. Montage of images from the same case with metastatic neo-
plasia: (a) Gross image of the sectioned globe showing thickening of the
uvea due to neoplastic infiltration. (b) Photomicrograph showing the
thickened tissue within the box from [a]. Bar = 90 l. Poorly defined
basophilic areas are evidence of neoplastic infiltration. (c) Photomicro-
graph of immunohistochemical stain for cytokeratin showing positive
brown staining of neoplastic epithelial cells from the area in the box in
[b]. Bar = 30 l. (d) Photomicrograph of tissue stained with H&E show-
ing neoplastic epithelial cells within blood vessels in the choroid.
Bar = 20 l.
(a) (b)
Figure 5. Photomicrographs showing the presence of amyloid in the
corneal stroma. (a) Section stained with H&E. (b) Section stained with
Congo Red showing amyloid material staining red and insert showing
birefringence when polarized.
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not absorb UV to any significant amount. Dangerous levelsof UV radiation have been shown to penetrate more than1 m in clear water; therefore, being under water does notprotect the animals from the damaging effects of UV.36–38
Pool colors that absorb UV include tan or natural ocean bot-tom colors as well as dark colors. Newer recommendationsare suggesting that facilities change the enclosures to protectthe animals’ eyes from UV reflection by painting them dar-ker colors.10
Excessive exposure to UV light, as well as history of fight-ing, previous ocular disease, and age are also related toincreased cataract formation.6,7 In the present study, cata-racts were the second most common disease, second to cor-neal disease, with 35 globes from 23 affected animals. Themajority of animals were captive (16 of 23). Eighteen of the23 animals with cataracts were adults. Fifteen of the 23 weremales, while only eight were females. The over-representa-
tion of males may be due to a higher number of males in cap-tivity, compared with females. It must also be taken intoconsideration that some of the animals submitted as ‘captive’may have been born in the wild and transferred into captivityat a later point in their life.
Bellhorn et al.39 suggested that transient corneal opacitiescould be caused by intense miosis, causing the iris leaflets tocontact and damage the corneal endothelium. However,other studies have documented a relatively deep anteriorchamber, which would suggest another mechanism of dis-ease, such as environmental insult.3 Under intense miosis,the iris does not touch the corneal endothelium; however,intermittent lens luxation prior to permanent anterior luxa-tion damages the endothelium. This intermittent luxation isoften not witnessed because it occurs at night. By the morn-ing, the lens will reposition itself behind the iris. With time,the lens becomes permanently anteriorly luxated with endo-thelial and posterior stromal damage ensuing rapidly. Envi-ronmental insults that could cause ocular damage includeoxidative compounds such as water quality issues, includingosmolality, and UV radiation in captive pinnipeds. (Colitz,personal observations) In our study, 22 of the 27 (81.5%)captive pinnipeds had ocular disease while 13 of the 37(35.1%) wild pinnipeds had ocular disease. These numberssuggest a higher risk of ocular disease in the pinniped popu-lation under human care, but should be investigated with amore controlled population to eliminate the possibility ofselection bias. We found that disease location in pinnipeds
Section showing full thickness corneal stromal fibrosis and vascular
infiltrate (arrows). Bar = 20 l. (b) Section showing disorganization and
tissue remodeling of the superficial most stroma subtending the epithe-
lium (arrows). Bar = 60 l. (c) Section showing stromal thinning. (*) (d)
Section showing hypercellular and disorganized stroma adjacent to
Descemet’s membrane (arrows).
8 m i l l e r E T A L .
� 2012 American College of Veterinary Ophthalmologists, Veterinary Ophthalmology, 1–11
labeled as captive was more evenly balanced between theanterior and posterior corneal disease, with posterior cor-neal disease slightly more prevalent (Fig. 6), whereas diseasein wild pinnipeds was predominately anterior cornealdisease.
Corneal pathologic specimens were divided into sevencategories, some being in more than one grouping. Stromaldisease was the most common finding with epithelial andendothelial disease also common. These changes may beconsistent with recently described Otariid Keratitis occur-ring in eared seals under human care.7 Specific pathologicfindings in our study were epithelial thinning, endothelialattenuation, stromal hypercellularity, stromal fibrovascular-ization, stromal remodeling, and retrocorneal membranes.Chronic exposure to UV may have exacerbated corneal dis-ease in this species, but we are unable to say that UV is theprimary etiology for all of these findings. The corneal epi-thelium can only tolerate a maximum UVB radiation dose;once this threshold is met, the normal epithelial cell shed-ding process and homeostasis become disrupted.40 The epi-thelial cells then undergo apoptosis and slough exposingsuperficial corneal nerves and resulting in clinical signs ofpain.41 Stromal thinning can be caused by chronic UV expo-sure.42 Unstable tear film is also possibly contributing tocorneal disease in these animals, and we are collaboratingwith tear film experts and anatomists to determine what rolethis may play in pinniped corneal disease. Retrocornealmembranes may be more likely due to intermittent orchronic anterior lens luxations.
In summary, corneal and lens diseases were the most pre-valent ocular findings in this collection. Both are common inpinnipeds of all ages and in wild animals and those underhuman care. In this study, there was a higher prevalence ofocular disease in pinnipeds under human care, particularlyin the posterior cornea. This is the first report of ocular amy-loid in pinniped eyes. Based on the human literature, thismay also be a nonspecific finding in chronic interstitial cor-neal disease. All cases of neoplasia were in a pattern suggest-ing metastatic disease and only occurred in California sealions.
