Characteristics of, prevalence of, and risk factors for corneal pigmentation (pigmentary keratopathy) in Pugs

Amber L. Labelle Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61082.

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Christine B. Dresser Department of Cuyahoga Valley Veterinary Clinic, 3850 Brecksville Rd, Richfield, OH 44286.

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Ralph E. Hamor Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61082.

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Matthew C. Allender Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61082.

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Julia L. Disney Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61082.

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Abstract

Objective—To determine the characteristics of, prevalence of, and risk factors for corneal pigmentation (CP) in Pugs.

Design—Prospective cross-sectional study.

Animals—295 Pugs > 16 weeks old.

Procedures—Ophthalmic examination of the anterior segment of each eye was performed, including determination of tear film characteristics (Schirmer tear test and tear film breakup time) and corneal sensitivity. Digital photographs of the head and each eye were obtained. Corneal pigmentation of eyes was graded as absent, very mild, mild, moderate, or severe. Signalment and medical history information and American Kennel Club registration status were recorded.

Results—CP was detected in at least 1 eye of 243 of the 295 (82.4%) Pugs; CP was typically very mild or mild. Detection of CP was not significantly associated with coat color, age, eyelid conformation, or tear film characteristics but was significantly associated with sex of dogs. The severity of CP was not significantly associated with American Kennel Club registration status or age, but was significantly associated with sex, tear film characteristics, and coat color. Iris hypoplasia was detected in 72.1% of the Pugs. Iris-to-iris persistent pupillary membranes were detected in 85.3% of the Pugs.

Conclusions and Clinical Relevance—Prevalence of CP in Pugs in this study was high. Unexpectedly high prevalences of iris hypoplasia and persistent pupillary membranes were also identified. The condition identified in these Pugs was a pigmentary keratopathy, rather than pigmentary keratitis or corneal melanosis. This condition may have a genetic basis, and further studies are warranted to determine etiology.

Abstract

Objective—To determine the characteristics of, prevalence of, and risk factors for corneal pigmentation (CP) in Pugs.

Design—Prospective cross-sectional study.

Animals—295 Pugs > 16 weeks old.

Procedures—Ophthalmic examination of the anterior segment of each eye was performed, including determination of tear film characteristics (Schirmer tear test and tear film breakup time) and corneal sensitivity. Digital photographs of the head and each eye were obtained. Corneal pigmentation of eyes was graded as absent, very mild, mild, moderate, or severe. Signalment and medical history information and American Kennel Club registration status were recorded.

Results—CP was detected in at least 1 eye of 243 of the 295 (82.4%) Pugs; CP was typically very mild or mild. Detection of CP was not significantly associated with coat color, age, eyelid conformation, or tear film characteristics but was significantly associated with sex of dogs. The severity of CP was not significantly associated with American Kennel Club registration status or age, but was significantly associated with sex, tear film characteristics, and coat color. Iris hypoplasia was detected in 72.1% of the Pugs. Iris-to-iris persistent pupillary membranes were detected in 85.3% of the Pugs.

Conclusions and Clinical Relevance—Prevalence of CP in Pugs in this study was high. Unexpectedly high prevalences of iris hypoplasia and persistent pupillary membranes were also identified. The condition identified in these Pugs was a pigmentary keratopathy, rather than pigmentary keratitis or corneal melanosis. This condition may have a genetic basis, and further studies are warranted to determine etiology.

Corneal pigmentation develops as a result of a local biological response to various irritating stimuli.1 Such stimuli may be mechanical, such as corneal surface abrasion by eyelid skin (entropion) or aberrant hair (distichiasis, trichiasis, or ectopic cilia); secondary to exposure of the cornea (lagophthalmos or facial nerve paralysis); or immune mediated (eg, chronic superficial keratitis [ie, pannus]).2–4 Corneal pigmentation may develop as part of a wound-healing response after corneal trauma or with concurrent aqueous tear film deficiencies such as keratoconjunctivitis sicca.5,6

Corneal pigmentation is also known as corneal melanosis or pigmentary keratitis.7 The term corneal melanosis should only be used to indicate conditions in which corneal pigment has been histologically identified as melanin because other compounds can cause pigmented opacities in corneas. Iron, adrenochromes, and hemochromes can also cause pigmented corneal opacities.1,8,9 Pigmentary keratitis is a nonspecific diagnosis that is frequently made for animals evaluated in a clinical setting, including animals in which an inflammatory component of disease has not been definitively identified. Corneal pigmentation is a clinical sign, not a diagnosis, and its presence should prompt thorough ocular examination to identify comorbid conditions.

Two of the authors (ALL and REH) of the study reported here have frequently detected CP in Pugs evaluated at the University of Illinois Veterinary Teaching Hospital. Information in a CERF report10 indicates that 21.26% of Pugs that underwent CERF ophthalmic examinations during 2000 through 2008 had exposure keratopathy syndrome and pigmentary keratitis. Corneal pigmentation was identified in 47 of 74 (64%) Pugs evaluated by personnel of the University of Illinois Veterinary Teaching Hospital Comparative Ophthalmology Service from 2005 through 2010 (unpublished data). Because of this seemingly high prevalence of CP in Pugs evaluated in our hospital and the disparity between the authors' clinical impression of the prevalence and published10 CERF data, we conducted the study reported here. Although CP has been detected in Pugs with keratoconjunctivitis sicca,6 corneal squamous cell carcinoma,11 and ocular toxoplasmosis,12 CP has not been reported for Pugs without those conditions, to the authors' knowledge.

The purpose of the study reported here was to determine characteristics of CP in Pugs, identify risk factors associated with development of CP in Pugs, and estimate the prevalence of CP in Pugs. The hypotheses were that CP would have a high prevalence in Pugs and that risk factors for the development of CP in Pugs would be identified.

Materials and Methods

Animals—All study procedures were performed in compliance with the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research13 and were approved by the Institutional Animal Care and Use Committee of the University of Illinois. Informed, written consent was obtained from the owner of each Pug enrolled in the study. Pugs that were prospectively enrolled in the study were examined at 1 of 3 locations: a national dog show in Warwick, RI; a social dog event in Milwaukee; or a social dog event in Urbana, Ill. Pugs examined in Rhode Island were recruited on a first-come, first-served basis from the population of Pugs participating in the dog show. Newspaper and online publicity were used to solicit owners for the study in Wisconsin and Illinois. Eye examinations of Pugs enrolled in this study were performed free of charge. Pugs that were current or previous patients of the University of Illinois Veterinary Teaching Hospital were not eligible for enrollment in the study.

Data collection—Histories of Pugs included in the study were obtained by use of owner-completed questionnaires prior to examination of the dogs; information obtained included use of ocular medications (lubricant, lacrimostimulant, corticosteroid, or other medications), owner assessment of whether Pugs had clinically normal vision (yes vs no), previously diagnosed ocular disease (yes vs no), and clinical signs of ocular disease (yes vs no). Signalment (age, sex, and coat color) was recorded for each Pug. Only Pugs with fawn or black coat colors were eligible for inclusion in the study because other coat colors are not considered part of the breed standard by the AKC.14 Pugs were classified as AKC-registered or non–AKC-registered dogs. Pugs that were AKC-registered but had never entered a conformation competition at an AKC dog show were classified as non–AKC-registered in this study. Therefore, Pugs classified as AKC-registered dogs in this study had competed in conformation or agility and rally competitions, and non–AKC-registered Pugs were pet dogs that had not been entered in a performance competition.

For each Pug, digital photographsa of each eye and the head from the front and 1 side were obtained. Then, STTsb were performed for right and left eyes of each Pug. Corneal sensitivity of Pugs was assessed via corneal aesthesiometry; the axial aspect of each cornea was touched with a 4.0-cm nylon filamentc; the filament was shortened in 0.5-cm increments, and aesthesiometry was repeated when 3 touches did not elicit a positive response.15 A positive response was defined as a brisk blink in response to 2 of 3 filament touches. Tear film breakup timed was assessed via a previously described method by means of application of fluorescein stain to the corneal surface.16 Fluorescein stain was then rinsed from the cornea, fluorescein uptake was assessed, and results were recorded. Slit-lamp biomicroscopyf of the anterior segment each eye was then performed. Craniofacial conformation was examined and scored.e All examinations of Pugs were performed by one of the authors (ALL). The severity of CP for each eye of each Pug was graded by that same author (Figures 1–5). Corneal pigmentation was determined to be absent, very mild (< 2-mm diameter CP originating at the nasal aspect of the corneal limbus), mild (< 25% of the corneal surface affected), moderate (25% to 50% of the corneal surface affected), or severe (> 50% of the corneal surface affected). Other ophthalmic examination variables were graded by use of scoring systems (Appendix 1).

Figure 1—
Figure 1—

Photograph of a representative eye of a Pug with a transparent cornea and marked corneal limbus pigmentation. This appearance was considered representative of a clinically normal cornea.

Citation: Journal of the American Veterinary Medical Association 243, 5; 10.2460/javma.243.5.667

Figure 2—
Figure 2—

Photograph of a representative eye of a Pug with mild CP extending 2 to 3 mm from the nasal aspect of the corneal limbus toward the center of the cornea. This appearance was considered representative of very mild CP.

Citation: Journal of the American Veterinary Medical Association 243, 5; 10.2460/javma.243.5.667

Figure 3—
Figure 3—

Photograph of a representative eye of a Pug with CP in < 25% of the cornea extending from the nasal aspect of the corneal limbus toward the center of the cornea. This appearance was considered representative of mild CP.

Citation: Journal of the American Veterinary Medical Association 243, 5; 10.2460/javma.243.5.667

Figure 4—
Figure 4—

Photograph of a representative eye of a Pug with CP in 25% to 50% of the cornea extending from the nasal aspect of the corneal limbus toward the center of the cornea. This appearance was considered representative of moderate CP.

Citation: Journal of the American Veterinary Medical Association 243, 5; 10.2460/javma.243.5.667

Figure 5—
Figure 5—

Photograph of a representative eye of a Pug with severe, diffuse CP in > 50% of the cornea that precludes examination of intraocular structures. This appearance was considered representative of severe CP.

Citation: Journal of the American Veterinary Medical Association 243, 5; 10.2460/javma.243.5.667

Statistical analysis—Descriptive statistics were determined for all continuous variables.g Normality of data was assessed with the Shapiro-Wilk test. Comparisons of continuous variables for the group of Pugs with CP and the group of Pugs without CP were performed via ANOVA and the Kruskal-Wallis test (for determination of differences among Pugs in each group) and via the t test and Mann-Whitney U test (for determination of differences between groups) for normally and nonnormally distributed data, respectively. Bonferroni corrections were performed for analyses with multiple comparisons. Linear regression models were built to predict the values of continuous variables (STT, TFBUT, and CTT) by use of CP severity scores (Appendix 2). Scoring of categorical variables was determined with predetermined criteria (Appendix 1). Prevalence proportions and 95% confidence intervals were determined for various variables of Pugs. A χ2 or Fisher exact test was used to compare data regarding the presence or absence of clinical signs and the presence and severity of CP in the right eyes, left eyes, and both eyes of Pugs. Logistic regression was performed for 3 predictor variables that had Fisher exact test values of P < 0.1 (sex, AKC registration status, and owner assessment of vision of Pugs) to determine whether these variables were significantly associated with detection of CP in eyes of Pugs. The Hosmer-Lemeshow goodness-of-fit test was used to evaluate the fit of data regression models. A stepwise approach was used to build regression models. Values of P < 0.05 were considered significant. All analyses were performed with statistical software.h

Results

Two hundred ninety-five Pugs were included in the study. These dogs included 75 sexually intact females (25.4%; 95% CI, 20.8% to 30.7%), 69 sexually intact males (23.4%; 95% CI, 18.9% to 28.5%), 84 spayed females (28.5%; 95% CI, 23.6% to 33.9%), and 66 neutered males (22.4%; 95% CI, 17.9% to 27.5%); sex was not recorded for 1 dog (0.3%; 95% CI, 0% to 1.9%). Two hundred thirty-six Pugs (80.0%; 95% CI, 75.1% to 84.1%) had a fawn coat color, and 59 (20.0%; 95% CI, 15.8% to 24.9%) had a black coat color. The median age of the dogs was 4.1 years (interquartile range, 4.1 to 7.0 years; range, 0.25 to 18.9 years). One hundred thirty Pugs (44.1%; 95% CI, 38.5% to 49.8%) were AKC-registered dogs, and 165 (55.9%; 95% CI, 50.2% to 61.5%) were non–AKC-registered dogs. Results of ophthalmic diagnostic tests were summarized (Table 1). Corneal pigmentation had previously been diagnosed for 27 (9.2%; 95% CI, 6.4% to 12.9%) Pugs; 47 (15.9%; 95% CI, 12.2% to 20.5%) Pugs were treated topically with ocular medications at the time of data collection.

Table 1—

Results of ophthalmic tests performed for 295 Pugs evaluated to detect CP.

Right eyesLeft eyes
MedianIQRRangeMedianIQRRange
STT (mm/min)2220–250–332321–260–35
TFBUT (s)87–100–1696.5–110–23
CTT (cm)10.5–1.50–510.5–1.50–5

CTT = Corneal touch threshold. IQR = Interquartile range.

Corneal pigmentation was detected in at least 1 eye of 243 (82.4%; 95% CI, 77.6% to 86.3%) Pugs. Corneal pigmentation was detected in the left eyes of 232 (78.6%; 95% CI, 73.6% to 82.9%) Pugs and in the right eyes of 235 (79.7%; 95% CI, 74.6% to 84.1%) Pugs; these values were not significantly different. Corneal pigmentation had an appearance of brown opacification of corneas and originated from the nasal aspect of the corneal limbus and extended into the axial aspect of the cornea of each affected eye. Various amounts of corneal fibrosis and corneal vascularization were detected in eyes with CP. Of the 232 Pugs with CP in the left eye, 125 (53.9%; 95% CI, 47.2% to 60.4%) did not have associated corneal vascularization; of the 235 Pugs with CP in the right eye, 126 (53.6%; 95% CI, 47.7% to 60.8%) did not have associated corneal vascularization. The severity of CP, but not the presence of CP, was significantly (P < 0.001) associated with the presence and severity of corneal vascularization in left and right eyes; corneas with mild CP had had a lower severity of corneal vascularization versus corneas with severe CP.

Of the 232 affected left eyes, CP was very mild for 73 (31.5%), mild for 111 (47.8%), moderate for 26 (11.2%), and severe for 22 (9.5%). Of the 235 affected right eyes, CP was very mild for 73 (31.1%), mild for 105 (44.7%), moderate for 32 (13.6%), and severe for 25 (10.6%).

Detection of CP was not significantly associated with the evaluated signalment, history, or examination variables (Tables 2 and 3). Detection of CP was significantly associated with sex (P = 0.001; significantly fewer spayed females were affected vs Pugs of other sexes) and characteristics of ocular discharge (P = 0.003 for the left eyes and P = 0.004 for the right eyes; a significantly higher number of Pugs with CP had serous ocular discharge versus unaffected Pugs). Detection of CP in either eye was significantly (P = 0.03) associated with AKC registration status, with a smaller percentage of non–AKC-registered Pugs affected (n = 130 [78.8%]) than AKC-registered Pugs (113 [87.6%]); however, a diagnosis of CP for the left eyes (P = 0.051) or right eyes (P = 0.084) was not significantly associated with AKC registration status. Logistic regression models that included the variables sex, AKC registration status, and owner assessment of vision were significant (P = 0.001) predictors of the presence of CP in eyes of Pugs. Sex and AKC registration status of Pugs were significant coefficients in the final regression model. Spayed female Pugs were 3.69 (95% CI, 1.5 to 9.2; P = 0.004) times as likely to not have CP as were sexually intact female Pugs; no significant differences were detected for other comparisons of sex regarding the ORs for detection of CP.

Table 2—

Signalment and medical history variables not significantly associated with a diagnosis of CP in either eye of 295 Pugs evaluated to detect that condition.

VariableP value
Coat color0.551
Age0.436
Treatment with ocular medications0.526
Owner assessment of vision0.064
Previous diagnosis of ocular disease0.571
Owner-reported clinical signs0.220

The P values were determined with χ2 or Fisher exact tests. Values of P < 0.05 are considered significant.

Table 3—

Ophthalmic examination variables not significantly associated with a diagnosis of CP in left and right eyes of 295 Pugs evaluated to detect that condition.

VariableP value for CP in right eyesP value for CP in left eyes
Palpebral reflex1.0001.000
Presence of ocular discharge0.1820.198
Quantity of ocular discharge0.1830.216
Presence of upper eyelid entropion0.6590.674
Severity of upper eyelid entropion0.7860.777
Presence of lower eyelid entropion0.1920.199
Severity of lower eyelid entropion0.3370.588
Presence of distichia0.4880.449
Amount of distichia0.4210.495
Characteristics of distichia0.3250.143
Presence of ectopic cilia0.6530.642
Characteristics of ectopic cilia
Presence of eyelid margin defectsNDND
Presence of eyelid masses0.3420.328
Contact of the nasal fold with the cornea0.5390.376
Presence of corneal ulceration0.6530.487
Presence of corneal facet0.6540.582
Presence of scleral show* at nasal aspect of eye0.4670.565
Amount of scleral show* at nasal aspect of eye0.9510.585
Presence of scleral show* at temporal aspect of eye0.5880.472
Amount of scleral show* at temporal aspect of eye0.9000.958
Presence of iris hypoplasia0.8870.897
Presence of PPMs0.5530.397

The P values were determined with χ2 or Fisher exact tests.

Values of P < 0.05 are considered significant.

Scleral show was defined as an observed amount of visible sclera greater than a clinically normal observed amount of visible sclera.

— = Not determined because all ectopic cilia were subconjunctival. ND = Not determined because no eyelid margin defects were detected in Pugs of the study.

The severity of CP was not significantly (P = 0.052 for left eyes; P = 0.071 for right eyes) associated with AKC registration status. The severity of CP was significantly (P = 0.016 for left eyes; P = 0.037 for right eyes) associated with the coat color of Pugs; a significantly higher number of Pugs with a fawn coat color had moderate CP versus Pugs with a black coat color, and a significantly higher number of Pugs with a black coat color had mild CP versus Pugs with a fawn coat color. The severity of CP was significantly (P = 0.017 for left eyes; P = 0.013 for right eyes) associated with the sex of Pugs; a significantly higher number of female Pugs had no CP, very mild CP, or mild CP versus male Pugs and a significantly higher number of male Pugs had moderate or severe CP versus female Pugs. The associations of ophthalmic diagnostic test values with CP scores were summarized (Table 4). Although the presence of CP was not significantly associated with STT or TFBUT values, values of STT and TFBUT were significantly lower for Pugs with severe CP versus those with moderate CP in left and right eyes, and values of CTT were significantly higher for Pugs with severe CP versus those with moderate CP in right eyes. Results of a linear regression model were significant for each continuous variable for each eye, although regression models accounted for ≤ 13% of the variation in values of the continuous variables.

Table 4—

Results of linear regression indicating associations of ophthalmic diagnostic test values with CP scores for 295 Pugs.

Ophthalmic diagnostic test
CP score comparisonSTTTFBUTCTT
Left eyes
0 vs 10.5840.1770.027
1 vs 20.0370.4930.204
2 vs 30.3680.2500.110
3 vs 40.001< 0.0010.027
Right eyes
0 vs 10.5150.2140.082
1 vs 20.3470.1450.905
2 vs 30.100.0140.479
3 vs 40.004< 0.0010.005

Data are P values. Values of P ≤ 0.05 are considered significant.

See Table 1 for remainder of key.

Two hundred seventy-two Pugs were examined to detect iris hypoplasia (Figure 6) and PPMs (Figure 7). Information regarding those problems was not recorded for the first 23 Pugs included in the study; information regarding iris hypoplasia and PPMs were recorded for dogs that were subsequently included in the study because those problems were detected in some of the first 23 dogs that were examined. Of these 272 Pugs, 193 (71.0%; 95% CI, 65.3% to 76.0%) had iris hypoplasia in the left eye and 196 (72.1%; 95% CI, 66.5% to 77.1%) had iris hypoplasia in the right eye. Of these 272 Pugs, 228 (83.8%; 95% CI, 78.9% to 87.7%) had iris-to-iris PPM in the left eye and 232 (85.3%; 95% CI, 80.6% to 89.0%) had that problem in the right eye. A diagnosis of iris hypoplasia or PPM was not significantly associated with the presence or severity of CP (Table 2). A diagnosis of iris hypoplasia was not significantly (P = 0.881 for left eyes; P = 0.615 for right eyes) associated with a diagnosis of PPM. Only 1 Pug in this study (a 6-year-old spayed female non–AKC-registered dog) did not have CP, iris hypoplasia, or PPM.

Figure 6—
Figure 6—

Photograph of a representative eye of a Pug with iris hypoplasia. Notice the diamond- to wedge-shaped discontinuities in the anterior surface of the iris.

Citation: Journal of the American Veterinary Medical Association 243, 5; 10.2460/javma.243.5.667

Figure 7—
Figure 7—

Photograph of a representative eye of a Pug with PPMs. Notice the multifocal strand-shaped iris-to-iris PPMs and areas of mild hypoplasia (oval-shaped discontinuities) on the anterior surface of the iris.

Citation: Journal of the American Veterinary Medical Association 243, 5; 10.2460/javma.243.5.667

Discussion

To the authors' knowledge, this is the first study in which CP has been documented for a large number of Pugs. On the basis of the results of this study, PK may be an appropriate term for this condition. Results of the study suggested that this condition is different than other reported causes of CP because CP in Pugs was not associated with diseases such as tear film deficiencies or ocular adnexal abnormalities. We defined PK as pigmentation of the cornea that originated from the nasal aspect of the corneal limbus with various amounts of corneal fibrosis and vascularization. Although we expect that this condition is progressive, the rate of progression may be variable; progression of this condition was not evaluated in the present study. Results of this study suggested that tear production is not decreased during the early stages of the disease in Pugs.

The results of this study suggested that PK may have high prevalence in Pugs in the United States. Although a significant difference in the prevalence of this condition in AKC-registered (87.6%) and non–AKC-registered Pugs (78.8%) was detected in this study, that difference did not seem to be clinically important because the overall prevalence of the condition in Pugs was high. This finding of a high prevalence suggested there may be a genetic basis for PK in Pugs. We considered it unlikely that this high prevalence was attributable to the breeding of dogs in a single kennel or from a single ancestor; therefore, the condition seemed to be a problem of the Pug breed.

Pigmentation of the cornea is a nonspecific biological response to various stimuli, including mechanical abrasion, immune-mediated keratitis, trauma, and tear film disorders. Other authors7,17 suggested that eyelid conformation and tear film quality are major contributors to the pathogenesis of CP in brachycephalic dogs. The results of the present study suggested that these factors may not cause PK in Pugs. No significant differences in the severity of lagophthalmos, entropion, or reflex tear production were detected between Pugs with CP and those without CP in this study. Although Pugs with severe CP had low reflex tear production and high TFBUT, Pugs with very mild, mild, or moderate CP did not have significantly lower reflex tear production or higher TFBUT, compared with Pugs without CP. This finding suggested that low reflex tear production and high TFBUT may have been caused by chronic corneal disease and were likely not the cause of such disease. Pugs of the present study had a median STT value that was similar to previously published values for dogs of other breeds, but TFBUT and CTT values in these Pugs were lower than previously published values of those variables for mesaticephalic breeds and were consistent with values for brachycephalic breeds.15,16 Pigmentary keratopathy in Pugs may be a genetic disease, the severity of which may be modified or exacerbated by comorbid conditions such as entropion, low tear production, or corneal trauma, rather than a disease caused by adnexal conformational or tear-quality abnormalities.

Approximately half of the Pugs with CP in the present study did not have vascularization of the cornea. Corneal pigmentation is typically caused by chronic superficial keratitis or keratoconjunctivitis sicca in dogs of other breeds, and corneal vascularization is frequently associated with CP in such dogs.3,5 The finding of the present study that Pugs had CP, which originated in the nasal aspect of the corneal limbus without corneal vascularization, suggested that pigment production by local cells may have caused CP rather than hematogenous delivery of melanocytes from distant sites. Results of another study18 indicate that limbal melanocytes migrate into corneal wounds and cause CP. For a Pug of another study6 that had clinical signs consistent with the PK condition identified in Pugs of the present study, results of histologic examination indicated corneal opacity was likely caused by melanin. The corneal pigment in Pugs of the present study may have been melanin, and CP in these dogs may have been caused by an abnormality in function or a low number of limbal stem cells or melanocytes. Histologic examination of corneas of Pugs with this condition is warranted to identify the corneal pigment. Such a study should be performed prospectively and include Pugs that have undergone complete ophthalmic examination to exclude other causes of CP.

The importance of the association between sex of Pugs and detection of CP was not determined in this study. That finding of this study may have been attributable to hormonal influences on the presence or severity of CP in Pugs. Further investigation is warranted to determine the importance of this finding.

The prevalence of CP was significantly higher for Pugs of the present study than it is for dogs with information in the CERF database.10 This difference in prevalence of CP may be attributable to the older ages of Pugs at the time of ocular examination in the present study versus other dogs with information in the CERF database. Breeders typically bring litters of puppies to veterinarians for CERF examination prior to the sale or transfer to another owner, which may falsely decrease the prevalence of CP in dogs because young dogs may not have clinical signs of the condition. The biological progression of PK in Pugs is unknown, and further studies are warranted to determine characteristics of progression of the disease.

The high prevalence of iris hypoplasia and iris to iris PPM in Pugs of the present study was an unexpected finding. No significant association was detected between a diagnosis of iris hypoplasia and detection of PPM or CP in Pugs of this study. Iris hypoplasia or PPM status was not recorded for the first 23 Pugs evaluated in this study because we did not originally plan to include such information; such information was recorded after those conditions were detected in Pugs early during the study. The clinical importance of this finding is unknown, to the authors' knowledge. The PK condition identified in Pugs of the present study may be part of a syndrome of anterior segment dysgenesis. Further studies are warranted to determine the associations among PK, iris hypoplasia, and PPM in Pugs.

Treatment of Pugs with CP is poorly described in peer-reviewed literature. We routinely treat Pugs with CP via topical administration of immunomodulator drugs such as cyclosporine A or tacrolimus. Corticosteroids may also be useful for reducing the severity of CP in Pugs, but such drugs may impair corneal wound healing in dogs with corneal ulceration.3 Dogs that have CP and extreme lagophthalmos or large palpebral fissures may be surgically treated with medial canthoplasty.2 Further studies are warranted to determine the efficacy of such treatments for Pugs with PK.

Characteristics of PK in Pugs were identified in this study, and results suggested that this condition may have high prevalence in that breed. Further studies are warranted to determine the pathogenesis of PK in Pugs and to develop effective treatments for the condition.

ABBREVIATIONS

AKC

American Kennel Club

CERF

Canine Eye Registry Foundation

CP

Corneal pigmentation

PK

Pigmentary keratopathy

PPM

Persistent pupillary membrane

STT

Schirmer tear test

TFBUT

Tear film breakup time

a.

Nikon D200, Nikon Inc, Melville, NY.

b.

STT, Schering-Plough Animal Health, Union, NJ.

c.

Luneau Cochet-Bonnet Corneal Aesthesiometer, Wilson Ophthalmic, Mustang, Okla.

d.

BioGlo Fluorescein Sodium Ophthalmic Strips USP, Ocularvision Inc, Solvang, Calif.

e.

Finoff Transilluminator, Welch-Allyn, Skaneateles, NY.

f.

Keeler PSL Classic, Keeler Instruments Inc, Broomall, Pa.

g.

IBM SPSS Statistics, version 20.0, IBM Inc, Chicago, Ill.

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Appendix 1

Scores assigned for various ophthalmic examination variables for right and left eyes of 295 Pugs evaluated to detect CP.

VariableScoring system
Menace response1 = positive; 2 = inconsistent; 3 = absent
Dazzle reflex1 = positive; 2 = inconsistent; 3 = absent
Direct pupillary light reflex1 = positive; 2 = slow or incomplete; 3 = absent
Consensual pupillary light reflex1 = positive; 2 = slow or incomplete; 3 = absent
Palpebral reflex1 = positive; 2 = inconsistent; 3 = absent
Presence of ocular discharge1 = present; 2 = absent
Characteristics of ocular discharge0 = none; 1 = serous; 2 = mucoid; 3 = serous to mucoid; 4 = mucopurulent
Amount of ocular discharge1 = mild (thread of material in the palpebral fissure); 2 = moderate (plaque of material accumulated in the palpebral fissure or on the face of the dog); 3 = severe (discharge dried on face of the dog)
Presence of upper eyelid entropion1 = present; 2 = absent
Severity of upper eyelid entropion0 = absent; 1 = mild; 2 = moderate; 3 = severe
Presence of lower eyelid entropion1 = present; 2 = absent
Severity of lower eyelid entropion0 = absent; 1 = mild (< 25% of the length of the eyelid margin); 2 = moderate (25% to 50% of the length of the eyelid margin); 3 = severe (> 50% of the length of the eyelid margin)
Presence of distichia1 = present; 2 = absent
Amount of distichia1 = mild (< 3 hairs/eyelid); 2 = moderate (3–6 hairs/eyelid); 3 = severe (> 6 hairs/eyelid)
Characteristics of distichia1 = coarse; 2 = fine
Presence of ectopic cilia1 = present; 2 = absent
Characteristics of ectopic cilia1 = erupted through the palpebral conjunctiva; 2 = subconjunctival
Presence of eyelid margin defects1 = present; 2 = absent
Presence of eyelid masses1 = present; 2 = absent
Eyelid mass has appearance of a meibomian gland adenoma1 = yes; 2 = other
Eyelid mass contacts the cornea1 = yes; 2 = no
Nasal fold contacts the cornea1 = constant; 2 = inconsistent; 3 = does not contact the cornea
Presence of CP1 = yes; 2 = no
Severity of CP0 = none; 1 = very mild (< 2-mm diameter of pigment extending in an arc from the nasal aspect of the corneal limbus); 2 = mild (< 25% of the cornea affected); 3 = moderate (25% to 50% of the cornea affected); 4 = severe (> 50% of the cornea affected)
Presence of corneal vascularization1 = yes; 2 = no
Severity of corneal vascularization1 = none; 2 = mild (< 25% of the corneal surface affected); 3 = moderate (25% to
50% of the corneal surface affected); 4 = severe (> 50% of the corneal surface affected)
Presence of corneal fibrosis1 = yes; 2 = no
Severity of corneal fibrosis1 = none; 2 = mild (< 25% of the corneal surface affected); 3 = moderate (25% to 50% of the corneal surface affected); 4 = severe (> 50% of the corneal surface affected)
Presence of corneal ulceration1 = present; 2 = absent
Severity of corneal ulceration1 = superficial (only loss of epithelium); 2 = anterior stroma (loss of < 50% of the
corneal stroma); 3 = deep (loss of > 50% of the corneal stroma)
Presence of corneal facet1 = present; 2 = absent
Presence of scleral show* at nasal aspect of eye1 = yes; 2 = no
Severity of scleral show* at nasal aspect of eye1 = none; 2 = mild (< 2 mm of sclera exposed); 3 = moderate (2–4 mm of sclera
exposed); 4 = severe (> 4 mm sclera exposed)
Presence of scleral show* at temporal aspect of eye1 = yes; 2 = no
Severity of scleral show* at temporal aspect of eye1 = none; 2 = mild (< 2 mm of sclera exposed); 3 = moderate (2–4 mm of sclera exposed); 4 = severe (> 4 mm sclera exposed)
Presence of iris hypoplasia1 = yes; 2 = no; 3 = not recorded
Presence of PPM1 = yes; 2 = no; 3 = not recorded

Scleral show was defined as an observed amount of visible sclera greater than a clinically normal observed amount of visible sclera.

Appendix 2

Linear regression models built to predict the values of ophthalmic diagnostic test variables (STT, TFBUT, and CTT) on the basis of CP severity scores.

Linear regression equationR2FP value
Left eye
 STT (mm/min) = 25.005 – (1.709 × CP score OS)0.08325.886< 0.001
 TFBUT (sec) = 10.423 – (1.11 × CP score OS)0.13743.498< 0.001
 CTT (cm) = 1.186 – (0.140 × CP score OS)0.05115.415< 0.001
Right eye
 STT (mm/min) = 24.106 – (1.321 × CP score OD)0.13243.497< 0.001
 TFBUT (sec) = 10.032 – (1.148 × CP score OD)0.19263.223< 0.001
 CTT (cm) = 1.136 – (0.139 × CP score OD)0.05416.417< 0.001
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