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Evaluation of diabetes mellitus regulation in dogs treated with ophthalmic preparations of prednisolone acetate versus diclofenac sodium

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  • 1 1Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.
  • | 2 2Department of Statistics, Department of Arts and Sciences, Kansas State University, Manhattan, KS 66506.

Abstract

OBJECTIVE

To evaluate and compare regulation of diabetes mellitus (DM) in dogs with cataracts and well-controlled DM that received an ophthalmic preparation of prednisolone acetate versus diclofenac sodium.

ANIMALS

22 client-owned dogs with cataracts and well-controlled DM.

PROCEDURES

A prospective, randomized, double-masked, experimental study was conducted. On days 0 and 32, serum fructosamine concentrations (SFCs), clinical scores, and body weights were determined. Dogs were assigned to receive a topically administered ophthalmic preparation of either prednisolone acetate 1% or diclofenac sodium 0.1% in each eye 4 times daily for 28 days. Data analysis was conducted with generalized linear mixed models.

RESULTS

Findings indicated no meaningful differences in SFCs, clinical scores, or body weights between the treatment groups on days 0 or 32. Clinical score on day 0 was positively associated with SFC, as indicated by the corresponding rate of change such that each 1 -unit increase in clinical score was associated with an approximately 45.6 ± 9.4 μmol/L increase in SFC. In addition, the least squares mean ± SEM SFC was higher in spayed females (539.20 ± 19.23 μmol/L; n = 12) than in castrated males (458.83 ± 23.70 μmol/L; 8) but did not substantially differ between sexually intact males (446.27 ± 49.72 μmol/L; 2) and spayed females or castrated males regardless of the treatment group assigned.

CONCLUSIONS AND CLINICAL RELEVANCE

Findings indicated no evidence for any differential effect on DM regulation (assessed on the basis of SFCs, clinical scores, and body weights) in dogs treated topically with an ophthalmic preparation of prednisolone versus an ophthalmic preparation of diclofenac. Additional research investigating plasma concentrations of topically applied ophthalmic glucocorticoid medications is warranted. (Am J Vet Res 2019;80:1129-1135)

Abstract

OBJECTIVE

To evaluate and compare regulation of diabetes mellitus (DM) in dogs with cataracts and well-controlled DM that received an ophthalmic preparation of prednisolone acetate versus diclofenac sodium.

ANIMALS

22 client-owned dogs with cataracts and well-controlled DM.

PROCEDURES

A prospective, randomized, double-masked, experimental study was conducted. On days 0 and 32, serum fructosamine concentrations (SFCs), clinical scores, and body weights were determined. Dogs were assigned to receive a topically administered ophthalmic preparation of either prednisolone acetate 1% or diclofenac sodium 0.1% in each eye 4 times daily for 28 days. Data analysis was conducted with generalized linear mixed models.

RESULTS

Findings indicated no meaningful differences in SFCs, clinical scores, or body weights between the treatment groups on days 0 or 32. Clinical score on day 0 was positively associated with SFC, as indicated by the corresponding rate of change such that each 1 -unit increase in clinical score was associated with an approximately 45.6 ± 9.4 μmol/L increase in SFC. In addition, the least squares mean ± SEM SFC was higher in spayed females (539.20 ± 19.23 μmol/L; n = 12) than in castrated males (458.83 ± 23.70 μmol/L; 8) but did not substantially differ between sexually intact males (446.27 ± 49.72 μmol/L; 2) and spayed females or castrated males regardless of the treatment group assigned.

CONCLUSIONS AND CLINICAL RELEVANCE

Findings indicated no evidence for any differential effect on DM regulation (assessed on the basis of SFCs, clinical scores, and body weights) in dogs treated topically with an ophthalmic preparation of prednisolone versus an ophthalmic preparation of diclofenac. Additional research investigating plasma concentrations of topically applied ophthalmic glucocorticoid medications is warranted. (Am J Vet Res 2019;80:1129-1135)

Diabetes mellitus is a common endocrinopathy in dogs, with reported prevalence ranging from 1 in 100 to 1 in 500 dogs affected.1 The cause of DM in dogs is multifactorial, and studies2–5 suggest that genetics, environmental factors, and immune-mediated components contribute to the development of the disease. Epidemiological studies1,4,6 show that age of onset for most affected dogs is between 4 and 15 years and that female dogs have an increased risk of developing DM. Genetic predispositions have been suggested, but the mode of inheritance or specific genes involved have not been identified in most breeds. In addition, most dogs with DM are insulin dependent, resembling type 1 diabetes in humans.6

Cataract formation is the most frequently occurring and important ocular complication associated with DM in dogs, and such cataracts often have an acute onset, are bilaterally symmetric, and rapidly progress. A retrospective cohort study7 of dogs with DM shows that most (89/200 [44.5%]) dogs develop cataracts within 5 to 6 months after DM is diagnosed. Serum glucose and sorbitol concentrations, duration of hyperglycemia, and aldose reductase activity are thought to contribute to the development of cataracts in patients with diabetes.6,8-10

Leakage of soluble lens proteins through the intact capsule of a cataractous lens triggers LIU.11–13 The pathogenesis of LIU is not completely understood but is believed to be the result of a breakdown in the normal T-cell tolerance of lens proteins and other lens components.14 In a healthy eye, small amounts of lens protein leak across the intact lens capsule, which leads to low-dose immunologic T-cell tolerance.15,16 However, increased immune system exposure to lens proteins, either by leakage through the more permeable capsule of a cataractous lens or through a lens capsule rupture, may overwhelm this tolerance and incite a cell-mediated or humoral immune response, alone or in combination, and breakdown of the blood-aqueous barrier has been demonstrated and quantified by fluorophotometry in the eyes of dogs with all stages of cataract.17 In a retrospective study18 of dogs that were cataract surgery candidates, 82 of 116 (71%) dogs overall had LIU, whereas 23 of 25 (92%) dogs with DM had LIU. Furthermore, eyes with LIU may have lower long-term success rates following cataract surgery.11,18,19

Topical ophthalmic preparations of glucocorticoids and NSAIDs are most commonly used to control inflammation in the anterior segment of the eye.13 Such use includes treatment of LIU (clinical or subclinical) in dogs with DM and cataracts and preparing the eyes for cataract surgery. In our experience, patients with moderate to severe LIU are more likely prescribed a topical ophthalmic product containing a glucocorticoid, rather than an NSAID. In addition, most patients undergoing cataract surgery receive a topically administered anti-inflammatory medication for a minimum of 2 months after cataract surgery,20 with some patients receiving the medication indefinitely.

Glucocorticoids impair glucose homeostasis through several complex physiologic mechanisms and negatively impact glycemic control. For instance, glucocorticoids induce the gluconeogenic enzymes fructose-1,6-biphosphatase, glucose-6-phosphatase, and phosphoenopyruvate carboxykinase.21,22 Glucocorticoids also increase substrates for gluconeogenesis by stimulating proteolysis in skeletal muscle and lipolysis in adipose tissue, thereby increasing concentrations of blood glucose.23–25 Endogenous and exogenous systemic glucocorticoids can induce insulin resistance in animals with and without DM and can reduce glycogen synthesis by affecting glycogen synthase kinase-3 phosphorylation.26

A study27 of 130 dogs that underwent surgical treatment for cataracts shows that 66 (50.8%) dogs also had DM. Thus, if topically applied ophthalmic preparations of glucocorticoids could alter glycemic control in treated dogs, then the use of such medication after cataract surgery in dogs with DM may contribute to difficulty in regulating DM. Although it has been suggested that topical ophthalmic preparations of glucocorticoids might cause insulin antagonism and interfere with glycemic control in dogs with DM, especially in toy and miniature breeds,6 there are currently no published reports of investigations that have evaluated the effects of topically applied ophthalmic preparations of glucocorticoids on DM regulation in dogs.

The purpose of the prospective, randomized, double-masked study reported here was to evaluate and compare DM regulation in dogs with cataracts and well-controlled DM that received a topical ophthalmic preparation of prednisolone acetate 1.0% versus diclofenac sodium 0.1%. We hypothesized that regulation of DM in dogs would not meaningfully differ between dogs treated with an ophthalmic preparation of prednisolone and dogs treated with an ophthalmic preparation of diclofenac.

Materials and Methods

Animals

Client-owned dogs with naturally occurring, insulin-dependent DM and cataracts were eligible for the study. Dogs with poorly controlled DM, concurrent infections, uncontrolled hyperadrenocorticism, neoplasia, moderate to severe LIU, corneal ulceration, glaucoma, keratoconjunctivitis sicca, or a history of receiving topical or systemic anti-inflammatory medications within the past month were excluded from the study. Owners of eligible dogs were identified by clinicians in the ophthalmology, internal medicine, and general medicine departments; a search of the medical records; and solicitation on the Kansas State University College of Veterinary Medicine website. Whether a dog's DM was controlled or not was determined on the basis of findings from a complete physical examination (including consideration of medical history) performed by a board-certified internal medicine specialist (KSK or TS). Written informed consent was obtained from owners prior to their dogs’ enrollment, and the study was approved by the Kansas State University Institutional Animal Care and Use Committee. The study represented a continuation of a project reported in a thesisa and included data on 12 dogs from that thesis.

Evaluations

On days 0 and 32 after enrollment, each dog underwent complete physical (KSK or TS) and ophthalmic (AJR or JMM) examinations. Ophthalmic examination included Schirmer tear test I (ie, without anesthetic),b fluorescein staining,c rebound tonometery,d slit-lamp biomicroscopy,e and indirect ophthalmoscopyf (when cataracts did not preclude posterior segment examination). In addition, on days 0 and 32, a clinical score was determined by a veterinary internal medicine specialist (KSK or TS) who assigned a point value to each binary outcome used to assess control of DM (Appendix). Higher clinical scores meant poorer glycemic control. Also, on both of these days, body weight was measured and a CBC, biochemical analyses with SFC, and urinalysis were performed. Each dog was then hospitalized for up to 3 days for glucose concentration monitoring with a CGMS.g Hospitalization was necessary to ensure accurate calibration of the monitoring system twice daily. While hospitalized, dogs received the same insulin treatment (product, dose, and frequency) and meals (product, amount, and timing) as they received routinely at home. The regulation of DM was assessed with SFCs, clinical scores, blood glucose concentrations as measured with CGMSs, and changes in body weight.

Use of CGMSs

Each CGMS consisted of a monitor, sensor that was placed under the skin, and transmitter that wirelessly sent data to the monitor. The CGMS estimated blood glucose concentrations through a reaction that converted local interstitial fluid glucose into gluconic acid and hydrogen peroxide and created an electric current, for which the CGMS then recorded a corresponding blood glucose concentration. The CGMS could record glucose concentrations between 40 and 400 mg/dL. The CGMS sensor was placed in the dorsal subcutaneous tissue of the thorax, approximately 1 to 3 inches lateral to the dorsal midline. To accomplish this, a small area of skin was shaved and then wiped with an alcohol swab prior to placement. The CGMS sensor was inserted into the skin, and after the stylet was removed, the sensor was fastened to the skin with cyanoacrylate adhesive or elastic adhesive tape. The CGMS recording device was then attached to the dog's halter or cage door. The manufacturer's instructions were followed for initialization and calibration.

Treatment

With a randomized block design by sex, age, and body weight, dogs were assigned to receive an ophthalmic preparation of either prednisoloneh (prednisolone treatment group) or diclofenaci (diclofenac treatment group). The medications were dispensed in identical bottles and were labeled drug red or drug blue so that the owners and investigators were masked to the identity of the medication. Owners were instructed to administer 1 drop of the assigned medication to each eye of their dogs 4 times daily for 4 weeks (days 4 to 32 of the study). The owners were also instructed to continue to administer insulin as directed twice daily. To minimize potential problems with poor compliance by owners, the owners were trained on how to administer the topical medication properly, given a medication administration log to complete, and contacted once a week during the study period to discuss the medication schedule.

Statistical analysis

A generalized linear mixed model was fitted to each response, namely SFC (μmol/L), body weight (kg), and clinical score (expressed in a log scale), assuming a normal conditional distribution of the response. The linear predictors included the fixed effects of the treatment (day of treatment [day 0 vs day 32] and 2-way interaction) and the random effect of the patient nested within treatment to properly recognize experimental units and repeated measures over time. Explanatory covariates for SFCs were sex of dogs and clinical scores at the time of enrollment. In addition, sex of dogs was considered as a covariate for body weight. Variance components were estimated with restricted maximum likelihood. The Kenward-Roger method was used to estimate degrees of freedom and make the corresponding adjustments when estimating the SE. The model was fitted by means of generalized linear mixed modeling.j Results of a power analysis indicated that a sample size of 18 dogs was required to grant 80% power to detect a 70-μmol/L difference in SFC, assuming a residual SD of SFC of 70 μmol/L, which was calculated on the basis of a previous study28 and considered reasonable. Estimated LSMs, corresponding estimated SEM, and 95% confidence intervals were reported. Relevant pairwise comparisons with Bonferroni adjustments were conducted to avoid inflation of type I error from multiple comparisons. Values of P ≤ 0.05 were considered significant.

Results

Animals

Twenty-two client-owned dogs, including 12 that were also included in an earlier study,a with naturally occurring, insulin-dependent DM and cataracts were enrolled in the present study. There were 12 spayed females, 8 castrated males, and 2 sexually intact males. There were 5 mixed-breed dogs; 3 each of Cairn Terrier, Miniature Schnauzer, and Rat Terrier; 2 Maltese; and 1 each of Australian Shepherd, Border Collie, Chesapeake Bay Retriever, Chihuahua, Pembroke Welsh Corgi, and Labrador Retriever. Collectively, the dogs had 4 incipient, 13 immature, 25 mature, and 2 hypermature cataracts. Ten dogs were assigned to the prednisolone treatment group, whereas 12 dogs were assigned to the diclofenac treatment group.

Age and body weight

The mean ± SD age was 8.7 ± 2.1 years (range, 6.0 to 13.1 years), and the mean ± SD body weights at days 0 and 32 were both 17.1 ± 11.7 kg. Age as a covariate was not included in the analysis because it did not show any indication of improving model fit to data. Model assumptions were evaluated with externally studentized residuals and were considered to be reasonably met. There were no meaningful differences in the LSM body weight between the treatment groups on either day 0 or day 32 (Table 1). Similarly, there were no meaningful changes in the LSM body weight from day 0 to day 32 in either treatment group.

Table 1—

Results of generalized linear mixed-model analysis of findings for variables assessed on day 0 (before treatment) and day 32 (28 days of treatment) to evaluate DM regulation in 22 dogs with cataracts and well-controlled DM that received a topical ophthalmic preparation of either prednisolone acetate 1% (prednisolone group; n = 10) or diclofenac sodium 0.1% (diclofenac group; 12) administered in each eye 4 times daily for 28 days.

 SFC (μmol/L)Clinical scoreBody weight (kg)
Treatment groups and daysLSM (95% CI)P valueLSM (95% CI)P valueLSM (95% CI)P value
Diclofenac group day 0 versus day 32 0.45 0.84 0.21
 Diclofenac group day 0463.39 (413.77–513.02) 1.54 (0.84–2.50) 18.82 (11.58–26.05) 
 Diclofenac group day 32481.64 (432.02–531.27) 1.43 (0.78–2.30) 19.04 (11.80–26.27) 
Prednisolone group day 0 versus day 32 0.19 0.54 0.10
 Prednisolone group day 0467.64 (404.55–530.73) 1.67 (0.91–2.73) 25.22 (15.64–34.80) 
 Prednisolone group day 32513.04 (449.95–576.13) 2.09 (1.16–3.41) 24.83 (15.25–34.41) 
Diclofenac group versus prednisolone group day 0 0.90 0.83 0.21
 Diclofenac group day 0463.39 (413.77–513.02) 1.54 (0.84–2.50) 18.82 (11.58–26.05) 
 Prednisolone group day 0467.64 (404.55–530.73) 1.67 (0.91–2.73) 25.22 (15.64–34.80) 
Diclofenac group versus prednisolone group day 32 0.38 0.31 0.26
 Diclofenac group day 32481.64 (432.02–531.27) 1.43 (0.78–2.30) 19.04 (11.80–26.27) 
 Prednisolone group day 32513.04 (449.95–576.13) 2.09 (1.16–3.41) 24.83 (15.25–34.41) 

CI = Confidence interval.

SFC

The LSM SFC did not differ significantly (P = 0.90 and P = 0.38, respectively) between the prednisolone and diclofenac treatment groups on day 0 (467.64 and 463.39 μmol/L, respectively) or day 32 (513.04 and 481.64 μmol/L, respectively). Similarly, the LSM SFC did not change substantially from day 0 to day 32 for either treatment group (Table 1). However, the LSM ± SEM of the SFC was significantly (P = 0.05) higher in spayed females (539.20 ± 19.23 μmol/L; n = 12), compared with castrated males (458.83 ± 23.70 μmol/L; 8), regardless of the treatment group assigned. The LSM SFC was approximately 80.4 ± 30.1 μmol/L higher in spayed females than in castrated males. The LSM ± SEM of the SFC in the sexually intact males (446.27 ± 49.72 μmol/L; n = 2) was not substantially different from that in the castrated males or spayed females because the SFC varied more in the sexually intact males, as indicated by the magnitude of the estimated SEM.

Clinical score

There was no evidence for any differential effect of treatment on clinical scores (Table 1). However, the LSM clinical score on day 0 was positively associated (P < 0.001) with SFC, as indicated by the corresponding rate of change such that each 1-unit increase in clinical score was associated with an approximately 45.6 ± 9.4 μmol/L increase in the SFC.

Discussion

Results of the present study indicated that there were no meaningful differences in SFCs, clinical scores, or body weights of dogs with cataracts and well-controlled DM that received topical ophthalmic preparations of prednisolone versus diclofenac administered 4 times daily to each eye for 4 weeks. However, the clinical score (higher score = poorer control of DM; lower score = better control of DM) was positively associated with SFC on day 0 for dogs of the present study. Fructosamines are formed by the irreversible binding of glucose to serum proteins, such that the SFC reflects the mean blood glucose concentration over the preceding 2 to 3 weeks.29 Serum fructosamine concentrations are not affected by day-to-day variations that affect serial blood glucose concentrations and have been recommended for assessing glycemic control in dogs with DM.30

Our findings also indicated that SFCs were approximately 80.4 ± 30.1 μmol/L higher in spayed females than in castrated males but did not differ substantially between sexually intact males and castrated males or between sexually intact males and spayed females. There were no sexually intact females in the present study.

The most common and substantial ocular manifestation of DM in dogs is cataract formation.8 Glucose is predominantly anaerobically metabolized with the hexose monophosphate (pentose) shunt, and the major end product is lactic acid. The rate of glycolysis is limited by inhibition of the hexokinase enzyme when glucose concentrations are high (> 175 mg/dL).31 When the concentration of glucose saturates the hexokinase enzyme in the glycolytic pathway, glucose is metabolized by aldose reductase into sorbitol through the polyol pathway.31 Sorbitol is subsequently converted by sorbitol dehydrogenase to fructose, which can slowly diffuse through the lens capsule or reenter the glycolytic pathway.32 However, sorbitol is produced faster than it can be converted to fructose in the lens.33 The polar nature of sorbitol prevents its intracellular removal through diffusion, which then leads to an accumulation of sorbitol within the lens.33 Sorbitol causes an osmotic gradient and water imbibition into the lens, which leads to lens fiber swelling and rupture, generation of free radicals and reactive oxygen species, vacuole formation, and cataract development.33–35 Because of high activity of lenticular aldose reductase, dogs with DM are more susceptible to cataract formation than are older cats with DM.32 Cataracts in dogs with DM typically begin as equatorial cortical vacuoles32,34 that may progress to 100% involvement of the lens, leading to blindness. In addition, cataracts in dogs with DM often progress rapidly and cause LIU,34 for which topical anti-inflammatory medications are indicated, with the drug type and dosage frequency selected on the basis of the severity of the clinical disease.

Following topical application of an ophthalmic medication, a portion of the medication will be absorbed systemically through both the conjunctiva and the nasal or oral mucosa, after the medication passes through the nasolacrimal system.36 Although serum concentrations of drugs that are applied topically to the eye are generally low, systemic adverse effects, such as suppression of the hypothalamic-hypophyseal-adrenal axis, adrenal suppression, and histopathologic hepatic changes in dogs after application of topical ophthalmic preparations of glucocorticoids, have been reported.37–39 In addition, a study40 of humans who underwent cataract surgery and applied an ophthalmic preparation of either dexamethasone or diclofenac to the affected eye 4 times daily shows that the blood glucose concentration in patients with diabetes treated with the dexamethasone preparation significantly increases over a 1-month treatment period and that the blood glucose concentration at the end of the treatment period is significantly higher in those patients than in patients with diabetes treated with the diclofenac preparation. In that same study,40 there were no meaningful differences in blood glucose concentrations for patients without diabetes treated with the dexamethasone versus the diclofenac ophthalmic preparation.40 Similarly, in humans with well-controlled type 2 DM (defined as an initial blood glucose concentration ≤ 135 mg/dL), topical application of an ophthalmic preparation of dexamethasone disodium phosphate 8 times/d for 7 days causes a notable increase in blood glucose concentrations, which return to pretreatment concentrations after discontinuation of the medication.41

In contrast, there was no evidence in the present study for any differential effect on glycemic control in dogs with DM treated topically with an ophthalmic preparation of prednisolone versus an ophthalmic preparation of diclofenac. Our results were consistent with findings in humans that show no meaningful differences in SFCs and mean blood glucose concentrations before versus after an intra-articular injection of methylprednisolone acetate (35 mg total) in the shoulder joint,42 no meaningful change in SFCs following an intra-articular injection of betamethasone into the knee joint,43 and no notable increase in hemoglobin A1c concentration after a posterior subtenon injection of triamcinolone acetonide (although some patients had fasting blood glucose concentrations above the reference limit).44

A major limitation of the present study was the inherent difficulty in assessing glycemic control in dogs with DM. Blood glucose concentrations are affected by many variables including stress, decreased appetite, variability in the amount of insulin administered and absorbed from the injection site, and concurrent infections or illnesses. To minimize the effects of stress and other variables on blood glucose concentration in dogs of the present study, we measured multiple parameters to evaluate glycemic control, namely SFCs, blood glucose concentrations through CGMS monitoring for up to 72 hours, and clinical scores that incorporated history and physical examination findings.

In addition, owner compliance with administration of the topical medications as prescribed could have impacted results of the present study. However, to minimize this potential problem, we trained owners on how to administer the medication properly, sent home a log for owners to complete, and called them weekly to discuss the medication schedule. Another limitation was that we did not measure plasma drug concentrations and thus did not determine the maximum absorption or area under the plasma drug concentration-time curve, both of which were beyond the scope of the present study. In addition, the lack of an untreated, negative control group limited the assessment to a drug comparison, as opposed to a treatment effect. However, we believed it would have been unethical to administer a placebo or no medication to dogs that had DM and cataracts because most are likely to have some degree of LIU.

Results of the present study supported our hypothesis that regulation of DM in dogs would not meaningfully differ between those treated with an ophthalmic preparation of prednisolone versus an ophthalmic preparation of diclofenac. Additional research is warranted on measuring the plasma concentrations of topically applied ophthalmic glucocorticoid medications.

Acknowledgments

The present study represents the continuation of a project reported in a thesisa and included data on 12 dogs from that thesis.

Supported by Morris Animal Foundation Grant D14CA-321, Kansas State University College of Veterinary Medicine Mark Derrick Canine Research Grant, and a Kansas State University Mentored Clinical, Applied, or Translational Research Grant. This publication has not been reviewed or endorsed by the Morris Animal Foundation, and the views expressed do not necessarily reflect the views of the Morris Animal Foundation or its officers, directors, affiliates, or agents.

The authors declare that there were no conflicts of interest.

Presented in abstract form at the 48th Annual American College of Veterinary Ophthalmologists Meeting, Baltimore, October 2017.

ABBREVIATIONS

CGMS

Continuous glucose monitoring system

DM

Diabetes mellitus

LIU

Lens-induced uveitis

LSM

Least squares mean

SFC

Serum fructosamine concentration

Footnotes

a.

Stuckey JA. Preliminary analysis of ophthalmic prednisolone acetate and diclofenac on diabetes mellitus regulation in 12 of 40 dogs. MS thesis, Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, Kan, 2014.

b.

Merck Animal Health, Madison, NJ.

c.

Bio-Glo fluorescein sodium ophthalmic strips, HUB Pharmaceuticals LLC, Rancho Cucamonga, Calif.

d.

TonoVet, Tiolat Ltd, Helsinki, Finland.

e.

SL-14, Kowa Co Ltd, Tokyo, Japan.

f.

Binocular indirect ophthalmoscope, Keeler LTD, Malvern, Pa.

g.

Guardian REAL-Time CGMS, Medtronic MiniMed Inc, Northridge, Calif.

h.

Pred Forte, Allergan, Irvine, Calif.

i.

Voltaren, Akorn, Lake Forest, Ill.

j.

PROC GLIMMIX, SAS, version 9.4, SAS Institute Inc, Cary, NC.

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Appendix

Variables assessed to determine individual clinical scores as an evaluation of DM control in 22 dogs with cataracts and well-controlled DM that received a topical ophthalmic preparation of either prednisolone acetate 1% (prednisolone group; n = 10) or diclofenac sodium 0.1% (diclofenac group; 12) administered in each eye 4 times daily for 28 days.

VariablesPoint values assigned
Patient history
 Need for insulin adjustment in previous 4 weeksYes (1 point) or no (0 points)
 Increased water consumptionYes (1 point) or no (0 points)
 Change in urine frequency, amount, or bothYes (1 point) or no (0 points)
 Increased appetite or food intakeYes (1 point) or no (0 points)
 Decreased activity levelYes (1 point) or no (0 points)
 Signs of hypoglycemia noticedYes (1 point) or no (0 points)
 Required treatment for hypoglycemiaYes (1 point) or no (0 points)
 Noncompliant with insulin, ocular medications, or bothYes (1 point) or no (0 points)
Physical examination
 ≥ 5% change in body weight from last examinationYes (1 point) or no (0 points)
 Body condition scoreUnacceptable (1/5 or 5/5; 1 point) or acceptable (2/5–4/5; 0 points)
 Hydration statusDehydrated (1 point) or clinically normal hydration (0 points)
 Cataract progressionYes (1 point) or no (0 points)
 Uveitis presentYes (1 point) or no (0 points)
Laboratory evaluations
 SFCUnacceptable (> 450 μmol/L; 1 point) or acceptable (≤ 450 μmol/L; 0 points)
 Insulin adjustment recommended after glucose curveYes (1 point) or no (0 points)

The total clinical scores recorded for each dog on days 0 and 32 were log transformed for generalized linear mixed-model analysis to assess potential differences between treatment groups throughout the period of observation.

Contributor Notes

Dr. Huey's present address is Memphis Veterinary Specialists, 555 Trinity Creek Cove, Cordova, TN 38018.

Dr. Fentiman's present address is Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078.

Address correspondence to Dr. Rankin (arankin@vet.k-state.edu).