1. Introduction
Prolapsed nictitans gland (“cherry eye”, PNG) of dogs is a condition commonly encountered by veterinarians, particularly in predisposed breeds [
1,
2]. Multiple surgical procedures for correction have been described in the veterinary literature which require varying surgical proficiency and equipment [
3] (pp. 963–964). Gland excision has been discouraged due to recognition of the gland’s contribution to tear production and a study showing higher risk of keratoconjunctivitis sicca (KCS) in dogs after excision [
3] (p. 963) [
4] (p. 80) [
5] (p. 163) [
6] (p. 206) [
7] . Apart from this fiat, we are unaware of any directive guidance for management of cherry eye, with surgical technique currently considered a matter of personal preference [
3] (p. 964). Similarly, feline herpesvirus (FHV-1) may result in morbid and relapsing corneal and conjunctival disease in cats. In contrast to cherry eye, definitive diagnosis of FHV-1 keratitis is challenging even with molecular testing [
8,
9]. No veterinary drugs are labelled for herpetic keratitis and there is little clinical research to guide treatment decisions in naturally occurring disease [
8,
9].
In human medicine, greater treatment variation may occur for conditions which lack high level evidence or guidelines [
10]. Vignette-based questionnaires have been used to assess treatment patterns and variation in human clinical practice, as well to identify areas of clinical uncertainty [
11,
12,
13]. Use of open, rather than closed, questions in vignettes may provide better insight into actual current practice [
14]. We are unaware of any published literature documenting treatment patterns of these two ocular disorders in first opinion or ophthalmology practice. Ophthalmology practice patients may differ from primary care in a number of ways: cases may vary in severity, as well as available owner resources and practice capabilities. Heterogeneous management strategies may highlight resource and evidence gaps encountered by veterinarians in the treatment of these conditions and identify areas of priority for research in veterinary ophthalmology. The aim of this study was to survey veterinarians about their management of PNG in dogs and herpetic keratitis in cats. Additionally, we sought to explore variation in treatment amongst all veterinarians and between veterinarians in general practice (GPs) and those with additional ophthalmology training (PGs), with reference to published evidence regarding the treatment of these conditions.
4. Discussion
There appeared to be variation in treatment recommendations elicited by clinical vignettes of PNG and FHV-1 keratitis, which could potentially impact on the consistency of care given to animals affected by these conditions. Prior work has demonstrated treatment variation in cardiac, endocrine, and ocular diseases of companion animals [
15,
18,
19,
20]. This study provides additional evidence for such variation: although suggestions for initial treatment of PNG were generally consistent amongst all veterinarians, approaches to surgical failure varied more between GPs and PGs. Moreover, a wider range of treatments were suggested for FHV-1 keratitis, with larger discordance between GPs and PGs in the use of systemic agents.
Most respondents suggested surgical replacement of PNG, although more GPs trialed medical therapy prior to surgical intervention. Most chose a pocket procedure for initial repair (when the technique was specified). Although a variety of techniques for gland replacement have been published [
7,
21,
22,
23,
24,
25,
26,
27,
28], there is limited data for comparative efficacy on surgical and lacrimal outcomes, particularly for breeds thought to be at higher risk for recurrence or for development of KCS. Morgan’s pocket technique is considered technically less challenging than some other procedures and is frequently covered in ophthalmology surgical texts [
3,
4,
5,
6,
29], factors which may have driven popularity amongst respondents. Our finding that periosteal anchoring was suggested more frequently by PGs for revision surgery suggests that it may be favored in patients more prone to recurrence, a view reinforced by some authors [
28,
30] and a recent study showing decreased recurrence in English Bulldogs when pocketing was augmented with a periosteal tack [
22]. It is noteworthy that some of the GPs in our survey suggested referral specifically for periosteal anchoring, suggesting less comfort with the surgical technique in that group.
A significantly greater number of GPs considered gland excision in the case of first surgery failure. Gland excision, though commonly recommended in the past [
31], is currently discouraged due to published evidence of concomitant reduction of tear production [
32,
33,
34,
35]. Although a retrospective study associated excision with subsequent development of KCS [
7], a number of respondents who suggested excision as a treatment option stated that they had never encountered this complication. KCS risk varies by sex, breed, and age [
36,
37,
38]. It is likely that excision-related KCS may similarly vary and that willingness to excise may reflect experience with patient mix that is not fully captured by the published literature. Alternatively, since prolonged prolapse may also be associated with higher KCS risk [
7], respondents may have suggested excision to serve owner cosmetic and financial preferences, rather than lacrimal function. Finally, since onset of KCS often occurs years after excision (mean 3.06 years, median 4.5 years [
7]), it is possible that clinicians who did not report this complication may have been biased by shorter follow-up times.
Currently and at the time of this survey, there are no approved veterinary pharmaceutical products for the treatment of FHV-1 keratitis. Suggested therapeutics have generally been derived from in vitro efficacy studies, experimental infection, and case series reports [
8,
39]. Topical antibiotics (recommended by the majority of all respondents) are used in both human and feline keratitis primarily for the prevention and treatment of secondary infection [
8,
9,
40,
41]. Although the difference did not reach statistical significance, more PG respondents recommended use of a lubricant. We speculate that lubricants may have been suggested due to tear film abnormalities documented in cats experimentally infected with FHV-1 [
42], as well as to improve ocular comfort [
30].
Although a similar proportion of PGs and GPs recommended a topical antiviral, product choice was disparate between groups, with a larger proportion of PGs suggesting trifluorothymidine. This may be due, in part, to limited availability of some topical preparations in the UK; trifluorothymidine must be obtained through the single national ophthalmic compounding pharmacy in the UK. However, aside from a controlled trial of cidofovir [
43], topical antiviral efficacy has generally been deduced from in vitro and uncontrolled observational data [
39]; perhaps as a consequence, disparate product recommendations are common in veterinary references [
5] (pp. 396–399) [
30] (p. 250) [
44] (p. 470).
General practitioners and PGs diverged more dramatically in their systemic FHV-1 therapy recommendations, notably in the greater popularity of famciclovir and lysine amongst PGs. At the time of this survey, preliminary experimental safety and efficacy data for famciclovir in feline FHV-1 had been published, along with a small case series [
45,
46,
47]. However, famciclovir therapy had not yet been included in contemporary texts or was discouraged due to safety concerns [
48] (p. 145) [
30] (p. 72) [
44] (p. 470). Lysine recommendations also varied between authors at the time of this survey. The European Cat Advisory Board included lysine as a recommended antiviral agent in their 2009 guidelines [
9] whilst a contemporary evidence-based management guide suggested that lysine was futile at best and could potentially worsen disease and viral shedding [
8]. Two recent systematic reviews summarizing evidence available at the time of this survey have also suggested no evidence for lysine in prevention or treatment of FHV-1 or prevention of human herpes simplex labialis [
49,
50]. However, lysine is still considered potentially beneficial by some veterinary ophthalmologists and virologists [
39,
51]. Our survey was not designed to elicit reasons for variation but we speculate that the lower number of lysine suggestions from GPs might reflect differences in information sources, evidence appraisal, or product availability between the two groups.
Although stress avoidance and recognition of FHV-1 chronicity emerged as consensus themes amongst respondents, vaccine recommendations varied by practitioner group. Current vaccine guidelines vary in suggested FHV-1 vaccine intervals due to non-sterilizing immunity and uncertainty regarding duration of immunity [
9,
52]; some suggest that FHV-1 may recrudesce in latent carriers following modified live FHV-1 vaccination [
51,
53]. Thus, practitioner recommendations may vary depending on information source. Finally, we were struck by numerous and varied additional recommendations for management of FHV-1 keratitis. It has been suggested that treatment proliferation occurs for chronic disease in which little is known and empirical therapy forms the basis for practice [
54] (p. 63).
Treatment variation in human medicine is greater in areas with larger evidence gaps and for conditions which lack clinical guidelines [
10]. Additionally, physician social networks have been shown to drive regional variation in prostate cancer and coronary artery disease care in the United States [
55,
56]. In veterinary medicine, few high quality clinical trials are available, constraining information sources to lower levels of evidence [
57]. In this environment, information sources, social networks, and client preferences may drive care more substantially and further work in identifying the sources of veterinary treatment variation is needed. While guidelines may help reduce heterogeneity in clinical decision making, they are ideally formulated using best available evidence alongside inclusion of all stakeholders into the guideline process. Our results, combined with the accompanying survey of current evidence, suggest that there is need for both guidelines for companion animal ocular disease and additional research to establish optimal treatment for these conditions. In the low resource setting of veterinary medicine, electronic medical records could be leveraged to collect multicentre cohort data, create patient registries, and serve as the basis of pragmatic clinical trials.