- Journal List
- HHS Author Manuscripts
- PMC7979495
As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsem*nt of, or agreement with, the contents by NLM or the National Institutes of Health.
Learn more: PMC Disclaimer | PMC Copyright Notice
Vet Ophthalmol. Author manuscript; available in PMC 2022 Mar 1.
Published in final edited form as:
Vet Ophthalmol. 2021 Mar; 24(2): 156–168.
Published online 2020 Dec 29. doi:10.1111/vop.12855
PMCID: PMC7979495
NIHMSID: NIHMS1659122
PMID: 33377263
DR Washington,1 Z Li,2 LC Fox,3,4 and FM Mowat1,5,*
Author information Copyright and License information PMC Disclaimer
The publisher's final edited version of this article is available at Vet Ophthalmol
Associated Data
- Supplementary Materials
Abstract
Background:
Canine sudden acquired retinal degeneration syndrome (SARDS) causes blindness for which there are no proven effective treatments. We aimed to clarify the time to vision loss, treatment response/side effects and prognosis for life in dogs with SARDS.
Methods:
An online questionnaire was administered to owners of dogs with a historical diagnosis of SARDS. Mortality data were compared with a published purebred reference population. Select parameters were analyzed statistically using general linear model with least square means, two-sample t-tests, and Chi-squared or Fisher’s exact tests.
Results:
Responses from owners that stated that their dog visited an ophthalmologist and had electroretinography performed (n = 434) were analyzed. The majority of owners (65.4 %) reported the time from vision disturbance to complete vision loss as < 2 weeks; 19.4% reported > 4 weeks. Onset of systemic clinical signs to complete vision loss was > 4 weeks in 44.5% of responses. A higher proportion of owners reported some vision recovery with combination treatment (14.4 %) compared with monotherapy (3.2 %, P =0.0004). Side effects of treatment were commonly reported. Dogs with SARDS did not have a shorter lifespan than the reference population but had higher incidence of kidney disease (P = 0.0001) and respiratory disease (P = 0.0004) at death.
Conclusions:
Dogs with SARDS have a rapid onset of vision loss. In the owner’s opinion, treatment is unlikely to restore vision and is associated with systemic side effects. The potential for systemic pathologies that arise after SARDS diagnosis warrants further study.
Keywords: Dog, SARDS, treatment, prognosis, onset time
Introduction
Sudden acquired retinal degeneration syndrome (SARDS) is associated with irreversible vision loss in dogs. Vision loss is described as sudden in onset; [1–3] one study reported that 100% of 26 dogs went blind within 4 weeks. [1] However, other studies have reported a small proportion of dogs that take greater than 4 weeks to lose vision. [3, 4] Whether there are differentiating features about these more protracted cases of vision loss remain to be determined. The systemic clinical signs and clinicopathologic abnormalities associated with SARDS have been well characterized in numerous studies. Typical associated signs and clinical findings include polyuria, polyphagia and weight gain, and laboratory findings consistent with liver damage and endocrinopathy, [3, 5–8] Differences between SARDS and canine pituitary-dependent hyperadrenocorticism have recently been described. [9] The timeframe between onset of systemic clinical signs and vision loss has not been described in detail, yet has been suggested to either precede vision loss or coincide with vision loss. [2]
There are few studies reporting the success rate of therapeutic intervention to recover vision in dogs with SARDS. The outer retina is already degenerate at the time of presentation to a veterinary ophthalmologist, [4, 9, 10] which raises concerns for the potential efficacy of treatments that aim to restore vision. A small prospective study of treatment with the immunosuppressive medication mycophenolate mofetil failed to improve vision in dogs with SARDS after complete vision loss. [11] Anecdotally, monotherapy with oral corticosteroids is ineffective in restoring vision. [5] Although combination therapy is proposed to be more effective than monotherapy in restoring vision, [12] 1 this has not been objectively evaluated. Because no controlled, prospective, peer-reviewed studies of these medications have been reported, an initial step of retrospective evaluation of treatment outcome might aid in planning and development of controlled clinical studies.
The course of systemic disease following vision loss in SARDS remains unreported, although one study suggested that greater than 50% of dogs with SARDS die or are euthanized within 1 year of diagnosis. [5] Further clarification of the types of systemic comorbidities with SARDS would help substantially in the clinical counseling provided to owners at the time of diagnosis.
We conducted a questionnaire targeted at owners whose dogs had historically suffered from SARDS. Despite the substantial limitations of retrospective nonclinical evaluation of outcomes from an owner questionnaire, we hypothesized that we might identify important trends in onset of clinical signs, as well as the effects and side effects of treatment when a large number of responses were collected. Our study had three main aims. First was to define the duration of time between the onset of either systemic clinical signs and vision loss, or visual disturbance and vision loss. Second was to determine the proportion of owners reporting vision improvement following treatment, and the proportion of those reporting side effects of treatment. Thirdly, we wished to establish the prognosis for life for dogs with SARDS. This work aimed to aid clinicians in the counseling of owners with respect to potential treatment benefits and risks, prognosis for life and to guide future clinical research studies.
Materials & Methods:
Questionnaire design and implementation:
A web-based online questionnaire (“Google Forms” Google Inc, Mountain View, CA, USA) was constructed to survey owner perceptions of canine sudden acquired retinal degeneration syndrome (SARDS). The full list of questions asked is included in Supplementary File 1. The survey consisted of 36 questions and took approximately 10 minutes to complete. Target participants were owners of dogs that had developed SARDS at any time in the past. The questionnaire was reviewed by the North Carolina State University Institutional Review Board and classified as “exempt” (protocol 11886).
Promotion of the questionnaire was through direct email requests to owners, sharing of the questionnaire with fellow comparative ophthalmologists, posting to the veterinary ophthalmology email listserv (approximately 700 members), laboratory social media accounts (Twitter, Facebook, Instagram), and posting on websites (Wikipedia, online blind dog forums, the American College of Veterinary Ophthalmologists Vision for Animals Foundation). Additionally, the questionnaire was emailed to owners of dogs diagnosed with SARDS at the North Carolina State University College of Veterinary Medicine between 2013–2018. These owners were identified by a keyword search of the medical record using the search terms: “sudden acquired retinal degeneration syndrome” “sudden acquired retinal degeneration” “SARDS” “SARD” “autoimmune retinopathy” “AIR”). Results from the questionnaire over a 2-year period (2017–2019) were analyzed. Due to differences in demographics, location data and treatment options available in different countries, replies were only analyzed from owners who resided within the United States of America.
Purebred reference population for mortality analysis:
A large published purebred reference population from the United Kingdom was used as a comparator for both age of death and diseases contributing to death in purebred dogs with SARDS. [13] Raw data from the published study was made available by the investigators, and was recoded and curated to ensure that datasets were comparable between the two studies with respect to causes of death, as the UK population included substantially more specific disease categories at death than were collected in our study. A similar dataset was not available from the United States, although a recently published article provided estimates of lifespan of different breeds extrapolated from categorical datasets collected from the Veterinary Medical Databases (VMDB) from 1984 to 2004. [14] We were not able to use these data for statisical analysis.
Mapping of SARDS case location:
The location of SARDS cases were mapped using provided zip code information with a commercial geographic information system (ArcMap, ArcGIS Desktop Release 10.1; Environmental Systems Research Institute, Redlands, CA). Successively, the 2010 zip code tabulation areas shapefile (the most current available) was retrieved from the US Census’ Tiger/Line database (United States Census, 2010).2 The X and Y coordinates for the geographic centroids for each zip code area were calculated in ArcMap using the calculate geometry tool. A join was then performed on the zip code attributes of the case database and zip code tabulation areas shapefile to assign each case to the geographic centroid of the zip code polygons.
The most up to date available demographic data (Number of Pets: Households 2019) was obtained using the Simply Analytics’ database. Simply Analytics data is disaggregated and extrapolated US Census Bureau’s American Community Survey data (SimplyAnalytics, 2019). Counties were used rather than zip codes for visual clarity when viewing the conterminous United States. Simply Analytics uses the WGS 1984 geographic coordinate system; whereas Tiger/Line uses North American 1983. Therefore, a geographic transformation was performed to ensure proper geographic alignment between the two datasets. The geographic X and Y coordinates of the demographic county polygon centroids were calculated again using ArcMap’s calculate geometry tool. A spatial join was subsequently used to link the zip code level case data to the demographic data. Then ArcMap’s summarize tool was used to aggregate the total cases to county-level, specifically the geographic centroid of each county.
Statistical analysis:
Not all owners provided responses to all questions, or responses were deemed unfeasible with curation (e.g. date of onset of SARDS was declared to be prior to animal’s declared date of birth); curation of data was performed to code data and remove clearly incorrect responses prior to analysis. Summary statistics were performed using statistical software (JMP Pro version 14.2.0, SAS, Cary, NC, USA). Shapiro-Wilk normality tests were performed on continuous data prior to statistical analysis. Mean and standard deviation is presented unless normality was not achieved when median and interquartile range is presented. The n-number of responses are presented for all data, and percentages of responses are also presented when n > 100 for the overall group size.
Further statistical analysis was performed using SAS software (version 9.4 for PC). Ages of onset in different breeds were summarized with means ± standard deviation (SD) and compared with general linear model with least square means. Age of death between SARDS and UK populations and between euthanized and non-euthanized dogs were compared with t-test. The remaining statistical comparisons were performed by Chi-square test, which included: month and season of onset, the outcome in relation to treatment initiation, visual outcomes, mild side effects and severe side effects between combination and monotherapy; the visual outcomes, mild side effects and severe side effects between steroid and non-steroid treatments; within subjects with steroid treatment, the outcomes, mild side effects and severe side effects between combination and sole therapy; causes of death between purebred SARDS and the UK purebred reference population. In the Chi-square test, if more than 25% of the cells had expected counts less than 5, Fisher’s exact tests were used.
Results
Population and method of SARDS diagnosis
Within the 2-year window that the questionnaire was administered, 662 responses were received from owners that lived within the United States of America at the time of their dog’s SARDS diagnosis. The majority of owners received a diagnosis of SARDS for their dog from a veterinary ophthalmologist (n = 563, 85.0%); of these dogs, the majority of owners stated they were confident that SARDS in their dog was confirmed by electroretinography (n = 434/563, 77.1% of dogs that visited an ophthalmologist, 65.6% of all responses). Further statistical analyses were only performed on data from dogs whose owners had stated they both visited an ophthalmologist and had an ERG performed (n = 434).
Signalment and onset
The mean age of onset was reported as 8.51 ± 2.60 years (n = 427). A total of 218 respondents reported their dog’s breed (Table 1). Mixed breed was the most common breed reported (n = 89, 40.1%). The most common purebred dog breed reported was the Dachshund (n = 36, 16.5%). There were no significant differences (Least squares mean, P value ranged from 0.46–0.91) in age of onset between different breeds (Table 1).
Table 1.
Age of onset stratified by breed disclosed by owner. Rows 2 onwards represent data only from those animals (per the respondent) that visited an ophthalmologist and had an ERG performed.
| Breed | N (%) of all dogs with disclosed breed | Mean ± SD age of onset (years) |
|---|---|---|
| All respondents | 656 | 8.65 ± 2.60 |
| Visited ophthalmologist and had ERG performed | 434 | 8.51 ± 2.60 |
| Purebred Dachshund | 36 (16.5 %) | 8.51 ± 2.60 |
| Purebred Miniature Schnauzer | 19 (8.7 %) | 9.28 ± 2.15 |
| Purebred Pug | 11 (5.0 %) | 8.75 ± 2.30 |
| Purebred other | 63 (28.9 %) | 8.83 ± 2.45 |
| Purebred all | 127 (58.3%) | 8.78 ± 2.38 |
| Mixed breed | 89 (40.1 %) | 8.43 ± 3.06 |
| Not disclosed | 216 | 8.38 ± 2.51 |
Open in a separate window
Vision loss was reported to occur throughout the year (Table 2); February (n = 48, 11.1%) was the most commonly reported month, and July was the least reported month (n = 22, 5.1%). There was no significant variance in month of onset (X2 (11, N = 434) = 13.6, P = 0.26). Winter (December-February) was the most commonly reported season of onset (n = 129, 29.7%), whereas summer (June-August) was the least reported season of onset (n = 89, 20.5%). There was no significant variance in season of onset (X2 (3, N = 434) = 7.4, P = 0.06).
Table 2.
Month of onset (total n = 434)
| Month | N (%) |
|---|---|
| January | 37 (8.5) |
| February | 48 (11.1) |
| March | 33 (7.6) |
| April | 38 (8.8) |
| May | 38 (8.8) |
| June | 30 (6.9) |
| July | 22 (5.1) |
| August | 37 (8.5) |
| September | 32 (7.3) |
| October | 40 (9.2) |
| November | 35 (8.1) |
| December | 44 (10.1) |
Open in a separate window
Only approximately half of owners (n = 238, 54.8%) reported the association of some life event with the onset of SARDS. Life events commonly reported included drug administration (n = 93, 17.1%) and vaccination (n = 75, 13.8%).
Home environment
The majority of owners fed their dogs commercially available dry dog food (n = 388, 74.5%) and/or wet dog food (n = 69, 13.2%), and gave their dogs tap water to drink (n = 267, 56.7%), although approximately a quarter of owners used filtered tap water (n = 115, 24.4%).
Owners predominantly reported that they and their dogs lived in a suburban home environment (n = 291, 67.1%). The remainder reported living in either a rural (n = 86, 19.8%) or urban (n = 57, 13.1%) environment. Using owner-provided zip code information, the location of dogs at the time of SARDS onset was mapped with available pet ownership data from the United States of America (Figure 1). Three zip codes did not correspond to those in the census shapefile database, 2 did not map as they did not correspond to information in the SimplyAnalytics database, therefore a total of 429 zip codes were mapped. There was a strong association between the location of cases and pet ownership, with 74.1% (318/429) of cases in counties with high pet ownership, 21.5% (92/429) of cases in counties with medium pet ownership and only 4.4% (19/429) cases in counties with historically low pet ownership.
Figure 1.
Mapping of reported cases of SARDS in the United States of America. Cases (429) were mapped using reported 5-digit zip code location at the time of vision loss. Locations of cases are superimposed on the historical pet ownership data from the 2010 US Census. The state of Hawaii is not shown as no cases were reported from that state. Pet density: low = 0–15,000, medium = 15,000–71,000, high = greater than 71,000
Associated clinical signs and findings
Although the majority of owners did not declare a notable difference between day and night vision in their dogs at SARDS onset (n = 292, 67.3%), more owners reported their dogs having greater difficulty seeing in dim light (n = 110, 25.3%) than those that reported their dogs having greater difficulty seeing in bright light (n = 32, 7.3%).
The majority of owners described that their dog had at least one systemic clinical sign in addition to blindness (n = 386`, 88.9%; Table 3). The most common reported clinical signs were polyphagia (65.9%), polydipsia (61.8%) and weight gain (60.4%). Approximately a third of owners (n = 137 31.6%) responded that they were confident that their dog had previously received a blood test result in which liver enzymes were determined to be elevated. A small minority of owners reported that their dogs had received a diagnosis of hyperadrenocorticism (Cushing’s disease; n = 37, 8.5%). Of the dogs that were reported as diagnosed with hyperadrenocorticism, 25 received some form of treatment, most commonly reported as trilostane (n = 20). Of the 25 treated dogs, just under half of owners (n = 11) reported an improvement in systemic clinical signs in response to treatment. Further questions regarding hyperadrenocorticism were not asked.
Table 3.
Frequency of systemic clinical signs (n = 434).
| Sign | N (%) |
|---|---|
| Polyphagia | 286 (65.9) |
| Polydipsia | 268 (61.8) |
| Weight gain | 262 (60.4) |
| Polyuria | 169 (38.9) |
| Sleep disturbance | 108 (24.9) |
| Worsening of coat condition | 88 (20.2) |
| Worsening of sense of smell | 77 (17.8) |
| Worsening of sense of hearing | 48 (11.1) |
| No systemic signs | 48 (11.1) |
Open in a separate window
Definition of the timeframe of vision loss
Owners were asked to define the time it took for their dog to have what they perceived as normal vision to them developing complete blindness. Including all dogs irrespective of treatment used (n = 434), the most common response was that vision loss took 1–3 days from normal to complete blindness (n = 94, 21.7%) and the majority of dogs completely lost vision within 2 weeks (n = 284, 65.4%). Including only dogs that did not receive any treatment (n = 234), the most common response was also that vision loss took 1–3 days from normal to complete blindness (n = 47, 20.1 %), and the majority of dogs completely lost vision within 1 week (n = 118, 50.4%). A small minority did not think that their dog ever went completely blind (5.5% of all dogs, 3.8% of untreated dogs). We further examined the responses that described a more protracted timeframe to vision loss. Approximately a third of owners responded that vision loss either remained incomplete long-term or took more than 2 weeks from onset to complete blindness (all dogs n = 150, 34.6%; untreated dogs n = 84, 35.9%). Approximately one in five reported that vision loss remained either incomplete or took more than 4 weeks from onset to complete blindness (all dogs n = 84, 19.4%, untreated dogs n = 45, 19.2%). A brief analysis of cases with a more protracted timeframe of complete vision loss (>4 weeks or never) was performed (Table 4). Owners of dogs with a longer timeframe of vision loss more commonly reported differences between day and night vision compared with those with a shorter timeframe of vision loss (P = 0.011). Owners of dogs with a longer timeframe of vision loss more commonly reported vision recovery with treatment than those with a shorter timeframe of vision loss (P = 0.005).
Table 4.
Select findings from cases in which owners reported a protracted period of vision loss (> 4 weeks or retained some vision) vs. lost vision within 4 weeks.
| Subcategory | Vision lost within 4 weeks | Vision lost in greater than 4 weeks or not lost completely | Statistical analysis (Chi-squared test) | |
|---|---|---|---|---|
| Difference between day and night vision | No difference | 247/350 (71%) | 45/84 (54%) | X2 (2, N = 434) = 9.05 P = 0.011 |
| Night worse than day | 79/350 (23%) | 31/84 (37%) | ||
| Day worse than night | 24/350 (7%) | 8/84 (10%) | ||
| Effect of treatment on vision | No effect | 113/146 (77%) | 19/37 (51%) | X2 (3, N = 183) = 13.09 P = 0.005 |
| Partial vision recovery | 7/146 (4.8%) | 7/37 (19%) | ||
| Full vision recovery | 1/146 (1%) | 1/37 (3%) |
Open in a separate window
Owners were also asked about the time it took from the onset of systemic clinical signs to complete vision loss. As noted above, a small minority of dogs did not develop any additional systemic clinical signs aside from vision loss (n = 48, 11.1%). In the dogs that did develop systemic clinical signs, approximately a quarter of dogs developed them at the same time as vision loss (n = 99, 25.9%). A further quarter of dogs developed signs within 1 month prior to vision loss (n = 90, 23.6%). A longer window of greater than 1 month prior to vision loss was described in the remainder (n = 193, 50.5% of dogs that developed systemic clinical signs, 44.5 % of all dogs).
As described above, owners were asked if they could recall if their dogs had suffered elevated liver enzymes on a routine blood screening test at any time prior to SARDS diagnosis. Of the owners that stated that their dogs had had elevated liver enzymes (n = 133, 30.6% of all responses), the most common response was that they were identified less than 6 months prior to SARDS onset (n = 59, 44.4% of dogs with elevated liver enzymes, 13.6% of all dogs). However, the remainder of the respondents (n = 74, 55.6% of dogs with elevated liver enzymes, 17.1% of all dogs) reported liver enzyme elevation of greater than 6 months prior to SARDS onset.
Treatment - response and side effects
Owners reported the use of any form of treatment for vision impairment in SARDS in 46.1% of responses (n = 200). Irrespective of the type or number of treatments used, owners confidently stated that any form of treatment resulted in some vision recovery (declared as either full or partial recovery of vision) in 8.7% of responses (16/183 responses; Table 5). Side effects were frequently reported. Mild (not life-threatening) side effects were reported to occur in 48.6 % of treated dogs, (89/183 responses, Table 5). Severe (potentially life threatening or altering) side effects were reported to occur in 6.7 % of treated dogs (12/180 responses, Table 5)
Table 5.
Treatments, effects and side effects. Ranked in order of frequency of administration of individual medications.
| Type of treatment | Route of administration | Number of treated dogs (%) | Monotherapy | Combination therapy | |||||
|---|---|---|---|---|---|---|---|---|---|
| Full or partial vision recovery | Mild side effects | Severe side effects | Full or partial vision recovery | Most frequent combination resulting in vision recovery (n) | Mild side effects | Severe side effects | |||
| Corticosteroids | oral | 109 (54.5%) | 1/41 | 29/42 # (69.0%) | 4/40 $ (10.0%) | 13/65 * (20.0%) | + parenteral steroid injection + thyroid supplementation (5) | 37/64 # (57.8%) | 6/64 $ (9.4%) |
| Thyroid supplementation | oral | 57 (28.5%) | 1/12 | 5/12 # (41.7%) | 0/12 | 7/40 * (17.5%) | + oral steroids + parenteral steroid injection (5) | 14/30 # (46.7%) | 3/30 $ (10%) |
| Other | NA | 49 (24.5%) | 0/16 | 3/15 | 0/15 | 4/30 * (13.3%) | + oral steroids + cyclosporine (2) | 23/40 # (57.5%) | 3/40 $ (7.5%) |
| Melatonin | oral | 28 (14.0%) | 0/8 | 1/8 | 0/8 | 0/15 | 7/16 # (43.8%) | 0/15 | |
| Corticosteroids | Topical ophthalmic | 24 (12.0%) | 1/5 * (20%) | 0/5 | 0/5 | 2/18 * (11.1%) | + oral steroids (2) | 6/18 # (33.3%) | 2/18 $ (11.1%) |
| Tetracyclines | oral | 24 (12.0%) | 0/1 | 0/1 | 1/1 $ (100%) | 1/22 | 9/22 # (40.9%) | 1/22 | |
| Cyclosporine | oral | 21 (10.5%) | 0/2 | 3/3 # (100%) | 0/2 | 3/18 * (16.7%) | + oral steroids + tetracycline (2) | 12/17 # (70.6%) | 2/17 $ (11.1%) |
| Corticosteroids | Parenteral injection (non-ocular) | 16 (8.0%) | NA | NA | NA | 5/16 * (31.3%) | + oral steroids + thyroid supplementation (5) | 10/16 # (62.5%) | 0/16 |
| Mycophenolate mofetil | oral | 11 (5.5%) | 0/8 | 3/8 # (37.5%) | 1/8 $ (12.5%) | 0/3 | 3/3 # (100%) | 0/3 | |
| Immunoglobulin | intravitreal | 9 (4.5%) | NA | NA | NA | 2/9 * (22.2%) | + oral steroids + other (2) | 5/9 # (55.6%) | 1/9 $ (11.1%) |
| Corticosteroids | Parenteral injection (ocular) | 5 (2.5%) | NA | NA | NA | 0/5 | 3/5 # (60.0%) | 0/5 | |
| Cyclophosphamide | oral | 3 (1.5%) | NA | NA | NA | 0/3 | 2/3 # (66.7%) | 0/3 | |
| Immunoglobulin | intravenous | 3 (1.5%) | NA | NA | NA | 1/3 * (33.3%) | + oral steroids + oral cyclosporine + oral tetracycline + oral niacinamide (1) | 1/3 # (33.3%) | 1/3 $ (33.3%) |
| Azathioprine | oral | 2 (1.0%) | NA | NA | NA | 0/2 | 1/2 # (50.0%) | 0/2 | |
| Niacinamide | oral | 1 (0.5%) | NA | NA | NA | 1/1 * (100%) | + intravenous immunoglobulin + oral steroids + oral cyclosporine + oral tetracycline (1) | 1/1 # (100%) | 1/1 $ (100%) |
| Any form of treatment | 200 (46.1% of all responses) | 3/93 (3.2%) | 44/94 # (46.8%) | 6/91 $ (6.6%) | 13/90 * (14.4%) | Oral steroids + parenteral steroid injection + thyroid supplementation (5) | 45/89 # (50.1%) | 6/89 $ (6.7%) | |
| No treatment | 234 (53.9% of all responses) | NA | NA | NA | NA | NA | NA | ||
Open in a separate window
Key:
*indicates >10% of treated animals had full or partial vision recovery reported in that treatment group
#indicates reported mild side effects affecting >25% of treated dogs
$indicates reported severe side effects affecting >5% of treated dogs.
Overall, owners reported a positive visual outcome significantly more frequently when combination therapy was used (14.4%, n = 13/90 responses; 9 medications were reported to recover vision in >5% of combination treated animals, X2 (1, N = 184) = 12.6, P = 0.0004, Table 5) compared with monotherapy (3.2% n = 3/93 responses; only monotherapy with topical corticosteroids was reported to recover vision in >5% of treated animals). The risk of mild (not life-threatening) and severe (potentially life threatening or altering) side effects was substantial with any form of therapy. The reporting of mild side effects with combination therapy (50.6%, n = 45/89, 15 medications were reported to result in mild side effects in > 25% of combination therapy treated animals, Table 5) was not significantly higher than with monotherapy (46.8%, n = 44/94, X2 (1, N = 184) = 0.05, P = 0.82, 4 medications were reported to result in mild side effects in > 25% of monotherapy treated animals). Steroid use in any form was associated with a significantly higher incidence of mild side effects (X2 (1, N = 184) = 19.38, P < 0.0001), but not severe side effects (X2 (1, N = 181) = 0.24, P =0.62). The reporting of severe side effects with combination therapy (6.7%, n = 6/89) was not significantly higher than with sole therapy (6.6%, n = 6/91, X2 (1, N = 181) = 0.17, P = 0.68), although only 3 medications were reported to result in severe side effects in > 5% of sole therapy treated animals compared with 8 medications in combination therapy treated animals.
Because of the multitude of combinations of therapy used, and the relatively low numbers of specific combinations administered, statistical analysis on the visual outcome and side effects of specific combination therapies was not performed. However, summary results are presented in Table 5. The most commonly used combination treatment that resulted in owners reporting some vision recovery was that containing a combination of oral steroids, injectable steroids and thyroid supplementation (n = 11 owners reported this combination, 1 reported partial vision recovery, 4 reported full vision recovery, 7/11 reported mild side effects, none reported severe side effects). Although less frequently used, combinations containing oral cyclosporine or immunoglobulin (intravitreal or intravenous) also reported vision recovery in > 10 % of treated animals, although many of these treatments had very low n-numbers (Table 5). Incidence of mild and/or severe side effects was high in all of the combination therapies in which greater than 10% of owners reported vision recovery (Table 5).
Treatment for the majority of dogs was initiated within 2 weeks of vision loss (62.7%, 116/185, Table 6). Statistical analysis did not identify a significant effect of the timing of treatment initiation on visual outcome (X2 (4, N = 181) = 9.17, P = 0.06), although an interesting and significant finding was that the highest proportion of vision recovery was reported by owners that reported they started treatment greater than 2 weeks after the onset of vision loss (Fisher’s exact test, P = 0.011; Table 6). It is important to note, however, that the highest proportion of vision recovery was also noted in dogs that had the longest time from initial visual disturbance to complete blindness, indicating that owners may have inadvertently attributed vision recovery to treatment, rather than incomplete vision loss in SARDS with a slower progression rate (Tables 4 and and6).6). Although it is possible that treatment was not administered for sufficient time to establish if it was efficacious, 55.6% (65/117) reported that they had treated their dog for greater than 1 month at the time of completing the questionnaire, and 29.1% (34/117) reported they had treated their dog for greater than 3 months (Table 6).
Table 6.
Timing of onset, and duration of treatment vs. reported outcome.
| Question | Option | Response indicating some vision recovery n/total responses |
|---|---|---|
| Initiation of treatment vs. onset of vision loss | <1 week | 5/68 |
| 1–2 weeks | 1/46 | |
| 2–4 weeks | 3/32 | |
| > 4 weeks | 7/29 # (24.1%) | |
| Don’t know/no answer | 0/8 | |
| Time from initial vision disturbance to complete blindness | <24 hours | 1/18 |
| 1–3 days | 3/41 | |
| 3–7 days | 1/29 | |
| 1–2 weeks | 2/33 | |
| 2–4 weeks | 1/25 | |
| 4–8 weeks | 3/17 # (17.6%) | |
| >8 weeks | 1/7 # (14.3%) | |
| Never went completely blind | 4/13 # (30.1%) | |
| Duration of treatment | < 1 month | 0/51 |
| 1–3 months | 1/31 | |
| 3–6 months | 1/7 # (14.3%) | |
| 6–12 months | 0/9 | |
| > 1 year | 4/17 # (23.5%) | |
| Don’t know/no answer | 9/68 # (13.2%) |
Open in a separate window
Key:
#indicates > 10 % respondents reported vision recovery
Prognosis for life
A total of 73 dogs had died by the time the owners filled out the survey. Dogs that received treatment had a mean age of death of 11.20 ± 2.33 years (n = 38) which was not significantly different to those that did not receive treatment with a mean age of death of 11.24 ± 2.20 years (n = 33, 2 sample t-test, Satterthwaite method, P = 0.72).
The mean age of death in dogs with SARDS was compared with a previously published population of purebred dogs from the United Kingdom (Table 7). [13] Responses that did not disclose a breed, or stated mixed breed were excluded from the comparison. A small number of dogs were euthanized because of circ*mstances related to SARDS (n = 3, 2.8 % of dogs that were reported to have died). Because euthanasia related to SARDS was not coded in the published reference population, these responses were excluded from the comparison with the published population. Purebred dogs with SARDS had a significantly longer lifespan compared with this reference population (Table 7, two sample Satterthwaite method t-test P < 0.0001). Although a comparable dataset from the United States was not available at the time of publication, data from a recent publication extrapolated from the Veterinary Medical Databases (VMDB) is presented in Table 7.[14] For the breeds listed (all purebred, Dachshund and Pug), age of death was similar in the United States population to that published in the United Kingdom population. The United States dataset represented estimates of longevity without a measure of variability; this therefore precluded statistical analysis.
Table 7.
Age of death distribution:
| Subgroup | SARDS population | UK Kennel club population[13] | US population[14] | |
|---|---|---|---|---|
| N number | All purebred | 37 | 5,653 | 19,360 |
| Dachshund | 14 | 112 | 1,297 | |
| Miniature Schnauzer | 4 | 76 | NA | |
| Pug | 5 | 24 | 201 | |
| Other purebred | 14 | 5441 | NA | |
| Mixed breed | 14 | NA | NA | |
| Breed not specified | 22 | 0 | 0 | |
| Mean ± SD age of death | All purebred | 11.53 ± 1.91 *** | 9.74 ± 4.01 | 10.43 $ |
| Dachshund | 12.33 ± 1.98 | 10.42 ± 4.57 | 10.24 | |
| Miniature Schnauzer | 10.93 ± 1.91 | 9.14 ± 4.52 | NA | |
| Pug | 10.58 ± 2.19 | 6.74 ± 4.55 | 9.47 | |
| Other purebred | 11.28 ± 1.62 | 9.75 ± 3.98 | NA | |
| Mixed breed | 11.09 ± 2.15 | NA | NA | |
| Breed not specified | 10.80 ± 2.79 | NA | NA |
Open in a separate window
***P<0.0001 compared with UK reference population (2 sample t-test Satterthwaite method).
$median age of death estimated from 40 different breeds.
NA not available.
Small n-numbers in the SARDS group in each purebred group precluded statistical analysis of individual breeds with respect to systemic diseases reported at the time of death (Table 8). There were substantial differences in the owner reported incidence of three diseases between purebred dogs with SARDS and the UK reference population. At the time of death, dogs with SARDS had a reported incidence of kidney disease (P = 0.0001), respiratory disease (P=0.0004) and pancreatic disorders (P = 0.002) that were >10% higher than the reference population. There was no difference in the owner reported incidence of immune-mediated conditions between the two groups at the time of death (P = 0.38).
Table 8.
Causes of death in SARDS (n = 36) and reference purebred dog populations (n = 5653).
| Disease category | SARDS all purebred: n | UK Kennel club population: n | P value (Two-sided Fisher’s exact test) |
|---|---|---|---|
| >10 % higher incidence in SARDS population | |||
| Kidney disorder | 9 (25%) | 308 (5%) | 0.0001 |
| Respiratory disorder | 5 (13.9%) | 93 (2%) | 0.0004 |
| Pancreatic disorder | 4 (11.1%) | 80 (1%) | 0.002 |
| <10% reported difference in incidence between groups (ordered from most to least significant) | |||
| Platelet disorder | 1 (2.8%) | 2 (<1%) | 0.02 |
| Heart disorder | 0 (0%) | 523 (9.3%) | 0.04 |
| None or old age | 4 | 1009 | 0.07 |
| Other | 5 | 366 | 0.09 |
| Neoplasia | 8 | 1920 | 0.12 |
| Liver disorder | 4 | 284 | 0.12 |
| Diabetes mellitus | 1 | 22 | 0.14 |
| Immune-mediated condition | 1 | 72 | 0.38 |
| Orthopedic disorder | 3 | 313 | 0.45 |
| Neurologic disorder | 6 | 685 | 0.45 |
| Gastrointestinal disorder | 2 | 260 | 0.68 |
| Hyperadrenocorticism | 0 | 52 | 1.0 |
| Don’t know | 2 | 298 | 1.0 |
| Trauma | 0 | 142 | 1.0 |
| Total number of animals | 36 # | 5653 | |
Open in a separate window
#excluded dogs euthanized primarily because of SARDS due to lack of comparator in reference population.
Discussion:
This study describes a large dataset of questionnaire-based epidemiologic information related to canine sudden acquired retinal degeneration syndrome (SARDS). Whilst we acknowledge that limitations of this study include the subjective nature of the responses and that information is derived from pet owners and not from clinicians, we provide consistently collected information showing substantial trends derived from a large number of responses. We have further defined the time window before complete vision loss both from the onset of vision impairment and from the onset of systemic clinical signs; the window is relatively narrow in most cases. Dog owners reported vision restoration in only a small proportion of treated dogs, and the incidence of reported treatment-related side effects is substantial. SARDS does not appear to shorten lifespan, but diseases related to mortality appear to differ from another published population. The findings we present will help to guide both clinical decision making and future research studies on SARDS.
Our survey population reflects findings in canine SARDS published in other studies. Mean age of onset was 8.51 years, similar to the previously published mean ages of between 8.4 and 9 years. [6, 8, 15] Mixed breed dogs were the most common breed affected in our study, similar to other studies. [5, 8, 15] One study did not find mixed breed dogs over-represented compared with their hospital population, [6] and it is possible that this breed’s overrepresentation reflects the high frequency of mixed breed dogs in the general population. In our study the most common purebred dog breeds were the Dachshund, Miniature Schnauzer and Pug, similar to other studies. [6, 8, 15–17] We did not identify a seasonal incidence of SARDS in responses taken throughout the United States. Similar to our findings, a study from Canada did not identify a strong seasonal different in incidence. [17] However, others have determined a higher incidence in winter in the Northeastern United States, [1, 2] and a higher incidence in summer in Northern California. [6]
Similar to other studies, owners of dogs with SARDS commonly reported concurrent clinical signs including polydipsia, polyphagia and weight gain and polyuria. [1–3, 5] A relatively high proportion of owners (10–25%) in our study also reported their dogs to have sleep disturbance, worsening of coat condition, worsening of olfaction or loss of hearing, indicating a broader range of systemic signs than previously reported. A small proportion of owners described definitive evidence of either liver enzyme elevation or a diagnosis of hyperadrenocorticism, although this may represent an underestimate as it relied on owner memory of a potentially distant past event, and it is likely that not all dogs underwent testing. A meta-analysis of previously published studies of dogs with SARDS reported that only 35% of reported cases had laboratory evidence supporting a diagnosis of hyperadrenocorticism, and none provided confirmatory test results, nor reported response to therapy. [9] Our findings suggest that at least a small proportion of dogs with SARDS have a subjective positive response to therapy for hyperadrenocorticism, indicating that the adrenocortical axis may be altered in a proportion of dogs with SARDS. The pathophysiology of endocrine disruption in canine SARDS remains unclear.
We identified no particular discriminating features of the dog’s history or home environment that strongly indicate specific risk factors for the development of SARDS. Dogs were predominantly fed commercial dry dog food and drank tap water. Further studies will be needed to establish if toxicant exposure in food and water sources are potential risk factors for canine SARDS, particularly as exposures could be cumulative over a protracted time period. The majority of dogs lived in suburban environments, and it appears this disease is not linked to a geographically based environmental pattern, but rather density of pets. It is feasible with additional data and analyses such as a multi-variate spatially based regression model or more wide-spread screening that geographic or environmental correlations with SARDS could be found. Environmental aspects such as air pollution, regional use of pesticides or other factors within or outside the home should be considered as potential risk factors for SARDS.
A main aim of this study was to more comprehensively define the timeframe of vision loss for canine SARDS. To achieve this aim, we asked owners about the time it took from onset of vision disturbance to complete vision loss. In addition, we asked about the time it took from onset of associated systemic clinical signs to complete vision loss, as the majority (88.9%) of owners reported at least one systemic clinical sign. Limitations to a questionnaire based assessment is the likely heterogeneity in perception of owners and subjective nature of the assessment. The majority of dogs (65.4%) lost vision within 2 weeks from the onset of vision disturbance, with the most common response being complete vision loss within 1–3 days. Only 19.4% reported that their dog took more than 4 weeks to lose vision, similar to the 12% reported in a previous study. [3] Owners of dogs with slower onset of vision loss were significantly more likely to report changes in bright or dim light vision as part of the disease onset, compared with the owners of dogs with a quicker onset of vision loss. It is possible that some of these dogs represent diseases other than SARDS, or that this is a unique type of SARDS that preferentially affects photoreceptor subtypes. An interesting additional finding was that dogs that experienced a more protracted timecourse of vision loss had a significantly greater reported treatment response than those that lost vision more quickly. Whether this represents either early intervention that delayed or prevented vision loss, a more protracted clinical course of SARDS, or a different disease pathophysiology in certain animals remains to be established. Our question relating to the timing of other systemic clinical signs (apart from vision disturbance) did not reveal a substantially longer timeframe. Only just over 50% of dogs developed systemic clinical signs greater than 1 month prior to complete vision loss. Because of the nonspecific nature of these clinical signs (overlapping with conditions such as endocrinopathy and kidney disorders), this represents a greater diagnostic challenge for SARDS than the onset of vision disturbance. However, there are clear routine laboratory test differences between SARDS and canine hyperadrenocorticism, [9] which might aid in earlier referral to an ophthalmologist. Identification of an independent early SARDS biomarker with high specificity and sensitivity would be optimal and may also shed light on the as-yet poorly understood pathophysiology of this disease.
A second main aim of this study was to objectively evaluate the range of treatments for SARDS used in clinical practice, and the owner perceptions of efficacy of these treatments to restore vision in their dogs. Whilst limitations of these findings include the lack of objective clinical verification of treatment response and the heterogeneity of treatment approaches, this information may prove valuable for ophthalmologists when counseling clients on the balance between the potential positive benefit of vision restoration and the negative side effects of the treatments. Just under half of respondents chose to treat their dogs, which is higher than the 22% of owners in a previously published study. [5] We did not explore the reasons for owners choosing not to treat; it may represent a lack of opportunity, finances, or motivation, or a combination thereof. Of all treated dogs, vision improvement was reported in 8.7% of responses, and combination therapy resulted in a greater proportion of owners reporting subjective vision improvement than monotherapy. This supports previous studies: monotherapy with mycophenolate mofetil did not restore vision in an open label prospective study, [11] and anecdotally, monotherapy with steroids also did not restore vision as perceived by owners. [5] It must be emphasized that side effects, both mild and severe were common with any form of therapy and were often equal or greater in frequency than the frequency of vision restoration. Multiple recent studies have demonstrated the presence of substantial outer retinal degeneration very soon after the onset of complete vision loss in SARDS. [4, 9, 10] This is consistent with the hypothesis that vision loss and photoreceptor degeneration are temporally correlated and is likely to limit the efficacy of treatment in restoring vision. Careful counseling of owners regarding the balance between benefit and risk is an important component of informed consent when offering treatment for SARDS, considering the relatively low success rates reported by owners in our study.
A third aim of the study was to determine factors surrounding death in dogs with SARDS. Overall, treatment did not substantially shorten lifespan compared with dogs that did not receive treatment. Whilst limitations of longevity comparisons include the lack of inclusion of mixed breed dogs, and the lack of a comparable reference population from the United States, meaningful conclusions can still be made. Overall, the age of death in purebred dogs with SARDS was significantly older compared with the large reference population from the United Kingdom, [13] or extrapolated data from the United States. [14] However, there were substantial differences in the diseases that owners reported at the time of death in dogs with SARDS compared with the UK reference population. Namely, kidney disease, respiratory disease and pancreatic disorders had a substantially higher incidence in dogs with SARDS. There was also smaller magnitude but statistically significantly higher incidences of platelet disorders and heart disease in dogs with SARDS. Interestingly, there were no higher reported levels of immune-mediated disease in dogs with SARDS at the time of death compared with the comparator population, in contrast to a previous study which described that 59% (13/22) of SARDS owners reported a historical presence of immune-mediated disease. [4] Our findings may aid in the counseling of owners in future monitoring of their dogs with SARDS, to facilitate timely medical therapy to address systemic conditions such as kidney disease. This finding also provides rationale for the study of pathology of these organs in dogs with SARDS to shed further light on pathophysiology. Immune system activation is implicated in the pathophysiology of canine SARDS. [4, 18] In particular, dogs with SARDS have elevated concentrations of circulating IgM [18] which may contribute to immune complex deposition or thrombosis with subsequent damage to end organs such as the kidney.
Supplementary Material
supplementary file 3
Supplementary File 3. Key for coding of questionnaire raw data
Click here to view.(12K, xlsx)
supplementary file 2
Supplementary File 2. Coded raw data from questionnaire used in data analysis in this manuscript (n = 434, visited ophthalmologist and had ERG performed)
Click here to view.(70K, xlsx)
Supplementary file 1
Supplementary File 1. Complete list of questions and available answers for questionnaire reported in this manuscript.
Click here to view.(229K, pdf)
Acknowledgements
The project was funded in part by NIH K08 EY028628 to FM. Data analysis was supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR002373. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Other funding sources include the ACVO Vision for Animals Foundation and the North Carolina Veterinary Medical Foundation Retinal Research Fund. We gratefully acknowledge data supplied by the UK Kennel Club.
Footnotes
Conflict of interest disclosure:
The authors have no relevant conflicts of interest to declare.
1Unpublished observations, Dr. Al Plechner, http://drplechner.com/sards-corner/, accessed 5/9/2020
2TIGER/Line Shapefiles. Retrieved April 11, 2020, from https://www.census.gov/geographies/mapping-files/time-series/geo/tiger-line-file.html
References
1. Acland GM, Irby NL, Aguirre GD, Gross S, Nitroy SF, Notarfrancesco K. Sudden acquired retinal degeneration in the dog: clinical and morphologic characterization of the “silent retina” syndrome. Transactions of the American College of Veterinary Ophthalmologists. 1984; 15: 18. [Google Scholar]
2. Acland GM, Aguirre GD. Sudden acquired retinal degeneration: clinical signs and diagnosis. Transactions of the American College of Veterinary Ophthalmologists. 1986; 17: 6. [Google Scholar]
3. Van der Woerdt AN, M.P., Davidson MG. Sudden acquired retinal degeneration in the dog: clinical and laboratory findings in 36 cases. Prog Vet Comp Ophthalmol1991; 1: 8. [Google Scholar]
4. Grozdanic SD, Lazic T, Kecova H, Mohan K, Kuehn MH. Optical coherence tomography and molecular analysis of sudden acquired retinal degeneration syndrome (SARDS) eyes suggests the immune-mediated nature of retinal damage. Vet Ophthalmol2019; 22: 305–327. [PMC free article] [PubMed] [Google Scholar]
5. Stuckey JA, Pearce JW, Giuliano EA, Cohn LA, Bentley E, Rankin AJ, Gilmour MA, Lim CC, Allbaugh RA, Moore CP, Madsen RW. Long-term outcome of sudden acquired retinal degeneration syndrome in dogs. J Am Vet Med Assoc2013; 243: 1425–1431. [PubMed] [Google Scholar]
6. Auten CR, Thomasy SM, Kass PH, Good KL, Hollingsworth SR, Maggs DJ. Cofactors associated with Sudden Acquired Retinal Degeneration Syndrome: 151 dogs within a reference population. Vet Ophthalmol2018; 21: 264–272. [PubMed] [Google Scholar]
7. Carter RT, Oliver JW, Stepien RL, Bentley E. Elevations in sex hormones in dogs with sudden acquired retinal degeneration syndrome (SARDS). J Am Anim Hosp Assoc2009; 45: 207–214. [PubMed] [Google Scholar]
8. Montgomery KW, van der Woerdt A, Cottrill NB. Acute blindness in dogs: sudden acquired retinal degeneration syndrome versus neurological disease (140 cases, 2000–2006). Vet Ophthalmol2008; 11: 314–320. [PubMed] [Google Scholar]
9. Oh A, Foster ML, Williams JG, Zheng C, Ru H, Lunn KF, Mowat FM. Diagnostic utility of clinical and laboratory test parameters for differentiating between sudden acquired retinal degeneration syndrome and pituitary-dependent hyperadrenocorticism in dogs. Vet Ophthalmol2019. [PubMed]
10. Osinchuk SC, Leis ML, Salpeter EM, Sandmeyer LS, Grahn BH. Evaluation of retinal morphology of canine sudden acquired retinal degeneration syndrome using optical coherence tomography and fluorescein angiography. Vet Ophthalmol2019; 22: 398–406. [PubMed] [Google Scholar]
11. Young WM, Oh A, Williams JG, Foster ML, Miller WW, Lunn KF, Mowat FM. Clinical therapeutic efficacy of mycophenolate mofetil in the treatment of SARDS in dogs-a prospective open-label pilot study. Vet Ophthalmol2018; 21: 565–576. [PubMed] [Google Scholar]
12. Grozdanic SD, Kecova H, Chatzistefanou M, Lazik T. Therapeutic outcomes in sards dogs with presence of normal day vision and completely absent retinal electrical activity (abstract). 47th Annual Meeting of the American College of Veterinary Ophthalmologists. 2016; 19: E21–E43. [Google Scholar]
13. Lewis TW, Wiles BM, Llewellyn-Zaidi AM, Evans KM, O’Neill DG. Longevity and mortality in Kennel Club registered dog breeds in the UK in 2014. Canine Genet Epidemiol2018; 5: 10. [PMC free article] [PubMed] [Google Scholar]
14. Yordy J, Kraus C, Hayward JJ, White ME, Shannon LM, Creevy KE, Promislow DEL, Boyko AR. Body size, inbreeding, and lifespan in domestic dogs. Conserv Genet2020; 21: 137–148. [PMC free article] [PubMed] [Google Scholar]
15. Heller AR, van der Woerdt A, Gaarder JE, Sapienza JS, Hernandez-Merino E, Abrams K, Church ML, La Croix N. Sudden acquired retinal degeneration in dogs: breed distribution of 495 canines. Vet Ophthalmol2017; 20: 103–106. [PubMed] [Google Scholar]
16. Stromberg SJ, Thomasy SM, Marangakis AD, Kim S, Cooper AE, Brown EA, Maggs DJ, Bannasch DL. Evaluation of the major histocompatibility complex (MHC) class II as a candidate for sudden acquired retinal degeneration syndrome (SARDS) in Dachshunds. Vet Ophthalmol2019. [PMC free article] [PubMed]
17. Leis ML, Lucyshyn D, Bauer BS, Grahn BH, Sandmeyer LS. Sudden acquired retinal degeneration syndrome in western Canada: 93 cases. Can Vet J2017; 58: 1195–1199. [PMC free article] [PubMed] [Google Scholar]
18. Mowat FM, Avelino J, Bowyer A, Parslow V, Westermeyer HD, Foster ML, Fogle J, Bizikova P. Detection of circulating anti-retinal antibodies in dogs with sudden acquired retinal degeneration syndrome using indirect immunofluorescence: A case-control study. Exp Eye Res2020: 107989. [PubMed] [Google Scholar]
