A national survey of Canadian ophthalmologists to determine awareness of published guidelines for the management of uveitis

Uveitis, a group of ocular inflammatory conditions, accounts for 10 to 15 % of blindness in developed countries [1, 2]. As per standard nomenclature, chronic uveitis is defined as persistent uveitis characterized by prompt relapse (in less than 3 months) after discontinuation of therapy [3]. Persistent uveitis is defined as inflammation greater than 3 months in duration [3]. Recurrent uveitis is repeated episodes of uveitis separated by periods of inactivity without treatment, in which these periods of inactivity without treatment are at least 3 months in duration [3]. Sight-threatening disease arises from chronic, persistent, or recurrent inflammation. Left untreated or undertreated, chronic, persistent, or recurrent inflammation may lead to complications, such as cataract, glaucoma, macular edema, retinal or choroidal inflammation and atrophy, intraocular hemorrhage, or optic nerve atrophy. The therapeutic goal is to prevent vision loss from these complications by controlling or eliminating chronic, persistent, or recurrent inflammation. Systemic corticosteroid and locally administered corticosteroid injections treat ocular inflammation during acute episodes of uveitis, but the side effects of multiple pulse treatments or prolonged systemic corticosteroid administration limit their convenience as monotherapy for chronic and persistent uveitis, except in selected cases where dexamethasone or fluocinolone implants have been shown to be successful as monotherapy [4]. Persistent or chronic cases of uveitis, where corticosteroid therapy has failed to adequately treat disease, require long-term immunomodulatory therapy (IMT) to treat active inflammation and reduce the frequency of recurrences [5]. The uveitis management guidelines developed by an international panel of experts recommends the initiation of corticosteroid-sparing IMT if intraocular inflammation cannot be controlled with <10 mg/day of prednisone within 3 months [5]. However, in the recent survey of uveitis treatment patterns in the USA, Nguyen et al. showed that 75 % of the physician cohort surveyed was not aware of the aforementioned management guidelines [6]. The survey also indicated that the average corticosteroid dose was 44 mg/day and this dose was maintained for an average duration of 21 months, which is much higher than the recommended tapered doses of corticosteroids to <10 mg/day within 3 months [5]. The high doses of corticosteroid contributed to the significant adverse effects observed in the cohort of uveitis patients in the survey. Therefore, more widespread awareness of the uveitis treatment guidelines, leading to less reliance on corticosteroids, and appropriate timing of corticosteroid-sparing IMT would likely improve patient outcomes.

The purpose of this study is to assess, among Canadian ophthalmologists, the current awareness of published guidelines for the treatment of uveitis and to evaluate whether practice patterns are congruent with the published uveitis treatment guidelines. This study also assessed the frequency of applications to the government and private insurance providers for immunomodulatory drugs or biologics.

The response rate of the survey was 19.23 % (146/759), and 87.7 % (128/146) of respondents completed the survey in its entirety. Demographic and referral pattern data are detailed in Table 1. Among the respondents, 8.3 % (12/146; CI = 0.04–0.14) were uveitis specialists. A fellowship-trained uveitis specialist was present at 45.8 % (66/148; CI = 0.36–0.53) of the respondents’ center of residency training. Overall, 93.8 % (137/146; CI = 0.89–0.97) of the physicians’ practices consisted of less than 30 % of uveitis patients. The majority of respondents (73.3 %, 107/146; CI = 0.65–0.80) indicated they have referred patients to uveitis specialists.

Self-reported awareness of the uveitis management guidelines was 61.0 % (89/146; CI = 0.53–0.69), and 51.7 % (74/143; 3 no responses; CI = 0.43–0.60) of respondents indicated the utilization of these guidelines. The proportion of total correct responses to the clinical scenario questions was not statistically different (p = 0.547) between physicians who reported awareness of the aforementioned guidelines and those who did not. Awareness of guidelines did not differ significantly between respondents who were trained in uveitis (p = 0.127), respondents with sub-speciality training (p = 0.179), and presence of a fellowship-trained uveitis specialist at the respondent’s center of residency training (p = 0.232) (Table 2).

Adherence to the uveitis management guideline recommendations [1] was evaluated using clinical scenario questions. The association between adherence to guidelines and different training circumstances was assessed. A statistically significant difference in the proportion of total correct responses to clinical scenario questions was also found between those with fellowship training in sub-specialities and those with no fellowship training (p = 0.0145). However, the proportion of total correct responses to the clinical scenario questions was not statistically significant across the following groups of comparisons: whether the respondent had fellowship training in uveitis (p = 0.0509) and whether a uveitis specialist was present at the respondent’s center of residency (p = 0.698) (Table 3).

The year of residency completion was categorized into three groups: 1960 to 1980, 1981 to 2000, and 2001 to 2012. The proportion of total correct responses to clinical scenario questions in association with the year of residency completion is detailed in Table 3. When comparing the proportion of total correct responses in clinical scenario questions to the year of residency completion, there was a statistically significant difference between respondents who completed residency during 2000 to 2012 and those during 1960 to 1981 (p = 0.0208) and 1981 to 2000 (p = 0.0067). The selection of corticosteroid injections (intravitreal or periocular) in the clinical scenario questions, which was an incorrect response, was 7.1 % among graduates from 1960 to 1980, 12.4 % in graduates from 1981 to 2000, and 15.6 % in graduates from 2001 to 2012. Referral to a uveitis specialist was 90.0 % (27/30; CI = 0.73–0.98) among those who completed residency during 1960 to 1980, 76.6 % (59/77; CI = 0.63–0.83) for graduates in 1981 to 2000, and 53.8 % (21/39; CI = 0.37–0.70) in 2001 to 2012 (Fig. 1).

The frequency of IMT applications and success of obtaining IMT are shown in Table 4. When IMTs are required, 5.5 % of physicians (8/145; 1 no response; CI = 0.02–0.11) would prescribe the IMT themselves, while 54.5 % (79/145; CI = 0.46–0.63) would seek prescription of the IMT from a rheumatologist, dermatologist, or general internist, and 40.0 % (58/145; CI = 0.32–0.48) would refer to an ophthalmologist to coordinate the acquisition of IMT. Overall, 93.6 % (117/125; 21 no responses; CI = 0.88–0.97) of physicians make less than six IMT applications per year, and 89.0 % (105/118; 28 no responses) of respondents make less than six co-IMT applications with rheumatologists or other physicians. Less than 10 % of IMT applications was successfully obtained through private insurance and provincial drug coverage among 64.0 % of physicians (71/111; 35 no responses; CI = 0.54–0.73) and 56.5 % of physicians (61/108; 38 no responses; CI = 0.47–0.66), respectively. The frequency of IMT applications was 25.0 % (17/68; 78 no responses; CI = 0.15–0.37) for mycophenolate mofetil, 38.2 % (26/68; CI = 0.27–0.51) for cyclosporine, 32.4 % (22/68; CI = 0.22–0.45) for anti-tumor necrosis factor (TNF), and 36.8 % (25/68; CI = 0.25–0.49) for others.

Despite the well-recognized adverse effects of long-term corticosteroid usage, it has been the mainstay of uveitis management since its development [5, 7]. In addition to concerns about their adverse effects, high-dose systemic or locally injected corticosteroids, particularly serial periocular or intraocular corticosteroid injections, are not an optimal management strategy for chronic or frequently recurrent uveitis. At the time of writing, no Health Canada-approved immunomodulatory drugs are indicated for uveitis and all such drugs are used off-label. A sustained-release dexamethasone intravitreal implant (Ozurdex; Allergan, Inc., Irvine, CA, USA) and Retisert (Bausch&Lomb, Rochester, NY, USA) are currently the only Health Canada-approved treatments for uveitis. However, these implants are only indicated for posterior uveitis and not anterior or intermediate uveitis [5]. Although studies have demonstrated the effectiveness of Ozurdex for non-infectious posterior uveitis, the protracted disease course of some patients with chronic uveitis, measured in years and decades, is lengthy compared to the 6-month duration of a steroid implant [8]. When treatment with systemic corticosteroid and/or multiple local injections or implants have failed to reduce intraocular inflammation to an acceptable level, then corticosteroid-sparing IMT is warranted. An international expert panel has published guidelines recommending the appropriate initiation of corticosteroid-sparing IMT. [5]

To the best our knowledge, this is the first study examining the awareness of and adherence to uveitis management guidelines among Canadian ophthalmologists. This study described the awareness and utilization of the aforementioned guidelines, practice pattern variations across different years of residency completion, and the frequency of prescribing IMT and co-management of uveitis patients.

In conclusion, the awareness and utilization of the uveitis management guidelines among Canadian ophthalmologists can be improved. Furthermore, recent graduates were less likely to identify cases of uveitis where treatment with IMT is indicated. They were also more likely to manage uveitis with corticosteroid injections and less likely to refer patients to uveitis specialists. When use of IMT is necessary, the majority of ophthalmologists indicated that they would refer patients to uveitis specialists or other internists such as rheumatologists and dermatologists. Few applications for IMT were made by ophthalmologists, and majority of these applications were sent by non-ophthalmologists. Cumulatively, these results suggest the need for further education of Canadian ophthalmologists regarding uveitis treatment guidelines and the need to increase the number of uveitis specialists in Canada.