Managing ocular allergy in the time of COVID‐19

To the Editor,

This spring, the majority of allergic patients are confined to their homes due to COVID‐19 pandemic restrictions. In the following weeks, these restrictions will be reduced and people will be allowed to take walks, go jogging, and return to work. Spring is the time for ocular allergy (OA) to emerge with signs and symptoms consequent to increasing pollen counts. Even when wearing a mask, the eyes may remain unprotected leading to an increase in ocular symptoms and patients seeking treatment for OA. However, access to routine consultation may remain problematic for many patients.

Diagnosis and management of allergic rhinoconjunctivitis is a common practice for allergists, pediatricians, rhinologists, ophthalmologists, and general practitioners. They are used to manage the most common forms of OA such as seasonal and perennial allergic conjunctivitis (SAC and PAC). The management of severe forms such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC), which can result in corneal complications and cause sight‐threatening sequelae, requires specialized expertise. ¹ VKC and AKC may require repeated courses of topical corticosteroids and/or long‐term use of topical immunomodulators. Immunosuppression, even localized to the ocular surface through the topical use of cyclosporine and tacrolimus, has the potential to increase susceptibility, persistence, and reactivation of any viral infection. Although the presence of SARS‐CoV‐2 in tears has rarely been detected in infected individuals, ² , ³ conjunctivitis may be a sign of COVID‐19, prior to or after the onset of respiratory symptoms. ⁴

Recommendations on the management of OA were recently published by the EAACI working group on OA (WG‐OA). ⁵ Considering the numerous problems due to the COVID‐19 pandemic, including the health system crisis and limited access to consultants, we were wondering whether established guidelines are still applicable. This letter reports the results of a survey conducted by members of the WG‐OA regarding the management of clinical forms of OA in the time of COVID‐19.

Twenty members of the WG‐OA and an additional 24 international experts in the field of ocular surface diseases were asked to complete a questionnaire using the Research Electronic Data Capture (REDCap) tool (Supporting information). Questions were closed‐ended and focused on the management of SAC, VKC, and AKC. Treatment options were stated for SAC and VKC/AKC patients experiencing active ocular symptoms in different situations: (a) not at risk of SARS‐CoV‐2 infection; (b) at risk of SARS‐CoV‐2 infection; (c) current SARS‐CoV‐2 infection; and (d) with previous SARS‐CoV‐2 infection (for definitions, see Supporting information). Two additional questions focused on the management of refractory AKC that may require systemic intervention or immunosuppression. Responses were selected from a Likert scale with 5 options (agree, partially agree, partially disagree, disagree, and no opinion). In addition, recommendations for OA treatment were evaluated to confirm agreement with published data ⁵ (Supporting information).

Results were obtained from 30 specialists, both from EU and other continents (18 ophthalmologists and 12 allergists). Their responses indicate that treatment options for SAC are still valid despite COVID‐19–related problems (Table 1). The use of low‐dose corticosteroids in case of no response was validated by the experts’ responses except in patients at risk of or with current SARS‐CoV‐2 infection. Topical antiallergic eye drops were validated by all consulted specialists. The use of oral antihistamine only remains an acceptable option for some of the respondents.

Table 1.

Treatment options for SAC

Topical antiallergic drops
SARS‐CoV‐2 infection	Agree	Partially agree	Partially disagree	Disagree	No opinion
Not at risk, n (%)	28 (93%)	1 (3%)	0	0	0
At risk, n (%)	29 (97%)	0	0	0	0
Current infection, n (%)	29 (97%)	0	0	0	0
Previous infection, n (%)	28 (93%)	1 (3%)	0	0	0
Low‐dose topical corticosteroids in case of no response
Not at risk, n (%)	14 (47%)	10 (33%)	1(3%)	3 (10%)	0
At risk, n (%)	10 (33%)	6 (20%)	1 (3%)	12 (40%)	0
Current infection, n (%)	9 (30%)	4 (13%)	3 (10%)	13 (43%)	0
Previous infection, n (%)	13 (43%)	10 (33%)	1 (3%)	6 (20%)	0
Only oral antihistamines
Not at risk, n (%)	10 (3%)	2 (7%)	4 (13%)	11 (37%)	0
At risk, n (%)	8 (27%)	8 (27%)	3 (10%)	9 (30%)	1 (3%)
Current infection, n (%)	6 (20%)	4 (13%)	6 (20%)	11 (37%)	0
Previous infection, n (%)	8 (27%)	1 (3%)	7 (23%)	11 (37%)	0

Regarding VKC/AKC, topical antiallergic drugs remain definitively the first‐choice treatment, with the addition of topical corticosteroids as the second‐choice treatment (Table 2). Regarding patients with current infection, there is disagreement on the choice of topical corticosteroid regimen; 57% of the respondents will use them as pulse therapy, while 14% a slow dose for long term (Table 2). There is good agreement on the use of topical immunomodulators in severe VKC/AKC patients not at risk of infection (90% agree), lower for patients at risk (66%), or with current infection (50%), while 77% agreed to use them in patients with previous infection.

Table 2.

Treatment options for VKC/AKC

Topical antiallergic drops
SARS‐CoV‐2 infection	Agree	Partially agree	Partially disagree	Disagree	No opinion
Not at risk, n (%)	26 (87%)	2 (7%)	0	0	0
At risk, n (%)	26 (87%)	0	1 (3%)	0	1 (3%)
Current infection, n (%)	26 (87%)	0	1 (3%)	0	1 (3%)
Previous infection, n (%)	25 (83%)	1 (3%)	1 (3%)	0	1 (3%)
Topical corticosteroids as needed as pulse therapy
Not at risk, n (%)	26 (87%)	2 (7%)	0	0	1 (3%)
At risk, n (%)	15 (50%)	9 (30%)	1 (3%)	2 (7%)	1(3%)
Current infection, n (%)	12 (40%)	7 (17%)	6 (20%)	4 (13%)	2 (7%)
Previous infection, n (%)	16 (53%)	10 (33%)	1 (3%)	1 (3%)	1 (3%)
Topical corticosteroids as needed at low dose but long term
Not at risk, n (%)	6 (20%)	2 (7%)	6 (20%)	10 (33%)	1 (3%)
At risk, n (%)	2 (7%)	5 (17%)	6 (20%)	13 (43%)	1 (3%)
Current infection, n (%)	2 (7%)	2 (7%)	7 (23%)	14 (47%)	2 (7%)
Previous infection, n (%)	4 (13%)	2 (7%)	9 (30%)	10 (33%)	1 (3%)
Topical calcineurin inhibitors
Not at risk, n (%)	20 (67%)	7 (23%)	1 (3%)	0	1 (3%)
At risk, n (%)	10 (33%)	10 (33%)	4 (13%)	2 (7%)	3 (10%)
Current infection, n (%)	8 (27%)	7(23%)	5 (17%)	7 (23%)	2 (7%)
Previous infection, n (%)	14 (47%)	9 (30%)	1 (3%)	2 (7%)	3 (10%)

The use of systemic immunosuppressant for severe AKC patients not responding to topical treatment was definitely not a consensual decision even before COVID‐19. We did not consider this question for patients with current SARS‐CoV‐2 infection because initiating immunosuppression in this case would be extremely rare and controversial. In severe, nonresponder AKC patients, the experts generally prefer local treatment in patients at risk (73%) and with previous infection (63%) (Table S1). The addition of systemic treatment/immunomodulation is not considered a good choice for patients at risk (most respondents disagreed or had no opinion), whereas in patients with previous infection, 50% of respondents recommended the addition of corticosteroids, 60% cyclosporine, 47% azathioprine, and 47% dupilumab. Furthermore, the present survey confirms that the recent EAACI WG‐OA recommendations for the management of OA ⁵ are well accepted and still valid in the time of COVID‐19 (Table S2, Supporting information).

As expected, the survey highlights some caution regarding the use of topical calcineurin inhibitors in severe VKC/AKC patients at risk and with current infection despite the negligible systemic absorption of topical cyclosporine. ⁶ Since eye rubbing is not recommended in any type of OA especially in time of COVID‐19, we suggest not to stop calcineurin inhibitors in severe VKC children at risk, while in patients with current disease the decision should be taken case by case. The risk of encountering a SARS‐CoV‐2–positive VKC patient is low, since the prevalence of VKC is estimated to be 4/10 000 under the age of 15 in Veneto Region (Italy) ⁷ and the prevalence of COVID‐19 cases under the age of 14 is about 1.5% in the same area, which has been one of the most affected areas in Europe. These numbers may be even lower in most EU and non‐EU countries but higher in areas, such as India and Africa, where VKC is more prevalent ⁸ , ⁹ and inappropriate use of steroids may lead to vision‐threatening complications. The use of systemic immunosuppression in severe AKC patients not responding to topical treatment remains a matter of debate that warrants case‐by‐case evaluation and multidisciplinary consensus.

The present survey was conducted within a panel of international ocular surface experts. The management of OA in the time of COVID‐19 should still follow the EAACI recommendations. ⁵ A particular caution is recommended for the use of corticosteroids and immunomodulators since a definitive consensus was not obtained, particularly for ongoing infected patients.

CONFLICT OF INTEREST

Dr Klimek reports grants and personal fees from Allergopharma, MEDA/Mylan, LETIPharma, and Sanofi; personal fees from HAL Allergy and Allergy Therapeut.; grants from ALK Abelló, Stallergenes, Quintiles, ASIT Biotech, Lofarma, AstraZeneca, GSK, and InmunoTek, outside the submitted work; and acts as a member of AEDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV GPA, and EAACI.

Supporting information

Table S1‐S2