Ocular Allergies Treatable With Subcutaneous and Sublingual Therapy, Report Says

Close up of a red eye.
Report reviews the utility of allergy-specific immunotherapy in allergic rhinoconjunctivitis.

Both subcutaneous and sublingual allergy-specific immunotherapy are associated with improvements in allergic conjunctival symptoms, but considerations for cost, time commitment, and adverse events must be made, according to a review article published in Current Opinions in Allergy and Clinical Immunology.1 

Roughly 40% of the population in the United States is affected by allergic eye disease, costing between $2 and $4 billion annually.1 But because conjunctival symptoms are not spontaneously reported on questionnaires or in interviews focused on rhinitis or asthma, the true prevalence of allergic conjunctivitis is unknown.

Current management strategies for ocular allergies include environmental control measures in conjunction with pharmacotherapy, immunotherapy, herbal treatments, ocular lubricants, lipid conjugates, and/or physical barrier devices.1 However, only allergen-specific immunotherapy has been demonstrated to modify the process of the disease. 

Allergic eye disease is categorized by anterior ocular surface inflammation mediated by environmental aeroallergens. These allergens stimulate particular immunoglobulin E (IgE)-mediated mast cells to degranulate, releasing inflammatory markers. Allergen-specific immunotherapy induces a 4-stage cascade of immune responses at both the cellular and molecular level to modulate the processes of this disease. 

Subcutaneous immunotherapy is the standard for allergen-specific immunotherapy.1 Although the literature has primarily focused on the relief of nasal, not ocular, symptoms, recent years have seen the emergence of evidence supporting subcutaneous immunotherapy for symptomatic conjunctival symptom relief. 

Sublingual immunotherapy is a less common treatment option for conjunctival symptom relief. The first major systematic review on sublingual immunotherapy, published in 2011, found that within 42 trials, sublingual immunotherapy was “moderately effective” in reducing both total and individual ocular symptom scores in people with allergic conjunctivitis.2 More recent publications continue to support the clinical efficacy and utility of sublingual immunotherapy in the management of allergic conjunctivitis, with a particular multinational meta-analysis of pediatric studies finding that the treatment modality effectively reduced ocular symptom scores vs placebo and a prospective, case control study identifying a decrease in allergic conjunctivitis symptoms scores due to dust mites.1,3

A prospective, comparative case-series study comparing sublingual and subcutaneous immunotherapy found a significant reduction in total IgE and wheal diameter of skin prick testing following either treatment compared with baseline; no significant between-group differences in terms of total ocular symptom scores were noted favoring either subcutaneous or sublingual immunotherapy.4 In terms of long-term efficacy after treatment discontinuation, data indicated significant control within the first 5 years following treatment discontinuation.5 

Both treatment modalities have been associated with adverse events. A previously reported adverse event rate of 61% with sublingual immunotherapy was found to encompass predominantly localized, mild to moderate symptoms such as oral pruritis and throat irritation.6 Adverse events frequently occur within the first month (56% of patients) or first week (93% of patients) and more than half of these reactions last less than 2 days and most resolve spontaneously.7 

In comparison, subcutaneous immunotherapy has been associated with delayed systemic reactions within 30 minutes of administration. This treatment modality requires in-office monitoring for adverse events.8

For polyallergic patients, subcutaneous immunotherapy preparations in the United States contain 8 allergens on average.8 Despite the demonstrated efficacy of this type of subcutaneous immunotherapy, there is no consensus on the safety or efficacy of administering multiple sublingual immunotherapy products in combination, limiting its applicability in polyallergic populations.1

Allergen-specific immunotherapy requires at least 3 years of adherence for success.1 Numerous studies have compared the rates of discontinuation of nonadherence in both sublingual and subcutaneous immunotherapy. Patients in a 2012 study cited inconvenience as a primary reason for discontinuing sublingual immunotherapy, while patients receiving subcutaneous immunotherapy indicated that they discontinued treatment due to efficacy concerns.9 

“For correctly selected patients, [subcutaneous or sublingual immunotherapy] is recommended for allergic rhinoconjunctivitis as it is safe and well-tolerated when appropriately administered,” according to investigators.1 “Both will offer improvement in conjunctival symptom and medication utilization scores…[and] although limited economic analyses currently favor [subcutaneous immunotherapy,], successful interventions to improve [sublingual immunotherapy] adherence need to be developed.” 

“The decision for either [subcutaneous or sublingual immunotherapy] remains a patient-directed decision, with adherence being the greatest hurdle for either method of administration,” the researchers explain.1 


  1. Norris MR, Khaimov M, Bielory L. Use of allergen immunotherapy for treatment of allergic conjunctivitis. Curr Opin Allergy Clin Immunol. 2020;20(6):609-615. doi:10.1097/ACI.0000000000000692.
  2. Calderon MA, Penagos M, Sheikh A, Canonica GW, Durham SR. Sublingual immunotherapy for allergic conjunctivitis: Cochrane systematic review and meta-analysis. Clin Exp Allergy. 2011;41(9):1263-1272. doi:10.1111/j.1365-2222.2011.03835.x.
  3. Chan AW-M, Luk WP, Fung LH, Lee TH. The effectiveness of sublingual immunotherapy for house dust-mite induced allergic rhinitis and its co-morbid conditions. Immunotherapy. 2019;11(16):1387-1897. doi:10.2217/imt-2019-0093.
  4. Sayed KM, Kame AG, Ali AH. One-year evaluation of clinical and immunological efficacy and safety of sublingual versus subcutaneous allergen immunotherapy in allergic conjunctivitis. Graefes Arch Clin Exp Ophthalmol. 2019;257(9):1989-1996. doi:10.2217/imt-2019-0093
  5. Huang Y, Wang C, Cao F, Zhao Y, Lou H, Zhang L. Comparison of long-term efficacy of subcutaneous immunotherapy in pediatric and adult patients with allergic rhinitis. Allergy Asthma Immunol Res. 2019;11(1):68-78. doi:10.4168/aair.2019.11.1.68.
  6. Di Bona D, Plaia A, Leto-Barone MS, La Piana S, Di Lorenzo G. Efficacy of grass pollen allergen sublingnual immunotherapy tablets for seasonal allergic rhinoconjunctivitis: A systematic review and meta-analysis. JAMA Intern Med. 2015;175(8):1301-1309. doi:10.1001/jamainternmed.2015.2840.
  7. Gerstlauer M, Szepfalusi Z, Golden D, Geng B, de Blic J. Real-life safety of 5-grass pollen tablet in 5- to 9-year-old children with allergic rhinoconjunctivitis. Ann Allergy Asthma Immunol. 2019;123(1):70-80. doi:10.1016/j.anai.2019.04.011.
  8. Tabatabaian F, Casale TB. Selection of patients for sublingual immunotherapy (SLIT) versus subcutaneous immunotherapy (SCIT). Allergy Asthma Proc. 2015;36(2):100-104. doi:10.2500/aap.2015.36.3830.
  9. Hsu NM, Reisacher WR. A comparison of attrition rates in patients undergoing sublingual immunotherapy vs subcutaneous immunotherapy. Int Forum Allergy Rhinol. 2012;2(4):280-284. doi:10.1002/alr.21037.