Atopic Keratoconjunctivitis 

Atopic Keratoconjunctivitis – Introduction

• atopic keratoconjunctivitis describes a chronic, inflammatory ocular allergy involving the cornea with potential for serious visual impairment^(1,2)

Types

• Atopic keratoconjunctivitis is a form of allergic conjunctivitis, which also includes^(1,2)
  • Seasonal allergic conjunctivitis
  • Perennial allergic conjunctivitis
  • Vernal keratoconjunctivitis

Epidemiology

Who Is Most Affected

• onset of atopic keratoconjunctivitis typically occurs in late adolescence or early adulthood (mid-20s), but can also develop in first decade of life⁽¹⁾

Incidence/Prevalence

• incidence is probably underreported but thought to be rare in general population⁽²⁾
• among patients presenting to tertiary ophthalmology referral centers, reported prevalence of atopic keratoconjunctivitis is 5%-7% (Clin Exp Allergy 2015 Jun;45(6):1118, Sci Rep 2019 Dec 3;9(1):18205)
• estimated to affect 20%-68% of patients with atopic dermatitis (Am J Clin Dermatol 2019 Dec;20(6):797)

Risk Factors

• risk factors include
  • family history of atopy⁽¹⁾
  • personal history of atopic dermatitis or asthma⁽¹⁾
  • vernal keratoconjunctivitis, which typically resolves during puberty but can persist and evolve into atopic keratoconjunctivitis⁽²⁾
• exposure to higher levels of nitrogen-oxide air pollution associated with increased likelihood of atopic keratoconjunctivitis
  •  based on cross-sectional study
  • web-based survey on allergic ocular disease was sent to 8,500 ophthalmologists (via Japanese Society of Ocular Allergology and Japan Ophthalmologist Association)
  • 3,004 ophthalmologists and family members completed survey (10.8% response rate)
  • respondents reported primary residence and presence of allergic conjunctivitis and other allergic diseases (such as allergic rhinitis, eczema, and asthma)
  • location of respondents’ primary residence was compared to nationwide air pollution survey data (assessing levels of nitric oxide and nitrogen dioxide)
  • atopic keratoconjunctivitis associated with increasing quintile of nitrogen-oxide levels at primary residence
    • nitrogen oxides overall (odds ratio 1.22, p = 0.029)
    • nitric oxide (odds ratio 1.21, p = 0.032)
    • nitrogen dioxide (odds ratio 1.23, p = 0.028)
  • no significant association between prevalence of atopic keratoconjunctivitis and levels of other air pollutants, including oxidants, sulfur dioxide, or particulate matter
  • Reference – Sci Rep 2019 Dec 3;9(1):18205full-text

Associated Conditions

• atopic dermatitis
  • 95% of patients with atopic keratoconjunctivitis reported to have atopic dermatitis; and 20%-68% of patients with atopic dermatitis are reported to have atopic keratoconjunctivitis (Am J Clin Dermatol 2019 Dec;20(6):797)
• food sensitivity or allergy may be associated with atopic keratoconjunctivitis, although association is controversial⁽²⁾
• dry eye is associated with severe and persistent forms of allergic conjunctivitis, including atopic keratoconjunctivitis; see Dry Eye Disease for additional information⁽²⁾

Etiology and Pathogenesis

Causes

• IgE or non-IgE-mediated reaction to allergens⁽²⁾

Pathogenesis

• chronic atopic conjunctivitis is a type IV hypersensitivity immune reaction with predominant T-cell-mediated response^(1,2)
  • in early phase of allergic reaction in allergic conjunctival diseases in general^(1,2)
    • binding of allergen to specific IgE triggers mast cell degranulation
    • mast cell-associated release of preformed mediators, particularly histamine
    • early phase symptoms include eye itching, watery eyes, edema (chemosis) of the eyelid or conjunctiva, and vascular influx (redness)
  • late-phase reaction of hypersensitivity (type IV) characterizes the severe symptoms in atopic keratoconjunctivitis^(1,2)
    • atopic keratoconjunctivitis (AKC) is primarily a Th1 response, in which Th1 cells produce interferon gamma (IFN-gamma), interleukin (IL)-2, and IL-12, which further increase Th1 production, prompting chemotaxis and eosinophil production
    • eosinophilic activation by chemotactic cytokines (chemokines) triggers the release of cytotoxic proteins (such as major basic protein and eosinophilic cationic protein) that damage the corneal epithelium
    • late-phase reaction associated with photophobia, ocular pain, visual impairment, and discharge
  • atopic keratoconjunctivitis characterized by persistent infiltration of eosinophils, lymphocytes, and neutrophils and corresponding pathologic changes to ocular surface
    • transition from connective-tissue to mucosal-type mast cells
    • fibrosis and follicular development
    • disruption of tight junctions between epithelial cells, which is theorized to allow increased allergen exposure and binding of specific IgE molecules and mast cell activation in substantia propria
    • Reference – Ann Allergy Asthma Immunol 2020 Feb;124(2):118
• inflammation in atopic keratoconjunctivitis can be exacerbated by dryness and itching⁽¹⁾

History and Physical

History

Chief Concern (CC)

• ocular itching, redness, tearing, photophobia, ropy or mucus discharge, eye pain, and/or visual disturbance⁽²⁾

History of Present Illness (HPI)

• ask about photophobia, which suggests corneal involvement⁽²⁾
• ask if ocular symptoms are associated with sneezing, nasal discharge, or nasal congestion; presence of vasomotor rhinitis symptoms is more characteristic of seasonal or perennial allergic conjunctivitis than keratoconjunctivitis⁽²⁾
• ask about chronicity
  • chronic course suggests atopic keratoconjunctivitis⁽²⁾
  • intermittent or seasonal symptoms more suggestive of seasonal allergic conjunctivitis; see Allergic Conjunctivitis for additional information^(1,2)
• ask about onset, which typically occurs in late adolescence or early adulthood (mid-20s), but atopic keratoconjunctivitis can also develop in first decade of life⁽¹⁾

Past Medical History (PMH)

• ask about atopic dermatitis⁽²⁾
• ask about atopy⁽²⁾
• ask about asthma⁽¹⁾

Family History (FH)

• ask about family history of atopy⁽¹⁾

Physical

• perform comprehensive eye exam^(1,2)
  • assess eyelids and periorbital skin for hyperpigmentation, eczema, meibomitis, and blepharitis
  • evert upper eyelid to assess palpebral conjunctival mucosa for tarsal papillae or fibrosis using slit lamp (ophthalmoscope may be used if slit lamp is unavailable, such as non-ophthalmologists/optometrists)
  • perform slit-lamp exam to assess for findings suggestive of limbal or corneal involvement
    • signs of limbal involvement include limbal ring edema and/or Trantas dots
    • corneal involvement includes superficial punctate keratitis, corneal ulcer or opacity, vernal plaque, or neovascularization
  • ocular surface staining procedures can identify damage to corneal epithelium
    • fluorescein staining, viewed under cobalt-blue filter, can identify corneal epithelial surface defects
    • other less frequently used staining procedures include
      • rose bengal, which stains mucous particles, strands, filaments, and plaques more vividly than fluorescein but can cause stinging sensation
      • lissamine green, which fades quickly
    • Reference – Ann Allergy Asthma Immunol 2020 Feb;124(2):118
  • additional testing may include tear-film evaluation

Diagnosis

Making the Diagnosis

• diagnosis is based on patient history and physical findings
• diagnosis involves close collaboration between ophthalmologist and allergist⁽²⁾
  • ophthalmologist can provide accurate diagnosis based on slit-lamp exam findings suggesting corneal involvement and additional testing to identify any associated ocular conditions or complications
  • allergist can perform comprehensive allergy assessment and confirm relevance of any sensitivities in ocular allergic disease

Differential Diagnosis

• other allergic conjunctival diseases to consider include
  • vernal keratoconjunctivitis (VKC)
    • VKC is characterized by proliferative changes in the tarsal or limbal conjunctiva, including papillary hyperplasia of palpebral conjunctiva and/or swelling or limbal gelatinous hyperplasia
    • VKC is associated with exacerbations during springtime and in hot and dry climates
    • typical onset of VKC is in first decade of life with resolution during puberty; however, VKC is reported to persist into adulthood in < 3% of patients, complicating the distinction between VKC and atopic keratoconjunctivitis in some cases
  • seasonal or perennial conjunctivitis (allergic conjunctival disease without proliferative changes); see Allergic Conjunctivitis for additional information
  • papillary conjunctivitis (caused by repetitive mechanical irritation, most commonly with contact lens wear); see Papillary Conjunctivitis in Complications Related to Contact Lens Wear for additional information
  • References – Allergol Int 2020 Jul;69(3):346full-text, Cochrane Database Syst Rev 2020 Oct 21;10:CD013298full-text, Curr Opin Allergy Clin Immunol 2020 Oct;20(5):501
• other diagnoses to consider include⁽¹⁾
  • severe blepharitis
  • ocular rosacea
  • other causes of conjunctival scarring, including ocular cicatricial pemphigoid
  • Stevens-Johnson syndrome
  • graft-versus-host disease
  • prior ocular chemical injury
  • infectious conjunctivitis
  • toxic conjunctivitis
  • phlyctenular conjunctivitis
  • limbal stem-cell deficiency
  • dry eye disease
  • scleritis or episcleritis

Testing Overview

• perform comprehensive allergy testing
  • perform skin prick testing as initial investigation
  • additional allergen testing may be indicated
    • conjunctival allergen provocation testing may be needed if patient is polysensitized, if relationship between sensitization and symptoms is unclear, or if skin prick tests are negative despite strong clinical suspicion of allergen involvement
    • patch testing may be considered if patient has eczematous blepharitis or blepharo-conjunctivitis and chemical sensitizer is suspected
  • allergen investigation in atopic keratoconjunctivitis involves assessment of both IgE‐mediated and non‐IgE‐mediated hypersensitivity⁽²⁾; see also
    • Diagnosis and Evaluation of IgE-mediated Allergies
    • Diagnosis and Evaluation of Non-IgE- and Mixed-IgE-mediated Allergies
• additional ophthalmic testing may be indicated, including tear-film evaluations to test for dry eye or other lacrimal dysfunction

Allergy Testing

Skin Prick and Patch Testing

• skin prick testing is the initial investigation for allergen sensitization⁽²⁾
  • perform skin prick testing for standard panel of allergens and any suspected allergens identified based on thorough history-taking⁽²⁾
  • skin prick testing is highly sensitive for systemic allergies but may not identify an allergic sensitization that is limited to the ocular surface (for which conjunctival allergen provocation testing may be needed)
• patch testing
  •  may be useful in patients with eczematous blepharitis or blepharo-conjunctivitis, which suggests possible delayed type reaction to chemical sensitizer
  • involves applying potential chemical sensitizers in aluminum or cellulose disk to patient’s back for 48 hours and observing at various time points
  • common chemical sensitizers include preservatives in ophthalmic or contact lens solutions, such as benzalkonium chloride and thimerosal
  • interpret results with understanding that periorbital skin differs from the back, due to differing amount of sunlight exposure, epithelial and dermal depth, and number of mast cells
  • Reference – Ann Allergy Asthma Immunol 2020 Feb;124(2):118

Conjunctival Allergen Provocation Test

• conjunctival allergen provocation test (CAPT), also called conjunctival allergen challenge, can confirm specific allergen hypersensitivity that is limited to ocular surface without systemic sensitization (Ann Allergy Asthma Immunol 2020 Feb;124(2):118)
• perform CAPT if patient is polysensitized, if relationship between sensitization and symptoms is unclear, or if skin prick tests are negative despite strong clinical suspicion of allergen involvement⁽²⁾
• CAPT involves instilling suspected allergen on the ocular surface
  • observe for allergic response (redness, chemosis, lid swelling, itching, or tearing) at 15-30 minutes after instillation
  • late-phase inflammatory reactions are also possible
  • Reference – Ann Allergy Asthma Immunol 2020 Feb;124(2):118
• before performing CAPT, discontinue medications that could affect results⁽²⁾
  • discontinue topical ophthalmic medications 48 hours prior
  • discontinue systemic antihistamines 2 weeks prior
• perform CAPT in hospital if patient has a severe form of ocular allergy, including atopic keratoconjunctivitis⁽²⁾
• CAPT is considered safe (systemic side effects, such as generalized itching, bronchospasm, and anaphylaxis, are reportedly rare) (Ann Allergy Asthma Immunol 2020 Feb;124(2):118)

Other Allergy Testing

• perform serum-specific IgE measurements if skin prick test results are discordant with medical history or contraindicated (Ann Allergy Asthma Immunol 2020 Feb;124(2):118)
• in severe forms of ocular allergy, including atopic keratoconjunctivitis, investigate both IgE‐mediated and non‐IgE‐mediated hypersensitivity⁽²⁾; see also
  • Diagnosis and Evaluation of IgE-mediated Allergies
  • Diagnosis and Evaluation of Non-IgE- and Mixed-IgE-mediated Allergies
• consider testing for food sensitization, although association of food allergies with ocular surface disease is controversial⁽²⁾
  • if assessment for food sensitization is weakly positive but CAPT is strongly positive, consider association with ocular disease to be positive if either
    • wheal skin size is larger than half of the positive histamine control test
    • specific serum IgE > 0.1 units/mL

Other Diagnostic Testing

• evaluation of tear film can help identify associated tear-film dysfunction
  • assess tear osmolarity to identify hyperosmolarity, which suggests a form of dry eye disease
  • Schirmer tear test can assess for inadequate tear production
    • Schirmer I (without anesthesia) measure both basal and reflex tearing (≤ 5 mm of wetting after 5 minutes considered abnormal)
    • Schirmer II test (with anesthesia) measures only basal tearing (≤ 3 mm of wetting after 5 minutes considered abnormal)
  • Reference – Ann Allergy Asthma Immunol 2020 Feb;124(2):118

Management

Management Overview

• first-line management involves identification and avoidance of allergic triggers, if possible, as well as other protective measures such as wearing protective glasses
• symptomatic interventions may include application of cold compress, eye wash, or artificial tears
• calcineurin inhibitors may improve symptoms and reduce severity of clinical findings associated with atopic keratoconjunctivitis, but evidence on long-term safety and efficacy remains limited
• topical ophthalmic corticosteroids are often used to treat acute flare-ups, but long-term steroid use is associated with serious ocular complications, including cataract formation and glaucoma⁽²⁾
• patients with severe atopic keratoconjunctivitis may benefit from psychological care and individualized support, especially if symptoms interfere with daily activities such as school or work⁽²⁾

Irritant Avoidance and Other Protective Measures

• first-line management includes identification and avoidance of any allergens/irritants, but this can be difficult for many patients with atopic keratoconjunctivitis due to large number and variety of triggers^(1,2)
• other protective measures include⁽²⁾
  • limiting exposure to nonspecific irritants, such as tobacco smoke and pollutants
  • wearing protective glasses
  • protecting eyes against ultraviolet light
  • avoiding contact lenses and facial cosmetics as much as possible

Symptomatic and Supportive Measures

• application of cold compress to the eyelids can provide some symptom relief⁽²⁾
• saline solution eye wash can remove allergens and dilute cytokines on ocular surface⁽²⁾
• application of artificial tears⁽²⁾
  • preferably without preservatives, can also enhance barrier function of conjunctiva, dilute allergens, and reduce itchiness
  • FDA warns consumers not to use eye drops from several major brands due to the potential risk of eye infections that could result in vision loss or blindness (FDA 2023 Oct 30)
  • United States Centers for Disease Control and Prevention (CDC) and FDA recommend ceasing use of EzriCare and Delsam Pharma’s artificial tear products after outbreak of extensively drug-resistant Pseudomonas aeruginosa infection reported in United States (CDC Healthcare Associated Infections Outbreak and Patient Notifications 2023 Mar 21)
• patients with severe atopic keratoconjunctivitis may benefit from psychological care and individualized support, especially if symptoms interfere with daily activities such as school or work⁽²⁾

Calcineurin Inhibitors

• calcineurin inhibitors, particularly cyclosporine and tacrolimus, are reported to modulate T-cell function and improve ocular symptoms in atopic keratoconjunctivitis⁽¹⁾
• safety profile of topical ophthalmic calcineurin inhibitors
  • common side effects include ocular burning and discomfort upon distillation
  • some cases of suspected bacterial or viral infection of the ocular surface, including herpes simplex keratitis, have been reported with calcineurin inhibitor use
  • calcineurin inhibitors provide a potentially safer alternative to long-term use of topical ophthalmic corticosteroids, which are associated with more serious adverse effects
  • Reference – Expert Opin Drug Metab Toxicol 2014 Apr;10(4):543
• efficacy of topical ophthalmic cyclosporine
  • topical ophthalmic cyclosporine drops might improve ocular signs and symptoms in patients with atopic keratoconjunctivitis (level 2 [mid-level] evidence)
    •  based on Cochrane review of small randomized trials
    • systematic review of 3 randomized trials evaluating topical ophthalmic cyclosporine A drops in 58 patients with atopic keratoconjunctivitis
    • meta-analysis not performed due to heterogeneity of dosing, controls, and follow-up duration
    • 1 trial compared cyclosporine A 0.05% to preservative-free artificial tears (1 drop 6 times daily for 2 weeks and then 4 times daily for 2 weeks) in 22 patients with atopic keratoconjunctivitis; comparing cyclosporine vs. preservative-free artificial tears at 4 weeks
      •  improvement in 15-point composite symptom score, 4 points vs. 0.5 points (p = 0.048)
      • improvements in median 4-point score for severity of clinical signs, including
        • bulbar conjunctival hyperemia, 1 point vs. 0.5 points (p = 0.017)
        • upper tarsal conjunctival papillae, 1.5 points vs. 0 points (p = 0.005)
        • punctate keratitis, 2.5 points vs. -0.5 points (p = 0.007)
    • 1 trial compared cyclosporine A 0.05% vs. placebo (vehicle) 1 drop 4 times daily in 18 patients with atopic keratoconjunctivitis; comparing cyclosporine vs. control at 3 months, no significant differences in symptom scores or severity of clinical signs
    • 1 trial compared cyclosporine 2% in maize oil vs. maize oil alone (4 times daily) in 21 patients with atopic keratoconjunctivitis; comparing cyclosporine vs. maize oil at 3 months
      • improvement in symptom scores from baseline, 5.1 points vs. 1.8 points (no p value reported)
      • improvement in composite score for severity of clinical signs, 14 points vs. 1.5 points (p = 0.02)
      • mean reduction in weekly topical ophthalmic steroid drop usage, 85.5 drops vs. 13.9 drops (p = 0.005)
    • no serious adverse effects reported
    • Reference – Cochrane Database Syst Rev 2012 Sep 12;(9):CD009078
  • for additional evidence on topical ophthalmic cyclosporine for keratoconjunctivitis, see Vernal Keratoconjunctivitis
• efficacy of topical ophthalmic tacrolimus
  • topical ophthalmic tacrolimus and corticosteroids might similarly improve eye discomfort in adults with atopic keratoconjunctivitis (level 2 [mid-level] evidence)
    •  based on small cross-over randomized trial
    • 25 adults with atopic keratoconjunctivitis were randomized to topical ophthalmic tacrolimus 0.1% ointment vs. clobetasone butyrate 0.05% twice daily for 3 weeks and then were crossed over to other medication after 2-week washout period
    • no other topical, periorbital, or systemic anti-inflammatory or anti-infective medication was allowed during study or washout periods
    • patients rated eye discomfort on 0- to 10-point scale (with higher scores indicating more severe discomfort)
    • 20 adults (80%) completed study and were included in analysis
    • comparing tacrolimus vs. clobetasone butyrate
      • improvement in patient-reported eye discomfort -2.13 points vs. -1.86 points (not significant)
      • no significant differences in intraocular pressure or clinical findings, including eczema, blepharitis, conjunctivitis, and keratitis
    • no patients discontinued trial due to adverse effects
    • Reference – Eye (Lond) 2007 Jul;21(7):968
  • topical ophthalmic tacrolimus ointment reported to improve ocular signs and symptoms in adults with refractory, steroid-dependent atopic keratoconjunctivitis (level 3 [lacking direct] evidence)
    •  based on case series
    • 11 adults (mean age 32 years) with refractory, steroid-dependent atopic keratoconjunctivitis were treated with tacrolimus 0.1% topical ophthalmic ointment and followed for mean 4.5 years
    • patients discontinued all other medications, including topical ophthalmic or systemic immunosuppressive agents, 1 week prior to initiating tacrolimus therapy
    • various signs and symptoms were graded on 4-point scale (with 0 points indicating absence and 3 points indicating greatest severity)
    • patients applied topical ophthalmic tacrolimus 0.1% ointment into inferior conjunctival fornix of each eye, with starting dose varying based on severity of atopic keratoconjunctivitis:
      • for severe atopic keratoconjunctivitis: once daily for 1 week, once every other day for 1 week, twice weekly for 1 week, and once weekly thereafter
      • for moderate atopic keratoconjunctivitis: once every other day for 1 week, twice weekly for 1 week, and once weekly thereafter
      • for mild atopic keratoconjunctivitis: twice weekly for 1 week and then once weekly thereafter
    • comparing baseline vs. last follow-up, mean severity scores for the following signs and symptoms (no p values reported)
      • itching, 2.25 points vs. 0.25 points
      • redness, 2.25 vs. 0.2 points
      • foreign body sensation, 2 points vs. 0.3 points
      • hyperemia, 2.25 points vs. 0.5 points
      • lid thickening, 2.2 points vs. 0.4 points
      • papillae, 2 points vs. 0.25 points
      • superficial punctate keratopathy, 2 points vs. 0 points
    • all patients reported mild burning sensation with tacrolimus application, but none discontinued medication due to adverse effects, and no serious drug-related ocular complications were reported
    • Reference – Am J Ophthalmol 2014 Feb;157(2):280
  • topical ophthalmic tacrolimus ointment reported to improve ocular symptoms in children with steroid-dependent atopic or vernal keratoconjunctivitis (level 3 [lacking direct] evidence)
    •  based on case series
    • 33 children aged 7-16 years (mean age 12 years, 70% male) with severe bilateral atopic or vernal keratoconjunctivitis refractory to conventional ophthalmic topical medications were treated with topical ophthalmic tacrolimus 0.03% ointment twice daily
      • patients also instilled ophthalmic olopatadine hydrochloride 0.2% once daily (beginning ≥ 1 month before initiating tacrolimus therapy) and ocular lubricant containing polyethylene glycol 4 times daily
      • topical ophthalmic corticosteroid therapy was discontinued before tacrolimus initiation and then resumed for several days as needed with fast taper
    • 24 children had vernal keratoconjunctivitis (76%) and 8 children at atopic keratoconjunctivitis (24%)
    • mean follow-up duration 13 months (range 12-29 months)
    • resolution of ocular allergy symptoms and controlled disease reported in 20 children (61%)
    • 5 children (15%) discontinued tacrolimus therapy because of adverse effects, including ocular irritation and burning (4 children) and herpetic keratitis (1 child)
    • Reference – Arq Bras Oftalmol 2017 Jul;80(4):211

Corticosteroids

• topical ophthalmic corticosteroids can be used to manage acute exacerbations, but long-term use is discouraged due to risks of increased intraocular pressure and cataract formation^(1,2)
  • in cases with high symptomatic score, ophthalmologist can prescribe topical ophthalmic corticosteroids with close follow-up
  • steroid courses are often short and rapidly tapered
  • strong short-term efficacy of steroids is balanced by long-term risks of iatrogenic complications such as cataract and glaucoma

Other Medications

• many agents that are commonly effective for seasonal and perennial allergic conjunctivitis, including topical ophthalmic antihistamines and mast-cell stabilizers (such as lodoxamide, nedocromil sodium, or pemirolast), are reportedly ineffective in atopic keratoconjunctivitis⁽¹⁾
• advise against long-term use of topical ophthalmic vasoconstrictors due to potential rebound effect that can produce persistent red eye after discontinuation (Allergy Rhinol (Providence) 2016 Jan;7(2):107)
• systemic treatments reported to improve ocular symptoms in patients with severe atopic keratoconjunctivitis, but evidence is limited to case reports
  • omalizumab 300 mg subcutaneously twice monthly reported to improve conjunctivitis and ocular pain and reduce corticosteroid use in 35-year-old male patient with severe atopic keratoconjunctivitis (BMJ Case Rep 2010 Oct 28;2010:doi:10.1136/bcr.04.2010.2919full-text)
  • low-dose systemic tacrolimus (started at dose of 0.03-0.08 mg/kg and titrated based on symptom response and blood trough levels) reported to improve ocular symptoms in 3 adults with severe, refractory atopic keratoconjunctivitis in case series; adverse effects included minor cramping, paresthesia, and difficulty concentrating (Cornea 2006 Dec;25(10):1147)
  • no randomized trials evaluating systemic treatments (including corticosteroids, nonsteroidal anti-inflammatory drugs, immunomodulators, or monoclonal antibodies) identified in Cochrane review of patients ≥ 16 years old with severe atopic keratoconjunctivitis (Cochrane Database Syst Rev 2020 Oct 21;10:CD013298)
• subcutaneous allergen-specific immunotherapy reported to improve ocular signs and symptoms and allow for discontinuation of oral corticosteroids in case report of 22-year-old woman with atopic keratoconjunctivitis refractory to conventional topical ophthalmic agents (Case Rep Ophthalmol 2017 Sep;8(3):562full-text)
• reported management strategies for dupilumab-associated atopic keratoconjunctivitis include symptomatic topical ophthalmic corticosteroid and antihistamine eye drops or discontinuation of dupilumab
  • based on small case series
  • 3 patients started dupilumab for atopic dermatitis and developed ocular symptoms 1 day to 6 weeks after initial dupilumab treatment
  • ocular symptoms included blurry vision, foreign body sensation, itching, light sensitivity, redness, and tearing
  • all 3 patients had findings of atopic keratoconjunctivitis including papillae with epithelial infiltrates at the corneoscleral limbus (in all 3 patients), subepithelial corneal infiltrates (2), mucoid discharge (1), conjunctival pseudomembranes (1), and corneal epithelial defects (1)
  • 1 patient continued with dupilumab but had regular recurrences of ocular allergic symptoms that were managed with topical ophthalmic corticosteroid and antihistamine eye drops
  • 2 patients stopped using dupilumab due to severe ocular symptoms
  • Reference – J Am Acad Dermatol 2021 Jul;85(1):265

Surgery and Procedures

• in severe cases, interventions such as supratarsal steroid injection or amniotic membrane graft to heal corneal ulcer may be needed⁽²⁾

Consultation and Referral

• management of atopic keratoconjunctivitis requires close collaboration between ophthalmologist and allergist⁽²⁾

Complications

• complications of atopic keratoconjunctivitis include^(1,2)
  • cataract formation, particularly anterior subcapsular cataracts (typically developing 10 years after disease onset); see Cataracts in Adults for additional information
  • blepharitis
  • glaucoma (possibly due to long-term ophthalmic topical steroid use)
  • retinal detachment (thought to be secondary to chronic eye rubbing)
  • keratoconus (associated with atopy but may also be exacerbated by chronic eye rubbing)
  • uveitis
  • increased susceptibility to infectious keratitis, particularly with Staphylococcus aureus or herpes simplex; see also Keratitis or Herpes Simplex Keratitis
  • tarsal fibrosis
  • symblepharon

Prognosis

• atopic keratoconjunctivitis does not typically self-resolve and requires ongoing management (Cochrane Database Syst Rev 2012 Sep 12;(9):CD009078)

Prevention and Screening

• not applicable

Guidelines and Resources

Guidelines

United Kingdom Guidelines

• College of Optometrists clinical management guideline on atopic keratoconjunctivitis can be found at College of Optometrists 2021 Aug 06

European Guidelines

• European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Ocular Allergy (IGOA) guideline on conjunctival allergen provocation testing can be found in Allergy 2017 Jan;72(1):43

Asian Guidelines

• Japanese Society of Allergology/Japanese Society of Ocular Allergology guideline on allergic conjunctival diseases can be found in Allergol Int 2020 Jul;69(3):346full-text

Review Articles

• review of diagnosis and management of allergic conjunctivitis can be found in Ann Allergy Asthma Immunol 2020 Feb;124(2):118
• review of diagnosing and managing allergic conjunctivitis in childhood can be found in Pediatr Allergy Immunol 2019 Jun;30(4):405
• review of ocular involvement in atopic disease can be found in Curr Opin Ophthalmol 2018 Nov;29(6):576
• review of atopic keratoconjunctivitis can be found in J Am Acad Dermatol 2014 Mar;70(3):569

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References

General References Used

The references listed below are used in this DynaMed topic primarily to support background information and for guidance where evidence summaries are not felt to be necessary. Most references are incorporated within the text along with the evidence summaries.

1. Patel N, Venkateswaran N, Wang Z, Galor A. Ocular involvement in atopic disease: a review. Curr Opin Ophthalmol. 2018 Nov;29(6):576-581.
2. Fauquert JL. Diagnosing and managing allergic conjunctivitis in childhood: The allergist’s perspective. Pediatr Allergy Immunol. 2019 Jun;30(4):405-414.