Page 670 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 47 Allergic Disorders of the Eye 643

recommended, especially for long-term use, due to rebound that several cell-mediated processes are involved and contribute
vasodilatation of the conjunctival vessels with long-term vaso- to the chronic inflammation found in PAC. 7
constrictor use. They can cause contact allergic conjunctivitis,
sedation, or excitability, and they are slower and shorter-acting Therapy
than high-potency topical antihistamines. In the case of house dust mite sensitivity, advice should be
provided on mite reduction; allergy support groups can be helpful
for this and for accessing equipment. Potential mite reduction
CLiNiCaL PEarLS measures include removing soft furnishings (e.g., carpet, curtains)
Seasonal Allergic Conjunctivitis from the bedroom; using special vacuum cleaner filters; intensive
and regular vacuuming of bedrooms, including the curtains and
• Seasonal response to allergen (e.g., pollen) mattress; using a mite-impermeable mattress and pillow covers;
• Mast cell–mediated washing bed linen and curtains at mitocidal temperatures (>131
• Antihistamines, mast cell inhibitors
°F or >55 °C); and using mitocidal chemicals. For mold sensitivity,
dehumidifying devices and mold-killing chemicals may help.
Of the several topical nonsteroidal antiinflammatory drugs The drug therapy of PAC is essentially as recommended for
(NSAIDs) assessed in ocular allergy, ketorolac is the only one SAC (see above), but as the disease is usually prolonged, the
approved for ocular allergy. NSAIDs are not used as first-line continuing use of mast cell inhibitors assumes more importance,
therapy for ocular allergy. They offer the advantage of safety, whereas antihistamines tend to be used intermittently for flare-ups
but their efficacy is not well proven against other established of inflammation.
remedies, and cost is a concern, as is discomfort upon instillation Allergen-specific immunotherapy (AIT) can be effective for
and potentially reduced patient adherence. The use of NSAIDs patients with severe allergic rhinoconjunctivitis who have specific
is more common outside the United Kingdom. IgE antibodies to allergens (Chapter 91). Increasing doses of the
Topical steroids have a minimal role in SAC because of allergen are administered by subcutaneous immunotherapy
their potential for ocular adverse effects (see below). They (SCIT) or sublingual immunotherapy to achieve hyposensitization
occasionally are used short-term for severe disease to gain control mediated by production of interleukin (IL)-10 and transforming
of inflammation, but their use must be supervised by an growth factor (TGF)-β1. Side effects, including anaphylaxis, are
ophthalmologist. known to occur with this form of therapy. SIT requires a long-term
commitment from the patient and/or caregiver in terms of time
PERENNIAL ALLERGIC CONJUNCTIVITIS (SCIT requires monthly injections for 3 years) and expense. This
may not be practical for the SAC or PAC patient who does not
PAC is the second most common ocular allergy. It bears many suffer from other comorbidities. 8
similarities to SAC, but because the allergens in PAC are present
for most or all of the year, the time course of the disease is not Experimental Models of Allergic Conjunctivitis
seasonal. The disorder is again most severe and most frequently Conjunctival Allergen Challenge
seen in children and young adults. House dust mite (Derma- This model involves challenging the ocular surface with an allergen
tophagoides pteronyssinus) is the most common sensitizing allergen, to artificially provoke an ocular allergic response in sensitized
9
but animal hair and dander, molds, and other antigens may be individuals. Symptoms are similar to those seen in SAC, and
responsible. so the model is useful for investigating the early- and late-phase
The symptoms are perennial ocular itch, discomfort, watering, allergic responses at the ocular surface. During the early-phase
redness, and some discharge. Patients may be able to correlate response (20 mins post challenge), increased levels of histamine
symptomatology with exposure to, for example, pets or a par- and tryptase can be detected in tears, suggesting that the active
ticular location. House dust mite allergy sufferers may give a cell population is predominantly mast cells. At 6 hours, histamine
history of symptoms worse in the morning. Approximately and eosinophil cationic protein levels are increased, but not
one-third have an associated rhinitis, and a family and/or personal tryptase, suggesting that basophils and eosinophils are infiltrating
10
atopic history is very common. The clinical appearance is of and active during the late phase. T cells are also increased and
mild conjunctival inflammation, and clinical signs may be very can be seen in bulbar biopsy specimens. The allergen challenge
slight. The bulbar conjunctiva (on the eye globe) may be slightly model is often used for testing the efficacy of eye drops.
red and edematous, and the tarsal conjunctiva shows mild to
moderate hyperemia, infiltration, and fine papillae. Lid edema Experimental Allergic Conjunctivitis
11
is usually mild. As with SAC, there is neither conjunctival scarring A mouse model of experimental allergic conjunctivitis (EAC)
nor corneal or serious limbal involvement, so normal visual was established by an initial footpad sensitization with short
acuity is maintained. ragweed pollen (SRW), followed 7–10 days later by conjunctival
SRW challenge. An infiltration of mast cells, neutrophils, and
Immunohistological Studies in PAC eosinophils occurs, as well as increased conjunctival chemosis
As with SAC, PAC involves an immediate-type hypersensitivity and lid edema. Interestingly, although there is no significant
response, but because the allergens are present continuously, the infiltration of T cells, expression of the model is attenuated in
resultant inflammation is more chronic. Therefore the immu- IL-12 knock-out mice. In BALB/c mice, SRW-induced EAC was
nopathology of PAC differs slightly from that of SAC. Increased interferon (IFN)-γ–dependent and could not be induced in IFN-γ
12
numbers of mast cells are detected in both the tarsal conjunctival knock-out mice, supporting a role for Th1 pathways. A role
epithelium and the substantia propria, with both mucosal and for thymic stromal lymphopoietin (TSLP) has also been dem-
2
connective-tissue-type mast cell phenotypes. In addition, mast onstrated in EAC, with TSLP expression upregulated in allergen-
cells, eosinophils, neutrophils, and T cells are present, suggesting challenged corneal and conjunctival epithelium. 13