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.6 to 2.0 mm, increased IOP inapproximately 30% of patients treated for 3 weeks or more, posterior subcapsular cataract formation that will not progress if corticosteroids arediscontinued, bacterial or fungal superinfection secondary to suppression of cellular defense systems, and decreased wound healing.b.Systemic and repeated periocular therapy.Complications of systemic or repeated periocular therapy are all of those described above, plusextraocular muscle fibrosis (periocular injection), Cushing syndrome, peptic ulcers, systemic hypertension, sodium retention, hyperglycemia indiabetics, psychosis, failure of growth, amenorrhea, aseptic joint necrosis, osteoporosis, myopathy, fluid retention, and Addison's disease.B.Mydriatic cycloplegics are used to give comfort by relieving iris sphincter and ciliary muscle spasm and to prevent scarring between the pupillary borderand anterior lens capsule (posterior synechiae).Atropine, the strongest mydriatic cycloplegic, is used in strengths of 1%.It should be reserved formoderately severe to severe anterior uveitis and should be used one to two times daily.As uveitis lessens, the atropine dosage may be reduced or the patient placed on homatropine 5% at bedtime.For mild to moderate anterior uveitis, homatropine 5% qd to bid will suffice to move the pupil.Bedtime use isbeneficial only in milder cases, because the pupil is mobilized primarily during sleep and iatrogenic presbyopia is not present during the day.Eyes withpupils that fail to dilate on atropine should have the lids taped shut between applications to increase the effect of the atropine.Phenylephrine 2.5% bid to tid(in the absence of significant cardiovascular disease) and cocaine 4% drops q30min tid are also useful in mobilizing the otherwise scarred-down pupil.Atropine may also complicate or precipitate urinary retention in patients with prostatism.Scopolamine 0.25% has almost the same cycloplegic strength asatropine and may be substituted in patients with urinary retention problems.Scopolamine itself, however, in very frequent doses may also aggravate thiscondition.Cyclopentolate may aggravate iritis because of its neutrophilic chemotactic effect; however, this has not been proven true in clinical experience.C.NSAIDs.Oral NSAIDs appear to act by blocking local mediators of the inflammatory response such as the polypeptides of the kinin system, lysosomalenzymes, lymphokines, and prostaglandins.The prostaglandins are one of the many chemical mediators involved in the pathogenesis of uveitis; they aresynthesized by the enzyme prostaglandin synthetase and found in all tissues of the eye.Prostaglandins cause a marked increase in protein content of theaqueous humor and mild smooth muscle contraction (pupillary miosis).Certain prostaglandins lower IOP, and others (E and E2) may increase it.The1increased permeability of the ciliary epithelium may be a critical factor in inducing increased IOP secondary to prostaglandin release.All should be takenwith meals.1.Indications.There is no evidence that any NSAID is effective when used as the primary agent in therapy of intraocular inflammation, but they are oftensteroid-sparing agents.They are, however, useful in long-term therapy of recurrent anterior uveitis, rheumatoid scleritis, or macular edema initiallycontrolled by steroid therapy.Diflunisal (Dolobid) 250 to 500 mg p.o.bid, diclotenac (voltaren 50 mg p.o.bid), naproxen (Naprosyn) 250 or 375 mg p.o.bid, or indomethacin (Indocin SR) 75 mg p.o.qd to bid, may allow a patient to reduce or even discontinue steroid therapy without reactivation of disease.Rofecoxib (Vioxx) 25 mg p.o.qd and celecoxib (Celebrex) 100 to 200 mg p.o.bid are in a new class of NSAID that selectively inhibits cyclooxygenase-2and reduces prostaglandin synthesis (COX-2 inhibitor) and are better tolerated, causing less gastrointestinal discomfort.Their efficacy in the treatment ofuveitis and CME is still under investigation.2.Salicylates are effective in reducing inflammatory response and protein increase in the anterior chamber after keratocentesis.Aspirin must be used in therange of 4 to 5 g or more per day to be effective, and may be given in several divided doses.3.Toxicity includes gastric mucosal ulceration and liver and renal damage.Urine, stool, and blood monitoring should be done every few months.COX-2inhibitors should be avoided in patients with liver disease and when used, liver function tests should be performed.4.Topical NSAIDs are equivocally effective in iritis but may have a steroid-sparing effect.They may also be successful in treatment of CME.Currentagents include flurbiprofen 0.03% (Ocufen), suprofen 1% (Profenal), diclofenac 0.1% (Voltaren), and ketorolac 0.5% (Acular), the last three drugs indosages of three to four drops per day for CME (see Appendix A for U.S.Food and Drug Administration [FDA]-approved use).D.Immunosuppressive agents.Immunosuppressive drugs usually should not be prescribed by an ophthalmologist alone, but in concert with an oncologist orhematologist who is familiar with them and confident in their management.In making a decision as to which patient should receive immunosuppressivetherapy, the physician must remember that the use of these drugs for nonneoplastic and non-life-threatening illness is a great clinical responsibility.To datethere appear to have been very few severe complications from the combined regimen of corticosteroids and immunosuppressive agents, probably because ofthe lower dosages used and the better general health of the ophthalmic patients receiving them.Patients should be fully informed as to potential risks andbenefits.A signed consent form or chart note to that effect is advisable.1.Selection of patients involves choosing those who:a.Have Wegener's granulomatosis, polyarteritis nodosa, or Behçet's disease (immunosuppressive agents are the drugs of first choice).b.Failed to respond to conventional corticosteroid therapy or have an unacceptable side effect from the drugs.c.Have progressive, usually bilateral vision-threatening disease.d.Have adequate follow-up.e.Are reliable about following instructions.f.Are willing to undergo therapy with full knowledge of the possible deleterious side effects.g.May potentially benefit from the use of the drugs.h.Have no unequivocal contraindication such as active TBC, toxoplasmosis, or other infectious process.2.Three classes of immunosuppressive agents are used in ocular inflammatory disease: alkylating agents, antimetabolites, and antibiotics.a.The alkylating agents cyclophosphamide and chlorambucil work by suppression of lymphocyte T-cell (cell-mediated immunity) and, to a lesserextent, B-cell (antibodies) function.1.Clinical indications are most commonly Behçet's disease, sympathetic ophthalmia, Wegener granulomatosis, rheumatoid arthritis, polyarteritisnodosa, relapsing polychondritis, severe systemic lupus erythematosus, bullous pemphigoid, and malignancy.These medications can inducelong-term remission in some patients with severe uveitis.2.Cyclophosphamide dosage in adult patients starts at 150 to 200 mg per day (1 mg/kg/day) taken on an empty stomach, in the morning and9followed with hydration of 3 L of fluid daily.The aim of the therapy is to lower the lymphocyte count to 1.0 × 10 per L (normal 1.3 to 3.5 × 109 per9L).The total white cell count should not fall below 3.5 × 10 per L.The white cell count and differential are obtained at baseline and then followedtwice weekly for the first 2 to 3 weeks
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