Retinal inflammation

This reference studies the most recent advances in the development of ocular drug delivery systems. Covering methods to treat or prevent ocular inflammation, retinal vascular disease, retinal degeneration, and proliferative eye disease, this source covers breakthroughs in the management of endophthalmitis, uveitis, diabetic macular edema, and age-related macular degeneration. 

VEGF antagonists Adverse reactions to intravitreal VEGF antagonists include endophthalmitis, intraocular inflammation, retinal detachment, and possibly cataract or cataract progression. It has also been suggested that there may be an increased risk of stroke [55 ]. 

Joffre, C, Leclere, L, Buteau, B, Martine, L, Cabaret, S, Malvitte, L, Acar, N, Lizard, G, Bron, A, and Creuzot-Garcher, C, 2007. Oxysterols induced inflammation and oxidation in primary porcine retinal pigment epithelial cells. Curr Eye Res 32, 271-280. 

Initial clinical assessment involved some 1200 wet AMD patients. Although both control and product groups continued to experience vision loss, the rate of vision decline experienced by macugen-treated patients was significantly slower than in the case of control patients. The most frequent/potentially serious side effects noted during these trials were endophthalmitis, retinal detachment, eye inflammation/irritation and blurred vision, although rare cases of anaphylaxis have also been reported. Macugen is marketed by Eyetech Pharmaceuticals and Pfizer. 

Currently, there is only one antisense drug on the market— Vitravene (active ingredient fomivirsen) for the treatment of cytomegalovirus (CMV)-induced retinitis (inflammation of the retina) in AIDS patients. Fomivirsen has 21 nucleotides complementary to a CMV mRNA sequence, which is necessary for the production of infectious virus. Two examples of experimental antisense drugs are provided in Exhibit 3.15, while Table 3.1 lists other antisense drugs in clinical phase. 

Inhibitors of IkBo phosphorylation have been described which irreversibly inhibit cytokine-induced phosphorylation without affecting constitutive phosphorylation. One such compound (Bay 11-7083 ((E)3-[4-f-butylphenyl)-sulfonyl]-2-propenenitrile)) was found to be effective in two animal models of inflammation after intraperitoneal administration [89]. In addition to the effect it has on the expression of adhesion molecules in pro-inflammatory responses, inhibition of the transcription factor NFkB will also have an effect on angiogenesis. Endothelial cells can produce growth factors and cytokines which have pro-angiogenic effects. Some of these factors, e.g. IL-8, TNFa and MCP-1 are known to be produced via NFkB-mediated endothelial cell activation [90,91]. The importance of NFKB-mediated responses in pro-angiogenic endothelium was reflected in studies in which the NFkB inhibitor PDTC decreased retinal neovascularization in the eye of mice [92]. 

Uses Neovascular wet macular degenoation Action Vascular endothelial growth factor inhibitor Dose 0.5 mg intravitreal inj qmo Caution [C ] Hx thromboembohsm Contra Periocular Infxn Disp Inj SE Endophthalmitis, retinal detachment/hemorrhage, cataract, intraocular inflammation, conjunctival hemorrhage, eye pain, floaters EMS None OD Unlikely, but immediate effect would be vision loss and pain d/t t ocular pressure... 

Various diseases of the natural vitreous itself, like opacification, haemorrhage, inflammation, as well as retinal detachment, may require its removal by so-called vitrectomy. 

Klinker IF, Seifert R (1997) Morphine and muscle relaxants are receptor-independent G-protein activators and cromolyn is an inhibitor of stimulated G-protein activity. Inflamm Res 46 46—50 Klinker IF, Seifert R, Datum H, Rommelspacher H (1997) Activation by beta-carbohnes of G-proteins in HL-60 membranes and the bovine retinal G-protein transducin in a receptor-independent manner. Biochem Pharmacol 53 1621-1626... 

Hermel, M., Heckelen, A., Kirchhof, B., Schrage, N.F. Inhibitory effect of ascorbic acid on human retinal pigment epithelial cell proliferation compared to cytostatic drugs-influence of histamine. Inflamm Res 50(Suppl 2), S93-S95... 

Intravitreal triamcinolone injection is safe and effective for cystoid macular edema caused by uveitis, diabetic maculopathy, and central retinal vein occlusion, and for pseudophakic cystoid macular edema. Potential risks include glaucoma, cataract, retinal detachment, and endophthalmitis. Infectious endophthalmitis is extremely rare when appropriate sterile technique is practised. Seven patients developed a clinical picture simulating endophthalmitis after intravitreal injection of triamcinolone (71). The authors believed that this effect was a toxic reaction to the injected material and explained that the differential diagnosis of infectious endophthalmitis in eyes that have been injected with triamcinolone under sterile conditions includes a sterile toxic endophthalmitis that requires careful monitoring, perhaps every 8-12 hours, in order to determine whether the inflammation is worsening or improving. Resolution occurs spontaneously, and in the absence of eye pain unnecessary intervention can be avoided. 

The drug is slowly cleared from vitreous with a half-life of approximately 55 hours in humans and is subsequently cleared from the retina. Measurable concentrations of drug are not detected in the systemic circulation following intravitreal administration. Immediate therapy of CMV retinitis with fomivirsen was more effective in delaying progression than deferred treatment in a recent clinical trial. Concurrent systemic anti-CMV therapy is recommended to protect against extraocular and contralateral retinal CMV disease. Potential side effects include iritis and vitreitis as well as increased intraocular pressure and changes in vision. An interval of at least 2-4 weeks is recommended between cidofovir administration and use of fomivirsen because of the risk of ocular inflammation. 

Because Treponema pallidum is sensitive to penicillin G, this antibiotic is the drug of choice for treatment of syphilis and syphilitic eye disease (see Table 11-1). Syphilitic eye disease can include interstitial keratitis (stromal inflammation and vascularization), episcleritis, scleritis, nongranulomatous or granulomatous iritis, iris papules (collections of dilated capillaries in the iris), chorioretinitis, papillitis, retinal vasculitis, and exudative retinal detachment. Probenecid can be added to procaine penicillin to decrease excretion of the penicillin by the kidneys, thus causing an increase in penicillin plasma levels. Penicillins are not used for the treatment of minor ocular infections such as blepharitis and conjimctivitis... 

The patient may report episodes of watering or tenderness. When reduced lOP is fc>imd by applanation tonometry, a careful examination of the woimd is necessary.This inspection is achieved by painting sodium fluorescein over the cataract incision to observe for Seidel s sign. Occasionally, the auxiliary incisions can leak, so they should also be examined. The clinician should note the appearance of the cornea, which often shows endothelial folds. After the instillation of sodium fluorescein, a waffled appearance of the cornea is generally apparent if the lOP is markedly reduced (Figure 30-3). In addition, the anterior chamber depth should be assessed as well as the presence of inflammation. The pupils should be dilated and a retinal examination should be performed to rule out serous or hemorrhagic choroidal separations or a retinal break or detachment. 

In patients with history of ocular inflammation, 1% prednisolone acetate, one drop four times a day for 3 to 7 days, can be prescribed prophylactically after Nd YAG. Rarely, a patient without history of inflammation may present with flare or mild cells in the anterior chamber or CME after capsulotomy. This also should be treated with topical steroids in the same manner. Post-YAG elevated lOP can often be prevented by treating the eye with apra-clonidine (lopidine) or other aqueous suppressant topical medication. The recommended dosage is one drop applied before the capsulotomy and one drop immediately after the procedure. Because of the potential risk of a retinal break, patients should receive dilated fundus examinations postoperatively as part of the routine follow-up within 1 to 4 weeks of capsulotomy, or sooner if symptoms develop. 

Clinical features of ARN must include (1) focal well-demarcated areas of retinal necrosis located in the retinal periphery, (2) rapid circumferential progression of necrosis, (3) evidence of occlusive vasculitis, and (4) moderate to severe anterior chamber and vitreal inflammation. Mild presentations may manifest low-grade anterior chamber inflammation with or without blurred vision, whereas severe cases may include episcleritis, scleritis, and pain on eye movement. Early clinical findings include anterior and posterior uveitis, keratic precipitates, and presence of vitreous cells. Within several days to weeks, the patient develops dramatic progressive retinal whitening in multifocal and confluent patches, vasculitis of both retinal arteries and veins, and possible optic nerve head... 

Use of systemic, periocular, or topical corticosteroids reduces intraocular inflammation, particularly vitreous opacification, but does not affect the severity of retinal necrosis. The usual dosage is 60 to 80 mg of oral prednisone for at least 1 week, followed by tapering over 2 to 6 weeks. Topical corticosteroids should be used to treat anterior segment inflammation. 

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