The association of uveitis and glaucoma was first described by Joseph Beer.
The incidence of glaucoma associated with uveitis in both adults and children is nearly the same, i.e. 5-20%. However, the visual prognosis in children is poorer compared to adults.
When IOP is elevated for a short period and it does not induce either optic nerve or visual field damage, the term “uveitis-related ocular hypertension” may be used.
The term “uveitic glaucoma” should ideally be used when uveitis is associated with elevated IOP, glaucomatous optic nerve damage, and/or glaucomatous visual field defects.
Mutton-fat keratic precipitates (usually found in Arlt’s triangle), are present in:
iii. Sympathetic ophthalmia
iv. Phacoanaphylactic uveitis
Not all cases of uveitis are associated with high IOP. The IOP can be low, normal or high depending upon the cause.
HLA-B27 positive individuals have more severe uveitis compared to HLA-B27 negative individuals.
Certain anti-glaucoma medications such as Brimonidine can cause uveitis. Whether prostaglandin analogues can also lead to such a situation is not known.
Dynamic gonioscopy is a useful test to perform in order to differentiate between appositional versus synechial closure. The latter being commonly seen in glaucoma associated with uveitis.
Posterior segment findings in uveitis include= vascular sheathing, perivascular exudates, cystoid macular edema, retinitis, choroidal infiltrates, retinal detachment, pigmented or atrophic scars and pars plana exudates (snowbanking) and glaucomatous optic nerve head changes.
T-cells lay a major role in the pathogenesis of uveitis. They are the most abundant cell type in uvea, retina, aqueous and vitreous in patients with uveitis.
In normal eyes, the protein content in aqueous humor is approximately 1/100th of that in serum. However, during inflammation the protein content of the aqueous humor increases. It is a non-specific transudation due to increased permeability of the blood-aqueous-barrier. The probable sites of protein leakage include: disrupted ciliary epithelium and proliferating blood vessels.
Fluorescein angiography of iris reveals hypoperfusion and microneovascular changes suggesting another site from where protein leakage could occur.
Prostaglandins have been found to be increased in uveitis but they are not presumed to play a role in uveitis-induced ocular hypertension.
Inflammatory mediators (Cytokines) and toxic agents (Oxygen Free Radicals) also play a role. Cytokines are soluble polypeptides which play a critical role in the immune response by regulating leucocyte interactions. They are secreted principally by monocytes/macrophages and lymphocytes, although any cell which participates in the immune response may secrete them (e.g. neutrophils, endothelial cells and fibroblasts). Cytokines (IL- 1, IL-2 and Tumor Necrosis Factor [TNF]) may influence IOP by increasing the inflammation by stimulating neovascularization and by having a direct effect on aqueous humor dynamics. Tissue Growth Factor (TGFβ-2) a potent immunosuppressive normally present in the eye is decreased or absent in the aqueous and vitreous of eyes with various inflammatory disorders.
Oxygen Free Radicals are released by macrophages and Polymorphonuclear Neutrophils (PMNs). PMNs and macrophages undergo a “respiratory burst” which is characterized by increased consumption of oxygen, increased utilization of glucose via the Hexose MonoPhosphate Shunt pathway and release of oxygen metabolites.
It has been proposed that the superoxide radical itself is poorly reactive in aqueous solution and the tissue damaging effects are more from reactive secondary products e.g. Hydrogen Peroxide, Hypochlorous Acid and Hydroxyl radicals.
Damage to the trabecular meshwork or angle structures by OFRs may cause a rise in IOP.
Posterior synechiae occur more commonly in granulomatous than non-granulomatous uveitis.
Peripheral anterior synechiae (PAS) may form secondary to inflammation, neovascularization or iris bombe.
Pseudo-exfoliative glaucoma may induce more inflammation than primary open angle glaucoma (POAG) because of the very labile blood aqueous barrier balance.
Secondary open angle glaucoma associated with uveitis due to mechanical blockage or dysfunction of outflow pathway, results in decreased outflow facility. The level of IOP will depend upon the rate of aqueous humor production by the ciliary body.
Trabeculitis may also contribute to a rise in IOP. This is characterized by inflammatory precipitates on the trabecular meshwork. Since trabeculitis is usually not associated with concomitant inflammation of the secretory ciliary epithelium, aqueous production is normal. The elevated IOP is purely as a result of reduced aqueous outflow.
Swelling or dysfunction of the trabecular beams or endothelial cells can cause a reduction in diameter of trabecular pores.
b. IOP usually rises 2 or more weeks after initiating steroid therapy. (But may occur anytime)
c. Steroids can be instilled in the opposite eye to look for steroid responsiveness.
d. Steroids increase IOP by reducing aqueous outflow. Many theories have been proposed to explain this phenomenon, including: accumulation of glycosaminoglycans in the trabecular meshwork (by inhibiting their catabolism; inhibition of phagocytosis of foreign material by trabecular endothelial cells; inhibition of synthesis of prostaglandins (PGE2 and PGF2, which increase the outflow facility).
· Taper steroids
· Change to lower concentration or a drug with lesser tendency to elevate IOP e.g. Medrysone or fluoromethalone.
· Rimexolone has maximal anti-inflammatory effects and minimal effects on IOP elevation. (1% suspension as effective as 1% Prednisolone in management of uveitis. Prednisolone 1% is 1.7-8 times more likely to produce IOP elevation). In mild cases the steroid can be replaced by NSAIDs. While in severe cases it can be replaced with immunosuppressives. In depot steroid injections (Triamcinolone), the IOP may remain elevated for 18 months or more. This often requires surgical removal of depot-steroid or filtration surgery.
Management of uveitic glaucomas:
(A) Medical therapy:
Agents which reduce IOP e.g. beta-blockers.
Adrenergic agonists= epinephrine, dipivefrine, apraclonidine.
Carbonic anhydrase inhibitors.
Miotics should be avoided as they potentiate posterior synechiae and pupillary membrane formation; cause discomfort by aggravating ciliary spasm and increase inflammation by increasing breakdown of blood-aqueous barrier and accelerating release of enzymes from PMNs.
(B) Surgical therapy:
i. Uveitis is associated with cellular changes in conjunctiva including increased numbers of fibroblasts, lymphocytes and macrophages, which are important causes of filtering surgery failure. Therefore, the eye should be quite for 3 months prior to surgery and operated under steroid cover. In certain patients topical prednisolone 1% eyedrops hourly and Oral prednisolone 40mg per day can be instituted 1 week prior to surgery. At the time of surgery a depot of corticosteroid should be injected sub-conjunctivally far from the bleb.
ii. Surgical iridectomy can be done in those eyes, where laser PI is not successful. However, iridectomies are only effective in the eyes which have PAS involving <75% of the angle. It has fewer propensities for closure, but induces more inflammation compared to laser procedures.
iii. In case the iridotomy is not successful, then filtering surgeries or destruction of the ciliary body can be done.
(C) Laser procedures:
In case of angle closure, laser iridotomy can be done. Combined Argon and Nd:YAG lasers are more effective in thicker irides. To prevent inflammation, topical steroids can be instilled every 5 minutes for 30-60 minutes and then every 6 hours for 1-2 weeks.