Secondary glaucomas represent only a small percentage of all glaucomas but these conditions are important to understand as there are critical differences in their diagnosis and management. This section will discuss several of the most common secondary glaucomas.
NEOVASCULAR GLAUCOMA (NVG)
NVG is a condition caused by new blood vessel growth on the iris and in the anterior chamber angle usually resulting from retinal ischemia and hypoxia. NVG is an unusual condition that is more common in older populations. Retinal ischemia and hypoxia associated with conditions such as central retinal vein occlusion and proliferative diabetic retinopathy are implicated in the development of neovascularization of the anterior segment. In the presence of retinal ischemia, angiogenic factors such as vascular endothelial growth factor (VEGF) stimulate the proliferation of new vessels. These angiogenic factors diffuse into the anterior chamber and promote new vessel growth, especially in tissues with prolonged exposure to the aqueous. Obstruction of the angle occurs as a result of the formation of fibrovascular membranes, which serve as scaffolding for the new blood vessels. Subsequent contracture of this membrane can lead to progressive peripheral anterior synechia and subsequent angle closure.
Due to its prolonged contact time with the aqueous, neovascularization usually appears first on the surface of the iris adjacent to the pupillary border. These vessels are fine in caliber and may have aneurism-like out-pouchings. Gonioscopic evaluation may reveal vessels in the anterior chamber angle, even in the absence of iris vessels. One emerging treatment for the management of neovascular glaucoma is the use of bevacizumab (Avastin). Avastin is a monoclonal antibody that works by attaching to and inhibiting the action of vascular endothelial growth factor (VEGF). When VEGF is bound to Avastin, it cannot stimulate the formation and growth of new blood vessels. Injected into the vitreous, this compound has been shown to produce a rapid improvement of retinal and iris neovascularization after a single injection. In addition to this emerging therapy, treatment of the underlying retinal ischemia with panretinal photocoagulation can also prevent anterior chamber neovascularization.
Neovascular glaucoma can lead to a blind, painful eye. Management includes the use of topical atropine 1% to decrease ocular congestion and topical steroids to decrease inflammation along with concurrent use of antiglaucoma medications. Still, surgery remains the main form of therapy. Surgical procedures include cyclocryotherapy, trabeculectomy and tube implant. In general, outcomes are less successful compared to primary open angle glaucoma, although used with Avastin, results may be improved.
GLAUCOMA ASSOCIATED WITH INFLAMMATION
Inflammation associated with different sectors of the eye (scleritis, uveitis, keratitis, trabeculitis) may lead to an increase in IOP substantial enough to cause glaucomatous optic atrophy. In addition, the use of corticosteroid for the treatment of these conditions may also be responsible for increased IOP (steroid responder). In both the pediatric and adult populations, the prevalence of glaucoma associated with uveitis ranges from 5% to 14%, although the etiology of the uveitis varies between these populations. In the general glaucoma population, inflammatory etiologies account for only a small percentage (< 2%) of all glaucomas. Uveitis associated with glaucoma can result from different conditions, such as anterior uveitis (e.g. idiopathic, the spondylarthropathies, juvenile rheumatoid arthritis associated uveitis), Fuch’s Heterochromic uveitis, Posner-Schlossman, Herpetic uveitis, traumatic uveitis, and lens-induced uveitis. In most cases of glaucoma associated with inflammation, the anterior chamber angle is open and the increase in IOP results from direct involvement of the trabecular meshwork as a consequence of local inflammation (e.g. secondary trabeculitis), spill-over from more generalized inflammation (e.g. panuveitis), or as a consequence of accumulation of inflammatory debris. Less commonly, local inflammation causes an increase in IOP as result of a secondary angle closure (see section on angle closure glaucoma).
The pathogenesis of steroid induced glaucoma is not fully understood. Theories include the accumulation of glycosaminoglycans in the anterior chamber angle and increased production of the TIGR/Myoc protein. The result produces increased resistance to aqueous outflow.
In addition to the treatment of the underlying cause of the uveitis, in most cases, the treatment of the ocular component of these conditions will involve both anti-inflammatory (topical corticosteroids) and anti-glaucoma medications (aqueous suppressants). Cycloplegics are used to prevent or manage posterior synechia, secondary neovascular glaucoma and choroidal effusion. Miotics are avoided because their use may exacerbate ciliary spasm, inflammation and increase the likelihood of synechia. Prostaglandins are also avoided, as this group of medications may exacerbate the inflammatory component. If the patient is found to be a steroid responder (IOP elevates over time), the initial consideration is to discontinue or change the steroid medication. If this is not feasible, given the nature of the patient’s condition, then more aggressive management of the intraocular pressure may be warranted until the steroid can be discontinued. In general, surgical (trabeculectomy and tube shunts) have less successful outcomes compared to primary open angle glaucoma.
Angle recession glaucoma is the most common form of glaucoma associated with trauma. Other forms include: glaucoma associated with hyphema (acute) or later onset (ghost cell glaucoma), trabeculitis, phacolytic glaucoma, and glaucoma associated with lens dislocation. In the acute phase, the presence of blood in the anterior chamber (hyphema) or inflammation as a result of injury (e.g. traumatic iridocyclitis) may cause an increase in intraocular pressure that mandates treatment. The long term effects of ocular trauma associated with the pathogenesis of glaucoma often occur as a result of the initial damage (angle recession) and subsequent healing of the anterior chamber angle (Figure 1). Since most patients with traumatic angle recession will not develop glaucoma (5% to 20% develops glaucoma), and elevated IOP occurs long after the antecedent trauma, it is conceivable that many cases are overlooked. Angle recession glaucoma is relatively uncommon when the recession is less than 180 degrees. Angle recession glaucoma often presents as a unilateral, or asymmetric, glaucoma without symptoms unless in an advanced stage. The patient may not recall a history of blunt ocular trauma. Diagnosis requires a 360 degree gonioscopic assessment of each eye.
Since acute increases in intraocular pressure in the setting of blunt trauma may be of short duration, observation and careful follow-up may be all that is required (assuming the presence of a healthy optic nerve prior to injury). If treatment is indicated, aqueous suppressants (e.g. beta blockers, alpha agonists) are the mainstay of treatment. Angle recession glaucoma should be treated in a similar fashion as primary open angle glaucoma (POAG). If customary glaucoma management does not produce an adequate IOP reduction, a course of cycloplegia may produce positive results. Surgical washout of the anterior chamber may be indicated in the presence of hyphema, especially if the corneal endothelium shows signs of compromise (e.g. corneal blood staining), if the hyphema does not resolve over time, or if a subsequent new hypema occurs (rebleed).
For angle recession glaucoma, in general, the results of laser and surgical procedures have less successful outcomes compared to primary open angle glaucoma.
Patients with sickle cell disease are more sensitive to increases in IOP, even of short duration (2 to 4 days). These conditions are capable of occluding the central retinal artery (due, in part, to stagnation of blood in small vessels, excessive deoxygenation of erythrocytes, erythrostasis, sickling and increased blood viscosity). It is, therefore, prudent to order a sickle prep (Sickledex) or hemoglobin electrophoresis on all patients suspected of having sickle cell disease or trait (more common among African Americans and people of Mediterranean descent) in the presence of increased IOP associated with hyphema.
PSEUDOEXFOLIATIVE GLAUCOMA (PXG)
PXG occurs throughout the world. In the United States, the prevalence ranges from 5% to 15% of all glaucoma cases. It is more common in patients > 60 y/o and uncommon in patients <40. Pseudoexfoliation syndrome is a systemic disease associated with abnormalities of the basement membrane in epithelial cells, which are found throughout the body. The accumulation of pseudoexfoliative material in the trabecular meshwork and the juxtacanicular tissue next to the Schlemm’s canal leads to obstruction of aqueous.
Pseudoexfoliation syndrome typically presents unilaterally but may become bilateral and can be an aggressive form of glaucoma that can progress rapidly. The initial signs are usually noted with slit lamp exam by observing the deposition of white, flaky material on the anterior lens capsule (Figure 3) and iris border.
Treatment of PXG is similar to that of POAG. In general, patients respond well to argon laser trabeculoplasty (ALT). Unfortunately, within five years, approximately half are back to baseline IOPs and some will have a rapid sustained increase in IOP within two years.
Pigmentary syndrome and glaucoma tend to occur at a relatively early age (20 to 45 years) with most individuals being myopic (80%), Caucasian and male. Pigment is released from the iris due to lens-iris contact, leaving radially oriented transillumination defects. The pigment circulates in the convection currents of the aqueous before adhering to the corneal endothelium forming Krukenburg’s spindle and depositing in the anterior chamber angle. PDS is generally bilateral and asymptomatic. Common signs include a Krukenburg spindle, radially oriented iris transillumination defects, and heavy pigment in the anterior chamber). In some instances, a concave iris may be present (Figure 3).
PDS can resemble postoperative conditions such as IOL-iris chafing and pseudoexfoliation; however, these are often unilateral and present with less and unevenly dispersed pigment.
Treatment should take into account the needs of the patient and the extent of glaucomatous optic neuropathy and/or visual field loss. Like pseudoexfoliative glaucoma, patients typically respond well to ALT at least initially. Laser iridotomy may alter the pressure gradient associated with a concave iris, allowing it to flatten in the anterior chamber thereby decreasing the likelihood of contact. When medical and laser intervention fail, surgical intervention is considered.
- Vatavuk Z, Bencic G, Mandic Z. Intravitreal bevacizumab for neovascular glaucoma following central retinal artery occlusion. Eur J Ophthalmol. 2007 Mar-Apr;17(2):269-71.
- Lynch SS, Cheng CM. Bevacizumab for neovascular ocular diseases. Ann Pharmacother. 2007 Apr;41(4):614-25.
- Iliev ME, Domig D, Wolf-Schnurrbursch U, Wolf S, Sarra GM. Intravitreal bevacizumab (Avastin) in the treatment of neovascular glaucoma. Am J Ophthalmol. 2006 Dec;142(6):1054-6.
- Davidorf FH, Mouser JG, Derick RJ. Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection. Retina. 2006 Mar;26(3):354-6.
- Jonas JB, Spandau UH, Schlichtenbrede F. Intravitreal bevacizumab for filtering surgery. Ophthalmic Res. 2007;39(2):121-2.
- Roberts DK, Winters JE, Castells DD, Teitelbaum BA, Alexander CC. A cross-sectional study of Krukenberg spindles and pigmented lens striae in a predominately black population: two highly associated clinical signs of anterior segment pigment dispersal. J Glaucoma. 2005 Feb;14(1):57-63.
- Papadaki TG, Zacharopoulos IP, Pasquale LR, Christen WB, Netland PA, Foster CS. Long-term Results of Ahmed Glaucoma Valve Implantation for Uveitic Glaucoma. Am J Ophthalmol. 2007 Jul;144(1):62-69.
- Kuchtey RW, Lowder CY, Smith SD. Glaucoma in patients with ocular inflammatory disease. Ophthalmol Clin North Am. 2005 Sep;18(3):421-30.
- Sung VC, Barton K. Management of inflammatory glaucomas. Curr Opin Ophthalmol. 2004 Apr;15(2):136-40.
- Walton W, Von Hagen S, Grigorian R, Zarbin M. Management of traumatic hyphema. Surv Ophthalmol. 2002 Jul-Aug;47(4):297-334.
- Schlotzer-Schrehardt U, Naumann GO. Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol. 2006 May;141(5):921-937.