Secondary glaucomas span a wide array of conditions for which there is an identifiable cause for elevation in intraocular pressure (IOP). These secondary glaucomas are often more aggressive and require appropriate diagnosis to guide treatment, which can differ greatly in the variety of useful options and intensity of recommended intervention.
Knowing key findings and appropriate management steps for these various conditions is critical for preserving optic nerve health and patient vision. This article will review keys to proper diagnosis and review some of the most commonly encountered secondary glaucomas.
What is secondary glaucoma?
Once high IOP and/or glaucomatous nerve damage has been identified, there are several factors that can help land on the appropriate cause for secondary glaucoma.
Patient history plays an essential role in diagnosis, with important details including:
- Pertinent systemic health disorders (such as diabetes or cardiovascular abnormalities)
- Systemic or topical medications (steroids, topiramate, anticholinergics)
- Ocular surgical history
- History of ocular trauma
These details may rule out differential diagnoses or help to clue the provider into certain causes to look carefully for.
How to identify secondary glaucoma during an eye exam
Once a comprehensive history has been established, a thorough slit lamp examination should be performed. Findings such as corneal endothelial pigment or pseudoexfoliative material on the anterior lens capsule may be present to guide or confirm the diagnosis.
Gonioscopy is essential for diagnosis in most secondary glaucoma, as direct visualization of the angle will unveil any depositions or irregularities that are causing IOP elevation. Even in the case of suspected primary open-angle glaucoma, gonioscopy is required to rule out other acquired causes of impaired aqueous outflow.
Once the angle has been visualized, dilated fundus examination is essential for detailed optic nerve evaluation and for any final hints, such as peripheral neovascularization or evidence of ocular trauma, that may explain elevated IOP.
Diagnostic and management considerations for secondary glaucomas
Pseudoexfoliative glaucoma
Pseudoexfoliation (PXF) is primarily a condition seen in older, Caucasian patients of northern European and Eastern Mediterranean descent. Patients with pseudoexfoliation glaucoma will present with the classic white fibrillary material on the anterior lens capsule, often in a bullseye pattern due to pupillary fluctuation leading to sloughing of this material in the mid-periphery.
While this finding is pathognomonic for PXF glaucoma, pseudophakic patients will not have this deposition, and as such, other key findings can help guide diagnosis. Gonioscopy will exhibit the classic Sampaolesi line, most evident in the inferior aspect of the angle. This line indicates a buildup of PXF material that is inhibiting aqueous outflow. These patients may also exhibit a moth-eaten atrophic appearance to the pupillary margin due to iris-lens rubbing.
PXF leads to brittle zonules which may lead to dislocation of the lens before, during, or after cataract surgery. PXF may be bilateral, but the presentation is often asymmetric, and as such should be considered in patients who fit the typical demographic with very asymmetric damage or IOP elevation.
Figure 1 demonstrates a dislocated IOL in a patient with pseudoexfoliative glaucoma. Diagnosing PXF in pseudophakic patients may be more difficult than in phakic patients who often clearly exhibit the classic white fibrillary material on the anterior lens capsule. Findings such as spontaneous lens dislocation may help in properly diagnosing PXF.
Figure 1: Courtesy of Chris Kruthoff, OD, FAAO.
Pseudoexfoliation can be quite aggressive in nature, both at presentation and even after treatment has been initiated. As such, these patients should be watched closely, and earlier initiation of treatment in the suspect phase may be warranted.
These patients may be excellent candidates for trabeculotomy procedures, which help to unroof the trabecular meshwork to eliminate PXF material in the treated areas from impeding aqueous outflow.2
Pigmentary glaucoma
Pigmentary glaucoma is the result of the liberation of iris pigment due to contact between a posteriorly bowed iris and lens zonules. This pigment circulates into the anterior chamber and ultimately deposits into the angle, creating an obstruction of aqueous outflow in a similar fashion to PXF.
Pigmentary glaucoma often impacts patients of a younger age than other glaucomas, with the classic patient being male with moderate myopia.3 Hallmark findings include Krukenberg’s spindle (pigment deposition on the corneal endothelium), radial iris transillumination defects, and dense pigmentation of the posterior trabecular meshwork on gonioscopy.
These findings may be less evident as the patient ages, where changes to lens thickness may alleviate the iridozonular contact, leading to a “burnout” phase, and causing clearance of the built-up meshwork pigment starting in the inferior angle.4
YAG peripheral iridotomy has been considered as a treatment option for pigmentary glaucoma, with this procedure being used to balance pressure between the anterior and posterior chambers and thus less posterior force on the iris.5,6 The utility of this procedure is controversial, with trials yielding conflicting results.7,8
Selective laser trabeculoplasty (SLT) may be utilized for IOP control, but energy must be titrated to lower levels to avoid an excessive inflammatory response. Some studies suggest the efficacy of SLT in pigmentary glaucoma is lower than that seen in primary open-angle glaucoma.9,10
Neovascular glaucoma (NVG)
Neovascularization results from ischemia of the eye, typically the posterior segment, resulting in the release of vascular endothelial growth factor (VEGF) and ultimately the proliferation of a fibrovascular membrane.11
As this fibrovascular net proliferates, it may encroach the trabecular meshwork and impede aqueous outflow or lead to the formation of peripheral anterior synechiae, leading to acute and severe IOP spikes.11
Iris neovascularization typically emanates from the pupillary margin toward the angle. Early cases will be sectoral and may be discrete; more advanced cases may present with florid proliferation.
Eventually, neovascularization may reach and occlude the trabecular meshwork, obstructing aqueous outflow via fibrovascular closure or formation of peripheral anterior synechiae. As such, it is important to utilize gonioscopy in patients with unexplained high IOP to evaluate for neovascularization of the angle.
Figure 2 illustrates florid iris neovascularization secondary to ocular ischemic syndrome. The presence of iris neovascularization requires urgent consultation with a retina specialist for anti-VEGF therapy. IOP management should be aggressive and often requires surgery for adequate control.
Figure 2: Courtesy of Chris Kruthoff, OD, FAAO.
While lowering IOP is important, referral for treatment should first go to a retinal specialist, where anti-VEGF therapy should be promptly delivered to halt proliferation. Anti-VEGF therapy is useful in limiting further neovascularization and increasing the odds of surgical glaucoma success.12,13
NVG is often recalcitrant to topical therapies due to the substantial aqueous outflow obstruction, and surgical intervention with a glaucoma drainage device, therefore, is regularly implemented. Early referral for surgical consult is warranted in cases to prevent prolonged periods of IOP elevation.
It is important to note that these eyes accompany significant systemic morbidity. Common causes of NVG include proliferative diabetic retinopathy, central retinal vein occlusion, and ocular ischemic syndrome (OIS).
For patients with uncontrolled diabetes, prompt referral back to their appropriate provider is important for improved blood glucose control. Patients with central retinal vein occlusion should undergo a thorough cardiovascular workup to evaluate for factors that may have contributed to thrombus formation. In cases of OIS, cardiovascular evaluation with the inclusion of carotid ultrasound is essential, as these patients have a particularly high mortality rate.14
Traumatic glaucoma
Patients who experience trauma to the eye may be at risk of glaucoma development both in the acute phase, where hyphema may occlude normal outflow channels, and the chronic phase, where scarring of trabecular meshwork or Schlemm’s canal can limit or outright block drainage.
As seen in Figure 3, hyphema after ocular trauma may lead to marked IOP elevation. These patients must be followed closely and may need surgical washout if IOP does not respond to medications.
Figure 3: Courtesy of Chris Kruthoff, OD, FAAO.
For patients with high IOP due to hyphema, topical aqueous suppressants should be used until blood clears and IOP normalizes. Oral carbonic anhydrase inhibitors such as acetazolamide may also be effective but should be avoided in patients with sickle cell anemia due to the risk of acidosis that can lead to red blood cell sickling.
Anterior chamber washout and glaucoma drainage device may be indicated in patients with marked and prolonged IOP elevation (>60mmHg for 2 days or >25mmHg for 5 days with total hyphema) with or at lower levels in patients with sickle cell anemia (>25mmHg for 24 hours on maximum medical therapy) due to the higher susceptibility to glaucoma.15
While gonioscopy is typically withheld in the immediate aftermath of trauma, it is imperative once active inflammation and hyphema clear to evaluate for any evidence of angle recession, as this may increase the risk of glaucoma development.
Angle recession presents as a widened area of ciliary body indicating partial separation of the longitudinal and circular fibers of the ciliary body. These areas indicate trauma affecting the angle directly and are concerning for damage and scarring to the trabecular meshwork and Schlemm’s canal.
Patients with over 180° of angle recession are especially concerning for glaucomatous progression.16 These patients should be educated about their lifelong risk of glaucoma, as some cases may not present for years.
Angle recession glaucoma cases can vary based on the extent of damage, with larger areas of recession being more difficult to treat due to the extent of outflow damage. In mild cases, topical hypotensives may prove to be effective.
SLT has traditionally been thought to be ineffective in patients with angle recession, but newer studies indicate some patients may show short-term benefits.17 In more advanced cases, patients may need surgery to bypass the non-functioning outflow channels with trabeculectomy or drainage devices.
Uveitic glaucoma
Uveitis may lead to glaucoma via several different mechanisms. While acute anterior uveitis will typically present with low IOP due to decreased aqueous production from ciliary block, some conditions—most notably herpes simplex and herpes zoster—may commonly present with elevated IOP secondary to trabeculitis.
Other conditions, such as glaucomatocyclitic crisis (Posner-Schlossman Syndrome) and Fuchs’ heterochromic iridocyclitis (FHI), may also present with dramatically elevated IOP in the acute inflammatory phase. In chronic or uncontrolled cases of anterior uveitis, peripheral anterior synechiae may form causing blockage of aqueous outflow.
Acute anterior uveitis, as seen in Figure 4, should be managed aggressively with steroids to avoid progression to peripheral anterior synechiae and chronic aqueous outflow obstruction. Conversely, high frequency and chronic steroid use may lead to a steroid response—IOP should be monitored regularly in these patients.
Figure 4: Courtesy of Chris Kruthoff, OD, FAAO.
Management of uveitic glaucoma is challenging, as each case and etiology requires different approaches. Patients with recurrent or aggressive uveitis should be evaluated for a causative factor, which should be addressed to prevent future flares. Topical steroid use is critical to prevent inflammatory sequelae such as synechiae, though it should be noted that FHI is typically unresponsive to topical steroids.
Patients who are on any steroid therapy should be monitored closely for steroid response. While cessation of steroids will allow for IOP to return to normal, this may not be an option if inflammation remains uncontrolled.
The use of aqueous suppressants is necessary in these cases to help moderate IOP. Prostaglandin analogs, typically a first-line topical option, should be avoided in cases of active uveitis as this may prolong or exacerbate the condition.
For patients who have extensive peripheral anterior synechiae or require chronic steroids in the presence of an uncontrolled steroid response, more invasive surgical measures such as glaucoma drainage devices may be necessary to keep IOP in the normal range.
It is best to have inflammation as quiet as possible before these procedures, as the presence of active inflammation may induce scarring and ultimately failure of these procedures.18
Conclusion
Secondary glaucomas present unique management challenges. Given the aggressive nature of these conditions, accurate diagnosis as to the inciting cause is essential.
It is important to obtain thorough systemic and ocular history, perform an astute slit lamp examination, and utilize ancillary testing such as gonioscopy to come to the correct diagnosis.
Implementing aggressive topical treatment can be helpful in lowering IOP, but many cases may require surgical intervention for long-term IOP control.
Be prepared to make these referrals promptly and appropriately, as they may be sight-saving for your patients.
