Secondary glaucoma refers to a group of glaucomas caused by certain ocular or systemic diseases that interfere with or disrupt the normal circulation of aqueous humor, resulting in increased intraocular pressure (IOP) due to obstruction of aqueous outflow pathways. Its etiology is relatively clear. Secondary glaucoma often involves only one eye and generally lacks a familial predisposition. Based on whether the anterior chamber angle remains open or becomes closed under elevated IOP, secondary glaucoma can be classified into open-angle and angle-closure types.
Compared to primary glaucoma, secondary glaucoma includes not only the harmful factor of elevated IOP but also the presence of more severe primary pathological conditions, which often cause varying levels of damage to ocular tissues. This makes the diagnosis and treatment of secondary glaucoma more complex, and the prognosis tends to be worse.
Glaucomatocyclitic Crisis
Glaucomatocyclitic crisis, also known as Posner-Schlossman syndrome, predominantly occurs in middle-aged men. Typical cases exhibit episodic IOP elevation, which can exceed 50 mmHg. Alongside or before/after the IOP elevation, signs such as keratic precipitates resembling mutton-fat appear. The anterior chamber is deep, the angle remains open, the aqueous humor shows no obvious turbidity, and posterior synechiae of the pupil are absent. Spontaneous resolution typically occurs within a few days. Compared to primary open-angle glaucoma (POAG), the prognosis is better, but recurrences are common. The condition’s episodes can be shortened by the use of topical timolol, corticosteroids, and oral acetazolamide.
Steroid-Induced Glaucoma
Prolonged use of corticosteroids, whether topically or systemically, can lead to elevated IOP, resulting in steroid-induced glaucoma. Individual sensitivity to corticosteroids varies, and the degree of IOP elevation is also influenced by the type, concentration, frequency, and duration of corticosteroid use. The clinical presentation of steroid-induced glaucoma is similar to POAG, and a history of corticosteroid use aids in differential diagnosis. In most cases, IOP gradually normalizes after discontinuation of corticosteroids. In rare cases where IOP remains persistently elevated after drug withdrawal, treatment follows the principles for managing open-angle glaucoma.
POAG with an insidious onset may show significant IOP elevation following the use of corticosteroids. Individuals suspected of glaucoma or those with a family history of glaucoma are particularly advised against long-term administration of corticosteroids. For patients requiring long-term corticosteroid therapy for clinical reasons, regular monitoring of IOP is necessary.
Secondary Glaucoma Caused by Ocular Trauma
Acute IOP elevation shortly after blunt ocular trauma is often associated with significant hyphema or direct damage to the trabecular meshwork. The elevated IOP may be caused by red blood cell accumulation in the trabecular meshwork, pupillary block from blood clots, or inflammatory edema of the damaged trabecular meshwork impeding aqueous outflow. Management includes the use of topical corticosteroids to reduce inflammation, timolol, and oral acetazolamide or intravenous mannitol if necessary to control IOP. IOP usually normalizes as the hyphema resolves. However, in cases of excessive IOP elevation, inadequate control, or the presence of corneal blood staining, anterior chamber paracentesis to evacuate the hyphema can be performed.
Intraocular hemorrhage, particularly vitreous hemorrhage, can occasionally lead to hemolytic glaucoma or ghost cell glaucoma. The pathogenesis in these cases involves either macrophages containing hemoglobin or degenerated red blood cells obstructing the trabecular meshwork, thereby reducing aqueous outflow and causing elevated IOP. IOP is likely to normalize as the intraocular blood clears. Medication is usually the first-line treatment for controlling IOP in such cases. For rare instances where IOP remains uncontrolled, anterior chamber irrigation can be considered.
Angle-recession glaucoma may occur months or years after blunt ocular trauma. Its clinical presentation resembles POAG. A history of previous blunt ocular trauma, hyphema, and signs of abnormal angle recession observed on gonioscopy assist in diagnosis. Treatment principles are the same as for POAG.
Cases involving ocular trauma, corneal perforation, adherent leukomas, or anterior segment surgery that lead to prolonged non-formation of the anterior chamber may result in permanent synechiae of the peripheral iris and trabecular meshwork. This leads to closure of the anterior chamber angle and causes secondary angle-closure glaucoma.
Lens-Induced Glaucoma
During the progression of cataracts, lens swelling can occur, pushing the iris forward, leading to a shallow anterior chamber and angle closure. This situation may result in a sudden increase in IOP, resembling acute angle-closure glaucoma. The treatment typically involves lens extraction. If extensive synechiae have already formed in the angle, combined cataract and glaucoma surgery can be considered.
In the hypermature stage of cataracts, liquefaction of the lens cortex may allow proteins to leak into the anterior chamber, where they are phagocytized by macrophages. Macrophages containing lens proteins, along with large molecular-weight lens proteins, can obstruct the trabecular meshwork, reducing aqueous outflow and increasing IOP. Clinical manifestations include ocular pain and pressure, aqueous humor turbidity, and lens nucleus sinking. Treatment involves achieving medical control of IOP first, followed by cataract extraction. Preoperative use of topical corticosteroids can help alleviate lens-induced phacogenic uveitis.
Traumatic or spontaneous lens dislocation, as seen in conditions such as Marfan syndrome, can also cause elevated IOP. A dislocated lens may move forward and become stuck in the pupillary area, dislocate into the anterior chamber, or move posteriorly into the vitreous cavity. For anteriorly dislocated lenses, lens extraction may be necessary. If the lens dislocates into the vitreous cavity and causes elevated IOP, medical therapy to control IOP may be attempted first. Additionally, lens subluxation or dislocation may increase the lens's anteroposterior diameter or, due to zonular rupture or vitreous displacement, induce pupillary block. This leads to a shallow anterior chamber, angle closure, and elevated IOP.
Spherophakia, a congenital condition, presents as a spherical-shaped lens that can result in pupillary block and angle closure. Cycloplegic agents may reduce the lens thickness and shift it posteriorly, relieving pupillary block, whereas miotic agents may exacerbate the condition. Micro-spherophakia can have a familial history, occur sporadically, or coexist with syndromes like Weill-Marchesani syndrome or Marfan syndrome.
Secondary Glaucoma Caused by Iridocyclitis
Iridocyclitis can lead to ring-shaped posterior synechiae (pupillary block), preventing aqueous humor from flowing from the posterior chamber into the anterior chamber. This results in increased posterior chamber pressure, pushing the iris forward, causing anterior bowing and angle closure, which leads to secondary glaucoma. During acute iridocyclitis, the maintenance of pupil dilation can prevent the formation of posterior synechiae. Once pupillary block occurs, with iris bowing, laser iridotomy should be performed promptly to prevent peripheral anterior synechiae and permanent damage to the trabecular meshwork. Additionally, inflammatory byproducts can obstruct the trabecular meshwork, or inflammation affecting the trabecular meshwork itself, combined with peripheral anterior synechiae formation, can block aqueous outflow, causing secondary glaucoma.
Treatment generally involves the use of aqueous humor suppressants to reduce IOP. Since miotic agents may worsen iridocyclitis, their use is not recommended. If irreversible synechiae develop in the anterior chamber angle and medical therapy fails to control IOP, filtering surgery may be performed after inflammation is adequately controlled.
Neovascular Glaucoma
Neovascular glaucoma (NVG) is a refractory secondary glaucoma that develops as a result of widespread retinal ischemia, such as in retinal vein occlusion or diabetic retinopathy. A key clinical feature is the presence of neovascularization on the iris (rubeosis iridis) in eyes with underlying retinal vascular disease. In early stages, the fibrovascular membrane blocks aqueous outflow pathways, while in later stages, contraction of the fibrovascular membrane leads to angle closure, significantly increasing IOP and causing severe pain.
Management of this condition is challenging. While topical beta-blockers and cycloplegics may alleviate symptoms, disease progression often remains difficult to control. Conventional filtration surgeries frequently fail. Preoperative panretinal photocoagulation (PRP) or cryotherapy can induce regression of neovascularization and, along with intraoperative and postoperative use of antimetabolites, may improve surgical success rates. Recently, aqueous shunt devices or valve implants have also been utilized for NVG management.
If these methods fail, procedures targeting ciliary body destruction to reduce aqueous production, such as cyclodestructive surgeries, can help lower IOP and relieve symptoms. Retinal hypoxia and capillary nonperfusion are the underlying causes of iris neovascularization; therefore, early panretinal photocoagulation is recommended in cases of retinal ischemia to prevent neovascularization. Intravitreal injection of anti-VEGF agents, either alone or in combination with surgery, has proven effective in reducing neovascular activity and permeability, promoting the regression of iris and angle neovascularization, and better controlling IOP.
Ciliary Block Glaucoma
Ciliary block glaucoma, also known as malignant glaucoma, is characterized by misdirection of aqueous humor and is often observed after intraocular surgeries. The primary mechanism involves adhesion between the lens or vitreous and the edematous ciliary processes, preventing aqueous humor in the posterior chamber from entering the anterior chamber. Instead, the aqueous humor flows backward and accumulates within or behind the vitreous cavity. This leads to an increase in vitreous volume, causing anterior displacement of the lens-iris diaphragm, which results in a uniformly shallow anterior chamber and angle closure.
Ciliary block glaucoma most commonly occurs in the early postoperative period following glaucoma surgery, particularly after discontinuation of cycloplegic agents or the use of miotic medications. If an unformed anterior chamber is accompanied by elevated IOP, congestion, and pain after glaucoma surgery, the possibility of this condition should be considered. Management involves the use of 1%–2% atropine to achieve full ciliary muscle paralysis and induce posterior displacement of the anteriorly shifted lens-iris diaphragm. Intravenous administration of hyperosmotic agents, such as mannitol, reduces vitreous volume, while acetazolamide is used to lower IOP, and systemic and topical corticosteroids help control inflammatory responses.
Some patients may respond to the above medical treatments, but long-term use of atropine is often necessary to prevent recurrence. For those unresponsive to medical therapy, drainage of accumulated vitreous fluid and reconstruction of the anterior chamber may be required. Lens extraction and anterior vitrectomy can also be performed if necessary.
Iridocorneal Endothelial Syndrome
Iridocorneal endothelial syndrome (ICE) is potentially related to herpes virus infections and is more commonly observed in middle-aged women, almost exclusively affecting one eye. It encompasses three related conditions: progressive iris atrophy, Cogan-Reese syndrome (iris nevus syndrome), and Chandler syndrome. These three disorders share corneal endothelial abnormalities and varying degrees of endothelialization of the anterior chamber angle and the iris surface. Secondary glaucoma is a significant feature of ICE.
Progressive iris atrophy manifests as corectopia (displacement of the pupil), atrophy of the iris stroma and pigment epithelium, and the formation of holes in the iris. Cogan-Reese syndrome is characterized by nodular or diffuse pigmentation on the iris surface, while Chandler syndrome features impaired corneal endothelial function and pronounced corneal edema. Endothelialization of the anterior chamber angle and peripheral anterior synechiae are responsible for the IOP elevation and secondary glaucoma associated with this condition.
Currently, no specific treatment exists for ICE. Management of secondary glaucoma focuses on controlling IOP with aqueous humor suppressants in the early stages. If medical therapy is ineffective, filtration surgery may be attempted.
Pigmentary Glaucoma
Pigmentary glaucoma results from the deposition of dispersed pigment within the trabecular meshwork, causing obstruction of aqueous outflow and an increase in IOP. This condition is more prevalent in males aged 25–40 and has a familial association, being inherited in an autosomal dominant pattern with its gene localized to chromosome 7. Patients are frequently myopic and exhibit deep anterior chambers and wide angles.
A key characteristic is the concave configuration of the mid-peripheral iris. During pupillary movement, friction occurs between the iris and the underlying zonules, causing pigment granules to detach into the anterior chamber. These granules can deposit on the posterior corneal surface and the trabecular meshwork. The characteristic pigmentary keratic precipitates (KP) are vertically distributed in a spindle shape (Krukenberg spindle). Additionally, pigment dispersion can create radial transillumination defects in the iris, though such defects are less commonly observed in Chinese patients. Ultrasound biomicroscopy (UBM) may reveal contact between the iris and the zonules.
Medical management typically involves the use of low-concentration pilocarpine eye drops to constrict the pupil, reducing friction between the iris and the zonules, limiting pigment dispersion, and enhancing aqueous outflow. Pilocarpine also facilitates the clearance of pigment granules within the trabecular meshwork, thereby lowering IOP. Aqueous humor suppressants can reduce IOP but may inhibit pigment clearance. For patients whose IOP cannot be controlled with medical management, filtration surgery may be considered.