Ghost cell glaucoma is a secondary open-angle glaucoma in which degenerated red blood cells (ghost cells) after vitreous hemorrhage obstruct the trabecular meshwork, increasing resistance to aqueous outflow and causing elevated intraocular pressure 1). It was first reported by Campbell et al. in 1976.
Ghost cells are hollow spheroids that result from red blood cells retained in the vitreous for several weeks or more, having lost most of their cellular contents (hemoglobin) and retaining only denatured hemoglobin. Compared to normal red blood cells, their deformability is markedly reduced, making it difficult for them to pass through the trabecular meshwork.
There are several types of glaucoma associated with intraocular hemorrhage besides ghost cell glaucoma 1).
| Type | Mechanism | Onset Timing |
|---|---|---|
| Hyphema | TM obstruction by red blood cells | Immediately after injury |
| Hemolytic | TM obstruction by macrophages | Days to weeks |
| Ghost cell | TM obstruction by degenerated red blood cells | 1 to 3 months |
Hemolytic glaucoma and ghost cell glaucoma may have similar clinical presentations1). Microscopic examination of anterior chamber aspirate is useful for differentiation.
In addition to decreased vision due to vitreous hemorrhage, symptoms associated with elevated intraocular pressure appear some time after the hemorrhage. The degree of intraocular pressure elevation varies depending on the amount of vitreous hemorrhage and the migration of ghost cells into the anterior chamber.
The main subjective symptoms are as follows:
Intraocular pressure rises markedly, sometimes reaching 60–70 mmHg. Characteristically, the pain is milder than expected from such severe pressure elevation.
Anterior chamber findings: Small, khaki-colored (earthy brown) spherical cells circulate in the anterior chamber1)2). When ghost cells are abundant, they form a pseudohypopyon. If fresh red blood cells and ghost cells coexist, the heavier fresh red blood cells settle inferiorly and the lighter khaki-colored ghost cells layer superiorly, creating a “candy stripe” appearance.
Gonioscopic findings: The angle is open, and ghost cells may be deposited in a layered fashion on the lower trabecular meshwork1). No angle closure is observed.
Vitreous findings: The vitreous shows signs of old hemorrhage, with khaki-colored red blood cells and extracellular pigment clumps from degenerated hemoglobin.
Corneal findings: Persistent high intraocular pressure can cause corneal edema. When severe hyphema is combined with high intraocular pressure, corneal blood staining may occur.
The direct cause of ghost cell glaucoma is vitreous hemorrhage1). Causes of vitreous hemorrhage include the following:
Two conditions are necessary for the development of ghost cell glaucoma.
Ghost cell glaucoma rarely develops from hyphema alone.
Risk factors for post-traumatic glaucoma include older age, initial visual acuity less than 0.1, iris injury, lens injury, hyphema, and angle recession.
The diagnosis of ghost cell glaucoma is based on clinical findings. It is diagnosed by integrating the following elements.
Definitive diagnosis can be made by microscopic examination of anterior chamber aspirate. Phase-contrast microscopy reveals spherical red blood cells with degenerated hemoglobin residues (Heinz bodies) inside the cell membrane. Heinz bodies are also observed with H&E staining.
When intraocular pressure rises after vitreous hemorrhage, neovascular glaucoma must always be ruled out 1). Particular caution is needed in patients with a history of diabetes or retinal vascular disease.
Hemolytic Glaucoma
Mechanism: Macrophages containing hemoglobin obstruct the trabecular meshwork
Anterior chamber findings: Reddish cells
TM discoloration: Reddish-brown pigmentation 1)
Onset: Days to weeks after hemorrhage
Features: Similar clinical presentation to ghost cell glaucoma 1)
Hemosiderotic Glaucoma
Mechanism: Chronic damage to the trabecular meshwork due to iron deposition
Anterior chamber findings: No ghost cells observed
TM discoloration: Only slight discoloration
Onset: Several years after the causative injury
Features: Extremely rare chronic glaucoma
In hemolytic glaucoma, macrophages containing hemoglobin and red blood cell fragments obstruct the trabecular meshwork, and the aqueous humor appears reddish. In contrast, in ghost cell glaucoma, degenerated, hollow, khaki-colored ghost cells obstruct the trabecular meshwork. Microscopic examination of anterior chamber aspirate can differentiate the two. However, clinical presentations may be similar 1).
Aqueous humor suppressants are first-line treatment 2). Beta-blockers, carbonic anhydrase inhibitors, and alpha-2 agonists are used alone or in combination. In the acute phase with extremely high intraocular pressure, oral carbonic anhydrase inhibitors or intravenous mannitol may be added.
If intraocular pressure cannot be controlled with medication, surgical treatment is considered. Surgical removal of ghost cells is desirable to eliminate the cause of elevated intraocular pressure.
Anterior chamber washout: Ghost cells are washed out via anterior chamber paracentesis. This is a relatively simple and safe procedure that can be repeated. However, ghost cells from the vitreous may reaccumulate after washout.
Pars plana vitrectomy (PPV): Performed when anterior chamber washout is insufficient. This is a definitive treatment that removes the source of ghost cells in the vitreous cavity.
Filtering surgery: For refractory glaucoma caused by chronic trabecular meshwork obstruction by ghost cells, trabeculectomy or glaucoma drainage device implantation may be indicated. However, prior trauma or surgery often leads to conjunctival scarring, making filtering surgery difficult. In refractory cases, cyclodestructive procedures or glaucoma implant surgery may also be considered.
Ghost cell glaucoma is usually a transient condition and resolves once the vitreous hemorrhage clears. When the supply of ghost cells in the vitreous cavity is exhausted, reaccumulation in the anterior chamber stops. However, complete resolution may take weeks to months. Persistent poor intraocular pressure control can lead to optic nerve damage, so early appropriate treatment is important.
In most cases, ghost cell glaucoma is transient and resolves once the vitreous hemorrhage clears. Intraocular pressure is controlled with aqueous suppressant medications while monitoring, and in refractory cases, ghost cells are removed via anterior chamber washout or vitrectomy. Once the supply of ghost cells in the vitreous cavity is exhausted, reaccumulation stops.
Three to ten days after vitreous hemorrhage, the clot undergoes fibrinolysis, and red blood cells diffuse throughout the vitreous cavity. Red blood cells that remain in the vitreous for several weeks or more undergo the following changes:
Ghost cells formed in this way have the following characteristics compared to normal red blood cells.
Because ghost cells have lost their deformability, they cannot pass through the pores of the trabecular meshwork 1). When a large number of ghost cells flow into the anterior chamber, they accumulate in the trabecular meshwork, causing a sharp increase in aqueous outflow resistance.
The route of entry into the anterior chamber is through the anterior vitreous face (anterior hyaloid membrane) damaged by surgery, trauma, or spontaneous rupture 1). Without this route, ghost cells cannot reach the anterior chamber and glaucoma does not develop.
The degree of intraocular pressure elevation depends on the amount of vitreous hemorrhage, the extent of ghost cell degeneration, and the amount of migration into the anterior chamber. It persists for weeks to months, and in severe cases presents with symptoms of high intraocular pressure such as corneal edema, eye pain, and nausea.
In traumatic hyphema, rebleeding may occur 3–7 days after injury (frequency 5–10%) 2). Rebleeding is often more severe and copious than the initial bleed. Massive hyphema can present as an “8 ball hyphema,” where the entire anterior chamber appears dark brown.
Ghost cell glaucoma rarely develops from hyphema alone. For ghost cells to form, red blood cells must be trapped in the vitreous for several weeks, and the anterior vitreous face must be disrupted to create communication between the vitreous and anterior chamber. Intraocular pressure elevation from hyphema alone is due to direct obstruction of the trabecular meshwork by red blood cells themselves, which is a different mechanism from ghost cell glaucoma.
Ghost cell glaucoma is a relatively rare disease, and reports on large-scale clinical trials and the development of new treatments are limited. In recent years, with the improvement in the safety of vitrectomy and the increase in vitreous hemorrhage due to retinal diseases, standardization of diagnostic and treatment methods has become increasingly important.
