Glaucoma associated with retinal detachment is a general term for secondary glaucoma that occurs due to retinal detachment itself or surgery for retinal detachment. It is not a single disease entity but encompasses multiple conditions with different mechanisms of intraocular pressure elevation.
In the Glaucoma Clinical Practice Guidelines (5th edition), the conditions included in this disease group are described across multiple classification categories1).
The European Glaucoma Society Guidelines (5th edition) also describe glaucoma related to vitreoretinal surgery (II.2.3.3.3), stating that long-standing retinal detachment can induce ischemic neovascularization, and the trabecular meshwork can be obstructed by neovascularization, scarring, pigment dispersion, inflammation, and cellular debris from photoreceptor outer segments (Schwartz syndrome)2).
The main conditions included in this disease group are shown below.
| Condition | Glaucoma Classification | Main Mechanism | Typical Onset Timing |
|---|---|---|---|
| Schwartz syndrome | Secondary open-angle | Trabecular meshwork obstruction by photoreceptor outer segments | After RD onset to several weeks |
| Ghost cell glaucoma | Secondary open-angle | Trabecular obstruction by degenerated red blood cells | 1 to 3 months after vitreous hemorrhage |
| Angle rotation glaucoma | Secondary angle-closure | Angle closure due to ciliary body edema | Early after scleral buckling surgery |
| SO glaucoma (anterior chamber migration type) | Secondary angle-closure | Silicone oil (SO) pupillary block | Early to mid postoperative period |
| SO glaucoma (emulsified SO type) | Secondary open-angle | Trabecular obstruction by emulsified SO particles | Several months or more after surgery |
| Inflammatory intraocular pressure elevation | Secondary open-angle | TM obstruction by fibrin and inflammatory debris | Early postoperative period |
| Neovascular glaucoma | Secondary angle-closure | Angle closure due to retinal ischemia-induced neovascularization | Several weeks postoperatively and later |
In rhegmatogenous retinal detachment, intraocular pressure tends to decrease due to the pump action of the exposed retinal pigment epithelium (RPE) 7). Clinically, it is important that this group of diseases causes an increase in intraocular pressure contrary to this principle.
In typical rhegmatogenous retinal detachment, intraocular pressure decreases because the exposed retinal pigment epithelium (RPE) actively absorbs fluid 7). However, in Schwartz syndrome, photoreceptor outer segments shed from the detached retina obstruct the trabecular meshwork, and in ghost cell glaucoma, degenerated red blood cells similarly obstruct it. Additionally, silicone oil or gas used in surgery can cause pupillary block or trabecular meshwork obstruction. When these obstructive mechanisms outweigh the RPE pump effect, intraocular pressure rises.
The subjective symptoms of this disease group are a mixture of those originating from retinal detachment and those from elevated intraocular pressure.
Symptoms associated with retinal detachment:
Symptoms associated with elevated intraocular pressure:
In secondary angle-closure glaucoma (e.g., angle rotation after scleral buckling surgery), visual acuity often declines rapidly with acute intraocular pressure elevation. In ghost cell glaucoma, visual loss due to vitreous hemorrhage precedes the intraocular pressure elevation, which occurs some time after the hemorrhage.
Since characteristic clinical findings differ by pathology, important findings for differential diagnosis are summarized below.
| Pathology | Anterior chamber findings | Angle findings | Other characteristics |
|---|---|---|---|
| Schwartz syndrome | Relatively large cells (photoreceptor outer segments), KP(-) | Open angle | Extreme peripheral small tear, marked intraocular pressure fluctuation |
| Ghost cell glaucoma | Khaki-colored vesicles, pseudohypopyon | Open angle, layered GC deposits inferiorly | History of vitreous hemorrhage |
| Angle rotation | Shallow anterior chamber, ciliochoroidal detachment | Angle closure | After scleral buckling surgery |
| SO glaucoma | SO bubbles in anterior chamber | Open/closed (depending on mechanism) | Accumulation of emulsified SO in superior quadrant |
Characteristics of Schwartz syndrome findings: Unilateral, open-angle. The cell-like floaters in the anterior chamber are photoreceptor outer segments, not inflammatory cells, so keratic precipitates (KP) and iris anterior synechiae are absent. The lack of response to corticosteroids is an important distinguishing feature from uveitis 4). Many small tears are present at the ora serrata or ciliary body, and after some time, strand-like material appears under the detached retina. Lens abnormalities (cataract, dislocation, etc.) may also be present.
Characteristics of ghost cell glaucoma findings: Khaki-colored (tan) spherical vesicles are seen in the anterior chamber and vitreous; when abundant, they form a pseudohypopyon 6). When fresh red blood cells and ghost cells coexist, a heavier layer of fresh red blood cells settles inferiorly and a lighter khaki-colored ghost cell layer settles superiorly, creating a “candy stripe” appearance. On gonioscopy, ghost cells deposit in layers on the lower trabecular meshwork 2).
Findings related to silicone oil: In eyes with silicone oil for several months or longer, emulsified silicone oil particles are partially phagocytosed by macrophages and accumulate in the trabecular meshwork of the superior quadrant, inducing trabeculitis 2).
Each pathological condition in this disease group causes elevated intraocular pressure through different mechanisms.
Schwartz syndrome: Photoreceptor outer segments shed into the subretinal space due to rhegmatogenous retinal detachment pass through the retinal tear along with viscous subretinal fluid, reach the anterior chamber, and obstruct the trabecular meshwork 4)5).
Ghost cell glaucoma: Red blood cells that remain in the vitreous for several weeks or more after vitreous hemorrhage degenerate and become hollow ghost cells with almost all components except the cell membrane lost. These ghost cells have poor deformability, making it difficult for them to pass through the trabecular meshwork, leading to elevated intraocular pressure 6). Onset requires both retention of red blood cells in the vitreous for several weeks and disruption of the anterior hyaloid face (communication between the vitreous and anterior chamber); ghost cell glaucoma rarely occurs from hyphema alone.
Angle rotation glaucoma: Following ciliochoroidal detachment after scleral buckling surgery, the ciliary body rotates forward around the scleral spur as an axis, occluding the angle. This is caused by compression of the vortex veins by the buckle or extensive buckle placement.
Silicone oil glaucoma: The mechanism differs in stages: trabecular meshwork obstruction due to silicone oil migration into the anterior chamber (early), trabeculitis from emulsified silicone oil (intermediate), and permanent structural changes from prolonged contact between silicone oil and trabecular meshwork (late) 2). Overfill of silicone oil is the main cause of early intraocular pressure elevation.
Inflammatory intraocular pressure elevation: Inflammatory reaction and fibrin deposition in the early post-vitrectomy period disrupt the blood-ocular barrier, and inflammatory debris obstructs the trabecular meshwork. This is particularly strong after surgery for proliferative vitreoretinopathy.
Neovascular glaucoma: Secondary to long-standing retinal detachment or retinal ischemia, increased VEGF leads to neovascularization of the iris and angle, occluding the angle 2).
| Procedure/Pathology | Main risk factors |
|---|---|
| After vitrectomy | Combined buckling, intraoperative scatter photocoagulation, PVR |
| After scleral buckling | Narrow angle, encircling band, high myopia, advanced age |
| Silicone oil | Pre-existing glaucoma, diabetes, aphakia 2) |
| Gas tamponade | High concentration use (C3F8), combined photocoagulation |
| Schwartz syndrome | Young males, blunt trauma, atopic dermatitis4) |
The most important step in diagnosing this group of diseases is to differentiate between open-angle and closed-angle mechanisms by gonioscopy, as this directly determines the treatment strategy.
Schwartz syndrome: Confirmation of rhegmatogenous retinal detachment is key to diagnosis. It is clinically diagnosed by a combination of three clinical findings: (1) anterior chamber cells without other signs of uveitis, (2) high intraocular pressure with marked fluctuations, and (3) rhegmatogenous retinal detachment 4). Detection of the tear is often difficult due to poor mydriasis or lens disease; B-mode ultrasound, UBM, and OCT are useful.
Ghost cell glaucoma: Definitive diagnosis is possible by microscopic examination of anterior chamber aspirate. Phase-contrast microscopy reveals spherical ghost cells with degenerated hemoglobin residues (Heinz bodies) inside the cell membrane 6). Suspect this disease when intraocular pressure rises after a history of vitreous hemorrhage.
Secondary angle-closure glaucoma (including angle rotation): Elucidate the pathology by gonioscopy during intraocular pressure elevation and anterior segment findings. Diagnosis may be confirmed when angle findings change during follow-up.
| Disease Pair for Differentiation | Key Points for Differentiation |
|---|---|
| Schwartz syndrome vs Iritis | No KP or anterior synechiae, no steroid response |
| Schwartz syndrome vs Traumatic glaucoma | Presence or absence of intraocular pressure normalization after retinal reattachment |
| Ghost cell glaucoma vs Neovascular glaucoma | Presence or absence of angle neovascularization, color of anterior chamber cells |
| Angle rotation vs Malignant glaucoma | Ciliary body position on UBM and aqueous humor dynamics in the vitreous cavity |
In ghost cell glaucoma, the angle is open and khaki-colored (earth-brown) ghost cells are observed in the anterior chamber. In contrast, neovascular glaucoma shows neovascularization in the angle, and as it progresses, the angle becomes closed. Particularly in patients with a history of diabetic retinopathy or retinal vein occlusion who have had vitreous hemorrhage, neovascular glaucoma should always be considered in the differential diagnosis 6). Gonioscopy is essential for differentiation.
The treatment of secondary glaucoma should prioritize treating the underlying cause whenever possible 1). In secondary glaucoma, the mechanism of intraocular pressure elevation should be understood to select the appropriate treatment. Since treatment strategies vary greatly depending on the pathology in this disease group, accurate pathological diagnosis is a prerequisite.
Principle: Retinal reattachment is the first-line treatment.
Corticosteroids are ineffective. Since the “cells” in the anterior chamber are photoreceptor outer segments, not inflammatory cells, the anti-inflammatory effect of steroids does not work. Continuing steroid treatment under a misdiagnosis of uveitis will not lead to improvement and may increase the risk of steroid-induced glaucoma.
For intraocular pressure management while awaiting surgery, temporary pressure reduction can be achieved with carbonic anhydrase inhibitors (acetazolamide 500 mg twice daily orally) or beta-blockers (timolol 0.5%) eye drops 4).
Prognosis: Intraocular pressure normalizes after retinal reattachment. Postoperative pressure-lowering medications are rarely needed.
Medical therapy (first step):
If intraocular pressure reduction is sufficient, consider discontinuing in the order of ripasudil first, then latanoprost. Ripasudil is a Rho kinase inhibitor and may be effective against trabecular meshwork obstruction by ghost cells due to its mechanism of action.
Surgical treatment (second step):
Refractory cases (third step):
Treatment for angle closure due to ciliary body edema after scleral buckling surgery is described below.
Angle closure due to serous choroidal detachment often resolves spontaneously if the retinal break is closed.
The essence of angle rotation glaucoma is anterior rotation of the ciliary body due to ciliary body edema, causing physical angle closure. Pilocarpine (a miotic) contracts the ciliary muscle, further increasing tension in the edematous ciliary body and worsening angle closure. Therefore, the principle is to promote ciliary body relaxation with mydriatics and wait for spontaneous resolution. Care must be taken not to use miotics casually just because the angle is closed.
Prevention:
Medical therapy: Topical medications including beta-blockers, prostaglandin analogs, and carbonic anhydrase inhibitors can control intraocular pressure in 30–78% of cases.
Silicone oil removal: According to the package insert, it should be removed at an appropriate time within 1 year after retinal stabilization. However, removal may not be possible in cases with high risk of redetachment or concern for phthisis due to hypotony. There are reports of persistent IOP elevation after SO removal, so removal alone does not guarantee IOP control 2).
Surgical therapy (refractory cases):
According to the package insert, it is recommended to remove silicone oil at an appropriate time within one year after the retina has stabilized. Early removal is desirable because intraocular pressure elevation due to emulsified silicone oil can occur after several months. However, removal may not be possible in cases with high risk of redetachment or risk of phthisis bulbi due to hypotony. The decision is made based on a comprehensive assessment of retinal stability and intraocular pressure in each individual case.
Intraocular pressure elevation associated with early postoperative inflammation can often be controlled with a combination of steroid eye drops and aqueous humor suppressants (beta-blockers, carbonic anhydrase inhibitors). However, in steroid responders, steroid eye drops may paradoxically increase intraocular pressure, requiring careful monitoring.
Intraocular gases are expansile: SF6 expands to 2–2.5 times the injected volume, and C3F8 expands to 4 times. Maximum gas expansion is reached approximately 24 hours after injection for SF6 and approximately 72 hours for C3F8, but the expansion rate is highest in the first 6 hours.
Prophylactic administration of IOP-lowering drugs:
Timolol 0.5%/dorzolamide 2% fixed combination eye drops have been shown in RCTs to reduce postoperative intraocular pressure spikes3).
Unexpected expansion can be avoided by adjusting the concentration to 20% or less for SF6 and 12% or less for C3F8.
Treatment of open-angle type
Schwartz syndrome: Retinal reattachment surgery is curative. Steroids are ineffective.
Ghost cell glaucoma: IOP-lowering drugs → anterior chamber washout → PPV → filtering surgery
Inflammatory: Steroid eye drops + aqueous humor suppressants
Emulsified SO type: Medication → SO removal → CPC/drainage
Treatment of angle-closure type
Angle rotation: Mydriatics (pilocarpine contraindicated!) → laser gonioplasty
SO pupillary block: Prevention by inferior iridectomy. SO removal if occurs
Gas expansion: Concentration management + early postoperative IOP check. Prophylactic IOP-lowering drugs considered based on risk 3)
Neovascular glaucoma: Anti-VEGF + PRP + glaucoma surgery
Rhegmatogenous retinal detachment leads to the following cascade 4)5).
Shallow retinal detachment involving the vitreous base particularly increases the risk of this condition. In shallow detachment, continuous shedding of photoreceptor outer segments is promoted, and involvement of the vitreous base disrupts the barrier function of the vitreous membrane, making it easier for photoreceptor outer segments to reach the anterior chamber. Small tears near the ora serrata or pars plana have a short distance to the anterior chamber, resulting in high efficiency of access.
After retinal reattachment, the supply of photoreceptor outer segments ceases, and the outer segments deposited in the trabecular meshwork are removed by phagocytosis of trabecular cells. Therefore, intraocular pressure normalizes postoperatively. This normalization of intraocular pressure is a definitive distinguishing feature from traumatic glaucoma (irreversible structural damage due to angle recession) and primary open-angle glaucoma.
The changes that red blood cells undergo after vitreous hemorrhage are as follows6).
Ghost cells are spherical (unlike the biconcave disc shape of normal red blood cells), appear khaki-colored, and have markedly reduced deformability. Therefore, they cannot pass through the pores of the trabecular meshwork, and when they flow into the anterior chamber in large quantities, aqueous humor outflow resistance increases sharply.
The route of entry into the anterior chamber is the anterior vitreous face (anterior hyaloid membrane) damaged by surgery, trauma, or spontaneous rupture. Without this route, ghost cells cannot reach the anterior chamber, and glaucoma does not develop. Ghost cell glaucoma rarely occurs from anterior chamber hemorrhage alone.
Three stages of mechanisms have been proposed for intraocular pressure elevation due to silicone oil (SO), depending on the timing2).
Early (immediately to weeks after surgery): Migration of SO into the anterior chamber (especially during overfill) directly obstructs the trabecular meshwork. In aphakic eyes, SO easily moves into the anterior chamber, so angle-closure mechanism (pupillary block) is often the main cause.
Intermediate (months after surgery): Emulsified SO particles migrate into the anterior chamber and are partially phagocytosed by macrophages. These complexes accumulate in the trabecular meshwork of the superior quadrant and induce trabeculitis.
Late stage (long-term retention): Long-term contact between SO and the trabecular meshwork leads to permanent structural changes. At this stage, elevated intraocular pressure may persist even after SO removal.
Complications of SO are diverse and include corneal endothelial damage, progression of cataracts, secondary glaucoma due to elevated intraocular pressure, uptake of SO into the optic nerve head, migration of SO into the intracranial space, and toxicity to the retinal pigment epithelium.
After scleral buckling surgery, compression of the vortex veins by the buckle or extensive buckle placement causes ciliary congestion and edema, leading to choroidal detachment. Since the ciliary body is firmly attached to the scleral spur, choroidal detachment causes the ciliary body to rotate forward around the scleral spur (axis), pushing the iris root upward and closing the angle.
Normally, a space for aqueous humor outflow is maintained between the ciliary body and the angle wall, but this forward rotation physically closes the angle.
Immediately after panretinal photocoagulation, ciliary body swelling or temporary breakdown of the blood-retinal barrier causes fluid movement from the choroid to the vitreous, displacing the lens-iris diaphragm forward and closing the angle. The laser energy level affects the incidence and severity.
Open-angle mechanism
Photoreceptor outer segment obstruction: Schwartz syndrome. Tear → vitreous → anterior chamber → TM obstruction
Degenerated red blood cell obstruction: Ghost cell glaucoma. Vitreous hemorrhage → degeneration in weeks → cannot pass through TM
Emulsified SO obstruction: SO particles → phagocytosis by macrophages → accumulation in superior TM → trabeculitis2)
Inflammatory obstruction: TM obstruction by fibrin and debris. Early postoperative period.
Angle-closure mechanism
Angle rotation: Ciliary body edema → forward rotation around scleral spur axis → angle closure
SO pupillary block: SO occludes the pupil → forward displacement of the lens-iris diaphragm
Gas expansion: Pupillary block or aqueous outflow compression due to expanding gas
Neovascularization: Retinal ischemia → VEGF↑ → iris and angle neovascularization → fibrous adhesion
Silicone oil (SO) emulsifies over time, and tiny SO particles migrate into the anterior chamber. These emulsified SO particles are partially phagocytosed by macrophages and accumulate in the trabecular meshwork of the superior quadrant, inducing trabeculitis 2). Furthermore, prolonged contact between SO and the trabecular meshwork can cause permanent structural changes, and intraocular pressure elevation may persist even after SO removal. Therefore, removal within one year is recommended once the retina is stable.
In cases with high risk of expansive gas, pre-existing glaucoma, or postoperative inflammation, omission of the day 1 review should be carefully considered. Even when extending the review interval, gas concentration management and the pathway for consultation in case of intraocular pressure spikes should be clarified in advance.
Benz et al. showed in an RCT of 50 eyes that timolol 0.5%/dorzolamide 2% combination eye drops (administered at the end of surgery) reduced postoperative IOP compared to placebo 3). However, the target and timing of prophylactic administration should be individualized according to the surgical procedure, tamponade, and pre-existing glaucoma risk.
In a population-based study, the cumulative probability of developing glaucoma over 10 years after combined scleral buckling and vitrectomy or vitrectomy alone was 8.9% (95% CI 3.8–14%), significantly higher than 1.0% (95% CI 0–2.4%) in the control group (P=0.02) 8). However, another retrospective study of 111 eyes with a mean follow-up of 49 months found no long-term intraocular pressure elevation, showing discrepancies between reports.
