Glaucoma after keratoplasty is a general term for elevated intraocular pressure and associated optic nerve damage that occur after corneal transplant surgery. It is classified as a type of secondary glaucoma. Surgical techniques include penetrating keratoplasty (PKP), deep anterior lamellar keratoplasty (DALK), and corneal endothelial transplantation (Descemet stripping automated endothelial keratoplasty: DSAEK, Descemet membrane endothelial keratoplasty: DMEK), each with different risks and mechanisms of intraocular pressure elevation.
Elevated intraocular pressure is observed in approximately 20–30% of cases after PKP. In patients with a history of glaucoma before surgery, the frequency of postoperative intraocular pressure elevation is even higher. The incidence of glaucoma after DSAEK/DMEK is lower than after PKP; a meta-analysis showed no significant difference between surgical techniques at 12 months, with 4/152 eyes (2.6%) in the DMEK group and 4/148 eyes (2.7%) in the UT-DSAEK group (risk difference 0.00, 95% CI −0.04 to 0.04)2).
The differences in glaucoma risk by surgical technique are shown below.
| Surgical technique | Glaucoma risk | Characteristics |
|---|---|---|
| PKP | High (20–30%) | Extensive anterior chamber manipulation, high risk of PAS formation |
| DALK | Low | No anterior chamber manipulation, only steroid-induced glaucoma |
| DSAEK | Low to moderate | Small incision, long-term steroid use |
| DMEK | Low to moderate | Beware of air pupillary block |
In PKP, extensive intra-anterior chamber manipulation makes peripheral anterior synechia (PAS) and postoperative inflammation common causes. In DALK, since there is no anterior chamber manipulation, secondary glaucoma other than steroid-induced glaucoma usually does not occur. DSAEK/DMEK are small-incision surgeries with fewer suture-related complications and lower rejection rates compared to PKP. However, steroid eye drops are continued for about one year postoperatively, so the risk of steroid-induced glaucoma remains.
Rejection rates after corneal transplantation vary by surgical technique. In a comparison of surgical outcomes for Fuchs endothelial corneal dystrophy and pseudophakic bullous keratopathy, rejection rates at one year were reported as PK 17%, DSAEK 2–9%, and DMEK 0–6% 1). Five-year graft survival rates were 95% for Fuchs (equivalent for PK and DSAEK) and 73% for PBK (equivalent for PK and DSAEK) 1).
After PKP, approximately 20–30% of patients experience elevated intraocular pressure. The risk is even higher if glaucoma was present before surgery. On the other hand, with endothelial keratoplasty such as DSAEK/DMEK, the incidence of glaucoma is only about 2–3%, which is lower than with PKP 2). Regardless of the surgical technique, long-term use of steroid eye drops is required, so caution is needed for steroid-induced glaucoma.
In mild to moderate open-angle type with elevated intraocular pressure, there are almost no subjective symptoms in the early stage. It is often only when glaucoma progresses and visual field defects occur that patients become aware of visual field loss or scotomas.
In acute angle-closure type, the following symptoms appear:
As corneal graft opacity or edema progresses, it can cause vision loss independent of glaucoma.
In corneal transplant eyes, slit-lamp findings and visual field assessment may be limited due to graft opacity, irregular astigmatism, and suture effects. After corneal surgery, changes in corneal shape can make intraocular pressure measurement and visual field testing difficult, and attention should also be paid to optic nerve changes associated with sustained high intraocular pressure.
It is classified into four types based on the mechanism of intraocular pressure elevation.
Retained Ophthalmic Viscosurgical Device
Timing: Immediately after surgery (hours to days)
Mechanism: Retained ophthalmic viscosurgical devices (e.g., hyaluronic acid) in the anterior chamber physically obstruct the trabecular meshwork. Transient and manageable with conservative treatment.
Inflammatory Open-Angle
Timing: Early to mid postoperative period
Mechanism: Inflammatory cells and cytokines increase aqueous outflow resistance in the trabecular meshwork. This corresponds to secondary open-angle glaucoma.
Angle Closure
Timing: Any time after surgery
Mechanism: Suture-induced distortion and inflammation lead to PAS formation, causing angle closure. The more extensive the anterior chamber manipulation during PKP, the higher the frequency of occurrence.
Steroid-Induced Glaucoma
Timing: During steroid use
Mechanism: Steroids enhance extracellular matrix production in trabecular meshwork cells, altering the cytoskeleton and increasing aqueous outflow resistance. Open-angle type.
The basic diagnostic approach is the same as for general glaucoma. However, in corneal transplant eyes, accurate intraocular pressure measurement is often difficult due to ocular surface irregularities, so multiple measurement methods should be combined for comprehensive evaluation.
In corneal transplant eyes, interpretation of intraocular pressure values is difficult for the following reasons.
Recommended approach: comprehensively evaluate results from multiple methods such as non-contact tonometry (NCT), GAT, Tono-Pen, and palpation. The following devices have been reported as alternative intraocular pressure measurement methods for diseased and postoperative corneas 1).
| Measurement method | Characteristics |
|---|---|
| Pneumotonometer | Uses a 5 mm silicone tip, adapts to the cornea |
| ORA (ocular response analyzer) | IOP calculation corrected for corneal biomechanical properties |
| Dynamic contour tonometer (DCT) | Minimizes the influence of corneal properties |
| Rebound tonometer | No need for topical anesthesia, uses a small probe |
It is important to use the same measurement method over time to detect clinically significant IOP fluctuations1).
Differentiating steroid-induced glaucoma from inflammatory secondary glaucoma is clinically important. Differentiation is made by checking the change in IOP after reducing or discontinuing steroid eye drops.
| Pathophysiology | Key points for differentiation |
|---|---|
| Steroid-induced glaucoma | IOP decreases with steroid reduction or discontinuation |
| Inflammatory open-angle glaucoma | Improves with anti-inflammatory treatment; angle is open |
| Angle-closure glaucoma | Gonioscopy confirms PAS or closure |
| Corneal edema due to graft failure | Assess whether elevated IOP is cause or result |
After corneal transplantation, corneal thickness and shape change, reducing the accuracy of standard Goldmann applanation tonometry. Increased corneal thickness leads to overestimation of IOP, and irregular astigmatism distorts the mires, making accurate measurement difficult. Therefore, multiple methods such as non-contact tonometry, Tono-Pen, and palpation are used in combination for comprehensive evaluation. Recently, methods that correct for the influence of corneal biomechanical properties, such as the Ocular Response Analyzer (ORA) and dynamic contour tonometry (DCT), have become available 1).
Treatment strategies differ depending on the mechanism of IOP elevation. A stepwise approach is described below.
If caused by residual viscoelastic material in the anterior chamber or intraocular inflammation, conservative management with glaucoma eye drops or oral carbonic anhydrase inhibitors (CAIs) is used. In most cases, it is transient and improves with spontaneous absorption of the viscoelastic material.
Glaucoma eye drops after corneal transplantation require caution because they are more likely to cause side effects than in routine glaucoma treatment.
| Drug class | Risks and precautions |
|---|---|
| Beta-blockers | High incidence of corneal epithelial disorders |
| Prostaglandin analogs | Concerns about intraocular inflammation, rejection, and herpes recurrence |
| CAI eye drops | Effect on corneal endothelium → risk of corneal edema |
| Oral CAIs | Relatively safe to use |
| Alpha-2 agonists | No specific contraindications for corneal transplant eyes |
Prostaglandin (PG) preparations have traditionally been noted for concerns of inducing intraocular inflammation or graft rejection. However, recent large-scale database studies (10 facilities, 40,024 cases) reported that the incidence of uveitis in the PGA group was 0.3%, which was the lowest compared to the beta-blocker group (2.0%), alpha-agonist group (1.6%), and CAI group (1.7%) (multivariate logistic regression with PGA group as reference: beta-blocker OR 6.44, 95% CI 5.08–8.16) 4). However, this study was not limited to corneal transplant eyes, and careful case-by-case judgment is required regarding the association between PG preparations and rejection in corneal transplant eyes.
When steroid-induced glaucoma is diagnosed, the following steps should be considered sequentially:
However, after corneal transplantation, prevention of rejection is necessary, and reducing steroids may be difficult depending on the condition of the primary disease. In steroid-induced glaucoma, the trabecular meshwork accounts for a large proportion of aqueous outflow resistance, so outflow reconstruction surgery or selective laser trabeculoplasty (SLT) is considered to be effective.
Surgery is considered when adequate intraocular pressure control cannot be achieved with medication.
Indications include cases where trabeculectomy with antimetabolites has failed, cases with severe conjunctival scarring due to previous surgery, and cases where trabeculectomy is unlikely to succeed (recommendation level 1B) 5).
Three types of Baerveldt glaucoma implants (BG101-350, BG102-350, BG103-250) and two types of Ahmed glaucoma valves (FP7, FP8) are approved 5). To prevent postoperative tube exposure, the tube must be covered with patch materials such as preserved sclera or preserved cornea (recommendation level 1A) 5).
In the Ahmed Baerveldt Comparison Study (ABC Study), the 5-year cumulative success rate was 44.7% in the Ahmed group and 39.4% in the Baerveldt group. The Baerveldt group required additional glaucoma surgery less frequently, but hypotony-related complications were slightly more common in the Baerveldt group 7). The Ahmed Versus Baerveldt Study (AVB Study) also reported nearly equivalent 5-year outcomes, with success rates of 31.3% in the Ahmed group and 36.6% in the Baerveldt group 8).
The 2-year success rate of Baerveldt implantation in glaucoma eyes secondary to uveitis has been reported as 91.7%. Corneal graft failure was observed as a complication in 8.3% of cases 6). The 2-year success rate of Ahmed valve implantation for uveitis-related glaucoma was 68.4%, and corneal endothelial damage due to contact between the tube and cornea has been reported 6).
When placing a tube shunt in an eye with a corneal graft, there is a risk of corneal endothelial damage because the tube runs near the graft. The indication should be determined considering the impact on long-term graft survival.
This is considered when intraocular pressure control cannot be achieved with any of the above treatments. Cyclophotocoagulation using a semiconductor laser or cryocoagulation is performed. It is positioned as a last resort due to the risk of vision loss.
In eyes with corneal grafts, each drug class has specific risks. Beta-blockers frequently cause corneal epithelial damage, prostaglandin analogs raise concerns about rejection and herpes recurrence, and CAI eye drops have been reported to cause corneal edema due to effects on the corneal endothelium. Oral CAIs (e.g., acetazolamide) can be used relatively safely. Drug selection should be individualized based on graft condition, corneal endothelial cell density, and history of rejection.
Intraocular pressure elevation after PKP occurs through different mechanisms depending on the time period.
1. Immediate postoperative period (hours to days): Viscoelastic substances (e.g., sodium hyaluronate) remain in the anterior chamber and physically obstruct the trabecular meshwork spaces. This is usually transient and resolves spontaneously if anterior chamber washout is not required.
2. Early to intermediate postoperative period (days to weeks): Surgical trauma disrupts the blood-aqueous barrier, causing inflammatory cells and proteins to enter the anterior chamber, leading to deposition on the trabecular meshwork and obstruction of its spaces. Inflammatory mediators such as prostaglandins also increase aqueous outflow resistance. This corresponds to the pathophysiology of secondary open-angle glaucoma.
3. Any time after surgery: Distortion between the iris and cornea due to sutures after PKP, along with formation of posterior synechiae from chronic inflammation, leads to progression of peripheral anterior synechiae (PAS) and organic angle closure. Because PKP involves full-thickness incisions and sutures, the anterior chamber morphology is prone to change postoperatively.
4. Long-term postoperative period (during steroid use): Corticosteroids enhance extracellular matrix production in trabecular meshwork cells and alter the cytoskeleton, increasing aqueous outflow resistance. Individual susceptibility varies, and it is more common in children and the elderly. Steroid-induced glaucoma presents as an open-angle type.
DSAEK/DMEK are small-incision surgeries with limited anterior chamber manipulation compared to PKP, so the risk of PAS formation and inflammatory intraocular pressure elevation is lower. However, the following specific mechanisms exist:
Persistent intraocular pressure elevation increases the load on corneal endothelial cells, reducing graft endothelial function and causing corneal edema. Corneal edema further reduces the accuracy of intraocular pressure measurement, making appropriate pressure management difficult. In addition, surgical treatment for glaucoma (especially tube shunt surgery) involves manipulation near the graft, which may worsen graft failure postoperatively. Balancing intraocular pressure control and graft survival is the greatest clinical challenge in this condition.
Treatment outcomes of surgical procedures are poorer compared to primary glaucoma. Multiple surgical interventions may be required, and cyclophotocoagulation or cryocoagulation may be the last resort. Even if intraocular pressure is controlled, graft failure is not uncommon, and some cases require regrafting.
