Penetrating keratoplasty (PKP) is a surgery in which the diseased full-thickness cornea is excised and replaced with a full-thickness donor corneal graft. Typically, a central circular corneal button 7.0–8.5 mm in diameter is removed and exchanged with a corresponding donor cornea2). The most common goal is vision improvement, but restoring structural support for thinned or perforated corneas is also an important indication.
PKP has the longest history among corneal transplant surgeries. In a 2012 worldwide survey, PK was the predominant corneal transplant procedure globally 3). In recent years, with the spread of deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK), the number of PK procedures has been decreasing 1, 7).
QWhat is the difference between penetrating keratoplasty and lamellar keratoplasty?
A
Penetrating keratoplasty replaces the full thickness of the cornea, whereas lamellar keratoplasty replaces only a portion of the corneal layers. Lamellar keratoplasty includes deep anterior lamellar keratoplasty (replacing the anterior stroma) and endothelial keratoplasty (replacing only the endothelium). Deep anterior lamellar keratoplasty does not transplant donor endothelium, so endothelial rejection does not occur. Endothelial keratoplasty is a procedure specialized for endothelial dysfunction. Penetrating keratoplasty is indicated for cases that cannot be managed with lamellar transplantation, such as full-thickness corneal opacities or severe shape abnormalities.
Corneal findings vary depending on the underlying disease, but the following are representative.
Corneal opacity: Stromal scarring, edematous opacity due to endothelial failure, deposits from corneal dystrophy.
Corneal thinning or protrusion: Seen in ectatic diseases such as keratoconus.
Corneal perforation: Associated with infectious ulcers or autoimmune diseases.
Corneal neovascularization: Seen in inflammatory diseases or herpetic keratitis. Vascular invasion of two or more quadrants is a high-risk factor for rejection.
Rejection after PKP commonly occurs 6 months to 1 year postoperatively. The incidence of endothelial rejection varies by underlying disease but is approximately 10–30%. Sudden blurred vision, decreased visual acuity, and photophobia are important subjective symptoms.
Indications for penetrating keratoplasty are broadly classified into three categories.
Optical keratoplasty
Bullous keratopathy: Fuchs endothelial corneal dystrophy and pseudophakic bullous keratopathy are typical indications. Many patients achieve significant visual improvement after PK 2)
Keratoconus: Indicated when functional vision cannot be achieved with glasses or contact lenses 1). Persistent corneal edema after acute hydrops is also an indication for full-thickness transplantation 1)
Corneal leukoma: Indicated when visual impairment results from scarring after infection or trauma
Corneal dystrophy: Cases presenting with full-thickness opacities such as lattice, granular, or macular corneal dystrophy
Therapeutic and tectonic keratoplasty
Therapeutic keratoplasty: Performed to remove the lesion in corneal infections resistant to medical treatment. The recurrence rate is reported to be 20%, and confocal microscopy and wide margin clearance are recommended.
Tectonic keratoplasty: Performed to maintain the shape of the eyeball in cases of corneal perforation.
Corneoscleral transplantation: In cases where infection extends beyond the limbus or there is severe peripheral thinning (eccentric keratoconus, pellucid marginal degeneration, keratoglobus), a large corneoscleral graft is required.
PKP may be contraindicated in cases of multiple failed full-thickness corneal transplants or extensive anterior segment scarring 1). Surgery becomes difficult if corneal thinning extends near the limbus, increasing the risk of failure 1).
Corneal neovascularization: Cases with vascular invasion into the stroma in two or more quadrants are high-risk.
Regraft cases: Cases with a history of rejection are at even higher risk.
History of herpes keratitis: Postoperatively, increased steroids or additional antiviral medication may be required.
Comorbid glaucoma: Postoperative management becomes more complex.
Presence of intraocular inflammation: Active inflammation such as uveitis increases the risk of rejection.
QIn what cases is full-thickness corneal transplantation necessary?
A
PKP is necessary when there is opacity involving the full thickness of the cornea, or when both the endothelium and stroma are damaged. If only the corneal endothelium is damaged, EK (endothelial keratoplasty) is often chosen; if only the corneal stroma is opaque, DALK (deep anterior lamellar keratoplasty) is often selected. Also, PKP is the first choice in cases with deep stromal scars where perforation is likely during DALK, or in cases of corneal perforation or uncontrollable corneal infection.
Slit-lamp microscopy: Evaluate the extent and depth of corneal opacity, presence of angle synechiae, and limbal function (Vogt’s palisades, vascular invasion).
Anterior segment OCT: Non-invasively assess the depth and extent of corneal opacity. Also useful for measuring corneal thickness.
Specular microscopy: Check corneal endothelial cell density and morphology to guide surgical technique selection.
Fundus evaluation: Rule out concurrent lens opacity or fundus disease, and assess the potential for visual improvement after surgery.
Tear film evaluation: Perform Schirmer test and fluorescein staining to assess the ocular surface. Reduced tear volume increases the risk of postoperative epithelial defects.
Visual field testing: Perform if visual field abnormalities cannot be ruled out.
Selection Criteria for Penetrating Keratoplasty vs. Lamellar Keratoplasty
Retrobulbar and lid akinesia anesthesia are used to stop eye movement, and a Honan balloon is used to sufficiently lower vitreous pressure. General anesthesia is recommended for simultaneous cataract surgery or pediatric cases. A Flieringa ring is sutured to the sclera to prevent globe collapse.
The donor corneal button is created 0.25–0.5 mm larger than the host cornea. It is prepared from the endothelial side, incised to about 4/5 of the corneal depth with a trephine, and then entered into the anterior chamber with a blade. For suturing the donor cornea, 10-0 nylon is used, with 8 interrupted sutures and 16 continuous sutures, or 24 continuous sutures.
In keratoconus, a donor of the same size as the host may be used in anticipation of future graft steepening. In microbial keratitis, the trephine size is chosen to surround the entire lesion.
Steroid eye drops: Betamethasone 0.1% started at 4–5 times daily, changed to low-concentration steroid (fluorometholone 0.1%) after about 6 months and continued
Antibiotics: Levofloxacin 1.5% started at 5 times daily, tapered and discontinued after epithelial stabilization. Systemic administration for a few days from the day of surgery
Cyclosporine eye drops and oral administration: Used in combination
Cases with vascular invasion in 2 or more quadrants, regrafts, etc., are high-risk.
Systemic steroid administration: Start intravenous infusion of Rinderon 4–8 mg during surgery, switch to oral prednisolone, and taper over 2 weeks
Immunosuppressants: Start oral cyclosporine at 2–3 mg/kg/day, maintain trough level at 70–100 ng/mL, and continue for about 6 months. Regular monitoring of renal function is necessary
Steroid eye drops: Continue betamethasone 0.1% 4 times daily for at least 1 year, then taper
Poor graft centration: Deviation from the visual axis affects postoperative visual acuity.
Irregular trephination: Irregular incisions affect wound closure and astigmatism.
Choroidal hemorrhage/effusion: General anesthesia can reduce the risk of occurrence.
Lens damage: May occur during trephine insertion.
Vitreous prolapse: Prolapse of vitreous into the anterior chamber complicates postoperative management.
Postoperative Complications
Rejection: Endothelial rejection is clinically most important; delayed detection leads to irreversible graft failure.
Glaucoma: Caused by peripheral anterior synechiae due to anterior chamber manipulation, postoperative inflammation, and steroid-induced glaucoma.
Infection: Includes suture-related infections and opportunistic infections (bacterial, fungal, herpetic) associated with long-term steroid use.
Astigmatism: Irregular astigmatism is the most common postoperative refractive error, often requiring contact lens wear2).
Wound dehiscence: Occurs in 1.3–5.8% of cases, leading to structural weakness of the globe.
Complications of PK include infection, rejection, graft failure, glaucoma, cataract, and poor refractive outcomes (anisometropia, high corneal astigmatism)1).
After PKP, long-term use of postoperative steroid eye drops can accelerate posterior subcapsular cataract (PSC), sometimes requiring cataract surgery5). Be aware of unique challenges different from routine cataract surgery.
Difficulty in IOL power calculation: After PKP, suture tension heterogeneity and wound healing process cause high astigmatism (mean keratometric astigmatism after suture removal: 3.70±3.20 D), reducing predictability of IOL power calculation6). It is advisable to remove all corneal sutures before cataract surgery and calculate IOL power after corneal curvature stabilizes. If the cornea is opaque, measure axial length using A-mode ultrasound.
Surgical approach and endothelial protection: The scleral tunnel approach can minimize impact on the graft margin. When using a corneal incision, care should be taken not to extend it near the graft margin. Use the soft-shell technique with a dispersive viscoelastic to protect the graft endothelium, and ensure sufficient distance from the endothelium when using ultrasound energy 5).
Astigmatism management: For regular astigmatism, a toric IOL is an option, but its effect is limited for irregular astigmatism. Corneal relaxing incisions (CRI) can be performed within the graft-host junction 6).
Triple procedure (simultaneous PKP and cataract surgery): In cases with advanced cataract and need for corneal transplantation, simultaneous surgery is considered. Perform phacoemulsification before PK if visibility allows, to reduce open-sky time. When performing continuous curvilinear capsulorhexis through a cloudy cornea, capsular staining agents such as trypan blue are useful 5). Staged surgery has the advantage of less refractive error after graft stability.
QWhat happens if rejection occurs?
A
When rejection occurs, redness, blurred vision, decreased vision, and eye pain appear acutely. Linear deposits called Khodadoust line and Descemet membrane folds are seen on the corneal endothelium. If detected early and treated with intensive steroids, rejection can be suppressed in many cases. However, if treatment is delayed, endothelial cells are irreversibly damaged and the graft fails. Even if rejection resolves, it adversely affects long-term graft survival.
QWhat precautions are needed after surgery?
A
The most important thing after surgery is to continue steroid eye drops as instructed. If sudden redness, blurred vision, decreased vision, or eye pain occurs, it may indicate rejection, so seek medical attention promptly. If you notice loose sutures, also seek immediate care. Avoid rubbing your eyes and physical trauma such as bumps. During long-term steroid use, monitoring for elevated intraocular pressure is essential.
Graft survival rates for PK vary greatly depending on the underlying disease.
According to the Australian Corneal Graft Registry, long-term survival of PK for corneal ectasia is reported as 95% at 5 years and 89% at 10 years 1).
10-year survival is highest for keratoconus, followed by post-infectious scarring, and worst for inflammatory diseases such as Stevens-Johnson syndrome and ocular pemphigoid.
PK for Fuchs corneal endothelial dystrophy achieves significant visual improvement in many patients, but the risk of intraoperative choroidal hemorrhage is high, and the postoperative rejection risk and time to visual recovery are longer than with EK 2).
The Cornea Donor Study (CDS) compared long-term outcomes of PK for FECD and pseudophakic corneal edema using older donors (66–75 years) versus younger donors (1,090 patients, prospective multicenter double-blind noninferiority trial) 4). The 5-year graft survival rate was identical at 86% in both groups, and at 10 years there was no significant difference (77% in the younger group vs. 71% in the older group). Donor corneas up to age 75 were shown to be safe for PK, but older donor tissue had slightly greater postoperative endothelial cell loss (at 5 years: 824 cells/mm² in the younger group vs. 654 cells/mm² in the older group), and in the oldest age group (72–75 years), graft survival decreased markedly after 6 years 4).
The cornea is an avascular tissue and has historically been considered to have immune privilege. However, PK involves transplantation of full-thickness tissue including epithelium, stroma, and endothelium, making it more susceptible to rejection than lamellar transplantation 7). Rejection can contribute to graft failure.
There are three types of rejection: epithelial, stromal, and endothelial. Clinically, endothelial rejection is the most frequent and important.
Epithelial rejection: Associated with replacement of graft epithelium, with subepithelial infiltrates. Relatively mild and has a good prognosis.
Stromal rejection: Cellular infiltration into the stroma. Reported incidence is 2–12% 1).
Endothelial rejection: Characterized by a rejection line (Khodadoust line), keratic precipitates, Descemet membrane folds, and stromal edema. If detection is delayed, graft function may be irreversibly lost.
Graft failure in PK occurs due to different causes over time. In the early period (within a few years after surgery), rejection is the main cause; in the late period, endothelial failure due to age-related loss of donor endothelial cells becomes the main cause.
Loose sutures can become a source of infection or trigger rejection, so they should be removed promptly upon detection.
Meta-analyses have shown that the rejection rate of deep anterior lamellar keratoplasty is significantly lower than that of penetrating keratoplasty (odds ratio 0.28; 95% confidence interval 0.15–0.50; P < 0.001). Meanwhile, the graft failure rate is similar between the two procedures (odds ratio 1.05; 95% confidence interval 0.81–1.36) 1).
Improvements in contact lens design and the widespread use of collagen cross-linking (CXL) have also contributed to the decrease in penetrating keratoplasty for corneal ectasia1). According to data from the Eye Bank Association of America (EBAA), corneal transplantation for keratoconus has been steadily declining from 2011 to 2022 1).
Femtosecond laser-assisted keratoplasty (FLAK) is a technique in which trephination is performed using a femtosecond laser on both the donor and recipient. Theoretically, it is expected to improve wound strength, allow earlier suture removal, shorten visual rehabilitation, and reduce astigmatism, but no long-term advantage over mechanical trephination has been demonstrated 1).
PK has been reported to be a safe and effective procedure with good visual outcomes for all severities of keratoconus. Suture technique does not affect outcomes, but a smaller size difference between graft and host results in less myopic shift 1).
American Academy of Ophthalmology Corneal Ectasia Preferred Practice Pattern Panel. Corneal Ectasia Preferred Practice Pattern. Ophthalmology. 2024.
Ní Dhubhghaill SS, Patel DV, Campbell P, et al. Fuchs endothelial corneal dystrophy: a review. Clin Exp Ophthalmol. 2021.
Gain P, Jullienne R, He Z, et al. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol. 2016;134(2):167-173. doi:10.1001/jamaophthalmol.2015.4776.
Mannis MJ, Holland EJ, Gal RL, et al. The effect of donor age on penetrating keratoplasty for endothelial disease: graft survival after 10 years in the Cornea Donor Study. Ophthalmology. 2013;120(12):2419-2427. PMID: 24246825.
Olson RJ, Braga-Mele R, Chen SH, et al. Cataract in the Adult Eye Preferred Practice Pattern. Ophthalmology. 2022;129:P52-P142.
Koffler BH, Claman DQ, Heidemann DG, et al. Corneal Edema and Opacification Preferred Practice Pattern. Ophthalmology. 2024;131:P1-P56.
Liu S, Wong YL, Walkden A. Current perspectives on corneal transplantation. Clin Ophthalmol. 2022;16:631-646. doi:10.2147/OPTH.S289359. PMID: 35282172.
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