Penetrating Keratoplasty

From EyeWiki

All content on Eyewiki is protected by copyright law and the Terms of Service. This content may not be reproduced, copied, or put into any artificial intelligence program, including large language and generative AI models, without permission from the Academy.

Article initiated by:
Ana Bartolomei MD
All contributors:
John Reid Burns, Steven Yang, Brad H. Feldman, M.D., Gary L. Legault, MD, Erik Anderson, MD, Alex Kozak, Maria A. Woodward, MD, Colleen Halfpenny, M.D., Anna Murchison, MD, MPH, Zeba A. Syed, MD, Grant A. Justin, MD, Ana Bartolomei MD, Evan Wotipka, MD, Maria D. Bernal, MD, Tian Yang
Assigned editor:
Gary L. Legault, MD, Maria D. Bernal, MD
Review:
Assigned status Up to Date
 by Maria D. Bernal, MD on March 15, 2026.


Introduction

A penetrating keratoplasty (PKP) is a surgical procedure involving a full thickness corneal transplant to restore vision or globe integrity[1]. The patient's diseased cornea is removed and replaced with a healthy, donor button.

Indications

  • Keratoconus and ectasias
  • Corneal degenerations
  • Corneal dystrophies
  • Noninfectious ulcerative keratitis
  • Microbial keratits including Fungal and Bacterial keratitis
  • Viral keratitis
  • Scarring after infectious keratitis
  • Congenital opacities
  • Chemical injuries
  • Mechanical trauma
  • Refractive indications
  • Regraft related to allograft rejection
  • Regraft unrelated to allograft rejection

History

Concepts of penetrating keratoplasty were first mentioned by Erasmus Darwin in 1760 as a corneal trephination for leucomatous cornea[2]. In the early 19th century, Karl Himley began experiments in corneal transplantation between animals. However, Himley’s student, Franz Reisinger, was the first to propose that a scarred human cornea could be replaced with a transparent animal cornea, which he termed a keratoplasty in 1824[2][3][4]. Early experiments in this concept were failures until 1837, when surgeon Samuel Bigger reported the first successful penetrating allograft done on a gazelle.  

Soon after Bigger’s report, Richard Kissam performed the first therapeutic xenograft on a human in 1838. Using a donor pig’s cornea, Kissam briefly increased the patient’s light perception, but the cornea opacified and was absorbed within 1 month postoperatively. Kissam continued on to write guidelines and principles for keratoplasty in 1844, which resemble techniques used today, such as fitting donor and recipient size, minimizing damage to the tissue, and protecting intraocular contents.

In 1905, Dr. Eduard Zirm performed the first successful human corneal transplant in Olmuntz. The patient Alois Golgar, who suffered from bilateral blindness, received a donor cornea from 11-year-old Karl Braur, who was blinded by a penetrating injury. The cornea was anucleated and split into two separate grafts. The right transplant failed and was removed, but the left cornea improved the patient’s visual acuity to 6/36. Other early keratoplasties were performed by André Magitot and Anton Elsching, in which most transplants were small at approximately 4.0 mm and followed similar techniques to Zirm. In 1914, Elsching developed the partial penetrating keratoplasty via the von Hippel trephine. Overall, early transplants had low success rates, which could also be attributed to early surgical techniques, such as a lack of steroids and antibiotics[3][5][6].

In the mid-1930s, transplantation success rates were increasing, but there were insufficient donors to meet demand for the procedure. Vladimir Filatov first suggested and popularized the use of cadaver corneas for transplantation, which had to be quickly enucleated and used within a short timeframe after death. This concept was further developed in 1944 by Richard Paton, establishing the first eye bank in the USA–the Eye Bank for Sight Restoration. In 1961, the Eye Bank Association of America was established, which reported approximately 2,000 transplants performed within its first year[5]. Since then, eye banks and corneal storage have improved drastically, allowing corneas to be stored for at least a week.

Ramon Castroviejo began studying graft techniques and developing new instruments for keratoplasty in the 1940s and 1950s, popularizing the practice in the USA. Castroviejo is known for utilizing a square corneal transplant and direct sutures, which were standardized until more efficient suturing materials and techniques were available[5]. Corneal graft rejection, first described by Eduard Maumanee, was and still is a significant barrier to graft survival. Development of cyclosporine A and corticosteroids in the 1950s began to improve outcomes of graft procedures, and the understanding of corneal graft rejection increased with figures such as Ali Asghar Khodadoust, for whom the Khodadoust line for corneal endothelial rejection is named[6].

New trephines have been introduced, such as the Hessburg-Baron trephine for oversized donor grafts, and the Hanna trephine for same-sized buttons. Additionally, the use of excimer lasers began in the 1990s after the work of Naumann et al[6].

Lamellar keratoplasty has recently resurged as an alternative graft procedure. Anterior and posterior lamellar keratoplasty has the advantage of only replacing the diseased cornea, preventing damage to healthy layers[4][6]. However, the procedure can be limited by donor and host cornea interface[4]. Shortage of donor corneas and risks of infection and rejection have prompted the development of artificial and bioengineered corneas. Pioneered by Strampelli in the 1960s, the osteo-odonto-keratoprosthesis uses a patient’s canine tooth as support for the lens[7]. Recombinant human collagen has been modeled into a biosynthetic cornea by Fagerholm et al, which provided worse results compared to human donors, but still was effective in vision improvement[6][8].

Preoperative Considerations

Prior to surgery, patients should be informed about expected visual outcomes, possible complications, and the postoperative course. Specific patient risk factors that may reduce the likelihood of graft success should be discussed and treated before surgery. Such risk factors include herpetic keratitis, glaucoma and intraocular inflammation[1].

Anesthesia Considerations

The choice of type of anesthesia for a penetrating keratoplasty depends on patient-specific factors and the surgeon's comfort levels. If a patient expresses anxiety and is likely to move around during the surgery, the surgeon may seriously consider general anesthesia. Notably, studies have shown that general anesthesia can significantly reduce the risk of intraoperative suprachoroidal hemorrhage. Alternatively, some ophthalmic centers routinely perform all penetrating keratoplasties with MAC and a peri- or retrobulbar block. In these cases, it is crucial to perform adequate ocular massage after the block to minimize posterior pressure. Furthermore, the surgical team may consider additional measures to minimize posterior pressure such as a reverse Trendelenburg position or IV mannitol. Pediatric cases are typically always performed under general anesthesia.

Anesthesia

General anesthesia with intubation should be considered, especially in younger patients. Retrobulbal anesthesia can also be used. Blood pressure should be kept as low as possible during the procedure, and acetazolamide and mannitol may be considered to decrease vitreous pressure. The pupil is typically constricted with pilocarpine for protection in phakic eyes.

Positioning of patient

To prevent poor centration, the head should be carefully positioned at 90 degrees to the body to prevent vertical and horizontal misalignment.

Surgical Procedure

Before initiating the surgery, the surgeon should decide on the appropriate size of the corneal trephine and donor punch. Typically, a trephine is selected to encompass the entirety of the corneal pathology (e.g. in cases of microbial infections). Sometimes in the case of microbial keratitis, the infection extends beyond the limbus. In these cases, the surgeon may choose to perform a larger corneoscleral graft. In other extensive cases, such as with corneal dystrophies, corneal trephination may not include the entirety of the pathology. In these cases, a smaller graft can be used as long as it allows for the visual axis to be clear. The use a corneal button 0.25-0.50mm larger than the diameter of the host corneal opening is recommended as it can help reduce excessive postoperative corneal flattening, reduce the risk of secondary glaucoma, and enhance wound closure. In cases of keratoconus, some surgeons will opt to use a corneal button the same size as the host corneal trephination, in anticipation of potential future graft steepening.

After selecting the sizes of the trephine and punch, the following steps are performed:

  1. The initial step in penetrating keratoplasty should be the preparation and punch of the donor tissue. The epithelial side of the donor may be marked as well to guide suture placement. It is critical to prepare the donor tissue prior to entering the patient's eye, to be prepared for any need for urgent closure.
  2. The host cornea is entered with a paracentesis blade and the anterior chamber is filled with viscoelastic. Of note, some surgeons will fill the anterior chamber with viscoelastic after trephining the host cornea, without the need for a paracentesis.
  3. The surgeon may choose to mark the host cornea with an RK marker, and the host cornea is trephined.
  4. The donor tissue is placed endothelial side down on the recipient's eye.
  5. The cornea is then sutured in place with either interrupted or continuous sutures. Interrupted sutures are preferred in vascularized, inflamed, or thinned corneas as well as in pediatric cases. Typically 16 sutures are placed, although in large corneal grafts or corneoscleral grafts, additional sutures may be necessary. Suture placement is usually performed to minimize the development of astigmatism, with every other suture being placed 180 degrees away from the previous suture. The first four cardinal sutures are placed at the 12:00, 3:00, 6:00, and 9:00 positions. Care must be taken so that each suture has equal tension compared to the other sutures.
  6. Prior to placement of the final 2 sutures, the viscoelastic is removed from the anterior chamber. Typically, balanced salt solution is injected at one opening in the graft host junction, with an additional cannula placed at the opposite graft host junction 180 degrees away to allow the viscoelastic to "burp" out of the anterior chamber.
  7. All sutures are rotated so that the knots are buried.
  8. Some surgeons may choose to use a fluorescein strip to assess for leakage at the graft host junction.
  9. Subconjunctival steroid and antibiotic are injected, the eye is patched, and a shield is placed.


Video showing penetrating keratoplasty procedure[9]

https://vimeo.com/154371744?fl=pl&fe=sh

Combined Procedures

Penetrating keratoplasty may be combined with cataract surgery, secondary intraocular lens implantation, glaucoma surgery, and retinal surgery. In cases of combined retinal surgery, often a temporary keratoprosthesis is sutured in place first to allow for the retina surgeon to visualize the posterior segment. After completion of the retinal surgery, the temporary keratoprosthesis is replaced with the permanent corneal graft.

Postoperative Management

Postoperative management addresses concerns of graft rejection, infection and increased intraocular pressure. Topical steroid drops should be started postoperative to prevent inflammation and lower the risk of rejection. There is considerable variation in protocols for steroid use post PKP with no consensus regarding dosing, duration, and taper. Shimmura-Tomita et al found that PKP patients that stayed on topical steroid drops after a year had less risk of rejection and recommend ongoing low dose steroid drops[10]. In addition to steroid drops, prophylactic antibiotic drops should be given 4 to 6 x a day for at least the first two weeks following PKP. Anti glaucoma medications should be used to reduce high intraocular pressures and preservative free lubricating drops can be applied to prevent suture irritation[11].

Intraoperative Complications

  • Poor graft centration
  • Irregular trephination
  • Damage to the lens
  • Damage to the donor tissue
  • Choroidal hemorrhage and effusion
  • Incarceration of iris tissue in the wound
  • Vitreous in the anterior chamber
  • Positive Vitreous Pressure
    • PVP is the result of an increase in the vitreous cavity pressure as the volume decreases due to external compression or acute intraocular intumescence. Acute and prolonged hypotony can lead to vessel rupture and significant complications such as suprachoroidal hemorrhage[12]. Risk for PVP is increased in patients with ocular disorders such as iris pathology, previous ocular trauma, zonulopathy, a shallow anterior chamber, and acute angle-closure glaucoma[12].
      For management, refer to Managing Positive Vitreous Pressure in Penetrating Keratoplasty: Techniques and Challenges

Postoperative Complications

  • Wound leak
    • Wound leak is associated with premature suture removal, abnormal wound healing, acute increase in intraocular pressure, edema, and trauma. Wound leak typically occurs within the first 18 months postoperatively, but cases of late occurrence 10 years later and beyond have been reported[13].
      Early detection and closure of the wound is essential to preserve visual acuity and prevent severe damage. Patients should minimize contact sports and wear protective eyewear when needed to reduce the risk of trauma[13].
  • Glaucoma
  • Endopthalmitis
  • Primary endothelial failure
    • Primary endothelial failure is indicated by diffuse edema that fails to clear after the immediate postoperative period, which clouds the donor cornea and results in loss of transparency and vision. Risk factors include smaller graft size, increased intraocular pressure, and recipient glaucoma or previous glaucoma surgery[14].
      Endothelial failure accounts for the majority of indications for regrafting, and options for management include repeat penetrating keratoplasty, Descemet stripping (DSAEK/DSEK), or Descemet membrane endothelial keratoplasty (DMEK). These secondary repeat grafts typically will have a higher risk for failure and/or rejection compared to the initial keratoplasty. Overall, repeat penetrating keratoplasty has a lower failure rate within the first 12 months compared to Descemet procedures; 2-year survival rates for DMEK are higher compared to repeat PKP and DSAEK[15]. Survival rates beyond this period present mixed results between studies. DSAEK/DSEK has the advantage of faster recovery and avoids the risk for suture-induced astigmatism. However, repeat PKP does not require postoperative posturing and should be considered in cases of stromal opacity, complex anatomy, or prior astigmatism[15].
  • Persistent epithelial defect
    • Persistent epithelial defects (PED) arise from the cornea failing to re-epithelialize and heal within two weeks of insult or operation, and increase the risk for infection, angiogenesis, vision loss, scarring, melting, and perforation.
      Treatment preservative-free artificial tears and ocular ointments for lubrication. Punctal plugs and bandage soft contact lenses can also be used for healing and preventing epithelial erosion. Tetracyclines may also be considered, and debridement and tarsorrhaphy can be used to reduce cornea exposure. If PED remains refractory, amniotic membrane grafting, autologous serum drops, and scleral contact lenses can be considered[16]. Newer therapies to consider include thymosinβ4 and hexagon to promote wound healing and decrease defect size[16][17].
  • Microbial keratitis
  • Late failure
    • Late endothelial failure (LEF) is characterized by an unexplained gradual decompensation of a previously stable and clear graft. Donor tissue with lower endothelial cell densities early endothelial cell loss increases the risk for LEF[14].
  • Recurrence of primary disease
    • Herpes Simplex Keratitis
      • Post-operative prophylaxis with antivirals is recommended to prevent recurrence of herpes simplex keratitis after graft, which increases the risk for complications and rejection. The American Academy of Ophthalmology recommends using high-dose acyclovir (800 mg 3x/day for at least 1 year) as prophylaxis after keratoplasty[18]. Goldblum et al demonstrated that high-dose oral acyclovir (800 mg 3-5x/day) with a gradual tapering over 3 years may also be effective. A review by Nardella et al also provides evidence for successful outcomes with high-dose systemic and oral antivirals and corticosteroids, with tapering for two-piece mushroom keratoplasty. However, it’s important to consider the risk for selection of acyclovir-resistant (ACVR) HSV-1: while rare, it should be weighed against the benefits of long-term therapy for the patient[19].
  • Astigmatism
    • Approximately 1 in 5 patients who undergo this procedure may develop post-operative astigmatism. This complication may arise from improper trephination size and location, donor graft sizing and disparity from recipient, corneal thickness, or suture placement. Post-operative medications are also possible factors[20].
      Mild degrees of astigmatism can be conservatively corrected via lenses or glasses, and inflammation and vascularization should be reduced before taking further measures for correction. Possible surgical interventions include suture adjustment, limbal relaxing incisions, excimer laser, intrastromal corneal ring segments, and intraocular lens-based procedures. In cases where other interventions are ineffective, repeat corneal transplantation may be needed.   Suture adjustment can be considered if astigmatism is adjusted immediately post-operative. For patients with interrupted sutures, sutures can be selectively removed for those contributing to the astigmatism. Continuous sutures are significantly more difficult to adjust via removal, but it is possible to rotate the sutures to loosen and tighten improper sutures. Further surgical interventions should be delayed until 3 to 4 months after suture removal. Relaxing incisions can be made to flatten the corneal meridian. The incision may be done manually with a diamond knife or via femtosecond laser-assisted arcuate keratotomy (FSAK). FSAK is associated with a lower risk of adverse effects such as wound dehiscence, infection, and perforation[20].   Topography-guided PRK or LASIK is effective for correcting astigmatism by mapping the corneal surface and guiding an excimer laser to reshape the cornea. However, some studies have shown that these procedures may not be effective long-term, and also report instances of graft rejection and corneal haze[20]. Toric intraocular lenses involve minimal manipulation of the cornea to maintain corneal integrity, thus are very predictable in their effect on astigmatism. However, IOLs are contraindicated in patients with posterior segment pathology, zonular instability, and irregular astigmatism[21].
  • Graft rejection (see below)

Corneal Graft Rejection

Rejection Risk factors

Various factors should be considered for a high risk of corneal graft rejection, including eyes with 2+ quadrants of vascularization, trephination over 8.25 mm, Herpes simplex keratitis, silicone oil keratopathy, previously failed grafts, infection and inflammation, and younger age.

Risk level can be categorized as level 1 (low), 2 (medium), 3 (high), and 4 (very high).

Low-risk: A first-time graft with a clear (no glaucoma), non-vascularized, and non-inflamed cornea.

Medium risk: A history of a prior graft, up to two quadrants of deep vascularization, previous but inactive herpes simplex keratitis, and mild inflammation.

High-risk: Two or more prior grafts, three to four quadrants of vascularization, active herpes keratitis, and active ocular inflammation. High-risk conditions also include a history of ocular surface disease.

Very High-risk: Two or more prior grafts with other risk factors, diffuse and deep vascularization, active herpes keratitis with ulcers or perforation, and severe trauma, such as chemical burns and Stevens-Johnson syndrome, accompanied by persistent inflammation[22].

  • Neovascularization
    • Graft failure increase is associated with the number of corneal quadrants that have neovascularizations, which lead to a loss of angiogenic privilege in the eye[23] . Vascularization is associated with chemical burns, trauma, leukomas, and dystrophies[23]. The use of antiangiogenic pharmaceuticals such as Bevacizumab may be effective in improving the survival of neovascularized corneas if used pre-PKP[23].
  • Repeated keratoplasties
    • Multiple keratoplasties demonstrate a poorer prognosis and survival for subsequent keratoplasties. Survival decreases incrementally with successive transplants: 40% following an initial transplant, 68% after a second transplant, and 80% upon a third transplant[22]. This is possibly explained by deterioration of the corneal bed, increased intraocular pressure from previous procedures, and breakage of immunologic privilege in the anterior chamber[23].
  • Herpes Simplex Keratitis
    • HSK may predispose the eye to corneal neovascularization and recurrence of the disease in the graft[23]. Prophylactic antivirals reduce the risk for recurrent HSK after graft transplant, but still carry a higher risk for graft failure[22].
  • Inflammation
    • Pre-existing chemical burns, trauma, perforation, uveitis, and other inflammatory diseases of the eye pose a higher risk for graft rejection. Performing PKP during ongoing inflammation, commonly referred to as “hot grafting,” increases the risk for immune reaction. This is primarily due to the disruption of inflammatory and anti-inflammatory factors, leading to abnormal stimulation of immune cells[22].
  • Donor Age and sex
    • Association with donor age and successful keratoplasty are not well defined and vary between studies, but older donors (70+) may have a slightly higher risk for failure[23][24]. Pediatric patients also carry a higher risk of rejection due to a heightened immune response[22]. Grafts from donor males may have a minimally lower chance of survival, but are not statistically significant[23].
  • Graft size
    • Performing a larger diameter PKP may be associated with higher rates of rejection due to increased exposure of antigens to limbic vasculature[22]. Barraquer et al found statistically significant differences between graft size and rejection in univariate analysis, but other literature provides mixed results on this association[23].

Symptoms

  • Decreased vision, pain, redness and photophobia after a corneal transplant

Signs

  • Keratic precipitates or a white line on the corneal endothelium (Khodadoust line)
  • Stromal edema or infiltrates
  • Subepithelial or epithelial edema
  • Conjunctival injection
  • Anterior chamber cells or flare
  • Neovascularization

Differential Diagnosis

  • Noncompliance with steroid drops
  • Increased intraocular pressure
  • Uveitis
  • Suture abscess
  • Corneal infection
  • Recurrent disease in the graft (e.g. herpetic or corneal dystrophy)

Treatment

  • Start a topical steroid, such as prednisolone acetate 1%, every 1 to 2 hours immediately. Use a cycloplegic agent. Systemic steroids (prednisone 40-80 mg daily) should be considered in cases that do not respond to topical steroids and in recurrent rejection episodes. [25]

Prevention of PKP/corneal graft rejection

Pre-operative

Pre-operative considerations should aim to control ocular surface inflammation and vascularization to minimize the risk of graft rejection. Corticosteroids before the procedure can help decrease the resulting ocular inflammation. Immunomodulators such as cyclosporine A or tacrolimus should be considered if the patient has vernal or atopic keratoconjunctivitis[22]. If inflammation is already present, the transplant should be postponed until it is well-controlled for at least six months[22]. Corticosteroids and immunomodulators should also be used post-operation for immunosuppression.

To reduce corneal vascularization, therapy targeting the VEGF family may be utilized. Corneal neovascularization is primarily driven by VEGF-A, which promotes angiogenesis. Bevacizumab is a recombinant, human monoclonal antibody against VEGF-A that can be used preoperatively or postoperatively: it inhibits endothelial cell proliferation, differentiation, and migration[22]. Bevacizumab may be administered topically or subconjunctival/corneal intrastromal. Topical administration reduces neovascularization to a greater degree, but subconjunctival administration leads to higher intraocular concentrations and slower release. Co-administration at both sites may improve graft survival in high-risk patients, but should be monitored carefully as complications, including corneal melt and wound dehiscence, may occur[22].

Ranimizumab is a humanized Fab antibody against all VEGF-A isoforms, which has deeper penetration into corneal tissue than bevacizumab and may have a stronger anti-neovascularization effect. However, studies have not been conclusive between the two[26].

Laser-induced coagulation with argon or 577 nm laser can be used for the treatment and prevention of neovascularization via obliterating abnormal vessels. Fine needle diathermy (FND) is another procedure that has shown efficacy in reducing vascularization in initial studies: FND utilizes a coagulating current to occlude afferent and efferent vessels. However, re-treatment is often necessary, and the process of destroying vessels can activate inflammatory mediators and VEGF. Thus, combination therapy with bevacizumab has been utilized to increase graft-survival[22].

A possible alternative approach is through corneal cross-linking (CXL), which cross-links collagen fibers together to strengthen the cornea and prevent vascularization. Schaub et al suggests that treatment with CXL before PKP reduces corneal neovascularization and reduces pathologic immune reactions[27].  

Intra-operative

Prolonging storage of donor corneas can deplete antigen-presenting cells, reducing immunogenicity of the donor tissue. However, long storage times can also damage the endothelial cells, which are important for full-thickness keratoplasty. The use of glycerol-cryopreserved corneal tissue, which eliminates antigen-presenting cells, in deep anterior lamellar keratoplasty has been shown to reduce risk for rejection and improve graft survival compared to fresh corneal tissue[28]. Depleting CD45+ immune cells via antibodies to donor tissue can also increase cell depletion speed, reducing preparation time[22][29]--however, this approach does not affect antigen-presenting cells in the recipient, thus may be less effective in high-risk patients who have a high immunogenic load due to inflammation or vascularization.

In cases of significant neovascularization and scarring, mushroom-type keratoplasty may be an option if the patient's endothelium is healthy. The procedure creates a graft with a large anterior and small posterior lamella, resulting in minimal recipient endothelial removal, thereby reducing risk for rejection[22][30].

Post-operative

Post-operative management should aim to prevent, diagnose, and treat graft rejections as early as possible. It’s important to educate the patients on the early signs and symptoms of possible graft rejection.

  • Corticosteroids and Immunosuppression
    • Topical prednisolone acetate 1 % and dexamethasone sodium phosphate 0.1% eye drops are a first-line treatment for immunosuppression after keratoplasty. High-risk patients should receive more frequent and intensive regimens, such as every 2-4h with a gradual tapering over 6-12 months. If conventional treatment is refractory, one can consider intravitreal dexamethasone implants[22]. Oral corticosteroids should be considered in high-risk patients, especially in those with system inflammatory conditions. Oral prednisone, 1 mg/kg per day, can be administered perioperatively and tapered over 4-8 weeks after keratoplasty[22].  Intravenous methylprednisolone sodium may be considered for high-risk patients as well. However, prolonged use of corticosteroids carries risks for adverse events such as impaired wound healing, cataracts, glaucomas, and infectious keratitis, as well as many systemic side effects. Thus, alternative immunosuppressive therapies should also be considered for long-term treatment. Cyclosporine A, a macrolide, is a calcineurin inhibitor that selectively inhibits T lymphocyte activation. Treatment for keratoplasty ranges from 0.5-2.0% for eye drops, as well as systemic administration of 3-4 mg/kg per day[22]. The efficacy of cyclosporine A is controversial for corneal graft rejection and survival. Multiple clinical trials found no significant difference between cyclosporine A-treated patients and controls22. However, a cyclosporine A drug-delivery system placed in the anterior chamber has been shown to increase graft survival and may be an effective prophylaxis with minimal toxicity to the cornea and iris[22]. Another study in a drug-delivery system showed reduced immunocyte density and IL-2, as well as increased graft survival time in rabbits[26]. Side effects include discomfort and a burning sensation at the site of application. Systemic administration can lead to adverse effects such as hypertension, nephrotoxicity, endocrine and metabolic changes, neurotoxicity, and reactivation of herpes simplex keratitis. Tacrolimus, a macrolide, is a significantly more potent calcineurin inhibitor compared to cyclosporine A. Topical tacrolimus is available in eye drops at 0.03% and 0.1% and ointment at 0.1%. Tacrolimus may be administered 2-4 times daily for 18-24 months, though the optimal length has not been determined[22][31]. A meta-analysis by Al Khathami et al suggests that tacrolimus is an effective treatment for the prevention of graft rejection and improved survival, especially in high-risk patients and when used in conjunction with corticosteroids[32]. Side effects for tacrolimus are significant and may lead to discontinuation in many patients, including paresthesia, tremors, fatigue, reversible nephrotoxicity, diabetes, hypertension, malaise, and GI disturbance[22]. Mycophenolate mofetil (MMF) is a prodrug that is converted to mycophenolic acid and can be used to effectively decrease the risk of rejection and graft survival. MMF possesses synergistic effects with acyclovir, and thus may be especially useful for post-operative treatment of transplant for herpetic keratitis. MMF is generally well-tolerated, with the most common side effects being anemia, leukopenia, hypertension, diarrhea and other GI disturbances, nausea, hyperlipidemia, and arthralgia[22].

Additional Resources

References

  1. ↑ 1.0 1.1 Patel, S.V., & McLaren, J.W. (2023). Penetrating keratoplasty. In M. Yanoff & J.S. Duker (Eds), Ophthalmology (6th ed., Chapter 4.28). Elsevier.
  2. ↑ 2.0 2.1 Amer MR, Elzembely AI. Evolution of penetrating keratoplasty: the three eras, a brief historical review. Adv Ophthalmol Vis Syst. 2023;13(3):86-88. DOI: 10.15406/aovs.2023.13.00447
  3. ↑ 3.0 3.1 Sathyan, Sanitha. When the eye “met” the eye: A peek into the history of corneal transplantation. Kerala Journal of Ophthalmology 36(1):p 57-58, Jan–Apr 2024. | DOI: 10.4103/kjo.kjo_28_24
  4. ↑ 4.0 4.1 4.2 Crawford AZ, Patel DV, McGhee CNj. A brief history of corneal transplantation: From ancient to modern. Oman J Ophthalmol. 2013;6(Suppl 1):S12-S17. doi:10.4103/0974-620X.122289
  5. ↑ 5.0 5.1 5.2 Güell JL, El Husseiny MA, Manero F, Gris O, Elies D. Historical Review and Update of Surgical Treatment for Corneal Endothelial Diseases. Ophthalmol Ther. 2014;3(1-2):1-15. doi:10.1007/s40123-014-0022-y
  6. ↑ 6.0 6.1 6.2 6.3 6.4 Moffatt, S.L., Cartwright, V.A. and Stumpf, T.H. (2005), Centennial review of corneal transplantation. Clinical & Experimental Ophthalmology, 33: 642-657. https://doi.org/10.1111/j.1442-9071.2005.01134.x
  7. ↑ Sepehr Feizi, Firouze Hatami, Sina Khosravi Mirzaei, Kia Bayat, Medical and surgical approaches to prevent corneal graft rejection in high-risk recipients, Survey of Ophthalmology, 2025, ISSN 0039-6257, https://doi.org/10.1016/j.survophthal.2025.09.024.
  8. ↑ Per Fagerholm et al., A Biosynthetic Alternative to Human Donor Tissue for Inducing Corneal Regeneration: 24-Month Follow-Up of a Phase 1 Clinical Study.Sci. Transl. Med.2,46ra61-46ra61(2010).DOI:10.1126/scitranslmed.3001022
  9. ↑ Donaghy CL, Vislisel JM, Greiner MA. An Introduction to Corneal Transplantation. May 21, 2015; Available from: https://eyerounds.org/tutorials/cornea-transplant-intro/
  10. ↑ Shimmura-Tomita M, Shimmura S, Satake Y, Shimazaki-Den S, Omoto M, Tsubota K, Shimazaki J. Keratoplasty postoperative treatment update. Cornea. 2013 Nov;32 Suppl 1:S60-4. doi: 10.1097/ICO.0b013e3182a2c937. PMID: 24104936.
  11. ↑ Gurnani, B., & Kaur, K. (2023). Penetrating keratoplasty https://www.ncbi.nlm.nih.gov/books/NBK592388
  12. ↑ 12.0 12.1 Alkharashi, M., AlAbdulhadi, H. A., Otaif, W., Alahmadi, A. S., Alanazi, B., Al Habash, A., … Bin Helayel, H. (2023). Incidence, Pathophysiology, Complications, and Management of Positive Vitreous Pressure During Penetrating Keratoplasty: A Literature Review. Clinical Ophthalmology, 17, 583–590. https://doi.org/10.2147/OPTH.S382502
  13. ↑ 13.0 13.1 Pettinelli DJ, Starr CE, Stark WJ. Late Traumatic Corneal Wound Dehiscence After Penetrating Keratoplasty. Arch Ophthalmol. 2005;123(6):853–856. doi:10.1001/archopht.123.6.853
  14. ↑ 14.0 14.1 Patel SV, Diehl NN, Hodge DO, Bourne WM. Donor Risk Factors for Graft Failure in a 20-Year Study of Penetrating Keratoplasty. Arch Ophthalmol. 2010;128(4):418–425. doi:10.1001/archophthalmol.2010.27
  15. ↑ 15.0 15.1 Roberts, H.W., de Benito-Llopis, L. Comparison of repeat penetrating keratoplasty, DSAEK and DMEK for the management of endothelial failure of previous PK. Eye 37, 3596–3601 (2023). https://doi.org/10.1038/s41433-023-02561-5
  16. ↑ 16.0 16.1 American Academy of Ophthalmology. (2016, April 28). Healing a persistent corneal epithelial defect. American Academy of Ophthalmology. https://www.aao.org/eyenet/article/healing-persistent-corneal-epithelial-defect
  17. ↑ Golhait P, Peseyie R. Persistent Epithelial Defect. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK573060/
  18. ↑ Bhatt UK, Abdul Karim MN, Prydal JI, Maharajan SV, Fares U. Oral antivirals for preventing recurrent herpes simplex keratitis in people with corneal grafts. Cochrane Database Syst Rev. 2016 Nov 30;11(11):CD007824. doi: 10.1002/14651858.CD007824.pub2. PMID: 27902849; PMCID: PMC6464863.
  19. ↑ Nardella M, Yu AC, Busin M, Rizzo R, Zauli G. Outcomes of Corneal Transplantation for Herpetic Keratitis: A Narrative Review. Viruses. 2024; 16(9):1403. https://doi.org/10.3390/v16091403
  20. ↑ 20.0 20.1 20.2 Bhayani R, Walkden A. Managing Post Keratoplasty Astigmatism. Clin Ophthalmol. 2024;18:1727-1734. Published 2024 Jun 13. doi:10.2147/OPTH.S393975
  21. ↑ Mohankumar A, Mohan S. Toric Intraocular Lenses. [Updated 2023 Jul 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK592396/
  22. ↑ 22.00 22.01 22.02 22.03 22.04 22.05 22.06 22.07 22.08 22.09 22.10 22.11 22.12 22.13 22.14 22.15 22.16 22.17 22.18 22.19 Sepehr Feizi, Firouze Hatami, Sina Khosravi Mirzaei, Kia Bayat, Medical and surgical approaches to prevent corneal graft rejection in high-risk recipients, Survey of Ophthalmology, 2025, ISSN 0039-6257, https://doi.org/10.1016/j.survophthal.2025.09.024.
  23. ↑ 23.0 23.1 23.2 23.3 23.4 23.5 23.6 23.7 Barraquer RI, Pareja-Aricò L, Gómez-Benlloch A, Michael R. Risk factors for graft failure after penetrating keratoplasty. Medicine (Baltimore). 2019;98(17):e15274. doi:10.1097/MD.0000000000015274
  24. ↑ Mandal S, Maharana PK, Kaweri L, Asif MI, Nagpal R, Sharma N. Management and prevention of corneal graft rejection. Indian J Ophthalmol. 2023;71(9):3149-3159. doi:10.4103/IJO.IJO_228_23
  25. ↑ The Wills Eye Manual, 4th Edition. Kunimoto, Kanitkar, & Makar. Lippincott, 2004.
  26. ↑ 26.0 26.1 Merz, P.R., Röckel, N., Ballikaya, S. et al. Effects of ranibizumab (Lucentis®) and bevacizumab (Avastin®) on human corneal endothelial cells. BMC Ophthalmol 18, 316 (2018). https://doi.org/10.1186/s12886-018-0978-9
  27. ↑ Schaub, Friederike MD*; Hou, Yanhong MD, PhD*,†,‡; Zhang, Wei MD*; Bock, Felix PhD*; Hos, Deniz MD, PhD*,§; Cursiefen, Claus MD, PhD*,§. Corneal Crosslinking to Regress Pathologic Corneal Neovascularization Before High-Risk Keratoplasty. Cornea 40(2):p 147-155, February 2021. | DOI: 10.1097/ICO.0000000000002406
  28. ↑ Li J, Yu L, Deng Z, et al. Deep anterior lamellar keratoplasty using acellular corneal tissue for prevention of allograft rejection in high-risk corneas. Am J Ophthalmol. 2011;152(5):762-70.e3. doi:10.1016/j.ajo.2011.05.002
  29. ↑ Xian Zhang, Linling Shen, Yiping Jin, Daniel R. Saban, Sunil K. Chauhan, Reza Dana; Depletion of Passenger Leukocytes from Corneal Grafts: An Effective Means of Promoting Transplant Survival?. Invest. Ophthalmol. Vis. Sci. 2009;50(7):3137-3144. https://doi.org/10.1167/iovs.08-1899.
  30. ↑ Scorcia V, Busin M. Survival of mushroom keratoplasty performed in corneas with postinfectious vascularized scars. Am J Ophthalmol. 2012;153(1):44-50.e1. doi:10.1016/j.ajo.2011.05.020
  31. ↑ Azevedo Magalhaes O, Shalaby Bardan A, Zarei-Ghanavati M, Liu C. Literature review and suggested protocol for prevention and treatment of corneal graft rejection. Eye (Lond). 2020;34(3):442-450. doi:10.1038/s41433-019-0517-9
  32. ↑ Nardella M, Yu AC, Busin M, Rizzo R, Zauli G. Outcomes of Corneal Transplantation for Herpetic Keratitis: A Narrative Review. Viruses. 2024; 16(9):1403. https://doi.org/10.3390/v16091403
  1. H.E., Barron, L., McDonald, M.B., eds., The Cornea, 2d ed., 1996
  2. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 8. External Disease and Cornea. San Francisco: American Academy of Ophthalmology; 2023-2024: 472-485.
Retrieved from "https://eyewiki.org/w/index.php?title=Penetrating_Keratoplasty&oldid=127218"
The Academy uses cookies to analyze performance and provide relevant personalized content to users of our website.
Learn more
Powered by MediaWiki
Powered by Canasta
Powered by Semantic MediaWiki