EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: We analyzed prevalence, ocular risk factors, and medical/surgical management of eyes with de novo intraocular pressure elevation following penetrating keratoplasty.
Materials and Methods: In this retrospective study, we assessed 400 patients who underwent penetrating keratoplasty from January 2018 to August 2024 for de novo intraocular pressure elevation during the postoperative follow-up period. We evaluated patient demographics, ocular risk factors, indications for penetrating keratoplasty, topical steroid use, peak and regulated intraocular pressure, need for antiglauco-matous medication/surgery, and mean follow-up time.
Results: After exclusion of eyes with preexisting glaucoma, 55 of 400 patients (13.7%) showed intraocular pressure elevation. Postoperatively, mean peak intraocular pressure was 31.92 ± 6.24 mm Hg. To achieve intraocular pressure control, an average of 2.12 ± 0.84 topical antiglaucoma medications were administered. Eleven patients (20%) required surgical intervention. Eyes with peripheral anterior synechiae had an increased risk of the need for antiglauc-omatous surgery (P = .03; odds ratio 0.175; 95% CI, 0.035-0.868). In addition, significantly higher prevalence of peripheral anterior synechiae was demonstrated among eyes with intraocular pressure elevation occurring within the first 24 weeks postoperatively (P = .03). Peak intraocular pressure levels were higher in aphakic eyes (P = .04; odds ratio 0.87; 95% CI, 0.77-0.99). Furthermore, the peak (P = .02; odds ratio 0.85; 95% CI, 0.74-0.98) and regulated (P = .02; odds ratio 0.7; 95% CI, 0.51-0.95) intraocular pressures in the postoperative period were significantly higher in eyes that had undergone tectonic penetrating keratoplasty.
Conclusions: Eyes with preexisting peripheral anterior synechiae, aphakia and eyes undergoing penetrating keratoplasty for tectonic reasons are more vulnerable to postoperative intraocular pressure elevation/glaucoma. Early onset of intraocular pressure issues may be linked to preexisting inflammation and extended use of strong topical steroids, which highlights the importance of proactive care and effective management to prevent complications.

Key words : Aphakia, Glaucoma, Peripheral anterior synechiae, Tectonic keratoplasty

Penetrating keratoplasty (PK) has been used for many years to restore ocular integrity and vision, particularly in diseases that affect all layers of the cornea.¹ In recent times, PK has been superseded by lamellar corneal transplant due to a variety of reasons, including issues with sutures, the fact that PK is a full-thickness surgery, high graft rejection rates, astigmatism, the necessity of long-term topical steroid use, and the limited potential for visual improvement.² Nevertheless, PK remains an effective option for the surgical treatment of many complex corneal pathologies.¹
Intraocular pressure elevation (IOP)/glaucoma after PK is one of the most serious complications that threaten graft survival, the optic disc, and ultimately vision.^1-4 The incidence of glaucoma following PK ranges between 10% and 53%, and numerous etiological factors have been documented.^1,4 The distortion of the trabecular meshwork consequent to the removal of the Descemet membrane, as well as the deformation of the anterior segment morphology, are the principal factors implicated in patients with high IOP/glaucoma following PK.^2,5 Furthermore, peripheral anterior synechiae (PAS), aphakia, previous PK, history of trauma, corneal perforation, and steroid response have been identified as risk factors for post-PK IOP elevation.^6-9 It is imperative to expeditiously implement IOP reduction treatments, given the complexity of these eyes and the risk of permanent optic disc damage that can result from prolonged IOP elevation following PK.^8,9
In this study, we aimed to evaluate demographic and clinical characteristics, the prevalence, potential ocular risk factors, and medical/surgical management of eyes with de novo IOP elevation following PK.

Materials and Methods

This study followed the tenets of the Declaration of Helsinki and was approved by the University of Health Sciences, Ankara Bilkent City Hospital Ethics Committee (IRB No. 1-24-242). The need for consent to participate was deemed unnecessary for retros-pective studies by the Ethics Committee. The data of 400 patients who underwent PK from January 2018 and August 2024 were retrospectively analyzed. Of these, 55 eyes of 55 patients with de novo IOP elevation in the postoperative follow-up period were included in this study. Patients who did not attend regular follow-up visits after surgery, whose follow-up period was less than 6 months, who did not comply with the treatment process, and who had preexisting glaucoma were excluded.
Post-PK IOP elevation was characterized by a persistent elevated IOP of ≥22 mm Hg, as determined by 2 consecutive visits, that has led to the initiation of an antiglaucomatous medication or surgical intervention.⁸ Post-PK assessments, including slit-lamp biomicroscopy, angle morphology assessment with indirect gonioscopy, IOP measurement with Goldmann applanation tonometry, best corrected visual acuity (BCVA), and fundoscopy were con-ducted at each visit. Optic disc and retinal nerve fiber layer analyses were performed with an ophthalmic imaging system with Swept Source technology (SS-OCT; DRI OCT Triton, Topcon) once every 6 months.
We evaluated patient demographics, ocular features (including the presence of PAS, pseudo-exfoliation (PSX), and host vascularization; history of previous vitrectomy, lens status, and multiple PK surgeries), indications for PK (keratoconus, corneal scarring, bullous keratopathy, and tectonic surgery), and type of topical steroid used. We also assessed the interval between PK and IOP elevation, use of antiglaucomatous medication, peak and regulated IOP, need for glaucoma surgery, BCVA levels (preoperatively and postoperatively), and mean follow-up time.
Eyes that exhibited iridotrabecular contact for a minimum of 2 clock hours were identified as having PAS. If vascularization presence in the limbus was greater than one-fourth of the cornea in the recipient bed, then this was considered to be host vascu-larization.
Surgical technique
All PK procedures were performed in patients under general anesthesia in a standardized manner by 1 of the 2 experienced corneal surgeons (OEK and EEK). The recipient bed diameter was determined based on the white-to-white corneal measurements (7.50 mm or 7.75 mm), and after marking the recipient cornea, the donor graft was prepared to be 0.5 mm larger than the host cornea. After full-thickness trephination, the recipient cornea was removed. The donor cornea was meticulously sutured to the recipient bed with 16 interrupted 10-0 nylon sutures. The surgery was concluded with subconjunctival antibiotic-corticosteroid injection.
Postoperative treatment regimen and follow-up
The postoperative treatment regimen consisted of topical moxifloxacin 0.5% (4 times daily), dexamethasone 0.1% (6 times daily), and artificial tear drops (4 times daily). Table 1 shows the standard topical steroid regimen after PK. In cases where IOP elevation develops, topical steroid dosage is tapered, and a weaker topical steroid (eg, loteprednol etabonate 0.5%) is substituted. However, in cases deemed to be at high risk with regard to graft failure and rejection (including multiple PK procedures, inflamed eyes, and vascularized grafts), topical treatment was continued with prednisolone acetate 1%. Antiglaucomatous treatment was initiated in cases where IOP exceeded 22 mm Hg on at least 2 visits. Surgical intervention is indicated in cases where IOP fails to decrease below 22 mm Hg despite the administration of maximum medical treatment. Patients were postoperatively observed at 1 day, 1 week, and 1 month, with follow-up interval then increased to every 2 months. After the first postoperative year, patients were followed up every 6 months.
Statistical analyses
We used SPSS software (version 22.0; IBM) for data analyses. In the descriptive analysis, we presented quantitative variables as mean values with SD or median values with IQR (25th-75th percentile) and categorical variables as frequencies and percentages.
We used the χ² test or the Fisher exact test to compare categorical variables. Furthermore, we used the t test to compare continuous variables with a normal distribution and the Mann-Whitney U test for variables lacking a normal distribution. We evaluated the association between continuous variables with the Spearman correlation coefficient. We used logistic regression model to assess the risk factors associated with IOP elevation following PK and to estimate the adjusted odds ratio (OR). P < .05 was considered statistically significant in all cases.

The mean age of patients was 54.04 ± 18.18 years, and mean follow-up time was 114.56 ± 78.04 weeks. Table 2 lists demographics and clinical and ocular features of patients. After cases with preexisting glaucoma were excluded, among 400 patients who underwent PK, 55 (13.7%) were shown to develop de novo IOP elevation. The mean time from PK to IOP elevation was 32.98 ± 5.70 weeks. Postoperatively, patients required a mean of 2.12 ± 0.84 topical antiglaucoma drugs for IOP control.
Surgical intervention was necessary in 11 patients (20%) due to persistent IOP elevation, including Ahmed glaucoma valve implantation (5 eyes), trabeculectomy (2 eyes), goniosynechialysis (2 eyes), and diode laser cyclophotocoagulation (2 eyes). Among these, 6 eyes had a history of vitrectomy, and 4 had PAS.
During follow-up, the mean peak IOP was 31.92 ± 6.24 mm Hg (IQR, 11 mm Hg), and the mean regulated IOP was 13.32 ± 3.81 mm Hg (IQR, 6 mm Hg). The mean interval from PK to glaucoma surgery was 35.3 weeks. PAS were detected in 8 patients (8/55, 14.5%) who developed post-PK IOP elevation. Among the remaining 345 patients, PAS was observed in 27 cases (7.8%). When patients were divided into early and late IOP elevation groups (with the 24th postoperative week as the cutoff), 33 eyes were found to have developed IOP elevation within 24 weeks, whereas 22 eyes developed IOP elevation thereafter.
Correlation analysis demonstrated a significantly higher prevalence of PAS among eyes with IOP elevation occurring within the first 24 weeks postoperatively (P = .03). The mean central corneal thickness at the last visit was 592.98 ± 73.5 μm. The postoperative levels of BCVA improved significantly versus preoperative levels (1.80 ± 0.69 to 1.16 ± 0.69 LogMAR P < .001). No patients had pupillary block in the postoperative period.
Logistic regression analysis identified PAS as a significant risk factor for requiring antiglaucomatous surgery (P = .03; OR 5.7; 95% CI, 1.1-28.3). In the postoperative period, the highest IOP values (P = .02; OR 0.85; 95% CI, 0.74-0.98) and regulated IOP values (P = .02; OR 0.7; 95% CI, 0.51-0.95) were significantly elevated in eyes that were treated with tectonic PK. Peak IOP levels were also higher in aphakic eyes (P = .04; OR 0.87; 95% CI, 0.77-0.99). A shorter interval between PK and IOP elevation was associated with older age, PAS, aphakia, and graft vascularization. However, these factors lost statistical significance in multivariate analysis. Table 3 lists relationships between ocular risk factors and IOP elevation, as well as medical and surgical management.

The present study provides data about the prevalence of IOP elevation in post-PK eyes in a Turkish population, alongside an investigation of the potential contributing factors. In contrast to findings of previous reports, our study excluded eyes with glaucoma and focused exclusively on eyes with de novo IOP elevation, thereby providing a different perspective on this subject. We found a higher frequency of antiglaucomatous surgery in patients with PAS and found that aphakic eyes had higher IOP values following PK. In addition, postoperatively, peak and regulated IOP values were higher in eyes treated with PK for tectonic causes.
The presence of IOP elevation/glaucoma after PK is a well-recognized complication of this surgery. As demonstrated in the extant literature, the incidence of IOP elevation/glaucoma ranged widely between 8.7% and 47% within the postoperative period.^7,8,10-14 However, cases with preexisting glaucoma are not excluded in most of those studies. On the other hand, Chanbour and colleagues reported an incidence of 34.9% in their study, which excluded patients with glaucoma. This relatively high rate was attributed to the presence of complex diseases and regrafts included in their study.¹³ In the present study, the prevalence of post-PK IOP elevation was found to be 13.7%, which is relatively low compared with previously published data, and this may also be related to the exclusion of cases with preexisting glaucoma. Table 4 presents a selection of studies that show IOP elevation rates after PK with the most prevalent risk factors.
In various studies, preexisting glaucoma, com-bined surgeries (PK with lens extraction), and lens status (pseudophakia and aphakia vs phakic eyes) have been identified as the most significant factors with regard to IOP elevation/glaucoma develop-ment following PK.^2,9 In the present study, we observed higher postoperative IOP levels in aphakic eyes. In aphakic eyes, structural alterations of the anterior chamber angle may occur, contributing to the ongoing microtraumatic stress on trabeculum due to PK.^2,15
In several studies, preexisting PAS has been identified as a risk factor for increased IOP in post-PK eyes.^8,11,16,17 We found a significantly greater need for glaucoma surgery following PK in eyes with PAS, consistent with those previously published studies. In addition, when patients were divided into 2 groups according to the timing of early versus late IOP elevation using the 24th postoperative week (when less potent steroids were initiated) as the cutoff point, we observed that the incidence of PAS was significantly higher in eyes with IOP elevation occurring within 24 weeks (P = .03). The development of PAS leads to impaired aqueous drainage through the obstruction of the trabecular meshwork, which can result in sustained elevation of IOP. It is also imperative to acknowledge that the PAS pattern may persist in its progression. Kusano and colleagues reported a significant correlation between elevated inflammatory cytokines in the aqueous humor and PAS formation leading to the subsequent development of glaucoma.¹⁷ It has also been established that PAS development can result in chronic inflammation within the anterior chamber, causing a vicious cycle.¹⁸ In particular, eyes in which PK has been the choice of surgery may have been previously exposed to intense inflammation (such as eyes with bullous keratopathy, previous keratitis, or ocular trauma), and PAS is likely to develop in these eyes.^19,20 Similarly, studies have demonstrated that eyes treated with PK for reasons associated with reduced inflammation, such as keratoconus, corneal scarring, or dystrophies, may exhibit diminished IOP elevation in the postoperative period.^11,12
In this study, we further determined that peak and regulated IOP levels were higher in the postoperative period in eyes treated with PK for tectonic reasons. Such cases frequently present with marked inflammation, due to melting of the cornea, the cause of which is often either infectious or autoimmune in nature.²¹ This inflammatory process may result in the formation of synechiae and fibrin membranes, which can potentially lead to angle damage. Furthermore, the presence of a shallow anterior chamber in perforated corneas can also contribute to the development of synechiae.^22-24 In the context of active and intense inflammation in these patients, there may be a requirement for more intensive anti-inflammatory treatment following PK. In our routine practice, the transition to topical loteprednol etabonate occurs at the 6-month mark. However, in cases involving the risk of inflammation that can lead to graft rejection and failure, a longer course of prednisolone is the choice. Both the use of PK treatment for an eye with active inflammation and the prolonged use of prednisolone, which is known to be more potent in terms of IOP elevation,²⁵ may have led to earlier development of IOP elevation in these eyes.
Despite the presence of a significant number of cases with a history of combined surgery, vitrectomy, or trauma in the present study, these factors were not found to be associated with de novo post-PK IOP elevation in multivariate regression analyses, in contrast to the findings of various previously published studies.^7,9-11
In the present study, 20% of eyes that developed post-PK IOP elevation required surgical intervention, most commonly Ahmed glaucoma valve implan-tation. Although surgical rates ranging from 7.5% to 38% have been reported in the literature, these differences largely reflect variation in the pre-PK diagnoses of the study populations.^7,10,12
The main limitation of our study is its retros-pective nature. Furthermore, the inclusion of charac-teristic features of all eyes treated with PK in this study would have provided a more comprehensive contribution to the existing literature. However, there are limited studies on post-PK IOP elevation in which preexisting glaucoma was excluded. In our present study, preexisting inflammation in eyes with tectonic PK, aphakia, and the presence of PAS were found to be related to de novo post-PK IOP elevation. It is imperative to apply meticulous follow-up and efficacious treatment of these eyes to prevent potential optic disc damage that may develop due to IOP elevation, as well as to preserve graft viability.

Volume: 24 Issue: 3 March 2026

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