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Risk Factors and Incidence of Ocular Hypertension After Faik Oruc¸oglu, MD,* Eytan Z. Blumenthal, MD,w Joseph Frucht-Pery, MD,w which surgeons face after corneal transplantation surgery.
Purpose: Ocular hypertension is a potentially serious complication Since computerized visual field examination and optic nerve after penetrating keratoplasty (PKP). Our objective is to determine visualization are often limited by corneal graft clarity and the risk factors, incidence, patient characteristics, response to high refractive errors, the damage to the optic nerve is often pressure-lowering medical therapy, and graft outcome associated difficult to assess in postkeratoplasty eyes. Pressure is also with elevation of intraocular pressure after PKP.
occasionally difficult to measure accurately. As evidence of Methods: One hundred forty-six consecutive eyes that had PKP optic nerve damage after keratoplasty is difficult to ascer- between June 2001 and June 2003 were operated and managed at tain, the term “ocular hypertension” may be more appro- Hadassah-Hebrew University Medical Center. Chart review was priate than “glaucoma” in this context.
performed seeking preoperative and postoperative data on risk The reported incidence of ocular hypertension after factors for ocular hypertension after PKP. Univariate and logistic PKP is highly variable, and ranges between 11% and regression analysis were performed to identify significant risk This incidence was associated with several risk factors. These include the indication for keratoplasty, the Results: After surgery, 70 eyes (47.9%) had at least 1 period of status of the lens, additional procedures at the time of ocular hypertension, with a mean intraocular pressure (IOP) of keratoplasty, and preexisting glaucoma, as major risk fac- 27.15 ± 5.66 mm Hg. Ocular hypertension appeared after a mean tors.The majority of these studies used basic statistical postoperative period of 70.3 ± 15.8 days, and continued for an tools such as univariate analysis to identify risk factors. In average period of 15.6 ± 2.0 days. In 35 eyes (23.9%), a second addition—the distribution and time span of ocular hyper- episode of IOP elevation was noted 212.2 ± 46.8 days after thesurgery. Logistic regression analysis revealed that preexisting tension after surgery were not reported.
glaucoma (P = 0.009) and an additional surgical procedure com- This study presents the demographics, incidence, dis- bined with PKP (P = 0.007) were the main factors predicting tribution and risk factors of postkeratoplasty ocular ocular hypertension after PKP. In 11 eyes (7.53%) the topical hypertension in a large cohort of patients in a single uni- pressure-lowering therapy failed, and they required glaucoma versity medical center, using multivariate analysis to identify major risk factors leading to ocular hypertension Conclusions: The incidence of ocular hypertension after PKP is high, and at least 1 episode of high IOP was noted in almost half ofour patients. A history of preexisting glaucoma and an additionalsurgical procedure combined with PKP were found to be significant factors predicting the occurrence of ocular hypertension.
The hospital charts of all patients who underwent PKP at the Department of Ophthalmology, Hadassah University Key Words: ocular hypertension, intraocular pressure, penetrating Medical Center, between June 2001 and May 2003 were reviewed. Medical charts were retrieved from the Medical Archives Department according to diagnosis codes thatwere assigned to summary letters after discharge. Infor-mation was further obtained from the operating room logbook, and cross-checked with the data from the Medical cular hypertension is a potentially serious complica- Archives Department. During this period a total of 174 tion after penetrating keratoplasty (PKP). High PKP procedures were performed. Of these, 28 patients were intraocular pressure (IOP) may cause increased loss of excluded because of incomplete documentation, or lack of corneal endothelial cells and graft failure,and can lead to sufficient follow-up. Therefore, 146 patients met the above irreversible optic nerve The high incidence, diffi- criteria and were included in this study. All patients signed culties in diagnosing in proper monitoring, and the complex an informed consent form before surgery.
management of cases with refractory glaucoma, have The following data were collected for each patient: turned postkeratoplasty glaucoma into a major problem Age, sex, visual acuity, the presence of glaucoma beforesurgery, the number of pressure-lowering medications usedbefore surgery, diagnosis underlying the need for corneal Received for publication March 12, 2012; accepted November 5, 2012.
transplantation, previous ocular surgeries, preoperative From the *Kudret Eye Hospital, Istanbul, Turkey; and wDepartment IOP, preoperative lens status, graft and host trephination of Ophthalmology, Hadassah-Hebrew University Medical Center,Jerusalem, Israel.
diameters, suturing method, additional procedures per- Disclosure: The authors declare no conflict of interest.
formed at the time of PKP, the dosage and duration of Reprints: Faik Oruc¸oglu, MD, Kudret Eye Hospital, P.O. Box 34418, topical and systemic corticosteroids administered after surgery, time to postoperative epithelialization, intra- Copyright r 2013 by Lippincott Williams & WilkinsDOI: 10.1097/IJG.0b013e31828700f5 operative and postoperative complications, duration and J Glaucoma  Volume 00, Number 00, ’’ 2013 Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Glaucoma  Volume 00, Number 00, ’’ 2013 timing of postoperative ocular hypertensive events, numberof pressure-lowering medications which were used after surgery, and further surgical procedures. Uncorrected and best spectacle corrected visual acuity were measured by a Snellen acuity chart before surgery and at each post- operative visit. All Snellen visual acuity measurements were converted to logarithm of the minimum angle of resolution (logMAR) to allow statistical analysis.
PKP trephination of the recipient bed was performed using a Barron vacuum trephine. Donor buttons were prepared 0.25 or 0.50 mm (in cases of aphakia) larger than the recipient bed, using a Barron vacuum trephine, and were cut from the endothelial side. The donor cornea was first anchored to the host bed by 4 cardinal 10-0 nylon sutures, and by then sutured with either running or inter- Excised buttons were sent to histologic evaluation and donor rims to microbiological evaluation. Gentamicin and cefazolin were injected subconjunctivaly at the end of surgery. Topical corticosteroids, antibiotics, and systemic corticosteroids were administered after surgery, at the dis- cretion of the surgeons. Most patients received systemiccorticosteroids until epithelialization of the corneal graftwas complete. Topical corticosteroids were started at a doseof 6 to 8 times daily for the first 2 to 4 postoperative weeksand thereafter tapered down over the next 3 months to a Before surgery, the mean IOP was 13.2 ± 3.7 mm Hg frequency of 3 to 4 times daily, and maintained at this (range, 5 to 26 mm Hg). Most glaucoma patients were dosing during the first year. Thereafter, tapered to a controlled with medical or surgical treatment before sur- gery, and only 6 (4.1%) eyes had an IOP >20 mm Hgduring the preoperative examination. Thirty-three eyes (22.6%) had a history of glaucoma and/or had used pres-sure-lowering medications. Of these 33 eyes, 23 eyes Postoperative elevation of IOP was the primary out- (69.7%) used 1 pressure-lowering medication, 7 eyes come in this study. Ocular hypertension was defined as IOP (21.2%) needed 2 medications, and 3 eyes (9.1%) needed of 21 mm Hg or higher as measured with a Goldmann 3 pressure-lowering medications in the period preceding tonometer. IOP was measured postoperatively daily for 1 the surgery. Eight patients had previously undergone week, weekly for the first postoperative month, and then monthly for 6 months and during each subsequent exami- The indications for PKP are presented in nation after surgery. The occurrence of postkeratoplasty Surgical procedures before corneal transplantation ocular hypertension was determined and associated with: age, sex, preoperative corneal diagnosis, previous ocular The median recipient bed size was 8.0 ± 0.3 mm surgery, preexisting glaucoma, graft size, donor oversize, (range, 7.0 to 9.0 mm) and the donor button was oversized suturing type, lens status, and any associated surgeries by 0.25 mm in most of the patients (134 eyes, 92.4%).
combined with the PKP. The response to pressure-lowering Interrupted sutures were used in 110 eyes (75.3%), and 4 medical therapy and graft outcome were also recorded.
interrupted sutures combined with a single continuous Preoperative, surgical, and postoperative parameters suture were used in 36 eyes (24.7%).
were analyzed with SPSS (version 13; SPSS Inc., Chicago, In 21 (14.4%) patients, PKP was combined with an IL). Independent risk factors for ocular hypertension after PKP, were identified using univariate and multivariate The mean preoperative best corrected visual acuity analyses. w2 and independent samples t test were calculated improved from 0.90 ± 0.78 logMAR units (Snellen equiv- for the univariate analyses. Variables found to be sig- alent 20/160; range, 0.18 to 3.00 logMAR units) to nificant in the univariate analysis were included in a mul- 0.37 ± 0.51 logMAR units (Snellen equivalent 20/50; range, tivariable logistic regression analysis with the presence of 0.0 to 3.00 logMAR units) at the final examination ocular hypertension as the dependent variable. A P-value of (P < 0.001). The mean postoperative best corrected visual <0.05 was considered significant.
acuity and the mean preoperative best corrected visualacuity did not significantly differ for both postkeratoplasty ocular hypertension patients (P = 0.328) and in patients The mean age of the patients in this study was who did not develop ocular hypertension (P = 0.792).
45 ± 20.8 years (range, 15 to 88 y). There were 71 (48.6%) During a mean follow-up of 24.4 months, at least 1 men and 75 (51.4%) women. The mean postoperative fol- consecutive period of high IOP (Z21 mm Hg) was docu- low-up period was 24.4 ± 7.6 months (range, 12 to 42 mo).
mented in 70 eyes (47.7%) with a mean IOP of Demographic data and preoperative parameters are shown 27.1 ± 5.6 mm Hg (range, 21 to 49 mm Hg), starting after a mean postoperative period of 70.3 ± 15.8 days (1 to 720 d, Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Glaucoma  Volume 00, Number 00, ’’ 2013 TABLE 2. Indications for Penetrating Keratoplasty TABLE 4. Additional Surgical Procedures With PKP (n = 21 eyes) IOL indicates intraocular lens; PKP, penetrating keratoplasty.
eyes. The mean IOP was 29.0 ± 6.7 mm Hg (range, 21 to BK indicates bullous keratopathy; HSK, herpes simplex keratitis.
46 mm Hg) occurring 212.2 ± 46.8 days (range, 15 to 870 d)after the surgery Twenty-nine of them requirednew or additional pressure-lowering drugs. During thesecond period of ocular hypertension the IOP was nohigher compared with the first period (P = 0.403), but the 95.7% in 360 d) and lasting for a period of 15.6 ± 2.0 days number of mean topical pressure-lowering drugs sig- (1 to 90 d) Topical corticosteroids were used in 69 nificantly increased this time (P = 0.004). The mean dura- eyes and oral corticosteroids in 13 eyes of these 70 patients tion of the second period was 18.1 ± 2.9 days (range, 1 to at the time of diagnosis of ocular hypertension. Topical 60 d). During the second period of ocular hypertension 30 corticosteroids were applied for 2 to 12 times a day (mean eyes received topical corticosteroids with a mean dose of 6.0 ± 2.1 times daily), and oral prednisone was adminis- 4.6 ± 1.9 times a day (range, 2 to 10 times). Only 3 patients tered at a dose of 20 to 100 mg (mean 60.0 ± 18.2 mg daily).
received oral corticosteroid treatment. Overall, 11 eyes did Generally the topical corticosteroid was tapered down, not respond to the topical pressure-lowering therapy, and discontinued, or switched to a weaker one during the all them required glaucoma filtering surgery to control the During the periods of pressure elevation, patients who Overall complications were observed in 30 eyes had a history of preexisting glaucoma, when compared to (20.5%) during the follow-up period. Corneal graft rejec- patients without a history of preexisting glaucoma, tended tion appeared in 10 eyes, graft failure in 13 eyes, delayed to have a higher IOP (mean 29.7 ± 7.0 vs. 25.7 ± 4.2 mm epithelialization in 8 eyes, microbial keratitis in 5 eyes, and Hg, respectively, P = 0.02), earlier manifestation of ocular recurrent herpes simplex keratitis in 2 eyes. Graft failure hypertension (mean time 39.2 ± 57.4 vs. 87.6 ± 157.6 d, occured after irreversible rejection episodes in 2 patients, respectively, P = 0.014) and required a greater number of infections in 2 patients, delayed epithelialization in 1 medications (number of medications: 1.5 ± 0.7 vs. 1.1 ± patient, and herpes simplex keratitis in 1 patient. The mean 0.36, P = 0.001). The number of medications was increased period to graft failure was 12.7 ± 9.5 months (range, 2 to for patients with previous glaucoma (number of medi- 28.3 mo) after PKP. Nine of 13 failed grafts occurred in cations: 1.5 ± 0.7 vs. 1.3 ± 0.6, P = 0.009).
patients who had at least 1 postoperative episode of ocular A second episode of postoperative ocular hypertension hypertension. However, this higher rate did not reach after control of first episode was observed in 35 of these 70 statistical significance compared to graft failures in TABLE 3. Previous Ocular Surgery (n = 70) Retina detachment repair + cataract surgery FIGURE 1. The mean starting time and mean length of periodswith ocular hypertension after penetrating keratoplasty. Values AMT indicates amniotic membrane transplantation; ECCE, extrac- apsular cataract extraction; LKP, lamellar keratoplasty; PKP, penetrating are mean ± SE in days after surgery. Start—mean time from sur- keratoplasty; PRK, photorefractive keratectomy.
gery until ocular hypertension was first noted; Duration—meanduration of period with ocular hypertension.
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J Glaucoma  Volume 00, Number 00, ’’ 2013 not found to be significant. For eyes that had a preexisting TABLE 5. Logistic Regression Analysis of Risk Factors glaucoma, no other significant risk factors were identified When the 70 eyes with postkeratoplasty ocular hypertension were divided to early-onset ocular hyper-tension [up to 1 mo, n = 43 (29.5%)] and late-onset [ > 1 mo, n = 27 (18.5%)] no significant differences in the risk factors was noted between these 2 groups (P val- Glaucoma is a serious complication after PKP. This study evaluated the incidence and risk factors for post- keratoplasty ocular hypertension. Univariate analysis identified risk factors significant for this condition, includ- ing preexisting glaucoma, previous ocular surgery, donor oversize of 0.5 mm, additional surgical procedures com- bined with PKP, pseudophakia, and aphakia. Parameters including age, sex, laterality, indication for PKP, graft size,and type of suturing were not significantly related to Significant variables in the univariate analysis were included in the postoperative IOP elevation in the univariate analysis.
Bold values indicate statistically significant.
Multivariate analysis further showed that preexisting *Dependent variable: postkeratoplasty IOP elevation.
glaucoma and surgeries combined with PKP were the only CI indicates confidence interval; IOP, intraocular pressure; OR, odds 2 significant risk factors found for the occurrence of ocular The overall incidence of at least 1 consecutive period of ocular hypertension after PKP in our study was 47.7%.
The reported incidence of glaucoma after PKP in previousreports ranges between 7.3% and 33.6%. Our higher inci- nonhypertensive patients (P = 0.107), perhaps because of dence may be because of higher incidence of preoperative limited power in this study. Preexisting glaucoma also did glaucoma in our patients (22.6%), the frequency of IOP not show statistically significant effect on graft failure measurements taken, and combined procedures with PKP Univariate analysis was performed to identify individ- When patients with ocular hypertension in our study ual risk factors for postkeratoplasty ocular hypertension. In were subdivided according to the time of onset, the inci- this analysis—age, sex, the indication for keratoplasty, the dence was 29.5% in the early postoperative period size of graft, and the type of suturing—were not found to be (< 1 mo), and only 18.5% in the late (> 1 mo) postoperative significant risk factors for postoperative ocular hypertension period. Similarly, several studies have divided ocular (w2 test, P values—0.07 to 0.579). In contrast, the following hypertension into early and late onset and characterized the factors were found to be significant risk factors affecting incidence and risk factors for these 2 periods. Irvine and Kaufmanfound that during the first postoperative week, (P < 0.001), previous ocular surgery (P < 0.014), donor the majority of their patients suffered from ocular hyper- oversize of 0.50 mm (P < 0.01), additional surgical proce- tension of Z25 mm Hg. Karesh and Nirankarinoted an dures at the time of keratoplasty (P < 0.001), pseudophakia incidence of early ocular hypertension in 31%, and chronic IOP elevation in 29% of 80 eyes after keratoplasty.
Risk factors identified by univariate analysis were sub- Goldberg et aldocumented early and late ocular hyper- jected to multivariate logistic regression analysis. Using mul- tension in 23% and 35%, respectively, of eyes after tivariate logistic regression analysis, only 2 risk factors were found to be associated with postoperative ocular hyper- tension: preexisting glaucoma [odds ratio (OR), 6.23; 95% combined with PKP were the leading risk factors for ocular confidence interval (CI),1.59-24.36; P = 0.009] and an addi- hypertension, as identified in our study, using logistic tional intraocular surgical procedure at the time of kerato- regression analysis. Only 1 previous study had analyzed risk plasty (OR, 13.08; 95% CI, 2.04-83.91; P = 0.007; ).
factors using multivariate logistic regression Since preexisting glaucoma was a major risk factor for Chien et found preexisting glaucoma and additional postoperative ocular hypertension, a separate logistic procedures as risk factors using logistic regression analysis, regression analysis was performed for eyes without preex- but that study looked only at the immediate postoperative isting glaucoma and for eyes with preexisting glaucoma.
period (1 wk). Several other studies identified preexisting Independent variables included previous ocular surgery, glaucoma as a risk factor for postkeratoplasty ocular donor oversize of 0.50 mm, additional surgical procedures hypertension Jonas et alreported that on the combined with keratoplasty, pseudophakia, and aphakia.
first postoperative day the IOP was significantly higher than For eyes without preexisting glaucoma, the only significant that before keratoplasty, the main predisposing factor risk factor for the occurrence of postkeratoplasty ocular being preexisting high IOP. Preexisting history of glaucoma hypertension was an additional surgical procedure (OR, was found to be responsible for higher graft On 14.85; 95% CI, 1.96-112.62; P = 0.009). Other factors were the day of admission for PKP only 6 (3.5%) eyes in our Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Glaucoma  Volume 00, Number 00, ’’ 2013 TABLE 6. Previous Studies on Postkeratoplasty Ocular Hypertension AC indicates anterior chamber; BK, bullous keratopathy; IOL, intraocular lens; PAS, peripheral anterior synechia; PBK, pseudophakic bullous study had IOP of Z21 mm Hg, indicating that even when Mechanisms explaining an IOP rise after PKP include glaucoma was medically controlled, ocular hypertension the following: postoperative edema and inflammation could follow PKP if glaucoma preceded the surgery.
compromising the trabecular meshwork, angle distortion, The second significant risk factor was the combination peripheral anterior synechiae, retained viscoelastics, and a of PKP with another surgical procedure, usually cataract steroid response. Olson and using a mathe- extraction with intraocular lens implantation. A combined matical model, identified several surgical variables that procedure was performed in 14% of our patients at the time could potentially alter the anterior chamber angle and of PKP. Other studies have also reported combined proce- increase the IOP. According to this model, tight suturing, dures to be a major risk factor for postkeratoplasty ocular long suture bites, larger trephine sizes, same-sized donor- hypertension Other reported risk factors for recipient trephination, and increased recipient peripheral the development of postkeratoplasty ocular hypertension are corneal thickness were all related to iridocorneal angle aphakia, presence of anterior synechiae, and indications for compression and an IOP increase. Using same sized grafts keratoplasty such as trauma, regraft, and bullous keratop- may distort and collapse the angle thus causing decreased In the present study, previous ocular sur- outflow and increased IOP. Zimmerman et alobserved a gery, donor oversize of 0.50 mm, additional intraocular sur- higher incidence of postkeratoplasty glaucoma in aphakic geries, pseudophakia, and aphakia were risk factors identified eyes or in combined procedures when same size donor by univariate analysis. Most previous studies identified buttons were used. The IOP was greater in larger corneas.
aphakia as a significant risk factor Olson and Again, Zimmermann et showed that using same size Kaufmanstudied aphakic keratoplasty, and reported an donor buttons in aphakic keratoplasty resulted in a 37% incidence of IOP >35 mm Hg in the first postoperative week reduction of outflow facility. This did not occur with 0.50- in 46% of 81 aphakic eyes. In our study aphakia was indeed a mm oversize donor button in phakic keratoplasty. Other significant risk factor when analyzed separately, but was not studies, however, did not find a significant effect of graft found to be an independent predictor when multivariate oversizing by 0.5 mm on postkeratoplasty ocular hyper- tension.Interestingly, oversizing the grafts by 0.50 mm Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Glaucoma  Volume 00, Number 00, ’’ 2013 was one of the predisposing factors for ocular hypertension carefully monitored after the procedure. Additional pro- in our study, but only a small proportion of patients had cedures during PKP increase the risk of postoperative this oversizing. This effect was most likely associated with ocular hypertension. Surgeons should probably consider aphakia, as 0.5-mm oversized donors were applied to the risk associated with combined procedures, and perhaps aphakic patients. Having used multivariate analysis, both consider the possibility of staged procedures. The intro- factors were eliminated as risk factors for postoperative duction of lamellar techniques for corneal transplantation glaucoma. Other possible explanations for the increased may further decrease the incidence of postkeratoplasty risk in 0.5 mm oversizing is that these grafts are usually larger. Larger donor buttons may affect the iridocornealangle. Indeed, Panda et noted an incidence of post-operative glaucoma of 37% in eyes with 10-mm grafts, versus 14% in eyes with 6 to 7.5-mm grafts. Steroids play 1. Charlin R, Polack FM. The effect of elevated intraocular an important role in the pathogenesis of glaucoma. Post- pressure on the endothelium of corneal grafts. Cornea. 1986;1: operative use of steroids controls inflammation and reduces the likelihood of peripheral anterior synechia, thus reducing 2. Svedbergh B. Effects of artificial intraocular pressure elevation on the corneal endothelium in the vervet monkey (Cercopi- the risk of IOP elevation. In contrast, topical steroids may thecus ethiops). Acta Ophthalmol (Copenh). 1975;53:839–855.
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glaucoma and corticosteroid-induced ocular hypertension Elevated intraocular pressure after aphakic keratoplasty: (CIOH) and the penetration of topical 0.5% cyclosporine iatrogenic disease and prevention. Ann Ophthalmol. 1978;10: A into the cornea and anterior chamber. CLAO J. 1998;24: Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.


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