share Send us an email: hsijournal@ug.edu.gh Visit us: https://www.hsijournal.ug.edu.gh ISSN Online 2704-4890 ISSN Print 2720-7609 Online first publication Orig inal Research Article HSI Journal (2023) Volume 4 (Issue 1):448-456. https://doi.org/10.46829/hsijournal.2023.6.4.1.448-456 Open Incidence and risk factors of steroid-induced ocular Access hypertension following pterygium excision with conjunctival autograft Raymond DK TOSEAFA 1, 2,, Imoro Z BRAIMAH 2, 3*,, Naa N TAGOE 2, Benjamin ABAIDOO 2, 3, Yakubu S ADAM2, Edith M DOGBE 2,3, Vera A ESSUMAN 2, 3 1 Department of Surgery, Cocoa Clinic, Ghana Cocoa Board, Accra, Ghana; 2 Lions International Eye Centre, Korle-Bu Teaching Hospital, Accra, Ghana; 3 Department of Surgery, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana Received July 2022; Revised September 2022; Accepted January 2023 Abstract Background: Topical steroids are used to reduce post-operative inflammation after ocular surgery with the potential risk of ocular hypertension, glaucoma and blindness. There is a paucity of published data globally and locally on steroid-induced ocular hypertension (SiOH) post pterygium excision (PE) with conjunctival autograft (CAG). Objective: We aimed to determine the incidence and risk factors of SiOH post-PE with CAG in Korle-Bu Teaching Hospital, Accra, Ghana. Methods: In this prospective observational study, the demographic and clinical data of patients undergoing PE with CAG were collected and analyzed. Post-operative intraocular pressures (IOP) were measured on days 1, 7, 14, 28, and 42. The cumulative incidence of SiOH (proportion of the increase in IOP ≥ 10mm Hg at six weeks compared to baseline) and mean change in IOP from baseline were computed. Risk factors of SiOH were determined using a multiple logistic regression model. The Kaplan-Meier survival curve was used in estimating the median time to develop SiOH. Results: Overall, 101 patients participated in this study with a mean age of 46.8 ± 11.9 years. The majority (65.3%, n= 66/101) of participants were females. The mean pre-operative IOP in the study eyes was 15.3 ± 3.0 mm Hg. The overall mean post-operative IOP was 18.6 ± 2.8 mm Hg (p = 0.001). The overall incidence of SiOH six weeks post-PE with CAG was 32.7% (95% confidence interval (CI) = 23.7 - 42.7%). Male sex was the only independent factor associated with the development of SiOH [odds ratio (OR) = 3.3; 95% CI = 1.1 - 9.7; p = 0.032]. The median time to develop SiOH was 42 days (95% CI = 37.1 - 46.9 days, p = 0.022). Conclusion: The study showed that SiOH post-PE is a common complication with an overall six-weeks post-excision incidence of 32.7%. Males are more likely to develop SiOH after PE with CAG. Patients undergoing PE with CAG should be closely monitored postoperatively to prevent complications associated with prolonged raised IOP. Keywords: Pterygium excision, conjunctival autograft, steroid, intraocular pressure, ocular hypertension Cite the publication as Toseafa RDK, Braimah IZ, Tagoe NN, Abaidoo B, Adam YS, Dogbe ME, Essuman VA (2023) Incidence and risk factors of steroid-induced ocular hypertension following pterygium excision with conjunctival autograft. HSI Journal 4(1):448-456. https://doi.org/10.46829/hsijournal.2023.6.4.1.448-456 INTRODUCTION Ocular hypertension (OH) is a well-recognized complication of corticosteroid use [3]. The incidence of Corticosteroids are used to reduce inflammation after steroid-induced ocular hypertension (SiOH) varies with the ocular surgery. They suppress cellular infiltration, potency, concentration and formulation of the steroid, vascular permeability, fibroblast proliferation, leukocyte frequency of dosing and duration of treatment [2]. The migration, collagen deposition and scar formation [1,2]. ocular hypertensive effects of steroids are caused by an increase in outflow resistance and a reduction in the outflow * Corresponding author of aqueous humor through the outflow channels at the level Email: zebaimoro2000@yahoo.com of the trabecular meshwork [4]. The higher the potency of Copyright © 2023 University of Ghana College of Health Sciences on behalf of HSI Journal. All rights reserved. 4 4 8 This is an Open Access article distributed under the Creative Commons Attribution 4.0 License. Visit or download articles from our website https://www.hsijournal.ug.edu.gh. Steroid-induced ocular hypertension share Tose afa et al., 2023. https://doi.org/10.46829/hsijournal.2023.6.4.1.448-456 Send us an email: hsijournal@ug.ed u.gh Visit us: https://www.hsijournal.ug.edu.gh a corticosteroid preparation, the earlier the onset and the whether systemic or local and those who could not be stronger its ocular hypertensive effect [3]. The examined using an applanation tonometer. The sample size predisposing factors for steroid-induced ocular for this observational study was calculated using the hypertension (SiOH) include a history of primary open- formula N = 2(Zα+ Zβ) (Zα+ Zβ) (SD) 2 / [E] 2 [14], where angle glaucoma, glaucoma suspect, a first-degree relative N is the total number of participants to be recruited in the of glaucoma patient, previous history of SiOH, very young study, Zα is the type 1 error set at 5% with a corresponding (< 10 years of age) and older ages (>50 years of age), high z score of 1.96, Zβ is the type 2 error set at 20% with a myopia, type 1 diabetes mellitus, connective tissue disease, corresponding z score of 0.84, SD is the standard deviation male sex, and genetic and racial factors [2-7]. Although the of the 1-day post-operative mean IOP = 4.3 mm Hg based elevation of Post-operative intraocular pressures (IOP) on the study by Wu et al. [7]. The effect size E is 2.3 based reduces upon cessation of steroid therapy, it may lead to on the study by Wu et al. [7]. Accounting for a 20% loss to glaucoma and blindness if not detected early and treated follow-up, a minimum of 66 participants were required. appropriately [2]. Pterygium is a common eye condition Data collection with a higher prevalence reported in the tropics [8]. The A pre-tested structured questionnaire was used to collect definitive treatment is surgical. Recurrence following preoperative and postoperative data from the participants. pterygium excision can be reduced using conjunctival Demographic characteristics of study participants obtained autografts or amniotic membrane transplant [8]. Adjunctive included; age, sex and occupation of patients. Medical therapy involving the use of chemotherapeutic agents or history of participants was obtained and these included; the application of beta radiation to the scleral bed may also duration of pterygium (< 6 months, 6 months to 1 year, > 1 reduce recurrence but no technique is perfect [9,10]. In year), eyes affected (right, left or both), eye to be operated pterygium surgery, steroids have not only reduced the post- (right or left), the location of pterygium (nasal, temporal operative discomfort and inflammation but also the rate of and both), history of previous eye trauma, history of recurrence [11]. Topical administration is the most previous eye surgery, wearing of spectacles, history of common mode of application of steroids in ophthalmology. glaucoma, family history of glaucoma, antecedent use of Few studies on SiOH after pterygium surgery have been steroids, use of other medications that may affect IOP, drug reported [7,12,13]. The reported incidence of SiOH varies history, presence of diabetes, presence of hypertension, between 9.6% and 24% due to differences in definition and presence of connective tissue disease, and indication for criteria [7,12,13]. Furthermore, there are no published surgery. The Snellen visual acuity chart was used to assess studies of SiOH after PE with CAG in the West African the visual acuity of all participants. Assessment of the sub-region. In this manuscript, we report the incidence and adnexa, anterior segment, and fundi was examined by determinants of SiOH after pterygium excision with a biomicroscopy using the slit lamp binocular microscope conjunctival autograft at Korle-Bu Teaching Hospital with a Volk™ +90D lens (Volk, USA). Clinical (KBTH), Accra, Ghana. staging/grading of pterygium was performed and the date of the surgery was scheduled. MATERIALS AND METHODS Intraocular pressure (IOP) measurement of both study and Study design and settings fellow eyes was done using a slit lamp binocular This prospective cohort study aimed to evaluate the microscope with mounted calibrated Goldmann occurrence and factors associated with steroid-induced applanation tonometer (GAT) (Köniz, Switzerland) after ocular hypertension (SiOH) following pterygium excision instillation of fluorescein 2% with tetracaine 2% drops. One (PE) with conjunctival autograft (CAG). The study was reliable GAT mounted on a Haag Streit Slit lamp was conducted at the Lions International Eye Center (LIEC) of deployed for use at the designated study area with the KBTH from September 2019 through March 2021. The ergonomically comfortable arrangements for the work. To LIEC is a tertiary teaching facility and has a full ensure consistency of readings, pre-test runs were complement of staff for effective Eye Health delivery. conducted by comparing the readings of two experienced Ocular surgeries, laser procedures, and various ophthalmic ophthalmologists. The goal was to achieve an acceptable diagnostic investigations and imaging are carried out at the level of interobserver variability, with readings correlated facility. About 20 new cases of pterygium are recorded within 2 mmHg of each other. The GAT was calibrated monthly at the clinic. each day before measurements began and an average of Study population three readings within 1 mm Hg of each other was taken. The guidelines for measuring IOP using applanation tonometry Adults who were diagnosed with primary pterygium and were followed. If a reading required corroboration and were over 18 years old, and who provided written informed confirmation, as in the recording of an outcome measure, consent, were enrolled in the study if they agreed to the investigators referred it to another Ophthalmologist undergo PE with CAG and attend follow-up consultations who was blinded to the reading of the PI. The confirmatory as specified in the study protocol. Patients with pterygium IOP reading, if in the agreement was used as the reading for requiring excision were excluded from the study if they had the participant. The study began before the onset of the prior intraocular surgery in the affected eye, recurrent novel Coronavirus disease (COVID-19) pandemic. To pterygium, previous history of SiOH, current use of steroids ensure the safety of study participants and investigators Copyright © 2023 University of Ghana College of Health Sciences on behalf of HSI Journal. All rights reserved. 449 This is an Open Access article distributed under the Creative Commons Attribution 4.0 License. Visit or download articles from our website https://www.hsijournal.ug.edu.gh Steroid-induced ocular hypertension share Tose afa et al., 2023. https://doi.org/10.46829/hsijournal.2023.6.4.1.448-456 Send us an email: hsijournal@ug.ed u.gh Visit us: https://www.hsijournal.ug.edu.gh during the COVID-19 pandemic, the following protocols was applied for an emollient effect and the eye was padded. were implemented: study investigators and participants Oral analgesic medications were prescribed after the were required to wear face masks, and hand washing was surgery including acetaminophen 1g tablets three times a mandatory. The temperatures of participants and the day and diclofenac tablets 75 mg twice daily, all for 5 days. investigators were taken with a non-contact thermometer Follow-up and post-operative care gun before entry into the clinic. Participants were required The participants were seen on the following day and the eye to observe social distancing of at least 2 meters in the patches were removed. The eyes were cleaned, and Snellen waiting area. Pens and tools used for consenting were visual acuity was recorded. The IOPs were then measured sanitized with alcohol-based hand sanitiser. The and recorded and guttae dexamethasone and polymyxin B investigators wore a face mask, gloves, gown and a plastic compound preparation were given to the patients to be shield over the eyes. At the consulting room, study applied every three hours of their waking hours up to six participants were given an alcohol-based sanitiser to times a day. The clients were given their follow-up date at sanitize their hands before the start of the examination. the current visit and reminded of their appointment during Appropriate physical distance was observed. A special the week before the visit. Post-operative visual acuities and plastic breath shield was fixed on the slit-lamp machine to intra-ocular pressures were further measured on days 7, 14, protect investigators and participants from any possible 28 and 42 by Goldmann applanation tonometry. The contamination from an aerosol exchange. Participants were measured IOP values were documented, and any values that told to refrain from speaking during slit lamp procedures met the study limits were considered indicative of SiOH until completion. There was disinfection of instruments and flagged accordingly. To ensure accuracy, a team including slit lamp biomicroscope and applanation member was tasked with validating the SiOH diagnosis, tonometer after examination of each patient using 70% which was then recorded. Treatment with steroids was alcohol. discontinued upon confirmation of SiOH, and replaced with Pterygium excision with conjunctival autograft diclofenac, timolol, and tear substitutes. Participants had a All participants were taken through the Eye Center’s follow-up review one week after the initial visit. If their IOP system of booking, listing and preparation for surgery. The was normal, they had another review in a month and blood pressure of participants was measured on the day of continued the same treatment. If their IOP was still normal surgery. Participants were counselled on the surgical after a month, they received tear substitutes and non- technique to be deployed and informed consent for surgery steroidal anti-inflammatory drug drops until the graft was was obtained. In preparation for surgery, 0.4% gutt fully taken. The participants were counselled on the benoxinate hydrochloride (Benox®, Egypt) anaesthetic potential risks associated with the use of steroids and drops were instilled in the inferior fornix and the patient advised to inform any physician who offers them steroid asked to close the eye. Then, a 10% povidone-iodine treatment about the risk of developing steroid-induced solution was used to prepare the skin of the eyelids and ocular hypertension and subsequent glaucomatous optic adnexa of the study eye. The eye was then draped with neuropathy. Subsequently, participants were referred to sterile towels with a hole for the eyelets. More drops of the general ophthalmology clinics for scheduled monitoring. topical anaesthetic were applied with a 5% povidone Iodine Participants who completed the study but did not record solution. A lid speculum was used to part the eyelids and primary outcome measures were followed up for an expose the globe. Subconjunctival injection of 2% additional month after completing the initial 42-day period. lidocaine with adrenaline with 0.5% bupivacaine in a 1:1 During this time, steroid treatment was gradually tapered proportion was administered in the inferior fornix to raise a off over the course of approximately one month, while bleb and provide further anaesthesia. The pterygium was participants were still monitored for adverse events. mobilized and excised at a variable distance from the Participants were then put on tear substitutes. Adverse limbus. The head and neck were removed from their cornea events were monitored on a visit-by-visit basis, and any adherence with a size 15 scalpel blade mounted on a Bard patients experiencing adverse events were promptly Parker handle. The cornea was then polished with careful managed. superficial keratectomy. Tenon’s fascia was excised from Outcome measures the sclera and adjacent areas in the retracted segment of the The primary outcome measure was the incidence of SiOH pterygium, being careful to spare any fibres of the superior at 42 days postoperative. We defined SiOH as a clinically oblique and medial rectus muscles to obtain a clean and significant postoperative elevation of IOP by a reading of ≥ bare sclera. The anaesthetic solution of lidocaine and 10 mm Hg from baseline IOP measurement with a bupivacaine was then injected into the superior fornix and Goldmann applanation tonometer [7]. The secondary spread supero-temporally and evenly to raise a bleb for outcome measures included the incidence of SiOH on days harvesting of the free graft. A pair of Westcott scissors and 1, 7, and 28, as well as the mean IOP on days 1, 7, 28, and forceps were used to harvest the graft. This was estimated 42 post-operation. In this study, SiOH was classified based to meet the dimensions of the bare sclera defect. The graft on its severity, with high responders being those with an was then sutured in place with size 8-0 braided absorbable IOP of ≥ 16 mm Hg, moderate responders having an IOP of ophthalmic suture. Guttae dexamethasone with 6 - 15 mm Hg, and non-responders having an IOP of ≤ 5 chloramphenicol and tetracycline compound preparation Copyright © 2023 University of Ghana College of Health Sciences on behalf of HSI Journal. All rights reserved. 450 This is an Open Access article distributed under the Creative Commons Attribution 4.0 License. Visit or download articles from our website https://www.hsijournal.ug.edu.gh Steroid-induced ocular hypertension share Tose afa et al., 2023. https://doi.org/10.46829/hsijournal.2023.6.4.1.448-456 Send us an email: hsijournal@ug.ed u.gh Visit us: https://www.hsijournal.ug.edu.gh mm Hg [16]. Additionally, risk factors for SiOH and the centre for pterygium excision. Other reasons included median time to develop SiOH were also measured. participants’ personal decisions, willingness to undergo surgery, and the fear of pterygium growth extending to Statistical analysis cover the visual axis. The demographic and clinical Data were analyzed with IBM SPSS Statistics for characteristics of participants are summarized in Table 1. Windows, Version 23.0. The mean, standard deviation (SD), and independent t-test were used for comparing Table 1: Demographic, clinical characteristics and incidence of continuous data, and percentages to track IOP increase over SiOH six weeks post-pterygium excision with conjunctival time. The Chi-square test of independence was performed autograft. on categorical variables to determine if there was a Factor Number with Total number Incidence of significant association. The mean rise in IOP after SiOH in the group in the group SiOH (%) treatment with topical steroids post pterygium excision Age: with CAG was analyzed and presented as mean differences 18-30 3 7 42.9 and percentages. The incidence of SiOH six weeks post- 31-45 17 47 36.2 > 45 13 47 27.7 pterygium excision with conjunctival autograft was All ages 33 101 32.7 calculated and presented in percentage. Univariate and Sex multivariate logistic regression analyses were performed to Male 17 35 48.6 determine demographic characteristics and risk factors for Female 16 66 24.2 SiOH in clients undergoing pterygium excision with Occupation conjunctival autograft. Corresponding odds ratios and Indoor 15 47 31.9 confidence intervals (CI) were calculated. The Kaplan- Outdoor 18 54 33.3 Meier survival curves were used to estimate the median Location of pterygium number of days for study participants to develop SiOH after Nasal 30 87 34.5 the excision of pterygium with conjunctival autograft using Temporal 1 3 33.3 various factors. The significance level was set at p < 0.05. Both 2 11 18.2 Grade of pterygium RESULTS II 2 3 66.7 The demographics of study participants III 25 80 31.3 Overall, 110 patients underwent pterygium excision with IV 6 18 33.3 conjunctival autograft, and the analysis included 101 patients (91.8%) who completed their follow-up schedules. *SiOH, steroid-induced ocular hypertension. The proportion of the The mean age ± SD of the 101 participants was 46.8 ± 11.9 overall incidence of SiOH for a 95% CI= 32.7% (range, 23.7 - 42.7%). The median age was 45.0 (range, 18 - 75) years. Pterygium years (range, 18 - 75 years). The majority (65.3%, n= duration: 6 months to 1 year (11.9%, n = 12), > 1 year (88.1%, n = 66/101) of participants, were females and 53% (n = 54) of 89). Pterygium location: both eyes (51.5%, n = 52), right eye them were involved in an outdoor occupation. The majority (25.7%, n = 26), left eye (22.8%, n = 23). Previous eye trauma (88.0%, n = 89) of participants had pterygium of more than (5.0%, n = 5). Connective tissue disease (1.0%, n = 1). Antecedent one-year duration and 51.5% (n = 52) of them had use of eye drops (18.8%, n = 19). Duration since last dose of steroid use = 2 to 6 weeks. Reasons for presenting for pterygium excision: pterygium in both eyes. Twenty-six (25.7%) participants ocular surface discomfort (89.8%, n = 90), advice from a health had a pterygium in the right and 23 (22.8%) had a worker (87.1%, n = 90), cosmetic considerations (69.9%, n = 70), pterygium in the left eye. Five (5.0%) participants had participants’ personal decision and willingness to undergo surgery previous eye trauma. One (1.0%) participant had (1.0%, n = 1), fear of pterygium growth extending to cover the visual connective tissue disease. Nineteen (18.8%) participants axis (1.0%, n = 1). reported antecedent use of eye drops, including topical lubricants such as methylcellulose, which was used by 7 Incidence of SiOH participants (6.9%, n = 7), steroids such as dexamethasone The overall incidence of SiOH six weeks post-PE with 0.1% with polymyxin B (3.0%, n = 3), fluorometholone CAG was 32.7% (range, 23.7 - 42.7%). The incidence for acetate 0.1% (3.0%, n = 3), dexamethasone 0.1%, age, sex, occupation, location of pterygium, and grade of polymyxin B sulfate and neomycin sulfate (3.0%, n = 3), pterygium is shown in Table 1. Among the three age hydrocortisone acetate 1.5%, neomycin sulfate and groups, the highest incidence (42.9%) of SiOH six weeks polymyxin B sulfate (1. 9%, n = 2), and dexamethasone post-PE with CAG was recorded among those aged 18 to phosphate, neomycin sulfate (1%, n = 1). The duration 30 years. Males had a higher (48.6%) incidence compared since the last dose of steroid use before study entry was 2 to females. Participants with outdoor occupation had a to 6 weeks. Most (84.6%, n = 77) participants had higher incidence (33.3%) compared to those with indoor pterygium located nasally. The majority (78.0%, n = 71) occupation. Participants with pterygium located nasally had had grade 3 pterygium. Ocular surface discomfort (89.8%, the highest incidence of 34.5% for SiOH six weeks post-PE n = 79), advice from a health worker (87.1%, n = 74), and with CAG compared to those with pterygium located cosmetic considerations (69.9%, n = 51) were the 3 most elsewhere. We classified ocular response to steroids six com mon reasons why participants presented to the eye weeks post-PE with CAG (Table 2). A total of 17 (16.8%) Copyright © 2023 University of Ghana College of Health Sciences on behalf of HSI Journal. All rights reserved. 451 This is an Open Access article distributed under the Creative Commons Attribution 4.0 License. Visit or download articles from our website https://www.hsijournal.ug.edu.gh Steroid-induced ocular hypertension share Tose afa et al., 2023. https://doi.org/10.46829/hsijournal.2023.6.4.1.448-456 Send us an email: hsijournal@ug.ed u.gh Visit us: https://www.hsijournal.ug.edu.gh Table 2: Classification of ocular response to steroids six weeks post-pterygium excision with conjunctival autograft Factor High responders ≥16 Moderate responders Non-responders Total p value mmHg 6-15 mmHg ≤5 mmHg (%) Number (%) Number (%) Number (%) Age: 0.040 18-30 3 (3.0) 1 (1.0) 3 (3.0) 7 (6.9) 31-45 11 (10.9) 16 (15.8) 20 (19.8) 47 (46.5) >45 3 (3.0) 24 (23.8) 20 (19.8) 47 (46.5) Total 17 (16.8) 41 (40.6) 43 (42.6) 101 (100.0) Sex: 0.071 Male 10 (9.9) 12 (11.9) 13 (12.9) 35 (34.7) Female 7 (6.9) 29 (28.7) 30 (29.7) 66 (65.3) Occupation: 0.595 Indoor 6 (5.9) 20 (19.8) 21 (20.8) 47 (46.5) Outdoor 11 (10.9) 21 (20.8) 22 (21.8) 54 (53.5) Location of pterygium 0.272 Nasal 15 (14.9) 38 (37.6) 34 (33.7) 87 (86.1) Temporal 1 (1.0) 1 (1.0) 1 (1.0) 3 (3.0) Both 1 (1.0) 2 (2.0) 8 (7.9) 11 (10.9) Grade of pterygium 0.202 II 2 (2.0) - 1 (1.0) 3 (3.0) III 12 (11.9) 34 (33.7) 34 (33.7) 80 (79.2) IV 3 (3.0) 7 (6.9) 8 (7.9) 18 (17.8) %, percentage Table 3: Univariate analysis of the association between demographic and clinical characteristics and the development of SiOH Risk factor With SiOH Without SiOH Total p value Number (%) Number (%) Number (%) Mean age ± SD 45.112.1 47.6  11.7 46.8 ± 11.9 0.312 Age group (%): 0.569 18-30 3 (3.0) 4 (4.0) 7 (6.9) 31-45 17 (16.8) 30 (29.7) 47 (46.5) >45 13 (12.9) 34 (33.7) 47 (46.5) Sex (%): 0.013* Male 17 (16.8) 18 (17.8) 35 (34.7) Female 16 (15.8) 50 (49.5) 66 (65.3) Total 33 (32.7) 68 (67.3) 101 (100.0) Occupation (%): 0.525 Indoor 15 (14.9) 32 (31.7) 47 (46.5) Outdoor 18 (17.8) 36 (35.6) 54 (53.5) Duration of pterygium: 0.549 6 months to 1 year - 3 (3.1) 3 (3.1) > one year 33 (33.7) 62 (63.3) 95 (96.9) Pre-operated IOP for the eye to be 14.6 ± 3.0 15.6 ± 2.8 15.3 ± 3.0 0.131 operated (mean ± SD) Location of pterygium (%) 0.554 Nasal 30 (29.7) 57 (56.4) 87 (86.1) Temporal 1 (1.0) 2 (2.0) 3 (3.0) Both 2 (2.0) 9 (8.9) 11 (10.9) Previous eye trauma (%) 2 (2.2) 3 (3.3) 5 (5.5) 0.535 Previous eye surgery (%) 3 (3.3) 9 (9.9) 12 (13.2) 0.393 Wearing of glasses (%) 10 (11.0) 24 (26.4) 34 (37.4) 0.649 Family history of glaucoma (%) 6 (6.6) 7 (7.7) 13 (14.3) 0.342 History of diabetes (%) 2 (2.2) 6 (6.6) 8 (8.8) 0.473 History of hypertension (%) 15 (5.5) 18 (19.8) 23 (25.3) 0.211 Antecedent use of steroids (%) 7 (7.8) 12 (13.3) 19 (21.1) 0.786 Grade of pterygium (%) 0.438 II 2 (2.0) 1 (1.0) 3 (3.0) III 25 (24.8) 55 (54.5) 80 (79.2) IV 6 (5.9) 12 (11.9) 18 (17.8) Total 33 68 101 *Statistically significant risk factors (p < 0.05); SD, standard deviation; SiOH, steroid-induced ocular hypertension Copyright © 2023 University of Ghana College of Health Sciences on behalf of HSI Journal. All rights reserved. 452 This is an Open Access article distributed under the Creative Commons Attribution 4.0 License. Visit or download articles from our website https://www.hsijournal.ug.edu.gh Steroid-induced ocular hypertension share Tose afa et al., 2023. https://doi.org/10.46829/hsijournal.2023.6.4.1.448-456 Send us an email: hsijournal@ug.ed u.gh Visit us: https://www.hsijournal.ug.edu.gh Table 4: Multivariate logistic regression analysis of risk factors for development of SiOH Risk factor Number with Incident rate OR p value SiOH/total (%) (95% CI) Age: 0.945 18-30 3/7 42.9 0.9 (0.1-7.2) 0.469 31-45 17/47 36.2 0.7 (0.2-2.0) >45 13/47 27.7 Reference Sex: Male 17/35 48.6 3.3 (1.1-9.7) 0.032* Female 16/66 24.2 Reference Occupation: Indoor 15/47 31.9 1.1 (0.4-3.0) 0.861 Outdoor 18/54 33.3 Reference Location of pterygium: 0.197 Nasal 30/87 34.5 0.3 (0.1-1.8) 0.782 Temporal 1/3 33.3 0.6 (0.1-14.4) Both 2/11 18.2 Reference Previous eye trauma 2/5 40.0 0.8 (0.1-6.7) 0.801 Previous eye surgery 3/12 25.0 1.5 (0.2-9.8) 0.695 Family history of glaucoma 10/13 76.9 0.8 (0.2-3.0) 0.702 History of diabetes 2/8 25.0 0.9 (0.1-6.6) 0.972 History of hypertension 15/23 65.2 1.5 (0.4-5.8) 0.543 Antecedent use of steroids 7/19 36.8 0.8 (0.2-3.5) 0.800 SiOH, steroid-induced ocular hypertension; OR, odds ratio; CI, confidence interval; %, percentage Rise in intraocular pressure Overall, there was a mean rise in intraocular pressure after treatment with topical steroids post-pterygium excision. At baseline, the mean pre-operative IOP was 15.3 ± 3.0 mm Hg (range, 10.0 - 21.0 mm Hg). The overall mean post- operative IOP was 18.6 ± 2.8 mmHg (range,13.8 - 25.4 mm Hg) with a 21.6% increase in IOP from baseline (p = 0.001). The intraocular pressure on day 1 post-operation was 16.4 ± 3.4 mm Hg, which represents a 7.2% increase from the baseline (p = 0.006). Similarly, the mean IOP for day 7 post-operation was 17.0 ± 3.7 mm Hg with an 11.1% increase from the baseline (p = 0.001). The mean intraocular pressure for day 14 post-operation was 18.6 ± Figure 2: Line chart of mean rise in intraocular pressure between 4.9 mm Hg, corresponding to an increase of 21.6% from the operated eye and fellow eye after treatment with topical baseline (p = 0.001). On day 28, the mean post-operation steroids post pterygium excision. *Post-op, post-operation. intraocular pressure was 19.3 ± 7.4 mm Hg with a percentage rise of 26.1% (p = 0.001) and on day 42, the participants were high responders, 41 (40.6%) were mean post-operation IOP was 20.2 ± 7.1 mm Hg with a moderate responders, and 43 (42.6%) were non-responders percentage rise of 32.0% (p = 0.001). Figure 2 presents the (Table 2). average increase in intraocular pressure (IOP) between the operated eye and the fellow eye following treatment with Risk factors of SiOH topical steroids post-pterygium excision. Before surgery, The univariate analysis showed that male gender (p = there was no significant difference between the mean IOP 0.013) was significantly associated with the development of the operated eye and the fellow eye (p = 0.207). Also, no of SiOH in patients who underwent PE with CAG, as seen significant difference in mean IOP between operated eyes in Table 3. The multivariate logistic regression analysis and fellow eyes was observed a day after the excision of revealed that male gender was the only risk factor for the pterygium (p > 0.05). Statistically significant differences in development of SiOH in patients undergoing PE with CAG, mean IOPs were observed from post-operation day one with an odds ratio of 3.3 (95% CI = 1.1 - 9.7; p = 0.032). onwards (p < 0.05). Males were 3 times more likely to develop SiOH compared with females (p = 0.032). The incidence of SiOH in males Survival analysis for time to develop SiOH and females was 68.6 per hundred persons and 40.9 per The median time to develop SiOH after PE with CAG was hundred persons, respectively (Table 4). 42.0 days (Figure 3). The median time to develop SiOH Copyright © 2023 University of Ghana College of Health Sciences on behalf of HSI Journal. All rights reserved. 453 This is an Open Access article distributed under the Creative Commons Attribution 4.0 License. Visit or download articles from our website https://www.hsijournal.ug.edu.gh Steroid-induced ocular hypertension share Tose afa et al., 2023. https://doi.org/10.46829/hsijournal.2023.6.4.1.448-456 Send us an email: hsijournal@ug.ed u.gh Visit us: https://www.hsijournal.ug.edu.gh (a) (b) (c) (d) Figure 3: Kaplan-Meier survival curve for time to development of steroid-induced ocular hypertension (SiOH) (a) among age groups (b) between males and females (c) grades of pterygium (d) indoor and outdoor occupation (e) location of pterygium (e) Copyright © 2023 University of Ghana College of Health Sciences on behalf of HSI Journal. All rights reserved. This is an Open Access article distributed under the Creative Commons Attribution 4.0 License. 454 Visit or download articles from our website https://www.hsijournal.ug.edu.gh Steroid-induced ocular hypertension share Tose afa et al., 2023. https://doi.org/10.46829/hsijournal.2023.6.4.1.448-456 Send us an email: hsijournal@ug.ed u.gh Visit us: https://www.hsijournal.ug.edu.gh among males and females was 42.0 days, respectively. significant increase in mean postoperative IOP on day 1, 1 There was no statistically significant difference in the week, and 1 month compared to the mean pre-operative median time to develop SiOH between age groups (p = IOP [17]. Due to the significant increase in mean post- 0.712), sex (p = 0.202), grade of pterygium (p = 0.172), and operative IOP observed on day 1 in our study and others occupation (p = 0.913). Participants with both nasal and [7,17], we hypothesize that IOP elevation observed in the temporal pterygia in the same eye had a median time to immediate post-operative period may be due to factors develop SiOH of 28 days compared to 42 days for those other than steroid response. It has been proposed that this with either nasal or temporal pterygia only (p = 0.415). raised IOP may be because of the pterygium surgery on corneal biomechanics or the effect of the surgery on the DISCUSSION downstream drainage of aqueous humour [7,17]. There are several reports of predisposing factors of SiOH [2-7]. This study is the first to determine the incidence and Kuryan et al. [17] did not observe a significant association determinants of SiOH post-PE with CAG in Ghanaians. between possible risk factors and IOP rise following This study provides important epidemiological information pterygium excision. Wu et al., on the other hand, found about pterygium for the practice of eye health in Ghana and Hispanic race and subconjunctival injection of steroids to elsewhere. The overall incidence of SiOH (IOP ≥ 10mm Hg be significantly associated with SiOH post pterygium from baseline) six weeks post-operative PE with CAG was excision [7]. In the study by Wu et al., the male gender had 32.7%. Few studies have reported the incidence of steroid- a higher incidence of SiOH post-PE, but the difference was induced ocular hypertension post-PE [7,12,13,17]. not significant [7]. Our current study supports previous Makornwattana et al. in Thailand [13] reported SiOH of findings by Busool et al. [5], Kanellopoulos et al. [6], and 9.68% among 62 subjects following PE with amniotic Manzoor et al. [18] that suggest males are more likely to membrane transplant. The outcome measure in the develop SiOH than females after photorefractive Makornwattana study was an increase in IOP of at least 10 keratectomy procedures. Further studies should be mm Hg from the pre-operative level, which is similar to our conducted to support our findings that the male gender is a study. However, there were differences between our study risk factor for SiOH after pterygium surgery. The use of and the Makornwattana study in terms of the frequency of topical steroids induces ocular hypertension over the course administration of dexamethasone eye drops, the duration of of weeks [2]. Makornwattana et al. observed a peak rise in follow-up, and the population groups studied. Compared to IOP post-pterygium excision occurring 1-month post- our current study, participants in the study by operation [13]. In our study, the median time to develop Makornwattana et al. were older (55.4 ± 11.6 years versus SiOH post-PE with CAG was 42 days. Patients will need to 46.8 ± 11.9 years), had lower pre-operative IOP (13.1 ± 2.7 be monitored for elevated IOP beyond six weeks post- mm Hg versus 15.3 ± 3.0 mm Hg), and had fewer males. operation. In the retrospective study by Wu et al. [17], the Although the mean increase in IOP week 1 post-operation probability of experiencing elevated IOP after pterygium was higher (25.8%) in the reports of Makorwattanna et al. excision was 10.91% for Africans at 1 week, 16.6% at 1 [13] compared to our current study (11.0%), the values month, and 34.8% at 3 months. were similar at 1 month (21.3% versus 26.0%). In our current study, the percentage of moderate responders was This study had some limitations. The COVID-19 similar to the findings of Makornwattana et al. (40.6% restrictions contributed to the prolongation of the study and versus 37.1%). However, it is worth noting that none of the missed appointments. Measurement of central corneal subjects in their study was a high responder [13]. thickness would have given further validation to the IOP values that were obtained and would have provided an In a retrospective study of 212 eyes, Wu et al. [7] observed additional variable for investigating the risk factors for ethnic differences in the rate of IOP rise post-PE. The SiOH. A larger sample size would also have revealed other Hispanic race had the highest incidence of IOP elevation significant factors in the regression model. However, these (65.2%) followed by Africans (23.9%) [7]. The incidence limitations do not diminish the importance of the study and rate of IOP elevation was significantly different between the results obtained. This study stands out as the first to Hispanics and Caucasians (p = 0.031), but there was no determine the incidence of SiOH after pterygium excision statistically significant difference between Hispanics and with conjunctival autograft in Ghanaian adults. Africans (p = 0.103) or Asians (p = 0.063) [7]. The observed differences in the incidence of IOP elevation post- Conclusion PE may suggest differences in genetic predisposition to SiOH post-pterygium excision with conjunctival autograft SiOH among different racial groups [7], an observation that was a common complication with an overall six weeks post- needs to be examined in further studies. Kuryan et al. operative incidence of 32.7%. The male gender was a risk conducted a retrospective chart review of pterygium factor for developing SiOH after PE with CAG. There is a excision procedures performed by residents at an institution need to closely monitor the intraocular pressure of all in New York and reported that 19.0% of eyes developed patients who undergo pterygium excision with conjunctival SiOH at 1 month. An increase in IOP > 5 mm Hg compared autograft with post-operative use of steroids to prevent to baseline was observed in 30% of the patients [17]. post-operative complications associated with persistently Sim ilar to our work, the study by Kuryan et al. reported a increased intraocular pressure. A multi-centre study with a larger sample size and longer follow-up schedule is Copyright © 2023 University of Ghana College of Health Sciences on behalf of HSI Journal. All rights reserved. 455 This is an Open Access article distributed under the Creative Commons Attribution 4.0 License. Visit or download articles from our website https://www.hsijournal.ug.edu.gh Steroid-induced ocular hypertension share Tose afa et al., 2023. https://doi.org/10.46829/hsijournal.2023.6.4.1.448-456 Send us an email: hsijournal@ug.ed u.gh Visit us: https://www.hsijournal.ug.edu.gh recommended to explore other potential risk factors as well 4. Wordinger RJ, Clark AF (1999) Effects of glucocorticoids on the trabecular meshwork: Towards a better understanding of as monitor participants who develop a slower SiOH glaucoma. Prog Retin Eye Res 18(5):629–667. https://doi.org/ response. 10.1016/s1350-9462(98)00035-4 5. Busool Y, Mimouni M, Vainer I, Levartovsky S, Sela T, Munzer DECLARATIONS G (2017) Risk factors predicting steroid-induced ocular hypertension after photorefractive keratectomy. J Cataract Refract Ethical considerations Surg 43(3):389–393. https://doi.org/10.1016/j.jcrs.2016.12.030 The study protocol was approved by the Institutional 6. Kanellopoulos AJ, Cruz EM, Ang RET, Asimellis G (2016) Higher Review Board of Korle-Bu Teaching Hospital (KBTH- incidence of steroid-induced ocular hypertension in keratoconus. IRB/00066/2019). All procedures performed in studies Eye Vis 3(1):1–8. https://doi.org/10.1186/s40662-016-0035-9 involving human participants were by the ethical standards 7. Wu K, Lee HJ, Desai MA (2018) Risk factors for early onset of the institutional research committee and with the 1964 elevated intraocular pressure after pterygium surgery. Clin Ophthalmol 12:1539-1547. https://doi.org/ 10.2147/OPTH.S1595 Helsinki Declaration and its later amendments or 92 comparable ethical standards. Written informed consent was obtained from the participants at study enrolment and 8. Clearfield E, Hawkins BS, Kuo IC (2017) Conjunctival Autograft Versus Amniotic Membrane Transplantation for Treatment of for surgery. Pterygium: Findings From a Cochrane Systematic Review. Am J Ophthalmol 182:8–17. https://doi.org/ 10.1016/j.ajo.2017.07.004 Consent to publish All authors agreed to the content of the final paper. 9. Walter WL (1994) Another look at pterygium surgery with postoperative beta radiation. Ophthal Plast Reconstr Surg 10:247– Funding 252. https://doi.org/10.1097/00002341-199412000-00004 This research was conducted with personal funds, with 10. Mahar PS, Nwokora GE (1993) Role of mitomycin C in pterygium no external sponsorship or financial support. surgery. Br J Ophthalmol. 77:433–435. https://doi.org/ 10.1136/bjo.77.7.433 Competing Interests 11. Yaisawang S, Piyapattanakorn P (2003) Role of post-operative No potential conflict of interest was reported by the topical corticosteroids in recurrence rate after pterygium excision authors. with conjunctival autograft. J Med Assoc Thail 86 (Suppl 2): S215- 23. Author contributions 12. Khatri BK, Ton H (2012) Steroid-induced ocular hypertension RDKT designed the study. RDKT, IZB, NNT, BA, YSA, following pterygium surgery. Heal Renaiss. 10(1):57–58. EMD, VAE retrieved and analysed the data, and prepared https://doi.org/ doi.org/10.3126/hren.v10i1.6009 the manuscript. All authors provided critical review and 13. Makornwattana M, Suphachearaphan W (2015) Incidence of approved the manuscript. steroid induced-ocular hypertension in postoperative pterygium excision. J Med Assoc Thail 98(1):S151–157. Acknowledgements We thank the management and staff of the Lions 14. Sharma SK, Mudgal SK, Thakur K, Gaur R (2020) How to calculate sample size for observational and experiential nursing International Eye Centre and Cocoa Clinic (Ghana Cocoa research studies? Natl J Physiol Pharm Pharmacol 10(01):11-18. Board) for their support during the conduct of this study. 10.5455/njppp.2020.10.0930717102019 Availability of data 15. Johnston SC, Williams PB, Sheppard JD (2004) A Comprehensive Data for this work is available upon reasonable request System for Pterygium Classification. Invest Ophthalmol Vis Sci 45(13):2940. from the corresponding author. 16. Armaly MF (1965) Statistical attributes of the steroid hypertensive response in the clinically normal eye: the demonstration of three REFERENCES levels of response. Invest Ophthalmol Vis Sci 4:187–197. 1. Rhen T, Cidlowski JA (2005) Antiinflammatory Action of 17. Kuryan JT, Rosenberg J, Madu A (2009) Risk factors for elevated Glucocorticoids — New Mechanisms for Old Drugs. N Engl J Med intraocular pressure after pterygium excision. Invest Ophthalmol 353(16):1711–1723. https://doi.org/10.1056/NEJMra050541 Vis Sci 50(13):903. 2. Fini ME, Schwartz SG, Gao X, Jeong S, Patel N, Itakura T (2017) 18. Manzoor H, Batool A, Akram S, Khalil I, Affi A (2020) Steroid-induced ocular hypertension/glaucoma: Focus on Relationship between post-op central corneal thickness and pharmacogenomics and implications for precision medicine. Prog steroid-induced ocular hypertension following myopic Retin Eye Res 56:58–83. https://doi.org/10.1016/j.preteyeres. photorefractive keratectomy. Adv Ophthalmol Vis Syst 2017.01.004 10(5):132–135. 3. Phulke S, Kaushik S, Kaur S, Pandav SS (2017) Steroid-induced Glaucoma: An Avoidable Irreversible Blindness. J Curr glaucoma Pract 11(2):67–72. https://doi.org/10.5005/jp-journals-l0028-1226 Thank you for publishing with Copyright © 2023 University of Ghana College of Health Sciences on behalf of HSI Journal. All rights reserved. 4 5 6 This is an Open Access article distributed under the Creative Commons Attribution 4.0 License. Visit or download articles from our website https://www.hsijournal.ug.edu.gh