Management Pediatric Steroid Induced Glaucoma

Steroid-induced ocular hypertension and glaucoma are important complications of corticosteroid therapy in children. Corticosteroids are widely used to treat ocular and systemic inflammatory disease, but topical, periocular, and systemic administration may cause clinically significant elevation of intraocular pressure (IOP). In susceptible children, persistent IOP elevation can progress to glaucomatous optic-nerve damage and visual-field loss . Steroid-induced ocular hypertension (SIOH) is commonly characterized by an IOP increase of more than 10 mmHg from baseline, while steroid-induced glaucoma (SIG) is associated with structural or functional glaucomatous damage . The pathophysiology of SIG involves increased resistance to aqueous-humor outflow at the trabecular meshwork and the inner wall of Schlemm's canal. Corticosteroid exposure has been associated with extracellular-matrix accumulation, altered protease activity, reduced endothelial phagocytosis, and other changes that impair trabecular outflow . Children may be particularly vulnerable because of their stronger steroid response, longer anticipated duration of disease, and the potential consequences of elevated IOP during visual development . Initial management generally consists of reducing or discontinuing corticosteroid exposure when clinically possible and administering IOP-lowering medication. When IOP remains inadequately controlled despite maximal medical therapy, surgical treatment is required . The choice of procedure is especially important in children because long-term medication burden, repeated surgery, conjunctival scarring, and bleb-related complications may affect ocular health over many decades .

Ab externo circumferential suture trabeculotomy (ACST) is a canal-based glaucoma procedure that creates a 360-degree incision through the trabecular meshwork, thereby bypassing the principal site of aqueous outflow resistance and facilitating access to Schlemm's canal and the collector-channel system without forming a subconjunctival filtering bleb. Although ACST has traditionally been used in the management of primary congenital glaucoma , its mechanism may be particularly relevant to steroid-induced glaucoma, in which corticosteroid-related alterations of the trabecular meshwork and juxtacanalicular tissue increase resistance to aqueous outflow. Early pediatric reports have demonstrated favorable outcomes after circumferential trabeculotomy in steroid responders; however, the available evidence remains limited, consisting predominantly of small case series .

Non-penetrating deep sclerectomy (NPDS) is an alternative surgical approach. The procedure removes deep scleral tissue, exposes Schlemm's canal, and creates a trabeculo-Descemet's window and scleral reservoir to enhance aqueous drainage. NPDS avoids full-thickness entry into the anterior chamber, but its long-term effectiveness depends partly on maintaining the scleral lake and subconjunctival filtration pathway . Postoperative scarring, bleb fibrosis, hypotony, and the need for additional interventions may limit its durability, particularly in children with active ocular-surface inflammation. Previous studies have reported variable complete and qualified success rates after NPDS in steroid-induced glaucoma , but direct comparative evidence against a canal-based procedure is lacking.

To our knowledge, no randomized controlled trial has directly compared ACST with NPDS in children with SIOH or SIG. This prospective randomized controlled trial therefore compared the efficacy and safety of ACST and NPDS over 24 months.

Patients and Methods Study Design This prospective, randomized, controlled clinical trial was conducted at the Mansoura Ophthalmic Center, Mansoura University, Egypt, between November 2020 and November 2024. The study protocol was approved by the Ethics Committee of the Faculty of Medicine, Mansoura University, and adhered to the tenets of the Declaration of Helsinki. The trial was registered with ClinicalTrials.gov (identifier: NCT04673201). Written informed consent was obtained from the legal guardians of all participants before enrollment.

Study Participants Inclusion criteria were: (1) age 7 to 17 years; (2) elevated intraocular pressure (IOP ≥ 22 mmHg) secondary to corticosteroid use that persisted after discontinuation of steroids and maximal tolerated medical therapy; (3) ability to comply with the study follow-up schedule; and (4) written informed consent from a parent or legal guardian and assent from the child when appropriate.

Steroid-induced ocular hypertension was defined as IOP ≥ 22 mmHg after corticosteroid exposure without optic-nerve or visual-field damage. Steroid-induced glaucoma was defined as elevated IOP with glaucomatous optic-disc changes (cup-to-disc ratio ≥ 0.6 or asymmetry ≥ 0.2) and/or a corresponding visual-field defect on standard automated perimetry, in the absence of other identifiable causes of glaucoma.

Exclusion criteria were: (1) history of previous glaucoma surgery; (2) other forms of glaucoma unrelated to steroid use; (3) congenital glaucoma; and (4) complicated cataract or other significant ocular comorbidity.

No patients were lost to follow-up, and all randomized eyes completed the 24-month visit. Participants were randomized in a 1:1 ratio to ACST or NPDS using a computer-generated random sequence prepared by an independent research coordinator who was not involved in recruitment, surgery, or outcome assessment. Simple randomization was used, without blocking or stratification. Allocation was concealed in sequentially numbered, sealed, opaque envelopes held by the coordinator. An envelope was opened only after eligibility had been confirmed, written consent obtained from the legal guardian, and baseline testing completed. One eye per child was randomized and analyzed. Surgeons and families could not be masked to the procedure. Masking of the examiners who measured IOP, visual acuity, and visual field was not feasible because the two operations leave visible differences (hyphema after ACST and a filtering bleb after NPDS).

Surgical Techniques All procedures were performed under general anesthesia by the pediatric glaucoma surgical team, led by the experienced glaucoma surgeon A.S.E. (first author) with the participation of D.A.E. (second author).

Group A: Ab Externo Circumferential Suture Trabeculotomy (ACST) Previously described by our group as visco-circumferential suture trabeculotomy. The detailed surgical technique has been described previously by Elwehidy et al. [13]. Briefly, a superiorly placed corneal traction suture (6-0 Vicryl) was used to expose the operative field. A superior fornix-based conjunctival flap was created, and hemostasis was achieved. A superficial rectangular scleral flap measuring 4 × 4 mm and approximately two-thirds of the scleral thickness was fashioned and carefully dissected anteriorly toward the limbus. A deeper 2 × 2 mm scleral flap was then created beneath the superficial flap, extending toward the limbus to expose the scleral spur and unroof Schlemm's canal. Viscoelastic (Healon GV; Johnson \& Johnson Surgical Vision, Santa Ana, CA, USA) was gently introduced into the ostia of Schlemm's canal using a standard 30-gauge viscocanalostomy cannula or 27-gauge Healon cannula to dilate the canal and facilitate suture advancement. This viscodilation step is an integral part of the ACST technique.

A 5-0 polypropylene suture was prepared by cauterizing its tip to create a blunt end, minimizing the risk of trauma during canal probing. The blunt suture tip was introduced into the left ostium of Schlemm's canal with microsurgical forceps and advanced circumferentially along the entire canal. Traction was then applied to approximate the two ends of the suture, completing a 360-degree trabeculotomy. The procedure concluded with closure of the scleral flap and overlying conjunctiva using 10-0 nylon sutures. All trabeculotomies were performed as standalone surgeries.

Group B: Non-Penetrating Deep Sclerectomy (NPDS) A fornix-based superior conjunctival flap was created. A superficial scleral flap (one-third scleral depth) measuring 5 × 5 mm was dissected anteriorly until clear cornea was reached. Mitomycin C (MMC) 0.02% was applied for 2 minutes using soaked sponges under the scleral flap and conjunctiva, followed by thorough irrigation with balanced salt solution. A deeper 4 × 4 mm scleral flap was then dissected anteriorly to Schlemm's canal and extended further into the cornea to create a trabeculo-Descemet's window. The deep scleral flap was excised. A collagen implant was placed to maintain the created space and secured with a single 10-0 suture. The superficial scleral flap was closed with 10-0 nylon sutures, and the conjunctiva was sutured with 8-0 absorbable sutures.

Postoperative Management In both groups, postoperative treatment included topical broad-spectrum antibiotics and corticosteroids four to five times daily, as is standard after intraocular surgery. Antibiotics were discontinued after 2 weeks, and corticosteroids were tapered over 3 weeks according to the clinical course. Long-term corticosteroid therapy was avoided whenever possible. All anti-glaucoma medications (AGMs) were routinely stopped on postoperative day 1 unless an IOP spike (defined as an intraocular pressure ≥ 25 mmHg within the first postoperative month) or a subsequent steroid response occurred.

Outcome Measures The primary outcome was the mean intraocular pressure (IOP) at 24 months. Secondary outcomes included: (1) IOP at all other scheduled postoperative time points (1 day, 1 week, 3 weeks, 3 months, 6 months, 12 months, and 18 months); (2) number of anti-glaucoma medications required; (3) complete and qualified success rates; (4) best-corrected visual acuity (BCVA) recorded in Snellen notation and converted to logarithm of the minimum angle of resolution (LogMAR); (5) visual-field mean deviation (MD); (6) postoperative complications; and (7) need for additional surgical interventions.

Intraocular pressure was measured by Goldmann applanation tonometry whenever the child was cooperative enough for slit-lamp examination; otherwise, the Perkins Mk3 hand-held applanation tonometer (Haag-Streit Diagnostics, Köniz, Switzerland) was used. The specific device employed at each visit was recorded. Topical anesthesia (proparacaine 0.5 %) was instilled immediately before every measurement. Central corneal thickness was measured by ultrasound pachymetry at the baseline visit and is reported in Table 1. All measurements were performed by the same two examiners who were masked to treatment allocation.

Definitions of Success Complete success was defined as IOP ≤18 mmHg without AGMs. Qualified success was defined as IOP ≤18 mmHg with AGMs. Failure was defined as IOP >18 mmHg despite medication, IOP <5 mmHg on 2 consecutive visits (persistent hypotony), or the need for another glaucoma intervention. After any additional glaucoma intervention, subsequent IOP and medication values were excluded from the continuous analyses (IOP and medication count), and the eye was considered to have met the failure endpoint for the success analyses.

Visual Field Testing Standard automated perimetry was performed with the Humphrey Field Analyzer (Carl Zeiss Meditec, Dublin, CA, USA) using the SITA-Faster 24-2 strategy. Children received structured pre-test familiarization; testing was paused or repeated if inattention occurred. Because SITA-Faster does not perform false-negative catch trials, reliability was assessed using the false-positive rate and gaze-tracker data. Tests were excluded if the false-positive rate exceeded 15% or if gaze tracking indicated excessive eye movement (typically >6° for more than 20% of the test duration). Because the normative database lacks pediatric controls, MD values were interpreted alongside raw sensitivities and clinical findings, with appropriate caution regarding comparisons with young-adult norms. We selected this strategy for its shorter testing time, which preserves clinically relevant central and mid-peripheral field information while reducing fatigue and improving engagement in children.

Statistical Analysis Analyses were performed with SPSS version 26.0 and R version 4.3.1. The final sample comprised 54 children (27 per group). A formal a priori sample-size calculation was not documented; the sample size was determined by the number of eligible children presenting during the recruitment period. The study is therefore interpreted as a fixed-sample trial whose findings should be regarded as hypothesis-generating.

The primary estimand was the between-group difference in mean IOP at 24 months, tested at α = 0.05. Visit-wise comparisons of IOP at the other postoperative time points were considered secondary and were adjusted for multiple testing using the Bonferroni method (α = 0.00625 for eight comparisons).All randomized eyes were analyzed according to the intention-to-treat principle. Continuous data are reported as mean ± standard deviation and compared with Welch's two-sample t-test. Because medication counts were zero-inflated, mean medication counts are reported descriptively and the proportion of eyes receiving anti-glaucoma medication at each visit was compared with Fisher's exact test (risk differences with Newcombe 95% CIs). Categorical outcomes were compared using two-sided Fisher's exact tests. Between-group comparisons of IOP, visual acuity, and visual-field mean deviation at each scheduled visit were performed with Welch's t-test. The 24-month IOP comparison was the single primary analysis (α = 0.05); visit-wise secondary comparisons were Bonferroni-adjusted. Complete and qualified success at 24 months were secondary endpoints; success curves were compared with the log-rank test and Holm adjustment. Secondary outcomes and adverse-event comparisons were exploratory. All tests were two-sided.