Ocular Surgery In Infants And Post-Op Eye Drop Risks
Overview
This clinical observational cohort study delves into the prevalence and risk factors associated with hypothalamus-pituitary-adrenal (HPA) axis suppression in infants subjected to glucocorticoid (GC) eye drops subsequent to ocular surgery, focusing on cataract and glaucoma procedures. The research aims to discern the occurrence, duration, and potential ramifications of HPA axis suppression in this vulnerable population.
The study’s scope encompassed children aged below two years, who received GC eye drops following cataract or glaucoma surgery within a specified timeframe (January 1, 2017, to December 31, 2021). Information relevant to medical history and outcomes of adrenocorticotropic hormone (ACTH) stimulation tests was gathered from patient records.
Among the cohort of 49 infants examined, 45.5% of those tested during GC eye drop treatment and 7.4% tested post-treatment cessation exhibited diagnosed HPA axis suppression. Notably, the duration of HPA axis suppression extended beyond 3 months in 8 out of 12 patients. Logistic regression analysis revealed a significant correlation between infants diagnosed with HPA axis suppression and higher GC dose relative to body weight prior to the initial ACTH test (p < 0.001). For each 0.01 mg increase in GC dose per kg per day, corresponding to an additional daily eye drop for a 5 kg infant, the odds of HPA axis suppression increased by 79% (95% CI: 1.28;2.50). Additional associations were identified between HPA axis suppression and variables such as the interval between surgery and testing (p = 0.003), age at surgery (p = 0.035), and cumulative GC dosage (p = 0.005). Notably, a subset of infants with HPA axis suppression exhibited compromised growth, while one displayed Cushing-like features; however, instances of Addisonian crisis were not observed.
This study underscores the susceptibility of infants to hypothalamus-pituitary-adrenal axis suppression upon receiving elevated daily doses of glucocorticoids via topical ocular administration. Findings recommend heightened vigilance and close clinical or ACTH monitoring for infants prescribed glucocorticoid treatment following ocular surgery. Timely detection and intervention are crucial to mitigate potential adverse effects stemming from HPA axis suppression in this vulnerable demographic.
Introduction
Detecting hypothalamus-pituitary-adrenal (HPA) axis suppression in infants can pose a clinical challenge due to its manifestation through various nonspecific symptoms like fatigue, weight loss, growth faltering, and abdominal issues. Swift diagnosis and intervention are imperative since stress-inducing events, such as surgery, trauma, or acute illness in infants with HPA axis suppression, can trigger life-threatening Addisonian crises.
The condition can be induced in infants who receive glucocorticoid (GC) treatment in different forms – oral, systemic, intra-nasal, intra-articular, inhalation, or eye drops. Particularly, infants undergoing early surgical interventions for congenital cataracts and glaucoma are at risk of HPA axis suppression due to prescribed topical ocular GC eye drops post-operatively.
Instances of HPA axis suppression following GC eye drops led to revised treatment protocols, adopting lower GC eye drop doses after infant intraocular surgery and introducing routine HPA axis suppression testing. In light of this, the current study sought to assess the prevalence and associated risk factors of HPA axis suppression in a consecutive cohort of infants who underwent cataract or glaucoma surgery. These infants received a standardized dose of topical GCs, alongside routine testing to monitor HPA axis suppression.
The study aims to enhance our understanding of the occurrence and predictors of HPA axis suppression in this vulnerable demographic, shedding light on how standardized protocols and monitoring strategies can contribute to improved management and patient outcomes.
Method
This study delved into the effects of standardized post-operative treatment using topical glucocorticoid eye drops in infants who underwent eye surgery for congenital cataracts or glaucoma. The study’s target cohort encompassed infants operated between 1 January 2017 and 31 December 2021, at a prominent pediatric eye surgery center in Denmark. Medical records were thoroughly reviewed, capturing essential data such as gestational age, sex, birth weight, comorbidities, growth metrics, surgical details, GC dose and duration, adverse events, and diagnostic outcomes related to hypothalamus-pituitary-adrenal (HPA) axis suppression.
Inclusion Criteria
– Infants who underwent surgical interventions for congenital cataracts or glaucoma
– Surgical procedures performed at the designated tertiary pediatric eye surgery center in Denmark
Exclusion Criteria
– Cases falling outside the study period (1 January 2017 to 31 December 2021)
– Infants who did not receive standardized post-operative GC treatment with topical eye drops
– Cases where essential medical records were unavailable or incomplete
The study adhered to ethical guidelines and was approved by the Danish Data Protection Agency. Surgical interventions were conducted for cataracts by weeks 5-8 of age, while those for glaucoma were performed promptly. GC treatment comprised specific regimens based on surgery type, with dose adjustments tailored to post-operative inflammation levels.
The ACTH stimulation test was conducted around the fourth week post-surgery to assess HPA axis suppression. Serum cortisol levels were measured before and after ACTH administration, and results were evaluated by a pediatric endocrinologist. If suppression was detected, hydrocortisone substitution was initiated, and follow-up ACTH tests were conducted periodically until remission, in accordance with the clinical course. The study aimed to shed light on the impact of standardized GC treatment and testing protocols on HPA axis suppression in infant patients undergoing eye surgery.
Statistical Analysis
The statistical analysis of the study data was carried out using the software version 1.4.1717 of R, a widely used programming language and environment for statistical computing. The study primarily dealt with numerical data, which were presented using percentages, medians, and interquartile ranges. To compare groups, Fisher’s exact test was employed.
The children involved in the study were categorized into two groups based on the outcome of the ACTH stimulation test, which assessed HPA axis function (normal/insufficiency). To ensure the validity of statistical tests, the normality of data distribution was assessed using QQ-plots and histograms. If needed, data quantities were transformed logarithmically. The F-test was utilized to evaluate variance between data sets.
Various parameters were compared between the two groups to discern potential differences and associations. These parameters included gestational age, birth weight, age and weight at the time of surgery, cumulated GC dose, days between surgery and the ACTH stimulation test, and cumulated GC dose per weight per day. The comparisons were conducted using appropriate statistical tests such as the two-sample t-test, Welch test, or Mann–Whitney U test.
Simple logistic regression analysis was carried out to explore the relationship between the dependent variable (normal or abnormal ACTH stimulation test) and the explanatory variable (cumulated GC dose per weight per day). The analysis took into account potential non-linear relationships by including a second-degree term. Odds ratios and corresponding 95% confidence intervals were computed to quantify the strength of associations. Additionally, Cook’s distance was utilized to identify potential outliers that might have a significant impact on the regression model.
In summary, the study employed a range of statistical techniques to rigorously analyze the data and draw meaningful conclusions regarding the relationship between cumulated GC dose and HPA axis function in infants who underwent eye surgery.
Results
The study examined a cohort of 58 infants under the age of 2 years who underwent surgical procedures for congenital cataracts or glaucoma between January 2017 and December 2021. Among these, 49 infants (84.5%) underwent the ACTH stimulation test to assess HPA axis function. A few cases were excluded due to different surgical approaches or eye drop treatments.
The infants were categorized into those operated for congenital glaucoma (unilateral: n = 5, bilateral: n = 7) or congenital cataracts (unilateral: n = 20, bilateral: n = 17). Male patients accounted for 63% (31 out of 49) of the total, and some infants had systemic diseases like Stickler syndrome, Lowe syndrome, and others.
Notably, 12 infants were diagnosed with HPA axis suppression, which was more prevalent in glaucoma cases (43% in bilateral, 40% in unilateral) and bilateral cataracts (35%) compared to unilateral cataracts (5%). Among those who received subconjunctival depot dexamethasone, 43% had HPA axis suppression. Infants who underwent the ACTH stimulation test during eye drop treatment had a higher likelihood of HPA axis suppression (46%) compared to those tested after cessation (7.4%).
The median duration of HPA axis suppression was 229 days, with 67% experiencing suppression beyond 3 months. Although no Addisonian crises were recorded, three infants were hospitalized due to symptoms such as vomiting, diarrhea, and fever. Some infants with HPA axis suppression exhibited affected growth.
Several factors were associated with HPA axis suppression. Infants with suppression were younger at the time of surgery, had the ACTH test performed earlier, received a higher cumulative GC dose, and had a higher dose of GC per weight per day. A logistic regression analysis indicated that higher GC dosage per kilogram body weight per day increased the odds of HPA axis suppression.
One case involved a patient with unilateral congenital cataract who experienced intensified GC treatment due to insufficient eye drop instillation. This patient had a prolonged suppression period, more hospital admissions, increased hydrocortisone replacement dose, and growth issues.
Overall, the study highlighted the occurrence and risk factors of HPA axis suppression in infants following eye surgery for congenital cataracts or glaucoma. The findings underscore the importance of appropriate monitoring and management of GC treatments to prevent potential adverse effects on HPA axis function and growth in this vulnerable population.
Conclusion
Infants undergoing eye surgery face an elevated risk of hypothalamus–pituitary–adrenal (HPA) axis suppression, particularly as the dose of ocular glucocorticoids per weight per day increases. The study revealed a clear correlation between HPA axis suppression and several factors, including the age of the infant at the time of surgery, the duration between surgery and the ACTH stimulation test, and the cumulative dose of glucocorticoids administered.
Detecting HPA axis suppression in infants following eye surgery is crucial due to potential adverse effects on their growth, overall well-being, and the risk of Addisonian crisis. Identifying cases early can facilitate appropriate intervention, ensuring optimal growth and health outcomes for these vulnerable individuals.
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