Nasolacrimal Duct Obstruction
Conditions
Keywords
Nasolacrimal duct obstruction, Simple probing
Brief summary
The purpose of this study is: To determine the cost-effectiveness of treating NLDO using immediate office probing compared with deferred probing in a facility setting. As part of the primary objective, the study will determine the proportion of eyes experiencing spontaneous resolution among subjects randomized to the deferred probing group. The secondary objectives are: 1. To determine the success proportion for eyes undergoing immediate office probing as an initial procedure. 2. To determine the success proportion for eyes undergoing deferred facility probing as an initial procedure.
Detailed description
Nasolacrimal duct obstruction (NLDO) is a common ocular condition in the first year of life. Many cases will resolve spontaneously or with massage. Many studies of primary treatment of NLDO have been reported, however these case series have largely been retrospective, uncontrolled, and conducted in single centers. The substantial uncertainty regarding an estimate of spontaneous resolution is a primary reason for conducting the current study. Probing is the most widely-used initial treatment for NLDO in infancy. Our group recently completed a prospective observational study which found a 78% success proportion of probing among children aged 6 to \<12 months. Other estimates of the success rate for probing vary between 69% and 92%. Two differing approaches to nasolacrimal probing have been most often been used: (1) immediate office probing (early probing - generally soon after 6 months of age) and (2) medical management (episodic antibiotic eye drops with massage of the lacrimal sac) until 9-13 months of age followed by probing under general anesthesia or conscious sedation (deferred probing). The advantages of early probing are the avoidance of general anesthesia or conscious sedation, immediate resolution of symptoms, fewer physician visits, fewer antibiotic prescriptions, lesser cost per procedure, and possible prevention of fibrosis from inflammation in the nasolacrimal duct. The advantages of deferred probing include more subject comfort with the procedure and possible avoidance of a surgical procedure completely. The optimal approach to the management of NLDO in the first year of life remains uncertain. Our prospective observational data suggest a slightly reduced chance of success with immediate office probing (75% for office probing, 80% for facility probing), however, immediate office probing may be more cost-effective even if the proportion with success is lower. For a subject undergoing a single operation, immediate office probing is less expensive than deferred probing in a facility because there is no fee for anesthesia, the facility, or for medications prescribed during the pre-operative observation period. Some portion of this lower cost would be offset however by the additional cost of a second procedure if the initial office probing is not successful. Deferred facility probing is more expensive per procedure; however, the overall costs are reduced by the number of children whose NLDO spontaneously resolves while waiting to perform the procedure in a facility. The study is a randomized clinical trial which aims to determine the cost-effectiveness of treating NLDO using immediate office probing compared with deferred probing in a facility setting. As part of the primary objective, the study will determine the proportion of eyes experiencing spontaneous resolution among subjects randomized to the deferred probing group.
Interventions
PROCEDUREImmediate Office Probing
Nasolacrimal duct probing in an office setting with topical anesthesia and restraint of the infant.
PROCEDUREDeferred Facility Probing
Nasolacrimal duct probing performed under general anesthesia in a hospital outpatient surgery center or an ambulatory surgery center.
Sponsors
National Eye Institute (NEI)
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 10 Months
Healthy volunteers
No
Inclusion criteria
* Age 6 to \<10 months * Onset of NLDO symptoms and/or signs prior to 6 months chronological age in study eye(s) * Presence in study eye(s) of epiphora, increased tear film, and/or mucous discharge in the absence of an upper respiratory infection or an ocular surface irritation that investigator believes is due to NLDO * At least one open punctum present in study eye(s) A history of NLDO treatment with lacrimal massage, topical antibiotics or steroids, or systemic antibiotics is permitted.
Exclusion criteria
* History of nasolacrimal duct surgery including probing, nasolacrimal intubation, balloon catheter dilation, or dacryocystorhinostomy in study eye(s) History of trauma to the lacrimal drainage system of the study eye(s) * Glaucoma in study eye(s) * Corneal surface disease in study eye(s) * Microphthalmia in study eye(s) * Down Syndrome * Craniosynostosis * Goldenhar sequence * Clefting syndromes * Hemifacial microsomia * Midline facial anomalies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Treatment Success | 18 months of age | Absence of three clinical signs of NLDO (epiphora, increased tear lake, and mucous discharge) upon masked examination at 18 months of age. |
| Cost of Treatment | Randomization to 18 months of age | Total cost of treatment including the cost of an initial office consultation and all surgeries received (i.e. initial surgeries and reoperations) and medications prescribed for NLDO between randomization and the 18 months of age visit. Estimates of treatment costs were obtained primarily from the 2011 Medicare Fee Schedules. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Months of Symptoms of Nasolacrimal Duct Obstruction (NLDO) Between Randomization and 18 Months of Age | Randomization to 18 months of age. | Months of NLDO symptoms between randomization and 18 months of age. When resolution of NLDO occurred without surgery, the time of resolution was estimated as the midpoint between randomization and the first time point at which symptoms/signs were reported as absent (i.e. 3-month phone call, 6-month visit, or 18 months of age visit) without a subsequent report of symptoms/signs. For patients who underwent successful surgery, months of symptoms was estimated as months between randomization and the surgery. Patients who had clinical signs present at the 18 month of age visit were considered to have had symptoms present since randomization. |
| Proportion of Deferred Facility Probing Group Participants With 6-Month Resolution of NLDO Without Surgery | Randomization to 6 months | Absence of three clinical signs of NLDO (epiphora, increased tear lake, and mucous discharge) upon unmasked examination 6 months after randomization. Participants who were operated before the 6-month visit were considered treatment failures. |
| Proportion of Participants With Office Probing Success 6 Months After Randomization | Randomization to 6 months | The proportion of immediate office group participants whose office probing was successful when assessed 6 months after randomization. Office probing success was defined as absence of three clinical signs of NLDO (epiphora, increased tear lake, and mucous discharge) 6 months after randomization and no reoperation. |
Countries
United States
Participant flow
Recruitment details
Between November 2008 and September 2010, 163 participants with unilateral nasolacrimal duct obstruction (NLDO) were enrolled at 22 clinical centers. During the same period, 57 participants were recruited with bilateral nasolacrimal duct obstruction (NLDO), however, these participants are not included in the analyses reported herein.
Participants by arm
| Arm | Count |
|---|---|
| Immediate Office Probing - Participants With Unilateral NLDO Probing to be performed in the office either the same day as randomization or within two weeks. Limited to participants with unilateral nasolacrimal duct obstruction (NLDO). | 82 |
| Deferred Facility Probing - Participants With Unilateral NLDO Probing to be performed in a facility within four weeks after completion of the 26-week visit if any of the clinical signs persist. Limited to participants with unilateral nasolacrimal duct obstruction (NLDO). | 81 |
| Total | 163 |
Baseline characteristics
| Characteristic | Immediate Office Probing - Participants With Unilateral NLDO | Deferred Facility Probing - Participants With Unilateral NLDO | Total |
|---|---|---|---|
| Age, Continuous | 7.6 months STANDARD_DEVIATION 1.2 | 7.8 months STANDARD_DEVIATION 1.3 | 7.7 months STANDARD_DEVIATION 1.2 |
| Age, Customized 6 to <7 months | 25 participants | 27 participants | 52 participants |
| Age, Customized 7 to <8 months | 28 participants | 20 participants | 48 participants |
| Age, Customized 8 to <9 months | 15 participants | 13 participants | 28 participants |
| Age, Customized 9 to <10 months | 14 participants | 21 participants | 35 participants |
| Epiphora Absent | 19 participants | 11 participants | 30 participants |
| Epiphora Present | 63 participants | 70 participants | 133 participants |
| Increased tear film Absent | 3 participants | 0 participants | 3 participants |
| Increased tear film Present | 79 participants | 81 participants | 160 participants |
| Mucous discharge Absent | 22 participants | 18 participants | 40 participants |
| Mucous discharge Present | 60 participants | 63 participants | 123 participants |
| Previous treatment for NLDO Lacrimal massage and topical antibiotics | 39 participants | 36 participants | 75 participants |
| Previous treatment for NLDO Lacrimal massage only | 18 participants | 15 participants | 33 participants |
| Previous treatment for NLDO None | 15 participants | 15 participants | 30 participants |
| Previous treatment for NLDO Topical antibiotics only | 10 participants | 14 participants | 24 participants |
| Previous treatment for NLDO Unknown | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized African American | 3 participants | 6 participants | 9 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 10 participants | 7 participants | 17 participants |
| Race/Ethnicity, Customized More than one race | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 68 participants | 66 participants | 134 participants |
| Region of Enrollment United States | 82 participants | 81 participants | 163 participants |
| Sex: Female, Male Female | 32 Participants | 42 Participants | 74 Participants |
| Sex: Female, Male Male | 50 Participants | 39 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 82 | 0 / 81 |
| serious Total, serious adverse events | 0 / 82 | 0 / 81 |
Outcome results
Primary
Cost of Treatment
Total cost of treatment including the cost of an initial office consultation and all surgeries received (i.e. initial surgeries and reoperations) and medications prescribed for NLDO between randomization and the 18 months of age visit. Estimates of treatment costs were obtained primarily from the 2011 Medicare Fee Schedules.
Time frame: Randomization to 18 months of age
Population: All participants who had unilateral nasolacrimal duct obstruction at baseline and who completed the visit at 18 months of age were analyzed. The analysis followed the intent to treat principle.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Immediate Office Probing - Participants With Unilateral NLDO | Cost of Treatment | 562 US dollars |
| Deferred Facility Probing - Participants With Unilateral NLDO | Cost of Treatment | 701 US dollars |
p-value: 0.2495% CI: [-377, 94]Point estimate on mean difference
Primary
Proportion of Participants With Treatment Success
Absence of three clinical signs of NLDO (epiphora, increased tear lake, and mucous discharge) upon masked examination at 18 months of age.
Time frame: 18 months of age
Population: All participants who had unilateral nasolacrimal duct obstruction at baseline and who completed the primary outcome visit at 18 months of age were analyzed. The analysis followed the intent-to-treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Office Probing - Participants With Unilateral NLDO | Proportion of Participants With Treatment Success | 0.92 proportion of participants |
| Deferred Facility Probing - Participants With Unilateral NLDO | Proportion of Participants With Treatment Success | 0.82 proportion of participants |
p-value: 0.0995% CI: [-0.01, 0.21]Point estimate on mean difference
Secondary
Months of Symptoms of Nasolacrimal Duct Obstruction (NLDO) Between Randomization and 18 Months of Age
Months of NLDO symptoms between randomization and 18 months of age. When resolution of NLDO occurred without surgery, the time of resolution was estimated as the midpoint between randomization and the first time point at which symptoms/signs were reported as absent (i.e. 3-month phone call, 6-month visit, or 18 months of age visit) without a subsequent report of symptoms/signs. For patients who underwent successful surgery, months of symptoms was estimated as months between randomization and the surgery. Patients who had clinical signs present at the 18 month of age visit were considered to have had symptoms present since randomization.
Time frame: Randomization to 18 months of age.
Population: All participants who had unilateral nasolacrimal duct obstruction at baseline and who completed the visit at 18 months of age were analyzed. The analysis followed the intent to treat principle.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Immediate Office Probing - Participants With Unilateral NLDO | Months of Symptoms of Nasolacrimal Duct Obstruction (NLDO) Between Randomization and 18 Months of Age | 1.8 months of symptoms |
| Deferred Facility Probing - Participants With Unilateral NLDO | Months of Symptoms of Nasolacrimal Duct Obstruction (NLDO) Between Randomization and 18 Months of Age | 4.8 months of symptoms |
p-value: <0.000195% CI: [-4, -1.8]Point estimate on mean difference
Secondary
Proportion of Deferred Facility Probing Group Participants With 6-Month Resolution of NLDO Without Surgery
Absence of three clinical signs of NLDO (epiphora, increased tear lake, and mucous discharge) upon unmasked examination 6 months after randomization. Participants who were operated before the 6-month visit were considered treatment failures.
Time frame: Randomization to 6 months
Population: All participants who had unilateral nasolacrimal duct obstruction at baseline, who were randomized to the deferred facility probing group, and who completed the 6-month visit (timed from randomization). The analysis followed the intent to treat principle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Office Probing - Participants With Unilateral NLDO | Proportion of Deferred Facility Probing Group Participants With 6-Month Resolution of NLDO Without Surgery | 0.66 proportion of participants |
Secondary
Proportion of Participants With Office Probing Success 6 Months After Randomization
The proportion of immediate office group participants whose office probing was successful when assessed 6 months after randomization. Office probing success was defined as absence of three clinical signs of NLDO (epiphora, increased tear lake, and mucous discharge) 6 months after randomization and no reoperation.
Time frame: Randomization to 6 months
Population: Participants randomized to immediate office probing who underwent office probing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immediate Office Probing - Participants With Unilateral NLDO | Proportion of Participants With Office Probing Success 6 Months After Randomization | 0.83 proportion with treatment success |