Figure. Flow of patients during 6 months of nonsurgical management. *Four patients (4 eyes) underwent surgery during the 6-month deferral period: 2 within the first 2 weeks of the study and 2 about 2 months into the study. The reasons for the early surgery included parent request because of continuing or worsening symptoms (n = 3) and development of cellulitis (n = 1).
Pediatric Eye Disease Investigator Group* . Resolution of Congenital Nasolacrimal Duct Obstruction With Nonsurgical Management. Arch Ophthalmol. 2012;130(6):730-734. doi:10.1001/archophthalmol.2012.454
* Authors/Group Information: The members of the Writing Committee and Pediatric Eye Disease Investigator Group are listed below.
Objective To determine how often nasolacrimal duct obstruction (NLDO) resolves with 6 months of nonsurgical management in infants aged 6 to less than 10 months.
Methods As part of a randomized trial evaluating the cost-effectiveness of immediate office probing vs observation with deferred probing for unresolved cases, 107 infants aged 6 to less than 10 months who had NLDO and no history of nasolacrimal duct surgery were prescribed 6 months of nasolacrimal duct massage and topical antibiotics as needed. Resolution of the NLDO was assessed 6 months after study entry and was defined as the absence of all clinical signs of NLDO (epiphora, increased tear lake, or mucous discharge) and not having undergone NLDO surgery. Exploratory analyses assessed whether baseline characteristics, including age, sex, laterality, and prior treatment, wereassociated with the probability of NLDO resolving without surgery.
Results At the 6-month examination, which was completed for 117 of the 133 eyes (88%), the NLDO had resolved without surgery in 77 eyes (66% [95% CI, 56%-74%]). None of the baseline characteristics we evaluated were found to be associated with resolution.
Conclusions In infants 6 to less than 10 months of age, more than half of eyes with NLDO will resolve within 6 months with nonsurgical management. Knowledge of the rate of NLDO resolution in infancy without surgery will help clinicians and parents effectively discuss treatment options.
Trial Registration clinicaltrial.gov Identifier: NCT00780741
Quiz Ref IDNasolacrimal duct obstruction (NLDO) is a common ocular condition in infants. The reported rate of NLDO resolution without surgery ranges from 32% to 95% by 13 months of age.1- 5 However, most of the studies are retrospective, have poor follow-up, and/or include cases of resolution within the first few months of life. Because surgical treatment is rarely considered before 6 months of age, knowing how often NLDO resolves without surgery in patients with symptoms persisting beyond 6 months of age is of clinical interest.
We recently conducted a multicenter randomized trial comparing the cost-effectiveness of the following 2 approaches for treating children with NLDO symptoms persisting past 6 months of age: (1) immediate probing in an office setting and (2) 6 months of nonsurgical management followed by deferred probing under general anesthesia for unresolved cases. Herein we report the frequency of resolution without surgery in 133 eyes of 107 children aged 6 to less than 10 months who were prescribed 6 months of lacrimal sac massage and topical antibiotics as needed for the treatment of NLDO.
This randomized trial was conducted by the Pediatric Eye Disease Investigator Group (PEDIG) at 22 academic and community-based ophthalmology practices. The protocol and informed consent forms compliant with the Health Information Portability and Accountability Act of 1996 were approved by the respective institutional review boards. The parent or guardian of each study patient gave written informed consent. The protocol is available on the PEDIG website (http://www.pedig.net, accessed October 25, 2011). Herein we summarize the eligibility criteria for the trial and the protocol for the group assigned to 6 months of observation/nonsurgical management followed by deferred probing if needed.
Major eligibility criteria for the randomized trial included age 6 to less than 10 months, onset of NLDO symptoms before 6 months of age, presence of at least 1 sign of NLDO (epiphora, increased tear lake, and/or mucopurulent discharge in the absence of an upper respiratory tract infection, ocular surface irritation, or glaucoma), and no prior nasolacrimal duct surgery, including simple probing, nasolacrimal intubation, balloon catheter dilation, or dacryocystorhinostomy. Prior NLDO treatment consisting of nasolacrimal sac massage, topical antibiotics or corticosteroids, or systemic antibiotics was permitted. Children with Down syndrome or craniofacial anomalies were excluded.
Children assigned to the observation/deferred facility probing group were prescribed 6 months of nonsurgical management consisting of twice-daily lacrimal sac massage (gentle inward pressure applied to the lacrimal sac for 2-3 seconds) to be performed when discharge was present, and antibiotic drops supplied at randomization (investigator choice of tobramycin sulfate, 0.3%, or moxifloxacin hydrochloride, 0.5%) were to be used (1 drop ≤4 times a day) when discharge was purulent. Per protocol, surgery was not to be performed before the completion of 6 months of follow-up. A telephone contact was made 3 months (±2 weeks) after randomization to inquire whether symptoms were still present. Follow-up examinations to assess for the presence of epiphora, increased tear lake, and/or mucous discharge were performed 6 months (±2 weeks) after enrollment and at 18 months of age (±4 weeks). Patients who had 1 or more clinical signs of NLDO at the 6-month visit (occurring at ages 12 to <16 months) were to undergo a nasolacrimal duct probing procedure under general anesthesia in a surgical facility within 4 weeks.
Resolution was defined as the absence of clinical signs of NLDO (epiphora, increased tear lake, or mucous discharge) on clinical examination and not having undergone NLDO surgery. The proportion of eyes with resolution of NLDO without surgery after 6 months of observation and nonsurgical management and a 95% CI were calculated using logistic regression with generalized estimating equations to adjust for the correlation between eyes of patients with bilateral NLDO.6 The primary analysis included only patients who completed the 6-month visit. For a secondary analysis including all patients, multiple imputations with the logistic regression method7 were used to impute a 6-month outcome based on 3-month data for 15 patients who missed the 6-month visit. The associations of 6-month resolution without surgery, and baseline demographic and clinical characteristics were assessed by estimating relative risks using Poisson regression8 and using generalized estimating equations to adjust for the correlation between eyes of patients with bilateral NLDO.6
All analyses were conducted using commercially available statistical software (SAS, version 9.1; SAS Institute, Inc).
The 107 patients (133 eyes) who were prescribed 6 months of nonsurgical management ranged in age from 6.0 months to 10.0 months, with a mean age of 7.8 months. Fifty-three patients (50%) were female and 87 (81%) were white. Eighty-one patients (76%) had unilateral NLDO and 26 (24%) had bilateral NLDO. One hundred fifteen of the 133 eyes (87%) had been treated with lacrimal sac massage and/or topical antibiotics before entering the study.
Four patients with unilateral NLDO underwent surgery during the 6-month nonsurgical management period: 2 in the first month and 2 in the second month. The reasons for early surgery included parent request because of continuing or worsening symptoms (n = 3) and development of cellulitis (n = 1).
The 3-month telephone call was completed by the parents of 106 patients (99%). Fifty-nine of 132 eyes (46% [95% CI, 37%-55%]) were reported to be asymptomatic.
At the visit 6 months after enrollment, completed by 92 patients (86%), NLDO in 77 of 117 eyes (66% [95% CI, 56%-74%]) had resolved without surgery (Table 1). Of the 16 eyes of the 15 patients who did not complete the 6-month visit, 3 had undergone surgery within 6 months of enrollment, 5 were symptomatic at 3 months, and 8 were not symptomatic at 3 months (Figure). Among the 25 patients who had bilateral NLDO, 14 (56% [95% CI, 37%-74%]) had resolution in both eyes without surgery at 6 months.
The secondary analysis using multiple imputation for the eyes of patients who missed the 6-month visit yielded similar results (probability of nonsurgical resolution in an eye, 64% [95% CI, 54%-73%]).
Baseline demographic and clinical characteristics, including age, sex, laterality, and prior treatment, were not found to be associated with 6-month resolution without surgery (Table 2).
Quiz Ref IDOf the 77 eyes that showed no signs of NLDO at the 6-month postenrollment visit, an additional examination was performed at approximately 18 months of age (1-4 months after the 6-month visit, depending on the patient's age at study enrollment); 63 eyes (82%) had no signs of NLDO, 12 (16%) had clinical signs of NLDO, and 2 (3%) had undergone surgery.
As part of a randomized treatment trial of 2 approaches for treating NLDO, we assessed how often the condition resolves with nonsurgical management in infants with symptoms at 6 to less than 10 months of age, the age range at which nasolacrimal duct probing in an office setting is considered feasible. Quiz Ref IDWe found that during the 6-month period of observation with lacrimal sac massage and topical antibiotics used as needed, about half the eyes were reported by parents to be asymptomatic at 3 months and about two-thirds of eyes were free of signs of NLDO at a clinical assessment at 6 months.
Although several studies in the literature report rates of NLDO resolution with nonsurgical management,1- 5 we are aware of only one that specifically reports resolution in patients with symptoms persisting past 6 months of age. In a prospective study of infants with symptoms persisting to 6 months of age, Paul4 reported that 70% of eyes (26 of 37) resolved with conservative treatment by 12 months of age, a proportion that would correspond to a 95% CI of 55% to 85%. Our finding of 66% (95% CI, 56%-74%), obtained from a larger sample size, is consistent with this previous finding.4
None of the baseline characteristics we evaluated—age, sex, laterality, specific clinical signs of NLDO, and prior treatment—were found to be associated with resolution of nasolacrimal duct obstruction without surgery. These subanalyses can only be considered exploratory because our small sample size limited our ability to detect an association unless it was very strong.
Nearly 20% of eyes in which NLDO appeared to have resolved after 6 months of nonsurgical management showed signs of NLDO when reassessed 1 to 4 months later at 18 months of age. It is possible that symptoms and signs of NLDO are intermittent and that, despite appearing clear of signs on a given day, some eyes might have NLDO that would require surgery. Another possibility is that NLDO signs observed at a given visit might be produced or exacerbated by wind, direct sunlight, or the presence of an upper respiratory tract illness.
Quiz Ref IDThe strengths of this study include its prospective design and a standardized period of follow-up; however, several factors should be considered when interpreting our results. Quiz Ref IDFirst, our rate of patient retention was lower than expected. Second, although our estimate of an eye's probability of 6-month resolution without surgery is more precise than those from previous studies, the confidence interval is still fairly wide. Third, because patients with bilateral NLDO would still require surgery if NLDO resolves in only 1 eye, how often NLDO resolves in both eyes in 6 months without surgery may be of greater interest. Although we observed this proportion to be 56% (Table 1), we cannot draw a definitive conclusion because the confidence interval is very wide (37%-74%) because of the small number of patients with bilateral NLDO. Fourth, potential misclassification of outcome can occur based on the presence or absence of signs at a single outcome visit. Fifth, the frequency and type of the nonsurgical treatment might potentially affect the resolution rate. The study did not assess compliance with lacrimal massage or antibiotics; therefore, we cannot assess whether potential lack of adherence may have lowered the resolution rate we observed. It is also possible that our rate of resolution might have been higher had the lacrimal massage regimen been more intensive, been specifically demonstrated to parents, or used the Crigler hydrostatic method,9 which has been shown to be more effective than simple massage.10 Finally, without a control group, we cannot determine to what extent resolution was related to the lacrimal massage, antibiotics, or the passage of time.
Knowing that more than half the NLDO cases in infants aged 6 to less than 10 months will resolve within 6 months with nonsurgical management is an important component in comparing early vs deferred surgical treatment approaches and should help clinicians and parents more effectively discuss treatment options.
Correspondence: David B. Petersen, MD, c/o Jaeb Center for Health Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647 (firstname.lastname@example.org).
Submitted for Publication: November 11, 2011; final revision received January 19, 2012; accepted January 30, 2012.
The Pediatric Eye Disease Investigator GroupLead Authors/Writing Committee: The following individuals take authorship responsibility for the results: David B. Petersen, MD; Danielle L. Chandler, MSPH; Michael X. Repka, MD, MBA. Additional writing committee members (alphabetical): Roy W. Beck, MD, PhD; Eric R. Crouch III, MD; Katherine A. Lee, MD, PhD; Michele Melia, ScM; David G. Morrison, MD; Faruk H. Orge, MD; Benjamin H. Ticho, MD.
Clinical sites that participated in this protocol: Sites are listed in order by number of patients enrolled into the study. Personnel are listed as (I) for Investigator (C) for Coordinator, and (E) for Examiner. Pediatric Ophthalmology of Erie, Erie PA: Nicholas A. Sala (I); Rhonda M. Hodde (C); Veda L. Zeto (C). St. Luke's Children's Ophthalmology, Boise, ID: Katherine A. Lee (I); Bonita R. Schweinler (C); Larry W. Plum (E). Rocky Mountain Eye Care Associates, Salt Lake City, UT: David B. Petersen (I); J. Ryan McMurtrey (C). Pediatric Ophthalmology and Strabismus Associates, Providence, RI: David Robbins Tien (I); Gi H. Yoon-Huang (I); Myra B. McGuinness (C); Jessica M. De La Rosa (C); Colleen M. Bailey (E); Jo Ann Marinaro (E). The Eye Specialists Center, LLC, Chicago Ridge, IL: Benjamin H. Ticho (I); Alexander J. Khammar (I); Deborah A. Clausius (C); James B. Coletta (C); Barbara C. Imler (E). Pediatric Ophthalmology Associates, Inc at Nationwide Children's Hospital, Columbus, OH*: Don L. Bremer (I); Cybil M. Cassady (I); Richard P. Golden (I); Mary Lou McGregor (I); David L. Rogers (I); Gary L. Rogers (I); Rae R. Fellows (C); Meghan C. McMillin (C); Teresa M. Rinehart (C); Amy J. Wagner (C); Jenny A. Brendez (E); Rich E. Cox (E). Children"s Medical Center, Dallas, TX**: David R. Weakley Jr (I); Clare L. Dias (C); Xiaowei W. Zhang (C). Eastern Virginia Medical School, Norfolk, VA: Earl R. Crouch (I); Eric R. Crouch (I); Gaylord G. Ventura (C). Vanderbilt Eye Center, Nashville, TN**: David G. Morrison (I); Lisa A. Fraine (C); Ronald J. Biernacki (E); Christine C. Franklin (E); Kelsie J. Haskins (E). Everett and Hurite Ophthalmic Association, Cranberry Township, PA: Darren L. Hoover (I); Pamela A. Huston (C). Emory University, Atlanta, GA: Scott R. Lambert (I); Amy K. Hutchinson (I); Phoebe D. Lenhart (I); Marla J. Shainberg (C); Rachel A. Robb (C); Natario L. Couser (E). Concord Eye Care PC, Concord, NH: Christie L. Morse (I); Caroline C. Fang (C); Melanie L. Christian (C); Virginia X. Karlsson (E). Cole Eye Institute, Cleveland, OH**: Elias Traboulsi (I); Paul J. Rychwalski (I); Susan W. Crowe (C). Family Eye Group, Lancaster, PA: David I. Silbert (I); Eric L. Singman (I); Noelle S. Matta (C); Garry L. Leckemby (E); Michael R. Pavlica (E). University of Minnesota, Minneapolis, MN**: C. Gail Summers (I); Erick D. Bothun (I); Inge De Becker (I); Ann M. Holleschau (C); Anna I. de Melo (E); Kathy M. Hogue (E); Kim S. Merrill (E). Houston Eye Associates, Tomball, TX: Aaron M. Miller (I); Jorie L. Jackson (C); Suzanne S. LaRiviere (E). Family & Children's Eye Center of New Mexico, Albuquerque, NM: Todd A. Goldblum (I); Angela Alfaro (C). St. John's Clinic–Eye Specialists, Springfield, MO: Scott Atkinson (I); Crystal L. Trythall (C); Angela B. Hendrickson (E). Ophthalmology Associates of Greater Annapolis, Arnold, MD: John M. Avallone (I); Charlene R. Bryant (C); Wanda E. Peyton (E). Department of Ophthalmology, Rainbow Babies & Children's Hospital, Cleveland, OH: Faruk H. Orge (I); Sara E. Schoeck (I); Beth J. Colon (C); Nina X. Mar (C); Reena S. Vaswani (E). D’Ambrosio Eye Care, Lancaster, MA: Oren L. Weisberg (I); Shannon M. Giansanti (C); Julie M. Kaddy (C).
*Center received support used for this project from an unrestricted grant support from the Ohio Lions Eye Research Foundation, Bellville, Ohio.
**Center received support used for this project from an unrestricted grant from Research to Prevent Blindness Inc, New York, New York.
PEDIG Coordinating Center: Raymond T. Kraker, Roy W. Beck, Christina M. Cagnina-Morales, Danielle L. Chandler, Laura E. Clark, Chelsea Costa, Elise R. Diamond, Quayleen Donahue, Brooke P. Fimbel, Nicole C. Foster, Elizabeth L. Lazar, Stephanie V. Lee, Lee Anne Lester, B. Michele Melia, Pamela S. Moke, Diana E. Rojas.
National Eye Institute, Bethesda, MD: Donald F. Everett.
NLD3 Planning Committee: Michael X. Repka, Katherine A. Lee, Jonathan M. Holmes, Danielle L. Chandler, Kevin Frick, David I. Silbert, Nicholas A. Sala, Darren L. Hoover, Roy W. Beck.
NLD3 Steering Committee: Katherine A. Lee, Michael X. Repka, Jonathan M. Holmes, Danielle L. Chandler, Donald F. Everett, Veda Lori Zeto, Rae Fellows, and all participating investigators.
PEDIG Executive Committee (dates listed for members on committee for part of study): Jonathan M. Holmes (chair), Roy W. Beck, Eileen E. Birch, Donald F. Everett, Raymond T. Kraker, Michael X. Repka, Susan A. Cotter, David K. Wallace, David B. Petersen (2010 to present), Laura Enyedi (2011 to present), Darren L. Hoover (2008, 2011 to present), David L. Rogers (2011 to present), Aaron M. Miller (2011 to present), Jorie L. Jackson (2011 to present), Marjean T. Kulp (2010 to present), Benjamin H. Ticho (2010 to present), Eric R. Crouch III (2010-2011), Darron Bacal (2009-2010), Robert Rutstein (2009-2010), Stephen Christiansen (2008-2010), Pamela Huston (2008-2009), Katherine A. Lee (2008-2009), Noelle S. Matta (2008-2009), David Morrison (2008-2009), Mitchell Scheiman (2008).
PEDIG Data and Safety Monitoring Committee (dates listed for members on committee for part of study): Marie Diener-West (chair), John D. Baker, Barry Davis, Velma Dobson (2008-2010), Donald F. Everett, Dale L. Phelps, Stephen Poff, Richard A. Saunders, Lawrence Tychsen.
Financial Disclosure: None reported.
Funding/Support: This study was supported by grants EY011751 and EY018810 from the National Eye Institute, National Institutes of Health, Department of Health and Human Services. Alcon Laboratories, Inc, provided antibiotic eyedrops and antibiotic/corticosteroid eyedrops at no cost to the study. The sole purpose was to standardize the drugs used in study; no comparisons were made between drugs.
Disclaimer: The funding organization approved the protocol but had no role in the conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, and approval of the manuscript.