18. pediatric eye investigator

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CLINICAL SCIENCES

Resolution of Congenital Nasolacrimal DuctObstruction With Nonsurgical Management

Pediatric Eye Disease Investigator Group*

Objective: To determine how often nasolacrimalduct obstruction (NLDO) resolves with 6 months ofnonsurgical management in infants aged 6 to less than10 months.

Methods:As part of a randomized trial evaluating thecost-effectiveness of immediate office probing vs obser-vation with deferred probing for unresolved cases, 107infants aged 6 to less than 10 months who had NLDO

and no history of nasolacrimal duct surgery were pre-scribed 6 months of nasolacrimal duct massage andtopical antibiotics as needed. Resolution of the NLDOwas assessed 6 months after study entry and was de-fined as the absence of all clinical signs of NLDO(epiphora, increased tear lake, or mucous discharge)and not having undergone NLDO surgery. Exploratoryanalyses assessed whether baseline characteristics, in-cluding age, sex, laterality, and prior treatment, were

associated with the probability of NLDO resolvingwithout surgery.

Results:At the 6-month examination, which was com-pleted for 117 of the 133 eyes (88%), the NLDO had re-solved without surgery in 77 eyes (66% [95% CI, 56%-74%]). None of the baseline characteristics we evaluatedwere 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 6monthswith nonsurgical management. Knowledge of therate of NLDO resolution in infancy without surgery willhelp clinicians and parents effectively discuss treatmentoptions.

Trial Registration: clinicaltrial.gov Identifier:NCT00780741

Arch Ophthalmol. 2012;130(6):730-734

NASOLACRIMAL DUCT OB-struction (NLDO) is acommon ocular condi-tion in infants. The re-ported rate ofNLDOreso-

lution without surgery rangesfrom 32% to95% by13 monthsof age.1-5 However, mostof the studies are retrospective, have poorfollow-up, and/or include cases of resolu-tion within the first few months of life. Be-cause surgical treatment is rarely consid-ered before 6 months of age, knowing howoften NLDO resolveswithout surgery in pa-tients with symptoms persisting beyond 6months of age is of clinical interest.

We recently conducted a multicenterrandomized trial comparing the cost-effectiveness of the following 2 ap-proaches for treating children with NLDOsymptoms persisting past 6 monthsof age:(1) immediate probing in an office set-ting and (2) 6 months of nonsurgical man-

agement followed by deferred probing un-der generalanesthesiafor unresolvedcases.Herein we report the frequency of reso-lution without surgery in 133 eyes of 107childrenaged6 to less than 10 months whowere prescribed 6 months of lacrimal sacmassage and topical antibiotics as neededfor the treatment of NLDO.

METHODS

This randomized trial was conducted by thePediatric Eye Disease Investigator Group(PEDIG) at 22 academic and community-based ophthalmology practices. The proto-col and informed consent forms compliant

with the Health Information Portability andAccountability Act of 1996 were approvedby the respective institutional review boards.The parent or guardian of each study patientgave written informed consent. The protocolis available on the PEDIG website (http://www.pedig.net, accessed October 25, 2011). Hereinwe summarize the eligibility criteria for thetrial and the protocol for the group assignedto 6 months of observation/nonsurgical man-agement followed by deferred probing ifneeded.

CME available online atwww.jamaarchivescme.comand questions on page 676

*Authors/Group Information:The members of the WritingCommittee and Pediatric EyeDisease Investigator Group arelisted at the end of this article.

ARCH OPHTHALMOL/ VOL 130 (NO. 6), JUNE 2012 WWW.ARCHOPHTHALMOL.COM730

2012 American Medical Association. All rights reserved.

wnloaded From: http://archopht.jamanetwork.com/ by Ramos SIahaan on 04/21/2015


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Major eligibility criteria for the randomizedtrial included age6 to less than 10 months, onset of NLDO symptoms before 6months of age, presence of at least 1 sign of NLDO (epiphora,increased tear lake, and/or mucopurulent discharge in the ab-sence of an upper respiratory tract infection, ocular surface irri-tation,or glaucoma), andno prior nasolacrimal duct surgery, in-cluding simple probing,nasolacrimal intubation, balloon catheterdilation, or dacryocystorhinostomy. Prior NLDO treatment con-sisting of nasolacrimal sac massage, topical antibiotics or corti-costeroids, or systemic antibiotics was permitted. Children withDown syndrome or craniofacial anomalies were excluded.

Children assigned to the observation/deferred facility prob-ing group were prescribed 6 months of nonsurgical manage-ment consisting of twice-dailylacrimal sac massage (gentle in-ward pressure applied to the lacrimal sac for 2-3 seconds) to

be performedwhen discharge waspresent, andantibiotic dropssupplied at randomization (investigator choice of tobramycinsulfate, 0.3%, or moxifloxacin hydrochloride, 0.5%) were to beused (1 drop 4 times a day) when discharge was purulent.Per protocol, surgery wasnot to be performedbeforethe comple-tion of 6 months of follow-up. A telephone contact was made3 months (2 weeks) after randomization to inquire whethersymptoms were still present. Follow-up examinations to as-sess for the presence of epiphora, increased tear lake, and/ormucous discharge were performed 6 months (2 weeks) afterenrollment and at 18 months of age (4 weeks). Patients whohad 1 or more clinical signs of NLDO at the 6-month visit (oc-curring at ages 12 to 16 months) were to undergo a nasolac-rimal duct probing procedure under general anesthesia in a sur-gical facility within 4 weeks.

Resolutionwas defined as the absence of clinical signs ofNLDO (epiphora, increased tear lake, or mucous discharge) onclinical examination and not having undergone NLDO sur-gery. The proportion of eyes with resolution of NLDO with-outsurgeryafter6 months of observation andnonsurgical man-agement anda 95% CI were calculated using logistic regressionwith generalized estimating equations to adjust for the corre-lation between eyes of patients with bilateral NLDO.6 The pri-maryanalysisincluded onlypatientswho completedthe 6-monthvisit. For a secondary analysis including all patients, multipleimputations with the logistic regression method7 were used toimpute a 6-month outcome based on 3-month data for 15 pa-

tientswho missedthe 6-month visit.The associationsof 6-monthresolution without surgery, and baseline demographic and clini-cal characteristics were assessed by estimatingrelative risksusingPoisson regression8 and using generalized estimating equa-tions to adjustfor the correlation between eyes of patients withbilateral NLDO.6

All analyses were conducted using commercially availablestatistical software (SAS, version 9.1; SAS Institute, Inc).

RESULTS

The107patients(133eyes)whowereprescribed6monthsofnonsurgicalmanagementrangedinagefrom 6.0monthsto10.0months,withameanageof7.8months.Fifty-threepatients(50%)werefemaleand87(81%)werewhite.Eighty-onepatients(76%)hadunilateralNLDOand26(24%)hadbilateralNLDO.Onehundredfifteenofthe133eyes(87%)had been treatedwith lacrimal sac massage and/or topicalantibiotics before entering the study.

Four patients with unilateral NLDO underwent sur-gery during the 6-month nonsurgical management pe-riod: 2 in the first month and 2 in the second month. Thereasons for early surgery included parent request be-

cause of continuing or worsening symptoms (n=3) anddevelopment of cellulitis (n=1).The 3-month telephonecall was completed by the par-

ents 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 by92 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 completethe 6-month visit, 3 had undergone surgery within 6months of enrollment, 5 were symptomatic at 3 months,

Table 1. Resolution of NLDO Without Surgery

3-moTelephone

Calla

6-moPostrandomization

Visitb

Patients with unilateral NLDO,No. (%) (n = 81)

(n = 80) (n = 67)

Resolved without surgery 39 (49) 44 (66)

Patients with bilateral NLDO,No. (%) (n = 26)

(n = 26) (n = 25)

Both eyes resolved without surgery 9 (35) 14 (56)c

Only 1 eye resolved without surgery 2 (8) 5 (20)

Neither eye resolved without surgery 15 (58) 6 (24)

All eyes (n = 133) (n = 132) (n = 117)

No. resolved without surgery 59 77

Percentage (95% CI) resolvedwithout surgery

46 (37-55) 66 (56-74)

Abbreviation: NLDO, nasolacrimal duct obstruction.a Data are from parental report of presence or absence of symptoms.b Of 92 patients who completed the visit 6 months after enrollment, 88 (96%)

completed the visit within the protocol window of 22 to 28 weeks fromrandomization, 2 (2%) at 29 to 30 weeks, and 2 (2%) later than 30 weeks (1 at31 weeks and 1 at 36 weeks).

c The 95% CI is 37% to 74%.

3-moTelephone Call

6-moVisit

Eyes assignedto observation/deferred facilityprobing group

133

Resolved withoutsurgery

38

Not resolvedwithout surgery

10

Had no data8

With no symptoms56

Resolved withoutsurgery

38

Not resolvedwithout surgery

29

Had no data5

With symptoms72

Resolved without surgery1Had no data1

Underwent early surgery4

Figure.Flow of patients during 6 months of nonsurgical management. *Four

patients (4 eyes) underwent surgery during the 6-month deferral period: 2within the first 2 weeks of the study and 2 about 2 months into the study. Thereasons for the early surgery included parent request because of continuing orworsening symptoms (n=3) and development of cellulitis (n=1).





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and 8 were not symptomatic at 3 months (Figure).Among the25 patients who had bilateral NLDO, 14 (56%[95% CI, 37%-74%]) had resolution in both eyes with-out surgery at 6 months.

The secondary analysis using multiple imputation forthe eyes of patients who missed the 6-month visit yieldedsimilar results (probability of nonsurgical resolution inan eye, 64% [95% CI, 54%-73%]).

Baseline demographic and clinical characteristics, in-cluding age, sex, laterality, and prior treatment, were notfound to be associated with 6-month resolution withoutsurgery (Table 2).

Of the 77 eyes that showed no signs of NLDO at the6-month postenrollment visit, an additional examina-tion was performed at approximately 18 months of age(1-4 months after the 6-month visit, depending on thepatients age at study enrollment); 63 eyes (82%) had nosigns of NLDO, 12 (16%) had clinical signs of NLDO,and 2 (3%) had undergone surgery.

COMMENT

As part of a randomized treatment trial of 2 approachesfor treating NLDO, we assessed how often the conditionresolves with nonsurgical management in infants withsymptoms at 6 to less than 10 months of age, the agerange at which nasolacrimal duct probing in an office

setting is considered feasible. We found that duringthe 6-month period of observation with lacrimal sacmassage and topical antibiotics used as needed, abouthalf the eyes were reported by parents to be asymp-tomatic at 3 months and about two-thirds of eyes werefree of signs of NLDO at a clinical assessment at 6months.

Although several studies in the literature report ratesof NLDOresolution with nonsurgical management,1-5 weare aware of only one that specifically reports resolutionin patients with symptoms persisting past 6 months of

Table 2. Six-Month Resolution of Nasolacrimal Duct Obstruction Without Surgery Accordingto Baseline Demographic and Clinical Characteristics

Baseline Characteristic No. of Eyes

6-mo Resolution Without Surgery

No. (%)a RR (95% CI) b

Total 117 77 (66)

Age at enrollment, mo

6 to 7 45 31 (69) 1 [Reference]

7 to 8 31 21 (68) 1.02 (0.73-1.43)

8 to 9 20 11 (55) 0.82 (0.52-1.30)

9 to 10c 21 14 (67) 0.96 (0.64-1.45)

Sex

Female 55 36 (65) 0.99 (0.75-1.32)

Male 62 41 (66) 1 [Reference]

Race/ethnicity

White 96 62 (65) 0.85 (0.63-1.14)

Nonwhite 21 15 (71) 1 [Reference]

Laterality

Unilateral 67 44 (66) 1 [Reference]

Bilateral 50 33 (66) 1.01 (0.74-1.36)

Epiphora

Present 93 61 (66) 1.15 (0.75-1.75)

Absent 24 16 (67) 1 [Reference]

Mucous discharge

Present 86 55 (64) 1.04 (0.76-1.43)

Absent 31 22 (71) 1 [Reference]Increased tear lake

Present 113 74 (65) 0.93 (0.75-1.15)

Absent 4 3 (75) 1 [Reference]

No. of clinical signs d

1 17 14 (82) 1.13 (0.82-1.54)

2 or 3 100 63 (63) 1 [Reference]

Prior treatmente

Nasolacrimal sac massage and antibiotics 58 35 (60) 1.07 (0.66-1.74)

Nasolacrimal sac massage only 23 16 (70) 1.22 (0.71-2.09)

Antibiotics only 21 17 (81) 1.33 (0.81-2.18)

None 14 8 (57) 1 [Reference]

Abbreviation: RR, relative risk.a Proportions are directly calculated and are not corrected for correlation of eyes in patients with both eyes in the study.b Refers to a comparison of risk of resolution without surgery between the specified level vs the reference level. Relative risks and 95% CIs are calculated from

Poisson regression models using the factor of interest as the only covariate. All models used generalized estimating equations6 to account for the intereyecorrelation between eyes from bilateral cases.

c One 10-month-old patient was technically ineligible but was included in the analysis.d Included epiphora, mucous discharge, and increased tear l ake.e Prior treatment status was unknown for 1 eye.





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age. In a prospective study of infants with symptoms per-sisting to 6 months of age, Paul4 reported that 70% of eyes(26 of 37) resolved with conservative treatment by 12months of age, a proportion that would correspond to a95% CI of 55% to 85%. Our finding of 66% (95% CI, 56%-74%), obtained from a larger sample size, is consistentwith this previous finding.4

None of the baseline characteristics we evaluatedage, sex, laterality, specific clinical signs of NLDO, and

prior treatmentwere found to be associated with reso-lution of nasolacrimal duct obstruction without sur-gery. These subanalyses can only be considered explor-atory because our small sample size limited our abilityto detect an association unless it was very strong.

Nearly 20% of eyes in which NLDO appeared to haveresolved after 6 months of nonsurgical managementshowed signs of NLDO when reassessed 1 to 4 monthslater at 18 months of age. It is possible that symptomsand signs of NLDO are intermittent and that, despite ap-pearing clear of signs on a given day, some eyes mighthave NLDO that would require surgery. Another possi-bility is that NLDO signs observed at a given visit mightbe produced or exacerbated by wind, direct sunlight, or

the presence of an upper respiratory tract illness.The strengths of this study include its prospective de-

sign and a standardized period of follow-up; however,several factors should be considered when interpretingour results. First, our rate of patient retention was lowerthan expected. Second, although our estimate of an eyesprobability of 6-month resolution without surgery is moreprecise than those from previous studies, the confi-dence interval is still fairly wide. Third, because pa-tients with bilateral NLDO would still require surgery ifNLDO resolves in only 1 eye, how often NLDO resolvesin both eyes in 6 months without surgery may be of greaterinterest. Although we observed thisproportion to be 56%(Table 1), we cannot draw a definitive conclusion be-cause the confidence interval is very wide (37%-74%) be-causeof thesmall number of patientswith bilateral NLDO.Fourth, potential misclassification of outcome can oc-cur based on the presence or absence of signs at a singleoutcome visit. Fifth, the frequency and type of the non-surgical treatment might potentially affect the resolu-tion rate. The study did not assess compliance with lac-rimal massage or antibiotics; therefore, we cannot assesswhether potential lack of adherence may have loweredthe resolution rate we observed. It is also possible thatour rate of resolution might have been higher had thelacrimal massage regimen been more intensive, been spe-cifically demonstrated to parents, or used the Crigler hy-

drostatic method,9

which has been shown to be more ef-fective than simple massage.10 Finally, without a controlgroup, we cannot determine to what extent resolutionwas related to the lacrimal massage, antibiotics, or thepassage of time.

Knowing that more than half the NLDO cases in in-fants aged 6 to less than 10 months will resolve within 6months with nonsurgical management is an importantcomponent in comparing early vs deferred surgical treat-ment approaches and should help clinicians and par-ents more effectively discuss treatment options.

Submitted for Publication: November 11, 2011; final re-vision received January 19, 2012; accepted January 30,2012.Correspondence:David B. Petersen, MD, c/o Jaeb Cen-ter for Health Research, 15310 Amberly Dr, Ste 350,Tampa, FL 33647 ([email protected]).The Pediatric Eye Disease Investigator GroupLead Authors/Writing Committee: The following individu-als take authorship responsibility for the results: David

B. Petersen, MD; Danielle L. Chandler, MSPH; MichaelX. Repka, MD, MBA. Additional writing committee mem-bers (alphabetical): Roy W. Beck, MD, PhD; Eric R.Crouch III, MD; Katherine A. Lee, MD, PhD; MicheleMelia, ScM; David G. Morrison, MD; FarukH. Orge, MD;Benjamin H. Ticho, MD.Clinicalsites thatparticipated in thisprotocol: Sites are listedin order by number of patients enrolled into the study.Personnel are listed as (I) for Investigator (C) for Coor-dinator, and (E) for Examiner.Pediatric Ophthalmologyof Erie, Erie PA:Nicholas A. Sala (I); Rhonda M. Hodde(C); Veda L. Zeto (C). St. Lukes Childrens Ophthalmol-ogy, Boise, ID:Katherine A. Lee (I); Bonita R. Schwein-ler (C); Larry W. Plum (E). Rocky Mountain Eye Care As-

sociates, Salt Lake City, UT: David B. Petersen (I); J. RyanMcMurtrey (C).Pediatric Ophthalmology and Strabis-mus Associates, Providence, RI:David Robbins Tien (I);Gi H. Yoon-Huang (I); Myra B. McGuinness (C); JessicaM. De La Rosa (C); ColleenM. Bailey (E); Jo AnnMarinaro(E).The Eye Specialists Center, LLC, Chicago Ridge, IL:Benjamin H. Ticho (I); Alexander J. Khammar (I); Debo-rah A. Clausius (C); James B. Coletta (C); Barbara C. Im-ler (E). Pediatric Ophthalmology Associates, Inc at Nation-wide Childrens Hospital, Columbus, OH*: Don L. Bremer(I); Cybil M. Cassady (I); Richard P. Golden (I); MaryLou McGregor (I); David L. Rogers (I); Gary L. Rogers(I); Rae R. Fellows (C); Meghan C. McMillin (C); Te-resa M. Rinehart (C); Amy J. Wagner (C); Jenny A. Bren-

dez (E); Rich E. Cox (E). Childrens Medical Center, Dal-las, 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); Gay-lord G. Ventura (C).Vanderbilt Eye Center, Nashville,TN**:David G. Morrison (I); Lisa A. Fraine (C); Ron-ald J. Biernacki (E); Christine C. Franklin (E); Kelsie J.Haskins (E).Everett and Hurite Ophthalmic Association,Cranberry Township, PA: Darren L. Hoover (I); PamelaA. 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); NatarioL. Couser (E). Concord Eye Care PC, Concord, NH: Chris-tie L. Morse (I); Caroline C. Fang (C); Melanie L. Chris-

tian (C); VirginiaX. Karlsson (E). ColeEye Institute,Cleve-land, 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). Uni-versity of Minnesota, Minneapolis, MN**: C. Gail Sum-mers (I); Erick D. Bothun (I); Inge De Becker (I); AnnM. 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); SuzanneS. LaRiviere (E).Family & Childrens Eye Center of New





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Mexico, Albuquerque, NM: Todd A. Goldblum (I); An-gela Alfaro (C).St. Johns ClinicEye Specialists, Spring-field, MO: Scott Atkinson (I); Crystal L. Trythall (C); An-gela B. Hendrickson (E). Ophthalmology Associates ofGreater Annapolis, Arnold, MD:John M. Avallone (I); Char-lene R. Bryant (C); Wanda E. Peyton (E).Department ofOphthalmology, Rainbow Babies & Childrens Hospital,Cleveland, OH: Faruk H. Orge (I); Sara E. Schoeck (I);Beth J. Colon (C); Nina X. Mar (C); Reena S. Vaswani

(E).DAmbrosio Eye Care, Lancaster, MA: Oren L. Weis-berg (I); Shannon M. Giansanti (C); Julie M. Kaddy (C).*Center received support used for this project from anunrestricted grant support from the Ohio Lions Eye Re-search Foundation, Bellville, Ohio.**Center received support used for this project from anunrestricted grant fromResearchto Prevent Blindness Inc,New York, New York.PEDIG Coordinating Center: Raymond T. Kraker, RoyW.Beck, Christina M. Cagnina-Morales, Danielle L. Chan-dler, 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, KatherineA. Lee, Jonathan M. Holmes, Danielle L. Chandler, KevinFrick,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, Don-ald F. Everett, Veda Lori Zeto, Rae Fellows, and all par-ticipating investigators.PEDIG Executive Committee (dates listed for members oncommittee for part of study):Jonathan M. Holmes (chair),Roy W. Beck, Eileen E. Birch, Donald F. Everett, Ray-mond T. Kraker, Michael X. Repka, Susan A. Cotter, Da-vidK. Wallace, David B. Petersen (2010 to present),Laura

Enyedi (2011 to present), Darren L. Hoover (2008, 2011to present), David L. Rogers (2011 to present), Aaron M.Miller (2011 to present), Jorie L. Jackson (2011 to pres-ent), 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 Hus-ton (2008-2009), Katherine A. Lee (2008-2009), NoelleS. Matta (2008-2009), David Morrison (2008-2009),Mitchell Scheiman (2008).PEDIG Data and Safety Monitoring Committee (dates listedfor members on committee for part of study): Marie Diener-West (chair), John D. Baker, Barry Davis, Velma Dob-son (2008-2010), Donald F. Everett, Dale L. Phelps, Ste-phen Poff, Richard A. Saunders, Lawrence Tychsen.

Financial Disclosure:None reported.Funding/Support:This study was supported by grantsEY011751 and EY018810 from the National Eye Insti-tute, National Institutes of Health, Department of Healthand Human Services. Alcon Laboratories, Inc, providedantibiotic eyedrops and antibiotic/corticosteroid eye-drops at no cost to the study. The sole purpose was tostandardize the drugs used in study;no comparisons weremade between drugs.Disclaimer: The funding organization approved the pro-tocol but had no role in the conduct of the study; in thecollection, management, analysis, and interpretation ofthe data; or in the preparation, review, and approval ofthe manuscript.

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