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Jurnal 4 PDF
Tear Film, Lacrimal Drainage System, and Eyelid Findings in Subjects with
Anophthalmic Socket Discharge
Mohsen Bahmani Kashkouli, M.D., Roya Zolfaghari, M.D., Acieh Es’haghi, M.D.,
Anahita Amirsardari, M.D., Mohammad Bagher Abtahi, M.D., Nasser Karimi, M.D.,
Amirpooya Alemzadeh, M.D., Mohamadreza Aghamirsalim, M.D.
PII: S0002-9394(16)30066-6
DOI: 10.1016/j.ajo.2016.02.016
Reference: AJOPHT 9631
Please cite this article as: Kashkouli MB, Zolfaghari R, Es’haghi A, Amirsardari A, Abtahi MB, Karimi N,
Alemzadeh A, Aghamirsalim M, Tear Film, Lacrimal Drainage System, and Eyelid Findings in Subjects
with Anophthalmic Socket Discharge, American Journal of Ophthalmology (2016), doi: 10.1016/
j.ajo.2016.02.016.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
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Abstract
Purpose: To compare the results of tear film and lacrimal drainage system tests between
anophthalmic socket and normal eye and assess discharge characteristics and frequency of
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prosthesis removal (questionnaire), eyelid function, and meibomian glad dysfunction (MGD).
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Method: Subjects (≥ 6 years and ≥ 6 months of wearing prosthesis) with unilateral acquired
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anophthalmic socket discharge were included. Excluded was ocular adnexal abnormality of any
reason and incomplete tests. The subjective questionnaire was completed. Blinking rate,
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lagophthalmos, eyelid laxity, MGD, Schirmer test, tear meniscus height , and dye disappearance
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test were assessed by a masked examiner. Another masked examiner performed irrigation test 1
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week later and interpreted the scintigraphy images at the end of the study.
Results: Included were 50 subjects (mean age: 31.3 years, mean prosthesis wearing: 96.1
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months). Discharge was frequent or very frequent in 85%, mucoid or mucopurulent in 90%, and
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moderate to severe in 86% of the subjects. MGD in 58%, lagophthalmos in 80%, and eyelid
laxity in 46% were observed. Anophthalmic socket sides showed a significantly lower tear
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production and higher tear drainage obstruction. Subjects with frequent prosthesis removal had a
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significantly (P=0.02) more lagophthalmos and blinking rate (P=0.04). The blinking rate was
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Conclusion: Tear film impairment (aqueous and lipid) and lacrimal drainage obstruction should
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Authors’ Degree and Affiliation: M.D., Eye Research Center, Rassoul Akram Hospital, Iran
University of Medical Sciences.
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• Short title: Anophthalmic Socket Discharge
• Corresponding author: Mohsen Bahmani Kashkouli, M.D., Eye Research Center, Rassoul
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Akram Hospital, Sattarkhan-Niayesh St., Tehran 14455-364, Iran. Phone +9821
66509162, Fax: +9821 66558811
Email: mkashkouli2@gmail.com
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Introduction
Discharge is the second concern after the health of normal eye affecting 93% of subjects with
anophthalmic socket which has different characteristics. 1-8 Jang et al. 9 reported a significantly
high rate of meibomian gland dysfunction (MGD) in the anophthalmic sockets. Severe dryness
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of the socket because of diminished tear production (impaired Schirmer test) may occur in up to
75% of anophthalmic sockets. 10,11 Little data exists regarding tear film and lacrimal drainage
system findings in the setting of an ocular prosthesis. 12 Furthermore, unrecognized lacrimal
drainage system obstruction in anophthalmic socket has been reported to presumably cause
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chronic discharge and contracted socket in a case report. 13
In the absence of a structural cause for anophthalmic socket discharge (implant exposure and
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infection, conjunctival cyst and granuloma, peg, etc.), the prosthesis itself (improper fitting,
handling, hygiene, deposits, roughness of the surface) and/ or ocular adnexa (change in the
conjunctival epithelium, impaired eyelid functions, impaired tear production and lacrimal
drainage system) may play a role in producing the discharge.
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We sought to correlate ocular adnexal findings (eyelid laxity, lagophthalmos, blinking rate,
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meibomian glad function, tear production, and lacrimal drainage system patency) and prosthesis
handling with the presence, frequency and type of anophthalmic socket discharge.
Materials and Methods
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This prospective masked case-control study was approved by the ethic committee of Iran
University Eye Research Center (21471/124/01/92) and in line with tenets of the Declaration of
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and normal eyes of 15 subjects to calculate the sample size of the study. Mean Schirmer test was
5.2 mm (SD= 1.3) on the anophthalmic socket and 11.5 (SD= 1.1) on the normal side. To find a
20% difference (α =5%, power= 90%), the sample was 22 subjects (22 cases and 22 controls).
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Lacrimal drainage diagnostic probing and irrigation showed an obstruction (partial or complete
at different levels) in 13.3% of the normal side and 66.7% of anophthalmic socket side. To find a
20% difference (α =5%, power= 90%), the sample size was 34 subjects (34 cases and 34
controls). They were not included in the main study.
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Subjects with anophthalmic socket discharge (≥ 6 years of age for feasibility of performing the
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tests) who were wearing prosthesis for more than 6 months and being under periodic care of their
ocularists were consecutively included between 1st of March 2013 to 1st of February 2014.
Excluded were improper prosthesis (displaced, extruding or rotating on rubbing the eyelids, large
or small size, rough surface), socket complications (socket contraction, anophthalmic socket
syndrome, pyogenic granuloma, inclusion cyst, presence of peg, implant exposure, infection),
using any regular drop except for artificial tear, and any systemic disease, surgery or trauma
affecting the ocular adnexal structures. Subjects with symptom of watery or dry eye on the
normal side were also excluded.
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A discharge characteristics questionnaire was completed by the subjects under supervision of the
first examiner (RZ) on the first visit. After recording the demographics, type of eye removal
procedure, and time of prosthetic fitting; blinking rate at rest, lagophthalmos, lower eyelid laxity,
MGD, upper eyelid palpebral conjunctiva, Schirmer test, tear meniscus height, lacrimal sac
regurgitation test, and 5-minute Flourscein dye disappearance test were assessed and a lacrimal
scintigraphy was requested by the first masked examiner (first visit). The second masked
examiner (MBK) assessed the puncti and performed a diagnostic lacrimal probing and irrigation
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test 1 week later (second visit) when the scintigraphy image print-outs were filed by the
secretary. The scintigraphy images were then interpreted by the second examiner without
knowing the side of anophthalmic socket at the end of the study.
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The questionnaire was a modification of Pine’s5 questionnaire. Since our subjects reported that
the “viscosity” has the same answer as “color” question and many participants did not answer the
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“viscosity” question, this was excluded from the questionnaire. The questionnaire was a visual
analog scale with 0 (no or minimal) at the left and 10 (the most severe) at the right end of a line.
For analysis, the analog scores for frequency, color and volume were grouped into three levels,
while the analog scores for frequency of prosthesis removal were grouped into two levels (Figure
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1). Lower eyelid laxity14, lagophthalmos, MGD15, blinking rate at rest (number of blinking/
minute) 16, 5-minute Schirmer test17, tear meniscus height based on slit lamp examination18, time
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and rate of positivity of Flourscein dye disappearance test (grade 0 and 1 as negative and grade 2
and 3 as positive)19,20, lacrimal sac regurgitation21, and different types of anatomical lacrimal
drainage system obstruction (punctal assessment22, diagnostic probing and irrigation test23) were
recorded for the analysis. Scintigraphy results were classified as normal, presac, preduct, and
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MGD in anophthalmic socket, plugged meibomian gland orifice involving ≥1/3 of the lower
eyelid15 was considered as MGD on the anophthalmic socket side in this study.
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All the data were entered with SPSS (IBM SPSS Statistics for Windows, Version 19.0. Armonk,
NY: IBM Corp.). Paired sample t-test (comparing means between two sides), Wilcoxon signed
rank test (comparing categorical data between two sides), independent sample t-test (comparing
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means in categorical data with 2 options), One way ANOVA with or without Post Hoc test
(comparing means in categorical data with >2 options), and Chi-square test (comparing
categorical data) were used for analysis. P value of less than 0.05 was considered significant. All
the variables were also assessed against duration of prosthetic wearing, presence of eyelid laxity,
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Results
There were 66 consecutively recruited subjects with acquired unilateral anophthalmic socket in
whom 16 subjects were excluded because of socket complications (7), ocular adnexal trauma or
surgery (4), incomplete visits (3), and being on eye drops (2). Included (50) were 28 females and
22 males with a mean age of 31.3 (SD=16.8, range= 7-67) years. Mean time period of prosthetic
wearing was 96.1 (SD=85.8, range= 6- 408) months. Trauma (22), Tumor (13), phthisis bulbi
(13), panophthalmitis (1) and painful blind eye (1) were the reasons for enucleation (38),
evisceration (8), and conjunctival flap (4) procedures. Conjunctival flap had been performed in
subjects with traumatic auto-enucleation who did not consent for further surgery.
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All the subjects scored 1 or more for all the items in the questionnaire with regard to the
discharge characteristics (frequency, color, volume) and prosthesis removal (Table 1).
Conjunctival papillary reaction in all and some giant papillae in 3 subjects was observed on slit
lamp examination. MGD was present in 58% (29/50), different degrees of lagophthalmos
(mean=2.52 mm, SD=1.76, range= 1-8) in 80% (40/50), and lower eyelid laxity in 46% (23/50)
of the subjects. Mean blinking rate was 17.8/minute (SD=3.07, range= 11-25). No conjunctival
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papillary reaction, MGD, eyelid laxity, and lagophthalmos were observed on the normal side.
Lacrimal sac regurgitation test was negative in all the subjects. The anophthalmic socket side, as
compared to the normal side, showed a significantly lower Schirmer value and tear meniscus
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height and higher frequency of positive flourscein dye disappearance test, anatomical lacrimal
drainage system obstruction on irrigation, and physiological lacrimal drainage system
obstruction on scintigraphy (Table 2). Majority of lacrimal drainage system obstructions were
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incomplete (Table 2) and in the upper parts (puncti, canaliculi, common canaliculus) of lacrimal
drainage system (Table 3).
Subjects with frequent prosthesis removal had a significantly (P=0.02) higher frequency of
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discharge than subjects with less frequent prosthesis removal (96.6% vs. 70%). Whereas, color
(P=0.4) and volume of discharge (P=0.5) were not significantly different between these two
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groups. Mean age, Schirmer value, and tear meniscus height as well as results of Flourscein dye
disappearance test, lacrimal scintigraphy and irrigation did not have any significant impact on the
characteristics of discharge and frequency of prosthesis removal (0.06<P<0.9).
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A significantly higher blinking rate was observed in subjects reporting very frequent
(mean=19/min., SD=3.7) compared to those reporting less frequent discharge (mean=15.1/min.,
SD=3.4) and in subjects reporting frequent (mean=18.6/min., SD=2.5) compared to those
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reporting less frequent prosthesis removal (mean=16.8/min., SD=3.4) (P=0.02 and 0.04,
respectively). The blinking rate was higher in subjects reporting severe discharge volume
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Mean Schirmer value and tear meniscus height of anophthalmic socket were not significantly
different between obstructed (irrigation and scintigraphy tests) versus open lacrimal drainage
systems (0.2<P<0.8).
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None of the variables were significantly different between ≤4 years (22/50) versus >4 years
(28/50) of prosthetic wearing and presence (29/50) versus absence (21/50) of MGD (0.1<P<0.9).
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Subjects with (23/50) as compared without (27/50) lower eyelid laxity showed a significantly
longer dye disappearance time (12.8, SD=2.5 versus 10.1, SD=3.3 minutes; P=0.01) and
positivity of Flourscein dye disappearance test (23/23= 100% versus 21/27= 77.7%; P=0.04).
However, other variables did not differ significantly between these groups (0.1<P<0.9).
Sockets with lagophthalmos showed significantly higher frequencies of discharge and prosthesis
removal, but no other significant differences (Table 4).
Discussion
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Discharge was frequent or very frequent in 85%, mucoid or mucopurulent in 90%, and moderate
to severe in 86% of the subjects (Table 1). Certainly, the prosthesis itself could produce
discharge from foreign body related conjunctival inflammation. In fact, Pine et al.25 showed a
significant association between the frequency of discharge and severity of conjunctival
inflammation. While discharge frequency may be associated with the severity of conjunctival
inflammation, the inflammation may not be associated with prosthetic deposits25, nor to the
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prosthetic care regimen8, 26. Therefore, other factors, such as abnormal tear production, lacrimal
drainage insufficiency or eyelid malfunction, may produce the conjunctival inflammation and
subsequent discharge.
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A significantly lower Schirmer value and tear meniscus height (0.13mm) in anophthalmic
sockets implies a tear film impairment. Anophthalmic sockets may produce Schirmer test scores
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of less than 3mm in up to 75% of cases; interestingly, punctual occlusion improves symptoms
and discharge in only 60% of these cases, implying factors in addition to aqueous deficiency lead
to the tear film impairment. 10 Our study and others9 show that MGD may be one of these
factors, and treatment of both MGD and aqueous tear deficiency might benefit anophthalmic
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socket subjects with discharge and discomfort.
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Anatomical lacrimal drainage system obstruction (diagnostic probing and irrigation) was
observed in 54% (27/50) in which the majority (24/27, 88.8%) represented incomplete
obstruction (Table 2). Upper lacrimal drainage system (punctum, canaliculus, common
canaliculus) was the only site of anatomical obstruction in 66.6% (18/27) and in association with
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nasolacrimal duct obstruction in 22.2% (6/27) (Table 3). Furthermore, scintigraphy showed an
even higher number of obstruction (36/50, 74%) in which the majority (23/36, 63.8%) had
complete obstruction. Similar to the irrigation test, the majority (29/36, 80.5%) showed an upper
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lacrimal drainage system obstruction (pre-sac and pre-duct) (Table 3). Our data demonstrate that
a significant proportion of acquired anophthalmos cases are associated with lacrimal
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obstructions. The relationship between the lacrimal obstructions and anophthalmic discharge
remains to be determined.
Change in eyelid position, impairment of tear film, MGD, eyelid laxity, and lagophthalmos may
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cause the punctal stenosis in anophthalmic socket subjects (Table 2). On the other hand, lacrimal
drainage system obstructions may lead to discharge, by producing changes in the normal flora
and tear composition, which may then produce conjunctival inflammation. Unrecognized
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lacrimal drainage obstruction in anophthalmic socket has been reported to presumably cause
chronic discharge and contracted socket in a case report. 13 Interestingly, the anophthalmic
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sockets with drainage obstructions in this study did not demonstrate the expected higher
Schirmer values or tear meniscus heights. This may be due to the incomplete nature of most
obstructions found in this study. It remains unclear if treatment of these obstructions could
improve the discharge.
Mean blinking rate was significantly higher in subjects with higher frequency of discharge and
prosthesis removal. Correlation between blink rate, prosthesis removal and discharge frequency
may all stem from increased irritation from an unknown cause(s), and frequent removal of the
prosthesis could be one of the causes. Prosthesis removal for cleaning does not have a set rule. A
survey of recommendations on the prosthetic care showed a variety of removal recommendations
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by ocularists, from every week to when it is irritating. 4 Vasquez and Linberg27showed that
subjects with frequent prosthesis removal had a significantly higher proportion of gram negative
bacteria in their socket than in normal fellow eye. Removal and reinsertion of prosthesis can
potentially irritate the conjunctiva and traumatize the eyelid which in consequence may lead to a
more discharge. Therefore, less frequent prosthesis removal could be recommended for subjects
with discharge. On the other hand, a high frequency of lagophthalmos (80%) in our series
suggests that socket irregularities such as fornix shortening may play role in pathophysiology of
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discharge.
Not assessing the severity of conjunctival inflammation and fornix depth represent limitation of
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this study. Not simultaneously assessing the prosthetic related causes of discharge like deposits
and smoothness of surface represents another limitation of this study. While assessment of socket
cytology and bacteriology were not the aim of this study, such laboratory measures could be
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assessed against the clinical measures to determine if any correlations exist.
Anophthalmic sockets with discharge may exhibit signs of dryness and lacrimal obstruction, as
well as MGD, laxity and conjunctivitis. There may be a relationship between prosthesis removal
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and signs and symptoms, though a cause-and-effect relationship cannot be yet established.
Treatment of discharge may require treatment of these multiple factors, and further study is
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required to determine if and what treatments may help.
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Acknowledgement/ Disclosure
a) FUNDING/SUPPORT: This study was financially supported by Iran University Eye
Research Center. The sponsor or funding organization had no role in the design or
conduct of this research.
b) FINANCIAL DISCLOSURES: No financial disclosure for any authors.
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c) OTHER ACKNOWLEDGMENT: No
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References
1. Pine K, Sloan B, Stewart J, Jacobs RJ. Concerns of anophthalmic patients wearing artificial
eyes. Clin Experiment Ophthalmol 2011;39(1):47-52.
2. Pine KR, Sloan B, Jacobs RJ. Biosocial profile of New Zealand prosthetic eye wearers. N Z
Med J 2012;125(1363):29–38.
3. Pine KR, Sloan BH, Jacobs RJ. A proposed model of the response of the anophthalmic socket
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to prosthetic eye wear and its application to the management of mucoid discharge. Med
Hypotheses 2013;81(2):300-5.
4. Osborn KL, Hettler D. A survey of recommendations on the care of ocular prostheses.
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Optometry 2010;81(3):142-5.
5. Pine K, Sloan B, Stewart J, Jacobs RJ. A survey of prosthetic eye wearers to investigate
mucoid discharge. Clin Ophthalmol 2012;6:707-13.
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6. Bonaque-González S, Amigó A, Rodríguez-Luna C. Recommendations for post-
adaption care of an ocular prosthesis: A review. Cont Lens Anterior Eye 2015;38(6):397-401.
7. Pine KR, Sloan B, Han KI, Swift S, Jacobs RJ. Deposit buildup on prosthetic eye material (in
vitro) and its effect on surface wettability. Clin Ophthalmol 2013;7:313-9.
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8. Kim JH, Lee MJ, Choung HK, et al. Conjunctival cytologic features in anophthalmic patients
wearing an ocular prosthesis. Ophthal Plast Reconstr Surg 2008;24(4):290-5.
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9. Jang SY, Lee SY, Yoon JS. Meibomian gland dysfunction in longstanding prosthetic eye
wearers. Br J Ophthalmol 2013;97(4):398-402.
10. Vardizer Y, Lang Y, Mourits MP, Briscoe MD. Favorable effects of lacrimal plugs in
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socket contraction presenting 20 years later: a case report. Cutan Ocul Toxicol 2008;27(2):87-9.
14. Beigi B, Kashkouli MB, Shaw A, Murthy R. Fornix fat prolapse as a sign for involutional
entropion. Ophthalmology 2008;115(9):1608-12.
15. Kashkouli MB, Fazel AJ, Kiavash V, Nojomi M, Ghiasian L. Oral azithromycin versus
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17. Kashkouli MB, Pakdel F, Amani A, Asefi M, Aghai GH, Falavarjani KG. A modified
Schirmer test in dry eye and normal subjects: open versus closed eye and 1-minute versus 5-
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21. Kashkouli MB, Parvaresh M, Modarreszadeh M, Hashemi M, Beigi B. Factors affecting the
success of external dacryocystorhinostomy. Orbit 2003;22(4):247-55.
22. Kashkouli MB, Beigi B, Murthy R, Astbury N. Acquired external punctal stenosis: etiology
and associated findings. Am J Ophthalmol 2003;136(6):1079-84.
23. Kashkouli MB, Pakdel F, Hashemi M, et al. Comparing anatomical pattern of topical anti-
glaucoma medications associated lacrimal obstruction with a control group. Orbit 2010;29(2):65-
9.
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24. Jabbour J, Van der Wall H, Katelaris L, Leslie J, Mackey D, Ghabrial R. Quantitative
lacrimal scintigraphy in the assessment of epiphora. Clin Nucl Med 2008;33(8):535-41.
25. Pine KR, Sloan B, Stewart J, Jacobs RJ. The response of the anophthalmic socket to
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prosthetic eye wear. Clin Exp Optom 2013;96(4):388-93.
26. Chang WJ, Tse DT, Rosa RH, Huang A, Johnson TE, Schiffman J. Conjunctival cytology
features of giant papillary conjunctivitis associated with ocular prostheses. Ophthal Plast
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Reconstr Surg 2005;21(1): 39–45.
27. Vasquez RJ, Linberg JV. The anophthalmic socket and the prosthetic eye. A clinical and
bacteriologic study. Ophthal Plast Reconstr Surg 1989;5(4):277–80
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Figure Legend
Figure 1. Questionnaire with visual analog scale (10 is the most severe) for self-reporting of the
discharge characteristics (frequency, color and volume) and frequency of prosthesis removal in
subjects with acquired anophthalmic socket.
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Table 1. Discharge characteristics and frequency of prosthesis removal among 50 subjects with
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Color Purulent 5 (10%)
Mucopurulent 15 (30%)
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Mucoid 30 (60%)
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Frequency Very frequent 13 (26%)
Frequent 30 (60%)
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Less frequent 7 (14%)
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Volume Severe 17 (34%)
Moderate 26 (52%)
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Mild 7 (14%)
Table 2. Comparing the results of 5-minute Flourscein dye disappearance test (FDDT), tear
meniscus height (TMH) in mm, Schirmer test in mm, lacrimal scintigraphy, and lacrimal
irrigation between anophthalmic socket and normal eye of 50 subjects with acquired unilateral
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anophthalmic socket.
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Anophthalmic socket (50) Normal (50) P value
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FDDT Mean 11.4 (3.3) [5-15] 6.9 (3.01) [5-15] 0.001
(SD) [range]
Positive 44 (88%)
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Negative 6 (12%) 33 (66%)
Mean TMH 0.1 (0.05) [0- 0.3] 0.2 (0.07) [0.1-0.4] 0.001
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(SD) [range]
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Mean Schirmer test 5.4 (1.4) [3-8] 11.6 (0.9) [10-14] 0.001
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(SD) [range]
obstruction
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Normal 14 (28%) 39 (78%)
Presac 4 (8%) 0
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Scintigraphy Preduct 25 (50%) 8 (16%)
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Intraduct 7 (14%) 3 (6%)
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Punctum (P) 14 (28%) 1 (2%)
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Canaliculus 3 (6%) 5 (10%)
(C)
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canaliculus
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duct (NLD)
C + NLD 2 (4%) --
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CC + NLD 1 (2%) --
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P + NLD 2 (4%) --
P+C+NLD 1 (2%) --
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(40) (10)
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Frequency frequent
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of frequent 25 (62.5%) 5 (50%) 0.02
discharge
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Less 3 (7.5%) 4 (40%)
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frequent
frequent
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