Punctal Plug Retention Rates for the Treatment of Moderate to Severe Dry Eye: A Randomized, Double-Masked, Controlled Clinical Trial




Purpose


To compare retention rates of Super Flex (Eagle Vision, Memphis, Tennessee, USA; Softplug-Oasis Medical Inc, Glendora, California, USA) vs Parasol (Odyssey Medical, Memphis, Tennessee, USA; Beaver Visitec International, Waltham, Massachusetts, USA) punctal plugs.


Design


Randomized, double-masked, interventional controlled clinical trial.


Methods


Institutional study at Hotel Dieu Hospital (Queen’s University) of 50 eyes, from patients with moderate to severe dry eye. Each eye from eligible patients was separately randomized to receive Super Flex or Parasol punctal plugs. The main outcome measure was plug retention at 6 months. Secondary outcome measures included objective tests of Schirmer I (mm), tear meniscus height (mm), tear break-up time (s), inferior fluorescein corneal staining (National Eye Institute [NEI] scale), and average lissamine green conjunctival staining (NEI scale).


Results


Punctal plug retention was significantly different at 6 months ( P = .011). Sixty-eight percent of Parasol plugs were retained compared to 32% of Super Flex plugs. Parasol plugs required less frequent artificial tear use at 6 months ( P = .024). There was a statistically significant improvement in all secondary outcome measures (Schirmer, tear meniscus height, tear break-up time, fluorescein corneal staining) at 6 months within plug groups except conjunctival staining. There were no additional significant differences between groups and no plug complications reported.


Conclusions


Punctal plugs improve symptoms of moderate to severe dry eye; however, retention rates differ significantly. These data will allow us to guide patient decision making for the safe and effective treatment of punctal plugs for moderate to severe dry eye.


The symptoms of ocular surface dryness are some of the most common patient concerns in ophthalmology practices. Not only are symptoms painful and irritating, but dry eye can also affect visual acuity and quality-of-life measures. Punctal plug insertion is a safe and easy office procedure for the treatment of moderate to severe dry eye. Punctal plugs help to maintain aqueous and artificial tears on the ocular surface to reduce both the subjective and objective symptoms of dry eye. Patients often require the insertion of 2–4 plugs and may pay out of pocket for this procedure. Despite their success in reducing the symptoms of dry eye, spontaneous plug loss is a frequent complication. Reportedly this occurs between 20% and 70% of the time and many different designs and materials have been tried to increase retention rate.


In an effort to minimize plug loss a new plug design, Parasol punctal occluder (Parasol; Odyssey Medical, Memphis, Tennessee, USA; Beaver Visitec International, Waltham, Massachusetts, USA), was designed. This design contains a hollow nose, which collapses on insertion and expands within the puncta, thereby limiting the rate of spontaneous loss, promoting a 92% retention rate. No independent studies to date have confirmed this claim.


Thus, the purpose of the study is to compare the retention rate of the commonly used Super Flex (Eagle Vision, Memphis, Tennessee, USA; Softplug-Oasis Medical Inc, Glendora, California, USA) vs the Parasol punctal plug.


Methods


Study Design and Overview


This randomized, double-masked prospective interventional control trial, comparing Parasol punctal plugs and Super Flex punctal plugs, was conducted at Hotel Dieu Hospital, Queen’s University in Kingston, Ontario, Canada and adhered to the tenets of the Declaration of Helsinki. The Queen’s University and Affiliated Teaching Hospitals Health Sciences Research Ethics Board approved the study prior to enrolling study participants. The study is listed on ClinicalTrials.gov , under the identifier NCT01947517 .


Study Population and Inclusion/Exclusion Criteria


Patients were recruited from 1 cornea specialist (S.B.) and 2 general ophthalmology practices (K.S., M.B.). Inclusion criteria included moderate to severe subjective dry eye symptoms as per the Canadian Dry Eye Assessment (CDEA), a validated dry eye symptoms questionnaire based on the Ocular Surface Disease Index (OSDI). The CDEA is a questionnaire that assesses the patient’s dry eye symptoms, environmental influences, and quality-of-life measures. Each response is awarded a score and the final score is determined from the summation of all of the sections. The final score is classified along a scale of mild, moderate, or severe dry eye. Treatment recommendations are then made based on the severity. Exclusion criteria included dry eye secondary to systemic inflammatory conditions, punctal cautery, punctal stenosis, silicone allergy, and inability to attend multiple follow-up visits for 6 months.


Treatment Assignment


Randomization was achieved using a mathematical computer-generated allocation schema based on permuted blocks with blocks of random sizes. Randomization assignment was not released until eligibility was confirmed and signed consent obtained. Each eye was assigned randomly with equal probability to receive either Super Flex or Parasol brand punctal plugs. A comparative photograph of the Parasol and Super Flex punctal plug designs is shown in Figure 1 .




Figure 1


Comparative photograph of equivalent sizes demonstrates the design of the plugs for the treatment of moderate to severe dry eye. The Parasol is the left plug (size medium), and the Superflex is the right plug (size 0.7).


Study Procedures


Participants and all study staff, except an unmasked investigator (A.B.) who inserted punctal plugs, were masked to treatment arms. A punctal gauge was used to correctly measure punctal size, and an appropriately sized punctal plug was selected based on manufacturer’s instrument. One unmasked investigator (A.B.) inserted all plugs to limit any differences in plug insertion technique and all plugs were inserted in the lower puncta. Plug retention and all other secondary outcomes were evaluated by 1 examiner masked to the treatment arms (Z.M.). Disclosures were tracked and none were recorded.


Outcome Measures


Punctal plug retention was assessed at monthly intervals for a total of 6 months. Retention was characterized by last examined date with the punctal plug in place. For example, if a patient returned for his or her 4-month visit, and the plug was gone, the plug was recorded as 3 months of retention. Secondary outcome measures including objective tests of Schirmer I (mm), tear meniscus height as measured at the slit lamp (mm), tear break-up time (TBUT, in seconds), inferior fluorescein corneal staining (National Eye Institute [NEI] scale), and average lissamine green conjunctival staining (NEI scale) were evaluated for each eye. The NEI scale of corneal staining was completed for the inferior cornea, as this is the site most often involved in dry eye disease. The frequency of artificial tear use per day was also assessed subjectively by asking all participants at study visits how often they used artificial tears per day in the previous month.


Sample Determination and Power


Previously published data have suggested retention rates of 30.1%–70.4%. Using these proportions, an alpha of 0.05, and a 2-tailed test, the study would have power of 80.7% to yield a statistically significant result with a sample size of 25 per group.


Statistical Analysis


Statistical analysis for the primary outcome (plug retention at 6 months) was compared using the c 2 test. Secondary outcome measures included improvement in the CDEA, frequency of artificial tear use, Schirmer I, tear meniscus height, tear break-up time, inferior fluorescein corneal staining, and lissamine green conjunctival staining at months 1, 3, and 6. A comparison of age and punctal plug retention was also performed. A repeated measures analysis of variance (ANOVA) was performed for analyses of secondary measures.




Results


In total, 52 eyes of 26 patients were randomized to Parasol (n = 26) or Super Flex (n = 26). The Consolidated Standards of Reporting Trials (CONSORT) flow diagram illustrating participant allocation is available as a Supplemental Figure (Supplemental Material available at AJO.com ). One patient withdrew from the study directly after randomization and was not included for final analysis. Baseline demographics and clinical characteristics were similar between the 2 groups ( Table 1 ). There were no plug-related complications reported, including no plug migration into the canalicular system.



Table 1

Baseline Characteristics of Patients by Treatment Assignment in the Comparison of Punctal Plug Retention Rate for the Treatment of Moderate to Severe Dry Eye


























































































































Characteristics Parasol (n = 25) Super Flex (n = 25) P
Mean (SD) age, y 61.7 (17.67) 58.4 (16.18) .497
Sex
Male, n (%) 3 (12) 2 (4)
Female, n (%) 10 (40) 11 (44)
Punctal plug size, n (%)
0.4 2 (8)
0.5 9 (36)
0.6 7 (28)
0.7 4 (16)
0.8 2 (8)
0.9 1 (4)
X-small (0.2–0.35) 4 (16)
Small (0.35–0.6) 12 (48)
Medium (0.6–0.8) 7 (28)
Large (0.9) 2 (8)
CDEA severity, a n (%)
Moderate 6 (12) 2 (4)
Severe 19 (38) 23 (46)
Mean (SD) 2.76 (0.44) 2.75 (0.46) .990
Artificial tear use per day, mean (SD) 4.56 (1.39) 4.72 (1.97) .741
Schirmer I, mm (SD) 7.00 (3.45) 8.68 (4.83) .163
Tear meniscus height, mm (SD) 0.472 (0.50) 0.468 (0.63) .980
Inferior corneal staining, NEI scale (SD) 3.28 (0.94) 3.60 (1.16) .287
Conjunctival staining, NEI scale (SD) 2.08 (0.57) 2.08 (0.95) >0.999
Tear break-up time, s (SD) 4.04 (1.59) 4.00 (2.16) .941

CDEA = Canadian Dry Eye Assessment; NEI = National Eye Institute.

a CDEA severity: normal = 1, mild = 2, moderate = 3, severe = 4.



Plug Retention


At 6 months, more Parasol plugs were retained (68%; 17/25) compared with Super Flex plugs (32%; 8/25; P = .011; Figure 2 ). Mean retention time was 4.68 and 3.36 months for the Parasol and Super Flex plugs, respectively ( P = .035). There was a trend to early loss in the Super Flex brand, with 48% (n = 12) of spontaneous losses occurring by 2 months compared to 16% (n = 4) of the Parasol plugs. The difference in early loss was significantly different between groups ( P = .032).




Figure 2


Kaplan-Meier curve shows the plug retention comparing the Parasol and the Super Flex punctal plugs. The y-axis demonstrates the proportion retained (0–1.0) while the x-axis demonstrates the plug retention at monthly intervals (0–6 months). The Parasol brand had a higher proportion of plugs retained at 6 months, and the Super Flex brand had a high failure rate at 2 months.


Secondary measures were evaluated at baseline and at months 1, 3, and 6, and are displayed in Table 2 . Secondary measures were analyzed up to last documented date of retention. The CDEA score showed a statistically significant improvement over time for both brands ( P < .001), with no significant effect in comparison between plug brands ( P = .141). The frequency of artificial tear use (number of drops per day) also decreased over time for both brands ( P < .001). This decrease was greater for the Parasol brand ( P = .024). The Schirmer I test measurement (mm) improved significantly over time ( P < .001), with no significant difference between the brands ( P = .797). Tear meniscus height (mm) also improved significantly over time ( P < .001), with no significant difference between the brands ( P = .099). Inferior corneal staining with fluorescein improved significantly over time ( P < .001), with no difference between plug brands ( P = .768). There was no statistically significant difference in conjunctival staining with lissamine green over time ( P = .185) or in comparison between the plug brands ( P = .249). Lastly, tear break-up time (s) improved significantly over time for both brands ( P = .018), with no significant effect in comparison of the plug brands ( P = .475). We found no association between age and retention rate of punctal plugs ( P = .920) or between age and plug brand retention ( P = .497).


Jan 7, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Punctal Plug Retention Rates for the Treatment of Moderate to Severe Dry Eye: A Randomized, Double-Masked, Controlled Clinical Trial

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