Clinical trial NCT03396809: Punctal Plugs and Iodine Related Discomfort
Official title: The Use of Punctal Plugs in Reducing Iodine Related Ocular Surface Discomfort
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Dry Eye Syndromes
Keywords: punctal plugs
dry eye
ocular surface disease index
Lead sponsor: University of New Mexico
Sponsor class: OTHER
First posted: 2018-01-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Investigators will be performing a case crossover study. First patients who consent will be asked to complete an Ocular Surface Disease Index (OSDI). Those whose score indicates a diagnosis of dry eye will eligible for the study. Three to five days after their intravitreal injection, patients will be contacted over the telephone and asked to complete the OSDI. At their next visit, one month later, a punctal plug will be inserted before their second injection. Three to five days after their second injection, they will be asked to complete the OSDI over the telephone. At their third visit they will receive an intravitreal injection and three to five days after they will be asked to complete a final OSDI. If patients are receiving bilateral intravitreal injections, and the OSDI survey indicates dry eyes bilaterally, then only one of the eyes will be randomly chosen for plug insertion. The other eye will then be used as a control.
Primary purpose: SUPPORTIVE_CARE

Brief summary: Purpose: Intravitreal injection of medications has revolutionized the treatment microvascular diseases. These diseases often require regular, life-long injections. Ensuring patient comfort is important for compliance with long-term treatments. Patients receiving regular intravitreal injections often complain of progressive dry eye related discomfort. These symptoms are likely secondary to the use of povidone iodine as an antiseptic. Investigators hypothesize that punctal plugs could reverse the progressive ocular surface discomfort induced by povidone iodine during the post-procedural state.

Detailed description: Retina specialists treat many diseases of the posterior segment of the eye by the delivery of medications via intravitreal injections. Many of these medications are monoclonal antibodies that need to be injected monthly. Endophthalmitis is a sight threatening complication of intravitreal injections. Limiting this complication is of primary importance in any injection protocol. The gold standard antiseptic used in intravitreal injection is Povidone-iodine (PI). PI is used to clean the surrounding ocular adnexa and is used in a 5% dilution on the ocular surface.

PI has been shown to be corrosive to the cornea, delay healing, and cause patients significant discomfort post injection especially for those with dry eye. Non-steroidal anti-inflammatories, topical anesthetics, and anticholinergics have been shown to decrease post injection discomfort1, but these measures are expensive, do not protect against corneal irritation and do not improve the healing capacity of the eye. There is a need for a cost effective measure that can reduce corneal irritation and improve healing due to the effects of PI. Punctal plugs are FDA approved for the treatment of dry eye. They increase lubrication of the eye by blocking the drainage of tears into the lacrimal sac. Our study would like to investigate the efficacy of punctal plug insertion in the prevention of dry eye symptoms caused by PI following intravitreal injection.

It has been shown that PI is toxic to the cornea at increasing concentrations. Once in contact with corneal epithelium it releases free iodine radicals causing cytotoxicity and apoptosis of cells. This makes it an effective antiseptic for Ophthalmologic procedures, but also causes significant destruction of the healthy corneal tissue2. It has also been shown in rabbits that calf serum is protective against PI induced corneal damage by providing an additional organic substrate for the PI to bind3. It is possible that natural tears can have a similar effect.

Punctal plugs are an extremely cost effective and widely used device to increase the volume of tears on the ocular surface. They block the lacrimal puncta and canalicular system that drains into the nasolacrimal duct, thereby inhibiting drainage of the natural tears into the nasal atria. In patients with dry eye who receive intravitreal injection punctal plugs may be useful in reducing corneal irritation by increasing the volume of natural tears on the ocular surface, which provides an additional organic substrate for the PI solution to bind. This has the potential to decrease the corrosive effects of the PI on the cornea, reduce healing time, and reduce pain in patients with dry eye.

Investigators will be performing a case crossover study. First patients who consent will be asked to complete an Ocular Surface Disease Index (OSDI). Those whose score indicates a diagnosis of dry eye will eligible for the study. Three to five days after their intravitreal injection, patients will be contacted over the telephone and asked to complete the OSDI. At their next visit, one month later, a punctal plug will be inserted before their second injection. Three to five days after their second injection, they will be asked to complete the OSDI over the telephone. At their third visit they will receive an intravitreal injection and three to five days after they will be asked to complete a final OSDI. If patients are receiving bilateral intravitreal injections, and the OSDI survey indicates dry eyes bilaterally, then only one of the eyes will be randomly chosen for plug insertion. The other eye will then be used as a control. There will be no blinding.

Eligibility criteria: Inclusion Criteria:

* Patients seen at Eye Associates of New Mexico Retina Center or the University of New Mexico Eye Clinic
* Three consecutive monthly intravitreal injections
* Patients whose OSDI score indicate dry eye (score greater than 12)
* Greater than 18 years old
* Males and Females

Exclusion Criteria:

* previous punctal plugs
* punctal cautery
* active infection
* history of ocular infection

  1. herpes simplex virus
  2. herpes zoster virus
* previous eyelid trauma

  1. surgery
  2. graft versus host disease
  3. and thyroid eye disease
* Women whom are pregnant or may become pregnant

Primary outcomes:
measure: Reduction in OSDI scores
timeFrame: 1 year
Secondary outcomes:
measure: OSDI scores in patients receiving bilateral injections
timeFrame: 1 year
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: Eye Associates of New Mexico Retina Center
state: New Mexico
Study officials:
affiliation: jjnelson@eyenm.com
name: Jennifer Nelson, COA, ROUB
role: STUDY_DIRECTOR
References:
citation: Georgakopoulos CD, Tsapardoni F, Makri OE. EFFECT OF BROMFENAC ON PAIN RELATED TO INTRAVITREAL INJECTIONS: A Randomized Crossover Study. Retina. 2017 Feb;37(2):388-395. doi: 10.1097/IAE.0000000000001137.
citation: Jiang J, Wu M, Shen T. The toxic effect of different concentrations of povidone iodine on the rabbit's cornea. Cutan Ocul Toxicol. 2009;28(3):119-24. doi: 10.1080/15569520903080511.
citation: Naor J, Savion N, Blumenthal M, Assia EI. Corneal endothelial cytotoxicity of diluted povidone--iodine. J Cataract Refract Surg. 2001 Jun;27(6):941-7. doi: 10.1016/s0886-3350(00)00750-1.
citation: Haddock LJ, Ramsey DJ, Young LH. Complications of subspecialty ophthalmic care: endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor medications. Semin Ophthalmol. 2014 Sep-Nov;29(5-6):257-62. doi: 10.3109/08820538.2014.959616.
citation: Jehangir N, Bever G, Mahmood SM, Moshirfar M. Comprehensive Review of the Literature on Existing Punctal Plugs for the Management of Dry Eye Disease. J Ophthalmol. 2016;2016:9312340. doi: 10.1155/2016/9312340. Epub 2016 Mar 7.