Retinal OCT and (mfERG) Related to Age, Sex, and the Use of Anti-inflammatory Medications

• Sponsor: Norwegian University of Science and Technology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00476593
• Collaborator: St. Olavs Hospital (Other)
• Enrollment: 218
• Locations: 2
• Arms: 2
• Actual Duration (Months): 63
• Patients Per Site: 109
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

Retinal optical coherence tomography (OCT) is an established technology which enables a detailed cross-sectional visualization of the retinal micro-anatomy, and an objective measurement of its thickness in-vivo. Multifocal electroretinogram (MfERG) measures function of the central retina. Both technologies are relatively new and they provide complimentary to each other information on retinal anatomy and function.

The aims of this study is to establish normal ranges for OCT and mfERG measurements related to age, gender and reproductive factors such as parity and the use of contraception in Norwegians; to assess the presumably healthy central retina with the use of anti-inflammatory medication with relation to age and sex ; to study the frequency and extent of retinal thickening and change in retinal function in patients with anterior uveitis not complicated with macular edema; to assess whether the presence of the HLA-B27 haplotype or uveitis recidive affects macular thickening/function in uveitis.

Condition or Disease	Intervention/Treatment	Phase
Uveitis; Iritis; Iridocyclitis; Anterior Uveitis; Macular Edema	Drug: Diclofenac; Drug: Dexamethasone	N/A

Detailed Description

Normal optical coherence tomography (OCT) and Multifocal electroretinogram (MfERG) measurements may vary with race, age, sex, parity and the use of hormone therapy in health. It has therefore been recommended to gather normative data on the individual OCT/MfERG equipment in each laboratory. This is the reason why we gathered our local normative material on both machines. We also assessed our normative material on the OCT in relation to age, sex, parity and the use of contraception for future matching with patients.

It has been hypothesized that para-inflammation states are involved in retinal aging in health. We assume that the age-related changes we observed in our normative OCT material are related to low-grade chronic inflammation in the retina. We therefore assessed the effect of to commercially available anti-inflammatory eye drops- diclofenac and dexamethasone,which are often used in inflammation-related states in ophthalmology for their effect on macular thickness in health and with aging.

Uveitis is a frank intraocular inflammation which may lead to macular edema. Macular edema is often transient in uveitis and its presence has been previously reported in severe or long-lasting uveitis. In some cases mecular edema may become chronic or refractory to treatment. However, whether uncomplicated anterior uveitis with no clinically evident macular edema leads to macular thickening detectable with the OCT, or whether monolateral uveitis may cause bilateral macular thickening is not known. We therefore assesed both eyes of patients with anterior uveitis for macular thickening with the OCT.

To correlate macular anatomy with its function some subjects included in the OCT study were also examined with the mfERG. However, at present the MfERG result have not been analyzed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 218 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Retinal Optical Coherence Tomography and Multifocal Electroretinogram; Establishing Normal Ranges Related to Age and Reproductive Factors; With the Use of Anti-inflammatory Medications;In Uncomplicated Anterior Uveitis; Anatomy and Function.
• Actual Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diclofenac Preservative- free Diclofenac Na 0.1 % eye drops were applied in one consecutively assigned eye of healthy volunteers four times a day for three days, after which macular thichness was measured in both subjects' eyes with the OCT .	Drug: Diclofenac; Preservative- free Diclofenac Na 0.1% eye drops (Voltaren Ophta SDU;Novartis Pharms). One drop four times daily in one eys for three days. The evaluation of macular thickness/function after 3 days use of anti-inflammatory eye drops in healthy subjects is the only sub-study involving an intervention design.; Other Names: Voltaren (Ophta SDU;Novartis Pharms) eye drops.
Experimental: Dexamethasone Benzalkonium-reserved Dexamethasone Sodium Phosphate 0.1% was applied in one consecutively assigned eye of healthy volunteers six times a day for three days, after which macular thickness was assessed in both subjects's eyes with the OCT.	Drug: Dexamethasone; Dexamethasone sodium phosphate 0.1% eye drops (Spersadex OmniVision, Novartis Pharma), one drop six times daily for three days in one eye. Pharms). One drop four times daily in one eys for three days. The evaluation of macular thickness/function after 3 days use of anti-inflammatory eye drops in healthy subjects is the only sub-study involving an intervention design.; Other Names: Spersadex (OmniVision, Novartis Pharma)eye drops.

Outcome Measures

Primary Outcome Measures

1. Macular Thickness Measured With the OCT; in Relation to Age, Sex, Reproductive Factors and the Use of Anti-inflammatory Eye Drops in Health; in Uncomplicated Anterior Uveitis. [Macular thickness measured with the OCT]

   Macular thickness was assessed with the OCT in healthy subjects and in patients with anterior uveitis. Data was analyzed with respect to age, sex, parity, the use of hormonal therapy, after treatment with to types of anti-inflammatory eye drops, and in uncomplicated uveitis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Adults healthy volunteers and adult patients with anterior uveitis who wish to participate.

Exclusion Criteria:

• Patients with anterior uveitis who have other systemic diseases/conditions not related to their anterior uveitis, like high blood pressure, diabetes or epilepsy.

• Patients with ocular comorbidity or compliactions to their anterior uveitis, such as elevated ocular pressure or glaucoma.

• Previous or current macular edema or other posterior segment complications related to uveitis.

• Subjects with visual acuity worse than 0.8

• Subjects/patients with cataracts or other ocular media opacities

• Subjects/patients who are allergic to local anesthesia or mydriatics.

• Subjects/patients with high myopia/hyperopia

• Subjects/patients who have had intraocular surgery, although previous uncomplicated LASIK correction for low-grade myopia were accepted.

• Subjects/patients who cooperate poorly.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Ophthalmology, St Olavs University Hospital	Trondheim		Norway	7006
2	Department of Neuroscience, Norwegian University of Science and Technology	Trondheim		Norway	7491

Sponsors and Collaborators

• Norwegian University of Science and Technology
• St. Olavs Hospital

Investigators

• Study Director: Tor B Elsås, Professor, Department of Ophthalmology, St. Olavs University Hospital, Trondheim, Norway
• Study Chair: Trond Sand, Professor, Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
• Principal Investigator: Alexandra Wexler, Dr, Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Norwegian University of Science and Technology
• ClinicalTrials.gov Identifier: NCT00476593
• Other Study ID Numbers: 47026200; NSD 200500943; REK 4.2005.13
• First Posted: May 22, 2007
• Last Update Posted: May 1, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Norwegian University of Science and Technology: Uveitis; Iritis; Macular Thickness; HLA-B27 related; Macular edema; Macular thickening; OCT; mfERG; Eye drops; Dexamethosone; Diclofenac; Retinal aging
• Additional relevant MeSH terms: Macular Edema; Uveitis; Uveitis, Anterior; Iridocyclitis; Iritis; Dexamethasone; Diclofenac; Lactitol; Ophthalmic Solutions

Study Results

Participant Flow

Recruitment Details	Healthy subjects were recruited from students and staff at St. Olavs University Hospital and NTU for ophthalmic examination at the Department of Ophthalmology and mfERG testing at NTU, May 05- Sept. 07. From Sept.07 -sept.08 patients with uveitis were recruited from the Dep. of Opthalmology, healthy volunteers- both for OCT examination at the Dep.
Pre-assignment Detail	We chose to focus primary on the OCT results because mfERG equipement was moved and its software was updated. MfERG results will be analyzed later. The main reason for participant exclusion in this study was either bad OCT scan quality or participant withdrawal because examinations turned out to be more time consuming then they thought.

Arm/Group Title	A Diclofenac	B Dexamethasone	Patients With Anterior Uveitis	Healthy Volunteers
Arm/Group Description	Preservative- free Diclofenac Na 0.1 % eye drops were applied in one consecutively assigned eye of healthy volunteers four times a day for three days, after which macular thichness was measured in both subjects' eyes with the OCT .	Benzalkonium-reserved Dexamethasone Sodium Phosphate 0.1% was applied in one consecutively assigned eye of healthy volunteers six times a day for three days, after which macular thickness was assessed in both subjects's eyes with the OCT.	Patients with anterior uveitis were recruited from the Department of Ophthalmology. They were treated for their uveitis and OCT scans of their both eyes were taken on follow up.	Healthy volunteers recruited from students and staff at St Olavs University hospital and NTU went through an opthalmologic examination and OCT scans were taken of their both eyes. This groups was to serve as healthy controls and as matching normative data for patients
Period Title: Overall Study
STARTED	32	19	38	129
COMPLETED	22	17	30	107
NOT COMPLETED	10	2	8	22

Baseline Characteristics

Arm/Group Title	A Diclofenac	B Dexamethasone	Patients With Anterior Uveitis	Healthy Volunteers	Total
Arm/Group Description	Preservative- free Diclofenac Na 0.1 % eye drops were applied in one consecutively assigned eye of healthy volunteers four times a day for three days, after which macular thichness was measured in both subjects' eyes with the OCT .	Benzalkonium-reserved Dexamethasone Sodium Phosphate 0.1% was applied in one consecutively assigned eye of healthy volunteers six times a day for three days, after which macular thickness was assessed in both subjects's eyes with the OCT.	Patients with anterior uveitis were recruited from the Department of Ophthalmology. They were treated for their uveitis and OCT scans of their both eyes were taken on follow up.	Healthy volunteers recruited from students and staff at St Olavs University hospital and NTU went through an opthalmologic examination and OCT scans were taken of their both eyes. This groups was to serve as healthy controls and as matching normative data for patients	Total of all reporting groups
Overall Participants	22	17	30	107	176
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	22 100%	17 100%	29 96.7%	107 100%	175 99.4%
>=65 years	0 0%	0 0%	1 3.3%	0 0%	1 0.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.2 (10.9)	46.2 (11.4)	40.5 (2.3)	42.4 (11.8)	45.1 (11)
Sex: Female, Male (Count of Participants)
Female	15 68.2%	13 76.5%	15 50%	62 57.9%	105 59.7%
Male	7 31.8%	4 23.5%	15 50%	45 42.1%	71 40.3%
Region of Enrollment (participants) [Number]
Norway	22 100%	17 100%	30 100%	107 100%	176 100%

Outcome Measures

1. Primary Outcome

Title	Macular Thickness Measured With the OCT; in Relation to Age, Sex, Reproductive Factors and the Use of Anti-inflammatory Eye Drops in Health; in Uncomplicated Anterior Uveitis.
Description	Macular thickness was assessed with the OCT in healthy subjects and in patients with anterior uveitis. Data was analyzed with respect to age, sex, parity, the use of hormonal therapy, after treatment with to types of anti-inflammatory eye drops, and in uncomplicated uveitis.
Time Frame	Macular thickness measured with the OCT

Outcome Measure Data

Analysis Population Description

Enrolled healthy subjects and patients with anterior uveitis who volunteered through enrollment period

Arm/Group Title	A Diclofenac	B Dexamethasone	Patients With Anterior Uveitis	Healthy Volunteers
Arm/Group Description	Preservative- free Diclofenac Na 0.1 % eye drops were applied in one consecutively assigned eye of healthy volunteers four times a day for three days, after which macular thichness was measured in both subjects' eyes with the OCT .	Benzalkonium-reserved Dexamethasone Sodium Phosphate 0.1% was applied in one consecutively assigned eye of healthy volunteers six times a day for three days, after which macular thickness was assessed in both subjects's eyes with the OCT.	Patients with anterior uveitis were recruited from the Department of Ophthalmology. They were treated for their uveitis and OCT scans of their both eyes were taken on follow up.	Healthy volunteers recruited from students and staff at St Olavs University hospital and NTU went through an opthalmologic examination and OCT scans were taken of their both eyes. This groups was to serve as healthy controls and as matching normative data for patients
Measure Participants	22	17	30	107
Mean (Standard Deviation) [Macular Thickness in micron]	268 (13)	272 (16)	276 (21)	267 (13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A Diclofenac, B Dexamethasone
	Comments	Subjects who received diclofenac or dexamethasone eye drops in one eye. Macular thickness in both were compared between same subjects' eyes after 3 day's treatment. Diclofenac and dexamethasone treated eyes were not compared with each other, but with the contralateral eye of same subject by a paired Student's t-test in each medication group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments	Hypothesis: the use of diclofenac/dexamethasone does not influence macular thickness in treated eyes compared with untreated eyes of same subject.
	Method	t-test, 2 sided
	Comments	The possible effect of both anti-inflammatory medications was tested in relation to participants' age and gender

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Patients With Anterior Uveitis, Healthy Volunteers
	Comments	Patient's healthy eyes were compared with sex and age matched healthy controls with Two Sample Student't t-test. Null hypothesis was that quiet, currently unaffected eyes of patients had same macular thickness as age and sex matched controls.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Arm/Group Title	A Diclofenac		B Dexamethasone		Patients With Anterior Uveitis		Healthy Volunteers
Arm/Group Description	Preservative- free Diclofenac Na 0.1 % eye drops were applied in one consecutively assigned eye of healthy volunteers four times a day for three days, after which macular thichness was measured in both subjects' eyes with the OCT .		Benzalkonium-reserved Dexamethasone Sodium Phosphate 0.1% was applied in one consecutively assigned eye of healthy volunteers six times a day for three days, after which macular thickness was assessed in both subjects's eyes with the OCT.		Patients with anterior uveitis were recruited from the Department of Ophthalmology. They were treated for their uveitis and OCT scans of their both eyes were taken on follow up.		Healthy volunteers recruited from students and staff at St Olavs University hospital and NTU went through an opthalmologic examination and OCT scans were taken of their both eyes. This groups was to serve as healthy controls and as matching normative data for patients
All Cause Mortality
	A Diclofenac		B Dexamethasone		Patients With Anterior Uveitis		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	A Diclofenac		B Dexamethasone		Patients With Anterior Uveitis		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	A Diclofenac		B Dexamethasone		Patients With Anterior Uveitis		Healthy Volunteers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.