Clinical trial NCT02718547: The Relationship Between Intraocular Pressure and Macular Edema in Patients With Diabetic Macular Edema
Official title: The Effect of Reducing the Intraocular Pressure by Using Alphagan Drops and Macular Edema in Patients With Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Complications of Diabetes Mellitus
Keywords: Diabetes mellitus
Diabetic macular edema
Intra ocular pressure
Ocular perfusion pressure
Retinal perfusion
Lead sponsor: Meir Medical Center
Sponsor class: OTHER
Collaborators: name: Meir Hospital, Kfar Saba, Israel
First posted: 2016-03-24
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The Investigators propose to examine the effect of lowering the intraocular pressure on macular edema in Participants diagnosed with diabetic macular edema. Our theory is based on the assumption that lower intraocular pressure means higher Ocular Perfusion pressure, which may cause an improvement in retinal perfusion and thus an improvement in retinal oxygenation and reduced edema

Detailed description: Ocular perfusion pressure (ocular perfusion pressure - OPP), considered the driving force of ocular blood flow. Perfusion pressure is defined as the difference between the artery and vein blood pressure. Because ocular venous pressure is the same or slightly higher than the IOP (intra ocular pressure - IOP), it is common to estimate the OPP as the difference between the arterial blood pressure of IOP. The OPP is critical for diffusion of oxygen, nutrients and metabolic waste from retinal imaging, and decrease it may reduce blood flow to the eye and lead to ischemia or hypoxia. the OPP is controlled by a complex system of Autoregulation. Much has been written about the relationship between the OPP and glaucoma, and agreed that OPP is a low risk factor for this disease.

Diabetic macular edema (DME) is the most common cause of vision loss in developed countries the working-age.

Many studies were carried out in recent years in an attempt to better understand the pathophysiology of Diabetic macular edema, and there is consensus in the scientific literature that hypertension have a significant effect on Diabetic macular edema. this relationship is much more complex than it seems at first glance. Paques and his team have shown an inverse association between blood pressure to drop night and Diabetic macular edema. LARSEN and his team have shown a similar trend.

Hayreh published an article from 2007, where he described the mechanism of improvement of the Diabetic macular edema with discontinuation of hypertensive treatment and thereby raising blood pressure. In this article, Hayreh describes hypoxia as a significant factor in Diabetic macular edema, and demonstrated that treatment of hypoxia by increasing the OPP brought good results in terms of macular thickness If so, it seems that there is not only a link between levels of oxygenation of the retina to Diabetic macular edema, but that improved oxygenation of the retina could lower the levels of macular edema in these patients. If a way were found to improve retinal perfusion, this may lead to an improved oxygenation and reduced edema. The Investigators propose to examine the relationship between macular edema IOP in Participants with Diabetic macular edema, thinking that high IOP means lower OPP, which means increased risk for developing macular edema in this Participants group.

Eligibility criteria: Inclusion Criteria:

* Participants with a diagnosis of diabetic macular edema over the age of 18 which are eligible to sign an agreement to participate in the study
* Presence of DME (based on clinical examination of retinal specialist + OCT) in both eyes with an edema thickness ranged from 350 to 800 microns
* Media lucid enough to allow sufficient quality photographs by OCT

Exclusion Criteria:

* Patients which do not have a valid diagnosis of DME (Diabetic Macular Edema)
* Patients with problems that can cause macular edema in any other:

  * Age-Related Macular Degeneration
  * Central retinal vein occlusion (CRVO)/Branch retinal vein occlusion (BRVO) /central retinal artery occlusion (CRAO) / branch retinal artery occlusion (BRAO)
  * Epiretinal membrane (ERM) or Vitreo-macular traction (VMT)
  * Patients who are Pseudophakic in one eye or pseudophakic in both eyes for less than a year
  * Patients treated in order to reduce the DME by intra-vitreal injection or by laser in the past six months
  * Patients which are currently treat with Intra ocular Pressure lowering drops in at least one eye, or have been treated in the past with laser of any kind or with surgery
  * Patients who underwent Pars plana vitrectomy one or both eyes
  * Patients who cannot undergo an OCT examination
  * Patients who want prefer to be treated by the current practices based on clinical judgment
  * Patients with a condition that requires an intervention or laser surgery during the 3 months of study, such as active Proliferative diabetic retinopathy, vitreous hemorrhage or other similar conditions

Primary outcomes:
measure: Change of at least 50 micron in Macular edema
timeFrame: Baseline measurement will be conducted at the recruitment of the participant, the second measurement will be preformed after one moth from recruitment and the third and last measurement will be preformed after 3 months from recruitment
Secondary outcomes:
Other outcomes:
Locations:
city: Kfar Saba
country: Israel
facility: Meir Medical center
Study officials:
References:
citation: Glucksberg MR, Dunn R. Direct measurement of retinal microvascular pressures in the live, anesthetized cat. Microvasc Res. 1993 Mar;45(2):158-65. doi: 10.1006/mvre.1993.1015.
citation: Schmidl D, Garhofer G, Schmetterer L. The complex interaction between ocular perfusion pressure and ocular blood flow - relevance for glaucoma. Exp Eye Res. 2011 Aug;93(2):141-55. doi: 10.1016/j.exer.2010.09.002. Epub 2010 Sep 22.
citation: Thomas BJ, Shienbaum G, Boyer DS, Flynn HW Jr. Evolving strategies in the management of diabetic macular edema: clinical trials and current management. Can J Ophthalmol. 2013 Feb;48(1):22-30. doi: 10.1016/j.jcjo.2012.11.012.
citation: Lasker RD. The diabetes control and complications trial. Implications for policy and practice. N Engl J Med. 1993 Sep 30;329(14):1035-6. doi: 10.1056/NEJM199309303291410. No abstract available.
citation: Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema. Ophthalmology. 1995 Jan;102(1):7-16. doi: 10.1016/s0161-6420(95)31052-4.
citation: Bhagat N, Grigorian RA, Tutela A, Zarbin MA. Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol. 2009 Jan-Feb;54(1):1-32. doi: 10.1016/j.survophthal.2008.10.001.
citation: Matthews DR, Stratton IM, Aldington SJ, Holman RR, Kohner EM; UK Prospective Diabetes Study Group. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Arch Ophthalmol. 2004 Nov;122(11):1631-40. doi: 10.1001/archopht.122.11.1631.
citation: Paques M, Massin P, Sahel JA, Gaudric A, Bergmann JF, Azancot S, Levy BI, Vicaut E. Circadian fluctuations of macular edema in patients with morning vision blurring: correlation with arterial pressure and effect of light deprivation. Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4707-11. doi: 10.1167/iovs.05-0638.
citation: Larsen M, Wang M, Sander B. Overnight thickness variation in diabetic macular edema. Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2313-6. doi: 10.1167/iovs.04-0893.
citation: Hayreh SS. Role of retinal hypoxia in diabetic macular edema: a new concept. Graefes Arch Clin Exp Ophthalmol. 2008 Mar;246(3):353-61. doi: 10.1007/s00417-007-0678-2. Epub 2007 Sep 18.
citation: Vinten M, La Cour M, Lund-Andersen H, Larsen M. Acute effect of pure oxygen breathing on diabetic macular edema. Eur J Ophthalmol. 2012 Aug 8:0. doi: 10.5301/ejo.5000195. Online ahead of print.
citation: Nguyen QD, Shah SM, Van Anden E, Sung JU, Vitale S, Campochiaro PA. Supplemental oxygen improves diabetic macular edema: a pilot study. Invest Ophthalmol Vis Sci. 2004 Feb;45(2):617-24. doi: 10.1167/iovs.03-0557.
citation: Vinten M, la Cour M, Lund-Andersen H, Larsen M. Effect of acute postural variation on diabetic macular oedema. Acta Ophthalmol. 2010 Mar;88(2):174-80. doi: 10.1111/j.1755-3768.2008.01421.x. Epub 2009 Dec 13.
citation: Frederiksen CA, Jeppesen P, Knudsen ST, Poulsen PL, Mogensen CE, Bek T. The blood pressure-induced diameter response of retinal arterioles decreases with increasing diabetic maculopathy. Graefes Arch Clin Exp Ophthalmol. 2006 Oct;244(10):1255-61. doi: 10.1007/s00417-006-0262-1. Epub 2006 Mar 15.