Clinical trial NCT03292796: RCT to Investigate if Prostaglandin Analogue Drops Increase the Risk of Cystoid Macular Oedema After Cataract Surgery.
Official title: A Randomised Control Study to Investigate if the Continuation of Prostaglandin Analogue Treatments in the Post-operative Phase of Glaucoma Patients Undergoing Cataract Surgery Increases the Incidence of Cystoid Macular Oedema.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Open Angle Glaucoma and Cataract
Keywords: Open Angle Glaucoma
Cataract
Phacoemulsification,
Cystoid Macular Oedema,
Prostaglandin Analogues
Lead sponsor: Norfolk and Norwich University Hospitals NHS Foundation Trust
Sponsor class: OTHER
First posted: 2017-09-26
Enrollment: 56
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised Control Trial
Primary purpose: TREATMENT

Brief summary: Post-operative cystoid macular oedema (CMO) is a common complication causing visual loss following routine cataract surgery. This complication is more prevalent in eyes with excessive inflammation as they heal from surgery.

Prostaglandin analogues (PGA) are the commonest first line drugs used in the long-term treatment of primary open angle glaucoma (POAG)- where they reduce the pathologically high pressure in the eye. Prostaglandins are inflammatory mediators.

In the post-operative care of glaucoma patients undergoing cataract surgery, there is a clinical dilemma whether to stop or continue the use of prostaglandin eye drops. Clinical practice is completely dichotomized between continuing and stopping PGA treatment in the postoperative period. There is conflicting scientific literature on the effect of PGA on the incidence of CMO; and only a single randomized control trial (Miyake K, Arch Ophthalmol 1999, 117:34-40), where the post operative regime is not applicable to present practice, compared the incidence of CMO following routine cataract surgery in POAG on PGA.

Detailed description: This study aims to answer the common clinical question of whether or not to stop PGA after routine cataract surgery. Cataract surgery is the commonest operation performed on the NHS and the prevalence of glaucoma is 5% in the population over 80 years old. Thus the clinical dilemma is a common one.

A current literature search reveals that a divided opinion over whether PGAs do increase the incidence of CMO. No study has yet established a causal relationship between the use of PGAs and the development of CMO. Anecdotal reports and small case series have associated peri-operative PGA use with the occurrence of CMO (Henderson BA et al, 2007 J Cataract Refract Surg 33:1550-1558; Moroi SE et al, 1999, Ophthalmology 106:1024-1029). Whilst, in direct contrast, other authors argue CMO as a rare phenomenon and the causative relationship is debated (Schumer RA et al 2000, Curr Opin Ophthalmol 11:94-100; Miyake K et al 2003 J Cataract Refract Surg 29:1800-1810)

The most similar previous study to the one proposed, was by Miyake K et al. (Arch Ophthalmol 1999, 117:34-40). The key difference, though, is in the postoperative drop regime of fluorometholone and diclofenac in that paper and current UK clinical practice of using dexamethasone. In terms of study design, this paper used an invasive method of investigating CMO by fundus fluorescein angiography compared to OCT proposed here.

A recent case report by Agange N \& Mosaed S (Journal of Ophthalmology, 2010) concludes with 'conclusions about causal relationships cannot be made without well-designed, prospective clinical trials addressing this issue'.

This study will therefore use drops that are routinely used in current UK clinical practice and add to the body of evidence that helps answer the question should PGAs be continued after cataract surgery so as to prevent the progression of glaucoma in patients.

* Aim

  * This study investigates if the occurrence of CMO after cataract surgery is affected by the use of PGA drops by patients with glaucoma
  * The null hypothesis states there is no increase in the incidence of CMO on OCT scanning in the 4 weeks following cataract surgery whether PGA eye drops continue or are stopped.
* Design

  * Randomised control study with parallel group design
  * Single masking of outcome assessors

Eligibility criteria: Inclusion Criteria:

* Primary open-angle glaucoma and ocular hypertensive subjects undergoing cataract surgery (routine phacoemulsification and intraocular lens implantation) AND on current topical glaucoma treatment with a prostaglandin analogue eye drop for at least 2 months prior to cataract surgery.
* Subjects capable of giving informed consent

Exclusion Criteria:

* Subjects with additional risk factors for macula oedema (eg. diabetic retinopathy, previous macula oedema, uveitis)
* Subjects with advanced glaucoma

  * Advanced visual field loss (Humphrey Mean Deviation \>-12dB)
  * Advanced glaucomatous disc changes (vertical cup-to-disc ratio \>0.9)
* Subjects with non-controlled intraocular pressure (IOP) (pre-operative IOP \>22 mmHg)
* Any contra-indication to the use of topical prostaglandin drops
* Any contra-indication to the use of routine post-operative dexamethasone 0.1% eye drops
* Pregnancy
* Patients unable to give informed consent
* Intra-operative complication during cataract phacoemulsification and intraocular lens implantation

Primary outcomes:
measure: Occurrence of cystoid macula oedema (CMO) at 4 weeks post operatively
timeFrame: 4 weeks post operatively
Secondary outcomes:
measure: Intraocular pressure (IOP) at 4 weeks post-operatively.
timeFrame: 4 weeks post operatively
Other outcomes:
Locations:
city: Norwich
country: United Kingdom
facility: Norfolk & Norwich University Hospitals NHS Foundation Trust
state: Norfolk
Study officials:
affiliation: Consultant Ophthalmologist
name: Nuwan Niyadurupola, Consultant
role: PRINCIPAL_INVESTIGATOR
References:
citation: Agange N, Mosaed S. Prostaglandin-induced cystoid macular edema following routine cataract extraction. J Ophthalmol. 2010;2010:690707. doi: 10.1155/2010/690707. Epub 2010 Nov 7.
citation: Henderson BA, Kim JY, Ament CS, Ferrufino-Ponce ZK, Grabowska A, Cremers SL. Clinical pseudophakic cystoid macular edema. Risk factors for development and duration after treatment. J Cataract Refract Surg. 2007 Sep;33(9):1550-8. doi: 10.1016/j.jcrs.2007.05.013.
citation: Miyake K, Ota I, Maekubo K, Ichihashi S, Miyake S. Latanoprost accelerates disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema in early postoperative pseudophakias. Arch Ophthalmol. 1999 Jan;117(1):34-40. doi: 10.1001/archopht.117.1.34.
citation: Miyake K, Ibaraki N, Goto Y, Oogiya S, Ishigaki J, Ota I, Miyake S. ESCRS Binkhorst lecture 2002: Pseudophakic preservative maculopathy. J Cataract Refract Surg. 2003 Sep;29(9):1800-10. doi: 10.1016/s0886-3350(03)00560-1.
citation: Moroi SE, Gottfredsdottir MS, Schteingart MT, Elner SG, Lee CM, Schertzer RM, Abrams GW, Johnson MW. Cystoid macular edema associated with latanoprost therapy in a case series of patients with glaucoma and ocular hypertension. Ophthalmology. 1999 May;106(5):1024-9. doi: 10.1016/S0161-6420(99)00528-X.
citation: Schumer RA, Camras CB, Mandahl AK. Latanoprost and cystoid macular edema: is there a causal relation? Curr Opin Ophthalmol. 2000 Apr;11(2):94-100. doi: 10.1097/00055735-200004000-00005.