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CTRI Number  CTRI/2018/04/012952 [Registered on: 03/04/2018] Trial Registered Retrospectively
Last Modified On: 06/07/2021
Post Graduate Thesis  Yes 
Type of Trial  Observational 
Type of Study   Prospective Uncontrolled Study 
Study Design  Other 
Public Title of Study   Retinal Disease 
Scientific Title of Study   Electroretinogram changes after AntiVEGF pharmacotherapy in patients with retinal vein occlusion. 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
28/2017  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Rose Mary George 
Designation  Secondary DNB Student 
Affiliation  Giridhar Eye Institute 
Address  Ponneth Temple Road Kadavanthra Cochin 682 020

Ernakulam
KERALA
682020
India 
Phone  9497625822  
Fax  04844000584  
Email  go2roseg@yahoo.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Rose Mary George 
Designation  Secondary DNB Student 
Affiliation  Giridhar Eye Institute 
Address  Ponneth Temple Road Kadavanthra Cochin 682 020

Ernakulam
KERALA
682020
India 
Phone  9497625822  
Fax  04844000584  
Email  go2roseg@yahoo.com  
 
Details of Contact Person
Public Query
 
Name  Dr Mahesh G 
Designation  Sr Consultant & HOD, Dept of Vitreo Retina 
Affiliation  Giridhar Eye Institute 
Address  Ponneth Temple Road Kadavanthra Cochin 682 020

Ernakulam
KERALA
682020
India 
Phone  9388467893  
Fax  04844000584  
Email  maheshgopalakrishnan@yahoo.com  
 
Source of Monetary or Material Support  
Giridhar Eye Institute 28 2576 Ponneth Temple Road Kadavanthra Cochin 682020 Kerala State 
 
Primary Sponsor  
Name  Giridhar Eye Institute 
Address  Plot No 28 2576 Ponneth Temple Road Kadavanthra Cochin 682 020 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Rose Mary George  Giridhar Eye Institute  Plot No. 28 2576 Ponneth Temple Road Kadavanthra Cochin 682 020
Ernakulam
KERALA 
9497625822
04844000584
go2roseg@yahoo.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Giridhar Eye Institute  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied
Modification(s)  
Health Type  Condition 
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  NIL  NIL 
Comparator Agent  NIL  NIL 
 
Inclusion Criteria  
Age From  30.00 Year(s)
Age To  85.00 Year(s)
Gender  Both 
Details  Patients diagnosed with RVO and has not taken any kind of treatment for the same are included in the study with a 6 months follow-up after AntiVEGF therapy 
 
ExclusionCriteria 
Details  (a) Intraocular surgery including cataract extraction within 6 months before enrolment (b) Co-existing other retinal diseases (c) Previous laser photocoagulation (d) Intravitreal injection of Triamcinolone acetenoid or antivascular endothelial growth factory (Anti-VEGF) agents (e) prior ocular inflammation. 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
To study the ERG changes before and after AntiVEGF pharmacotherapy in patients with retinal vein occlusion.  12 months from the date of enrolment 
 
Secondary Outcome  
Outcome  TimePoints 
Analysis of data for statistical record.  12 months from the date of enrolment 
 
Target Sample Size   Total Sample Size="20"
Sample Size from India="20" 
Final Enrollment numbers achieved (Total)= "18"
Final Enrollment numbers achieved (India)="18" 
Phase of Trial   Phase 3/ Phase 4 
Date of First Enrollment (India)   21/07/2017 
Date of Study Completion (India) 01/05/2018 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details
Modification(s)  
NO. THIS IS A DNB THESIS AND THE FINAL THESIS SUBMITTED TO NATIONAL BOARD OF EXAMINATIONS HAS BEEN ACCEPTED. 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

INTRODUCTION

Retinal vein occlusion (RVO) is the one of the most common retinal vascular disease; second to diabetic retinopathy. Central retinal vein occlusion (CRVO) results from thrombosis of the central retinal vein when it passes through the lamina cribrosa[i],[ii]. The characteristic features are disc oedema, increased dilatation and tortuosity of all retinal veins along with widespread deep and superficial haemorrhages, cotton wool spots, retinal oedema, and capillary non perfusion in all four quadrants of the retina. In less severe forms, the disc oedema may be absent. Branch retinal vein occlusion (BRVO) is caused by venous thrombosis at an arteriovenous crossing where an artery and vein share a common vascular sheath. [iii],[iv] .It has similar features to CRVO except that the findings are confined to that portion of the fundus drained by the affected vein.

Hemiretinal vein occlusion (HRVO) affects either the superior or inferior retinal hemisphere, and the retinal haemorrhages are nearly equal in two altitudinal quadrants (the nasal and temporal aspects) of the involved hemisphere.

The two main complications of RVO are macular oedema (MO), and retinal ischaemia leading to iris and retinal neovascularisation. Thrombosis of the retinal veins cause an increase in retinal capillary pressure resulting in increased capillary permeability and leakage of fluid and blood into the retina. Coexistent retinal ischaemia may exacerbate this process by the production of vascular endothelial growth factor (VEGF), which in turn promotes retinal capillary permeability and leakage into the extracellular space resulting in further development of MO. MO is the most common cause of visual impairment in RVO, followed by foveal ischaemia. The production of VEGF and other cytokines again promote new vessel formation involving the iris and angle in CRVO and the retina in BRVO. These complications may lead to neovascular glaucoma, vitreous haemorrhage, and tractional retinal detachment[v].

Anti-VEGF agents are now a popular choice for treatment of MO due to RVO based on the fact that VEGF-A is a key cytokine that mediates vascular leakage and causes MO in RVO. Intraocular VEGF levels are significantly high in CRVO.

Optical coherence tomography (OCT) is a non-invasive imaging technique, which uses light waves to take cross sectional pictures of retina. It is used to assess retinal thickness and morphology in CRVO patients with macular oedema.

Electroretinogram (ERG) is the record of changes in the resting potential of the eye induced by a flash of light. ERG is a graphical tracing of the summated action potentials generated in the retina in response to changes in retinal illumination.

 

Review of Literature

Retinal vein occlusion (RVO) leads to retinal ischemia, which then induces an upregulation of vascular endothelial growth factor (VEGF). Retinal vein occlusion (RVO) is a common retinal vascular disorder that is associated with an increase in the production of endothelial growth factor (VEGF) from the ischemic retina. The increased levels of VEGF is believed to lead to neovascularization of the iris (NVI) and/or anterior chamber angle and then progress to neovascular glaucoma (NVG).[vi],[vii]

Optical coherence tomography (OCT) is used to assess retinal thickness and morphology in CRVO patients with macular oedema, but it has been reported that a decrease of macular thickness was not associated with a corresponding improvement of vision, indicating that there is a dis­crepancy between OCT findings and the visual prognosis. Accordingly, an objective and reproducible measure of retinal function is needed to allow accurate assessment of the efficacy of treatment. Investigation of the correlation between functional and anatomic parameters could help to determine which parameters are relevant in this context, indicating that it is important to investigate the relation between retinal func­tion and morphologic changes in CRVO patients with macular oedema.

Electroretinography (ERG) is a non-invasive method that can be used to determine the degree of retinal ischemia, and this test can be performed repeatedly during the course of the

CRVO. The results of several studies have demonstrated that different components of the full-field ERGs, e.g., amplitudes of the b-wave, b/a-wave amplitude ratio, and the implicit times of the 30 Hz flicker ERGs, can be helpful in distinguishing the ischemic type from nonischemic type of CRVO. However, there is no report that showed whether these ERG parameters were significantly correlated with the intraocular VEGF level.

The electroretinogram (ERG) is an objective measure of retinal function, but there is controversy regarding which ERG parameter is most useful for monitoring patients with retinal vein occlusion.[viii],[ix] In patients with CRVO, many studies have shown that the full-field ERG, particularly the b-wave implicit time of the 30 Hz flicker ERG, is a good predictor of the development of neovascular glaucoma.[x],[xi]The cone a-wave, cone b-wave, and 30 Hz flicker of the ERG not only reflect macular function, but also retinal function. In animal models of branch retinal vein occlusion (BRVO), ERG studies have demonstrated moderate to severe functional deficits of the photoreceptor, bipolar, amacrine, and ganglion cells.[xii],[xiii]

It is seen that the implicit times of the flicker electroretinograms (ERGs) are significantly correlated with the degree of retinal ischaemia in eyes with central retinal vein occlusion (CRVO).The degree of retinal ischaemia can be monitored by repeated flicker ERG recordings before and after treatment. In Yasuda et al study of flicker electroretinograms before and after intravitreal ranibizumab injection in eyes with CRVO showed the mean implicit times of the flicker ERGs of the affected eyes recorded with the RETevalTM system were significantly longer than that of the fellow eyes. One month after the IV Ranibizumab, the implicit times of the flicker  ERGs of affected eyes were significantly shortened. The shortening of the implicit times of the flicker ERGs after the IV Ranibizumab indicates an improvement of retinal function after anti-VEGF therapy for CRVO eyes[xiv].

In the natural course of CRVO, neovascular glaucoma usually occur in the first 8 months; however, it has been reported that anti-VEGF therapy delays the neovascular complications

 

AIMS AND OBJECTIVES: 

Aim:

To study ERG changes before and after antiVEGF pharmacotherapy in patients with retinal vein occlusions

Objective:

To study ERG changes in patients with RVO after antiVEGF therapy.

To study the improvement in visual acuity in patients with RVO after antiVEGF therapy.

To study the OCT changes in patients with RVO after antiVEGF therapy.

To study the complications in patients with RVO after antiVEGF therapy.

MATERIALS AND METHODS:

This is a prospective, uncontrolled study that was conducted on patients with treatment naïve retinal vein occlusion.

Inclusion criteria

Patients diagnosed with RVO and has not taken any kind of treatment for the same are included in the study with a 6 month follow up after antiVEGF therapy.

The exclusion criteria are

 1) Intraocular surgery (including cataract extraction) within 6 months before enrolment,

 2) Coexisting other retinal diseases,

 3) Previous laser photocoagulation,

 4) Intravitreal injection of triamcinolone acetonide or antivascular endothelial growth factor (anti-VEGF) agents,

 5) Prior ocular inflammation,

                                                                                      

Study setting:

 Department of vitreoretinal surgery, Giridhar eye institute, Kadavantra, Kochi

 

Study Design:

 A prospective, uncontrolled study that is conducted on patients with retinal vein occlusion, presenting to us without any kind of treatment taken before, and is followed up till 6months after giving antiVEGF therapy.

 

Sample size:

The sample size was calculated using Single Mean - Paired t-test

Where  Î¼1 = Pre-test mean

μ2 = Post-test mean

σ 1 = Standard deviation in the pre-test

σ 2 = Standard deviation in the post-test

Δ = Effect size

α = Significance level

1-β = Power

Minimum Sample size required is 20 patients.

Methods:

All the included patients undergoes detailed ophthalmic evaluation with the following modalities

1) Detailed history taking

2) Vision testing

3) Slit-lamp examination and applanation tonometry

4) Dilated fundus examination

5) ERG

6) OCT

7) FFA in selected patients

Informed consent has to be taken from each selected participant.


REFERENCES

1.             Green WR, Chan CC, Hutchins GM, Terry JM. Central retinal vein occlusions: A prospective histopathologic study of 29 eyes in 28 cases. Retina 1981; 1: 27–55.

 

2.             Green WR. Retina. In: Spencer WH (ed). Ophthalmic pathology. An Atlas and Textbook. 3rd ed. WB Saunders: Philadelphia, 1985; p589

 

3.             Hockley DJ, Tripathi RC, Ashton N. Experimental retinal branch vein occlusion in the monkey. Histopathological and ultrastructural studies. Trans Ophthalmol Soc UK 1976; 96(2):202–209.

 

4.             Orth DH, Patz A. Retinal branch vein occlusion. Surv Ophthalmol 1978; 22: 357–376.

 

5.             Sivaprasad S, Amoaku WM, Hykin P; RVO Guideline Group The Royal College of Ophthalmologists Guidelines on retinal vein occlusions: executive summary. Eye (Lond).2015; 29: 1640

 

6.             Tripathi RC, Li J, Tripathi BJ, Chalam KV, Adamis AP. Increasedlevel of vascular endothelial growth factor in aqueous humor ofpatients with neovascular glaucoma. Ophthalmology.1998;105:232–237

 

7.              The Central Vein Occlusion Study Group. Natural history andclinical management of central retinal vein occlusion. Arch Oph-thalmol. 1997;115:486 – 491.5

8.             Hayreh SS, Klugman MR, Podhajsky P, Kolder HE. Electroretinography in central retinal vein occlusion. Correlation of electroretinographic changes with pupillary abnormalities. Graefes Arch Clin Exp Ophthalmol. 1989;227(6):549–561

9.             Williamson TH, Keating D, Bradnam M. Electroretinography of central retinal vein occlusion under scotopic and photopic conditions: what to measure? Acta Ophthalmol Scand. 1997;75(1):48–53.

10.         Larsson J, Andreasson S, Bauer B. Cone b-wave implicit time as an early predictor of rubeosis in central retinal vein occlusion. Am J Ophthalmol. 1998;125(2):247–249.

11.         Larsson J, Bauer B, Andréasson S. The 30-Hz flicker cone ERG for monitoring the early course of central retinal vein occlusion. Acta Ophthalmol Scand. 2000;78(2):187–190.

12.         Zhang Y, Fortune B, Atchaneeyasakul LO, et al. Natural history and histology in a rat model of laser-induced photothrombotic retinal vein occlusion. Curr Eye Res. 2008;33(4):365–376.

13.           Noma, H., Mimura, T., Kuse, M., & Shimada, K. (2014). Association of electroretinogram and morphological findings in central retinal vein occlusion with macular edema. Clinical Ophthalmology (Auckland, N.Z.), 8, 191–197.

 

14.         Yasuda, S., Kachi, S., Ueno et al;  Flicker electroretinograms before and after intravitreal ranibizumab injection in eyes with central retinal vein occlusion. Acta Ophthalmol, 2015.


 
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