Electroretinogram changes after AntiVEGF pharmacotherapy in patients with retinal vein occlusion.

INTRODUCTION

Retinalvein occlusion (RVO) is the one of the most common retinal vascular disease;second to diabetic retinopathy. Central retinal vein occlusion (CRVO) resultsfrom thrombosis of the central retinal vein when it passes through the lamina cribrosa[i],[ii].The characteristic features are disc oedema, increased dilatation andtortuosity of all retinal veins along with widespread deep and superficialhaemorrhages, cotton wool spots, retinal oedema, and capillary non perfusion inall 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 anarteriovenous 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 thatportion of the fundus drained by the affected vein.

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

Thetwo main complications of RVO are macular oedema (MO), and retinal ischaemialeading to iris and retinal neovascularisation. Thrombosis of the retinal veinscause an increase in retinal capillary pressure resulting in increased capillarypermeability and leakage of fluid and blood into the retina. Coexistent retinalischaemia may exacerbate this process by the production of vascular endothelialgrowth factor (VEGF), which in turn promotes retinal capillary permeability andleakage into the extracellular space resulting in further development of MO. MOis the most common cause of visual impairment in RVO, followed by fovealischaemia. The production of VEGF and other cytokines again promote new vesselformation involving the iris and angle in CRVO and the retina in BRVO. Thesecomplications may lead to neovascular glaucoma, vitreous haemorrhage, andtractional retinal detachment[v].

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

Opticalcoherence tomography (OCT) is a non-invasive imaging technique, which useslight waves to take cross sectional pictures of retina. Itis used to assess retinal thickness and morphology in CRVO patients withmacular oedema.

Electroretinogram(ERG) is the record of changes in the resting potential of the eye induced by aflash of light. ERG is a graphical tracing of the summated action potentialsgenerated 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 vascularendothelial growth factor (VEGF). Retinal vein occlusion (RVO) is a common retinalvascular disorder that is associated with an increase in the production ofendothelial growth factor (VEGF) from the ischemic retina. The increased levelsof VEGF is believed to lead to neovascularization of the iris (NVI) and/oranterior chamber angle and then progress to neovascular glaucoma (NVG).[vi],[vii]

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

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

CRVO. The resultsof several studies have demonstrated that different components of the full-fieldERGs, e.g., amplitudes of the b-wave, b/a-wave amplitude ratio, and theimplicit times of the 30 Hz flicker ERGs, can be helpful in distinguishing the ischemictype from nonischemic type of CRVO. However, there is no report that showedwhether these ERG parameters were significantly correlated with the intraocularVEGF level.

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

It is seen thatthe implicit times of the flicker electroretinograms (ERGs) are significantly correlated withthe degree of retinal ischaemia in eyes with central retinal vein occlusion (CRVO).Thedegree of retinal ischaemia can be monitored by repeated flicker ERG recordingsbefore and after treatment. In Yasuda et al study of flicker electroretinogramsbefore and after intravitreal ranibizumab injection in eyes with CRVO showed themean implicit times of the flicker ERGs of the affected eyes recorded with theRETevalTM system were significantly longer than that of the fellow eyes. Onemonth after the IV Ranibizumab, the implicit times of the flicker  ERGs of affected eyes were significantlyshortened. The shortening of the implicit times of the flicker ERGs after theIV Ranibizumab indicates an improvement of retinal function after anti-VEGFtherapy for CRVO eyes[xiv].

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

AIMSAND OBJECTIVES:

Aim:

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

Objective:

To study ERGchanges in patients with RVO after antiVEGF therapy.

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

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

To study thecomplications in patients with RVO after antiVEGF therapy.

MATERIALS AND METHODS:

Thisis a prospective, uncontrolled study that was conducted on patients with treatmentnaïve retinal vein occlusion.

Inclusion criteria

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

The exclusion criteria are

1. Intraocular surgery (including cataractextraction) within 6 months before enrolment,

2. Coexisting other retinal diseases,

3. Previous laser photocoagulation,

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

5. Prior ocular inflammation,

                                                                                       Study setting:

Department of vitreoretinal surgery, Giridhareye institute, Kadavantra, Kochi

 Study Design:

A prospective, uncontrolled study that is conductedon patients with retinal vein occlusion, presenting to us without any kind oftreatment taken before, and is followed up till 6months after giving antiVEGFtherapy.

 Sample size:

The sample sizewas calculated using Single Mean - Paired t-test

Where  Î¼1 = Pre-test mean

μ2 = Post-testmean

σ 1 = Standarddeviation in the pre-test

σ 2 = Standarddeviation in the post-test

Δ = Effect size

α = Significancelevel

1-β= Power

MinimumSample size required is 20 patients.

Methods:

Allthe included patients undergoes detailed ophthalmic evaluation with thefollowing modalities

1. Detailedhistory taking

2. Visiontesting

3. Slit-lampexamination and applanation tonometry

4. Dilatedfundus examination

5. ERG

6. OCT

7. FFAin selected patients

Informedconsent has to be taken from each selected participant.

REFERENCES

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10.        Larsson J, Andreasson S, Bauer B. Cone b-wave implicit time as an earlypredictor 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 formonitoring the early course of central retinal vein occlusion. ActaOphthalmol Scand. 2000;78(2):187–190.

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

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

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