CNV updates

What’s New in CNVCNV

Mohamed ELShafieAssistant lecturer of

ophthalmologyKafr ELShiekh university

CNVCNV

CNV

Growth of abnormal

blood vessels in the choroidal

layers, these abnormal vessels

can rupture the retinal layers

causing deterioration of vision

at the affected regions

Risk factorRisk factor

A- Personal risk factors: A- Personal risk factors: ARMD, pathologic myopia, lightly pigmented populations, higher BMI, family history,.. ect

Risk factor B- Environmental and nutritional risk factors: B- Environmental and nutritional risk factors: smoking, light exposure, cataract surgery, dietry fat intake.

C-Systemic diseases:C-Systemic diseases: HTN, DM & others i.e CVD

Clinical PictureClinical Picture

SymptomsSymptoms

SignsSigns

Loss of central vision, visual distortion, Loss of central vision, visual distortion, visual field defects, loss of contrast visual field defects, loss of contrast

sensitivitysensitivity . .

Hemorrhage, macular edema, subretinalHemorrhage, macular edema, subretinalfluid, PED, chorioretinal folds.fluid, PED, chorioretinal folds.

Clinical investigation of Clinical investigation of CNVCNV

OCTOCTFAFA

Angiographic classification of CNVAngiographic classification of CNV..

Type 1 Choroidal Neovascularization ( occult ) : Type 1 Choroidal Neovascularization ( occult ) :

Early stages are Early stages are poorly delineated poorly delineated with fluoresceinwith fluorescein Late stages are stained with irregular margins.Late stages are stained with irregular margins.

Angiographic classification of CNVAngiographic classification of CNV..

Type 2 choroidal Neovascularization (classic) : Type 2 choroidal Neovascularization (classic) :  

Early fluorescein angiogram its seen as Early fluorescein angiogram its seen as well delineated well delineated vascular patternvascular pattern..

Late stages it stained with indistinct Late stages it stained with indistinct margins.margins.

Assessment of CNV by OCT.

Differentiation between types of CNVDifferentiation between types of CNV

OCT measurement of macular thicknessOCT measurement of macular thickness

Differentiation between types of CNVDifferentiation between types of CNV

Showing disrupted reflections from (RPE/choriocapillaris) with poorly defined boundaries.

Showing disrupted reflections from (RPE/choriocapillaris) with well-defined boundaries.

Occult Occult CNVCNV

Classic Classic CNVCNV

Comparison between OCT & FA in detection of macular Comparison between OCT & FA in detection of macular oedemaoedema

OCT (n =

46)FA (n = 46)

P

No % No %

Diffuse28 60.9 20 43.5

<0.001

*

Cystoid18 39.1 8 17.4

Insignificant or no

leak

0 0 18 39.1*Significant P < 0.05

Study included Study included 46 eyes of 38 patients attending

the outpatient clinics of Mansoura ophthalmic center.the outpatient clinics of Mansoura ophthalmic center.

What’s New in TTTWhat’s New in TTT

10. Topical Pazopanib

• Csaky (2015):– Multicenter, 1yr, Phase 2b RCT of 510 patients

with subfoveal CNV secondary to AMD– Lucentis given as-needed to patients taking drops

–Pazopanib is not effective in reducing treatment burden of Lucentis

Csaky, et al. Ophthalmology 2015;122:579Csaky, et al. Ophthalmology 2015;122:579

Pazopanib did not significantly reduce the need for Lucentis injections (primary outcome)

What’s New in AMDWhat’s New in AMD

9. Implantable Miniature Telescope10. Drug Pipeline

• The FDA approved in 2010 for patients 75yrs and older with stable severe-to-profound vision impairment caused by bilateral end-stage AMD.

• Marketed as CentraSight

Implantable Miniature Telescope

Retinal Prosthesis

FDA grants Argus II retinal prosthesis from Second Sight, Inc “compassionate use” status for severe end-stage RP

Retinal ProsthesisRunner-U

p

What’s New in AMDWhat’s New in AMD

8. Aspirin9. Implantable Miniature Telescope10. Drug Pipeline

• Prevent of cardiovascular events, reduce the risk of some cancers, reduced risk of Alzheimer's disease.

• Adverse effects of aspirin – Gastrointestinal hemorrhage,

worsen hypertension, renal failure, aggravate asthma, hemorrhagic stroke

– Each year 16,500 deaths are related to aspirin and NSAID use

Seshasai SR, et al. Arch Intern Med. 2012;172:209-16

Aspirin & CNVHarmful Effect

Feman (1972)Bloome (1978)Kingham (1988)

Lewis (1988)AREDS (2000)Klein (2012)

de Jong (2012)Cheung (2013)

Liew (2013)Ye (2014)

No EffectMPS Group (1986)MPS Group (1990)

Klein (1991)Hirvela (1996)Klein (2001)

Douglas (2007)Rudnicka (2010)

Protective EffectChristen (2001)Christen (2009)

What’s New in AMDWhat’s New in AMD

7. Lifestyle8. Aspirin9. Implantable Miniature Telescope10. Drug Pipeline

What’s Good for the Heart

Is also Good for the Eye!

Lose weightDon’t smoke

Exercise regularly– Gopinath (2015): No significant difference in 10yr

smoking cessation rates between smokers with and without AMD (AMD: 25%, non-AMD: 20%)

-Munch (2013): Being physically active ≥7hrs/wk decreased the risk of large drusen compared to 0-2 hrs/wk

What’s New in AMDWhat’s New in AMD

6. Sunlight7. Lifestyle8. Aspirin9. Implantable Miniature Telescope10. Drug Pipeline

• Delcourt (2014): Individuals with the highest and lowest exposure levels were at increased risk of early AMD compared with medium exposure.

- The adult lens absorbs nearly 100% of light below 400nm–Cataract surgery results in increased exposure to short-wavelength light and this may increase the risk of photochemical damage to the retina–Inconsistent association with AMD risk

Runner-Up

Kessel (2015): Surgery did not increase risk of progression to CNV within 6-12 months Recommend patients with AMD and visually significant cataract are offered cataract surgery

What’s New in AMDWhat’s New in AMD

5. Lutein6. Sunlight7. Lifestyle8. Aspirin9. Implantable Miniature Telescope10. Drug Pipeline

• Macular Pigment– Lutein and zeaxanthin are the major components of

macular pigment– Macular pigment may protect the retina from

photochemical damage by absorbing blue light.

• Lutein supplementation may decrease the risk of AMD progression

in persons with low dietary intake.

What’s New in AMDWhat’s New in AMD

4. Fish5. Lutein6. Sunlight7. Lifestyle8. Aspirin9. Implantable Miniature Telescope10. Drug Pipeline

• Fish oil is rich in omega-3 long-chainpolyunsaturated fatty acids (LCPUFA).

• Christen (2011)– Consumption of 1 or more of fish per week associated with a 40% lower risk of developing CNV.

What’s New in AMDWhat’s New in AMD

3. Anti-VEGF medications4. Fish5. Lutein6. Sunlight7. Lifestyle8. Aspirin9. Implantable Miniature Telescope10. Drug Pipeline

• Which is better: Lucentis or Avastin?– Both drugs have the same mechanism of action,

but very different structures– Lucentis is much more expensive than Avastin

• Dosing regimens– Monthly dosing produces best outcomes but has

greatest treatment burden– Treat and extend currently most popular strategy

–Visual results of Avastin were equivalent to Lucentis at both monthly and PRN dosing

-Lucentis produced greater decreases in macular thickness at both monthly and PRN dosing.

-Serious systemic adverse events were more frequent with Avastin than with Lucentis

–Mean gain in vision was greater with monthly dosing vs PRN dosing for both drugs

Aflibercept (Eylea)• Recombinant fusion protein • Be approved by the FDA for treating patients

with CNV (2011).• The recommended dose for EYLEA is 2 mg

monthly for 3 months, followed by injection once every 2 months.

What’s New in AMDWhat’s New in AMD

2. Genetics3. Anti-VEGF medications4. Fish5. Lutein6. Sunlight and Cataract Surgery7. Lifestyle8. Aspirin9. Implantable Miniature Telescope10. Drug Pipeline

– Attempts to predict the risk of developing advanced AMD .

– Determine response to medication.

Genetic testing services use risk models to calculate your Genetic testing services use risk models to calculate your risk of contracting various disorders based on genotyperisk of contracting various disorders based on genotype

Shastry BS. Discovery Medicine. Aug 2011Shastry BS. Discovery Medicine. Aug 2011

What’s New in AMDWhat’s New in AMD1. Vitamins2. Genetics3. Anti-VEGF medications4. Fish5. Lutein6. Sunlight7. Lifestyle8. Aspirin9. Implantable Miniature Telescope10. Drug Pipeline

• Vitamin D:– Has antiangiogenic, antioxidant and anti-inflammatory

effects

– Itty (2014): Vitamin D deficiency is a potentially modifiable risk factor for the development of CNV.

• B vitamins:– Capable of significantly lowering serum levels of

homocysteine

–Gopinath (2013): Taking vitamin B supplements decreased risk of developing AMD by 47%

What’s New in AMDWhat’s New in AMD1. Vitamins2. Genetics3. Anti-VEGF medications4. Fish5. Lutein6. Sunlight7. Lifestyle8. Aspirin9. Implantable Miniature Telescope10. Drug Pipeline

Thank You!Thank You!