Choroidal neovascularisation CNV PDT,TTT,MPC ALI. SALEHI MD

 CNV is an important cause of visual Impairment and may develop from more than 30 ocular diseases. The most common causes of CNV are  ARMD  Pathologic myopia

ARMD Non neovascular (Nonexudative) Non neovascular (Nonexudative) Neovascular (exudative) The hallmark of nonexudative form is drusen. The hallmark of neovascular is the presence of CNV.

Prevalence Is the most common cause of irreversible visual loss in the world in individuals over 50 years of age (1.7%) Age % of patients % >75 30%

 AMD is a major cause of visual impairment in the USA.  1.8 million Americans age 40 and older have advanced AMD and another 7.3 million people with intermediate AMD are at substantial risk for vision loss.  By 2020 there will be 2.9m people with advanced AMD.

 Nonneovascular changes with AMD can increase a break in bruch’s membrane.  neovascular tissue from choriocapillaris to perforate the outer aspect of BM.  These new vessels are accompanied by fibroblasts  Fibrovascular complex Proliferates within the inner aspect of BM.  CNV in the fovea is the major cause of severe central visual loss, in AMD

FA pattern of CNV  Classic CNV  Occult CNV o Classic CNV is an area of bright fairly uniform hyperflorscence identified in the early phase of the FA

 That progressively intensifies and with leakage of dye obscuring the boundaries of this area by the late phases. Occult CNV : (2Forms)  Fibrovascular PED  Late leakage of an undetermined source

3 terms are important :  Predominantly classic CNV  Minimally classic CNV  Occult CNV with no classic

Predominantly classic  Lesions where the CNV occupies more than 50% of the lesion, including contiguous blood, pigment, scar, and staining. Minimally classic  When the proportion of classic CNV occupies between 1-49% of the entire lesion. Occult with no classic CNV  there is no classic CNV in the lesion( only occult CNV)

Management of the neovascular form of AMD  Laser photocoagulation (thermal laser)  Photodynamic therapy (PDT)  T.T.T (Transpupillary Thermo Therapy)  Antiangiogenic drugs (Avastin,Lucentice)

 The benefits of laser (MPC) therapy have been shown only for classic CNV and the benefits of PDT only for lesions that are predominantly classic or purely occult CNV.

 Photocoagulation is used in the treatment of many retinal disease including: 1)Diabetic retinopathy 2)CNV 3)retinal vascular disease 4)sickle cell retinopathy 5)peripheral retinal tears

 Until the year 2000 the only available treatment for the more aggressive, wet form of AMD was laser photocoagulation.  It was used only in those patients with small well-defined lesions located outside the fovea.

 Laser light is mainly absorbed by 3 pigments 1)melanin2)hemoglobin3)xanthophyll

 Melanin strongly absorbs all ultraviolet and invisible wavelengths.  Hemoglobin has strong absorption in the violet (420nm) and green(514nm) wavelengths.  Xanthophylls which is the pigment most densely distributed in the macular area absorbs the blue wavelength (460nm)

 Laser application can affect tissue according to different interaction mode 1)Thermal (MPC,TTT) 2)Ionizing (YAG Capsulotomy) 3)Phothochemical (PDT)

 Laser photocoagulation uses a thermal (heat-producing) laser beam to cauterize abnormal blood vessels in the retina. ( abnormal scotoma). ( abnormal scotoma).  80-90% CNV due to AMD presents subfoveally that don’t benefit from MPC.

 Laser photocoagulation is the transfer of light energy into heat energy wavelength extend from 400nm which is blue light to 800nm which is the infrared wavelength.

 A rise in temperature of about 10c to 20c will cause coagulation of the ocular target tissue. The most common laser used for these Procedure is argon green light source.

 Patients with subfoveal lesion or juxtafoveal lesion so close to the foveal center that laser may damage the center of vision, needs to PDT

Photodynamic therapy with visudyne (verteporfin):  PDT selectively closes CNV, halting the progression and size of CNV lesions while slowing the loss of VA  In 2001 the FDA also approved visudyne for the treatment of pathologic myopia and ocular histoplasmosis

 PDT involves an IV injection of visudyne a photosensitizer, light- activated drug.  After infusion visudyne is selectively activated by illuminating a light from a non-thermal laser source at a wavelength (689nm )

Photochemical effect (PDT)  A chemical reaction can be made to occur by intense laser energy if the energy of the photons is high enough  Energizing of photons increases with shorter wavelengths therefore ultraviolet light is more effective in producing photochemical reaction than is visible or infrared light.

 The power of laser is not strong enough to cause any thermal damage to the retinal tissue.  Visudyne is a potent second- generation photosensitizer derived from porphyrin.  The molecule has along absorption wavelength with several peaks, including a strong absorption peak in the 688 to 692 nm region

 Visudyne absorb light at wavelengths around 690nm (red light), which can penetrate blood, melanin and fibrotic tissue.  When visudyne is activated by light in the presence of oxygen, highly reactive, oxygen short-lived singlet and reactive oxygen radicals are generated.

 Light activation of visudyne Results in local damage to neovascular endothelium, resulting in vessel occlusion. ( Platelet aggregation, fibrin clot formation and vasoconstriction). ( Platelet aggregation, fibrin clot formation and vasoconstriction). Visudyne is indicated :  Predominantly classic subfoveal CNV due to ADM  Pathologic myopia  POHS

The most frequently adverse events (10-30% incidence) were : (10-30% incidence) were :  Site reactions (extravasations- rash)  Blurred vision  Decreased VA  Visual field defect

 Hyperthermia Is the process whereby the laser causes an elevated tissue temperature above the normal 37c But still avoids coagulation. This temperature generally ranges between 42c and 52c.

 At these temperature bimolecular undergo changes that may result in significant membrane alteration.  If this type of hyperthermia is maintained for a period of time (20 seconds to 3 to 4 minutes) irreversible effects occur.  Hyperthermia T.T.T

T.T.T  Is a technique in which heat is delivered to the choroid and RPE through the pupil using a modified diode laser.  This laser technique contrast with the laser used in standard MPC in that T.T.T uses a lower power laser for more prolonged periods of time and is designed to gently heat the choroidal lesion, thus limiting damage to the overlying RPE.

The use of T.T.T to treat  Subfoveal CNV  Choroidal melanoma  Retinoblastoma The goal is to stop the growth and leakage of the new blood vessels and preserve vision.

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