53 Comments

Chapter 218 – Optic Nerve Blood Flow Measurement

Chapter 218 – Optic Nerve Blood Flow Measurement

 

COLM O’BRIEN

ALON HARRIS

 

INTRODUCTION

The fact that a substantial number of glaucoma patients (perhaps up to 30%) have normal intraocular pressure (IOP) at the time of initial diagnosis indicates that risk factors other than IOP alone contribute to the pathogenesis of optic nerve damage in this disorder. Foremost among the proposed risk factors is ischemia contributing to the loss of optic nerve axons, a concept recognized for more than 100 years. It has become increasingly clear that vascular compromise also plays a significant role in high-pressure glaucoma. Some clinical features point to an underlying vascular problem; these include localized rim notching or focal ischemic glaucoma ( Fig. 218-1 ), peripapillary vasoconstriction ( Fig. 218-2 ), optic disc hemorrhage ( Fig. 218-3 ), and senile sclerotic optic discs with peripapillary choroidal sclerosis ( Fig. 218-4 ).[1] [2]

The precise role of optic nerve blood flow in the loss of axons in glaucoma is not clear. An acute cessation of flow in a short posterior ciliary artery, such as occurs in giant cell arteritis, results in pallor and gross visual loss but little cupping of the optic disc. Focal ischemia (which presumably arises from infarction of a small ciliary vessel in the prelaminar region) produces localized disc cupping and pallor and a corresponding, well-defined (frequently small) visual field defect. Although several studies have recorded vascular changes in glaucoma, it is not clear whether these findings are primary causative events or whether they occur secondary to loss of neural tissue. Long-term studies are needed to address this issue. Further research into the macro- and microcirculations of the ocular and optic nerves will help elucidate the relative roles of IOP and ischemia in the pathogenesis of glaucoma.

APPLIED ANATOMY

The ophthalmic artery, which is the first branch of the internal carotid artery, gives off 2–4 posterior ciliary arteries (PCAs), which later divide into 10–20 short PCAs that pierce the sclera and enter the globe around the optic nerve. The number of short PCAs is variable, as is the course they take in this region, but in general they supply the posterior choroid and anterior optic nerve either directly or indirectly via the arterial circle of Zinn-Haller, which, when present, is formed by the anastomosis of the medial and lateral short PCAs. [3] [4] The central retinal artery, which enters the optic nerve about 8–12?mm behind the globe, passes along the central axis of the nerve and gives off few, if any, branches to the neural tissue. Venous drainage of the anterior optic nerve is to the central retinal vein and later the superior ophthalmic vein.

The anterior optic nerve head (prelaminar, laminar, and postlaminar neural tissue) is supplied by branches from the short PCA, and the nerve fiber layer of the superficial retina receives arteriolar branches from the central retinal artery. The capillaries of the anterior optic nerve head (retinal and ciliary) have tight junctions, are not fenestrated, and form a rich anastomotic

 

 

Figure 218-1 Focal ischemic optic disc appearance (left eye). Localized loss of the superotemporal neuroretinal rim in a 54-year-old woman who has migraine and Raynaud’s phenomenon.

 

 

Figure 218-2 Peripapillary vasoconstriction in glaucoma (right eye). Marked narrowing of a branch of the inferotemporal retinal artery (at the 6 o’clock position) as it crosses the optic disc boundary adjacent to the inferior temporal vein.

plexus. Histological examination of glaucomatous optic nerves shows a reduction in the number of capillaries, consistent with the degree of neural loss.

The contribution of the peripapillary choroidal circulation to the perfusion of the anterior optic nerve head remains unclear, although watershed zones in the region of the optic nerve that arise from the presence of choroidal end-arteries may be a factor in the development of optic nerve ischemia.[4] Some investigators consider that the true “watershed” lies in the division of the

 

1471

 

 

Figure 218-3 Optic disc hemorrhage (right eye). Flame-shaped hemorrhage adjacent to an acquired optic nerve pit at the 6 o’clock position.

 

 

Figure 218-4 Senile sclerotic (“moth-eaten”) optic disc (left eye). The pale disc has a shallow, saucerized optic cup and peripapillary choroidal sclerosis. There is a small, flame-shaped disc hemorrhage at the 2 o’clock position.

short PCAs into branches that supply the choroid and branches that supply the optic nerve head.

PHYSIOLOGY

Blood flow in the anterior optic nerve depends on many factors, which include the perfusion pressure (mean arterial blood pressure minus IOP) and the resistance to flow as determined by the vascular caliber in the arterioles and capillaries.[5] The latter is influenced by factors that affect local tissue blood flow (e.g., metabolic, endothelial). The ability to keep local tissue flow constant and counteract changes in the local metabolic environment is called autoregulation.[5] [6] Moderate increments in IOP and systemic blood pressure have little effect on anterior optic nerve blood flow, and autoregulatory mechanisms maintain flow in hyperoxic and hypercapnic conditions. However, if autoregulation is impaired, elevated IOP may reduce optic nerve perfusion; optic nerve and retinal circulations have deficient autoregulation in normal-pressure and primary open-angle glaucoma. An ocular diastolic perfusion pressure less than 35?mmHg (4.7?kPa) is associated with a significant increase in the prevalence of glaucoma.[7]

Substances produced by the vascular endothelium play a major role in the control of ocular blood flow[8] ; these include the

 

 

Figure 218-5 Color Doppler imaging of the ophthalmic artery. Shown is the pulsatile spectral analysis with a sharp rise in the peak systolic velocity and a gradual tail-off to the end diastolic velocity at the end of each pulse waveform. Note the dicrotic notch within the diastolic phase.

vasodilators nitric oxide and prostacyclin and vasoconstrictors such as angiotensin and the endothelins. Cells that produce these substances have been identified in the choroid, retina, and optic nerve. Repeated endothelin-1 injections into the perineural space of the optic nerve produce chronic ischemia and excavation of the optic disc in animal studies.[9]

Although autonomic a- and ß-receptors have been identified in the optic nerve head, they do not appear to have any functional properties.

EXPERIMENTAL INVESTIGATIONS

Blood flow in the optic nerve head has been quantified in animal work using radiolabeled microsphere and iodoantipyrine methods, which show high flow in the prelaminar and laminar regions.[10] [11] In the retina and optic nerve, blood flow is coupled closely with glucose consumption, as measured by the deoxyglucose uptake technique. In monkeys, IOP raised above systolic blood pressure results in complete cessation of blood flow in the prelaminar tissue.

CLINICAL STUDIES

The anatomical regions of particular interest in glaucoma include the capillary plexus of the superficial retinal fiber layer, the pre- and intralaminar optic nerve head, and the peripapillary choroid. Currently, no single examination technique can be used to study all these vascular beds simultaneously.

Angiography

Both fluorescein and indocyanine green angiography (photographic, video, and scanning laser) are used to study the retinal, choroidal, and optic disc circulation. Fluorescein filling defects in the superficial part of the optic disc and choroid, delayed arm-to-retina and retinal artery and venous filling times, prolonged arteriovenous passage time, and reduced velocity in the retinal circulation have been described.[12]

Color Doppler Imaging

Blood flow velocities in the major ocular vessels (ophthalmic, central retinal, and short posterior ciliary arteries) can be measured using color-coded ultrasound Doppler instruments ( Fig. 218-5 ). Reduced velocity (particularly the end-diastolic component) and increased resistance to flow occur in all these vessels

 

1472

 

 

Figure 218-6 The ocular pressure pulse curve. Continuous recording of intraocular pressure produces a characteristic waveform pattern.

in both high and normal pressure open-angle glaucoma.[13] [14] Current color Doppler imaging (CDI) cannot measure absolute volume flow because they do not measure vessel diameter. However, a recently developed analysis technique incorporated in the CDI machine is now capable of determining the ophthalmic artery diameter.[15] Therefore, with this technique, ophthalmic artery volumetric blood flow can be assessed. Future developments may allow us to extend the ability of this technique to measure the central retinal artery diameter.

Laser Doppler Flowmetry

Both single-point and wide-field 10° scanning laser Doppler techniques have been used to study red blood cell movement in the capillary network in the anterior optic nerve head and peripapillary retinal circulation. The data show reduced blood flow velocities in the lamina cribrosa and in the nasal and temporal neural rim and retina in glaucoma.[16] The precise site and depth of measurement using these techniques remain unclear, although the approach itself evaluates the region of greatest interest in the pathogenesis of optic nerve damage in glaucoma.

Ocular Pulse Amplitude

Continuous recording of the change in IOP resulting from the change in ocular volume with the arrival of each bolus of blood at the eye gives a record of the ocular pressure pulse wave ( Fig. 218-6 ). By comparison with known ocular pressure–volume curves, a measure of the pulsatile component of ocular blood flow is derived; this is assumed to correspond to choroidal blood flow, because the greater part (approximately 90%) of total ocular flow is to the choroidal circulation. Reduced ocular pulse amplitude and pulsatile ocular blood flow occur in high- and normal-pressure glaucoma,[17] although the relevance of these findings to circulation in the optic nerve head is uncertain.

Ocular Blood Flow and Visual Field Loss

The number and size of optic disc fluorescein angiography filling defects increase with the severity of visual field loss in glaucoma. Delayed retinal and choroidal fluorescein filling times occur in high- and normal-pressure glaucoma and are related to the severity of the disease. CDI studies show reduced blood flow velocity in the short PCA, which corresponds with the location of visual field loss. Progressive visual field loss occurs in glaucoma patients who have the slowest blood flow velocity and the greatest resistance to flow.

SYSTEMIC VASCULAR DISEASE AND GLAUCOMA

It has been recognized for many years that glaucoma patients have a higher prevalence of concomitant vascular disease than do the rest of the population, which is particularly true of normal-pressure glaucoma. The more common problems include cardiac disease (angina), systemic hypertension and hypotension, small vessel disease (as occurs in atherosclerosis and diabetes mellitus), and cerebrovascular disease. In addition, the presence of systemic vasospastic conditions, such as Raynaud’s phenomenon and migraine, is relatively common in normal-pressure glaucoma. Patients affected by progressive glaucoma show significant nocturnal systemic hypotension (“dippers”) when ambulatory blood pressure is monitored for 24 hours, [18] but this may on occasion be the consequence of overzealous management of systemic hypertension. Elevated blood and plasma viscosity, increased platelet and red blood cell aggregation, increased red cell deformability, and activation of the coagulation cascade[19] have been reported in glaucoma.

The concept of vasospasm was introduced into the glaucoma literature recently, particularly for normal-pressure disease.[20] Implied is an abnormal vascular endothelial responsiveness (with normal anatomy) to common everyday stimuli such as cold, stress, and anxiety. Many patients exhibit a Raynaud-like peripheral circulation, with reduced finger flow after immersion of the hand in cold water. Migraine and silent myocardial ischemia appear to be more prevalent, and elevated systemic levels of the potent endothelial vasoconstrictor endothelin-1 have been reported in normal-pressure glaucoma. Precisely how these findings contribute to optic nerve head ischemia remains unclear.

Therefore, for every glaucoma patient, it is important that the ophthalmologist obtain an accurate history of systemic diseases, particularly cardiovascular problems, as well as the systemic medications being taken. Many cardiovascular drugs have effects on the eye, including systemic beta blockers (which have an ocular hypotensive effect). Obtaining an accurate systemic and medication history is clearly important at the time of diagnosis, and it is essential that this information be updated at each clinic visit.

 

1473

PHARMACOLOGY

When reduced ocular and optic nerve blood flow contributes significantly to the pathogenesis of axonal loss, modification of blood flow might provide protection from ischemia-induced neuronal damage. In vitro animal myography studies of isolated segments of the ophthalmic and ciliary arteries demonstrate that endothelin-l produces potent constriction, which can be prevented by voltage-gated calcium channel blockade.[21] Evidence exists that calcium antagonists, administered orally for concomitant systemic vascular disease, are associated with improved preservation of the visual field in some, but not all, normal-pressure glaucoma patients.[22] Similarly, some patients show improvement in ocular blood flow and contrast sensitivity with calcium channel blockers or inhaled carbon dioxide in short-term investigations. Medical and surgical reduction of IOP may, in some glaucoma patients, improve ocular blood flow.[23] Whether improved perfusion has any beneficial long-term effect on the visual field remains unclear.

 

 

REFERENCES

 

1. Geijssen HC, Greve EL. The spectrum of primary open angle glaucoma. Senile sclerotic glaucoma versus high tension glaucoma. Ophthalmic Surg. 1987;18:207–13.

 

2. Nicolela MT, Drance SM. Various glaucomatous optic nerve appearances: clinical correlations. Ophthalmology. 1996;103:640–9.

 

3. Lieberman MF, Maumenee AE, Green WR. Histological studies of the vasculature of the anterior optic nerve. Am J Ophthalmol. 1976;82:405–11.

 

4. Hayreh SS. Structure and blood supply of the optic nerve. In: Heilmann K, Richardson KT, eds. Glaucoma: conceptions of a disease. Stuttgart: Thieme; 1978:78–92.

 

5. Bill A. Vascular physiology of the optic nerve. In: Varma R, Spaeth GL, eds. The optic nerve in glaucoma. Philadelphia: JB Lippincott; 1993:37–50.

 

6. Anderson DR. Autoregulation in glaucoma. In: Drance SM, ed. International symposium on glaucoma, ocular blood flow and drug treatment. Baltimore: Williams & Wilkins; 1991:82–9.

 

7. Tielsch JM, Katz J, Sommer A, et al. Hypertension, perfusion pressure and primary open-angle glaucoma. Arch Ophthalmol. 1995;113:216–21.

 

8. Haefliger IO, Meyer P, Flammer J, Luscher TF. The vascular endothelium as a regulator of the ocular circulation: a new concept in ophthalmology? Surv Ophthalmol. 1994;39:123–32.

 

9. Orgul S, Cioffi GA, Wilson DJ, et al. An endothelin-1 induced model of optic nerve ischaemia in the rabbit. Invest Ophthalmol Vis Sci. 1996;37:1860–9.

 

10. Geijer C, Bill A. Effect of raised intraocular pressure on retinal, prelaminar and retrolaminar optic nerve blood flow in monkeys. Invest Ophthalmol. 1979;18: 1030–42.

 

11. Sperber GO, Bill A. Blood flow in glucose consumption in the optic nerve, retina and brain: effects of high intraocular pressure. Exp Eye Res. 1985;639:41–8.

 

12. Schwartz B, Nagin P. Fluorescein angiography of the optic disc. In: Varma R, Spaeth GL, eds. The optic nerve in glaucoma. Philadelphia: JB Lippincott; 1993:307–24.

 

13. Harris A, Sergott RC, Spaeth GL, et al. Color Doppler analysis of ocular vessel blood velocity in normal-tension glaucoma. Am J Ophthalmol. 1994;118:642–9.

 

14. Rankin SJA, Walman BE, Buckley AR, Drance SM. Color Doppler imaging and spectral analysis of the optic nerve vasculature in glaucoma. Am J Ophthalmol. 1995;119:685–93.

 

15. Orge F, Harris A, Kagemann L, et al. The first technique for non-invasive measurements of volumetric ophthalmic artery blood flow in humans. Br J Ophthalmol. 2002;86(11):1216–9.

 

16. Michaelson G, Longhans MJ, Groh MJM. Perfusion of the juxta-papillary retina and neuroretinal rim in primary open angle glaucoma. J Glaucoma. 1996;5:91–8.

 

17. James CB, Smith SE. Pulsatile ocular blood flow in patients with low tension glaucoma. Br J Ophthalmol. 1991;75:466–70.

 

18. Graham SL, Drance SM, Wijsman K, et al. Ambulatory blood pressure monitoring in glaucoma. The nocturnal dip. Ophthalmology. 1995;102:61–9.

 

19. O’Brien C, Butt Z, Ludlow C, Detkova P. Activation of the coagulation cascade in untreated primary open angle glaucoma. Ophthalmology. 1997;104:725–30.

 

20. Flammer J. To what extent are vascular factors involved in the pathogenesis of glaucoma? In: Kaiser HJ, Flammer J, Hendrickson P, eds. Ocular blood flow. Basel: Karger; 1996:12–39.

 

21. Meyer P, Haefliger IO, Flammer J, Luscher TF. Endothelium dependent regulation in ocular vessels. In: Kaiser HJ, Flammer J, Hendrickson P, eds. Ocular blood flow. Basel: Karger; 1996:64–73.

 

22. Kitazawa Y, Shirai H, Go FJ. The effect of calcium antagonist on visual field in low tension glaucoma. Graefes Arch Clin Exp Ophthalmol. 1989;227:408–12.

 

23. Harris A, Spaeth GR, Sergott RC, et al. Retrobulbar hemodynamic effects of betaxalol and timolol in normal tension glaucoma. Am J Ophthalmol. 1995; 120:168–75.

Advertisements

53 comments on “Chapter 218 – Optic Nerve Blood Flow Measurement

  1. You post informative posts Just bookmarked !!!

  2. greetings. perform i must utilize actual sweetie combined with water to drink about the head or about the locks? which are the biotin that contains shampoos? as well as that make of locks natural oils usually are secure to utilise? thanks.

  3. Well accomplished, whilst you will look for dietary supplements available that may be advantageous within supplying some extra antioxidant safety, absolutely nothing even even compares to eating antioxidant-rich fruits and veggies within their organic form. Dietary supplements are simply what their own title claims: SUPPLEMENTS- not really substitutes.

  4. http://paydayloanholiday.com payday loan how it works payday loans online interest rate on payday loan
    payday advance problems

  5. http://paydayloanholiday.com payday calculator payday cash loan payday loans with low interest
    payday loans santa barbara

  6. http://genericcialisonlineph.com/ tadalafil generic vs cialis Cialis Pills buy cialis generic online
    compare cialis generic viagra

  7. http://genericcialisonlineph.com/ canada cialis generic maintain an erection Cheap Cialis viagra pill for sale cialis generic
    generic cialis problems

  8. http://genericcialisonlineph.com/ can u buy viagra over the counter cialis generic Cheap Generic Cialis viagra average age cialis generic
    cialis india generic

  9. http://propeciafd.com/ proscar pill cutter finasteride 5mg generic propecia pill cutter finasteride 5mg
    generic propecia effective leading

  10. http://propeciafd.com/ generic propecia india propecia online generic propecia india
    merck finasteride 5mg

  11. http://propeciafd.com/ propecia or generic finasteride order propecia every other day propecia finasteride
    finasteride minoxidil combination

  12. http://cialissafepharmacy.com/ buy tadalafil china buy cialis online viagra average age cialis generic
    generic cialis tadalafil sildenafil citrate

  13. http://cialissafepharmacy.com/ buy generic cialis computer generic Tadalafil generic cialis tadalafil
    purchase cialis generic viagra

  14. http://propeciasafepharmacy.com/ price generic propecia lowest prices cheap propecia prevacid reditabs generic finasteride
    sam e hair loss finasteride

  15. http://propeciasafepharmacy.com/ proscar 5 mg generic finasteride buy propecia online buy finasteride 5mg generic propecia
    generic propecia best

  16. http://propeciasafepharmacy.com/ finasteride propecia side effects order propecia pless finasteride
    generic finasteride 1 megagram

  17. http://propeciasafepharmacy.com/ split finasteride generic propecia buy propecia finasteride drug class
    plavix blood donation propecia finasteride

  18. http://genericcialisworldwide.com/ generic cialis tadalafil runny nose generic cialis metformin onset cialis generic pills
    nitric oxide and cialis generic drugs

  19. http://genericviagrawp.com/ levitra mail order viagra buy cheap viagra viagra buy online uk sildenafil citrate
    buy viagra without prescription in japan

  20. http://genericviagrawp.com/ can i buy viagra over the counter generic viagra online buy viagra address
    buy viagra for women

  21. http://iaccutane.com/ serious side effects of accutane drug cheap accutane prescribe accutane drug
    roche to buy accutane

  22. http://iaccutane.com/ drug accutane birth control pills Isotretinoin astrazeneca canada accutane
    drug accutane birth control pills

  23. http://viagragenericsi.com/ interrogation buy viagra Sildenafil price buy viagra in europe eu
    only buy viagra prescription

  24. http://cheapcialisbestprice.com/ buy generic cialis 2005 buy cialis viagra femenina natural cialis generic
    generic cialis lowest price

  25. http://cialistadalafilpharmacy.com/ generic cialis online pharmacy generic cialis lowest price cialis generic viagra
    alcohol cialis generic

  26. http://cialisnet.com/ canada cialis generic viagra purchase cialis prozac no prescription cialis generic
    buy tadalafil pharmacy

  27. http://generictadalafilcialis.com/ low cost singulair cialis generic pills order generic cialis generic cialis ship to canada
    cialis generic promo

  28. comment4, doxycycline cost, [url=”http://doxycyclinerxph.com/”]doxycycline cost[/url], http://doxycyclinerxph.com/ doxycycline cost, gqw, buy propecia, [url=”http://propeciafpharmacy.com”]buy propecia[/url], http://propeciafpharmacy.com buy propecia, rnrl, Cialis, [url=”http://cialisrxpharmacy.com/”]Cialis[/url], http://cialisrxpharmacy.com/ Cialis, 8P, tadalafil, [url=”http://cheapcialispharmrx.com/”]tadalafil[/url], http://cheapcialispharmrx.com/ tadalafil, sbchj, Cialis Generic, [url=”http://genericcialisdrugstorerx.com/”]Cialis Generic[/url], http://genericcialisdrugstorerx.com/ Cialis Generic, 5680,

  29. comment1, http://prednisonerxph.com/ prednisone price, >:), http://cialisespanafarmacia.com/ comprar cialis precio, %P, http://zithromaxrxph.com/ buy zithromax, mauizr,

  30. comment1, http://canadianpharmacyfirst.com/ cheap drugs, 8-((, http://cialisfrancepharmacie.com/ cialis generique, mrezxp, http://zithromaxrxph.com/ zithromax fast shipping, >:]]],

  31. comment1, canada drugs, [url=”http://canadianpharmacyfirst.com/”]canada drugs[/url], http://canadianpharmacyfirst.com/ canada drugs, 8205, viagra en ligne, [url=”http://viagrafrancepharmacie.com/”]viagra en ligne[/url], http://viagrafrancepharmacie.com/ viagra en ligne, gxru, viagra generico, [url=”http://viagraespanafarmacia.com/”]viagra generico[/url], http://viagraespanafarmacia.com/ viagra generico, 5289,

  32. comment5, viagra en ligne, [url=”http://viagrafrancepharmacie.com/”]viagra en ligne[/url], http://viagrafrancepharmacie.com/ viagra en ligne, 516, generic drugs, [url=”http://canadianpharmacyfirst.com/”]generic drugs[/url], http://canadianpharmacyfirst.com/ generic drugs, ugta, Buy Cialis, [url=”http://www.cialisonlinepharmacies.com/”]Buy Cialis[/url], http://www.cialisonlinepharmacies.com/ Buy Cialis, 943,

  33. comment2, where can i watch free movies online, [url=”http://watchfreemoviesonlinereal.com”]where can i watch free movies online[/url], http://watchfreemoviesonlinereal.com where can i watch free movies online, =], Buy Propecia Here, [url=”http://propeciaaps.com/”]Buy Propecia Here[/url], http://propeciaaps.com/ Buy Propecia Here, trfdoa, doxycycline price, [url=”http://doxycyclinefst.com”]doxycycline price[/url], http://doxycyclinefst.com doxycycline price, 149427, download music for free, [url=”http://freemusicdownloadsreal.com/”]download music for free[/url], http://freemusicdownloadsreal.com/ download music for free, :-]],

  34. comment3, buy azithromycin online, [url=”http://zithromaxcom.com/”]buy azithromycin online[/url], http://zithromaxcom.com/ buy azithromycin online, =-OOO, buy finasteride, [url=”http://propeciacom.com/”]buy finasteride[/url], http://propeciacom.com/ buy finasteride, :-)), generic Cialis, [url=”http://cialisuscom.com/”]generic Cialis[/url], http://cialisuscom.com/ generic Cialis, 8-], buy zithromax, [url=”http://azithromycinz.com”]buy zithromax[/url], http://azithromycinz.com buy zithromax, 787,

  35. http://buycialispro.com/ online generic cialis Cialis buy cialis generic drugs
    used cheap generic cialis

  36. comment3, Cialis Generic, [url=”http://cialisgenericrew.com/”]Cialis Generic[/url], http://cialisgenericrew.com/ Cialis Generic, =DDD, Order Xanax, [url=”http://orderxanaxrew.com/”]Order Xanax[/url], http://orderxanaxrew.com/ Order Xanax, gvh, Cialis Price, [url=”http://cialispricerew.com/”]Cialis Price[/url], http://cialispricerew.com/ Cialis Price, nyede,

  37. comment6, buy tramadol online, [url=”http://cheaptramadolonlinefast.com/”]buy tramadol online[/url], http://cheaptramadolonlinefast.com/ buy tramadol online, dggvw, xanax generic, [url=”http://orderxanaxalprazolamfast.com/”]xanax generic[/url], http://orderxanaxalprazolamfast.com/ xanax generic, 8(,

  38. comment5, cialis, [url=”http://cialisgenericofarmaciait.com/”]cialis[/url], http://cialisgenericofarmaciait.com/ cialis, :-D, xanax pills, [url=”http://orderxanaxalprazolamfast.com/”]xanax pills[/url], http://orderxanaxalprazolamfast.com/ xanax pills, :-(((,

  39. comment2, Payday Loans, [url=”http://instantpaydayloansfst.com/”]Payday Loans[/url], http://instantpaydayloansfst.com/ Payday Loans, yfsg, bestpriceval.com, [url=”http://bestpriceval.com/”]bestpriceval.com[/url], http://bestpriceval.com/ bestpriceval.com, 9289, Generic Cialis Online, [url=”http://genericcialiscanadarx.com/”]Generic Cialis Online[/url], http://genericcialiscanadarx.com/ Generic Cialis Online, fjzt,

  40. comment5, Order Cialis, [url=”http://ordercialisonlinerx.com/”]Order Cialis[/url], http://ordercialisonlinerx.com/ Order Cialis, >:P, Cheap Viagra Online, [url=”http://cheapestviagraonlinerx.com/”]Cheap Viagra Online[/url], http://cheapestviagraonlinerx.com/ Cheap Viagra Online, 50115, Buy Cialis Online, [url=”http://buycialiscanadarx.com/”]Buy Cialis Online[/url], http://buycialiscanadarx.com/ Buy Cialis Online, =[[[,

  41. comment1, Xanax Price, [url=”http://www.bestpricex.com/”]Xanax Price[/url], http://www.bestpricex.com/ Xanax Price, >:)), Valium, [url=”http://bestpriceval.com/”]Valium[/url], http://bestpriceval.com/ Valium, xyza, Cash Loans, [url=”http://cashadvancepaydayloancapl.com/”]Cash Loans[/url], http://cashadvancepaydayloancapl.com/ Cash Loans, dcpg, Buy Cialis, [url=”http://buycialiscanadarx.com/”]Buy Cialis[/url], http://buycialiscanadarx.com/ Buy Cialis, hpquk,

  42. http://phmeds.com/ site edu cialis generic viagra without prescription herbal viagra for women cialis generic
    cheap generic cialis online

  43. http://phmeds.com/ tadalafil generic cialis viagra buy generic cialis in canada
    cialis generic india

  44. My wife and i have been really ecstatic when John could conclude his investigations out of the ideas he got through the blog. It’s not at all simplistic to simply find yourself giving for free methods that many most people may have been making money from. We really see we’ve got the blog owner to thank for this. The main illustrations you’ve made, the simple blog menu, the friendships you make it easier to instill – it’s most fabulous, and it is aiding our son in addition to us consider that this idea is entertaining, which is certainly very mandatory. Thanks for the whole thing!

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: