BRIMONIDINE AND NEUROPROTECTION

• The main risk factor identified so far for the development and progression of glaucomatous optic nerve degeneration (GOND) is elevated intra-ocular pressure (IOP).

• It is also known that non-pressure dependent mechanisms may play a significant role in the etiopathogenesis of glaucoma. This is seen in normal tension glaucoma (NTG) and those individuals in whom IOP is presumably controlled to statistically acceptable levels.

• Management strategies for glaucoma are focusing on neuro-modulation, neuro-protection and neuro-regeneration.

• Brimonidine tartarate 0.15% (BT) reduces IOP by decreasing aqueous production (inflow) as well as by increasing uveo-scleral aqueous outflow. This molecule is also being investigated for its role in neuroprotection.

• BT is a third-generation alpha-2 adrenergic agonist. It has >1000-fold selectivity for alpha-2 receptors (compared to alpha-1 receptors).

•  BT acts initially by reducing aqueous production and on chronic use increases uveo-scleral outflow.

• Neuroprotection refers to the ability to preserve anatomic and functional integrity of the retinal ganglion cells (RGC), without the role of lowered IOP, thus preserving the visual field.

• The retina contains alpha-2 receptors primarily in the ganglion cell layer and inner nuclear layer.

• BT requires an in vivo concentration of 2 Nm to activate alpha-2 receptors significantly.

• In a study, the drug was instilled prior to vitrectomy and vitreous samples collected intra-operatively. The mean BT concentration was 185 Nm, high enough to reach the retina. Therefore, topical BT is presumed to be effective in the retina adequately.

• The Low-Pressure Glaucoma Treatment Study (LoGTS) reported progression of visual fields was reduced by 9.1% in eyes treated with timolol and by 39.1% in eyes treated with BT, after 2 years of follow-up.

• In a chronic ocular hypertension rat model, subcutaneous injection of BT and timolol were studied. BT treated eyes had 50% less RGC degeneration compared to timolol treated eyes. Similar results were obtained on intra-peritoneal injection of BT in rat models of glaucoma. Ischemia induced and crush injury models also showed enhanced RGC survival and preserved ERG b wave following administration of BT.

• Patients undergoing laser treatment for choroidal neovascularization were treated with BT 4-48 hours prior to the procedure and continued treatment for one-month post-laser. BT treated eyes had better visual acuity preservation. This was attributed to the protective effect of BT on the neuroretina from laser-induced collateral damage.

• In a study of ocular hypertension patients, BT and timolol were compared for their effects on retinal nerve fiber layer (RNFL) thickness. Scanning laser polarimetry (GDx) showed less progression of RNFL thinning in eyes treated with BT over a 12-month follow-up.

• Another study compared BT with 360-degree argon laser trabeculoplasty (ALT).  Although IOP reduction was comparatively less in BT treated eyes, visual field progression was slower.

• BT treated eyes have also shown improved contrast sensitivity.

• BT is presumed to act through alpha-receptor stimulation which inhibits the signals triggering apoptotic cascade in the RGCs.

 

• The mechanism of proposed brimonidine neuroprotection is unclear. In one study of ischemic injury to the retina in a rat model, brimonidine was shown to lower glutamate concentrations in the vitreous humor. Based on these results, it has been suggested that brimonidine might be neuroprotective because it prevents glutamate-associated excitotoxicity. Alternatively, it has been suggested that brimonidine may directly inhibit apoptotic pathways.

• Further studies are required to confirm the suitability of BT as a neuro-protective agent.

FURTHER READING:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709013/ 

PROTECT THE NERVE

DIET, FOOD, DRINKS AND LIFE-STYLE IN GLAUCOMA

Glaucoma is treated by drugs, through lasers or by surgery. However, research has shown that diet may have a positive or negative effect on the outcome of this potentially blinding condition.

Initially, elevated intra-ocular pressure (More than 21 mmHg) [IOP] was regarded as the main cause for glaucomatous optic nerve degeneration (GOND). However, later other mechanisms were presented in the etiopathogenesis of this disease. These include the vascular theory (which is based on altered ocular blood flow and other mechanisms), biochemical theory (which blames a number of biochemical mediators) and some other theories such as genetic, glymphatic and translaminar pressure difference (pressure between the eyeball and brain).

During metabolism there is continuous release of oxygen free radicals (OFRs) by the tissues in the body. These OFRs are responsible for damage to structures including retinal ganglion cells (RGCs), leading to progressive loss of vision. However, certain mechanisms are usually present in the body to take care of these excessive OFRs. These mechanisms include: anti-oxidant enzymes (such as= superoxide dismutase, catalase, glutathione peroxidase) and free radical scavengers (For e.g. = glutathione, alpha-tocopherol, betacarotene). A number of anti-oxidants also occur naturally in certain foods.

Intake of foods rich in anti-oxidants such as carotenoids may have a positive impact in slowing the rate of GOND. Certain foods which have been found to contain large amounts of carotenoids includes fruits and vegetables with red, yellow and orange hues. Thus, carrots, squash, grapefruits, oranges, apricots, cabbage, peaches, green beans, spinach, kale and beets have an important role in providing carotenoids. It has been found that consuming eggplants (10 gm/day) may reduce intra-ocular pressure (IOP) by 25%. Similarly, ≥2 servings per week of oranges and peaches are useful.

Eggplant

Vitamins with antioxidant property are Vitamin A, C and E. They are present in carrots, radishes, Brussels sprouts and celery. Some other anti-oxidant rich foods are: pomegranate, acai berries, cranberries and dark chocolate.  Vitamin E is available in eggs, wheat germ and nuts. 

Minerals such as zinc, manganese, magnesium and selenium also have anti-oxidant properties. Foods which contain these trace elements include: red meat, poultry and seafood (especially oysters). 

Blackcurrants contain anthocyanins which are neuroprotective and also normalize ocular blood flow. 

Docosahexaenoic fatty acids (DFA) and total omega-3 long-chain polyunsaturated fatty acid are useful in improving ocular blood flow, impaired systemic microcirculation and neuroprotection. Some of the excellent sources of these fatty acids are wild-caught salmon, tuna, herrings, sardines and mackerel. 

Salmon

Flavonoids are polyphenol compounds present in plants. They have antioxidant properties and are neuroprotective. Some good sources of flavonoids are: cocoa, green tea and red wine.

Green tea

Regular exercise is useful for glaucoma by improving blood flow. However, some of the postures in yoga should be avoided as they increase IOP. A slightly raised pillow (20⁰) is also advisable.

On the other hand, certain foods are damaging to the eye and worsen GOND. These are diets containing high levels of trans fatty acids such as baked goods such as cookies, cakes, donuts and also fried items such as French fries or stick margarine. Salt and caffeine should also be avoided as they may increase blood pressure (BP). Smoking also reduces ocular blood flow and may worsen the GOND.

Although evidence is mixed regarding the role of diet in glaucoma, yet a healthy lifestyle including proper nutrition, exercise and avoidance of harmful activities such as smoking or excessive alcohol consumption may have an overall positive impact on the body. As  Felix Lagrange (1922) said: “Glaucomatous optic nerve degeneration is a sick eye in a sick body”.

                 

Glaucomatous optic nerve degeneration