WORLD GLAUCOMA WEEK
11TH MARCH TO 17TH MARCH


GENE DIRECTED THERAPY: A HOPE FOR GLAUCOMA PATIENTS

Glaucoma, a hereditary disease, is the second major cause of blindness in the world. Almost 4 % of the population after the age of 40 suffers from glaucoma and the greatest tragedy is 30 to 40 percent of them are not aware and gradually become irreparably blind. Some people even after diagnosis do not follow doctor’s advice and become blind.

Every eye has certain intraocular pressure which is essential to maintain health and function of the eye. A fluid called Aqueous humor is constantly formed by the Ciliary body. This fluid provides nutrition to the lens and cornea and is gradually drained out of the eye along with waste products through the Trabecular Meshwork ( T. M) located at the Angle of Anterior Chamber.. Normally a balance is maintained so that the Intraocular Pressure remains within normal range, i.e. 15 to 19 mm of mercury. In most of the glaucoma patients, due to some hereditarily acquired Gene defect, trabecular meshwork creates resistance, thereby the IOP gradually increases and it causes Ganglion Cell death, which are vital for visual function. This leads to damage to Optic Nerve head and the Field of Vision gradually get constricted. If this process is allowed to continue, the eye becomes totally and irreparably blind...
Most of the time such glaucoma, which is called, Chronic Simple Glaucoma has no alarming symptoms and hence the patient does not consult an Ophthalmic surgeon or Glaucoma specialist. The only symptoms may be little heavy ness of eyes or slight ocular pain or fatigue or little watering from the eyes. The vision may remain normal, i.e., 6/6 even in some advanced cases of glaucoma.
.That is the reason that 30 to 40 percent of patients gradually progress towards blindness without being aware of the disease. Some patients may develop early or disproportionate presbyopia or dusk blindness and in advanced stage, night blindness. The disease is relatively more common in Myopes and diabetic patients.
There is another type of Glaucoma, called Acute Glaucoma, which gives lot of pain in the eyes and the eyes become blind rapidly. It needs prompt medical, laser or surgical treatment. These patients mostly have hypermetropic refractive error.

How Glaucoma is diagnosed?

Ophthalmologist when suspects the patient to have glaucoma, records the pressure of the eye by Tonometry and examines the fundus by Ophthalmoscopy to evaluate the effect of IOP on the Optic Disc. Finally, he records the fields of vision by Automated Perimetry and visualizes the Angle of Anterior Chamber by Gonioscopy and reach to final diagnosis.



Medical Therapy.

In modern time there are various types of drugs which can normalize the IOP to a level of 14-16 mm of mercury. It is extremely important that the patient follows doctor’s instructions as regards time and frequency of instillation of one or multiple drugs and the patient has to visit the doctor regularly for recording of IOP and if necessary, Field of Vision. For some of the patients, an ideal IOP would not be 16 or 17 but 12 or 13 mm of Hg and such an IOP is called Target IOP for that particular patient.

Laser Therapy

Laser procedure to create a hole in the iris is an extremely useful procedure in Acute Glaucoma. In Chronic Simple Glaucoma, in Indian eyes, laser surgery is not much rewarding. It is only reserved for patients who are unfit for elective surgery

Surgery.

When inspite of maximum tolerated medical therapy, we are unable to achieve ideal Target IOP, a surgery is advised. The surgical procedure, most commonly and successfully done is called Trabeculectomy. In expert hands, it practically has no risk and can be successful in 95 percent of eyes to control the pressure with out the help of glaucoma drugs. The success of the surgery may even be life long.

New Evolving Therapy of Glaucoma: Gene Therapy and Stem Cell Therapy.

Gene Therapy.

Glaucoma occurs mostly due to two reasons: either excess of formation of Aqueous Humor or normal formation of Aqueous but gradual obstruction of the drainage of the Aqueous due to some Gene defect in the Trabecular Meshwork located at the Angle of Anterior chamber.
Certain Genes, namely, Myocillin, Optineurin and WDR36 have been identified as the causative factor of glaucoma. Scientists have developed some Genes which can be injected in the eyes to modify or block the function of glaucoma causing genes.
Therapeutic genes are attached to some viruses/adenoviruses which act as vector to be injected in the eyes. Researchers have noted significant reduction of IOP after such injections in laboratory animals.
Secondly, the raised IOP cause death of Ganglion cells which are extremely essential for visual function. Scientists have found a Gene, namely, Trk B, which can be injected with the help of adenovirus as vector in the vitreous. These injected Genes were to a great extent successful to prevent death of Ganglion cells and hence prevention of blindness. The injection of Neuroprotective Brain Derieved Neurotrophic factors (BDHF) in the vitreous too has given very encouraging results.
Researchers are trying to use the therapy to permanently incapacitate the glaucoma causing genes and to safe guard or prevent the death of Ganglion Cells.




Stem cell Therapy.

The blindness in Glaucoma occurs due to death of Ganglion cells which results in changes in the Optic Disc. (Cupping of the disc). Scientists have taken stem cells from the bone marrow which were so processed to produce Neurotrophins which are essential for survival or activation of ganglion cells. Scientists were successful to reactivate some of the Ganglion cells, there by giving some vision to practically blind rats...


We are hopeful that in coming decade or two we shall be able to identify all glaucoma prone patients by Gene evaluation much in time and shall be able to modify or block the function of such genes. National Eye Institute USA is sponsoring Phase 1 clinical trial and studies are also taking place in U.K. Stem cell therapy gives some hope to patients who are already in advanced stage of blindness due to glaucoma.


Prof M. R. Jain
Glaucoma Expert & Editor, Text Book Of Glaucoma
Medical Director
Jain Eye Clinic & Hospital
Jaipur