Part 1
Age Related Macular Degeneration :
From antiquity to modernity
Tracing the journey of treatment for this blinding condition
( ref : Wikimedia commons)
by Dr Chinmay Nakhwa
The evolution of eye treatments has had an interesting history. It was in the late 19th century when Howe first photographed the human retina and documented it ( This has had many controversial claims). Since then diagnosing diseases of the retina and treating them has been quite an enigma among eye doctors.
Age related eye problems of the retina ( AMD: Age related macular degeneration ) were first classified by Sir Stewart Duke-Elder as “ Senile degeneration of the retina”. In this condition , fine blood vessels grew under the central retina. Being fragile, these vessels ruptured easily, causing a sudden and irreversible drop in the patient's vision. This was responsible for up to 20% cases of blindness in people beyond 65 years of age, in those days.
Many treatments including steroid injections around the eye etc were tried but they were mostly ineffective.
For close to a century since AMD could be diagnosed and photographed, there was no treatment available to halt this blinding condition.
Macular Photocoagulation
( ref :https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1442-9071.1989.tb00566.x)
The discovery that thermal lasers could be used to treat diseases of the retina by Gerhard Meyer-Schwikerath, 1946, opened up many possibilities for the treatment of macular degeneration. Laser was found to be effective in reducing the risk of blindness in diabetic retinopathy. A similar logic was applied to the treatment of AMD.
The thesis was that if the leaking blood vessels were destroyed with laser, then it would prevent the vessels from rupturing and bleeding. This bleeding usually caused debilitating scars in the patients retina and hence caused blindness. The laser was supposed to prevent this.
To summarize, the laser treatment DID succeed in halting the progression of macular degeneration, but unfortunately produced a large scar on the patients retina ( due to the laser) which eventually cost the patient his vision!
I've had a couple of casual discussions with my teachers from Sankara Nethralaya about this treatment. What was the counseling conversation like those days? Well, the doctors simply told the patients-
You have a blinding condition in your retina. We can treat it with a laser, but you might lose some vision due to it. If we don't treat it, chances are that you might lose all of your vision!
From where we are today, this conversation seems almost unbelievable!
The Era of photodynamic therapy
The limitations from thermal lasers took researchers back to the drawing board. Could they develop a laser which did not burn off the patient's retina? Could they develop a “ cold laser” which would arrest blindness due to macular degeneration?
This led to the development of Photodynamic therapy( PDT). So was PDT a radically new technology ?
Well it seems it has been active in the Indian milieu since antiquity!
In one of India’s sacred books, Atharava-Veda (1400 BC), patients suffering from vitiligo were given certain plant extracts of the Bavachee plant, Psoralea corylifolia, and were asked to stand in sunlight for some time. Ancient civilisations - Greeks, Chinese, Romans used sunlight to cure a wide variety of ailments like vitiligo, skin cancers, rickets etc.
In modern medicine, the discovery of hemato-porphyrins rekindled the potential of this form of treatment. At the turn of the 21st century PDT was being used to treat skin conditions like vitiligo and some forms of skin cancer. This was also used to treat solid tumors and some form of blood cancers
So the possiblity of using this treatment for macular degeneration was exciting !
What if we could photosensitize the leaky blood vessels of the retina with a porphyrin based dye and then activate that dye using special laser? Well that would shrink those blood vessels and not burn off the retina like a thermal laser! Voila!
However the process of doing a single sitting of PDT was quite a process.
The patient had to be checked for any allergies to the porphyrin dye. Then after measuring the “ Body surface area” the dye had to be given intravenously in a specific concentration, very very slowly. Following this a special red laser was applied to the patients retina for a minute and a half.
That wasn't all. Following the laser, the patient had to wear full sleeve shirts, gloves, hat and dark glasses and avoid any bright lights for 48 hours (Since he was injected with a photosensitive dye, bright lights carried the risk of skin burns!). This meant that the patient had to stay indoors for two whole days! Typically patients scheduled their PDTs on Friday evenings so that they could have their down-time over the weekend.
So did this treatment deliver what it promised? To an extent- it did. It did shrink the leaking blood vessels in the retina. It thus stabilised the vision, but did not improve the vision significantly.
Was it permanent? No, It wasnt. Many patients needed repeated sessions periodically.
Was it cheap? No it wasn't. The pharma company, being the only one manufacturing the dye, had an obvious monopoly. And the dye came at a good cost to the patient.
The procedure shrank the leaking retinal blood vessels, but also to a certain extent affected the normal retinal tissue and caused collateral damage. So eventually the patient did end up with a significant “ Blind spot” in the central retina.
These outcomes along with the cost of treatment and the down time that went with it, did leave the doors open for development of a new product which had a better acceptance among patients. Thus began the era of Intravitreal Pharmacotherapy - injections given inside the eye to control the leaking blood vessels.
More about Intravitreal pharmacotherapy in Part 2.
Very interesting
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