Sympathetic Ophthalmitis - A miraculous tragedy
Imagine losing your ability to see the world in all it's glory when you're 3 years of age - before you've seen the rainbows, the ocean, or a meadow full of orchids. Not something anyone would want to go through, right? Sadly, one little boy was unfortunate enough to endure this wicked twist of fate. But he didn't let that hamper him in any way. In fact, his name stands as a beacon of hope in the communication for the visually impaired throughout the world.
This is the story of Louis Braille.
In a small town near Paris, Louis Braille was helping his father at his harness workshop, when an awl (a sharp metal instrument used to drill holes in a leather harness) slipped from his hand and hit his eye. It was a freak accident that left him blind in both his eyes. Soon, learning by listening became increasingly difficult for him in a regular school. So when he got a scholarship to the Royal Institution for Blind Youth in Paris, he took it and there was nothing stopping him from then on.
When he was just 15 years old, he designed a code language which consisted of 6 dots embossed on a paper, arranged in various patterns each representing an alphabet. This wasn’t an entirely original invention. A 12 dot code language was designed by a former soldier named Charles Barbier to help soldiers communicate secret information on the battlefield without talking. But the 12 dot system was understandably more cumbersome and difficult to learn compared to a 6 dot system and soon ‘Braille’ came to symbolise the visually impaired around the world.
While this inspiring story motivates us to strive to invent something, most of us might have overlooked a subtle detail here. If you haven’t already thought about it, here is the question.
If the awl slipped his hand and hit one eye, then why did he lose vision in both his eyes?
To be able to answer this, it helps to refresh some concepts in immunology. In a previous article “The Unlikely Transplant”, we tried to explain why the fetus, despite being a foreign body in the uterus does not get rejected by the maternal immune system. We also learnt that the MHC Class 1 molecules kill intracellular foreign bodies by activating the Cytotoxic CD8 T lymphocytes and the MHC Class 2 molecules kill extracellular pathogens by activating the CD 4 T helper cells.
Now let us try to understand the immune system and mechanisms of autoimmunity in some more depth.
Spider-man’s most famous quote “With great power come great responsibilities” holds perfectly true for the immune system! During the development of the immune system, there are certain check points that make sure that the T cells and B cells are empowered to kill only the foreign cells like bacteria and viruses and not the body’s own cells. This ability of the immune system is called immune tolerance and the breakdown of this discipline within is thought to be the main reason of autoimmune diseases.
The checkpoints are two-fold; there’s a central tolerance check in the thymus for T cells and bone marrow for B cells. To make the system fool proof, there are peripheral tolerance mechanisms to check those cells that escape the central mechanisms. During development the immature T cells and B cells are screened by the thymus and bone marrow respectively and those cells that are found to recognise self antigens are eliminated by apoptosis (programmed cell death).
Only those cells which can “tolerate” the body’s self antigens are allowed to enter the circulation thus minimising the possibility of autoimmune cell destruction.
However, there are certain cells in the body which are never pitched against the immune system in this litmus test. These sites are called immune privileged sites and some of the well established examples include the spermatozoa, cells of eye lens and uveal pigment cells. These cells are never exposed to the immune system. If they accidently enter the circulation at some point in the adult life, the immune system owing to its natural instinct to fend off anything foreign, now mounts an immune response.
When the awl hit his eye, some of the lens proteins were released in the circulation. That set off the alarms in his immune system – antibodies were formed against the lens proteins and released into the circulation which eventually destroyed both the eyes by delayed hypersensitivity reaction. This phenomenon is called Sympathetic Ophthalmia. The pathological features in both the eyes look identical, as though the healthy eye is sympathising with the injured eye. The patient presents with angry looking red eyes, lacrimation, tenderness and a generalised inflammation of all the layers of the eye which gradually progresses to loss of vision.
The advent of topical and systemic corticosteroids has reduced the incidence of sympathetic ophthalmia. Any penetrating injury of the eye should be treated with corticosteroids to quieten the injured eye. A crucial and timely decision to enucleate the injured eye in a last ditch attempt to save the healthy eye might have to be taken. But if the antigens are already released into the circulation, then it is only a matter of time before the immune system wrecks havoc. The worst part about it is there’s absolutely no way to know if these antigens have entered the circulation, before visible clinical features appear in the sympathising eye. And that’s a catch-22 situation!
Author: Soundarya V (Facebook)
Sources and citations
Braille, Louis. American Academy of Ophthalmology, 10 Oct. 2017, www.aao.org/biographies-detail/louis-braille.
Ramanjit Shiota, and Radhika Tandon. Section IV - Chapter 24 : Injuries to the Eye . Parson's Diseases of the Eye, 21st ed., Elsevier, pp. 387?388.