AMD, untangled or tangled - The Parkinson's "dot" on my retinas

Ohe "retina" is commonly referred to as an organ that acts as a "mirror" for vision, transmitting images to the brain, which processes them and transmits them to us. 

The retina (1) which is made up of nerve-type tissue, neurons, consists of a part further from the centre, the peripheral retina, and a central part, the macula with a tiny surface called the fovea in its own centre. (2). Between the peripheral retina and the macula-fovea... (3)The histological composition differs in particular in the concentration and distribution of cone and rod cells.

If an organ is defined by its form and function, then it can be argued that, despite its small size, the retina within the eye is to be considered both as a physical component of the ocular-optic apparatus and as a set of two elements, which could be called the "retinal system", in the same way that we would speak of the oesophagus and the stomach in the digestive system.

 

Retinal system precisely formed of two organs which, although having similar components, are distinguished by their composition and function: one to see the world as a whole, the other to read, even the finest.

Taking this distinction radically into account, between the two parties, as we will have understood, is appropriate, even necessary, to open up fruitful lines of work on AMD, which is mainly "reading blindness".

In any case, it is a question of not accepting as inevitable the degeneration as a whole, which is the cause of visual impairment, nor the loss of the fovea and its fundamental and distinctive function of the human species, reading.

 

There is no doubt today that the changes in methods brought about by the AIDS health crisis have led to the following changes (4), and the call for multidisciplinarity in the broadest sense, patients/doctors/researchers/laboratories, is an example of successful joint work that has usefully advanced research.

 

With regard to AMD (for which estimates of the number of people affected in France in the short/medium term concern more than 2 million people), it is important to note that the number of people affected in France in the short to medium term is estimated at more than 2 million. (5)), compartmentalisation or what is still far too little cooperation between medical and scientific disciplines - in particular ophthalmology and neurology - seems to be a serious handicap to progress in these fields. 

 

As far as I'm concerned, for some time now, I've always needed more light. I also knew I had "druses". (6), but anyone can have them.

One morning, one of my retinas seemed to self-destruct: the lines of my computer began to ripple and I saw a hole in front of me.

It was a "declaration" of macular degeneration, not so much age-related (early 60s). I lost my eyesight fairly quickly, in stages. So it would appear that the disease starts in the fovea and then spreads. At least that's my experience.

 

Over the years, I have consulted several ophthalmologists on lists of "AMD specialists. One after another told me that in my case there was nothing I could do. Except once, an injection of an overpriced product, the Lucentis, used in a completely different pathology, and which is used here to sclerotize the retinal capillary vessels in the eye, which not only multiplied but burst. Hence the name for the "wet" form of AMD, known as exudative, while in the "dry" form, known as atrophic, the capillaries have not burst, or have not yet burst. When these vessels burst, it produces a micro-hemorrhage that obstructs the "mirror" function of the retina like a stain. So once this happens, it stops the effect of wet AMD. A dry form can remain dry. The product does not "cure" the disease: it does not act on the principle that causes the pathology, which, when it remains dry, also impairs vision through the main cause of the disease, which is the deterioration of the cells themselves.

 

This injection therefore stopped a degradation of the tissue at its precise location, but did not restore the function of the retinal organ: the loss of vision linked to the lesion effect of this degeneration persists, and recurrence at another location is possible. Some patients are known to receive several injections depending on retinal events, or even for prevention. Partial material effect on tissue, but not always on function. We prick when capillaries multiply, randomly, and burst or threaten to burst, so we have to make and redo these OCTs - expensive tests - hoping to pass in front of the device one day when it is not too late to prick. This too has not been precisely explained, and I am not sure that this random aspect is explained to patients. So one of these specialists brought me back several times a year. He (7) saw "so many people" that he stood there with his nose in front of his plane, so much so that one day he called me by the name of the next patient. I've often wondered how these practitioners (8) could call themselves "specialists".

 

One day, a new ophthalmologist, less pretentious and more serious, told me: "your condition has a name: legal blindness", and he wrote it down. It was he who taught me, not his colleagues, that when visual acuity is one tenth or less, the law declares us to be "legally blind".

It was a "disaster" in the logical sense, as well as a relief: a change in social identity as well as in my inner self, and recognition of my situation by a Disability Card.

 

Contrary to what happens in glaucoma, it is the central vision that deteriorates in macular degeneration. Now, I come back to it, the central vision is the only one that allows to read, that is to say to see "the thinnest". In the animal kingdom as a whole, reading is a specifically human activity. What we do not think about, when we are not deprived of it.

 

Peripheral vision in AMD is less affected. However, it probably doesn't benefit from the combined precision of central vision, so it seems to be diminished nonetheless.

 

As for my visual deficit: if I can distinguish the shapes of buildings, of what moves, if I can differentiate a large vehicle from a small one, I cannot distinguish a bus from a coach, and I cannot read the number of its line. In the same way that I cannot always distinguish a man from a woman, or a breed of dog. I can't recognize the people speaking at a conference, or in some meetings. I can't recognize a friend on the street... But they say, "ha, she's got autonomy...". It's true, but often I'm wrong... and I fall on the sidewalk, or I open the door of a car that's not the one waiting for me... I can pick up shapes, but not the detail... sometimes a letter, but not the word. Not the Metro line if I have to change it. This is precisely what makes me say that the macula-fovea functions as if it were not the same organ, because it is only it, I insist, that reads the letters and locates the end, like a text - or the features of a person.

 

The visual acuity score method is a good indication that ophthalmology considers the retina as a homogeneous functional unit. Thus, according to the measurement method in force in France, we cannot officially dissociate the two acuity levels: for example, we can say that we have, which is my case, 0.5 tenths of vision in central vision and what I estimate to be about 2.5 tenths in peripheral vision. This is not in the standards or practices, and even the AMD specialists who know this well, have not invested in it. We have to submit to an examination that is codified in measurement methods that cannot properly account for our vision function and precisely for the particularity of the pathology, this difference in state between central and peripheral retina. The patient is aware of this dissociation of acuity and is disturbed by it. Some, for example, can read with great difficulty but can still drive carefully if their peripheral retina is not too badly affected. They know that we are not talking about near and far vision, but about the centre and the periphery. It is a paradox that the measuring tool that "regulates" the state of "legal blindness" is based on reading ability, whereas research, as we shall see later, does not always put this function in the foreground.

 

It is clearly insufficient to say, as a supposed consolation to an affected patient: "Don't worry, you will never go blind". And besides, legal blindness starts at 1/10th. We are faced with political, medical and sociological contradictions. We are also faced with a health observation as vague as "AMD vision": for the public authorities, without further reflection, the aim would be for the population to be satisfied with average performance, capable of maintaining a real or a semblance of median perceptive performance. This objective certainly serves the idea of an average in a population. With the representation that these "averages" confer a certain level of autonomy on the overall population. And so, it exonerates the public authorities from inciting to dig deeper and, among other things, to avoid integrating certain pathologies into "national causes".

 

Yet how can this still be considered as harmless for the foundations of the scientific study of pathology, at the epistemic level, since the study itself has not offered many recent advances?

 

The history of medicine shows how many discoveries were made when research changed its approach. And it is by posing itself as close as possible to observation and phenomena that Science has made leaps and bounds.

 

Will the current medical approach be perpetuated until a practitioner is himself afflicted with the pathology? No one would wish this on anyone. In fact, when so many researchers are working in labs without "finding" anything, what real risk would there be from another hypothesis?

 

The essential relationships between the brain and retinal cells as differentiated neurons are critical in the various modalities of vision. With AMD, we are indeed in a neurological pathology, even if, as we've seen, it only affects a tiny area. So I propose that we look at it as one of the major degenerative neurological diseases that we know of. Basically, let's not be afraid of words, retinal Parkinson's disease (9).

 

My epistemological work on the evaluation of medical data supports my personal experience as a patient suffering from a pathology that still remains a grey area despite the intensity of specialist research.

 

As we have seen, throughout the retina, the distribution of rods and cones is uneven. There are many more cones in the fovea, and more rods in the peripheral retina. More light sensitivity on the periphery, but much less precision.

 

I therefore propose to take into account a new approach, based on this reflection: starting from the fact that the central retina and the peripheral retina present a difference, then take as a basis for work, that of considering the retina as a system comprising two linked yet distinct organs.

 

The idea is to study AMD and its possible treatment by focusing more on the central retina and its "fine mind-reading" function.

I insist on it, for a tiny surface that can be counted in a few square millimetres, the fovea and its high concentration of cones, which is a histological difference, is well responsible for the fact that, if I can see a shape (with my peripheral retina), I cannot read, nor distinguish the features of a face.

 

Having studied the pathology, within the limits of my own observation and the measure of my possibilities, I have found that there is a "treatment" and not a healing therapy for certain forms and cases, but we have not yet found "the" treatment modality or "the" surgery that would "heal", as for other syndromes. It is therefore legitimate to ask whether the right methodological angle has been taken.

 

At first glance, we could say that three approaches oriented towards "global vision comfort for minimum autonomy" mainly emerge from the work: slowing down degeneration, transplanting natural cells, fitting a prosthesis. 

Thus, in France as well as in California and Japan, researchers are looking for ways to replace the affected central retina with an artificial retina or tissue graft.

 

On the tissue grafting side, an "acceleration" has occurred in the continuation of the work of the 2012 Nobel Prize awarded to two scientists (10) who found a way to dedifferentiate cells. But for this eventual gene therapy protocol, we must first find a safe way to prevent the stem cells from proliferating so that the surface area remains equal to itself. This is a way, as yet uncontrolled, of differentiating totipotent stem cells and effectively incorporating them into an organ. This "seductive" route is a hope, but for the time being, the risk is obvious.

 

On the prosthetic side - and we can salute here the work of Professor Sahel and his team - the very first implants (11)(five) have recently taken place, and offer some hope, although use requires complex external equipment for the transmission of "information" from the prosthesis to the optic nerve. In addition to the fact that this device will have to wait for the progress of miniaturization, the long-term tolerance of the graft on the central retina, and its impact on the evolution of peripheral vision, remains to be discovered. 

 

The limit, one might say, is missing, namely a true restoration of reading, so research should focus on compensating or repairing the fovea. Not to accept the degeneration/loss of the fovea...the heart of the disease seems a priori not to have been sufficiently worked on yet.

On the indications of my orthoptist (12), I discovered the existence of research directed by Alain Prochiantz, who has devoted himself to the study of cerebral morphogenesis. (13). Notably, with an experiment showing an improvement in mouse amblyopia. Of course, amblyopia is not AMD, but we are indeed there in the neurological register, and analogically, wouldn't the "principle" of this experiment be a way to go further anyway?

 

Of course, I am not perfectly informed about the details of the programmes but, in the spirit of the recognition of patients' knowledge about their pathology, (cf. Public Health Law(s) "for the taking into account of patients' expertise"), from my experience and observation (14), I call for the intensification of transdisciplinary cooperation between ophthalmologists and researchers in neurotransmission and plasticity, as seems to me to be the spirit and even the ethics of the Collège de France. (15).

 

Let me emphasize that AMD is, within the ocular system, a pathology of tissues within the nervous system. What is disturbing is that this degeneration occurs in a very small area of the nervous tissue. This makes it difficult to relate it to diseases that affect, for example, the volume of the brain or spinal cord. The cells of the retina are neurons, differentiated, but neurons, and in this respect, it is appropriate to consider the retina as a part of our nervous system.

 

I found nearly one hundred and fifty theses with the keyword "dmla" in them. (16), supported between 2009 and 2019. About fifty of these theses seem to be centred, even partially, on the fovea, and half a dozen, among the most recent, are oriented towards the fight against degeneration. And I noted that twenty-six theses respond to the key words "dmla" and "Parkinson" ... And all these theses are spread over twenty or so "university fields" ... This shows how fragmented the research is, and the culture of transversality is really struggling to emerge.

 

Among these works, in 2011, in his thesis (17) presented in Sciences of psychophysical approach, Aurélie Calabrèse writes however in Chapter 3 - Reading and functional adaptation to the presence of a scotoma: "... the presence of a scotoma is a very important factor in the development of the brain. Even with increasing font size, the average value of the maximum reading speed decreases from the fovea to the periphery. Legge et al (1992) showed that among 141 patients entering a low vision clinic, only 30 % reached normal reading speed thresholds for very large type sizes. Letter size magnification is therefore not sufficient to recover a standard reading speed. These results allow us to reject the scaling theory and to conclude that font size is not the only factor limiting reading performance in off-centre vision. ".

 

This work confirms what I am experiencing, the enlargement of a text to make it read by the peripheral retina, does not solve the problem of reading.

 

As we have already seen, we should therefore be able to "compensate" or "repair" the macula-fovea.

 

It is moreover, it seems to me, from this angle that in March 2018, Hugo Charles-Messance, presented his thesis in Physiology, Physiopathology and Therapeutics: "Role of interleukin -1 beta (18) in photoreceptor degeneration associated with age-related macular degeneration". Charles-Messance reminds us that " one of the late forms of AMD - is characterized by the loss of pigmentary epithelium and photoreceptor degeneration", also that "in geographic atrophy, mononuclear phagocytes (PMs) accumulate in the subretinal space, and induce retinal degeneration", and that "in the late forms of AMD, the pigmentary epithelium is lost and photoreceptor degeneration occurs". "and it demonstrates that" the presence of subretinal PMs is associated with loss of rods and degeneration of cone segments in the transition zone of atrophic patients ». Then, after finding and describing a process of neutralizing the causes of cone segment degeneration and rod loss in subretinal inflammation, he concludes: " This study will allow the development of innovative therapies to fight the atrophic form of AMD, for which there is currently no treatment. " (19).

This is also the sense of the search for these small protein factors that can inhibit the atrophy and destruction of certain segments of the cones of the fovea.

 

I have no doubt that ophthalmology professors are attentive to the work of neurologists, but we hear little or no mention, as in theses, of groups of researchers working together.

By "multidisciplinarity" (or transdisciplinarity), I do not mean welcoming other disciplines into a Centre already dedicated to a medical speciality, but rather a framework structuring true plural cooperation.

 

While it is commonplace to recall that research in France is divided into disciplines, this observation turns into despair for patients suffering from pathologies that fall within the scope of several of them.

So it's all about approaching AMD as a neurological disease. And to consider the retina as a two-organ system, with the goal of restoring the "reading-thin vision" function of the macula-fovea of affected patients.

 

Furthermore, as an AMD patient, I also hope that the patient/medical body partnership will, as we have seen with other diseases, achieve its full potential.

It can be estimated that more than four million people over the age of fifty will be affected in twenty years' time. So why not declare AMD "endemic"?

 

I appeal to consider as a great national cause, that of "Restoring reading in everyday life", that is to say, recovering reading as "a good specific to humanity".

 

Paule Perez, Psychoanalyst     

 

Header image : Illustration ©Giacomo Bagnara