Syed Hasnain was born in Pakistan and graduated from Nishtar Medical College in 1963. After graduation, he completed his ophthalmology residency. He served as a demonstrator in Physiology for a few years before moving to United Kingdom and obtained a diploma in Ophthalmology from the Royal College of Surgeons, England in 1969. After working in ophthalmology departments in various hospitals in England he migrated to the United States in 1974. Dr. Hasnain received board certification from the American Board of Ophthalmology in 1977. He is currently in private practice, which he began in 1980 in Porterville, CA.
Summary of glaucoma research:
In 1970 during a routine eye exam, I was found to have an elevated intraocular pressure of around 30 in each eye. I could not tolerate any glaucoma eye drops and didn't opt for surgery for fear of complications, so I never got treated for my high IOP. My CCT readings are in normal range at 545 each eye. Forty years later, I still have high IOP of 30, yet no loss of vision or visual fields. It was very puzzling: why didn't I become blind even after 40 years of high IOP of 30 whereas my patients were becoming blind even at a normal range of IOP of 15. I found glaucoma in the terms of cupping very confusing. Ironically, we are using the same cupping parameter to differentiate between physiological as well as pathological cupping, no wonder it is creating confusion in glaucoma. Not finding satisfactory answers to my puzzling questions in textbooks or literature, I resorted to my own glaucoma research.
Is cupping really occurring in glaucoma? The term cupping implies that physiological cup starts enlarging and the nerve fibers are being atrophied in response to raised IOP in glaucoma. The physiological cups of various sizes are formed due to varying degree of atrophy of the Bergmeister Papilla, a tuft of hyaloid vessels originating from the disc and supplying nutrition to the lens in fetal life (Wolf's Anatomy). If this is true: then why should a remnant fibrous tissue plate enlarge concentrically in response to high IOP? It is also extensively published that nerve fibers are present in the rim area only whereas the central cupped area is empty and devoid of nerve fibers. But I was unable to find a single histology of normal or diseased disc, having such a doughnut shaped arrangement of nerve fibers. Histology of all the normal optic discs reveal that the entire disc is densely packed with nerve fibers and there is no central empty space. Then why are we talking in the terms of cupping of disc? The fibrous tissue plate forming the floor of the physiological cup is identified as a central connective tissue meniscus lying superficially on the surface of the nerve fibers layer (Wolf's Anatomy). If true: then why have we been giving so much importance to the fibrous cups which are not even part of neuronal tissue of the disc?
Another puzzling question about cupping is based on the arrangement of nerve fibers in the retina/optic disc and the way glaucomatous visual fields are produced. The nerve fibers originating closest to the disc lie most superficial (closest to the vitreous) and exit from the central most part of the disc, whereas the nerve fibers originating from the most peripheral retina lie deepest (closest to the sclera) and exit closest to the scleral edge. If cupping was indeed taking place then the nerve fibers originating closest to the disc should had been destroyed first because of their central most location in the disc, resulting in concentric enlargement of the blind spot. On the contrary, the peripheral vision fibers are always, invariably, destroyed first in glaucoma. Keeping in mind the remnant fibrous structure of the physiological cups and the way the nerve fibers are being destroyed, I believe that cupping may not be occurring in glaucoma.
My next dilemma: if cupping is not occurring then what may be happening to the optic disc in glaucoma? Since the peripheral and arcuate fibers are always destroyed in the early stages of glaucoma, I focused my research as to why these fibers are destroyed as such in both HTG and NTG. My research, based on the glaucomatous field defects, led me to a hypothesis that the optic disc may be sinking and as a result the nerve fibers along with its vasculature are being severed in glaucoma.
Do we have evidence of severance of nerve fibers? I believe we have ample evidence that nerve fibers are being severed, not atrophied in glaucoma. Sloping/kinking of blood vessels at the disc margin in the glaucomatous disc, prior to any change in contour of physiological cup, suggests that the optic disc may be sinking in glaucoma. Excavation or empty spaces occurring in the glaucomatous disc can only be explained due to severance of the nerve fibers, not due to their atrophy. Wedge shaped defects in the retina in glaucoma can only be explained by severance and thus disappearance of the arcuate fibers, not due to their atrophy. The occurrence of notching in the superior and inferior part of the physiological cup may be due to severance and depletion of the arcuate fibers at the point of their entrance in the disc. Vertical enlargement of the physiological cup may not be a risk factor but representing cases in which glaucoma has already been initiated. Splinter hemorrhages at the disc margin, characteristic whitish pallor and absence of smaller vessels around the glaucomatous disc may be due to severance of smaller blood vessels, a fate similar to that of nerve fibers. Nasal shifting of the central vessels appears to be due to loss of anchorage due to severance of temporal fibers. Analogy: if the roots were cut from one side the tree would shift to other side. Finally, the end-stage glaucomatous disc may not be a 100% cupped atrophic disc but a crater left over after severance of all nerve fibers. Glaucoma may not be an optic disc neuropathy but an optic disc axotomy.
Is glaucoma really a neurodegenerative disease? Neurodegenerative diseases such as Alzheimer's disease and glaucoma are distinctively different. In glaucoma, the nerve fibers or their RGCs are being destroyed in an orderly fashion starting from the peripheral fibers and ending with the central and never being destroyed randomly as in neurodegenerative diseases. If glaucoma is a neurodegenerative disease, then our genes must first have predicted the impending glaucoma so to initiate apoptosis invariably and precisely with those RGCs which serve the peripheral vision and ending with central vision in an orderly fashion, an unlikely scenario. I don't believe our genes are smart enough to have such predictive capability. If the nerve fibers are being destroyed in an orderly fashion in glaucoma, then we should expect the mechanism for their destruction to be an orderly one as well (which can't occur in a neurodegenerative disease). The random degeneration of the neurons is the hallmark of a neurodegenerative disease. On this basis alone, glaucoma can't be a neurodegenerative disease. I can't think of any disease other than glaucoma in which a million or so nerve fibers or their neurons are being destroyed in a specific sequence and in an orderly fashion.
I believe glaucoma is being labeled as a neurodegenerative disease because of unexplained death of RGCs and of the neurons in the LGN occurring simultaneously. This can easily be explained by severance of the nerve fibers resulting in retrograde degeneration of the RGCs and Wallerian degeneration of the neurons in the LGN. RGCs may not be dying primarily due to apoptosis but secondary to severing of the nerve fibers.
Conclusion: In my opinion, the mystery of glaucoma lies in determining whether the nerve fibers are being atrophied or severed in glaucoma. The hypothesis of sinking disc/severing of the nerve fibers may be able to answer all the unanswered questions in glaucoma. All we need is to look at the glaucomatous disc in context of sinking disc and severance of the nerve fibers along with its vasculature and be able to determine the validity of my hypothesis. You will find my published articles, powerpoint slides and other articles in support of my hypothesis under the articles section. My two articles: Arcuate Field Defects in Glaucoma and Optic Disc may be Sinking in Glaucoma explain in detail my rationale for the hypothesis of the sinking disc/severing of the nerve fibers.
SYED S. HASNAIN M.D.
Glaucoma Axon Severance Hypothesis