Is the optic disc cupping or sinking in glaucoma?

1. Is the optic disc cupping or sinking in glaucoma? Syed S. Hasnain M.D. 560 W. Putman Ave # 6 Porterville CA 93257, U.S.A. www.hasnaineye.com hasnain40@sbcglobal.net Reference: Hasnain ss. Scleral edge , not optic disc or retina, is the primary site of injury in chronic glaucoma. Medical Hypotheses (2006) 67, 1320-1325

2. Abstract • The term cupping implies that the physiological cup starts enlarging in glaucoma. • The terms cupping and simple glaucoma have been synonymous since 1850’s. • This presentation is designed to determine whether the cupping is occurring or not. If not, then what may be occurring to the physiological cup. • This presentation will discuss three puzzling questions and how their answers, by deductive reasoning and photographic evidence, led to the conclusion that the optic disc may not be cupping but instead sinking in its entirety.

3. Puzzling Questions in Glaucoma • Q 1. Why do some people develop glaucoma at a normal IOP such as 15mmHg, while others don’t at a high IOP such as 30mmHg ? • Q 2. Why are the arcuate fibers selectively destroyed first, whereas the macular fibers last until the end stage of glaucoma? • Q 3. Why can’t we halt glaucoma in spite of maximally lowering of IOP with treatment? • This presentation would discuss above questions and their possible answers.

4. Puzzling Question 1 • Q. Why do some develop glaucoma at a normal IOP such as 15mmHg (NTG), while others not at a high IOP such as 30mmHg (Ocular Hypertension)? • History revealed that HTG patients were usually in good health whereas the NTG patients had cardio-pulmonary and circulatory problems. Interestingly, about 70% of NTG patients were long-term smokers. Thus, glaucoma may be a multifactorial disease. More the risk factors present, higher the likelihood of glaucoma akin to ischemic heart disease. This may be the answer to puzzling Q 1. • Above raises another question: If HTG is an ocular disease and NTG a systemic disease then why are there similar arcuate field defects in both HTG and NTG ? • In order to answer the above question we have to find out why and how the arcuate fibers are being selectively destroyed first. We will now discuss the puzzling Q 2.

5. Can arcuate fibers be selectively destroyed if ‘cupping’ is occurring? • Not likely. Physiological cup is the base left over after the atrophy of the Bergmeister’s papilla and is made of fibrous tissue, not elastic. First why should raised IOP enlarge physiological cup concentrically? However, if cupping ( enlargement of the cup) is due to high IOP then why is there no cupping in acute glaucoma whereas present in NTG? • How is it possible that glaucomatous cupping involving 360 degrees of disc would selectively destroy the arcuate fibers and not encompass the rest? If the above is not possible then cupping may not be occurring. Outer dotted circle depicting enlargement of the physiological cup.

6. Puzzling Q 2. Can the arcuate fibers while in the optic disc be selectively destroyed by any cause? • Unlikely. How is it possible that high IOP, or in fact any pathology, can selectively and precisely destroy the arcuate fibers among the million or so densely packed nerve fibers in the 1.5mm size optic disc? • If above is not possible, then the optic disc may not be the primary site of injury. • If the optic disc is not the primary site of injury then the terms cupping and cup/disc ratio would become invalid and misleading in evaluation of glaucoma.

7. Can the arcuate fibers while in the retina be selectively destroyed by any pathology? • Unlikely. How is it possible that IOP or in fact any pathology can selectively and preciselydestroy the arcuate fibers while they are in the retina? • Regarding apoptosis: How is it possible that apoptosis would initiate selectively and precisely only with those ganglion cells of the retina which serve the arcuate nerve fibers? • If the above scenarios are not possible then the retina may not be the primary site of injury. • Based on arcuate field defects, if the optic disc or retina cannot be the primary site of injury then what may be the site of injury? we are left with the circular border tissue.

8. Can border tissue be the site of injury? • Circular border tissue cushions between the optic disc and scleral edge (rim), and secures the optic disc in place. • Border tissue is exclusively supplied by short posterior ciliary arteries directly or via circle of Zinn-Haller. • Normally, the IOP should be lower than the arterial pressure of the border tissue for its healthy maintenance and survival. • This delicate balance would be reversed either by increase in IOP or due to decrease in arterial pressure of the border tissue as a result of poor systemic circulatory problems. In the latter scenario, even the normal IOP would become high for that poorly perfused and reduced arterial pressure of the border tissue.

9. Simulation: Border Tissue of Elschnig Circular Border tissue (green) lies between the optic disc and the scleral edge (rim). Border tissue acts as a cushion and also secures the optic disc in the scleral opening

10. What happens if the border tissue atrophies? • Optic disc would become loose and begin to sink in the scleral foramen. • Analogy: A road made of nerve fibers which converge on the manhole cover in a road as the retinal nerve fibers converge on the optic disc. • If the manhole cover begins sinking in its entirety due to deterioration of adherent material circumferentially , the ‘road nerve fibers’ would be stretched and severed at the edge. • Likewise process of sinking and severing of the RNF’s may be occurring to the optic disc in glaucoma.

11. Analogy: Sinking Manhole Cover to glaucomatous optic disc Normal: Manhole cover flush with the road. If the course of blood vessels crossing disc margin is straight then there is no sinking or no glaucoma. Early Stage glaucoma : Kinking of the blood vessels at the margin due to sinking Final Stage: Total loss of optic disc. Optic disc area becomes an empty crater. Only larger blood vessels remain at the rim. Middle Stage: Loss of temporal fibers and more kinking of the bl. vessels

12. We come back to puzzling question No. 2: Can the arcuate fibers be selectively destroyed if the optic disc is sinking? Likely:As hypothesized in following diagram. Arcuate fibers Macular fibers Macular fibers Arcuate fibers Due to temporal sinking (green arrows) all the temporal fibers which include sup. and inf. arcuate and macular fibers would be severed simultaneously. However, arcuate fibers being fewer in number, therefore they would be depleted earlier giving rise to double arcuate field defects whereas the macular fibers being abundant would last till the end stage of glaucoma. Concurrent severing of the macular fibers is revealed by loss of ganglion cells of the macular area by OCT. Double arcuate field defects. This may be the answer to the puzzling question number 2. Why are the arcuate fibers selectively destroyed first in glaucoma?

13. What may happen as the sinking of the disc continues? • Retinal nerve fibers anchor the optic disc in place as roots anchor a tree. • As the nerve fibers are being severed and depleted, the optic disc becomes more loose and sinks further resulting in severing of more nerve fibers. • This creates a self-propagating cascade of loosening and sinking which would continue until all the nerve fibers are severed at the edge. Glaucoma can’t be halted; akin to a sinking ship. This may be the answer to the puzzling Q 3. that once the glaucoma is initiated it can’t be halted. • Optic disc area becomes an empty crater after severance of all the axons (axotomy) of the optic disc.

14. Analogy: Sinking manhole cover to a glaucomatous disc Early stage glaucoma: Splinter hemorrhage at 7 o’clock. Kinking and sloping of the blood vessels at the margin. Physiological cup is still intact. Arcuate field defect present. Temporal part pale and sunken due to thinning of RNFL. Normal: Manhole cover flush with the road. Blood vessels are straight at the margin of the disc. If there is no sloping or kinking of blood vessel at the margin, then there is no sinking of the optic disc therefore no glaucoma. Late stage glaucoma: Physiological cup is broken ( de-cupping ) due to confluence of cup’s usual pallor with pallor produced by the destruction of nerve fibers in the peripheral part. Nasal shifting of vessels from loss of anchorage due to loss of temporal nerve fibers. End stage glaucoma: Total loss of the optic disc due to axotomy of the axons. Disc area becomes an empty crater. Only the larger blood vessels remain at the rim of the scleral opening.

15. Points against cupping of optic disc • Cupping implies that the physiological cup starts enlarging concentrically. Cupping, occurring concentrically, cannot selectivelyandprecisely destroy only the arcuate fibers among the million or so densely packed nerve fibers in 1.5 mm size optic disc. • If cupping is indeed occurring then those born with large cups (e.g. 0.8) would become blind sooner than those born with 0.2 cups. But this is not the case. • Fibers for the central vision are located in the central part of the disc and also superficial (closer to the vitreous). If cupping were occurring then these fibers should be destroyed first but opposite is the case since the deeper peripheral vision fibers are destroyed first in glaucoma. • Cupping occurring concentrically can’t explain the nasal shifting of the central vessels.

16. Points in favor of sinking of the optic disc. • Sinking may explain the severing of the peripheral vision fibers earlier since they are located deeper and closer to the scleral edge (rim) • Sinking may explain double arcuate field defects. • Sinking of the optic disc may explain the nasal shifting of the blood vessels due to loss of anchorage from severance of temporal fibers. • Sinking may explain the splinter hemorrhage due to severing of the smaller blood vessels at the scleral rim. • Sinking may explain progressive thinning of RNFL as revealed by OCT due to continuous severing of the nerve fibers. • Sinking may explain sloping and kinking of the blood vessels at the entire disc margin occurring prior to any change in the contour of the physiological cup. • Sinking would become self-propagating resulting in severing of the nerve fibers (axotomy) until all the axons are finished and the disc area becomes an empty crater—this is what revealed by its histology.

17. Simulation: Normal & Sinking Disc • Upper Diagram: Normal disc. Arrangement of nerve fibers in the retina & optic disc. • Lower Diagram: Glaucomatous. As the disc (yellow) sinks, the deeper peripheral fibers are stretched and severed at the edge and thus the central fibers move closer to the edge. Therefore, the peripheral fibers are severed first and the central fibers at the last. Macular( Black) Macular Arcuate Arcuate A Arcuate Nasal Arcuate Arcuate Scleral Edge Border Tissue Normal arrangement of nerve in the optic disc. Macular Nasal Scleral Border Tissue Scleral edge Sclera Black arrows showing central fibers moving closer to the edge as the peripheral fibers are being severed and depleted.

18. Patient A: Early Stage Sinking Disc • No change in size of physiological cup. • Prominent temporal scleral rim due to thinning of RNFL. Temporal area sunken and pale due to destruction of nerve fibers and its vasculature. • Sloping of vessels due to sinking and splinter hemorrhage at 7 o’clock due to severing of smaller blood vessels.

19. Middle Stage: Sinking Disc • Original cup is broken (de-cupping) due to merging of its usual pallor with the pallor produced by destruction of nerve fibers and its vasculature. • Prominent scleral edge due to thinning of RNFL. • Absence of smaller blood vessels between 7 to 9 o’clock after being severed. • Arcuate field defect present in this case.

20. Final Stage: Sinking Disc • Optic disc area is pale and shallow ( crater formation) due to loss of nerves and vasculature. • Entire scleral opening is visible due to loss of disc. • Nasal shifting of vessels due to loss of anchorage from temporal fibers. • Marked kinking of vessels at the edge due to loss of underlying nerve fibers.

21. Final Stage: Uniform Sinking • Right Eye: unusual case. No nasal shifting of central vessels due to uniform loss of anchorage provided by RNF’s 360 degrees as a result of flat insertion of the optic disc in the scleral foramen. Unusual scenario.

22. Conclusion Based on Sinking • Optic disc may not be cupping in glaucoma. • Optic disc may be sinking in its entirety in glaucoma. • Normal tension glaucoma may be a systemic disease. • Glaucoma is a multifactorial disease. More the risk factors present, higher the likelihood of development of glaucoma akin to ischemic heart disease. • The nerve fibers are not being atrophied but severed (axotomy) and depleted. At the end stage, entire disc is perished. This is what the histology of the end-stage glaucomatous disc revealing– an empty crater without disc. • Glaucoma a mechanical disease (herniation of the optic disc)? Treatment? Find ways to stabilize the sinking disc.