GEORGE L. SPAETH, MARY LUCY How does resetting MARQUES PEREIRA intraocular pressure help optic nerve function? There are two quite separate parts of this article: presumed normal in whatever is being the first deals with fact, the second, theory. The considered: disc topography, electrical subject is whether a resetting of the level of responsiveness, visual field, etc. But it should be intraocular pressure (lOP) has a beneficial effect stressed that the relationship between the in glaucoma, and if so, how it causes a benefit. different measures is complex: the disc can Regarding fact, it has been known since 1869 'improve' topographically at the same time as that lowering lOP can benefit a person - such as the visual field is deteriorating, and the disc Katherina - with glaucoma, in whom may seem structurally unchanged despite disappearance of headache and improvement in improvement in the visual field. appearance of the optic nerve head were the consequence of lowering pressure.1 It is now Evidence that glaucoma improves when lOP is known that 'improvement' in disc topography lowered is a common occurrence following lowering of the IOp,l-12 and that improvement in visual Optic disc topography function also occurs.5,13-22 This is established An improvement in the appearance of the optic fact. Much, however, is not established: disc of humans, manifested by a decrease in the diameter of the cup, shallowing of the cup, • In whom will such improvement occur? decrease in cup volume, widening of the neural • What predisposes to such improvement? rim, and a decrease in signs of venous stasis, • What are the mechanisms that account for can occur consequential to lowering IOPS.2-12 the improvement? Such improvement is common, indeed routine, Evidence of improvement is seen both in in infants with cupping caused by elevated individuals and in populations. The intraocular pressure,23,24 but it also occurs in 1,2). improvement caused by lowering lOP from adults, including the elderly (Figs. Factors 80 mmHg to 15 mmHg, in a person in whom associated with such an improvement suggest 3). lOP acutely went from 15 to 80 mmHg, is mechanisms to account for the change (Table obvious to all. But the matter to be considered The appearance of the disc varies25 and is here is whether lowering lOP is of benefit in related to its diameter (the circumference of the chronic glaucoma with lesser magnitudes of scleral ring), the anterior-posterior position of pressure elevation. Let us define our terms so the lamina, the curvature of the lamina, the we can communicate most clearly: number and size of the optic neurons, the amount and nature of other cellular material Glaucoma is ocular tissue damage at G.L. Spaeth Glaucoma (astroglia), the extracellular material and the M.L. Marques Pereira least partly related to pressure within the eye. vascularity (Table 2). William and Anna Goldberg This is an arbitrary definition, but if the Glaucoma Service The position of the anterior portion of the & pressure-related aspect is removed, every case Research Laboratories optic nerve is a function of the pressure within of an optic neuropathy becomes glaucoma. If Wills Eye Hospital the eye anterior to the lamina cribrosa, the Philadelphia loss of function must be present to have pressure posterior to the lamina cribrosa, and Pennsylvania, USA 'glaucoma' one eliminates the evolving stages of the compliance of the lamina cribrosa. The disc the disease, and considers only the late stages of G.L. Spaeth is a plastic structure, related to the presence of the condition, because topographical change Professor of Ophthalmology elastin in the lamina. With increasing age the Jefferson Medical College precedes functional change. amount of elastin decreases. Also, the nature of Philadelphia A careful distinction must be collagen changes with age and perhaps with PA 19107, USA Improvement the made between an improvement in a finding and presence of glaucoma?6-29 Changes in lOP, George L. Spaeth, MD � an improvement in function, cellular or then, either up or down, can be associated with Wills Eye Hospital personal. These are related, but different changes in the position of the lamina 900 Walnut Street measures. For example, the rim area of the disc cribrosa.30-33 In the enucleated eye, raising lOP Philadelphia 5 50 PA 19107, USA may become thicker or the cup shallower, but from to mmHg displaces the surface of the that does not prove that neurones function optic nerve head 36 fLm posteriorly.31 As the Tel: +1 (215) 928 3197 Fax: +1 (215) 928 0166 better or that the person sees better. By lamina moves anteriorly or posteriorly, it has e-mail: [email protected] 'improvement', here, we mean a return towards the capacity to traumatise neurones directly by 476 14, 476-487 Eye (2000) © 2000 Royal College of Ophthalmologists (a) (b) Concentric cupping becoming worse with [OP near 40 mmHg Fig. 1. (a, b), but becoming less post-operatively when [OP pressure was 18 mmHg (c, taken years after b). (c) 2 compression injury or traction on straight or kinked The size of the optic cup is related to the size of the neurones,34 or indirectly due to arterial ischaemia or optic nerve head.43 A decrease in the size of the scleral venous stasis.35-42 Lowering lOP, then, may presumably ring, with a consequent decrease in the diameter of the exert a beneficial effect if the anterior optic nerve has optic nerve head, can occur, especially in infants, been posteriorly displaced secondary to lOP. The following lowering of lOP?3 Thus, improvement in disc absolute level of lOP may be immaterial. The critical topography in infants following a decrease in lOP is a factors are the relationship between the level of lOP combination of anterior movement of the lamina and a anterior to and posterior to the lamina, and the ability of decrease in disc size. This mechanism has not been that lamina to be deformed due to its compliance extensively studied in adults, but is certainly less of a characteristics. Laminar deformation may also have factor than in infants. effects on the vessels that pass through the tissues, and a The width of the neural rim of the optic nerve is a restoration of the normal position of the lamina may be function of the size of the scleral ring and the number associated with improved haemodynamics, assuming and nature of the neurones. The scleral ring can be vascular changes are not permanent. affected by lOP, as already discussed.23 Most normal (a) (b) (a), (b) The optic disc of this 60-year-old man showed less cupping following reduction of [OP (b). Fig. 2. 477 Factors predisposing to improvement of optic disc topography Mechanisms for improvement in disc appearance, in Table 1. Table 3. association with lowering of intraocular pressure Young age Short duration of optic disc damage Anterior displacement of lamina cribrosa Marked fall in intraocular pressure Decrease in the diameter of the disc Less advanced optic disc damage Healing of damage neurones Concentric cupping without focal change of optic disc Increase in connective tissue (late) Oedema (early and transient) Oedema (chronic with hypotony) eyes have roughly the same number of optic neurones; Neogenesis of neurones this number decreases with age.44-47 The neural ring may become thinner in advancing age because of this been established that lowering lOP by, for example, apparently obligatory loss of neurones, although this 15 mmHg is more beneficial in a particular specific change, if real, is not marked.48 It is logical to assume that population or particular individual than lowering lOP by damaged neurones that recover when the damaging 5 mmHg. It is also not known whether considering the factors are relieved may regain their normal bulk, and, as lowering in terms of a percentage of absolute fall is more such, cause a thickening of the neural rim. relevant. However, improvement appears to be unlikely Astroglia comprise a portion of the optic nerve head when lOP falls by less than 30%.5 One study, which tissue.49 These cells are also damaged by factors that affect reviewed stereophotographs and visual fields, the neurones.50 As they recover, which they presumably demonstrated that of patients having at least a 30% do when damage is not fatal, they may cause a decrease in cupping. In patients with far-advanced damage such a reduction in lOP, 30% had improved disc appearance 5 change appears to occur occasionally, as demonstrated by and 40% had improved visual fields. In another study, a marked 'filling in' of the cup, usually unassociated with using computer analysis of optic disc stereophotographs, improvement in visual function (Fig. 3). improvement in all optic disc parameters was found in 8 6 Acute oedema may cause an immediate decrease in of 13 eyes having a mean lOP reduction of 48%. Using 'cupping' following a decrease in lOP (Fig. 4). While this the same technique another study detected increased tends to be more prominent in eyes with lesser degrees of neuroretinal rim area in 44% of patients undergoing disc change, it can occur in eyes with advanced optic glaucoma surgery? Raitta and colleagues6 showed, using nerve damage.51 the Heidelberg Retina Tomograph (HRT) to study Lastly, the possibility of neuronal neogenesis can no changes in optic disc topography after glaucoma surgery longer be dismissed, since several investigators have in 9 patients, a reduction in optic disc cup volume in all now established that central nervous systems neurones but one of the eyes that had at least a 30% lOP reduction. 5 53 can regenerate. 2, This, however, is not a likely The mean cup depth was reduced significantly for this explanation for the topographic improvement in adults.