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Should antiproliferatives be used in filtering surgery of normal tension glaucoma?
  1. ALBERT ALM
  1. Department of Neuroscience, Ophthalmology, University Hospital, S-701 85 Uppsala, Sweden albert.alm{at}nc.uas.iul.se

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The overall goal for all glaucoma treatment is to preserve useful vision. Thus, the two most important tasks for the ophthalmologists are to determine the rate of progression in each case and, if necessary, to slow it down sufficiently to reach the overall goal. It may not be possible to arrest progression completely since elderly patients with moderate visual field loss probably have lost most or all of their “reserves” owing to a combination of glaucomatous damage and natural loss of ganglion cells. In such eyes even the continuous natural loss of ganglion cells may manifest itself as a slow progression of the visual field defect, but hardly at a sight threatening rate.

How should this goal be achieved? Although it is generally accepted that open angle glaucoma is a multifactorial disease the intraocular pressure (IOP) is still the only known treatable risk factor. Several studies have shown that the IOP is a graded risk factor where the risk of diagnosing a damaged optic nerve increases with the level of the IOP, even within the normal range of IOP.1 ,2 Considering that more than 90% of the population have an IOP below 22 mm Hg it is no surprise that many eyes with a glaucomatous damaged optic nerve have a normal IOP—normal tension glaucoma (NTG). These patients pose a clinical challenge to all ophthalmologists.

The first question is of course if they should be treated or not. We assume, based on clinical experience, that there is a relation between the pressure level and the rate of progression. This is supported by data from the Normal Tension Glaucoma Study,3 where a large number of patients did not progress during 5–8 years' follow up even if they received no treatment. Thus, one can expect that in many, but not all, cases of NTG the overall goal is reached even if no treatment is instituted.

When treatment is initiated filtering surgery is often considered as an effective means of reducing the IOP. As the IOP is already within the normal range one cannot expect a substantial reduction of the IOP with drug treatment in most patients. Most drugs exert their effect not on the IOP but on the outflow pressure—that is, the IOP less the episcleral venous pressure. With an episcleral venous pressure of about 8 mm Hg4 even a 30% reduction of aqueous flow would only reduce IOP about 3 mm Hg in an eye with an IOP of 18 mm Hg. This is barely above the measurement error of 2 mm Hg.5 In a retrospective analysis of 291 medical records of patients with an IOP of 21 or less at diagnosis, 173 (60%) had an effect with a non-selective β blocker that was less than 3 mm Hg6—that is, within the measurement error. At the end of a 2 year follow up the average IOP reduction in these patients was 13%, from 18.6 to 16.2 mm Hg.6 It is obvious that for a large number of these patients treatment could not have made much difference to the progression rate. But there is no doubt that treatment for NTG is mandatory if the progression rate threatens to produce a visual handicap.

Data have been presented supporting the fact that pressure reduction does slow down the rate of progression even in NTG.3 ,7 A substantial pressure reduction is difficult to achieve without filtering surgery. Still, even in the best hands filtering surgery is not without risk. Neither is filtering surgery a definite procedure. In many patients the filter fails within a few years. Antiproliferatives have increased the odds of retaining the pressure reduction after filtering surgery, and in this issue of theBJO (p 696) Membrey and co-workers report their experience with filtering surgery with or without antiproliferatives in NTG in a retrospective analysis. In an attempt to improve the chances of retaining a good pressure reduction a guarded fistulising procedure was performed. The choice of using antiproliferatives followed the evolved policy in the clinic. In 1992 peroperative 5-FU was introduced and in 1995 peroperative mitomycin C (MMC). The retrospective analysis showed a 50% reduction of the relative risk of progression in patients with an IOP reduction of at least 30% compared with patients with no change in IOP. The analysis also showed that even though the MMC group had the best IOP reduction, the 5-FU group fared better because of late complications, including late hypotony, in the MMC group. The experience that the benefits of MMC in NTG can be outweighed by postoperative sight threatening complications has been reported previously.7 ,8Interestingly, when corrected for the reduction in IOP the group receiving no antiproliferatives tended to have the best outcome, but when compared with the 5-FU group the better pressure control in this group outweighed that advantage. The results indicate that we have yet to find the ideal drug to enhance the chances of a permanent effect of fistulising surgery. With the choices available today the authors conclude that a guarded procedure including peroperative 5-FU is the procedure of choice when filtering surgery is indicated for NTG.

References

Narrative Based Medicine, An Interdisciplinary Conference Research, Narrative, and Practice A two day conference—Monday 3rd and Tuesday 4th September 2001 Homerton College, Cambridge, UK

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