2
as atropine penalisation have received limited attention. More recently short term trials of the dopamine agonist levodopa showed significant but transient improvements in acuity (Bas- mak et al., 1999), which were similar to those reported following administration of cytidine- 5-diphosphocholine therapy (Porciatti et al., 1998). These treatments have yet to achieve acceptance with either patients or practitioners, and currently occlusion therapy following removal of the initial visual insult remains the standard treatment for amblyopia. References Attebo, K., Mitchell, P. and Cumming, R. (1998). Prevalence and causes of amblyopia in an adult population. Ophthalmology 105, 154–159. Basmak, H., Yildirim, N., Erdinc, O., Yurdakul, S. and Ozdemir, G. (1999). Eect of levodopa therapy on visual-evoked potentials and visual acuity in amblyopia. Ophthalmologica 213, 110–113. Porciatti, V., Schiavi, C., Benedetti, P., Baldi, A. and Campos, E. C. (1998). Cytidine-5-diphosphocho- line improves visual acuity, contrast sensitivity and visually-evoked potentials of amblyopic subjects. Current Eye Res. 17, 141–148. # 2000 The College of Optometrists. Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain 0275-5408/00/$20.00 + 0.00 PII: S0275-5408(99)00074-5 Chemical modulation of the vitreous: a novel approach for the new millennium David McLeod Academic Department of Ophthalmology, Royal Eye Hospital, Oxford Road, Manchester, UK Thirty years ago Dr Robert Machemer introduced ‘‘vitrectomy via the pars plana’’ whereby the vitreous gel is mechanically disrupted prior to its aspiration from the eye. This approach has been successfully adopted for an ever-increasing spectrum of pathologies ranging from vitreous opacification, through complex retinal detachments (especially those with fibrosis on the retina) to, most recently, macular surgery. These developments have depended on improved instrumentation (e.g. microscissors for removal of fibrotic membranes), on serendipitous recognition of treatability (e.g. surgery for macular holes) or on ‘‘boldly going where no man has gone before’’ (e.g. surgical relocation of the macula). The introduction of other physical devices such as the endolaser was also a major step forward but, to date, laser disruption of the vitreous and fibrotic membranes has proved disappointing. Diculties remain in completely removing the gel especially where it is firmly attached to the retina; the forces required to separate the gel from attached retina may result in nerve- fibre damage or in retinal break formation, while separation of gel from detached retina is practically impossible and this frequently compromises surgical outcomes. Attempts have therefore been made to devise alternative means of breaking down the vitreous and associated fibrous tissue, not least by the injection of proteases or glycosidases into the vitreous (Bishop et al., 1999). However, such an enzymatic attack on the strong covalent bonds within and between molecules can bring attendant problems of collateral damage. For these reasons, we have been seeking to devise safer and more precise chemical means of modulating the gel structure. This research is predicated on the hypothesis that the corpor- E-mail address: [email protected] (D. McLeod). S16 Ophthal. Physiol. Opt. 2000 20: No 2

Chemical modulation of the vitreous: a novel approach for the new millennium

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as atropine penalisation have received limited attention. More recently short term trials ofthe dopamine agonist levodopa showed signi®cant but transient improvements in acuity (Bas-mak et al., 1999), which were similar to those reported following administration of cytidine-5-diphosphocholine therapy (Porciatti et al., 1998). These treatments have yet to achieveacceptance with either patients or practitioners, and currently occlusion therapy followingremoval of the initial visual insult remains the standard treatment for amblyopia.

References

Attebo, K., Mitchell, P. and Cumming, R. (1998). Prevalence and causes of amblyopia in an adultpopulation. Ophthalmology 105, 154±159.

Basmak, H., Yildirim, N., Erdinc, O., Yurdakul, S. and Ozdemir, G. (1999). E�ect of levodopa therapyon visual-evoked potentials and visual acuity in amblyopia. Ophthalmologica 213, 110±113.

Porciatti, V., Schiavi, C., Benedetti, P., Baldi, A. and Campos, E. C. (1998). Cytidine-5-diphosphocho-line improves visual acuity, contrast sensitivity and visually-evoked potentials of amblyopic subjects.Current Eye Res. 17, 141±148.

# 2000 The College of Optometrists. Published by Elsevier Science LtdAll rights reserved. Printed in Great Britain

0275-5408/00/$20.00+0.00

PII: S0275-5408(99)00074-5

Chemical modulation of the vitreous: a novelapproach for the new millenniumDavid McLeod

Academic Department of Ophthalmology, Royal Eye Hospital, Oxford Road, Manchester, UK

Thirty years ago Dr Robert Machemer introduced ``vitrectomy via the pars plana'' wherebythe vitreous gel is mechanically disrupted prior to its aspiration from the eye. This approachhas been successfully adopted for an ever-increasing spectrum of pathologies ranging fromvitreous opaci®cation, through complex retinal detachments (especially those with ®brosis onthe retina) to, most recently, macular surgery. These developments have depended onimproved instrumentation (e.g. microscissors for removal of ®brotic membranes), onserendipitous recognition of treatability (e.g. surgery for macular holes) or on ``boldly goingwhere no man has gone before'' (e.g. surgical relocation of the macula). The introduction ofother physical devices such as the endolaser was also a major step forward but, to date, laserdisruption of the vitreous and ®brotic membranes has proved disappointing.Di�culties remain in completely removing the gel especially where it is ®rmly attached to

the retina; the forces required to separate the gel from attached retina may result in nerve-®bre damage or in retinal break formation, while separation of gel from detached retina ispractically impossible and this frequently compromises surgical outcomes. Attempts havetherefore been made to devise alternative means of breaking down the vitreous and associated®brous tissue, not least by the injection of proteases or glycosidases into the vitreous (Bishopet al., 1999). However, such an enzymatic attack on the strong covalent bonds within andbetween molecules can bring attendant problems of collateral damage.For these reasons, we have been seeking to devise safer and more precise chemical means

of modulating the gel structure. This research is predicated on the hypothesis that the corpor-

E-mail address: [email protected] (D. McLeod).

S16 Ophthal. Physiol. Opt. 2000 20: No 2

Page 2: Chemical modulation of the vitreous: a novel approach for the new millennium

ate integrity of the vitreous re¯ects its collagenous framework with its non-covalent inter-actions. Thus, the gel, which is subject to liquefaction during ageing, may be amenable tonon-enzymatic dissolution using chemical moieties which competitively inhibit and disruptthe (multiple but weak) non-covalent bonds between the molecules. An alternative approachmight be to so modulate the gel that it resists age-related liquefaction so posterior vitreousdetachment is delayed and consequent retinal tears and detachment are prevented. Moreover,the vitreous cortex might be modi®ed so that proliferation of aberrant networks of preretinalnew vessels and sheets of ®brous tissue in diabetes are prevented; we already know that, inthe absence of attached cortical gel, development of proliferative diabetic retinopathy is lar-gely precluded (Wong et al., 1989).Crucial to the successful implementation of this strategy is the identi®cation of the key

structural molecules in the vitreous and their non-covalent interactions. To this end ourresearch group, led by Mr Paul Bishop, has extended knowledge on a number of fronts e.g.the recent discovery of the proteoglycan versican in vitreous (Reardon et al., 1998). Mostrecently, a novel collagen-associated leucine-rich repeat protein, which we have called opticin,has been identi®ed (Reardon et al., 2000). Ongoing studies are examining the role of thesemolecules in the structural assembly of the vitreous and their relevance to our chemicalmodulation strategy.

References

Bishop, P. N., McLeod, D. and Reardon, A. (1999). E�ects of hyaluronan lyase, hyaluronidase andchondroitin ABC lyase on mammalian vitreous gel. Invest. Ophthalmol. Visual Sci. 40, 2173±2178.

Reardon, A., Heinegard, D., McLeod, D., Sheehan, J. K. and Bishop, P. N. (1998). The large chondroi-tin sulphate proteoglycan versican in mammalian vitreous. Matrix Biol. 17, 325±333.

Reardon, A. J., Le Go�, M., Briggs, M. D., McLeod, D., Sheehan, J. K., Thornton, D. J., Bishop,P. N. (2000). Identi®cation in vitreous and molecular cloning of opticin, a novel member of the familyof leucine-rich repeat proteins of the extracellular matrix. J. Biol. Chem. in press.

Wong, H. C., Sehmi, K. S. and McLeod, D. (1989). Abortive neovascular outgrowths discovered duringvitrectomy for diabetic vitreous haemorrhage. Graefe's Arch. Clin. Exp. Ophthalmol. 227, 237±240.

# 2000 The College of Optometrists. Published by Elsevier Science LtdAll rights reserved. Printed in Great Britain

0275-5408/00/$20.00+0.00

PII: S0275-5408(99)00072-1

Presbyopia Ð the whens, whys andwherefores . . .

Barbara K. Pierscionek

Department of Optometry, University of Bradford, Richmond Road,Bradford, West Yorkshire, BD7 1DP, UK

Whatever inconsistencies or di�erences have arisen between various theories of presbyopia,there is a clear understanding and united acceptance of its de®nition: presbyopia is the loss ofaccommodative function with age. Consequently, the question about when presbyopia com-mences, instinctively solicits the notion of a numerical answer in the form of a chronologicalage. The latter is always considered to be based on the manifestation of the condition Ð thenearest point of clear vision.

E-mail address: [email protected] (B.K. Pierscionek).

Conference 2000 Abstracts S17