British Journal of Ophthalmology

Editorials
Leprosya new look at an old disease
Leprosy is one of the oldest scourges of humankind.
Accurate portrayals of the disease in Chinese medical
treatises date from 400 BC, and classic descriptions in
ancient Indian literature occur even earlier.
1
In our west-
ern tradition the fear and loathing directed towards the
disease come directly from the bible. Leprosy was the
disease of the soul, the punishment for sin. By the
dawn of the Middle Ages the leper had become the
universal symbol of persecution, the diseased and
disenfranchised outcast of Western society.
2
Even though
the prevalence of leprosy steadily declined in Western
Europe after a peak in the 14th century, it became
epidemic in other parts of the world, especially in Asia,
Africa, and South America. Until the introduction of dap-
sone in the 1940s there was no eVective treatment for lep-
rosy, and infected individuals were routinely isolated and
segregated from all contact with society. In some areas of
the world this approach continued until well into the
1980s, even after a number of highly eVective antileprosy
drugs had been developed.
Today the prevalence of this ancient disease is rapidly
declining in most countries around the world. This
decline is a direct result of the widespread administration
by public health workers of multidrug therapy (MDT), a
combination of rifampin, dapsone, and clofazimine. The
introduction of MDT by the World Health Organization
in 1982 for the treatment of multibacillary leprosy has led
to a shortened treatment time of 2 years and a high degree
of bacterial eradication (99.9%). It is felt that MDT for 2
years in almost all cases is adequate for producing a com-
plete bacteriological cure of the disease and for preventing
the emergence of drug resistant strains of Mycobacterium
leprae.
3
In spite of this optimistic assessment leprosy still
aVects 1012 million people worldwide, the majority of
whom are found in Africa and in the southern portion of
the Indian subcontinent.
4
The disease invariably causes
many visually disabling sequelae, and it is estimated that
3.2% of all leprosy patients are ultimately blinded by long
term ocular complications.
5
Several recent studies have
documented the main causes of blindness in leprosy.
4 512
These causes include iritis, posterior synechia, cataract,
lagophthalmos, corneal ulceration, and all of the compli-
cations associated with corneal hypaesthesia and expo-
sure. However, none of the studies has addressed the
question of whether or not the sight threatening
complications of leprosy continue to develop after the
infectious component of the disease has been adequately
treated.
We have had a highly eVective treatment programme for
leprosy for almost 20 years, and the treatment regimen,
MDT, has been proved to be almost 100% eVective in
eliminating M leprae in infected patients. But the ocular
complications of the disease remain a major cause of
blindness worldwide, and we still do not understand how,
why, or to what extent eye disease in cured leprosy
patients continues to progress. Until we understand this
phenomenon we will not be able to adequately address the
eyecare needs of leprosy patients.
Lewallen et al (see p 817, this issue) have examined
this question in an exhaustive study that spans an
11 year period from 1988 to 1999 and documents
ocular changes in leprosy patients in eight resettlement
villages in South Korea. Of 501 patients examined in 1988
the authors were able to nd 270 for re-examination in
1999, a remarkable follow up eVort. Eighty four of the
patients had died. It is known that patients who are blind
from leprosy have a 4.8-fold excess risk of death compared
with their non-blind peers of the same age.
13
Lewallen and
colleagues found that, over the 11 year period, of the
patients with no sight threatening leprosy related ocular
diseases (lagophthalmos, posterior synechia, keratitis, etc)
in 1988, 14.7% had developed one or more of these
conditions in 1999. Similarly, of those with no signs
of cataract in 1988, 26.4% had developed a vision
reducing cataract in at least one eye at the follow up
examination. Overall, 14.3% of the patients developed
visual impairment and 5.7% became blind in the
intervening 11 years.
These ndings are a sobering reminder that even
though patients may be cured bacteriologically, leprosy
related ocular lesions can slowly cause visual impairment
that ultimately leads to blindness. Lewallen et al did not
nd any ocular lesions caused by active infection by M
leprae. Instead, they found that progressive visual loss
occurred as a result of chronic nerve damage that
led to lagophthalmos, entropion, ectropion, corneal
exposure, and keratitis. Small pupils, posterior synechia,
and cataracts were frequently associated with a smoulder-
ing chronic iritis. This phenomenon has been com-
monly described in cured leprosy patients and is felt to
be caused by damage to the sympathetic nerves.
Therefore, Lewallen et al concluded that all of the
progressive long term blinding complications in these
bacteriologically cured leprosy patients, with the excep-
tion of trichiasis, were the direct result of chronic nerve
damage.
Br J Ophthalmol 2000;84:809812 809
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From a public health point of view this study documents
for the rst time the progressive nature of the blinding
complications of leprosy long after a cure has been
eVected. This conclusive evidence should have a profound
inuence on the planning of future strategies for blindness
prevention in leprosy treatment programmes. Improved
methods for managing the ocular complications of leprosy
are currently being proposed.
14
Any future recommenda-
tions for the worldwide eradication of leprosy and the
treatment of the ocular complications of the disease should
take into consideration the ndings of this important
study.
JOHN P WHITCHER
Francis I Proctor Foundation for Research in Ophthalmology,
University of California San Francisco, San Francisco, CA
941430944, USA
[email protected]
M SRINIVASAN
Aravind Eye Hospital and Postgraduate Institute of Ophthalmology,
1 Anna Nagar, Madurai - 625020, Tamil Nadu, India
1 Ma Haide, Ye Gan-Yun. Leprosy in China. Leprosy Rev 1982;53:81.
2 Richards P. The medieval leper and his northern heirs. Cambridge: DS Brewer,
Ltd, 1977.
3 Vijay Kumaran P, Jesudasan K, Manimozhi N. Fixed-duration therapy
(FDT) in multibacillary leprosy; eYcacy and complications. Int J Leprosy
1996;64:1237.
4 John D, Daniel E. Infectious keratitis in leprosy. Br J Ophthalmol
1999;83:1736.
5 Vytche TJ. The prevalence of disabling ocular complications in leprosy: a
global study. Indian J Leprosy 1998;70:4959.
6 Malu KN, Malu AO. Blindness in leprosy patients of Kaduna State, North-
ern Nigeria. Tropical Doctor 1995;25:1813.
7 Courtright P, Lewallen S, Huan-Ying Li, et al. Lagophthalmos in a
multibacillary population under multidrug therapy in the Peoples Repub-
lic of China. Leprosy Rev 1995;66:21419.
8 Daniel E, Alexander R, Chacko S. Ocular leprosy: do steroids complicate
matters? (Letter) Int J Leprosy 1995;63:11517.
9 Waddle KM, Saunderson PR. Is leprosy blindness avoidable? Br J Ophthal-
mol 1995;79:2506.
10 Srinivasan H. Ocular morbidity in leprosy-aVected persons [Editorial].
Indian J Leprosy 1998;70:14.
11 Courtright P. The epidemiology of ocular complications of leprosy. Indian J
Leprosy 1998;70:337.
12 Knuttila JP, van Brakel WH, Anderson AM. Ocular impairments in an
impairment survey of leprosy-aVected persons in Nepal. Leprosy 1998;70:
936.
13 Courtright P, Kim SH, Lee HS, et al. Excess mortality associated with
blindness in leprosy patients in Korea. Leprosy Rev 1997;68:32630.
14 Hogeweg M. Strategies for improvement of ocular complications in leprosy.
Indian J Leprosy 1998;70:6170.
Entry site neovascularisation after diabetic vitrectomy
When scleral entry sites over the pars plana were rst
used for vitrectomy access, concerns were raised that
anterior vitreous complications might compromise
surgical outcomes.
1 2
After all, it had long been recognised
that, in chronic uveitis or in inammation complicating a
penetrating injury, the non-pigmented ciliary epithelium
might undergo proliferation and brous metaplasia,
accompanied by a stroma derived vascular component, to
form a cyclitic membrane using the anterior surface of
the vitreous as a scaVold; this could lead to traction on the
ciliary processes and peripheral retina, hypotony, and
phthisis.
3
The retrolental membrane might also include
glial and retinal pigment epithelial cells in cases of
concomitant rhegmatogenous retinal detachment or an
ingrowth of episclera derived brovascular tissue at
sites of penetration. Happily, such foreboding over
pars plana vitrectomy has proved largely unfounded,
presumably reecting in part the dispersion of any
inammatory mediators involved. But vitrectomy for
the ischaemic retinopathies, especially for proliferative
diabetic retinopathy (PDR), has been a notable
exception.
Following vitrectomy for PDR, any residual new vessels
located posterior to the vitreous base usually undergo
regression,
4
but some eyes develop orid basal neovascu-
larisation as a supplement to the normal wound healing
process at the sclerotomies.
2 5 6
Such entry site neovascu-
larisation (ESNV) may arise as an isolated event after oth-
erwise successful surgery when it represents one of a
number of possible sources of delayed diabetic vitreous
cavity haemorrhage (DVCH)that is, bleeding after an
initial haemorrhage-free period of 3 or more weeks
post-vitrectomy. Other possible culprits for delayed
DVCH include secondary haemorrhage from shedding
of thrombus (for example, from a sclerotomy or from a
retinal vein from which a neovascular outgrowth had been
avulsed during vitrectomy) or detachment of residual
attached post-basal cortex and avulsion of brovascular
tissue contained therein. The mechanism of bleeding from
ESNV (that is, whether through some mechanical event or
simply as a manifestation of friability) is uncertain as is the
nature of its spontaneous regression.
6
In other circum-
stances, however, ESNV forms part of a more widespread
uveal proliferation involving both the iris and ciliary body
and frequently associated with retinal detachment as a
cause or consequence of the vascularised cyclitic
membrane.
1 2 7 8
The term brovascular ingrowth has been used
inadvisedly
2 6
to denote the intraocular vascularised
proliferation at sclerotomies for it implies an episcleral
contribution to, or source of, ESNV
9
(which is seldom the
case). There has also been a dearth of information regard-
ing the incidence of ESNV post-vitrectomy. Michels
4
dis-
covered only one example of ESNV within 18 months of
successful vitrectomy in an early series of 107 eyes with
PDR, most of which must be presumed to have been
aphakic; many such aphakic vitrectomised eyes
nevertheless developed rubeosis iridis, ostensibly though
removal of the hyalolenticular barrier to anterior diVusion
of cytokines and growth factors.
4 7
The source of DVCH
in eyes kept phakic in later years was seldom identied,
10 11
albeit, many surgeons believed that ESNV was a major
contributor to DVCH with consequential fears that any
additional entry sites would increase the potential for
rebleeding. However, two recent studies have provided
new insights into the contribution of ESNV to DVCH.
Firstly, Hotta and colleagues
12
found ESNV at one or
more sclerotomies in six out of 13 eyes (46%) undergoing
vitreous cavity washout (VCWO) for DVCH. Of the 12
aVected sclerotomies, 11 had shown a low reective
trapezoid image on ultrasound biomicroscopy (though
the overall predictive value of this ultrasonic feature for
ESNV was only 50%). Secondly, West and Gregor,
reporting in this issue of the BJO (p 822), found ESNV
in 11 out of 19 eyes (58%) undergoing VCWO for
DVCH. The presence or absence of an episcleral vessel
at a sclerotomy (putatively a sentinel of ingrowth)
was an unreliable predictor of ESNV and no instance
of more widespread brovascular proliferation in
the anterior vitreous, whether of cyclitic or retinal
810 Editorials
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origin, was discovered during VCWO. Vessels derived
from the anterior retina are the distinctive and
distinguishing feature of so called anterior hyaloid brov-
ascular proliferation (AHFP) which complicated vitrec-
tomy for PDR in a high proportion (13%) of a particular
series of cases.
13 14
However, such rampant retrolental
neovascularisation (RLNV),
15
apparently arising inde-
pendently of ESNV,
14 15
was probably a consequence of
concomitant scleral buckling (causing superimposed
ischaemia).
Three factors appear to be important in the pathogen-
esis of ESNV (and indeed RLNV/AHFP). Firstly,
continuing post-vitrectomy secretion of ischaemic retina
derived angiogenic growth factors is essential since ESNV
is not seen after vitrectomy for non-ischaemic pathologies.
Secondly, the presence of an intact anterior hyaloid
barrier to egress of these growth factors via the aqueous
humour is postulated,
15
at least for RLNV/AHFP. Thirdly,
a requirement for a vitreous scaVold for de novo growth of
vessels is suggested by past experience of extension of iris
neovascularisation onto the anterior hyaloid face in rube-
otic, intracapsular aphakic eyes and by analogy with
preretinal neovascularisation where the absence of a corti-
cal vitreous substrate either precludes
16
or restricts
17
new
vessel proliferation. Various preventative measures thus
arise whereby the incidence of ESNV (and DVCH) might
be reduced. The most obvious and currently applicable
approach is to undertake scatter endophotocoagulation of
all previously untreated ischaemic retina at the time of vit-
rectomy for PDR; this might logically be supplemented by
post-oral cryotherapy behind the sclerotomies and
wherever basal haemorrhagic residues or the danger of
lens damage prevents ll-in laser up to the ora serrata
through 360 degrees.
9 18 19
However, the evidence base
for the eVectiveness of such treatment is not substan-
tial. Using surrogate measures for ESNV such as the
incidence of DVCH, rubeosis, and VCWO historical
comparisons of vitrectomy outcomes have been made
before and after xenon arc
19
and later argon laser
endophotocoagulation
18 20
became available. Liggett and
colleagues
20
obtained a signicant reduction in delayed
DVCH and VCWO using an average of only 338 endola-
ser burns at the time of vitrectomy but, unless there is evi-
dence of burn out or complete scatter laser of the retin-
opathy, much more extensive treatment is generally
recommended as prophylaxis.
18
A second preventative approach to the phakic or pseu-
dophakic diabetic eye is to deliberately remove a small
portion of the anterior hyaloid during vitrectomy. This
creates the state of pseudo-aphakia whereby free
exchange of cells and solutes takes place between the
anterior chamber and vitreous cavity.
18
Just as aphakia
accelerates the spontaneous clearance (via the trabecular
meshwork) of both immediate
7 21
and delayed
7
DVCH, so
does pseudo-aphakia, whether induced intentionally or
arising incidentally (by surgical interference with the
anterior hyaloid face at one or more entry sites). A full
scatter photocoagulation (to prevent rubeosis) and
thorough clearance of inferior basal gel haemorrhage (to
prevent immediate DVCH and erythroclastic glaucoma
22
)
are essential to this strategy. Chemical modulation or dis-
ruption of the anterior vitreous scaVold for vessel
proliferation is a potential future extension of this
approach.
23
So far as management of established ESNV (and
RLNV/AHFP) is concerned, further indirect treatment
using additional scatter endolaser during VCWO
8 13 15 18
is the current mainstay is also promulgated by West
and Gregor; an attempt to establish pseudo-aphakia
should also be considered. Direct dissection of bro-
vascular membranes (necessitating lensectomy) has
previously been advocated for RLNV/AHFP complicated
by peripheral traction retinal detachment,
9 13
and a
similar method of managing extensive or persistent
ESNV was employed by West and Gregor even in eyes
without such detachment. Others have recommended
lens sparing surgery for ESNV using silicone oil
to obstruct access of growth factors to the sclerotomy
sites,
8
but reparative epiretinal brosis and retro-silicone
oil neovascularisation
15 24
are a danger. Such measures
remain to be justied by longer term follow up of
individual cases and formal comparison with more
modest approaches to DVCH uncomplicated by cyclitic
traction.
DAVID MCLEOD
Manchester Royal Eye Hospital
[email protected]
1 Buettner H, Machemer R. Histopathologic ndings in human eyes after pars
plana vitrectomy and lensectomy. Arch Ophthalmol 1977;95:202933.
2 Koch FH, Kreiger AE, Spitznas M, et al. Pars plana incisions of four
patients: histopathology and electron microscopy. Br J Ophthalmol
1995;79:48693.
3 Lee WR. In: Ophthalmic histopathology. Berlin: Springer Verlag, 1993.
4 Michels RG. In: Vitreous surgery. St Louis: CV Mosby, 1981.
5 TardiV YM, Schepens CL. Closed vitreous surgery. XV. Fibrovascular
ingrowth from the pars plana sclerotomy. Arch Ophthalmol 1977;95:2359.
6 Kreiger AE. Wound complications in pars plana vitrectomy. Retina 1993;13:
33544.
7 Schachat AP, Oyakawa RT, Michels RG, et al. Complications of vitreous
surgery for diabetic retinopathy II: postoperative complications. Ophthal-
mology 1983;90:52230.
8 Blumenkranz MS. Lens-sparing treatment of recurrent diabetic vitreous
hemorrhage associated with anterior neovascularization by silicone oil
injection, cryopexy, and laser photocoagulation. In: Stirpe M, ed. Anterior
and posterior segment surgery: mutual problems and common interests. New
York: Ophthalmic Communications Society Inc, 1998.
9 Lewis H. In: Ed Lewis H, Ryan SJ, eds. Medical and surgical retina. Chapter
28. St Louis: Mosby, 1994.
10 Tolentino FI, Cajita VN, Gancayco T, et al. Vitreous haemorrhage after
closed vitrectomy for proliferative diabetic retinopathy. Ophthalmology
1989;96:1495500.
11 Brown GC, Tasman WS, Benson WE, et al. Re-operation following diabetic
vitrectomy. Arch Ophthalmol 1992;110:50610.
12 Hotta K, Hirakata A, Ohi Y, et al. Ultrasound biomicroscopy for examina-
tion of the sclerotomy site in eyes with proliferative diabetic retinopathy
after vitrectomy. Retina 2000;20:528.
13 Lewis H, Abrams GW, Williams GA. Anterior hyaloidal brovascular prolif-
eration after diabetic vitrectomy. Am J Ophthalmol 1987;104:60713.
14 Lewis H, Abrams GW, Foos R. Clinicopathologic ndings in anterior
hyaloidal brovascular proliferation after diabetic vitrectomy. Am J
Ophthalmol 1987;104:61418.
15 Charles S. In: Vitreous microsurgery. 2nd ed. Baltimore: Williams and
Wilkins, 1987.
16 Akiba J, Arzabe CW, Trempe CL. Posterior vitreous detachment and
neovascularisation in diabetic retinopathy. Ophthalmology 1990;97:88991.
17 Wong HC, Sehmi KS, McLeod D. Abortive neovascular outgrowths discov-
ered during vitrectomy for diabetic vitreous haemorrhage. Graefes Arch Clin
Exp Ophthalmol 1989;227:23740.
18 McLeod D. Microsurgical management of neovascularisation secondary to
posterior segment ischaemia. Eye 1991;5:2529.
19 Ficker LA, Passani F, Leaver PK, et al. Xenon-arc endophotocoagulation
during vitrectomy for diabetic vitreous haemorrhage. Graefes Arch Clin Exp
Ophthalmol 1986;224:4237.
20 Liggett PE, Lean JS, Barlow WE, et al. Intraoperative argon endophotoco-
agulation for recurrent vitreous hemorrhage after vitrectomy for diabetic
retinopathy. Am J Ophthalmol 1987;103:1469.
21 Novak MA, Rice TA, Michels RG, et al. Vitreous haemorrhage after vitrec-
tomy for diabetic retinopathy. Ophthalmology 1984;91:14859.
22 Campbell DG, Simmons RJ, Tolentino FI, et al. Glaucoma occuring after
closed vitrectomy. Am J Ophthalmol 1977;83:639.
23 Bishop PN. Structural macromolecules and supramolecular organisation of
the vitreous gel. Progr Retinal Eye Res 2000;19:32344.
24 McLeod D, James CR. Viscodelamination at the vitreoretinal juncture in
severe diabetic eye disease. Br J Ophthalmol 1988;72:41319.
Editorials 811
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New online features at the eBJO
The BJO has now been online for over a year (which
amounts to practically eons in internet time), and perhaps
an opportunity is at hand to take stock of its internet pres-
ence. Inherent in the eBJO are capacities that diVerentiate
it from the print journal; such features as reference linking,
electronic archiving, customised alerts, and site searching,
to name a few, exploit the web to expand the functionality
of the BJO. With the recent addition of several new
features and sections, the BJOs electronic incarnation
continues to develop.
eLetters
The inauguration of eLetters brings rapid response
capabilities to the correspondence section of the BJO.
Expanding upon the Mailbox section already familiar in
the print journal, eLetters will provide an accelerated
forum for readers responses to articles and editorials. For
each article, a link allows readers to respond with eLetters
of varying lengths, to oVer comments, critiques, and ques-
tions. Submissions of eLetters are edited and selected for
posting. In turn, authors of the original article are notied
when each eLetter has been posted and encouraged to post
a reply. Any number of eLetters will be posted for a given
article, and the series of responses preserved for BJO read-
ers. By compressing the response cycle of readers
correspondence and authors reply, the eLetters feature
intends to enable a multilateral commentary not otherwise
possible in traditional formats.
Video Reports
Multimedia is another internet avenue that the paper jour-
nal simply cant follow. Video Reports, a new online
section with ophthalmological video images as its centre-
piece, is making its debut on the eBJO. Clinical and diag-
nostic images have long been indispensable to journal arti-
cles in ophthalmology. Perhaps more than any other
specialty, were positioned to utilise advances in online
video capabilities; microsurgery, for example, has awaited a
medium for full realisation in the ophthalmic literature.
Video Reports redenes what authors can communicate
in the clinical and laboratory sciences. As the rst such
feature in any journal in ophthalmology, Video Reports is
a venue for all that can best be communicated by moving
imagessurgical techniques, laboratory videos, diagnostic
technology, clinical ndings. Video Reports will feature
novel material representing advances in all areas of
ophthalmology, but also will include classic ndings
from the operating room and clinic. And some images will
stand on aesthetic merits alone, with the Video Reports
section as a sort of video gallery of beautiful or extraordi-
nary images in ophthalmology. Each video is presently lim-
ited to a few minutes, and is accompanied by a brief text
article providing background, methods, and commentary.
Video Reports accumulated from each issue will be
gathered on an ongoing basis and made available in an
online archive on the eBJO.
Data Supplements
Information capacity is another obvious advantage of the
web, one exploited by Data Supplements, a new function
of the eBJO. Data Supplements are aimed at overcoming
some traditional limitations of article size and content,
artefacts in many ways imposed by hard copy journal space
and page publication costs. To alter these, the Data
Supplements function allows authors to present electronic
material expanding upon their hard copy article. This
material can encompass extra or even complete data sets
and spreadsheets, multiple additional gures and illustra-
tions, extended elucidation on the background and discus-
sion sections, detailed methodology, and statistics. Authors
can include data in non-traditional media such as video
and audio, animated graphics and illustrations, even inter-
active content. Accessible online for every original article
in the BJO, Data Supplements oVer expanded dimensions
for authors in presenting their research, and gives readers
greater access to that research.
It has become a truism that the internet revolution is
bringing radical transformation to scientic and medical
publications, and the demise of the traditional medical
journal in the face of the web onslaught has been
pronounced for some time now. However, the facts of
readership patterns and preferences belie this, in the
biomedical elds at least. The medical journal in its basic
format fails to succumb, perhaps because the roles and
standards of medical publication have, after all, remained
the same whatever the modality employed for their
transmission. The dissemination of research, the authority
of peer review, the facilitation of literature review, and also
the simple enjoyment of readingthese interests will drive
the eBJO as it incorporates new features aVorded by
advances in internet technology. Or, to adopt Silicon
Valley parlance, the eBJO will continue to evolve killer
apps to capture eyeballs in our space.
ROBERT B BHISITKUL
Website editor, BJO
Contributors please note:
Communications from all countries except the UK and Republic of Ireland should be
sent to Professor C Hoyt, Editor, British Journal of Ophthalmology, University of California,
Department of Ophthalmology, 10 Kirkham Street, K 301, San Francisco, CA 94143-0730,
USA (tel: 001 415 502-6871; fax: 001 415 514-1512).
Manuscripts from the UK and the Republic of Ireland should be sent to Professor Andrew
Dick, UK Editor, British Journal of Ophthalmology, Division of Ophthalmology, Unversity of
Bristol, Lower Maudlin Street, Bristol BS1 2LX (tel: +44 (0)117 929-4496; fax: +44 (0)117
929-4607).
812 Editorials
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doi: 10.1136/bjo.84.8.809
2000 84: 809-810 Br J Ophthalmol

JOHN P WHITCHER and M SRINIVASAN

a new look at an old disease Leprosy

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