I appreciate Dr Van Gelder’s thoughtful comments regarding the
potential consequences of a UV+blue light absorbing intraocular lens (IOL)
on circadian rhythmicity.[1] I agree that the clinical importance of retinal
ganglion photoreceptors is currently unknown and that decreasing the
amount of blue light reaching them might affect their function.
Conversely, if photosensitive ganglia respond to circadia...
I appreciate Dr Van Gelder’s thoughtful comments regarding the
potential consequences of a UV+blue light absorbing intraocular lens (IOL)
on circadian rhythmicity.[1] I agree that the clinical importance of retinal
ganglion photoreceptors is currently unknown and that decreasing the
amount of blue light reaching them might affect their function.
Conversely, if photosensitive ganglia respond to circadian changes in
their blue light exposure rather than just the magnitude of that exposure,
a UV+blue light absorbing IOL may not impair ganglion function.
Dr Van Gelder re-emphasizes our finding that IOL chromophore
selection balances the potential loss of useful visual function against a
reduction in the risk of acute UV-blue phototoxicity. Our paper did not
state, however, that UV+blue absorbing IOLs were desirable for people with
outer retinal degeneration. Indeed, blue light is more important in
scotopic than photopic vision. Individuals with age-related macular
degeneration have greater nighttime visual problems than their peers
without it, and these scotopic problems may be exacerbated if a
significant amount of blue light is blocked by an IOL.
Reference
(1) Van Gelder RN. Blue light and the circadian clock [electronic response to Mainster MA and Sparrow JR; How much blue light should an IOL transmit?] bjophthalmol.com 2004http://bjo.bmjjournals.com/cgi/eletters/87/12/1523#257
Drs Mainster and Sparrow have provided an excellent perspective on
the relative merits and difficulties of extending IOL absorption into the
blue portion of the spectrum.[1]
However, they have not considered an unintentional consequence of
blockage of the blue portion of the spectrum: reducing the activity of
intrinsically photosensitive retinal ganglion cells.[2, 3] These cells
subserve se...
Drs Mainster and Sparrow have provided an excellent perspective on
the relative merits and difficulties of extending IOL absorption into the
blue portion of the spectrum.[1]
However, they have not considered an unintentional consequence of
blockage of the blue portion of the spectrum: reducing the activity of
intrinsically photosensitive retinal ganglion cells.[2, 3] These cells
subserve several non-visual ocular photoreceptive tasks, most prominently
the entrainment of the circadian clock to external light-dark cycles.[4]
Pupillary light responses in mice are also at least partially controlled
by this system, which appears to use a novel opsin (melanopsin) [5,6] and
possibly also a flavoprotein (cryptochrome) [7,8] as photopigments.
Experiments in mice have suggested that the action spectrum for these
photopigments peak in the blue, at approximately 480 nm, but with
substantial sensitivity to blue light to 430 nm.[9] This system appears
to be functional in humans as documented by the action spectrum for light
suppression of the pineal hormone, melatonin.[10,11]
The clinical importance of these photoreceptors is presently unknown,
although it appears that loss of retinal ganglion cells predisposes
children and young adults to disorders of sleep timing that outer retinal
disease does not.[12] While, as the authors note, there may be
substantial benefit in blocking blue-light phototoxicity, particularly for
patients with pre-existing outer retinal degeneration, these IOLS lenses
may have unintended consequences with respect to the timing of sleep and
wakefulness or levels of certain neuro-hormones.
References
1. Mainster MA, Sparrow JR. How much blue light should an IOL
transmit? Br. J. Ophthalmol. 2003;87:1523-9.
3. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion
cells that set the circadian clock. Science. 2002;295:1070-3.
4. Freedman MS, Lucas RJ, Soni B, et al. Regulation of mammalian
circadian behavior by non-rod, non-cone, ocular photoreceptors Science.
1999;284:502-4.
5. Panda S, Provencio I, Tu DC, et al. Melanopsin is required for non
-image-forming photic responses in blind mice. Science. 2003;301:525-7.
6. Hattar S, Lucas RJ, Mrosovsky N, et al. Melanopsin and rod-cone
photoreceptive systems account for all major accessory visual functions in
mice. Nature. 2003;424:75-81.
7. Van Gelder RN, Wee R, Lee JA, Tu DC. Reduced pupillary light
responses in mice lacking cryptochromes. Science. 2003;299:222.
8. Selby CP, Thompson C, Schmitz TM, Van Gelder RN, Sancar A.
Functional redundancy of cryptochromes and classical photoreceptors for
nonvisual ocular photoreception in mice. Proc. Natl. Acad. Sci. U. S. A.
2000;97:14697-702.
9. Lucas RJ, Douglas RH, Foster RG. Characterization of an ocular
photopigment capable of driving pupillary constriction in mice. Nat.
Neurosci. 2001;4:621-6.
10. Brainard GC, Hanifin JP, Greeson JM, et al. Action spectrum for
melatonin regulation in humans: evidence for a novel circadian
photoreceptor. J. Neurosci. 2001;21:6405-12.
11. Thapan K, Arendt J, Skene DJ. An action spectrum for melatonin
suppression: evidence for a novel non-rod, non-cone photoreceptor system
in humans. J. Physiol. (Lond). 2001;535:261-7.
12. Wee R, Van Gelder RN. Sleep disturbances in young subjects
with visual dysfunction. Ophthalmology. In press.
The authors report on LASIK surgery in five children with unilateral
high myopia who were presumed to have amblyopia. One subject had
bilateral high myopia.
Optic nerve hypoplasia is associated with high myopia. In addition,
anisometropic myopia is a common sequela of retinopathy of prematurity.
Thinning of the sclera with posterior staphyloma formation has long been
known to be associa...
The authors report on LASIK surgery in five children with unilateral
high myopia who were presumed to have amblyopia. One subject had
bilateral high myopia.
Optic nerve hypoplasia is associated with high myopia. In addition,
anisometropic myopia is a common sequela of retinopathy of prematurity.
Thinning of the sclera with posterior staphyloma formation has long been
known to be associated with high myopia. Best corrected visual acuity in
these patients is often limited by associated retinal and scleral
pathology.
None of the treated eyes obtained acuity better than 6/15. This
limited outcome following refractive surgery may only be due to optical
enlargement of the retinal image rather than enhanced neurosensory
function. In the 3 children who were less than 3 years old improved
literacy, familiarity with the test procedure, and the Hawthorn Effect,
were certainly important factors in their assumed improvement. The
absolute lack of progress in one child was a likely manifestation of pre-
existing retinal pathology rather than non-compliance with patching.
The authors advocate increased use of LASIK to thin the corneas of
highly myopic children who already have profound reductions in scleral
thickness. “From a clinical viewpoint, optic nerve hypoplasia should be
carefully looked for in all patients with unilateral bilateral high myopia
and visual loss.”[1] It may well be more appropriate to improve the quality
of retinal and optic nerve evaluations prior to performing irreversible
surgical procedures with unknown long term consequences for these abnormal
eyes.
References
(1) M O’Keefe and L Nolan
LASIK surgery in children
Br J Ophthalmol 2004; 88: 19-21.
(2)
Avery H. Weiss and Eric A. ROS Axial myopia in eyes with optic nerve
hypoplasia Graefe's Arch Clin Exp Ophthalmol (1992) 230:372-377
(3) McBrien NA, Gentle A. Role of the sclera in the development and
pathological complication of myopia. Progress in Retinal and Eye Research
22 (2003):307-338
(4) Wickstrom G, Bendix T. "Hawthorne effect"--what did the original
Hawthorne studies actually show? Scand J Work Environ Health. 2000
Aug;26(4):363-7
(5) Lied TR, Kazandjian VA.A Hawthorne strategy: implications for
performance measurement and improvement. Clin Perform Qual Health Care.
1998 Oct-Dec;6(4):201-4.
I am the surgeon who found the case in the Skarf article in 1983. The
patient was comatose with an acute subdural hematoma and we only found it
with the help of visual evoked responses. Our case had ipsilateral
blindness. We did not have MRI and our patient died. The very late onset
of contralateral blindness in your case gives me pause as to the actual
etiology of visual loss. One might incriminate a "do...
I am the surgeon who found the case in the Skarf article in 1983. The
patient was comatose with an acute subdural hematoma and we only found it
with the help of visual evoked responses. Our case had ipsilateral
blindness. We did not have MRI and our patient died. The very late onset
of contralateral blindness in your case gives me pause as to the actual
etiology of visual loss. One might incriminate a "double" injury with
recurrent SDH on the premise that the cumulative effect is not 10+10 but
rather 10x10. I am unaware of the plausibility of this mechanism as
perhaps there was another distinct cause of injury. Let us hope this
phenomenon remains rare, even if it is fascinating, enigmatic and stygian
all at the same time. Thank you for sharing this case; now I think I
understand less about the certainty of the genesis of this oddity.
I was delighted to read Dr Okada’s reply to my letter.[1] At the risk of
transgressing from the point of the original article [2] that dealt with a
novel technique to administer triamcinolone to a wide group of patients
with uveitis, I would like to reply:
1. The WHO guidelines are indeed silent on the treatment of latent
tuberculosis which can be defined as merely positive mantoux tests w...
I was delighted to read Dr Okada’s reply to my letter.[1] At the risk of
transgressing from the point of the original article [2] that dealt with a
novel technique to administer triamcinolone to a wide group of patients
with uveitis, I would like to reply:
1. The WHO guidelines are indeed silent on the treatment of latent
tuberculosis which can be defined as merely positive mantoux tests with no
clinical, microbiological, or radiographic evidence of active tuberculosis
(TB).[3] These patients may be treated with single or two drug therapy to
prevent progression to active TB [4] but patients with an active uveitis
would not fall within this definition and probably should be treated as
patients with active extrapulmonary TB irrespective of the detection or
otherwise of an infective focus. The absence of a detectable focus of
systemic TB (usually pulmonary) should not lead to a diagnosis of latent
tuberculosis.
In patients suspected of ocular TB, the findings of systemic TB especially
in those patients with infective manifestations (like choroidal tubercles)
, suggests the need to receive the full four drug regime but considerable
latitude exists in those patients in whom there is neither a detectable
systemic focus or microbiologic evidence. As ocular TB has been known to
occur even in the absence of systemic foci,[5] it may be prudent to
advise a full four drug course rather than one/ two drug regimes.
Inadequate regimes would lead to the development of microbial resistance
and subsequent therapeutic difficulties.
2. The authors theorize that certain cases may be due to an immune
reaction to
sequestered mycobacterial antigen. Recent mouse models have demonstrated
an initial pulmonary infection followed by the appearance of bacteria at
the draining lymph nodes, at which stage a T cell immune response is
generated.[6] Does this response lead to the release of antigen into the
bloodstream leading to the sequence of events we describe as ocular TB? A
mantoux test would probably be positive in these patients indicating
recent infection (but not necessarily active disease) but whether they
would need antitubercular (as opposed to only immunosuppressive agents)
drugs remains unknown.
References
1. Okada AA and Wakabayashi T. Trans-Tenon's retrobulbar triamcinolone infusions in uveitis [electronic response to Okada et al. Trans-Tenon’s retrobulbar triamcinolone infusion for the treatment of uveitis] http://bjo.bmjjournals.com/cgi/eletters/87/8/968#210
2. AA Okada, T Wakabayashi, Y Morimura, S Kawahara, E Kojima, Y Asano
and T Hida. Trans-Tenon’s retrobulbar triamcinolone infusion for the
treatment of uveitis. Br J Ophthalmol 2003; 87:968-971.
3. American Thoracic Society. Diagnostic Standards and Classification of
Tuberculosis in Adults and Children. Am. J. Respir. Crit. Care Med 2000;
161(4): 1376-1395.
4. Small PM. Fujiwara PI. Management of Tuberculosis in the United States.
N Engl J Med. 2001; 345:189-200.
5. Sarvananthan N, Wiselka M, Bibby K. Intraocular tuberculosis without
detectable systemic infection. Arch Ophthalmol. 1998;116(10):1386-8.
6. Chackerian AA, Alt JM, Perera TV, Dascher CC, Behar SM. Dissemination
of Mycobacterium tuberculosis Is Influenced by Host Factors and
Precedes the Initiation of T-Cell Immunity. Infection and Immunity.2002,
70(8): 4501-4509.
I read with great interest the article by Isenberg et al.[1] on "A
double
application approach to ophthalmia neonatorum prophylaxis." The authors
deserve to be commended for their pioneering interest in childhood
blindness. There are certain points that I would like to clarify and
supplement with regard to their study.
1. The authors have mentioned that only babies born by a vagin...
I read with great interest the article by Isenberg et al.[1] on "A
double
application approach to ophthalmia neonatorum prophylaxis." The authors
deserve to be commended for their pioneering interest in childhood
blindness. There are certain points that I would like to clarify and
supplement with regard to their study.
1. The authors have mentioned that only babies born by a vaginal
delivery
were studied, since the eyes of babies delivered by caesarean section
were
previously proved to be nearly always sterile. This would result in a
gross underestimation of the incidence of ophthalmia neonatorum in this
study, for the following reason.
By convention, ophthalmia neonatorum is defined as conjunctivitis
arising within one month after birth.2 Hence, some of these conjunctival
infections could originate from sources other than the maternal vaginal
and cervical flora. In fact, some cases of ophthalmia neonatorum
especially those caused by Staphylococcus aureus could have originated
at
home, as previously reported by the authors themselves.2 In the same
study, no significant difference in the frequency or type of infection
was
seen among the infants delivered vaginally or by caesarean section.[2]
Other authors, too have made similar observations. Krohn et al.[3]
have
found some cases of ophthalmia neonatorum to have been acquired from the
infants' nasopharyngeal passages or from their care givers after birth.
Verma et al.[4] in a prospective study from India, found no correlation
between the microbiology of the conjunctival swabs of the infected eyes
(Staphylococcus aureus was the commonest isolate) and the vaginal and
cervical swabs of the mothers (Escherichia coli was the commonest
isolate). They concluded that most of the cases of ophthalmia neonatorum
were acquired postnatally.
In the light of these previously reported studies, I feel that exclusion
of cases that were delivered by caesarean section was not warranted and
weakens the power of this study. The efficacy of the second drop of
povidone iodine was not tested on a significant proportion of the cases
of
ophthalmia neonatorum (those cases affecting the babies delivered by
caesarean section).
2. It would be relevant to note the percentage of ophthalmia
neonatorum
cases with neonatal dacryocystitis due to congenital nasolacrimal duct
obstruction in this series. Such cases obviously would not have
benefited
from a second drop of povidone-iodine.
3. The Indian study by Verma et al. l4 found a seasonal incidence to
ophthalmia neonatorum with two peaks: in the February and May-June, in
most probability due to the monsoon and the hot tropical climate with
the
attendant eye seeking flies. It would be interesting to know whether any
such seasonal variation was noted in this study that was carried out in
Kenya, a country with a hot tropical climate, like India. If so, the
efficacy of the second drop could be investigated again during such
peaks.
Vasumathy Vedantham MS, DNB, FRCS
Retina - Vitreous Service, Aravind Eye hospital and Postgraduate
Institute
of Ophthalmology
1, Anna Nagar, Madurai - 625 020, Tamilnadu, India.
Telephone: 0452-2532653
Fax: 0452-2530984
Email: drvasumathy@yahoo.com
References
1. Isenberg SJ, Apt L, Signore M Del, Gichuhi S, Berman NG. A double application approach to ophthalmia neonatorum prophylaxis. Br J Ophthalmol 2003;87(12): 1449-1452.
2. Isenberg SJ, Apt L,Wood M. A controlled trial of povidone-iodine as prophylaxis against ophthalmia neonatorum. N Engl J Med 1995;332:562-6.
3. Krohn MA, Hillier SL, Bell TA, Kronmal RA, Grayson JT. The bacterial etiology of conjunctivitis in early infancy. Am J Epidemiol 1993;138:326-32.
4. Verma M, Chhatwal J, Vareghese PV. Neonatal conjunctivitis: a
profile.
Indian Pediatr 1994;31(11): 1357-61.
We thank Dr Doft, et al. for their useful and expert opinion. The
choice of which agent to use to empirically treat gram-negative organisms
implicated in endophthalmitis remains controversial. As amikacin has been
proven to cause macular infarction, we feel one should look at viable
alternatives.
Ceftazidime is already in widespread use in the UK and appears not only to
have an excellent safe...
We thank Dr Doft, et al. for their useful and expert opinion. The
choice of which agent to use to empirically treat gram-negative organisms
implicated in endophthalmitis remains controversial. As amikacin has been
proven to cause macular infarction, we feel one should look at viable
alternatives.
Ceftazidime is already in widespread use in the UK and appears not only to
have an excellent safety profile but also good clinical effect.
Unfortunately until we have proper in vivo and in vitro “head-to-head”
comparison studies, it is difficult to know which is the more efficacious
agent. As far as synergism is concerned, vancomycin and ceftazidime are
usually not tested together because vancomycin acts on gram-positive
organisms and ceftazidime is used primarily for gram-negative infections.
However, there is however one study that reported synergy between
vancomycin and ceftazidime against gram-positive organisms.[1]
The study by Kwok and colleagues raises a concern that ceftazidime
precipitation, as assessed by in-vitro studies, may affect its action in
vivo.[2] The authors of our study have noticed temporary precipitants in
vivo without apparent alteration of clinical effect. (AR)
Previous animal models do show that ceftazidime reaches intravitreal
minimal inhibitory concentrations for common gram-negative microbes after
a single intravitreal injection.3 Perhaps assay at the time of repeat
injection, non-invasive confocal Raman spectroscopy of the anterior
chamber, or further animal models may provide additional insight into
ceftazidime pharmacokinetics and the phenomenon of ceftazidime
precipitation so as to guide future therapeutic choice.
Ultimately the decision lies with the treating surgeon who should be aware
of both the efficacy and safety profiles of the agents available. We still
believe, with the evidence presented in our article, that ceftazidime
currently represents the best agent for the treatment of gram-negative
microbes in endophthalmitis.
References
1. Simon C, Littschwager G. In vitro activity of ceftazidime in
combination with other antibiotics. Infection. 1985 Jul-Aug;13(4):184-9.
2. Kwok AK, Hui M, Pang CP, et al. An in vitro study of ceftazidime
and vancomycin concentrations in various fluid media: implications for use
in treating endophthalmitis. Invest Ophthalmol Vis Sci. 2002
Apr;43(4):1182-8.
3. Mochizuki K, Yamashita Y, Torisaki M, et al. Intraocular kinetics
of ceftazidime (Modacin). Ophthalmic Res. 1992;24(3):150-4.
We read with interest the article by Joussen et al. on the long term
results of retinectomy for the treatment of intractable glaucoma.[1] We
congratulate the authors for studying this innovative method for the
management of refractory glaucoma with a long follow-up of five years.
The high incidence of complications in the study however has aroused
our concerns as only 15.9% of patients...
We read with interest the article by Joussen et al. on the long term
results of retinectomy for the treatment of intractable glaucoma.[1] We
congratulate the authors for studying this innovative method for the
management of refractory glaucoma with a long follow-up of five years.
The high incidence of complications in the study however has aroused
our concerns as only 15.9% of patients completed the study uneventfully.
Further vitreoretinal surgeries were required in 47.7% due to retinal
complications. Moreover, the incidence of hypotony, phthisis and
enucleation was 25%, 20% and 16% respectively and these figures are higher
compared with other treatment modalities like glaucoma implants and
cyclodiode. We have previously studied the use of Ahmed valve implant for
complicated glaucoma, and hypotony, phthisis and enucleation occurred in
10.8%, 3.1% and 1.5% respectively.[2] A recent study on the management of
refractory glaucoma by cyclodiode similarly found a lower rate of hypotony
and phthisis of 9.5% and 5.3% respectively.[3] The high complication
rates in the study by Joussen et al. may be due to the negative case
selection with high incidence of aphakic (30%) and infantile and juvenile
glaucoma (7%). Further controlled study comparing retinectomy with other
treatment modalities may therefore be warranted.
In this evidence-based era, emphasis should be placed on outcomes
which are "patient-oriented evidence that matters" (POEMs).[4] It was
stated by the authors that the main intentions of the surgery were to
relieve pain and to preserve the eye without discomfort. Unfortunately,
these POEMs were not included in the final outcome measures. Instead,
success was determined by "disease-oriented evidences" (DOEs) like
intraocular pressure and retinal attachment which are surrogate
outcomes.[5] These DOEs may not correlate well with the
patients' symptoms and it would be valuable if the authors can include the
level of pain and discomfort as other outcome measures for the study.
References
1. Joussen AM, Walter P, Jonescu-Cuypers CP, et al. Retinectomy for
treatment of intractable glaucoma: long term results. Br J Ophthalmol
2003;87:1094-1103.
2. Lai JS, Poon AS, Chua JK, et al. Efficacy and safety of the Ahmed
glaucoma valve implant in Chinese eyes with complicated glaucoma. Br J
Ophthalmol 2000;84:718-21.
3. Murphy CC, Burnett CA, Spry PG, et al. A two centre study of the dose-
response relation for transscleral diode laser cyclophotocoagulation in
refractory glaucoma. Br J Ophthalmol 2003;87:1252-7.
4. Shaughnessy AF, Slawson DC, Bennett JH. Becoming an information
master: a guidebook to the medical information jungle. J Fam Pract
1994;39:489-99.
5. Temple R. Are surrogate markers adequate to assess cardiovascular
disease drugs? JAMA 1999;282:790-5.
Dear Editor
I appreciate Dr Van Gelder’s thoughtful comments regarding the potential consequences of a UV+blue light absorbing intraocular lens (IOL) on circadian rhythmicity.[1] I agree that the clinical importance of retinal ganglion photoreceptors is currently unknown and that decreasing the amount of blue light reaching them might affect their function. Conversely, if photosensitive ganglia respond to circadia...
Dear Editor
Drs Mainster and Sparrow have provided an excellent perspective on the relative merits and difficulties of extending IOL absorption into the blue portion of the spectrum.[1]
However, they have not considered an unintentional consequence of blockage of the blue portion of the spectrum: reducing the activity of intrinsically photosensitive retinal ganglion cells.[2, 3] These cells subserve se...
Dear Editor
The authors report on LASIK surgery in five children with unilateral high myopia who were presumed to have amblyopia. One subject had bilateral high myopia.
Optic nerve hypoplasia is associated with high myopia. In addition, anisometropic myopia is a common sequela of retinopathy of prematurity. Thinning of the sclera with posterior staphyloma formation has long been known to be associa...
Dear Editor
I am the surgeon who found the case in the Skarf article in 1983. The patient was comatose with an acute subdural hematoma and we only found it with the help of visual evoked responses. Our case had ipsilateral blindness. We did not have MRI and our patient died. The very late onset of contralateral blindness in your case gives me pause as to the actual etiology of visual loss. One might incriminate a "do...
Dear Editor
I was delighted to read Dr Okada’s reply to my letter.[1] At the risk of transgressing from the point of the original article [2] that dealt with a novel technique to administer triamcinolone to a wide group of patients with uveitis, I would like to reply:
1. The WHO guidelines are indeed silent on the treatment of latent tuberculosis which can be defined as merely positive mantoux tests w...
Dear Editor
I read with great interest the article by Isenberg et al.[1] on "A double application approach to ophthalmia neonatorum prophylaxis." The authors deserve to be commended for their pioneering interest in childhood blindness. There are certain points that I would like to clarify and supplement with regard to their study.
1. The authors have mentioned that only babies born by a vagin...
Dear Editor
We thank Dr Doft, et al. for their useful and expert opinion. The choice of which agent to use to empirically treat gram-negative organisms implicated in endophthalmitis remains controversial. As amikacin has been proven to cause macular infarction, we feel one should look at viable alternatives. Ceftazidime is already in widespread use in the UK and appears not only to have an excellent safe...
Dear Editor
We read with interest the article by Joussen et al. on the long term results of retinectomy for the treatment of intractable glaucoma.[1] We congratulate the authors for studying this innovative method for the management of refractory glaucoma with a long follow-up of five years.
The high incidence of complications in the study however has aroused our concerns as only 15.9% of patients...
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