In reply to the comments of Stodtmeister and colleagues [1] on our recent paper [2], we won´t argue the correlation between central corneal thickness (CCT) and intraocular pressure (IOP), but we mistrust the clinical application of correcting factors. Stodtmeister et al compare our study to that of Ehlers et al [3] which is often cited to prove an influence of corneal thickness on applanatory measurement.
In reply to the comments of Stodtmeister and colleagues [1] on our recent paper [2], we won´t argue the correlation between central corneal thickness (CCT) and intraocular pressure (IOP), but we mistrust the clinical application of correcting factors. Stodtmeister et al compare our study to that of Ehlers et al [3] which is often cited to prove an influence of corneal thickness on applanatory measurement.
In our paper simultaneous IOP measurement by applanation and by intracameral tonometry was performed. Assuming a normal CCT of 520mm, an IOP correction for every 10mm-change in corneal thickness is recommended. But in the Ehlers paper, there are some confusing arguments:
1. Ehlers et al [3] describe a very good correlation between direct and intracameral IOP measurement (correlation coefficient approximated 1). Unfortunately, they didn´t give the measured IOP values. In figure 2, the slopes of correlation lines at different CCT are presented for rabbits (not for human eyes!). The increase of the slopes are less than 45°. With the paper of Bland and Altman [4] 1 in mind, a minor methodological agreement is very likely. It is therefore not allowed to recalculate the values P10 and P30 (applanatory versus intracamerally IOP, measured at an adjusted IOP of 10 and 30 mmHg) for a relevant IOP level of 20 mmHg (P20). It is indeed very interesting that the group didn´t measure at an IOP level of 20 mmHg.
2. The equipment for intracameral measurement is comparable to our device. We also calibrated the transducer before each measurement. When we tested our device on enucleated human eyes in a preclinical study, a very sensitive change of IOP values was noted when touching the eyeball. We therefore decided not to measure the IOP simultaneously. We also confirmed these findings in vivo. For these reasons, we expected an unpredictable increase of applanatory measurement during intracamerally IOP in the study of Ehlers [3]. Unfortunately, there is no comment about this problem.
Stodtmeister pointed out the `pitfalls in pressure measurement´ (bubbles or tiny particles) without mentioning that Ehlers had not solved these problems in his trial on human eyes. We are also missing any information about the canula size. Additionally the used device ressembles an `open system´ where fluid could circulate through the anterior chamber and trabecular meshwork. This can generate an noticeable change in intraocular pressure.
3. Ehlers et al [3] measured IOP in patients with an acute eye disease (glaucoma patients requiring surgery) and cataract patients. He changed the IOP to 10 and 30 mmHg. This method is questionable especially in glaucoma patients, because an acute IOP change could also entail endothelial alterations which could alter CCT. Unfortunately, he didn´t measure the CCT after IOP changing. We have no information about the influence of IOP alterations on CCT.
In summary, the above mentioned study gives a hint on the influence of CCT on IOP measurement, but does not prove this assumption. It is amazing, that within the last 25 years nearly 50 published papers refer to the Ehlers study [3] without checking the results by intracameral measurement themselves.
All papers measuring CCT and applanatory IOP renouncing intracameral measurement described an increasing IOP with inreasing CCT. We could also confirm this finding in our study (y= 14.5 + 8.4 ´ CCT, where y is applanatory IOP in mmHg). Of course, it would be easiest to claim the cornea for this correlation. But it is also conceivable that eyes with thick corneas (e.g. OHT) have reduced ocular outflow facility and consequently elevated IOP, for instance due to a `thick´ trabecular meshwork.
With the present study [2] we tried to find out if the above recommended correcting factors are clinically applicable or not. According to our findings they are not. We found quite variable and unpredictable differences between intraocular pressure and applanatory measurement in an individual patient. Interestingly, the same results can be found in the Ehlers study [3]. Therefore, we renew our warning to recalculate the IOP depending on central corneal thickness.
References
(1) Stodtmeister R, Kron M, Gaus W. IOP measurement and central corneal thickness. Brit J Ophthalmol 2001 (eLetter).
(2) Feltgen N, Leifert D, Funk J. Correlation between central corneal thickness, applanation tonometry, and direct intracameral IOP readings. Brit J Ophthalmol 2001; 85:85-87.
(3) Ehlers N, Bramson T, Sperling S. Applanation tonometry and central corneal thickness. Acta Ophthalmol 1975; 53:34-43.
(4) Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1:307-10.
[Please note that the tables for this letter will be available in the December issue of BJO.]
In the recent paper by Feltgen et al [1], the intraocular pressure was measured by Goldmann applanation tonometry and by using a cannula inserted into the anterior chamber connected with a pressure transducer. Thus the measurement took place omitting a possible influence of the cornea on the result. Marx et al[...
[Please note that the tables for this letter will be available in the December issue of BJO.]
In the recent paper by Feltgen et al [1], the intraocular pressure was measured by Goldmann applanation tonometry and by using a cannula inserted into the anterior chamber connected with a pressure transducer. Thus the measurement took place omitting a possible influence of the cornea on the result. Marx et al[2] believed that by intracameral measurement the "true" intraocular pressure may be measured.
Feltgen et al share his opinion. They believe, therefore, that they have compared the intraocular pressure measured with and without the possible influence of the cornea.
Feltgen et al write in their conclusion: "There is no systematic error of applanation tonometry with increasing central corneal thickness (CCT). Therefore it is inadequate to recalculate IOP based on regression formula of applanatory IOP versus CCT." They base their conclusion on their results. In our opinion their papers shows the following methodological deficits:
1. both methods used for measuring IOP are not up to the demands of the scientific technique of measurement;
2. their intracamerally measured IOP values do not reflect the true IOP due to bias;
3. a non-significant regression coefficient does not prove that the slope is actually 0 and therefore, by a non-significant regression coefficient it is not proven that applanatory readings are not influenced CCT;
4. the goodness of fit of the linear regression model is insufficient; and
5. an important covariate (true IOP value) was omitted in the linear regression. We would like to discuss these points in detail.
In Feltgen et al's study the only criterion for the quality of measurement is the stability of the readings on the monitor. However, it is not sufficient to conclude from the presence of stability that the scale readings represent the "true" pressure value which is at the tip of the cannula. If there were a barrier inside the cannula the reading on the monitor would also be stable but would not represent the pressure at the tip. There are many pitfalls in pressure measurements by thin pipes that we know from my own studies[3,4]. Minute air bubbles or tiny particles influence the result a great deal. If we want to know that a display reading represents the quantity in question then we have to guarantee that the measurement system has the opportunity to react freely to changes of the quantity. This guarantee can be obtained by feeding a known signal to the input of the system and by observing the output. If the output reacts in the expected way then the guarantee is given. Ehlers et al [5] have realized this demand in their rabbit experiments and we in electrophysiology[6-9]. As long as this demand is not met the results are not definite, give cause for criticism and lead to misinterpretations.
Feltgen et al write in their paper ". . . however, we believe intracamerally measured IOP values reflect the 'true' IOP more accurately." Scientific facts should not be a matter of belief. The belief of the authors in the values they measured is not justified. In the study under discussion, figure 2 shows the scatterplot of the pressure differences versus central corneal thickness. From this diagram and from their statistical calculations the authors draw their conclusions. Their results are quite different from those of Ehlers et al [5] shown in figure 4 of their paper. Thus we must compare these two data sets. To facilitate this task, we have digitized the data presented in the figures of Feltgen et al. and of Ehlers et al. They are shown in figures 1 and 2 on the same scale. The difference is striking.
Let us at first consider a possible reason from the physical point of view: Ehlers et al [5] reduced the pressure measurement to a basic physical quantity, here to the length of a water column. We can, therefore, trust in the results of Ehlers more than in the results of Feltgen et al. who used a pressure transducer which has a zero point fluctuation up to 4.5 mm Hg (Abbott GmbH. Data file). It is recommended also by the manufacturer that the zero point of the measurement system has to be determined for each patient by comparison with a water column (Dr. Beer, Abbott GmbH, Wiesbaden; personal communication). This procedure is not described by Feltgen et al.
Therefore, none of the methods used in the article by Feltgen et al. may be called a reference method and all methods may be prone to error and bias. Hence, analysis of differences in IOP between these models is inappropriate in order to decide on the necessity of a conversion formula.
Further, the variability of differences is large, which is probably due to errors in the intracameral measurement of IOP. Regression lines with a small non-significant slope (0.38mm Hg IOP difference per 0.1 mm cornea thickness in the article by Feltgen et al.) may occur in both situations where variability is high and also where it is low. Only, in the latter case, when - as a consequence of the small variability - the confidence interval for the slope is narrow, may this be interpreted in the way that the covariate included in the model (i.e., CCT) has no effect. If the variability is high and the slope is approximately 0, this may lead to the conclusion that IOP measurement is inappropriate due to too large error. This conclusion is allowed if no other essential covariates were overlooked. If variability is high and the slope of the regression line is near 0, a large p-value may not be interpreted as a proof of no effect of the covariate considered in the regression model. For better interpretation of the results a confidence interval for the estimated slope would have been much more appropriate than a p-value.
As a consequence, the differences between measurements from applanation tonometry and a reference method, like the intraocular hydrostatic pressure done by Ehlers et al., should be evaluated first. If measurements by applanatory IOP are highly correlated with measurements by the reference method a conversion formula may be derived from linear regression. Under the assumption of small variability of residuals (difference between observed value and regression line), i.e., a satisfactory goodness of fit (e.g. r2³60%), results may lead to the recommendation of the usage of a conversion formula. In contrast, Feltgen et al report an r2 of 0.2%. Only for small residuals, a slope approximately 0, and a confidence interval with limits near to 0, may the recommendation that a conversion formula is not necessary be given.
Moreover, the large variability in IOP differences may occur due to the fact that Feltgen et al did not adjust for "true" intraocular hydrostatic pressure as Ehlers et al did. Since Ehlers et al. calculated separate linear regression models for 10mmHg and 30mmHg which resulted in different intercepts and slope parameters, this might be another source of variation in the IOP differences from Feltgen et al. which were unadjusted.
We hope our arguments are convincing and ask that you bring them to the attention of your readers.
Prof. Dr. med. Richard Stodtmeister
Private Practice, Ophthalmic Surgeon St. Elisabeth Hospital
Rodalben (Palatinate)
Turnstrasse 24
D-66953 Pirmasens
Dr. rer.biol.hum Martina Kron
Prof. Dr.phil. Wilhelm Gaus
University of Ulm
Department of Biometry and Medical Documentation
Schwabstrasse 13
D-89075 Ulm
References
(1) Feltgen N, Leifert D, Funk J. Correlation between central corneal thickness, applanation tonometry, and direct intracameral IOP readings. Brit J Ophthalmol 2001;85:85-87.
(2) Marx W, Madjlessi F, Reinhard T, Althaus C, Sundmacher R. [More than four years' experience with electronic intraocular needle tonometry] Mehr als vier Jahre Erfahrung mit der elektronischen intraokularen Nadel-Druckmessung bei irregularen Hornhauten. Ophthalmologe 1999;96:498-502.
(3) Stodtmeister R, Kästner R, Pillunat LE. Saugnapfmethoden. In: Straub W, Kroll P, Küchle HJ, eds. Augenärztliche Untersuchungsmethoden. Stuttgart: Ferdinand Enke, 1995; 1 edn. 436-461.
(4) Stodtmeister R, Hornberger M, et al. Okulo-Oszillo-Dynamographie nach Ulrich und Ulrich: Ergebnisse bei Augengesunden. Klin.Monatsbl.Augenheilkd. 1988;192:219-233.
(5) Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thickness. Acta Ophthalmol(Copenh) 1975;53:34-43.
(6) Stodtmeister R, Wilmanns I. Bandpass measurements in the electroretinographic electrode circuit. Albrecht.Von.Graefes.Arch.Klin.Exp.Ophthalmol. 1978;208:263-267.
(7) Stodtmeister R, Wilmanns I. Changes of the current pathways in the eye due to coating agents during electroretinography. Albrecht.Von.Graefes.Arch.Klin.Exp.Ophthalmol. 1978;208:255-260.
(8) Stodtmeister R, Wilmanns I, Koenig A, Gabriel W. EEG-Registrierung beim Hirntod. Prakt.Anaesth. 1978;13:446-449.
(9) Wilmanns I, Stodtmeister R. Ein neues Verfahren zur Kalibrierung elektrophysiologischer Untersuchungseinheiten. Albrecht.Von.Graefes.Arch.Klin.Exp.Ophthalmol. 1977;205:33-39.
The report of Mauriello et al. "Adenoid squamous carcinoma of the conjunctiva -- a clinicopathologic study of 14 cases" [1] has profoundly impressed us as plastic and reconstructive surgeons who encounter the problem of exenteration or enucleation. Facial plastic surgeons are most frequently asked to reconstruct the exenterated orbit, but also often meet the patient before surgery when the decision for exentera...
The report of Mauriello et al. "Adenoid squamous carcinoma of the conjunctiva -- a clinicopathologic study of 14 cases" [1] has profoundly impressed us as plastic and reconstructive surgeons who encounter the problem of exenteration or enucleation. Facial plastic surgeons are most frequently asked to reconstruct the exenterated orbit, but also often meet the patient before surgery when the decision for exenteration or enucleation is undertaken with the ophthalmologist. We would like to share our opinion about the surgical treatment in cases of this highly invasive carcinoma of the conjunctiva inspired by the interesting material of Mauriello et al.
Though the paper principally reveals the histopathologic features of this type of carcinoma, the authors also report the results of their surgery. They point out that the optimum treatment includes wide excision with documented histologic clear margins of resection on permanent sections and frequent follow-up; in 1997, Tessier et al [2] considered epitheliomas involving the conjunctival fornices of the eyelids indicated for orbital exenteration. Moshfeghi et al [3] point out that enucleation is indicated in cases of intraocular tumors, otherwise exenteration should be performed. In our opinion when cancer involves the conjunctiva of the corneoscleral limbus and particularly bulbar conjunctiva, like in the cases of Mauriello et al, it is very likely that the process might have involved structures outside the eye bulb, not accessible for immediate verification, since the conjunctiva is practically outside the ocular bulb. This is confirmed by Johnson et al [4] who consider the conjunctival squamous cell carcinoma (SCC, which is less invasive according to Mauriello et al) the primary reason for secondary orbital SCC.
In cases of conjunctival involvement it would probably be wise to proceed directly to orbital exenteration. It is well known that the decision to perform exenteration, enucleation or evisceration is hard to take. However, surgeries in cases like those of Mauriello et al would probably lead to partial or total loss of sight. When the surgeons are certain that sight would be totally lost, probably the wisest decision would be to perform an exenteration which will provide clear margins. Moreover, some authors proceed directly to orbital exenteration even in cases of benign but aggressive tumors [5]. In our practice we had a case of SCC of the skin of the nasolabial fold involving the lower eyelid and conjunctiva. Tumor excision and hemirhinectomy was completed with orbital exenteration. Eight months later there was a recurrence of the part of the nose left after the primary operation but not in the orbit, which is free of recurrence after 12 months.
Perhaps, to ensure the life of the patient with conjunctival carcinoma, one should proceed to the larger surgical intervention, moreover the up-to-date achievements of plastic surgery provide options for successful reconstruction of the exenterated orbit.
C Shipkov and Y Anastassov
Plastic and Craniofacial Ward
Department of Pediatric Surgery
Higher Medical Institute
Plovdiv
Bulgaria
References
(1) Mauriello JA, Abdelsalan A, McLean, IW. Adenoid squamous carcinoma of the conjunctiva - a clinicopathologic study of 14 cases. Br J Ophthalmol 1997;81;1001-1005.
(2) Rougier J, Tessier P, Hervouet F, et al. L'extenteration de l'orbite. In: Chirurgie plastique orbito-palpebrale. 3d ed. Masson: Paris, 1997:33-43.
(3) Moshfeghi DM, Moshfeghi AA, Finger PT. Enucleation. Survey of Ophthalmol 2000;44;277-301.
(4) Johnson TE, Tabarra KF, Weatherhead RG, et al. Secondary squamous cell carcinoma of the orbit. Arch Ophthalmol 1997;115:75-78.
(5) Morand B, Bettega G, Bland G, et al. Oncocytoma of the eyelid: an aggressive benign tumor. Ophthalmology 1998;105:2220-24.
We read with interest the excellent article by Shah et al. [1] The authors compared the outcomes of epithelial debridement for photorefractive keratectomy (PRK) with those of epithelial flap for PRK. They used 20% ethanol for 30 seconds and 45 seconds for the debridement and flap techniques, respectively. They observed that epithelial flap resulted in faster visual rehabilitation and reduced haze. We have ob...
We read with interest the excellent article by Shah et al. [1] The authors compared the outcomes of epithelial debridement for photorefractive keratectomy (PRK) with those of epithelial flap for PRK. They used 20% ethanol for 30 seconds and 45 seconds for the debridement and flap techniques, respectively. They observed that epithelial flap resulted in faster visual rehabilitation and reduced haze. We have observed that laser subepithelial keratomileusis (LASEK), using hinged epithelial flap reduced the incidence of postoperative pain and of corneal haze as compared to PRK.[2,4]
In the study by Shah et al1 20% dilute alcohol was applied for 45 seconds for epithelial flap-treated eyes. The duration of exposure may have facilitated epithelial flap removal in this study. Gabler et al [3] have reported that the vitality of corneal epithelial cells was reduced when exposure to 20% alcohol exceeded 45 seconds. We employed the same alcohol concentration to treat our patients using a similar surgical LASEK technique4 as well as using the Camellin LASEK technique.[2] However, we used a shorter duration 20 to 30 seconds and we did not encounter any difficulty in the creation of LASEK epithelial flaps. It was our impression that decreased exposure to alcohol would result in increased epithelial flap viability, which may be associated with less postoperative pain and tearing. We have had limited experience of applying the same alcohol concentration for 45 seconds in LASEK procedure, which allowed greater ease of lifting of the epithelial flap without tears or buttonholes, but the flap did not seem to have good adherence. The data reported by Shah et al1 suggests that our assumptions regarding the need for reduced exposure times to alcohol may have been wrong.
Based on the convincing data by Shah et al,[1] we plan to modify our technique and increase the duration of alcohol to 45 seconds. Before changing our technique, however, we would appreciate any caveats regarding the authors' technique, which may minimize potential problems.
We have used a therapeutic contact lens in the first 3-4 days after surgery. In the study by Shah et al1 PRK was performed in one eye and epithelial hinge flap procedure in the other eye, without using a contact lens. Our patients received therapeutic soft contact lenses after surgery to minimize postoperative pain. In the discussion of their results, Shah et al1 have indicated that they have started using contact lenses in subsequent patient treatments. We would appreciate the authors' recommendations regarding optimal alcohol exposure in setup of contact lens use and their experience with the effect of contact lens use on pain reduction after 45 seconds of alcohol exposure.
Jae Bum Lee
Dimitri T. Azar
Department of Ophthalmology
Massachusetts Eye and Ear Infirmary
References
(1) Shah S, Saran ARS, Doyle SJ, et al. The epithelial flap for photorefractive keratectomy. Br J Ophthalmol 2001;85;393-6.
(2) Lee JB, Seong GJ, Lee JH, et al. Comparison of laser epithelial keratomileusis and photorefractive keratectomy for low to moderate myopia. J Cataract Refract Surg 2001;27:565-70.
(3) Gabler B, Mohrenfels WV, Lohmann CP. Laser epithelial keratomileusis (LASEK): A histological study to investigate the vitality of corneal cells after alcohol exposure. Invest Ophthalmol Vis Sci 2001;42;S600.
(4) Azar DT, Ang RT, Lee JB, et al. Laser subepithelial keratomileusis (LASEK): Electron microscopy and visual outcomes of flap PRK. Curr Opin Ophthalmol 2001 Aug; in press.
We were excited to see the recent case report of Park et al regarding the 30 year old man with horizontal locked-in syndrome and disconjugate gaze.[1] We were intrigued by the description of his eye movements on attempted horizontal gaze, whereas "when the patient was asked to look to the right side, the right eye moved upward with intorsion, and at the same time, left eye moved downward and extorsion ... when...
We were excited to see the recent case report of Park et al regarding the 30 year old man with horizontal locked-in syndrome and disconjugate gaze.[1] We were intrigued by the description of his eye movements on attempted horizontal gaze, whereas "when the patient was asked to look to the right side, the right eye moved upward with intorsion, and at the same time, left eye moved downward and extorsion ... when the patient was asked to look to the left side, ... the left eye moved upward with intorsion whereas the right eye moved downward with extorsion." MR imaging revealed a large ventral pontine infarct. The authors postulated that the lesion caused a disturbance in the neural integration of prenuclear inputs to the interstitial nucleus of Cajal.
We believe we can refine further their mechanism for this observed disconjugate gaze based on the anatomy of the vestibular ocular reflect pathways, as it is likely a type of bilateral skew deviation. Each semicircular canal provides excitatory innervation to an extraocular muscle and its contralateral yoke, and inhibitory innervation to the corresponding antagonist extraocular muscles.[2] The otolithic pathways are less well understood but are believed to follow the same pathways as the semicircular canal pathways.[3] Each anterior semicircular canal provides excitatory innervation to the ipsilateral superior rectus and the contralateral inferior oblique muscle, while inhibiting the yoke ipsilateral inferior rectus and contralateral superior oblique muscle. Unilateral injury to these vestibular-ocular pathways produces classic skew deviation with hypertropia of one eye in all fields of gaze, whereas bilateral injury produces alternating hypertropia in side gaze. Bilateral damage to anterior canal pathways causes a posterior canal predominance with bilateral tonic downgaze.[4]
Theoretically, bilateral damage to the otolithic-ocular pathways corresponding to those of the anterior semicircular canal should produce the motility disturbance described in the patient reported by Park et al. The disinhibition resulting from such damage would produce posterior canal predominance, and increase tonus to all four depressors (both inferior recti, and both superior obliques). Since the vertical action of the superior oblique is more prominent in adduction, the abducting eye should have a relative hypertropia on side gaze (alternating skew on lateral gaze). Likewise, because the torsional action of the superior oblique is more prominent in abduction, dynamic intorsional movements of the hypertropic eye would be seen on attempted abduction.
In this scenario, fundus examination should demonstrate bilateral intorsion in primary position, and detailed motility measurements would show an A-pattern. However, these findings would have been difficult to detect in this patient who could not elevate the eyes above the midline. We believe that bilateral injury to the same pathways may be responsible for A-pattern strabismus and bilateral superior oblique overaction seen in some patients with posterior fossa disease.[5]
Sean P. Donahue
Associate Professor of Ophthalmology, Pediatrics and Neurology
Vanderbilt University School of Medicine
Michael C. Brodsky
Department of Ophthalmology
University of Arkansas for Medical Science
References
(1) Park SH, Na DL, Kim M. Disconjugate vertical ocular movement in a patient with locked-in syndrome. Br J Ophthalmol 2001;85:496.
(2) Zee DS. The organization of the brainstem ocular motor subnuclei. Ann Neurol 1978;4:384-5.
(3) Leigh RJ, Zee DS. The neurology of eye movements. 3rd ed. Oxford University Press, 1999, pp. 19-89.
(4) Brandt T and Dieterich M. Central vestibular syndromes in roll, pitch, and yaw planes. Neuro-Ophthalmol 1995;15;291-303.
(5) Brodsky MC and Donahue SP. Primary oblique muscle overaction: the brain throws a wild pitch. Arch Ophthalmol (in press).
We thank Dr Ergun and Dr Stur [1] for their interest in our paper and agree with their comments that it is not possible to directly compare a pilot study with the results of a randomized controlled study. We also pointed out in our conclusion that studies such as this one cannot prove efficacy of a treatment but only indicate fruitful areas of further research. We also pointed out that the angiographic fo...
We thank Dr Ergun and Dr Stur [1] for their interest in our paper and agree with their comments that it is not possible to directly compare a pilot study with the results of a randomized controlled study. We also pointed out in our conclusion that studies such as this one cannot prove efficacy of a treatment but only indicate fruitful areas of further research. We also pointed out that the angiographic follow-up data were not complete, as once membrane closure was obtained the patients were followed up clinically.
The issue of the laser spot size in Transpupillary thermotherapy (TTT) is confusing, however it is known that more irradiance (W/cm2) is needed for smaller laser spots because heat conduction from choroidal blood flow cools smaller spots more efficiently than larger spots. This physiological phenomenon was established in experiements [2], theoretical [3], and clinical [4] studies. Furthermore, it is true that overlapping zones occur when multiple spots are used for very large treatment areas. Nonetheless, these zones experience the same temperature rise as every other treated area and no clinical abnormalities have been noted in the small overlapping zones. Although TTT is mainly used for occult membranes our results indicate that it may have a place in classic membranes and in this study stabilization of vision was obtained in the majority of these patients and in a minority an improved vision was noted.
References
(1) Ergun, E. and Stur, M. Transpupillary thermotherapy in choroidal neovascularization (letter). Brit J Ophthalmol 2001;85: 1014.
(2) Mainster, MA and Reichel E. Transpupillary thermotherapy for age-related macular degeneration: long-pulse photocoagulation, apoptosis, and heat shock proteins. Ophthalmic Surg Lasers 2000;31(5):359-73.
(3) Mainster, MA, White, TJ, et al. Spectral dependence of retinal damage produced by intense light sources. J Opt Soc Am 1970;60(6):848-55.
(4) Reichel E, Berrocal, AM, et al. Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration. Ophthalmology 1999;106(10):1908-14.
(5) Wolbarsht, ML. Safety with Lasers and Other Optical Sources: A Comprehensive Handbook. New York, Plenum Press 1980; pp. 130-1.
As one of the most "overtrained"(!) ophthalmologists in the UK at the
present time, I was delighted and stimulated to read the excellent,
erudite and witty Commentary by James Acheson in the recent edition of the
British Journal of Ophthalmology 2001;85:383-384. I think that the issue
that lies at the heart of the matter is, as Mr. Acheson himself puts it,
"It all depends on what you mean by training ....
As one of the most "overtrained"(!) ophthalmologists in the UK at the
present time, I was delighted and stimulated to read the excellent,
erudite and witty Commentary by James Acheson in the recent edition of the
British Journal of Ophthalmology 2001;85:383-384. I think that the issue
that lies at the heart of the matter is, as Mr. Acheson himself puts it,
"It all depends on what you mean by training . . . ." Surely one of the
driving reasons behind the length of all specialist training in the UK has
always been the high demands of the service commitment of the SHO and
Registrar grades alike. Until the issue of doctors' numbers can begin to
be tackled at a meaningful level in the UK we shall forever have the push-
pull politics of service versus training. It is still worth pointing out
that we have the lowest number of doctors per capita in the developed
world, bar only Greece and Albania.
It is also very true that the standards of ophthalmology training in
the UK are regarded very highly by trainees from oversees, who regularly
come to the UK to complement and polish off their training. However, they
come mainly for subspecialty training and often go to super-specialist
regional centers, where they act as Fellows, often in a somewhat
privileged position. They are able to benefit from the high level of
internationally renowned expertise in their chosen field, that the UK is
still able to provide. We in the UK face a rather unique situation, in
that super-specialist Fellowship training is quite rightly becoming the
norm whilst still being outside the national Calman Training Programme.
This sends a very mixed message about its value to the powers that be. It
is also far from easy for every trainee to find a suitable Fellowship and
funding.
So, on one hand the length of training could be shortened by tackling
the issue of service versus training demands, and on the other hand
perhaps training could formally be lengthened to ensure that British
ophthalmologists are able to stay at the forefront of their chosen fields
in the international arena.
A most outstanding research article that merits full praise to all of the authers.One of the best and furthermore the most useful article that I have read in a very long time.
I refer to the interesting article by Maar et al [1] published in Br J Ophthalmol 2001; 85: 47-51. The authors should be congratulated for presenting a new method of screening for diabetic macular oedema, however the paper contains some statistical errors, and I believe the results can be interpreted in other ways.
Firstly, there are some internal inconsistencies with some of the results reported in the...
I refer to the interesting article by Maar et al [1] published in Br J Ophthalmol 2001; 85: 47-51. The authors should be congratulated for presenting a new method of screening for diabetic macular oedema, however the paper contains some statistical errors, and I believe the results can be interpreted in other ways.
Firstly, there are some internal inconsistencies with some of the results reported in the paper. Specificity of the Mollon T test (Score>1) for detecting clinically significant macular oedema (CSMO) was reported as 88.9% and specificity was reported as 99.3%. These values could not possibly be obtained with the subject numbers specified, and I believe they have been erroneously published.
From other data provided by Maar et al [1] we are able to reconstruct values for these statistics. The mean Mollon T score and SD for non-CSMO patients implies 28 non-CSMO patients passed the test (true negatives) and one failed (false positive). The number of eyes with CSMO was 10 and there were 29 eyes without CSMO. The following table can be constructed:
No CSMO
CSMO
Total
Test negative
28
2
30
Test positive
1
8
9
Total
29
10
39
It is apparent from this table that the sensitivity of the test is 8/10 or 80.0% and not 88.9% and the specificity of the test is 28/29 or 96.6% and not 99.3% as quoted in the paper.
These values are of course only estimates of the true specificity and sensitivity and are based on fairly small numbers of subjects. It is good practice to report such figures accompanied by the 95% confidence intervals of these proportions.[2] For the purpose of assessing the practical value of a screening tool the lower confidence limit of the proportion is of clinical interest because it reflects the sensitivity and specificity of this test in the 'worst' scenario. Various methods could be used to calculate or approximate such an interval. For example, using the Wilson's Score method incorporating continuity correction,[3] the 95% CI of the sensitivity is 44.2%-99.1% and the specificity is 80.4%-99.8%. The clinician will be quick to notice the wide confidence interval for the sensitivity. This is an inherent problem in such studies, where the absolute number of cases of CSMO is relatively small. Thus it is possible that the Mollon Test is only a mediocre indicator of the presence of CSMO and the high sensitivity was obtained by chance.
The authors have mentioned that 'the Mollon-Reffin test was a better predictor than the other tests because it had a lower false positive rate (1-specificity)' in the legend to the Figure 3 of their paper.[1] Perhaps it would be better (but not mandatory) to present the area under the receiver operator curves (ROC). This will state the probability of correctly identifying a randomly selected participant as a case or non-case and is therefore a measure of overall test validity. This will also offer an objective way of comparing different ROCs. I also note that the shape of the ROC for the DD-15 test was unusual (some sensitivity values were associated with 2 different specificity values). It is difficult to conceive of a data set that could generate a non-montonic ROC curve and some comment on its unusual shape might have been useful.
Louis Tong
Andrew Carkeet
Singapore National Eye Centre
References
(1) Maar N, Tittl M, Stur M, et al. A new colour vision arrangement test to detect functional changes in diabetic macular oedema. Br J Ophthalmol 2001; 85: 47-51.
(2) Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998;17:857-872.
(3) Blyth CR, Still HA. Binomial confidence intervals. Journal of the American Statistical Association 1983, 78: 108-116.
We read with great interest the excellent Editorial by Ciulla [1] which describes pathophysiological paradigms for age related macular degeneration (ARMD) and the development of choroidal neovascular membranes (CNVM). We were particularly pleased to note that Ciulla [1] considered that 'whatever the initial stimulus for CNVM formation, it is clear that angiogenic growth factors are ultimately involved.' Furtherm...
We read with great interest the excellent Editorial by Ciulla [1] which describes pathophysiological paradigms for age related macular degeneration (ARMD) and the development of choroidal neovascular membranes (CNVM). We were particularly pleased to note that Ciulla [1] considered that 'whatever the initial stimulus for CNVM formation, it is clear that angiogenic growth factors are ultimately involved.' Furthermore, he observed that primary vascular changes in the choroid may also be responsible.
In light of these observations, we had hypothesised a relationship between abnormal vascularisation (angiogenesis), haemorheological factors and endothelial dysfunction in patients with ARMD. We felt that abnormalities in the systemic and choroidal vasculature, may relate to the release of angiogenic factors and subsequent proliferation of choriocapillaris through a defect in Bruch's membrane in susceptible individuals. To investigate this hypothesis further, we recently reported a cross-sectional study [2] of patients presenting with ARMD and measured plasma levels of VEGF (an index of angiogenesis), haemorheological factors (fibrinogen, plasma viscosity) and von Willebrand factor (an index of endothelial damage/dysfunction) from these patients. Median plasma VEGF [225 vs 195pg/ml, p=0.019] and mean von Willebrand factor [124 vs 99 IU/dL, p=0.0004] levels were higher in ARMD patients compared to healthy controls. Mean plasma fibrinogen and plasma viscosity levels were also higher in the patients [both p<_0.0001. our="our" observations="observations" would="would" therefore="therefore" suggest="suggest" further="further" pathophysiological="pathophysiological" insights="insights" into="into" armd="armd" with="with" an="an" association="association" between="between" this="this" disorder="disorder" and="and" markers="markers" of="of" angiogenesis="angiogenesis" vegf="vegf" haemorheological="haemorheological" factors="factors" haemostasis="haemostasis" endothelial="endothelial" damage="damage" dysfunction.p="dysfunction.p"/>
Rather than the existence of individual pathogenic processes [1], perhaps a close interaction between abnormal angiogenesis and the components of Virchow's triad for thrombogenesis may contribute to the pathogenesis of ARMD, and the development of CNVM. Indeed, the availability of a blood marker for ARMD could have potential value, as measurement of such a marker can be a non-invasive way of perhaps predicting individuals at high risk of developing ARMD. We have recently applied such a concept (that is, a blood marker to monitor the progression of eye disease) in a study of plasma VEGF in diabetic proliferative retinopathy, where the high plasma levels were normalised at 4 months follow-up, following treatment with pan-retinal laser photocoagulation [3].
Peck-Lin Lip (1,2)
Gregory YH Lip (2)
(1) The Birmingham and Midland Eye Centre, City Hospital, Birmingham, England;
and
(2) Haemostasis Thrombosis and Vascular Biology Unit,
University Department of Medicine, City Hospital, Birmingham;
References
(1) Ciulla TA. Evolving pathophysiological paradigms for age related macular degeneration. BJO 2001; 85: 510-12.
(2) Lip PL, Blann AD, Hope-Ross MW, Gibson J. Lip GYH. Age-Related Macular Degeneration Is Associated With Increased Vascular Endothelial Growth Factor, Hemorheology and Endothelial Dysfunction. Ophthalmology 2001;108:705-10
(3) Lip PL, Belgore F, Blann AD, Hope-Ross MW, Gibson JM, Lip GYH. "Plasma VEGF and Soluble VEGF Receptor Flt-1 in Proliferative Retinopathy: Relationship to Endothelial Dysfunction and Laser Treatment." Investigative Ophthalmology & Visual Science 2000; 41: 2115-19.
In reply to the comments of Stodtmeister and colleagues [1] on our recent paper [2], we won´t argue the correlation between central corneal thickness (CCT) and intraocular pressure (IOP), but we mistrust the clinical application of correcting factors. Stodtmeister et al compare our study to that of Ehlers et al [3] which is often cited to prove an influence of corneal thickness on applanatory measurement.
...
[Please note that the tables for this letter will be available in the December issue of BJO.]
In the recent paper by Feltgen et al [1], the intraocular pressure was measured by Goldmann applanation tonometry and by using a cannula inserted into the anterior chamber connected with a pressure transducer. Thus the measurement took place omitting a possible influence of the cornea on the result. Marx et al[...
The report of Mauriello et al. "Adenoid squamous carcinoma of the conjunctiva -- a clinicopathologic study of 14 cases" [1] has profoundly impressed us as plastic and reconstructive surgeons who encounter the problem of exenteration or enucleation. Facial plastic surgeons are most frequently asked to reconstruct the exenterated orbit, but also often meet the patient before surgery when the decision for exentera...
We read with interest the excellent article by Shah et al. [1] The authors compared the outcomes of epithelial debridement for photorefractive keratectomy (PRK) with those of epithelial flap for PRK. They used 20% ethanol for 30 seconds and 45 seconds for the debridement and flap techniques, respectively. They observed that epithelial flap resulted in faster visual rehabilitation and reduced haze. We have ob...
We were excited to see the recent case report of Park et al regarding the 30 year old man with horizontal locked-in syndrome and disconjugate gaze.[1] We were intrigued by the description of his eye movements on attempted horizontal gaze, whereas "when the patient was asked to look to the right side, the right eye moved upward with intorsion, and at the same time, left eye moved downward and extorsion ... when...
Dear Editor
We thank Dr Ergun and Dr Stur [1] for their interest in our paper and agree with their comments that it is not possible to directly compare a pilot study with the results of a randomized controlled study. We also pointed out in our conclusion that studies such as this one cannot prove efficacy of a treatment but only indicate fruitful areas of further research. We also pointed out that the angiographic fo...
Editor,
As one of the most "overtrained"(!) ophthalmologists in the UK at the present time, I was delighted and stimulated to read the excellent, erudite and witty Commentary by James Acheson in the recent edition of the British Journal of Ophthalmology 2001;85:383-384. I think that the issue that lies at the heart of the matter is, as Mr. Acheson himself puts it, "It all depends on what you mean by training ....
A most outstanding research article that merits full praise to all of the authers.One of the best and furthermore the most useful article that I have read in a very long time.
I refer to the interesting article by Maar et al [1] published in Br J Ophthalmol 2001; 85: 47-51. The authors should be congratulated for presenting a new method of screening for diabetic macular oedema, however the paper contains some statistical errors, and I believe the results can be interpreted in other ways.
Firstly, there are some internal inconsistencies with some of the results reported in the...
We read with great interest the excellent Editorial by Ciulla [1] which describes pathophysiological paradigms for age related macular degeneration (ARMD) and the development of choroidal neovascular membranes (CNVM). We were particularly pleased to note that Ciulla [1] considered that 'whatever the initial stimulus for CNVM formation, it is clear that angiogenic growth factors are ultimately involved.' Furtherm...
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