Recently, Cahill et al. published a paper on pupillary autonomic denervation in diabetic patients. In our own recent study we can confirm the presence of a small dark-adapted pupil size (DAP) before cardiovascular autonomic dysfunction is detected in patients with type-1 diabetes mellitus. We believe that this is an important observation, since autonomic alterations may cause an increase in mortality as...
Recently, Cahill et al. published a paper on pupillary autonomic denervation in diabetic patients. In our own recent study we can confirm the presence of a small dark-adapted pupil size (DAP) before cardiovascular autonomic dysfunction is detected in patients with type-1 diabetes mellitus. We believe that this is an important observation, since autonomic alterations may cause an increase in mortality as repeatedly evidenced for cardiac autonomic neuropathy (CAN).
In particular, we found a significantly reduced DAP in patients with normal ranges in high frequency waves of heart spectral analysis as a marker for cardiac parasympathetic nerve lesions and in variation coefficient of heart rate variability. Like Cahill et al., we could also show significant reduced pupillary responses to cocaine 4% eye drops in patients with CAN as a test for sympathetic nerve alterations. The DAP of patients with CAN did not yield significant differences with the age-matched controls. Patients without any systemic diabetic long-term complication defined as CAN, peripheral sensomotor neuropathy, retinopathy and nephropathy had no significant differences in their DAP as compared to the probands.
Thus, it is of interest if in this study patients with CAN also significantly differ in their pupillary responses to cocaine, and if patients without CAN possibly have other diabetic long-term complications or increased gylcosylated hemoglobin levels, which may correlate with the small DAP.
Nevertheless, this study by Cahill et al. also clearly indicates that screening for pupillary dysfunction is mandatory as early as possible to prevent the sequelae of other autonomic neuropathic disorders.
(1) Cahill M, Eustace P, de Jesus V. Pupillary autonomic denervation with increasing duration of diabetes mellitus. Br J Ophthalmol 2001; 85: 1225-30.
(2) Pittasch D, Lobmann R, Behrens-Baumann W, Lehnert H. Autonomic sympathetic neuropathy of the pupil in patients with diabetes mellitus type 1. Exp Clin Endocrinol Diabetes 2000; suppl. 1: S37.
(3) McNally PG, Lawrence IG, Panerai RB, Weston PJ, Thurston H. Sudden death in type-1 diabetes. Diab Obes Metabol 1999; 1:151-8.
(4) Sharma S, Hoskin-Mott A, Benstead T, Maxner C. Correlation of the pilo-pupil ratio average, a new test for autonomic denervation, to the severity of diabetic retinopathy. Can J Ophthalmol 1997; 32.170-4.
Miyata and colleagues have elegantly described an interesting and rare complication of phototherapeutic keratectomy (PTK) in their recent report of an unusual case of keratectasia after PTK. The hypothesis that risk of ectasia is proportional to residual stromal base, or depth of ablation, fits with the assumed biomechanical aetiology of this recently reported complication of laser refractive surgery. The gene...
Miyata and colleagues have elegantly described an interesting and rare complication of phototherapeutic keratectomy (PTK) in their recent report of an unusual case of keratectasia after PTK. The hypothesis that risk of ectasia is proportional to residual stromal base, or depth of ablation, fits with the assumed biomechanical aetiology of this recently reported complication of laser refractive surgery. The generally accepted empirical minimum thickness of 250-300µm of corneal stroma, excluding flap thickness, remains speculative, as we do not understand the underlying pathophysiology. Indeed, although Holland et al highlighted the association of thin residual stromal thicknesses, post PRK and LASIK, with keratectasia, they also described this complication after surface based Hypermetropic-PRK ablation, where the centre was minimally ablated and residual stromal thickness was greater than 360µm.
The authors suggest, in the reported case, that Band Shaped Keratopathy (BSK) may have compromised the tensile strength of the cornea. This seems unlikely as this condition generally affects the superficial anterior cornea, and usually does not penetrate deeper than Bowman's, hence its suitability for treatment by PTK. However, further clinical detail which the authors have not provided might reveal underlying corneal pathology with secondary "rough" BSK, rather than "smooth" BSK.
However, there are a number of alternative reasons, other than simple biomechanical compromise, for keratectasia following PTK in this case.
A) Forme fruste keratoconus - as no pre-op topography or surface asymmetry values are presented to enable the reader to rule this out.
B) Clinical keratoconus - which seems less likely in respect to patients age and a pre-operative cylindrical error of only -1.5D.
C) Idiopathic keratectasia - possibly secondary to widespread de-regulated keratocyte apoptosis. The latter has been demonstrated after LASIK, with a considerable and longstanding decrease in keratocytes in the peri-ablation area. Also, Helena et al (1998) demonstrated apoptosis to a depth of at least 50µm following all the procedures: epithelial scrape, corneal scrape PTK, transepithelial PRK, and LASIK. Epithelial scrape and LASIK demonstrated keratocyte apoptosis to depths of up to 75µm and 100µm respectively. The authors have recently identified a keratocyte free zone 160µm into the stroma following LASIK, and theoretically more widespread apoptosis as a response to excimer laser photorefractive surgery, which may contribute to keratectasia.
Whilst it is difficult to ascertain why keratectasia occurs, in this case with a residual stromal thickness of over 500µm, from the data provided the most likely aetiologies would seem to be either undiagnosed forme fruste keratoconus or idiopathic keratectasia. Currently recent reviews illustrate the dearth of substantial information available regarding idiopathic keratectasia (iatrogenic keratoconus), with a little over 50 cases published. At this point in time, although some are likely to be due to over-ablation, for many cases such as this the exact aetiology remains unknown and is likely to be multifactorial, and one of these factors is residual corneal thickness. The fact that keratectasia can occur, after what would be considered minimal ablation, highlights the unpredictability of occurrence, but with over a million cases of LASIK or PRK occurring each year, the stimulus to identify contributing factors is significant.
Dr Simon J Dean MB ChB
Professor Charles N J McGhee
Discipline of Ophthalmology, Faculty of Medicine and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
(1) Miyata K. Takahashi T. Tomidokoro A. Ono K. Oshika T. Iatrogenic keratectasia after phototherapeutic keratectomy. Br J Ophthalmol 2001; 85: 247-8
(2) Holland SP. Srivannaboon S. Reinstein DZ. Avoiding serious corneal complications of laser assisted in situ keratomileusis and photorefractive keratectomy. Ophthalmology 2000; 107(4):640-52
(3)Vesaluoma M. Perez-Santonja J. Petroll WM. Linna T. Alio J. Tervo T. Corneal stromal changes induced by myopic LASIK Investigative Ophthalmology & Visual Science 2000; 41(2):369-76
(4)Helena MC. Baerveldt F. Kim WJ. Wilson SE. Keratocyte apoptosis after corneal surgery. Investigative Ophthalmology & Visual Science 1998; 39(2):276-83,
(5)Edwards M. Kent D. McGhee CNJ. Idiopathic keratectasia (Iatrogenic keratoconus). J CME Ophthalmol (in press)
This series is certainly the largest ever reported in west Africa . However, it is worth noting that Xeroderma Pigmentosum (XP) has already been described in two Mauritanian half cousins in France . Two isolated cases have been reported in Senegal and Cameroon, respectively [3,4]. The skin of black people, rich in melanin provides some protection from the oncogenic effects of ultraviolet rays. It is possib...
This series is certainly the largest ever reported in west Africa . However, it is worth noting that Xeroderma Pigmentosum (XP) has already been described in two Mauritanian half cousins in France . Two isolated cases have been reported in Senegal and Cameroon, respectively [3,4]. The skin of black people, rich in melanin provides some protection from the oncogenic effects of ultraviolet rays. It is possible, in my opinion, that it prevents the occurrence of skin lesions in subclinical forms and reduces the frequency of XP. This hypothesis raises the question of the protection of mucosae.
In south Cameroon where the sickle cell trait affects up to 40% of the population, it is well known among the Bantu tribes that marriages within the same clan is not allowed. The people still consider themselves brothers and sisters in the same clan even after an exponential number of generations. Consequently, there is a low coefficient of consanguinity concerning all hereditary disorders with an autosomal recessive transmission mode.
(1) Ahmed H, Hassan R, Pindiga U. Xeroderma pigmentosum in three
consecutive siblings of a Nigerian family: observations on oculocutaneous manifestations in black African children. Br J Ophthalmol 2001; 85: 110.
(2) Bouzamel F, Sarasin A, Fohlen M, Blanchet-Gardon C. Xeroderma
pigmentosum associé à un syndrome de Cockayne. Ann Dermatol Veneorol (Paris) 1992; 119: 823-825.
(3) Ndiaye B, Ball MD, Strobel M, Niang I. Xeroderma pigmentosum. Première observation sénégalaise. Dakar Médical 1983; 28: 167-172.
(4) Moussala M, Behar-Cohen F, D'Hermies F, Bisseck AC, Renard G. Le
xeroderma pigmentosum et ses manifestations oculaires. A propos du premier cas camerounais. J Fr Ophtalmol 2000; 23(4): 369-374.
We read with interest the article titled "Failure of amniotic membrane transplantation (AMT) in the treatment of acute ocular burns" by Joseph et al. It is to be appreciated that they have come forward to report the negative results of their study along with the need of an upgraded classification for the chemical burn. The authors must be congratulated for highlighting the pitfalls of the AMT in acute cases w...
We read with interest the article titled "Failure of amniotic membrane transplantation (AMT) in the treatment of acute ocular burns" by Joseph et al. It is to be appreciated that they have come forward to report the negative results of their study along with the need of an upgraded classification for the chemical burn. The authors must be congratulated for highlighting the pitfalls of the AMT in acute cases with sufficient scientific explanation.
Whenever a new technique is described, it is aggressively followed without realizing the consequences. The authors have very rightly suggested that the most important strategy for the management of thermal and chemical burns in the acute stage is to reduce inflammation, promote vascularization of the ischaemic ocular surface and epithelialisation of the cornea. It is reported in the literature that AMT does help in all these 3 conditions at acute stage of burn for which the procedure is advocated. but when and to what stage? It is essential to have some amount of healthy conjunctival tissue for graft to take up. Further, rather than performing the AMT at an acute stage, some gap should be given between burn and surgery. This may help to reduce inflammation, thus, allowing the surgeons to perform an elective surgery. As regards to the stage of the chemical burn, the author has very rightly pointed out that there is a remarkable limitation in modified Roper Halls classification at grade IV. Do the eyes with 100% limbal ischaemia behave the same as those with 55% ischaemia1.
Dating back to 1984 it was thought of and a modified classification was suggested in these eyes prior to keratoplasty as a prognostic factor. However, the same was restricted to healed lesions and now the time has come the modification is needed for acute lesions.
Once again we would like to commend the authors for their boldness and wonder how many of the corneal surgeons would have felt the same.
(1) Joseph A, Dua HS, King AJ. Failure of amniotic membrane transplantation (AMT) in the treatment of acute ocular burns. Br. Jour Ophthalmol 2001;85:1065-9.
(2) Mellor D, Renato TF, Pires et al. AMT for acute chemical or thermal burns. Ophthalmology 2001;107:980-90.
(3) Roper Hall MJ. Thermal and chemical burns. Trans ophthalmol soc UK 1965;85-631-40.
(4) Panda A, Mohan M, Gupta AK, Chowdhary S. Keratoplasty in alkali burned corneas. Indian J. Ophthalmol 1984;32:441-6
I read with interest the article by Ekatomatis  on latanoprost treatment for primary open angle glaucoma causing herpes simplex dendritic keratitis. He should be applauded for reporting a serious side effect of latanoprost. His assertion however that latanoprost has been known to have almost no serious side effects is not entirely accurate. In fact, Wand et al  reported three patients who developed herp...
I read with interest the article by Ekatomatis  on latanoprost treatment for primary open angle glaucoma causing herpes simplex dendritic keratitis. He should be applauded for reporting a serious side effect of latanoprost. His assertion however that latanoprost has been known to have almost no serious side effects is not entirely accurate. In fact, Wand et al  reported three patients who developed herpes simplex dendritic keratitis after therapy with latanoprost for primary open angel glaucoma. One patient with a previous history of herpes simplex keratitis had a recurrence while taking latanoprost, and resolved when latanoprost was discontinued. When rechallenged with latanoprost the patient again developed herpes simplex dendritic keratitis. A second patient with a history of bilateral herpes simplex dendritic keratitis had recurrence in both eyes on latanoprost treatment, confirmed on viral cultures, which only resolved on discontinuation of latanoprost and the start of antiviral treatment. When rechallenged with latanoprost therapy with concurrent prophylactic antiviral medication, the cornea remained clear. With discontinuation of antiviral suppression, herpes simplex dendritic keratitis recurred.
Using a rabbit model, Kaufman et al  have confirmed a relationship between latanoprost therapy and the recurrence and severity of herpes simplex keratitis. Latanoprost is a potent prostaglandin F2a analogue. Ekatomatis proposed biochemical disturbance of the surface of the cornea as a mechanism through which latanoprost causes recurrence of keratitis. It is more likely that prostaglandins, known to enhance the multiplication of herpes viruses , may be a common final pathway in herpes simplex keratitis recurrence. A multi-centre double blind case controlled study is required to clarify the side effect profile of this commonly used drug.
(1) Ekatomatis P. Herpes simplex dendritic keratitis after treatment with latanoprost for primary open angle glaucoma. Br J Ophthalmol 2001;85;1008-9.
(2) Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes simplex keratitis. Am J Ophthalmol 1999;127:602-4.
(3) Kaufman HE, Varnell ED, Thompson HW. Latanoprost increases the severity and recurrence of herpetic keratitis in the rabbit (comment). Am J Ophthalmol 1999;127;531-6.
(4) Harbour DA, Blyth WA, Hill TJ. Prostaglandins enhance spread of herpes simplex virus in cell structures. J Gen Virol 1978;41:87-95.
The study is a good comparison of the two medications. I have a few queries for the authors:
1) Why is latanoprost causing an increase in iris pigmentation; is that not a cause for concern and should this serious side effect not be investigated more fully?
2) Latanoprost increases uveoscleral outflow; does it bypass the
trabecular meshwork or is it causing any blockage in aqueous outflow from th...
2) Latanoprost increases uveoscleral outflow; does it bypass the
trabecular meshwork or is it causing any blockage in aqueous outflow from the angle of the anterior chamber? If such is the case, that an
alternative pathway is being forced to function through drug stimulation, will that not cause a decrease or even a complete stoppage of the function of the normal outflow path?
3) Patients develop drug resistance to beta-blockers after a period of time. Has Latanoprost been studied for this troublesome long-term side effect? Because I believe that any drug that is used for a lengthy period of time has a big chance of inducing drug resistance.
We read with interest the article entitled 'Combined phacoemulsification and transpupillary drainage of silicone oil: results and complications'. We similarly removed silicone oil through the posterior capsulorhexis along with phacoemulsification. We used an inferotemporal infusion cannula in the pars plana region in all except the first two eyes where intraoperative choroidal detachment ocurred. Similar in...
We read with interest the article entitled 'Combined phacoemulsification and transpupillary drainage of silicone oil: results and complications'. We similarly removed silicone oil through the posterior capsulorhexis along with phacoemulsification. We used an inferotemporal infusion cannula in the pars plana region in all except the first two eyes where intraoperative choroidal detachment ocurred. Similar infusion ports were also used by Larkins et al.. The authors have used a 20 gauge Rycroft cannula introduced through the corneal incision to drain out the silicone oil through the posterior capsulorhexis. However, we have used the automated irrigation aspiration probe which helps to actively aspirate the small emulsified or partially emulsified droplets of silicone oil. The larger bubbles of silicone oil are flushed by hydrodynamic expression due to the irrigating fluid from the corneal incision. Furthermore, these eyes have decompensated zonules from prior vitreoretinal surgery and are more prone to 'infusion deviation syndrome'. Anterior chamber may become shallow during phacoemulsification. However, increasing the bottle height only paradoxically worsens the situation as the fluid
migrates posteriorly through the zonular network and increases the volume of posterior segment compartment and thereby increases the shallowing of the anterior chamber.
Combined phacoemulsification and transpupillary drainage of the silicone oil through a planned posterior capsulorhexis is indeed a useful procedure in the absence of macular pucker and retinal reproliferation.
(1) Assi A, Woodruff S, Gotzaridis E,Bruce C, Sullivan P. Combined
phacoemulsification and transpupillary drainage of silicone oil: results and complications. Br J Ophthalmol 2001,85:942-945
(2) Dada VK, Talwar D, Sharma N, Dada T, Sudan R, Azad RV. Phacoemulsification combined with silicone oil removal through a posterior capsulorhexis. J Cataract Refract Surg 2001;27: 1243-1247
(3) Larkin GB, Flaxel CJ, Leaver PK. Phacoemulsification and silicone oil removal through a single corneal incision. Ophthalmology 1998; 11: 2023-2034
In reply to the comments of Stodtmeister and colleagues  on our recent paper , 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  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  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  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 . 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  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  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  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 . Therefore, we renew our warning to recalculate the IOP depending on central corneal thickness.
(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 , 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[...
In the recent paper by Feltgen et al , 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 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  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  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  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
Dr. rer.biol.hum Martina Kron
Prof. Dr.phil. Wilhelm Gaus
University of Ulm
Department of Biometry and Medical Documentation
(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"  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"  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  considered epitheliomas involving the conjunctival fornices of the eyelids indicated for orbital exenteration. Moshfeghi et al  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  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 . 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
(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.