Mediators of the ocular inflammatory response to interleukin-1β plus tumor necrosis factor-α

Background: Intravitreal injection of marginally inflammatory doses of interleukin-1 and tumor necrosis factor- (IL-1 /TNF) has been shown to produce intraocular inflammation distinctly different from that induced by higher intravitreal doses of either IL-1 or TNF. Since cyclooxygenase inhibitors and platelet-activating factor (PAF)-receptor antagonists can reduce IL-1- or TNF-induced uveitis, the present investigation was undertaken to determine whether cyclooxygenase metabolites of arachidonic acid and PAF are important mediators of IL-1/TNF-induced uveitis. Methods: The cyclooxygenase inhibitor indomethacin and two structurally dissimilar PAF-receptor antagonists, SRI 63-441 and WEB 2086, were used to investigate the importance of cyclooxygenase metabolites and PAF in IL-1/TNF-induced uveitis. Results: Based upon the effectiveness of indomethacin, the anterior uveitis induced by IL-1/TNF could be divided into two phases; a primary phase dependent upon generation of cyclooxygenase metabolites (the first 24 h) and a secondary phase largely independent of cyclooxygenase metabolite production (24–48 h). Posterior uveitis was also apparent at 48 h and was reduced by indomethacin. SRI 63-441 reduced the anterior uveitis at 24 h and to a lesser extent at 48 h; it also reduced the posterior uveitis at 48 h. However, although WEB 2086 was as effective as SRI 63-441 in reducing PAF-induced platelet aggregation, ex vivo, it did not significantly reduce IL-1/TNF-induced uveitis. Conclusions: Although the findings do not support an important role for PAF in TNFa/IL-1-induced uveitis, it cannot be ruled out that more intensive treatment with a specific and long-acting PAF-receptor antagonist might yield more positive results.     

Prevalence of HTLV-1-associated uveitis in the Kanto Plain,Japan

Background: Seroprevalence of antibody to human T-lymphotropic virus type I (HTLV-I) is high in the island of Kyushu, Japan. Reports on the etiological analysis of HTLV-I in patients with uveitis primarily document cases in this island. We studied the seroprevalence of HTLV-I at the Department of Ophthalmology in Yokohama City University Hospital and in Odawara Municipal Hospital, which are in the Kanto Plain on the island of Honshu, Japan. Methods: The subjects were 741 patients who visited the two hospitals. The presence of serum antibodies against HTLV-I was assessed using the method of particle agglutination. Results: Of 454 patients with nonuveitic ocular diseases, 9 (1.98%) were seropositive. Of 143 patients with definite diagnosis of uveitis, 1 (0.70%) was seropositive. Of 144 patients with non-specific uveitis (etiology undefined), 8 (5.56%) were seropositive. Thus, the prevalence of serum antibodies to HTLV-I was higher in patients with non-specific uveitis than in patients with specific uveitis or nonuveitic ocular diseases. Common ocular symptoms of 8 HTLV-I-infected patients with non-specific uveitis were compatible with the clinical features of uveitis described as HTLV-I-associated uveitis (HAU). Conclusion: It is important to suspect HAU in patients with uveitis of unknown etiology, even outside known areas of prevalence.     

The effect of thalidomide and supidimide on endotoxin-induced uveitis in rats

Background: Endotoxin-induced uveitis (EIU) is an animal model of ocular inflammation, produced by footpad injection of endotoxin (lipopolysaccharide, LPS) to mimic the human disease of acute anterior uveitis, that is useful for testing new anti-inflammatory therapy. The purpose of this study was to test the anti-inflammatory effect on EIU of thalidomide and one of its derivatives, supidimide. Methods: EIU was produced in rats by hind footpad injection of LPS (100 g/animal). Animals were killed 20 h after LPS injection. Inflammation was evaluated by anterior chamber determination of proteins and cells. Results: A dosage of 400 mg/kg per day of thalidomide was efficient in reducing inflammation whether given in three doses (at – 24 h, – 4 h and + 4 h relative to LPS challenge = THAL-1; p < 0.001 for proteins and cells), in two doses (–4 h and +4 h = THAL-2; p < 0.001 for proteins, p < 0.012 for cells) or in one dose (at +4 h=late THAL; p < 0.001 for proteins, p0.02 for cells). A dosage of 300 mg/kg per day of thalidomide was still efficient (p0.023 for proteins, p0.06 for cells), but 150 mg/kg per day had no effect on inflammation. Supidimide (400 mg/kg per day) had some anti-inflammatory effect (p 0.053 for proteins, p < 0.06 for cells). Conclusion: High-dose thalidomide had a potent anti-inflammatory effect in EIU, but lower doses were not sufficient to reduce inflammation. At similar high doses, supidimide had some effect on EIU but was less effective than thalidomide.These data were presented in part at the first annual ECORA meeting, 4–6 October, 1993, Bonn, Germany     

The use of tissue plasminogen activator in post-traumatic total hyphaema

Background: We wanted to evaluate whether intracameral injection of tissue plasminogen activator (tPA) is useful in managing traumatic hyphaema. Methods: Two eyes with total hyphaema after a severe penetrating injury were treated with a single intracameral injection of 25 g of tPA 5 and 14 days after the injury, respectively. Results: Most of the blood coagulum dissolved within 24 h, and in one of the two eyes the intraocular pressure decreased from 45 to 8 mmHg. The other eye was hypotonic. No re-bleeding or complications related to the use of tPA were noticed. Conclusion: The results in these two cases suggest that tPA is a useful adjunct in managing total hyphaema.     

Orbital exenteration: Surgical and reconstructive strategies

Background: Radical exenteration procedures, which include the removal of orbital content and eyelids, result in serious functional limitations, especially with respect to eating and speaking. Therefore we have recently changed our surgical concept. Methods: Seventy-seven patients underwent orbital exenteration during the 20-year period from 1974 to 1995 at the Department of Maxillofacial Surgery, Essen University. The simultaneous removal of periorbital bone was performed in 45 of these cases. Results: The 1-year survival rate was 89%, the 5-year rate was 63% and the 10-year rate was 48%. The surgical approach, the amount of resected orbital tissue and the reconstructive procedure have been adapted to the individual needs, depending on the location and extent of the tumor. Subsequently, the surgical morbidity has decreased. Discussion: Detailed consideration of all clinical and histological findings is essential before surgery, in order to prevent a higher rate of recurrence following these modified operations.     

Adult-onset foveomacular vitelliform dystrophy and indocyanine green videoangiography

Background Adult-onset foveomacular vitelliform dystrophy (AOFVD) represents a heterogeneous group of disorders with different clinical, angiography, and histopathological features. The most common form is characterized by a yellow, round to oval subretinal macular lesion with or without central pigmented spot. Methods Eight patients affected by typical AOFVD underwent fluorescein an giography and indocyanine green videoangiography (ICGV). Results Fluorescein angiography showed a central hypofluorescent spot surrounded by an irregular hyperfluorescentring ICGV demonstrated a foveal nonfluorescent spot, visible during the entire examination, and a hyperfluorescent area surrounding the central spot, which became evident soon after the beginning of the examination. Conclusions In light of previous histopathological studies, the central nonfluorescent spot may be interpreted as a masking effect of a pigment clump, whereas the hyper-fluorescent area may represent dye pooling or staining of the subretinal pigment epithelial material.     

Precision of ultrasonic estimates of choroidal melanoma regression

Background: Important prognostic information may be gained from knowledge of the volume and, over time, the change in volume of intraocular tumours such as choroidal melanomas. Methods: The precision and time consumption of three different ultrasonographic methods were evaluated. Seven choroidal melanomas were analysed after placement of a ruthenium plaque and again after tumour regression had occurred. Perpendicular ultrasound B-scans were printed and analysed by overlay grid counting or outline tracing of tumour structures to calculate the volume. These two methods, using only two perpendicular scans, were compared with a micro-computer-controlled ultrasonographic three-dimensional rotation scanning system, where each tumour was manually outlined in 20 revolving scan planes. Results: The three-dimensional volume scanning method was the most precise, but also the most demanding in hardware and time consumption. Conclusion: Increased precision and less observer-dependent estimation of shrinkage rate after radiotherapy is available at the cost of sophisticated equipment.     

Silent myocardial ischemia in glaucoma and cataract patients

Background: Glaucoma and cataract are multifactorial diseases. They have been described to be associated with cardiovascular risk factors. Methods: Twentyfour-hour ECG monitoring was done in 22 normal-tension glaucoma patients, 27 open-angle glaucoma patients, 25 cataract patients, and 20 normal controls. The frequency of silent myocardial ischemia (SMI) as well as that of ventricular extrasystoles (VES) was evaluated. Results: At least one episode of significant asymptomatic ST-T segment depression occurred in 45% of the normal-tension glaucomas, in 25.9% of open-angle glaucomas, in 12% of cataract patients, and in 5% of normal controls. The frequency of VES was not significantly different among the groups. Conclusions: Glaucoma, especially normal-tension glaucoma, is significantly associated with the occurrence of episodic asymptomatic myocardial ischemias. Cataract patients, however, had only a slightly, statistically not significantly increased frequency of both SMI and VES compared with normals.     

Self-assessment of angles of strabismus with photographic Purkinje I and IV reflection pattern evaluation

Background: Accurate assessment of the angle of strabismus, e.g. of variable angles of strabismus, is crucial in preoperative patient management and is usually performed in a clinical environment. Objective assessment by patients themselves, under everyday conditions, could contribute to a better preoperative work-up. A new objective evaluation procedure for the measurement of manifest angles of strabismus for near and distance fixation by the patient himself is presented. Methods: To account for the modified experimental setup used for the self-assessment, an amended computation procedure of Purkinje reflection pattern evaluation was developed. For measurement, patients and controls placed their head on a head/chin rest and fixated at 33 cm or 4 m distance in primary position. A reflex camera and three photo flash units were positioned on a special frame underneath the visual axis and in front of the subject so that both eyes could be photographed simultaneously. The camera's remote shutter control was released together with the photo flash units by the properly fixating subject. The angles of strabismus were obtained from the series of pictures through later evaluation of the Purkinje I and IV reflection patterns recorded in the photographs of the eyes. Results: Measurements of the ocular alignment in two control groups and in a group of strabismic subjects showed satisfactory accuracy of the self-assessment method compared to standard Purkinje reflection pattern evaluation and orthoptic measurements of the angle of strabismus. Conclusion: The modified self-assessment method can be used for the objective recording of angles of strabismus as needed in the preoperative work-up of patients with variable angles of strabismus, over prolonged periods of time, and outside a clinical setting.Presented in part as a poster at the 88th Annual Meeting of the Deutsche Ophthalmologische Gesellschaft in Baden-Baden, 1990     

Corneal neovascularization in rats as a model for photothrombotic therapy using bacteriochlorin a and an argon laser

Background: The presence of vessels has a negative influence on corneal transplant survival. Closure of such vessels prior to transplantation may improve the transplant results, and this might be achieved by irradiating the vessels with argon laser light after intravenous administration of a photosensitizer, e.g. bacteriochlorin a (BCA). A suture-induced corneal neovascularization model in rats was set up to test this hypothesis. Methods: Suture-induced vessels in the cornea of male Wistar rats were irradiated with argon laser light after intravenous administration of BCA. We applied irradiation of varying energy levels and duration and assessed the changes in the vessels by slit-lamp examination, fluorescein angiography and histology. Results: Suture-induced corneal vessels in the rat could be used effectively to study photothrombosis therapy. Intravenous administration of BCA prior to irradiation (=514.5 nm) of the corneal vessels led to vessel closure at lower energy levels and of longer duration than occurred with laser treatment alone. Conclusion: Suture-induced corneal neovascularization in the rat can be used as a model to study the efficacy of photothrombosis therapy. BCA can be used to enhance the rate and duration of vessel closure.     

Hemodynamic parameter estimation from ocular fluorescein angiograms

Background: A method is proposed for parameterizing choroidal blood flow from fluorescein angiograms. Methods: After digitizing and aligning the angiographic sequence, the intensity build-up curves of fluorescence are analysed per pixel (approx. 10 m in fundo). Two models are compared. A one-compartment model predicts an exponential build-up curve, from which the following parameters are estimated: maximum fluorescence, dye appearance time and local perfusion rate (reciprocal of the time constant of the exponential). To account for the contribution of the systemic circulation to the shape of the build-up curve, a two-compartment model is used which predicts a bi-exponential curve. Results: Introduction of the second (systemic) compartment resulted in a significant improvement of fit in 37 of 48 patients studied. The rate constants of the systemic compartment found were mainly in the range of 0.30–1.00 s^–1. Conclusion: For the individual patient, the local perfusion rates may vary strongly, with lower perfusion rates possibly being of prognostic value for ocular diseases such as glaucoma or diabetic retinopathy.     

Detection of herpes simplex virus after penetrating keratoplasty by polymerase chain reaction: correlation of clinical and laboratory findings

Background: The study was carried out to investigate the possible correlation of clinical findings, histopathologic features and detection of herpes simplex virus DNA in corneal buttons obtained after penetrating keratoplasty. Methods: We examined 47 consecutive corneal buttons sent for histopathologic examination by light microscopy and using the polymerase chain reaction for the detection of HSV1 and HSV2. Twenty-one corneal buttons from eyes with bullous keratopathy served as controls. Results: The 47 cases were graded from the clinical information available as unproven, suspected and clinically proven cases of herpetic keratitis. This grading did not correlate to specific histopathologic features or to the results of HSV1 DNA testing. None of the cases were positive for HSV2 DNA. Conclusion: HSV DNA was detected in some of the cases of clinically unsuspected herpetic keratitis. This technique of demonstrating the presence or absence of HSV in the cornea after keratoplasty is more reliable than clinical data or histopathologic findings and may be important in cases of recurrent inflammatory episodes involving grafts after keratoplasty.Presented in part at the meeting Frontiers in Penetrating Keratoplasty on 22 September 1994, Heidelberg, Germany     

Inhibition of corneal allograft reaction by CTLA4-Ig

Background: Activation of T cells requires both the interaction of T-cell receptor with major histocompatibility complex on the antigen-presenting cell and costimulatory signals, for instance the B7 antigens expressed on antigen-presenting cells and the CD28 molecule expressed on T cells. A recombinant fusion protein, CTLA4-Ig, has been produced that contains the extracellular domain of human CTLA4 fused to IgGl constant region and that binds the B7 molecule with high affinity. Blocking the CD28/B7 interaction with CTLA4-Ig inhibits T cell activation in vitro and in vivo. Methods: We used CTLA4-Ig in a fully MHC-mismatched mouse keratoplasty model. The animals were divided into four groups: (1) no treatment, (2) intraperitoneal treatment with 130 g CTLA4-Ig, (3) intraperitoneal treatment with 300 g CTLA4-Ig, (4) subconjunctival treatment with 290 g CTLA4-Ig. Results: The allograft reaction occurred in untreated animals between days 12 and 16 (mean 13.5). While topical application of CTLA4-Ig seemed to shorten the graft survival (mean 11.6 days) and systemic application of 130 g had no influence (mean 14.0), only intraperitoneal injection of 300 g of CTLA4-Ig prolonged the survival of allografts (mean >20 days) (P<0.01). Conclusion: CTLA4-Ig prolonged significantly the survival of corneal allografts in a fully MHC-mismatched mouse keratoplasty model, but the small antigen load of the corneal transplant and the anterior chamber-associated immune deviation (ACAID) may have a disadvantage to induce tolerance in this model of CTLA4-Ig therapy.Presented at JERMOV 1996 in Montpellier     

Serum-induced collagen gel contraction

Purpose: To understand the molecular events underlying disease-related vitreous gel contraction, the effect of serum components on collagen was investigated. Methods: Bovine vitreous or dermal collagen was incubated with a mixture of transglutaminase (TG; factor XIIIa) and fibronectin (FN), and the biochemical changes of collagen were monitored by gel electrophoresis. In addition, serum-induced changes in the volume of the collagen gel were monitored. Results: Gel electrophoresis revealed a new high-molecular-weight band (M_r 240 000) presumably due to intermolecular cross-links of collagen peptides and FN. The serum components also were shown to cause a significant decrease in the volume of the collagen gel. Conclusion. Collagen gel contraction could be attributed to the collagen-FN-collagen cross-links catalyzed by TG.     

Experimental microendoscopic photoablative laser goniotomy as a surgical model for the treatment of dysgenetic glaucoma

Purpose: The aim of this study was to investigate the feasibility of photoablative Er:YAG laser goniotomy under microendoscopic control in a surgical cloudy corneal model of primary infantile glaucoma. Methods: Pectinate ligaments of 12 freshly enucleated cadaver porcine eyes were treated by ab interno single-pulse (5 mJ, 200 s) Er:YAG laser (2.94 m) photoablation. Through a clear corneal incision near the limbus an ophthalmic microendoscope (18 and 20 gauge) was inserted into the anterior chamber. Internal structures were observed and photoablative laser goniotomy was conducted under video guidance. Following treatment all eyes were prepared for light and scanning electron microscopy. Results: Anterior chamber angle structures and tissue photoablation were clearly visualized on the videoscreen using ophthalmic microendoscopy. Energy settings of 5 mJ per pulse proved to be sufficient for reproducible photoablation of pectinate ligaments, accompanied by the root of the iris falling back and exposing trabecular meshwork. This was confirmed histopathologically. Scatter thermal damage was less than 30 m. Conclusion: This new therapeutic modality, which combines endoscopic visualization of the internal structures with photoablative laser goniotomy, can be effective in the management of dysgenetic glaucoma in the presence of a cloudy cornea. High reproducibility of contact laser photoablation enabled sufficient control of incision depth and was not accompanied by inadvertent tissue damage to adjacent intraocular structures.     

Decorin and suramin inhibit ocular fibroblast collagen production

Background: The process of ocular wound healing with respect to glaucomatous filtering procedures is of current interest. Delaying this response in patients could possibly lead to more favorable surgical results. So far, only highly toxic antimetabolites have come into frequent clinical use. The possible efficacy of other groups of substances such as growth factor inhibitors has not yet been examined in vitro. Methods: We exposed Tenon's capsule fibroblasts in tissue culture to various concentrations of decorin and suramin. The dose responses of type I and type III collagen to these inhibitors were measured using an ELISA-type dot blot assay. Total cellular protein production was assayed by measuring the incorporation of tritiated leucine. Results: At a concentration of 10 g/ml, suramin reduced the collagen production by more than 80%. Decorin, at a concentration of 100 g/ml, reduced type I collagen production by about 50% while type III collagen was reduced by 80%. At these concentrations, the total cellular protein production was not inhibited. Conclusions: Both suramin and decorin, which specifically inhibit the action of growth factors on target cells, reduce the production of collagen synthesis by Tenon's capsule fibroblasts. This is a specific effect, because total protein production is not influenced. This sets these substances apart from antimetabolites. Decorin and suramin may have clinical relevance in that they appear to interfere with ocular wound healing more specifically than the substances so far frequently used.     

Expression of mRNA coding for TNFα, IL-1β and IL-6 by cells infiltrating retinal membranes

Background: Cellular mechanisms of inflammation are thought to be involved in the pathogenesis of proliferative vitreoretinopathy, and cytokines, which are products of cell activation, are known to play an important role in the development and maintainance of inflammatory reactions. It was the aim of this work to investigate the presence of cells expressing cytokine mRNA within retinal membranes. Methods The presence of mRNA coding for the cytokines interleukin 1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor (TNF) was investigated in 19 epiretinal membranes obtained from eyes undergoing vitrectomy for the treatment of retinal detachment complicated by proliferative vitreoretinopathy. Results Cells expressing mRNA for IL-1 were observed in 7 membranes, cells positive for IL-6 mRNA were seen in 12 membranes, and cells exhibiting mRNA for TNF were present in 9 specimens. Only three membranes contained cells expressing mRNA for all the cytokines investigated. Four membranes possessed positive cells for IL-6 and TNF, two contained cells expressing mRNA for IL-6 and IL-1, and two others exhibited cells expressing mRNA for TNF and IL-1. Five membranes contained IL-6 mRNA-positive cells only, whilst two exhibited cells expressing mRNA for IL-1, or TNF only. Conclusion The present findings indicate that cellular activation may occur during the development of PVR, and suggest that these cytokines may be locally produced by cells infiltrating epiretinal membranes. The presence of IL-1, IL-6 and TNF mRNA-positive cells within retinal membranes provides further evidence of a pathogenic role of these cytokines in proliferative vitreoretinopathy.     

Increased release of tenascin in tear fluid after photorefractive keratectomy

Background: Extracellular matrix protein tenascin (TN) is expressed in the anterior stroma during corneal wound healing. In this study we analysed TN release in tear fluid after photorefractive keratectomy (PRK). Methods: Tear fluid TN concentrations of ten PRK patients were measured with an immunoassay. Tear fluids were collected preoperatively and 1, 2 and 7 days after PRK. The tear fluid collection time and the volume of tears collected were registered. Because tear fluid flow was greatly increased postoperatively, tear fluid flow-corrected release (TN flux) was calculated. Results: The tear fluid flow was 4.50±0.94 l/min (mean±SEM) preoperatively, 55.48±16.70 l/min (P<0.01) on the 1st, 33.91±7.91 l/min (P<0.01) on the 2nd, and 13.79±5.49 l/min (P>0.05) on the 7th postoperative day. The preoperative TN concentration was 0.85±0.20 g/ml. On the 1st postoperative day it decreased to 0.37±0.17 g/ml (P>0.05), most likely due to the dilution effect caused by hypersecretion after PRK. The TN concentration was 0.67±0.12 g/ml (P>0.05) on the 2nd and 0.78±0.15 g/ml (P>0.05) on the 7th postoperative day. The preoperative TN flux was 5.23±1.88 ng/min. On the 1st and 2nd postoperative days the TN flux was 14.40±4.99 ng/min (P<0.05) and 22.66±6.I2 ng/min (P<0.05), respectively. On the 7th postoperative day a tendency towards decreased flux (14.00±6.02 ng/min, P>0.05) was observed. Conclusion: Although there is a minor decrease in TN concentration after PRK due to increased tear fluid flow, a significant increase in TN flux was observed. Complete reepithelialization of the ablated area was observed in all eyes at the follow-up visit on postoperative day 7.     

Course of the optic nerve fibers through the lamina cibrosa in human eyes

Background: This study investigated whether regional variations in the course of the optic nerve fibers through the lamina cribrosa may be one of the reasons why the local susceptibility for glaucomatous optic nerve fiber loss differs among the various regions of the optic disc. Methods: The study included 34 human eyes enucleated because of a malignant melanoma of the peripheral choroid without involvement of the anterior chamber angle or the optic nerve. Anterior-posterior sections through the pupil and the optic disc were histomorphometrically evaluated. In the central region and the peripheral part of the optic disc, we measured the thickness of the lamina cribrosa and the length of the lamina cribrosa channels through which the nerve fibers pass. Results: In the peripheral parts of the disc, compared with its central region, the lamina cribrosa was significantly thicker (P<0.0001, Wilcoxon test), the lamina cribrosa channels with the nerve fibers passing through were significantly longer (P<0.0001), and the ratio of length of the fiber channels to the thickness of the lamina cibrosa was significantly higher (P=0.0001). Conclusion: The lamina cribrosa is thicker and the course of the optic nerve fibers through the lamina cribrosa is more curvilinear in the disc pheriphery than in the disc center. These variations in the anatomy of the lamina cribrosa may be one of several factors influencing the regional susceptibility for glaucomatous optic nerve fiber loss within the optic nerve head.     

Variability of contour line alignment on sequential images with the Heidelberg Retina Tomograph

Background: The influence of the contour line alignment software algorithm on the variability of the Heidelberg Retina Tomograph (HRT) parameters remains unclear. Methods: Nine discrete topographic images were acquired with the HRT from the right eye in six healthy, emmetropic subjects. The variability of topometric data obtained from the same topographic image, analyzed within different samples of images, was evaluated. A total of four mean topographic images was computed for each subject from: all nine discrete images (A), the first six of those images (B), the last six of those nine images (C), and the first three combined with the last three images (D). A contour line was computed on the mean topographic image generated from the nine discrete topographic images (A). This contour line was then applied to the three other mean topographic images (B, C, and D), using the contour line alignment in the HRT software. Subsequently, the contour line on the mean topographic images was applied to each of the discrete members of the particular images subsets used to compute the mean topographic image, and the topometric data for these discrete topographic images was computed successively for each subset. Prior to processing each subset, the contour line on the discrete topographic images was deleted. This strategy provided a total of three analyses on each discrete topographic image: as a member of the nine images (mean topographic image A), and as a member of two subsets of images (mean topographic image B, C, and/or D). The coefficient of variation (100×SD/mean) of the topographic parameters within those three analyses was calculated for each discrete topographic image in each subject (intraimage coefficient of variation). In addition, a coefficient of variation between the nine discrete topographic images (interimage coefficient of variation) was calculated. Results: The intraimage and interimage variability for the various topographic parameters ranged between 0.03% and 3.10% and between 0.03% and 24.07% respectively. The intraimage coefficients of variation and interimage coefficients of variation correlated significant (r ²=0.77;P<0.0001). Conclusion: A high intraimage variability, i.e. a high variability in contour line alignment between sequential images, might be an important source of test re-test variability between sequential images.