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Marc D de Smet

Publications and source records attributed to Marc D de Smet.

16 recordsLinked to original sources

Recent developments in optical coherence tomography for imaging the retina.

Optical coherence tomography (OCT) was introduced in ophthalmology a decade ago. Within a few years in vivo imaging of the healthy retina and optic nerve head and of retinal diseases was a fact. In particular the ease with which these images can be acquired considerably changed the diagnostic strategy used by ophthalmologists. The OCT technique currently available in clinical practice is referred to as time-domain OCT, because the depth information of the retina is acquired as a sequence of samples, over time. This can be done either in longitudinal cross-sections perpendicular to, or in the coronal plane parallel to the retinal surface. Only recently, major advances have been made as to image resolution with the introduction of ultrahigh resolution OCT and in imaging speed, signal-to-noise ratio and sensitivity with the introduction of spectral-domain OCT. Functional OCT is the next frontier in OCT imaging. For example, polarization-sensitive OCT uses the birefringent characteristics of the retinal nerve fibre layer to better assess its thickness. Blood flow information from retinal vessels as well as the oxygenation state of retinal tissue can be extracted from the OCT signal. Very promising are the developments in contrast-enhanced molecular optical imaging, for example with the use of scattering tuneable nanoparticles targeted at specific tissue or cell structures. This review will provide an overview of these most recent developments in the field of OCT imaging focussing on applications for the retina.

Humans↗

Association of connective tissue growth factor with fibrosis in vitreoretinal disorders in the human eye.

OBJECTIVE: To investigate the expression of the profibrotic connective tissue growth factor (CTGF) in relation to severity of intraocular fibrosis and neovascularization in human vitreoretinal disorders for the identification of potential therapeutic targets to prevent fibrosis. METHODS: Concentrations of CTGF were measured by enzyme-linked immunosorbent assay in 119 vitreous samples from patients with proliferative diabetic retinopathy, proliferative vitreoretinopathy, epiretinal membrane, and macular hole. Clinical data, including degree of intraocular fibrosis and neovascularization, were collected using standardized forms. RESULTS: Multifactorial analysis revealed that only CTGF levels correlated highly significantly with degree of fibrosis in the various vitreoretinal disorders studied (P<.001; R2= 47.7%). Likewise, variation in degree of fibrosis was best predicted by CTGF levels (P<.001). CONCLUSION: The strong correlation between CTGF levels and degree of fibrosis in vitreoretinal disorders suggests that CTGF is an important factor in ocular fibrosis, similar to its role in pathologic fibrosis in other organs. CLINICAL RELEVANCE: Connective tissue growth factor may be a therapeutic target for prevention of sight-threatening vitreoretinal scarring in the eye.

Connective Tissue Growth Factor↗

Combined en-face optical coherence tomography and confocal ophthalmoscopy findings in active multifocal and serpiginous chorioretinitis.

PURPOSE: To describe retinal changes in active multifocal and serpiginous chorioretinitis seen with en-face optical coherence tomography (OCT). DESIGN: Observational case report. METHODS: Two patients, presenting with active multifocal chorioretinitis (MFC) and serpiginous chorioretinitis (SC), respectively, were scanned with a prototype en face OCT ophthalmoscope. RESULTS: The OCT scan in the patient with the active MFC lesion showed a transretinal hyperreflectivity at the site of lesion. The OCT scan in the patient with the active SC lesion showed hyper-reflectivity in the outer retina at the site of the lesion. CONCLUSIONS: OCT allows for better evaluation of intraretinal changes in patients with white dot syndromes. In these two cases, OCT showed different morphologic changes in active lesions. OCT may be helpful in identifying the location of involvement in various white dot syndromes. This may have prognostic and therapeutic significance.

Adult↗

Imaging the retina by en face optical coherence tomography.

PURPOSE: To present the possibilities of a new system that combines optical coherence tomography (OCT) and confocal ophthalmoscopy, producing en face OCT images in patients with retinal diseases. METHODS: A prototype OCT Ophthalmoscope (OTI, Toronto, Canada) was used to scan patients with retinal conditions. The system uses a super luminescent diode (lambda = 820 nm; Deltalambda = 20 nm) and currently scans at a rate of 2 frames per second. In each frame, the OCT Ophthalmoscope simultaneously produces a transversal OCT scan and a confocal image in the X/Y plane. Both images correspond pixel to pixel. RESULTS: Between January 2002 and August 2003, >800 patients with various retinal diseases were scanned with the OCT Ophthalmoscope. Illustrative cases with regularly seen macular diseases are presented, such as macular hole and central serous retinopathy. CONCLUSION: Current difficulties as well as future possibilities of this new en face OCT ophthalmoscope are discussed. By presenting normal and pathologic transversal OCT images made by a prototype OCT Ophthalmoscope, we show that it can provide information not available using conventional OCT imaging.

Humans↗

Does cerebral monitoring improve ophthalmic surgical operating conditions during propofol-induced sedation?

Sudden movements from over-sedation during ophthalmic surgery can be detrimental to the eye. Bispectral index (BIS) and middle-latency auditory-evoked potentials (Alaris AEP index, AAI) were reported to be accurate indicators for the level of sedation and loss of consciousness. We assessed these monitors during sedation with special emphasis on preventing over-sedation. One-hundred patients scheduled for elective eye surgery were sedated with target-controlled propofol infusion and randomly allocated to BIS-guided, AAI-guided, BIS/AAI-guided, or clinically guided groups (n = 25 each). The initial target concentration was 0.5 microg x mL(-1) in patients >70 yr and 1.0 microg x mL(-1) in all other patients. The concentration was increased every 3 min by 0.1 or 0.2 microg x mL(-1), respectively until the patient had reached a BIS value of 75 (range 70-90) or an AAI of 40 (range 35-60). The surgeon who was blinded to group allocation assessed treatment quality after the procedure. Sedation was converted into general anesthesia in four patients because of excessive head movements. BIS was out of range 7% of the time vs 58% for AAI. No significant differences in treatment quality were observed among the four groups. We conclude that propofol sedation, guided by BIS or AAI monitoring, did not enhance ophthalmic surgical operating conditions over sedation guided by clinical observation only.

Adolescent↗

Pooled efficacy results from two multinational randomized controlled clinical trials of a single intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage.

PURPOSE: To evaluate the efficacy of intravitreous ovine hyaluronidase for the management of vitreous hemorrhage. DESIGN: Two prospective, randomized, placebo-controlled, double-masked studies. Safety data are presented in a companion article in The Journal. METHODS: Eligible patients with vitreous hemorrhage > or = 1 month duration; severe at entry with best corrected visual acuity (BCVA) worse than 20/200 were randomized to 55 IU or 75 IU ovine hyaluronidase or saline. Primary efficacy (clearance of hemorrhage sufficient to see the underlying pathology and completion of treatment when indicated) was measured at months 1, 2, and 3. Key secondary endpoints were: > or = 3-line improvement in BCVA; hemorrhage density reduction; and therapeutic utility assessment. RESULTS: The intent-to-treat population for common dose groups (55 IU, 75 IU, saline) consisted of 1125 patients. At baseline, 76.3% had diabetes, 90.4% were not able to read any letters on the eye chart, and mean hemorrhage duration was 120 days. Statistical significance was reached in the 55 IU dose group by months 1 and 2 for the primary efficacy endpoint based on an adjusted P-value. By months 1, 2, and 3, 13.2%, 25.5%, and 32.9% of patients (55 IU) reached primary efficacy compared with 5.5%, 16.2%, and 25.6% of saline-treated patients (P < .001; P = .002; P = .025, respectively). Key secondary endpoints confirmed the treatment effect at both doses and all timepoints (P < or = .01). CONCLUSIONS: Fifty-five IU ovine hyaluronidase showed statistically significant efficacy as early as months 1 and 2. These results were supported by outcomes for three key secondary endpoints. These results suggest a therapeutic utility of ovine hyaluronidase in the management of vitreous hemorrhage.

Diabetes Mellitus, Type 1↗

VAMP5 and VAMP8 are most likely not involved in primary open-angle glaucoma.

PURPOSE: To select and characterize novel POAG disease genes. On the basis of genetic position (GLC1B), expression in the optic nerve, and biochemical function (targeted membrane transport processes), we selected the human VAMP5 and VAMP8 (encoding vesicle-associated membrane proteins 5 and 8) as potential candidate disease genes for POAG. We subsequently analyzed whether or not sequence changes in VAMP5 or VAMP8 were implicated in POAG. METHODS: Genomic DNA samples from 90 POAG cases and 60 controls were screened by denaturing high performance liquid chromatography of fragments amplified by the polymerase chain reaction. Direct sequencing identified nucleotide changes. RESULTS: No nonsynonymous rare sequence variants were found in VAMP5 or VAMP8. In VAMP5, three previously identified and five new single nucleotide polymorphisms (SNPs) were found. In VAMP8, four known and two new SNPs were detected. All new SNPs did not appear to change gene function or alter gene splicing. No significant differences were found between the allele frequencies in POAG cases and controls. CONCLUSIONS: Our findings indicate that VAMP5 and VAMP8 are not involved in POAG in the Dutch population.

Chromatography, High Pressure Liquid↗

Overlay of conventional angiographic and en-face OCT images enhances their interpretation.

BACKGROUND: Combining characteristic morphological and functional information in one image increases pathophysiologic understanding as well as diagnostic accuracy in most clinical settings. En-face optical coherence tomography (OCT) provides a high resolution, transversal OCT image of the macular area combined with a confocal image of the same area (OCT C-scans). Creating an overlay image of a conventional angiographic image onto an OCT image, using the confocal part to facilitate transformation, combines structural and functional information of the retinal area of interest. This paper describes the construction of such overlay images and their aid in improving the interpretation of OCT C-scans. METHODS: In various patients, en-face OCT C-scans (made with a prototype OCT-Ophthalmoscope (OTI, Canada) in use at the Department of Ophthalmology (Academic Medical Centre, Amsterdam, The Netherlands)) and conventional fluorescein angiography (FA) were performed. ImagePro, with a custom made plug-in, was used to make an overlay-image. The confocal part of the OCT C-scan was used to spatially transform the FA image onto the OCT C-scan, using the vascular arcades as a reference. To facilitate visualization the transformed angiographic image and the OCT C-scan were combined in an RGB image. RESULTS: The confocal part of the OCT C-scan could easily be fused with angiographic images. Overlay showed a direct correspondence between retinal thickening and FA leakage in Birdshot retinochoroiditis, localized the subretinal neovascular membrane and correlated anatomic and vascular leakage features in myopia, and showed the extent of retinal and pigment epithelial detachment in retinal angiomatous proliferation as FA leakage was subject to blocked fluorescence. The overlay mode provided additional insight not readily available in either mode alone. CONCLUSION: Combining conventional angiographic images and en-face OCT C-scans assists in the interpretation of both imaging modalities. By combining the physiopathological information in the angiograms with the structural information in the OCT scan, zones of leakage can be correlated to structural changes in the retina or pigment epithelium. This strategy could be used in the evaluation and monitoring of patients with complex central macular pathology.

Choroid Diseases↗

Safety results of two phase III trials of an intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage.

PURPOSE: To evaluate the safety of intravitreous ovine hyaluronidase for the management of vitreous hemorrhage. DESIGN: Two prospective, randomized, placebo-controlled, double-masked studies. Pooled efficacy data are presented in a companion article in this issue of The Journal. METHODS: Subjects with vitreous hemorrhage > or = 1 month, severe at entry and best corrected visual acuity (BCVA) worse than 20/200 in the study eye were randomized to 7.5 IU, 55 IU, 75 IU ovine hyaluronidase, saline, or no injection. Assessments occurred on day 1, week 1, months 1, 2, 3, 6, and then every 6 months for as long as 32 months. Assessments included history, ocular symptoms, adverse events, BCVA, intraocular pressure, external eye examination, slit-lamp biomicroscopy, fundus examination, B-scan ultrasonography, and fundus photography. RESULTS: Of 1362 subjects in the safety population, 1344 received hyaluronidase or saline and 18 no treatment. Iritis was the most common ocular adverse event, occurring in 33.3%, 62.1%, 58.9%, and 62.1% of saline, 7.5 IU, 55 IU, and 75 IU-treated subjects. In eyes with more than mild iritis, a dose response was observed: 8.9%, 20.2%, 33.7%, and 39.7% of saline, 7.5 IU, 55 IU, and 75 IU-treated subjects, respectively, were noted to have moderate or severe iritis. Retinal detachments (RDs) were reported in 9.5% of study eyes: 26 (6.9%), 22 (11.1%), 35 (9.3%), and 45 (11.5%) in the saline, 7.5 IU, 55 IU, and 75 IU-treated subjects. Overall, 1.8% of study eyes had rhegmatogenous RD: 1.1%, 2.5%, 1.6%, and 2.3% of saline, 7.5, 55, and 75 IU treated subjects. Cataracts occurred similarly across treatment groups. No injection-related infectious endophthalmitis was reported. CONCLUSIONS: No serious safety issues were reported after a single intravitreous injection of ovine hyaluronidase. RD incidence was not statistically different between groups. Iritis manifesting as an acute self limited inflammation was the most common adverse event, occurred in a dose response fashion, but was not noted to result in a serious adverse event in any hyaluronidase treated eye.

Aged↗

Artisan lens implantation to correct aphakia after vitrectomy for retained nuclear lens fragments.

PURPOSE: To report the results of pars plana vitrectomy (PPV) for retained lens fragments with implantation of an Artisan intraocular lens (IOL) (Ophtec) to correct aphakia. SETTING: University-based referral center. METHODS: In this retrospective case-controlled study, patients who had had a PPV to remove dislocated lens fragments and implantation of an Artisan IOL for pseudophakic correction during initial cataract surgery or PPV were reviewed. RESULTS: Thirteen patients were identified. The preoperative visual acuity was better than 20/200 in 5 patients and the intraocular pressure (IOP) was higher than 21 mm Hg in 8 patients; 3 patients had normal corneas. In 4 patients, an Artisan IOL was implanted during cataract surgery. Postoperative complications included recurrent erosion (1 eye), premacular fibrosis (2 eyes), and a retinal tear (1 eye). Elevation of the IOP occurred in 2 patients and was controllable with medication. Pupillary block developed in 1 patient and persistent cystoid macular edema in another. All but 2 patients gained more than 2 lines of visual acuity postoperatively, and all corneas remained clear during the follow-up (mean 28.9 months; range 2.5 to 69.0 months). CONCLUSIONS: After the removal of dislocated lens fragments with a PPV, Artisan IOL implantation in aphakic patients without capsule support led to few complications and good visual acuity. Placement of an Artisan IOL requires fewer manipulations than transscleral suture fixation of a posterior chamber IOL.

Aged↗

Microdissection combined with the polymerase chain reaction to identify potentiating viral co-infection in patients with HIV/AIDS with ocular infection.

BACKGROUND: In the presence of several coexisting infections, superimposed tissue necrosis or tissue metaplasia, it may be difficult to recognize standard histologic morphology on hematoxylin-eosin slides. Tissue microdissection combined with the polymerase chain reaction (PCR-MD) offers the advantages of high specificity and relative speed. The objective of this study was to describe the use of PCR-MD in identifying potentiating viral co-infection in patients with HIV/AIDS with retinitis and choroiditis. METHODS: Eyes from two patients with HIV/AIDS with several ocular infections were studied by a variety of techniques, including standard histologic examination, immunochemistry, electron microscopy and in situ hybridization. PCR-MD was used to identify coexisting viral infections. RESULTS: Histologic examination showed cytomegalovirus retinitis in both cases. Use of PCR-MD allowed the identification of Epstein-Barr virus within a zone of fulminant varicella-zoster virus retinitis in one patient. PCR-MD confirmed the presence of human herpesvirus 8 in the second patient, who had ocular lymphoma. INTERPRETATION: PCR-MD can be used to demonstrate coexisting viral infection in ocular specimens from patients with unusually fulminant courses. Co-infections may contribute to the observed clinical course and should be considered in patients with rapid progression or unusual presentation.

Adult↗

The ocular humoral immune response in health and disease.

This review focuses on several aspects of humoral immunologic defence of the ocular surface and intraocular compartment. Secretory IgA (sIgA) is a major component of lacrimal fluid and contributes to the first line of defence against infection of the ocular surface. Recent findings show that part of the lacrimal gland (LG) IgA repertoire consists of so-called natural IgA antibodies. How B cells responsible for these natural IgA antibodies are distributed to effector mucosal sites like the LG is not known. Extensive data are now available on the regionalization of mucosal IgA responses in murine gut, involving peritoneal B cells, the prototypic natural antibody producing cells. By comparing elaborate experiments done in mice with the much less extensive data on the LG, it becomes clear that this gland is a unique, but poorly investigated effector organ of the mucosal immune system. In addition to the humoral immune response at the surface of the eye, the production of antibodies within the ocular compartment also has several fascinating features. The detection of pathogen-specific antibodies in intraocular fluid (IOF) of uveitis patients is accepted as a diagnostic tool, but the specificity of these intraocular antibodies was not investigated in much detail. Recent data however, demonstrate that even antibodies recognizing the same antigen in both serum and IOF still differ in the epitopes they recognize. This reveals that the intraocular compartment largely determines its own antibody profile in the defence against intra-ocular pathogens. Several models as to how an exclusive intra-ocular B cell repertoire may be generated are presented.

Animals↗

Standard achromatic perimetry, short wavelength automated perimetry, and frequency doubling technology for detection of glaucoma damage.

OBJECTIVE: Reevaluation of the relationship between short wavelength automated perimetry (SWAP), standard achromatic perimetry (SAP), and frequency doubling technology (FDT) in glaucoma and ocular hypertensive patients and in glaucoma suspects. DESIGN: Prospective comparative observational study. PARTICIPANTS: Four age-matched groups were evaluated (42 patients with early to moderate glaucoma, 34 ocular hypertensives, 22 glaucoma suspects, and 25 normal controls) using SAP, SWAP, and FDT. INTERVENTION: All participants underwent full clinical ophthalmologic evaluation followed by SWAP, SAP, and FDT perimetry within a period of not more than 3 months. Mean defect (MD), pattern standard deviation (PSD), visual field (VF) indices, and the percentage of depressed visual field points with P value <5% and <1% in the pattern deviation plot were evaluated. MAIN OUTCOME MEASURES: For each of the four study groups, the MD, PSD, and the percentage of abnormal points significantly depressed <5% and <1% were compared for the three VF testing modalities. RESULTS: In the glaucoma group, the mean percentage of the total number of abnormal points in SWAP was significantly less than abnormal points in SAP and FDT, both for 5% (P values were 0.0001 and 0.0001, respectively) and 1% (P values were 0.0001 and 0.0001, respectively). The same applied to the ocular hypertensives group. However, in the suspects group, no significant difference was detected. In normal controls, the abnormal points in SWAP were significantly lower than those in SAP for 5% (P value was 0.01) and 1% (P value was 0.05). FDT detected significantly larger defects (percentage of points <5%) than SAP in ocular hypertensives and suspects (P values were 0.01 and 0.004, respectively). CONCLUSIONS: SWAP in its existing condition is markedly less efficient than either SAP or FDT in detecting VF defects, especially in glaucoma patients and ocular hypertensives (defects detected with SWAP are less than both SAP and FDT). Defects detected with FDT are equivalent to SAP and sometimes larger, especially in ocular hypertensives and glaucoma suspects; this makes it a useful tool for picking up early glaucomatous defects in populations at risk.

Adult↗

Management of retinal detachments in pseudophakic patients with Artisan lenses.

PURPOSE: To report the management and outcomes of retinal detachment repair in patients with Artisan intraocular lenses (IOLs) used for pseudophakic correction. SETTING: Two university-based referral centers.In this retrospective case-control study, all cases of retinal detachments in patients with an Artisan IOL used for pseudophakic correction were reviewed over 5 years at 2 university clinics. RESULTS: Of the 20 patients identified, all had a detachment in 2 or more quadrants. A retinal tear was identified in 19 patients preoperatively. Thirteen patients had a standard buckling procedure, 3 with the addition of gas; 3 required a pars plana vitrectomy; and 2 were treated with pneumatic retinopexy alone. Reattachment was achieved with 1 procedure in 11 patients, with 2 procedures in 5 patients, and with 3 procedures in 3 patients; reattachment could not be achieved in 2 cases. Anterior displacement of the lens was noted when gas tamponade was used. When the displacement was significant, sodium hyaluronate 1% (Healon was used to prevent corneal endothelial touch. CONCLUSIONS: In most cases, the Artisan lens did not significantly limit peripheral retinal visibility. Standard buckling procedures were generally successful. Given the limited support provided by the iris, the presence of gas in the vitreous cavity can lead to anterior displacement of the lens. Corneal endothelial touch can be prevented by the use of Healon, which is sufficient if short-term gas tamponade is used.

Adult↗

Amino acid residue 67 (isoleucine) of HLA-DRB is associated with POHS.

PURPOSE: To investigate whether presumed ocular histoplasmosis syndrome (POHS) in The Netherlands is associated with HLA-DR2 and HLA-B7, as previously shown in the United States. METHODS: Twenty-four Dutch patients with POHS were included in this study. DNA isolated from peripheral blood leukocytes was typed for HLA by a sequence-based method. Associations were statistically determined. The frequencies of HLA alleles in bone marrow of donors listed on the European donor registry was used to represent the distribution in the normal population. Patients were included in the study only when no cells were present in the vitreous at any time and when fundus photographs fit the diagnosis made according to the following criteria: presence of peripapillary atrophy, presence of punched out chorioretinal lesions (histospots), and presence of a submacular scar. After the fundus photographs were judged, the patients were divided into two groups. Group1 contained patients who met all three diagnostic criteria (complete POHS), and group 2 contained patients who met one or two of the criteria (incomplete POHS). RESULTS: Group 1 consisted of 14 patients and group 2 of 10 patients. An association between POHS and HLA-DR2 and -B7 was present, compared with the normal Dutch control subjects. Although significant, the association between the frequency of HLA-DR2 and -B7 of all patients with POHS was less striking than the findings in patients with POHS in the United States. The association with DR2 in patients with incomplete POHS (group 2) was significantly different from that in the group with complete POHS (group 1). According to the defined criteria the association of POHS with HLA-B7 and -DR2 was confined to the incomplete POHS group and was not found in the complete POHS group. Furthermore, analysis of DR at the amino acid level, rather than at the allele level (DR2) showed that amino acid 67 of the DRB1 alleles had the most significant HLA association with POHS, independent of the two groups. CONCLUSIONS: POHS in Dutch patients was associated with HLA-B7 and -DR2, but more striking was the presence of isoleucine at position 67 of the HLA-DR molecule.

Alleles↗