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Biomedical subjects

M D de Smet

Publications and source records attributed to M D de Smet.

At least 19 recordsLinked to original sources

Added value of OCT in evaluating the presence of leakage in patients with age-related macular degeneration treated with PDT.

BACKGROUND: Evaluating the presence of leakage on fluorescein angiography (FA) in patients with age-related macular degeneration (AMD) retreated with photodynamic therapy (PDT) can be difficult. New diagnostic tools such as optical coherence tomography (OCT) might help to optimize PDT management. METHODS: Thirty AMD patients scheduled for regular follow-up FA in conjunction with PDT treatment were also scanned with OCT. Follow-up data at 9 months were retrieved from the patients' medical records. Inter-observer agreement [kappa coefficient] for the presence of leakage on FA, for OCT parameters for leakage, and agreement between FA and OCT evaluations were calculated. The indication for retreatment was evaluated using the leakage analysis based on FA alone, OCT alone, and both examinations combined, and compared to the actual follow-up of the patients at 9 months. RESULTS: Agreement between the two observers for the presence of leakage on FA was moderate (kappa=0.51). OCT agreement between the two observers for the presence of leakage was good (kappa=0.85). Agreement between FA and OCT for the presence of leakage was poor (kappa=0.16). Follow-up data at 9 months on all patients were analyzed. Seven out of 30 patients were not retreated at the time of examination, and four of these patients (57%) remained stable without further treatment. Twenty-three patients did receive a PDT treatment at the time of examination; and eight of these patients did not show leakage on OCT, and five of these patients (62%) remained stable without additional treatment. In contrast, only three out of 15 patients (20%) with leakage on both FA and OCT remained stable during this 9 month follow-up period. CONCLUSIONS: Inter-observer agreement for the presence of leakage was moderate for FA and good for OCT. There was considerable disagreement between leakage as judged by OCT and by FA. OCT could be of help in the decision regarding PDT retreatment. Assuming that 57% of the patients without leakage either on FA or OCT would remain stable without retreatment, the rate of probable ineffective retreatment could be reduced from 35% to 20%.

Aged↗

Single spot PDT in patients with circumscribed choroidal haemangioma and near normal visual acuity.

BACKGROUND: In circumscribed choroidal hemangiomas (CCH) a long observation period and decreased visual acuity before treatment are risk factors for poor visual outcome. Therefore, we studied the use of limited, single spot photodynamic therapy (PDT) with Visudyne for the timely treatment of CCH. METHODS: Six consecutive patients with CCH, and metamorphopsia but (near) normal visual acuity were treated with PDT, using a single spot covering only the most prominent part of the tumour, and a radiance exposure of 50 J/cm(2). Start of treatment was 6 min following a 1-min infusion with Visudyne (6 mg/m(2) BSA), using a diode laser (692 nm). RESULTS: In all patients, the metamorphopsia disappeared, the OCT images returned to a normal foveal contour, and visual acuity remained 20/20 or improved to 20/20. In five patients, the tumour became ultrasonographically undetectable; in three after one PDT session, in one patient after two and in another patient after three PDT sessions. The last patient had a residual tumour height of 1.2 mm, but no metamorphopsia, a normal foveal contour on OCT, and fluorescein angiography showed no residual leakage. CONCLUSION: The present series demonstrates that single spot PDT might be an effective treatment for CCH with a visual acuity > or =20/30, without serious side-effects during a follow-up of at least 18 months.

Adult↗

Precursor B lymphoblastic lymphoma of the orbit in a child: an unusual presentation of a non-Hodgkin lymphoma.

OBJECTIVE: The majority of ocular adnexal lymphomas are marginal zone lymphomas, which occur rarely in children. This case report describes a 6 years old child with a precursor B lymphoblastic lymphoma presenting in the ocular adnexa. The combination of multi-agent chemotherapy with adjuvant radiotherapy seems to be necessary in order to achieve a complete remission of this subtype of lymphoma's in ocular adnexa. DESIGN: Retrospective case study. METHOD: A review of the clinical, pathological, radiological findings and follow-up in a patient from the files available at our center, which were reviewed between the years 1974 and 2004.

Child↗

Influence of cataract on optical coherence tomography image quality and retinal thickness.

BACKGROUND: As optical coherence tomography (OCT) is widely used for diagnosis and monitoring of ocular pathology, especially in the elderly people, the influence of cataract on image quality and macular retinal thickness was studied. METHODS: In 29 patients scheduled for cataract surgery, preoperative and postoperative OCT scans were obtained. Cataracts were categorised as nuclear, posterior or cortical. Parameters for image quality (signal-to-noise ratio (SNR)) and signal strength and macular thickness were compared. A three-level expert grading scale was used to evaluate the discriminative abilities of SNR and signal strength. RESULTS: Nuclear cataracts (n = 12) provided better preoperative scans (higher SNR/signal strength) than posterior (n = 7) and cortical (n = 10) cataracts (p<0.004). Postoperatively SNR and signal strength increased significantly in all patients (p<0.001). The SNR was better at discriminating poor from acceptable and good scans than signal strength (area under the receiver operating curve: 0.879 and 0.810, respectively). Postoperative macular thickness overall showed a significant increase (p = 0.005), most evident in patients with posterior cataracts (p = 0.028). CONCLUSIONS: OCT imaging is influenced by cataract; image quality is reduced preoperatively and macular thickness measurements are slightly increased postoperatively. In individual patients, OCT scans remain reliable for gross clinical interpretation, even in the presence of cataract.

Aged↗

[News on therapies for uveitis].

The immunosuppression required for the treatment of uveitis can be achieved through conventional agents or through the use of specific modulators of inflammation. Whatever the choice, it is important to limit side effects: by restricting access to certain drugs in patients presenting a high risk of complications (tuberculosis screening before using Remicade), reducing side effects through preventive measures (use of alendronates during oral corticotherapy), or choosing a local delivery route (intraocular triamcinolone). Intraocular triamcinolone has certain beneficial characteristics such as high local dosage without systemic effect. However, it can cause a pressure rise in 10% to 20% of patients. It requires certain precautions when given to prevent development of a pseudo-endophthalmitis. Remicade is a novel synthetic immunosuppressant directed against TNF-alpha. This chimeric antibody can be useful in the treatment of severe uveitis that is unresponsive to conventional therapy. It is currently being tested in clinical trials in uveitis both in Europe and the USA.

Anti-Inflammatory Agents↗

The surgical management of chronic hypotony due to uveitis.

PURPOSE: Evaluate surgery in chronic hypotony secondary to uveitis. METHOD: Retrospective analysis of six patients operated for chronic hypotony (< or =5 mmHg) of at least 1 month's duration. Surgery involved removal of all traction and membranes on the ciliary processes. Use of oil was limited to patients with atrophic ciliary processes. RESULTS: The average postoperative follow-up was 24 months (12-43). The average pressure increase was 7 mmHg at 6 months. Four of six uveitis patients had significantly increased vision. CONCLUSION: Improved vision, and a sustained pressure rise are possible in hypotonous uveitis. The presence of ciliary processes is necessary. However, they do not need to be intact.

Adolescent↗

Evaluation of central serous retinopathy with en face optical coherence tomography.

BACKGROUND: The diagnosis of idiopathic central serous retinopathy (CSR) is usually based on biomicroscopy and fluorescein angiography (FA). The optical coherence tomography (OCT) ophthalmoscope produces en face OCT scans (OCT C-scans) and provides additional information not readily available by conventional imaging techniques. The authors describe the characteristic features observed in patients with a clinical diagnosis of CSR using the OCT ophthalmoscope. METHODS: 38 eyes with a clinical diagnosis of CSR, seen at the Academic Medical Centre (Amsterdam, Netherlands) and the New York Eye and Ear Infirmary (New York, USA) between August 2002 and March 2004, were evaluated with standard digital FA and scanned with the OCT ophthalmoscope. RESULTS: Nine of 38 eyes had no serous neurosensory detachment (inactive CSR) when scanned with the OCT ophthalmoscope. Characteristics for active CSR (n=29) were large neurosensory detachment (23/29), subretinal hyper-reflective depoits (20/29), and pigment epithelial detachment (15/29). One third of the patients, either active or inactive, had multiple small pigment epithelial detachments located both within and outside the neurosensory detachment. CONCLUSION: The OCT ophthalmoscope provides complementary morphological information on patients with CSR. The presence of more diffuse retinal pigment epithelium (RPE) changes lends further support to the concept that CSR is a diffuse rather than localised RPE anomaly.

Acute Disease↗

Longstanding symptomatic choroidal hemangioma managed with limited PDT as initial or salvage therapy.

PURPOSE: To describe the use of limited, low-irradiance, single-spot photodynamic therapy (PDT) with verteporfin for the treatment of symptomatic choroidal hemangiomas. METHODS: Thirteen consecutive patients with a circumscribed choroidal hemangioma were treated with limited PDT 6 min following a 1-min infusion with verteporfin (6 mg/m(2) body surface area), using a diode laser (692 nm) and a single spot large enough to cover only the most prominent part of the tumor. Exposure time was 166 s in the first three patients and 83 s in the last ten patients, resulting in a radiance exposure of respectively 100 and 50 J/cm(2). RESULTS: In all 11 not previously conventionally treated patients, visual acuity improved following PDT treatment. The two remaining patients with prior radiation treatment both reported widening of the visual field and sharper vision, but did not show an increase in ETDRS vision. In all but four patients the tumor became ultrasonographically undetectable by the first follow-up visit at 6 weeks, with only a slight irregularity at the level of the previous tumor remaining. In four patients the residual tumor was still detectable, and they received a second treatment, following which the tumor flattened completely. In all patients the retinal detachment disappeared. CONCLUSION: The present series demonstrates that even limited, low-irradiance, single-spot photodynamic therapy with verteporfin is an effective first-line treatment for choroidal hemangiomas.

Adult↗

[Intravitreal chemotherapy for intraocular lymphoma].

Primary CNS and intraocular non-Hodgkin's lymphoma is currently mostly treated with systemic chemotherapy. After initially successful tumor regression, recurrence is common and usually treated with radiotherapy. However, after good primary therapeutic response, new tumor growth is frequently observed. Because of actinic complications, radiotherapy can be applied only once. For an intraocular recurrence of primary CNS and intraocular lymphoma, intravitreal chemotherapy (0.4 mg methotrexate and 0.4 mg dexamethasone weekly for 4 weeks and once a month thereafter) can be performed. A few weeks after initiation, regression of intraocular tumors and eventually improvement of vision can be achieved. Eyes remained free of recurrence up to 2 years after initiation of intravitreal injections. Intravitreal chemotherapy is an effective treatment for ocular recurrence of primary CNS and intraocular lymphoma after systemic chemotherapy and radiotherapy.

Antimetabolites, Antineoplastic↗

[Eye complaints indicative of a tumor elsewhere in the body].

A variety of clinical presentations of malignant tumour metastases outside of the eye and orbit, were seen in four patients: a 52-year-old man who was scheduled to have a surgical removal of an oesophageal carcinoma and who presented with retinal detachment, a 58-year-old woman in whom retinopathy was the first sign of a cervical carcinoma (cancer-associated retinopathy), a 71-year-old man who had been treated for colon carcinoma and who presented with an orbital mass, and finally a 67-year-old woman with an orbital mass as the first sign of a Grawitz tumour. Metastasis should be considered in patients with a history of malignancy, who present with ophthalmologic complaints. Further it should be borne in mind that eye problems can be the first sign of oncological disease outside the eye.

Aged↗

[Two children with extrapulmonary symptoms due to tuberculosis].

Two patients came to their general practitioner for relatively minor problems: a 4-year-old boy came with a red eye and a 10-year-old girl with red foot soles. They came from Pakistan and Vietnam respectively. Their symptoms were due to tuberculosis, which diagnosis was established by Mantoux test and culture of a stomach aspirate. They were treated accordingly with isoniazid, rifampicin and pyrazinamide and with isoniazid, rifampicin and ethambutol respectively. These cases stress the importance of knowledge of the extrapulmonary manifestations of tuberculosis. As treatment exists and adequate treatment can diminish the reservoir of tuberculosis bacteria, early diagnosis can prevent the morbidity, spread and mortality of tuberculosis.

Antitubercular Agents↗

Regulation of ocular inflammation--what experimental and human studies have taught us.

Study of models of ocular autoimmunity and of autoimmune uveitis in humans has lead to a shift in the perceived nature of immune privilege from one based on anatomical isolation of the eye to a more dynamic, active process of immune tolerance. Using a variety of available models, the basis for this dynamic process of immune regulation is reviewed. The protective role of humoral immunity, the co-stimulatory function of B cells in EAU as well as the influence of cytokines within the inflammatory cascade are outlined. Modulation of the immune response and in particular the possible role of macrophages is explored. Within the current paradyme, a major effector cell is the CD4+ lymphocyte. Its maturation into a Th1 or Th2 phenotype process appears dependent on a number of exogenous factors, which while genetically determined can be manipulated prior to disease onset. Activation of CD4+ cells is dependent on presentation of immunoreactive peptide fragments. These fragments are well characterized in the Lewis rat for S-Ag and interphotoreceptor retinoid binding protein (IRBP). Mapping of the immunoreactivity to S-Ag has been recently completed in uveitis patients. An overlap with certain determinants identified in experimental models has been observed, in at least 2 disease entities. However, the response profile is not fixed in time and is subject to determinant spread. Future studies will be aimed at identifying with more detail immunologic triggers of inflammation in patients, and at better defining the interplay between effector and regulatory pathways both in the eye and in the systemic circulation.

Amino Acid Sequence↗

Circulating antibodies to inducible heat shock protein 70 in patients with uveitis.

Heat shock proteins with molecular weight 70 kDa (hsp70) are highly conserved immunogenic intracellular molecules. There are two main subtypes: one is expressed constitutively (hsc70), while the other is induced under stressful conditions (ihsp70). Using an ELISA directed against recombinant human ihsp70, antibody titers were determined in patients with defined ocular inflammatory conditions (Behçet's disease, Vogt-Koyanagi-Harada (VKH), pars planitis, and sarcoidosis) as well as in a group of age-matched normal volunteers. In comparison to healthy controls (n = 14, absorbance 0.269), levels were significantly elevated in Behçet's disease (n = 18; 0.412), sarcoidosis (n = 15; 0.432), and pars planitis (n = 13; 0.346), but not in VKH (n = 10; 0.263). A correlation was also noted for treatment versus no treatment in pars planitis (p = 0.028), but not in other inflammatory conditions. There was no correlation with the level of intraocular disease activity as defined by vitreous haze and vision drop. Since pars planitis is a purely ocular condition, circulating levels of ihsp antibodies likely reflect the extent of disease involvement within the eye.

Adolescent↗

Adenocarcinoma of the esophagus with choroidal metastasis.

In this report, a case is presented of an adenocarcinoma in a Barrett's esophagus metastatic to the choroid. A 54-year-old woman presented with a rapidly progressive decrease of vision in the right eye 8 months after intentionally curative esophagectomy for an adenocarcinoma. Fundoscopy, ultrasonography, and magnetic resonance imaging findings were suggestive of a metastasis. The patient received palliative external beam irradiation to the right eye for visual restoration, but she died before any beneficial effect was achieved.

Adenocarcinoma↗

Prevalence of subclinical anterior uveitis in adult patients with inflammatory bowel disease.

AIM: To assess the prevalence of subclinical anterior uveitis in adult patients with inflammatory bowel disease. METHODS: In 179 consecutive patients (96 with Crohn's disease, 55 with ulcerative colitis, and 28 with inflammatory bowel disease of undetermined nature) without previous or concurrent ocular complaints, quantitative flare measurements were obtained with the Kowa FC laser flare to detect the presence of subclinical uveitis. RESULTS: The mean flare value was 3.9 (SD 1.1) ph/ms in patients younger than 30 years of age, rising to 5.8 (2.5) ph/ms in those over 60 years of age. No measurement performed in this patient population fell outside the mean observed value plus or minus SD of the normal controls within the same age category. CONCLUSION: In an adult population of 179 consecutive patients with inflammatory bowel disease the presence of a form of subclinical uveitis, as described by Hofley et al in a group of juvenile patients, is highly unlikely.

Adult↗

Management of non Hodgkin's intraocular lymphoma with intravitreal methotrexate.

Intraocular non Hodgkin's lymphoma has traditionally been treated with radiotherapy or systemic chemotherapeutic agents. Unfortunately, radiotherapy rarely leads to a long term remission, and can only be safely administered once. Systemic chemotherapy has limited intraocular penetration. Intravitreal administered methotrexate is highly effective at inducing remission and is well tolerated. A case report is presented of a recurrent intraocular lymphoma following radiotherapy and systemic chemotherapy which responded to a combination of intravitreal methotrexate and dexamethasone. A response was seen within three weeks of treatment initiation. Toxicity was limited to the progression of a pre-existing cataract. Review of the literature shows that intravitreal methotrexate is well tolerated, with few acute complications. However, with monotherapy, local recurrences have been observed.

Aged↗

Human S-antigen determinant recognition in uveitis.

PURPOSE: Soluble antigen (S-Ag) is a member of the arrestin family of protein with which it shares a high level of homology. It is an immunologically privileged retinal antigen that can elicit experimental autoimmune uveitis (EAU) and is thought to be a target for ocular inflammatory diseases. This study was conducted to identify in humans, the immunogenic determinants of human S-Ag and to establish whether a specific response profile occurs in particular ocular inflammatory conditions. METHODS: Peripheral blood lymphocyte responses were measured against a panel of 40 overlapping synthetic peptides of human S-Ag in patients with chronic uveitis and compared with control subjects. Patients with Behçet disease, sarcoidosis, Vogt-Koyanagi-Harada, and sympathetic ophthalmia were tested. RESULTS: A limited number of immunodominant determinants were identified for Behçet disease and sarcoidosis. These were all located at sites of limited homology with other known arrestins. In addition, several individual patients had prominent proliferative responses to multiple determinants well above that of control subjects. This determinant spread was observed in all disease entities except sympathetic ophthalmia, which did not show any immunoreactivity to S-Ag. Significant response shifts were also noted over time in two patients. CONCLUSIONS: The results indicate that there are specific immunodominant determinants to human S-Ag in patients with certain forms of uveitis. However, in individual patients, response is not limited to these determinants. In the chronic stage of disease, response is spread over many determinants.

Adult↗

Prospective determination of T-cell responses to S-antigen in Behçet's disease patients and controls.

PURPOSE: To prospectively determine, using two different assays, the lymphocyte proliferative response to a retinal autoantigen (S-antigen) in patients with Behçet's disease who are under treatment for ocular inflammation. METHODS: Patients were evaluated at each visit for signs of ocular inflammation. Peripheral blood leukocytes were harvested and cultured in the presence of bovine S-antigen in a standard culture assay, as well as by limiting dilution using multiple short-term T-cell lines. RESULTS: Five patients were observed for 2 to 10 months. During follow-up, three patients had episodes of ocular inflammation. No consistent change in proliferative response was observed in standard proliferation assays. However, an increase in established T-cell lines was correlated to the presence of ocular inflammation in all three patients. Ocular activity was associated with an increase of 9- to 30-fold in the frequency of short-term T-cell lines. This increase returned to baseline within 1 to 3 months. CONCLUSIONS: An increase in S-antigen-responsive lymphocytes is found in the peripheral blood of patients with Behçet's disease during episodes of ocular inflammation. This increase cannot be measured using standard proliferation assays but requires the use of techniques exploiting the principles of limiting dilution analysis.

Adult↗