Perspectives of Patients and Professionals on Implementing a Computer Adaptive Vision-Related Quality of Life Outcome (CAT-EyeQ) in Clinical Practice.

Purpose: The CAT-EyeQ is a computer adaptive test (CAT) which measures vision-related quality of life in patients having exudative retinal diseases. The aim of this study is to investigate the usability of the CAT-EyeQ in clinical practice and identify potential barriers and facilitators for implementation (problem analysis). Methods: Patients and health care professionals participated in the study regarding the usability of the CAT-EyeQ, and clinic managers and health care professionals were included in the problem analysis for implementation. In total, we conducted 18 semi-structured interviews. The Consolidated Framework for Implementation Research (CFIR) was used to develop the interview guides and to structure results. Results: Six themes were derived from the usability study and problem analysis: (1) quality of the CAT-EyeQ and the applicability to patients' needs and preferences, (2) embedding the CAT-EyeQ in current practice, (3) implementation climate of the eye hospitals, (4) attitude of professionals, (5) engaging and encouraging professionals, and (6) integration of the CAT-EyeQ in health care - needs after piloting. Conclusions: Patients and professionals mentioned that the CAT-EyeQ improved insight into the impact of eye diseases on a patient's daily life, it allowed for more attention on the patient perspective and the structured measurement of vision-related quality of life. The main perceived barriers mentioned by professionals for using the CAT-EyeQ were lack of time and the integration of the patient-reported outcome measure (PROM) results within the electronic patient record (EPR). Translational Relevance: The CAT-EyeQ, accompanied by an overview of stakeholder perspectives resulting from this implementation study, can now be used in clinical practice.

Diagnosing and monitoring the characteristics of Acanthamoeba keratitis using slit scanning and laser scanning in vivo confocal microscopy.

INTRODUCTION: Acanthamoeba keratitis (AK) is a serious and potentially blinding ocular infection caused by the free-living amoeba, Acanthamoeba. In vivo confocal microscopy (IVCM) is a non-invasive device which has been proven of great use to diagnose Acanthamoeba infections immediately. The aim of this review was to establish different patterns and signs of AK that appear on the IVCM both before and after treatment. METHODS: A systematic review of the literature from 1974 until September 2021 was performed using Embase and PubMed, following The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Twenty different signs of AK were observed using IVCM. The included studies used vastly different criteria to diagnose infections, ranging from just 1 to 13 of the signs, demonstrating the current lack of a standardised diagnosis of this infection using the IVCM. The appearance of double wall cysts, trophozoites, signet rings, target signs and clusters were shown to be pathognomonic to AK infections. Bright spots located in the corneal epithelium were demonstrated as non-reliable predictors of AK. The presence of cysts in clusters and single file can predict the need for corneal transplantation. The morphological changes in cysts using the IVCM following treatment were described as breaking down to hollow forms and occasionally surrounded by black cavities. Using this information, a visual guideline for identifying AK signs in diagnosis and follow-up using IVCM was created. CONCLUSION: Increased awareness of the different signs and patterns of AK that appear on the IVCM is crucial in order to correctly identify an infection and increase the potential of this device. Our guidelines presented here can be used, but further studies are needed in order to determine the relationship and aetiology of these signs and cellular changes on the IVCM both before and after anti-amoeba treatment.

Calibration of the Dutch EyeQ to Measure Vision Related Quality of Life in Patients With Exudative Retinal Diseases.

Purpose: This study aims to develop an item-bank to measure vision-related quality of life (Vr-QoL) and subsequently calibrate this set of items. Methods: Three Vr-QoL instruments were searched for suitable items to be added in the EyeQ. Patients who received antivascular endothelial growth factor treatment for various retinal diseases involving macular edema were included in the study and completed the 47-item EyeQ. Item response theory (IRT) was used to calibrate the EyeQ items, which was performed multiple times in subsets as a novel approach, containing 80% of the data. Differential item functioning (DIF) was evaluated for various variables. Results: Responses of 704 patients were used in analysis. One item violated the local independence IRT-assumption and showed a high percentage of missing values, after which this item was deleted from the item-bank. The data of the five subsets fitted the graded response model adequately, and no DIF was detected for items between subsets, after which mean item parameters were calculated. Item fit statistics were found to be good. DIF was detected for gender, age, and administration mode by the patient (independently vs. with help), this involved three items, which all showed negligible impact on total scores. Conclusions: Because of separate calibrations of the EyeQ in multiple subsets, a high robustness of item parameters is expected. Translational Relevance: The calibrated EyeQ can now be used for the assessment of Vr-QoL in patients suffering from exudative retinal diseases and is promising for use as a computer adaptive test.

Translation and content validity of the Dutch Impact of Vision Impairment questionnaire assessed by Three-Step Test-Interviewing.

BACKGROUND: Patients suffering from exsudative retinal diseases may experience severe central vision loss and this might have impact on their daily activities and quality of life. To measure the disabilities these patients may have, the use of the Impact of Vision Impairment Profile questionnaire is recommended. The aim of this study was to translate the original English 28-item Impact of Vision Impairment Profile (IVI) into the Dutch language and evaluate its comprehensibility, comprehensiveness and relevance as evidence of content validity. The translation process was performed using standardized methods. Content validity was assessed by cognitive debriefing using a Three-Step Test-Interview (TSTI) method for participants diagnosed with exudative retinal diseases. Step 1 and 2 focused on assessment of comprehensibility of items, step 3 on comprehensiveness and relevance. Audio-recorded qualitative data was analyzed using Atlas.ti. Data regarding comprehensibility problems was further categorized into item-specific problems and general problems. RESULTS: Few minor discrepancies in wording were found after translation. After conducting 12 cognitive interviews, data saturation was reached. All participants reported comprehensibility problems resulting from specific items, these were; sentence structure, vocabulary and formulation, influence of conditions or composite items and influence of comorbid disorders. Several general comprehensibility problems resulting from instructions or response categories were detected. The main general comprehensibility problem resulted from the layout of the Dutch-IVI. Most participants considered the included items as relevant and indicated that they covered the problems that occur due to vision impairment. CONCLUSIONS: Minor problems in the Dutch translation were detected and adjusted. The layout and instructions of the Dutch-IVI resulted in some comprehensibility problems. The Dutch-IVI appeared to be at risk of being interpreted as a generic patient reported outcome measure, instead of a disease-specific instrument, mainly due to the influence of co-morbidities. Adaptations should improve validity and reliability of the Dutch-IVI, however, cross-cultural comparisons may be at stake.

Microvascular changes of the retina in ankylosing spondylitis, and the association with cardiovascular disease - the eye for a heart study.

OBJECTIVE: Ankylosing spondylitis (AS) is associated with an increased risk of cardiovascular disease (CVD). Microvasculature changes can precede overt CVD, but have been studied poorly in AS. The retinal vasculature is easily accessible and changes are associated with CVD (e.g. arteriolar narrowing, venular widening, loss of tortuosity). This proof of concept study compared the retinal microvasculature of AS patients with healthy controls, and the influence of gender. METHODS: Cross-sectional case-control study comparing AS patients with healthy controls. Main inclusion criteria were: age 50-75 years, no diabetes mellitus and, for AS, fulfillment of the modified New York criteria. All subjects underwent fundus photography, analyzed with Singapore I Vessel Assessment software, and Optical Coherence Tomography Angiography (OCTA). Subjects were compared with generalized estimating equations (GEE). Multivariable analyses were adjusted for demographics and cardiovascular risk, and stratified for gender. RESULTS: Fifty-nine AS patients and 105 controls were included (50% women). Controls were significantly older than patients (68 versus 60, p<0.01), but did not differ in cardiovascular profile. Patients had a lower retinal arteriolar tortuosity (ß Ì¶-0.1, 95%CI [-0.2; -0.01], p = 0.02), and higher vessel density (ß 0.5, 95% CI [0.1; 0.9], p = 0.02). In addition, male AS patients showed a lower arteriovenular ratio compared to male controls (ß -0.03, p = 0.04, 95%CI [-0.05; -0.001]). There were no differences found between women with and without AS. CONCLUSION: This study detected several retinal microvascular changes, in AS patients compared to controls, which have been associated with CVD. Retinal imaging might be an interesting tool for future CVD screening.

Comparing the Effectiveness of Bevacizumab to Ranibizumab in Patients with Exudative Age-Related Macular Degeneration. The BRAMD Study.

PURPOSE: To compare the effectiveness of bevacizumab and ranibizumab in the treatment of exudative age-related macular degeneration (AMD). DESIGN: Multicentre, randomized, controlled, double-masked clinical trial in 327 patients. The non-inferiority margin was 4 letters. PATIENTS: Patients ≥ 60 years of age with primary or recurrent sub- or juxtafoveal choroidal neovascularization (CNV) secondary to AMD with a total area of CNV < 12 disc areas and a best corrected visual acuity (BCVA) score between 20 and 78 letters on an EDTRS like chart in the study eye. METHODS: Monthly intravitreal injections with 1.25 mg bevacizumab or 0.5 mg ranibizumab were given during one year. Intention to treat with last observation carried forward analysis was performed. MAIN OUTCOME MEASURES: Primary outcome was the change in BCVA in the study eye from baseline to 12 months. RESULTS: The mean gain in BCVA was 5.1 (±14.1) letters in the bevacizumab group (n = 161) and 6.4 (±12.2) letters in the ranibizumab group (n = 166) (p = 0.37). The lower limit of the 95% confidence interval of the difference in BCVA gain was 3.72. The response to bevacizumab was more varied; 24% of patients showed a gain of ≥15 letters, 11% a loss of ≥15 letters and 65% a gain or loss < 15 letters compared to 19%, 5% and 76% respectively for ranibizumab (p = 0.038). No significant differences in absolute CRT and CRT change (p = 0.13) or in the presence of subretinal or intraretinal fluid (p = 0.14 and 0.10, respectively) were observed. However, the presence of any fluid on SD-OCT (subretinal and/or intraretinal) differed significantly (p = 0.020), with definite fluid on SD-OCT in 45% of the patients for bevacizumab versus 31% for ranibizumab. The occurrence of serious adverse events and adverse events was similar, with 34 SAEs and 256 AEs in the bevacizumab group and 37 SAEs and 299 AEs in the ranibizumab group (p = 0.87 and p = 0.48, respectively). CONCLUSIONS: Bevacizumab was not inferior to ranibizumab. The response to bevacizumab was more varied with higher percentages of both gainers and losers and more frequently observed retinal fluid on SD-OCT at 12 months when compared to the ranibizumab group. TRIAL REGISTRATION: Trialregister.nl NTR1704.

Detecting signs of retinal leakage in exudative AMD using Cirrus OCT versus SL SCAN-1, a novel integrated FD-OCT into a common slit lamp.

PURPOSE: The purpose is to evaluate the interdevice and interobserver agreements between the SL SCAN-1 (a FD-OCT integrated into a common slit lamp) and a standard stand-alone FD-OCT device (the Cirrus) with regard to the presence or absence of signs of leakage in the retina in patients with exudative AMD and treated with anti-VEGF. METHODS: Fifty-six patients, known to have exudative AMD and under treatment with anti-VEGF agents, were included. During a regular follow-up, OCT scans were made with the Cirrus (macular-cube pattern) and the SL SCAN-1 (radial-scan pattern). All scans were graded by two medical retina specialists for signs of intraretinal cysts, subretinal fluid accumulation, and thickening of the neurosensory retina. Presence of signs of leakage was concluded if one or more of the three signs were present. RESULTS: In 91 % of the patients, the observers made identical conclusions for both devices of the presence of signs of leakage, resulting in an interdevice Kappa coefficient of 0.87. For the scans with disagreement about the presence or absence of signs of leakage, positive and negative conclusions were equally distributed between both devices, and differences were restricted to more subtle signs of leakage. CONCLUSION: The interdevice Kappa coefficient of 0.87 shows a high agreement between the SL SCAN-1 and the Cirrus in grading signs of leakage in exudative AMD. OCT images play a pivotal role in the diagnosis and management of exudative diseases like AMD, and the SL SCAN-1 provides a very efficient approach to these patients with the integration of the FD-OCT device into a common slit lamp.

Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: a randomized clinical trial (the BRDME study).

BACKGROUND: The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost-effectiveness study has been designed to substantiate this hypothesis. AIM: To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness. DESIGN: This is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands. OUTCOMES: The primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments.

Scanning beyond the limits of standard OCT with a Fourier domain optical coherence tomography integrated into a slit lamp: the SL SCAN-1.

PURPOSE: With a new Fourier domain optical coherence tomography (FD OCT) device, SL SCAN-1 (Topcon Europe Medical BV, Capelle a/d IJssel, The Netherlands), integrated into a slit-lamp OCT, scans can be obtained through a handheld lens. The necessary adjustment of the reference arm is possible by fast Z-alignment. This study was performed to prove the capability of SL SCAN-1 to scan through a three-mirror contact lens, scanning the peripheral retina and anterior chamber angle. METHODS: Different representative pathologies of the peripheral retina and anterior chamber were simultaneously observed and scanned with the SL SCAN-1. The scans of peripheral retinal lesions were obtained both through a handheld lens and through a three-mirror contact lens. The anterior chamber angle was scanned directly with the SL SCAN-1 in anterior mode, and through the gonio-mirror of a three-mirror contact lens with the SL SCAN-1 in posterior mode. RESULTS: OCT scans could be obtained with the SL SCAN-1 of the peripheral retina through both, a common handheld lens and a three-mirror contact lens. The scans obtained through a three-mirror contact lens were of better quality, visualizing details of the different layers of the retina more clearly. The scans of the anterior chamber, obtained through the gonio-mirror of a three-mirror contact lens, visualized the open anterior chamber angle, with details of fine structures. CONCLUSIONS: The SL SCAN-1 is a unique FD OCT system, which is able to scan not only the posterior pole and anterior segment but also the anterior chamber angle and the more peripheral retina. These four modalities combined into one device could make the SL SCAN-1 a very powerful aid in daily practice.

Fourier Domain Optical Coherence Tomography integrated into a slit lamp; a novel technique combining anterior and posterior segment OCT.

PURPOSE: Fourier Domain Optical Coherence Tomography (FD-OCT) provides high resolution cross-sectional images of the retina and the anterior segment. It has become an important tool in ophthalmology in the examination, diagnosis, and treatment of important and common diseases. Present OCT imaging systems are stand-alone devices. The aim of this paper is to show the quality of images made with a prototype of a Fourier Domain (FD-) OCT imaging system (SLSCAN-1) integrated into a slit lamp. METHODS: Different representative pathologies of the posterior and anterior segment were observed with the slit lamp and simultaneously scanned with a prototype of the slit lamp-integrated FD-OCT system. The clinical interpretation of posterior segment images made with the prototype were compared to those obtained with a stand-alone FD-system (3D-OCT-1000 Mark II, Topcon). RESULTS: Images made with the slit lamp-integrated FD-OCT were of sufficient quality to allow for a correct interpretation of the observed pathological conditions. Conclusions based on the images of the posterior segment of the prototype were identical to the conclusions based on the images of a stand-alone FD-system (3D-OCT-1000 Mark II, Topcon). In addition to the images of the posterior segment, images could be made of the anterior segment. The OCT system did not interfere with the normal functionality of the slit lamp. CONCLUSION: The slit lamp-integrated FD-OCT system provided high quality images of both the anterior and the posterior segment. Scans made with the slit lamp-integrated FD-OCT system could be of use in clinical practice.

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.

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.

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%.

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.

Optical coherence tomography of the Ex-PRESS miniature glaucoma implant.

PURPOSE: To describe the localisation of the Ex-PRESS miniature glaucoma implant with an experimental setup for optical coherence tomography (OCT) of the anterior segment of the eye. METHODS: An OCT scanner, central wavelength 1,280 nm, bandwidth 60 nm, resolution of 12 microm, was built onto a slitlamp to scan the anterior segment of the eye. Five ex-vivo porcine eyes received an Ex-PRESS miniature glaucoma implant and were used as a model to visualise the position of the implant in the anterior segment. RESULTS: In the ex-vivo porcine eyes, the OCT images showed the anatomy of the anterior segment in great detail. The anterior segment OCT was able to visualise the whole outline and position of the implant. The abrupt change in reflectivity going from tissue to the implant resulted in a clear border along the circumference of the whole device. CONCLUSION: In this paper, we have shown that we were able to outline the Ex-PRESS miniature glaucoma implant in the anterior segment of the ex-vivo porcine eye by using an experimental OCT setup built onto a slitlamp. The acquisition time of 0.8 s is short enough to allow for the scanning of patients, and anterior segment OCT is expected to aid in providing answers to the question regarding which parameters will determine the success or failure of such a device.

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.

[Two children with extrapulmonary symptoms due to tuberculosis]. / Twee kinderen met extrapulmonale klachten door tuberculose.

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.

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.

Influence of highly active antiretroviral therapy on the development of CMV disease in HIV positive patients at high risk for CMV disease.

BACKGROUND/AIMS: In the pre-HAART era, HIV positive patients with CD4+ cell counts below 50 cells x10(6)/l, and those with detectable cytomegalovirus (CMV) DNA in their peripheral blood, were considered to be at high risk for the development of CMV disease. With the start of highly active antiretroviral therapy (HAART), a restoration of immune function occurred in these patients, and as a consequence patients became less vulnerable to CMV disease. Since it is not exactly known how HAART influences CMV viral load in peripheral blood and the incidence of CMV disease in high risk HIV positive patients a group of patients was followed before and after initiation of HAART. METHODS: 29 HIV positive patients, seen in the first 3 months of 1996 at the AIDS clinic of the Academic Medical Centre, at high risk for development of CMV disease (positive CMV DNA assay in blood and/or CD4+ cell count below 50 cells x10(6)/l), not receiving anti-CMV maintenance therapy, were included in a prospective cohort study. HAART was started in the second trimester of 1996. Patients were evaluated for the occurrence of CMV retinitis, or CMV disease elsewhere, comparing the incidence of CMV events before and after the start of HAART. Following the introduction of HAART, CD4+ cell counts and quantitative polymerase chain reaction (PCR) for CMV DNA in blood were monitored in all patients who remained alive and were not receiving anti-CMV maintenance therapy (n=22). Follow up was performed until August 1998; the mean follow up after the start of HAART was 14.9 months (range 8-22 months). RESULTS: In the pre-HAART period four patients developed CMV disease, and four died (without clinically manifest CMV disease). After the start of HAART no patient developed CMV disease or died. With HAART, the mean CD4+ cell counts increased from 34 cells x10(6)/l to 194 cells x10(6)/l at the end of follow up. CMV DNA could be detected in the blood of 11 patients. Quantification showed a decline in the amount of detectable DNA during follow up. At the last examination only one patient showed a positive PCR assay. This was the only patient with a CD4+ cell count remaining below 100 cells x10(6)/l. CONCLUSION: In HIV positive patients at high risk of CMV retinitis, either with a positive CMV PCR assay in blood and/or with CD4+ cell counts below 50 cell x10(6)/l, HAART causes a dramatic decrease in the occurrence of CMV disease. This decrease is paralleled by an increase in CD4+ cell count, and a decrease in the amount of CMV DNA in the blood, which was below detection levels in all patients with CD4+ cell counts above 100 cells x10(6)/l.