Thomas Theelen

Acute endophthalmitis after cataract surgery: 250 consecutive cases treated at a tertiary referral center in the Netherlands.

PURPOSE To evaluate the clinical characteristics, bacterial culture, and visual outcome of patients with acute endophthalmitis after cataract surgery. DESIGN Retrospective consecutive interventional case series. METHODS Clinical notes from patients treated for acute endophthalmitis after cataract surgery in a single center from 1996 to 2006 were reviewed. Patients with less than 1 month of follow-up and missing bacterial cultures were excluded. Vitreous biopsy or primary vitrectomy followed by intravitreal injection of vancomycin and ceftazidime (+/- prednisolone) was performed. Main outcome measures were bacterial culture and final visual acuity. RESULTS Bacterial cultures (total 250 cases) showed bacterial growth in 166 cases (66.4%). From these 166 cultures, 89 (53.6%) revealed gram-positive coagulase-negative, 63 (38.0%) other gram-positive, 10 (6.0%) gram-negative, and 4 (2.4%) polymicrobial cultures. Vitreous biopsy with intravitreal antibiotics injection was performed in 225 (90.0%) of cases. Primary vitrectomy with intravitreal antibiotics was performed in 25 eyes (10.0%). Final visual acuity >/=0.5 was achieved in 129 (51.6%) of all cases, 54 (60.7%) of the 89 gram-positive coagulase-negative cultures, 20 (31.7%) of the 63 other gram-positive cultures, 5 (50.0%) of the 10 gram-negative cultures, and 9 (45.0%) of the 20 Staphylococcus aureus cultures. There was no additional effect for treatment by primary vitrectomy or intravitreal prednisolone. CONCLUSIONS Treatment outcome after endophthalmitis is highly dependent on the causative organism. Treatment outcomes for gram-negative bacteria and S. aureus may be better than previously reported. Prompt treatment of endophthalmitis remains essential and the role of complete primary vitrectomy remains subject to debate.

Intraocular inflammation following endotamponade with high-density silicone oil.

BackgroundThe use of a mixture of silicone oil and partially fluorinated alkanes (high-density silicone oil) has recently been suggested as intraocular tamponade in complicated retinal detachment of the inferior quadrants. We describe a series of patients who developed a clinical picture resembling anterior granulomatous uveitis following endotamponade with high-density silicone oil.MethodsWe evaluated 19 eyes of 18 patients who underwent pars plana vitrectomy and intraocular tamponade with high-density silicone oil (Oxane HD®). The indication for this type of intraocular tamponade was limited to cases with complicated retinal detachment of the inferior quadrants. Oxane HD® was removed after a mean period of 3 months.ResultsOne to eight weeks following vitrectomy with high-density silicone oil, an intraocular inflammation was observed in 7 of 19 eyes (37%). These eyes presented with keratic precipitates (KP), pigmented clumps in the inferior part of the anterior chamber and increased anterior chamber cellular reaction. This inflammatory response did not react to topical steroids. In addition to KP a considerable amount of cellular precipitation was noted on the surface of the oil bubble. Strikingly, the intraocular inflammatory signs completely resolved following removal of the high-density silicone oil.ConclusionsAn inflammatory response, resembling granulomatous uveitis, occurs in a significant number of patients after high-density silicone oil endotamponade. It is likely that this vitreous substitute is an immunogenic agent, given the complete resolution of the inflammation after removal of the high-density silicone oil. The routine use of this newly developed silicone oil should therefore await the outcome of additional controlled clinical trials.

Fast Convolutional Neural Network Training Using Selective Data Sampling: Application to Hemorrhage Detection in Color Fundus Images

Convolutional neural networks (CNNs) are deep learning network architectures that have pushed forward the state-of-the-art in a range of computer vision applications and are increasingly popular in medical image analysis. However, training of CNNs is time-consuming and challenging. In medical image analysis tasks, the majority of training examples are easy to classify and therefore contribute little to the CNN learning process. In this paper, we propose a method to improve and speed-up the CNN training for medical image analysis tasks by dynamically selecting misclassified negative samples during training. Training samples are heuristically sampled based on classification by the current status of the CNN. Weights are assigned to the training samples and informative samples are more likely to be included in the next CNN training iteration. We evaluated and compared our proposed method by training a CNN with (SeS) and without (NSeS) the selective sampling method. We focus on the detection of hemorrhages in color fundus images. A decreased training time from 170 epochs to 60 epochs with an increased performance-on par with two human experts-was achieved with areas under the receiver operating characteristics curve of 0.894 and 0.972 on two data sets. The SeS CNN statistically outperformed the NSeS CNN on an independent test set.

Fundus autofluorescence imaging of retinal dystrophies

Fundus autofluorescence (FAF) is a non-invasive imaging technique that enables the visualization of lipofuscin changes in the retinal pigment epithelium. This study aims to illustrate the spectrum of FAF changes in a variety of retinal dystrophies. For this purpose, we examined patients with retinal dystrophies such as Stargardt disease, Best vitelliform macular dystrophy, and retinal dystrophies associated with mutations in the peripherin/RDS gene. All retinal dystrophies were confirmed by molecular genetic analysis. A broad range of characteristic FAF patterns was observed. Our results indicate that FAF imaging constitutes a useful additive tool in the diagnosis and follow-up of various retinal dystrophies.

Mutations in the peripherin/RDS gene are an important cause of multifocal pattern dystrophy simulating STGD1/fundus flavimaculatus.

Aim: To describe the phenotype and to analyse the peripherin/RDS gene in 10 unrelated families with multifocal pattern dystrophy simulating Stargardt disease (STGD1). Methods: The probands of 10 families and 20 affected family members underwent an ophthalmic examination including dilated fundus examination, fundus autofluorescence imaging and optical coherence tomography (OCT). In all probands and in selected family members, fluorescein angiography, electrophysiological testing and visual field analysis were performed. Blood samples were obtained from affected and unaffected family members for analysis of the peripherin/RDS gene. Results: All 10 probands carried mutations in the peripherin/RDS gene. Nine different mutations were identified, including six mutations that were not described previously. All probands showed a pattern dystrophy with yellow–white flecks in the posterior pole that strongly resembled the flecks seen in STGD1, on ophthalmoscopy as well as on autofluorescence and OCT. Clinical findings in the family members carrying the same mutation as the proband were highly variable, ranging from no visible abnormalities to retinitis pigmentosa. Conclusions: Mutations in the peripherin/RDS gene are the major cause of multifocal pattern dystrophy simulating STGD1/fundus flavimaculatus. This autosomal dominant disorder should be distinguished from autosomal recessive STGD1, in view of the different inheritance pattern and the overall better visual prognosis.

Central Areolar Choroidal Dystrophy

OBJECTIVE To describe the clinical characteristics, follow-up data and molecular genetic background in a large group of patients with central areolar choroidal dystrophy (CACD). DESIGN Retrospective case series study. PARTICIPANTS One hundred three patients with CACD from the Netherlands. METHODS Ophthalmologic examination, including color vision testing, fundus photography, fluorescein angiography, fundus autofluorescence (FAF) imaging, optical coherence tomography, full-field electroretinography (ERG), multifocal ERG, and electrooculography. Blood samples were obtained for DNA extraction and subsequent analysis of the peripherin/RDS gene, as well as haplotype analysis. MAIN OUTCOME MEASURES Clinical characteristics, phenotypic range, clinical follow-up data, and FAF findings. RESULTS The mean age at onset of visual loss was 46 years, with subsequent gradual deterioration in visual acuity. Ninety-eight patients carried a p.Arg142Trp mutation in peripherin/RDS, whereas 5 affected members of a CACD family carried a p.Arg172Gln peripherin/RDS mutation. A remarkable variation in disease severity was observed, and nonpenetrance was seen up to the age of 64 years, in up to 21% of mutation carriers. However, most macular lesions in mutation carriers displayed a typical stage of CACD. Substantial changes were seen on FAF imaging after a mean follow-up period of 11 months. Electrophysiologic data were consistent with a central cone dystrophy. The age at onset and phenotypic characteristics of CACD show considerable overlap with atrophic age-related macular degeneration (AMD). The great majority of p.Arg142Trp-carrying CACD patients originated from the southeast region of the Netherlands, and haplotype analysis strongly suggested a common founder mutation. CONCLUSIONS When caused by a p.Arg142Trp mutation in the peripherin/RDS gene, CACD causes a central cone dystrophy phenotype. This mutation, which most likely originates from a common founder in most patients, is associated with a significant degree of nonpenetrance. In the elderly patient, CACD may be confused with AMD, especially in cases with decreased penetrance.

A novel technique for self-sealing, wedge-shaped pars plana sclerotomies and its features in ultrasound biomicroscopy and clinical outcome

PURPOSE To investigate a new type of self-sealing pars plana sclerotomy clinically and by means of ultrasound biomicroscopy and to compare the outcome with conventionally sutured sclerotomies. DESIGN Prospective, nonrandomized clinical trial. METHODS Twenty-one patients underwent pars plana vitrectomy either with (control group) or without suturing (study group) at the Institute of Ophthalmology, University Medical Centre Nijmegen, The Netherlands, between January 1 and March 31, 2002. One day and 6 to 8 weeks postoperatively, the sclerotomy sites were studied by clinical examination and ultrasound biomicroscopy. Results were graded according to verbal descriptor scales. RESULTS The study included 21 patients scheduled for pars plana vitrectomy of one eye. Mean follow-up time was 6.5 weeks (range, 6-8). Three patients were lost to follow-up. Of the remaining patients, 12 had self-sealing wedge-sclerotomies and six were conventionally operated. No intraoperative complications occurred in any participant and no visual loss or postoperative hypotony was observed. On the first day after surgery there was significantly more scleral dehiscence in the control group (P =.012). This divergence disappeared during the follow-up period. All other differences noticed were not statistically significant. CONCLUSIONS Our novel technique of sutureless wedge-shaped sclerotomy allows the creation of simple, reliable, and self-sealing pars plana openings. Clinical examination and assessment by ultrasound biomicroscopy showed results to be at least as safe as conventionally sutured sclerotomies. This new method allows stable intraoperative ocular pressure conditions and seems promising.

OCT Angiography Compared to Fluorescein and Indocyanine Green Angiography in Chronic Central Serous Chorioretinopathy.

PURPOSE Abnormal choroidal blood flow is considered important in the pathogenesis of chronic central serous chorioretinopathy (CSC). Optical coherence tomography (OCT) angiography can image ocular blood cell flow and could thus provide novel insights in disease mechanisms of CSC. We evaluated depth-resolved flow in chronic CSC by OCT angiography compared to fluorescein angiography (FA) and indocyanine green angiography (ICGA). METHODS Eighteen eyes with chronic CSC, and six healthy controls, were included. Two human observers annotated areas of staining, hypofluorescence, and hotspots on FA and ICGA, and areas of abnormal flow on OCT angiography. Interobserver agreement in annotating OCT angiography and FA/ICGA was measured by Jaccard indices (JIs). We assessed colocation of flow abnormalities and subretinal fluid visible on OCT, and the distance between hotspots on ICGA from flow abnormalities. RESULTS Abnormal areas were most frequently annotated in late-phase ICGA and choriocapillary OCT angiography, with moderately high (median JI, 0.74) and moderate (median JI, 0.52) interobserver agreement, respectively. Abnormalities on late-phase ICGA and FA colocated with those on OCT angiography. Aberrant choriocapillary OCT angiography presented as foci of reduced flow surrounded by hyperperfused areas. Hotspots on ICGA were located near hypoperfused spots on OCT angiography (mean distance, 168 μm). Areas with current or former subretinal fluid were colocated with flow abnormalities. CONCLUSIONS On OCT angiography, chronic CSC showed irregular choriocapillary flow patterns, corresponding to ICGA abnormalities. These results suggest focal choriocapillary ischemia with surrounding hyperperfusion that may lead to subretinal fluid leakage.

Clinical and molecular genetic analysis of best vitelliform macular dystrophy.

Purpose: To describe the phenotype of Best vitelliform macular dystrophy (BVMD) and to evaluate genotype–phenotype and histopathologic correlations. Methods: Retrospective analysis of patients with BVMD who underwent an extensive ophthalmic examination, including best-corrected Snellen visual acuity, fundus examination by indirect ophthalmoscopy, fundus photography, fundus autofluorescence, optical coherence tomography, fundus fluorescein angiography, and electrooculography. In addition, molecular genetic analysis of the BEST1 gene was performed in all patients. Results: We examined 40 eyes of 20 patients with BVMD. Sixteen eyes (40%) had a well-defined BVMD stage, whereas 18 eyes displayed characteristics attributable to different stages. Six eyes had an atypical form of BVMD. Fundus autofluorescence and optical coherence tomography frequently detected abnormalities that were not visible on ophthalmoscopy. All patients carried a mutation in the BEST1 gene. Molecular genetic analysis identified 8 different BEST1 mutations in 15 families, including 2 novel mutations (p.Gly299Ala and p.Ile3Thr). Genotype–phenotype correlation was limited, as we observed a broad phenotypic range in association with a single BEST1 mutation. However, the p.Ala243Val seems to cause a mild and relatively invariable BVMD phenotype. Conclusion: A broad phenotypic variability may be observed in BVMD, even with a single BEST1 mutation. Fundus autofluorescence and optical coherence tomography are valuable noninvasive imaging techniques for phenotyping and follow-up of BVMD patients.

Mutations in the EYS gene account for approximately 5% of autosomal recessive retinitis pigmentosa and cause a fairly homogeneous phenotype.

OBJECTIVE To determine the prevalence of mutations in the EYS gene in a cohort of patients affected by autosomal recessive retinitis pigmentosa (RP) and to describe the associated phenotype. DESIGN Case series. PARTICIPANTS Two hundred forty-five patients affected by autosomal recessive RP. METHODS All coding exons of EYS were screened for mutations by polymerase chain reaction amplification and sequence analysis. All 12 patients carrying mutations in EYS were re-examined, which included Goldmann kinetic perimetry, electroretinography, and high-resolution spectral-domain optical coherence tomography (OCT). MAIN OUTCOME MEASURES DNA sequence variants, best-corrected visual acuity, fundus appearance, visual field assessments using Goldmann kinetic perimetry, electroretinogram responses, and OCT images. RESULTS Nine novel truncating mutations and one previously described mutation in EYS were identified in 11 families. In addition, 18 missense changes of uncertain pathogenicity were found. Patients carrying mutations in EYS demonstrated classic RP with night blindness as the initial symptom, followed by gradual constriction of the visual field and a decline of visual acuity later in life. The onset of symptoms typically occurred between the second and fourth decade of life. The fundus displayed bone spicules increasing in density with age and generalized atrophy of the retinal pigment epithelium and choriocapillaris with relative sparing of the posterior pole until later in the disease process, when atrophic macular changes occurred. CONCLUSIONS Mutations in EYS account for approximately 5% of autosomal recessive RP patients in a cohort of patients consisting predominantly of patients of western European ancestry. The EYS-associated RP phenotype is typical and fairly homogeneous in most patients.