Contact lenses in paediatric aphakia in the Netherlands; A multicentre retrospective chart study.

PURPOSE: The main aim of this study was to evaluate the type, parameters, loss and complications of contact lenses (CLs) in the treatment of paediatric aphakia over a 10-year period. METHODS: This retrospective multicentre chart review included the files of aphakic CL wearers under the age of 9 years old that were treated between 2008 and 2018. Patients with traumatic aphakia and scarring of the cornea were excluded. The following data were collected; demographic data, cataract type (congenital or secondary), CL type, parameters and wearing time, reason for replacement and discontinuation of the CLs, visual acuity (VA), prophylactic use of antibiotics (ABs), and complications. RESULTS: Ninety-one aphakic children (132 eyes) were fitted with soft CLs. The median age of cataract extraction was 10.50 weeks (interquartile range (IQR) 7,15) in the congenital cataract group and 112 weeks (IQR 41,285) in the secondary cataract group. At the initial fitting a silicone elastomer CL was fitted in 86 % and a silicone hydrogel CL in 12 %, the remaining 2 % were mixed CL types. The median CL power at baseline was + 29 D (IQR 25,32) and after 3 years of wear the median power had shifted significantly to + 20 D (IQR 17,26), P < 0.001. A total of 1083 extra CL replacements were needed of which 414 in the first year of wear. Of these 414 replacements almost half (46 %;n = 191) were due to loss of the CL. Complications developed in 8 (9 %) cases and 7 (8 %) patients discontinued CL wear. CONCLUSION: This paper confirms that paediatric aphakia can be successfully treated with soft CLs with low rates of complications and discontinuation encountered. Unscheduled CL replacements due to loss are a concern, especially in the first year, and are straining for both the care giver and medical system. Attentive care and clear information is advised during the first year of CL wear.

Retina-arrestin specific CD8+ T cells are not implicated in HLA-A29-positive birdshot chorioretinitis.

BACKGROUND: HLA-A29-positive birdshot chorioretinitis (BCR) is an inflammatory eye disorder that is generally assumed to be caused by an autoimmune response to HLA-A29-presented peptides from retinal arrestin (SAG), yet the epitopes recognized by CD8+ T cells from patients remain to be identified. OBJECTIVES: The identification of natural ligands of SAG presented by HLA-A29. To quantify CD8+ T cells reactive to antigenic SAG peptides presented by HLA-A29 in patients and controls. METHODS: We performed mass-spectrometry based immunopeptidomics of HLA-A29 of antigen-presenting cell lines from patients engineered to express SAG. MHC-I Dextramer technology was utilised to determine expansion of antigen-specific CD8+ T cells reactive to SAG peptides in complex with HLA-A29 in a cohort of BCR patients, HLA-A29-positive controls, and HLA-A29-negative controls. RESULTS: We report on the naturally presented antigenic SAG peptides identified by sequencing the HLA-A29 immunopeptidome of antigen-presenting cells of patients. We show that the N-terminally extended SAG peptide precursors can be trimmed in vitro by the antigen-processing aminopeptidases ERAP1 and ERAP2. Unexpectedly, no enhanced antigen engagement by CD8+ T cells upon stimulation with SAG peptides was observed in patients or HLA-A29-positive controls. Multiplexed HLA-A29-peptide dextramer profiling of a case-control cohort revealed that CD8+ T cells specific for these SAG peptides were neither detectable in peripheral blood nor in eye biopsies of patients. CONCLUSIONS: Collectively, these findings demonstrate that SAG is not a CD8+ T cell autoantigen and sharply contrast the paradigm in the pathogenesis of BCR. Therefore, the mechanism by which HLA-A29 is associated with BCR does not involve SAG.

The treatment of ocular hypotony after trabeculectomy with a scleral lens: A case series.

PURPOSE: Ocular hypotony after trabeculectomy may be treated medically, surgically and with a tamponade. Three cases are reported in which a scleral lens was applied to treat ocular hypotony after mitomycin C (MMC) augmented trabeculectomy. METHODS: In this retrospective case series the records of three eyes of three patients who developed ocular hypotony after they had undergone trabeculectomy augmented with MMC were evaluated. The patients were between 11 and 69 years of age and the intraocular pressure (IOP) after surgery ranged between 3 and 6 mmHg. All three patients showed a negative Seidel test; one had suspected hypotonic maculopathy and one had a collapsed anterior chamber. After unsuccessful treatment with large bandage lenses all three patients were subsequently fitted with a scleral lens. The scleral lens was fitted to fully cover and compress the bleb. Scleral lenses were worn continuously with a check-up after one night of wear and subsequent check-ups when needed. One patient continued to wear the scleral lens for a further 6.5 months on a daily wear basis. RESULTS: In all three eyes the IOP was higher after wearing the scleral lens. Two patients stopped wearing the scleral lens after the IOP was stable. One patient developed a cataract; the cataract surgery was combined with a bleb revision and scleral lens wear was therefore discontinued. DISCUSSION: The scleral lens might be a useful tool in the treatment of ocular hypotony after trabeculectomy augmented MMC surgery. The effect of the scleral lens on the ocular pressure is unpredictable. Caution is advised in vulnerable corneas due to risk factors such as hypoxia and infection. Further research is warranted to establish the safety of the procedure, the patient selection and the overall success in a larger patient group.

An Ocular Protein Triad Can Classify Four Complex Retinal Diseases.

Retinal diseases generally are vision-threatening conditions that warrant appropriate clinical decision-making which currently solely dependents upon extensive clinical screening by specialized ophthalmologists. In the era where molecular assessment has improved dramatically, we aimed at the identification of biomarkers in 175 ocular fluids to classify four archetypical ocular conditions affecting the retina (age-related macular degeneration, idiopathic non-infectious uveitis, primary vitreoretinal lymphoma, and rhegmatogenous retinal detachment) with one single test. Unsupervised clustering of ocular proteins revealed a classification strikingly similar to the clinical phenotypes of each disease group studied. We developed and independently validated a parsimonious model based merely on three proteins; interleukin (IL)-10, IL-21, and angiotensin converting enzyme (ACE) that could correctly classify patients with an overall accuracy, sensitivity and specificity of respectively, 86.7%, 79.4% and 92.5%. Here, we provide proof-of-concept for molecular profiling as a diagnostic aid for ophthalmologists in the care for patients with retinal conditions.

Young age as a risk factor for complicated course and visual outcome in intermediate uveitis in children.

OBJECTIVE: To identify prognostic factors in intermediate uveitis (IU) in children. METHODS: Retrospective case series of 35 patients with onset of IU ≤16 years and a minimum follow-up of 1 year. Demographic and numerous clinical data were documented. Visual outcomes and development of complications were analysed in relation to age of onset and ocular signs at presentation. RESULTS: Forty-six per cent of patients had onset ≤7 years, and 54% >7 years. The younger-onset group had a shorter event-free survival for secondary glaucoma (p=0.04) and vitreous haemorrhage (p=0.01). The mean age of onset in children with cataract (5.9 vs 8.7 years), glaucoma (5.0 vs 8.4) and vitreous haemorrhage (5.6 vs 8.5) was lower than in children without these complications (all p=0.03). Frequencies of other complications did not differ between both groups. The younger-onset group had worse BCVAs at presentation (0.3 vs 0.6), at 1 year (0.4 vs 0.9) and at 3 years' follow-up (0.6 vs 0.9; all p≤0.04), and they needed longer treatment (p=0.01). Children with young onset of IU reached remission less frequently (p=0.05). Development of cystoid macular oedema was independently associated with papillitis (adjusted HR=3.4; p=0.02) and snowbanking (adjusted HR=3.3; p=0.03) at presentation. Other complications at onset were not predictive for future complications. CONCLUSIONS: Children with young onset of IU carry a higher risk of complications and worse visual outcome. The authors would recommend considering more intensive monitoring and earlier threshold for systemic treatment in those children with risk factors as early onset, papillitis and/or snowbanking at initial presentation.

Herpetic encephalitis is a risk factor for acute retinal necrosis.

BACKGROUND: Acute retinal necrosis (ARN) has been observed in several cases after herpetic encephalitis (HE). ARN is a devastating ocular disease with a very disappointing visual outcome. Therefore, early recognition and diagnosis are crucial. OBJECTIVE: To study the association between ARN and preceding neurologic illness, especially the co-occurrence of HE in patients with ARN; to compare the causal agent in ARN and HE; and to determine the visual outcome of ARN with HE vs ARN without HE. METHODS: A retrospective study including ophthalmologic and neurologic follow-up together with virologic data of patients with ARN. PARTICIPANTS: Seven patients with ARN diagnosed with a history of HE (13.5%) out of a source population of 52 patients with ARN admitted to a major academic ophthalmologic referral center between 1983 and 2008. RESULTS: In five out of seven patients unilateral ARN occurred after HE under immunocompetent conditions, and both ARN and HE were caused by the herpes simplex virus (HSV), whereas the other two patients were immunocompromised, had bilateral ARN, and both ARN and HE were caused by the varicella zoster virus (VZV). The latency period between the HE and the ARN was shorter when VZV was involved than with HSV (5 weeks vs 20.6 months). The visual outcome in patients with ARN with HE, as defined by legally blind eyes after a follow-up of 1 year, did not differ significantly from patients with ARN without HE. CONCLUSION: Herpetic encephalitis seems to be a risk factor for acute retinal necrosis syndrome. Since treatment may improve the outcome at least for the second eye, it is relevant for clinicians to be aware of this association.

[Two children with arthritis and uveitis: the clinical importance of ophthalmologic screening in children with juvenile arthritis]. / Twee kinderen met reuma en uveïtis: het klinisch belang van oogheelkundige screening bij kinderen met jeugdreuma.

Two girls, aged 8 and 13 years, with a history of arthritis presented with already advanced uveitis. Neither girl had been screened for uveitis by an ophthalmologist according to the recommendations of the American Academy of Pediatrics. Both patients had extensive posterior synechiae (adhesions between lens and iris) at their first ophthalmologic examination, which is associated with an unfavourable prognosis. At the last follow-up, the first patient had undergone seven ocular operations: five for glaucoma and two cataract surgeries. Uveitis occurs in 20% of children with juvenile idiopathic arthritis. The visual outcome of uveitis is negatively influenced by the presence of ocular complications at the first ophthalmologic examination. Ophthalmologic screening of children with juvenile idiopathic arthritis is very important because it is a common cause ofuveitis in childhood, the uveitis is usually asymptomatic, and there are sight-threatening complications. Screening is always important, even when the arthritis is in remission.

Fabrication and characterization of high-temperature microreactors with thin film heater and sensor patterns in silicon nitride tubes.

In this paper the fabrication and electrical characterization of a silicon microreactor for high-temperature catalytic gas phase reactions, like Rh-catalyzed catalytic partial oxidation of methane into synthesis gas, is presented. The microreactor, realized with micromachining technologies, contains silicon nitride tubes that are suspended in a flow channel. These tubes contain metal thin films that heat the gas mixture in the channel and sense its temperature. The metal patterns are defined by using the channel geometry as a shadow mask. Furthermore, a new method to obtain Pt thin films with good adhesive properties, also at elevated temperatures, without adhesion metal is implemented in the fabrication process. Based on different experiments, it is concluded that the electrical behaviour at high temperatures of Pt thin films without adhesion layer is better than that of Pt/Ta films. Furthermore, it is found that the temperature coefficient of resistance (TCR) and the resistivity of the thin films are stable for up to tens of hours when the temperature-range during operation of the microreactor is below the so-called "burn-in" temperature. Experiments showed that the presented suspended-tube microreactors with heaters and temperature sensors of Pt thin films can be operated safely and in a stable way at temperatures up to 700 degrees C for over 20 h. This type of microreactor solves the electrical breakdown problem that was previously reported by us in flat-membrane microreactors that were operated at temperatures above 600 degrees C.

Heparin-coated bypass circuits: effects on inflammatory response in pediatric cardiac operations.

BACKGROUND: This study was designed to investigate whether clinical signs of the inflammatory response in pediatric cardiac patients are reduced by heparin-coated cardiopulmonary bypass circuits and how this could be explained by differences in the pathophysiologic mechanisms involved. METHODS: In a randomized, prospective study 19 patients underwent cardiopulmonary bypass either with Carmeda BioActive Surface bypass circuits (n = 9) or with identical noncoated circuits (control, n = 10). Clinical parameters were recorded during the first 48 hours after the start of operation. Blood samples for determination of terminal complement complex, soluble form of E-selectin, and beta-thromboglobulin were obtained perioperatively up to 24 hours after operation. RESULTS: All clinical and inflammatory mediators showed a tendency in favor of the group with heparin-coated circuits. When analyzed on a point-by-point basis there were significant differences in postoperative central body temperature, soluble E-selectin levels, and beta-thromboglobulin levels (all p < 0.05). CONCLUSIONS: These data suggest that the use of heparin-coated cardiopulmonary bypass offers clinical benefit and tends to reduce the release of inflammatory mediators.

Serologic and polymerase chain reaction analysis of intraocular fluids in the diagnosis of infectious uveitis.

PURPOSE: Infectious uveitis entities are usually rapidly progressive blinding diseases that can be prevented by prompt administration of specific antimicrobial therapy. With the aim of improving early diagnosis in patients with infectious uveitis, intraocular fluid samples from patients with sight-threatening posterior uveitis were investigated to determine the causative agent. METHODS: Thirty-eight patients with acquired immunodeficiency syndrome (AIDS) and retinitis, eight immunosuppressed patients with retinitis, 16 immunocompetent patients with acute retinal necrosis, and 22 immunocompetent patients with toxoplasmic retinochoroiditis were analyzed by polymerase chain reaction for the presence of herpesviruses and Toxoplasma gondii DNA and for local antibody production against these microorganisms. RESULTS: In patients with AIDS and retinitis, polymerase chain reaction was positive for cytomegalovirus DNA in 21 (91%) of the 23 ocular fluid samples obtained during active cytomegalovirus retinitis, whereas local antibody production analysis was negative in all cases. In acute retinal necrosis, varicella-zoster virus or herpes simplex virus could be established as the inciting agent in 81% of the cases, using the combination of both techniques. Polymerase chain reaction was positive in all samples obtained within two weeks after the onset of disease. Toxoplasma gondii DNA was detected in 4 of 13 samples (31%) from immuno-competent patients with active toxoplasmic retinochoroiditis; in each case, local antibody production was also detected. In contrast, no local antibody production was observed in two of three samples from transplant recipients that were positive for T. gondii DNA. All the control samples tested were negative for the above-mentioned tests. CONCLUSIONS: In patients with AIDS, polymerase chain reaction analysis is preferable above local antibody production in detecting the inciting agent of retinitis. In other cases, the combination of both techniques can make a valuable contribution to the diagnosis.

Low mature TGF-beta 2 levels in aqueous humor during uveitis.

PURPOSE: To investigate whether transforming growth factor-beta 2 (TGF-beta 2), a strong immunosuppressive factor normally present in aqueous humor, is involved in the inflammatory process of clinical uveitis. METHODS: Mature TGF-beta 2 levels were determined in aqueous humor samples of 9 patients with Fuchs' heterochromic cyclitis, aqueous humor samples of 21 patients with other uveitis entities, and vitreous fluid samples of 19 patients with uveitis by using a commercially available sandwich ELISA: Total TGF-beta 2 levels in ocular fluids were measured after heat activation. Aqueous humor samples from patients with cataract and glaucoma and vitreous fluid samples from eye bank eyes were tested as controls. Albumin levels, determined by radial immunodiffusion, were used as a measure of the disruption of the blood aqueous barrier. RESULTS: Significantly lower mature TGF-beta 2 levels were detected in aqueous humor samples of patients with uveitis, compared to the two control groups without intraocular inflammation. Samples of patients with uveitis without detectable mature TGF-beta 2 did contain latent TGF-beta 2 levels (504 to 6024 pg/ml). In aqueous humor, there was a significant negative correlation between mature TGF-beta 2 and albumin levels. No mature TGF-beta could be detected in vitreous fluid. Total TGF-beta 2 levels in vitreous fluid were significantly lower in samples from patients with uveitis than in samples from eye bank eyes. CONCLUSION: These results indicate that the mature TGF-beta 2 levels in aqueous humor and the total TGF-beta 2 levels in vitreous fluid are reduced during ocular inflammation. In aqueous humor, this might be caused by binding of mature TGF-beta to serum proteins, for instance, alpha 2-macroglobulin, or by a disturbance in the activation process of latent TGF-beta 2.

Detection of intraocular antibody production to herpesviruses in acute retinal necrosis syndrome.

In order to improve the determination of the causative agent in acute retinal necrosis syndrome, we evaluated the detection of intraocular antibody production to herpesviruses in 28 patients with this disease. Intraocular antibody production was determined by calculation of the Goldmann-Witmer coefficient whereby specific antibody titers in the inflamed eye and circulation are related to the total IgG content in ocular fluid and serum. Specific antibody titers to herpesviruses and Toxoplasma were determined by the indirect immunofluorescence technique. Thirty-five patients with ocular toxoplasmosis, cataract, or proliferative vitreoretinal disorders were tested as controls. By this technique, intraocular antibody production to varicella zoster virus or herpes simplex virus could be established in 16 (57%) of the patients with the typical clinical features of acute retinal necrosis, compared to none of the controls. Of the 33 affected eyes, 21 (64%) had a visual outcome of less than 20/200. We concluded that detection of intraocular antibody production to herpesviruses may be a useful diagnostic tool in establishing the causative agents in acute retinal necrosis.

Chemoattractant and neutrophil degranulation activities related to interleukin-8 in vitreous fluid in uveitis and vitreoretinal disorders.

PURPOSE: To investigate whether the cytokine interleukin-8 (IL-8), a strong chemoattractant and activator for neutrophils, is responsible for neutrophil infiltration and degranulation in the eye in uveitis. METHODS: IL-8 and elastase were measured with specific enzyme-linked immunoassays in vitreous fluid samples obtained from 69 patients with various uveitis entities. Vitreous fluid of nonuveitis patients and eye bank eyes served as controls. The chemotactic activity of vitreous fluid was tested with the Boyden chamber technique. RESULTS: IL-8 was detected in 45% of the vitreous fluid samples from uveitis patients and in 26% of vitreous fluid samples from nonuveitis patients. Vitreous fluid samples with IL-8 levels exceeding 100 pg/ml were chemotactic for neutrophils. This chemotactic activity could be blocked by 41% to 79% with a monoclonal anti-IL-8 antibody. Elastase levels in vitreous fluid of uveitis patients with detectable IL-8 were significantly higher than those in vitreous fluid samples with no detectable IL-8. CONCLUSION: These results indicate that IL-8 participates in the inflammatory processes in the eye by attracting and degranulating neutrophils. It is suggested that these processes contribute to the pathogenesis of tissue destruction in uveitis.

Analysis of IL-6 levels in human vitreous fluid obtained from uveitis patients, patients with proliferative intraocular disorders and eye bank eyes.

Several studies suggest a role for IL-6 in the pathogenesis of uveitis. Earlier we have shown that aqueous humour obtained from patients with uveitis contained raised levels of IL-6. In the study described here we investigated the IL-6 levels in vitreous fluid samples obtained from 75 uveitis patients with different uveitis entities. Vitreous samples from 14 patients with proliferative intraocular disorders (PID) and 29 eye bank eyes were used as controls. All the samples were tested in the IL-6 B9 bioassay as well as in a sensitive ELISA for IL-6. Raised IL-6 levels were detected in the vitreous fluid of uveitis patients as well as patients with PID, implicating IL-6 as a common inflammatory mediator. The highest mean level of IL-6 was found in the vitreous fluid of patients with acute retinal necrosis. The mean IL-6 levels measured by the ELISA were higher compared to the levels measured by the B9 bioassay. This may be caused by the presence of B9 bioassay inhibitory factors in the vitreous fluid of these patients.

Optimization of the in vitro glucuronidation of ibuprofen using factorial design.

Ibuprofen was chosen as a test compound to perform a multivariate design in order to determine the highest yield of the in vitro glucuronidation reaction in relation to the concentration of reacting and activating substances. Preliminary studies with a univariate design indicated that the concentration of Mg2+ had no significant effect on the glucuronidation and that Triton X-100 could be omitted as it appeared to inhibit the glucuronidation. In a 3(3) factorial design the influence of concentrations of ibuprofen, UDP glucuronic acid and enzyme, respectively, on the yield of ibuprofen glucuronide was established. It was concluded that the highest amount of ibuprofen glucuronide formed (within the limits of this design) was achieved with an ibuprofen concentration of 486 microM, a UDP-glucuronic acid concentration of 3 mM and an enzyme concentration of 3.57 mg/ml. Using this methodology it is possible to optimize the glucuronidation yield in a more rational way, which can be useful in the upscaling of enzymatic reactions.