ENDOGENOUS ENDOPHTHALMITIS ASSOCIATED WITH INJECTION DRUG USE COMPARED WITH OTHER ETIOLOGIES.

PURPOSE: To compare features of endogenous endophthalmitis associated with injection drug use (IDU) to endogenous endophthalmitis from other etiologies. METHODS: The authors retrospectively collected data on patients with endogenous endophthalmitis due to IDU or other causes from three academic tertiary care centers over a six-year period. Differences in presenting characteristics, culture results, treatment, and visual acuity were compared between groups. RESULTS: Thirty-eight patients (34%) had IDU-associated endogenous endophthalmitis while 75 patients (67%) had endogenous endophthalmitis from other causes. Compared with patients in the non-IDU group, IDU patients were significantly younger, more frequently male, had longer duration of symptoms at diagnosis, and were less likely to have bilateral disease ( P < 0.05 for all). Injection drug use patients were less likely to have a systemic infection source identified (29% vs. 71%, P < 0.001) or have positive cultures (47% vs. 80%, P < 0.001). The IDU group was less likely to be admitted to the hospital (71% vs. 92%, P = 0.005) and less likely to receive treatment with intravenous antimicrobials (55% vs. 83%, P = 0.003). Visual acuity did not significantly differ between groups. CONCLUSION: Endophthalmitis related to IDU presents in younger patients with less comorbidities and frequently without positive cultures or an identifiable systemic source; therefore, a high index of suspicion is needed to identify this disease.

Bilateral Proliferative Retinopathy as the Initial Presentation of Atypical Hemolytic Uremic Syndrome: A Case Report.

In this case report, we describe a 34-year-old male patient who presented with vision loss and was found to have profound occlusive retinal vasculopathy. His initial laboratory studies were unremarkable, but five weeks after his ocular symptoms began, he developed acute multi-organ failure and was ultimately diagnosed with atypical hemolytic uremic syndrome (aHUS). His course was complicated by a stroke, respiratory distress requiring intubation, long-term hemodialysis, and eventually death. Occlusive retinal vasculopathy may be the presenting finding in aHUS, although thrombotic microangiopathy syndromes typically present with acute kidney injury and or failure, hemolytic anemia, and thrombocytopenia. [Ophthalmic Surg Lasers Imaging Retina 2023;54:297-300.].

Comparison of Biometry Measurements Using Standard Partial Coherence Interferometry versus New Scheimpflug Tomography with Integrated Axial Length Capability.

PURPOSE: To compare biometry measurements obtained by a partial interferometer biometer (IOLMaster 500) to the new Scheimpflug tomography with an integrated axial length biometer module (Pentacam AXL). PATIENTS AND METHODS: Cataract patients who underwent biometric measurements with the IOL Master 500 and the Pentacam AXL from July to November 2017 were enrolled in this study. Comparisons were performed for axial length (AL), keratometry (K), and anterior chamber depth (ACD). The Pearson correlation coefficient and the 95% limits of agreement (LoA) were calculated. Paired Student's t-tests and Bland-Altman plots were used to assess the differences between devices. RESULTS: One hundred and sixty-six eyes of 92 patients were analyzed. There were no statistically significant differences in AL (p=0.558) or flat K (p=0.196) values between the IOL Master 500 and Pentacam AXL measurements. Statistically significant differences were found between the two devices with respect to steep K, ACD, and mean K measurements (p<0.001). CONCLUSION: Both devices provided similar measurements of AL and flat K, though there were statistically significant differences in ACD, steep K, and mean K measurements.

Objective evaluation of vision quality in pseudophakic patients with posterior capsular opacification using double-pass retinal imaging / Avaliação objetiva da qualidade da visão em pacientes pseudofácicos com opacificação capsular posterior pelo método de dupla passagem de luz

ABSTRACT Purpose: The purpose of this study was to objectively assess the optical vision quality of patients before and after Nd:YAG capsulotomy for posterior capsular opacification using a double-pass retinal imaging system. Methods: We retrospectively analyzed the data from 26 pseudophakic eyes with posterior capsular opacification that underwent Nd:YAG capsulotomy. The objective scatter indices, modulation transfer function cutoff frequencies, Strehl ratios, and logMAR corrected distance visual acuities were assessed before and after YAG capsulotomy with a double-pass retinal imaging system (OQAS II, Visiometrics, Spain). We also analyzed data from a subgroup of 10 patients with pre-YAG corrected distance visual acuity of 0.10 logMAR (20/25) or better. Results: Vision quality indices improved in all 26 eyes, resulting in a statistically significant improvement in the corrected distance visual acuity (p=0.007), objective scatter index (p=0.001), modulation transfer function cutoff frequency (p=0.001), and Strehl ratio (p=0.020). The overall mean improvements included 0.12 ± 0.04 logMAR for corrected distance visual acuity, 2.84 ± 0.76 for objective scatter index, 12.29 ± 2.77 for modulation transfer function cutoff frequency, and 0.06 ± 0.03 for Strehl ratio. Our sub-analysis of 10 eyes with 0.10 logMAR (20/25) corrected distance visual acuity or better also showed a statistically significant improvement in the mean objective scatter index (0.76 ± 16; p=0.001), resulting in approximately 35% decrease in intraocular light scatter. Conclusions: The objective vision quality measurements as assessed by the double-pass retinal imaging system showed a significant improvement after YAG capsulotomy. This suggests that the objective scatter index improves after YAG capsulotomy, even in eyes with pre-YAG 0.10 logMAR (Snellen 20/25) corrected distance visual acuity or better.

RESUMO Objetivo: Avaliar objetivamente a qualidade da visão óptica antes e depois da capsulotomia com Nd: YAG, obtida por imagem pelo metodo de dupla passagem de luz em pacientes com opacificação capsular posterior. Método: Análise retrospectiva de 26 olhos pseudofácicos com opacificação capsular posterior visualmente significativa, que foram submetidos à capsulotomia de Nd: YAG. O índice de dispersão objetiva, a função de transferência de modulação, a relação de Strehl e a acuidade visual à distância corrigida foram avaliados antes e após a capsulotomia com YAG usando o dupla passagem de luz (OQAS II, Visiometrics, Espanha). Também foi analisado um subgrupo de pacientes com acuidade visual à distância corrigida pré-YAG de 0,10 logMAR (20/25) ou melhor. Resultados: Os índices de qualidade da visão melhoraram em todos os 26 olhos, resultando em uma melhora estatisticamente significativa na acuidade visual à distância corrigida (p=0,007), índice de dispersão objetiva (p=0,001), função de transferência de modulação (p=0,001) e relação de Strehl (p=0,020). A melhora média na acuidade visual à distância corrigida foi de 0,12 ± 0,04 logMAR, no índice de dispersão objetiva foi de 2,84 ± 0,76, no função de transferência de modulação foi de 12,29 ± 2,77 e na razão de Strehl foi de 0,06 ± 0,03 em todos os olhos. Sub-análise de 10 olhos com 0.10 logMAR (20/25) acuidade visual à distância corrigida ou melhor também mostrou uma melhora estatisticamente significativa no índice de dispersão objetiva (p=0,001). A melhora média no OSI foi de 0,76 ± 16, uma diminuição de 35% na dispersão da luz intraocular. Conclusões: A qualidade da visão avaliada pelo dupla passagem de luz mostra uma melhora significativa nas medidas objetivas da qualidade da visão após a capsulotomia do YAG. O índice de dispersão objetiva melhora após a capsulotomia YAG, mesmo em olhos com acuidade visual à distância corrigida pré-YAG de 0,10 logMAR (Snellen 20/25) ou melhor.

A Model to Predict Postoperative Axial Length in Children Undergoing Bilateral Cataract Surgery With Primary Intraocular Lens Implantation.

PURPOSE: To develop a model for predicting postoperative globe axial length (AL) in children undergoing bilateral cataract surgery with primary intraocular lens (IOL) implantation in children older than 2 years. DESIGN: Retrospective case series. METHODS: Children were included only if AL data were available for both eyes before surgery and at least 1 year after surgery. We analyzed variables that could influence globe axial growth and developed a multivariable generalized estimating equation regression model to predict postoperative AL. RESULTS: Sixty-four children were included. The median age at surgery and at follow-up was 5.1 and 12.5 years, respectively. AL measurements were obtained in both eyes during 242 visits. The median AL before and at last follow-up was 22.2 and 23.1 mm, respectively. Beta value for the final model to predict postoperative AL is as below: intercept (1.93), preoperative AL (0.91), age at cataract surgery (-0.07), age at follow-up (0.14), and interaction between age at surgery and age at follow-up (-0.005). Using this model, for a hypothetical patient operated at 2.5 years of age with a 20.5 mm AL would be estimated to have a 22.8 mm AL at 18 years of age. CONCLUSION: IOL power selection is a major challenge of pediatric cataract surgery attributable to unpredictable future eye growth. This model theoretically could be used to predict individual future adult size AL for each child undergoing cataract surgery, helping the surgeon to customize the selection of an IOL power at implantation and also to help the parents understand what to expect.

Objective evaluation of vision quality in pseudophakic patients with posterior capsular opacification using double-pass retinal imaging.

PURPOSE: The purpose of this study was to objectively assess the optical vision quality of patients before and after Nd:YAG capsulotomy for posterior capsular opacification using a double-pass retinal imaging system. METHODS: We retrospectively analyzed the data from 26 pseudophakic eyes with posterior capsular opacification that underwent Nd:YAG capsulotomy. The objective scatter indices, modulation transfer function cutoff frequencies, Strehl ratios, and logMAR corrected distance visual acuities were assessed before and after YAG capsulotomy with a double-pass retinal imaging system (OQAS II, Visiometrics, Spain). We also analyzed data from a subgroup of 10 patients with pre-YAG corrected distance visual acuity of 0.10 logMAR (20/25) or better. RESULTS: Vision quality indices improved in all 26 eyes, resulting in a statistically significant improvement in the corrected distance visual acuity (p=0.007), objective scatter index (p=0.001), modulation transfer function cutoff frequency (p=0.001), and Strehl ratio (p=0.020). The overall mean improvements included 0.12 ± 0.04 logMAR for corrected distance visual acuity, 2.84 ± 0.76 for objective scatter index, 12.29 ± 2.77 for modulation transfer function cutoff frequency, and 0.06 ± 0.03 for Strehl ratio. Our sub-analysis of 10 eyes with 0.10 logMAR (20/25) corrected distance visual acuity or better also showed a statistically significant improvement in the mean objective scatter index (0.76 ± 16; p=0.001), resulting in approximately 35% decrease in intraocular light scatter. CONCLUSIONS: The objective vision quality measurements as assessed by the double-pass retinal imaging system showed a significant improvement after YAG capsulotomy. This suggests that the objective scatter index improves after YAG capsulotomy, even in eyes with pre-YAG 0.10 logMAR (Snellen 20/25) corrected distance visual acuity or better.

Translational inhibition of APP by Posiphen: Efficacy, pharmacodynamics, and pharmacokinetics in the APP/PS1 mouse.

INTRODUCTION: Translational inhibition of amyloid precursor protein (APP) by Posiphen has been shown to reduce APP and its fragments in cell culture, animal models, and mildly cognitively impaired patients, making it a promising drug candidate for the treatment of Alzheimer's disease. METHODS: We used a mouse model of Alzheimer's disease (APP/presenilin-1) to examine Posiphen's efficacy, pharmacodynamics, and pharmacokinetics. RESULTS: Posiphen treatment normalized impairments in spatial working memory, contextual fear learning, and synaptic function in APP/presenilin-1 mice, without affecting their visual acuity, motor skills, or motivation and without affecting wild-type mice. Posiphen had a prolonged effect in reducing APP and all related peptides for at least 9 hours after the last dose. Its concentration was higher in the brain than in plasma, and the most abundant metabolite was N8-norPosiphen. DISCUSSION: This is the first study demonstrating the therapeutic efficacy of inhibiting the translation of APP and its fragments in an Alzheimer's disease model.

Evidence of a novel mechanism for partial γ-secretase inhibition induced paradoxical increase in secreted amyloid ß protein.

BACE1 (ß-secretase) and α-secretase cleave the Alzheimer's amyloid ß protein (Aß) precursor (APP) to C-terminal fragments of 99 aa (CTFß) and 83 aa (CTFα), respectively, which are further cleaved by γ-secretase to eventually secrete Aß and Aα (a.k.a. P3) that terminate predominantly at residues 40 and 42. A number of γ-secretase inhibitors (GSIs), such as N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), have been developed with the goal of reducing Aß to treat Alzheimer's disease (AD). Although most studies show that DAPT inhibits Aß in a dose-dependent manner several studies have also detected a biphasic effect with an unexpected increase at low doses of DAPT in cell cultures, animal models and clinical trials. In this article, we confirm the increase in Aß40 and Aß42 in SH-SY5Y human neuroblastoma cells treated with low doses of DAPT and identify one of the mechanisms for this paradox. We studied the pathway by first demonstrating that stimulation of Aß, a product of γ-secretase, was accompanied by a parallel increase of its substrate CTFß, thereby demonstrating that the inhibitor was not anomalously stimulating enzyme activity at low levels. Secondly, we have demonstrated that inhibition of an Aß degrading activity, endothelin converting enzyme (ECE), yielded more Aß, but abolished the DAPT-induced stimulation. Finally, we have demonstrated that Aα, which is generated in the secretory pathway before endocytosis, is not subject to the DAPT-mediated stimulation. We therefore conclude that impairment of γ-secretase can paradoxically increase Aß by transiently skirting Aß degradation in the endosome. This study adds to the growing body of literature suggesting that preserving γ-secretase activity, rather than inhibiting it, is important for prevention of neurodegeneration.

Targets for AD treatment: conflicting messages from γ-secretase inhibitors.

Current evidence suggests that Alzheimer's disease (AD) is a multi-factorial disease that starts with accumulation of multiple proteins. We have previously proposed that inhibition of γ-secretase may impair membrane recycling causing neurodegeneration starting at synapses (Sambamurti K., Suram A., Venugopal C., Prakasam A., Zhou Y., Lahiri D. K. and Greig N. H. A partial failure of membrane protein turnover may cause Alzheimer's disease: a new hypothesis. Curr. Alzheimer Res., 3, 2006, 81). We also proposed familal AD mutations increase Aß42 by inhibiting γ-secretase. Herein, we discuss the failure of Eli Lilly's γ-secretase inhibitor, semagacestat, in clinical trials in the light of our hypothesis, which extends the problem beyond toxicity of Aß aggregates. We elaborate that γ-secretase inhibitors lead to accumulation of amyloid precursor protein C-terminal fragments that can later be processed by γ-secretase to yields bursts of Aß to facilitate aggregation. Although we do not exclude a role for toxic Aß aggregates, inhibition of γ-secretase can affect numerous substrates other than amyloid precursor protein to affect multiple pathways and the combined accumulation of multiple peptides in the membrane may impair its function and turnover. Taken together, protein processing and turnover pathways play an important role in maintaining cellular homeostasis and unless we clearly see consistent disease-related increase in their levels or activity, we need to focus on preserving their function rather than inhibiting them for treatment of AD and similar diseases.