Acute posterior multifocal placoid pigment epitheliopathy: clinical presentation and risk of stroke and transient ischaemic attack.

BACKGROUND/AIMS: Acute posterior multifocal placoid pigment epitheliopathy is a rare but important disease that can be associated with life-threatening complications due to cerebral vasculitis. The primary objective was to determine the incidence of neurological complications and risk factors for stroke and transient ischaemic attack (TIA) associated with acute posterior multifocal placoid pigment epitheliopathy. Secondary objectives included the clinical presentation, visual outcomes and recurrence rates. METHODS: This was a multicentre retrospective case series including 111 eyes from 60 subjects presenting from January 2009 to June 2020. RESULTS: Median age at presentation was 29 years (IQR 24.7-35.1) and 36 subjects (60.0%) were male. 20 subjects (33.3%) reported a viral prodrome. Stroke and TIA were observed in seven subjects (11.7%). Older age was the only significant risk factor for stroke/TIA (p=0.042). Vision loss occurred in seven eyes, with four eyes (3.6%) having final visual acuity 6/15-6/60 and three eyes (2.7%) having visual acuity of 6/60 or worse. Recurrence occurred in 10 subjects (16.7%). CONCLUSIONS: The presence of headache cannot reliably predict those at risk of stroke/TIA. Individuals presenting with acute posterior multifocal pigment epitheliopathy should therefore undergo a clinical neurological review and work-up for cerebral vasculitis as deemed appropriate by the treating ophthalmologist and collaborating neurologist.

A 20-year multicentre retrospective review of optic nerve sheath fenestration outcomes.

Background: Optic nerve sheath fenestration (ONSF) longitudinal outcomes remain unclear and are vital in the assessment of vision failure in patients with raised intracranial pressure (ICP). Furthermore, limited observational data exists regarding its use in other causes of raised ICP. Objective: To determine the efficacy and safety of ONSF for idiopathic intracranial hypertension (IIH), cerebral venous sinus thrombosis (CVST), and other indications. Method: Multicentre study from a tertiary hospital and specialty eye referral hospital in Melbourne, Australia, from July 2000 to December 2020. A total of 116 eyes from 70 patients undergoing ONSF were retrospectively reviewed with patient demographics, surgery indications, visual acuity (VA), visual fields, fundus photos of optic discs, retinal nerve fibre layer (RNFL) thickness, average thickness of optic discs on optical coherence tomography (OCT), and complications recorded. Parametric tests were used to compare the treatment groups pre- and post-operatively. Results: A total of 116 eyes from 70 patients underwent ONSF, which involved 92 eyes with IIH, 9 eyes with CVST, and 15 eyes with other aetiologies ('Other'). Post ONSF, there was a best corrected visual acuity (BCVA) improvement or stabilisation in 84% of patients in all groups, with 50% achieving a BCVA of 6/6 or better at the final follow-up. RNFL, visual fields, and fundus grades all trended towards improvement, with most improvement noted by day 360. Common complications included transient diplopia (n = 29, 25%) and worsening of visual function requiring further cerebrospinal fluid (CSF) diversion procedures (n = 20, 17%). Complications were most significant in the 'Other' group with 1/3 of eyes requiring further CSF diversion procedures. Conclusion: Our data demonstrates effectiveness in the use of ONSF in papilloedema with visual failure due to IIH or CVST and when other CSF diversion procedures or medical therapies have failed.

A Case of Pulmonary Nodular Lymphoid Hyperplasia Responding to Corticosteroid Treatment.

Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare non-neoplastic disease that presents with mass lesions in the lung. It is radiologically difficult to differentiate it from adenocarcinoma of the lung or pulmonary lymphoma. There has been no consensus regarding the treatment of PNLH; however, in many case series, patients usually undergo surgical resection for diagnostic and therapeutic purposes. Here, we present the case of a 60-year-old Chinese male who presented with cough and hemoptysis. A computed tomography scan of the thorax revealed a mass-like lesion. A biopsy was performed which showed lymphocytic pneumonitis. He was treated with a tapering dose of corticosteroids with good clinical and radiological outcomes. Upon a subsequent review of the case, a diagnosis of PNLH was made. This case report suggests that corticosteroids may be an alternative therapy to surgical resection. They have the advantage of being non-invasive and can be used in patients who are otherwise not surgical candidates due to other comorbidities. However, further research is required before we can recommend corticosteroids as a treatment for PNLH.

Ibrutinib-related uveitis: A case series.

PURPOSE: Four cases of ibrutinib-related uveitis are presented, which are to the best of our knowledge the first in the literature. Possible mechanisms of ibrutinib-mediated uveitis are explored. OBSERVATIONS: Case 1 is a 60-year-old female who had been stable on 1 year of ibrutinib for chronic lymphocytic leukaemia. She was diagnosed with ibrutinib-related uveitis, which responded well to topical steroids. Case 2 is a 63-year-old male diagnosed with uveitis after 2 years of ibrutinib treatment for chronic lymphocytic leukaemia. He responded well to topical and oral steroids; however, he continued to have uveitis relapses after weaning steroids. Case 3 is a 69-year-old male diagnosed with uveitis after 18 months of ibrutinib treatment. He was trialed on topical and intravenous steroids, and restarted ibrutinib without worsening of symptoms. Case 4 is a 66-year-old female who developed uveitis after being stable on ibrutinib for 3 years. She responded well to topical steroids. CONCLUSIONS AND IMPORTANCE: Inflammatory complications of tyrosine kinase inhibitors are well described. While ibrutinib, and other kinase inhibitors, are generally well-tolerated, there are increasing reports of ocular toxicities, including uveitis. It is recommended to monitor patients for potential ocular adverse effects and facilitate rapid ophthalmologic assessment.

Enhanced Performance of Polymer Electrolyte Membranes via Modification with Ionic Liquids for Fuel Cell Applications.

The polymer electrolyte membrane (PEM) is a key component in the PEM fuel cell (PEMFC) system. This study highlights the latest development of PEM technology by combining Nafion® and ionic liquids, namely 2-Hydroxyethylammonium Formate (2-HEAF) and Propylammonium Nitrate (PAN). Test membranes were prepared using the casting technique. The impact of functional groups in grafting, morphology, thermal stability, ion exchange capacity, water absorption, swelling and proton conductivity for the prepared membranes is discussed. Both hybrid membranes showed higher values in ion exchange capacity, water uptake and swelling rate as compared to the recast pure Nafion® membrane. The results also show that the proton conductivity of Nafion®/2-HEAF and Nafion®/PAN membranes increased with increasing ionic liquid concentrations. The maximum values of proton conductivity for Nafion®/2-HEAF and Nafion®/PAN membranes were 2.87 and 4.55 mScm-1, respectively, equivalent to 2.2 and 3.5 times that of the pure recast Nafion® membrane.

HMG-CoA reductase expression in human eyelid tissue and in a human meibomian gland epithelial cell line.

PURPOSE: 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of cholesterol production, has been found to contribute to lipid secretion from skin sebaceous glands and hair follicles. We assessed for HMGCR expression in human eyelid tissue and in immortalized human meibomian gland epithelial cells (HMGECs) using immunohistochemistry. METHODS: Full thickness human eyelid specimens in archival paraffin blocks were obtained. A section from each block was stained with hematoxylin and eosin and examined by an ocular pathologist for validation of tissue pathology. Immunohistochemistry was performed using rabbit anti-human HMGCR antibody on serial sections using the Ventana automated staining system. HMGCR expression was examined for in HMEGCs with fluorescence immunocytochemistry and confocal microscopy. RESULTS: Thirteen full thickness eyelid specimens met the inclusion criteria. All specimens contained meibomian glands, and 2 (15%) contained glands of Zeis, 3 (23%) pilosebaceous glands, 2 (15%), accessory lacrimal glands, and 2 (15%), glands of Moll, respectively. Immunohistochemistry showed HMGCR expression in meibocytes of meibomian glands and sebocytes of Zeis and pilosebaceous glands in all specimens. HMGCR expression was also evident in vascular endothelium. Immunofluorescence was positive for HMGCR expression on HMGEC cells. No labeling was seen for the negative Ig control. CONCLUSION: HMGCR was expressed in all eyelid sebaceous-type glands and in HMGECs, consistent with a role for cholesterol production in the genesis of tear film lipids. The observed expression also provides a rationale for using topical statins, inhibitors of HMGCR, as novel tear film lipid stabilizers in conditions such as blepharitis, where meibum production is aberrant.

Measurement of Retinal Sensitivity on Tablet Devices in Age-Related Macular Degeneration.

PURPOSE: We compared measurements of central retinal sensitivity on a portable, low-cost tablet device to the established method of microperimetry in age-related macular degeneration (AMD). METHODS: A customized test designed to measure central retinal sensitivity (within the central 1° radius) on a tablet device was developed using an open-source platform called PsyPad. A total of 30 participants with AMD were included in this study, and all participants performed a practice test on PsyPad, followed by four tests of one eye and one test of the other eye. Participants then underwent standardized microperimetry examinations in both eyes. RESULTS: The average test duration on PsyPad was 53.9 ± 7.5 seconds, and no significant learning effect was observed over the examinations performed (P = 1.000). The coefficient of repeatability of central retinal sensitivity between the first two examinations on PsyPad was ±1.76 dB. The mean central retinal sensitivity was not significantly different between PsyPad (25.7 ± 0.4 dB) and microperimetry (26.1 ± 0.4 dB, P = 0.094), and the 95% limits of agreement between the two measures were between -4.12 and 4.92 dB. CONCLUSIONS: The measurements of central retinal sensitivity can be performed effectively using a tablet device, displaying reasonably good agreement with those obtained using the established method of microperimetry. TRANSLATIONAL RELEVANCE: These findings highlight the potential of tablet devices as low-cost and portable tools for developing and performing visual function measures that can be easily and widely implemented.

Fundus autofluorescence characteristics of nascent geographic atrophy in age-related macular degeneration.

PURPOSE: We examined the fundus autofluorescence (FAF) characteristics of nascent geographic atrophy (nGA), pathological features preceding the development of drusen-associated atrophy in eyes with age-related macular degeneration (AMD) that can be visualized using high-resolution optical coherence tomography (OCT). METHODS: Spectral-domain OCT (SD-OCT) and FAF imaging were performed longitudinally in 221 eyes with intermediate AMD (having at least drusen >125 µm), and seven areas that developed drusen-associated atrophy in five eyes were examined and categorized with respect to FAF characteristics. These categories then were used to characterize 49 areas of nGA or drusen-associated atrophy on SD-OCT identified in a cross-sectional study with 230 participants with bilateral intermediate AMD. RESULTS: Sequential imaging revealed that FAF characteristics in the atrophic areas could be grouped into three categories: predominantly hyperautofluorescent (hyperAF), presence of both hyper- and hypoautofluorescence (mixed AF), or predominantly hypoautofluorescent (hypoAF). In the cross-sectional study, the FAF characteristics were significantly dependent on the type of atrophic area (P = 0.002), where areas of nGA appeared most commonly as being mixed AF (63%), while areas of drusen-associated atrophy most commonly as hypoAF (86%). CONCLUSIONS: Fundus autofluorescence imaging revealed that areas of nGA were most commonly characterized by both hyper- and hypoautofluorescent changes, which differs from areas of drusen-associated atrophy that most often appeared hypoautofluorescent. These findings provide important insights into the FAF characteristics of areas undergoing atrophic changes in eyes still considered to be in the early stages of AMD by current methods, and thus assist in the characterization of disease severity in these early stages.

Optical coherence tomography-defined changes preceding the development of drusen-associated atrophy in age-related macular degeneration.

PURPOSE: To characterize the pathological changes preceding the development of drusen-associated atrophy in eyes with age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Longitudinal and cross-sectional retrospective observational study. PARTICIPANTS: A total of 181 participants with intermediate AMD in at least 1 eye (141 unilateral, 40 bilateral) were assessed longitudinally. A total of 230 participants with bilateral intermediate AMD (40 longitudinal participants with an additional 190 participants) were analyzed cross-sectionally. METHODS: Spectral-domain OCT, color fundus photography (CFP), near-infrared reflectance, and fundus autofluorescence imaging were performed in all participants at cross-section and every 3 months for up to 30 months in the longitudinal study. Spectral-domain OCT volume scans were examined for features that portend the development of drusen-associated atrophy, and the topography, prevalence, and risk factors of these features were determined through cross-sectional analysis. MAIN OUTCOME MEASURES: The pathological features on SD-OCT preceding the development of drusen-associated atrophy and the characteristics of these features. RESULTS: Twenty areas from 16 eyes of 16 participants developed drusen-associated atrophy after an average of 20 months (range, 8-30 months). Spectral-domain OCT features unique in these areas included: subsidence of the outer plexiform layer (OPL) and inner nuclear layer (INL), and development of a hyporeflective wedge-shaped band within the limits of the OPL. These characteristics were termed "nascent geographic atrophy" (nGA), describing features that portend the development of drusen-associated atrophy. Cross-sectional examination of participants with bilateral intermediate AMD revealed that independent risk factors for the presence of nGA included the presence of pigmentary changes (odds ratio [OR], 16.84; 95% confidence interval [CI], 2.42-117.24) and nGA in the fellow eye (OR, 4.15; 95% CI, 1.12-15.34); nGA was present in 21.9% of participants with drusen >125 µm and pigmentary changes in both eyes. CONCLUSIONS: This study identified pathological changes occurring before the development of drusen-associated atrophy using SD-OCT, which we defined as nGA. Although nGA is undetectable on CFP, it is important for determining the risk of future vision loss in AMD and could be used as an earlier surrogate end point in interventional trials targeting the early stages of AMD.

The reading of components of diabetic retinopathy: an evolutionary approach for filtering normal digital fundus imaging in screening and population based studies.

In any diabetic retinopathy screening program, about two-thirds of patients have no retinopathy. However, on average, it takes a human expert about one and a half times longer to decide an image is normal than to recognize an abnormal case with obvious features. In this work, we present an automated system for filtering out normal cases to facilitate a more effective use of grading time. The key aim with any such tool is to achieve high sensitivity and specificity to ensure patients' safety and service efficiency. There are many challenges to overcome, given the variation of images and characteristics to identify. The system combines computed evidence obtained from various processing stages, including segmentation of candidate regions, classification and contextual analysis through Hidden Markov Models. Furthermore, evolutionary algorithms are employed to optimize the Hidden Markov Models, feature selection and heterogeneous ensemble classifiers. In order to evaluate its capability of identifying normal images across diverse populations, a population-oriented study was undertaken comparing the software's output to grading by humans. In addition, population based studies collect large numbers of images on subjects expected to have no abnormality. These studies expect timely and cost-effective grading. Altogether 9954 previously unseen images taken from various populations were tested. All test images were masked so the automated system had not been exposed to them before. This system was trained using image subregions taken from about 400 sample images. Sensitivities of 92.2% and specificities of 90.4% were achieved varying between populations and population clusters. Of all images the automated system decided to be normal, 98.2% were true normal when compared to the manual grading results. These results demonstrate scalability and strong potential of such an integrated computational intelligence system as an effective tool to assist a grading service.

Identification of urinary biomarkers for age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) can be considered as a chronic low-grade systemic inflammatory disease. This study was undertaken to test the associations of AMD with the urinary proinflammatory cytokines transforming growth factor (TGF)-ß1, macrophage chemoattractant protein (MCP)-1 and C3a-desArg, as potential noninvasive biomarkers for monitoring AMD. METHODS: A cross-sectional study of 103 AMD cases, comprising early AMD (n = 51), geographic atrophy (GA; n = 19), or choroidal neovascularization (CNV; 33), and 54 unrelated controls, aged 73 ± 9 years, who attended the Royal Victorian Eye and Ear Hospital and private practice in Victoria, Australia. AMD status was determined from the bilateral retinal digital photographs and through angiography and optical coherence tomography images when confirmation of CNV was needed. Serum and urine cytokine levels were measured by immunoassay and the rs1061170 (Y402H) single-nucleotide polymorphism of the complement factor H (CFH) gene was determined. RESULTS: Multivariate logistic regression analyses demonstrated significant associations of urinary TGF-ß1 levels (odds ratio [95% confidence interval]: OR = 1.24 [1.02-1.50]; P < 0.031) and MCP-1 levels (OR = 1.07 [1.02-1.12]; P < 0.008), in early AMD, and also MCP-1 levels with GA (OR = 1.10 [1.03-1.17]; P < 0.003). There was no correlation between urinary and serum cytokine levels. Individuals with one or more copies of the C allele (Y402H) were 2.5 times more likely to have urinary MCP-1 above median levels (P < 0.040). CONCLUSIONS: This study demonstrates a novel finding of an association between elevated urinary cytokines TGF-ß1 and MCP-1 and AMD. Further development of a urinary biomarker profile could provide a practical tool for detection of early AMD, progression monitoring, and assessment of treatment efficacy.