Cardiovascular Disease Predicts Structural and Functional Progression in Early Glaucoma.

PURPOSE: To investigate the association between cardiovascular disease and baseline structural defects and disease progression in glaucoma. DESIGN: Prospective, longitudinal study of preperimetric and perimetric glaucoma. PARTICIPANTS: Two thousand six hundred twenty-eight eyes from 1314 participants recruited to the Progression Risk of Glaucoma: Relevant SNPs with Significant Association (PROGRESSA) study were evaluated for baseline and longitudinal structural thinning using spectral-domain OCT and for visual field progression on Humphrey visual field (HVF) assessment. METHODS: Patients were classified as either predominantly macula ganglion cell-inner plexiform layer (mGCIPL), predominantly peripapillary retinal nerve fiber layer (pRNFL), or both mGCIPL and pRNFL structural change at enrollment, and then evaluated for longitudinal OCT or HVF progression. Cardiovascular disease and medication characteristics of the participants were compared with a reference group of stable patients. MAIN OUTCOME MEASURES: OCT and HVF baseline status and longitudinal progression. RESULTS: After accounting for age and cardiovascular characteristics, patients with predominantly mGCIPL thinning at baseline showed a higher prevalence of hypertension (odds ratio [OR], 2.70; 95% confidence interval [CI], 1.66-4.41; P < 0.001), antihypertensive use (OR, 2.03; 95% CI, 1.20-3.46; P = 0.008), and statin use (OR, 1.98; 95% CI, 1.07-3.66; P = 0.029) than reference patients. Patients with predominantly pRNFL thinning exhibited a comparable prevalence of cardiovascular disease or medication with reference patients. Review of longitudinal OCT and HVF data (mean follow-up, 5.34 ± 1.29 years) showed that hypertension was associated with an increased risk of both OCT (OR, 1.79; 95% CI, 1.17-2.75; P = 0.006) and HVF progression (OR, 1.92; 95% CI, 1.18-3.15; P = 0.013). A 1-standard deviation (approximately 21 mmHg) increase in systolic blood pressure at baseline was associated with a greater risk of OCT progression (OR, 1.27; 95% CI, 1.01-1.63; P = 0.041) and HVF progression (OR, 1.32; 95% CI, 1.01-1.73; P = 0.043). The association between systolic blood pressure and structural progression was comparable to that observed between intraocular pressure and structural progression (OR, 1.30; 95% CI, 1.01-1.67; P = 0.039). CONCLUSIONS: Cardiovascular disease is an important risk factor for glaucoma progression.

Macular Ganglion Cell-Inner Plexiform Layer Loss Precedes Peripapillary Retinal Nerve Fiber Layer Loss in Glaucoma with Lower Intraocular Pressure.

PURPOSE: To investigate which clinical measures influence whether an individual demonstrates earliest glaucomatous structural progression on peripapillary retinal nerve fiber layer (pRNFL) or macular ganglion cell-inner plexiform layer (mGCIPL). DESIGN: Prospective, longitudinal cohort study. PARTICIPANTS: Two hundred seventy-one eyes from 207 individuals with statistically significant evidence of glaucomatous progression on OCT Guided Progression Analysis (GPA) software were drawn from a total of 1271 eyes from 686 individuals categorized as glaucoma suspect or having early manifest glaucoma undergoing glaucoma surveillance. METHODS: Individuals demonstrating earliest evidence of longitudinal progression on mGCIPL GPA event analysis were compared with individuals demonstrating evidence of earliest longitudinal progression on pRNFL GPA event analysis. MAIN OUTCOME MEASURES: Correlation of OCT event change analysis with intraocular pressure (IOP), clinical variables, and baseline thickness of the pRNFL and mGCIPL. RESULTS: Intraocular pressure, baseline pRNFL thickness, baseline mGCIPL thickness, and systemic hypertension were associated with location of first progression. Eyes demonstrating earliest longitudinal progression on mGCIPL had significantly lower maximum-recorded pretreatment IOP (mean difference, 3.90 mmHg; 95% confidence interval [CI], 2.37-5.43 mmHg; P < 0.001). The interval between progression on pRNFL and progression on mGCIPL increased by 12.4 months for every 5-mmHg increase in IOP (95% CI, 10.32-15.72 months). Eyes demonstrating earliest longitudinal progression on mGCIPL showed significantly lower baseline average pRNFL thickness than eyes progressing on pRNFL first (mean difference, 7.07 µm; 95% CI, 4.38-9.77 µm; P < 0.001). Eyes progressing first on mGCIPL parameters were 3.03 times more likely to demonstrate a new paracentral field defect than eyes progressing first on pRNFL parameters (odds ratio, 3.03; 95% CI, 1.26-7.28; P = 0.01). CONCLUSIONS: Clinical features, particularly pretreatment IOP, influence whether structural glaucoma progression is detected earlier with mGCIPL or pRNFL imaging. These data support the usefulness of mGCIPL imaging in addition to pRNFL analysis for detection of glaucoma progression, particularly in patients with normal IOP.

Changes in Australian practice patterns for glaucoma management.

IMPORTANCE: The demand for glaucoma care is projected to increase significantly with the ageing population. BACKGROUND: To characterize trends in Australian practice patterns for glaucoma management over the 15-y period between 2003 and 2017. DESIGN: Retrospective audit. SAMPLES: The Medicare eligible population. METHODS: Audit of Medicare Benefits Schedule item number reimbursements in the private healthcare sector, and dispensed Pharmaceutical Benefits Scheme (PBS) prescriptions. MAIN OUTCOME MEASURES: Number, unadjusted cost and services per capita in the enrolled population. RESULTS: The number of medication prescriptions peaked in 2015, but then declined by 14.9%. PBS expenditure on glaucoma medications has been falling since 2012. There was a 9.2-fold increase in fixed-combination prescriptions and 281-fold increase in unpreserved medication prescriptions. In 2017, optometrists generated 1.86% of glaucoma prescriptions. Reimbursements for computerized perimetry increased dramatically for optometrists, and in 2017 optometrist-initiated perimetry exceeded ophthalmologist-initiated perimetry by 35.3%. There were significant increases in laser procedure rates, including laser trabeculoplasty (4.61-fold), laser iridotomy (2.55-fold) and cyclodestructive procedures (2.33-fold). There was a 3.83-fold increase in glaucoma drainage device insertions. Ab interno trabecular microbypass procedures increased 715% from 2014 to 2017. Adjusted for Medicare population, trabecular microbypass is performed at more than twice the rate of primary filtering operations. CONCLUSIONS AND RELEVANCE: This is the first time that glaucoma medication use and expenditure have declined since auditing began in 1992. Glaucoma laser procedures, drainage device implantation and trabecular microbypass increased substantially over the study period. In contrast, the rate of primary filtering operations increased in proportion to population growth. The increase in overall cost of glaucoma care has primarily been driven by computerized perimetry; however, this has been partially offset by a decline in medication expenditure.

Review of the association between retinal microvascular characteristics and eye disease.

Computerized retinal imaging technologies enable the static and dynamic measurement of a range of retinal microvascular parameters. Large population-based studies have reported associations between these microvascular indices and various ophthalmic diseases including diabetes, age-related macular degeneration, retinal artery embolism, retinal vein occlusion, glaucoma and non-glaucomatous optic neuropathies. Increasingly, sophisticated imaging and analysis techniques have the potential to provide relevant clinical information regarding disease risk and progression; however, further studies are required to verify associations and strengthen the predictive power of these techniques. We summarize the current state of knowledge regarding retinal microvascular characteristics and eye disease.

Review of paediatric retinal microvascular changes as a predictor of cardiovascular disease.

Recent studies have supported the hypothesis that exposure to established cardiovascular risk factors in early life predisposes to the development of adult cardiovascular disease. Retinal imaging is an emerging technique which facilitates non-invasive, accurate and reproducible assessment of the retinal microvasculature. The assessment may be in the form of static vascular calibre measurements and assessment of the vascular geometry or dynamic structural and functional assessments. Paediatric retinal microvascular changes are reported in response to elevated blood pressure, type 1 diabetes, increasing adiposity, diet, physical activity, systemic inflammation, metabolic peptides, family history and prenatal factors. The resultant microvascular changes have been linked to sub-clinical and overt cardiovascular, cerebrovascular and metabolic disease states in the adult population. Still missing however is longitudinal evidence showing the persistence of retinal microvascular alterations into adulthood. Future studies will enable retinal microvascular assessment to further evaluate the pathogenesis of disease states and response to intervention. The data obtained will also aid in expanding the clinical utility of retinal imaging as a cardiovascular risk prediction and monitoring tool and supplement existing recommendations to reduce cardiovascular morbidity and mortality.

Ten-year all-cause mortality and its association with vision among Indigenous Australians within Central Australia: the Central Australian Ocular Health Study.

BACKGROUND: No studies to date have explored the association of vision with mortality in Indigenous Australians. We aimed to determine the 10-year all-cause mortality and its associations among Indigenous Australians living in Central Australia. DESIGN: Prospective observational cohort study. PARTICIPANTS: A total of 1257 (93.0%) of 1347 patients from The Central Australian Ocular Health Study, over the age of 40 years, were available for follow-up during a 10-year period. METHODS: All-cause mortality and its associations with visual acuity, age and gender were analysed. MAIN OUTCOME MEASURES: All-cause mortality. RESULTS: All-cause mortality was 29.3% at the end of 10 years. Mortality increased as age of recruitment increased: 14.2% (40-49 years), 22.6% (50-59 years), 50.3% (60 years or older) (χ = 59.15; P < 0.00001). Gender was not associated with mortality as an unadjusted variable, but after adjustment with age and visual acuity, women were 17.0% less likely to die (t = 2.09; P = 0.037). Reduced visual acuity was associated with increased mortality rate (5% increased mortality per one line of reduced visual acuity; t = 4.74; P < 0.0001) after adjustment for age, sex, diabetes and hypertension. CONCLUSIONS: The 10-year all-cause mortality rate of Indigenous Australians over the age of 40 years and living in remote communities of Central Australia was 29.3%. This is more than double that of the Australian population as a whole. Mortality was significantly associated with visual acuity at recruitment. Further work designed to better understand this association is warranted and may help to reduce this disparity in the future.

IgG4 Staining in Thyroid Eye Disease.

IgG4-related ophthalmic disease is increasingly widely recognized. Moreover, IgG4 staining can occur in other inflammatory diseases. The authors report a case of IgG4 staining of an enlarged, inflamed levator palpebrae superioris in a patient with a past history of thyroid eye disease. A 78-year-old woman with quiescent hyperthyroidism had clinical and radiological evidence of levator palpebrae superioris inflammation without superior rectus involvement. A biopsy was consistent with IgG4-related ophthalmic disease. There was a marked but incomplete response to an orbital injection of triamcinolone. The authors discuss the association between thyroid eye disease and IgG4 staining and the diagnostic issues that arise when IgG4-related ophthalmic disease criteria are fulfilled in patients with other orbital inflammatory conditions.

Periocular Squamous Cell Carcinoma: TNM Staging and Recurrence.

PURPOSE: To analyze the TNM stage, management, and recurrence rates of patients with histologically confirmed squamous cell carcinoma (SCC) of the eyelid. DESIGN: Retrospective case series from 3 Australian centers. PARTICIPANTS: A total of 254 cases of eyelid SCC from 254 patients (median age, 73 years; range, 28-102 years; 159 were male). METHODS: Tumors were staged according to The American Joint Committee on Cancer 7th edition TNM criteria for eyelid carcinoma. MAIN OUTCOME MEASURES: Outcomes and recurrence rates according to TNM stage at presentation. RESULTS: A total of 25 cases (9.8%) were recurrent tumors. TNM classifications were as follows: T1N0M0, 74 patients (29.1%); T2aN0M0, 92 patients (36.2%); T2bN0M0, 50 patients (19.7%); T3aN0M0, 31 patients (12.2%); T3bN0M0, 5 patients (2.0%); T2bN0M1, 1 patient (0.4%); and T3bN1M1, 1 patient (0.4%). Perineural invasion (PNI) was present histologically in 8.3% of cases. Treatment modalities included Mohs microsurgery (31.1%), wide local excision (WLE) with paraffin section control (21.7%), WLE with frozen-section control (19.3%), and excision without margin control (24.4%). Three cases did not receive treatment. Median follow-up was 40 months (range, <1-132 months). Local recurrence occurred in 17 treated patients (6.8%). The recurrence rate was 5.3% (12/226 patients) for primary tumors and 20% (5/25 patients) for recurrent tumors (P = 0.019). Four patients (1.6%) died of their disease during follow-up. Higher T stage was significantly associated with both PNI (P = 0.035) and local recurrence (P < 0.001). We could not identify a T-stage threshold below which there was no risk of recurrence, as evidenced by 3 T1 primary tumors that recurred. CONCLUSIONS: Higher T stage was significantly associated with local recurrence, and recurrent tumors had a 4-fold increased risk of further recurrence compared with primary tumors. Therefore, it may be reasonable to consider sentinel lymph node biopsy or close nodal surveillance and follow-up for patients with recurrent or high T-stage tumors. Of note, we could not identify a T-stage threshold below which there was no risk of recurrences; therefore, clinicians should be aware of the potential for low T-stage tumors to recur.

IgG4-Related Ophthalmic Disease: Pooling of Published Cases and Literature Review.

In recent years, IgG4-related ophthalmic disease (IgG4-ROD) has emerged as a common cause of orbital inflammation, accounting for a substantial proportion of idiopathic orbital inflammation and lymphoid hyperplasia. The last pooled analysis of published cases was conducted in 2012, but a large number of new cases have been added to the literature since then. In this review, we present the demographic, clinical, histological, and treatment data for 172 published cases of biopsy-confirmed IgG4-ROD. Results are accompanied by a review of the relevant literature.

Review of 268 lacrimal gland biopsies in an Australian cohort.

BACKGROUND: To review the distribution of pathology in lacrimal gland biopsies performed in an Australian cohort. DESIGN: Retrospective review. PARTICIPANTS: Two hundred sixty-eight lacrimal gland biopsies from 263 patients. METHODS: Pathology archives in South Australia and Victoria were searched for lacrimal gland biopsies performed between 1 January 1997 and 31 December 2012. Data retrieved included the year of biopsy, the histopathological diagnosis, patient age and gender. MAIN OUTCOME MEASURES: Distribution of pathology affecting the lacrimal gland; patient age and gender. RESULTS: The distribution of lacrimal gland pathology was: inflammations and vasculitides 50.0%, lymphomas 19.8%, lymphoid hyperplasias 12.3%, benign epithelial tumours 7.8% (all pleomorphic adenomas), malignant epithelial tumours 4.1%, dacryops 3.0% and miscellaneous 3.0%. The mean age was 52 years, with lymphoma affecting the oldest patient group (64.6 years) and sarcoidosis the youngest (40.6 years). Of the patients with biopsy-confirmed dacryoadenitis, biopsy revealed a specific diagnosis in 34% of cases. Immunoglobulin G4-related disease was the most common 'specific' dacryoadenitis. Significantly more pleomorphic adenomas were diagnosed in the period 1997-2004 than the period 2005-2012 inclusive, but there were no other significant changes in the distribution of pathology over time. CONCLUSIONS: Two thirds of dacryoadenitis was 'non-specific', two thirds of epithelial tumours were pleomorphic adenomas and approximately two thirds of all lacrimal gland biopsies were accounted for by inflammations and lymphoid hyperplasias. The ratio of inflammations to neoplasias will be significantly influenced by the clinician's threshold for biopsying patients presenting with features of dacryoadenitis.

Improved artery-vein separation with acceleration-dependent preparation for non-contrast-enhanced magnetic resonance angiography.

PURPOSE: To compare the use of acceleration-dependent and velocity-dependent flow-preparation for non-contrast-enhanced magnetic resonance angiography (NCE-MRA), investigating both image quality and the ability to discriminate between arteries and veins. We develop an acceleration-dependent NCE-MRA method known as acceleration dependent vascular anatomy for non-contrast-enhanced MRA (ADVANCE-MRA). METHODS: Acceleration-dependent and velocity-dependent images were acquired using a constant and pulsatile flow-phantom and from the lower legs of six healthy volunteers and one patient with peripheral vascular disease. The volunteer images were assessed both by quantitative signal measurements and qualitative scoring by a radiologist. RESULTS: In the phantom, acceleration-dependent preparation depicted pulsatile but not constant flow, while velocity-dependent preparation depicted both. In the volunteers and the patient, the velocity-dependent preparation was unable to separate the arterial and venous signals completely, with some overlap of arterial and venous signals for all acquired flow sensitizations whereas the acceleration-dependent preparation gave complete artery-vein separation over a wide range of flow sensitizations. Acceleration-dependent preparation received the best overall qualitative scores for arterial image quality and venous contamination. CONCLUSION: Acceleration-dependent NCE-MRA improves arterial image quality and reduces venous contamination, compared with velocity-dependent NCE-MRA, and warrants further investigation in patients.

Determinants of neonatal mortality in Nigeria: evidence from the 2008 demographic and health survey.

BACKGROUND: Nigeria continues to have one of the highest rates of neonatal deaths in Africa. This study aimed to identify risk factors associated with neonatal death in Nigeria using the 2008 Nigeria Demographic and Health Survey (NDHS). METHODS: Neonatal deaths of all singleton live-born infants between 2003 and 2008 were extracted from the 2008 NDHS. The 2008 NDHS was a multi-stage cluster sample survey of 36,298 households. Of these households, survival information of 27,147 singleton live-borns was obtained, including 996 cases of neonatal mortality. The risk of death was adjusted for confounders relating to individual, household, and community level factors using Cox regression. RESULTS: Multivariable analyses indicated that a higher birth order of newborns with a short birth interval ≤ 2 years (hazard ratio [HR] = 2.19, confidence interval [CI]: 1.68-2.84) and newborns with a higher birth order with a longer birth interval > 2 years (HR = 1.36, CI: 1.05-1.78) were significantly associated with neonatal mortality. Other significant factors that affected neonatal deaths included neonates born to mothers younger than 20 years (HR = 4.07, CI: 2.83-5.86), neonates born to mothers residing in rural areas compared with urban residents (HR = 1.26, CI: 1.03-1.55), male neonates (HR = 1.30, CI: 1.12-1.53), mothers who perceived their neonate's body size to be smaller than the average size (HR = 2.10, CI: 1.77-2.50), and mothers who delivered their neonates by caesarean section (HR = 2.80, CI: 1.84-4.25). CONCLUSIONS: Our study suggests that the Nigerian government needs to invest more in the healthcare system to ensure quality care for women and newborns. Community-based intervention is also required and should focus on child spacing, childbearing at a younger age, and poverty eradication programs, particularly in rural areas, to reduce avoidable neonatal deaths in Nigeria.

Immunoglobulin G4-related disease of the hard palate.

A 71-year-old woman presented with erythematous, nontender, bilateral hard palate nodules of 6-month duration. Biopsy showed collagenous sclerosis and a follicular lymphoplasmacytic infiltrate among the minor salivary glands. Immunoglobulin G (IgG) and IgG4 staining showed 280 IgG4(+) cells per high-power field and a ratio of IgG4(+) to IgG(+) cells of 0.8. The patient subsequently developed bilateral lacrimal gland and parotid gland enlargement associated with an increased serum IgG4 level of 3,031 mg/dL (≤ 135 mg/dL). Left lacrimal gland biopsy confirmed IgG4-related dacryoadenitis. The patient declined corticosteroid treatment for IgG4-related disease (IgG4-RD) and remained stable at 15 months after the first presentation. Spontaneous, partial resolution of the palatal lesion was observed during follow-up. IgG4-RD should be considered in the differential diagnosis of lymphoplasmacytic lesions of the hard palate.

Postoperative haemorrhage in powered endoscopic dacryocystorhinostomy.

BACKGROUND: The rate of postoperative haemorrhage has been reported inconsistently in retrospective studies of endoscopic dacryocystorhinostomy but has not been evaluated prospectively with the powered endoscopic technique. The purpose of this study was to assess the rate of postoperative haemorrhage in patients undergoing powered endoscopic dacryocystorhinostomy. DESIGN: A prospective, single-surgeon, observational case series. PARTICIPANTS: Cases 18 years old or more were included if they presented with radiologically confirmed primary acquired nasolacrimal duct obstruction. Exclusion criteria included evidence of canalicular disease, ectropion or facial palsy, and previous surgery on the lacrimal drainage system. One hundred seventy-four cases fulfilled the criteria for inclusion. The mean age of patients was 62.9 years, 65% were female. METHODS: Powered endoscopic dacryocystorhinostomy. MAIN OUTCOME MEASURE: Postoperative haemorrhage. Significant haemorrhage was defined as that which necessitated packing, cautery, surgical intervention, a blood transfusion or delayed discharge. RESULTS: The rates of total and significant postoperative haemorrhage were 1.7% and 0.6%, respectively. Antithrombotic agents were ceased on a case-by-case basis according to physician recommendation. Aspirin was stopped in 4 of 16 patients taking this agent preoperatively, and warfarin was stopped in one of three patients. CONCLUSION: Significant postoperative haemorrhage following endoscopic dacryocystorhinostomy is rare. Further studies are required to assess whether antithrombotic agents significantly increase the risk of bleeding. The decision to cease agents should be made on a case-by-case basis in consultation with a physician.

Access to the skull base: modular facial disassembly.

Access to the skull base is not new. The different modules of the facial skeleton can be removed to give access to the skull base based on target zones, which were first described by Grime et al in 1991. However, the vertical plane is not considered, and this article adds to the original classification and develops a decision-making algorithm for preferred access to identified lesions of the skull base.

Idiopathic inflammatory orbital myositis presenting with vision loss.

We present a first case of 58-year-old man with vision loss in a biopsy-proven idiopathic inflammatory orbital tendon sparing myositis. Tests for thyroid autoantibodies were negative at the initial presentation and at 10-month follow-up period. The diagnosis was confirmed on histopathological examination and was also supported by avid sarcolemmal staining for MHC-1 and MHC-2.

Epithelial dendritic cells vs. Langerhans cells: Implications for mucosal vaccines.

Next-generation vaccines may be delivered via the skin and mucosa. The stratified squamous epithelium (SSE) represents the outermost layer of the skin (epidermis) and type II mucosa (epithelium). Langerhans cells (LCs) have been considered the sole antigen-presenting cells (APCs) to inhabit the SSE; however, it is now clear that dendritic cells (DCs) are also present. Importantly, there are functional differences in how LCs and DCs take up and process pathogens as well as their ability to activate and polarize T cells, though whether DCs participate in neuroimmune interactions like LCs is yet to be elucidated. A correct definition and functional characterization of APCs in the skin and anogenital tissues are of utmost importance for the design of better vaccines and blocking pathogen transmission. Here, we provide a historical perspective on the evolution of our understanding of the APCs that inhabit the SSE, including a detailed review of the most recent literature.

Initial clinical evaluation of a non-contrast-enhanced MR angiography method in the distal lower extremities.

PURPOSE: To report the initial experience and diagnostic performance applying a novel flow-dependent non-contrast-enhanced MR angiography (NCE-MRA) method, in patients with suspected peripheral vascular disease, in comparison with established contrast-enhanced MRA (CE-MRA). METHODS: The lower legs of 34 patients were imaged at 1.5 T with both NCE-MRA and CE-MRA. The NCE-MRA method consisted of a cardiac-gated balanced-SSFP sequence with controllable flow-suppression preparation. Flow-suppressed and unsuppressed datasets were subtracted to obtain angiograms. Two experienced radiologists assessed both NCE-MRA and CE-MRA images, first independently and then in consensus to resolve significant disagreements. Signal loss, vessel conspicuity, vascular disease, venous contamination, artifacts, and diagnostic confidence were assessed. RESULTS: Using the CE-MRA as the "gold standard," the per-segment sensitivity and specificity for detection of significant disease were 81.7% and 90.9%, respectively. Mean diagnostic confidence (scale 0-4) was 3.4 for NCE-MRA and 3.9 for CE-MRA. Most vessel segments were well visualized but the popliteal arteries often suffered some technique-related signal loss. CONCLUSIONS: The NCE-MRA method was able to visualize most vessel segments with good or excellent confidence, few artifacts, and excellent background suppression, giving moderate agreement with CE-MRA. However, some segments were poorly visualized, probably due to flow profile distortion in these patients.

Tendon sheath fibroma of the medial canthal tendon.

Fibromas of the tendon sheath are slow-growing, benign tumors most commonly found on the hands and wrist. A fibroma of the tendon sheath arising from the medial canthal tendon presented as an enlarging nodule that had been present for 40 years. The fibroma was identified by microscopy and immunohistochemistry, and surgical resection appears to have been curative.