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 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.

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.

Selective Laser Trabeculoplasty: Outcomes of Multiple Repeat Treatments.

PURPOSE: To characterize intraocular pressure (IOP) reduction, effect duration, and side effect profile of repeat selective laser trabeculoplasty (SLT) used as primary stand-alone treatment for open-angle glaucoma (OAG). The secondary aim was to investigate covariates associated with treatment response to SLT. DESIGN: Retrospective chart review. PARTICIPANTS: A total of 52 patients with treatment-naïve OAG who received 3 installments of 3600 SLT as stand-alone glaucoma therapy. When both eyes met the inclusion criteria, only right eye data were used for analysis. METHODS: The study was conducted in a single specialist practice. First, second, and third SLT (SLT1, SLT2, SLT3, respectively) treatments were compared for IOP reduction and effect duration. Eyes were classified as "treatment responders" if they had ≥20% IOP reduction 4 to 8 weeks post-SLT compared with baseline. Effect duration was the interval between SLT and the time point at which the surgeon decided inadequate IOP control necessitated repeat SLT. Individuals were excluded if they underwent intraocular surgery during the study period or received treatment with adjunctive ocular hypotensive medications. MAIN OUTCOME MEASURES: Reduction in IOP post-SLT and effect duration between treatments. RESULTS: Mean age at SLT1 was 58 years; 50% were male, and 92% were phakic. The SLT1 and SLT3 both resulted in mean 27% IOP reduction at 4 to 8 weeks, whereas SLT2 led to 26% IOP reduction. Response rate (≥20% IOP reduction at 4-8 weeks) was 79% for SLT1, 73% for SLT2, and 81% for SLT3, but the difference was not statistically significant. Response to repeat SLT was not significantly associated with previous SLT outcome. Effect duration was 22.2 months, 33.8 months, and 28.9 months after SLT1, SLT2, and SLT3, respectively. Effect duration was significantly longer after SLT2 (P = 0.0006) and SLT3 (P = 0.0444) compared with SLT1. There was no significant association between SLT response and gender, lens status, or OAG subtype. CONCLUSIONS: For primary stand-alone treatment in OAG, initial and repeat SLTs produced comparable percentage IOP reduction, but repeat SLTs had longer effect duration. Intraocular pressure response to SLT was not predictive of the IOP response to subsequent, repeat SLT treatment.

A review of aqueous outflow resistance and its relevance to microinvasive glaucoma surgery.

Primary open-angle glaucoma is the leading cause of irreversible blindness worldwide, and intraocular pressure reduction remains the only proven treatment strategy. Elevated intraocular pressure occurs as the result of impaired aqueous humor outflow. Both a passive model and a dynamic model have been used to explain trabecular outflow resistance. The passive model posits that the trabecular meshwork acts as a static filter that exerts stable and passive resistance to outflow. In contrast, the dynamic model involves a "biomechanical pump." In recent years, the range of surgical management options for glaucoma has dramatically expanded, particularly the class of procedures known as microinvasive glaucoma surgery. These procedures typically target and enhance specific outflow routes. Optimal patient outcomes with microinvasive glaucoma surgery require a clear understanding of aqueous outflow and a surgical approach that is targeted to overcome the site of abnormal resistance in the individual. We review the anatomy and physiology of trabecular and suprachoroidal outflow that is of relevance to microinvasive glaucoma surgery-performing surgeons.

A modified technique for intraluminal stenting of glaucoma drainage devices: The guide-wire technique.

Glaucoma drainage tubes have become increasingly popular in the surgical management of uncontrolled glaucoma. Flow restriction is essential to prevent early postoperative hypotony with non-flow restrictive glaucoma drainage devices. Herein, we describe a new way of using a 3-0 Supramid suture as an intraluminal stent. This technique confers no risk of stent exposure, can be removed ab interno without disturbing the conjunctiva, and aids insertion of the tube into the anterior chamber through a scleral tunnel.

Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.

Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10-6). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups.

Comparing Total Keratometry Measurement on the IOLMaster 700 With Goggin Nomogram Adjusted Anterior Keratometry.

PURPOSE: To compare "total keratometry" measurements with Goggin nomogram adjusted anterior keratometry (GNAK) for toric intraocular lens calculation. METHODS: Routine biometry provided measured total keratometry values from which astigmatism was derived. The Goggin nomogram was applied to anterior keratometry values on the same eyes to provide nomogram-adjusted anterior keratometry values (GNAK) that estimate total corneal astigmatism. The agreement between total keratometry and GNAK was analyzed. RESULTS: Overall, in 46 eyes there was no statistically significant difference between median GNAK and total keratometry power values (P = .746). No statistically significant difference remained in against-the-rule and oblique subgroup analyses. Absolute and signed steep axis of astigmatism was statistically significantly different for GNAK and total keratometry in the overall analysis (P < .001 and = .029, respectively) and for against-the-rule and oblique subgroup analyses. The with-the-rule subgroup showed a statistically significant difference in astigmatic power and no significant signed steep axis difference between GNAK and total keratometry. CONCLUSIONS: Total keratometry appears able to measure total corneal astigmatism to match closely (clinically and statistically) GNAK estimation of that parameter. This indicates that it would be safe and reasonable to use total keratometry data for planning of cataract surgery with toric IOLs. [J Refract Surg. 2018;34(8):521-526.].

Prevalence and type of artefact with spectral domain optical coherence tomography macular ganglion cell imaging in glaucoma surveillance.

PURPOSE: The ganglion cell analysis (GCA) of the CIRRUSTM HD-OCT (Carl Zeiss, Meditec; Dublin, CA) provides measurement of the macular ganglion cell-inner plexiform layer (GCIPL) thickness. This study determined the frequency of scan artefacts and errors in GCIPL imaging in individuals undergoing HD-OCT surveillance for glaucoma. METHOD: A total of 1439 eyes from 721 subjects enrolled in a prospective study assessing predictors of glaucoma progression underwent macular GCIPL imaging with the CIRRUS HD-OCT at recruitment. The prevalence of acquisition errors, segmentation errors, and co-morbid macular pathology was determined. RESULTS: A total of 87 (6.0%) of the 1439 scans had either acquisition errors, segmentation artefacts, or other macular pathology. The most common co-morbid macular pathology was epiretinal membrane in 2.2% of eyes. CONCLUSION: The macular GCIPL scan was artefact free in 94% of eyes. However, epiretinal membrane and high myopia can cause scan artefact and should be considered when interpreting the results.

Antibiotic prophylaxis in cataract surgery in the setting of penicillin allergy: A decision-making algorithm.

Cataract surgery is the most commonly performed surgical procedure in many developed countries. Postoperative endophthalmitis is a rare complication with potentially devastating visual outcomes. Currently, there is no global consensus regarding antibiotic prophylaxis in cataract surgery despite growing evidence of the benefits of prophylactic intracameral cefuroxime at the conclusion of surgery. The decision about which antibiotic regimen to use is further complicated in patients reporting penicillin allergy. Historic statistics suggesting crossreactivity of penicillins and cephalosporins have persisted into modern surgery. It is important for ophthalmologists to consider all available antibiotic options and have an up-to-date knowledge of antibiotic crossreactivity when faced with the dilemma of choosing appropriate antibiotic prophylaxis for patients undergoing cataract surgery with a history of penicillin allergy. Each option carries risks, and the choice may have medicolegal implications in the event of an adverse outcome. We assess the options for antibiotic prophylaxis in cataract surgery in the setting of penicillin allergy and provide an algorithm to assist decision-making for individual patients.