Risk factors, microbial profiles and prognosis of microbial keratitis-associated endophthalmitis in high-risk eyes.

BACKGROUND: Microbial keratitis (MK) is a sight-threatening emergency. Delayed diagnosis and treatment may exacerbate the condition and infection may spread to the posterior segment with resultant endophthalmitis. We describe the presentation, management, visual outcomes and microbial profiles of MK-associated endophthalmitis presenting to a tertiary referral centre. METHODS: Prospective collection of data on all patients presenting with presumed MK-associated endophthalmitis from 1997 to 2007, to the Royal Victorian Eye and Ear Hospital. Outcome measures included: visual acuity, microbial profiles, and management strategy. RESULTS: Thirty-seven cases of MK-associated endophthalmitis were identified over the study period, with a mean age of 73 years and 19 were male. Presenting acuities ranged from Snellen 2/60 to no perception of light (NPL). Thrity-four (91.9%) patients had a prior history of ocular disease. Identifiable non-ocular risk factors were present in 31 (83.8%), including steroid use, dementia, nursing home care or relative systemic immunosuppression. A culture positivity rate of 83.8% was recorded. The most common organisms identified included: Streptococcal species in 12 (32.4%), Pseudomonas aeruginosa in 11 (29.7%), and Staphylococcus aureus in eight (21.6%). Final acuities ranged from 6/36 to NPL. Sixteen (43.2%) eyes were eviscerated/enucleated as primary treatment. Overall, 23 (62.2%) patients required evisceration/enucleation, of which nine (39.1%) were due to Pseudomonas aeruginosa and seven (30.4%) to Streptococcal species (Streptococcal pneumonia). CONCLUSIONS: MK-associated endophthalmitis is a serious ocular condition occurring more frequently in elderly populations, and those with long standing severe pre-existing ocular disease. Visual outcomes are poor, often requiring evisceration/enucleation.

Virtual triaging in an eye emergency department during the COVID-19 pandemic.

AIM: The aim of this audit was to assess the effect of new guidelines on virtual triage referrals to an Irish eye emergency department (EED) during the COVID-19 pandemic. METHODS: A retrospective phone triage referral and clinical note audit was performed to assess outcomes of phone triaging in October. Guidelines for phone triage were formulated with particular regard to what conditions should be seen in EED, treated over the phone or sent straight to outpatients clinic or minor procedures. A prospective phone triage referral and case note audit was then done to assess outcomes after introduction of the guidelines in November. RESULTS: A total of 1700 patients were referred to the eye emergency department, 861 in October and 839 in November. A total of 577 patients were triaged for in-person EED review in November, compared to 692 prior to implementation of guidelines (p < 0.05). The number of patients referred straight to outpatients (p < 0.05) and treated over the phone (p < 0.05) was also significantly increased. Ultimately, the number of conditions unnecessarily triaged to EED, as per the guidelines implemented, was significantly reduced (p < 0.05). CONCLUSION: This audit addressed the need to reduce footfall during the COVID-19 pandemic, identified suitable avenues of referrals for certain conditions, and demonstrated that these guidelines significantly reduced the number of patients presenting to EED with conditions amenable to phone review or clinic follow-up.

Optic disc evaluation in optic neuropathies: the optic disc assessment project.

OBJECTIVE: Optic nerve morphology is affected by genetic and acquired disease. Glaucoma is the most common optic neuropathy; autosomal-dominant optic atrophy (ADOA) and Leber's hereditary optic neuropathy (LHON) are the most prevalent hereditary optic neuropathies. These 3 entities can exhibit similar topographical changes at the optic nerve head. Both ADOA and LHON have been reported to be misdiagnosed as glaucoma. Our aim was to determine whether glaucoma subspecialists and neuro-ophthalmologists can distinguish these diagnoses on optic disc assessment alone. DESIGN: Observational study. PARTICIPANTS: Twenty-three optic nerve experts. METHODS: We randomized and masked 60 high-resolution stereoscopic optic disc photographs (15 ADOA images, 15 LHON, 15 glaucoma, and 15 normal controls). Experts were asked to assess the discs on 12 conventional topographic features and assign a presumptive diagnosis. Intra- and interanalysis was performed using the index of qualitative variation and absolute deviation. MAIN OUTCOME MEASURES: Can glaucoma specialists and neuro-ophthalmologists distinguish among the disease entities by optic nerve head phenotype. RESULTS: The correct diagnosis was identified in 85%, 75%, 27%, and 16% of the normal, glaucoma, ADOA, and LHON disc groups, respectively. The proportion of correct diagnoses within the ADOA and LHON groups was significantly lower than both normal and glaucomatous (P<0.001). Where glaucoma was chosen as the most likely diagnosis, 61% were glaucomatous, 34% were pathologic but nonglaucomatous discs, and 5% were normal. There was greater agreement for individual parameters assessed within the normal disc set when compared with pathologic discs (P<0.05). The only parameter to have a significantly greater agreement within the glaucomatous disc set when compared with ADOA or LHON disc sets was pallor, whereby experts agreed on is absence in the glaucomatous discs but were not in agreement on its presence or its absence in the ADOA and LHON discs (P<0.01). CONCLUSIONS: Optic neuropathies can result in similar topographic changes at the optic disc, particularly in late-stage disease, making it difficult to differentiate ADOA and LHON from glaucoma based on disc assessment alone. Other clinical parameters such as acuity, color vision, history of visual loss, and family history are required to make an accurate diagnosis.

Mitochondrial dysfunction in glaucoma and emerging bioenergetic therapies.

The similarities between glaucoma and mitochondrial optic neuropathies have driven a growing interest in exploring mitochondrial function in glaucoma. The specific loss of retinal ganglion cells is a common feature of mitochondrial diseases - not only the classic mitochondrial optic neuropathies of Leber's Hereditary Optic Neuropathy and Autosomal Dominant Optic Atrophy - but also occurring together with more severe central nervous system involvement in many other syndromic mitochondrial diseases. The retinal ganglion cell, due to peculiar structural and energetic constraints, appears acutely susceptible to mitochondrial dysfunction. Mitochondrial function is also well known to decline with aging in post-mitotic tissues including neurons. Because age is a risk factor for glaucoma this adds another impetus to investigating mitochondria in this common and heterogeneous neurodegenerative disease. Mitochondrial function may be impaired by either nuclear gene or mitochondrial DNA genetic risk factors, by mechanical stress or chronic hypoperfusion consequent to the commonly raised intraocular pressure in glaucomatous eyes, or by toxic xenobiotic or even light-induced oxidative stress. If primary or secondary mitochondrial dysfunction is further established as contributing to glaucoma pathogenesis, emerging therapies aimed at optimizing mitochondrial function represent potentially exciting new clinical treatments that may slow retinal ganglion cell and vision loss in glaucoma.

Prism therapy and visual rehabilitation in homonymous visual field loss.

PURPOSE: Homonymous visual field defects (HVFD) are common and frequently occur after cerebrovascular accidents. They significantly impair visual function and cause disability particularly with regard to visual exploration. The purpose of this study was to assess a novel interventional treatment of monocular prism therapy on visual functioning in patients with HVFD of varied etiology using vision targeted, health-related quality of life (QOL) questionnaires. Our secondary aim was to confirm monocular and binocular visual field expansion pre- and posttreatment. METHODS: Twelve patients with acquired, documented HVFD were eligible to be included. All patients underwent specific vision-targeted, health-related QOL questionnaire and monocular and binocular Goldmann perimetry before commencing prism therapy. Patients were fitted with monocular prisms on the side of the HVFD with the base-in the direction of the field defect creating a peripheral optical exotropia and field expansion. After the treatment period, QOL questionnaires and perimetry were repeated. RESULTS: Twelve patients were included in the treatment group, 10 of whom were included in data analysis. Overall, there was significant improvement within multiple vision-related, QOL functioning parameters, specifically within the domains of general health (p < 0.01), general vision (p < 0.05), distance vision (p < 0.01), peripheral vision (p < 0.05), role difficulties (p < 0.05), dependency (p < 0.05), and social functioning (p < 0.05). Visual field expansion was shown when measured monocularly and binocularly during the study period in comparison with pretreatment baselines. CONCLUSIONS: Patients with HVFD demonstrate decreased QOL. Monocular sector prisms can improve the QOL and expand the visual field in these patients.

Vitreous cavity haemorrhage post-vitrectomy for diabetic eye disease: the effect of perioperative anticoagulation and antiplatelet agents.

BACKGROUND: To evaluate the effect of perioperative anticoagulation and antiplatelet therapy on postoperative vitreous cavity haemorrhage following pars plana vitrectomy for diabetic eye disease. DESIGN: Retrospective chart review. PARTICIPANTS: 139 patients. METHODS: Retrospective collection of demographic, medical, surgical and postoperative data of all patients undergoing vitrectomy for diabetic eye disease at The Royal Victorian Eye and Ear Hospital. MAIN OUTCOME MEASURE: Correlation of the rates of persistent vitreous cavity haemorrhage and anticoagulation or antiplatelet treatment. RESULTS: Sixty-eight of 155 (43.9%) eyes of 139 patients were on anticoagulation or antiplatelet therapy prior to surgery. At the time of surgery, 29 (42.6%) were on therapy. Eight of 29 (27.6%) patients had significant persistent vitreous cavity haemorrhage in the postoperative period, with four (13.8%) requiring secondary surgery. Thirty-nine (57.4%) patients had discontinued therapy prior to surgery. Among these, four (10.3%) had persistent bleeding, of which three (7.7%) required additional surgery. Six of 87 (6.9%) patients not on any anticoagulation/antiplatelet therapy had persistent postoperative vitreous cavity haemorrhage, with none requiring further surgery. Patients on anticoagulation/antiplatelet therapy at the time of surgery were more likely to experience persistent haemorrhage and subsequent reoperation (OR = 4.8, P = 0.0045 and OR = 6.6, P = 0.024, respectively). CONCLUSION: Perioperative continuation of anticoagulation or antiplatelet treatment appears to increase the risk of persistent postoperative vitreous cavity haemorrhage and the necessity for vitreous cavity washout in this diabetic cohort. Appropriate preoperative cessation of treatment appeared to reduce this risk; however, caution must be taken with regard to the systemic risk associated with cessation of therapy.

Glaucomatous optic neuropathy evaluation project: a standardized internet system for assessing skills in optic disc examination.

BACKGROUND: Development of a standardized internet-based system to self-assess skills in optic disc examination for glaucoma risk assessment. DESIGN: Prospective internet-based observational study. PARTICIPANTS: Total of 197 participants (glaucoma subspecialists, general ophthalmologists and trainees) from 22 countries. METHODS: Forty-two optic disc images demonstrating a range of features were selected from 2500 monoscopic disc photographs of normal and glaucomatous eyes. Images were presented to clinicians via website (http://www.gone-project.com). Participants were asked to assess nine topographic features and make a subjective assessment of glaucoma likelihood. MAIN OUTCOME MEASURES: Inter-observer agreement using kappa (κ) or weighted kappa (κ(w) ). RESULTS: There was substantial level of inter-observer agreement between glaucoma subspecialists for assessment of glaucoma likelihood (κ(w) = 0.63). Inter-observer agreement was high for haemorrhage (κ= 0.83) and substantial for disc size, disc shape, cup:disc ratio, peripapillary atrophy and cup shape (κ(w) = 0.59-0.68). Subspecialists had stronger inter-observer agreement for glaucoma likelihood and for most disc characteristics than did trainees: the greatest difference being the assessment for retinal nerve fibre layer loss. Analysis of individual disc answers from ophthalmology trainees showed that discs leading to lower agreement of glaucoma likelihood tend to produce lower agreement for the assessment of cup:disc ratio, cup shape, cup depth and retinal nerve fibre layer. Discs with features of moderate to deep cup or cup:disc ratio between 0.6 and 0.8 also lead to lower agreement in glaucoma likelihood. CONCLUSIONS: This internet-based system is a readily accessible and standardized tool, for clinicians globally, that permits self-assessment and benchmarking of skills in optic disc examination.

Endogenous endophthalmitis associated with intravenous drug abuse: seven-year experience at a tertiary referral center.

PURPOSE: Intravenous drug use (IVDU) is a known risk factor for endogenous endophthalmitis. Endogenous fungal endophthalmitis (EFE) is emerging as a common problem among this community. We describe the management and visual outcomes of acute IVDU-associated EFE. METHODS: A prospective consecutive case series of 19 patients presenting with presumed acute IVDU-associated EFE from 2001 to 2007 to the Royal Victorian Eye and Ear Hospital was included. All data were collected in a standardized manner. Outcome measures included visual acuity, microbial profiles, and vitrectomy rate. RESULTS: Nineteen cases of IVDU-associated EFE were identified. Eight of these (42%) were men, and the mean age was 32.7 years (SD ± 8.0 years). Presenting visual acuity ranged from 6/6 to perception of light, with 58% having a visual acuity of 6/48 or less at presentation. Thirteen (68.4%) were culture positive with all cultures identifying Candida species, and 52.7% underwent vitrectomy. Fifty percent of subjects overall achieved a final visual acuity of 6/18 or better. Men demonstrated improved visual acuity when compared with women (P = 0.04). Age had no effect on final acuity. CONCLUSION: Intravenous drug use is a significant risk factor for developing EFE. Good visual outcomes can be achieved with early treatment, often with intravitreal therapy alone.

Corneal Stiffness and Collagen Cross-Linking Proteins in Glaucoma: Potential for Novel Therapeutic Strategy.

Biomechanical properties of the cornea have recently emerged as clinically useful in risk assessment of diagnosing glaucoma and predicting disease progression. Corneal hysteresis (CH) is a dynamic tool, which measures viscoelasticity of the cornea. It represents the overall deformability of the cornea, and reduces significantly with age. Low CH has also been associated with optic nerve damage and progression of visual field loss in glaucoma. The extracellular matrix (ECM) constituents of the cornea, trabecular meshwork (TM), sclera, and lamina cribrosa (LC) are similar, as they are predominantly made of fibrillar collagen. This suggests that biomechanical changes in the cornea may also reflect optic nerve compliance in glaucomatous optic neuropathy, and in the known increase of TM tissue stiffness in glaucoma. Increased collagen cross-linking contributes to tissue stiffening throughout the body, which is observed in normal aging and occurs at an accelerated rate in systemic conditions such as fibrotic and cardiovascular diseases, cancer, and glaucoma. We reviewed 3 ECM cross-linking proteins that may have a potential role in the disease process of increased tissue stiffness in glaucoma, including lysyl oxidase (LOX)/lysyl oxidase-like 1 (LOXL1), tissue transglutaminase (TG2), and advanced glycation end products. We also report elevated messenger RNA (mRNA) levels of LOX and TG2 in glaucoma LC cells to support our proposed theory that increased levels of cross-linking proteins in glaucoma play a role in LC tissue stiffness. We highlight areas of research that are needed to better understand the role of cross-linking in glaucoma pathogenesis, leading potentially to a novel therapeutic strategy.

Opportunistic detection of glaucomatous optic discs within a diabetic retinopathy screening service.

PURPOSE: To determine the prevalence of glaucoma among patients referred to a glaucoma service with suspicious disc photographs from the diabetic retinopathy (DR) screening program. METHODS: A clinical audit of all patients attending a single-center DR screening program in the Mater Misericordiae University Hospital, Dublin, between July 2010 and October 2011 was conducted with a minimum follow-up of 30 months. The DR screening service uses trained technician graders to assess 2-field color retinal photographs for the features of DR. Recently, the service was enhanced so that optic discs are also assessed for signs of glaucoma. RESULTS: In the 16-month study period, 3,697 diabetic patients were photographed. Following photograph grading, 91 (2.46%) were judged to require referral for assessment at the glaucoma clinic. Of these, 63 (69.23%) presented for assessment. Thirteen patients (20.63%) were diagnosed with glaucoma, comprising 7 cases of low-tension glaucoma and 6 cases of primary open-angle glaucoma. Thirty-six patients (57.14%) were classified as glaucoma suspects and 14 patients (22.22%) were discharged back to the DR screening program following normal ocular examination. Only 6 (9.52%) of the 63 patients examined had an intraocular pressure greater than 21 mm Hg. CONCLUSIONS: The assessment of DR screening photographs for signs of glaucomatous optic nerve damage should be considered as part of a strategy to improve glaucoma case detection and to reduce the burden of this disease on society.

Upper and lower limb muscle power relationships in mobility-limited older adults.

BACKGROUND: Lower limb muscle power impairments are modifiable factors underlying mobility limitations in older adults. This study examined relationships between upper and lower limb muscle power and their role in predicting mobility performance among community-dwelling older adults. METHODS: A cross-sectional analysis was conducted. Participants included 37 mobility-limited adults (24 women, 13 men), aged 65 to 93 years. Measures included upper (elbow extension) and lower limb (double leg press) one repetition maximum (1RM), and muscle power at both 40% and 70% one repetition maximum. Physical performance measures included stair climb time, the Short Physical Performance Battery, and 4-meter walk time. Factors commonly mediating the relationship between impairments and physical performance were analyzed as covariates. RESULTS: Participants had a mean age of 76 years, had five chronic medical conditions, and manifested moderate mobility limitations. Although the associations between the upper and lower limbs were strong (p <.001), the magnitude of association was greater for power (r =.88-.89) as compared to strength (r =.69). Multivariate regression analyses revealed consistently strong relationships between limb muscle power and mobility performance measures. Substituting upper for lower limb power within these models did not materially weaken the relationships. CONCLUSION: Muscle power appears to be a more generalized attribute between the upper and lower limbs than is muscle strength, suggesting that mechanisms underlying velocity of movement, as opposed to force production, may be important factors underlying muscle power in elderly persons. Additionally, upper limb muscle power measures may serve as a useful surrogate measure of limb power having implications for clinicians and researchers.

Oxandrolone Augmentation of Resistance Training in Older Women: A Randomized Trial.

INTRODUCTION: Sarcopenia is disproportionately present in older women with disability, and optimum treatment is not clear. We conducted a double-blind, randomized, placebo-controlled trial to determine whether oxandrolone administration in elderly women improves body composition or physical function beyond that which occurs in response to progressive resistance training (PRT). METHODS: Twenty-nine sedentary women (age 74.9 ± 6.8 yr; 5.9 ± 2.8 medications per day) were randomized to receive high-intensity PRT (three times a week for 12 wk) combined with either oxandrolone (10 mg·d(-1)) or an identical placebo. Peak strength was assessed for leg press, chest press, triceps, knee extension, and knee flexion. Power was assessed for leg press and chest press. Physical function measures included static and dynamic balance, chair rise, stair climb, gait speed, and 6-min walk test. Body composition was assessed using dual energy x-ray absorptiometry. RESULTS: Oxandrolone treatment augmented increases in lean tissue for the whole body (2.6 kg; 95% confidence interval (CI), 1.0-4.2 kg; P = 0.003), arms (0.3 kg; 95% CI, 0.1-0.5 kg; P = 0.001), legs (0.8 kg; 95% CI, 0.1-1.4 kg; P = 0.018), and trunk (1.4 kg; 95% CI, 0.4-2.3 kg; P = 0.004). Oxandrolone also augmented loss of fat tissue of the whole body (-1 kg; 95% CI, -1.6 to -0.4; P = 0.002), arms (-0.2 kg; 95% CI, -0.5 to -0.02 kg; P = 0.032), legs (-0.4 kg; 95% CI, -0.6 to -0.1; P = 0.009), and tended to reduce trunk fat (-0.4 kg; 95% CI, -0.9 to 0.04; P = 0.07). Improvements in muscle strength and power, chair stand, and dynamic balance were all significant over time (P < 0.05) but not different between groups (P > 0.05). CONCLUSIONS: Oxandrolone improves body composition adaptations to PRT in older women over 12 wk without augmenting muscle function or functional performance beyond that of PRT alone.

Higher dietary variety is associated with better nutritional status in frail elderly people.

OBJECTIVE: A narrow range of food choices may lead to dietary inadequacies, a particular concern in elderly people. We hypothesized that consumption of a more diverse diet would predict better nutritional status in frail elderly persons. SUBJECTS: Subjects included 98 frail nursing home residents (36 men, 62 women), mean age 87.1+/-5.5 (72 to 98) years. METHODS: 3-day dietary variety scores ranging from 23 to 48 and fruit and vegetable variety scores ranging from 5 to 20 were calculated from weighed 3-day food records as the number of different food or fruit and vegetable choices consumed. A higher score indicates a more varied diet. Nutritional status was assessed by weight, height, body mass index (BMI), skinfold thickness, circumference measures, calculated mean arm muscle area, total body water, computerized tomography of the thigh, and total body potassium, as well as nutritional analysis, biochemical measures, and subject medical history. STATISTICAL METHODS: Univariate regression analyses were performed to investigate the relationship between clinical and nutrition variables. Multiple linear regressions were used to develop models relating dietary variety scores to possible etiologic factors as well as indicators of nutritional status. Models were controlled for age, BMI, and energy intake when appropriate. RESULTS: Mean dietary variety score was 35.2+/-4.5, and mean fruit and vegetable variety score was 11.3+/-3.0. Higher dietary variety score was associated with higher energy intake (beta = 20.5, P < .001) and both high dietary variety score and fruit and vegetable variety score were positively associated with intake for many nutrients (P < or = .05). High dietary variety score was related to high fruit and vegetable variety score and total intake of fruits and vegetables. In men, higher dietary variety score and fruit and vegetable variety score were associated with higher high-density lipoprotein (beta = 1.02), lower very-low-density lipoprotein (beta = -3.58) and triglycerol (beta = -3.51), and higher blood folate (beta = 4.72) concentrations in women (P < or = .05). In women, high dietary variety score was associated with higher BMI (beta = 0.34, P < .001) and higher total body potassium (beta = 1.30, P = .02); high fruit and vegetable variety score was associated with higher BMI (beta = 0.41), mid-arm circumference (beta = 0.34), and mid-arm muscle area (beta = 2.94) (P < or = .03). Dietary variety score was higher (mean 37.6+/-5.38 vs 34.6+/-4.14) in those who received assistance with feeding (beta = 2 .67, P = .01). History of cancer (beta = -2.04) and gastrointenstinal cancer (beta = -3.54) were associated with low dietary variety score (P < or = .05). CONCLUSIONS: The results of this study suggest that a highly varied diet in elderly nursing home residents is associated with better nutritional status as assessed by nutrient intake, biochemical measures, and body composition measures. Dietary variety score is a straightforward tool for screening and identifying people at nutritional risk, as well as a mechanism for monitoring response to nutritional, medical, and environmental interventions. Preventive measures to improve dietary variety, as measured by the dietary variety score, should be evaluated and introduced before nutrition and health complications arise.

Glaucomatous optic neuropathy evaluation (GONE) project: the effect of monoscopic versus stereoscopic viewing conditions on optic nerve evaluation.

PURPOSE: To determine whether monoscopic vs stereoscopic viewing impacts evaluation of optic disc photographs for glaucoma diagnosis in an expert population. DESIGN: Prospective observational study. METHODS: Twenty pairs of high-quality monoscopic and stereoscopic photographs of similar size and magnification (ie, 40 images), were selected to demonstrate a range of optic disc features from a total of 197 eyes of 197 patients with glaucoma and normal subjects recruited from a tertiary clinic. These were presented in randomized order via an interactive platform (http://stereo.gone-project.com/). Participants assessed 9 topographic features and estimated glaucoma likelihood for each photograph. Main outcome measures were intra- and inter-observer agreement. RESULTS: There was good intra-observer agreement between monoscopic and stereoscopic assessments of glaucoma likelihood (κw = 0.56). There was also good to substantial agreement for peripapillary atrophy (κw = 0.65), cup shape (κw = 0.65), retinal nerve fiber layer loss (κw = 0.69), vertical cup-to-disc ratio (κw = 0.58), and disc shape (κw = 0.57). However, intra-observer agreement was only fair to moderate for disc tilt, cup depth, and disc size (κw = 0.46-0.49). Inter-observer agreement for glaucoma likelihood in monoscopic photographs (κw = 0.61, 95% confidence interval [CI] = 0.55-0.67) was substantial and not lower than in stereoscopic photographs (κw = 0.59, CI = 0.54-0.65). Monoscopic photographs did not lead to lower levels of inter-observer agreement compared to stereoscopic photographs in the assessment of any optic disc characteristics, for example disc size (mono κw = 0.65, stereo κw = 0.52) and cup-to-disc ratio (mono κw = 0.72, stereo κw = 0.62). CONCLUSIONS: For expert observers in the evaluation of optic disc photographs for glaucoma likelihood, monoscopic optic disc photographs did not appear to represent a significant disadvantage compared to stereoscopic photographs.

Glaucomatous optic neuropathy evaluation project: factors associated with underestimation of glaucoma likelihood.

IMPORTANCE: Glaucoma is a significant health problem for which diagnosis remains suboptimal. Optic disc evaluation, which is fundamental to the diagnosis, is a difficult skill to acquire. OBJECTIVES: To determine the optic disc characteristics that most influence decision making in the assessment of glaucoma likelihood and to ascertain the optic disc features associated with overestimation and underestimation of glaucoma likelihood. DESIGN, SETTING, AND PARTICIPANTS: This prospective, observational, Internet-based study with multinational participation included 197 ophthalmic clinicians (37 glaucoma subspecialists, 51 comprehensive ophthalmologists, and 109 ophthalmology trainees) from 22 countries who self-registered for the Glaucomatous Optic Neuropathy Evaluation (GONE) Project from December 1, 2008 through June 30, 2010. INTERVENTIONS: A series of 42 monoscopic optic disc photographs of healthy and glaucomatous eyes were presented to clinicians using the GONE Project Program. Participants were asked to assess each disc according to 9 conventional topographic features and assign a presumptive grade for glaucoma likelihood. MAIN OUTCOMES AND MEASURES: Agreement (κ and weighted κ) among participants for disc signs and glaucoma likelihood and contributions of disc-related factors to overestimation and underestimation of glaucoma likelihood. RESULTS: Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in a mean (SD) of 22.1% (1.6%) and 23.8% (1.8%) of discs, respectively. Underestimation of vertical cup-disc ratio and failure to identify retinal nerve fiber layer loss, disc hemorrhage, or rim loss were most likely to lead to underestimation of glaucoma. When all 4 features were inaccurately assessed, underestimation of glaucoma likelihood increased to 43.0%. Ophthalmology trainees and comprehensive ophthalmologists overestimated glaucoma likelihood in a mean (SD) of 13.0% (1.2%) and 8.9% (1.3%) of discs, respectively. Overestimation of glaucoma likelihood was associated with overestimation of retinal nerve fiber layer loss, rim loss, vertical cup-disc ratio, disc hemorrhage, and incorrect assessment of disc tilt and was more likely in large discs. CONCLUSIONS AND RELEVANCE: Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in approximately 1 in 5 disc photographs and were twice as likely to underestimate as overestimate glaucoma likelihood. Underestimating the vertical cup-disc ratio and cup shape and missing retinal nerve fiber layer defects and disc hemorrhage were the key errors that led to underestimation. When all 4 parameters were incorrectly assessed, underestimation increased to almost 1 in 2.

Impaired complex-I-linked respiration and ATP synthesis in primary open-angle glaucoma patient lymphoblasts.

PURPOSE: Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes of POAG patients, the authors sought to characterize mitochondrial function in a separate cohort of POAG. METHODS: Using similar methodology to that previous applied to Leber's hereditary optic neuropathy (LHON) patients, maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well as cell growth rates in glucose and galactose media, were assessed in transformed lymphocytes from POAG patients (n = 15) and a group of age- and sex-matched controls (n = 15). RESULTS: POAG lymphoblasts had significantly lower rates of complex-I-driven ATP synthesis, with preserved complex-II-driven ATP synthesis. Complex-I driven maximal respiration was also significantly decreased in patient cells. Growth in galactose media, where cells are forced to rely on mitochondrial ATP production, revealed no significant differences between the control and POAG cohort. CONCLUSIONS: POAG lymphoblasts in the study cohort exhibited a defect in complex-I of the oxidative phosphorylation pathway, leading to decreased rates of respiration and ATP production. Studies in LHON and other diseases have established that lymphocyte oxidative phosphorylation measurement is a reliable indicator of systemic dysfunction of this pathway. While these defects did not impact lymphoblast growth when the cells were forced to rely on oxidative ATP supply, the authors suggest that in the presence of a multitude of cellular stressors as seen in the early stages of POAG, these defects may lead to a bioenergetic crisis in retinal ganglion cells and an increased susceptibility to cell death.

Mitochondrial disorders and the eye.

The clinical significance of disturbed mitochondrial function in the eye has emerged since mitochondrial DNA (mtDNA) mutation was described in Leber's hereditary optic neuropathy. The spectrum of mitochondrial dysfunction has become apparent through increased understanding of the contribution of nuclear and somatic mtDNA mutations to mitochondrial dynamics and function. Common ophthalmic manifestations of mitochondrial dysfunction include optic atrophy, pigmentary retinopathy, and ophthalmoplegia. The majority of patients with ocular manifestations of mitochondrial disease also have variable central and peripheral nervous system involvement. Mitochondrial dysfunction has recently been associated with age-related retinal disease including macular degeneration and glaucoma. Therefore, therapeutic targets directed at promoting mitochondrial biogenesis and function offer a potential to both preserve retinal function and attenuate neurodegenerative processes.

Gaze behavior among experts and trainees during optic disc examination: does how we look affect what we see?

PURPOSE: The authors compared the visual gaze behaviors of glaucoma subspecialists with those of ophthalmology trainees during optic disc and retinal nerve fiber layer (RNFL) examination. METHODS: Seven glaucoma subspecialists and 23 ophthalmology trainees participated in the project. Participants were shown eight glaucomatous optic disc images with varied morphology. Eye movements during examination of the optic disc photographs were tracked. For each disc image, graders were asked to assign a presumptive diagnosis for probability of glaucoma. There was no time restriction. RESULTS: Overall, trainees spent more time looking at disc images than glaucoma subspecialists (21.3 [13.9-37.7] vs. 16.6 [12.7-19.7]) seconds; median [interquartile range (IQR)], respectively; P < 0.01) and had no systematic patterns of gaze behavior, and gaze behavior was unaltered by disc morphology or topographic cues of pathology. Experienced viewers demonstrated more systematic and ordered gaze behavior patterns and spent longer times observing areas with the greatest likelihood of pathology (superior and inferior poles of the optic nerve head and adjacent RNFL) compared with the trainees. For discs with focal pathology, the proportion of total time spent examining definite areas of pathology was 28.9% (22.4%-33.6%) for glaucoma subspecialists and 13.5% (12.2%-19.2%) for trainees (median [IQR]; P < 0.05). Furthermore, experts adapted their viewing habits according to disc morphology. CONCLUSIONS: Glaucoma subspecialists adopt systematic gaze behavior when examining the optic nerve and RNFL, whereas trainees do not. It remains to be elucidated whether incorporating systematic viewing behavior of the optic disc and RNFL into teaching programs for trainees may expedite their acquisition of accurate and efficient glaucoma diagnosis skills.

The optic nerve head in acquired optic neuropathies.

Acquired optic neuropathies are a common cause of blindness in adults, and are associated with characteristic morphological changes at the optic nerve head. Accurate and prompt clinical diagnosis, supplemented with imaging where appropriate, is essential to optimize management of the optic neuropathy and to counsel the patient appropriately on its natural history. History taking, optic disc findings, visual field assessment and imaging of the nerve head and surrounding retinal nerve fiber layer are all paramount to achieving the correct diagnosis. This Review highlights the optic nerve head features that are common to the acquired optic neuropathies, and describes the features that can be used to differentiate these various conditions.

Antifibrotic activity of bevacizumab on human Tenon's fibroblasts in vitro.

PURPOSE: To evaluate the effect of the anti-VEGF-A monoclonal antibody bevacizumab on primary human Tenon's capsule fibroblasts (HTFs) in an in vitro model of wound healing. METHODS: Fibroblasts were cultured in RPMI media, and bevacizumab was administered at a concentration ranging from 0.25 to 12.5 mg/mL. Fibroblast viability and cell death were assessed using the MTT colorimetric assay, lactate dehydrogenase assay, BrdU assay, and live/dead assay. Fibroblast contractility was assessed in floating collagen gels. Morphologic changes were assessed by transmission electron microscopy. Antifibrosis activities were compared with 5-fluorouracil. RESULTS: Bevacizumab induced a significant dose-related reduction of HTF cell number at 12.5 mg/mL at 72 hours (P < 0.05). Under serum-free conditions, bevacizumab induced significant fibroblast cell death at concentrations greater than 7.5 mg/mL (P < 0.05). Bevacizumab caused a moderate inhibition of fibroblast gel contraction from baseline (P < 0.05). Scanning electron microscopy revealed marked vacuolization in bevacizumab-treated fibroblasts. CONCLUSIONS: Bevacizumab disrupted fibroblast proliferation, inhibited collagen gel contraction ability, and induced fibroblast cell death at concentrations greater than 7.5 mg/mL in serum-free conditions. These results demonstrated that bevacizumab inhibited a number of fibrosis activities in culture. These activities may underpin the antifibrosis effect proposed in vivo.