Paul P. Connell

Endogenous endophthalmitis: 10-year experience at a tertiary referral centre

PurposeEndogenous endophthalmitis (EE) is a sight-threatening emergency and the aetiology is often multifactorial. Delayed diagnosis may exacerbate the poor visual prognosis. We describe the management and visual outcomes of EE presenting to a tertiary referral centre.Patients and methodsA prospective consecutive case series of 64 patients presenting with presumed EE from 1997 to 2007 to the Royal Victorian Eye and Ear Hospital were included. All data were collected in a standardized manner. Outcome measures included: visual acuity, microbial profiles, and vitrectomy rate.ResultsIn total, 64 cases of EE were identified over the study period with a mean age of 57.5 years, and 53.5% were male. Presenting acuities ranged from Snellen 6/6 to no perception of light (NPL). Identifiable risk factors were present in 78.1%, with the majority related to intravenous drug abuse. A 64.1% culture positivity rate was recorded. A vitrectomy rate of 57, 56, and 21% was recorded in documented bacterial, fungal, and no growth cases, respectively. Final Snellen acuities ranged from 6/6 to NPL. A total of 5 out of 64 eyes were enucleated, of which 3 identified Klebsiellaspecies. Better visual outcome was documented in fungal cases.ConclusionEE is a serious ocular condition and has a varied aetiology. Visual outcomes are often poor, irrespective of the method of management. Fungal aetiology often confers a better prognosis, and vitrectomy is advocated for bacterial proven cases.

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 Tenons 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.

Risk Factors for Age-Related Maculopathy

Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

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.

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.

Vitreous biomarkers in diabetic retinopathy: a systematic review and meta-analysis.

The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular pathway interactions of these markers found to be consistently associated with DR. Relevant databases [PubMed and ISI web of science] were searched for all published articles investigating molecular biomarkers of the vitreous associated with DR. Based on set exclusion/inclusion criteria available data from studies with human vitreous samples were extracted and used for our meta-analysis. The interactions of significant biomarkers in DR were investigated via STRING and KEGG pathway analysis. Our meta-analysis of DR identifies eleven biomarkers as potential therapeutic candidates alternate to current anti-VEGF therapy. Four of these are deemed viable therapeutic targets for PDR; ET receptors (ET A and ET B), anti-PDGF-BB, blocking TGF-β using cell therapy and PEDF. The identification of supplementary or synergistic therapeutic candidates to anti VEGF in the treatment of DR may aid in the development of future treatment trials.

The optic nerve head in hereditary optic neuropathies

Hereditary optic neuropathies are a prominent cause of blindness in both children and adults. The disorders in this group share many overlapping clinical characteristics, including morphological changes that occur at the optic nerve head. Accurate and prompt clinical diagnosis, supplemented with imaging when indicated, is essential for optimum management of the relevant optic neuropathy and appropriate counseling of the patient on its natural history. Patient history, visual field assessment, optic disc findings and imaging are the cornerstones of a correct diagnosis. This Review highlights the characteristic optic nerve head features that are common to the various hereditary optic neuropathies, and describes the features that enable the conditions to be differentiated.

MACULAR PIGMENT OPTICAL DENSITY IS LOWER IN TYPE 2 DIABETES, COMPARED WITH TYPE 1 DIABETES AND NORMAL CONTROLS.

Purpose: This study was designed to investigate the optical density of macular pigment in Type 1 and Type 2 diabetes subjects relative to normal controls. Methods: One hundred and fifty subjects were recruited to the study and divided into one of the three study groups on the basis of their health status, as follows: Group 1: Healthy controls; Group 2: Type 1 diabetes; Group 3: Type 2 diabetes. Macular Pigment Optical Density, at 0.5° of retinal eccentricity, was measured using customized heterochromatic flicker photometry. Dietary intake of macular carotenoids was quantified using a lutein and zeaxanthin food frequency questionnaire. Diabetes type, duration, medication, smoking habits, glycosylated hemoglobin (HbA1C), and serum lipid levels were recorded, whereas visual acuity, body mass index, and diabetic retinopathy grade were measured for each participant. Results: One-way analysis of variance revealed a statistically significant difference in body mass index, age, high-density lipoprotein cholesterol and HbA1C between the three groups (P < 0.01 for all). Chi-square analysis revealed a statistically significant difference in diabetic retinopathy distribution (P < 0.01). None of these variables exhibited a statistically significant correlation with macular pigment optical density for any study group (P > 0.05 for all). There was no difference in dietary carotenoid intake between groups. Macular pigment optical density was lower among Type 2 diabetes subjects (0.33 ± 0.21) compared with Type 1 diabetes (0.49 ± 0.23) and controls (0.48 ± 0.35). General linear model analysis, including age, body mass index, diabetes duration, diabetic retinopathy status, high-density lipoprotein cholesterol, and HbA1C as covariates, revealed a statistically significant effect of diabetes type on macular pigment optical density (F = 2.62; P = 0.04). Conclusion: Macular pigment optical density was statistically significantly lower in Type 2 diabetes compared with Type 1 diabetes and normal controls. Although body mass index was higher in the Type 2 diabetes group, the lower macular pigment optical density levels observed among Type 2 diabetes seem not to be attributable to differences in dietary carotenoid intake or to the specific presence of diabetes, diabetic control, duration, or diabetic retinopathy.

Hypertensive retinopathy: comparing the Keith-Wagener-Barker to a simplified classification

Purpose: This study assessed the interobserver and intraobserver grading reliability of the Keith–Wagener–Barker (KWB) system to the proposed Mitchell–Wong ‘simplified’ three-grade classification for hypertensive retinopathy. Methods: Digital retinal images of normal and hypertensive human fundii (n = 50 per group) were randomly graded by an optometrist and an ophthalmologist using the two systems. Interobserver agreement was compared to a ‘gold standard’ research grader. Intraobserver agreement was assessed through a repeat grading after 6 months. Cohens kappa coefficients were used to assess the degree of agreement. Results: Both clinicians demonstrated a good level of agreement with the KWB and simplified classification compared with a ‘gold standard’ grader; there was no significant difference in the level of agreement for either of the two classification methods for either observer. The simplified classification was found to be equally as efficacious as the KWB system with respect to interobserver and intraobserver agreement for both practitioners. Conclusion: These findings indicate that the simplified classification of hypertensive retinopathy is both reliable and repeatable. The advantage of the simplified method over the KWB system in correlating retinal microvascular signs to incident cardiovascular risk supports its adoption in clinical practice.

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.