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Infectious diseases are a significant health burden for developing countries, particularly with the rise of multidrug resistance. There is an urgent need to elucidate the factors underlying the persistence of pathogens such as Mycobacterium tuberculosis, Plasmodium falciparum and Trypanosoma brucei. In contrast to host cells, these pathogens traverse multiple and varied redox environments during their infectious cycles, including exposure to high levels of host-derived reactive oxygen species. Pathogen antioxidant defenses such as the peroxiredoxin and thioredoxin systems play critical roles in the redox stress tolerance of these cells. However, many of the kinetic rate constants obtained for the pathogen peroxiredoxins are broadly similar to their mammalian homologs and therefore, their contributions to the redox tolerances within these cells are enigmatic. Using graph theoretical analysis, we show that compared to a canonical Escherichia coli redoxin network, pathogen redoxin networks contain unique network connections (motifs) between their thioredoxins and peroxiredoxins. Analysis of these motifs reveals that they increase the hydroperoxide reduction capacity of these networks and, in response to an oxidative insult, can distribute fluxes into specific thioredoxin-dependent pathways. Our results emphasize that the high oxidative stress tolerance of these pathogens depends on both the kinetic parameters for hydroperoxide reduction and the connectivity within their thioredoxin/peroxiredoxin systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Peroxiredoxins play central roles in the detoxification of reactive oxygen species and have been modelled across multiple organisms using a variety of kinetic methods. However, the peroxiredoxin dimer-to-decamer transition has been underappreciated in these studies despite the 100-fold difference in activity between these forms. This is due to the lack of available kinetics and a theoretical framework for modelling this process. Using published isothermal titration calorimetry data, we obtained association and dissociation rate constants of 0.050 µM -4 ·s -1 and 0.055 s -1 , respectively, for the dimer-decamer transition of human PRDX1. We developed an approach that greatly reduces the number of reactions and species needed to model the peroxiredoxin decamer oxidation cycle. Using these data, we simulated horse radish peroxidase competition and NADPH-oxidation linked assays and found that the dimer-decamer transition had an inhibition-like effect on peroxidase activity. Further, we incorporated this dimer-decamer topology and kinetics into a published and validated in vivo model of PRDX2 in the erythrocyte and found that it almost perfectly reconciled experimental and simulated responses of PRDX2 oxidation state to hydrogen peroxide insult. By accounting for the dimer-decamer transition of peroxiredoxins, we were able to resolve several discrepancies between experimental data and available kinetic models.

Background: An increasing proportion of people have a body mass index (BMI) classified as overweight or obese and published studies disagree whether this will be beneficial or detrimental to health. We applied and evaluated two intergenerational instrumental variable methods to estimate the average causal effect of BMI on mortality in a cohort with many deaths: the parents of UK Biobank participants., Methods: In Cox regression models, parental BMI was instrumented by offspring BMI using an 'offspring as instrument' (OAI) estimation and by offspring BMI-related genetic variants in a 'proxy-genotype Mendelian randomization' (PGMR) estimation., Results: Complete-case analyses were performed in parents of 233 361 UK Biobank participants with full phenotypic, genotypic and covariate data. The PGMR method suggested that higher BMI increased mortality with hazard ratios per kg/m2 of 1.02 (95% CI: 1.01, 1.04) for mothers and 1.04 (95% CI: 1.02, 1.05) for fathers. The OAI method gave considerably higher estimates, which varied according to the parent-offspring pairing between 1.08 (95% CI: 1.06, 1.10; mother-son) and 1.23 (95% CI: 1.16, 1.29; father-daughter)., Conclusion: Both methods supported a causal role of higher BMI increasing mortality, although caution is required regarding the immediate causal interpretation of these exact values. Evidence of instrument invalidity from measured covariates was limited for the OAI method and minimal for the PGMR method. The methods are complementary for interrogating the average putative causal effects because the biases are expected to differ between them., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Large numbers of women take prescription and over-the-counter medications during pregnancy. However, there is very little definitive evidence about the potential effects of these drugs on the mothers and offspring. We will investigate the risks and benefits of continuing prescriptive drug use for chronic pre-existing maternal conditions such as diabetes, hypertension and thyroid related conditions throughout pregnancy. If left untreated, these conditions are established risk factors for adverse neonatal and maternal outcomes. However, some treatments for these conditions are associated with adverse neonatal outcomes. Our primary aims are twofold. Firstly, we aim to estimate the beneficial effect on the mother of continuing treatment during pregnancy. Second, we aim to determine whether there is an associated detrimental impact on the neonate of continuation of maternal treatment during pregnancy. To establish this evidence, we will investigate the relationship between maternal drug prescriptions and adverse and beneficial offspring outcomes to provide evidence to guide clinical decisions. We will conduct a hypothesis testing observational intergenerational cohort study using data from the UK Clinical Practice Research Datalink (CPRD). We will apply four statistical methods: multivariable adjusted regression, propensity score regression, instrumental variables analysis and negative control analysis. These methods should account for potential confounding when estimating the association between the drug exposure and maternal or neonatal outcome. In this protocol we describe the aims, motivation, study design, cohort and statistical analyses of our study to aid reproducibility and transparency within research., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Barry CJ et al.)

Background/aims: To explore the relationship between focal lamina defect (LD) size and optic disc haemorrhages (DH) in glaucomatous eyes., Methods: Radial B-scan images at 15° intervals obtained using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (OCT) were performed on a group of subjects previously assessed for DH every 3 months over a period of 5 years. EDI-OCT scans were assessed for the presence of focal lamina cribrosa defects by a single observer., Results: 119 eyes from 62 subjects (44 females, 18 males) were analysed. 44 eyes (37%) were noted to have at least 1 LD, and of those, eight eyes had more than one defect. 68 eyes (57%) were observed to have at least one DH occur over the course of monitoring. 48 eyes (40%) had recurrent DH, with a mean of 5.17 haemorrhages over the 5-year period. Type 1 focal LD (p=0.0000, OR 7.17), glaucoma progression (p=0.0024, OR 0.32) and ArtDiff (p=0.0466, OR 1.04) were significantly associated as predictors of DH. No correlation between the size of the LD and DH occurrence (p=0.6449, Spearman rank correlation) was found., Conclusion: Focal lamina cribrosa hole-type defects were significantly associated with an increase in DH occurrence over the preceding 5 years. The lack of association between defect size and DH suggests that DH and lamina defects may have separate links to the glaucomatous process., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To delineate morphometric and quantitative features of the capillary image derived from high-resolution fundus fluorescein angiography (FFA) and consequently determine the diagnostic value of FFA for studying the retinal capillary circulation., Methods: Retinal capillary images obtained from healthy young subjects using high-resolution FFA were compared with confocal scanning laser microscopic capillary images derived from the retinas of age-matched human donors. Confocal microscopic images were acquired from retinal flatmount tissue after central retinal artery cannulation, perfusion fixation, and antibody labeling. Capillary images from equivalent retinal regions were morphologically and quantitatively analyzed in both groups., Results: Ten human subjects (mean age, 27.4 years) were used for FFA studies, and five cadaveric eyes (mean donor age, 26.5 years) were used for histologic studies. In histologic specimens the density of the superficial capillary network was significantly greater than that of the deep capillary network. Despite use of a healthy young population, only 30% of high-resolution FFA studies provided clear capillary images. The configuration of the capillary network in FFA images was comparable to the superficial capillary network in confocal microscope images; however, the density of the capillary network in FFA images was consistently lower than that of histologic images., Conclusions: FFA provides incomplete morphologic information about the superficial capillary network and even less information about the deep capillary network. Caution should, therefore, be exercised when using FFA data to extrapolate information about microvascular histopathologic processes. The usefulness of newer technology for studying retinal capillary detail should be investigated.

Corneal neovascularization can be a difficult problem to treat. The authors describe a patient with lipid keratopathy secondary to corneal neovascularization treated with photodynamic therapy. Six months following treatment the neovascularization has not returned and the lipid keratopathy has not increased in size. No significant side effects from the treatment occurred. Photodynamic therapy with Verteporfin was a useful treatment modality in this case of corneal neovascularization with associated lipid keratopathy., (Copyright 2010, SLACK Incorporated.)

Aim: Retinal vein ophthalmodynamometric force (ODF) is predictive of future optic disc excavation in glaucoma, but it is not known if variation in ODF affects prognosis. We aimed to assess whether a change in ODF provides additional prognostic information., Methods: 135 eyes of 75 patients with glaucoma or being glaucoma suspects had intraocular pressure (IOP), visual fields, stereo optic disc photography and ODF measured on an initial visit and a subsequent visit at mean 82 (SD 7.3) months later. Corneal thickness and blood pressure were recorded on the latter visit. When venous pulsation was spontaneous, the ODF was recorded as 0 g. Change in ODF was calculated. Flicker stereochronoscopy was used to determine the occurrence of optic disc excavation, which was modelled against the measured variables using multiple mixed effects logistic regression., Results: Change in ODF (p = 0.046) was associated with increased excavation. Average IOP (p = 0.66) and other variables were not associated. Odds ratio for increased optic disc excavation of 1.045 per gram ODF change (95% CI 1.001 to 1.090) was calculated., Conclusion: Change in retinal vein ODF may provide additional information to assist with glaucoma prognostication and implies a significant relationship between venous change and glaucoma patho-physiology.

Ophthalmic imaging has changed dramatically since the 1960s with increasingly complex technologies now available. Arguably, the greatest changes have been the development of the digital camera and the speed, processing power and storage of electronic data. Already, ophthalmic practices in many major institutions overseas have paperless medium storage and electronically generated reporting from all equipment that use a computer interface. It is hard to remember the widespread use of photographic film with its attendant costs, or even to remember the days before optical coherence tomography (OCT). These latest technical improvements in ophthalmic imaging are now standard in large Australian institutions and becoming more widespread in smaller private practices. The technicians that operate and maintain this ever-increasing plethora of gadgetry have seen their work practices change from the darkroom to the complexities of data-based imaging and storage. It is a fitting time to examine the contemporary state of ophthalmic imaging and what lies on the horizon as we move towards 2020.

The synthesis of a novel gut selective MTP inhibitor, 5-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), and its in vitro and in vivo profile are described. Dirlotapide (3) demonstrated excellent potency against MTP enzyme in HepG2 cells and canine hepatocytes. This novel MTP inhibitor also showed excellent efficacy when tested in a canine food intake model.

Background: Retinal vein pulsation is often absent in glaucoma, but can be induced by applying a graded ophthalmodynamometric force (ODF) to the eye, which is elevated in glaucoma., Aim: To assess whether ODF has a predictive value in determining glaucoma progression., Methods: 75 patients with glaucoma and suspected glaucoma were examined prospectively in 1996, and then re-examined at a mean of 82 months later. All subjects had intraocular pressure, visual fields, stereo optic disc photography and ODF measured on their initial visit. When venous pulsation was spontaneous, the ODF was said to be 0 g. At re-examination, central corneal thickness and blood pressure were also measured. Initial and subsequent optic disc photographs were compared and graded into those that had increased excavation and those that had remained stable. The relationship between increased excavation (recorded as a binary response) and the measured variables was modelled using a multiple mixed effects logistic regression., Results: ODF at the initial visit was strongly predictive of increased excavation (p = 0.004, odds ratio 1.16/g, range 0-60 g), with greater predictive value in women than in men (p = 0.004). Visual field mean deviation was predictive of increased excavation (p = 0.044), as was optic nerve haemorrhage in association with older age (p = 0.038). Central corneal thickness was not significantly predictive of increased excavation (p = 0.074) after having adjusted for other variables., Conclusion: ODF measurement seems to be strongly predictive of the patient's risk for increased optic disc excavation. This suggests that ODF measurement may have predictive value in assessing the likelihood of glaucoma progression.

Time to failure and electromyogram activity were measured during two types of sustained submaximal contractions with the elbow flexors that required each subject to exert the same net muscle torque with the forearm in two different postures. Twenty men performed the tasks, either by maintaining a constant force while pushing against a force transducer (force task), or by supporting an equivalent load while maintaining a constant elbow angle (position task). The time to failure for the position task with the elbow flexed at 1.57 rad and the forearm horizontal was less than that for the force task (5.2 +/- 2.6 and 8.8 +/- 3.6 min, P = 0.003), whereas it was similar when the forearm was vertical (7.9 +/- 4.1 and 7.8 +/- 4.5 min, P = 0.995). The activity of the rotator cuff muscles was greater during the position tasks (25.1 +/- 10.1% maximal voluntary contraction) compared with the force tasks (15.2 +/- 5.4% maximal voluntary contraction, P < 0.001) in both forearm postures. However, the rates of increase in electromyogram of the accessory muscles and mean arterial pressure were greater for the position task only when the forearm was horizontal (P < 0.05), whereas it was similar for the elbow flexors. These findings indicate that forearm posture influences the difference in the time to failure for the two fatiguing contractions. When there was a difference between the two tasks, the task with the briefer time to failure involved greater rates of increase in accessory muscle activity and mean arterial pressure.

We have successfully identified a number of novel MTP inhibitors with single digit nanomolar potency. Analogues 10aq and 10dq demonstrated in vivo efficacy in a murine gut retention assay.

Western Australia has a large landmass and low population density. Dating back to the 1970s and even today, specialist medical services are often lacking or non-existent outside of Perth, the capital city. Diabetes has always been a major health problem, particularly in the Australian Aboriginal community. In conjunction with the Lions Save Sight Foundation and Diabetes Foundation of Western Australia a diabetic screening programme was initiated in 1978 for rural and remote diabetics. The programme aimed to screen for diabetic retinopathy, educate diabetics, medical and paramedical personnel and to arrange treatment for sight threatening eye disease. Eye screening continues to date although the role of the Lions Eye Institute has changed from programme initiator to reading centre and teaching unit, and continues to evolve with changing technologies.

Aim: To generate a mouse model for slow progressive retinal neovascularisation through vascular endothelial growth factor (VEGF) upregulation., Methods: Transgenic mice were generated via microinjection of a DNA construct containing the human VEGF165 (hVEGF) gene driven by a truncated mouse rhodopsin promoter. Mouse eyes were characterised clinically and histologically and ocular hVEGF levels assayed by ELISA., Results: One transgenic line expressing low hVEGF levels showed mild clinical changes such as focal fluorescein leakage, microaneurysms, venous tortuosity, capillary non-perfusion and minor neovascularisation, which remained stable up to 3 months postnatal. Histologically, there were some disturbance and thinning of inner and outer nuclear layers, with occasional focal areas of neovascularisation. By contrast, three other lines expressing high hVEGF levels presented with concomitantly severe phenotypes. In addition to the above, clinical features included extensive neovascularisation, haemorrhage, and retinal detachment; histologically, focal to extensive areas of neovascularisation associated with retinal folds, cell loss in the inner and outer nuclear layers, and partial retinal detachment were common., Conclusions: The authors generated four hVEGF overexpressing transgenic mouse lines with phenotypes ranging from mild to severe neovascularisation. These models are a valuable research tool to study excess VEGF related molecular and cellular changes and provide additional opportunities to test anti-angiogenic therapies.

Purpose: To investigate in vitro the effects of selected drugs on the spoliation of poly(2-hydroxyethyl methacrylate) (PHEMA), a synthetic acrylic hydrogel currently used for the manufacture of a keratoprosthesis, AlphaCor. The experiments were carried out both in the presence of simulated aqueous humor (SAH) and in its absence., Methods: Disks of PHEMA were incubated and shaken with 9 commonly prescribed drugs at 37 degrees C in sterile conditions for 1 week. Samples were incubated either in SAH only (controls), in each drug preparation, or in each drug for 1 week followed by 1 week in SAH. The drugs selected for this study were steroids (prednisolone, dexamethasone, fluorometholone, medroxyprogesterone), antiglaucoma drugs (timolol maleate and pilocarpine), and antibiotics (chloramphenicol, cephazolin, and ciprofloxacin), as commercially available formulations. Following incubation, the PHEMA specimens were examined visually and then histologically, after staining with alizarin red for the presence of calcium in the spoliating sediments/deposits., Results: Although only 5 of the drug formulations (dexamethasone as Maxidex, fluorometholone as FML, pilocarpine as Isopto Carpine, chloramphenicol as Chlorsig, and medroxyprogesterone as Depo-Ralovera) induced spoliation of the hydrogel in the absence of SAH, all drugs induced spoliation after postincubation in SAH, and calcium was detected in the majority of samples. The deposits on the hydrogel specimens incubated first in cephazolin (as Cefazolin-BC), pilocarpine (as Isopto Carpine), and chloramphenicol (as Chlorsig) and then in SAH did not contain calcium, despite its presence in SAH., Conclusions: The study appears to confirm our earlier clinical observations that topical medication may play a role in the spoliation of the hydrogel ophthalmic devices. Presence of calcium in the deposits seems to be correlated to the nature of drug. Although the incidence of spoliation in real clinical situations is much lower than suggested by this extreme-case in vitro simulation, topical therapy after implantation of AlphaCor should be carefully considered, kept to the minimum required, and additive-free where possible.

Objective: Thousands of Americans are prescribed cervical orthoses each year. These orthoses restrict motion, which may influence the patient's driving performance. No legal restrictions exist that prohibit patients from wearing cervical orthoses while driving. No study addressing this issue has been published to date. Thus, we sought to assess the effects of wearing a restrictive neck brace on driver performance on the open road., Methods: We conducted a prospective, randomized block design study in 23 volunteers. Twenty-three adult licensed drivers from the state of Iowa were recruited. Evaluation of neck motion was performed with and without the rigid cervical orthosis. On-road performance testing was conducted with the use of a state-of-the-art mobile laboratory. Drivers were randomly assigned to one of two testing groups. Each driver was evaluated during two separate drives. Volunteers in Group A (n = 11) wore a neck brace for the first drive but not during the second. Participants in Group B (n = 12) did not wear a neck brace in the first drive but did for the second. The assessment included velocity, acceleration, cervical axial rotation, and evaluation of the driver's blind spot., Results: Driving performance measures were collected and analyzed for both drives. Wearing a cervical orthosis resulted in decreased velocity (P < 0.05), decreased lateral acceleration (P < 0.05), decreased axial rotation (P < 0.05), inadequate evaluation of intersection traffic, and an increase in the blind spot., Conclusion: A rigid cervical orthosis alters driver performance.

We report a case of a displaced laser in situ keratomileusis flap. The flap displacement was enhanced by using cross-polarized filters.

The case is presented of metastatic carcinoma to the retina in a 63-year-old woman with known disseminated large bowel carcinoma. The clinical appearance and angiographic features are discussed.

The medical care of prisoners is a difficult and often costly process. Basic medical needs are serviced by prison medical officers. However, specialized care often means transport to specialist centers with the attendant cost and safety. We examined portable ophthalmic equipment in a prison environment to screen 11 prisoners who were scheduled for specialist ophthalmic assessment. Medical and ophthalmic histories were documented, visual acuity was tested, digital images were taken of the external eye and retina, and intraocular pressures taken. The data were sent via modem to a specialist ophthalmologist, and the reports were dictated via e-mail at the end of each session. Of the 11 patients who were scheduled to travel for ophthalmic assessment, only 2 were still required to travel to a specialist ophthalmic center. This pilot study showed that there were considerable cost savings to be made by this screening process with the attendant increase in community safety. The prototype equipment requires refinement by further experimentation, but showed the potential as an adjunct to current examination and assessment techniques when applied to a prison population.

In prisons, prison medical officers provide general medical care. However, if specialist care is needed then the prisoner is transported to a specialist medical centre. This is a costly procedure and prison escapes occur during transportation. We have tested our Internet-based eye care system in prisons in Western Australia. Medical and ophthalmic history, visual acuity and intraocular pressure were stored in a browser-based multimedia database. Digital images of the retina and the external eye were recorded and transmitted to a central server. Based on the medical data and the digital images, the specialist ophthalmologist could provide a diagnosis within 24 h. Eleven patients (mean age 48, range 30-82 years) were reviewed during two separate visits to a maximum-security prison in Western Australia. Our main aim was to train prison medical officers and nurses to operate the portable ophthalmic imaging instruments and to use the Internet-based eye care system. The outcome of the pilot study indicated that considerable savings could be made in transport costs and the security risk could be reduced. The Ministry of Justice in Western Australia has decided to implement telemedicine services to provide regular ophthalmic consultation to its prisons.

Photographs of the optic nerve head (optic disc) in the eye are used for the clinical assessment of the disease glaucoma. These images are usually subjectively assessed by a clinician. A case of Sturge-Weber Syndrome which includes glaucoma as a symptom, is presented here. Narrowing of the rim of the optic disc was measured using custom-made measurement software confirming glaucomatous progression. To maximize the information obtained from optic disc images, low cost software can assist with quantifying disc parameters aiding clinical interpretation.

Purpose: To investigate image compression of digital retinal images and the effect of various levels of compression on the quality of the images., Methods: JPEG (Joint Photographic Experts Group) and Wavelet image compression techniques were applied in five different levels to 11 eyes with subtle retinal abnormalities and to 4 normal eyes. Image quality was assessed by four different methods: calculation of the root mean square (RMS) error between the original and compressed image, determining the level of arteriole branching, identification of retinal abnormalities by experienced observers, and a subjective assessment of overall image quality. To verify the techniques used and findings, a second set of retinal images was assessed by calculation of RMS error and overall image quality., Results: Plots and tabulations of the data as a function of the final image size showed that when the original image size of 1.5 MB was reduced to 29 KB using JPEG compression, there was no serious degradation in quality. The smallest Wavelet compressed images in this study (15 KB) were generally still of acceptable quality., Conclusions: For situations where digital image transmission time and costs should be minimized, Wavelet image compression to 15 KB is recommended, although there is a slight cost of computational time. Where computational time should be minimized, and to remain compatible with other imaging systems, the use of JPEG compression to 29 KB is an excellent alternative.

The objective was to evaluate digital images of the retina from a handheld fundus camera (Nidek NM-100) for suitability in telemedicine screening of diabetic retinopathy. A handheld fundus camera (Nidek) and a standard fundus camera (Zeiss) were used to photograph 49 eyes from 25 consecutive patients attending our diabetic clinic. One patient had cataracts, making it impossible to get a quality image of one of the eyes (retina). The Nidek images were digitized, compressed, and stored in a Fujix DF-10M digitizer supplied with the camera. The digital images and the photographs were presented separately in a random order to three ophthalmologists. The quality of the images was ranked as good, acceptable or unacceptable for diabetic retinopathy diagnosis. The images were also evaluated for the presence of microaneurysms, blot hemorrhages, exudates, fibrous tissue, previous photocoagulation, and new vessel formation. kappa Values were computed for agreement between the photographs and digital images. Overall agreement between the photographs and digital images was poor (kappa < 0.30). On average, only 24% of the digital images were graded as being good quality and 56% as having an acceptable quality. However, 93% of the photographs were graded as good-quality images for diagnosis. The results indicate that the digital images from the handheld fundus camera may not be suitable for diagnosis of diabetic retinopathy. The images shown on the liquid crystal display (LCD) screen of the camera were of good quality. However, the images produced by the digitizer (Fujix DF-10M) attached to the camera were not as good as the images shown on the LCD screen. A better digitizing system may produce better quality images from the Nidek camera.

The neuroretinal rims of a set of glaucoma patients were measured using digitized stereo photographs, to determine the reproducibility of computerized stereo measurements of the neuroretinal rim. Each rim was measured five times at 18 locations, with measurement error (ME) defined as the mean of standard deviations of each set of measurements. The following ME were determined: (i) inter-sessional variability (n = 27 right and 24 left eyes, at t1 and t2); (ii) inter-assessor variability (n = 9, 2 assessors); and (iii) variability after colour adjustment algorithms were applied (n = 15). The results were as follows: (i) inter-sessional variability was 3.41+/-1.08 for t1 and 3.22+/-0.84 for t2; (ii) there was a significant difference between the two assessors, although the ME was still low; and (iii) there was no significant differences between the ME of unadjusted and adjusted images. With a measurement error of up to 11% of rim width, these results show that lowcost rim measurements can be made using PC-based software.

Aim: To assess serial, simultaneous stereo optic disc images by four methods for glaucomatous progression., Methods: Using varying techniques, two ophthalmologists assessed serial optic disc images of 52 eyes from 27 patients with a mean duration between images of 18 months. The neuroretinal rim width was qualitatively assessed by four assessment methods and compared with quantitative rim measurements made using PC based software., Results: The highest sensitivity of 83% was achieved using computerised stereo chronoscopy., Conclusion: Stereo chronoscopy improved the detection of subtle optic disc changes when compared with simpler assessment techniques.

A digital indirect ophthalmoscope (DIO) was developed and tested for use in tele-ophthalmology screening for posterior and anterior segment diseases. Using custom software, images from the DIO were digitized, compressed, stored and transmitted to a centralized eye clinic for interpretation. A total of 43 subjects were primarily screened for glaucoma using the DIO, a hand-held fundus camera and a stereo fundus camera. The photographic slides from the stereo fundus camera used as gold standards. Images (390 x 300 pixels x 3 bits) were stored using a laptop computer together with patient information. Image quality received at the central eye clinic was good and showed adequate diagnostic information. An ophthalmologist estimated cup-disc ratios and graded the quality of the images. The sensitivity and specificity of each instrument was calculated. A high sensitivity and specificity was found when using the DIO, indicating that it could be used in tele-ophthalmic screenings. Further modifications are needed to make the instrument more user-friendly and to enable it to be used with undilated pupils, so that it can be easily operated by health-care personnel in remote areas. The camera can also be used to image gross external eye pathology.

We describe two patients who had episodic elbow snapping and ulnar nerve dysesthesias only after weightlifting. These symptoms would disappear soon afterward. The episodic nature of their complaints and findings led to misdiagnosis. We documented by repeated clinical examinations and magnetic resonance imaging that the presence of these symptoms correlated directly with the finding of intermittent, activity-related snapping of the medial triceps. In both patients, the symptoms disappeared when the medial portion of the triceps migrated medially but did not dislocate over the medial epicondyle with elbow flexion. Thus, a minor change in the configuration of the medial portion of the triceps (fluid accumulation) in the same individual at different times can cause intermittent dislocation of the medial triceps. Previous papers dealing with patients with snapping of the medial triceps describe symptoms exacerbated by athletic activities, but the constant finding of snapping on sequential examinations.

Purpose: The digital images of the optic disk from a portable fundus camera were evaluated for suitability in teleophthalmologic screening for glaucoma., Methods: Fifty-one eyes of 27 consecutive patients from our glaucoma clinic were dilated and photographed with a Zeiss FF retinal camera (Carl Zeiss, Oberkochen, Germany) and a portable Nidek NM-100 (Nidek, Tokyo, Japan) fundus camera. Digital images from the portable fundus camera were digitized, compressed and stored in a Fujix DF-10M (Fuji, Tokyo, Japan) digitizer. Lossy compressed digital images and photographs from the Zeiss camera were presented separately in random order to three ophthalmologists for estimation of vertical cup:disk ratios (VCDR) and to evaluate image quality as good, acceptable, or unacceptable for screening glaucoma. Gold standard VCDRs were measured from monoscopic photographic slides obtained using the Zeiss camera by a fourth ophthalmologist., Results: Measurement of agreement (Kappa values) between estimated VCDR of digital images and photographs by the three ophthalmologists were 0.52, 0.38, and 0.50 respectively. Agreement between gold standard and estimated VCDR from photographs were 0.87, 0.45, and 0.84 respectively (specificity between 79% and 97%, sensitivity between 70% and 95%). Kappa values obtained between gold standard and estimated VCDR from digital images were 0.52, 0.49, and 0.49, respectively (specificity between 68% and 79%, sensitivity between 67% and 87%., Conclusion: Moderate to good agreement indicates that the digital images from the portable fundus camera may be suitable for optic disk assessment in the current configuration. This easy to use Nidek hand-held camera could be a viable instrument for teleophthalmology if a better digitizing system is incorporated to improve the quality of the images.

Background: Bartonella henselae has been identified as the causative agent of the neuroretinitis associated with cat scratch disease (CSD). Immunofluorescent antibody tests with good sensitivity and specificity are available to aid in diagnosis. Despite diagnostic advances, optimal management remains controversial. We present a case of documented B. henselae macular neuroretinitis managed without antibiotics and discuss antibiotic use in this condition., Methods: We examined a young woman with macular neuroretinitis and established a diagnosis of CSD. Management consisted of a review of the literature, followed by educating her about the condition and close observation. We documented the course of her disease., Results: We diagnosed neuroretinitis associated with B. henselae infection based on immunofluorescent antibody titres and clinical presentation. Our patient's neuroretinitis resolved promptly without antibiotic therapy., Conclusions: Macular neuroretinitis in CSD can be satisfactorily diagnosed with the use of fluorescent antibodies in the appropriate clinical setting. Optimal treatment for the disease has not been established and observation combined with patient education remains an appropriate option. The self-limited nature of the disease implies that treatment studies not using controls must be interpreted with great caution. Adverse drug reactions and other iatrogenic complications can be reduced by limiting antibiotic use in settings where a meaningful treatment benefit has not been established.

Two ophthalmic case histories requiring differing techniques to document the long-term outcomes of ocular tumours are presented. In the first case, after documenting a treated choroidal melanoma it was necessary to intervene with digital manipulation to enhance the images for clinical interpretation. Conversely, after documenting an iris tumour over an eight-year period, it was considered that the original images were suitable for interpretation without intervention. This raises the issue of images presented as legal evidence when digital technology is used to manipulate and enhance the images. Are these images admissible as evidence in court, and should the original data also be archived to prevent conflicting interpretations by the legal system? In light of The House of Lords recommendations on digital images as evidence, it is suggested that both the manipulated and original images are archived to avoid debate on the extent to which an image has been altered.

The purpose of this study was to evaluate recombinant adeno-associated virus (AAV) as an in vivo gene transfer vector for the retina and to explore the possibility of monitoring the expression of green fluorescent protein (GFP) using a noninvasive method. Rats were injected subretinally with rAAV-gfp or rAAV-lacZ. Strong expression of the reporter gene in a circular area surrounding the injection site was observed in retinal whole mounts and tissue sections. Higher magnification revealed that cells demonstrating high levels of green fluorescence were hexagonal in shape, indicating they were retinal pigment epithelium (RPE) cells. Histological observation of retinal sections demonstrated that recombinant AAV specifically transduced RPE cells. Ten animals were injected with rAAV-gfp for longitudinal studies and the fluorescence was monitored by retinal fluorescence photography. The GFP signal was detected in 100% of the animals as early as 2 weeks postinjection and remained present throughout the experimental period of 4 months. After 2 weeks, a gradual increase in the number of transduced cells occurred before reaching maximal levels of GFP expression at 8 weeks. This was followed by a small decrease over 4 weeks before reaching stable expression at 16 weeks. Our results demonstrated that rAAV efficiently transduces rat RPE cells and that retinal fluorescence photography is suitable for monitoring GFP expression. By using this noninvasive technique, we demonstrated that repetitive measurements of GFP expression in vivo in the rAAV-gfp-transduced retina are possible. This study demonstrated that retinal fluorescence photography is a potent tool for studying AAV-mediated gene delivery in the retina.

Background: Publications on changes of optic disc topography usually illustrate their findings with two-dimensional images., Methods: With the introduction of computerized imaging, anaglyphs of stereo images can be produced for illustrations. Anaglyphs are viewed three-dimensionally with red-green spectacles that are included in refraction sets and are normally used to assess phoria. An anaglyph of progressive, glaucomatous progression is included to demonstrate the method, along with conventional colour images., Results: We present two cases of severely altered optic disc topography post-trabeculectomy and illustrate these cases with anaglyphs that can be viewed three-dimensionally., Conclusion: Three-dimensional viewing of illustrations assists with the visualization, perception and interpretation of optic disc changes.

Aims: To investigate the longevity and reproducibility of choroidal neovascularisation (CNV) induced by krypton laser photocoagulation in the rat. The presence of cell adhesion molecules (CAMs) and vascular endothelial growth factor (VEGF) during the development of CNV was also studied., Methods: 67 pigmented rats underwent retinal photocoagulation by krypton laser. The eyes were examined by either single or serial fluorescein angiography at 3 days, 1, 2-3, 4-5, 7-8, and 12 weeks post photocoagulation. The expression of CAMs (ICAM-1, E-selectin, and CD44) and VEGF post photocoagulation was studied by immunohistochemistry., Results: CNV related fluorescein leakage appeared in 46.4% of 766 laser spots delivered to the 58 eyes that were tested at 2-3 weeks post treatment. The ratio of hyperfluorescent laser sites did not change significantly at 8 weeks post laser. The number of leaky spots was independent of the total number of lesions delivered to each eye (at 2-3 weeks post laser 10-15 spots/eye: 44% and 25-30 spots/eye: 49%; t = 0.7673; p = 0.3903). Nine eyes were followed by serial angiography between 2 and 12 weeks. The laser spots with fluorescein leakage at 2 weeks (51.5%) remained leaky at 12 weeks (51.5%). Histopathologically, macrophage accumulation peaked at 5 days and CNV was firstly observed at 1 week post photocoagulation. ICAM-1, E-selectin, CD44, and VEGF were maximally induced at 3-5 days post laser photocoagulation, and were localised to RPE, choroidal vascular endothelial, and inflammatory cells. VEGF was also detected in intravascular leucocytes at the sites of laser lesions., Conclusions: These studies demonstrated that krypton laser photocoagulation can be successfully used to produce lesions similar to those of human CNV. The response induced remained present for an extended period of time (12 weeks), thus offering a potential model to screen candidate CNV inhibitory agents. In addition, it is proposed that the expression of ICAM-1, E-selectin, CD44, and VEGF before new vessel formation might be linked to the initiation of CNV.

Purpose: Quantifying neuroretinal rim width from optic disc photographs to study glaucomatous progression requires precise, reproducible measurements. We explored the use of a personal computer with three-dimensional capabilities to enhance measurement accuracy and repeatability., Methods: A simultaneous stereo retinal camera was used to serially photograph the optic discs often glaucomatous eyes with a mean interval of 18 months. The neuroretinal rims were qualitatively assessed as either stable (five) or narrowing (five). The images were measured using software written for an IBM compatible personal computer The measurements were compared from the earliest to the most recent image and the five narrowed rims were correctly identified., Results: This simple, low-cost method allowed both three-dimensional viewing and measurement of the optic disc rim from simultaneous stereo images., Conclusions: This method is, potentially, more sensitive in identifying glaucomatous rim changes than conventional, subjective image comparison techniques.

Objective: Branch retinal vein occlusions (BRVOs) are known to occur most commonly in the vicinity of arteriovenous (A/V) crossings. The authors aimed to identify types of venous wall abnormalities in BRVO and document their position in relation to the A/V crossing., Design: A retrospective review of the color photographs and fluorescein angiograms from the most recent 110 patients with first- or second-order BRVO was performed., Main Outcome Measures: The films were examined for the presence of angioarchitectural changes of specified type within one-quarter disk diameter of the A/V crossing involved in the BRVO. The specific changes noted were fluorescein leakage, presumed thrombi, and flow abnormalities, which were recorded along with their position in relation to the A/V crossing., Results: Of the 110 patients diagnosed with BRVO, 59 had photography of satisfactory quality. Forty-one (70%) of these 59 patients had venous lesions, of which significantly more (chi-square -5.74, P < 0.02) were downstream (56%) than upstream (12%) from the A/V crossing. Thirty-two percent were upstream and downstream. Of the hemodynamic changes seen, 49% had late venous phase leakage of fluorescein, 85% had abnormal flow, and 7% had presumed thrombi. All thrombi seen were downstream., Conclusions: Venous lesions in the vicinity of the A/V crossing commonly are seen in BRVO, most of which occur downstream. This suggests that the venous narrowing at the crossing may induce downstream hemodynamic changes predisposing to endothelial damage and thrombus generation.

Objective: To compare the Zeiss retinal camera with the Nidek 3-Dx camera for photographic quality and stereo separation., Subjects: Eleven subjects (22 eyes) were selected from patients referred for optic disc photography., Methods: The subjects were photographed using the Nidek 3-Dx camera for simultaneous stereo photographs, and the 30 degrees field and 15 degrees field settings on the Zeiss retinal camera for sequential stereo photographs. Four ophthalmologists qualitatively scored the photographs on a five-point scale for stereo separation and photographic resolution and sharpness. The results from the four observers were averaged and the Friedman two-way analysis of variance used to analyse the results., Conclusions: It was found that the stereo separation is significantly better using the Nidek camera when compared with both the 30 degrees and 15 degrees Zeiss results. There was no significant difference in photographic quality between the Nidek and Zeiss 30 degrees photographs. It was also found that the Zeiss 30 degrees images had a significantly higher quality than the Zeiss 15 degrees, which contradicted previous results.

Of all the diseases of the eye, the retinal disorders are perhaps the most frequently misdiagnosed by the general medical community. The content of this article is restricted to retinal diseases and the importance of symptoms and signs in their accurate diagnosis.

Optic disc and retinal nerve fibre layer (RNFL) photography have been an integral part of the routine screening of glaucoma patients, ocular hypertensives and glaucoma suspects in Perth since 1979. During this period 60 degrees, 40 degrees, 30 degrees and 8 degrees angles of view were examined for potential use in RNFL photography. The degree of dilation and media opacity is highly variable in glaucoma patients because of the age group involved and the miotic therapy. It was found that the 30 degree angle of view gave the most consistent results for routine RNFL photography. Ocular hypertensives tended to be of a lower mean age and 40 degrees wide angle photography was possible but required two different photographic techniques and was not continued. Both 60 degrees and high-magnification RNFL photography are currently used only with selected patients for teaching and demonstration. A modified Hasselblad 120 roll film camera was used for high-resolution RNFL photography. The Hasselblad adaptors, high-resolution results and comparisons with wide-angle RNFL photographs are illustrated in this paper.

Objective: To compare image measurements of the retina produced by scanning laser ophthalmoscopy with those from red-free photographs (RFP) of the nerve fibre layer., Subjects: The left eyes of 23 subjects (10 normal, 7 glaucoma suspect and 6 glaucomatous) were included in this study., Method: All the eyes were photographed using standard red-free photography, and images of the retina were digitised directly from the SLO., Results: The correlation coefficient for all except three subjects was > 0.45, and the probability (p) that R = 0 was < 0.05 in all but 5 eyes., Conclusions: The data indicate that variations in retinal surface reflectivity as measured by the SLO are similar to those recorded on negative film during RFP. This further suggests that the SLO can be useful for making objective measurements of the RNFL, without the intermediate and variable steps of photography.

Retinal nerve fibre layer (RNFL) photography is an established and integral tool in the management of ocular hypertensives and glaucoma suspects, and in assessing the management of glaucoma in an ophthalmic practice. When RNFL negatives are viewed for analysis, high-contrast negatives yield the most information. When positive prints are subsequently requested, the RNFL negatives are difficult to print. The use of an unsharp mask facilitates the transfer of all the high-contrast negative density range to the print. The use of an unsharp mask has been simplified so that it is quick and efficient and can be adapted for high-contrast negatives other than RNFL images.