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Biomedical subjects

Baljean Dhillon

Publications and source records attributed to Baljean Dhillon.

At least 19 recordsLinked to original sources

The eye at altitude.

High altitude retinopathy (HAR) was first described in 1969 as engorgement of retinal veins with occasional papilloedema and vitreous hemorrhage. Since then various studies have attempted to define the incidence, etiology and significance of this phenomenon, usually with small numbers of subjects. Recently studies on relatively large groups of subjects in Nepal, Bolivia and Tibet have confirmed that the retinal vasculature becomes engorged and tortuous in all lowlanders ascending above 2500m. Sometimes this leads to hemorrhages, cotton wool spots and papilloedema, which is the pathological state better known as high altitude retinopathy. These studies have also shown a significant change in both corneal thickness and intraocular pressure at altitude. The retinal blood vessels are the only directly observable vascular system in the human body and also supply some of the most oxygen-demanding tissue, the photoreceptors of the retina. New techniques are being applied in both hypobaric chamber and field expeditions to observe changes in retinal function during conditions of hypobaric hypoxia. This work allows better advice to be given to lowlanders traveling to altitude either if they have pre-existing ocular conditions or if they suffer from visual problems whilst at altitude. This especially applies to the effect of altitude on refractive eye surgery and results of recent studies will be discussed so that physicians can advise their patients using the latest evidence. Retinal hypoxia at sea level accounts for the developed world's largest cause of blindness, diabetic retinopathy. The investigation of retinal response to hypobaric hypoxia in healthy subjects may open new avenues for treatment of this debilitating disease.

Adolescent↗

Transpupillary thermotherapy for the treatment of occult CNV in age-related macular degeneration: a prospective randomized controlled pilot study.

PURPOSE: To evaluate whether transpupillary thermotherapy (TTT) reduces the risk of moderate visual loss in patients with occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: A group of 25 patients were recruited and randomized into TTT or placebo groups. Patients were included if they had a subfoveal purely or predominantly (> 50%) occult CNV secondary to AMD with best corrected visual acuity (BCVA) of 6/60 or better and the lesion was not larger than 4.5 mm. Treatment was carried out using an 810-nm Oculight diode laser with a fixed spot size covering the whole lesion according to the standard protocol. The same procedure was used for the control group, except that the power was set at zero. The patients were followed up at 6 weeks, 3 months and then every 6 months for up to 2 years. A maximum of three treatments were administered in both groups if there was evidence of persistent leakage from CNV. RESULTS: At the 12-month follow-up, there was no significant difference in the mean values for BCVA distance and near or contrast sensitivity between the treatment and control groups. The Mann-Whitney test was used to assess the differences in BCVA and contrast sensitivity between the groups, both at baseline and at the 12-month follow-up. No statistically significant difference was found; both groups lost on average two lines of BCVA. CONCLUSION: Transpupillary thermotherapy appeared to have been of no benefit in preventing further visual loss in patients with occult CNV in this pilot study.

Aged↗

Increased apoptosis and abnormal wound-healing responses in the heterozygous Pax6+/- mouse cornea.

PURPOSE: Corneal wound healing involves a cascade of interactions between the epithelium and stroma. Pax6 is upregulated, and early events include epithelial cell migration and apoptosis of superficial keratocytes. The mouse heterozygous Pax6 (Pax6+/-) corneal phenotype mimics human aniridia-related keratopathy (ARK), and some aspects of wound healing have been shown to be abnormal, including matrix metalloproteinase (MMP)-9 expression. The purpose of this study was to test whether the Pax6+/- genotype affects corneal wound-healing responses, including stromal cell apoptosis, epithelial cell migration rate, and MMP secretion in culture. METHOD: Pax6+/- and wild-type (Pax6+/+) mice were killed and their corneas wounded by epithelial debridement. Whole eyes were cultured in organ culture and corneal epithelial healing rates and keratocyte apoptosis were quantified by topical fluorescein staining and TUNEL, respectively. Dissociated corneal epithelial cells from Pax6+/- and wild-type mice were cultured, and the activities of secreted MMP-9 were determined by zymography. RESULTS: Wound-healing rates during the first 6 hours were significantly faster for larger wounds and for Pax6+/- corneas. Compared with wild-type, wounded Pax6+/- eyes showed significantly more stromal cell apoptosis, and cultured Pax6+/- corneal epithelial cells produced lower MMP-9 activity. CONCLUSIONS: The cumulative effect of abnormal wound-healing responses, characterized by increased stromal cell apoptosis and reduced levels of MMP-9 secretion may contribute to the corneal changes in the Pax6+/- mice. Possible contributions of elevated stromal cell apoptosis and other abnormal wound-healing responses to ARK are discussed.

Animals↗

Asymmetry of retinal arteriolar branch widths at junctions affects ability of formulae to predict trunk arteriolar widths.

PURPOSE: To describe a revised formula for the estimation of retinal trunk arteriole widths from their respective arteriolar branch widths that improves the summarizing of retinal arteriolar diameters. METHODS: A group of young, healthy individuals underwent retinal photography and arteriolar and venular branching points were identified. Vessel widths of the vessel trunks and their branches were determined. The relationship between the branching coefficient (BC; quotient of the area of the branch and trunk vessels) and the asymmetry index (AI) of the vessel branches was explored. The result was used to formulate a new BC. To test the new BC, a second group of young, healthy individuals also underwent retinal photography. Arteriolar branching points were identified, and the trunk and branch arteriolar widths were recorded. This "revised" BC was compared against the gold standard of the BC as a constant value (1.28), as well as a theoretical formula for the BC that includes the angle between the two vessel branches. RESULTS: The BC of arterioles (but not venules) related to the AI (R = 0.275, P = 0.0001; BC arterioles = 0.78 +/- 0.63 . AI). In the second group, the mean arteriolar trunk diameter was 15.56 pixels. The linear regression model for the arteriolar BC was superior to the BC constant of 1.28 (mean difference between estimated and calculated trunk vessel width was 2.16 vs. 2.23 pixels, respectively). The model based on the angle between the branch arterioles was the least accurate (3.43 pixels). CONCLUSIONS: A revised formula has been devised for the arteriolar BC using a linear regression model that incorporates its relationship to the AI. Further studies using this refined formula to calculate the BC are needed to determine whether it improves the ability to detect smaller associations between the retinal vascular network and cardiovascular disease.

Adult↗

Postoperative IOP prophylaxis practice following uncomplicated cataract surgery: a UK-wide consultant survey.

BACKGROUND: In order to minimise postoperative intraocular pressure (IOP) rise, after routine uncomplicated cataract surgery, prophylaxis may be adopted. Currently, there are no specific guidelines in this regard resulting in wide variation in practice across the UK. We sought to document these variations through a questionnaire survey. METHODS: A questionnaire was sent to all consultant ophthalmic surgeons in the UK. RESULTS: 62.6% of surgeons did not use any IOP lowering agents. 37.4% surgeons routinely prescribed some form of medication. The majority (86.8%) used oral diamox. 20.6% of surgeons said they based their practice on evidence, 43.3% on personal experience, and 17.6% on unit policy. Surprisingly, among the two groups of surgeons (those who gave routine prophylaxis, and those who did not) the percentages of surgeons quoting personal experience, unit policy, or presence of evidence was strikingly similar. The timing of the first postoperative IOP check varied from the same day to beyond 2 weeks. Only 20.2% of surgeons had ever seen an adverse event related to IOP rise; this complication is thus very rare. CONCLUSION: This survey highlights a wide variation in the practice and postoperative management of phacoemulsification cataract surgery. What is very striking is that there is a similar proportion of surgeons in the diametrically opposite groups (those who give or do not give routine IOP lowering prophylaxis) who believe that there practice is evidence based. The merits of this study suggests that consideration must be given to drafting a uniform guideline in this area of practice.

Acetazolamide↗

Retinal image analysis: concepts, applications and potential.

As digital imaging and computing power increasingly develop, so too does the potential to use these technologies in ophthalmology. Image processing, analysis and computer vision techniques are increasing in prominence in all fields of medical science, and are especially pertinent to modern ophthalmology, as it is heavily dependent on visually oriented signs. The retinal microvasculature is unique in that it is the only part of the human circulation that can be directly visualised non-invasively in vivo, readily photographed and subject to digital image analysis. Exciting developments in image processing relevant to ophthalmology over the past 15 years includes the progress being made towards developing automated diagnostic systems for conditions, such as diabetic retinopathy, age-related macular degeneration and retinopathy of prematurity. These diagnostic systems offer the potential to be used in large-scale screening programs, with the potential for significant resource savings, as well as being free from observer bias and fatigue. In addition, quantitative measurements of retinal vascular topography using digital image analysis from retinal photography have been used as research tools to better understand the relationship between the retinal microvasculature and cardiovascular disease. Furthermore, advances in electronic media transmission increase the relevance of using image processing in 'teleophthalmology' as an aid in clinical decision-making, with particular relevance to large rural-based communities. In this review, we outline the principles upon which retinal digital image analysis is based. We discuss current techniques used to automatically detect landmark features of the fundus, such as the optic disc, fovea and blood vessels. We review the use of image analysis in the automated diagnosis of pathology (with particular reference to diabetic retinopathy). We also review its role in defining and performing quantitative measurements of vascular topography, how these entities are based on 'optimisation' principles and how they have helped to describe the relationship between systemic cardiovascular disease and retinal vascular changes. We also review the potential future use of fundal image analysis in telemedicine.

Animals↗

Effect of axial length on retinal vascular network geometry.

PURPOSE: To explore the association between axial length and retinal vascular network geometry (arteriovenous diameter ratio [AVR], arteriolar branching angles, and junctional exponents). DESIGN: Prospective, cross-sectional study. METHODS: Patients were recruited from a pseudophakic population that had preexisting axial length measurements. Mean arterial blood pressure and previous medical history were recorded. Fundal photographs were taken. Digital image analysis was used to determine the AVR, mean arteriolar bifurcation angle, and junctional exponent for each subject. RESULTS: In total, 52 subjects were analyzed. Axial length had no association with AVR (R = -0.01, P = .941), mean angles at arteriolar bifurcations (R = -.134, P = .342), or junctional exponents (R = .003, P = .982). However, increased axial length was associated with a trend for lower measured retinal venular and arteriolar diameters (R = -.28, P = .04 and R = -.23, P = .10, respectively). Junctional exponents correlated with both the AVR (R = .32, P = .019) and vascular bifurcation angles (omega) (R = .317, P = .022). CONCLUSIONS: Increased axial length is associated with narrowing of both arteriolar and venular diameters, but not on the AVR, or vessel junctions. Future studies exploring the influence of systemic disease on retinal vascular topography do not need to consider axial length as a potential confounding variable when utilizing measures such as AVR or vessel junctions. Vascular arteriolar junctional exponents may serve as a good measure of overall altered retinal vascular geometry in cardiovascular disease.

Adult↗

Long anterior lens zonules in late-onset retinal degeneration (L-ORD).

PURPOSE: We report new findings of peripupillary iris atrophy and long anteriorly-inserted zonules in a family with late-onset retinal degeneration (L-ORD). DESIGN: The proband was noted to have anterior segment findings not previously described in L-ORD, an autosomal dominant condition resulting in severe visual impairment. A mutation in the C1QTNF5 (CTRP5) gene is causal. We identified family members with anterior segment findings. METHODS: Family members were examined with slit-lamp biomicroscopy and psychophysical tests including dark adaptation and visual fields. Genetic testing for the C1QTNF5 mutation was carried out. RESULTS: In this family with a proven mutation in this gene, peripupillary iris atrophy and abnormally long anterior zonular insertions were present before retinal changes and visual loss. CONCLUSIONS: Anterior segment findings have not previously been reported and along with impaired dark adaptation may serve as an early marker for this condition thus facilitating counseling and possible therapeutic intervention.

Atrophy↗

Developmental and cellular factors underlying corneal epithelial dysgenesis in the Pax6+/- mouse model of aniridia.

Heterozygosity for a PAX6 deficiency (PAX6+/-) results in low levels of the PAX6 transcription factor and causes aniridia. Corneal changes in aniridia-related keratopathy (ARK) include peripheral pannus and epithelial abnormalities, which eventually result in corneal opacity and contribute to visual loss. The corneal abnormalities of Pax6+/- mice provide an excellent model for the corneal changes seen in PAX6+/- humans. The aim of the present study was to investigate the contributions of different factors (including altered cell proliferation, abnormal epithelial differentiation and incursion of the conjunctival epithelium) that may underlie the pathogenesis of the corneal changes caused by low levels of Pax6 in heterozygous Pax6+/Sey-Neu (Pax6+/-) mice. BrdU incorporation showed enhanced proliferation of Pax6+/- corneal epithelium compared to wild-type controls and analysis of p63 (a marker of high proliferative potential) revealed a slight increase in frequency of p63-positive basal corneal epithelial cells in Pax6+/- mice. Immunohistochemical investigation of K12 (a Pax6-regulated marker of corneal epithelial differentiation) in 2-52-week-old mice showed that K12 expression was delayed and down-regulated in the Pax6+/- corneal epithelium, implying that differentiation of the Pax6+/- corneal epithelium was delayed and abnormal. Goblet cells were identified within the peripheral corneal epithelium of the Pax6+/- eyes, but some were surrounded by cells expressing K12, suggesting they may have arisen in situ in the corneal epithelium. These findings suggest that low levels of Pax6 may be directly responsible for failure or delay of proper differentiation of the corneal epithelial cells, but the proliferative component of the mutant epithelium is probably not impaired. This abnormal differentiation suggests that ARK is not entirely attributable to a limbal stem cell deficiency.

Animals↗

Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures.

The retinal and cerebral microvasculatures share many morphological and physiological properties. Assessment of the cerebral microvasculature requires highly specialized and expensive techniques. The potential for using non-invasive clinical assessment of the retinal microvasculature as a marker of the state of the cerebrovasculature offers clear advantages, owing to the ease with which the retinal vasculature can be directly visualized in vivo and photographed due to its essential two-dimensional nature. The use of retinal digital image analysis is becoming increasingly common, and offers new techniques to analyse different aspects of retinal vascular topography, including retinal vascular widths, geometrical attributes at vessel bifurcations and vessel tracking. Being predominantly automated and objective, these techniques offer an exciting opportunity to study the potential to identify retinal microvascular abnormalities as markers of cerebrovascular pathology. In this review, we describe the anatomical and physiological homology between the retinal and cerebral microvasculatures. We review the evidence that retinal microvascular changes occur in cerebrovascular disease and review current retinal image analysis tools that may allow us to use different aspects of the retinal microvasculature as potential markers for the state of the cerebral microvasculature.

Aging↗

Does a small central Nd:YAG posterior capsulotomy improve peripheral fundal visualisation for the vitreoretinal surgeon?

BACKGROUND: To evaluate the effect of Nd:YAG capsulotomy for posterior capsular opacification (PCO) on visualisation of the peripheral fundus with scleral indentation. METHODS: Patients undergoing Nd:YAG capsulotomy for PCO were examined pre- and four weeks post- Nd:YAG capsulotomy. In order to give a quantitative measure of visualisation of the peripheral retina, a novel scalar measurement was developed. Changes in the degree of visualisation following Nd:YAG capsulotomy were calculated. RESULTS: There was a significant improvement in fundal visualisation of the retinal periphery with scleral indentation following Nd:YAG capsulotomy (p = 0.001). CONCLUSION: Peripheral fundal visualisation with scleral indentation improves following a small central Nd:YAG capsulotomy. This finding is important in relation to the detection of peripheral pseudophakic retinal breaks, particularly in those patients deemed at high risk following Nd:YAG capsulotomy.

Aged↗

Safety and efficacy of a dexamethasone anterior segment drug delivery system in patients after phacoemulsification.

PURPOSE: To compare the safety and efficacy of the Surodex dexamethasone anterior segment drug delivery system (Oculex Pharmaceuticals, Inc.) and dexamethasone 0.1% eyedrops (Maxidex) in patients with inflammation after cataract surgery. SETTING: Cataract Service, Department of Ophthalmology, Lothian University Hospitals, Edinburgh, United Kingdom. METHODS: This comparative single-masked parallel-group study comprised 1 eye of 19 patients having phacoemulsification cataract extraction and posterior chamber intraocular lens implantation. The Surodex group had the dexamethasone drug delivery system inserted into the anterior chamber (AC) angle during surgery and was treated with saline eyedrops (Isopto Plain) for 4 weeks. The control group had no drug delivery system or a placebo inserted at surgery and were treated with dexamethasone 0.1% eyedrops for 4 weeks. A Kowa FM-500 laser flare meter was used to objectively measure AC flare, the main outcome measure. Slitlamp biomicroscopy to grade AC flare and cells, intraocular pressure measurement, and corneal endothelial specular microscopy, performed up to 60 days after surgery, were the secondary outcome measures. The Surodex group had safety follow-ups after completion of the initial study period. RESULTS: Both groups had a steady increase in laser flare meter readings postoperatively. The readings peaked at 3 days in the control group and at 7 days in the Surodex group. This was followed by a gradual decline toward baseline values up to 28 days, after which the values remained at a similar level to 60 days in both groups. There were no significant differences in flare meter readings between the groups throughout the study. There were also no significant between-group differences in subjective assessment of intraocular inflammation and in impact on corneal endothelial cell count (P =.67). Surodex remnants persisted up to a mean of 22.0 months +/- 2.5 (SD) postoperatively in 6 eyes (54%). Neither group had a severe adverse event. CONCLUSION: Surodex appeared to be as effective as dexamethasone 0.1% eyedrops in controlling intraocular inflammation after cataract surgery by phacoemulsification, and both methods had a similar safety profile.

Aged↗

Cataract surgery and consent; recall, anxiety, and attitude toward trainee surgeons preoperatively and postoperatively.

PURPOSE: To assess patients' recall of information, anxiety, and attitude toward trainee surgeons immediately after providing consent for cataract surgery and 1 month postoperatively. SETTING: Cataract Clinic, Princess Alexandra Eye Pavilion, Edinburgh, Scotland. METHODS: A questionnaire was administered to 51 patients immediately after their consent was obtained at the preassessment clinic and 1 month postoperatively (50 patients). Anxiety, attitude toward trainee surgeons, and difficulty understanding the cataract surgery consent and information form were assessed using visual analog scales. RESULTS: Nine postconsent patients (18%) and 2 postoperative patients (4%) recalled the risk for major complications. All postconsent and 40 of 47 postoperative patients (85%) who remembered signing the consent form said they believed they were adequately informed. Patients reported little anxiety about surgery; the consent process had no effect on this. Five of 17 postconsent patients (29%) and 7 of 23 postoperative patients (31%) who could not recall being told a trainee might perform their procedure were unhappy; 1 patient in each group (3% and 4%, respectively) who could recall such a discussion were unhappy. CONCLUSIONS: Patient recall of specific details related to cataract surgery was poor immediately after consent was obtained and deteriorated postoperatively. Despite this, most patients reported they were well informed about surgery and had little anxiety. Patients accept the need for surgical training if they recall a discussion of this at the time of consent. If they do not, many are very unhappy regardless of surgical outcome. These findings strongly support an explicit discussion of surgical training as part of the consent process.

Aged↗

Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration.

A primary feature of age-related macular degeneration (AMD) is the presence of extracellular deposits between the retinal pigment epithelium (RPE) and underlying Bruch's membrane, leading to RPE dysfunction, photoreceptor death and severe visual loss. AMD accounts for about 50% of blind registrations in Western countries and is a common, genetically complex disorder. Very little is known regarding its molecular basis. Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder with striking clinical and pathological similarity to AMD. Here we show that L-ORD is genetically heterogeneous and that a proposed founder mutation in the CTRP5 (C1QTNF5) gene, which encodes a novel short-chain collagen, changes a highly conserved serine to arginine (Ser163Arg) in 7/14 L-ORD families and 0/1000 control individuals. The mutation occurs in the gC1q domain of CTRP5 and results in abnormal high molecular weight aggregate formation which may alter its higher-order structure and interactions. These results indicate a novel disease mechanism involving abnormal adhesion between RPE and Bruch's membrane.

Age of Onset↗