congenital disorders; glycosylation; retinopathy
The current study was designed to determine whether intravitreal injection of tacrolimus (FK506) modulates the gene expression of neurotrophic factor‐related molecules in the retina from eyes with induced experimental autoimmune uveoretinitis (EAU) in rats.
Rats were immunised with interphotoreceptor retinoid binding protein peptide (R14) and given intravitreal injection of tacrolimus on day 12 after immunisation. As control, immunised rats received intravitreal injection of vehicle. On day 15 after immunisation, changes in the genetic programme associated with neuroprotection and inflammatory responses in the retinas from both groups were determined by DNA microarray analyses and confirmed by real‐time PCR analyses.
The gene expression of inflammatory responses was markedly reduced in tacrolimus‐treated eyes. Genes for molecules associated with neuroprotection (oestrogen receptor, erythropoietin receptor, gamma‐aminobutyric acid receptor, protein kinase C, glial cell line‐derived neurotrophic factor receptor, fibroblast growth factor and neuropeptide Y receptor) were upregulated in the retinas from tacrolimus‐treated eyes.
Intravitreal injection of tacrolimus modulated the genes related to neuroprotection in the retina during the ongoing process of EAU. This treatment may be useful for the neuroprotection of retina with severe uveitis as well as for immunosuppression in the uveitic eyes.
To establish the sensitivity and reliability of objective image analysis in direct comparison with subjective grading of bulbar hyperaemia.
Images of the same eyes were captured with a range of bulbar hyperaemia caused by vasodilation. The progression was recorded and 45 images extracted. The images were objectively analysed on 14 occasions using previously validated edge‐detection and colour‐extraction techniques. They were also graded by 14 eye‐care practitioners (ECPs) and 14 non‐clinicians (NCLs) using the Efron scale. Six ECPs repeated the grading on three separate occasions
Subjective grading was only able to differentiate images with differences in grade of 0.70–1.03 Efron units (sensitivity of 0.30–0.53), compared to 0.02–0.09 Efron units with objective techniques (sensitivity of 0.94–0.99). Significant differences were found between ECPs and individual repeats were also inconsistent (p<0.001). Objective analysis was 16× more reliable than subjective analysis. The NCLs used wider ranges of the scale but were more variable than ECPs, implying that training may have an effect on grading.
Objective analysis may offer a new gold standard in anterior ocular examination, and should be developed further as a clinical research tool to allow more highly powered analysis, and to enhance the clinical monitoring of anterior eye disease.
The excess risk of bilateral visual impairment (BVI; bilateral visual acuity <0.5) among individuals with amblyopia is an argument for screening for amblyopia, but data are scarce.
The risk was estimated by determining the incidence of BVI in the Rotterdam Study, a population‐based cohort of subjects aged 55 years or over (n = 5220), including 192 individuals with amblyopia (3.7%). Using a multistate lifetable, the lifetime risk and excess period spent with BVI were determined.
The relative risk of BVI for amblyopes was 2.6 (95% confidence interval 1.4–4.5). For individuals with amblyopia, the lifetime risk of BVI was 18%, whereas they lived on average 7.2 years with BVI. For non‐amblyopic individuals, these figures were 10% and 6.7 years, respectively.
Amblyopia nearly doubles the lifetime risk of BVI and affected individuals spent an extra six months with BVI. This study provides data for future cost‐effectiveness analyses.
amblyopia; lifetime risk; visual impairment
eosinophilic; hypotropia; myositis; orbital; ptosis
C‐kit is a transmembrane tyrosine kinase protein thought to play an important role in tumourigenesis. With the development of the compound imatinib mesylate, which specifically inhibits tyrosine kinase receptors, C‐kit has emerged as a potential therapeutic target. This study aims to determine the immunoexpression of C‐kit in retinoblastoma and correlate this expression with histopathological prognostic features.
Eighty‐four paraffin‐embedded retinoblastomas were collected from the Henry C Witelson Ocular Pathology Registry. C‐kit immunostaining was used according to the protocol provided by Ventana Medical System Inc., Arizona. Immunoreactivity was correlated with the presence or absence of invasion into the choroid and optic nerve and the degree of tumour differentiation. Odds ratios were calculated to quantify differences in C‐kit expression between tumours with different patterns of invasion and differentiation.
Twenty‐one slides (25%) were excluded from analysis because of the presence of extensive tissue necrosis or the absence of sufficient optic nerve tissue for analysis. Overall, C‐kit expression was identified in 33/63 specimens analysed (52.38%). Two of the 13 tumours without choroidal or optic nerve invasion (15.4%) were positive for C‐kit. C‐kit expression was seen in 31 of the 50 tumours with extraretinal invasion (62%, p<0.01), 26 of 44 specimens with choroidal involvement (59.9%, p<0.2), and 20 of the 29 with optic nerve involvement (68.96%, p<0.02). Fourteen of 25 moderate or well‐differentiated specimens (56%) and 19 of 38 undifferentiated specimens (50%) displayed positivity for C‐kit (p>0.5).
More than half the retinoblastomas in this study expressed C‐kit. The expression of C‐kit strongly correlated with histopathological features of a worse prognosis including optic nerve and choroidal invasion.
beach lifeguarding; surveillance; rescue; eyesight standards
To determine the incidence, methods of diagnosis, treatment strategies and outcomes for acute retinal necrosis (ARN) in the UK.
A 12‐month active case ascertainment study was carried out between March 2001 and March 2002 to record cases of ARN presenting to ophthalmologists via the British Ophthalmological Surveillance Unit (BOSU) reporting system. Questionnaires were sent to the reporting consultants, requesting data on patient characteristics, presentation, clinical findings, investigations and treatment. Diagnosis was made using the American Uveitis Society diagnostic criteria. Further questionnaires were sent at 2 weeks and 6 months to assess outcome and therapies.
74 cases of ARN were reported by 58 consultants between March 2001 and March 2002. Questionnaires were returned for 49 cases (66.2%), of which 18 (36.7%) were excluded. Of the 31 cases included, 22 (71.0%) were male and 9 (29.0%) were female. The age range was 13 to 85 years (mean 54.3 years). 28 cases (90.3%) were unilateral, with 3 patients (9.7%) presenting with bilateral ARN.
An aqueous or vitreous biopsy was performed in only 18 patients, with one patient having both. Herpes viral DNA analysis was performed on all 19 biopsies, with identification of the viral DNA in 16; results from 3 biopsies were not documented. Varicella zoster virus (VZV) was the commonest cause identified in 10 patients (56%).
Of the 31 subjects, 27 (87.1%) were treated for ARN with systemic antiviral treatment: with intravenous antiviral in 23 cases (85.2%) and oral antiviral in 4 cases (14.8%). 21 of these patients went on to receive oral antiviral maintenance therapy. In addition to antiviral treatment, systemic steroids were given to 16 subjects (51.6%). Surgical intervention for retinal detachment was performed on 5 patients.
During the 12‐month study period, 31 cases of ARN met the diagnostic criteria set by the American Uveitis Society. The incidence in the UK based on this study is approximately 1 case per 1.6 to 2.0 million population per year. We have ascertained that the management of ARN throughout the UK is variable, suggesting that national guidelines would be of benefit.
To determine whether the efficacy of re‐operation for idiopathic full‐thickness macular hole (FTMH) remaining open after initial surgery with internal limiting membrane (ILM) peeling is correlated with macular hole configuration as determined by optical coherence tomography (OCT), macular hole size, macular hole duration before the first operation, or type of tamponade (gas or silicone oil).
A retrospective consecutive interventional case series of 28 patients (28 eyes) with a persisting macular hole after vitrectomy, ILM peel, and gas tamponade. 28 patients underwent repeat surgery involving vitrectomy and gas (n = 15) or silicone oil tamponade (n = 12) or no tamponade (n = 1). Autologous platelet concentrate (n = 22), autologous whole blood (n = 1), or no adjuvant (n = 5) was used. Preoperative OCT was undertaken in all eyes. The main outcome measures were anatomical closure and improvement of best‐corrected visual acuity (BCVA).
Anatomical closure was achieved in 19 of 28 eyes (68%). BCVA improved in 12 eyes, remained unchanged in nine, and worsened in seven. BCVA improved in 11 of 19 eyes with anatomical closure, and in one of eight eyes without closure. Anatomical closure and improvement of BCVA correlated with preoperative macular hole configuration on OCT, with higher rates of closure (18 of 20 eyes versus one of eight eyes, p = 0.001) and greater improvement of BCVA (p = 0.048) in eyes with a cuff of subretinal fluid at the break margin. Macular hole size, type of tamponade, macular hole duration before the first operation, or preoperative BCVA did not significantly correlate with visual or anatomical outcome.
Macular hole configuration seems to be a strong prognostic indicator of anatomical closure and may help identify those patients most likely to benefit from re‐operation.
OCT; macular hole; retreatment
The inadvertent intra‐ocular administration of benzalkonium chloride‐preserved hydroxypropyl methylcellulose during cataract surgery at another hospital in 1999 resulted in toxic corneal endothelial injury and profound postoperative corneal oedema as a result of endothelial decompensation. The long‐term effect of this adverse event was assessed.
All 19 patients were invited to return for examination including corneal endothelial specular microscopy and pachymetry seven years after the incident. Results were compared with data from one year after the incident.
Five patients attended for examination, one had received a penetrating keratoplasty and was, therefore, excluded. Ten patients had died and four had moved out of the region and were unable to attend. All four study patients were pain free and achieved 6/12 or better. Mean central corneal thickness reduced by 13% from 652.6 μm at one year to 563.4 μm. Mean central corneal endothelial cell density (n = 3) increased 28% from 663.7 cells/mm2 at one year to 835.7 cells/mm2 (p<0.05).
After toxic injury, corneal endothelial function may have a remarkable capacity for recovery even after the first postoperative year. The rise in central endothelial cell density may represent cell migration from less affected areas or cellular proliferation. Should this unfortunate event recur, clinicians may expect continued recovery beyond one year.
corneal endothelium; injury; pachymetry; specular microscopy; cataract surgery; benzalkonium chloride
To study the incidence, systemic associations, presenting features and natural history of Purtscher's retinopathy in the UK and Ireland.
Cases were collected prospectively by active surveillance through the British Ophthalmological Surveillance Unit. Clinical details were obtained using an incident questionnaire, with follow‐up at 1 and 6 months.
Clinical details were obtained for 15 cases over 12 months. These were associated with road traffic accidents in 6 cases, chest compression in 6 cases and acute pancreatitis in 3 cases. All cases were symptomatic and presented with loss of visual acuity, visual field or a combination. Bilateral involvement was noted in 9 cases. The acute retinal signs of cotton wool spots, retinal haemorrhage and Purtscher flecken cleared within 1 month in 26% of eyes and within 6 months in all eyes. The most common chronic signs were optic disc pallor and atrophy of the retinal pigment epithelium. Without treatment, 50% of eyes improved by at least 2 Snellen lines at final follow‐up and 23% improved by at least 4 Snellen lines. Only 1 of the 24 eyes had a final acuity worse than that recorded at presentation.
Purtscher's retinopathy is a rare but sight‐threatening eye condition, most commonly seen in young or middle‐aged men and after trauma. Spontaneous visual recovery of at least 2 Snellen lines is seen in half of the cases.
PAM with atypia; Mitomycin; stem‐cell transplant
The Pulfrich phenomenon is a dynamic stereo dysmetropsia attributed to an asymmetry of neural conduction between the eyes. The phenomenon may arise spontaneously with ocular and neurological disease and may be induced in normal subjects by placing a light‐attenuating filter before one eye. By analogy, it is predicted that a localised variation of retinal illumination within one and the same eye should affect the perception of moving targets.
A rotating, nesting square display was generated by computer graphics. The inner square was painted bright white, the outer dim grey. Luminances, rates of rotation and angular sizes were varied.
On rotation, the outer, dimmer square appeared to lag behind the inner, brighter one, as a “lazy shadow”. The lag was measured quantitatively in normal observers by applying a compensatory lead to the lagging square. The magnitude of lag was found to depend on luminance, spin rate and visual angle. Lags exceeding 10° were observed under optimum conditions.
The experimental results confirm the existence of a monocular counterpart to the binocular Pulfrich phenomenon. Distortions of moving images are likely to occur spontaneously with monocular, localised visual field defects.
Quantitative data regarding the impact of neovascular age‐related macular degeneration (NV‐AMD) on individuals and society is a prerequisite for rational decision‐making processes when evaluating alternative treatments for the disease.
75 bilateral NV‐AMD (patients) and 91 elderly non‐AMD (controls) subjects forming the UK cohort of an international cross‐sectional, observational study were independently analysed. Subjects completed a telephone survey including the National Eye Institute Visual Function Questionnaire (NEI‐VFQ‐25), the EuroQol (EQ‐5D), the Hospital Anxiety and Depression Scale (HADS), history of falls and health resource utilisation.
Patients with NV‐AMD reported substantially worse vision‐related functioning and overall well‐being, including higher depression scores, than controls after adjusting for age, gender and co‐morbidities (adjusted mean scores: NEI‐VFQ‐25 overall 52.7 vs 90.7, p<0.0001; EQ‐5D 0.67 vs 0.77, p = 0.0273; HADS depression 6.8 vs 4.0, p = 0.0026). Significantly more patients reported a need for assistance with daily activities compared with controls (25.3% vs 6.6%, p = 0.003). Total annual healthcare utilisation costs were more than sevenfold higher for patients with AMD compared with controls (£3,823.89 vs £517.05, respectively; p<0.0001)
Patients with NV‐AMD show a significant decline in quality of life and increased need for daily living assistance compared to a control population without AMD. With the availability of effective new therapies there is a need for improved early access to treatment.
To examine the determinants of formal and informal care utilisation amongst persons with age‐related macular degeneration (AMD).
Cross‐sectional hospital‐based study.
Hospital eye clinic in Northern Ireland.
284 persons aged ⩾50 years.
Main outcome measures
Participants were questioned about their care, living arrangements, eyesight‐related ability to self‐care, and eyesight‐related need to be more careful whilst undertaking everyday tasks.
The percentage of older persons receiving formal and informal care rose with the level of visual impairment. 34.9% and 37.3% of those with no visual impairment received formal and informal care, respectively, compared with 51.6% and 69.9% of those with moderate visual impairment and 55.6% and 88.9% of those with severe visual impairment. Three factors (age, best corrected distance visual acuity in the better eye and living alone) were significant predictors (p<0.05) of care utilisation. The likelihood of someone utilising formal care rose with increasing age, severity of visual impairment and living alone. There is an approximate one‐to‐one trade‐off between age and visual acuity such that a difference of one line of vision is equivalent to approximately 1 year of life to the affected individual as regards its impact on the probability of care utilisation.
Care utilisation is predicted by age, visual acuity in the better eye and living arrangement. These findings question the validity of the current practice of defining the need for statutory services on the basis of visual acuity alone. These data may have implications for cost utility analyses of new therapeutic developments in macular degeneration.
care utilisation; age‐related macular degeneration; visual impairment