Dexamethasone reverses the effects of high glucose on human retinal endothelial cell permeability and proliferation in vitro.

Diabetic macular oedema (DMO), a leading cause of preventable visual loss in the working population, is caused by an increase in microvascular endothelial cell permeability, and its prevalence is on the increase in parallel with the rising worldwide prevalence of diabetes. It is known that retinal vascular leakage in DMO is contributed to by VEGF upregulation as well as non-VEGF dependent inflammatory pathways, and the potential use of anti-inflammatory agents such as the glucocorticoids, including dexamethasone are being extensively studied. However, the mechanisms of action of dexamethasone in DMO reduction are not fully understood. Using human primary retinal endothelial cells (REC) the in vitro effect of dexamethasone in modulating the proliferation, permeability and gene expression of key tight and adheren junction components, and the expression of angiopoietins (Ang) 1 and 2 in high (25 mM) glucose conditions were investigated. High glucose decreased REC proliferation, an effect that was reversed by dexamethasone. High glucose conditions significantly increased REC permeability and decreased claudin-5, occludin and JAM-A gene expression; dexamethasone was effective in partially reversing these changes, restoring EC permeability to the normal or near normal state. High glucose levels resulted in reduction of Ang1 secretion, although Ang2 levels were consistently high. DEX increased Ang1 and decreased Ang2, indicating that the balance of Ang1/Ang2 may be important in determining functional changes in REC under high glucose conditions.

The effect of hyperglycaemia on permeability and the expression of junctional complex molecules in human retinal and choroidal endothelial cells.

Diabetic retinopathy is the leading cause of preventable blindness in the working population and its prevalence continues to increase as the worldwide prevalence of diabetes grows. Diabetic choroidopathy is less well studied and occurs in the late stages of diabetic eye disease. The main cause of visual loss in diabetic eye disease is diabetic macular oedema caused by an increase in microvascular endothelial permeability. Endothelial cell permeability is influenced by multiple factors which have not been fully elucidated, particularly in human models. In addition, the gene and protein expression between retinal and choroidal endothelial cells, even in humans, has been shown to be heterogeneous. The aim of this project was to determine, in vitro, the effect of high glucose (25 mM) on human paracellular permeability in retinal and choroidal endothelial cells. The expression of selected tight junction molecules (Occludin, Claudin-5, JAM-A and JAM-C) and adheren junction (VE-Cadherin) molecules was also compared between retinal and choroidal endothelial cells and with high glucose. High glucose conditions significantly increased the permeability in both retinal and choroidal endothelial cells monolayers although the increase was higher in retinal endothelial cells. Under normal glucose culture conditions microarray analysis determined that occludin and claudin-5 gene expression was higher in retinal endothelial cells than choroidal endothelial cells, and western blotting indicated that claudin-5 protein expression was also higher in retinal endothelial cells whilst JAM-A, and C and VE-Cadherin levels were similar. In retinal endothelial cells exposed to high glucose claudin-5, occludin and JAM-A was found to be reduced, whereas the expression of VE-Cadherin and JAM-C was unchanged when evaluated with western blotting, immunofluorescence and qPCR. None of the proteins were significantly decreased by high glucose in choroidal endothelial cells. The increase in retinal endothelial cell permeability is likely caused by a decrease in selective tight junction protein expression, leading to increased paracellular permeability. This may indicate differences in junctional molecule regulation of permeability in retinal compared to choroidal endothelial cells.

Prevalence of age-related macular degeneration in an elderly UK Caucasian population-The Bridlington Eye Assessment Project: a cross-sectional study.

ImportanceThere is paucity of data on prevalence and disease asymmetry of age-related macular degeneration (AMD), particularly the earlier stages, in the UK population.Objective and PurposeTo determine the prevalence of age-related macular degeneration in an elderly Caucasian UK population.DesignCross-sectional population study, 2002-2006.ParticipantsResidents in the study area of Bridlington aged 65 years and older.MethodsFull-ophthalmic examination was undertaken in 3549 participants, of eligible 6319 Caucasian population (response rate of 56%). Non-stereoscopic Colour fundus photographs (30°) were graded masked using a modified Rotterdam Classification for 3475 (98%) participants with gradable images. Prevalence for different AMD grades were calculated. Demographic details were analysed then integrated with the AMD gradings for full analysis. Prevalence rates for the different AMD Grades were calculated, as well as the age-specific prevalences.ResultsAMD prevalence in the worst eye were 38.5% grade 0, 41.4% grade 1, 12.8% grade 2, 2.8% grade 3, and 4.6% grade 4. Geographic atrophy (grade 4a) occurred in 2.5%, and neovascular AMD (grade 4b) in 1.8%. Prevalence increased with age such that grade 4 (advanced) AMD was 2.2% in the 65-69 years group, 15.8% for the 85-90, and 21.2% for over 90 years. There was significant asymmetry between the two eyes of individuals with advanced AMD (P<0.001), such that vision loss was unilateral. Persons with more advanced AMD grades were more likely to be dissatisfied with their vision.ConclusionsAdvanced AMD occurs more commonly in the UK Caucasian population than previously reported. Significant asymmetry between the two eyes occurs in individuals with unilateral advanced AMD so that visual impairment statistics do not represent true prevalence of advanced AMD. Persons with more advanced AMD were more likely to be dissatisfied with their vision.

The management of retinal vein occlusion: is interventional ophthalmology the way forward?

Retinal vein occlusions (RVO) are the second commonest sight threatening vascular disorder. Despite its frequency treatments for RVO are unsatisfactory and include several that have not been tested by large, well designed, prospective, randomised controlled trials. There is also the lack of long term follow up in many of the available small uncontrolled studies, and the timings of interventions are haphazard. This review aims to evaluate the current knowledge relating to the pathogenesis, suggested treatments for the different types of RVO, and their complications. Isovolaemic haemodilution is of limited benefit and should be avoided in patients with concurrent cardiovascular, renal, or pulmonary morbidity. Evidence to date does not support any therapeutic benefit from radial optic neurotomy, optic nerve decompression, or arteriovenous crossing sheathotomy on its own. Vitrectomy combined with intravenous thrombolysis may offer promise for central RVO. Similarly, vitrectomy combined with arteriovenous sheathotomy intravenous tissue plasminogen activator may offer benefits for branch RVO. RVOs occur at significantly high frequency to allow future prospective randomised controlled studies to be conducted to evaluate the role of different therapeutic modalities singly or in combination.

Effect of age related macular degeneration on the Eger macular stressometer photostress recovery time.

AIM: To assess the repeatability of Eger macular stressometer (EMS) measures of photostress recovery and determine their association with other measures of visual function. METHODS: EMS photostress recovery time was measured in 90 patients with bilateral exudative age related macular degeneration (AMD), 19 with bilateral atrophic AMD and 47 with both forms of the condition (mean age 79 (SD 13) years). Measurements were made on two occasions separated by 1 year. Intrasession repeatability was assessed by repeating the measures after a 10 minute recovery period at the first visit. Distance visual acuity was measured with a logMAR chart, near visual acuity with a MNRead chart at 25 cm, contrast sensitivity with a Pelli-Robson chart, and the presence of central visual disturbance assessed with an Amsler grid. A questionnaire was used to assess self reported difficulties with glare recovery. RESULTS: The average EMS recovery time was 11.0 (SD 8.9) seconds, decreasing by 1.6 (5.2) seconds on repeated measurement (p<0.05). EMS photostress recovery was not correlated with visual function measures or subjective difficulties with lights (p>0.05). EMS photostress recovery time did not predict those whose vision decreased over the following year compared with those among whom it remained stable. CONCLUSIONS: The EMS test is not a useful tool in determining the severity or progression of AMD.

Prevalence of reticular pseudodrusen in newly presenting adult onset foveomacular vitelliform dystrophy.

PurposeTo report the association and prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting adult onset foveomacular vitelliform dystrophy (AFVD). To compare the strength of association with other pathologies resulting from dysfunction of the choroid-Bruch's membrane-retinal pigment epithelium (RPE) complex, including eyes with geographic atrophy (GA) and angioid streaks.MethodsRetrospective single-centre review of all consecutive newly presenting AFVD. Multimodal imaging with spectral domain optical coherence tomography, fundus photographs, red-free/blue light images, and fundus fluorescein angiograms were graded for the presence of RPD. For comparison, all consecutive newly presenting cases of GA and eyes with angioid streaks were studied.ResultsFifteen (15) patients were identified with AFVD (mean age of 77.3 years; 73.3% female). Mean age of patients with AFVD and RPD was 80.5 years (SD 3.7), whereas that of patients with AFVD without RPD was 75.1 years (SD 7.0). This age difference did not reach statistical significance, P=0.1. Six (40%) had identifiable RPD; being a bilateral finding in 100% of patients. No males with AFVD and RPD were identified. A total of 92 eyes presented with GA. Twenty-three (23) of these (25.0%) had RPD. Twelve (12) patients presented with identifiable angioid streaks, with 4 (36.4%) having RPD.ConclusionRPD are a frequent finding in eyes with newly presenting AFVD; not being restricted to AMD, but a finding common among diseases where pathophysiological mechanisms involve damage to Bruch's membrane and the RPE, whether genetic or degenerative. Our study supports the concept that they occur with high but variable frequencies in eyes with various pathologies.

Verteporfin photodynamic therapy of choroidal neovascularization in angioid streaks: one-year results of a prospective case series.

PURPOSE: To report the 12-month results on the use of verteporfin photodynamic therapy (PDT) in the treatment of choroidal neovascularization (CNV) secondary to angioid streaks. STUDY DESIGN: Five-center prospective case series. METHODS: Patients with CNV secondary to angioid streaks who were treated with PDT were recruited and followed up at 3-month intervals for 12 months, with the addition of visits at 1.5 and 4.5 months if deemed appropriate by the investigator. Best-corrected visual acuity (BCVA) was measured at each visit after full refraction or with their current distance spectacles using Early Treatment Diabetic Retinopathy Study logarithm of the minimum angle of resolution charts. Stereoscopic fundus fluorescein angiography was used to determine baseline lesion characteristics and location. RESULTS: Twenty-two patients were recruited (23 eyes, 16 with subfoveal CNV and 7 with juxtafoveal; all classic no occult). Seventeen patients (77%) had angioid streaks secondary to pseudoxanthoma elasticum. In the subfoveal group, median BCVA at baseline was 49 letters (approximate Snellen equivalent, 20/100) and was 46 at 12 months (approximate Snellen equivalent, 20/125). Twelve of 16 eyes (75%) lost fewer than 8 letters, whereas 14 of 16 eyes (88%) lost fewer than 15 letters. The mean CNV greatest linear dimension (GLD) was 2520 microm at baseline. At 12 months, 7 of 16 eyes with subfoveal CNV at baseline were leaking (GLD = 3220 microm; P = 0.62). The mean number of treatments in the first 12 months was 2.9. In the juxtafoveal group, the median BCVA at baseline was 66 letters (approximate Snellen equivalent, 20/50) and was 51 letters at 12 months (approximate Snellen equivalent, 20/100). Two of 7 eyes (29%) gained 8 or more letters at the 12-month examination, whereas 4 of 7 eyes (57%) lost more than 15 letters. The mean CNV GLD at baseline was 1890 microm. At 12 months, 1 of 7 eyes with juxtafoveal CNV at baseline was leaking. Choroidal neovascularization progressed from juxtafoveal to subfoveal location during the follow-up period in 4 of 7 eyes. The mean number of treatments in the first 12 months was 3.4. No side effects were noted in either patient group. CONCLUSIONS: This small series suggests that treatment of CNV secondary to angioid streaks with verteporfin PDT seems to limit visual loss in most patients through the first 12 months of follow-up, particularly in those with subfoveal lesions at baseline.

Isolation, culture, and characterisation of human macular inner choroidal microvascular endothelial cells.

AIM: To develop a method for the reliable isolation of adult human macular inner choroidal endothelial cells (ICECs) and to subsequently characterise them for their expression of a range of endothelial cell associated surface markers. METHOD: Human ICECs were isolated after manual dissection of maculas from fresh human posterior segments. Following enzyme digestion to form a single cell suspension, the ICECs were isolated using anti-CD31 coated Dynabeads. The isolated cells were grown in culture and examined for typical endothelial cell morphology, surface expression of vWf, CD 31, CD 105, VEGF receptors 1 and 2, and expression of E-selectin after stimulation with TNF-alpha. The cells were also examined for their ability to form fenestrations and capillary-like tubes in Matrigel. RESULTS: The method enabled the rapid isolation of viable cells that demonstrated typical endothelial cobblestone morphology in culture. The cells stained positive for CD31, vWf, CD105, VEGF receptors 1 and 2, and E-selectin (after stimulation with TNF-alpha). The cells stained negative for alpha smooth muscle actin and fibroblast surface protein. The cells also developed fenestrations when cultured on fibronectin coated plates and formed capillary-like tubes structures when cultured on Matrigel. CONCLUSIONS: This technique isolates cells from the human macular inner choroid that display features consistent with vascular endothelial cells. These cells could subsequently be used to further the understanding of the pathophysiological mechanisms of diseases of the inner choroid, such as choroidal neovascularisation.

The efficacy of sirolimus in the treatment of patients with refractory uveitis.

AIMS: To determine the efficacy of sirolimus in the treatment of patients with severe non-infectious uveitis. METHODS: Eight patients with severe non-infectious uveitis were recruited to an open study. Inclusion criteria were limited to patients whose disease was not controlled with at least two or more separate steroid sparing immunosuppressants (either because of unacceptable side effects or ineffectiveness of the drug) or who required regular doses of corticosteroids either as high dose systemic or orbital floor injections in order to control their disease. Intraocular inflammation, visual acuity, symptoms, corticosteroid burden, drug toxicity, and side effects were monitored. RESULTS: Sirolimus therapy was effective in five of the eight patients, all of whom had their dose of corticosteroids reduced or discontinued. Treatment in three patients was considered a failure as it caused intolerable side effects and/or failed to control the uveitis. Side effects were common and were typically gastrointestinal or cutaneous in nature. The severity of symptoms was dose dependent in most cases and occurred at trough blood levels above 25 ng/ml. CONCLUSION: Sirolimus is an effective and potent immunosuppressive treatment in the majority of patients with non-infectious uveitis and can reduce the need for long term supplementary corticosteroid therapy. Further studies are required to establish the long term efficacy and safety of sirolimus alone or in combination with other steroid sparing immunosuppressants.

A review of therapies for diabetic macular oedema and rationale for combination therapy.

Diabetic macular oedema (DMO) is responsible for significant visual impairment in diabetic patients. The primary cause of DMO is fluid leakage resulting from increased vascular permeability through contributory anatomical and biochemical changes. These include endothelial cell (EC) death or dysfunction, pericyte loss or dysfunction, thickened basement membrane, loss or dysfunction of glial cells, and loss/change of EC Glycocalyx. The molecular changes include increased reactive oxygen species, pro-inflammatory changes: advanced glycation end products, intracellular adhesion molecule-1, Complement 5-9 deposition and cytokines, which result in increased paracellular permeability, tight junction disruption, and increased transcellular permeability. Laser photocoagulation has been the mainstay of treatment until recently when pharmacological treatments were introduced. The current treatments for DMO target reducing vascular leak in the macula once it has occurred, they do not attempt to treat the underlying pathology. These pharmacological treatments are aimed at antagonising vascular endothelial growth factor (VEGF) or non-VEGF inflammatory pathways, and include intravitreal injections of anti-VEGFs (ranibizumab, aflibercept or bevacizumab) or steroids (fluocinolone, dexamethasone or triamcinolone) as single therapies. The available evidence suggests that each individual treatment modality in DMO does not result in a completely dry macula in most cases. The ideal treatment for DMO should improve vision and improve morphological changes in the macular (eg, reduce macular oedema) for a significant duration, reduced adverse events, reduced treatment burden and costs, and be well tolerated by patients. This review evaluates the individual treatments available as monotherapies, and discusses the rationale and potential for combination therapy in DMO. A comprehensive review of clinical trials related to DMO and their outcomes was completed. Where phase III randomised control trials were available, these were referenced, if not available, phase II trials have been included.

Defining response to anti-VEGF therapies in neovascular AMD.

The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as 'responder status' after treatment for n-AMD, 'tachyphylaxis' and 'recalcitrant' n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when there is resolution of fluid (intraretinal fluid; IRF, subretinal fluid; SRF and retinal thickening), and/or improvement of >5 letters, subject to the ceiling effect of good starting VA. Poor response is defined as <25% reduction from the baseline in the central retinal thickness (CRT), with persistent or new IRF, SRF or minimal or change in VA (that is, change in VA of 0+4 letters). Non-response is defined as an increase in fluid (IRF, SRF and CRT), or increasing haemorrhage compared with the baseline and/or loss of >5 letters compared with the baseline or best corrected vision subsequently. Poor or non-response to anti-VEGF may be due to clinical factors including suboptimal dosing than that required by a particular patient, increased dosing intervals, treatment initiation when disease is already at an advanced or chronic stage), cellular mechanisms, lesion type, genetic variation and potential tachyphylaxis); non-clinical factors including poor access to clinics or delayed appointments may also result in poor treatment outcomes. In eyes classified as good responders, treatment should be continued with the same agent when disease activity is present or reactivation occurs following temporary dose holding. In eyes that show partial response, treatment may be continued, although re-evaluation with further imaging may be required to exclude confounding factors. Where there is persistent, unchanging accumulated fluid following three consecutive injections at monthly intervals, treatment may be withheld temporarily, but recommenced with the same or alternative anti-VEGF if the fluid subsequently increases (lesion considered active). Poor or non-response to anti-VEGF treatments requires re-evaluation of diagnosis and if necessary switch to alternative therapies including other anti-VEGF agents and/or with photodynamic therapy (PDT). Idiopathic polypoidal choroidopathy may require treatment with PDT monotherapy or combination with anti-VEGF. A committee comprised of retinal specialists with experience of managing patients with n-AMD similar to that which developed the Royal College of Ophthalmologists Guidelines to Ranibizumab was assembled. Individual aspects of the guidelines were proposed by the committee lead (WMA) based on relevant reference to published evidence base following a search of Medline and circulated to all committee members for discussion before approval or modification. Each draft was modified according to feedback from committee members until unanimous approval was obtained in the final draft. A system for categorising the range of responsiveness of n-AMD lesions to anti-VEGF therapy is proposed. The proposal is based primarily on morphological criteria but functional criteria have been included. Recommendations have been made on when to consider discontinuation of therapy either because of success or futility. These guidelines should help clinical decision-making and may prevent over and/or undertreatment with anti-VEGF therapy.

Choroidoretinal neovascularisation following radon seed treatment of retinoblastoma in two patients.

Two patients who developed localised radiation retinopathy many years after brachytherapy for retinoblastoma are described. In both patients extracapsular cataract extraction and YAG laser capsulotomy were followed by preretinal and vitreous haemorrhage and in one patient there was deterioration of existing radiation retinopathy with macular oedema. Premacular and vitreous haemorrhage occurred from focal, preretinal neovascular membranes which appeared to originate from residual choroidal vascular radicals. Laser photocoagulation was successful in ablating preretinal neovascular membranes and limiting the extent of macular oedema from incompetent retinal capillaries adjacent to the atrophic macular scars.

Reproducibility of volumetric measurements of normal maculae with the Heidelberg retina tomograph.

AIMS: The Heidelberg retina tomograph (HRT) is a scanning laser ophthalmoscope with confocal optics. The reproducibility of the optic nerve head topography is accurate and reliable. The authors describe a new technique for the assessment of macular thickening by volumetric quantification and present the results of its reproducibility in normal subjects. METHODS: Topographic images of the macula, centred on the fovea were obtained in one eye of 44 normal subjects. The volumes above the reference plane bound by a 1 mm, 2 mm, and 3 mm diameter circle were measured. The reference plane was adjusted to the lowest point of the height variation of the contour line at each examination. The reproducibility of repeated measurements within a 2 mm diameter circle was assessed in 20 eyes selected at random. Three HRT scans of each eye were obtained. The measurements of volume above reference plane of each scan were repeated three times on three separate days. RESULTS: The intrascan coefficients of variability measured 7.12-9.57%. The 95% confidence interval for the geometric mean ratio of single volume measurements was 0.92 to 1.24 for scans 1 and 2, 0.89 to 1.17 for scans 1 and 3, and 0.81 to 1.12 for scans 2 and 3. When the mean of three measurements of one scan were compared with the mean of three measurements of a second scan, the 95% confidence interval for their geometric mean ratio was 0.89 to 1.20 for scans 1 and 2, 0.89 to 1.16 for scans 1 and 3, and 0.84 to 1.13 for scans 2 and 3. The average standard deviation (SD) for one measurement per scan was 0.02 mm3, and 0.019 mm3 for two or three measurements per scan. Linear regression demonstrated a significant increase in SD as volumetric measurements increased (p = 0.003). Age did not significantly affect the SD of volumetric measurements (p = 0.797). The authors found no significant differences in volumetric measurements across all ages for all three circles (p = 0.314, p = 0.471, p = 0.267). CONCLUSION: Good reproducibility for volumetric measurements at the macula was found with the HRT using the above technique in normal subjects. This method may be extremely useful for the identification and quantification of diabetic macular oedema and for monitoring the effects of argon laser photocoagulation.

The combined effect of diabetes and ionising radiation on the retinal vasculature of the rat.

The clinical impression that pre-existing diabetes exacerbates radiation injury to the retinal vasculature was studied in STZ diabetic rats. Half of 2 groups of streptozotocin (STZ)-induced diabetic rats and 1 group of normal animals had their right eyes irradiated with 1000 cGy of 90 KVP x-rays. The prevalence of acellular capillaries in trypsin digests of the retinal vasculature was quantified for each of the 6 groups of animals at 6.5 months post-irradiation. The prevalence of acellular capillaries in both non-irradiated diabetic groups was significantly higher than in controls while the irradiated animals in each of the three main categories showed a statistically significant increase compared to their non-irradiated equivalents. However, the net increase in acellular capillaries following irradiation was much greater in rats with an 8 month term of pre-existing diabetes (180%) than in those which had only been diabetic for 3 months (36%). The results of this study suggest a synergistic relationship between pre-existing diabetes and ionising radiation in the development of retinal vasculopathy, and that the potentiation of the vascular damage is dependent on the duration of diabetes prior to radiation exposure.

The visual results and changes in retinopathy in diabetic patients following cataract surgery.

INTRODUCTION: A study was designed to investigate the visual improvement and incidence of progression of retinopathy in diabetic patients following extracapsular cataract extraction or phacoemulsification. They were compared to a matched group of non-diabetic patients. METHODS: A retrospective analysis of all diabetic patients (118) undergoing ECCE (90) or phacoemulsification (28) in 1995. These patients were operation and age matched with 118 non-diabetic patients who underwent surgery during the same year. RESULTS: There was no statistically significant difference in complications following ECCE in diabetic and non-diabetic patients (p = 0.2). Complications were however more common in non-diabetic patients undergoing phacoemulsification compared to diabetics undergoing the same procedure (p = 0.046). Although consultants performed 42% of the surgery in diabetics compared to 31% in non-diabetics, there was no significant difference in the rate of complications between consultants and residents (p = 0.8). Overall the visual improvement in non-diabetics was better than diabetic patients (p = 0.006). This was due to a better improvement amongst non-diabetic patients undergoing phacoemulsification (p = 0.02). Overall, cataract surgery was found to lead to a worsening in retinopathy in 19 operated eyes (15 had no retinopathy preoperatively) compared to a worsening in 8 fellow eyes. This was statistically significant (p = 0.04). However, ECCE was no more likely to cause worsening of retinopathy than phacoemulsification (p = 0.87). CONCLUSIONS: Diabetic patients due to undergo cataract surgery a) have a good chance of visual improvement but to a level less than if they were not diabetic, b) have a greater chance of visual loss, c) surgery may initiate or worsen any pre-existing retinopathy and this may affect their vision in the future.

Indocyanine green angiography versus fluorescein angiography in the follow-up of choroidal melanomas treated with RU106/RH106.

Indocyanine-green angiography and fluorescein angiography may complement each other in the follow-up and evaluation of choroidal melanomas treated with brachytherapy and may give a better understanding in the process of response of choroidal melanomas to brachytherapie. We did a retrospective study on 18 patients treated for this pathology.

Quality of bevacizumab compounded for intravitreal administration.

AIM: To compare the quality and stability of unlicensed, repackaged bevacizumab intended for intravitreal injection, as provided by five licensed compounding pharmacies in the United Kingdom, with bevacizumab in its original glass vial. METHODS: Repackaged bevacizumab was obtained from five UK suppliers. Samples were analyzed at two time points (day 1 and day 14). Microflow imaging was performed to evaluate subvisible particle size, particle density, and particle size distribution. Protein concentration, immunoglobulin G (IgG) content, and molecular weight were also determined. RESULTS: A significant difference in subvisible particle density was observed between bevacizumab batches from the five suppliers on day 1 (P<0.001). An increase in subvisible particle density was observed between day 1 and 14 for repackaged bevacizumab from all suppliers (all P<0.05), but not the reference compound. Protein concentration, IgG content, and molecular weight were comparable between batches from each supplier and the reference bevacizumab. DISCUSSION: The study results indicate that the quality of bevacizumab repackaged into prefilled plastic syringes is variable among the different compounding pharmacies in the United Kingdom. Furthermore, particle density may increase with storage in repackaged syringes. It is noteworthy that particle size distribution in both the repackaged and reference bevacizumab fell outside of the range specified by the United States Pharmacopeia for injectable ophthalmic solutions. These data highlight the need for further research into the use of unlicensed, repackaged bevacizumab intended for intravitreal injection.

Intravitreal ranibizumab for the treatment of choroidal neovascularisation secondary to angioid streaks.

AIMS: To assess the medium to long-term efficacy and safety of intravitreal ranibizumab for the treatment of choroidal neovascularisation (CNV) secondary to angioid streaks (AS). METHODS: A total of 12 eyes of nine patients treated with intravitreal ranibizumab (0.5 mg in 0.05 ml) for CNV secondary to AS were retrospectively identified. Efficacy of treatment was determined by changes in best-corrected LogMAR visual acuity (BCVA) and optical coherence tomography. Changes with respect to baseline BCVA were defined as improved or reduced with a gain or loss of more than 10 letters, respectively, or stable if remaining within 10 letters. RESULTS: Over a mean follow-up of 21.75 months (range: 1-54), patients received mean 5.75 (range: 2-15) intravitreal ranibizumab injections per affected eye. BCVA improved in three eyes (25%), stabilised in eight eyes (66.67%), and deteriorated in one eye (8.33%). There was no significant change in central retinal thickness (CRT) over the follow-up period (P=0.1072). No drug-related systemic side effects were recorded. CONCLUSION: The long-term treatment of CNV secondary to AS with intravitreal ranibizumab showed a stabilisation in CRT and an improvement or stabilisation of BCVA. The absence of systemic side effects was reassuring. Further long-term prospective studies are required to validate these findings.

Central retinal artery occlusion following peribulbar anesthesia for pterygium excision.

Pterygium is a common ocular surface pathology in tropical environments. In the early stages, it may be managed medically with topical anti-inflammatory agents and ocular lubricants. However as the disease progresses, surgical excision becomes necessary and several anaesthetic methods may be used to assist this. We share our experience of a 30-year old woman who underwent uneventful pterygium excision using peribulbar lignocain injection with adrenaline. She developed sudden blindness due to central retinal artery occlusion with macular infarction. While peribulbar anaesthesia is generally safe, a remote risk of retinal vascular accident exists and its routine use should be done with caution. Where possible topical anaesthesia with or without intra-lesional injection be employed.