Catey Bunce

A Prospective Randomized Trial of Intravitreal Bevacizumab or Laser Therapy in the Management of Diabetic Macular Edema (BOLT Study): 12-Month Data: Report 2

PURPOSE To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant diabetic macular edema (CSME). DESIGN Prospective, randomized, masked, single-center, 2-year, 2-arm clinical trial. PARTICIPANTS A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT. METHODS Subjects were randomized to either ivB (6 weekly; minimum of 3 injections and maximum of 9 injections in the first 12 months) or MLT (4 monthly; minimum of 1 treatment and maximum of 4 treatments in the first 12 months). MAIN OUTCOME MEASURES The primary end point was the difference in ETDRS best-corrected visual acuity (BCVA) at 12 months between the bevacizumab and laser arms. RESULTS The baseline mean ETDRS BCVA was 55.7+/-9.7 (range 34-69) in the bevacizumab group and 54.6+/-8.6 (range 36-68) in the laser arm. The mean ETDRS BCVA at 12 months was 61.3+/-10.4 (range 34-79) in the bevacizumab group and 50.0+/-16.6 (range 8-76) in the laser arm (P = 0.0006). Furthermore, the bevacizumab group gained a median of 8 ETDRS letters, whereas the laser group lost a median of 0.5 ETDRS letters (P = 0.0002). The odds of gaining > or =10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group (adjusted odds ratio, 5.1; 95% confidence interval, 1.3-19.7; P = 0.019). At 12 months, central macular thickness decreased from 507+/-145 microm (range 281-900 microm) at baseline to 378+/-134 microm (range 167-699 microm) (P<0.001) in the ivB group, whereas it decreased to a lesser extent in the laser group, from 481+/-121 microm (range 279-844 microm) to 413+/-135 microm (range 170-708 microm) (P = 0.02). The median number of injections was 9 (interquartile range [IQR] 8-9) in the ivB group, and the median number of laser treatments was 3 (IQR 2-4) in the MLT group. CONCLUSIONS The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia.

Leading causes of certification for blindness and partial sight in England & Wales

BackgroundPrevention of visual impairment is an international priority agreed at the World Health Assembly of 2002- yet many countries lack contemporary data about incidence and causes from which priorities for prevention, treatment and management can be identified.MethodsRegistration as blind or partially-sighted in England and Wales is voluntary and is initiated by certification by a consultant ophthalmologist. From all certificates completed during the year April 1999 to March 2000, the main cause of visual loss was ascertained where possible and here we present information on the leading causes observed and comment on changes in the three leading causes since the last analysis conducted for 1990–1991 data.Results13788 people were certified as blind, 19107 were certified as partially sighted. The majority of certifications were in the older age groups. The most commonly recorded main cause of certifications for both blindness (57.2 %) and partial sight (56 %) was degeneration of the macula and posterior pole which largely comprises age-related macular degeneration. Glaucoma and diabetic retinopathy were the next most commonly recorded main causes. Overall, the age specific incidence of all three leading causes has increased since 1990–1991 – with changes in diabetic retinopathy being the most marked – particularly in the over 65s where figures have more than doubled.ConclusionThe numbers of individuals per 100,000 population being certified blind or partially sighted due to the three leading causes – AMD, diabetic retinopathy and glaucoma have increased since 1990. This may to some extent be explained by improved ascertainment. The process of registration for severe visual impairment in England and Wales is currently undergoing review. Efforts must be made to ensure that routine collection of data on causes of severe visual impairment is continued, particularly in this age of improved technology, to allow such trends to be monitored and changes in policy to be informed.

Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy : Results from a randomized, double-blind, controlled clinical trial.

PURPOSE To assess the safety and efficacy of adjuvant combination therapy using 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) for prevention of proliferative vitreoretinopathy (PVR) after vitrectomy and retinal reattachment surgery. DESIGN Prospective randomized, double-masked, placebo controlled trial. PARTICIPANTS One hundred seventy-four high-risk patients were randomized to receive either 5-FU and LMWH therapy or placebo. Patients were selected from all patients undergoing primary vitrectomy for rhegmatogenous retinal detachment. METHOD Results of standard surgery with 5-FU and LMWH therapy or placebo were compared at the 6-month follow-up. MAIN OUTCOME MEASURES Development of postoperative PVR, retinal reattachment at 6 months after surgery, single operation reattachment rate, number of reoperations, and best-corrected visual acuity. RESULTS There were 87 patients in the 5-FU and LMWH therapy group and 87 in the placebo group. The incidence of postoperative PVR was significantly lower (P = 0.02) in the 5-FU and LMWH therapy compared with the placebo group. In 26.4% (23/87) of the placebo group and in 12.6% (11/87) of the 5-FU and LMWH group, postoperative PVR developed. In the 5-FU and LMWH group, the number of patients undergoing more than one operation was 19.5% (17/87) and the number of reoperations resulting from PVR was 52.9% (9/17). In the placebo group, the number of patients undergoing more than one operation was 25.3% (22/87) and the number of reoperations resulting from PVR was 72.7% (16/22). The difference in visual acuity was not statistically different in the two treatment groups, although those patients in whom postoperative PVR developed tended to have poorer vision (P < 0.0001). There were no differences in complication rates between the two groups. CONCLUSIONS There is a significant reduction in the incidence of postoperative PVR in patients receiving the 5-FU and LMWH therapy and in the reoperation rate resulting from PVR. This trial shows that incidence of PVR can be reduced with inexpensive and simple pharmacologic treatment with 5-FU and LMWH and should be used routinely in the treatment of patients at risk of developing PVR.

Cystic bleb formation and related complications in limbus- versus fornix-based conjunctival flaps in pediatric and young adult trabeculectomy with mitomycin C.

OBJECTIVE Comparison of fornix- and limbus-based conjunctival flaps with respect to cystic bleb-related complications of trabeculectomy with high-dose mitomycin C (MMC) in pediatric and young adult glaucoma. DESIGN Retrospective nonrandomized comparative interventional case series. PARTICIPANTS Thirty-seven patients. METHODS Identification of patients aged <30 years from operating theater records from 1995 and 1996 of the Moorfields Pediatric Glaucoma Service who had trabeculectomy with an MMC concentration of >/=0.4 mg/ml. Over a 2-year period, 37 consecutive operations matching these criteria were performed by a single surgeon: 20 with a limbus-based flap and 17 with a fornix-based flap. Except for the conjunctival incision and associated alteration in antimetabolite application and wound closure, the surgical technique was not significantly different between the groups. MAIN OUTCOME MEASURES Bleb evolution and complications. RESULTS The age at time of surgery, MMC concentration, history of one or more previous surgeries, and follow-up were similar in the 2 groups. The risk of cystic bleb formation was greater in the limbus-based flap group (90% in the limbus-based group vs. 29% in the fornix-based group; P<0.001). Late hypotony and bleb-related ocular infection were more common in the limbus-based flap group (P<0.05) and occurred earlier. There were four episodes of bleb-related infection (20%) in the limbus-based group (three of these [15%] were bleb-related endophthalmitis) and none in the fornix-based group. CONCLUSIONS In pediatric and young adult trabeculectomy with high doses of MMC, limbus-based flaps may be more likely to develop serious bleb-related complications and may develop these earlier than fornix-based flaps. The higher rates of complications could be attributable to the differences in bleb morphology, with limbus-based flap cases more likely to develop cystic blebs.

Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival

BACKGROUND The histological characteristics of ocular adnexal lymphomas have previously provided only a limited guide to clinical outcome for affected patients. This clinicopathological relation was re-examined using the Revised European American Lymphoma (REAL) system to classify the tumours in a large cohort of patients. METHODS The biopsies and clinical follow up data for 192 patients with ocular adnexal lymphoma were reviewed, the biopsies being regraded in accordance with the REAL classification. For each of five histological groups, logistic regression analysis was used to determine the odds ratios (OR) for the presence of systemic disease at the time of orbital diagnosis and Cox regression analysis was used to assess the hazard ratios (HR) for disseminated disease and lymphoma related death. For 108 patients in whom extraorbital spread occurred, the histological category of lymphoma was compared with the sites of dissemination. RESULTS At presentation, the frequency of previous or concurrent extraorbital disease increased from marginal zone lymphoma (OR 1.0), diffuse lymphoplasmacytic/lymphoplasmacytoid lymphoma (OR 2.3), follicle centre lymphoma (OR 3.8), diffuse large B cell lymphoma (OR 4.0) to other histological lymphoma variants (OR 26.8). For all histological types, the estimated risk of extraorbital disease and lymphoma related death continued for many years and the proportion of patients with at least one extraorbital recurrence after 5 years was 47% for MZL, 48% for LPL, 64% for FCL, 81% for DLCL, and 95% for other lymphoma variants. The corresponding estimated rates for 5 year lymphoma related mortality were 12%, 19%, 22%, 48%, and 53% respectively. CONCLUSIONS Patients with ocular adnexal lymphoma can be classified by REAL into five distinct groups, which show a progressive increase in the risks of extraorbital disease at diagnosis, of disease dissemination with time, and of tumour related death.

Frequency of asymmetric visual field defects in normal-tension and high-tension glaucoma

OBJECTIVE The purpose of the study was to evaluate the frequency of asymmetric visual field loss at presentation in patients with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG). DESIGN A retrospective cross-sectional study design was used. PARTICIPANTS Four hundred and three NTG patients and 337 consecutive HTG patients (consecutive diagnoses between 1986 and 1996). INTERVENTION Analysis of the frequency of unilateral field loss presentations in NTG and HTG. The visual fields of fellow eyes were compared to determine the side of more severe field loss. For the NTG patients, the relationship between the side with greater field loss and corresponding intraocular pressure (IOP) was investigated. MAIN OUTCOME MEASURES Humphrey field analyzer mean defect (MD) and mean diurnal IOP. RESULTS In the NTG group, 101 (25%) patients presented with unilateral field loss. The proportion of cases with unilateral field loss decreased with increasing age of presentation (chi-square test for trend = 26.9; P < 0.0001). Sixty-four percent of the patients had unilateral field loss in the left eye. Sixty-eight percent of the cases with bilateral field loss had a higher MD in the left eye. The diurnal IOP was estimated as 0.23 +/- 0.068 mmHg (mean +/- SE) higher in the left eye (P = 0.001). In the HTG group, 104 (31%) patients presented with unilateral field loss. The proportion of cases with unilateral field loss decreased with increasing age of presentation (chi-square test for trend = 4.6; P = 0.03). Right and left eyes had an equal chance of having field loss in unilateral cases and of being the side of more advanced field damage in bilateral cases. CONCLUSIONS The frequency of cases with unilateral field loss was similar in HTG and NTG patients. Patients with unilateral field loss at presentation were more likely to be at the younger end of the age range. In the NTG population we studied, the left eye was more frequently the side of onset of field loss and 2.1 times more likely to present with a greater field defect than the right eye. In HTG patients, right and left eyes showed an equal chance of being the side of onset of field damage and the more affected side.

A comparison of four methods of tonometry: method agreement and interobserver variability

Aim: To compare the inter-method agreement in intraocular pressure (IOP) measurements made with four different tonometric methods. Methods: IOP was measured with the Goldmann applanation tonometer (GAT), Tono-Pen XL, ocular blood flow tonograph (OBF), and Canon TX-10 non-contact tonometer (NCT) in a randomised order in one eye of each of 105 patients with ocular hypertension or glaucoma. Three measurements were made with each method, and by each of two independent GAT observers. GAT interobserver and tonometer inter-method agreement was assessed by the Bland-Altman method. The outcome measures were 95% limits of agreement for IOP measurements between GAT observers and between tonometric methods, and 95% confidence intervals for intra-session repeated measurements. Results: The mean differences (bias) in IOP measurements were 0.4 mm Hg between GAT observers, and 0.6 mm Hg, 0.1 mm Hg, and 0.7 mm Hg between GAT and Tono-Pen, OBF, and NCT, respectively. The 95% limits of agreement were smallest (bias ±2.6 mm Hg) between GAT observers, and larger for agreement between the GAT and the Tono-Pen, OBF, and NCT (bias ±6.7, ±5.5, and ±4.8 mm Hg, respectively). The OBF and NCT significantly underestimated GAT measurements at lower IOP and overestimated these at higher IOP. The repeatability coefficients for intra-session repeated measurement for each method were ±2.2 mm Hg and ±2.5 mm Hg for the GAT, ±4.3 mm Hg for the Tono-Pen, ±3.7 mm Hg for the OBF, and ±3.2 mm Hg for the NCT. Conclusions: There was good interobserver agreement with the GAT and moderate agreement between the NCT and GAT. The differences between the GAT and OBF and between the GAT and Tono-Pen probably preclude the OBF and Tono-Pen from routine clinical use as objective methods to measure IOP in normal adult eyes.

Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study.

Objectives To evaluate the efficacy and safety of intravitreous bevacizumab injections for the treatment of neovascular age related macular degeneration. Design Prospective, double masked, multicentre, randomised controlled trial. Setting Three ophthalmology centres in the United Kingdom. Participants 131 patients (mean age 81) with wet age related macular degeneration randomised 1:1 to intervention or control. Interventions Intravitreous bevacizumab (1.25 mg, three loading injections at six week intervals followed by further treatment if required at six week intervals) or standard treatment available at the start of the trial (photodynamic treatment with verteporfin for predominantly classic type neovascular age related macular degeneration, or intravitreal pegaptanib or sham treatment for occult or minimally classic type neovascular age related macular degeneration). Main outcome measures Primary outcome: proportion of patients gaining ≥15 letters of visual acuity at one year (54 weeks). Secondary outcomes: proportion of patients with stable vision and mean change in visual acuity. Results Of the 131 patients enrolled in the trial, five patients did not complete the study because of adverse events, loss to follow-up, or death. In the bevacizumab group, 21 (32%) patients gained 15 or more letters from baseline visual acuity compared with two (3%) in the standard care group (P<0.001); the estimated adjusted odds ratio was 18.1 (95% confidence interval 3.6 to 91.2) and the number needed to treat was 4 (3 to 6). In addition, the proportion of patients who lost fewer than 15 letters of visual acuity from baseline was significantly greater among those receiving bevacizumab treatment (91% (59) v 67% (44) in standard care group; P<0.001). Mean visual acuity increased by 7.0 letters in the bevacizumab group with a median of seven injections compared with a decrease of 9.4 letters in the standard care group (P<0.001), and the initial improvement at week 18 (plus 6.6 letters) was sustained to week 54. Among 65 patients treated with bevacizumab, there were no cases of endophthalmitis or serious uveitis related to the intervention. All end points with respect to visual acuity in the study eye at 54 weeks favoured bevacizumab treatment over standard care. Conclusions Bevacizumab 1.25 mg intavitreous injections given as part of a six weekly variable retreatment regimen is superior to standard care (pegaptanib sodium, verteporfin, sham), with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 54 weeks. Trial registration number Current controlled trials ISRCTN83325075

A comparison of the causes of blindness certifications in England and Wales in working age adults (16–64 years), 1999–2000 with 2009–2010

Objectives To report on the causes of blindness certifications in England and Wales in working age adults (16–64 years) in 2009–2010; and to compare these with figures from 1999 to 2000. Design Analysis of the national database of blindness certificates of vision impairment (CVIs) received by the Certifications Office. Setting and participants Working age (16–64 years) population of England and Wales. Main outcome measures Number and cause of blindness certifications. Results The Certifications Office received 1756 CVIs for blindness from persons aged between 16 and 64 inclusive between 1 April 2009 and 31 March 2010. The main causes of blindness certifications were hereditary retinal disorders (354 certifications comprising 20.2% of the total), diabetic retinopathy/maculopathy (253 persons, 14.4%) and optic atrophy (248 persons, 14.1%). Together, these three leading causes accounted for almost 50% of all blindness certifications. Between 1 April 1999 and 31 March 2000, the leading causes of blindness certification were diabetic retinopathy/maculopathy (17.7%), hereditary retinal disorders (15.8%) and optic atrophy (10.1%). Conclusions For the first time in at least five decades, diabetic retinopathy/maculopathy is no longer the leading cause of certifiable blindness among working age adults in England and Wales, having been overtaken by inherited retinal disorders. This change may be related to factors including the introduction of nationwide diabetic retinopathy screening programmes in England and Wales and improved glycaemic control. Inherited retinal disease, now representing the commonest cause of certification in the working age population, has clinical and research implications, including with respect to the provision of care/resources in the NHS and the allocation of research funding.

Detection of optic disc change with the Heidelberg retina tomograph before confirmed visual field change in ocular hypertensives converting to early glaucoma

AIM To determine whether analysis of sequential optic disc images obtained with the Heidelberg retina tomograph (HRT) is able to demonstrate optic disc change before the development of reproducible field defects in a group of ocular hypertensive (OHT) patients converting to early glaucoma. METHODS Two groups were analysed: (1) 13 eyes of 13 OHT patients who subsequently developed reproducible field defects (converters); and (2) 13 eyes of 11 normal control subjects. Two sequential optic disc images were obtained using the HRT (median separation between images was 12 months for the converters and 13 months for the normals). The second image in the converter group was obtained before confirmed visual field loss. The optic disc variables were analysed both globally and segmentally using HRT software version 1.11. The Wilcoxon signed rank test was used to determine if there were any significant differences between the variables of the two image sets. RESULTS Significant optic disc change was demonstrated in the group of converters: (1) global variables: the cup area increased by 9.7%, the C/D area ratio increased by 10.5%, and the rim area decreased by 6.9%; (2) segmental variables: the superonasal cup area increased by 11.0%, the superonasal C/D area ratio increased 11.7%, and the inferonasal cup volume increased by 28.4%.The temporal rim volume decreased by 15.6%, the inferotemporal rim volume decreased by 23.6%, and the rim area in the superonasal and superotemporal segments decreased by 6.6% and 6.9% respectively. CONCLUSION Analysis of sequential optic disc images on the HRT allowed the detection of glaucomatous change before confirmed visual field change in a group of OHT patients converting to early glaucoma.