Macular Degeneration: Bunce C

Sivaprasad S, Bunce C, Wormald R. · Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK. · Br J Ophthalmol. · Pubmed #16234444 links to  free full text

Abstract: AIM: To examine the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of cystoid macular oedema (CMO) following cataract surgery. METHODS: Systematic literature review of randomised controlled trials (RCTs) that evaluated the effects of NSAIDs in the treatment of CMO following cataract surgery was done according to the Cochrane Collaboration methodology. RESULTS: Seven trials involving a total of 266 participants were included. Four trials studied the effects of NSAIDs in chronic CMO while the other three trials examined the effect of NSAIDs in acute CMO. Little evidence of effectiveness was found for oral indomethacin and topical fenoprofen for chronic CMO in two small trials. Treatment with topical 0.5% ketorolac for chronic CMO was found to be effective in two trials. Three trials examined the effect of topical NSAIDs on acute CMO. The comparisons among these studies were of a NSAID to placebo, prednisolone or another NSAID. Because of considerable heterogeneity between these study designs, their results were not combined in a meta-analysis. CONCLUSION: A positive effect of topical NSAID (0.5% ketorolac tromethamine ophthalmic solution) on chronic CMO was noted. However, there is not enough evidence to show the effectiveness of NSAIDs in acute CMO following cataract surgery.

Sivaprasad S, Bunce C, Patel N. · West Kent Eye Centre, Farnborough Hospital, Orpington, UK, BR6 8ND. · Cochrane Database Syst Rev. · Pubmed #15674935 No free full text.

Abstract: BACKGROUND: Cystoid macular oedema (CMO) is the accumulation of fluid in the central retina (the macula) due to leakage from dilated capillaries. It is the most common cause of poor visual outcome following cataract surgery. The exact cause is unclear. Acute CMO, defined as oedema of less than four months duration, often resolve spontaneously. CMO that persists for four months or more is termed chronic CMO. Different types of non-steroidal anti-inflammatory agents (NSAIDs) are used in the treatment of CMO which may be delivered topically or systemically. OBJECTIVES: To examine the effectiveness of NSAIDs in the treatment of CMO following cataract surgery. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 2 2004), MEDLINE (1966 to April 2004), EMBASE (1980 to May 2004), LILACS (April 2004) and the reference lists of identified trials. We searched conference abstracts (sessions related to cataract) in ARVO 1975 to 2003. We contacted experts in the field and NSAIDs manufacturers for details on published and unpublished trials. SELECTION CRITERIA: Randomised controlled trials evaluating the effects of NSAIDs in the treatment of CMO following cataract surgery. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data. Since considerable heterogeneity was observed between studies we did not conduct meta-analyses. MAIN RESULTS: Seven trials involving a total of 266 participants were included. Four trials studied the effects of NSAIDs in chronic CMO while the other three examined the effect of NSAIDs in acute CMO. Of the studies examining chronic CMO, one study enrolled 120 participants, but the remainder had 34 or fewer participants. Four different NSAIDs were used and administered in different ways. Indomethacin was used orally and was found to be ineffective for chronic CMO in one trial. Topical fenoprofen was also found to be ineffective for chronic CMO in another small trial. Treatment with topical 0.5% ketorolac for chronic CMO was found to be effective in two trials.Three trials examined the effect of topical NSAIDs on acute CMO. The comparisons among these studies were of an NSAID to placebo, prednisolone or another NSAID. The study design differed between the studies in other important aspects thus they could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS: This review found two trials which showed that topical NSAID (0.5% ketorolac tromethamine ophthalmic solution) has a positive effect on chronic CMO. However, the effects of NSAIDs in acute CMO remains unclear and needs further investigation.

Thomas D, Bunce C, Moorman C, Laidlaw DA. · Department of Ophthalmology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK. · Br J Ophthalmol. · Pubmed #15615752 links to  free full text

Abstract: AIM: (1) To evaluate whether vitrectomy is preferable to further macular laser in improving visual acuity and resolving retinal thickening in patients with diabetic macular oedema (DMO) despite previous laser and no macular traction. (2) To determine the feasibility of further trials in this population in terms of magnitude of comparative clinical effect, rate of recruitment, and loss to follow up. METHODS: A randomised controlled feasibility study. Patients with DMO and a visual acuity of 0.3 logMAR (6/12) or worse after one or more macular laser treatments were randomised on a 1:1 basis to either pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling or further macular laser. Patients with a posterior vitreous detachment, biomicroscopic evidence of retinal traction, or a taut thickened posterior hyaloid (TTPH) were excluded. Primary outcome measures were (1) best corrected logMAR visual acuity, (2) mean central macular thickness on optical coherence tomography, and (3) rate of recruitment and loss to follow up. Analysis was on an intention to treat basis. RESULTS: 19 patients were randomised to PPV and 21 to further macular laser. The mean baseline logMAR visual acuity was 0.65 (SD 0.28) for the group randomised to PPV and 0.60 (0.23) for the group randomised to laser. The mean change in best corrected visual acuity of the vitrectomy group was deterioration by 0.05 logMAR, while in the control group the mean change was an improvement of 0.03 logMAR. The median (interquartile range) baseline central macular thickness was 403 (337, 492) for the group randomised to PPV and 387 (298, 491) for the controls randomised to laser. The median change in central macular thickness from baseline to review in the vitrectomy group was a thinning by 73 mum (20%) and by 29 mum (10.7%) in the control laser group. This single centre was able to recruit 40 patients in 18 months with follow up of 82% at 1 year. CONCLUSION: A randomised controlled trial was found to be potentially feasible in this population, the rate of recruitment was however slow and one in five patients were lost to follow up because of death and ill health. These data provide little evidence in terms of visual acuity and macular thickness of any benefit of vitrectomy over further macular laser in patients with an attached hyaloid, DMO despite previous laser, and no clinically evident macular traction or TTPH.

Owens SL, Bunce C, Brannon AJ, Wormald R, Bird AC, Anonymous00270. · Medical Retinal Service, Moorfields Eye Hospital, London, UK. · Eye. · Pubmed #12855972 No free full text.

Abstract: PURPOSE: The Drusen Laser Study (DLS) of high-risk age-related maculopathy (ARM) is a randomised, controlled clinical trial designed to answer two questions: (1). Do drusen resolve after macular laser photocoagulation (2). Does macular laser photocoagulation prevent choroidal neovascularisation (CNV) in high-risk eyes? In this report, we present the results of the interim, pooled analysis of CNV prophylaxis for patients in the Unilateral Group of the DLS. METHODS: The DLS is a randomised controlled clinical trial of prophylactic macular photocoagulation for high-risk ARM. Patients in the Unilateral Group had a neovascular complication in the first eye; their fellow eye (Study Eye) had visual acuity of 6/12 or better and drusen. Following informed consent, patients were randomised to the Treatment Group or the No Treatment Group. Patients randomised to treatment received 12 light spots of argon laser photocoagulation to their Study Eye: four burns were placed 750 microm from the centre of the fovea at 12, 3, 6, and 9 o'clock, and the eight remaining burns were placed 1500 microm from the centre of the fovea at 12, 1:30, 3, 4:30, 6, 7:30, 9, and 10:30 o'clock. Drusen were treated directly only if they were present at the protocol treatment locations. All patients were followed in an identical fashion at regular intervals. Best-corrected visual acuity was measured and recorded by a masked observer. Fluorescein angiography was performed at baseline and yearly review, as well as nonprotocol visits if symptoms suggested CNV. Five clinical centres utilised and conformed to a common DLS protocol. Patient care and data collection methodologies were deemed sufficiently similar to permit a pooled data analysis. RESULTS: There were 156 patients included in the interim analysis, and timed information was available on 153. CNV occurred in 21 of 81 (26%) patients in the Treatment Group and in 13 of 75 (17%) patients in the No Treatment Group (P=0.19). Kaplan-Meier survival analysis showed earlier onset of CNV in the Treatment Group compared to patients in the No Treatment Group (statistical significance not calculated). Visual acuity loss at 2 years occurred in nine of 54 (17%) patients in the Treatment Group compared to the two of 48 (4%) patients in the No Treatment Group (P=0.056). CONCLUSIONS: We are only the second group to identify possible laser-induced CNV despite other similar studies in progress. Equipoise of the DLS investigators was lost, and recruitment was halted. We feel ethically bound to notify the ophthalmic community of this finding.

Sallo FB, Peto T, Leung I, Xing W, Bunce C, Bird AC. · Department of Research and Development, Moorfields Eye Hospital, London, United Kingdom. · Curr Eye Res. · Pubmed #19274532 No free full text.

Abstract: PURPOSE: To determine whether grading based on the International Classification (IC) for age-related macular degeneration (AMD) allows recognition of change during the progression of the disease. METHODS: Stereoscopic color fundus photographs of 50 eyes of 25 patients with AMD and at least 5 years of review were graded in a random and masked fashion for changes over time in the characteristics of drusen, pigmentary changes, and end-stage disease, according to the system defined by the IC for AMD, by two independent graders (F.B.S., I.L.). Fundus images were also analyzed in time sequence for clinical changes by a senior grader (I.L.) and two ophthalmologists (A.C.B., T.P.) without access to the grading forms of the IC grading. Clinical change, as recorded by the IC grading and the individual analysis, were compared. RESULTS: There was 97.8% (kappa = 0.70) concordance in identification of change. In four cases, the clinical classification differed from the IC grading: Two cases of drusen and two of end-stage disease grading. Inter-observer agreement for the IC grading was 89.4% for predominant phenotype (kappa = 0.84), 89.36-91.49% for presence of choroidal neovascularization (CNV) (kappa = 0.79-0.83), 87.23-89.36% for geographic atrophy (GA) (kappa = 0.62-0.74) and 55.32% for area covered by drusen (kappa = 0.31). CONCLUSIONS: Overall, progression from earlier stages of AMD to either of the two forms of advanced AMD were reflected accurately by the IC grading in the vast majority of cases.

Barsam A, Chandra A, Bunce C, Whitefield LA. · Moorfields Eye Hospital, London, United Kingdom. · J Cataract Refract Surg. · Pubmed #18499007 No free full text.

Abstract: PURPOSE: To compare the effect of ultrasound (US) phacoemulsification and AquaLase liquefaction (Alcon Laboratories) cataract surgery on the macula using optical coherence tomography (OCT). SETTING: Department of Ophthalmology, Queen Mary's Hospital, London, United Kingdom. METHODS: Sixty-three patients having cataract surgery were randomized to receive US phacoemulsification or AquaLase liquefaction cataract surgery. Macular thickness and volume were evaluated by OCT preoperatively and 2 and 6 weeks postoperatively. The primary outcomes were OCT central macular thickness and best corrected visual acuity at 6 weeks. Secondary outcomes were OCT macular volume and perioperative and postoperative complications. RESULTS: Over the 6-week study, the median increase in foveal thickness in the study eye compared with that in the fellow eye was 11 microm (interquartile range [IQR] -21 to 23 microm) in the AquaLase group and 17 microm (IQR -11 to 33 microm) in the phacoemulsification group (P = .229). A subgroup analysis of diabetic patients found a median increase in foveal thickness in the study eye versus the fellow eye of 2 microm (IQR -14 to 23 microm) in the AquaLase group and 29 microm (IQR 11 to 41 microm) in the phacoemulsification group (P = .07). CONCLUSIONS: The results in this study suggest that AquaLase liquefaction cataract extraction is as safe as standard US phacoemulsification cataract extraction and may carry less risk for the development of postoperative cystoid macular edema. This may be most evident in diabetic patients.

Ockrim ZK, Sivaprasad S, Falk S, Roghani S, Bunce C, Gregor Z, Hykin P. · Royal Alexander Hospital, Corsebar Road, Paisley PA2 9PN, UK. · Br J Ophthalmol. · Pubmed #18420749 No free full text.

Abstract: AIM: To determine if repeated intravitreal triamcinolone improves best corrected visual acuity at 1 year compared with conventional laser therapy for persistent diabetic macular oedema. METHODS: 88 eyes with persistent clinically significant macular oedema, after at least one prior laser photocoagulation, were included in this prospective randomised controlled trial. 43 patients were randomised to 4 mg of intravitreal triamcinolone (TA) and 45 to laser photocoagulation. The primary endpoint was the proportion of patients who improved by 15 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters at 12 months in TA versus laser groups. Secondary endpoints were the change in mean best corrected visual acuity, difference in macular thickness and macular volume and adverse event reporting in particular elevated intraocular pressure at 12 months. RESULTS: Improvement in > or =15 ETDRS letters occurred in two of 42 patients in the TA group (4.8%) and in five of 41 (12.2%) patients in the laser group (p = 0.265). At baseline, the mean ETDRS scores at baseline were 54.4 letters in the TA group and 53.0 letters in the laser group. At 12 months, these were 54.5 and 54.6, respectively. Optical coherence tomography showed a reduction in central macular thickness of 82.0 microm with TA and 62.3 microm with laser at 12 months. There was one case of sterile endophthalmitis. 22 out of 43 patients in the triamcinolone group required ocular antihypertensives. CONCLUSION: This study did not show a benefit from intravitreal triamcinolone over conventional laser therapy for patients with chronic diabetic macular oedema.

Patel PJ, Chen FK, Ikeji F, Xing W, Bunce C, Da Cruz L, Tufail A. · Moorfields Eye Hospital, London, United Kingdom. · Invest Ophthalmol Vis Sci. · Pubmed #18326734 links to  free full text

Abstract: PURPOSE: To determine the repeatability of Stratus optical coherence tomography (OCT) measures of retinal thickness and volume in patients with neovascular age-related macular degeneration (nAMD) METHOD: Fifty-one eyes of 51 consecutive patients with nAMD underwent an OCT imaging session in which two fast macular thickness map (FMTM) protocol scans sets were acquired by a single experienced operator certified for clinical trials work. Coefficients of repeatability for each of nine Early Treatment of Diabetic Retinopathy Study (ETDRS)-like regions, foveolar center-point retinal thickness (CPT) and total macular volume (TMV), were calculated. Scans were analyzed retrospectively for errors in retinal boundary placement by two observers, with revised coefficients of repeatability calculated after excluding any scan sets with significant segmentation error. RESULTS: The coefficient of repeatability for the central 1-mm macular subfield was 67 mum (23%) and was less than 75 mum for all macular subfields. There was much larger variability in the center-point thickness measure, with a coefficient of repeatability of 88 mum (32%) for the automated center-point thickness (ACPT). After excluding nine scan set pairs with significant segmentation error, the coefficient of repeatability for the central 1-mm macular subfield was reduced to 50 mum (19%). CONCLUSIONS: OCT-derived retinal thickness measurements are subject to considerable measurement variability in patients with nAMD. Changes in central macular thickness of more than 50 mum may better reflect true clinical change in scan sets without significant segmentation error and may be used to guide the retreatment of patients with nAMD in clinical trials and clinical practice.

Vaclavik V, Vujosevic S, Dandekar SS, Bunce C, Peto T, Bird AC. · Moorfields Eye Hospital, London, United Kingdom. · Ophthalmology. · Pubmed #17599415 No free full text.

Abstract: PURPOSE: To determine if integrity of the retinal pigment epithelium (RPE)/photoreceptor complex as assessed by autofluorescence imaging can be predicted on the basis of visual acuity (VA), size, or fluorescein angiographic characteristics of the lesion in the early stage of choroidal neovascularization in age-related macular degeneration (AMD). DESIGN: Prospective, observational, consecutive case series. PARTICIPANTS: Seventy-nine eyes of 78 patients with untreated early-stage subfoveal neovascular AMD. METHODS: Digital color fundus photography and fluorescein angiography were carried out by certified photographers using the same camera throughout the study. Confocal scanning laser ophthalmoscopy images were obtained using a retinal angiograph. Autofluorescence images were compared with digital fluorescein angiography and fundus color photographs using IMAGEnet. MAIN OUTCOME MEASURES: Autofluorescence at the macula was correlated with VA, angiographic lesion characteristics, lesion size, and length of symptoms. RESULTS: Of the 79 eyes studied, 40 had classic and predominantly classic choroidal neovascularization, 10 had minimally classic, 29 had occult, 75 were subfoveal, and 4 were juxtafoveal. In 54 eyes, autofluorescence was continuous at the central macula, and this correlated significantly with VA, lesion size, and symptom length but not choroidal neovascularization type. However, there was considerable overlap between the 2 groups such that the integrity of RPE autofluorescence could not be predicted on the basis of these criteria. CONCLUSION: Intact autofluorescence at the macula in early choroidal neovascularization correlates with VA, lesion size, and symptom length but not lesion type. None predict with any certainty the integrity of the outer retina. Our data suggest that the RPE/photoreceptor complex may be intact at the macula for several months in the presence of choroidal neovascularization, suggesting that VA might be rescued if treatment were effective in suppressing neovascular growth without damaging the RPE/retina complex, although this remains to be tested. It would be sensible to assess autofluorescence in treatment protocols to test this concept because it may be a marker for earlier disease and predict outcomes of treatment.

Essex RW, Tufail A, Bunce C, Aylward GW. · Moorfields Eye Hospital, City Road, London EC1V 2PD, UK. · Br J Ophthalmol. · Pubmed #17446505 No free full text.

Abstract: PURPOSE: To present the 2-year outcomes of surgical removal of non-age-related macular degeneration (AMD)-related choroidal neovascular membranes and to evaluate any association between visual outcome and baseline clinical factors. METHODS: Retrospective consecutive case series. All patients who had surgery for non-AMD-related choroidal neovascularisation (CNV) between November 1997 and March 2003 under the care of a single surgeon (WA) were included in the study. Baseline data including patient age, duration of subfoveal CNV, preoperative visual acuity (VA), lesion size, lesion components and aetiology were collected. The primary outcome was VA change with secondary outcomes retinal detachment, operative peripheral retinal break formation, CNV recurrence and cataract. RESULTS: A total of 52 eyes were included in the study. The aetiology of CNV was: punctate inner choridopathy 21 (40%); idiopathic 8 (15%); pathologic myopia 6 (12%); ocular histoplasmosis syndrome 1 (2%); and other 16 (31%). The mean age of patients was 41(range 14-72) years. 24-month follow-up was available for 41 (80%) eyes. The mean logMAR equivalent baseline acuity was 1.1 and mean lesion size 1.2 disc areas. An improvement in VA >1 Snellen line was noted in 26 (63%) eyes, whereas 10 (24%) eyes remained the same (within 1 line) and 5 (12%) lost >1 line of acuity. Improvement in VA was associated with worse baseline VA (84% for eyes with VA <or=6/36 vs 31% for those with VA>6/36, p=0.001). No evidence of association between 2-year visual outcome and any other baseline factor under study was observed. Peripheral retinal breaks were noted in 5 (10%) eyes at the time of surgery, and 3 (5.8%) eyes developed postoperative retinal detachments. Persistent/recurrent CNV was noted in 17 (33%) eyes. The median time to presentation of CNV in these eyes was 27 (range 2-172) weeks. Five eyes underwent cataract surgery during the follow-up period. The mean age of these patients was significantly higher than the mean age of those who did not require cataract surgery (57 vs 37 years, p=0.014). CONCLUSIONS: Surgical excision of non-AMD-related CNV resulted in improvement of VA in the majority of eyes. Worse presenting acuity was associated with better visual improvements.

Bunce C, Wormald R. · Research and Development, Moorfields Eye Hospital, London, UK. c.bunce@ ucl.ac.uk · Eye. · Pubmed #17332762 No free full text.

Abstract: AIM: The last complete report on causes of blindness in England and Wales was for data collected during April 1990 to March 1991. This current study sought to update these figures, with data collected during April 1999 to March 2000, and examine variation in cause by age group. METHODS: In England and Wales, registration for blindness is voluntary and is initiated by certification by a consultant ophthalmologist. The main cause of blindness was ascertained where possible for all certificates completed during April 1999 to March 2000 and tabulated by age group. RESULTS: A total of 34 410 BD8 certificates were received, of which 13 788 (40%) were for people certified as blind. Different causes predominated within different age groups. Age related macular degeneration (AMD) was the lead cause in those aged 65 years and above, diabetic retinopathy was the lead cause in people of working ages (16-64 years), whereas cerebral visual impairment and disorders of the optic nerve accounted for over 40% of blind certificates completed for children. CONCLUSION: Estimates of vision impairment based on certifications for blindness in England and Wales are likely to be imprecise. They do, however, give some measure of the burden at hospital level of sight impairing eye conditions. If factors determining the imprecision remain constant, temporal monitoring of causes may enable changes and development of new conditions leading to vision impairment to be detected.

Bunce C, Wormald R. · Research & Development, Moorfields Eye Hospital, City Road, London, UK. · BMC Public Health. · Pubmed #16524463 links to  free full text

Abstract: BACKGROUND: Prevention 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. METHODS: Registration 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. RESULTS: 13,788 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 65's where figures have more than doubled. CONCLUSION: The 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.

Owens SL, Bunce C, Brannon AJ, Xing W, Chisholm IH, Gross M, Guymer RH, Holz FG, Bird AC, Anonymous00290. · Moorfields Eye Hospital, London, United Kingdom, and the Universitätsklinikum Benjamin Franklin, Berlin, Germany. · Am J Ophthalmol. · Pubmed #16458680 No free full text.

Abstract: PURPOSE: The Drusen Laser Study evaluated macular laser to prevent choroidal neovascularization (CNV) and vision loss in high-risk age-related maculopathy (ARM). DESIGN: Prospective, interventional, randomized, controlled clinical trial in five hospital centers. METHODS: Patients in the unilateral group had neovascular ARM and drusen in the study eye. Study eyes were randomized to laser-treated or no-laser groups. For patients in the bilateral drusen group, eyes were randomized to right eye, laser or no laser; and left eye, alternative. Laser treatment comprised 12 argon spots. Outcome was best-corrected visual acuity and CNV signs, which were monitored for 3 years. RESULTS: In the unilateral group, vision loss occurred in 21 (28.8%) of 73 patients in laser vs 13 (19.7%) of 66 no-laser patients (P=.214). Incidence of CNV was 27 (29.7%) of 91 in laser vs 15 (17.65%) of 85 no-laser patients (P=.061). CNV onset was approximately 6 months earlier in laser-treated compared with no-laser patients (P=.05). In the bilateral group, vision loss occurred in six (8.3%) of 72 laser-treated vs 10 (13.9%) of 72 fellow eyes (P=.3877). CNV incidence was 12 (11.6%) of 103 in laser-treated vs seven (6.8%) of 103 fellow eyes (P=.225). There was no difference in onset of CNV. CONCLUSIONS: Results do not support prophylactic laser of the fellow eye of patients with neovascular ARM. Its role in patients with bilateral drusen remains unclear.

Benson SE, Grigoropoulos V, Schlottmann PG, Bunce C, Charteris DG. · Vitreoretinal Research Unit, Moorfields Eye Hospital, London, England. · Arch Ophthalmol. · Pubmed #16344435 No free full text.

Abstract: OBJECTIVE: To use optical coherence tomography to assess the in vivo pathologic findings associated with incomplete visual recovery in patients who have undergone anatomically successful surgery to treat proliferative vitreoretinopathy. METHODS: Eligible patients were recruited in vitreoretinal outpatient clinics between April 1, 2002, and July 31, 2003. Patients were included who had undergone anatomically successful vitreoretinal surgery to treat proliferative vitreoretinopathy and, at least 3 months after surgery, had postoperative vision worse than expected (< or =6/12) with no identifiable cause at clinical examination. Patients underwent optical coherence tomography, stereo fundus fluorescein angiography was performed in a cohort of patients, and angiographic findings were compared with those on the optical coherence tomograms. Relevant clinical data were collected retrospectively from patient case notes. RESULTS: A total of 35 patients were recruited. Optical coherence tomograms revealed cystoid macular edema in 23 patients (66%) but did not identify any other specific intraretinal disease. Location of edema (outer or inner retina), determined with stereo fundus fluorescein angiography and optical coherence tomography, correlated well. CONCLUSIONS: Optical coherence tomography is a useful diagnostic tool for assessing poor postoperative visual acuity and can reveal disease undetected at clinical examination. Cystoid macular edema is a common finding on optical coherence tomograms in eyes with incomplete visual recovery after anatomically successful surgery to treat proliferative vitreoretinopathy.

Thomas D, Bunce C, Moorman C, Laidlaw AH. · Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. · Retina. · Pubmed #16205568 No free full text.

Abstract: PURPOSE: To determine prospectively among patients with diabetic macular edema (DME) the frequency of a clinically evident taut thickened posterior hyaloid (TTPH), optical coherence tomography (OCT) signs suggestive of partial vitreomacular separation (PVMS), and OCT evidence of subretinal fluid (SRF) and to investigate for associations between these findings. METHODS: In a prospective case series, patients with DME despite previous laser treatment were examined for the presence of a TTPH. OCT was performed to investigate for PVMS and SRF. RESULTS: One hundred forty patients and eyes were included in the study. A TTPH was present in six patients (4%). PVMS was present in 14 (10%) of 140 patients with DME, of whom 5 also had a TTPH. SRF was present in 15 (11%) of 140 patients, of whom 4 had TTPH. OCT showed that 66% of patients with SRF and DME had neither a clinical TTPH nor partial posterior hyaloid separation. CONCLUSION: A TTPH was found in 4% of subjects with DME. Partial posterior hyaloid separation and SRF may be found in patients who do not have a TTPH. SRF in patients with DME may not be tractional.

Patel JI, Hykin PG, Schadt M, Luong V, Bunce C, Fitzke F, Gregor ZJ. · Moorfields Eye Hospital, London, UK. · Eye. · Pubmed #16052254 No free full text.

Abstract: INTRODUCTION: Focal macular photocoagulation for clinically significant macular oedema (CSME) is the proven method for treatment of this condition, but with little chance of visual improvement. Pars plana vitrectomy (PPV) may produce resolution of macular oedema and improvement in visual acuity. However, there have been no randomised trials to ascertain role of vitrectomy in the management of persistent CSME. METHODS: Patients with persistent CSME despite previous macular photocoagulation and Snellen visual acuity 6/15 to 6/60 were recruited. Dilated fundoscopy, best-corrected visual acuity including Early Treatment Diabetic Retinopathy Study (ETDRS) vision, ocular coherence tomography and fundus fluorescein angiography (FFA) at baseline and up to 12 months post-treatment was performed. Exclusion criteria were signs of posterior vitreous detachment, macular traction or the taut posterior hyaloid face syndrome, or macular ischaemia on FFA. In all, 20 patients were randomised (10 in each arm) to either standard macular photocoagulation or PPV and removal of the posterior hyaloid face. RESULTS: Of the 20 patients recruited, seven patients completed the protocol in the vitrectomy and eight in the laser arms, respectively. There was little evidence of any difference in the foveal thickness at 12 months between the two treatment arms despite a gradual improvement. Only one patient, from the vitrectomy arm, suffered moderate visual loss (defined as loss of 15 ETDRS letters) (our primary outcome). DISCUSSION: In this pilot RCT, standard PPV provides little visual benefit compared to macular photocoagulation, but a larger definitive study is required to confirm this early appraisal.

Patel N, Ohbayashi M, Nugent AK, Ramchand K, Toda M, Chau KY, Bunce C, Webster A, Bird AC, Ono SJ, Chong V. · Ocular Immunology, Institute of Ophthalmology, University College of London, Bath Street, London WC1V 9EL, UK. · Immunology. · Pubmed #15946260 links to  free full text

Abstract: Age-related macular maculopathy (ARM) and age-related macular degeneration (AMD) are the leading causes of blindness in the Western world. Despite the magnitude of this clinical problem, very little is known about the pathogenesis of the disease. In this study, we analysed the sera (using indirect immunohistochemistry and Western blot analysis) from a very large cohort of such patients and normal age-matched controls to detect circulating anti-retinal antibodies. Patients with bilateral drusen (n = 64) and with chorioretinal neovascularization (CNV) (n = 51) were recruited in addition to age-matched control subjects (n = 39). The sera were analysed for anti-retinal immunoglobulins on retinal sections. The data were then correlated with the clinical features graded according to the International Classification and Grading System of ARM and AMD. The sera of patients with drusen (93.75%) and CNV (82.27%) were found to have a significantly (P = 0.02) higher titre of autoantibodies to the retina in comparison with controls (8.69%), indicating significant evidence of involvement of the immune process in early stages of AMD. Subsequent statistical analysis of the drusen group showed significant progressive staining (P = 0.0009) in the nuclei layers from early to late stages of ARM. Western blotting confirmed the presence of anti-retinal immunoglobulins to retinal antigens. As anti-retinal immunoglobulins are present in patients with bilateral drusen and exudative AMD, these antibodies could play a significant role in the pathogenesis of AMD. Whilst we do not have evidence that these antibodies precede disease onset, the possibility that their presence might contribute to disease progression needs to be investigated. Finally, the eventual identification of the target antigens detected by these antibodies may permit the future development of new diagnostic methods for ARM and AMD.

Scholl HP, Dandekar SS, Peto T, Bunce C, Xing W, Jenkins S, Bird AC. · Institute of Ophthalmology and Moorfields Eye Hospital, London, United Kingdom. · Ophthalmology. · Pubmed #14711724 No free full text.

Abstract: OBJECTIVE: To compare 35-mm stereoscopic slide transparencies with digitized nonstereoscopic images (resolution 1024x768 pixels) for grading abnormalities in age-related maculopathy (ARM) and age-related macular degeneration (AMD). DESIGN: Comparative observational case series. PARTICIPANTS: Twenty-five patients (50 eyes) with ARM and/or AMD. METHODS: Twenty-five patients with ARM/AMD in at least 1 eye were randomly selected from a large ongoing collection of clinical data and DNA in a tertiary referral United Kingdom population. Retinal photography was performed with mydriasis using the Zeiss FF-series 30 degrees fundus camera on Ektachrome slide transparency film. The images were centered on the macula. The color transparencies were then digitized. The grading process has been set up based on the International ARM Epidemiology Study Group. All images were independently graded by 3 retinal specialists. Both kappa statistics and exact agreement were calculated to assess agreement between and within observers and between the 2 master copies derived from the gradings of the color slides and digitized images. MAIN OUTCOME MEASURE: Agreement between the 2 master copies derived from the gradings obtained from stereoscopic slide transparencies and digitized nonstereoscopic images. RESULTS: For small hard and intermediate soft drusen, agreement ranged between 77% and 91% (kappa, 0.56-0.72) and 83% and 93% (kappa, 0.31-0.64), respectively, for the 3 macular subfields. Agreement for the presence of hyperpigmentation was 12% to 56% (kappa, 0.00-0.27). Agreement was 94% to 96% (kappa, 0.80-0.82) for the presence of geographic atrophy and 93% (kappa, 0.78) for the area covered. For the presence of choroidal neovascularization (CNV), agreement was 94% to 98% (kappa, 0.81-0.88), and it was 95% (kappa, 0.83) for the area covered. For individual features of CNV, exact agreement was 88% to 96% (kappa, 0.22-0.49). In 3 cases of geographic atrophy and 2 cases of CNV, the lesion was missed on digitized images. CONCLUSIONS: Because of the close agreement for most categories between the grading of stereoscopic color slides and digitized images, digitized nonstereoscopic color images prove to be useful for grading ARM and AMD.

Scholl HP, Peto T, Dandekar S, Bunce C, Xing W, Jenkins S, Bird AC. · Institute of Ophthalmology, Moorfields Eye Hospital, 162 City Road, EC1 V2PD, London, UK. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #12545291 No free full text.

Abstract: PURPOSE. To introduce a revised version of the grading system established by the International ARM Epidemiological Study Group for identifying and quantifying abnormalities of age-related maculopathy (ARM) and age-related degeneration (AMD) and to investigate its reliability, specifically the inter- and intra-observer variability. METHODS. Fifty eyes of 25 patients with ARM or AMD in at least one eye were randomly selected from a large ongoing collection of clinical data and DNA in a tertiary referral UK population. Stereoscopic color fundus photographs were taken with a 30 degrees fundus camera and were centered on the macula. Presence and severity of fundus abnormalities in ARM and AMD were graded using a grid to define macular subfields and standard circles to define the size of lesions. Inter-observer variability was assessed by having three retinal specialists evaluate the color slides and intra-observer variability by re-grading the same set. RESULTS. The inter-observer agreement for all subfields was fair to substantial for small hard drusen (70-89%; kappa=0.26-0.63) and intermediate soft drusen (76-94%; kappa=0.27-0.69). Agreement ranged between 87% and 100%, between 50% and 92%, and between 78% and 100% for larger drusen, the presence of hyperpigmentation, and the presence of hypopigmentation, respectively. Agreement was moderate to almost perfect for the presence of geographic atrophy (88-98%; kappa=0.60-0.95) and substantial to almost perfect for the presence of choroidal neovascularization (84-100%; kappa=0.62-1.00). The intra-observer variability for the grading of drusen characteristics and pigmentary changes was similar in magnitude, but slightly greater for features of advanced AMD. CONCLUSION. Reproducibility was achieved using a revised version of the grading system established by the International ARM Epidemiological Study Group. This grading system may therefore be used for phenotyping of ARM and AMD.

Lois N, Holder GE, Bunce C, Fitzke FW, Bird AC. · Medical Retina Service, Moorfields Eye Hospital, City Road, London EC1V 2PD, England. · Arch Ophthalmol. · Pubmed #11231769 No free full text.

Abstract: OBJECTIVE: To determine if phenotypic subtypes exist in Stargardt macular dystrophy-fundus flavimaculatus (SMD-FFM). METHODS: A cross-sectional study of 63 patients with autosomal recessive SMD-FFM was undertaken. The age of onset, duration of symptoms, visual acuity, and clinical features on fundus examination, color fundus photographs, and fundus autofluorescence images were recorded. Electrophysiological tests, including pattern, focal, and full-field electroretinogram (ERG), electro-oculogram, and color-contrast sensitivity measurement, were also performed. RESULTS: Based on electrophysiological attributes (ERG), patients with SMD-FFM could be classified into 3 groups. In group 1, there was severe pattern ERG abnormality with normal scotopic and full-field ERGs. In group 2, there was additional loss of photopic function, and in group 3, there was loss of both photopic and scotopic function. Differences in scotopic or photopic function among groups were not explained on the basis of differences in age of onset or duration of disease. CONCLUSIONS: Patients with SMD-FFM can be classified into 3 groups based on the absence or presence of generalized loss of either photopic or photopic and scotopic function. It appears that these 3 groups may represent distinct phenotypic subtypes in SMD-FFM.