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Purpose: To quantify the difference in progression of nuclear sclerotic cataract using Scheimpflug image analysis in patients with idiopathic full-thickness macular hole who were randomized to have vitrectomy and gas tamponade or to be observed., Setting: Moorfields Eye Hospital, London, United Kingdom., Design: Prospective randomized placebo-controlled masked clinical trial., Methods: As part of the Moorfields Macular Hole Study, patients with full-thickness macular hole who were randomized to have vitrectomy and gas tamponade or who were observed were compared. Patients had Scheimpflug image analysis of the crystalline lens to evaluate nuclear sclerosis progression by the single-masked observer at baseline and 3, 6, 9, and 12 months postoperatively., Results: Ninety-eight patients had sufficient baseline data for analysis. At 3 months and 6 months, vitrectomy patients had significant increases in nuclear density compared with baseline (16.6% and 33.9%, respectively) (both P<.0001). In the observation group, nuclear density increased by 1.4% between baseline and 6 months (P = .92). At 6 months, the increase in nuclear density from baseline was 24 times greater in the surgical group than in the observation group (P<.0001). No correlation between the rate of nuclear sclerosis progression and age or baseline nuclear density was found., Conclusions: Rapid nuclear sclerosis progression was quantifiable by Scheimpflug image analysis in patients having surgery for idiopathic full-thickness macular hole.There was no [corrected] evidence of a correlation between age groups and the rate of cataract progression., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2012. Published by Elsevier Inc.)

Purpose: To determine the preretinal distribution of oxygen in advanced proliferative diabetic retinopathy, and to investigate the relationship between intraocular oxygen tensions and vitreous cytokine concentrations., Design: Comparative cross-sectional study., Methods: Oxygen levels were measured at sites in the vitreous and at the inner retinal surface using an optical oxygen sensor in 14 control subjects and in 14 subjects with advanced proliferative diabetic retinopathy who had developed tractional retinal detachments despite previous panretinal photocoagulation. The vitreous and plasma concentrations of 42 cytokines were measured using multiplex cytokine arrays and their correlation with intraocular oxygen tension was investigated., Results: The mean oxygen tension in the mid-vitreous in diabetic retinopathy was 46% lower than that in control subjects (P = .017). However, the mean preretinal oxygen tension at the posterior pole in diabetic retinopathy was 37% higher than in controls (P = .039). We measured significant alterations in the vitreous concentrations of 9 cytokines-eotaxin, Flt-3 ligand, growth-related oncogene (GRO), interleukin (IL)-6, IL-8, IL-9, IFN-inducible protein-10 (IP-10), macrophage-derived cytokine (MDC), and vascular endothelial growth factor (VEGF)-in advanced proliferative diabetic retinopathy, and found that oxygen tension at the posterior pole was directly correlated with vitreous VEGF concentration., Conclusion: We identified significant intraocular oxygen gradients in proliferative diabetic retinopathy. Our findings are consistent with the hypothesis that VEGF induces the development of neovascular complexes in the posterior retina that are richly perfused but nonetheless fail to redress hypoxia in the mid-vitreous. Upregulation of vitreous VEGF may be a consequence of retinal hypoxia at unidentified sites or of chronic inflammatory processes in advanced proliferative diabetic retinopathy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Blood-retinal barrier breakdown with macular edema is caused by many diseases, which modulate--via different growth factors--the integrity of the tight junctions. Starling's law predicts furthermore that macular edema will develop if the hydrostatic pressure gradient between capillary and retinal tissue is increased, for example in the presence of elevated blood pressure, or if the osmotic pressure gradient is decreased, for example when protein accumulates excessively in the extracellular space within the retina. The rationale for clinical treatment of macular edema is based on the understanding and the inhibition of these pathophysiological mechanisms. On the medical side, nonsteroidal anti-inflammatory drugs inhibit the production of prostaglandins and leukotrienes, and modulate fluid movement coupled to chloride movement. Corticosteroids block cyclooxygenase and interleukin, downregulate vascular endothelial growth factor (VEGF) and decrease the phosphorylation of occludin, thereby increasing the tightness of the blood-retinal barrier. Carbonic anhydrase inhibitors are thought to modulate the polarized distribution of carbonic anhydrase at the level of the retinal pigment epithelium via extracellular pH gradients and thus the fluid resorption from the retina into the choroid. Anti-VEGF agents restore occludin proteins in the blood-retinal barrier and reduce protein kinase C activation. On the surgical side, the beneficial effect of vitrectomy with release of traction on the macula is explained by an increase in tissue pressure and a lowering of the hydrostatic pressure gradient, reducing the water flux from blood vessels into retinal tissue. The therapeutic action of vitrectomy in nontractional edema is thought to be based on two mechanisms: increased oxygen transport between the anterior and posterior segments of the eye and the removal of growth factors which are secreted in large amounts into the vitreous during proliferative vasculopathies., (2010 S. Karger AG, Basel)

Background: Outer retinal defects (ORDs) may occur after surgical closure of full thickness macular holes (FTMH) and be associated with delayed visual recovery. This may be due to the nature of the subretinal fluid (SRF) cuff and/or the loss of retinal elements., Methods: Vitrectomy with internal limiting membrane (ILM) peel was performed for FTMH. After fluid-air exchange, SRF was either aspirated from the hole (group 1) or left in situ (group 2). The SRF specimens obtained were examined by light microscopy and correlated with optical coherence tomography (OCT)., Results: In group 1, cellular material was found in 6 out of 12 cases. Photoreceptors were seen in 3 and macrophages in 3 cases. Nine of 12 holes closed and ORDs were seen in 3 of these. In group 2, 7 out of 8 holes closed, with 4 having ORD. There was no difference in visual acuity (LogMAR) for closed holes at 3 months between groups 1 (0.61, range 0.3-1) and 2 (0.51, range 0.3-0.78) nor between patients with ORD (0.57, range 0.3-1.0) or without ORD (0.57, range 0.3-1.0)., Conclusions: SRF from FTMH may contain macrophages and photoreceptors. Such photoreceptor loss may contribute to reduced retinal function. ORDs occur commonly in spite of fluid aspiration, but their presence is still compatible with good vision. Aspiration of SRF did not appear to confer added benefit in this series.

Objective: To examine the effect of a unilateral epiretinal membrane (uERM) on visual acuity, stereopsis, and motor fusion in patients before and after successful surgery to remove the membrane., Design: Cohort study., Participants: Twenty-seven consecutive patients undergoing surgery to remove an idiopathic uERM and 30 normal control subjects., Methods: Patients underwent full orthoptic examination before and between 3 and 6 months after surgery to remove a uERM. Stereoacuities were analyzed statistically using the Wilcoxon signed-rank test, Mann-Whitney U test, and Spearman correlation. Motor fusion ranges and visual acuities were compared using paired and unpaired t tests, with correlations examined by linear regression., Main Outcome Measures: Snellen visual acuity, TNO (stereoscopic acuity test of the Netherlands; Netherlands Organisation for Applied Scientific Research; Laméris Ootech BV, Nieuwegein, the Netherlands) and Titmus stereoacuity, motor fusion range., Results: Postoperative acuity and improvement in visual acuity after removal of a uERM were better in patients with a shorter duration of symptoms. Stereoacuity was substantially reduced in the presence of a uERM (TNO, P<0.001; Titmus, P<0.001; Mann-Whitney U test), as were total motor fusion ranges at near and distance (near P = 0.002; distance P = 0.015; t test). Stereoacuity was worse in patients with symptoms of longer duration (TNO, P = 0.21; Titmus, P = 0.045; Spearman rank correlation). After successful surgery, stereoscopic function improved. This improvement occurred mainly in those patients with better preoperative stereoacuity and a shorter duration of symptoms., Conclusions: Improvement in visual acuity after surgery was greater in patients with visual symptoms of shorter duration. A uERM adversely affected stereoscopic function, an effect that increased with time. The best monocular and binocular visual outcomes occurred in those patients who had earlier surgery.

Purpose: To compare the effects of intravitreal triamcinolone and macular grid laser photocoagulation on the vitreomacular relationship in diffuse diabetic macular edema., Methods: Review of optical coherence tomography images gathered in a prospective, interventional randomized clinical trial., Setting: Institutional Practice., Procedures: Seventy-seven optical coherence tomography images of 88 consecutive patients entered into a randomized clinical trial of the treatment of persistent diffuse diabetic macular edema were reviewed by two independent observers. All patients in the trial had diabetic macular edema following at least two macular grid laser treatments and were randomized to intravitreal injections of 4 mg triamcinolone or to further macular grid laser. Optical coherence tomography images were recorded at baseline, 4, 8, and 12 months and the patterns of vitreomacular relationship were classified into six categories., Main Outcome Measures: The patterns of vitreomacular relationship in the two groups were compared and correlated with the response to treatment. Outcome measures were defined as changes in best-corrected visual acuity Early Treatment Diabetic Retinopathy Study letters and central macular thickness on optical coherence tomography., Results: Six eyes had peri-foveal vitreous detachment with or without traction in each group at baseline. At 12 months, the prevalence of peri-foveal vitreous detachment was significantly higher after intravitreal triamcinolone (n = 11) than macular grid laser (n = 8). These patients had poorer visual outcome (P = 0.01) and increased central macular thickness (P = 0.002). The development of complete posterior vitreous detachment was associated with significantly decreased central macular thickness (P = 0.001) but not better visual outcome (P = 0.72)., Conclusion: These results suggest that posterior hyaloid changes may play a more influential role in the response to intravitreal triamcinolone than laser treatment for diffuse diabetic macular edema.

Aim: There are changes in blood flow during the clinical stages of diabetic retinopathy with increasing leukostasis and secondary elaboration of cytokines. This study evaluated the vitreous concentrations of haemodynamic-related (endothelin-1 (ET-1) and nitric oxide (NO)), inflammatory and anti-inflammatory (interleukin-1 receptor antagonist, IL-1 Ra) cytokines in the diabetic patients (with nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR)), compared them with those of control patients (full thickness macular hole, FTMH) and correlated to macular structural indices., Method: Vitreous samples from five FTMH patients representing normal controls were analysed together with the vitreous samples of 15 patients with NPDR and five with PDR. The vitreous concentrations of nitrite (total NO), ET-1, and prostacyclin was determined using ELISA kits (R&D Systems, Minneapolis, MN, USA) according to the manufacturer's instructions. A sandwich luminescent immunoassay technique was used to determine IL-1beta and IL-1 Ra concentrations., Results: In the different clinical groups, there were no differences in the vitreous NO and prostacyclin concentrations. In NPDR, the median ET-1 concentration (0.7 pg/ml SD +/-0.8 pg/ml) was significantly reduced (P<0.05), compared to PDR (6.35 pg/ml SD +/-0.6 pg/ml) and FTMH (3.6 pg/ml SD +/-0.14 pg/ml). Its concentration also positively correlated with foveal thickness and macular volume (P<0.05) in patients with NPDR and macular oedema. IL-1 beta was detected in PDR, and diabetic patients demonstrated a lower concentration of the anti-inflammatory cytokine IL-1 Ra., Conclusion: Reduced concentrations of ET-1 in NPDR may reflect the haemodynamic changes of NPDR. The IL-1 Ra concentration suggests a change in the anti-inflammatory environment of the diabetic retina.

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.

Purpose: A prospective study to evaluate the macular structural and functional effects of pars plana vitrectomy (PPV) for persistent diffuse clinically significant macular oedema (CSMO)., Method: A total of 12 patients with persistent diffuse CSMO were recruited and underwent assessment including best-corrected visual acuity, fundus fluorescein angiography, optical coherence tomography (OCT) and fine matrix mapping (FMM) at baseline and over a period of a year poststandard three-port PPV., Results: The median baseline ETDRS letters score for all 12 patients was 52 (range 41-63) while at 12 months it had increased to 65 (range of 27-68), an improvement of two complete ETDRS lines (P=0.037). Similarly, there was an improvement in the perifoveal cone thresholds (P=0.02). The foveal thickening for all 12 patients ranged from a median of 183 to 751 microm (normal range 126-180 microm) and the macular volume ranged from a median of 2.13 to 6.42 mm(3) (normal <1.66 mm(3)). After surgery, both the median foveal thickness (from 334 to 280 microm) and median macular volume (from 3.24 to 2.61 mm(3)) demonstrated decreases over 12 months (P=0.01). On baseline OCT, the patients fell into two anatomically distinct groups: Group 1 (n=4) had a dome-shaped thickened macula with a partial posterior hyaloid separation and a significantly higher foveal thickness and macular volume than Group 2 (n=8) which had a diffuse low-elevation profile of the thickened macula (P=0.007)., Conclusions: In this prospective study of PPV for persistent fovea-involving CSMO there was structural and functional improvement.

The aim of the study was to determine anatomical and growth factor profiles in patients with clinically significant macular oedema (CSMO) undergoing pars plana vitrectomy (PPV). Twenty patients with moderate nonproliferative diabetic retinopathy (NPDR) with persistent CSMO underwent PPV. Patients had baseline and postoperative clinical assessment including Ocular Coherence Tomography (OCT). Baseline vitreous and aqueous and serial postoperative aqueous samples were analysed for vascular endothelial growth factor-A (VEGF-A), pigment epithelium derived Factor (PEDF) and other factors (pg/ml) including hepatocyte growth factor, MMP 9, soluble flt-1 Receptor, and TGF beta1 by ELISA. Vitreous from patients with full thickness macular holes (8) and proliferative diabetic retinopathy (22) were collected for comparison as controls. Vitreous VEGF-A concentration in the NPDR group was 957 pg/ml compared to 239 pg/ml in the macula hole (FTMH) control (p < 0.0001) and 596 pg/ml compared to PDR (p = 0.006). The median diabetic vitreous PEDF concentration was 1.36 microg/ml (FTMH 2.6 microg/ml p = 0.05). In NPDR, it was higher (1.59 microg/ml) than PDR (1.27 microg/ml) p = 0.02. There were changes to the HGF, soluble flt-1 Receptor and TGF b1 concentrations in the NPDR compared to either PDR or the normal state. In CSMO, two OCT profiles were identified: dome-shaped macular elevation (Group 1) (n = 4) and diffuse-low elevation profile (Group 2) (n = 16) which also showed differences in the postoperative median aqueous VEGF concentrations despite macular volume decreasing for both. The results suggest that there is an up-regulation of VEGF in the vitreous of the diabetic eye with a reciprocal decrease in PEDF. The structural and molecular differences between the two OCT macular profiles may explain the varying response to PPV in patients with diffuse CSMO.

Purpose: A prospective, comparative, nonrandomized study to evaluate the efficacy of pars plana vitrectomy (PPV) with and without inner limiting membrane (ILM) peeling for persistent diffuse clinically significant macular edema., Methods: Eighteen patients with persistent diffuse clinically significant macular edema despite laser photocoagulation were recruited for the study. Clinical assessment included determination of best-corrected visual acuity, fundus fluorescein angiography, optical coherence tomography, and perifoveal cone function testing. Eight patients underwent PPV with elevation and removal of the posterior hyaloid alone, and 10 patients underwent vitrectomy and ILM peeling. The follow-up was 12 months., Results: Patients with ILM peeling had improvement in foveal thickness (P = 0.07) and significant improvement in the macular volume (P = 0.039) 12 months after surgery but did not have significant improvement in Early Treatment Diabetic Retinopathy Study vision or perifoveal cone function. There was no significant difference in outcome parameters between the no peeling group and the ILM peeling group., Conclusions: In this prospective, comparative study of PPV with and without ILM peeling for diffuse clinically significant macular edema, structural improvement was seen but with limited visual improvement after ILM peeling.

Background/aim: Angiopoietin 1 and 2 interact with vascular endothelial growth factor (VEGF) to promote angiogenesis in animal and in vitro models. Although VEGF concentrations are elevated, there is little information regarding angiopoietin concentration in the vitreous of patients with diabetic retinopathy., Methods: Angiopoietin concentrations were measured by luminescence immunoassay in vitreous samples from 17 patients with non-proliferative diabetic retinopathy (NPDR) and clinically significant diabetic macular oedema (CSMO), 10 patients with proliferative diabetic retinopathy (PDR), and five patients with macular hole (controls) obtained at pars plana vitrectomy., Results: Angiopoietin 1 concentrations were low in patients with macular hole (median 17 pg/ml) while in NPDR with CSMO they were 2002 pg/ml (range 289-5820 pg/ml) and in PDR 186 pg/ml (range 26-2292 pg/ml). Angiopoietin 2 concentrations in NPDR with CSMO were a median of 4000 pg/ml (range 1341-14 329 pg/ml). For both macular hole and PDR patients angiopoietin 2 was below the limit of detection., Conclusions: Angiopoietin 2 concentration was twice that of angiopoietin 1 in NPDR with CSMO. Angiopoietin 2 is the natural antagonist of angiopoietin 1 which is thought to act as an anti-permeability agent. The predominance of angiopoietin 2 may allow VEGF induced retinal vascular permeability in patients with CSMO. The relatively low concentration of both angiopoietin 1 and 2 in patients with proliferative diabetic retinopathy may reflect the established nature of the neovascularisation in cases proceeding to vitrectomy.

Aims: To study the natural history and evaluate optical coherence tomography (OCT) and the retinal thickness analyser (RTA) in patients with macular microholes., Methods: The medical records of 22 patients with a well demarcated red intraretinal foveal or juxtafoveal defect were reviewed. Fluorescein angiography (FA), RTA, and OCT were performed. The main outcome measures were visual acuity (VA), and OCT and RTA characteristics of microholes. Long term follow up was available in 13 eyes of 12 patients., Results: The patients had a mean age of 50 years and a mean refractive error of -0.93 dioptres. The presenting symptom was a central scotoma in 14 eyes and metamorphopsia in eight eyes. All patients had a corrected VA ranging from 20/16 to 20/125, with 20 out of 24 eyes (83%) having a VA > or =20/40. Symptoms remained stable or improved in 16 out of 22 patients (72%). OCT 2 findings were normal but an abnormality of the outer retina and/or a defect of the retinal pigment epithelium (RPE) were demonstrated on OCT 3 in 15 of 18 eyes (83%). The RTA topographic map demonstrated a defect at the site of the microhole in two out of 12 eyes., Conclusion: Although biomicroscopic examination suggested an inner foveal defect, the OCT 3 scans demonstrated a localised abnormality of the outer retina and/or RPE which could not be resolved using OCT 2. Macular microholes have a favourable long term prognosis with stable VA. Bilateral involvement is uncommon.

Purpose: Removal of silicone oil after vitreoretinal surgery reduces potential complications of glaucoma and cataract and improves visual function in 30% of patients. We report the clinical findings of a series of patients who experienced unexpected and permanent visual loss after removal of silicone oil., Methods: Seven patients with visual loss after removal of silicon oil were investigated with best-corrected Snellen visual acuity (BCVA) assessment, fundus biomicroscopy, fluorescein angiography, optical coherence tomography, and electrophysiologic examination., Results: Six men and one woman (average age, 42.8 years.) presented with profound BCVA loss, averaging 4.7 Snellen lines (SD 1.4), after silicon oil removal. No other complications associated with oil removal were noted. The retina remained attached in all cases, no patient developed cystoid macular edema or epiretinal membrane, and optical coherence tomographic and fluorescein angiographic findings remained normal. Electrodiagnostic testing showed a range of abnormalities, with the majority of patients showing severe macular dysfunction., Conclusions: We describe a new phenomenon of unexpected visual loss after oil removal in patients with good visual potential. The pathogenesis remains obscure.

Aims: To examine the effect of a unilateral full thickness macular hole on sensory and motor binocular function and to study recovery after successful surgical closure., Methods: Twenty eight consecutive patients undergoing surgery for a unilateral macular hole underwent orthoptic examination, including measurements of Titmus and TNO stereoacuity and motor fusion range before surgery. Twenty three patients had successful anatomical closure. Fifteen of these patients, who had both improved acuity in the operated eye following surgery and were available for further testing, underwent repeat orthoptic assessment 2-7 months after surgery., Results: In all patients stereoacuity was reduced before surgery, but few patients were subjectively aware of a deficit of depth perception affecting their everyday life. In those patients with improved Snellen acuity after surgery, stereoacuity measured by the Titmus stereotest also improved significantly, but not that measured by the TNO test. Two patients were aware of a subjective improvement in depth perception. Motor fusion was markedly reduced compared to normal before surgery, with only limited recovery after surgery., Conclusion: A unilateral macular hole notably reduced both stereoacuity and motor fusion. Successful closure improved the deficit in stereoacuity associated with the hole when measured by a stereotest using contoured stimuli. The majority of patients were not subjectively aware of the deficit in stereoacuity or its improvement following surgery.

Purpose: To describe a patient with resolved hypotony maculopathy with a persistent retinal fold (despite normalization of intraocular pressure [IOP]) who underwent successful surgical intervention by vitrectomy, internal limiting membrane peel, and gas tamponade., Design: Interventional case report., Methods: A 55-year-old man with a hypotony-induced macular retinal fold that did not improve following normalization of IOP underwent vitrectomy, internal limiting membrane peeling, and gas injection. Optical coherence tomography scans were performed both before and after surgery., Results: Best-corrected visual acuity (BCVA) improved from 6/60 preoperatively to 6/9, with improvement in distortion. On repeat optical coherence tomography examination, the macular retinal fold had resolved., Conclusion: Vitrectomy, internal limiting membrane peeling and gas tamponade may be useful for cases of resolved hypotony maculopathy complicated by a persistent macular fold after normalization of IOP.

Objectives: To determine the benefits of idiopathic full-thickness macular hole (FTMH) surgery compared with observation and to evaluate the use of autologous serum as an intraoperative adjunct., Methods: A randomized clinical trial was performed to evaluate the anatomic and visual benefits of FTMH surgery for lesions of 9 months or less symptom duration and visual acuity of 20/60 or less. We compared surgery with natural history and determined whether use of intraoperative adjunctive autologous serum improves the surgical outcome. Eyes were randomized to (1). observation, (2). vitrectomy, or (3). vitrectomy plus serum and were followed for 24 months to assess anatomic status and visual function., Results: In total, 185 eyes of 174 patients were enrolled. In the observation group, spontaneous closure of the FTMH occurred in 7 (11.5%) of 61 patients, with little or no change in overall acuity levels in 24 months. In contrast, the surgical groups had an overall closure rate of 80.6% (100/124) at 24 months, with 45% of eyes achieving Snellen acuity of 20/40 or greater. Surgical eyes had better median near acuity than observation eyes by 6 lines (N5 vs N14). Use of autologous serum did not seem to affect anatomic or visual results. At 24 months, 72 (58.1%) of 124 surgical eyes had undergone cataract extraction., Conclusions: Surgery for FTMH is safe and effective and is associated with significant visual improvement compared with the natural history. Autologous serum application does not enhance the results of surgery.

The success rate of retinal reattachment surgery has now reached over 90%. The major cause of failure is attributable to the development of proliferative vitreoretinopathy (PVR). It is a complex process comprised of events that are similar to those of the wound healing response with inflammation, migration and proliferation of a variety of cells. These membranes can exert traction and reopen previously closed retinal breaks, create new breaks, and distort or obscure the macula. In the early part of this century the success rate of retinal reattachment surgery was virtually nil and it was not until a better understanding of the pathophysiology of retinal detachment was gained that the success rate improved. It was Gonin who emphasised the relationship between vitreous detachment and traction resulting in retinal tears that led to treatment aimed at closing retinal breaks. To increase even further the final success rate in the treatment of 'simple retinal detachments' a better understanding of the risk factors for PVR is needed in patients presenting with acute retinal detachments. Such risk factors can be broadly divided under the headings of preoperative risk factors, best surgical management and possibly adjuvant therapy.

Objectives: To identify risk factors for retinal redetachment after removal of silicone oil. To determine the effectiveness of prophylactic laser in preventing retinal redetachment after removal of silicone oil., Design: A nonrandomized retrospective comparative interventional trial., Participants: Three hundred seventy-six patients undergoing vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment at one institution over a 4-year period. Two hundred eighty-seven patients with fully attached retinas subsequently underwent removal of silicone oil. One hundred thirty-eight cases had undergone prophylactic 360 degrees laser retinopexy before removal of silicone oil, either at the time of their final retinal reattachment procedure (n = 36) or as a separate supplementary procedure (n = 102)., Methods: A retrospective case note review was performed to identify clinical and demographic factors associated with increased or reduced odds of retinal redetachment after removal of silicone oil. Both univariate and multiple variable analysis were used to identify significant risk factors., Main Outcome Measures: Incidence of retinal redetachment after removal of silicone oil., Results: Median follow-up after removal of silicone oil was 272 days. Three hundred sixty-degree prophylactic laser retinopexy was associated with a reduction from 26% to 14% in the incidence of redetachment after removal of silicone oil (adjusted odds ratio, 0.42; 95% confidence interval, 0.22-0.78; P = 0.006). Patients requiring further retinal reattachment surgery after their first oil procedure were at twice the odds of re-detachment after oil removal (adjusted odds ratio, 2.10; 95% confidence interval, 1.03-4.26; P = 0.04)., Conclusions: The need for retinal reattachment surgery subsequent to a first silicone oil procedure was associated with twice the odds of retinal redetachment after removal of silicone oil. Prophylactic laser retinopexy may halve the incidence of retinal redetachment after removal of silicone oil.

Purpose: To report the occurrence of a full-thickness macular hole in the early postoperative period after uncomplicated phacoemulsification cataract surgery., Methods: Retrospective analysis of a consecutive series of eyes referred for treatment of a full-thickness macular hole after uncomplicated phacoemulsification cataract surgery., Results: In a 4-year period, five eyes with acute full-thickness macular hole after uncomplicated phacoemulsification cataract surgery were examined. Metamorphopsia and vision loss had occurred 2 to 8 (mean, 4.4) days after phacoemulsification. All eyes had attained normal corrected vision on day 1 postoperatively. A stage 2 full-thickness macular hole was present in four of the five, and a stage 3 full-thickness macular hole in one of the five eyes with acuities of 20/60--20/120 (median, 20/80). All five eyes had successful closure with early primary full-thickness macular hole surgery with visual improvement to 20/20-- 20/60 (median, 20/40)., Conclusion: Full-thickness macular hole may occur rarely during the early postoperative period after uncomplicated phacoemulsification, and early diagnosis and full-thickness macular hole surgery carries a favorable prognosis. The mechanisms underlying macular hole formation in these eyes are unclear.

Purpose: Choroidal neovascularisation (CNV) occurs rarely following laser photocoagulation for macular oedema in diabetic retinopathy, and its management is not well established. We report the clinical course and visual outcomes in a series of patients who underwent surgical extraction of the CNV membrane., Methods: A retrospective review of 4 cases was carried out., Results: Two women and 2 men, mean age 59.5 (range 58-62) years, were reviewed. The CNV developed 2-24 (mean 11) months after laser coagulation and resulted in decreased visual acuity to between 6/60 and HM. All underwent pars plana vitrectomy, extraction of the CNV membrane and fluid-air exchange. Follow-up ranged between 9 and 48 months. In 2 patients, the vision improved by 4 and 1 Snellen lines respectively and remained stable, in 1 patient it improved by 1 line initially but then regressed to CF, and in 1 patient it remained unchanged. Recurrence of CNV occurred in only 1 patient. Histological characteristics were those of CNV without evidence of photoreceptors., Conclusions: This study shows that surgical removal of post-laser CNV is technically feasible despite the previous laser scars and may have beneficial outcome. This surgical approach may provide a therapeutic option in such patients.

Objectives: To immunocytochemically characterize the neural and glial elements of idiopathic full-thickness macular hole (FTMH) opercula excised during vitrectomy, and to correlate them with the outcome of surgery., Methods: Opercula were collected from eyes undergoing vitrectomy for stage 3 FTMH and processed for transmission electron microscopy, light epifluorescence, and laser scanning confocal microscopy. Glia were identified using anti-glial fibrillary acid protein (GFAP), antivimentin, and anti-cellular retinaldehyde binding protein antibodies. Anti-phosphodiesterase gamma and antirhodopsin were used for cone and rod photoreceptors, and anticytokeratin was used for retinal pigment epithelium. The findings were correlated with the clinical data before and after surgery. For statistical analysis, data were combined with those of a previous study by the authors of 18 opercula., Results: Opercula from 12 consecutive eyes of 12 patients were studied. In all opercula, GFAP, vimentin, and cellular retinaldehyde binding protein-positive glia were present. Six (50%) of 12 opercula contained more than 5 photoreceptors with somata and internal photoreceptor fibres, but lacking outer segments, demonstrating strong immunoreactivity to anti-phosphodiesterase gamma without antirhodopsin reactivity consistent with cones. Further, 2 (17%) of 12 opercula showed few cones (1-5 cones), and 4 (33%) of 12 contained only glia. Clinicopathologic correlation of the 30 opercula from the 2 studies showed that eyes with opercula containing more than 5 photoreceptors were associated with a worse anatomical closure rate after initial surgery, compared with those with fewer than 5 photoreceptors (P =.004). Once closure had been achieved with reoperation, median postoperative vision was similar in both groups (20/40 and 20/60, respectively)., Conclusions: A spectrum of opercula occur in FTMH ranging from those containing only glia to those containing numerous cones. The extent of foveal neuroretinal tissue loss may affect the outcome of surgery.

Objective: To document ocular penetration of oral tamoxifen in patients being administered systemic therapy by measuring intraocular and serum levels of the drug in a series of patients undergoing elective ocular surgery., Design: Nonrandomized, prospective, comparative trial., Participants: Twenty-one eyes of 21 patients undergoing elective ocular surgery (cataract extraction or vitrectomy). Twenty patients were using the antiestrogen, tamoxifen, and one participant was not. Nine patients were excluded in the final analysis because of inadequate sample size., Intervention: Preoperative serum samples and perioperative aqueous samples, vitreous samples, or both were obtained for each patient, and these were analyzed for tamoxifen and its metabolites. Dilated fundus examination was performed before surgery on all patients., Main Outcome Measures: Evidence of tamoxifen, its metabolites, or both in the samples., Results: Tamoxifen was detected in all analyzed serum samples (range, 82.4-290.0 ng/ml.) from patients taking the medication and was found to have penetrated into both vitreous (range, 0.5-7.8 ng/ml) and aqueous (range, 0.5-3.9 ng/ml) cavities. No relationship was found between serum and intraocular levels., Conclusions: This study shows that tamoxifen penetrates intraocular fluids to varying degrees. The drug levels in aqueous and vitreous do not appear to correlate with serum levels. Evidence of tamoxifen retinopathy or keratopathy was not seen.

Aim: To examine epiretinal membranes of proliferative diabetic retinopathy (PDR) for the presence of selective matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs), in order to determine whether neovascularisation and fibrosis, characteristic of this complication of diabetes mellitus, are associated with specific anomalies of MMP or TIMP expression., Methods: The presence of selected MMPs and TIMPs was investigated in 24 fibrovascular epiretinal membranes of PDR, and the findings compared with that observed in 21 avascular epiretinal membranes of proliferative vitreoretinopathy (PVR) and five normal retinas. Specimens were examined for deposition of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase A (MMP-2), gelatinase B (MMP-9), and three tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, and TIMP-3)., Results: The results showed that unlike normal retina, which constitutively expresses MMP-1 and TIMP-2, a large proportion of PDR membranes (> 62%) stained for MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, and TIMP-3. There were no differences in the expression of these molecules when compared with PVR membranes. A characteristic staining for MMP-9 was observed within the perivascular matrix of PDR membranes, and there was a significant increase in TIMP-2 expression by PDR membranes (p= 0.036) when compared with PVR membranes., Conclusions: The findings that MMPs involved in degradation of fibrovascular tissue matrix, as well as TIMP-1 and TIMP-2, are found in a large proportion of PDR membranes, and that their expression does not differ from that of PVR membranes, suggest the existence of common pathways of extracellular matrix degradation in pathological processes leading to retinal neovascularisation and fibrosis.

Aim: To investigate the prevalence and the outcome of management of fibrovascular ingrowth (FVI) in eyes undergoing vitreous cavity washout (VCWO) following vitrectomy for diabetic retinopathy., Method: FVI was searched for at VCWO for in 19 consecutive eyes with proliferative diabetic retinopathy undergoing vitreous surgery for recurrent vitreous cavity haemorrhage over an 18 month period; the findings were correlated with the presence or absence of associated sclerotomy vessels externally. Eyes with richly vascularised ingrowths from the pars plana entry sites, as well as eyes with less extensive ingrowths but extensive retinal ablation applied at previous surgery for recurrent haemorrhage, underwent lensectomy and ciliary membrane dissection in addition to extensive retinopexy (n=6). Less severe cases received peripheral laser and cryotherapy only. The outcome of repeat surgery was studied prospectively in the 11 eyes with FVI., Results: 11 of the 19 eyes had a definite FVI from one or more of the original pars plana sclerotomies. In six of 11 eyes with FVI a large external episcleral vessel was present entering the original sclerotomy sites at which ingrowth was found peroperatively, but such sclerotomy vessels were also present in three of eight eyes with no FVI detected on the internal aspect of the sclerotomy. Two patients were lost to follow up and the remaining nine patients with FVI had no further vitreous cavity haemorrhage during initial follow up of 2-5 months., Conclusions: FVI has until now been considered an infrequent occurrence following vitrectomy for diabetic retinopathy. These findings would suggest that it is not uncommon and careful examination of the sclerotomy sites should be undertaken in all cases with recurrent haemorrhage and if FVI is found this should be treated appropriately.

Aim: Ophthalmological complications associated with Berger's IgA nephropathy comprise scleritis, episcleritis, keratoconjunctivitis as well as anterior uveitis. We present a new association of IgA nephropathy with a retinal vasculopathy., Methods: Presentation of two clinical cases., Results: Two patients presented with hematuria and epistaxis associated with a retinal vasculopathy characterised by teleangiectasies, capillary occlusion with retinal hemorrhages, neovascularisations and macular edema with decreased visual acuity. Fluorescein angiography showed zones of non-perfusion as well as vasculitic changes. A general medical exam revealed a normal arterial pressure but a slightly elevated creatinine. Immunological investigations for the presence of antibodies showed no positive results. Renal biopsy demonstrated mesangial proliferations with diffuse deposits of IgA. Over the course of a 2 year follow-up some of the retinal changes regressed under treatment with cortisone and visual acuity returned to normal. The teleangiectasies showed no progression., Conclusion: Berger's IgA nephropathy can be associated with a retinal vasculopathy which may be due to local deposition of IgA immune complexes in the retinal vessels.

Aims: To determine the visual and anatomical outcome of surgery for long standing idiopathic macular holes., Methods: A retrospective review of 24 eyes of all 22 patients who underwent surgery for idiopathic full thickness macular holes (FTMH) symptomatic for between 1 and 3 years. Postoperative follow up was for 6 months. Preoperative and postoperative visual acuities were recorded as well as the presence of anatomical closure of the hole., Results: The mean duration of symptoms was 18.21 (SD 5.42) months). Anatomical closure of the FTMH was achieved in 17 (70.8%) of the eyes at 6 months. The logMAR acuity of the group where closure was achieved improved by a mean of 0.31, equivalent to a change of Snellen acuity from 6/60 to 6/29. Where the hole remained open the acuity deteriorated by a mean logMAR of 0.11 lines, equivalent to a change of Snellen acuity from 6/60 to 5/60. Anatomical closure of the hole was associated with a significantly improved acuity over non-closure (p<0.001). The degree of visual improvement was independent of the preoperative visual acuity (Spearman correlation coefficient 0.03, p=0.888), though preoperative acuity was related to the final acuity (Spearman correlation coefficient 0.701, p<0.001). Over the study period, six patients required cataract surgery, one patient developed secondary glaucoma, and one a retinal detachment., Conclusions: Vitrectomy with intraocular gas tamponade and postoperative posturing is a well tolerated and effective intervention for long standing macular holes. Anatomical closure of the macular hole is associated with a significant improvement in visual acuity.

Purpose: To review the management by pneumatic retinopexy of 31 primary rhegmatogenous retinal detachments performed between August 1994 and December 1997., Methods: Ocular indications included superior retinal breaks, no evidence of proliferative vitreoretinopathy (PVR) and ability to posture. Patients with inferior breaks and/or areas of vitreoretinal degeneration were excluded. Surgery was performed under local anaesthetic using sulphur hexafluoride (SF6) or perfluoropropane (C3F8) gas injection. Transconjunctival cryotherapy or laser retinopexy was used to create permanent retinal adhesion. The mean length of patient follow-up was 11 months (range 5-24 months)., Results: Thirty-one patients (20 men, 11 women) with a mean age of 63.4 years (range 29-81 years) underwent pneumatic retinopexy which resulted in initial retinal reattachment in 22 patients. Two detachments recurred in the first month and a third at 4 months post-operatively, giving an anatomical reattachment rate with one procedure in 19 out of 31 eyes (61%). Of the 12 failures, 7 were reattached with one additional operation and one case reattached after multiple procedures, giving an overall reattachment rate of 87%. Post-operatively, new or missed breaks were present in 7 patients (22%) and PVR developed in 4 patients (13%). There was no difference in age, gender or extent of detachment between the failed and reattached groups and pseudophakia did not appear to be a poor prognostic factor., Conclusion: Pneumatic retinopexy can be a useful alternative to conventional rhegmatogenous retinal detachment surgery in carefully selected cases. A larger study addressing the influence of non-ocular factors is warranted.

Aims: To explore the relation between clinical course and timing of vitrectomy with the nature and intensity of intraocular inflammatory response in eyes with retained intravitreal lens fragments following complicated phacoemulsification., Methods: Prospective evaluation of 22 eyes with retained lens fragments with emphasis on corneal clarity, uveitis, intraocular pressure (IOP), timing of vitrectomy, and visual outcome. Numbers of different types of inflammatory cells in vitreous washings were counted, masked to clinical details, in three non-overlapping adjacent high power fields. Relations between clinical and pathological findings were assessed., Results: The IOP was raised in 19 eyes before vitrectomy and remained high in nine postoperatively. The latter had higher median total cell count (104 cells/mm(2)) than those with normal postoperative IOP (37 cells/mm(2)) but this difference was not statistically significantly different (p=0.17). Nine of 22 eyes underwent vitrectomy within 1 week of cataract surgery. Median total cell count in these eyes was 20 cells/mm(2) compared with 140 cells/mm(2) in eyes vitrectomised later-this difference was statistically significant (p <0.001). Final visual acuity was 6/12 or better in 13 eyes, these had fewer intravitreal inflammatory cells than the remaining six with poor visual outcome and no pre-existing cause for this (three patients excluded) (p=0.02). Macrophages were the predominant inflammatory cell type., Conclusion: There was significantly less inflammatory cell activity in eyes which had retained lens fragments removed early (within 1 week). Later removal was associated with persistently elevated IOP and poorer visual outcome.

Objectives: To determine whether ocular angioma can occur in the absence of von Hippel Lindau (VHL) syndrome, to define the clinical characteristics of sporadic (non-VHL) angioma, and to estimate a prevalence for sporadic ocular angioma., Design and Participants: A cross-sectional study of a cohort of patients with apparent sporadic ocular angiomatosis recruited from throughout the United Kingdom., Intervention: Clinical details and a family history were obtained for the patients in the cohort. Systematic ocular examination and further systemic screening were performed on the patients and relatives when possible. Leukocyte DNA was examined for VHL germline mutations., Main Outcome Measures: Patients with solitary and typical VHL-like ocular angioma, without clinical and family histories for VHL, were selected as possible sporadic (non-VHL) ocular angioma cases. An estimate of the population prevalence of sporadic (non-VHL) ocular angioma was made from patients presenting in the East Anglian region of the United Kingdom over a 25-year period., Results: From 32 patients referred, 17 had typical solitary ocular angioma and no evidence of other VHL complications in themselves or in family members. All 17 patients were negative for germline VHL mutations. The mean age of presentation was 30.9 years (median, 27.5; range, 3-52); 11 of 17 eyes suffered visual loss and 4 of 17 tumors occurred on the optic disc. The estimated prevalence of non-VHL ocular angioma was 9.0 x 10(-6), 95% confidence interval (CI) = 3.3 - 19 x 10(-6) (1 in 110,000 persons, 95% CI = 1 in 53,000-300,000)., Conclusions: Sporadic ocular angioma can occur in the absence of VHL disease but appears less prevalently than VHL itself. The age of presentation, degree of visual morbidity, complications, morphology, and anatomic location of tumors are similar to those seen in VHL disease.

Aim: To demonstrate the usefulness of a recently developed technique of imaging fundus autofluorescence and to compare it with the results of fluorescein angiography in the diagnosis and staging of macular holes., Methods: The intensity and distribution of fundus autofluorescence was studied in 51 patients with idiopathic macular holes and pseudoholes using a confocal laser scanning ophthalmoscope (cLSO) and the images were compared with those obtained by fundus fluorescein angiography., Results: Autofluorescence imaging demonstrated bright fluorescence of macular holes with appearance similar to that obtained by fluorescein angiography. In contrast macular pseuodoholes showed no such autofluorescence. The attached operculum in stage 2 macular holes and the preretinal operculum in stage 3 macular holes showed focal decreased autofluorescence. The associated retinal elevation and the cuff of subretinal fluid were less fluorescent compared with the background autofluorescence of the normal fellow eyes. Following successful surgical treatment the autofluorescence of the macular holes was no longer visible., Conclusion: Autofluorescence imaging with the cLSO makes the assessment of macular holes possible with an accuracy comparable with that of fluorescein angiography. Being non-invasive and rapid, autofluorescence imaging may become a useful alternative to fluorescein angiography in the assessment and the differential diagnosis of full thickness macular holes.

Purpose: This study aimed to determine the incidence of idiopathic full-thickness macular hole (FTMH) in normal fellow eyes and to evaluate the role of electrodiagnostic and psychophysical tests in identifying eyes at risk., Patients and Methods: A prospective longitudinal natural history study of a cohort of patients with unilateral holes and normal, asymptomatic fellow eyes without posterior vitreous detachment was conducted. Subjects underwent baseline examination, pattern reversal electroretinography, electro-oculography (EOG), and color contrast sensitivity (CCS) testing for protan, deutan, and tritan thresholds and were recalled for clinical examination at 18 months and 5 years., Results: At baseline, 114 patients were examined. Eighty were available for review at 18 months, of whom 6 had full-thickness macular holes develop in the fellow eye. At 5 years, 67 of the remaining 74 patients who had not developed holes at 18 months were re-examined and a further 5 were found to have holes develop in the fellow eye. A posterior vitreous detachment without hole formation had developed in 20 fellow eyes at 5 years. Although mean pattern reversal electroretinography and EOG responses were within normal limits in affected and fellow eyes at baseline, mean CCS protan, deutan, and tritan thresholds were elevated significantly in affected eyes at baseline (P = 0.0001). Unaffected fellow eyes showed normal mean protan and deutan thresholds, but significantly elevated mean tritan thresholds (P = 0.01) at baseline. Mean tritan CCS loss was, however, similar in fellow eyes in which holes later developed and in fellow eyes in which holes did not., Conclusions: The Kaplan-Meier estimated risk of fellow eye involvement is 15.6% (range, 8.4%-22.3%; P = 0.05) at 5 years. Although electrodiagnostic and psychophysical testing was not predictive of fellow eye involvement, tritan CCS loss at baseline, in apparently normal fellow eyes, may indicate subclinical foveal dysfunction, the nature of which is unclear.

Purpose/background: The idiopathic full-thickness macular hole (IFTMH) is an important cause of poor vision in the elderly affecting predominantly women over the age of 60 years. While it is accepted that vitreoretinal traction is an important local factor in the development of IFTMH, the underlying cause is not known. The aim of this study was to identify possible systemic risk factors for the development of IFTMH., Methods: Two hundred and thirty-seven patients with IFTMH (cases) attending the Macular Hole Clinic at Moorfields Eye Hospital were identified. These were compared with 172 patients without macular holes (controls) attending other clinics in the same hospital. Cases and controls were frequency-matched by sex. The prevalence of the following factors in both groups was ascertained by interview: ethnic origin, place of birth, housing tenure, any systemic diseases, current and lifetime consumption of medication, severe dehydrational episodes, menstrual and obstetric history, onset and severity of menopause and use of exogenous oestrogens (in women only), osteoporosis, vegetarianism, use of vitamin supplementation, and smoking and alcohol consumption. Height and weight were measured for all participants., Results: Cases of IFTMH macular holes were predominantly women (67%) and aged 65 years and older (74%). We found very few systemic risk factors that were significantly associated with IFTMH. There was a higher prevalence of diabetes in controls (12% vs 5%). There was no association between the majority of indicators of oestrogen exposure in women and macular holes, but cases had a more difficult menopause as judged by the severity of hot flushes at menopause: odds ratio 2.6 (1.4-4.6)., Conclusions: In common with other studies, we found only a few systemic factors associated with IFTMH. The study did confirm, however, that IFTMH is a strongly gender-related disease. There is some evidence for the role of sudden changes in hormonal balance, as seen by the increased reporting of severity of symptoms around the menopause along with (statistically non-significant) increased risks associated with hysterectomy and oophorectomy. The particular aetiological factor which puts women at increased risk of macular holes requires further studies.

Purpose: To investigate the role of systemic corticosteroids in the treatment of sight-threatening choroidal neovascularisation (CNV) in patients with punctate inner choroidopathy (PIC) and multifocal inner choroiditis (MIC)., Methods: Twelve eyes of 10 patients with evidence of PIC or MIC with recent visual symptoms were identified. All eyes had CNV within the foveal avascular zone on fundus fluorescein angiography (FFA). Systemic oral prednisolone at an initial dose of 1 mg/kg (60-80 mg) was given for 3-5 days and the dose was subsequently tapered. Changes in best corrected visual acuity and leakage on FFA were recorded during follow-up. Systemic side-effects of the corticosteroids were monitored., Results: In 10 of 12 eyes vision improved or stabilised. Leakage on FFA resolved in 9 eyes and was reduced in 3. Four patients required more than one course of oral corticosteroids. One patient was maintained on low-dose oral corticosteroids for recurrent CNV activity. No systemic complications from the treatment were observed., Conclusion: A course of oral corticosteroids in healthy young patients with subfoveal CNV in PIC or MIC may reduce subretinal vascular leakage and stabilise vision when no other proven treatment option is available.

Objective: To investigate the ultrastructural features of idiopathic full-thickness macular hole (FTMH) opercula excised during vitrectomy and to correlate them with the outcome of surgery., Methods: Opercula were collected from eyes undergoing vitrectomy for stage 3 FTMH using noncrushing, cupped foreign body forceps. Following immediate fixation, specimens were processed for transmission electron microscopy. The ultrastructural features were correlated with the clinical data recorded for each patient before and after surgery., Results: Eighteen specimens were studied. Native vitreous collagen was identified on the surface of all 18, while fragments of internal limiting membrane were present in 11 (61%). Eleven (61%) were found to contain only glia, comprising fibrous astrocytes and Müller cells in variable proportions. The remaining 7 (39%) were found to contain, in addition to glia, neurites and synaptic complexes, of which some were typical of cone photoreceptors. The initial surgical closure rate was significantly better in eyes in which only glia were present (9/11 [82%]), compared with those with neurites (1/7 [14%]) (P = .01). Once closure had been achieved with reoperation, the median final visual acuity was 20/60 in both groups (P = .26), although the likelihood of achieving an acuity of 20/40 or better was greater in the former (50%) than the latter group (17%)., Conclusions: Two distinct types of opercula occur in association with stage 3 FTMH--those containing only glia (pseudo-opercula), which are probably associated with a foveal dehiscence and little or no loss of foveal tissue, and those containing both glia and a significant number of avulsed foveal cones (true opercula), which arise from a full-thickness foveal tear. Although the loss of foveal tissue in true opercula would seem to explain the worse initial anatomical and more modest visual results in some eyes, significant visual improvement may still be achieved after successful closure. The presence of neurites in true opercula suggests that, in at least some cases, direct traction on the foveal retina leads to macular hole formation.

Objective: To determine the efficacy of reoperation with rigorous epiretinal membrane dissection and autologous serum for full-thickness macular holes remaining open after initial surgery., Methods: Forty-six consecutive eyes that had previously undergone unsuccessful macular hole surgery were re-treated with epiretinal membrane dissection, adjunctive autologous serum, and 16% perfluoropropane (C3F8) gas tamponade. Anatomical closure and improvement of best-corrected Snellen visual acuity were used as outcome measures, and nuclear sclerosis was graded clinically before and after reoperation., Results: Epiretinal membrane was identified and dissected in 29 (63%) of the 46 eyes and anatomical closure was achieved in 37 (80%) of the 46 eyes. Of these, 23 (62%) of 37 improved by at least 2 Snellen lines, 12 (35%) of 37 by at least 3 Snellen lines, and 6 (16%) of 37 by at least 4 Snellen lines. Increase in nuclear sclerosis occurred in 30 (65%) of the 46 eyes postoperatively, leading to cataract extraction in 12 (26%) of the eyes at last follow-up (mean, 10.3 months). A longer total duration (P<.001) and a worse preoperative visual acuity (P=.001), prior to reoperation, were associated with a worse final visual acuity after surgery., Conclusions: Retreatment with rigorous membranectomy and autologous serum seems to be beneficial in most eyes in which initial macular hole surgery has failed. Although the anatomical closure rate is similar to that reported after primary surgery, final visual acuity improvement seems to be less than after successful primary closure, owing to the longer mean duration of holes in which initial surgery has failed.

Background: Removal of silicone oil following successful retinal detachment surgery is usually performed in an attempt to prevent the complications of silicone oil; however, removal of the oil may result in retinal redetachment., Purpose: The purpose of this study was to determine whether argon laser retinopexy, 3-6 weeks prior to the removal of silicone oil, reduces the rate of retinal detachment following silicone oil removal., Methods: A total of 31 eyes of 31 consecutive patients were followed up for a 12 month period after the removal of silicone oil. All patients had undergone retinal reattachment surgery resulting in a clinically attached retina with the absence of residual retinal traction prior to silicone oil removal. A study group of 15 of the 31 eyes received two rows of 360 degrees of peripheral argon laser retinopexy 3-6 weeks before removal of the silicone oil. The 16 eyes of the previous 16 consecutive patients, who underwent removal of silicone oil without argon laser retinopexy, were used as a control group., Results: In the study group 1 of 15 eyes (6.7%) redetached following the removal of silicone oil and 4 of 16 (25%) redetached in the control group during the 12 month follow-up period from operation., Conclusions: Prophylactic argon laser retinopexy applied 3-6 weeks before the removal of silicone oil appears to reduce the retinal redetachment rate. A larger prospective randomised trial is needed to confirm these findings.

Background: Although peripapillary subretinal neovascular membranes (PSRNs) are less common and often larger than neovascular complexes arising near the fovea, they may lead to severe visual loss. Very large (massive) PSRNs (MPSRNs) are 3.5 disc areas or greater in overall size, are even less common, and may contain a significant occult component, leading to slow and unpredictable growth. Such massive lesions may begin at the nasal margin of the disc and do not become symptomatic until they have extended around the disc toward the macula, threatening central vision. Although complete laser ablation has been used for symptomatic PSRNs with variable success, the optimal treatment of MPSRNs remains controversial., Methods: The authors reviewed the clinical course of 12 eyes of seven patients with MPSRNs. Ten eyes received laser treatment, which was limited to the temporal portion of the subretinal neovascular complexes only and two received no treatment., Results: Of the ten eyes receiving laser treatment, six showed stabilization of visual acuity, whereas in four the neovascular membrane progressed beneath the fovea with severe visual loss. In the two untreated eyes, the subretinal neovascular membrane progressed beneath the macula with the loss of central vision., Conclusions: In contrast to the small symptomatic PSRNs, which are usually treated by complete laser ablation, MPSRNs may stabilize with only partial laser treatment. However, both types of lesions may remain stable for long periods of time without any treatment and require treatment only if progression toward the fovea occurs.

Aim: To describe the phenomenon of peripheral field loss following routine pars plana vitrectomy for stage 2 and 3 full thickness macular hole and to investigate the underlying mechanism., Methods: Five patients, who reported peripheral field defects after apparently uncomplicated vitrectomy, posterior cortical vitreous peeling, and perfluoropropane (C3F8) gas tamponade, were studied retrospectively with slit-lamp biomicroscopy, automated and kinetic perimetry, fundal fluorescein angiography, focal electroretinography (ERG), and colour contrast sensitivity (CCS) testing., Results: All five patients, who were between 50 and 73 years of age, reported an inferotemporal field defect following resolution of the intraocular gas bubble. In all eyes, the scotomata encroached to within 20 degrees to 30 degrees of fixation and to within 5 degrees to 15 degrees of the blind spot. In one eye, a partial altitudinal component was evident. All scotomata subsequently remained stable and three eyes developed subtle segmental nasal disc pallor and nerve fibre loss corresponding to the field defect. CCS testing revealed absent colour contrast in the scotomatous area, in the presence of a preserved focal quadrantic flash ERG, compared with normal CCS protan thresholds and focal ERGs in unaffected quadrants, indicating preserved outer retinal function in the area of the scotoma., Conclusions: These observations support the hypothesis that field defects occur as a result of retinal nerve fibre layer damage. It is proposed, on the basis of intraoperative observations and other evidence, that the most likely site of nerve fibre damage is at the nasal portion of the optic nerve rim or peripapillary retina, probably due to traction during cortical vitreous peeling.

Background: Vascular endothelial growth factor (VEGF) has been shown to play a major role in intraocular neovascularisation in ischaemic retinal diseases. Subretinal neovascularisation is an important cause of central visual loss, but little is known about the role of this growth factor in its pathogenesis. The aim of this study was to investigate the possible role of VEGF in the development of subretinal neovascularisation., Methods: Undiluted vitreous samples were obtained from patients undergoing vitrectomy for removal of non-age-related subfoveal neovascular membranes (SFNM). For comparison vitreous from patients undergoing vitrectomy for idiopathic full thickness macular holes (FTMH) and proliferative diabetic retinopathy (PDR) was used. Indirect enzyme linked immunosorbent assay (ELISA), with an antibody directed against the conserved N-terminal region of human VEGF165, was used to determine vitreous levels of VEGF. The growth factor was also localised in the vitreous of patients with SFNM by western blot analysis., Results: The mean (SE) VEGF concentration in the vitreous of patients with SFNM was 27.78 (2.22) ng/ml (n = 8), FTMH was 16.62 (0.9) ng/ml (n = 18), and PDR was 37.77 (3.28) ng/ml (n = 16). The differences between the PDR group and SFNM group versus the FTMH group were both significant (p = 0.0001 and p = 0.0015) as analysed by the Wilcoxon rank sum test)., Conclusions: Vitreous levels of VEGF are significantly elevated in eyes with non-age-related subretinal neovascularisation compared with eyes with FTMH but not as elevated as in PDR. This suggests that VEGF is involved in subretinal angiogenesis.

Introduction: In the late stages of proliferative diabetic retinopathy (PDR) the vascularized posterior cortical gel (PCG) contracts leading to a partial posterior hyaloidal separation, hemorrhage, and traction retinal detachment (TRD). "Additional epiretinal membranes" have been described previously. These are thin, usually transparent epiretinal membranes which extend anteriorly from the point of attachment of the elevated posterior cortical gel to the edge of the TRD. The origin and frequency of the occurrence as well as the clinical significance of such additional epiretinal membranes are the subjects of controversy., Purpose: To quantitate the authors' clinical impression that additional epiretinal membranes are common in advanced PDR, to characterize them immunohistochemically, and to demonstrate the rationale for the authors' surgical approach., Methods: Intraoperative observations for all patients undergoing diabetic vitrectomy and delamination over the last 2 years were reviewed retrospectively. The presence of additional epiretinal membrane was searched for in the initial stages of vitrectomy. When identified, their apparent continuity with the elevated portion of the PCG was confirmed. Surgical specimens were obtained from nine patients for immunohistochemical study., Results: Additional epiretinal membranes were observes in 145 (81%) of 179 consecutive eyes with PDR that underwent surgery for macular TRD. Immunohistochemical staining with type II collagen antibody was positive in all specimens, suggesting that these membranes were of vitreous origin., Conclusions: It is likely that the additional epiretinal membranes represent the posterior leaf of a split PCG, the anterior leaf being the elevated portion of the PCG. The two leaves remain fused in the main, fibrovascular portion of the epiretinal membrane. These findings help explain the clinical experience that once the posterior leaf of the PCG is identified and elevated, it provides an accurate point of entry into the surgical plane facilitating delamination of the fused (vascularized) portion of the PCG from the detached retina.

We report on a new method of subretinal fluid drainage which uses the indirect ophthalmoscopic delivery of argon laser energy to perforate the choroid. This carries all the theoretical advantages of drainage with the endolaser probe but is simpler and less expensive. We present a prospective series of 31 patients in whom this method was applied. Satisfactory drainage was obtained in 28. There were 4 cases of limited subretinal haemorrhage attributable to the laser, and 1 case of subfoveal haemorrhage. No cases of retinal perforation or incarceration were observed.

Background: Full-thickness macular holes (FTMH) are an important cause of visual loss in older patients. Recognition of tangential vitreofoveal traction as the mechanism of hole formation has led to the use of vitrectomy and gas tamponade as a treatment for macular holes. The use of growth factors as an adjunctive therapy to promote chorioretinal adhesion and hole closure has also been advocated., Methods: Forty-four consecutive patients undergoing vitrectomy, posterior hyaloid removal, gas injection and installation of autologous serum for FTMH were studied prospectively. Patients' age, sex, duration of symptoms, best corrected pre- and post-operative Snellen visual acuities, best corrected acuity in the fellow eye, stage of macular hole, post-operative closure or persistence of the macular hole, and intra- and post-operative complications were recorded., Results: Of 43 patients with adequate follow-up (minimum 6 weeks, mean 6.1 months) anatomical closure of the macular hole was achieved in 29 eyes (67%). The average visual improvement in these eyes was 2.7 lines. Twenty eyes (69%) with closed holes had visual acuity of 6/12 or better (47% of all patients undergoing surgery). Of the 14 eyes (33%) that failed, the average loss of vision was 0.4 lines and all these eyes had vision of 6/36 or worse., Conclusions: In this series, surgical treatment of FTMH with vitrectomy, gas injection and autologous serum resulted in closure of the macular hole in two-thirds of patients and restored central vision in about one-half of patients. These results compare favourably with previously reported results of macular hole surgery. The answer to the question whether the use of autologous serum leads to a higher closure rate than surgery with gas tamponade alone requires information from randomised treatment trials, one of which is currently in progress.

Background: Idiopathic full-thickness macular holes (FTMH) are an important cause of loss of central vision in the elderly. Improved understanding of the natural history and pathophysiology of FTMH has led to recent advances in the surgical management of patients with this hitherto untreatable condition., Methods: The current concepts of the natural history and surgical treatment are reviewed. Pilot studies of vitrectomy undertaken to relieve the tangential traction at the vitreomacular interface and the role of growth factors as promoters of a limited healing response are reviewed and illustrated by the results of surgical treatment of macular holes obtained by the author and others., Results: Whereas early pilot studies of vitrectomy of impending (stage I) macular hole suggested beneficial results (80-95% of operated eyes did not progress to FTMH), no such benefit could be demonstrated by a subsequent randomised treatment trial. In a study of early vitrectomy and partial fluid-gas exchange hole closure was achieved in 88% of patients with stage II FTMH with visual improvement in 67%. In other studies of FTMH (stages II-IV) the addition of adjunctive substances such as growth factors, autologous serum, plasma or platelet concentrate has resulted in closure in 77-100% of cases. However, similar results have also been reported with vitrectomy and gas tamponade alone. Histologically the closure of the FTMH is associated with glial proliferation., Conclusion: Vitrectomy and intraocular tamponade appear to be beneficial in patients with FTMH. The role of adjunctive substances, such as growth factors and other promoters of the healing response, requires clarification by randomised treatment trials.

Few retinal detachments have been described in patients with retinitis pigmentosa and allied retinal disorders, with only two cases (both with hearing loss) reported in association with giant retinal tears. To further characterise clinical characteristics of giant retinal tear associated with retinitis pigmentosa, we reviewed the course of four eyes of three patients. Unexpectedly, all three individuals also suffered from congenital sensorineural hearing loss. One suffered from associated myopathy. Despite aggressive surgical management, three of the four eyes became blind. The diagnosis of retinal detachment preceded the diagnosis of photoreceptor dystrophy in two of the three patients. To date, giant retinal tears occurring with underlying retinitis pigmentosa have been described in five young individuals, all of whom had associated congenital sensorineural hearing loss.