Cataract progression in macular hole cases: results with vitrectomy or with observation.

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.

Intraocular oxygen distribution in advanced proliferative diabetic retinopathy.

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.

Macular edema--rationale for therapy.

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.

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

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

Direct comparison of enoxaparin and nadroparin in a rabbit model of arterial thrombosis prevention.

INTRODUCTION: The aim of the study was to evaluate and compare the efficacy of standard unfractionated heparin (UFH) and low-molecular weight heparins (LMWH's). MATERIALS AND METHODS: We modified a previously published rabbit model of arterial thrombosis prevention [1,2] to compare unfractionated heparin and two different doses of two low-molecular weight heparin fragments--nadroparin and enoxaparin. Thrombosis in the distal aorta was triggered by vessel wall injury and critical stenosis. Blood flow in the damaged arterial segment was monitored by a flow probe placed distal to the constrictor. The primary endpoints of the study were: (1) cumulative flow, (2) time to occlusion and (3) residual clot weight. Thirty six animals were split into 6 groups with six animals in each group. Control groups were given saline or heparin and four more groups were used to compare LMWH's at 2 different doses. RESULTS: In our study, all treatments were superior to the saline control group (alpha

Ultrastructure and retinal imaging of epiretinal membrane: a clinicopathologic correlation of trypan blue staining in epiretinal membrane surgery.

PURPOSE: The purpose of this study was to correlate the ultrastructural morphology of epiretinal tissue with optical coherence tomography and to investigate the effects of trypan blue staining on epiretinal membrane (ERM) ultrastructure and clinical outcome. METHODS: A prospective, case-comparative study. Consecutive patients were recruited and underwent vitrectomy and ERM peeling with 0.15% trypan blue; these patients were compared with a control group peeled without stain. Optical coherence tomography was performed preoperatively and at 10 days and 3 months postoperatively. Data were collected prospectively to include Snellen visual acuity and surgical ERM characteristics. Epiretinal tissue was examined using transmission electron microscopy. RESULTS: Thirty-seven patients underwent ERM surgery, and 34 had complete data, of which 18 had peeling of unstained and 16 had peeling of stained ERM. Staining resulted in a significantly greater postoperative reduction in macular thickness compared with the unstained group. There was no significant difference in the visual outcome and no ultrastructural evidence of alteration of the cleavage plane in cases in which trypan blue was used. CONCLUSION: There was no clinical or ultrastructural evidence of toxicity in peeling with trypan blue.

Ultrastructure and retinal imaging of internal limiting membrane: a clinicopathologic correlation of trypan blue stain in macular hole surgery.

PURPOSE: The purpose of this study was to correlate the ultrastructural morphology of epiretinal and retinal tissue with optical coherence tomography assessment and to investigate the effects of trypan blue staining on internal limiting membrane (ILM) tissue. METHODS: This was a prospective case-comparative study. Consecutive patients were recruited and underwent ILM peel with 0.5 mL of 0.15% trypan blue, and these were compared with a nonrandomized control group (unstained ILM). Patients underwent optical coherence tomography scanning preoperatively and postoperatively at 1.5 and 3 months. Data were collected prospectively to include Snellen visual acuity, macular hole, and operative characteristics. Internal limiting membrane was examined by transmission electron microscopy. RESULTS: Sixty-four patients underwent macular hole surgery, and complete data were available on 49 patients (17 control subjects and 32 patients who had peeling of stained ILM). Trypan blue staining significantly improved ease and completeness of ILM removal. There was no significant difference in vision, optical coherence tomography characteristics, or macular hole closure rate at 3 months between stained and unstained groups. There was no ultrastructural evidence of alteration of the plane of ILM separation in cases in which trypan blue was used. CONCLUSION: Trypan blue stain from these data seems to improve the ease and completeness of the ILM peeling (assessed clinically) and does not show any signs of toxicity.

Vitreoretinal complications of osteoodontokeratoprosthesis surgery.

PURPOSE: To describe the vitreoretinal complications in a cohort of patients with osteoodontokeratoprosthesis (OOKP) and discuss surgical management. METHODS: Review of notes of 35 OOKP cases performed at the Sussex Eye Hospital (Brighton, United Kingdom) between January 1999 and December 2005 was performed. RESULTS: The overall incidence of vitreoretinal complications was 22.8%, which included vitreous hemorrhage (3 patients), rhegmatogenous retinal detachment (3 patients), endophthalmitis with retinal detachment complicating lamina resorption and optic extrusion (2 patients), and intraoperative choroidal hemorrhage (1 patient). Preexisting aphakia was associated with rhegmatogenous retinal detachment (P < 0.05, chi2 = 4.36). Five patients required pars plana vitrectomy, which was performed either endoscopically (two cases) or using a binocular indirect viewing system (three cases) with one case requiring removal of the OOKP and insertion of a temporary keratoprosthesis. Retinal detachment repair was attempted on four of five patients but was successful for only one. Vitreous hemorrhage without retinal detachment required vitrectomy in one case, while two cases cleared spontaneously. CONCLUSIONS: Eyes receiving OOKP are prone to vitreoretinal complications, with retinal detachment associated with a poor prognosis. Thicker OOKP laminae and lamina bulk screening will hopefully reduce the risk of endophthalmitis due to unexpected resorption.

A prospective study of binocular visual function before and after successful surgery to remove a unilateral epiretinal membrane.

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.

Posterior hyaloid changes following intravitreal triamcinolone and macular laser for diffuse diabetic macular edema.

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.

Nature of subretinal fluid in patients undergoing vitrectomy for macular hole: a cytopathological and optical coherence tomography study.

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.

Hughes syndrome.

Antiphospholipid syndrome, also known as Hughes syndrome, is a recently described entity that mimics symptoms of other diseases such as multiple sclerosis. It is a potentially life-threatening autoimmune disorder where the body produces antibodies directed against phospholipids and phospholipid-binding proteins. Herein a patient with successive ocular vascular events associated with antiphospholipid syndrome is presented.

Pars plana vitrectomy with and without peeling of the inner limiting membrane for diabetic macular edema.

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.

Vitreous and aqueous concentrations of proangiogenic, antiangiogenic factors and other cytokines in diabetic retinopathy patients with macular edema: Implications for structural differences in macular profiles.

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.

Sudden visual loss after removal of silicone oil.

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.

Vitrectomy for a persisting macular fold in a case of resolved hypotony maculopathy.

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.

Surgery for idiopathic full-thickness macular hole: two-year results of a randomized clinical trial comparing natural history, vitrectomy, and vitrectomy plus autologous serum: Morfields Macular Hole Study Group RAeport no. 1.

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.