Carlos Pavesio

Evaluation of an Intravitreal Fluocinolone Acetonide Implant versus Standard Systemic Therapy in Noninfectious Posterior Uveitis

PURPOSE To evaluate the safety and efficacy of an intravitreal fluocinolone acetonide (FA) implant compared with standard therapy in subjects with noninfectious posterior uveitis (NIPU). DESIGN Randomized, controlled, phase 2b/3, open-label, multicenter superiority trial. PARTICIPANTS Subjects with unilateral or bilateral NIPU. METHODS One hundred forty subjects received either a 0.59-mg FA intravitreal implant (n = 66) or standard of care (SOC; n = 74) with either systemic prednisolone or equivalent corticosteroid as monotherapy (> or =0.2 mg/kg daily) or, if judged necessary by the investigator, combination therapy with an immunosuppressive agent plus a lower dose of prednisolone or equivalent corticosteroid (> or =0.1 mg/kg daily). MAIN OUTCOME MEASURES Time to first recurrence of uveitis. RESULTS Eyes that received the FA intravitreal implant experienced delayed onset of observed recurrence of uveitis (P<0.01) and a lower rate of recurrence of uveitis (18.2% vs. 63.5%; P< or =0.01) compared with SOC study eyes. Adverse events frequently observed in implanted eyes included elevated intraocular pressure (IOP) requiring IOP-lowering surgery (occurring in 21.2% of implanted eyes) and cataracts requiring extraction (occurring in 87.8% of phakic implanted eyes). No treatment-related nonocular adverse events were observed in the implant group, whereas such events occurred in 25.7% of subjects in the SOC group. CONCLUSIONS The FA intravitreal implant provided better control of inflammation in patients with uveitis compared with systemic therapy. Intraocular pressure and lens clarity of implanted eyes need close monitoring in patients receiving the FA intravitreal implant.

Electrophysiological characterisation and monitoring in the management of birdshot chorioretinopathy

Aims: To characterise patients with birdshot chorioretinopathy (BCR) clinically and electrophysiologically in order to monitor changes in retinal function before and after treatment with corticosteroids and/or immunosuppression. Methods: 18 patients with BCR were characterised clinically and electrophysiologically. Serial studies were performed on 14 patients in order to monitor changes in retinal function before and after treatment with corticosteroids and/or immunosuppression. Results: Most patients presented with characteristic subretinal pale spots, were HLA-A29 positive, and had diverse signs of ocular inflammation. Various electrophysiological abnormalities were present. Moderately severe bilateral pattern electroretinogram (PERG) abnormalities at presentation were common, reflecting macular dysfunction. Cone mediated 30 Hz flicker electroretinograms (ERGs) were consistently delayed before treatment, and were the most sensitive parameter of retinal dysfunction. Scotopic maximal ERG responses were abnormal in 13 patients; 10 had an electronegative maximal ERG or a reduced b:a ratio in one or both eyes. Single flash photopic ERGs were less often and less severely affected. Photopic ON and OFF ERG responses often revealed predominant ON response b-wave abnormalities with relative OFF response preservation. ERGs improved in treated cases, sometimes preceding clinical signs of recovery. Pattern ERG improvements occurred, possibly reflecting the resolution of macular oedema. Conclusions: The ERG data confirm that BCR frequently affects inner retinal function of cone and rod systems. Clinical features were not reliable indicators of functional deterioration or recovery. Objective electrophysiological assessment of retinal function demonstrated improvement following treatment and provides a reliable method of monitoring treatment efficacy, enabling management decisions to be taken with greater confidence and allowing early initiation or modification of treatment.

The natural history and management of recurrent corneal erosion: a prospective randomised trial

One hundred and seventeen patients with a history of recurrent corneal erosion were recruited at initial hospital presentation. Seventy-five cases had a history of shallow corneal injury, 23 had epithelial basement membrane dystrophy (EBMD), 8 had both and 11 had neither. Mean age at presentation was 38 years and follow-up ranged from 6 to 16 months (mean 10.6 months). Sixty-one patients presented with a first acute corneal erosion, 21 with a subsequent acute corneal erosion and 35 with chronic symptoms. Patients with EBMD or a trauma-related focal epithelial basement membrane abnormality were more likely to present with chronic recurrent symptoms than trauma-related cases with no abnormality on examination. Both EBMD and trauma-related cases typically recurred in the lower half of the cornea, frequently in the midline (z = 7.3, p < 0.0001), suggesting an intrinsic or acquired abnormality of the epithelial basement membrane at this site. Only four of 82 acute episodes did not resolve by 5 days with simple patching, cycloplegia and topical antibiotic ointment. In the vast majority of patients presenting with an acute erosion, simple management measures only are required. Of 117 cases started on prophylactic ointment at night, further therapy due to prophylaxis failure was required in only 5. EBMD was a risk factor for failure (relative risk 10.77). There was no difference in efficacy between once daily prophylactic paraffin and hypertonic saline ointments (p = 0.17), suggesting they both have only a lubricant action.

Treatment of ocular inflammatory conditions with loteprednol etabonate

Ocular inflammatory diseases impose a significant medical and economic burden on society. Corticosteroids are potent anti-inflammatory agents that have been used successfully to treat ocular inflammation. Topical corticosteroids provide maximal drug delivery, and are used to reduce the signs and symptoms of intraocular and ocular surface inflammation. However, side effects associated with topical corticosteroids—including increased intraocular pressure, risk of cataract formation after long-term use, and decreased resistance to infection—are concerns. Loteprednol etabonate (LE) is an ester corticosteroid with a high therapeutic index that contains an ester, rather than a ketone, at carbon-20 of the prednisolone core structure. LE blocks the release and action of inflammatory mediators and is clinically effective in the treatment of steroid-responsive inflammatory conditions including giant papillary conjunctivitis, seasonal (intermittent) allergic conjunctivitis and uveitis. LE relieves ocular surface and lacrimal gland inflammation associated with dry eye and is used in combination with ciclosporin A as a treatment of dry eye. LE is also effective in the treatment of postoperative ocular inflammation. Because of its rapid de-esterification to inactive metabolites, LE appears to have an improved safety profile compared with ketone corticosteroids, and may be more suitable than ketone corticosteroids for the treatment for ocular inflammatory conditions in which long-term therapy is necessary. However, further comparative safety studies are needed.

Acute Retinal Necrosis: The Effects of Intravitreal Foscarnet and Virus Type on Outcome

PURPOSE To study the effects of intravitreal foscarnet and the clinical differences between varicella zoster virus (VZV) and herpes simplex virus (HSV) induced acute retinal necrosis (ARN). DESIGN Retrospective comparative case series. PARTICIPANTS Eighty-one eyes of 74 patients. METHODS A retrospective case note analysis was performed in 2 tertiary referral centers. MAIN OUTCOME MEASURES Presenting and final visual acuity, and progression to retinal detachment. RESULTS Thirty-three eyes had HSV-ARN and 48 had VZV-ARN. The average age for HSV-ARN was 34 years and 51 for VZV-ARN (P<0.001). Visual acuity on presentation was similar (P = 0.48), but a larger proportion had better vision (> or =20/60) in the HSV-ARN group (52%) than the VZV-ARN group (35%). A greater proportion of eyes with poor vision (< or =20/200) was found at the 12-month follow-up in the VZV-ARN group (60%) compared with the HSV-ARN group (35%). A greater degree of visual loss in the VZV-ARN group (0.4 logarithm of the minimum angle of resolution [logMAR]) compared with the HSV-ARN group (0.04 logMAR) was detected (P = 0.016). Retinal detachment was 2.5-fold more common in VZV-ARN (62%) compared with HSV-ARN (24%). When comparing eyes treated with (n = 56) and without (n = 25) intravitreal foscarnet, there was a 40% lower rate in retinal detachment (53.6% vs 75.0%) for VZV-ARN (P = 0.23). The numbers with HSV-ARN were too small for analysis. CONCLUSIONS The results support the difference of outcome in HSV-ARN and VZV-ARN. Therefore, viral identification serves as a key to predicting outcome in these patients. Intravitreal foscarnet seems to be a useful adjunct for the treatment of ARN in that it reduced rate of retinal detachment.

The effect of pars plana vitrectomy on cystoid macular oedema associated with chronic uveitis: a randomised, controlled pilot study

Aim: To evaluate the efficacy of pars plana vitrectomy (PPV) in the management of chronic uveitic cystoid macular oedema (CMO). Methods: A prospective, interventional, randomised, controlled, pilot study. 23 eyes of 23 patients with CMO secondary to chronic intermediate or posterior uveitis unresponsive to medical treatment were randomised into a surgical (group S) or medical group (group M). 12 patients in group S underwent PPV as opposed to 11 patients in group M who received systemic corticosteroid and/or immunosuppressive treatment during the study period. The primary outcome measures of the study were change in visual acuity and angiographic appearance of CMO at 6 months. Results: Mean visual acuity in group S improved significantly from 1.0 (0.62) at baseline to 0.55 (0.29) at 6 months following vitrectomy (p = 0.011), with five (42%) eyes reaching vision of 20/40 or better. Conversely, mean visual acuity in group M improved only marginally by 0.03 (0.27) (p = 0.785). CMO after vitrectomy was angiographically improved in four (33%) eyes, remained unchanged in seven (58%) eyes, and deteriorated in one (8%) eye. In the medical group, fluorescein leakage decreased in one eye, did not alter in four eyes, and deteriorated in two eyes. Conclusion: PPV for macular oedema secondary to chronic uveitis despite angiographic improvement in only one third of the patients, seems to have a significant beneficial effect on visual function. This study provides enough evidence to justify a large scale trial which would define the role of vitrectomy in uveitic macular oedema.

Paraneoplastic syndromes associated with visual loss.

Purpose of review The recent literature was reviewed to analyze the developments in the diagnosis, pathogenesis, and immunology of this group of paraneoplastic syndromes. Clinical features and pathologic findings are summarized. Recent findings The mechanism of cell death in cancer-associated retinopathy appears to occur through apoptotic pathways. Caspase inhibitors and a calcium antagonist have been used in animal models to block or suppress the effect of the antirecoverin antibodies on the retina with significant response. These agents are possible treatment options for cancer-associated retinopathy. Aberrant expression of recoverin by tumor cells does not necessarily induce antirecoverin antibodies and cancer-associated retinopathy. Many tumors, not just those producing the clinical picture of cancer-associated retinopathy, have been shown to express recoverin. Recoverin appears to play a functional role in tumor cells, and antirecoverin antibodies may have tumor-suppressing effects. Further research into this area may help design epitope-based immunotherapy for patients with recoverin-expressing tumors. Further evidence has emerged to support the initial observation that depolarizing bipolar cells are the likely retinal target in melanoma-associated retinopathy. Intravitreal injection of melanoma-associated retinopathy serum produced electroretinogram changes in animals very similar to the clinical findings in humans. Many new antibodies and antigens had been discovered to be linked to various paraneoplastic syndromes. Anti-collapsing response-mediating protein-5 is likely to be an important one; it was found to be the second most common autoantibody related to paraneoplastic neurologic syndromes. Summary Further research into the functional role of recoverin in cancer cells may advance our understanding in cancer immunology. Immunotherapy may be possible if a specific epitope of recoverin can be found to contain the antigenic site for antitumor antibodies and not cross-react with retinal antigens. Research into the pathogenesis of the other paraneoplastic syndromes is required for a better understanding and treatment of these rare conditions. The missing link between primary cutaneous melanoma and uveal melanocytes still eludes investigators in bilateral diffuse uveal melanocytic proliferation. The discovery of the missing link may provide us with some understanding of the development of uveal melanoma.

Acanthamoeba sclerokeratitis: Treatment with systemic immunosuppression

OBJECTIVE This study describes the clinical features, management, and outcome of 19 patients who had severe Acanthamoeba sclerokeratitis (ASK) unresponsive to conventional management, requiring systemic immunosuppression to control disease. DESIGN Retrospective, non-comparative, interventional case series. PARTICIPANTS Records of all patients with Acanthamoeba keratitis treated at Moorfields Eye Hospital between 1989 and 2000 were reviewed. From more than 200 patients, 19 who developed ASK treated with systemic immunosuppression were identified. MAIN OUTCOME MEASURES Visual acuity, level of pain, and degree of inflammation were recorded after immunosuppressive treatment. RESULTS ASK requiring immunosuppression occurred in 20 eyes of 19 patients (11 males and 8 females). The mean age (mean +/- standard deviation) at onset was 38.6 +/- 13.2 years. On presentation, best-corrected visual acuity was counting fingers or worse in 11 eyes (55%), 6/18 to 6/60 in 5 eyes (25%), and 6/12 or better in 4 eyes (20%). The mean time between onset of initial symptoms of Acanthamoeba keratitis and commencement of systemic immunosuppression was 4.8 +/- 3.5 months. The mean duration of immunosuppression required to control inflammation was 7.2 +/- 3.9 months. Severe scleritic pain remained uncontrolled in two patients and resulted in enucleation. Best-corrected visual acuity at final follow-up was counting fingers or worse in eight eyes (40%), 6/18 to 6/60 in six eyes (30%), and 20/40 or better in six eyes (30%). The mean follow-up period after resolution of inflammation was 24.3 +/- 20.9 months (range, 0.2-59.7 months). CONCLUSIONS ASK is an uncommon complication of Acanthamoeba keratitis. The scleritis associated with this infection seems to be an immune-mediated response. After topical amebicidal treatment, systemic immunosuppression may be required to control the pain and tissue destruction associated with ASK.

Systemic disorders associated with episcleritis and scleritis.

Inflammation of the episclera and sclera still represents a diagnostic challenge. Many of these presentations are idiopathic and are managed empirically with the use of anti-inflammatory therapy, usually with a satisfactory response. However, some cases will have a more aggressive nature or will show resistance to conventional therapy, and those potentially are connected to an infectious or underlying disease. In such cases, there is an increased risk of visual loss and severe systemic complications requiring intensive investigations and aggressive therapy. The diseases more commonly associated with these conditions, especially with scleritis, are the connective tissue disorders and systemic vasculitis, but systemic infections and malignancies also must be excluded. Management depends on the specific diagnosis, and every year a new list of potential associations or atypical presentations is reported. For a successful outcome, it is important that these presentations are recognized.

Vitreous surgery in the management of chronic endogenous posterior uveitis

AbstractObjectives There is evidence that pars plana vitrectomy (PPV) has a beneficial effect on the clinical course of chronic endogenous posterior uveitis (EPU) possibly by physically removing any resident inflammatory cells with the vitreous. We assessed the anatomical and therapeutic effects of PPV performed on patients with chronic EPU for any indication.Patients and methods Retrospective review of 41 eyes of 38 consecutive patients with EPU who underwent a PPV for any reason, over a 5-year period. The mean age of the patients was 36.2 years, 46% of the eyes had intermediate uveitis, 32% panuveitis, and 22% posterior uveitis. The visual acuity, disease activity, and the requirement for medications to control it were recorded for 12 months pre- and postoperatively.Results Overall, 61% of the eyes gained more than 2 Snellen lines (P<0.001) and the incidence of cystoid macular oedema (CMO) significantly reduced from 44 to 20% (P<0.05). Postoperatively, there was a significant decrease in the recurrence rate of intermediate uveitis, posterior uveitis, and panuveitis (P<0.001). The use of systemic and local depot immunosuppressive agents did not change over the study period, although the use of topical agents increased (P<0.05).Conclusion PPV appears to have a beneficial effect on the clinical course of EPU in selected cases. This may be mediated by the physical clearance of inflammatory debris, the anti-inflammatory effect of replacing vitreous by aqueous humour, by a reduction of CMO and/or the anatomical correction of sight-threatening retinal pathology.