Barbara Iaccheri

A Pilot Study on Ocular Safety of Intravitreal Infliximab in a Rabbit Model

PURPOSE To determine whether infliximab may be used safely as an intraocular drug, the ocular safety of intravitreal infliximab in rabbits was studied by clinical examination, electroretinography (ERG), and histology in rabbits. METHODS Twelve New Zealand albino rabbits were selected for this study. Different infliximab doses, namely 1.0 mg, 1.7 mg, and 3.3 mg in 0.1 mL, were injected intravitreally into one eye each of three rabbits. As a control, the vehicle solution was injected into the fellow eye of each animal. Eye clinical examination and ERG recordings were made before and 2, 6, and 12 weeks after injection. Eventually, the rabbits were humanely killed, and the retinas were examined by light microscopy. In addition, the elimination half-life of the drug in the vitreous was assessed. RESULTS Slit lamp biomicroscopy, indirect funduscopy, and ERG evidenced no significant differences between control and infliximab-injected eyes in this rabbit model, at any of the tested doses. Histologic examination revealed no retinal abnormality in the rabbits injected with 1 mg and 1.7 mg intravitreal infliximab. In two of three eyes injected with 3.3 mg infliximab, significant edema of the nerve fibers was detected compared with the control group. The half-life of the drug was estimated to be 8.5 days. CONCLUSIONS These results indicate that infliximab may be a safe intravitreal drug in the rabbit model at a dose of up to 1.7 mg. If proven safe and efficacious in further studies, intravitreal injection of infliximab could be considered an alternative to systemic administration in selected patients.

Macular Thickness Measured by Optical Coherence Tomography in a Healthy Population Before and After Uncomplicated Cataract Phacoemulsification Surgery

Purpose: To examine macular changes before and after uncomplicated cataract surgery in a healthy population. Material and Methods: In a prospective study, we evaluated 62 eyes of healthy patients having elective cataract phacoemulsification. We performed optical coherence tomography (OCT) measurements preoperatively and at 3, 6, 12, 20, and 28 weeks after surgery. The retinal map was divided into minimal foveal thickness, a central 1-mm disk area, and two peripheral ring areas with diameters of 3 mm and 6 mm, respectively, and centered on the fovea. We compared the postoperative OCT values against the respective preoperative values. Results: Two eyes (3.2%) developed cystoid macular edema (CME) after cataract surgery and were excluded from the study. With respect to preoperative values, visual acuity improved significantly postoperatively, and at 12 weeks, we observed an asymptomatic increase in retinal thickness at 3 mm and 6 mm. Macular volume showed a statistically significant increase at the 12th week after surgery. There was no correlation between macular changes and best corrected visual acuity (BCVA) or ultrasound time. Conclusions: Our data indicate that the onset of clinically significant CME is rare after uncomplicated phacoemulsification cataract surgery, but with respect to preoperative values we observed an asymptomatic increase in macular thickness and volume at 12 weeks. The possible onset of macular alterations after uncomplicated cataract surgery must be taken into account as a potential later complication, because it can lead to a permanent loss of visual acuity.

Rituximab Treatment for Persistent Scleritis Associated with Rheumatoid Arthritis

Purpose: To report a clinical case of a patient with severe scleritis associated with rheumatoid arthritis (RA) refractive to conventional treatment that was treated effectively with rituximab. Methods and Results: A 55-year-old man with RA, on etanercept and oral methotrexate, was referred with diagnosis of acute stromal keratitis, anterior uveitis, and anterior nodular scleritis in his right eye. Cyclophosphamide induced complete regression of acute stromal keratitis and anterior uveitis, but scleritis was still active and persistent. After two 1000-mg infusions of rituximab, scleritis regressed completely and is still in remission 9 months after the second rituximab infusion, without any concomitant use of oral steroids. Conclusion: Rituximab may be a treatment alternative in severe scleritis that is refractive to conventional therapy. Considering its safety profile, further studies are needed to refine its mechanism of action, optimal indications, and dosing in ocular inflammation.

Acute Posterior Multifocal Placoid Pigment Epitheliopathy: Outcome and Visual Prognosis

Objectives: To examine the clinical outcomes and the effect of treatment in patients with acute posterior multifocal placoid pigment epitheliopathy. Methods: Cases of acute posterior multifocal placoid pigment epitheliopathy treated at the Massachusetts Eye and Ear Infirmary from 1990 to 2002 and cases from the literature were identified. Data on visual acuity, ocular symptoms, bilateral involvement, foveal involvement at presentation, and treatment regimens were recorded. Results: Visual acuity was 20/25 or worse in 226 (76.6%) eyes and 20/40 or worse in 172 (58.3%) eyes at presentation. At the last follow-up visit, visual acuity was 20/25 or less in 125 (42.3%) eyes and 20/40 or less in 70 (23.7%) eyes. Topical or systemic therapy was given in nearly half of the cases (54.4%). Overall, 87 (71.9%) eyes were symptomatic at last follow-up visit. Finally, measured visual acuity was more than 20/25 in 20 (87.5%) eyes without foveal involvement at presentation and in 28 (39.2%) eyes with foveal involvement. Conclusions: Although acute posterior multifocal placoid pigment epitheliopathy shows a relatively benign prognosis, especially when compared with some of the other white dot syndromes, there are patients who experience incomplete visual recovery.

Somatostatin for Uveitic Cystoid Macular Edema (CME)

Purpose: To report the favorable response of bilateral recalcitrant uveitic cystoid macular edema (CME) to treatment with a somatostatin analog. Methods: Medical ophthalmic history and the results of ophthalmic examinations were recorded. Fluorescein angiography (FA) studies were reviewed. Results: A 52-year-old white female with intermediate uveitis developed bilateral recalcitrant CME. Treatment with subcutaneous injections of the somatostatin analog octreotide resulted in partial resolution of the CME and improvement of visual acuity. Conclusions: Somatostatin may play a role in the treatment of CME secondary to uveitis.

Adverse drug reactions to treatments for ocular toxoplasmosis: A retrospective chart review

OBJECTIVE This study evaluated the incidence and types of adverse drug reactions (ADRs) associated with medications used to treat active toxoplasmic chorioretinitis. METHODS This was a retrospective review of the clinical records of a consecutive series of patients with active toxoplasmic chorioretinitis, examined between March 1991 and August 1998. For inclusion in the review, patients had to have been diagnosed with active toxoplasmic chorioretinitis, been treated with a single drug or drug combination indicated for this condition, and been followed for at least 8 weeks. Patients who were lost to follow-up or who had incomplete chart data were excluded. Demographic data, pertinent aspects of the medical history, drug treatments, and ADRs associated with antitoxoplasmic treatment were recorded. RESULTS Fifty-five patients met the criteria for inclusion in the review. In descending order of frequency, they received antitoxoplasmic treatment with clindamycin (n = 50), sulfadiazine (n = 40), pyrimethamine (n = 33), trimethoprim-sulfamethoxazole (n = 16), and atovaquone (n = 10), alone or in combination. Twenty-two patients (40.0%) had a total of 27 ADRs. The most frequently occurring ADRs were rash (19 [34.5%]), mostly associated with sulfadiazine (9/40 [22.5%]) and clindamycin (6/50 [12.0%]), and gastrointestinal ADRs such as diarrhea (6 [10.9%]), stomach upset (6 [10.9%]), and bleeding (1 [1.8%]), mostly associated with clindamycin (5/50 [10.0%], 3/50 [6.0%], and 1/50 [2.0%], respectively). The incidence of ADRs associated with individual antitoxoplasmic drugs was 30.0% (3/10) for atovaquone, 26.0% (13/50) for clindamycin, 22.5% (9/40) for sulfadiazine, 12.5% (2/16) for trimethoprim-sulfamethoxazole, and 12.1% (4/33) for pyrimethamine. There were 2 serious ADRs: gastrointestinal bleeding in a patient treated with clindamycin and leukopenia in a patient treated with pyrimethamine. Twenty-five ADRs were reversed on drug discontinuation; the remaining 2 were mild and did not require drug discontinuation. CONCLUSIONS The overall incidence of treatment-associated ADRs was high (40.0%) in these patients with ocular toxoplasmosis. The most frequently occurring ADRs were rash and gastrointestinal complaints.

Repeatability and Reproducibility of Retinal Thickness Measurements in Diabetic Patients with Spectral Domain Optical Coherence Tomography

ABSTRACT Background: To determine the repeatability and reproducibility of optical coherence tomography (OCT) Spectralis retinal thickness measurements in diabetic patients with clinically significant macular edema (CSME). Methods: Twelve eyes of 12 volunteers (without macular pathology – control group) and 21 eyes of 21 diabetic patients with CSME were included in the study. Reproducibility, repeatability, intraclass correlation coefficients (ICCs) and intrasession correlation coefficients were tested with 20 × 15 degree raster scans consisting of 19 high-resolution line scans that were repeated three times by two experienced examiners. Results: In the control group, examining all regions, coefficient of repeatability was less than 1.1%, while coefficient of reproducibility was less than 2.2%. In diabetic patients, examining all regions, coefficient of repeatability was less than 2.6%, while coefficient of reproducibility was less than 2.4%. ICCs were, respectively, greater than or equal to 0.98 in the control group and 0.99 in diabetic patients. Intrasession coefficients of variation were less than 0.4% in the control group and less than 0.5% in diabetic patients. Conclusion: Retinal thickness measurements are repeatable and reproducible with OCT Spectralis in both the control group and diabetic patients. The results indicate that a change in central subfield thickness exceeding 12 µm and 3% in the diabetic patients is likely to be real.

Outcomes of early and late immunomodulatory treatment in patients with HLA-B27-associated chronic uveitis.

PurposeTo evaluate the outcomes of early versus late immunomodulatory treatment (IMT) in patients with HLA-B27-associated chronic uveitis.MethodsSeventy-two patients (114 eyes) with HLA-B27-associated chronic uveitis received IMT at the Ocular Immunology & Uveitis Service of the Massachusetts Eye and Ear Infirmary and were evaluated retrospectively. Main outcome measures were visual acuity, control of inflammation, number of flare-ups and steroid-sparing effect.ResultsThe median time between diagnosis and start of IMT was 3.05 years. Accordingly, patients were divided into two groups: group A comprised those in whom initiation of IMT was within the first 3 years (36 patients), and in group B initiation of IMT was more than 3 years from the initial diagnosis (36 patients). Control of inflammation was achieved in 29 patients (80.5%) of the early-treated group and in 33 patients (91.6%) of the late-treated group. A steroid-sparing effect was achieved for 13 (81.25%) of the 16 and for 11 (73.33%) of the 15 patients who were on systemic steroid in the early- and late-treated groups respectively. The mean follow-up for the early-treated group was 2.14 years and for the late-treated group, 3.46 years.ConclusionsImmunomodulatory therapy is an effective treatment for severe HLA-B27 uveitis that fails to respond to conventional steroid treatment, regardless of the timing of its initiation. However, introduction of IMT within 3 years of the disease onset prevents the adverse effects of steroids (cataract, glaucoma) and reduces the likelihood of repeated recurrences of the uveitis.

Safety and efficacy of small incision, sutureless pars plana vitrectomy for patients with posterior segment complications secondary to uveitis

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Bilateral chronic anterior uveitis & neuro-ophthalmologic manifestations in a patient with Churg-Strauss syndrome: an unusual ocular presentation.

We describe a patient with Churg-Strauss syndrome (CSS) who developed bilateral chronic anterior uveitis and neuroophthalmologic manifestations 20 years after the onset of asthma and sinus disease. The patient was treated successfully with a combination of cyclophosphamide and prednisone, after other immunomodulatory strategies, aside from systemic prednisone, had failed.