Management of repository corticotropin injection therapy for non-infectious uveitis: a Delphi study.

PURPOSE: Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases. METHODS: The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). RESULTS: The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent. CONCLUSIONS: Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.

Crystalline Maculopathy Secondary to Retinal Tear Without Detachment.

Purpose: Crystalline maculopathy secondary to chronic retinal detachment (RD) has previously been described. This article proposes a novel mechanism to explain crystalline formation in the absence of RD. Methods: Two patients, who were referred for routine examination, were found to have a crystalline maculopathy in the setting of an asymptomatic, chronic-appearing, peripheral retinal tear. Fundoscopy and optical coherence tomography were used to assess the crystals and tear. No specimens were obtained. Results: We describe 2 cases of a crystalline maculopathy secondary to an asymptomatic peripheral retinal tear. We hypothesized macrophage ingestion of photoreceptor segments emanating from the tear may have contributed to macular crystalline deposition. Conclusions: Because crystalline maculopathy can present in the setting of RD, there may be a shared pathogenesis between the 2 conditions.

Bullous Variant of Central Serous Chorioretinopathy: Expansion of Phenotypic Features Using Multimethod Imaging.

PURPOSE: To define the phenotypic characteristics of the bullous variant of central serous chorioretinopathy (CSC) using multimethod imaging. DESIGN: Retrospective, observational case series. PARTICIPANTS: Twenty-one eyes of 14 patients with bullous retinal detachment resulting from CSC (bullous CSC group) and 122 eyes of 84 patients with chronic CSC without bullous retinal detachment (nonbullous CSC group). METHODS: We performed a retrospective review of clinical and multimethod imaging data of patients who sought treatment from the authors with bullous retinal detachment resulting from CSC between January 2010 and November 2015. Multimethod imaging comprised color photography, fluorescein angiography, fundus autofluorescence, and high-resolution optical coherence tomography. Consecutive cases of chronic CSC without bullous retinal detachment, seen during the same period, comprised a comparative group. MAIN OUTCOME MEASURES: Qualitative and quantitative characteristics of the choroid, retinal pigment epithelium, and retina were compared between the 2 groups. RESULTS: Mean age of the bullous CSC group was 53.8 years. There was no difference in age, visual acuity, corticosteroid use, or the proportion of white patients and men between the 2 groups (all P > 0.132). Peripheral nonperfusion occurred only in eyes with bullous retinal detachment (38% of cases). Retinal pigment epithelial tears were seen in 95% of eyes in the bullous group and none of the eyes in the nonbullous CSC group. The bullous CSC group demonstrated a greater number of pigment epithelial detachments (PEDs) and more eyes demonstrated PEDs with internal hyperreflectivity (both P < 0.016). Mean subfoveal choroidal thickness in the bullous CSC group (463.1±83.1 µm) was not different compared with that of the nonbullous CSC group (400.6±100.6 µm; P = 0.993). More eyes in the bullous CSC group demonstrated hyperreflectivity around large choroidal vessels and at the level of the choriocapillaris on OCT (P < 0.001). Retinal folds and subretinal fibrin were identified in a greater proportion of eyes in the bullous CSC group (both P < 0.001). CONCLUSIONS: Bullous retinal detachment is a rare manifestation of chronic CSC and is characterized by a unique constellation of phenotypic and multimethod imaging features.

Punctate inner choroidopathy and optic neuropathy: simultaneous presentation in a patient - a case report.

BACKGROUND: We present a case of a patient initially presenting with multifocal choroiditis (MFC) in one eye. She subsequently developed lesions most consistent with punctate inner choroidopathy (PIC) in the contralateral eye, followed by acute vision loss from retrobulbar optic neuropathy. Optic neuropathy has been well described in the setting of MFC. There is, however, only one report of its association with PIC. Punctate inner choroidopathy and MFC have many similarities, with visual loss generally resulting from choroidal neovascularization. In this case, the patient had significant visual loss from presumed retrobulbar optic neuropathy. FINDINGS: The patient responded well to immunomodulation with subsequent return of vision to baseline. CONCLUSIONS: Multifocal choroiditis and punctate inner choroidopathy may be a spectrum of the same disease with many overlapping presentations, including optic neuropathy. Good visual recovery and remission were attained with mycophenolate mofetil and systemic corticosteroid treatment.

Pars plana vitrectomy, fluocinolone acetonide implantation, and silicone oil infusion for the treatment of chronic, refractory uveitic hypotony.

PURPOSE: To assess the feasibility and outcomes of combining fluocinolone acetonide sustained drug delivery implant insertion, pars plana vitrectomy, and silicone oil infusion to treat patients with chronic, refractory ocular hypotony resulting from uveitis. DESIGN: Retrospective chart review. METHODS: A retrospective, institutional chart review was performed. Outcome measures included visual acuity, intraocular pressure, and adverse events. RESULTS: A total of 13 eyes of 11 patients were studied. All patients were women, had a mean age of 57 years (range, 26 to 73 years), and had a diagnosis of panuveitis. The mean duration of preoperative hypotony was 42 months (range, 11 to 108 months). Patients were followed up on average for 22 months (range, 9 to 46 months) after the combined surgical procedure. The mean preoperative visual acuity was 20/1000 (logarithm of the minimal angle of resolution, 1.7). At the 6- and 12-month visits, the mean visual acuity remained stable at 20/800 (logarithm of the minimal angle of resolution, 1.6; P = .74) and 20/600 (P = .34), respectively. At baseline, the mean intraocular pressure (IOP) was 2.3 mm Hg. The average IOP was 5.9 mm Hg, 5.1 mm Hg, and 5.0 mm Hg at 6, 12, and 24 months after surgery, respectively. The increase in IOP relative to the baseline IOP was statistically significant at 6 and 12 months (P = .027 and P = .004, respectively). The duration of preoperative hypotony inversely correlated with the IOP at 6 months (P = .027). No intraoperative complications were encountered and the procedure was well tolerated. CONCLUSIONS: Fluocinolone acetonide implantation combined with pars plana vitrectomy and silicone oil infusion is feasible and is well tolerated in the management of chronic, refractory ocular hypotony associated with uveitis.

Surgical outcome of scleral buckling compared with scleral buckling with vitrectomy for treatment of macula-off retinal detachment.

BACKGROUND AND OBJECTIVE: To compare the surgical outcome of scleral buckling (group 1) versus scleral buckling with pars plana vitrectomy (group 2) for the repair of macula-off rhegmatogenous retinal detachment without proliferative vitreoretinopathy. PATIENTS AND METHODS: A retrospective chart review was performed. RESULTS: Eighty-three patients were identified in group 1 and 63 patients in group 2. Presenting visual acuity was 4/200 in group 1 and 3/200 in group 2. Median duration of detachment prior to surgery was 5 days in group 1 and 6 days in group 2. There was no statistical difference in best-corrected (P = .59) or most recent (P = .75) visual acuity between groups. Median best-corrected visual acuity was 20/30 and median most recent visual acuity was 20/40 in both groups. Significantly more additional procedures were performed in group 1 than in group 2 (21.7% vs 7.9%, respectively; P = .024). The final reattachment rate was 96.4% in group 1 and 98.4% in group 2. Proliferative vitreoretinopathy developed in 15.7% of patients in group 1 and 4.8% in group 2 (P= .037). CONCLUSION: Visual outcome of scleral buckling is similar to scleral buckling with pars plana vitrectomy for the treatment of macula-off rhegmatogenous retinal detachment in patients without proliferative vitreoretinopathy. Patients undergoing scleral buckling only are at an increased risk of developing proliferative vitreoretinopathy and requiring additional procedures.

Intraoperative use of handheld spectral domain optical coherence tomography imaging in macular surgery.

PURPOSE: To describe the intraoperative use of handheld spectral domain optical coherence tomography (SDOCT) imaging in macular surgery. DESIGN: Prospective, observational case series. METHODS: A handheld SDOCT device was used to obtain preincision optical coherence tomography imaging in patients undergoing vitrectomy for macular diseases. After removal of the internal limiting membrane or the epiretinal membrane, repeat intraoperative imaging was obtained. Spectral domain optical coherence tomography findings were characterized. RESULTS: An efficient technique was established for obtaining intraoperative SDOCT imaging. A total of eight patients were included in the study. Four patients underwent surgery for macular hole, three patients for epiretinal membrane, and one for vitreomacular traction. Comparison of the preincision and intraoperative SDOCT images demonstrated distinct changes in retinal contour and macular hole configuration. Intraoperative SDOCT imaging identified additional membranes in two patients. CONCLUSION: The intraoperative use of handheld SDOCT imaging provides an efficient method for visualizing macular pathology. This technology may, in certain cases, help confirm or identify diseases that may be difficult to visualize during surgery.

Hepatic metastasis from uveal melanoma: angiographic pattern predictive of survival after hepatic arterial chemoembolization.

OBJECTIVE: To identify clinical features associated with survival after hepatic arterial chemoembolization (HACE) for uveal melanoma metastasis. METHODS: Retrospective case series including 11 men and 10 women with uveal melanoma metastasis. RESULTS: The hepatic angiographic pattern of metastasis was infiltrative in 12 patients (57%) and nodular in 9 patients (43%). The infiltrative pattern was associated with ciliary body involvement by the primary tumor (Fisher exact test, P = .01) and extrascleral tumor extension (Fisher exact test, P = .01). Mean survival after the first HACE treatment was 7.6 months overall, 3.7 months for the patients with the infiltrative pattern, and 12.7 months for those with the nodular pattern. This difference was highly significant (Kaplan-Meier, P < .001). Chromosome 8p was found to be deleted in 4 patients with the infiltrative pattern and in no patients with the nodular pattern. CONCLUSIONS: The hepatic metastasis pattern can be used to predict response to and survival after HACE. Loss of chromosome 8p may be a biomarker for the infiltrative metastasis pattern. Hepatic arterial chemoembolization may play an important role in the treatment of hepatic metastasis from uveal melanoma in patients with the nodular metastatic pattern. Regular screening for hepatic metastasis in patients with uveal melanoma may be beneficial in identifying those who would benefit from HACE.

Hepatic arterial chemoembolization for management of metastatic melanoma.

OBJECTIVE: Hepatic arterial chemoembolization is an accepted therapy for stage 4 melanoma with liver-dominant metastasis. However, the reports of outcomes are limited. We present our outcomes with hepatic arterial chemoembolization for metastasis of stage 4 melanoma. MATERIALS AND METHODS: Twenty patients with liver-dominant metastasis of ocular or cutaneous melanoma were treated with hepatic arterial chemoembolization. Overall survival and progression-free survival rates were calculated from the first treatment. Patients with intrahepatic tumor progression were treated with additional hepatic arterial chemoembolization. Both overall survival and progression-free survival were analyzed with the Kaplan-Meier method. Tumor pattern on angiography was characterized as either nodular or infiltrative on the basis of angiographic appearance. RESULTS: The 20 patients underwent 46 hepatic arterial chemoembolization sessions (mean, 2.4 sessions; range, 1-5). The mean and median overall survival times were 334 +/- 71 and 271 days, respectively. There were no deaths within 30 days of treatment. Thirteen of the 20 patients had progression of disease. The mean and median progression-free survival times for these patients were 231 +/- 42 and 185 days, respectively. Patients with lesions that had a nodular angiographic appearance had longer progression-free survival than patients with lesions that had an infiltrative appearance (mean progression-free survival time, 249 vs 63 days). Patients with lesions that had a nodular angiographic appearance also survived significantly longer than those with lesions that had an infiltrative angiographic pattern (mean overall survival time, 621 vs 114 days; p = 0.0002). CONCLUSION: Hepatic arterial chemoembolization for liver-dominant metastasis of stage 4 melanoma is a safe treatment that results in longer survival than has occurred among historical controls. Patients with lesions that have a nodular tumor appearance on angiography survive significantly longer than patients with lesions that have an infiltrative appearance on angiography.

Safety of intravitreal injections in patients receiving warfarin anticoagulation.

PURPOSE: To evaluate the safety of intravitreal Macugen (OSI/Eyetech, New York, New York, USA) injections among patients receiving warfarin anticoagulation. DESIGN: Retrospective chart review. METHODS: A search was conducted for patients treated with intravitreal Macugen for choroidal neovascularization resulting from age-related macular degeneration (AMD). Inclusion criteria included patients receiving warfarin anticoagulation in whom therapy was maintained. RESULTS: The review identified 31 patients (32 eyes) who underwent 102 intravitreal Macugen injections while receiving warfarin anticoagulation. The mean and median number of Macugen injections per patient was three. No intraoperative or immediate postoperative hemorrhagic complications were noted. One patient experienced an acute submacular hemorrhage 35 days after the third Macugen injection. There were no other hemorrhagic events among the remaining patients. CONCLUSIONS: The retrospective chart review of patients treated with intravitreal Macugen for choroidal neovascularization resulting from AMD while receiving warfarin therapy suggests that patients may undergo intravitreal injections safely without cessation of anticoagulation therapy.

Maintenance of warfarin anticoagulation for patients undergoing vitreoretinal surgery.

OBJECTIVE: To evaluate the risk of hemorrhagic complications associated with vitreoretinal surgery in patients whose warfarin sodium therapy was continued throughout the surgical period. METHODS: A review of 1737 records of patients undergoing pars plana vitrectomy was conducted. Inclusion criteria included patients receiving warfarin therapy whose international normalized ratios (INRs) were elevated above normal values on the day of surgery. Intraoperative and postoperative hemorrhagic complications were documented. RESULTS: Fifty-four patients underwent 57 vitreoretinal surgical procedures with warfarin therapy and were divided into groups as follows: group S with INRs of 1.20 to 1.49, values considered subtherapeutic; group B with INRs of 1.50 to 1.99, values considered borderline therapeutic; group T with INRs of 2.00 to 2.49, values considered therapeutic; and group HT with INRs of 2.50 or greater, values considered highly therapeutic. No patients experienced anesthesia-related or intraoperative hemorrhagic complications. Two (7.7%) of 26 eyes in group S and 2 (16.7%) of 12 eyes in group HT experienced postoperative hemorrhages. All of the patients with vitreous hemorrhages had spontaneous clearing without additional treatment. CONCLUSIONS: Many patients may safely undergo vitreoretinal surgery while maintaining therapeutic levels of warfarin anticoagulation. We experienced no intraoperative hemorrhagic complications; the 4 postoperative complications resolved spontaneously without persistent visual sequelae or the need for supplemental surgery.

Maintenance of warfarin anticoagulation for patients undergoing vitreoretinal surgery.

PURPOSE: The purpose of this study was to evaluate the risk of hemorrhagic complications associated with vitreoretinal surgery in patients in whom warfarin therapy was continued throughout the surgical period. METHODS: A review of 1,737 consecutive charts of patients undergoing pars plana vitrectomy was conducted. Inclusion criteria included patients on warfarin therapy whose international normalized ratio (INR) was elevated above normal on the day of vitreoretinal surgery. The occurrence of intraoperative and postoperative hemorrhagic complications was documented. RESULTS: The retrospective review detected 54 patients who underwent 57 vitreoretinal surgical procedures while on warfarin therapy. Group S consisted of patients whose INR ranged from 1.2 to 1.49, values that were considered to be subtherapeutic. Group B had INR values ranging from 1.5 to 1.99, values that were considered to be borderline therapeutic. Group T had INRs ranging from 2.0 to 2.49, values that were considered therapeutic. Group HT had INRs of 2.5 or greater, values that were considered highly therapeutic. No patients experienced anesthesia-related or intraoperative hemorrhagic complications. Four procedures (7.0%) were complicated by postoperative hemorrhage. Two of 26 eyes (7.7%) in group S and two of 12 eyes (16.7%) in group HT experienced postoperative hemorrhages. All hemorrhagic complications cleared without additional therapy. CONCLUSIONS: Our findings suggest that many patients may safely undergo vitreoretinal surgery while maintaining therapeutic levels of warfarin anticoagulation. We found no intraoperative hemorrhagic complications. Those hemorrhagic complications that occurred postoperatively resolved spontaneously without persistent visual sequelae or the need for supplemental surgery.

Desferoxamine (DFO)--mediated iron chelation: rationale for a novel approach to therapy for brain cancer.

Iron homeostasis is crucial to normal cell metabolism, and its deficiency or excess is associated with numerous disease states. The association of increased iron load with cancer may be due to several factors including free radical production, reduction of the body's protective mechanism to combat oxidative stress, inhibition of immune systems, inhibition of essential nutrient functions, facilitation of cancer growth, suppression of antitumor actions of macrophages, and lowering of the ratio of T4-T8 positive lymphocytes. Antiproliferative effects of desferoxamine (DFO) both in vitro and in vivo are mediated by an intracellular pool of iron that is necessary for DNA synthesis rather than prevention of iron uptake from transferrin. Several clinical studies have shown it to have antitumor activity in the treatment of neuroblastoma, leukemia, bladder carcinoma, and hepatocellular carcinoma. Human neural tumor cells are susceptible to the effects of DFO. Continued study of DFO is necessary to further elucidate its antineoplastic profile and its use as an adjunct to current chemotherapy regimens. Given the lack of satisfactory treatment of central nervous system neoplasms, DFO could serve as an important tool in the management of such cancers.