Ocular Relapse Research Articles

Management of primary intraocular lymphoma (PIOL): Results from the prospective German PIOL registry (PIOL-R).

2054 Background: Primary intraocular lymphoma (PIOL) is a very rare disorder, and the optimal treatment is yet to be defined. Here, we report clinical characteristics and outcome of patients with PIOL enrolled in the prospective German PIOL registry (PIOL-R). Methods: Patient data in this prospective, non-interventional multicenter study were compiled by standardized questionnaires sent to Ophthalmology and Hematology/Oncology centers in Germany. All histologically or cytologically confirmed immunocompetent PIOL patients were eligible. Results: Fifteen patients (8 female, median age 66 years, median Karnofsky performance status 90%) from 4 centers were included between August 2008 and January 2012. Median follow-up was 7 months. Median time from first occurrence of symptoms to PIOL diagnosis was 5 (range, 1-11) months. All PIOL were of diffuse large B-cell histology. Eight patients had concomitant (n=3), prior (n=2) and/or subsequent (n=4) parenchymal brain involvement. First-line treatment included methotrexate (MTX)-, rituximab- and/or ifosfamide-based systemic chemotherapy in 12 (including high-dose chemotherapy [HDCT] with autologous stem cell transplantation [ASCT] in 2), intraocular (i.o.) chemotherapy with MTX (n=2) and/or rituximab (n=6) in 7, and ocular radiation in one patient(s). Two patients received prophylactic intrathecal (i.th.) treatment with MTX and none had whole-brain irradiation. The PIOL remission rate was 100% (complete remission in 11/14 evaluable patients and partial remission in 3 patients). Four patients relapsed in the brain after 5, 6, 21 and 23 months and received salvage treatment with MTX and/or ifosfamide (n=3) and HDCT with ASCT (n=1). No ocular or systemic relapses were observed. Median progression-free survival was 23 (95% confidence interval, 19-26) months. All patients are alive. Conclusions: Although the awareness of PIOL and diagnostic possibilities have improved over the past 2 decades, time from symptom presentation to diagnosis seems to remain at previously reported levels. There appears to be a shift from local ocular treatments and radiation to systemic therapy as compared to anecdotal data with promising response and survival rates.

Primary intraocular lymphoma in a patient with systemic lupus erythematosus

Dear Editor, Establishment of an intraocular lymphoma may form a diagnostic challenge, especially when biopsy is contraindicated due to the anatomic site of the lesion. In recent years, vitreous IL-10 levels above 400 pg/mL (sensitivity 80 %, specificity 99 %) and a vitreous IL-10 to IL-6 ratio greater than 1.0 (sensitivity 74 %, specificity 75 %) were found to be associated with the presence of an intraocular lymphoma [1, 2]. We present a case where retinal biopsy was not possible. A 45-year-old female with a history of lupus nephritis class V presented with panuveitis of her right eye and loss of visual acuity of both eyes. During fundoscopy, a slightly elevated lesion was observed (Fig. 1a). As there was no systemic activity of her lupus erythematosus and the patient was immunocompromised due to chronic use of azathioprine and prednisolone, opportunistic infections were considered. No Herpes Simplex Virus, Varicella Zoster Virus, Cytomegalovirus, Epstein–Barr virus, toxoplasmosis, borreliosis, syphilis, or tuberculosis were found. Vitrectomy, however, revealed a rapidly growing lesion involving the macula lutea (Fig. 1b–c). Vitreous fluid analysis showed atypical lymphocytes and an interleukin-10 to interleukin-6 ratio of 14.8 (3,700 and 250 pg/mL, respectively), indicative of lymphoma rather than a non-neoplastic cause of uveitis. Brain magnetic resonance imaging, bone marrow, and spinal fluid analysis showed no abnormalities. Histology of the primary tumor could not be obtained as biopsy of this area would result in blindness. The patient was diagnosed with a solitary intraocular lymphoma and was treated with 2 cycles of intravenous methotrexate (3 g/m2, days 1 and 15); BCNU (100 mg/m2, day 4); teniposide (100 mg/m2, days 2–3); prednisolone (60 mg/m2, days 1–5); and intrathecal methotrexate, cytarabine, and hydrocortisone (15 mg, 40 mg, and 25 mg, respectively, days 1 and 15). The visual acuity of both eyes improved during treatment, suggesting a shrinking mass in both eyes. As there were no visible lesions in the left eye, only the right eye was irradiated (30 Gy). Six months later, the patient developed a lesion consistent with an intraocular lymphoma in the left eye, and at this time, radiotherapy was initiated for the left eye. Up-to-date, almost 2 years later, fundoscopy only shows flat scars, and the patient has no signs of ocular, cerebral, or systemic relapse (Fig. 1d). Fig. 1 Fundoscopic images of the right eye of a 45-year-old female. a Uveitis and an underlying whitish, slightly elevated lesion. b Lesion after vitrectomy, 12 weeks later. c Autofluorescent image postvitrectomy. d Flat scar without signs of relapse, ... Although high IL-10 levels are not pathognomonic for an intraocular lymphoma, patients with suspect lesions in regions which are essential for vision may benefit from vitreous interleukin measurement. If, in this way, a retinal biopsy can be avoided, eyesight can be retained. Furthermore, in patients presenting with a unilateral intraocular lymphoma, irradiation of the contralateral eye should be considered as up to 80 % actually have bilateral disease [3].

Unilateral exudative retinal detachment as the sole presentation of relapsing acute lymphoblastic leukemia

Ocular findings are rarely the initial symptom of leukemia, although up to 90% of all leukemia patients have fundus changes during the course of the disease. Herein we report a relapsing acute lymphoblastic leukemia patient with thesole presentation of sudden visual loss and exudative retinal detachment. An 8-year-old boy with acute lymphoblasticleukemia developed sudden visual loss during his first remission period. Bullous retinal detachment with total afferentpupillary defect was observed. Orbital magnetic resonance imaging revealed an intraocular mass lesion; simultaneouslyobtained bone marrow and cerebrospinal fluid samples showed no evidence of leukemic cells. Following local irradiation,and systemic and intrathecal chemotherapy the mass disappeared. Local irradiation, and systemic and intrathecalchemotherapy effectively controlled the isolated ocular relapse of acute lymphoblastic leukemia and eliminated the needfor enucleation.

Long-term Efficacy and Safety of Low-Dose and Dose-Escalating Interferon Alfa-2a Therapy in Refractory Behçet Uveitis

To investigate the long-term efficacy and safety of low-dose and dose-escalating therapy of interferon alfa-2a in the treatment of Behçet uveitis. This study included 37 patients with refractory Behçet panuveitis unresponsive to conventional immunosuppressive therapy. Induction interferon alfa-2a therapy was given as a daily dose of 3.0 million IU (MIU) subcutaneously for 14 days. Maintenance dose was achieved with 3.0 MIU 3 times per week given subcutaneously. The dosage was increased sequentially to 4.5, 6.0, and 9.0 MIU 3 times per week if uveitis relapses occurred. Total therapy duration was 24 months. Primary outcome measure was control of uveitis with quiescence during maintenance therapy. Ocular relapses per patient-year before and after initiation of interferon alfa-2a therapy and a corticosteroid-sparing effect were secondary outcomes. We also estimated the rate of remission after discontinuing interferon alfa-2a therapy. During maintenance therapy, interferon alfa-2a controlled uveitis in 35 patients (95%). In 15 patients (41%), a maintenance dosage of 3.0 MIU 3 times per week controlled uveitis without any relapse. The rate of uveitis relapses decreased from 3.52 per patient-year before to 0.75 per patient-year after initiating interferon alfa-2a therapy. Seventeen patients were receiving systemic corticosteroids at the time of initiation of interferon therapy. During the maintenance stage, 9 patients were able to discontinue and 8 to taper systemic corticosteroid therapy. Survival analysis estimated that the rate of remission after discontinuation of interferon alfa-2a therapy was 76% by 3 months. The rate of remission remained stable thereafter. A treatment protocol using a low-dose and dose-escalating therapy with interferon alfa-2a was able to control and achieve remission of uveitis in most patients with refractory ocular Behçet disease.

Late relapse in primary central nervous system lymphoma: clonal persistence

Recurrence of primary central nervous system lymphoma (PCNSL) after initial diagnosis and treatment occurs within 2 years in most patients, and relapse after 5 years is rare. We evaluated late relapse in our PCNSL population. We identified 10 patients from our database of 378 patients (268 achieved a complete response and 230 had relapse) with PCNSL who had relapse ≥5 years after initial diagnosis. At initial diagnosis, their median age was 47 years; all patients had brain involvement and achieved a complete response to initial therapy (9 received high-dose methotrexate). Median time to first relapse was 7.4 years (range, 5.2-14.6 y). Eight patients had relapse in the brain, 1 had ocular relapse, and 1 had a systemic relapse. The histologic specimens at initial diagnosis and relapse were examined for clonal rearrangement in 3 patients; 1 had the identical clone at initial diagnosis and relapse 13.8 years later, and the other 2 were uninformative. All patients received salvage therapy (9 received systemic therapy and 1 received intraocular chemotherapy. Nine patients achieved a complete response to salvage therapy and 1 achieved a partial response. Four patients had relapse a second time. The median progression-free survival after first relapse was 31 months (range, 7.9-82.4). Late relapses accounted for 4% of all recurrences (10 of 230 patients) in our PCNSL population. Long-term persistence of the PCNSL clone was observed in one patient. Patients with late relapses have a good response to salvage therapy and prolonged survival.

Ocular biopsy through external needle drainage for isolated bilateral ocular relapse of childhood acute lymphoblastic leukemia.

Isolated ocular relapse of acute lymphoblastic leukemia is not commonly seen. Subretinal infiltration and exudative retinal detachment may not provide a positive vitreous biopsy for histopathologic confirmation. We present a case of a 5-year-old male patient with acute lymphoblastic leukemia in remission, who presented with bilateral subretinal leukemic infiltrates and exudative retinal detachment. An ocular biopsy through external needle drainage histopathologically confirmed an ocular relapse of acute lymphoblastic leukemia. Isolated ophthalmic relapse of acute lymphoblastic leukemia can present as bilateral exudative retinal detachment with subretinal infiltration. External needle drainage of the subretinal fluid and subretinal infiltration can increase the diagnostic yield for histopathologic confirmation of the relapse.

Ocular relapse of primary brain lymphoma in immunocompetent patient, treated with intrathecal rituximab

Primary brain lymphoma is a rare variant of extranodal non-Hodgkin's B-cell lymphoma. In >90% of cases, this is diffuse large B-cell lymphoma with CD20 expression and is confined to the brain, meninges, spinal cord, and eyes. It accounts for fewer than 7% of primary brain tumors. Its incidence has been rising in recent years in immunocompetent patients in their fifth and sixth decades. The rate of relapse after initial therapy based on high-dose methotrexate and/or total brain irradiation is high. There is no consensus for treating relapse, which ranges from retreatment with high doses of methotrexate, polychemotherapy, high doses of chemotherapy backed up by autologous stem-cell transplant to intrathecal chemotherapy, with widely differing results. Given the lack of consensus and poor results, new therapy options have appeared, including immunotherapy with rituximab. At a systemic level, alongside chemotherapy, its results are very modest and limited due to the low concentration it reaches in cerebrospinal fluid (CSF). However, its intrathecal and intraventricular use, though only isolated cases have been reported, has provided promising results.

Long-Term Disease Control in Patients with Primary Central Nervous System Lymphoma

Objectives: A pilot phase II trial was performed to evaluate response rate, response duration, overall survival, and toxicity in primary central nervous system lymphoma (PCNSL) after systemic and intraventricular chemotherapy with deferred radiotherapy.Patients and Methods: From 09/1995 to 12/2002, 65 patients with PCNSL (median age 62 years) were enrolled into a pilot/phase II study evaluating chemotherapy without radiotherapy. A high-dose methotrexate (MTX) (cycles 1,2,4,5) and cytarabine (ara-C) (cycles 3,6) based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide) was combined with intraventricular MTX, prednisolone and ara-C. Primary endpoint was time to treatment failure (TTF), secondary endpoints were response, overall survival, response duration, 5-year-survival fraction and (neuro)toxicity.Results: 34 patients were male, 31 female. Sixty-one of 65 patients were evaluable for response. Of these, 37 (61%) achieved a complete response (CR), 6 (10%) complete response/unconfirmed, and 12 (20%) progressed under therapy. Overall response rate was 71% for all patients and 86% for patients younger than 61 years. Six (9%) out of 65 patients died due to treatment-related complications. Follow-up time is 78 to 151 months in surviving patients (median 100 months). Kaplan Meier estimates for median time to treatment failure (TTF), median overall survival and median response duration are 22 months, 54 months and 37 months, respectively. For patients aged 60 years or older, the respective numbers were 7 months, 34 months and 30 months; in patients younger than 60 years, the Kaplan Meier estimate for TTF is 49 months, median overall survival and median response duration have not yet been reached. The 5-year survival fraction is 72% in patients < 60 years and 24% in older patients. Systemic toxicity was mainly hematologic. Ommaya reservoir infection occurred in 19% of the patients. At present, 17/30 (57%) of younger and 4/35 (9%) elderly patients are still alive. Only 5/30 (17%) of younger, but 19/35 (54%) of elderly patients received radiation salvage therapy at relapse. In 2/65 (3%), secondary cancers developed. In the subgroup of patients with long-term survival (n=17/30 under 61 years), 12 had an ongoing response, 1 an isolated CNS relapse (resolved by radiation), 1 an isolated ocular relapse (resolved by ocular radiation) and 3 a pure systemic relapse without CNS involvement (all resolved by systemic chemotherapy). Eleven of these 17 patients could be investigated by comprehensive neuropsychological testing, which revealed normal cognitive function in all of them.Conclusions: Primary chemotherapy based on high-dose MTX and ara-C is highly efficient in PCNSL. A substantial fraction of patients < 60 years can obviously be cured with this regimen.

Retrospective analysis of children with uveitis treated with infliximab

Tumor necrosis factor-alpha (TNF-alpha) antagonists have been successfully used in refractory cases of pediatric uveitis.(1-7) We report our experience with the monoclonal anti-TNF-alpha antibody infliximab in the treatment of uveitis in 20 children. Twenty children with noninfectious uveitis were treated with infliximab as an initial line of immunomodulatory therapy (4 children) or for uncontrolled intraocular inflammation despite aggressive immunosuppressive therapy (16 children). Intraocular inflammation was controlled in the short term in all children; resistance developed in 4 children after long-term therapy.

Treatment of Ocular Mucous Membrane Pemphigoid with Immunosuppressive Drug Therapy

To evaluate the effectiveness of immunosuppressive drug therapy in the treatment of ocular mucous membrane pemphigoid (MMP). Retrospective cohort study. Ninety-four patients with biopsy-proven ocular MMP seen at the Pemphigoid Clinic at Wilmer Eye Institute from July 1984 through November 2006. Data recorded included demographics, use and doses of immunosuppressive drugs, response to therapy, and side effects associated with drug use. Outcome measures included: (1) ocular control, defined as resolution of inflammation and cessation of cicatrization of the conjunctiva; (2) ocular remission, defined as ocular control for 3 months or more after the cessation of immunosuppressive drug therapy; and (3) ocular relapse, defined as the recurrence of ocular disease in either eye after a remission. By 1 year of treatment, 82.9% of patients had complete control of the inflammation, and of these, 86.3% achieved a remission at some point during follow-up. The incidences of ocular control, remission, and relapse were 1.03 (95% confidence interval [CI], 0.78-1.33), 0.50 (95% CI, 0.37-0.67), and 0.04 (95% CI, 0.02-0.09) events per person-years (PY), respectively. Among patients initially treated with prednisone and cyclophosphamide (n = 44), 91% of patients achieved a remission within 2 years after the initiation of immunosuppressive drug therapy. Characteristics at presentation associated with failing to achieve remission in the univariate analysis were trichiasis (relative risk [RR], 0.28; 95% CI, 0.08-097), prior eyelid surgery (RR, 0.11; 95% CI, 0.02-0.78), and esophageal involvement (RR, 0.29; 95% CI, 0.10-0.83). After adjusting for confounding, an initial treatment regimen containing cyclophosphamide and prednisone was associated with a greater likelihood of achieving ocular remission (RR, 8.53; 95% CI, 2.53-28.86; P = 0.001) when compared with other initial treatment regimens. Infections, hematuria, and anemia were the most common side effects observed in patients receiving cyclophosphamide therapy. The rate of discontinuing cyclophosphamide resulting from side effects was 0.20/PY; however, 74% of these patients still achieved remission despite early discontinuation of cyclophosphamide. In patients with ocular MMP, most achieved ocular disease control with immunosuppressive drug therapy. Treatment with cyclophosphamide and prednisone was strongly associated with the development of ocular remission. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ocular relapse in acute myeloid leukemia (M4) with normal bone marrow

A patient with the rare occurrence of ocular relapse of acute myeloid leukemia (AML) M4 while the bone marrow was normal is reported in this paper. A 47-year-old woman with AML was treated with chemotherapy and went successfully into remission. Four months later, she presented with pain, redness, and a mass over the left eye. The ocular relapse involved the subconjunctival space and anterior chamber of the left eye and, presumably, the left lacrimal gland. There were also multiple subcutaneous nodules on both of her forearms. Incisional biopsy from the subconjunctival lesion was performed. Histopathological examination of the specimen showed diffuse blast cell infiltration. Her bone marrow was still in remission. Although exceedingly rare, ocular extramedullary relapse in AML M4 heralds bone marrow recurrence and, despite intensive chemotherapy, the prognosis is dismal.

Vogt-Koyanagi-Harada Disease after Head Trauma

To report two cases of Vogt-Koyanagi-Harada disease after closed head trauma. Case report. Two patients, one male and one female, developed headache, dysacusis, vertigo, tinnitus, and hair hypersensitivity shortly after a closed head trauma and, 10 and 18 days later, a bilateral uveitis with papillitis and exudative retinal detachment in one and a bilateral mild uveitis with macular exudative detachment in the other. The ocular lesions resolved with intravenous high-dose steroid therapy, but recurred after reduction of the dosages, requiring further steroid therapy. The course of the disease in both patients, with the appearance of fundus depigmentation and pigment clumping, and the occurrence of a concomitant ocular and auditory relapse in one, were typical of Vogt-Koyanagi-Harada disease. Vogt-Koyanagi-Harada disease may appear after a closed head trauma suggesting that even an indirect trauma in melanocyte-containing tissue may induce an inflammatory response within the eye.

Ifosfamide or trofosfamide for intraocular lymphoma: Long-term results of a prospective study

18524 Background: The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has not yet been defined. In a prospective study, ifosfamide (IFO) or trofosfamide (TRO) have been assessed for treating IOL. Here, long-term results are presented. Patients and Methods: Patients with histologically proven isolated IOL were included. The median age of the patients was 74 years (range 46–83 years); 4 patients had a newly diagnosed disease and 6 a relapse. IFO was administered intravenously at a dose of 1.5 - 2.0 g/m2/day for 3 days every three weeks. TRO was given at a dose of 150 or 400 mg/day (continuous or intermittent administration) to 4 patients considered unable to receive intensive intravenous hydration. IFO, TRO and their active 4-hydroxy (4-OH) metabolites were measured in aqueous humor of 9 patients. Results: The median number of IFO courses was 6 (range 2–8), the median duration of TRO therapy was 8.5 months (range 6–18 months). All patients responded. Toxicity &gt; WHO grade 2 was: anemia grade 2 in 2 patients, leukopenia grade 2–3 in 2 patients, nausea/vomiting grade 2 in 2 patients, thrombopenia and cystitis grade 2 in 1 patient each. Thus far, three patients each have developed cerebral and ocular relapse. Median progression-free survival from the study treatment was 9.5 months (range 6 - 24+ months), median overall survival was 15.5 months (range 6–34 months). Both patients retreated with IFO on ocular relapse responded. In 6 of 6 patients, 4-OH metabolites were detected in the aqueous humor immediately after IFO infusion with an aqueous/serum ratio of 0.19–0.54. Three to 16 hours after ingestion of TRO, 4-OH metabolites could be detected in one of 3 patients. Conclusions: Response rate of IOL to IFO or TRO is high with a tolerable toxicity even in elderly patients. However, long-term remissions are infrequent. Combining IFO/TRO with other cytostatics seems reasonable to improve long-term disease control. No significant financial relationships to disclose.

Infliximab Treatment for Ocular and Extraocular Manifestations of Behçet's Disease

To assess the efficacy and safety of infliximab in the treatment of sight-threatening uveitis and extraocular manifestations in patients with Behçet's disease. Twelve patients with Behçet's disease and uveitis were treated with infliximab after unsuccessful therapy with other immunosuppressive drugs. The main outcome measures were as follows: the number of uveitis relapses, the number of Behçet's disease-related extraocular lesions, and the amount of corticosteroids administered during the treatment as well as during an equal prior period of time while the patients were on other immunosuppressive agents. Visual acuity was recorded at the beginning of infliximab therapy and at the end of follow-up, and was defined as stable if it did not change from baseline, increased if it showed at least one line of improvement from baseline, and decreased if it showed at least a one line decrease from baseline. During an average follow-up of 16.67 +/- 7.63 months (median, 15 months), 11 patients (91.6%) showed a reduction in the number of ocular relapses (relapse/month, from 0.35 +/- 0.17 to 0.12 +/- 0.17, P < 0.001). All of the patients (n = 11) who were taking corticosteroids before infliximab were able to reduce the amount of corticosteroids taken daily during infliximab treatment (from 24.33 +/- 10.84 mg/prednisone per day to 8.97 +/- 6.81 mg/prednisone per day, P < 0.001), and all presented with a reduced onset of extraocular manifestations of Behçet's disease (mean total number, from 2.83 +/- 3.61 to 1.51 +/- 2.35, P = 0.039). One patient, who had to stop treatment 2 months after starting because of the onset of pulmonary tuberculosis, showed the same number of relapses during infliximab treatment but was able to reduce the mean daily corticosteroid dose. Visual acuity increased by one or more lines in three eyes (12.5%) and remained unchanged in 87.5% of the eyes. Infliximab-related side effects appeared in four patients (33.3%). Infliximab was effective in the treatment of uveitis in these Behçet's disease patients, significantly reducing the number of ocular relapses and making possible a significant reduction in the daily dose of corticosteroids administered. Extraocular manifestations of Behçet's disease were also controlled by infliximab. Nevertheless, side effects were not uncommon, and an extensive study of systemic conditions before infliximab administration had to be carried out to exclude systemic infection, particularly prior tuberculosis.

Anti-TNF therapy in the management of Behcet's disease--review and basis for recommendations

Summary and conclusions The published evidence on the use of anti-TNF agents in BDconsists mainly of reports of the open use of infliximab,principally evaluated as an add-on therapy. The majority ofpatients suffered from relapsing, posterior segment ocularinflammation, inadequately controlled with available immuno-suppressive therapy. With infliximab, a fast-onset therapeuticeffect was repeatedly observed in patients with sight-threateninginflammation, including patients with retinal vasculitis. Thepaucity of effective and fast-acting therapies particularly forpatients with eye disease underscores the importance of thesefindings. As suggested by three independent, open-label, prospec-tive, self-controlled studies, repetitive infliximab infusions werealso effective in preventing ocular relapses, maintaining visualacuity and tapering immunosuppressive therapy in the majority ofpatients who had an inadequate response or were intolerant toconventional therapy. Infliximab was effective for extra-ocularmanifestations in these patients, as well as in other patients withrecalcitrant orogenital ulcers, arthritis, intestinal or centralnervous system involvement and in a single patient withpulmonary artery aneurysm. With short-term use, there were noserious side effects reported. The only randomized controlled trialwas a 4-week study of etanercept in patients with mucocutaneousmanifestations. Etanercept was beneficial for most of thesemanifestations, but no data are at hand from this study on eyeinvolvement.Anti-TNF agents have a number of disadvantages, includinginduction of potentially serious adverse events and high cost.However, based on the available evidence, physicians may decideto provide anti-TNF therapy to patients with definite BD.However, until results from adequately powered, randomizedcontrolled clinical trials are available, TNF blocking agentsshould be used with caution only for selected patients withsevere disease. Patients with two or more relapses of posterioruveitis per year, low visual acuity due to chronic cystoid macularoedema, or active CNS disease and/or selected patients withintestinal inflammation, or arthritic and mucocutaneous manifes-tations that reduce significantly the quality of life, would fit thiscategory. According to the experience accumulated so far,infliximab seems to be more efficacious than etanercept in diseasemanifestations other than mucocutaneous or joint involvement,while data on adalimumab are very limited. Infliximab oretanercept is recommended as an add-on therapy for selectedpatients with BD, who are refractory or intolerant to traditionalimmunosuppressive regimens. Moreover, a single infusion ofinfliximab (5mg/kg), can be used as a first-line agent for sight-threatening, bilateral posterior eye segment inflammation, whenthe fast-onset of response is considered to be critical to preventfixed retinal lesions and thus permanent visual loss. In those caseswhose ocular relapses are not controlled by azathioprine and/orciclosporin, a maintenance therapy with infliximab at the dose of5mg/kg every 6–8 weeks could be used for up to 2 years, providedno relapses occur between intervals. These recommendations donot constitute treatment guidelines but are intended to improvepractice uniformity and to help physicians in the management ofBD patients, until higher grades of evidence are available.

Proton beam therapy for iris melanomas

To describe the results in terms of local control, eye preservation and systemic evolution of iris melanomas treated by proton beam irradiation. Retrospective review of the charts of patients with iris melanoma treated by proton beam therapy between April 1998 and September 2002. Ciliary body melanomas with iris involvement or tumours with extrascleral invasion were excluded. Treatment consisted of 60 Gy of proton beam irradiation delivered in four fractions to the tumour volume. A total of 21 patients were treated, median follow-up of 33 months (8-72 months). 15 patients presented a lesion with documented growth. The median clinical diameter was 5 mm (2-8 mm), the median ultrasound diameter 4.8 mm (2-7.7 mm) The patients were 6% T1, 57.1% T2, and 14.3% T3 all N0M0. The iridocorneal angle was invaded by the tumour in 71.4% of patients. At the end of follow-up, all patients were alive with no proven metastatic disease except one patient with suspicious liver lesions. None of the patients showed tumour progression or ocular relapse. The tumour response at 2 years was a flat lesion for 6.3% of cases, partial regression in 75% and stable in 18.8%. None of the patients required secondary enucleation. The main complication was cataract (45% within 24 months of treatment). Raised intraocular pressure was observed in 15% of patients but no neovascular glaucoma. Proton beam therapy shows potential utility for selected cases of localised iris melanomas allowing excellent local tumour control and eye preservation. Further follow-up on larger series is needed to confirm these results.

Primary intraocular lymphoma (PIOL): An International Primary CNS Lymphoma Collaborative group report

1534 Background: PIOL is a hemopoietic tumor that arises in the retina, vitreous or optic nerve head, and carries a high risk of ocular and CNS relapse. The natural history and optimal management are unknown. Methods: A retrospective series of 81 patients with PIOL was assembled from 15 centers in 7 countries. Only patients with isolated ocular lymphoma were included; none had brain, spinal cord, or systemic lymphoma at diagnosis. Results: The median age at diagnosis was 65 (24–85). 58% were women. The median ECOG performance status was 0, and only three had a score &gt; 1. The median latency from symptom onset to diagnosis was 6 months (0– 36). Slit lamp exam was positive in 51, negative in 6, and not reported in 24. Vitrectomy was positive in 72 and negative in 2. 6 had a positive choroidal or retinal biopsy and 1 had no ocular surgery. CSF cytology was positive in 10 (17%), negative in 48, and unknown in 23. 21 received local therapy at diagnosis: 6 intra-ocular methotrexate (400 ug), 14 ocular radiation (median 3600 cGy), and 1 both modalities. 52 received more extensive therapy including systemic chemotherapy alone in 20 and a combination of chemotherapy and radiotherapy in 32. 5 received no treatment and details are unknown in 3. 47 patients (58%) relapsed a median of 19 months (0.5–180) after initial therapy. Sites of relapse included brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Patients treated with ocular therapy alone did not have an increased risk of failing in the brain (p = 0.6). Progression free survival (PFS) and overall survival (OS) were 29.6 and 57 months respectively and were unaffected by the choice of therapy. CNS disease was the cause of death in 19/33 (58%). Conclusions: In this series, treatment type did not affect sites of relapse, PFS or OS in patients with PIOL. To minimize toxicity, the best initial therapy should be limited to intraocular chemotherapy or focal radiotherapy. Prospective clinical trials are needed to improve our understanding and treatment of this disease. No significant financial relationships to disclose.

Treatment outcomes for primary intraocular lymphoma: implications for external beam radiotherapy

Intravitreal chemotherapy for primary intraocular lymphoma (PIOL) increasingly is promoted as an alternative to radiotherapy, owing to putative high failure and complication rates of the latter modality. Our aim was to confirm whether these concerns about radiotherapy were borne out in patients treated at our institution over the last decade. Retrospective interventional case series. A total of 21 eyes of 12 patients with PIOL. Comprehensive chart review of ophthalmologic and systemic manifestations, treatments, and outcomes. Radiation complications and local tumour control. Cytology-confirmed lymphoma involved one eye in three patients and both eyes in nine patients. Initial treatment included external beam radiotherapy and chemotherapy (six patients), chemotherapy alone (four patients), radiotherapy alone (one patient), and no treatment (one patient). Ocular relapses occurred in no patients receiving radiotherapy and in two patients who did not receive radiotherapy. Complications of radiotherapy included dry eye (four patients), cataract (four patients), and mild radiation retinopathy (two patients). Radiotherapy for PIOL is highly effective with acceptable complications. In the absence of a clear advantage to intravitreal chemotherapy, which involves repetitive injections and associated risks, radiotherapy may still be the most appropriate first-line treatment in most cases.

Pharmacokinetics and efficacy of ifosfamide or trofosfamide in patients with intraocular lymphoma

Background: The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has not yet been defined. The study assesses ifosfamide (IFO) and trofosfamide (TRO) for treating IOL.Patients and methods: We prospectively evaluated the efficacy and aqueous penetration of intravenous IFO, oral TRO and their active 4-hydroxy (4-OH) metabolites in 10 patients with IOL. Doses varied from 1500 to 2000 mg/m2/day on days 1–3 for IFO and from 150 to 400 mg/day (continuous or intermittent administration) for TRO. Four patients had newly diagnosed disease, and six had relapsed after pretreatment.Results: All patients responded to first treatment with IFO or TRO, and both of two patients responded to re-treatment with IFO on ocular relapse. Progression-free survival from the first treatment with IFO or TRO was ≥6–18 months. In six of six patients, 4-OH metabolites were detected in the aqueous humor at a concentration of 0.32–1.56μm immediately after IFO infusion with an aqueous/serum ratio of 0.19–0.54. 4-OH metabolites could be detected in one of three patients at a concentration of 7.2μm 3–16 h after ingestion of TRO.Conclusions: IFO and TRO are active in IOL. IOL patients evidence aqueous penetration of 4-OH metabolites after intravenous administration of IFO.

Intraocular lymphoma 2000–2005: results of a retrospective multicentre trial

The prognosis of intraocular lymphoma (IOL) is poor, and the optimal treatment has yet to be defined. This study assesses the clinical characteristics and outcome of patients with IOL diagnosed and treated in the new millennium. Patient data in this retrospective multicentre study were compiled by standardised questionnaires sent to seven university ophthalmology departments. All cases diagnosed with primary and secondary IOL in the past 5 years not associated with HIV infection were included. Twenty-two patients, 11 men and women; median age 64 (range 38-83) years, median Karnofsky performance status 90% (range 50-100%), were included. Nineteen patients had primary IOL (PIOL): 13 a newly diagnosed disease and six an ocular relapse of primary central nervous system lymphoma (PCNSL). Three patients had secondary IOL. First-line treatment for IOL included systemic chemotherapy in 13 cases, ocular radiation in six and intraocular chemotherapy in three. Complete remission was achieved in 14/20 evaluable patients, partial remission in five and stable disease in one. All patients treated with ifosfamide (IFO) or trofosfamide (TRO) (n=8) responded. Median progression-free survival (PFS) and overall survival were 10 (range 1+ to 44.5+) and 22.5 (range 1+ to 49+) months, respectively. Patients with newly diagnosed PIOL and ocular relapse of PCNSL had a median PFS of 10 (range 1+ to 44.5+) and 6 (range 2 to 6+) months, respectively. Median PFS was 12 (range 3+ to 22.5+) months after systemic and 5.5 (range 1+ to 44.5+) months after local first-line therapy. The prognosis of PIOL is similar to that of PCNSL without ocular involvement. Systemic therapy possibly prolongs PFS as compared with local management of (P)IOL. The high response rate to monotherapy with IFO and TRO is promising.