M. D. De Smet

Intraocular lymphoma : clinical and histopathologic diagnosis

BACKGROUND Intraocular lymphoma is associated with significant morbidity and mortality, but early diagnosis and treatment may improve prognosis. METHODS The diagnostic features of 12 cases of intraocular lymphoma diagnosed at the National Eye Institute between 1984 and 1992 were retrospectively reviewed. RESULTS A pathologic diagnosis of large B-cell lymphoma was made on vitrectomy specimens in ten patients, cerebral spinal fluid in one, and on an enucleation specimen in one. The mean time from onset of symptoms to diagnosis was 21.4 months (range, 1-66 months). All 12 patients were given a final diagnosis of non-Hodgkins lymphoma of the central nervous system (NHL-CNS), based on the epidemiology, pathology, and clinical course of their tumors. Although an initial vitrectomy was negative for malignant cells in three of ten patients, a repeat vitrectomy specimen subsequently showed intraocular lymphoma. Results of examination of the cerebrospinal fluid (CSF) showed malignant cells in 5 of 11 patients, although malignant cells were only identified after repeat examination of additional samples of CSF in three of these patients. Malignant cells often are difficult to identify, and an experienced cytopathologist was critical in making the correct diagnosis. In addition, corticosteroids are lympholytic to the lymphoma cells, and they appeared to decrease the viability of tumor cells obtained in samples of vitreous and CSF. CONCLUSION The prompt, appropriate handling of specimens and review by an experienced cytopathologist are critical to the diagnosis of intraocular lymphoma. Malignant cells often are present in the cerebral spinal fluid at the time that ocular lymphoma is diagnosed. Nevertheless, multiple vitrectomies and lumbar punctures may be necessary before the correct diagnosis is made.

Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma

AIM To develop and assess a protocol for the treatment of intraocular lymphoma by intravitreal injection of methotrexate and thiotepa. METHODS A patient with intraocular non-Hodgkin’s lymphoma which recurred after radiotherapy and repeated systemic chemotherapeutic regimens underwent repeated intravitreal injections of methotrexate and thiotepa. The patient was closely monitored by cytology, anterior chamber flare measurements, IL-10 and IL-6 levels. Methotrexate drug clearance studies were performed on vitreous samples taken before each injection. RESULTS Complete tumour clearance was achieved by the third week of therapy. IL-10 and IL-6 levels quickly dropped to barely detectable levels as the tumour was cleared from the eye. Flare measurements decreased from 500 to 15 photons/s over the same time. A plot of the methotrexate levels over time revealed a first order kinetic rate of elimination with an effective tumoricidal intravitreal dose persisting for 5 days after injection. CONCLUSION Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma appears effective in prolonging local remission of ocular disease even in the presence of an aggressively growing tumour. A single intravitreal injection of methotrexate can lead to a prolonged tumoricidal concentration lasting for a longer period than that achieved by systemic administration.

Influence of cataract on optical coherence tomography image quality and retinal thickness

Background: As optical coherence tomography (OCT) is widely used for diagnosis and monitoring of ocular pathology, especially in the elderly people, the influence of cataract on image quality and macular retinal thickness was studied. Methods: In 29 patients scheduled for cataract surgery, preoperative and postoperative OCT scans were obtained. Cataracts were categorised as nuclear, posterior or cortical. Parameters for image quality (signal-to-noise ratio (SNR)) and signal strength and macular thickness were compared. A three-level expert grading scale was used to evaluate the discriminative abilities of SNR and signal strength. Results: Nuclear cataracts (n = 12) provided better preoperative scans (higher SNR/signal strength) than posterior (n = 7) and cortical (n = 10) cataracts (p<0.004). Postoperatively SNR and signal strength increased significantly in all patients (p<0.001). The SNR was better at discriminating poor from acceptable and good scans than signal strength (area under the receiver operating curve: 0.879 and 0.810, respectively). Postoperative macular thickness overall showed a significant increase (p = 0.005), most evident in patients with posterior cataracts (p = 0.028). Conclusions: OCT imaging is influenced by cataract; image quality is reduced preoperatively and macular thickness measurements are slightly increased postoperatively. In individual patients, OCT scans remain reliable for gross clinical interpretation, even in the presence of cataract.

Uveitic macular oedema: correlation between optical coherence tomography patterns with visual acuity and fluorescein angiography

Aims: (1) To associate optical coherence tomography (OCT) patterns with particular fluorescein angiography (FA) findings in uveitis patients with macular oedema. (2) To investigate the correlation between tomographic features and visual acuity (VA). (3) To determine the impact of OCT patterns on visual improvement over time. Methods: 129 eyes of 90 patients followed for uveitis with macular oedema and adequate media clarity were consecutively included from February to November 2004. We examined the relationship between VA, the fluorescein angiograms grading and central thickness. Results: Mean retinal thickness at the central fovea was 357 (SD 128) µm. The mean VA was 0.5 (logMAR). There was agreement between OCT and FA in 112 eyes (86.8%). In eight eyes (6.2%), serous retinal detachment (SRD) was detected on OCT but not on FA. Nine eyes (7%) had perifoveal leakage on FA without macular thickening on OCT. There were three patterns of macular oedema on OCT: diffuse macular oedema (DMO), cystoid macular oedema (CMO) and SRD. CMO was detected in 61 eyes (50.8%), and in 18 of these eyes (15%), CMO was associated with SRD. DMO was detected in 45 eyes (37.5%), and in eight (6.7%) of these eyes, DMO was associated with SRD. SRD without retinal thickening was present in 14 eyes (11%). Epiretinal membrane was detected by OCT in 27 eyes (21%). Six eyes demonstrated vitreomacular traction (4.7%). There was a correlation between VA and central thickness on OCT (r = 0.407, p = 0.000001). Correlation between VA and central thickness is significant in the group with CMO (r = 0.401, p = 0.001) but not significant in the group with DMO. Furthermore, vision recovery was observed in patients with CMO but was limited in patients with DMO. SRD did not have a significant impact on visual recovery, but its presence reduced the correlation between vision and central thickness. Conclusion: OCT is effective in detection of macular oedema. It allows determination of the distribution of fluid and quantification of retinal thickness particularly in patients with CMO. In these patients, a potential for vision recovery was also identified. DMO was associated with a poor visual prognosis and a poor prognosis for vision recovery. SRD is associated with a high probability of vision recovery when observed alone or underlying CMO eyes. It should be substracted from the central thickness measurement when attempting to correlate central thickness with vision in patients with macular oedema in uveitis.

Evaluation of central serous retinopathy with en face optical coherence tomography

Background: The diagnosis of idiopathic central serous retinopathy (CSR) is usually based on biomicroscopy and fluorescein angiography (FA). The optical coherence tomography (OCT) ophthalmoscope produces en face OCT scans (OCT C-scans) and provides additional information not readily available by conventional imaging techniques. The authors describe the characteristic features observed in patients with a clinical diagnosis of CSR using the OCT ophthalmoscope. Methods: 38 eyes with a clinical diagnosis of CSR, seen at the Academic Medical Centre (Amsterdam, Netherlands) and the New York Eye and Ear Infirmary (New York, USA) between August 2002 and March 2004, were evaluated with standard digital FA and scanned with the OCT ophthalmoscope. Results: Nine of 38 eyes had no serous neurosensory detachment (inactive CSR) when scanned with the OCT ophthalmoscope. Characteristics for active CSR (n = 29) were large neurosensory detachment (23/29), subretinal hyper-reflective deposits (20/29), and pigment epithelial detachment (15/29). One third of the patients, either active or inactive, had multiple small pigment epithelial detachments located both within and outside the neurosensory detachment. Conclusion: The OCT ophthalmoscope provides complementary morphological information on patients with CSR. The presence of more diffuse retinal pigment epithelium (RPE) changes lends further support to the concept that CSR is a diffuse rather than localised RPE anomaly.

IRIS INVOLVEMENT IN PRIMARY INTRAOCULAR LYMPHOMA: REPORT OF TWO CASES AND REVIEW OF THE LITERATURE

Non-Hodgkins lymphoma involves ocular tissues either as a primary tumor or as secondary metastasis from systemic disease. Diagnosis is based on the identification of malignant cells in the eye by biopsy. Although primary intraocular lymphoma cells have been identified in the optic nerve, ciliary body, and iris of a small number of patients by histopathology, these sites of infiltration have rarely been observed on clinical examination. We studied clinical and histopathological findings of two patients with iris infiltration by primary intraocular lymphoma and reviewed the findings of 163 cases reported in the literature.

Treatment of autoimmune uveoretinitis in the rat with rapamycin, an inhibitor of lymphocyte growth factor signal transduction

Rapamycin (RAPA) is a macrolide antibiotic with unique immunosuppressive properties. RAPA inhibits T-cell function by interfering with IL-2 and IL-4 signal transduction. It does not prevent IL-2 production or IL-2R expression. The efficacy of RAPA in the treatment of autoimmune diseases was evaluated using the experimental autoimmune uveoretinitis (EAU) model. EAU was actively induced in Lewis rats by immunization with S-antigen in Hunters adjuvant. RAPA and control vehicle were administered by continuous intravenous infusion over a 14 day period by miniosmotic pump. RAPA treatment initiated on the day of immunization or 7 days later was found to efficiently inhibit EAU induction. The minimal effective dose was 0.1 mg/kg/d. EAU inhibition was correlated with reduced number of cells in the immunization site draining lymph nodes, as well as with a shift and lowering of the peak of the lymphocyte proliferative response curve. The anti-S-antigen antibody response was delayed by 3 days under RAPA treatment and the serum levels lowered in a dose dependent manner. An initial body weight loss was observed during the first week of drug administration, but there was a normal weight gain afterward.

Added value of OCT in evaluating the presence of leakage in patients with age-related macular degeneration treated with PDT

BackgroundEvaluating the presence of leakage on fluorescein angiography (FA) in patients with age-related macular degeneration (AMD) retreated with photodynamic therapy (PDT) can be difficult. New diagnostic tools such as optical coherence tomography (OCT) might help to optimize PDT management.MethodsThirty AMD patients scheduled for regular follow-up FA in conjunction with PDT treatment were also scanned with OCT. Follow-up data at 9 months were retrieved from the patients’ medical records. Inter-observer agreement [kappa (κ) coefficient] for the presence of leakage on FA, for OCT parameters for leakage, and agreement between FA and OCT evaluations were calculated. The indication for retreatment was evaluated using the leakage analysis based on FA alone, OCT alone, and both examinations combined, and compared to the actual follow-up of the patients at 9 months.ResultsAgreement between the two observers for the presence of leakage on FA was moderate (κ=0.51). OCT agreement between the two observers for the presence of leakage was good (κ=0.85). Agreement between FA and OCT for the presence of leakage was poor (κ=0.16). Follow-up data at 9 months on all patients were analyzed. Seven out of 30 patients were not retreated at the time of examination, and four of these patients (57%) remained stable without further treatment. Twenty-three patients did receive a PDT treatment at the time of examination; and eight of these patients did not show leakage on OCT, and five of these patients (62%) remained stable without additional treatment. In contrast, only three out of 15 patients (20%) with leakage on both FA and OCT remained stable during this 9 month follow-up period.ConclusionsInter-observer agreement for the presence of leakage was moderate for FA and good for OCT. There was considerable disagreement between leakage as judged by OCT and by FA. OCT could be of help in the decision regarding PDT retreatment. Assuming that 57% of the patients without leakage either on FA or OCT would remain stable without retreatment, the rate of probable ineffective retreatment could be reduced from 35% to 20%.

Effects of protease inhibitors on the course of CMV retinitis in relation to CD4+ lymphocyte responses in HIV+ patients

AIM To gain insight into the course of CMV retinitis (CMVR) in AIDS patients receiving protease inhibitors (PI), and to evaluate whether certain patterns of CD4 response are indicative of the clinical outcome and the risk of recurrence. METHODS 15 consecutive AIDS patients receiving maintenance therapy for CMVR were included in a prospective observational cohort study at the university hospital between July and October 1996. Patients were evaluated for signs of CMVR activity and intraocular inflammation. CMVR recurrence was defined as the primary clinical endpoint. Follow up was performed until July 1997. No patient was lost to follow up. Clinical outcome was related to CD4+ lymphocyte counts, which were monitored every 6 weeks. Highly active antiretroviral treatment regimen including PI was started at study entry. RESULTS All recurrences (n=7) were in patients who failed to have a sustained increase in CD4 counts, whereas CMVR remained inactive during a follow up of 42–52 weeks in those who were able permanently to restore their CD4 values to 100×106/l or more (n=5). The remaining three patients died after 12, 16, and 50 weeks, respectively, without recurrences. All relapses of CMVR were seen after 6–16 weeks, and at CD4 counts well below 100×106/l. CONCLUSIONS The beneficial effects of PI treatment correlate with the pattern of CD4 response. Sustained increases in CD4 counts achieved in the first 16 weeks of treatment are associated with a prolonged period of CMVR quiescence. Poor initial response is associated with a high risk of CMVR recurrence.

Aetiological study of the presumed ocular histoplasmosis syndrome in the Netherlands

AIM To investigate whether presumed ocular histoplasmosis syndrome in the Netherlands is caused by Histoplasma capsulatum and whether other risk factors might play a role in the pathogenesis of this syndrome. METHODS 23 patients were clinically diagnosed as having presumed ocular histoplasmosis syndrome based on the following criteria: peripapillary atrophy, punched out lesions, a macular disciform lesion or scar in one eye without vitritis. As controls, 66 sex and age matched healthy volunteers were used. Serum samples from both patients and controls were tested for the presence of antibodies againstH capsulatum, Toxoplasma gondii, Toxocara canis et cati,Ascaris sp, and for the presence of antigens of Cryptococcus neoformans. Serum samples were also tested for the presence of autoantibodies against retinal or choroidal proteins. To investigate other risk factors, patients and controls were asked to fill in a health and travel related questionnaire. Ten patients with ocular toxoplasmosis were used as a disease control group. RESULTS None of the patients with presumed ocular histoplasmosis syndrome or controls had circulating antibodies directed against H capsulatum. No risk factors could be identified and no indications for autoimmunity and no evidence for the role of the other infectious agents could be demonstrated. CONCLUSIONS In a Dutch group of patients fulfilling the criteria of a disease currently named presumed ocular histoplasmosis syndrome, no risk factors or relation with the fungus H capsulatum could be detected.