Dermal and conjunctival melanocytic proliferations in diffuse uveal melanocytic proliferation.

AIM: The goal of this case report is to describe the dermatologic and conjunctival findings in a case of bilateral diffuse uveal melanocytic proliferation (BDUMP), a paraneoplastic syndrome usually associated with gynecologic cancers. There is little information about other dermatologic melanocytic findings in these patients. METHODS: Histologic and fluorescent in situ hybridization (FISH) analysis of three separate skin biopsies, one of which was separated by 21 months from the others, were performed in a 71-year-old patient with BDUMP to assess for histologic and chromosomal abnormality. Conjunctival histologic evaluation was also done. RESULTS: Dermal melanocytic proliferation was seen in each specimen. The cells were spindle type with mitotic activity. FISH analysis showed a normal copy of chromosomes. The conjunctival sample also showed normal FISH analysis. CONCLUSION: BDUMP is associated with multifocal dermal and conjunctival melanocytic proliferation.

Reticular pseudodrusen: a tale of two species?

INTRODUCTION: The anatomic localization of reticular pseudodrusen (RPD) has been an important area of research study. METHODS: A multimodal imaging analysis was conducted of two patients who were classified as having presumed RPD. RESULTS: Analysis of case 1 lends credence to original histopathologic evidence suggesting a choroidal origin of RPD, and analysis of case 2 supports RPD as originating above the RPE. CONCLUSION: This case series demonstrates that RPD may represent a compilation of diseases rather than one distinct clinical entity.

The effects of intraocular silicone oil placement prior to iodine 125 brachytherapy for uveal melanoma: a clinical case series.

PURPOSE: To investigate the role of silicone oil as an adjunct to iodine 125 ((125)I) brachytherapy in attenuating radiation dose and reducing radiation retinopathy. METHODS: A 16-mm COMS plaque loaded with (125)I seeds was simulated in vitro on an eye model containing silicone oil as a vitreous substitute using BrachyDose. The radiation dose ratio of silicone oil vs water to ocular structures was calculated at angles subtended from the centre of the eye. Silicone oil was then used in three choroidal melanoma patients who underwent 23-gauge vitrectomy, silicone oil placement, and (125)I brachytherapy. RESULTS: Silicone oil reduced the ocular radiation dose in vitro to 65%. Radiation dose ratios on the retina increased from 0.45 to 0.99 when moving from points diametrically opposed to the plaque's central axis. In 10-24 months' follow-up, no patients have developed radiation retinopathy. Each patient required silicone oil removal and experienced cataract progression, and one also developed a retinal detachment. CONCLUSIONS: This study confirms that silicone oil attenuates radiation dose in vitro, and may protect against radiation retinopathy clinically in patients, however it requires extensive surgical interventions. Further studies in only very selected populations using silicone oil as an adjunct to (125)I brachytherapy will best elucidate its role in shielding radiation retinopathy.

Histological findings of birdshot chorioretinopathy in an eye with ciliochoroidal melanoma.

PURPOSE: To describe the histological findings of birdshot chorioretinopathy. DESIGN/PARTICIPANT: This is a case study of a single patient who has both birdshot chorioretinopathy and ciliochoroidal melanoma. METHODS: A 55-year-old woman who was HLA-A29 positive and had birdshot chorioretinopathy had a large ciliochoroidal melanoma (T4b N0 M0) and underwent enucleation. OUTCOME MEASURES: Using histopathology, we hope to further define the pathological findings in an eye with both birdshot chorioretinopathy and coexistant ciliochoroidal melanomas. RESULTS: The eye showed a ciliochoroidal melanoma. In addition, elsewhere, there were multiple choroidal nodules of lymphocytes that showed the presence of CD3-positive cells, which also stained for CD4 or CD8. There were only a few CD20-positive B cells and rare CD68-positive histiocytes. No granulomas were present. DISCUSSION: To our knowledge, there are only two previous reports describing the histological findings in birdshot chorioretinopathy: one that was HLA-A29 negative showing choroidal granulomas and another that was HLA-A29 positive exhibiting histological findings similar to our case. Incidentally, the latter case had a history of cutaneous melanoma. CONCLUSION: Birdshot chorioretinopathy is a nongranulomatous nodular infiltration of the choroid.

Anterior segment changes following intravitreal bevacizumab injection for treatment of neovascular glaucoma.

BACKGROUND: The purpose of this study was to describe anterior segment changes in a prospective, interventional, noncomparative case series of patients with neovascular glaucoma secondary to proliferative diabetic retinopathy treated with intravitreal bevacizumab. METHODS: Five consecutive patients with neovascular glaucoma and a refractory, symptomatic elevation of intraocular pressure and pronounced anterior segment congestion received intravitreal bevacizumab 1.25 mg/0.05 mL. Follow-up examinations were performed at 4-16 weeks by the same specialists, with testing performed at hour 48, week 1, and months 1, 3, and 6 after intravitreal bevacizumab. RESULTS: We observed a significant difference (P = 0.021) between initial and mean neovascularization at three months in all the quadrants. At three months, median intraocular pressure was 19 ± 5.38 (range 12-26) mmHg. In three of the five cases, diode laser cyclophotocoagulation was required, and in one case a trabeculectomy was performed. One patient showed complete synechial angle closure 48 hours after treatment which required cyclodestructive procedures to normalize intraocular pressure. CONCLUSION: Intravitreal bevacizumab achieves complete regression of neovascularization in neovascular glaucoma secondary to proliferative diabetic retinopathy, and this regression is stable when associated with treatment of the underlying disease and should be investigated more thoroughly as an adjunct in the management of neovascular glaucoma.

Metastatic malignant melanoma.

Metastatic malignant melanoma is an incurable malignancy with extremely poor prognosis. Patients bearing this diagnosis face a median survival time of approximately 9 months with a probability of surviving 5 years after initial presentation at less than 5%. This is contrasted by the curative nature of surgical resection of early melanoma detected in the skin. To date, no systemic therapy has consistently and predictably impacted the overall survival of patients with metastatic melanoma. However, in recent years, a resurgence of innovative diagnostic and therapeutic developments have broadened our understanding of the natural history of melanoma and identified rational therapeutic targets/strategies that seem poised to significantly change the clinical outcomes in these patients. Herein we review the state-of-the-art in metastatic melanoma diagnostics and therapeutics with particular emphasis on multi-disciplinary clinical management.

Immediate intraocular pressure changes following intravitreal injections of triamcinolone, pegaptanib, and bevacizumab.

PURPOSE: To assess the intraocular pressure (IOP) changes, within the first 30 min after intravitreal injection of 0.1 ml (4 mg) triamcinolone, 0.09 ml (0.3 mg) pegaptanib, and 0.05 ml (1.25 mg) bevacizumab. METHODS: Records of patients who received intravitreal triamcinolone, pegaptanib, and bevacizumab and who had their IOP measured post-injection were reviewed. RESULTS: A total of 212 injections were performed (76 bevacizumab in 63 patients, 42 triamcinolone in 41 patients, 94 pegaptanib in 74 patients). At 10 min, over 87% of eyes receiving each drug had an IOP of less than 35 mmHg. Three of the 42 eyes receiving intravitreal triamcinolone were treated with IOP-lowering drops for pressures of 44, 46, and 60 mmHg. No patients treated with intravitreal bevacizumab or pegaptanib received IOP-lowering drops. The number of eyes in each injection group that had an IOP rise >10 mmHg within 30 min after injection was 27.6% of eyes receiving bevacizumab, 33.3% of eyes receiving triamcinolone, and 36.2% of eyes receiving pegaptanib. At 10 min, eyes with glaucoma were less likely to have an IOP<35 mmHg, but this difference became less marked with time. CONCLUSION: In our series, most patients receiving intravitreal injections did not require IOP-lowering drops after injection, and none required a paracentesis.

Changes in fundus autofluorescence of choroidal melanomas following treatment.

PURPOSE: We have previously shown that fundus autofluorescence (FAF) associated with pigmented choroidal lesions can be attributed to mainly lipofuscin (orange pigment) but also to hyperpigmentation, drusen, or fibrous metaplasia. The purpose of this study is to describe the effects of treatment on FAF in choroidal melanomas after plaque radiotherapy alone or in combination with transpupillary thermotherapy (TTT). METHODS: Retrospective chart review of eight consecutive patients with choroidal melanoma treated with plaque radiotherapy alone or in combination with TTT who underwent FAF photography before and after treatment. The correlation between FAF patterns and foci of orange pigment, hyperpigmentation, drusen, or fibrous metaplasia was evaluated. RESULTS: The median follow-up time was 4 (range 2-9) months. Foci of orange pigment and hyperpigmentation became larger and more numerous after treatment. Fibrous metaplasia was also increased. A complete correlation between increased FAF and orange pigment was found in all eight tumours (100%) before and after treatment. No correlation between hyperpigmentation and increased FAF was found before treatment but a partial correlation was found in all eyes after treatment. Before treatment, correlation between fibrous metaplasia was present in three eyes and increased FAF was partial in two eyes with no correlation in one case. After treatment, this correlation was partial in all presenting eyes (7). CONCLUSIONS: Following treatment, choroidal melanomas may show increased FAF, mainly due to an increase in the amount of lipofuscin (orange pigment) and hyperpigmentation.

Review of fundus autofluorescence in choroidal melanocytic lesions.

Fundus autofluorescence (FAF) imaging takes advantage of the fluorescent properties of some molecules, especially lipofuscin. FAF derives mainly from retinal pigment epithelium (RPE) and Bruch's membrane. Using confocal scanning laser ophthalmoscope (cSLO) we have previously shown that FAF associated with pigmented choroidal lesions can be attributed to mainly lipofuscin (orange pigment) within the RPE. Other causes of FAF include hyperpigmentation, drusen, or fibrous metaplasia probably because they also cause lipofuscin accumulation in the overlying RPE. There is a total or partial correlation between FAF and the foci of lipofuscin and hyperpigmentation in about 90% of the cases. The FAF patterns of choroidal melanocytic lesions were classified as patchy or diffuse. The patchy pattern was defined as the presence of distinct areas of increased FAF between areas of normal autofluorescence. The diffuse pattern was characterized by the presence of increased FAF with indistinct borders over a larger part (>50%) of the tumour in the absence of such intervening areas. Choroidal melanomas presented with either a diffuse or patchy pattern, whereas choroidal naevi demonstrated only the patchy pattern. Diffuse FAF pattern was more often associated with larger choroidal melanomas as well as with early venous and late hyperfluorescence on fluorescein angiography. Limitations of these observations depend on the field of depth of cSLO; thus, FAF from other planes could not be detected. Increased retinal thickness, intraretinal oedema, or presence of subretinal fluid may also affect the FAF signal.

Initial results of QuantiFERON-TB Gold testing in patients with uveitis.

PURPOSE: To describe the use of the second-generation QuantiFERON-TB Gold (QFT-G) test in a series of patients in an ophthalmic practice. METHODS: The charts of all patients who had QFT-G tests ordered by Mayo Clinic ophthalmologists in the past 3 years were reviewed. RESULTS: A total of 27 QFT-G tests were ordered. Thirteen (48%) tests were negative, six (22%) were indeterminate, two (7%) tests were re-ordered after a lab accident or an improper cancellation, four (15%) were positive and represented infection, and two (7%) were positive but negative when re-tested. Of the four truly positive cases, three were treated for tuberculosis (TB): one had tuberculous iritis, one had retinal vasculitis and haemorrhage, and one had asymptomatic TB but was on immunosuppressive therapy. The fourth patient had previously been treated for latent infection. CONCLUSIONS: In a series of selected patients with uveitis, the QFT-G test was able to detect TB infection in 15% of the patients, though it does not differentiate between active and latent TB infection. QFT-G should be considered in place of purified protein derivative testing in those with uveitis that have had prior BCG vaccination and in immunocompromised patients. Patients with a positive QFT-G, but who have little risk for TB infection and a negative systemic work-up, should be re-tested.

Chorioretinitis and vitreitis due to Tropheryma whipplei after transplantation: case report and review.

Whipple's disease is a very rare chronic multisystemic bacterial disease characterized by diarrhea, malabsorption, fever, and polyarthritis. Ocular manifestations occur very rarely. Previous reports have suggested that the use of immunosuppressive drugs appears to accelerate or exacerbate the clinical course of Whipple's disease; however, the illness has yet to be reported in the setting of transplantation. Herein, we describe what we believe is the first reported case of Whipple's disease after transplantation. The patient is a 51-year-old woman who developed progressive visual floaters and blurring of vision 30 years after living-related kidney transplantation for an autosomal-dominant polycystic kidney disease. Her allograft was functioning well on maintenance immunosuppressive therapy with azathioprine and prednisone when she developed visual abnormalities. Transient weight loss, gastrointestinal symptoms, and migratory polyarthralgia predated the onset of ocular disease by several years. The diagnosis of Whipple's bilateral vitreitis and chorioretinitis was confirmed by polymerase chain reaction analysis demonstrating Tropheryma whipplei nucleic acid in vitreous fluid and peripheral blood sample as well as by demonstration of the bacilli by cytopathology. Intraocular vancomycin, intravenous ceftriaxone, and prolonged course of oral trimethoprim-sulfamethoxazole therapy led to clinical improvement and recovery of visual acuity.

Immune cells in the human choroid.

AIM: To characterise the leucocytes in human macular choroid with and without drusen, and in eyes with advanced age-related macular degeneration (AMD) with fibrovascular scarring (FVS). METHODS: Ten eyes from nine donors (range 55-91 years of age) were obtained from an eye bank within 38 h post mortem. Fixed macular biopsies were sectioned, stained immunochemically and examined for the presence of leucocyte antigens CD45, CD4, CD8, CD14 and CD83. RESULTS: Four eyes without drusen, four eyes with drusen and two eyes with FVS contained 23.9 (SD 6.2)%, 27.5 (7.2)%, and 19.3 (11.3)% CD45-positive cells, respectively. The corresponding percentages for CD4-positive cells were 5.4 (4.3), 8.9 (3.0) and 7.5 (8.1); for CD8-positive cells, 3.8 (0.7), 6.8 (2.2) and 6.3 (2.1); and for CD14-positive cells, 3.7 (3.7), 3.6 (1.6) and 2.6 (3.6), respectively. The authors found CD83-positive cells solely in one of the two FVS eyes examined that had the more severe form of scarring. CONCLUSION: Human choroid contains similar amounts of CD4-positive cells and monocytes irrespective of the presence of drusen, but CD8-positive cells are more abundant in macular choroid with drusen. The presence of haematopoietic cells in the macular choroid provides further evidence for the possible participation of inflammatory cells in pathogenesis of AMD.

Histologic studies of the intraocular toxicity of imatinib mesylate in rabbits.

PURPOSE: To evaluate histologic signs of toxicity of the protein tyrosine kinase inhibitor, imatinib mesylate, in rabbit eyes. METHODS: Twenty Dutch-belted rabbits underwent intravitreal injections of 0.1 ml solutions of imatinib mesylate. Ten rabbits were killed and enucleated 1 week after injection of imatinib mesylate (1.65 mg (four eyes), 165 microg (four eyes), and 16.5 microg (two eyes)). Ten rabbits injected with imatinib mesylate (165 microg (five eyes) and 825 microg (five eyes)) were enucleated 1 month later. Eyes were fixed in 10% formalin and stained with haematoxylin and eosin for microscopic examination. RESULTS: All four eyes injected with 1.65 mg of imatinib mesylate and enucleated at 1 week demonstrated ocular toxicity. All four eyes injected with 165 microg and enucleated at 1 week showed no ocular toxicity. One of the two eyes injected with 16.5 microg and enucleated at 1 week revealed focal areas of subretinal fluid and retinal undulations, suggestive of retinal oedema. None of the 10 eyes injected with imatinib mesylate at either the 165 or 825 microg dose and enucleated at 1 month showed ocular toxicity. CONCLUSIONS: Imatinib mesylate at 1.65 mg caused extensive retinal toxicity in rabbit eyes. In contrast, lower doses did not appear to cause toxicity, but may be associated with retinal oedema.

Amino-acid levels in subretinal and vitreous fluid of patients with retinal detachment.

PURPOSE: To compare the concentration of amino acids in subretinal and vitreous fluid of patients with primary rhegmatogenous retinal detachment to that of control vitreous. METHODS: This prospective, observational study measured amino-acid levels in subretinal fluid of patients undergoing scleral buckle placement (n=20) and vitreous fluid in patients undergoing pars plana vitrectomy (n=5) for primary retinal detachment. Vitreous fluid from patients undergoing vitrectomy for macular hole (n=7) or epiretinal membrane (n=3) served as a control. Subretinal fluid and control vitreous were analysed using high-pressure liquid chromatography. Retinal detachment vitreous was analysed using capillary electrophoresis-laser-induced fluorescence. RESULTS: Mean levels of glutamate (27.0+/-1.7 microM), aspartate (4.1+/-4.0 microM), and glycine (44.1+/-31.0 microM) in subretinal fluid and glutamate (13.4+/-11.9 microM) in the vitreous were significantly elevated in retinal detachment compared to control vitreous. A significant, positive association was observed between levels of aspartate and glutamate in subretinal fluid (Spearman's correlation coefficient: 0.74, P<0.01). Mean arginine levels did not differ significantly between subretinal fluid and control vitreous. Levels of alanine, tyrosine, valine, isoleucine, leucine, and phenylalanine were significantly lower in subretinal fluid compared to control vitreous (all P<0.01). CONCLUSIONS: Glutamate levels in subretinal fluid and vitreous of patients with primary retinal detachment is significantly elevated in comparison to control vitreous. This finding lends further support to the hypothesis that elevated glutamate levels may result from ischaemia of the outer retina secondary to retinal detachment.