HIV-infected individuals on long-term antiretroviral therapy are at higher risk for ocular disease.

Introduction of antiretroviral therapy (ART) has dramatically reduced the incidence of infectious ocular diseases in human immunodeficiency virus (HIV)-infected individuals. However, the effects of long-term ART and chronic HIV infection on the eye are ill-defined. This study determined the occurrence and severity of ocular diseases among 342 participants in a rural South African setting: HIV-naïve (n = 105), HIV-infected ART-naïve (n = 16), HIV-infected on ART for 36 months (long-term ART; n = 165). More HIV-infected participants presented with an external eye condition, in particular blepharitis, than HIV-naïve individuals (18% vs. 7%; age-adjusted odds ratio (aOR) = 2·8, P < 0·05). Anterior segment conditions (particularly keratoconjunctivitis sicca and pterygium) were also more common (50% vs. 27%; aOR = 2·4; P < 0·01). Compared with individuals on short-term ART, participants receiving long-term ART were more likely to have clinically detectable cataract (57% vs. 38%; aOR = 2·2, P = 0·01) and posterior segment diseases, especially HIV retinopathy (30% vs. 11%; aOR = 3·4, P < 0·05). Finally, long-term ART was significantly associated with presence of HIV retinopathy (P < 0·01). These data implicate that ocular disease is more common and of more diverse etiology among HIV-infected individuals, especially those on long-term ART and suggest that regular ophthalmological monitoring of HIV-infected individuals on ART is warranted.

Clinical and corneal microbial profile of infectious keratitis in a high HIV prevalence setting in rural South Africa.

The purpose of this investigation was to determine the clinical and corneal microbial profile of infectious keratitis in a high human immunodeficiency virus (HIV) prevalence setting in rural South Africa. Data in this cross-sectional study were collected from patients presenting with symptoms of infectious keratitis (n = 46) at the ophthalmology outpatient department of three hospitals in rural South Africa. Corneal swabs were tested for herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV) and adenovirus DNA by real-time polymerase chain reaction (PCR) and for bacteria and fungi by culture. Based on clinical history, disease characteristics and laboratory results, 29 (63 %) patients were diagnosed as viral keratitis, including 14 (48 %) viral keratitis cases complicated by bacterial superinfection, and 17 (37 %) as bacterial keratitis. VZV and HSV-1 DNA was detected in 11 (24 %) and 5 (11 %) corneal swabs, respectively. Among clinically defined viral keratitis cases, a negative viral swab was predominantly (93 %) observed in cases with subepithelial inflammation and was significantly associated with an increased duration of symptoms (p = 0.003). The majority of bacteria cultured were Gram-positive (24/35), including Staphylococcus epidermidis and S. aureus. Viral aetiology was significantly associated with a history of herpes zoster ophthalmicus (p < 0.001) and a trend was observed between viral aetiology and HIV infection (p = 0.06). Twenty-one (47 %) keratitis cases were complicated by anterior uveitis, of which 18 (86 %) were HIV-infected cases with viral keratitis. The data implicate a high prevalence of herpetic keratitis, in part complicated by bacterial superinfection and/or uveitis, in HIV-infected individuals presenting with infectious keratitis in rural South Africa.

Low level IGF-1 and common variable immune deficiency: an unusual combination.

A relation between growth hormone (GH) deficiency and immunoglobulin deficiency has been suggested previously in a few cases. We describe a patient with an insulin-like growth factor 1 (IGF-1) deficiency and common variable immune deficiency and briefly review earlier publications on the possible interaction between IGF-1 and the immune system. IGF-1 is the downstream mediator of GH. In this patient, GH and IGF-1 levels were both low. The GH response to a GH-releasing hormone test was normal whereas no subsequent IGF-1 response was seen. In our cohort of 14 patients with hypogammaglobulinaemia, two turned out to have slightly decreased IGF-1 serum levels and one patient with a thymoma had an increased IGF-1 level. Even though IGF-1 may be connected to B lymphocyte differentiation, in this patient we hypothesise there is a common impairment in the IGF-1 and IgG pathways.

[Behçet's disease and the possibilities of modern tumour necrosis factor inhibiting medication]. / De ziekte van Behçet en de mogelijkheden van moderne tumornecrosisfactor-remmende medicatie.

A 25-year-old woman was admitted after having had a fever for one month, headache, nausea, vomiting, dysarthria and right-sided hemiparesis. A 35-year-old man was admitted because of severe loss of vision and a history of focal retinochoroiditis. Both were suffering from Behçet's disease. Behçet's disease can present with systemic symptoms that might be related to aberrant T-cell functions. It is treated with a variety of immunoregulatory drugs. Recently, treatment with tumour necrosis factor (TNF) alpha-inhibiting molecular designed drugs such as infliximab or etanercept has improved the therapeutic prospective of Behçet patients. Both of the patients described above developed refractory disease and responded to treatment with these new drugs.

Anti-TNF-alpha therapy for sight threatening uveitis.

AIM: To describe the effect of additional treatment with anti-TNF-alpha therapy in a case series of 13 patients with serious sight threatening uveitis. METHODS: 13 patients with serious sight threatening uveitis were included, of whom six had Behçet's disease, five had idiopathic posterior uveitis, one had sarcoidosis, and one birdshot retinochoroiditis. Onset and course of ocular inflammation, inflammatory signs, and visual acuity were assessed. Patients were treated with 200 mg (approximately 3 mg/kg) infliximab infusion. Repeat infusions were given based on clinical response. RESULTS: Infliximab treatment resulted in an effective suppression of ocular inflammation in all patients. In patients with non-Behcet's disease uveitis visual acuity in six out of eight improved or was stable. In patients with Behcet's disease visual acuity in five out of six improved or was stable. CONCLUSION: Anti-TNF-alpha treatment may be of value in the treatment of uveitis, and in patients with Behçet's disease, leading to suppression of ocular inflammation, vasculitis, and improvement of vision in the majority. Based on these results a controlled masked study is warranted.

Somatostatin-related therapeutics in ophthalmology: a review.

Somatostatin and its derivatives have been predominantly studied and succesfully used in endocrinological diseases. This article reviews the rationale of the use of somatostatin and its derivatives in ophthalmology based on current understanding of its action in the eye and summarizes previously published controlled studies and case series. The article points out future possible applications. Larger randomised controlled studies are necessary to confirm its current and future use. New ways of application could facilitate its broader use in ophthalmology.

Presumed optic nerve sheath meningioma diagnosed after complicated retrobulbar anesthesia.

We present a patient who developed acute visual loss and light flashes at retrobulbar anesthesia for cataract extraction. Vision improved only slightly after cataract surgery. Although traumatic optic neuropathy was suspected, the patient was diagnosed one year later with an optic nerve sheath meningioma (ONSM). ONSM is a rare, slow growing, benign tumour with highly variable clinical features. Diagnosis is often delayed. This case report demonstrates the diagnostic difficulty of this tumour.

Experience with cyclosporine in endogenous uveitis posterior.

Treatment with cyclosporine (CsA) has considerably improved the visual prognosis of patients suffering from endogenous posterior uveitis (EPU). However, the therapeutic benefits of CsA are partially outweighed by its many side effects, most notably nephrotoxicity and hypertension. Low-dose CsA regimens have reduced toxicity but have not been able to completely eliminate this problem. New therapeutic approaches, such as anti-tumor necrosis factor alpha treatment or immunosuppression with drugs including tacrolimus, sirolimus, and interleukin-2 receptor antibodies, are currently under evaluation. Hopefully such strategies will further reduce the morbidity of EPU and minimize the adverse effects associated with conventional therapies.

Autologous peripheral retinal pigment epithelium translocation in patients with subfoveal neovascular membranes.

AIM: To evaluate the possibility of translocating autologous peripheral retinal pigment epithelial (RPE) cells and enhance their adhesion to improve functional outcome after choroidal neovascular membrane extraction in patients with subfoveal neovascular membranes. METHODS: A prospective, non-controlled surgical study in eight consecutive patients operated between February and July 2001 with final data monitoring in July 2002. All patients had mixed subfoveal membranes of 2-4 disc diameters. Functional tests included Snellen vision and central fixation testing. During vitrectomy, after the extraction of the neovascular complex, 8 x 10(4)-16 x 10(4) RPE cells were removed from the periphery and translocated under the macula following the submacular injection of 2 microg of poly-L-lysine to promote adhesion of the cells. RESULTS: With a follow up ranging from 3 months to 16 months, a pigmented area was seen in the extraction bed of the neovascular membrane in only one patient. Fixation was at the edge of the extraction bed in three patients. Vision remained the same in five patients and deteriorated in three (all with retinal detachment). Retinal detachment due to proliferative vitreoretinopathy occurred in three patients. CONCLUSIONS: The translocation of autologous peripheral RPE cells after membrane extraction was technically possible in a sterile manner, but was associated with a high proliferative vitreoretinopathy rate and in the present series had no measurable positive effect on functional outcome.

Somatostatin in diabetic retinopathy.

Diabetic retinopathy is a leading cause of legal blindness in the adult population (30-70 year olds). The anatomical changes that occur in the retina during the course of disease are well defined in the literature but the causes are not yet fully understood. Laser photocoagulation of the retina and vitrectomy are currently used to treat diabetic retinopathy but the procedures are invasive and provide only temporary protection. The use of long-acting analogues of the naturally occurring peptide, somatostatin, has been considered by some a promising therapeutic option for retinopathy over the last decade. Experimental evidence supports its use in diabetic retinopathy but further clinical evidence, from larger treatment groups of longer trial duration, is required. Improved analogues with increased selectivity and modified bi-specific analogues are currently emerging and may help to make the use of somatostatin analogues a more realistic option in the treatment of diabetic retinopathy.

Herpes simplex virus type 1 (HSV-1)--induced retinitis following herpes simplex encephalitis: indications for brain-to-eye transmission of HSV-1.

Herpes simplex encephalitis is a severe neurological disease with high mortality and morbidity rates. Reactivated herpes simplex virus type 1 (HSV-1) can cause relapses and might even spread to the retina, where it can induce a potentially blinding eye disease, known as acute retinal necrosis. In the present study, the HSV-1 strains in the brain and eye of 2 patients with acute retinal necrosis following an episode of herpes simplex encephalitis were genotyped. The HSV-1 strains in both the brain and eye were identical in each patient, but they differed interindividually. The data suggest brain-to-eye transmission of HSV-1 in these patients.

Herpes simplex virus type 1 (HSV-1)--induced retinitis following herpes simplex encephalitis: indications for brain-to-eye transmission of HSV-1.

Herpes simplex encephalitis is a severe neurological disease with high mortality and morbidity rates. Reactivated herpes simplex virus type 1 (HSV-1) can cause relapses and might even spread to the retina, where it can induce a potentially blinding eye disease, known as acute retinal necrosis. In the present study, the HSV-1 strains in the brain and eye of 2 patients with acute retinal necrosis following an episode of herpes simplex encephalitis were genotyped. The HSV-1 strains in both the brain and eye were identical in each patient, but they differed interindividually. The data suggest brain-to-eye transmission of HSV-1 in these patients.

Intraocular T cells of patients with herpes simplex virus (HSV)-induced acute retinal necrosis recognize HSV tegument proteins VP11/12 and VP13/14.

It has previously been shown that T cells specific for the triggering virus infiltrate the eye of patients with herpes simplex virus type 1 (HSV-1)-induced acute retinal necrosis (ARN). The T cells were mainly directed against 0.67-0.73 HSV-1 map region encoded antigens. The fine specificities of genetically different T cell clones (TCC), obtained from affected eyes of 3 patients with HSV-induced ARN and reactive toward this genomic region of HSV-1, were analyzed with recombinant HSV viruses and synthetic peptides. For 1 patient, the HSV-1 UL46 gene encoded tegument protein VP11/12 was identified as the target antigen. Two separate CD4(+) T cell epitopes were defined in VP11/12. TCC from the other 2 patients recognized the HSV-1 UL47 gene encoded tegument protein VP13/14. Two separate CD4(+) VP13/14 T cell epitopes were identified in these patients. Analysis of the data indicates that HSV-1 VP11/12 and VP13/14 are major target antigens for T cells obtained from vitreous fluid samples of the HSV-induced ARN patients studied.

Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct antiproliferative effect on human retinal endothelial cells. The purpose of our study is to investigate the expression of somatostatin receptor (sst) subtypes and particularly sst subtype 2A (sst2A) in normal human macula, and to study sst2A in different stages of age-related maculopathy (ARM), because of the potential anti-angiogenic effect of somatostatin analogues. METHODS: Sixteen eyes (10 enucleated eyes, 4 donor eyes, and 2 surgically removed choroidal neovascular [CNV] membranes) of 15 patients with eyes at different stages of ARM were used for immunohistochemistry. Formaldehyde-fixed paraffin-embedded slides were incubated with a polyclonal anti-human sst2A antibody. mRNA expression of five ssts and somatostatin was determined in the posterior pole of three normal human eyes by reverse transcriptase-polymerase chain reaction. RESULTS: The immunohistochemical expression of sstA in newly formed endothelial cells and fibroblast-like cells was strong in fibrovascular CNV membranes. mRNA of sst subtypes 1, 2A, and 3, as well as somatostatin, was present in the normal posterior pole; sst subtypes 4 and 5 were not detectable. CONCLUSIONS: Most early-formed CNV in ARM express sst2A. The presence of mRNA of sst subtype 2A was observed in normal human macula, and subtypes 1 and 3 and somatostatin are also present. sst2A receptors bind potential anti-angiogenic somatostatin analogues such as octreotide. Therefore, somatostatin analogues may be an effective therapy in early stages of CNV in ARM.

Retinal vasculitis occurring with common variable immunodeficiency syndrome.

PURPOSE: To report severe retinal vasculitis causing decreased vision in three patients with the common variable immunodeficiency syndrome. METHOD: Case report. Three patients with common variable immunodeficiency syndrome developed decreased vision secondary to retinal vasculitis. Fluorescein angiography was performed in all three patients. Peribulbar injections were given in one patient, and two patients were treated with oral steroids and cyclosporin. RESULTS: All three patients were young and had classic common variable immunodeficiency syndrome. Bilateral retinal vasculitis and diffuse retinal edema were present in all three patients, and two patients had retinal neovascularization in the absence of ischemia. No evidence of intraocular infection was present, and none was detected systematically. Visual acuity decreased in five of the six eyes and was responsive to treatment in only one patient (both eyes). CONCLUSION: Retinal vasculitis may be another autoimmune manifestation of common variable immunodeficiency syndrome.

T cells specific for the triggering virus infiltrate the eye in patients with herpes simplex virus-mediated acute retinal necrosis.

Acute retinal necrosis (ARN) is a rare, potentially blinding retinal disease resulting from ocular infections with herpes simplex virus (HSV) or varicella-zoster virus (VZV). To determine the antigen specificity and functional characteristics of ocular infiltrating T cells in ARN, T cells were isolated and expanded nonspecifically from intraocular fluid (IOF) samples from 2 patients with HSV-1- and 3 with VZV-mediated ARN. HSV-specific T cell reactivity could be detected only in the IOF-derived T cell lines (TCLs) of the 2 patients with HSV-mediated ARN. These TCLs consisted of both HSV type-common and type-specific CD4+ and CD8+ T cell clones (TCCs) with differential T cell receptor usage. Irrespective of their phenotype, the TCCs were cytolytic and secreted interferon-gamma, tumor necrosis factor-alpha, interleukin-4, and interleukin-5. In both patients, the antigen specificity of a substantial number of HSV-1-specific TCCs could be mapped to approximately 0.67-0.73 HSV-1 map units. The data presented suggest the contribution of T cells, specific for the triggering virus, to the pathogenesis of ARN.