Structural changes of the choroid in sarcoid- and tuberculosis-related granulomatous uveitis.

AIM: The aim of this study is to characterise the choroidal features of patients diagnosed with sarcoid- and tuberculosis (TB)-associated granulomatous uveitis using spectral domain optical coherence tomography (OCT). METHODS: Twenty-seven patients (27 eyes) diagnosed with sarcoid- (13 eyes) and TB (14 eyes)-related uveitis were included in this retrospective, cross-sectional study. Over a six-month period, patients diagnosed with sarcoid and TB granulomatous uveitis were scanned using enhanced depth imaging OCT. Clinical and demographical characteristics were recorded, including the method of diagnosis, disease activity, site of inflammation (anterior or posterior), treatments, and visual acuity (VA). Manual segmentation of the choroidal layers was performed using custom image analysis software. RESULTS: The main outcome measure was OCT-derived thickness measurements of the choroid and choroidal sublayers (Haller's large vessel and Sattler's medium vessel layers) at the macula region. The ratio of Haller's large vessel to Sattler's medium vessel layer was significantly different at the total macula circle in eyes diagnosed with TB uveitis (1.47 (=140.71/95.72 µm)) compared with sarcoid uveitis (1.07 (=137.70/128.69 µm)) (P=0.001). A thinner choroid was observed in eyes with a VA ≥0.3 LogMAR (Snellen 6/12; 198.1 µm (interquartile range (IQR)=147.0-253.4 µm) compared with those with VA <0.3 LogMAR (292.4 µm (IQR=240.1-347.6 µm)) at the total macula circle (P=0.004). At the foveal central subfield, the median choroidal thickness was 336.8 µm (IQR=272.3-375.4 µm) in active compared with 239.3 µm (IQR=195.3-330.9 µm) in quiescent disease (P=0.04). CONCLUSION: A disproportionately enlarged Sattler's layer may indicate a diagnosis of sarcoid-related uveitis, and choroidal thickening may be a feature of active granulomatous uveitis.

Intravitreal triamcinolone injection for unresponsive cystoid macular oedema in probable Behçet's disease as an additional therapy.

BACKGROUND: We present the description of a successful outcome of intravitreal triamcinolone injection (IVTA) in a patient with cystoid macular oedema (CME) and severe retinal vasculitis suggestive of ocular Behçet's disease. HISTORY AND SIGNS: A healthy 32 year-old Caucasian man presented initially with right retinal vasculitis with preserved vision. Despite initial systemic treatment with high dose steroids, he developed CME with a reduction in vision. THERAPY AND OUTCOME: IVTA injection was carried out, and resulted in a good anatomic and functional response. The same picture developed in his left eye 2 months later and a similar response occurred following IVTA. Six months after the initial episode and despite treatment with cyclosporine and azathioprine, CME reoccurred in his RE inducing a decrease of his VA from 6/5 to 6/24. IVTA injection was repeated and a week later his VA increased to 6/6. At this stage patient was referred for initiation of therapy with infliximab. CONCLUSION: IVTA injection appears to be very helpful for the resolution of acute CME and for visual recovery, but we would like to emphasise that even though this approach seems to be helpful in an acute situation, the effect is short-lived and proper immunosuppression is needed for long-term control of the disease and its complications.

Treatment of ocular inflammatory conditions with loteprednol etabonate.

Ocular inflammatory diseases impose a significant medical and economic burden on society. Corticosteroids are potent anti-inflammatory agents that have been used successfully to treat ocular inflammation. Topical corticosteroids provide maximal drug delivery, and are used to reduce the signs and symptoms of intraocular and ocular surface inflammation. However, side effects associated with topical corticosteroids-including increased intraocular pressure, risk of cataract formation after long-term use, and decreased resistance to infection-are concerns. Loteprednol etabonate (LE) is an ester corticosteroid with a high therapeutic index that contains an ester, rather than a ketone, at carbon-20 of the prednisolone core structure. LE blocks the release and action of inflammatory mediators and is clinically effective in the treatment of steroid-responsive inflammatory conditions including giant papillary conjunctivitis, seasonal (intermittent) allergic conjunctivitis and uveitis. LE relieves ocular surface and lacrimal gland inflammation associated with dry eye and is used in combination with ciclosporin A as a treatment of dry eye. LE is also effective in the treatment of postoperative ocular inflammation. Because of its rapid de-esterification to inactive metabolites, LE appears to have an improved safety profile compared with ketone corticosteroids, and may be more suitable than ketone corticosteroids for the treatment for ocular inflammatory conditions in which long-term therapy is necessary. However, further comparative safety studies are needed.

Unilateral electronegative ERG of non-vascular aetiology.

BACKGROUND: Full field and pattern electroretinograms (ERG, PERG) are performed to assess generalised retinal function and macular function, respectively. An (electro) negative full field ERG usually describes an ISCEV standard maximal response in which the b-wave is smaller than a normal or minimally reduced a-wave and indicates dysfunction that is post-phototransduction. The most common cause of a unilateral negative ERG is central retinal artery occlusion (CRAO) or birdshot chorioretinopathy (BCR). This study examines the clinical and electrophysiological features of patients with unilateral negative ERG who do not have CRAO or BCR. METHODS: 12 patients were ascertained with a unilateral negative ERG in whom a vascular aetiology and BCR were excluded. Most presented with symptoms of central retinal dysfunction. In 11 of the 12 patients additional long duration photopic stimuli were used to test cone system ON and OFF responses. RESULTS: All 12 patients had unilateral electronegative bright flash full field ERGs indicating total or relative preservation of rod photoreceptor function, but dysfunction post-phototransduction. Seven of these patients had non-specific inflammatory changes in the eye with the negative ERG. Six patients, including five with inflammatory signs, had involvement of the cone ON response with complete preservation of cone OFF responses. A further three patients showed evidence of cone ON response abnormality with less severe OFF response involvement. CONCLUSION: The ERGs in this heterogeneous group of patients predominantly showed post-phototransduction involvement of the ON pathways. Sparing of the cone OFF response was often observed. The majority of patients had signs of previous inflammation and it is speculated that these highly unusual unilateral changes may be mediated via an autoimmune mechanism.

Vitreous surgery in the management of chronic endogenous posterior uveitis.

OBJECTIVES: There is evidence that pars plana vitrectomy (PPV) has a beneficial effect on the clinical course of chronic endogenous posterior uveitis (EPU) possibly by physically removing any resident inflammatory cells with the vitreous. We assessed the anatomical and therapeutic effects of PPV performed on patients with chronic EPU for any indication. PATIENTS AND METHODS: Retrospective review of 41 eyes of 38 consecutive patients with EPU who underwent a PPV for any reason, over a 5-year period. The mean age of the patients was 36.2 years, 46% of the eyes had intermediate uveitis, 32% panuveitis, and 22% posterior uveitis. The visual acuity, disease activity, and the requirement for medications to control it were recorded for 12 months pre- and postoperatively. RESULTS: Overall, 61% of the eyes gained more than 2 Snellen lines (P<0.001) and the incidence of cystoid macular oedema (CMO) significantly reduced from 44 to 20% (P<0.05). Postoperatively, there was a significant decrease in the recurrence rate of intermediate uveitis, posterior uveitis, and panuveitis (P<0.001). The use of systemic and local depot immunosuppressive agents did not change over the study period, although the use of topical agents increased (P<0.05). CONCLUSION: PPV appears to have a beneficial effect on the clinical course of EPU in selected cases. This may be mediated by the physical clearance of inflammatory debris, the anti-inflammatory effect of replacing vitreous by aqueous humour, by a reduction of CMO and/or the anatomical correction of sight-threatening retinal pathology.

Systemic disorders associated with episcleritis and scleritis.

Inflammation of the episclera and sclera still represents a diagnostic challenge. Many of these presentations are idiopathic and are managed empirically with the use of anti-inflammatory therapy, usually with a satisfactory response. However, some cases will have a more aggressive nature or will show resistance to conventional therapy, and those potentially are connected to an infectious or underlying disease. In such cases, there is an increased risk of visual loss and severe systemic complications requiring intensive investigations and aggressive therapy. The diseases more commonly associated with these conditions, especially with scleritis, are the connective tissue disorders and systemic vasculitis, but systemic infections and malignancies also must be excluded. Management depends on the specific diagnosis, and every year a new list of potential associations or atypical presentations is reported. For a successful outcome, it is important that these presentations are recognized.

The effect of pars plana vitrectomy in the management of Fuchs heterochromic cyclitis.

PURPOSE: Fuchs heterochromic cyclitis (FHC) is characterized by a unilateral chronic iridocyclitis of insidious onset and uncertain cause. Our aim was to evaluate the effect of vitreous surgery in patients with FHC and clinically significant visual symptoms caused by inflammatory vitreous debris. METHODS: This study was a review of 12 eyes of 12 consecutive patients with FHC who underwent pars plana vitrectomy for visually significant vitreous opacities. Cataract extraction with posterior chamber lens implantation had been performed on four eyes preoperatively. Four eyes had a concomitant lensectomy for cataracts, and one had a surgical posterior capsulotomy. Visual and anatomic data were recorded before surgery and for at least 6 months after surgery. RESULTS: Visual acuity improved in all patients from an average logMAR of 0.57 to 0.007 (P = 0.0004) and by more than 2 Snellen lines in 8 of 12 of the eyes (P < 0.05). Symptoms of floaters resolved in all 11 patients in whom they were a symptom. Vitreous haze was cleared completely from an average Nussenblatt grade of 1.7 to 0 after 1 week (P = 0.0001). CONCLUSIONS: Pars plana vitrectomy is a safe and effective treatment for the visual symptoms associated with FHC and can be combined safely with a lensectomy if required.

Cystoid macular oedema in uveitis: an unsolved problem.

Most papers on the subject of CMO associated with uveitis are retrospective, combine patients with different disease aetiologies, at different stages of evolution, and often describe patients who were previous treatment failures with other therapies besides the one under consideration. There are almost no prospective randomised double-masked controlled studies. This is perhaps in part due to the relative sparsity of uveitis patients seen by many uveitis centres. At the moment, treatment is largely empirical, based in large part on the studies, and others, quoted above. The need to regularly repeat courses of therapy, loss of efficacy of certain form of therapy after repeated use, and cumulative side-effects, all need to be taken into consideration when interpreting results and deciding upon the best approach to be adopted. The risks to the patient's well-being increase with the addition of systemic medication, and long-term steroid use can cause hypertension, induce or exacerbate diabetes, cause premature osteoporosis, cushingoid features, peptic ulceration and aseptic necrosis of the femoral head. Immunosuppressive drugs can be nephrotoxic, hepatotoxic, cause hypertension, gastric disturbances and excessive hair growth. The assessment of macular changes, both structurally and functionally, is the key aspect in understanding visual loss in CMO and also in predicting potential visualrecovery. The combined use of the various tools mentioned here, such as SLO, OCT and electrodiagnostic tests, may give us some of the necessary answers in this process. However, all these tests will need to be validated. A prospective analysis of CMO in cases of uveitis, especially if coupled with therapeutic intervention, will give us the opportunity to achieve this objective.

Incidence of symptomatic toxoplasma eye disease: aetiology and public health implications.

Ocular disease is the commonest disabling consequence of toxoplasma infection. Incidence and lifetime risk of ocular symptoms were determined by ascertaining affected patients in a population-based, active reporting study involving ophthalmologists serving a population of 7.4 million. Eighty-seven symptomatic episodes were attributed to toxoplasma infection. Bilateral visual acuity of 6/12 or less was found in seven episodes (8%) and was likely to have been transient in most cases. Black people born in West Africa had a 100-fold higher incidence of symptoms than white people born in Britain. Only two patients reported symptoms before 10 years of age. The estimated lifetime risk of symptoms in British born individuals (52% of all episodes) was 18/100000 (95% confidence interval: 10.8-25.2). The low risk and mild symptoms in an unscreened British population indicate limited potential benefits of prenatal or postnatal screening. The late age at presentation suggests a mixed aetiology of postnatally acquired and congenital infection for which primary prevention may be appropriate, particularly among West Africans.

Retinochoroiditis is induced by oral administration of Toxoplasma gondii cysts in the hamster model.

Administration of Toxoplasma cysts by intraperitoneal innoculation in the Syrian Golden Hamster provides a reproducible animal model of acquired Toxoplasmic retinochoroiditis and cysts are observed in the brain. However, toxoplasmosis is frequently acquired by oral ingestion of contaminated foodstuffs and it is recognised that the route by which disease is acquired may influence its pathogenesis and clinical expression. This study aimed to determine whether retinochorioiditis and cysts in the brain develop after oral ingestion in the Syrian Golden Hamster model as this is the route of induction akin to that in man and may therefore be more relevant in the study of disease pathogenesis. All animals developed disease by 4 weeks. Ocular and cerebral inflammation was confirmed by histology at 16 weeks and this was milder than in the original model.

Effects of drug therapy on Toxoplasma cysts in an animal model of acute and chronic disease.

PURPOSE: To evaluate the effects of drug therapy on the clinical course of acute acquired Toxoplasma retinochoroiditis and on the number of Toxoplasma cysts present in the brain and ocular tissues in the hamster animal model. METHODS: The Syrian golden hamster animal model of Toxoplasma retinochoroiditis was used. In acute disease, systemically administered atovaquone was compared with conventional therapies (pyrimethamine combined with sulfadiazine; clindamycin; and spiramycin). The clinical course of the ocular disease was determined with retinal examination and photography of the fundus. The number of Toxoplasma cysts remaining after treatment was evaluated in aliquots of brain homogenate and in retinal tissue. The effect of atovaquone on cerebral Toxoplasma cyst count was also studied in chronic disease. RESULTS: None of the drugs administered altered the course of the acute disease, judged by clinical examination. Atovaquone alone significantly reduced the number of cerebral Toxoplasma cysts after acute disease. Atovaquone also significantly reduced the cerebral Toxoplasma cyst count in chronic disease. CONCLUSIONS: Tissue cysts are believed to be responsible for reactivation of Toxoplasma retinochoroiditis. Atovaquone has the potential to reduce the risk of recurrent disease.