Demyelinating plaque-associated uveitis.

PURPOSE: To report the clinical and fluorescein angiographic (FA) features of demyelinating plaque-associated uveitis (DPU), a subset of uveitis in which patients have demyelinating plaques on the brain/cervical magnetic resonance image (MRI) but do not meet the criteria for multiple sclerosis (MS). METHODS: In this retrospective observational study, Persian Patients were diagnosed with DPU and included if (1) they never satisfied the MS criteria, (2) all other possible etiologies were excluded, and (3) they were followed for at least 2 years. RESULTS: After a median follow-up of 3 years (interquartile range, 2.0-5.3), 8 out of 40 (20%) patients diagnosed with DPU were excluded as they subsequently met the MS criteria. Of remaining 32 patients studied, the mean age was 36.3±9.9 (range 20-56 years), and 30 (93.8%) were female. Twenty-four (75.0%) showed bilateral involvement and 27 (84.4%) had insidious-chronic course. Uveitis was classified as intermediate (with or without anterior uveitis) in 29 (90.6%) and isolated anterior in 3 (9.4%) patients. Nine (28.1%) patients had at least one systemic neurological complaint. Ocular findings were: granulomatous keratic precipitates in 43/44 (97.7%) eyes; snowballs in 25/52 (48.1%) eyes; snowbanks in 4/52 (7.7%) eyes; cystoid macular edema in 20/56 (35.7%) eyes; and optic neuritis in 5/56 (8.9%) eyes. Visual acuity was ≥ 20/40 in 39 eyes (69.6%) at presentation which improved to 46 eyes (81.2%) at 2-year follow up. The two most frequent findings in FA were optic disc leakage/staining in 44/52 (81.5%) eyes, and peripheral retinal perivascular leakage in 39/52 (76.9%) eyes, which in 14/52 (26.9%) eyes extended beyond the equator. CONCLUSION: DPU usually presents as a bilateral chronic granulomatous intermediate and, less often, isolated anterior uveitis, especially in females. Most are neurologically asymptomatic. Visual outcome is generally favorable. In FA, peripheral retinal perivascular leakage is common. DPU patients have an increased tendency to develop MS and should be prohibited from anti-TNF treatment.

Assessment of measurement methods of posterior inflammation in stromal choroiditis: the value of quantitative outcome measures versus the presently qualitatively based paradigm.

PURPOSE: To assess posterior inflammation using a fluorescein (FA)/indocyanine-green angiography (ICGA) scoring system, and compare them to the presently recommended outcome measure, the standardization of uveitis nomenclature vitreous haze score (SUN-VH) in stromal choroiditis. METHODS: This was a retrospective study on patients with a diagnosis of ocular sarcoidosis(OS), ocular tuberculosis(OT), Birdshot retinochoroiditis(BRC) and Vogt-Koyanagi-Harada disease(VKH) seen in the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland. Angiography signs were quantified according to an established FA/ICGA scoring system. Vitritis was assessed using SUN-VH. Results were compared. RESULTS: 65 newly diagnosed patients (128 eyes) with stromal choroiditis were included. Angiographic scoring showed variable degrees of choroidal versus retinal involvement (87% for OS, 72% for OT, 62.5% for BRC and 100% for VKH). On the other hand, a mere 22 of 128 eyes (17%) showed a SUN-VH score ≥ 2 necessary for inclusion in clinical trials. Moreover, FA/ICGA values followed a normal distribution curve and presented inter-examiner variations greater than 1-SD in only 8.4% of cases. SUN-VH values' distribution was non-normal and showed inter-examiner discrepancies greater than 1-SD in 51.7% of cases. CONCLUSION: This study highlights the precise measurement of global posterior inflammation achieved by a dual FA/ICGA scoring system in stromal choroiditis. In contrast, SUN-VH scale appears imprecise and inadequate, as only a minute percentage of the studied eyes could have been included in a clinical trial based on this criterion. To evaluate posterior intraocular inflammation meaningfully in stromal choroiditis, the use of dual FA/ICGA is strongly advised and should replace the presently recommended SUN-VH system.

Torpedo Maculopathy Associated with Choroidal Neovascularization.

Background Torpedo maculopathy is a very rare, congenital, usually unilateral hypopigmented lesion in the temporal macula. Material and Methods This retrospective case series describes three patients with torpedo maculopathy. Results The first two cases demonstrate typical clinical and imaging findings of torpedo maculopathy in asymptomatic patients. The third case relates to a symptomatic young patient with a torpedo lesion, a smaller satellite lesion, and evidence of choroidal neovascularization confirmed by fluorescence angiography. In the area of the clinically visible torpedo lesion, spectral domain optical coherence tomography showed atrophy of the outer retina with increased choroidal signalling and a hyperreflective lesion above the retinal pigment epithelium suggestive of choroidal neovascularization. Fundus autofluorescence imaging revealed a hyperautofluorescent rim along the margin of the hypoautofluorescent torpedo lesion. Conclusion In the literature, torpedo lesions are usually regarded as benign lesions with no tendency for progression. The third case demonstrates that torpedo lesions may be associated with choroidal neovascularization, which has been successfully treated with anti-VEGF therapy.

SLO Fundus Imaging Is the Most Sensitive Modality of Multimodal Imaging for Macular Microembolisms with Subtle Signs.

Background. Microemboli of fat or other material into the terminal macular retinal circulation can be difficult to diagnose. We report 2 cases that showed subtle signs where SLO fundus imaging was most sensitive to precisely outline the limits of the inner retina infarction. Patients and Methods. Multimodal imaging analysis was performed including fundus photography, fluorescein angiography, indocyanine green angiography, Optical Coherence Tomography and SLO fundus imaging of 2 cases with suspected infarction of the inner retina. Cases. A 30-year-old man reported a grey central spot OD a few days after being squeezed between two cars with a sacrum fracture. Vision was 0.2 OD, and 1.0 OS. Examination was unremarkable and fluorescein angiography was normal. Octopus visual field showed a tiny central scotoma OD. Microperimetry showed decreased central sensitivity OD > OS. The only sign was a dark area on the SLO fundus picture indicating a subtle infarction of the inner retina (OD > OS) with nothing visible on the OCT. Resolution of lesions on the SLO picture ODS occurred in parallel with improvement of microperimetry and visual acuity. A 32-year-old woman suspected to take IV drugs had a sudden drop of vision to 0.4 OD and count fingers at 6 feet OS. Signs included macular hemorrhages and non perfusion on FA. The striking sign was a large dark area on the SLO picture precisely delineating the more extensive infarcted area of internal retina corresponding to OCT hyperreflectivity, visible in this case. Conclusions. Macular ischemia due to microemboli can show obvious fundus signs as hemorrhages, cotton wool spots and non perfusion or can present in a subclinical fashion. The SLO picture has a higher image contrast and higher resolution compared to conventional fundus photography and so can precisely delineate ischemic changes of the inner retina causing the unexplained visual loss.

Discrepancy between Visual Acuity and Microperimetry in AMD Patients: Visual Acuity Appears as an Inadequate Parameter to Test Macular Function.

BACKGROUND: Best corrected visual acuity (BCVA) of 0.8 or above in AMD patients can sometimes correspond to poor macular function inducing a serious visual handicap. Microperimetry can be used to objectivize this difference. PATIENTS AND METHODS: A retrospective study was undertaken on 233 files of AMD patients of whom 82 had had a microperimetry. BCVA was compared with microperimetry performance. All examinations were performed in an identical setting by the same team of 3 persons. RESULTS: Among the 82 patients included, 32 (39.0%) had a BCVA equal to or above 0.8 even though their microperimetry performance was lower than 200/560 db. 10 of them (12.2% of total) had an even poorer microperimetry below 120/560 db indicating poor macular function. CONCLUSIONS: More than a third of the AMD patients had a bad or very bad microperimetry performance in parallel with a good visual acuity. Microperimetry is a valuable tool to assess and follow real macular function in AMD patients when visual acuity alone can be misleading.

Psoriasis beyond the skin surface: a pilot study on the ocular involvement.

The ocular involvement in psoriasis is not a completely well-known problem. The ophthalmologic involvement occurs in about 10 % of patients, particularly in case of arthropathic or pustular psoriasis. Ocular lesions are more common in males, and they often occur during psoriasis exacerbations. Our study aimed to assess the prevalence and type of ocular involvement in psoriasis, by a comparison between psoriasis and healthy subjects, and if/how a 12-week long systemic immunosuppressive therapy is able to modify them. This study involved thirty-two psoriatic patients and thirty-two healthy subjects. Dermatological evaluation was done using Psoriasis Area and Severity Index, Physician Global Assessment, and Dermatology Life Quality Index (PASI, PGA, and DLQI score). Ophthalmological evaluation included ocular surface involvement (Schirmer, Jones, break-up time--BUT, DR-1 camera), retinal pathologies, and ocular surface disease index. Laboratory investigations including the C-reactive protein (CRP) of all the patients were performed. At baseline, the values of Schirmer, Jones, and BUT tests in the patient group were significantly lower compared to controls; moreover, conjunctival hyperemia was more frequent in psoriatic patients than in healthy subjects. Ocular involvement was more prominent in the subset of psoriatic patients with sebo-psoriasis than in general psoriatic population. A statistically significant correlation was found in sebo-psoriasis between PASI and Schirmer, between PASI and Jones, and between PASI and BUT. On the other hand, the results obtained from DR1 camera showed statistically significant difference between psoriatic and sebo-psoriatic patients at the end of the follow-up. After 12 weeks of treatment, the mean values of PASI, PGA, DLQI, CRP, and BUT showed significant changes in psoriatic patients. Our findings suggest a high rate of ocular involvement in psoriatic patients, emphasizing the need of performing periodic ophthalmological examinations in order to avoid underestimating eye diseases and to allow early diagnosis and treatment of patients.

Indocyanine green angiography (ICGA) is essential for the early diagnosis of birdshot chorioretinopathy.

BACKGROUND: Birdshot chorioretinitis (BC) is a rare disease involving the retina and the choroid independently. The hallmark for BC is the presence of depigmented oval lesion of the choroid, the so called "birdshot lesions", however in the early phase of disease these lesions are often not visible. METHODS: A retrospective analysis of BC patients that were investigated in Centre for Ophthalmic Specialised Care, Lausanne, Switzerland between 1995 and 2010 was performed. Patients seen in the initial phase of BC disease devoid of a specific diagnosis when referred were included. Clinical investigations along with fluorescein angiography (FA), indocyanine green angiography (ICGA) and visual field testing (VF) were analysed. RESULTS: Three out of 7 patients (43 %) seen in the initial phase of the disease devoid of a diagnosis at presentation were analysed. These patients presented with no "birdshot" lesions whatsoever. All three patients were HLA-A29 positive, presented with vitreitis and retinal vasculitis on FA. On ICGA, all 3 patients presented bilateral evenly distributed choroidal hypofluorescent dark dots (HDD) representing choroidal granulomas. CONCLUSIONS: ICGA, by providing occult information on the choroid, is an essential tool for early diagnosis of BC. Because ICGA is still not universally practiced in uveitis centres early disease is often missed, its diagnosis delayed and proper treatment started late.

Classification of choroiditis based on inflammatory lesion process rather than fundus appearance: enhanced comprehension through the ICGA concepts of the iceberg and jellyfish effects.

Choroidal inflammatory diseases have been classically grouped under the term of white dot syndromes (WDS), a term only based on the appearance (white-yellow dots) of inflammatory fundus lesions. This purely descriptive and vague terminology, regrouping a pot-pourri of posterior inflammatory conditions, probably came into use because the precise exploration of the choroid was not possible, and also because many of the diseases were rare and not well understood. Since the availability of indocyanine green angiography (ICGA) that allows one to explore the choroidal compartment, it became possible to understand the lesion mechanism of choroiditides and to classify this group of diseases according to their pathophysiological behaviour. It was our aim to show here that the term WDS is applied to and encompasses inflammatory conditions that are characterized by completely different lesion mechanisms and should therefore be classified separately from each other. ICGA made it possible to differentiate two types of choroiditides, including on the one hand inflammatory diseases of the choroidal stroma and on the other hand inflammatory diseases of the choriocapillaris. Unfortunately, twenty years after its advent, ICGA is still not used routinely in uveitis centres and the traditional inappropriate but overall useless term of WDS is still used, maintaining the confusion about these diseases. The aim of this work was (i) to illustrate that meaningful exploration of choroidal inflammation, mostly occult and inaccessible to usual investigations, has to be performed using ICGA, (ii) to insist on the crucial importance of ICGA in the management of choroiditis and (iii) to enhance the comprehension of the ICGA-based classification of choroiditis, by using the demonstrative and striking analogue concepts of iceberg and jellyfish effects.

Evolution of choroidal thickness over time and effect of early and sustained therapy in birdshot retinochoroiditis.

PurposeTo follow choroidal thickness (ChT) over time in birdshot retinochoroiditis (BRC) using enhanced depth imaging optical coherence tomography (EDI-OCT) and study the effect of early and sustained treatment on ChT.Patients and methodsEighteen patients were included and EDI-OCT measurements of ChT were analyzed retrospectively in five groups of patients with follow-up times ranging from 1 year to ≥15 years. The OCT images were evaluated and ChT was calculated under the foveola and 1500 µm temporal, nasal, superior, and inferior to the foveola. To assess the effect of treatment, 13 patients with a disease duration ≥10 years were divided into two groups depending on their treatment status: early and sustained therapy vs insufficient, late, or no treatment. ChT was compared in these two groups along with the number of typical fundus BRC lesions.ResultsThe ChT decreased (r=-0.41, P=0.0018) over the disease duration, which ranged from <1 year to ≥15 years. In patients with a disease duration ≥10 years, a significant difference in ChT was noted between adequately and undertreated patients (288.3±76.9 µm vs 161.4±39.2 µm; P=0.004). At the last follow-up, in the group with insufficient therapy 10 of 11 eyes presented typical fundus BRC lesions vs 2 of 13 eyes in the treated group (P≤0.0006, F-test).ConclusionsChoroidal thickness decreases significantly over time in BRC. If undertreated, patients show thinner choroids compared with adequately treated individuals and present significantly more BRC lesions.

Treatment of corneal allograft rejection with the cytotoxin IL-2-PE40.

IL-2-PE40 is a recombinant chimeric protein composed of IL-2, fused to a modified pseudomonas exotoxin. This molecule is extremely toxic to activated T cells expressing high-affinity IL-2R. We used this new molecule for selective immunosuppression to treat corneal allograft rejection in the rat, using Fisher and Lewis rats, a strain combination differing only in medial and minor histocompatibility antigens. The effect of IL-2-PE40 on the immunologic response was studied using both a heterotopic corneal graft model and orthotopic grafts. At the dose of 0.31 micrograms/g given intraperitoneally every 12 hr, IL-2-PE40 produced a significant reduction of both total lymph node cells and cytotoxic-T-cell (CTL) activity in draining lymph nodes (DLN) of heterotopically grafted animals. IL-2-PE40 treatment also significantly reduced the clinical rejection score and cumulative rejection rate (CRR) in orthotopic grafts and appears to be a very effective immunosuppressive agent.

Ocular inflammation stimulated by intravitreal interleukin-8 and interleukin-1.

Interleukin-8 (IL-8), a cytokine with neutrophil chemotactic and activating properties, is known to be stimulated by IL-1. Fischer rats are more resistant to inflammation than Lewis rats probably due to a higher corticosteroid stress response. To determine the role of IL-8 in ocular inflammation, the effect of intravitreal injection of IL-8 was compared with that of IL-1 in both Lewis and Fischer rats. The IL-8, IL-1 alpha, or sterile balanced salt solution (control) was injected into one eye of each animal. Both IL-8 and IL-1 alpha caused inflammation in the eye of both strains, as detected by leukocyte counts of the anterior chamber and histopathologic examination. The eyes of animals injected with a cytokine had significantly higher numbers of leukocytes compared with eyes of control animals. Histopathologic examination confirmed these findings. The IL-1 alpha induced inflammation more consistently and more severely than the most effective dose of IL-8. This finding agreed with the concept of IL-1 initiating a cascade of inflammatory mediators including IL-8, which acts more specifically on a smaller population of leukocytes. A contralateral response was observed in the uninjected eye of experimental and control animals. The contralateral response in animals receiving the cytokines was significantly greater than that in controls. Lewis rats show a higher inflammatory response to the injections than do the Fischer rats. These data suggest that IL-8 may be active as one component in neutrophil-mediated ocular inflammation.

Effects of the immunosuppressant FK506 on a penetrating keratoplasty rejection model in the rat.

PURPOSE: The immunosuppressive effects of FK506 on allogeneic corneal transplantation were tested in a rat model. METHODS: Inbred-strain Lewis rats were used as recipients, and Fisher rats were used as donors. Intraperitoneal injection of FK506 (0.3, 1.0, and 3.0 mg/kg per day) was administered for 2 weeks, and the grafts were inspected by clinical evaluation. Mixed lymphocyte culture assay, using lymphocytes from recipients of penetrating keratoplasty as responder cells and irradiated splenocytes from naive Fisher or Brown Norway as stimulator cells, was used to identify allogeneic stimulation. The rejection process was studied by histology and immunohistochemistry. RESULTS: The rat strain combination developed 100% graft rejection in about 2 weeks after the penetrating keratoplasty. FK506 prolonged the graft survival in a dose-dependent manner, as observed by clinical evaluation. In mixed lymphocyte culture assay, Lewis rats that had been primed to allogeneic stimulation at the time of cornea transplantation presented significant proliferation to Fisher stimulator splenocytes. FK506 suppressed this primed lymphocyte proliferation. Immunohistochemical and histologic studies confirmed the clinical evaluations. Untreated rat corneas, at the second postoperative week, presented a large number of helper/inducer T cells, macrophages, IL-2 receptor-expressing cells, and Ia-antigen-expressing cells. In the same period, FK506-treated rats appeared normal and had no cellular infiltration. Corneas rejected after FK506 cessation had less intense cell infiltration than the control corneas. CONCLUSIONS: These data indicate that FK506 prolonged the corneal graft survival and can be a potentially useful drug in the immunotherapeutic arsenal to suppress corneal graft rejection.

Inflammation patterns after laser trabeculoplasty measured with the laser flare meter.

Anterior chamber inflammation was measured in 71 eyes after argon laser trabeculoplasty with the laser flare-cell meter (Kowa FC-1000). Visual acuity, tonometry, and laser flare measurement were performed before and 3, 6, and 18 hours and 2, 4, 7, 14, 30, and 90 days after argon laser trabeculoplasty. Anterior chamber inflammation peaked 2 days after argon laser trabeculoplasty. Forty-nine percent of the eyes showed significant inflammation, with a flare increase of more than 10 photon counts per millisecond over prelaser values. Inflammation was significantly more frequent in pseudoexfoliative glaucoma (69%) and pigmentary glaucoma (100%) than in primary open angle glaucoma (23%). Post-argon laser trabeculoplasty relative pressure decrease was significantly more important in the group of patients with inflammation than in the group without inflammation in the early and late follow-up periods. Topical nonsteroidal anti-inflammatory treatment (diclofenac sodium) was needed in 17 patients, who readily responded to treatment within 72 hours.

Anti-inflammatory effect of diclofenac drops after argon laser trabeculoplasty.

Using a laser flare-cell meter, the anti-inflammatory effect of diclofenac sodium drops was evaluated after argon laser trabeculoplasty in a double-masked placebo-controlled study. Fifty-three eyes with pseudoexfoliative (43 eyes) or pigmentary glaucoma (10 eyes) were randomly assigned to treatment (n = 27) or placebo (n = 26) groups. Diclofenac (0.1%) or placebo drops were administered once before and after trabeculoplasty and then four times daily for a total of 4 days. Visual acuity, intraocular pressure, and anterior chamber flare, measured with the laser flare-cell meter, were evaluated before trabeculoplasty, 3 and 6 hours after trabeculoplasty, and 1, 2, 4, 7, and 14 days after trabeculoplasty. Flare increase after argon laser trabeculoplasty was completely blocked by 0.1% topical diclofenac and the mean of maximal flare increases was reduced significantly in the diclofenac group. Therefore, 0.1% diclofenac drops represent a very efficient anti-inflammatory therapy after argon laser trabeculoplasty.

Alteration of human conjunctival epithelial proliferation.

We used in vitro bromodeoxyuridine to analyze the labeling indexes of conjunctival cells in several external eye diseases. Patients with superior limbic keratoconjunctivitis, squamous cell carcinoma of the conjunctiva, drug-induced pseudopemphigoid, and Stevens-Johnson syndrome had increased conjunctival DNA synthesis.

Indocyanine green angiographic features in posterior scleritis.

PURPOSE: To determine choroidal involvement in posterior scleritis by examining indocyanine green angiographic features. METHODS: Indocyanine green angiography was performed according to a standard uveitis angiographic protocol in eight consecutive patients with posterior scleritis. Indocyanine green angiography data were compared to fundus color photographs, red-free photographs, and fluorescein angiography. RESULTS: The principal indocyanine green angiographic feature was diffuse zonal choroidal indocyanine green hyperfluorescence in the intermediate (+/-10 minutes) and late (+/-40 minutes) phases of angiography present in all eight patients who regressed in response to anti-inflammatory therapy. In four patients (two with massive subretinal exudation), additional fluorescing pinpoints were present in the zonal hyperfluorescent areas. Additional features included irregular delayed choroidal perfusion (five of eight patients)--irregularly distributed dark dots that were present up to the intermediate phase and becoming isofluorescent in the late phase that gave a mottled aspect to the choroid--and enlargement of draining choroidal veins. In bilateral patients, clinical features and indocyanine green angiography signs were roughly symmetric. CONCLUSIONS: In posterior scleritis, indocyanine green angiography allowed us to identify areas of choroidal hyperfluorescence, possibly indicating areas of maximal inflammatory activity, and demonstrated regression of hyperfluorescence in response to therapy. Indocyanine green angiography was useful in assessing the extent of choroidal involvement and will probably serve as one of the follow-up parameters for disease evolution and response to therapy.

Indocyanine green angiographic features in tuberculous chorioretinitis.

PURPOSE: To determine choroidal involvement in presumed tuberculous posterior uveitis by examining indocyanine green angiographic features. METHODS: Indocyanine green angiography was performed according to a standard uveitis angiographic protocol in eight consecutive patients (15 eyes) with presumed posterior tuberculous uveitis. RESULTS: In 100% of the 15 examined eyes, indocyanine green angiography disclosed choroidal lesions that were subclinical, not detected by fundus examination or fluorescein angiography, in six (40%) of 15 eyes. Findings were classified into four main angiographic signs: (1) irregularly distributed, hypofluorescent areas in the early and intermediate phases of angiography that either became isofluorescent (type 1 hypofluorescence) or remained hypofluorescent (type 2 hypofluorescence) in the late phase; (2) numerous, small, focal, hyperfluorescent spots; (3) choroidal vessels that appeared fuzzy in the intermediate phase because of leakage, leading in the late phase to (4) diffuse choroidal hyperfluorescence. Type 1 hypofluorescent lesions, fuzzy choroidal vessels, and diffuse choroidal hyperfluorescence tended to regress after the initiation of antituberculous and corticosteroid treatment. Focal hyperfluorescence tended to be associated with longstanding disease. CONCLUSIONS: Indocyanine green angiography was useful in assessing and quantifying the as yet unknown extent of choroidal involvement in tuberculous posterior uveitis. Its characteristic appearance may be a valuable contribution to the diagnosis and monitoring of treatment response.

Toxoplasmic retinochoroiditis: new insights provided by indocyanine green angiography.

PURPOSE: To analyze features of indocyanine green angiography associated with recurrent toxoplasmic retinochoroiditis. METHODS: Indocyanine green angiography was performed according to a standard protocol and correlated with clinical signs and fluorescein angiography in 12 eyes of 12 consecutive patients with recurrent toxoplasmic retinochoroiditis. RESULTS: In 10 of 12 eyes with recurrent toxoplasmic retinochoroiditis, indocyanine green angiography showed multiple satellite dark dots not seen on fluorescein angiography or clinical examination of the fundus. CONCLUSION: Indocyanine green angiography shows that recurrent toxoplasmic retinochoroiditis is more widespread than clinically visible lesions indicate. Indocyanine green angiography is useful in assessing the extent of involvement of recurrent toxoplasmic retinochoroiditis and the evolution of lesions and might also provide insights into the pathophysiology of the disease.