Effects of ROCK Inhibitors on Apoptosis of Corneal Endothelial Cells in CMV-Positive Posner-Schlossman Syndrome Patients.

Purpose: To examine the role of aqueous tumor necrosis factor α (TNF-α)-RhoA-Rho kinase (ROCK) signaling in cytomegalovirus (CMV)-induced apoptosis and the barrier function of cultured human corneal endothelial cells (hCECs) in CMV-positive Posner-Schlossman syndrome (CMV+/PSS) patients. Methods: Aqueous levels of TNF-α, IL-8, IL-10, and several other cytokines in 19 CMV+/PSS patients and 20 healthy control subjects were quantitated using a multiplex assay. The expression of active RhoA in hCECs post-CMV infection was determined using western blotting (WB). The expression levels of TNF-α and nuclear factor kappa B (NF-κB) in CMV-infected hCECs were examined by immunocytochemistry (ICC) and WB with and without ROCK inhibitors. The apoptotic rate and barrier integrity in CMV-infected hCECs were also examined. Results: The expression levels of TNF-α, monocyte chemoattractant protein-1 (MCP-1), IL-8, and IL-10 were upregulated in the aqueous humor of CMV+/PSS patients, and among these upregulated cytokines aqueous TNF-α was negatively correlated with the number of corneal endothelial cells. In CMV-infected hCECs, upregulation of TNF-α and NF-κB was determined by WB and ICC. In hCECs, CMV infection induced apoptosis and significantly impaired cell-cell contacts, effects that were attenuated by treatment with a ROCK inhibitor. Conclusions: Aqueous TNF-α was upregulated in CMV+/PSS patients, which may have triggered corneal endothelial cell loss. Modulation of TNF-α, including its downstream Rho-ROCK signaling, could serve as a novel treatment modality for corneal endothelial cell loss in CMV+/PSS patients.

Analysis of retinal microvasculature in Fuchs' uveitis syndrome. Retinal microvasculature in Fuchs' uveitis.

PURPOSE: The objective of this study is to quantitatively analyse the foveal microvasculature in eyes with Fuchs' Uveitic Syndrome (FUS), or Fuchs' Heterochromic Iridocyclitis (FHI), by Optical coherence tomography angiography (OCTA). METHODS: Thirty patients with FUS and 30 healthy volunteer patients (control group) were enrolled in the study. Vascular density (VD) in the superior and deep capillary plexuses (SCP, DCP) were reported and compared between eyes with FUS (FU), fellow eyes (FE) and the control group. RESULTS: Foveal VD and parafoveal VDs in all quadrants of the SCP were significantly lower in the FU group than the FE group and normal eyes (P<0.05). Foveal VDs in the DCP were similar between the three groups (P>0.05); however, parafoveal VDs in all quadrants of the DCP were significantly lower in the FU group than in the FE and control eyes (P<0.05). Foveal and parafoveal VDs in both the SCP and DCP were similar between fellow eyes and the control group. CONCLUSION: Fuchs' Uveitic Syndrome (Fuchs' Heterochromic Iridocyclitis) affects not only the anterior uvea and vitreous but also the retinal microvasculature. Analysis by OCT-A may enable us to understand the extent of this disease.

Isolated oculocutaneous sarcoidosis in a teenage male: a rare case report.

Sarcoidosis is an inflammatory disease with multisystem involvement characterized by the presence of noncaseating granulomas. It can affect virtually every organ of the body, with lung involvement being most common occurring in >90% of patients. Other organs affected are skin, eye and liver. Skin involvement is common, affecting 25-35%. Here we present a rare case of a 15 year-old male with isolated oculocutaneous sarcoidosis without systemic involvement.

Anterior Segment Characteristics of Fuchs Uveitis Syndrome.

PURPOSE: To evaluate the differences in the biometric parameters of the anterior segment in Fuchs' uveitis syndrome (FUS). METHODS: 30 eyes of 15 consecutive patients with unilateral FUS were examined. Anterior segment parameters were measured by rotating Scheimpflug imaging camera. Central endothelial cell count was measured by noncontact specular microscopy. RESULTS: The central cornea was thinner (p < 0.001), the iridocorneal angle was significantly larger (p < 0.010), anterior chamber depth was deeper in the eyes with FUS (p < 0.006). The iris bowing was different between the affected eye and the healthy eye. The mean endothelial cell density of eyes with FUS was significantly lower than control eyes (p < 0.001). CONCLUSIONS: Scheimpflug imaging method is a useful tool to analyze the anterior segment parameters in FUS. Endothelial cell loss, as well as decreased percentage of endothelial hexagonal cells, is obtained by noncontact specular microscopy in patients with FUS.

Clinical, histopathological and immunohistochemical characterization of a novel equine ocular disorder: heterochromic iridocyclitis with secondary keratitis in adult horses.

OBJECTIVE: To describe the clinical, histopathologic and immunohistochemical characteristics of an equine ocular inflammatory disease resulting in anterior uveitis and corneal endothelial inflammation associated with iris pigment dispersion and retrocorneal fibrous membrane (RFM) formation. DESIGN: Retrospective study. ANIMALS STUDIED: Sixteen horses with evidence of pigmented keratic precipitates (KPs), corneal edema, and/or iris depigmentation. Information collected from the medical records included signalment, clinical signs, prereferral treatment duration and response to therapy, ophthalmic examination findings, postreferral treatment, response to therapy, and outcome. RESULTS: Twenty-one eyes from 16 horses were affected. Age ranged between 9 and 25 years (Average 16.1 years). Blepharospasm, epiphora, and/or corneal opacification were the first clinical signs noted. At the time of referral pigmented KPs, corneal edema, iridal depigmentation, and retrocorneal membranes were commonly seen. Treatment included topical and/or systemic anti-inflammatories and antibiotics with variable response. Reduction or cessation of anti-inflammatory therapy resulted in worsening of clinical signs and disease progression. Eight eyes ultimately required enucleation. Histopathology changes include iridal pigment loss and dispersion, RFM formation, and keratitis. Variable degrees of lymphoplasmacytic inflammation were dominated by T-cells within the corneal stroma, RFM, iris, and ciliary body with occasional multinucleated giant cells. CONCLUSIONS: Heterochromic iridocyclitis with secondary keratitis (HIK) is characterized by uveal inflammation with pigment dispersion and suspected corneal endothelial dysfunction. Horses being treated for HIK require diligent and frequent follow-up examinations in combination with aggressive local immune suppression to control the disease. However, HIK may not respond to therapy and enucleation may ultimately be required to ensure the horse's comfort.

[Post-operational acute iridocyclitis and immune shifts in intraocular humor of patients with cataracts].

The negative tendency of cataracts growth, which is a consequence of various diseases of the organism including those of eyes, combined in the concept "the complicated cataract" is clearly traced now. In the concept of such a complication of cataracts as the acute autoimmune iridocyclitis, the important role, in our opinion, should be given to regional immunopathological disorders, which testify to the withdrawal of the known phenomenon underlying in the immunological tolerance of post-barrier eye membrane "a syndrome of eye anterior chamber-associated immune deviation (ACAID). Microcoaxial phacoemulsification was carried in three hundred patients with senile and complicated cataracts. The intraocular humor of the operated patients was subjected to immune-enzyme immunomorphological analysis for СD4, СD8, IgG and B-lymphocytic populations. On the base of performed clinical-laboratory research we found that the gravest inflammatory process in eye tissues manifested in the form of autoimmune aseptic iridocyclitis was observed particularly in patients with complicated cataracts, proceeding on the background of glaucoma, diabetes and the previous trauma of an eye. The high indicators of IgG, СD4 were registered on the background of low СD8 indicators in the intraocular humour at these patients. The revealed regional inflammatory reaction in eye tissues testifies, in our opinion, in favour of in situ withdrawal of ACAID; this latter brings to origination of acute aseptic autoimmune iridocyclitis in the early post-operational course of the complicated cataracts.

Fuchs' heterochromic cyclitis: a post-infectious manifestation of ocular toxoplasmosis?

The purpose of this article is to report the development of Fuchs' heterochromic cyclitis (FHC) secondary to toxoplasmosis chorioretinitis. The design is based on observational case series report. We report in this article six cases of typical FHC developing secondary to ocular toxoplasmosis. Intraocular immunoglobulin G production against Toxoplasma gondii was determined in the aqueous humor of five patients by calculation of the Goldmann-Witmer coefficient (GWC). The clinical examination revealed typical FHC with no active chorioretinal scar. We report on five women and one man (aged 33-64 years old; median 44.6 years) who developed FHC over a period of time ranging from 2-13 years. A positive GWC (>3) was found in four patients; of the two remaining patients one was negative and the other did not have anterior chamber paracentesis. Four patients were treated for an active ocular toxoplasmic lesion before the development of FHC with pyrimethamine, sulfadiazine and corticosteroids. Two patients had negative anti-toxoplasmic therapy for FHC (one with trimethoprim-sulfamethoxazole for 3 weeks and the other with pyrimethamine, sulfadiazine and corticosteroids for 8 weeks). One never had any treatment. All the patients had mild anterior chamber reaction with no synechia, diffuse and characteristic white stellate keratic precipitates and vitritis; five patients had posterior subcapsular cataract and heterochromia and three had elevated intraocular pressure. The findings help us to conclude that FHC can develop over a period of time after ocular toxoplasmosis. This could be a main association to search for when a Fuchs' uveitis is found with a chorioretinal scar. Ocular inflammation does not mean reactivation of ocular toxoplasmosis. FHC could be a secondary immune reaction with a past antigenic stimulation to a previous infection, i.e., toxoplasmosis, etc.

Chikungunya virus iridocyclitis in Fuchs' heterochromic iridocyclitis.

We are reporting a case of bilateral Fuchs' heterochromic iridocyclitis with chikungunya virus infection in the left eye. A 20-year-old female was presented with a past history of fever suggestive of chikungunya with bilateral Fuchs' heterochromic iridocyclitis and complicated cataract. She had a tripod dendritic pattern of keratic precipitates by confocal microscopy in the left eye with a stippled pattern of keratic precipitates in both eyes. The real-time polymerase chain reaction (RT-PCR) assay in the aqueous humor detected 98 copies/ml of chikungunya virus RNA. The patient underwent clear corneal phacoemulsification with in-the-bag intraocular lens implantation in the left eye with a good visual outcome. This is the first report where the presence of chikungunya virus RNA has been associated with a case of bilateral Fuchs' heterochromic iridocyclitis.

[Ocular leprosy: a historical approach]. / Hanseníase ocular: uma abordagem histórica.

A sharp drop in the prevalence of leprosy occurred in the last three decades. However, the incidence has not decreased at the same rate. Three years after the World Health Organization last deadline for leprosy control, patients considered healed still need special care for their incapacities and immunopathological reactions. Medical literature reffers blindness in 4% to 11% of studied patients and more than 20% with severe visual problems due to corneal exposure, bacillary invasion and hipersensibility. These mechanisms result in a population of nearly one million blind leprosy patients even though official prevalence accounts no more than 250,000 patients worldwide. The author calls for better patients management and follow-up and urges ophthalmologists to become more aware and interested in the treatment of the ocular complications of leprosy.

Hanseníase ocular: uma abordagem histórica / Ocular leprosy: a historical approach

Houve uma acentuada queda na prevalência da hanseníase nas últimas três décadas. Contudo, a incidência não diminuiu na mesma proporção. Hoje, três anos após a última data estipulada pela Organização Mundial da Saúde para o controle da hanseníase, pacientes considerados curados ainda necessitam de cuidados especiais por causa de suas incapacidades e reações imunológicas. A literatura médica refere cegueira em 4 por cento a 11 por cento dos pacientes estudados e, mais de 20 por cento com graves problemas visuais devido a exposição da córnea, invasão bacilar e hipersensibilidade; estes mecanismos resultam em uma população de aproximadamente 1 milhão de pacientes cegos, embora a prevalência oficial não passe de 250.000 pacientes em todo o mundo. O autor destaca a necessidade de melhor tratamento e acompanhamento dos pacientes e, conclama os oftalmologistas a tornarem-se mais perceptivos e se interessarem mais pelo tratamento das complicações oculares da hanseníase.

A sharp drop in the prevalence of leprosy occurred in the last three decades. However, the incidence has not decreased at the same rate. Three years after the World Health Organization last deadline for leprosy control, patients considered healed still need special care for their incapacities and immunopathological reactions. Medical literature reffers blindness in 4 percent to 11 percent of studied patients and more than 20 percent with severe visual problems due to corneal exposure, bacillary invasion and hipersensibility. These mechanisms result in a population of nearly one million blind leprosy patients even though official prevalence accounts no more than 250,000 patients worldwide. The author calls for better patients management and follow-up and urges ophthalmologists to become more aware and interested in the treatment of the ocular complications of leprosy.

Evaluation of keratic precipitates and corneal endothelium in Fuchs' heterochromic cyclitis by in vivo confocal microscopy.

PURPOSE: To analyse keratic precipitates in Fuchs' heterochromic cyclitis (FHC) by in-vivo confocal microscopy (IVCM). PATIENTS AND METHODS: A retrospective chart review of 13 consecutive patients with FHC was conducted. Data collection included medical and ophthalmological history, age, age at diagnosis, gender, detailed slit-lamp examination and IVCM images. The IVCM characteristics of keratic precipitates and of the endothelium were analysed. RESULTS: Large hyperreflective deposits corresponding to keratic precipitates were observed on the endothelium of all FHC eyes and showed a great consistency among the different patients. These infiltrating keratic precipitates had a dendritic shape, with a small central core with numerous thin pseudopodia sometimes making connection between different keratic precipitates. The mean density of these keratic precipitates was 16.01/mm(2) (SD 6.54). The mean size of the largest dimension of these keratic precipitates was 127.31 microm (SD 41.49; range 66.16-201.4 microm). Hyporeflective round defects were observed at the level of the endothelium at contact or in the close vicinity of keratic precipitates or smaller hyperreflective deposits. All contralateral (non-affected eyes) had no keratic precipitates nor endothelial abnormalities. CONCLUSIONS: By providing high resolution images of corneal endothelium and keratic precipitates, IVCM could help the diagnosis and understanding of complex forms of intraocular inflammation such as FHC.

Aqueous flare and cells in Fuchs syndrome.

PURPOSE: To quantitatively evaluate aqueous flare and cells in patients with Fuchs syndrome. METHODS: The medical records of 40 patients (47 eyes) diagnosed with Fuchs syndrome between February 2006 and January 2007 at the Uveitis Study Center of Sun Yat-sen University were retrospectively reviewed. Aqueous flare and cells were clinically evaluated and quantified with laser flare-cell meter. Statistical analysis was performed to investigate the relationship between flare values and cell counts, and clinical parameters including patients' age, sex, duration of disease, best-corrected visual acuity, keratic precipitate, iris depigmentation, intraocular pressure, and posterior subcapsular lens opacities. RESULTS: Aqueous flare values (photon counts/ms) were significantly higher in Fuchs syndrome (9.40+/-5.85) than in normal controls (5.77+/-1.89, P=0.000). Aqueous cell counts (cells/0.5 mm(3)) were also significantly higher in Fuchs syndrome (5.09+/-4.84) than in normal controls (1.14+/-1.03, P=0.000). The flare values were positively correlated with the cell counts (r=0.331, P=0.001). Both flare values and cell counts were higher in eyes with keratic precipitates scored 2+ or 3+ as compared to those with a 1+ score. Higher flare values and cell counts were also observed in eyes with a 2+ or 3+ iris depigmentation score as compared to those with a 1+ score. No difference was found between flare values and cell counts and other parameters. CONCLUSION: Breakdown of blood-aqueous barriers and increased cell counts are present in the affected eyes in patients with Fuchs syndrome. These changes are positively associated with the degree of keratic precipitates and iris depigmentation.

The efficacy of intravitreal vancomycin and dexamethasone in the treatment of experimental bacillus cereus endophthalmitis.

PURPOSE: Bacillus cereus causes the most virulent and refractory form of endophthalmitis. The authors analyzed effectiveness of intravitreal vancomycin with or without dexamethasone for experimental Bacillus cereus endophthalmitis. METHODS: Rabbit eyes were injected intravitreally with 1x10(6) colony-forming units of Bacillus cereus organisms. At 24 hours after injection, eyes were injected intravitreally with 0.1 ml of balanced salt solution (group 1, n=10), 1 mg vancomycin (group 2, n=10), and antibiotic plus 0.4 mg dexamethasone (group 3, n=10). Inflammatory scores were assessed 7 days and 14 days after treatment. Furthermore, histologic grading was carried out at the conclusion of the clinical observations. RESULTS: Eyes treated with vancomycin, with or without dexamethasone at 7 days and 14 days expressed significant less inflammation over iris and vitreous than the control group (p<0.05). Moreover, eyes treated with vancomycin with dexamethasone showed less inflammation over the conjunctiva and vitreous at 7 days and over the iris and vitreous at 14 days, compared to antibiotic treatment alone (p<0.05). Additionally, at 14 days, the histopathological changes of eyes treated with vancomycin with dexamethasone had less conjunctival inflammation, mild iridocyclitis, less vitreous cells, and less choroidal vasculitis and retinitis compared to control group and antibiotic treatment alone, respectively (p<0.05). CONCLUSION: Intravitreal injection of vancomycin improved the therapeutic outcome of Bacillus cereus endophthalmitis. The addition of dexamethasone to antibiotic treatment provided a therapeutic benefit over antibiotic alone.

Fuchs' heterochromic uveitis: a longitudinal clinical study.

PURPOSE: To carry out a longitudinal study of patients with Fuchs' heterochromic uveitis (FHU) in western Sweden and to establish the factors responsible for diagnostic delay. METHODS: A sample of 54 patients, 51 with monocular and three with binocular FHU, were followed for periods ranging from 8 months to 15 years. Firm diagnostic criteria were set. A detailed anamnesis regarding ocular and extraocular symptoms was taken. The eyes were repeatedly examined. Toxoplasma serology was analysed. Complications were noted. RESULTS: The delay between the first visit to an ophthalmologist and diagnosis was 0-26 years. The most common first symptom was floaters. Iris heterochromia was absent in 11 patients and discrete in 26. Iris atrophy (a diagnostic criterion) was easy to miss. Chorioretinal scars were found in six patients. Toxoplasma serology was positive in 18 (35%) patients. The only serious complication was glaucoma. CONCLUSIONS: The most important reason for delay in diagnosis of FHU is, in our opinion, failure to consider the disease as a diagnosis. This failure may occur because heterochromia is often missing or discrete, iris atrophy is easily overlooked, and vitreous opacities are common, often cause early symptoms and can explain prolonged workup and therapy. A connection with toxoplasmosis in individual cases cannot be excluded but toxoplasmosis cannot be considered a major aetiological factor. If detailed anamnesis is negative and diagnostic criteria are fulfilled, no further workup is required.

Aproximación diagnóstica a la ciclitis heterocrómica de Fuchs en ausencia de heterocromía / Fuchs´heterochronic cyclits without heterochromia: a diagnostic approach

Objetivo: Obtener pautas de diagnóstico de la ciclitis heterocrómica de Fuchs (CHF) en ausencia de heterocromía utilizando metodología bayesiana. Métodos: Se obtienen las probabilidades pre-test y post-test de que un determinado paciente sin heterocromía pero con otros síntomas característicos de la enfermedad, tales como nódulos iridianos, cataratas, glaucoma o vitritis anterior, tenga CHF. Para ello se utiliza el teorema de Bayes para la probabilidad condicionada. Los valores de la prevalencia de la CHF y de la frecuencia de presentación de los síntomas en la CHF y en el total de las uveitis anteriores se obtienen de los datos de la literatura publicada. Resultados: En ausencia de heterocromía, la combinación de nódulos iridianos junto con cataratas, vitritis o glaucoma, así como la asociación de estos tres últimos síntomas aún sin nódulos supone una probabilidad acumulada de más del 50% de tener la enfermedad. Conclusiones: La coincidencia en un paciente de varios síntomas indicativos aún en ausencia de heterocromía puede hacer que la CHF sea una opción diagnóstica probable

Objective: To obtain diagnostic guidelines of Fuchs’ heterochromic cyclitis (FHC) in the absence of heterochromia using Bayesian methods. Methods: The pre-test and post-test likelihood that a certain patient without heterochromia (but with other characteristic symptoms of the disease such as iris nodules, cataracts, glaucoma or vitritis) has FCH, was assessed by the Bayes’ theorem for conditioned likelihood. The prevalence values of FCH and the presentation rate of symptoms in FCH and in other forms of anterior uveitis were obtained from published literature data. Results: In the absence of heterochromia, the combination of iris nodules together with cataracts, vitritis or glaucoma, and the association of the last three symptoms in the absence of nodules, resulted in an accumulated likelihood of more than 50% of subjects having the disease. Conclusions: The coincidence in one patient of several indicative symptoms, even in the absence of heterochromia, may make FCH a likely diagnostic option

Topographic optic disc analysis by Heidelberg retinal tomography in ocular Behcet's disease.

AIM: To compare the topographic characteristics of the optic discs in patients with severe and mild ocular Behçet's disease by using Heidelberg retinal tomographaphy (HRT). METHODS: This prospective study included 47 eyes of 47 patients with ocular BD who were being followed-up at the Uveitis Clinic of the Ankara Ulucanlar Eye Research Hospital, Ankara, Turkey. The patients were divided into two groups. Group 1 consisted of 21 eyes with mild uveitis, and group 2 consisted of 26 eyes with severe uveitis. All patients underwent topographic optic disc analysis by HRT II, and the quantitative optic disc parameters of both groups were compared by non-parametric Mann-Whitney U test. RESULTS: The mean cup volume, rim volume, cup area, disc area and cup depth in group 1 were found to be statistically significantly greater than those in group 2 (p<0.0001, p = 0.03, p = 0.021, p = 0.01 and p = 0.017, respectively), while the difference between the mean cup-to-disc ratios in group 1 and group 2 were found to be statistically insignificant (p = 0.148). CONCLUSION: A relationship was found between the severity of ocular BD and optic disc topography determined by HRT. In eyes with smaller optic discs, uveitis was observed to have a more severe course with more frequent relapses than those with larger discs.

Skin burn, bilateral iridocyclitis and amnesia following a lightning injury.

PURPOSE: To describe a case of lightning injury restricted to the eyes and facial skin. METHODS: Case history describing the clinical examination of a 54-year-old woman. RESULTS: Following a lightning stroke the patient suffered from a sharply demarcated facial skin burn and bilateral iridocyclitis with raised intraocular pressure. Initially she had amnesia regarding the incident. She recovered on symptomatic treatment, with dry eyes as the only sequela. CONCLUSION: We suggest that a lightning current travelled over the outside of the patient's body facilitated by her wet raincoat, a so-called flash-over. Thereby, she was spared from more severe injury, and only the exposed areas of the face and eyes were affected.