Lassa Virus Targeting of Anterior Uvea and Endothelium of Cornea and Conjunctiva in Eye of Guinea Pig Model.

Lassa virus (LASV), a hemorrhagic fever virus endemic to West Africa, causes conjunctivitis in patients with acute disease. To examine ocular manifestations of LASV, we histologically examined eyes from infected guinea pigs. In fatal disease, LASV immunostaining was most prominent in the anterior uvea, especially in the filtration angle, ciliary body, and iris and in and around vessels in the bulbar conjunctiva and peripheral cornea, where it co-localized with an endothelial marker (platelet endothelial cell adhesion molecule). Antigen was primarily associated with infiltration of T-lymphocytes around vessels in the anterior uvea and with new vessel formation at the peripheral cornea. In animals that exhibited clinical signs but survived infection, eyes had little to no inflammation and no LASV immunostaining 6 weeks after infection. Overall, in this model, LASV antigen was restricted to the anterior uvea and was associated with mild chronic inflammation in animals with severe disease but was not detected in survivors.

Bilateral acute pyogenic conjunctivitis with iritis induced by unilateral topical application of bacterial peptidoglycan muramyl dipeptide in adult rabbits.

The factors responsible for the conjunctivitis and iritis associated with acute ocular infection and post enteric inflammatory disease are not fully known. The pro-inflammatory activity of unilateral topical application of muramyl dipeptide (MDP; the smallest bio-active Gram-positive and Gram-negative bacterial cell wall component) was investigated in adult rabbits. The resultant bilateral conjunctivitis/iritis and pyogenic responses were characterized. Bilateral symptoms were graded by slit lamp examinations; tear fluid, Schirmer tests (tear production), blood and aqueous humor (AH) samples were obtained from MDP-treated and untreated rabbits. MDP concentration, gamma-glutamyltranspeptidase activity (GGT; key enzyme in glutathione recapture, xenobiotic detoxification, eicosanoid synthesis and neutrophil function), protein concentration, and tear cell density, cytology, and immunofluorescent antibody reactivity to GGT and calreticulin (CRT; MDP-binding protein) were determined. MDP was cleared from ipsilateral tears and serum by 6 h, but was undetected in mock-treated contralateral tears. Bilateral signs of acute transient pyogenic conjunctivitis, characterized by tearing, lid edema, conjunctival hyperemia, chemosis and leukocytic infiltrate with iritis (erythema and aqueous flare) were detected. Milder symptoms occurred in the mock-treated contralateral eyes. Bilateral symptoms, tear production, tear protein, GGT activity, and mucopurulent discharge (containing up to 2.5-5.0 × 10(6) cells/mL) were elevated 4-8 h post MDP and resolved to near pre-treatment levels by 24 h. Tear GGT activity and protein levels were higher in MDP-treated and mock-treated contralateral eyes than in eyes of untreated adult rabbits (p's < 0.001). Elevated tear GGT activity was associated with histopathology and increased vascular and epithelial permeability to serum protein, GGT-positive epithelia cells, macrophages and heterophils. Repeat MDP applications induced recurrent induction and resolution patterns of bilateral conjunctivitis/iritis and tear GGT activity, but ipsilateral GGT responses were lower. The results suggest unilateral topical MDP application to adult rabbit eyes induces a bilateral acute pyogenic conjunctivitis/iritis (PCI) characterized by increased vascular and epithelial permeability similar to acute bacterial conjunctivitis in man. The detection of CRT/GGT positive heterophils in tears suggests efferocytosis (phagocytosis of dead/dying cells). Tear GGT activity may be a useful means to quantify MDP-induced toxicity and extraocular inflammation.

[Hypopyon]. / Hipopionul.

The hypopyon represents an anterior chamber exudative syndrome which has important clinical and prognostic implications. It is very important to be able to differentiate between the sterile and infectiouos hypopyon and also to separate it by pseudohypopyon. A clear view over the etiology is strongly correlated with the therapeutical approach and the patient evolution.

Novel molecular imaging approach for subclinical detection of iritis and evaluation of therapeutic success.

There is an urgent need for early diagnosis in medicine, whereupon effective treatments could prevent irreversible tissue damage. Acute anterior chamber inflammation is the most common form of uveitis and a major cause of vision loss. The proximity of the iris vasculature to the light-permeable cornea and its involvement in ocular inflammation make it an ideal target for noninvasive molecular imaging. To accomplish this, carboxylated fluorescent microspheres (MSs) were conjugated with recombinant P-selectin glycoprotein ligand-1 and systemically injected in endotoxin-induced uveitic animals. MS adhesion in the microcirculation of the anterior and posterior chamber was visualized by intravital microscopy and scanning laser ophthalmoscopy. In iritic animals, significantly higher numbers of recombinant P-selectin glycoprotein ligand-1-conjugated MSs adhered to the endothelium (P = 0.03) matching the increase in leukocyte adhesion. Conjugated MSs specifically interacted with firmly adhering leukocytes, allowing quantification of the endogenous immune response. Topical eye drop treatment with dexamethasone (P < 0.01) or cyclosporine A (P < 0.01) significantly lowered MS adhesion in iris vessels. Surprisingly, topical dexamethasone significantly reduced MS interaction in the fundus vessels (P < 0.01), while cyclosporine A did not. In vivo MS accumulation preceded clinical signs of anterior uveitis and leukocyte adhesion in iris vasculature. This work introduces noninvasive subclinical detection of endothelial injury in the iris vasculature, providing a unique opportunity for quantifying vascular injury and immune response in vivo.

[Postoperative Candida Iris nodules: report of a case]. / Nodules iriens postopératoires à candida: à propos d'un cas.

PURPOSE: Description of an uncommon case of postoperative Candida iris nodules. CASE REPORT: A 70-year-old immunocompetent patient developed whitish iris nodules after phacoemulsification in the left eye, without any other signs of endophthalmitis. Histophathological examination showed spores of candida. These nodules did not respond to intracameral amphotericin B but disappeared with oral fluconazole. However, the functional outcome was poor because of persistant inflammation of the anterior segment. CONCLUSION: In the presence of postoperative iris nodules, fungal etiology must be considered.

Two cases of SAPHO syndrome accompanied by classic features of Behcet's disease and review of the literature.

We describe two patients with SAPHO (synovitis-acne-pustulosis-hyperostosis-ostitis) syndrome who presented some of the classic features of Behcet's disease. The first case is a man diagnosed as SAPHO at 74 years old. His major complaint is pain and swelling of the bilateral sterno-clavicular region for more than 14 years. Another conspicuous complication was bilateral glaucoma and episodes of iritis were recognized during the follow-up period. The second case is a 65-year-old woman, who first consulted us with right knee pain. As she had a past history of palmoplantar pustulosis and anterior chest pain, her sterile knee arthritis was diagnosed as SAPHO. She also had been suffering from recurrent oral aphthous ulceration since 6 months before visiting our hospital. Considering the clinical courses of our two cases and a review of five previously reported cases, these conditions may imply that classic features of Behcet's disease are minor complications of SAPHO syndrome. Human leukocyte antigen typing and frequent association of sacroiliitis in our cases and in the review of the literature for SAPHO syndrome with some of the classic features of Behcet's disease may indicate this condition to be a closely related disease with seronegative spondylo-arthritis.

Bilateral ankle edema with bilateral iritis.

I report two patient presented to me with bilateral symmetrical ankle edema and bilateral acute iritis. A 42-year-old female of Indian origin and 30-year-old female from Somalia both presented with bilateral acute iritis. In the first patient, bilateral ankle edema preceded the onset of bilateral acute iritis. Bilateral ankle edema developed during the course of disease after onset of ocular symptoms in the second patient. Both patients did not suffer any significant ocular problem in the past, and on systemic examination, all clinical parameters were within normal limit. Lacrimal gland and conjunctival nodule biopsy established the final diagnosis of sarcoidosis in both cases, although the chest x-rays were normal.

Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism.

We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.

Enhanced ocular anti-inflammatory activity of ibuprofen carried by an Eudragit RS100 nanoparticle suspension.

PURPOSE: To investigate the ocular pharmacodynamic profile of a polymer nanoparticle system loaded with sodium ibuprofen (IBU-RS) in comparison to an aqueous solution of ibuprofen lysinate (IBL) in the rabbit eye both being applied topically. METHODS: Ocular inflammation was elicited by topical application of sodium arachidonate. Inflammation was quantified according to a modified Draize test. The protein level and the number of polymorphonuclear leukocytes in the aqueous humor were assessed after 2 h from arachidonate instillation. The ibuprofen concentration in the aqueous humor was evaluated by HPLC assay. The physico-chemical properties of nanoparticles were also evaluated. RESULTS: The IBU-RS nanosuspension formulation significantly reduced the primary signs of ocular inflammation as well as significantly reducing the protein level and the number of polymorphonuclear leukocytes in the aqueous humor compared with the IBL formulation. Furthermore, the aqueous humor drug concentration from the group treated with IBU-RS was significantly higher compared to the IBL-treated group. The IBU-RS nanosuspensions showed very interesting size and surface charge values, adequate for ophthalmic administration. CONCLUSIONS: The pharmacological profile of the topical IBU-RS nanosuspension formulation described in this study indicates that the dispersion of the drug within RS polymer nanoparticles increased its ocular bioavailability and ultimately its pharmacological activity.

Effects of enzymatic sterilization detergents on the corneal endothelium.

OBJECTIVE: To evaluate the potential of enzymatic detergents to cause endothelial damage and anterior segment inflammation. METHODS: Paired rabbit corneas were mounted in an in vitro specular microscope. Endothelia were perfused either with the sterile irrigating solution BSS Plus (Alcon Laboratories Inc, Ft Worth, Tex) (control) or 0.1%, 0.4%, or 1.0% Medline Enzymatic Detergent (Medline Industries Inc, Mundelein, Ill) in BSS Plus. Swelling rates were determined by regression analysis. Human endothelia were perfused using 1.56% detergent. All corneas were fixed for scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Endothelial permeability was determined following perfusion of 0.78% detergent. Finally, in vivo intracameral injections with 1.56% or 3.9% detergent were performed to evaluate clinical changes and to correlate with histopathologic analysis. RESULTS: Dose-related corneal swelling rates were observed. Digital specular micrographs revealed greater endothelial cell damage when perfused with 1.0% detergent. The TEM of endothelia exposed to 1.0% solutions demonstrated abnormal vacuolization and dilated extracellular spaces, which manifested as an increased corneal permeability to 3 to 4 times that of controls. Human corneas swelled comparably to rabbit corneas but demonstrated increased sensitivity when evaluated by TEM and SEM. Histopathologic analysis after intracameral injection revealed thickened corneas with fewer endothelial cells and irises with increased inflammatory and fibrinous responses compared with controls. CONCLUSIONS: Medline Enzymatic Detergent causes a dose-dependent corneal swelling, ultrastructural damage, increased corneal permeability, and increased inflammatory response in the iris after intracameral injection. CLINICAL RELEVANCE: Failure to adequately rinse the detergent from surgical instruments may result in corneal edema and intraocular inflammation.

Blockage of complement regulators in the conjunctiva and within the eye leads to massive inflammation and iritis.

The open environment of the eye is continuously subject to an influx of foreign agents that can activate complement. Decay-accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 are regulators that protect self-cells from autologous complement activation on their surfaces. They are expressed in the eye at unusually high levels but their physiological importance in this site is unstudied. In the rat, a structural analogue termed 5I2 antigen (5I2 Ag) has actions overlapping DAF and MCP. In this investigation, we injected F(ab')2 fragments of 5I2 mAb into the conjunctiva and aqueous humor, in the latter case with and without concomitant blockage of CD59. Massive neutrophilic infiltration of the stroma and iris resulted upon blocking 5I2 Ag activity. Frank necrosis of the iris occurred upon concomitant intraocular blockage of CD59. C3b was identified immunohistochemically, and minimal effects were seen in complement-depleted animals and in those treated with non-relevant antibody. The finding that blockage of 5I2 Ag function in periocular tissues and within the eye causes intense conjunctival inflammation and iritis demonstrates the importance of intrinsic complement regulators in protecting ocular tissues from spontaneous or bystander attack by autologous complement.

Long-term posterior and anterior segment complications of immune recovery uveitis associated with cytomegalovirus retinitis.

PURPOSE: To identify and describe long-term posterior and anterior segment complications of immune recovery uveitis in patients with inactive cytomegalovirus retinitis who are undergoing highly active antiretroviral therapy-mediated recovery of immune function. METHODS: A prospective cohort study at a university medical center. Twenty-nine eyes of 21 patients with immune recovery uveitis and inactive cytomegalovirus retinitis were followed for 14.5 to 116 weeks (median, 43 weeks) after diagnosis of immune recovery uveitis. RESULTS: Nine eyes of nine patients developed visually important complications involving the posterior segment, anterior segment, or a combination of both. Posterior segment complications included severe proliferative vitreoretinopathy in three eyes and spontaneous vitreous hemorrhage from avulsion of a blood vessel secondary to contraction of the inflamed vitreous in one eye. Proliferative vitreoretinopathy recurred in all cases after surgery, severely compromising the visual outcome. Anterior segment complications included posterior subcapsular cataracts with vision decrease in five eyes and persistent anterior chamber inflammation after cataract extraction, resulting in posterior synechiae and large visually important lens deposits in three eyes. CONCLUSION: Persistent inflammation in immune recovery uveitis may lead to vision-threatening complications, such as proliferative vitreoretinopathy, posterior subcapsular cataracts, and severe postoperative inflammation. Immune recovery uveitis is a chronic inflammatory syndrome that may result in complications months to years after the onset of inflammation.

Effects of nilvadipine, nicardipine and verapamil on acute rise of aqueous flare induced by iris photocoagulation or intravenous lipopolysaccharides in pigmented rabbits.

The effects of nilvadipine, nicardipine and verapamil on the acute rise of aqueous flare induced by argon laser photocoagulation of the iris or by intravenous injection of lipopolysaccharides (LPS, 0.5 microg/kg) were investigated in pigmented rabbits. Nilvadipine, nicardipine and verapamil were injected intravenously. Aqueous flare was measured with a laser flare cell meter. Following photocoagulation, aqueous flare increased, reached its maximum at 45-75 min and then decreased. After administration of LPS, aqueous flare increased, reached its maximum at 4 h and then returned to baseline levels at about 24 h. Flare reactions were inhibited by nilvadipine in a dose-dependent manner. The elevations were maximally inhibited by nilvadipine 30 min before photocoagulation or intravenous LPS. Two hundred micrograms per kilogram of nilvadipine inhibited 81% of photocoagulation-induced flare elevation, while the same dose of nicardipine and verapamil inhibited 19 and 9% of the elevation, respectively. The same dose of nilvadipine inhibited 51% of LPS-induced flare elevation, while the same dose of nicardipine and verapamil inhibited 6 and 4% of the elevation, respectively. In conclusion, nilvadipine inhibited the experimental elevation of aqueous flare more effectively than did nicardipine and verapamil.

Confocal microscopy in the iridocorneal endothelial syndrome.

AIMS: To report the appearances of iridocorneal endothelial (ICE) syndrome from real time, white light confocal microscopy. METHODS: Three consecutive patients, each with ICE syndrome, were examined prospectively. Corneal specular and confocal microscopic examinations were performed in all three patients. In the first patient, a penetrating keratoplasty was performed and the cornea was examined by light and scanning electron microscopy. No surgery was performed in the remaining two patients. RESULTS: In the first patient corneal oedema prevented endothelial specular microscopy. Confocal microscopy performed before penetrating keratoplasty successfully revealed abnormal epithelial-like endothelial cells. Histological examinations of the cornea following penetrating keratoplasty revealed the presence of multilayered endothelial cells with epithelial features (microvilli). In the remaining two patients, specular microscopy showed the presence of ICE cells with typical dark/light reversal. Confocal microscopy demonstrated groups of endothelial cells with epitheloid appearances. In all three patients, the contralateral endothelial appearance was normal by specular and confocal microscopy, except for moderate endothelial polymegathism in one patient. Epithelial-like endothelial cells were characterised by prominent nuclei on confocal microscopy. CONCLUSIONS: The application of confocal microscopy indicates that the ICE syndrome is characterised by epitheloid changes in the endothelium. Confocal microscopy may be used to diagnose the ICE syndrome by demonstrating epithelial-like endothelial cells with hyperreflective nuclei. This technique is especially of value in cases of corneal oedema, since specular microscopy may fail to image the endothelium in such cases.

Expression of stress-response protein 60 in iritis associated with experimental autoimmune encephalomyelitis.

PURPOSE: To study the expression of stress-response proteins in the inflamed iris of rats with experimental autoimmune encephalomyelitis (EAE). METHODS: EAE was induced in Lewis rats by immunization with homogenized spinal cord of the guinea pig emulsified in complete Freund's adjuvant (CFA) (group EAE). Control rats included those immunized with only CFA (group CFA) and those that were untreated (group Normal). Immunohistochemical study for the localization of stress-response protein (srp) 27, srp 60, srp 72, ubiquitin, and alphaB-crystallin was performed. RESULTS: All rats in group EAE developed iritis, whereas none of the rats in group CFA and group Normal developed iritis. No expression of ubiquitin, alphaB-crystallin, srp 27, srp 60, or srp 72 was seen in the epithelium of the iris in group CFA rats. In the eyes of rats in group EAE, srp 60 was expressed in the epithelium of the iris in 20 of 22 (90.9%), ubiquitin in 4 of 22 (18.2%), and alphaB-crystallin in 3 of 22 (13.6%). In the group Normal rats, only ubiquitin was expressed in the epithelium of the iris in 1 of 6 (16.7%) eyes examined. CONCLUSIONS: These results suggest that srp 60 may be a potential uveitogenic antigen in the iris in EAE.

Cytomegalovirus iritis.

We describe a case of focal cytomegalovirus iritis in a patient with acquired immunodeficiency syndrome (AIDS) who had CMV retinitis. The autopsy showed histologic evidence of focal iritis in the left eye. This iritis was characterized by infiltration of acute inflammatory cells mixed with cytomegalic cells, which was confirmed by CMV-specific immunohistochemical staining. The case suggested that cytomegalovirus could be a direct causative agent of infectious iritis in AIDS patients.

Serous detachment of the ciliary body in Harada disease.

PURPOSE: To evaluate the involvement of the anterior ocular segment in Harada disease. METHODS: In a prospective study, ultrasound biomicroscopy was performed in 18 consecutive eyes of nine patients with Harada disease in its acute phase before and after onset of systemic corticosteroid therapy. Examination was repeated every 3 days until the resolution of serous retinal detachment. RESULTS: Serous detachment of the ciliary body was present in 11 (61%) of 18 eyes before treatment. The circumference of the ciliary body was detached in 10 of the 11 eyes. The height of ciliary detachment ranged from 20% to 250% of the scleral thickness. Ciliary detachment was more prominent in eyes with more extensive retinal detachment. There was no relation between the frequency of ciliary detachment and the severity of iritis. On day 3 of treatment, ciliary detachment had disappeared in seven eyes. In the other four eyes, it diminished in height to less than 10% of scleral thickness. Retinal detachment disappeared on days 6 through 17 (mean, day 11) of treatment. Two eyes of one patient showed very shallow anterior chambers. These eyes showed high ciliary detachment at 250% of scleral thickness. In another patient, both eyes developed -5.0 diopters of transient myopia. CONCLUSION: Ciliary detachment was a frequent finding in the acute stage of Harada disease. Its resolution was more prompt than that of serous retinal detachment after treatment. Ciliary detachment may be related to the development of a shallow anterior chamber.