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.

Experimental immunogenic rubeosis iridis.

We have developed a primate model of rubeosis iridis in monkeys systemically sensitized to crystalline beef insulin. After intravitreal insulin injection, the dose-related immunogenic inflammation includes cells, flare, fibrin, and blood in the anterior chamber. With more severe inflammation, posterior synechiae, iris bombé, and cataracts occur. Of particular importance, new blood vessels develop within the stroma and on the anterior surface of the iris. Following injection of small amounts of insulin, the anterior surface vessels may regress over time, and the iris regains its normal appearance and coloration. However, the new stromal vessels persist and are cuffed by inflammatory cells including plasma cells. After injection of large amounts of insulin, more extensive structural alterations develop as noted above in conjunction with persistent iris anterior surface and stromal neovascularization. The relationship of rubeosis iridis to clinical inflammatory syndromes and to previous laboratory studies is discussed. Stromal neovascularization was a consistent finding in this experimental model even when anterior surface vessels regressed. On the basis of these experimental data and a review of publications describing human pathology, we believe that a broadening of the classic definition of rubeosis iridis is waranted to include a recognition of the stromal component of the clinical and pathologic findings.

Blau syndrome of granulomatous arthritis, iritis, and skin rash: a new family and review of the literature.

Blau syndrome (MK186580) comprises granulomatous arthritis, iritis, and skin rash, and is an autosomal-dominant trait with variable expressivity. So far it was described in 5 families. We report on a sixth family with severe progression of eye involvement and discuss the nosology with similar diseases, such as early-infantile sarcoidosis.

Laser photocoagulation in the acute retinal necrosis syndrome.

Acute retinal necrosis (ARN) is a syndrome of fulminant necrotizing vaso-occlusive retinitis associated with a high incidence of retinal detachment due to retinal breaks and vitreous traction. We performed argon or krypton laser photo-coagulation to demarcate areas of active retinitis as prophylaxis against retinal detachment in five patients with ARN. Patients were concomitantly treated with antiviral agents, systemic steroids, and antiplatelet therapy. One patient required multiple additional treatments as retinal necrosis progressed. The retinas remained attached in all five patients over a mean follow-up period of 15 months. By creating a chorioretinal adhesion in areas of potential retinal break formation, laser photocoagulation may be an effective prophylaxis against retinal detachment in ARN.

Prophylactic topical cyclosporine in experimental herpetic stromal keratitis.

We determined the anti-inflammatory prophylactic effect of topical cyclosporine in a rabbit model of herpetic stromal keratitis. In a first study, we established that presensitization of rabbits prior to corneal intrastromal injection of herpes simplex virus produced a severe stromal keratitis beginning on day 7 after the intrastromal challenge. Twenty-four presensitized rabbits were thereafter divided into three groups for topical treatment five times a day: (1) 1% cyclosporine in a vehicle solution, started on day 4 after intrastromal challenge, plus 1% trifluridine started on day 7 after challenge, (2) the vehicle solution for cyclosporine, started on day 4, plus 1% trifluridine started on day 7, and (3) the vehicle solution for cyclosporine alone, started on day 4. The severity of stromal disease was significantly decreased in eyes treated with combined cyclosporine-trifluridine, whereas trifluridine alone had no effect on the stromal disease. Epithelial disease did not seem to be worse in eyes treated with combined cyclosporine-trifluridine; the incidence and duration of positive cultures, however, were increased in this group.

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.

Topical nonsteroidal agents and corneal wound healing.

The effects on corneal wound healing of two topical nonsteroidal anti-inflammatory agents, flurbiprofen sodium (0.03%) and diclofenac sodium (0.1%), and the topical corticosteroid, prednisolone sodium phosphate (1%), were evaluated in masked, controlled rabbit studies. Healing of epithelial scrape wounds was significantly retarded in all three treatment groups for the first 3 days after wounding. There was no difference in the epithelial healing rate between the two nonsteroidal or corticosteroid treatment groups. Clinical grading of epithelial quality, conjunctival hyperemia, keratitis, stromal edema, and corneal haze were similar in all groups. There was a significant early decrease in the iritis score in the diclofenac treatment group. The strength of 2-mm central penetrating corneal trephination wounds and the collagen content of these wounds were similar in all groups. Both the topical nonsteroidal anti-inflammatory agents and the corticosteroid used in the preparations and dosages investigated in this study decreased early epithelialization of scrape wounds but had no apparent effect on corneal stromal healing. No toxic effects of the various drugs were found.

Effects of panretinal photocoagulation on rubeosis iridis, angle neovascularization, and neovascular glaucoma.

Ninety-three patients received ruby laser panretinal photocoagulation in one eye for diabetic retinopathy and we examined them at an average time of 7.1 years later. In 14 patients, the untreated eye developed rubeosis iridis and the contralateral treated eye did not. In seven patients, the untreated eye developed angle neovascularization and the contralateral eye did not. The untreated eye developed neovascular glaucoma and the contralateral treated eye did not in four patients. Our findings suggest that eyes with proliferative retinopathy that received panretinal photocoagulation are less likely to develop rubeosis iridis, angle neovascularization, and probably neovascular glaucoma, than those eyes not receiving panretinal photocoagulation.

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.

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.

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.

Histopathological findings in the iris of dapsone treated leprosy patients.

From 43 Nepalese leprosy patients skin smear negative, and treated with dapsone (diamino diphenyl sulphone), and without any sign of active leprosy or iritis, specimens from iridectomy during cataract surgery were studied histopathologically. Of 49 iris specimens only six (12%) were found to be without any histopathological change. Atrophy of the iris stroma was seen in 63% and neovascularisation in 6% of all cases. In 16% in which the dilator muscle could be detected, it was atrophic, and in 11% the pigmented epithelium was thinned and atrophic. Cellular inflammatory infiltrations were seen in 88% of all specimens. They were mostly slight in eyes which before operation had been without posterior synechiae of the iris. In most of the eyes in which posterior synechiae had been present moderate or heavy inflammatory cell infiltrates composed of lymphocytes and plasma cells, often associated with macrophages, neutrophils, or eosinophils, were found. In five iris specimens acid fast bacilli were present. This raises the question whether these can survive systemically despite dapsone chemotherapy in the iris, thus leading to dapsone-resistant leprosy and to recurrent iritis.

Pseudophakic posterior iris chafing syndrome.

Posterior iris chafing by the loop or the optic portion of sulcusfixated posterior chamber lens implants may cause a spectrum of disorders that include iris-pigment epithelial "window defects," pigment dispersion with or without elevation of intraocular pressure, intermittent microhyphemas with transient visual obscurations, and the UGH syndrome. It appears that secondary pigmentary glaucoma is more likely with planar loop design than with angulated loops. Optic and loop materials may play a role in the development of the disorder. Implantation of both supporting loops of the implant within the capsular bag is suggested to prevent posterior iris chafing.

Endothelial line associated with pseudophakic bullous keratopathy.

Three patients undergoing uncomplicated cataract extraction with intraocular lens implantation developed an endothelial line, clinically appearing identical to that seen in allograft rejection following corneal transplantation. Both intracapsular and extracapsular surgery were involved. Three different intraocular lens types were implanted (pupillary supported, anterior chamber, and posterior chamber). Each case was associated with postoperative iritis and glaucoma. They were nonresponsive to steroid therapy and eventually resulted in total corneal decompensation. This clinical entity may represent an autoimmune phenomenon stimulated by chronic inflammation induced by the intraocular lens.