A. Exarchou

Matrix metalloproteinases and their inhibitors in exfoliation syndrome

The purpose of this study was to determine the expression of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the aqueous humour of patients with exfoliation syndrome (XFS). XFS and control samples were analysed for their MMP content by zymography and for their tissue inhibitors by ELISA. In XFS eyes, an increase for up to 60% in almost all MMPs was observed, as compared to the controls. MMP-2 and MMP-9 were found to predominate. TIMP-1 levels in XFS samples were slightly decreased, while TIMP-2 levels were similar to those of the controls. Our findings suggest that MMPs may be crucial in the progression of XFS, by degrading the abnormal fibrillar matrix components in the anterior segment tissues of XFS eyes. However, the increased levels of MMPs seem not to be able to overcome the overproduction and accumulation of the exfoliative material.

Angiographically silent cystoid macular oedema secondary to paclitaxel therapy

Bilateral macular oedema is an uncommon side‐effect of paclitaxel administration in oncological patients. We report the case of a 64‐year‐old man who presented with decreased visual acuity due to bilateral macular oedema after paclitaxel administration for lung cancer. Optical coherence tomography scans of both eyes revealed cystoid macular oedema. Fluorescein angiography demonstrated the unusual finding of the absence of localised retinal capillary leakage. Ketorolac eye drops and acetazolamide tablets were prescribed and one month later the cystoid macular oedema resolved with subsequent improvement in visual acuity. This case illustrates the unusual presentation of cystoid macular oedema induced by paclitaxel.

Changes in HNK-1 epitope and collagen type IX in the aqueous humour of patients with pseudoexfoliation syndrome

Purpose. To investigate alterations in the proteoglycan (PG) and glycosaminoglycan (GAG) content of the aqueous humour in patients with pseudoexfoliation syndrome (PEX). Materials and methods. Aqueous humor samples were obtained during cataract surgery from nineteen patients bearing PEX features and twenty-three age-matched normal controls. Protein and IgG were quantified densitometrically after their electrophoretic separation. Collagen type IX, 3-sulphoglucuronic acid (HNK-1 epitope), biglycan and heparan sulphate proteoglycans were detected in Western and dot blots by using specific monoclonal antibodies (MAbs). The immunochemical analysis was performed in native aqueous humour or after degradation of the glycosaminoglycans with chondroitinases. Results. Degradation of the samples with chondroitinases ABC, AC and B revealed that, in the aqueous humour from PEX eyes, collagen type IX and biglycan had a more dermatan sulphate than did normal eyes. In addition, more HNK-1 epitope was observed in PEX eyes, which after similar enzymatic treatment was found to be located mainly in dermatan sulphate sequences. 3-sulphoglucuronic acid was a constituent of the GAG chains of the collagen type IX. We found that the electrophoretic mobility of the bands of collagen type IX and HNK-1 epitope was exactly the same in the aqueous humour of normal and PEX samples; both migrated as four bands at 120, 113, 92.6 and 56 kDa. The PGs bearing heparan sulphate were found only in normal samples. Other PGs were not detected. Conclusion. Because no significant difference was observed in the concentration of albumin and IgG in PEX and normal samples, the blood-aqueous barrier was probably not significantly compromised in PEX patients with cataract but without open-angle glaucoma. The results support the hypothesis that the pathogenesis of PEX can be linked to disturbed metabolism of GAGs and PGs.

Levels of specific antibodies towards the major antigenic determinant of slime-producing Staphylococcus epidermidis determined by an enzyme immunoassay and their protective effect in experimental keratitis.

Staphylococcus epidermidis is an important cause of bacterial keratitis. Certain S. epidermidis strains produce an extracellular slime layer rich in an acidic polysaccharide with a molecular size of 20 kDa (20-kDa PS). We have demonstrated that the level of 20-kDa PS-specific antibodies significantly rises after establishment of slime-producing S. epidermidis bacteraemia and, furthermore, that rabbit polyclonal antibodies to 20-kDa PS opsonize cells of slime-producing S. epidermidis to a great degree and promote their clearance by polymorphonuclear cells (Arch. Biochem. Biophys. 342 (1997) 389; J. Pharm. Biomed. Anal. 22 (2000) 1029). The purpose of this study was to examine the protective and therapeutic effects both of active immunization, using 20-kDa PS as antigen, and of passive administration of specific antibodies towards the 20-kDa PS in a rabbit keratitis model. For active immunization, 20 rabbits were subcutaneously immunized with 20-kDa PS, whereas for passive immunization specific polyclonal IgG antibodies against 20-kDa PS were administered to 20 rabbits 1 day before induction of infection. Clinical observations were made weekly for 1 month and levels of 20-kDa PS antibodies in serum and aqueous humor in both immunization groups were determined by an enzyme immunoassay. The levels of specific anti-20-kDa PS IgG in serum and aqueous humor following either active or passive immunization were significantly higher as compared with control groups (P<0.001). Although, actively immunized rabbits showed significantly less corneal damage than control animals, passively immunized ones were significantly better protected as compared with both control and those actively immunized. Obtained results suggest that 20-kDa PS plays crucial role in the pathogenesis of S. epidermidis keratitis and that both types of immunization significantly protect against corneal S. epidermidis pathology and damage.

Immunization with specific polysaccharide antigen reduces alterations in corneal proteoglycans during experimental slime-producing Staphylococcus epidermidis keratitis

Purpose: Staphylococcus epidermidis is a leading cause of bacterial keratitis associated with corneal damage. Corneal integrity is closely associated with matrix macromolecules, such as proteoglycans (PGs) and collagen. The aim of this study was to examine whether active immunization (AI) using a major immunogenic polysaccharide determinant of slime (20-kDa PS) as antigen, and passive immunization (PI) after administration of specific antibodies toward 20-kDa PS affect the distribution of PGs as well as corneal lesions in an experimental model of slime-producing S. epidermidis keratitis. Methods: For AI, seven rabbits were immunized with 20-kDa PS, whereas for PI, seven rabbits received specific antibodies against 20-kDa PS. Lesions were graded clinically for a 21-day period. Levels of 20-kDa PS antibodies in serum and aqueous humor in both immunization groups were determined by ELISA. The distribution of certain extracellular matrix PGs during corneal healing was analyzed immunohistochemically. Results: Levels of specific anti-20-kDa PS antibodies in serum and aqueous humor obtained after either AI or PI were significantly higher as compared with those in the respective nonimmunized control groups (p < 0.001). Clinical grading showed that both AI and PI rabbits had a significantly less corneal damage as compared with infected nontreated rabbits. Immunohistochemical analyses for PGs exhibited significant differences to the wounded regions as compared with noninfected corneal tissue. Accumulation of keratan sulfate PGs and decorin was observed in the corneal stroma of infected rabbits and of heparan sulfate PGs around the new-formed vessels. This phenomenon was significantly reduced in immunized animals in accordance with macroscopically decreased corneal damage observed in these animals. Conclusions: Results of this study suggest a key role of 20-kDa PS and its antibodies as prophylactic and therapeutic agents in keratitis caused by slime-producing S. epidermidis.

Alterations in conjunctival cytology and tear film dysfunction in patients with beta-thalassemia.

Purpose Patients with &bgr;-thalassemia (&bgr;-tha) represent a group with lifelong transfusion-dependent anemias. This study aimed to describe the conjunctival changes and tear film parameters in these patients. Methods A total of 52 patients (104 eyes) with &bgr;-tha major and 22 normal control subjects (44 eyes) were studied during 1999 through 2000. Tear film break-up time (BUT), Schirmer test, rose Bengal staining, and cytologic evaluation of the conjunctival epithelium were performed in all subjects. The Papanicolaou and May-Grümwald-Giemsa staining procedures were performed on all smears. Patients and control subjects were compared for tear function parameters and conjunctival changes. Results The BUT, Schirmer test, and rose Bengal staining values were significantly lower (P < 0.001) in &bgr;-tha patients than in control subjects. Keratinized cells were observed in conjunctival samples in 41% of patients, with a decrease in the number of goblet cells per slide in 64% of patients. In 9% of &bgr;-tha patients, there were a slightly greater number of inflammatory cells than in control eyes. Conclusion Ocular surface disorder of these patients was characterized by goblet cell loss and conjunctival squamous metaplasia. Our findings were correlated positively with the variable age. Epithelial damage by toxic reaction and disorder of tear quality and quantity are implicated as important factors in the pathogenesis of the ocular surface disease in &bgr;-tha patients.

Unusual case of acanthamoeba keratitis in a contact lens wearer.

Purpose. To present an atypical case of acanthamoeba keratitis in a soft contact lens wearer. Methods. A case report of a 28-year-old female soft contact lens wearer with a 6-day history of redness and blurred vision in her right eye. Examination showed stromal keratitis that did not respond to therapy for herpes simplex virus. Four weeks later, the patient had increased stromal infiltration, an endothelial plaque, and a hypopyon. She did not complain of pain apart from mild discomfort. Corneal smears and anterior chamber tap were negative for bacteria, fungi, acanthamoeba, and herpes simplex virus, and the patient was prescribed fortified antibiotics. One week later, a large epithelial defect with a surrounding ring infiltrate was apparent. Corneal biopsy showed acanthamoeba. Results. The acanthamoeba keratitis resolved with successful treatment. One year later, the patient had a residual visual deficit secondary to stromal scarring and her best-corrected visual acuity was 20/29. Conclusions. This case emphasizes the importance of considering acanthamoeba species in the differential diagnosis of keratitis, even without the classic symptom of severe pain. A high degree of suspicion with rapid and appropriate treatment may result in improved recovery of vision.

Diplopia due to systemic lupus erythematosus in a child: a rare clinical presenting sign of the disease.

We present the case of a 14-year-old girl who was admitted to the hospital with the complaint of horizontal diplopia for 48 hours. Initially, she was diagnosed with idiopathic intracranial hypertension. During hospitalization she developed fever, macular facial rash, and chest pain, and because of abnormal laboratory findings the diagnosis of systemic lupus erythematosus was established. She received immunomodulatory therapy, a combination of corticosteroids, and intravenous infusions of the monoclonal antibody rituximab, which augmented her clinical improvement. Intracranial hypertension secondary to systemic lupus erythematosus is a rare manifestation, especially as a presenting symptom. In addition, the fact that the patient developed an aggressive form of systemic lupus erythematosus during the initial period of hospitalization for idiopathic intracranial hypertension is also uncommon. Moreover, to our knowledge, we are not aware of any published case reports of intracranial hypertension secondary to systemic lupus erythematosus that was treated with rituximab.

Intravitreal Ranibizumab as Palliative Therapy for Iris Metastasis Complicated With Refractory Secondary Glaucoma.

Purpose:To report a case where iris metastasis was the presenting sign of hitherto undiagnosed non–small cell lung carcinoma. The diagnostic approach and patient management are discussed. Methods:A 51-year-old man presented with pain due to an iris mass and neovascular glaucoma. Results:Systemic evaluation subsequently led to the diagnosis of non–small cell lung carcinoma and the iris mass was considered metastatic. The patient refused any systemic therapy and accepted only intervention for ocular pain relief. Ranibizumab was administered intravitreally and resulted in subsidence of iris mass and new vessels and pain relief, which enhanced the patient’s quality of life. Conclusions:This is the first known report where intravitreal injection of ranibizumab was used as palliative treatment for refractory neovascular glaucoma due to iris metastasis.

Atypical Cogan's syndrome presenting as bilateral endogenous endophthalmitis

We report a case of atypical Cogans syndrome presenting as bilateral endogenous endophthalmitis in a woman with ovarian cancer. A 62‐year‐old woman with ovarian cancer developed bilateral interstitial keratitis and panuveitis accompanied by bilateral sensorineural hearing loss and chondritis. Auricular cartilage biopsy ruled out relapsing polychondritis and the diagnosis of atypical Cogans syndrome was set clinically.