Con Petsoglou

Topical Non-Steroidal Anti-Inflammatory Drugs in Allergic Conjunctivitis: Meta-Analysis of Randomized Trial Data

Purpose: To assess the effect of topical Non-Steroidal Anti Inflammatory drugs in the treatment of allergic conjunctivitis. Method: Systematic Review. Data Sources and study selection: Reports of comparative randomized trials of topical NSAIDs and placebo identified by searches of Medline, Embase, the Cochrane Register of Controlled Trials. Data extraction and synthesis: Two reviewers assessed trials for eligibility and quality and extracted data independently. Data were synthesized (random effects model) and results expressed results for dichotomous outcomes as relative risk and continuous outcomes as weighted mean difference. Sensitivity analysis was used to examine potential heterogeneity by differences in study quality. Results: Eight studies incorporating 712 patients were included. The difference between the decrease in allergic sign and symptom score for NSAID treatment compared to placebo was between 4 and 19 percentage points. Topical NSAIDs produced significantly greater relief for conjunctival itching (cardinal symptom) than did placebo (combined standardized mean difference −0.54 (p < 0.001; 95% confidence interval −0.84 to −0.24). The results for the other allergic symptoms: ocular burning/pain, eyelid swelling, photophobia and foreign sensation were not significant. Topical NSAIDs produced significantly greater reduction of conjunctival injection than did placebo (combined standardized mean difference −0.51 (p = 0.03; 95% confidence interval −0.97 to −0.05). Topical NSAIDs did not reduce the allergic signs of conjunctival chemosis, conjunctival mucus, eyelid swelling and corneal disturbance. Topical NSAIDs had a significantly higher rate of burning/stinging on application of medication compared to placebo (P < 0.0001; odds ratio 3.97 (95% CI 2.67 t0 5.89). Conclusion: This meta-analysis confirms that topical NSAID are significantly more effective at relieving the cardinal symptom: conjunctival itching and improving the cardinal sign: conjunctival injection than placebo treatment. A systematic review comparing topical NSAIDs to topical antihistamines/mast cell stabilizers in treatment of allergic conjunctivitis is warranted as this will compare the topical NSAIDs to current therapeutic guidelines.

Immunomodulatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Pro-Inflammatory Cytokine- Stimulated Human Corneal Epithelial Cells

Purpose To investigate the modulatory effect of rat bone marrow mesenchymal stem cells (MSC) on human corneal epithelial cells (HCE-T) stimulated with pro-inflammatory cytokines interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in an in vitro co-cultured model. Methods HCE-T alone and co-cultured with MSC were stimulated with IFN-γ/TNF for 24 and 48 hours or left untreated. The expression of intracellular adhesion molecule (ICAM)-1, human leukocyte antigen ABC, DR and G (HLA-ABC, HLA-DR, HLA-G) were investigated by flow cytometry. Subcellular localization of nuclear factor-kappa B (NF-κB) and expression of indoleamine 2,3-dioxygenase (IDO) were assessed by immunofluorescence staining and western blot. The concentration of transforming growth factor beta 1 (TGF-β1) in the conditioned media from different cultures was evaluated by enzyme-linked immunosorbent assay. NF-κB and TGF-β1 signaling pathway blocking experiments were performed to analyze associations between the expression of cell surface molecules and the NF-κB transcription pathway, and the expression of IDO and TGF-β1 signaling pathway. Results IFN-γ/TNF treatment significantly up-regulated expression of ICAM-1, HLA-ABC, and induced de novo expression of HLA-DR and IDO on HCE-T cultured alone, while HLA-G expression remained unaffected. Up-regulation was significantly inhibited by co-culture with MSC. Increased TGF-β1 secretion was detected in 48 h IFN-γ/TNF-stimulated MSC monocultures and HCE-T/MSC co-cultures. MSC attenuated the activation of cytokine-induced NF-κB and IDO induction. Blockade of NF-κB transcription pathway by BMS-345541 significantly reduced the up-regulation of ICAM-1, HLA-ABC, HLA-DR and IDO expression, while blockade of TGF-β1 signaling pathways reversed the modulatory effect of MSC on IDO expression. Conclusions MSC reduced the expression of adhesion and immunoregulatory molecules on pro-inflammatory cytokine-stimulated HCE-T via the NF-κB transcription pathway. MSC attenuated expression of IDO through both NF-κB transcription and TGF-β1 signaling pathways. Co-culture of HCEC with MSC therefore provides a useful in vitro model to study the anti-inflammatory properties of MSC on corneal epithelium.

Nocardia transvalensis resistant to amikacin: an unusual cause of microbial keratitis.

Purpose: To report a case of microbial keratitis caused by Nocardia transvalensis with resistance to amikacin. Methods: Case report. Results: A 51-year-old man was referred with a 10-week history of ocular pain, photophobia, redness, and blurred vision. At his initial presentation, a corneal foreign body was removed and he was diagnosed with anterior uveitis, with commencement of topical corticosteroid therapy and ofloxacin. Despite treatment, he experienced ongoing foreign body sensation and glare. At presentation to our clinic, a central epithelial defect with multiple stromal infiltrates in a wreath pattern was identified and a diagnosis of infective keratitis was made. He was initially commenced on topical amikacin, oral trimethoprim-sulfamethoxazole, and oral voriconazole. Corneal scraping confirmed Nocardia species. Microbiological culture revealed N. transvalensis as the causative organism, with resistance to several antibiotics, including amikacin. Clinically, there was only partial response of the keratitis to initial therapy. Treatment was changed to oral trimethoprim-sulfamethoxazole and topical ciprofloxacin, with eventual clinical improvement. Conclusions: This is the first reported case of N. transvalensis keratitis. In patients with Nocardia keratitis and only partial response to amikacin treatment, this isolate should be considered as it is resistant to aminoglycoside antibiotics.

Contact lens-related acanthamoeba keratitis.

Acanthamoeba keratitis is a rare but severe disease, with more than 95% of cases occurring in contact lens wearers. With a worldwide resurgence of contact lens-related disease, this report illustrates the clinical characteristics and treatment challenges representative of this disease. This report describes Acanthamoeba keratitis in a 47-year-old female using extended wear silicone hydrogel contact lenses, with a history of swimming in a home pool and failure to subsequently disinfect the contact lenses. The diagnosis was based on clinical signs, disease course, and confocal microscopy results despite a negative result for corneal smear and culture. The corneal signs included an epithelial defect, epithelial irregularities, anterior stromal infiltrates, perineural infiltrates, an anterior stromal ring infiltrate, and hypopyon. The case was diagnosed as an infective keratitis and treated promptly using intensive topical administration of fortified gentamicin and cephalothin. The high likelihood Acanthamoeba prompted immediate use of polyhexamethylbiguanide and chlorhexidine, with propamide and adjunct treatment using atropine and oral diclofenac. Steroids were added on day 3, and the frequency of administration of antibacterial treatment was gradually reduced and ceased by day 10. The analgesia was stopped at 3 months. The frequency of administration of antiamoeba therapy and steroid treatment was slowly reduced and all treatment was ceased after 18 months. Despite considerable morbidity in terms of the treatment duration, hospitalization, outpatient appointments, and associated disease costs, the final visual outcome (6/6) was excellent.

Refractive change in thyroid eye disease (a neglected clinical sign)

Background/aims: The literature on refractive change in thyroid eye disease (TED) is limited. This study documents the refractive change in patients with TED undergoing orbital decompression. The authors propose possible mechanisms for their acquired refractive error. Methods: This is a retrospective observational case study of five patients with progressive TED. Their detailed eye examinations including refractive state preoperatively and postoperatively are presented. Results: An acquired hypermetropic shift with active TED before orbital decompression of up to 3.75D spherical equivalent refraction (SER) is reported in one patient. Post-orbital decompression, an induced myopic shift of between 1.00–2.50D SER for all patients is observed, noted to range from 1 day following surgery to up to 9 months, dependent on the availability of data. Axial length increased in two cases corresponding to postoperative myopic shift. Magnetic resonance imaging findings of one patient demonstrate flattening of the posterior pole as a cause of the acquired preoperative hypermetropia. Conclusions: TED has a significant effect on the refractive state of patients. The proposed mechanism of acquired hypermetropia relates to increased volume of orbital contents with flattening of the posterior globe. This is reversed with successful orbital decompression. Documentation of refractive error in all cases of progressive TED is recommended. Progressive acquired hypermetropia may be suggestive of TED activity.

Repair of isolated abortive cryptophthalmos with lower eyelid switch flap and amniotic membrane graft.

The surgical correction of a case of bilateral isolated abortive cryptophthalmos is described. An upper eyelid and superior fornix were successfully created in a 2-stage procedure using a switch flap from the patients normal lower eyelid and an amniotic membrane graft. Exposure keratopathy was significantly reduced with resultant visual improvement.