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PurposeTo assess the impact on visual acuity of delays between diagnosis and treatment in patients with subfoveal neovascular age-related macular degeneration (NV-AMD) and to evaluate NV-AMD patients' emotional status before therapy initiation.MethodsThis retrospective, multicenter, epidemiological study included newly diagnosed NV-AMD patients registered in the Spanish national health system and referred to regional health centers for evaluation/treatment by a retinal specialist from 09/2005 to 03/2006. Records were reviewed and data abstracted at referring physicians' offices (diagnosis visit) and regional health centers (treatment visit). Treatment was at physicians' discretion. The Hospital Anxiety and Depression Scale was administered at the treatment visit (before therapy).ResultsMedian time from the diagnosis to treatment visit was 2.3 months (95% confidence interval: 0.2–10.8 months). Vision loss had progressed at the treatment visit with a doubling in the percentage of patients with a visual acuity of 20/400 or worse (from 12.4 to 24.7%). The decrease in visual acuity from the diagnosis to the treatment visit was highly statistically significant (P<0.0001) as was the correlation between months to treatment and visual acuity change (r=0.5234, P<0.0001). Time from the diagnosis to the treatment visit remained a significant predictor of progressive vision loss when visual acuity at diagnosis and change in lesion size between diagnosis and treatment were controlled (P<0.0001). Patients with more severe vision loss prior to treatment tended to report more depression.ConclusionsDelayed treatment of patients newly diagnosed with NV-AMD is associated with substantial visual acuity loss.Eye (2009) 23, 326–333; doi:10.1038/sj.eye.6703053; published online 18 January 2008 [ABSTRACT FROM AUTHOR]

Background/aims: Pregnancy and the postpartum period are associated with the activity of autoimmune diseases including uveitis. Although the exact mechanism is unknown, hormones are reported to alter inflammatory cytokines and influence disease activity. The authors studied ocular inflammation, female hormones, and serum cytokine levels during and alter pregnancy. Methods: A prospective, observational case study was conducted. Four pregnant women in their first trimester with chronic nominfeclious uveitis were followed monthly until: 6 months after delivery. Serum female hormones (oestrogen, progesterone, prolactin) and various cytokines (1L-2, 1L-4, 1L- 5, IL-6, 1L-10, IFN-&#x03B3, and TGF-β) were measured by ELISA. Results: The four patients had live lull term pregnancies. Uveitis activity decreased after the first trimester but flared in the early postpartum period. Serum female hormones, highly elevated during pregnancy, drastically dropped post partum. Cytokine levels except TGF-β were mostly undetectable. Conclusion: Female hormones and TGF-β may contribute to the activity of uveitis during pregnancy and the postpartum period. [ABSTRACT FROM AUTHOR]

Purpose: The kinetics of various cytokines in the eye plays a critical role in endotoxin-induced uveitis (EIU). This study examined the cytokine kinetics and susceptibility of EIU in four mice strains.Methods: Four strains of TLR-4 or Toll-like receptor-4 (Lps, lipopolysaccharide-susceptible) gene-positive mice (C3H/HeN of H-2(k), C57/B6 of H-2(b), Balb/C of H-2(d), and 129/J of H-2(b)) were injected subcutaneously with either lipopolysaccharide (LPS) in phosphate-buffered saline (PBS) or PBS alone in two repeated experiments. Mice were sacrificed 1, 3, 6, 24 (1 d), 72 (3 d), 120 (5 d), or 168 (7 d) hours after LPS injection. Ocular histology and reverse transcriptase-polymerase chain reaction (RT-PCR) to detect ocular interleukin-1 alpha (IL-1 alpha), IL-6, tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA were performed. Serum IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha levels were measured using enzyme-linked immunosorbent assay (ELISA).Results: No ocular inflammation was present in any mice within six hours after LPS injection. Only the C3H/HeN mice developed a biphasic ocular inflammatory response (1 d and 5 d), during which all proinflammatory cytokine messages were expressed. In the other three strains with minimal (129/J and Balb/C) to mild (C57/B6) EIU that peaked at 1 d, IL-6 mRNA was barely detectable in C57/B6 and Balb/C; GM-CSF mRNA was also present in C57/B6. Serum IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were high in all EIU mice within six hours after LPS injection. Control mice did not develop uveitis or measurable cytokine messages.Conclusion: In the most susceptible strain, C3H/HeN, EIU was biphasic and correlated to multiple proinflammatory cytokines released in the eye. The less susceptible mice strains exhibited a monophasic response to LPS that may result from no cytokine cascade. [ABSTRACT FROM AUTHOR]

Purpose The relationship between ocular surface inflammation, signs and symptoms in DED remains poorly understood. A correlation between ocular surface inflammation and CFS in DED patients is reported. Methods DED patients with tear break up time ≤8 seconds and CFS grades 2‐4 modified Oxford scale and Schirmer test without anesthesia ≥2 and <10 mm/5min and lissamine green staining, Van Bijsterveld >4 and at least 1 dry eye symptom were randomized to CYCLOKAT® (unpreserved 0.1% cyclosporine cationic emulsion) or vehicle QD. Impression cytology for conjunctival HLA‐DR expression (an ocular surface inflammatory biomarker) was performed in a subset of patients. Results Cytology samples were collected in 89 of 492 patients. At baseline the mean HLA‐DR expression was higher in the CYCLOKAT® (84,345 AUF vs 46,888 AUF) arm. Notably, the mean HLA‐DR expression increased with baseline CFS grade (grade 2: 48,343; grade 3: 56,749; grade 4: 127,623). At month 6, CYCLOKAT® significantly reduced the HLA‐DR expression (‐50896 AUF vs ‐1192 AUF, p=0.022). The efficacy of CYCLOKAT® on improving CFS [as measured by mean change (delta of CYCLOKAT® over vehicle) and % achieving ≥ 2 grade improvement] increased with the CFS grade at baseline (grade 2‐4: 0.22 and 33.6% vs 21.8%, grades 3‐4: 0.32 and 40.4% vs 27.7%, grade 4: 0.77 and 48.8% vs 19.5%, p<0.05 for all comparisons). Conclusion The demonstrated correlation between HLA‐DR expression and CFS support the role of inflammation in DED and justifies the need for anti‐inflammatory therapy. The benefit of CYCLOKAT® appears to be greatest in patients with severe DED. Commercial interest [ABSTRACT FROM AUTHOR]

Purpose Resolution of papillae is a desirable objective in the management of tarsal VKC. The effect of Vekacia®, an unpreserved cyclosporine cationic emulsion, was evaluated in children with active VKC presenting with giant papillae and keratitis at enrollment. Methods 118 VKC patients were randomized to Vekacia® 0.05%, 0.1%, or vehicle QID. The primary criterion was subjective symptom improvement. Objective signs (giant papillae, conjunctival hyperemia, discharge, chemosis, limbal infiltrates and corneal epithelial disease) were assessed as secondary endpoint. Results At Day 28, patient subjective symptoms improved in all groups without statistically significant difference between groups. Among the objective signs, except for papillae, clinically significant improvements were observed: absence of the sign ranged from 20.5% to 72% in both active groups and from 16.7% to 41.2% for vehicle group, depending of the sign. For papillae, only 4 patients experienced total clearing (2.8%, 2.6% and 6.6% in vehicle, 0.05% and 0.1% CsA groups respectively). Clinically and statistically significant differences in keratitis (CFS mean change) over vehicle were observed at Day 28 in Vekacia® treated patients (0.05%, p=0.003; 0.1% p=0.014). Conclusion Corneal involvement in VKC is a sight‐threatening complication. Improvement in keratitis, a key element in the management of the active VKC was not associated with complete resolution of the papillae. Therefore, among the signs of the disease, papillae appear to be the least helpful sign to follow VKC improvement. Commercial interest [ABSTRACT FROM AUTHOR]

Purpose Ocular surface damage is a consequence of tear instability arising from numerous inciting events: preserved eye drops, contact lens wear, systemic medications, environment and age. While unpreserved eye drop reduce iatrogenic toxicity they do not restore the deficient tear film which leads to ocular surface injury. Cationic oil‐in‐water emulsions have been shown to restore and reduce evaporation of the tear film. We studied the effect of cationic emulsions (Cationorm® and Catioprost®) in established animal models of ocular surface injury. Methods Acute toxicity and local tolerance were evaluated in rabbits. Healing properties were assessed in a rat model of corneal scraping. Abrasions were treated for 5 days, and corneas were evaluated clinically and histologically. Conjunctival function was assessed by goblet cell (GC) count and MUC5 immunostaining. The kinetics of ocular surface healing was assessed in an in vitro scraping assay. Results Neither Cationorm® nor Catioprost® induced toxicity as evidenced by clinical and confocal microscopy scoring. Catioprost® was well tolerated, with a reduced (‐42%) occurrence of hyperemia when compared to Xalatan®. In rats, Catioprost® improved healing, protected GC and maintained normal MUC5 secretion. In vitro, the cationic emulsions improved cell migration and maintained MUC4 expression. Conclusion Cationic emulsions were well tolerated. In contrast to preserved and unpreserved ophthalmic drops, cationic emulsions promoted healing, restored function of injured ocular surface, and protected against ocular surface injury. The findings suggest that cationic emulsions by augmenting the tear film may benefit patients with ocular surface disease. Commercial interest [ABSTRACT FROM AUTHOR]

Purpose Ocular Surface Disease (OSD), recognized in 50% of glaucoma patients, can decrease anti‐glaucoma therapy compliance. Benzalkonium chloride (BAK) has been shown to induce OSD. Catioprost® is an unpreserved latanoprost 0.005% cationic emulsion. The design of a study comparing the efficacy and safety of Catioprost® versus a BAK‐free prostaglandin agonist, Travatan Z® (travoprost 0.004%) in patients with glaucoma and OSD is described. Methods Patients with elevated IOP at baseline requiring treatment with ocular anti‐hypertensive therapy were enrolled in this multicenter, phase II, investigator‐masked, randomized study. Following a washout period, patients demonstrating OSD symptoms and signs (corneal fluorescein staining, CFS, score≥1 on the modified Oxford scale and a tear film break up time, TFBUT, ≤10) in at least one eye at the baseline visit were randomized to either Catioprost® or Travatan Z® QD with follow‐up study evaluations at month 1 and 3. Results 105 patients were randomized. Change in diurnal IOP, a change in the global symptoms (ocular discomfort, burning, dryness, grittiness, stinging) and objective signs (CFS, TFBUT, conjunctival hyperemia) of OSD at month 1 and 3 will be presented. Safety outcomes will also be reported. Conclusion Preservative free prostaglandin agonists reduce the risk of ocular toxicity associated with BAK. However, their effect on restoring ocular surface damage is unclear. In this study, the efficacy and safety of an unpreserved latanoprost 0.005% cationic emulsion relative to BAK‐free travoprost 0.004% solution on reducing IOP and improving the signs and symptoms of OSD will be revealed. Commercial interest [ABSTRACT FROM AUTHOR]