Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used agents that despite chemically heterogeneity, share similar therapeutic properties and adverse effects. Topical ophthalmic NSAIDs are limited to the relatively water soluble phenylacetic and phenylalkanoic acids as well as indole derivatives, which are more suitable for ophthalmic use. Topical ophthalmic NSAIDs are commonly used in the treatment of post-operative inflammation following cataract extraction and various surgical refractive procedures. They are also used in the prevention and treatment of cystoid macular oedema and for the treatment of allergic conjunctivitis. Absorption of topical ophthalmic NSAIDs through the nasal mucosa results in systemic exposure and the occurrence of adverse systemic events, including exacerbation of bronchial asthma. Local irritant effects of topical ophthalmic NSAIDs include conjunctival hyperaemia, burning, stinging and corneal anaesthesia. A more serious complication involves the association of topical ophthalmic NSAIDs with indolent corneal ulceration and full-thickness corneal melts. Analysis of NSAID-associated corneal events implicates the now defunct generic dicolfenac product, diclofenac sodium ophthalmic solution as the agent primarily responsible. However, these events generated a renewed interest in the safety of ophthalmic NSAIDs and a scrutiny of the pharmacology regarding NSAID action in the eye. An elucidation of possible pharmacodynamic explanations of NSAID-induced corneal injury includes the role of epithelial hypoxia, which not only appears to aid in determining the metabolic destination of arachidonate, it may play a key role in orchestrating a novel inflammatory response unrelated to prostanoid formation. The use of NSAIDs under conditions of corneal hypoxia may therefore not only result in a disappointing therapeutic response, it may result in a paradoxical inflammatory exacerbation. Other potential mechanisms include the relationship between NSAIDs and corneal matrix metalloproteinase and direct toxicity due to cytotoxic excipients such as surfactants, solubilisers and preservatives found in topical NSAID ophthalmic preparations. In general, ophthalmic NSAIDs may be used safely with other ophthalmic pharmaceuticals; however, concurrent use of agents known to adversely effect the corneal epithelium, such as gentamicin, may lead to increased corneal penetration of the NSAID. The concurrent use of NSAIDs with topical corticosteorids in the face of significant pre-existing corneal inflammation has been identified as a risk factor in precipitating corneal erosions and melts and should be undertaken with caution. Until clinical evidence dictates otherwise, data supporting theories of potential pharmacodynamic mechanisms of NSAID injury do not alter the favorable benefit-risk ratio of ophthalmic NSAID use when employed in an appropriate and judicious manner.

Accessibility to the bulbar conjunctival microvasculature provides a means to assess blood supply to the cerebral cortex and thus optimize therapeutic interventions designed to prevent or reduce the risk of cerebral vascular disease and stroke. The feasibility of a method for quantitative measurements of conjunctiva blood vessel diameter, blood velocity, and flow in the human eye is reported. The method is based on slit lamp biomicroscope digital imaging coupled with a space time image analysis technique. A sequence of conjunctiva microvasculature images were captured at a rate of 50 Hz. The images were analyzed to determine blood vessel diameter, velocity and flow. Blood vessel diameter measurements ranged between 8.7 and 24.3 microns, with a mean value of 15.5 microns. Blood flow rate ranged between 27.3 and 296.9 pl/s, with a mean value of 111.8 pl/s. The relationship between blood flow and vessel diameter was fit with a power law curve (R = 0.87). The application of this technique for in vivo quantitative assessment of blood flow dynamics has potential to impact diagnosis and monitoring of various cardiovascular and blood disorders.

The removal of diclofenac sodium ophthalmic solution as a viable pharmaceutical entity in September 1999 from the US market spurred considerable interest in the general safety and effectiveness of topical ophthalmic NSAIDs for treatment of anterior segment inflammation. In late 1999 the use of topical ocular NSAIDs declined in the US as a result of incidents involving corneal melts and toxicity surrounding use of generic diclofenac. However, since the removal of diclofenac sodium ophthalmic solution from the marketplace, ophthalmic NSAIDs have regained use as viable pharmacotherapeutic entities. Moreover, several new ophthalmic NSAID products have recently been introduced for commercial use in the US including the novel chemical entity nepafenac. The purpose of this report is to revisit the use of topical ophthalmic NSAIDs for the treatment of surgically induced anterior segment inflammation with a particular focus on nepafenac. Nepafenac is unique among ophthalmic NSAIDs in that it is a prodrug deaminated to amfenac, a highly effective non-selective cyclooxygenase inhibitor. In the case of topical ophthalmic NSAIDs, practitioners should carefully weigh the cost-benefit of implementing “highly potent” new drug products because perturbations in pharmacodynamic response due to the inherent novelty in terms of chemical designs may outweigh the demonstrated replicative pharmacologic action of all topical ophthalmic NSAIDs.

The known biophysical variations of hemoglobin (Hb) S and Hb C may result in hemodynamic differences between subjects with SS and SC disease. The purpose of this study was to measure and compare conjunctival hemodynamics between subjects with Hb SS and SC hemoglobinopathies. Image sequences of the conjunctival microcirculation were acquired in 9 healthy control subjects (Hb AA), 24 subjects with SC disease, and 18 subjects with SS disease, using a prototype imaging system. Diameter (D) and blood velocity (V) measurements were obtained in multiple venules of each subject. Data were categorized according to venule caliber by averaging V and D for venules with diameters less than (vessel size 1) or greater than (vessel size 2) 15 µm. V in vessel size 2 was significantly greater than V in vessel size 1 in the AA and SS groups (P ≥ 0.009), but not in the SC group (P = 0.1). V was significantly lower in the SC group as compared to the SS group (P = 0.03). In AA and SS groups, V correlated with D (P ≥ 0.005), but the correlation was not statistically significant in the SC group (P = 0.08). V was inversely correlated with hematocrit in the SS group for large vessels (P = 0.03); however, no significant correlation was found in the SC group (P ≥ 0.2). Quantitative assessment of conjunctival microvascular hemodynamics in SS and SC disease may advance understanding of sickle cell disease pathophysiology and thereby improve therapeutic interventions.

Purpose To determine alterations in bulbar conjunctival microvascular hemodynamics in sickle cell retinopathy (SCR) subjects with focal macular thinning (FMT). Methods Conjunctival microcirculation imaging and spectral domain optical coherence tomography (SD-OCT) were performed in 22 subjects (eyes) diagnosed with SCR. Based on evaluation of SD-OCT retinal thickness maps, eyes were assigned to one of two groups: with or without FMT. Conjunctival venule diameter and axial blood velocity were measured in multiple venules in each eye by customized image analysis algorithms. Measurements were then categorized into two vessel size groups (vessel size 1 and 2) and compared between FMT groups. A Pearson correlation coefficient was computed to assess the relationship between retinal thickness and axial blood velocity. Results Mean age, hematocrit, sickle cell hemoglobin type, and median retinopathy score were not significantly different between the two groups (p ≥ 0.1). Retinal thickness in parafoveal and perifoveal temporal subfields was significantly lower in eyes with FMT as compared to eyes without FMT (p ≤ 0.04). There was a significant effect of FMT on axial blood velocity (P = 0.04), while the effect of vessel size was not significant (P = 0.4). In vessel size 1, axial blood velocity was lower in eyes with FMT than in eyes without FMT (P = 0.03), while in vessel size 2, there was no statistically significant difference between FMT groups (P = 0.1). In vessel size 1, there was a significant positive correlation between axial blood velocity and retinal thickness in the perifoveal (r = 0.48, P = 0.02) and parafoveal (r = 0.43, P = 0.04) temporal subfields. Conclusion Conjunctival axial blood velocity in small venules is reduced in SCR subjects with focal macular thinning.

Purpose To identify factors associated with best-corrected visual acuity (BCVA) presentation and two-year outcome in 479 intermediate, posterior, and panuveitic eyes. Design Cohort study using randomized controlled trial data Methods Multicenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and 2 years’ follow-up used gold standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and two-year change in BCVA. Results Baseline factors significantly associated with reduced BCVA included: age ≥50 vs. <50 years; posterior vs. intermediate uveitis; uveitis duration >10 vs. <6 years; anterior chamber (AC) flare > grade 0; cataract; macular thickening; and exudative retinal detachment. Over two years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (p=0.52) and 10 letters (p<0.001) respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6–10 or >10 vs. <6 years), incident AC flare, cataract at both baseline and follow-up, pseudophakia at baseline, persistence or incidence of vitreous haze, and incidence of macular thickening. Conclusions Intermediate, posterior and panuveitis have a similarly favorable prognosis with both systemic and fluocinolone acetonide implant treatment. Eyes with more prolonged/severe inflammatory damage and/or inflammatory findings initially or during follow-up have a worse visual acuity prognosis. The results indicate the value of implementing best practices in managing inflammation.

Products that provide a higher number of drops per dollar of product offer economic advantages that may not be otherwise discernible by the examination of the product retail price alone. Furthermore, it is shown that altering the angle of administration may, in general, result in significant economic ramifications in the use of multidose artificial tear products longitudinally.

This study provides evidence that making a supero-oblique clear corneal phacoemulsification incision while sitting in the more natural superior position does not induce a clinically important amount of oblique astigmatism.