Salman Sarwar

Endogenous endophthalmitis: diagnosis, management, and prognosis

Endogenous endophthalmitis is an ophthalmic emergency that can have severe sight-threatening complications. It is often a diagnostic challenge because it can manifest at any age and is associated with a number of underlying predisposing factors. Microorganisms associated with this condition vary along a broad spectrum. Depending upon the severity of the disease, both medical and surgical interventions may be employed. Due to rarity of the disease, there are no guidelines in literature for optimal management of these patients. In this review, treatment guidelines based on clinical data and microorganism profile have been proposed.

What have we learnt about the management of diabetic macular edema in the antivascular endothelial growth factor and corticosteroid era

Purpose of review To summarize the outcomes of the use of antivascular endothelial growth factor (anti-VEGF) agents and corticosteroids on the treatment paradigm for diabetic macular edema (DME). Recent findings Favorable efficacy data along with acceptable long-term safety results of anti-VEGF agents have made them the standard first-line therapy in the management of DME. Level I evidence from large, multicenter clinical trials has established the beneficial role of anti-VEGF agents and intravitreal steroids. In addition, the role of anti-VEGF agents in the treatment of diabetic retinopathy has also been recently recognized. However, concerns such as suboptimal response, VEGF resistance, and long-term effects on retinal layers and vasculature have also been highlighted recently. Summary The use of anti-VEGF agents and corticosteroids has revolutionized the management of DME. Despite the advantages including ease of administration, low incidence of adverse events, and concomitant improvement in retinopathy status, limitations of this therapeutic approach have been recognized. The current review will focus on the lessons learnt in the management of DME in the anti-VEGF and steroid era.

Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

Contemporary management of neovascular age-related macular degeneration (AMD) has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described.

Platelet derived growth factor inhibitors: A potential therapeutic approach for ocular neovascularization

Retinochoroidal vascular diseases are the leading causes of blindness in the developed world. They include diabetic retinopathy (DR), retinal vein occlusion, retinopathy of prematurity, age-related macular degeneration (AMD), and pathological myopia, among many others. Several different therapies are currently under consideration for the aforementioned disorders. In the following section, agents targeting platelet-derived growth factor (PDGF) are discussed as a potential therapeutic option for retinochoroidal vascular diseases. PDGF plays an important role in the angiogenesis cascade that is activated in retinochoroidal vascular diseases. The mechanism of action, side effects, efficacy, and the potential synergistic role of these agents in combination with other treatment options is discussed. The future of treatment of retinochoroidal vascular diseases, particularly AMD, has become more exciting due to agents such as PDGF antagonists.

Platelet-Derived Growth Factor Inhibitors: A Potential Therapeutic Approach for Ocular Neovascularization

Retinochoroidal vascular diseases are the leading causes of blindness in the developed world. They include diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, age-related macular degeneration (AMD), and pathological myopia, among many others. Several different therapies are currently under consideration for the aforementioned disorders. In the following section, agents targeting platelet-derived growth factors (PDGF) are discussed as a potential therapeutic option for retinochoroidal vascular diseases. PDGF play an important role in the angiogenesis cascade that is activated in retinochoroidal vascular diseases. The mechanism of action, side effects, efficacy, and the potential synergistic role of these agents in combination with other treatment options is discussed. The future of treatment of retinochoroidal vascular diseases, particularly neovascular AMD, has become more exciting due to agents like PDGF antagonists.

High-Resolution Imaging of Parafoveal Cones in Different Stages of Diabetic Retinopathy Using Adaptive Optics Fundus Camera

Purpose To assess cone density as a marker of early signs of retinopathy in patients with type II diabetes mellitus. Methods An adaptive optics (AO) retinal camera (rtx1™; Imagine Eyes, Orsay, France) was used to acquire images of parafoveal cones from patients with type II diabetes mellitus with or without retinopathy and from healthy controls with no known systemic or ocular disease. Cone mosaic was captured at 0° and 2°eccentricities along the horizontal and vertical meridians. The density of the parafoveal cones was calculated within 100×100-μm squares located at 500-μm from the foveal center along the orthogonal meridians. Manual corrections of the automated counting were then performed by 2 masked graders. Cone density measurements were evaluated with ANOVA that consisted of one between-subjects factor, stage of retinopathy and the within-subject factors. The ANOVA model included a complex covariance structure to account for correlations between the levels of the within-subject factors. Results Ten healthy participants (20 eyes) and 25 patients (29 eyes) with type II diabetes mellitus were recruited in the study. The mean (± standard deviation [SD]) age of the healthy participants (Control group), patients with diabetes without retinopathy (No DR group), and patients with diabetic retinopathy (DR group) was 55 ± 8, 53 ± 8, and 52 ± 9 years, respectively. The cone density was significantly lower in the moderate nonproliferative diabetic retinopathy (NPDR) and severe NPDR/proliferative DR groups compared to the Control, No DR, and mild NPDR groups (P < 0.05). No correlation was found between cone density and the level of hemoglobin A1c (HbA1c) or the duration of diabetes. Conclusions The extent of photoreceptor loss on AO imaging may correlate positively with severity of DR in patients with type II diabetes mellitus. Photoreceptor loss may be more pronounced among patients with advanced stages of DR due to higher risk of macular edema and its sequelae.

Adaptive Optics Imaging of Retinal Photoreceptors Overlying Lesions in White Dot Syndrome and its Functional Correlation.

PURPOSE To quantify retinal photoreceptor density using adaptive optics (AO) imaging and correlate it with retinal tomography, fundus autofluorescence, and retinal sensitivity overlying lesions in various white dot syndromes (WDS). DESIGN Prospective cross-sectional study. METHODS setting: Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA. STUDY POPULATION Thirty-five lesions of WDS from 12 patients (19 eyes; mean age: 54.4 ± 15.8 years; 9 female) were analyzed. INTERVENTION Macular lesions (≤3 regions of interest/eye), at 2 fixed eccentric loci, were imaged using AO, spectral-domain optical coherence tomography, and fundus autofluorescence. In this study, lesions were defined as active if there was presence of hyperautofluorescence within the lesions. Photoreceptor density was calculated after manual correction and adjustment for axial length. Retinal sensitivity was assessed using microperimetry and correlated with photoreceptor density using Spearman rank correlation test. OUTCOME MEASURES Mean retinal sensitivity and photoreceptor density at the WDS lesions. RESULTS Mean photoreceptor density was 7331 ± 4628 cones/mm(2) overlying 16 active lesions and 6546 ± 3775 cones/mm(2) overlying 19 inactive lesions (P = .896). Mean retinal sensitivity (9.37 ± 5.34 dB) showed modest correlation with photoreceptor density (ρ = 0.42, P = .03). Retinal sensitivity over lesions with intact inner segment-outer segment (IS-OS) junction was 13.35 ± 3.75 dB and 6.33 ± 4.31 dB over lesions with disrupted IS-OS junction (P = .005). CONCLUSIONS AO imaging may allow high-resolution analysis of photoreceptor loss among lesions in WDS. Such microstructural changes may correlate with functional loss.

Sustained-release fluocinolone acetonide intravitreal insert for macular edema: clinical pharmacology and safety evaluation

Introduction: Inflammation plays a key role in the pathological processes leading to macular edema. Sustained release, low-dose intraocular corticosteroid delivery devices provide long-term anti-inflammatory therapy. Recently, a novel fluocinolone acetonide intravitreal insert (FAi, Iluvien), has been introduced with promising long-term results in the treatment of macular edema. Areas covered: An extensive review of the literature in the English language was performed to provide comprehensive information on the pharmacological properties of FAi and its safety and efficacy data from various multi-center randomized clinical trials. Expert opinion: The FAc, Retisert is a sustained-release device that is surgically implanted in the vitreous and has been approved by the US FDA for the treatment of non-infectious intermediate, posterior or panuveitis. FAi was developed after FAc and is an intravitreal corticosteroid delivery system that allows controlled release of therapeutic levels of fluocinolone acetonide (FA). Initial efficacy and safety data suggest that this delivery system maintains clinical effectiveness for up to 3 years after a single delivery of the device. This second-generation fluocinolone delivery device has shown superior safety results in clinical trials compared to the previous version of the higher dose FAc (0.59 mg). Sustained delivery preparations may help to reduce the treatment burden and its associated risks by decreasing the frequency of intravitreal injections. However, much needs to be learnt from additional clinical trials, post-marketing surveillance and results of extension studies. Concerns of intravitreal corticosteroids, such as cataract and increase in intraocular pressure, remain major challenges for this therapeutic strategy.

Fusion Proteins: Aflibercept (VEGF Trap-Eye)

Vascular endothelial growth factor (VEGF) inhibitors currently used to treat eye diseases have included monoclonal antibodies, antibody fragments, and an aptamer. A different method of achieving VEGF blockade in retinal diseases includes the concept of a cytokine trap. Cytokine traps are being evaluated for the treatment of various diseases that are driven by excessive cytokine levels. Traps, such as VEGF Trap, consist of two extracellular cytokine receptor domains fused together to form a human IgG. Aflibercept (VEGF Trap-Eye) is a soluble fusion protein which combines ligand-binding elements taken from the extracellular components of VEGF receptor (VEGFR)-1 and VEGFR-2 fused to the Fc portion of IgG. This protein contains all human amino-acid sequences, which minimizes the potential for immunogenicity in human patients. The chapter will summarize the chemical properties of aflibercept and the various studies that have demonstrated a role of aflibercept in the management of retinal vascular diseases such as neovascular age-related macular degeneration, diabetic retinopathy, macular edema, and retinal vein occlusion.

SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY EVALUATION OF RETINAL STRUCTURE IN PATIENTS WITH SUSACS SYNDROME.

Purpose: To report spectral-domain optical coherence tomography (SD-OCT) features in patients diagnosed with Susacs syndrome. Methods: Clinical report of two cases. Results: Spectral-domain optical coherence tomography was performed in two patients diagnosed with Susacs syndrome. Both the patients had normal macular perfusion on fluorescein angiography (FA). However, SD-OCT revealed bilateral, temporal macular atrophy with disorganization and thinning of the retinal layers. The outer plexiform layer showed nodularity and waviness suggestive of ischemic swelling of the bipolar cells. Conclusion: Retinal structural changes in Susacs syndrome have not been described earlier. Spectral-domain optical coherence tomography may be more sensitive than fluorescein angiography in detecting microstructural retinal alterations in various layers, especially in apparently perfused retina. These findings may provide an insight into the pathogenesis of Susacs syndrome.