Interferon-α-induced retinopathy in chronic hepatitis C treatment: summary, considerations, and recommendations.

Interferons are cytokines that regulate the host's response to viral infection, particularly in the setting of the immunologic response to the hepatitis C virus (HCV). While the virus has the ability to evade the host's innate and specific immunity, exogenous interferon-α with combined ribavirin, treatments have been found to achieve a significant sustained viral response in subgroups of patients with chronic HCV. One of the major side effects of interferon-α is an ocular retinopathy characterized by flame-shaped hemorrhages and cotton wool spots visualized on funduscopic examination. There have been documented cases of more severe side effects including optic nerve and retinal artery damage; however, these instances are the minority. We sought to investigate the literature surrounding interferon-induced retinopathy, clinically correlate our findings with two recent cases, and provide recommendations for practitioners who continue to manage chronic HCV patients using interferon-α with combined ribavirin treatments.

Effect of Vitreomacular Adhesion on Treatment Outcomes in the Ranibizumab for Edema of the Macula in Diabetes (READ-3) Study.

PURPOSE: To assess the role of vitreomacular adhesion (VMA) in visual and anatomic outcomes in patients with diabetic macular edema (DME). DESIGN: Retrospective cohort study. PARTICIPANTS: Data from patients enrolled in the Ranibizumab for Edema of the Macula in Diabetes: Protocol 3 with High Dose (READ-3) study were analyzed. METHODS: In the READ-3 study, patients with DME received monthly intravitreal injections of either 0.5 or 2.0 mg ranibizumab. Optical coherence tomography images from patients who completed the month 6 visit of the study were analyzed at the baseline visit to identify the presence (VMA+) or absence (VMA-) of VMA. Patients with any degree of vitreomacular traction were excluded from the analysis. Two independent graders graded all images. Vitreomacular adhesion was classified by size of adhesion into either focal (<1500 µm) or broad (≥1500 µm). MAIN OUTCOME MEASURES: Mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at month 6 and incidence of posterior vitreous detachment (PVD). RESULTS: One hundred fifty-two eyes (152 patients) were randomized in the READ-3 study. One hundred twenty-four eyes (124 patients) were eligible for the study based on study criteria. Twenty-eight eyes did not meet study criteria and were excluded from the study. At baseline, 26 patients were classified as VMA+ and 98 patients were classified as VMA-. The distribution of the 2 doses of ranibizumab (0.5 and 2.0 mg) in the 2 groups was similar. At month 6, the mean improvement in BCVA was 11.31±6.67 and 6.86±7.58 letters in the VMA+ and VMA- groups, respectively (P = 0.007). Mean improvement in CRT was -173.81±132.31 and -161.84±131.34 µm in the VMA+ and VMA- groups, respectively (P = 0.681). At month 6, among the 26 VMA+ eyes (at baseline), 7 eyes demonstrated PVD, 17 eyes showed no change in VMA status, and 2 eyes were not gradable and were excluded. CONCLUSIONS: Diabetic macular edema patients with VMA have a greater potential for improvement in visual outcomes with anti-vascular endothelial growth factor therapy. Therefore, the presence of VMA should not preclude patients with DME from receiving treatment.

Aflibercept for neovascular age-related macular degeneration.

BACKGROUND: Central vision loss caused by age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Neovascular AMD is characterized by choroidal neovascularization (CNV). Growth of new blood vessels in patients with neovascular AMD is driven by a complex process that involves a signal protein called vascular endothelial growth factor A (VEGF-A). Anti-VEGF drugs that block this protein include ranibizumab, bevacizumab, and aflibercept. OBJECTIVES: To assess and compare the effectiveness and safety of intravitreal injections of aflibercept versus ranibizumab, bevacizumab, or sham for treatment of patients with neovascular AMD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (Issue 11, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched December 4, 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on November 30, 2015. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which aflibercept monotherapy was compared with ranibizumab, bevacizumab, or sham for participants with neovascular AMD who were treatment-naive. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures of The Cochrane Collaboration for screening, data abstraction, and study assessment. Two review authors independently screened records, abstracted data, and assessed risk of bias of included studies; we resolved discrepancies by discussion or with the help of a third review author when needed. MAIN RESULTS: We included two RCTs (total of 2457 participants, 2457 eyes). Trial participants had neovascular AMD with active subfoveal choroidal neovascular lesions. Both trials followed the same protocol and compared aflibercept at various doses versus ranibizumab, but they were carried out in different countries. One trial enrolled participants from the United States and Canada, and the second trial was conducted at 172 sites in Europe, Asia Pacific, Latin America, and the Middle East. The overall quality of the evidence was high, and included trials were at low risk for most bias domains assessed; however, both trials were funded by the manufacturers of aflibercept. For the purposes of analysis, we combined aflibercept groups regardless of dosing and analyzed them as a single group.Visual acuity outcomes were similar between aflibercept and ranibizumab groups; at one year, participants in the aflibercept groups showed mean change in best-corrected visual acuity (BCVA) from baseline similar to that of participants in the ranibizumab groups (mean difference (MD) -0.15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% confidence interval (95% CI) -1.47 to 1.17; high-quality evidence). At two years, the mean change in BCVA from baseline was 7.2 ETDRS letters for aflibercept groups versus 7.9 for ranibizumab groups. Sufficient data were not available for calculation of confidence intervals.The proportion of participants who gained 15 or more letters of BCVA by one year of follow-up was approximately 32% for both aflibercept and ranibizumab (RR 0.97, 95% CI 0.85 to 1.11; high-quality evidence), and by two years of follow-up was approximately 31% (RR 0.98, 95% CI 0.85 to 1.12; high-quality evidence). Similar small proportions of participants in the aflibercept and ranibizumab groups lost 15 or more letters of BCVA at one year (RR 0.89, 95% CI 0.61 to 1.30; high-quality evidence); this outcome was not reported for two-year follow-up. Data were not reported on the proportion of participants with BCVA worse than 20/200 at one- or two-year follow-up.Participants treated with aflibercept or ranibizumab showed similar improvement in morphological outcomes, as assessed from images (central retinal thickness and CNV size). At one year, the proportion of eyes that achieved dry retina was similar between aflibercept and ranibizumab groups (absence of cystic intraretinal fluid and subretinal fluid on optical coherence tomography (OCT); RR 1.06, 95% CI 0.98 to 1.14; high-quality evidence). In addition, investigators reported no difference in reduction of CNV area between aflibercept- and ranibizumab-treated eyes at one year (MD -0.24 mm(2), 95% CI -0.78 to 0.29; high-quality evidence). Data were not reported for the proportion of eyes with absence of leakage on fluorescein angiography at one- or two-year follow-up.Overall, occurrence of serious systemic adverse events was similar and comparable in aflibercept- and ranibizumab-treated groups at one year (RR 0.99, 95% CI 0.79 to 1.25). Risk of any serious ocular adverse event was lower in the aflibercept group than in the ranibizumab group, but the risk estimate is imprecise (RR 0.62, 95% CI 0.36 to 1.07). As the result of imprecision, we graded the quality of evidence for all adverse events as moderate. AUTHORS' CONCLUSIONS: Results of this review document the comparative effectiveness of aflibercept versus ranibizumab for visual acuity and morphological outcomes in eyes with neovascular AMD. Current available information on adverse effects of each medication suggests that the safety profile of aflibercept is comparable with that of ranibizumab; however, the number of participants who experienced adverse events was small, leading to imprecise estimates of absolute and relative effect sizes. The eight-week dosing regimen of aflibercept represents reduced treatment requirements in comparison with monthly dosing regimens and thus has the potential to reduce treatment burden and risks associated with frequent injections.

Introduction to microperimetry and its use in analysis of geographic atrophy in age-related macular degeneration.

PURPOSE OF REVIEW: This article discusses recent advances in the fundus-guided perimetry (microperimetry) and its utilization in evaluation and monitoring of patients with geographic atrophy. RECENT FINDINGS: Although best-corrected visual acuity has been gold standard in clinical practice for decades, it does not provide an entire assessment of visual function that determines daily activity and quality of life of a patient. Furthermore, psychophysical tests, including low-luminance visual acuity, reading speed, and contrast sensitivity, cannot be used to quantify retinal sensitivity or detect pattern of retinal dysfunction. Microperimetry provides a true evaluation of visual function by offering fundus-controlled testing through eye-tracking technology that allows for structural and functional correlation and test-retest reliability for the same test point. Furthermore, it enables precise assessment of location and stability of fixation. Recent research has shown microperimetry to be more representative of the macular function in macular diseases. SUMMARY: Microperimetry is currently the clinical investigation of choice to assess residual visual functions and functional vision in macular degenerative diseases, especially geographic atrophy. There is an increasing popularity to employ microperimetry in clinical trials investigating new treatments for geographic atrophy, as well as other macular degenerative diseases, as a reliable functional outcome measure.

Outcomes after giant peripheral retinotomy and anterior flap retinectomy for rhegmatogenous retinal detachments with advanced proliferative vitreoretinopathy using small gauge vitrectomy.

PURPOSE: To analyze the visual and anatomical outcomes for eyes with rhegmatogenous retinal detachment (RRD) and advanced proliferative vitreoretinopathy (PVR) undergoing giant peripheral retinotomy (GPR) using 25-gauge pars plana vitrectomy (PPV). METHODS: In this retrospective multi-center study, patients with RRD with either anteroposterior or circumferential retinal shortening and advanced PVR requiring more than 90-degree GPR with/without relaxing retinotomy were included. Subjects of either gender, any age group, and with complete surgical notes were included. Outcome measures of the study included anatomical success (i.e. complete retinal re-attachment) at 6 months using survival analysis, visual outcomes, and post-operative complications. RESULTS: Forty-one eyes of 41 patients (33 males) with a mean age of 44.9 ± 21.4 years were included. At 6 months follow-up, anatomical success was seen in 29 eyes (70.7%) with a cumulative re-attachment rate of 66% (95% confidence interval = 48 = 79%). All re-detachments occurred at ≤6 months with a peak at 4-6 months (n = 9). Twenty-three eyes (56%) achieved ambulatory vision (5/200) or better. Direct perfluorocarbon liquid-silicone oil exchange was performed in 20 eyes. Intra-operative complications included persistent retinal folds (2 eyes), subretinal air (1 eye), and subretinal bleed (1 eye). Eleven eyes (26.8%) developed secondary glaucoma (2 eyes required a drainage device), and hypotony of ≤6 mmHg was noted in 3 eyes (7.3%). Corneal decompensation was noted in 8 eyes (19.5%), and 3 eyes (7.3%) underwent re-surgery for re-RRD. CONCLUSION: After GPR using small gauge PPV, two-thirds achieve anatomical success, and over half have ambulatory vision, but overall post-operative complications can occur in more than half of the eyes.

Cauda equina syndrome as the initial presentation of uveal melanoma metastasis.

PURPOSE: Uveal melanoma extension to the central nervous system (CNS) is exceedingly rare, and can occur through optic nerve invasion. We report a rare clinical case that presented with cauda equina syndrome as the initial manifestation of metastasis of choroidal melanoma, and showed neurotropic extension by histopathology. Our patient did not demonstrate any evidence of systemic metastasis otherwise. OBSERVATIONS: A 60-year-old male patient with treated choroidal melanoma in his right eye, with presumed clinical control, developed radiation-induced neovascular glaucoma refractory to medical therapy. The eye required enucleation for pain control. One month post-enucleation, he presented to the emergency department with severe abdominal pain, urine retention, constipation, and leg weakness. Magnetic resonance imaging (MRI) of the spine showed extensive leptomeningeal involvement along the entire spinal cord and the cauda equina. On further inquisition, the patient noted prior visual field defect in the contralateral eye. Brain MRI revealed intracranial metastasis with chiasmal involvement. The patient underwent radiotherapy for the brain and spine to improve his symptoms, and was ultimately transferred to palliative care. CONCLUSION AND IMPORTANCE: Optic nerve invasion in uveal melanoma may lead to neurotropic spread of melanoma cells with risk of intracranial and spinal cord metastasis. Neurological symptoms should raise the suspicion of clinicians regarding this complication, which is associated with increased melanoma-related mortality.

NOVEL SURGICAL TECHNIQUE TO REMOVE RETAINED SUBFOVEAL PERFLUOROCARBON LIQUID.

PURPOSE: To describe a novel surgical technique to remove retained subfoveal perfluorocarbon liquid (PFCL). METHODS: After setting up for 23-G pars plana vitrectomy, a 38-G flexible-tip macular hydrodissection cannula connected to the automated viscous fluid infusion kit was used to create a small retinotomy approximately 700 µm to 800 µm inferior to the fovea and induce macular detachment involving the retained PFCL bubble. The flexible cannula was bent at its junction with the shaft and was carefully advanced through the same retinotomy into the subretinal space to access and directly aspirate the retained subfoveal PFCL bubble. Fluid-air exchange was then performed, and surgery was concluded. RESULTS: The retained subfoveal PFCL bubble was successfully removed with restoration of normal foveal architecture on optical coherence tomography and with objective and subjective improvement of central vision. CONCLUSION: We report a novel surgical technique combining macular detachment with direct aspiration of the retained subfoveal PFCL without direct perforation of the foveal center. This technique may provide an alternative approach to manage this difficult complication.

Surgical management of submacular hemorrhage: experience at an academic Canadian centre.

OBJECTIVE: To report the anatomical and visual outcomes of patients with thick submacular hemorrhage (SMH) treated with pars plana vitrectomy (PPV), subretinal tissue plasminogen activator (t-PA), and pneumatic displacement. DESIGN: Single-centre, retrospective case series. PARTICIPANTS: A total of 99 eyes of 99 consecutive patients with thick SMH secondary to any underlying etiology treated with PPV with subretinal t-PA and pneumatic displacement by 6 vitreoretinal surgeons at St. Michael's Hospital, Toronto, between July 2004 and August 2016. METHODS: All medical records and colour fundus photographs were reviewed for data collection. Blood displacement was evaluated at follow-up visits and classified as complete, partial, or none. Main outcome measures included blood displacement at final follow-up, postoperative Snellen best-corrected visual acuities (BCVA), and complication and recurrence rates. RESULTS: Patients had a mean age of 77.7 ± 12.3 years and were followed up for an average of 18.4 ± 22.3 months. Wet age-related macular degeneration was the most common etiology associated with thick SMH (80.8%). Complete blood displacement was observed by final follow-up in 85.9% of the cases, partial displacement in 12.1%, and none in 2.0%. Mean logMAR BCVA improved from 2.03 ± 0.81 (Snellen 20/2143) at baseline to 1.80 ± 1.00 (Snellen 20/1262; p = 0.009) at final follow-up, and baseline BCVA was a significant predictor of final BCVA (p < 0.001). Early postoperative complications included vitreous hemorrhage in 13 eyes and rhegmatogenous retinal detachment in 8. Recurrent SMH was observed in 12 cases. CONCLUSIONS: Vitrectomy with subretinal t-PA and pneumatic displacement seems to be an effective treatment for SMH in terms of blood displacement and visual outcomes.

Primary (Month-6) Outcomes of the STOP-Uveitis Study: Evaluating the Safety, Tolerability, and Efficacy of Tocilizumab in Patients With Noninfectious Uveitis.

PURPOSE: To report the primary endpoint analyses of the safety and efficacy of 2 different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Randomized, controlled, multicenter clinical trial. METHODS: STOP-Uveitis is a randomized, open-label safety, efficacy, and bioactivity clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with noninfectious uveitis (NIU). Thirty-seven patients with NIU were randomized into one of 2 treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Primary outcome measure was incidence and severity of systemic and ocular adverse events through month 6. Secondary outcome measures included mean change in visual acuity (VA), vitreous haze (VH), and central macular thickness (CMT) at month 6. RESULTS: A total of 37 patients were randomized in the study. At month 6, 43.5% of patients who had the potential for a 2-step decrease in VH demonstrated a 2-step decrease (40% in Group 1 and 46.1% in Group 2). Mean change in CMT was -83.88 ± 136.1 µm at month 6 (-131.5 ± 41.56 µm in Group 1 and -38.92 ± 13.7 µm in Group 2). Mean change in VA was +8.22 ± 11.83 ETDRS letters at month 6 (10.9 ± 14.6 in Group 1 and 5.5 ± 7.8 in Group 2). Repeated infusions of TCZ were well tolerated. CONCLUSIONS: Repeated IV administrations of TCZ are well tolerated. TCZ (both 4 and 8 mg/kg) is effective in improving VA and reducing VH and CMT in eyes with noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

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.

Pharmacologic Vitreolysis in Vascular Diseases of the Retina.

Vascular diseases of the retina such as diabetic retinopathy and vascular occlusions account for a large proportion of visual morbidity and blindness worldwide. The role of vitreous in the pathogenesis of these conditions has been increasingly recognized. Despite advances in the surgical technique of pars plana vitrectomy, the use of intravitreal agents for the lysis of vitreous has received attention, guided largely by promising results from the trials involving patients with non-vascular retinal diseases such as vitreomacular traction. The purpose of this review is to provide a comprehensive summary of the present knowledge on pathophysiologic basis of pharmacologic vitreolysis and its efficacy in vascular diseases of the retina. A review of completed and ongoing clinical trials will be presented, along with insights into future directions of this therapy.

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.

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.

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.

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.

Structural Characteristics of Retinal Layers Adjacent to Geographic Atrophy.

BACKGROUND AND OBJECTIVE: To compare the anatomy of different retinal layers adjacent to areas of geographic atrophy (GA) to those of eyes with no known ocular diseases. PATIENTS AND METHODS: Spectral-domain optical coherence tomography (SD-OCT) scans from eyes with GA were retrospectively reviewed. Two scans with no findings suggestive of GA changes on OCT were selected from immediately above and/or below the edge of the lesions. Thickness values of the retinal layers were calculated and compared to values obtained from normal subjects. RESULTS: Forty-four eyes (30 patients) were compared to 20 healthy eyes. Retinal pigment epithelium (RPE), inner nuclear layer (INL), and full retinal thickness (FRT) values were significantly lower in patients compared to healthy subjects. Thicknesses of all other layers were not significantly different. CONCLUSION: Clinically appearing, non-involved RPE and INL layers of eyes with GA demonstrate significant thinning compared to corresponding layers in eyes with no known ocular diseases.

Combined systemic and ocular chemotherapy for anterior segment metastasis of systemic mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive subtype of non-Hodgkin's lymphoma that rarely metastasizes to the iris and the anterior segment. Blastic/pleomorphic morphology is thought to have an adverse effect on prognosis in MCL. MCL is resistant to conventional chemotherapeutic regimens with a tendency for multiple relapses. Management of anterior segment metastasis of systemic MCL has not been described in literature. FINDINGS: A 58-year-old male presented with an aggressive, relapsing, metastatic, systemic blastic variant of MCL with ocular involvement. At the time of initial presentation, large tumor cells were visible in the anterior chamber (AC) along with hypopyon and fibrin. The AC cells stained positively for CD20. The iris was thickened and coated with lymphoma cells. Iris neovascularization was present. Given extensive systemic and ocular involvement, the patient was given combination chemotherapy with systemic ibrutinib and intravitreal injections of methotrexate and rituximab. The disease response was monitored using multimodal imaging, including anterior segment optical coherence tomography and ultrasound biomicroscopy. Following combination of systemic and intraocular chemotherapy, there was a marked decrease in the ocular tumor load and the systemic disease. CONCLUSIONS: Combination therapy with intravitreal injections of chemotherapeutic agents targeting monoclonal B-cell population and novel systemic agents may help to achieve remission in anterior segment metastasis of aggressive subtypes of NHL such as blastic variant of MCL. Multimodal imaging may assist in the management of these cases.