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Background To evaluate spectral domain optical coherence tomography (SD-OCT) findings as biomarkers in primary central nervous system lymphoma (PCNSL) with or without ocular involvement. Methods This study was a cross-sectional study and patients with a confirmed diagnosis of PCNSL with or without ocular involvement were included. Patient cohort finder tool was used to identify patients with lymphoma using ICD-10 codes (C82–C88), from January 2004 to October 2017. A total of 14,820 patients were identified. Procedure code (92134) for optical coherence tomography (OCT) was then applied to identify patients who had underdone OCT imaging at ophthalmology clinic. Clinic charts of 460 patients with lymphoma and available OCT were reviewed to identify patients with confirmed diagnosis of PCNSL and divided into two groups (Group 1: with and Group 2: without ocular involvement). OCT scans of patients in both study groups were analyzed for the presence of (1) Hyperreflective deposits in choroid, retinal pigment epithelium (RPE), outer and inner retina; (2) RPE thickening; (3) Vitreous debris; (4) Intraretinal fluid; (5) Ellipsoid zone disruption by masked graders. Chi-square was used to analyze the difference between the groups. Results Twenty-two eyes (11 patients) with PCNSL were included this study (Group 1: 6 eyes and Group 2: 16 eyes). Mean age of subjects was 65 years. Five patients (45.45%) were female. There was no statistically significant difference between the groups for the presence of hyperreflective deposits in choroid, RPE, outer and inner retina, and presence of RPE thickening, intraretinal fluid, and ellipsoid zone disruption. Vitreous debris was found more commonly in group 1 subjects (83%) than group 2 (31.25%) (p = 0.029). All subjects in both groups showed hyperreflective deposits in the RPE demonstrating RPE infiltration. However, RPE thickening was noted only in 3 patients (Group1: 1 and Group2: 2). Conclusions OCT finding of hyperreflective deposits present in eyes with lymphoma secondary to PCNSL are also observed in eyes with PCNSL without ocular disease. However, the vitreous deposits are more commonly found in eyes with ocular disease. These hyperreflective deposits can serve as biomarkers for early detection of ocular involvement by PCNSL.

To identify baseline characteristics of subjects enrolled in the READ-3 study that would predict the response of macular edema to ranibizumab (RBZ) therapy at year 1. In this post hoc analysis of the READ-3 randomized, multicenter phase 2 clinical trial, subjects with diabetic macular edema (DME) were randomized to receive monthly intravitreal injections of RBZ (0.5 or 2.0 mg) for 6 consecutive injections followed by as-needed treatments based on pre-defined retreatment criteria. In this sub-study, subjects were divided into three groups (persistent, rebound, and resolved) based on edema status at month 12 (M12). Multi-logistic regression was utilized to assess the probability of edema outcomes M12, based on the baseline characteristics. One hundred twenty-three out of 152 subjects were analyzed for this sub-study. A significant difference was observed in the baseline (BL) central subfield thickness (CST) among the study groups (p 80% probability of the subject having persistent edema if BL CST was > 570 μm (p 80% probability of edema persistence at CST > 570 μm [RR, 1.006; p 0.05). Subjects with high CST (> 570 μm) at baseline may not benefit from repeated intravitreal injections of anti-VEGF for resolution of edema.

Purpose To compare laser flare photometry (LFP) measurements of aqueous flare with Standardization of Uveitis Nomenclature (SUN) and modified SUN grading. Methods In this prospective study with multicenter design, uveitis patients were classified according to SUN and modified SUN grading scales. LFP was performed with Kowa FM-700 flaremeter. Mean LFP values were compared with SUN and MSUN scores. Results The study included 475 LFP measurements, of which 216, 48, 150, 31, 28 and 2 had 0, 0.5+, 1+, 1.5+, 2+ and 3+ flare, respectively. LFP values were significantly different between each two consecutive steps for both clinical gradings (all P < .05). Cut-off values for modified SUN grading steps were defined as 5.7, 9.7, 15.7 and 43.2 for 0/0.5+, 0.5+/ 1+, 1+/1.5+ and 1.5/2+ borders of clinical flare, respectively. Conclusions LFP proves to be an objective measurement in analyzing aqueous flare comparable to both SUN and MSUN clinical grading systems.

Purpose To correlate the findings of retinal function with multifocal electroretinogram (mfERG), microperimetry (MP), and structural assessments with spectral-domain optical coherence tomography (SD-OCT) in topographically corresponding areas of the macula of patients with birdshot chorioretinopathy (BSCR). Methods Patients diagnosed with BSCR by clinical and imaging findings were included in the study. The mfERG was performed using 61 hexagon stimulus patterns grouped into 5 rings (Diagnosys Inc., USA). Individual responses [N1-P1 amplitudes in nanovolt (NV)/degree2 and P1 implicit time in milliseconds (msec)] for each hexagon in the central 3 rings (R1, 0°–2.3°; R2,2.3°–7.7°; and R3, 7.7°–12°) were obtained (19 hexagons). MP examination consisted of Polar 3–12° test with 28 points in 3 concentric rings with diameters of approximately 2.3°, 6.6°, and 11.1° from the foveal center. SD-OCT was performed using macular scans of 20° × 20°. The retinal sensitivity values on MP and thickness values of retinal layers were correlated with the responses on the mfERG for each topographically correlated hexagon. Results Sixteen eyes of eight patients were included in the study (mean age, 59.87 ± 10.01 years; range, 41–73 years). The amplitudes and the implicit times on mfERG and retinal sensitivities on MP were decreased for each of the 19 hexagons. Considering retinotopically matched points, there was correlation between the retinal sensitivities and mfERG implicit times and response amplitudes in all three rings. The thickness of the retinal pigment epithelium showed modest correlation with the mfERG parameters (ρ = 0.29; p = 0.04). The structural changes on SD-OCT, such as IS-OS disruption, were associated with changes in the mfERG trace arrays. Conclusions The structural and functional assessments in retinae of eyes with BSCR suggest that each imaging tool may be capturing unique aspects of retinal dysfunction. Multimodal imaging may allow detailed analyses of retinal damage at various corresponding loci. These findings are important when considering the use of these techniques in BSCR.

Background The ETDRS stereoscopic seven-field (7F) has been a standard imaging and grading protocol for assessment of diabetic retinopathy (DR) severity score in many clinical trials. To the best of our knowledge, the comparison between montage and stereoscopic 7F has not been reported in the literature. Therefore, the main purpose of this study is to compare agreement between montage and stereoscopic seven-field (7F) photographs in the assessment of DR severity. Methods Stereoscopic 7F photographs were captured from subjects with DR. Montages of monoscopic 7F images were created using Adobe Photoshop CS6 Extended©. The best quality image of each stereo pair was selected and placed on a 150 × 125-inch canvas field according to the standard location from field 1 to 7. All the fields were aligned following the vessels and overlaid using the built-in blending tool. The resulting montage was utilized for grading and compared with grading on stereoscopic 7F photographs. Three independent graders were asked to assess DR severity on stereoscopic 7F photographs and montage. Severity level agreement between stereo 7F and montage was cross-tabulated and the agreement of DR severity levels between stereoscopic 7-field images and montage was analyzed using κ intergrader agreement; statistical significance was set at p Results A total of 50 eyes were included in the study. There was a substantial agreement between stereoscopic 7F and montage (κ = 0.745, κweighted = 0.867) in assessment of DR severity. Of 50 eyes, 80% of the cases showed complete agreement, and 100% of the cases had agreement within one-step. There was a moderate agreement among graders, and κ-value ranged from 0.4705 to 0.5803. Conclusion In this study, we found a substantial agreement in assessing DR severity score employing non-stereoscopic montage and stereoscopic 7F photographs.

Background/aimsTo use a composite endpoint scoring system in assessing efficacy of two doses of intravenous tocilizumab (TCZ), in eyes with non-infectious uveitis.MethodsData from STOP-Uveitis Study (a phase 2 multicentre, randomised, interventional clinical trial), where monthly intravenous infusions of 4 mg/kg (Group 1) or 8 mg/kg (Group 2) TCZ until month 6 (M6) were administered, were used. Efficacy was ascertained by a composite endpoint scoring system consisting of: (1) visual acuity; (2) intraocular inflammation; (3) central retinal thickness; (4) posterior segment inflammation on fluorescein angiographic and (5) steroid taper. Each component of grading system was graded as ((+1) improvement, (−1) worsening or (0) no change) based on specific criteria. The clinical response was classified as positive (improvement in at least one parameter and worsening in none), negative (worsening of any parameter) or stable (neither improvement nor worsening of any parameter). The percentage achieving various clinical responses was compared between groups.ResultsThirty-seven patients were analysed. At M6, 31 (83.8%) subjects demonstrated a positive clinical response (Group 1=14 (77.8%) and Group 2=17 (89.5%)). Three (8.1%) subjects (all Group 1) met the criteria for treatment failure, whereas three (8.1%) subjects showed a stable clinical response (Group 1=1 and Group 2=2). The difference in clinical responses between study groups was not significant (p>0.05).ConclusionsBoth doses of intravenous TCZ were effective in either improving or maintaining stability in patients using the composite endpoint scoring system. A composite scoring system as used in this study may be a better measure to assess efficacy outcomes as compared with only vitreous haze or other single outcome measures.

Background Uveitis consists of a spectrum of inflammatory disorders characterized by ocular inflammation. The underlying pathophysiology consists of a complex interplay of various inflammatory pathways. Interleukin 6 is an important mediator of inflammation in uveitis and constitutes focus of research toward development of newer biological therapies in the management of non-infectious uveitis. Main body Pan-blockade of the inflammatory pathways with steroids is generally the first step in the management of acute non-infectious uveitis. However, long-term therapy with steroids is associated with systemic and ocular side effects, thereby necessitating the need for development of steroid sparing agents. IL-6 is a cytokine produced by various immune cells, in response to molecular patterns and affects multiple inflammatory cells. In particular, IL-6 is involved in differentiation of CD-4 cells into Th-17 cells that have been shown to play a significant role in various immune-mediated diseases such as uveitis. This broad-spectrum immunomodulatory activity makes IL-6 an excellent target for immunomodulatory therapy. Tocilizumab was the first IL-6 inhibitor to demonstrate efficacy in humans. It inhibits IL-6 from binding to both membrane-bound and soluble receptor and can be administered via intravenous (IV) and subcutaneous (SC) routes. It has been FDA approved for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Following the approval in systemic diseases, its efficacy was demonstrated in various uveitis studies including a phase 2 clinical trial (STOP-Uveitis). Overall, tocilizumab has shown a good safety profile with the risk of malignancy consistent with that expected in patients with rheumatoid arthritis. However, tocilizumab therapy has been shown to increase the risk for gastrointestinal perforation and dose-dependent neutropenia. Following the success of tocilizumab, several other agents targeting the IL-6 pathway are in the pipeline. These include sirukumab, siltuximab, olokizumab, clazakizumab, and EBI-031 which target IL-6; Sarilumab and ALX-0061 act on the IL-6 receptor. Conclusion Studies have shown that IL-6 inhibitors can be effective in the management of NIU. In addition, the levels of IL-6 are elevated in other ocular vascular diseases such as retinal vein occlusion and diabetic macular edema. The roles of IL-6 inhibition may be broadened in the future to include the management of retinal vascular diseases and non-uveitic macular edema.

Purpose: To investigate the use of software-generated corrections in neutralizing perceived distortions in age-related macular degeneration. Methods: A tablet-based application was utilized to elicit distortions. Five subjects (seven eyes: neovascular age-related macular degeneration and three eyes: non-neovascular age-related macular degeneration) traced the reference lines, and their distortion traces were recorded. To counter distortion, a software-generated trace was re-traced by subjects to produce a corrected trace. Final traces were superimposed on optical coherence tomography images and following distances calculated: (a) dDT: distance between distortion trace and reference line; (b) dGT: distance between software-generated trace and corrected trace; (c) dCT: distance between corrected trace and reference line. Mean percent improvement in distortion was reported. Mean effectiveness of correction was also reported by utilizing t test to compare dDT and dCT. The number of distortion traces with underlying lesions on optical coherence tomography was also analyzed. Results: Mean age of the subjects was 76.6 (±9.5) years. Each patient traced six reference lines and each was considered a separate case. Out of 30 cases, 17 (56.6%) elicited distortion. Mean percent improvement in distortion was 71.3 ± 23% ( p Conclusion: Software-generated corrections can potentially correct for perceived distortions in patients with age-related macular degeneration, especially in cases with preserved photoreceptor layer.

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.

Purpose To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME). Design Randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial. Participants A total of 152 patients (152 eyes) with DME. Methods Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n = 77) or 2.0 mg (n = 75) RBZ. Study eyes received 6 monthly mandatory injections followed by as-needed injections until month 24. Main Outcome Measures The primary efficacy end point of the study was mean change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at month 6. Secondary outcomes included the mean change in BCVA and CFT at month 24, and incidence and severity of systemic and ocular adverse events through month 24. Results A total of 152 eyes were randomized in the study. At month 24, the mean improvement from baseline BCVA was +11.06 letters in the 0.5 mg RBZ group (n = 59) and +6.78 letters in the 2.0 mg RBZ group (n = 54) ( P = 0.02). The mean numbers of RBZ injections through month 24 were 18.4 and 17.3 in the 0.5 mg and 2.0 mg RBZ groups, respectively ( P = 0.08). The mean change in CFT was −192.53 μm in the 0.5 mg RBZ group and −170.64 μm in the 2.0 mg RBZ group ( P = 0.41). By month 24, 3 deaths had occurred in the 0.5 mg RBZ group and 3 deaths had occurred in the 2.0 mg RBZ group; 5 of these 6 deaths occurred secondary to cardiovascular causes, and 1 death occurred as the result of severe pneumonia. All 5 patients with a cardiovascular cause of death had a history of coronary heart disease. Conclusions At month 24, there were significant visual and anatomic improvements in both groups, with subjects in the 0.5 mg RBZ group gaining more vision. Visual and anatomic gains achieved at month 6 were largely maintained through month 24. No new safety events were identified. In this study population, 2.0 mg RBZ does not appear to provide additional benefit over 0.5 mg RBZ.

To identify baseline characteristics of subjects enrolled in the READ-3 study that would predict the response of macular edema to ranibizumab (RBZ) therapy at year 1.In this post hoc analysis of the READ-3 randomized, multicenter phase 2 clinical trial, subjects with diabetic macular edema (DME) were randomized to receive monthly intravitreal injections of RBZ (0.5 or 2.0 mg) for 6 consecutive injections followed by as-needed treatments based on pre-defined retreatment criteria. In this sub-study, subjects were divided into three groups (persistent, rebound, and resolved) based on edema status at month 12 (M12). Multi-logistic regression was utilized to assess the probability of edema outcomes M12, based on the baseline characteristics.One hundred twenty-three out of 152 subjects were analyzed for this sub-study. A significant difference was observed in the baseline (BL) central subfield thickness (CST) among the study groups (p0.05). BL CST was a significant predictor for edema outcome at M12 with80% probability of the subject having persistent edema if BL CST was570 μm (p0.05). This association persisted when controlled for the dose of RBZ (relative risk (RR), 1.007; p0.05). BL CST was also a significant predictor for having persistent edema at M12 in subjects without vitreomacular adhesion (VMA) (80% probability of edema persistence at CST570 μm [RR, 1.006; p0.05]). However, in the presence of VMA, BL CST was no longer a significant predictor of having persistent edema at month 12 (RR, 1.005; p0.05).Subjects with high CST (570 μm) at baseline may not benefit from repeated intravitreal injections of anti-VEGF for resolution of edema.

Purpose The aim of this study is to evaluate the differences in the fundus autofluorescence (FAF) signal between the blue light autofluorescence (BAF) from Spectralis® (Heidelberg, CA) and green light autofluorescence (GAF) 200TxTM (OPTOS, UK, in normal subjects and in patients with retinochoroidopathies (RC). Methods In this prospective study, FAF was performed using BL (λ = 488 nm) and GL (λ = 532 nm) on normal subjects and patients with RC. The corresponding pairs of BAF and GAF images from both groups were analyzed using Photoshop. The strength of the FAF signal was measured on a gray scale, where optic disc was a standard to indicate absence of AF. In addition, gray values obtained from three identical points (foveal center, and points of hypo and hyper autofluorescence) in the corresponding BAF and GAF images of normal and RC subjects were divided by the optic disc value to calculate autofluorescence signal ratio (R). The R values at fovea (R1), hypoautofluorescent point (R2), and hyperautofluorescent point (R3) were compared between BAF and GAF modalities, in normal and in RC subjects separately. Results One hundred six pairs (106 eyes) of FAF images analyzed (37 pairs: normal and 69 pairs: RC subjects). In normal subjects, the mean R1, R2, and R3 values for BAF were (1.5 ± 0.88, 1.23 ± 0.58, and 4.73 ± 2.85, respectively) and for GAF were (0.78 ± 0.20, 0.78 ± 0.20, and 1.62 ± 0.39, respectively). Similarly, in subjects with RC, the mean R1, R2, and R3 values for BAF were (1.68 ± 1.02, 1.66 ± 1.15, and 7.75 ± 6.82, respectively) and for GAF were (0.95 ± 0.59, 0.79 ± 0.45, and 2.50 ± 1.65, respectively). The mean difference in the R1, R2, and R3 ratios between BAF and GAF in normal and in RC subjects was statistically significant (p 0.05). Conclusion The distribution and intensity of the AF signal differ in BAF and GAF and cannot be used interchangeably. In BAF, optic disc signal is always weaker than in other areas, which was not true for GAF where optic disc signal was stronger than fovea and hypoautofluorescent point in both groups.

Purpose: To evaluate spectral domain optical coherence tomography (SD-OCT) findings as potential biomarkers in primary central nervous system lymphoma (PCNSL) with or without ocular involvement. Methods: The patient cohort finder tool at Stanford University Hospital was used to identify patients with any type of lymphoma using the ICD-10 codes (C82-C88), from January 2004 to October 2017. A total of 14,820 patients were identified. Procedure code (92134) for optical coherence tomography (OCT) was then applied to identify patients who underwent OCT at the ophthalmology clinic/Byers Eye Institute. Clinic charts of 460 patients with lymphoma who had undergone OCT were reviewed to identify patients with confirmed diagnosis of PCNSL and divided into two groups (Group 1: with and Group 2: without ocular involvement). Their SD-OCTs from within 1 month of the diagnosis were analyzed for the presence of 1) Hyperreflective deposits in choroid, retinal pigment epithelium (RPE), outer retina and inner retina; 2) RPE thickening; 3) Vitreous debris; 4) Intraretinal fluid; 5) Ellipsoid zone disruption by masked graders. Chi-square was used to analyze the difference in characteristics between the groups. Results: Twenty-two eyes of 11 patients with PCNSL were included this study (6 eyes in group 1 and 16 eyes in group 2). Mean age of subjects was 65 years (Group1: 60 years and Group 2: 67 years). Five patients (45.45%) were female (Group1: 3 and Group2: 7). There was no statistically significant difference between the groups for the presence of hyperreflective deposits in choroid, RPE, outer and inner retina, and the presence of RPE thickening, intraretinal fluid and ellipsoid zone disruption. Vitreous debris was found more commonly in group 1 subjects (83%) than group 2 (31.25%) (p=0.029). All subjects in both groups showed hyperreflective deposits in the RPE demonstrating RPE infiltration. However, RPE thickening was noted only in 3 patients (Group1: 1 and Group2: 2). Conclusions: Our study has demonstrated that the OCT findings of hyperreflective deposits present in eye with IOL secondary to PCNSL are also observed in eyes with PCNSL without ocular disease. These hyperreflective deposits can serve as biomarkers and aid in the early detection of ocular involvement by PCNSL. Funding Statement: "No funding was received for this project" Declaration of Interests: QDN is a recipient of a Physician Scientist Award from Research to Prevent Blindness, New York, NY, and serves on the Scientific Advisory Board for AbbVie, Bayer, Genentech, Regeneron, and Santen, among others. No other authors have received any financial funding or support. The Byers Eye Institute has received research funding support from Research Prevent Blindness, Inc. Ethics Approval Statement: It was conducted in compliance with the Declaration of Helsinki, the United States Code of Federal Regulations Title 21, and the Harmonized Tripartite Guidelines for Good Clinical Practice (1996). The study was approved by local institutional review board. An informed consent waiver was obtained as charts of the selected patients were reviewed retrospectively.

The authors have retracted this article [1] for legal reasons. Therefore the contents of this article are no longer available. The authors have been invited to submit a new version of the article. All authors have agreed to this retraction.

Purpose To describe the presentation, clinical course and management of a patient with posterior hypopyon secondary to atypical (fungal) endogenous endophthalmitis. Observations A 55-year-old Asian Indian female presented with decreased vision in the left eye (OS). The best-corrected visual acuity was 20/20 in the right eye (OD) and counting fingers (CF) in the left eye (OS) at the time of initial presentation. Slit-lamp examination revealed 1+ cells and 1+ flare in the anterior chamber of OS. Clinical examination and imaging assessment with fundus photography revealed vitritis, a posterior hypopyon and retinal exudates. The patient had an episode of fever one month before presentation for which an intravenous dextrose infusion was administered. After carefully evaluating the patient, ocular images, detailed history and necessary laboratory tests, a working diagnosis of endogenous endophthalmitis was reached. Empirical treatment with topical and systemic antibiotics, and topical cycloplegics and steroids was initiated. Therapeutic and diagnostic pars plana vitrectomy (PPV) was subsequently performed; microbiology and cytology analyses revealed evidence of fungal elements. Therefore, systemic anti-fungal treatment was initiated; the patient demonstrated significant clinical improvement with good visual outcome. Conclusion and importance Posterior hypopyon in endophthalmitis is a rarely observed entity and is typically obscured due to dense vitritis. Such clinical manifestation may suggest a possible infectious etiology as described in this case.

Background Vessel flow density (VFD) may provide important information regarding perfusion status. Diurnal variation in VFD of choriocapillaris has not been reported in literature. In the index study, optical coherence tomography angiography (OCTA) was used to assess the diurnal variation of the VFD in the choriocapillaris of subjects with no known ocular disease. Methods Fifty eyes with no known ocular disease (25 subjects) were included. OCTA images were acquired using AngioVue (Optovue, Fremont, CA, USA) at two different time points on a single day: 9:00 AM and 6:00 PM. Macular cube scan protocol (3 × 3 mm) centered on the fovea was used. Automatic segmentation of the retinal layers and choriocapillaris was performed using ReVue software, which was also used to measure the choriocapillaris VFD. Horizontal line scan passing through fovea was obtained by the device at both time points to measure the subfoveal choroidal thickness (CT). Linear measurement tool of software was used to measure subfoveal CT according to a standardized reproducible method. Wilcoxon signed-rank test was used to assess the differences in choriocapillaris VFD and subfoveal CT at the two time points. Correlation between change in choriocapillaris VFD and subfoveal CT at the two time points was assessed using the Pearson correlation coefficient (r). Results The mean age of the subjects was 31.96 ± 11.23 years. Choriocapillaris VFD was significantly higher at 9:00 AM compared to 6:00 PM (P

Uveitis represents a spectrum of diseases characterized by ocular inflammation that leads to significant visual loss if left untreated. Adequate, long-term control of inflammation with minimal systemic and local adverse effects is the preferred strategy for treating patients with uveitis. Pharmacotherapy for uveitis consists mainly of corticosteroids in various formulations such as topical, local, intraocular and systemic. However, monotherapy with corticosteroids is often unacceptable due to serious adverse effects on various organ systems. There exist limitations with the use of steroid-sparing systemic immunosuppressive agents, as these medications may have significant adverse events and a narrow therapeutic window. Thus, newer molecular targets that act on various steps of the inflammatory pathway appear to be promising emerging strategies for treating uveitis. Specially designed monoclonal antibodies in development can potentially halt the inflammatory processes resulting in remission of the disease. In the index review, novel molecular agents and biological therapies that have shown promising efficacy and safety data in preclinical and clinical studies have been summarized. In addition, new drug delivery systems that may ensure high intraocular therapeutic levels of pharmacologic agents have been highlighted.

Fundus autofluorescence (FAF) is a relatively new but valuable imaging tool for multiple anatomical and physiological alterations in the ocular tissue secondary to inflammation, especially in posterior uveitis. FAF is the scale on which the health and function of the retinal pigment epithelium (RPE) can be measured. Essentially, FAF is a map of distribution of lipofuscin, which is the autofluorescent pigment of the eye, comprising of several types of fluorophores. Lipofuscin is naturally found in RPE due to photoreceptor outer segment turnover by RPE regularly. However, its excessive accumulation in the outer retina and neurosensory layer is observed in pathological processes.

Retinal vasculitis presents with inflammation involving the retinal vasculature as an isolated disease or in combination with other ocular or systemic conditions. This entity may be associated with a wide variety of clinical manifestations such as vascular sheathing, cotton-wool spots, retinal ischemia, and neovascularization. Often, retinal vasculitis and its complications lead to diagnostic challenges in identifying the exact etiology of the inflammation. Ancillary investigations such as fundus photography, fluorescein angiography, and more recently, adaptive optics imaging and optical coherence tomography angiography, may provide valuable information that help in establishing the exact diagnosis and initiation of appropriate therapy. In the index review, multimodal imaging features of retinal vasculitis are described. In addition, detection of vascular inflammation using novel noncontact imaging techniques has been highlighted.

During the past decade, significant advances have occurred in the management of neovascular age-related macular degeneration (NV-AMD). The advent of anti-vascular endothelial growth factor (anti-VEGF) therapy has shifted the treatment goal of NV-AMD from merely salvaging vision to improving visual acuity and maintaining a good quality of life. Aflibercept (AFL) is a significant addition to the arsenal of anti-VEGF therapies against the NV-AMD. In the index review, pharmacology and efficacy of AFL has been reviewed.An extensive literature search was performed to identify preclinical and clinical studies performed to illustrate the role of AFL in NV-AMD. Randomized clinical trials evaluating other anti-VEGF agents were also included for comparison. Additionally, studies where AFL was employed to treat anti-VEGF-resistant cases agents have been reviewed.AFL is an effective agent in the management of NV-AMD and its efficacy has been found to be comparable to ranibizumab (RBZ). Additionally, AFL is a good alternative agent in patients with NV-AMD resistant to RBZ and bevacizumab (BVZ), and can potentially lessen the treatment burden. As more research is conducted, the role of AFL in varying dosing regimens, as monotherapy and in combination with other agents, will become further defined.

Chronic inflammation plays an important role in the pathogenesis of ocular diseases such as diabetic retinopathy, uveitis and age-related macular degeneration. Activation and proliferation of naïve T cells may result in pathological changes responsible for significant visual morbidity. Sirolimus (earlier termed rapamycin) is a novel drug that inhibits cellular kinases and, thereby, inhibits T-cell proliferation. Preclinical studies in experimental models have shown promising results with the use of this pharmacological agent in various ocular conditions. Subsequently, early phase I/II studies have provided encouraging safety and efficacy data. This chapter focuses on the mechanisms of action, preclinical study results and data from human clinical trials of sirolimus in human eye diseases. Key highlights from ongoing phase III clinical trials are also provided. Sirolimus, thus, appears to be an important addition to the armamentarium of steroid-sparing therapeutic agents that act on various steps in the inflammatory pathway.

Chronic inflammation plays an important role in the pathogenesis of ocular diseases such as diabetic retinopathy, uveitis and age-related macular degeneration. Activation and proliferation of naive T cells may result in pathological changes responsible for significant visual morbidity. Sirolimus (earlier termed rapamycin) is a novel drug that inhibits cellular kinases and, thereby, inhibits T-cell proliferation. Preclinical studies in experimental models have shown promising results with the use of this pharmacological agent in various ocular conditions. Subsequently, early phase I/II studies have provided encouraging safety and efficacy data. This chapter focuses on the mechanisms of action, preclinical study results and data from human clinical trials of sirolimus in human eye diseases. Key highlights from ongoing phase III clinical trials are also provided. Sirolimus, thus, appears to be an important addition to the armamentarium of steroid-sparing therapeutic agents that act on various steps in the inflammatory pathway.

Diabetic macular edema (DME) secondary to diabetic retinopathy (DR) is a major cause for functional visual loss in the developed world. Laser photocoagulation has been used for decades in the treatment of DME. However, the advent of anti-vascular endothelial growth factor (anti-VEGF) has revolutionized the treatment of DME. Three important anti-VEGF agents whose efficacy has been well established via phase III clinical trials include ranibizumab, bevacizumab, and aflibercept. However, even in the era of anti-VEGF therapies, there are some challenges that retina specialists have to confront in managing patients with DME. These include the need for frequent treatment and an unpredictable response to therapy. There is evidence to suggest that pathways other than the VEGF pathway may be playing a role in the development of DME. Thus, extensive research is focused on development of novel agents that target these pathways. This review focuses on novel therapeutic agents in development, which may be used as a monotherapy or in combination with anti-VEGF agents, for the management of DME in the future.

PURPOSE To evaluate the thicknesses of individual retinal layers, and the correlation between structural changes and functional loss using spectral domain optical coherence tomography (SD-OCT) scans and electroretinograms (ERG), in eyes with autoimmune retinopathy (AIR). METHODS SD-OCT raster scans of 12 eyes from 6 patients serologically diagnosed with AIR were evaluated. Retinal layers were segmented along a 5 mm horizontal scan passing through the fovea. Retinal layers analyzed include full retinal thickness (FRT), retinal pigment epithelium and Bruch's membrane complex (RPE+BM complex), photoreceptor layer (PRL), inner nuclear layer (INL), combined ganglion cell and inner plexiform layers (GCL+), nerve fiber layer (NFL), and combined GCL+ and NFL layers (GCL+/NFL). Changes in the thicknesses of the layers were assessed in 0.5 mm increments along the B-scan in the central, nasal, and temporal regions. These recorded values were compared to corresponding values of 51 eyes from 51 subjects with no known ocular pathology. Full-field ERGs were obtained at corresponding visits and were interpreted by a grader masked to the diagnoses and OCT findings. RESULTS The mean age of the patients was 59.5 years (range, 33-83), with 4 males (66.6%). Within the control population of 51 subjects, mean age was 51.5 years (range, 40-75), with 25 males (49%). Eyes with AIR showed a loss of retinal tissue compared to eyes with no known ocular pathology at the fovea. Specifically, the FRT, RPE+BM complex, and PRL exhibited thinning of statistically significance. ERG findings demonstrated a functional deficit which showed a good correlation with structural loss. Fifty (50) percent of eyes experienced central photoreceptor (rod and cone) dysfunction and 75% of eyes displayed peripheral photoreceptor (rod and cone) dysfunction. CONCLUSIONS Eyes with AIR show a loss of retinal tissue compared to eyes with no known ocular pathology. The greatest loss appears to occur in the RPE and PRL. ERG findings correlate strongly with the loss of tissue seen in these layers. Thus, therapeutic options may be targeted to preserve these regions of the retina.