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Purpose The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center. Design Retrospective, institutional review board–approved study. Participants Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016. Methods Intravitreal injection. Main Outcome Measures Complication occurrence within 15 days of injection. Results From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient’s gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications. Conclusions Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient’s gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes. more...

Objective: To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial. Design: Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial. Participants: Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension. Methods: I brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis. Main Outcome Measures: Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation. Results: As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%–15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%–13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P 0.08). Conclusions: Local treatment failure and enucleation were relatively infrequent events after I brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe. Ophthalmology 2002;109:2197–2206 © 2002 by the American Academy of Ophthalmology. more...

BACKGROUND AND OBJECTIVE: To identify choroidal neovascular membrane (CNVM) associated with spectral-domain optical coherence tomography (SD-OCT)-defined pigment epithelial detachment (PED) using SD-OCT angiography (SD-OCTA). PATIENTS AND METHODS: Sixty-nine patients with same-day OCT and OCTA imaging were reviewed, and 41 eyes of 29 patients with PEDs were included. OCTs were analyzed for PED type, fluid, and subretinal hyperreflective material (SHRM). RESULTS: Twenty-seven eyes (66%) demonstrated CNVM on OCTA beneath all subtypes of PED. Twenty-two eyes (75.9%) with fluid or SHRM demonstrated CNVM on OCTA ( P = .036). Fluid corresponded in a statistically significant manner with treatment ( P = .0032), whereas SHRM did not ( P = .613). OCTA-defined CNVM showed borderline statistically significant correlation to treatment ( P = .05). Increased choroidal flow signal seen in 50% of eyes did not demonstrate statistically significant correlation to the presence of fluid on SD-OCT ( P = .2798) or treatment decision ( P = .678). A subset of 14 untreated eyes with CNVM was analyzed, 21% of which required treatment at subsequent visits. CONCLUSIONS: OCTA-defined CNVM was seen in all subtypes of PED in clinically active and inactive disease. The role of OCTA in predicting need for treatment remains to be established. [ Ophthalmic Surg Lasers Imaging Retina. 2019;50:620–626.] more...

Purpose Although intravitreal anti-vascular endothelial growth factor (VEGF) injection has become the mainstay treatment for neovascular age-related macular degeneration (nAMD), emerging studies suggest that anti-VEGF may be correlated with the development of macular atrophy (MA) in chronic therapy. The purpose of the current study is to determine the prevalence and progression of MA in nAMD treated with chronic anti-VEGF in a routine clinical practice. Design Retrospective cohort. Participants Patients with nAMD who were previously treatment-naive and treated with anti-VEGF at the Cole Eye Institute for at least 4 years. Methods This is chart review on anti-VEGF treated patients with nAMD with baseline and yearly follow-up spectral domain-OCT for at least 4 years. Retinal pigment epithelium subillumination analysis was used to automate identification of atrophy. Segmentation errors were manually corrected by 4 expert raters using a standardized grading protocol to quantify MA size. Patient baseline characteristics and treatment course were analyzed to identify predictive factors for the development of MA. Main Outcome Measures MA growth rate and prevalence in cohorts with and without baseline atrophy. Results A total of 79 eyes from 66 patients (79.8±7.4 years, 63% were female) with nAMD and 4 years of follow-up with anti-VEGF injections were identified. The mean baseline visual acuity was 0.48±0.25 logarithm of the minimum angle of resolution (20/60 Snellen equivalent), and the mean final visual acuity was 0.48±0.49 logarithm of the minimum angle of resolution (20/44 Snellen equivalent, P = 0.23). The average number of injections was 19.8±9.8. MA was observed in 12.7% of eyes at baseline with an average annual growth rate of 0.7±0.5 mm2. In eyes without baseline MA, atrophy developed in 53.6% eyes by year 4 with a growth rate of 0.2±0.4 mm2 per year. Multiple linear regression analysis revealed that the progression of MA was positively correlated with age (R = 0.02, P = 0.009). Conclusions More than half of patients with nAMD treated with anti-VEGF injections for 4 years developed new MA. Atrophy progression was most strongly correlated with age, which suggests that baseline disease characteristics may be more predictive of MA progression than cumulative anti-VEGF treatment. more...

BACKGROUND AND OBJECTIVE: In the ASSESS study, patients with neovascular age-related macular degeneration transitioned from other anti-vascular endothelial growth factor therapies to intravitreous aflibercept (Eylea; Regeneron, Tarrytown, NY) injections (IAI). The purpose was to determine the 36-month outcomes following the change from a fixed 24-month IAI dosing regimen to a routine clinical practice regimen. PATIENTS AND METHODS: Patients were treated with a fixed bimonthly regimen for the first 2 years. In the third year, patients were managed according to routine clinical practice. RESULTS: A total of 18 patients completed the 36 months and were considered for statistical analyses. At 36 months, a nonsignificant decrease of −37.8 μm in central subfield thickness and a nonsignificant gain of 5.8 letters from baseline were observed. CONCLUSION: Despite the significant visual and anatomical gains observed in the 2 years of fixed-dosing IAI, there was gradual decline in these improvements when patients were transitioned to a variable regimen. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:179–185.] more...

Purpose To assess the efficacy of ranibizumab for persistent diabetic macular edema (DME) previously treated with bevacizumab and compare monthly versus treat-and-extend (TREX) dosing. Design Twelve-month open-label prospective, randomized, comparative dosing study. Participants Twenty-seven participants with persistent foveal-involving DME recently treated with bevacizumab. Methods All participants were to receive 3 initial monthly 0.3-mg ranibizumab injections before randomization to monthly (n = 15) or TREX (n = 12) injection protocols over 12 months. The treatment interval was extended by 2 weeks up to a maximum interval of 12 weeks in the TREX group if central subfield thickness (CST) was 300 μm or less or complete absence of intraretinal or subretinal fluid on the macular cube was observed. The follow-up interval was decreased by 2 weeks if CST increased to 300 μm or more with associated intraretinal or subretinal fluid, or both. Main Outcome Measures Change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), CST, and adverse events. Results Before study enrollment, participants received an average of 8.6 bevacizumab injections. At month 12, mean ETDRS BCVA improved by +5.3 letters (P Conclusions After conversion to ranibizumab in eyes with persistent DME refractory to bevacizumab, significant functional and anatomic improvements were noted. Visual and anatomic outcomes were similar in TREX and monthly treatment protocols. more...

BACKGROUND AND OBJECTIVE: Previous literature assessing ocular hemorrhagic complications of anticoagulant/antiplatelet medications in routine clinical practice is limited. This study evaluates the prevalence of spontaneous ocular hemorrhagic events associated with anticoagulation/antiplatelet therapy. PATIENTS AND METHODS: A retrospective study was performed to identify patients taking anticoagulants (rivaroxaban [Xarelto; Janssen Pharmaceuticals, Beerse, Belgium], bivalirudin [Angiomax; The Medicines Company, Parsippany, NJ], lepirudin [Refludan; Bayer HealthCare Pharmaceuticals, Berlin, Germany], dabigatran [Pradaxa; Boehringer Ingelheim, Ingelheim am Rhein, Germany], and argatroban) and antiplatelet agents (clopidogrel [Plavix; Bristol-Myers Squibb, New York City, NY], prasugrel [Effient; Lilly Medical, Indianapolis, IN], and ticagrelor [Brilinta; AstraZeneca, Cambridge, UK]) who presented for an eye examination. Location of hemorrhage, relevant systemic and ocular comorbidities, baseline demographics, and concomitant aspirin use were noted. RESULTS: A total of 44 patients with spontaneous ocular hemorrhage were identified. Thirty patients had a single episode, whereas 14 patients had multiple episodes (two or more hemorrhagic events). Prevalence of spontaneous ocular hemorrhage on prasugrel (7.2%) and rivaroxaban (3.1%) was higher compared to dabigatran (1.9%), clopidogrel (2.0%), and ticagrelor (2.7%). CONCLUSION: Prevalence of spontaneous ocular hemorrhage with use of anticoagulant/antiplatelet agents is higher in routine clinical practice as compared to previously reported literature. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:27–34.] more...

Purpose: To evaluate long-term visual and anatomical outcomes of anti–vascular endothelial growth factor (VEGF) therapy for macular edema (ME) secondary to retinal vein occlusion (RVO) in routine clinical practice. Methods: Patients with ME secondary to hemi-RVO (HRVO), central RVO (CRVO), or branch RVO (BRVO) after initiating anti-VEGF therapy were followed for at least 36 months. Main outcomes were change in best visual acuity (BVA) and mean absolute change in central subfield thickness (CST) at 12, 24, 36, and 48 months. Results: Patients with BRVO showed significant increases in BVA that were maintained after 12, 24, 36, and 48 months (+11.03, +12.06, +10.71, and +9.26 letters, respectively; P < .05). CST significantly decreased after 12, 24, 36, and 48 months (−83.51, −67.93, −97.52, −127.85 µm, respectively; P < .05). In patients with CRVO/HRVO, significant improvements in BVA were seen at 12 and 24 months (+9.39 and +8.54 letters, respectively; P = .023). At 36 and 48 months, the visual gain was not significant (+2.64 and +3.42 letters, respectively; P > .05). For CST changes, there were significant decreases at 12, 24, and 36 months (−146.23, −149.54, and −166.44 µm, respectively; P < .05). At 48 months (−97.66 µm, P = .130), changes in CST were not significant. Conclusions: In routine clinical practice, visual and anatomical benefits of anti-VEGF agents in patients with BRVO were sustained at 36 and 48 months. For patients with CRVO/HRVO, anatomical improvements were maintained for 36, but not 48 months, while visual improvements were no longer maintained by 36 months. more...

BACKGROUND AND OBJECTIVE: To determine outcomes of intravitreal ranibizumab (IVR) (Lucentis; Genentech, South San Francisco, CA) versus bevacizumab (IVB) (Avastin; Genentech, South San Francisco, CA) for treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) in routine clinical practice. PATIENTS AND METHODS: A retrospective study identified treatment-naïve patients with ME secondary to RVO where treatment with either IVB or IVR was initiated. Retreatment criteria were based on ophthalmic examination and/or spectral-domain optical coherence tomography findings. RESULTS: Central RVO/hemi-RVO cohort: At 12 months, change in visual acuity (VA) (IVR: +12.9 letters, IVB +6.9 letters; P = .53), central subfield thickness (CST) (IVR: −144.1 μm, IVB: −153.9 μm; P = .88), and number of injections (IVR: 5.40 injections, IVB: 5.64 injections; P = .70) were not different between groups. Branch RVO cohort: At 12-month follow-up, no differences in change in VA (IVR: +15.2 letters, IVB: +10.6 letters; P = .46), CST (IVR: −23.1 μm, IVB: −91.4 μm; P = .16), or number of injections (IVR: 5.93 injections, IVB: 5.13 injections; P = .15) were noted. CONCLUSION: There is no notable difference in outcome between IVR and IVB when treating ME from RVO in routine clinical practice. [ Ophthalmic Surg Lasers Imaging Retina. 2017;48:465–472.] more...

BACKGROUND AND OBJECTIVE: Evaluate capillary perfusion density (CPD) in patients with diabetic macular edema (DME) undergoing fixed intravit-real aflibercept injections (IAI) through 24 months. PATIENTS AND METHODS: Prospective, interventional, single-arm study enrolling 20 patients with persistent DME. Patients received IAI every 4 weeks until DME resolution followed by extension to every 8 weeks. Optical coherence tomography angiography was obtained at baseline, 6, 12, and 24 months. RESULTS: Sixteen of 20 eyes completed the study. Baseline mean central subfield thickness was 420 µm, which improved to 251 µm ( P < .001). The mean best-corrected visual acuity (BCVA) improved by 5.5 letters ( P = .042). The whole superficial CPD decreased by 5.3% ( P = .001) and the deep CPD decreased by 4.4% ( P = .009). Better BCVA correlated with less CPD loss within the superficial parafovea (r = +0.66 [0.23, 0.88]; P = .006) and whole (r = +0.60 [0.12, 0.85]; P = .017) areas. CONCLUSION: Superficial and deep CPD decreased despite fixed IAI through 24 months. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:448–455.] more...

Purpose On clinical examination, it can be challenging to differentiate retinoschisis with outer retinal hole from schisis-detachment. This study examined the role of outer retinal hole spectral domain optical coherence tomography (SD-OCT) imaging in conjunction with imaging of the posterior schisis cavity edge in differentiating between these conditions. Methods This is a retrospective case series. Out of 500 subjects with ICD-9 diagnoses of senile retinoschisis (361.10, 361.11, 361.12, 361.19) from January 2004 to December 2014, 62 had evidence of retinoschisis on fundus photography or optical coherence tomography (OCT). Six eyes of five patients had outer retinal holes documented by fundus photography (Optos, Marlborough, Massachusetts, USA) and SD-OCT (Carl Zeiss Meditec, Dublin, California, USA). The OCT morphology of outer retinal holes, subjects9 symptomology, visual acuity, fundus examination, diagnosis and progression of the disease were analysed. Results All five patients were women; the mean age was 67.4 years. The correct diagnosis was recorded in the chart in 50% of cases. All, but one, were asymptomatic with visual acuity ranging from 20/20 to 20/200. Three types of outer retinal hole OCT morphology in conjunction with imaging of the posterior schisis cavity edge were established. (1) Outer retinal hole with both edges down and attached to retinal pigment epithelium (RPE) and the edge of the cavity showing a split in neurosensory retina corresponded to isolated retinoschisis. The outer retinal hole with (2) one or (3) both edges detached from the RPE and the edge of the cavity showing complete separation of retina from RPE corresponded to schisis-detachment. One patient underwent scleral buckle surgery for schisis-detachment. Otherwise, no treatment was performed and no progression was noted with the longest OCT-documented follow-up of 26 months. Conclusions The OCT morphology of outer retinal holes in conjunction with imaging of the posterior schisis cavity edge aids in the diagnosis of retinoschisis and schisis-detachment. more...

Background/aimsThe efficacy of mineralocorticoid receptor antagonist eplerenone to treat chronic central serous chorioretinopathy (CSCR) has been established. However, previous studies have been limited by small cohort size and short follow-up duration. This study aims to report 3-year clinical outcomes of patients treated with eplerenone for chronic CSCR.MethodsInstitutional review board-approved retrospective chart analysis at a single institution from 2012 to 2018. Baseline best-corrected visual acuity and anatomical measurements related to degree of subretinal fluid (SRF) were collected at eplerenone initiation. Follow-up data were collected at the closest date to 12, 24 and 36 months.ResultsData were obtained for 100 eyes of 83 patients at 1-year (mean 11.18 ± 4.00 months), 49 eyes at 2-year (24.01 ± 3.33 months) and 33 eyes at 3-year (mean 35.5 ± 7.89 months) follow-up visits. The rate of complete SRF resolution was 31%, 28% and 33%, respectively. At final follow-up, logarithm of the minimum angle of resolution visual acuity change from baseline was +0.10 ± 0.24 (p = 0.130). Average change from baseline at final follow-up for central subfield thickness was −97 ± 140.6 µm (p < 0.001), cube volume was –1.07 ± 1.71 mm3 (p < 0.001), macular thickness –28. 5 ± 47.5 µm (p < 0.001), maximum SRF height was −95.6 ± 160.5 µm (p < 0.001) and maximum SRF diameter was −1169.0 ± 1638.7 µm (p = 0.008).ConclusionAnatomical improvement occurs primarily within the first year of eplerenone treatment for chronic CSCR. more...

Beta-thalassemia (β-thalassemia) minor is characterized by a mutation in one of the two β-globin genes ( HBB ) that produce the β-globin chains in the hemoglobin molecule. Although other hemoglobinopathies have been frequently associated with retinal disease, there are limited reports of retinal pathology with β-thalassemia minor. We report two patients with β-thalassemia minor presenting with decreased vision, vitreous hemorrhage, and proliferative retinopathy. This case report highlights that patients with β-thalassemia minor may require routine ocular examinations for peripheral retinal pathology, and β-thalassemia minor should be considered in the differential diagnosis for proliferative retinopathy. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:e161–e164.] more...

Aim To evaluate efficacy and safety of intravitreal aflibercept injection (IAI) in subjects who were previously treated with ranibizumab and/or bevacizumab for active exudative age-related macular degeneration (AMD). Methods Patients (n=26) were enrolled in a 12-month prospective, interventional, single arm, investigator-initiated study with planned 6-month interim analysis. Patients with active exudative AMD, previously treated with ranibizumab and/or bevacizumab, were treated with 2 mg IAI every month for the first 3 months, followed by a fixed dosing schedule of 2 mg IAI every 2 months. The primary study endpoint was the mean absolute change from baseline central subfield thickness (CST) at month 12 as measured by SDOCT. Secondary outcomes included mean change from baseline best-corrected visual acuity (BCVA) score, percentage of subjects who gained or lost greater than or equal to 15 letters of vision, percentage of subjects who are 20/40 or better, percentage of subjects who are 20/200 or worse, and the incidence of adverse events (AE) and serious AEs. Results Planned 6-month interim analysis demonstrated a mean decrease in CST of 38.6 µm (p more...

Diabetic retinopathy (DR) is one of the leading causes of blindness in the working population worldwide. Vascular leakage, angiogenesis and neuronal degeneration are key features of DR. Current effective interventions for DR include treatment of systemic risk factors such as elevated blood glucose, blood pressure and dyslipidemia. Ocular treatments include vascular endothelial growth factor A (VEGF-A) inhibitors, laser photocoagulation and surgery. While anti-VEGF therapy has become as first-line treatment for diabetic macular edema (DME) that causes reduced vision, intravitreal glucocorticoids also have been shown to be efficacious in this situation. It has been reported that all the major pathological processes of DR are susceptible to glucocorticoid treatment. The effects of glucocorticoids on vascular leakage and angiogenesis may be mediated through their well established anti-inflammatory role. Alternatively, glucocorticoids may affect other mechanisms known to be activated in DR. Potential mechanisms for the anti-inflammatory effects of glucocorticoids include blockage of cytokine production and inhibition of leukocyte adhesion induced by VEGF-A. Glucocorticoids decrease the expression of VEGF-A directly, and increase the production, or decrease phosphorylation, of tight junction-associated proteins. Glucocorticoids have also been shown to be neuroprotective, in contrast to VEGF-A inhibitors which animal studies suggest may be neurotoxic. This review outlines the biological properties of synthetic glucocorticoids, with particular emphasis on the potential beneficial effect of combining glucocorticoids with anti-VEGF treatment for DME and DR. more...

AIM:To compare the efficacy of ranibizumab and bevacizumab for macular edema due to retinal vein occlusion (RVO).METHODS:A retrospective study was conducted at a single academic institution. Eighty-one patients naïve to anti-VEGF therapy with RVO and macular edema were identified. Twenty-six eyes were treated with ranibizumab, 33 eyes with bevacizumab, and 22 eyes with bevacizumab then switched to ranibizumab (crossover). The main outcome was change in visual acuity at 3 months, 6 months, and final visit.RESULTS:The mean visual acuity improved from 20/80 to 20/40 in the ranibizumab (R) group and from 20/125 to 20/60 in the bevacizumab (B) group (P=0.66). The mean change in central subfield thickness (CST) was -186 and -212µm, respectively (P=0.69). Mean time between injections was 94±21.1d in the R group and 103.8±10.5d in the B group (P=0.78). In the crossover group, mean initial visual acuity was 20/125, reached 20/60 at crossover, and remained 20/60 at conclusion (P=0.91).CONCLUSION:Both ranibizumab and bevacizumab are effective for the treatment of RVO and appear to have similar visual and anatomic outcomes. Changing treatments from bevacizumab to ranibizumab did not result in further gains in visual acuity. more...

Rishi P Singh, Sunil K Srivastava, Justis P Ehlers, Fabiana Q Silva, Rumneek Bedi, Andrew P Schachat, Peter K Kaiser Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA Summary statement: In subjects with active exudative age-related macular degeneration, treating with a fixed intravitreal aflibercept injection dosing regimen for 12 months demonstrated improved anatomic and vision endpoints from baseline.Purpose: Switching therapies in neovascular age-related macular degeneration (AMD) may offer an advantage for some patients. This study evaluates the efficacy of intravitreal aflibercept injection (IAI) in subjects previously treated with ranibizumab and/or bevacizumab.Methods: Subjects (n=26) were given monthly 2mg of IAI for 3months, followed by 2mg once in every 2months for up to 12months. The mean absolute change from baseline in central subfield thickness (CST) measured by optical coherence tomography and the mean change from baseline in best-corrected visual acuity (BCVA) early treatment in diabetic retinopathy study (ETDRS) letter score were obtained. Additionally, the percentage of subjects who gained or lost ≥15 letters of vision and the percentage of subjects who are 20/40 or better or 20/200 or worse were evaluated.Results: There was a mean decrease in CST of -50.3 µm (P more...

Aims To compare anti-vascular endothelial growth factor (VEGF) treatment outcomes for macular oedema (ME) secondary to retinal vein occlusion (RVO) based on vitreoretinal interface (VRI) status. Methods This retrospective case series includes treatment-naive eyes diagnosed with RVO and treated with anti-VEGF injections. Eyes were stratified based on international VRI classification schema at baseline into three groups—vitreomacular traction (group A), no posterior vitreous detachment (PVD) (group B) and PVD without vitreomacular attachment (group C). Fifty-two eyes were identified based on inclusion/exclusion criteria. The primary endpoint was change in central subfield thickness (CST) on optical coherence tomography at 6 months. Results There were no statistically significant differences in baseline characteristics of patients with RVO when stratified by VRI subgroups. After 6 months of treatment, there was no statistically significant difference in the change in CST from baseline between VRI cohorts (p=0.11). There was a trend demonstrating the greatest improvement in CST in eyes in group A compared with eyes in groups B and C (−224.13 μm, −160.88 μm and −50.92 μm, respectively, p=0.11 between cohorts). Mean change in logarithm of the minimum angle of resolution visual acuity from baseline to month 6 in group A compared with groups B and C was −0.25, −0.14 and −0.13, respectively (p=0.64 between cohorts). Conclusions We did not identify an association between VRI status and treatment outcomes with anti-VEGF agents for ME secondary to RVO. more...

Background The aim is to compare the therapeutic effects of three antivascular endothelial growth factor (VEGF) drugs (bevacizumab, aflibercept and ranibizumab) on fibrovascular pigment epithelial detachments (fvPEDs) in age-related macular degeneration (AMD). Methods This was a retrospective, comparative, consecutive case series of 88 unique eyes with fvPEDs in neovascular AMD treated with anti-VEGF monotherapy for a minimum of 6 months. All eyes were treatment naive. Diagnosis was confirmed retrospectively by fluorescein angiography and spectral-domain optical coherence tomography. Exclusion criteria included serous/drusenoid PEDs or patients who switched anti-VEGF. Mean follow-up across all therapies was 313.9±85.3 days. Results Average age of all patients was 80.6 years. Baseline maximum subfoveal PED height was 326.8±185.1 μm, 394.5±238.6 μm and 258.0±145.3 μm for bevacizumab, aflibercept and ranibizumab, respectively (p=0.05). All patients had subretinal fluid, intraretinal fluid or a combination of the two at an initial presentation. Central retinal thickness decreased at all time points compared with baseline across all three anti-VEGF therapies. Subfoveal PED height decreased in patients treated with aflibercept at all time points and decreased in patients treated with bevacizumab at 1-month, 3-month and 6-month time points. Aflibercept reduced PED height more than bevacizumab at 1-month and 12-month follow-ups (p=0.02 and p=0.03, respectively) and ranibizumab at 1-month and 6-month follow-ups (p=0.03 and p=0.02, respectively). No differences in best-corrected visual acuity were appreciated at any time point between drugs. Conclusions There was a significant reduction in subfoveal PED height for aflibercept and bevacizumab compared with baseline. A direct comparison of drugs demonstrated a beneficial reduction of PED height, albeit inconsistently, favouring aflibercept. There were no differences in visual acuity across the groups at any time point. more...

To compare retinal layer volumes using spectral-domain optical coherence tomography between eyes with hydroxychloroquine (HCQ) toxicity and control eyes.Using a previously validated algorithm, volumetric analysis from the macular cube scan of the ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer retina (outer plexiform layer to retinal pigment epithelium) layers were compared in three sets of patients: patients with a clinical diagnosis of HCQ toxicity, age-matched patients taking HCQ but not manifesting overt toxicity, and age-matched control patients.There were 14 patients in each group. The ganglion cell layer (P = 0.01), inner plexiform layer (P = 0.004), inner nuclear layer (P0.001), and outer plexiform layer to retinal pigment epithelium (P0.001) volumes were significantly reduced in HCQ toxicity eyes relative to the HCQ exposure eyes. There were no significant inner and outer retinal volume differences between the HCQ exposure group and group with no HCQ use (P0.05 for all layers). Increasing disease severity correlated with increasing volume loss in the inner retina (2.27 mm in early disease vs. 1.78 mm in advanced retinopathy, P = 0.02).Hydroxychloroquine toxicity seems to result in both outer and inner retinal volumetric thinning compared with age-matched control patients and patients taking HCQ but not manifesting toxicity. more...

Purpose To report new findings revealed by spectral-domain optical coherence tomography in a patient with bilateral acute retinal pigment epitheliitis. Methods A patient presented with bilateral central scotoma and clinical and angiographic findings consistent with acute retinal pigment epitheliitis. Spectral-domain optical coherence tomography was performed at presentation and throughout follow-up. Results Early spectral-domain optical coherence tomography showed hyperreflectivity throughout the full thickness of the foveola, suggesting a full-thickness foveal inflammatory disorder. Later images provide insight into the natural course of acute retinal pigment epitheliitis and eventually showed a small outer retinal defect similar to that reported in some patients with macular microhole or foveal red spot. Conclusion Acute retinal pigment epitheliitis is a macular inflammatory disorder that can involve the full thickness of the fovea and underlying retinal pigment epithelium and may result in a small defect in the outer retina similar to that reported in some patients with macular microhole or foveal red spot. more...

To determine the impact of initial visual acuity (VA) on anti-vascular endothelial growth factor (VEGF) treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice.A retrospective study was conducted at a single academic institution to identify 177 treatment naïve patients with macular oedema secondary to branch retinal vein occlusion (BRVO), hemiretinal vein occlusion (HRVO) and central retinal vein occlusion (CRVO) treated with intravitreal anti-VEGFs. Exclusion criteria included prior intravitreal injection or presence of active confounding ocular disease. Patients were stratified by initial VA; main outcomes measured were average change in VA and mean absolute change in central subfield thickness (CST) at 6 and 12 months.Patients with BRVO with initial VA of 20/40 or better had no significant changes in average letters gained and CST from baseline (+2.6 letters, p=0.42; -48.94 µm, p=0.12) compared with patients with initial VA between 20/50 and 20/300 (+13.2 letters, p0.001; -98.20 µm, p0.001) after 12 months. Patients with CRVO/HRVO with initial VA of 20/320 or worse had the most improvement in average letters gained and CST from baseline (+42.2 letters, p0.001; -182.84 µm, p=0.004) with anti-VEGF therapy compared with patients with initial VA between 20/50 and 20/300 (+9.4 letters, p=0.016; -160.87 µm, p0.001) and patients with initial VA of 20/40 or better (-9.6 letters, p=0.14; -47.92 µm, p=0.38).For macular oedema secondary to retinal vein occlusion, anti-VEGF treatment can result in a greater improvement in average letters gained and in CST for those with poor initial VA compared with those with better initial VA. more...

Non-contiguous local recurrence of posterior uveal melanoma occurs rarely after plaque therapy. A 50-year-old white first presented with choroidal melanoma. He underwent therapy with episcleral iodine-125 radioactive plaque therapy. Nine years later fundus evaluation revealed a new pigmented lesion in the inferotemporal equatorial area. Patient was considered to have a non-contiguous recurrent melanoma and the eye was enucleated. Histologic microscopic examination disclosed a 3 x 1.8 mm densely pigmented tumour internal to the choroid at the equator. The tumour was composed of large round cells with round nuclei, prominent nucleoli, abundant cytoplasm and spindle-shaped cells with spindle-shaped nuclei and prominent nucleoli. The tumour extended through the retina. The superior nasal area of plaque therapy had extensive chorioretinal atrophy with loss of retinal pigment epithelium, thinning of the retina and thinning and depigmentation of the choroids. Within this area of atrophy, there was a pigmented lesion composed by densely packed, spindle-shaped cells with spindle-shaped nuclei. Our patient illustrated non-contiguous recurrence of choroidal melanoma, such finding raises concerns about physiopathology and treatment of choroidal melanoma. more...

Age-related macular degeneration is one of the most common irreversible causes of visual loss. It has been well established from both animal and human studies that vascular endothelial growth factor plays an important role in the pathogenesis of this process. Ranibizumab is a monoclonal antibody fragment directed towards human vascular endothelial growth factor that was developed to halt the progression of wet age-related macular degeneration. The antibody fragment has a molecular weight of 48 kDa and is produced by an Escherichia coli expression system. Ranibizumab received approval in the USA in July 2006 and the European Union in January 2007. It is introduced into the eye by injection into the vitreous cavity. Conjunctival hemorrhage, vitreous floaters, intraocular inflammation, increased intraocular pressure and eye pain were the most common ocular complaints of patients receiving ranibizumab injections over sham treatments. The rates of retinal detachment, cataract and endophthalmitis do not exceed that of other intravitreal injections and patients should be treated under strict aseptic conditions to reduce this risk. No unanticipated systemic adverse events were found during any phase of the studies of ranibizumab thus far and the risk of thromboembolic events was less than 4% and not different to sham. Combined data from the Minimally classic/occult trial of the Anti-vascular endothelial growth factor antibody Ranibizumab In the treatment of Neovascular Age-related macular degeneration (MARINA), ANti-vascular endothelial growth factor antibody for the treatment of predominantly classic CHORoidal neovascularization in age-related macular degeneration (ANCHOR), and Phase IIIb, multicenter, randomized, double-masked, sham Injection-controlled study of the Efficacy and safety of Ranibizumab in subjects with subfoveal choroidal neovasularization with or without classic choroidal neovascularization secondary to age-related macular degeneration (PIER) studies have validated the safety and efficacy of ranibizumab amongst a large population compared with sham and standard treatment (photodynamic therapy). Intravitreal administration is recommended monthly for patients. However, an alternative dosing of every 3 months is better than no treatment but probably less effective than sham treatment. more...

The Diabetic Retinopathy Clinical Research Network (DRCR Network), sponsored by the National Eye Institute, reported the results of a comparative effectiveness randomized clinical trial (RCT) evaluating the 3 anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept (2.0 mg), bevacizumab (1.25 mg), and ranibizumab (0.3 mg) for treatment of diabetic macular edema (DME) involving the center of the retina and associated with visual acuity loss. The many important findings of the RCT prompted the American Society of Retina Specialists to convene a group of experts to provide their perspective regarding clinically relevant findings of the study.To describe specific outcomes of the RCT judged worthy of highlighting, to discuss how these and other clinically relevant results should be considered by specialists treating DME, and to identify unanswered questions that merit consideration before treatment.The DRCR Network-authored publication on primary outcomes of the comparative effectiveness RCT at 89 sites in the United States. The study period of the RCT was August 22, 2012, to August 28, 2013.On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and with visual acuity impairment, including mean (SD) improvements by +13.3 (11.1) letters with aflibercept vs +9.7 (10.1) letters with bevacizumab (P.001) and +11.2 (9.4) letters with ranibizumab (P = .03). Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept (+18.9 [11.5]) over bevacizumab (+11.8 [12.0]) or ranibizumab (14.2 [10.6]) 1 year later (P.001 for interaction with visual acuity as a continuous variable, and P = .002 for interaction with visual acuity as a categorical variable). It is unknown whether different visual acuity outcomes associated with the use of the 3 anti-VEGF agents would be noted with other treatment regimens or with adequately repackaged bevacizumab, as well as in patients with criteria that excluded them from the RCT, such as persistent DME despite recent anti-VEGF treatment.On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and visual acuity impairment. Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept over bevacizumab or ranibizumab 1 year later. Care needs to be taken when attempting to extrapolate outcomes of this RCT to differing treatment regimens. With access to adequately repackaged bevacizumab, many specialists might initiate therapy with bevacizumab when visual acuity is good (ie, 20/32 to 20/40 as measured in the DRCR Network), recognizing that the cost-effectiveness of bevacizumab outweighs that of aflibercept or ranibizumab. more...

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in individuals over the age of 50 years. Choroidal neovascularization (CNV) is the hallmark of 'wet' or 'exudative' AMD, and is responsible for approximately 90% of cases of severe vision loss due to AMD. Vascular endothelial growth factor (VEGF) is a key component in the development and progression of wet AMD. Since the approval of ranibizumab in 2006, VEGF inhibitors have rapidly altered the treatment and standard of care for wet AMD. Ranibizumab, bevacizumab, and aflibercept are now the most widely used anti-VEGF agents for the treatment of wet AMD. This chapter discusses the pharmacologic properties, pharmacokinetics, safety, and efficacy of these medications, as well as revisits landmark clinical trials that establish these drugs as gold standards in care. While these medications have greatly and positively altered the way we treat AMD, there are still many economic and therapeutic limitations with our current therapy regimens. There continue to be advancements and innovations in exploring alternative and new treatment modalities, as well as combining existing treatment options to improve efficacy, and reduce cost and patient burden. more...

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in individuals over the age of 50 years. Choroidal neovascularization (CNV) is the hallmark of 'wet' or 'exudative' AMD, and is responsible for approximately 90% of cases of severe vision loss due to AMD. Vascular endothelial growth factor (VEGF) is a key component in the development and progression of wet AMD. Since the approval of ranibizumab in 2006, VEGF inhibitors have rapidly altered the treatment and standard of care for wet AMD. Ranibizumab, bevacizumab, and aflibercept are now the most widely used anti-VEGF agents for the treatment of wet AMD. This chapter discusses the pharmacologic properties, pharmacokinetics, safety, and efficacy of these medications, as well as revisits landmark clinical trials that establish these drugs as gold standards in care. While these medications have greatly and positively altered the way we treat AMD, there are still many economic and therapeutic limitations with our current therapy regimens. There continue to be advancements and innovations in exploring alternative and new treatment modalities, as well as combining existing treatment options to improve efficacy, and reduce cost and patient burden. more...

PurposeTo assess of the effect of local recurrence of uveal melanoma on metastasis using a multicenter international tumor registry.DesignRetrospective study using an online tumor registry.ParticipantsPatients with uveal melanoma diagnosed between 2001 and 2011.MethodsA committee was formed to create uveal melanoma patient-specific data fields. Ten subspecialty ophthalmic oncology centers from 4 continents shared data. Patient selection criteria included diagnosis of uveal melanoma and adequate records to allow tumor staging by American Joint Committee on Cancer (AJCC) criteria and follow-up for metastatic melanoma.Main Outcome MeasuresLocal tumor recurrence and metastatic uveal melanoma.ResultsOf 3809 total entries, 3217 patients with ciliary body and choroidal (CBC) melanoma and 160 with iris melanoma were evaluated. There was a median follow-up of 3.7 years (95% confidence interval [CI], 3.5–3.8). One hundred fifty-two patients (4.7%) with CBC melanoma experienced local recurrence, with a cumulative incidence of 11%. Kaplan-Meier point estimates for remaining free of local recurrence were 99% (95% CI, 99–99) at 1 year, 93% (95% CI, 92–94) at 5 years, and 89% (95% CI, 86–91) at 10 years. Five- and 10-year metastasis-free Kaplan-Meier estimates for the recurrence-free group were 87% (95% CI, 86–89) and 82% (95% CI, 79–84), and those for the local recurrence group were 71% (95% CI, 62–78) and 62% (95% CI, 49–72). The difference between these 2 groups was statistically significant (P < 0.001). Furthermore, local tumor recurrence increased the risk of metastasis by a hazard ratio (HR) of 6.28 (95% CI, 4.4–8.9; P < 0.001). Local recurrence was detected up to 9.8 years after treatment. Extrascleral extension also was associated with local recurrence (HR, 3.2; 95% CI, 1.5–6.7; P = 0.003), but higher AJCC T-size category was not (P = 0.63). Five patients (n = 5/161 [3.1%]) with iris melanoma demonstrated local recurrence and 1 metastasized.ConclusionsInternational multicenter data sharing was used to evaluate the effect of local tumor recurrence on metastatic rate. In that local tumor recurrence was associated with a significantly higher risk of systemic metastasis, effective initial treatment and long-term surveillance of treated uveal melanoma patients is necessary. more...

Although an accurate uveal melanoma staging system is needed to improve research and patient care, the evaluation of eye cancer staging systems requires international multicenter data sharing to acquire a statistically significant analysis.To assess patient mortality outcomes associated with uveal melanoma staging according to the 7th edition of the American Joint Committee on Cancer's AJCC Cancer Staging Manual.A committee was formed to create patient-specific data fields for patients with uveal melanoma. Ten subspecialty ophthalmic oncology centers from 4 continents shared data. Patient selection criteria included diagnosis of uveal melanoma from April 1, 2001, to April 1, 2011, adequate records to allow tumor staging by the AJCC criteria, and follow-up for metastatic melanoma.Primary treatments included local resection, radiation therapy, and enucleation.Metastasis after initial tumor staging with 5- and 10-year Kaplan-Meier metastasis-free point estimates, depending on AJCC prognostic stages I through IV, tumor size category, and subclassification (defined by the presence of ciliary body involvement and/or extrascleral extension).A total of 3809 patients were entered into the database. Of these, 3377 records (88.7%) were complete. Primary ciliary body and choroidal melanoma was the diagnosis for 3217, and 160 had primary iris melanoma. Tumor size categories were T1 in 1115 (34.7%) of the 3217 patients, T2 in 1128 patients (35.1%), T3 in 789 patients (24.5%), and T4 in 185 patients (5.8%). The 5- and 10-year Kaplan-Meier metastasis-free point estimates by tumor size categories were 97% (95% CI, 95%-98%) and 94% (95% CI, 91%-96%) for T1 tumors, 85% (95% CI, 82%-88%) and 80% (95% CI, 75%-84%) for T2 tumors, 77% (95% CI, 73%-80%) and 68% (95% CI, 60%-74%) for T3 tumors, and 61% (95% CI, 49%-71%) (5-year only) for T4 tumors, respectively. Increasing tumor size was consistent with increased metastasis risk (P .001). Subclassifications were significantly associated with increased risk of metastasis (P.001). The AJCC prognostic and anatomical groupings were as follows: stage I, 1030 (32.0%); stage IIA, 1095 (34.0%); stage IIB, 710 (22.1%); stage IIIA, 282 (8.8%); stage IIIB, 79 (2.5%); and stage IIIC, 21 (0.7%). The 5- and 10-year Kaplan-Meier metastasis-free estimates for prognostic stages were 97% (95% CI, 95%-98%) and 94% (95% CI, 91%-96%) for stage I, 89% (95% CI, 86%-91%) and 84% (95% CI, 80%-88%) for stage IIA, 79% (95% CI, 75%-83%) and 70% (95% CI, 62%-76%) for stage IIB, 67% (95% CI, 59%-73%) and 60% (95% CI, 51%-68%) for stage IIIA, 50% (95% CI, 33%-65%) and 50% (95% CI, 33%-65%) for stage IIIB, and 25% (95% CI, 4%-53%) (5-year only) for stage IIIC, respectively. The 160 iris melanomas were too few for subgroup analysis.Multicenter, worldwide, Internet-based data sharing was used to study a heterogenous patient population in ophthalmic oncology. Our results support the continued use of the 7th edition of the AJCCCancer Staging Manual for uveal melanoma. more...

Purpose To determine provider compliance with hydroxychloroquine screening following the revised recommendations published in 2011 by the American Academy of Ophthalmology. Design Evaluation of adherence to a screening protocol. Methods Subjects were identified with hydroxychloroquine as a medication by electronic query at a large multispecialty ophthalmic practice. Patients were excluded if patients: (1) were screened by an outside physician; (2) lacked recorded height, weight, start date, or dosing; or (3) took hydroxychloroquine for malaria prophylaxis. Screening tests were stratified by ophthalmic subspecialty. Guidelines define proper screening as 1 subjective test—Humphrey visual field (HVF), and 1 objective test—spectral-domain optical coherence tomography (SD OCT), fundus autofluorescence (FAF), or multifocal electroretinography (mfERG). Adherence to guidelines was determined by categorizing practices as: (1) “appropriate”—consistent with guidelines; (2) “underscreened”—insufficient testing; or (3) “inappropriate”—no testing. Results The study comprised 756 patients with a mean age of 56 years undergoing 1294 screening visits. Twenty-one patients received initial screenings outside the institution. Most common screening tests employed included SD OCT (56.6%), 10-2 HVF (55.0%), and Amsler grid (40.0%). Of the 735 initial screenings, 341 (46.4%) were appropriately screened, 204 (27.8%) underscreened, and 190 (25.9%) inappropriately screened. Of those who presented solely for screening (560), 307 (54.8%) were appropriately screened, 144 (25.7%) underscreened, and 109 (19.5%) inappropriately screened. Conclusions Of patients presenting for hydroxychloroquine screening, 54.8% of patients received appropriate evaluation, indicating lack of adherence to guidelines. Overall, SD OCT and 10-2 HVF were the preferred screening modalities, with FAF and mfERG less frequently ordered. more...

To provide 9-year incidence estimates of age-related macular degeneration (AMD) in a population of African descent.Population-based cohort study.Two thousand seven hundred ninety-three participants (81% of eligible) after 9 years' follow-up.Nine-year incidence of AMD-related features, based on fundus photographic gradings and/or clinical examinations.The overall incidence rate of early AMD was 12.6% (95% confidence interval [CI], 11.0%-14.1%), and that of late AMD was 0.7% (95% CI, 0.4%-1.1%). Both increased with age (P0.05). For early AMD, incidence ranged from 10.7% at 40 to 49 years of age to 16.8% ator =70 years. For late AMD, incidence increased from 0.1% to 2.3% in the same age groups. Late AMD was more likely to develop in eyes with pigment changes (risk ratio [RR], 5.8; 95% CI, 2.0-16.8) and retinal pigment epithelial atrophy (RR, 5.4; 95% CI, 1.9-15.8) at baseline. Crude RRs indicated significant associations of late AMD to elevated systolic blood pressure and diabetes history, but only the diabetes relationship was suggested after adjusting for age, with borderline statistical significance (age-adjusted RR, 2.7; P = 0.054).Nine-year data on natural history indicate that early AMD is common in this population of African origin, although late AMD is infrequent. These long-term observations provide further evidence for the lower AMD risk in black populations compared with white populations. more...

Several recent developments may provide an opportunity to improve outcome in individuals who develop neovascular age-related maculopathy (age-related macular degeneration [ARMD]). Concurrent with progress in isolating clinically relevant subtypes of neovascular ARMD, several therapies have been introduced that show promise for halting progression of this disorder. However, data from controlled clinical trials to test the relative efficacy of different management strategies across these subtypes of disease presentation remain limited. In addition, strategies to control ARMD may evolve quickly as more is learned about how specific molecular events, such as cell-mediated inflammation and angiogenesis, contribute to disease expression. A roundtable of investigators was convened to discuss and summarize recent progress in the treatment of ARMD. Case studies were then presented to provide an opportunity for experts to reveal their specific thought processes in the approach to neovascular ARMD based on their own interpretation of current clinical data and empirical experience. more...