URINARY METABOLOMICS OF CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To analyze the urinary metabolomic profile of central serous chorioretinopathy cases. METHODS: In a cross-sectional study, 80 participants with central serous chorioretinopathy were compared with 80 age-matched and sex-matched controls. Urinary metabolites were measured using Metabolon's Discovery HD4 platform. RESULTS: Of 1,031 metabolites total that were measured in urine samples, 53 were upregulated and 27 downregulated in central serous chorioretinopathy participants compared with controls. After exclusion of potentially confounding xenobiotics and bile compounds that could represent digestive processes, 14 metabolites were significantly higher and 12 metabolites were significantly lower in cases compared with controls. One upregulated metabolite (tetrahydrocortisol sulfate) is involved in the corticosteroid subpathway. The downregulated metabolites are unrelated to the identified corticosteroid subpathway. CONCLUSION: The upregulation of urinary tetrahydrocortisol sulfate in central serous chorioretinopathy cases provides a precise molecular basis to further study the role of corticosteroids in producing choroidal venous congestion.

Patient Use of Dietary Supplements, Home Monitoring, or Genetic Testing for Nonneovascular Age-Related Macular Degeneration.

Purpose: This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD. Methods: A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants' use of genetic testing for AMD. Results: Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring. Conclusions: Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.

Survey of Ehlers-Danlos Patients' ophthalmic surgery experiences.

BACKGROUND: Ehlers-Danlos Syndrome (EDS) is a rare disease affecting approximately 1 in 5,000 people. Although ophthalmic conditions associated with EDS have been described, little data exist concerning ophthalmic surgical outcomes experienced by EDS patients. METHODS: Patients with EDS were surveyed via the EDS Society and asked about their ophthalmic surgical experiences including procedure, complications, and the timing with respect to receiving the EDS diagnosis. Complications were confirmed as such by subspecialists. RESULTS: Of 579 respondents, 467 reported confirmed EDS, and 112 of those had an ophthalmic procedure, including refractive surgery, cataract/lens surgery, retinal surgery, strabismus surgery, oculoplastic surgery, corneal surgery, and laser surgery for glaucoma. The rate of confirmed complications was: 23%-refractive, 33%-lens/cataract, 33%-retina, 59%-strabismus, 23%- oculoplastics, 0%-cornea, and 25%-glaucoma laser. In addition, 76% of patients underwent surgery prior to the EDS diagnosis. CONCLUSIONS: Patients with EDS may have elevated risk of postoperative ophthalmic surgical complications. It would seem reasonable to systemically and prospectively explore how patients with EDS respond to ophthalmic surgery. Furthermore, it would seem circumspect to ask surgical candidates patients about whether they carry a diagnosis of EDS or have signs and symptoms of EDS prior to surgery.

Evaluation of Choroidal Layer Thickness in Central Serous Chorioretinopathy.

PURPOSE: To evaluate medium and large choroidal vessel layer thickness (MCVT and LCVT, respectively) in eyes with acute and chronic central serous chorioretinopathy (CSC) in comparison with age-matched controls. METHODS: The study included 96 eyes of 96 patients with CSC, including 53 eyes with acute CSC, 43 eyes with chronic CSC, and 30 eyes of 30 age-matched normal subjects. Manual measurements of subfoveal choroidal thickness (SFCT), MCVT, and LCVT at subfoveal and 750 µm nasal and temporal to the fovea locations were made on enhanced depth imaging optical coherence tomography (EDI-OCT) of the macula in all subjects using ImageJ software (National Institutes of Health, Bethesda, MD, USA). RESULTS: SFCT in acute CSC was significantly larger than that in healthy eyes (P = 0.0001). SFCT in acute CSC did not differ significantly from that in chronic CSC eyes. Subfoveal LCVT and MCVT in acute CSC eyes were greater than those in healthy eyes (P = 0.02 and P = 0.03, respectively). Mean SFCT and MCVT in chronic CSC eyes were significantly larger than those in control eyes (P = 0.01 and P = 0.04, respectively). No significant difference in LCVT was observed between chronic and control eyes. CONCLUSION: Choroidal vasculature is altered in both acute and chronic CSC. SFCT, MCVT, and LCVT are higher in eyes with acute CSC. The thickening of medium choroidal vessels is still detectable in chronic CSC compared to control eyes.

Loss of Peak Vision in Retinal Vein Occlusion Patients Treated for Macular Edema.

PURPOSE: To evaluate long-term visual and anatomic outcomes in patients with retinal vein occlusion (RVO) treated with anti-vascular endothelial growth factor (VEGF) agents. DESIGN: Prospective, interventional case series. PARTICIPANTS: Patients with central RVO (CRVO) or branch RVO (BRVO). METHODS: Number of anti-VEGF injections and improvement from baseline best-corrected visual acuity (BCVA) and central subfield thickness (CST) were prospectively recorded in 40 eyes of 39 CRVO patients and 50 eyes of 47 BRVO patients. RESULTS: Mean follow-up was 58 months for BRVO and 78 months for CRVO. Within 6 months of last follow-up, 58% of BRVO patients and 75% of CRVO patients required anti-VEGF injections to control edema. Analysis of the course of each patient over time showed that for BRVO patients, BCVA letter score increased by a mean of 24, from baseline of 52 (20/100) to peak of 76 (20/32), and subsequently decreased by 13, to 63 (20/50), at final visit; and for CRVO patients, BCVA letter score increased by a mean of 26, from baseline of 48 (20/100) to peak of 74 (20/32), and subsequently decreased by 18, to 56 (20/80), at last follow-up. Loss from peak BCVA occurred primarily owing to persistent/recurrent edema and related foveal damage. CONCLUSIONS: Patients with RVO showed large improvements in BCVA after initiation of anti-VEGF injections, but in many patients some visual gains were lost over time owing to bouts of recurrent edema. Sustained suppression of VEGF may help to provide optimal outcomes in RVO and reduce treatment burden.

Gender variation in central serous chorioretinopathy.

BACKGROUND: Comparison of presentation and outcomes of central serous chorioretinopathy (CSC) between male and female subjects in different ethnic populations. METHODS: Retrospective comparison between male and female subjects with CSC was completed. Demographic details, clinical presentations, imaging features and treatment outcomes were compared at baseline and at last follow-up. RESULTS: This study included 155 male and 155 female subjects with a mean (CSD) age of 43.8 ± 10.3 and 57.0 ± 12.1 years, respectively, and a mean duration of follow-up of 8.49 ± 12.6 months. At presentation, there was no difference in visual acuity; however, visual acuity was significantly higher for female subjects at last follow-up (p = 0.02). Optical coherence tomography (OCT) analysis showed that subretinal deposits (p < 0.001), hyperreflective foci (p = 0.001), retinal pigment epithelial detachment (p = 0.01) and retinal pigment epithelium (RPE) irregularities (p = 0.03) were higher in male subjects at presentation. Angiographic analysis showed that diffuse leakage and RPE tracts were common in males (p = 0.01 and p = 0.02). No significant differences in choroidal dilatation or diffuse choroidal leakages were noted. CONCLUSIONS: Female subjects with CSC appear to have better outcomes, with less chances of diffuse RPE damage and other OCT features compared to males.

Central Serous Chorioretinopathy in African Americans at Wilmer Eye Institute.

OBJECTIVE: To evaluate the frequency of central serous chorioretinopathy (CSC) in African Americans/blacks within an academic center in a predominantly African American city, as the current belief is that CSC is rare in this population. METHODS: A retrospective review of all patients' charts diagnosed with CSC at Wilmer Eye Institute/Johns Hopkins University from August 2009-August 2015 was conducted via an electronic health record search (EPIC). The charts were categorized by self-reported race and gender. The diagnosis was confirmed by multiple physician consensus through chart and imaging review. Fluorescein angiograms were classified as single versus multiple point leakage. OCTs were evaluated for subfoveal thickness, location of fluid, presence or absence of pigment epithelial detachment. Color photos were categorized as to the extent of retinal pigment epithelial changes. RESULTS: Of the 590 charts identified via EPIC as CSC patients, 407 were confirmed as CSC through chart and imaging review. 45 patients (11.1%) were African Americans and 298 patients (73.2%) were Caucasians. Of all patients seen during the study period, 0.09% of African Americans at Wilmer had CSC and 0.18% of Caucasians had CSC. While three fold more Caucasians were seen during the study period as compared to African Americans, this study's prevalence rate in African Americans/blacks at Wilmer Eye Institute was half of that in Caucasian/whites. CONCLUSIONS: CSC has been reported as exceedingly rare in African Americans, but our study suggests that CSC may be underestimated in this population. A large nationally representative population based study is needed to determine true racial prevalence to ensure that the diagnosis of CSC is not overlooked in African Americans.

Shortest Distance From Fovea to Subfoveal Hemorrhage Border Is Important in Patients With Neovascular Age-related Macular Degeneration.

PURPOSE: To identify factors influencing visual outcome in patients with neovascular age-related macular degeneration (NVAMD) and subfoveal hemorrhage (SFH) treated with anti-vascular endothelial growth factor (VEGF) agents. DESIGN: Retrospective case series. METHODS: Anti-VEGF-treated eyes with SFH > 1 disc area (DA) were identified (n = 16) and changes in visual acuity (VA) and central subfield thickness (CST) from baseline to last follow-up, along with SFH area, thickness, minimum distance from fovea to SFH border, and time to resolution, were determined. RESULTS: At baseline, mean (± standard error of the mean) size and thickness of SFH were 14.9 ± 2.8 DA and 386.6 ± 46.9 µm, and mean Snellen VA and CST were 20/250 and 591.7 ± 57.0 µm. Median follow-up was 47.6 months. While more than 50% of patients had VA ≤ 20/200 at baseline and all time points through week 48, the percentage of patients with VA ≥ 20/50 increased to 30%-40% at months 6 and 12 and remained stable through month 48. Spearman rank correlation demonstrated 2 independent variables that correlated with good visual outcome, smaller area of SFH at baseline (r = -0.630; P = .009), and high frequency of anti-VEGF injections (r = 0.646; P = .007). In exceptional patients with good visual outcome despite large baseline SFH, shortest distance between the fovea and hemorrhage border significantly correlated with baseline VA (r = -0.503, P = .047) and final VA (r = -0.575, P = .02). CONCLUSIONS: Patients with NVAMD and thick SFH, but short distance between fovea and uninvolved retina, can have good visual outcomes when given frequent anti-VEGF injections.

Comparison of Clinical Trial and Systematic Review Outcomes for the 4 Most Prevalent Eye Diseases.

Importance: Suboptimal overlap in outcomes reported in clinical trials and systematic reviews compromises efforts to compare and summarize results across these studies. Objectives: To examine the most frequent outcomes used in trials and reviews of the 4 most prevalent eye diseases (age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], and glaucoma) and the overlap between outcomes in the reviews and the trials included in the reviews. Design, Setting, and Participants: This cross-sectional study examined all Cochrane reviews that addressed AMD, cataract, DR, and glaucoma; were published as of July 20, 2016; and included at least 1 trial and the trials included in the reviews. For each disease, a pair of clinical experts independently classified all outcomes and resolved discrepancies. Outcomes (outcome domains) were then compared separately for each disease. Main Outcomes and Measures: Proportion of review outcomes also reported in trials and vice versa. Results: This study included 56 reviews that comprised 414 trials. Although the median number of outcomes per trial and per review was the same (n = 5) for each disease, the trials included a greater number of outcomes overall than did the reviews, ranging from 2.9 times greater (89 vs 30 outcomes for glaucoma) to 4.9 times greater (107 vs 22 outcomes for AMD). Most review outcomes, ranging from 14 of 19 outcomes (73.7%) (for DR) to 27 of 29 outcomes (93.1%) (for cataract), were also reported in the trials. For trial outcomes, however, the proportion also named in reviews was low, ranging from 19 of 107 outcomes (17.8%) (for AMD) to 24 of 89 outcomes (27.0%) (for glaucoma). Only 1 outcome (visual acuity) was consistently reported in greater than half the trials and greater than half the reviews. Conclusions and Relevance: Although most review outcomes were reported in the trials, most trial outcomes were not reported in the reviews. The current analysis focused on outcome domains, which might underestimate the problem of inconsistent outcomes. Other important elements of an outcome (ie, specific measurement, specific metric, method of aggregation, and time points) might have differed even though the domains overlapped. Inconsistency in trial outcomes may impede research synthesis and indicates the need for disease-specific core outcome sets in ophthalmology.

Systemic Sunitinib Malate Treatment for Advanced Juxtapapillary Retinal Hemangioblastomas Associated with von Hippel-Lindau Disease.

PURPOSE: To describe the clinical course of advanced juxtapapillary retinal capillary hemangioblastomas (RCH) associated with von Hippel-Lindau (VHL) disease treated with systemic sunitinib malate, an agent that inhibits both anti-vascular endothelial growth factor and anti-platelet-derived growth factor signaling. DESIGN: Observational case review. PARTICIPANTS: Three patients with advanced VHL-related juxtapapillary RCH treated with systemic sunitinib malate. METHODS: Patient 1 was followed routinely every 4 months while on systemic sunitinib prescribed by her oncologist for metastatic pancreatic neuroendocrine and kidney tumors. Patients 2 and 3 were part of a prospective clinical trial evaluating the use of systemic sunitinib for ocular VHL lesions during a period of 9 months. Visual acuity, size of RCH, and degree of exudation were recorded at each visit. Optical coherence tomography (OCT) and fluorescein angiography were also obtained at some visits. MAIN OUTCOME MEASURES: Visual acuity, size of RCH, and degree of exudation. RESULTS: Three patients with advanced VHL-associated juxtapapillary RCH were treated with systemic sunitinib malate. While none of the patients lost vision during therapy, treatment with sunitinib malate did not improve visual acuity or reduce the size of RCH. Improvements in RCH-associated retinal edema were observed in two patients. All patients experienced multiple adverse effects, including thyroid toxicity, thrombocytopenia, nausea, fatigue, jaundice, and muscle aches. Two of the three patients had to discontinue treatment prematurely and the third required dose reduction. CONCLUSIONS: Systemic sunitinib malate may be useful in slowing progression of ocular disease from VHL-associated RCH. However, significant systemic adverse effects limited its use in this small series, and systemic sunitinib malate may not be safe for treatment of RCH when used at the doses described in this report. Further studies are required to determine if this medication used at lower doses with different treatment strategies, other medications in the same class or drugs directed at multiple targets in the tumor, may be safer and more effective for the treatment of advanced VHL-associated RCH.

Evolution of Geographic Atrophy in Participants Treated with Ranibizumab for Neovascular Age-related Macular Degeneration.

PURPOSE: To evaluate the risk factors, incidence, and rate of progression of geographic atrophy (GA) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab. DESIGN: Post-hoc analysis of a prospective clinical study. PARTICIPANTS: 69 participants with nAMD in at least one eye. METHODS: Participants were prospectively treated in the study eye with 0.5 mg intravitreal ranibizumab. Study eyes received 4 monthly injections followed by pro re nata injections until a fluid-free macula was achieved on optical coherence tomography. Risk factors assessed included baseline demographics, treatment, and ocular characteristics on imaging. Eyes were evaluated on fundus autofluorescence (FAF) for GA. The rate of GA area growth in study and fellow eyes was analyzed by linear regression of square-root transformed areas. MAIN OUTCOME MEASURES: Development of new-onset GA and rate of GA area growth measured on ocular imaging, including FAF images of the study eyes. RESULTS: Sixty-nine participants (mean age 78.8±7.8 years) with an average of 40.0±13.6 months of follow-up were analyzed. Twenty-two of 69 study eyes (32%) were treatment naïve. During their first year of the study, participants received an average of 9.2±3.3 injections in the study eye. Of 63 study eyes with quality baseline images, 22 (35%) had pre-existing GA. Of the remaining 41 eyes, 7 (17%) developed new-onset GA during study follow-up. Those who developed new GA were older (all ≥79 years old) and had received fewer study injections on average (6.9 vs. 10.4 injections at 1 year) compared to those who did not develop new GA. Of the 12 treatment naïve study eyes without GA at baseline, 1 (8.3%) developed new GA during the study. In 21 study eyes with quantifiable GA area, eyes with GA present at baseline (16/21) enlarged by 0.34±0.26 mm/year, compared to 0.19±0.12 mm/year in eyes developing new-onset GA (5/21). CONCLUSIONS: While 17% of study eyes without GA present at baseline receiving ranibizumab developed new GA, the role of ranibizumab in the development of GA is unclear. Further prospective longitudinal studies are required to determine the eyes most at risk of developing GA in the setting of anti-VEGF treatment.

Age-related macular degeneration in patients with uveitis.

PURPOSE: To evaluate the prevalence of large drusen in a uveitis clinic population. DESIGN: Retrospective, cohort study. METHODS: Patients with primary, non-infectious uveitis 55 years or older who were seen at the National Eye Institute of the National Institutes of Health from 2004 through August 2013 were reviewed using electronic medical records and photographic databases. Patients were classified as having age-related macular degeneration (AMD) if either eye had large drusen, geographic atrophy or neovascular AMD according to definitions used by the Eye Diseases Prevalence Research Group (EDPRG). The expected number of cases and standardised mortality ratio (SMR) for large drusen were estimated based on EDPRG estimates. RESULTS: We identified 177 patients aged ≥55 years as having primary non-infectious uveitis; 170 (96.0%) had gradable fundus photos. Average age was 65.0±7.5 years (range 55-87), and 87 were non-Hispanic white, 66 non-Hispanic black, 6 Hispanic white and 11 of other race/ethnicity. Large drusen were identified in four patients (2.4%; 95% CI 0.6 to 6.0). No patients were identified to have late AMD. In the uveitis cohort, the SMR for cases of large drusen, which was adjusted for age, was calculated to be 0.32 (95% CI 0.12 to 0.70) for the whole cohort, 0.28 (95% CI 0.09 to 0.79) for non-Hispanic whites and 0.46 (95% CI 0.14 to 1.29) for non-Hispanic blacks. CONCLUSIONS: Large drusen prevalence among patients with uveitis ≥55 years of age appears less than the prevalence in the general US population after accounting for differences in age distribution, especially for non-Hispanic whites. Although the racial and gender distribution in this study population is not directly representative of the general US population, results of this study suggest possible sparing of patients with uveitis from AMD. A larger systematic study with greater power would be needed to confirm these findings.

Preferred practice pattern in central serous chorioretinopathy.

PURPOSE: Central serous chorioretinopathy (CSC) management lacks well-defined guidelines given the variable natural history of this disease and the lack of prospective trials. We conducted an online preferred physician practice survey to track international trends and variations in the management of CSC data. METHODS: We designed and distributed an online 27-item questionnaire with secure confidential access to retina specialists with a publication record in CSC. Physicians with at least one publication as first or corresponding author in any national or international peer reviewed journal in the English language on CSC within the last 2 years on PubMed were included. Participants were masked to the responses from other participants. RESULTS: The response rate was 82.3% (107 out of 130). 79.1% physicians preferred to observe cases of acute CSC. For chronic cases, 66.7% offered photodynamic therapy (PDT) as first line treatment. The most commonly used PDT protocol was full dose and half-fluence (60.6%). For chronic cases with intraretinal cystic changes, 43.1% opted for observation. Enhanced depth imaging, optical tomography was a common diagnostic tool for 59.8%, while indocyanine green angiography was only used by 37.8%. One regional difference was a preference for focal laser in Asia for initial treatment. CONCLUSIONS: While there are some common practice patterns for of CSC, there are still variations in regional and individual practice patterns indicating the need to establish more definitive practice guidelines. This survey data could be useful to plan a prospective study to address many unanswered questions.

Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated With Ozurdex Trial.

PURPOSE: The Diabetic Macular Edema Treated with Ozurdex (DMEO) Trial measured aqueous pro-permeability factors (PPFs) in diabetic macular edema (DME) patients before and after injection of dexamethasone implant or vascular endothelial growth factor (VEGF)-neutralizing protein and correlated changes in levels with changes in excess foveal thickness (EFT) to identify potential PPFs contributing to DME. DESIGN: Prospective, randomized crossover clinical trial. METHODS: Twenty DME patients randomized to dexamethasone implant or VEGF-neutralizing protein had aqueous taps and spectral-domain optical coherence tomography (SDOCT) at baseline and every 4 weeks for 28 weeks. Aqueous levels of 55 vasoactive proteins were measured with protein array. Crossover at week 16 provided changes in protein levels after each intervention in all 20 patients. RESULTS: After dexamethasone implant there was significant correlation between changes in levels of 13 vasoactive proteins with changes in EFT, including 3 known PPFs: angiopoietin-2 (r = 0.40, P = .001), hepatocyte growth factor (HGF; r = 0.31, P = .02), and endocrine gland-VEGF (EG-VEGF, r = 0.43, P < .001). Reduction of prolactin, insulin-like growth factor binding protein-3, and matrix metalloproteinase-9 correlated with edema reduction after injection of a VEGF-neutralizing protein as well as dexamethasone implant, suggesting their modulation is likely secondary to changes in edema rather than causative. CONCLUSIONS: Correlation of edema reduction with reduction in the PPFs angiopoietin-2, HGF, and EG-VEGF provides potential insight into the multifactorial molecular mechanism by which dexamethasone implants reduce edema and suggest that additional study is needed to investigate the contributions of these 3 factors to chronic DME.

A Crossover Design for Comparative Efficacy: A 36-Week Randomized Trial of Bevacizumab and Ranibizumab for Diabetic Macular Edema.

PURPOSE: To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. DESIGN: Randomized, double-masked, 36-week, 3-period crossover clinical trial. PARTICIPANTS: Fifty-six subjects with DME involving the center of the macula in one or both eyes. METHODS: Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). MAIN OUTCOME MEASURES: Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. RESULTS: Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 µm for bevacizumab and -137 µm for ranibizumab (difference, 48 µm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 µm (95% CI, -155 to -100) for bevacizumab and -176 µm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next. CONCLUSIONS: This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab, ranibizumab, and aflibercept for DME. The 3-period crossover design allowed for meaningful and efficient comparison, suggesting that this approach may be useful for future comparative efficacy studies of anti-vascular endothelial growth factor drugs for DME.

Changes in Retinal Nonperfusion Associated with Suppression of Vascular Endothelial Growth Factor in Retinal Vein Occlusion.

PURPOSE: To assess changes in retinal nonperfusion (RNP) in patients with retinal vein occlusion (RVO) treated with ranibizumab. DESIGN: Secondary outcome measure in randomized double-masked controlled clinical trial. PARTICIPANTS: Thirty-nine patients with central RVO (CRVO) and 42 with branch RVO (BRVO). METHODS: Subjects were randomized to 0.5 or 2.0 mg ranibizumab every month for 6 months and then were re-randomized to pro re nata (PRN) groups receiving either ranibizumab plus scatter laser photocoagulation or ranibizumab alone for an additional 30 months. MAIN OUTCOME MEASURES: Comparison of percentage of patients with increased or decreased area of RNP in patients with RVO treated with 0.5 versus 2.0 mg ranibizumab, during monthly injections versus ranibizumab PRN, and in patients treated with ranibizumab PRN versus ranibizumab PRN plus laser. RESULTS: In RVO patients given monthly injections of 0.5 or 2.0 mg ranibizumab for 6 months, there was no significant difference in the percentage who showed reduction or increase in the area of RNP. However, regardless of dose, during the 6-month period of monthly injections, a higher percentage of patients showed a reduction in area of RNP and a lower percentage showed an increase in area of RNP compared with subsequent periods of ranibizumab PRN treatment. After the 6-month period of monthly injections, BRVO patients, but not CRVO patients, randomized to ranibizumab PRN plus laser showed significantly less progression of RNP compared with patients treated with ranibizumab PRN. CONCLUSIONS: Regardless of dose (0.5 or 2.0 mg), monthly ranibizumab injections promote improvement and reduce progression of RNP compared with PRN injections. The addition of scatter photocoagulation to ranibizumab PRN may reduce progression of RNP in patients with BRVO, but a statistically significant reduction was not seen in patients with CRVO.

OUTCOMES OF TREATMENT OF CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH CENTRAL SEROUS CHORIORETINOPATHY WITH INTRAVITREAL ANTIANGIOGENIC AGENTS.

PURPOSE: To report clinical characteristics and treatment outcomes from the largest case series of choroidal neovascularization secondary to central serous chorioretinopathy. METHODS: Retrospective analysis of 46 eyes of 43 consecutive subjects. Collected data included demographic details, history of presenting illness, clinical examination details including visual acuity at presentation and follow-up with imaging and treatment details. Main outcome measures were the proportion of eyes that had improved (3 or more lines), stable (within ±1 line), or decreased (3 or more lines) vision at the final visit as compared with baseline examination. Secondary efficacy outcomes included change in visual acuity at final follow-up, number of injections, treatment-free interval, and adverse events. RESULTS: Mean age was 57.56 years (range 29-79 years). Mean follow-up duration was 38.3 months ± 58.9 months. More than 3 lines of improvement in 12 eyes (26%), vision was stable (within ±1 line) in 19 eyes (41.3%), and >3 lines of loss was noted in 6 eyes (13%). Mean change in the number of lines was 1.16 ± 3.74. Mean number of anti-vascular endothelial growth factor injections during the follow-up was 4.45 ± 4.1. The longest treatment-free interval was 8.9 months ± 7.5 months. There were no adverse events noted. CONCLUSION: Anti-vascular endothelial growth factor therapy as a primary therapy for choroidal neovascularization secondary to central serous chorioretinopathy is safe and efficacious, without any serious adverse events.