TREATMENT OF VITREOMACULAR TRACTION WITH INTRAVITREAL PERFLUOROPROPANE (C3F8) INJECTION.

PURPOSE: To assess the posterior vitreous release rates following a single, office-based intravitreal injection of expansile gas in treating vitreomacular traction. METHODS: Thirty eyes of 29 consecutive patients with symptomatic vitreomacular traction received a single, office-based intravitreal injection of up to 0.3 mL of 100% perfluoropropane (C3F8). RESULTS: Overall, vitreomacular traction release occurred in 25 of 30 eyes by the final follow-up visit (83% final release rate); furthermore, 90% (9 of 10 eyes) with diabetes mellitus released, 83% (5 of 6 eyes) with concurrent epiretinal membrane released, and 83% (5 of 6 eyes) previously treated with ocriplasmin released. Vitreomacular traction release occurred overnight in some patients and was documented on spectral domain optical coherence tomography at an average of 13 days (range, 1-62 days). The phakic release rate was 89% (16 of 18 eyes) versus a 75% pseudophakic release rate (9 of 12 eyes) (P = 0.3173). Ellipsoid zone changes on spectral domain optical coherence tomography occurred in 1 of 30 gas-treated eyes. One patient developed pupillary block. CONCLUSION: Office-based intravitreal injection of C3F8 offers an inexpensive and effective treatment for vitreomacular traction, including for patients who underwent previous ocriplasmin administration and in patients with diabetes mellitus or epiretinal membrane.

SYSTEMIC PHARMACOKINETICS AND PHARMACODYNAMICS OF INTRAVITREAL AFLIBERCEPT, BEVACIZUMAB, AND RANIBIZUMAB.

PURPOSE: To evaluate the systemic pharmacokinetics (PKs) of aflibercept, bevacizumab, and ranibizumab in patients with neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO). METHODS: Prospective, open-label, nonrandomized clinical trial of patients with AMD, DME, or RVO who were antivascular endothelial growth factor (VEGF) naïve or had not received anti-VEGF for ≥4 months. Patients received 3 monthly intravitreal injections of aflibercept 2.0 mg, bevacizumab 1.25 mg, or ranibizumab (0.5 mg for AMD/RVO, 0.3 mg for DME). The main outcome measures were serum PKs and plasma free-VEGF concentrations after the first and third injections. RESULTS: A total of 151 patients were included. In AMD/DME/RVO, systemic exposure to each drug was highest with bevacizumab, then aflibercept, and lowest with ranibizumab. Ranibizumab cleared from the bloodstream more quickly than bevacizumab or aflibercept. Aflibercept treatment resulted in the greatest reductions in plasma free-VEGF relative to baseline levels, whereas ranibizumab treatment resulted in the smallest decreases in plasma free-VEGF. CONCLUSION: The three anti-VEGF treatments examined in this analysis demonstrated notable differences in systemic PKs. Generally, the reduction in plasma free-VEGF levels correlated with elevated levels of circulating anti-VEGF agents, with the reduction in free-VEGF levels greatest with aflibercept and least with ranibizumab.

Outer retina reflectivity changes on sd-oct after intravitreal ocriplasmin for vitreomacular traction and macular hole.

PURPOSE: To report initial experience with intravitreal ocriplasmin (IVO) and to describe outer retina reflectivity changes observed on spectral domain optical coherence tomography (SD-OCT) after IVO injection in patients with vitreomacular traction (VMT) with or without macular holes (MHs). METHODS: A consecutive retrospective review of patients with VMT and MH who were treated with IVO was performed. Patients underwent complete ophthalmic evaluation, including nonstandardized Snellen visual acuity testing, and SD-OCT at baseline and follow-up visits. RESULTS: A total of 23 patients who received IVO for VMT and/or MH were included for analysis. Patient age ranged from 53 years to 93 years with a mean of 74 years. The mean follow-up was 174 days (range: 20-291 days). Vitreomacular traction release at Day 30 after IVO was achieved in 11 of 23 patients (47.82%), at an average of 14.54 days (range: 1-30 days) after treatment. The mean visual acuity improved from 0.50 to 0.38. At presentation, eight patients had MH associated with VMT. Closure of the MH with ocriplasmin was achieved in two patients, and six patients underwent pars plana vitrectomy for MH repair. Ten of 23 patients (43.47%) presented with changes in the outer retina reflectivity on SD-OCT after IVO, 4 patients of this group experienced a decrease in visual acuity. In 7 of these 10 patients (70%), VMT release was documented on OCT by Day 30 postinjection compared with 4 of 13 patients (30.76%) without outer retina changes post-IVO. Normalization of the outer retina reflectivity was achieved in all cases. CONCLUSION: In this case series of VMT/MH patients treated with ocriplasmin, changes in the SD-OCT outer retina reflectivity were relatively common. Within weeks, the outer retinal reflectivity on SD-OCT improved, as did the visual acuity. Further studies to investigate the association between outer retina reflectivity changes with the use of IVO and long-term visual acuity outcomes are warranted.

Minority Stressors, Social Provisions, and Past-Year Suicidal Ideation and Suicide Attempts in a Sample of Sexual Orientation and Gender Identity/Expression Minority People in Canada.

Purpose: Mental health disparities in sexual orientation and/or gender identity and/or expression (SOGIE) minority groups are well-documented, with research consistently showing higher levels of suicidality, even in Canada, considered one of the world's most accepting countries of SOGIE minority groups. Adverse outcomes in these groups are often framed using minority stress theory, with social support frequently studied as an integral buffer to these outcomes. This analysis explores facets of minority stress and social support associated with past-year suicidal ideation and suicide attempts. Methods: A cross-sectional internet survey of SOGIE diverse people in Canada (n = 1542) was conducted. Binary logistic regression calculated bivariate and multivariate factors associated with past-year suicidal ideation and suicide attempts. Backward elimination (retaining sociodemographic factors and self-rated mental health) identified salient minority stress and social support (provisions) factors. Results: Over half (56.72%) of participants had ever thought of dying by suicide, with 24.84% having attempted suicide. During the past year, 26.80% had thought of dying by suicide, with 5.32% having attempted suicide. Victimization events, and guidance (e.g., someone to talk to about important decisions) and attachment (e.g., close relationships providing emotional security) social provision subscales remained salient after backward elimination procedures. Conclusion: Our findings emphasize that a fulsome, multilevel approach considering structural, community, and individual strategies to address overt discrimination, integrating social connections and guidance, is necessary to prevent dying by suicide.

The use and effects of telemedicine on complementary, alternative, and integrative medicine practices: a scoping review.

BACKGROUND: Telemedicine includes the delivery of health-care services and sharing of health information across distances. Past research has found that telemedicine can play a role in enhancing complementary, alternative, and integrative medicine (CAIM) while allowing the maintenance of cultural values and ancestral knowledge. This scoping review synthesized evidence regarding the use of telemedicine in the context of CAIM. METHODS: Following Arksey and O'Malley's scoping review framework, CINAHL, PsycINFO, MEDLINE, EMBASE and AMED databases were searched systematically. The CADTH website was also searched for grey literature. Eligible articles included a CAIM practice or therapy offered through telemedicine, with no restrictions placed on the type of telemedicine technology used. Inductive thematic analysis was conducted to synthesise common themes among the included studies. RESULTS: Sixty-two articles were included in this synthesis. The following themes emerged: 1) the practitioner view of CAIM delivered through telemedicine, 2) the patient view of CAIM delivered through telemedicine, and 3) the technological impacts of telemedicine delivery of CAIM. CONCLUSIONS: Studies have shown that telemedicine delivery of CAIM is feasible, acceptable, and results in positive health outcomes. Some barriers remain such as the presence of chronic illness and morbidity, inability to form strong patient-provider relationships relative to face-to-face approaches, and technological difficulties. Future intervention research should focus on reducing such barriers, as well as explore which patient population would realize the greatest benefit from CAIM delivered via telemedicine, and the impact of interventions on providers and caregivers.

The National and Global Impact of Systemic and Structural Violence on the Effective Prevention, Treatment, and Management of COVID-19 in African or Black Communities: Protocol for a Scoping Review.

BACKGROUND: As COVID-19 ravages the globe and cases increase rapidly, countries are presented with challenging policy choices to contain and mitigate its spread. In Canada and globally, the COVID-19 pandemic has added a new stratum to the debate concerning the root causes of global and racial health inequities and disparities. Individuals who exist as targets of systemic inequities are not only more susceptible to contracting COVID-19, but also more likely to bear the greatest social, economic, and physical burdens. Therefore, data collection that focuses on the impact of COVID-19 on the lives and health of African/Black communities worldwide is needed to develop intersectional, culturally relative, antiracist/antioppression, and empowerment-centered interventions and social policies for supporting affected communities. OBJECTIVE: The primary objective of this review is to investigate the impact and management of COVID-19 among African/Black individuals and communities, and understand how anti-Black racism and intersectional violence impact the health of African/Black communities during the pandemic. Moreover, the study aims to explore research pertaining to the impact of COVID-19 on Black communities in the global context. We seek to determine how Black communities are impacted with regard to structural violence, systematic racism, and health outcomes, and the ways in which attempts have been made to mitigate or manage the consequences of the pandemic and other injurious agents. METHODS: A systematic search of quantitative and qualitative studies published on COVID-19 will be conducted in MEDLINE (Ovid), Embase (Ovid), Cumulative Index to Nursing and Allied Health Literature (EBSCO), Cochrane Library, PsychInfo (Ovid), CAB Abstracts (Ovid), Scopus (Elsevier), Web of Science (Clarivate), and Global Index Medicus. To be included in the review, studies should present data on COVID-19 in relation to African/Black individuals, populations, and communities in the global sphere. Studies must discuss racism, oppression, antioppression, or systemic and structural violence and be published in English, French, Spanish, or Portuguese. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, the findings will be synthesized quantitatively and qualitatively through thematic analysis. The risk of bias will not be assessed. RESULTS: Title, abstract, and full-text screening concluded in June 2022. Data collection is in progress and is expected to be completed by December 2022. Data analysis and drafting of the manuscript will be done thereafter. Findings from the scoping review are expected to be provided for peer review in 2023. CONCLUSIONS: This review will collect important data and evidence related to COVID-19 in African/Black communities. The findings could help identify existing gaps in COVID-19 management in African/Black communities and inform future research paradigms. Furthermore, the findings could be applied to decision-making for health policy and promotion, and could potentially influence services provided by health care facilities and community organizations around the globe. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40381.

Intravitreal ranibizumab for macular edema secondary to central retinal vein occlusion.

PURPOSE: To evaluate the safety and efficacy of intravitreal ranibizumab for macular edema secondary to central retinal vein occlusion. METHODS: Patients with macular edema secondary to perfused central retinal vein occlusion were enrolled in this ongoing, prospective, open-label study. Treatment was initiated with monthly intravitreal ranibizumab for 3 months. In the first year, additional injections were administered for edema in quarterly intervals as needed (PRN) for Cohort 1 (n = 10) and monthly PRN for Cohort 2 (n = 10). In the second year of treatments, all patients received monthly PRN treatment. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, central retinal thickness, fundus photographs, and fluorescein angiograms were evaluated, and the incidence and severity of adverse events were documented. RESULTS: Mean change in best-corrected visual acuity and central retinal thickness improved during the induction phase in both groups. During the remainder of the first year for Cohort 1, initial gains were lost during quarterly treatment but returned with monthly PRN treatment in the second year. For Cohort 2, improvement in best-corrected visual acuity and central retinal thickness from the induction phase was maintained through Month 24. Nineteen of 20 patients experienced a reduction in intraretinal hemorrhage, optic nerve swelling, and/or venous diameter after treatment. One myocardial infarction, one cerebrovascular accident, and no serious ocular adverse events were reported. Iris neovascularization was developed in none of the eyes. CONCLUSION: Ranibizumab was well tolerated and associated with a greater reduction in macular edema and improvement in visual acuity in the monthly PRN regimen compared with quarterly treatment. Vision lost during the quarterly PRN injection intervals in the first year of Cohort 1 could be regained by switching to monthly PRN dosing.

Ranibizumab for the treatment of macular edema associated with perfused central retinal vein occlusions.

PURPOSE: Assessment of biological effect, visual acuity changes, and safety of intravitreal (IVT) ranibizumab in patients with macular edema associated with perfused central retinal vein occlusion (CRVO). DESIGN: Ongoing, prospective, open-label, single-center, uncontrolled study. PARTICIPANTS: Ten adult patients with macular edema associated with perfused CRVO. METHODS: Patients were randomly assigned to receive 3 monthly IVT injections of either 0.3 or 0.5 mg ranibizumab (n = 5 at each dose). Additional injections were administered quarterly as needed over the ensuing 21 months at the physician's discretion for recurrent or persistent macular edema. MAIN OUTCOME MEASURES: The predetermined primary endpoint was the percentage of patients gaining >or=15 letters of best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity (BCVA). The secondary endpoints include the mean change in BCVA and central retinal thickness (CRT) measured by optical coherence tomography, the rate of progression to ischemic CRVO, extent of intraocular hemorrhage, retinal vein diameter, optic nerve head swelling, and the incidence and severity of ocular and nonocular adverse events. RESULTS: After 3, 6, and 9 months of follow-up, 40%, 10%, and 30% of patients, respectively, gained >or=15 letters in BCVA; mean BCVA improved by 12+/-20 letters, 3+/-21 letters, and 1+/-24 letters, respectively, compared with baseline; CRT showed a mean decrease of 272+/-244 microm, 88+/-178 microm, and 119+/-153 microm, compared with baseline. No significant differences were observed between the 0.3- and 0.5-mg doses. Most patients experienced decreases in the extent of retinal hemorrhage, retinal vein diameter, and optic nerve head swelling at months 3 and 6 compared with baseline. No patients progressed to ischemic CRVO or experienced a severe adverse event that was attributed to ranibizumab. CONCLUSIONS: Ranibizumab is generally well-tolerated and may improve BCVA and decrease CRT. The improvements in BCVA and CRT observed during the initial monthly injection period (0 to 3 months) were possibly lost to the recurrence of macular edema in between ranibizumab injection during the quarterly treatments (3 to 9 months). The extent of retinal hemorrhage, retinal vein diameter, and nerve swelling continued to normalize for most of the patients from baseline to 6 months. Follow-up is ongoing, and alternative dosing regimens are being evaluated.

Evaluation of the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease.

PURPOSE: To compare the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease. DESIGN: Retrospective comparative interventional case series. SETTINGS: Nine international uveitis specialty clinics. STUDY POPULATION: Forty-eight patients presenting over a three-year period to a study center with acute Vogt-Koyanagi-Harada disease. INTERVENTION: Initial treatment with corticosteroid either orally (Oral only group) or intravenously followed by an oral taper (IV+Oral group). MAIN OUTCOME MEASURES: Change in visual acuity with treatment; development of ocular complications, including visually significant cataract, choroidal neovascularization, subretinal fibrosis, fundus pigment migration, nummular hypopigmented lesions, and diffuse fundus depigmentation; use of immunosuppressive therapy. RESULTS: The Oral only group comprised 15 patients (31%) and the IV+Oral group 33 patients (69%). Median follow-up was 15 months. There was no difference in duration of follow-up between groups (P = .234). There was no difference in the change in visual acuity between groups, adjusting for initial visual acuity (P = .402). There were no differences in the rates of development of visually significant cataract, fundus pigmentary changes, or in the rate of use of subsequent immunosuppressive therapy between treatment groups. No patients developed choroidal neovascularization or subretinal fibrosis over the study period. CONCLUSIONS: Route of administration of corticosteroid had no detectable effect on change in visual acuity nor on the development of visually significant complications over the study period. Prospective trials are necessary to address speed of resolution and definitively answer outcome questions.

Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-angle glaucoma.

PURPOSE: To design an instrument to selectively remove trabecular meshwork and Schlemm's canal inner wall (SCIW), and demonstrate its effectiveness by histologic analysis of treated cadaveric human tissue. METHODS: The design parameters of the instrument were the ability to permanently remove a segment of trabecular meshwork and Schlemm's canal inner wall without causing damage to surrounding tissue, and to allow use with standard anterior segment surgical techniques and equipment via an ab interno approach. Treatment was applied to 20 segments of human corneoscleral rims. The treated areas were examined using a confocal microscope and compared with matching areas in untreated controls and simulated goniotomy. RESULTS: The resultant instrument system surgically removes the trabecular meshwork and Schlemm's canal inner wall from an anterior chamber approach. It consists of a disposable surgical handpiece with irrigation, aspiration, and electrocautery to focally ablate the target tissues. The attached console includes a high-frequency (550 KHz) electrosurgical generator and irrigation/aspiration controlled by a foot pedal. Histologic examination of specimens treated with the Trabectome displayed disruption of the trabecular meshwork and Schlemm's canal inner wall without damage to surrounding structures. The specimens treated by simulated goniotomy displayed significant damage to the outer wall of Schlemm's canal and the surrounding sclera. The controls showed no disruption or damage to any tissues. CONCLUSIONS: The Trabectome system is designed for performing trabeculectomy via an ab interno approach. It successfully removed sections of trabecular meshwork and Schlemm's canal inner wall with less injury to the adjacent tissue compared with goniotomy knife in vitro. Theoretically, this procedure should provide direct access of aqueous humor to Schlemm's canal.

Unilateral clinical anophthalmia with optic nerve hypoplasia in the fellow eye.

We present the clinical and radiologic findings of two cases of clinical anophthalmia in one eye and optic nerve hypoplasia in the other eye. We propose possible causes of this rare finding.

Evaluation of subconjunctival triamcinolone for nonnecrotizing anterior scleritis.

PURPOSE: Subconjunctival corticosteroid injection (SCI) for nonnecrotizing anterior scleritis remains controversial, partly because long-term follow-up is not available. This study documents the efficacy and adverse effects of SCI. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Thirty-eight eyes of 35 patients with nonnecrotizing, noninfectious anterior scleritis resistant to prior systemic or local therapy. INTERVENTION: Subconjunctival triamcinolone acetonide injection. MAIN OUTCOME MEASURE: Persistence or resolution of signs and symptoms of anterior scleritis and development of complications. RESULTS: Thirty-six of 38 eyes had complete resolution of signs and symptoms within 6 weeks of SCI. Fifteen eyes had follow-up of > or =30 months. There were no instances of scleral melting or perforation; adverse events included subconjunctival hemorrhage (5 patients), transient ocular hypertension without evidence of glaucoma (4 patients), cataract (2 patients), and glaucoma (2 patients). Subconjunctival corticosteroid injection resulted in reduced dependence on systemic medications. CONCLUSION: Subconjunctival corticosteroid injection in eyes that failed other therapies is effective, reduces dependence on systemic medications, and did not result in scleral necrosis over a median follow-up period of 29 months.

Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series.

PURPOSE: To assess the feasibility of a study design that may determine whether subcutaneous administration of the interleukin-2 receptor antibody daclizumab can safely reduce the dependence on standard systemic corticosteroids or other immunosuppressive regimens in patients with sight-threatening, noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Prospective, multicenter, nonrandomized, noncomparative, open-label interventional trial. PARTICIPANTS: Fifteen patients, 5 each at 3 clinical centers, with noninfectious intermediate, posterior, or panuveitis, who require a currently stable immunosuppression regimen of systemic corticosteroids and/or other systemic treatments to control noninfectious intraocular inflammation. METHODS: After enrollment and baseline ophthalmic evaluations, 2 induction treatments were given 2 weeks apart using subcutaneous (SC) daclizumab at 2 mg/kg. Subcutaneous daclizumab maintenance treatments were then continued every 2 weeks at 1 mg/kg for 6 months. The initial immunosuppression load was tapered over 8 to 12 weeks in a staggered fashion beginning with the first induction treatment. Safety evaluations were performed at each treatment visit, with a primary efficacy evaluation at 12 weeks and a repeat efficacy evaluation at 26 weeks. MAIN OUTCOME MEASURES: Best-corrected visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] method) with a concurrent taper of concomitant systemic immunosuppression medication load (tabulated by use of a weighted scoring system) was assessed; target for success was defined as a 50% or greater reduction in concomitant immunosuppression load by 12 weeks while maintaining visual acuity within 5 ETDRS letters of baseline. Ocular inflammation was assessed at each visit with standardized grading scales. RESULTS: Ten of 15 patients (67%) receiving SC daclizumab treatments every other week successfully achieved the primary efficacy end point of reducing their concomitant immunosuppression load by at least 50% while maintaining their baseline visual acuity at 12 and 26 weeks. Subcutaneous daclizumab injections were well tolerated with no serious adverse events observed during the 6 months of treatments, although 3 patients experienced possibly related, nonserious adverse events. CONCLUSIONS: Subcutaneous daclizumab induction treatments at 2 mg/kg followed by 1 mg/kg maintenance treatments every other week seems safe and, in most cases, may reduce the concomitant immunosuppressive load required to treat noninfectious uveitis for 12 to 26 weeks.

HLA-DRB1 and -DQB1 alleles in mestizo patients with Vogt-Koyanagi-Harada's disease in Southern California.

We evaluated human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles as genetic markers for Vogt-Koyanagi-Harada (VKH) disease in Mestizo patients in Southern California. Mestizo individuals with VKH disease (n = 29) at two institutions were evaluated. Typing of HLA-DRB1 and DQB1 genes was performed using DNA-based techniques. Gene frequencies were compared to Mestizo individuals living in Southern California. All patients had HLA-DRB1*01, DRB1*04, DQB1*03 or DQB1*05, or a combination of these genes. The gene frequency of combined HLA-DR4 alleles was increased when compared to controls. The frequencies of HLA-DRB1*0404 and DRB1*0407 were increased compared to controls, but were not significant after Bonferroni correction. Three patients had the HLA-DRB1*0410 allele; this allele was not found in controls. All HLA-DRB1*01 positive patients had the DRB1*0102 subtype. No HLA-DQB1 allele was significantly increased compared to controls. This study is the first to identify a possible association between HLA-DRB1*0404 and VKH disease, as well as to find DRB1*0102 and DRB1*0410 in Mestizo patients.

Human leukocyte antigen A29 subtypes associated with birdshot retinochoroidopathy.

PURPOSE: To determine whether birdshot retinochoroidopathy is associated with subtypes of the human leukocyte antigen (HLA)-A29 other than HLA-A*2902. DESIGN: Experimental study. METHODS: High-resolution DNA typing of HLA-A29 subtypes was performed on blood from 20 subjects with birdshot retinochoroidopathy using polymerase chain reaction-based typing methods. Results were compared with published controls. RESULTS: Four of 20 subjects (20%) had the HLA-A*2901 allele; two were homozygous for HLA-A*29, and both had the HLA-A*2901 and HLA-A*2902 alleles. Among 18 subjects with only one HLA-A*29 allele, the HLA-A*2902 allele was found in 16 (89%) and the HLA-A*2901 allele was found in two (11%). No subject was found to have HLA-A*2903, HLA-A*2904, HLA-A*2905, or HLA-A*2906. CONCLUSIONS: Both HLA-A*2901 and HLA-A*2902 are associated with birdshot retinochoroidopathy. Our data do not support the previous suggestion that the HLA-A29.1 serotype may be protective against development of birdshot retinochoroidopathy. Additional studies will be required to determine whether the other, less common subtypes are associated with the disease. HLA-A29 subtype testing is not required for the clinical evaluation of HLA-A29-positive patients with birdshot retinochoroidopathy.

Update of ocular manifestations in sarcoidosis.

Although the lung is the primary target of involvement, sarcoidosis can involve any organ in the body, including the eye. Ocular involvement may also be the initial manifestation of sarcoidosis in many patients. Since no characteristic clinical feature heralds the onset of ocular involvement in sarcoidosis, a systematic eye examination is advised. This review discusses ocular manifestations and changes based upon the anatomic site of the eye, ocular tissue biopsy, and treatment. Early recognition and intervention are essential for the reduction of ocular morbidity and the improvement of the patient's quality of life.

Cytomegalovirus retinitis in the era of combined highly active antiretroviral therapy.

Advancements in antiretroviral therapy have changed the way we view and treat cytomegalovirus retinitis (CMVR). At one time the diagnosis of CMVR necessitated that most patients undergo daily intravenous infusions of anti-CMV agents. Today, after the restoration of their immune systems, they are able to stop maintenance anti-CMV therapy. HAART failure, resistant strains of CMV, and immune recovery uveitis are growing challenges.

Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD.

BACKGROUND: Data comparing systemic exposure and systemic vascular endothelial growth factor (VEGF) suppression of ranibizumab, bevacizumab and aflibercept following intravitreal injection are lacking. METHODS: Fifty-six patients with wet age-related macular degeneration received intravitreal ranibizumab (0.5 mg), bevacizumab (1.25 mg), or aflibercept (2.0 mg). Serum pharmacokinetics and plasma free VEGF were evaluated after the first and third injections. RESULTS: Following the first dose, systemic exposure to aflibercept was 5-, 37-, and 9-fold higher than ranibizumab, whereas, bevacizumab was 9-, 310-, and 35-fold higher than ranibizumab, based on geometric mean ratio of peak and trough concentrations and area under the curve, respectively. The third dose showed accumulation of bevacizumab and aflibercept but not ranibizumab. Aflibercept substantially suppressed plasma free VEGF, with mean levels below lower limit of quantitation (10 pg/mL) as early as 3 h postdose until ≥7 days postdose. Mean free (unbound) VEGF levels with ranibizumab were largely unchanged, with mean trough level of 14.4 pg/mL compared with baseline of 17 pg/mL. CONCLUSIONS: There are notable differences in systemic pharmacokinetics and pharmacodynamics among anti-VEGF treatments after intravitreal administration. All three agents rapidly moved into the bloodstream, but ranibizumab very quickly cleared, whereas bevacizumab and aflibercept demonstrated greater systemic exposure and produced a marked reduction in plasma free VEGF. TRIAL REGISTRATION NUMBER: NCT02118831.