Comparison of endophthalmitis rates following intravitreal injection of compounded bevacizumab, ranibizumab, and aflibercept.

OBJECTIVE: Whereas the incidence of endophthalmitis after compounded intravitreal bevacizumab is known to be low, the rates of endophthalmitis after intravitreal injection of compounded ranibizumab and aflibercept are not known. The purpose of this study was to determine the incidence of endophthalmitis after treatment with compounded intravitreal ranibizumab and aflibercept and to compare this to the incidence with compounded intravitreal bevacizumab. DESIGN: Retrospective chart review. PARTICIPANTS: All patients with post-injection endophthalmitis who were seen over a 6.5-year period at a tertiary retina referral practice. METHODS: We identified all cases of endophthalmitis by searching for patients who received intravitreal antibiotics and had antecedent intravitreal injection of bevacizumab, ranibizumab, or aflibercept. RESULTS: A total of 54,101 injections of bevacizumab, 5,614 injections of ranibizumab, and 3,468 injections of aflibercept were performed. The incidence of suspected endophthalmitis was 0.041% (95% CI: 0.026-0.062) for bevacizumab, 0.036% (95% CI: 0.0043-0.13) for ranibizumab, and 0.06% (95% CI: 0.007-0.2) for aflibercept. For culture-positive cases, the incidence was 0.017% (95% CI: 0.0076-0.032) for bevacizumab, 0.02% (95% CI: 0.0005-0.1) for ranibizumab, and 0.03% (95% CI: 0.0007-0.2) for aflibercept. There was no statistically significant difference in endophthalmitis rate between the 3 different compounded drugs with respect to both overall suspected endophthalmitis rate and culture-positive endophthalmitis rate (p = 0.87). CONCLUSION: Compounding of ranibizumab and aflibercept for intravitreal use appears to be safe because the endophthalmitis rate does not appear to be different from that of intravitreal bevacizumab.

Alterations in intraocular cytokine levels following intravitreal ranibizumab.

OBJECTIVE: Our previous work has shown that, after intravitreal bevacizumab (IVB) administration, decreases in the levels of vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF), along with increases in the levels of interleukin (IL)-8 and transforming growth factor (TGF)-ß2, can be observed. It is not yet known if similar changes occur after intravitreal ranibizumab (IVR). The purpose of this study was to examine intraocular cytokine changes after IVR. DESIGN: Prospective clinical study. PARTICIPANTS: Subjects with proliferative diabetic retinopathy requiring pars plana vitrectomy (PPV) were recruited. METHODS: Participants received IVR as pre-treatment before PPV. Aqueous humour levels of IL-8, VEGF-A, PlGF, and TGF-ß2 were measured at time of pre-treatment and PPV. Results were analyzed using univariate statistical models. RESULTS: A total of 14 participants were recruited. After IVR administration, we observed a decrease in the levels of VEGF-A and PlGF, and an increase in the levels of IL-8 and TGF-ß2. These results were statistically significant only for VEGF-A (p = 0.0001) and IL-8 (p = 0.0002). CONCLUSIONS: The changes in cytokine levels after IVR mirror the changes seen after IVB. Further studies are warranted in order to determine if there are any differences between IVB and IVR in this regard.

Real-world assessment of intravitreal dexamethasone implant (0.7 mg) in patients with macular edema: the CHROME study.

BACKGROUND: The purpose of this study was to evaluate the real-world use, efficacy, and safety of one or more dexamethasone intravitreal implant(s) 0.7 mg (DEX implant) in patients with macular edema (ME). METHODS: This was a retrospective cohort study of patients with ME secondary to retinal disease treated at ten Canadian retina practices, including one uveitis center. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), glaucoma and cataract surgery, and safety data were collected from the medical charts of patients with ≥3 months of follow-up after the initial DEX implant. RESULTS: One hundred and one patient charts yielded data on 120 study eyes, including diagnoses of diabetic ME (DME) (n=34), retinal vein occlusion (RVO, n=30; branch in 19 and central in 11), and uveitis (n=23). Patients had a mean age of 60.9 years, and 73.3% of the study eyes had ME for a duration of ≥12 months prior to DEX implant injection(s). Baseline mean (± standard error) BCVA was 0.63±0.03 logMAR (20/86 Snellen equivalents) and mean CRT was 474.4±18.2 µm. The mean number of DEX implant injections was 1.7±0.1 in all study eyes; 44.2% of eyes had repeat DEX implant injections (reinjection interval 2.3-4.9 months). The greatest mean peak changes in BCVA lines of vision occurred in study eyes with uveitis (3.3±0.6, P<0.0001), followed by RVO (1.3±0.5, P<0.01) and DME (0.7±0.5, P>0.05). Significant decreases in CRT were observed: -255.6±43.6 µm for uveitis, -190.9±23.5 µm for DME, and -160.7±39.6 µm for RVO (P<0.0001 for all cohorts). IOP increases of ≥10 mmHg occurred in 20.6%, 24.1%, and 22.7% of DME, RVO, and uveitis study eyes, respectively. IOP-lowering medication was initiated in 29.4%, 16.7%, and 8.7% of DME, RVO, and uveitis study eyes, respectively. Glaucoma surgery was performed in 1.7% of all study eyes and cataract surgery in 29.8% of all phakic study eyes receiving DEX implant(s). CONCLUSION: DEX implant(s) alone or combined with other treatments and/or procedures resulted in functional and anatomic improvements in long-standing ME associated with retinal disease.

A randomized study comparing the efficacy of bevacizumab and ranibizumab as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy.

BACKGROUND AND OBJECTIVE: To compare intravitreal bevacizumab versus ranibizumab as adjuvant treatment prior to pars plana vitrectomy (PPV) in proliferative diabetic retinopathy (PDR) with respect to parameters of surgical complexity. PATIENTS AND METHODS: Prospective, randomized, double-masked pilot study of patients requiring PPV for nonclearing vitreous hemorrhage or tractional retinal detachment (TRD) secondary to PDR. Patients were randomized to receive either intravitreal bevacizumab or ranibizumab at standard doses 1 week preoperatively. Measured parameters included total surgical time, presence of TRD, intraoperative bleeding, iatrogenic retinal breaks, and use of endolaser and endodiathermy or silicone oil. RESULTS: A total of 29 patients were recruited. For surgical parameters, there were no statistically significant differences between the groups in the univariate analyses. Multivariable analysis showed no statistically significant difference for total surgical time. CONCLUSION: This pilot study suggests that intravitreal bevacizumab and ranibizumab are equivalent as surgical adjuvants when used as pre-treatment in patients with PDR undergoing PPV.

Optical coherence tomography-based measurement of drusen load predicts development of advanced age-related macular degeneration.

PURPOSE: To determine whether baseline drusen load, as measured using spectral-domain optical coherence tomography (SD OCT), is a useful predictor of development of advanced age-related macular degeneration (AMD). DESIGN: Retrospective cohort study. METHODS: setting: Academic clinical practice. study population: All patients with non-neovascular AMD and no retinal pigment epithelial (RPE) atrophy at baseline who were seen between 2007 and 2012 in a single academic retina practice. A minimum of 1 year of follow-up was required. observation: Drusen load (area and volume) was assessed using automated SD OCT software algorithms. main outcome measure: RPE atrophy area, assessed using an automated SD OCT software algorithm, and the development of neovascular AMD. RESULTS: Eighty-three patients met the inclusion criteria with a mean age of 80 years and a mean follow-up time of 2.8 years. Repeated-measures analysis of variance showed an association between drusen area (P = .005) and drusen volume (P = .001) and the development of RPE atrophy. We also found an association between drusen area (P = .001) and drusen volume (P = .001) and the development of neovascular AMD. CONCLUSIONS: Drusen load, as measured using SD OCT, is associated with the development of RPE atrophy and neovascular AMD. SD OCT assessments of drusen load are simple and practical measurements that may be useful in stratifying the risk of developing advanced AMD. These measurements have potential applications in both routine clinical care and clinical trials.

Exacerbation of choroidal and retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration.

PURPOSE: To study the progression of retinal pigment epithelium (RPE) and choroidal atrophy in patients with neovascular age-related macular degeneration (AMD) and to assess for a possible association with the number and type of anti-vascular endothelial growth factor treatments. METHODS: Patients with neovascular AMD and a minimum of 1-year follow-up were reviewed. Fellow eyes with nonneovascular AMD were used as control eyes. Retinal pigment epithelial atrophy area and choroidal thickness were determined using spectral-domain optical coherence tomography. Multivariable regression models were used for statistical analyses. RESULTS: A total of 415 eyes were included in the study, with a mean follow-up of 2.2 years. Eyes with neovascular AMD had greater progression of RPE atrophy and choroidal atrophy compared with those with nonneovascular AMD (P < 0.001). Progression of RPE atrophy and choroidal atrophy was independently associated with the total number of injections of bevacizumab and ranibizumab (all P values ≤ 0.001). In the subgroup of 84 eyes with neovascular AMD and without RPE atrophy at baseline, only bevacizumab was associated with the progression of RPE atrophy (P = 0.003). This study likely lacked statistical power to detect an association with ranibizumab in this subgroup. CONCLUSION: Retinal pigment epithelial atrophy and choroidal atrophy in neovascular AMD seem to be exacerbated by anti-vascular endothelial growth factor treatment. Possible differences between bevacizumab and ranibizumab require further investigation.

Automatic detection of subretinal fluid and sub-retinal pigment epithelium fluid in optical coherence tomography images.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Subretinal fluid (SRF) and sub-retinal pigment epithelium (sub-RPE) fluid are signs of AMD and can be detected in optical coherence tomography images. However, manual detection and segmentation of SRFs and sub-RPE fluids are laborious and time consuming. In this paper, a novel pipeline is proposed for automatic detection of SRFs and sub-RPE fluids. First, top and bottom layers of retina are segmented using a graph cut method. Then, a Split Bregman-based segmentation method is used to segment dark regions between layers. These segmented regions are considered as potential fluid candidates, on which a set of features are generated. After that, a random forest classifier is trained to distinguish between the true fluid regions from the falsely detected fluid regions. This method shows reasonable performance in a leave-one-out evaluation using a dataset from 21 patients.

Relationship between systemic cytokines and complement factor H Y402H polymorphism in patients with dry age-related macular degeneration.

PURPOSE: To investigate the relationship between systemic cytokines, the complement factor H (CFH) Y402H polymorphism, drusen load, and subfoveal choroidal thickness in patients with dry age-related macular degeneration (AMD). DESIGN: Cross-sectional study. METHODS: Forty-four dry AMD patients under care of the Retina Service at the University of British Columbia were enrolled. Drusen load was measured with an automated software algorithm in spectral-domain optical coherence tomography; subfoveal choroidal thickness was measured manually using enhanced depth imaging. Bio-Plex suspension assays (Bio-Rad Laboratories) were used to analyze cytokines in plasma and CFH Y402H was genotyped. Statistical analyses included analysis of covariance and Pearson correlation, corrected for multiple comparisons. RESULTS: The levels of 3 of 4 studied cytokines were significantly different among patients with CC, CT, or TT variants of the CFH Y402H polymorphism (P < .01). Patients with the at-risk CC variant had higher systemic levels of interleukin-6, interleukin-18, and tumor necrosis factor α than those with the CT variants, the TT variant, or both (P < .01). Interleukin-1ß did not reach significance (P = .02), but did demonstrate a consistent trend. No correlation was found between plasma cytokines and drusen load or choroidal thickness (all P > .15). CONCLUSIONS: The elevated systemic levels of selected proinflammatory cytokines, including those representing products of inflammasome activation, were associated with the CC at-risk variant of the Y402H polymorphism and suggest that genetic factors regulate the inflammatory status in dry AMD patients. Our data support the central role of inflammation in the pathogenesis of AMD and provide further evidence of a systemic involvement in AMD etiology.

Uveitis risk following oral fluoroquinolone therapy: a nested case-control Study.

OBJECTIVE: To determine the risk of uveitis associated with the use of oral fluoroquinolones. METHODS: Nested case-control study of all patients who visited an ophthalmologist in British Columbia, Canada, between 2000 and 2007, as captured in the British Columbia Health Linked Database. RESULTS: A total 3383 incident cases of uveitis and 33,830 corresponding controls were identified. Among patients who had used oral fluoroquinolones within the past 30 days, the adjusted relative risk of uveitis was 3.53 (95% CI, 2.84-4.39). However, the relative risk of uveitis among patients taking oral macrolides and beta-lactams was also significantly elevated. CONCLUSIONS: Our data do not provide convincing evidence of an association between fluoroquinolones and uveitis, as this study found an association between several classes of antibiotics and uveitis. It is possible that the systemic processes for which these antibiotics are being prescribed are in fact the inciting factors for the uveitis.

Optical coherence tomography-based correlation between choroidal thickness and drusen load in dry age-related macular degeneration.

PURPOSE: Spectral domain optical coherence tomography can be used to measure both choroidal thickness and drusen load. The authors conducted an exploratory study using spectral domain optical coherence tomography to determine if a correlation between choroidal thickness and drusen load exists in patients with dry age-related macular degeneration. METHODS: Forty-four patients with dry age-related macular degeneration were recruited. The drusen area and volume were determined using the automated software algorithm of the spectral domain optical coherence tomography device, and choroidal thickness was measured using enhanced depth imaging. Correlations were determined using multivariable and univariable analyses. RESULTS: The authors found an inverse correlation between choroidal thickness and drusen load (r = -0.35, P = 0.04). Drusen load was also correlated with visual acuity (r = 0.32, P = 0.04). A correlation between choroidal thickness and visual acuity was suggested (r = -0.22, P = 0.21). CONCLUSION: Spectral domain optical coherence tomography can be used to assess the correlation between drusen load and choroidal thickness, both of which show a relationship with visual acuity. The measurement of these outcomes may serve as important outcome parameters in routine clinical care and in clinical trials for patients with dry age-related macular degeneration.

Comparative analysis of repeatability of manual and automated choroidal thickness measurements in nonneovascular age-related macular degeneration.

PURPOSE: We compared the reproducibility and mutual agreement of the subfoveal choroidal thickness measurements by expert raters and an automated algorithm in enhanced depth imaging optical coherence tomography (EDI-OCT) images of eyes with nonneovascular age-related macular degeneration (AMD). METHODS: We recruited 44 patients with nonneovascular AMD and EDI-OCT images were acquired. Subfoveal choroidal thickness was measured manually by two expert raters and automatically by a graph-cut-based algorithm. Drusen area was measured using the automated software (version 6) of Cirrus SD-OCT. The manual and automated choroidal thickness measurements were compared in reproducibility, mutual agreement, and correlation with drusen area. RESULTS: The mean subfoveal choroidal thickness was 246 ± 63 µm for the first rater, 214 ± 68 for the second rater, and 209 ± 53 for the automated algorithm. Intraclass correlation coefficients (ICC) and 95% confidence intervals (CI) were 0.96 (CI 0.94-0.98) between the raters, 0.85 (CI 0.77-0.90) between the first rater and the automated algorithm, and 0.84 (CI 0.75-0.89) between the second rater and the automated algorithm. Repeat scan measurement ICCs were 0.91 (CI 0.86-0.94) for the first rater, 0.96 (CI 0.94-0.97) for the second rater, and 0.87 (CI 0.80-0.92) for the automated algorithm. Manual and automated measurements were correlated with drusen area. CONCLUSIONS: The automated algorithm generally yielded smaller choroidal thickness than the raters with a moderate level of agreement. However, its repeat scan measurement repeatability was comparable to that of the manual measurements. The mean difference between the raters indicated possible biases in different raters and rating sessions. The correlation of the automated measurements with the drusen area was comparable to that of the manual measurements. Automated subfoveal choroidal thickness measurement has potential use in clinical practice and clinical trials, with possibility for reduced time and labor cost.

Very minimal fluence photodynamic therapy for chronic central serous chorioretinopathy.

OBJECTIVE: To describe the safety and efficacy of very minimal fluence photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). DESIGN: Retrospective case series. PARTICIPANTS: Five patients with chronic CSC. Two had previously failed alternative therapies, and one was taking concomitant corticosteroids. METHODS: Patients were treated with very minimal fluence PDT (12 J/cm(2), 150 mW/cm(2), for 80 seconds). Median follow-up time after PDT was 100 days (range, 51 to 154). RESULTS: All patients experienced an improvement in visual acuity and symptoms, as well as complete resolution of subretinal fluid. CONCLUSIONS: Very minimal fluence PDT appears to be a safe and effective treatment for chronic CSC. Based on these preliminary findings, a randomized controlled trial is warranted.

Tranexamic acid in the treatment of pediatric traumatic hyphema.

BACKGROUND: This study was undertaken to determine whether a difference exists in treatment outcome between patients treated with tranexamic acid (TEA) plus topical steroids and those treated with topical steroids alone. METHODS: A retrospective cohort study was conducted to compare treatment results for children with traumatic hyphema treated with TEA and topical steroids versus topical steroids alone. Patients were identified from a chart review of the Children's Hospital of Eastern Ontario eye clinic and the Queen's Department of Ophthalmology emergency eye clinic for charts coded "traumatic hyphema." The primary outcomes measured included visual acuity, rebleed rate, intraocular pressure, and time to hyphema resolution. Covariates were hyphema grade, the need for medications to lower intraocular pressure, and the presence of associated ocular traumatic complications. Analysis was performed with both bivariate analysis and multivariate models. RESULTS: Two hundred and fifteen patients with traumatic hyphema were included in our study. One hundred and thirty-seven patients (63.1%) received TEA plus topical steroids, and the remaining 78 patients received topical steroids alone. There was no significant difference in rebleed rate between the TEA plus topical steroid group (1.6%) and the steroid-alone group (2.6%, p = 0.60). INTERPRETATION: Patients with traumatic hyphema treated with TEA plus topical steroids did not have a significantly lower incidence of rebleed than those treated with topical steroids alone.

Myopia and astigmatism in retinopathy of prematurity after treatment with cryotherapy or laser photocoagulation.

BACKGROUND: Visual outcome studies have shown that laser photocoagulation may result in more favourable clinical outcomes than cryotherapy in threshold retinopathy of prematurity (ROP). Comparative refractive outcome studies have shown that patients treated with laser photocoagulation have less myopia than those treated with cryotherapy. We carried out a study to determine whether a difference in visual outcome or refraction exists in patients with threshold ROP who have been treated with cryotherapy vs. laser photocoagulation. METHODS: A retrospective cohort study was conducted comparing treatment results after at least 3 years of follow-up in patients with threshold ROP treated with cryotherapy or laser photocoagulation at a tertiary care children's hospital. Visual acuity and refraction were the outcomes studied. Covariates measured were sex, gestational age and birth weight. Analysis was performed with both bivariate analysis and multivariate models. RESULTS: Seventy-one eyes of 37 patients with threshold ROP were included in the study. Thirty-seven eyes received cryotherapy, and 34 eyes received laser photocoagulation. The mean spherical equivalent refraction was significantly lower in the cryotherapy group than in the laser photocoagulation group (-9.21 dioptres vs. -1.80 dioptres, p = 0.001). Patients in the cryotherapy group were more likely than those in the laser photocoagulation group to have against-the-rule astigmatism (odds ratio 6.86, p = 0.004). Laser photocoagulation did not significantly lower the frequency of an unfavourable visual outcome (visual acuity worse than 20/200) (p = 0.09). INTERPRETATION: Eyes with threshold ROP treated with laser photocoagulation were significantly less myopic and less likely to have against-the-rule astigmatism than those treated with cryotherapy.

Intraocular pressure after bilateral cataract surgery using Healon, Healon5, and Healon GV.

PURPOSE: To determine whether there is a difference in frequency or severity of postoperative intraocular pressure (IOP) spikes after bilateral phacoemulsification with complete ophthalmic viscosurgical device (OVD) removal when Healon5 (sodium hyaluronate 2.3%), Healon (sodium hyaluronate 1%), or Healon GV (sodium hyaluronate 1.4%) is used. SETTING: York Finch Eye Associates and Humber River Regional Hospital, Toronto, Ontario, Canada. METHODS: Bilateral cataract surgery was performed in 99 patients; 50 were randomly assigned to receive Healon5 in 1 eye and Healon GV in the fellow eye and 49, Healon in 1 eye and Healon GV in the fellow eye. The IOP was measured preoperatively as well as 5 and 24 hours and 7 days postoperatively. The mean IOP and standard deviation at each time interval were calculated for each OVD. The results were compared among the OVDs using Student t tests for each time at which IOP was assessed. RESULTS: There were no significant differences in postoperative IOP spikes among the Healon5, Healon, and Healon GV groups; however, patients receiving lower viscosity OVDs had a lower mean IOP at 24 hours. All groups had increased IOP at 5 and 24 hours and reduced IOP at 7 days. CONCLUSIONS: Within a family of molecularly similar OVDs, lower viscosity OVDs appear to cause slightly lower mean elevations in IOP in normal patients at 24 hours. However, if the OVD is removed, postoperative IOP spikes above 21 mm Hg appear related more to patient factors (eg, predisposition in glaucoma patients) and surgically induced trauma than to the specific long-chain non-cross-linked hyaluronan OVD used.