Search

Objective To compare the incidence of endophthalmitis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections with and without patient face masking. Design Two-centre retrospective cohort study Participants Patients receiving a total of 28 501 injections (period 1 before masking: n = 13 863; period 2 after masking: n = 14 638) Methods Periods before and after implementation of patient masking were compared: period 1 (July–December 2019) and period 2 (July–December 2020). All patients requiring treatment for endophthalmitis following intravitreal anti-VEGF injections were reviewed. Endophthalmitis risks were compared. Statistical simulations were run to determine the number of injections or endophthalmitis cases required to detect a statistically significant difference between both periods. Results Five patients (0.036%) had endophthalmitis in period 1 compared with 7 patients (0.048%) in period 2. Odds ratio, 95% confidence interval, for risk of patient masking was 1.326, 0.421–4.179 (p = 0.63). Three patients (0.022%) in period 1 had culture-positive endophthalmitis compared with 2 patients (0.014%) in period 2. Risk of patient masking for culture-positive endophthalmitis was 0.631, 0.105–3.779 (p = 0.61). Assuming similar rates of endophthalmitis, 476,806 injections in both groups would be required to detect a significant difference. Alternatively, assuming that masking would increase endophthalmitis risk in period 2, a significant difference would require twice as many cases (n = 15, 0.102%) for a risk of 2.843, 1.033–7.825 (p = 0.043). Conclusions The implementation of patient masking in clinical practice did not significantly alter the rate of endophthalmitis following intravitreal anti-VEGF injections.

We present a 65-year-old female smoker who presented with acute bilateral blurred vision. Investigations led to an endobronchial ultrasound-guided fine-needle aspiration resulting in an early diagnosis of limited stage small cell lung cancer. Positive recoverin antibodies supported the diagnosis of cancer-associated retinopathy (CAR). CAR was the first manifestation of systemic malignancy in our patient and early diagnosis enabled curative intent systemic treatment with chemotherapy and radiotherapy. Ocular-specific treatment is required in CAR, although no standardised treatment exists. Current treatment options include steroids and immunosuppressive agents. Our patient was administered bilateral intravitreal dexamethasone implants, resulting in significant visual field and electroretinogram improvement at 8 weeks post-intervention. To our knowledge, this represents the first reported successful use of intravitreal dexamethasone implants as first-line therapy, in conjunction with chemoradiotherapy. Intravitreal dexamethasone implants therefore may provide an effective and safe treatment for CAR by reducing intraocular inflammation without systemic effects.

Retinoblastoma is the most common intraocular tumour of the eye in children. It constitutes 11% of all cancers within the first year of life. In one-third of cases, it occurs bilaterally; usually, before 5 years of age without any gender predilection.[1 2][1] Trilateral retinoblastoma term is used

Purpose The authors describe a case of new bilateral epiretinal membranes and vitreous cells following intravitreal and subTenon's injections of bone marrow-derived stem cells. Methods Case report of a 43-year-old man with OPA-1 autosomal dominant optic atrophy who self-enrolled in a stem cell therapy clinical trial and received simultaneous bilateral intravitreal and subTenon's injections of bone marrow-derived stem cells. Results Within one month of receiving the injections, the patient developed epiretinal membranes and vitreous cells in both eyes, seen with optical coherence tomography. Conclusion Stem cell therapy has been gaining popularity as a potential intervention for progressive retinal and optic nerve diseases; however, the mechanism of action of bone marrow-derived stem cells is still not well understood and may result in unintended cell differentiation.

Purpose: To examine the effect of medication sample use (ranibizumab or aflibercept) on future anti-vascular endothelial growth factor (VEGF) agent selection in neovascular age-related macular degeneration (nvAMD). Design: Retrospective cohort study. Methods: nvAMD patients who underwent an initial anti-VEGF injection with a sample medication were compared to nvAMD control patients who never received a medication sample. Charts from 2017 through 2020 were reviewed for data regarding demographics, anti-VEGF agent selection, and visual acuity outcomes for both groups. Anti-VEGF agent selection for the first four injections and at one year were examined in both the sample and control groups. Results: Adherence to the initial agent was high between first and subsequent injections (2nd, 3rd, 4th injection, and 1 year) in both sample (96.2%, 95.9%, 91.9%, 93.4%, respectively) and control groups (98.1%, 94.2%, 94.9%, 87.8%, respectively). Bevacizumab usage was significantly lower among eyes receiving samples relative to controls at the second (1.9% vs. 38.7%, p

To report a case of nonleaking cystoid macular edema (CME) associated with pentosan polysulfate sodium (PPS)-induced pigmentary maculopathy.Multimodal imaging, including optical coherence tomography, fundus photography, autofluorescence, and fluorescein angiography, was used to substantiate our diagnosis, further characterize the cystoid macular edema showed by our patient and to monitor the response to treatment.A 59-year-old woman was referred for decreased visual acuity and bilateral macular edema. She had been treated for interstitial cystitis with PPS for 10 years. Multimodal imaging showed the characteristic features of PPS-induced pigmentary maculopathy. Moreover, fluorescein angiogram showed nonleaking cystoid macular edema in both eyes. She was treated successfully with intravitreal injections of bevacizumab.To our knowledge, this report is the first to demonstrate that PPS-associated cystoid macular edema can be nonleaking on fluorescein angiography and responds well to intravitreal anti-vascular endothelial growth factor injections.

To present a case of idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome that was successfully managed with serial intravitreal aflibercept injections.Ophthalmic imaging and visual acuity were used to monitor disease state and track treatment methods to determine the most valuable combination of treatment medication and treatment interval.A 28-year-old woman with idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome status after panretinal photocoagulation of both eyes presented with bilateral cystoid macular edema. We demonstrate successful management of retinal cystoid macular edema associated with idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome using serial intravitreal aflibercept injections.Intravitreal aflibercept has a useful role in managing the potential retinal complications associated with idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome and provides further insights into treatment of the later stages of this rare disease.

Purpose To report a case of Coccidioides immitis endophthalmitis with severe vision loss and a return to excellent vision following aggressive intervention. Methods Case report. Results A 41-year-old male with a history of solid organ transplantation who complained of floaters and decreased vision in the setting of disseminated Coccidioides infection was found to have presumed coccidioidal endophthalmitis with visual acuities (VA) of 20/20 in the right eye and 20/200 in the left eye. The patient was managed with intravenous amphotericin B, oral voriconazole, and intravitreal injections of amphotericin B and voriconazole in the left eye every three days. Five weeks after presentation, VA remained 20/20 in the right eye and improved to 20/40 in the left eye. The patient was transitioned to twice weekly intravitreal injections and oral voriconazole upon hospital discharge. One week later, vision in the left eye decreased to 20/500 with worsening vitritis, prompting vitrectomy. Vision in the left eye subsequently improved to 20/30. Five weeks later, the patient developed a macula-on inferior rhegmatogenous retinal detachment in the left eye and underwent a second vitrectomy, with scleral buckle, laser, and gas injection. Vision in the left eye returned to 20/25. In total, the patient received 22 amphotericin B and 17 voriconazole intravitreal injections in the left eye with two vitrectomies. Vision in the right eye remained 20/20 throughout his treatment course. At four months after presentation, the patient remained on oral voriconazole with no evidence of active intraocular infection on exam. Conclusions Aggressive medical and surgical management can be successful in ocular conservation and restoration of vision in coccidioidal endophthalmitis. Very mild disease may be conservatively monitored and managed with systemic antifungal therapy alone. In severe disease, early diagnosis and prompt and aggressive use of systemic and intravitreal antifungals may spare panophthalmitis and preserve vision.

Concomitant vitamin D deficiency (VDD) is speculated to aggravate diabetic macular edema (DME). We aimed to determine the effect of hypovitaminosis D correction on the outcome of treatment with intravitreal bevacizumab (IVB) in DME eyes.In this randomized clinical trial, 83 eyes of 83 patients with DME were recruited and divided into three groups: normal vitamin D levels + IVB administration (Group 1), vitamin D insufficient/deficient + IVB administration (Group 2), and vitamin D insufficient/deficient + IVB administration + oral vitamin D supplementation (Group 3). Participants were followed for 6 months after the intervention. Visual (corrected distance visual acuity, CDVA) and anatomical (central macular thickness, CMT) outcomes of intervention were evaluated 1, 3, and 6 months after three monthly loading doses of IVB were given. Serum vitamin D levels were measured 1 and 6 months after the third IVB administration.A total of 29, 26, and 28 eyes were enrolled in groups 1, 2, and 3, respectively. In months 1, 3, and 6, after the three basic loading doses of IVB, visual acuity and CMT improved in all three groups, but improvements (both functional and anatomical) in groups 1 and 3 in month 6 were more significant than in group 2 (mean CDVA LogMAR changes: - 0.18 ± 0.03, - 0.14 ± 0.05, and - 0.2 ± 0.06; mean CMT reductions: - 82.24 ± 11.43, - 66.62 ± 14.34, and - 86.14 ± 18.36, in groups 1, 2, and 3, respectively; p 0.001). The mean number of IVB injections during follow-up was 5.33 (range 4-7), which did not differ between the groups.Correction of vitamin D deficiency in DME patients with type 2 diabetes and vitamin D deficiency, in addition to IVB injections, may play a role in improving CDVA and CMT. However, this beneficial effect seems to be delayed by several months.Iranian Registry of Clinical Trials (IRCT), IRCT20200407046978N1, registered on April 11, 2020, retrospectively registered ( https://en.irct.ir/trial/46999 ).

PURPOSE: To investigate the cost-effectiveness of prophylactic treatments against cystoid macular edema (CME) after cataract surgery in diabetic patients.SETTING: Seven ophthalmology clinics in the Netherlands and Belgium.DESIGN: Prospective trial-based cost-effectiveness analysis using data from a European multicenter randomized clinical trial.METHODS: Diabetic patients (n=163) undergoing uncomplicated cataract surgery were randomized to perioperative subconjunctival triamcinolone acetonide (n=36), perioperative intravitreal bevacizumab (n=36), combination treatment (n=45), or no additional treatment (control group, n=46). The cost analysis was performed from a healthcare perspective within a 12-week postoperative time horizon. The main effectiveness outcome was quality-adjusted life years (QALYs). The main cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER; cost per QALY).RESULTS: Mean total healthcare costs and QALYs were: Triamcinolone € 1827 (US$ 2295) / 0.166; Bevacizumab € 2050 (US$ 2575) / 0.144; Combination € 2027 (US$ 2546) / 0.166; Control € 2041 (US$ 2564) / 0.156. Bevacizumab and control treatment were most costly and least effective. The ICER was € 321,984 (US$ 404,503) per QALY for the combination group compared to the triamcinolone group. Assuming the willingness-to-pay is € 20,000 (US$ 25,126) per QALY, the cost-effectiveness probability was 70% and 23% in the triamcinolone and combination groups, respectively. No patient that received triamcinolone developed clinically significant macular edema (CSME). A secondary cost-effectiveness analysis based on this outcome showed a clear preference for triamcinolone.CONCLUSIONS: In diabetic patients, subconjunctival triamcinolone was effective in preventing CSME after cataract surgery. The cost-effectiveness analysis showed triamcinolone is also cost-effective.

Ocriplasmin is used to treat vitreomacular traction (VMT), with or without full-thickness macular hole (MH). We systematically reviewed the evidence on ocriplasmin's effect on vitreomacular adhesion resolution (VMAR), MH closure, vitrectomy, and best-corrected visual acuity (BCVA) and investigated the effect of baseline covariates on outcome. We applied individual participant data meta-analyses to the entire population and to subgroups defined by MH or epiretinal membrane (ERM) presence. Safety data were pooled and tabulated. Five randomized controlled trials (1,067 participants) were included. Six months after treatment, ocriplasmin achieved higher rates of VMAR and MH closure versus control, lowered vitrectomy odds, and increased the likelihood of a ≥10-letter BCVA increase. VMAR rates were lower when ERM, broad VMA (> 1500 µm), diabetic retinopathy, or pseudophakia were present and higher in younger participants, women, and eyes with MHs. Ocriplasmin-treated participants experienced more short-term visual impairment that was not predictive of final BCVA, as well as vitreous floaters, photopsia, photophobia, eye pain, blurred vision, and dyschromatopsia. The most common serious adverse events for ocriplasmin and control, respectively, were MH progression (22.5%, 17.3%), new MH (1.5%, 3.4%) and retinal detachment (0.8%, 1.2%). Ocriplasmin promotes VMAR and MH closure. Transient visual phenomena are not uncommon.

PURPOSE To assess the relationship between best corrected visual acuity (BCVA) and central subfield optical coherence tomography (OCT) features in noninfectious uveitis (NIU)-related macular edema (ME). DESIGN Clinical cohort study from post hoc analysis of two phase 3 clinical trials' data. METHODS Correlation and longitudinal treatment analyses were performed. Of 198 patients with NIU, 134 received suprachoroidally administered CLS-TA (Clearside Biomedical, Inc. proprietary formulation of a triamcinolone acetonide injectable suspension) and 64 received sham, with 12.9% and 72% respectively receiving rescue therapy. RESULTS At baseline, mean BCVA progressively worsened with each ordinal drop in ellipsoid zone (EZ) integrity. Eyes with normal baseline EZ experienced greater 24-week change in BCVA compared to eyes with some degree of baseline EZ disruption (11.9 vs 9.4 letters, P=0.006). In contrast, eyes without central subfield cystoid spaces and/or central subfield SRF at baseline showed less improvement (5.5 letters or 9.5 letters, respectively) at 24 weeks, compared to those eyes with such OCT findings (13.7 letters, P = 0.012 or 17.2 letter, P

Purpose To assess morphological changes and visual results in eyes with pachychoroid neovasculopathy (PNV) that underwent different intravitreal anti-vascular endothelial growth factor (VEGF) agents. Materials and methods This is a retrospective, observational, comparative study that included 76 PNV eyes in 76 patients that were allocated to three groups according to the monotherapy injection procedure, as follows: the intravitreal bevacizumab (IVB) group, intravitreal ranibizumab (IVR) group, and intravitreal aflibercept (IVA) group. Central macular thickness (CMT), best-corrected visual acuity (BCVA), and subfoveal choroidal thickness (SFCT) were measured at baseline, after treatment 1st month, 3rd month, 6th month, and 12th month, and at the final post-treatment examination. Results Mean age of the patients was 57.31 +/- 5.91 years (range: 34-67 years). The mean duration of follow-up was 31.50 +/- 12.91 months (range: 13-60 months). The IVB group included 30 eyes, the IVR group included 22 eyes, and the IVA group included 24 eyes. There weren\"t any significant differences in BCVA changes between the groups at any post-baseline measurement time point. Although CMT did not change significantly in the IVB group from baseline to the final follow-up visit (baseline: 376.33 +/- 86.31 mu m; final visit: 340.80 +/- 122.70 mu m) (p = 0.172), CMT did change significantly in the IVA group (baseline: 383.41 +/- 131.83 mu m; final visit: 297.33 +/- 103.81 mu m) (p = 0.029) and IVR group (baseline: 379.18 +/- 97.93 mu m; final visit: 335.72 +/- 111.45 mu m) (p = 0.041). SFCT decreased significantly in the IVR and IVA groups (p = 0.015 and p < 0.001, respectively). The mean number of injections was 12.06 +/- 4.72 (range: 6-20) in the IVB group, 11.81 +/- 3.31(range: 7-17) in the IVR group, and 7.16 +/- 3.15 (range: 4-13) in the IVA group (p = 0.004). Conclusion All three anti-VEGFs were effective in terms of visual results in patients with PNV. Patients treated with IVA required fewer injections than those treated with IVB or IVR. Furthermore, IVR and IVA treatment significantly decreased SFCT, whereas IVB did not.

To compare visual outcome and recurrence rates of eyes with noninfectious inflammatory choroidal neovascularization (CNV) treated with or without anti-vascular endothelial growth factor (VEGF) injections and immunosuppression.Retrospective, nonrandomized clinical study.Participants: Patients with CNV secondary to noninfectious inflammatory causes who attended uveitis clinics at Moorfields Eye Hospital between January 2000 and April 2016. Data were gathered from the clinical notes of all subjects examined in clinic.change in best-corrected visual acuity (BCVA), mean time to CNV recurrence, moderate vision loss (≤20/50), and severe vision loss (≤20/200).A total of 166 patients (204 eyes) with noninfectious inflammatory CNV were included in this study with a median follow-up of 6.9 years (interquartile range: 2.9-11.7; 1652 eye-years). The mean BCVA at the time of CNV diagnosis was 0.38 ± 0.05 logarithm of the minimum angle of resolution (logMAR) (Snellen equivalent 20/47) in the eyes that received the first-line anti-VEGF treatment and 0.44 ± 0.03 logMAR (Snellen equivalent 20/55) in the eyes on other treatment modalities (P = .39). Eyes treated first with anti-VEGF (n = 55) received the mean of 4.35 ± 0.53 injections and showed a statistically significant improvement in vision at all time points (P.001) except for a 5-year visit (P = .25). The rest of the eyes demonstrated no significant change in vision throughout follow-up (all P.05). At the final visit, the mean BCVA was 0.26 ± 0.11 logMAR (Snellen equivalent 20/36) in the former and 0.35 ± 0.06 logMAR (Snellen equivalent 20/44) in the latter. The mean time to CNV recurrence was 186 ± 15.1 months, and the risk was significantly reduced by treatment with oral corticosteroids (adjusted hazard ratio = 0.32, confidence interval: 0.17-0.59, P.001) or anti-VEGF injections (adjusted hazard ratio = 0.31, confidence interval: 0.18-0.52, P.001).Eyes that developed inflammatory CNV were at risk of vision loss. Those receiving early anti-VEGF injections achieved a better visual outcome and had a reduced risk of CNV recurrence. Oral corticosteroids also had an effect that reduces the risk of recurrence in eyes previously treated.

Purpose Determine associations between early residual fluid (ERF)-free status and improved long-term visual outcomes. Design Clinical cohort study from post hoc analysis of two phase 3 clinical trials’ data. Methods Independent of treatment allocation, patients from the multicenter, prospective, randomized, double-masked HAWK and HARRIER trials who received either brolucizumab 6 mg or aflibercept 2 mg were split into two cohorts dependent on presence or absence of ERF at week 12. Additionally, similar analyses were performed on presence or absence of early residual intraretinal fluid (IRF) and subretinal fluid (SRF) at week 12. The two groups, ERF-free (N=1051) and ERF (N=366) were compared. Changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were determined. Results From week 12 to 96, patients who were ERF-free had greater least square (LS) mean increases from baseline for BCVA and CST compared to ERF patients. Greater LS mean differences in BCVA from week 12 to 96 were noted between ERF-free and ERF patients. A greater proportion of patients in the ERF-free cohort reported a ≥5, ≥10, or ≥15 letter improvement and a higher proportion reported BCVA ≥70 letters from baseline to week 96 compared to those with fluid. Conclusions Improvements in visual outcomes in ERF-free patients were greater than in ERF patients occurring as early as 4 weeks (week 12) following the last loading dose and continued to week 96. Therefore, ERF status may be a useful indicator of anti-vascular endothelial growth factor treatment response.

To describe clinical and ophthalmologic features and outcomes of patients with coronavirus disease-19 with retinal vascular occlusions.Retrospective multicenter case series and PubMed review of cases reported from March 2020 to September 2021. Outcome measures are as follows: type of occlusion, treatments, best-corrected visual acuity, and central macular thickness on optical coherence tomography.Thirty-nine patients were identified. Fifteen patients with a median age of 39 (30-67) years were included in the multicenter study. Vascular occlusions included central retinal vein occlusion (12 eyes), branch retinal vein occlusion (4 eyes), and central retinal artery occlusion (2 eyes). Three cases were bilateral. Baseline best-corrected visual acuity was 20/45 (no light perception-20/20). Baseline central macular thickness was 348.64 (±83) μm. Nine eyes received anti-vascular endothelial growth factor agents, dexamethasone intravitreal implant, or both. Final best-corrected visual acuity was 20/25 (no light perception-20/20), and central macular thickness was 273.7 ± 68 μm (follow-up of 19.6 ± 6 weeks). Among the 24 cases from the literature review, retinal vein occlusion was the predominant lesion. Clinical characteristics and outcomes were similar to those found in our series.Coronavirus disease-19-associated retinal vascular occlusions tend to occur in individuals younger than 60 years. Retinal vein occlusion is the most frequent occlusive event, and outcomes are favorable in most cases.

Purpose To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential. Design Multicenter, open-label, single- and multiple-dose phase 1 study. Methods Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm2 and best-corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, 15 mg) or received 2 doses NGM621 15 mg 4 weeks apart in the multidose phase and were followed for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments. Results All 15 participants completed the 12-week study. There were no serious adverse events and no drug-related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points. Conclusions In this small, open-labelled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg.

PURPOSE To compare outcomes of glaucoma drainage device (GDD) implantation and trabeculectomies with and without postoperative intravitreal injections (IVIs) in glaucoma patients with a history of preoperative IVIs. DESIGN Retrospective cohort study. PARTICIPANTS A total of 133 eyes of 133 glaucoma patients who underwent GDD implantation or trabeculectomy with at least 1 IVI preoperatively between January 2005 and October 2020 at Massachusetts Eye and Ear. METHODS Chart review of glaucoma patients with traditional glaucoma surgery and at least 1 IVI before surgery. All statistical analyses were conducted with R statistical programming software. MAIN OUTCOME MEASURES Intraocular pressure (IOP), medication burden, best-corrected visual acuity (BCVA), Kaplan-Meier success rates, adjusted hazard ratios (HRs), and complications. RESULTS Baseline demographics were similar between the groups with and without postoperative IVIs. The group with postoperative IVIs had a higher proportion of diabetic retinopathy and retinal vascular occlusions than the group without postoperative IVIs, which had more eyes with age-related macular degeneration. Intraocular pressure, medication burden, and visual acuity were similar between groups at all time points except for IOP at 6 weeks, which was lower in the group with postoperative IVIs. The group with postoperative IVIs had significantly more preoperative IVIs than the group without postoperative IVIs (6.6 vs. 3.3, P = 0.017). For success defined as IOP reduction ≥ 20% with 5 < IOP ≤ 21 mmHg, Kaplan-Meier analyses demonstrated similar success rates between groups with and without IVIs. When stratified by the number of IVIs, success rates for the group with 7 or more IVIs were significantly higher than the success rates for the group with 0-6 IVIs (P = 0.005). Each additional postoperative IVI resulted in a 7.2% decrease in the hazard of failure to achieve our stated success criteria. With regard to late complications, the group with postoperative IVIs had a higher incidence of vitreous hemorrhage (18.5% vs. 3.2%, P = 0.039) than the group without postoperative IVIs. CONCLUSIONS A higher number of postoperative IVIs, specifically 7 or more IVIs, may be associated with improved success rates of traditional glaucoma surgery in glaucoma patients who received IVIs before surgery.

Widefield swept-source optical coherence tomography (OCT) imaging was used to characterize choroidal thickness and vascularity at baseline in proliferative diabetic retinopathy (PDR) and longitudinally after panretinal photocoagulation (PRP).Patients with treatment-naive PDR were imaged at baseline and at 1 week, 1 month, and 3 months after PRP. Previously validated algorithms were used to calculate the mean choroidal thickness (MCT) and choroidal vascularity index (CVI) in 5 regions of 12 mm × 12 mm scans.Fourteen PDR eyes were included. Baseline MCT in PDR eyes did not differ significantly from normal eyes, but CVI measurements in PDR eyes were lower in all regions (P0.001-0.008). After PRP, MCT measurements in PDR eyes were significantly lower at 1 month and 3 months in all regions (P0.001-0.005) except the fovea (P = 0.074). However, CVI measurements did not change over time in any region after PRP.The choroid in PDR eyes has a smaller CVI than that in normal eyes. After PRP, the choroidal thickness decreases outside the fovea, but the CVI remains constant, which suggests that a relative decrease in choroidal vascularity persists. These widefield swept-source OCT results are consistent with choroidal alterations found in histopathological reports of diabetic choroidopathy.

Purpose To present a case of endophthalmitis caused by Abiotrophia defectiva after repeated injections of dexamethasone intravitreal implant (Ozurdex), in a patient already on systemic immunosuppressive therapy, and discuss the management of this challenging situation. Methods Case report and review of literature. Results A 70-year-old female patient with history of idiopathic pulmonary fibrosis presented for urgent evaluation due to left eye vision loss and mild discomfort 12 days after receiving her seventh dexamethasone implant injection. Ocular history was pertinent for recurrent macular edema resulting from a remote branch vein occlusion. Twelve days after her last injection, visual acuity decreased from 20/30 to counting fingers at 5 feet. Slit-lamp examination showed anterior chamber cell without fibrinoid membranes or hypopyon. Within hours, the patient's clinical appearance progressed. A vitreous tap followed by intravitreal injection of vancomycin (1 mg/0.1 mL) and ceftazidime (2.25 mg/0.1 mL) was performed. The culture from the vitreous sample revealed heavy growth of A. defectiva. Owing to limited improvement, patient was taken to the operating room, and the presence of a full-thickness scleral defect at the site of most recent dexamethasone implant injection was confirmed. Vitrectomy with removal of implant, closure of all sclerotomies, including nonhealing full-thickness scleral defect, and repeated intravitreal antibiotic injection were performed. At the 3-month follow-up, no inflammation was observed, but visual acuity remained poor. Conclusion Intravitreal dexamethasone implant-associated endophthalmitis in the setting of systemic immunosuppression is a rare and challenging situation. Both local and systemic immunosuppression may delay wound healing, predisposing to wound leakage and consequent endophthalmitis. Despite repeated intravitreal antimicrobial injection and vitrectomy with implant removal, A. defectiva endophthalmitis carried a poor visual outcome.

Purpose Endophthalmitis following intravitreal anti-VEGF injections is frequently caused by Streptococcus viridans organisms and tends to be aggressive. Herein we present a case of post-injection Streptococcus viridans endophthalmitis presenting in an atypically delayed fashion with good visual outcome. Methods Single clinical case report. Patients A 91-year-old female treated with Aflibercept for exudative age-related macular degeneration of the left eye presented to the emergency department with mild pain and visual acuity decline to counting fingers, pigmented anterior chamber cells and vitreous haze 7 weeks after her most recent intravitreal injection. She had no symptoms of systemic infection. The presumptive diagnosis initially was vitreous haemorrhage. Results Over 10 days of observation, she developed worsening pain and vitritis suggestive of endophthalmitis, leading us to perform vitrectomy with intravitreal Vancomycin and Ceftazidime. Vitreous biopsy was culture positive for Streptococcus intermedius, a type of viridans streptococcus typically associated with head and neck abscesses. The infection resolved and the patient's visual acuity returned to her baseline of 20/100, with no recurrence of infection after four months of follow-up DISCUSSION:: The virulence of viridans streptococci capable of producing post-injection endophthalmitis may vary widely. Infection ought to be suspected even in cases of delayed onset intraocular inflammation.

PURPOSE We describe a case of endophthalmitis caused by streptococcus salivarius presenting as a retinal vasculitis less than twenty-four hours after intravitreal injection. METHODS Case report RESULTS:: The patient progressed from a hemorrhagic retinal vasculitis to severe endophthalmitis with no view to the posterior segment within 24 hours. Visual acuity progressed from 20/20 pre-injection to light perception within less than 48 after injection. Vitreous tap and injection was performed within 24 hours of intravitreal aflibercept injection, followed by pars plana vitrectomy the next day. Final visual acuity was hand motions. CONCLUSIONS Streptococcus salivarius is a virulent organism that may cause an endophthalmitis early after intravitreal injection with an unusual presentation of hemorrhagic retinal vasculitis. A high index of suspicion for infectious endophthalmitis should be maintained for all patients presenting with ocular inflammation and worsening vision in the days following intravitreal injections.

To describe the occurrence of full-thickness macular hole formation and spontaneous closure in a case of central retinal vein occlusion treated with intravitreal ranibizumab.A 67-year-old hypertensive man presented with acute central retinal vein occlusion with macular edema in his left eye for which he received intravitreal ranibizumab.He developed a FTMH following the second injection, which was kept under observation. Recurrence of intraretinal edema allowed approximation of the MH edges which subsequently achieved closure with further intravitreal RBZ and formation of an epiretinal membrane.Full-thickness macular hole formation in acute central retinal vein occlusion after intravitreal ranibizumab, although rare, can occur in eyes with massive macular edema and absence of posterior vitreous detachment after intravitreal pharmacotherapy. Spontaneous closure of secondary holes can take place with improvement in visual acuity.

To report the clinical course and treatment outcomes of a patient with central retinal vein occlusion with severe macular edema in early pregnancy.Interventional case report.A 39-year-old woman with gestational diabetes mellitus and a 15-pack year smoking history presented at 7 weeks gestation with decreased vision due to central retinal vein occlusion with marked macular edema. One month later, visual acuity had decreased to 20/400, and macular edema had worsened to a central subfield thickness of 1,432 μ m. She was treated with a single intravitreal dexamethasone implant at 16 weeks gestation. She responded well with visual acuity improving to 20/40+ and complete resolution of macular edema. At 33 weeks gestation, the cystoid macular edema recurred, but the patient refused treatment. The cystoid macular edema spontaneously resolved 3 weeks postpartum but recurred 3 months later with visual acuity worsening to 20/50. This macular edema resolved completely after a single 1.25 mg bevacizumab injection. She required no further treatment, and 23 months later, her macula was dry with visual acuity of 20/25. Her baby was healthy.Although pregnancy seems to aggravate central retinal vein occlusion -associated macular edema, the visual loss may be reversible. Intravitreal steroid seems to be effective during pregnancy with no apparent systemic or fetal complications. Young patients with retinal vein occlusion and center-involving macular edema may stabilize with minimal treatment.

Purpose This analysis of the pivotal phase 3 HAWK and HARRIER trials aimed to provide insights on the timing of presentation, management, and outcomes of intraocular inflammation (IOI)-related adverse events (AEs), as reported by investigators in these trials. Design Post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER. Participants Of 1088 brolucizumab-treated eyes (3 or 6 mg), 49 eyes demonstrated at least 1 IOI-related AE and were included in this analysis. Methods Reports of IOI-related AEs were analyzed and descriptive statistics were provided for outcome measures. Main Outcome Measures Incidence and description of eyes with IOI-related AEs, timing of presentation, management, clinical outcomes, and brolucizumab treatment after the first IOI-related AE. Results Seventy IOI-related AEs were reported in 49 eyes. Before the onset of first IOI-related AE, eyes received a mean ± standard deviation (SD) of 3.9 ± 2.2 brolucizumab injections. Median time to first IOI-related AE from the last administered brolucizumab injection was 18.0 days (interquartile range, 4.0–29.0 days). Of the 70 AEs, 61 (87.1%) were treated, most with topical corticosteroids; systemic and intraocular corticosteroids were used for 3 AEs each. Overall, inflammation resolved completely in 39 eyes (79.6%), resolved with sequelae in 5 eyes (10.2%), and did not resolve in 5 eyes (10.2%) by end-of-study (EOS). Overall, the mean ± SD best-corrected visual acuity (BCVA) change from baseline to EOS, before AE to the lowest BCVA in 3 months after AE, and from before AE to EOS were −0.84 ± 20.6 , −16.31 ± 17.6, and −0.22 ± 18.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively. Of the 36 eyes (73.5%) that continued with brolucizumab therapy after the first IOI-related AE, 24 completed the trials and 12 discontinued; mean ± SD BCVA change in these eyes was 2.6 ± 17.6, 7.8 ± 13.2, and −7.7 ± 21.3 ETDRS letters, respectively, from baseline to EOS. The remaining 13 eyes (26.5%) were not treated with brolucizumab after first IOI-related AE and showed a mean ± SD BCVA change of −10.4 ± 25.5 ETDRS letters from baseline to EOS. Conclusions Findings of this analysis highlight the need for continued vigilance and monitoring for any signs of IOI-related events in patients receiving brolucizumab.

Purpose To evaluate early predictive factors of visual loss in patients treated with anti–vascular endothelial growth factor (VEGF) injections under an as-needed regimen for neovascular age-related macular degeneration (AMD). Design Post hoc analysis from the randomized controlled trial Groupe d’Evaluation Francais Avastin versus Lucentis (GEFAL). Participants A total of 393 patients with neovascular AMD. Methods The present analysis is based on 1-year data from patients included in the study. Patients were separately categorized according to the best-corrected visual acuity (BCVA) change at 3 months and 1 year into 3 trajectories: (1) patients with no vision loss ≥5 letters at 3 months and 1 year (absence of loss ≥5 letters); (2) patients with no vision loss ≥5 letters at 3 months but loss ≥5 letters at 1 year (secondary loss ≥5 letters); and (3) patients with vision loss ≥5 letters at 3 months and 1 year (initial loss ≥5 letters). Main Outcome Measures The following factors were evaluated at baseline and 3 months: age, sex, BCVA, presence of fluid, central macular thickness, angiographic choroidal neovascularization (CNV) subtype, CNV area measured in disc area on fluorescein angiography, and number of intravitreal injections. Results An absence of loss ≥5 letters was found in 225 patients (57.3%), a secondary loss ≥5 letters after 3 months was found in 109 patients (27.7%), and an initial loss ≥5 letters was found in 59 patients (15%). Baseline characteristics were comparable among the 3 groups except for the total CNV area, which was larger in the initial and secondary loss groups (P = 0.0412). At 3 months, a significant association was found between presence of subretinal fluid (SRF) (P = 0.0318) and vision loss ≥5 letters, and an even stronger significant association between the presence of intraretinal fluid (IRF) (P = 0.0066) and vision loss ≥5 letters. Conclusions In the present study, we found that a large CNV area at baseline was significantly associated with initial or secondary loss of visual acuity ≥5 letters despite anti-VEGF injection. The presence of fluid, both SRF and IRF, at 3 months was found in patients with poorer trajectories.

To determine the long-term cognitive outcomes in children who underwent intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP).Prospective cohort study.This single-center study enrolled 186 children between 3 and 6 years of age and included 101 children in the final analysis: premature without ROP (group 1), ROP not needing treatment (group 2), IVB monotherapy (group 3), IVB plus laser therapy (group 4), and laser monotherapy (group 5). The Full-Scale Intelligence Quotient (FSIQ) was evaluated by the Wechsler Preschool and Primary Scale of Intelligence Test at baseline and then annually for 1-2 years and compared among groups.The age at cognitive evaluation was 4.5-4.9 years at baseline and 6.1-7.0 years at the last follow-up. The FSIQ was comparable among the groups at both time points (P = .08 and .50, respectively). Severe cognitive impairment (FSIQ70) was more common in group 4 at baseline (4%, 22%, 13%, 33%, and 0% in groups 1-5, respectively; P = .03) but did not differ among the groups at the last follow-up (6%, 0%, 4%, 22%, and 0%; P = .22). After adjusting for sex, Apgar score, neonatal adverse events, and days on mechanical ventilation, IVB was not associated with FSIQ either at baseline or at the last follow-up.At 4.5 to beyond 6 years of age, children who underwent IVB monotherapy had comparable cognitive outcomes compared to the other premature children without prior IVB. Children who underwent IVB plus laser showed higher severe cognitive impairment at 4.5 years of age.

Introduction To evaluate the effects of combined therapy using intravitreal Aflibercept (IVA) and photodynamic therapy (PDT) on polypoidal choroidal vasculopathy related to pachychoroid disease (PPCV).Methods Patients with PPCV were treated with PDT combined with 3 IVA injections on a monthly basis, followed by pro re nata criteria. The 12-month follow-up consisted of multiple revaluations of visual acuity and SSOCT parameters of clinical activity.Results Nineteen eyes were included in the study; mean age was 65.5 years. Visual acuity improved after 12 months (0.35 ± 0.25 to 0.2 ± 0.20 logMAR, p = 0.005). Percentage of eyes with intraretinal and subretinal fluid reduced from baseline to the 12-month follow-up (from 52.6–10.5%, p = 0.12, and from 89.5–5.3% p = 0.0009, respectively). Central retinal and mean macular thicknesses reduced (258 ± 39.6 to 204.8 ± 38.8 µm p = 0.04 and 293.8 ± 32.1 to 248.1 ± 29.6 µm p = 0.017 respectively). Central choroidal and mean choroidal thicknesses also displayed a reduction (328.6 ± 54.9 to 289.8 ± 44.6 µm p = 0.001 and 314.5 ± 55.3 to 287.9 ± 47.6 µm p = 0.015 respectively). The mean number of injections was 4.6/year.Conclusion The results support the use of a combined therapy with Aflibercept and PDT in PPCV. This treatment would act in synergy, with anti-VEGF controlling exudation and PDT closing the aneurysmal vessel and reducing choroidal congestion.

Anti-vascular endothelial growth factor (VEGF) therapy is used to slow the disease progression of neovascular age-related macular degeneration. Due to the treatment burden of frequent intravitreal injections, anti-VEGFs are often used on treat and extend protocols rather than the labeled frequency. The current goal of anti-VEGF drug development is to minimize treatment burden by reducing the number of intravitreal injections. The purpose of this systemic review and model-based meta-analysis (MBMA) was to (1) perform modeling to describe the disease progression of neovascular age-related macular degeneration in the absence of treatment, as well as in the presence of abicipar, aflibercept, brolucizumab, or ranibizumab intervention; (2) and to simulate virtual head-to-head comparisons among the drugs with an extended dose schedule of once every 12 weeks (Q12). Data sources were PubMed, internal Allergan data, www.clinicaltrials.gov, and www.clinicaltrialsregister.eu. Eligibility assessment was performed by 2 independent review authors. Randomized, controlled trials that had at least 1 arm with an anti-VEGF (aflibercept, abicipar, bevacizumab, brolucizumab, pegaptanib, or ranibizumab), a control arm of placebo or anti-VEGF, a treatment duration of at least 4 months, reported best-corrected visual acuity data, and at least 20 patients were included. A total of 22 trials, consisting of 55 arms, from across 9500+ subjects and 500+ best-corrected visual acuity observations were used to develop the model. Consistent with reported data, results from the model showed that abicipar Q12 underperformed ranibizumab (every 4 weeks), aflibercept (every 4 weeks), and brolucizumab (every 8 weeks/Q12) labeled dosing schedules. However, when all drugs were virtually tested using the extended schedule, abicipar outperformed ranibizumab and aflibercept and produced a similar week 52 change from baseline as brolucizumab. Predicted week 52 changes from baseline were 5.92 ± 1.02, 3.04 ± 1.61, 6.61 ± 0.284, and 3.02 ± 2.35 best-corrected visual acuity letters for abicipar, aflibercept, brolucizumab, and ranibizumab, respectively, using the Q12 schedule. Results demonstrate the feasibility of Q12 dosing with clinically meaningful letter gains for abicipar and brolucizumab. The model developed under this MBMA has utility for exploring different regimens for existing or novel anti-VEGF agents.

Purpose This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD). Design This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study. Participants A total of 477 patients were randomly assigned to receive FYB201 (n = 238) or reference ranibizumab (n = 239). Methods Patients received FYB201 or ranibizumab 0.5 mg by intravitreal injection in the study eye every four weeks. Main Outcome Measures The primary end point was change from baseline in best corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks prior to the third monthly intravitreal injection. Biosimilarity of FYB201 to its originator was assessed via a two-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters. Results BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was –0.4 ETDRS letters with a 90% confidence interval (CI) of –1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups. Conclusions FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD.

Purpose : To evaluate the effect of loss to follow up (LTFU) on outcomes in eyes with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (VEGF). Design : Retrospective cohort study Methods : Single-center study of 90 eyes of 73 patients with non-proliferative diabetic retinopathy (NPDR) and DME treated with anti-VEGF injections who were LTFU for >6 months. Main outcomes were the change in mean visual acuity (VA) and central foveal thickness (CFT) at the return and final visits compared to the visit before LTFU. Results : Mean age was 64.5 years, mean LTFU duration was 322 days, and mean follow-up duration after return was 502 days. Compared to the mean VA at the visit before LTFU (0.42, Snellen ∼20/52), mean VA worsened at the return visit (0.54, Snellen ∼20/69, p=0.004). No significant change in the mean VA was noted at the 3-month after return visit (0.50, Snellen ∼20/63), the 6-month after return visit (0.46, Snellen ∼20/57), the 12-month after return visit (0.42, Snellen ∼20/52) and the final follow up (0.47, Snellen ∼20/59). When analyzed by NPDR severity before LTFU, no difference in VA was found from the visit before LTFU to the final visit. Mean CFT increased when comparing the visit before LTFU (270 μm) to the return visit (305 μm, p=0.012), but no difference was found by the final visit [247 μm, p=0.07]. Conclusions : Anti-VEGF treated DME patients who were LTFU for a prolonged period experienced a modest decline in VA that recovered after restarting treatment.

Background/purpose To investigate the clinical characteristics of intraocular lymphoma and to evaluate two protocols of intravitreal methotrexate injection. Methods A retrospective chart review was conducted of newly-diagnosed intraocular lymphoma patients between January 2013 and January 2018 at National Taiwan University Hospital. Patients were divided into two groups. In Group A, intravitreal methotrexate was administered weekly for the initial 8 weeks, every 2 weeks for the following 12 weeks, and then monthly for 7 months. In Group B, intravitreal methotrexate was administered twice a week for the initial 2 weeks, weekly for the subsequent 2 weeks, once every 2 weeks for the next 1 month, and monthly for the last 10 months. Results A total of 12 patients were analyzed in the study; seven of these patients were allocated to Group A. Differences in the overall survival and progression-free survival between the two groups did not yield statistical significance. The median visual acuity was improved from LogMAR 0.46 to LogMAR 0.30 with borderline significance in Group A (p = 0.053). Two of seven patients in Group A and five of five patients in Group B developed punctate keratitis during intravitreal methotrexate injection treatment. Conclusion Intravitreal methotrexate is an effective and repeatable treatment for intraocular lymphoma. A new protocol with reduced frequency of intravitreal injections as shown in this study could potentially produce similar results without a worse prognosis, along with a decrease in the incidence of keratitis.

PURPOSE To investigate the recurrence rate of active macular neovascularization in patients with neovascular age-related macular degeneration (nAMD) previously followed up in a treat-and-extend (TE) regimen in which treatment had been stopped because of disease stability. DESIGN Prospective cohort study. PARTICIPANTS One hundred five patients with nAMD previously followed up in a TE regimen treated with aflibercept injections. METHODS All patients with a dry macula on 3 consecutive visits 12 weeks apart were eligible to participate in the study. Patients were examined at baseline and then monitored for disease recurrence 4, 6, 8, 10, and 12 months after the last injection. MAIN OUTCOME MEASURES The proportion of patients with recurrent disease within 12 months after the last injection. Change in best-corrected visual acuity (BCVA) at the time of recurrence and after resumed therapy. RESULTS Evidence of recurrent nAMD was seen in 54 of 102 patients (52.9%) after 12 months of follow-up. The mean time to recurrence after the last injection was 6.7 ± 2.2 months. The BCVA decreased from 71.7 ± 10.0 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 68.1 ± 11.1 ETDRS letters at the recurrence (P = 0.12). After treatment resumed, BCVA increased to 71.4 ± 10.0 ETDRS letters (P = not significant compared with baseline). Patients with a pigment epithelial detachment (PED) at baseline showed a 74% (14/19) recurrence rate compared with 48% (40/83) in patients without a PED (P < 0.05). Only 22 of 54 patients (40.7%) with recurrent disease showed symptoms of visual loss or metamorphopsia. CONCLUSIONS Recurrent nAMD is common in previously stable patients for whom anti-VEGF injections have been suspended. It is difficult to predict which patients will experience a recurrence, and most of these patients do not show symptoms in the early stages of reactivation. Long-term follow-up is important, and early detection of recurrent disease can improve the chances for maintained visual function.

Objectives: This study aimed to retrospectively evaluate the intraocular pressure (IOP) change in vitrectomized and non-vitrectomized patients receiving 0.7 mg intravitreal dexamethasone implant to treat macular edema due to different indications. Materials and Methods: The patients’ diagnoses, IOP values before receiving the intravitreal dexamethasone implant and in follow-up examinations at 1-3 days, 1 month, 2 months, 3 months, 6 months, 9 months, and 12 months after implantation, pachymetry values, medications used, and history of vitrectomy surgery were recorded. Results: A total of 134 eyes of 112 patients between 46 and 85 years of age who received intravitreal dexamethasone implants were evaluated. Seventeen eyes (12.7%) were vitrectomized and 117 (87.3%) were not vitrectomized. In non-vitrectomized eyes, the mean IOP was 14.01±2.36 mmHg before and 14.8±2.96 at 1-3 days, 16.71±3.97 at 1 month, 17.88±5.27 at 2 months, 15.54±3.35 at 3 months, 15.1±3.24 at 6 months, and 14.61±3.71 mmHg at 12 months after receiving the first dose. In this group, the increases in mean IOP at 1-3 days, 1 month, 2 months, and 3 months were significant compared to the mean IOP before the first dose (p

The primary objective was to create and establish a new formula that predicts the individual probability of macular hole closure for eyes with full thickness macular holes (FTMH) accompanied by vitreomacular traction (VMT) which received enzymatic vitreolysis using intravitreally administered ocriplasmin. The secondary objective was to evaluate the forecast reliability of a previously published formula for VMT resolution in VMT-only eyes (OddsIVO-Success = eIntercept × ORyears × ORln(µm); ProbabilityIVO-Success = OddsIVO-Success/(OddsIVO-Success + 1)) on VMT resolution using the current dataset of eyes with FTMH accompanied by VMT. Retrospective analysis of the OASIS, ORBIT, and INJECT-studies. Patients with FTMH and VMT with complete information (n = 213) were included. The effect of gender, age, FTMH diameter, lens status and the presence of epiretinal membranes (ERM) on FTMH closure was assessed using separate univariate logistic regression analyses. With regard to VMT release separate univariate regression analyses were carried out and results were compared with formerly published data of VMT resolution in eyes with VMT only. Overall, 126 eyes (63%) experienced VMT resolution within 28 days. Younger age (p