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Purpose: To assess the impact of intravitreal injections (IVTI) on ocular surface of patients treated with multiple injections., Methods: Prospective, tricentric study conducted in patients treated with unilateral IVTI. An asepsis protocol with povidone-iodine was used for all patients during IVTI. The primary endpoint was the difference between the pre-IVTI Ocular Surface Disease Index (OSDI 1) score and that measured on day one (D1) post-IVTI (OSDI 2). Secondary endpoints were the evaluation of predictive factors for OSDI scores, pain assessment on D1, and the Lacrydiag® analysis of tears from the injected eye versus contralateral eye before IVTI., Results: Two hundred and nineteen patients with a mean age of 75.9 ± 10 years were included. The mean OSDI2-OSDI1 difference was 19.2 ± 20.6 (p < 0.001). The mean noninvasive tear break-up time was 6.41 ± 4.59 seconds in the injected eye versus 7.36 ± 4.36 seconds in the contralateral eye (p < 0.001). In the multivariate analysis, the factors significantly associated with the OSDI 2 score were the OSDI 1 score (p < 0.001), the pain score on D1 (p < 0.001) the number of instilled glaucoma eye drop (p = 0.01) and a centre effect (centres 2 and 3 versus centre 1, p < 0.001)., Conclusion: Our results confirm the impairment of the ocular surface and quality of life immediately after an IVTI. These results suggest 3 levels of action to improve the immediate tolerance: improving the basal status of the ocular surface, reducing the contact time with povidone-iodine that might be toxic to the surface, and improving immediate post-IVTI treatment., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Pathological angiogenesis is the hallmark of many vision-threatening diseases. Anti-VEGF is a primary treatment with substantial beneficial effects. However, such agents require frequent intravitreal injections. Our previous work established a method for effectively modifying exosomes (EXOs) for loading therapeutic peptides. Here, we used this system to load the anti-angiogenic peptide KV11, aiming to establish an EXO-based therapy strategy to suppress neovascularization in the retina. Methods: Using an anchoring peptide, CP05, we linked KV11 to endothelial cell (EC) derived EXOs, yielding EXO KV11 . We tested the delivery efficiency of EXO KV11 via two commonly used ocular injection methods: retro-orbital injection and intravitreal injection. Deploying an oxygen-induced retinopathy (OIR) model and a VEGF injection model, we tested the effects of EXO KV11 on neovascular formation, EC proliferation, and vascular permeability. In vitro experiments were used to test the mechanism and to analyze the effects of EXO KV11 on EC proliferation, migration, and sprouting. Results : By using the EXO loading system, KV11 was more efficiently delivered to the blood vessels of the mouse retina via retro-orbital injection. In both OIR model and VEGF injection model, EXO KV11 was more effective than KV11 alone in inhibiting neovascularization and vessel leakage. The therapeutic effect of retro-orbital injection of EXO KV11 was comparable to the intravitreal injection of VEGF-trap. Mechanistically, KV11 alone inhibited VEGF-downstream signaling, while EXO KV11 showed a stronger effect. Conclusions: We used EXOs as a carrier for intraocular delivery of KV11. We showed that KV11 itself has an anti-angiogenic effect through retro-orbital injection, but that this effect was greatly enhanced when delivered with EXOs. Thus, this system has the potential to treat proliferative retinopathy via retro-orbital injection which is a less invasive manner compared with intravitreal injection., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

To evaluate the effects of intravitreal ranibizumab injection (IVR) on metamorphopsia in patients with branch retinal vein occlusion (BRVO), and to assess the relationship between metamorphopsia and inner retinal microstructure and other factors. Thirty-three treatment-naïve eyes of 33 patients with macular edema caused by BRVO with at least 12 months of follow-up were included. The degree of metamorphopsia was quantified using the M-CHARTS. Retinal microstructure was assessed with spectral-domain optical coherence tomography. Disorganization of the retinal inner layers (DRIL) at the first month after resolution of the macular edema (early DRIL) and at 12 months after treatment (after DRIL) was studied. Central retinal thickness (CRT), and status of the external limiting membrane as well as ellipsoid zone were also evaluated. IVR treatment significantly improved best-corrected visual acuity (BCVA) and CRT, but the mean metamorphopsia score did not improve even after 12 months. Post-treatment metamorphopsia scores showed a significant correlation with pre-treatment metamorphopsia scores (P < 0.005), the extent of early DRIL (P < 0.05) and after DRIL (P < 0.05), and the number of injections (P < 0.05). Multivariate analysis revealed that the post-treatment mean metamorphopsia score was significantly correlated with the pre-treatment mean metamorphopsia score (P < 0.05). IVR treatment significantly improved BCVA and CRT, but not metamorphopsia. Post-treatment metamorphopsia scores were significantly associated with pre-treatment metamorphopsia scores, the extent of DRIL, and the number of injections. Prognostic factor of metamorphopsia was the degree of pre-treatment metamorphopsia.

Purpose: To test the safety and preliminary efficacy of rapid, nonpharmacologic anesthesia via cooling for intravitreal injections., Design: Single-center, randomized phase 1 dose-ranging safety study (ClinicalTrials.gov identifier, NCT02872012)., Participants: Adults 18 years of age or older with a diagnosis of exudative macular degeneration or diabetic macular edema requiring bilateral anti-vascular endothelial growth factor therapy were included., Methods: A handheld device was developed to provide anesthesia via cooling to a focal area on the surface of the eye before intravitreal treatment (IVT). In 22 patients undergoing bilateral IVT, 1 eye was randomized to receive standard of care (SOC) lidocaine-based anesthesia and the other eye received cooling-anesthesia at 1 of 5 different temperatures and cooling times. Subjective pain was assessed via the visual analog scale (VAS; range, 1-10) at 2 time points: (1) immediately after IVT and (2) 4 hours after IVT. Treated eyes were assessed for ocular safety 24 hours after IVT., Main Outcome Measures: We determined the occurrence of adverse events in eyes treated with cooling anesthesia. Mean VAS pain scores immediately after IVT and 4 hours after IVT in eyes receiving cooling anesthesia were compared with eyes receiving SOC., Results: A total of 44 eyes were treated, 22 with cooling anesthesia and 22 with SOC. No dose-related toxicity was found with cooling anesthesia. Mild, transient adverse events were recorded in 32% of patients treated with cooling anesthesia versus 44% of patients receiving SOC. The mean±standard error of the mean (SEM) VAS pain scores immediately after intravitreal injection were 2.3 ± 0.4 for patients receiving SOC and 2.2 ± 0.6 in patients receiving -10° C cooling anesthesia (P = 0.8). Mean±SEM pain scores 4 hours after injection were 1.6 ± 0.4 for SOC and 1.2 ± 0.5 in the combined -10° C arms (P = 0.56). Total mean±SEM procedure time was 124 ± 5 seconds for patients treated with cooling anesthesia versus 395 ± 40 seconds for SOC (P < 0.0001)., Conclusions: Ultra-rapid cooling of the eye for anesthesia was well tolerated, with -10° C treatment resulting in comparable levels of anesthesia to SOC with a reduction in procedure time., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Opticin is an endogenous vitreous glycoprotein that may have therapeutic potential as it has been shown that supranormal concentrations suppress preretinal neovascularization. Herein we investigated the pharmacokinetics of opticin following intravitreal injection in rabbits. To measure simultaneously concentrations of human and rabbit opticin, a selected reaction monitoring mass spectrometry assay was developed. The mean concentration of endogenous rabbit opticin in 7 uninjected eyes was measured and found to be 19.2 nM or 0.62 μg/mL. When the vitreous was separated by centrifugation into a supernatant and collagen-containing pellet, 94% of the rabbit opticin was in the supernatant. Intravitreal injection of human opticin (40 μg) into both eyes of rabbits was followed by enucleation at 5, 24, and 72 h and 7, 14, and 28 days postinjection ( n = 6 at each time point) and measurement of vitreous human and rabbit opticin concentrations in the supernatant and collagen-containing pellet following centrifugation. The volume of distribution of human opticin was calculated to be 3.31 mL, and the vitreous half-life was 4.2 days. Assuming that rabbit and human opticin are cleared from rabbit vitreous at the same rate, opticin is secreted into the vitreous at a rate of 0.14 μg/day. We conclude that intravitreally injected opticin has a vitreous half-life that is similar to currently available antiangiogenic therapeutics. While opticin was first identified bound to vitreous collagen fibrils, here we demonstrate that >90% of endogenous opticin is not bound to collagen. Endogenous opticin is secreted by the nonpigmented ciliary epithelium into the rabbit vitreous at a remarkably high rate, and the turnover in vitreous is approximately 15% per day.

Objective: This study was conducted to evaluate the effects of anti-vascular endothelial growth factor (VEGF) antibody (bevacizumab) on vascular leakage and fibrosis in a monkey choroidal neovascularization (CNV) model. The relationship between fibrotic tissue and subretinal hyper-reflective material (SHRM), in optical coherence tomography (OCT) images, was also investigated., Methods: Experimental CNV was induced in male cynomolgus monkeys by laser photocoagulation. Intravitreal injection of bevacizumab at 0.5 mg/eye/dosing was initiated 2 weeks before or after laser irradiation and thereafter, conducted intermittently at 2- or 3-week intervals. Fluorescein fundus angiography (FA) and OCT imaging were conducted weekly from 2 to 7 weeks after laser irradiation. CNV leakage was evaluated by an established grading method using FA images. To assess the fibrosis and scarring, Masson's trichrome specimens of each CNV lesion were prepared, and morphometric analysis was conducted using an image analysis software., Results: The effects of bevacizumab on vascular leakage were shown using an established evaluation method. Morphometric analysis of Masson's trichrome-stained (MT) specimens revealed that collagen fiber synthesis was suppressed by bevacizumab pre-treatment (-29.2%) or post-treatment (-19.2%). SHRM was detected in OCT images in a monkey CNV model, and a significant correlation between the SHRM area in the OCT images and the collagen fiber area in the MT specimens was noted., Conclusion: In the established cynomolgus monkey CNV model, bevacizumab prevented blood leakage but could not completely suppress fibrosis. SHRM in the OCT images reflected retinal fibrous tissue in a laser-induced CNV monkey model. This model might be useful for elucidating the pathology and development therapy for neovascularization or fibrosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: To analyze contrast sensitivity of intravitreal bevacizumab injections with optimizing glycemic control versus optimizing glycemic control (in combination with sham injections) in eyes with Diabetic Macular Edema (DME)., Design: Prospective, interventional, masked, randomized controlled trial., Methods: Forty-one eyes of 34 patients with type 2 diabetes mellitus and DME with glycated hemoglobin (HbA1c) < 11% received either intravitreal bevacizumab injection (Group 1) or sham injection (Group 2) at 0 and 6 weeks along with optimizing glycemic control. Mean change in best-corrected visual acuity (BCVA), contrast sensitivity (CS), optical coherence tomography (OCT)-measured by central macular thickness (CMT) were compared and correlated at baseline, 2, 6 and 12 weeks., Results: The study showed a mean CS improved in group 1 from 1.14 ± 0.36 logCS to 1.32 ± 0.24 logCS and also in group 2 from 1.11 ± 0.29 logCS to 1.18 ± 0.29 logCS at 12 weeks (P = 0.12). CS and CMT promptly decreased in group 1 compared to group 2 at 2 weeks (ΔCS = 0.15 ± 0.25 vs. 0.03 ± 0.15 logCS; P = 0.04; ΔCMT = 116 ± 115 vs. 17 ± 71 μm; P = 0.01). There was a mean reduction of approximately 0.5% in HbA1c levels in both groups at 12 weeks (P = 0.002)., Conclusion: The use of bevacizumab in combination with optimizing glycemic control results in earlier improvement of contrast sensitivity in type 2 diabetes patients with DME. However, the optimizing glycemic control itself has shown also to be effective at 12 weeks. ClinicalTrials.gov Identifier: NCT02308644., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This retrospective study was to compare the efficacy of intravitreal injection of ranibizumab and aflibercept for patients with pachychoroid neovasculopathy. 54 eyes were initially treated with 3 monthly loading injections of ranibizumab or aflibercept. Treatment switching from ranibizumab to aflibercept, and aflibercept to photodynamic therapy was done at 3 months in case of incomplete fluid absorption. At 3 months, the rate of complete fluid absorption was significantly higher in the aflibercept-treated group than in the ranibizumab-treated group (82.6% vs 51.6%, p = 0.018). The mean reduction of subfoveal choroidal thickness was significantly greater in the aflibercept group than in the ranibizumab group (-35 µm vs -9 µm, p = 0.013). There was no significant difference between the two groups in terms of visual improvement or decrease in central macular thickness. Complete fluid absorption was achieved after switching from ranibizumab to aflibercept in 13 of 15 eyes (86.7%). Adjunctive photodynamic therapy was required in 6 eyes. In conclusion, treatment mainly with anti-vascular endothelial growth factor effectively improved visual acuity within 12 months (from 20/56 to 20/44 at 3 months and to 20/36 at 12 months). Aflibercept was superior to ranibizumab in achieving dry macula and reducing choroidal thickness at 3 months.

Purpose: To describe a technique for extemporaneously drawing up bevacizumab for intravitreal injection (IVT) and report the rate of post-injection endophthtalmitis., Patients and Methods: Retrospective monocentric analysis (January 2010-December 2014) of all IVT of bevacizumab drawn up with the following technique: in the operating room (class ISO 7) through a mini-spike with an integrated bacteria retentive air filter. The surgeon was wearing sterile gloves and a mask. The assisting nurse wore a mask. The bevacizumab vial was discarded at the end of each session., Results: Six thousand two hundred and thirty-six bevacizumab injections were performed. One case of endophthalmitis was noted (0.016%). During the same period, 4 cases of endophthalmitis were found after IVT of other drugs (4/32,992; 0.012%. P=0.8)., Conclusion: Intravitreal injection of bevacizumab after extemporaneous withdrawal through a mini-spike filter is a simple and safe technique. The risk of postoperative endophthalmitis is very low. This simple technique facilitates access to compounded bevacizumab., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The advantage of intravitreal injections is an immediate and increased therapeutic effect in the intended retinal tissue. The accuracy, precision and reproducibility of the delivered volume depend on the size of the syringe and the physician's manual experience. The eyelids and eyelashes are usually disinfected using a povidone-iodine solution (10%); a sterile speculum is placed and drops of povidone-iodine (5%) are applied. The use of adequate anesthetic topical lidocaine 2% is required. The injection site should be located 3.5-4 mm posterior to the limbus. The angle of the incision through the sclera may be directed in an oblique fashion of 30°. The diameter of the needle should be smaller than 25 G, and the injected volume should be limited to 0.15 ml without a routine paracentesis. The incidence of lens injury is 0.006% (2/32,318) and 0.013% (5/35,942) for rhegmatogenous retinal detachments. The rate of suspected endophthalmitis is 0.018% after bevacizumab and 0.027% after ranibizumab injections. Sterile inflammations have been observed after Avastin injections. The concentrations of vascular endothelial growth factor inhibitors decline in a monoexponential fashion. The half-life of unbound bevacizumab is 9.82 days and that of ranibizumab 7.19 days., (© 2016 S. Karger AG, Basel.)

Purpose: To evaluate 2-year outcomes following intravitreal bevacizumab (IVB) as monotherapy for aggressive posterior retinopathy of prematurity (APROP)., Methods: Medical records of 40 infants were retrospectively reviewed. Group I included infants who had received IVB injections for APROP. Group II included infants who underwent laser treatment for APROP. Anatomic and refractive outcomes and the presence of anisometropia and strabismus were assessed at follow-up examinations., Results: Group I included 48 eyes of 25 infants (11 males) with a mean gestational age (GA) of 26.40 ± 1.82 weeks and a mean birth weight (BW) of 901.40 ± 304.60 g. Group II included 30 eyes of 15 infants (6 males) with a mean GA of 27.30 ± 1.82 weeks and a mean BW of 941.00 ± 282.48 g. GA, BW, and gender distributions were similar between groups (P=0.187, P=0.685, and P=1.000, respectively). Refractive errors were significantly less myopic in group I (0.42 ± 3.42 D) than in group II (-6.66 ± 4.96 D) at 2 years (P=0.001). Significantly higher rates of anisometropia and strabismus were observed in group II than in group I (P=0.009 and P=0.036, respectively)., Conclusions: The study demonstrated that IVB monotherapy can be useful in the treatment of APROP. The decreased incidence of early unfavorable refractive and functional outcomes in the IVB group compared with the laser group showed a potential benefit for patients treated with IVB, and this needs to be better evaluated in future prospective studies.

Purpose: To report the anatomical and visual results in patients diagnosed as having retinal pigment epithelium (RPE) tears after receiving ranibizumab injections., Methods: Eyes diagnosed as having RPE tears with a minimum 6-month follow-up were retrospectively evaluated. Each eye was treated with at least three doses of ranibizumab at monthly intervals. Best-corrected visual acuity (BCVA), anterior segment findings, intraocular pressure, and fundus examination results were evaluated during control visits. Color fundus photography, fundus fluorescein angiographies, fundus autofluorescence, and spectral domain optical coherence tomography (SD-OCT) images were obtained. The height of pigment epithelial detachment (PED) was measured by SD-OCT., Results: Twelve eyes with RPE tears were studied. Nine eyes (75%) developed RPE tears during ranibizumab injections for choroidal neovascularization (eight eyes with vascularized PED and one eye with choroidal osteoma), and tears occurred in three eyes before any injections. The median number of ranibizumab injections after diagnosis of RPE tears was 3 (min 2, max 5). In the most recent follow-up visit, there was no statistically significant correlation between the grade of RPE and logMAR of BCVA (p>0.05, r=0.112). Eight of twelve eyes had PED, and seven of these had irregular PED contours before injection therapy. The mean PED height was 447 ± 122 µm., Conclusions: In this series, RPE tears developed mostly after intravitreal anti-VEGF injections for vascularized PED. Increased vertical height and irregular contours of the PEDs can be risk factors for the formation of RPE tears. The continuation of anti-VEGF therapy after tear formation is beneficial for vision improvement in eyes with RPE tears.

A 33-year-old man presented with vision loss in his right eye due to rhegmatogenous retinal detachment, for which he underwent pars plana vitrectomy with silicone oil injection. Three months later, the patient presented with sudden vision loss. On examination, his visual acuity was 20/200 with presence of subretinal haemorrhage with attached retina and silicone oil in situ. Fluorescein angiography confirmed the diagnosis of choroidal neovascularisation (CNV). The patient underwent intravitreal ranibizumab injection (0.5 mg per 0.05 mL). He subsequently underwent oil removal along with intravitreal bevacizumab injection (1.25 mg per 0.05 mL). The CNV completely regressed. At 7 years follow-up, the patient's best corrected visual acuity was 20/50 with attached retina and macular scar due to regressed CNV. His other eye was within normal limits throughout the follow-up period. This unique case demonstrates the successful outcome of intravitreal ranibizumab injection in a silicone oil-filled eye with myopic CNV., (2015 BMJ Publishing Group Ltd.)

Purpose: The perfect intravitreal injection delivers an exact amount of medication with the least risk to vision and the eye. We examined 2 different methods of intravitreal injection to determine if an angled transscleral entry for intravitreal injection results in less egress of intravitreal contents, including medication., Methods: In a crossover controlled trial at an outpatient clinical facility within a major ophthalmology referral center, we treated 10 patients. The surgical technique involved injecting 0.05 mL of bevacizumab injected in one eye by both an orthogonal (straight in) and oblique (angled) technique. The intraocular pressure (IOP) was measured immediately before and after each monthly injection., Results: Orthogonal injections raised the IOP significantly less (mean 24.6 mm Hg or 126%) than oblique injections (29.6 mm Hg or 152%) (p = 0.045). There were no reported differences in injection-related pain or adverse effects between the techniques., Conclusions: Oblique or angled injections caused a larger IOP rise than straight or orthogonal injections. This finding suggests that oblique injections are self-sealing, deliver a higher dose of medication, or prevent vitreous reflux as well as close a potential portal of entry for pathogens.

Purpose: To describe the management of a patient with neovascular age-related macular degeneration and an implantable miniature telescope., Methods: Clinical case report., Results: The patient developed recurrent choroidal neovascularization after telescope implantation and was successfully managed with a series of anti-vascular endothelial growth factor injections and serial ocular coherence tomography through the telescope., Conclusion: Intravitreal injections can be safely performed in an eye with a telescope using standard ocular coherence tomography imaging and taking into consideration the unique geometric dimensions of the telescope.

Background and Objective: To determine whether patients prefer topical anesthesia or subconjunctival anesthesia for intravitreal injection., Patients and Methods: Consecutive patients receiving bilateral simultaneous injections of anti-vascular endothelial growth factor agents were asked to participate in this within-patient, prospective, single-blinded, randomized, factorial study. Fifty-seven patients completed the study. Both eyes were treated with topical anesthesia. One eye was also injected with subconjunctival lidocaine. Anesthesia for the next treatment visit was based on patient preference at the conclusion of the study visit and at a 4-hour and 24-hour follow-up telephone call. Patients were allowed to change their anesthesia preference during the next three visits. The final endpoint for the study was anesthesia preference for ongoing intravitreal injections., Results: Fifty patients (88%) preferred subconjunctival anesthesia and seven patients (12%) preferred topical anesthesia for ongoing treatments. (P = .0003) CONCLUSION: Given the choice, most patients prefer subconjunctival anesthesia to topical anesthesia for intravitreal injections., (Copyright 2014, SLACK Incorporated.)

Diabetic retinopathy is the leading cause of visual impairment and preventable blindness, and represents a significant socioeconomic cost for health care systems worldwide. Therefore, new approaches beyond current standards of diabetes care are needed. Based on the crucial pathogenic role of vascular endothelial growth factor (VEGF) in the development of diabetic macular edema (DME), intravitreal anti-VEGF agents have emerged as new treatments. To provide an understanding of the rationale for use and clinical efficacy of anti-VEGF treatment, we examine this topic in a two-part Bench to Clinic narrative. In the Bench narrative, we provide an overview of the role of VEGF in the pathogenesis of diabetic retinopathy, the molecular characteristics of anti-VEGF agents currently used, and future perspectives and challenges in this area. In the Clinic narrative that follows our contribution, Cheung et al. provide an overview of the current evidence from clinical trials on anti-VEGF therapy for diabetic retinopathy.

Terminology of persistent diabetic macular edema has been initially reserved to cases unresponsive to conventional laser photocoagulation according to ETDRS criteria. While knowledge about pathophysiology of macular edema evolved and new drugs became available, the terminology of persistent diabetic macular edema expanded to include resistance to most current therapies. The purpose of this paper is to review medical and surgical options in the treatment of such difficult cases according to literature data and personal experience.

Purpose: To describe an alternative technique for avoiding contact with the lids and eyelashes without the use of a metal lid speculum along with the results in clinical practice., Methods: Retrospective review of the medical records of all patients undergoing intravitreal injections of bevacizumab and ranibizumab with lid retraction achieved by bimanual assisted eyelid retraction between November 2010 and December 2011., Results: A total of 10,164 consecutive intravitreal injections were performed, of which 3,834 were bevacizumab and 6,330 were ranibizumab. In this cohort of patients, 3 suspected cases of endophthalmitis developed (2 culture-negative), corresponding to a rate of 0.03%., Conclusion: The technique of bimanual assisted eyelid retraction for intravitreal injection has a low rate of infection similar to the reported rates using a metal lid speculum.

Intravitreal injection is a common procedure performed by ophthalmologists. It is a quick and targeted treatment for a number of ophthalmic conditions. Despite this, the potential to cause serious complications and patient discomfort cannot be ignored. This article presents the level of evidence in the scientific literature supporting common practices such as location of the procedure, anaesthetic choice, sterile procedure techniques, comparison of some common pharmaceutical agents and the use of antibiotics., (© 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To asses the anatomical and functional results after intravitreal bevacizumab administration in choroidal neovascularization secondary to pathologic myopia; To asses the safety and results stability;, Methods: Prospective, interventional case study of 18 eyes with choroidal neovascularization secondary to pathologic myopia treated with 1.25 mg. intravitreal bevacizumab (AVASTIN). Intravitreal injection was repeated, if needed, at 4-6 weeks until leakage stopped. In all cases fluorescein angiograms and Spectral 3D OCTs were performed. Visual acuity was measured with ETDRS optotype. Cases were followed-up at least 6 months. Statistical analysis was performed using ANOVA and Wilcoxon tests., Results: Mean age of patients in the study was 43.86%--6.32 years (ranging 24-62 years). The mean number of intravitreal injections was 2.62%--0.53 (ranging between 1 - 4 injections). Mean visual acuity improved in all cases. An increase of more than 15 letters was noted in 44.44.% of the cases. OCT confirmed a reduced depth of lesion and also a reduced lesion volume after treatment. No major local or systemic side-effects were noted. At 6 months follow-up the choroidal neovascularization reappeared in 5 cases (27.77%) requiring additional treatment., Conclusions: These results confirm the efficacy and safety of intravitreal bevacizumab in controlling the choroidal neovascularization secondary to pathologic myopia. More than 40% of the cases regained at least 3 lines in ETDRS chart but a recurrence was noted in 27.77% of the cases at 6 months.

Purpose: Malignant hypertensive retinopathy is a rare, but serious, complication of uncontrolled systemic hypertension for which no treatment has been established yet. We report 2 patients with malignant hypertensive retinopathy who recovered promptly following intravitreal bevacizumab injection., Methods: Intravitreal bevacizumab (1.25 mg/0.05 mL) was injected in 4 eyes of 2 patients having malignant hypertensive retinopathy with optic disc edema, macular edema, and retinal exudates. A complete ophthalmic examination, including the best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography (OCT), and fluorescein angiography (FAG), was performed before and after the treatments., Results: Two eyes in 1 patient received two intravitreal injections of bevacizumab, whereas 2 eyes in the other patient received a single treatment. All 4 eyes had improvement of macular edema on OCT at 1 month and decreased fluorescein leakage on FAG 3 months after the treatment, which led to improvements in the BCVA in 3 eyes. In 1 eye with foveal atrophy, no change in the BCVA occurred despite the improved macular edema on OCT., Conclusions: The results suggest that intravitreal bevacizumab injections might be a useful adjunctive treatment of malignant hypertensive retinopathy in some selected cases. However, further studies are mandatory to determine the safety and the efficacy of such injections in this disease.

Case Report: We report 2 cases of pseudoxanthoma elasticum with angioid streaks and choroidal neovascularization (CNV) in both eyes. Intravitreal ranibizumab (Lucentis) was administered with successful results in both cases., Discussion: CNV has been reported to occur in 72% to 86% of patients with angioid streaks. Although uncommon, the impact of CNV is important because it tends to affect people of working age. Based on the effectiveness of ranibizumab in other secondary CNVs, we decided to use it in our patients, observing the functional and anatomical improvement., (Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.)

Purpose: To determine whether bevacizumab and ranibizumab remain confined within the vitreous cavity after intravitreal injection and to determine the pharmacokinetic properties of these agents within the vitreous cavity., Methods: Radiolabeling with I-124 was completed using a modified Iodogen method. After testing for radiochemical purity, three anesthetized Dutch-belted rabbits underwent intravitreal injection with I-124 bevacizumab, and three underwent it with I-124 ranibizumab. All rabbits were imaged with a Micro PET-CT scanner on days 0, 2, 5, 7, 14, 21, 28, and 35., Results: The intravitreally placed radiolabeled agents were found to be contained within the vitreous cavity for the duration of the study with no extravasation into the central nervous system or elsewhere. I-124 bevacizumab was detectable until day 28, whereas I-124 ranibizumab was detectable until day 21. The kinetic model appears to represent a two-compartment model, and the average retention times for bevacizumab and ranibizumab after correction for radioactive decay were found to be 4.2 days and 2.8 days, respectively., Conclusions: There was no significant escape of bevacizumab and ranibizumab from the vitreous cavity after intravitreal injection. After correction for radioactive decay, both agents remained detectable until 28 and 21 days, respectively, with retention properties that validated those methods reported in previous studies.

This article aims to provide an interpretation and perspective on current concepts and recent literature regarding the evidence for individualizing intravitreal therapy (IVT), particularly considering iatrogenic and patient factors in the management of neovascular age-related macular degeneration (AMD). As ocular parameters that govern IVT pharmacokinetics do vary between individuals with AMD, developing a personalized strategy could improve safety and efficacy. This has to be derived from clinical measurements and data from laboratory animals; however, it is recognized that the animal models used in the development of intraocular formulations differ in their vitreous geometry from humans. These factors may be of relevance to the design of ophthalmic formulations and optimizing treatment outcomes in AMD. Further studies are needed to drive improvements in clinical practice which are aimed at maximizing the efficacy profile in IVT for AMD by a more rigorous evaluation of patient and surgeon-related variables., (Copyright © 2010 Elsevier Ltd. All rights reserved.)