Efficacy of subthreshold micropulse laser photocoagulation therapy versus anti-vascular endothelial growth factor therapy for refractory macular edema secondary to non-ischemic branch retinal vein occlusion.

OBJECTIVE: To assess the efficacy of subthreshold micropulse laser photocoagulation (SMLP) therapy versus anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with refractory macular edema (ME) secondary to non-ischemic branch retinal vein occlusion (BRVO). METHODS: This single-center, prospective, nonrandomized, case-control trial involved patients with refractory ME that responded poorly to three or more initial anti-VEGF injections. The patients were examined and divided into two groups according to their chosen treatment: the intravitreal ranibizumab (IVR) group and the SMLP group. Both groups were followed up monthly for 12 months. Therapeutic efficacy and safety were assessed throughout the follow-up period. RESULTS: The IVR group comprised 49 eyes, and the SMLP group comprised 45 eyes. The improvements in the optical coherence tomography findings and visual acuity were comparable between the two groups at the final follow-up. The total number of injections was significantly lower in the SMLP than IVR group. No serious adverse events occurred during the study period. CONCLUSIONS: SMLP therapy is better for patients with central macular thickness (CMT) of ≤400 µm. For patients with CMT of >400 µm, we advise continuation of anti-VEGF agents to reduce ME followed by application of SMLP therapy when CMT has decreased to ≤400 µm.

Risk of Intraocular Pressure Increase With Intravitreal Injections of Vascular Endothelial Growth Factor Inhibitors: A Cohort Study.

PURPOSE: Intraocular pressure increase (IOPi) after intravitreal injections of vascular endothelial growth factor inhibitors (VEGFis) might be different among different VEGFis (bevacizumab, aflibercept, ranibizumab). The purpose of this study was to evaluate the risk of IOPi among new users of bevacizumab, ranibizumab, and aflibercept in nondiabetic patients in Tuscany, Italy. DESIGN: Retrospective cohort study. METHODS: Tuscan regional administrative database was used to identify subjects with a first VEGFi intravitreal injection between 2011 and 2020, followed to first incidence of IOPi. Diabetic subjects, those with pre-existing IOPi, or previous use of dexamethasone implants were excluded. Multivariable Cox regression analyses (intention-to-treat and as treated) were conducted to evaluate risk of IOPi among aflibercept, bevacizumab, and ranibizumab, adjusting for potential confounding variables. IOPi was defined as the first record of International Classification of Diseases, Ninth Revision (ICD-9-CM) code 365 or use of 2 glaucoma drugs dispensations within 180 days of each other. RESULTS: We identified 6585 new users of VEGFis: 1749 aflibercept, 1112 bevacizumab, and 3724 ranibizumab. Women made up 60% of the cohort, with a mean age of 73.6 years. In the intention-to-treat analysis, the adjusted hazard ratio (HR) for incident IOPi, compared with aflibercept, was higher for bevacizumab (HR = 2.20, 95% CI = 1.64-2.95) and ranibizumab users (HR = 1.88, 95% CI = 1.46-2.42), respectively. The HRs remained robust after exclusion of patients with proxy of retinal vascular occlusion. As treated analysis confirmed such results (bevacizumab: HR = 3.76, 95% CI = 2.30-6.17; ranibizumab: HR = 2.49, 95% CI = 1.62-3.82). CONCLUSIONS: This study found an increased risk of IOPi among nondiabetic patients with ranibizumab and bevacizumab compared with aflibercept. Future studies are needed to validate these findings.

Hydrogels in Ophthalmology: Novel Strategies for Overcoming Therapeutic Challenges.

The human eye's intricate anatomical and physiological design necessitates tailored approaches for managing ocular diseases. Recent advancements in ophthalmology underscore the potential of hydrogels as a versatile therapeutic tool, owing to their biocompatibility, adaptability, and customizability. This review offers an exploration of hydrogel applications in ophthalmology over the past five years. Emphasis is placed on their role in optimized drug delivery for the posterior segment and advancements in intraocular lens technology. Hydrogels demonstrate the capacity for targeted, controlled, and sustained drug release in the posterior segment of the eye, potentially minimizing invasive interventions and enhancing patient outcomes. Furthermore, in intraocular lens domains, hydrogels showcase potential in post-operative drug delivery, disease sensing, and improved biocompatibility. However, while their promise is immense, most hydrogel-based studies remain preclinical, necessitating rigorous clinical evaluations. Patient-specific factors, potential complications, and the current nascent stage of research should inform their clinical application. In essence, the incorporation of hydrogels into ocular therapeutics represents a seminal convergence of material science and medicine, heralding advancements in patient-centric care within ophthalmology.

Clinical and visual outcomes following endogenous endophthalmitis: 175 consecutive cases from a tertiary referral center in Taiwan.

BACKGROUND: To elucidate the linkage between organisms and visual outcome in cases of endogenous endophthalmitis. METHODS: Patients who presented with signs of endogenous endophthalmitis between January 2008 and December 2015 and underwent a vitreous tapping were enrolled. The patients' demographics and clinical findings were recorded. The outcomes include visual acuity and enucleation. RESULTS: A total of 175 consecutive patients with endogenous endophthalmitis were enrolled. Forty-four percent of the patients had a known distal focus of infection. The most common focus was liver abscess (24.6%), and the major intravitreal isolate was Klebsiella pneumoniae (34.4%). In this series, 51.4% of the intravitreal cultures were positive. The visual acuity of fungal ophthalmitis were better than in bacterial ophthalmitis. Multivariate logistic regression showed that Gram negative vitreous isolates, compared with the negative vitreous culture, were associated with higher risk of enucleation (Odds ratio [OR]: 10.424, 95% confidence interval [95% CI]: 3.019-35.995). The use of intravitreal antibiotics, compared non-users, was associated with a reduced risk of enucleation (OR:0.084, 95% CI: 0.026-0.268). Trans pars plana vitrectomy was not associated with risk of enucleation (OR: 0.307, 95% CI: 0.035-2.693). The post-treatment VA was positively correlated with the presenting VA (r = 0.718, p = 0.0001). CONCLUSION: Our study demonstrated that liver abscess is the most common source of endogenous endophthalmitis in Taiwan. The visual outcome is good when the presenting visual acuity is relatively well preserved and when the infecting organism is fungus. The use of intra-vitreal antibiotics reduces the risk of enucleation.

Use of an ultra-clean air flow for surgical field asepsis when performing intravitreous injections in an ambulatory surgical environment.

BACKGROUND: Intravitreal injection of medications is one of the most common procedures performed in ophthalmology. Intravitreal anti-VEGF agents are currently the chosen treatment for ocular fundus diseases, including age-related macular degeneration and diabetic retinopathy. As an invasive procedure it involves risks. The most serious complication from intravitreal injection of anti-VEGF agents is endophthalmitis (EO). Although rare, EO can result in devastating loss of vision. This article evaluates whether the use of an ultra-clean air flow (UA) can be another useful tool in the prevention of EOs. Accordingly, the maintenance of asepsis of the surgical field of intravitreal injections was verified with and without the use of UA. METHODS: The study was conducted in operating room of an ambulatory surgery center on four different surgical days when just intravitreal injections were scheduled. Two experiments using two Blood Agar and two Chocolate Agar plates (first 2 days; 4 plates by day) were carried out by positioning an UA directed to the surgical table and two other experiments (last 2 days; 4 plates per day) were carried out using similar plates without the use of the UA. All Blood Agar and four Chocolate Agar plates were positioned on the surgical table, close to the surgical filed. At the end of the day, after the conclusion of the intravitreous injections, the plates were sent for a biomolecular study that was carried out after 1 day of incubation at 37 °C. RESULTS: The sixteen plates, eight Blood Agar and eight Chocolate Agar, were analyzed qualitatively for the growth or not of microorganism's colonies and identification of their species. The biomolecular study demonstrated the growth of bacteria of the genus Micrococcus sp. with the use of the UA and without the the UA bacterias of the genera Bacillus sp, Staphylococcus haemolyticus, Staphylococcus aureus and Staphylococcus cohnii ssp urealyticus were found. CONCLUSION: The use of UA close to the operating table prevented the growth of pathogenic bacteria and should be considered as an alternative tool to avoid the contamination of materials and drugs used for intravitreal injections.

Intravitreous delivery of melatonin affects the retinal neuron survival and visual signal transmission: in vivo and ex vivo study.

Intravitreal delivery can maximize the intensity of therapeutic agents and extend their residence time within ocular tissue. Melatonin is a lipophilic molecule that crosses freely biological barriers and cell membranes. This study intends to investigate the effects of intravitreally delivered melatonin on mouse retina. The visual function of administered mice is assessed by electrophysiological and behavior examinations three weeks after intravitreal delivery. Moreover, multi-electrode array (MEA) was used to assess the electrical activities of retinal ganglion cells (RGCs). We found that intravitreal delivery of high dosage melatonin (400-500 µg/kg) destroyed the retinal architecture and impaired the visual function of mice. Conversely, the melatonin administration at low dose (100-300 µg/kg) did not have any significant effects on the photoreceptor survival or visual function. As shown in the MEA recording, the photoreceptors activity of the central region was more severely disturbed by the high dose melatonin. A pronounced augment of the spontaneous firing frequency was recorded in these mice received high dosage melatonin, indicating that intravitreal delivery of high dosage melatonin would affect the electrical activity of RGCs. Immunostaining assay showed that the vitality of cone photoreceptor was impaired by high dose melatonin. These findings suggest that intravitreal melatonin is not always beneficial for ocular tissues, especially when it is administered at high dosage. These data add new perspectives to current knowledge about melatonin delivery at the ocular level. Further therapeutic strategies should take into consideration of these risks that caused by delivery approach.

Expert opinion on the management and follow-up of uveitis patients during SARS-CoV-2 outbreak.

INTRODUCTION: Routine medical and ophthalmic care is being drastically curtailed in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Uveitis patients require particular attention because of their theoretical risk of viral infection, in the context of therapeutic immunosuppression. AREAS COVERED: This collaborative work proposes practical management and follow-up criteria for uveitis patients in the context of the ongoing SARS-CoV-2 pandemic. EXPERT OPINION: Management should proceed as usual when access to health care possible in patients who do not belong to a group at high risk of severe SARS-CoV-2 infection, and in uncontrolled uveitis cases. In case of reduced access to eye clinics or high risk of SARS-CoV-2 infection, patients' management should be stratified based on their clinical presentation. In non-severe uveitis cases, the use of systemic steroids should be avoided, and local steroids preferred whenever possible. In uncontrolled situations where there is real risk of permanent visual loss, high-dose intravenous steroids and/or systemic immunosuppressants and/or biotherapies can be administered depending on the severity of eye disease. Immunosuppressive therapy should not be withheld, unless the patient develops SARS-CoV2 infection.

Ghost cell glaucoma after intravitreous injection of ranibizumab in proliferative diabetic retinopathy.

BACKGROUND: The development of ghost cell glaucoma in patients with proliferative diabetic retinopathy (PDR) after intravitreous injection (IV) was rare. Here we reported a series of patients with PDR who received Intravitreous Ranibizumab (IVR) and developed ghost cell glaucoma and analyzed the potential factors that might be related to the development of ghost cell glaucoma. METHODS: Retrospective case series study. The medical records of 71 consecutive eyes of 68 PDR patients who received vitrectomy after IVR from January 2015 to January 2017 were reviewed. The development of ghost cell glaucoma after IVR was recorded. Characteristics of enrolled patients were retrieved from their medical charts. Factors associated with ghost cell glaucoma were compared between eyes with the development of ghost cell glaucoma and eyes without the development of ghost cell glaucoma. Variables were further enrolled in a binary backward stepwise logistic regression model, and the model that had the lowest AIC was chosen. RESULTS: There were 8 out of 71 eyes of the PDR patients developed ghost cell glaucoma after they received IVR. The interval between detection of elevation of intraocular pressure (IOP) and IV ranged from 0 to 2 days. Among them, after IVR, there were two eyes had IOP greater than 30 mmHg within 30 min, four eyes showed normal IOP at 30 min, and then developed ghost cell glaucoma within 1 day, two eyes developed ghost cell glaucoma between 24 and 48 h. The mean IOP was 46.5 ± 8.0 mmHg. All patients gained normal IOP after vitrectomy without medicine for lowering IOP. The presence of ghost cell glaucoma was associated with tractional retinal detachment (RR = 4.60 [2.02 ~ 8.48], p = 0.004) and fibrovascular membrane involving disk (RR = -3.57 [- 7.59 ~ - 0.92], p = 0.03) (AIC = 39.23, AUC = 0.88) in a logistic regression model. CONCLUSION: Attention to postoperative IOP should be paid to patients with PDR undergoing vitrectomy who receive a preoperative IV of anti-VEGF agents. PDR patients with tractional retinal detachment or fibrovasucular membrane involving optic disc are more likely to develop ghost cell glaucoma after IV.

Prefilled syringes for intravitreal drug delivery.

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) medications play an increasingly critical role in numerous retinal vascular diseases. Initially, anti-VEGF medications came in vials that had to be drawn up by the physician into a syringe for administration. In 2018, the US Food and Drug Administration (US FDA) approved the ranibizumab 0.3 mg prefilled syringe (PFS), and in October 2016, the US FDA approved the ranibizumab 0.5 mg PFS. This article discusses the advantages of the PFS, including reduced injection time, possible reduced risk of endophthalmitis, reduction in intraocular air bubbles and silicone oil droplets, and improved precision in the volume and dose of intravitreal ranibizumab administered, along with possible disadvantages. Implications of the innovation of the PFS on intravitreal injection technique and clinical practice pattern are discussed and reviewed.

Complications of Intravitreous Injections in Patients with Diabetes.

Intravitreous injections are presently the second most frequently performed ophthalmic procedure and the most common vitreoretinal procedure. In diabetic patients, intravitreous injections are frequently performed for the treatment of center-involved diabetic macular edema, proliferative diabetic retinopathy, or other co-existing retinal vascular disease. Diabetic patients may be at higher risk of adverse events compared to non-diabetic individuals, given frequent systemic comorbidities, such as cardiovascular and renal disease and increased susceptibility to infection. This review highlights the potential complications and safety considerations in intravitreous injections in patients with diabetes.

Embryonic Intravitreous Injection in Mouse.

Axons of retinal ganglion cells (RGCs) relay visual information from the retina to lateral geniculate nucleus (LGN) and superior colliculus (SC), which are two major image-forming visual nuclei. Wiring of these retinal projections completes before vision begins. However, there are few studies on retinal axons at embryonic stage due to technical difficulty. We developed a method of embryonic intravitreous injection of dyes in mice to visualize retinal projections to LGN and SC. This study opens up the possibility of understanding early visual circuit wiring in mice embryos.

Effects of intravitreous sodium hydrosulfide on intraocular pressure and retinopathy in ocular hypertensive rats.

We investigated the possible neuroprotectant and intraocular pressure (IOP) lowering effects of intravitreous injection of sodium hydrosulfide (NaSH) in a rodent model of experimental glaucoma. Glaucoma currently is treated by controlling IOP using medications and/or surgery. These methods are not entirely adequate for all patients. We divided 24 rats into three groups. For the control group, the right eye was treated with intravitreous saline. For the glaucoma group, ocular hypertension was induced by photocoagulating three episcleral veins and the limbal plexus of the right eye using an argon laser, then saline was injected into the vitreous of these eyes during the third week. For the NaSH group, rats were treated with intravenous NaSH 3 weeks after photocoagulation. IOP was measured each week during the 6 week experimental period. Coagulating the episcleral veins rapidly increased the IOP of rat eyes. Intravitreous injection of NaSH significantly reduced IOP. Intravitreous NaSH prevented degeneration of the retina and decreased the number of apoptotic cells. Intravitreous NaSH appeared to reduce IOP and to prevent IOP induced retinopathy in rats.

Effects of retrobulbar or intravitreal injection of triamcinolone acetonide combined with laser photocoagulation for diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the clinical efficacy of retrobulbar or intravitreal injection of triamcinolone acetonide combined with 532nm laser photocoagulation in the treatment of diabetic macular edema(DME). <p>METHODS: Sixty-two eyes in 40 DME patients were divided into two groups(Group A and Group B)randomly. Thirty-one eyes in Group A were treated with retrobulbar injection of triamcinolone acetonide(RBTA)and 31 eyes in Group B were treated with intravitreous injection of triamcinolone acetonide(IVTA). Eyes with limited macular edema were treated by local direct retinal laser, those with diffuse and cystic macular edema were treated by grid retinal laser using Vitra 532nm fundus lasers at 1mo after injection. Visual acuity, intraocular pressure, fundus, macular edema and complications were recorded after 1wk, 1, 3 and 6mo in the follow-up study. <p>RESULTS: The mean best corrected visual acuity was improved and macular edema subsided after treatment in the two groups in the follow-up study at 1wk, 1, 3 and 6mo(<i>P</i><0.05), while there had no significant difference between groups(<i>P</i>>0.05). In Group A, significant efficiency rate was 39%(12/31), total effective rate was 90%(28/31). In Group B, significant efficiency rate was 39%(12/31), total effective rate was 94%(29/31). The follow-up study showed no retinal detachment, endophthalmitis, intraocular hemorrhage and other complications. <p>CONCLUSION: Triamcinolone acetonide injection combined with laser photocoagulation is an effective method for treatment of DME with significant effect, less adverse reactions, patient's vision improved effectively and macular edema reduced. No significant difference was noted in the treatment of DME between RBTA and IVTA.

Effect of scleral buckling with intravitreous gas injection for rhegmatogenous retinal detachment and influence on serum amino acids and VEGF / 国际眼科杂志(Guoji Yanke Zazhi)

· AIM:To study the clinical curative effect of scleral buckling (SB) combined with intravitreous gas injection in the treatment of rhegmatogenous retinal detachment (RRD) and the influence on serum levels of amino acids and vascular endothelial growth factor (VEGF).· METHODS:The clinical data of 150 RRD patients (150 eyes) in our hospital were retrospectively analyzed.And 81 patients (81 eyes) treated with scleral buckling alone were included into the non-gas injection group while 69 patients (69 eyes) treated with scleral buckling combined with intravitreous gas injection were included in the gas injection group.The surgical effect,serum levels of amino acids and VEGF before and after surgery were compared between the two groups.· RESULTS:There was no significant difference in retinal reattachment rate between the two groups at different time points after surgery (P＞ 0.05).The intraocular pressure of gas injection group at 3d after surgery was significantly higher than that of non-gas injection group (P＜ 0.05) but there was no significant difference in intraocular pressure between the two groups at 5d after surgery (P＞ 0.05).The uncorrected visual acuity of operative eye of the two groups was improved significantly after surgery (P＜ 0.05).Serum levels of histidine,glutamic acid,phenylalanine and VEGF levels in the two groups significantly decreased at 5d after surgery (P＜0.05),without significant difference between the two groups (P＞0.05).There was no significant difference in serum levels of arginine,leucine,isoleucine and glycine before and after treatment (P＞ 0.05).The total score of visual function related quality of life and scores of different dimensions significantly increased at 1mo after surgery (P＜0.05),without significant differences between the two groups (P＞ 0.05).There was no significant difference in the total incidence of postoperative complications between the gas injection group (7.2％,5/69) and the non-gas injection group (9.9％,8/81;P＞0.05).· CONCLUSION:Scleral buckling combined with intravitreous gas injection can help the early recovery of visual function and intraocular pressure in RRD patients,and reduce the levels of histidine,glutamic acid,phenylalanine and VEGF,and it has high safety.

Cambio de grosor macular central con la administración de Bevacizumab Intravítreo / Change in Central Macular Thickness after Administration of Intravitreous Bevacizumab

Antecedentes: El bevacizumab pertenece a una familia de medicamentos que inhiben la acción de los factores endoteliales de crecimiento vascular (VEGF, por sus siglas en inglés) aprobado por la FDA para el tratamiento de varios tipos de cáncer. Es un anticuerpo monoclonal que se une a todas las isoformas del VEGF evitando que la molécula se una a su receptor y active sus vías efectoras, disminuyendo así la proliferación de nuevos vasos inestables que por medio de fugas y rupturas que causan la acumulación de líquido en el espacio subrretiniano. Se ha utilizado de manera off-label para el tratamiento de las patologías proliferativas de la retina o coroides, con resultados prometedores. Objetivo: Determinar el efecto de la administración de 3 dosis de bevacizumab intravítreo sobre el grosor macular central medido por tomografía de coherencia óptica (OCT) después de 1 mes. Establecer una base de datos de las características epidemiológicas de los pacientes ­ edad, género, indicación de tratamiento, historia de diabetes e historia familiar de ceguera ­ y la respuesta al tratamiento con bevacizumab intravítreo. Metodología: Es un estudio cuasi-experimental retrospectivo de antes y después de una intervención. Se revisaron 261 expedientes clínicos para obtener los datos generales del paciente así como la medida de grosor macular central antes y 1 mes después de la administración de bevacizumab intravítreo por cualquier indicación. Los resultados luego fueron comparados utilizando la prueba T de Student para la diferencia de dos medias. Resultados: Al analizar a toda la población del estudio, se obtuvo una reducción de grosor macular central antes y después de la administración de bevacizumab de 19% (p < 0.0001). Esta diferencia no se observó en todos los grupos de pacientes al compararlos según la indicación de tratamiento. Conclusión: Se pudo observar un cambio significativo en la reducción del grosor macular central tras la administración de 3 dosis de bevacizumab intravítreo. Palabras Clave: Retinopatía, bevacizumab, anti-VEGF, intravítreo.

Background: Bevacizumab belongs to a group of monoclonal antibodies that act by binding to all isoforms of vascular endothelial growth factors (VEGF) thus preventing the activation of effector pathways that lead to formation of new and unstable blood vessels in the retina. It has been used off-label for the treatment of proliferative pathologies of the retina, with promising results. Objective: To determine the effect of a 3 doses administration of intravitreous bevacizumab on central macular thickness measured by optical coherence tomography (OCT) 1 month after the last injection and also to establish a database of the epidemiologic characteristics of the patients and their response to treatment with intravitreous bevacizumab. Method: This is a quasi-experimental retrospective design of before and after an intervention. A population of 261 cases reviewed to obtain general data of each patient as well as the central macular thickness measured by OCT before and 1 month after treatment with intravitreous bevacizumab. Results were then compared using Student's T test for the difference of two means. Results: A reduction of 19% (p < 0.0001) in central macular thickness measured by OCT was observed in the overall population of the study. These results did not apply to all patients when classified by indication of treatment (base pathology). Conclusion: Results suggest that a 3 dose treatment of intravitreous bevacizumab is effective in the reduction of mean central macular thickness measured by OCT 1 month after intervention. Keywords: Retinopathy, bevacizumab, anti-VEGF, intravitreous

[Treatment of macular edema: Comparison of efficacy and tolerability of subconjunctival triamcinolone injections, sub-tenon's triamcinolone injections and intravitreal dexamethasone implant]. / Traitement des œdèmes maculaires : comparaison de l'efficacité et de la tolérance des injections sous-conjonctivales de triamcinolone, des injections sous-ténoniennes de triamcinolone et des injections intra-vitréennes de l'implant de dexaméthasone.

The area of uveitis is related to numerous pathological entities. One of the main causes of decreased visual acuity in these patients is macular edema. One aspect of the treatment includes cortosteroids used peri- and intra-ocularly. MATERIALS AND METHODS: The goal of our work was to estimate the criteria of efficacy (on improvement in visual acuity and macular edema, as well as time to recurrence) and safety (on intraocular pressure and cataract) of these various routes of administration of corticosteroid after a single injection. We compared patients treated with Ozurdex® versus subconjonctival triamcinolone versus sub-tenon's triamcinolone. This is a retrospective study conducted in 2 tertiary centers, the university medical center of Nantes and La Pitié-Salpêtrière hospital from November, 2011 to November, 2013. RESULTS: At presentation, 25 % of the patients displayed VA better than 5/10. During follow-up, this proportion increased to 45 % at M1, 50 % at M3, 49 % at M6 and 48 % at the end of follow-up. There was no significant difference between the groups with respect to VA gain. The reductions in mean CMT compared with D0 were all statistically significant (improvement of one line in log-OCT). We observed an improvement in macular thickness of 88 % at M1, 86 % at M3, 61 % at M6 and 60 % at the end of follow-up, significant at each time, with no significant difference between the three groups. A comparison of time to anatomic vs. functional recurrence was performed, showing no difference. The largest increase in IOP was observed at M1, statistically different from the other time points. DISCUSSION: Intra- and periocular injections should be considered as an adjuvant therapy, since the majority of the conditions in question require systemic treatment. They allow for increased intravitreal concentrations with fewer systemic effects. CONCLUSION: We demonstrated neither any true superiority of any of the 3 treatments nor any difference in tolerability between the 3 groups.

Improved Intravitreal AAV-Mediated Inner Retinal Gene Transduction after Surgical Internal Limiting Membrane Peeling in Cynomolgus Monkeys.

The retina is an ideal target for gene therapy because of its easy accessibility and limited immunological response. We previously reported that intravitreally injected adeno-associated virus (AAV) vector transduced the inner retina with high efficiency in a rodent model. In large animals, however, the efficiency of retinal transduction was low, because the vitreous and internal limiting membrane (ILM) acted as barriers to transduction. To overcome these barriers in cynomolgus monkeys, we performed vitrectomy (VIT) and ILM peeling before AAV vector injection. Following intravitreal injection of 50 µL triple-mutated self-complementary AAV serotype 2 vector encoding EGFP, transduction efficiency was analyzed. Little expression of GFP was detected in the control and VIT groups, but in the VIT+ILM group, strong GFP expression was detected within the peeled ILM area. To detect potential adverse effects, we monitored the retinas using color fundus photography, optical coherence tomography, and electroretinography. No serious side effects associated with the pretreatment were observed. These results indicate that surgical ILM peeling before AAV vector administration would be safe and useful for efficient transduction of the nonhuman primate retina and provide therapeutic benefits for the treatment of retinal diseases.

Effect of photodynamic therapy combined with intravitreal ranibizumab injection on circumscribed choroidal hemangioma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the effect of photodynamic therapy(PDT)combined with intravitreal injection of ranibizumab on circumscribed choroidal hemangioma(CCH). <p>METHODS:A retrospective study was performed for 6 eyes(6 cases)diagnosed as CCH. Before treatment, OCT examination showed macular cystoid edema and retinal neurepithelium layer detachment in all patients. All patients underwent photodynamic therapy, then intravitreal injection of ranibizumab 0.5mg(0.05mL)were administered at 48h after PDT. The best corrected visual acuity(BCVA), examination of the ocular fundus, fundus photography, fluorescence fundus angiography(FFA), indocyanine green angiography(ICGA), eye B ultrasonic and optical coherence tomography(OCT)were performed respectively at 1, 3 and 6mo after treatment. <p>RESULTS:The patients were followed up for 4 to 10mo, the final vision of follow-up increased than before, it was raised 7 lines. The images of ICGA revealed hypofluorescence or no leakage in focal area. Eye B ultrasonic showed that hemangioma shrunk or faded. The images of ICGA revealed macular region retinal reattached well and edema disappeared completely. Mean flow-up was 6mo postoperative. There had no evidence of recurrence. <p>CONCLUSION:For CCH patients, hemangioma got smaller obviously by PDT. Intravitreal ranibizumab injection promote effusion absorption under the retina. Combining use of the two therapies could improve visual acuity in a short-term.

Prevalence of outer retinal tubulation in eyes with choroidal neovascularization.

BACKGROUND: Outer retinal tubulations (ORTs) are branching tubular structures located in the outer nuclear layer of the retina. The goal of this study is to determine the prevalence of ORTs observed in eyes with choroidal neovascularization (CNV) undergoing treatment with anti-angiogenic intravitreous injection (IVI) with anti-VEGF (vascular endothelial growth factor) at the Ophthalmology Department of a tertiary hospital in São Paulo, Brazil. METHODS: This is a descriptive study based on medical charts and Spectral-domain Optical Coherence Tomography (Sd-OCT) scans of 142 patients (158 eyes) treated between 2012 and 2014 with IVI of anti-VEGF for CNV. The patients' data was analysed according to age, gender, pathology, presence of ORTs, and best corrected visual acuity (BCVA). Patients with and without ORTs were compared according to the last BCVA obtained using Chi square corrected by the Yates factor. RESULTS: ORTs were found in a total of 40 out of 158 eyes (25.31 %) with CNV; in 33 out of 119 eyes (27.7 %) with neovascular age-related macular disease (AMD); in 5 out of 8 eyes (62.5 %) with neovascular angioid streaks; and in 2 out of 12 eyes (16.67 %) with myopic neovascular membranes. Most patients with ORTs had BCVA worse than 20/200, significantly worse BCVA than patients without ORTs. CONCLUSIONS: Recent studies have considered that the presence of ORTs is indicative of a photoreceptor degeneration process and may represent a final stage of multiple retinal degenerative pathologies. The prevalence of ORTs in eyes with CNV has not been well described, especially when considering the Brazilian population treated in a public health care system. In our study, ORTs were observed in only three different pathologies: neovascular AMD, neovascular angioid streaks and myopic neovascular membranes. The correct recognition of ORTs is fundamental for its differentiation from intraretinal cysts, for the latter is related to the activity of neovascular diseases, and usually guides anti-angiogenic therapy. We conclude that ORTs have a high prevalence in the population studied, and their correct identification presents relevant therapeutic implications.