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Problem definition: Cataract surgery and intravitreal injections are common treatmentsat eye clinics and these procedures can be preceded by worry and anxiety in the patient.It is the ophthalmic nurse's responsibility to work for good nursing care and promotewell-being for all patients. Increased knowledge of the ophthalmic nurse's experience ofmeeting patients with anxiety during eye procedures would therefore be valuable inpromoting health and well-being. Purpose: To explore ophthalmic nurses’ experiencesof meeting patients with anxiety associated with planned invasive procedures in the eye.Method: A qualitative interview study with semi-structured questions and an inductiveapproach was performed. Ten ophthalmic nurses from five eye clinics in Central andSouth of Sweden participated in the study. Results: The analysis resulted into threecategories and eight subcategories. The three categories where Anxiety vary,Circumstances that can affect anxiety and Anxiety can lead to consequences.Conclusion: The ophthalmic nurses´ experiences were that all patients were anxiouspreoperatively. Individualized information and person-centered nursing care reducedpatients´ anxiety. The importance of the team and specific nursing actions such ashandhold were also of value. Future studies could be interviews with ophthalmic nurses’or patients with focus on nursing actions that can calm anxiety., Problemformulering: Kataraktkirurgi och intravitreala injektioner är vanliga ingrepppå ögonmottagningar och dessa ingrepp kan föregås av oro och ångest hos patienten. Iögonsjuksköterskans ansvar ligger det att arbeta för en god omvårdnad och främjavälbefinnande för alla patienter. Ökad kunskap om ögonsjuköterskans erfarenhet avmötet med patienter med oro vid ingrepp i ögat skulle därför vara av värde för attfrämja hälsa och välbefinnande. Syfte: Att undersöka ögonsjuksköterskorserfarenheter av att möta patienter med oro i samband med planerade ingrepp i ögat.Metod: En kvalitativ intervjustudie med semistrukturerade frågor och induktiv ansatsgenomfördes. Tio ögonsjuksköterskor från fem ögonmottagningar i mellersta ochsödra Sverige deltog. Resultat: Analysen resulterade i tre kategorier och åttasubkategorier. De tre kategorierna var; Oro varierar, Omständigheter som kanpåverka oro, Oro kan leda till konsekvenser. Konklusion: Ögonsjuksköterskornahade en erfarenhet av att alla patienter hade någon form av oro preoperativt.Individanpassad information och ett personcentrerat omvårdnadsarbete var ett stöd föratt lindra oro hos patienterna. Teamets betydelse och specifika omvårdnadsåtgärdersom till exempel en hand att hålla var också av värde. Framtida studier kan varaintervjuer med ögonsjuksköterskor eller patienter med fokus på omvårdnadsåtgärdersom kan stilla oro.

Problem definition: Cataract surgery and intravitreal injections are common treatmentsat eye clinics and these procedures can be preceded by worry and anxiety in the patient.It is the ophthalmic nurse's responsibility to work for good nursing care and promotewell-being for all patients. Increased knowledge of the ophthalmic nurse's experience ofmeeting patients with anxiety during eye procedures would therefore be valuable inpromoting health and well-being. Purpose: To explore ophthalmic nurses’ experiencesof meeting patients with anxiety associated with planned invasive procedures in the eye.Method: A qualitative interview study with semi-structured questions and an inductiveapproach was performed. Ten ophthalmic nurses from five eye clinics in Central andSouth of Sweden participated in the study. Results: The analysis resulted into threecategories and eight subcategories. The three categories where Anxiety vary,Circumstances that can affect anxiety and Anxiety can lead to consequences.Conclusion: The ophthalmic nurses´ experiences were that all patients were anxiouspreoperatively. Individualized information and person-centered nursing care reducedpatients´ anxiety. The importance of the team and specific nursing actions such ashandhold were also of value. Future studies could be interviews with ophthalmic nurses’or patients with focus on nursing actions that can calm anxiety., Problemformulering: Kataraktkirurgi och intravitreala injektioner är vanliga ingrepppå ögonmottagningar och dessa ingrepp kan föregås av oro och ångest hos patienten. Iögonsjuksköterskans ansvar ligger det att arbeta för en god omvårdnad och främjavälbefinnande för alla patienter. Ökad kunskap om ögonsjuköterskans erfarenhet avmötet med patienter med oro vid ingrepp i ögat skulle därför vara av värde för attfrämja hälsa och välbefinnande. Syfte: Att undersöka ögonsjuksköterskorserfarenheter av att möta patienter med oro i samband med planerade ingrepp i ögat.Metod: En kvalitativ intervjustudie med semistrukturerade frågor och induktiv ansatsgenomfördes. Tio ögonsjuksköterskor från fem ögonmottagningar i mellersta ochsödra Sverige deltog. Resultat: Analysen resulterade i tre kategorier och åttasubkategorier. De tre kategorierna var; Oro varierar, Omständigheter som kanpåverka oro, Oro kan leda till konsekvenser. Konklusion: Ögonsjuksköterskornahade en erfarenhet av att alla patienter hade någon form av oro preoperativt.Individanpassad information och ett personcentrerat omvårdnadsarbete var ett stöd föratt lindra oro hos patienterna. Teamets betydelse och specifika omvårdnadsåtgärdersom till exempel en hand att hålla var också av värde. Framtida studier kan varaintervjuer med ögonsjuksköterskor eller patienter med fokus på omvårdnadsåtgärdersom kan stilla oro.

Problemformulering: Behandling med intravitreala injektioner ökar och patienter som genomgår denna behandling upplever ofta oro och osäkerhet. Det finns behov att stärka och tydliggöra ögonsjuksköterskans roll i omvårdnaden runt patienter som får injektionsbehandling. Detta för att på bästa sätt värna om både patienten och den egna professionen. Syfte: Syftet var att belysa ögonsjuksköterskors upplevelser av att vårda patienter som behandlas med intravitreala injektioner. Metod: En intervjustudie med kvalitativ metod med semistrukturerade frågor och induktiv ansats genomfördes. Åtta ögonsjuksköterskor från fem ögonmottagningar i Mellansverige deltog i studien. Resultat: Analysen resulterade i fem kategorier och tio subkategorier. De fem kategorierna var; Ögonsjuksköterskans roll, Meningsfullt arbete, Patientperspektiv - ögonsjuksköterskornas upplevelser, Upplevda utmaningar och Betydelsefull utveckling. Konklusion: Ögonsjuksköterskorna upplevde sitt arbete meningsfullt och positivt, där de såg sig ha en viktig roll för patienterna. Den dagliga omvårdnaden blev dock inte alltid synlig och ögonsjuksköterskorna kunde ibland ha svårt att identifiera omvårdnaden de gav. Genom att utforma en lätthanterlig och tidseffektiv omvårdnadsdokumentation och individuell vårdplan kan ögonsjuksköterskans omvårdnad synliggöras vilket i sin tur kan möjliggöra patienternas delaktighet och stärka patientsäkerheten. Gruppinformation till patienter skulle också kunna vara ett led i utvecklingen. Förslag på vidare forskning är djupintervjuer med patienter och ögonsjuksköterskor för att undersöka hur vården skulle kunna utvecklas., Problem definition: Treatment with intravitreal injections is increasing and patients undergoing this treatment often experience anxiety and insecurity. There is a need to strengthen and clarify the ophthalmic nurse's role in the care of patients receiving injection treatment. This is to best protect both the patient and the ophthalmic nurse’s profession. Purpose: The purpose was to illustrate the ophthalmic nurses’ experiences of caring for patients being treated with intravitreal injections. Method: A qualitative interview study with semi-structured questions and an inductive approach was performed. Eight ophthalmic nurses from five ophthalmic clinics in Central Sweden participated in the study. Results: The analysis resulted in five categories and ten subcategories. The five categories were; The ophthalmic nurse's role, Meaningful work, Patient perspective - The ophthalmic nurses' experiences, Perceived challenges and Significant development. Conclusion: The ophthalmic nurses experienced their work meaningful and positively, where they saw themselves as having an important role for the patients. However, daily care did not always become visible and the ophthalmic nurses could sometimes find it difficult to identify the care they provided. By designing an easy-to-use and time-efficient nursing documentation and individual care plan, the ophthalmic nurse's nursing can be made visible, which in turn can enable patients' participation and strengthen patient safety. Group information to patients could also be part of the development. Suggestions for further research are in-depth interviews with patients and ophthalmic nurses to investigate how the care could be developed.

PurposeTo evaluate refractive and structural outcomes for patients treated for retinopathy of prematurity (ROP) with the anti-vascular endothelial growth factor (anti-VEGF) agent ranibizumab and "delayed laser," defined as any laser photocoagulation treatment administered at least 2 weeks and <1 year after the initial anti-VEGF injection.MethodsThe medical records of infants with type 1 ROP treated between 2015 and 2020 with intravitreal 0.25 mg ranibizumab followed by delayed laser photocoagulation, with a minimum of 6 months' follow-up, were reviewed retrospectively. Refractive and structural outcomes were extracted from the record.ResultsA total of 68 eyes of 34 neonates were included, with median gestational age of 24 weeks and birthweight of 657 g. Patients were aged 0.9 to 4.4 years at last follow-up; mean follow-up interval was 2.7 ± 1.02 years. There was no progression to stage 4 or 5 following treatment during the study period. At 2 years' follow-up (mean age, 2.41 ± 0.23 years), median spherical equivalent (SE) was -0.13 D (IQR, 4.20 D). At most recent examination (mean age, 2.70 ± 1.02 years), the most common ocular findings included strabismus (32%), optic atrophy (24%), amblyopia (21%), high myopia (7%), and nystagmus (4%).ConclusionsIn our small cohort, neonates with type 1 ROP treated with intravitreal ranibizumab and delayed laser demonstrated good structural outcomes, with no progression to retinal detachment. We found lower rates of high myopia compared with previous reports of laser photocoagulation monotherapy.

PURPOSE: To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration. DESIGN: Cohort within a randomized clinical trial. PARTICIPANTS: Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment. METHODS: The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the presence of IRF at the baseline and in ≥ 80% of follow-up visits. Among eyes with baseline IRF, the mean VA scores (letters) and changes from the baseline were compared between eyes with and those without PP-IRF. Adjusted mean VA scores and changes from the baseline were also calculated using the linear regression analysis to account for baseline patient features identified as predictors of VA in previous CATT studies. Furthermore, outcomes were adjusted for concomitant predominantly persistent subretinal fluid. MAIN OUTCOME MEASURES: Predominantly persistent intraretinal fluid through week 12, year 1, and year 2; VA score and VA change; and scar development at year 2. RESULTS: Among 363 eyes with baseline IRF, 108 (29.8%) had PP-IRF through year 1 and 95 (26.1%) had PP-IRF through year 2. When eyes with PP-IRF through year 1 were compared with those without PP-IRF, the mean 1-year VA score was 62.4 and 68.5, respectively (P = 0.002), and was 65.0 and 67.4, respectively (P = 0.13), after adjustment. Predominantly persistent intraretinal fluid through year 2 was associated with worse adjusted 1-year mean VA scores (64.8 vs. 69.2; P = 0.006) and change (4.3 vs. 8.1; P = 0.01) as well as worse adjusted 2-year mean VA scores (63.0 vs. 68.3; P&n

Problemformulering: Behandling med intravitreala injektioner ökar och patienter som genomgår denna behandling upplever ofta oro och osäkerhet. Det finns behov att stärka och tydliggöra ögonsjuksköterskans roll i omvårdnaden runt patienter som får injektionsbehandling. Detta för att på bästa sätt värna om både patienten och den egna professionen. Syfte: Syftet var att belysa ögonsjuksköterskors upplevelser av att vårda patienter som behandlas med intravitreala injektioner. Metod: En intervjustudie med kvalitativ metod med semistrukturerade frågor och induktiv ansats genomfördes. Åtta ögonsjuksköterskor från fem ögonmottagningar i Mellansverige deltog i studien. Resultat: Analysen resulterade i fem kategorier och tio subkategorier. De fem kategorierna var; Ögonsjuksköterskans roll, Meningsfullt arbete, Patientperspektiv - ögonsjuksköterskornas upplevelser, Upplevda utmaningar och Betydelsefull utveckling. Konklusion: Ögonsjuksköterskorna upplevde sitt arbete meningsfullt och positivt, där de såg sig ha en viktig roll för patienterna. Den dagliga omvårdnaden blev dock inte alltid synlig och ögonsjuksköterskorna kunde ibland ha svårt att identifiera omvårdnaden de gav. Genom att utforma en lätthanterlig och tidseffektiv omvårdnadsdokumentation och individuell vårdplan kan ögonsjuksköterskans omvårdnad synliggöras vilket i sin tur kan möjliggöra patienternas delaktighet och stärka patientsäkerheten. Gruppinformation till patienter skulle också kunna vara ett led i utvecklingen. Förslag på vidare forskning är djupintervjuer med patienter och ögonsjuksköterskor för att undersöka hur vården skulle kunna utvecklas., Problem definition: Treatment with intravitreal injections is increasing and patients undergoing this treatment often experience anxiety and insecurity. There is a need to strengthen and clarify the ophthalmic nurse's role in the care of patients receiving injection treatment. This is to best protect both the patient and the ophthalmic nurse’s profession. Purpose: The purpose was to illustrate the ophthalmic nurses’ experiences of caring for patients being treated with intravitreal injections. Method: A qualitative interview study with semi-structured questions and an inductive approach was performed. Eight ophthalmic nurses from five ophthalmic clinics in Central Sweden participated in the study. Results: The analysis resulted in five categories and ten subcategories. The five categories were; The ophthalmic nurse's role, Meaningful work, Patient perspective - The ophthalmic nurses' experiences, Perceived challenges and Significant development. Conclusion: The ophthalmic nurses experienced their work meaningful and positively, where they saw themselves as having an important role for the patients. However, daily care did not always become visible and the ophthalmic nurses could sometimes find it difficult to identify the care they provided. By designing an easy-to-use and time-efficient nursing documentation and individual care plan, the ophthalmic nurse's nursing can be made visible, which in turn can enable patients' participation and strengthen patient safety. Group information to patients could also be part of the development. Suggestions for further research are in-depth interviews with patients and ophthalmic nurses to investigate how the care could be developed.

Aim: To evaluate an intravitreally injected nanoparticle platform designed to deliver VEGF-A siRNA to inhibit retinal neovascular leakage as a new treatment for proliferative diabetic retinopathy and diabetic macular edema. Materials & methods: Fusogenic lipid-coated porous silicon nanoparticles loaded with VEGF-A siRNA, and pendant neovascular integrin-homing iRGD, were evaluated for efficacy by intravitreal injection in a rabbit model of retinal neovascularization. Results: For 12 weeks post-treatment, a reduction in vascular leakage was observed for treated diseased eyes versus control eyes (p = 0.0137), with a corresponding reduction in vitreous VEGF-A. Conclusion: Fusogenic lipid-coated porous silicon nanoparticles siRNA delivery provides persistent knockdown of VEGF-A and reduced leakage in a rabbit model of retinal neovascularization as a potential new intraocular therapeutic.

Purpose: retinal vein occlusion (RVO) is classified as either branch (BRVO) or central (CRVO) RVO. The gold standard treatment for macular oedema (MO) secondary to RVO is intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Our study aimed to compare ranibizumab and aflibercept outcomes over a maximum follow-up of five years. Methods: this retrospective study assessed treatment-naïve RVO patients. Active disease was treated with three loading injections followed by a pro-re-nata (PRN) regimen of an anti-VEGF agent. Visual outcomes and injection frequency were analyzed, with patients stratified according to RVO subtype, anti-VEGF agent used, baseline vision, and age. Results: 316 CRVO-affected eyes and 467 BRVO-affected eyes were analysed. Visual benefits between different treatments did not significantly differ, except in year 1 in ranibizumab-treated BRVO eyes. However, aflibercept-treated CRVO and BRVO eyes required significantly fewer injections during the follow up period. Furthermore, our results confirm that younger patients achieve better visual outcomes with fewer intravitreal injections. Overall, half of our patients did not require further injections after 1 year from diagnosis. Conclusion: the results demonstrate that anti-VEGF treatment of RVO benefits vision for up to 5 years. Our findings are the first to suggest that compared to ranibizumab, fewer aflibercept injections may be required over five years follow up. Prospective randomised trials are needed to confirm this, alongside further attention to OCT scan features and the effect of patient demographics on treatment outcomes.

PurposeWe aimed to investigate non-exudative microcystoid macular abnormalities for visual and anatomical outcome in patients with retinal vein occlusion (RVO) with and without glaucomatous optic neuropathy (GON).MethodsMedical records of 124 eyes (105 patients) with RVO were reviewed and analyzed. Eyes demonstrating microcystoid macular abnormalities were divided into 2 groups, those with evidence of glaucoma (group A) and those without glaucoma (group B). Best-corrected visual acuity (BCVA), the prevalence and number of microcystoid macular abnormalities, and number of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections were compared at baseline and follow-up.ResultsSeventy-one out of 105 eyes (67.6%) with RVO displayed microcystoid macular abnormalities. Thirty-eight out of 71 eyes (53.5%) presented with concomitant glaucoma (group A), while the remaining 33 eyes (42.6%) had no history of glaucoma (group B). At the end of the follow-up period, mean BCVA was worse in group A versus group B (20/80 versus 20/40, respectively; p = .003). The mean number of anti-VEGF injections was 10.1 ± 9.2 in group A versus 5.9 ± 6.9 in group B (p = .03).ConclusionEyes with RVO and concomitant glaucoma exhibited a significantly higher number of microcystoid macular abnormalities and worse BCVA versus eyes with RVO without glaucoma.

Neovascularization is a key feature of ischemic retinal diseases and the wet form of age-related macular degeneration (AMD), all leading causes of severe vision loss. Vascular endothelial growth factor (VEGF) inhibitors have transformed the treatment of these disorders. Millions of patients have been treated with these drugs worldwide. However, in real-life clinical settings, many patients do not experience the same degree of benefit observed in clinical trials, in part because they receive fewer anti-VEGF injections. Therefore, there is an urgent need to discover and identify novel long-acting VEGF inhibitors. We hypothesized that binding to heparan-sulfate proteoglycans (HSPG) in the vitreous, and possibly other ocular structures, may be a strategy to promote intraocular retention, ultimately leading to a reduced burden of intravitreal injections. We designed a series of VEGF receptor 1 variants and identified some with strong heparin-binding characteristics and ability to bind to vitreous matrix. Our data indicate that some of our variants have longer duration and greater efficacy in animal models of intraocular neovascularization than current standard of care. Our study represents a systematic attempt to exploit the functional diversity associated with heparin affinity of a VEGF receptor.

PurposeWe aimed to investigate non-exudative microcystoid macular abnormalities for visual and anatomical outcome in patients with retinal vein occlusion (RVO) with and without glaucomatous optic neuropathy (GON).MethodsMedical records of 124 eyes (105 patients) with RVO were reviewed and analyzed. Eyes demonstrating microcystoid macular abnormalities were divided into 2 groups, those with evidence of glaucoma (group A) and those without glaucoma (group B). Best-corrected visual acuity (BCVA), the prevalence and number of microcystoid macular abnormalities, and number of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections were compared at baseline and follow-up.ResultsSeventy-one out of 105 eyes (67.6%) with RVO displayed microcystoid macular abnormalities. Thirty-eight out of 71 eyes (53.5%) presented with concomitant glaucoma (group A), while the remaining 33 eyes (42.6%) had no history of glaucoma (group B). At the end of the follow-up period, mean BCVA was worse in group A versus group B (20/80 versus 20/40, respectively; p = .003). The mean number of anti-VEGF injections was 10.1 ± 9.2 in group A versus 5.9 ± 6.9 in group B (p = .03).ConclusionEyes with RVO and concomitant glaucoma exhibited a significantly higher number of microcystoid macular abnormalities and worse BCVA versus eyes with RVO without glaucoma.

PurposeTo identify clinical and anatomic factor-associated vision loss in eyes with treatment-naïve diabetic macular edema and good initial visual acuity.MethodsRetrospective cohort study after long-term history of eyes with untreated center-involving diabetic macular edema and baseline visual acuity ≥ 20/25 seen at the University of California, Davis Eye Center between March 2007 and March 2018. We collected characteristics including diabetes type, hemoglobin A1c, presence of visual symptoms, visual acuity, and diabetic retinopathy severity; and spectral-domain optical coherence tomography biomarkers including central subfield thickness, intraretinal cyst size, intraretinal hyperreflective foci, disorganization of retinal inner layers, and outer layer disruptions to determine factors associated with vision loss as defined by DRCR Protocol V as threshold for initiating aflibercept therapy.ResultsFifty-six eyes (48 patients) with untreated diabetic macular edema and mean baseline visual acuity of logMAR 0.05 ± 0.05 (Snellen 20/22) were followed for an average of 5.1 ± 3.3 years, with a median time to vision loss of 465 days (15 months). Older age (hazard ratio [HR] 1.04/year, P = 0.0195) and eyes with severe NPDR (HR 3.0, P = 0.0353) or proliferative diabetic retinopathy (HR 7.7, P = 0.0008) had a higher risk of a vision loss event. None of the spectral-domain optical coherence tomography biomarkers were associated with vision loss except central subfield thickness (HR 0.98, P = 0.0470) and cyst diameter (HR 1.0, P = 0.0094).ConclusionIn eyes with diabetic macular edema and good initial vision, those with older age and worse diabetic retinopathy severity should be monitored closely for prompt treatment initiation when vision loss occurs.

BACKGROUND: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials. METHODS: In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G>A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a period of up to 52 months after onset of vision loss. A locally estimated scatterplot smoothing regression model was used to analyze changes in BCVA over time. Vision-related quality of life was reported using the visual function questionnaire-25 (VFQ-25). RESULTS: The population of MT-ND4 subjects enrolled in RESTORE was representative of the combined cohorts of RESCUE and REVERSE for mean age (35.1 years) and gender distribution (79% males). There was a progressive and sustained improvement of BCVA up to 52 months after the onset of vision loss. The final mean BCVA was 1.26 logarithm of the minimal angle of resolution 48 months after the onset of vision loss. The mean VFQ-25 composite score increased by 7 points compared with baseline. CONCLUSION: The treatment effect of lenadogene nolparvovec on BCVA and vision-related quality of life observed 96 weeks (2 years) after treatment in RESCUE and REVERSE was sustained at 3 years in RESTORE, with a maximum follow-up of 52 months (4.3 years) after the onset of vision loss.

Vascular endothelial growth factor (VEGF) inhibition can cause worsening hypertension, proteinuria, chronic kidney injury, and glomerular disease. Thrombotic microangiopathy (TMA) and other nephrotic disorders have been reported with systemic VEGF blockade. These same agents are given intravitreally for age-related macular degeneration (AMD) and diabetic retinopathy (DR), albeit at lower doses than those given for systemic indications. Systemic absorption of anti-VEGF agents when given intravitreally has been shown consistently along with evidence of significant intravascular VEGF suppression. While worsening hypertension has only been seen in some large-scale studies, case reports show worsening proteinuria and diverse glomerular diseases. These include TMA-associated lesions like focal and segmental glomerulosclerosis with collapsing features (cFSGS). In this paper, we report three cases of TMA likely associated with the use of intravitreal anti-VEGF therapy. These patients developed the signature lesion of VEGF blockade in a 6 to 11 month time frame after starting intravitreal VEGF inhibitors. The literature is reviewed showing similar cases. Intravitreal VEGF blockade may cause these adverse events in a hitherto unidentified subgroup of patients. Well-controlled prospective observational trials are needed to determine the event rate and identify which subgroups of patients are at increased risk. A registry for patients who develop worsening hypertension, proteinuria exacerbation, and glomerular diseases from intravitreal VEGF blockade is proposed.

PrecisAt 1-year postoperative follow-up, concurrent placement of a dexamethasone intravitreal implant and glaucoma drainage device effectively controlled intraocular pressure (IOP) and inflammation in eyes with uveitic glaucoma with no changes in systemic immunomodulatory therapy.PurposeThe purpose of this study was to assess 1-year postoperative outcomes in eyes with uncontrolled uveitic glaucoma following concurrent placement of a dexamethasone intravitreal implant and glaucoma drainage device.Materials and methodsThis is a retrospective, observational case series of patients with chronic, noninfectious uveitis and uveitic glaucoma uncontrolled on maximal tolerated medical therapy with at least 1-year postoperative follow-up. The main outcomes were visual acuity, IOP, number of glaucoma medications, recurrent inflammation, frequency of topical steroids, systemic immunomodulatory therapy, and adverse events. Success was defined as IOP <21 mm Hg and IOP reduced by >20% from baseline on at least 2 consecutive visits after 3 months either with or without glaucoma medications (ie, partial or complete success, respectively).ResultsEight eyes in 6 patients met the inclusion criteria. The average age was 44.1±19.7 years (range: 10 to 68 y) and 50% were female. At 1-year, there was no significant change in visual acuity. No eyes lost ≥3 lines of vision. The majority of eyes (87.5%) achieved complete (n=2) or partial success (n=5) with a decrease in average IOP from 36.5 to 11.8 mm Hg (P=0.002). Glaucoma medication use decreased from 3.0 to 1.3 medications (P=0.04). There was a significant decrease in the number of episodes of recurrent inflammation in the 6 months following surgery compared with the 6 months before surgery (P=0.004).ConclusionIn this small case series, dexamethasone intravitreal implant combined with Ahmed glaucoma drainage device appears to be an effective approach for the management of uncontrolled uveitic glaucoma.

AimTo show the characteristics and outcomes of patients with neovascular age-related macular degeneration (nAMD) who had extended remission (ER) while on a pro re nata (PRN) treatment protocol.MethodsThis was a retrospective case-control study of a consecutive series of patients with nAMD treated with a PRN antivascular endothelial growth factor (anti-VEGF) drug regimen. ER was defined as the absence of haemorrhage, intraretinal/subretinal fluid on optical coherence tomography and leakage on fluorescein angiography for 52 weeks after cessation of anti-VEGF therapy. Matching patients with nAMD who did not achieve ER were included as control group. Cox regression analysis was fitted to identify predictors of time to achieve ER and time to recurrence. A logistic regression analysis of baseline characteristics was used to identify predictors of achieving ER.ResultsOf 830 eyes treated with anti-VEGF monotherapy, 77 (9.2%) eyes achieved ER during a median follow-up of 236 weeks (range 70-525 weeks). Cox regression analysis showed that ER was achieved earlier in eyes with isolated intraretinal fluid (HR, 2.05; 95% CI 1.929 to 4.520; p=0.045) at presentation. Logistic regression analysis showed that type 3 choroidal neovascularisation (OR, 0.090; 95% CI 0.021 to 0.382; p=0.001), thinner choroid (OR, 0.993; 95% CI 0.988 to 0.998; p=0.004) and absence of macular atrophy (OR, 0.233; 95% CI 0.065 to 0.839; p=0.026) at baseline increased the likelihood of achieving ER.ConclusionER is achievable in 9.2% of patients under PRN therapy for nAMD. At presentation with nAMD, anatomical features on retinal imaging may predict the likelihood of achieving ER and a shorter time to achieve ER.

Mesoporous silica has attracted significant attention in the drug delivery area; however, impurities can be a source of toxicity. The current study used commercial microparticles produced at large scale in a well-controlled environment. Micrometer sized mesoporous silica particles were acquired through a commercial vendor and pore structures were characterized by SEM. The three silica particle formulations had a diameter of 15 micrometers and three different pore sizes of 10 nm, 30 nm, and 100 nm. The fourth formulation had particle size of 20-40 micrometers with 50 nm pores. Before in vivo tests, an in vitro cytotoxicity test was conducted with silicic acid, derived from the sol-gel particles, on EA.hy926 cells. Low concentration (2.5 µg/mL) of silicic acid showed no cytotoxicity; however, high concentration (25 µg/mL) was cytotoxic. In vivo intravitreal injection demonstrated that 15 um silica particles with 10 nm pore were safe in both rabbit and guinea pig eyes and the particles lasted in the vitreous for longer than two months. Formulations of with larger pores demonstrated variable localized vitreous cloudiness around the sol-gel particle depot and mild inflammatory cells in the aqueous humor. The incidence of reaction trended higher with larger pores (10 nm: 0%, 30 nm: 29%, 50 nm: 71%, 100 nm: 100%, p < .0001, Cochran Armitage Trend Test). Sol-gel mesoporous silica particles have uniform particle sizes and well-defined pores, which is an advantage for implantation via a fine needle. Selected formulations may be used as an intraocular drug delivery system with proper loading and encapsulation.

Introduction: The migration of a dexamethasone implant to the anterior chamber is a vision-threatening complication which can happen in non-compartmentalized eyes treated with this device. Previous literature suggests that the solution to this complication is almost always surgical and in most cases cannot be delayed. Case description: We present the case of a 78-year-old woman with a scleral-fixated IOL and macular edema treated with Ozurdex. She came to us complaining of blurred vision and was subsequently diagnosed with an anterior-chamber migration of her dexamethasone implant. Postural manoeuvres were performed until the dexamethasone implant returned to the vitreous cavity through the pupil. Pilocarpine drops were prescribed with a positive outcome and no further migrations were described. Discussion: This case shows a practical and efficient way of managing a potentially vision-threatening complication without placing the patient onto an operating table. It is interesting to see how it is possible to relocate a dexamethasone implant despite the presence of a scleral-fixated IOL. Conclusion: Postural manoeuvres are an interesting option in patients with a dexamethasone implant migrated to the anterior chamber. This approach can have very positive outcomes, in addition to avoiding surgery, with all the risks and complications involved.

Introduction: The migration of a dexamethasone implant to the anterior chamber is a vision-threatening complication which can happen in non-compartmentalized eyes treated with this device. Previous literature suggests that the solution to this complication is almost always surgical and in most cases cannot be delayed. Case description: We present the case of a 78-year-old woman with a scleral-fixated IOL and macular edema treated with Ozurdex®. She came to us complaining of blurred vision and was subsequently diagnosed with an anterior-chamber migration of her dexamethasone implant. Postural manoeuvres were performed until the dexamethasone implant returned to the vitreous cavity through the pupil. Pilocarpine drops were prescribed with a positive outcome and no further migrations were described. Discussion: This case shows a practical and efficient way of managing a potentially vision-threatening complication without placing the patient onto an operating table. It is interesting to see how it is possible to relocate a dexamethasone implant despite the presence of a scleral-fixated IOL. Conclusion: Postural manoeuvres are an interesting option in patients with a dexamethasone implant migrated to the anterior chamber. This approach can have very positive outcomes, in addition to avoiding surgery, with all the risks and complications involved.

Introduction: The migration of a dexamethasone implant to the anterior chamber is a vision-threatening complication which can happen in non-compartmentalized eyes treated with this device. Previous literature suggests that the solution to this complication is almost always surgical and in most cases cannot be delayed. Case description: We present the case of a 78-year-old woman with a scleral-fixated IOL and macular edema treated with Ozurdex. She came to us complaining of blurred vision and was subsequently diagnosed with an anterior-chamber migration of her dexamethasone implant. Postural manoeuvres were performed until the dexamethasone implant returned to the vitreous cavity through the pupil. Pilocarpine drops were prescribed with a positive outcome and no further migrations were described. Discussion: This case shows a practical and efficient way of managing a potentially vision-threatening complication without placing the patient onto an operating table. It is interesting to see how it is possible to relocate a dexamethasone implant despite the presence of a scleral-fixated IOL. Conclusion: Postural manoeuvres are an interesting option in patients with a dexamethasone implant migrated to the anterior chamber. This approach can have very positive outcomes, in addition to avoiding surgery, with all the risks and complications involved.

INTRODUCTION: STELLAR was a Belgian, multicentre, retrospective, observational chart review that described the utilization (number of injections and treatment regimen) and effectiveness of intravitreal aflibercept (IVT-AFL) in patients with anti-vascular endothelial growth factor (VEGF) treatment-naïve neovascular age-related macular degeneration (nAMD) during the first 12 months of IVT-AFL treatment. METHODS: Patients initiating IVT-AFL between July 2013 and July 2017 were included in STELLAR. Primary endpoints were number of visits and IVT-AFL injections, and number of patients who received ≥ 7 versus < 7 IVT-AFL injections during the first 12 months of treatment. RESULTS: A total of 337 patients completed ≥ 12 months of IVT-AFL treatment. The mean number of visits and mean number of injections during the first 12 months was 9.8 and 7.1 injections, respectively (64% received ≥ 7 injections). Overall, 96% of patients received ≥ 3 initial monthly injections. Of the 337 patients, 180 received VT-AFL as needed (pro re nata), 141 received it as treat-and-extend dosing and 16 received it as fixed dosing. The proportion of patients who received treat-and-extend dosing increased year-on-year. Mean best-corrected visual acuity (BCVA) (± standard deviation) was 61.6 (± 14.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline and improved by + 3.9 and + 5.7 ETDRS letters at 3 and 12 months, respectively. Mean BCVA improvement was numerically greater in patients who received ≥ 7 versus < 7 injections during the first 12 months 7 (+ 6.5 vs. + 4.4 ETDRS letters) and in patients who received ≥ 3 versus < 3 initial monthly injections (+ 5.2 vs. - 0.25 ETDRS letters [3 at months]; + 5.9 vs + 1.2 ETDRS letters [at 12 months]). No specific adverse events were reported. CONCLUSION: Most patients in this Belgian study received ≥ 7 IVT-AFL injections during a mean of 9.8 visits over the 12 months assessed. IVT-AFL was an effective treatment for nAMD in clinical prac

PrecisAt 1-year postoperative follow-up, concurrent placement of a dexamethasone intravitreal implant and glaucoma drainage device effectively controlled intraocular pressure (IOP) and inflammation in eyes with uveitic glaucoma with no changes in systemic immunomodulatory therapy.PurposeThe purpose of this study was to assess 1-year postoperative outcomes in eyes with uncontrolled uveitic glaucoma following concurrent placement of a dexamethasone intravitreal implant and glaucoma drainage device.Materials and methodsThis is a retrospective, observational case series of patients with chronic, noninfectious uveitis and uveitic glaucoma uncontrolled on maximal tolerated medical therapy with at least 1-year postoperative follow-up. The main outcomes were visual acuity, IOP, number of glaucoma medications, recurrent inflammation, frequency of topical steroids, systemic immunomodulatory therapy, and adverse events. Success was defined as IOP <21 mm Hg and IOP reduced by >20% from baseline on at least 2 consecutive visits after 3 months either with or without glaucoma medications (ie, partial or complete success, respectively).ResultsEight eyes in 6 patients met the inclusion criteria. The average age was 44.1±19.7 years (range: 10 to 68 y) and 50% were female. At 1-year, there was no significant change in visual acuity. No eyes lost ≥3 lines of vision. The majority of eyes (87.5%) achieved complete (n=2) or partial success (n=5) with a decrease in average IOP from 36.5 to 11.8 mm Hg (P=0.002). Glaucoma medication use decreased from 3.0 to 1.3 medications (P=0.04). There was a significant decrease in the number of episodes of recurrent inflammation in the 6 months following surgery compared with the 6 months before surgery (P=0.004).ConclusionIn this small case series, dexamethasone intravitreal implant combined with Ahmed glaucoma drainage device appears to be an effective approach for the management of uncontrolled uveitic glaucoma.

Mesoporous silica has attracted significant attention in the drug delivery area; however, impurities can be a source of toxicity. The current study used commercial microparticles produced at large scale in a well-controlled environment. Micrometer sized mesoporous silica particles were acquired through a commercial vendor and pore structures were characterized by SEM. The three silica particle formulations had a diameter of 15 micrometers and three different pore sizes of 10 nm, 30 nm, and 100 nm. The fourth formulation had particle size of 20-40 micrometers with 50 nm pores. Before in vivo tests, an in vitro cytotoxicity test was conducted with silicic acid, derived from the sol-gel particles, on EA.hy926 cells. Low concentration (2.5 µg/mL) of silicic acid showed no cytotoxicity; however, high concentration (25 µg/mL) was cytotoxic. In vivo intravitreal injection demonstrated that 15 um silica particles with 10 nm pore were safe in both rabbit and guinea pig eyes and the particles lasted in the vitreous for longer than two months. Formulations of with larger pores demonstrated variable localized vitreous cloudiness around the sol-gel particle depot and mild inflammatory cells in the aqueous humor. The incidence of reaction trended higher with larger pores (10 nm: 0%, 30 nm: 29%, 50 nm: 71%, 100 nm: 100%, p < .0001, Cochran Armitage Trend Test). Sol-gel mesoporous silica particles have uniform particle sizes and well-defined pores, which is an advantage for implantation via a fine needle. Selected formulations may be used as an intraocular drug delivery system with proper loading and encapsulation.

Proliferative vitreoretinopathy (PVR) is a significant threat for vision recovery from retinal detachment or ocular trauma. Currently, no approved pharmacological intervention to prevent PVR. Daunorubicin (DNR) and dexamethasone (DEX) were sequentially loaded into oxidized porous silicon (pSiO2) particles by covalent conjugation. The DNR + DEX-loaded particles, and control particles loaded with DNR only and DEX only were incubated with RPE-populated collagen for daily gel surface quantitation. Toxicity was monitored by ophthalmic examinations and histological evaluation 21 days after injection. At 3rd week following intravitreal injection, a localized retinal detachment (RD) was created by subretinal injection of Healon in all pretreated eyes in addition to 3 non-interventional control eyes. 10 µg of bromodeoxyuridine (BrdU) was injected into the vitreous 4 h before sacrifice on day 3 after RD induction. Retinal sections were stained for glial fibrillary green protein (GFAP) and BrdU to identify activated glial cells and retinal cell proliferation. The studies demonstrated that all three pSiO2 particle types were well tolerated in vivo. DNR alone and DNR + DEX combination formulations demonstrated equally strong suppression on gel contraction (least square mean area of the gel: control = 1.71 vs. 30DNR = 1.85 or 30/40Dual = 1.83, p < .05). Eyes pretreated with pSiO2-DNR + DEX exhibited the least GFAP activation (least square mean intensity mm-2: Dual = 4.03, DNR = 7.76, Dex = 16.23, control = 29.11, p < .05) and BrdU expression (Mean number of BrdU positive cells per mm of retina: Dual = 2.77, DNR = 4.58, Dex = 4.01, control = 6.16, p < .05). The synergistic effect of a sustained release pSiO2-DNR/DEX showed promise for the prevention of PVR development while reducing the necessary therapeutic concentration of each drug.

Vascular endothelial growth factor (VEGF) inhibition can cause worsening hypertension, proteinuria, chronic kidney injury, and glomerular disease. Thrombotic microangiopathy (TMA) and other nephrotic disorders have been reported with systemic VEGF blockade. These same agents are given intravitreally for age-related macular degeneration (AMD) and diabetic retinopathy (DR), albeit at lower doses than those given for systemic indications. Systemic absorption of anti-VEGF agents when given intravitreally has been shown consistently along with evidence of significant intravascular VEGF suppression. While worsening hypertension has only been seen in some large-scale studies, case reports show worsening proteinuria and diverse glomerular diseases. These include TMA-associated lesions like focal and segmental glomerulosclerosis with collapsing features (cFSGS). In this paper, we report three cases of TMA likely associated with the use of intravitreal anti-VEGF therapy. These patients developed the signature lesion of VEGF blockade in a 6 to 11 month time frame after starting intravitreal VEGF inhibitors. The literature is reviewed showing similar cases. Intravitreal VEGF blockade may cause these adverse events in a hitherto unidentified subgroup of patients. Well-controlled prospective observational trials are needed to determine the event rate and identify which subgroups of patients are at increased risk. A registry for patients who develop worsening hypertension, proteinuria exacerbation, and glomerular diseases from intravitreal VEGF blockade is proposed.

PurposeTo analyse the intraocular pressure rise after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations.MethodsThe medical charts of 294 dexamethasone implants between February 2011 and 2017 were reviewed retrospectively. South Asian (India), White (Europe, US and Israel) Latino (Argentina and Brazil) patient data was included in the study. Ocular hypertension (OHT) was defined as intraocular pressure of >25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were diabetic macular edema (ME) (65.6%), retinal vein occlusion (26.5%), uveitis (7.8%).ResultsAmongst 294 intravitreal implants, ocular hypertension (>25 mmHg) was recorded in 0, 8 and 9.5% in White, Latino, and South Asian groups, respectively. However, IOP > 20 mmHg was recorded in 14%, 28% and 27% in White, Latino, and South Asian groups, respectively. Incidence of very high IOP (>35 mmHg) was lower in all geographical groups. It was 3% in Latino followed by 2% in South Asian group.ConclusionLatino and South Asian groups have higher IOP rise compared to White population. Most patients with elevated IOP fluctuate between 20-25 mmHg.

AimTo show the characteristics and outcomes of patients with neovascular age-related macular degeneration (nAMD) who had extended remission (ER) while on a pro re nata (PRN) treatment protocol.MethodsThis was a retrospective case-control study of a consecutive series of patients with nAMD treated with a PRN antivascular endothelial growth factor (anti-VEGF) drug regimen. ER was defined as the absence of haemorrhage, intraretinal/subretinal fluid on optical coherence tomography and leakage on fluorescein angiography for 52 weeks after cessation of anti-VEGF therapy. Matching patients with nAMD who did not achieve ER were included as control group. Cox regression analysis was fitted to identify predictors of time to achieve ER and time to recurrence. A logistic regression analysis of baseline characteristics was used to identify predictors of achieving ER.ResultsOf 830 eyes treated with anti-VEGF monotherapy, 77 (9.2%) eyes achieved ER during a median follow-up of 236 weeks (range 70-525 weeks). Cox regression analysis showed that ER was achieved earlier in eyes with isolated intraretinal fluid (HR, 2.05; 95% CI 1.929 to 4.520; p=0.045) at presentation. Logistic regression analysis showed that type 3 choroidal neovascularisation (OR, 0.090; 95% CI 0.021 to 0.382; p=0.001), thinner choroid (OR, 0.993; 95% CI 0.988 to 0.998; p=0.004) and absence of macular atrophy (OR, 0.233; 95% CI 0.065 to 0.839; p=0.026) at baseline increased the likelihood of achieving ER.ConclusionER is achievable in 9.2% of patients under PRN therapy for nAMD. At presentation with nAMD, anatomical features on retinal imaging may predict the likelihood of achieving ER and a shorter time to achieve ER.

Background/objectiveTo determine if treatment of exudative age-related macular degeneration (eAMD) using proton beam therapy (PBT) combined with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is safe and effective long term.Subject/methodsThirty eyes with newly diagnosed eAMD were enrolled in a phase I/II prospective, sham-controlled double-masked university study. Eyes were randomized 1:1:1-24 GyE, 16 GyE or sham radiation, and treated with three initial monthly intravitreal ranibizumab or bevacizumab. Subsequent anti-VEGF reinjection was based on monthly optical coherence tomography and examination for 2 years and standard of care thereafter.ResultsA total of 23 eyes completed 2-year study follow-up, of which 16 maintained monthly follow-up. Mean best-correct visual acuity (BCVA) at 2 years was similar among treatment groups (p > 0.05). The 24 GyE group required fewer anti-VEGF injections when compared with the sham group at 2 years (4.67 ± 1.9 vs 9.67 ± 3.5; p = 0.017). Extended follow-up (mean 4 years) available in 22 eyes showed persistent reduced need for anti-VEGF therapy among eyes treated with 24 GyE compared with sham radiation (2.0 ± 1.6 vs 4.84 ± 2.4 per year, p = 0.008). New and increasing geographic atrophy (GA), noted in some eyes in all treatment groups, resulted in decreased mean BCVA from baseline for the 24 GyE group on extended follow-up (p = 0.009). Possible mild radiation retinopathy noted in 15% of eyes was not visually significant.ConclusionsInitial treatment combining PBT (24 GyE) with intravitreal anti-VEGF therapy appears to decrease the need for anti-VEGF reinjection in eyes with newly diagnosed eAMD. Radiation retinopathy risk was low and does not appear visually significant. Long-term vision was limited by GA development especially in the 24 GyE group.

Human CD34 + stem cells are mobilized from bone marrow to sites of tissue ischemia and play an important role in tissue revascularization. This study used a murine model to test the hypothesis that intravitreal injection of human CD34 + stem cells harvested from bone marrow (BMSCs) can have protective effects in eyes with diabetic retinopathy. Streptozotocin-induced diabetic mice (C57BL/6J) were used as a model for diabetic retinopathy. Subcutaneous implantation of Alzet pump, loaded with Tacrolimus and Rapamycin, 5 days prior to intravitreal injection provided continuous systemic immunosuppression for the study duration to avoid rejection of human cells. Human CD34 + BMSCs were harvested from the mononuclear cell fraction of bone marrow from a healthy donor using magnetic beads. The CD34 + cells were labeled with enhanced green fluorescent protein (EGFP) using a lentiviral vector. The right eye of each mouse received an intravitreal injection of 50,000 EGFP-labeled CD34 + BMSCs or phosphate buffered saline (PBS). Simultaneous multimodal in vivo retinal imaging system consisting of fluorescent scanning laser ophthalmoscopy (enabling fluorescein angiography), optical coherence tomography (OCT) and OCT angiography was used to confirm the development of diabetic retinopathy and study the in vivo migration of the EGFP-labeled CD34 + BMSCs in the vitreous and retina following intravitreal injection. After imaging, the mice were euthanized, and the eyes were removed for immunohistochemistry. In addition, microarray analysis of the retina and retinal flat mount analysis of retinal vasculature were performed. The development of retinal microvascular changes consistent with diabetic retinopathy was visualized using fluorescein angiography and OCT angiography between 5 and 6 months after induction of diabetes in all diabetic mice. These retinal microvascular changes include areas of capillary nonperfusion and late leakage of fluorescein dye. Multimodal in vivo imaging and imm

PurposeTo evaluate spectral-domain (SD)-OCT features associated with baseline vision and visual outcomes in the prospective, multicenter Study Evaluating Dosing Regimens for Treatment with Intravitreal Ranibizumab Injections in Subjects with Macular Edema following Retinal Vein Occlusion (SHORE).DesignPost hoc analysis of prospective clinical trial data.ParticipantsTwo hundred two participants in the 15-month, phase 4 SHORE study comparing monthly versus pro re nata ranibizumab after 7 monthly doses in eyes with retinal vein occlusion (RVO) with macular edema.MethodsBaseline SD-OCT images were assessed for (1) central subfield thickness (CST); (2) presence of vitreomacular adhesion, vitreomacular traction, or epiretinal membrane; (3) presence, location, and amount of intraretinal fluid or subretinal fluid (SRF); (4) presence, location, and amount of hyperreflective foci (HF); (5) disorganization of retinal inner layers (DRIL); and (6) disruption of external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). Univariate and multivariate regression analyses were performed to evaluate the association of these features with baseline best-corrected visual acuity (BCVA) and change in BCVA after 7 monthly ranibizumab injections.Main outcome measuresAssociation of SD-OCT features with baseline BCVA and change in BCVA after 7 monthly ranibizumab injections.ResultsBefore therapy, worse baseline BCVA was associated with ERM presence (P = 0.0045), thicker SRF (P = 0.0006), larger intraretinal cysts (P = 0.0015), and higher percentage of DRIL (P < 0.0001), percentage of ELM disruption (P < 0.0001), percentage of EZ disruption (P = 0.0003), and percentage of IZ disruption (P = 0.0018). In multivariate models, only percentage of ELM disruption independently impacted baseline BCVA (P < 0.0001). After 7 monthly ranibizumab injections, mean BCVA improved by 18.3±12.6 Early Treatment Diabetic Retinopathy Study letters in treat

PURPOSE: To analyse the intraocular pressure rise after intravitreal dexamethasone implant (Ozurdex) amongst different geographic populations. METHODS: The medical charts of 294 dexamethasone implants between February 2011 and 2017 were reviewed retrospectively. South Asian (India), White (Europe, US and Israel) Latino (Argentina and Brazil) patient data was included in the study. Ocular hypertension (OHT) was defined as intraocular pressure of >25 mmHg or an increase of at least 10 mmHg from baseline. The main indications for treatment were diabetic macular edema (ME) (65.6%), retinal vein occlusion (26.5%), uveitis (7.8%). RESULTS: Amongst 294 intravitreal implants, ocular hypertension (>25 mmHg) was recorded in 0, 8 and 9.5% in White, Latino, and South Asian groups, respectively. However, IOP > 20 mmHg was recorded in 14%, 28% and 27% in White, Latino, and South Asian groups, respectively. Incidence of very high IOP (>35 mmHg) was lower in all geographical groups. It was 3% in Latino followed by 2% in South Asian group. CONCLUSION: Latino and South Asian groups have higher IOP rise compared to White population. Most patients with elevated IOP fluctuate between 20-25 mmHg.

Introduction: The migration of a dexamethasone implant to the anterior chamber is a vision-threatening complication which can happen in non-compartmentalized eyes treated with this device. Previous literature suggests that the solution to this complication is almost always surgical and in most cases cannot be delayed. Case description: We present the case of a 78-year-old woman with a scleral-fixated IOL and macular edema treated with Ozurdex. She came to us complaining of blurred vision and was subsequently diagnosed with an anterior-chamber migration of her dexamethasone implant. Postural manoeuvres were performed until the dexamethasone implant returned to the vitreous cavity through the pupil. Pilocarpine drops were prescribed with a positive outcome and no further migrations were described. Discussion: This case shows a practical and efficient way of managing a potentially vision-threatening complication without placing the patient onto an operating table. It is interesting to see how it is possible to relocate a dexamethasone implant despite the presence of a scleral-fixated IOL. Conclusion: Postural manoeuvres are an interesting option in patients with a dexamethasone implant migrated to the anterior chamber. This approach can have very positive outcomes, in addition to avoiding surgery, with all the risks and complications involved.

Recombinant adeno-associated virus (rAAV) has been widely used for gene delivery in animal models and successfully applied in clinical trials for treating inherited retinal disease. Although subretinal delivery of AAVs can effectively transduce photoreceptors and/or retinal pigmental epithelium (RPE), cells most affected by inherited retinal diseases, the procedure is invasive and complicated, and only delivers the gene to a limited retinal area. AAVs can also be delivered intravitreally to the retina, a much less invasive nonsurgical procedure. However, intravitreal administration of non-modified AAV serotypes tends to transduce only ganglion cells and inner nuclear layer cells. To date, most non-modified AAV serotypes that have been identified are incapable of efficiently transducing photoreceptors and/or RPE when delivered intravitreally. In this study, we investigate the retinal tropism of AAVrh10 vector administered by intravitreal injection to mouse, rat, and rabbit eyes. Our results demonstrate that AAVrh10 is capable of transducing not only inner retinal cells, but also outer retinal cells in all three species, though the transduction efficiency in rabbit was low. In addition, AAVrh10 preferentially transduced outer retinal cells in mouse models of retinal disease. Therefore, AAVrh10 vector could be a useful candidate to intravitreally deliver genes to photoreceptor and RPE cells.

Inherited and age-related retinal degenerative diseases cause progressive loss of rod and cone photoreceptors, leading to blindness, but spare downstream retinal neurons, which can be targeted for optogenetic therapy. However, optogenetic approaches have been limited by either low light sensitivity or slow kinetics, and lack adaptation to changes in ambient light, and not been shown to restore object vision. We find that the vertebrate medium wavelength cone opsin (MW-opsin) overcomes these limitations and supports vision in dim light. MW-opsin enables an otherwise blind retinitis pigmenotosa mouse to discriminate temporal and spatial light patterns displayed on a standard LCD computer tablet, displays adaption to changes in ambient light, and restores open-field novel object exploration under incidental room light. By contrast, rhodopsin, which is similar in sensitivity but slower in light response and has greater rundown, fails these tests. Thus, MW-opsin provides the speed, sensitivity and adaptation needed to restore patterned vision.

Purpose: We report a case of polycythemia with an ocular complication of branch retinal vein occlusion associated with macular edema that was managed by anti-vascular endothelial growth factor (VEGF) and systemic management.Methods: A 43-year-old, one-eyed male, a known case of polycythemia presented with complaints of decreased vision in the right eye. He underwent comprehensive eye evaluation, fundus photography and optical coherence tomography at the baseline visit and post intravitreal ranibizumab 1-, 3-, 4- and 11-month follow-up. Results: A patient with polycythaemia was diagnosed in the right eye with superotemporal branch retinal vein occlusion and macular edema, which clinically and on optical coherence tomography resolved after 1 intravitreal injection of ranibizumab. However, as he discontinued systemic management, macular edema reappeared and the edema resolved well after intravitreal ranibizumab. He then became more compliant to the systemic therapy and was asymptomatic for the last 7 months. Conclusion: In a case of retinal vein occlusion with macular edema of recognizable cause, the management of systemic disease and anti-VEGF can give satisfactory results.

Inherited and age-related retinal degenerative diseases cause progressive loss of rod and cone photoreceptors, leading to blindness, but spare downstream retinal neurons, which can be targeted for optogenetic therapy. However, optogenetic approaches have been limited by either low light sensitivity or slow kinetics, and lack adaptation to changes in ambient light, and not been shown to restore object vision. We find that the vertebrate medium wavelength cone opsin (MW-opsin) overcomes these limitations and supports vision in dim light. MW-opsin enables an otherwise blind retinitis pigmenotosa mouse to discriminate temporal and spatial light patterns displayed on a standard LCD computer tablet, displays adaption to changes in ambient light, and restores open-field novel object exploration under incidental room light. By contrast, rhodopsin, which is similar in sensitivity but slower in light response and has greater rundown, fails these tests. Thus, MW-opsin provides the speed, sensitivity and adaptation needed to restore patterned vision.

PurposeTo test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy.DesignRandomized sham-controlled clinical trial.ParticipantsNinety-nine study eyes of 67 eligible participants were enrolled.MethodsSingle-masked randomized clinical trial of 24 months' duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a sham procedure.Main outcome measuresThe primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral-domain (SD) OCT images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups.ResultsAmong the 67 participants who were randomized (mean age, 62±8.9 years; 41 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 participants (4 eyes) were found ineligible. The eyes receiving sham treatment had 31% greater progression of neurodegeneration than the CNTF-treated eyes. The difference in mean area of photoreceptor loss was 0.05±0.03 mm2 (P = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly with the changes in the area of photoreceptor loss (r = 0.86; P < 0.0001). The mean retinal sensitivity loss of the sham group was 45% greater than that of the treated group (decrease, 15.81±8.93 dB; P = 0.07). Reading speed deteriorated in the sham group (-13.9 words per minute) with no loss in the treated group (P = 0.02). Serious adverse ocular effects were found in 2 of 51 pers

The Joslin Medalist Study characterized people affected with type 1 diabetes for 50 years or longer. More than 35% of these individuals exhibit no to mild diabetic retinopathy (DR), independent of glycemic control, suggesting the presence of endogenous protective factors against DR in a subpopulation of patients. Proteomic analysis of retina and vitreous identified retinol binding protein 3 (RBP3), a retinol transport protein secreted mainly by the photoreceptors, as elevated in Medalist patients protected from advanced DR. Mass spectrometry and protein expression analysis identified an inverse association between vitreous RBP3 concentration and DR severity. Intravitreal injection and photoreceptor-specific overexpression of RBP3 in rodents inhibited the detrimental effects of vascular endothelial growth factor (VEGF). Mechanistically, our results showed that recombinant RBP3 exerted the therapeutic effects by binding and inhibiting VEGF receptor tyrosine phosphorylation. In addition, by binding to glucose transporter 1 (GLUT1) and decreasing glucose uptake, RBP3 blocked the detrimental effects of hyperglycemia in inducing inflammatory cytokines in retinal endothelial and Müller cells. Elevated expression of photoreceptor-secreted RBP3 may have a role in protection against the progression of DR due to hyperglycemia by inhibiting glucose uptake via GLUT1 and decreasing the expression of inflammatory cytokines and VEGF.

PurposeTo evaluate the comparative effectiveness of 3 regional corticosteroid injections for uveitic macular edema (ME): periocular triamcinolone acetonide (PTA), intravitreal triamcinolone acetonide (ITA), and the intravitreal dexamethasone implant (IDI).DesignMulticenter, randomized clinical trial.ParticipantsPatients with uveitic ME.MethodsPatients were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME were assigned the same treatment for both eyes.Main outcome measuresThe primary outcome was the proportion of baseline (PropBL) central subfield thickness (CST) at 8 weeks (CST at 8 weeks/CST at baseline) assessed with OCT by masked readers. Secondary outcomes included ≥20% improvement and resolution of ME, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) events over 24 weeks.ResultsAll treatment groups demonstrated improved CST during follow-up. At 8 weeks, each group had clinically meaningful reductions in CST relative to baseline (PropBL: 0.77, 0.61, and 0.54, respectively, which translates to reductions of 23%, 39%, and 46% for PTA, ITA, and IDI, respectively). Intravitreal triamcinolone acetonide (PropBL ITA/PropBL PTA, hazard ratio [HR], 0.79; 99.87% confidence interval [CI], 0.65-0.96) and IDI (PropBL IDI/PropBL PTA, HR, 0.69; 99.87% CI, 0.56-0.86) had larger reductions in CST than PTA (P < 0.0001). Intravitreal dexamethasone implant was noninferior to ITA at 8 weeks (PropBL IDI/PropBL ITA, HR, 0.88; 99.87% CI, 0.71-1.08). Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic ME. All treatment groups demonstrated BCVA improvement throughout follow-up. Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than in the PTA group at 8 weeks (P < 0.004). The risk of having IOP ≥24 mmHg was higher in the intravitreal treatment groups compared with the periocular group (HR, 1.83; 95% CI, 0.91-3.65 and HR, 2.52; 95% CI, 1.29-4.91 for ITA and IDI, re