POLYPOIDAL LESIONS ASSOCIATED WITH CHOROIDAL NEVI.

PURPOSE: To investigate eyes with polypoidal lesions associated with choroidal nevi, their multimodal imaging characteristics, and long clinical follow-up. METHODS: Multicenter, retrospective case series study of patients with polypoidal lesions overlying choroidal nevi. Demographic and clinical information were recorded. Multimodal imaging including color fundus photography, optical coherence tomography, optical coherence tomography angiography, fundus fluorescein angiography, indocyanine angiography, and A- and B-scan ultrasonography were analyzed for nevus and polypoidal lesion characteristics. RESULTS: Fourteen eyes (14 patients; mean age: 70.3 ± 6.7 years) with polypoidal lesions overlying choroidal nevi were included. The mean follow-up duration was 50.0 ± 27.9 months (range 12-108). All nevi were pigmented on color fundus photography, flat on ultrasonography with a mean basal diameter of 3.8 ± 0.4 mm. In all but one eye, optical coherence tomography showed a shallow irregular pigment epithelium detachment overlying the nevus. A total of 11/14 eyes (78.6%) had exudative activity, 9 eyes received intravitreal anti-vascular endothelial growth factor injections, and one eye required intravitreal anti-vascular endothelial growth factor combined with photodynamic therapy. Mean visual acuity was 20/32 at baseline and 20/50 at final visit. CONCLUSION: We present the largest known cohort of eyes with polypoidal lesions associated with choroidal nevi with up to 9 years follow-up. The exudative degree of the polypoidal lesion in this condition is variable and treatment decisions should be taken on an individual basis. We hypothesize that choroidal ischemia because of altered choroidal vasculature rather than Haller layer hyperpermeability plays a role in the formation of polypoidal lesions overlying nevi.

Ocular Behçet Disease-Clinical Manifestations, Treatments and Outcomes According to Age at Disease Onset.

Behçet disease (BD) is a multisystemic disease that commonly involves the eyes. Although it affects patients in all age groups, data on ocular disease by age of onset are limited. This retrospective, multicenter study aimed to compare epidemiology, systemic and ocular manifestations, treatments and outcomes between three age groups: juvenile (<18 years), adult (18-39 years) and late (≥40 years) disease onset. The study included 175 ocular BD patients (303 eyes) from Israel and Palestine: juvenile-onset (n = 25, 14.3%), adult-onset (n = 120, 68.6%) and late-onset (n = 30, 17.1%). Most patients in all groups were male. Systemic manifestations were similar in all groups. Systemic co-morbidities were more common in late-onset patients. Bilateral panuveitis was the most common ocular manifestation in all patients. Non-occlusive retinal vasculitis, peripheral vessel occlusions, cataract and elevated intraocular pressure were found more commonly among juvenile-onset eyes. Anterior uveitis and macular ischemia were most common among late-onset eyes, while branch retinal vein occlusion was most common in adult and late-onset eyes. All patients were treated with corticosteroids. Methotrexate, immunomodulatory combinations and biologic treatments were more commonly used for juvenile-onset patients. All groups had a similar visual outcome. Our study showed that patients with ocular BD have varied ocular manifestations and require different treatments according to age of disease onset, but visual outcome is similar.

Retinal vascular occlusions in ocular Behçet disease - a comparative analysis.

PURPOSE: The literature on retinal vascular occlusions in Behçet disease (BD) patients is limited. The aim of this study is to thoroughly investigate retinal vascular occlusions among ocular BD patients. METHODS: Retrospective, multicentre case-control study. Three-hundred and three eyes of 175 patients with ocular BD, from 13 hospitals in Israel and Palestine, were included. Patients were assigned into two groups according to the presence of retinal vascular occlusion. Epidemiology, systemic and ocular manifestations, treatments and outcomes were compared between the groups and risk factors for retinal vascular occlusions were identified. RESULTS: One hundred twenty-five patients (71.4%) were male. The mean age at presentation was 28.2 ± 0.86 years. Retinal vascular occlusions were found in 80 eyes of 54 (30.9%) patients, including branch retinal vein occlusion (51.3%), peripheral vessels occlusions (32.5%), central retinal vein occlusion (13.8%) and arterial occlusions (7.5%). Systemic manifestations were similar among both groups. Anterior uveitis was more common in non-occlusive eyes (p < 0.01). Non-occlusive retinal vasculitis (p = 0.03) and ocular complications were more common in occlusive eyes (p < 0.01). Treatments including mycophenolate mofetil, Infliximab or a combination therapy of anti-metabolite and calcineurin inhibitor were more commonly used by occlusive patients (p < 0.05). Occlusive patients underwent more cataract surgeries (p = 0.03). The occlusive group had worse mean best-corrected visual acuity (BCVA) throughout follow-up (p < 0.01). Risk factors for retinal vascular occlusions included male sex and Jewish ethnicity (p < 0.05). CONCLUSION: Retinal vascular occlusions were found in a third of ocular BD patients. Occlusive eyes had a worse prognosis. Risk factors for vascular occlusions were identified.

Incidence and Risk Factors of Visual Impairment in Patients with Angioid Streaks and Macular Neovascularization.

OBJECTIVE: To estimate the incidence and risk factors of visual impairment and complications in eyes with macular neovascularization (MNV) because of angioid streaks (ASs). DESIGN: Longitudinal multicenter retrospective cohort study. SUBJECTS: Patients with AS-associated MNV treated with anti-VEGF agents and a follow-up of > 3 months. METHODS: Clinical and MNV characteristics were collected at baseline. Visual acuity (VA) values and the presence of atrophy or fibrosis were collected at each visit. MAIN OUTCOME MEASURES: Rate of VA change over time and associated factors; the incidence rate of moderate-to-severe visual impairment (MSVI) and blindness and hazard ratio (HR) of candidate risk factors for MSVI; the incidence rate of fibrosis and macular atrophy. RESULTS: Overall, 84 eyes of 66 patients (39 men, 58%) with a mean (standard deviation) age of 55.7 (13.8) years were followed for a mean (standard deviation) of 67.7 (48.5) months. The median number of anti-VEGF doses per eye was 13. The average rate (95% confidence interval [CI]) of visual loss was +0.04 (0.02-0.06) logarithm of the minimum angle of resolution/year (P < 0.001); the visual loss was faster in nonnaive eyes (P = 0.007) and those with better baseline VA (P < 0.001); it was slower in eyes with pattern dystrophy-like features (P = 0.04). The incidence rates (95% CI) of MSVI and blindness were 10.4 (6.88-15)/100-eye-years and 2.33 (1.12-4.29)/100-eye-years. A higher number of injections (HR [95% CI] = 0.45 [0.19-0.94] for receiving ≥ 13 injections vs. < 13; P = 0.03) was protective against MSVI. The incidence rates (95% CI) of fibrosis and macular atrophy were 24.1 (17.5-32.3)/100-eye-years and 14.3 (10.1-19.6)/100-eye-years. CONCLUSIONS: Eyes with MNV-related AS had a high rate of visual impairment and propensity to macular fibrosis and atrophy. A higher number of injections yielded better chances of maintaining good VA, suggesting the need for intensive treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Half-Dose Photodynamic Therapy as a Novel Treatment Protocol for Circumscribed Choroidal Hemangioma.

We present a case series of four patients with circumscribed choroidal hemangioma (CCH) treated with half-dose PDT, proposing this as a novel treatment protocol. Four patients with CCH were included, and then evaluated using multimodal imaging, including optical coherence tomography (OCT), fluorescein angiography, indocyanine green angiography, fundus autofluorescence, and ultrasound following treatment with half-dose and full-fluence PDT. Following half-dose PDT, all patients showed significant shrinkage of the hemangioma, functional improvement, and decrease of intra- and sub-retinal fluid. All patients remained stable after a single PDT treatment, with a follow-up of up to 60 months. No side effects were shown. This is the first report showing long term efficacy of half-dose PDT treatment in cases with CCH. The outcomes from this pilot study are comparable with results using full dose PDT protocols and it can be considered as a viable treatment option for CCH during the ongoing global verteporfin shortage.

Evaluation of a self-imaging SD-OCT system designed for remote home monitoring.

PURPOSE: To compare identification rates of retinal fluid of the Notal Vision Home Optical Coherence Tomography (OCT) device (NVHO) when used by people with age-related macular degeneration (AMD) to those captured by a commercial OCT. METHODS: Prospective, cross-sectional study where patients underwent commercial OCT imaging followed by self-imaging with either the NVHO 2.5 or the NVHO 3 in clinic setting. Outcomes included patients' ability to acquire analyzable OCT images with the NVHO and to compare those with commercial images. RESULTS: Successful images were acquired with the NVHO 2.5 in 469/531 eyes (88%) in 264/290 subjects (91%) with the mean (SD) age of 78.8 (8.8); 153 (58%) were female with median visual acuity (VA) of 20/40. In the NVHO 3 cohort, 69 eyes of 45 subjects (93%) completed the self-imaging. Higher rates of successful imaging were found in eyes with VA ≥ 20/320. Positive percent agreement/negative percent agreement for detecting the presence of subretinal and/or intraretinal fluid when reviewing for fluid in three repeated volume scans were 97%/95%, respectively for the NVHO v3. CONCLUSION: Self-testing with the NVHO can produce high quality images suitable for fluid identification by human graders, suggesting the device may be able to complement standard-of-care clinical assessments and treatments.

Is There a Dose-Response Relationship? Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Treatment in Neovascular Age-Related Macular Degeneration.

PURPOSE: The aim of study was to explore the dose-response relationship of anti-vascular endothelial growth factor (VEGF) agents, with bevacizumab as 1st-line treatment, on the visual-acuity (VA) outcome during the first year of treatment in neovascular AMD (nAMD) patients in real-life conditions. METHODS: This was a retrospective, observational, single-center study at the Ophthalmology Division, Tel Aviv Medical Center. Inclusion criterion was naive AMD patients treated with anti-VEGF injections between the years 2017-2020. Electronic medical records were scanned using the MDClone software, and data from time of diagnosis, containing baseline VA, final VA, number of injections, and the injected agent, were gathered. Subjects were divided into three groups based on their baseline VA ("good," "middle," and "low"). RESULTS: A total of 672 patients were included. The cohort demonstrated a statistically nonsignificant correlation with a positive trend between the log transformation of the number of annual injections and the change in VA (p = 0.145). However, a significant correlation was established within the "low-VA" group (p = 0.015). The "good-" and "middle-VA" groups did not reach statistical significance. Baseline VA was the single significant predictor for VA gain within patients with baseline VA of 6/12 or less. CONCLUSIONS: A dose-response relationship between anti-VEGF injections and the VA outcome was found only for patients with low baseline VA. Individual patient characteristics might need to be taken into account to customize treatment regimen and improve visual outcome.

IMPACT OF COVID-19 PANDEMIC LOCKDOWNS ON VISUAL ACUITY OF PATIENTS WITH NEOVASCULAR AMD: A Large Cohort.

PURPOSE: Evaluating the impact of delayed care, secondary to coronavirus disease 2019 (COVID-19) pandemic lockdowns, on visual acuity in previously treated neovascular age-related macular degeneration (nAMD) patients. METHODS: This was a multicenter, retrospective, study of patients with nAMD previously treated with anti-VEGF injections who were followed up during 2019 (pre-COVID-19) and compared with patients with nAMD during 2020 (COVID-19). RESULTS: A total of 1,192 patients with nAMD with a mean age of 81.5 years met the inclusion criteria. Of these, 850 patients were assessed in 2019 (pre-COVID-19) and 630 patients were assessed in 2020 (COVID-19). Three hundred eight patients were assessed through both 2019 and 2020 and thus were included in both cohorts. There was no significant difference between 2020 and 2019 in baseline and change in best-corrected visual acuity (BCVA; P = 0.342 and P = 0.911, respectively). The mean number of anti-VEGF injections was significantly lower (5.55 vs. 6.13, P < 0.01), with constant lower ratio of injections per patient in the COVID-19 period. Baseline BCVA (0.859, P < 0.01), number of injections (-0.006, P = 0.01), and age (0.003, P < 0.01) were predictors of final BCVA. CONCLUSION: In patients with nAMD, delayed care secondary to COVID-19 pandemic lockdowns has no statistically significant impact on BCVA. Best-corrected visual acuity, older age, and lower number of yearly anti-VEGF injections are predictors for decrease BCVA.

Additive Value of a Face-to-Face Visit to Virtual Remote Decision in Patients with Neovascular Age-Related Macular Degeneration.

INTRODUCTION: The increasing high prevalence of neovascular age-related macular degeneration (nvAMD) in the aging population combined with the need for frequent monitoring and treatment for many years, especially in the COVID-19 era, raises the need to establish an effective, reliable, and safe follow-up and treatment model. This study evaluates the difference in treatment decisions comparing between the gold standard face-to-face clinical examination and virtual evaluation approach based only on visual acuity (VA) and optical coherence tomography (OCT) scans without clinical fundoscopic examination in nvAMD patients. METHODS: A single-center retrospective cohort study was conducted that compared an original "face-to-face" visit treatment decision regarding the need for anti-vascular endothelial growth factor drug, interval, and treatment regimen based on routine VA, spectral domain OCT imaging, and dilated fundus examination to two "virtual" treatment decisions based on evaluation of OCT scans and previous medical records before and after revealing VA data on the same nvAMD patients eyes. RESULTS: About 169 eyes of 114 patients were included in the study. Forty-nine patients (43%) suffered from bilateral nvAMD and had both eyes included in the study. Agreement between the "face-to-face visit treatment decision" and "virtual treatment decision" was noted in 74.6% and 71.6% eyes before and after revealing the patient's VA in the study visit, respectively. CONCLUSIONS: Virtual evaluation results in similar treatment decisions for nvAMD patients compared to standard face-to-face clinical examination.

ACQUIRED VITELLIFORM LESIONS: A Novel Finding in Eyes with Peripapillary Pachychoroid Syndrome.

PURPOSE: To describe a novel finding of acquired vitelliform lesions in eyes with peripapillary pachychoroid syndrome. METHODS: A retrospective, multicenter, observational case series including seven patients with peripapillary pachychoroid syndrome and concomitant acquired vitelliform lesions. Medical records and multimodal imaging findings were comprehensively reviewed. RESULTS: Six of seven patients were men, with a mean age of 72.6 years. Mean baseline best-corrected visual acuity was 0.11 ± 0.07 (Snellen equivalent 20/25), and all patients presented with baseline best-corrected visual acuity of 20/30 or better. Mean follow-up time was 24.4 months (range 1-54 months). At last follow-up, best-corrected visual acuity was stable in 13/14 eyes, and deteriorated in one eye because of subfoveal atrophy.Fundus examination revealed peripapillary retinal pigment epithelium alterations and pigment migration in all eyes. Fundus autofluorescence showed mottled hyperautofluorescence and hypoautofluorescence in the peripapillary region, and hypoautofluorescent lesions corresponding to the pigmentary changes. Optical coherence tomography showed nasal choroidal thickening and pachyvessels with overlying retinal pigment epithelium irregularity. All eyes presented with peripapillary intraretinal fluid. Subretinal fluid was present in five eyes of three patients. Acquired vitelliform lesions were present in 11 eyes. CONCLUSION: The novel association between peripapillary pachychoroid syndrome and acquired vitelliform lesions is characterized by the classic findings of both entities, and visual prognosis is accordingly good.

Evaluation of a Telemedicine Model for Following Keratoconus Patients in the Era of COVID-19 Pandemic.

Purpose: To evaluate the diagnostic accuracy and reliability of a telemedicine approach for detecting keratoconus patients' progression in the era of coronavirus disease 2019 (COVID-19) pandemic. Materials and Methods: A retrospective study, comparing the office and telemedicine evaluations in determining whether keratoconus patients were at risk of progression and indicated for further treatment of corneal crosslinking, was conducted. The clinic examination included best spectacle corrected visual acuity measurement and manifest refraction, full ophthalmic examination, and corneal topography, which provided with the gold-standard diagnosis. The remote assessment included two decisions of keratoconus progression or stability: the first evaluation after revealing patient demographics and topography images, and the second with the manifest refraction and clinical findings as documented in the outpatient clinic visit. Results: Two-hundred and four eyes of 102 keratoconus patients were included. There was an agreement of assessment between the in-person and the remote diagnostic decisions in 192 (94%) of the eyes. Among the remaining 12 eyes, a false-positive diagnosis was made in 8 (3.9%) eyes, whereas a false-negative diagnosis was made in 4 (1.9%) eyes. The remote assessment showed a sensitivity and specificity of 69% and 96%, respectively. In no case was remote diagnostic decision 2 different from remote decision 1. Conclusions: The telemedicine model yielded high specificity, but low sensitivity values, therefore, not suitable as an alternative for keratoconus patient follow-up (Clinical trial number TLV-0363-20).

A 12-month prospective study to evaluate the efficacy of using the treat-and-extend regimen with intravitreal aflibercept as a Second-Line Treatment for Diabetic Macular Oedema (the TADI Study).

PURPOSE: To evaluate the efficacy of intravitreal aflibercept as a second-line therapy in eyes with persistent diabetic macular oedema (DMO) despite receiving initial bevacizumab treatment. METHODS: A prospective multicentre study was conducted in nine academic clinics in Israel. Starting from the first follow-up visit, a treat-and-extend regimen was applied in which the treatment intervals were extended by 2 weeks based on macular thickness using SD-OCT. The primary outcome was central subfield thickness (CST) at week 52. RESULTS: Forty-four patients (n = 48 eyes) were recruited to the study, and 43 eyes completed 52 weeks of follow-up. Patients received a mean (±SD) of 7.9 ± 3.5 bevacizumab injections before enrolment. The mean (±SD) CST under aflibercept therapy decreased from 468 ± 131 µm at baseline to 303 ± 67 µm at 52 weeks (p = 0.002), and best corrected visual acuity improved from 64 ± 15 ETDRS letters at baseline to 75 ± 8 letters at week 52 (p = 0.001). Twenty (46%) eyes met the treat-and-extend criteria and received a mean (±SD) of 10.9 ± 2 aflibercept injections. CONCLUSIONS: Eyes with persistent DMO following initial bevacizumab therapy had a marked reduction in macular thickness and improved visual acuity following 1 year of treatment with intravitreal aflibercept. Less than half of the patients met eligibility criteria for extension of the treatment interval; for these patients, the treat-and-extend regimen resulted in a maximum treatment interval of 10 weeks during the first year.

Prospective, Longitudinal Pilot Study: Daily Self-Imaging with Patient-Operated Home OCT in Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate longitudinally the performance of the Notal Vision Home OCT (NVHO), comprising a spectral-domain OCT device for patient self-imaging at home, telemedicine infrastructure for automated data upload, and deep learning algorithm for automated OCT evaluation. The aims were to study the system's performance in daily image acquisition and automated analysis and to characterize the dynamics of retinal fluid exudation in neovascular age-related macular degeneration (nAMD). Design: Pilot prospective, observational longitudinal study. Participants: Four individuals (mean age, 73.8 years) with nAMD (one or both eyes) undergoing anti-vascular endothelial growth factor therapy in routine clinical practice. Methods: The participants performed daily self-imaging at home with the NVHO for 1 month. The macular cube scans were uploaded automatically to the Notal Health Cloud. They underwent evaluation separately by the Notal OCT Analyzer (NOA) and human expert graders for fluid presence, segmentation, and volume. Main Outcome Measures: Daily self-imaging completion, image quality, acquisition time, agreement between automated and human grading of retinal fluid, and temporal dynamics of fluid volume. Results: Of 240 self-imaging attempts initiated, the number successfully completed was 211 (87.9%). Of these, 97.6% had satisfactory quality. For fluid presence, the NOA agreed with human grading in 94.7% of cases. From a subset of 24 scans with fluid, for agreement between NOA and human fluid volume measurements, the correlation coefficient was 0.996 and mean absolute difference was 1.5 nl (vs. 0.995 and 1.2 nl, respectively, for interhuman agreement). Graphic plots of fluid volume revealed wide variation in the dynamics of fluid exudation and treatment response. Conclusions: The participants could perform daily self-imaging at home and generate macular cube scans of satisfactory quality. Automated quantitative OCT analysis achieved high agreement with human grading. Daily self-imaging with automated OCT analysis permitted detailed characterization of the dynamics of fluid exudation and revealed wide variation between eyes. Metrics describing these dynamics may become important disease biomarkers. Home OCT telemedicine systems represent an alternative paradigm of disease monitoring; they may allow highly personalized retreatment decisions, with fewer unnecessary injections and clinic visits.

Vestibular function assessment of Susac syndrome patients by the video head impulse test and cervical vestibular-evoked myogenic potentials.

BACKGROUND: Susac syndrome (retino-cochleo-cerebral vasculopathy, SuS) is an autoimmune endotheliopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss. In contrast to data regarding auditory function, data measuring vestibular function is sparse and the cervical vestibular-evoked myogenic potentials (cVEMPs). OBJECTIVE: To determine whether the video head impulse test (vHIT) can serve as a confirmatory assessment of vestibulocochlear dysfunction in cases of suspected SuS. METHODS: Seven patients diagnosed with SuS underwent pure tone audiometry, a word recognition test, cVEMPs and the vHIT. RESULTS: Five patients were diagnosed with definite SuS, and two with probable SuS. Two patients were asymptomatic for hearing loss or tinnitus, and no sensorineural hearing loss was detected by audiograms. Four patients complained of tinnitus, and three patients reported experiencing vertigo. Three patients had abnormal cVEMPs results. All seven patients' vHIT results were normal, except for patient #2, who was one of the three who complained of vertigo. The calculated gain of her left anterior semicircular canal was 0.5, without saccades. CONCLUSIONS: This is the first study to describe the results of the vHIT and cVEMPs among a group of patients with SuS. The results suggest that the vHIT should not be the only exam used to assess the function of the vestibular system of SuS patients.

Vestibular function assessment of Susac syndrome patients by the video head impulse test and cervical vestibular-evoked myogenic potentials.

BACKGROUND: Susac syndrome (retino-cochleo-cerebral vasculopathy, SuS) is an autoimmune endotheliopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss. In contrast to data regarding auditory function, data measuring vestibular function is sparse. OBJECTIVE: To determine whether the video head impulse test (vHIT) can serve as a confirmatory assessment of vestibulocochlear dysfunction in cases of suspected SuS. METHODS: Seven patients diagnosed with SuS underwent pure tone audiometry, a word recognition test, cervical vestibular-evoked myogenic potentials (cVEMPs), and the v-HIT. RESULTS: Five patients were diagnosed with definite SuS, and two with probable SuS. Two patients were asymptomatic for hearing loss or tinnitus, and no sensorineural hearing loss was detected by audiograms. Four patients complained of tinnitus, and three patients reported experiencing vertigo. Three patients had abnormal cVEMPs results. All seven patients' vHIT results were normal, except for patient #2, who was one of the three who complained of vertigo. The calculated gain of her left anterior semicircular canal was 0.5, without saccades. CONCLUSIONS: This is the first study to describe the results of the vHIT and cVEMPs among a group of patients with SuS. The results suggest that the vHIT should not be the only exam used to assess the function of the vestibular system of SuS patients.

A Collaborative Retrospective Study on the Efficacy and Safety of Intravitreal Dexamethasone Implant (Ozurdex) in Patients with Diabetic Macular Edema: The European DME Registry Study.

PURPOSE: To evaluate the efficacy, effect profile, and safety of dexamethasone implant on diabetic macular edema (DME) in a real-life setting, further comparing results by DME duration, previous treatment status, and diabetic control. DESIGN: A multicenter, retrospective cohort of 340 DME eyes of 287 patients from 25 clinical sites from 8 countries. METHODS: Data were analyzed in 2 perspectives: per injection, in which all measurements were grouped and baseline was defined as the day of injection, and thus the pharmacodynamics of single injections could be assessed; and injection series, defined as 2 or more injections with 3 to 6 months between injections analyzing the outcome 3 to 6 months after the last injection. MAIN OUTCOME MEASURES: Primary outcome was improvement of 15 or more letters in best-corrected visual acuity (BCVA) from baseline. Secondary outcomes included improvement of 10 letters or more in BCVA, change in central macular thickness (CMT), and time to maximum improvement and safety. RESULTS: Overall, 762 injections were administered to 340 eyes of 287 patients. Injection series analysis included 171 series in 171 eyes of 150 patients, for a total of 444 injections, with a mean follow-up of 1.7±0.8 years. Of the 762 injections analyzed per injection, 22.7% achieved a 15-letter or more improvement, and 37.8% achieved a 10-letter or more improvement. Mean time to peak improvement was 81.9±39.7 days. Mean maximum change in CMT was -174±171 µm. Overall, 7.6% lost 15 or more letters. More eyes with early DME gained 10 or more letters and fewer eyes lost 10 or more letters compared with eyes with late DME (47.4% vs. 33.9% [P = 0.001] and 8.2% vs. 13.5% [P = 0.029], respectively). Patients with controlled diabetes showed greater CMT reduction (P = 0.0002). A higher percentage of treatment-naive patients gained 10 or 15 letter or more in BCVA (P = 0.001 and P = 0.006, respectively). Intraocular pressure elevation of more than 25 mmHg was found following 7.9% of injections; no endophthalmitis was reported. CONCLUSIONS: Dexamethasone implant is an effective and safe treatment for DME. Peak improvement was achieved 3 months after injection and dissipated thereafter. Clinicians and providers may consider shortening treatment intervals.

DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study.

PURPOSE: To investigate efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment. METHODS: This multicenter international retrospective study assessed best-corrected visual acuity and central subfield thickness (CST) of naive and refractory eyes to anti-vascular endothelial growth factor injections treated with dexamethasone implants. Safety data (intraocular pressure rise and cataract surgery) were recorded. RESULTS: A total of 130 eyes from 125 patients were included. Baseline best-corrected visual acuity and CST were similar for naive (n = 71) and refractory eyes (n = 59). Both groups improved significantly in vision after 24 months (P < 0.001). However, naive eyes gained statistically significantly more vision than refractory eyes (+11.3 ± 10.0 vs. 7.3 ± 2.7 letters, P = 0.01) and were more likely to gain ≥10 letters (OR 3.31, 95% CI 1.19-9.24, P = 0.02). At 6, 12, and 24 months, CST was significantly decreased compared with baseline in both naive and refractory eyes; however, CST was higher in refractory eyes than in naive eyes (CST 279 ± 61 vs. 313 ± 125 µm, P = 0.10). CONCLUSION: Over a follow-up of 24 months, vision improved in diabetic macular edema eyes after treatment with dexamethasone implants, both in eyes that were treatment naive and eyes refractory to anti-vascular endothelial growth factor treatment; however, improvement was greater in naive eyes.

ACCURACY AND PRECISION OF INTRAVITREAL INJECTIONS OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS IN REAL LIFE: What Is Actually in the Syringe?

PURPOSE: To evaluate the accuracy and precision of anti-vascular endothelial growth factor volume delivery by intravitreal injections in the clinical setup. METHODS: Volume output was measured in 669 intravitreal injections administered to patients, calculated from the difference in syringe weight before and after expelling the drug. Three groups were included: prefilled bevacizumab 1.0 mL syringe (Group 1, n = 432), pre-filled ranibizumab in a small-volume syringe with low dead-space plunger design (Group 2, n = 125), and aflibercept drawn and injected using a 1.0-mL syringe (Group 3, n = 112). Accuracy was analyzed by mean absolute percentage error, and precision by coefficient of variation. RESULTS: Volume outputs in all 3 groups were significantly different from the target of 50 µL (P < 0.0001 for all), and mean absolute percentage error values were 12.25% ± 5.92% in Group 1, 13.60% ± 8.75% in Group 2, and 24.69% ± 14.84% in Group 3. No difference was found between groups 1 and 2, but both were significantly more accurate than Group 3 (P < 0.0001 for both). CONCLUSION: The current practices used for intravitreal injections are highly variable, with overdelivery of the anti-vascular endothelial growth factor drugs measured in most cases, but underdelivery in 16.3% of injections. Use of a prefilled syringe was associated with improved accuracy, and low dead-space plunger design may improve precision.

Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel (DERBI study).

PURPOSE:: To evaluate the outcome of second-line intravitreal ranibizumab treatment in eyes with diabetic macular edema having persistent edema following initial therapy with intravitreal bevacizumab. METHODS:: Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel was a retrospective, multi-center study. Consecutive eyes with persistent diabetic macular edema following at least three previous intravitreal bevacizumab injections prior to intravitreal ranibizumab, at least three-monthly intravitreal ranibizumab injections and at least 12 months of follow-up were included. Data collected included demographics, ocular findings, diabetes control, details of intravitreal bevacizumab and ranibizumab injections, and visual and anatomical measurements before and after intravitreal ranibizumab treatment. RESULTS:: In total, 202 eyes of 162 patients treated at 11 medical centers across Israel were included. Patients received a mean (±standard deviation) of 8.8 ± 4.9 intravitreal bevacizumab injections prior to the switch to intravitreal ranibizumab. A mean of 7.0 ± 2.7 intravitreal ranibizumab injections were given during the 12 months following the switch to intravitreal ranibizumab. The median central subfield retinal thickness (±interquartile range) by spectral-domain optical coherence tomography decreased from 436 ± 162 µm at baseline to 319 ± 113 µm at month 12 (p < 0.001). Median logMAR visual acuity (±interquartile range) improved from 0.40 ± 0.48 at baseline to 0.38 ± 0.40 at month 12 (p = 0.001). Linear regression suggested that higher number of intravitreal ranibizumab injections and higher pre-switch central subfield retinal thickness were associated with favorable visual outcome. Higher number of intravitreal bevacizumab injections and the presence of intraretinal fluid before the switch lessened the odds of favorable outcome. CONCLUSION:: Switching from bevacizumab to ranibizumab in persistent diabetic macular edema was associated with anatomical improvement in the majority of eyes and ⩾2 lines of vision improvement in 22% of eyes.