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.

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.

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.

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.

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.

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.

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.

Disorganization of Retinal Inner Layers as a Biomarker for Idiopathic Epiretinal Membrane After Macular Surgery-The DREAM Study.

PURPOSE: Epiretinal membrane (ERM) can cause distortion and disorganization of all inner retinal layers. The purpose of our study was to evaluate the extent of disorganization of the retinal inner layers (DRIL) and to investigate its predictive value for visual outcome in cases of idiopathic ERM that were treated by pars plana vitrectomy (PPV) and ERM peeling. DESIGN: Multicenter international retrospective case series. METHODS: In 90 eyes from 90 patients with idiopathic ERM treated by PPV and membrane peeling with 12-month follow-up, optical coherence tomography (OCT) scans previous to surgery were evaluated for presence and severity of DRIL, central foveal subfield thickness (CST), maximal retinal thickness (MRT), presence of intraretinal cystoid changes and subretinal fluid, and integrity of the inner/outer segment layer and of the interdigitation zone. Best-corrected visual acuity (BCVA), CST, and MRT were recorded at baseline and at 3, 6, and 12 months after surgery. Correlations between baseline OCT measures (DRIL) and functional and visual outcome were analyzed. Main outcome measures are presence and severity of DRIL at baseline; anatomic and functional outcomes after 3, 6, and 12 months; and the correlation between DRIL and baseline characteristics and outcome measures. RESULTS: Patients without and with mild DRIL had a significantly better baseline BCVA compared with patients with severe DRIL (0.61 ± 0.13, 0.56 ± 0.23, 0.73 ± 0.20 [logMAR], respectively). BCVA, CST, and MRT at baseline were statistically significantly correlated with DRIL severity (P = .003, P < .001, and P < .001, respectively). DRIL status before surgery showed a statistically significant interaction with change in BCVA, CST, and MRT over 12 months (P < .001 for all). Patients without and with mild DRIL gained a mean of 3 lines of vision after 12 months, in contrast to 1 line in patients with severe DRIL. CONCLUSIONS: DRIL grading correlates with functional and anatomic measures in patients with idiopathic ERM and could serve as a biomarker to predict outcome after surgery. Patients with severe DRIL have limited benefits from surgery. This should be considered in the decision process whether to perform ERM peeling in this patient group.

Prevalence of choroidal nevus and retinal pigment epithelial alterations in vitiligo patients.

PURPOSE: To investigate ocular manifestations in patients with vitiligo by multimodal imaging, including optical coherence tomography (OCT), color fundus photography, and fundus autofluorescence (FAF). METHODS: In this prospective, observational clinical study, vitiligo patients underwent ophthalmologic and dermatologic clinical assessment and imaging by spectral-domain OCT, FAF, and color fundus imaging. Ocular echography was performed as indicated. Statistical analysis was performed using paired T test and Pearson correlation. RESULTS: A total of 61 eyes of 31 vitiligo patients were examined. Ocular findings consisted of choroidal nevi (n = 10, 32%), of which four (40%) were bilateral; two patients (6.5%) had a prominent choroidal pattern, two (6.5%) had hypopigmentary retinal pigment epithelium (RPE) lesions, and one (3.2%) had peripapillary atrophy of the RPE. Choroidal nevi were demonstrated only in eyes of patients with generalized vitiligo and were more common with upper body involvement (p = 0.02) and more prevalent in women (p = 0.02). Hypopigmentary lesions were detected in two patients and demonstrated on OCT as RPE atrophy and as photoreceptor/RPE changes. CONCLUSIONS: In this case series, vitiligo patients had a higher rate of choroidal nevi than previously reported. The hypopigmentary vitiliginous fundus lesions were depicted on OCT as photoreceptor and RPE atrophy. These findings may suggest the advisability of regular ocular monitoring for vitiligo patients.

CHANGES IN CHOROIDAL THICKNESS IN CLINICALLY SIGNIFICANT PSEUDOPHAKIC CYSTOID MACULAR EDEMA.

PURPOSE: To investigate choroidal thickness in eyes with clinically significant pseudophakic cystoid macular edema (PCME) during the acute phase and following resolution of the edema, using enhanced depth imaging spectral domain optical coherence tomography (EDI-OCT). METHODS: This is a retrospective, observational clinical study. Patients' records were reviewed for cases of clinically significant PCME after uneventful phacoemulsification surgery. Choroidal thickness was measured at time of PCME diagnosis in both eyes and after CME resolution in the affected eye using enhanced depth imaging spectral domain optical coherence tomography (Spectralis; Heidelberg Engineering). Measurements were taken subfoveal and 1.5 mm nasal, temporal, inferior, and superior from the center of the fovea. Statistical analysis was performed using paired t-test and Pearson correlation. RESULTS: Mean subfoveal choroidal thickness in 34 eyes with PCME measured 258 ± 83 µm at baseline and decreased to 215 ± 79 µm after CME resolution (P < 0.001). Mean subfoveal choroidal thickness measured at baseline in fellow eyes was significantly lower (194 ± 77 µm) compared to acute PCME (P < 0.001) and after CME resolution (P = 0.011). CONCLUSION: Choroidal thickness is increased in eyes with PCME and decreases following edema resolution. These findings may strengthen the hypothesis of an inflammatory pathogenesis in PCME.

Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative Stress.

Oxidative stress leads to the degeneration of retinal pigment epithelial (RPE) and photoreceptor cells. We evaluated the potential of adipose-derived mesenchymal stem cells (ASCs) as a therapeutic tool by studying the migration capacity of ASCs in vitro and their protective effect against RPE cell death under oxidative stress in vitro and in vivo. ASCs exhibited enhanced migration when exposed to conditioned medium of oxidative stressed RPE cells obtained by hydrogen peroxide. Migration-related axis SDF-1/CXCR4 was studied, and upregulation of SDF-1 in stressed RPE and of CXCR4 in ASCs was detected. Moreover, ASCs' conditioned medium prevented H2O2-induced cell death of RPE cells. Early passage ASCs had high expression level of HGF, low VEGF levels, and unmodulated IL-1ß levels, compared to late passage ASCs. Thus, early passage ASCs show the potential to migrate towards damaged RPE cells and protect them in a paracrine manner from cell death induced by oxidative stress. In vivo, mice received systemic injection of NaIO3, and 72 h later, ASCs were transplanted in the subretinal space. Seven days after ASC transplantation, the eyes were enucleated fixed and frozen for immunohistochemical analysis. Under such conditions, ASC-treated mice showed preservation of nuclear layers in the outer nuclear layer and stronger staining of RPE and photoreceptor layer, compared to PBS-treated mice. Taken together, our results indicate that ASCs are able to home in on damaged RPE cells and protect against damage to the RPE and PR layers caused by oxidative stress. These data imply the potential that ASCs have in regenerating RPE under oxidative stress, providing the basis for a therapeutic approach to retinal degeneration diseases related to oxidative stress that could help save the eyesight of millions of people worldwide.

Association between Cataract and Keratinocytic Skin Cancers or Melanoma: Speculating on the Common Role of Sun and Ultraviolet Radiation Exposures.

PURPOSE: Cataract and sun-related skin conditions are proxies to lifetime UV exposure. We examined the association between them using real-world data from an unselected Israeli population. METHODS: Computerized data was obtained from an Israeli health maintenance organization regarding cases of sun-related skin pathologies and cataract diagnosed between 2006 and 2011 in 686,260 members aged 40 or above. RESULTS: Sun-related skin disorders were found in 9.3% of the study population, more commonly among the elderly, and those who reside in areas of higher socioeconomic status. Cataract was diagnosed in 13.1% of the study population, with highest prevalence (47%) among squamous cell carcinoma patients, who were the oldest group. Multivariable analysis adjusting for age, sex, residential district, birth region, smoking, and chronic comorbidities showed no statistically significant association between melanoma and cataract (OR = 1.06; 95% CI: 0.91-1.22). Basal cell carcinoma, squamous cell carcinomas, and actinic keratosis were associated with increased likelihood of prevalent cataract with adjusted odds ratios (95% CI) of 1.14 (1.08-1.20), 1.11 (1.01-1.19), and 1.16 (1.13-1.19), respectively. When stratified by gender, the association between actinic keratosis and cataract was stronger in women than in men, particularly in patients under 65 years. CONCLUSIONS: The association between the prevalence of skin cancers and the prevalence of cataract enhances the conclusion that cataract is related to UVR exposure.

Bevacizumab treatment of macular edema in CRVO and BRVO: long-term follow-up. (BERVOLT study: Bevacizumab for RVO long-term follow-up).

PURPOSE: To assess the efficacy and safety of intraocular injections of bevacizumab in patients with macular edema (ME) following branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). METHODS: Retrospective, non-comparative case series. Patients ≥18 years of age with ME secondary to BRVO or CRVO who received a minimum of one intravitreal injection of bevacizumab with a follow-up >3 months were included. Primary endpoints were mean change in best corrected visual acuity (BCVA) from baseline to 12 and 24 months, and mean change in central macular thickness (CMT) after 3 injections. Secondary endpoints were mean change in BCVA and CMT from baseline to end of follow-up, number of injections, and ocular adverse events. RESULTS: Eighty-seven eyes with BRVO and 65 eyes with CRVO were included. Mean follow-up time was 24.4 and 26.1 months in the BRVO and CRVO groups, respectively. The mean change in BCVA was 0.25 LogMAR in the BRVO group and -0.118 LogMAR in the CRVO group. CONCLUSION: Visual acuity outcomes in the CRVO group were poorer, especially in patients with low baseline BCVA.

Scheduled versus Pro Re Nata Dosing in the VIEW Trials.

PURPOSE: To analyze visual acuity (VA) outcomes before and after preplanned treatment regimen change in the VIEW studies at week 52 (W52). DESIGN: Multiple post hoc analyses for retrospectively defined subgroups in 2 multicenter, multinational, double-masked trials. PARTICIPANTS: Two thousand four hundred fifty-seven neovascular age-related macular degeneration (AMD) patients. METHODS: Patients were randomized to treatment with 0.5 mg ranibizumab given monthly, a 0.5-mg or 2-mg intravitreal aflibercept injection given monthly, or 2 mg intravitreal aflibercept given every other month, after 3 initial monthly doses, up to W52. From W52 through W96, patients received their original dosing assignment using a capped pro re nata (PRN) regimen, with defined retreatment criteria based on VA and morphologic signs of disease activity and mandatory dosing at least every 12 weeks. MAIN OUTCOME MEASURES: Best-corrected VA (BCVA) and optical coherence tomography assessments were mandatory at all visits from baseline to W96. Outcomes were changes in BCVA and central retinal thickness. Outcomes were evaluated in all patients who completed 2 years of the VIEW studies using the last observation carried forward method for missing data at interim visits. RESULTS: After W52, approximately 20% of patients lost 5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more across all treatment arms with PRN treatment. Patients who met the retreatment criterion of loss of 5 ETDRS letters or more in the first quarter of the PRN dosing phase did not recover; mean final VA loss across the 4 study arms was -4.4 to -5.8 letters. Outcomes of these patients up to W52 were indistinguishable from those of the overall population. There were no differences between groups in serious ocular adverse events or Anti-Platelet Trialists' Collaboration arterial thromboembolic events through W96. CONCLUSIONS: These analyses suggest that there are subgroups of patients for whom VA outcomes in the second year of the VIEW studies were less stable than in the first year and for whom W52 seems to be an important inflection point. Although alternate reasons specific to the nature of the underlying AMD cannot be fully excluded, the switch in treatment regimen at W52 is a plausible explanation.

SWITCHING TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FROM BEVACIZUMAB TO RANIBIZUMAB: Who is Likely to Benefit From the Switch?

PURPOSE: To evaluate the safety and efficacy of switching from bevacizumab to ranibizumab in patients with neovascular age-related macular degeneration. METHODS: Retrospective study of patients with neovascular age-related macular degeneration initially treated with bevacizumab and switched to ranibizumab. Visual acuity and central retinal thickness (CRT) were retrieved at four time points: before the last three bevacizumab injections, at the switch, after the first three ranibizumab injections, and at the end of follow-up. RESULTS: One hundred and fourteen eyes of 110 patients were included. Switching from bevacizumab to ranibizumab did not achieve a significant change in visual acuity, and a significant reduction in CRT was achieved after the first three injections but was not maintained by the end of follow-up. Eyes that lost ≥0.1 logMAR before the switch were more likely to improve in visual acuity (P = 0.013), and eyes with ≥10% increase in CRT before the switch were more likely to improve anatomically (P = 0.0003). In 47.3% of the eyes, the CRT was reduced by ≥10% after the first 3 ranibizumab injections, and the reduction was maintained with additional injections. CONCLUSION: Switching to ranibizumab should be considered in patients with visual acuity decrease or CRT increase, despite monthly bevacizumab injections. The response should be evaluated after the first three injections to guide future treatment.

Dexamethasone Intravitreal Implant as Adjunctive Therapy to Ranibizumab in Neovascular Age-Related Macular Degeneration: A Multicenter Randomized Controlled Trial.

PURPOSE: To evaluate the efficacy and safety of dexamethasone intravitreal implant 0.7 mg (DEX) as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration (nvAMD). PROCEDURES: This was a 6-month, single-masked, multicenter study. Patients were randomized to DEX implant (n = 123) or sham procedure (n = 120) and received 2 protocol-mandated intravitreal ranibizumab injections. The main outcome measure was injection-free interval to first as-needed ranibizumab injection. RESULTS: DEX increased the injection-free interval versus sham (50th percentile, 34 vs. 29 days; 75th percentile, 85 vs. 56 days; p = 0.016). 8.3% of DEX versus 2.5% of sham-treated patients did not require rescue ranibizumab (p = 0.048). Visual acuity and retinal thickness outcomes were similar in DEX and sham-treated patients. Only reports of conjunctival hemorrhage (18.2 vs. 8.5%) and intraocular pressure elevation (13.2 vs. 4.2%) were significantly different in the DEX versus the sham treatment groups. CONCLUSION: DEX reduced the need for adjunctive ranibizumab treatment and showed acceptable tolerability in nvAMD patients.