Initial response and 12-month outcomes after commencing dexamethasone or vascular endothelial growth factor inhibitors for retinal vein occlusion in the FRB registry.

To compare baseline characteristics, initial response and 12-month efficacy and safety outcomes in eyes with branch and central retinal vein occlusion (BRVO and CRVO) treated with dexamethasone implants (DEX) or anti-vascular endothelial growth factor (anti-VEGF) we performed a multi-centre, retrospective and observational study using Fight Retinal Blindness! Registry. Of 725 eligible eyes, 10% received DEX initially with very frequent adjunctive anti-VEGF (BRVO-DEX 49%, CRVO-DEX 60%). The primary outcome of mean adjusted change in VA at 12 months with DEX and anti-VEGF initiated groups were not statistically significantly different (BRVO: DEX + 6.7, anti-VEGF + 10.6 letters; CRVO: DEX + 2.8, anti-VEGF + 6.8 letters). DEX initiated eyes had fewer injections and visits than anti-VEGF initiated eyes. The BRVO-DEX eyes had greater initial mean changes in VA and central subfield thickness (CST) and achieved inactivity sooner than BRVO-anti-VEGF eyes. The mean CST after the first three months was above 350 µm in all but the BRVO-anti-VEGF group, suggesting undertreatment. In routine care DEX is uncommonly used when available as initial treatment of BRVO and CRVO requiring supplemental anti-VEGF within the first year. The 12-month outcomes were similar, but DEX initiated eyes had fewer injections and visits but more episodes of raised IOP Vs those starting anti-VEGF.

Artificial intelligence-based fluid quantification and associated visual outcomes in a real-world, multicentre neovascular age-related macular degeneration national database.

AIM: To explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration (nAMD) treated eyes. METHODS: Demographics, visual acuity (VA), drug and number of injections data were collected using a validated web-based tool. Fluid compartment quantifications including intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) in the fovea (1 mm), parafovea (3 mm) and perifovea (6 mm) were measured in nanoliters (nL) using a validated AI-tool. RESULTS: 452 naïve nAMD eyes presented a mean VA gain of +5.5 letters with a median of 7 injections over 12 months. Baseline foveal IRF associated poorer baseline (44.7 vs 63.4 letters) and final VA (52.1 vs 69.1), SRF better final VA (67.1 vs 59.0) and greater VA gains (+7.1 vs +1.9), and PED poorer baseline (48.8 vs 57.3) and final VA (55.1 vs 64.1). Predicted VA gains were greater for foveal SRF (+6.2 vs +0.6), parafoveal SRF (+6.9 vs +1.3), perifoveal SRF (+6.2 vs -0.1) and parafoveal IRF (+7.4 vs +3.6, all p<0.05). Fluid dynamics analysis revealed the greatest relative volume reduction for foveal SRF (-16.4 nL, -86.8%), followed by IRF (-17.2 nL, -84.7%) and PED (-19.1 nL, -28.6%). Subgroup analysis showed greater reductions in eyes with higher number of injections. CONCLUSION: This real-world study describes an AI-based analysis of fluid dynamics and defines baseline OCT-based patient profiles that associate 12-month visual outcomes in a large cohort of treated naïve nAMD eyes nationwide.

Macular Neovascularization Type Influence on Anti-VEGF Intravitreal Therapy Outcomes in Age-Related Macular Degeneration.

PURPOSE: To evaluate the influence of macular neovascularization (MNV) lesion type on 12-month clinical outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF drugs nationwide. DESIGN: Multicenter national nAMD database observational study. SUBJECTS: One thousand six hundred six treatment-naive nAMD eyes (1330 patients) undergoing anti-VEGF therapy for 12 months nationwide. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, number of injections and visits were was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n = 711), type 2 (T2, n = 505), type 3 (T3, n = 315), and aneurysmal type 1 (A-T1, n = 75), according to the new proposed consensus classification. MAIN OUTCOME MEASURES: Mean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation. RESULTS: A total of 1606 treatment-naive nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (± standard deviation) baseline VA was significantly lower for T2 (49.4 ± 23.5 letters) compared with T1 (57.8 ± 20.8) and T3 (58.2 ± 19.4) (both P < 0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared with T3 (+3.1 letters, P < 0.05). Patients with T3 lesions had fewer active visits (24.9%) than those with other lesion types (T1, 30.5%; T2, 32.6%; A-T1, 27.5%; all P < 0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%), and T3 (47.6%) lesions. CONCLUSIONS: This study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change, and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support personalized clinical decision making for these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Creation of a neovascular age-related macular degeneration national database using a web-based platform: Fight Retinal Blindness Spain. Report 1: Visual outcomes.

BACKGROUND: To study the visual outcomes of neovascular AMD (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs at national level. METHODS: Multicenter national database of nAMD eyes treated with anti-VEGF intravitreal injections (ranibizumab, aflibercept, bevacizumab) in fixed bimonthly (FB) or treat-and-extend (TAE) regimens. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) ETDRS letters at baseline and subsequent visits, number of injections and visits data were collected using a validated web-based tool (Fight Retinal Blindness!). RESULTS: 1273 eyes (1014 patients) were included, 971 treatment naïve (TN) and 302 previously treated (PT). Baseline VA (mean ± SD) was 57.5 (±19.5) and 62.2 (±17) (p > 0.001), and 24 months final VA was 60.4 (±21.2) and 58.8 (±21.1) (p = 0.326), respectively. Mean VA change at 12/24 months was +4.2/+2.9 letters in TN eyes and +0.1/-3.4 letters in PT eyes (p < 0.001/p < 0.001). The percentage of ≥15 letters gainers/losers at 24 months was 24.8%/14.5% in TN, and 10.3%/15.7% in PT eyes. The median number of injections/visits at 12 months was 7/9 in TN and 6/8 in PT (p = 0.002/p < 0.001) and at 24 months was 11/16 in TN and 11/14 in PT (p = 0.329/p < 0.001). Study drugs included ranibizumab (39.5%), aflibercept (41.2%) and bevacizumab (19.3%). CONCLUSION: Independent, large-scale national audits are feasible if committed health care professionals are provided with efficient information technology systems to do them. The results described here represent an adequate measurement of the quality of care delivered nationwide and benchmark the clinical management of nAMD at a country level compared to other real-world international cohorts.

Prediction Error Stabilization and Long-Term Standard Results with a Monofocal Intraocular Lens.

The aim of this study was to assess the stability and differences between objective (O-Rx) and subjective (S-Rx) refraction for the assessment of the prediction error (PE). A secondary aim was to report the results of a monofocal intraocular lens (IOL). 100 subjects were included for whom S-Rx and O-Rx were obtained for all visits, and for visual performance, posterior capsular opacification incidence and Nd:YAG rates at 12 months. Either S-Rx and O-Rx showed a hyperopic shift from 1 to 6 months (p < 0.05) and stabilization after 6 months. S-Rx was related with the axial length (rho = -0.29, p = 0.007), obtaining a major tendency towards hyperopia in short eyes implanted with high-power IOLs. O-Rx showed a myopic shift in comparison to S-Rx (p < 0.05). This resulted in a decrease of the number of eyes in ±0.50 D and ±1.00 D from 79 to 67% and from 94 to 90%, respectively. The median (interquartile range) uncorrected and corrected visual acuities were 0.1 (0.29) and 0 (0.12) logMAR, respectively, and seven eyes required Nd:YAG capsulotomy at 12 months. Some caution should be taken in PE studies in which O-Rx is used or S-Rx is measured in a 1-month follow-up. Constant optimization should be conducted for this IOL after S-Rx stabilization.

Short-term effectiveness prognostic factors after dexamethasone intravitreal implant in macular edema due to retinal vein occlusion.

INTRODUCTION: The aim of this study was to describe functional and anatomical changes (best-corrected visual acuity [BCVA], central macular thickness [CMT], and central macular volume [CMV]) in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) treated with intravitreal dexamethasone implant (IDI) and identify its clinical predictors in a real-world setting. METHODS: Data from 111 patients who underwent IDI to treat RVO-associated ME were retrospectively reviewed. Demographic, preoperative, and postoperative variables were assessed using a logistic regression analysis to determine predictors of visual and anatomical improvement. RESULTS: Mean BCVA, CMT, and CMV improved from baseline after IDI (p < 0.001). The strongest predictors of different treatment outcomes were: a baseline BCVA ⩽60 ETDRS letters (OR = 50.600; p < 0.001) and first IDI injection (OR = 2.988; p < 0.001) for BCVA gain ⩾15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters; a baseline BCVA ⩽60 ETDRS letters (OR = 7.893; p = 0.002) and non-chronic ME (OR = 3.875; p = 0.019) for BCVA ⩾80 ETDRS letters achievement; a baseline CMT ⩾400 µm (OR = 49.083; p < 0.001) and a baseline CMV ⩾12 mm3 (OR = 4.235; p < 0.001) for CMT reduction ⩾50%; and a baseline CMT ⩾400 µm (OR = 11.471; p < 0.001) and a baseline CMV ⩾12 mm3 (OR = 10.284; p < 0.001) for CMV reduction ⩾15%. CONCLUSION: This study confirmed the effectiveness of IDI to treat ME secondary to RVO and identified new predictive factors for two visual (⩾15 ETDRS letters gain and BCVA ⩾80 ETDRS letters) and two anatomical outcomes (>50% CMT and >15% CMV reduction).

Three-Year Outcomes of Neovascular Age-Related Macular Degeneration in Eyes That Do Not Develop Macular Atrophy or Subretinal Fibrosis.

Purpose: To report the 36-month treatment outcomes of eyes with neovascular age-related macular degeneration (nAMD) receiving vascular endothelial growth factor (VEGF) inhibitors in daily practice who did not develop either subretinal fibrosis (SRFi) or macular atrophy (MA). Methods: This is a retrospective analysis of data from the Fight Retinal Blindness registry. Treatment-naïve eyes starting intravitreal injection of VEGF inhibitors for nAMD from January 1, 2010, to September 1, 2017, and did not have SRFI and MA at baseline were tracked. Results: We identified 2478 eligible eyes, of which 1712 eyes did not develop SRFi or MA, 291 developed extrafoveal SRFI or MA, and 475 developed subfoveal SRFi or MA over 36 months. The estimated visual acuity stabilized from 6 months to 36 months in eyes that did not develop SRFI or MA with a mean (95% confidence interval [CI]) change in VA of -1 (-2, 0) letters, whereas eyes that developed extrafoveal (-3 [-5, -2] letters) or subfoveal (-10 [-11, -8] letters) SRFi or MA declined in vision in the same period. Eyes with no or extrafoveal SRFi or MA over 36 months were more likely to maintain their visual improvement from six months to 36 months (odds ratio [OR; 95% CI] = 2.3 [1.5, 3.3] for absence vs. subfoveal SRFi or MA, P ≤ 0.01 and OR = 2.0 [1.2, 3.4] for extrafoveal vs. subfoveal MA or SRFi, P = 0.01). Conclusions: Treatment-naïve nAMD eyes receiving VEGF inhibitors maintain their initial six-month visual improvement over three years if they do not develop SRFI or MA. Translational Relevance: The nAMD is still a major cause of blindness despite antiangiogenic treatments. We found that eyes that did not develop subretinal fibrosis or macular atrophy maintained their initial vision improvement for at least three years, suggesting that identifying treatments for these complications is the final barrier to achieving excellent outcomes in nAMD.

Global multi-site, prospective analysis of cataract surgery outcomes following ICHOM standards: the European CAT-Community.

PURPOSE: To evaluate in a large sample of patients from 10 different European centers the results of cataract surgery, characterizing the relationship between patient-reported outcomes (PROMs) and clinician-reported outcome measures (CROMs). METHODS: Prospective non-interventional multicenter observational descriptive study analyzing the clinical outcomes of a total of 3799 cases undergoing cataract surgery (mean age: 72.7 years). In all cases, the cataract surgery standard developed by the International Consortium for Health Outcomes Measurements (ICHOM) was used to register the clinical data. Three-month postoperative visual acuity and refraction data were considered CROMs, whereas Rasch-calibrated item 2 (RCCQ2) and total Catquest-9SF score (CQ) were considered PROMs. RESULTS: Postoperative corrected distance visual acuity (CDVA) was 0.3 logMAR or better in 88.7% (2505/2823) of eyes. Mean differences between preoperative and postoperative RCCQ2 and CQ scores were -3.09 and -2.39, respectively. Visual function improvement with surgery was reported by 91.5% (2163/2364) of patients. Statistically significant, although weak, correlations of postoperative CDVA with postoperative refraction, PROMs, and complications were found (0.133 ≤ r ≤0.289, p < 0.001). A predictive model (R2: 0.254) of postoperative CDVA considering 10 variables was obtained, including preoperative CDVA, different ocular comorbidities, age, gender and intraoperative complications. Likewise, another predictive model (R2: 0.148) of postoperative CQ considering a total of 14 variables was obtained, including additionally preoperative CQ, target refraction and previous surgeries. CONCLUSIONS: Cataract surgery provides an improved functional vision in most of patients although this improvement can be limited by ocular comorbidities and complications. The relationship between PROMs and CROMs is multifactorial and complex.

Recommendations for ophthalmologic practice during the easing of COVID-19 control measures.

In the context of the COVID-19 pandemic, this paper provides recommendations for medical eye care during the easing of control measures after lockdown. The guidelines presented are based on a literature review and consensus among all Spanish Ophthalmology Societies regarding protection measures recommended for the ophthalmologic care of patients with or without confirmed COVID-19 in outpatient, inpatient, emergency and surgery settings. We recommend that all measures be adapted to the circumstances and availability of personal protective equipment at each centre and also highlight the need to periodically update recommendations as we may need to readopt more restrictive measures depending on the local epidemiology of the virus. These guidelines are designed to avoid the transmission of SARS-CoV-2 among both patients and healthcare staff as we gradually return to normal medical practice, to prevent postoperative complications and try to reduce possible deficiencies in the diagnosis, treatment and follow-up of the ophthalmic diseases. With this update (5th ) the Spanish Society of Ophthalmology is placed as one of the major ophthalmology societies providing periodic and systematized recommendations for ophthalmic care during the COVID-19 pandemic.

Safety and efficacy of bilateral simultaneous XEN implant surgery: a pilot study.

OBJECTIVE: To evaluate the efficacy and safety of the bilateral simultaneous XEN (BISIXEN) surgery in open-angle glaucoma patients. METHODS: Retrospective analysis of a prospective data base conducted on uncontrolled glaucoma patients who underwent BISIXEN surgery. Primary endpoint measure was the incidence of sight-threatening complications. Secondary endpoints included intraocular pressure (IOP) reduction and in number of required antiglaucoma medications. RESULTS: Ten patients (20 eyes) were included in the analysis. Median (95% confidence interval) follow-up was 12.0 (7.0-12.0) months, with 14 eyes having a follow-up of 12 months. No sight-threatening complications, such as endophthalmitis, retinal detachment, corneal decompensation, or intraocular hemorrhages were observed in any eye of study sample. Mean IOP decreased significantly from 25.2 (21.5-28.9) mm Hg at baseline to 15.1 (13.4-16.8) mm Hg at the last follow-up visit (p = 0.0001). Mean number of antiglaucoma medications was significantly reduced from 2.9 (2.5 to 3.3) drugs at baseline to 0.40 (0.00-0.70) at the end of the study (p < 0.0001). At the last study visit, 14 (70.0%) eyes had an IOP ≥ 6 and ≤ 18 mm Hg without treatment. Two eyes needed surgical revision and three ones needed a new glaucoma surgery: two underwent Ahmed valves (one eye with aniridia and the other previously operated on) and one underwent non-penetrating deep sclerectomy. CONCLUSIONS: Bilateral simultaneous XEN implantation may be a feasible strategy in those patients with high anesthetic risk.

Optimization of Diabetic Macular Edema Management in the Real World: A Model of Excellence in Retina Units: The EMUREX Initiative.

PURPOSE: To define and develop a model of excellence for the clinical management of diabetic macular edema (DME) patients in a real-world setting. METHODS: A multidisciplinary joint commission (5 ophthalmologists, 1 nurse, and 1 pharmaceutic) established a series of preliminary recommendations based on clinical guidelines and DME activity results from 8 Pilot Hospitals (PH). These were validated by members of each PH and a group of DME patients in discussion workshops. Thus, the validated guideline (VG) took into consideration different aspects, namely, main core points (ranging 0-100), criteria, and indicators. Finally, each PH own setting was compared to the VG in order to settle down a starting point to clinical excellence. RESULTS: Mean PH score was 51.5 (range 30-65). As compared to their maximum, main points that showed best scores were Clinical Guidelines and Protocols (78%) and Portfolio of Services (73%). Topics reaching close to 50% scoring included Resources (55%), Innovation (54%), Care Process (53%), Organization (52%), and Leadership (50%). Lowest scores were observed in the Strategic Alliances (46%) and Staff (37%) points. CONCLUSIONS: Analysis of each PH by the VG delivered a global vision of the starting situation, especially focused in the identification of the different improvement areas. In order to further extend this model into the Public Health System, the effect of implementing it in different hospitals should be assessed to analyze its impact on daily clinical practice and health economics.

Author Correction: A new approach based on targeted pooled DNA sequencing identifies novel mutations in patients with Inherited Retinal Dystrophies.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

A new approach based on targeted pooled DNA sequencing identifies novel mutations in patients with Inherited Retinal Dystrophies.

Inherited retinal diseases (IRD) are a heterogeneous group of diseases that mainly affect the retina; more than 250 genes have been linked to the disease and more than 20 different clinical phenotypes have been described. This heterogeneity both at the clinical and genetic levels complicates the identification of causative mutations. Therefore, a detailed genetic characterization is important for genetic counselling and decisions regarding treatment. In this study, we developed a method consisting on pooled targeted next generation sequencing (NGS) that we applied to 316 eye disease related genes, followed by High Resolution Melting and copy number variation analysis. DNA from 115 unrelated test samples was pooled and samples with known mutations were used as positive controls to assess the sensitivity of our approach. Causal mutations for IRDs were found in 36 patients achieving a detection rate of 31.3%. Overall, 49 likely causative mutations were identified in characterized patients, 14 of which were first described in this study (28.6%). Our study shows that this new approach is a cost-effective tool for detection of causative mutations in patients with inherited retinopathies.

A 5-Year Follow-Up Study of the Treatment of Macular Edema Due to Retinal Vein Occlusion Using Dexamethasone Intravitreal Implants.

PURPOSE: To evaluate the long-term effects of intravitreal dexamethasone implants (IDIs) in eyes with macular edema (ME) due to retinal vein occlusion (RVO). METHODS: We reviewed the records of 10 patients followed for 5 years after they received their first IDI. The main outcome measures included changes in best corrected visual acuity (BCVA), central macular thickness (CMT), and central macular volume (CMV), and the incidence of side effects. RESULTS: Ten patients were included in the study with a mean follow-up of 65.51 months. Forty IDI injections were performed. An improvement in BCVA was observed after 92.5% of the IDI injections (P < 0.05), while the CMT and the CMV decreased significantly (P < 0.05) after 97.5% of the injections. After 27.5% of the injections, the intraocular pressure rose more than 10 mmHg and 3 of the 7 phakic patients required phacoemulsification surgery. CONCLUSION: IDI is an effective therapy for the treatment of ME secondary to RVO with a favorable long-term safety profile.

Dabrafenib for cutaneous melanoma infiltrating the vitreous: regression of metastasis and occurrence of uveitis as a secondary effect.

Intraocular metastasis of cutaneous melanoma is extremely infrequent. This typically occurs in advanced metastatic disease and has a poor survival prognosis. The most frequent reported treatment is radiotherapy. BRAF inhibitors are new, orally administered and very effective drugs used for metastatic cutaneous melanoma. Herein, we report a case of a 58-year-old patient with a recent diagnosis of cutaneous melanoma who consulted for floaters and presented vitreous opacities in both eyes. A diagnostic vitrectomy of his left eye was performed and pathologic analysis disclosed infiltrating melanoma cells in the vitreous. Treatment with dabrafenib (a type of BRAF inhibitor) achieved the regression of the intraocular metastasis in the right eye. Moreover, the patient presented a severe anterior uveitis due to dabrafenib, a well-known secondary effect of this drug.