Feasibility assessment of the Eye Scan Ultrasound System for cataract characterization and optimal phacoemulsification energy estimation: protocol for a pilot, nonblinded and monocentre study.

BACKGROUND: Cataracts are lens opacifications that are responsible for more than half of blindness cases worldwide, and the only treatment is surgical intervention. Phacoemulsification surgery, the most frequently performed cataract surgery in developed countries, has associated risks, some of which are related to excessive phacoemulsification energy levels and times. The protocol proposed in herein will be used to evaluate the feasibility of a new experimental medical device, the Eye Scan Ultrasound System (ESUS), for the automatic classification of cataract type and severity and quantitative estimation of the optimal phacoemulsification energy. METHODS: The pilot study protocol will be used to evaluate the feasibility and safety of the ESUS in clinical practice. The study will be conducted in subjects with age-related cataracts and on healthy subjects as controls. The procedures include data acquisition with the experimental ESUS, classification based on the Lens Opacity Classification System III (LOCS III, comparator) using a slit lamp, contrast sensitivity test, optical coherence tomography, specular microscopy and surgical parameters. ESUS works in A-scan pulse-echo mode, with a central frequency of 20 MHz. From the collected signals, acoustic parameters will be extracted and used for automatic cataract characterization and optimal phacoemulsification energy estimation. The study includes two phases. The data collected in the first phase (40 patients, 2 eyes per patient) will be used to train the ESUS algorithms, while the data collected in the second phase (10 patients, 2 eyes per patient) will be used to assess the classification performance. System safety will be monitored during the study. DISCUSSION: The present pilot study protocol will evaluate the feasibility and safety of the ESUS for use in clinical practice, and the results will support a larger clinical study for the efficacy assessment of the ESUS as a diagnostic tool. Ultimately, the ESUS is expected to represent a valuable tool for surgical planning by reducing complications associated with excessive levels of phacoemulsification energy and surgical times, which will have a positive impact on healthcare systems and society. The study is not yet recruiting. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04461912 , registered on July 8, 2020.

Efficacy and Safety of Intravitreal Aflibercept Treat and Extend for Polypoidal Choroidal Vasculopathy in the ATLANTIC Study: A Randomized Clinical Trial.

IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. METHODS: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). RESULTS: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study. TRIAL REGISTRATION: The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20.

Polypoidal Choroidal Vasculopathy in Caucasians: Morphological Findings from Multimodal Retinal Imaging.

PURPOSE: The aim of the study was to characterize the morphological features of polypoidal choroidal vasculopathy (PCV) in a large Caucasian population. METHODS: We conducteda multicenter, cross-sectional study of treatment-naïve patients with PCV. Baseline fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA) were assessed by trained medical graders. Typical PCV features were explored, and retinal thickness (RT) and choroidal thickness (CT) measurements were performed. RESULTS: Seventy-nine eyes of 73 patients (mean age, 72.6 ± 11.9 years) were included. ICGA identified macular polyps in 89.9% of cases. SD-OCT revealed mostly subretinal fluid (93.6%) and a retinal pigment epithelium (RPE) detachment in 91.4%, with sharp protrusion in 67.0% of cases. Polyp-like structures were seen in 74.3% of cases, mostly adherent to an elevated RPE (69.6%). Type 1 neovascularization (NV) was identified in 74.7% of patients, while 16.5% had a mixed NV. The mean macular CT was 220.9 ± 83.2 µm (range, 67.9-403.6). Diffuse and focal pachychoroid were observed in 26.6 and 30.4% of patients, respectively. Soft drusen were reported in 62.0% of cases, but retinal hemorrhage occurred in only 19.0% of cases. CONCLUSION: The morphological features of PCV in Caucasians are similar to those reported in Asians. Pachychoroid signs were found in nearly half of our cohort. However, the mean age at presentation, high prevalence of soft drusen, and low prevalence of large subretinal hemorrhages make PCV closer to age-related macular degeneration in this ethnic group.

T and genetic variations between Asian and Caucasian polypoidal choroidal vasculopathy.

PURPOSE: To compare phenotypic and genetic variations in polypoidal choroidal vasculopathy (PCV) between Caucasian and Asian patients. METHODS: We analysed phenotypic and genotypic data from two sites, Association for Innovation and Biomedical Research on Light and Image, Portugal and Singapore National Eye Centre, Singapore. Baseline fundus photography, spectral domain-optical coherence tomography, indocyanine green and fluorescein angiography scans were analysed by respective reading centres using a standardised grading protocol. Single nucleotide polymorphisms across 8 PCV loci were compared between cases and controls selected from each population. RESULTS: One hundred and forty treatment-naïve PCV participants (35 Portuguese and 105 Singaporean) were included. The Portuguese cohort were older (72.33±8.44 vs 68.71±9.40 years, p=0.043) and were comprised of a lower proportion of males (43% vs 71%, p=0.005) compared with the Singaporean cohort. Differences in imaging features include higher prevalence of soft drusen (66% vs 30%, p=0.004), lower prevalence of subretinal haemorrhage (14% vs 67%, p<0.001), smaller polypoidal lesion (PL) area (0.09±0.09 vs 0.76±0.93 mm2, p<0.001), lower ratio of PL to branching vascular network area (3% vs 38%, p<0.001) and lower central retinal thickness (346.48±93.74 vs 493.16±212.92 µm, p<0.001) in the Portuguese cohort. CETP rs3764261 (OR 2.467; 95% CI 1.282 to 4.745, p=0.006) in the Portuguese population was significantly associated with PCV and CFH rs800292 (OR 1.719; 95% CI 1.139 to 2.596, p=0.010) in the Singaporean population, respectively. CONCLUSION: Among Asian and Caucasian patients with PCV, there are significant differences in the expression of phenotype. We also identified different polymorphisms associated with PCV in the two populations.

Adherence to a Mediterranean diet, lifestyle and age-related macular degeneration: the Coimbra Eye Study - report 3.

PURPOSE: To characterize the lifestyle and nutritional risk profile associated with the Mediterranean diet in a Portuguese population with and without age-related macular degeneration (AMD). METHODS: Nested case-control study (n = 883) within the Coimbra Eye Study, including 434 subjects with AMD and 449 age- and sex-matched subjects without AMD. All enrolled subjects underwent a full risk assessment, including lifestyle-related risk factors and a thorough food frequency questionnaire. This allowed us to build an adherence score to the Mediterranean diet (mediSCORE, range 0-9) constructed from individual food intakes. Food intake was also further analysed by conversion to micronutrient consumption. RESULTS: Our results suggest that physical activity has a protective role in AMD [p = 0.018 after multivariate adjustment, OR: 0.69 (0.51-0.93)]. High (mediSCORE ≥6) was also found to be protective [p = 0.041, OR: 0.62 (95% CI: 0.38-0.97)]. Food group analysis unveiled a specific protective role for increased fruits consumption (p = 0.029). Finally, micronutrient analysis revealed a protective role associated with increased consumption of caffeine, fibres, beta-carotene, vitamin C and vitamin E (p < 0.05). CONCLUSION: High mediSCORE appears to confer protection against the development of AMD in a Mediterranean population. This effect is driven by increased consumption of fruits and some antioxidant micronutrients, which emerged as statistically significant protective factors. Further studies are required to establish dietary recommendations with clinical application.

Systemic and Ocular Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in the European Eye Epidemiology (E3) Population.

PURPOSE: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. DESIGN: Cross-sectional meta-analysis. PARTICIPANTS: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9±12.3-82.1±4.2 years) of the European Eye Epidemiology (E3) consortium. METHODS: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. MAIN OUTCOME MEASURES: Determinants of pRNFLT. RESULTS: Mean pRNFLT ranged from 86.8±21.4 µm in the Rotterdam Study I to 104.7±12.5 µm in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (ß = -0.38 µm/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (IOP) (ß = -0.36 µm/mmHg; 95% CI, -0.56 to -0.15), visual impairment (ß = -5.50 µm; 95% CI, -9.37 to -1.64), and history of systemic hypertension (ß = -0.54 µm; 95% CI, -1.01 to -0.07) and stroke (ß = -1.94 µm; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (ß = -3.11 µm; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (ß = 1.39 µm/diopter; 95% CI, 1.19-1.59) and smoking (ß = 1.53 µm; 95% CI, 1.00-2.06 for current smokers compared with never-smokers). CONCLUSIONS: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities.

Adherence to a Mediterranean diet and its association with age-related macular degeneration. The Coimbra Eye Study-Report 4.

OBJECTIVES: This study aimed to characterize the association of lifestyle and nutritional risk profiles with age-related macular degeneration (AMD) in two subpopulations with differing AMD prevalence. METHODS: This case-control study (n = 1992) included 768 patients with AMD and 1224 age- and sex-matched participants without AMD with a single visit at a primary health care unit. Enrolled participants completed a validated lifestyle and food frequency questionnaire. A score to measure adherence to the Mediterranean diet (mediSCORE; Range, 0-9) was constructed from individual food intakes, which were further analyzed by conversion to nutrient consumption. RESULTS: Higher adherence to the Mediterranean diet (mediSCORE ≥6) was significantly associated with no AMD (odds ratio [OR] = 0.73; P = 0.009). The subpopulation with lower AMD prevalence presented significantly higher adherence to the Mediterranean diet in relation to all individual food groups that comprised the mediSCORE (P < 0.014) with the exception of cereals. Food group analysis showed significant associations between the increased consumption of vegetables (OR = 0.63; P < 0.001) and fruit and nuts (OR = 0.78; P = 0.010) with no AMD. Nutrient analysis revealed that an increased ingestion of water, fibers, total fat, monounsaturated and polyunsaturated fatty acids, linoleic acid, vitamins A and C, carotene, alpha-tocopherol, folate, magnesium, iron, and zinc were significantly associated with no AMD (P < 0.0013). Finally, regular physical activity was associated with no AMD (P = 0.003). CONCLUSIONS: High adherence to a Mediterranean diet and regular physical activity seem to be protective factors for AMD in a Portuguese population. The effect of the diet is likely driven by the increased consumption of vegetables, fruits, and nuts.

Ranibizumab Plus Panretinal Photocoagulation versus Panretinal Photocoagulation Alone for High-Risk Proliferative Diabetic Retinopathy (PROTEUS Study).

PURPOSE: Comparison of the efficacy of ranibizumab (RBZ) 0.5 mg intravitreal injections plus panretinal photocoagulation (PRP) versus PRP alone in the regression of the neovascularization (NV) area in subjects with high-risk proliferative diabetic retinopathy (HR-PDR) over a 12-month period. DESIGN: Prospective, randomized, multicenter, open-label, phase II/III study. PARTICIPANTS: Eighty-seven participants (aged ≥18 years) with type 1/2 diabetes and HR-PDR (mean age, 55.2 years; 37% were female). METHODS: Participants were randomized (1:1) to receive RBZ+PRP (n = 41) or PRP monotherapy (n = 46). The RBZ+PRP group received 3 monthly RBZ injections along with standard PRP. The PRP monotherapy group received standard PRP between day 1 and month 2; thereafter, re-treatments in both groups were at the investigators' discretion. MAIN OUTCOME MEASURES: The primary outcome was regression of NV total, on the disc (NVD) plus elsewhere (NVE), defined as any decrease in the area of NV from the baseline to month 12. Secondary outcomes included best-corrected visual acuity (BCVA) changes from baseline to month 12, time to complete NV regression, recurrence of NV, macular retinal thickness changes from baseline to month 12, need for treatment for diabetic macular edema, need for vitrectomy because of occurrence of vitreous hemorrhage, tractional retinal detachment or other complications of DR, and adverse events (AEs) related to treatments. RESULTS: Seventy-seven participants (88.5%) completed the study. Overall baseline demographics were similar for both groups, except for age. At month 12, 92.7% of participants in the RBZ+PRP group presented NV total reduction versus 70.5% of the PRP monotherapy participants (P = 0.009). The number of participants with NVD and NVE reductions was higher with RBZ+PRP (93.3% and 91.4%, respectively) versus PRP (68.8% and 73.7%, respectively), significant only for NVE (P = 0.048). Complete NV total regression was observed in 43.9% in the RBZ+PRP group versus 25.0% in the PRP monotherapy group (P = 0.066). At month 12, the mean BCVA was 75.2 letters (20/32) in the RBZ+PRP group versus 69.2 letters (20/40) in the PRP monotherapy group (P = 0.104). In the RBZ+PRP group, the mean number of PRP treatments over month 12 was 3.5±1.3, whereas in the PRP monotherapy group, it was 4.6±1.5 (P = 0.001). No deaths or unexpected AEs were reported. CONCLUSIONS: Treatment with RBZ+PRP was more effective than PRP monotherapy for NV regression in HR-PDR participants over 12 months.

Protocol for a randomised, double-masked, sham-controlled phase 4 study on the efficacy, safety and tolerability of intravitreal aflibercept monotherapy compared with aflibercept with adjunctive photodynamic therapy in polypoidal choroidal vasculopathy: the ATLANTIC study.

PURPOSE: The purpose of this study is to compare the efficacy and safety of intravitreal aflibercept (IVA) with sham photodynamic therapy (sPDT) versus IVA with verteporfin PDT (vPDT) in a Caucasian population with treatment-naive polypoidal choroidal vasculopathy (PCV), enrolling into a treat and extend (T&E) regimen. METHODS AND ANALYSIS: Randomised, double-masked, sham-controlled, multicentre phase 4 investigator-driven clinical trial. The primary outcomes are (1) change in best-corrected visual acuity (BCVA) from baseline and (2) polyp regression at week 52, assessed by indocyanine green angiography (ICGA). Fifty patients with treatment-naive PCV will be recruited from Portuguese and Spanish clinical sites. Eligible patients will receive monthly IVA for 3 months (week 0, week 4 and week 8). At week 16, all patients will repeat ICGA and undergo central randomisation (1:1 ratio) into one of the following groups: Group 1-IVA T&E + vPDT; Group 2-IVA T&E + sPDT. PDT will be performed at week 16, week 28 and week 40 in the presence of active polyps. After week 16, the presence of macular fluid on optical coherence tomography will determine the schedule of observations. When present, the interval between visits/injections will decrease 2 weeks (minimum 6 weeks). When not, the interval between visits/injections will increase 2 weeks (maximum 12 weeks). Efficacy will be evaluated based on BCVA, central retinal thickness and polyp regression. Safety parameters will include assessment of intraocular pressure, adverse events and serious adverse events. ETHICS AND DISSEMINATION: This study was designed and shall be implemented and reported in accordance with the International Conference on Harmonisation (ICH) Harmonised Tripartite Guidelines for Good Clinical Practice, with applicable local regulations and with the ethical principles laid down in the Declaration of Helsinki. The study received approval from Comissão de Ética para a Investigação Clínica and Comité Ético de investigación Clínica del Hospital Universitari de Bellvitge. TRIAL REGISTRATION NUMBER: This study is registered under the EudraCT number: 2015-001368-20 and the ClinicalTrials.gov Identifier: NCT02495181.

Age-related macular degeneration in Portugal: prevalence and risk factors in a coastal and an inland town. The Coimbra Eye Study - Report 2.

PURPOSE: To determine the age- and sex-specific prevalence of early and late age-related macular degeneration (AMD) in two Portuguese population-based samples and to identify its risk factors. POPULATION: A population of 6023 adults aged ≥55 years was recruited from two Portuguese primary healthcare units in the central region of Portugal - one from a coastal (n = 3000) and another from an inland town (n = 3023). METHODS: Cross-sectional population-based study. Participants were enrolled in the two locations between August 2009 and October 2013. Responders underwent standardized interviews and ophthalmologic examination, including digital fundus imaging. All fundus photographs were graded according to an International Classification and Grading System. The main outcome measures consisted of age- and sex-adjusted prevalence of early and late AMD. Potential epidemiologic risk factors were also evaluated using logistic regression analysis. RESULTS: Of the 6023 subjects enrolled, 5996 had gradable fundus images and were included in the analysis. The crude prevalence of early and late AMD was 6.99 and 0.67%, respectively, for the coastal town and 15.39 and 1.29% for the inland town. Age- and sex-adjusted prevalence of any AMD for the Portuguese population was 12.48% (95% CI: 11.61-13.33) with late AMD accounting for 1.16% (95% CI: 0.85-1.46). Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.55% (95% CI: 0.36-0.75) and 0.61% (95% CI: 0.37-0.84) of individuals, respectively. After adjusting for possible confounding factors, prevalence of early and late AMD increased with increasing age (OR = 1.35; 95% CI: 1.23-1.49 for early and OR = 3.01; 95% CI: 2.22-4.08 for late AMD, per each decade of age increase, p < 0.001). After adjustment for age, sex, family history, smoking history, hypertension, diabetes and BMI, subjects from the inland town presented a significantly higher OR of early and late AMD than subjects from the coastal town (OR = 2.57, 95% CI: 2.12-3.12, p < 0.001 for early and OR = 2.06, 95% CI: 1.07-3.95, p = 0.029 for late AMD). CONCLUSIONS: The prevalence of early and late AMD in this Portuguese population was similar to other large-scale population-based cohorts. After controlling for confounders, age and study site of inclusion were significant independent predictors for both early and late forms of the disease. Further analysis will be needed to completely unravel the underlying reasons for this difference regarding geographic location.

Ranibizumab for High-Risk Proliferative Diabetic Retinopathy: An Exploratory Randomized Controlled Trial.

PURPOSE: To compare the efficacy and safety of intravitreal ranibizumab (IVR) in monotherapy or associated with panretinal photocoagulation (PRP) versus conventional PRP, for high-risk proliferative diabetic retinopathy (PDR) without vitreoretinal traction. PROCEDURES: Multicenter randomized trial, with 3 treatment arms: PRP versus IVR alone and PRP + IVR combined treatment. Follow-up was performed at months 3, 6 and 12. RESULTS: Thirty-five subjects were randomized and 32 used for analysis. Complete regression of neovessels elsewhere occurred in 100% (PRP + IVR), 75% (IVR) and 69.2% (PRP) and for neovessels of the disk in 44.4% (PRP + IVR), 37.5% (IVR) and 30.8% (PRP). During the 1-year duration of treatment, there was no need for laser rescue treatment in IVR-treated eyes. CONCLUSIONS: This trial suggests that the use of IVR is safe and may have a beneficial effect in the treatment of eyes with high-risk PDR. MESSAGE: Ranibizumab appears to have a place in the treatment of PDR.

Relevance of Retinal Thickness Changes in the OCT Inner and Outer Rings to Predict Progression to Clinical Macular Edema: An Attempt of Composite Grading of Macular Edema.

PURPOSE: To characterize the relevance of macular thickness changes in the inner and outer rings in the progression of macular edema in eyes/patients with diabetes type 2. METHODS: A total of 374 type 2 diabetic patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20-35) were included in a 12-month prospective observational study to identify retinopathy progression. Retinal thickness analyses were performed in 194 eyes/patients using Cirrus SD- OCT and 166 eyes/patients using Spectralis SD-OCT. The DRCR.net classification of subclinical and clinical macular edema was used. A composite grading of macular edema is proposed in this study. RESULTS: A total of 317 eyes/patients completed the study. SD-OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Increased thickness of the central subfield is the best predictor for the development of clinical macular edema, with 85.7% sensitivity and 71.9% specificity (OR: 2.57, 95% CI: 0.82-7.99). However, the involvement of the inner and outer rings is a cumulative predictor of progression to clinical macular edema (OR: 8.69, 95% CI: 2.85-26.52). CONCLUSIONS: A composite OCT grading of macular edema taking into account the retinal thickness changes in the inner and outer macular rings offers a simple way to characterize macular edema, with added clinical value.

Retinal layer location of increased retinal thickness in eyes with subclinical and clinical macular edema in diabetes type 2.

PURPOSE: To identify the retinal layer predominantly affected in eyes with subclinical and clinical macular edema in diabetes type 2. METHODS: A cohort of 194 type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (ETDRS levels 20/35) were examined with Cirrus spectral-domain optical coherence tomography (OCT) at the baseline visit (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers of the eyes with subclinical and clinical macular edema was compared with a sample of 31 eyes from diabetic patients with normal OCT and an age-matched control group of 58 healthy eyes. RESULTS: From the 194 eyes in the study, 62 had subclinical macular edema and 12 had clinical macular edema. The highest increases in retinal thickness (RT) were found in the inner nuclear layer (INL; 33.6% in subclinical macular edema and 81.8% in clinical macular edema). Increases were also found in the neighboring layers. Thinning of the retina was registered in the retinal nerve fiber, ganglion cells and inner plexiform layers in the diabetic eyes without macular edema. CONCLUSIONS: The increase in RT occurring in diabetic eyes with macular edema is predominantly located in the INL but extends to neighboring retinal layers indicating that it may be due to extracellular fluid accumulation.

One-year progression of diabetic subclinical macular edema in eyes with mild nonproliferative diabetic retinopathy: location of the increase in retinal thickness.

PURPOSE: To characterize the 1-year progression of retinal thickness (RT) increase occurring in eyes with subclinical macular edema in type 2 diabetes. METHODS: Forty-eight type 2 diabetic eyes/patients with mild nonproliferative diabetic retinopathy (NPDR; levels 20 and 35 in the Early Treatment Diabetic Retinopathy Study) classified as presenting subclinical macular edema at baseline completed the 1-year follow-up period, from a sample of 194 followed in a 12-month observational and prospective study (ClinicalTrials.gov identifier: NCT01145599). Automated segmentation of the retinal layers in these eyes was performed, followed by verification and correction by a human grader. RESULTS: The highest increase in RT over the 1-year follow-up period for the 48 eyes/patients with subclinical macular edema was found in the inner nuclear layer (INL). Progression to clinical macular edema was also associated with increased thickening of other retinal layers aside from the INL. The microvascular disease activity shown by microaneurysm (MA) turnover ≥6 was associated with progression from subclinical to clinical macular edema. CONCLUSIONS: Increases in RT occurring over a period of 1 year in diabetic eyes with mild NPDR and subclinical macular edema occur mainly in the INL. The development of clinical macular edema appears to be associated with increased thickening of other retinal layers and microvascular disease activity.

Progression of myopic maculopathy after treatment of choroidal neovascularization.

PURPOSE: To evaluate the long-term progression of myopic maculopathy and functional outcome after treatment of myopic choroidal neovascularization (CNV) with photodynamic therapy (PDT) and/or intravitreal ranibizumab (IVR). METHODS: Retrospective study with a cross-sectional evaluation. Eyes were assigned to 4 groups (PDT, IVR, PDT + IVR, dry myopic maculopathy) and evaluated with best-corrected visual acuity, color fundus photography and spectral-domain optical coherence tomography. Chorioretinal atrophy progression was quantified. RESULTS: Fifty-four eyes were included with a mean follow-up of 80.6 ± 28.0 months. The prevalence of diffuse, patchy and macular atrophy increased during the follow-up, in contrast with tessellated fundus, lacquer cracks and active CNV. Progression of macular atrophy was significant in the 3 treatment groups (p < 0.05) and predictive of visual acuity. It depended on age, degree of myopia and presence of staphyloma, but not on the type of treatment. CONCLUSIONS: The long-term functional outcome of eyes with myopic CNV is more dependent on the progression of macular atrophy, and not on the type of treatment.

Choroidal thickness in diabetic retinopathy: the influence of antiangiogenic therapy.

PURPOSE: To analyze the effect of anti-vascular endothelial growth factor agents (anti-VEGF) in submacular choroidal thickness (CT) of diabetic retinopathy (DR) patients. METHODS: Cross-sectional study, which included 25 DR patients (50 eyes) divided in 2 groups, according to DR stage and previous treatments: nonproliferative DR and diffuse diabetic macular edema in both eyes, submitted to macular laser in both eyes and anti-VEGF injection only in 1 eye (nonproliferative diabetic retinopathy + diabetic macular edema group, n = 11); and proliferative DR in both eyes, treated with panretinal photocoagulation in both eyes and anti-VEGF injection only in 1 eye (proliferative diabetic retinopathy group, n = 14). In the study visit, all patients underwent optical coherence tomography with enhanced depth imaging protocol. Choroidal segmentation was performed manually. The medium CT in central macular area (CCT) and the CT in centrofoveal B-scan were obtained automatically. RESULTS: The 25 eyes treated with anti-VEGF showed a reduction on CCT (P = 0.002) and subfoveal CT (P = 0.004), compared with the fellow eyes treated with laser only. Independent evaluation of PDR group revealed similar results (CCT, P = 0.02; subfoveal CT, P = 0.03). In nonproliferative diabetic retinopathy + diabetic macular edema group, CCT was also significantly thinner in eyes treated with anti-VEGF (P = 0.04). A correlation between the number of injections and a thinner CT was found in this group (P = 0.03) and in the evaluation of all eyes together (P = 0.03). CONCLUSION: Diabetic eyes treated with anti-VEGF agents have reduced CT.

Degree of decrease in central retinal thickness predicts visual acuity response to intravitreal ranibizumab in diabetic macular edema.

PURPOSE: To characterize factors that may be associated with optimal or suboptimal response to ranibizumab intravitreal injections in diabetic macular edema (DME). METHODS: Fifty-nine eyes with DME treated with ranibizumab were included. All underwent best-corrected visual acuity (BCVA) assessment and optical coherence tomography (OCT) at baseline, 3 and 6 months. Central retinal thickness (CRT) was assessed at each visit, and OCT images were classified according to their morphological patterns. RESULTS: A mean BCVA increase of 4.78 and 5.52 letters, and a CRT decrease of 80.25 and 106.12 µm were found after 3 and 6 months of treatment (p < 0.001). BCVA improvement was found to be dependent on baseline BCVA and the degree of CRT decrease. Twenty-six eyes (44%) showing a CRT decrease ≥ 20% improved BCVA by 10.3 ± 13.0 letters, whereas 33 eyes (56%) with a CRT decrease <20% had BCVA improvement of 1.8 ± 7.2 letters (odds ratio = 3.31). CONCLUSIONS: The degree of CRT decrease obtained by spectral-domain OCT identifies well the optimal responders to intravitreal ranibizumab and predicts BCVA improvement after treatment.

Subclinical macular edema as a predictor of progression to clinically significant macular edema in type 2 diabetes.

OBJECTIVE: To examine the relationship between subclinical diabetic macular edema (DME) and the development of clinically significant macular edema (CSME) in nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes. METHODS: A prospective, monocenter, observational study was designed to follow patients/eyes with type 2 diabetes and NPDR (Early Treatment Diabetic Retinopathy Study levels 20 and 35) with no prior laser treatment for 2 years or until development of CSME. Ophthalmologic examinations, including best-corrected visual acuity, fundus photography and optical coherence tomography (OCT), were performed at baseline, 6 months and a final visit. RESULTS: A total of 348 patients completed study follow-up; 26 eyes developed CSME. Six out of 32 eyes/patients presenting subclinical DME at baseline developed CSME (18.7%), while 20 out of 316 eyes without subclinical DME developed CSME (6.3%). Eyes/patients with subclinical DME presented a risk for DME progression 3.686 times higher than that of eyes/patients without subclinical DME (95% confidence interval 1.221-7.988). CONCLUSIONS: Subclinical DME in eyes with NPDR identified by center point thickness measured on a Stratus OCT is a good predictor of CSME development.

Choroidal thickness after treatment for myopic choroidal neovascularization.

PURPOSE: To evaluate choroidal thickness in highly myopic eyes with choroidal neovascularization (CNV), 3 or more years after treatment with photodynamic therapy (PDT), intravitreal ranibizumab (IVR), or both (PDT + IVR). METHODS: The medical records of patients with high myopia and CNV treated with PDT or IVR in our department were reviewed. Eyes meeting the inclusion criteria were assigned to 3 groups: PDT, IVR, and PDT + IVR. A fourth group, "dry myopic maculopathy," included the contralateral highly myopic eyes that never developed CNV. All patients performed a cross-sectional evaluation with best-corrected visual acuity (BCVA), measurement of axial length, color fundus photography, and enhanced depth imaging with spectral domain optical coherence tomography. RESULTS: Forty-two eyes (21 patients) were included: 11 eyes (26.2%) in the PDT group, 8 (19.0%) in the IVR group, 9 (21.4%) in the PDT + IVR group, and 14 (33.3%) in the dry maculopathy group. Subfoveal choroidal thickness showed no significant differences between groups (p>0.05). Positive correlation was found between BCVA and macular choroidal thickness (r = +0.293, p<0.001). Regression analysis showed that age (p<0.001), axial length (p<0.001), sex (p = 0.001), and myopic lesions such as tessellated fundus (p = 0.046) and patchy atrophy (p = 0.008) were predictive of choroidal thickness. Type of treatment was not predictive of choroidal thickness. CONCLUSIONS: Older age and greater axial length are the major factors associated with macular choroidal thinning in highly myopic eyes submitted to CNV treatment. The type of treatment performed for myopic CNV had no predictive contribution for choroidal thickness.

Three different phenotypes of mild nonproliferative diabetic retinopathy with different risks for development of clinically significant macular edema.

PURPOSE: To identify different phenotypes of nonproliferative diabetic retinopathy (NPDR) and their progression to clinically significant macular edema (CSME). METHODS: A prospective observational study was designed to follow eyes/patients with diabetes type 2 and NPDR with no prior laser treatment for 2 years or until development of CSME. A total of 410 patients, one eye per patient, fulfilled the inclusion/exclusion criteria and were included in the study. Ophthalmological examinations, including BCVA, fundus photography with Retmarker analysis, and optical coherence tomography (OCT), were performed at baseline, month 6 and month 24, or before laser treatment. Hierarchical cluster analysis was used to identify homogeneous subgroups and clinically significant thresholds of the data collected. RESULTS: A total of 376 eyes/patients performed the 6-month visit and were considered for cluster analysis. This mathematical method identified three different phenotypes based on statistically significant differences for the microaneurysm (MA) turnover and for the central retinal thickness (RT): phenotype A (low MA turnover and normal RT, 48.1%); phenotype B (low MA turnover and increased central RT, 23.2%); and phenotype C (high MA turnover, 28.7%). From the 348 eyes/patients that reached the study end point or completed the 24-month visit, 26 developed CSME: 3 from phenotype A (1.8%), 7 from phenotype B (8.5%), and 16 from phenotype C (16.2%). Eyes/patients from phenotype C showed a higher risk for CSME development (OR = 3.536; P < 0.001). CONCLUSIONS: Hierarchical cluster analysis identifies three different phenotypes of NPDR based on MA turnover and central macular thickness. Eyes/patients from phenotype C show a higher risk for the development of CSME. (ClinicalTrials.gov number, NCT00763802.)