Characterization of central-involved diabetic macular edema using OCT and OCTA.

PURPOSE: To characterize the occurrence of diabetic macular edema and the presence of abnormal retinal fluid accumulation in nonproliferative diabetic retinopathy (NPDR). METHODS: In this two-year prospective study, a total of 122 eyes with diabetes type 2 underwent optical coherence tomography (OCT) and OCT-Angiography in association with OCT-Fluid imaging, a novel algorithm of OCT analysis allowing quantification of abnormal accumulation of fluid in the retina through low optical reflectivity ratios (LOR). Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment was performed using 7-field color fundus photography. Best corrected visual acuity was also recorded. RESULTS: During the 2-year follow-up, 23 eyes (19%) developed central-involved diabetic macular edema (CI-DME) and 2 eyes (2%) developed clinically significant macular edema (CSME). In the two-year period of the study, eyes that developed CI-DME showed a progressive increase in central retinal thickness (CRT) (ß = 7.7 ± 2.1 µm/year, p < 0.001) and in LOR values (ß = 0.009 ± 0.004 ratio/year, p = 0.027). The increase in CRT and abnormal retinal fluid, represented by increased LOR ratios, are associated with increased retinal perfusion in the deep capillary plexus (DCP) (skeletonized vessel density, p = 0.039). In contrast, the eyes with CSME showed decreased retinal perfusion and abnormal fluid located in the outer layers of the retina. CONCLUSIONS: CI-DME and CSME appear to represent different entities. Eyes with CI-DME show increases in abnormal retinal fluid associated with increased retinal vascular perfusion in the DCP. Eyes with CSME are apparently associated with decreased retinal vascular perfusion in the DCP and abnormal fluid in the outer retina.

The influence of personality on the quality of vision after multifocal intraocular lens implantation.

OBJECTIVE: To assess the possible correlation between patients' personality traits and subjective perception of quality of vision (QoV), after multifocal intraocular lens (mIOL) implantation. METHODS: patients who had bilateral implantation of a non-diffractive X-WAVE or a trifocal lens were assessed 6 months postoperatively. Patients answered the NEO-Five Factor Inventory (NEO-FFI-20) questionnaire ("Big Five five-factor personality model") to examine their personality. Six months following surgery, patients were asked to fill a QoV questionnaire where they graded the frequency of 10 common visual symptoms. Primary outcomes were to evaluate the correlation between personality scores and the reported frequency of visual disturbances. RESULTS: The study comprised 20 patients submitted to bilateral cataract surgery, 10 with a non-diffractive X-WAVE lens (AcrySof® IQ Vivity) and 10 with a trifocal lens (AcrySof® IQ PanOptix). Mean age was 60.23 (7.06) years. Six months following surgery, patients with lower scores of conscientiousness and extroversion reported a higher frequency of visual disturbances (blurred vision, P = .015 and P = .009, seeing double images P = .018 and P = .006, and having difficulties focusing, P = .027 and P = .022, respectively). In addition, patients with high neuroticism scores had more difficulty focusing (P = .033). CONCLUSIONS: In this study, personality traits such as low conscientiousness and extroversion and high neuroticism significantly influenced QoV perception 6 months after bilateral multifocal lens implantation. Patients' personality questionnaires could be a useful preoperative assessment test to a mIOL.

Retinal neurodegeneration in eyes with NPDR risk phenotypes: A two-year longitudinal study.

INTRODUCTION: Diabetic retinopathy (DR) is both a microangiopathy and a neurodegenerative disease. However, the connections between both changes are not well known. PURPOSE: To characterise the longitudinal retinal ganglion cell layer + inner plexiform layer (GCL + IPL) changes and their association with microvascular changes in type-2 diabetes (T2D) patients with nonproliferative diabetic retinopathy (NPDR). METHODS: This two-year prospective study (CORDIS, NCT03696810) included 122 T2D individuals with NPDR identified as risk phenotypes B and C, which present a more rapid progression. Phenotype C was identified by decreased VD ≥ 2SD in healthy controls, and phenotype B, identified by subclinical macular oedema with only minimal vascular closure. The GCL + IPL thickness, vessel density, perfusion density and area of intercapillary spaces (AIS) were assessed by optical coherence tomography (OCT) and OCT angiography (OCTA). Linear mixed effects models were employed to evaluate the retinal GCL + IPL progression and its associations. RESULTS: Regarding GCL + IPL thickness, T2D individuals presented on average 80.1 ± 7.49 µm, statistically significantly lower than the healthy control group, 82.5 ± 5.71 (p = 0.022), with only phenotype C differing significantly from controls (p = 0.006). GCL + IPL thickness steadily decreased during the two-year period in both risk phenotypes, with an annual decline rate of -0.372 µm/year (p < 0.001). Indeed, phenotype C showed a higher rate of progression (-0.459 µm/year, p < 0.001) when compared to phenotype B (-0.296 µm/year, p = 0.036). Eyes with ETDRS grade 20 showed GCL + IPL thickness values comparable to those of healthy control group (83.3 ± 5.80 and 82.7 ± 5.50 µm, respectively, p = 0.880), whereas there was a progressive decrease in GCL + IPL thickness in ETDRS grades 35 and 43-47 associated with the increase in severity of the retinopathy (-0.276 µm/year, p = 0.004; -0.585 µm/year, p = 0.013, respectively). Furthermore, the study showed statistically significant associations between the progressive thinning of GCL + IPL and the progressive increase in retinal capillary non-perfusion, with particular relevance for AIS (p < 0.001). CONCLUSIONS: Our findings showed that, in eyes with NPDR and at risk for progression, retinal neurodegeneration occurs at different rates in different risk phenotypes, and it is associated with retinal microvascular non-perfusion.

Different Risk Profiles for Progression of Nonproliferative Diabetic Retinopathy: A 2-Year Study.

INTRODUCTION: Characterization of 2-year progression of different risk phenotypes in eyes with mild and moderate nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D). METHODS: A 2-year prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted. Ophthalmological examinations were performed including best corrected visual acuity, color fundus photography and optical coherence tomography (OCT and OCTA). OCT metrics, central retinal thickness and ganglion cell layer + inner plexiform layer (GCL + IPL) thickness were analyzed. OCTA metrics, vessel density (VD), perfusion density (PD) and area of intercapillary spaces (AIS) were obtained from superficial and deep capillary plexus (SCP, DCP). Only phenotype C identified by decreased VD ≥ 2 SD of healthy controls and phenotype B identified by subclinical macular edema with decreased VD < 2 SD of healthy controls were included. RESULTS: One hundred twenty-two eyes from T2D individuals were included in study; 65 eyes (53%) were classified as phenotype B and 57 eyes (47%) as phenotype C. For phenotype B, progression was associated with thinning of the GCL + IPL (ETDRS 35, 1 year p = 0.013, 2 year p < 0.001; ETDRS 43-47, 2 year p = 0.003) and vessel closure involving mainly the DCP for both ETDRS grades (ETDRS 35, 1 year p = 0.025, 2 year p = 0.034; ETDRS 43-47, 1 year p = 0.011). For phenotype C there was also progressive thinning of the GCL + IPL (ETDRS 35, in both years p ≤ 0.001; ETDRS 43-47, 1 year p = 0.002, 2 year p = 0.001), with vessel closure involving mainly SCP (ETDRS 35, 1 year p = 0.012, 2 year p = 0.023 in full-retina), which appeared to stabilize at maximal values in ETDRS grade 43-47 at the end of 2 years. ETDRS severity changes at the end of the 2-year period showed that worsening was associated with phenotype C with changes involving predominantly the SCP (VD, p = 0.005; PD, p = 0.008; AIS, p = 0.005). CONCLUSIONS: Association between ETDRS classification of NPDR severity and identification of different risk phenotypes offers new perspective to predict disease progression in T2D individuals with NPDR.

Characterisation of progression of macular oedema in the initial stages of diabetic retinopathy: a 3-year longitudinal study.

BACKGROUND/OBJECTIVES: To characterise the prevalence and three-year progression of centre-involving diabetic macular oedema (CI-DMO) in minimal to moderate non-proliferative diabetic retinopathy, using optical coherence tomography (OCT) and measurements of retinal fluid using tissue optical reflectivity ratios (OCT-Leakage). METHODS/METHODS: Seventy-four eyes from 74 patients were followed in a 3-year prospective longitudinal observational cohort of type 2 diabetes (T2D) patients using spectral-domain optical coherence tomography (SD-OCT), OCT-Angiography (OCT-A) and OCT-Leakage (OCT-L). Eyes were examined four times with 1-year intervals. Sixteen eyes (17.8%) were excluded from the analysis due to quality control standards. Retinal oedema was measured by central retinal thickness and retinal fluid by using optical reflectivity ratios obtained with the OCT-L algorithm. Vessel density was measured by OCT-A. Thinning of the ganglion cell and inner plexiform layers (GCL + IPL) was examined to identify retinal neurodegenerative changes. Diabetic retinopathy ETDRS classification was performed using the seven-field ETDRS protocol. RESULTS: CI-DMO was identified in the first visit in 9% of eyes in ETDRS groups 10-20, 10% of eyes in ETDRS group 35 and 15% of eyes in ETDRS groups 43-47. The eyes with CI-DMO and subclinical CI-DMO showed a progressive increase in retinal extracellular fluid during the 3-year period of follow-up. The eyes with CI-DMO and increased retinal extracellular fluid accumulation were associated with vision loss. CONCLUSIONS: The prevalence of subclinical CI-DMO and CI-DMO in the initial stages of NPDR occurs independently of severity grading of the retinopathy, showing progressive increase in retinal extracellular fluid and this increase is associated with vision loss (82% 9 out of 11 cases).

Characterization of two-year progression of different phenotypes of nonproliferative diabetic retinopathy.

INTRODUCTION: To characterize the two-year progression of risk phenotypes of nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D) Phenotype C, or ischemic phenotype, identified by decreased skeletonized retinal vessel density (VD), ≥ 2 SD over normal values, and Phenotype B, or edema phenotype, identified by increased retinal thickness, i.e. subclinical macular edema, and no significant decrease in VD. METHODS: A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with 4 visits (baseline, 6-months, one-year and two-year). Ophthalmological examinations included best corrected visual acuity, color fundus photography (CFP) and optical coherence tomography (OCT) and OCT Angiography. Early Treatment Diabetic Retinopathy Study grading was performed at the baseline and last visits based on 7-fields CFP. RESULTS: One hundred and twenty-two eyes from T2D individuals with NPDR fitted in the categories of phenotype B and C and completed the two-years follow-up. Sixty-five (53%) of the eyes were classified as phenotype B and 57 (47%) eyes as phenotype C. Neurodegeneration represented by thinning of the ganglion cell layer and inner plexiform layer was present in both phenotypes and showed significant progression over the two-year period (p<0.001). In phenotype C, significant progression in the two-year period was identified in decreased skeletonized VD (p=0.01), whereas in phenotype B microvascular changes involved preferentially decreases in perfusion density (PD, p=0.012). Phenotype B with changes in VD and PD (flow) and preferential involvement of the deep capillary plexus (p<0.001) is associated with development of center-involved macular edema. DISCUSSION: In the two-year period of follow-up both phenotypes B and C showed progression in retinal neurodegeneration, with changes at the microvascular level characterized by decreases in PD in phenotype B and decreases in VD in phenotype C.

Association between Neurodegeneration and Macular Perfusion in the Progression of Diabetic Retinopathy: A 3-Year Longitudinal Study.

OBJECTIVE AND PURPOSE: The aim of this study was to explore the relation between retinal neurodegenerative changes and vessel closure (VC) in individuals with nonproliferative diabetic retinopathy (NPDR) in a follow-up period of 3 years. DESIGN: This is a 3-year prospective longitudinal study with four annual visits. PARTICIPANTS: This study involved 74 individuals with type 2 diabetes, NPDR, and Early Treatment Diabetic Retinopathy Study grades from 10 to 47, one eye/person. An age-matched healthy control population of 84 eyes was used as control group. METHODS: Participants were annually examined by color fundus photography, spectral domain-optical coherence tomography (SD-OCT) and OCT-angiography (OCTA). VC was assessed by OCTA vessel density maps. SD-OCT segmentations were performed to access central retinal thickness (CRT) and retinal neurodegeneration considered as thinning of the ganglion cell plus inner plexiform layer (GCL + IPL). RESULTS: Type 2 diabetic individuals presented significantly higher CRT (p = 0.001), GCL + IPL thinning (p = 0.042), and decreased vessel density at the superficial capillary plexus (p < 0.001) and full retina (FR) (p = 0.001). When looking at changes occurring over the 3-year period of follow-up (Table 2), there were statistically significant decreases in GCL + IPL thickness (-0.438 µm/year; p = 0.038), foveal avascular zone circularity (-0.009; p = 0.047), and vessel density in superficial capillary plexus (-0.172 mm-1/year; p < 0.001), deep capillary plexus (DCP) (-0.350 mm-1/year; p < 0.001), and FR (-0.182 mm-1/year; p < 0.001). A statistically significant association was identified between GCL + IPL thinning and decrease in DCP vessel density (ß = 0.196 [95% confidence interval: 0.037, 0.355], z = 2.410, p = 0.016), after controlling for age, gender, diabetes duration, hemoglobin A1c level, and CRT. CONCLUSIONS: Retinal neurodegenerative changes show a steady progression during a 3-year period of follow-up in eyes with NPDR and appear to be directly associated with progression in decreased vessel density including vascular closure through preferential involvement of the DCP. Our findings provide evidence that retinal neuropathy is linked with microvascular changes occurring in diabetic patients.

Characterization of One-Year Progression of Risk Phenotypes of Diabetic Retinopathy.

INTRODUCTION: We characterized the progression of different diabetic retinopathy (DR) phenotypes in type 2 diabetes (T2D). METHODS: A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with three visits (baseline, 6 months, and 1 year). Demographic and systemic data included age, sex, diabetes duration, lipid profile, and hemoglobin A1c (HbA1c). Ophthalmological examinations included best-corrected visual acuity (BCVA), color fundus photography (CFP), and optical coherence tomography (OCT and OCTA). Phenotype classification was performed at the 6-month visit based on microaneurysm turnover (MAT, on CFP) and central retinal thickness (CRT, on OCT). Only risk phenotypes B (MAT < 6 and increased CRT) and C (MAT ≥ 6 with or without increased CRT) were included. ETDRS grading was performed at the baseline visit based on seven-field CFP. RESULTS: A total of 133 T2D individuals were included in the study; 81 (60%) eyes were classified as phenotype B and 52 (40%) eyes as phenotype C. Of these, 128 completed the 1-year follow-up. At baseline, eyes with phenotype C showed greater capillary closure (superior capillary plexus, deep capillary plexus, and full retina, p < 0.001) and increased foveal avascular zone (FAZ) area (p < 0.001), indicating more advanced microvascular disease. Neurodegeneration represented by thinning of the ganglion cell layer + inner plexiform layer (GCL + IPL) was present in both phenotypes. When analyzing the 1-year progression of each phenotype, only phenotype C revealed a significant decrease in BCVA (p = 0.02) and enlargement of the FAZ (p = 0.03). A significant progressive decrease in the vessel density of the deep capillary layer and in MAT occurred in both phenotypes, but these changes were particularly relevant in phenotype C and ETDRS grades 43-47. During the 1-year period, both phenotypes B and C showed progression in GCL + IPL thinning (p < 0.001). CONCLUSIONS: In the 1-year period of follow-up, both phenotypes B and C showed progression in retinal neurodegeneration, whereas phenotype C showed more marked disease progression at the microvascular level.

Microaneurysm Turnover in Mild Non-Proliferative Diabetic Retinopathy is Associated with Progression and Development of Vision-Threatening Complications: A 5-Year Longitudinal Study.

BACKGROUND: Analysis of retinal microaneurysm turnover (MAT) has been previously shown to contribute to the identification of eyes at risk of developing clinically significant complications associated with diabetic retinopathy (DR). We propose to further characterize MAT as a predictive biomarker of DR progression and development of vision-threatening complications. METHODS: 212 individuals with type 2 diabetes (T2D; ETDRS grades 20 and 35) were evaluated annually in a 5-year prospective, longitudinal study, by color fundus photography and optical coherence tomography. Endpoints were diabetic macular edema (DME) or proliferative retinopathy (PDR). MAT analysis included determination of MA formation and disappearance rates, automatically assessed using the RetMarkerDR®. Retinopathy severity progression was evaluated using step increases in ETDRS severity levels. RESULTS: Of the 212 individuals, 172 completed the 5-year follow-up study or developed an endpoint (n = 27). MAT calculated at 1 year showed a significant difference between groups of endpoint developments (p = 0.018), particularly MA disappearance rate (p = 0.007). MAT also showed a significant difference between eyes with different ETDRS severity progression in the 5-year period (p = 0.035). CONCLUSIONS: MAT is an indicator of the development of DME and/or PDR as well as of DR severity progression in T2D individuals with mild retinopathy.

Optical Coherence Tomography Angiography Metrics Monitor Severity Progression of Diabetic Retinopathy-3-Year Longitudinal Study.

To examine retinal vessel closure metrics and neurodegenerative changes occurring in the initial stages of nonproliferative diabetic retinopathy (NPDR) and severity progression in a three-year period. Methods: Three-year prospective longitudinal observational cohort of individuals with type 2 diabetes (T2D), one eye per person, using spectral domain-optical coherence tomography (SD-OCT) and OCT-Angiography (OCTA). Eyes were examined four times with one-year intervals. OCTA vessel density maps of the retina were used to quantify vessel closure. Thickness of the ganglion cell + inner plexiform layer (GCL + IPL) was examined to identify retinal neurodegenerative changes. Diabetic retinopathy ETDRS classification was performed using the seven-field ETDRS protocol. Results: A total of 78 eyes/patients, aged 52 to 80 years, with T2D and ETDRS grades from 10 to 47 were followed for 3 years with annual examinations. A progressive increase in retinal vessel closure was observed. Vessel density (VD) showed higher decreases with retinopathy worsening demonstrated by step-changes in ETDRS severity scale (p < 0.001). No clear correlation was observed between neurodegenerative changes and retinopathy progression. Conclusions: Retinal vessel closure in NPDR correlates with DR severity progression. Our findings provide supporting evidence that OCTA metrics of vessel closure may be used as a surrogate for DR severity progression.

A Comparison of Intraocular Lens Power Calculation Formulas in High Myopia.

PURPOSE: To comparatively evaluate the accuracy of newer intraocular lens (IOL) calculation formulas and common third-generation formulas after Wang-Koch adjustment in the prediction of postoperative refraction in highly myopic eyes. METHODS: This was a retrospective study including eyes with high myopia that had uncomplicated cataract surgery with implantation of an AcrySof MA60MA IOL (power range: -5.00 to +5.00 diopters [D]) (Alcon Laboratories, Inc). All patients underwent optical biometry (Carl Zeiss IOLMaster 500 and IOLMaster 700, and Allegro Biograph) and the postoperative spherical equivalent for the implanted IOL was estimated using SRK/T, Holladay 1 (both Wang-Koch adjusted), Haigis, Barrett Universal II, Kane, Ladas, and Hill-RBF v2.0 formulas. Outcomes included the median absolute prediction error (MedAE) and the proportion of eyes within ±0.25, ±0.50, and ±1.00 D of the preoperative prediction. RESULTS: Eighty-two eyes with a mean axial length of 30.89 ± 1.85 mm were included. The MedAE in ascending order was Hill-RBF v2.0 0.31 D, Kane 0.33 D, Barrett 0.36 D, Holladay Iwk 0.37 D, SRK/Twk 0.37 D, Holladay Iwk 0.43 D, HaigisULIB 0.54 D, and Ladas 0.61 D. The formula with the lowest MedAE (Hill-RBF v2.0) yielded a prediction error within ±0.25, ±0.50, and ±1.00 D in 43.1%, 70.6%, and 94.1% of cases, respectively. CONCLUSIONS: Recent formulas such as Barrett Universal II, Kane, and Hill-RBF v2.0 and Wang-Koch adjusted formulas perform well in this subset of patients with high myopia. The Hill-RBF v2.0 formula had the lowest MedAE and highest proportion of eyes within ±0.25, ±0.50, and ±1.00 D of the predicted target. [J Refract Surg. 2021;37(3):207-211.].

Retinal Neurodegeneration in Different Risk Phenotypes of Diabetic Retinal Disease.

Diabetic retinopathy (DR) has been considered a microvascular disease, but it has become evident that neurodegeneration also plays a key role in this complex pathology. Indeed, this complexity is reflected in its progression which occurs at different rates in different type 2 diabetic (T2D) individuals. Based on this concept, our group has identified three DR progression phenotypes that might reflect the interindividual differences: phenotype A, characterized by low microaneurysm turnover (MAT <6), phenotype B, low MAT (<6) and increased central retinal thickness (CRT); and phenotype C, with high MAT (≥6). In this study, we evaluated the progression of DR neurodegeneration, considering ganglion cell+inner plexiform layers (GCL+IPL) thinning, in 170 T2D individuals followed for a period of 5 years, to explore associations with disease progression or risk phenotypes. Ophthalmological examinations were performed at baseline, first 6 months, and annually. GCL+IPL average thickness was evaluated by optical coherence tomography (OCT). Microaneurysm turnover (MAT) was evaluated using the RetMarkerDR. ETDRS level and severity progression were assessed in seven-field color fundus photography. In the overall population there was a significant loss in GCL+IPL (-0.147 µm/year), independently of glycated hemoglobin, age, sex, and duration of diabetes. Interestingly, this progressive thinning in GCL + IPL reached higher values in phenotypes B and C (-0.249 and -0.238 µm/year, respectively), whereas phenotype A remained relatively stable. The presence of neurodegeneration in all phenotypes suggests that it is the retinal vascular response to the early neurodegenerative changes that determines the course of the retinopathy in each individual. Therefore, classification of different DR phenotypes appears to offer relevant clarification of DR disease progression and an opportunity for improved management of each T2D individual with DR, thus playing a valuable role for the implementation of personalized medicine in DR.

Characterization of Disease Progression in the Initial Stages of Retinopathy in Type 2 Diabetes: A 2-Year Longitudinal Study.

Purpose: To characterize 2-year changes occurring in neurodegeneration, edema, and capillary dropout in nonproliferative diabetic retinopathy. Methods: Two-year prospective longitudinal observational cohort of eyes/patients with type 2 diabetes using spectral domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA). Eyes were examined three times with intervals of 1 year. Thickness of the full retina and layer-by-layer measurements were used to identify edema or neurodegeneration. OCTA vessel density maps of the retina were used to identify capillary dropout. Early Treatment Diabetic Retinopathy Study (ETDRS) classification was performed using the seven-field ETDRS protocol. Results: A total of 62 eyes from 62 patients with diabetes were followed for 2 years. After verification for image quality, a total of 44 eyes from 44 patients (30% women) aged 52 to 80 years were retained for data analysis. There were 18 eyes with ETDRS grades 10 to 20, 17 eyes with ETDRS grade 35, and 9 eyes with ETDRS grades 43 to 47. During the 2-year follow-up period, there was a progressive increase in capillary dropout, whereas edema and neurodegeneration remained stable. In multivariate analysis, considering a model adjusted for age, sex, hemoglobin A1C, visual acuity, and diabetes duration, vessel density remained significantly different between Diabetic Retinopathy Severity Scale groups (Wilks' λ = 0.707; P = 0.015) showing association with disease progression. Conclusions: Capillary dropout increased in a period of 2 years in eyes with minimal, mild, and moderate diabetic retinopathy, whereas the presence of edema and neurodegeneration remained stable.

Large-scale opacification of a hydrophilic/hydrophobic intraocular lens.

PURPOSE: To determine the prevalence and risk factors related to the opacification of the LS-502-1 intraocular lens. METHODS: Cross-sectional study including patients submitted to cataract surgery between January 2010 and March 2012, with implantation of the LS-502-1 intraocular lens. Past medical history was registered and a complete ophthalmologic evaluation, that included best-corrected visual acuity, slit-lamp examination and fundoscopy, was performed. Anterior segment photographs were taken whenever intraocular lens opacification was present. RESULTS: One hundred and sixty-nine eyes of 154 patients were included, mean age 78.5 ± 7.9 years. The average follow-up after intraocular lens implantation was 65.6 ± 10.0 months. Intraocular lens opacification was seen in 53.3% (n = 90) and presented as one of four different patterns: peripheral (15.6%, n = 14), central (4.4%, n = 4), diffuse (71.1%, n = 64) and superficial white deposits (8.9%, n = 8). There was no statistically significant association with systemic or ophthalmic conditions. In patients with bilateral implantation, intraocular lens opacification in one eye was significantly related to intraocular lens opacification in the fellow eye. A significant variability in opacification was found across intraocular lens serial numbers: the odds ratio for opacification in intraocular lens with serial number beginning with 200003 was 6.0 when comparing with the remaining lenses. CONCLUSION: The opacification prevalence of the LS-502-1 intraocular lens was 53.3%, which is the highest ever described for any intraocular lens model. Our results suggest that this occurrence is secondary to an interaction between unknown patient variables and problems related to intraocular lens manufacturing and storage procedures.

Characterization of Initial Stages of Diabetic Macular Edema.

PURPOSE: This study is aimed at characterizing the type of retinal edema in the initial stages of retinopathy in type 2 diabetes. METHODS: In this retrospective cross-sectional study, spectral domain optical coherence tomography (OCT) layer by layer analysis of the retina in association with OCT-Leakage, an algorithm to detect sites of low optical reflectivity, were used to examine eyes with minimal, mild, and moderate diabetic retinopathy (DR). RESULTS: A total of 142 eyes from 142 patients (28% women) aged 52-88 years were imaged. Macular edema, either subclinical (SCME) or central-involved macular edema (CIME), was present in 43% of eyes in group 10-20, 41% of eyes in group 35, and 38% of eyes in group 43-47. The inner nuclear layer (INL) was the layer showing higher and most frequent increases in retinal thickness (79%). The edema was predominantly intracellular in group 10-20 (65%) and extracellular in groups 35 (77%) and 43-47 (69%). CONCLUSIONS: Eyes from diabetic patients in the initial stages of DR with different Early Treatment Diabetic Retinopathy Study gradings show similar prevalence of SCME and CIME, independent of the severity of the retinopathy. Retinal edema is located mainly in the INL and appears to be mostly extracellular except in the earliest stages of diabetic retinal disease where intracellular edema predominates.

Microaneurysm turnover is a predictor of diabetic retinopathy progression.

AIM: To analyse retinopathy phenotypes and microaneurysm (MA) turnover in mild non-proliferative diabetic retinopathy (NPDR) as predictors of progression to diabetic central-involved macular oedema (CIMO) in patients with type 2 diabetes mellitus (DM) in two different ethnic populations. METHODS: 205 patients with type 2 DM and mild NPDR were followed in a prospective observational study for 2 years or until development of CIMO, in two centres from different regions of the world. Ophthalmological examinations, including best-corrected visual acuity (BCVA), fundus photography with RetmarkerDR analysis, and optical coherence tomography (OCT), were performed at baseline and 6 12 and 24 months. RESULTS: 158 eyes/patients reached either the study endpoint, CIMO (24) or performed the last study visit (24-month visit) without developing CIMO (134). From the eyes/patients in analysis, 27 eyes (17.1%) progressed to more advanced ETDRS (Early Treatment Diabetic Retinopathy Study) levels: 6 progressed to mild NPDR (level 35), 15 progressed to moderate NPDR (level 43), 5 progressed to moderately severe NPDR (level 47) and 1 progressed to high risk PDR (level 71). Worsening in ETDRS level is associated with phenotype C (p=0.005). From the 130 eyes/patients with a low MA turnover, 18 (13.8%) eyes/patients had an increase in ETDRS level, and from the 19 eyes/patients with a high MA turnover, 9 (47.4%) had an increase in ETDRS level (p<0.001). CONCLUSION: Eyes in the initial stages of diabetic retinopathy show different phenotypes with different risks for progression to CIMO. In phenotype C, MA turnover correlates with ETDRS grading worsening and development of CIMO.

Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial.

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit.

Multimodal Imaging of the Initial Stages of Diabetic Retinopathy: Different Disease Pathways in Different Patients.

The objective of this study was to evaluate the prevalence of different disease pathways (ischemia, neurodegeneration, and edema) in the initial stages of diabetic retinopathy. In this retrospective cross-sectional study, eyes were grouped by diabetic retinopathy severity using the 7-field Early Treatment Diabetic Retinopathy Study (ETDRS) protocol (levels 10-20, 35, and 43-47). Neurodegeneration was identified by thinning of the retinal nerve fiber layer and/or ganglion cell layer. Edema was identified by thickening of the inner nuclear layer, outer plexiform layer, or full retina. Ischemia was identified by metrics of retinal vessel density. Imaging was performed in 142 eyes from 142 patients (28% women) aged 52-88 years. Vessel density (ischemia) was significantly different between the ETDRS groups (P < 0.020). On multivariate regression analysis, it remained significantly different between stages of the disease and showed associations with age (P < 0.001), sex (P = 0.028), and metabolic control (P = 0.034). No significant differences between ETDRS groups were found in retinal thinning (neurodegeneration) or retinal thickness (edema). Eyes with the same ETDRS retinopathy grading from different patients with diabetes showed that the prevalence of different disease pathways varies between patients, even within the same severity group. Ischemia (capillary dropout) is the only disease pathway that shows correlation with retinopathy severity and metabolic control.

Subclinical Macular Edema as a Predictor of Progression to Central-Involved Macular Edema in Type 2 Diabetes.

PURPOSE: The aim of this study was to examine the relationship between subclinical diabetic macular edema (SCME) and the development of central-involved macular edema (CIME) in patients with diabetes mellitus type-2 and mild nonproliferative diabetic retinopathy (NPDR), from 2 populations of different ethnicities. METHODS: Two hundred and five patients with diabetes mellitus type-2 and mild NPDR with no prior laser or intravitreal treatment were followed for 2 years or until the development of CIME. Ophthalmological examinations, including BCVA, fundus photography with RetmarkerDR analysis, and optical coherence tomography were performed at baseline and months 6, 12, and 24. RESULTS: One hundred and fifty eight eyes/patients reached either the study endpoint, CIME (n = 24), or performed the 24-month visit without developing CIME (n = 134). Fifty eyes/patients had SCME at baseline (31.6%). Of these 50 eyes, 16 (32.0%) developed CIME, whereas of the 108 eyes with normal retinal thickness (RT) at baseline, only 8 (7.4%) developed CIME (p < 0.001). Patients with increased RT in the central subfield at baseline showed a 12-fold risk of progression to CIME compared with patients without SCME. CONCLUSIONS: In patients with mild NPDR, the presence of SCME is a good predictor of progression to CIME.