Early Treatment Diabetic Retinopathy Study Research Articles

Hyperreflective foci distribution in eyes with dry age-related macular degeneration with subretinal drusenoid deposits.

To investigate the distribution of hyperreflective foci (HRF) in eyes with dry age-related macular degeneration (AMD). We retrospectively reviewed optical coherence tomography (OCT) images of 58 dry AMD eyes presenting HRF. The distribution of HRF according to the early treatment diabetic retinopathy study area was analyzed according to the presence of subretinal drusenoid deposits (SDDs). We classified 32 eyes and 26 eyes into the dry AMD with SDD group (SDD group) and dry AMD without SDD group (non-SDD group), respectively. The non-SDD group had higher prevalence and density of HRF at the fovea (65.4% and 1.71 ± 1.48) than the SDD group (37.5% and 0.48 ± 0.63, P = 0.035 and P < 0.001, respectively). However, the prevalence and density of HRF in the outer circle area of the SDD group (81.3% and 0.11 ± 0.09) were greater than those of the non-SDD group (53.8% and 0.05 ± 0.06, p = 0.025 and p = 0.004, respectively). The SDD group showed higher prevalence and mean densities of HRF in the superior and temporal area than in the non-SDD group (all, p < 0.05). HRF distributions in dry AMD varied according to the presence of SDDs. This might support that the degenerative features may be different between dry AMD eyes with and without SDDs.

Retinal microvascular and microstructural alterations in the diagnosis of dermatomyositis: a new approach.

To study the relationship between fundus alterations, including retinal thickness and microvascular changes, and dermatomyositis (DM) using optical coherence tomography angiography (OCTA). A total of 16 patients with DM (32 eyes) and 16 healthy controls (HCs; 32 eyes) participated in this study. Based on the Early Treatment Diabetic Retinopathy Study subzones, OCTA fundus data were divided into different layers and regions for comparison. The full retinal thickness (RT) in the inner nasal (IN), outer nasal (ON), inner inferior (II), and outer inferior (OI) regions of patients with DM was significantly lower than that of HCs (P < 0.001). The inner layer RT was also significantly lower in the IN, ON, II, and OI regions in patients with DM (P < 0.001). The outer layer RT was lower only in the II region in patients with DM compared to HCs (P < 0.001). The full RT of the II region was more sensitive to the pathological changes of disease since its ROC curve had an AUC of 0.9028, 95% CI: 0.8159-0.9898. Meanwhile, the superficial vessel density (SVD) of patients with DM was significantly lower in the IN, ON, II, and OI regions compared to HCs (P < 0.001). The AUC for region II was 0.9634 (95% CI: 0.9034-1.0), which indicated good diagnostic sensitivity. Optical coherence tomography angiography can be used to evaluate relevant ocular lesions and monitor disease progression in patients with DM and interstitial lung disease.

SCORE2 Report 24: Nonlinear Relationship of Retinal Thickness and Visual Acuity in Central Retinal and Hemiretinal Vein Occlusion

To investigate whether a nonlinear association between central subfield thickness (CST) on spectral-domain OCT and concurrent visual acuity letter score (VALS) exists in eyes treated initially with aflibercept or bevacizumab for macular edema associated with central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). Long-term follow-up after a randomized clinical trial from 64 centers in the United States. Participants were followed up to 60 months and treated at investigator discretion after completing the 12-month treatment protocol. Two-segment linear regression models were compared with simple linear regression models of VALS on CST. Pearson correlation coefficients were calculated to assess strength of CST and VALS associations. Central subfield thickness was measured by OCT and VALS by the electronic Early Treatment Diabetic Retinopathy Study methodology. Estimated inflection points, reflecting turning points at which the CST and VALS association changes from positive to negative, calculated at 7 postbaseline visits, range from 217 to 256 μm. A strongly positive correlation exists to the left of each estimated inflection point, ranging from 0.29 (P < 0.01 at month 60) to 0.50 (P < 0.01 at month 12), and a strongly negative correlation exists to the right of each estimated inflection point, ranging from -0.43 (P < 0.01 at month 1) to -0.74 (P < 0.01 at month 24). Randomization statistical tests showed that 2-segment models are favored over 1-segment models for all postbaseline months (P < 0.001 for all tests performed). The relationship between CST and VALS in eyes with CRVO or HRVO after treatment with anti-vascular endothelial growth factor (VEGF) therapy is not simply linear. The usually modest correlations between OCT-measured CST and visual acuity belie strong left and right correlations present in 2-segment models. Post-treatment CST close to the estimated inflection points showed the best expected VALS. The SCORE2 participants with a post-treatment CST after treatment close to the estimated inflection points of 217 to 256 μm showed the best VALS. In patients treated with anti-VEGF for macular edema associated with CRVO or HRVO, a thinner retina is not always associated with better VALS. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A real-world study for timely assessing the diabetic macular edema refractory to intravitreal anti-VEGF treatment.

Early Identifying and characterizing patients with diabetic macular edema (DME) is essential for individualized treatment and outcome optimization. This study aimed to timely investigate optical coherence tomography (OCT) biomarkers of DME refractory to intravitreal anti-vascular endothelial growth factor (VEGF) therapy. We retrospective reviewed 72 eyes from 44 treatment-naïve patients who were treated with intravitreal anti-VEGF for DME. OCT scans prior to anti-VEGF were evaluated for serous retinal detachment (SRD), size of outer nuclear layer cystoid changes, diffuse retinal thickening, integrity of the inner segment-outer segment (IS-OS) junction, quantity and location of hyperreflective foci, vitreomacular interface abnormalities, and epiretinal membrane (ERM). The Baseline best-corrected visual acuity (BCVA) and central macular thickness was recorded at baseline and 4 months after treatment with anti-VEGF. The main outcome measure was the correlation between spectral-domain OCT measurements and BCVA response at baseline and after anti-VEGF treatment (mean change from baseline; ≥ 10 Early Treatment Diabetic Retinopathy Study letters in BCVA). Partially continuous IS-OS layers (partially vs. completely continuous: β, -0.138; Wald chi-square, 16.392; P<0.001) was predictor of better response to anti-VEGF treatment. In contrast, ERM (present vs. absent ERM: β, 0.215; Wald chi-square, 5.921; P=0.015) and vitreomacular traction (vitreomacular traction vs. posterior vitreous detachment: β=0.259; Wald chi-square=5.938; P=0.015) were the predictors of poor response. The improvement of BCVA trended toward the OCT predictive value of central macular thickness reduction; however, this was not significant. Partially continuous IS-OS layers is predictive of better response to anti-VEGF therapy in DME. Meanwhile, ERM is a significant predictor of poor response.

Retinal vascular structure independently predicts the initial treatment response in neovascular age-related macular degeneration.

Prediction of the early treatment response is important in neovascular age-related macular degeneration (nAMD). Hence, we aimed to test if non-invasive measurements of the retinal vascular structure were able to predict a successful outcome of initial intravitreal treatment. In 58 eyes of 58 patients with treatment-naïve nAMD, advanced markers of retinal vascular structure were measured by Singapore I Vessel Assessment prior to initial intravitreal treatment with three monthly injections of aflibercept with subsequently categorization of patients as full treatment responders (FTR) or non/partial treatment responders (N/PR), with the former defined as loosing fewer than five Early Treatment Diabetic Retinopathy Study letters and having no residual intra- or subretinal fluid or macular haemorrhage. Of 54 eyes attending follow-up, 44.4% were categorized as FTR. Patients with FTR were older (81.5 vs. 77 years, p = 0.04), and prior to treatment those eyes had a lower retinal arteriolar fractal dimension (Fd) (1.21 vs. 1.24 units, p = 0.02) and venular length-diameter ratio (LDR) (7.3 vs. 15.9 units, p = 0.006), but did not differ with respect to other retinal vascular parameters. In multiple logistic regression models, a lower chance of FTR was independently predicted by a higher retinal venular LDR (odds ratio [OR] 0.91, 95% CI 0.82-0.99, p = 0.03, for each 1 unit increment) and marginally by a higher retinal arteriolar Fd (OR 0.83, 95% CI 0.68-1.00, p = 0.05, for each 0.01 unit increment). Retinal venular LDR independently predicted the initial treatment response in nAMD. If confirmed by long-term, prospective studies, this might help to guide treatment.

Peripheral retinal vessel whitening in patients with diabetes mellitus

This study aimed to identify retinal vessel whitening outside the standard Early Treatment Diabetic Retinopathy Study (ETDRS) fields and to correlate the findings with vision and severity of diabetic retinopathy. Patients with diabetes mellitus who were seen in the retinal clinic to assess diabetic retinopathy status were included. Retinal vessel whitening was identified using ultra-widefield imaging. Four hundred and forty-five eyes of 260 patients were included. Thirty-five eyes in 24 patients (7.9%) were noted to have peripheral retinal vessel whitening. Thirty-one eyes with peripheral retinal vessel whitening did not have vessel whitening within the standard 7 ETDRS fields (p < 0.001). The proportion of whitening increased as DR severity increased, from 4.0% for patients with no DR (OR 0.249) to 33.3% for those with severe NPDR and PDR (OR 6.430 and 7.232, respectively). In addition, patients with peripheral retinal vessel whitening had worse visual acuity (logMAR = 0.34) compared to those without (logMAR = 0.15) (p < 0.001). In conclusion, we found an association between peripheral retinal vessel whitening in diabetic patients which correlated with diabetic retinopathy severity. Additionally, we found an association between vessel whitening and reduced vision, suggesting that vessel whitening identified using ultra-widefield imaging may be a prognostic indicator of vision in diabetic retinopathy.

Visual function in adults born preterm with very low birth weight-A two-country birth cohort study.

The purpose of the study was to investigate visual function and vision-related general health in adults that were born preterm with very low birth weight (VLBW: birth weight < 1500 g) in their 30s-40s. We recruited 137 adults born preterm with VLBW and 158 term-born controls aged 31-43 years from two birth cohorts: the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight in a Lifetime Perspective study (Norway). We used neonatal data and measured refraction, best-corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, contrast sensitivity, visual fields, intraocular pressure (IOP), self-reported vision-targeted health status with the National Eye Institute Visual Function Questionnaire-25. VLBW adults had a lower BCVA ETDRS score than controls: mean (SD) better eye 86.7 (13.4) versus 90.2 (4.4), p = 0.02; mean (SD) worse eye 82.3 (14.9) versus 87.6 (4.6), p = 0.003. VLBW adults also had lower contrast sensitivity thresholds in several spatial frequencies and scored lower than controls in eight out of the 12 subscales of self-reported vision-targeted health status. Refraction, visual fields and IOP were similar between groups. Two VLBW participants were blind. None had been treated for retinopathy of prematurity. We suggest that lower visual function and vision-related health represent life-long consequences of prematurity and VLBW in the studied 31- to 43-year-old cohort. The underlying mechanisms remain to be determined.

Decreased Central Macular Choriocapillaris Perfusion Correlates With Increased Low Luminance Visual Acuity Deficits

Correlations between low luminance visual acuity deficits (LLVADs) and central choriocapillaris perfusion deficits were investigated to help explain how increases in LLVAD scores at baseline predict annual growth rates of geographic atrophy (GA). Prospective cross-sectional study. Photopic luminance best-corrected visual acuity (PL-BCVA) and low luminance BCVA (LL-BCVA) were measured using the Early Treatment Diabetic Retinopathy Study chart. LL-BCVA was measured using a 2.0-log unit neutral density filter. LLVADs were calculated as the difference between PL-BCVA and LL-BCVA. Within a fovea-centered 1-mm circle, the percentage of choriocapillaris flow deficits (CC FD%), drusen volume, optical attenuation coefficient (OAC) elevation volume, and outer retinal layer (ORL) thickness were assessed. In all 90 eyes (30 normal eyes; 31 drusen-only eyes; 29 non-foveal GA eyes), significant correlations were found between the central CC FD% and PL-BCVA (r=-0.393, P < .001), LL-BCVA (r=-0.534, P < .001), and the LLVAD (r=0.439, P < .001). Central cube root (cubrt) drusen volume, cubrt OAC elevation volume, and ORL thickness were correlated with PL-BCVA, LL-BCVA, and LLVADs (all P < .05). Stepwise regression models showed that central cubrt OAC elevation volume and ORL thickness were associated with PL-BCVA (R2=0.24, P < .05); central CC FD%, cubrt OAC elevation volume, and ORL thickness were associated with LL-BCVA (R2=0.44, P < .01); and central CC FD% and ORL thickness were associated with LLVAD (R2=0.24, P < .01). The significant correlations between central CC FD% and LLVAD support the hypothesis that the ability of LLVAD to predict the growth of GA is mediated through a decrease in macular choriocapillaris perfusion.

Comparison of quantitative assessment and efficiency of diabetic retinopathy diagnosis using ETDRS seven-field imaging and two ultra-widefield imaging.

This study compared the efficiency of diabetic retinopathy (DR) diagnosis and differences in the relative visible retinal area among the Early Treatment Diabetic Retinopathy Study (ETDRS) seven-field, ultra-widefield (UWF)-Optos, and UWF-Clarus fundus imaging methods. This was a prospective and clinic-based comparative study. All patients underwent three fundus examinations, and all images were graded using the ETDRS severity scale. We compared and analysed the agreement of DR severity and the relative visible retinal area among the three fundus examination methods, and the number and type of lesions outside the ETDRS seven-field (peripheral lesions) between the two UWF imaging methods. A total of 202 patients (386 eyes) were included. Weighted kappa for the agreement between ETDRS seven-field and blinded Optos images was 0.485; between ETDRS seven-field and blinded Clarus images, 0.924; and between blinded Optos and Clarus images, 0.461. Blinded Clarus showed excellent performance when a ETDRS scale was used for grading the images. The relative visible retinal area for ETDRS seven-field images was 195 ± 28 disc area (DA); single Optos images, 371 ± 69 DA; single Clarus images, 261 ± 65 DA; two-montage Clarus images, 462 ± 112 DA; and four-montage Clarus images, 598 ± 139 DA. The relative visible retinal area was statistically significant between any two of the imaging systems used. In total, 2015 and 4200 peripheral lesions were detected in single Optos and Clarus images, respectively (P < 0.001). These peripheral lesions on two UWF images suggested a more severe DR level in approximately 10% and 12% of eyes, respectively. UWF-Clarus fundus imaging offers a suitable assessment approach for DR severity; it could improve DR diagnosis and has the potential to replace ETDRS seven-field imaging after additional clinical trials.

The association between diabetic retinopathy, cognitive impairment, and quality of life – a cross sectional study

BackgroundDiabetic retinopathy (DR), a microangiopathy caused by Type 2 Diabetes Mellitus (T2DM), is associated with significant visual disability leading to suboptimal quality of life. Retinal microvasculature changes can reflect similar changes in the grey matter and blood-brain barrier. Microvascular changes in the brain are associated with cognitive dysfunction. The present study aimed to find the association between Diabetic Retinopathy (DR) and Cognitive Impairment (CI) and its relationship with Quality of Life (QoL). MethodologyA cross-sectional observational study was conducted in a tertiary care hospital among patients (aged 18 years and above) with pre-existing T2DM as per Standards of Care in Diabetes-2023 criteria. Patients with visual acuity less than 3/60, or education below 6th grade, or with comorbid mental or neurocognitive disorders illness were excluded from the study. DR grading was done using the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria. Cognitive functions and quality of life were measured using Montreal cognitive assessment (MoCA) and World Health Organization – Quality of Life scale – brief version (WHO-QOL BREF). The primary outcome measures (cognitive impairment and quality of life) were compared between patients with DR (DR+) and patients without DR (DR-). A P < 0.05 was considered statistically significant. ResultsDiabetic retinopathy was diagnosed in 48.5% (83 out of 171) of the sample. The DR+ group were predominantly male, significantly older, had comorbid immature cataract and hypertension than the DR- group. Also, the DR+ group had significantly reduced scores in all domains of MoCA and QoL. among patients with DR, those with severe and moderate NPDR had more cognitive impairment than mild NPDR. Age and duration of diabetes did not correlate with MoCA and QoL scores. ConclusionThe presence of diabetic retinopathy is associated with cognitive impairment and reduced quality of life in this study population. The association is independent of the age of patient and the duration of diabetes mellitus.

Intravitreal bevacizumab plus propranolol for neovascular age-related macular degeneration (the BEVALOL study): a phase I clinical trial

BackgroundGiven the persistently large public health impact of neovascular age-related macular degeneration (nARMD) despite many years of anti-VEGF therapy as the first-line treatment and the demonstrated ability of b-blockers to reduce neovascularization, a synergistic effect between an anti-VEGF agent and an intravitreal beta-blocker is important to investigate in the quest for therapeutic alternatives that maximize efficacy and/or reduce costs. The main purpose of this study is to investigate the safety of a 0.1 ml intravitreal injection of a combination of bevacizumab (1.25 mg/0.05 ml) and propranolol (50 g/0.05 ml) to treat nARMD.MethodsProspective phase I clinical trial that included patients with nARMD. Comprehensive ophthalmic evaluation was performed at baseline and included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), biomicroscopy of the anterior and posterior segments, binocular indirect ophthalmoscopy, color fundus photography, spectral domain optical coherence tomography (OCT), OCT angiography (OCT-A), fluorescein angiography (Spectralis, Heidelberg), and full-field electroretinography (ERG). All eyes were treated with a 0.1 ml intravitreal injection of a combination of bevacizumab (1.25 mg/0.05 ml) and propranolol (50 g/0.05 ml) within 1 week of baseline evaluation. The patients were reexamined at weeks 4, 8 and 12, and clinical evaluation and SD-OCT were performed at all follow-up visits. Additional injections of combination bevacizumab (1.25 mg/0.05 ml) and propranolol (50 g/0.05 ml) were administered at weeks 4 and 8. At the final study evaluation (week 12), color fundus photography, OCT-A, fluorescein angiography, and full-field ERG were repeated.ResultsEleven patients (11 eyes) completed all study visits of the 12 week study. Full field ERG b-waves did not show significant (p < 0.05) changes at week 12 compared to baseline. During the 12 week follow-up period, none of the study eyes developed intraocular inflammation, endophthalmitis or intraocular pressure elevation more than 4 mmHg over baseline. Mean ± SE BCVA (logMAR) was 0.79 ± 0.09 at baseline and was significantly (p < 0.05) improved to 0.61 ± 0.10 at week 4; 0.53 ± 0.10 at week 8; and 0.51 ± 0.09 at week 12. Mean ± SE central subfield thickness (CST) (μm) was 462 ± 45 at baseline and was significantly (p < 0.05) lower at 4, 8 and 12 weeks (385 ± 37; 356 ± 29 and 341 ± 24, respectively).ConclusionsIn this 12 week trial of a combination of intravitreal bevacizumab and propranolol for treatment of nARMD, no adverse events or signals of ocular toxicity were observed. Further studies using this combination therapy are warranted.Trial Registration Project registered in Plataforma Brasil with CAAE number 28108920.0.0000.5440 and approved in ethics committee of Clinics Hospital of Ribeirao Preto Medicine School of São Paulo University—Ribeirão Preto, São Paulo, Brazil (appreciation number 3.999.989 gave the approval).

Vision-related quality of life is selectively affected by comorbidities in patients with geographic atrophy

BackgroundThe atrophic late stage of age-related macular degeneration (AMD) is termed geographic atrophy (GA), and affects visual acuity (VA) as well as quality of life (QoL). Previous studies have found that best-corrected VA (BCVA), the standard vision assessment often underrepresents functional deficits. Therefore, the purpose of this study was to evaluate the correlation between atrophic lesion size, VA and QoL measured with the National Eye Institute Visual Function Questionnaire (VFQ-39) in a Danish population. Moreover, we wanted to evaluate the correlation between comorbidities, behavioural factors, and QoL.MethodsThis was prospective clinical study of 51 patients with GA in one or both eyes, of these 45 patients had bilateral GA. Patients were consecutively included between April 2021 and February 2022. All patients filled in the VFQ-39 questionnaire except the subscales “ocular pain” and “peripheral vision.” Lesion size was measured from fundus autoflourescense images, and BCVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol.ResultsWe found an overall low score in each VFQ-39 subscale scores reflected by GA. Lesion size and VA were both significantly associated with all VFQ-39 subscale scores except for “general health.” VA showed a larger effect on QoL than lesion size. Chronic obstructive pulmonary disease (COPD) was associated with a lower score in the subscale score “general health” but none of the other subscale scores were affected. Cardiovascular disease (CVD) was associated with a lower BCVA as well as in QoL reflected in the subscale scores “poor general vision,” “near activities,” and “dependency” of VFQ-39.ConclusionBoth atrophic lesion size and visual acuity affects QoL in Danish patients with GA, who reports an overall poor QoL. CVD seems to have a negative effect on disease, as well as in VFQ-39 in several subscales, whereas COPD did not affect disease severity or vision-related subscales in VFQ-39.

Ten-Year Incidence of Fibrosis and Risk Factors for Its Development in Neovascular Age-Related Macular Degeneration

To report the incidence and risk factors for fibrosis at 10 years in a large cohort of persons with neovascular age-related macular degeneration (nAMD). Retrospective, multicenter, cohort study. We included 225 naive nAMD eyes that underwent intravitreal anti-vascular endothelial growth factor treatment over 10 years of follow-up at two Italian referral centers. Demographic and clinical data were reviewed at baseline and on an annual basis. Onset of fibrosis was defined by clinically assessing photographs, fundus descriptions, or fluorescein angiograms. Optical coherence tomography (OCT) scans of fibrosis were inspected by an external reading center and graded as subretinal pigment epithelium (RPE), mixed, or subretinal. The mean age at baseline was of 72.1 ± 6.9 years. The incidence rate of fibrosis was estimated to be 8.9 per 100 person-years, with a cumulative incidence of 62.7% at 10 years. Fibrotic lesions were sub-RPE in 46.1%, mixed in 29.8%, and subretinal in 22.7%. Independent factors associated with fibrosis included the following: larger central subfield thickness variation (P < .001), submacular hemorrhages (P=.008), higher number of injections (P=.01), and worse baseline visual acuity (VA) (P=.03). Type 2 macular neovascularization was significantly associated with mixed and subretinal fibrosis. VA significantly declined over 10 years (-16.4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters), particularly in eyes with mixed and subretinal fibrosis (P < .001). We identified a 62.7% cumulative incidence of fibrosis in a large nAMD cohort at 10 years. Fibrosis was more common with frequent reactivations and lower baseline VA; its onset had a significant impact on final VA. This supports the hypothesis that nAMD patients should be promptly treated with proactive regimens.

Direct Macular Hole Manipulation Results in High Success Rate in Secondary Macular Hole Repair.

To investigate closure rates and functional outcomes of surgery for refractory and recurrent macular holes (MH) in a real-world setting. Retrospective review of secondary MH surgeries. A total of 72 eyes from 72 patients were included. Eyes had a mean of 1.51 surgeries before inclusion into the study with a mean MH size of 762 µm and a mean baseline logMAR BCVA of 1.11(∼20/260 Snellen). Closure rates were 89.3 % for tissue transplantation, 77.3 % for ILM flaps, 92.9 % for MH manipulation, and 12.5 % for repeat ILM peeling (p<0.05). BCVA changes in logMAR from baseline to postoperative month 6 were +0.29 for ILM peeling alone (15 ETDRS letters worse), -0.39 for macular hole manipulation (20 ETDRS letters improved), -0.23 for tissue transplantation (13 ETDRS letters improved), and -0.2 for ILM flaps (10 ETDRS letters improved; p<0.05). Secondary MH closure is possible using various surgical techniques with acceptable anatomical closure rates. Repeat ILM peeling is associated with the lowest closure rates and poorest functional results. To distinguish between techniques would require a large sample size of about 750 eyes.

Associations and Prognostic Significance of Fluctuations in Diabetic Retinopathy Severity in Eyes Treated for Diabetic Macular Edema

Introduction: The aim of our study was to investigate factors associated with diabetic retinopathy (DR) severity fluctuations in patients undergoing intravitreal injections for diabetic macular edema and to explore risk factors for proliferative DR (PDR). Methods: We graded ultra-widefield fundus photography imaging at each visit using the Early Treatment Diabetic Retinopathy Study Severity Scale (DRSS). We calculated the deviation from the mode (DM) of DRSS values as a proxy of DR severity fluctuations, and we analyzed its clinical associations with linear models. We computed risk factors for PDR with Cox hazard models. We included the DRSS area-under-the-curve (AUC) of DRSS scores as a covariate in all analyses. Results: We included 111 eyes with a median follow-up of 44 months. Higher DRSS-AUC values (β = +0.03 DRSS DM for unitary DRSS/month increase, p = 0.01) and a higher number of anti-VEGF injections (β = +0.07 DRSS DM for injection, p = 0.045) were associated with wider DR severity fluctuations. Higher DRSS-AUC values (HR = 1.45 for unitary DRSS/month increase, p = 0.001) and wider DR severity fluctuations (HR = 22.35 4th quartile vs. 1st–3rd quartile of DRSS DM, p = 0.01) were risk factors for PDR. Conclusion: Patients with larger DR variability in response to intravitreal injections may be at higher risk of DR progression. We advocate attentive follow-up in these patients to recognize PDR early.

Quadrant Asymmetry in Optical Coherence Tomography Angiography Metrics in Ischemic Versus Non-Ischemic Central Retinal Vein Occlusion Eyes.

To determine whether quadrant asymmetry (QA) of optical coherence tomography angiography (OCTA) metrics differs between non-ischemic versus ischemic central retinal vein occlusion (CRVO). Fifty-eight eyes (21 non-ischemic, 10 ischemic CRVO, and 27 contralateral control eyes) underwent 3 × 3 mm spectral-domain OCTA scans with quantification of the superficial retinal layer vessel length density (VLD) and perfusion density (PD). QA, defined as the maximum-minus-minimum value among four parafoveal Early Treatment Diabetic Retinopathy Study (ETDRS) quadrants, was compared by linear regression including fixed effects for each eye. Mean age was 73.6 ± 11.4 (range 39-88), 73.8 ± 12.4 (range 39-91) and 77.2 ± 9.83, (range 60-88); and QA was 3.46 ± 1.76, 3.14 ± 1.57, and 4.88 ± 2.42 for VLD and 0.072 ± 0.038, 0.062 ± 0.036, and 0.11 ± 0.056 for PD for control, non-ischemic, and ischemic, respectively. QA was significantly higher in ischemic (0.109 ± 0.056) than non-ischemic CRVO eyes (0.062 ± 0.036; P = 0.02) and control eyes for PD (0.072 ± 0.038; P = 0.03). QA was also greater in ischemic (4.875 ± 2.418) than non-ischemic CRVO (3.141 ± 1.572) for VLD (P = 0.04). In terms of identifying which particular quadrant is most affected by ischemia, multivariate regression analysis comparing intra-quadrant effect on the presence of ischemia versus non-ischemia showed no quadrant was significantly affected (P > 0.05 for all quadrants). Ischemic CRVO increases intraeye QA of OCTA metrics when compared to non-ischemic CRVO and control eyes. No specific ETDRS quadrant appears to be more affected. This work uses an intraeye method to delineate between ischemic and non-ischemic CRVO by OCTA imaging, overcoming inter-eye variables encountered in clinical care.

ASSOCIATION OF OCULAR PERFUSION PRESSURE AND CEREBROSPINAL FLUID PRESSURE WITH CHANGES IN DIABETIC RETINOPATHY.

To investigate the association between mean ocular perfusion pressure (MOPP), estimated cerebrospinal fluid pressure (CSFP), and changes in diabetic retinopathy (DR) in a Northeastern Chinese population with Type 2 diabetes. A total of 1,322 subjects from the Fushun Diabetic Retinopathy Cohort Study were enrolled. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and intraocular pressure (IOP) were recorded. MOPP was calculated by the following formula: MOPP = 2/3 [DBP + 1/3 (SBP - DBP)] - IOP, and CSFP was estimated according to the following formula: CSFP = 0.44 × body mass index + 0.16 × DBP - 0.18 × age - 1.91. New development, progression, and regression of DR were graded based on fundus photographs at baseline and during follow-up examinations with a mean interval of 21.2 months using the modified Early Treatment Diabetic Retinopathy Study criteria. Increasing MOPP was associated with the incidence of DR in the multivariate model (per 1-mmHg increase: relative risk, 1.06; 95% confidence interval, 1.02-1.10; P = 0.007) and showed a borderline negative association with DR regression (per 1-mmHg increase: relative risk, 0.98; 95% confidence interval, 0.97-1.00; P = 0.053). However, MOPP was not associated with progression of DR. Cerebrospinal fluid pressure was not associated with new development, progression, or regression of DR. The MOPP, but not the CSFP, was found to influence the development, but not the progression of DR in this Northeastern Chinese cohort.

Design and Validation of a Novel Smartphone-Based Visual Acuity Test: The K-VA Test.

Visual acuity (VA) testing is a critical screening examination for the assessment of visual function. This study describes the development and validation of a smartphone-based VA test: the K-VA test. A total of 171 patients with various ocular diseases were examined in our outpatient unit at Aristotle University of Thessaloniki, School of Medicine in Greece. Participants underwent VA examination using the standard Early Treatment Diabetic Retinopathy Study (ETDRS)charts and the K-VA smartphone-based test. The K-VA test was performed by participants themselves. The Bland-Altman method was employed to assess the agreement between the ETDRS charts and the new test for the examination of VA at 1m and 40cm. Test-retest reliability was also calculated. A questionnaire regarding the participants' feedback on the K-VA test was completed. No significant bias wasobserved between the gold standard ETDRS charts and the K-VA test measurements. The mean difference (95% limits of agreement, LoA) between the K-VA test at 1m and the ETDRS chart at 4m was -0.006 (95% LoA -0.129 to 0.117) logarithm of the minimal angle of resolution (logMAR). The agreement of the K-VA test at 40cm with thenear ETDRS chart was also high with a mean difference of -0.007 (95% LoA -0.105 to 0.090) logMAR. Test-retest reliability was found to be high with a mean difference of 0.003 (95% LoA -0.045 to 0.033) logMAR and 0.005 (95% LoA -0.065 to 0.076) logMAR for theK-VA testat 1m and 40cm, respectively. A total of 97 participants answered the questionnaire and 71 (73.2%) stated that the test was easy to very easy to use for self-performance. The study demonstrated that the K-VA application performed well compared with the ETDRS charts and provides reliable and repeatable measurements of VA across a wide range of VA.

Comparison of Conventional and Femtosecond Laser-Assisted Cataract Surgery Regarding Macula Behavior and Thickness.

Background: The aim of the study was to compare macular thickness behavior and clinical outcomes after femtosecond laser-assisted cataract surgery (FLACS) versus phacoemulsification conventional surgery (PCS). Methods: Macular Optical Coherence Tomography OCT was analyzed in 42 patients preoperatively, 1 day, 12 days, 4 weeks and 6 weeks postoperatively according to the 9-field Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Clinical findings were collected in both the FLACS group and the PCS group. Results: There was no significant difference in macular thickness between the FLACS and PCS groups (p > 0.05). However, from postoperative day 12 onwards, there was a significant increase in macular thickness observed in both groups (p < 0.001). In the FLACS group, a significant increase in visual acuity was observed on the first postoperative day, as compared to the PCS group (p = 0.006). Conclusions: The use of a low-energy high-frequency femtosecond laser has potentially no effect on postoperative macular thickness. In the FLACS group, visual rehabilitation was significantly faster as compared to the PCS group. No complications occurred intraoperatively in either group.

Macular Anatomy Differs in Dyslexic Subjects.

The macula, as the central part of the retina, plays an important role in the reading process. However, its morphology has not been previously studied in the context of dyslexia. In this research, we compared the thickness of the fovea, parafovea and perifovea between dyslexic subjects and normal controls, in 11 retinal segmentations obtained by optical coherence tomography (OCT). With this aim, we considered the nine sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and also summarized data from sectors into inner ring subfield (parafovea) and outer ring subfield (perifovea). The thickness in all the four parafoveal sectors was significantly thicker in the complete retina, inner retina and middle retina of both eyes in the dyslexic group, as well as other macular sectors (fovea and perifovea) in the inner nuclear layer (INL), inner plexiform layer (IPL), IPL + INL and outer plexiform layer + outer nuclear layer (OPL + ONL). Additionally, the inner ring subfield (parafovea), but not the outer ring subfield (perifovea), was thicker in the complete retina, inner retina, middle retina (INL + OPL + ONL), OPL + ONL, IPL + INL and INL in the dyslexic group for both eyes. In contrast, no differences were found between the groups in any of the sectors or subfields of the outer retina, retinal nerve fiber layer, ganglion cell layer or ganglion cell complex in any eye. Thus, we conclude from this exploratory research that the macular morphology differs between dyslexic and normal control subjects, as measured by OCT, especially in the parafovea at middle retinal segmentations.