Enhancing Diabetic Macular Edema Treatment Outcomes: Exploring the ESASO Classification and Structural OCT Biomarkers.

INTRODUCTION: This study assessed the European School of Advanced Studies in Ophthalmology (ESASO) classification's prognostic value for diabetic macular edema (DME) in predicting intravitreal therapy outcomes. METHODS: In this retrospective, multicenter study, patients aged > 50 years with type 1 or 2 diabetes and DME received intravitreal antivascular endothelial growth factor (anti-VEGF) agents (ranibizumab, bevacizumab, and aflibercept) or steroids (dexamethasone). The primary outcome was visual acuity (VA) change post-treatment, termed as functional response, measured 4-6 weeks post-third anti-VEGF or 12-16 weeks post-steroid injection, stratified by initial DME stage. RESULTS: Of the 560 eyes studied (62% male, mean age 66.7 years), 31% were classified as stage 1 (early), 50% stage 2 (advanced), 17% stage 3 (severe), and 2% stage 4 (atrophic). Visual acuity (VA; decimal) improved by 0.12-0.15 decimals in stages 1-2 but only 0.03 decimal in stage 3 (all p < 0.0001) and 0.01 in stage 4 (p = 0.38). Even in eyes with low baseline VA ≤ 0.3, improvements were significant only in stages 1 and 2 (0.12 and 0.17 decimals, respectively). Central subfield thickness (CST) improvement was greatest in stage 3 (-229 µm, 37.6%, p < 0.0001), but uncorrelated with VA gains, unlike stages 1 and 2 (respectively: -142 µm, 27.4%; - 5 µm, 12%; both p < 0.0001). Stage 4 showed no significant CST change. Baseline disorganization of retinal inner layers and focal damage of the ellipsoid zone/external limiting membrane did not influence VA improvement in stages 1 and 2. Treatment patterns varied, with 61% receiving anti-VEGF and 39% dexamethasone, influenced by DME stage, with no significant differences between therapeutic agents. CONCLUSION: The ESASO classification, which views the retina as a neurovascular unit and integrates multiple biomarkers, surpasses single biomarkers in predicting visual outcomes. Significant functional improvement occurred only in stages 1 and 2, suggesting reversible damage, whereas stages 3 and 4 likely reflect irreversible damage.

Global estimates on the number of people blind or visually impaired by cataract: a meta-analysis from 2000 to 2020.

BACKGROUND: To estimate global and regional trends from 2000 to 2020 of the number of persons visually impaired by cataract and their proportion of the total number of vision-impaired individuals. METHODS: A systematic review and meta-analysis of published population studies and gray literature from 2000 to 2020 was carried out to estimate global and regional trends. We developed prevalence estimates based on modeled distance visual impairment and blindness due to cataract, producing location-, year-, age-, and sex-specific estimates of moderate to severe vision impairment (MSVI presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60). Estimates are age-standardized using the GBD standard population. RESULTS: In 2020, among overall (all ages) 43.3 million blind and 295 million with MSVI, 17.0 million (39.6%) people were blind and 83.5 million (28.3%) had MSVI due to cataract blind 60% female, MSVI 59% female. From 1990 to 2020, the count of persons blind (MSVI) due to cataract increased by 29.7%(93.1%) whereas the age-standardized global prevalence of cataract-related blindness improved by -27.5% and MSVI increased by 7.2%. The contribution of cataract to the age-standardized prevalence of blindness exceeded the global figure only in South Asia (62.9%) and Southeast Asia and Oceania (47.9%). CONCLUSIONS: The number of people blind and with MSVI due to cataract has risen over the past 30 years, despite a decrease in the age-standardized prevalence of cataract. This indicates that cataract treatment programs have been beneficial, but population growth and aging have outpaced their impact. Growing numbers of cataract blind indicate that more, better-directed, resources are needed to increase global capacity for cataract surgery.

RETINAL MICROVASCULAR CHANGES IN PATIENTS WITH ACUTE LEUKEMIA.

PURPOSE: To evaluate the retinal circulation in patients with active acute leukemia, to correlate the perfusion metrics with systemic laboratory values, and to assess the vascular perfusion after leukemia remission. METHODS: Longitudinal study of 22 eyes from 12 patients with acute leukemia; healthy eyes were recruited as control subjects. All patients underwent optical coherence tomography angiography at baseline. Optical coherence tomography angiography was repeated in case of morphologic leukemia remission. RESULTS: Patients' age ranged from 37 to 74 years. All participants had a 20/20 vision. In all leukemic eyes, optical coherence tomography angiography detected vascular alterations in the macula and the peripapillary region. Vessel density values in the superficial capillary plexus were lower in patients with leukemia than control subjects (46.8 ± 3.6 vs. 49.2 ± 2%, P = 0.08), irrespective of the presence of leukemic retinopathy (7 eyes, 32%). Lower vessel density was associated with lower white blood cells ( P = 0.09) and lower platelets ( P = 0.001). Reappearance of small capillaries, increase in vessel density, reduction in vessel diameter, and increase in fractal dimension were seen after remission. CONCLUSION: Subclinical, reversible reduction in vessel density and complexity on optical coherence tomography angiography occurs in patients with active acute leukemia and is presumably associated with bone marrow function failure. Further studies are warranted to explore its functional and prognostic significance.

CLINICAL ASSOCIATIONS AND PROGNOSTIC IMPLICATIONS OF REPAIR TISSUE PROLIFERATION IN EYES WITH RETINAL PIGMENT EPITHELIUM TEARS.

PURPOSE: To investigate demographic and clinical factors influencing the longitudinal changes of retinal pigment epithelium (RPE) dehiscence area after RPE tears, including the presence of RPE tear-associated repair proliferation (TARP), and identify factors associated with TARP development over follow-up. METHODS: Retrospective, single-center, observational cohort study of patients with a history of macular neovascularization and RPE tear. The area of RPE dehiscence was measured on repeated short-wavelength fundus autofluorescence imaging. Associations between covariates and RPE dehiscence areas were tested with multivariable linear mixed models. Associations between TARP development and clinical variables were investigated with Cox regression models. Factors associated with visual acuity changing rates were explored with linear mixed models. RESULTS: Thirty-seven eyes of 36 patients were included in this study and followed for a median time of 18 months. Tear-associated repair proliferation was identified in 27 eyes (73%). The median time for TARP detection was 112 days; none of the investigated factors was significantly associated with TARP occurrence. The presence of TARP (estimate: -0.042 mm2/month; P = 0.001) and female gender (estimate: -0.035 mm2/month; P = 0.006) were associated with slower rates of RPE dehiscence enlargement over time. Faster rates of visual improvement were observed in eyes with TARP compared with those without TARP (estimate = -0.010 logarithm of the minimum angle of resolution/month if TARP was present; P = 0.008). CONCLUSION: Retinal pigment epithelium tear repair with TARP and female gender were associated with slower RPE degeneration after RPE tears. The presence of TARP was associated better visual prognosis. Additional research on factors promoting TARP development may have therapeutic and prognostic implications.

Superficial capillary perfusion on optical coherence tomography angiography differentiates moderate and severe nonproliferative diabetic retinopathy.

PURPOSE: To identify objective optical coherence tomography angiography (OCTA) parameters that characterize the spectrum of non-proliferative diabetic retinopathy (NPDR), especially those that distinguish moderate from severe NPDR. METHODS: Sixty eyes of 60 patients with treatment-naïve NPDR (mild: 21, moderate: 21, severe: 18), 23 eyes with diabetes and no retinopathy, and 24 healthy control eyes were enrolled. OCTA slabs were segmented into superficial (SCP), middle (MCP), and deep capillary plexus (DCP) and thresholded by a new method based on DCP skeletonized vessel length. The foveal avascular zone (FAZ) area, parafoveal vessel density (VD), and adjusted flow index (AFI) from all three capillary layers and the vessel length density (VLD) of the SCP were compared between each severity group, after adjusting for age and image quality. RESULTS: All vessel density markers decreased with increasing severity of NPDR. SCP VD and VLD demonstrated significant differences between eyes with diabetes with no retinopathy and mild NPDR (p = 0.001 and p < 0.001, respectively), as well as between moderate vs. severe NPDR (p = 0.004 and p = 0.009, respectively). MCP VD significantly decreased between moderate and severe NPDR (p = 0.01). AFI significantly increased in the SCP and showed a decreasing trend in the MCP and DCP with increasing NPDR severity. CONCLUSIONS: Changes in the SCP VD, SCP VLD, and MCP VD can distinguish severe NPDR from lower-risk stages. SCP changes may be more reliable due to their lower susceptibility to noise and projection artifacts. Thresholding OCTA images based on DCP skeletonized vessel length showed less variability in moderate and severe NPDR. Additional studies are warranted to validate this new thresholding method.

Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis.

BACKGROUND: Contemporary data for causes of vision impairment and blindness form an important basis of recommendations in public health policies. Refreshment of the Global Vision Database with recently published data sources permitted modelling of cause of vision loss data from 1990 to 2015, further disaggregation by cause, and forecasts to 2020. METHODS: In this systematic review and meta-analysis, we analysed published and unpublished population-based data for the causes of vision impairment and blindness from 1980 to 2014. We identified population-based studies published before July 8, 2014, by searching online databases with no language restrictions (MEDLINE from Jan 1, 1946, and Embase from Jan 1, 1974, and the WHO Library Database). We fitted a series of regression models to estimate the proportion of moderate or severe vision impairment (defined as presenting visual acuity of <6/18 but ≥3/60 in the better eye) and blindness (presenting visual acuity of <3/60 in the better eye) by cause, age, region, and year. FINDINGS: We identified 288 studies of 3 983 541 participants contributing data from 98 countries. Among the global population with moderate or severe vision impairment in 2015 (216·6 million [80% uncertainty interval 98·5 million to 359·1 million]), the leading causes were uncorrected refractive error (116·3 million [49·4 million to 202·1 million]), cataract (52·6 million [18·2 million to 109·6 million]), age-related macular degeneration (8·4 million [0·9 million to 29·5 million]), glaucoma (4·0 million [0·6 million to 13·3 million]), and diabetic retinopathy (2·6 million [0·2 million to 9·9 million]). Among the global population who were blind in 2015 (36·0 million [12·9 million to 65·4 million]), the leading causes were cataract (12·6 million [3·4 million to 28·7 million]), uncorrected refractive error (7·4 million [2·4 million to 14·8 million]), and glaucoma (2·9 million [0·4 million to 9·9 million]). By 2020, among the global population with moderate or severe vision impairment (237·1 million [101·5 million to 399·0 million]), the number of people affected by uncorrected refractive error is anticipated to rise to 127·7 million (51·0 million to 225·3 million), by cataract to 57·1 million (17·9 million to 124·1 million), by age-related macular degeneration to 8·8 million (0·8 million to 32·1 million), by glaucoma to 4·5 million (0·5 million to 15·4 million), and by diabetic retinopathy to 3·2 million (0·2 million to 12·9 million). By 2020, among the global population who are blind (38·5 million [13·2 million to 70·9 million]), the number of patients blind because of cataract is anticipated to rise to 13·4 million (3·3 million to 31·6 million), because of uncorrected refractive error to 8·0 million (2·5 million to 16·3 million), and because of glaucoma to 3·2 million (0·4 million to 11·0 million). Cataract and uncorrected refractive error combined contributed to 55% of blindness and 77% of vision impairment in adults aged 50 years and older in 2015. World regions varied markedly in the causes of blindness and vision impairment in this age group, with a low prevalence of cataract (<22% for blindness and 14·1-15·9% for vision impairment) and a high prevalence of age-related macular degeneration (>14% of blindness) as causes in the high-income subregions. Blindness and vision impairment at all ages in 2015 due to diabetic retinopathy (odds ratio 2·52 [1·48-3·73]) and cataract (1·21 [1·17-1·25]) were more common among women than among men, whereas blindness and vision impairment due to glaucoma (0·71 [0·57-0·86]) and corneal opacity (0·54 [0·43-0·66]) were more common among men than among women, with no sex difference related to age-related macular degeneration (0·91 [0·70-1·14]). INTERPRETATION: The number of people affected by the common causes of vision loss has increased substantially as the population increases and ages. Preventable vision loss due to cataract (reversible with surgery) and refractive error (reversible with spectacle correction) continue to cause most cases of blindness and moderate or severe vision impairment in adults aged 50 years and older. A large scale-up of eye care provision to cope with the increasing numbers is needed to address avoidable vision loss. FUNDING: Brien Holden Vision Institute.

Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis.

BACKGROUND: Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment. METHODS: We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12). FINDINGS: Globally, of the 7·33 billion people alive in 2015, an estimated 36·0 million (80% uncertainty interval [UI] 12·9-65·4) were blind (crude prevalence 0·48%; 80% UI 0·17-0·87; 56% female), 216·6 million (80% UI 98·5-359·1) people had moderate to severe visual impairment (2·95%, 80% UI 1·34-4·89; 55% female), and 188·5 million (80% UI 64·5-350·2) had mild visual impairment (2·57%, 80% UI 0·88-4·77; 54% female). Functional presbyopia affected an estimated 1094·7 million (80% UI 581·1-1686·5) people aged 35 years and older, with 666·7 million (80% UI 364·9-997·6) being aged 50 years or older. The estimated number of blind people increased by 17·6%, from 30·6 million (80% UI 9·9-57·3) in 1990 to 36·0 million (80% UI 12·9-65·4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38·4%), population ageing after accounting for population growth (34·6%), and reduction in age-specific prevalence (-36·7%). The number of people with moderate and severe visual impairment also increased, from 159·9 million (80% UI 68·3-270·0) in 1990 to 216·6 million (80% UI 98·5-359·1) in 2015. INTERPRETATION: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected. These observations, plus a very large contribution from uncorrected presbyopia, highlight the need to scale up vision impairment alleviation efforts at all levels. FUNDING: Brien Holden Vision Institute.

EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. METHODS: All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. PRIMARY OUTCOME: changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 µm, 1000 µm, and 1,500 µm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. RESULTS: Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 µm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 µm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P < 0.001). Statistically significant reduction in choroidal thickness was registered in the nasal 500, 1000, and 1,500 µm from the fovea, corresponding to the papillomacular region (from 169.6 ± 45.3 to 153.9 ± 46.9, P < 0.001). CONCLUSION: Intravitreal ranibizumab injections did not affect retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

CLINICAL SPECTRUM OF MACULAR-FOVEAL CAPILLARIES EVALUATED WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe macular-foveal capillaries (MFC) by means of optical coherence tomography angiography and to identify the clinical spectrum of this angiographic feature. METHODS: Patients with MFC presenting at the Medical Retina & Imaging Unit of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent a complete ophthalmologic examination that included slit-lamp examination, fundus examination, measurement of best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). Fluorescein angiography was performed in selected cases. Optical coherence tomography angiography was performed through Zeiss prototype (AngioPlex, CIRRUS HD-OCT models 5000; Carl Zeiss Meditec, Inc, Dublin, OH). RESULTS: Twelve eyes of 10 consecutive white patients (5 men and 5 women; 50%) presenting MFC were included. Mean age was 66.2 ± 10.2 years (range, 53-79 years); mean best-corrected visual acuity was 0.1 ± 0.13 logarithm of the minimum angle of resolution (range, 0-0.4 logarithm of the minimum angle of resolution, corresponding to 20/20 to 20/50). Mean central macular thickness was 348 ± 57.6 µm. Two patients were affected by macular pucker, two by postsurgical macular edema, two by age-related macular degeneration, one by diabetic retinopathy, one by dome-shaped macula, one presented with chronic serous chorioretinopathy, and one with branch artery occlusion. Six eyes disclosed a complete absence of the foveal avascular zone, whereas the six other cases showed a partial foveal avascularity. No significant difference was found between complete and incomplete MFC with regards to best-corrected visual acuity (P = 0.272) and central macular thickness (P = 0.870). CONCLUSION: Cases of persistent MFC are heterogeneous in demographic characteristics, fundus appearance, and visual function. However, MFC, presenting either as complete absence of the foveal avascular zone or only partial foveal avascularity, may complicate different retinal abnormalities or represents a coincident finding.

Tirofiban as treatment for acute retinal artery occlusion following internal carotid artery flow diverter implantation.

PURPOSE: To report a favorable outcome of branch retinal artery occlusion (BRAO) treated by means of early administration of tirofiban, a glycoprotein IIb-IIIa platelet receptor inhibitor. METHODS: Case report. RESULTS: A 65-year-old woman developed dramatic visual impairment in her left eye secondary to BRAO after left internal carotid artery endovascular reconstruction with flow diverter stent implant; visual acuity was hand motion. A dose of intravenous tirofiban was injected 10 minutes after symptoms onset. Fourteen hours after drug infusion, retinal fluorescein angiography revealed a well-perfused macula with a partial reperfusion of the inferior temporal branch of the central retinal artery; visual acuity was 20/20 in both eyes. CONCLUSIONS: This case supports the effectiveness of tirofiban in secondary BRAO in neurosurgery and may open its usage to further research.

MP1 AND MAIA FUNDUS PERIMETRY IN HEALTHY SUBJECTS AND PATIENTS AFFECTED BY RETINAL DYSTROPHIES.

PURPOSE: To compare retinal sensitivity obtained with MP1 and MAIA microperimeters in patients affected by retinal dystrophies (RD) and in healthy subjects. METHODS: Thirty-six patients affected by RD and 25 healthy subjects were considered for the study. All patients and controls underwent a complete ophthalmic examination including fundus-related perimetry, performed by means of two microperimeters, the MP1 (Nidek Technologies) and the MAIA (CenterVue). Main outcome of the study was the comparison of retinal sensitivity. Such comparison was performed converting the MP1 decibel (dB) values to their MAIA equivalent dB values. RESULTS: Mean retinal sensitivity in patients affected by RD was 5.68 ± 6.08 dB (mean ± SD) on MP1 (9.66 ± 10.06 dB converted to their equivalent MAIA values) and 14.66 ± 9.37 dB on MAIA (P < 0.0001). Mean retinal sensitivity in healthy subjects was 18.46 ± 3.10 dB on MP1 (22.44 ± 7.08 dB on their converted equivalent MAIA values) and 28.52 ± 1.12 dB on MAIA (P < 0.0001). Thirty eyes affected by RD (41%) showed retinal areas characterized by sensitivity under 1 dB on MP1, whereas the MAIA examination of the same areas revealed a mean retinal sensitivity of 4.7 dB. Moreover, 28 of these eyes disclosed also areas of absolute scotoma on MP1, but examining the same areas on MAIA, just 13 of these eyes (46%) disclosed an absolute scotoma. In addition, in a subgroup of 6 eyes affected by RD (8%) showing a retinal sensitivity of 20 dB on MP1, the corresponding value on MAIA varied from 26.3 dB to 30.0 dB, with a mean value of 27.8 ± 1.3 dB. CONCLUSION: The MAIA microperimeter provides a more accurate characterization of functional impairment in RD with respect to the MP1 system, especially in cases with low and high retinal sensitivity. MAIA microperimeter could reveal particularly useful in precisely identifying and monitoring subtle changes in retinal sensitivity, especially in view of the availability of therapies aiming at a functional rescue in patients with RD.

Dehydroepiandrosterone decreases the age-related decline of the in vitro fertilization outcome in women younger than 40 years old.

BACKGROUND: With infertility populations rapidly aging, treatments improving pregnancy chances assume increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy rates and lower miscarriage rates in women with diminished ovarian function. This study was planned to evaluate whether pretreatment with DHEA may improve in vitro fertilization (IVF) parameters and pregnancy outcomes in infertile women with advanced reproductive age and normal ovarian reserve. METHODS: In this double-blind, randomized, placebo-controlled study, 109 infertile patients aging 36-40 years old were selected to undergo the long protocol IVF. Eight weeks before starting the IVF cycle and during treatment, patients in Group 1 received 75 mg of DHEA once a day; patients in control group (Group 2) received placebo. The primary endpoint of the study was number of clinical pregnancy, live birth and miscarriage rates; secondary endpoint was modification of standard IVF parameters, including stimulation duration (days of rhFSH administration), E2 on HCG-day, endometrial thickness, number of retrieved oocytes, metaphase II oocytes, number of transferred embryos and score of leading embryos transferred. RESULTS: Patients in the DHEA group had a significantly higher live birth rate compared with controls (P<0.05). Conversely, miscarriage rate was higher for patients in the control group (P<0.05). CONCLUSIONS: DHEA supplementation may significantly improve IVF outcomes in infertile women with advanced reproductive age and normal ovarian reserve.