The socioeconomic epidemiology of inherited retinal diseases in Portugal.

BACKGROUND: Inherited retinal diseases (IRDs) are a group of rare degenerative disorders of the retina that can lead to blindness from birth to late middle age. Knowing the target population and its resources is essential to better plan support measures. The aim of this study was to evaluate the socioeconomic characteristics of regions in Portugal where IRD patients reside to inform the planning of vision aid and rehabilitation intervention measures. RESULTS: This study included 1082 patients from 973 families, aged 3 to 92 years, with a mean age of 44.8 ± 18.1 years. Patients living with an IRD were identified in 190 of the 308 municipalities. According to this study, the estimated IRD prevalence in Portugal was 10.4 per 100,000 inhabitants, and by municipalities, it ranged from 0 to 131.2 per 100,000 inhabitants. Overall, regions with a higher prevalence of IRD have a lower population density (r=-0.371, p < 0.001), a higher illiteracy rate (r = 0.404, p < 0.001) and an overall older population (r = 0.475, p < 0.001). Additionally, there is a lower proportion of doctor per capita (r = 0.350, p < 0.001), higher social security pensions beneficiaries (r = 0.439, p < 0.001), worse water quality for human consumption (r=-0.194, p = 0.008), fewer audiences at the cinema (r=-0.315, p < 0.001) and lower proportion of foreign guests in tourist accommodations (r=-0.287, p < 0.001). CONCLUSION: The number of identified patients with IRD varied between regions. Using data from national statistics (PORDATA), we observed differences in socioeconomic characteristics between regions. Multiple targeted aid strategies can be developed to ensure that all IRD patients are granted full clinical and socioeconomic support.

Serum and Vitreous Levels of Placenta Growth Factor in Diabetic Retinopathy Patients: Correlation With Disease Severity and Optical Coherence Tomographic Parameters.

Purpose The primary objective of this study was to compare placenta growth factor (PlGF) levels in the serum and vitreous of diabetic retinopathy (DR) patients to non-diabetic controls. Additionally, the study aimed to establish associations between serum and vitreous PlGF concentrations and to examine the correlation between vitreous PlGF in DR patients and morphological parameters. Methods This study included serum and vitreous samples from 38 patients, including 21 patients with DR and 17 non-diabetic controls. The control group included non-diabetic patients with rhegmatogenous retinal detachment with retinal tears secondary to posterior vitreous detachment or trauma. PlGF levels were quantified in vitreous and serum samples using an enzyme-linked immunosorbent assay (ELISA). Optical coherence tomography (OCT) scans from DR patients were evaluated to measure the central retinal thickness (CRT) and macular volume (MV). Results DR patients had significantly higher mean vitreous PlGF levels compared to non-DR patients (70.0±39.2 vs. 46.47±9.7 pg/mL, p-value=0.004). However, no significant increase in mean serum PlGF levels was observed in DR patients (p-value=0.232). Within the DR group, proliferative DR (PDR) patients presented significantly higher vitreous PlGF levels than non-PDR (NPDR) patients (76.5±41.0 vs. 42.5±5.0 pg/mL, p-value=0.009). There was no association between serum and vitreous PlGF levels. The correlation between vitreous PlGF levels and morphological parameters was rsp=0.175, p-value=0.488 for CRT, and rsp=0.288, p-value=0.262 for MV. Conclusion This study emphasizes the important role of PlGF in neovascularization, specifically highlighting its overexpression exclusively in vitreous from PDR patients. The observed increase in PlGF levels may be indicative of disease severity. The lack of correlation between vitreous and serum PlGF levels suggests a potential dissociation between intravitreal and systemic PlGF synthesis. Consequently, targeting PlGF in therapeutic approaches may offer an additional strategy for ocular pathologies with a neovascular component.

Genetic profile of syndromic retinitis pigmentosa in Portugal.

PURPOSE: Retinitis pigmentosa (RP) comprises a genetically and clinically heterogeneous group of inherited retinal degenerations, where 20-30% of patients exhibit extra-ocular manifestations (syndromic RP). Understanding the genetic profile of RP has important implications for disease prognosis and genetic counseling. This study aimed to characterize the genetic profile of syndromic RP in Portugal. METHODS: Multicenter, retrospective cohort study. Six Portuguese healthcare providers identified patients with a clinical diagnosis of syndromic RP and available genetic testing results. All patients had been previously subjected to a detailed ophthalmologic examination and clinically oriented genetic testing. Genetic variants were classified according to the American College of Medical Genetics and Genomics; only likely pathogenic or pathogenic variants were considered relevant for disease etiology. RESULTS: One hundred and twenty-two patients (53.3% males) from 100 families were included. Usher syndrome was the most frequent diagnosis (62.0%), followed by Bardet-Biedl (19.0%) and Senior-Løken syndromes (7.0%). Deleterious variants were identified in 86/100 families for a diagnostic yield of 86.0% (87.1% for Usher and 94.7% for Bardet-Biedl). A total of 81 genetic variants were identified in 25 different genes, 22 of which are novel. USH2A and MYO7A were responsible for most type II and type I Usher syndrome cases, respectively. BBS1 variants were the cause of Bardet-Biedl syndrome in 52.6% of families. Best-corrected visual acuity (BCVA) records were available at baseline and last visit for 99 patients (198 eyes), with a median follow-up of 62.0 months. The mean BCVA was 56.5 ETDRS letters at baseline (Snellen equivalent ~ 20/80), declining to 44.9 ETDRS letters (Snellen equivalent ~ 20/125) at the last available follow-up (p < 0.001). CONCLUSION: This is the first multicenter study depicting the genetic profile of syndromic RP in Portugal, thus contributing toward a better understanding of this heterogeneous disease group. Usher and Bardet-Biedl syndromes were found to be the most common types of syndromic RP in this large Portuguese cohort. A high diagnostic yield was obtained, highlighting current genetic testing capabilities in providing a molecular diagnosis to most affected individuals. This has major implications in determining disease-related prognosis and providing targeted genetic counseling for syndromic RP patients in Portugal.

Bull's Eye Maculopathy in Near-Infrared Reflectance as An Early Sign of Hydroxychloroquine Toxicity.

Hydroxychloroquine (HCQ) ocular toxicity is rare but severe, and progression can occur even after termination of therapy. Case reports have suggested that a bull's eye maculopathy detected by near-infrared reflectance (NIR) may indicate early HCQ toxicity. This retrospective cross-sectional study evaluated patients treated with HCQ who underwent routine screening with optical coherence tomography (OCT), fundus autofluorescence (FAF) and 10-2 perimetry. NIR images captured alongside OCT were subsequently graded independently by 2 masked graders for the presence of bull's eye maculopathy, and the result was compared to the outcome of the screening. A total of 123 participants (246 eyes) were included, and 101 (90%) were female. The patients' mean age was 55.2 ± 13.8 years. The mean time of HCQ usage was 84.0 ± 72.3 months, and the mean weekly dose was 2327 ± 650 mg. Two eyes showed toxicity in all 3 routine screening exams, with one patient suspending HCQ. The prevalence of bull´s eye lesions in NIR was 13% (33 eyes) with substantial intergrader agreement, a 71.3% specificity and 88.0% negative predictive value for HCQ toxicity. We suggest that NIR changes may be a sign of early HCQ toxicity. The detection of NIR bull´s eye lesions may warrant an increased screening frequency.

Challenges, facilitators and barriers to the adoption and use of a web-based national IRD registry: lessons learned from the IRD-PT registry.

Rare disease registries increase research accessibility for patients, while providing clinicians/investigators with a coherent data ecosystem necessary to boost research and patient care. The IRD-PT registry is a national, web-based, interoperable registry for inherited retinal degenerations (IRDs) designed to generate scientific knowledge and collect high-quality data on the epidemiology, genomic landscape and natural history of IRDs in Portugal. In two years, the number of enrolled patients almost doubled (537 to 1060). Still, the registry has a lower-than-expected adoption rate, with only 4 centers across Portugal actively enrolling patients. This highlights a strong need to understand factors that may be hindering the registry's nationwide adoption. The purpose of this manuscript is to analyze challenges, facilitators and barriers to the adoption and use of the IRD-PT registry, and to discuss avenues for improvement, focusing on keeping the registry sustainable in the long run. We believe that this exercise may help other rare disease registries to improve user adherence and engagement, ultimately contributing to develop more sustainable and successful registries in the field.

Sensitivity and specificity of MultiColor imaging in detecting proliferative diabetic retinopathy.

PURPOSE: To evaluate the accuracy of MultiColor imaging (MC) compared to fluorescein angiography (FA) in detecting proliferative diabetic retinopathy (PDR) and associated diabetic retinopathy features. METHODS: Fifty-nine eyes from 38 PDR patients were included. MC images were reviewed by 2 independent masked graders. A qualitative analysis based on the following features was performed: neovascular complexes (NVC), disc neovascularization (NVD), neovascularization elsewhere (NVE), microaneurysm (MA), intraretinal hemorrhage (IRH), vitreous hemorrhage (VH), preretinal hemorrhage (PRH), fibrosis, hard exudates (HE), epiretinal membrane (ERM), diabetic macular edema (DME), ischemia and laser spots (LS). Measures of diagnostic accuracy compared to FA were determined. RESULTS: The sensitivity for the detection of NVC using MC was 95.1%, with a specificity of 40.0%, positive predictive value (PPV) of 92.9% and negative predictive value (NPV) of 50.0%. Sensitivity and specificity were higher in detecting NVD (88.9% and 76.9%) while NVE registered higher PPV (88.9%). MC was highly sensitive in detecting IRH, HE, ERM and LS (100%), MA (98.0%) and fibrosis (95.5%). Highest specificity was found for VH (100.0%), DME (100.0%), PRH (98.1%) and LS (89.5%). The area under the receiver-operating characteristic analysis of MC was excellent in NVD (0.83, 95% confidence interval (CI), 0.71-0.95, p < 0.001), IRH (0.89, 95% CI 0.74-1.00, p < 0.001), VH (0.81, 95% CI 0.60-1.00, p = 0.005) and PRH (0.89, 95% CI 0.68-1.00, p = 0.004) and outstanding in LS detection (0.95, 95% CI 0.87-1.00, p < 0.001). These results are likely due to the contrast and quality of the MC since better discrimination is enabled by the green wavelength. CONCLUSION: MC is useful in evaluation of PDR patients and can complement noninvasive imaging. MC detected some PDR features more accurately than FA such as NVD, IRH, VH, PRH, and LS.

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

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

An uncommon cold of the retina.

A 39-year-old woman with progressive loss of vision left eye was referred for evaluation. Notably, she had been diagnosed with COVID-19 two weeks beforehand. Examination and ancillary testing confirmed atypical multifocal evanescent white dot syndrome. Possible other masquerades were excluded. A few weeks later, visual acuity improved in the left eye and symptoms resolved together with normalization of ancillary testing, including visual fields.

Update on Optical Coherence Tomography and Optical Coherence Tomography Angiography Imaging in Proliferative Diabetic Retinopathy.

Proliferative diabetic retinopathy (PDR) is a major cause of blindness in diabetic individuals. Optical coherence tomography (OCT) and OCT-angiography (OCTA) are noninvasive imaging techniques useful for the diagnosis and assessment of PDR. We aim to review several recent developments using OCT and discuss their present and potential future applications in the clinical setting. An electronic database search was performed so as to include all studies assessing OCT and/or OCTA findings in PDR patients published from 1 January 2020 to 31 May 2021. Thirty studies were included, and the most recently published data essentially focused on the higher detection rate of neovascularization obtained with widefield-OCT and/or OCTA (WF-OCT/OCTA) and on the increasing quality of retinal imaging with quality levels non-inferior to widefield-fluorescein angiography (WF-FA). There were also significant developments in the study of retinal nonperfusion areas (NPAs) using these techniques and research on the impact of PDR treatment on NPAs and on vascular density. It is becoming increasingly clear that it is critical to use adequate imaging protocols focused on optimized segmentation and maximized imaged retinal area, with ongoing technological development through artificial intelligence and deep learning. These latest findings emphasize the growing applicability and role of noninvasive imaging in managing PDR with the added benefit of avoiding the repetition of invasive conventional FA.

Near-infrared reflectance imaging of neovascularization in proliferative diabetic retinopathy.

BACKGROUND: Blood is one of the main absorbers in the near-infrared spectrum and thus retinal vessels appear dark in near-infrared reflectance (NIR) images. Proliferative diabetic retinopathy (PDR) is characterized by abnormal neovascularization which also absorbs light and appears dark against a lighter fundus background. We analyzed neovascularization in PDR using NIR imaging, by observing changes in the neovascular complexes (NVCs) contrast and reflectivity over time. METHODS: Retrospective case series of 20 eyes of 17 patients with PDR who underwent NIR imaging with optical coherence tomography (OCT) using the Spectralis System. NVCs presence and activity was determined using clinical, tomographic and angiographic criteria. At baseline, all NVCs were qualitatively graded in the NIR image into 3 groups (absent, present and inactive and present and active) and their evolution over time was registered as progression, regression or same status. RESULTS: Twenty-seven NVCs were imaged, of which, 52% were neovascularization of the disc (NVD) and 48% were elsewhere (NVE). Consecutive NIR images were obtained from baseline to up to 5 time-points with a mean follow-up of 3.2 ± 1.7 years. All eyes underwent laser treatment and 30% had additional intravitreal therapy. Using NIR imaging, NVCs were classified at baseline as absent, present and inactive and present and active, respectively in 11, 4 and 85% of cases. NIR identified active neovascularization as hyporeflective irregular dark vessels originating from the retinal venules in NVE or from the disc in NVD. In all groups during follow-up, progression was identified as the development of new vascular hyporeflective dark fronds while regression was shown by reduced dark perfusion. Five eyes developed a wolf's jaw configuration with vascular hyporeflective new vessels and hyperreflective tissue from extensive fibrosis. Fibrosis was more apparent in later images, reaching 86%. In 3 cases (11%), the NVC was no longer seen in NIR, although was still identifiable on OCT over the NVC area. CONCLUSIONS: NIR is a non-invasive imaging modality commonly performed alongside OCT and frequently overlooked which can be useful to evaluate NVCs in PDR. Changes in NVC contrast and reflectivity due to blood perfusion can help in the detection and monitoring of diabetic proliferative disease and aid clinicians in daily practice.

Optical Coherence Tomography Angiography Features of Neovascularization in Proliferative Diabetic Retinopathy.

PURPOSE: To describe features of neovascularization in proliferative diabetic retinopathy (PDR) using optical coherence tomography angiography (OCTA). METHODS: A retrospective case series was performed in 23 eyes from 21 patients who underwent OCTA of neovascular complexes (NVCs) due to PDR. Eyes were imaged with the DRI Triton swept-source OCTA, Avanti RTVue XR or Cirrus HD-OCT 5000 as part of routine clinical examination. Segmentation was adjusted to include vasculature between the vitreous cavity and the internal limiting membrane (ILM). The presence of NVCs was confirmed by clinical examination and multimodal imaging such as color or red-free fundus photography, fluorescein angiography, multicolor imaging or near-infrared reflectance. RESULTS: Thirty-five NVCs were imaged, of which, 34% were neovascularization of the disc (NVD) and 66% were neovascularization elsewhere (NVE). On structural OCT B-scans, NVE appeared as medium to highly reflective tissue that breached the ILM, while NVD showed highly reflective tissue protruding from the disc in a sea fan configuration. Flow signal was seen on OCTA in all cases of NVE and in 67% of NVD lesions. Areas with minimal or absent retinal flow signal identified retinal nonperfusion areas and were found adjacent to 87% of NVE. Intraretinal microvascular abnormalities (IRMAs) were noted next to 70% of NVE. Absent flow signal was seen in 4 NVD cases showing posterior shadowing and were considered inactive. CONCLUSION: OCTA appears useful for imaging NVCs, IRMAs, and retinal nonperfusion areas in eyes with diabetic retinopathy. This imaging modality enables noninvasive screening and monitoring of PDR and can obviate the need for additional testing in certain clinical settings.

Optical coherence tomography features of neovascularization in proliferative diabetic retinopathy: a systematic review.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness due to diabetic macular edema (DME) or complications of proliferative diabetic retinopathy (PDR). Optical coherence tomography (OCT) is a noninvasive imaging technique well established for DME but less used to assess neovascularization in PDR. Developments in OCT imaging and the introduction of OCT angiography (OCTA) have shown significant potential in PDR. OBJECTIVES: To describe the tomographic features of PDR, namely of neovascularization, both of the optic disc (NVD) and elsewhere (NVE), intraretinal microvascular abnormalities (IRMA), retinal nonperfusion areas (NPA), status of the posterior vitreous, vitreoschisis and vitreous and subhyaloid/sub-ILM hemorrhages. DATA SOURCES: Electronic database search on PubMed and EMBASE, last run on December 19th 2019. STUDY ELIGIBILITY CRITERIA PARTICIPANTS AND INTERVENTIONS: Publications assessing OCT and/or OCTA findings in PDR patients. All study designs were allowed except for case-reports, conference proceedings and letters. STUDY APPRAISAL: Newcastle-Ottawa Scale for observational studies was used for purposes of risk of bias assessment. RESULTS: From the 1300 studies identified, 283 proceeded to full-text assessment and 60 were included in this comprehensive review. OCT was useful in detecting NVD and NVE, such as in characterizing disease activity and response to laser and/or anti-VEGF therapies. The absence of posterior vitreous detachment seemed determinant for neovascular growth, with the posterior hyaloid acting as a scaffold. OCTA allowed a more detailed characterization of the neovascular complexes, associated NPA and disease activity, allowing the quantification of neovessel area and flow index. However, changes in OCTA blood flow signal following local therapies did not necessarily correlate with structural regression. Widefield and ultra-widefield OCTA were highly sensitive in the detection of PDR, adding value to disease staging and monitoring. Compared to fluorescein angiography, OCTA was more sensitive in detecting microvascular changes indicating disease progression. LIMITATIONS: Publication languages were restricted. Most included studies were observational and non-comparative. Risk of bias regarding case representativeness. CONCLUSIONS: OCT-based retinal imaging technologies are advancing rapidly and the trend is to be noninvasive and wide-field. OCT has proven invaluable in diagnosing, staging and management of proliferative diabetic disease with daily application in clinical and surgical practices.

The Outcomes of Switching from Short- to Long-Term Intravitreal Corticosteroid Implant Therapy in Patients with Diabetic Macular Edema.

BACKGROUND: First-line treatment for diabetic macular edema (DME) is usually with antivascular endothelial growth factor agents, followed by intravitreal corticosteroids as a second-line treatment option. Long-term corticosteroids may offer quality of life and effectiveness benefits over short-term implants. OBJECTIVES: To evaluate outcomes of patients with persistent or recurrent DME who switched from a short-term (dexamethasone) to a long-term (fluocinolone acetonide, FAc) corticosteroid intravitreal implant in a real-world setting. METHODS: This is a retrospective study in 9 Portuguese centers. An FAc intravitreal implant was administered according to product labeling. Effectiveness outcomes were mean change in visual acuity (VA; ETDRS letters), central retinal thickness (CRT; µm), and macular volume (MV; mm3). The safety outcome was mean change in intraocular pressure (IOP; mm Hg). All were analyzed at months 1 and 3, and then quarterly until month 24 after implantation. RESULTS: Forty-four eyes from 36 patients were analyzed. Mean duration of DME was 3.3 ± 1.9 years, and mean follow-up was 8 months. From baseline following FAc implantation, VA increased significantly at months 1 and 6 (mean +6.82 and +13.02 letters, respectively; p = 0.005), and last observation carried forward (LOCF; mean +8.3 letters; p = 0.002). CRT improved significantly at months 1 and 6 (mean -71.81 and -170.77 µm, respectively; p = 0.001), and LOCF (mean -121.46 µm; p = 0.001). MV was consistently, but not significantly, decreased from baseline to LOCF (mean -0.69 mm3; p = 0.062). The mean change in IOP was -0.25 and +0.88 mm Hg at months 1 and 6, respectively (p = 0.268), and +1.86 mm Hg at LOCF (p = 0.036). Increases were controlled with topical medication in most cases. CONCLUSIONS: The FAc intravitreal implant is effective in patients previously treated with short-term corticosteroid implants. Thus, after a suboptimal response to antiangiogenics or a short-term corticosteroid, a single FAc implant may be considered an effective and tolerable treatment that can improve long-term outcomes for patients with sight-threatening DME.

Evaluation of the growth factors VEGF-a and VEGF-B in the vitreous and serum of patients with macular and retinal vascular diseases.

VEGF-A and VEGF-B are proangiogenic and key regulating factors for blood vessel growth. This study aims to compare VEGF-A and VEGF-B levels in the serum and vitreous of patients with neovascular pathology versus non-neovascular pathology. Our findings showed vitreous VEGF-A and VEGF-B levels increased in patients with neovascular disease, with higher levels of VEGF-A compared to VEGF-B (p ≤ .05). In the diabetic retinopathy (DR) group, higher vitreous VEGF-A or VEGF-B were found in proliferative diabetic retinopathy (PDR) than in non-PDR. The strong correlation between VEGF-A and VEGF-B demonstrates a simultaneous pathological increase of cytokines (p < .001), suggesting besides VEGF-A, VEGF-B is another contributor to ocular pathologies involving angiogenesis. There was no correlation between vitreous and serum VEGF-A or VEGF-B; however, a correlation between vitreous (VEGF-A or VEGF-B) and macular volume (p < .05) in DR patients was found. Targeting VEGF-A and VEGF-B in macular and retinal vascular diseases, involving neovascularization, may improve treatment outcomes.

Vascular endothelial growth factors and placenta growth factor in retinal vasculopathies: Current research and future perspectives.

Vision loss due to disease or degeneration of the eye (retina, choroid, retinal veins, or macula) is a leading cause of blindness worldwide. In most cases, vision-threatening ocular diseases are accompanied by abnormal changes in the vasculature of the eye, especially the retina, and these conditions are collectively referred to as retinal vasculopathies. Impaired blood supply or hypoxia stimulates angiogenesis in the vascular and non-vascular sections of the eye, which results in neovascularization, leading to conditions such as diabetic retinopathy or age-related macular degeneration. Studies show that vascular endothelial growth factors: VEGF-A, VEGF-B, and placental growth factor (PlGF) are elevated in these diseases, and hence, these factors could be used as markers for disease prognosis and therapy. In this review, we discuss the function of these growth factors in normal development and disease, with focus on ocular disorders and emphasize the importance of accurately determining their levels in the vitreous and serum of patients for correct diagnosis and therapy.

VEGF-B Levels in the Vitreous of Diabetic and Non-Diabetic Patients with Ocular Diseases and Its Correlation with Structural Parameters.

Vascular endothelial growth factor B (VEGF-B) is one of the enigmatic members of the VEGF family. The knowledge gap about VEGF-B expression and how its levels are altered in diabetic eyes were the focus of this investigation that was addressed by comparing and correlating vitreous VEGF-B between diabetic and non-diabetic patients. VEGF-B levels were measured by enzyme-linked immunosorbent assay in vitreous samples (n = 33) from diabetic (n = 25) and non-diabetic (n = 8) patients. Results were compared between groups. Optical coherence tomography from diabetic patients was evaluated for central retinal thickness (CRT) and macular volume (MV). Mean vitreous VEGF-B concentration was higher in diabetic (18.82 ± 1.44 pg/mL ) vs. non-diabetic patients (17.90 ± 0.32 pg/mL) (p = 0.006), and in proliferative diabetic retinopathy (PDR) (19.03 ± 1.52 pg/mL) vs. non-PDR (NPDR) patients (18.18 ±0.96 pg/mL) (p = 0.025). In diabetic retinopathy (DR) patients, correlation between VEGF-B and CRT (µm) was positive and moderate: rs = 0.441 (p ≤ 0.05) and the correlation between VEGF-B and MV (mm³) was positive and robust: rs = 0.716 (p ≤ 0.01). VEGF-B levels are overexpressed in vitreous of diabetic patients, and the levels are higher in developed stages of DR. Correlation results show that CRT and MV increase with increased levels of VEGF-B. Targeting VEGF-B inhibition may have therapeutic beneficial implications.