Decrease In Retinal Thickness Research Articles

C9ORF72 Deficiency Results in Neurodegeneration in the Zebrafish Retina.

Hexanucleotide repeat expansions within the gene C9ORF72 are the most common cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This disease-causing expansion leads to a reduction in C9ORF72 expression levels in patients, suggesting loss of C9ORF72 function could contribute to disease. To further understand the consequences of C9ORF72 deficiency in vivo, we generated a c9orf72 mutant zebrafish line. Analysis of the adult female spinal cords revealed no appreciable neurodegenerative pathology such as loss of motor neurons or increased levels of neuroinflammation. However, detailed examination of adult female c9orf72-/- retinas showed prominent neurodegenerative features, including a decrease in retinal thickness, gliosis, and an overall reduction in neurons of all subtypes. Analysis of rod and cone cells within the photoreceptor layer showed a disturbance in their outer segment structure and rhodopsin mislocalization from rod outer segments to their cell bodies and synaptic terminals. Thus, C9ORF72 may play a previously unappreciated role in retinal homeostasis and suggests C9ORF72 deficiency can induce tissue specific neuronal loss.

A novel GCaMP6f-RCS rat model for studying electrical stimulation in the degenerated retina.

Background: Retinal prostheses aim to restore vision by electrically stimulating the remaining viable retinal cells in Retinal Degeneration (RD) cases. Research in this field necessitates a comprehensive analysis of retinal ganglion cells' (RGCs) responses to assess the obtained visual acuity and quality. Here we present a novel animal model which facilitates the optical recording of RGCs activity in an RD rat. This model can significantly enhance the functional evaluation of vision restoration treatments. Methods: The development of the novel rat model is based on crossbreeding a retinal degenerated Royal College of Surgeons (RCS) rat with a transgenic line expressing the genetic calcium indicator GCaMP6f in the RGCs. Characterization of the model was achieved using Optical Coherence Tomography (OCT) imaging, histology, and electroretinography (ERG) at the ages of 4, 8, and 12weeks. Additionally, optical recordings of RGCs function in response to ex-vivo subretinal electrical stimulations were performed. Results: Histological investigations confirmed the high expression of GCaMP6f in the RGCs and minimal expression in the inner nuclear layer (INL). OCT imaging and histological studies revealed the expected gradual retinal degeneration, as evident by the decrease in retinal thickness with age and the formation of subretinal debris. This degeneration was further confirmed by ERG recordings, which demonstrated a significant decrease in the b-wave amplitude throughout the degeneration process, culminating in its absence at 12weeks in the GCaMP6f-RCS rat. Importantly, the feasibility of investigating subretinal stimulation was demonstrated, revealing a consistent increase in activation threshold throughout degeneration. Furthermore, an increase in the diameter of the activated area with increasing currents was observed. The spatial spread of the activation area in the GCaMP6f-RCS rat was found to be smaller and exhibited faster activation dynamics compared with the GCaMP6f-LE strain. Conclusion: This novel animal model offers an opportunity to deepen our understanding of prosthetically induced retinal responses, potentially leading to significant advancements in prosthetic interventions in visual impairments.

Six-month results of 577 nm subthreshold micropulse laser therapy in non-center involving diabetic macular edema

BackgroundThis study aimed to evaluate the efficacy of 577 nm subthreshold micropulse laser (SML) therapy in patients with non-center involving diabetic macular edema (DME). MethodsTwenty-two eyes of 18 patients diagnosed with non-center involving DME were included in this prospective, observational study. The patient's baseline best corrected visual acuity (BCVA), maximum retinal thickness (MRT), central macular thickness (CMT), and the area of macular exudates were determined and re-evaluated at 1, 3, and 6 months after laser treatment. ResultsThere was no statistically significant change in BCVA at the 1st, 3rd and 6th months compared to the baseline in the follow-up (p = 0.067, p = 0.270, p = 0.027 according to Bonferroni correction p < 0,01). 1st, 3rd, and 6th month MRT was statistically significantly lower than baseline (p = 0,009, p = 0,006, p = 0,007). No statistically significant change was detected in CMT at the 1st, 3rd and 6th months compared to the baseline in the follow-up (p = 0.384, p = 0.794, p = 0.363). No statistically significant change in the area of macular exudates was detected at the 1st, 3rd, and 6th months compared to the baseline (p = 0.904, p = 0.444, p = 0.277). ConclusionsThis study observed a significant decrease in extrafoveal retinal thickness in patients with DME. There was no progression to central macular involvement, an increase in the area of exudates, and a decrease in BCVA in any patient. SML may be an effective alternative to conventional argon laser in non-center involving DME.

Short-term outcomes of treatment switch to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration.

To report short-term outcomes of treatment switch to faricimab in real-world patients with aflibercept-resistant neovascular age-related macular degeneration (AMD). Single-center, retrospective cohort study with chart-review using electronic injection database, electronic medical records, and optical coherence tomography (OCT) data from May to September 2023. A total of 50 eyes of 46 patients were analyzed. Faricimab treatment led to absence of fluid in 32% of the eyes and a reduction of fluid in 84% of the eyes. There was a statistically significant decrease in central retinal thickness (CRT) and pigment epithelial detachment (PED) height in those that responded to the switch (median difference: - 31μm, IQR: 55, p < 0.0001 and median difference: - 21μm, IQR: 36, p < 0.0001, respectively) and a statistically significant increase in CRT (median difference: + 19μm, IQR: 20, p = 0.0143) and no change in PED height (median difference: + 22μm, IQR: 64, p = 0.1508) in those that did not. Best-corrected visual acuity (BCVA) showed marginal decrease with low statistical significance. No ocular or systemic safety events were observed. Our findings suggest that switching to faricimab is generally safe and effective in patients with neovascular AMD who are otherwise difficult to treat and have residual fluid despite frequent injections with aflibercept. We observed a high rate of morphological response to the treatment switch, improvement of anatomical parameters with about one-third of patients having dry macula following a single injection, and a marginal change in BCVA. Sustainability of these results requires further investigation. ClinicalTrials.gov registration number: NCT06124677. Date of registration: 09/11/2023, retrospectively registered.

Ripa-56 protects retinal ganglion cells in glutamate-induced retinal excitotoxic model of glaucoma

Glaucoma is a prevalent cause of blindness globally, characterized by the progressive degeneration of retinal ganglion cells (RGCs). Among various factors, glutamate excitotoxicity stands out as a significant contributor of RGCs loss in glaucoma. Our study focused on Ripa-56 and its protective effect against NMDA-induced retinal damage in mice, aiming to delve into the potential underlying mechanism. The R28 cells were categorized into four groups: glutamate (Glu), Glu + Ripa-56, Ripa-56 and Control group. After 24 h of treatment, cell death was assessed by PI / Hoechst staining. Mitochondrial membrane potential changes, apoptosis and reactive oxygen species (ROS) production were analyzed using flow cytometry. The alterations in the expression of RIP-1, p-MLKL, Bcl-2, BAX, Caspase-3, Gpx4 and SLC7A11 were examined using western blot analysis. C57BL/6j mice were randomly divided into NMDA, NMDA + Ripa-56, Ripa-56 and control groups. Histological changes in the retina were evaluated using hematoxylin and eosin (H&E) staining. RGCs survival and the protein expression changes of RIP-1, Caspase-3, Bcl-2, Gpx4 and SLC7A11 were observed using immunofluorescence. Ripa-56 exhibited a significant reduction in the levels of RIP-1, p-MLKL, Caspase-3, and BAX induced by glutamate, while promoting the expression of Bcl-2, Gpx-4, and SLC7A1 in the Ripa-56-treated group. In our study, using an NMDA-induced normal tension glaucoma mice model, we employed immunofluorescence and H&E staining to observe that Ripa-56 treatment effectively ameliorated retinal ganglion cell loss, mitigating the decrease in retinal ganglion cell layer and bipolar cell layer thickness caused by NMDA. In this study, we have observed that Ripa-56 possesses remarkable anti- necroptotic, anti-apoptotic and anti-ferroptosis properties. It demonstrates the ability to combat not only glutamate-induced excitotoxicity in R28 cells, but also NMDA-induced retinal excitotoxicity in mice. Therefore, Ripa-56 could be used as a potential retinal protective agent.

Lipid‐lowering therapy in the treatment of massive hard exudates in type 1 diabetes

Aims/Purpose: Today there is no approved medical therapy for hard macular exudates in diabetes and unfortunately this pathology often leads to significant visual loss. Purpose of our study was to assess whether long‐term lipid‐lowering therapy with fenofibrate could reduce the number and extension of massive macular exudates in Type 1 diabetes patients.Methods: There were 46 (92 eyes) Type 1 diabetes persons (18–42 years) with diabetic maculopathy and massive hard exudates included in this study. HbA1C ranging from 6% to 9%. The mean visual acuity was 0.3 ± 0.1. Patients were divided into two groups: main (22 person) and control (24 person). Exclusion criteria: patients on lipid‐lowering drugs, oral contraceptive pills, hormone replacement therapy, pregnant woman, familial hypercholesterolemia, hypothyroidism, chronic liver and kidney disease. All patients in the main group received fenofibrate 145 mg once a day for 8 months, patients in control group had conventional therapy. All patients had undergone standard ophthalmological examination, fundus photos and OCT scanning on presentation and during follow‐up visits. Patients were followed at 2, 6, 12 and 18 months after the start of the treatment.Results: In the main group anatomic result expressed by the reduction of number and extension of hard exudates, decrease in central retinal thickness was achieved in 77% of patients (17 patients, 34 eyes). Central retinal thickness in the main group decreased from mean 392 mkm to 255 mkm ± 30 mkm. Good functional result was achieved in 64% of patients (28 eyes), where visual acuity increased from 0.3 to 0.5 ± 0.1. This effect was stable for the whole follow‐up period. In the control group 74% of patients had no anatomic neither functional changes. In 15% of patients mean visual acuity slightly improved from 0.3 to 0.4 ± 0.05 with decrease in central retinal thickness from mean 386 mkm to 320 mkm ± 30 mkm due to better compensation of the main disease. In 15% the number and extension of hard exudates increased with further vision deterioration. No fenofibrate side effects were noticed in either group.Conclusions: Fenofibrate in Type 1 diabetic patients diminishes number of macular hard exudates, reduces macular oedema, improves visual acuity with stable effect over the time.

Retinal thickness as sensitivity as biomarkers of neurodegeneration in moderate diabetic retinopathy

Aims/Purpose: To analyse total retinal thickness (RT) and inner retinal layers (IRL) in Type 2 diabetes mellitus (DM2) patients, measured with swept source OCT (SS‐OCT), and retinal sensibility with microperimetry.Methods: A total of 54 DM2 subjects with moderate diabetic retinopathy (DR) with no signs of diabetic macular oedema (DME) and 73 age‐matched healthy individuals were assessed by SS‐OCT to quantify retinal thickness in the nine macular areas of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Retinal sensibility was measured by microperimetry with MAIA.Results: Mean ages were 64.06 ± 11.98 years for the DM2 group and 60.79 ± 8.62 years for the control group. DM2 patients presented lower visual acuity (p &lt; 0.001), RT was significantly higher in the outer temporal area (260.70 ± 19.22 μm in the control group vs. 271.90 ± 37.61 μm in the DM2 group, with p = 0.01), and retinal nerve fibre layer (RNFL) was significantly lower in the outer nasal area (50.38 ± 8.20 μm vs. 45.17 ± 11.25 μm, p = 0.005). Ganglion cells and inner plexiform layers (GCL+) in the parafoveal areas were thinner in DM2 and RT, GCL+ and GCL+ with RNFL (GCL++) significantly diminished with age in the outer ring. A positive correlation between LDL‐C and RNFL and a negative correlation between HDL‐C levels and inner temporal and central RNFL thickness were detected. The central and inner nasal areas presented a negative correlation between RNFL (p = 0.015) and MAIA (p = 0.008), while the outer inferior area showed a positive correlation (p = 0.025).Conclusions: Retinal sensitivity and macular RNFL thickness decrease in DM2 with moderate DR with no DME. Its correlation suggests the existence of diabetic retinal neurodegeneration.

Patterns of Structural Changes in the Fundus Measured by Optical Coherence Tomography Angiography as Potential Markers of Acute Mountain Sickness.

To use optical coherence tomography angiography (OCTA) to assess the pattern of changes in retinal and choroidal blood flow and structure in healthy volunteers who quickly went from sea level to a plateau and to determine the parameters associated with acute mountain sickness (AMS). Forty-five individuals (89 eyes) were examined by OCTA and filled out the AMS questionnaire. One baseline examination was performed on the plain, followed by examinations at days 1, 3, and 5 after entering the plateau. Parameters were self-controlled to explore patterns of change, analyzed for correlation with AMS score, and modeled as a nomogram of AMS risk. On the plateau compared to the plain, vascular morphology showed dilated superficial macular retinal vessels and constricted deeper layers with increased vessel length density and fractal dimension; vessel density increased in all retinal strata and decreased in the choroidal macrovascular layer; and thickness increased except for a decrease in mean retinal thickness in the central macular sulcus. The rate of increase in retinal nerve fiber layer (RNFL) thickness in the inner and outer macular rings correlated with AMS score (r = -0.211). The nomogram showed moderate accuracy (AUC = 0.672) and consistency (C-index = 0.659) in assessing AMS risk. In high-altitude hypoxia, retinal vessels dilate and distort, resulting in increased blood flow density and thickness. Increased RNFL thickness in the paracentral macula may be a marker of low AMS risk. The changes in the retinal structure of the fundus can be used to assess the risk of developing AMS.

Real-world experience with brolucizumab in neovascular age-related macular degeneration over 2years: the REBA extension study.

To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting. Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24months of follow-up. Both treatment-naïve and switch therapy patients were included. All relevant data were collected. The primary outcome measure was changed in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included change in central subfield thickness (CST) and complications. The mean (SD) baseline BCVA was 48.4 (3.5) letters and 36.2 (7.1) letters in treatment-naïve group and switch therapy group, respectively. BCVA gain was + 9.2 (3.7) letters (p = 0.01) and + 7.7 (3.4) letters (p = 0.011), respectively. The change in mean (SD) CST has shown a significant decrease in retinal thickness in treatment-naïve group (from 432.5 (68.4) to 283.0 (51.3) µm; p = 0.018) and in switch therapy group (from 452.5 (40.5) to 271.0 (43.4) µm; p = 0.011) group. One switch patient developed vascular occlusion and another a macular hole after the fifth brolucizumab injection as reported in the primary study. Both patients recovered uneventfully. Three patients demonstrated reversible intraocular inflammation between months 10 and 24. Patients showed a significant anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Overall, 5 significant untoward events were noted.

Retinal thickness and fundus blood flow density changes in chest pain subjects with dyslipidemia.

To assess the retinal thickness and fundus blood flow density changes in chest pain patients with dyslipidemia using optical coherence tomography angiography (OCTA). All subjects with chest pain as the main symptom accepted a comprehensive ophthalmological examination. According to the serum lipid levels, the participants were divided into the control group and the dyslipidemia group. The retina thickness and fundus blood flow density were determined using OCTA. The study enrolled 87 left eyes from 87 adults with dyslipidemia and 87 left eyes from age- and sex-matched participants without dyslipidemia. The retina of dyslipidemia subjects was significantly thinner than that of the controls in the inferior (P=0.004 and P=0.014, respectively) and temporal (P=0.015 and P=0.019, respectively) regions, both inner and outer layers. In terms of blood flow density in the macula or optic disk, there was a decreasing trend in the dyslipidemia group compared with the control group, especially in the inferior and temporal regions. Dyslipidemia may contribute to the decrease in retinal thickness and fundus blood flow density. Further validation of the association between abnormal lipid metabolism and fundus microcirculation alterations needs to be carried out in chest pain patients.

Pharmacogenetic Association between Allelic Variants of the Autophagy-Related Genes and Anti-Vascular Endothelial Growth Factor Treatment Response in Neovascular Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of late-onset blindness in elderly. The occurrence and development of AMD is a multifactorial complex process where autophagy plays an important role. The first-line drugs for neovascular AMD (nAMD) are inhibitors of VEGF, with up to 30% of patients having an incomplete response to treatment. Genetic factors may influence the response to anti-VEGF therapy and explain treatment outcome variability. We aimed to estimate the role of polymorphic markers of the MTOR (rs1064261, rs1057079, rs11121704, rs2295080), SQSTM1 (rs10277), ULK1 (rs11246867, rs3088051), MAP1LC3A (rs73105013) and ATG5 (rs573775) genes in the development of nAMD and the efficacy of anti-VEGF therapy response. Genotyping by allele-specific PCR was performed in 317 controls and 315 nAMD patients in the Russian population. Of them, 196 treatment-naive nAMD patients underwent three monthly intravitreal injections (IVIs) of aflibercept. Genotypic frequencies were compared with OCT markers of therapy effectiveness and best-corrected visual acuity (BCVA) measures. The main outcomes were the BCVA gain and decrease in central retinal thickness (CRT). MTOR-rs1057079-C, MTOR-rs11121704-C and MTOR-rs2295080-G alleles were associated with an increased risk of nAMD. The BCVA was increased in 117 (59.7%) patients by 10 [5-20] letters, did not changed in 59 (30.1%), and was decreased in 20 (10.2%) patients. ULK1-rs3088051 was associated with BCVA change. Among patients with the TT and CT genotypes for ULK1-rs3088051, an improvement in visual acuity was noted in 67.6% and 53.8% of cases, while in patients with the CC genotype, an increase in BCVA was recorded in 37.5% of cases (p = 0.01). The decrease in CRT was associated with SQSTM1-rs10277 (p = 0.001): it was significantly higher in TT (93 [58-122] mkm) and CT (66 [30-105] mkm) carriers compared to the CC genotype (47 [24-68] mkm). Other SNPs did not show significant associations with the outcome of anti-VEGF treatment. MTOR gene polymorphisms are moderately associated with the risk of nAMD. SQSTM1-rs10277 and ULK1-rs3088051 may influence short-term response to intravitreal anti-VEGF treatment. The results suggest that autophagy could be a target for future drugs to overcome resistance to anti-VEGF therapy.

Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury.

Abstract JOURNAL/nrgr/04.03/01300535-202407000-00042/figure1/v/2023-11-20T171125Z/r/image-tiff Elevated intraocular pressure (IOP) is one of the causes of retinal ischemia/reperfusion injury, which results in NLRP3 inflammasome activation and leads to visual damage. Homer1a is reported to play a protective role in neuroinflammation in the cerebrum. However, the effects of Homer1a on NLRP3 inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown. In our study, animal models were constructed using C57BL/6J and Homer1flox/ –/Homer1a+/ –/Nestin-Cre+/ – mice with elevated IOP-induced retinal ischemia/reperfusion injury. For in vitro experiments, the oxygen-glucose deprivation/reperfusion injury model was constructed with Müller cells. We found that Homer1a overexpression ameliorated the decreases in retinal thickness and Müller cell viability after ischemia/reperfusion injury. Furthermore, Homer1a knockdown promoted NF-κB P65Ser536 activation via caspase-8, NF-κB P65 nuclear translocation, NLRP3 inflammasome formation, and the production and processing of interleukin-1β and interleukin-18. The opposite results were observed with Homer1a overexpression. Finally, the combined administration of Homer1a protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1flox/ –/Homer1a+/ –/Nestin-Cre+/ – mice and apoptosis in Müller cells after ischemia/reperfusion injury. Taken together, these studies demonstrate that Homer1a exerts protective effects on retinal tissue and Müller cells via the caspase-8/NF-κB P65/NLRP3 pathway after I/R injury.

Changes in Inner Retina Thickness and Macular Sensitivity in Patients with Type 2 Diabetes with Moderate Diabetic Retinopathy.

The increase in diabetic retinopathy (DR) prevalence demonstrates the need for the determination of biomarkers for assessing disease development to obtain an early diagnosis and stop its progression. We aimed to analyse total retinal (RT) and inner retinal layer (IRL) thicknesses in type 2 diabetes mellitus (DM2) patients and correlate these results with retinal sensitivity using swept-source OCT (SS-OCT) and microperimetry. For this purpose, a total of 54 DM2 subjects with moderate diabetic retinopathy (DR) with no signs of diabetic macular oedema (DME) and 73 age-matched healthy individuals were assessed using SS-OCT to quantify retinal thickness in the nine macular areas of the ETDRS grid. Retinal sensitivity was measured via microperimetry with a Macular Integrity Assessment Device (MAIA). The mean ages were 64.06 ± 11.98 years for the DM2 group and 60.79 ± 8.62 years for the control group. DM2 patients presented lower visual acuity (p < 0.001) and a thicker RT (260.70 ± 19.22 μm in the control group vs. 271.90 ± 37.61 μm in the DM2 group, p = 0.01). The retinal nerve fibre layer (RNFL) was significantly lower in the outer nasal area (50.38 ± 8.20 μm vs. 45.17 ± 11.25 μm, p = 0.005) in ganglion cells and inner plexiform layers (GCL+) in DM2. A positive correlation between the LDL-C and RNFL and a negative correlation between HDL-C levels and the inner temporal and central RNFL thickness were detected. The central (p = 0.021) and inner nasal (p = 0.01) areas were negatively correlated between the RNFL and MAIA, while GCL++ was positively correlated with the outer inferior (p = 0.015) and outer nasal areas (p = 0.024). Retinal sensitivity and macular RNFL thickness decrease in DM2 patients with moderate DR with no DME, and this study enables an accurate approach to this disease with personalised assessment based on the DR course or stage. Thus, GCL+ and GCL++ thinning may support ganglion cell loss before the RNFL is affected.

Prph2 knock-in mice recapitulate human central areolar choroidal dystrophy retinal degeneration and exhibit aberrant synaptic remodeling and microglial activation.

Central areolar choroidal dystrophy is an inherited disorder characterized by progressive choriocapillaris atrophy and retinal degeneration and is usually associated with mutations in the PRPH2 gene. We aimed to generate and characterize a mouse model with the p.Arg195Leu mutation previously described in patients. Heterozygous (Prph2WT/KI) and homozygous (Prph2KI/KI) mice were generated using the CRISPR/Cas9 system to introduce the p.Arg195Leu mutation. Retinal function was assessed by electroretinography and optomotor tests at 1, 3, 6, 9, 12, and 20 months of age. The structural integrity of the retinas was evaluated at the same ages using optical coherence tomography. Immunofluorescence and transmission electron microscopy images of the retina were also analyzed. Genetic sequencing confirmed that both Prph2WT/KI and Prph2KI/KI mice presented the p.Arg195Leu mutation. A progressive loss of retinal function was found in both mutant groups, with significantly reduced visual acuity from 3 months of age in Prph2KI/KI mice and from 6 months of age in Prph2WT/KI mice. Decreased amplitudes in the electroretinography responses were observed from 1 month of age in Prph2KI/KI mice and from 6 months of age in Prph2WT/KI mice. Morphological analysis of the retinas correlated with functional findings, showing a progressive decrease in retinal thickness of mutant mice, with earlier and more severe changes in the homozygous mutant mice. We corroborated the alteration of the outer segment structure, and we found changes in the synaptic connectivity in the outer plexiform layer as well as gliosis and signs of microglial activation. The new Prph2WT/KI and Prph2KI/KI murine models show a pattern of retinal degeneration similar to that described in human patients with central areolar choroidal dystrophy and appear to be good models to study the mechanisms involved in the onset and progression of the disease, as well as to test the efficacy of new therapeutic strategies.

Optical coherence tomography angiography evaluation of optic disc and retinal vascular densities in obese patients

BackgroundTo evaluate optic disc and retinal vascular densities in obese patients using optical coherence tomography angiography (OCTA). MethodsThis study included 27 eyes from 27 obese patients with a body mass index (BMI) of ≥35 who were scheduled for bariatric surgery at the general surgery clinic and 26 eyes from 26 healthy individuals with a BMI of 18.5–24.9 kg/m2 who were of similar age and gender to the obese group. The macular vascular densities of the superficial and deep capillary plexuses (SCP and DCP, respectively), choriocapillaris flow area, optic disc peripapillary vascular density, and retinal thicknesses were evaluated using the OCTA device in obese patients and controls. ResultsThe mean age of the obese patients was 35.89 ± 10.93 years, and that of the controls was 32.31 ± 7.88 years (p = 0.199). The mean BMI values of the obese and control groups were 45.04 ± 6.89 kg/m2 and 23.19 ± 1.66 kg/m2, respectively (p < 0.0001). The whole, parafoveal, and perifoveal vascular density values of the SCP and those of the DCP were statistically significantly lower in the obese group than in the control group (p = 0.004, p = 0.011, p = 0.006, p = 0.036, p = 0.029, and p = 0.024, respectively). There was no significant difference between the two groups in terms of optic disc vascular density. Full retinal perifoveal thickness, full retinal perifoveal volume, inner retinal perifoveal thickness, and inner retinal perifoveal volume were statistically significantly lower in obese patients compared to the controls (p = 0.043, p = 0.042, p = 0.027, and p = 0.024, respectively). In addition, statistically significant negative correlations were found between BMI and the whole, parafoveal, and perifoveal vascular densities of the SCP and DCP and the whole vascular density values of the optic disc for all vessels and small vessels ​​(p = 0.017, r = -0.327; p = 0.043, r = -0.280; p = 0.033, r = -0.293; p = 0.034, r = -0.291; p = 0.017, r = -0.327; p = 0.023, r = -0.311; p = 0.031, r = -0.296; and p = 0.047, r = -0.274, respectively). ConclusionWe consider that the decrease in retinal vascular density and retinal thickness in obese patients is responsible for obesity-induced oxidative stress, increased inflammatory cytokines, and microvascular damage.

Comparative Efficacy, Durability and Safety of Faricimab in the Treatment of Diabetic Macular Edema: A Systematic Literature Review and Network Meta-Analysis.

A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice. An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible. Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55-125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4-4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92-1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations. Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab.

Состояние сетчатки у пациентов, перенесших COVID-19 с поражением легких

Microvascular lesions are one of the main factors of lung and other organ damage in COVID-19. We hypothesized that patients with post-COVID lung dysfunction may also retain signs of systemic micro-vascular damage, in particular of the retina. Aim. To evaluate vascular and macular retinal area status in COVID-19 patients with pulmonary damage. Methods. 61 patient, average age 60.5 years, after in-patient COVID-19 treatment was examined. The volume of lung lesions according to high resolution computed tomography (HRCT) data ranged from 12 to 90 %. Decrease of diffusion capacity for carbon monoxide (DLCO) was observed in all patients after recovery: in 3 months in 18 patients (29.5 %) with severe COVID-19 DLCO was 58.4 % and in moderate COVID-19 – 73.2 % of the proper one. Optical coherence tomography (iVue-100, Optovue, USA) using Linear Scan and Nerve Fiber 3D Disc map was performed after 1 and 3 months. The control group included 20 patients comparable by sex, age, and comorbidity. Results. All patients showed typical signs of micro-circulatory disturbances in the posterior pole of the eye, increased caliber of arteries and first-order veins. In patients with severe COVID-19 an increase of arterial caliber by 22.5 μm and veins caliber by 35.04 μm, a decrease of retinal thickness in the macular region (by 8.78 μm in the fovea and by 6.6 μm in parafovea) compared to control group were revealed. After 6 months no significant dynamics of these parameters was revealed. Retinal changes in patients with moderate COVID-19 were similar but less pronounced. Conclusion.The revealed changes of retinal vessels and macular zone may indicate microcirculation disturbances and blood flow retardation in the posterior pole of the eye. The severity of the disturbances is comparable with the severity of the disease and the degree of DLCO reduction. Key words: COVID-19 with lung damage; retina; caliber of retinal vessels.

Nonhuman Primate Eyes Display Variable Growth and Aging Rates in Alignment With Human Eyes.

To assess age-related biometric changes of the eye in nonhuman primates (NHPs), to and decipher the growth and aging rates and their comparability with humans. Ocular anatomic measurements were performed on 341 macaca fascicularis aged 0.5 to 23 years via multimodal approaches including IOLMaster 700. Linear or polynomial regression models were simulated to determine the best fitted age-related function. The metrics were compared with human equivalents in published reports. Macaques exhibited a postnatal eye growth pattern similar to humans, characterized by continuous eye extension coordinated with dramatic reshaping of the lens but not the cornea. The age-related growth of lens thickness (LT), anterior chamber depth (ACD), and axis length (AL) exhibited nonlinear and bipolar patterns. The inflection points were 10 to 12 years old for LT and ACD and 13 to 15 years old for AL in macaques, which were comparable in chronological age at a ratio of ∼1: ratio with that in humans. In contrast, the speed of aging, including the increase in lens density and the decrease in retinal nerve fiber layer thickness, was comparable in relative age at a ratio of ∼1:3 according to the differences in lifespan between macaques and humans. Lens density was a robust indicator for the aging process. Macaque eyes recapitulated the age-related process of human eyes to varying extents with different growth and aging rates. Chronological age or relative age should be considered in different scenarios when macaques are included in preclinical studies.

Intravitreal Brolucizumab and Aflibercept for Polypoidal Choroidal Vasculopathy.

Purpose: To compare the effectiveness of intravitreal injections of brolucizumab and aflibercept in patients with polypoidal choroidal vasculopathy (PCV). Methods: In total, 62 treatment-naive PCV eyes (62 patients) treated with intravitreal brolucizumab or aflibercept were analyzed retrospectively. All patients received a monthly loading injection of antivascular endothelial growth factor for 3 months, followed by further injections as required. Visual and anatomical outcomes were compared between drugs after 12 months of treatment. Results: The improvement in best-corrected visual acuity after 12 months of treatment was not significantly different between the brolucizumab-treated (22 eyes) and aflibercept-treated groups (40 eyes). However, in the brolucizumab-treated group, there was a significantly greater decrease in central retinal thickness (172 vs. 147 μm; P = 0.031) and subfoveal choroidal thickness after treatment (51 vs. 29 μm; P = 0.025). In addition, the regression rate of polypoidal lesions was significantly higher in the brolucizumab-treated group (77.3%, 17/22 eyes) than that in the aflibercept-treated group (45.0%, 18/40 eyes; P = 0.014). Sterile intraocular inflammation showing mild vitritis was observed in 1 of the 22 eyes (4.5%) of brolucizumab-treated patients. Conclusion: Intravitreal brolucizumab injections for PCV showed visual improvement comparable to that of aflibercept during the 12-month treatment period. However, brolucizumab was more effective than aflibercept for the regression of polypoidal lesions and caused a greater decrease in central retinal thickness and subfoveal choroidal thickness.

Development of a rabbit model of Adenosine triphosphate-induced monocular retinal degeneration for optimization of retinal prostheses.

Optimization of retinal prostheses requires preclinical animal models that mimic features of human retinal disease, have appropriate eye sizes to accommodate implantable arrays, and provide options for unilateral degeneration so as to enable a contralateral, within-animal control eye. In absence of a suitable non-human primate model and shortcomings of our previous feline model generated through intravitreal injections of Adenosine Triphosphate (ATP), we aimed in the present study to develop an ATP induced degeneration model in the rabbit. Six normally sighted Dutch rabbits were monocularly blinded with this technique. Subsequent retinal degeneration was assessed with optical coherence tomography, electroretinography, and histological assays. Overall, there was a 42% and 26% reduction in a-wave and oscillatory potential amplitudes in the electroretinograms respectively, along with a global decrease in retinal thickness, with increased variability. Qualitative inspection also revealed that there were variable levels of retinal degeneration and remodeling both within and between treated eyes, mimicking the disease heterogeneity observed in retinitis pigmentosa. These findings confirm that ATP can be utilized to unilaterally induce blinding in rabbits and, potentially present an ideal model for future cortical recording experiments aimed at optimizing vision restoration strategies.Clinical Relevance- A rapid, unilaterally induced model of retinal degeneration in an animal with low binocular overlap and large eyes will allow for clinically valid recordings of downstream cortical activity following retinal stimulation. Such a model would be highly beneficial for the optimization of clinically appropriate vision restoration approaches.