Areas Of Retinal Nonperfusion Research Articles

Nonperfusion of the Far Peripheral Retina in Highly Myopic Stickler Syndrome.

Purpose: To describe the clinical course of 3 patients with Stickler syndrome found on fluorescein angiography (FA) to have nonperfusion of the peripheral retina. Methods: Three patients with confirmed Stickler syndrome were examined under anesthesia. Genetic testing and FA were performed. Results: Each patient had characteristic ocular findings of Stickler syndrome, including high myopia with vitreoretinal degeneration. FA was performed on each patient and showed 360 degrees of nonperfusion of the retinal periphery in all eyes, with mild leakage in Case 3. Conclusions: The current series presents evidence of peripheral retinal nonperfusion in 3 consecutive patients with Stickler syndrome. Based on these findings, the authors recommend adopting FA as a standard imaging modality and using laser photocoagulation to treat the areas of retinal nonperfusion for all patients with Stickler syndrome.

Apoptotic Vesicles Modulate Endothelial Metabolism and Ameliorate Ischemic Retinopathy via PD1/PDL1 Axis.

Pathological angiogenesis with subsequent disturbed microvascular remodeling is a major cause of irreversible blindness in a number of ischemic retinal diseases. The current anti-vascular endothelial growth factor therapy can effectively inhibit angiogenesis, but it also brings significant side effects. The emergence of stem cell derived extracellular vesicles provides a new underlining strategy for ischemic retinopathy. Apoptotic vesicles (apoVs) are extracted from stem cells from human exfoliated deciduous teeth (SHED). SHED-apoVs are delivered into the eyeballs of oxygen-induced retinopathy (a most common model of angiogenic retinal dieseases) mice through intravitreal injection. The retinal neovascularization and nonperfusion area, vascular structure, and density changes are observed during the neovascularization phase (P17) and vascular remodeling phase (P21), and visual function is measured. The expression of extracellular acidification rate and lactic acid testing are used to detect endothelial cells (ECs) glycolytic activity. Furthermore, lentivirus and neutralizing antibody are used to block PD1-PDL1 axis, investigating the effects of SHED-apoVs on glycolysis and angiogenic activities. This work shows that SHED-apoVs are taken up by ECs and modulate the ECs glycolysis, leading to the decrease of abnormal neovessels and vascular remodeling. Furthermore, it is found that, at the molecular level, apoVs-carried PD1 interacts with PDL1 on hypoxic ECs to regulate the angiogenic activation. SHED-apoVs inhibit pathological angiogenesis and promote vascular remodeling in ischemic retinopathy partially by modulating ECs glycolysis through PD1/PDL1 axis. This study provides a new potential strategy for the clinical treatment of pathological retinal neovascularization.

The correlation of folic acid and homocysteine serum with vascular density and retinal non-perfusion area in diabetic retinopathy

Background : Diabetic Retinopathy (DR) is the most common microvascular complication of Diabetes Mellitus (DM). Homocysteine has been studied as a biomarker in DR, while folic acid exhibits anti-proliferative effects in DR.
 Objective : To analyze the correlation between folic acid and homocysteine serum with vascular density and retinal non-perfusion area in healthy individuals and patients with diabetic retinopathy.
 Methods : This is an observational study with a cross-sectional design, conducted in Dr. Kariadi Hospital and GAKI laboratory in Semarang in January 2023. This study included 60 samples: 15 healthy individuals, 15 patients with DM but no DR, 15 patients with Non-Proliferative Diabetic Retinopathy (NPDR), and 15 patients with Proliferative Diabetic Retinopathy (PDR). Patients were examined for serum folic acid and homocysteine using blood laboratory tests, vessel density and retinal non-perfusion areas using optical coherence tomography angiography (OCTA).
 Results : There was a negative correlation with weak strength between folic acid levels and retinal non-perfusion area of the retina in all samples (Folic acid levels vs retinal non-perfusion area, p = 0.009, Spearman correlation = -0.335). There was a positive correlation with weak strength between folic acid levels and vascular density in all samples (Folic acid levels vs vascular density, p = 0.009, Spearman correlation = 0.337). There was a positive correlation with moderate strength between homocysteine levels and retinal non-perfusion area in all samples (Homocysteine levels vs non–perfusion area of the retina, p = 0.001, Spearman correlation = 0.426). There was a positive correlation with moderate strength between homocysteine levels and vascular density in all samples (Homocysteine levels vs vascular density, p = 0.001, Spearman correlation = -0.414).
 Conclusion : There was a correlation between folic acid and homocysteine serum with vascular density and retinal non-perfusion areas.

Optical coherence tomography angiography macular biomarkers of peripheral retinal ischemia in diabetic macular edema: secondary endpoints from the clinical study "FOVEA".

To investigate the relationship between the macular values of fractal dimension (FD) and lacunarity (LAC) on optical coherence tomography angiography (OCTA) images and the presence of peripheral retina non-perfusion areas (NPAs) on fluorescein angiography (FA) in patients with treatment-naïve diabetic macular edema (DME). Fifty patients with treatment-naïve DME underwent a full ophthalmic examination, including best-corrected visual acuity measurement, FA, spectral-domain optical coherence tomography, and OCTA. Specifically, FA was performed to detect the presence of retinal NPAs, whereas fractal OCTA analysis was used to determine macular FD and LAC values at the level of thesuperficial and deep capillary plexus (SCP and DCP). FA montage frames of the posterior pole and peripheral retina, as well as macular OCTA slabs of the SCP and DCP, were obtained. Thirty (60%) eyes with FA evidence of peripheral retinal NPAs in at least one quadrant showed significantly lower FD and higher LAC in both SCP and DCP, when compared with eyes presenting a well-perfused peripheral retina. Furthermore, macular FD and LAC values were found to be significantly associated with the extent of retinal NPAs. Macular FD and LAC of both SCP and DCP seem to be strongly associated with the extent of peripheral retinal NPAs, thus suggesting that may be useful predictive biomarkers of peripheral ischemia in treatment-naïve DME eyes.

Ocular and Systemic Risk Factors for Disease Worsening Among Patients with NPDR: Post Hoc Analysis of the PANORAMA Trial

PurposeIdentify baseline systemic and ocular characteristics associated with nonproliferative diabetic retinopathy (NPDR) worsening, and the impact of intravitreal aflibercept injection (IAI) on these associations. DesignPost hoc analysis of PANORAMA. ParticipantsPatients with moderately severe to severe NPDR enrolled in the prospective PANORAMA phase 3 trial. MethodsAssociations between baseline systemic and ocular factors with events indicative of NPDR worsening at Week 100 were evaluated by multivariable analysis in sham-treated eyes. NPDR worsening was defined as development of (1) vision-threatening complications (VTCs; comprising PDR and/or anterior segment neovascularization), (2) center-involved diabetic macular edema (CI-DME), or (3) ≥ 2-step Diabetic Retinopathy Severity Scale (DRSS) worsening. Impact of IAI on identified baseline factors was evaluated using univariable analysis in combined IAI groups. Main Outcomes MeasuresBaseline systemic and ocular factors associated with events indicative of NPDR worsening at Week 100. The cumulative incidence and risk of developing such events at Week 100 among sham versus IAI-treated eyes. ResultsUsing multivariable analyses among sham-treated eyes, 5 baseline factors associated with increased risk of NPDR worsening were identified: fluorescein leakage, retinal nonperfusion area, thicker central subfield thickness, eosinophil level, and proteinuria. Considering baseline fluorescein leakage area as a prognostic indicator in detail, the risk of developing VTCs alone, VTCs and/or CI-DME, or ≥ 2-step DRSS worsening increased with increasing fluorescein leakage area in the sham group (all P < 0.05). Considering baseline retinal nonperfusion area as a prognostic indicator in detail, the risk of developing VTCs alone, CI-DME alone, or VTCs and/or CI-DME increased with increasing baseline retinal nonperfusion area in the sham group (all P < 0.05). In contrast, among IAI-treated eyes, increasing baseline fluorescein leakage or retinal nonperfusion areas did not increase the risks of NPDR worsening. ConclusionsWithin the PANORAMA trial, increased areas of fluorescein leakage and retinal nonperfusion at baseline were identified as key ocular biomarkers associated with events indicative of NPDR worsening among sham-treated patients. IAI treatment appeared to mitigate the effect of these baseline risk factors and reduced the likelihood of NPDR worsening.

A new phenotype or retinal involvement in Steinert Disease: a case report.

To report a case illustrating the association of Steinert Disease (SD) with peripheral retinal non-perfusion areas and epiretinal membrane. Case report. A 47-year-old Caucasian female diagnosed with SD was referred for blurred vision in her right eye (RE). She presented bilateral ptosis with deficit of elevator muscle.Dilated fundus examination revealed altered macular reflex, peripheral vascular alterations, and ghost vessels bilaterally. Structural spectral domain optical coherence tomography (SD-OCT) showed an epiretinal membrane with a partial alteration of the foveal profile in the RE. Optical coherence tomography angiography (OCTA) images revealed no evidence of neovascular membrane in the macular region. Fluoresceine angiography (FA) showed retinal peripheral non perfusion areas and leakage in the late phases of the examination. Any retinal alteration should be considered during the ophthalmological examination of patients suffering from type 1 myotonic dystrophy. OCT and fluoresceine angiography should be performed evaluating the SD patient that complains about visual impairment.

PREDICTION OF DIABETIC RETINOPATHY SEVERITY USING A COMBINATION OF RETINAL NEURODEGENERATION AND CAPILLARY NONPERFUSION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To generate a prediction model of diabetic retinopathy (DR) severity stages based on retinal neurodegeneration and capillary nonperfusion area (NPA) detected using optical coherence tomography (OCT) and OCT angiography (OCTA). A total of 155 treatment-naïve eyes were retrospectively included. Macular ganglion cell/inner plexiform layer (mGCIPL) thickness in six macular regions was measured. A custom algorithm was used to calculate capillary NPA from 3 × 3 mm 2 and 12 × 12 mm 2 field OCTA images. The region of interest was selected as circular areas of 3 mm and 12 mm diameter and divided into six subsections. Classification and regression tree analysis identified the best predictors to discriminate between the five DR stages. Inferotemporal sector showed the largest mean NPA, and the inferior hemispheric NPA was significantly larger compared with the superior hemisphere. The mean mGCIPL thickness was significantly correlated with NPA of 12 × 12 mm 2 field in participants with early stage DR. Inferior hemispheric NPA of 12 × 12 mm 2 field and mean mGCIPL thickness were the two best variables to discriminate no DR versus mild nonproliferative DR (NPDR) and mild versus moderate NPDR (accuracy: 88.8% and 93.5%). Meanwhile, a combination of NPA of 12 × 12 mm 2 and 3 × 3 mm 2 fields was the best prediction model to discriminate moderate versus severe NPDR and severe NPDR versus PDR (accuracy: 91.8% and 94.1%). A combination model of capillary NPA and mGCIPL thickness may be a novel biomarker for predicting DR severity. Capillary nonperfusion seems to initially occur in the midperipheral retina with macular neurodegeneration and progress posteriorly.

Оценка макулярного кровотока с помощью оптической когерентной томографии-ангиографии у беременных женщин, страдающих сахарным диабетом

Purpose. To study retinal blood flow in pregnant women with disorders of carbohydrate metabolism using optical coherence tomography angiography (OCTA) in order to determine the criteria for the manifestation and progression of diabetic retinopathy (DR). Material and methods. 203 pregnant women in the third trimester were examined: 24 – with type 1 and 2 diabetes (T1D and T2D), 143 – with gestational diabetes (GD), and 36 apparently healthy women with physiological pregnancy, who consisted the control group. OCTA imaging was performed using the RTVue XR Avanti OCT 6 mm × 6 mm «Angio Retina» scan protocols (Optovue, USA). The whole image vessel density (wiVD), foveal vessel density (FVD), and foveal avascular zone (FAZ) area in the superficial capillary plexus were studied. Results. FVD in pregnant women with diabetes was significantly less than in pregnant women with GD and in the control group. In this connection, it can be assume changes of the retinal microvascular regulation, due to chronic disorders of carbohydrate metabolism in patients with diabetes, and development of microangiopathy. Enlargement of FAZ area and decrease of wiVD were revealed in patients with DR, relative to datas obtained in the group of pregnant women with diabetes and absence of DR, in the absence of differences in FVD indexes. In 2 patients with T1D and the absence of ophthalmoscopic signs of DR, OCTA revealed areas of nonperfusion in the posterior pole of the eye. Conclusion. OCTA helps to identify areas of retinal nonperfusion in the posterior pole of the eye in pregnant women with diabetes in the absence of ophthalmoscopic signs of DR and allows determining objective indications for timely retinal laser coagulation. Keywords: optical coherence tomography angiography, pregnancy, diabetic retinopathy, gestational diabetes, foveal avascular zone, retinal blood flow

Результаты изучения ретинального кровотока у беременных с сахарным диабетом с помощью оптической когерентной томографии-ангиографии

Purpose. To study retinal blood flow in pregnant women with disorders of carbohydrate metabolism using optical coherence tomography angiography (OCTA). Material and methods. 203 pregnant women in the third trimester of pregnancy were examined: 24 — with type 1 and 2 diabetes (T1D and T2D), 143 — with gestational diabetes (GD), and 36 healthy women with physiological pregnancy, who consisted the control group. OCTA imaging was performed using the RTVue XR Avanti OCT 6 mm × 6 mm «Angio Retina» scan protocols (Optovue, USA). The vascular density (VD), vascular density in the fovea (VDF), and foveal avascular zone (FAZ) area in the superficial capillary plexus were studied. Results. Among studied patients no significant differences in VD and in FAZ area were found. VDF in pregnant women with diabetes was significantly less than in pregnant women with GD and in the control group. There were no significant differences in the studied parameters in groups with different periods of GD manifestation. In pregnant women with diabetes with presence and absence of DR, retinal blood flow did not differ significantly. Given the absence of differences of studied parameters in pregnant women with diabetes without DR and with DR, it can be assumed that the retinal microvascular regulation changes due to chronic disorders of carbohydrate metabolism in patients with diabetes and the development of microangiopathy. In 2 patients with T1D and the absence of ophthalmoscopic signs of DR, OCTA revealed areas of nonperfusion in the posterior pole of the eye. Conclusion. OCTA helps to identify areas of retinal nonperfusion in the posterior pole of the eye in pregnant women with diabetes in the absence of ophthalmoscopic signs of DR. Keywords: optical coherence tomography angiography, pregnancy, diabetic retinopathy, retinal blood flow

Clinical features of retinal amyloid angiopathy with transthyretin Gly83Arg variant.

To report on the clinical features of patients with retinal amyloid angiopathy (RAA) who were identified to be caused by the transthyretin (TTR) Gly83Arg variant. Case series of five patients diagnosed with RAA was collected at Affiliated Hospital of Zunyi Medical University from January 2010 to December 2021. The clinical features, therapeutic strategies, and prognoses of all patients were reviewed. Five patients with a mean age of 52.00±7.23y were diagnosed as RAA. These patients were previously diagnosed with hereditary transthyretin amyloidosis caused by the TTR Gly83Arg variant. Vitreous opacity was found in all 10 eyes, and 7 eyes developed RAA 2 to 20y after the onset of hereditary transthyretin amyloidosis. The clinical manifestations were recurrent vitreous hemorrhage in 2 eyes (29%), neovascular glaucoma in 2 eyes (29%), and iris neovascularization in 1 eye (14%). Microangioma lesions were found in all affected eyes that underwent fundus fluorescein angiography (FFA) in this group of cases, and the incidence of the retinal non-perfusion area was 67%. Although no cases of retinal neovascularization were found, the prognosis of visual acuity was not ideal. This is the first report of RAA in patients with the TTR Gly83Arg variant. Complications such as RAA and glaucoma will seriously affect the visual prognosis of patients. Thereafter, regular ophthalmic follow-up of patients with hereditary transthyretin amyloidosis is essential. And FFA after vitrectomy is very important, which can help ophthalmologists detect RAA earlier and treat it in time.

Neuroprotective Effects of Human Adipose-Derived Mesenchymal Stem Cells in Oxygen-Induced Retinopathy.

This study was designed to provide evidence of the neuroprotective of human adipose-derived mesenchymal stem cells (hADSCs) in oxygen-induced retinopathy (OIR). In vivo, hADSCs were intravitreally injected into OIR mice. Various assessments, including HE (histological evaluation), TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, electroretinogram (ERG) analysis, and retinal flat-mount examination, were performed separately at postnatal days 15 (P15) and 17 (P17) to evaluate neurological damage and functional changes. Western blot analysis of ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF) was conducted at P17 to elucidate the neuroprotective mechanism. The P17 OIR group exhibited a significant increase in vascular endothelial cell nuclei and neovascularization that breached the ILM (inner limiting membrane) to the P17 control group. In addition, the retinal nonperfusion areas in the P17 OIR group and the number of apoptotic retinal cells in the P15 OIR group were significantly higher than in the corresponding hADSCs treatment group and control group. There was no significant thickness change in the inner nuclear layer (INL) but the outer nuclear layer (ONL) in the P17 OIR treatment group compared with the P17 OIR group. The cell density in the INL and ONL at P17 in the hADSCs treatment group was not significantly different from the OIR group. The amplitude of a-wave and b-wave in scotopic ERG analysis for the P17 OIR group was significantly lower than in the P17 hADSCs treatment group and the P17 control group. Furthermore, the latency of the a-wave and b-wave in the P17 OIR group was significantly longer than in the P17 hADSCs treatment group and the P17 control group. In addition, the expression levels of CNTF and BDNF in the P17 OIR group were statistically higher than those in the P17 control group, whereas the expression of GDNF was statistically lower in the P17 OIR group, compared with the P17 control group. The expression of CNTF and GDNF in the P17 hADSCs treatment group was statistically higher than in the P17 OIR group. However, the expression of BDNF in the P17 hADSCs treatment group was statistically lower than in the P17 OIR group. This study provides evidence for the neuroprotective effects of hADSCs in OIR.

Retinal haemorrhages on ultra-widefield red channel images and perfusion status in central retinal vein occlusion.

To evaluate the relationship between retinal haemorrhages detected on Ultra-widefield (UWF) red channel images and perfusion status in eyes with acute central retinal vein occlusion (CRVO). UWF fundus images were split into green and red channels using ImageJ software. The retinal haemorrhages were calculated quantitatively with both the green and red channel images, resulting in green channel haemorrhages (GCH) and red channel haemorrhages (RCH). The nonperfusion area (NPA) was also calculated from fluorescein angiography in each eye. The relationships between both the GCH and RCH with the NPA were investigated. Thirty-two eyes of 32 patients with acute CRVO (18 men, 14 women) were included. The mean GCH and RCH values were 10.4% ± 8.2% and 1.7% ± 1.7%, respectively. The mean NPA was 39.2% ± 28.8%. Significant correlations were seen between the GCH and NPA (r = 0.38; P = 0.022) and RCH and NPA (r = 0.44; P = 0.010, linear regression analysis). Multivariate analysis suggested that only the RCHs were correlated significantly with the NPA. Retinal haemorrhages detected by UWF red channel imaging were less compared to green channel imaging and associated closely with retinal NPAs in eyes with acute CRVO. UWF red channel imaging allowed us to identify ischaemia-related haemorrhage.

Values of optical coherence tomography angiography for diagnosing diabetic retinopathy and evaluating treatment outcomes

To compare the consistency between fundus fluorescein angiography (FFA) and optical coherence tomography angiography (OCTA) for the diagnosis of diabetic retinopathy (DR). Ninety-six diabetic patients (185 eyes) treated from January 2019 to December 2019 underwent OCTA and FFA. The image characteristics of fundus lesions were recorded. Sixty-nine patients (137 eyes) who were diagnosed with DR by both examinations and needed to receive panretinal photocoagulation (PRP) were selected. The retinal nerve fiber layer (RNFL) thickness, macular superficial vascular complex (SVC) and deep vascular complex (DVC) blood flow density, 300μm area surrounding foveal avascular zone (FAZ) (FD300) blood flow density and FAZ parameters were compared. The Kappa coefficient of FFA and OCTA for diagnosing DR was 0.537 (P=0.000). FFA and OCTA had substantial consistency for detecting retinal microaneurysms and macular edema (Kappa coefficient=0.643/0.616, P=0.000), perfect consistency for detecting retinal neovascularization and retinal non-perfusion area (Kappa coefficient=0.809/0.832, P=0.000), and moderate consistency for detecting structural changes in the macular ring (Kappa coefficient=0.423, P=0.000). The RNFL thickness in the peripapillary and the superior temporal, temporal inferior, inferior nasal and superior nasal regions rose 1 week after PRP but declined 1 year after treatment (P<0.05). The macular SVC, DVC and FD300 blood flow density declined 1 week after PRP but rose 1 year after treatment (P<0.05). OCTA shows consistency with FFA for diagnosing DR, which remedies the deficiency of FFA. The reduction in fundus lesions after PRP can be quantified by OCTA.

Expression of the neuroprotective factors BDNF, CNTF, and FGF-2 in normal and oxygen induced retinopathy.

Oxygen-induced retinopathy is a type of retinal pathological neovascularization (NV) disease that leads to vision loss and translates to a significant societal cost. Anti-vascular endothelial growth factor (VEGF) and anti-inflammatory treatments have been widely used in the clinic, but the results have not been entirely satisfactory. It is necessary to explore other treatments for Ischemic retinal diseases. The oxygen-induced retinopathy (OIR) model was induced from P7 to P12 as described. Histology evaluation (HE) and retina flat mounts were checked at P17 to confirm the establishment of the OIR model. Retinal ganglion cell (RGC) degeneration was checked by transmission electron microscopy at P17 to confirm the neurological damage caused by OIR. Western blot analysis was performed at P12, P15, and P17 to study the expression of brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and fibroblast growth factor 2 (FGF-2) in normal and OIR mice. Comparative analysis of the expressions of BDNF, CNTF, and FGF-2 in normal and OIR mice was performed. There were many retinal NV and non-perfusion areas in OIR P17. RGCs were degenerated at OIR P17. The expressions of BDNF, CNTF, and FGF-2 gradually increased from P12 to P17 in normal mice and were much higher in OIR mice. The expression curves of BDNF, CNTF, and FGF-2 in the OIR model were inconsistent and did not correlate with each other. This study provides evidence for changes in BDNF, CNTF, and FGF-2 in Oxygen-induced retinopathy.

Correlation analysis between foveal avascular zone and near peripheral retinal hypoperfusion in multiple sclerosis: a wide field optical coherence tomography angiography study.

The identification of non-invasive biomarkers to investigate and monitor retinal structural and vascular changes in multiple sclerosis (MS) represents an interesting source of debate. Until now optical coherence tomography angiography (OCTA) evaluated the foveal avascular zone (FAZ) and areas of retinal non-perfusion only in the macular region in MS patients. It could be interesting to identify possible biomarkers, useful in assessing the ischemic areas also in the near peripheral retina, since FAZ enlargement and the areas of peripheral retinal non-perfusions share common pathogenic processes. In this cross-sectional study, we investigated the correlation between the FAZ area and retinal vessel density (VD) in the near peripheral retina by new wide-field optical coherence tomography angiography (OCTA) in patients affected by relapsing-remitting multiple sclerosis (RR-MS). Moreover, we compared the FAZ area and the VD of superficial and deep capillary plexuses in the fovea region and in the near peripheral retina (6.4 × 6.4 mm) between RR-MS patients and healthy controls by means of a Solix full-range OCTA. Last, we also detected the changes in structural OCT parameters (ganglion cell complex and retinal nerve fiber layer). Thirty-three eyes of 33 RR-MS patients and 35 eyes of 35 healthy controls were enrolled. RR-MS patients showed a lower VD in the superficial capillary plexus and a significant increase in the FAZ area compared with controls. The deep capillary plexus revealed a reduced VD although not statistically significant in patients with respect to controls. In the patients' group, the FAZ area showed significantly negative correlations with VD of superficial capillary plexuses in the foveal and whole region, while the FAZ area did not negatively correlate with the VD of the deep capillary plexus. The significant correlations among OCTA parameters could demonstrate the FAZ area as a possible biomarker for assessing the perfusion status in the near peripheral retina, useful in RR-MS management. These findings could confirm the role of vascular dysfunction in the pathogenetic mechanisms of MS.

Preretinal Microvascular Tufts Associated with Dyskeratosis Congenita

A 16-year-old boy with dyskeratosis congenita (DC), a very rare polymorphous inherited telomeropathy, was referred for bilateral large peripheral temporal areas of retinal nonperfusion (Fig A). Absence of associated retinal neovascularization was confirmed by fluorescein angiography (FA) (Fig B). Although peripheral retinal ischemia is known in DC, unexpected numerous reddish, rounded, preretinal microvascular tufts were also observed in the inferonasal macula. They were distinct on the near-infrared image (Fig C) and localized above the retinal surface on OCT B-scans (Fig D).

Impact of Intravitreal Anti-VEGF Therapy on Microperimetry of the Retinal Nonperfusion Areas of Patients with Proliferative Diabetic Retinopathy.

This study assessed retinal nonperfusion area (NPA) changes after anti-VEGF treatment in proliferative diabetic retinopathy (PDR) eyes using swept-source widefield optical coherence tomography angiography (SS-WFOCTA) and investigated the relationships with the microperimetry (MP-1) functional changes observed in the same areas. This was a single-center observational case series. Seven PDR eyes naïve to treatment that received three monthly intravitreal injections of aflibercept were included. All eyes were imaged with SS-WFOCTA and MP-1 at baseline (T0) and 1month after the third injection (T1). The regions of interest (ROIs) with evidence of NPAs at T0 OCTA images were selected. Qualitative and quantitative [perfusion density (PD) and vessel length density (VLD)] OCTA vascular changes in the selected ROIs between T0 and T1 were compared with the corresponding MP-1 functional changes [mean sensitivity (MS)]. Twenty-five ROIs were selected. In 52% of the ROIs, an improvement in MS was observed at T1, which was associated with qualitative and quantitative improvement in 92.3% of NPAs by OCTA. In 32% of the ROIs, MS worsening was observed at T1, which was associated with qualitative and quantitative worsening in 75% of NPAs by OCTA. Positive correlations between MS and both PD and VLD were found. Fisher's test showed an association between the improvements in MP and VLD. An association between OCTA and MP-1 parameter changes was found. The concomitant functional and morphological improvement in half of the ROIs suggests that anti-VEGF treatment may promote retinal changes that result in a better functional response.

Major clinical findings of cellular therapy for intravitreal use in ischemic retinopathy and macular degeneration: a systematic review

Introduction: In the scenario of eye diseases, diabetic retinopathy and retinal vein occlusion are the two most common ischemic retinopathies in the world. Ischemia is caused by retinal vascular diseases due to decreased blood perfusion and the appearance of areas of retinal non-perfusion. Also, age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in people over 65 years of age in industrialized countries. By 2020, around 200 million people will be affected by AMD worldwide. Objective: the present systematic review study aimed to highlight the main clinical findings of the treatment of ischemic retinopathy and age-related macular degeneration through cell therapy with bone marrow stem cells. Methods: The rules of the Systematic Review-PRISMA Platform were followed. The search was carried out from March 2022 to June 2022 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument. The risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: It was found 235 articles involving retinitis pigmentosa, macular degeneration, and bone marrow stem cell therapy. A total of 51 were fully evaluated and 28 studies were included and developed in a systematic review in the results field. The symmetrical Funnel Plot does not suggest a risk of bias between the small sample size studies. It was concluded that intravitreal injection of bone marrow-derived stem cells in a patient with retinal vascular occlusion sequelae demonstrated that the procedure is feasible and safe to be performed in humans as there were no signs of infection, inflammation, or development of intraocular tumor formation. Also, neurotrophic effects correlate with vasculature preservation, suggesting that bone marrow-derived stem cells can be used in the treatment of diseases such as retinal degenerations and vasculopathy that currently lack effective treatment. The authors concluded that stem cells can protect retinal cells from degeneration and also suggested that they were able to replace some types of lost retinal neurons.

Atypical Adams-Oliver syndrome with typical ocular signs of familial exudative vitreoretinopathy

AIM: To report an atypical Adams-Oliver syndrome (AOS) family with typical ocular signs of familial exudative vitreoretinopathy (FEVR). METHODS: A patient with visible avascular area and obvious non-perfusion zone in the peripheral retina with systemic signs of AOS was reported. Familial and personal characteristics were collected for the patient and his sister. Gene sequencing and ophthalmic examinations including fluorescein angiography were all performed for the whole family. RESULTS: Two novel mutations of DOCK6 (c.1396C&gt;T and c.4796G&gt;A) were identified in the proband and his family, and two compound heterozygous mutations were revealed in the proband and his sister. The patient and his sister showed physical deformities and mental abnormalities while FEVR mimicking retinal disorder can also be defined. No remarkable ocular or systemic abnormality can be observed for their parents. Peripheral retinal non-perfusion area, obvious abnormal vascularization or even retinal fold were observed in the proband and his sister, while only small avascular zone was identified for their parents. CONCLUSION: This is the first genetic authenticated AOS case mimicked as FEVR with genetic sequencing of a family. For the patients with ocular phenotype of FEVR, further examination should be performed if the systemic or mental abnormalities exist.

Microvascular Changes in the Cystic Lesion of Branch Retinal Vein Occlusion Imaged by Swept-Source Optical Coherence Tomography Angiography

Introduction: This study aimed to describe the quantitative features of the microvasculature in the cystic lesions of branch retinal vein occlusion (BRVO). Methods: A total of 43 eyes with BRVO, treated with anti-vascular endothelial growth factor therapy, were analyzed. Using wide-field swept-source optical coherence tomography angiography (OCTA), en face OCT images were obtained by depth-integrated reflectivity of the retina, and vascular density (VD), vascular length (VL), vascular lacunarity, and fractal dimension (FD) were evaluated in a 12 × 12-mm area of retinal nonperfusion. Results: The mean area of affected lesions was 38.7 ± 19.8 mm², and cystic lesions were 8.5 ± 10.1 mm². VD, VL, and FD were significantly decreased in the cystic lesions compared to other affected lesions in the same eyes (p = 0.0010, p = 0.0001, and p = 0.0003, respectively) and in all eyes (p = 0.0281, p = 0.0050, and p < 0.0001, respectively). VD in cystic lesions within the vascular arcade (25 eyes) correlated with best-corrected visual acuity on OCTA (r = −0.433, and p = 0.0492). Conclusions: Vascular structure in the cystic lesions was unpreserved compared to the other lesions in BRVO. These findings may help in understanding the pathophysiology of retinal edema in BRVO.