Retinal Vascularization Research Articles

Lrp5 p.Val667Met Variant Compromises Bone Mineral Density and Matrix Properties in Osteoporosis.

Early-onset osteoporosis (EOOP) has been associated with several genes, including LRP5, coding for a coreceptor in the Wnt pathway. Variants in LRP5 were also described in osteoporosis pseudoglioma syndrome, combining severe osteoporosis and eye abnormalities. Genomewide-association studies (GWAS) showed that LRP5 p.Val667Met (V667M) variant is associated with low bone mineral density (BMD) and increased fractures. However, despite association with a bone phenotype in humans and knockout mice, the impact of the variant in bone and eye remains to be investigated. Here, we aimed to evaluate the bone and ocular impact of the V667M variant. We recruited 11 patients carrying the V667M variant or other loss-of-function variants of LRP5 and generated an Lrp5 V667M mutated mice. Patients had low lumbar and hip BMD Z-score and altered bone microarchitecture evaluated by HR-pQCT compared with an age-matched reference population. Murine primary osteoblasts from Lrp5 V667M mice showed lower differentiation capacity, alkaline phosphatase activity, and mineralization capacity in vitro. Ex vivo, mRNA expression of Osx, Col1, and osteocalcin was lower in Lrp5 V667M bones than controls (all p < 0.01). Lrp5 V667M 3-month-old mice, compared with control (CTL) mice, had decreased BMD at the femur (p < 0.01) and lumbar spine (p < 0.01) with normal microarchitecture and bone biomarkers. However, Lrp5 V667M mice revealed a trend toward a lower femoral and vertebral stiffness (p = 0.14) and had a lower hydroxyproline/proline ratio compared with CTL, (p = 0.01), showing altered composition and quality of the bone matrix. Finally, higher tortuosity of retinal vessels was found in the Lrp5 V667M mice and unspecific vascular tortuosity in two patients only. In conclusion, Lrp5 V667M variant is associated with low BMD and impaired bone matrix quality. Retinal vascularization abnormalities were observed in mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Short Term Effects of Anti-VEGF Agents on Retinal Vascularity

Bu çalışmada, retinal vasküler hastalıklara ve yaşa bağlı makula dejenerasyonuna ikincil gelişen maküla ödeminin tedavisi için anti-vasküler endotelyal büyüme faktörü (VEGF) enjeksiyonu uygulanan hastalarda akut dönemde optik koherens tomografi (OCT) ve optik koherens tomografi anjiyografi (OCTA) görüntülemeleri kullanılarak makülada ve retinal vasküler yapılardaki erken dönem değişikliklerin değerlendirilmesi amaçlanmıştır. Retrospektif çalışmamız için Erzincan Binali Yıldırım Üniversitesi Göz Hastalıkları Kliniği’nde Kasım 2021 ile Kasım 2022 tarihleri arasında kliniğimizde retinal vasküler hastalık nedeniyle takip edilen, tedavilerinde anti-VEGF uyguladığımız, enjeksiyon öncesi ve sonrası erken dönemde OCT ve OCTA görüntülemeleri yapılan 30 hastanın 30 gözü dahil edilmiştir. Enjeksiyon öncesi ve sonrası (10.dakika,1.gün ve 1.hafta) OCT ve OCTA bulgularında foveal avasküler zon dışında anlamlı değişiklik saptanmıştır (p˂0,05). Retinal vaküler hastalıklara bağlı maküler ödem tedavisinde uyguladığımız anti-VEGF tedavisi sonrası akut dönemde maküla kalınlığında ve damar yoğunluğunda azalma olduğu görülmüştür. Daha geniş katılımlı çalışmalara ihtiyaç vardır.

Retinal and Choroidal Vasculature Before and After Patch Occlusion Treatment Using Optical Coherence Tomography Angiography in Patients with Amblyopia

This study aimed to investigate structural differences in the retinal and choroidal blood vessels before and after patch occlusion treatment in patients with amblyopia using optical coherence tomography angiography (OCTA) and to determine whether these differences are related to clinical improvement in patients. A total of 26 eyes of 17 patients with monocular or binocular amblyopia who underwent patch occlusion treatment for at least 1 month were retrospectively enrolled. The width of the foveal avascular zone, retinal blood vessel density, choroidal thickness, and choroidal vascularity index (CVI) measured by OCTA were compared before and after the treatment; the correlation with change in best-corrected visual acuity (BCVA) was analyzed for the data showing statistically significant differences. The mean BCVA of amblyopic eyes before and after patch occlusion treatment was 0.41 ± 0.23 and 0.25 ± 0.16 in logarithm of the minimum angle of resolution units, respectively. A decrease of about 2% in CVI was observed after the treatment (&lt;i&gt;p&lt;/i&gt; = 0.011). The correlation between the changes in CVI and the changes in BCVA were insignificant (Rs = 0.086, &lt;i&gt;p&lt;/i&gt; = 0.718). The results indicated that a decrease in CVI was observed after the patch occlusion treatment, but the relationship between CVI and BCVA could not be established. Patch occlusion treatment in amblyopia appears to affect the changes in the choroidal vessels and stroma.

Microvasculature evaluation of anisometropic amblyopia children by Angio-OCT

To compare and assess the choroidal and retinal microstructural vascularity in amblyopic eyes with the fellow eyes in anisometropic amblyopic children using angiography optical coherence tomography (Angio-OCT). Twenty-seven children (54 eyes; 5.59 ± 1.08 years old; 59.3% girls) were enrolled in this study. Choroidal thickness (CT) was measured with the use of the enhanced depth imaging mode in Angio-OCT. Parafoveal/peripapillary vascular density indices and the foveal avascular zone (FAZ) size were analyzed by MATLAB code programming on Angio-OCT images. The mean FAZ size of the amblyopic eyes were larger both in superficial and deep capillary plexus layer (SCPL/DCPL). Compared with the contralateral eyes (BCVA were normal), all the vascular density indices of SCPL and DCPL in the parafoveal and peripapillary zones were lower in the amblyopic eyes, however, the difference was insignificant (p > 0.05). No significant decrease was observed in four quadrants analyses of the amblyopic eyes (p > 0.05). Except for the measurement at 2000 µm and 1500 µm from the fovea in temple, CT in amblyopic eyes were significantly thicken than the fellow eyes (p < 0.05). Compared with the fellow eyes, the CT of certain areas were thicker in the amblyopic eyes. Though the FAZ size of the amblyopic eyes was larger in SCPL/DCPL layers, the retinal vascular density indices in SCPL/DCPL were lower in amblyopia eyes without statistical difference. Angio-OCT may be an effective way to evaluate the status of the choroidal and retinal vascular system in amblyopic children.

Distinctions between Choroidal Neovascularization and Age Macular Degeneration in Ocular Disease Predictions via Multi-Size Kernels ξcho-Weighted Median Patterns

Age-related macular degeneration is a visual disorder caused by abnormalities in a part of the eye's retina and is a leading source of blindness. The correct detection, precise location, classification, and diagnosis of choroidal neovascularization (CNV) may be challenging if the lesion is small or if Optical Coherence Tomography (OCT) images are degraded by projection and motion. This paper aims to develop an automated quantification and classification system for CNV in neovascular age-related macular degeneration using OCT angiography images. OCT angiography is a non-invasive imaging tool that visualizes retinal and choroidal physiological and pathological vascularization. The presented system is based on new retinal layers in the OCT image-specific macular diseases feature extractor, including Multi-Size Kernels ξcho-Weighted Median Patterns (MSKξMP). Computer simulations show that the proposed method: (i) outperforms current state-of-the-art methods, including deep learning techniques; and (ii) achieves an overall accuracy of 99% using ten-fold cross-validation on the Duke University dataset and over 96% on the noisy Noor Eye Hospital dataset. In addition, MSKξMP performs well in binary eye disease classifications and is more accurate than recent works in image texture descriptors.

Efficacy of a biosimilar ranibizumab monotherapy for the treatment of retinopathy of prematurity.

To evaluate the efficacy of a biosimilar ranibizumab (Razumab) on outcomes of retinopathy of prematurity (ROP) for the first time. This retrospective study included infants presenting with stage 3+ ROP either in zone 1 or zone 2 posterior or aggressive posterior ROP (APROP). All eligible infants received intravitreal razumab (0.25 mg/0.025 ml) monotherapy. Follow-up was continued monthly till complete retinal vascularization was achieved while retreatment with razumab was given when recurrent neovascularization was noted. In case of no recurrence but incomplete vascularization, laser photocoagulation was done to the residual avascular retina. We included 118 eyes of 59 infants with a median gestational age of 30 weeks and median birth weight of 1250 grams. At presentation, APROP was found in 28 eyes (24%) of 14 babies while stage 3 disease was seen in zone 1 in another 28 eyes (24%) and the remaining 62 eyes (52%) had stage 3 ROP in zone 2 posterior region. Complete resolution of ROP along with complete vascularization was seen in 22 eyes (19%) at a median of 55 days (IQR = 31-56 days) and 42 eyes (35%) showed a recurrent neovascularization at a median of 51 days post razumab (IQR = 42-55 days). The cumulative incidence of recurrence of neovascularization (21%, 95% CI = 14%-29%) peaked at seven weeks and was significantly higher in eyes with APROP (43%, 95% CI = 27%-63%) compared to eyes without APROP (13.4%, 95%CI, 8%-22%) (P < 0.001). Razumab appears to be safe and effective in treating ROP, with about a third requiring reinjection at seven weeks after the first dose.

Alterations in Retinal Vascularity in Severe Psoriasis

ABSTRACT Purpose To evaluate the changes in retinal vascularity in patients with severe psoriasis. Materials and Methods Patients with severe psoriasis [psoriasis area-severity index (PASI) >10] who did not get any systemic treatment in the last year and do not have any ocular diseases were included. All patients underwent detailed ophthalmological examination, including optical coherence tomography (OCT) and OCT angiography (OCTA). Vessel densities (VD) of Superficial (SCP) and deep (DCP) capillary plexus, foveal avascular zone (FAZ) diameter, central retinal thickness (CRT) were analyzed and compared with age-sex matched healthy adults. Results Fifty-three patients (13 F, 40 M) and 56 controls (16 F, 40 M) were included in the study. VD of SCP (50.4%±3.9 vs. 51.4%±3.2) and DCP (52.6%±6.4 vs. 55.4%±5.7) were lower in psoriasis group compared to controls (p < .05). Presence of psoriatic arthritis was related with an increased CRT (p = .000), larger FAZ and decreased foveal VD in SCP (p = .01, p = .02, respectively). Conclusion Severe psoriasis causes a decrease in retinal blood flow and presence of psoriatic arthritis is related with decreased foveal VD.

Rate of and time to complete retinal vascularization in premature infants and associated factors.

To evaluate the rate of and time to complete vascularization in premature infants and to explore associated factors. A monocentric, retrospective cohort study including 541 premature infants who underwent screening for retinopathy of prematurity (ROP) between July 2016 and June 2019. Patients underwent regular dilated fundus examinations with indirect ophthalmoscopy until complete vascularization. The worse eye of each patient was included for analyses. The proportion of infants with complete retinal vascularization at the last visit and the time to full vascularization were analyzed. Among all infants (average gestational age 31.29 ± 3.12 weeks), 490 (90.57%) had complete records of retinal vascularization outcomes, of whom 439 (89.59%) achieved complete vascularization. The average postmenstrual age (PMA) for complete vascularization was 45.39 ± 11.04 weeks, and 95.22% achieved completion before 64 weeks of PMA. ROP developed in 118 (22.56%) infants; 33 (6.10%) received anti-vascular endothelial growth factor (VEGF) treatment. For all infants screened for ROP, lower birth weight (BW), presence of ROP, and anti-VEGF therapy predicted delayed complete vascularization; for infants diagnosed with ROP, only lower BW predicted delayed complete vascularization. Subgroup analysis showed significant differences between patients without ROP, with untreated ROP, and with treated ROP in time to complete vascularization and its rate (99.7%, 66.2%, and 16.7%, respectively). Lower BW predicted delayed complete vascularization. Anti-VEGF therapy and the presence of ROP, including ROP severity, may also affect time to complete vascularization. These findings should help improve the understanding and management of persistent avascular retina in preterm infants.

Evaluation of Retinal Vascularity Index in Patients with COVID-19: A Case-Control Study.

The purpose of this study was to evaluate the impact of COVID-19 infection on retinal microvasculature by topographically mapping the retinal arteriole-to-venule ratio (AVR). In a comparative cross-sectional case-control study, fundus photos were obtained in COVID-19-infected patients and healthy controls. AVT was measured over 16 points across the retina using retinal vascularity index (RVI)-a novel semi-automated computerized parameter based on retinal vasculature. A total of 51 COVID-19-positive patients and 65 healthy controls were enrolled in the study. Overall, the mean RVI of all 16 points across the retina was 0.34 ± 0.02 in patients with COVID-19 and 0.33 ± 0.02 in control subjects (p = 0.64). Out of the 16 points being measured, three points had a statistically significant greater value in patients with COVID compared to normal controls. Localised greater RVI values were found in some of the points in COVID-19-positive patients, which likely indicates a more focal change of the vasculature.

Retinoic acid signaling in mouse retina endothelial cells is required for early angiogenic growth

The development of the retinal vasculature is essential to maintain health of the tissue, but the developmental mechanisms are not completely understood. The aim of this study was to investigate the cell-autonomous role of retinoic acid signaling in endothelial cells during retina vascular development. Using a temporal and cell-specific mouse model to disrupt retinoic acid signaling in endothelial cells in the postnatal retina (Pdgfbicre/+dnRAR403fl/fl mutants), we discovered that angiogenesis in the retina is significantly decreased with a reduction in retina vascularization, endothelial tip cell number and filipodia, and endothelial ‘crowding’ of stalk cells. Interestingly, by P15, the vasculature can overcome the early angiogenic defect and fully vascularized the retina. At P60, the vasculature is intact with no evidence of retina cell death or altered blood retinal barrier integrity. Further, we identified that the angiogenic defect seen in mutants at P6 correlates with decreased Vegfr3 expression in endothelial cells. Collectively, our work identified a previously unappreciated function for endothelial retinoic acid signaling in early retinal angiogenesis.

Evaluation of Subclinical Retinal Disease in Patients Affected by Systemic Lupus Erythematosus with No Evidence of Ocular Involvement-An Optical Coherence Tomography Angiography Original Study.

Lupus retinopathy is the second most common eye involvement in systemic lupus erythematosus (SLE), associated with significant visual deterioration and well-known negative prognostic factor for survival. Ocular manifestation in SLE, relating the retina, ranges from asymptomatic vascular involvement to vision devastating vascular occlusions. Subclinical microvascular changes are undetectable in slit lamp examination, hence are underdiagnosed. Optical coherence tomography angiography (OCTA) is a novel, easy to interpret and non-invasive technique that allows retinal vessels visualization. OCTA simplifies clinical approach and measures the severity of decreased perfusion. The aim of the study was to demonstrate the retinal vascularization in a subclinical stage of ocular involvement in a cohort of SLE patients. Thirty-three patients (57 eyes) diagnosed with SLE were enrolled into the study group and 31 healthy individuals (56 eyes) into the control group. Vessel density reduction in parafovea, inferior and nasal quadrants of superficial retinal capillary plexus in a cohort of SLE patients was found. Among study group kidney involvement was associated with further microvasculature reduction. Knowing that retinal involvement may precede other organs impairment, early detection of retinal impairment and use of OCTA as a screening modality, may decrease overall disease morbidity.

Evaluation of Circulating Platelet Extracellular Vesicles and Hypertension Mediated Organ Damage.

Elevated circulating platelet-derived extracellular vesicles (pEVs) have been associated with arterial hypertension. The role of hypertension-mediated organ damage (HMOD) to induce EV release is still unknown. We studied the micro- and macro-vascular changes (retinal vascular density and pulse wave velocity), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), and assessed the psychosocial status (anxiety and depression) in hypertensive patients to determine their relationship with EV release. Pulse wave velocity showed a significant positive correlation with pEVs (r = 0.33; p = 0.01). Systolic blood pressure (SBP) negatively correlated with retinal vascularity. The superficial retinal vascular plexus density in the whole image showed a significant negative correlation with 24 h SBP (r = −0.38, p < 0.01), day-SBP (r = −0.35, p = 0.01), and night-SBP (r = −0.27, p = 0.04). pEVs did not show significant associations with microvascular damage (retinal vascular density), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), or psychosocial status (anxiety and depression). Our results indicate that the pEV levels were associated with macrovascular damage measured by PWV, whereas no significant association between pEVs and microvascular damage, endothelial function, or emotional status could be detected. The potential utility of pEV in clinical practice in the context of HMOD may be limited to macrovascular changes.

Comparison of intravitreal injection of ranibizumab versus bevacizumab for treatment of type 1 and aggressive retinopathy of prematurity in rural Egypt. A randomized clinical trial

ObjectiveThe objective of this study is to evaluate the efficacy of intravitreal ranibizumab (IVR) monotherapy compared with intravitreal bevacizumab (IVB) monotherapy for treatment of type 1 and aggressive retinopathy of...

Subretinal Transplant of Human Amniotic Membrane in Advanced Age-Related Macular Degeneration.

Macular neovascularization (MNV) and geographic atrophy can complicate age-related macular degeneration (AMD) and lead to severe visual acuity reduction. Despite the medical treatments available, with a defect in the retinal pigmented epithelium (RPE) there is no possibility of restoring acceptable visual acuity. We evaluated postoperative outcomes in patients affected by advanced AMD who underwent subretinal implant of the human amniotic membrane (hAM) as a source of pluripotent stem cells. This retrospective, consecutive, non-randomized interventional study included 23 eyes of 21 patients affected by AMD complicated by MNV, and five eyes of five patients affected by geographic atrophy. All eyes underwent a pars plana vitrectomy, neovascular membrane removal for the MNV group, a subretinal implant of hAM, and gas tamponade, and were followed for 12 months. The primary study outcome was visual acuity improvement. Secondary outcomes were postoperative complications, OCT-angiography parameters correlated with best-corrected visual acuity (BCVA) and MNV recurrence. The mean preoperative BCVA was 1.9 logMAR, and the mean final BCVA value was 1.2 logMAR. In the MNV group, the mean BCVA improved from 1.84 logMAR to 1.26 logMAR, and from 1.84 logMAR to 1.32 logMAR in the geographic atrophy group. No MNV recurrence was evident in 12 months of follow-up. An OCT-angiography scan was used to evaluate the retinal vascularization in the treated eye, which showed a high correlation between BCVA and deep vascular density. This study demonstrates the hAM potential and safety in promoting a partial restoration of retinal function together with an increase in visual acuity.

Comparing the Clinical Viability of Automated Fundus Image Segmentation Methods

Recent methods for automatic blood vessel segmentation from fundus images have been commonly implemented as convolutional neural networks. While these networks report high values for objective metrics, the clinical viability of recovered segmentation masks remains unexplored. In this paper, we perform a pilot study to assess the clinical viability of automatically generated segmentation masks in the diagnosis of diseases affecting retinal vascularization. Five ophthalmologists with clinical experience were asked to participate in the study. The results demonstrate low classification accuracy, inferring that generated segmentation masks cannot be used as a standalone resource in general clinical practice. The results also hint at possible clinical infeasibility in experimental design. In the follow-up experiment, we evaluate the clinical quality of masks by having ophthalmologists rank generation methods. The ranking is established with high intra-observer consistency, indicating better subjective performance for a subset of tested networks. The study also demonstrates that objective metrics are not correlated with subjective metrics in retinal segmentation tasks for the methods involved, suggesting that objective metrics commonly used in scientific papers to measure the method's performance are not plausible criteria for choosing clinically robust solutions.

Quantitative vascular outgrowth and anatomic and refractive outcomes of eyes treated with bevacizumab in posterior zone Ⅰ.

To report the anatomic and refractive outcomes and retinal vascular outgrowth in eyes with posterior zone Ⅰ retinopathy of prematurity (ROP) treated with intravitreal bevacizumab (IVB). Thirty-eight eyes of 21 infants treated with IVB for type 1 and aggressive-ROP, and whose posterior border of retinal vascularization was shorter than the optic disc-to-fovea distance were defined as posterior zone Ⅰ and included in the study. Nine eyes of five infants whose follow-up time was lower than four months were accepted as insufficient for clinical outcomes. Additional treatment(s) had been performed up to 60 weeks postmenstrual age (PMA) in 10 of 29 eyes whose follow-up were higher than four months. Macula was attached at the final examination in all eyes with > 4 months follow-up. Anatomical outcome of two eyes of one infant was accepted as unfavorable whose routine follow-up was interrupted after successful initial treatment and who was presented with straightening of the temporal vascular arcade and residual fibrovascular tractional bands on the temporal periphery. The mean progression of temporal retinal vascularization was 3.6 ± 2.0 horizontal disc diameters (DD) within 7.3 weeks and 5.1 ± 2.5 horizontal DD within 69.1 weeks in the short-term (n=15) and long-term evaluated eyes (n=21), respectively. The mean spherical equivalent was -4.1 diopters at a mean age of 21 months (n=28). A favorable outcome had been achieved in almost all bevacizumab-treated eyes, but additional treatments were required. Significant progression of retinal vascularization was detected even in the eyes with short follow-up.

Defective EMC1 drives abnormal retinal angiogenesis via Wnt/β-catenin signaling and may be associated with the pathogenesis of familial exudative vitreoretinopathy

Endoplasmic reticulum (ER) membrane protein complex (EMC) is required for the co-translational insertion of newly synthesized multi-transmembrane proteins. Compromised EMC function in different cell types has been implicated in multiple diseases. Using inducible genetic mouse models, we revealed defects in retinal vascularization upon endothelial cell (EC) specific deletion of Emc1, the largest subunit of EMC. Loss of Emc1 in ECs led to reduced vascular progression and vascular density, diminished tip cell sprouts, and vascular leakage. We then performed an unbiased transcriptomic analysis on human retinal microvascular endothelial cells (HRECs) and revealed a pivotal role of EMC1 in the β-catenin signaling pathway. Further in-vitro and in-vivo experiments proved that loss of EMC1 led to compromised β-catenin signaling activity through reduced expression of Wnt receptor FZD4, which could be restored by lithium chloride (LiCl) treatment. Driven by these findings, we screened genomic DNA samples from familial exudative vitreoretinopathy (FEVR) patients and identified one heterozygous variant in EMC1 that co-segregated with FEVR phenotype in the family. In-vitro expression experiments revealed that this variant allele failed to facilitate the expression of FZD4 on the plasma membrane and activate the β-catenin signaling pathway, which might be a main cause of FEVR. In conclusion, our findings reveal that variants in EMC1 gene cause compromised β-catenin signaling activity, which may be associated with the pathogenesis of FEVR.

QUANTITATIVE ANALYSIS OF CHORIOCAPILLARIS ALTERATIONS IN SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY-ANGIOGRAPHY DURING RADIATION RETINOPATHY.

To evaluate choriocapillaris alterations following proton beam therapy irradiation using swept-source optical coherence tomography-angiography, and to assess their correlation with the grade of radiation retinopathy (RR). Eyes with uveal melanoma evaluated before and after irradiation with proton beam therapy were included, as well as the healthy fellow eye. The gradation of RR was based on a previously published classification. Choriocapillaris flow voids area was analyzed using Phansalkar thresholding. Retinal vascularization was described by foveal avascular zone (FAZ) perimeter, FAZ area, FAZ circularity index, and percentage of nonperfusion area (PAN) in the superficial capillary plexus (SCP) or deep capillary plexus. A total of 157 eyes of 83 patients were analyzed. Overall, there was a significant difference between the control group, the uveal melanoma before proton beam therapy group, and the grades of RR in the uveal melanoma after proton beam therapy group for FAZ perimeter ( P < 0.001), FAZ area ( P < 0.001), FAZ-circularity index ( P < 0.001), PAN-SCP ( P < 0.001), PAN-deep capillary plexus ( P < 0.001), and choriocapillaris flow voids area ( P < 0.001). Moreover, choriocapillaris flow voids area was significantly increased in the early stages of RR ( P = 0.003) and was further significantly correlated with FAZ perimeter ( P < 0.001), FAZ area ( P < 0.001), FAZ-circularity index ( P = 0.010), PAN-SCP ( P < 0.001), and PAN-deep capillary plexus ( P < 0.001). Quantitative optical coherence tomography-angiography alterations in the choriocapillaris microvascularization are an early biomarker of RR and are correlated to the severity of the disease.

Quantitative measures of the vascular and neural components of the retina in adult individuals with congenital and untreated growth hormone deficiency

BackgroundThe somatotrophic axis, including hypothalamic growth hormone (GH)-releasing hormone (GHRH), pituitary GH and circulating IGF-I, is critical for body size. However, the local production of GH/IGF-I (and IGF-II) and other peptides is relevant for other body functions, such as vascular, brain, and retinal function. The consequences of GH deficiency (GHD) on the retinal structure are still unclear, possibly reflecting the heterogeneity of patients and the different types of assessment in previous publications. Our purpose was to assess quantitative measures of the vascular and neural components of the retina in subjects with severe congenital isolated GHD (IGHD).MethodsA cross-sectional study was carried out in 25 adult IGHD subjects and 25 age- and gender-matched controls. Interview, physical examination, laboratory data, optical coherence tomography (OCT) and OCT angiography (OCTA) were performed.ResultsOCT revealed no difference in the areas of the nerve fiber layer average, nor in the areas of superior, inferior, or nasal quadrants, between the two groups. However, areas of the temporal quadrant (p = 0.041), the optical disc (p = 0.042), the cup (p < 0.0001), as well as the cup/disc ratio (p < 0.0001), were higher in IGHD subjects than controls. The rim area was smaller (p = 0.002), although still normal. In OCTA, there was no difference in the minimum foveal thickness, central fovea, foveal avascular zone, and retinal density in any assessed area.ConclusionsIn conclusion, congenital IGHD does not affect quantitative measures of the vascular and neural retina, and it is associated with increased optical disc in this genetically homogeneous cohort.

Relationship between refractive outcomes and quantitative retinal vascularization and severity of plus disease in eyes treated with intravitreal bevacizumab.

The study aimed to investigate the relationship between refractive outcomes with the extent of retinal vascularization and severity of the plus disease in infants treated with intravitreal bevacizumab (IVB). Pre-IVB fundus images (PFIs), final fundus images (FFIs), and refractive outcomes of the 93 infants who underwent IVB monotherapy for type 1 and aggressive retinopathy of prematurity (A-ROP) were retrospectively evaluated. Quantitative measurements were performed on PFIs and FFIs. Pre-IVB plus severity was scored on a five-leveled scale. Correlation between spherical equivalent (SE) with pre-treatment and final extent of the temporal retinal vascularization and pre-treatment severity of plus disease was analyzed. There was a linear and low positive correlation between the extent of pre-IVB and final temporal retinal vascularization with final SE (p = 0.000, r = 0.267; P = 0.002, r = 0.274, respectively). There was a low negative correlation between the pre-IVB plus severity score with final SE (p = 0.012, r = -0.192). Gestational age (GA), birth weight (BW), IVB dose, presence of additional IVB, or laser treatments were not correlated with refractive outcome. Out of 171 eyes, 38 eyes had >1 D myopia. In the univariate logistic analyses, pre-IVB retinal zone and pre-IVB and final extent of the temporal retinal vascularization were found to be related to the development of >1 D myopia (p = 0.002, odds ratio (OR) = 0.298; P = 0.000, OR = 0.281; P = 0.001, OR = 0.317; respectively). Our study indicates that the pre-treatment and final extent of retinal vascularization were the main parameters that were related to final refractive outcomes in IVB-treated eyes for type 1 and A-ROP.