A Straightforward Bifurcation Pattern-Based Fundus Image Registration Method.

Fundus image registration is crucial in eye disease examination, as it enables the alignment of overlapping fundus images, facilitating a comprehensive assessment of conditions like diabetic retinopathy, where a single image's limited field of view might be insufficient. By combining multiple images, the field of view for retinal analysis is extended, and resolution is enhanced through super-resolution imaging. Moreover, this method facilitates patient follow-up through longitudinal studies. This paper proposes a straightforward method for fundus image registration based on bifurcations, which serve as prominent landmarks. The approach aims to establish a baseline for fundus image registration using these landmarks as feature points, addressing the current challenge of validation in this field. The proposed approach involves the use of a robust vascular tree segmentation method to detect feature points within a specified range. The method involves coarse vessel segmentation to analyze patterns in the skeleton of the segmentation foreground, followed by feature description based on the generation of a histogram of oriented gradients and determination of image relation through a transformation matrix. Image blending produces a seamless registered image. Evaluation on the FIRE dataset using registration error as the key parameter for accuracy demonstrates the method's effectiveness. The results show the superior performance of the proposed method compared to other techniques using vessel-based feature extraction or partially based on SURF, achieving an area under the curve of 0.526 for the entire FIRE dataset.

Study on the effects of different anti-VEGF drugs on fibrovascular membranes of proliferative diabetic retinopathy.

PURPOSE: To investigate the effects of different anti-VEGF drugs on fibrovascular membranes (FVM) in proliferative diabetic retinopathy (PDR). In addition, in vitro model was used to simulate the intraocular fibroblasts barrier to explore the penetration of different anti-VEGF drugs. METHODS: 24 eyes from 24 PDR patients with FVM were recruited for this prospective observational study. The patients were randomized to receive one of three anti-VEGF drugs (Ranibizumab, Conbercept, or Aflibercept). Then neovascular structures were assessed by optical coherence tomography angiography (OCTA) before intravitreal injection (pre-IVT) and 1, 2, and 3 days after intravitreal injection (post-IVT). The changes in vessels area (VSA), vessels percentage area (VPA), junction density (JD), and average lacunarity (AL) were analyzed by using the image processing software Angiotool. In vitro penetrating model with fibroblasts barrier was used to compare the effects of the three drugs on human retinal vascular endothelial cells (HRVECs) over 3 days by Cell proliferation measurement. Moreover, the drug concentrations in the penetrating model were detected by liquid chromatography-mass spectrometry (LC-MS). RESULTS: The VSA, VPA, and JD all decreased, while the AL increased in Ranibizumab group(n = 8), Conbercept group (n = 8), and Aflibercept group (n = 8) within 3 days (P<0.05). Meanwhile, under the condition of the same amount of substance, the inhibition effect of Ranibizumab on HRVEC was the strongest in the penetrating model evaluated by CCK8 absorbance experiments of HRVECs (FCCK8=6.493, PCCK8= 0.0051), and the number of transmembrane molecules in the Ranibizumab group was also the largest within 3 days (F = 8.209, P = 0.0006) among the three groups. CONCLUSION: Angiotool is feasible to reconstruct the neovascular structure on the FVM in OCTA images. The three different anti-VEGF drugs can significantly reduce the vascular area and density on the proliferating membranes, and there is no significant difference in the anti-neovascularization among the three drugs clinically. However, small molecule drug is more penetrating and move faster across membranes in vitro cell model. CLINICAL TRIAL REGISTRATION: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2300067476).

FEATURES OF VASCULATURE IN PATIENTS WITH RETINA ARTERIAL MACROANEURYSM USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess morphologic characteristics of retinal arterial macroaneurysm (RAM) and their vascular changes using optical coherence tomography angiography (OCTA). METHODS: This observational study included 31 eyes of 29 participants diagnosed with RAM based on fundus fluorescein angiography in Tianjin Medical University Eye Hospital. Multimodal imaging modalities, including fundus photography, fluorescein angiography, and OCTA, were used to examine RAMs. The demographic and clinical characteristics of the RAMs were recorded. RESULTS: Depending on the fundus fluorescein angiography examination, 40 cases of RAM were confirmed in 29 patients. Twenty-three patients were female (79%), and six patients were male (21%). Two patients had binocular RAM, and four eyes had more than one RAMs. Relying on the OCTA technology, RAMs have four different vascular morphology types (i.e., distended, meshed, malformed, and occult types). In the distended type, round or encircled thrombi caused asymmetrical or symmetrical distention of retinal arteriolar, leading to separate true lumen and false thrombus lumen in RAM. In the meshed type, the meshed or dendritic vascular network around the RAM was likely to be the neovascularization due to the ischemia and hypoxia of the arteriolar wall. Finally, in the malformed and occult type, the RAM usually regressed, and the retinal arterioles were remodeled to distorted or normal arterioles accompanied by capillary degradation. CONCLUSION: Relying on the OCTA technology, we found that the RAMs have four different types of vascular morphology. Each group of RAM has different vascular features. The application of OCTA in patients with RAM furthers our understanding of the vasculature of RAMs.

WF SS-OCTA for detecting diabetic retinopathy and evaluating the effect of photocoagulation on posterior vitreous detachment.

Purpose: This study aimed to assess the clinical usefulness of widefield swept source optical coherence tomography angiography (WF SS-OCTA) for detecting microvasculature lesions in diabetic retinopathy (DR) by comparing it with ultra-widefield fluorescein angiography (UWFFA) and to investigate the effect of panretinal photocoagulation (PRP) on posterior vitreous detachment (PVD) status. Methods: Patients with severe non-proliferative DR (NPDR) or proliferative DR (PDR) who were initially treated with PRP were enrolled. They underwent WF SS-OCTA with a 12×12-mm scan pattern of five visual fixations at baseline and at least a 3-month follow-up after PRP treatment. Patients with no contraindications underwent imaging with UWFFA within a week. Images were evaluated using two methods for the areas of the visible field of view (FOV), non-perfusion area (NPA), presence of neovascularization of the disc (NVD), neovascularization elsewhere (NVE), and PVD status. Results: In total, 44 eyes of 28 patients with DR that were initially treated with PRP were analyzed. The FOV of the UWFFA was significantly wider than that of the WF SS-OCTA. The quantitative measurement of the NPAs was consistent between the two methods. NPAs more than 5DA outside the panoramic OCTA imaging area were detected in 1 eye with NPDR (8.3%) and in 10 eyes with PDR (47.8%). WF SS-OCTA had high detection rates for NVDs and NVEs, with a low rate of false positives. After PRP treatment, no eyes indicated progression in the PVD stages around the macula, optical disc, or NVEs at the short follow-up. Conclusion: WF SS-OCTA is clinically useful for evaluating NPAs and neovascularization in DR. PRP treatment does not induce PVD development in the short term.

Multiple Preprocessing Hybrid Level Set Model for Optic Disc Segmentation in Fundus Images.

The accurate segmentation of the optic disc (OD) in fundus images is a crucial step for the analysis of many retinal diseases. However, because of problems such as vascular occlusion, parapapillary atrophy (PPA), and low contrast, accurate OD segmentation is still a challenging task. Therefore, this paper proposes a multiple preprocessing hybrid level set model (HLSM) based on area and shape for OD segmentation. The area-based term represents the difference of average pixel values between the inside and outside of a contour, while the shape-based term measures the distance between a prior shape model and the contour. The average intersection over union (IoU) of the proposed method was 0.9275, and the average four-side evaluation (FSE) was 4.6426 on a public dataset with narrow-angle fundus images. The IoU was 0.8179 and the average FSE was 3.5946 on a wide-angle fundus image dataset compiled from a hospital. The results indicate that the proposed multiple preprocessing HLSM is effective in OD segmentation.

Novel mutations of the USH2A gene cause Usher syndrome in five Chinese families.

BACKGROUND: Usher syndrome (USH) is a leading disorder of deaf-blindness. The phenotypic and genetic heterogeneity of USH makes the diagnosis of this disorder difficult. However, diagnosis can be facilitated by employing molecular approaches, especially for diseases without pronounced pathognomonic symptoms. Therefore, this study aimed to reveal the genetic defects in five USH patients using clinical targeted exome sequencing (TES). METHODS: USH patients and their family members from five unrelated Chinese USH families were recruited and subjected to TES. Ophthalmic information was obtained for all patients to ensure a meaningful interpretation. The TES data were analysed using an established bioinformatics pipeline to identify causative mutations. Further verification by Sanger sequencing and cosegregation analysis were performed on available family members. RESULTS: We identified genetic mutations in five USH patients using TES. Seven mutations, four of which were novel, were identified in the USH2A gene. One proband (F1-II-3) was found to have a homozygous mutation inherited from nonconsanguineous parents, and another proband (F5-III-1) was found to carry three USH2A gene mutations. CONCLUSION: In conclusion, the study revealed the importance of TES in the clinical diagnosis of USH patients with variable phenotypes. The correlation between USH2A gene mutations and clinical phenotypes will help to refine the clinical diagnosis of USH.

Targeted exome sequencing identified a novel USH2A mutation in a Chinese usher syndrome family: a case report.

BACKGROUND: Usher syndrome is a disease with a heterogeneous phenotype and genotype. Our purpose was to identify the gene mutation in a Chinese family with Usher syndrome type 2 and describe the clinical features. CASE PRESENTATION: A 23-year-old man complained of a 10-year duration of nyctalopia and a 3-year decline in visual acuity of both eyes accompanied by congenital dysaudia. To clarify the diagnosis, the clinical symptoms were observed and analysed in combination with comprehensive ophthalmologic examinations as well as genetic analysis (targeted exome sequencing, TES). A typical clinical presentation of Usher syndrome of the fundus was found, including a waxy yellow-like disc, bone-spicule formations and retinal vessel stenosis. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) showed loss of the ellipsoid zone and a reduction in paracaval vessel density in both eyes. Genetic analysis identified a novel homozygous c.8483_8486del (p.Ser2828*) mutation in USH2A. The mutation resulted in premature termination of translation and caused the deletion of 19 fibronectin type 3 domains (FN3), transmembrane (TM) region and PDZ-binding motif domain, which play an important role in protein binding. After combining the clinical manifestations and genetic results, the patient was diagnosed with Usher syndrome type 2. CONCLUSION: We found a novel c.8483_8486del mutation in the USH2A gene through TES techniques. The results broaden the spectrum of mutations in Usher syndrome type 2 and suggest that a combination of clinical information and molecular diagnosis via TES could help Usher syndrome patients obtain a better diagnosis.

Novel mutations in the OPN1LW and NR2R3 genes in a patient with blue cone monochromacy.

BACKGROUND: To clarify the diagnosis of a Chinese patient with novel double heterozygous in the NR2E3 and OPN1LW genes and describe the clinical features. MATERIALS AND METHODS: A 47-year-old man presented with an 8-year history of decreased vision and poor night vision. Based on his clinical phenotype, we focused on 36 genes associated with these characteristics. Possible pathogenic mutation sites were screened by next-generation sequencing (NGS), which showed novel mutations in the NR2E3 and OPN1LW genes. These mutations were confirmed in the patient's sister and daughter by Sanger sequencing. To clarify the diagnosis, the clinical symptoms of the patient were observed and analyzed in combination with comprehensive ophthalmologic examinations. RESULTS: Genetic analysis identified the presence of novel double heterozygous of c.361G>A; p.E121K in NR2E3, a gene responsible for enhanced S-cone syndrome (ESCS; OMIM #268100) and c.244A>G; p.K82E in OPN1LW, a gene responsible for blue cone monochromacy (BCM; OMIM#303700). No typical clinical presentation or fundus features were found. The differential diagnosis of ESCS was excluded by electroretinography (ERG) due to the lack of characteristic abnormalities associated with ESCS. Based on the clinical manifestations and comprehensive ophthalmologic examinations, the patient was diagnosed with BCM. CONCLUSIONS: The novel mutations of c.244A>G; p.K82E in the OPN1LW gene and c.361G>A; p.E121K in the NR2E3 gene both cause BCM, but OPN1LW gene mutation dominated the retinal degeneration, resulting in the clinical features observed in this patient. These novel double heterozygous may be helpful for future genetic diagnosis and treatment for BCM.

Comparison of the efficacy of intravitreal ranibizumab for choroidal neovascularization due to pathological myopia with and without a dome-shaped macula.

Ranibizumab injection in the treatment of choroidal neovascularization (CNV) secondary to pathologic myopia (PM) with and without a dome-shaped macula (DSM).Prospective observational study.A total of 24 patients (24 eyes) with angiographic evidence of CNV secondary to PM were divided into 2 groups: eyes with a DSM and eyes without DSM. All patients received a baseline intravitreal ranibizumab injection. Additional injections were considered at each follow-up visit. Best-corrected visual acuity (BCVA) and optical coherence tomography were tested monthly through 12 months of follow-up. The mean changes in BCVA, central retinal thickness (CRT, including retinal and CNV thickness), and the number of injections were evaluated.There were no significant differences in visual outcomes between the groups over 12 months (P > .05). Patients with a DSM had a mean change in BCVA of +8.7 letters compared with +14.2 letters in patients without a DSM (P = .68). However, there were more patients without a DSM who gained at least 15 letters from baseline compared with patients with a DSM. By the end of the follow-up, there was no significant difference in the mean change in baseline CRT between patients with and without a DSM (-65.0 and -90.7, respectively, P = .42). The mean number of injections was 8.83 in the patients with DSM and 8.17 in the patients without a DSM (P > .05).For the pathological myopia patients who had CNV with a DSM, the DSM did not alter the effect of the ranibizumab treatment. There was no difference in the visual improvement, anatomic benefit and number of treatments between the 2 groups.

Diode laser transscleral cyclophotocoagulation followed by phacotrabeculectomy on medically unresponsive acute primary angle closure eyes: the long-term result.

BACKGROUND: To explore the intraocular pressure-lowering effect and complications of diode laser transscleral cyclophotocoagulation (DLTSC) followed by phacotrabeculectomy on medically unresponsive acute primary angle closure eyes. METHODS: Nine eyes of nine medically unresponsive acute primary angle closure patients were enrolled. All the patients underwent cyclophotocoagulation followed by phacotrabeculectomy to control the prolonged acute attack. Data were recorded prospectively and then analyzed retrospectively. The reduction in intraocular pressure, improvement of vision and the complications were evaluated. RESULTS: After DLTSC, the IOP of all the patients were reduced, but all were above 21 mmHg under topical anti-glaucoma medications. After phacotrabeculectomy, the IOP of all the patients was decreased. At the final visit, the vision of all the patients was improved and the IOP of all the patients was below 21 mmHg without anti-glaucoma medications. There were no complications during the DLTSC and phacotrabeculectomy. Uveitis was the common complications after the both procedures, which were resolved by medication treatment. CONCLUSION: Diode laser transscleral cyclophotocoagulation followed by phacotrabeculectomy is an alternative procedure to control the intraocular pressure of medically unresponsive acute primary angle closure eyes with few complications.

[Transplantation of porcine type I atelocollagen into rabbit cornea].

OBJECTIVE: To investigate corneal wound healing in rabbit after lamellar keratoplasty with porcine type I atelocollagen. METHODS: One hundred Chinese white rabbits, 80 rabbits were randomly divided into collagen materials group (group A) and allograft group (group B), and group A and B were operated for the lamellar keratoplasty in one eye. Rest 20 rabbits' eyes (40 eyes) were used as the source of allograft for group B. After operation, the rabbits' eyes were observed by naked eyes and slit lamp, and recorded the score of the transparency and neovascularization of the cornea. The rabbits were sacrificed at 3rd, 14th day, the 1st, 3rd, and 6th month (each group eight eyes). The corneas were observed by histopathology, and the epithelial cells marker protein K3 were detected by immunohistochemistry. The results were analyzed by Rank sum test. RESULTS: The transparency of the cornea was increased gradually in A and B groups, and reached the peak on the 6th month (group A: χ(2) = 31.250, P = 0.000; group B: χ(2) = 32.566, P = 0.000). The difference had not statistics significance in the comparison of the transparency from the 1st to 6th month (Z = -1.414, 0.000, -0.743;P = 0.157, 1.000, 0.458). The two groups had corneal neovascularization after 7 days, the intensity of corneal neovascularization in A group increased gradually, reached the peak on day 14, then decreased gradually (χ(2) = 20.727, P = 0.001); the intensity of corneal neovascularization in B group increased gradually, reached the peak on day 14, and then decreased gradually (χ(2) = 25.562, P = 0.000). The difference had statistics significance in the comparison of the neovascularization of the cornea on the 6th month between A and B group (Z = -2.070, P = 0.038). Histopathology showed the collagen material nearly disappeared after 1 month of surgery and arrangement of collagen tends to be regular. On the 6th month, arrayed collagen was regular in general, but disordered partly. CONCLUSIONS: Porcine type I atelocollagen can promote corneal cells regeneration. But it needs more study to be a cornea substitute that can completely replace the corneal allograft.