Twelve-year follow up of a case of autosomal recessive bestrophinopathy with transient resolution of retinal edema in one eye

Purpose To report 12-year follow-up of a patient with ARB. Case report A 25-year-old man presented with blurred vision in his both eyes (OU). Best-corrected visual acuity (BCVA) was 20/63 Snellen equivalent in the right eye (OD) and 20/32 Snellen equivalent in the left eye. The intraocular pressures and anterior segment examination were unrevealing in OU. Posterior segment examination revealed multiple yellowish flecks and dots in the posterior pole in OU. Optical coherence tomography (OCT) showed subretinal fluid (SRF), intraretinal hyporeflective spaces, elongated and shaggy photoreceptors and outer retinal defects. Fundus autofluorescence demonstrated mottling hyperautofluorescence and hypoautofluorescence in the posterior pole in OU. Fluorescein angiography illustrated hyperfluorescence in the posterior pole and surrounding the arcades in OU. Multifocal electroretinography objectified mild to markedly abnormal responses in all ring areas in OU. Molecular genetic testing confirmed two heterozygous sequence variations in the BEST1 gene. At 4 years of follow-up, OCT revealed a complete resolution of SRF and a partial resolution of intraretinal hyporeflective spaces in the OD with corresponding improvement in the BCVA to 20/23 Snellen equivalent in the OD, even though outer retinal defects persisted. Our patient denied recent changes in his alimentary habits and medical history at that time. Posteriorly, SRF and intraretinal hyporeflective spaces reappeared in the OD. Conclusion To the best of our knowledge, this is the first case report of ARB with a transient resolution of retinal edema in one eye without medical treatment and dietary therapy.

Fundus Examination in Pediatric Patients

There are a number of different pieces of equipment and techniques available for examination of the fundus of a pediatric patient. Two of these tools are handheld devices, the direct ophthalmoscope and PanOpticTM ophthalmoscope. Both of these devices allow for examination of the posterior pole of the eye. This chapter will discuss the indications, advantages, and disadvantages of both of these pieces of equipment in addition to how to use the equipment to examine the posterior segment of a pediatric patient.

Choroidal caverns in pachychoroid neovasculopathy

Background. Choroid plays an important role in the pathogenesis of retinal pathology. Choroidal cavern, a recently identifi ed fi nding of optical coherent tomography (OCT), has been described in some degenerative and atrophic forms of retinal pathology. In the literature, there are only a few studies of choroidal cavers in pachychoroid neovasculopathy, newly described form of age related macular degeneration.The aim: to perform a detailed analysis of choroidal structure on OCT scans of patients with pachychoroid neovasculopathy and to reveal the frequency of choroidal caverns identifi cation.Material and methods. The data of 30 patients (30 eyes) aged 64.4 ± 5.6 years with pachychoroid neovascularization were retrospectively analyzed. The patients underwent spectral OCT and OCT-angiography (OCTA) using a Spectralis device (Heidelberg Engineering, Germany). The protocol was “Posterior Pole”, consisting of 61 scans. To assess the structure of the choroid, an enhanced image depth (EDI) module was used. OCT angiography was performed with a scan area of 6 × 6 mm. These methods were compared to identify choroidal caverns.Results. On OCT subretinal type 1 neovascularization was revealed as a fl at detachment of the pigment epithelium and visualization of blood flow on OCTA in the lesion as angled vessels (21 eyes) or a seafan (9 eyes). On OCT-EDI scans, there was diffuse or local choroidal thickening of choroid with an increase in the vessels of the Haller’s layer and thinning of the choriocapillaries. Choroidal caverns appeared on OCT and en-face OCT as areas with low optical density, round or irregular, located in different layers of the chorioid, without hyperrefl ective boundaries. A typical sign of choroidal cavern is the tail of hypertransmission after the cavern toward the sclera. Choroidal caverns were found in 4 of 30 eyes (13.3 %) and were located both near the choroidal neovascularization lesion and beyond this area.Conclusion. The prevalence of choroidal cavities, a new choroidal biomarker, in pachychoroid neovasculopathy was 13.3 %. Identification of these changes is possible with the use of modern diagnostic techniques (OCT-EDI, OCTA and en-face OCT) that allow visualization the state of the choroid. The prognostic signifi cance of choroidal cavities requires further study.

Treatment outcomes of central retinopathy of prematurity with localization in the Moscow regional perinatal center

BACKGROUND: Ranibizumab is widely used in retinopathy of prematurity. Therefore, it is necessary to evaluate the effectiveness, the risk of complications, and recurrence of the disease by antiangiogenic therapy. AIM: To demonstrate the experience of using anti-VEGF drugs in the Moscow Regional Perinatal Center and the effectiveness of different approaches to retinopathy of prematurity (ROP) treatment in the central retinal zone. MATERIAL AND METHODS: The case histories of 17 deeply premature infants with threshold ROP stages and localization in the posterior pole were retrospectively analyzed. Children were treated with intravitreal VEGF inhibitor (total 9 children), 5 children underwent laser coagulation of the retina, and 3 children received combined treatment (laser and intravitreal administration of a VEGF inhibitor). RESULTS: The average age of development of threshold stages was 35.2 weeks (range: 30.539 weeks) in our study. The frequency of promising outcomes after using anti-VEGF drugs alone or in conjunction with peripheral laser treatment was 100%. In comparison, the only laser treatment generated a promising result in 70% of the eyes. However, ROP relapses after anti-VEGF therapy developed at 37, 43, 44,5 weeks. In addition, 1 out of 9 children developed a recurrence of ROP and required laser treatment 7 weeks after using anti-VEGF. CONCLUSION: The use of anti-VEGF therapy is an effective method for the treatment of ROP of the posterior pole. However, there is the ambiguity of the available recommendations on the further management of children. Therefore, it is necessary to monitor the children who have received antiangiogenic therapy for as long as possible.

Extensive loss of Wnt genes in Tardigrada

Background Wnt genes code for ligands that activate signaling pathways during development in Metazoa. Through the canonical Wnt (cWnt) signaling pathway, these genes regulate important processes in bilaterian development, such as establishing the anteroposterior axis and posterior growth. In Arthropoda, Wnt ligands also regulate segment polarity, and outgrowth and patterning of developing appendages. Arthropods are part of a lineage called Panarthropoda that includes Onychophora and Tardigrada. Previous studies revealed potential roles of Wnt genes in regulating posterior growth, segment polarity, and growth and patterning of legs in Onychophora. Unlike most other panarthropods, tardigrades lack posterior growth, but retain segmentation and appendages. Here, we investigated Wnt genes in tardigrades to gain insight into potential roles that these genes play during development of the highly compact and miniaturized tardigrade body plan. Results We analyzed published genomes for two representatives of Tardigrada, Hypsibius exemplaris and Ramazzottius varieornatus. We identified single orthologs of Wnt4, Wnt5, Wnt9, Wnt11, and WntA, as well as two Wnt16 paralogs in both tardigrade genomes. We only found a Wnt2 ortholog in H. exemplaris. We could not identify orthologs of Wnt1, Wnt6, Wnt7, Wnt8, or Wnt10. We identified most other components of cWnt signaling in both tardigrade genomes. However, we were unable to identify an ortholog of arrow/Lrp5/6, a gene that codes for a Frizzled co-receptor of Wnt ligands. Additionally, we found that some other animals that have lost several Wnt genes and are secondarily miniaturized, like tardigrades, are also missing an ortholog of arrow/Lrp5/6. We analyzed the embryonic expression patterns of Wnt genes in H. exemplaris during developmental stages that span the establishment of the AP axis through segmentation and leg development. We detected expression of all Wnt genes in H. exemplaris besides one of the Wnt16 paralogs. During embryo elongation, expression of several Wnt genes was restricted to the posterior pole or a region between the anterior and posterior poles. Wnt genes were expressed in distinct patterns during segmentation and development of legs in H. exemplaris, rather than in broadly overlapping patterns. Conclusions Our results indicate that Wnt signaling has been highly modified in Tardigrada. While most components of cWnt signaling are conserved in tardigrades, we conclude that tardigrades have lost Wnt1, Wnt6, Wnt7, Wnt8, and Wnt10, along with arrow/Lrp5/6. Our expression data may indicate a conserved role of Wnt genes in specifying posterior identities during establishment of the AP axis. However, the loss of several Wnt genes and the distinct expression patterns of Wnt genes during segmentation and leg development may indicate that combinatorial interactions among Wnt genes are less important during tardigrade development compared to many other animals. Based on our results, and comparisons to previous studies, we speculate that the loss of several Wnt genes in Tardigrada may be related to a reduced number of cells and simplified development that accompanied miniaturization and anatomical simplification in this lineage.

Decreasing myopic lacquer crack and widening parapapillary gamma zone: case report

Background Myopic axial elongation may be due to an equatorial enlargement of Bruch’s membrane (BM), leading to a prolate eye shape and increasing strain with BM and the retinal pigment epithelium (RPE) layer at the posterior pole. The increased BM strain may cause an enlargement of Bruch’s membrane opening (BMO) of the optic nerve head, with the subsequent development and enlargement of parapapillary gamma zone as BM-free parapapillary zone. The increased strain within BM and RPE may also cause lacquer cracks (LCs) as linear breaks in the RPE and / or BM. Studies suggested that a more marked gamma zone enlargement is associated with lower prevalence of LCs or macular BM defects. Here report on the disappearance of a LC during a 10-year follow-up of a highly myopic eye, concurrent with a marked increase in gamma zone. Case presentation A 56-year-old woman showed in her right eye (axial length measured 30.69 mm) a LC, vertically oval optic disc, and parapapillary gamma zone in 2001. When re-examined in 2006, gamma zone had enlarged, while the LC was no longer detectable. In 2011, the LC was not visible neither upon ophthalmoscopy and or upon optical coherence tomography (OCT), while gamma zone had further enlarged. The gamma zone enlargement occurred in a direction perpendicular to the direction of the former LC. Conclusions The observation suggest that a LC can decrease in width, in temporal association with an enlargement of gamma zone. It fits with the notion that an enlargement of the BMO (i.e., enlarging gamma zone) may lead to a relaxation of the BM strain and subsequently to a decrease in the width of the LC.

Wide-field swept source optical coherence tomography evaluation of posterior segment changes in highly myopic eyes

Background To investigate the features in the posterior pole of highly myopic (HM) eyes using a wide-field high-resolution swept source optical coherence tomography (SS OCT). Methods This observational cross-sectional study involved 262 eyes of 139 patients, who were diagnosed as HM and had consecutively been examined by SS OCT in the Ophthalmology Department of the Peking Union Medical College Hospital between March 2019 and December 2019. The characteristics of OCT images were documented and analyzed. Results In our study, SS OCT could demonstrate the entire layer of the choroid and detect the sclera in all eyes. The mean subfoveal retinal/choroidal/scleral thickness were 204.84 ± 119.86 μm, 92.80 ± 75.78 μm and 394.734 ± 123.09 μm, respectively. 138 eyes (52.67%) had posterior precortical vitreous pocket. Myopic foveoschisis was detected in 110 eyes (41.98%), and significantly associated with the presence of posterior staphyloma. 36 eyes (13.74%) had DSM in our study, of which 8 eyes (22.22%) showed a round dome, 16 (44.44%) were horizontal oval-shaped, 9 (25%) were vertical oval-shaped and 3 (8.34%) were oblique oval-shaped. Both SFCT and SFST were inversely and significantly associated with age and refractive errors. Macular neovascularization was significantly correlated with intrascleral vessels. Different deformation of the sclera and posterior staphyloma were vividly identified on SS OCT images. Conclusions This study provided a relatively comprehensive picture of posterior pole in HM eyes. Such good visualization of ocular fundus provided by wide-field SS OCT could be useful for the therapy option, disease condition monitoring and pathogenesis investigation.

Validation of computer-aided diagnosis of diabetic retinopathy from retinal photographs of diabetic patients from Telecamps

Objective: To validate an algorithm previously developed by the Healthcare Technology Innovation Centre, IIT Madras, India for screening of diabetic retinopathy (DR), in fundus images of diabetic patients from telecamps to examine the screening performance for DR. Design: Photographs of patients with diabetes were examined using the automated algorithm for the detection of DR Setting: Mobile Teleophthalmology camps were conducted in two districts in Tamil Nadu, India from Jan 2015 to May 2017. Participants: 939 eyes of 472 diabetic patients were examined at Mobile Teleophthalmology camps in Thiruvallur and Kanchipuram districts, Tamil Nadu, India,. Fundus images were obtained (40-45-degree posterior pole in each eye) for all patients using a nonmydriatic fundus camera by the fundus photographer. Main Outcome Measures: Fundus images were evaluated for presence or absence of DR using a computer-assisted algorithm, by an ophthalmologist at a tertiary eye care centre (reference standard) and by a fundus photographer. Results: The algorithm demonstrated 85% sensitivity and 80% specificity in detecting DR compared to ophthalmologist. The area under the receiver operating characteristic curve was 0.69 (95%CI=0.65 to 0.73). The algorithm identified 100% of vision-threatening retinopathy just like the ophthalmologist. When compared to the photographer, the algorithm demonstrated 81% sensitivity and 78% specificity. The sensitivity of the photographer to detect DR was found to be 86% and specificity was 99% in detecting DR compared to ophthalmologist. Conclusions: The algorithm can detect the presence or absence of DR in diabetic patients. All findings of vision-threatening retinopathy could be detected with reasonable accuracy and will help to reduce the workload for human graders in remote areas.

Subclinical Signs of Retinal Involvement in Hereditary Angioedema

To explore retinal abnormalities using spectral domain optical coherence tomography (SD-OCT) and OCT-angiography (OCT-A) in a highly selective cohort of patients with type I hereditary angioedema (HAE). This prospective case-control study included 40 type I HAE patients and 40 age-/sex-matched healthy subjects (HC). All participants underwent SD-OCT-scanning of retinal posterior pole (PP), peripapillary retinal nerve fiber layer (pRNFL), and optic nerve head (ONH). Superficial/deep capillary density was analyzed by OCT-A. A total of 80 eyes from 40 HAE and 40 eyes from HC were evaluated. The pRNFL was thicker in HAE than in HC in nasal superior (p < 0.0001) and temporal quadrants (p = 0.0005 left, p = 0.003 right). The ONH thickness in HAE patients was greater than in HC in the nasal (p = 0.008 left, p = 0.01 right), temporal (p = 0.0005 left, p = 0.003 right), temporal inferior (p = 0.007 left, p = 0.0008 right), and global (p = 0.005 left, p = 0.007 right) scans. Compared to HC, HAE showed a lower capillary density in both superficial (p = 0.001 left, p = 0.006 right) and deep (p = 0.008 left, p = 0.004 right) whole images, and superficial (p = 0.03 left) and deep parafoveal (p = 0.007 left, p = 0.005 right) areas. Our findings documented subclinical retinal abnormalities in type I HAE, supporting a potential role of the retinal assessment by SD-OCT/OCT-A as a useful tool in the comprehensive care of HAE patients.

Histology of neovascular myopic macular degeneration

To assess the histological correlate of neovascular or exudative myopic macular degeneration (nMMD) in highly myopic human eyes, we examined histomorphometrically histologic sections of enucleated eyes of Caucasian patients. The study included 284 eyes (age: 61.9 ± 13.7 years; range: 24–89 years; axial length: 25.5 ± 3.1 mm; range: 20–37 mm). An nMMD was detected in 5 eyes (axial length: 29.6 ± 2.6 mm; range: 26.0–31.0 mm). All these eyes showed within or close to the nMMD a macular Bruch’s membrane (BM) defect, fibrous tissue with erythrocyte-filled blood vessels, and proliferations of irregularly pigmented and irregularly piled-up retinal pigment epithelium (RPE) cells each of which was connected with a curled-up, PAS (Periodic-Acid-Shiff)-positive membrane. The nMMD lesions were covered by proliferated RPE cells. RPE cells were not detected within the retina. In binary regression analysis, a higher nMMD prevalence was associated with a higher prevalence of macular BM defects (odds ratio: > 1000; P < 0.001), while the association with axial length was not significant (P = 0.43) in that model. After adjustment for the presence of macular BM defects, the nMMD prevalence was not associated with BM thickness (measured at the posterior pole, equator-posterior pole midpoint, equator and shortly posterior to the ora serrata) (P = 0.10; P = 0.87; P = 0.40; and P = 0.36, respectively), RPE cell layer thickness (P = 0.83; P = 0.79; P = 0.31; P = 0.38, resp.), RPE cell density (P = 0.56; P = 0.91; P = 0.47; P = 0.87, resp.), choriocapillaris thickness (P = 0.47; P = 0.93; P = 0.41; P = 0.75, resp.), and choriocapillaris density (P = 0.99; P = 0.94; P = 0.17; P = 0.97, resp.). The results suggest that nMMD is characterized by a fibrous pseudo-metaplasia of the RPE and is strongly associated with macular BM defects, without other detected histomorphometric differences in thickness or density of the RPE, BM, and choriocapillaris.