Macular Pathology Research Articles

Progressive maculopathy in a child resulting from vitreopapillary traction on a congenitally anomalous nerve.

To present a case of worsening maculopathy and vision loss due to vitreopapillary traction associated with an anomalous optic nerve head in a pediatric patient successfully managed with pars plana vitrectomy. Retrospective case report. A 13-year-old boy presented with unilateral maculopathy that slowly progressed over a four-year period. As his visual acuity declined, he became increasingly symptomatic. The macular pathology occurred in the setting of vitreopapillary traction overlying multiple congenital optic nerve abnormalities, including a myelinated nerve fiber layer and a Bergmeister papilla. Following pars plana vitrectomy to alleviate the traction, the patient's macular appearance improved, and his vision slowly recovered to baseline. There are limited reports of congenital optic nerve anomalies associated with vitreopapillary traction and maculopathy among any age group. This report illustrates a pediatric case in which removal of traction on the nerve head by pars plana vitrectomy was the key therapeutic intervention to alleviate the maculopathy.

GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.

Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) is an age-related macular degeneration-like (AMD-like) retinal dystrophy caused by an autosomal dominant R345W mutation in the secreted glycoprotein, fibulin-3 (F3). To identify new small molecules that reduce F3 production in retinal pigmented epithelium (RPE) cells, we knocked-in a luminescent peptide tag (HiBiT) into the endogenous F3 locus that enabled simple, sensitive, and high-throughput detection of the protein. The GSK3 inhibitor, CHIR99021 (CHIR), significantly reduced F3 burden (expression, secretion, and intracellular levels) in immortalized RPE and non-RPE cells. Low-level, long-term CHIR treatment promoted remodeling of the RPE extracellular matrix, reducing sub-RPE deposit-associated proteins (e.g., amelotin, complement component 3, collagen IV, and fibronectin), while increasing RPE differentiation factors (e.g., tyrosinase, and pigment epithelium-derived factor). In vivo, treatment of 8-month-old R345W+/+ knockin mice with CHIR (25 mg/kg i.p., 1 mo) was well tolerated and significantly reduced R345W F3-associated AMD-like basal laminar deposit number and size, thereby preventing the main pathological feature in these mice. This is an important demonstration of small molecule-based prevention of AMD-like pathology in ML/DHRD mice and may herald a rejuvenation of interest in GSK3 inhibition for the treatment of retinal degenerative diseases, including potentially AMD itself.

Optical coherence tomography angiography findings in high myopia

Background Optical coherence tomography angiography (OCTA) is a sophisticated ophthalmic imaging technique, enables us to obtain images of blood vessels and blood flow at different levels of the retina and choroid without the use of contrast. Therefore, its potential application could be useful in the early detection of retinal vascular and macular pathologies and to recognize the pathogenesis of various ophthalmic diseases. Aim In this study, OCTA was utilized to detect the macular changes in eyes with high myopia. Patients and methods This cross-sectional study was carried out at the Department of Ophthalmology of Menoufia University Hospital according to the Helsinki Declaration and the Code of Ethics for Human Research of the World Medical Association and after obtaining approval of the institutional review board (IRB) 10/2022 OPHT 32. A total of 152 eyes of the study participants were included in this study and were divided into group A, which includes 76 eyes of highly myopic participants (>−6 D), and group B includes 76 eyes of nonmyopic (emmetropic) participants. Result In our study, there was a high statistically significant difference between the studied groups as regards axial length. In group A, it was 27.26±0.74 mm, while in group B, it was 23.14±0.73 mm (P<0.001). Regarding the comparison between studied cases according to the superficial and deep vascular density (SVD and DVD), there was a statistically significant difference between the studied groups. As regards overall SVD in group A, it was 46.48±4.78 while in group B, it was 51.78±2.8 (P<0.001). Meanwhile, the overall DVD in group A was 56.67±3.98, while in group B was 58.76±2.27 (P<0.001). Conclusion In the light of our study, OCTA shows significantly reduced SVD and DVD in eyes with high axial myopia, which could be an important aspect of understanding the natural history and etiology of pathologic myopia.

Optic coherence tomography-angiography – a new technique in the diagnosis and follow-up of the patients with age-related macular degeneration – an overview

Age-related macular degeneration (AMD) is a degenerative, progressive disease, which destroys the central retina. AMD has two main forms - „dry“ and „wet“ (exudative). In order to make the diagnosis of AMD with CNV, apart from ophthalmoscopy, specialized tests are needed - fluorescein angiography (FA), indocyanine angiography, OCT, OCT-angiography (OCT-A). OCTA is a new and non-invasive technology. Compared to the old, well-known techniques for retinal evaluation, it is very precious because of its high resolution and detailed images – which allow early diagnosis and objective monitoring of the lesions in the future. The aim of this review is to describe the principles of function, features of the device and its application in everyday clinical practice in diagnosing patients with macular pathology. A systematic search of the literature, published in the past decade was identified from PubMed and Ovid databases with reference to the Preferred Reporting items for Systematic Review. AMD is a disease that is increasingly socially important because of the aging population in developed countries. The increasing use of OCT-A nowadays suggests new classification systems. The non-invasiveness, the short examination time and the high informativeness that OCT-A brings in relation to AMD requires a deeper study of the methodology and the development of new classifications to facilitate clinical practice.

Exogenous testosterone use and acute central serous chorioretinopathy in a transgender patient

Purpose: To describe the presentation and clinical course of a transgender patient with central serous chorioretinopathy (CSCR) and discuss the role of exogenous testosterone use in CSCR in this patient population. Method: Case report. Results: A 63-year-old transgender male with a history of exogenous testosterone use for over twenty years was referred to retina clinic for evaluation of macular pathology. The patient’s most recent total testosterone levels prior to presentation were 962 and 1,179 ng/dL (normal cisgender male levels for age 60+: 300-720 ng/dL). Fundus imaging revealed subretinal fluid involving the fovea without choroidal neovascularization in the right eye. There was no recent corticosteroid use. The patient’s dose of testosterone was reduced. After four months of observation, the subretinal fluid persisted and was successfully treated with half-fluence photodynamic therapy (PDT). At last follow-up, 15 months after PDT, the patient remained stable without recurrence and the best-corrected visual acuity was at baseline. Conclusion: Exogenous testosterone use with elevated serum testosterone levels may be associated with the development of central serous chorioretinopathy in the transgender patient population. CSCR in these patients might be effectively treated with PDT and testosterone dose reduction. Ophthalmologists should be aware of potential side effects of testosterone supplementation in this patient population, as well as the role of testosterone in CSCR pathophysiology.

Characteristics and type of strabismus associated to macular diplopia. Treatment outcomes

ObjectiveTo study the clinical characteristics of macular diplopia, treatment, and outcome. MethodsRetrospective descriptive study of cases referred to the ocular motility section of a tertiary hospital with diplopia, diagnosed with macular diplopia between 2022−23. The etiology of the macular pathology and the type of associated strabismus were recorded. The result was considered good if the diplopia improved or was eliminated with the medical or surgical treatment. Follow-up time from the onset of diplopia until data collection was recorded. Resultsa total of 19 cases comprised the sample (63.2% women), mean age: 67.16 years. Amblyopia (21.1%), high myopia (47.4%), epirretinal membrane (ERM) (36.8%), neovascular membrane (26.3%), macular hole (10.5%), and lamellar (15.8%), and age macular degeneration (5.3%) were registered. The 47.4% had vertical diplopia, horizontal: 5.3 and 47.4% mixed. The mean horizontal deviation was: 7.3 PD (prism diopters) and vertical: 6.22 PD. Ocular extorsion was observed in 26.3%, and intorsion: 5.3%. Torticollis was present in 15.8%. The treatment consisted of strabismus surgery + Botox (15.8%), strabismus surgery (47.4%), medical treatment with Fresnel prims or Scotch cellophane (36.8%). A 68.4% presented a good result at the end of the study. The mean follow-up was 55.58 months. ConclusionsMisregistration of macular photoreceptors is the most common cause of binocular diplopia in patients with ERM or other macular pathologies. Most complains of vertical or mixed diplopia. Sensorimotor evaluation of these patients should be thorough. Early diagnosis prevents unnecessary prescription of prism glasses. Surgical and/or medical treatment achieves good results in most cases.

Effectiveness of Mp-3 Microperimetric Biofeedback Fixation Training For Low Vision Rehabilitation in Patients Treated With Corticosteroid Ivt in Retinal Vein Occlusions.

The success of fixation training using microperimetric biofeedback (MP-3 MBFT) in the realm of visual rehabilitation for patients with central vision loss caused by macular pathologies is well established. This study aimed to assess the effectiveness and safety of visual rehabilitation with microperimetric biofeedback in consolidating the benefits obtained, with the goal of reducing the need for repeated intravitreal injections (IVT). Specifically, the focus is on the eyes of patients with central vision loss treated with slow-release corticosteroid IVT following retinal venous thrombosis (RVO), aiming to enhance and maintain postoperative efficacy. This retrospective review involved the examination of 44 eyes affected by macular edema due to RVO associated with central vision loss. Patients were divided into two groups, with only one undergoing ten sessions of 10-minute visual rehabilitation with a microperimeter (MP-3 MBFT) after IVT over a period of 20 weeks. All the treated patients demonstrated good tolerance to the procedure, with no reported complications. A comparison of best-corrected visual acuity (BCVA), retinal sensitivity recorded with a microperimeter, and pre-IVT fixation stability revealed statistically significant improvements at the end of the first month after IVT. However, the treatment group continued to exhibit superior and more enduring results at four months post-IV. The synergistic use of MP-3 MBFT rehabilitation after IVT with slow-release corticosteroids has proven particularly effective in improving BCVA and long-term fixation stability. This led to a significant reduction in the number of required IVTs, with no related adverse events. The authors argue that biofeedback utilization represents a noninvasive therapeutic option devoid of contraindications and easy to implement and that it positively contributes to the overall patient experience regarding quality of life in advanced stages of macular diseases.

Sensitivity and specificity of SS-OCT for detecting macular pathologies vs SD-OCT.

To evaluate the sensitivity and specificity of swept-source optical coherence tomography (SS-OCT) biometer compared with the gold standard spectral-domain optical coherence tomography (SD-OCT) for detecting macular pathology in patients with cataract. Eye Centers of Tennessee, Crossville, TN. Prospective, cross-sectional, observational, examiner-masked. The study included 132 participants aged 50 years and older, who underwent precataract surgery work-up. All participants underwent fixation check retinal scans using SS-OCT biometer (IOLMaster 700) as well as full macular scans using Cirrus SD-OCT. 3 independent masked examiners evaluated the scans if they were normal or had a suspected pathology. Different measures of diagnostic accuracy were calculated for 3 examiners. True positive rate (sensitivity) ranged from 71.1% (32/45) to 79.2% (42/53), and false negative rate was between 20.8% (11/53) and 28.9% (13/45) for the 3 examiners. True negative rate (specificity) ranged from 86.8% (59/68) to 94.1% (64/68), and false positive rate was between 5.9 (4/68) and 13.2% (9/68). The fitted receiver operating characteristic area ranged from 0.83 to 0.95. Using retinal SS-OCT biometer scans as a replacement of the dedicated macular SD-OCT for screening or diagnosing macular health would not be appropriate because of its low sensitivity. SS-OCT biometer may potentially fail to identify approximately one-fourth of patients who actually have the disease. Therefore, the final decision on macular health should be based on the gold standard SD-OCT scans. When full macular SD-OCT scans are not accessible, the limited retinal scan information from SS-OCT biometer may still provide useful insights into the macular health.

Características y estrabismos asociados a la diplopía macular. Resultados del tratamiento

ObjectiveTo study the clinical characteristics of macular diplopia, treatment, and outcome. MethodsRetrospective descriptive study of cases referred to the ocular motility section of a tertiary hospital with diplopia, diagnosed with macular diplopia between 2022-23. The etiology of the macular pathology and the type of associated strabismus were recorded. The result was considered good if the diplopia improved or was eliminated with the medical or surgical treatment. Follow-up time from the onset of diplopia until data collection was recorded. ResultsA total of 19 cases comprised the sample (63.2% women), mean age: 67.16 years. Amblyopia (21.1%), high myopia (47.4%), epirretinal membrane (ERM) (36.8%), neovascular membrane (26.3%), macular hole (10.5%), and lamellar (15.8%), and age macular degeneration (5.3%) were registered. The 47.4% had vertical diplopia, horizontal: 5.3 and 47.4% mixed. The mean horizontal deviation was: 7.3 PD (prism diopters) and vertical: 6.22 PD. Ocular extorsion was observed in 26.3%, and intorsion: 5.3%. Torticollis was present in 15.8%. The treatment consisted of strabismus surgery+Botox (15.8%), strabismus surgery (47.4%), medical treatment with Fresnel prims or Scotch cellophane (36.8%). A 68.4% presented a good result at the end of the study. The mean follow-up was 55.58 months. ConclusionsMisregistration of macular photoreceptors is the most common cause of binocular diplopia in patients with ERM or other macular pathologies. Most complains of vertical or mixed diplopia. Sensorimotor evaluation of these patients should be thorough. Early diagnosis prevents unnecessary prescription of prism glasses. Surgical and/or medical treatment achieves good results in most cases.

Optical Coherence Tomography in Inherited Macular Dystrophies: A Review.

Macular dystrophies (MDs) constitute a collection of hereditary retina disorders leading to notable visual impairment, primarily due to progressive macular atrophy. These conditions are distinguished by bilateral and relatively symmetrical abnormalities in the macula that significantly impair central visual function. Recent strides in fundus imaging, especially optical coherence tomography (OCT), have enhanced our comprehension and diagnostic capabilities for MD. OCT enables the identification of neurosensory retinal disorganization patterns and the extent of damage to retinal pigment epithelium (RPE) and photoreceptor cells in the dystrophies before visible macular pathology appears on fundus examinations. It not only helps us in diagnostic retinal and choroidal pathologies but also guides us in monitoring the progression of, staging of, and response to treatment. In this review, we summarize the key findings on OCT in some of the most common MD.

Severity of Disorganization of Retinal Layers and Visual Function Impairment in Diabetic Retinopathy

To evaluate best-corrected visual acuity (BCVA), retina sensitivity (RS), and fixation impairment by microperimetry (MP) due to the presence and severity of disorganization of retinal inner and outer layers (DRIL/DROL) and ischemia in OCT/OCT angiography (OCTA) in diabetic retinopathy (DR). Retrospective case-control study. Seventy-six eyes (65 patients) with DR were analyzed. Major exclusion criteria were: center-involving diabetic macular edema (DME), significant media opacity, nondiabetic macular pathology, and active proliferative DR. Patients with DRIL and DROL within central 3 mm were enrolled as cases. Patients with DR and no retina disorganization were considered as controls. A detailed grading of MP and OCT/OCTA images using Image J software, and specific Image Manipulation Program was applied to colocalize the presence of retina disorganization and RS. Best-corrected visual acuity and RS were correlated with the disorganization of retina layers' characteristics and grading (grade 1-DRIL; grade 2-DROL; grade 3-DROL plus, with involvement of the ellipsoid zone). The same procedure of colocalization was applied to the vascular layers on OCTA using MATLAB. Correlation between BCVA and MP parameters with disorganization of retina layers grading and OCTA parameters. Best-corrected visual acuity, mean RS within 1 mm and central 3 mm (overall RS [oRS]), perfusion density, vessel density, and geometric perfusion deficit in intermediate and deep capillary plexuses were lower in cases versus controls (P < 0.001). Mean RS within 1 mm (21.4 decibels [dB] ± 2.4 vs. 13.8 dB ± 5.4, P= 0.002), oRS (22.0 dB ± 2.1 vs. 14.4 dB ± 4.6, P < 0.001), and BCVA (76.1 ± 7.4 vs. 61.2 ± 20.4 ETDRS letters; P= 0.02), had a significant decrease from grade 1 to grade 3 retina disorganization. Choriocapillaris flow voids (CC-FVs) increased from grade 1 to grade 3 (DROL plus) (P= 0.004). Overall retina sensitivity and CC-FV were identified as significant predictors of retina disorganization grade with an adjusted coefficient of determination, R2= 0.45. Cases had more dense scotomas (P= 0.03) than controls with a positive correlation between the worsening of fixation stability and the severity of DRIL/DROL (P= 0.04). Microperimetry and BCVA documented a reduction in visual function in patients with DR and disorganization of retina layers at different grades, with greater functional impairment when outer retina layers and photoreceptors are involved. The severity of retina disorganization and the presence of ischemia could serve as a potential biomarker of functional impairment. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY IMAGING OF MACULAR PATHOLOGY.

To survey the impact of directional reflectivity on structures within optical coherence tomography images in retinal pathology. Sets of commercial optical coherence tomography images taken from multiple pupil positions were analyzed. These directional optical coherence tomography sets revealed directionally reflective structures within the retina. After ensuring sufficient image quality, resulting hybrid and composite images were characterized by assessing the Henle fiber layer, outer nuclear layer, ellipsoid zone, and interdigitation zone. Additionally, hybrid images were reviewed for novel directionally reflective pathological features. Cross-sectional directional optical coherence tomography image sets were obtained in 75 eyes of 58 patients having a broad range of retinal pathologies. All cases showed improved visualization of the outer nuclear layer/Henle fiber layer interface, and outer nuclear layer thinning was, therefore, more apparent in several cases. The ellipsoid zone and interdigitation zone also demonstrated attenuation where a geometric impact of underlying pathology affected their orientation. Misdirected photoreceptors were also noted as a consistent direction-dependent change in ellipsoid zone reflectivity between regions of normal and absent ellipsoid zone. Directional optical coherence tomography enhances the understanding of retinal anatomy and pathology. This optical contrast yields more accurate identification of retinal structures and possible imaging biomarkers for photoreceptor-related pathology.

Возможности использования интраокулярной коррекции со сложной оптикой у пациентов с эпимакулярным фиброзом

Еpimacular fibrosis (EMF) occupies one of the leading positions in the structure of retinal surgical diseases. Vitreoretinal surgeons often face the necessity to perform combined surgical intervention in patients with native lens. Multifocal IOLs and IOLs with complex optics are strongly contraindicated for implantation in patients with macular pathology. However, not so long ago the ophthalmologic world was presented with an innovative method of presbyopia correction using EDOF IOLs (Extended depth-of-focus). Purpose. To study the use of intraocular correction with complex optics in patients with epimacular fibrosis. Material and methods. 14 patients of different genders with clinically significant EMF and initial cataract were included in the study. Patients underwent combined surgery including phacoemulsification (PEK) with implantation of EDOF IOL (Synthesis+ (Cutting Edge), France) and subsequent standard vitrectomy surgery. All patients underwent standard ophthalmologic examination before surgery and one month after surgical treatment. Results and discussion. We found that the distance vision after one month had a significant increase. Determination of IEP at the middle distance also recorded an increase. We recorded a statistically significant increase in the RPE at close distance visometry, which is probably explained by the elimination of central opacity of the own crystalline lens, preventing the ability of clear focusing of vision in the presence of presbyopic refraction. Keywords: epimacular fibrosis, facovitrectomy, EDOF, presbyopia, cataract, IOL

Динамика анатомических и функциональных показателей после хирургии сквозных макулярных разрывов большого диаметра

Full-thickness macular hole (FTMH) is the macular zone pathology, leading to a significant decrease in visual acuity. According to the literature, classical surgery of FTMH allows to achieve anatomical closure only in 73.3 % of cases. The task of developing a method of surgical treatment of FTMH with the possibility of evaluating its closure intraoperatively is relevant and of strategically important interest for the development of ophthalmic surgery. The purpose of this study is to evaluate the dynamics of functional and anatomical results of large diameter FTMH surgery. Material and methods. A randomized study was conducted on two comparable groups of patients. Surgical treatment of FTMH was performed in both groups, the difference was in the FTMH closure method: in the first group, treatment was carried out according to the proposed method, in the second group, autologous conditioned plasma was used during the surgery. Patients underwent a standard ophthalmological examination, as well as optical coherence tomography of the retina before surgery, 1, 3 and 6 months after surgery. Results and discussion. In the control group, 4 cases of FTMH recurrence were recorded in the postoperative period up to 1 month after surgery. U-shaped closure pattern (Fig. 1) was more often observed in the first group, while in the second group V-shaped closure pattern was more often observed (Fig. 2). Visual acuity 6 months after surgery was higher on average in patients in the first group (p = 0,05). Conclusions. The results obtained indicate a decrease in the risk of recurrence of FTMH, as well as higher visual acuity and close-to-normal retinal histological state in the postoperative period for a period of 6 months when closing the FTMH according to the proposed method. The use of the FTMH closure method under the intraoperative optical coherence tomography control makes it possible to minimize the time of the patient's forced position in the postoperative period, which facilitates its course. Keywords: vitreoretinal surgery, macular hole, optical coherence tomography, autologous conditioned plasma

Explore the possibilities of the artificial intelligence program in the diagnosis of diabetic macular edema, age-related macular degeneration, central serous choriopathy and vitreomacular interface anomalies on the structural optical coherence tomography scans.

Background: macular diseases present a large group of pathological conditions leading to vision loss and poor vision. Early diagnosis of such changes plays an important role in the treatment tactics and comes one of the crucial factors in predicting results.&#x0D; Aims: study the possibilities of the artificial intelligence program in the diagnosis of the macular diseases based on the scans of structural OCT analysis.&#x0D; Materials and methods: the study included patients undergoing examination and treatment at the Federal Medico-Biological Agency Federal Research Clinical Center and the Moscow Regional Research Clinical Institute named after M.F. Vladimirsky. 200 eyes with the macular diseases and also eyes without macular pathology were examined. A comparative clinical analysis of structural OCT scans performed on an RTVue XR 110-2 tomograph was carried out. Retina AI software was used to analyze OCT scans.&#x0D; Results: during the OCT scans analysis various pathological structures of the macular were identified, and then a probable diagnosis was defined. The obtained results were compared with the diagnosis of the ophthalmologists. The sensitivity of the method was 95.16%; specificity - 97.76%; accuracy - 97.38%.&#x0D; Conclusions: Retina.AI allows ophthalmologists to successfully perform automated analysis of the OCT scans and identify various pathological conditions of the eye fundus.

QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration

DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype–environment interaction in retina.

High Dynamic Range Image Processing for Retinal Color Fundus Photography.

Color fundus photography is an important imaging modality that is currently limited by a narrow dynamic range. We describe a post-image processing technique to generate high dynamic range (HDR) retinal images with enhanced detail. This was a retrospective, observational case series evaluating fundus photographs of patients with macular pathology. Photographs were acquired with three or more exposure values using a commercially available camera (Topcon 50-DX). Images were aligned and imported into HDR processing software (Photomatix Pro). Fundus detail was compared between HDR and raw photographs. Sixteen eyes from 10 patients (5 male, 5 female; mean age 59.4 years) were analyzed. Clinician graders preferred the HDR image 91.7% of the time (44/48 image comparisons), with good grader agreement (81.3%, 13/16 eyes). HDR fundus imaging is feasible using images from existing fundus cameras and may be useful for enhanced visualization of retinal detail in a variety of pathologic states. [Ophthalmic Surg Lasers Imaging Retina 2024;55:263-269.].

Aniridia cohort data from the Schwiete center

In congenital aniridia, there is malformation of almost all eye segments. In addition, endocrinologic, metabolic and central nervous systems diseases may be present. The most common ophthalmic signs in congenital aniridia are AAK, iris malformation, cataract and macular hypoplasia. Between 556 eyes of 286 subjects (20.1 ± 20.1 years; 45.5% males), there was nystagmus in 518 (93.7%) eyes, strabismus in 327 (58.8%) eyes. There was iris malformation with atypical coloboma in 34 eyes (6.1%), more than 6 clock hours of iris remnants in 61 eyes (10.9%), less than 6 clock hours of iris remnants in 96 eyes (17.2%), and complete aniridia in 320 (57.5%) eyes. The patients were graded according to the following aniridia‐associated keratopathy (AAK) stages: Stage 0 (96 eyes (17.2%), no keratopathy), Stage 1 (178 eyes (32.0%)), Stage 2 (107 eyes (19.2%)), Stage 3 (67 eyes (12.0%)), Stage 4 (62 eyes (11.1%)), Stage 5 (45 eyes (8.0%)). There was clear lens in 127 (22.8%), cataract in 224 (40.2%), subluxated lens in 9 (1.6%), pseudophakia in 129 (23.2%), aphakia in 32 (5.7%) eyes. There was secondary glaucoma in 307 (55.5%), macular hypoplasia in 395 (71.4%) and congenital optic nerve head pathology in 223 (40.3%) eyes. The iris malformation type may indicate future expression of AAK, cataract and glaucoma development and it is correlated with congenital optic nerve head and macular pathology. Our registry will support further detailed longitudinal analysis of ophthalmic and systemic diseases of aniridia subjects during long‐term follow‐up.

Increased secretory autophagy in retinal pigment epithelial cells of the 5xFAD mice

Purpose: Disturbed proteostasis and oxidative stress have a key role in Alzheimer's disease and age‐related macular degeneration pathology. Constant oxidative stress and disturbed proteostasis lead to intracellular protein aggregation and possibly the activation of secretory autophagy. In this study we assessed the oxidative stress and secretory autophagy related biomarker changes in the retinal pigment epithelium (RPE) of the 5xFAD mice model expressing abundant levels of the human beta‐amyloid.Methods: The eyes of 3‐, 6‐ and 12‐month‐old WT (n = 5) and 5xFAD (n = 5) mice were enucleated, paraffin fixed and examined by immunomicroscopy. The paraffin sections were immunostained for beta‐amyloid and the key secretory autophagy markers Sec22b, TRIM16, galectin 8, IL‐1β, HMGB1 and ferritin. Moreover, the sections were stained for oxidative stress marker 4‐HNE and antioxidant enzyme catalase. Protein degradation related markers ubiquitin (Ub) and SQSTM1/p62 were analysed from 6‐ and 12‐months timepoints.Results: Immunohistochemistry analysis revealed that the oxidative stress and protein degradation related markers were upregulated in the RPE of 6 and 12‐months old 5xFAD mice suggesting presence of oxidative stress and protein aggregation. TRIM16 and galectin 8 were increased in the RPE of the 6‐ and 12‐months old 5xFAD mice, while the increased expression of Sec22b was observed in 3‐ and 6‐months timepoint. IL‐1β, HMGB1 and ferritin were accumulated at the basal side of the RPE cells/Bruch's membrane in 6‐months old 5xFAD mice. The high accumulation of beta‐amyloid was detected in drusen like structures. Electrophysiological analysis revealed decreased scotopic and photopic signalling compared to WT mice.Conclusions: 5xFAD mouse model seems to be a good model to study protein aggregation and activation of the secretory autophagy in response to degenerative retina processes.

Macular Anatomy and Abnormalities in Neurofibromatosis Type 2

Purpose: To describe macular anatomy and abnormalities on Spectral-Domain Optical Coherence Tomography (SD-OCT) in a large series of patients with Neurofibromatosis Type 2 (NF2). Methods: Retrospective review of all consecutive patients with NF2. Results: A total of 166 eyes in 83 patients with NF2 were identified from February 2014 to May 2015. Macular SD-OCT was available for 124 eyes (75%). Isolated epiretinal membrane (ERM) was diagnosed in 52% of patients (n=43) with bilateral ERM in 15 cases. ERM was commonly fine (64%), non-retractile (90%), extra-foveolar (90%), discontinuous (78%) and without posterior vitreous detachment (93%). Combined Hamartoma of the Retina and Retinal Pigmented Epithelium (CHRRPE) was seen in 12% of patients (n=10); three of which were bilateral. Additional OCT anomalies identified include Congenital Hypertrophy of Retinal Pigment Epithelium (CHRPE), internal limiting membrane irregularities, inner retinal tufts, serpentine-like extensions into the vitreoretinal interface, focal alterations of inner retinal lamination and infiltration of the posterior vitreous cortex. All retinal anomalies identified suggest pathological involvement of Müller cells. Conclusion: Our series underscores the utility of macular SD-OCT in patients with NF2. While ERM and vitreoretinal interface abnormalities are the most common macular pathology identified in NF2, all SD-OCT pathology suggests Muller cell involvement.