Areas Of Atrophy Research Articles

Macular Findings of Patients on Pentosan Polysulfate Sodium.

In 2018, a unique maculopathy associated with chronic pentosan polysulfate sodium (PPS) use for the treatment of interstitial cystitis (IC) was described, where the authors detailed macular retinal pigment epithelial abnormalities in six patients. In this paper, a retrospective study of a larger patient pool at one large tertiary retina practice was undertaken to evaluate patients taking PPS and their macular findings. A retrospective chart review was performed on all patients presenting to a single large retina practice between 2011 and 2019. Patient's macular diagnosis, findings, optical coherence tomography scans, and macular auto-fluorescent scans were assessed. This project was Institutional Review Board (IRB) approved by the St Luke's Hospital IRB board (St Louis, MO, USA). Fifty-five patients were identified as taking PPS for IC. Fifty-three patients were found to have a diagnosis consistent with changes attributable to known macular diseases to include macular degeneration and pattern dystrophies. Two (4%) of fifty-five patients had macular findings suggestive of PPS toxicity. The first was a 58-year-old female with subtle retinal pigment epithelium (RPE) deposits on optical coherence tomography that exhibited hyper-autofluorescence. The second was a 72-year-old female with 14 years of PPS use who exhibited RPE excrescences and parafoveal areas of atrophy. Pentosan polysulfate sodium may be the cause of macular findings in a small percentage of patients referred to a tertiary retina practice. Although causation of macular changes with PPS use has yet to be elucidated, clinicians should be aware of this possibility when assessing patients with atypical macular findings. Future longitudinal studies are necessary to evaluate a definitive relationship. This paper should remind all clinicians of the importance of a throughout review of the patient's medication list as novel toxicities may become apparent years after initial FDA trials. The strength of this study is the larger patient population compared to earlier studies, and the main weaknesses include the retrospective nature of the study, lack of family and genetic testing, and lack of multimodal imaging for all patients.

Central retinal vascular trunk deviation in unilateral normal-tension glaucoma.

To investigate whether the position of the central retinal vascular trunk (CRVT), as a surrogate of lamina cribrosa (LC) offset, was associated with the presence of glaucoma in normal-tension glaucoma (NTG) patients. The position of the CRVT was measured as the deviation from the center of the Bruch's membrane opening (BMO), as delineated by spectral-domain optical coherence tomography imaging. The offset index was calculated as the distance of the CRVT from the BMO center relative to that of the BMO margin. The angular deviation of CRVT was measured with the horizontal nasal midline as 0° and the superior location as a positive value. The offset index and angular deviation were compared between glaucoma and fellow control eyes within individuals. NTG eyes had higher baseline intraocular pressure (P = 0.001), a larger β-zone parapapillary atrophy area (P = 0.013), and a larger offset index (P<0.001). In a generalized linear mixed-effects model, larger offset index was the only risk factor of NTG diagnosis (OR = 31.625, P<0.001). A generalized estimating equation regression model revealed that the offset index was larger in the NTG eyes than in the control eyes for all ranges of axial length, while it was the smallest for the axial length of 23.4 mm (all P<0.001). The offset index was larger in the unilateral NTG eyes, which fact is suggestive of the potential role of LC/BMO offset as a loco-regional susceptibility factor.

Altered network stability in progressive supranuclear palsy

The clinical syndromes of Progressive Supranuclear Palsy (PSP) may be mediated by abnormal temporal dynamics of brain networks, due to the impact of atrophy, synapse loss and neurotransmitter deficits. We tested the hypothesis that alterations in signal complexity in neural networks influence short-latency state transitions. Ninety-four participants with PSP and 64 healthy controls were recruited from two independent cohorts. All participants underwent clinical and neuropsychological testing and resting-state functional MRI. Network dynamics were assessed using hidden Markov models and neural signal complexity measured in terms of multiscale entropy. In both cohorts, PSP increased the proportion of time in networks associated with higher cognitive functions. This effect correlated with clinical severity as measured by the PSP-rating-scale, and with reduced neural signal complexity. Regional atrophy influenced abnormal brain-state occupancy, but abnormal network topology and dynamics were not restricted to areas of atrophy. Our findings show that the pathology of PSP causes clinically relevant changes in neural temporal dynamics, leading to a greater proportion of time in inefficient brain-states.

Didanosine-induced Retinopathy: New Insights with Long-term Follow-up

ABSTRACT Introduction Didanosine is an adenosine analog, part of the nucleoside reverse-transcriptase inhibitor family. Since the description of didanosine-induced retinopathy in the early 1990s, little is known about the progression of this toxic retinopathy and the putative underlying mitochondrial defect. Objectives We report long-term follow-up for cases of didanosine-induced retinopathy and discuss a new hypothesis for pathophysiology based on the alteration of endogenous adenosine on the photoreceptor outer segment turnover and phagocytosis by the retinal pigment epithelium. Methods Ophthalmic data from six cases (12 eyes) of didanosine-induced retinopathy from a single institution were retrospectively analyzed. Results All patients displayed bilateral retinal alterations in the mid-periphery. Despite didanosine discontinuation, patients with advanced areas of patchy chorioretinal atrophy appeared to have a faster progression than those with limited lesions. Full-field electroretinogram revealed generalized rod-cone dysfunction in most cases that remained stable over time. Conclusion We propose new guidelines including early screening and long-term observations.

Retro mode illumination for detecting and quantifying the area of geographic atrophy in non-neovascular age-related macular degeneration.

To evaluate the ability of retro mode illumination imaging for quantifying atrophy compared to confocal color fundus photography (c-CFP), green light fundus autofluorescence (G-FAF), blue light fundus autofluorescence (B-FAF) using the scanning laser ophthalmoscope (SLO) Mirante device by Nidek (Nidek Co., Ltd, Gamogori, Japan). Eyes with clinical evidence of geographic atrophy (GA) associated with non-neovascular age-related macular degeneration, evaluated at the Doheny Eye Centers-UCLA and Hospital Sacco Milan, were included in this prospective, cross-sectional study. All eyes were imaged with multiple retinal imaging modalities using the SLO Nidek Mirante device: c-CFP, G-FAF, B-FAF, retro mode illumination deviated-right (RMDR), and deviated-left (RMDL). Masked graders measured the GA lesion on each modality and inter-modality and inter-grader repeatability were assessed. The mean (SD) area of GA measured 9.76 (3.82) mm2, 9.75 (3.91) mm2, 9.76 (3.92) mm2, 9.82 (3.87) mm2, and 9.81 (3.86) mm2 using c-CFP, G-FAF, B-FAF, RMDR, and RMDL, respectively (p = 0.2). Inter-modality correlation was high (Pearson's r > 0.9 and p < 0.0001). Agreement between graders was excellent for all modalities. Retro mode imaging demonstrated good agreement for measuring GA compared to other imaging modalities, with a high level of repeatability. Given that retro mode imaging uses infrared light and is comfortable, it may prove to be a useful tool for the assessment of GA in the clinic.

Spectral and lifetime resolution of fundus autofluorescence in advanced age-related macular degeneration revealing different signal sources.

To determine the fundus autofluorescence (FAF) lifetimes and spectral characteristics of individual drusen and hyperpigmentation independent of those with retinal pigment epithelium (RPE) in geographic atrophy (GA) areas in late-stage age-related macular degeneration (AMD). Three consecutive patients with complete RPE and outer retinal atrophy (cRORA) exhibiting drusen that were calcified or associated with hyperpigmentation were investigated with multimodal non-invasive ophthalmic imaging including colour fundus photography (CFP), optical coherence tomography (OCT), near-infrared reflectance (NIR), blue FAF and fluorescence lifetime imaging ophthalmoscopy (FLIO). Fluorescence lifetimes were measured in two spectral channels (short-wavelength spectral channel (SSC): 500-560 nm and long-wavelength spectral channel (LSC): 560-720 nm). Drusen lacking RPE coverage, as confirmed by CFP and OCT, had longer FAF lifetimes than surrounding cRORA by 127 ± 66 ps (SSC) and 113 ± 48 ps (LSC, both p = 0.008 in Wilcoxon test, N = 9) and by 209 ± 100 ps (SSC) and 121 ± 56 ps (LSC, p < 0.001, N = 14) in two patients. Hyperpigmentation in CFP in a third patient shows strong FAF with prolonged lifetimes. In the SSC, persistent FAF was found inside cRORA. A crescent-shaped hyperfluorescence in an area of continuous RPE but lacking outer retina was seen in one eye with a history of anti-VEGF treatment. Short-wavelength fluorescence in cRORA points to fluorophores beyond RPE organelles. Fluorescence properties of drusen within cRORA differ from invivo drusen covered by RPE. These limited findings from three patients give new insight into the sources of FAF that can be further elucidated in larger cohorts.

Self-Supervised Feature Learning and Phenotyping for Assessing Age-Related Macular Degeneration Using Retinal Fundus Images

Diseases such as age-related macular degeneration (AMD) are classified based on human rubrics that are prone to bias. Supervised neural networks trained using human-generated labels require labor-intensive annotations and are restricted to specific trained tasks. Here, we trained a self-supervised deep learning network using unlabeled fundus images, enabling data-driven feature classification of AMD severity and discovery of ocular phenotypes. Development of a self-supervised training pipeline to evaluate fundus photographs from the Age-Related Eye Disease Study (AREDS). One hundred thousand eight hundred forty-eight human-graded fundus images from 4757 AREDS participants between 55 and 80 years of age. We trained a deep neural network with self-supervised Non-Parametric Instance Discrimination (NPID) using AREDS fundus images without labels then evaluated its performance in grading AMD severity using 2-step, 4-step, and 9-step classification schemes using a supervised classifier. We compared balanced and unbalanced accuracies of NPID against supervised-trained networks and ophthalmologists, explored network behavior using hierarchical learning of image subsets and spherical k-means clustering of feature vectors, then searched for ocular features that can be identified without labels. Accuracy and kappa statistics. NPID demonstrated versatility across different AMD classification schemes without re-training and achieved balanced accuracies comparable with those of supervised-trained networks or human ophthalmologists in classifying advanced AMD (82% vs. 81-92% or 89%), referable AMD (87% vs. 90-92% or 96%), or on the 4-step AMD severity scale (65% vs. 63-75% or 67%), despite never directly using these labels during self-supervised feature learning. Drusen area drove network predictions on the 4-step scale, while depigmentation and geographic atrophy (GA) areas correlated with advanced AMD classes. Self-supervised learning revealed grader-mislabeled images and susceptibility of some classes within more granular AMD scales to misclassification by both ophthalmologists and neural networks. Importantly, self-supervised learning enabled data-driven discovery of AMD features such as GA and other ocular phenotypes of the choroid (e.g., tessellated or blonde fundi), vitreous (e.g., asteroid hyalosis), and lens (e.g., nuclear cataracts) that were not predefined by human labels. Self-supervised learning enables AMD severity grading comparable with that of ophthalmologists and supervised networks, reveals biases of human-defined AMD classification systems, and allows unbiased, data-driven discovery of AMD and non-AMD ocular phenotypes.

Gyrate Atrophy

Gyrate Atrophy is an autosomal recessively inherited rare disease of the choroid and retina. Deficiency of ornithine aminotransferase enzyme (OAT) leads to 10 to 20 times ornithine levels in plasma which is thought to be the cause for the ocular findings. OAT gene is located on the tenth chromosome and when a mutation occurs OAT enzyme activity is decreased in the body. In the first decade, areas of chorioretinal atrophy are seen in the mid-peripheral retinal areas. In the progressing years, the macula may be involved and myopia is an accompanying feature]. Patients initially describe night vision problems and progressive visual field defects leading to central vision loss and blindness later on in the disease. Diagnosis is evident with clinical findings and elevated ornithine levels in plasma and is confirmed with OAT enzyme immune assay. Treatment is dietary modification and treatment of complications that may develop in the retina. GA is reported in diverse ethnic populations and in many sites around the World. Finland is the most reported country (1/50,000). It is very rare in Turkey.

Scleral rupture during micro-incision vitrectomy surgery for primary rhegmatogenous retinal detachment - A case report

Scleral rupture during 23-gauge pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment, without known predisposing factors, is a rare but catastrophic complication. Scleral rupture in our patient developed in superotemporal quadrant corresponding to the area of chorioretinal atrophy in retina. Prompt suturing of scleral rupture, usage of perfluoro-N-octane (PFO) as short-term endo-tamponade, and removal of epiretinal membrane (ERM) under silicone oil (SO) were the major contributing factors leading to successful outcome. High index of suspicion should be kept for any chorioretinal atrophic patches and sclera corresponding to these areas should be carefully examined for any pathosis.

Bone Ring Autogenous Graft and Immediate Implant Reconstruction in Atrophic Posterior Mandibular Area

Purpose: to evaluate clinical and radiographic outcome of bone ring grafting technique with immediate implant placement in fresh extraction socket in mandibular posterior area. Patients and methods: Clinical study was conducted on six patients, suffer from deficiency in vertical height at posterior mandibular area. Extraction and immediate implant reconstruction with symphyseal bone grafting in one-stage procedure. All steps of harvesting by trephine bur, implant osteotomy and placement within the socket were guided by computerized surgical stent for donor and recipient sites. Platelet Rich Fibrin (PRF) membrane was prepared to cover the implant at suture line. Patients were followed up clinically and radiographically by Cone Beam Computed Tomography (CBCT) at immediate,3 and 6 months postoperatively to evaluate the implant site and vertical bone height changes. Results: One successful case out of six showed excellent soft tissue healing with implant stability. Clinically one case showed sever infection at 2 weeks postoperatively with looseness of implant. Dehiscence and pain were found in 83.3% of the cases. Four cases had mild pain and one case suffered from severe pain, edema was mild in the majority of patients, numbness was found in 4 cases with 66.7%. CBCT results showed significant decrease in 3D dimensions of vertical bone height from immediate postoperative to 6 months with percentage of resorption (Buccally37.49±12.14, Lingually36.12±12.04, Mesially 39.55±15.05 and Distally10.92±0.76). Conclusion: From our study, Bone ring augmentation technique for fresh defective sockets with immediate implants at posterior mandibular area achieved low success rate, long procedure time and donor site morbidity.

Treatment of striae distensae: recent conceptions

Stretch marks (striae distensae) are linear areas of cutaneous atrophy that appear in regions of greatest stretch of the skin. Their formation is a complex multifactorial process, its etiopathogenesis has not been fully understood yet. Aesthetic correction of stretch marks is an urgent problem of modern dermatocosmetology due to their widespread prevalence and pronounced negative impact on the patient’s quality of life. The aim of this paper was to provide a review of the literature on current reported treatment options for stretch marks. The principles of the effect of various methods of treatment, their classification and data from clinical trials are considered.

To Evaluate the Inhibition Leukemia Cell Effect of Haploidentical Spleen in Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation

[Objective] To evaluate the inhibition leukemia cell effect of haploidentical spleen in nonmyeloablative allogeneic hematopoietic stem cell transplantation.[Method] Take C57/BL/6 inbred mice (B6 mice) of 8-12 weeks as donor rats. Extract their bone marrow and spleen cells. P815 cells were as mast cell tumor cells (leukemia cells) of DBA/2 mice. The first generation 6D2F1 rats (F1 rats) were as recipients who were hybridized by C57/BL/6 mice and DBA/2 mice. F1 rats were made with the nonmyeloablative conditioning regimen CTX 300mg/m2 /d intraperitoneal injection on the hematopoietic stem cell transplantation -5d, -4d, -3d. In day 0, Group A-D were infused spleen + bone marrow cells +P815 cells; bone marrow cells + P815 cells; P815 cells and RPMI1640 culture medium respectively to compare the status of the mice blood, aGVHD and the pathological tumor infiltration of skin, liver and colon.[Results] 1. aGVHD score: the aGVHD score of group A was 2-4 who were alive on the 14th day after transplantation. The death occured on the fifteenth day. The clinical score was 6 on the twenty-sixth day for the 2 alive mice, and the rest of the mice were scored at 0-3. In group B, the mice began to die on the sixth day, and only 1 survived at the end of the thirtieth day. Group C died all in eighteenth days. 2. Pathological observation: the liver inflammatory cell infiltration in Group A, portal area of liver cell atrophy and necrosis of hepatic portal area and central veins focal infiltration of tumor cells or a small amount of infiltration could be observed. In Group B, the number of hepatocytes in the liver of the mice was decreased, and the infiltration of the tumor in the liver sinus was diffuse.[Conclusion] In nonmyeloablative allogeneic hematopoietic stem cell transplantation, the MHC haploidentical spleen may inhibit leukemia cell effect.[Discussion] Group A, compared with Group B and C, showed the aGVHD effect, as well as GVL effect. The spleen of haploidentical nonmyeloablative hematopoietic stem cell transplantation may make chimerism of immune cells of B6 mice and hematopoietic immune cells of F1 mice. The activated lymphocyte of the spleen of B6 mice and F1 mice could identify, monitor, inhibit and kill P815 cells. In nonmyeloablative allogeneic hematopoietic stem cell transplantation, the MHC haploidentical spleen may inhibit leukemia cell effect. DisclosuresNo relevant conflicts of interest to declare.

Differential and Altered Spatial Distribution of Complement Expression in Age-Related Macular Degeneration.

PurposeDysregulation of the alternative complement pathway is a major pathogenic mechanism in age-related macular degeneration. We investigated whether locally synthesized complement components contribute to AMD by profiling complement expression in postmortem eyes with and without AMD.MethodsAMD severity grade 1 to 4 was determined by analysis of postmortem acquired fundus images and hematoxylin and eosin stained histological sections. TaqMan (donor eyes n = 39) and RNAscope/in situ hybridization (n = 10) were performed to detect complement mRNA. Meso scale discovery assay and Western blot (n = 31) were used to measure complement protein levels.ResultsThe levels of complement mRNA and protein expression were approximately 15- to 100-fold (P < 0.0001–0.001) higher in macular retinal pigment epithelium (RPE)/choroid tissue than in neural retina, regardless of AMD grade status. Complement mRNA and protein levels were modestly elevated in vitreous and the macular neural retina in eyes with geographic atrophy (GA), but not in eyes with early or intermediate AMD, compared to normal eyes. Alternative and classical pathway complement mRNAs (C3, CFB, CFH, CFI, C1QA) identified by RNAscope were conspicuous in areas of atrophy; in those areas C3 mRNA was observed in a subset of IBA1+ microglia or macrophages.ConclusionsWe verified that RPE/choroid contains most ocular complement; thus RPE/choroid rather than the neural retina or vitreous is likely to be the key site for complement inhibition to treat GA or earlier stage of the disease. Outer retinal local production of complement mRNAs along with evidence of increased complement activation is a feature of GA.

Comparing Fluorescence Lifetime Imaging Ophthalmoscopy in Atrophic Areas of Retinal Diseases.

PurposeFluorescence lifetime imaging ophthalmoscopy (FLIO) is a non-invasive imaging modality to investigate the human retina. This study compares FLIO lifetimes in different degenerative retinal diseases.MethodsIncluded were eyes with retinal pigment epithelium (RPE) and/or photoreceptor atrophy due to Stargardt disease (n = 66), pattern dystrophy (n = 18), macular telangiectasia type 2 (n = 49), retinitis pigmentosa (n = 28), choroideremia (n = 26), and geographic atrophy (n = 32) in age-related macular degeneration, as well as 37 eyes of 37 age-matched healthy controls. Subjects received Heidelberg Engineering FLIO, autofluorescence intensity, and optical coherence tomography imaging. Amplitude-weighted mean FLIO lifetimes (τm) were calculated and analyzed.ResultsRetinal FLIO lifetimes show significant differences depending on the disease. Atrophic areas in geographic atrophy and choroideremia showed longest mean FLIO lifetimes. τm values within areas of RPE and outer nuclear layer atrophy were significantly longer than within areas with preserved outer nuclear layer (P < 0.001) or non-atrophic areas (P < 0.001).ConclusionsFLIO is able to contribute additional information regarding differences in chronic degenerative retinal diseases. Although it cannot replace conventional autofluorescence imaging, FLIO adds to the knowledge in these diseases and may help with the correct differentiation between them. This may lead to a more in-depth understanding of the pathomechanisms related to atrophy and types of progression.Translational RelevanceDifferences between atrophic retinal diseases highlighted by FLIO may indicate separate pathomechanisms leading to atrophy and disease progression.

Morphological Study of Color Doppler Ultrasound Imaging to Observe the Effect of Ocular Fundus Surgery

High myopia continues to progress and the eye axis continues to grow, resulting in mechanical dilatation of the eyeball wall, and with the increase of age, resulting in a variety of myopic fundus pathological changes. Considering that in the late stage of fundus disease, patients can obviously feel the impact of the disease on vision, and ophthalmologists are needed for direct diagnosis, intervention and treatment. The impact of early lesions on vision is relatively weak, and patients can not detect the emergence of these lesions in time, which can only be found by fundus survey. Therefore, the automatic detection of early lesions of fundus disease (especially microaneurysms) is not only of great significance for early diagnosis and early treatment of fundus disease, but also a good reference for the detection of other fundus diseases. In this paper, color ultrasound can effectively analyze the origin of fundus diseases. The results showed that with the changes of age, eye axis and posterior sclera shape in high myopia, the area and range of myopic arc and choroidal atrophy arc expanded, the thickness of nerve fiber and choroid became thinner, and the fovea of macula mainly shifted vertically. In addition, it was also found that myopic arc, choroidal atrophic arc area, retinal thickness, nerve fiber thickness, choroidal thickness, vertical distance from macular fovea to optic disc center were correlated with age and eye axis.

Comparison of outcome between percutaneous pedicle screw fixation and the Mini-Open Wiltse Approach with pedicle screw fixation for neurologically intact thoracolumbar fractures: A retrospective study

BackgroundThe purpose of this study was to compare the outcome between percutaneous pedicle screw fixation (PPSF) and the mini-open Wiltse approach with pedicle screw fixation (MWPSF) for neurologically intact thoracolumbar fractures. MethodsFrom January 2017 to January 2019, ninety-four patients with neurologically intact thoracolumbar fractures were included in this study. In this retrospective study, forty-nine patients were operated with the PPSF and forty-five patients received MWPSF. The clinical information, surgery-related results and radiographic outcome were collected and compared between the two groups. ResultsThere was no significant difference between the two groups in total length of incisions, blood loss, post-operative hospitalization time, visual analog scale (VAS) score and Oswestry disability index (ODI) score. There was also no significant difference in the accuracy rate of pedicle screw placement between two groups; however, the facet joint violation (FJV) was significantly higher in the PPSF group. The atrophic area of multifidus muscle in the PPSF group is significantly larger than that in the MWPSF group and the operative time of MWPSF group was shorter than that in the PPSF group. Meanwhile, the PPSF group obtaining significantly more cumulative exposure to radiation (p < 0.001). The result of vertebral body angle (VBA), Cobb's angle and AVH rate in the MWPSF group were significantly better than those in the PPSF group at the last post-operative follow-up. ConclusionsBoth minimally invasive treatment techniques (PPSF and MWPSF) are safe and effective in treatment of neurologically intact thoracolumbar fractures. Nevertheless, our results indicate that MWPSF may be a better choice for neurologically intact thoracolumbar fractures, since it protects multifidus muscle, and decreases facet joint violation, operation time, as well as radiation exposure. In addition, MWPSF was associated with better reduction of kyphosis.

Gordon Holmes syndrome – first time diagnosed in Croatia

We present a 38-year-old woman with clinical presentation of ataxia, cognitive impairment, and secondary amenorrhea with remarkable brain hyperintensities on brain magnetic resonance imaging (MRI). Clinical symptoms began at the age of 20 years with the development of secondary amenorrhea, instability, and cognitive dysfunction. Although this set of medical symptoms of ataxia, primary/secondary amenorrhea due to hypogonadotropic hypogonadism, and cognitive impairment are known as Gordon Holmes syndrome, such has not been described in Croatia so far. Because of this, the patient was unsuccessfully diagnostically investigated in various neurological institutions on different neurodegenerative diseases, primarily based on ataxia, cognitive impairment, and remarkable brain hyperintensities on brain MRI. We started to analyze a large group of possible genetically triggered autosomal-recessive degenerative ataxias, and noticed compatibility of clinical symptoms: cerebellar ataxia, cognitive impairment, and hypogonadotropic hypogonadism, along with brain MRI changes characterized with significant subcortical white matter, thalamic, and brain steam confluent patchy areas of hyperintensity and cerebellar atrophy, that constitute a syndrome caused by ATM RNF216 gene mutation, Gordon Holmes syndrome (GHS). Genetic analysis in Variantyx laboratory in the USA performing whole-exome sequencing showed compound heterozygous for RNF 216 mutation, which confirmed the diagnosis of GHS, for the first time diagnosed in Croatia.

Imaging Features by Machine Learning for Quantification of Optic Disc Changes and Impact on Choroidal Thickness in Young Myopic Patients.

Purpose: To construct quantifiable models of imaging features by machine learning describing early changes of optic disc and peripapillary region, and to explore their performance as early indicators for choroidal thickness (ChT) in young myopic patients.Methods: Eight hundred and ninety six subjects were enrolled. Imaging features were extracted from fundus photographs. Macular ChT (mChT) and peripapillary ChT (pChT) were measured on swept-source optical coherence tomography scans. All participants were divided randomly into training (70%) and test (30%) sets. Imaging features correlated with ChT were selected by LASSO regression and combined into new indicators of optic disc (IODs) for mChT (IOD_mChT) and for pChT (IOD_pChT) by multivariate regression models in the training set. The performance of IODs was evaluated in the test set.Results: A significant correlation between IOD_mChT and mChT (r = 0.650, R2 = 0.423, P < 0.001) was found in the test set. IOD_mChT was negatively associated with axial length (AL) (r = −0.562, P < 0.001) and peripapillary atrophy (PPA) area (r = −0.738, P < 0.001) and positively associated with ovality index (r = 0.503, P < 0.001) and torsion angle (r = 0.242, P < 0.001) in the test set. Every 1 × 10 μm decrease in IOD_mChT was associated with an 8.87 μm decrease in mChT. A significant correlation between IOD_pChT and pChT (r = 0.576, R2 = 0.331, P < 0.001) was found in the test set. IOD_pChT was negatively associated with AL (r = −0.478, P < 0.001) and PPA area (r = −0.651, P < 0.001) and positively associated with ovality index (r = 0.285, P < 0.001) and torsion angle (r = 0.180, P < 0.001) in the test set. Every 1 × 10 μm decrease in IOD_pChT was associated with a 9.64 μm decrease in pChT.Conclusions: The study introduced a machine learning approach to acquire imaging information of early changes of optic disc and peripapillary region and constructed quantitative models significantly correlated with choroidal thickness. The objective models from fundus photographs represented a new approach that offset limitations of human annotation and could be applied in other areas of fundus diseases.

Perifoveal Chorioretinal Atrophy after Subretinal Voretigene Neparvovec-rzyl for RPE65-Mediated Leber Congenital Amaurosis

To report an anatomic change following subretinal injection of voretigene neparvovec-rzyl (VN) for RPE65-mediated Leber congenital amaurosis. Multicenter, retrospective chart review. Patients who underwent subretinal VN injection at each of 4 participating institutions. Patients were identified as having perifoveal chorioretinal atrophy if (1) the areas of atrophy were not directly related to the touch-down site of the subretinal cannula; and (2) the area of atrophy progressively enlarged over time. Demographic data, visual acuity, refractive error, fundus photographs, OCT, visual fields, and full-field stimulus threshold (FST) were analyzed. Outcome measures included change in visual acuity, FST, visual fields, and location of atrophy relative to subretinal bleb position. A total of 18 eyes of 10 patients who underwent subretinal injection of VN were identified as having developed perifoveal chorioretinal atrophy. Eight of 10 patients (80%) developed bilateral atrophy. The mean age was 11.6 years (range, 5-20 years), and 6 patients (60%) were male. Baseline mean logarithm of the minimum angle of resolution visual acuity and FST were 0.82 (standard deviation [SD], 0.51) and-1.3 log cd.s/m2 (SD, 0.44), respectively. The mean spherical equivalent was-5.7 diopters (D) (range,-11.50 to+1.75 D). Atrophy was identifiable at an average of 4.7 months (SD, 4.3) after surgery and progressively enlarged in all cases up to a mean follow-up period of 11.3 months (range, 4-18 months). Atrophy developed within and outside the area of the subretinal bleb in 10 eyes (55.5%), exclusively within the area of the bleb in 7 eyes (38.9%), and exclusively outside the bleb in 1 eye (5.5%). There was no significant change in visual acuity (P= 0.45). There was a consistent improvement in FST with a mean improvement of-3.21 log cd.s/m2 (P < 0.0001). Additionally, all 13 eyes with reliable Goldmann visual fields demonstrated improvement, but 3 eyes (23.1%) demonstrated paracentral scotomas related to the atrophy. A subset of patients undergoing subretinal VN injection developed progressive perifoveal chorioretinal atrophy after surgery. Further study is necessary to determine what ocular, surgical delivery, and vector-related factors predispose to this complication.

Impairments of Photoreceptor Outer Segments Renewal and Phototransduction Due to a Peripherin Rare Haplotype Variant: Insights from Molecular Modeling.

Background: Retinitis pigmentosa punctata albescens (RPA) is a particular form of retinitis pigmentosa characterized by childhood onset night blindness and areas of peripheral retinal atrophy. We investigated the genetic cause of RPA in a family consisting of two affected Egyptian brothers with healthy consanguineous parents. Methods: Mutational analysis of four RPA causative genes was realized by Sanger sequencing on both probands, and detected variants were subsequently genotyped in their parents. Afterwards, found variants were deeply, statistically, and in silico characterized to determine their possible effects and association with RPA. Results: Both brothers carry three missense PRPH2 variants in a homozygous condition (c.910C > A, c.929G > A, and c.1013A > C) and two promoter variants in RHO (c.-26A > G) and RLBP1 (c.-70G > A) genes, respectively. Haplotype analyses highlighted a PRPH2 rare haplotype variant (GAG), determining a possible alteration of PRPH2 binding with melanoregulin and other outer segment proteins, followed by photoreceptor outer segment instability. Furthermore, an altered balance of transcription factor binding sites, due to the presence of RHO and RLBP1 promoter variants, might determine a comprehensive downregulation of both genes, possibly altering the PRPH2 shared visual-related pathway. Conclusions: Despite several limitations, the study might be a relevant step towards detection of novel scenarios in RPA etiopathogenesis.