Sustained Release Formulation of Hydroxypropyl-ß-cyclodextrin Eye Drops Using Xanthan Gum.

Bietti's crystalline dystrophy (BCD) is an autosomal recessive chorioretinal degeneration caused by mutations in the CYP4V2 gene. It is characterized by cholesterol accumulation and crystal-like deposits in the retinas. Hydroxypropyl-ß-cyclodextrin (HP-ß-CyD) exerts therapeutic effects against BCD by reducing lysosomal dysfunction and inhibiting cytotoxicity in induced pluripotent stem cell (iPSC)-RPE cells established from patient-derived iPS cells. However, the ocular retention of HP-ß-CyD is low and needs to be improved. Therefore, this study used a viscous agent to develop a sustained-release ophthalmic formulation containing HP-ß-CyD. Our results suggest that HP-ß-CyD-containing xanthan gum has a considerably higher sustained release capacity than other viscous agents, such as methylcellulose and sodium alginate. In addition, the HP-ß-CyD-containing xanthan gum exhibited pseudoplastic behavior. It was less cytotoxic to human retinal pigment epithelial cells compared with HP-ß-CyD alone. Furthermore, the slow release of HP-ß-CyD from xanthan gum caused a sustained decrease in free intracellular cholesterol. These results suggest that xanthan gum is a useful substrate for the sustained release formulation of HP-ß-CyD, and that HP-ß-CyD-containing xanthan gum has potential as an eye drop for BCD treatment.

Diagnosis of retinal damage using Resnet rescaling and support vector machine (Resnet-RS-SVM): a case study from an Indian hospital.

PURPOSE: This study aims to address the challenge of identifying retinal damage in medical applications through a computer-aided diagnosis (CAD) approach. Data was collected from four prominent eye hospitals in India for analysis and model development. METHODS: Data was collected from Silchar Medical College and Hospital (SMCH), Aravind Eye Hospital (Tamil Nadu), LV Prasad Eye Hospital (Hyderabad), and Medanta (Gurugram). A modified version of the ResNet-101 architecture, named ResNet-RS, was utilized for retinal damage identification. In this modified architecture, the last layer's softmax function was replaced with a support vector machine (SVM). The resulting model, termed ResNet-RS-SVM, was trained and evaluated on each hospital's dataset individually and collectively. RESULTS: The proposed ResNet-RS-SVM model achieved high accuracies across the datasets from the different hospitals: 99.17% for Aravind, 98.53% for LV Prasad, 98.33% for Medanta, and 100% for SMCH. When considering all hospitals collectively, the model attained an accuracy of 97.19%. CONCLUSION: The findings demonstrate the effectiveness of the ResNet-RS-SVM model in accurately identifying retinal damage in diverse datasets collected from multiple eye hospitals in India. This approach presents a promising advancement in computer-aided diagnosis for improving the detection and management of retinal diseases.

OCTDL: Optical Coherence Tomography Dataset for Image-Based Deep Learning Methods.

Optical coherence tomography (OCT) is a non-invasive imaging technique with extensive clinical applications in ophthalmology. OCT enables the visualization of the retinal layers, playing a vital role in the early detection and monitoring of retinal diseases. OCT uses the principle of light wave interference to create detailed images of the retinal microstructures, making it a valuable tool for diagnosing ocular conditions. This work presents an open-access OCT dataset (OCTDL) comprising over 2000 OCT images labeled according to disease group and retinal pathology. The dataset consists of OCT records of patients with Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), Epiretinal Membrane (ERM), Retinal Artery Occlusion (RAO), Retinal Vein Occlusion (RVO), and Vitreomacular Interface Disease (VID). The images were acquired with an Optovue Avanti RTVue XR using raster scanning protocols with dynamic scan length and image resolution. Each retinal b-scan was acquired by centering on the fovea and interpreted and cataloged by an experienced retinal specialist. In this work, we applied Deep Learning classification techniques to this new open-access dataset.

Longitudinal Natural History Study of Visual Function in Bietti Crystalline Dystrophy: Implications for Early Intervention.

Purpose: To delineate the natural history of visual function parameters over time in individuals with Bietti crystalline dystrophy. Methods: This was a single-center retrospective longitudinal cohort study. Participants (n = 29) with a clinical diagnosis of Bietti crystalline dystrophy who harbored two alleles of disease-causing variants of the cytochrome P450 family 4 subfamily V member 2 gene (CYP4V2) were enrolled. Best-corrected visual acuity (BCVA), visual field (VF), and full-field ERG (ffERG) at baseline and their changes during the follow-up period were evaluated. Annual progression rates were calculated using three methods. Results: The mean age at the initial visit was 34.2 ± 7.5 years, with 5.9 ± 3.1 years follow-up. The annual progression rate from the longitudinal analysis using averaged individual progression rates was 0.079 logMAR units for BCVA, 1.14 dB for mean defect (MD) value of VF, and -18.06 µV and -5.45 µV for the b-wave amplitudes of scotopic 3.0 ERG and photopic 3.0 ERG, respectively. Mixed-model linear regression revealed annual progression rates of 0.068 logMAR units, 0.86 dB, -13.29 µV, and -3.75 µV, respectively. Cross-sectional progression rates from visual function versus age at baseline were 0.011 logMAR units, 0.47 dB, -1.85 µV, and -1.07 µV, respectively, which were significantly slower than those from the longitudinal data. Interocular symmetries for the MD values of VF and ffERG were good. Conclusions: Annual BCVA, VF, and ffERG progression rates were rapid, emphasizing the need for regular follow-up and early intervention. The progression rate cannot be inferred accurately from cross-sectional data from patients of different ages.

The socioeconomic epidemiology of inherited retinal diseases in Portugal.

BACKGROUND: Inherited retinal diseases (IRDs) are a group of rare degenerative disorders of the retina that can lead to blindness from birth to late middle age. Knowing the target population and its resources is essential to better plan support measures. The aim of this study was to evaluate the socioeconomic characteristics of regions in Portugal where IRD patients reside to inform the planning of vision aid and rehabilitation intervention measures. RESULTS: This study included 1082 patients from 973 families, aged 3 to 92 years, with a mean age of 44.8 ± 18.1 years. Patients living with an IRD were identified in 190 of the 308 municipalities. According to this study, the estimated IRD prevalence in Portugal was 10.4 per 100,000 inhabitants, and by municipalities, it ranged from 0 to 131.2 per 100,000 inhabitants. Overall, regions with a higher prevalence of IRD have a lower population density (r=-0.371, p < 0.001), a higher illiteracy rate (r = 0.404, p < 0.001) and an overall older population (r = 0.475, p < 0.001). Additionally, there is a lower proportion of doctor per capita (r = 0.350, p < 0.001), higher social security pensions beneficiaries (r = 0.439, p < 0.001), worse water quality for human consumption (r=-0.194, p = 0.008), fewer audiences at the cinema (r=-0.315, p < 0.001) and lower proportion of foreign guests in tourist accommodations (r=-0.287, p < 0.001). CONCLUSION: The number of identified patients with IRD varied between regions. Using data from national statistics (PORDATA), we observed differences in socioeconomic characteristics between regions. Multiple targeted aid strategies can be developed to ensure that all IRD patients are granted full clinical and socioeconomic support.

Serum Biomarkers of Vascular Involvement in Childhood Uveitis.

Purpose: Nonanterior uveitis frequently involves the retinal vasculature; however, no molecular markers associated with the retinal vascular disease are currently known. In this study, we aimed to identify serum biomarker signatures associated with retinal vascular involvement in noninfectious pediatric uveitis. Methods: We performed a 384-plex targeted proteomic analysis of serum samples of 154 noninfectious pediatric uveitis patients diagnosed with nonanterior uveitis (n = 74), idiopathic chronic anterior uveitis (iCAU, n = 36), or juvenile idiopathic arthritis-associated uveitis (JIA-U, n = 44), as well as 22 noninflammatory pediatric controls. Data on retinal vascular involvement (i.e., papillitis, cystoid macular edema, retinal vasculitis, or retinal capillary leakage on optical coherence tomography and/or fluorescein angiography) were used to stratify cases in the nonanterior uveitis group. Results: In the analysis of nonanterior uveitis, we identified nine proteins significantly associated with retinal vascular involvement, including F13B, MYOM3, and PTPN9. These proteins were enriched through pathway enrichment analysis for the coagulation cascade. Comparing cases and controls, we identified 63 differentially expressed proteins, notably proteins involved in platelet biology and complement cascades, which could be primarily attributed to differences in serum proteomes between anterior uveitis and nonanterior uveitis groups. Conclusions: Serum proteins related to the coagulation and complement cascade are associated with retinal vascular involvement in pediatric uveitis patients. Our results indicate involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future. Translational Relevance: Our targeted proteomics analysis in serum of pediatric uveitis patients indicates involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future.

Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing.

OBJECTIVE: Autosomal recessive bestrophinopathy (ARB), a retinal degenerative disease, is characterized by central visual loss, yellowish multifocal diffuse subretinal deposits, and a dramatic decrease in the light peak on electrooculogram. The potential pathogenic mechanism involves mutations in the BEST1 gene, which encodes Ca2+-activated Cl- channels in the retinal pigment epithelium (RPE), resulting in degeneration of RPE and photoreceptor. In this study, the complete clinical characteristics of two Chinese ARB families were summarized. METHODS: Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing was performed on the probands to screen for disease-causing gene mutations, and Sanger sequencing was applied to validate variants in the patients and their family members. RESULTS: Two novel mutations, c.202T>C (chr11:61722628, p.Y68H) and c.867+97G>A, in the BEST1 gene were identified in the two Chinese ARB families. The novel missense mutation BEST1 c.202T>C (p.Y68H) resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of bestrophin-1. Another novel variant, BEST1 c.867+97G>A (chr11:61725867), located in intron 7, might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional regulators. CONCLUSION: Our findings represent the first use of third-generation sequencing (TGS) to identify novel BEST1 mutations in patients with ARB, indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific genes. The novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

Real-Time Temperature-Controlled Retinal Laser Irradiation in Rabbits.

Purpose: Subdamaging thermal retinal laser therapy has the potential to induce regenerative stimuli in retinal diseases, but validated dosimetry is missing. Real-time optoacoustic temperature determination and control could close this gap. This study investigates a first in vivo application. Methods: Two iterations of a control module that were optically coupled in between a continuous-wave commercial laser source and a commercial slit lamp were evaluated on chinchilla rabbits. The module allows extraction of the temperature rise in real time and can control the power of the therapy laser such that a predefined temperature rise at the retina is quickly achieved and held constant. Irradiations with aim temperatures from 45°C to 69°C were performed on a diameter of 200 µm and a heating time of 100 ms. Results: We analyzed 424 temperature-guided irradiations in nine eyes of five rabbits. The mean difference between the measured and aim temperature was -0.04°C ± 0.98°C. The following ED50 values for visibility thresholds could be determined: 58.6°C for funduscopic visibility, 57.7°C for fluorescein angiography, and 57.0°C for OCT. In all measurements, the correlation of tissue effect was higher to the temperature than to the average heating laser power used. Conclusions: The system was able to reliably perform temperature-guided irradiations, which allowed for better tissue effect control than simple power control. This approach could enhance the accuracy, safety, and reproducibility of thermal stimulating laser therapy. Translational Relevance: This study is a bridge between preclinical ex vivo experiments and a pilot clinical study.

Leukocoria Due to Persistent Hyperplastic Primary Vitreous.

This case report discusses a diagnosis of persistent hyperplastic primary vitreous presenting as leukocoria in a boy aged 50 days.

EphB1 causes retinal damage through inflammatory pathways in the retina and retinal Müller cells.

Purpose: To examine whether increased ephrin type-B receptor 1 (EphB1) leads to inflammatory mediators in retinal Müller cells. Methods: Diabetic human and mouse retinal samples were examined for EphB1 protein levels. Rat Müller cells (rMC-1) were grown in culture and treated with EphB1 siRNA or ephrin B1-Fc to explore inflammatory mediators in cells grown in high glucose. An EphB1 overexpression adeno-associated virus (AAV) was used to increase EphB1 in Müller cells in vivo. Ischemia/reperfusion (I/R) was performed on mice treated with the EphB1 overexpression AAV to explore the actions of EphB1 on retinal neuronal changes in vivo. Results: EphB1 protein levels were increased in diabetic human and mouse retinal samples. Knockdown of EphB1 reduced inflammatory mediator levels in Müller cells grown in high glucose. Ephrin B1-Fc increased inflammatory proteins in rMC-1 cells grown in normal and high glucose. Treatment of mice with I/R caused retinal thinning and loss of cell numbers in the ganglion cell layer. This was increased in mice exposed to I/R and treated with the EphB1 overexpressing AAVs. Conclusions: EphB1 is increased in the retinas of diabetic humans and mice and in high glucose-treated Müller cells. This increase leads to inflammatory proteins. EphB1 also enhanced retinal damage in response to I/R. Taken together, inhibition of EphB1 may offer a new therapeutic option for diabetic retinopathy.

Identification of Novel FZD4 Mutations in Familial Exudative Vitreoretinopathy and Investigating the Pathogenic Mechanisms of FZD4 Mutations.

Purpose: The purpose of this study is to report five novel FZD4 mutations identified in familial exudative vitreoretinopathy (FEVR) and to analyze and summarize the pathogenic mechanisms of 34 of 96 reported missense mutations in FZD4. Methods: Five probands diagnosed with FEVR and their family members were enrolled in the study. Ocular examinations and targeted gene panel sequencing were conducted on all participants. Plasmids, each carrying 29 previously reported FZD4 missense mutations and five novel mutations, were constructed based on the selection of mutations from each domain of FZD4. These plasmids were used to investigate the effects of mutations on protein expression levels, Norrin/ß-catenin activation capacity, membrane localization, norrin binding ability, and DVL2 recruitment ability in HEK293T, HEK293STF, and HeLa cells. Results: All five novel mutations (S91F, V103E, C145S, E160K, C377F) responsible for FEVR were found to compromise Norrin/ß-catenin activation of FZD4 protein. After reviewing a total of 34 reported missense mutations, we categorized all mutations based on their functional changes: signal peptide mutations, cysteine mutations affecting disulfide bonds, extracellular domain mutations influencing norrin binding, transmembrane domain (TM) 1 and TM7 mutations impacting membrane localization, and intracellular domain mutations affecting DVL2 recruitment. Conclusions: We expanded the spectrum of FZD4 mutations relevant to FEVR and experimentally demonstrated that missense mutations in FZD4 can be classified into five categories based on different functional changes.

Health state utility values ranges across varying stages and severity of type 2 diabetes-related complications: A systematic review.

INTRODUCTION: Health state utility values (HSUV) for Type 2 diabetes mellitus (T2DM) complications are useful in economic evaluations to determine cost effectiveness of an intervention. However, there is a lack of reference ranges for different severity and stages of individual complications. This study aimed to provide an overview of HSUV decrement ranges for common T2DM complications focusing on different severity and stages of complications. METHOD: A systematic search was conducted in MEDLINE, SCOPUS, WEB OF SCIENCE. (Jan 2000 to April 2022). Included studies for HSUV estimates were from outpatient setting, regardless of treatment types, complication stages, regions and HRQoL instruments. Health Related Quality of Life (HRQoL) outcomes was to be presented as HSUV decrement values, adjusted according to social demographics and comorbidities. Adjusted HSUV decrements were extracted and compiled according to individual complications. After which, subsequently grouped into mild or severe category for comparison. RESULTS: Searches identified 35 studies. The size of the study population ranged from 160 to 14,826. The HSUV decrement range was widest for cerebrovascular disease (stroke): -0.0060 to -0.0780 for mild stroke and -0.035 to -0.266 for severe stroke; retinopathy: mild (-0.005 to -0.0862), moderate (-0.0030 to -0.1845) and severe retinopathy (-0.023 to -0.2434); amputation: (-0.1050 to -0.2880). Different nature of complication severity defined in studies could be categorized into: those with acute nature, chronic with lasting effects, those with symptoms at early stage or those with repetitive frequency or episodes. DISCUSSION: Overview of HSUV decrement ranges across different stages of each T2DM diabetes-related complications shows that chronic complications with lasting impact such as amputation, severe stroke with sequelae and severe retinopathy with blindness were generally associated with larger HSUV decrement range. Considerable heterogeneities exist across the studies. Promoting standardized complication definitions and identifying the most influential health state stages on HSUV decrements may assist researchers for future cost-effectiveness studies.

Optic nerve head factors associated with initial central visual field defect in primary open-angle glaucoma.

We investigated optic nerve head factors associated with initial parafoveal scotoma (IPFS) in primary open-angle glaucoma. Eighty (80) patients with an IPFS and 84 patients with an initial nasal step (INS) were compared. Central retinal vascular trunk (CRVT) deviation from the Bruch's membrane opening (BMO) center was measured as a surrogate of lamina cribrosa (LC)/BMO offset, and its obliqueness was defined as the absolute value of angular deviation from the fovea-BMO axis. Proximity of retinal nerve fiber layer defect (RNFLD) was defined as the angular deviation of the inner RNFLD margin from the fovea-BMO axis. Microvasculature dropout (MvD) was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. Factors associated with IPFS, as compared with INS, were assessed using logistic regression analyses and conditional inference tree analysis. The IPFS group had more oblique CRVT offset (P < 0.001), RNFLD closer to the fovea (P < 0.001), more MvD (P < 0.001), and more LC defects (P < 0.001) compared to the INS group. In logistic regression analyses, obliqueness of CRVT offset (P = 0.002), RNFLD proximity (P < 0.001), and MvD (P = 0.001) were significant factors influencing the presence of IPFS. Conditional inference tree analysis showed that RNFLD closer to the fovea (P < 0.001) in the upper level, more oblique CRVT offset (P = 0.013) and presence of MvD (P = 0.001) in the lower level were associated with the probability of having IPFS. IPFS was associated with closer RNFLD location to the fovea when assessed from the BMO. Oblique LC/BMO offset may not only mask RNFLD proximity to the fovea due to a deviated funduscopic disc appearance, but also potentiate IPFS via focal LC defect and MvD.

Smart Nanocarriers for the Treatment of Retinal Diseases.

Retinal diseases, such as age-related macular degeneration, diabetic retinopathy, and retinoblastoma, stand as the leading causes of irreversible vision impairment and blindness worldwide. Effectively administering drugs for retinal diseases poses a formidable challenge due to the presence of complex ocular barriers and elimination mechanisms. Over time, various approaches have been developed to fabricate drug delivery systems for improving retinal therapy including virus vectors, lipid nanoparticles, and polymers. However, conventional nanocarriers encounter issues related to the controllability, efficiency, and safety in the retina. Therefore, the development of smart nanocarriers for effective or more invasive long-term treatment remains a desirable goal. Recently, approaches have surfaced for the intelligent design of nanocarriers, leveraging specific responses to external or internal triggers and enabling multiple functions for retinal therapy such as topical administration, prolonged drug release, and site-specific drug delivery. This Review provides an overview of prevalent retinal pathologies and related pharmacotherapies to enhance the understanding of retinal diseases. It also surveys recent developments and strategies employed in the intelligent design of nanocarriers for retinal disease. Finally, the challenges of smart nanocarriers in potential clinical retinal therapeutic applications are discussed to inspire the next generation of smart nanocarriers.

Options for Topical Treatment of Oxidative Eye Diseases with a Special Focus on Retinopathies.

Antioxidants, usually administered orally through the systemic route, are known to counteract the harmful effects of oxidative stress on retinal cells. The formulation of these antioxidants as eye drops might offer a new option in the treatment of oxidative retinopathies. In this review, we will focus on the use of some of the most potent antioxidants in treating retinal neuropathies. Melatonin, known for its neuroprotective qualities, may mitigate oxidative damage in the retina. N-acetyl-cysteine (NAC), a precursor to glutathione, enhances the endogenous antioxidant defense system, potentially reducing retinal oxidative stress. Idebenone, a synthetic analogue of coenzyme Q10, and edaravone, a free radical scavenger, contribute to cellular protection against oxidative injury. Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea, possesses anti-inflammatory and antioxidant effects that could be beneficial in cases of retinopathy. Formulating these antioxidants as eye drops presents a localized and targeted delivery method, ensuring effective concentrations reach the retina. This approach might minimize systemic side effects and enhance therapeutic efficacy. In this paper, we also introduce a relatively new strategy: the alkylation of two antioxidants, namely, edaravone and EGCG, to improve their insertion into the lipid bilayer of liposomes or even directly into cellular membranes, facilitating their crossing of epithelial barriers and targeting the posterior segment of the eye. The synergistic action of these antioxidants may offer a multifaceted defense against oxidative damage, holding potential for the treatment and management of oxidative retinopathies. Further research and clinical trials will be necessary to validate the safety and efficacy of these formulations, but the prospect of antioxidant-based eye drops represents a promising avenue for future ocular therapies.

Investigating the Impact of Dimer Interface Mutations on Norrin's Secretion and Norrin/ß-Catenin Pathway Activation.

Purpose: This study aimed to investigate the impact of 21 NDP mutations located at the dimer interface, focusing on their potential effects on protein assembly, secretion efficiency, and activation of the Norrin/ß-catenin signaling pathway. Methods: The expression level, secretion efficiency, and protein assembly of mutations were analyzed using Western blot. The Norrin/ß-catenin signaling pathway activation ability after overexpression of mutants or supernatant incubation of mutant proteins was tested in HEK293STF cells. The mutant norrin and wild-type (WT) FZD4 were overexpressed in HeLa cells to observe their co-localization. Immunofluorescence staining was conducted in HeLa cells to analyze the subcellular localization of Norrin and the Retention Using Selective Hook (RUSH) assay was used to dynamically observe the secretion process of WT and mutant Norrin. Results: Four mutants (A63S, E66K, H68P, and L103Q) exhibited no significant differences from WT in all evaluations. The other 17 mutants presented abnormalities, including inadequate protein assembly, reduced secretion, inability to bind to FZD4 on the cell membrane, and decreased capacity to activate Norrin/ß-catenin signaling pathway. The RUSH assay revealed the delay in endoplasmic reticulum (ER) exit and impairment of Golgi transport. Conclusions: Mutations at the Norrin dimer interface may lead to abnormal protein assembly, inability to bind to FZD4, and decreased secretion, thus contributing to compromised Norrin/ß-catenin signaling. Our results shed light on the pathogenic mechanisms behind a significant proportion of NDP gene mutations in familial exudative vitreoretinopathy (FEVR) or Norrie disease.

Tandem Mass Tag LC-MS/MS of Aqueous Humor From Individuals With Type 2 Diabetes Without Retinopathy Reveals Early Dysregulation of Synaptic Proteins.

Purpose: An early neurodegenerative component of diabetic retinal disease (DRD) that precedes the vascular findings of clinically diagnosed diabetic retinopathy (DR) is increasingly being recognized. However, the relevant molecular mechanisms and biomarkers for early DRD are poorly defined. The purpose of this study was to uncover novel potential mediators of early diabetic retinal neuronal dysfunction through analysis of the aqueous fluid proteome in preclinical DR. Methods: Aqueous fluid was collected from subjects with type 2 diabetes mellitus (DM) but no clinical DR and from nondiabetic controls undergoing routine cataract surgery. Preoperative spectral-domain optical coherence tomography of the macula was obtained. Tandem mass tag LC-MS/MS was performed to identify proteins differentially present in diabetic and control aqueous fluid, and proteins with >50% change and P < 0.05 were considered significant. Selected results were validated with western blot of human aqueous fluid samples. Results: We identified decreased levels of proteins implicated in neuronal synapse formation and increased levels of inflammatory proteins in the aqueous fluid from patients with type 2 DM but no DR compared with controls. Of the differentially present synaptic proteins that we identified and confirmed with western blot, the majority have not previously been linked with DRD. Conclusions: The proteomic profile of aqueous fluid from individuals with type 2 DM but no DR suggests that retinal neuronal dysfunction and inflammation represent very early events in the pathophysiology of DRD. These findings support the concept that diabetic retinal neurodegeneration precedes vascular pathology and reveal novel potential mediators and/or biomarkers warranting further investigation.

Long-term outcomes of anti-vascular endothelial growth factor therapy with and without posterior scleral reinforcement on myopic maculopathy in myopic choroidal neovascularization eyes.

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is used for myopic choroidal neovascularization (mCNV). Patchy chorioretinal atrophy (pCRA) enlargement has been reported in mCNV cases associated with vision loss. Our aim was to compare the long-term effectiveness of anti-VEGF therapy alone versus anti-VEGF followed by posterior scleral reinforcement (PSR) in controlling myopic maculopathy in mCNV eyes. METHODS: We performed a retrospective review of the medical records of 95 high myopia patients (refractive error ≥ 6.00 diopters, axial length ≥ 26.0 mm) with mCNV. Patients were treated with anti-VEGF alone (group A) or anti-VEGF followed by PSR (group B). The following data were collected: refractive error, best corrected visual acuity (BCVA), ophthalmic fundus examination, ocular coherence tomography and ocular biometry at 12 and 24 months pre- and postoperatively. The primary outcomes were changes in pCRA and BCVA. RESULTS: In 26 eyes of 24 patients, the mean pCRA size significantly increased from baseline (0.88 ± 1.69 mm2) to 12 months (1.57 ± 2.32 mm2, t = 3.249, P = 0.003) and 24 months (2.17 ± 2.79 mm2, t = 3.965, P = 0.001) postoperatively. The increase in perilesional pCRA in group B (n = 12) was 98.2% and 94.2% smaller than that in group A (n = 14) at 12 and 24 months (Beta 0.57 [95% CI 0.01, 191 1.13], P = 0.048). In group B, 7 eyes (58.3%) gained more than 2 lines of BCVA compared with only 4 eyes (28.6%) in group A at 24 months. CONCLUSION: Anti-VEGF therapy followed by PSR achieved better outcomes than anti-VEGF therapy alone in controlling the development of myopic maculopathy in mCNV and may constitute a better treatment option by securing a better long-term VA outcome.

Paraneoplastic vision loss.

Paraneoplastic vision loss, which represents a small percentage of paraneoplastic neurologic syndromes, can be a blinding disease. Presenting visual symptoms are variable, making diagnosis challenging. History of the presenting illness, ocular examination, and utilization of various modalities, such as automated perimetry, ocular coherence tomography, and electroretinogram allow for localization of vision loss to the optic nerves or retina, guiding in diagnosis and management. Paraneoplastic vision loss is often painless, bilateral, and subacute, and accompanies other neurologic symptoms but can be the first presenting symptom. Paraneoplastic optic neuropathy has been described in association with several antibodies, but most commonly anti-CRMP5. Cancer-associated retinopathy is the most common paraneoplastic autoimmune retinopathy; however, melanoma-associated retinopathy and bilateral diffuse uveal melanocytic proliferation have also been described to be associated with a paraneoplastic process affecting the retina. Paraneoplastic visual loss is an expanding field and advances in research have improved phenotypic characterization; however, further work is needed to identify more reliable biomarkers of disease and to better understand the underlying mechanisms and management.